TJTES 2020-4 by KAREPUBLISHING

ISSN 1306 - 696X

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi

Volume 26 | Number 4 | July 2020

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Mehmet Kurtoğlu Editors M. Mahir Özmen Mehmet Eryılmaz Publication Coordinator Mehmet Eryılmaz Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu, Recep Güloğlu Section Editors Anaesthesiology & ICU Güniz Meyancı Köksal, Mert Şentürk Cardiac Surgery Münacettin Ceviz, Murat Güvener Neurosurgery Ahmet Deniz Belen, Mehmet Yaşar Kaynar Ophtalmology Cem Mocan, Ali Hakan Durukan Ortopedics and Traumatology Mahmut Nedim Doral, Ali Erşen Plastic and Reconstructive Surgery Figen Özgür, Atakan Aydın Pediatric Surgery Aydın Yağmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu Emergency Medicine Burak Katipoğlu, Bülent Erbil Gynecology and Obstetrics Recep Has, Kazım Emre Karaşahin

www.tjtes.org

THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ President (Başkan) Vice President (2. Başkan) Secretary General (Genel Sekreter) Treasurer (Sayman) Members (Yönetim Kurulu Üyeleri)

Orhan Alimoğlu Mehmet Eryılmaz Ali Fuat Kaan Gök Gökhan Akbulut Osman Şimşek Münevver Moran Adnan Özpek

ISSUED BY THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ YAYIN ORGANI Owner (Ulusal Travma ve Acil Cerrahi Derneği adına Sahibi) Editorial Director (Yazı İşleri Müdürü) Managing Editor (Yayın Koordinatörü) Publication Secretary (Yayın Sekreteri) Emblem (Amblem) Correspondence address (Yazışma adresi) Tel Fax (Faks)

Orhan Alimoğlu Orhan Alimoğlu M. Mahir Özmen Kerem Ayar Metin Ertem Ulusal Travma ve Acil Cerrahi Dergisi Sekreterliği Şehremini Mah., Köprülü Mehmet Paşa Sok., Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul +90 212 - 531 12 46 - 588 62 46 +90 212 - 586 18 04

p-ISSN 1306-696x • e-ISSN 1307-7945 • Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), DOAJ, EBSCO ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır.) Publisher (Yayımcı): KARE Yayıncılık (KARE Publishing) • www.kareyayincilik.com • Design (Tasarım): Ali Cangül • Graphics (Grafikler): Edibe Çomaktekin • Linguistic Editor (İngilizce Editörü): Suzan Atwood • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): July (Temmuz) 2020 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE P U B L I S H I N G

www.tjtes.org

INFORMATION FOR THE AUTHORS The Turkish Journal of Trauma and Emergency Surgery (TJTES) is an official publication of the Turkish Association of Trauma and Emergency Surgery. It is a peer-reviewed periodical that considers for publication clinical and experimental studies, case reports, technical contributions, and letters to the editor. Six issues are published annually.

manuscript title, author names and institutions and correspondence address, abstract in Turkish (for Turkish authors only), and title and abstract in English are uploaded to the Journal Agent system in the relevant steps. The main text includes Introduction, Materials and Methods, Results, Discussion, Acknowledgments, References, Tables and Figure Legends.

As from 2001, the journal is indexed in Index Medicus and Medline, as from 2005 in Excerpta Medica and EMBASE, as from 2007 in Science Citation Index Expanded (SCI-E) and Journal Citation Reports / Science Edition, and as from 2014 in EBSCOhost. Our impact factor in SCI-E indexed journals is 0.643 (JCR 2019). It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PubMed.

The cover letter must contain a brief statement that the manuscript has been read and approved by all authors, that it has not been submitted to, or is not under consideration for publication in, another journal. It should contain the names and signatures of all authors. The cover letter is uploaded at the 10th step of the “Submit New Manuscript” section, called “Upload Your Files”.

Submission of a manuscript by electronic means implies: that the work has not been published before (except in the form of an abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; and that its publication in the Turkish Journal of Trauma and Emergency Surgery is approved by all co-authors. The author(s) transfer(s) the copyright to the Turkish Association of Trauma and Emergency Surgery to be effective if and when the manuscript is accepted for publication. The author(s) guarantee(s) that the manuscript will not be published elsewhere in any other language without the consent of the Association. If the manuscript has been presented at a meeting, this should be stated together with the name of the meeting, date, and the place.

Abstract: The abstract should be structured and serve as an informative guide for the methods and results sections of the study. It must be prepared with the following subtitles: Background, Methods, Results and Conclusions. Abstracts should not exceed 200 words.

Manuscripts must be submitted in English. All submissions are initially reviewed by the editor, and then are sent to reviewers. All manuscripts are subject to editing and, if necessary, will be returned to the authors for answered responses to outstanding questions or for addition of any missing information to be added. For accuracy and clarity, a detailed manuscript editing is undertaken for all manuscripts accepted for publication. Final galley proofs are sent to the authors for approval. Unless specifically indicated otherwise at the time of submission, rejected manuscripts will not be returned to the authors, including accompanying materials. TJTES is indexed in Science Citation Index-Expanded (SCI-E), Index Medicus, Medline, EMBASE, Excerpta Medica, and the Turkish Medical Index of TUBITAK-ULAKBIM. Priority of publications is given to original studies; therefore, selection criteria are more refined for reviews and case reports. Submission Fee: In order to further improve the quality and accessibility of the journal, a fee will be charged as a contribution to the cost of production. This fee will be charged during the process of application of submitted articles and will be charged regardless of eventual acceptance/rejection of the manuscript. Foreign authors can complete the article submission process after depositing USD 100.- to the USD account below. The article number released at the last stage of the article upload process must be written in the bank shipment description section. Recipient: ULUSAL TRAVMA VE ACIL CERRAHI DERNEGI IKTISADI ISLETMESI IBAN: TR02 0006 4000 0021 0490 9277 35 (USD) Turkish authors can complete the article submission process after depositing 500.- TL to the account below. The article number released at the last stage of the article upload process must be written in the bank shipment description section. Alıcı: ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ İKTİSADİ İŞLETMESİ IBAN: TR37 0006 4000 0021 0491 5103 66 (Türk Lirası Hesabı) Open Access Policy: Full text access is free. There is no charge for downloading the full text of printed material. Manuscript submission: TJTES accepts only on-line submission via the official web site (please click, www.travma.org.tr/en) and refuses printed manuscript submissions by mail. All submissions are made by the on-line submission system called Journal Agent, by clicking the icon “Online manuscript submission” at the above mentioned web site homepage. The system includes directions at each step but for further information you may visit the web site (http://www.travma.org/en/journal/). Manuscript preparation: Manuscripts should have double-line spacing, leaving sufficient margin on both sides. The font size (12 points) and style (Times New Roman) of the main text should be uniformly taken into account. All pages of the main text should be numbered consecutively. Cover letter,

Figures, illustrations and tables: All figures and tables should be numbered in the order of appearance in the text. The desired position of figures and tables should be indicated in the text. Legends should be included in the relevant part of the main text and those for photomicrographs and slide preparations should indicate the magnification and the stain used. Color pictures and figures will be published if they are definitely required and with the understanding that the authors are prepared to bear the costs. Line drawings should be professionally prepared. For recognizable photographs, signed releases of the patient or of his/her legal representatives should be enclosed; otherwise, patient names or eyes must be blocked out to prevent identification. References: All references should be numbered in the order of mention in the text. All reference figures in the text should be given in brackets without changing the font size. References should only include articles that have been published or accepted for publication. Reference format should conform to the “Uniform requirements for manuscripts submitted to biomedical journals” (http://www.icmje.org) and its updated versions (February 2006). Journal titles should be abbreviated according to Index Medicus. Journal references should provide inclusive page numbers. All authors, if six or fewer, should be listed; otherwise the first six should be listed, followed by “et al.” should be written. The style and punctuation of the references should follow the formats below: Journal article: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5. Chapter in book: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62. Our journal has succeeded in being included in several indexes, in this context, we have included a search engine in our web site (www.travma.org.tr) so that you can access full-text articles of the previous issues and cite the published articles in your studies. Review articles: Only reviews written by distinguished authors based on the editor’s invitation will be considered and evaluated. Review articles must include the title, summary, text, and references sections. Any accompanying tables, graphics, and figures should be prepared as mentioned above. Case reports: A limited number of case reports are published in each issue of the journal. The presented case(s) should be educative and of interest to the readers, and should reflect an exclusive rarity. Case reports should contain the title, summary, and the case, discussion, and references sections. These reports may consist of maximum five authors. Letters to the Editor: “Letters to the Editor” are only published electronically and they do not appear in the printed version of TJTES and PUBMED. The editors do not issue an acceptance document as an original article for the ‘’letters to the editor. The letters should not exceed 500 words. The letter must clearly list the title, authors, publication date, issue number, and inclusive page numbers of the publication for which opinions are released. Informed consent - Ethics: Manuscripts reporting the results of experimental studies on human subjects must include a statement that informed consent was obtained after the nature of the procedure(s) had been fully explained. Manuscripts describing investigations in animals must clearly indicate the steps taken to eliminate pain and suffering. Authors are advised to comply with internationally accepted guidelines, stating such compliance in their manuscripts and to include the approval by the local institutional human research committee.

YAZARLARA BİLGİ Ulusal Travma ve Acil Cerrahi Dergisi, Ulusal Travma ve Acil Cerrahi Derneği’nin yayın organıdır. Travma ve acil cerrahi hastalıklar konularında bilimsel birikime katkısı olan klinik ve deneysel çalışmaları, editöryel yazıları, klinik olgu sunumlarını ve bu konulardaki teknik katkılar ile son gelişmeleri yayınlar. Dergi iki ayda bir yayınlanır. Ulusal Travma ve Acil Cerrahi Dergisi TÜBİTAK TR Dizinde taranmaktadır, ayrıca uluslararası indekslerde, 2001 yılından itibaren Index Medicus, PubMed’de, 2005 yılından itibaren EMBASE’de, 2007 yılından itibaren Web of Science, Science Citation Index-Expanded’de (SCI-E), 2014 yılından itibaren de EBSCOhost indeksinde dizinlenmektedir. 2018 Journal Citation Report IF puanımız 0.643 olmuştur. Dergide araştırma yazılarına öncelik verilmekte, bu nedenle derleme veya olgu sunumu türündeki yazılarda seçim ölçütleri daha dar tutulmaktadır. PUBMED’de dergi “Ulus Travma Acil Cerrahi Derg” kısaltması ile yer almaktadır. Dergiye yazı teslimi, çalışmanın daha önce yayınlanmadığı (özet ya da bir sunu, inceleme, ya da tezin bir parçası şeklinde yayınlanması dışında), başka bir yerde yayınlanmasının düşünülmediği ve Ulusal Travma ve Acil Cerrahi Dergisi’nde yayınlanmasının tüm yazarlar tarafından uygun bulunduğu anlamına gelmektedir. Yazar(lar), çalışmanın yayınlanmasının kabulünden başlayarak, yazıya ait her hakkı Ulusal Travma ve Acil Cerrahi Derneği’ne devretmektedir(ler). Yazar(lar), izin almaksızın çalışmayı başka bir dilde ya da yerde yayınlamayacaklarını kabul eder(ler). Gönderilen yazı daha önce herhangi bir toplantıda sunulmuş ise, toplantı adı, tarihi ve düzenlendiği şehir belirtilmelidir. Dergide İngilizce yazılmış makaleler yayınlanır. Tüm yazılar önce editör tarafından ön değerlendirmeye alınır; daha sonra incelenmesi için danışma kurulu üyelerine gönderilir. Tüm yazılarda editöryel değerlendirme ve düzeltmeye başvurulur; gerektiğinde, yazarlardan bazı soruları yanıtlanması ve eksikleri tamamlanması istenebilir. Dergide yayınlanmasına karar verilen yazılar “manuscript editing” sürecine alınır; bu aşamada tüm bilgilerin doğruluğu için ayrıntılı kontrol ve denetimden geçirilir; yayın öncesi şekline getirilerek yazarların kontrolüne ve onayına sunulur. Editörün, kabul edilmeyen yazıların bütününü ya da bir bölümünü (tablo, resim, vs.) iade etme zorunluluğu yoktur. Makale Gönderim Ücreti (Submission Fee): Dergimizin maliyetine katkı olarak, gönderilen makalelerde “başvurusu sırasında; kabul/red şartına bağlı olmaksızın” ücretlendirme yapılacaktır. Türk yazarlar aşağıdaki hesaba 500.- TL yatırdıktan sonra makale gönderim işlemini tamamlayabilirler. Alıcı: Ulusal Travma ve Acil Cerrahi Derneği IBAN: TR37 0006 4000 0021 0491 5103 66 (T. İş Bankası) (Banka gönderisi açıklama kısmına, makale yükleme işlemi sırasında son aşamadaki çıkacak makale numarası mutlaka yazılmalıdır). Açık Erişim İlkesi: Tam metinlere erişim ücretsizdir. Yayınlanan basılı materyali tam metni indirmek için herhangi bir ücret alınmaz. Yazıların hazırlanması: Tüm yazılı metinler 12 punto büyüklükte “Times New Roman” yazı karakterinde iki satır aralıklı olarak yazılmalıdır. Sayfada her iki tarafta uygun miktarda boşluk bırakılmalı ve ana metindeki sayfalar numaralandırılmalıdır. Journal Agent sisteminde, başvuru mektubu, başlık, yazarlar ve kurumları, iletişim adresi, Türkçe özet ve yazının İngilizce başlığı ve özeti ilgili aşamalarda yüklenecektir. İngilizce yazılan çalışmalara da Türkçe özet eklenmesi gerekmektedir. Yazının ana metnindeyse şu sıra kullanılacaktır: Giriş, Gereç ve Yöntem, Bulgular, Tartışma, Teşekkür, Kaynaklar, Tablolar ve Şekiller. Başvuru mektubu: Bu mektupta yazının tüm yazarlar tarafından okunduğu, onaylandığı ve orijinal bir çalışma ürünü olduğu ifade edilmeli ve yazar isimlerinin yanında imzaları bulunmalıdır. Başvuru mektubu ayrı bir dosya olarak, Journal Agent sisteminin “Yeni Makale Gönder” bölümünde, 10. aşamada yer alan dosya yükleme aşamasında yollanmalıdır. Başlık sayfası: Yazının başlığı, yazarların adı, soyadı ve ünvanları, çalışmanın yapıldığı kurumun adı ve şehri, eğer varsa çalışmayı destekleyen fon ve kuruluşların açık adları bu sayfada yer almalıdır. Bu sayfaya ayrıca “yazışmadan sorumlu” yazarın isim, açık adres, telefon, faks, mobil telefon ve e-posta bilgileri eklenmelidir. Özet: Çalışmanın gereç ve yöntemini ve bulgularını tanıtıcı olmalıdır. Türkçe özet, Amaç, Gereç ve Yöntem, Bulgular, Sonuç ve Anahtar Sözcükler başlıklarını; İngilizce özet Background, Methods, Results, Conclusion ve Key words başlıklarını içermelidir. İngilizce olarak hazırlanan çalışmalarda da Türkçe özet yer almalıdır. Özetler başlıklar hariç 190210 sözcük olmalıdır.

Tablo, şekil, grafik ve resimler: Şekillere ait numara ve açıklayıcı bilgiler ana metinde ilgili bölüme yazılmalıdır. Mikroskobik şekillerde resmi açıklayıcı bilgilere ek olarak, büyütme oranı ve kullanılan boyama tekniği de belirtilmelidir. Yazarlara ait olmayan, başka kaynaklarca daha önce yayınlanmış tüm resim, şekil ve tablolar için yayın hakkına sahip kişilerden izin alınmalı ve izin belgesi dergi editörlüğüne ayrıca açıklamasıyla birlikte gönderilmelidir. Hastaların görüntülendiği fotoğraflara, hastanın ve/veya velisinin imzaladığı bir izin belgesi eşlik etmeli veya fotoğrafta hastanın yüzü tanınmayacak şekilde kapatılmış olmalıdır. Renkli resim ve şekillerin basımı için karar hakemler ve editöre aittir. Yazarlar renkli baskının hazırlık aşamasındaki tutarını ödemeyi kabul etmelidirler. Kaynaklar: Metin içindeki kullanım sırasına göre düzenlenmelidir. Makale içinde geçen kaynak numaraları köşeli parantezle ve küçültülmeden belirtilmelidir. Kaynak listesinde yalnızca yayınlanmış ya da yayınlanması kabul edilmiş çalışmalar yer almalıdır. Kaynak bildirme “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (http:// www.icmje.org) adlı kılavuzun en son güncellenmiş şekline (Şubat 2006) uymalıdır. Dergi adları Index Medicus’a uygun şekilde kısaltılmalıdır. Altı ya da daha az sayıda olduğunda tüm yazar adları verilmeli, daha çok yazar durumunda altıncı yazarın arkasından “et al.” ya da “ve ark.” eklenmelidir. Kaynakların dizilme şekli ve noktalamalar aşağıdaki örneklere uygun olmalıdır: Dergi metni için örnek: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5. Kitaptan bölüm için örnek: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62. Sizlerin çalışmalarınızda kaynak olarak yararlanabilmeniz için www.travma.org.tr adresli web sayfamızda eski yayınlara tam metin olarak ulaşabileceğiniz bir arama motoru vardır. Derleme yazıları: Bu tür makaleler editörler kurulu tarafından gerek olduğunda, konu hakkında birikimi olan ve bu birikimi literatüre de yansımış kişilerden talep edilecek ve dergi yazım kurallarına uygunluğu saptandıktan sonra değerlendirmeye alınacaktır. Derleme makaleleri; başlık, Türkçe özet, İngilizce başlık ve özet, alt başlıklarla bölümlendirilmiş metin ile kaynakları içermelidir. Tablo, şekil, grafik veya resim varsa yukarıda belirtildiği şekilde gönderilmelidir. Olgu sunumları: Derginin her sayısında sınırlı sayıda olgu sunumuna yer verilmektedir. Olgu bildirilerinin kabulünde, az görülürlük, eğitici olma, ilginç olma önemli ölçüt değerlerdir. Ayrıca bu tür yazıların olabildiğince kısa hazırlanması gerekir. Olgu sunumları başlık, Türkçe özet, İngilizce başlık ve özet, olgu sunumu, tartışma ve kaynaklar bölümlerinden oluşmalıdır. Bu tür çalışmalarda en fazla 5 yazara yer verilmesine özen gösterilmelidir. Editöre mektuplar: Editöre mektuplar basılı dergide ve PUBMED’de yer almamakta, ancak derginin web sitesinde yayınlanmaktadır. Bu mektuplar için dergi yönetimi tarafından yayın belgesi verilmemektedir. Daha önce basılmış yazılarla ilgili görüş, katkı, eleştiriler ya da farklı bir konu üzerindeki deneyim ve düşünceler için editöre mektup yazılabilir. Bu tür yazılar 500 sözcüğü geçmemeli ve tıbbi etik kurallara uygun olarak kaleme alınmış olmalıdır. Mektup basılmış bir yazı hakkında ise, söz konusu yayına ait yıl, sayı, sayfa numaraları, yazı başlığı ve yazarların adları belirtilmelidir. Mektup bir konuda deneyim, düşünce hakkında ise verilen bilgiler doğrultusunda dergi kurallarına uyumlu olarak kaynaklar da belirtilmelidir. Bilgilendirerek onay alma - Etik: Deneysel çalışmaların sonuçlarını bildiren yazılarda, çalışmanın yapıldığı gönüllü ya da hastalara uygulanacak prosedür(lerin) özelliği tümüyle anlatıldıktan sonra, onaylarının alındığını gösterir bir cümle bulunmalıdır. Yazarlar, bu tür bir çalışma söz konusu olduğunda, uluslararası alanda kabul edilen kılavuzlara ve T.C. Sağlık Bakanlığı tarafından getirilen yönetmelik ve yazılarda belirtilen hükümlere uyulduğunu belirtmeli ve kurumdan aldıkları Etik Komitesi onayını göndermelidir. Hayvanlar üzerinde yapılan çalışmalarda ağrı, acı ve rahatsızlık verilmemesi için neler yapıldığı açık bir şekilde belirtilmelidir. Yazı gönderme - Yazıların gönderilmesi: Ulusal Travma ve Acil Cerrahi Dergisi yalnızca www.travma.org.tr adresindeki internet sitesinden on-line olarak gönderilen yazıları kabul etmekte, posta yoluyla yollanan yazıları değerlendirmeye almamaktadır. Tüm yazılar ilgili adresteki “Online Makale Gönderme” ikonuna tıklandığında ulaşılan Journal Agent sisteminden yollanmaktadır. Sistem her aşamada kullanıcıyı bilgilendiren özelliktedir.

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 26

Number - Sayı 4 July - Temmuz 2020

Contents - İçindekiler Experimental Studies - Deneysel Çalışma 497-502 Assessment of plasma and tissue fibronectin EIIIB splice variant expressions measured serially using RT-PCR in a wound model of rabbits Tavşan yara modelinde RT-PCR yöntemi ile seri olarak ölçülen plazma ve doku fibronektin EIIIB splice değerlerinin ölçümleri Kurt Özkaya N, Zereyak U, Açıkalın Coşkun K, Tutar Y, Yılmaz S 503-508 Effects of garlic oil (allium sativum) on acetic acid-induced colitis in rats: Garlic oil and experimental colitis Sıçanlarda asetik asitle indüklenen kolit üzerine sarımsak yağının etkileri: Sarımsak yağı ve deneysel kolit Tanrikulu Y, Şen Tanrıkulu C, Kılınç F, Can M, Köktürk F 509-516 Effects of sugammadex on ischemia reperfusion in a rat extremity model Sıçan ekstremite modelinde iskemi reperfüzyon üzerine sugammadeks’in etkisi Alagöz A, Küçükgüçlü S, Boztaş N, Hancı V, Yuluğ E, Şişman AR 517-525 The effects of specific and non-specific phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress and remote organ injury in two-hit trauma model İki darbe modelinde spesifik ve non-spesifik fosfodiesteraz inhibitörleri ve N-asetilsisteinin oksidatif stres ve uzak organ hasarına etkisi Özer Ö, Topal U, Şen M

Original Articles - Orijinal Çalışma 526-530 Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in blunt chest trauma patients Künt göğüs travması hastalarında Tp-e aralığı, Tp-e/QT oranı ve Tp-e/QTc oranının değerlendirilmesi Çaltekin İ, Hidayet Ş 531-537 The effects of analgesic treatment and chest physiotherapy on the complications of the patients with rib fractures that arise from blunt chest trauma Künt toraks travması sonucu izole kot fraktürü gelişen hastalarda analjezik tedavi ve solunum fizyoterapisinin komplikasyonlara etkisi Alar T, Gedik İE, Kara M 538-544 Comparison of post-operative outcomes of graft materials used in reconstruction of blow-out fractures Blow-out fraktürleri onarımında kullanılan greft materyallerinin ameliyat sonrası sonuçlarının karşılaştırılması Düzgün S, Kayahan Sirkeci B 545-554 Professional practice assessment for minor head injury management in emergency department and clinical impact of a simulation-based training: Interventional study (before/after) Acil serviste hafif kafa travması yönetimi için profesyonel uygulamanın değerlendirilmesi ve simülasyon tabanlı eğitimin klinik etkisi: Girişimsel çalışma “öncesi-sonrası” Vandingenen P, Chauvin A, Javaud N, Ghazali DA 555-562 Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy Apendektomi yapılan gebe ve gebe olmayan hastaların demografik ve klinik özelliklerinin karşılaştırılması Koç C, Akbulut S, Coşkun Eİ, Sarıcı B, Yılmaz S 563-567 An investigation into the effects of hemodynamic changes on the patient’s clinical condition during the treatment of patients undergoing aneurysmal subarachnoid hemorrhage Anevrizmal subaraknoid kanama geçiren hastalarda tedavi süresince gelişen hemodinamik değişikliklerin kliniğe etkilerinin araştırılması Yaman Mammadov N, Ali A, Mammadov O, Jima AK, Orhun G, Akıncı İÖ 568-573 Blood-aqueous barrier deterioration following retained metallic corneal foreign body: A laser flare photometric study Lazer flare fotometri ile korneal yabancı cisim sonrası kan-aköz bariyerinde bozulmanın gösterilmesi Onur İU, Zırtıloğlu S, Sonbahar O, Çavuşoğlu E, Yiğit U 574-579 How important is susceptibility-weighted imaging in mild traumatic brain injury? Hafif travmatik beyin hasarında duyarlılık ağırlıklı görüntüleme ne kadar önemli? Eldeş T, Beyazal Çeliker F, Bilir Ö, Ersunan G, Yavaşi Ö, Turan A, Toprak U

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 26

Number - Sayı 4 July - Temmuz 2020

Contents - İçindekiler 580-585 Can the C-reactive protein-to-plasma albumin ratio be an alternative scoring to show mortality and morbidity in patients with colorectal cancer? Kolorektal kanserli hastalarda C-reaktif protein ve plazma albumin seviyesinin oranı mortalite ve morbiditeyi göstermede alternatif bir skorlama olabilir mi? Şahiner Y, Yıldırım MB 586-592 In intra-articular distal humeral fractures: Can combined medial-lateral approach gain better outcomes than olecranon osteotomy? İntraartiküler distal humerus kırıklarında: Kombine mediolateral yaklaşım olekranon osteotomisinden daha iyi sonuçlar elde edilmesini sağlayabilir mi? Wei L, Xu H, An Z 593-599 The role of the lactate level in determining the risk rates of small bowel resection in incarcerated hernias İnkarsere hernilerde ince bağırsak rezeksiyonu risk oranlarını saptamada laktat düzeyinin rolü Şahin M, Buluş H, Yavuz A, Turhan VB, Öztürk B, Kılıç NA, Babayiğit M, Öztürk D 600-606 Perioperative outcomes following a hip fracture surgery in elderly patients with heart failure with preserved ejection fraction and heart failure with a mid-range ejection fraction Korunmuş ejeksiyon fraksiyonu ile kalp yetersizlikli ve sınırda ejeksiyon fraksiyonu ile kalp yetersizlikli yaşlı hastalarda kalça kırığı cerrahisi sonrası perioperatif sonuçlar Açan AE, Özlek B, Kılınç CY, Biteker M, Aydoğan NH 607-612 Is the preoperative neutrophil-to-lymphocyte ratio a predictive value for postoperative mortality in orthogeriatric patients who underwent proximal femoral nail surgery for pertrochanteric fractures? Ameliyat öncesi nötrofil-lenfosit oranı pertrokanterik kırık nedeniyle proksimal femoral çivi planlanan ortogeriatrik popülasyon için ameliyat sonrası mortaliteyi belirlemede kullanılabilecek ameliyat öncesi bir değer midir? Özbek EA, Ayanoğlu T, Olçar HA, Yalvaç ES 613-619 Assessment of computed tomography indications and computed tomography reports for usefulness in clinical presentation at postoperative follow-up of gunshot wound cases Ateşli silah yaralanması olgularının ameliyat sonrası takibinde bilgisayarlı tomografi endikasyonları ve bilgisayarlı tomografi raporlarının kliniğe yararlılığı açısından değerlendirilmesi Üstüner MA, Eryılmaz M 620-627 Effects of catheter orifice configuration (triple-hole versus end-hole) in continuous infraclavicular brachial plexus block on analgesia after upper limb surgery Sürekli infraklaviküler brakial pleksus bloğunda kateter ucu konfigürasyonunun (üç delikliye karşı uçtan delikli) üst ekstremite cerrahisi sonrası analjeziye etkisi Eskin MB, Ceylan A

Case Reports - Olgu Sunumu 628-631 Acute spinal epidural hematoma: A case report and review of the literature Akut spinal epidural hematom: Olgu sunumu ve literatürün gözden geçirilmesi Akar E, Öğrenci A, Koban O, Yılmaz M, Dalbayrak S 632-634 A rarely encountered case: A neuroendocrine tumor in strangulated Littre’s hernia Nadir görülen bir olgu: Strangüle Littre hernisi içerisinde nöroendokrin tümör Erdoğan A, Bostanoğlu A 635-638 Failed angioembolization of a ruptured liver hemangioma complicated by iatrogenic injury of subclavian vein during catheter insertion Kateter yerleştirilmesi sırasında subklavyen venin iyatrojenik yaralanması ile komplike olan rüptüre karaciğer hemanjiyomunun başarısız anjiyoembolizasyonu Kang WS, Jo YG, Park YC 639-641 Fallopian tube herniation from trocar-site after laparoscopic appendectomy Laparoskopik apendektomi sonrası trokar yerinden fallop tüpü herniasyonu Ergin A, İşcan Y, Ağca B, Karip B, Memişoğlu K 642-646 “Step-by-step” principles of safe laparoscopic approach with technical details in “median arcuate ligament syndrome” “Median arcuate ligament sendromu”nda adım adım teknik detaylarıyla beraber güvenli laparoskopik yaklaşımın ilkeleri Gülmez S 647-649 Spontaneous direct inguinal hernia rupture and intestinal mesenteric separation: A case report Spontan rüptüre direkt inguinal herni ve intestinal mezenter ayrışması: Olgu sunumu Görgülü Ö, Koşar MN

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EXPERIMENTAL STUDY

Assessment of plasma and tissue fibronectin EIIIB splice variant expressions measured serially using RT-PCR in a wound model of rabbits Neşe Kurt Özkaya, M.D.,1 Umut Zereyak, M.D.,2 Yusuf Tutar, M.D.,4 Sarper Yılmaz, M.D.5

Kübra Açıkalın Coşkun, M.D.,3

Department of Plastic Reconstructive and Aesthetic Surgery, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

Department of Plastic Reconstructive and Aesthetic Surgery, Private Medicana Hospital, Sivas-Turkey

Research Center, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

Department of Biochemistry, Basic Pharmaceutical Sciences, University of Health Sciences Faculty of Pharmacy,

and Molecular Medicine Program, İstanbul-Turkey 5

Department of Plastic Reconstructive and Aesthetic Surgery, Ufuk University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: Fibronectin (FN) is an indispensable part of the extracellular matrix. During regeneration or wound healing, the plasma form of FN is incorporated into the fibrin clots to form a temporary fibrin-FN matrix, and also locally synthesized cellular FN migrates to the clot to regenerate the injured tissue. We aimed to examine wound tissue FN EIIIB and plasma FN EIIIB expression levels in an experimental wound healing model in rabbits. METHODS: Plasma and tissue EIIIB splice variant expressions were measured serially with RT-qPCR in a cutaneous wound model of rabbits. RESULTS: Tissue FN expression increased as beginning on day 3 and continued to increase on days 6 and 9, reaching maximum expression at day 12 before starting to decrease. On the contrary to the tissue levels, plasma FN levels gradually decreased until day 15 when expression returned to the initial values. CONCLUSION: The findings of the current study support that tissue EIIIB expression level increases during wound healing; and plasma EIIIB expression level decreases minimal changed. This is in contrast to reports where plasma FN provisionally helps ECM formation. Therefore, our data show an essential role of EIIIB at the tissue level in accelerating the wound healing process. The RT-qPCR method in our experimental setup can provide more accurate and precise results compared to the antibody-based methods. Keywords: Fibronectin; plasma fibronectin EIIIB; rabbit; RT-qPCR; wound healing.

INTRODUCTION The cutaneous wound healing process varies depending on the depth of the wound, infection status, and presence of chronic diseases that may impair skin wound healing, especially when the wound itself is found chronically. It has several consecutive biochemical steps as follows: rapid vasoconstriction and coagulation, vasodilatation and inflammation, prolif-

eration, reepithelialization, differentiation, angiogenesis, and synthesis and remodeling of extracellular matrix (ECM). The whole process can be beinated, step by step process that is directed by interactions between intracell and intercellular divided into three phases: inflammatory, proliferative, and remodeling.[1,2] This healing is a tightly coord.

Cite this article as: Kurt Özkaya N, Zereyak U, Açıkalın Coşkun K, Tutar Y, Yılmaz S. Assessment of plasma and tissue fibronectin EIIIB splice variant expressions measured serially using RT-PCR in a wound model of rabbits. Ulus Travma Acil Cerrahi Derg 2020;26:497-502. Address for correspondence: Neşe Kurt Özkaya, M.D. Sivas Cumhuriyet Üniversitesi Tıp Fakültesi Plastik Rekonstrüktif Estetik Cerrahi Anabilim Dalı, Sivas, Turkey Tel: +90 346 - 258 04 25 E-mail: ozkayanesekurt@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):497-502 DOI: 10.14744/tjtes.2020.25260 Submitted: 31.01.2020 Accepted: 28.03.2020 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Fibronectin (FN) is a glycoprotein that roles in cellular interactions and plays important functions in several processes, including cell adhesion, proliferation, migration, and differentiation.[1] FN is an omnipresent and necessary element of the ECM.[3] FN forms a dimer using its C terminal region. Each monomer arises from three types of repetitions: types I, II and III. Alternative splicing of FN may form different variants, but universally type III variants are important: Type IIIA (EIIIA located between FN repeats III11 and III12) and type IIIB (EIIIB located between FN repeats III7 and III8).[4] These variable repetitive units are one of the basic structures of the cell and are involved in different intracellular or intercellular functions, during tissue repair, and wound healing.[3] FN of plasma and tissue play differential and temporally significant functions during wound healing. Therefore, identifying a balance between the various isoforms of FN during tissue remodeling is essential to understanding the molecular basis of wound healing. At the site of tissue injury, FN binds to platelets and facilitates cell movement to the affected area. Expression of FN isoforms, EIIIA and EIIIB, is elevated to help tissue repair. However, it is unclear why plasma fibronectin (pFN) isoforms act simultaneously during wound healing. This complementary protein isoform function contradicts reports of pFN turnover to tissue fibronectin (tFN) but supports EIIIB complementation of EIIIA.[5] EIIIB expression increases at the site of the wound in the tissue to help ECM formation. Thorough literature research was performed to investigate this phenomenon and interestingly, only one study reported increased plasma EIIIB (pEIIIB) expression upon tissue injury,[6] but several reports using different techniques found that plasma EIIIA expression levels increased upon tissue injury.[1,2] The one study reporting increased EIIIB levels was identified with western blot analysis through a previously characterized antibody, which may not recognize the EIIIB segment directly. [7] It should be noted that the antibody failed to recognize full-length EIIIB produced by mammalian cells. Therefore, the small section on EIIIB recognized by the antibody may provide false positives, and a new validation method is required to determine pEIIIB levels precisely. Besides, there was no clear data about the status of EIIIB levels measured serially in the plasma and at a tissue level during skin wound healing. There are several promising studies. However, more experimental studies are needed to reduce the medical costs of chronic wounds. Our current study elucidated a proposed correlation between pEIIIB and tEIIIB by comparing their values at various time points during wound healing. For this purpose, this study compared days 3, 6, 9, 12, and 15 EIIIB levels in the plasma and at a tissue level. This study employed a reproducible and quantitative method to measure both pEIIIB and tissue EIIIB (tEIIIB) levels by RT-qPCR, rather than comparing the levels by two different techniques, an ELISA for pFN determination and a semi-quantitative histological dying method for skin FN measurements, as previously reported. 498

MATERIALS AND METHODS This study was carried out with five to six months old male, white New Zealand rabbits (n=10), with an average of 2.7–3.0 kg after approval from the Animal Research Ethics Committee of our institution. Rabbits were kept in standard test cages at 22–24°C, 12 h light/dark cycle. After their adaptation to the laboratory, they were divided into control (n=2) and study (n=8) groups. All instruments (syringes, clamps, scissors, forceps, and lancets) were immersed in 0.1% diethylpyrocarbonate (DEPC) to prevent DNA and RNA contamination before withdrawing blood and taking tissue samples from the rabbits. Animals were anesthetized using an intramuscular injection of 10–20 mg/kg xylazine (Rompun 2%, Bayer, Istanbul, Turkey) and 50 mg/kg ketamine HCl (Ketalar, Eczacıbaşı Warner-Lambert, Istanbul, Turkey). Intramuscular prophylactic antibiotic (50 mg/kg Ceftriaxone) and analgesic drug (4 mg/kg Carprofen) injections were administered when necessary. In the experimental group, a circular area 2 cm in diameter was drawn on the dorsal region, and its boundaries were determined. A full-thickness skin defect was created by removing skin up to the panniculus carnosus at the base of the floor from the back of the animal. Blood samples, which were used to measure pEIIIB levels, were withdrawn from the marginal ear vein before defects were formed and before each biopsy was taken to measure. Tissue biopsies and blood samples were obtained from the initial wound until healing on days 3, 6, 9, 12, 15. Additionally, in two rabbits, blood samples to measure pEIIIB levels were withdrawn from the marginal ear vein on days 3, 6, 9, 12, 15; these were used for reference values of pEIIIB level for the analyses of pEIIIB levels obtained from the experimental group. Animals were injected with 200 mg/kg intraperitoneal sodium pentobarbital after 15 days. Tissue samples were kept in RNAlater solution and lysed with a MagNA Lyser (Roche, Indianapolis, IN). For lysed tissue samples and blood specimens, centrifugations were performed at 4°C, and plasma samples were frozen at -80°C until analysis. Total RNA was isolated and converted to cDNA (Qiagen, Germantown, MD). Primers (RT2qPCR primer) were obtained from Qiagen (Fibronectin XM_002716425 (Oryctolagus cuniculus fibronectin type III domain containing 3B (FNDC3B), G6PDH XM_002722238). EIIIB levels were measured using RT-qPCR with 25 μl RT2 SYBR Green Mastermix and 40 cycles. The results were analyzed at a Qiagen web portal.

RESULTS In this study, plasma and tissue EIIIB levels from New Zealand rabbits were measured using SYBR Green RT-PCR, using G6PDH as a housekeeping gene. G6PDH was employed as a housekeeping gene. tEIIIB expression increased on day 3 and continued to increase on days 6 and 9, reaching maximum expression on day 12 before starting to decrease. On the Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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Tissue

7 6

[DEĞER] 7.5685

[DEĞER] 8.2439

1 0

[DEĞER] 2.6882

GROUP 1

1 GROUP 2

[DEĞER] 8.5742 [DEĞER] 6.6422

5 4 3 2

1 GROUP 3

1 GROUP 4

0.6 0.4

GROUP 5

[DEĞER] 0.3096 GROUP 1

[DEĞER] 0.2597

[DEĞER] 0.2422

GROUP 2

GROUP 3

[DEĞER] 0.2261 GROUP 4

[DEĞER] 0.2547 GROUP 5

Figure 3. Fold change of pEIIIB expression level. Groups 1, 2, 3, 4, and 5 present days 3, 6, 9, 12, and 15, respectively. ClusterGram

ClusterGram Dimension 2-D

0.8

0.2

Figure 1. Fold change of tissue EIIIB expression level in skin wound tissue. Groups 1, 2, 3, 4, and 5 present days 3, 6, 9, 12, and 15, respectively.

Sample Arroy

Plasma

1.2

Fold change

10 9 8

Join Type Average

Sample Arroy

Color Coded Genes

Dimension 2-D

Join Type Average

Color Coded Genes

min

avg

Group 5 Group 4 Group 3 Group 2 Group 1 ControlGroup

Group 5 Group 4 Group 3 Group 2 Group 1 ControlGroup FN

Magnitude of gene expression max

Magnitude of gene expression min

avg

max

Figure 2. ClusterGram diagram. Control expression color is shown in green and a shift to red from green indicates an increase in expression levels. Groups 1, 2, 3, 4, and 5 present days 3, 6, 9, 12, and 15, respectively.

Figure 4. ClusterGram diagram. Control expression is shown in green and a shift to red from green indicates an increase in expression levels. Groups 1, 2, 3, 4, and 5 present days 3, 6, 9, 12, and 15, respectively.

contrary to the tissue levels, pEIIIB levels gradually decreased until day 15 when expression returned to the initial values. This suggests that early after injury, tEIIIB levels increased, while pEIIIB levels decreased. After fifteen days, tissue levels started to decrease, and pEIIIB expression increased, reaching normal levels. All wounds healed and no chronic wounds were observed. In summary, during wound healing, pEIIIB levels increased, while pEIIIB expression levels decreased simultaneously, and the results were statistically significant. Figures 1–4 show fold change values of the tissue and blood expression levels samples.

qPCR indicated that pEIIIB levels remained close to constant levels, albeit with a slight decrease; however, tEIIIB levels increased dramatically, which is in contrast to the antibodybased EIIIB detection.[6] Furthermore, our results indicated that EIIIB exists in plasma, even under normal physiological conditions. tFN is a mixture of FN isoforms (EIIIB, EIIIA, V, and IIICS), and the isoforms are expressed in association with physiological or pathological conditions, such as wound healing. This correlates with our experimental results, and our study confirms that both and FN express the EIIIB isoform.

We sought to quantify levels of the EIIIB isoform through a more precise method, looking at relative fold change in pEIIIB and tEIIIB levels compared to the expression of the housekeeping gene, G6PDH. pEIIIB expression levels decreased slightly, but the expression levels returned to near initial values after fifteen days. Relative fold change of tEIIIB level was compared to the housekeeping G6PDH gene expression. teIIIB expression levels increased during wound healing and then returned to initial values after two weeks. RT-qPCR can provide accurate results compared to an antibody-based method. Our experimental monitoring of EIIIB expression indicated that pEIIIB levels remain at the same level, with only a slight decrease.

DISCUSSION To our knowledge, this was the first time the experimental monitoring of EIIIB expression measured by SYBR Green RTUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

The wound is damage or an injury of the anatomical, functional integrity for any reason of healthy skin tissue. It can occur for many reasons. Based on the cause, wounds can be classified as an incision, crush, laceration, and perforation, without tissue loss, or wounds with tissue loss.[8,9] Many biological particles, molecules, and different cell types have a part that is involved during all the wound healing phases. Besides, hemostasis, inflammation, cell proliferation, re-epithelialization, and remodeling are in succession take placed in the phases of normal wound healing.[9,10] In the literature, there are many studies revealing new therapeutic approaches or molecular-based recovery period to overcome the difficulty and slow healing processes of chronic wounds, such as diabetic foot, decubitus, and venous leg ulcer. [9,11–15] In clinical practice, to patients with a cutaneous wound, systemic drugs as orally and parenterally can be administered; 499

Kurt Özkaya et al. EIIIB splice variant expression in the wound

however, this may result in the development of several side effects limiting their long-term use. Toxic effects of systemically administered drugs and less predictable drug delivery to the damaged tissue because of possible tissue perfusion problems, there has been an important changing in the clinical tendency toward the local application of chemical agents to improve wound healing. With a large number of local therapeutic approaches, such as platelet-rich plasma, stem cells, growth factors, fibronectin, and many molecules, have achieved promising results in developing wound healing in the experimental studies.[16–18] FN that encoded by a single gene is a 230–270 kDa subunits secreted as a disulfide-bounded a dimeric glycoprotein.; it also is involved in many vital functions of the cell and tissue, such as cellular adhesion, motility, hemostasis, nearly all phases of wound healing, and differentiation.[19,20] FN forms a fibrillary plexus that interacts with many components of ECM and with cell surface receptors.[21] Two forms of FN have been identified: pFN, which is a soluble form, is expressed by hepatocytes into the plasma, and tFN is an insoluble form and expressed locally by fibroblasts and other many cells and deposited into ECM. It is be found in the ECM of embryonic and regenerating or wounds.[19,22] FN includes domain at three regions of the precursor mRNA: IIIA, IIIB IIICS. Although FN is encoded by a single gene, the protein exists in many variant isoforms due to alternative splicing and/or post-translational modifications that help its performance.[5,23] pFN possesses a V domain but does not have EIIIA and EIIIB domains.[22] It has been reported that only very low levels of cellular FN with EIIIA and/or EIIIB domains circulate in blood plasma, and further, levels increase after major trauma.[17,24] No comparison between tissue and pEIIIB expression levels had been investigated before this study. Further, these results were found by employing an antibody to detect the EIIIB domain. The antibody has been shown to fail in recognizing full-length EIIIB produced by mammalian cells. Our experimental set up was based on quantification of the EIIIB isoform through a more precise method. RT-qPCR can provide more accurate results compared to the antibody-based method. FN encouragement the re-epithelialization of the cutaneous wound by stimulating fibroblasts and epidermal cells.[19,25] The wound bad end granulation tissue through which keratinocytes migrate have been found to be rich in pFN, while other basement membrane proteins, laminin, and type IV collagen were found to be absent from beneath the migratory edge of the epidermis.[25,26] FN isoform turnover or splicing is similar to the constitutive and inducible HSP biochemical complementation process. Therefore, at initial wound formation and during wound healing, cells are exposed to stress, and different isoforms of FN may form different functions. pFN is known to be effective in many stages of wound healing, including hemostasis, infection control, the formation of granulation tissue, and epithelialization.[27,28] In conclusion, 500

tissue repair may employ EIIIB for cell migration and proliferation, which is an essential part of healing skin wounds for inward migration of epidermal cells from the edges. Thus, this study shows an essential role of EIIIB in accelerating wound healing. It has been previously reported that topical administration of pFN in chronic wounds positively affects wound healing by affecting fibroblast activity, transforming growth factor-ß1. [9] Recently, it has been reported that the application of the chimeric fibronectin protein to diabetic wounds and corneal epithelial wounds of topical fibronectin-derived peptides accelerates wound healing in the experimental studies.[18,29,30] In this study, both isoforms were detected in the wound, and the healing process was identical to early embryogenesis. Thus, FN splicing during wound healing may be employed during wound healing to create proper forms of FN for tissue repair. A study conducted on spondyloarthropathy patients, comparing rheumatoid arthritis patients and healthy volunteers, indicated that a difference between pFN levels could not be connected to systemic inflammation alone. Rather, the local turnover of EIIIA and EIIIB FN isoforms contributed to the inflamed tissue. Further, the EIIIB FN isoform is thought to be involved in the musculoskeletal inflammatory duration of spondyloarthropathy.[31] This study supports our data on EIIIB levels. Kwon et al.[19,32] conducted the studies investigating pFN administered intravenously or applied topically immediately after wounding enhances incisional wound healing in a rat model. They found that single administration and application of pFN increased wound healing parameters. They suggested that this may be related to the increased amount of hydroxyproline in the healing wound. Their findings supported that sustaining adequate levels of pFN by administering intravenous pFN contributed to the quality of wound healing. As mentioned above, FN is used in experimental studies to examine its role in the wound healing process. Overall, FN has the potential to be a component of new drugs to improve wound healing. There is not enough information about the place of isoforms of FN in different phases of the wound healing process. As a limitation, in this study, other forms of FN were not included in the gene expression trials. In conclusion, the results of our study support the use of EIIIB isoform measured by SYBR Green RT-PCR as the component of the pEIIIB and tEIIIB in a full-thickness cutaneous wound model of the rabbit. Overall, the findings of this study have the potential to lead the development of fibronectin-based biomarkers that can be used to monitor treatment success during the followup of wound healing procedures in clinical practice. Based on this preliminary study, a new fibronectin dependent wound healing scale can be investigated. By conducting many experimental studies in the future, this method, which is more reUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Kurt Özkaya et al. EIIIB splice variant expression in the wound

liable, can be used to look for fibronectin levels and provide guiding measurements on the timing of surgery in difficult-toheal wounds such as diabetic foot and pressure sores. Further studies can shed light on whether EIIIB has merit to become a drug candidate for patients with wound healing problems. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: N.K.Ö., U.Z., K.A.C., Y.T., S.Y.; Design: N.K.Ö., U.Z., K.A.C., Y.T., S.Y.; Supervision: N.K.Ö., Y.T., S.Y.; Fundings: N.K.Ö., U.Z., K.A.C.; Materials: N.K.Ö., U.Z., K.A.C.; Data: N.K.Ö., U.Z., K.A.C., Y.T., S.Y.; Analysis: N.K.Ö., U.Z., K.A.C., Y.T., S.Y.; Literature search: N.K.Ö., U.Z., K.A.C., Y.T., S.Y.; Writing: N.K.Ö., U.Z., K.A.C., Y.T., S.Y.; Critical revision: N.K.Ö., Y.T., S.Y. Conflict of Interest: None declared. Financial Disclosure: This work has been supported by the Scientific Research Project Fund of our University.

REFERENCES 1. Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, Leroux MA. Concise review: role of mesenchymal stem cells in wound repair. Stem Cells Transl Med 2012;1:142−9. 2. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999;341:738−46. 3. Lenselink EA. Role of fibronectin in normal wound healing. Int Wound J 2015;12:313−6. 4. Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci 2002;115:3861−3. 5. To WS, Midwood KS. Plasma and cellular fibronectin: distinct and independent functions during tissue repair. Fibrogenesis Tissue Repair 2011;4:21. 6. Peters JH, Loredo GA, Chen G, Maunder R, Hahn TJ, Willits NH, et al. Plasma levels of fibronectin bearing the alternatively spliced EIIIB segment are increased after major trauma. J Lab Clin Med 2003;141:401−10. 7. Peters JH, Trevithick JE, Johnson P, Hynes RO. Expression of the alternatively spliced EIIIB segment of fibronectin. Cell Adhes Commun 1995;3:67−89. 8. Paul W, Sharma CP. Chitosan and alginate wound dressings: A short review. Trends Biomater Artificial Organs 2004;18:18−23. 9. Al-Rawaf HA, Gabr SA, Alghadir AH. Circulating Hypoxia Responsive microRNAs (HRMs) and Wound Healing Potentials of Green Tea in Diabetic and Nondiabetic Rat Models. Evid Based Complement Alternat Med 2019;2019:9019253. 10. Clark RA. Fibrin and wound healing. Ann N Y Acad Sci 2001;936:355−67. 11. Takeo M, Lee W, Ito M. Wound healing and skin regeneration. Cold Spring Harb Perspect Med 2015;5:a023267. 12. Kallis PJ, Friedman AJ. Collagen Powder in Wound Healing. J Drugs Dermatol 2018;17:403−8. 13. Woodley DT. Distinct Fibroblasts in the Papillary and Reticular Dermis: Implications for Wound Healing. Dermatol Clin 2017;35:95−100.

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14. Kim H, Kong WH, Seong KY, Sung DK, Jeong H, Kim JK, et al. Hyaluronate-Epidermal Growth Factor Conjugate for Skin Wound Healing and Regeneration. Biomacromolecules 2016;17:3694−705. 15. Sahin Inan ZD, Unver Saraydin S. Investigation of the wound healing effects of chitosan on FGFR3 and VEGF immunlocalization in experimentally diabetic rats. Int J Bio Materials Res 2013;1:1−8. 16. Johnson MB, Pang B, Gardner DJ, Niknam-Benia S, Soundarajan V, Bramos A, et al. Topical Fibronectin Improves Wound Healing of Irradiated Skin. Sci Rep 2017;7:3876. 17. Whittam AJ, Maan ZN, Duscher D, Wong VW, Barrera JA, Januszyk M, et al. Challenges and Opportunities in Drug Delivery for Wound Healing. Adv Wound Care (New Rochelle) 2016;5:79−88. 18. Hamed S, Ullmann Y, Egozi D, Daod E, Hellou E, Ashkar M, et al. Fibronectin potentiates topical erythropoietin-induced wound repair in diabetic mice. J Invest Dermatol 2011;131:1365−74. 19. Kwon AH, Qiu Z, Hiraon Y. Effect of plasma fibronectin on the incisional wound healing in rats. Surgery 2007;141:254−61. 20. Tomasini-Johansson BR, Zbyszynski PW, Toraason I, Peters DM, Kwon GS. PEGylated pUR4/FUD peptide inhibitor of fibronectin fibrillogenesis decreases fibrosis in murine Unilateral Ureteral Obstruction model of kidney disease. PLoS One 2018;13:e0205360. 21. Mao Y, Schwarzbauer JE. Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 2005;24:389−99. 22. Magnusson MK, Mosher DF. Fibronectin: structure, assembly, and cardiovascular implications. Arterioscler Thromb Vasc Biol 1998;18:1363−70. 23. Kornblihtt AR, Umezawa K, Vibe-Pedersen K, Baralle FE. Primary structure of human fibronectin: differential splicing may generate at least 10 polypeptides from a single gene. EMBO J 1985;4:1755−9. 24. Jarnagin WR, Rockey DC, Koteliansky VE, Wang SS, Bissell DM. Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis. J Cell Biol 1994;127:2037−48. 25. Takashima A, Billingham RE, Grinnell F. Activation of rabbit keratinocyte fibronectin receptor function in vivo during wound healing. J Invest Dermatol 1986;86:585−90. 26. Ongenae KC, Phillips TJ, Park HY. Level of fibronectin mRNA is markedly increased in human chronic wounds. Dermatol Surg 2000;26:447−51. 27. Sazuka M, Isemura M, Isemura S. Interaction between the carboxyl-terminal heparin-binding domain of fibronectin and (-)-epigallocatechin gallate. Biosci Biotechnol Biochem 1998;62:1031−2. 28. Dooley A, Shi-Wen X, Aden N, Tranah T, Desai N, Denton C, et al. Modulation of collagen type I, fibronectin and dermal fibroblast function and activity, in systemic sclerosis by the antioxidant epigallocatechin-3-gallate. Rheumatology (Oxford) 2010;49:2024−36. 29. Hocking DC, Brennan JR, Raeman CH. A Small Chimeric Fibronectin Fragment Accelerates Dermal Wound Repair in Diabetic Mice. Adv Wound Care (New Rochelle) 2016;5:495−506. 30. Morishige N, Uemura A, Morita Y, Nishida T. Promotion of Corneal Epithelial Wound Healing in Diabetic Rats by the Fibronectin-Derived Peptide PHSRN. Cornea 2017;36:1544−8. 31. Claudepierre P, Allanore Y, Belec L, Larget-Piet B, Zardi L, Chevalier X. Increased Ed-B fibronectin plasma levels in spondyloarthropathies: comparison with rheumatoid arthritis patients and a healthy population. Rheumatology (Oxford) 1999;38:1099−103. 32. Kwon AH, Qiu Z, Hirao Y. Topical application of plasma fibronectin in full-thickness skin wound healing in rats. Exp Biol Med (Maywood) 2007;232:935−41.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Tavşan yara modelinde RT-PCR yöntemi ile seri olarak ölçülen plazma ve doku fibronektin EIIIB splice değerlerinin ölçümleri Dr. Neşe Kurt Özkaya,1 Dr. Umut Zereyak,2 Dr. Kübra Açıkalın Coşkun,3 Dr. Yusuf Tutar,4 Dr. Sarper Yılmaz5 Sivas Cumhuriyet Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif Estetik Cerrahi Anabilim Dalı, Sivas Özel Medicana Hastanesi, Plastik Rekonstrüktif Estetik Cerrahi Birimi, Sivas Sivas Cumhuriyet Üniversitesi Tıp Fakültesi, Araştırma Merkezi, Sivas 4 Sağlık Bilimleri Üniversitesi, Eczacılık Fakültesi ve Moleküler Tıp Programı, İstanbul 5 Ufuk Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif Estetik Cerrahi Anabilim Dalı, Ankara 1 2 3

AMAÇ: Fibronektin (FN), hücre dışı matriksin vazgeçilmez bir parçasıdır. Rejenerasyon veya yara iyileşmesi sırasında FN’nin plazma formu, geçici bir fibrin-FN matrisi oluşturmak için fibrin pıhtılarına dahil olur ve ayrıca lokal olarak sentezlenen hücresel FN, yaralı dokuyu rejenere etmek için pıhtıya göç eder. Bu çalışmada tavşanlarda deneysel yara iyileşme modelinde yara dokusu EIIIB ve plazma EIIIB ekspresyon düzeylerini incelemeyi amaçladık. GEREÇ VE YÖNTEM: Plazma ve doku EIIIB ekspresyon düzeyleri, tavşanların kutanöz yara modelinde RT-qPCR ile seri olarak ölçüldü. BULGULAR: Doku FN ekspresyonu 3. günden başlayarak arttı, 6. ve 9. günlerde artmaya devam etti, azalmaya başlamadan önce 12. günde maksimum ekspresyona ulaştı. Doku seviyelerinin aksine, plazma FN seviyeleri ekspresyon başlangıç değerlerine döndüğünde 15. güne kadar kademeli olarak azaldı. TARTIŞMA: Sonuç olarak, mevcut çalışmanın bulguları, yara iyileşmesi sırasında doku EIIIB ekspresyon seviyesinin arttığını desteklemektedir; plazma EIIIB ekspresyon seviyesi minimum düzeyde azalır. Bu, plazma FN’nin geçici olarak ECM oluşumuna yardımcı olduğu raporların aksine değerlerdir. Bu nedenle verilerimiz, yara iyileşme sürecini hızlandırmada EIIIB’nin doku düzeyinde önemli bir rol oynadığını göstermektedir. Ayrıca, deneyde kullandığımız ölçme yöntemimiz olan RT-qPCR yöntemi, antikor bazlı yöntemlere kıyasla daha doğru ve kesin sonuçlar sağlayabilir. Anahtar sözcükler: Fibronektin; plazma fibronektin EIIIB; RT-qPCR; tavşan; yara iyileşmesi. Ulus Travma Acil Cerrahi Derg 2020;26(4):497-502

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doi: 10.14744/tjtes.2020.25260

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EXPERIMENTAL STUDY

Effects of garlic oil (allium sativum) on acetic acid-induced colitis in rats: Garlic oil and experimental colitis Yusuf Tanrıkulu, M.D.,1 Ceren Şen Tanrıkulu, M.D.,2 Murat Can, M.D.,4 Fürüzan Köktürk, M.D.5

Fahriye Kılınç, M.D.,3

Department of General Surgery, KTO Karatay University Faculty of Medicine, Konya-Turkey

Department of Emergency Medicine, University of Health Sciences, Konya Training and Research Hospital, Konya-Turkey

Department of Pathology, Necmettin Erbakan University Meram Faculty of Medicine, Konya-Turkey

Department of Biochemistry, Bülent Ecevit University Faculty of Medicine, Zonguldak-Turkey

Department of Biostatistics, Bülent Ecevit University Faculty of Medicine, Zonguldak-Turkey

ABSTRACT BACKGROUND: Inflammatory bowel disease (IBD) is an important health problem. The most important hypotheses for the pathogenesis of this disease are the deterioration of immune responses and loss of tolerance against bacteria in the enteric flora. Although IBD has been widely investigated, its treatment remains difficult. This study aims to investigate the effects of garlic oil (GO) on an experimental colitis model. METHODS: Twenty-eight rats were randomly divided into four equal groups as follows: group 1 (sham), group 2 (control), group 3 (topical treatment) and group 4 (topical and systemic treatment). An acetic acid-induced colitis model was produced in groups 2, 3 and 4 and was administered normal saline, topical GO and topical and systemic GO, respectively. RESULTS: Hydroxyproline levels were lower in the treatment groups than in the control group. TNF-α levels were significantly lower in group 3 than in group 2. Macroscopic scores were significantly lower in group 4 than in group 2. Significant differences were observed between the treatment and control groups according to their epithelial loss. CONCLUSION: GO can reduce colonic damage and inflammation in the acetic acid-induced colitis model, with effects on both local and systemic treatments, but with a more pronounced effect in local treatment. Keywords: Acetic acid; colitis; diallyl sulphide; garlic oil; inflammatory bowel disease; TNF-α.

INTRODUCTION Inflammatory bowel disease (IBD), mainly includes ulcerative colitis (UC) and Crohn’s disease (CD), is an inflammatory disease primarily involving the gastrointestinal tract. While various infectious agents, allergens, nutrition habits, psychosomatic factors and immune responses to auto-antigens take part in the etiology of IBD, changes in the balance of mucosal protective factors and excessive bacterial proliferation, as well as changes in cytokine and mediator synthesis, can be responsible for the pathogenesis of this disease.[1–3] The most important hypotheses for the pathogenesis of IBD are both

deterioration of immune reactions and lack of tolerance to bacteria in the enteric flora. The fundamental changes seen in the immune reaction are an increase in macrophage counts and activation of dendritic cells in the lamina propria, which causes nuclear factor κB (NFκB) stimulation, and proinflammatory cytokines (interleukin (IL)1β, tumour necrosis factor (TNF)-α, IL-6 and IL-8) production, as well as increased expression of adhesion molecules. [4,5] Therefore, the development of colitis can be reduced with many experimental agents, which cause changes in the immune response as well as the release of inflammatory molecules.

Cite this article as: Tanrikulu Y, Şen Tanrıkulu C, Kılınç F, Can M, Köktürk F. Effects of garlic oil (allium sativum) on acetic acid-induced colitis in rats: Garlic oil and experimental colitis. Ulus Travma Acil Cerrahi Derg 2020;26:503-508. Address for correspondence: Yusuf Tanrıkulu, M.D. KTO Karatay Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Konya, Turkey Tel: +90 332 - 221 80 80 E-mail: drtanrikulu@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):503-508 DOI: 10.14744/tjtes.2019.01284 Submitted: 13.06.2019 Accepted: 05.11.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Hydroxyproline is an important constituent of the major structural protein and plays a key role in the synthesis and stability of the collagen. A normal and stable cellular structure of the extracellular matrix is a sign of a complete wound healing process after a tissue injury. Increased hydroxyproline content in granulation tissue is the indicator of increased collagen turnover, which indicates better maturation and proliferation of collagen during wound healing. Therefore, IBD shows both acute and chronic wound healing, measurement of tissue hydroxyproline levels contributes to revealing wound healing.[6] Garlic oil (GO) is beneficial to human health and contains effective natural organosulfur compounds, such as allicin, allium, diallyl sulphide (DAS) and diallyl trisulphide (DATS).[7] Because GO has a broad diversity of pharmacological properties including anticancer, antibacterial, anti-inflammatory, fibrinolytic, wound-healing, antioxidant and anti-adhesive, it has been used in many different areas of clinical medicine. [8,9] Studies have shown that purified garlic compounds inhibit NFκB activation and TNF-α production.[10] Another study found that DAS inhibits both pro- and anti-inflammatory cytokines, including TNF-α, IL-1β, IL-6 and IL-10, in LPS (lipopolysaccharide)-stimulated RAW264.7 macrophages. [11] In this study, we presented the effects of GO on cellular damage and inflammation in an acetic acid-induced colitis rat model.

MATERIALS AND METHODS Study Design Twenty-eight female adult Wistar–Albino rats, weighing 260 ± 20 g, were enclosed at room temperature (22 °C ± 1 °C) with 12 h:12 h light/dark cycle and fed a standard diet and water. Diet and water were stopped 12 h and 2 h, respectively, before inducing anaesthesia. No antibiotics were administered during the experiment. The experimental protocol was accepted by the Animal Ethics Committee of Bülent Ecevit University (Date/Number: 2014/13b).

Induction of the colitis model The rats were anaesthetised with intramuscular ketamine (50 mg/kg) and xylazine (6 mg/kg). After inducing anaesthesia, 1 mL of (5%) acetic acid (AA) was instilled using a soft 6-Fr paediatric catheter inserted into the anus up to 6–8 cm. Eventually, after 15–20 seconds of exposure, the fluid was withdrawn. Before the withdrawal of the catheter, 2 mL of air was applied to distribute AA into the colon. In the treatment groups, the GO was administered one hour after induction. This experimental model has been shown to have similar histopathological features in human colitis.[12]

Group 1 (Sham): After each rat was rectally administered saline, 1 mL of saline was intraperitoneally applied. Group 2 (Control): After the colitis model was produced, 1 mL of saline was intrarectally applied. No treatment was administered. Group 3 (Topical treatment): One hour after the colitis model was produced, 5 mL/kg of GO (Oleum Allii Sativi®, Arifoglu, Avcilar, İstanbul) was rectally applied. The rats were incubated for 10 min in a Trendelenburg position to provide sufficient mucosal contact with the drug. Subsequently, 1 mL of saline was intraperitoneally administered. Group 4 (Topical + systemic treatment): One hour after the colitis model was produced, 5 mL/kg of GO was rectally administered. The rats were kept in Trendelenburg position for 10 minutes to ensure adequate drug-mucosal interaction. Subsequently, 5 mL/kg of GO was intraperitoneally applied as a single daily dose for 10 days. On the tenth day, the abdomen and thorax were opened by a midline incision under anesthesia. Blood samples were taken by cardiac puncture method for biochemical analysis and rats were sacrificed by the same method. Later, the distal 8 cm of the colon was extracted for histopathological evaluation.

Histopathological Examination After cleaning the mucosa with saline, the mucosal injury was macroscopically evaluated using the grading scale of Morris et al.[13] (Table 1). A single well-experienced pathologist, who was also blind for the study design, examined each specimen. For this examination, 8 cm distal colon samples were obtained. The colon samples were fixed using 10% formaldehyde, and4-µm-thick tissue samples in paraffin blocks were obtained and stained with haematoxylin and eosin (H&E) and then analysed under a light microscope (Olympus BX53, Tokyo, Japan). The degree of inflammation of the colon was semiquantitatively graded from 0 to 11, according to the criteria defined by Özgün et al.[14] (Table 2). Table 1. Variables used for macroscopic evaluation[13] Score

Macroscopic variable

No damage

Localized hyperemia, but no ulcers

Linear ulcers with no significant inflammation

Linear ulcer with inflammation at one site

Two or more sites of ulceration and/or inflammation

Two or more major sites of inflammation and

Experimental Groups

ulceration or one more site of inflammation and

Twenty-eight rats were randomly divided into four equal groups. The colitis model was produced in all groups except the sham group.

ulceration extending >1 cm along the length of

the colon

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Table 2. Variables used in the classification of the inflammatory histological score[14] Score

Epithelial loss

Inflammatory infiltrate

Integrity of crypts

Stress to goblet cells

0 None

None

Intact

Absent

1 <5%

Mild

<10%

Present

2 5–10%

Moderate

10–20%

N/A

3 >10%

Severe

>20%

N/A

Mean±SD Mean±SD

(OD) was measured under 450 nm wavelengths with a microplate reader. According to standards concentration, the corresponding OD values were calculated using the standard curve linear regression equation to calculate the corresponding sample’s concentration.

Grup 1 (Sham)

3.55±0.48

26.93±6.35

Statistical Analysis

Grup 2 (Control)

4.98±0.59

60.82±26.05

Grup 3 (Topical treatment)

2.95±0.70x 45.99±8.97a

Grup 4 (Topical+ systemic

3.17±1.11y 50.16±24.33

Table 3. Comparison of groups according to biochemical results Groups

Hydroxyproline TNF-α

treatment) TNF-α: Tumor necrosis factor alpha; SD: Standard deviation. x p=0.002, yp=0.015, and ap=0.008 vs. control groups.

Biochemical Analysis Blood Blood was collected into tubes at the time of death. Blood samples were centrifuged at 1000 g for 10 minutes at 4°C to remove plasma. Aliquots of the samples were transferred into polyethylene tubes to be used in the assay of biochemical parameters and were stored at -80°C until analysis. TNF-α levels were measured in the serum using a rat TNF alpha ELISA kit (Eastbiopharm, Hangzhou) on fully automatic devices. Tissue All tissues were washed twice with cold saline solution, placed into glass bottles, labeled, and stored in a deep freezer (-80°C) until processing. Colon tissues were homogenized in 10 volumes of 150 mM ice-cold KCL using a glass Teflon Homogenizer (Ultra Turrax IKA T18 Basic; IKA, Wilmington, NC, USA) after cutting the tissues into small pieces with scissors (for two minutes at 5000 rpm). The homogenate was then centrifuged 5000 g for 15 minutes. The supernatant was used for analysis. Later, spectrophotometry was used to detect tissue hydroxyproline concentrations, and the results were denoted as micrograms per milligram of tissue.[15] First, the samples, standards, and streptavidin-HRP were added to the well. The antibodies were labeled with an enzyme, and the plate was incubated for 60 minutes at 37ºC. The plate was washed five times, and chromogen solutions were added. The plate was incubated for 10 minutes at 37ºC, and the stop solution was added into the wells. The optical density Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Results were analysed using the SPSS (Statistical Package for Social Science) for Windows 19.0 package programme. The normality of the data was determined using the one-sample Kolmogorov–Smirnov test. Continuous variables were analysed using the Kruskal–Wallis variance analysis. While continuous variables were expressed as mean ± standard error, non-continuous variables were expressed as the median (min–max). The chi-square test was used to compare noncontinuous variables. A P-value of <0.05 was considered to be a statistically significant difference for all tests.

RESULTS Hydroxyproline and TNF-α results of all groups are summarised in Table 3. Hydroxyproline levels in the treatment groups were significantly lower than the control group (p=0.002, group 3; p=0.015, group 4). There was no difference in the TNF-α levels between groups 2 and 4; however, they were significantly lower in group 3 than TNF-α levels in the control group (p=0.008). The distribution of the histopathological results is summarised in Table 4 and is shown in Fig. 1. The method described by Morris et al.[13] was used to assess macroscopic damage in the colon samples. The results of the macroscopic scores in group 4 were significantly lower than those in the control group (p=0.015). Microscopic damage was also evaluated according to criteria defined by Özgün et al.[14] The sham group had histopathological findings similar to the normal colonic mucosa. There was a significant difference between the treatment groups and the control group as it relates to epithelial loss (p=0.001, group 3; p=0.021, group 4). There was no difference between the groups in terms of inflammatory infiltrate, the integrity of crypts and stress to goblet cells. The total damage score was significantly lower in the treatment groups compared to the control group (p=0.001). 505

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(a)

(b)

(c)

(d)

Figure 1. In the sham group: the mucosal surface epithelium and crypts in the colon wall are regular structures and a large number of goblet cells are observed. The stromal structure between the crypts is thin and few mononuclear cells are observed (a). In the control group: in the surface and crypt epithelium, there is a decrease in goblet cells, irregularity in crypts, and expansion between crypts and stroma in the submucosa. Inflammatory mixed cells infiltrating the epithelium and crypt abscess (arrow) in one focus are seen (b). In the local treatment group: there is a mild irregularity in the crypts, with a decrease and a slight increase in the stroma between them, a decrease in the goblet cells in the surface epithelium and fewer crypts, inflammatory cell infiltration in the lamina propria and submucosa (c). In the systemic treatment group: there is a slight decrease in goblet cells, a slight decrease in crypts, irregularity in crypts and mild enlargement of the stroma between them. Mixed inflammatory cells in the lamina propria and submucosa are observed (d) (Hematoxylin-eosin, x100).

DISCUSSION The present study indicates that systemic and local administration of GO reduces the inflammation and cellular damage in an AA-induced colitis model. IBDs, including UC and CD, are inflammatory diseases that primarily affect the gastrointestinal tract. The etiopathogenesis of the disease is multifactorial. While various infectious agents, allergens, nutrition habits, psychosomatic factors and immune response to auto-antigens take part in the etiology of IBDs, changes in the balance of mucosal protective factors and excessive bacterial proliferation as well as changes in cytokine and mediator synthesis can be responsible for the pathogenesis of the disease.[1–3] The most important hypotheses for the pathogenesis of the disease are both deterioration of immune reactions and lack of tolerance against bacteria in the enteric flora. This inappropriate inflammatory response disrupts micro-vascular structures, increases vascular permeability and destroys the intestinal epithelial barrier. Because endothelial cells are the main cells of microvascular structures, cellular damage becomes inevitable.[16,17] Many proinflammatory cytokines are upregulated in IBD, of which TNF-α and IL-1 are the most important. TNF-α is the 506

main mediator of intestinal inflammation. It is synthesised by many inflammatory cells and activates many genes in the NFκB pathway. Other important mechanisms accused in the pathogenesis of IBD include oxidative stress and reactive oxygen products. Reactive oxygen products that are formed due to oxidative stress cause mucosal damage along with proinflammatory mediators. Therefore, the effects of various antioxidant and anti-inflammatory agents have been the subject of research in IBD.[18,19] Garlic has been used in many fields of medicine for centuries. The part of the garlic that is responsible for its biological activity is the active organosulphuric compounds, which include allicin, alliin, DAS and DATS. Many studies have shown that garlic compounds have antioxidant, antimicrobial, antimutagenic and anticancer properties.[20,21] Ho et al.[21] found that DAS reduces TNF-α in rat aortic smooth muscles and suggested that DAS could prevent oxidative stress in inflammation. Furthermore, immunohistochemical studies have indicated that DAS reduces inflammatory biomarkers, such as TNF-α and IL-1β, by affecting inducible nitric oxide synthase (iNOS) and activating NFκB.[21,23] Another study demonstrated that allicin inhibits NFκB activation as well as TNF-α and iNOS production.[10] Likewise, it was shown that DAS Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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inhibits both pro- and anti-inflammatory cytokines in LPS-stimulated macrophages.[11] Very few studies that investigate the effects of garlic on intestinal diseases are available in the literature. Balaha et al.[24] showed that GO reduces inflammation in the UC model. Blackler et al.,[25] in their studies investigating the protective effects of hydrogen sulphide on encephalopathy associated with naproxen, found that the co-administration of DAS reduced naproxen-induced intestinal injury and inflammation. In another study, Voltes et al.[26] found that topically applied hydrocortisone, pectin/alginate and olive oil combination may be effective against inflammatory infiltration in the colitis model. In our study, we found that TNF-α levels in the topical treatment group were lower than those in the control group (p=0.008). Although TNF-α levels were also lower in systemic + topical treatment, the results were not significant. Hydroxyproline is an important constituent of the major structural protein and plays a key role in the synthesis and stability of the collagen. Hydroxyproline is an important indicator of collagen accumulation. Deficiency of protein during wound healing may diminish new capillary development, fibroblast proliferation, collagen and proteoglycans synthesis and remodeling and contraction of the wound. A normal and stable cellular structure of the extracellular matrix is a sign of a complete wound healing process after a tissue injury. Breakdown of collagen releases free hydroxyproline and its peptides. Thus, hydroxyproline as a biochemical marker during wound healing is extensively used to evaluate the tissue collagen content and as an indicator for collagen turnover after wound-healing. Increased hydroxyproline content in granulation tissue is the indicator of increased collagen turnover, which indicates better maturation and proliferation of collagen during wound healing. There are numerous reasons to support the use of hydroxyproline as a biomarker of the collagen content within tissues after the wound-healing process as it is abundantly found in collagen and plays a vital role in wound healing.[6] Sadar et al.[27] found that increased hydroxyproline levels significantly correlated with accumulated collagen in the colonic tissue after trinitrobenzene sulfonic acid (TNBS) administration, whereas ferulic acid treatment significantly reduced colonic hydroxyproline activity. Motawi et al.[28] also found similar results. In our study, we found that hydroxyproline levels were significantly higher in the control group and significantly lower in the treatment groups, which was in accordance with the literature (p=0.002, topical treatment group; p=0.015, topical + systemic treatment group). Macroscopic and histopathological examinations are the gold standard for evaluating inflammatory in the colon. Appleyard and Wallace[29] found that total histopathological damage score was higher in the colitis group compared to the saline group in the original colitis studies in which they underwent histopathological evaluation. Balaha et al.[24] found that GO ameliorated the marked macroscopic and microscopic Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

changes of colonic mucosa in a dose-dependent manner. In our study, we found that the total damage score was significantly lower in the treatment groups compared to the control group (p=0.001).

Conclusion In conclusion, GO able to inhibit AA-induced colitis in rats, maybe through its anti-inflammatory and immunomodulatory properties. This effect is seen in both local and systemic treatments; however, the effect is more pronounced in local treatment. Moreover, further investigations are currently in progress to determine the precise underlying protective mechanism of GO on AA-induced colitis. Therefore, GO can be used both to reduce cellular damage and disease severity during the exacerbation period and to be recommended as a protective agent recommended for UC patients.

Acknowledgements We would like to thank the employees of the operating room and the Department of Pathology. Ethics Committee Approval: The Ethics Committee approval for this study was received from the Ethics Committee of Bülent Ecevit University Faculty of Medicine. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Y.T..; Design: Y.T., C.Ş.T.; Supervision: Y.T., C.Ş.T.; Fundings: Y.T.; Materials: Y.T., C.Ş.T., Fah.K., M.C., Für.K; Data: Y.T., C.Ş.T.; Analysis: Y.T.; Literature search: Y.T.; Writing: Y.T.; Critical revision: Y.T. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Safarpour AR, Hosseini SV, Mehrabani D. Epidemiology of inflammatory bowel diseases in iran and Asia; a mini review. Iran J Med Sci 2013;38:140–9. 2. Daneshmand A, Mohammadi H, Rahimian R, Habibollahi P, Fakhfouri G, Talab SS, et al. Chronic lithium administration ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats; potential role for adenosine triphosphate sensitive potassium channels. J Gastroenterol Hepatol 2011;26:1174−81. 3. Nagib MM, Tadros MG, ElSayed MI, Khalifa AE. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats. Toxicol Appl Pharmacol 2013;271:106–13. 4. Sartor RB, Hoentjen F. Proinflammatory cytokines and signaling pathways in intestinal innate immune cells. In: Mucosal Immunology. Mestecky J, Lamm ME, Ogra P, Strober W, Bienenstock J, McGhee JR, et al, editors. 3rd edition. Elsevier Inc 2005.p.681−701. 5. Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 1996;157:1261−70. 6. Yun HM, Ban JO, Park KR, Lee CK, Jeong HS, Han SB, et al. Potential therapeutic effects of functionally active compounds isolated from garlic.

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Tanrıkulu et al. Effects of garlic oil (allium sativum) on acetic acid-induced colitis in rats Pharmacol Ther 2014;142:183−95. 7. Srivastava AK, Khare P, Nagar HK, Raghuwanshi N, Srivastava R. Hydroxyproline: A Potential Biochemical Marker and Its Role in the Pathogenesis of Different Diseases. Curr Protein Pept Sci 2016;17:596–602. 8. Sakthivel KM, Guruvayoorappan C. Amentoflavone inhibits iNOS, COX-2 expression and modulates cytokine profile, NF-κB signal transduction pathways in rats with ulcerative colitis. Int Immunopharmacol 2013;17:907–16. 9. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982;78:206–9. 10. Bruck R, Aeed H, Brazovsky E, Noor T, Hershkoviz R. Allicin, the active component of garlic, prevents immune-mediated, concanavalin A-induced hepatic injury in mice. Liver Int 2005;25:613–21. 11. Chang HP, Huang SY, Chen YH. Modulation of cytokine secretion by garlic oil derivatives is associated with suppressed nitric oxide production in stimulated macrophages. J Agric Food Chem 2005;53:2530–4. 12. Randhawa PK, Singh K, Singh N, Jaggi AS. A review on chemical-induced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol 2014;18:279–88. 13. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989;96:795–803. 14. Özgün E, Sayılan Özgün G, Eskiocak S, Yalçın Ö, Süer Gökmen S. Effect of L-carnitine on serum paraoxonase, arylesterase and lactonase activities and oxidative status in experimental colitis. Turk J Biochem 2013;38:145−53. 15. Bergman R, Loxley R. Two improved and simplified methods for the spectrophotometric determination of OH-proline. Anal Chem 1963;35:1961–5. 16. Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002;347:417– 29. 17. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007;448:427–34. 18. Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol 1993;45:367–74.

19. Kalaycı MU, Eroğlu HE, Kubilay D, Soylu A, Sancak B, Uğurluoğlu C, et al. The effects of methylene blue on adhesion formation in a rat model of experimental peritonitis. Ulus Travma Acil Cerrahi Derg 2011;17:205−9. 20. Hall A, Troupin A, Londono-Renteria B, Colpitts TM. Garlic Organosulfur Compounds Reduce Inflammation and Oxidative Stress during Dengue Virus Infection. Viruses 2017;9:159. 21. Ho CY, Weng CJ, Jhang JJ, Cheng YT, Huang SM, Yen GC. Diallyl sulfide as a potential dietary agent to reduce TNF-α- and histamineinduced proinflammatory responses in A7r5 cells. Mol Nutr Food Res 2014;58:1069–78. 22. Suman S, Shukla Y. Diallyl Sulfide and Its Role in Chronic Diseases Prevention. Adv Exp Med Biol 2016;929:127–44. 23. Kalayarasan S, Sriram N, Sudhandiran G. Diallyl sulfide attenuates bleomycin-induced pulmonary fibrosis: critical role of iNOS, NF-kappaB, TNF-alpha and IL-1beta. Life Sci 2008;82:1142–53. 24. Balaha M, Kandeel S, Elwan W. Garlic oil inhibits dextran sodium sulfate-induced ulcerative colitis in rats. Life Sci 2016;146:40–51. 25. Blackler RW, Motta JP, Manko A, Workentine M, Bercik P, Surette MG, et al. Hydrogen sulphide protects against NSAID-enteropathy through modulation of bile and the microbiota. Br J Pharmacol 2015;172:992−1004. 26. Voltes A, Bermúdez A, Rodríguez-Gutiérrez G, Reyes ML, Olano C, Fernández-Bolaños J, et al. Anti-Inflammatory Local Effect of Hydroxytyrosol Combined with Pectin-Alginate and Olive Oil on Trinitrobenzene Sulfonic Acid-Induced Colitis in Wistar Rats. J Invest Surg 2020;33:8−14. 27. Sadar SS, Vyawahare NS, Bodhankar SL. Ferulic acid ameliorates TNBS-induced ulcerative colitis through modulation of cytokines, oxidative stress, iNOs, COX-2, and apoptosis in laboratory rats. EXCLI J 2016;15:482–99. 28. Motawi TK, Rizk SM, Shehata AH. Effects of curcumin and Ginkgo biloba on matrix metalloproteinases gene expression and other biomarkers of inflammatory bowel disease. J Physiol Biochem 2012;68:529–39. 29. Appleyard CB, Wallace JL. Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs. Am J Physiol 1995;269:G119–25.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçanlarda asetik asitle indüklenen kolit üzerine sarımsak yağının etkileri: Sarımsak yağı ve deneysel kolit Dr. Yusuf Tanrıkulu,1 Dr. Ceren Şen Tanrıkulu,2 Dr. Fahriye Kılınç,3 Dr. Murat Can,4 Dr. Fürüzan Köktürk5 KTO Karatay Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Konya Sağlık Bilimleri Üniversitesi, Konya Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Konya Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Patoloji Anabilim Dalı, Konya 4 Bülent Ecevit Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Zonguldak 5 Bülent Ecevit Üniversitesi Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Zonguldak 1 2 3

AMAÇ: Enflamatuvar bağırsak hastalığı (EBD) önemli bir sağlık sorunudur. Hastalığın patogenezinde ileri sürülen en önemli hipotezler bağırsak florasındaki bakterilere karşı tolerans kaybı ve immün yanıtın bozulmasıdır. Çok geniş araştırmalara rağmen, EBD’nin tedavisi hala zordur. Bu çalışmada deneysel kolit modelinde sarımsak yağının (GO) etkilerinin araştırılması amaçlandı. GEREÇ VE YÖNTEM: Yirmi sekiz sıçan rastgele dört eşit gruba ayrıldı; grup 1 (sham), grup 2 (kontrol), grup 3 (topikal tedavi grubu) ve grup 4 (topikal ve sistemik tedavi grubu). Grup 2, 3 ve 4’te asetik asitle indüklenen kolit modeli oluşturuldu. Grup 2’ye salin, grup 3’e topikal GO ve grup 4’e topikal ve sistemik GO verildi. BULGULAR: Hidroksiprolin seviyeleri tedavi gruplarında kontrol grubundan daha düşüktü. Grup 3’teki TNF-α seviyeleri kontrol grubuna göre anlamlı olarak düşüktü. Makroskopik skorları grup 4’te kontrol grubundan anlamlı olarak düşüktü. Tedavi grupları ve kontrol grubu arasında epiteliyal kayba göre anlamlı fark gözlendi. TARTIŞMA: Sarımsak yağı asetik aside bağlı kolit modelinde kolonik hasarı ve enflamasyonu azaltır. Bu etki, topikal uygulamada daha belirgin olmakla birlikte hem topikal hem de sistemik uygulamada ortaya çıkmaktadır. Anahtar sözcükler: Asetik asit; dialil sülfit; enflamatuvar bağırsak hastalığı; kolit; sarımsak yağı; TNF-α. Ulus Travma Acil Cerrahi Derg 2020;26(4):503-508

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doi: 10.14744/tjtes.2019.01284

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EXPERIMENTAL STUDY

Effects of sugammadex on ischemia reperfusion in a rat extremity model Ali Alagöz, M.D.,1 Semih Küçükgüçlü, M.D.,2 Nilay Boztaş, M.D.,2 Volkan Hancı, M.D.,2 Esin Yuluğ, M.D.,3 Ali Rıza Şişman, M.D.4 1

Department of Anesthesiology, Foca State Hospital, İzmir-Turkey

Department of Anesthesiology and Reanimation, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

Department of Histology and Embryology, Karadeniz Technical University Faculty of Medicine, Trabzon-Turkey

Department of Biochemistry, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: The hypothesis of our study is that sugammadex has protective efficacy against ischemia-reperfusion (I/R) injury in rats. METHODS: Our study included 28 male Wistar Albino rats. The rats were assigned to four groups. The sham group had no procedure other than anesthesia administration. The control group received three hours of ischemia and 24 hours of reperfusion. The Sgdx4 group received 4 mg/kg, and the Sgdx16 group received 16 mg/kg sugammadex intravenously, and then, reperfusion was applied. Histopathological investigation, and serum creatine kinase (CK), lactate dehydrogenase (LDH), and serum and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) analyses were performed. RESULTS: When the sham group and the control group were compared, there were statistically significant differences histopathologically (p<0.01). There was no significant difference between the Sgdx4 group compared with the sham and control groups histopathologically (p>0.01). There was a significant difference between the Sgdx16 group and the sham group histopathologically (p<0.01). There were significant differences between the sham and control groups concerning CK and LDH levels (p<0.01). There was a significant difference in the levels of CK between the control group and Sgdx4 group and in the levels of CK and LDH between the control group and Sgdx16 group (p<0.01). CONCLUSION: In our study, we examined the histological and biochemical protective effects of 4 mg/kg sugammadex on unilateral lower extremity I/R injury in rats. The findings suggest that a 4 mg/kg dose of sugammadex was more effective than a 16 mg/kg dose. Keywords: Ischemia; lower extremity; reperfusion; sugammadex.

INTRODUCTION Ischemia-reperfusion (I/R) is defined as renewed blood flow to a tissue or organ after a reduction or cessation of blood flow.[1] Reperfusion may cause more injury to tissues compared to the original injury that arises from ischemia, which is called I/R injury.[2] Injury due to I/R is the basis of the physiopathology linked to surgical interventions and thrombolytic treatments like cerebral ischemia, stroke, hemorrhagic shock, aorta/peripheral artery cross-clamping, thromboembolism,

myocardial infarction, tourniquet application, and organ transplantation.[3] Skeletal muscle ischemia is generally observed in the lower extremities, together with trauma, hemorrhage, vein blockage, and thromboembolic formations.[4] I/R in the lower extremities is a common and clinically important event. In the reperfusion period after extremity ischemia, there is a clear increase in morbidity and mortality as a result of systemic complications. While edema and muscle necrosis may occur locally, problems, such as systemic inflammatory response and multiple organ failure, may be encountered with

Cite this article as: Alagöz A, Küçükgüçlü S, Boztaş N, Hancı V, Yuluğ E, Şişman AR. Effects of sugammadex on ischemia reperfusion in a rat extremity model. Ulus Travma Acil Cerrahi Derg 2020;26:509-516. Address for correspondence: Nilay Boztaş, M.D. Dokuz Eylül Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İzmir, Turkey Tel: +90 232 - 412 28 01 E-mail: nilayboztas@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):509-516 DOI: 10.14744/tjtes.2019.12524 Submitted: 19.11.2018 Accepted: 10.11.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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advancing reperfusion.[5] The method used in many operations involving a tourniquet is a model for I/R. The advantages of using a tourniquet include ensuring a bloodless environment and making the operation easier, reducing hemorrhage, limiting transfusion requirements, and surgery duration.[6] Neuroprotective effects of various cyclodextrins have been shown in previous studies. Methyl-β-cyclodextrin has been found to protect the hippocampal areas from the effects of anoxia.[7] Frank et al.[8] reported that as with other β-cyclodextrins, methyl-β-cyclodextrin reduced neuronal excitability in the hippocampal area because methyl-β-cyclodextrin treatment may separate cholesterol in the postsynaptic area, causing disruption of the NMDA receptor and α-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptorlinked glutamate transmission. Many agents have been studied previously to assess their efficacy on I/R. Among these are beta cyclodextrins. Previous studies have shown a variety of beta cyclodextrins to have positive effects on I/R injury.[7,9] Another agent in the cyclodextrin family is the gamma-cyclodextrin of sugammadex, and this compound has begun to be commonly used in anesthesia practice.[10,11] However, in our literature analysis, no study researching the efficacy of sugammadex on muscle I/R injury was found. Our hypothesis is that Sugammadex has a protective effect on Ischemia Reperfusion injury in the rat extremity model. This study aims to induce an I/R model by applying a tourniquet to the lower extremity of rats and to assess the effects of intravenous (IV) 4 mg/kg and 16 mg/kg doses of sugammadex on skeletal muscle I/R injury.

MATERIALS AND METHODS Our study was completed in the Animal Experiments Laboratory after receiving permission from the Animal Experiments Local Ethics Committee (Ethic No: 15/2016. Date 23/03/2016). This study included 28 male Wistar rats weighing from 250–300 g. They were monitored under standard laboratory conditions (12-hour day/night cycle, 20–22°C, 50%–60% humidity).

was performed apart from anesthesia administration. No intervention was applied to the right hind leg.

The control group (n=7): After anesthesia, a tourniquet was applied to the right hind leg at the hip joint level. Before opening the tourniquet, the rats were given a total volume of 1 mL 0.9% NaCl via the tail vein. After three hours of ischemia, 24 hours reperfusion was applied and no treatment was administered. The Sgdx4 group (n=7): After anesthesia, a tourniquet was applied to the right hind leg at the hip joint level. Three hours of ischemia were applied. Immediately before opening the tourniquet, 4 mg/kg sugammadex (Bridion 200 mg/2 mL vial, Merck Sharp & Dohme) was administered via the tail vein in a total volume of 1 mL. Then 24 hours reperfusion was applied. The Sgdx16 group (n=7): After anesthesia, a tourniquet was applied to the right hind leg at the hip joint level. Three hours of ischemia were applied. Immediately before opening the tourniquet, 16 mg/kg sugammadex (Bridion 200 mg/2 ml vial, Merck Sharp & Dohme) was administered via the tail vein for a total volume of 1 mL. Then 24 hours reperfusion was applied. Doses of sugammadex were determined based on examples of doses used in previous studies with rats and healthy humans.[12,13] The rats were anesthetized with intraperitoneal (ip) 50 mg/kg ketamine (Ketalar flk., Pfizer Pharma GMBH, Germany) and 10 mg/kg xylazine hydrochloride (Alfazyne 2%, Alfasan International, Holland). A tourniquet was applied to the right hind leg to induce ischemia. Ketamine and xylazine doses were repeated every 45 minutes during the ischemia procedure.[5] A venous path was opened in the tail vein, and 5–10 mg/ kg/h physiological serum was administered to prevent dehydration. Cessation of blood flow was decided based on laser Doppler assessment of the femoral artery and at the end of the first, second, and third hour. After three hours of ischemia,[4,5] immediately before opening the tourniquet, 4 mg/ kg or 16 mg/kg sugammadex was administered via the tail vein. After administering sugammadex doses intravenously, the catheter was removed.

Animals were assigned to four groups. Except for the sham group, the three other groups had circumferential pressure applied to the groin of the right hind leg with an elastic bandage (1 cm width, 30 cm length) to induce lower extremity ischemia.5 Cessation of blood flow to the lower extremity of the animals was assessed using laser Doppler of the femoral artery at the end of the first, second, and third hour.

During the reperfusion period, animals had access to standard rat feed and water until two hours before the surgical procedure. At the end of 24-hour reperfusion, anesthesia was induced in the animals with ip 50 mg/kg ketamine (Ketalar flk., Pfizer Pharma GMBH, Germany) and 5–10 mg/kg xylazine hydrochloride (Alfazyne 2%, Alfasan International, Holland).

Experimental Groups

The right hind leg was dissected, and the gastrocnemius muscle was removed for histopathological investigation. Blood was removed by cardiac puncture for biochemical tests. At

The sham group (n=7): During this study, no other procedure 510

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this time, this study was ended, and the rats were sacrificed by exsanguination.

Biochemical Investigation For biochemical investigations, blood samples taken from the heart were assessed for serum CK (creatine kinase) and LDH (lactate dehydrogenase). Malondialdehyde (MDA) from serum and tissue samples and superoxide dismutase (SOD) from serum samples were manually measured using spectrophotometric methods. The serum was placed in biochemical tubes and stored at -80ºC until analysis. Before analysis, muscle tissues were weighed on a sensitive scale and placed in microcentrifuge tubes. During this process, samples were kept on ice and 800 mL PBS added to them. Tissues were homogenized in microcentrifuge tubes in a tissue lysis device for 180 seconds at 25/s frequency. The homogenate was centrifuged at 4ºC for 15 minutes at 13 000 g. After centrifuging, the uppermost supernatant was placed on ice with one portion stored for backup, while another portion was diluted to 1:8 with PBS and prepared for MDA analysis. Tissue and serum MDA levels were measured with a BioVision kit (Cat no: #K739-100, USA). The method involved forming an MDA-TBA complex between the MDA products in the sample and thiobarbituric acid, which was measured colorimetrically at 532 nm. The serum results were given as micromol/L, with tissue results given as micromol/gram protein and micromol/gram tissue. Tissue and serum SOD activity was measured using a BioVision kit (Cat no: #K335, USA). The method is based on the inhibition technique of superoxide anions of SOD in the sample; SOD activity is directly correlated with inhibition rate, and this is measured colorimetrically at 450 nm. Serum results are given as U/mL, with tissue results given as U/mg tissue and U/mg protein.

Histopathological Methods The gastrocnemius muscle tissues from each of the study groups were fixed for 48 hours in a 10% formaldehyde solu-

tion for light microscopy examination, and after fixation, they were washed in flowing water for 24 hours. The samples were passed through a series of increasing degrees of alcohol (80%, 96%, 100%) and dehydrated. Transparentized in xylene and was submerged in paraffin blocks.[14] The paraffin blocks were sliced into 5 μm sections using a fully automatic microtome (Leica RM 2255, Tokyo, Japan) and placed on light microscope slides. The sections were stained with hematoxylin-eosin (H-E) to observe and assess general histological structures.[15] They were also stained with Masson’s trichrome technique to differentiate better and investigate muscle and connective tissue.[16] The preparations obtained were assessed by an experienced histologist, blind to this study. Assessment of the muscle tissues was performed with an Olympus BX51 (Olympus, Tokyo, Japan) microscope. The findings were photographed at different scales using a camera attachment adapted to the light microscope (Olympus DP71; Olympus, Tokyo, Japan). For assessment of lineated muscle tissue, semi-quantitative scoring from 0–3 was assigned for disorganization of muscle fibers, degeneration, inflammatory cell infiltration, vascular congestion, and edema. The scoring for the semiquantitative assessment was 0 = normal, 1 = mild, 2 = moderate, and 3 = severe.[14]

Statistical Analysis For statistical analysis, the Statistical Package for the Social Sciences (SPSS) 15.0 program was used. Data with continuous values were shown as mean±SD. Analysis of data in the groups initially applied the Kolmogorov-Smirnov test and ShapiroWilk test to determine the distribution pattern of data. For data with continuous values, analysis of all groups used the Kruskal-Wallis tests, with the Mann-Whitney U test used for the 2-way analysis of groups. The Bonferroni correction was applied as a post-hoc correction. After the Bonferroni correction, a p-value <0.01 was accepted as statistically significant.

RESULTS When the groups were compared concerning histopathological results, there was a significant difference identified between the sham group and the control group for histopathological assessment parameters (p<0.01) (Table 1). Concerning

Table 1. Histological assessment of the groups Groups

Muscle degeneration

Inflammatory cells

Vascular congestion

Edema

Total score

Group Sham 0.85±0.37 0.57±0.53 0.85±0.37 0.42±0.53 2.71±1.11 Group Control

2.28±0.48* 2.42±0.53* 2.00±0.81* 1.85±0.37* 8.57±1.81*

Group Sgdx4

1.85±0.89

Group Sgdx16

2.57±0.53 2.85±0.37 2.28±0.75 1.57±0.53† 9.28±1.79† †

2.14±0.37‡ †

1.57±0.53

1.14±0.69 6.71±1.97‡

†

* p<0.01; Group Sham compared with Group Control; Mann-Whitney U test, Bonferroni correction. †p<0.01; Group Sham compared with Group Sgdx16 aMann-Whitney U test, Bonferroni correction. ‡p<0.01; Group Sham compared with Group Sgdx4; Mann-Whitney U test, Bonferroni correction.

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Table 2. Tissue and serum SOD and MDA values in the groups Groups Group Sham

SOD U/mg protein

SOD Blood (U/ml)

SOD U/mg tissue

MDA Mikromol/gr protein

MDA kan Mikromol/L

MDA Mikromol/gr tissue

8.23±1.85

12.05±0.39

0.74±0.11

4.24±1.23

5.98±2.19

0.38±0.09

Group Control

9.76±2.48

13.91±5.10

0.71±0.19

4.67±1.12

7.49±3.51

0.34±0.08

Group Sgdx4

11.32±4.07

11.73±0.41

0.80±0.25

4.79±1.55

10.60±11.89

0.35±0.13

Group Sgdx16

13.16±5.50

12.42±0.42

0.87±0.37

6.17±2.59

6.48±1.60

0.41±0.16

SOD: Superoxide dismutase; MDA: Malondialdehyde.

tion and degeneration in addition to normal striated muscle fibers.

Table 3. CK and LDH values in the groups Groups Group Sham

CK (IU/L)

LDH (IU/L)

530.71±118.44

746.85±311.90

Group Control

1722.85±494.94* 1219.00±416.65*

Group Sgdx4

739.71±233,70£ 871.28±319.18

Group Sgdx16

1005.42±395.74†€ 653.57±282.70€

CK: Creatine kinase; LDH: Lactate dehydrogenase. *p<0.01; Group Sham compared with Group Control; Mann-Whitney U test, Bonferroni correction. †p<0.01; Group Sham compared with Group Sgdx16; Mann-Whitney U test, Bonferroni correction. £p<0.01; Group Control compared with Group Sgdx4; Mann-Whitney U test, Bonferroni correction. €p<0.01; Group Control compared with Group Sgdx16; Mann-Whitney U test, Bonferroni correction.

SOD and MDA values obtained from serum and tissue samples, there was no significant difference found between the sham group and the control group (p>0.01) (Table 2). There was a significant difference between the sham and control groups for muscle enzyme levels (p<0.01) (Table 3). When the groups given the study drug were assessed, apart from inflammatory cell inflammation (p<0.01) in the Sgdx4 group, there were no significant differences for other histopathological assessment parameters compared to both the sham and control groups (p>0.01). There was a significant difference identified concerning histopathological assessment parameters between the Sgdx16 group and the sham group (p<0.01) (Table 1). There were significant differences between the Sgdx4 group and Sgdx16 group (which had received the study drug), and the control and sham groups concerning muscle enzyme levels (p<0.01) (Table 3). There were no statistically significant differences found for SOD and MDA values obtained from serum and tissue samples for any group (p>0.01) (Table 2). Evaluation of striated muscle tissue showed normal striated muscle structure in the sham group. Muscle fibers were regularly arranged. The transverse lineations in muscle fibers had normal morphology (Fig. 1a). Assessment of muscle tissue in the control group showed widespread disorganiza512

There were openings between muscle fibers, widespread inflammatory cell infiltration, and vascular congestion (Fig.1b). Evaluation of muscle tissue in the Sgdx4 group showed openings between muscle fibers and occasional degeneration of muscle fibers. We observed vascular congestion between muscle fibers and widespread inflammatory cell infiltration (Fig. 1c). Muscle tissue evaluation of the Sgdx16 group found widespread muscle fiber disorganization, degeneration, and openings between muscle fibers. There was vascular congestion between muscle fibers and widespread inflammatory cell infiltration (Fig. 1d). Staining with the Masson’s trichrome technique allowed clear observations to be made (Fig. 2 a-d).

DISCUSSION Using the I/R model induced by applying a tourniquet to the lower extremity of rats, we aimed to assess the histopathological and biochemical effects of 4 mg/kg and 16 mg/kg intravenous doses of sugammadex on skeletal muscle I/R injury. We found that I/R injury was prevented in the 4 mg/kg sugammadex group concerning inflammatory cell formation, pO2, and pCO2; however, the 16 mg/kg dose was not effective. The injury that arises from I/R and linked to tourniquet use occurs due to functional and metabolic changes in the vascular bed and muscle tissue. There is a correlation between the degree of local and systemic effects occurring after tourniquet use and the inflammation duration. Concerning morphology and histochemistry, the degree of injury varies linked to the duration of tourniquet use.[4] There is a significant link between the ischemic injury and the duration of ischemia. In a lower extremity I/R study, Petrasek et al.[17] identified that by the fourth hour of ischemia, the necrosis rate in muscle tissue was 21%; by the fifth hour, it was 61%, and after the fifth hour, it was 92%. Blaisdell et al.[4] showed that after three hours of lower extremity ischemia, irreversible histological injury began in muscle tissue and was complete by the sixth hour. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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(a)

(b)

(c)

(d)

Figure 1. Photomicrograph of lineated muscle tissue (H&E X 200). (a) Sham Group, (b) Control Group, (c) Sgdx4 Group, (d) Sgdx16 Group. Normal lineated muscle cell (→), degenerated lineated muscle cell (↑), inflammatory cell infiltration (∆), vascular congestion (star).

(a)

(b)

(c)

(d)

Figure 2. Photomicrograph of lineated muscle cell (Massın trichrome X 200). (a) Sham Group, (b) Control Group, (c) Sgdx4 Group, (d) Sgdx16 Group. Normal lineated muscle cell (→), degenerated lineated muscle cell (↑), inflammatory cell infiltration (∆), vascular congestion (star).

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Duru et al.[5] demonstrated widespread neutrophil accumulation in muscle tissue after three hours of ischemia in rats. In light of these studies, for our experiments, we chose the beginning of irreversible injury (at three hours) for the duration of ischemia. When the sham group and the control group were compared at the end of three hours ischemia, there was a statistically significant difference concerning muscle degeneration, inflammatory cells, vascular congestion, and edema formation. Carmo-Araújo et al.[18] in a study with four hours ischemia (I/R), four hours ischemia plus one-hour reperfusion (I/R1hr), four hours ischemia plus 24 hours reperfusion (I/R24hr), and four hours ischemia plus 72 hours reperfusion (I/R-72hr) determined that the lesions in muscle samples showed a proportional increase to the reperfusion duration. [18] In our study, we evaluated three hours ischemia, followed by a 24-hour reperfusion duration. In previous studies, many agents, such as colchicine,[19] tramadol,[20] silibinin,[21] iloprost,[22] and alpha-tocopherol,[23] have been shown to be beneficial for the amelioration of muscle ischemia-reperfusion injury linked to tourniquet use. In situations where I/R injury occur, it may be related to a variety of operations and surgeries. In these situations, the efficacy of the anesthetic agents used against I/R injury gains importance. Agents commonly used in anesthesia practice have been shown to have protective effects against muscle I/R injury, but scientific studies of the new generation of agents are limited, and sugammadex is such an agent. Sugammadex is the first neuromuscular reversal agent with a modified gammacyclodextrin structure to be developed.[24] Sugammadex was designed to reverse the effects of neuromuscular blockers with aminosteroid structure, such as rocuronium and vecuronium, commonly used in general anesthesia.[25] Sugammadex reduces the amounts of rocuronium and vecuronium binding to nicotinic receptors at the neuromuscular junction, and the block occurring at the neuromuscular junction is reversed.[26] The doses of sugammadex used for humans are 2.0 mg/kg, 4.0 mg/kg, and 16 mg/kg. A sugammadex dose of 16 mg/kg may cause a metallic, bitter taste in the mouth; however, no dose-linked, serious side effects have been encountered. It is recommended that sugammadex not be used for patients with severe renal failure.[27] There has also been a study assessing sugammadex in a global cerebral hypoxia model induced in rats.[11] This study by Ozbilgin et al.[11] involved 10 minutes of global cerebral ischemia in rats followed by 24-hour reperfusion and used 16 mg/kg 514

and 100 mg/kg doses of sugammadex. According to the immunohistochemical assessment of tissue samples from the hippocampus and parietal cortex of the treatment groups, TUNEL results and caspase values were lower than in the cerebral I/R group. In addition, Ozbilgin et al.[11] showed that a high dose of sugammadex was more neuroprotective and that a high dose of sugammadex had an antioxidant effect. In our study, we used 4 mg/kg and 16 mg/kg doses to observe the effects of sugammadex on muscle I/R injury. Iriz et al.[28] evaluated the antioxidant and cytoprotective effects of iloprost and Vitamin C in a distant organ after abdominal aortic ischemia-reperfusion injury. SOD, MDA and catalase were evaluated in myocardial tissue samples. Oxidative stress markers were significantly lower in iloprost and iloprost + vitamin C groups. Myocardial damage and mitochondrial morphology changes were significantly lower on electron microscopy imaging of myocardial tissue. Iriz et al.[28] reported that myocardial damage and edema occurred after ischemia-reperfusion of the abdominal aorta and that groups treated with iloprost and iloprost + vitamin C weakened the reperfusion injury of distant organs. Takhtfooladi et al.,[20] in the rat skeletal muscle I/R model with a 2-hour clamp on the femoral artery, followed by reperfusion for 24 hours after the reperfusion of gastrocnemius muscle tissue and blood samples compared to the ischemia group significantly lower values of the group given tramadol, SOD values were found to increase significantly. In another study, Ergün et al.[21] with different doses of cilibiline (50, 100, 200 mg/kg) in the rat skeletal muscle I R model ischemia three hours after two hours reperfusion in all doses of cilibiline tissue MDA values were statistically significant difference compared to the ischemia group. SOD values could not find any difference. In our study, there was no significant difference between MDA values. The difference in MDA values may be due to differences in ischemia and reperfusion times, or lack of attention to the cold chain during storage or transfer of the MDA kit. Because in our histological evaluation, there was a significant difference in muscle degeneration, vascular congestion, inflammatory cell and edema formation in the control group compared to the sham group. From this point of view, we do not think that there is a tourniquet-induced problem in our rat skeletal muscle I/R model. Concerning SOD values, only 16 mg/kg and 4 mg/kg groups were significantly different. We determined that there was no difference in muscle enzyme levels and histopathological findings between the SGDx4 group and the sham group and that there was a protective effect, but the SGDx16 group did not have an I/R damaging effect. We determined our doses based on the doses Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Alagöz et al. Effects of sugammadex on ischemia reperfusion in a rat extremity model

used in previous animal experiments and in current clinical administration. As 16 mg/kg sugammadex is the highest dose for use in anesthesia administration, we chose this dose.[11–13] In a previous study in cerebral ischemia and reperfusion injury, an increased sugammadex dose was found to be related to increasing efficacy.[11] While our study showed a significant difference between the control and sham groups concerning microscopic investigation of skeletal muscle, histopathological scores for skeletal muscle, and skeletal muscle enzyme levels, we did not find any significant difference in tissue and serum MDA and SOD values between any group; this may be due to missing the peak periods concerning MDA and SOD levels. A limitation of our study is that our study does not include any detailed data related to the mechanism or causes of the difference in response curves. Another limitation of our study is that despite using the ischemia/reperfusion duration used in previous studies, a 24-hour reperfusion period may have missed the peak period of reperfusion injury. We hypothesized that, similar to our previous study,[11] the increasing dose would lead to increased efficacy. However, surprisingly, in this study, increased dose did not increase efficacy. To ensure a better interpretation of these topics following this initial study using sugammadex for I/R injury, we recommend that more in-depth studies should be completed. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.A., S.K.; Design: A.A., V.H.; Supervision: A.A., N.B.; Materials: N.B., V.H.; Data: A.A., N.B.; Analysis: V.H., E.Y., A.R.Ş.; Literature search: A.A., N.B.; Writing: A.A., E.Y., A.R.Ş.; Critical revision: A.A., V.H. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Gute DC, Ishida T, Yarimizu K, Korthuis RJ. Inflammatory responses to ischemia and reperfusion in skeletal muscle. Mol Cell Biochem 1998;179:169–87. 2. Koksal C, Bozkurt AK, Sirin G, Konukoglu D, Ustundag N. Aprotinin ameliorates ischemia/reperfusion injury in a rat hind limb model. Vascul Pharmacol 2004;41:125–9. 3. Hobson RW 2nd, Neville R, Watanabe B, Canady J, Wright JG, Belkin M. Role of heparin in reducing skeletal muscle infarction in ischemiareperfusion. Microcirc Endothelium Lymphatics 1989;5:259–76. 4. Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002;10:620–30.

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5. Duru S, Koca U, Oztekin S, Olguner C, Kar A, Coker C, et al. Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of bilateral lower limb ischemia and reperfusion: a pilot study. Acta Anaesthesiol Scand 2005;49:1142−8. 6. Dammers R, Wehrens XH, oude Egbrink MG, Slaaf DW, Kurvers HA, Ramsay G. Microcirculatory effects of experimental acute limb ischaemia-reperfusion. Br J Surg 2001;88:816–24. 7. Rivers JR, Maggo SD, Ashton JC. Neuroprotective effect of hydroxypropyl-β-cyclodextrin in hypoxia-ischemia. Neuroreport 2012;23:134– 8. 8. Frank C, Rufini S, Tancredi V, Forcina R, Grossi D, D’Arcangelo G. Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus. Exp Neurol 2008;212:407–14. 9. Rufini S, Grossi D, Luly P, Tancredi V, Frank C, D’Arcangelo G. Cholesterol depletion inhibits electrophysiological changes induced by anoxia in CA1 region of rat hippocampal slices. Brain Res 2009;1298:178–85. 10. Palanca JM, Aguirre-Rueda D, Granell MV, Aldasoro M, Garcia A, Iradi A, et al. Sugammadex, a neuromuscular blockade reversal agent, causes neuronal apoptosis in primary cultures. Int J Med Sci 2013;10:1278−85. 11. Ozbilgin S, Yılmaz O, Ergur BU, Hancı V, Ozbal S, Yurtlu S, et al. Effectiveness of sugammadex for cerebral ischemia/reperfusion injury. Kaohsiung J Med Sci 2016;32:292−301. 12. Hogg RM, Mirakhur RK. Sugammadex: a selective relaxant binding agent for reversal of neuromuscular block. Expert Rev Neurother 2009;9:599–608. 13. Peeters PA, van den Heuvel MW, van Heumen E, Passier PC, Smeets JM, van Iersel T, et al. Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study. Clin Drug Investig 2010;30:867−74. 14. Erkanli K, Kayalar N, Erkanli G, Ercan F, Sener G, Kirali K. Melatonin protects against ischemia/reperfusion injury in skeletal muscle. J Pineal Res 2005;39:238–42. 15. Stevens A, Wilson I. The haematoxylin and eosin. In: Bancroft JD, Stevens A, editors. Theory and Practice of Histological Techniques. 4th edition: Churchill Livingstone;1996.p.99. 16. Bradbury P, Rae K. Connective tissues and stains. In: Bancroft J, D.Stevens A, editors. Theory and Practice of Histological Techniques. 4th edition. Churchill Livingstone; 1996.p.125−9. 17. Petrasek PF, Homer-Vanniasinkam S, Walker PM. Determinants of ischemic injury to skeletal muscle. J Vasc Surg 1994;19:623–31. 18. Carmo-Araújo EM, Dal-Pai-Silva M, Dal-Pai V, Cecchini R, Anjos Ferreira AL. Ischaemia and reperfusion effects on skeletal muscle tissue: morphological and histochemical studies. Int J Exp Pathol 2007;88:147– 54. 19. Wang L, Shan Y, Chen L, Lin B, Xiong X, Lin L, et al. Colchicine protects rat skeletal muscle from ischemia/reperfusion injury by suppressing oxidative stress and inflammation. Iran J Basic Med Sci 2016;19:670−5. 20. Takhtfooladi HA, Takhtfooladi MA, Karimi P, Asl HA, Mobarakeh SZ. Influence of tramadol on ischemia-reperfusion injury of rats’ skeletal muscle. Int J Surg 2014;12:963–8. 21. Ergün Y, Üremiş M, Kılınç M, Alıcı T. Antioxidant effect of Legalon(r) SIL in ischemia-reperfusion injury of rat skeletal muscle. Acta Cir Bras 2016;31:264–70. 22. Bozkurt AK. Alpha-tocopherol (Vitamin E) and iloprost attenuate reperfusion injury in skeletal muscle ischemia/reperfusion injury. J Cardiovasc Surg (Torino) 2002;43:693–6. 23. Silva MG, Castro AA, Ramos EA, Peixoto E, Miranda F Jr, Pitta Gde B, et al. Histological and biochemical serum effects of alpha-tocopherol on ischemia/reperfusion-related injuries induced in the pelvic limb of rats. Acta Cir Bras 2005;20:375−81. 24. Bom A, Bradley M, Cameron K, Clark JK, Van Egmond J, Feilden H, et

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thesiology?. Anesth Analg 2007;104:477–8. 27. Hogg RM, Mirakhur RK. Sugammadex: a selective relaxant binding agent for reversal of neuromuscular block. Expert Rev Neurother 2009;9:599–608. 28. Iriz E, Iriz A, Take G, Ozgul H, Oktar L, Demirtas H, et al. Iloprost and vitamin C attenuates acute myocardial injury induced by suprarenal aortic ischemia-reperfusion in rabbits. Bratisl Lek Listy 2015;116:627−31.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçan ekstremite modelinde iskemi reperfüzyon üzerine sugammadeks’in etkisi Dr. Ali Alagöz,1 Dr. Semih Küçükgüçlü,2 Dr. Nilay Boztaş,2 Dr. Volkan Hancı,2 Dr. Esin Yuluğ,3 Dr. Ali Rıza Şişman4 Foça Devlet Hastanesi, Anesteziyoloji Kliniği, İzmir Dokuz Eylül Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İzmir 3 Karadeniz Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Trabzon 4 Dokuz Eylül Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, İzmir 1 2

AMAÇ: Çalışmamızın hipotezi, sugammadeks’in sıçanlarda iskemi reperfüzyon (İ/R) hasarına karşı koruyucu etkinliğe sahip olmasıdır. GEREÇ VE YÖNTEM: Çalışmaya 28 erkek Wistar Albino sıçanı dahil edildi. Sıçanlar dört gruba ayrıldı. Sham grubuna anestezi uygulaması dışında bir girişim uygulanmadı. Kontrol grubuna 3 saat iskemi ve 24 saat reperfüzyon uygulandı. Sgdks4 grubu ve Sgdks 16 grubu, intravenöz olarak sırasıyla 4 mg/kg ve 16 mg/kg sugammadeks aldı ve ardından reperfüzyon uygulandı. Histopatolojik inceleme ve serum kreatin kinaz (CK), laktat dehidrojenaz (LDH), serum ve doku malondialdehid (MDA) ve süperoksit dismutaz (SOD) analizleri yapıldı. BULGULAR: Sham grubu ve kontrol grubu karşılaştırıldığında, histopatolojik olarak istatistiksel olarak anlamlı farklılıklar vardı (p<0.01). Sgdks4 grubu ile sham ve kontrol grupları arasında histopatolojik olarak anlamlı fark yoktu (p>0.01). Sgdks16 grubu ile sham grubu arasında histopatolojik olarak anlamlı bir fark vardı (p<0.01). Sham ve kontrol grupları arasında CK ve LDH düzeyleri açısından anlamlı fark vardı (p<0.01). Kontrol grubu ile Sgdks4 grubu arasında CK düzeyleri arasında ve kontrol grubu ile Sgdks16 grubu arasında CK ve LDH düzeylerinde anlamlı bir fark vardı (p<0.01). TARTIŞMA: Çalışmamızda, sıçanlarda tek taraflı alt ekstremite İ/R yaralanması üzerine 4 mg/kg sugammadeks’in histolojik ve biyokimyasal koruyucu etkileri incelendi. 4 mg/kg sugammadeks dozunun 16 mg/kg dozdan daha etkili olduğunu görüldü. Anahtar sözcükler: Alt ekstremite; iskemi; reperfüzyon; sugammadeks. Ulus Travma Acil Cerrahi Derg 2020;26(4):509-516

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doi: 10.14744/tjtes.2019.12524

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EXPERIMENTAL STUDY

The effects of specific and non-specific phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress and remote organ injury in two-hit trauma model Özdemir Özer, M.D.,1

Uğur Topal, M.D.,2

Metin Şen, M.D.1

Departmant of General Surgery, Cumhuriyet Universitiy Faculty of Medicine, Sivas-Turkey

Departmant of Surgical Oncology, Erciyes University Faculty of Medicine, Kayseri-Turkey

ABSTRACT BACKGROUND: Sepsis is a systemic inflammatory response to infection and is one of the leading causes of morbidity and mortality. The second hit after trauma causes increased inflammatory response and multiple organ failure (MOF). The infection which develops after burn injury is a suitable model for a two-hit trauma study. Sepsis causes the release of biochemical mediators, such as Free Oxygen Radicals (FORs), which may lead to lipid peroxidation, which may play a key role in multiple organ failure. In this study, we aimed to investigate the effects of phosphodiesterase (PDE) inhibitors (sildenafil, milrinone, pentoxifylline) and N-acetylcysteine (NAS) on oxidative stress and organ damage in two-hit models. METHODS: In this experimental study, peritonitis was created by cecal ligation and puncture (CLP) method in 40 rats, 72 hours after creating a 30% scalding injury. Rats were divided into five groups of eight rats each as follows: Group I: No treatment; Group II: 10/mg/ kg/day dosage of intraperitoneal (i.p) sildenafil treatment was applied for 72 hours after CLP; Group III: 1/mg/kg/day dosage of i.p milrinone treatment was applied for 72 hours after CLP; Group IV: 150/mg/kg/day dosage of i.p NAS treatment was applied for 72 hours after CLP; Group V: 50/mg/kg/day dosage of i.p pentoxifylline treatment was applied for 72 hours after CLP. All rats were sacrificed on the seventh day of this study. Malondialdehyde (MDA), Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), catalase, Tumor Necrotic Factor-alpha (TNF-α) levels, and tissue (lung, kidney) and serum samples were taken for histopathological study. RESULTS: When compared to the control group, the tissue damage score was found to be lower in all treatment groups. Sildenafil, milrinone and NAS groups had higher kidney GPx levels compared to the control group. Milrinone and pentoxifylline were higher in the lung tissue compared to the SOD control group. TNFα levels were lower in pentoxifylline and milrinone groups compared to the control group. CONCLUSION: This experimental study has shown that PDE inhibitors and NAS have a decreasing effect on oxidative stress and distant organ damage in the two-hit model. Further clinical and experimental studies are needed on this subject. Keywords: Antioxidant; free oxygen radicals; tissue damage; phosphodiesterase inhibitor; sepsis.

INTRODUCTION Sepsis is a systemic infectious disease that may lead to shock, organ failure, and death and should be treated urgently.[1] In the presence of endotoxin, oxygen decreases in hypoxic and acidic environments, and free oxygen radicals (FOR) are formed; activation of leukocytes may also lead to FOR production.[2]

The occurrence of the second hit in trauma patients causes the inflammatory response to exacerbate and leads to the development of multiple organ damage. Infection after burn injury is a suitable model for two-hit trauma studies.[3] Systemic inflammatory response syndrome (SIRS), which develops in some patients with the burn or severe trauma, may directly lead to early multi-organ failure.[4]

Cite this article as: Özer Ö, Topal U, Şen M. The effects of specific and non-specific phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress and remote organ injury in two-hit trauma model. Ulus Travma Acil Cerrahi Derg 2020;26:517-525. Address for correspondence: Özdemir Özer, M.D. Erciyes Üniversitesi Tıp Fakültesi Hastaneleri, Genel Cerrahi Anabilim Dalı, Kat 6, Kayseri, Turkey Tel: +90 352 - 207 66 66 E-mail: drdemir2014@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):517-525 DOI: 10.14744/tjtes.2019.00570 Submitted: 08.02.2019 Accepted: 09.11.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Initial trauma (e.g., hemorrhagic shock, ischemia-reperfusion injury, burn) leads to the emergence of an abnormal immune or inflammatory response which brings about a potential secondary trauma (e.g., infection), it is said that the occurrence of a second hit leads to an exaggerated systemic inflammatory response.[5] These inflammatory changes are called the “two-hit trauma” hypothesis. Post-traumatic opportunistic infections that would not normally be mortal may cause serious SIRS and late MOF development in critically ill patients and these findings support the two-hit hypothesis.[6] Many different models with consecutive traumas were used to create two-hit trauma models. Infection following burn injury is one of the most common trauma models in the clinic. In the literature, two-hit trauma models created by the application of CLP and intraperitoneal endotoxin after burn trauma were studied.[5–7] In this study, a CLP after-burn model was chosen to create a two-hit trauma model. In this study, the effects of NAS and PDE inhibitors (pentoxifylline, sildenafil, milrinone) on oxidative stress and distant organ damage are investigated in twohit trauma models consisting of sequential burn and sepsis

MATERIALS AND METHODS This study was carried out in Cumhuriyet University Experimental Research and Animal Laboratory. The permission was obtained from Cumhuriyet University Ethics Committee dated 23.07.2012-335. Forty Wistar Albino rats weighing 180–250 grams were used in this study. Rats were fed with standard rat feed. They were fasted for 12 hours before the operation but allowed to drink water.

Experiment Protocol The animals were divided into five groups, each containing eight rats. A 3x4 cm area of the back of all rats was shaved. A third-degree 30% scald burn was performed, and 72 hours later, peritonitis was induced by the CLP method.

ing a thermometer. The rats received no treatment for their burn injury during the experiment (Fig. 1).

CLP Model A midline laparotomy was performed under general anesthesia. After the cecum was isolated, the ileocecal valve was ligated with 3/0 silk underneath. The cecum was perforated from two separate points by a 22 Gauge needle and was then slightly stroked, and intraperitoneal feces contamination was achieved. 4 ml of saline was given subcutaneously to the back area for resuscitation and the abdominal wall was closed in two layers (Figs. 2a-c). Animals were divided into five groups, each containing eight rats: Group I: No treatment; Group II: 10/mg/kg/day dosage of intraperitoneal (i.p) sildenafil treatment was applied for 72 hours after CLP; Group III: 1/mg/kg/day dosage of i.p milrinone treatment was applied for 72 hours after CLP; Group IV: 150/mg/kg/day dosage of i.p NAS treatment was applied for 72 hours after CLP; Group V: 50/mg/kg/day dosage of i.p pentoksifilin treatment was applied for 72 hours after CLP. All rats were sacrificed on the seventh day of this study, under general anesthesia. Laparotomy was performed on the sacrificed rats, and lung and kidney tissue samples were obtained for the histopathological study and the determination of tissue MDA, GPX, SOD, catalase and TNF-α levels. The same biochemical parameters were also studied from serum samples taken from rats. 5 ml of blood was collected with intracardiac technic.

Anesthesia General anesthesia was applied to all groups. For this purpose, a mixture of intramuscular 5 mg/kg xylazine (Rompun®) and 30 mg/kg ketamine hydrochloride (Ketalar®) was used. The burn model, CLP model and sacrifice were all made under general anesthesia.

Burn Model Under general anesthesia, a 3x4 cm area representing 30% of the body surface was shaved in the dorsal region of the animals. The remaining body parts were placed in previously prepared molds, leaving the shaved area out. The shaved area was kept in 96C water for 12 seconds to obtain a third-degree standard burn. Water temperature was measured us518

Figure 1. The shaved area was kept in 96°C water for 12 seconds and a third degree standard burn was obtained

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(a)

(b)

(c)

Figure 2. (a) The cecum was perforated from two separate points by a 22 Gauge needle, and was then slightly stroked and intraperitoneal feces contamination was achieved. 4 ml of saline was given subcutaneously to the back area. (b) The cecum was perforated from two separate points by a 22 Gauge needle, and was then slightly stroked and intraperitoneal feces contamination was achieved. 4 ml of saline was given subcutaneously to the back area. (c) The cecum was perforated from two separate points by a 22 Gauge needle, and was then slightly stroked and intraperitoneal feces contamination was achieved. 4 ml of saline was given subcutaneously to the back area.

Histopathological Study Tissues harvested for histopathological examination were fixed in 10% buffered formalin solution. The fixated tissues were monitored according to known methods and blocked in paraffin. Serial sections of 5 μm thick paraffin blocks were stained with Hematoxylin Eosin and examined under a light microscope. The evaluation of pathological lesions was done according to the following scores; edema in the lung tissue 1 point, hyperemia 1 point, thickening in intra-alveolar septum 2 points, mononuclear cell infiltration 2 points, shedding alveolar epithelium 3 points, hemorrhage 3 points; hyperemia in kidney tissue 1 point, mesangial cell hyperplasia in glomerulus 2 points, expansion in glomerular space 1 point, degeneration in tubular epithelium 2 points, necrosis in tubular epithelium 3 points, mononuclear cell infiltration 2 points, hemorrhage 3 points.

Study Methods of Biochemical Parameters MDA (nm/mg) was measured spectrophotometrically by a method modified from Satoh and Yagi.[8] Superoxide dismutase enzyme was determined by the method modified by Sun et al.[9] Glutathione peroxidase activity was studied according to the method of Paglia et al.[10] Catalase activity was measured by the Aebi method.[11] TNF-α was determined by the single-step sandwich ELISA (TNF-α Trousse De Dosage Immunoennzymatique Immunoassay Kit, Immunoech, France) method.

Statistical Analysis All data were given as mean ± standard error of the mean (SEM). Statistical analysis was performed using SPSS 11.5 program. Kruskal-Wallis test was used to evaluate statistical differences between independent groups, and Mann-Whitney Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

U test was used for the comparison of groups. P<0.05 was considered statistically significant.

RESULTS A total of five rats, one rat in the control group, two rats in the milrinone and two rats in the NAS groups, died during the experiment period. All deaths occurred within the first 72 hours after the burn. The dead rats were not replaced by new rats. There was no statistically significant difference between the groups concerning mortality. Tissue and serum malondialdehyde levels and the distribution of MDA values measured in lung, kidney tissues and serum are shown in Table 1. When MDA levels were compared based on organs in all groups, the difference in lung and kidney tissues were found to be statistically significant (p=0.000 for lung; and 0.01 for kidney). MDA levels in the lung tissue was significantly higher in milrinone, NAS and pentoxifylline groups compared to the control group (p=0.007, p=0.015, p=0.001, respectively). Table 1. MDA (nmol/mg) distribution of tissue and serum levels by groups

Lung Kidney Serum MDA value MDA value MDA value

Control

0.060±0.018 0.223±0.077 0.6±0.2

Sildenafil

0.081±0.049 0.298±0.082 0.6±0.2

Milrinon

0.124±0.047 0.582±0.499 0.7±0.4

NAS

0.170±0.066 0.124±0.030 1.0±0.5

Pentoxyfilin 0.327±0.094 0.303±0.206 0.4±0.2 P value

0.000

0.010

0.093

* The values in the table are shown as mean±standard deviation. MDA: Malondialdehyde; NAS: N-acetylcysteine.

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Table 2. GPX (U/mg) distribution of tissue and serum levels by groups

Table 3. Distribution of SOD (U/mg protein) tissue and serum levels by groups

Lung Kidney Serum GPx value GPx value GPx value

Lung Kidney Serum SOD value SOD value SOD value

Control

0.184±0.037 0.055±0.022 1.1±0.7

Control

1.567±0.604 1.126±0.102 11.5±2.1

Sildenafil

0.206±0.080 0.267±0.058 1.0±0.4

Sildenafil

1.530±0.673 1.446±0.647 10.6±3.5

Milrinon

0.279±0.091 0.148±0.055 0.9±0.5

Milrinon

2.353±0.407 1.293±0.380 7.9±3.4

NAS

0.311±0.062 0.166±0.014 1.3±0.3

NAS

2.146±0.521 1.184±0.133 7.5±4.2

Pentoxyfilin 0.157±0.121 0.127±0.077 1.4±0.4

Pentoxyfilin 2.259±0.471 1.343±0.184 11.4±1.8

P value

0.021

0.000

0.436

* The values in the table are shown as mean±standard deviation. GPx: Glutathione Peroxidase; SOD: Superoxide Dismutase; NAS: N-acetylcysteine.

MDA decreased in the lung tissue in the sildenafil group more than all other groups and in the binary comparisons conducted; in the lung tissue, sildenafil group showed a significant decrease when compared to the NAS group (p=0.039) and pentoxyphyllin group (p=0.001). No significant difference was observed between the groups concerning MDA serum levels. Table 2 shows the distribution of tissue and serum glutathione peroxidase levels between the groups and GPx values measured in the lung, kidney tissues and serum. The difference in the increase in GPX levels was found to be significant in the lung and kidney tissues compared to all groups (p=0.021 for lung; p=0.000 for kidney). Bilateral comparisons showed significantly higher levels of milrinone and NAS groups in lung tissue than the control group (p=0.046, p=0.004, respectively). Sildenafil, milrinone and NAS groups were significantly increased in kidney tissue compared to the control group (p=0.001, p=0.022, p=0.003, respectively). In addition, the increase in the sildenafil group in kidney tissue was significantly higher than milrinone, NAS and pentoxifylline groups (p=0,005, p=0,002, p=0,003, respectively). No significant difference was observed between the groups concerning GPX serum levels. Table 3 shows the distribution of SOD values between the groups, and SOD levels in lung, kidney tissue and serum. The difference in the change of SOD levels was found to be significant in the lung tissue among all groups (p=0.03). In the comparisons with the control group, the SOD value of the milrinone and pentoxifylline groups were significantly higher in the lung tissue (p=0.032, p=0.049, respectively). It was significantly higher in the pentoxifylline group than the control group in the kidney tissue (p=0.025). SOD serum levels were not significantly different between groups. The distribution of tissue and serum catalase levels, catalase values in the lungs, kidney tissues and serum are given in Table 4. Kidney tissue levels were found to be significantly lower in the pentoxyfylline group compared to the control group (p=0.018). Catalase serum levels were not significantly different between groups. 520

0.034

0.243

0.307

* The values in the table are shown as mean±standard deviation. SOD: Superoxide Dismutase; NAS: N-acetylcysteine.

Table 4. Catalase (k/g) distribution of tissue and serum levels by groups

Lung Kidney Serum Catalase Catalase Catalase value value value

Control

41.557±70.382 14.214±4.984

Sildenafil Milrinon NAS

0.0±0.0

2.938±2.190 15.800±4.646 0.0±0.0 40.283±83.395 12.450±8.225

0.0±0.0

5.767±2.915 16.117±12.028 0.0±0.0

Pentoxyfilin 9.100±11.999 6.800±3.894 0.0±0.0 P value

0.319

0.082

0.562

* The values in the table are shown as mean±standard deviation. NAS: N-acetylcysteine.

Table 5. Distribution of TNF-a tissue and serum levels by groups

Lung Kidney Serum TNF-a value TNF-a value TNF-a value

Control Sildenafil Mİlrinon NAS

104.100±41.417 755.114±57.571 0.0±0.0 91.275±20.448 544.250±249.469 0.0±0.0 194.367±278.229 445.883±263.447 0.0±0.0 77.267±12.232 736.650±112.953 0.0±0.0±

Pentoxyfilin 69.350±31.202 457.029±150.208

0.0

P value

1.00

0.228

0.016

* The values in the table are shown as mean±standard deviation. NAS: N-acetylcysteine. TNF-α: Tumor Necrotic Factor alpha.

The distribution of tissue and serum TNF-a levels among groups and TNF-α values measured in lung, kidney and serum are shown in Table 5. In the kidney tissue, milrinone and penthoxyfylline groups were significantly lower than the control group (p=0.046, p=0.002, respectively). No significant difference was observed in TNF-a serum levels between the groups. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Özer et al. The effects of phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress in two-hit trauma model

Table 6. Distribution of histopathological damage score by groups Lung Kidney Pathologic score Pathologic score Control 9.4±1.0 10.0±1.2 Sildenafil 4.6±1.4 4.8±1.3 Milrinon 5.1±2.0 5.1±1.5 NAS

5.6±2.1 5.1±1.5

Pentoxyfilin 7.3±1.3 P value

0.000

8.4±2.1 0.000

*The values in the table are shown as mean±standard deviation. NAS: N-acetylcysteine.

The histopathological findings and the distribution of histopathological damage score values between the groups in the lung and kidney tissues are shown in Table 6. When the comparison of renal tissue damage scores was made, pathological damage was significantly lower in sildenafil, milrinone

Figure 3. Histopathological damage developed in kidney tissue (A) Control group: Severe hyperemia (star), necrosis in tubule epithelia (red arrows) and expansion in the glomerular space (white arrow). (B) Sildenafil group: Mild expansion of glomerular spaces (white).

(a)

(b)

and NAS groups compared to the control group (p=0.001, p=0.001, p=0.001, respectively). The pathological damage score of all groups was significantly lower than the control group for the lung tissue (sildenafil, milrinone, NAS and pentoxyfylline, p=0.001, p=0.001, p=0.002, p=005, respectively). Histopathological damage developed in kidney tissue (A) Control group: Severe hyperemia (star), necrosis in tubule epithelia (red arrows) and expansion in the glomerular space (white arrow). (B) Sildenafil group: Mild expansion of glomerular spaces (white arrow) (Fig. 3). Histopathological damage developed in lung tissue (A) Control group: Thickening of interalveolar septum and severe hyperemia (arrrows). (B) NAS group: Thickening of interalveolar septum and severe hyperemia (arrows). (C) Milrinone group: edema fluid in alveol lumens (white arrows), mild thickening of interalveolar septum (black arrows) (Fig. 4a-c).

DISCUSSION Two-hit trauma models are known to be effective in the development of systemic complications, such as post-traumatic respiratory failure syndrome.[12,13] Common components of sepsis, such as increased lactate level, thrombocytopenia and hyperdynamic-hypodynamic shock, are observed more densely in the experimental twohit trauma model.[14] In the two-hit models with CLP after a burn injury, it was shown that the first trauma (burn) caused a decrease in resistance to peritoneal sepsis in experimental animals and the mortality increased.[7] In this model, the second trauma causes maximum mortality after the seventh day of burn injury alone. This finding is consistent with clinical information indicating that infection resistance in burn patients is very low after one week.[7,15,16] In other studies in the literature, it was shown that the second hit performed by giving intraperitoneal endotoxin in experimental animals with burn trauma, increased Toll-like receptor-4, IL-1β, TNFα and IL-6 levels.[5,6] Similarly, neutrophil infiltration increases in the lung and liver.[5] CLP-induced polymicrobial sepsis model is the most similar model to the progression and characteristic

(c)

Figure 4. Histopathological damage developed in lung tissue (a) Control group: Thickening of interalveolar septum and severe hyperemia (arrrows). (b) NAS group: Thickening of interalveolar septum and severe hyperemia (arrows). (c) Histopathological damage developed in lung tissue Milrinon group: edema fluid in alveol lumens (white arrows), mild thickening of interalveolar septum (black arrows).

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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Özer et al. The effects of phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress in two-hit trauma model

of sepsis in humans. The CLP model is now considered the gold standard for the experimental sepsis model.[17] In clinical and experimental studies, burn injury has been shown to lead to an increase in SOR and thus induce lipid peroxidation, leading to local tissue damage, systemic complement activation and inflammation in distant organs.[18,19] Hypovolemia that develops in burn injury leads to splanchnic vasoconstriction and causes mucosal ischemia. Fluid resuscitation causes mucosal ischemia/reperfusion injury and thus excessive SOR production, leading to systemic tissue damage progression.[20,21] Increased levels of oxidative stress in lung and liver tissues as a result of burn and ischemia/reperfusion injury are thought to cause GSH to decrease due to excessive consumption.[22] In experimental studies, it has been found that allopurinol, superoxide dismutase, deferoxamine, GSH, NAS, sildenafil and other PDE inhibitors and antioxidants, such as Vit-C reduce oxidative stress and tissue damage.[23–25] In clinical studies performed in patients with septic shock, antioxidant and PDE inhibitor therapy has been shown to reduce lipid peroxidation, maintain cardiac hemodynamic stability, and reduce the number of days spent with a ventilator and in the intensive care unit.[26,27] However, antioxidant and PDE inhibitor therapy did not have any effects on mortality in these studies. This study aimed to investigate the efficacy of antioxidant and PDE inhibitor therapy in two-hit trauma models that would better mimic clinically evolving sepsis. In the literature, to our knowledge, there is no study investigating the efficacy of antioxidant and phosphodiesterase inhibitor therapy in two-hit models. PDE inhibitors are one of the agents for inhibiting the synthesis and release of cytokines.[28] Pentoxifylline, a methylxanthine derivative, inhibits TNF-α gene transcription by increasing intracellular cAMP levels.[28] Sildenafil is an increasingly common PDE-5 enzyme inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension because of its vascular dilator effect.[29,30] In addition to its vasodilation effect, sildenafil inhibits platelet aggregation and has anti-inflammatory and antioxidative properties.[31,32] Milrinone is a PDE 3 inhibitor with inotropic and vasodilatory action.[33] Milrinone shows its effect by increasing intracellular cAMP.[33] It has been emphasized in the studies that milrinone has an anti-inflammatory effect independent of its vasodilator effect.[34] Sildenafil is a specific PDE5 inhibitor.[35] It inhibits cGMP specifically and potently.[35] Sildenafil has been reported to have healing effects on inflammation and oxidative stress in the lungs and other organs. It has been proven in studies that it suppresses inflammatory events by reducing oxidative stress.[36] In their study, Yildirim et al.[37] showed a significant 522

reduction in tissue MDA level and a maintained GSH level in the group of lung fibrosis patients treated with 10 mg/kg sildenafil. In another study, sildenafil has been shown to have a renoprotective effect against oxidation and inflammation in diabetic rats.[38] In our study, the GPx level in the kidney tissue in the sildenafil group was not only higher than the control group but was significantly higher than all other groups. No significant effect of sildenafil on other parameters was observed. The MDA value was lower in the sildenafil group than in the other groups. However, this difference was not significant when compared with the control group but was significantly lower than NAS and pentoxifylline. The damage score of all tissues was significantly lower in the sildenafil group compared to the control groups. This situation suggests that sildenafil shows its protective effect on tissue damage by increasing GPx activity and decreasing lipid peroxidation. The results of our study support other studies in the literature. In the literature, different treatment doses were used in sildenafil studies. Pentoxifylline, a methylxanthine derivative, has been used for many years for its circulatory regulating effect, it has been shown to have a strong inhibitory effect on neutrophils in recent years, especially by inhibiting the release of free oxygen radicals, primarily superoxide, and lysosomal enzymes[39] and clearing hydroxyl radicals from damaged tissues.[40] PTX is also well known to reduce the TNF-α release from inflammatory cells.[41] Different results have been obtained in antioxidant studies. Sulkowska et al.[42] reported that it prevents lung injury caused by free oxygen radicals due to cyclophosphamide. PTX has been shown to have beneficial effects on sepsis in human and animal experiments.[43] PTX has been shown to improve the hemodynamic state in sepsis. [44] It prevents the passage from hyperdynamic response to hypodynamic response, improving renal blood flow.[44] Inflammatory lung injury after endotoxemia has also been shown to be improved by PTX.[45] In the study conducted by Zeni et al.,[44] it was observed that PTX decreased TNF-a and IL-1 levels in adults and newborns. In our study, the levels of SOD in the kidney tissue were significantly higher and TNF-α and catalase values were significantly lower in the PTX group. SOD levels were significantly higher in the lung tissue. The pathological damage score was found to be low only in the lung tissue. The results support previous studies in the literature. In addition, the effect of PTX on TNF-α was observed more clearly than other groups. Although the significant increase in SOD is thought to be compensatory, SOD activity may be increased by PTX. There are a limited number of studies investigating the use of milrinone in SIRS and sepsis in the literature.[46,47] Although it improves cardiac performance in these patients, it is not recommended for the treatment of sepsis because of its vasodilator effect.[48] However, the anti-inflammatory effects of milrinone, as well as cardiovascular effects, have been shown.[49,50] Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Özer et al. The effects of phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress in two-hit trauma model

Ming Gong et al.[51] to investigate the effect of milrinone on cardiopulmonary bypass associated inflammation, randomized 30 patients before cardiopulmonary bypass by inhalation of milrinone and saline. TNF-α, IL-6 and matrix metalloproteinase levels were significantly lower in the milrinone group after the operation. In our study, a significant increase in lung SOD and GPx levels, a significant decrease in TNF-α levels in kidney tissue and significant increase in GPx value were observed in the milrinone group. In addition, the damage score of all organs in the milrinone group was significantly lower than the control group. N-Acetylcysteine (NAS) is a thiol compound with potent antioxidant and anti-inflammatory properties. NAS is also a well-known glutathione (GSH) precursor.[52] NAS shows its effects by transforming into an endogenous FOR retainer, glutathione.[53,54] Phosphodiesterase (PDE) inhibitors have critical control of the intracellular signal transduction system because they hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). [31] They play a role in many pathological events, including inflammation, cancer, neurodegeneration and oxidative stress.[31]

of NAS is produced by increasing the activity of GPx and decreasing lipid peroxidation, similar to sildenafil. This can be explained by saying that the diagnostic value of the tissue levels of antioxidant enzymes and free radicals, which have a shorter life and are effective in the tissue in which they are formed, are more valuable than their serum levels. In this study, it was found that antioxidant and phosphodiesterase inhibitor treatment decreased oxidative stress level in lung and kidney tissues in a consecutive two-hit trauma model performed with CLP peritonitis after burn. Generally, the results of our study reflect the strong anti-inflammatory and antioxidant properties of PDE inhibitors. The SOD and GPx values were mostly influenced by the treatments we provided. Our results suggest that PDE inhibitors and NAS can exhibit antioxidant properties by increasing SOD and GPx enzyme activities. The role of PDE inhibitors and NAS in reducing tissue damage was evident. The antioxidant and anti-inflammatory effects of PDE inhibitors and NAS on lung tissue were found to be stronger than other organs. Milrinone was the most potent in the groups. Again, PTX and milrinone were found to be most effective on TNF-a, which played an important role in the course of sepsis.

NAS is a mucolytic commonly used in the clinic and its effects on burn injury as a precursor of GSH have been studied in the literature. For example, the use of NAS in animals with burn injury has been shown to improve cellular immunity.[55,56] Similarly, short-term 24-hour post-burn NAS treatment decreases MDA levels in lung tissue and increases GSH levels and thus decreases oxidative stress.[54] These effects of NAS are attributed to correcting cellular immunity in thermal damage.[56] NAS treatment in animals with experimental peritonitis, strengthens peritone defense mechanisms by correcting suppressed neutrophil activation.[57] On the other hand, the level of GSH increases with NAS therapy in the lung tissue, thereby reducing neutrophil infiltration.[57] It has been shown that NAS treatment acts both as a FOR retainer and also increases the level of GSH, thereby suppressing production and activity of proinflammatory cytokines and chemokines, while increasing cytotoxic T cell activity and IL-2 production.[58]

Antioxidant and phosphodiesterase inhibitor treatment is a promising treatment option for the prevention of latestage organ damage and multiple organ failure caused by the second hit, in cases where the two-hit models in MOF development, such as burn, hemorrhagic shock, and sepsis is thought to be functional. In patients who have experienced major trauma, antioxidant and phosphodiesterase inhibitor therapy may have a potential prophylactic effect in the treatment of immune deficiency, especially in the first week, before the development of the second trauma, such as an infection. Further experimental and clinical studies are needed.

These anti-inflammatory and immunostimulatory effects may explain the effects of NAS on both peritoneal defense mechanisms and the reduction of distant organ damage. In our study, a significant increase was observed in the level of GPx in the lung tissue in the group given NAS; and again in the group treated with NAS, there was a significant decrease in MDA value in the kidney tissue and a significant increase in the GPx level. In addition, the histopathological damage score of all tissues was significantly lower than the control group. Our results were similar to other studies in the literature.

Acknowledgment

The effectiveness of NAS in preventing tissue damage was observed. Our results suggest that the antioxidant effect Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

In the experimental sequential two-hit trauma model, antioxidant and phosphodiesterase inhibitor treatment suppress the level of tissue oxidative stress, and the treatment of PDE inhibitors and NAS initiated after the formation of the second trauma reduces distant organ tissue damage.

For his help in writing, Dr. To Ali Kağan Gökakın, for laboratory analysis, Dr. To Enver Sancaktar, for pathological examination, Dr. To Mehmet Tuzcu and i thank Selim Çam for statistical analysis. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Ö.Ö., M.Ş.; Design: Ö.Ö., M.Ş.; Supervision: Ö.Ö., M.Ş.; Fundings: CUBAB; Materials: Ö.Ö., M.Ş; Data: Ö.Ö., M.Ş; Analysis: Ö.Ö., M.Ş; Litera523

Özer et al. The effects of phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress in two-hit trauma model

ture search: Ö.Ö., M.Ş., U.T.; Writing: Ö.Ö., M.Ş., U.T.; Critical revision: Ö.Ö., M.Ş., U.T. Conflict of Interest: None declared. Financial Disclosure: This project was supported by Cumhuriyet University scientific research projects commission as T544.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

İki darbe modelinde spesifik ve non-spesifik fosfodiesteraz inhibitörleri ve N-asetilsisteinin oksidatif stres ve uzak organ hasarına etkisi Dr. Özdemir Özer,1 Dr. Uğur Topal,2 Dr. Metin Şen1 1 2

Cumhuriyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı,Sivas Erciyes Üniversitesi Tıp Fakültesi, Cerrahi Onkoloji Bilim Dalı, Kayseri

AMAÇ: Sepsis enfeksiyona karşı oluşan sistemik bir enflamatuvar yanıttır ve morbidite ve mortalitenin ana nedenlerinden biridir. Travma sonrası ikinci darbe artmış enflamatuvar yanıta ve çoklu organ yetersizliğine (ÇOY) neden olur. Yanık hasarı sonrası gelişen enfeksiyon iki darbe travma çalışması için uygun bir modeldir. Sepsis çoklu organ yetersizliğinde anahtar rol oynayabilecek lipid peroksidasyonuna neden olan serbest oksijen radikalleri (SOR) gibi biyokimyasal mediyatörlerin salınımına neden olur. Biz bu çalışmada iki darbe modelinde fosfodiesteraz (PDE) inhibitörleri (sildenafil, milrinon, pentoksifilin) ve N-asetilsisteinin (NAS) oksidatif stres ve organ hasarı üzerindeki etkilerini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Bu deneysel çalışmada 40 sıçanda %30’luk haşlama yanığı oluşturulduktan 72 saat sonra çekal ligasyon ve ponksiyon (CLP) yöntemi ile peritonit oluşturuldu. Sıçanlar her biri sekiz sıçandan oluşan beş gruba ayrıldı. Grup I: Tedavi uyulanmadı; Grup II: CLP sonrasında 72 saat boyunca 10/mg/kg gün dozunda intraperitoneal (i.p) sildenafil tedavisi uygulandı; Grup III: CLP sonrasında 72 saat boyunca 1/mg/kg gün dozunda i.p milrinon tedavisi uygulandı; Grup IV: CLP sonrasında 72 saat boyunca 150/mg/kg gün dozunda i.p NAS tedavisi uygulandı; Grup V: CLP sonrasında 72 saat boyunca 50/mg/kg gün dozunda i.p pentoksifilin tedavisi uygulandı. Tüm sıçanlar deneyin yedinci gününde sakrifiye edildi. Malondialdehit (MDA), glutatyon peroksidaz (GPx), süperoksit dismutaz (SOD), katalaz, tümör nekröz faktör alfa (TNF-α), düzeyleri ve histopatolojik çalışma için doku (akciğer, böbrek) ve serum örnekleri alındı. BULGULAR: Kontrol grubu ile karşılaştırıldığında tedavi edilen tüm gruplarda doku hasar skoru düşük bulundu. Sildenafil, milrinon ve NAS gruplarında böbrek GPx düzeyi kontrol grubuna göre yüksek bulundu. Akciğer dokusunda milrinon ve pentoksifilin gruplarında SOD kontrol grubuna göre yüksek bulunurken milrinon ve NAS ile GPx düzeyi yüksek bulundu. Böbrekte pentoksifilin ve milrinon gruplarında TNF-α düzeyi kontrol grubuna göre düşük bulundu. TARTIŞMA: Bu deneysel çalışma iki darbe modelinde PDE inhibitörleri ve NAS’nin oksidatif stres düzeyini ve uzak organ hasarını azaltıcı etkileri olduğunu göstermiştir. Bu konu üzerinde ileri klinik ve deneysel çalışmalara ihtiyaç vardır. Anahtar sözcükler: Antioksidan; doku hasarı; fosfodiesteraz inhibitörü; sepsis; serbest oksijen radikalleri. Ulus Travma Acil Cerrahi Derg 2020;26(4):517-525

doi: 10.14744/tjtes.2019.00570

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ORIGIN A L A R T IC L E

Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in blunt chest trauma patients İbrahim Çaltekin, M.D.,1

Şıho Hidayet, M.D.2

Department of Emergency Medicine, Yozgat Bozok University Faculty of Medicine,Yozgat-Turkey

Department of Cardiology, Malatya İnönü University Faculty of Medicine, Malatya-Turkey

ABSTRACT BACKGROUND: After blunt chest trauma, life-threatening arrhythmias may occur in the early post-injury period, as well as a few days after the injury. This study aimed to evaluate the risk of arrhythmias in blunt chest trauma patients using Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio. METHODS: In this study, patients who applied to the emergency department due to blunt chest trauma were examined prospectively. The 12-lead ECG was performed to both blunt chest trauma and control group. ECG measurements of QT and Tp-e intervals were performed from both groups. RESULTS: A total of 81 participants; 41 blunt chest trauma patients and 40 healthy volunteers were included in this study. Tpe, Tpe/ QT, Tpe/QTc values were statistically significant in the trauma group compared to the control group (p<0.001). Although Tpe/QTc, max QT and min QT were statistically significant (p<0.05) in patients with a rib fracture, no difference was detected concerning Tpe, Tpe/QT compared to no-rib fracture group (p>0.05). CONCLUSION: Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in ECG predict the arrhythmias that may occur in blunt cardiac trauma, especially in blunt chest trauma patients. Keywords: Arrhythmia; blunt chest trauma; emergency department.

INTRODUCTION Blunt chest trauma develops after severe trauma to the chest wall and may cause injury to crucial structures, such as the lung, diaphragm, heart, pleura or pericardium.[1] Blunt chest trauma has an approximately 15% rate among all emergency trauma cases, and a considerable part of this type of trauma results in mortality.[2] Also, many complications may occur after blunt chest trauma.[3] The development of rare cardiac arrhythmias is an indirect indicator of the presence of cardiac involvement.[4,5] In addition to this, when an arrhythmia due to blunt chest trauma is detected, all types of arrhythmias, such as supraventricular tachycardia, atrial fibrillation, ventricular tachycardia and ventricular fibrillation, have been reported to develop from the atrium and ventricle of the heart.[6]

The QT interval (QT), corrected QT interval (QTc), QT dispersion and transmural dispersion of repolarization (TDR) are accepted as determinants of myocardial repolarization.[7] Tp-e, the interval between peak and end of T wave on electrocardiogram (ECG), is known to be a predictor of ventricular repolarization with transmural dispersion.[8] The Tp-e/QT ratio and the Tp-e/QTc ratio are also used as determinants for the development of ventricular arrhythmia on electrocardiography and it is thought to be the most important determinant of the increased mortality risk. The Tp-e/QT ratio and the Tp-e/QTc ratio are also known as electrocardiographic markers for the development of ventricular arrhythmia.[8–10] After blunt chest trauma, life-threatening arrhythmias may occur in the early post-injury period, as well as a few days

Cite this article as: Çaltekin İ, Hidayet Ş. Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in blunt chest trauma patients. Ulus Travma Acil Cerrahi Derg 2020;26:526-530. Address for correspondence: İbrahim Çaltekin, M.D. Yozgat Bozok Üniversitesi Tıp Fakültesi, Acil Tıp Kliniği, Yozgat, Turkey Tel: +90 354 - 212 44 42 E-mail: drcaltekin@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):526-530 DOI: 10.14744/tjtes.2020.45642 Submitted: 25.10.2019 Accepted: 23.03.2020 Online: 16.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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after the injury.[6] In literature, there are not enough data to evaluate Tp-e interval, Tp-e/QT ratio and Tp-e /QTc ratio as markers of cardiac arrhythmogenesis in patients with blunt chest trauma. In this study, we aimed to evaluate the risk of arrhythmias in blunt chest trauma patients using Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio.

MATERIALS AND METHODS Study Design In this study, patients who applied to the emergency department due to blunt chest trauma within six months were examined prospectively. This study included a total of 81 participants, 41 patients with blunt chest trauma, and 40 healthy volunteer as a control group. The control group participants were randomly selected from patients over 18 years old who applied to the emergency department. This study was carried out in the Bozok University Faculty of Medicine, Department of Emergency Medicine after the approval of our institution’s local ethics committee (2018-KAEK-189_2018.01.25_25) and informed consent was obtained from each participant.

The 12-lead ECG was performed to both blunt chest trauma and control group. Nihon Kohden ECG 1250 Cardiofax S (2009, Tokyo, Japan) was used at a paper speed of 50 mm/s. ECG was performed while the participants at rest in the supine position while the heart was in a resting period. Measurements of QT and Tp-e intervals were performed manually. Patients with U wave on ECG data were excluded from this study. The average of three data obtained from the ECG of each lead was used. The QT interval is the area from the beginning of the QRS wave to the end of the T wave[11] and was evaluated according to the corrected heart rate using the Bazett formula: QTc = QTd/√ (RR). The QTd was defined as the calculation of the difference between the maximum (QTmax) and the minimum QT (QTmin). Calculation of the difference between corrected QTmax (cQTmax) and corrected QTmin (cQTmin) detected the corrected QTd (cQTd).[12] All data were collected by an emergency medical physician, QT and Tp-e interval measurements were performed by two cardiologists who were blinded to clinical and symptoms of the patients.

Statistical Analysis

Study Population Medical history, weight and height measurements of the participants were taken and body mass index (BMI) was calculated as weight/height2 ratio (kg/m2). ECG records, heart rate, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), age values and findings were evaluated in both patient and control groups. Patients with a history of cardiac arrhythmia, hypertension, atrial fibrillation, coronary artery disease, chronic kidney and liver disease, coronary artery disease, diabetes mellitus, hyperthyroidism or hypothyroidism history which may cause arrhythmia, and patients with electrolyte abnormalities, moderate and severe heart valve disease, history of arrhythmia, heart failure, permanent pacemaker, any cardiac branch block, any other signs of intraventricular conduction defect, antiarrhythmic (digoxin, B-Blocker, Ca antagonist) drug usage, smoking history and patients who had tachycardia (>100 beats/minute) or bradycardia (<60 beats/minute) on ECG recordings were excluded from this study. (a)

Electrocardiography

Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) version 20.0 software. The obtained data were expressed as mean±standard deviation. Visual (histograms, probability graphs) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk test) were used to determine whether the variables distributed normally. An independent sample t-test was used to compare variables with normal distribution, and the Mann-Whitney U test was used to compare variables without normal distribution. Chi-square test or Fischer’s exact test (when the chisquare test assumptions are not made due to low expected cell counts) were used to compare rates in different groups when it was available. P<0.05 was considered statistically significant.

RESULTS A total of 81 participants, 41 blunt chest trauma patients and 40 healthy volunteers were included in this study.

(b)

90.0

(c)

.22

Tpe

80.0 75.0 70.0 65.0

.20

Tpe/QTc.ratio

Tpe/QT ratio

85.0

.22

.18 .16

.18 .16 .14 .12

60.0 Blunt chest trauma group

Control group

Blunt chest trauma group

Control group

Blunt chest trauma group

Control group

Figure 1. Comparison of the Tp-e interval (a), Tp-e/QT ratio (b) and Tp-e/QTc ratio (c) between the blunt chest trauma and control groups.

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Clinical data and variables of patients with blunt chest trauma and control group are shown in Table 1. In the trauma group, there were 30 male and 11 female patients; and the control group consisted of 30 male and 10 female. Age distribution of the groups was as follows: 41.37±16.15 in blunt chest trauma group and 37.78±14.62 in the control group. Age, BMI, SBP, DBP, HR, RR parameters were not found to be statistically significant in trauma cases compared to the control group (p>0.05). Tpe (trauma 80.71±3.55, control 65.83±2.69, p<0.001), Tpe/ QT (Trauma 0.21±0.01, control 0.17±0.01, p<0.001) Tpe/ QTc (Trauma 0.19±0.01, control 0.15±0.01, p<0.001) values were statistically significant in the trauma group compared to the control group. cTpe (trauma 89.17±6.31, control 71.52±4.73, p<0.001), maxQT (trauma 400.30±12.79, control 410.83±10.86, p<0.001), minQT (Trauma 373.69±10.24, contol 385.18±10.35, p<0.001), QT (Trauma 387.10±11.29, control 398.00±10.35, p<0.001) were also found to be statistically significant. QT dispersion and QTc dispersion values were not found to be statistically significant (p>0.05) in trauma cases compared to the control group.

The etiology of blunt chest trauma cases is shown in Table 2. When the etiology of blunt chest trauma was examined, it was found that 20 patients had fallen from heights, six patients had motor vehicle accidents, three patients had pedestrian injuries, five patients had blunt forced trauma, and seven patients had other reasons. Evaluation of trauma severity and ECG parameters are shown in Table 3. Patients with blunt chest trauma were divided into two groups, with six patients with a rib fracture, and 35 patients with no-rib fracture. In statistical analysis results, although Tpe/QTc, max QT and min QT were statistically significant (p<0.05) in patients with a rib fracture, no difference was detected concerning Tpe, Tpe/QT compared to no-rib fracture group (p>0.05). Table 2. The etiology of blunt chest trauma cases Patient groups

Etiology

Blunt chest trauma

Fall from height

Motor vehicle accident

Pedestrian injury

Blunt forced trauma

Table 1. Statistical analysis of the data and variables

Other reasons

Variables

Totally 41

Age (years) BMI (kg/m2)

Trauma Control p (n=41) (n=40) 41.37±16.15

37.78±14.62

0.335

Totally

26.46±4.19 26.35±3.07 0.757

SBP (mmHg)

130.00±11.46

127.13±12.96

0.262

DBP (mmHg)

75.98±8.38

75.63±8.78

0.926

HR (bpm)

73.46±8.07

70.98±7.10

0.145

RR (ms)

0.83±0.09

0.85±0.08

0.167

Tpe (ms)

80.71±3.55

65.83±2.69

<0.001

cTpe (ms)

89.17±6.31

71.52±4.73

<0.001

maxQT (ms)

400.30±12.79

410.83±10.86 <0.001

minQT (ms)

373.69±10.24

385.18±10.35 <0.001

QT (ms)

387.10±11.29

398.00±10.35 <0.001

QTc (ms)

429.20±28.11

431.70±23.73

0.666

maxQTc (ms)

443.58±28.92

445.40±24.99

0.764

minQTc (ms)

414.02±25.67

417.50±23.22

0.525

QTdispersion (ms)

26.85±5.67

25.65±4.73

0.258

QTc dispersion (ms)

29.80±7.10

27.90±5.33

0.177

Tpe/QT

0.21±0.01 0.17±0.01 <0.001

Tpe/QTc

0.19±0.01 0.15±0.01 <0.001

Variable are presented as mean±standard deviation. BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HR: Heart rate; Tp-e: Transmural dispersion of repolarization; cTpe: Corrected transmural dispersion of repolarization; QTmax: QTmaximum; QTcmax: Corrected QT maximum; QTmin: QT minimum; QTcmin: Corrected QT minimum; QTd: QT dispersion; QTcd: Corrected QT dispersion; Tp–e/QT: Transmural dispersion of repolarization; Tp–e/QTc: Transmural dispersion of repolarization/corrected QT.

528

Control Totally

Table 3. Evaluation of the trauma severity and electrocardiogram parameters Variables

Rib fracture No fracture (n=6) (n=35)

Tpe (ms) maxQT (ms)

83.68±2.88

80.20±3.44

0.220

410.67±10.80

398.51±12.37

0.030

minQT (ms)

381.17±9.68

372.40±9.90

0.037

QT (ms)

396.17±10.30

385.54±10.83

0.031

425.94±27.07

0.073

QTc (ms)

448.17±28.89

maxQTc(ms)

464.67±32.16 439.97±27.21 0.052

minQTc (ms)

431.50±30.85

411.03±23.92

0.071

QTdispersion (ms)

29.50±2.43

26.40±5.96

0.481

QTcdispersion (ms)

33.17±2.56

29.23±7.48

0.230

Tpe/QT

0.21±0.01 0.21±0.01 0.984

Tpe/QTc

0.19±0.01 0.19±0.01 0.028

cTpe (ms)

94.63±6.16

88.24±5.921

0.020

Variable are presented as mean±standard deviation. Tp–e: Transmural dispersion of repolarization; cTpe: Corrected transmural dispersion of repolarization; QTmax: QTmaximum; QTcmax: Corrected QT maximum; QTmin: QT minimum; QTcmin: Corrected QT minimum; QTd: QT dispersion; QTcd: Corrected QT dispersion; Tp–e/QT: Transmural dispersion of repolarization; Tp–e/QTc: Transmural dispersion of repolarization/corrected QT.

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DISCUSSION Cardiac injury due to blunt chest trauma and cardiac arrhythmia, as a result, is related to the violence of the impact on the chest wall, where it is applied, and which stage of the cycle during heart beat occurred.[13] When the study data is examined, it is possible to provide early diagnosis of arrhythmias caused by blunt chest trauma and indirect blunt cardiac trauma by determining Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratios. Several mechanisms have been proposed to identify traumatic cardiac arrhythmias, such as ischemia and hypoxia, perfusion disorders, increased vagal sympathetic stimulation, and excessive conduction of damaged myocardial cells. Ismailov et al.[6] showed that blunt chest trauma and blunt heart injury might be the cause of many kinds of arrhythmias, especially atrial fibrillation. Increased Tp-e interval has been found to be a risk predictor for the development of malignant arrhythmias. These arrhythmias have not been affected by the presence or absence of structural heart disease in the patient.[14] The time interval between the T wave and the end of the T wave is generally expected to indicate the difference in repolarization time between subendocardial and subepicardial myocardial cells, and this interval leads to the evaluation of the transmural dispersion of the precordial repolarization as a marker of ECG. [15,16] Recently, the elongated interval of Tp-e appears to be a valuable sign for predicting ventricular arrhythmia and cardiovascular disorders. Tp-e interval and Tp-e/QT ratio have been reported to be associated with increased ventricular repolarization distribution. Elongation of the Tp-e interval has been reported to be related to ventricular arrhythmia and sudden cardiac death. These values are also expressed as new electrocardiographic markers.[17] The Tp-e/QT ratio measured from precordial leads is 0.21 ms in healthy adults with normal heart rate (60–100 beats/min).[18] In this study, Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio values in ECG were determined and predictability of ventricular arrhythmogenesis via ECG was evaluated. Cardiac arrhythmia as a result of blunt chest trauma is a rare condition.[19] Although it seems rare, various arrhythmias, such as atrial flutter and fibrillation, extrasystoles and ventricular tachycardia, may develop secondary to blunt chest trauma.[6,18–20] Kilicaslan et al.[7] reported that Tp-e/QT, Tp-e/ QTc values increased in Obstructive Sleep Apnea Syndrome, and it was possible to determine the possibility of arrhythmia development in patients with Obstructive Sleep Apnea Syndrome by looking at these markers. In many studies with a similar perspective, it has been reported that Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio can predict the development of arrhythmia in many diseases, such as diabetes mellitus, ankylosing spondylitis, hypothyroidism, hypertrophic carUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

diomyopathy.[7–9,21,22] In our study, the Tp-e interval, which is one of the arrhythmia markers, was found to be higher in the patient group than the control group, and Tp-e/QT, Tp-e/QTc values were statistically significant in the trauma group compared to control group. However, when the cases of blunt chest trauma were divided into subgroups, it was found that the presence of rib fracture did not affect all the markers of arrhythmia, even if it showed statistically significant results in some markers.

Limitations Although there are some limitations in our study, the most important limitation is the limited number of patients. In addition, the obligation of evaluation only in selected trauma cases is another limitation. Although arrhythmia development has been reported in patients with blunt chest trauma, even in pos-traumatic follow-up, in our study, long-term clinical follow-ups and rhythm holter follow-up could not be performed. Long-term rhythm Holter monitoring and large patient groups are needed to emphasize the importance of Tp-e interval, Tp-e/QT and Tp-e/QTc ratios in predicting the risk of cardiac dysrhythmia in patients with blunt chest trauma.

Conclusion Although there are many studies about arrhythmia development in patients with blunt chest trauma, to our knowledge, the Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio of blunt chest trauma cases were not investigated in any study. In conclusion, Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in ECG predict the arrhythmias that may occur in blunt cardiac trauma, especially in blunt chest trauma patients. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: İ.Ç., Ş.H.; Design: İ.Ç., Ş.H.; Supervision: Ş.H.; Fundings: İ.Ç., Ş.H.; Materials: İ.Ç., Ş.H.; Data: İ.Ç.; Analysis: İ.Ç., Ş.H.; Literature search: İ.Ç., Ş.H.; Writing: İ.Ç.; Critical revision: Ş.H. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Künt göğüs travması hastalarında Tp-e aralığı, Tp-e/QT oranı ve Tp-e/QTc oranının değerlendirilmesi Dr. İbrahim Çaltekin,1 Dr. Şıho Hidayet2 1 2

Yozgat Bozok Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Yozgat Malatya İnönü Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı,Malatya

AMAÇ: Künt göğüs travmasından sonra, yaralanma sonrası erken dönemde ve yaralanmadan birkaç gün sonra hayati tehlike oluşturan aritmiler ortaya çıkabilir. Bu çalışmada, künt göğüs travma hastalarında Tp-e aralığı, Tp-e/QT oranı ve Tp-e/QTc oranı kullanılarak aritmi riskini değerlendirmeyi amaçladık. GEREÇ VE YÖNTEM: Bu çalışmada künt göğüs travması nedeniyle acil servise başvuran hastalar ileriye yönelik olarak incelendi. Künt göğüs travması ve kontrol gruplarına 12 derivasyonlu EKG uygulandı. Her iki gruptan da QT ve Tp-e aralıklarının EKG ölçümleri yapıldı. BULGULAR: Kırk bir künt göğüs travmalı hasta ve 40 sağlıklı gönüllü olmak üzere, toplamda 81 katılımcı çalışmaya dahil edildi. Tpe, Tpe/QT, Tpe/ QTc değerleri travma grubunda kontrol grubuna göre istatistiksel olarak anlamlıydı (p<0.01). Her ne kadar Tpe/QTc, maksimum QT ve min QT, kaburga kırığı olan hastalarda istatistiksel olarak anlamlı olsada (p<0.05) kaburga kırığı olmayan gruba göre Tpe, Tpe/QT açısından fark bulunmadı (p>0.05). TARTIŞMA: EKG’de Tpe aralığı, Tp-e/QT oranı ve Tp-e/QTc oranı, künt kardiyak travmada, özellikle künt göğüs travma hastalarında oluşabilecek aritmileri öngörmektedir. Anahtar sözcükler: Acil servis; aritmi; künt göğüs travması. Ulus Travma Acil Cerrahi Derg 2020;26(4):526-530

530

doi: 10.14744/tjtes.2020.45642

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ORIGIN A L A R T IC L E

The effects of analgesic treatment and chest physiotherapy on the complications of the patients with rib fractures that arise from blunt chest trauma Timuçin Alar, M.D.,1

İsmail Ertuğrul Gedik, M.D.,2

Murat Kara, M.D.3

Department of Thoracic Surgery, Çanakkale Onsekiz Mart University Faculty of Medicine, Çanakkale-Turkey

Department of Thoracic Surgery, Erzurum Regional Education and Research Hospital, Erzurum, Turkey

Department of Thoracic Surgery, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: This prospective study aims to investigate the effect of chest physiotherapy and analgesic therapy on the possible complications of isolated rib fractures attributable to blunt thoracic trauma, such as hemothorax and pneumothorax. METHODS: Patients who presented to Çanakkale Onsekiz Mart University School of Medicine Hospital’s Emergency Department and Thoracic Surgery outpatient clinics within the first 24 hours of the post-traumatic period and did not have additional intrathoracic complications at presentation with blunt thoracic trauma and who were diagnosed with isolated rib fractures were enrolled in this prospective research study. The groups were designated as the patients who would receive analgesic treatment only (Group A) and the patients who would receive chest physiotherapy and analgesic treatment together (Group B). Patients who had first and second rib fractures or three or more rib fractures and who did not have additional organ injury were hospitalized in the Thoracic Surgery clinics; patients who had other organ trauma were hospitalized in related clinics. Patients were reassessed on their seventh and 30th post-traumatic days with physical examination and radiologic studies. RESULTS: The mean age of the 114 patients were 56.3±16.4 (22–87). There were 37 (32.5%) women and 77 (67.5%) men. Each group included 57 patients. The most common form of trauma was the same-level falls (31.6%). The mean number of rib fractures of all participants was 2.6±0.7 (1–10); the median number was 1.5. Fifty-two (45.6%) patients were hospitalized. The mean length of stay was 4.0±1.1 days. At the end of their treatment and follow-up periods, pleural effusion was found in 28 patients (24.6%) out of 114 enrolled at the side of trauma. Group B had a higher number of patients with pleural effusion (43.9%) than group A (5.3%). We performed tube thoracostomy in four patients, all of which were in group B (p<0.05). CONCLUSION: As a result of this study, chest physiotherapy maneuvers have increased the incidence of late hemothorax in patients with three or more isolated rib fractures. Also, minimal hemothoraces (<300 ml) may spontaneously regress, and no additional surgical treatment are required if the proper follow-up procedures are performed. It is advisable to hospitalize the blunt thoracic trauma patients who have three or more rib fractures and who are planned to undergo chest physiotherapy and or are prone to develop additional complications because of possible risks. Keywords: Blunt thoracic trauma; chest physiotherapy; hemothorax; rib fracture.

INTRODUCTION Traumas are generally divided into two groups as blunt and penetrating traumas. Blunt traumas have higher morbidity

and mortality rates because of additional organ and system injuries that accompany them.[1]

Cite this article as: Alar T, Gedik İE, Kara M. The Effects of analgesic treatment and chest physiotherapy on the complications of the patients with rib fractures that arise from blunt chest trauma. Ulus Travma Acil Cerrahi Derg 2020;26:531-537. Address for correspondence: Timuçin Alar, M.D. Çanakkale Onsekiz Mart Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, Çanakkale, Turkey Tel: +90 286 - 263 59 50 E-mail: timucinalar@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):531-537 DOI: 10.14744/tjtes.2019.26356 Submitted: 24.02.2019 Accepted: 09.12.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Alar et al. The effects of AT and CP on the complications of the patients with RF that arise from blunt chest trauma

Rib fractures (RF) are the most common complication trauma patients as they occur in 10% of the trauma patients. RF may cause pulmonary contusion hemopneumothorax and pulmonary laceration.[1] Additionally, RF may hinder the respiration mechanism and cause secretion retention in the airways and thus cause serious complications, such as atelectasis and pneumonia attributable to the pain they cause.[2] Unfortunately, there is not enough scientific information about chest physiotherapy (CP), which is performed to prevent such complications that may or may not cause hemopneumothorax. The effects of CP and analgesic treatment (AT) on the development of hemopneumothorax in patients with isolated rib fractures secondary to blunt thoracic trauma (TT) is researched in this prospective randomized study.

MATERIALS AND METHODS This prospective research study was approved by the Human Studies Ethical Committee of Çanakkale Onsekiz Mart University (Date: 13/02/2013 Decision Number: 2013/05-04). Patients who were diagnosed with isolated RF secondary to blunt TT who presented to Çanakkale Onsekiz Mart University School of Medicine Hospital’s Emergency Department and Thoracic Surgery outpatient clinics in the first 24 hours following the trauma between 03/01/2013-03/01/2016 were enrolled. The diagnosis of RF was established with patients’ medical history, physical examination (PE), posterior-anterior (PA) chest x-ray, and thoracic computerized tomography (CT). The informed consent of all patients was obtained who participated in this study. Patients who had additional intrathoracic injuries, such as hemothorax, pneumothorax, flail chest, atelectasis, pneumonia or requiring hospitalization to intensive care unit (ICU) at the time of hospital admission, were excluded from this study. Patients who had predisposing medical conditions for pneumothorax, such as bullous emphysema and predisposing medical treatment with antiaggregant or anti-coagulant drugs at the time of admission, were not enrolled. However, patients with additional extrathoracic organ injuries were enrolled. Patients were divided into two groups using a shuffled deck of cards within a closed envelope. The groups were designated as the patients who will receive AT only (Group A) and the patients who will receive CP and AT together (Group B). Patients who were diagnosed with first and second RF and patients with three or more RF were hospitalized in the Thoracic Surgery Clinics. Patients who had additional extra-thoracic organ injuries were hospitalized in the respective clinics. The necessary treatments were arranged in the outpatient clinics to the patients who did not meet these criteria. All cases were evaluated twice in the Thoracic Surgery outpatient clinics at the end of the first week and the first month following their trauma with PE and radiological studies. A similar follow-up protocol was performed to the patients who were still hospitalized at the end of the first week after their trauma. The consort diagram of the study is given in Figure 1. 532

Analgesic Treatment Diclofenac sodium (2x75 mg/day intramuscular), acetaminophen (2x1000 mg/day intravenous or 4x500 mg peroral) and thiocolchicoside (2x4 mg/day intramuscular) were administered to the patients who were hospitalized at the Thoracic Surgery or other clinics with the diagnosis of isolated rib fractures for seven days. Patients did not receive additional treatment during this period. Patients who were hospitalized were evaluated with daily PE and hemogram tests. PA chest x-rays were performed to the patients with diminished lung auscultation sounds and decreased hemoglobin levels. A decrease of 1gr/dl in hemoglobin is considered significant only if confirmed with the PE. Thoracic ultrasonography (USG) was performed to all patients with findings suggesting pleural effusion on PA x-rays. The presence and the amount of pleural effusions were determined with USG. We performed diagnostic thoracentesis to all patients who had pleural effusions on USG to investigate if the pleural effusion is of hemorrhagic origin. Patients who had pleural effusions with the volume higher than what was necessary enough to diminish the costo-phrenic sinus on PA x-ray (approximately 300 ml) underwent chest tube thoracostomy using a 32 French (Fr) chest tube. Cases with lesser amounts of pleural effusions were evaluated with daily PE, hemogram tests and PA x-rays. Chest tubes were removed from the patients when the daily drainage levels were below 200 ml. Patients who were followed up on outpatient clinics were prescribed with diclofenac sodium (2x75 mg/day per-oral), acetaminophen (4x500 mg per-oral) and thiocolchicoside (2x4 mg/day per-oral) for seven days. Acetaminophen (4x500 mg per-oral) was prescribed for an additional seven days to the patients who still describe pain after this period. The patients who were hospitalized were prescribed the same drugs on their discharge. Patients were evaluated for the presence of complications at the outpatient clinical examinations with PE and PA chest x-ray at the end of their treatment. Identical procedures were performed to the patients who develop signs of pleural effusion.

Chest Physiotherapy Patients who were in the chest physiotherapy group performed incentive spirometry in addition to the identical analgesic treatment with the other group. Incentive spirometry was performed with intentional coughs five times every hour and inspiration/expiration exercises five times every 30 minutes using the Triflow device. In addition to those maneuvers, patients were mobilized for 15 minutes every three hours when they were awake. Postural drainage and chest percussion maneuvers were not performed. Patients who were treated at outpatient clinics were taught how to perform these maneuvers thoroughly and were asked to perform them during their first outpatient clinics examinations. Patients were also given checklists and asked to bring Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Alar et al. The effects of AT and CP on the complications of the patients with RF that arise from blunt chest trauma

Enrollment

Assessed for eligibility (n=198)

Excluded (n=75) - Not meeting inclusion criteria (n=63) - Declined to participate (n=12)

Randomized (n=123)

Allocation

Allocated to intervention (n=63)

Allocated to intervention (n=60)

- Received allocated intervention (n=63)

- Received allocated intervention (n=60)

- Did not receive allocated intervention (n=0)

Follow-up - Lost to follow-up (did not admit for

- Lost to follow-up (did not admit for

outpatient follow-up, did not admit

outpatient follow-up, did not admit for

for outpatient follow-up on the

outpatient follow-up on the

appointment date) (n=6)

appointment date) (n=3) Analysis

Analyzed (n=57)

- Excluded from analysis (n=0)

Figure 1. The consort diagram of this study.

them to their follow-up examinations to be certain that they performed chest physiotherapy maneuvers.

Statistical Analysis G*Power (v3.1.9) software was used for power analysis to determine the sample size. A pilot research study was performed, including 20 patients in each group. Late-onset hemothorax ratio was found in one (5%) patient in Group A and five (25%) patients in Group B. The sample size was calculated using these results of the pilot study. According to the results of the pilot study, the effect size was found to be w: 0.280 on the α=0.05 and β=0.20 levels. The required sample size for this study was found to be 101 cases, and considering the data losses, this number was increased by 20%. Thus, the final calculation was found as 121. Distribution and frequency of the data were analyzed after the data was transferred to digital media. Treatment and control groups were compared with each other for the demographic data. Descriptive values, such as mean, median, standard deviation, range, and percentage, were calculated. The difference between the means of numerical values was calculated using the Mann-Whitney U test. Categorical data differences Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

between the two groups were analyzed using the Pearson Chi-Square test. Fisher’s exact test was used if a value in the Chi-Square test was less than 5. The explanatory power of the study model for the hypothesis was evaluated using Cox & Snell R Square and Nagelkerke R Square Binominal Logistical Regression Analysis. The p-value of less than 0.05 was considered to be statistically significant in all statistical tests. All statistical analysis was carried out using the Statistical Package for Social Sciences (SPSS®) version 19 software.

RESULTS The mean age of the 114 participants were 56.3±16.4 (22-87) And 37 patients (32.5%) were women and 77 (67.5%) were men. The mean age of the women was 56.2±14.9 (28–86), and the mean age of the men was 56.3±17.1 (22–87). The comparison of the mean ages of both groups was not statistically significant (p>0.05). Group A (Analgesic) B (Analgesic and Chest Physiotherapy) included 57 patients each. The mean age of Group A was 54.2±16.1 (22–86), Group B was 58.4±16.5 (22–87), and the difference between the two groups was not statistically sig533

Alar et al. The effects of AT and CP on the complications of the patients with RF that arise from blunt chest trauma

nificant (p>0.05). Group A included 20 (35.1%) women and 37 (64.9%) men. Group B included 17 (29.8%) women and 40 (70.2%) men. The difference between the two groups was not statistically significant (p>0.05). Patients’ trauma types were grouped as motor vehicle accidents, in which the victim was a car occupant (MVA), motor vehicle accidents in which the victim was a pedestrian (MVAP), motorbike accident (MA), fall from heights (FFH) and fall from the same level (FFS). The most common type of accident in our study was FFS. The types of trauma were compared between the two groups, and there was no statistically significant difference between them (p>0.05). The distribution of trauma types among the groups is detailed in Table 1. The mean number of RF of 114 patients enrolled in our study was 2.6±0.7 (1–10); the median number was 1.5. The mean number of RF in both groups was calculated to be 2.2±1.5 (1–7) for Group A and 3.0±2.0 (1–10) for group B. The median number of RF was two for Group A and three for Group B. The difference between the mean RF between the two groups was statistically significant (p<0.018).

of 114.7 (12.9%) patients were in Group A, and 11 (19.3%) of the patients were in Group B. Regarding extra-thoracic injuries there was no statistically significant difference between two groups (p>0.05). The most common type of extra-thoracic injury was the fracture of the transverse processes of the thoracic vertebrae. At the end of the treatment and follow-up periods, there were 28 (24.6%) out of 114 patients who were diagnosed with pleural effusion at the same side of RF. We performed thoracentesis to these 28 patients to establish the diagnosis of hemothorax. All of these 28 pleural effusions were hemothoraces. The distribution of patients who developed hemothorax between two groups was calculated, and Group B was found to have significantly (p<0.0001) more patients with hemothorax than Group A (Table 3). Table 2. The distribution of the patients who were hospitalized and who were treated in outpatient clinics between two groups Treatment status

In this study, 52 (45.6%) out of 114 patients were hospitalized. The distribution of the patients who were hospitalized and who were treated in outpatient clinics between the two groups is detailed in Table 1. The difference of the patients who were hospitalized and who were not hospitalized between the two groups was not statistically significant (p>0.05) (Table 2). The mean hospital stay of the patients who were enrolled in our study was 4.0±1.1 days. The mean hospital stay of the patients in Group A was 3.6±0.8 days and 4.3±1.2 days in Group B. The mean hospital stay of the patients in Group B was significantly longer than Group A (p<0.003). There were extra-thoracic injury in 18 (15.8%) patients out Table 1. The distribution of the trauma types among the groups Trauma type

Total

n (%)*

3 (5.3)

5 (8.8)

8 (7.0)

pedestrian

12 (21.1)

14 (24.6)

26 (22.8)

Fall from same level

22 (38.5)

14 (24.6)

36 (31.6)

Fall from heights

14 (24.6)

19 (33.2)

33 (28.9)

Motor vehicle accidents,

Motorbike accidents

6 (10.5)

5 (8.8)

11 (9.7)

Total

57 (100)

114 (100)

*Column percentages were calculated.

534

Total

n (%)*

Outpatient clinics

34 (59.6)

28 (49.1)

62 (54.4)

Hospitalized

23 (40.4)

29 (50.9)

52 (45.6)

Total

57 (100)

114 (100)

*Column percentages were calculated.

Table 3. The distribution of the patients who developed hemothorax between two groups Result of follow-up

n (%) *

No hemothorax Hemothorax Total

Total

n (%) *

n (%)*

54 (94.7)

32 (56.1)

86 (75.4)

3 (5.3)

25 (43.9)

28 (24.6)

57 (100)

114 (100)

*Column percentages were calculated.

Table 4. The distribution of the patients who were treated in outpatient clinics between two groups

Motor vehicle accidents, car occupant

Patients treated in outpatient clinics No hemothorax Hemothorax Total

Total

n (%)*

34 (100)

27 (96.4)

61 (98.4)

0 (0)

1 (3.6)

1 (1.6)

34 (100)

28 (100)

62 (100)

*Column percentages were calculated.

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Only one (1.6%) patient out of 62 patients who were treated in outpatient clinics developed hemothorax who was also in group B (Table 4). The patient recovered spontaneously without any intervention. Chest tube thoracostomy was carried out in four (14.3%) out of 28 patients who developed hemothorax. All patients who underwent tube thoracostomy were in Group B. When the difference concerning surgical intervention was compared between two groups, having all four tube thoracostomies were performed in Group B was statistically significant (p<0.041). The 24 patients’ whose tube thoracostomy was not performed had hemothorax just enough to consolidate the costo-phrenic sinus (<300 ml). Changes in the hemothorax amount were inspected using PE, PA x-rays, or thoracic USG daily during the hospital stay and at the 7th and 30th days after discharge. Hemothoraces of all these patients regressed spontaneously, and no additional surgical intervention was required at the end of the 30 days follow-up. The patients enrolled in our study were regrouped as the patients who had three or more RF and the ones with less than three. There were 67 (58.8%) patients with less than three RF, and 47 (41.2%) had more than three RF. When we compared our original groups regarding the number of RF, Group A had 34 patients with RF less than three and 23 patients with three or more. Group B had 28 patients with less than three RF and 29 with three or more RF. There was no statistically significant difference between the two groups (p>0.05). Two groups were compared for the development of complications. No patients developed hemothorax in patients with less than three RF. In contrast, all patients who developed hemothorax had three or more RF. The mean hospital stay of the four patients who undergone chest tube thoracostomy out of 52 who were hospitalized was 6.5±1.3 days, and 48 patients who did not require surgical intervention were 3.8±0.8 days. The difference between the mean duration of hospital stay was statistically significant (p<0.0001). None of the 114 patients developed complications, such as pneumothorax, atelectasis, or pneumonia, retained hemothorax, empyema, and there was no mortality. The power of our study to explain the hypothesis was analyzed with binominal logistical regression analysis. The results of this analysis were 54.3% in Cox & Snell R Square and 80.9% in Nagelkerke R Square.

DISCUSSION Trauma is still an important etiology of morbidity and mortality. It has been reported as the most common cause of death between ages 1–44. Blunt TT is the direct cause of death in 25% of the trauma patients and is an additional etiological factor in another 50% of deaths that arises from trauma. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Thus, TT is present in 75% of the patients who succumbed to trauma.[3] The most common cause of all TT and blunt TT is MVA. A study from Turkey identified that MVA is the cause of TT in 63%, and falls are the cause of 25%.[4] In international studies, MVA constitutes 43.7%–45%, and falls constitute 20% of the TT, which are less than Turkey’s data.[5,6] In our study, the most common cause of blunt TT has been found to be falls passing MVA. We believe that this situation is caused attributable to the presence of agricultural and livestock farming facilities in our hospital’s region. The mean age of the 114 participants in our study were 56.3±16.4 (22–87). This is higher compared to similar studies about blunt thoracic trauma.[7] We believe this result occurred because the hospital that this study was conducted is in the city of Çanakkale, which has the second oldest median age (36.7) in Turkey.[8] In our study, 18 (15.8%) cases had extra-thoracic injuries. The most common type of extra-thoracic injury was the fracture of the transverse processes of thoracic vertebrae, which is compatible with other studies.[5] None of our patients developed complications, such as pneumothorax, atelectasis, or pneumonia, retained hemothorax, empyema, and there was no mortality. The incidence of atelectasis in blunt TT is reported between 1.7%–10.2%.[7,9] We think that the reason our patients did not develop atelectasis is proper pain management, and the patients who were enrolled have isolated RF. It was reported that 25% of patients who had multiple RF develop pneumothorax, and 81% of the patients who had two or more RF develop hemothorax.[10] Traumatic hemo-pneumothoraces usually occur in the acute post-traumatic period, but they may also occur in a chronic setting.[10] Hemothorax is reported to develop more often than pneumothorax in chronic post-traumatic period.[11,12] When the patients enrolled in our study were regrouped as the patients who had three or more RF and the patients with less than three RF, delayed hemothorax developed only in the former group. At the end of the treatment and follow-up periods, there were 28 (24.6%) out of 114 patients who were diagnosed with hemothorax at the same side of RF. Three of the 28 patients were in Group A and 25 patients were in Group B. The incidence of delayed hemothorax in Group A in which the patients received analgesic treatment only was 5.3%, but it was 43.5% in Group B in which patients received both analgesic treatment and chest physiotherapy together. In contrast to similar studies in which the incidence of delayed hemothorax is around 5%, this 43.5% ratio is exceptionally high.[12] We believe that the difference in the incidence of delayed hemothorax arises from chest physiotherapy performed in Group B. It is suggested that all traumatic hemothoraces should be 535

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drained with chest tube thoracostomy regardless of their volume,[13] but several studies suggest that hemothoraces with the volume less than 300 ml can be observed without performing chest tube thoracostomy if the patient’s general status is good.[14] The patients who developed hemothorax but did not undergo chest tube thoracostomy had pleural effusion just enough to consolidate the costo-phrenic sinus (<300 ml). The hemothoraces in all these patients spontaneously regressed without the need for surgical intervention. The hemothoraces less than 300 ml can be observed without the need of surgical intervention was also found as an additional conclusion. In patients with blunt TT, chest physiotherapy is reported to have favorable effects on late-term complications, such as atelectasis and pneumonia.[15] It is also reported that postural drainage should not be performed, and percussion maneuvers should be carefully performed in patients with RF.[16] We did not perform these maneuvers to our patients. The powerful inspiration and coughing maneuvers cause a sudden expansion in chest volume and change the ICS distances in patients with RF. This situation may cause the bone fragments of the fractured ribs to move and cause tension and rupture of the underlying intercostal vessels. This may also cause lung parenchymal injury and complications, such as delayed hemopneumothorax, especially in patients with displaced RF. Chest physiotherapy is found to increase the incidence of delayed hemothorax in patients with RF secondary to blunt TT in our study, which is also found to be statistically significant. Because of this, we believe that chest physiotherapy should be carefully performed in patients with additional injuries and diseases, such as lung contusion and COPD in which additional complications, such as atelectasis and pneumonia may quickly develop. To prevent such complications, we believe that patients who have three or more RF should be closely monitored and treated in hospital. The limitations of this study are that this study involves both patients treated in outpatient clinics and the patients who were hospitalized, which may cause a heterogenous distribution among cases and that there are not many studies that encompass the adverse effects of chest physiotherapy on blunt thoracic trauma that could support our findings.

Conclusion As a conclusion of this prospective research study in which the effects of chest physiotherapy on the complications in patients with isolated RF secondary to blunt TT, chest physiotherapy increased the incidence of delayed hemothorax in patients who had three or more RF. There was no effect of chest physiotherapy on the development of delayed hemothorax in patients with less than three RF. In addition to these minimal amounts of hemothorax (<300 ml) spontaneously regressed if the proper follow-up procedures are implemented. Delayed hemothorax secondary to blunt TT 536

is also found to prolong the hospital stay of the patients. In the light of them, we believe that if chest physiotherapy is to be performed, it should be performed carefully in patients with three or more RF in hospital conditions because of its possible risks. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: T.A.; Design: T.A., İ.E.G.; Supervision: T.A., M.K.; Materials: T.A., İ.E.G.; Data: T.A., İ.E.G.; Analysis: T.A., M.K.; Literature search: İ.E.G., T.A., M.K.; Writing: İ.E.G., T.A.; Critical revision: T.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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Alar et al. The effects of AT and CP on the complications of the patients with RF that arise from blunt chest trauma ham MB, et al. To drain or not to drain? Predictors of tube thoracostomy insertion and outcomes associated with drainage of traumatic hemothoraces. Injury 2015;46:1743−8. 15. Simon BJ, Cushman J, Barraco R, Lane V, Luchette FA, Miglietta M, et

al; EAST Practice Management Guidelines Work Group. Pain management guidelines for blunt thoracic trauma. J Trauma 2005;59:1256−67. 16. Ciesla ND. Chest physical therapy for patients in the intensive care unit. Phys Ther 1996;76:609–25.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Künt toraks travması sonucu izole kot fraktürü gelişen hastalarda analjezik tedavi ve solunum fizyoterapisinin komplikasyonlara etkisi Dr. Timuçin Alar,1 Dr. İsmail Ertuğrul Gedik,2 Dr. Murat Kara3 Çanakkale Onsekiz Mart Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, Çanakkale Erzurum Bölge Eğitim ve Araştırma Hastanesi, Göğüs Cerrahisi Kliniği, Erzurum 3 İstanbul Üniversitesi İstanbul Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, İstanbul 1 2

AMAÇ: Bu ileriye yönelik çalışmanın amacı künt toraks travmaları nedeniyle izole kot fraktürü gelişen olgularda solunum fizyoterapisi ve ağrı kontrolünün, olası komplikasyonlardan hemotoraks ve/veya pnömotoraks gelişim riski üzerine etkisinin araştırılmasıdır. GEREÇ VE YÖNTEM: Bu ileriye yönelik çalışmaya Çanakkale Onsekiz Mart Üniversitesi Tıp Fakültesi Hastanesi Acil Servis ve Göğüs Cerrahisi Polikliniği’ne, künt toraks travması sonrası ilk 24 saat içinde başvuran ve izole kot fraktürü tespit edilen hastalar alındı. Kot fraktürü olan hastalardan ilk başvuru anında hemotoraks, pnömotoraks, yelken göğüs, atelektazi, pnömoni, akciğer kontüzyonu gibi ek yaralanması olmayan hastalar çalışmaya dahil edildi. Hastalar, kapalı zarf usulü sadece analjezik tedavi verilecek hastalar (Grup A) ve analjezik tedavi ile birlikte solunum fizyoterapisi verilecek hastalar (Grup B) olarak iki ayrı gruba ayrıldı. Birinci ve ikinci kot fraktürü saptanan olgular ile üç veya daha fazla kot fraktürü saptanan ve ek organ yaralanması olmayan hastalar göğüs cerrahisi kliniğine, ek organ yaralanması olanlar ise ilgili kliniklere yatırılarak takibe alındı. Bu kriterlerin dışında kalan izole kot fraktürlü hastalar ise gerekli tedavileri düzenlenerek poliklinikten takip edildi. Olgular travmayı takip eden ilk hafta ve birinci ayın sonunda fizik muayene ve radyolojik incelemeler ile değerlendirildi. BULGULAR: Çalışmaya dahil edilen 114 hastanın yaşları ortalama 56.3±16.4 (22–87) olarak bulundu. Hastaların 37’si (%32.5) kadın, 77’si (%67.5) erkekti. A ve B gruplarına 57’şer hastadan oluştu. Hastaların en sık geçirdikleri travma %31.6 ile aynı seviyeden düşme idi. Hastaların kot fraktürü sayılarının ortalaması 2.6±0.7 (1–10), ortanca sayı 1.5 olarak bulundu. Bu 114 hastanın 52’si (%45.6) hastanede yatarak tedavi edildi. Çalışmaya alınan hastaların yatış süreleri incelendiğinde hastaların ortalama yatış süresi 4.0±1.1 idi. Tedavi ve takipleri sonucunda çalışmaya alınan 114 hastanın 28’inde (%24.6) kot fraktürü gelişen tarafta plevral efüzyon saptandı. Hastalarda plevral efüzyon gelişme durumunun gruplara göre dağılımı incelendiğinde B grubundaki hastalarda (%43.9) A grubundaki hastalardan (%5.3) istatistiksel olarak anlamlı şekilde daha fazla plevral efüzyon gelişimi izlendi (p<0.0001). Çalışmamızda takipler sonucunda A grubundaki hiçbir hastaya müdahale gerekmezken, B grubundaki dört hastaya hemotoraks tanısıyla tüp torakostomi uygulandı (p<0.05). TARTIŞMA: Çalışmamızda künt toraks travması sonucu izole üç ve daha fazla kot fraktürü gelişen hastalarda solunum fizyoterapisi uygulamalarının gecikmiş hemotoraks gelişme riskini önemli derecede artırdığı, minimal hemotoraksların (<300 ml) uygun takip prosedürlerine uyulduğu takdirde spontan regrese olabileceği ve ek cerrahi müdahaleye gerek olmayabileceği tespit edilmiştir. Künt toraks travması sonucu üç ve daha fazla kot fraktürü olan hastalara eğer solunum fizyoterapisi uygulanması planlanıyorsa hastaların hastaneye yatırılarak takip ve tedavi edilmesi olası riskleri içeren ek komplikasyonlar gelişebilmesi açısından önerilebilir. Anahtar sözcükler: Hemotoraks; kot fraktürü; künt toraks travması; solunum fizyoterapisi. Ulus Travma Acil Cerrahi Derg 2020;26(4):531-537

doi: 10.14744/tjtes.2019.26356

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ORIGIN A L A R T IC L E

Comparison of post-operative outcomes of graft materials used in reconstruction of blow-out fractures Serdar Düzgün, M.D.,1 1

Bahar Kayahan Sirkeci, M.D.2

Department of Plastic and Reconstructive Surgery, Yüksek İhtisas University Faculty of Medicine, Liv Hospital Ankara, Ankara-Turkey

Department of Ear Nose Throat and Head and Neck Surgery, Yüksek İhtisas University Faculty of Medicine, Liv Hospital Ankara, Ankara-Turkey

ABSTRACT BACKGROUND: Trauma to the face caused by assault or impact may cause internal orbital fracture. Increased intraorbital pressure without disruption of soft tissue integrity or causing a fracture line in orbital rims or orbital floor fractures described as “orbital blowout fracture”. Such fractures have been categorized as “pure blow-out fractures” in which only the orbital floor is affected, and “impure blow-out fractures” in which other maxillofacial bones such as zygoma, maxilla and nasoethmoid are also affected. Physical examination reveals periorbital edema and ecchymosis, subconjunctival hemorrhage, limitation of eye globe movements, diplopia, enophthalmos, dystopia, and infraorbital hypoesthesia. Reconstruction of the orbital bony structures is the most important issue to preserve the standard orbital functions and providing an aesthetic view. Although many surgical approaches have been defined in the literature regarding the attitude and timing of treatment, no consensus exists. In literature; many autogenous and alloplastic biomaterials have been recommended to correct orbital bone defects. METHODS: This study aims to compare postoperative outcomes of patients presenting with pure and impure blow-out fractures repaired with cartilage, bone grafts, titanium mesh or porous polyethylene implant. Sixty-four orbital floor fractures of 62 cases were included in this research who admitted to our clinic with maxillofacial trauma between 2011 and 2018. All patients underwent maxillofacial radiological examination; Waters radiography and also axial-coronal plane maxillofacial and orbital computerized tomography. RESULTS: Permanent, post-operative, vertical diplopia in extreme gazes was detected in 3 of 14 patients in whom the orbital floor was reconstructed with an iliac bone graft. Two of nineteen cases who underwent reconstruction using auricular conchal cartilage graft had vertical diplopia in extreme gazes four months after the operation. The implant extruded and became palpable in 2 of 15 patients in the porous polyethylene implant group. None of the patients in the iliac bone and conchal cartilage autograft groups was presented late postoperative enophthalmos according to the graft resorption. In titanium mesh group, 1 of eleven patients had permanent, postoperative vertical diplopia in extreme gazes. None of the patients in this group developed any donor area complications, infection, or implant extrusion. CONCLUSION: Results show that the auricular conchal cartilage graft was the best biomaterial used to repair defects smaller than 4 cm², where as titanium mesh was a good option to repair defects larger than 4 cm². However, selection of the optimal biomaterial to be used to repair orbital blow-out fractures should be made according to patient characteristics and preoperative findings, the severity of the injury, the cost of the biomaterial to be used, and surgeon’s expertise. Keywords: All-plastic biomaterials; autogenous grafts; blow-out fractures.

INTRODUCTION Cranio-maxillo-facial fractures involving the orbits are frequent, with a prevalence of up to 50%.[1] Since the 1960s, orbital fractures have been categorized into two groups –

“pure” and “impure” regarding the preservation of the orbital rim.[2] Pure orbital fractures are limited to the orbital walls, whereas impure orbital fractures involve the adjacent facial bones, such as in orbitozygomatic, naso-orbito-ethmoidal, Le Fort II or III, or panfacial fractures.[3]

Cite this article as: Düzgün S, Kayahan Sirkeci B. Comparison of post-operative outcomes of graft materials used in reconstruction of blow-out fractures. Ulus Travma Acil Cerrahi Derg 2020;26:538-544. Address for correspondence: Bahar Kayahan Sirkeci, M.D. Yüksek İhtisas Üniversitesi Tıp Fakültesi, Liv Hospital Ankara, Kulak Burun Boğaz ve Baş Boyun Cerrahisi Bölümü, Ankara, Turkey Tel: +90 312 - 329 10 10 E-mail: baharkayahan@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):538-544 DOI: 10.14744/tjtes.2020.80552 Submitted: 18.12.2019 Accepted: 06.05.2020 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Pure blow-out fractures constitute 2.8–21.4% of the maxillofacial injuries.[2,3] Physical examination reveals periorbital edema and ecchymosis, subconjunctival hemorrhage, limitation of eye globe movements, diplopia, enophthalmos, dystopia, and infraorbital hypoesthesia. Enophthalmos is defined as the posterior displacement of the eyeball due to volume changes in the bony orbit and the disruption of orbital content. Two to three millimeters of enophthalmos is clinically detectable, and more than 5mm is disfiguring.[4] Although there is not any strict consensus on the indications for surgical repair of orbital floor fractures, mechanical muscle compression causing diplopia is one of the surgical indications. This situation can be identified using the forced duction test or imaging techniques. Another indication is the persistence of progressive enophthalmos following resolution of trauma-induced edema. Many surgeons believe that defects more significant than 1 cm² require surgery as they cause enophthalmos.[4]

All patients underwent maxillofacial examination, waters radiography and also axial-coronal plane maxillofacial and orbital computerized tomography. Evaluation of the radiographic and physical examination results revealed a unilateral blow-out fracture in 60 of 62 patients and bilateral blow-out fractures in two patients (Fig. 1). Of the 64 orbital fractures, 26 were pure, and 38 were impure blow-out fractures. A pre-operative ophthalmology consultation was obtained for all cases. An ophthalmologist using a Hertel exophthalmometry assessed the existence of enophthalmos. 2 mm or more posterior displacement was stated as enophthalmos. Ocular examination showed diplopia in vertical gaze in 31 patients, diplopia plus enophthalmos in 11 patients, and isolated

Many conventional strategies have been used to correct posttraumatic enophthalmos. Many autogenous and alloplastic biomaterials have been recommended to correct bony orbit, such as autogenous bone grafts, cartilage grafts, fascia grafts and artificial prostheses (using absorbable or nonabsorbable materials).[2,5] Resorption of the graft, longer operation time, and donor area morbidity are the main factors limiting the use of autogenous grafts.[6–8] These drawbacks are especially prominent in bone grafts. For a partial solution to the inherent disadvantages of autogenous grafts, allogenic materials have also been used to correct bony orbit defects. Allografts used for this indication include lyophilized dura mater, demineralized bone, irradiated cartilage, irradiated fascia and acellular dermal matrix. An ideal implant material should be sterilizable, chemically inert, nonallergic, non-carcinogenic, biocompatible, easy-to-remove, malleable, cost-effective, and resistant to deformation and stress. Also, it should not induce a foreign body reaction or create a medium for the growth of microorganisms.[4,9–11] To allow radiographic evaluation, radio-opaque materials that do not form any artifacts are preferred. The main problems due to the use of these materials are infection and extrusion risks.

Figure 1. Bilayered image of the bilateral blow-out fracture.

This study aims to compare postoperative outcomes of patients presenting with pure and impure blow-out fractures repaired with cartilage, bone grafts, titanium mesh or porous polyethylene implant.

MATERIALS AND METHODS Sixty-four orbital floor fractures of 62 cases were included in this research who admitted to our clinic with maxillofacial trauma between 2011 and 2018. Forty-seven (76%) of the patients were male, and 15 (24%) were female, mean age was 32 years (ranging between 15–54 years). Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Figure 2. Upward gaze impairment.

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dystopia in nine patients, upward gaze impairment of a case is shown in Figure 2. In addition to the results from coronal orbital tomography, the surgical indications were the presence of diplopia, dystopia, enophthalmos, and accompanying fracture(s). Eleven patients had a routine physical examination but underwent surgery because orbital tomographic images showed a defect larger than 1 cmÂ˛ on the orbital floor. The median time from the trauma to the operation was eight days (ranging from two to 60 days). The clinical approach was to operate all patients within the first ten days after the trauma. However, seven patients were operated more than 15 days after the trauma because of the delayed presentation or concurrent medical conditions.

mesh implants were fixed to the lower orbital rim using two micro screws (Fig. 4). Shapes of all autologous and alloplastic implants were modified to fit the defect and orbital floor. After placement of the implant, eye globe movements were tested with the forced duction test. After determining that eye globe movements in all directions become unrestricted, canthopexy was performed to prevent post-operative lower eyelid retraction, and then the incision was closed with double layers of 5/0 polyglactin suture. Reduction and plaque-screw fixations of all fractures of other maxillofacial bones accompanying the orbital floor fracture were performed simultaneously with the orbital floor fracture reconstruction.

All patients went under general anesthesia for surgery. Using suspension sutures, traction was applied on the lower eyelid and using a subciliary incision; the muscle-skin flap was elevated, and the orbital floor was accessed. Releasing the orbital contents compressed within the defect as necessary exposed the defect. To reconstruct the orbital floor defects, iliac bone graft was used in 14 patients, auricular conchal cartilage graft was used in 19 patients, ultra-thin porous polyethylene sheet (0.85 mm thick) was used in 15 patients, and titanium mesh was used in 16 patients.

The suspension sutures in the lower eyelid were removed on the second day after surgery, and the patients were instructed to massage the eye to prevent lower eyelid retraction. The patients were followed postoperatively for six to 31 months, with a mean follow-up of 14 months. All patients had ophthalmology consultation at the follow-up to assess enophthalmos existence by Hertel exophthalmometry, even the late postoperative period.

RESULTS

The conchal cartilage graft (Fig. 3) was placed as the perichondrium facing through the maxillary sinus. The titanium

Permanent, post-operative, vertical diplopia in extreme gazes was detected in three of 14 patients in whom the or-

Figure 3. Harvested cartilage graft.

Figure 5. Maxillofacial CT left orbital bone graft postop. 6. months.

Figure 4. The titanium mesh placed to the orbital floor defect.

Figure 6. Extrusion of the medpor.

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and porous polyethylene implant to reduce the volume of the orbita after releasing the implant from the muscle. Postoperatively, the upper gaze limitation was improved, and enophthalmos was reduced. However, diplopia in straight gaze became permanent, maybe due to incomplete improvement of enophthalmos. The other patient with persistent upper gaze limitation underwent the second operation two months after the first operation. During the second operation, the adhesions between the porous polyethylene implant and the inferior rectus muscle were removed and, to prevent future adhesions, a tensor fascia lata graft was placed between the inferior rectus muscle and the implant. After the operation, the upper gaze limitation improved, but vertical diplopia persisted in functional gazes, perhaps because of inferior rectus injury. None of the patients in this group developed an infection.

Figure 7. Radiographic image of the implanted titanium mesh.

bital floor was reconstructed with an iliac bone graft. However, since eye globe movements were free in all directions in all of the three patients, diplopia was considered to be the result of muscle contusion. Orbital floor evaluation via maxillofacial CT is seen in Figure 5. Hematoma requiring drainage was developed at the donor area in two patients also in this group. All patients in whom iliac bone graft was used complained about severe pain at the donor area. None of the patients developed an infection or experienced implant extrusion.

In the titanium mesh group, one of eleven patients had permanent, post-operative vertical diplopia in extreme gazes (Fig. 7). Re-operation was not considered to be necessary for that patient. A post-operative infection developed in one diabetic patient in whom the orbital floor was almost completely defective and was reconstructed with a titanium mesh. The patient underwent reduction and fixation with a plaque-screw from the oral cavity for a fragmented fracture in the zygomaticomaxillary region at the same time. Purulent discharge was drained from the maxillary sinus. The site of infection was irrigated with antibiotics regularly, and also intravenous antibiotic therapy was given. The infection regressed, and it was not necessary to remove the titanium mesh. No implant extrusion was observed in any of the patients in this group.

Two of nineteen cases who underwent reconstruction using auricular conchal cartilage graft had vertical diplopia in extreme gazes four months after the operation. However, no surgical re-operation was scheduled since eye globe movements were free in all directions. None of the patients in this group developed any donor area complications, infection, or implant extrusion. The implant extruded and became palpable in two of 15 patients in the porous polyethylene implant group. In one of these patients, the extruded part of the implant was trimmed surgically, and the other patient refused reoperation (Fig. 6). Two patients suffered from permanent upper gaze limitation and vertical diplopia in functional gazes. One of these patients was re-operated one month after the surgery because of persistent enophthalmos. During the operation, it was noticed that there were severe adhesions between the inferior rectus muscle and the implant. Iliac bone graft was placed between the inferior rectus muscle

Enophthalmos was persisted in only one patient postoperatively among 11 patients who had preoperative enophthalmos. This patient had been operated one month after the trauma because of the concurrent medical conditions. The postoperative period of this patient whose orbital floor was reconstructed with porous polyethylene is mentioned before in the text. None of the patients in the iliac bone and conchal cartilage autograft groups was presented late postoperative enophthalmos according to the graft resorption. Biomaterials data are shown in Table 1.

Table 1. Biomaterials and its properties Bone Cartilage Porous polyethylene implant Titanium mesh

Easy malleability +

Extrusion risk

Infection risk

–

Donor area Durability CCost morbidity

Limitation of eye globe movements

+ ++++ ++++ –

+++ –

–

+++

–

+++

++++

–

++++

+++

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++ +++ –

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DISCUSSION There is not any consensus in the literature to clarify the best graft and the most suitable timing of reconstruction of internal orbital fractures. Many authors recommended the use of different synthetic and autogenous biomaterials, each with its advantages and disadvantages, for the reconstruction of orbital floor defects.[4,11–14] In the past, there was a common belief that bone grafts were the most appropriate implant materials for orbital floor reconstruction.[4,5,7] Autogenous bone grafts have been recommended under their ability to provide a more sustained and stable reconstruction. Bone graft donor areas include iliac crest, ribs, calvarium, the anterior wall of the maxilla, and mandible.[13,15] The iliac bone grafts used in our study to reconstruct the orbital floor; however, they have some disadvantages, including the long time required for dissection, the risk of hematoma and pain at the donor area, and more prominent resorption in the graft due to its enchondral origin.[4,13,16] Besides, it is difficult to shape the bone tissue to fit the contour of the orbital floor because of the rigidity. The advantages of auricular conchal cartilage are more evident because the donor area is closer to the operation field, and harvesting the graft is technically more comfortable and, since the scar is behind the ear, donor area morbidity is negligible.[17] Also, the concave shape of the auricular conchal cartilage is appropriate for the anatomy of the orbital floor, and its elastic and malleable structure facilitates adaptation of the cartilage graft to the defect.[4,12,16] Furthermore, resorption of cartilage grafts occurs less frequently than the resorption of bone grafts.[15] Moreover, the cartilage grafts increase mucosal regeneration when the perichondrium faces the maxillary defect.[13] Regarding both the advantages and the disadvantage of size limitation, conchal cartilage grafts are underutilized in orbital floor reconstructions.[16–18] Alloplastic materials are easy to obtain and are not subject to resorption. Synthetic materials are easy to use, but their costs and risks are debatable. Infections, extrusion of the material from the skin, or displacement of the material are the most common complications when synthetic materials are used to repair orbital blow-out fractures.[14–19] Among the alloplastic materials used in our study, the highest complication rate was observed with the porous polyethylene implant as it allows the ingrowth of adjacent tissues into the graft material. Although this is important for stabilization, it may lead to adhesion of the implant to the rectus muscle if the muscle sheath is damaged. Consequently, upper gaze limitation and diplopia developed in two cases of this group. This risk of complication means that a porous polyethylene implant is not suitable for orbital floor reconstruction in patients with a damaged inferior rectus muscle sheath. Besides, properties of the porous polyethylene implants do not prevent implant extrusion since the implants were extruded in two of these 542

patients. To avoid this particular complication, porous polyethylene implants work better if it is fixed to the orbital floor with a screw. Among alloplastic materials, the best results were obtained when titanium mesh implant was used. The most commonly used material, titanium, has the highest tensile strength despite easily bending, and it is the least corrosive of the metals. Often used in facial bones’ fixation, titanium has high biocompatibility with a low risk of infection. It is compatible with radiographic imaging. Titanium mesh is favorable because of a high level of backup and malleability, which allows it to fit large defects or defects involving the medial side of the orbital floor.[14,20,21] Gear et al.[21] reported good functional outcomes and minimal risk of infection in a 44-month follow-up study where orbital floor defects larger than 2 cm² were reconstructed with titanium mesh in fifty-five patients. Other studies in which titanium mesh was used have similarly reported none or minimal post-operative infection. We encountered no complications with the use of titanium mesh except for one patient who suffered from an infection. Synthetic titanium mesh was preferred, especially in patients with a large orbital floor defect in case cartilage graft could not be used.[22,23] The most common complications after surgical repair of orbital fractures include lower eyelid retraction and enophthalmos, which is usually related to an increase in orbital volume resulting from improper placement of the implant material on the orbital floor.[4,21] Since the orbital floor has a posterior cephalic slope, the implant must be placed in an appropriate anatomical position to fit precisely.[4,21,22] If not, the implant can displace into the maxillary sinus, resulting in an increase in orbital volume and enophthalmos, which is often resistant to corrective surgical interventions.[4] For these reasons, how the implant is placed is more important than the type of implant material that is placed. Effort should be put to restore the orbital volume and contour. It is mandatory to test eye globe movements with the forced duction test after placement of the implant. Results show that the auricular conchal cartilage graft was the best biomaterial used to repair defects smaller than 4 cm². It is an easy-to-use biomaterial that fits the anatomical shape of the orbital floor, resulting in minimal donor area morbidity, lower treatment costs, and satisfactory post-operative patient outcomes. Among the synthetic materials tested, titanium mesh was a good option to repair defects larger than 4 cm². It provides sufficient strength, is easy to use, and is associated with a lower rate of postoperative complications and favorable patient outcomes. However, selecting the optimal biomaterial to be used to repair orbital blow-out fractures should be made according to patient characteristics and preoperative findings, the severity of the injury, and the cost of the biomaterial to be used, and surgeon’s expertise. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.D.; Design: S.D., B.K.S.; Supervision: S.D.; Fundings: S.D.; Materials: B.K.S.; Data: B.K.S.; Analysis: B.K.S.; Literature search: B.K.S.; Writing: B.K.S.; Critical revision: S.D., B.K.S. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Blow-out fraktürleri onarımında kullanılan greft materyallerinin ameliyat sonrası sonuçlarının karşılaştırılması Dr. Serdar Düzgün,1 Dr. Bahar Kayahan Si̇ rkeci2 1 2

Yüksek İhtisas Üniversitesi Tıp Fakültesi, Liv Hospital Ankara, Plastik ve Rekonstruktif Cerrahi Kiliniği, Ankara Yüksek İhtisas Üniversitesi Tıp Fakültesi, Liv Hospital Ankara, Kulak Burun Boğaz ve Baş Boyun Cerrahisi Kiliniği, Ankara

AMAÇ: Yüze alınan travmalarda internal orbital hasar görülebilir. Artan intraorbital basınç ile yumuşak doku bütünlüğünü bozulmadan orbital rimde ya da orbita tabanında kırık oluşumuna “blow-out fraktürü” adı verilir. Yalnızca orbita tabanının etkilendiği kırıklar “saf blow-out fraktürü” adı verilirken, zigoma, maksilla ve nazoetmoid kemiklerin de etkilendiği kırıklar “saf olmayan, kompleks blow-out fraktürleri” olarak nitelendirilir. Fizik muayenede periorbital ödem ve ekimiz, subkonjonktival kanama, göz hareketlerinde kısıtlılık, diplopi,enoftalmi, distopi ve infraorbital hipoestezi bulguları görülebilir. Orbital kemik yapıların rekonstruksiyonu hem standart göz fonksiyonunun sağlanması hem de estetik görünüm için elzemdir. Cerrahi yaklaşım ve zamanlaması açısından birçok görüş olmasına rağmen bir konsensus oluşmamıştır. Literatürde, orbita kemik defektlerini düzeltilmesi için birçok otojen ve alloplastik biyomateryallerin kullanımı konusunda çalışmalar mevcuttur. GEREÇ VE YÖNTEM: Bu çalışmada, saf ve kompleks blow-out fraktürü olan, kartilaj ve ya kemik greftleri ile titanyum mesh ya da poroz polietilen implant kullanılarak orbital rekonstrüksiyonu yapılan olguların postoperatif sonuçları karşılaştırılmıştır. 2011–2018 yılları arasında kliniğimize maksillofasiyal travma ile başvuran 62 olgunun 64 orbital taban kırığı çalışmaya dahil edildi. Tüm hastalara maksillofasiyal muayene yapıldı, radyolojik olarak Waters radyografi ve ayrıca aksiyal-koronal düzlem maksillofasiyal ve orbital bilgisayarlı tomografi ile değerlendirildi. BULGULAR: İliyak kemik grefti ile rekonstrüksiyon yapılan 14 hastanın 3’ünde aşırı bakışta kalıcı, ameliyat sonrası, dikey diplopi saptandı. Aurikula konkal kartilaj grefti ile rekonstrüksiyon yapılan 19 olgunun ikisinde operasyondan dört ay sonra aşırı bakışlarda dikey diplopi mevcuttu. İmplant, gözenekli polietilen implant grubundaki 15 hastanın 2’sinde ekstrüde oldu ve palpe edilebilir hale geldi. İliyak kemik ve konkal karitlaj otogreft gruplarında hiçbir hastada greft rezorpsiyonuna göre geç postoperatif enoftalmi izlenmedi. Titanyum mesh grubunda 11 hastadan 1’inde aşırı bakışlarda kalıcı, ameliyat sonrası dikey diplopi mevcuttu. Bu gruptaki hiçbir hastada herhangi bir donör bölgesi komplikasyonu, enfeksiyon veya implant ekstrüzyonu gelişmedi. TARTIŞMA: 4 cm²’den küçük defektlere yol açan blow-out fraktürlerinde kullanılabilecek en iyi biyomateryal aurikula konkal kartilaj iken; titanyum mesh 4 cm²’den büyük defektleri onarmak için iyi bir seçenek olmuştur. Bununla birlikte, orbita blow-out fraktürlerini onarmak için kullanılacak optimal biyomateryalin seçimi hasta özellikleri ve preoperatif bulgulara, yaralanmanın ciddiyetine, kullanılacak biyomateryalin maliyetine ve cerrahın uzmanlığına göre yapılmalıdır. Anahtar sözcükler: Alloplastik biyomateriyaller; blow-out kırığı; otojen greft. Ulus Travma Acil Cerrahi Derg 2020;26(4):538-544

doi: 10.14744/tjtes.2020.80552

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ORIGIN A L A R T IC L E

Professional practice assessment for minor head injury management in emergency department and clinical impact of a simulation-based training: Interventional study (before/after) Pierre Vandingenen, M.D.,1 Anthony Chauvin, M.D.,2 Nicolas Javaud, M.D.,3 Daniel Aiham Ghazali, M.D.4 1

Emergency Department and EMS, University Hospital of Poitiers, Poitiers-France

Emergency Department and EMS, University Hospital of LariboisiĂ¨re, Paris-France

Emergency Department, University Hospital of Louis Mourier, Colombes-France

Emergency Department and EMS, University Hospital of Bichat, Paris-France

ABSTRACT BACKGROUND: Minor head injury is a frequent reason for consultation in the emergency department. The use of computed tomography (CT) has increased dramatically in patientsâ&#x20AC;&#x2122; care. Good time management implementation and interpretation are required. To study the level of agreement with recommendations for a minor head injury in emergency department management and the impacts of simulation-based training (SBT) on professional practice changes. METHODS: Evaluation of professional practice for patient care in an emergency department according to the recommendations of the French Emergency Medicine Society (SFMU) established in 2012 before and after an SBT, including theoretical and simulation courses. It was based on the analysis of time to carry out a CT scan. It was also based on analysis of adherence to brain and spine scan indications and to hospitalization criteria. RESULTS: The SBT carried out in the evaluation of the professional practices makes it possible to acquire the notion of urgency to obtain the CT Scan within one hour when the criteria are met (p=0.007). Rater reliability for agreement with the hospitalization recommendations was better after SBT (p=0.03, increased Kappa from 0.73 to 0.93). On the other hand, there appeared to be a lack of essential information in the medical file, such as time of onset of head trauma. CONCLUSION: Management of this type of patient appeared to be satisfactory. It can be improved by SBT on the basis of the SFMU 2012 consensus conference. There is a need to improve the software used by the emergency departments, which should include the time of trauma and recommendations. The association of the clinic and the biomarkers could help to limit the indications of the CT scan, and thus to have it organized more rapidly. Keywords: Cervical spine; CT scan; emergency medicine minor head injury; evaluation of professional practice; hospitalization.

INTRODUCTION Minor head injury (MHI) is a frequent reason for emergency treatment with an estimated incidence in Europe of 235 per

100,000 people.[1] When a patient is admitted to the emergency department (ED) for this reason, the primary goal of the emergency physician (EP) is to identify patients at risk for cranio-cerebral lesions based on anamnestic and clinical cri-

Cite this article as: Vandingenen P, Chauvin A, Javaud N, Ghazali DA. Professional practice assessment for minor head injury management in emergency department and clinical impact of a simulation-based training: Interventional study (before/after). Ulus Travma Acil Cerrahi Derg 2020;26:545-554. Address for correspondence: Daniel Aiham Ghazali, M.D. ED and EMS, University Hospital of Bichat, 46 Rue Henri Huchard, 75018 Paris, France. Tel: 0033140257761 E-mail: danielaiham.ghazali@aphp.fr Ulus Travma Acil Cerrahi Derg 2020;26(4):545-554 DOI: 10.14744/tjtes.2020.91589 Submitted: 19.06.2019 Accepted: 02.01.2020 Online: 15.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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and delay in patient care.[6] Thus, CT is at the center of a public health debate establishing rules of prescription for.[7–10] The management of MHI was defined in France by the 2012 consensus conference of the French Society of Emergency Medicine (SFMU).[9] It was based on the National Institute for Health and Clinical Excellence (NICE) recommendations.[11] In ED, a patient with MHI must receive an initial assessment within 15 minutes of arrival by the reception nurse or the EP.[12] Glasgow Coma Scale (GCS) should be specified (with details) during this initial evaluation.[13] In the ED of the University Hospital of Poitiers, there is a significant increase in the demand for scanners and especially CT-scan, while the radiology department cannot meet this demand. This situation contributes to very significant delays in obtaining the imagery and contributes to the saturation of the ED. An initial evaluation of professional practice in ED aimed to estimate the risk of cerebral or cervical spinal cord injury and to determine the indication of the CT and spinal scan as well as its completion time (Table 1). We detected a non-respect of the French recommendations.

teria.[2] The reference examination for the detection of these lesions is the computed tomography (CT) scan in bone and parenchymal sections.[2,3] It can detect 8% to 15% of non-neurosurgical intracranial hemorrhagic lesions and fewer than 1% of lesions requiring a neurosurgical remedy according to the studies.[4,5] Indeed, the number of CT scans increased by 80% between 2000 and 2005 in the USA.[6] In France, EDs have largely followed this trend with the resulting problems of radiation.[6] This growth of the use of the CT scan nonetheless leads to questions about compliance with the recommendations without precautionary effect facilitated by easy access to this imagery. This situation may lead to excessive prescriptions because of fear of medical error.[6] In addition, the contribution of an examination depends on good management of the time required to complete and interpret, and therefore on the use of the relevant examination within appropriate deadlines. However, access circuits to emergency CT scan lack fluidity. [6] At the same time, respect of the indications limits useless examinations and consequently overloads of the apparatuses Table 1. Indication of the CT scan in case of minor head injury Indications of the CT scan between 4 and 8 hours after the trauma

Indications of the CT scan between 4 and 8 hours after the trauma

• Focused neurological deficit

• Patients unable to perform

• Significant anomalies in the

• Amnesia facts more than 30

• GCS score <15 at 2 hours of

minutes before the trauma (retrograde amnesia)  • Loss of consciousness

active 45 ° neck rotation (if spinal mobilization can be

trauma

performeda)

• Suspicion of open fracture of the skull or embarrassment

• Cervical pain or contracture

• Any sign of fracture of

in a patient over 65 years

associated with

the base of the skull

• Trauma with high risk: fall of

- a traumatic mechanism:

or amnesia of the facts

(hemotympanum, bilateral

more than 1 m or five steps,

pedestrian overturned by a

periorbital bruise),

axial impacts on the head

motorized vehicle, patient

otorrhea or rhinorrhea of

(diving), high-energy collision

ejected from a vehicle or falling from a height of more than one meter

cerebrospinal fluid • More than one episode of vomiting in adults

the accident of car with simple

- or over the age of 65

• Post-traumatic convulsion

rear shock, no embarrassment

• Treatment with Vitamin K

in sitting position, walk

the skull or embarrassment

• GCS score <15 after CTscan, whatever the result • Impossibility of performing CT scan despite its indication (unavailability of CT scan, transiently non-cooperating patient) • Persistence of severe vomiting and/or headache

The maneuver can be done if

• Suspicion of open fracture of • Any sign of fracture of

scan

• Anticoagulant and/or antiplatelet treatment • Ethyl or medications poisoning

antagonists (VKA) or other

since the accident, absence

• Suspicion of mistreatment

anticoagulant medications

of cervical contracture or

• Other reasons: social

the base of the skull (hemotympanum,

secondary cervicalgia

isolation, unreliable surveillance externally

• bilateral periorbital bruise), otorrhea or rhinorrhea • of cerebrospinal fluid • >1 vomiting in adults • Coagulation disorder (anticoagulant and/or antiplatelet treatment) GSC: Glasgow coma scale; CT: Computed tomography.

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Moreover, in some cases of MHI, there is an indication of hospitalization for clinical monitoring (Table 1).[4] Education in the principles and practice of evidence-based practice is widely accepted as a core component of professional education for healthcare professionals.[14] Our hypothesis is that simulationbased training (SBT) for EP would enhance professional practice by improving indications and the time to obtain CT and spinal scan, as well as respect for hospitalization’s indications.

MATERIALS AND METHODS Setting This prospective, single-center, and interventional study analyzed the impacts of a simulation course on management of patients admitted to an ED for an MHI between 1 January 2017 and 31 July 2017. This study took place at the University Hospital of Poitiers, France. ED welcomes more than 40,000 patients each year.[15] It includes a medical team of 34 doctors and 10 residents. The first phase of this study took place from January 1st, 2017, to March 31th, 2017. The first phase in the present study aimed to analyze the management of MHI and to identify areas for improvement during the course. The second phase of the study took place from May 1, 2017 to July 31, 2017 after training of physicians and residents. The aim in the second phase was to analyze the clinical impacts of the SBT on MHI management.

Objectives In this study, the primary objective was to analyze the clinical impacts of theoretical training and simulation on the timeless characteristics of the CT scan according to the protocol on use of a scanner for an MHI, and based on the codified recommendations made by the SFMU.[4] Secondary objectives were to assess: - Impacts of the course on agreement with the protocol on the use of a scanner for an MHI, - CT scan indications and analysis of the outcome of patients who did not have a CT scan when it was indicated, - Hospitalizations for MHI, - Cervical spine scan carried out in patients with MHI, - Management of the patients having anticoagulant and/or antiplatelet, - Evaluation of the SBT.

Population Physicians and Residents Inclusion criteria: emergency physicians and residents working in the ED of the university hospital of the Poitiers. Non-inclusion criteria: EPs and residents who could not be trained. Exclusion criteria: emergency physicians and residents who never worked during one of the two assessment periods. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Patients Eligible patients were patients admitted for an MHI in the ED of the university hospital of the Poitiers over the period of this study. The inclusion criteria were patients aged 18 years or older who had an MHI according to the SFMU recommendations, following a fall, a road accident or an assault. The non-inclusion criteria were severe head trauma, head trauma with associated extra-cranial lesions. Exclusion criteria were non-exploitable data (coding error, unspecified schedule of the brain injury), discharge against medical advice, and other reasons.

Intervention We used an educational intervention to enhance uptake of a specific clinical protocol using the “GREET” reporting standards.[14]

Definitions MHI is defined as an acute brain injury resulting from mechanical energy to the head from external physical forces associated with at least one of the following criteria: 1) confusion or disorientation; 2) loss of consciousness for 30 minutes or less; 3) resolute post-traumatic amnesia estimated for less than 24 hours during ED consultation; 4) other transient neurological abnormalities, such as focal signs; 5) seizures and intracranial lesions that do not require surgery; 6) a Glasgow Coma Scale (GCS) score between 13 and 15, 30 minutes after the injury or later during the ED visit. The following time intervals were recorded: time (minutes) between the MHI and the arrival at the ED, time (minutes) before performing the scan.

Theoretical and Simulation Course The SBT was conducted in the ED by AG (principal investigator) and PV (investigator) who have a university pedagogic diploma and are Directors of a Teaching Centre of Emergency Cares, with over six years’ experience of teaching. The course was provided face to face with a ratio of four learners to one instructor. It was based on a 15-minute PowerPoint presentation (theoretical course) and two 60-minute simulated patient simulation sessions (practical course). The theoretical course presented a definition of MHI and risk for the patient if not correctly managed. Then, it addressed the 2012 consensus conference of the French Society of Emergency Medicine (SFMU) for MHI management.[4] Learning objectives were: concerning Indications of the CT scan between four and eight hours after the trauma, indications in the hour after immediate request, Indications of the cervical spine scan, and indication to hospitalization (Table 1). Finally, it incorporated the points of the recommendations not respected within the ED, aiming to focus on these points and their potential risk for the 547

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patient. This theoretical course was followed by a simulation session. Two scenarios were pre-established (the first one: a 20 years old helmeted biker and without antecedent, an accident at low speed in the city; the second one: an 86-year-old patient with anticoagulant who had a mechanical fall on the stairs). Each learner was an observer and participant in one of the two scenarios. Each 10-minute scenario was preceded by a briefing of five minutes and a debriefing of 15 minutes. At the end of the training, 15 minutes were dedicated to a summary, with the possibility of asking questions about MHI management. All in all, the training lasted 90 minutes. Written support summarizing recommendations for the management of MHI was issued at the end of the session (Table 1). This training was mandatory for all doctors and residents. The SBT was evaluated by the participants concerning satisfaction and self-assessment of knowledge acquisition and a written test before and after training, 10 minutes before and 10 minutes after the training (Appendix 1). Several training sessions were conducted over one month to train the entire team. Evaluation of professional practices was conducted over two periods of three months before (period 1) and after SBT (period 2). Period 2 began after all training sessions were completed. Physicians and residents were advised of the MHI management assessment in both periods but were not aware of the primary and secondary outcomes. The residents were asked during the two periods to immediately refer to the referring senior physician for all patients with an MHI they had seen so that they could manage the patient collaboratively.

Main Outcome The main outcome was the percentage of patients meeting the 1-hour or 8-hour imaging time frame and time frame for completion of imaging according to the time of MHI. Secondary outcomes were - concordance between management concerning the recommended prescription of CT scan and cervical spine scan - criteria for hospitalization for the surveillance of a minor brain injury - analysis of the subgroup of patients with anticoagulant and/or antiplatelet - objective evaluation of the SBT by a knowledge test before and after training and by self-assessment questionnaire.

Data Collection The data of the patients admitted for MHI to the ED were carried out by NJ and MSJ using the ED’s electronic medical record system RESURGENCES® database and its statistical tool using the S06.0 code (head injury)[16] over the period concerned. For each MHI, extracted data included: sex, age, mechanism, emergency arrival times, CT scan times, and clinical data. 548

Statistics All anonymized data were analyzed using Statview® 4.5 (SAS Institute Inc., Cary, NC). Quantitative variables were described by their median, 1st and 3rd interquartile range [Q1; Q3]. Qualitative variables were described by number and percentage (n, %). The comparative analysis of the quantitative variables used a Mann Whitney’s non-parametric U test. Chi² test was used to compare qualitative variables. Rater reliability for the level of agreement with recommendations used Cohen’s kappa. A value of p<0.05 was considered.

Ethics This study was considered as an evaluation of the professional practice by the Agence Nationale de Sécurité du Médicament (the French National Medication Safety Agency) and was approved by the ED committee on ethics of the University Hospital of Poitiers. In accordance with the instructions of the ethics committee, the patients were informed by the flyer. The emergency staff gave them an explanatory document. Then, the agreement of the patients (or family) was obtained verbally. All the data collected were recorded in the patient file with an anonymous number for each patient. This coding was independent of the identity of the participants and any information that could identify them. The doctors and the residents of the department were informed of the evaluation of the professional practices. The methodology was approved by the Statistic and Epidemiologic Research Center (INSERM-U1153), Sorbonne Paris Cité (Paris, France), and statistical analysis was performed independently from the investigators by AC.

RESULTS Population Emergency Physicians and Residents Thirty-four physicians and ten residents worked in the ED during both periods of this study. Thirty-two doctors and all residents were trained. Two doctors were off work during the training and were not included in this study. One doctor was excluded from this study, having left the service during the second period of this study. In total, the evaluation of professional practices involved 31 doctors. The level of experience of physicians averaged six years [2; 16].

Patients One hundred and sixty-seven patients were eligible for the first phase of the evaluation of professional practices before training (period 1) and 170 for the second phase following training (period 2). Ninety-two files were included in Period 1 and 83 in Period 2. Details are given in the flow chart (Fig. 1). The characteristics of the population studied during Period 1 and Period 2 are given in Table 2. The characteristics of the two excluded populations over the two periods were anaUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Vandingenen et al. Vandingenen et al. Professional practice assessment for minor head injury management in ED and clinical impact of a SBT

Period 1: 1st January to 31th March 2016

Period 2: 1st May to 31th July 2016

Assessed for eligibility: 171

Assessed for eligibility: 174 Non-inclusion criteria Severe head injury: 6 Non-isolated head injury: 5

Included patients: 160

Analyzed: 92

Exclusion criteria Coding error: 1 lack of information on the schedule of the traumatism: 62 Exit against medical advice: 1 Other reason: 4

Non-inclusion criteria Severe head injury: 4 Non-isolated head injury: 4 Included patients: 166

Analyzed: 83

Exclusion criteria Coding error: 4 lack of information on the schedule of the traumatism: 73 Exit against medical advice: 0 Other reason: 4

Figure 1. Flow chart.

lyzed because of a large number of exclusions. The excluded patients were similar in both periods: 37 men (49%) during period 1 and 41 (47%) during period 2. The average age over these two periods was 70 years [33; 84] and 69 years old, respectively [31; 83].

Main Outcome The timeliness of the CT scan was significantly improved by the training and implementation of the decision support protocol for scans to be completed within one hour. There was no difference for the time between trauma delay–emergency arrival in period 1 and period 2 (p=0.33) (Table 3). CT scan performed before H1 after request according to the decisional algorithm represented 31.8% of cases (7 of 22 cases) in period 1 vs. 73.7% of cases (17 out of 19 cases) in period 2 (p=0.007). The number of CT scans indicated and performed in concordance with the consensus conference between H4 and H8 after the trauma was 55.6% (15 out of 27 cases) in Table 2. Patient characteristics Characteristic

Period 1

Period 2

Demographic characteristics, n (%)

Population

Median age, [Q1; Q3]

Male sex

92 (100)

83 (100)

69 [35; 82] 71 [41; 84] 47 (51)

42 (51)

68 (74)

60 (73)

Minor head injury mechanism, n (%)

Fall

Road accident

9 (10)

6 (7)

Aggression

14 (15)

16 (19)

Other

1 (1)

Legend: [Q1; Q3]: 1st and 3rd interquartile range; MHI: minor head injury; Period 1: assessment before the course; Period 2: assessment after the course.

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period 1 vs. 65.5% (17 of 26 cases) (p=0.46) in period 2. The times taken to perform the CT scan (in minutes) during the two periods are given in Table 3. These delays were significantly improved for the scans to be performed within one hour (p=0.014) during period 2 compared to period 1. There was no difference for the patients having to have the scanner within eight hours following the trauma (p=0.23).

Secondary Outcomes Indications of CT scan were considered correct if it was performed when indicated or not performed if it was not recommended. The CT scan indications were correct in 83.7% of the cases during period 1 and in 85.5% of the cases during period 2. In period 1, 10 patients did not have the CT scan, whereas it should have been done. For nine patients who could be contacted directly or through the GP, there was no complication. During period 2, seven patients did not have the scanner as recommended. One of them was hospitalized one day later for monocular blindness related to hemorrhage affecting the area of the optic nerve. For patients with anticoagulants or antiplatelet, there was 95.3% (37 out of 39) compliance with the indications during period 1 and 96.1% (38 out of 40) during period 2 (p=0.98). Indications for hospitalization to monitor MHI when justified were significantly improved in period 2 compared to period 1 (p=0.03). Non-performance of cervical imaging when it was not indicated was also improved in period 2 (p=0.04) (Table 4a). All hospitalization situations that were not performed while recommended were those of patients with antiplatelet. Cohen’s kappa was higher for all items in period 2 than in period 1, especially for hospitalization recommendations (0.73 in period 1 vs. 0.93 in period 2) (Table 4b).

DISCUSSION SBT significantly improved the time needed for “urgent” CT 549

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Table 3. The timeless characteristic of CT-scan in case of minor head injury Characteristic

Period 1

Period 2

CT scan correctly indicated

Required within 1 hour (n)

Required within 8 hours (n)

Number of CT scan carried out

Within 1 hour, n (%)

7 (31.8)

17 (73.7)

0.007

Within 8 hours, n (%)

15 (55.6)

17 (65.5)

0.46

99 [46; 150]

60 [39; 91]

0.014

Time in minutes

Required CT-scan in the hour after immediate request, Median time [Q1; Q3]

Required CT-scan before 8 hours after the trauma, Median time [Q1; Q3]

499 [271; 593]

400 [235; 518]

0.23

Delay Trauma â&#x20AC;&#x201C; emergency arrival, Median time [Q1; Q3]

131 [74; 154]

144 [84; 169]

0.33

Legend: [Q1; Q3]: 1st and 3rd interquartile range; Period 1: assessment before the course; Period 2: assessment after the course. CT: Computed tomography.

Table 4. Analysis of the indications to perform or not CT scan and cervical spine scan, and to monitor patients in case of minor head injuries before and after simulation-based training for emergency physicians and residents (a) Percent agreement

Required

Period 1

Not required

Period 2

Period 1

Period 2

CT scan

In theory (n)

In practice (n)

p 0.61 1

Cervical spine scan

In theory (n)

In practice (n)

p 0.40 0.04

Hospitalization

In theory (n)

In practice (n)

p 0.03 1

(b) Rater reliability using Cohenâ&#x20AC;&#x2122;s kappa

Theory (Period 1)

Theory (Period 2)

Required

Not required

Required

Not required

Carried out

Not carried out

Kappa 0.66

CT scan in practice

26 0.70

Cervical spine scan in practice

Carried out

Not carried out

Kappa 0.41

Hospitalization in practice

Carried out

0.51 2

Not carried out

Kappa 0.76 0.93

CT: Computed tomography.

scans to be performed within one hour of medical prescription. On the other hand, the course did not show any improvement in the time taken for CT scan to be performed 550

between four and eight hours after the head trauma. SBT also helped to make EPs more aware of the criteria for hospitalization and the criteria of gravity requiring appropriate Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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monitoring. The training significantly limited unjustified spinal imaging. Participants were satisfied with the training, which objectively improved their theoretical knowledge. Our study showed that SBT based on an initial evaluation of professional practices significantly shortened the time to perform a CT scan in MHI. The circumstances of head trauma occurrence were dominated by falls (74% in the first phase and 73% in the second phase), as described in some European studies.[17–19] Despite the existence of recommendations on the management of cranial trauma and prescription rules for scan, its application was not always respected; they were observed in almost 85% of cases. Even if strict adherence to the guidelines does not provide full protection against malpractice claims, its application improves the quality of management in an ED and reduces adverse outcomes. A very recent retrospective study based on Canadian CT guidelines[20] noted an unjustified number of CT scans of 10.9% overall and 37.3% for the patients under 65.[21] Another prospective multicenter study estimated this rate at 27%.[22] An American, retrospective study assessed compliance with the rules adopted by the American College of Emergency Medicine for prescribing the CT scan in case of minor brain injury, and it showed that the rules were applied for 75.5% of the patients.[23] The decision of whether or not to perform a CT scan notwithstanding knowledge of the consensus conference on minor brain injury management may be influenced by clinical and non-clinical factors.[24–26] Such management decisions have an impact on the functioning of a department: a significant increase in the use of CT in traumatic conditions over the past decade has resulted in longer times in ED for patients, as well as increased health care costs and unnecessary exposure to irradiations.[27] The notion of urgency to scan within one hour after prescription, when the relevant criteria were fulfilled, was accepted. [4] However, this was not the case concerning the CT scan to be carried out between four and eight hours following MHI. Several parameters could intervene: the time of head trauma may not have been noted. Our analysis made it possible to identify the first area in need of improvement. The software package could be enhanced by adding an alert or a time slot so that this information is obligatorily notified and not lost. Moreover, access to the support given during the training, posters and computerized access to the protocol recalling recommendations for MHI management (Table 1) in emergencies should be set up.[4] Another difficulty could consist of access to the scanner extraneous to the particular case allowing a scan to be performed within one hour. Access circuits to emergency CT scans lack fluidity (busy hours on weekdays, absence of dedicated machines, organizational problems that make emergencies interfered with programmed activity on the scanner).[6] In addition, this access can be slowed by the involvement of non-emergency responders, such as the stretcher-bearer, the radiological manipulator and the radiologist himself, who may not be sufficiently aware of this notion of delay. Several axes could be envisaged to improve the Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

fluidity of the circuit from the patient to the scanner. First, this training could be extended to the radiology department. Actions could be taken to simplify the scanner access circuit. For example, some emergency and radiology departments have recommended bringing patients to radiology without prior discussion between an emergency physician and a radiologist for a CT scan. This practice, currently customary for standard X-rays, would limit the elements rendering this examination difficult to perform within the recommended time limits. Authors have suggested the use of biomarkers, such as the S-100 ß protein assay in adults as an aid to the diagnosis of lesions in case of head trauma;[28,29] they have shown a very strong negative predictive value, close to 100%.[30] Routine use of this marker would quickly rule out any brain damage, at no risk for the patient, and thereby avoid approximately 30% of unnecessary CT scan.[30] However, this biomarker rapidly decreases and quickly loses its negative predictive value and sensitivity if not used early.[31] Through the initial evaluation, this study determined areas needing improvement. First, the undiagnosed complication in one patient due to lack of a CT-scan confirmed the need for strict compliance with the recommendations. In addition, the first phase of the study revealed non-compliance with the indications for spinal imaging and hospitalization. This analysis helped to focus on these important points during the training. The scores significantly improved on account of the training, and they were confirmed by a change in professional practice during the second, evaluated phase of the study, as well as the clinical impacts for the patient. Few studies have analyzed the clinical impacts of an SBT. In Kirkpatrick’s pyramid, there are 4 levels of evaluation for a course: level 1: satisfaction of the participants, level 2: acquisition of knowledge, skills, and attitude, level 3: changes in professional practices, and level 4: clinical impacts for the patient.[32,33] Level 4 (patient outcomes) is poorly studied in studies evaluating training, including simulation.[34,35] In addition to the improvement in CT scan times, other clinical impacts on the patient have been observed: respect for hospitalization criteria and conditions for cervical spine scan. A very recent study has shown that in the anticoagulant or antiplatelet population, the error was more related to the indication of hospitalization than to CT scan indication.[36] Our SBT revealed these errors and corrected them during simulation training. Based on Cohen’s kappa interpretation,[37] it was improved from the moderate level in period 1 to almost perfect level in period 2 meaning that rater reliability for the level of agreement with the recommendations was better after SBT. However, even after the training, there was one case of non-hospitalization despite antiplatelet treatment. Alert implementation in the software used in the ED in case of antiplatelet or anticoagulant treatment could help to limit this type of error. Easier access to the consensus conference in the software could also help to systematize compliance with the recommendations. Finally, this evaluation revealed that 39.7% of patient data in period 1 and 46.3% in period 2 could not be used due to lack of information. This was related to the trauma schedule, in which four of the records failed to 551

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report on clinical examination, and only gave CT scan results. Indeed, they could not determine the time elapsed between the trauma and the use of the scanner, thereby leading to undetected errors.

Limitations This monocentric study limits its external validity.[23,38] This study was carried out in a university hospital center where the CT scan is not performed without prior discussion between emergency physician and radiologist. These data cannot be generalized to hospitals where the CT scan is more systematically carried out. Finally, some general hospital centers only have one emergency doctor (especially during the night). Thus, time elapsed could be higher. Another limitation of this study was the change of residents during the study period. Nevertheless, to attenuate this bias, the residents who participated in period 1 and 2 had a similar experience, received the SBT, and were asked to immediately refer to the EP for each patient with MHI.

Conclusion Clinical impacts of SBT on patients with MHI were assessed: an SBT combining theoretical course and practical simulation significantly improved MHI management. Areas for future improvement concern CT scan to be performed within eight hours and the contents of medical records, including schedules. Improvements to the software used in EDs, with access to consensus conferences and visual alarms, could help. This evaluation of professional practices has shown that although the indications for CT scan appear to be accepted, there is a lack of performance concerning strict compliance with deadlines, as well as indications for cervical scan and hospitalization when monitoring is required. Availability of Supporting Data: The data supporting statistic findings are included in the manuscript. Please contact the corresponding author for other data requests. Ethics Committee Approval: This study was considered as an evaluation of the professional practice by the Agence Nationale de Sécurité du Médicament (the French National Medication Safety Agency) and did not need ethical approval. It was approved by the local Emergency Department committee on ethics of the University Hospital of Bichat. All patients were verbally informed that their medical data should be used for the present study under an anonymous number. Data were not used in case of patient refusal. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: D.A.G.; Design: D.A.G.; Supervision: D.A.G.; Materials: P.V., D.A.G.; Data: P.V.; Analysis: D.A.G., A.C.; Literature search: P.V., N.J., D.A.G.; Writing: P.V., D.A.G.; Critical revision: A.C., N.J. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. 552

REFERENCES 1. brain injury epidemiology in Europe. Acta Neurochir (Wien) 2006;148:255–68. 2. Mishra RK, Munivenkatappa A, Prathyusha V, Shukla DP, Devi BI. Clinical predictors of abnormal head computed tomography scan in patients who are conscious after head injury. J Neurosci Rural Pract 2017;8:64–7. 3. Stein SC, Ross SE. Minor head injury: A proposed strategy for emergency management. Ann Emerg Med 1993;22:1193–6. 4. Jehlé E, Honnart D, Grasleguen C, Bouget J, Dejoux C, Lestavel P, et al. Minor head injury (Glasgow Coma Score 13 to 15): triage, assessment, investigation and early management of minor head injury in infants, children and adults. Ann Fr Med Urg 2012;2:199–214. 5. Bruns JJ Jr, Jagoda AS. Mild traumatic brain injury. Mt Sinai J Med 2009;76:129–37. 6. Schouman-Claeys E. Emergency imaging and CT. [Article in French]. J Radiol 2007;88:529–30. 7. Stiell IG, Wells GA, Vandemheen K, Clement C, Lesiuk H, Laupacis A, et al. The Canadian CT Head Rule for patients with minor head injury. Lancet 2001;357:1391−6. 8. Smits M, Dippel DW, de Haan GG, Dekker HM, Vos PE, Kool DR, et al. Minor head injury: guidelines for the use of CT--a multicenter validation study. Radiology 2007;245:831−8. 9. Haydel MJ, Preston CA, Mills TJ, Luber S, Blaudeau E, DeBlieux PM. Indications for computed tomography in patients with minor head injury. N Engl J Med 2000;343:100–5. 10. Miller EC, Holmes JF, Derlet RW. Utilizing clinical factors to reduce head CT scan ordering for minor head trauma patients. J Emerg Med 1997;15:453–7. 11. National Collaborating Centre for Acute Care (UK). Head Injury: Triage, Assessment, Investigation and Early Management of Head Injury in Infants, Children and Adults. London: National Collaborating Centre for Acute Care (UK); 2007. 12. French Society of Emergency Medicine. Repository 2004 for the triage nurse (Référentiel IOA). Available from: URL: www.sfmu.org/upload/ referentielsSFMU/ioa2004.pdf. Accessed April 8, 2018. 13. Türedi S, Hasanbasoglu A, Gunduz A, Yandi M. Clinical decision instruments for CT scan in minor head trauma. J Emerg Med 2008;34:253–9. 14. Phillips AC, Lewis LK, McEvoy MP, Galipeau J, Glasziou P, Moher D, et al. Development and validation of the guideline for reporting evidencebased practice educational interventions and teaching (GREET). BMC Med Educ 2016;16:237. 15. Official website of the University Hospital of Poitiers. Available from: URL: http://www.chu-poitiers.fr/specialites/urgences/en/. Accessed April 8, 2018. 16. WHO. International Statistical Classification of Diseases and Related Health Problems 10th Revision. 2016. Available from: URL: http:// apps.who.int/classifications/icd10/browse/2016/en#/. Accessed April 8, 2018. 17. Alaranta H, Koskinen S, Leppänen L, Palomäki H. Nationwide epidemiology of hospitalized patients with first-time traumatic brain injury with special reference to prevention. Wien Med Wochenschr 2000;150:444–8. 18. Andersson EH, Björklund R, Emanuelson I, Stålhammar D. Epidemiology of traumatic brain injury: a population based study in western Sweden. Acta Neurol Scand 2003;107:256–9. 19. Kleiven S, Peloso PM, von Holst H. The epidemiology of head injuries in Sweden from 1987 to 2000. Inj Control Saf Promot 2003;10:173–80. 20. Papa L, Stiell IG, Clement CM, Pawlowicz A, Wolfram A, Braga C, et al. Performance of the Canadian CT Head Rule and the New Orleans

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Vandingenen et al. Vandingenen et al. Professional practice assessment for minor head injury management in ED and clinical impact of a SBT Criteria for predicting any traumatic intracranial injury on computed tomography in a United States Level I trauma center. Acad Emerg Med 2012;19:2−10. 21. Klang E, Beytelman A, Greenberg D, Or J, Guranda L, Konen E, et al. Overuse of Head CT Examinations for the Investigation of Minor Head Trauma: Analysis of Contributing Factors. J Am Coll Radiol 2017;14:171−6. 22. Ro YS, Shin SD, Holmes JF, Song KJ, Park JO, Cho JS, et al; Traumatic Brain Injury Research Network of Korea (TBI Network). Comparison of clinical performance of cranial computed tomography rules in patients with minor head injury: a multicenter prospective study. Acad Emerg Med 2011;18:597−604. 23. DeAngelis J, Lou V, Li T, Tran H, Bremjit P, McCann M, et al. Head CT for Minor Head Injury Presenting to the Emergency Department in the Era of Choosing Wisely. West J Emerg Med 2017;18:821−9. 24. Melnick ER, Shafer K, Rodulfo N, Shi J, Hess EP, Wears RL, et al. Understanding Overuse of Computed Tomography for Minor Head Injury in the Emergency Department: A Triangulated Qualitative Study. Acad Emerg Med 2015;22:1474−83. 25. Miglioretti DL, Johnson E, Williams A, Greenlee RT, Weinmann S, Solberg LI, et al. The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr 2013;167:700−7. 26. Smith-Bindman R, Lipson J, Marcus R, Kim KP, Mahesh M, Gould R, et al. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med 2009;169:2078−86. 27. Korley FK, Pham JC, Kirsch TD. Use of advanced radiology during visits to US emergency departments for injury-related conditions, 1998-2007. JAMA 2010;304:1465–71. 28. Beaudeux JL, Laribi S. S100B protein serum level as a biomarker of minor head injury. [Article in French]. Ann Biol Clin (Paris) 2013;71:71−8.

29. Springborg JB, Undén J, Ingebrigtsen T, Romner B. Brain injury marker S100B can reduce the use of computer tomography in minor head injuries--secondary publication. [Article in Danish]. Ugeskr Laeger 2009;171:978–81. 30. Laribi S, Kansao J, Borderie D, Collet C, Deschamps P, Ababsa R, et al; Stic-S100 Study Groupa. S100B blood level measurement to exclude cerebral lesions after minor head injury: the multicenter STIC-S100 French study. Clin Chem Lab Med 2014;52:527−36. 31. Zongo D, Ribéreau-Gayon R, Masson F, Laborey M, Contrand B, Salmi LR, et al. S100-B protein as a screening tool for the early assessment of minor head injury. Ann Emerg Med 2012;59:209−18. 32. Kirkpatrick DL. Evaluation of training. In: Craig RL, Bittel LR, editors. Training and Development Handbook. New York: McGraw Hill; 1967. p. 87–112. 33. Smidt A, Balandin S, Sigafoos J, Reed VA. The Kirkpatrick model: A useful tool for evaluating training outcomes. J Intellect Dev Disabil 2009;34:266–74. 34. Zendejas B, Brydges R, Wang AT, Cook DA. Patient outcomes in simulation-based medical education: a systematic review. J Gen Intern Med 2013;28:1078–89. 35. Ghazali DA, Choquet C, Casalino E. Simulation-based training for triage of HIV exposures in the emergency department. Med Educ 2019;53:521–2. 36. Chapin M. Assessment of minor head injuries in emergencies departments (Evaluation des traumatismes crâniens légers aux urgencies). Medical thesis 2016, University of Rouen, France. Available from: URL: https://dumas.ccsd.cnrs.fr/dumas-01381274/document. Accessed April 8, 2018. 37. McHugh ML. Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 2012;22:276–82. 38. Wennberg JE. Unwarranted variations in healthcare delivery: implications for academic medical centres. BMJ 2002;325:961–4.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Acil serviste hafif kafa travması yönetimi için profesyonel uygulamanın değerlendirilmesi ve simülasyon tabanlı eğitimin klinik etkisi: Girişimsel çalışma “öncesi-sonrası” Dr. Pierre Vandingenen,1 Dr. Anthony Chauvin,2 Dr. Nicolas Javaud,3 Dr. Daniel Aiham Ghazali4 Poitiers Üniversite Hastanesi, Acil Servis Bölümü ve EMS, Poitiers-Fransa Laribisière Üniversite Hastanesi, Acil Servis Bölümü ve EMS, Paris-Fransa Louis Mourier Üniversite Hastanesi, Acil Servis Bölümü, Colombes-Fransa 4 Bichat Üniversite Hastanesi, Acil Servis Bölümü ve EMS, Paris-Fransa 1 2 3

AMAÇ: Hafif kafa travması acil servise (AS) konsültasyon için sık başvurulma nedenidir. Bilgisayarlı tomografi (BT) kullanımı hastaların bakımını önemli ölçüde iyileştirmiştir. İyi bir zaman yönetimi ve yorumu gereklidir. Bu yazıda, AS yönetiminde hafif kafa travması önerilerine uyum düzeyi ve simülasyon temelli bir eğitimin (SBT) profesyonel uygulama değişiklikleri üzerindeki etkisi incelendi. GEREÇ VE YÖNTEM: Bir AS’de, SBT öncesinde ve sonrasında hasta bakımı için profesyonel uygulamanın 2012 yılında kurulan Fransız Acil Tıp Derneği’nin (Société Française de Médecine d’Urgence: SFMU) önerilerine göre teorik ve simülasyon kurslarını içeren değerlendirmesi yapıldı. BT taraması yapmak için zaman analizine, ayrıca beyin ve omurga tarama endikasyonlarına ve hastaneye yatış kriterlerine uyum analizine dayanıyordu. BULGULAR: Mesleki uygulamaların değerlendirilmesinde gerçekleştirilen SBT, kriterleri karşıladığında bir saat içinde BT taraması sonucunu alma açısından aciliyet kavramını edinmeyi mümkün kılmaktadır (p=0.007). SBT’den sonra hastaneye yatış önerilerine uyumuna ilişkin değerlendirici güvenilirliği daha iyi idi (p=0.03, Kappa’yı 0.73’den 0.93’e yükseltti). Öte yandan, tıbbi dosyada kafa travmasının oluş zamanı gibi temel bilgilerin eksik olduğu ortaya çıktı. TARTIŞMA: Bu tip hastanın yönetimi tatmin edici görünmektedir. SBT tarafından SFMU 2012 uzlaşı konferansı temelinde SBT uygulanarak bu durum geliştirilebilir. Acil servisler tarafından kullanılan ve travma zamanını ve önerileri içermesi gereken yazılımı geliştirmeye ihtiyaç vardır. Klinik ve biyobelirteçlerin birlikteliği BT taramasının endikasyonlarını sınırlamaya ve böylece daha hızlı organize edilmesine yardımcı olabilir. Anahtar sözcükler: Acil tıp; BT taraması; hafif kafa travması; hastaneye yatış; mesleki uygulamaların değerlendirilmesi; servikal omurga. Ulus Travma Acil Cerrahi Derg 2020;26(4):545-554

doi: 10.14744/tjtes.2020.91589

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Appendix 1: QUESTIONNAIRE PRE/POST-TRAINING Management of minor head injuries in Emergency Department

QUESTION 1: Check the correct answer(s) concerning the factors to be checked immediately (maximum within one hour of the request) • A: anticoagulant treatment • B: antiplatelet treatment • C: vomiting • D: GCS score <15 one hour after head trauma • E: post-trauma convulsions QUESTION 2: Check the correct answer(s) for the factors that should be taken into consideration to make cervical spine scan • A: fall of less than 5 steps • B: Inability to perform active rotation of the neck by 45° • C: patient over 65 years old • D: pain or contracture in a patient over 65 years old • E: 3 m drop QUESTION 3: Check the correct answer (s) for hospitalization criteria for minor head injuries: • A: impossibility to perform the brain scan even if the indication is required • B: associated intoxication (drug, alcohol, ...) • C: normal scan at 6 hours after head trauma • D: anticoagulant treatment • E: antiplatelet treatment QUESTION 4: Check the correct answer (s) for the risk factors leading to performance of a CT scan: • A: high kinetic energy in road traffic injury • B: patient over 65 years old • C: focused neurological deficit • D: amnesia of facts in a 40-year-old patient • E: otorrhagia QUESTION 5: Check the correct answer (s) for the management of patients with minor head injuries: • A: a pregnancy test must be performed beforehand in pregnant women if a CT scan is to be performed • B: in cervical trauma of medium gravity, cervical spine X-ray should be preferred • C: at least 24h monitoring is required for patients with head trauma if they have an anticoagulant or antiplatelet treatment • D: CT scan is mandatory in a patient with head trauma associated with drug intoxication • E: a head trauma with a normal early scan does not require monitoring RESPONSES 1. ACE 2. BDE 3. ABDE 4. ACE 5. C 6. C

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ORIGIN A L A R T IC L E

Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy Cemalettin Koç, M.D.,1 Sami Akbulut, M.D.,1 Barış Sarıcı, M.D.,1 Sezai Yılmaz, M.D.1

Ebru İnci Coşkun, M.D.,2

Department of Surgery and Liver Transplant Institute, İnönü University Faculty of Medicine, Malatya-Turkey

Department of Obstetrics and Gynecology, İnönü University Faculty of Medicine, Malatya-Turkey

ABSTRACT BACKGROUND: This retrospective study aims to compare the demographic and clinicopathological characteristics of the pregnant and non-pregnant patients who underwent appendectomy with a presumed diagnosis of acute appendicitis. METHODS: Between June 2009 and January 2019, 431 reproductive-aged of female patients underwent appendectomy with a presumed diagnosis of acute appendicitis. Patients were divided into two groups considering their pregnancy status: pregnant group (n=48) and non-pregnant group (n=383). Both groups were compared with respect to demographic, clinical and histopathological features. RESULTS: No statistically significant difference was found between pregnant and non-pregnant groups except total bilirubin level (p=0.019) and ultrasonographic findings (p=0.016). In the non-pregnant group, negative appendectomy and perforation rates were 26% and 10.5%, where these rates for the pregnant group were 20.8% and 4.2%. Sensitivity, specificity and accuracy rates of ultrasonography for the pregnant group were 50%, 100% and 58.5%, where these rates for the non-pregnant group were 67.3%, 57.9% and 65%. The pregnancy date was the first trimester in 52.1%, the second trimester in 29.2% and the third trimester in 16.7% of the pregnants. None of the term births (87.5%) resulted in neither a fetal nor a maternal complication. However, 12.5% of the preterm births resulted in neonatal mortality. CONCLUSION: Although not statistically significant, this study points out relatively lower rates of negative appendectomy and perforated acute appendicitis among pregnant patients, which is related to the overly attentive evaluation of pregnants admitted due to acute abdomen. Keywords: Acute appendicitis; appendectomy; obstetric complications; pregnancy; preterm labour.

INTRODUCTION Acute appendicitis (AAp) is among the leading causes of emergency unit admissions due to abdominal pain and appendectomy is among the world wide most performed surgical procedures.[1,2] Obstruction of appendix vermiformis lumen due to any cause triggers an inflammatory process that initially begins in epithelium progressing into serosa, resulting in classical sign and symptoms of AAp.[2] Lifetime real AAp risk varies from 5% to 20% and which is around 6.9% for women.[1,2]

AAp is one of the most frequent conditions of pregnant women requiring an emergent surgical procedure. AAp incidence during pregnancy varies from 1/800 to 1/1500 and has a relatively lower incidence compared with non-pregnant women of the same age.[3] Loss of appetite, nausea, and vomiting, abdominal pain are the cardinal signs and symptoms of AAp, which are frequently common in the normal physiological course of pregnancy.[4] Therefore, diagnosing AAp in a pregnant patient is challenging and 25% to 50% of patients are preoperatively underdiagnosed.[4] Delay in diagnosis or

Cite this article as: Koç C, Akbulut S, Coşkun Eİ, Sarıcı B, Yılmaz S. Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy. Ulus Travma Acil Cerrahi Derg 2020;26:555-562. Address for correspondence: Cemalettin Koç, M.D. İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya, Turkey Tel: +90 422 - 341 06 60 E-mail: ckoc_41@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):555-562 DOI: 10.14744/tjtes.2020.12544 Submitted: 19.09.2019 Accepted: 15.01.2020 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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underdiagnosis in pregnant patients results in perforation and peritonitis, which leads to unfavorable complications of early delivery, miscarriage, fetal loss, and maternal mortality.[4] This study presented aims, first of all, compare demographic, biochemical and histopathological features of pregnant and non-pregnant female patients admitted to our surgery clinic instruction with an initial diagnosis of AAp. The second aim is to present maternal and fetal complication following appendectomy among pregnant patients.

MATERIALS AND METHODS Between June 2009 and January 2019, the demographic, biochemical and histopathological features of the 48 pregnant patients who underwent appendectomy with presumed diagnosis of AAp at Inonu University Faculty of Medicine, Department of Surgery were analyzed retrospectively. This group was defined as the Pregnant group (n=48). A control group was created to compare with the pregnant group and this group was defined as non-pregnant group (n=383). The nonpregnant group consists of reproductive-aged (range: 18–45 years) female patients who presented to our emergency unit with abdominal pain at the same time frame and underwent appendectomy with the presumed diagnosis of AAp. Patients’ medical records were reviewed after obtaining approval from Inonu University institutional review board for non-interventional studies (Approval No:2019/4-41). Both groups were compared in terms of age (years), white blood cell (WBC), Neutrophil, Lymphocyte, Platelets, mean corpuscular hemoglobin (MCH), red cell distribution width (RDW), mean platelet volume (MPV), mean corpuscular volume (MCV), platelet distribution width (PDW), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), white blood cell to lymphocyte ratio (WLR), white blood cell to neutrophil ratio (WNR) bilirubin, appendix width (mm), appendix length (mm) and histopathological findings. Pregnancy is categorized into three phases of the first trimester (0–14 wk), second trimester (15–28 wk) and third trimester (29–42 wk).[5] Patients younger than 18 years of age are excluded from this study. Therefore, non-pregnant patients from 18 to 45 years of age are included in the control group for matching the age of the pregnant group. All patients admitted to the emergency unit with an initial diagnosis of AAp were evaluated with routine anamnesis (such as date of last menstrual period, sexual activity), blood β-hCG level and abdominopelvic ultrasonography (US) to rule out obstetrical and gynecological conditions. Demonstration of a non-compressible, aperistatltic tubular structure originating from cecum, with a blind end, anteroposterior diameter >6 mm in US evaluation is defined as AAp. Additionally, thickened intestinal wall, inflammation, increased echogenicity of surrounding mesenteric fatty tissue, heterogeneity, appendicolith, presence of either pericecal or 556

abdominal free fluid are considered of a diagnostic fact independent from the visual status of the appendix. Patients with a history of actual pregnancy status did not undergo a computerized tomography (CT) evaluation. Although magnetic resonance imaging (MRI) is among the examination techniques for differential diagnosis of AAp in pregnant patients, none of the patients at our institution underwent an MRI procedure. Concerning macroscopic and microscopic findings, pathological examination reports are classified as appendix vermiformis (without any evidence for inflammatory cell infiltration), lymphoid hyperplasia and acute appendicitis (simple appendicitis, perforated appendicitis, gangrenous appendicitis, phlegmonous appendicitis). Rare entities of granulomatous appendicitis, fibrous obliteration, mucocele, mucinous cystadenoma and carcinoid tumor are also classified. Antibioprophylaxy is given to all patients in the two groups. Patients with intraoperative diagnosis of appendix perforation, presence of periappendicular or pelvic fluid resembling to be infected received antibiotic treatment postoperatively. Centers for Disease Control and Prevention Guideline were considered in the evaluation of postoperative surgical site infections.

Specific Obstetric Assessment in Pre/Perioperative Period All patients with an initial diagnosis of AAp with a reproductive age were evaluated by an obstetrics and gynecology specialist. All of the pregnant patients underwent a vaginal examination to detect any ex utero haemorrhage, miscarriage material inside vagina or cervix. Pregnant patients in second and trimester were evaluated with the transvaginal US to measure cervical longitude and detect the presence of any cervical funneling. Pregnants in a suitable gestational week were evaluated with tocography to detect presence of uterine contraction and ultrasonographic foetal nonstress test to clarify the well-being of the foetus. Pregnants in the first trimester that are with a relatively higher risk for miscarriage received supplementary progesterone. Pregnants in the third trimester with uterine contractions pointing out increased risk for preterm delivery received tocolytic treatment and supplements to promote foetal pulmonary development. All of the pregnants received adequate perioperative hydration to prevent dehydration.

Statistical Analysis The statistical analyses were performed using IBM SPSS Statistics v25.0 (Statistical Package for the Social Sciences, Inc, Chicago, IL, USA). The quantitative variables were expressed as Mean±SD, Median and Min-Max. The qualitative variables were reported as number and percentage (%). Kolmogorov-Smirnov tests were used to assess normality distribution of quantitative variables. Mann-Whitney U test was used to compare the quantitative variables. Pearson ChiSquare and Fisher’s exact tests were used to compare qualitative variables. Sensitivity, specificity, positive predictive value, Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Koç et al. Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy

negative predictive value and accuracy value of ultrasonography in pregnant patients with presumed diagnosis of acute appendicitis were also measured. A p-value of less than 0.05 was considered statistically significant.

RESULTS Pregnant versus Non-pregnant Patients Undergoing Appendectomy A sum of 431 women in reproductive age varying from 18 to 45 underwent appendectomy with an initial diagnosis of AAp. Patients were grouped into two, according to their pregnancy status at the time of AAp diagnosis: pregnant group (n=48) and non-pregnant group (n=383). There was no statistically significant difference between the groups concerning age (p=0.710), WBC (p=0.956), neutrophil count (p=0.868), lymphocyte count (p=0.571), thrombocyte count (p=0.0.814), RDW (p=0.066), PDW (p=0.183), MCH (p=0.105), MPV (p=0.773), MCV (p=0.775), CRP (p=0363.), NLR (p=0.486), PLR (p=0.712), PNR (p=0.851), WLR (p=0.430), WNR (p=0.204), appendix length (p=0.581), appendix width (p=0.734), general histopathological findings (p=0.580), appendiceal perforation (p=0.204) and presence of histopathological AAp (p=0.429). On the other hand, there was a statistically significant difference between the groups for total bilirubin level (p=0.019) and diagnosis of AAp in US evaluation (p=0.016). Median bilirubin level was 0.58 mg/dL (mean±SD: 0.71±0.50) in the non-pregnant group, whereas it was 0.49 mg/dL (mean±SD: 0.58±0.53) in the pregnant group. US evaluation diagnosed AAp in 61% of 351 non-pregnant group, whereas this rate was 41.5% among 41 pregnant patients. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy rates for US in pregnants were 50.0 %, 100.0%, 100.0%, 29.1 % an 58.5 % in order, AAp and appendiaecal perforations for non-pregnant patients were 74% and 10.5% in order which were 79.2% and 4.2% for pregnant patients. In other words, negative appendectomy rates for non-pregnant and pregnant patients were 26% and 20.8% in order. None of the cases resulted in a surgical site or organ infection requiring either relaparotomy or percutaneous drainage. Only two cases in each group had superficial surgical site infection requiring simple drainage. Demographic, clinical and histopathological features of the two groups are given in Table 1, 2.

Obstetric Course of Pregnant Patients Undergoing Appendectomy A total of 13.734 deliveries were conducted at our obstetrical department during same time frame and an incidence of one case of appendectomy for preliminary diagnosis of AAp in 286 births. Also, pregnant women consisted of 11.1% of the reproductive-aged women who underwent appendectomy due to preliminary diagnosis of AAp. Among the 48 pregnants who underwent appendectomy, 25 (52.1%) pregnants were in first trimester, 14 (29.2%) pregnants were in second Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

trimester, remaining eight (16.7%) pregnants were in the third trimester of pregnancy. Among the 23 of the patients in the first trimester and 10 of the patients in the second trimester, appendectomy was performed using McBurney incision. Remaining two patients in the first trimester underwent laparoscopic appendectomy. Ten the second trimester patients and all of the third trimester patients underwent appendectomy via Rockey-Davis or pararectal incision, considering dimensions of the uterus and locational change of cecum. Following appendectomy, 42 (87.5%) of the pregnants gave vaginal birth, the remaining six (12.5%) of the pregnants admitted to the obstetrics clinic due to preterm delivery (3–8 weeks before gestational term). Among the preterm delivery pregnants, five of them gave birth via caserian section; one pregnant gave vaginal birth. Among the term deliveries, all of the babies were free of mortality and morbidity. Among the preterm delivery pregnants, one had diamniotic dichorionic twins and delivered two male babies on 28th week with a body weight of 1800 gr and 1900 gr. One of the preterm pregnants on 30th gestational week, the baby was delivered but died postpartum day 17 due to respiratory failure. Another preterm pregnancy on 22nd gestational week was terminated following the diagnosis of in-utero exitus of a 500 gr foetus. Mean birth weight of babies was 2950 gr (min-max:). As a result, 31 (64.6%) pregnants underwent a casearian section, and 17 (35.4%) delivered transvaginally.

DISCUSSION AAp is among the most frequent non-obstetrical conditions requiring surgical treatment. Frequency of pregnant patient those diagnosed AAp and underwent appendectomy varies from 0.18 to 10.56 per every 1000 pregnants. Our literature analysis of 67 published studies reveals that 11.198 of 11.556.461 pregnants underwent surgical exploration with a preliminary diagnosis of A Ap. In other words, the frequency of appendectomy per 1000 pregnants is 0.97 (Table 3). Acceptable negative appendectomy (NA) is among the most frequently emphasized issues, which has a reported rate vary from 0% to 50% in many studies. The general consensus for an acceptable NA rate is 10 to 25 %. However, newer studies report rates lower than 10% related to recent diagnostic instrumentation and scoring systems.[6–8] As Tubo-ovarian diseases are leading conditions resembling AAp, the NA rate is higher in female patients than in males. Literature review of the 14 published studies (n=98.933) comparing pregnant (n=3.971) and non-pregnant AAp (n=94.962) reveal that NA rates of pregnant women vary from 0% to 38% whereas NA rates of non-pregnant women vary from 0% to 21.8%. [4,5,9–20] In eight of these studies, NA was found to be higher in pregnant patients, whereas in three of these studies, NA was found to be higher in non-pregnant. Although it was not statistically significant, NA rates of pregnants were higher in 557

Koç et al. Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy

Table 1. Comparison of the pregnant and non-pregnant Acute appendicitis patients concerning clinical, biochemical and histopathological parameters Patients’ characteristics Age

Non–pregnant (n=383)

Pregnant (n=48)

Median (min–max)

28 (18–45)

27.5 (19–45)

0.710

White blood cell

12.4 (1.2–26.9)

12.4 (6.3–22.4)

0.956

Neutrophil

9.7 (0.4–22.9)

9.6 (2.4–30.8)

0.868

Lymphocyte

1.6 (0.2–7.8)

1.7 (0.5–14.8)

0.571

Platelets

251 (43–570)

246 (141–573)

0.814

Red cell distribution width

13.7 (11–33.3)

14.5 (11.9–24.2)

0.066

Platelet distribution width

16.2 (8.4–23.9)

16.5 (9.6–19.1)

0.183

Mean corpuscular hemoglobin

28.5 (14.5–36.9)

29 (20.9–32.7)

0.105

9 (6.1–14.5)

8.9 (5.4–12.7)

0.773

Mean platelet volume Mean corpuscular volume

84.6 (56–108)

84.9 (66–93)

0.775

0.58 (0.13–3.66)

0.49 (0.19–3.48)

0.019

1.86 (0.1–55)

2.26 (0.3–35.2)

0.363

Neutrophil to lymphocyte ratio

5.6 (0.15–41.2)

5.8 (1.7–30.8)

0.486

platelet to lymphocyte ratio

155 (22–1065)

150 (66–955)

0.712

Platelet to neutrophil ratio

25.4 (7.1–382)

25.3 (7.1–100)

0.851

White blood cell to lymphocyte ratio

7.1(1.15–46.7)

7.5 (1.1–32.2)

0.430

white blood cell to neutrophil ratio

1.3 (0.5–14.2)

1.2 (0.5–6.9)

0.204

Appendix lenght (mm)

60 (10–120)

60 (30–130)

0.581

Appendix width (mm)

10 (5–60)

10 (4–30)

0.734

n (%)

Total bilirubin C-reactive protein

Ultrasonography

Acute appendicitis (-)

137 (39)

24 (58.5)

Acute appendicitis (+)

214 (61)

17 (41.5)

Appendectomy type

Open

295 (77)

46 (95.8)

Lap

88 (23)

2 (4.2)

Histopathological findings

Appendix vermiformis

Acute appendicitis

237

Perforated acute appendicitis

Lymphoid hyperplasia

Carcinoid

Mucocele

Granulomatous appendicitis

Fibrous obliteration

E. Vermiculairs

Appendiceal perforation

Yes

40 (10.5)

2 (4.2)

343 (89.5)

46 (95.8)

Acute appendicitis

Yes

283 (74)

38 (79.2)

100 (26)

10 (20.8)

558

0.016

0.001

0.580

0.204

0.429

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Koรง et al. Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy

Table 2. Comparison of the ultrasonographic assessment of pregnant and non-pregnant patients

Pregnant (n=41)

Non- pregnant (n=351)

Acute appendicitis (+)

Acute appendicitis (-)

Acute appendicitis (+)

Acute appendicitis (-)

Ultrasonography acute appendicitis (+)

177

Ultrasonography acute appendicitis (-)

Sensitivity

50.0%

67.3%

Specificity 100% 57.9% Positive predictive value

100%

82.7%

Negative predictive value

29.2%

37.2%

Accuracy 58.5% 65.0%

Table 3. Literature review of some studies published in English language literature on ratio of the pregnant acute appendicitis References Journal

Total delivery or pregnancy

Pregnant appendicitis

Pregnant appendicitis/ Delivery (1000)

Aras

Rev Assoc Med Bras (1992). 2016;62:622-7

6.540

5.81

Masood

Obstet Gynecol Int J 2016;5: 00173

12.687

134

10.56

Aggenbach

Int J Surg. 2015;15:84-9

25.443

0.83

Cheng

Surg Endosc. 2015;29:1394-9

1.147.214

859

0.75

Kumamoto

Surg Today. 2015;45:1521-6

Abbasi

BJOG. 2014;121:1509-14

Al- Dahamsh Jung

13.479

2.45

7.037.386

7114

1.01

J College of Med Sci-Nepal 2012; 8: 36-43

9.783

2.86

J Korean Soc Coloproctol 2012;28:152-9

14.203

1.76

Agholor

J Obstet Gynaecol Res. 2011;37:1540-8

16.173

1.42

Park

Eur J Obstet Gynecol Reprod Biol. 2010 ;148:44

954

8.39

Freeland

Am J Surg. 2009;198:753-8

65.000

0.35

Kazim

Int J Surg. 2009;7:365-7

43.134

0.86

Machado

JSLS. 2009;13:384-90

16.803

1.55

Zhang

Chin Med J (Engl). 2009;122:521-4

30.098

102

3.39

Al-Mulhim

Saudi J Gastroenterol. 2008;14:114-7

67.990

0.96

Moreno-Sanz

J Am Coll Surg. 2007;205:37-42

3.969

2.27

Rollins

Surg Endosc. 2004;18:237-41

18.590

1.61

Ueberrueck

World J Surg. 2004;28:508-11

46.969

2.00

Raja

Rawal Med J 2003;28:52-5

3.812

2.89

Eryilmaz

Dig Surg 2002;19:40-4

31.480

0.76

Popkin

Am J Surg 2002; 183: 20-2.

36.000

0.64

Duqoum

East Mediterr Health J. 2001;7:642-5

16.443

0.61

De Perrot

Surg Laparosc Endosc Percutan Tech.2000;10:368

3.702

2.43

Hoshino

Int J Gynaecol Obstet. 2000;69:271-3

15.000

1.00

Mourad

Am J Obstet Gynecol. 2000;182:1027-9

66.993

1.00

Tracey

Am Surg. 2000;66:555-9

44.845

0.49

Affleck

Am J Surg. 1999;178:523-9

32.818

1.22

Al-Qudah

J Obstet Gynaecol. 1999;19:362-4

52.108

0.88

Andersen

Acta Obstet Gynecol Scand. 1999;78:758-62

32.163

1.74

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

559

KoĂ§ et al. Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy

Table 3. Literature review of some studies published in English language literature on ratio of the pregnant acute appendicitis (continued) References Journal

Total delivery or pregnancy

Pregnant appendicitis

Pregnant appendicitis/ Delivery (1000)

Hee

Int J Gynaecol Obstet. 1999;65:129-35

320.949

117

0.36

Wittich

Mil Med. 1999;164:671-4

6.050

0.99

Al-Mulhim

Int Surg. 1996;81:295-7

31.950

1.63

Aust N Z J Surg. 1995;65:799-803

38.070

1.00

Lopez

J Obstetrics Gynecol 1994; 14: 133-7

41.206

1.50

Halvorsen

Eur J Surg. 1992;158:603-6.

44.577

0.36

Mahmoodian

South Med J. 1992;85:19-24

12.349

0.73

Al-Qasabi

Ann Saudi Med. 1991;11:58-61

31.245

1.47

Mazze

Obstet Gynecol. 1991;77:835-40

720.000

778

1.08

Tamir

Am J Surg. 1990;160:571-5

73.000

1.15

Bailey

Am Surg. 1986;52(4):218-21

100.145

0.41

Horowitz

Arch Surg. 1985;120:1362-7

66.351

0.18

Weingold

Clin Obstet Gynecol. 1983;26:801-9

19.187

1.25

Farquharson

Scott Med J. 1980;25:36-8

50.089

0.50

Punnonen

Acta Chir Scand. 1979;145:555-8

20.363

1.18

Gomez

Am J Surg. 1979;137:180-3

76.580

0.46

Babaknia

Obstet Gynecol. 1977;50:40-4

25.847

0.46

Zaitoon

Am Surg. 1977;43:395-8

11.844

0.93

Cunningham

Obstet Gynecol. 1975;45:415-20

91.800

0.37

Mohammed

Can Med Assoc J. 1975;112:1187-8

34.270

0.73

Finch

Br J Surg. 1974;61:129-32

94.000

0.80

Taylor

N Z J Obstet Gynaecol. 1972;12:202-3

38.719

1.42

Oâ&#x20AC;&#x2122;Neill

Aust N Z J Obstet Gynaecol. 1969;9:94-9

91.500

0.68

Kurtz

Obstet Gynecol 1964; 23(4):528-532

84.260

0.49

Sarason

Obstet Gynecol. 1963;22:382-6

11.000

1.27

Bronstein

Am J Obstet Gynecol. 1963;86:514-6

39.000

0.51

King

Calif Med. 1962;97:158-62

74.000

0.49

Lee

JAMA. 1965;193:966-8

16.100

2.11

MacBeth

Can J Surg. 1961;4:419-28

59.758

0.84

Townsend

Am Surg. 1960;26:425-7

33.000

0.88

West

Am Surg. 1960;26:425-7

39.867

0.88

Sprong

Calif Med. 1959;91:258-60

19.932

1.00

Easton

Postgrad Med J. 1957;33:272-7

8.608

1.63

Hoffman

Am J Obstet Gynecol. 1954;67:1338-50

44.242

126

2.85

Meharg

Obstet Gynecol. 1953;1:460-5

6.106

4.09

Priddle

Am J Obstet Gynecol. 1951;62:150-5

59.403

0.86

Hamlin

N Engl J Med. 1950;244:128-31

92.772

0.43

Baer

JAMA. 1932;98:1359-64

16.543

1.69

Total 11.543.752

the study we present (26.0 vs. 20.8%). These results point out that higher NA rates demonstrate easier made surgical treatment decisions of surgeons to avoid AAp related com560

11.198

0.97

plications, such as perforation, whereas lower NA rates of pregnants demonstrate meticulously made surgical treatment decisions of surgeons or use diagnostic tools more often. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Koç et al. Comparison of the demographic and clinical features of pregnant and non-pregnant patients undergoing appendectomy

One of the subjects that AAp studies touch upon is the frequency of perforated AAp. This condition is the most important subject to be mentioned in these studies when its complications are considered. Some authors justify the relative favor between NA and complicated AAp, considering maternal and fetal complications and promote surgical treatment in all pregnants with a possibility of AAp.[20] Opponent authors emphasize the 4% rate of maternal and fetal complications among pregnants who underwent NA and be in relief against considering NA as an innocent procedure.[20,21] According to the literature analysis mentioned above, perforated AAp rates vary from 0% to 40.4% in pregnants and 3.7% to 29% in non-pregnants. Perforated AAp rate was high among pregnants in seven of these studies and was high among non-pregnants in three of these studies. These results reveal relatively high rates of both NA and perforated AAP among pregnants. In our study none of the pregnants that underwent NA experienced neither maternal nor fetal complication. On the contrary, one of the pregnants with a perforated AAP had an uncomplicated preterm delivery. Many studies compare histopathologically proven AAp and non-AAP patient groups (control groups) to reveal sensitivity, specificity and cut-off levels of biochemical laboratory parameters (WBC, MPV, RDW, PDW, Platelets, Neutrophil, CRP, Bilirubin) in diagnosis and predicting of AAp related complications.[22,23] Similar parameters are analyzed in pregnant AAp studies as well.[24] However, a limited number of studies comparing pregnant and non-pregnant AAp patients analyse WBC and neutrophil counts, some of which reveal higher WBC or neutrophil counts in pregnant AAp group and some of them have non-significant difference.[4,1,11–15] One of the most important features of the study presented is comparing the groups concerning all the parameters mentioned above and revealing an insignificant difference between the groups except the total bilirubin levels. Bilirubin is one of the most analyzed parameters in studies about AAp. Bacteria’s hepatic involvement via portal vein following proliferation inside appendix lumen leading to the limitation in hepatic uptake and excretion and cytokine-mediated inhibition of bile salt transport have been shown previously. [24–28] Besides, hemolysis related to systemic infection has also been shown to result in an increase of bilirubin load. Many studies show a relatively higher increase in total bilirubin levels in complicated and uncomplicated AAp cases when compared with NA and the highest increase in complicated AAp. [24–28] However, some studies report a relatively increased bilirubin level among AAp group without any significant difference between complicated and non-complicated AAp groups. [28] Bilirubin level has also been shown to be predicting factor for perforation and other complications related to AAp. To our knowledge, none of the pregnant AAp studies analyzed the relation between bilirubin level and AAp. This study reveals relatively higher levels of bilirubin in the non-pregnant AAp group compared with the pregnant AAp group. Besides, Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

the comparison of histologically-proven AAp cases revealed relatively higher bilirubin levels in the non-pregnant group. Currently, we have no comment to clarify relatively lower bilirubin levels in the pregnant group and this study requires to be supported with further prospective studies. We would like to share some exceptional facts of this study. First of all, non-pregnant appendectomised female patients in reproductive age were completely included in the control group to minimize the risk of bias. Secondly, the relatively lower sensitivity of US examination depends on the radiology residents on night-shift who are relatively less experienced. The third fact is the absence of an MR examination on any of the pregnants, as the MR examination and a radiology specialist were unavailable during night-shifts. The fourth is the difficulty in providing all of the patients’ Alvarado scores admitted in the emergency unit of our institution despite most of the patients with a preliminary AAp diagnosis are followed with this score. As a result, AAp is among the most frequent conditions requiring surgical treatment during pregnancy. Physiological changes of pregnants may interfere with clinical findings and biochemical parameters which leads to higher rates of perforated AAp among pregnant AAp patients. All patients with a preliminary diagnosis of AAp must be followed closely and evaluated with consecutive US examinations to minimize maternal and fetal complications. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.A.; Design: S.A., C.K.; Supervision: S.A., S.Y.; Fundings: C.K., B.S.; Materials: C.K., B.S., E.İ.C.; Data: C.K., B.S., E.İ.C.; Analysis: S.A.; Literature search: S.A., C.K.; Writing: S.A.; Critical revision: S.A., C.K., S.Y. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Apendektomi yapılan gebe ve gebe olmayan hastaların demografik ve klinik özelliklerinin karşılaştırılması Dr. Cemalettin Koç,1 Dr. Sami Akbulut,1 Dr. Ebru İnci Coşkun,2 Dr. Barış Sarıcı,1 Dr. Sezai Yılmaz1 1 2

İnönü Üniversitesi Tıp Fakültesi, Cerrahi ve Karaciğer Nakli Enstitüsü, Malatya İnönü Üniversitesi Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, Malatya

AMAÇ: Bu retrospektif çalışma akut apandisit ön tanısıyla apendektomi yapılan gebe ve gebe olmayan hastaların demografik ve klinikopatolojik özelliklerini karşılaştırmayı amaçlamaktadır. GEREÇ VE YÖNTEM: Haziran 2009 ve Ocak 2019 tarihleri arasında üreme çağındaki 431 kadın hastaya akut apandisit ön tanısıyla apendektomi yapıldı. Hastalar gebelik durumları gözönünde bulundurularak iki gruba ayrıldı: Gebe grup (n=48) ve gebe olmayan grup (n=383). Her iki grup demografik, klinik ve histopatolojik özellikler yönünden karşılaştırıldı. BULGULAR: Gebe ve gebe olmayan gruplar arasında total bilirubin (p=0.019) ve ultrasonografik bulgular (p=0.016) dışında istatistiksel olarak anlamlı farklılık saptanmadı. Gebe olmayan grupta negatif apendektomi ve perforasyon oranları sırasıyla %26 ve %10.5 olarak hesaplanırken gebe grupta bu oranlar sırasıyla %20.8 ve %4.2 olarak hesaplandı. Ultrasonografinin gebe grubundaki sensistivite, spesifisite ve doğruluk oranları sırasıyla %50, %100 ve %58.5 olarak saptanırken gebe olmayan grupta bu oranlar sırasıyla %67.3, %57.9 ve %65 olarak bulundu. Gebelerin %52.1’i birinci trimesterda, %29.2’si ikinci trimesterda ve geriye kalan %16.7’si üçüncü trimesterdaydı. Miadında gerçekleşen doğumların (%87.5) hiçbirinde fetal veya maternal komplikasyon gelişmedi. Buna karşın preterm gerçekleşen doğumların (%12.5) ikisi neonatal mortalite ile sonuçlandı. TARTIŞMA: İstatistiksel olarak anlamlılık göstermemekle birlikte gebelerde negatif apendektomi ve perfore akut apandisit oranları gebe olmayan hastalara göre daha düşük bulundu ki bu durumun en önemli sebebi akut karın ile başvuran gebelerin klinik olarak daha hassas bir şekilde değerlendirilmesidir. Anahtar sözcükler: Akut apandisit; apendektomi; gebelik; obstetrik Komplikasyonlar; preterm eylem. Ulus Travma Acil Cerrahi Derg 2020;26(4):555-562

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doi: 10.14744/tjtes.2020.12544

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ORIGIN A L A R T IC L E

An investigation into the effects of hemodynamic changes on the patient’s clinical condition during the treatment of patients undergoing aneurysmal subarachnoid hemorrhage Nihan Yaman Mammadov, M.D.,1 Achmet Ali, M.D.,2 Orkhan Mammadov, M.D.,3 Ararso Kedir Jima, M.D.,3 Günseli Orhun, M.D.,2 İbrahim Özkan Akıncı, M.D.4 1

Department of Anesthesiology, University of Health Sciences, Van Training and Research Hospital, Van-Turkey

Department of Anesthesiology, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

Department of Intensive Care Unit, Altunizade Acıbadem Hospital, İstanbul-Turkey

Department of Intensive Care Unit, Taksim Acıbadem Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: In this study, we investigated the hemodynamic changes in patients with aneurysmal subarachnoid hemorrhage (aSAH) during the intensive care unit and the effects of PiCCO on the hemodynamic clinical course during hydration and hypertension treatment. METHODS: In our study, 15 adult aSAH patients, whose aneurysm had been treated by surgery or coiling, were examined for the signs of vasospasm in between the dates 03/01/2015 and 01/03/2016. The PICCO measurement was made at least twice in a day. Positive daily fluid balance was attempted to be at least 1000 mL and the value of the Global end-diastolic index (GEDI) was targeted to 680 to 800 mL/m2 for each patient. The values of mean arterial pressure (MAP), systolic arterial pressure (SAP), heart rate (HR), central venous pressure (CVP), and cardiac index (CI), GEDI, systemic vascular resistance index (SVRI), extravascular lung water index (ELWI) measured by PiCCO, and daily neurological outcome of patients and GCS values were recorded. RESULTS: It had been observed that CVP value was randomly changing during the volume therapy, but the GEDI value determined by thermodilution was consistent. A positive correlation was detected between the period of reaching the hospital and the first measured value of SVRI. Low GEDI value was detected as a risk factor in the perspective of vasospasm, but an ideal GEDI value could not be determined. CONCLUSION: GEDI values were correlated with daily fluid balance. While low GEDI value was found as a risk factor, we could not determine an ideal GEDI value. Keywords: Fluid therapy; PiCCO; subarachnoid hemorrhage; vasospasm.

INTRODUCTION The most common complication of aneurysmal subarachnoid hemorrhage (aSAH) concerning mortality and morbidity is the development of delayed cerebral ischemia (DCI) due to cerebral vasospasm. Cerebral vasospasm is reported to be observed in 16–71% according to its definition.[1,2] The main

cause of mortality and morbidity associated with ischemic deficits, such as changes in consciousness and motor neurological losses, is defined as clinical vasospasm and occurs only in 17–21% of all aSAH patients.[1,3] Although prophylactic triple-H therapy (hypervolemia, hypertension, hemodilution) for preventing delayed cere-

Cite this article as: Yaman Mammadov N, Ali A, Mammadov O, Jima AK, Orhun G, Akıncı İÖ. An investigation into the effects of hemodynamic changes on the patient’s clinical condition during the treatment of patients undergoing aneurysmal subarachnoid hemorrhage. Ulus Travma Acil Cerrahi Derg 2020;26:563-567. Address for correspondence: Nihan Yaman Mammadov, M.D. Sağlık Bilimleri Üniversitesi Van Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Van, Turkey Tel: +90 444 99 65 E-mail: nihanyaman87@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):563-567 DOI: 10.14744/tjtes.2020.24412 Submitted: 29.09.2019 Accepted: 14.01.2020 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Yaman Mammadov et al. An investigation into the effects of hemodynamic changes on the patient’s clinical condition during the treatment of patients undergoing aSAH

bral ischemia was acceptable, current evidence does not support its efficacy and recommends maintaining normovolemia.[4] Induced hypertension and volume status have been regarded as important, but heart failure and pulmonary edema are the most important complications of this therapy.[5,6] Although blood pressure is a treatment goal for cerebral perfusion, monitoring cardiac output (CO) and stroke volume variation (SVV) are important for adequate treatment.[7] PiCCO, which is the transpulmonary thermodilution method, enables assessment of the patient’s hemodynamic status to guide fluid or vasoactive drug therapy. In recent years, it has been shown that the usage of PiCCO may be useful in the follow-up of SAH patients.[8] In this study, we aimed to evaluate physiological monitoring values for PiCCO in aSAH patients during hydration and hypertension (2H) treatment for the continuation of euvolemia.

Table 1. Demographic and descriptive characteristics Gender (male/female)

9/6

Age (year)

47.9±10.2

Height 166.0±10.3 Weight 80.1±9.2 Location of aneurysm

Anterior communicant artery

Posterior communicant artery

Middle cerebral artery

Carotid artery

GCS on admission

12.5±2.1

WFNS (I/II/III/IV/V)

1/5/5/3/1

Hunt and Hess score (I /II/III/IV)

0/5/8/2

Fisher score (I/II/III/IV)

0/5/6/4

Hospital admission day

2.6±1.7

GCS: Glasgow Coma Score; WFNS: World Federation of Neurosurgeons Score.

MATERIALS AND METHODS In this study, we included 15 adults, aSAH patients with aneurysm who were undergone to surgical clips or angiographic coils that were hospitalized between 01.03.2015 and 01.03.2016. Patients who did not want to participate in this study and who did not apply to our hospital despite the development of aSAH on the first three days and the patients who were admitted to our Intensive Care Unit with a poor neurological score of age <18 [World Federation of Neurosurgeons Score (WFNS): 5 and low Glasgow Coma Score (GCS) <4], incidental aneurysms and patients whose aneurysm could not be closed by surgical or endovascular methods were excluded from this study. A femoral PiCCO artery catheter and a subclavian CVP catheter were inserted to the patients, and PiCCO measurement was performed at least twice a day, morning and evening. The insensible fluid losses of the patients were considered to be 400–600 mL and the daily fluid balance was planned to be approximately 1000 mL positivity to achieve isovolemia and the global end-diastolic index (GEDI) value measured by PiCCO was targeted to be the normal range of 680– 800 mL/m2. Mean arterial pressure (MAP), systolic arterial pressure (SAP), heart rate (HR), central venous pressure (CVP) and cardiac index (CI), GEDI, systemic vascular resistance index (SVRI), extravascular lung water index (ELWI) measured by PiCCO were recorded. In addition, patients’ Fisher score,[9] Hunt-Hess score,[10] and daily neurological examination results were recorded as GCS values. In addition, after additional fluid replacement and/or hemodynamic support, PiCCO measurements were repeated to evaluate the effects of CI, GEDI and/or SVV measurements on the improvement of clinical vasospasm findings. Intensive care and hospital stay, Glasgow outcome scores and morbidity were recorded. 564

Clinical vasospasm findings: Minor findings; headache, agitation, leukocytosis (non-infectious), unconsciousness and disorientation; major findings were; decrease in GCS (>2), new motor deficit and/or aphasia and/or dysphasia were accepted as newly developing visual defects. Quantitative data were expressed as mean and standard deviation, and qualitative data were expressed as number and percentage of cases. Pearson correlation analysis was used to correlate the quantitative data. Correlation levels were defined as r≤0.3 low, 0.3<r<0.5 medium and r≥0.5 advanced. SPSS 15.0 program was used for statistical analysis of data and graphs.

RESULTS In total, 15 patients completed this study (Fig. 1). The distribution of the aneurysm concerning location is shown in Table 1. The average GCS mean of patients was 12.5±2.1 days and on hospitalization day after bleeding average was 2.6±1.7 days (Table 1). It was observed that CI values were statistically higher on the 4th day, 6th day, 8th day, 10th day, 12th day than the first days (Fig. 2). In the follow-up of the fluid treatment

25 patients has been evaluated Excluded patients • Patients under 18 years of age (n=2) • Patients who refused to participate in the study (n=2) • Patients jith inaccurate or missing data (n=6) 25 patients completed the study

Figure 1. Working flow chart.

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during intensive care follow-ups, it was observed that CVP values were not appropriate and CVP values were changed inappropriately and randomly during the treatment process However, GEDI value determined by thermodilution showed a consistent course with the fluid amount given and daily balance of the patient (Figs. 3, 4). In addition, it was figured out that the data measured by thermodilution were more objective than central venous pressure in the management of fluid therapy. Significant correlation between hospitalization time and the first measured SVRI value was observed (Fig. 5). This correlation was thought to be related to the attempt to achieve cardiac output by increasing systemic vascular resistance in SAH patients who did not receive adequate fluid therapy. Low GEDI was found to be a risk factor for vasospasm development (Fig. 6).

Cardiac Index (CI) L/min/m2

5.50 5.00 4.50 4.00 4.55

3.50 3.93

3.00 2.50

3.48

4.69 3.92

900.00 900.00 900.00 860

845

829

812

900.00

781

759

781

716

900.00

Day 2 Day 4 Day 6 Day 8 Day 10 Day 12

Out

Figure 4. Global end diastolic index (GEDI) data. 2.900.00

4.20

3.68

900.00

Sistemic Vascular Resistance Index (SVRI)

In our study, no ideal GEDI value could be determined although there was a negative correlation between the number of days with vasospasm symptoms and the GEDI value.

Global End - Diastolic Index (GEDI) mL/m2

Yaman Mammadov et al. An investigation into the effects of hemodynamic changes on the patientâ&#x20AC;&#x2122;s clinical condition during the treatment of patients undergoing aSAH

2.800.00 2.700.00 2.600.00 2.500.00 2.400.00 2.300.00 2.200.00 2.100.00

2.379 2.284

2.000.00

2.243 2.142

1.900.00 1.800.00

3.68

2.070

2.136

2.073

Day 2 Day 4 Day 6 Day 8 Day 10 Day 12

2.142

Out

Figure 5. Systemic vascular resistance index (SVRI) data. Day 2

Day 4

Day 6

Day 8 Day 10 Day 12

Out

900.00

Figure 2. Cardiac index data. Mean GEDI value

875.00

Central Venous Pressure (CVP)

13.00

11.00

850.00 825.00 800.00

9.00

775.00 7.00 4.00

5.00

3.00

8 6

CVP in CVP 1 CVP 2 CVP 3 CVP 4 CVP 5 CVP 6 CVP out

Figure 3. Mean values of central venous pressure measurements according to follow-up days.

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8.00

10.00

12.00

14.00

Vasospasm seen number of days

6.00

Figure 6. Number of days with vasospasm and mean global end diastolic index (GEDI) correlation curve.

DISCUSSION In our study, a high correlation was found between the first day of hospitalization and the first measured SVRI value after 565

Yaman Mammadov et al. An investigation into the effects of hemodynamic changes on the patient’s clinical condition during the treatment of patients undergoing aSAH

bleeding in aSAH patients, and low GEDI value was found to be a risk factor for the development of vasospasm. In addition, it was found that the data measured by thermodilution were more objective than CVP in the management of fluid therapy. In addition to neurological symptoms after aSAH, cardiac and pulmonary effects are seen as a result of sympathetic activation and parasympathetic dysfunction due to secreted neuromediators after injury.[11,12] Following the clinical development of SAH, in patients, increased reflex sympathetic stimulation with QT prolongation in ECG and arrhythmias were seen; concerning hemodynamic, as observed in our study, to ensure cerebral perfusion, hypertension was detected; and decrease in CI and increase in SVRI is also observed.[13,14] Studies have shown that there is a correlation between the severity of bleeding and cardiac complications and that cardiac dysfunction is respectively more serious after severe bleeding.[15] Although there are negative studies regarding the effectiveness of 2H all over the world, in some centers, this method (2H) is used in the treatment of vasospasm after SAH.[16–18] Hypertension and hypervolemia are the two treatments responding to 2H. To overcome the vasospasm after aSAH, while maintaining the intravascular volume, it is necessary to increase CI and simultaneously increase cerebral blood flow. This is the basic physiological logic of 2H treatment in aSAH treatment. In a randomized study of 82 patients with SAH, Lennihan et al. [16] showed that the risk of hypotension during intensive care treatment was lower in the group of patients who underwent hypervolemia and consequently, DCI was observed less. Mortality and morbidity were better in the hypervolemia group, although there was no statistical difference. However, in recent studies, a positive fluid balance was found to be associated with poor outcomes in patients diagnosed with aSAH,[19] and prophylactic hypervolemia was not found to reduce the risk of late cerebral ischemia,[16] the fluid limitation has been experienced to be harmful.[19,20] In the method of our study, we took the patient’s involuntary losses (Perspiratio Insensibilis) as the physiological value of 450–500 mL, and we gave another 500 mL of fluid to compensate for the additional losses that arise from samples taken for laboratory tests, lumbar puncture and fever. Furthermore, we aimed to keep the volume balance close to the upper limits of isovolemia by avoiding involuntary hypovolemia with an average of 100 mL positive fluid balance. With this fluid treatment approach, we achieved our goal in all patients, as demonstrated by the results of PiCCO measurements. Studies have shown that PiCCO-administered fluid therapy would be more appropriate for the treatment of vasospasm.[8] According to Mutoh et al.,[7] the value of the GEDI measured by thermodilution method was described the volume status of patients significantly higher sensitivity and specificity compared to CVP value and in the PiCCO group of patients, vasospasm symptoms and DCI were determined less frequently compared to the traditional follow-up group. In addition, it was figured out that pulmonary complications were less experienced in the PiCCO group. In this study, we kept track of aSAH patients with the data obtained using thermodilution method. In the fluid treatment during intensive care 566

follow-up, we found that the CVP value was inappropriate and the CVP values changed during the treatment period in an inappropriate and random manner. The GEDI value determined by thermodilution was consistent with the amount of fluid administered and the daily balance of the patient. Similar to our study, other studies in the literature recommend the use of hemodynamic parameters obtained from thermodilution measurements performed with PiCCO to optimize fluid balance and prevent pulmonary complications in the follow-up of aSAH patients.[7,8,14] In our study, we also found that in patients with increased volume equilibrium with fluid therapy, the measured SVRI value decreased over time. Although previous studies have shown that low CI and GEDI values have negative effects on mortality and morbidity, no ideal GEDI value to be recommended in patient follow-up has been defined.[5,14,21] The GEDI value (normal range 680–800 mL/m2) was associated with both pulmonary edema (>921 mL/m2) and DCI (<822 mL/m2) in a study conducted in 2014.[5] In our study, we found a negative correlation between the number of days with vasospasm symptoms and GEDI value and found that low GEDI value was an important risk factor for the development of clinical vasospasm. However, as a result of our study, we could not reach the cut-off value of the SVRI and GEDI values in the treatment of vasospasm. The most important reason for this is that we have not reached the number of patients required to reach this result, which is the most important limitation of our study.

Conclusion The results of the present study show that PiCCO-guided hemodynamic management helps to optimize fluid input and balance without negatively impacting on preload parameters and GCS. However, we need multicentre studies with large patient groups to obtain more accurate results. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: N.Y.M., İ.Ö.A.; Design: N.Y.M., İ.Ö.A.; Supervision: A.A., İ.Ö.A. Fundings: N.Y.M., İ.Ö.A.; Materials: O.M., A.K.J., G.O.; Data: O.M., A.K.J., G.O.; Analysis: A.A., G.O., O.M.; Literature search: N.Y.M., İ.Ö.A.; Writing: N.Y.M., O.M., İ.Ö.A.; Critical revision: O.M., İ.Ö.A., N.Y.M. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, et al. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke 2009;40:1963−8. 2. Dupont SA, Wijdicks EF, Manno EM, Lanzino G, Rabinstein AA. Predic-

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Yaman Mammadov et al. An investigation into the effects of hemodynamic changes on the patient’s clinical condition during the treatment of patients undergoing aSAH tion of angiographic vasospasm after aneurysmal subarachnoid hemorrhage: value of the Hijdra sum scoring system. Neurocrit Care 2009;11:172–6. 3. Frontera JA, Claassen J, Schmidt JM, Wartenberg KE, Temes R, Connolly ES Jr, et al. Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified fisher scale. Neurosurgery 2006;59:21-7. 4. Kurtz P, Helbok R, Ko SB, Claassen J, Schmidt JM, Fernandez L, et al. Fluid responsiveness and brain tissue oxygen augmentation after subarachnoid hemorrhage. Neurocrit Care 2014;20:247−54. 5. Tagami T, Kuwamoto K, Watanabe A, Unemoto K, Yokobori S, Matsumoto G, et al; SAH PiCCO Study Group. Optimal range of global end-diastolic volume for fluid management after aneurysmal subarachnoid hemorrhage: a multicenter prospective cohort study. Crit Care Med 2014;42:1348−56. 6. Gonzalez J, Delafosse C, Fartoukh M, Capderou A, Straus C, Zelter M, et al. Comparison of bedside measurement of cardiac output with the thermodilution method and the Fick method in mechanically ventilated patients. Crit Care 2003;7:171−8. 7. Mutoh T, Kazumata K, Ishikawa T, Terasaka S. Performance of bedside transpulmonary thermodilution monitoring for goal-directed hemodynamic management after subarachnoid hemorrhage. Stroke 2009;40:2368–74. 8. Bajorat J, Hofmockel R, Vagts DA, Janda M, Pohl B, Beck C, et al. Comparison of invasive and less-invasive techniques of cardiac output measurement under different haemodynamic conditions in a pig model. Eur J Anaesthesiol 2006;23:23−30. 9. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6:1–9. 10. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968;28:14–20. 11. Jeon IC, Chang CH, Choi BY, Kim MS, Kim SW, Kim SH. Cardiac troponin I elevation in patients with aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc 2009;46:99–102. 12. Naidech AM, Kreiter KT, Janjua N, Ostapkovich ND, Parra A, Com-

michau C,et al. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation 2005;112:2851−6. 13. van der Bilt IA, Hasan D, Vandertop WP, Wilde AA, Algra A, Visser FC, et al. Impact of cardiac complications on outcome after aneurysmal subarachnoid hemorrhage: a meta-analysis. Neurology 2009;72:635−42. 14. Yoneda H, Nakamura T, Shirao S, Tanaka N, Ishihara H, Suehiro E, et al; SAH PiCCO Study Group. Multicenter prospective cohort study on volume management after subarachnoid hemorrhage: hemodynamic changes according to severity of subarachnoid hemorrhage and cerebral vasospasm. Stroke 2013;44:2155−61. 15. Mashaly HA, Provencio JJ. Inflammation as a link between brain injury and heart damage: the model of subarachnoid hemorrhage. Cleve Clin J Med 2008;75:S26–30. 16. Lennihan L, Mayer SA, Fink ME, Beckford A, Paik MC, Zhang H, et al. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial. Stroke 2000;31:383−91. 17. Keller TS, McGillicuddy JE, LaBond VA, Kindt GW. Modification of focal cerebral ischemia by cardiac output augmentation. J Surg Res 1985;39:420–32. 18. Egge A, Waterloo K, Sjøholm H, Solberg T, Ingebrigtsen T, Romner B. Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study. Neurosurgery 2001;49:593–606. 19. Kissoon NR, Mandrekar JN, Fugate JE, Lanzino G, Wijdicks EFM, Rabinstein AA. Positive fluid balance is associated with poor outcomes in subarachnoid hemorrhage. J Stroke & Cerebrovascular Diseases 2015;24:2245−51. 20. Rosenwasser RH, Delgado TE, Buchheit WA, Freed MH. Control of hypertension and prophylaxis against vasospasm in cases of subarachnoid hemorrhage: a preliminary report. Neurosurgery 1983;12:658–61. 21. Taccone FS, Citerio G; Participants in the International Multi-disciplinary Consensus Conference on Multimodality Monitoring. Advanced monitoring of systemic hemodynamics in critically ill patients with acute brain injury. Neurocrit Care 2014;21:S38–63.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Anevrizmal subaraknoid kanama geçiren hastalarda tedavi süresince gelişen hemodinamik değişikliklerin kliniğe etkilerinin araştırılması Dr. Nihan Yaman Mammadov,1 Dr. Achmet Ali,2 Dr. Orkhan Mammadov,3 Dr. Ararso Kedir Jima,3 Dr. Günseli Orhun,2 Dr. İbrahim Özkan Akıncı4 Sağlık Bilimleri Üniversitesi Van Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Van İstanbul Üniversitesi İstanbul Tıp Fakültesi, Anesteziyoloji Anabilim Dalı, İstanbul 3 Altunizade Acıbadem Hastanesi, Genel Yoğun Bakım Kliniği, İstanbul 4 Taksim Acıbadem Hastanesi, Genel Yoğun Bakım Kliniği, İstanbul 1 2

AMAÇ: Çalışmamızda anevrizmal subaraknoid kanama (aSAK) hastalarının yoğun bakım izlemlerinde hemodinamik değişiklikleri ve hidrasyon, hipertansiyon tedavisi sırasında PiCCO ile ölçülen hemodinamik parametrelerin klinik seyre etkisini inceledik. GEREÇ VE YÖNTEM: Çalışmamızda 01.03.2015 ve 01.03.2016 tarihleri arasında cerrahi klip veya endovasküler koil ile anevrizması tedavi edilen, erişkin, 15 aSAK hastası vazospazm açısından incelendi. Günde en az iki kez PiCCO ölçümü yapıldı. Sıvı tedavisi günlük en az 1000 mL pozitiflik olacak şekilde, Global end-diyastolik İndeks (GEDİ) değeri 680–800 mL/m2 şeklinde hedeflendi. Hastaların geliş ortalama arter basıncı (OAB), sistolik arter basıncı (SAB), kalp atım hızı (KAH), santral venöz basınç (CVP) ve kardiyak indeks (CI), GEDI, sistemik vasküler rezistans indeksi (SVRI), ekstravasküler akciğer volüm indeksi (ELWI) değerleri kaydedildi. Hastaların günlük nörolojik muayeneleri, klinik vazospazm bulguları, GKS değerleri kaydedildi. BULGULAR: Hastaların volüm durumları ve volüm tedavisi takibinde CVP değerinin rastgele değiştiği fakat termodilüsyon ile saptanan GEDI değerinin uyumlu olduğu görüldü. Hastaneye geliş süresi ile ilk ölçülen SVRI değeri arasında ileri düzeyde pozitif korelasyon saptandı. Düşük GEDI değerinin vazospazm açısından risk faktörü olduğu bulundu. TARTIŞMA: Volüm tedavisinin takibindeki değişikliklerle GEDI değerindeki değişikliklerin uyumlu olduğu görüldü. Düşük GEDI değerinin vazospazm açısından risk faktörü olduğu bulunmasına rağmen, önerilecek ideal bir GEDI değeri saptanamadı. Anahtar sözcükler: PiCCO; sıvı tedavisi; subaraknoid kanama; vazospazm. Ulus Travma Acil Cerrahi Derg 2020;26(4):563-567

doi: 10.14744/tjtes.2020.24412

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ORIGIN A L A R T IC L E

Blood-aqueous barrier deterioration following retained metallic corneal foreign body: A laser flare photometric study İsmail Umut Onur, M.D., Ercan Çavuşoğlu, M.D.,

Sibel Zırtıloğlu, M.D., Ulviye Yiğit, M.D.

Ozan Sonbahar, M.D.,

Department of Ophthalmology, University of Health Sciences, İstanbul Bakirköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: This study aims to use laser flare photometry to evaluate flare changes in patients following corneal damage from a metallic foreign body (FB). METHODS: Foreign body injured eyes and the healthy fellow eyes of 54 consecutive patients were studied in this comparative, observational, cross-sectional study. Flare levels were analyzed according to demographics, history of previous exposures, foreign body location, and foreign body penetration into the injured cornea. RESULTS: The mean flare value was significantly higher for the eyes with corneal foreign body injury compared to the fellow-control eyes (11.35±14.17 ph/ms and 6.30±3.81 ph/ms, respectively) (p=0.014). The mean flare values were significantly lower in eyes with a history of more than one previous corneal foreign body removal flare values than in other eyes (p=0.029). CONCLUSION: Flare is increased by corneal foreign body exposure. However, eyes that experience multiple previous corneal foreign body exposures may show relatively low flare, probably due to corneal desensitization. Keywords: Anterior chamber reaction; corneal foreign body; laser flare photometry.

INTRODUCTION A non-penetrating but retained corneal foreign body (FB) is the most common, although inherently preventable, type of eye injury.[1] FB is a frequently occurring injury in construction and metal industry workers due to occupational accidents involving metallic FBs.[1] Corneal FBs may decrease the quality of vision by causing scars on the visual axis and by triggering secondary infections ranging from keratitis to endophthalmitis.[2] Under normal conditions, the anterior chamber of the eye is an optically empty space.[3] However, disruption of the bloodocular barriers leads to the leakage of serum proteins into

the anterior chamber.[3] Inflammation increases the amount of protein in the aqueous humor by promoting the deterioration of the blood-aqueous barrier (BAB),[4] and the amount of protein can be subjectively evaluated using slit-lamp biomicroscopy.[5] Clinical scores by slit-lamp biomicroscopy range from +1 to +4 according to the SUN classification system;[6] however, this is a subjective method and is highly dependent on the experience of the physician.[7] A better method may be laser flare photometry, an automated technique that quantifies the particulate matter and humoral water in the anterior chamber.[8] Laser flare photometry, in particular, allows the detection of subclinical alterations in the blood-ocular barrier and identifies subtle pathological changes that slitlamp biomicroscopy cannot detect.[9]

Cite this article as: Onur İU, Zırtıloğlu S, Sonbahar O, Çavuşoğlu E, Yiğit U. Blood-aqueous barrier deterioration following retained metallic corneal foreign body: A laser flare photometric study. Ulus Travma Acil Cerrahi Derg 2020;26:568-573. Address for correspondence: Sibel Zırtıloğlu, M.D. Sağlık Bilimleri Üniversitesi, İstanbul Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Göz Kliniği, İstanbul, Turkey Tel: +90 212 - 414 71 71 E-mail: sibel1077@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):568-573 DOI: 10.14744/tjtes.2019.88560 Submitted: 08.05.2019 Accepted: 15.12.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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A correlation between clinical scoring according to SUN classification system and quantitative readings by flare photometry for uveitic eyes has previously been documented. For example, Konstantopoulou et al.[9] evaluated eyes with uveitis by having experienced physicians independently grade eyes according to the SUN classification, while at the same time obtaining flare values with a flare meter to compare flare based scoring. Flare photometry studies have also been used for specific ophthalmologic disorders, including glaucoma and uveitis, as well as in postoperative and posttraumatic cases. [10] However, to our knowledge, no studies have yet evaluated the flare changes in eyes due to non-penetrating trauma with retained corneal FBs, although these injuries would be expected to generate subclinical and subtle changes in the flare detectable by flare meters. The present study aims to evaluate flare following the breakdown of the BAB induced by non-penetrating ocular injury with retained metallic corneal FBs, focusing on patient age, lesion size, the distance of the FB from the limbus, and FB penetration depth.

MATERIALS AND METHODS

Inc., Fort Worth, TX) until no residual rust staining was evident. The size of the corneal epithelial defect was measured in millimeters after the removal of the corneal FB. Topical antibiotic treatment (Ofloxacin four times a day and Tobramycin ointment two times a day) was prescribed after the FB removal. Seven measurements were recorded with the laser flare photometer (LFM, Kowa FM-700, Kowa Company Ltd., Tokyo, Japan) under a background scatter of <10% immediately after removal of the corneal FB. The lowest and highest readings were discarded, and the mean of the five remaining values was recorded according to the manufacturer’s guidelines. Measurements were deleted if they were selected by the machine’s error level setting as outliers. All patients were treated and assessed by the same examiner (O.S.). Measurements were performed in a darkened room. Exclusion criteria included any conditions that could affect the measurements of the KOWA FM-700 laser flare photometer, such as corneal scarring, residual rust rings, or incomplete foreign body removal at enrollment; a narrow anterior chamber; extensive posterior synechiae; mature cataract, hyphema, history of uveitis, vitreous hemorrhage, ocular surgery within the past three months, use of anti-glaucoma drugs, or non-inflammatory posterior segment disorders (i.e., diabetic retinopathy, retinal vein occlusion, retinitis pigmentosa, or choroidal melanoma).[8,12,13] No patients had infectious keratitis at the time of corneal FB removal.

Flare values are known to increase with age.[11] Therefore, our inclusion criteria limited the patient ages to between 20 and 40 years. Our evaluation included 54 injured eyes of 54 consecutive patients who were referred to our tertiary eye clinic for retained corneal FB removal during September 2017; the healthy fellow-eyes were evaluated as the control group. This study was approved by the institutional review board of the hospital in accordance with the tenets of the Declaration of Helsinki (2017/117). Informed consent was obtained from all individual participants in the study. This study was designed as a prospective, cross-sectional, observational study to compare the flare measurements of the affected versus the healthy fellow eyes.

Statistical Analysis

At presentation, the patients were examined for best-corrected visual acuity according to the standard decimal chart. Anterior and posterior segment examinations were performed, including measurement of intraocular pressure (IOP). Demographic data were collected, including patient age, occupation, and the number of previous referrals of the affected eye for FB removal. All measurements were conducted after pupil dilatation (1% tropicamide). The healthy control felloweyes were also evaluated clinically and by laser flare photometry. Other collected data included the referral time from the injury, the size of the corneal FB and its distance to the limbus, as well as the penetration site into the cornea (epithelium, superficial stroma, or deep stroma) as recorded by biomicroscopy examination.

RESULTS

The retained corneal FBs and rust were removed using a 25-gauge needle under local anesthesia provided by topical proparacaine hydrochloride (Alcaine 0.5%, Alcon Laboratories Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

All data were analyzed using IBM SPSS Statistics for Windows Version 21.0 (IBM Corp., Armonk, NY, US). Data were described as means and standard deviations (Mean±SD) and percentages. The distribution of the data was evaluated using the Kolmogorov-Smirnov test. The Mann-Whitney U and Kruskal-Wallis tests were used to analyze quantitative independent data. The Wilcoxon test was used to analyze the dependent quantitative data, and Spearman correlation analysis was used for correlation analysis. The effect level was assessed by univariate and multivariate logistic regression analysis. P-values less than 0.05 were considered statistically significant.

All 54 patients were male, and their mean age was 32.9±9.5 years. The patient age and anterior chamber flare values showed no significant correlation (p=0.450). The occupations of the patients were metal grinding (30.2%), construction (22.6%), and electrical installation (11.3%). No statistically significant difference was noted for flare measurements among the patients in their distinct occupational groups. All injuries resulted from high-velocity metallic FB spinning off from cutting and chopping machines the patients had been using. The mean flare value was significantly higher for the eyes 569

Onur et al. Blood-aqueous barrier deterioration following retained metallic corneal foreign body: A laser flare photometric study

Previous FB History None 1

.04

More than 1

.03 Previous FB History

Size of Corneal FB (mm)

.05

.02

.01

.00 .0

10.0

20.0 30.0 Flare (ph/ms)

40.0

50.0

Figure 1. Size of corneal foreign body and flare.

with corneal FB than for the fellow control eyes (11.35±14.17 vs. 6.30±3.81; p=0.014). The mean diameter of the largest corneal FBs was 0.27±0.21 (0.05–5.00) mm. A significant moderate correlation (r=0.320, p=0.021) was detected between the flare value and the size of the corneal FB (Fig. 1). Flare values according to the history of previous corneal FB removals are shown in Table 1. A statistically significant difference was noted between the mean flare values of the eyes with no previous removal, one previous removal, and multiple previous removals of corneal Table 1. Flare values in relation to the number of previous foreign body removals Number of previous n % corneal FB removals

ph/ms (Mean±SD)

None

21 52 13.4±17.2 0.024

9 23 14.6±14.6

10 25 5.5±2.2

FB: Foreign body; SD: Standard deviation.

5.0

10.0

15.0 20.0 25.0 Flare (ph/ms)

30.0

35.0

40.0

45.0

Figure 2. Flare and number of previous removals.

FBs (p=0.024). No significant difference was observed between the mean values of flare in the eyes with one previous removal and no previous removal of corneal FBs (p=0.375), whereas the value of the flare was significantly lower in eyes with multiple previous removals than in the other eyes (p=0.029) (Fig. 2). Notably, the age of the patients did not show any significant correlation with the number of prior corneal FB removals (p=0.330). The mean distance between the corneal FB and limbus was 2.97±1.55 (0.01–5.00) mm. No significant correlation was detected between the flare value and the limbal distance (p=0.793). Corneal FBs were located in the epithelium in 24.5% of the patients, in the superficial stroma in 60.4%, and in the deep stroma in 15.1%, respectively. No significant differences were found for the flare values among the eyes with deep stromal, superficial stromal, and epithelial corneal FB locations (p=0.089).

Table 2. Logistic regression analysis of parameters in differentiating between low and high flare values Flare (Low [<8 ph/ms] vs High [≥8 ph/ms])

Univariate model (CI 95%)

Multivariate model

Age

1.01 0.95–1.07 0.764

Number of FB removals (≤1 vs >1)

0.37

0.17–0.84

0.017

Depth of corneal penetration

0.87

0.42–1.82

0.718

0.39

(CI 95%)

0.17–0.87

Referral time

1.00

0.57–1.76

0.991

Distance of FB to limbus (mm)

0.73

0.47–1.14

0.166

Size of FB (mm)

36.7

1.4–960

0.031

58.4

1.5–2199

0.022

0.028

CI 95%: confidence interval 95%. OR: Odds ratio; FB: Foreign body; CI: Confidence interval.

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The corneal FB was removed within 12 hours in 15.1% of the patients, between 12 and 24 hours in 34%, between 24 and 48 hours in 32.1%, and after 48 hours in 18.9%. The differences in flare values according to the referral time were not statistically significant (p=0.705). Table 2 shows the logistic regression analysis. The high vs. low values for flare showed significant effects in both the univariate and multivariate models for the number of previous FB removals and the size of the FB (p<0.05).

DISCUSSION Non-penetrating ocular injury from a retained corneal FB is among the most common reasons for referrals to the emergency ophthalmology clinics in our country.[1] The male predominance in the patient demographics is related to the high proportion of injuries occurring in industrial work environments, as shown in this study. A retained metallic corneal FB is a common presentation at the ophthalmology emergency service and has the potential to cause ocular morbidity.[14,15] In the present study, we searched for the subtle inflammatory response evoked by the corneal FB and possible influencing factors. We found a significantly higher mean flare value in the eyes with the retained corneal FBs than in the healthy fellow eyes, and the flare level showed a moderate correlation with the size of the corneal FB. A statistically significant difference also existed between groups according to the previous history of corneal FB removal. The objectivity and reproducibility of laser flare photometry have been documented repeatedly,[16] as the relationship between the SUN classification system and laser flare photometry readings have been studied in numerous reports.[9,17] The clinical grading system for flare measurement was confirmed as quite subjective, whereas laser flare photometry allowed quantitative measurements and could discern even minute changes. Laser flare photometry values correlate well with the clinical flare grades based on slit-lamp examination; however, a wide range of laser flare photometry measurement values corresponding to specific clinical grades, with a notable overlap between grades.[18,19] In our study, the mean flare values induced by corneal FBs predominantly fell into the faint or moderate stages of flare, according to the SUN system. Changes in flare may actually indicate a significant alteration in disease activity or recovery of the blood-aqueous barrier. Laser flare photometric studies involve a broad range of clinical entities, from uveitis of all types to cataract surgery, corneal and refractive surgery, glaucoma, and retinal vascular disorders.[20] Lages et al.[21] reported 664 and 742 ph/ms values in two cases with endophthalmitis following intravitreal injection of anti-VEGF and proposed a cut of the level of >50 ph/ms on day 3 to promote evaluation for endophthalmitis. Mean flare values were reported in the 300–500 ph/ms range in several other uveitis studies, while 10–40 ph/ms peak values Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

were shown immediately after penetrating keratoplasty and corneal refractive procedures or in the acute phase of corneal graft rejection.[20,22] The flare values in our study appear particularly comparable to values reported in the keratoplasty and refractive studies mentioned above, which suggests that similar pathophysiological responses may be of concern. Damage to the epithelial integrity causes the release of some chemoattractants that attract polymorphonuclear leukocytes (PMNs) from the limbal vessels and tear film. PMNs then invade the stroma to engulf and eliminate debris.[23] Because the corneal FBs were mostly removed within 48 hours, as shown in our study, we considered that the flare in this scenario was likely to be relevant to the early phase of inflammation. However, Rosenbaum et al.[24] evaluated the correlation of ocular deformation with BAB breakdown and showed that inflammation flared up as the deformation intensified. Therefore, the moderate correlation between flare and the size of corneal FB determined in the present study might indeed be attributable to the impact force leading to ocular deformation, which was indirectly related to the size of the corneal FBs. In this study, eyes with a history of multiple previous corneal FB removals also had a significantly lower mean flare level than the other eyes, which requires an explanation. We cautiously attribute this finding to anterior chamber associated immune deviation (ACAID), which is a form of immune tolerance to alloantigens placed in the anterior chamber of the eye. ACAID downregulates the antigen-specific delayed-type hypersensitivity (DTH) response while promoting the production of non-complement fixing antibodies and humoral immunity.[25] This process is related to F4/80+antigen presenting cells (APC), which capture intraocular antigens, enter the bloodstream, and migrate to the marginal zone of the spleen, where their interactions with CD4+ T cells, γδT cells, B cells, and natural killer (NK) T cells result in the generation of two groups of antigen- specific regulatory T cells (Tregs): CD4+ CD25+ Tregs and CD8+ Tregs.[26] However, we can only speculate about the possibility of ACAID triggered by multiple exposures to metallic corneal FBs, given the scope of our study. To the best of our knowledge, no ophthalmic papers have mentioned this concept. In fact, following recurrent graft rejections characterized by DTH to donor alloantigens and leukocytic cellular infiltration of the graft site, the host becomes more sensitized, and the time to rejection decreases.[27,28] This study has some important limitations that should be recognized. One is that the evaluation of ocular inflammation was cross-sectional, for practical reasons. A longitudinal follow-up may display the course of inflammation in detail and may indicate the timing of the peak response or accelerated phase. A second limitation is that “metallic” is a general definition, and the variability in the exact chemical composition of the FB is highly likely to stimulate a variable inflammatory response. 571

Onur et al. Blood-aqueous barrier deterioration following retained metallic corneal foreign body: A laser flare photometric study

In conclusion, this preliminary descriptive flare photometry study revealed that subtle intraocular inflammation might be evoked by metallic corneal FB exposure and might show some degree of variability. Further studies with metallic or non–metallic FB exposures are required to confirm or disprove our findings and to verify the potential relevance to the clinical setting. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: İ.U.O.; Design: E.Ç.; Supervision: İ.U.O.; Fundings: O.S.; Materials: U.Y.; Data: O.S.; Analysis: İ.U.O., S.Z.; Literature search: İ.U.O., S.Z.; Writing: İ.U.O., S.Z.; Critical revision: İ.U.O. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Ozkurt ZG, Yuksel H, Saka G, Guclu H, Evsen S, Balsak S. Metallic corneal foreign bodies: an occupational health hazard. Arq Bras Oftalmol 2014;77:81–3. 2. Welch LS, Hunting KL, Mawudeku A. Injury surveillance in construction: eye injuries. Appl Occup Environ Hyg 2001;16:755–62. 3. Tugal-Tutkun I, Herbort CP. Laser flare photometry: a noninvasive, objective, and quantitative method to measure intraocular inflammation. Int Ophthalmol 2010;30:453–64. 4. Freddo TF. A contemporary concept of the blood-aqueous barrier. Prog Retin Eye Res 2013;32:181–95. 5. Martin R. Cornea and anterior eye assessment with slit lamp biomicroscopy, specular microscopy, confocal microscopy, and ultrasound biomicroscopy. Indian J Ophthalmol 2018;66:195–201. 6. Trusko B, Thorne J, Jabs D, Belfort R, Dick A, Gangaputra S, et al; Standardization of Uveitis Nomenclature (SUN) Project. The Standardization of Uveitis Nomenclature (SUN) Project. Development of a clinical evidence base utilizing informatics tools and techniques. Methods Inf Med 2013;52:259-65,S1−6. 7. Li Y, Lowder C, Zhang X, Huang D. Anterior chamber cell grading by optical coherence tomography. Invest Ophthalmol Vis Sci 2013;54:258– 65. 8. Ladas JG, Wheeler NC, Morhun PJ, Rimmer SO, Holland GN. Laser flare-cell photometry: methodology and clinical applications. Surv Ophthalmol 2005;50:27–47. 9. Konstantopoulou K, Del’Omo R, Morley AM, Karagiannis D, Bunce C, Pavesio C. A comparative study between clinical grading of anterior chamber flare and flare reading using the Kowa laser flare meter. Int Ophthalmol 2015;35:629–33. 10. Sahu S, Ram J, Bansal R, Pandav SS, Gupta A. Effect of topical ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09% on postoperative inflammation using laser flare photometry in patients having phacoemulsification.

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J Cataract Refract Surg 2015;41:2043–8. 11. El-Harazi SM, Ruiz RS, Feldman RM, Chuang AZ, Villanueva G. Quantitative assessment of aqueous flare: the effect of age and pupillary dilation. Ophthalmic Surg Lasers 2002;33:379–82. 12. Yu SY, Nam DH, Lee DY. Changes in aqueous concentrations of various cytokines after intravitreal bevacizumab and subtenon triamcinolone injection for diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2018;256:39–47. 13. Nagasaka Y, Ito Y, Ueno S, Terasaki H. Increased aqueous flare is associated with thickening of inner retinal layers in eyes with retinitis pigmentosa. Sci Rep 2016;6:33921. 14. Luo Z, Gardiner M. The incidence of intraocular foreign bodies and other intraocular findings in patients with corneal metal foreign bodies. Ophthalmology 2010;117:2218–21. 15. Gonul S, Bozkurt B, Okudan S. Metallic corneal foreign bodies: an occupational health hazard. Arq Bras Oftalmol 2014;77:411. 16. Heinz C, Zurek-Imhoff B, Koch J, Rösel M, Heiligenhaus A. Long-term reduction of laser flare values after trabeculectomy but not after cyclodestructive procedures in uveitis patients. Int Ophthalmol 2011;31:205– 10. 17. Agrawal R, Keane PA, Singh J, Saihan Z, Kontos A, Pavesio CE. Classification of semi-automated flare readings using the Kowa FM 700 laser cell flare meter in patients with uveitis. Acta Ophthalmol 2016;94:e135–41. 18. Conart JB, Kurun S, Ameloot F, Tréchot F, Leroy B, Berrod JP. Validity of aqueous flare measurement in predicting proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Acta Ophthalmol 2017;95:e278–83. 19. Ohara K, Okubo A, Miyazawa A, Miyamoto T, Sasaki H, Oshima F. Aqueous flare and cell measurement using laser in endogenous uveitis patients. Jpn J Ophthalmol 1989;33:265–70. 20. Sawa M. Laser flare-cell photometer: principle and significance in clinical and basic ophthalmology. Jpn J Ophthalmol 2017;61:21–42. 21. Lages V, Gehrig B, Herbort CP Jr. Laser flare photometry: a cost-effective method for early detection of endophthalmitis after intravitreal injection of anti-VEGF agents. J Ophthalmic Inflamm Infect 2018;8:23. 22. Küchle M, Nguyen NX, Naumann GO. Aqueous flare following penetrating keratoplasty and in corneal graft rejection. Arch Ophthalmol 1994;112:354–8. 23. Eiferman RA, Schulz GS, Nordquist RE, Waring GO. Corneal wound healing and its pharmacologic modification after refractive keratotomy. In: Waring GO, editor. Refractive Keratotomy for myopia and astigmatism. 3th ed. St Louis: Mosby; 1992. p. 749−77. 24. Rosenbaum JT, Tammaro J, Robertson JE Jr. Uveitis precipitated by nonpenetrating ocular trauma. Am J Ophthalmol 1991;112:392–5. 25. Streilein JW. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879–89. 26. Taylor AW. Ocular immune privilege. Eye (Lond) 2009;23:1885–9. 27. Abudou M, Wu T, Evans JR, Chen X. Immunosuppressants for the prophylaxis of corneal graft rejection after penetrating keratoplasty. Cochrane Database Syst Rev 2015;(8):CD007603. 28. Zhang T, Li Z, Liu T, Li S, Gao H, Wei C, et al. Cyclosporine a drugdelivery system for high-risk penetrating keratoplasty: Stabilizing the intraocular immune microenvironment. PLoS One 2018;13:e0196571.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Lazer flare fotometri ile korneal yabancı cisim sonrası kan-aköz bariyerinde bozulmanın gösterilmesi Dr. İsmail Umut Onur, Dr. Sibel Zırtıloğlu, Dr. Ozan Sonbahar, Dr. Ercan Çavuşoğlu, Dr. Ulviye Yiğit Sağlık Bilimleri Üniversitesi, İstanbul Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Göz Hastalıkları Kliniği, İstanbul

AMAÇ: Metalik yabancı cisim maruziyeti sonrası oluşan korneal yaralanmalarda lazer fotometri kullanarak ön kamara flare değişikliklerini değerlendirmek. GEREÇ VE YÖNTEM: Bir gözünde yabancı cisim yaralanması olan 54 hastanın sağlıklı gözü karşılaştırmalı, gözlemsel ve kesitsel bir çalışmada incelendi. Flaredeki değişkenlik demografik özellikler, önceki maruziyetlerin öyküsü, korneal yabancı cismin yaralı korneadaki yeri ve penetrasyonuna göre analiz edildi. BULGULAR: Korneal yabancı cisim gelen gözlerde ortalama flaremetre değeri diğer kontrollere göre anlamlı derecede yüksekti (sırasıyla, 11.35±14.17 ph/ms ve 6.30±3.81 ph/ms) (p=0.014). Daha önce birden fazla korneal yabancı cisim çıkarılması öyküsü olan gözlerde, flaremetrenin ortalama değeri diğerlerinden anlamlı derecede düşüktü (p=0.029). TARTIŞMA: Korneanın yabancı cisme maruz kalmasıyla flare değeri artar. Bununla birlikte, daha önce birçok korneal yabancı cisme maruz kalma durumunda, flare değeri muhtemelen korneanın duyarsızlaştırılmasından dolayı nispeten düşük olabilir. Anahtar sözcükler: Korneal yabancı cisim; lazer flare fotometri; ön kamara reaksiyonu. Ulus Travma Acil Cerrahi Derg 2020;26(4):568-573

doi: 10.14744/tjtes.2019.88560

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ORIGIN A L A R T IC L E

How important is susceptibility-weighted imaging in mild traumatic brain injury? Tuğba Eldeş, M.D.,1 Fatma Beyazal Çeliker, M.D.,1 Özlem Bilir, M.D.,2 Özcan Yavaşi, M.D.,2 Arzu Turan, M.D.,1 Uğur Toprak, M.D.3

Gökhan Ersunan, M.D.,2

Department of Radiology, Recep Tayyip Erdoğan University Faculty of Medicine, Rize-Turkey

Department of Emergency Medicine, Recep Tayyip Erdoğan University Faculty of Medicine, Rize-Turkey

Department of Radiology, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir-Turkey

ABSTRACT BACKGROUND: Mild traumatic brain injury (mTBI) is a public health problem that is recognized as a “silent epidemic” in its late stages due to undiagnosed axonal damage rated 13 and above on the Glasgow Coma Scale (GCS). Injury-related microhemorrhages often cannot be detected on computed tomography (CT) scans and conventional magnetic resonance imaging (MRI). This study aims to investigate whether susceptibility-weighted imaging is feasible in mTBI patients. METHODS: Fifty-eight patients with GCS scores of 14 and 15 and with symptoms of brief mental fogs, impairment of concentration, memory loss, headache, dizziness, or imbalance after brain injury were examined at the emergency service. A brain CT scan and MRI containing diffusion-weighted and susceptibility-weighted imaging (SWI) sequences were performed on the patients whose symptoms did not seem to alleviate after the sixth hour. Thirteen patients were excluded from this study because of advanced age, diabetes, a history of hypertension or its chronic sequelae, or acute cerebrovascular disease; 45 patients were included in this study. RESULTS: The patients’ CT results were normal, and no diffusion restrictions were observed. The SWI revealed microhemorrhages in seven patients (15.6%). Five of these patients had hyperintense areas in conventional sequences corresponding to the hemorrhages spotted in the SWI. In three of the five patients, these pockets of hemorrhages were higher in number and size in comparison with conventional in the SWI sequence. CONCLUSION: Susceptibility-weighted imaging, which can be used to assess the presence and severity of microhemorrhages due to diffuse axonal injury, is recommended for determining the cause of symptoms in patients with mTBI, to continue targeted treatment and prevent complications that may develop. Keywords: Axonal injury; microhemorrhage; mild traumatic brain injury; susceptibility-weighted.

INTRODUCTION Mild traumatic brain injury (mTBI) that arises from diffuse axonal injury has become a public health problem recognized as a “silent epidemic” owing to its parenchymal changes being difficult to diagnose.[1] Mild traumatic brain injury includes patients with a Glasgow Coma Scale score (GCS) of 13 and above and accounts for 75% of traumatic brain injuries (TBI).[2] Although brain computed tomography (CT) images of these patients may appear normal, somatic,

cognitive, or sensorial symptoms may be present. Findings that could corroborate that the symptoms are due to diffuse axonal damage may not be observed on conventional magnetic resonance imaging (MRI). Most of these symptoms, such as headaches, dizziness, short-term memory loss of fewer than 30 seconds, impaired concentration, insomnia, and depression, may subside within a few weeks. However, the symptoms of 10–20% of these patients may last for three months or more. This clinical entity is known as a persistent post-concussive syndrome (PPCS).[3–5] PPCS decreases

Cite this article as: Eldeş T, Beyazal Çeliker F, Bilir Ö, Ersunan G, Yavaşi Ö, Turan A, et al. How important is susceptibility-weighted imaging in mild traumatic brain injury?. Ulus Travma Acil Cerrahi Derg 2020;26:574-579. Address for correspondence: Tuğba Eldeş, M.D. Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Rize, Turkey Tel: +90 464 - 212 30 12 E-mail: eldestugba@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):574-579 DOI: 10.14744/tjtes.2019.35485 Submitted: 06.06.2019 Accepted: 20.11.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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the quality of life and may lead to anxiety, depression, and social dysfunction.[6] After cranial trauma, a CT can be used to assess parenchymal, subdural, and epidural hematomas. The non-invasiveness of brain CT, which also offers quick results, is more advantageous compared with other methods of diagnosis concerning defining acute traumatic lesions and indicating anatomic localization. However, the sensitivity of brain CT for the detection of non-hemorrhagic trauma is lower than that of conventional MRI.[7] Conventional MRI imaging is 30% more sensitive for the detection of diffuse axonal injuries (DAI) in mTBIs.[8] Diffuse axonal injury (DAI) is diagnosed by the presence of pockets of microhemorrhages in subcortical and periventricular white matter areas. FLAIR, one of the conventional MRI sequences, is better at detecting axonal injuries than the T2-weighted sequence (T2W). [9] However, hyperintense foci in FLAIR and T2W sequences cannot distinguish lesions due to aging or microvascular diseases from axonal damage.[10] In contrast, diffusion-weighted imaging (DWI) can differentiate between vasogenic edema and cytotoxic edema. Focal cytotoxic (diffusion restriction) edema regions can also be observed in DAI patients.[11] In serious cases of TBI, DWI can reveal the extent and size of abnormalities (diffusion restrictions in DAI patients) more precisely compared with T2W and FLAIR images.[12] However, to our knowledge, there are no published data to date, suggesting that DWI is useful in patients with mTBI. Susceptibility-weighted imaging (SWI) is a technique that makes use of the magnetic sensitivity difference among the tissues. SWI can also detect DAI related microhemorrhage sites six times more sensitively than conventional MRI sequences. [13] For mTBIs, there is a need for sequences that support conventional sequences and help confirm the diagnosis. This study investigates the effectiveness of the SWI sequence in detecting axonal injury in mTBI.

MATERIALS AND METHODS Approval for this study was obtained from Karadeniz Technical University’s Faculty of Medicine Ethics Committee (Approval No.: 2016/18). Patients admitted to our hospital’s emergency service over two years due to traumatic incidents, such as traffic accidents, falls or blows, were examined. Patients noted to have a Glasgow Coma Scale score of 13 and higher and a normal brain CT after the neurological examination were considered to have mTBI according to the framework[2] defined by Geurts et al. brain CT was requested if the patients had a loss of consciousness for more than five minutes, difficulty remembering pre-traumatic events after 30 minutes had elapsed, or a dangerous traumatic incident (motor vehicle accident, being thrown out of a vehicle, falling from a height of three feet or more, falling from five or more ladder steps). Fifty-eight patients with a normal CT scan but with post-traumatic headache, dizziness, memory loss of more than five minutes, impaired concentration, inUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

somnia and depression, or ataxia and mild drowsiness during the neurological examination were included in this study. The symptomatic treatment of patients was started after admission; neurological examinations were then repeated on the 3rd and 6th hour from admission. Brain MRI was performed for patients who did not respond to the symptomatic treatment after the 6th hour from admission had elapsed. DWI and SWI sequences were also added to the conventional sequences. Brain CT scans were performed using the Toshiba Alexion™ Advance (Toshiba Medical Systems Corporation, Nashua, Japan) computerized tomography device with 16 slices (field of view of 22 cm, 170 mA, 100 kV, thickness 5 mm, images reconstructed to a size of 1 mm). MRI scans were conducted with a Magnetom Aera (Siemens Healthcare, Germany) MRI device with 1.5 Tesla magnet power and 32-channel head coils. Brain MRI scans were performed with axial T1W (TR:417ms; TE:8.9ms, slice thickness 3 mm), T2W (TR:5480ms; TE:100ms, slice thickness 3 mm), FLAIR (TR:6000ms; TE:86ms; TI:2026ms, slice thickness 3 mm) SWI (TR:49ms; TE:40ms; flip angle 15°, slice thickness 2.5 mm) with maximum intensity projection (MIP) and DWI (EPI diffusion TE:75ms; TR:5100ms; slice thickness of 5), coronal T2W sequences. Radiological examinations were reviewed together by two radiologists who had at least 10 years of neuroradiology experience, and the results were accepted unanimously. Thirteen of the patients were excluded due to diffusion restrictions related to microvascular diseases such as hypertension, acute strokes, or a history of ischemic attacks in DWI, T2W and FLAIR sequences. The remaining 45 patients were included in the study. These patients had no other trauma history. No diffusion restrictions were observed on these patients’ brains; however, T2W and FLAIR images showed subcortical and periventricular white matter lesions. If the SWI showed no low signals of bleeding in the lesions, this was interpreted as a “secondary microvascular event or gliosis” and subsequently labeled “nonspecific;” if a low signal was noted, this was interpreted as a microhemorrhage secondary to axonal injury. The patients with microhemorrhage were given supportive treatments within a hospital environment until their symptoms showed improvement. Patients were assessed with neurological examinations for ongoing or new symptoms during follow-up every six months over two years. The Kolmogorov-Smirnov test was used to determine the appropriateness of the data to normal distribution. The test later revealed that the data did not align with the normal distribution. The trauma patterns, Glasgow Coma Scale values, admission symptoms, and SWI findings were categorized. The Chi-Square test was used to compare categorical data. De575

Eldeş et al. How important is susceptibility-weighted imaging in mild traumatic brain injury?

Table 1. Type of symptoms and findings symptoms Symptoms and findings

Nausea

25 55.6 0.52

Headache

16 35.6 0.31

Vertigo

18 40 0.39

Amnesia

7 15.6 0.54

Vomiting

5 11.1 0.90

Stupor

1 2.2 0.06

mographic data, such as information on age and gender, were retrieved. The median value (min.-max.) was obtained with descriptive statistics, as the data did not align with the normal distribution. If the P-value was less than 0.05, the results were considered significant.

RESULTS Twenty-three of the 45 patients were male (51.1%), 22 were female (48.9%), and their mean age was 47.93±21.49. There was no difference between the mean age of male patients (45, min. 18, max. 86) and female patients (51, min. 18, max. 99) (p=0.19). The most common form of trauma suffered by the patients was falls (62.2%). The most common symptom was nausea (55.6%) (Table 1). At the time of admission, the GCS was 15 in 44 patients and 14 in one patient. (a)

(e)

(b)

Table 2. Comparison of age, number of lesions on MRI, and lesion of the patients with microhemorrhage Patients Age DWI* T2* FLAIR* SWI* Boyut (years) artışı 1

21 – 4 4 6 +

70 – 2 2 2 –

59 – – – 1

78 – 4 4 6 +

67 – 2 2 2 +

82 – 2 2 2 –

67 – – – 5

*Number of lesions. MRI: Magnetic resonance imaging; DWI: Diffusion-weighted imaging; FLAIR: Fluid-attenuated inversion recovery; SWI: Susceptibility-weighted imaging.

The SWI showed hypo-intense, microhemorrhage areas in seven of the 45 patients (15.6%; Table 2). There was no restricted diffusion in any focus. In five of the seven patients, these areas were hyper-intense in T2W and FLAIR. In three of these patients, the microhemorrhage fields shown by the SWI were significantly larger in size and number than the hyper-intense areas in FLAIR (Figs. 1 and 2). In the other two patients, the SWI showed hypo-intense microhemorrhage areas, while there were no intensity changes in FLAIR and T2W (Fig. 2 and 3). The neurological examination performed at (c)

(f)

(d)

(g)

Figure 1. A male case with mTBI. Pathology was not observed in CT. In MRI: (a) T2W and (b) FLAIR; hyperintense nonspecific were observed in the corpus callosum genus and left centrum semiovale (arrows), while in the (c) SWI-MIP and (d-g) SWI; there are increases of number and size of the lesions: bilateral frontal white matters and left para hippocampal area (arrows).

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Eldeş et al. How important is susceptibility-weighted imaging in mild traumatic brain injury? (a)

(b)

(c)

Figure 2. A female case with mTBI. Pathology was not observed in T2W and FLAIR (a, b). SWI MIP images show a lesion at the level of in the left centrium semiovale (c) (arrows).

ment within this period. We recommended that they avoid life-threatening risks that could result in recurrent trauma after their discharge. Neurological examinations were repeated over a period of six months for two years; there were no long-term complications noted.

Figure 3. A male case with mTBI. SWI MIP image shows microhemorrhage lesions at the bulb level (arrows).

six-month intervals for two years revealed the development of no new finding in any of the patients.

DISCUSSION In the present study, there were no specific findings in the brain CT and conventional MRI examinations of patients with posttraumatic mTBI. However, there were heterogeneous symptoms. In these patients, microhemorrhage was detected in the SWI sequence in localizations consistent with nonspecific changes in T2W and FLAIR. As opposed to conventional sequences, lesions were more common and larger in SWI. Thus, it is possible to say that symptoms had developed due to DAI. With the diagnosis of posttraumatic DAI, the patients’ stays in the hospital were extended, and they were kept under surveillance for 24 hours. They received conservative treatUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

DAI is suspected in the presence of heterogeneous symptoms in patients with mTBI.[14] The DAI can be concentrated in a small area or may extend over a wide area along the diffuse axon. The use of advanced MRI techniques has recently provided important benefits because the absence of symptomatic findings in CT or conventional MRI cannot exclude the possibility that the symptoms do not have an organic background in mTBI patients. With the SWI sequence, the size of the microhemorrhage and the presence of additional foci can be shown more clearly, and it is also useful in the identification of traumatic microhemorrhages and hemorrhagic DAI lesions in chronic stage mTBI patients.[15] Furthermore, microhemorrhages have been the subject of research in many other diseases, such as strokes, amyloid beta-related angiitis, and Binswanger’s disease.[16–18] The presence and prevalence of DAI in mTBI is an important indicator of long-term cognitive and neuropsychiatric disorders.[19,20] Athletes, such as boxers and football players, have been diagnosed with the progressive neurodegenerative syndrome, also called chronic traumatic encephalopathy, after postmortem histochemical and immunochemical tissue analyses of the brain following repeated blunt head traumas were performed. Suicides were also reported in some cases of the disorder.[21] Kanayama et al.[22] found changes in the cortical and hippocampal cytoskeletal proteins in recurrent mTBIs not occurring with a single trauma. The number of studies confirming that the sensitivity of MRI in showing microhemorrhages is higher in T2* and SWI sequences is increasing. Although the T2* sequence is sensitive in the detection of microhemorrhages, microhemorrhages cannot be detected with this sequence in 25% of patients with cerebral amyloid angiopathy.[23] The SWI sequence is 577

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a new sequence that creates contrasts using the magnetic susceptibility differences of the tissues and is 25% better than the T2* sequence for detecting hemorrhages and 37.5% better than the conventional sequences.[24] In our patients, intense nonspecific changes were observed in conventional sequences, and the SWI detected microhemorrhage areas in only two of the patients. According to the American College of Radiology (ACR) Appropriateness Criteria, among imaging modalities, MRI is ‘usually not appropriate’ for imaging minor and mild head traumas with a GCS of >13.[25] Similarly, Tavender et al.[26] did not consider MRI as an appropriate initial imaging modality in this patient group. In the present study, the patients with mTBI had a GCS of ≥14. The patients had subjective complaints, and some (15.6%) patients also presented with bleeding foci in the white matter. Thus, we consider that performing MRI and especially obtaining the SWI sequence might be beneficial in mTBI cases with subjective complaints. The current study has few limitations, such as its single-centered design and relatively small sample size. Furthermore, including a control group comprising individuals with similar symptoms to neuropsychiatric-cognitive disorder but no history of trauma would have provided more interesting results. However, we were not able to achieve this due to the difficulty of recruiting volunteers. Nevertheless, it seems clear that these individuals would not have as much hemosiderin accumulation as mTBI patients. To conclude, the SWI sequence is one of the new MRI sequences that may be helpful in determining the diagnostic and treatment modalities in patients with mTBI due to the additional data it provides. It can also aid in patient follow-up. Routine use of this sequence in patients with mTBI can help achieve short-term stabilization of patients during the healing process and, in the long term, prevent complications through protection from recurrent trauma if DAI is present. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: T.E., F.B.Ç.; Design: T.E., Ö.B.; Supervision: T.E.; Materials: Ö.B., Ö.Y.; Data: T.E., G.E., F.B.Ç.; Analysis: G.E., Ö.Y.; Literature search: T.E., A.T.; Writing: T.E., U.T., A.T.; Critical revision: U.T. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Vaishnavi S, Rao V, Fann JR. Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic. Psychosomatics 2009;50:198–205.

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2. Geurts BH, Andriessen TM, Goraj BM, Vos PE. The reliability of magnetic resonance imaging in traumatic brain injury lesion detection. Brain Inj 2012;26:1439–50. 3. Alexander MP. Mild traumatic brain injury: pathophysiology, natural history, and clinical management. Neurology 1995;45:1253–60. 4. Bigler ED. Neuropsychology and clinical neuroscience of persistent postconcussive syndrome. J Int Neuropsychol Soc 2008;14:1–22. 5. Belanger HG, Curtiss G, Demery JA, Lebowitz BK, Vanderploeg RD. Factors moderating neuropsychological outcomes following mild traumatic brain injury: a meta-analysis. J Int Neuropsychol Soc 2005;11:215– 27. 6. Feinstein A, Ouchterlony D, Somerville J, Jardine A. The effects of litigation on symptom expression: a prospective study following mild traumatic brain injury. Med Sci Law 2001;41:116–21. 7. Lee H, Wintermark M, Gean AD, Ghajar J, Manley GT, Mukherjee P. Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. J Neurotrauma 2008;25:1049–56. 8. Haacke EM, Duhaime AC, Gean AD, Riedy G, Wintermark M, Mukherjee P, Brody DL, DeGraba T, Duncan TD, Elovic E, Hurley R, Latour L, Smirniotopoulos JG, Smith DH. Common data elements in radiologic imaging of traumatic brain injury. J Magn Reson Imaging 2010;32:516−43. 9. Ashikaga R, Araki Y, Ishida O. MRI of head injury using FLAIR. Neuroradiology 1997;39:239–42. 10. Trifan G, Gattu R, Haacke EM, Kou Z, Benson RR. MR imaging findings in mild traumatic brain injury with persistent neurological impairment. Magn Reson Imaging 2017;37:243–51. 11. Galloway NR, Tong KA, Ashwal S, Oyoyo U, Obenaus A. Diffusionweighted imaging improves outcome prediction in pediatric traumatic brain injury. J Neurotrauma 2008;25:1153–62. 12. Liu W, Soderlund K, Senseney JS, Joy D, Yeh PH, Ollinger J, et al. Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury. Radiology 2016;278:536−45. 13. Mechtler LL, Shastri KK, Crutchfield KE. Advanced neuroimaging of mild traumatic brain injury. Neurol Clin 2014;32:31–58. 14. Sharp DJ, Ham TE. Investigating white matter injury after mild traumatic brain injury. Curr Opin Neurol 2011;24:558–63. 15. Niogi SN, Mukherjee P, Ghajar J, Johnson C, Kolster RA, Sarkar R, et al. Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol 2008;29:967−73. 16. Bian W, Hess CP, Chang SM, Nelson SJ, Lupo JM. Susceptibilityweighted MR imaging of radiation therapy-induced cerebral microbleeds in patients with glioma: a comparison between 3T and 7T. Neuroradiology 2014;56:91–6. 17. Choi P, Ren M, Phan TG, Callisaya M, Ly JV, Beare R, et al. Silent infarcts and cerebral microbleeds modify the associations of white matter lesions with gait and postural stability: population-based study. Stroke 2012;43:1505−10. 18. Hanyu H, Tanaka Y, Shimizu S, Takasaki M, Fujita H, Kaneko N, et al. Cerebral microbleeds in Binswanger’s disease: a gradient-echo T2*-weighted magnetic resonance imaging study. Neurosci Lett 2003;340:213−6. 19. Adams JH, Graham DI, Murray LS, Scott G. Diffuse axonal injury due to nonmissile head injury in humans: an analysis of 45 cases. Ann Neurol 1982;12:557–63. 20. Medana IM, Esiri MM. Axonal damage: a key predictor of outcome in human CNS diseases. Brain 2003;126:515–30.

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21. Casson IR, Pellman EJ, Viano DC. Chronic traumatic encephalopathy in a National Football League player. Neurosurgery 2006;58:E1003. 22. Kanayama G, Takeda M, Niigawa H, Ikura Y, Tamii H, Taniguchi N, et al. The effects of repetitive mild brain injury on cytoskeletal protein and behavior. Methods Find Exp Clin Pharmacol 1996;18:105−15. 23. Haacke EM, DelProposto ZS, Chaturvedi S, Sehgal V, Tenzer M, Neelavalli J, et al. Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. AJNR Am J Neuroradiol 2007;28:316−7. 24. Wycliffe ND, Choe J, Holshouser B, Oyoyo UE, Haacke EM, Kido DK. Reliability in detection of hemorrhage in acute stroke by a new three-

25. American College of Radiology, ACR Appropriateness Criteria. Clinical Condition: Head Trauma. Available at: https://acsearch.acr.org/ docs/69481/Narrative/. Accessed February, 2020. 26. Tavender EJ, Bosch M, Green S, O’Connor D, Pitt V, Phillips K, et al. Quality and consistency of guidelines for the management of mild traumatic brain injury in the emergency department. Acad Emerg Med 2011;18:880−9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Hafif travmatik beyin hasarında duyarlılık ağırlıklı görüntüleme ne kadar önemli? Dr. Tuğba Eldeş,1 Dr. Fatma Beyazal Çeliker,1 Dr. Özlem Bilir,2 Dr. Gökhan Ersunan,2 Dr. Özcan Yavaşi,2 Dr. Arzu Turan,1 Dr. Uğur Toprak3 1 2 3

Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Rize Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Rize Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Eskişehir

AMAÇ: Hafif travmatik beyin hasarı (mTBI), Glascow Koma Skalası (GCS) 13 ve üzerinde olan, tanı alamayan aksonal hasar nedeniyle geç dönemde ‘sessiz epidemik’ olarak adlandırılan bir halk sağlığı sorunudur. Bilgisayarlı tomografi (BT) ve konvansiyonel manyetik rezonans gorüntülemede (MRG) hasara bağlı mikrohemorajiler çoğunlukla görüntülenememektedir. Bu çalışmada, MRG sekanslarından duyarlılık ağırlıklı görüntülemenin (SWI) mTBI olgularında uygulanabilir olup olmadığının araştırılması amaçlanmıştır. GEREÇ VE YÖNTEM: Beyin hasarı sonrası GCS’si 14 ve 15 olan, kısa süreli bilinç bulanıklığı, konsantrasyon zorluğu, hafıza kaybı, baş ağrısı, baş dönmesi, dengesizlik gibi semptomları bulunan 58 hasta acil serviste değerlendirildi. Altıncı saatten sonra semptomları gerilemeyen hastalara beyin BT ve difüzyon ağırlıklı ve SWI sekanslarını içeren MRG çekildi. On üç hasta, ileri yaş, diyabet, hipertansiyon öyküsü ve kronik sekel değişiklikler, akut serebrovasküler hastalık bulgusu bulunması nedeniyle dışlandı. BULGULAR: Olguların BT bulguları normaldi, difüzyon ağırlıklı sekanslarda difüzyon kısıtlanması izlenmedi. Yedi hastada (%15.6) SWI’da mikrohemoraji odakları saptandı. Bunların beşinde SWI’daki mikrohemoraji alanları konvansiyonel sekanslarda hiperdens odaklar olarak izlendi. Bu olguların üçünde ise mikrohemoraji odakları sayı ve boyut açısından SWI sekansında T2A ve FLAIR’a göre artmıştı. TARTIŞMA: Diffüz aksonal hasara bağlı mikrohemoraji varlığını ve ciddiyetini değerlendirebilen SWI, hafif beyin hasarlı (mTBI) hastalarda semptomların nedenini açıklamak, nedene yönelik tedavisini sürdürmek ve gelişebilecek komplikasyonları önlemek için tavsiye edilir. Anahtar sözcükler: Aksonal hasar; duyarlılık ağırlıklı; hafif travmatik beyin hasarı; mikrohemoraji. Ulus Travma Acil Cerrahi Derg 2020;26(4):574-579

doi: 10.14744/tjtes.2019.35485

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ORIGIN A L A R T IC L E

Can the C-reactive protein-to-plasma albumin ratio be an alternative scoring to show mortality and morbidity in patients with colorectal cancer? Yeliz Şahiner, M.D.,1

Murat Baki Yıldırım, M.D.2

Department of Anesthesiology and Reanimation, Hitit University Faculty of Medicine, Çorum-Turkey

Department of General Surgery, Hitit University Faculty of Medicine, Çorum-Turkey

ABSTRACT BACKGROUND: This study aims to demonstrate the sensitivity and specificity of C-reactive protein to plasma albumin (CRP/ALB) ratio in predicting morbidity and mortality in patients operated for colorectal cancer followed up in the intensive care unit by comparing it with current scoring systems. METHODS: The data of patients who underwent surgery for colorectal cancer and hospitalized in the intensive care unit between 2015–2018 with available data were retrospectively analyzed in this study. The CRP/ALB ratio, the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) prepared for both gastrointestinal and colorectal surgery, and the Association of Coloproctology of Great Britain and Ireland (ACPGBI-CRC) scoring system prepared for colorectal patients, were compared to determine their success in predicting mortality and morbidity. RESULTS: A total of 119 patients were included in this study. Mortality was observed in nine patients and morbidity was observed in 38 patients. When compared with P-POSSUM, which is the only scoring system showing morbidity, the CRP/ALB ratio was found to have a high prediction accuracy. The C reactive protein to plasma albumin ratio values was found to have lower power than P-POSSUM, CR-POSSUM and ACPGBI-CRC. CONCLUSION: Although scoring systems are useful in predicting morbidity and mortality in colorectal patients, they are difficult to use in practice since they include many parameters. that the findings obtained in this study suggest that the CRP/ALB ratio, which can be calculated without any additional cost, may help the clinician predict mortality and especially morbidity. Keywords: Aged; colorectal cancer; intensive care units; organ dysfunction scores; prognosis; ROC curve.

INTRODUCTION Malignancy patients are of vital importance in general surgery practice. The vast majority of malignancy patients is of advanced age and naturally has many comorbid diseases. Preoperative and postoperative mortality and morbidity rates of individuals in the advanced age group are higher than that of the younger age group. Before scheduling a major surgical intervention, it is important to know the perioperative morbidity or mortality of patients concerning taking measures against complications that may develop. Various scoring systems are

used to predict morbidity and mortality of such high-risk patients before surgery or during intensive care follow-ups after surgery. The common characteristic of these scoring systems is to predict potential mortality and morbidity by calculating the various measurement and laboratory values of the patient within a certain scale and to draw the attention of the clinician. Otherwise, they do not have any therapeutic property. The group of patients with colorectal malignancy is also in the risk group for morbidity and mortality because of both age and diseases. Due to the complications that may develop in

Cite this article as: Şahiner Y, Yıldırım MB. Can the C-reactive protein-to-plasma albumin ratio be an alternative scoring to show mortality and morbidity in patients with colorectal cancer?. Ulus Travma Acil Cerrahi Derg 2020;26:580-585. Address for correspondence: Yeliz Şahiner, M.D. Hitit Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Çorum, Turkey Tel: +90 364 - 219 30 00 E-mail: yelizsahiner@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):580-585 DOI: 10.14744/tjtes.2020.34412 Submitted: 17.02.2020 Accepted: 08.05.2020 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Şahiner et al. Can the CRP/ALB ratio be an alternative scoring to show mortality and morbidity in patients with colorectal cancer?

the follow-up and treatment of such patients, their lengths of hospital stay are prolonged, additional care and intervention costs are required, and the initiation of patients on treatments such as chemotherapy is delayed.[1] One of the commonly used scoring systems to predict morbidity and mortality of such risky patients is the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM).[2] POSSUM is a very comprehensive scaling system consisting of twelve physiological and six operative parameters.[3] Although POSSUM makes it easy to predict mortality and morbidity, it is often difficult to calculate a total of 18 parameters in the daily routine. Therefore, various disease-specific modifications have been developed to facilitate calculations. Scoring modifications specific to diseases and surgical procedures to be performed, such as V-POSSUM for vascular surgical interventions, Cr-POSSUM for colon surgery, P-POSSUM for gastrointestinal surgery, have been made.[4,5] Cr-POSSUM, customized for colorectal surgery patients, includes six physiological parameters and four operative parameters. Therefore, it is easier to calculate.[6] Another scoring system published by the Association of Coloproctology of Great Britain in 2003 for use in colorectal surgery patients and updated in 2010 with a high accuracy rate is the Association of Coloproctology of Great Britain and Ireland (ACPGBI-CRC).[7] In this scoring system, five parameters, including the American Society of Anesthesiologists (ASA) risk assessment, are calculated. The small number of parameters to be analysed has naturally increased its clinical use. Recently, it is popular to analyse the C-reactive protein (CRP) to plasma albumin (ALB) ratio, which has been argued to have a predictive value to predict morbidity and mortality in intensive care patients.[8] CRP is an acute-phase protein produced by stimulation of various cytokines in response to infection, ischemia, trauma and other inflammatory conditions. On the other hand, low serum albumin is known to be associated with poor prognosis and mortality.[9] Both CRP and ALB are practical, inexpensive and easily accessible tests routinely used in ICU patients. In this study, the sensitivity and specificity of the CRP/ALB ratio in predicting postoperative morbidity and mortality in patients undergoing colorectal surgery were investigated by comparing it with P-POSSUM, Cr-POSSUM, and ACPGBICRC scores.

MATERIALS AND METHODS The data of patients who were admitted to the general surgery outpatient clinic of Hitit University Faculty of Medicine for colorectal malignancy, operated and followed up in the intensive care unit between January 2015 and November 2018 were retrospectively investigated from the archive and hospital computer database. Patients under the age of 18 years, patients who did consent their information to be used for this Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

study, patients whose files could not be completely reached, and patients who underwent colorectal surgery but not admitted to the intensive care unit were excluded from this study. The demographic data, ASA scores, biochemical values, comorbidities, vital signs, and operative information in the operative notes of the patients were collected. Recording the levels of C-reactive protein (CRP) and plasma albumin (ALB) taken in the first 24 hours postoperatively from the patient files, the CRP/ALB ratio of all patients was calculated. Using the infrastructure of the website http://www.riskprediction. org.uk, P-POSSUM, Cr-POSSUM and ACPGBI-CRC scores of all patients were calculated with the help of the data in the patient files. The parameters used to calculate all scores are given in Table 1. The morbidity and mortality developed in the patients were noted. For the morbidity and mortality, the first 30 days after surgery were considered in the calculations.

Institutional Review Board (IRB) This study was conducted according to Helsinki human declaration guides. Written informed consent is taken. Institutional Review Board approved this study (Hitit University, Erol Olçok Training and Research Hospital, Date: 31.01.2020, IRB Number: 40600303-000-944).

Statistical Method The statistical analyses of the data obtained were carried out using SPSS v.22.0 (SPSS Inc., Chicago, IL, USA, Licensed to Hitit University). The frequency and mean values of the demographic data were calculated. The predictivity scores, CRP/ ALB ratio and postoperative morbidity and mortality rates were compared. Whether CRP/ALB and P-POSSUM scores could be prognostic markers to compare morbidity and whether CRP/ALB, ACPGBI-CRC, P-POSSUM, CR-POSSUM scores could be prognostic markers to compare mortality were analyzed with Receiver Operating Characteristic (ROC) curve. The area under the ROC curve (AUC) was evaluated as 0.9–1: excellent, 0.8–0.9: good, 0.7–0.8: moderate, 0.6–0.7: weak, and 0.5–0.6: failed. The Youden index (maximum sensitivity and selectivity) was used to determine the optimal cut-off point after the ROC analysis. Sensitivity, selectivity, positive-negative predictive values, and likelihood ratio (+) values were calculated by using cut-off points after the ROC analysis to determine the discriminatory power of the marker. The level of statistical significance was set to p<0.05.

RESULTS The data of a total of 119 patients who met the study criteria were evaluated. Of the patients, 34.45% (n=41) were female, 65.55% (n=78) were male, and the mean age was 68 (years). Considering the surgical procedure performed, it was found that of the patients, 32.7% (n=39) underwent right hemi581

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Table 1. Parameters of the scoring systems

P-possum Cr-Possum ACPGBI-CRC

Physiological parameters

Age

Cardiac

ASA score

Respiratory

Systolic blood pressure

Cancer stage

ECG Pulse

Systolic blood pressure

Pulse Urea

Haemoglobin

White blood cell

Urea Sodium Potassium

Glasgow Coma Score

Operative parameters

Type of surgery

Number of procedures

Contamination

Urgency

Blood loss

Presence of malignancy

Contamination Urgency

Presence of malignancy

Urgency ACPGBI-CRC: Association of Coloproctology of Great Britain and Ireland; ECG: Electrocardiogram.

colectomy, 12.6% (n=15) underwent left hemicolectomy, 6.7% (n=8) underwent transverse colectomy, 32.7% (n=39) underwent anterior resection, 13.4% (n=16) underwent low anterior resection, and 0.8% (n=1) underwent total colectomy surgery. It was found that 31.9% (n=38) of the patients developed postoperative morbidity. In addition, mortality was observed in 7.5% (n=9) of the patients within 30 days Table 2. ROC curve results, sensitivity, specificity, positivenegative predictive and likelihood ratio (+) values for morbidity AUC (95% CI)

CRP/ALB P-POSSUM 0.817 (0.731–0.904)

0.734 (0.635–0.833)

P–values <0.001 <0.001

postoperatively. The CRP/ALB ratio and P-Possum score were compared to predict morbidity. The cut-off value of the CRP/ALB ratio for morbidity was 6.6675. Based on this cutoff value, it was found to predict morbidity with a sensitivity of 0.763 and a specificity of 0.790. These values were 0.605 and 0.814 for P-Possum, respectively (p<0.05). The AUC was 0.817 for CRP/ALB, while the AUC was 0.734 for P-Possum (Table 2). In the prediction of the mortality, the cut-off value of the CRP/ALB ratio was determined as 13.66. The CRP/ ALB ratio predicted mortality with a sensitivity of 0.777 and a specificity of 7.790, while these values were 0.888 and 0.900 for ACPGBI-CRC, 0.777 and 0.763 for P-POSSUM, 0.888 and 0.700 for CR-POSSUM, respectively (p<0.05). The AUC was 0.789 for CRP/ALB, 0.919 for ACPGBI-CRC, 0.795 for PPOSSUM and 0.838 for CR-POSSUM (Table 3).

Cut–off 6.675 44.25

DISCUSSION

Sensitivity

0.763 (0.594–0.879)

0.605 (0.434–0.755)

Specificity

0.790 (0.682–0.869)

0.814 (0.710–0.889)

PPV

0.630 (0.475–0.764)

0.605 (0.434–0.755)

NPV

0.877 (0.774–0.938)

0.814 (0.710–0.889)

LR +

3.64 (2.30–5.75)

3.26 (1.93–5.51)

The surgical procedures performed for colorectal malignancies are of great importance in current practice. Since most of the patients are in the geriatric age group, morbidity and mortality are often seen in the postoperative follow-up period.[10] In this study, the mean age of the patients was 68 years. In this study, not all subjects underwent elective operations. There were eight patients that were classified as “urgent”. Among these patients, six patients underwent sigmoid resection, one hemicolectomy, and one transverse colectomy. Of the 26 patients that were classified as “emergency”, five underwent right hemicolectomy, one transverse

ROC: Receiver Operating Characteristic; CRP/ALB: C-reactive protein to plasma albumin; POSSUM: Physiological and operative severity score for the enumeration of mortality and morbidity; AUC: Area under the curve; CI: Confidence interval; PPV: Positive predictive value; NPV: Negative predictive value; LR: Likelihood ratio.

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Table 3. ROC curve results, sensitivity, specificity, positive-negative predictive and likelihood ratio (+) values for mortality AUC (95% CI) P values

CRP/ALB

ACPGBI–CRC

P–POSSUM EX

CR–POSSUM

0.789 (0.613–0.965)

0.919 (0.822–1.000)

0.795 (0.661–0.930)

0.838 (0.714–0.962)

0.004

<0.001

0.003

0.001

Cut–off 13.66 0.0955 0.034 0.0435 Sensitivity

0.777 (0.401–0.960)

0.888 (0.506–0.994)

0.777 (0.401–0.960)

0.888 (0.506–0.994)

Specificity

0.790 (0.700–0.860)

0.900 (0.824–0.946)

0.763 (0.671–0.837)

0.700 (0.604–0.781)

PPV

0.233 (0.106–0.427)

0.421 (0.211–0.660)

0.212 (0.096–0.393)

0.195 (0.093–0.353)

NPV

0.977 (0.913–0.996)

0.990 (0.937–0.999)

0.976 (0.910–0.995)

0.987 (0.920–0.999)

LR +

3.71 (2.24–6.15)

8.88 (4.84–16.29)

3.29 (2.02–5.34)

2.96 (2.05–4.27)

hemicolectomy, four low anterior resection and 16 sigmoid resection. The differentiation of the surgical timing status of these patients would not have improved statistical significance. Hence, these patients were not divided into two separate groups. Also, whether the patients are classified as an emergency or elective does not affect the pattern or results of the study. If we are to elaborate on why it would not do so, the parameters used in the calculation of scoring systems already question whether the operation is elective, emergency, or urgent, and assigns a risk score accordingly. Therefore, the score will be lower if the operation is classified as elective and higher if classified as an emergency. Considering all these, it can be inferred that the “emergency” or “elective” status of the patients will not hinder the utility of CRP/albumin ratio in scoring systems in predicting morbidity and mortality. High-risk patients presenting with postoperative morbidity increase the cost of care due to prolonged length of stay in intensive care, additional interventions and treatments. For this reason, although many scoring systems have been devel(a)

Source of the Curve CRP/Alb P-POSSUM Reference Line

0.6

0.4

0.2

ROC Curve

1.0

Source of the Curve CRP/Alb ACPGBI-CRC P-POSSUM EX CR-POSSUM Reference Line

0.8

Sensitivity

0.8

0.0 0.0

Recent studies have shown that the CRP/ALB ratio is very reliable in predicting 30-day mortality in patients followed up in the intensive care unit.[13] Moreover, the CRP/ALB ratio (b)

ROC Curve

1.0

oped to predict morbidity and mortality for ICU patients, the high number of and complex parameters used often prevent them from being used in practice. Therefore, Prytherch et al.[11] developed a scoring system in 1998 to predict morbidity and mortality in surgical patients. Although P-POSSUM predicts mortality for surgical patients with high accuracy, Tekkis et al.,[5] who needed a scoring system specific to colorectal patients, developed the CR-POSSUM scoring system. CR-Possum consists of six physiological and four operative parameters and predicts postoperative mortality with high accuracy. Since the scoring systems include many parameters that are not specific to patients with colorectal cancer, a 5-parameter ACPGBI-CRC scoring system, including the patient’s age, ASA score, stage of colorectal cancer, whether the surgery is urgent and the type of surgery planned to be performed has been developed.[12]

0.6

0.4

0.2

0.4 0.6 1-Specificity

0.8

1.0

Diagonal segments are produced by ties

0.0 0.0

0.2

0.4 0.6 0.8 1-Specificity Diagonal segments are produced by ties

1.0

Figure 1. Sensitivity and specificity rates. (a) ROC curve of CRP/ALB and P-POSSUM. (b) ROC curve of all scoring systems on mortality.

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has been used to predict prognosis in patients with colorectal cancer.[14] We analyzed the postoperative 12th hour’s blood samples for calculating the CRP/ALB ratio. In the intensive care practice of our institution, for all patients, samples are retrieved for the required culture exams at the time of admission to the intensive care unit and routine blood samples are retrieved 12 hours after admission. Since our study was retrospective in nature, we were able to access the 12th-hour blood test results of our subjects. In other words, we were not able to access the 24th- or 48th-hour blood test results. Therefore, there was no specific reason for using postoperative 12th-hour blood test results other than that these results were available in patient files. When P-POSSUM and the CRP/ALB ratio that predicts morbidity in colorectal cancer patients were compared in this retrospective study, the AUC was calculated as 0.817, considering the optimal cut-off value for CRP/ALB ratio 6.675. This result was found to be higher than the value of 0.734 calculated for P-POSSUM. P-POSSUM appears to be more valuable in predicting morbidity (Fig. 1). There are studies comparing these three scoring systems in predicting mortality. ACPBGI-CRC has been shown to be more valuable than CR-POSSUM and P-POSSUM.[15] In this study, ACPBGI-CRC was also found to be the most reliable test for predicting mortality. When the cut-off value was taken as 13.66 for the CRP/ALB ratio, the AUC was calculated as 0.789 (Fig. 1). Although the specificity of CRP/ALB was higher than that of P-POSSUM and CR-POSSUM, its sensitivity was low. Since the number of mortality was nine in this study, the margin of error of one patient resulted in a statistically significant difference. The limited number of patients included in this study, the inclusion of only the patients admitted to the intensive care unit, and the retrospective nature of the study were among the limitations of this study. We are of the opinion that prospective observational studies to be conducted with a larger sample size may more explicitly demonstrate the power of these parameters in predicting morbidity and mortality.

Conclusion Although scoring systems are useful in predicting morbidity and mortality in colorectal patients, they are difficult to use in practice since they include many parameters. The findings obtained in this study suggest that the CRP/ALB ratio, which can be calculated without any additional cost, may help the clinician predict mortality and especially morbidity.

Acknowledgements

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Y.Ş., M.B.Y.; Design: Y.Ş., M.B.Y.; Supervision: Y.Ş., M.B.Y.; Fundings: Y.Ş., M.B.Y.; Materials: Y.Ş., M.B.Y.; Data: Y.Ş.; Analysis: Y.Ş., M.B.Y.; Literature search: Y.Ş., M.B.Y.; Writing: Y.Ş., M.B.Y.; Critical revision: Y.Ş. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Hendren S, Birkmeyer JD, Yin H, Banerjee M, Sonnenday C, Morris AM. Surgical complications are associated with omission of chemotherapy for stage III colorectal cancer. Dis Colon Rectum 2010;53:1587−93. 2. Jones HJ, de Cossart L. Risk scoring in surgical patients. Br J Surg 1999;86:149−57. 3. Copeland GP, Jones D, Walters M. POSSUM: a scoring system for surgical audit. Br J Surg 1991;78:355−60. 4. Tekkis PP, McCulloch P, Poloniecki JD, Prytherch DR, Kessaris N, Steger AC. Risk-adjusted prediction of operative mortality in oesophagogastric surgery with O-POSSUM. Br J Surg 2004;91:288−95. 5. Tekkis PP, Prytherch DR, Kocher HM, Senapati A, Poloniecki JD, Stamatakis JD, et al. Development of a dedicated risk-adjustment scoring system for colorectal surgery (colorectal POSSUM). Br J Surg 2004;91:1174−82. 6. Leung E, McArdle K, Wong LS. Risk-adjusted scoring systems in colorectal surgery. Int J Surg 2011;9:130−5. 7. Al-Homoud S, Purkayastha S, Aziz O, Smith JJ, Thompson MD, Darzi AW, et al. Evaluating operative risk in colorectal cancer surgery: ASA and POSSUM-based predictive models. Surg Oncol 2004;13:83−92. 8. Park JE, Chung KS, Song JH, Kim SY, Kim EY, Jung JY, et al. The CReactive Protein/Albumin Ratio as a Predictor of Mortality in Critically Ill Patients. J Clin Med 2018;7:333. 9. Nehring SM, Goyal A, Bansal P, Patel BC. C Reactive Protein (CRP). Treasure Island. FL: StatPearls; 2018. 10. Shalaby M, Di Lorenzo N, Franceschilli L, Perrone F, Angelucci GP, Quareisma S, et al. Outcome of Colorectal Surgery in Elderly Populations. Ann Coloproctol 2016;32:139−43. 11. Prytherch DR, Whiteley MS, Higgins B, Weaver PC, Prout WG, Powell SJ. POSSUM and Portsmouth POSSUM for predicting mortality. Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity. Br J Surg 1998;85:1217−20. 12. Tekkis PP, Poloniecki JD, Thompson MR, Stamatakis JD. Operative mortality in colorectal cancer: prospective national study. BMJ 2003;327:1196−201. 13. Oh TK, Ji E, Na HS, Min B, Jeon YT, Do SH, et al. C-Reactive Protein to Albumin Ratio Predicts 30-Day and 1-Year Mortality in Postoperative Patients after Admission to the Intensive Care Unit. J Clin Med 2018;7:39.

Authors thank Dr. Emre Demir from the Department of Biostatistics for his help with statistical analysis.

14. Wang F, Li P, Li FS. Prognostic role of C-reactive protein to albumin ratio in colorectal cancer: A meta analysis. Medicine (Baltimore) 2019;98:e16064.

Ethics Committee Approval: Approved by the local ethics committee.

15. Yan J, Wang YX, Li ZP. Predictive value of the POSSUM, p-POSSUM, cr-POSSUM, APACHE II and ACPGBI scoring systems in colorectal cancer resection. J Int Med Res 2011;39:1464−73.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kolorektal kanserli hastalarda C-reaktif protein ve plazma albumin seviyesinin oranı mortalite ve morbiditeyi göstermede alternatif bir skorlama olabilir mi? Dr. Yeliz Şahiner,1 Dr. Murat Baki Yıldırım2 1 2

Hitit Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Çorum Hitit Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Çoru

AMAÇ: Bu çalışmada, kolorektal kanser nedeniyle ameliyat edilen ve yoğun bakımda takip edilen hastalarda, C-reaktif proteinin plazma albüminine oranının (CRP/ALB), güncel skorlama sistemleri ile karşılaştırılarak, morbidite ve mortaliteyi ön görmedeki sensitivite ve spesifitesini ortaya koymak amaçlanmıştır. GEREÇ VE YÖNTEM: Kliniğimizde 2015–2018 yılları arasında verilerine ulaşılabilen kolorektal kanser nedeniyle ameliyat olan ve yoğun bakımda yatan hastaların verileri geriye dönük incelendi. CRP/ALB, hem gastrointestinal hemde kolorektal cerrahi için hazırlanan, physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) ve kolorektal hastalar için hazırlanan “Association of Coloproctology of Great Britain and Ireland” (ACPGBI-CRC) skorlama sistemlerinin mortalite ve morbidite ön görmedeki başarıları karşılaştırıldı. BULGULAR: Toplam 119 hasta çalışmada değerlendirilmeye alındı. Hastaların dokuzunda mortalite, 38’inde morbidite olduğu görüldü. Morbiditeyi gösteren tek skorlama sistemi olan P-POSSUM ile kıyaslandığında CRP/ALB oranının daha yüksek bir doğrulukla ön görüsü olduğu bulundu. Mortaliteyi göstermede, CRP/ALB değerinin P-POSSUM, CR-POSSUM ve ACPGBI-CRC’ye oranla daha zayıf olduğu tespit edildi. TARTIŞMA: Skorlama sistemleri kolorektal hastalarda morbidite ve mortaliteyi tahmin etmede kullanışlı olsa dahi pratikte çok fazla parametre içerdikleri için kullanımları zordur. Bu çalışmanın sonuçlarına göre, ek maliyet getirmeden hesaplanabilecek CRP/ALB oranının mortalite ve özellikle morbiditeyi tahmin etmede klinisyene yardımcı olabileceğini düşünüyoruz. Anahtar sözcükler: Kolorektal kanser; organ bozukluk skorlamaları; prognoz; ROC eğrisi; yaşlı; yoğun bakım. Ulus Travma Acil Cerrahi Derg 2020;26(4):580-585

doi: 10.14744/tjtes.2020.34412

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ORIGIN A L A R T IC L E

In intra-articular distal humeral fractures: Can combined medial-lateral approach gain better outcomes than olecranon osteotomy? Libiao Wei, M.D.,1

Haitao Xu, M.D.,2

Zhiquan An, M.D.2

Huadong Hospital Affiliated to Fudan University, Shanghai-China

Department of Traumatic Orthopedics Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai-China

ABSTRACT BACKGROUND: This research aimed to evaluate the functional outcomes of intra-articular distal humeral fractures treated through a combined medial-lateral approach and comparing with olecranon osteotomy simultaneously. METHODS: In this study, 62 distal humeral fractures patients were assessed retrospectively. The olecranon osteotomy was used in 30 cases (14 males, 16 females) and combined medial-lateral in 32 cases (15 males, 17 females). The outcomes of function were assessed by the Mayo Elbow Performance Score (MEPS) and the Disabilities of Arm, Shoulder and Hand (DASH) questionnaire score. The follow-up time was 15.4±3.5 months (range 10–24 months) for a combined medial-lateral group and 14.6±2.6 months (range 10–20 months) for olecranon osteotomy. Level of Evidence: Level, retrospective study. RESULTS: The flexion–extension of elbows was 115.3°±16.1° in the combined medial-lateral group, and the olecranon osteotomy group was 110.1°±15.2°. A significant difference was observed between the two groups for flexion–extension of the elbows (p=0.041). Pronation–supination of the forearms had a significant difference (p=0.025) between the combined medial-lateral group (160.6°±7.2°) and the olecranon osteotomy group (154.1°±9.3°). Mean MEPS, DASH, excellent and good rate and complication rate for combined medial-lateral approaches were 88.6±6.9 points, 9.8±6.6 points, 90.6% and 9.4%, respectively. Significant differences were not noted between the two groups for mean MEPS, DASH scores and excellent and good rate (p=0.594, p=0.505, p=0.934, respectively) except complication rate (p=0.005). CONCLUSION: The combined medial-lateral approach is successful approach in the treatment of intra-articular distal humeral fractures (especially type C1 and C2) that provides better outcomes for the motion of the elbow, bleeding volume in surgery and complications than olecranon osteotomy. Keywords: Combined medial-lateral approach; complication; distal humerus; functional outcomes; olecranon osteotomy; surgical approach.

INTRODUCTION The distal humeral fractures take up 1–7% of all fractures and constitute 30% of all elbow fractures. The distal humeral fractures are clinically difficult to manage, especially the intraarticular fracture. The favorite treatment for intra-articular distal humeral fractures is open reduction and internal fixation (ORIF). In the past 20 years, many studies have suggested

that operation provides satisfactory clinical and radiographic effects. Anatomic reconstruction of the articular surface and stable internal fixation are key factors of the excellent functional effects.[1] To have a good anatomic reduction and stable internal fixation, it is essential to gain enough exposure to the articular surface.[2] Many surgical approaches are used in operation to have excellent exposure, which includes olecranon osteotomy, triceps-reflecting anconeus pedicle (TRAP),

Cite this article as: Wei L, Xu H, An Z. In intra-articular distal humeral fractures: can combined medial-lateral approach gain better outcomes than olecranon osteotomy?. Ulus Travma Acil Cerrahi Derg 2020;26:586-592. Address for correspondence: Zhiquan An, M.D. Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233 Shanghai, China Tel: 18930177455 E-mail: zhiquan_an@163.com Ulus Travma Acil Cerrahi Derg 2020;26(4):586-592 DOI: 10.14744/tjtes.2019.69486 Submitted: 08.04.2019 Accepted: 07.12.2019 Online: 24.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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triceps splitting, Bryan-Murrey (triceps reflecting), extensor mechanism-sparing paratricipital posterior approach and combined medial-lateral approach. Olecranon osteotomy approach is still used the most frequently in the operation because of its adequate exposure.[3] However, it also has many disadvantages, such as nonunion, delayed union, heterotrophic ossification and ulnar nerve paralysis.[3,4] The combined medial-lateral approach combines two different approaches, including medial and lateral of the elbow joint, which can provide good exposure of articular surface, avoid the osteotomy and the less complication.[5] The indications and advantages of the combined medial-lateral approach are lack of literature reports, and there is not any comparison about the two surgical techniques in related literature. Therefore, this research aims to evaluate the functional outcomes of intra-articular distal humeral fractures treated through a combined medial-lateral approach and comparing with olecranon osteotomy simultaneously.

MATERIALS AND METHODS In this study, 62 patients who were diagnosed as intra-articular distal humeral fractures by AO/ASIF classification and treated by ORIF were retrospectively evaluated from 2014 to 2017. This research was allowed by the Medical Ethical Committee of the author’s institution and was proceeded according to the ethical standards of the 1964 Declaration

of Helsinki and later amendments. The combined medial-lateral approach was performed in 32 patients and olecranon osteotomy in 30 patients. Sex and age were no tendencies totally according to statistics, and the fracture classification and time from hurt to surgery did not have any tendency, too (all p>0.05) (Table 1). The exclusion criteria were as follows: pathologic fractures, pediatric fractures, functional loss due to other diseases, open fractures, scanty follow-up time and who cannot endure surgery because of other issues. The cause of injury included 15 cases of fall, eight cases of machinery-related trauma, six cases of traffic injury and three cases of sports injury in the combined medial-lateral group, and 14 cases of fall, 10 cases of traffic injury, four cases of machinery-related trauma and two cases of sport injury in olecranon osteotomy group.

Surgical Technique The whole patients were performed in supine or lateral position and tourniquet was utilized. The whole operations were handled under general anesthesia or blockade of the brachial plexus. In the combined medial-lateral group, the patient stayed supine position and the injured arm was put at 90° of abduction on the operating table. The first incision from medial epicondyle to proximal humerus about 7 cm with the elbow flexed about 60° was begun. The distal humeral medial and

Table 1. Data summary of the patients (mean±SD) Parameters

Combined medial-lateral Olecranon osteotomy (n=32) (n=30)

Male/female ratio (no. of patients) Age (year) (range) Time from hurt to surgery (day) Time of surgery (hour) Bleeding volume in surgery (mL)

15/17

14/16

0.987

43.8±17.7 (18–73)

44.1±17.0 (18–70)

0.815

2.9±1.1

2.9±0.9

0.789

2.3±0.6

2.5±0.7

0.833

128.1±34.2

211.3±40.3

0.001

Healing time of fracture (week) (range)

15.3±2.1 (9–21)

14.9±3.5 (9–20)

0.259

Follow-up time (month) (range)

15.4±3.5 (10–24)

14.6±2.6 (10–20)

0.098

AO/ASIF classification (no. of patients) C1

0.797

The gap in the main articular fragments (no. of patients)

0.623

<1 mm

>1 mm

9.4

Complication rate (%)

0.005

P-value <0.05 was indicated a significant difference. SD: Standard deviation; AO/ASIF: Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation.

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anteromedial side was exposed through the incision between the brachial muscle and the medial intermuscular septum. The ulnar nerve was exposed behind the medial intermuscular septum but not isolated. Then, the flexor muscles were dissected partially and turned up distally, leaving a 5 mm strut to be re-sutured in situ after the surgery. With the anterior capsule cut, the front of the trochlea part and medial epicondyle were exposed. Another incision was initiated from the lateral epicondyle to proximal humerus about 8 cm. The space between the posterior triceps, the origins of the extensor carpi radialis longus, the anterior brachioradialis and the anterior distal humeral articular surface were exposed. The interspace between extensor carpi ulnaris and the anconeus was cut, and the articular surface of the humeral capitulum and the lateral humeral trochlea were exposed. Then keeping the elbow flexed about 80°, the biceps brachii and brachialis were loosed anteriorly. The medial articular fragments were reduced to the medial column and fixed with K-wires temporally. Moreover, the small articular fragments were reduced to the main lateral fragments and fixed with K-wires. The main lateral articular fragments were to be reduced to the medial articular fragments of closing to the lateral column and held with K-wires temporarily. The reduction of the articular surface was collated under the direct sight and the C-arm. When the articular fracture fragments were reduced anatomically, a 1.25-mm guidewire was inserted into the humeral trochlea from lateral condyle to medial condyle then checked by C-arm. Articular surface fracture fragments were fixed by a 4.0-mm cannulated screw inserted through the guidewire. If the articular surface of the distal humerus was reduced anatomically, the medial and lateral column could be fixed with two reconstruction plates and some screws. Finally, the dissected flexor muscles were repaired, and the incisions were sutured (Fig. 1). (a)

(b)

(d)

(e)

In the olecranon osteotomy group, the patient was placed in a lateral position with the arm supported over a bolster. Either the prior incision or a straight posterior incision was used. Medial and lateral skin flaps were elevated, with care taken to protect cutaneous nerve branches and keep them within the skin flaps. The ulnar nerve was recognized by the medial border of the triceps, dissected at least 6 cm proximally and distally, and left in an anteriorly transposed position in the subcutaneous tissues. An apex distal, chevron-shaped osteotomy was performed then. The osteotomy was proceeded about 2 cm distal to the tip of the olecranon. An oscillating or fret saw was used to begin the osteotomy. The posterior elbow capsule was dissected, and the distal humeral articular surface was exposed. The distal humeral fractures fragments were reduced then fixed by K-wires temporarily. While reaching the anatomical reduction, the double plates were used to fix the fracture fragments. The fragment of olecranon osteotomy was restored and fixed by using a tension band and two K-wires. The elbow was then put by a full range of motion to assess the safety of fixation. If the fixation was stable enough, the wound was closed.

Postoperative Care Early functional exercise began once the patient’s pain was under control. Indomethacin was advised to prevent possible myositis ossificans for one month. The drainage tube was removed 1–2 days postoperatively. Changing a medical prescription was performed once every two days and taking out stitches time was approximately two weeks postoperatively.

Follow-up Patients were followed up for once everyone and half months in the first three months, then once every three months until the fracture reached union. After fracture got a union, it was (c)

Figure 1. (a) The patient of staying supine position with the arm put at 90° of abduction on the operating table; (b) the main articular fragments fixed with the K-wires temporarily; (c) the C-arm to ensure the reduction of the articular surface; (d) fixing articular surface by the 4.0-mm cannulated screw inserted; (e) fixing the medial and lateral column by using two reconstruction plates and some screws.

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once every six months up to one year. The gaps in the medial and lateral articular fragments were measured by a postoperative standard anteroposterior and lateral radiograph. The Caja scale was used to assess the reduction level of the distal humeral articular surface.[6] The union standard was that the pain was absent, and the fracture lines of the metaphyseal district fragments and articular surface fragments were obscure. In the final follow-up, the functional assessment of the patients was performed in the motion of elbow and forearm, MEPS and DASH questionnaire.

Statistical Analysis All data were analyzed using SPSS V20.0 and recorded by mean±standard deviation (±SD). A p-value <0.05 indicated a significant difference.

RESULTS In this study, the two aspects in mean follow-up time and healing time of fractures did not have significant differences between the two groups, and another significant diﬀerence was not observed for sex, age, time from hurt to surgery, time of surgery and sort of fractures (all p>0.05). However, bleeding volume in surgery between the two groups had a significant difference (p=0.001) (Table 1). (a)

(b)

(e)

(f)

For the lateral and the medial articular fragments, a gap of less than 1 mm was found in 55 cases, including 29 cases for the combined medial-lateral group and 26 cases for the olecranon osteotomy group. A gap of more than 1 mm was detected in seven cases, including three cases for the combined medial-lateral group and four cases for the olecranon osteotomy group. In accordance with the Caja rating system, 28 cases scored 20, four cases scored 15 for the combined medial-lateral group, and 25 cases scored 20, five cases scored 15 for the olecranon osteotomy group. According to statistical software, the results of fracture fragments reduction had not a significant difference between the two groups (p=0.623). The mean flexion–extension motion of the elbow was 115.3°±16.1° (range 80°–145°) in the combined mediallateral group (Fig. 2), and that of the olecranon osteotomy group was 110.1°±15.2° (range 80°–140°) (Fig. 3). A significant difference was found between the two groups concerning flexion–extension motion of the elbows (p=0.041). Moreover, there was a significant difference noted concerning pronation–supination of the forearms (p=0.025). According to the analysis of statistical software, the mean MEPS, DASH and excellent and good rate were no significant differences between the two groups (p=0.594, p=0.505, p=0.934, respectively) (Table 2).

(c)

(d)

(g)

(h)

Figure 2. Preoperative X-rays and CT of the elbow showing the intra-articular distal humeral fracture (a-c); after double plates fixation using the combined medial-lateral approach, in 13 months of follow-up, X-rays showing fracture union (d, e); functional view of the patient (f-h).

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Wei et al. In intra-articular distal humeral fractures: Can combined medial-lateral approach gain better outcomes than olecranon osteotomy? (a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

Figure 3. (a-c) Preoperative X-rays and CT of the elbow showing the intra-articular distal humeral fracture; (d, e) after double plates fixation using olecranon osteotomy, in 10 months of follow-up, X-rays showing fracture union; (f-h) functional view of the patient.

In the combined medial-lateral group, there was one case of traumatic arthritis after three months postoperatively who was relieved by celecoxib. One patient’s incision was infected after three days postoperatively, and it was healed by dressing change and antibiotics. In one case, ulnar nerve paresthesia appeared, and it was relieved by mecobalamin, which is a drug of nerve nutrition. In the olecranon osteotomy group, there

were eight cases of ulnar nerve paresthesia postoperatively, which were resolved by mecobalamin, vitamin B1, vitamin B6 and functional exercise in three months. Infectious wounds were present in three patients, which were healed by dressing change and antibiotics. One patient developed joint stiffness after three months postoperatively, which was solved by elbow adhesiolysis eventually. There was a significant difference

Table 2. Arc of the elbow motion and functional outcomes (mean±SD) Parameters

Combined medial-lateral Olecranon osteotomy (n=32) (n=30)

Flexion–extension of the elbows (range)

115.3±16.1 (80–145)

110.1±15.2 (80–140)

0.041

Pronation–supination of the forearms (range)

160.6±7.2 (140–180)

154.1±9.3 (140–175)

0.025

DASH score

9.8±6.6

10.5±7.0

0.505

MEPS score

88.6±6.9

85.1±5.4

0.594

Excellent, (n)

Good, (n)

Fair, (n)

Poor, (n) Excellent and good rate (%) *

90.6

90.0

0.934

P-value <0.05 was indicated a significant difference. SD: Standard deviation.

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in the complication rate between the two groups (p=0.005) (Table 1), and the olecranon osteotomy group had a higher complication rate.

DISCUSSION What is the best surgical pathway for exposure, reduction and fixation is presently still controversial. In this study, the findings suggest that the combined medial-lateral approach is more excellent than the olecranon osteotomy approach concerning the flexion–extension of the elbows, the pronation– supination of the forearms, bleeding volume in surgery and complication rate (all p<0.05). While MEPS scores and DASH scores were performed, there was no significant difference based on SPSS V20.0 between the two groups (p=0.594, p=0.505, respectively). Olecranon osteotomy can provide the most extensive exposure of the distal humerus. Tak et al.[7] demonstrated that olecranon osteotomy was used in the treatment of 94 cases of intra-articular distal humerus fractures that contained 30 (32%) type C1, 39 (41%) type C2 and 25 (27%) type C3 fractures with a mean follow-up of 24 months. The final follow-up indicated that 82 (92%) patients had a range of motion elbow more than functional range, 80 (90%) patients had the activity level equaling before the injury, and the excellent and good rate was up to 85.4%. Even though the functional outcomes of elbow joint were well enough, the complication related to osteotomy could not be ignored, which included 23 (25.9%) cases prominent olecranon screw, 17 (19.1%) cases painful bursa over the screw head, 29 (32.6%) cases secondary procedure for removal of symptomatic osteotomy fixation and 4 (4.5%) cases delayed union. From the previous and our study, we can see that although olecranon osteotomy could provide enough exposure of articular surface and good effects, the conspicuous complication is still an intractable issue, such as delayed union, nonunion, implant removal and so on. Xie et al.[5] reported that using a combined medial-lateral approach treated 19 patients (4 of C1, 12 of C2, 3 of C3) with follow-up of 15.8±7.9 (range 7–43) months. At the final follow-up, the mean flexion–extension was 113.4°±20.7°, the pronation–supination of the forearms was 158.3°±8.5°, and the mean MEPS score was 93.7±9.1 points, including 13 excellent and six good cases (excellent or good rates 100%). According to postoperative X-rays and the Caja rating system, 16 cases achieved anatomical reduction, 15 cases scored 20, and four cases scored 15 points. X-rays demonstrated that all the fractures were union with a mean healing time of 14.1±3.0 (range 8–20) weeks. Myositis ossificans happened to one patient and periprosthetic fracture also to one (10.5%) among the whole patients. Our results are similar to the report that had great outcomes of the elbow and low complication rate. Although the combined medial-lateral approach is rarely reported in the literature, the effects of the approach are noticeable and excellent in this study. The combined mediUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

al-lateral approach can keep integrality of the elbow extensor and therefore, does not influence the extension power, which can make patients exercise early. Similar to other surgical approaches, the exposed articular surface of the combined medial-lateral approach is limited and the major exposed district is in front of the distal humeral articular surface. In our unpublished anatomic research article, it shows that the combined medial-lateral approach can expose 46.9% of the distal humeral articular surface, which can provide enough exposure to reduce and fix the fracture fragments. This study also has several limitations. Firstly, this is a retrospective study. The data of patients cannot be controlled by us, and the choice of patients is not randomized so that a bias exists that we cannot avoid. Secondly, the number of patients is not very average, and the majority is type C1 and C2, and C3 is few although there were no significant differences totally for sex, age and classification according to statistics (both p>0.05). Thirdly, we cannot compare with subgroups of the distal humerus fractures, such as comminuted, osteoporotic and osteoarthritis fractures. Future studies should comprise homogeneous sub-group types, specific age groups with a similar degree of osteoporotic bone, which can demonstrate more exact results for surgical indications and effects of combined medial-lateral approach and olecranon osteotomy.

Conclusion From the comparison of our study, the combined medial-lateral approach is a successful approach in the treatment of intra-articular distal humerus fractures (especially type C1 and C2) that provides better outcomes for the motion of elbow, bleeding volume in surgery and complications than olecranon osteotomy.

Acknowledgements The authors declare that they have no competing interests, and all authors have confirmed its accuracy. This study is supported by the fund of the hospital-level project (LYZY-0142). Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Conflict of Interest: None declared.

REFERENCES 1. Gupta R, Khanchandani P. Intercondylar fractures of the distal humerus in adults: a critical analysis of 55 cases. Injury 2002;33:511–5. 2. Hausman M, Panozzo A. Treatment of distal humerus fractures in the elderly. Clin Orthop Relat Res 2004;425:55–63. 3. Chen G, Liao Q, Luo W, Li K, Zhao Y, Zhong D. Triceps-sparing versus olecranon osteotomy for ORIF: analysis of 67 cases of intercondylar fractures of the distal humerus. Injury 2011;42:366–70. 4. Li SH, Li ZH, Cai ZD, Zhu YC, Shi YZ, Liou J, et al. Bilateral plate fixa-

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Wei et al. In intra-articular distal humeral fractures: Can combined medial-lateral approach gain better outcomes than olecranon osteotomy? tion for type C distal humerus fractures: experience at a single institution. Int Orthop 2011;35:433−8. 5. Xie X, Qin H, Shen L, Zeng B, An Z. Open reduction and bi-columnar internal fixation of intra-articular distal humerus fractures through a combined medial and lateral approach. Eur J Orthop Surg Traumatol 2014;24:1115–22.

6. Caja VL, Moroni A, Vendemia V, Sábato C, Zinghi G. Surgical treatment of bicondylar fractures of the distal humerus. Injury 1994;25:433–8. 7. Tak SR, Dar GN, Halwai MA, Kangoo KA, Mir BA. Outcome of olecranon osteotomy in the trans-olecranon approach of intra-articular fractures of the distal humerus. Ulus Travma Acil Cerrahi Derg 2009;15:565–70.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İntraartiküler distal humerus kırıklarında: Kombine mediolateral yaklaşım olekranon osteotomisinden daha iyi sonuçlar elde edilmesini sağlayabilir mi? Dr. Libiao Wei,1 Dr. Haitao Xu,2 Dr. Zhiquan An2 1 2

Fudan Üniversitesi Huadong Hastanesi, Şangay-Çin Shanghai Jiao Tong Üniversitesi Altıncı Halk Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Şangay-Çin

AMAÇ: Araştırma, kombine mediolateral yaklaşımla tedavi edilen intraartiküler distal humerus kırıklarının fonksiyonel sonuçlarını değerlendirmeyi ve eş zamanlı olarak olekranon osteotomisi ile karşılaştırmayı amaçlamaktadır. GEREÇ VE YÖNTEM: Altmış iki distal humerus kırığı geriye dönük olarak incelendi. Otuz olguda (14 erkek, 16 kadın) olekranon osteotomisi ve 32 olguda kombine mediolateral (15 erkek, 17 kadın) yaklaşım kullanıldı. Fonksiyonel sonuçlar Mayo Dirsek Performans Skoru (Mayo Elbow Performance Score: MEPS) ve Kol, Omuz ve El Sakatlıkları (Disabilities of Arm, Shoulder and Hand: DASH) anket skoru ile değerlendirildi. Takip süreleri kombine mediolateral yaklaşım grubu için 15.4±3.5 ay (10–24 ay) ve olekranon osteotomisi için ise 14.6±2.6 ay (10–20 ay) idi. BULGULAR: Dirseklerin fleksiyon-ekstansiyonu kombine mediolateral grupta 115.3°±16.1° ve olekranon osteotomisi grubunda 110.1°±15.2° idi. Dirseklerin fleksiyon-ekstansiyonu açısından iki grup arasında anlamlı bir fark gözlendi (p=0.041). Önkolların pronasyon-supinasyonu açısından kombine mediolateral grup (160.6°±7.2°) ile olekranon osteotomisi grubu (154.1°±9.3°) arasında anlamlı bir fark gözlenmedi (p=0.025). Kombine mediolateral yaklaşımlar için ortalama MEPS, DASH skorlarına göre mükemmel -iyi sonuç puanları ve komplikasyon oranları sırasıyla 88.6±6.9 puana karşın 9.8±6.6 puan ve %90.6’ya karşın %9.4 idi. İki grup arasında komplikasyon oranı (p=0.005) dışında ortalama MEPS, DASH skorları ve mükemmel ve iyi oranlar (sırasıyla p=0.594, p=0.505, p=0.934) arasında önemli farklılıklar görülmemiştir. TARTIŞMA: Kombine mediolateral yaklaşım, intraartiküler distal humerus kırıklarının (özellikle tip C1 ve C2) tedavisinde dirsek hareketi, ameliyattaki kanama hacmi ve komplikasyonlar açısından olekranon osteotomisine göre daha iyi sonuçlar veren başarılı bir yaklaşımdır. Anahtar sözcükler: Cerrahi yaklaşım; distal humerus; fonksiyonel sonuçlar; kombine mediolateral yaklaşım; komplikasyon; olekranon osteotomisi. Ulus Travma Acil Cerrahi Derg 2020;26(4):586-592

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doi: 10.14744/tjtes.2019.69486

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ORIGIN A L A R T IC L E

The role of the lactate level in determining the risk rates of small bowel resection in incarcerated hernias Mutlu Şahin, M.D.,1 Hakan Buluş, M.D.,1 Alper Yavuz, M.D.,1 Veysel Barış Turhan, M.D.,1 Bülent Öztürk, M.D.,1 Nedim Arda Kılıç, M.D.,1 Münire Babayiğit, M.D.,2 Doğan Öztürk, M.D.1 1

Department of General Surgery, Keçiören Training and Research Hospital, Ankara-Turkey

Department of Anesthesiology and Reanimation, Keçiören Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: An incarcerated hernia is a part of the intestine or abdominal tissue that becomes trapped in the sac of a hernia. An increase in morbidity and mortality occurs after intestinal resections from strangulated hernias. This study aims to examine the markers that may be effective in determining the risk of small bowel resection due to incarcerated hernias. In particular, we aimed to investigate the effect s of blood lactate levels in determining this risk. METHODS: A cross-sectional retrospective study was designed. Patients, whose preoperative diagnosis were reported as incarcerated hernia and had essential information, were included in this study. They were divided into two groups according to whether they had resection or not. Age, gender, hernia type, hernia side, resection material, blood lactate level (BLL), white blood cell (WBC), neutrophil count (NE), lymphocyte count (LY), neutrophil/lymphocyte ratio (NLR), platelet count (PLT), lactate dehydrogenase (LDH), radiologic bowel obstruction sign and comorbidities were evaluated. RESULTS: Sixty-seven patients were included in this study. It was observed that 16 (23.9%) of these patients underwent small intestinal resection, 16 (23.9%) had an omentum resection, while no resection was performed on 35 (52.2%) patients. There was a statistically significant difference regarding radiologically intestinal obstruction (p=0.001), hernia type (p=0.005), BLL (p<0.001), WBC, NLR and LDH values (p<0.05). In incarcerated hernia patients with a lactate value ≥1.46 mg/dL, sensitivity was observed to be 84.0% and specificity 86.0% (p<0.001). CONCLUSION: In patients with a preliminary diagnosis of an incarcerated hernia, the risk of possible small bowel resection is the most important point in deciding for an operation. The presence of an intestinal obstruction in radiological examinations, and particularly the high levels of WBC, NLR, LDH and BLL, may indicate a necessity for possible small bowel resection. Concerning the risk associated with small bowel resection, blood lactate levels ≥1.46 mg/dL may be alerting. Keywords: Hernia; lactate; small intestine.

INTRODUCTION Hernia repair is one of the most common surgical procedures. Each type of hernia has a risk of developing incarceration, which is an emergency situation. An incarcerated hernia is a part of the intestine or abdominal tissue that becomes trapped in the sac of a hernia. The hernial sac and its contents cannot be reduced to the abdominal cavity (irreducible) with standard maneuvers. The need for small bowel resection in incarcer-

ated hernias occur most frequently in femoral hernias.[1,2] An increase in morbidity and mortality rates has been reported after intestinal resections from strangulated femoral hernias.[3] Many studies have been carried out to determine the parameters, to predict whether there is intestinal necrosis due to incarceration, before deciding on surgery. Unfortunately, no marker has been found to fully identify intestinal necrosis.

Cite this article as: Şahin M, Buluş H, Yavuz A, Turhan VB, Öztürk B, Kılıç NA, et al. The role of the lactate level in determining the risk rates of small bowel resection in incarcerated hernias. Ulus Travma Acil Cerrahi Derg 2020;26:593-599. Address for correspondence: Mutlu Şahin, M.D. Keçiören Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, 06280 Keçiören, Ankara, Turkey Tel: +90 312 - 356 90 00 E-mail: drmutlu@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):593-599 DOI: 10.14744/tjtes.2020.02500 Submitted: 16.04.2020 Accepted: 27.04.2020 Online: 18.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Ĺ&#x17E;ahin et al. The role of the lactate level in determining the risk rates of small bowel resection in incarcerated hernias

Lactate is the end product of anaerobic glycolysis. It is produced even in conditions where oxygen is sufficient in all tissues (skeletal muscle, brain, erythrocytes, kidneys) of the human body. The normal value of plasma lactate concentration is accepted as being 0.5â&#x20AC;&#x201C;1.5 mmol/L.[4] However, in patients with a critical illness, values up to 2 mmol/L can be considered normal.[4] It was first used as a prognostic tool by Broder and Weil[5] in 1964, showing that greater than 4 mmol/L of lactate was associated with poor results in shock patients. Intestinal hypoxia may lead to anaerobic metabolism. More lactate reaches the liver through the portal vein. Intestinal bacteria metabolize glucose and carbohydrate into D-lactate. As D-lactate may be metabolized slowly by human Lactate dehydrogenase (LDH), it contributes to the formation of lactic acidosis.[6] Therefore, if the arterial circulation of the intestinal segment is disturbed in incarcerated hernia, an increase in serum lactate level can be expected. The level of lactate in peripheral blood has been used as a possible marker for acute mesenteric ischemia (AMI).[7] The present study aims to examine the markers that may be effective in determining the risk of small bowel resection due to incarcerated hernias in the literature. In particular, we aimed to investigate the effects of blood lactate levels in determining this risk.

MATERIALS AND METHODS Ethical approval for this study was obtained from the Clinical Research Ethics Committee on 26.02.2020. A cross-sectional, retrospective study was designed by collecting data, examining patient files and computer records. Patients who were operated on between January 2014 and December 2019 at General Surgery Clinic and whose preoperative diagnosis was reported as incarcerated hernia were included in this study. Patients who did not fit the criteria for this study due to a lack of information in data form were excluded from this study. Patients included were primarily divided into two groups as follows: patients who had a resection due to strangulation and patients who did not have a resection but only had a hernia repair. Patients were evaluated based on age, gender, hernia type, hernia side, resection material, blood lactate level (BLL), white blood cell (WBC), neutrophil count (NE), lymphocyte count (LY), neutrophil/lymphocyte ratio (NLR), platelet count (PLT), lactate dehydrogenase (LDH), radiologic bowel obstruction sign and comorbidities. The blood samples for BLL test were taken venously or arterially in the emergency room. We converted the results obtained from venous blood to arterial form with a special formula[8] and used these results.

Statistical Analysis Continuous variables, mean Âą standard deviation, categorical data were expressed as numbers and percentages. In the intergroup analysis of continuous variables, normality analyses 594

were performed using the Kolmogorov-Smirnov Goodness of Fit Test. In the comparative analysis between two groups conforming to the normal distribution of continuous variables, ttest was used, for the comparative evaluations between three groups, the One Way ANOVA Test (Post-hoc: LSD) was used. Intergroup comparisons of variables not suitable for normal distribution were made using the Kruskal Wallis Test (Posthoc: Mann-Whitney U Test). For the comparison of categorical data, Chi-Square Test was used. The ROC Curve Analysis Test was used to determine the diagnostic cut-off values for lactate in patients with incarcerated hernia. Analyzes were performed using the IBM SPSS Package Program version 24.0 (IBM Corporation, Armonk, NY, USA). The level of statistical significance was accepted as being p<0.05.

RESULTS It was observed that over a six-year-period, 438 patients with a pre-diagnosis of incarcerated hernia were operated. Of these 438 patients, only a total of 67 patients who fit the criteria and whose relevant data were able to be obtained were included in this study (Fig. 1). It was observed that 16 (23.9%) of these patients underwent small intestinal resection, 16 (23.9%) patients had an omentum resection, while no resection was performed on 35 (52.2%) patients. Concerning patients with the comorbid disease, it was observed that there was almost no difference between the groups. Additional chronic diseases were detected in seven (43.75%) of 16 patients who underwent small bowel resection and omentum resection, and in 15 (42.85%) of 35 patients who did not undergo any resection. No statistically significant difference was observed between cases with and without resection concerning age, gender and hernia region (p>0.05) (Table 1). In addition, it was observed that a resection due to femoral hernia was performed in nine (69.23%) of 13 patients operated on under emergency conditions. A statistically significant difference was observed (p=0.007) in comparisons made according to the resection status of patients with radiologically intestinal obstruction (Table 1). When the comparative analyses of resected tissue type were performed according to hernia type, 43.8% of the cases with Incarcerated Hernias (n=438)

Is lactate level measured?

No (n=316)

Yes (n=122) Is other data available?

Exluded from the study Yes (n=55) Excluded from the study Yes (n=67) Included in the study

Figure 1. The process of including patients into this study.

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small bowel resection were observed to be inguinal, 25% femoral and 25% incisional hernia. It was found that 50.0% of cases with omentum resection were related to an umbilical

hernia, and 54.3% of cases without resection were related to an inguinal hernia (p=0.005) (Table 2). In patients with radiologically detected intestinal obstruction, a highly statistically

Table 1. Comparison of the diagnostic features of incarcerated hernia cases according to the presence of resection

With resection

Without resection

Total

61.63±14.13

62.51±17.45

62.7±15.93

0.820* 0.159**

Age (years) (Avg±SD) Gender, n (%)

Female

21 (65.6)

17 (48.6)

38 (56.7)

Male

11 (34.4)

18 (51.4)

29 (43.3)

Hernia type, n (%)

Inguinal

8 (25.0)

19 (54.3)

27 (40.3)

Femoral

9 (28.1)

4 (11.4)

13 (19.4)

Umbilical

9 (28.1)

5 (14.3)

14 (20.9)

Incisional

6 (18.8)

7 (20.0)

13 (19.4)

0.057**

Side, n (%)

Right

7 (21.9)

12 (34.3)

19 (28.4)

Left

10 (31.3)

12 (34.3)

22 (32.8)

Without any side

15 (46.9)

11 (31.4)

26 (38.8)

23 (71.9)

13 (37.1)

36 (53.7)

9 (28.1)

22 (62.9)

31 (46.3)

32 (100)

35 (100)

67 (100)

0.371**

Bowel obstruction, n (%)

Present

Not present

Total

0.007**

T Test; **Chi-square Test. SD: Standard deviation.

Table 2. Comparison of the diagnostic features of incarcerated hernia cases. according to the type of resected tissue Age (years) (Avg±SD)

Small bowel resection

Omentum resection

No resection

Total

64.25±13.43

59.00±14.75

62.51±17.45

62.7±15.93

0.635* 0.076**

Gender, n (%)

Female

8 (50.0)

13 (81.3)

17 (48.6)

38 (56.7)

Male

8 (50.0)

3 (18.7)

18 (51.4)

29 (43.3)

Hernia type, n (%)

Inguinal

7 (43.8)

1 (6.3)

19 (54.3)

27 (40.3)

Femoral

4 (25.0)

5 (31.3)

4 (11.4)

13 (19.4)

Umbilical

1 (6.8)

8 (50.0)

5 (14.3)

14 (20.9)

Incisional

4 (25.0)

2 (12.5)

7 (20.0)

13 (19.4)

4 (25.0)

12 (34.3)

19 (28.4)

0.005**

Side, n (%)

Right

3 (18.8)

Left

8 (50.0)

2 (12.5)

12 (34.3)

22 (32.8)

Without any side

5 (31.2)

10 (62.5)

11 (31.4)

26 (38.8)

15 (93.8)

8 (50.0)

13 (37.1)

36 (53.7)

1 (6.3)

8 (50.0)

22 (62.9)

31 (46.3)

16 (100)

35 (100)

67 (100)

0.110**

Bowel obstruction

Yes

Total

0.001**

No Way ANOVA Test, **Chi-square Test. SD: Standard deviation.

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Table 3. Comparison of some of the diagnostic features of the incarcerated hernia cases, according to resection status

Small bowel resection

Omentum resection

No resection

Lactate (mg/dL)

2.17±0.90* 1.695±0.48* 0.98±0.58* <0.001*

White blood cell (10³/µL)

15.65±4.61*

Neutrophil (10³/µL)

12.72±5.12* 8.29±3.21* 6.59±3.06* <0.001*

Neutrophil/lymphocyte ratio

9.84±10.79*

10.34±4.09 9.23±2.90* <0.001** 5.16±3.69 4.64±3.62* 0.031*

Platelet count (10³/µL)

327.12±84.41* 254.86±105.60* 248.17±64.91* 0.006**

Lactate dehydrogenase (IU/L)

274.06±107.65*

254.56±62.09 211.74±52.38* 0.003*

Kruskal Wallis Test (Post hoc: Mann-Whitney U Test), **One Way ANOVA Test (Post hoc: LSD).

Table 4. AUC and cut-off values of lactate as an indicator for incarcerated hernia patients

Diagnostic test

Lactate

ROC curve

Cut-off (mg/dL)

Sensitivity (%)

Specificity (%)

≥1.46

84.00

86.00

PPV

NPV

AUC

95% CI

47.80 52.20 0.86 0.772–0.965 <0.001**

PPV: Positive predictive value; NPV: Negative predictive value; CI: Confidence interval; AUC: Area under the Curve; ROC: Receiver Operating Characteristic curve analysis test.

significant difference was observed in the comparison made according to the type of tissue resected (p=0.001) (Table 2). BLL was found to be highly statistically significant (p<0.001) in cases having undergone small bowel resection (2.17±0.90 mg/dL) and omentum resection (1.695±0.48 mg/dL), when compared to cases without resection (0.98±0.58 mg/dL). Neutrophil and PLT values were also found to be highly statistically significant in those with the small intestine and ROC Curve

1.0

Approximately 10% of the population develops some type of hernia during their lifetime.[9] In the United States, more than 1 million abdominal hernia repairs are performed each year.[10] Almost 75% of all hernias are inguinal with a rightside predominance, approximately 14% are umbilical, nearly 10% of hernias are incisional or ventral and only 3–5% of hernias are femoral.[11,12] Hernia is the second most common cause of small intestinal obstructions, and almost 5% of all patients operated on for this condition, undergo emergency exploration.[1]

Sensitivity

0.6

0.4

0.2

0.4

0.6

0.8

1.0

1 - Specificity Diagonal segments are produced by ties.

Figure 2. ROC curve of the lactate levels in incarcerated hernias.

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In incarcerated hernia patients with a lactate value ≥1.46 mg/ dL, sensitivity was observed to be 84.0%, specificity 86.0%, area under the ROC curve (Fig. 2) ± standard error (AUC ± SE) = 0.86±0.049 (p<0.001) (Table 4).

DISCUSSION

0.8

0.0 0.0

omentum resection, compared to the patients who did not undergo resection (p<0.05). WBC, NLR and LDH values, between those who underwent small intestinal resection and those who were with no resection, were observed to lead to a significant difference (p<0.05) (Table 3).

Currently, there is no medical consensus on a marker which preoperatively demonstrates if urgent bowel resection should be performed on a patient, who has developed an incarcerated hernia. In different research studies on this subject, various parameters have been presented. One of the most important of these is undoubtedly the type of hernia. In incarceration cases secondary to femoral hernia, the rate of urgent small bowel resection requirement due to necroUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Şahin et al. The role of the lactate level in determining the risk rates of small bowel resection in incarcerated hernias

sis is approximately 45% and this is higher than for other types of hernia.[13–15] There was not any statistical significance found between femoral hernia and resection due to incarceration, in this study. However, it was observed that nine of 13 patients (69.23%) underwent resection and four patients (30.76%) underwent small bowel resection. These high rates indicate that the results are similar to other studies. In this study, there was no statistically significant result found in the evaluation made according to the type of hernia and the measurement made according to the presence of resection (Table 1). In femoral and umbilical hernias, it was observed that proportionally more resections were performed. However, there was no statistically significant difference. Regarding resected tissue type, the findings obtained in this study showed that there was a significant difference between hernia type and resected tissue type (Table 2). It was observed that whilst omentum resection was frequently performed on umbilical hernias in emergency surgery, small bowel resection had to be applied more frequently in strangulations that occur through a narrow channel such as femoral and inguinal hernia. Apart from this, there are studies showing that there is an increased risk of small bowel resection in patients who are of female gender,[14–16] are of advanced age (>65),[14,17] have a long duration of incarceration,[15,18–20] presence of bowel obstruction,[15,18,19] and an apparent peritonitis tableux.[15] Unlike in the studies mentioned above, in this study, it was observed that female gender and older age do not increase the risk of bowel resection. There was no difference between the resection applied to the patient, and whether the hernia was on the right or left side of the patient. Due to insufficient data, it was not possible to evaluate the long duration of incarceration. However, in cases of bowel obstruction defined by radiological imaging methods, significant results were obtained, in parallel with the mentioned studies above. It was observed that in 15 of 16 patients requiring small bowel resection, diagnoses of bowel obstruction was made radiologically. When we looked at from the perspective of laboratory diagnostic methods, there are studies that assert that increased WBC count,[15,18–20] increased neutrophil count[15,20] and increased NLR ratio,[18] increase the risk of small bowel resection. In all of these studies, comparisons were made according to whether there was a small bowel resection or not. In this study, the presence of small intestine or omentum resection and the cases without any resection were compared. Xie et al.[18] reported that NLR ratios can serve as a biomarker for the prediction of severity of incarcerated hernias. When the data of our study were evaluated, it was found that there was a significant difference in WBC and NLR ratios, similar to this study. In addition, LDH values were significantly differUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

ent, between patients who underwent small bowel resection and those who did not. However, in patients with omentum resection, WBC, NLR and LDH values had not increased significantly, compared to the non-resection group. In contrast, neutrophil and PLT values were found to be statistically significantly higher in patients with small intestine and omentum resection compared to patients without resection. According to these results, it is possible to say that the increase in WBC, NLR and LDH levels may be the early precursors of small bowel necrosis. Approximately 1300 mmoL of lactate is produced in the human body in a day. A large portion of this lactate (65–70%) is metabolized by the liver and approximately 30–35% by extrahepatic tissues (kidney, heart, skeletal muscle, diaphragm). Human metabolism generally tries to balance the lactate level at below 1.0 mmol/L. However, in cases where oxygen reaching the tissues is insufficient, serum lactate level is found high. This is frequently observed where volume loss due to trauma or bleeding, excessive dehydration, septic shock, severe anemia, and severe hypoxemia has occurred. Another important reason is the increased oxygen need of tissues. These are the situations as hyperthermia, tremors, seizures or extreme exercise. The final important reason may be an insufficient use of oxygen in tissues. Intestinal hypoxia due to incarcerated hernia is a good example of this. D-Lactate level may increase in some clinical conditions, such as decreased colon motility, short bowel syndrome, jejunoileal by-pass, bacterial infections (Lactobacillus).[21] In other words, the increase in lactate level may be a result of the growth of intestinal bacteria due to intestinal obstruction developed after incarceration. In addition, elevated lactate may permit an early suspicion, and thus influence the clinical decision-making with regard to prioritization of surgery in patients with acute mesenteric ischemia.[22] As can be understood here, an increase in blood lactate level (BLL) may be an early stimulating marker, when small bowel arterial nutrition is disrupted. In the literature, to our knowledge, there is no study investigating the lactate level in incarcerated hernias. Thus, this is the first study to investigate lactate values in incarcerated hernias, patients undergoing small bowel or omentum resection. According to the results of this study, lactate levels are higher in patients who underwent small bowel or omentum resection compared to patients without resection. This increase has been observed to be higher especially in patients with small bowel resection. In incarcerated hernia patients, the cut-off value of lactate was determined as ≥ 1.46. Lactate levels above this value may be a warning that small bowel ischemia may be present. The correlation between venous and arterial lactate levels is low. However, if venous lactate levels are normal, arterial lactate amounts are also very likely to be found at normal values. 597

Şahin et al. The role of the lactate level in determining the risk rates of small bowel resection in incarcerated hernias

In cases indicating a need for lactate measurement, a venous blood sample may be an initial preference.[23] In this study, generally preferred lactate measurement was made through venous blood. The formula developed by Mikami et al.[8] was used in the regulation and calculation of the lactate levels obtained from these venous blood samples. With the help of this formula, the sample from venous blood was sufficient and it was not necessary to retake arterial blood to determine lactate values. Arterial lactate level = (-0.259) + Venous lactate level x (0.996). As Kulah et al.[1] have stated, correct timing is very important when deciding to operate because there is an increase in the mortality rates of patients with advanced age and serious additional diseases, after hernia repair. Patients should not be operated on in emergency conditions unless necessary. They should be carefully prepared in the pre-operative period and should be closely monitored during and after the operation. According to the available data, it is decided whether the patient will undertake a vital operation or not. It is appreciated that, the greatest weakness in this study was the low number of patients. Even though 438 patients were actually operated on over a period of six years, the data required for the purpose of this study could only be obtained for 67 patients. Although this appears to have caused some minor imbalances in the groups we created in this study, it is thought that statistically significant results were obtained.

Conclusion In patients with a preliminary diagnosis of an incarcerated hernia, the risk of possible small bowel resection is the most important point in deciding for an operation. It was observed that during preoperative evaluation, the presence of intestinal obstruction in radiological examinations, and particularly the high levels of WBC, NLR, LDH and serum lactate values detected in laboratory tests, may suggest a necessity for possible small bowel resection. Concerning the risks associated with small bowel resection, blood lactate levels ≥1.46 mg/ dL may be alerting. To investigate this subject, prospective randomized studies with large series are needed. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.Ş.; Design: M.Ş., N.A.K.; Supervision: H.B.; Materials: A.Y., V.B.T., B.Ö., D.Ö., M.B.; Data: N.A.K.; Analysis: M.B.; Literature search: M.Ş.; Writing: M.Ş.; Critical revision: H.B. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. 598

REFERENCES 1. Kulah B, Kulacoglu IH, Oruc MT, Duzgun AP, Moran M, Ozmen MM, et al. Presentation and outcome of incarcerated external hernias in adults. Am J Surg 2001;181:101−4. 2. Kurt N, Oncel M, Ozkan Z, Bingul S. Risk and outcome of bowel resection in patients with incarcerated groin hernias: retrospective study. World J Surg 2003;27:741−3. 3. Dahlstrand U, Wollert S, Nordin P, Sandblom G, Gunnarsson U. Emergency femoral hernia repair: a study based on a national register. Ann Surg 2009;249:672−6. 4. Mizock BA, Falk JL. Lactic acidosis in critical illness. Crit Care Med 1992;20:80−93. 5. Broder G., Weil MH. Excess Lactate: An index of reversibility of shock in human patients. Science 1964;143:1457−9. 6. Rixen D, Siegel J. Bench-to-bedside review: oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and posttraumatic shock. Critical Care 2005;9:441–53. 7. Demir IE, Ceyhan GO, Friess H. Beyond lactate: is there a role for serum lactate measurement in diagnosing acute mesenteric ischemia? Digestive Surgery 2012;29:226–35. 8. Mikami A, Ohde S, Deshpande GA, Mochizuki T, Otani N, Ishimatsu S. Can we predict arterial lactate from venous lactate in the ED?. Am J Emerg Med 2013;31:1118−20. 9. Ruhl CE, Everhart JE. Risk factors for inguinal hernia among adults in the US population. Am J Epidemiol 2007;165:1154−61. 10. Fitch MT, Manthey DE. Abdominal hernia reduction. In: Roberts and Hedges’ Clinical Procedures in Emergency Medicine. Roberts JR, Custalow CB, Thomsen TW, editors. 6th ed. Philadelphia: Elsevier Saunders; 2014.p.873−9. 11. Katz DA. Evaluation and management of inguinal and umbilical hernias. Pediatr Ann 2001;30:729−35. 12. Matthews RD, Neumayer L. Inguinal hernia in the 21st century: an evidence-based review. Curr Probl Surg 2008;45:261−312. 13. Gallegos NC, Dawson J, Jarvis M, Hobsley M. Risk of strangulation in groin hernias. Br J Surg 1991;78:1171−3. 14. Alvarez Pérez JA, Baldonedo RF, Bear IG, Solís JA, Alvarez P, Jorge JI. Emergency hernia repairs in elderly patients. Int Surg 2003;88:231−7. 15. Ge BJ, Huang Q, Liu LM, Bian HP, Fan YZ. Risk factors for bowel resection and outcome in patients with incarcerated groin hernias. Hernia 2010;14:259−64. 16. Tatar C, Tüzün İS, Karşıdağ T, Kızılkaya MC, Yılmaz E. Prosthetic Mesh Repair for Incarcerated Inguinal Hernia. Balkan Med J 2016;33:434−40. 17. Atila K, Guler S, Inal A, Sokmen S, Karademir S, Bora S. Prosthetic repair of acutely incarcerated groin hernias: a prospective clinical observational cohort study. Langenbecks Arch Surg 2010;395:563−8. 18. Xie X, Feng S, Tang Z, Chen L, Huang Y, Yang X. Neutrophil-to-Lymphocyte Ratio Predicts the Severity of Incarcerated Groin Hernia. Med Sci Monit 2017;23:5558−63. 19. Koizumi M, Sata N, Kaneda Y, Endo K, Sasanuma H, Sakuma Y, et al. Optimal timeline for emergency surgery in patients with strangulated groin hernias. Hernia 2014;18:845−8. 20. Chen P, Huang L, Yang W, He D, Liu X, Wang Y, et al. Risk factors for bowel resection among patients with incarcerated groin hernias: A metaanalysis. Am J Emerg Med 2020;38:376−83. 21. Zhang DL, Jiang ZW, Jiang J, Cao B, Li JS. D-lactic acidosis secondary to short bowel syndrome. Postgrad Med J 2003;79:110−2. 22. Ambe PC, Kang K, Papadakis M, Zirngibl H. Can the Preoperative

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Şahin et al. The role of the lactate level in determining the risk rates of small bowel resection in incarcerated hernias Serum Lactate Level Predict the Extent of Bowel Ischemia in Patients Presenting to the Emergency Department with Acute Mesenteric Ischemia?. Biomed Res Int 2017;2017:8038796.

23. Bloom B, Pott J, Freund Y, Grundlingh J, Harris T. The agreement between abnormal venous lactate and arterial lactate in the ED: a retrospective chart review. Am J Emerg Med 2014;32:596−600.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İnkarsere hernilerde ince bağırsak rezeksiyonu risk oranlarını saptamada laktat düzeyinin rolü Dr. Mutlu Şahin,1 Dr. Hakan Buluş,1 Dr. Alper Yavuz,1 Dr. Veysel Barış Turhan,1 Dr. Bülent Öztürk,1 Dr. Nedim Arda Kılıç,1 Dr. Münire Babayiğit,2 Dr. Doğan Öztürk1 1 2

Keçiören Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara Keçiören Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Ankara

AMAÇ: İnkarsere fıtık, bağırsakların veya başka bir abdominal dokunun fıtık kesesi içerisinde sıkışması ile oluşur. Boğulmuş fıtıklardan gelen bağırsak rezeksiyonlarından sonra morbidite ve mortalitede bir artış meydana gelir. Bu çalışmanın amacı, inkarsere fıtıklardan dolayı ince bağırsak rezeksiyonu riskini belirlemede etkili olabilecek belirteçleri incelemektir. Bu riski belirlemede, özellikle kan laktat düzeylerinin etkisini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Kesitsel, geriye dönük bir çalışma tasarlandı. Ameliyat öncesi tanısı hapsedilmiş fıtık olarak bildirilen ve gerekli bilgileri olan hastalar çalışmaya dahil edildi. Rezeksiyona sahip olup olmadıklarına göre iki gruba ayrıldı. Yaş, cinsiyet, fıtık tipi, fıtık tarafı, rezeksiyon materyali, kan laktat seviyesi (BLL), beyaz kan hücresi (WBC), nötrofil sayısı (NE), lenfosit sayısı (LY), nötrofil/lenfosit oranı (NLR), trombosit sayısı (PLT), laktat dehidrojenaz (LDH), radyolojik bağırsak tıkanıklığı işareti ve komorbiditeler değerlendirildi. BULGULAR: İlgili verileri elde edilebilen 67 hasta çalışmaya dahil edildi. Bu hastaların 16’sında (%23.9) ince bağırsak rezeksiyonu, 16’sında (%23.9) omentum rezeksiyonu, 35’inde (%52.2) rezeksiyon yapılmadığı görüldü. Radyolojik olarak bağırsak tıkanıklığı (p=0.001), fıtık tipi (p=0.005), BLL (p<0.001), WBC, NLR ve LDH değerleri (p<0.05) arasında istatistiksel olarak anlamlı fark vardı. Laktat değeri ≥1.46 mg/dL olan hapsedilmiş fıtık hastalarında duyarlılık %84.0 ve özgüllük %86.0 olarak gözlendi (p<0.001). TARTIŞMA: İnkarsere fıtık ön tanısı olan hastalarda, olası ince bağırsak rezeksiyonu riski, bir operasyona karar vermede en önemli noktadır. Radyolojik incelemelerde bağırsak tıkanıklığının varlığı ve özellikle yüksek WBC, NLR, LDH ve BLL seviyeleri, olası ince bağırsak rezeksiyonu için bir gerekliliği gösterebilir. İnce bağırsak rezeksiyonu ile ilişkili risk açısından, ≥1.46 mg/dL kan laktat seviyeleri uyarıcı olabilir. Anahtar sözcükler: Fıtık; ince bağırsak; laktat. Ulus Travma Acil Cerrahi Derg 2020;26(4):593-599

doi: 10.14744/tjtes.2020.02500

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ORIGIN A L A R T IC L E

Perioperative outcomes following a hip fracture surgery in elderly patients with heart failure with preserved ejection fraction and heart failure with a mid-range ejection fraction Ahmet Emrah Açan, M.D.,1 Bülent Özlek, M.D.,2 Cem Yalın Kılınç, M.D.,1 Murat Biteker, M.D.,2 Nevres Hürriyet Aydoğan, M.D.1 1

Department of Orthopedics and Traumatology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla-Turkey

Department of Cardiology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla-Turkey

ABSTRACT BACKGROUND: To examine the influence of heart failure (HF) with preserved ejection fraction (HFPEF) and HF with mid-range ejection fraction (HFmrEF) on perioperative cardiac and noncardiac outcomes following hip fracture surgery. METHODS: Data of elderly patients (≥ 65 years) who underwent hip fracture surgery were retrospectively analyzed in this study. Patients with a left ventricular ejection fraction (LVEF) <40% were not included in this study. The definition of preoperative HFPEF (LVEF ≥50%) and HFmrEF (LVEF 40%–49%) was based on clinical documentation of HF in patients’ medical records before surgery. The primary outcomes of this study were perioperative adverse events and mortality. The secondary outcome of interest was the length of stay in the hospital. RESULTS: A total of 328 patients (mean age 79.2±8.7 years, and 57.3% female) were enrolled. Of the study population, 250 (76.2%) patients had no HF, 50 (15.2%) patients had HFPEF, and 28 (8.6%) patients had HFmrEF before surgery. The frequency of perioperative cardiovascular and non-cardiovascular complications was similar to a rate of 7.0%. The mean length of hospital stay was 8.1±5.8 days, and the in-hospital mortality rate was 4.6%. Patients with HFPEF and HFmrEF had a longer length of stay and were more likely to experience perioperative complications and death than the patients without HF. Multivariate analyses showed that the presence of HFPEF and HFmrEF were both associated with increased rates of perioperative complications and mortality. CONCLUSION: Our findings suggest that the presence of HFPEF and HFmrEF may predict perioperative adverse events and mortality in elderly patients undergoing hip fracture surgery. Keywords: HFmrEF; HFPEF; hip fracture; prognosis; surgery.

INTRODUCTION Hip fracture has been associated with multiple comorbidities, including heart failure (HF).[1] The prevalence of hip fracture and HF is predicted to increase with the aging of the population.[2,3] Interestingly, population-based cohort studies and meta-analyses revealed that HF is associated with an increased risk of hip fracture. Thus, hip fracture and HF are two com-

mon major health problems affecting especially older people. [4,5] Although these two diseases are age-related conditions sharing common risk factors, the relationship between complications of hip fractures and HF was not well elucidated. HF is usually categorized into the three groups according to the left ventricular ejection fraction (LVEF): HF with a reduced ejection fraction (HFrEF, LVEF <40%), HF with preserved

Cite this article as: Açan AE, Özlek B, Kılınç CY, Biteker M, Aydoğan NH. Perioperative outcomes following a hip fracture surgery in elderly patients with heart failure with preserved ejection fraction and heart failure with a mid-range ejection fraction. Ulus Travma Acil Cerrahi Derg 2020;26:600-606. Address for correspondence: Ahmet Emrah Açan, M.D. Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Muğla, Turkey Tel: +90 252 - 214 13 26 E-mail: dremrahacan@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):600-606 DOI: 10.14744/tjtes.2020.23946 Submitted: 09.01.2020 Accepted: 02.03.2020 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

600

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Açan et al. Perioperative outcomes in elderly hip fracture patients with HFPEF and HFmrEF

ejection fraction (HFPEF, LVEF ≥50%), or HF with mid-range ejection fraction (HFmrEF, LVEF 40%–49%).[6] Current studies showed that nearly 50% of the population with HF has HFPEF and HFmrEF.[7] While many studies have focused on the incidence and effects of HFrEF in patients undergoing hip fracture surgery, it has not been thoroughly investigated whether HFPEF or HFmrEF are prevalent and predict perioperative complications.[8,9] Patients with HFPEF undergoing noncardiac surgery are at increased risk for cardiovascular complications. [9] However, there is only one study in the literature evaluating perioperative outcomes in hip fracture surgery for patients with HFPEF.[10] In this recently published database study, HFPEF was found to be a significant perioperative risk of adverse events in patients undergoing hip fracture surgery.[10] However, because of the nature of administrative databases, the value and general applicability of this study are limited. HFmrEF is identified as a new category of HF in the 2016 European guidelines.[6] The clinical characteristics, mortality, and morbidity rates in HFmrEF are intermediate to those seen in HFrEF and HFPEF.[11–14] However, to our knowledge, there has been no study focused on the prevalence or prognostic value of HFmrEF in patients with hip fracture. We, therefore, aimed to investigate the prevalence and effects of HFmrEF and HFPEF in a real-world cohort of elderly patients undergoing hip fracture surgery.

MATERIALS AND METHODS Study Participants and Data Collection Approval for this study was granted by the Faculty ethics committee. This is a single-center and retrospective study conducted in the Medical Faculty hospital, which is a tertiary hospital. This study included elderly patients (≥65 years) who underwent surgery for acute hip fracture. The medical records of patients with femoral neck, intertrochanteric, or subtrochanteric hip fracture undergoing surgery (internal fixation, hemiarthroplasty, or total hip arthroplasty) from June 2016 to June 2019 were retrospectively analyzed. The definition of preoperative HFPEF and HFmrEF was based on clinical documentation of HF in patients’ medical records in our hospital before the surgery. However, patients were not included if the medical records and echocardiographic examination reports did not have adequate information about the parameters related to HFPEF and HFmrEF, such as left ventricular hypertrophy, diastolic functions, and LVEF. In our institution, patients were defined as HFmrEF or HFPEF according to current European guidelines; patients who had at least one sign and symptom of heart failure, elevated natriuretic peptide levels, and at least one additional echocardiographic criterion was defined as HFmrEF or HFPEF according to the LVEF; HFmrEF patients had an LVEF of 40%–49%, and HFPEF patients had an LVEF ≥50%.[6] Patients who had an LVEF <40%, patients with prosthetic valves, and patients with congenital heart diseases were excluded from the study. Patients with multiple trauma, and/or accidents, patients treated nonUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

surgically, and patients with missing information on outcome were also excluded from this study. Data for demographic information, including age, gender, comorbid diseases, body mass index, and all medications, were collected. Laboratory data on admission and American Society of Anesthesiologists (ASA) physical status before surgery were recorded.

Study Endpoints The primary study endpoint was perioperative cardiovascular and non-cardiovascular complications and in-hospital mortality. The secondary outcome of interest was the length of stay in the hospital. Cardiovascular complications were defined as an acute coronary syndrome, nonfatal cardiac arrest, severe arrhythmias, acute heart failure, pulmonary embolism, and cardioembolic stroke. Non-cardiovascular complications were lobar pneumonia, delirium, respiratory failure, bacteremia, and acute renal failure.

Statistical Analysis Data were analyzed using SPSS for Windows (version 24; SPSS Inc, Chicago, IL). Comparison of the patients’ characteristics in three groups (patients with HFmrEF, Patients with HFPEF, and patients with no heart failure) was made using the Chi-square test. Multivariate logistic regression analyses were used to identify predictors of perioperative complications and mortality.

RESULTS A total of 430 elderly patients underwent hip fracture surgery in our institution during the study period. Thirty-six were excluded from this study due to missing or incomplete information about preoperative echocardiography and medical records, and 14 patients were excluded from this study due to prosthetic heart valve or multiple trauma. Data of the remaining 380 patients were analyzed, and 52 patients were also excluded from this study due to an LVEF <40%. Therefore, 328 patients (mean age 79.2±8.7 years and 57.3% female) were included in this study. Of the patients, 280 had surgery at 48 hours postadmission and 48 had surgery >48 hours postadmission. The definition of preoperative HFPEF and HFmrEF was based on patients’ medical records in 182 patients. However, 98 of the patients had a new diagnosis of HFPEF or HFmrEF after preoperative echocardiography. Time to surgery for patients who underwent preoperative echocardiography was not different from the patients who did not undergo preoperative echocardiography (32.4±12.5 hours vs 33.4±11.9 hours, respectively; p=0.32).

Comparison of the Baseline Demographics and Surgical Characteristics Among participants, 250 (76.2%) patients had no HF, 50 (15.2%) patients had HFPEF and 28 (8.6%) patients had 601

Açan et al. Perioperative outcomes in elderly hip fracture patients with HFPEF and HFmrEF

HFmrEF preoperatively. Comparison of baseline demographic and surgical characteristics of hip fracture patients with HFmrEF, HFPEF and without HF is presented in Table 1. There were no significant differences about the type of fracture, type of surgical procedure, anesthetic techniques, the prevalence of hypertension, chronic kidney disease and, cerebrovascular disease between three groups. However, age, gender, ASA physical status, body mass index and the prevalence of comorbidities were significantly different among groups. Patients with HFmrEF were predominantly (71.4%) male, whereas 70% of the HFPEF patients and 58% of the patients without HF were female. The prevalence of coronary artery disease was highest in HFmrEF patients, but the prevalence of diabetes mellitus and atrial fibrillation was highest in HFPEF patients. Compared to the other two groups, patients with HFPEF were older and had higher body mass indexes.

Comparison of the Outcomes The incidence of perioperative cardiovascular and non-cardiovascular complications was similar to a rate of 7.0%. The mean length of hospital stay was 8.1±5.8 days, and the in-hospital mortality rate was 4.6%. Comparison of perioperative complications, mortality, and length of hospital stay are presented in Table 2. Compared to patients without heart failure, the incidence of perioperative cardiovascular and non-cardiovascular complications, and inhospital mortality rates were higher, and length of hospital stay was longer in patients with HFmrEF and HFPEF. Patients with HFPEF and HFmrEF also had a higher incidence of intensive care unit discharge after surgery. When HFPEF and HFmrEF patients were compared, there were no significant differences between the two groups con-

Table 1. Comparison of the demographic and surgical characteristics of hip fracture patients with HFmrEF, HFPEF and without heart failure

Patients with no HF (n=250)

Patients with HFmrEF (n=28)

Patients with HFPEF (n=50)

p-value

HFmrEF vs. No HF

HFPEF vs. No HF

HFmrEF vs. HFPEF

Age, years

78.9±8.3

77.2±7.5

81.2±9.4

0.001

<0.001

Female sex

145 (58.0)

8 (28.6)

35 (70.0)

<0.001

0.032

<0.001

Body mass index (kg/m2) 28.4±6.9 27.5±5.8 30.4±7.7 ASA physical status

3 (1–5)

4 (1–5)

NS 0.005

0.003 0.012 0.016

Comorbidities

Atrial fibrillation

Hypertension

21 (8.4)

5 (17.9)

19 (38.0)

0.001

<0.001

0.040

195 (78.0)

22 (78.6)

39 (78.0)

Diabetes mellitus

65 (26.0)

8 (28.6)

16 (32.0)

0.023

0.045

Chronic kidney disease

25 (10.0)

3 (10.7)

6 (12.0)

Coronary artery disease

35 (14.0)

15 (53.6)

15 (30.0)

<0.001

0.035

0.013

Cerebrovascular disease

15 (6.0)

3 (10.7)

4 (8.0)

Type of Fracture

Femoral neck

128 (51.2)

13 (46.4)

26 (52.0)

Intertrochanteric

102 (40.8)

13 (46.4)

21 (42.0)

Subtrochanteric

20 (8.0)

2 (7.1)

3 (6.0)

Surgical Procedure

Internal fixation

103 (41.2)

11 (39.3)

24 (48.0)

Hemiarthroplasty

135 (54.0)

15 (53.6)

23 (46.0)

Total hip arthroplasty

12 (4.8)

2 (7.1)

3 (6.0)

Type of anesthesia

General anesthesia

88 (35.2)

10 (35.7)

21 (42.0)

Regional anesthesia

162 (64.8)

18 (64.3)

29 (58.0)

Data were presented as mean±standard deviation, median (minimum–maximum) or number (%). ASA: American Society of Anesthesiologists; HF: Heart failure; HFmrEF: Heart failure with a mid-range ejection fraction; HFPEF: Heart failure with a preserved ejection fraction; NS Non-significant.

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Table 2. Perioperative complications, mortality and length of the in-hospital stay

Patients with no HF (n=250)

Patients with HFmrEF (n=28)

Patients with HFPEF (n=50)

HFPEF vs. No HF

HFmrEF vs. HFPEF

<0.001

0.001

0.010

12 (4.8)

Non-cardiovascular complications

11 (4.4)

4 (14.3)

8 (16.0)

<0.001

Death

5 (2.0)

4 (14.3)

6 (12.0)

<0.001

Discharge to ward Discharge to the intensive care unit

6 (12.0)

HFmrEF vs. No HF

Cardiovascular complications

Length of Stay (days)

5 (17.9)

p-value

7.5±5.3

9.5±8.7

9.6±8.3

0.023

0.032

228 (91.2)

23 (82.1)

40 (80.0)

0.041

0.030

22 (8.8)

5 (17.9)

10 (20.0)

0.012

0.001

Data are presented as mean ± standard deviation or number (%). HF: Heart failure; HFmrEF: Heart failure with a mid-range ejection fraction; HFPEF: Heart failure with a preserved ejection fraction; NS Non-significant.

cerning non-cardiovascular complications, length of stay, or mortality rates. However, patients with HFmrEF were more likely to experience cardiovascular complications compared to the patients with HFPEF (17.9 vs. 12%, respectively; p=0.001).

bacteremia in two patients. Older age, ASA status, diabetes mellitus, HFPEF and HFmrEF were identified as significant predictors of non-cardiovascular complications in multivariate analysis (Table 4).

Predictors of the Outcomes

A total of 15 (4.6%) patients died. Age, ASA status, HFPEF and HFmrEF were predictors of in-hospital mortality in multivariate analysis (Table 5).

Twenty-three patients (7%) had cardiovascular complications following surgery. These complications were acute coronary syndrome in nine patients, acute HF in eight patients, nonfatal cardiac arrest two patients, severe arrhythmias in two patients, pulmonary embolism in two patients, and cardioembolic stroke in one patient. Multivariate analysis showed that increased age, atrial fibrillation, coronary artery disease, HFPEF, HFmREF and preoperative ASA status were independent predictors of perioperative cardiovascular complications (Table 3). Twenty-three patients (7%) had non-cardiovascular complications. The most common complication was delirium in eight patients, followed by acute renal failure in five patients, pneumonia in four patients, respiratory failure in four patients, and

95% Cl

Odds Ratio

95% Cl

Age (per 1 y)

1.768

1.119–3.315

0.003

ASA status

2.453

1.102–5.954

<0.001

Diabetes mellitus

3.245

1.586–4.789

<0.001

HFmrEF

1.326 1.096–3.564 0.023

HFPEF

2.563 1.091–4.654 <0.001

ASA: American Society of Anesthesiologists; HFmrEF: Heart failure with a midrange ejection fraction; HFPEF: Heart failure with a preserved ejection fraction; CI: Confidence interval.

Table 3. Multivariate analysis for the prediction of the perioperative cardiovascular complications Odds Ratio

Table 4. Multivariate analysis for the prediction of perioperative non-cardiovascular complications

Table 5. Multivariate analysis for the prediction mortality

Age (per 1 y)

3.188

2.023–5.034

<0.001

Atrial fibrillation

1.345

1.123–3.435

0.020

Coronary artery disease

2.134

1.185–3.854

0.012

HFmrEF HFPEF ASA status

Odds Ratio

95% Cl

Age (per 1 y)

3.456

1.105–6.256

<0.001

2.567 1.734–4.453 <0.001

ASA status

2.052

1.103–3.786

<0.001

1.867 1.134–2.789 0.001

HFmrEF

1.758 1.035–6.689 0.004

1.568

HFPEF

1.523 1.028–5.361 0.005

1.236–4.675

0.015

ASA: American Society of Anesthesiologists; HFmrEF: Heart failure with a midrange ejection fraction; HFPEF: Heart failure with a preserved ejection fraction; CI: Confidence interval.

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ASA: American Society of Anesthesiologists; HFmrEF: Heart failure with a midrange ejection fraction; HFPEF: Heart failure with a preserved ejection fraction; CI: Confidence interval.

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Açan et al. Perioperative outcomes in elderly hip fracture patients with HFPEF and HFmrEF (a)

(b)

(c)

Older age

Diabetes mellitus

Older age

HFmrEF

HFPEF

Preoperative ASA status

Coranary artery disease

Preoperative ASA status

HFmrEF

HFPEF

Older age

Diabetes mellitus

Preoperative ASA status

HFmrEF

HFPEF

Figure 1. Predictors of the cardiovascular complications (a), non-cardiovascular complications (b), and mortality following hip fracture surgery in individuals aged 65 and older (c).

Increased age was associated with the highest risk for cardiovascular complications (odds ratio 3.19), and mortality (odds ratio 3.46). The presence of diabetes mellitus was associated with the highest risk for non-cardiovascular complications (odds ratio 3.25) (Fig. 1). The odds ratio for HFmrEF was higher than the HFPEF for cardiovascular complications and mortality, while HFPEF had a higher odds ratio than the HFmrEF for the prediction of non-cardiovascular complications.

DISCUSSION To our knowledge, this is the first study in the literature investigating the prevalence and prognostic value of HFPEF and HFmrEF in patients undergoing hip fracture surgery. We found that 15.2% of the elderly patients with hip fractures had HFPEF, and 8.6% of these patients had HFmrEF at presentation. The incidence of perioperative adverse events was higher, and length of hospital stay was prolonged in patients with HFPEF and HFmrEF than that of those without HF. Moreover, compared to patients with HFPEF, patients with HFmrEF were more likely to experience cardiovascular complications following surgery. Previous studies showed that several clinical and laboratory variables, such as advanced age, male gender, higher preoperative natriuretic peptide levels, high preoperative ASA classification, history of HF predict hospital readmission, mortality, and morbidity in patients undergoing hip fracture surgery.[15–19] However, only a few studies specifically investigated the prevalence and effects of HF in patients undergoing surgery for hip fracture, and most of these studies included only patients with HFrEF. In a population-based study, the prevalence of preoperative HF was found in 27% of the 1212 patients undergoing hip surgery.[8] Patients with preoperative HF were older, heavier, and more likely male. They also had a longer length of stay, and higher in-hospital mortality compared to patients without HF.[8] However, this study did not separately analyze patients as HFrEF and HFPEF. In a prospective study, 1050 patients with hip fractures who were aged 65 years or older were included.[20] The prevalence of the congestive HF was 6.1% at the time of the hip fracture 604

and patients with a history of congestive HF were at a 40% higher risk of mortality.[20] The only study in the literature examining the prevalence and effects of HFPEF in hip fracture patients has recently been published.[10] In this study, Bohsali et al.[10] identified patients aged 50 years and older with hip fractures undergoing surgery using the Nationwide Inpatient Sample. Among patients, 1.53% was identified with HFPEF and 1.10% with HFrEF. Compared with patients without HF, patients with HFPEF and HFrEF were more likely to be older and had a higher burden of comorbidities. Patients with HFPEF were more likely to be female, whereas patients with HFrEF were less likely to be females. The results of their study revealed that perioperative risk for the acute coronary syndrome, stroke, and death was comparable and similarly elevated in HFrEF and HFPEF patients.[10] Similar to the study that was conducted by Bohsali et al., our study showed that patients with preoperative HFPEF were older, heavier, more likely to be female, and had a higher burden of comorbidities compared to patients without HF. However, we found no differences in age and body mass index between patients with HFmrEF and patients without HF. Compared to patients without HF, patients with HFmrEF were more likely to be male and had a higher burden of comorbidities, including coronary artery disease and atrial fibrillation. Our study results also showed that the presence of HFPEF and HFmREF were predictors of perioperative cardiovascular and non-cardiovascular complications, mortality, and prolonged length of stay in elderly patients undergoing hip fracture surgery. Interestingly, we found that HFmrEF is a better predictor for cardiovascular complications compared to HFPEF, whereas HFPEF is a better predictor for non-cardiovascular complications compared to HFmrEF. Previous studies showed that perioperative diastolic dysfunction and/or HFPEF was associated with perioperative adverse events and mortality in patients undergoing noncardiac surgery.[21–23] However, to our knowledge, no prior study used LVEF in the stratification of patients with hip fractures who underwent surgery. Due to the aging of the population, the incidence of HFPEF/HFmrEF and hip fracture is growUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Açan et al. Perioperative outcomes in elderly hip fracture patients with HFPEF and HFmrEF

ing in the general population. Theoretically, HFPEF/HFmrEF and osteoporosis/osteoporotic fractures may have common pathophysiological components, such as hyperaldosteronism, up-regulation of cytokines, and increased inflammatory mediators.[24–27] Therefore, the prevalence of HFPEF and HFmrEF may be higher in hip fracture patients than in the general population. Although it may be challenging to identify patients with HFPEF and HFmrEF for anesthesiologists and surgeons, our study showed that preoperative determination of these two conditions is essential for proper perioperative risk stratification. Thus, future larger and prospective studies are needed to verify whether preoperative HFPEF and HFmrEF increase perioperative complications.

Study Limitations The results of the present study are based on a retrospective registry, and we did not have follow-up data after discharge. This study was carried out in a single center and included only elderly patients undergoing surgery for hip fracture, and the definition of HFPEF and HFmrEF in the present study was based on medical records.

Conclusion To our knowledge, the present study is the first study that has analyze the prevalence and impact of HFPEF and HFmrEF in patients undergoing surgery for hip fracture. We found that the prevalence of HFPEF was 15.2%, and the prevalence of HFmrEF was 8.6% in this cohort; and compared to participants without HF, HFmrEF and HFPEF patients with hip fractures had a higher burden of comorbidities, a longer length of hospital stay, and higher rates of perioperative complications. Although preoperative identification of patients with HFPEF and HFmrEF is important in clinical practice, further prospective studies are needed to clarify the prognostic implications of this growing HF population in patients with hip fracture. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.E.A, M.B.; Design: A.E.A, M.B.; Supervision: A.E.A., M.B.; Materials: B.Ö., C.Y.K.; Data: B.Ö.,C.Y.K., M.B.; Analysis: B.Ö., M.B.; Literature search: A.E.A., B.Ö., M.B.; Writing: A.E.A., B.Ö.; Critical revision: N.H.A.

2. Pillai A, Eranki V, Shenoy R, Hadidi M. Age related incidence and early outcomes of hip fractures: a prospective cohort study of 1177 patients. J Orthop Surg Res 2011;6:5. 3. Danielsen R, Thorgeirsson G, Einarsson H, Ólafsson Ö, Aspelund T, Harris TB, et al. Prevalence of heart failure in the elderly and future projections: the AGES-Reykjavík study. Scand Cardiovasc J 2017;51:183−9. 4. Carbone L, Buzková P, Fink HA, Lee JS, Chen Z, Ahmed A, et al. Hip fractures and heart failure: findings from the Cardiovascular Health Study. Eur Heart J 2010;31:77−84. 5. Ge G, Li J, Wang Q. Heart failure and fracture risk: a meta-analysis. Osteoporos Int 2019;30:1903−9. 6. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129−200. 7. Chioncel O, Lainscak M, Seferovic PM, et al. Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC Heart Failure LongTerm Registry. Eur J Heart Fail 2017;19:1574−85. 8. Cullen MW, Gullerud RE, Larson DR, Melton LJ 3rd, Huddleston JM. Impact of heart failure on hip fracture outcomes: a population-based study. J Hosp Med 2011;6:507−12. 9. Norring-Agerskov D, Madsen CM, Bathum L, Pedersen OB, Lauritzen JB, Jørgensen NR, et al. History of cardiovascular disease and cardiovascular biomarkers are associated with 30-day mortality in patients with hip fracture. Osteoporos Int 2019;30:1767−78. 10. Bohsali F, Klimpl D, Baumgartner R, Sieber F, Eid SM. Effect of Heart Failure With Preserved Ejection Fraction on Perioperative Outcomes in Patients Undergoing Hip Fracture Surgery. J Am Acad Orthop Surg. 2019 Jun 26. doi: 10.5435/JAAOS-D-18-00731. [Epub ahead of print] 11. Farré N, Lupon J, Roig E, Gonzalez-Costello J, Vila J, Perez S, et al. Clinical characteristics, one-year change in ejection fraction and long-term outcomes in patients with heart failure with mid-range ejection fraction: a multicentre prospective observational study in Catalonia (Spain). BMJ Open 2017;7:e018719. 12. Kapoor JR, Kapoor R, Ju C, Heidenreich PA, Eapen ZJ, Hernandez AF, et al. Precipitating Clinical Factors, Heart Failure Characterization, and Outcomes in Patients Hospitalized With Heart Failure With Reduced, Borderline, and Preserved Ejection Fraction. JACC Heart Fail 2016;4:464−72. 13. Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T, et al; CHART-2 Investigators. Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study. Eur J Heart Fail 2017;19:1258−69.

Conflict of Interest: None declared.

14. Coles AH, Tisminetzky M, Yarzebski J, Lessard D, Gore JM, Darling CE, et al. Magnitude of and Prognostic Factors Associated With 1-Year Mortality After Hospital Discharge for Acute Decompensated Heart Failure Based on Ejection Fraction Findings. J Am Heart Assoc 2015;4:e002303.

Financial Disclosure: The authors declared that this study has received no financial support.

15. Carpintero P, Caeiro JR, Carpintero R, Morales A, Silva S, Mesa M. Complications of hip fractures: A review. World J Orthop 2014;5:402−11.

REFERENCES 1. Edelmuth SVCL, Sorio GN, Sprovieri FAA, Gali JC, Peron SF. Comorbidities, clinical intercurrences, and factors associated with mortality in elderly patients admitted for a hip fracture. Rev Bras Ortop 2018;53:543−51.

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16. Hu F, Jiang C, Shen J, Tang P, Wang Y. Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury 2012;43:676−85. 17. Khan MA, Hossain FS, Ahmed I, Muthukumar N, Mohsen A. Predictors of early mortality after hip fracture surgery. Int Orthop 2013;37:2119−24. 18. Endo A, Baer HJ, Nagao M, Weaver MJ. Prediction Model of In-Hospital

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Açan et al. Perioperative outcomes in elderly hip fracture patients with HFPEF and HFmrEF Mortality After Hip Fracture Surgery. J Orthop Trauma 2018;32:34−8. 19. Ali AM, Gibbons CE. Predictors of 30-day hospital readmission after hip fracture: a systematic review. Injury 2017;48:243−52. 20. Paksima N, Koval KJ, Aharanoff G, Walsh M, Kubiak EN, Zuckerman JD, et al. Predictors of mortality after hip fracture: a 10-year prospective study. Bull NYU Hosp Jt Dis 2008;66:111−7. 21. Fayad A, Ansari MT, Yang H, Ruddy T, Wells GA. Perioperative Diastolic Dysfunction in Patients Undergoing Noncardiac Surgery Is an Independent Risk Factor for Cardiovascular Events: A Systematic Review and Meta-analysis. Anesthesiology 2016;125:72−91. 22. Toda H, Nakamura K, Nakagawa K, Watanabe A, Miyoshi T, Nishii N, et al. Diastolic Dysfunction Is a Risk of Perioperative Myocardial Injury Assessed by High-Sensitivity Cardiac Troponin T in Elderly Patients Undergoing Non-Cardiac Surgery. Circ J 2018;82:775−82.

23. Lerman BJ, Popat RA, Assimes TL, Heidenreich PA, Wren SM. Association of Left Ventricular Ejection Fraction and Symptoms With Mortality After Elective Noncardiac Surgery Among Patients With Heart Failure. JAMA 2019;321:572−9. 24. Weber KT. Aldosterone in congestive heart failure. N Engl J Med 2001;345:1689−97. 25. Chhokar VS, Sun Y, Bhattacharya SK, Ahokas RA, Myers LK, Xing Z, et al. Hyperparathyroidism and the calcium paradox of aldosteronism. Circulation 2005;111:871−8. 26. Baldini V, Mastropasqua M, Francucci CM, D’Erasmo E. Cardiovascular disease and osteoporosis. J Endocrinol Invest 2005;28:69−72. 27. Wisniacki N, Taylor W, Lye M, Wilding JP. Insulin resistance and inflammatory activation in older patients with systolic and diastolic heart failure. Heart 2005;91:32−7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Korunmuş ejeksiyon fraksiyonu ile kalp yetersizlikli ve sınırda ejeksiyon fraksiyonu ile kalp yetersizlikli yaşlı hastalarda kalça kırığı cerrahisi sonrası perioperatif sonuçlar Dr. Ahmet Emrah Açan,1 Dr. Bülent Özlek,2 Dr. Cem Yalın Kılınç,1 Dr. Murat Biteker,2 Dr. Nevres Hürriyet Aydoğan1 1 2

Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Muğla Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Muğla

AMAÇ: Korunmuş ejeksiyon fraksiyonu (KEF-KY) ile kalp yetersizliğinin (KY) ve sınırda ejeksiyon fraksiyonu (SEF-KY) ile KY’nin kalça kırığı cerrahisini takiben perioperatif kardiyak ve kardiyak olmayan sonuçlar üzerindeki etkisini incelemek. GEREÇ VE YÖNTEM: Kalça kırığı ameliyatı geçiren yaşlı hastaların (≥65 yaş) verileri geriye dönük olarak incelendi. Sol ventrikül ejeksiyon fraksiyonu (SVEF) <%40 olan hastalar çalışmaya dahil edilmedi. Ameliyat öncesi KEF-KY (SVEF ≥%50) ve SEF-KY (SVEF %40–49) tanımı, hastaların ameliyat öncesi tıbbi kayıtlarında KY’nin klinik dokümantasyonuna dayanmaktadır. Çalışmanın birincil sonuçları perioperatif olumsuz olaylar ve mortaliteydi. İlgilenilen ikincil sonuç hastanede kalış süresiydi. BULGULAR: Toplam 328 hasta (ort. yaş 79.2±8.7 yıl ve %57.3 kadın) çalışmaya dahil edildi. Çalışma popülasyonunun 250’sinde (%76.2) KY yoktu, 50’sinde (%15.2) KEF-KY ve 28’inde (% 8.6) SEF-KY vardı. Perioperatif kardiyovasküler ve kardiyovasküler olmayan komplikasyonların sıklığı %7.0 ile benzerdi. Ortalama hastanede kalış süresi 8.1±5.8 gündü ve hastane içi mortalite oranı %4.6 idi. KEF-KY ve SEF-KY hastalarının kalış süresi daha uzundu ve KY olmayan hastalara göre perioperatif komplikasyon ve ölüm yaşama olasılığı daha yüksekti. Çok değişkenli analizler, KEF-KY ve SEF-KY varlığının her ikisinin de artmış perioperatif komplikasyonlar ve mortalite ile ilişkili olduğunu göstermiştir. TARTIŞMA: Çalışmamız, KEF-KY ve SEF-KY varlığının kalça kırığı ameliyatı geçiren yaşlı hastalarda perioperatif olumsuz olayları ve mortaliteyi tahmin edebileceğini göstermiştir. Anahtar sözcükler: Cerrahi; HFmrEF; HFPEF; kalça kırığı; prognoz. Ulus Travma Acil Cerrahi Derg 2020;26(4):600-606

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doi: 10.14744/tjtes.2020.23946

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ORIGIN A L A R T IC L E

Is the preoperative neutrophil-to-lymphocyte ratio a predictive value for postoperative mortality in orthogeriatric patients who underwent proximal femoral nail surgery for pertrochanteric fractures? Emre Anıl Özbek, M.D.,

Tacettin Ayanoğlu, M.D.,

Hacı Ali Olçar, M.D.,

Eyyüp Serdar Yalvaç, M.D.,

Department of Orthopedics and Traumatology, Yozgat City Hospital, Yozgat-Turkey

ABSTRACT BACKGROUND: Hip fractures in the orthogeriatric population are a health problem that causes mortality and morbidity, with an increasing frequency. The present study aims to investigate whether the preoperative neutrophil-to-lymphocyte ratio (NLR) is a predictive value for the postoperative mortality risk in patients who underwent only proximal femoral nail (PFN) surgery due to pertrochanteric fractures (PTF). To our knowledge, there is not any study conducted with a similar population in the litertaure. METHODS: Fifty-five patients who were operated on by two National Board-certified surgeons with the PFN method were included in our retrospective study. The patients were divided into two groups. Group A included the patients who lost their lives within the postoperative first year (n=13), while Group B included the survivors (n=42). Preoperative NLR data, demographic information, duration of hospitalization, postoperative intensive care requirements (ICU) and comorbid diseases of all patients were recorded. RESULTS: In our study with a maximum follow-up period of 27 months, no statistically significant difference was found between the groups concerning age, gender, body mass index, preoperative American Society of Anesthesiologists scores (ASA), types of fractures, ICU requirements, duration of hospitalization (p>0.05). However, the NLR was significantly higher in Group A (p<0.01), with a cut-off value of 5.25, sensitivity of 84.6% and specificity of 78.6%. CONCLUSION: We believe that the preoperative NLR is a predictive variable for orthopedic surgeons in assessing the postoperative mortality risk in orthogeriatric patients who presented to the emergency room due to PTF and were planned to undergo PFN surgery. Keywords: Aged; hip fracture; mortality; neutrophil-to-lymphocyte ratio; proximal femoral nail; risk factor.

INTRODUCTION Hip fractures (HFs) in the orthogeriatric population are a health problem with an increasing prevalence.[1] In the UK, 110,000 cases encounter HFs each year, while the affected patients reach approximately 1.5 million worldwide annually. In 2025, it is estimated that this number will reach 2.6 million patients per year.[2,3] Almost half of the HFs, demonstrating such an increase, consist of extracapsular pertrochanteric fractures (PTF) and need absolute surgical fixation.[4]

Dynamic hip screw (DHS), hemiarthroplasty (HA) and proximal femoral nail (PFN) methods are used in the surgical treatment of PTF, all with almost similar postoperative functional results for the hip.[1,4,5] However, the postoperative complication and mortality risk in the minimally invasive PFN have been reported to be lower than other methods.[1,4] Mortality rates of 7–10% in patients who underwent surgery due to HFs were reported during the first 30 days postoperatively. [2] In addition, the mortality rate during the postoperative first year has been reported to vary between 8.4% and 30%,

Cite this article as: Özbek EA, Ayanoğlu T, Olçar HA, Yalvaç ES. Is the preoperative neutrophil-to-lymphocyte ratio a predictive value for postoperative mortality in orthogeriatric patients who underwent proximal femoral nail surgery for pertrochanteric fractures?. Ulus Travma Acil Cerrahi Derg 2020;26:607-612. Address for correspondence: Emre Anıl Özbek, M.D. Yozgat Şehir Hastanesi, Ortopedi ve Travmatoloji Kliniği, Yozgat, Turkey Tel: +90 354 - 219 00 10 E-mail: anl_ozbek@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):607-612 DOI: 10.14744/tjtes.2020.57375 Submitted: 18.07.2019 Accepted: 14.01.2020 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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whereas the mortality rate during the first three years was 27.6%.[1–4,6] Diabetes mellitus (DM), dementia and heart disease have been reported as the negative predictors of postoperative mortality risk; however, definite predictors have not been identified.[3] Recent studies suggested that blood and serum markers may be used as the predictors of postoperative mortality following HFs.[4,6–13] One of these methods, the preoperative neutrophil-to-lymphocyte ratio (NLR) is used as a predictor for the postoperative mortality risk in emergency abdominal, cardiovascular and oncologic surgeries.[12,13] In addition, several other studies suggested that this method can as well be used as a predictor of postoperative mortality following HFs in the orthogeriatric population.[6–11] In almost all studies in the literature, the study groups consist of a heterogeneous patient population that suffers from femoral neck and pertrochanteric hip fractures under “hip fractures”, which are usually treated using the DHS, HA and PFN methods. However, the postoperative mortality risk in the minimally invasive PFN method is lower compared to more invasive methods, such as HA and DHS.[1,4] In our retrospective study, we took the, “Can the NLR be used as a predictive value for mortality during the postoperative first year in PTF patients treated only with the PFN method?” as our guide. The hypothesis of our study was that the NLR was a predictive marker for the postoperative first year mortality risk in patients treated with the minimally invasive PFN method.

MATERIALS AND METHODS Approval of the Ethics Committee of the Faculty of Medicine at Bozok University was obtained for this study. Informed consent forms were obtained from all patients and our study was conducted in accordance with the Declaration of Helsinki.

Patients Fifty-five patients who presented to the emergency department of our hospital due to PTFs between January 2017 and March 2018 were included in our study. The inclusion criteria were to be over 65 years of age, underwent PFN surgery due to PTF. The exclusion criteria were to have multiple fractures, have pathologic PTFs or a history of ipsilateral or contralateral hip surgery. The patients were divided into two groups; patients who lost their lives in the postoperative first year comprised Group A (n=13) and patients who survived comprised Group B (n=42).

Surgery and Care Anteroposterior (AP) and lateral X-rays of the femur were taken, surgical blood tests were performed and 40 mg/0.4 mL of enoxaparin was administered preoperatively. The frac608

tures were classified according to the Evans-Jensen classification based on the preoperative X-rays.[14] The surgery was performed under spinal anesthesia on all patients who were taken to the operating room as soon as they presented at the emergency service. The surgeries were carried out by two different, National Board certified surgeons and without using a traction table. XRBEST (Xinrong Medical, Zhangjiagang, China) PFNs were used via a minimally invasive approach. On postoperative day 1, AP and Lowenstein lateral X-rays of the femur were taken. All patients who did not require postoperative intensive care were encouraged to walk with full weight-bearing with the aid of a walker. The patients were administered 40 mg/0.4 mL of enoxaparin and compression socks for six weeks. Their sutures were removed on the second postoperative week. The patients were followed up on the 2nd week, 6th week and 3rd, 6th and 12th months. X-rays were taken to evaluate any loss of reduction and union at each follow-up visit.

Data The demographic data, preoperative NLR, body mass index (BMI), comorbid diseases, ASA scores, time from the emergency room to the operating room (ER to OR), postoperative intensive care requirements (ICU) and the duration of hospitalization of all patients were recorded. In addition, the patients who died and had their date of death recorded in the National Death Registry system were identified and noted. These data were evaluated for the comparison of both groups and for the postoperative mortality risk.

Statistical Analysis The SPSS v.11 software (SPSS Inc., Chicago, IL, USA) was used to analyze the data. The descriptive statistics were given as mean, standard deviation, median, number and percentage. Normality of the numerical data was evaluated using the Kolmogorov-Smirnov test, and the Mann-Whitney U test was used for group comparisons. Categorical data were compared using the chi-square or Fisher’s exact test. The ROC curve was utilized in assessing whether the NLR could be used as a marker in predicting mortality. The effects of the NLR on mortality was determined using the Kaplan-Meier analysis. The level of statistical significance was set at p<0.05.

RESULTS A total of 55 patients (29 males, 26 females) aged between 68 and 94 years (mean: 80.76±7.6) who were operated for pertrochanteric hip fractures were included in this study. Thirteen patients died in the first year (Group A), making the overall mortality rate for the postoperative first year 23.6%. The groups had a homogeneous distribution; no statistically significant difference was found between the two groups concerning mean age, gender, BMI, preoperative ASA scores, Evans-Jensen fracture type, time from ER to OR and ICU requirement (p>0.05). The comparison of the demographic Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Özbek et al. Preoperative neutrophil-to-lymphocyte ratio

and clinical data of the groups is summarized in Table 1. The mean follow-up period of the patients in Group B was 18.5 (range: 13 to 27) months, and no loss of reduction, infection or implant failure that necessitated a revision surgery were observed postoperatively.

There was a statistically significant difference between the NLRs of the two groups (Fig. 1) (p<0.01). In the ROC analysis performed to investigate whether the NLR could be used as a predictive marker for the postoperative first year mor-

Neutrophil-to-lymphocyte ratio

No statistically significant correlation was detected between age, gender, BMI, preoperative ASA score and Evans-Jensen fracture type and mortality in the postoperative first year (p>0.05). In addition, no statistically significant correlation was detected between the comorbidities of the patients included in our study (hypertension [n=21], atherosclerosis [n=11], diabetes mellitus [n=8], chronic renal failure [n=8] and cerebrovascular event [n=5]) and mortality (p>0.05). However, there was a statistically significant correlation between the presence of two or more comorbidities and mortality (p<0.05).

40.00

40.00 1

40.00 19

40.00

40.00 Group B

Group A

Figure 1. Comparison of the neutrophil-to-lymphocyte ratio in Group A versus Group B.

tality, the area under the curve was 0.861 (p<0.001; lower bound: 0.761, upper bound: 0.961). When the cut-off value was taken as 5.25, the sensitivity and the specificity of this value for mortality were 84.6% and 78.6% respectively (Fig. 2). According to the ROC curve, when the NLR was divided

Table 1. Demographic and clinical data of the patients Variables

Group A (n=13)

Group B (n=42)

Mean±SD Median Mean±SD Median

Age (years)

83.54±7.3 84.0 79.90±7.6 78.0 0.156

Sex, n (%)

Male

Female

Body mass index (kg/m2)

8 (61.5)

21 (50)

5 (38.5)

21 (50)

0.467

25.47±2.5 25.54 26.94±5.4 25.76 0.620

Body mass index, n (%) Underweight

0 1 (2.4) 0.264

Normal

6 (46.2)

Overweight

7 (53.8)

15 (35.7) 13 (31)

Obese

10 (23.8)

Extremely obese

3 (7.1)

ASA score, n (%)

Time from ER to OR (hours)

8 (61.5) 5 (61.5) 44.8±31.5

24.0

21 (50)

0.537

21 (50) 34.7±20.5

24.0

0.356

ICU requirement, n (%)

Yes

3 (23.1)

11 (26.2)

10 (76.9)

31 (73.8)

0.84±1.9

0.47±0.9

0.979

Duration of hospitalization (days)

5.07± 3.5

4.0

5.69±4.0

5.0

0.611

NLR

10.41±8.7 6.70 3.75±2.3 3.20 <0.001

Time in ICU (days)

0.822

ASA: American Society of Anesthesiologists; ER: Emergency room; ICU: Intensive care unit; NLR: Neutrophil-to-lymphocyte ratio; OR: Operating room; SD: Standard deviation.

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Özbek et al. Preoperative neutrophil-to-lymphocyte ratio

(a)

(b)

ROC Curve

1.0

Survival Functions

1.0

0.8

0.6

Cum Survival

Sensitivity

0.8

0.4

0.6

0.4

0.2

NLO High Normal High-censored Normal-censored

0.0 0.0 0.0

0.2

0.4

0.6

0.8

1.0

.00

1 – Specificity Diagonal segments are produced by ties

100.00

200.00

300.00

400.00

Postoperative mortality

Figure 2. (a) The ROC curve for NLR and (b) the Kaplan-Meier survival analysis.

Survival Functions 1.0

Cum Survival

0.8

0.6

0.4

0.2

NLO >5.25 <5.25 >5.25-censored <5.25-censored

0.0 .00

100.00

200.00

300.00

400.00

Postoperative mortality

Figure 3. The Kaplan-Meier curve showing the effect of high neutrophil-to-lymphocyte ratio on postoperative mortality.

into two groups as ‘high’ (>5.25) and ‘normal’ (<5.25), the postoperative surveillance period had significantly decreased in patients with a high NLR (Fig. 3).

DISCUSSION The prevalence of HFs in the orthogeriatric population has increased threefold from the early 2000s to the present day, with PTFs constituting the majority of these fractures with 55.5%.[15] The mortality rate in the patient population under610

going surgery for PTF may reach 30% at the postoperative first year.[16] However, this rate varies depending on the type of surgery performed; the mortality risk after PFN surgery was reported as 16%.[16,17] Nevertheless, HA, PFN and DHS methods were used heterogeneously in the postoperative first year mortality studies following PTF surgery in the orthogeriatric population and the predictive values for mortality were defined. Our study, on the other hand, was carried out in an orthogeriatric population from two homogeneous groups of patients who underwent PFN surgery due to PTFs and our results suggested that the NLR could be used as a predictor of mortality in the postoperative first year with a cut-off value of 5.25. This cut-off value is similar to the cut-off value from other studies in the literature.[6–11] In their study that included 50 patients who underwent HA, Temiz and Ersozlu reported a cut-off value of 5.34.[12] Forget et al.[6] reported a postoperative NLR cutoff value of 4.9 (sensitivity: 62.9%, specificity: 57.6%) as an outcome of their study that included 237 patients with an intracapsular or extracapsular hip fracture. In our study, the sensitivity for the NLR cut-off value was 84.6% and the specificity was 78.6%. However, we found no other study planned with a similar patient population in our review of the literature. Various patient-related factors have been reported to be correlated with mortality in the postoperative first year, including advanced age, high preoperative ASA score, obesity, comorbid diseases and postoperative intensive care requirement.[18–23] In parallel with the literature, the findings of our study suggested that having two or more comorbidities was a risk factor for mortality in the first year postoperative. On the other hand, no significant correlation was established beUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Özbek et al. Preoperative neutrophil-to-lymphocyte ratio

tween age, preoperative ASA score, postoperative intensive care requirement, obesity and duration of hospitalization and mortality in our study. We concluded that this was due to that our study included two groups with a homogeneous distribution for these variables and other studies related to this subject contained different types of fractures and treatments under ‘hip fracture’ topic. Variables that were not related to patients but possessed a risk for postoperative mortality were the surgical treatment method of the fracture, time from ER to OR and the anesthesia method used during surgery.[16,17,20,21] In their study of 136 patients, Aydin et al.[16] reported that PFN surgery for PTFs caused less mortality compared to HA and allowed patients to return to daily life activities earlier. Ergun at al.[17] stated that the PFN method was a better method than the HA method in terms of postoperative functional results. In our study, all patients were operated with the PFN method and under spinal anesthesia, and our postoperative mortality and complication rates were in parallel with the literature. However, in our study, there was no correlation between the time from ER to OR and mortality, and we concluded that this was due to the nature of the studies from the literature which were carried out with heterogeneous groups.[21] Our study had some limitations. The low number of patients included in our study was one of the major weaknesses. Tha the surgical treatments were performed by two different surgeons was another weakness. However, both of these surgeons were certified by the National Board and both possessed an orthopedic surgery experience of more than five years. Another weakness of our study was the lack of NLR data on the fifth day postoperative contrary to other studies from the literature that reported the NLR as a risk factor for postoperative mortality and included this data.[6,12] The majority of the patients included in these studies were treated with HA and the mean duration of hospitalization was longer than five days. In our study, the mean duration of hospitalization times were 5.07 and 5.69 days for the two groups, thus patients with a hospitalization duration of less than five days were also included in our study. However, the hypothesis of our study was designed to identify the predictive postoperative values for postoperative mortality. Despite these limitations, we believe the NLR data we attained in our study will be one of the preoperative predictive variables for the postoperative mortality risk in orthogeriatric patients who were admitted to the emergency department for PTFs and planned to undergo PFN surgery. Nevertheless, we think that the variables not related to patients will be re-evaluated in line with these predictive values by orthopedic surgeons in multicenter studies with a larger population in the future. Each author certifies that he has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/ Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

licensing arrangements) that may pose a conflict of interest in connection with the submitted article. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.A.Ö.; Design: E.A.Ö.; Supervision: T.A.; Fundings: E.A.Ö.; Materials: H.A.O.; Data: H.A.O.; Analysis: E.S.Y.; Literature search: E.A.Ö.; Writing: E.A.Ö.; Critical revision: T.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Tang P, Hu F, Shen J, Zhang L, Zhang L. Proximal femoral nail antirotation versus hemiarthroplasty: a study for the treatment of intertrochanteric fractures. Injury 2012;43:876–81. 2. Fahy AS, Wong F, Kunasingam K, Neen D, Dockery F, Ajuied A, et al. A review of hip fracture mortality—why and how does such a large proportion of these elderly patients die? Surgical Science 2014;5:227−32. 3. Hu F, Jiang C, Shen J, Tang P, Wang Y. Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury 2012;43:676–85. 4. del Prete F, Nizegorodcew T, Regazzoni P. Quantification of surgical trauma: comparison of conventional and minimally invasive surgical techniques for pertrochanteric fracture surgery based on markers of inflammation (interleukins). J Orthop Traumatol 2012;13:125–30. 5. Esen E, Dur H, Ataoğlu MB, Ayanoğlu T, Turanlı S. Evaluation of proximal femoral nail-antirotation and cemented, bipolar hemiarthroplasty with calcar replacement in treatment of intertrochanteric femoral fractures in terms of mortality and morbidity ratios. Eklem Hastalik Cerrahisi 2017;28:35–40. 6. Forget P, Moreau N, Engel H, Cornu O, Boland B, De Kock M, et al. The neutrophil-to-lymphocyte ratio (NLR) after surgery for hip fracture (HF). Arch Gerontol Geriatr 2015;60:366−71. 7. Mosfeldt M, Pedersen OB, Riis T, Worm HO, Mark Sv, Jørgensen HL, et al. Value of routine blood tests for prediction of mortality risk in hip fracture patients. Acta Orthop 2012;83:31−5. 8. Sedlář M, Kvasnička J, Krška Z, Tománková T, Linhart A. Early and subacute inflammatory response and long-term survival after hip trauma and surgery. Arch Gerontol Geriatr 2015;60:431–6. 9. Sun T, Wang X, Liu Z, Chen X, Zhang J. Plasma concentrations of proand anti-inflammatory cytokines and outcome prediction in elderly hip fracture patients. Injury 2011;42:707–13. 10. Sedlár M, Kudrnová Z, Erhart D, Trca S, Kvasnicka J, Krska Z, et al. Older age and type of surgery predict the early inflammatory response to hip trauma mediated by interleukin-6 (IL-6). Arch Gerontol Geriatr 2010;51:e1−6. 11. Fisher A, Srikusalanukul W, Fisher L, Smith P. The Neutrophil to Lymphocyte Ratio on Admission and Short-Term Outcomes in Orthogeriatric Patients. Int J Med Sci 2016;13:588–602. 12. Temiz A, Ersözlü S. Admission neutrophil-to-lymphocyte ratio and postoperative mortality in elderly patients with hip fracture. Ulus Travma Acil Cerrahi Derg 2019;25:71–4. 13. Forget P, Dillien P, Engel H, Cornu O, De Kock M, Yombi JC. Use of

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Özbek et al. Preoperative neutrophil-to-lymphocyte ratio the neutrophil-to-lymphocyte ratio as a component of a score to predict postoperative mortality after surgery for hip fracture in elderly subjects. BMC Res Notes 2016;9:284. 14. Andersen E, Jørgensen LG, Hededam LT. Evans’ classification of trochanteric fractures: an assessment of the interobserver and intraobserver reliability. Injury 1990;21:377–8. 15. Copuroglu C, Ozcan M, Ciftdemir M, Unver KV, Saridogan K. Frequency of hip fractures admitted to a university hospital for the last ten years. Turkish J Geriatrics 2011;14:199−203. 16. Aydin E, Kurtulus B, Celik B, Okan M. Treatment of intertrochanteric fractures in ambulatory elderly; bipolar hemiarthroplasty or proximal femoral nail? Turkish J Geriatrics 2016;19:42−9. 17. Ergun M, Tolunay T, Bozkurt C, Kilicarslan K, Arslan AK. Comparison of clinical results of bipolar hemiarthroplasty for extracapsular and intracapsular hip fractures. Turkish J Geriatrics 2015;18:293−8. 18. Kilicarslan K, Demirkale I, Cicek H, Mutlu T, Catma MF, Kayaalp C, et al. The mid-term results of partial hip arthroplasty for proximal fe-

mur fractures in elderly patients. [Article in Turkish] Turkish J Geriatrics 2010;13:13−7. 19. Tüzün C, Tıkız C. Hip fractures in elderly and problems during rehabilitation. [Article in Turkish] Turkish J Geriatrics 2006;9:108−16. 20. Sarıcaoğlu F, Akinci SB, Süheyla ATAY, Çağlar Ö, Aypar Ü. The effects of anesthesia techniques on postoperative mortality in elderly geriatric patients operated for femoral fractures. [Article in Turkish] Turkish J Geriatrics 2012;15:434−8. 21. Daşar U. One-year retrospective evaluation of hip fracture patients aged more than 80 years and postoperatively monitored in the intensive care unit. Turkish J Geriatrics 2018;21:81−6. 22. Temizel F, Uckun S, Kuzucuoğlu T, Arslan G, Cevik B. The effects of comorbidities on intensive care admission in elderly patients undergoing hip surgeries. Turkish J Geriatrics 2018;21:109−14. 23. Mutlu T, Daşar U. Hip fracture surgery in patients older than 90 years: Evaluation of factors that affect 30-day mortality in a particularly risky group. Turkish J Geriatrics 2018;21:279−84.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ameliyat öncesi nötrofil-lenfosit oranı pertrokanterik kırık nedeniyle proksimal femoral çivi planlanan ortogeriatrik popülasyon için ameliyat sonrası mortaliteyi belirlemede kullanılabilecek ameliyat öncesi bir değer midir? Dr. Emre Anıl Özbek, Dr. Tacettin Ayanoğlu, Dr. Hacı Ali Olçar, Dr. Eyyüp Serdar Yalvaç Yozgat Şehir Hastanesi, Ortopedi ve Travmatoloji Kliniği, Yozgat

AMAÇ: Ortogeriatrik popülasyonda kalça kırığı mortalite ve morbiditeye neden olan ve giderek sıklığı artan bir sağlık problemidir. Çalışmamızın amacı pertrokanterik kırık nedeniyle sadece proksimal femur çivi (PFÇ) cerrahi yöntemi ile tedavi edilmiş hastalarda; ameliyat öncesi nötrofil-lenfosit oranının (NLO) ameliyat sonrası mortalite riski için preditif bir değer olup olmadığını irdelemektir. Literatürde benzer popülasyonda planmış başka bir çalışma tespit edilememiştir. GEREÇ VE YÖNTEM: Geriye dönük olarak planlanan çalışmamıza ulusal ortopedi kurul sertifikalı iki cerrah tarafından PFÇ yöntemi ile ameliyatı gerçekleştirmiş 55 hasta alındı. Hastalar ameliyat sonrası ilk bir yıl hayatını kaybedenler (Grup A [n=13]) ve hayatta kalanlar (Grup B [n=42]) olarak iki gruba ayrıldı. Tüm hastaların ameliyat öncesi NLO değerleri, demografik bilgileri, hastanede kalış süreleri, ameliyat sonrası yoğun bakım (POYB) ihtiyaçları ve komorbid hastalıkları kayıt altına alındı. BULGULAR: En uzun hasta takip süresi 27 ay olan çalışmamız sonucunda her iki grup arasında; yaş, cinsiyet, vücut kitle indeksi, ameliyat öncesi American Society of Anesthesiologist (ASA) skorları, kırık tipleri, POYB ihtiyaçları, hastanede kalış süreleri ve hastaların acil servis başvurusundan ameliyathaneye alınmasına kadar geçen süre açısından anlamlı fark saptanmadı (p>0.05). Bununla birlikte anlamlı şekilde grup A hastalarında NLO değeri daha yüksek gözlenmiş (p<0.01), kestirim değer 5.25, sensitivitesi %84.6, spesifitesi %78.6 idi. TARTIŞMA: Ameliyat öncesi NLO değerinin ortopedik cerrahlar açısından; pertrokanterik kırık nedeniyle acil servise başvuran ve PFÇ cerrahisi planlanan ortogeriatrik hastaların ameliyat sonrası mortalite riski için prediktif değişkenlerden olacağını düşünmekteyiz. Anahtar sözcükler: Kalça kırığı; mortalite; nötrofil-lenfosit oranı; ortogeriatri; risk faktörleri. Ulus Travma Acil Cerrahi Derg 2020;26(4):607-612

612

doi: 10.14744/tjtes.2020.57375

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ORIGIN A L A R T IC L E

Assessment of computed tomography indications and computed tomography reports for usefulness in clinical presentation at postoperative follow-up of gunshot wound cases Mehmet Akif Üstüner, M.D.,

Mehmet Eryılmaz, M.D.

Deparmant of General Surgery, University of Health Sciences Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: The present study aimed to evaluate the results of lower thoracic tomography (LTT) and upper abdominal tomography (UAT) of the patients who were treated and followed at our tertiary center due to gunshot wounds (GSWs). METHODS: The present research was designed as a retrospective descriptive study. All patients, who were admitted to our clinic due to GSW between January 2016 and April 2020, were retrospectively analyzed. This study included 44 patients who had postoperative lower thoracic and upper abdominal tomography scans. RESULTS: Among the patients, 43 (97.72%) were male, and one (2.27%) patient was female, with a mean age of 27.45 (range: 20–53) years. The mean length of hospital stay was 14.93 (range: 5–38) days. The mean number of tomography scans per patient was 1.65 (1–4), and the mean Injury Severity Score (ISS) was 24.38 (12–43). Among the patients, 31 (70.45%) had a direct GSW from a pistol or a rifle, while 13 (29.5%) sustained secondary injuries from shrapnel emanating from a bomb explosion. Furthermore, 23 (52.27%) patients who were initially operated at another center were clinically observed, while 15 (34.09%) patients were operated for the first time, and six (13.63%) patients had their second operation. LTT scans were obtained due to dyspnea, direct thoracic trauma and in addition to abdominal tomography for follow-up in 25 (56.81%), 13 (29.54%) and six (13.63%) patients, respectively. UAT scans were obtained for postoperative follow-up in 29 (65.90%), preoperative assessment in 12 (27.27%) and assessment of blast trauma in the absence of ,direct abdominal trauma in three (6.81%) patients. The most common finding on LTT was effusion (47.7%). No pathology was observed in 61.36% of the UAT scans, while liver laceration was noted in 20.45%. The total cost of LTT and UAT was almost half that of a total thoracic tomography and a whole abdominal tomography. CONCLUSION: Selective lower thoracic and upper abdominal tomography obtained following a gunshot injury may be used not only to detect pathology but also as an efficacious, fast, reliable and cost-effective imaging method. Keywords: Gunshot wound; lower thoracic tomography; upper abdominal tomography.

INTRODUCTION Technological developments have resulted in increased methods for and quality of tomography imaging. Multidetector angiography and tractography have become more significant in blunt and penetrating injuries.[1,2] GSWs may include blunt and penetrating injuries. Tomography for diagnostic and follow-up purposes are important for early diagnosis and treatment in

GSWs.[3] Upper abdominal tomography, which displays solid organs, and lower thoracic tomography, which reveals findings of pneumothorax, hemothorax, effusion and atelectasis, is important in the management of patients with trauma.[4] LTT and UAT can be used as a more cost-effective, faster and more efficient method compared to whole thoracic and abdominal tomography imaging.

Cite this article as: Üstüner MA, Eryılmaz M. Assessment of computed tomography indications and computed tomography reports for usefulness in clinical presentation at postoperative follow-up of gunshot wound cases. Ulus Travma Acil Cerrahi Derg 2020;26:613-619. Address for correspondence: Mehmet Akif Üstüner, M.D. Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 304 20 00 E-mail: ?dr_ustuner@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):613-619 DOI: 10.14744/tjtes.2020.26862 Submitted: 10.05.2020 Accepted: 17.06.2020 Online: 25.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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Üstüner et al. Assessment of CT indications and CT reports for usefulness in clinical presentation at postoperative follow-up of GSW cases

The present study evaluated the results of postoperative LTT and UAT scans of the patients who were treated and followed at our tertiary center due to GSWs. We aimed to assess CT indications and CT reports for usefulness in clinical presentation.

MATERIALS AND METHODS This study was conducted at our clinic, which is a tertiary reference center for GSWs, and was designed as a retrospective descriptive study. This study retrospectively analyzed the patients who were admitted to the clinic due to GSWs between January 2016 and April 2020. This study included 44 patients with available postoperative lower thoracic and upper abdominal tomography scans. Age, gender, length of hospital stay, location and type of injury, LTT and UAT results, ISS scores, operations performed at first admission center and the present center, and morbidity and mortality data of the patients were recorded. All patients received whole thoracic and whole abdominal tomography scans through the routine administration of an intravenous contrast agent (iopromide, ULTRAVİST 370 mg/ dl, Bayer Türk Kimya San. Ltd. Sti) at a dose of 2 ml/kg. The head, neck, pelvis and extremities were also scanned when necessary. The Injury Severity Score (ISS) was calculated by evaluating six regions of the body according to the degree of injury severity through a review of the patient medical records.

Statistical Analysis Statistical analyses were performed using the IBM SPSS for Windows version 21.0 software. Numerical variables were expressed as mean (minimum-maximum). Categorical variables were expressed as frequency (percentages).

RESULTS Among the patients, 43 (97.72%) patients were male, and one (2.27%) patient was female, with a mean age of 27.45 (range: 20–53) years. When patients were examined by age groups, 35 (79.54%) patients were aged 18–30 years, six (13.3%) patients were aged 31–40 years, two (4.54%) patients were aged 41–50 years, and one (2.27%) patient was aged 51–60 years. The mean length of hospital stay was 14.93 (range: 5–38) days. The mean number of tomography scans per patient was 1.65 (1–4). Postoperative morbidities occurred in a total of 19 (43.18%) patients, as wound site infections in 10 (22.72%), intraabdominal abscesses in six (13.63%), enterocutaneous fistulas in two (4.54%) and biliary leakage in one (2.27%). One patient (2.27%) (no:21), who had a gluteal injury and femoral head fracture, and underwent a protective colostomy, died after sepsis (Table 1). 614

The most common injury was in the abdomen (n=41, 93.18%), which was followed by lower extremities (n=16, 36.36%), thorax (n=13, 29.54%), gluteal region (n=9, 20.45%), face (n= 3 6.81%), back (n=3, 6.81%), upper extremities (n=2, 4.54%) and the flank region (n=1, 2.27%). The type of injury was a direct GSW from a gun or a rifle in 31 (70.45%) patients, while 13 (29.5%) sustained secondary injuries from shrapnel emanating from a bomb explosion (Table 2). LTT scans were obtained due to dyspnea, direct thoracic trauma and in addition to abdominal tomography for followup in 25 (56.81%), 13 (29.54%) and six (13.63%) patients, respectively. UAT scans were obtained in 29 (%65.90) for postoperative follow-up, in 12 (27.27%) for preoperative assessment and in three (6.81%) patients for assessment of blast trauma in the absence of direct abdominal trauma. The most common finding on LTT was effusion (47.7%). No pathology was observed in 61.36% of the UAT scans, while 20.45% revealed liver lacerations. The mean Injury Severity Score (ISS) was 24.38 (12–43) (Table 2). Furthermore, 23 (52.27%) patients who were initially operated at another center were clinically observed, while 15 (34.09%) patients were operated for the first time and six (13.63%) patients had their second operation. The most commonly performed operations were primary repair of the liver (n=9, 20.45%), right hemicolectomy (n=8, 18.18%), colostomy (n=8, 18.8%), primary repair of the diaphragm (n=6, 13.63%) and small bowel resection (n=3, 6.81%). The injury was penetrating the abdomen in 36 (81.81%) of 41 patients with an abdominal injury (Table 2). Table 1. General specifications

Male

97.73

Female

2.27

18–30

79.54

31–40

13.63

41–50

4.54

51–60

2.27

Gender

Age groups (years)

Morbidity

Wound site infection

22.72

Intraabdominal abscess

13.63

Enterocutaneous fistula

4.54

Biliary fistula

Total

2.27

43.18

2.27

Mortality Sepsis Length of hospital stay (mean)

14.93 (5–38) days

Number of tomography scans

1.65 (1–4)

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4 Colostomy None None None None Primary repair of the

None Primary repair of the cecum Primary repair of the liver,

17 22 12 17 17 22 22

27 27

22 17 34

Bomb

GSW

Bomb

GSW

Bomb

GSW

Bomb

Abdomen, femur, tibia

Abdomen, femur

Flank region

Abdomen, rectum

Abdomen, gluteal

Abdomen, face

Abdomen, thorax

Abdomen

Abdomen, thorax

Abdomen + femur

Abdomen, gluteal region

Abdomen, thorax

10 29

11 26

12 24

13 22

14 20

15 29

16 36

17 29

18 29

19 23

None None

41 22

GSW

Gluteal region, femur

Rectum, sacrum

22 25

the colon

resection, primary repair of

cholecystectomy, small bowel

diaphragm

primary repair of the

Splenectomy, thoracotomy,

right nephrectomy

Right hemicolectomy +

insertion (right)

diaphragm, chest tube

primary repair of the

Primary repair of the liver,

liver and diaphragm

the liver, colostomy

21 53

Primary repair of

GSW

Abdomen

None

GSW

Abdomen, back

diaphragm

Primary repair of the

GSW

Abdomen

Colostomy

Bomb

Abdomen, eye

Right hemicolectomy

GSW

Abdomen

Colostomy

GSW

Abdomen

Right hemicolectomy

None

Bomb

back, right leg

Abdomen, gluteal region,

Operation

ISS

Type of Injury

Abdomen, left foot, back

Location of injury

No Age Gender

Table 2. General characteristics of the patients

PCT DAY

Respiratory distress

Thoracic trauma

Respiratory distress

Thoracic trauma

Respiratory distress

Thoracic trauma

Respiratory distress

abdominal tomography

For follow-up with

abdominal tomography

For follow-up with

Respiratory distress

LTT ındications

Normal

Effusion

Atelectasis, effusion

Normal

Empyema, consolidation

Atelectasis, consolidation

atelectasis

Effusion, contusion,

Pneumothorax + effusion

Pneumothorax

Normal

Effusion

Normal

Effusion

Effusion, atelectasis

Consolidation, atelectasis

Effusion, atelectasis

Consolidation

Effusion, atelectasis

LTT results

Blast Trauma Follow-up

Postoperative Follow-up

Preoperative assessment

Postoperative Follow-up

Preoperative assessment

Blast Trauma Follow-up

Preoperative assessment

Postoperative Follow-up

Preoperative assessment

Postoperative Follow-up

Preoperative assessment

UAT indications

Normal

Liver laceration

Normal

collection

Subdiaphragmatic

collection

Subdiaphragmatic

Liver laceration

Normal

Liver laceration

Foreign body in the liver

Liver laceration

Normal

Liver hematoma

UAT results

the anal region

+ colostomy + Vac application to

Cholecystectomy + adhesiolysis

end colostomy, cholecystectomy

Primary repair of the rectum,

Clinical Follow-up

Small bowel and colon resection

Clinical Follow-up

Explorative laparotomy

Colostomy, debridement

debridement, Vac

Cholecystectomy, gluteal

Debridement, Vac

Primary repair of the liver

Ostomy revision

Clinical Follow-up

Drainage of lumbar abscess

Clinical Follow-up

Ileostomy

+ VAC

Gluteal Debridement

Post-CT therapy

Üstüner et al. Assessment of CT indications and CT reports for usefulness in clinical presentation at postoperative follow-up of GSW cases

615

616

27 22 22 17 17

22 22 27 22 27 22 29 29 27

GSW

Bomb

GSW

Abdomen, humerus

Abdomen

Abdomen, thorax

Abdomen, pelvis

Abdomen, thorax

Abdomen, tibia

Abdomen, eye, pelvis

Thorax

Abdomen, femur, tibia

Abdomen, thorax, femur

Abdomen, right arm,

Bomb

Abdomen, gluteal region,

GSW

Abdomen, gluteal region,

22 27

GSW

Abdomen + thorax

Abdomen, thorax, gluteal

region

GSW

Abdomen

femur

Bomb

Abdomen, gluteal region

humerus, femur

GSW

Abdomen, gluteal region

right femur

GSW

Abdomen, thorax, femur

ISS

Type of Injury

Location of injury

None Right hemicolectomy, ileostomy, primary repair of the liver and kidney Chest tube insertion (right), primary repair of liver and kidney

Primary repair of the stomach and diaphragm, splenectomy, tube thoracostomy

Right hemicolectomy

None

Explorative laparotomy

None

Explorative laparotomy

bowel and colon

Primary repair of the small

of the diaphragm

Splenectomy, primary repair

None

Primary repair of the liver

on, primary repair of the liver

Right lung lower lobe resecti-

Thoracic trauma

Respiratory distress

abdominal tomography

For follow-up with

abdominal tomography

For follow-up with

Respiratory distress

Thoracic trauma

Respiratory distress

abdominal tomography

For follow-up with

Thoracic trauma

abdominal tomography

For follow-up with

Thoracic trauma

Respiratory distress

Thoracic trauma

Preoperative assessment

Postoperative Follow-up

Preoperative assessment

Postoperative Follow-up

Hemothorax, atelectasis

consolidation

Effusion, atelectasis,

Atelectasis, consolidation

contusion

Effusion, foreign body,

Normal

effusion

Postoperative Follow-up

Preoperative assessment

Postoperative Follow-up

Preoperative assessment

Atelectasis, consolidation, Postoperative Follow-up

Effusion, contusion

Foreign body, effusion

Pneumothorax, contusion

Effusion

Contusion

Atelectasis

Hemothorax, atelectasis

Atelectasis

contusion

Effusion, atelectasis,

Hemithorax, contusion

Effusion

Primary repair of the kidney, colostomy

mediastinum, consolidation

the liver

Pneumothorax, pneumo-

Consolidation, atelectasis

Thoracic trauma

Respiratory distress

Postoperative Follow-up

UAT indications

consolidation, Postoperative Follow-up

Colostomy, primary repair of

Effusion,

Pneumothorax, effusion

LTT results

Colostomy

Respiratory distress

Thoracic trauma

LTT ındications

infiltration

PCT DAY

primary repair of the liver

Right hemicolectomy,

gastric resection

Chest tube insertion, partial

Operation

GSW: Gunshot wound; LTT: Lower thoracic tomography; UAT: Upper abdominal tomography,; ISS: Injuriy Severity Score; PCT DAY: Postoperative computed tomography scanning day.

No Age Gender

Table 2. General characteristics of the patients (continuation)

Right hemicolectomy

Clinical Follow-up

Wound debridement, VAC

Right hemicolectomy

Wound debridement, VAC

Clinical Follow-up

+ colostomy

matoma

Liver laceration, renal he- Clinical Follow-up

hematoma

Liver laceration + renal Clinical Follow-up

Renal contusion

Normal

Liver calcification

Normal

collection

Subdiaphragmatic

Small bowel and colon resection

(Bile leakage)

Normal

ERCP/Nasobiliary drainage

hematoma

Clinical Follow-up

Post-CT therapy

Liver laceration,

of the liver

hematoma and laceration

Pseudoaneurysm,

Normal

UAT results

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The total cost of LTT and UAT was almost half that of a total thoracic tomography and a whole abdominal tomography (63 TL & 120 TL).

DISCUSSION The present study assessed perioperative LTT and UAT scans that were performed on patients admitted to our clinic following GSWs. LTT was requested due to respiratory distress in 56.81%, due to thoracic trauma in 29.54% and for a follow-up examination in addition to abdominal tomography in 13.63% patients. UAT was performed in 65.90% for postoperative follow-up, in 27.27% for preoperative assessment and in 6.81% of patients for assessment of the blast trauma in the absence of a direct abdominal trauma. The most common LTT finding was effusion (47.7%). No pathology was observed in 61.36% of UAT scans, while 20.45% revealed liver lacerations. The total cost of LTT and UAT was almost half that of a total thoracic tomography and a whole abdominal tomography. An average of 80,000 non-fatal and 30,000 fatal GSWs occur in the United States every year.[5] As a type of trauma, GSW is different from regular traumas by nature. The injuries sustained from GSWs are related to the speed and energy of the bullet, and there is also a blast effect. Bullets spin when they enter into the body, leading to more damage than expected. As such, the initial physical findings may be misleading.[6] GSWs are associated with a high mortality rate and account for 90% of all penetrating traumas.[7] The mortality rate in the present study was 2.27%, which is lower than reported by previous studies in the literature. Mortalities occurring at the scene and at the first admission center were not considered. GSWs result in indefinite numbers of deeper penetrations and more tissue loss. It is reported in the literature that approximately 80% of such wounds penetrate into the peritoneal cavity.[8] The rate was 81.81% in the present study, which is consistent with the literature. The most frequently injured abdominal organs following GSWs are reported to be, in descending order, the small bowel, colon and liver.[7] Such order was different in the present study, with the most frequently injured organs being, in descending order, the liver, colon, diaphragm and small bowel. The study conducted by Meral et al.[9] reported that 85.4% of patients with GSWs were male, and 49.8% were aged 18–30 years. In the present study, 97.72% of the cases were male, and 79.54% were aged 18–30 years. The study by Turan et al.[10] demonstrated that the ISS value (>20) after GSWs was a factor with an effect on mortality, but it was not an independent risk factor alone. In the present study, the mean ISS value was 24.38 (12–43) and was 41 in a single patient who died. GSWs account for approximately 3.2% of all trauma cases, with a mortality rate of 10% according to 2019 data (Spring 2019 Trauma Quality Improvement Program report) on 300,000 patients.[11] A direct exploratory laparotomy is indicated if Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

there is hemodynamic instability, peritonitis, evisceration, hematemesis and gross blood loss through the rectum after an abdominal GSW, according to the Western Trauma Association’s algorithm. If none of the above is present, bedside FAST imaging and direct X-rays (abdominal/pelvic/chest X-rays) are performed. An exploratory laparotomy is also indicated in the presence of high-volume fluid in multiple intraperitoneal quadrants, free intraabdominal air or multiple abdominal GSWs. If none of the above is present and the abdominal examination is suspicious, an exploratory laparotomy can also be performed or a tomography scan can be obtained to determine the site of injury and also for preoperative surgical planning. If the patient is not operated and “Selective Nonoperative Management” is applied, then serial tomography scans are acquired at follow-up.[12] Tomography after GSWs provides information on the site and size of the trauma in a 3D imaging quality. The sensitivity and specificity of tomography after an intraabdominal injury are 90.5% and 96%, respectively.[13] The sensitivity and specificity of abdominal tomography with triple (oral + IV + rectal) contrast enhancement after GSWs is 100% and 96–100%, respectively.[14–16] Thoracic tomography is helpful in assessing lungs, vertebrae and diaphragm, and diagnosing pulmonary embolism among patients with trauma. Direct chest X-rays have been assessed as totally normal in a considerable number of patients (14– 65%) despite the presence of a significant injury. Therefore, the use of thoracic tomography in selected patients has led to a substantial change (18–41%) in patient management.[17] The mediastinum is also evaluated using thoracic tomography in GSW cases. A prospective study observed mediastinal injuries requiring no further assessment on thoracic tomography in 67% of the cases following GSW.[18] Diaphragmatic lacerations can be detected at a rate of 60–90% when the coronal and sagittal sections are simultaneously assessed.[19,20] There is a tendency to perform a whole-body computed tomography (WBCT) in emergency departments where the first intervention is provided in GSWs, as with other trauma cases. However, contrast-induced nephropathy and radiation exposure should not be ignored along with its potential benefits. [21,22] The lifetime cancer-related mortality rate after wholebody tomography is 0.08%, which increases up to 2% with annual scans.[23–26] The estimated lifetime cancer risk from angiographic tomography of the coronary arteries and aorta is 0.87% for a 20-year-old woman and 0.15% for a 20-yearold man.[23] WBCT aims to reduce mortality without missing out potential injuries. Nevertheless, previous meta-analyses have demonstrated no effect of WBCT on mortality.[27,28] In this regard, the randomized controlled study by Sierink et al.,[3] which was conducted with multicenter trauma centers (REACT-2) reported that WBCT did not reduce hospital-related mortality, and recommended selective tomography. In conclusion, there is currently a tendency towards selective tomography rather than WBCT for patients with trauma. 617

Üstüner et al. Assessment of CT indications and CT reports for usefulness in clinical presentation at postoperative follow-up of GSW cases

Similarly, targeted lower thoracic and upper abdominal tomography can be performed rather than whole thoracic and abdominal tomography scans. Findings, such as pneumothorax, hemothorax, effusion, consolidation and atelectasis, can only be identified by lower thoracic tomography and especially on follow-up scans after GSWs. Likewise, a follow-up assessment of solid organs, such as the liver, kidneys and pancreas, can be performed, and intraabdominal fluid and subdiaphragmatic air can be identified only by upper abdominal tomography. Thus, patients with GSWs are protected both from nephropathy and unnecessary radiation, with a further advantage of lower cost. The review of literature revealed no previous research on this matter. Thus, to our knowledge, the present study is the first in this regard.

Limitations The limitations of the present study were its single-center and retrospective design. Multi-center, prospective studies with a longer follow-up duration are needed.

Conclusion Selective lower thoracic and upper abdominal tomography scans following gunshot wounds may be used to not only detect pathologies but also as an efficient, fast, reliable and costeffective imaging method at postoperative follow-up. Ethics Committee Approval: Ethics committee approval was obtained from the SBU Gulhane T & R Hospital for this study (Date: 19.05.2020, No:2020-215). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.E., M.A.Ü.; Design: M.E., M.A.Ü.; Supervision: M.E.; Materials: M.A.Ü.; Data: M.A.Ü.; Analysis: M.E.; Literature search: M.A.Ü.; Writing: M.E., M.A.Ü.; Critical revision: M.E. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Akkoca M, Balas S, Yilmaz KB, Tatar IG, Akinci M, Tokgoz S, et al. CT-guided tractography is a safe and complementary diagnostic tool in the management of penetrating abdominal trauma. Asian J Surg 2019;42:148−54. 2. Pieroni S, Foster BR, Anderson SW, Kertesz JL, Rhea JT, Soto JA. Use of 64-row multidetector CT angiography in blunt and penetrating trauma of the upper and lower extremities. Radiographics 2009;29:863−76. 3. Sierink JC, Treskes K, Edwards MJ, Beuker BJ, den Hartog D, Hohmann J, et al; REACT-2 study group. Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial. Lancet 2016;388:673−83. 4. Ye B, Miao YD. Acute liver failure secondary to hepatic compartment syndrome: Case report and literature review. Ulus Travma Acil Cerrahi Derg 2014;20:136–8.

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5. Dreizin D, Munera F. Multidetector CT for penetrating torso trauma: state of the art. Radiology 2015;277:338–55. 6. Karaca MA, Kartal ND, Erbil B, Öztürk E, Kunt MM, Şahin TT, et al. Evaluation of gunshot wounds in the emergency department. Ulus Travma Acil Cerrahi Derg 2015;21:248−55. 7. Nicholas JM, Rix EP, Easley KA, Feliciano DV, Cava RA, Ingram WL, et al. Changing patterns in the management of penetrating abdominal trauma: the more things change, the more they stay the same. J Trauma 2003;55:1095−10. 8. Pryor JP, Reilly PM, Dabrowski GP, Grossman MD, Schwab CW. Nonoperative management of abdominal gunshot wounds. Ann Emerg Med 2004;43:344−53. 9. Meral O, Sağlam C, Güllüpınar B, Aktürk ÖE, Beden S, Parlak İ. Investigation of firearm injury cases presented to training and research hospital’s emergency service. Bir eğitim ve araştırma hastanesi acil servisine başvuran ateşli silah yaralanması olgularının incelenmesi. Ulus Travma Acil Cerrahi Derg 2020;26:74−9. 10. Turan O, Eryilmaz M, Albuz O. The correlation between Injury Severity Score, vital signs, and hemogram values on mortality in firearm injuries. Ulus Travma Acil Cerrahi Derg 2019;25:259−67. 11. American College of Surgeons. Trauma Quality Improvement Program (TQIP) Benchmark Report. Committee on Trauma; Spring: 2019.p.1– 44. 12. Martin MJ, Brown CVR, Shatz DV, Alam H, Brasel K, Hauser CJ, et al. Evaluation and management of abdominal gunshot wounds: A Western Trauma Association critical decisions algorithm. J Trauma Acute Care Surg 2019;87:1220−7. 13. Elmahrouky A, Selim MA, Elward AS, Balamoun HA, Mohiy HH. Conservative management versus surgical intervention for penetrating abdominal shotgun injuries. Int Surg J 2019;6:3480−6. 14. Pham TN, Heinberg E, Cuschieri J, Bulger EM, O’Keefe GE, Gross JA, et al. The evolution of the diagnostic work-up for stab wounds to the back and flank. Injury 2009;40:48−53. 15. Albrecht RM, Vigil A, Schermer CR, Demarest GB 3rd, Davis VH, Fry DE. Stab wounds to the back/flank in hemodynamically stable patients: evaluation using triple-contrast computed tomography. Am Surg 1999;65:683−8. 16. Hauser CJ, Huprich JE, Bosco P, Gibbons L, Mansour AY, Weiss AR. Triple-contrast computed tomography in the evaluation of penetrating posterior abdominal injuries. Arch Surg 1987;122:1112−5. 17. Plurad DS, Rhee P. The role of chest computed tomography in trauma. Journal of trauma 2008;10:219−30. 18. Hanpeter DE, Demetriades D, Asensio JA, Berne TV, Velmahos G, Murray J. Helical computed tomographic scan in the evaluation of mediastinal gunshot wounds. J Trauma 2000;49:689−95. 19. Killeen KL, Mirvis SE, Shanmuganathan K. Helical CT of diaphragmatic rupture caused by blunt trauma. AJR Am J Roentgenol 1999;173:1611−6. 20. Bergin D, Ennis R, Keogh C, Fenlon HM, Murray JG. The “dependent viscera” sign in CT diagnosis of blunt traumatic diaphragmatic rupture. AJR Am J Roentgenol 2001;177:1137−40. 21. Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328−34. 22. Birck R, Krzossok S, Markowetz F, Schnülle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598−603. 23. Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography

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Üstüner et al. Assessment of CT indications and CT reports for usefulness in clinical presentation at postoperative follow-up of GSW cases coronary angiography. JAMA 2007;298:317−23. 24. Rice HE, Frush DP, Farmer D, Waldhausen JH; APSA Education Committee. Review of radiation risks from computed tomography: essentials for the pediatric surgeon. J Pediatr Surg 2007;42:603−7. 25. Brenner DJ, Elliston CD. Estimated radiation risks potentially associated with full-body CT screening. Radiology 2004;232:735−8. 26. Semelka RC, Armao DM, Elias J Jr, Huda W. Imaging strategies to reduce the risk of radiation in CT studies, including selective substitution

with MRI. J Magn Reson Imaging 2007;25:900−9. 27. Sierink JC, Saltzherr TP, Reitsma JB, Van Delden OM, Luitse JS, Goslings JC. Systematic review and meta-analysis of immediate totalbody computed tomography compared with selective radiological imaging of injured patients. Br J Surg 2012;99:52−8. 28. Healy DA, Hegarty A, Feeley I, Clarke-Moloney M, Grace PA, Walsh SR. Systematic review and meta-analysis of routine total body CT compared with selective CT in trauma patients. Emerg Med J 2014;31:101−8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ateşli silah yaralanması olgularının ameliyat sonrası takibinde bilgisayarlı tomografi endikasyonları ve bilgisayarlı tomografi raporlarının kliniğe yararlılığı açısından değerlendirilmesi Dr. Mehmet Akif Üstüner, Dr. Mehmet Eryılmaz Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Ankara

AMAÇ: Çalışmamızda ateşli silah yaralanmaları (ASY) nedeniyle tersiyer merkezimizde takip ve tedavisi yapılan hastaların alt toraks tomografisi (ATT) ve üst batın tomografi (ÜBT) sonuçlarının değerlendirilmesi amaçlandı. GEREÇ VE YÖNTEM: Çalışmamız geriye dönük tanımlayıcı bir çalışma olarak planlandı. Ocak 2016–Nisan 2020 tarihleri arasında ASY nedeniyle kliniğimizde yatışı yapılan hastalar geriye dönük olarak analiz edildi. Ameliyat sonrası alt toraks ve üst batın tomografileri çekilen 44 hasta değerlendirmeye alındı. BULGULAR: Hastaların 43’ü (%97.72) erkek 1’i (%2.27) kadın, yaş ortalaması 27.45 (dağılım, 20–53) idi. Hastanede kalış süreleri ortalama 14.93 (dağılım, 5–38) gündü. Çekilen tomografi sayısı ortalama 1.65 (dağılım, 1–4) olup Injuriy Severity Score (ISS) ortalama 24.38 (dağılım, 12–43) idi. Hastaların 31’i (%70.45) tabanca ya da tüfek gibi doğrudan ASY’ye maruz kalırken, 13’ü (%29.5) bomba patlaması sonucu ortama dağılan şarapnel parçaları ile sekonder olarak yaralandı. İlk operasyonları dış merkezde yapılan 23 (%52.27) hastaya klinik izlem yapıldı, 15 (%34.09) hasta ilk kez ameliyat edildi, 6 (%13.63) hasta ise 2. kez ameliyat edildi. ATT; 25 (%56.81) hastada solunum sıkıntısı nedeniyle,13 (%29.54) hastada dogrudan toraks travması nedeniyle, 6 (%13.63) hastada ise batın tomografisine ek olarak kontrol amaçlı çekildi. ÜBT ise 29( %65.90) hastada ameliyat sonrası kontrol amaçlı, 12 (%27.27) hastada ameliyat öncesi değerlendirme amaçlı, 3 (%6.81) hastada ise doğrudan batın travması olmadan, blastik travmanın etkilerini değerlendirmek için çekildi. ATT’de en sık gözlenen bulgu efüzyon (%47.7) idi. ÜBT’nin %61.36’sında patoloji gözlenmezken, %20.45’inde karaciğer lasersayonu gözlendi. ATT ve ÜBT’nin toplam maliyeti tüm toraks ve batın tomografisinin toplam maliyetinin yaklaşık yarısı kadardı. TARTIŞMA: Ateşli silah yaralanması sonrasında çekilen selektif alt toraks ve üst batın tomografileri sadece patolojiyi saptamada değil ameliyat sonrası takipte de etkili, hızlı, güvenilir, kost efektif bir görüntüleme yöntemi olarak kullanılabilir. Anahtar sözcükler: Alt toraks tomografisi; ateşli silah yaralanması; üst batın tomografisi. Ulus Travma Acil Cerrahi Derg 2020;26(4):613-619

doi: 10.14744/tjtes.2020.26862

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ORIGIN A L A R T IC L E

Effects of catheter orifice configuration (triple-hole versus end-hole) in continuous infraclavicular brachial plexus block on analgesia after upper limb surgery Mehmet Burak Eskin, M.D.,1

Ayşegül Ceylan, M.D.2

Department of Anesthesiology and Reanimation, University of Health Sciences, Gülhane Faculty of Medicine, Ankara -Turkey

Department of Anesthesiology and Reanimation, Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: The configuration of a nerve block catheter may affect the local anesthetic spread in epidural analgesia and continuous peripheral nerve blocks. This prospective and randomized study aims to compare the multi-orifice nerve block catheter with an end-hole catheter in ultrasound-guided continuous infraclavicular brachial plexus block (BPB) in terms of providing postoperative analgesia for the orthopedic upper limb surgery below the shoulder. The primary outcome measure was mean pain scores. Secondary outcome measures were the consumption of rescue analgesic and the amount of local anesthetics delivered by a Patient-Controlled Analgesia (PCA) device. METHODS: A total of 58 adult patients who underwent orthopedic upper limb surgery below the shoulder were randomly assigned into two groups: group end-hole catheter (EHC) (n=31) and group multi-orifice catheter (MOC) (n=27). All patients received a single-shot infraclavicular BPB using 100 mg lidocaine 2% and 75 mg bupivacaine 0.5% administrated through a Tuohy needle. Then, a multi–orifice (triple-hole) nerve catheter was placed in the group MOC and an end-hole (one-hole) catheter in the group EHC at the same location. Bupivacaine 0.125% was infused through the catheters via PCA (infusion rate: 2 mlh-1, automated regular bolus: 5 mlh-1, patient-controlled bolus: 3 ml, lock-out time: 1 hour, 4 hours limit: 40 ml). Pain intensity was evaluated using a visual analogue scale (VAS). RESULTS: Mean VAS scores were higher in group EHC than group MOC in the first postoperative day (p=0.001). Mean rescue analgesic consumption, the number of bolus demand on PCA, PCA bolus demand dose, and total PCA dose were higher in group EHC than group MOC during the first postoperative day (p<0.05). CONCLUSION: It is concluded that the use of MHC is more effective than EHC for continuous infraclavicular brachial plexus blocks in providing postoperative pain relief during the first 24 hours. Keywords: Brachial plexus block; catheter; infraclavicular; postoperative analgesia; ultrasound.

INTRODUCTION Peripheral nerve blocks (PNBs) are increasingly used as a sole anesthetic technique or as an adjunct to general anesthesia. [1] The introduction of the ultrasonography (US) allows realtime visualization of the target nerve, interfascial planes, as well as the needle, the catheter, and the spread of the local anesthetic (LA) during the procedure.[2] These advantages in-

crease the safety and quality of the postoperative analgesia. Thus, continuous PNBs became a crucial part of the multimodal analgesic regimen in recent years.[1,2] Like the dose of a LA, its spread around a nerve is important for a successful block. Several factors may affect LA spread, including the configuration of the catheter, the position of the catheter relative to the nerve, and the flow

Cite this article as: Eskin MB, Ceylan A. Effects of catheter orifice configuration (triple-hole versus end-hole) in continuous infraclavicular brachial plexus block on analgesia after upper limb surgery. Ulus Travma Acil Cerrahi Derg 2020;26:620-627. Address for correspondence: Mehmet Burak Eskin, M.D. Sağlık Bilimleri Üniversitesi, Gülhane Tıp Fakültesi, Anestezi ve Reanimasyon Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 304 59 18 / 5907 E-mail: mehmetburak.eskin@sbu.edu.tr Ulus Travma Acil Cerrahi Derg 2020;26(4):620-627 DOI: 10.14744/tjtes.2020.03302 Submitted: 09.04.2020 Accepted: 20.06.2020 Online: 25.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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rate of the LA through the catheter.[3] The catheter should be positioned, so its orifice(s) is/are close to the nerve and the catheter threading distance, that is, the catheter’s length past the tip of the cannula, should avoid displacement and coiling after insertion.[4] There are controversies about the catheter threading distance, but it was reported that a distance between 1–3 cm is optimal and >5 cm increased the risk of catheter coiling.[4] There are two types of PNB catheters in use: multi-orifice catheter (MOC) and end-hole catheter (EHC). MOCs are found to be superior to the EHCs in epidural analgesia due to a better spread of LA and providing alternative flow channels if one orifice obstruct.[5] However, only three studies exist in the literature that compares catheter configurations regarding postoperative analgesia in continuous PNBs.[4,6,7] In the first study, a MOC was compared with an EHC in continuous supraclavicular blocks and found superior to the EHC, but the catheter threading distances were different between study groups.[4] In the other two studies, no differences in postoperative analgesia were reported between catheters used for supraclavicular and femoral nerve blocks with similar catheter threading distances.[6,7] Epidural analgesia studies showed that the flow rate affects the LA spread from multi-orifice catheters. They function like end-hole catheters on a flow rate lower than 80 mlh-1. The flow was double or multi-orifice in a flow rate of 100–150 mlh-1 and multi-orifice if the flow rate is higher than 400 mlh-1. [8] Since high flow rates cannot be provided with a continuous infusion, automated regular boluses (ARB) with minimum 5ml (flow rate of approximately 100–150 mlh-1) was recommended.[9] US-guided continuous infraclavicular brachial plexus block (BPB) is generally preferred in our clinic for the upper extremity surgery below the shoulder due to a lower incidence of complications, including pneumothorax, phrenic nerve palsy, and Horner’s syndrome.[10] Both MOCs and EHCs are frequently used to provide perioperative anesthesia and analgesia. Similar to the interscalene groove, the posterior, median and lateral cords of the brachial plexus are located around the axillary artery in the infraclavicular region. This allows a sufficient spread of the LAs to the brachial plexus, which results in a rapid onset of the block with a high success rate in single- bolus injection and continuous infusion.[10] The present study aims to compare postoperative analgesia between multi-orifice and end-hole nerve catheters in the continuous infraclavicular brachial plexus blocks in patients undergoing orthopedic upper limb surgery below the shoulder. The primary outcome measure was postoperative pain scores. The secondary outcome measures were the comparison of rescue analgesic consumption, bolus and total doses of local anesthetics administered through the nerve catheter using patient-controlled analgesia (PCA). Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

MATERIALS AND METHODS Study Design This single-center, prospective and randomized study was conducted in the operating theatres of the University of Health Sciences Gülhane Training and Research Hospital between 17.10.2019 and 31.3.2020 after the hospital’s ethics committee approval (date: 12.10.2019, protocol no.19/938) and registered with the Clinical Trials.gov (NCT0420569). Written informed consent was obtained from patients. This study followed the Consolidated Standard of Reporting Trials (CONSORT) recommendations for reporting randomised controlled trials.

Inclusion Criteria American Society of Anesthesiologists physical status 1-2 patients aged between 18-80 years and scheduled for elective unilateral orthopedic upper limb surgery under the care of principal investigator below shoulder were included in this study. A research assistant invited all the patients for the participation, but definitive recruitment was by the principal investigator.

Exclusion Criteria The exclusion criteria included the patient’s refusal, pregnancy, and history of allergy to study drugs, neurological and cognitive disorders, coagulopathy, chronic pain disorder, and infection at the injection site.

Allocation and Randomization A sealed, opaque envelope containing allocated randomization was opened in the operating room before the block. Patients were allocated in a 1:1 ratio to one of two groups to receive a continuous infraclavicular BPB using a multi-orifice or an end-hole nerve catheter: Group Multi-orifice Catheter (group MOC, n=35) and group End-hole Catheter (Group EHC, n=35).

Infraclavicular Brachial Plexus Block Procedure And Catheter Insertion After arriving into the operating room, the patients were monitorized with electrocardiogram, pulse oximetry, and non-invasive blood pressure. Midazolam (2–3 mg) and fentanyl (0.05 mg) were administered for sedation and analgesia after establishing an intravenous (IV) access. A single staff anesthesiologist who was experienced in peripheral nerve blocks under the US guidance performed all blocks. The patient was placed supine with the head turned to the contralateral shoulder. The arm was abducted to 90 degrees. Thus, pectoral muscles, brachial plexus chords, and axillary artery could be better visualized. The coracoid process was identified by palpating the bony prominence medial to the shoulder. A linear US probe (ultrasound machine (SonoSite X-Porte, SonoSite, Bothell, WA, USA) was placed in a parasagittal 621

Eskin et al. Effects of catheter orifice configuration in continuous infraclavicular BPB on analgesia after upper limb surgery

plane medial to the coracoid process and inferior to the clavicle. By preliminary scanning from medial to lateral, posterior, lateral and medial cords of the brachial plexus were visualized around the axillary artery. A non-stimulating 17-gauge (G) Tuohy needle with a 19 G non–stimulating open-tip, triple hole EHC (Contiplex FX set, CNBFX350C, B.Braun Medical Inc., USA) or with a 19 G non–stimulating closed tip MHC (Contiplex FX set, CNBFX350O, B. Braun Medical Inc., USA) were used in the group EHC and the group MOC, respectively. The triple-hole orifices are located approximately 6, 9 and 12 mm from the MOC tip and radially orientated at 4, 8 and 12 o’clock. All catheters were cut at the proximal end to a length of 25 cm to minimize the flow pressure gradient between each catheter’s proximal end and orifice(s).[6] After sterile preparation and dressing, the US probe was placed in a sterile cover. The Tuohy needle was inserted using an in-plane approach from the cephalic end of the probe with an insertion point inferior to the clavicle after skin infiltration with 2 ml of 2% prilocaine. The needle was passed through pectoral muscles and advanced to the axillary artery. It was placed at the six o’clock position relative to the axillary artery. The location was confirmed by injecting 2 ml of 2% lidocaine after careful aspiration. Eighteen ml of a LA mixture containing 6 ml lidocaine 2% (120 mg) and 14 ml bupivacaine 0.05% (70 mg) was administered to achieve a Ushaped spread of LA around the axillar artery (expected flow rate: 360–550 mlh-1). The catheter was advanced through the needle and placed 4–5 cm beyond the needle tip. The Tuohy needle was removed. Then, the catheter was withdrawn under the US guidance as the catheter threading distance was kept between 1–1.5 cm. The correct position of the catheter was controlled with the US, and the remaining LA (2 ml) was further administered to check its free flow through the catheter. The catheter was tunneled towards the sternoclavicular region to reduce the risk of removal. A second anesthesiologist who was blinded to the study groups recorded study parameters and managed the patients. The surgical procedure was started after complete sensory and motor block was achieved, which were assessed every five minutes for 30 minutes. The sensory block was assessed with the pinprick sensation at five nerve distributions, including median, radial, ulnar, musculocutaneous, and medial cutaneous nerves of the forearm. The motor block was assessed using the Bromage scale in the hand and arm. Midazolam (1–2 mg) was administered if requested by the patient. If a complete sensory blockade was not achieved, the case was termed as a block failure. In that case, a rescue block for the unblocked nerve (such as an ulnar block at the elbow) or a supplemental LA infiltration was tried. If those interventions failed, general anesthesia was administered.

Follow–up Period All patients were followed in the post anesthesia care unit until they met the discharge criteria and then they were dis622

charged to the service. The operative arm was kept in a sling during the postoperative period. The patients were received a multimodal analgesic regimen at the postoperative period: paracetamol 1000 mg IV with eight hours intervals, dexketoprofen 50 mg IV with 24 hours intervals, continuous peripheral nerve block-PCA (0.125% bupivacaine; basal rate: 2 mlh-1; automated regular boluse: 5mlh-1; bolus dose on demand: 3 ml, lockout time: 60 min; 4-hours limit: 40 ml). Postoperative pain was evaluated using a Visual Analogue Scale (VAS; 0–10 cm) before the block, with four hours intervals during the first 24 hours, then with 12 hours intervals until the postoperative 72. hours and recorded. Pethidine 0.5 mgkg-1 was IV given as a rescue analgesic if the VAS score was >3. Patients with normal vital parameters were discharged from the hospital on the third postoperative day after removal of the catheter when the VAS score was <3. The patient’s satisfaction level was assessed by VAS ranging from not satisfied (score-0) to fully satisfied (score-10) with the treatment outcomes at discharge. The following criteria were recorded and compared between groups: Demographic data, mean operative times (minutes), VAS scores, time to first rescue analgesic (hour) and rescue analgesic consumption (mg), number of bolus demand via PCA, bolus dose on demand (ml), and total LA consumption (ml) via PCA, patient’s satisfaction score, and complications. Complications were defined as complications related to PNB and surgery (nerve damage, LA toxicity, bleeding, infection, catheter removal, and thromboembolism) and to systemic analgesics (respiratory distress, nausea, vomiting, itching, constipation, drowsiness, dizziness, and dry mouth).

Statistical Analysis Statistical analysis was performed using IBM SPSS Statistics version 21 (IBM SPSS Inc., Chicago, IL). The sample size was calculated to detect a minimum clinically important difference of 20% in the VAS scores between two groups. A power analysis indicated that minimum of 50 cases would be needed to achieve 80% power with an alpha error of 0.05, equivalent to an effect size of 0.8. We aimed to enroll a minimum of 70 cases (35 in each arm) to allow 15% through withdrawals or loss to follow up. Descriptive statistics were used as mean, standard deviation, and median for continuous data and frequency and percentage for categorical data. The normal distribution of continuous data was analyzed using the Kolmogorov-Smirnov test. Mean of variables between groups were compared with Student’s t-test when data are with normal distribution, and with Mann-Whitney U test when data were without normal distribution. Pearson Chi-square test was used to assess a difference in the distribution of categorical variables between groups. P<0.05 was considered as statistically significant.

RESULTS Of total of 70 patients, 12 patients were excluded from this Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Eskin et al. Effects of catheter orifice configuration in continuous infraclavicular BPB on analgesia after upper limb surgery

Assed for eligibility (n=70) Excluded (n=0) • Not meeting inclusion criteria

Enrollment

• Declined to participate (n=0)

Randomized (n=70)

Allocation Allocated to intervention (n=35)

Allocated to intervention (n=35)

• Received allocated intervention

Group End-hole catheter

Group Multi-orifice catheter

Lost to follow-up (n=4)

Lost to follow-up (n=8)

• Block failure (n=2)

• Block failure (n=3)

Follow-up

• Catheter removal (n=1)

• Early discharge (n=1)

• Early discharge (n=4)

Analyzed (n=31)

Analyzed (n=27)

• Excluded from analysis (n=0)

Analysis

Figure 1. Study flow diagram.

study. The block was failed in five patients (2 in group EHC, three patients in group MOC). These patients were received Table 1. Comparison of the demographic data between study groups

Group EHC Group MOC (n=31) (n=27)

general anesthesia. The catheter was removed in one patient in both groups in the first postoperative 24 hours, and those patients were received an IV tramadol PCA. Five patients (1 in Table 2. Comparison of the Visual Analogue Scale scores between study groups

Group EHC Group MOC (n=31) (n=27)

Gender, n (%)

Female

11 (35.5)

11 (40.7)

Male

20 (64.5)

16 (59.3)

33.7±10.3

36.0±9.5

0.681

VAS Scores (hrs.) Preoperative

5.2±1.7

5.3±1.3 0.150

0.398

0.5±0.3

0.4±0.2

0.523

1.9±0.5

1.7±0.1 0.150

ASA status, n (%)

4.0± 0.8

3.6±0.9

0.150

16 (51.6)

14 (51.9)

0.896

12.

4.6±0.8

2.7±1.1

0.001

15 (48.4)

13 (48.1)

Age (years) Body mass index (kgm ) -2

25.4±5.8

25.1±3.3

Surgery (ORIF), n (%)

Distal humerus /elbow

9 (29.0)

8 (29.63)

0.316

16.

2.9±0.7

2.3±0.7 0.030

1.4± 0.9

1.7±0.9

20.

0.075

0.443

24.

0.6±0.9

0.2±0.5

0.136

48.

0.1±0.3

0.0±0.0

0.138

72.

0.0±0.0

0.138

1.9±1.9

1.5±1.5 0.008

Forearm

12 (38.7)

11 (40.74)

0.616

Hand/wrist bones

10 (32.3)

8 (29.63)

0.205

EHC: End-hole catheter; MOC: Multi-orifice catheter; ASA: American Society of Anesthesiologists; ORIF: Open reduction and internal fixation. Values are presented as mean ± standard deviation, numbers and/or proportion (n, %). P<0.05 was considered as statistically significant.

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Total

EHC: End-hole catheter; MOC: Multi-orifice catheter; VAS: Visual Analogue Scale. Values are presented as mean ± standard deviation. P<0.05 was considered as statistically significant.

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group EHC and 4 in group MOC) refused to participate in this study in the follow-up period. Of the remaining 58 patients, the EHC group included 31 patients and the MOC group included 27 patients (Fig. 1). Demographic characteristics, surgery, and mean operating times were similar between groups (p>0.05) (Table 1). It was observed that mean VAS scores of the groups reduced to a clinically insignificant level (<1) at the 48. hours and a rescue analgesic was not required after 24. hours. Thus, continuous PNB was stopped and catheters were removed after 48. hours. Oral paracetamol (500 mg) was administered as necessary. A total of 10 VAS measurements (preoperative, at postoperative 4., 8., 12., 16., 20., 24., 48., and 72. hours) and three postoperative pain therapy assessments (0.–12., 12.–24., and 24.–48. hours) were selected out for each case which were recorded at similar times.

Group EHC Group MOC

VAS Score

Primary Outcome Measure: Mean preoperative VAS scores were 5.2±1.7 in group EHC and 5.3±1.3 in group MHC (p=0.150) (Table 2). Postoperative mean VAS scores were similar and lower than 3 at postoperative 0. and 4. hours but were increased to >3 at 8. hours in both groups (p>0.05). Mean VAS scores were decreased in group MOC at 12. hours but increased to the highest level in group EHC (2.7±1.1 vs. 4.6±2.7; p=0.001). VAS scores gradually decreased in both groups from postoperative 16. hours to the end of the study period, but the difference between groups was significant at 16. hours in favor of the EHC group (2.9±1.1 vs. 2.3±0.7; p=0.030). VAS scores were found to be reduced to a clinically insignificant level (<1) at 48. hours (Fig. 2).

0 8

Time (hours)

Figure 2. VAS score in groups between postoperative 8.–72. hours. EHC: End-hole catheter; MOC: Multi-orifice catheter; VAS: Visual Analogue Scale.

Secondary Outcome Measures: Time to first rescue analgesic was lower, and mean consumption of the rescue analgesic was higher in the group EHC compared to the group MOC (p<0.05; Table 3). Number of PCA bolus demands, bolus PCA doses, and total PCA doses were higher in

Table 3. Comparing postoperative analgesia between study groups Time to first rescue analgesic (h)

Group end-hole catheter (n=31)

Group multi-orifice catheter (n=27)

7.13±1.2

7.50±0.7

0.030

Rescue analgesic consumption (mg)

0.–12. hrs.

16.1±23.8

3.7±13.3

0.017

12.–24. hrs

35.5±26.4

18.5±24.6

0.021

24.–48. hrs.

0±0

Patient controlled analgesia bolus on demand (n)

0.–12. hrs.

6.6±2.4

2.4±2.2

0.001

12.–24. hrs

7.1±1.5

1.8±1.1

0.002

24.–48. hrs.

1.5±1.5

1.4±0.8

0.358

Bolus patient controlled analgesia dose on demand (ml)

0.–12. hrs.

19.0±6.3

6.9±4.1

0.001

12.–24. hrs

20.9±3.1

5.4±2.3

0.002

24.–48. hrs.

4.2±1.5

4.1±1.0

0.241

Total patient controlled analgesia dose (ml)

0.–12. hrs.

100.1±4.5

89.9±4.0

0.001

12.–24. hrs

102.8±4.4

89.2±5.1

0.002

24.–48. hrs.

171.2±2.4

170.2±1.9

0.560

Values are presented as mean ± standard deviation. P<0.05 was considered as statistically significant.

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Eskin et al. Effects of catheter orifice configuration in continuous infraclavicular BPB on analgesia after upper limb surgery

group EHC than the group MOC between postoperative 0.– 12. hours and 12.–24. hours (p<0.05) (Table 3). There were no signs and symptoms related to local anesthetic toxicity observed and similar minor complications were treated in groups (p>0.05) Mean patient satisfaction scores were higher in the group MOC than in the group EHC (p=0.013).

DISCUSSION To our knowledge, this is the first prospective and randomized study in the literature which compares nerve catheters with different tip configuration concerning postoperative analgesia in continuous infraclavicular BPBs. In this study, all procedures were performed in a standard fashion. The Tuohy needle was positioned at a six o’clock position under the axillary artery with similar catheter threading distances of 10–15 mm. It should be noted that the multi-modal analgesic regimen in this study reduced postoperative pain scores in both groups to a minimum level, where rescue analgesics were not required after 24. hours. Mean VAS scores increased to >3 at postoperative 8. hours in both groups that were attributable to the resolution of sensory block. The differences in VAS scores were significant at 12. and 16. hours in favor of the MOC group between groups. The results showed that a continuous infraclavicular BPB using multi-orifice nerve catheter provided superior pain relief than the end-hole catheter in the postoperative first 24 hours. This was supported by the fact that rescue analgesic consumption, number and dose of bolus demand were about 2–3 folds higher in the group EHC than group MOC in the first 24 hours, which decreased the VAS scores in the group EHC to a similar level as in the group MHC. The possible explanation might be due to the better spread of LA through the MOC than the EHC. Automated regular boluses of 5 ml.h-1 (flow rate 100–150 ml.h-1) might provide sufficient LA spread from all orifices of the MOC, so LA was distributed more efficiently to the cords around the artery compared to the EHC. The result of this current study is consistent with previous studies which have reported that multi-orifice epidural catheters improved analgesia and reduced local anesthetic consumption compared to end-hole catheters.[5,11,12]

ministered using the catheter after the induction of the general anesthesia and before the surgery. After the surgery, another 15 ml of lignocaine 1.5% were administered through the catheter in the postanesthesia care unit if the patients reported a numerical rating pain score of more than two. If pain persisted 30 minutes after this bolus, the catheter was replaced with the same catheter type and a further 15 ml of ropivacaine 0.375% was administered. However, the exact position of the catheter relative to the roots was not confirmed under the vision of the US although the catheters were blindly advanced through the catheter and then withdrawn until 3 cm. Also, there was a difference in the difficulty with catheter threading between groups. The catheter was threaded more difficult in the end-hole group compared to the multi-hole groups, which might be contributed to the observed difference in the catheter performance as outlined by the author. Additionally, the flow rate might be effective for a successful spread of LA through catheters, but the dose of the LA using 15 ml might not be an effective dose to achieve a difference in analgesia between catheters in the interscalene block irrespective of the configuration of the catheter which was supported with another two boluses (total 30 ml) after the surgery. In the second study, 20 ml of 1% lidocaine was administered through a six-hole or an end –hole catheter which was placed between the femoral nerve and the iliopsoas muscle under the US guidance in combination with a single- shot sciatic nerve block before the general anesthesia in patients undergoing total knee arthroplasty.[7] Total local anesthetic consumption, mean pain scores, opiate requirements, patient satisfaction, and technical problems did not differ between groups. The authors of this study stated that this similarity might be due to the trapping of the catheter between the nerve and the muscle and LA is pushed around the nerve irrespective of the number of holes. However, it was not clear

The results of this study were in contrast to the previous two studies, which have reported no difference between the end hole and multiple hole nerve catheters concerning postoperative analgesia in continuous peripheral nerve blocks.[6,7] In the study conducted by Frederickson, an end-hole catheter was compared with a triple-hole and six- hole catheter, which were positioned 3 cm beyond the needle tip lateral to the C5/C6 roots for a continuous interscalene analgesia.[6] The catheters were advanced blindly 5 to 7 cm beyond the needle tip, then, the needle was removed and the catheter was withdrawn until 3 cm remained past the original needle tip position. In addition, 15 ml of ropivacaine 0.375% was adUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Figure 3. Ultrasound image of infraclavicular catheterization. PMaM: Pectoralis major muscle; PMiM: Pectoralis minor muscle; LC: Lateral cord; MC: Medial cord; PC: Posterior cord; Red arrow: Peripheral nerve catheter; White arrowheads: Needle.

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Eskin et al. Effects of catheter orifice configuration in continuous infraclavicular BPB on analgesia after upper limb surgery

whether the pain after the knee arthroplasty arose from the sensory distribution of the sciatic nerve or the femoral nerve.

A.C.; Materials: M.B.E., A.C.; Data: M.B.E., A.C.; Analysis: M.B.E., A.C.; Literature search: M.B.E., A.C.; Writing: M.B.E., A.C.; Critical revision: M.B.E., A.C.

There were also several differences between the current and previous studies. First difference is the administration of the bolus LA doses for surgical anesthesia. LA was administrated through the nerve catheter in previous studies.[4,6,7] However, in our study, LA was administrated through the Tuohy needle, and then a nerve catheter was placed (Fig. 3). We preferred this method because the hydrodissection of the surrounding tissue with LA could facilitate the placement of the catheter in the exact position.[13] Also, the high flow rate provided by the bolus administration could gain an advantage to group MHC concerning LA spread from the very beginning of this study, but this study aimed to compare postoperative analgesia. The second difference was the target of LA injection. Since the target was the axillary artery in the infraclavicular blocks, identification of the plexus cords was not necessary as in the supraclavicular block.[13]

Conflict of Interest: None declared.

Local anesthetic toxicity is a potential problem due to the accumulation of the continuous peripheral nerve blocks. The reported toxic concentration of bupivacaine is 2 µg.ml-1. [14] In a study, mean plasma bupivacaine level was measured 1.78±0.59 µg.ml-1 with a bolus dose of 2.5 mg.kg-1 bupivacaine followed by a continuous infusion of 0.125% plain bupivacaine at 12 ml.h-1 during 48 hours without signs of LA toxicity.[15] In our study, 0.125% bupivacaine was administrated at continuous infusion (2 ml.h-1), and 5 ml automated boluses per hour. 3 ml boluses were used on demand with one-hour lockout interval. Although the plasma bupivacaine levels were not measured, the maximum infusion rates were not higher than 10 ml.h-1 (3.5–8.5 ml.h-1) throughout the study period.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Ilfeld BM. Continuous Peripheral Nerve Blocks: An Update of the Published Evidence and Comparison With Novel, Alternative Analgesic Modalities. Anesth Analg 2017;124:308−35. 2. Joshi G, Gandhi K, Shah N, Gadsden J, Corman SL. Peripheral nerve blocks in the management of postoperative pain: challenges and opportunities. J Clin Anesth 2016;35:524−9. 3. Plante T, Rontes O, Bloc S, Delbos A. Spread of local anesthetic during an ultrasound-guided interscalene block: does the injection site influence diffusion?. Acta Anaesthesiol Scand 2011;55:664−9. 4. Fredrickson MJ, Ball CM, Dalgleish AJ. Catheter orifice configuration influences the effectiveness of continuous peripheral nerve blockade. Reg Anesth Pain Med 2011;36:470−5. 5. Segal S, Eappen S, Datta S. Superiority of multi-orifice over single-orifice epidural catheters for labor analgesia and cesarean delivery. J Clin Anesth 1997;9:109−12. 6. Fredrickson MJ. Randomised comparison of an end-hole, triple-hole and novel six-hole catheter for continuous interscalene analgesia. Anaesth Intensive Care 2014;42:37−42. 7. Novello-Siegenthaler A, Hamdani M, Iselin-Chaves I, Fournier R. Ultrasound-guided continuous femoral nerve block: a randomized trial on the influence of femoral nerve catheter orifice configuration (six-hole versus end-hole) on post-operative analgesia after total knee arthroplasty. BMC Anesthesiol 2018;18:191. 8. Fegley AJ, Lerman J, Wissler R. Epidural multiorifice catheters function as single-orifice catheters: an in vitro study. Anesth Analg 2008;107:1079−81.

This study has several limitations. Since this study was designed to evaluate postoperative pain relief, the resolution of the sensory and motor blocks was not systematically evaluated. The second limitation was relatively limited numbers of patients that were included in this study. The last limitation was that the measurements for postoperative analgesia that were collected while patients were at rest.

9. Fredrickson MJ, Abeysekera A, Price DJ, Wong AC. Patient-initiated mandatory boluses for ambulatory continuous interscalene analgesia: an effective strategy for optimizing analgesia and minimizing side-effects. Br J Anaesth 2011;106:239−45.

Conclusion

11. D’Angelo R, Foss ML, Livesay CH. A comparison of multiport and uniport epidural catheters in laboring patients. Anesth Analg 1997;84:1276−9.

In conclusion, the use of the multi-orifice catheters in continuous infraclavicular BPB provided better postoperative analgesia than the end-hole catheter for the orthopedic upper limb surgery below the shoulder concerning lower VAS scores, reduced consumption of rescue analgesic and local anesthetics, and higher patient’s satisfaction scores. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.B.E., A.C.; Design: M.B.E., A.C.; Supervision: M.B.E., A.C.; Fundings: M.B.E., 626

10. Mariano ER, Sandhu NS, Loland VJ, Bishop ML, Madison SJ, Abrams RA, et al. A randomized comparison of infraclavicular and supraclavicular continuous peripheral nerve blocks for postoperative analgesia. Reg Anesth Pain Med 2011;36:26−31.

12. Dickson MA, Moores C, McClure JH. Comparison of single, end-holed and multi-orifice extradural catheters when used for continuous infusion of local anaesthetic during labour. Br J Anaesth 1997;79:297−300. 13. NysoRA. Introduction to Ultrasound-Guided Regional Anesthesia. Available from: https://www.nysora.com/foundations-of-regional-anesthesia/equipment/introduction-ultrasound-guided-regional-anesthesia/. Accessed April 14, 2020. 14. Christie LE, Picard J, Weinberg GL. Local anaesthetic systemic toxicity. BJA Education 2015;15:136–42. 15. Estève M, Veillette Y, Ecoffey C, Orhant EE. Continuous block of the femoral nerve after surgery of the knee: pharmacokinetics of bupivacaine. [Article in french]. Ann Fr Anesth Reanim 1990;9:322−5.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Sürekli infraklaviküler brakial pleksus bloğunda kateter ucu konfigürasyonunun (üç delikliye karşı uçtan delikli) üst ekstremite cerrahisi sonrası analjeziye etkisi Dr. Mehmet Burak Eskin,1 Dr. Ayşegül Ceylan2 1 2

Sağlık Bilimleri Üniversitesi, Gülhane Tıp Fakültesi, Anestezi ve Reanimasyon Anabilim Dalı, Ankara Gülhane Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, Ankara

AMAÇ: Sinir bloğu kateterinin konfigürasyonu epidural analjezi ve sürekli periferik sinir bloklarında lokal anestezik yayılımını etkileyebilmektedir. Bu ileriye yönelik ve randomize çalışmanın amacı, omuz seviyesinin altında gerçekleştirilen üst ekstremite cerrahilerinde, ultrason rehberliğinde yapılan sürekli infraklaviküler brakiyal pleksus bloğunda (BPB) üç delikli sinir bloğu kateteri ile tek delikli kateterin ameliyat sonrası analjezik etkinliklerini karşılaştırmaktır. Primer sonuç ölçümleri ortalama ağrı skorlarıydı. Sekonder sonuç ölçümleri, kurtarıcı analjezik tüketimi ve hasta kontrollü analjezi (PCA) cihazı tarafından gönderilen lokal anestezik miktarlarıydı. GEREÇ VE YÖNTEM: Omuz seviyesinin altında üst ekstremite cerrahisi uygulanan toplam 58 erişkin hasta rastgele iki gruba ayrıldı: Tek delikli kateter (EHC) grubu (n=31) ve çok delikli kateter (MOC) grubu (n=27). Tüm hastalara, Tuohy iğnesi ile 100 mg %2 lidokain and 75 mg %0.5 bupivakain ile tek doz infraklaviküler BPB uygulandı. Daha sonra MOC grubuna çok delikli (üç delikli) bir sinir kateteri ve EHC grubuna aynı seviyeden uçtan delikli (tek delikli) kateter yerleştirildi. PCA yoluyla %0.125 bupivakain, kateterlerden infüzyon edildi (infüzyon hızı: 2 ml/sa, otomatik düzenli bolus: 5 ml/sa, hasta kontrollü bolus: 3 ml, kilitleme süresi: 1 saat, 4 saatlik limit: 40 ml). Ağrı şiddeti görsel analog skala (VAS) kullanılarak değerlendirildi. BULGULAR: VAS skorları ameliyat sonrası ilk gün grup EHC’de, grup MOC’den daha yüksekti (p=0.001). Ortalama kurtarma analjezik tüketimi, PCA üzerindeki bolus sayısı, PCA bolus dozu ve toplam PCA dozu, grup EHC’de ameliyat sonrası ilk gün grup MOC’dan daha yüksekti (p<0.05). TARTIŞMA: Infraklavikular sürekli sinir bloğunda MHC kullanımının, ilk 24 saat ameliyat sonrası ağrıyı azaltmada EHC’den daha etkili olduğu sonucuna vardık. Anahtar sözcükler: Ameliyat sonrası analjezi; brakiyal pleksus bloğu; infraklavikular; kateter; ultrason. Ulus Travma Acil Cerrahi Derg 2020;26(4):620-627

doi: 10.14744/tjtes.2020.03302

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CA S E R EP O RT

Acute spinal epidural hematoma: A case report and review of the literature Ezgi Akar, M.D.,1 Ahmet Öğrenci, M.D.,2 Orkun Koban, M.D.,2 Mesut Yılmaz, M.D.,3 Sedat Dalbayrak, M.D.2 1

Department of Neurosurgery, University of Health Sciences, Haydarpaşa Numune Training and Research Hospital, İstanbul-Turkey

Department of Neurosurgery, Okan University Faculty of Medicine, İstanbul-Turkey

Department of Neurosurgery, Neurospi̇ nal Academy, İstanbul-Turkey

ABSTRACT Spinal epidural hematoma (SEH) is a rare but a significant cause of spinal cord compression and neurologic deficits. Its etiology is usually unknown and requires emergency intervention.The present study aims to review the clinical significance, treatment strategies and clinical outcomes of traumatic SEH with a rare case presentation. Our patient was a 42-year-old female who presented with back pain and loss of sensation and strength in the legs. The patient did not have any disease and did not use anticoagulant drugs. The patient developed numbness in her legs half an hour after having a traditional back walking massage due to occasional back pain. She was paraplegic and anesthetic when seen in our clinic.Thoracic computed tomography (CT) and magnetic resonance imaging (MRI) revealed posterior epidural hemorrhage at Th3-Th4 levels. In the 12th hour, the hematoma was evacuated by an emergency decompressive hemilaminectomy. At the postoperative 24th hour, the patient had symptomatic improvement, and in the sixth month, the patient was mobilized with support. SEH is a rare condition that should be considered in patients with sudden onset of back pain and extremity weakness. Although the gold standard diagnostic tool is MRI, CT is often sufficient to avoid delayed surgery. Immediate surgical decompression (laminectomy/hemilaminectomy) should be performed in cases diagnosed with SEH with neurological deficits. Keywords: Decompressive surgery; hemilaminectomy; magnetic resonance imaging; spinal epidural hematoma.

INTRODUCTION Spinal epidural hematoma (SEH) is a very rare but a serious cause of acute neurological deterioration requiring early diagnosis and rapid surgical treatment. SEH has two different types as traumatic and spontaneous.[1] According to the literature data, traumatic SEH occurs in 0.5 to 1.7% of all spine traumas, but the incidence increases up to 9% in patients with rheumatologic disease.[2] Approximately 20–30% of all SEHs occur due to post-traumatic reasons.[3] Traumatic SEH may appear with traumatic spine injuries, as a complication of postoperative surgical procedures (e.g., instrumentation procedures, vertebro and kyphoplasty) and after spinal injection procedures.

Traumatic SEH may sometimes occur even with a simple lumbar puncture procedure (0.1%–0.24%).[4] According to the literature data, there are several cases with SEH with minor trauma that arise from spine manipulation therapy.[4] [3]

In the present study, we discussed a case who was admitted to our emergency department with SEH with progressive neurological deficits after having back walking massage, which is an ancient Eastern massage method (Fig. 1). We discussed our case who underwent surgical treatment due to thoracal SEH in the light of the current literature. To our knowledge, there is no reported case with SEH after back walking massage in the literature.

Cite this article as: Akar E, Öğrenci A, Koban O, Yılmaz M, Dalbayrak S. Acute spinal epidural hematoma: A case report and review of the literature. Ulus Travma Acil Cerrahi Derg 2020;26:628-631. Address for correspondence: Ezgi Akar, M.D. Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul, Turkey Tel: +90 216 - 386 82 63 E-mail: ezgiaycicek@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):628-631 DOI: 10.14744/tjtes.2019.60956 Submitted: 30.09.2019 Accepted: 15.12.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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massage due to long-lasting and occasionally seen low back pain. Half an hour after the back walking massage, she experienced severe back pain and numbness and weakness in her legs. Laboratory analyses, including platelet count, bleeding time (60–240 seconds), clotting time (300–900 seconds), were within normal limits. Imaging studies (CT and MRI) revealed a lesion in the posterior epidural space consistent with acute hemorrhage at the levels of Th3 and Th4 vertebrae (Fig. 2a–c). At the 12th hour, decompressive hemilaminectomy was performed to Th3-Th4 levels and the hematoma was evacuated. Control MRI was performed within 24 hours postoperatively (Fig. 3a, b). Passive exercises were started on the postoperative second day, and she was referred to the physical therapy program in the second week. In the sixth postoperative month, her leg strength was complete on the left side and 3/5 on the right side, and she was mobilized with support.

Figure 1. Back walking massage.

CASE REPORT

DISCUSSION

A 42-year-old female patient was admitted to the emergency department due to back pain, and acute onset of sensory changes and weakness in the lower extremity. The patient was referred to us from another center. When the patient was evaluated in the emergency department, about 10 hours had passed since the beginning of the incident. The patient was conscious and without respiratory distress and with normal vital signs. Physical examination revealed anesthesia below Th3 level and paraplegia, and lack of anal sensation and tonus. She had no history of hypertension, severe trauma, anticoagulant drug use and bleeding dyscrasia. The patient stated that someone had walked on her back to

(a)

(b)

(c)

Figure 2. (a-c) Preoperative CT and MRI images.

(a)

(b)

Figure 3. (a, b) Postoperative axial and sagittal MRI images.

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SEH is a rare disease occurring due to bleeding in the epidural region, divided into two main groups, spontaneous and traumatic based on its etiopathogenesis.[1] SHE was first defined by Jackson[5] in 1869 with the autopsy of a young woman who died due to respiratory distress, following a regular loss of strength in the arms and legs. While the pathogenesis of the hematoma has not been fully understood, the majority of the authors believe that the internal posterior epidural venous plexus is the anatomic structure responsible for the hematoma.[6] Causes which rapidly increase the intra-abdominal and thoracic pressure, such as pregnancy, coughing, sneezing, vomiting and urinating, may cause venous epidural plexus lesion.[7] We should note that 40–60% of the phenomenon is idiopathic-spontaneous; the use of anticoagulant and antiagregant medication is the most frequent underlying causes.[4] Furthermore, SEH development has been reported in cases that cause a tendency to genetic and metabolic coagulopathy, such as vascular malformations, spinal puncture, and use of drugs.[3] Traumatic SEH is frequently observed in adults and males (≥40 years old) and cervical (mostly C6 segment) and upper t-spine. It is mostly related to high-energy traumas and vertebral fractures, and SEH is more likely in patients with rheumatic diseases.[7,8] Some theories have been asserted about the cause of epidural venous hematoma; the main theory is that bone fragment broken in traumatic phenomena directly tears and stretches the epidural veins and cause hemorrhage around the spinal cord.[3,5] However, in high-energy traumatic spinal injuries, no epidural hemorrhage is observed and unlike the assumptions, there is a minor trauma in the majority of the SEH cases.[3] When it comes to minor trauma, it may arise from significant dynamic stress, such as stretching exercises, injuries during physical activities, sports, daily routine activities and chiropractic spinal manipulation therapy.[3,9,10] Even though there are rare phenomena reported with the spinal manipulation therapies, there are not any SEH 629

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phenomena in the literature related to back walking massage which is an ancient Eastern massage method. Back walking massage is a massage technique that has a historical value in especially Eastern and Far Eastern societies due to nonspecific back pains (Fig. 1). The loss of strength and sensation half an hour later than the massage, the lack of damage in bone and ligamentous structures in radiological examinations make us think that damage and hemorrhage has occurred in posterior epidural venous plexus with a minor trauma that arises from back walking massage. The gold standard technique in diagnostics is MRI; however, it is determinative of the treatment in case of emergency in CT. Hemorrhage in CT is considered as a hyperdense epidural mass. Advantages of CT are that it is easily accessible, cheap, suitable for claustrophobic patients and can be used in patients with a metallic implant. In several cases, surgery with CT can be sufficient to accelerate the treatment. When it comes to MRI, it clearly shows the hematoma pressing on the epidural, vulnerability rate of the cord, lateralization of the hematoma. It is characteristic of SEH that the fusiformlooking lesion in the epidural interval gives a mosaic pattern in irregular intensity depending on methemoglobin degradation.[11] The appearance of clinical findings and the factors determining the severity of the symptom is the amount of hemorrhage, its localization and cord compression time. Because spinal cord is under mechanic pressure, this causes deterioration of microcirculation, central necrosis, edema in axone and myelin sheath and finally causing neurodeficits.[12] Increasing duration of pressure on the spinal cord causes disseminated tissue injury, increase in severity and permanence of deficit.[12] Therefore, surgery is recommended as soon as possible. Early treatment of cord compression can decrease mechanic, histologic and biochemical injuries. Thus, time passing between the surgical intervention with the appearance of symptoms is one of the most important factors.[13] Another important factor that is definitive in the postoperative neurological final condition is a pre-operative neurological examination of the patient.[12,13] The worse is the condition during motor and sensation examination before surgery less is the expectation for post-operative amelioration. Our patient has been on surgery after about 12 hours due to delay that arises from transfer from the epicenter. When the patient came, she was paraplegic and anesthetic. Postoperative, the patient was only able to be mobilized with support in the sixth month. In patients who have no deficit and only pain, spontaneous hematoma resorption and amelioration have been reported with analgesic treatment and rest. However, SEH cases appear with frequently progressive neurological deficits.[10,11] In this case, along with decompression, a hematoma is required to be excreted with urgent surgical intervention. Reaching out to the hemorrhage with total or partial laminectomy decompression can be applied in the cord.[13] Decompression level is determined based on the amount of hemorrhage; however, 630

there is instability risk in long-term levels of laminectomies. Total laminectomy is applied to the areas where hemorrhage is most intense, and hemilaminectomy can be performed in other sections.[13,14] As a result, SEH should be kept in mind in patients with acute symptoms of increased spinal cord pressure. In cases when an MRI may delay the treatment, CT can provide sufficient findings in most of the cases. Even minor trauma may cause SEH. The most determinative characteristic of our case is that a traditional massage method may cause SEH with paraplegia. The literature review has not shown any similar case. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.Ö., S.D.; Design: A.Ö., E.A.; Supervision: S.D., M.Y.; Materials: A.Ö., O.K.; Data: A.Ö., E.A.; Analysis: A.Ö., E.A.; Literature search: M.Y., O.K.; Writing: E.A.; Critical revision: E.A., A.Ö., O.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Mukerji N, Todd N. Spinal epidural haematoma; factors influencing outcome. Br J Neurosurg 2013;27:712–7. 2. Caron T, Bransford R, Nguyen Q, Agel J, Chapman J, Bellabarba C. Spine fractures in patients with ankylosing spinal disorders. Spine (Phila Pa 1976) 2010;35:E458–64. 3. Domenicucci M, Mancarella C, Santoro G, Dugoni DE, Ramieri A, Arezzo MF, et al. Spinal epidural hematomas: personal experience and literature review of more than 1000 cases. J Neurosurg Spine 2017;27:198−208. 4. Lidder S, Lang KJ, Masterson S, Blagg S. Acute spinal epidural haematoma causing cord compression after chiropractic neck manipulation: an under-recognised serious hazard?. J R Army Med Corps 2010;156:255–7. 5. Jackson R. Case of spinal apoplexy. Lancet 1869;2:5–6. 6. Groen RJ. Non-operative treatment of spontaneous spinal epidural hematomas: a review of the literature and a comparison with operative cases. Acta Neurochir (Wien) 2004;146:103–10. 7. Hsieh CT, Chiang YH, Tang CT, Sun JM, Ju DT. Delayed traumatic thoracic spinal epidural hematoma: a case report and literature review. Am J Emerg Med 2007;25:69–71. 8. Anipindi S, Ibrahim N. Epidural Haematoma Causing Paraplegia in a Patient with Ankylosing Spondylitis: A Case Report. Anesth Pain Med 2017;7:e43873. 9. Lee TH, Chen CF, Lee TC, Lee HL, Lu CH. Acute thoracic epidural hematoma following spinal manipulative therapy: case report and review of the literature. Clin Neurol Neurosurg 2011;113:575–7. 10. Binnert D, Thierry A, Michiels R, Soichot P, Perrin M. Presentation of a new case of spontaneous spinal extradural hematoma observed during labor. [Article in French] J Med Lyon 1971;52:1307–9. 11. Braun P, Kazmi K, Nogués-Meléndez P, Mas-Estellés F, Aparici-Robles F. MRI findings in spinal subdural and epidural hematomas. Eur J Radiol 2007;64:119–25.

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Akar et al. Acute spinal epidural hematoma 12. Akgün B, Sürme MB, Öztürk S, Erol FS. Spontan Spinal Epidural Hematomlar: 12 Olgunun Değerlendirilmesi. FÜ Sağ Bil Tıp Derg 2016;30:107−11. 13. Bakker NA, Veeger NJ, Vergeer RA, Groen RJ. Prognosis after spinal cord and cauda compression in spontaneous spinal epidural hematomas.

Neurology 2015;84:1894–903. 14. Ryu JI, Han MH, Kim JM, Kim CH, Cheong JH. Cervical Epidural Hematoma That Induced Sudden Paraparesis After Cervical Spine Massage: Case Report and Literature Review. World Neurosurg 2018;112:217– 20.

OLGU SUNUMU - ÖZET

Akut spinal epidural hematom: Olgu sunumu ve literatürün gözden geçirilmesi Dr. Ezgi Akar,1 Dr. Ahmet Öğrenci,2 Dr. Orkun Koban,2 Dr. Mesut Yılmaz,3 Dr. Sedat Dalbayrak2 1 2 3

Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul Okan Üniversitesi Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, İstanbul Nörospi̇ nal Akademi̇ , Beyin ve Sinir Cerrahisi Kliniği, İstanbul

Spinal epidural hematom (SEH) omurilik basısı ve nörolojik defisit gelişiminin nadir fakat önemli bir sebebidir. Etyoloji genellikle bilinmez ve acil cerrahi müdahele gerektirir. Bu çalışmada amacımız, nadir bir olgu sunumu ile travmatik SEH’nin klinik önemi, tedavi stratejileri ve tedavi sonrası son durumlarını gözden geçirmektir. Olgumuz 42 yaşında kadın hasta olup, sırt ağrısı, bacaklarda his ve kuvvet kaybı ile başvurdu. Hastanın herhangi bir hastalığı yoktu ve antikoagülan ilaç kullanımıyordu. Hasta, ara sıra olan sırt ağrısından dolayı geleneksel sırt masajı yaptırdıktan yarım saat sonra bacaklarında uyuşma ve kuvvet kaybı ile başvurdu. Hasta kliniğimizde görüldüğünde paraplejik ve T4 altında anestezik idi. Torakal bilgisayarlı tomografi (BT) ve manyetik rezonans görüntülerde (MRG) T3-T4 seviyelerinde posteriyor epidural akut hemoraji izlendi. On ikinci saatte, acil dekompresif hemilaminektomi işlemi yapılarak hematom boşaltıldı. Ameliyat sonrası 24. saatte hastada semptomatik iyileşme görüldü ve altıncı ayda hasta destekle mobilize oluyordu. SEH, ani başlayan sırt ağrısı ve ekstremite güçsüzlüğü olan olgularda akla gelmesi gereken nadir bir durumdur. Tanıda altın standart inceleme MRG olmakla beraber, cerrahi müdahaleyi geciktirmemek için BT çoğu zaman yeterli olabilmektedir. Tanısı koyulan ve nörolojik defisiti olan olgularda acil cerrahi dekompresyon (laminektomi/hemilaminektomi) yapılmalıdır. Anahtar sözcükler: Dekompresif cerrahi; hemilaminektomi; manyetik rezonans görüntüleme; spinal epidural hematom. Ulus Travma Acil Cerrahi Derg 2020;26(4):628-631

doi: 10.14744/tjtes.2019.60956

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CA S E R EP O RT

A rarely encountered case: A neuroendocrine tumor in strangulated Littre’s hernia Ahmet Erdoğan, M.D.,1

Akın Bostanoğlu, M.D.2

Department of General Surgery, Kahramanmaraş Elbistan State Hospital, Kahramanmaraş-Turkey

Department of General Surgery, Ankara Numune Training and Research Hospital, Ankara-Turkey

ABSTRACT Littre’s hernia is a rare condition that involves Meckel’s diverticulum in the hernia sac. Meckel’s diverticulum is the true diverticulum of the small intestine. Neuroendocrine tumors may develop in it; however, there are very few reported cases. In this study, we present a case of neuroendocrine tumor in strangulated Littre’s hernia, on which we did not find a study when we reviewed the relevant literature. A 71-year-old male patient presented to our outpatient clinic with complaints of left groin pain and swelling in the groin. Acute abdomen findings were also present in the abdominal examination of the patient. The patient was operated on immediately and it was observed during the operation that the herniated Meckel’s diverticulum was perforated. Segmental small intestine resection was performed. The pathology results of the patient revealed a well-differentiated neuroendocrine tumor with mucosal and submucosal localization in Meckel’s diverticulum. We believe that if Meckel’s diverticulum is found in the hernia sac in incarcerated hernias, it must be completely resected as a neuroendocrine tumor may develop, even if only rarely. Keywords: Littre’s hernia; Meckel’s diverticulum; neuroendocrine tumor.

INTRODUCTION

CASE REPORT

Littre’s hernia is a rare condition that involves Meckel’s diverticulum (MD) in the hernia sac, which was first described by the French surgeon Alexis de Littre in 1700.[1] MD is the true diverticulum of the small intestine that is formed as a result of the incomplete obliteration of the omphalomesenteric (vitelline) duct, and it occurs in approximately 1% to 3% of people.[2] Approximately 4% of the cases may develop complications requiring surgical or medical treatment, which include gastrointestinal bleeding and obstruction, diverticulitis, and perforation. Benign and malignant tumors can also be observed due to the presence of heterotopic mucosa in the diverticulum.[3] In the literature, there are a limited number of cases of neuroendocrine tumors (NETs) in MD. We present a case of a NET in strangulated Littre’s hernia. To our knowledge, this is the first case of a NET in strangulated Littre’s hernia in the literature.

A 71-year-old male patient presented to our outpatient clinic with complaints of left groin pain and swelling in the groin. It was found that the patient was experiencing groin pain for two days and had no gas or stool output for 24 hours. As a result of physical examination, it was revealed that the patient had a left incarcerated inguinal hernia. Abdominal examination revealed rebound, defense, and distension. The patient’s medical history revealed that he was recently diagnosed with pneumonia and his treatment was ongoing. Blood tests revealed leukocytosis in the hemogram [white blood cell count: 11.9×103/µL (reference range: 4.8–10.8)]. Biochemical values revealed that urea and creatinine levels were high [urea: 125 mg/dL (17–43), creatinine: 2.01 mg/dL (0.81–1.44)]. There was an air-fluid level on the abdominal X-ray (Fig. 1). Abdominal ultrasonography (USG) showed dilatation of small intestine segments and small intestine wall thickening and the presence

Cite this article as: Erdoğan A, Bostanoğlu A. A rarely encountered case: A neuroendocrine tumor in strangulated Littre’s hernia. Ulus Travma Acil Cerrahi Derg 2020;26:632-634. Address for correspondence: Ahmet Erdoğan, M.D. Kahramanmaraş Elbistan Devlet Hastanesi, Genel Cerrahi Kliniği, Kahramanmaraş, Turkey Tel: +90 344 - 413 80 01 E-mail: erdogannumune@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):632-634 DOI: 10.14744/tjtes.2019.30378 Submitted: 22.11.2018 Accepted: 29.07.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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and submucosal localization in MD; the surgical margins were intact and no mitosis was found. As a result of the immunohistochemical analysis, it was reported that widespread positive staining with chromogranin and synaptophysin was present in the tumor cells, and the Ki-67 proliferation index was around 1%. Patient consent was obtained for this study.

DISCUSSION Meckel’s diverticulum is the true diverticulum that holds the entire layer of the small intestine. It is usually located in 45-90 cm proximal to the ileocecal valve. In the literature, diverticula of 1–56 cm in length and 1-50 cm in width have been reported.[4] In this case, MD was located approximately 120 cm proximal to the ileocecal valve. In the pathology report, the diverticulum length was reported to be 3 cm, and the diameter was 2 cm. MD includes ectopic mucosal areas, especially of the gastric type. Benign lesions, such as lipoma and leiomyoma, or malignant proliferative-type lesions, such as adenocarcinoma, malignant sarcoma, and often carcinoid tumors may develop here.[5] In this case, a NET was observed in MD. Carcinoid tumors in MD are about 2.5 times more common in males than females. The mean age of onset is 55 years. Five-year tumor-specific survival is 100% in stage I and stage II patients.[6] This patient was male, and his age was 71, compatible with the literature. There was no recurrence in the 48th month of follow-up, and the patient is still alive.

Figure 1. Air-fluid level on the abdominal X-ray. (a)

(b)

Figure 2. (a, b) Perioperative image of the perforated Meckel’s diverticulum.

of fluid between the intestinal loops and the pelvis. Left inguinal USG revealed herniated intestinal loops and fluid in the hernia sac. The patient was operated on with a pre-diagnosis of an acute abdomen due to his herniated intestine. He was operated on under regional anesthesia, as he had pneumonia. There were widespread purulent fluids and intestinal contents in the abdomen. The exploration revealed that the ileum was perforated from the herniated MD into the left internal ring, approximately 120 cm proximal to the ileocecal valve (Fig. 2a, b). The perforated segment was resected, and a double-barreled ileostomy was performed. The left inguinal canal was narrowed and sutured into the abdomen. The patient was discharged on the 7th postoperative day without any complications. As a result of the patient’s pathology, it was reported that there was a well-differentiated NET (WHO 2010, carcinoid/NET G1) with a diameter of 0.3 cm with mucosal

MD is usually asymptomatic. MD often occurs with complications. The MD complication rate is approximately 4%, which include bleeding, infection, and obstruction. The most common causes of obstructions are intussusception, volvulus of the diverticulum, and rarely the penetration of the diverticulum into the hernia sac (Littre’s hernia).[3] Littre’s hernia has been reported in the forms of approximately 50% inguinal, 20% femoral, 20% umbilical, and 10% other hernias. In this case, Littre’s hernia was in the form of a strangulated inguinal hernia. The presence of MD in the incarcerated inguinal hernia sac is only determined perioperatively. It is extremely difficult to preoperatively reveal the presence of MD in the hernia sac.[7] It is also almost impossible to diagnose with USG and computed tomography. Imaging methods can be helpful to observe secondary findings, such as the presence of fluid in the hernia sac and bowel wall thickening.[8] In this case, the presence of MD in the hernia sac was found during the operation. Preoperative USG revealed the presence of bowel loops and fluid in the hernia sac, but MD was not revealed.

Table 1. 2010 WHO classification of the neuroendocrine neoplasms

Grade

Mitotic count (10 HPF)

Ki 67 index

Well-differentiated neoplasms

NET G1

≤2%

NET G2

2–20

3–20%

NEC G3 (large or small-cell)

>20

>20%

Poorly differentiated neoplasms

HPF: High-Power Field; NEC: Neuroendocrine Carcinoma; NET: Neuroendocrine Tumor; WHO: World Health Organization.

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In the presence of symptomatic MD and incarcerated Littre’s hernia, the treatment is surgery. The treatment is simple diverticulectomy or the resection of the segmentary small intestine that includes the diverticulum and, in the presence of a hernia, herniorrhaphy. The surgical removal of MD is recommended, as it contains ectopic mucosa, and there is a risk of bleeding.[1,2] There is no special algorithm recommended for NETs in MD in NET guidelines. In recent studies, it has been reported that the prognosis of NETs in MD is similar to that of ileal tumors. If the diameter of the tumor in MD is higher than 1 cm, segmentary small intestine resection is recommended; however, if the tumor diameter is smaller than 1 cm, diverticulectomy is reported to be sufficient.[9] In the current guidelines for ileum and jejunum NETs of the European Neuroendocrine Tumor Society (ENETS), resection with intact surgical margins and lymph node dissection through the mesenteric artery is recommended for nonmetastatic NETs. [10] In this case, MD penetrated the hernia sac and was perforated; therefore, a resection, including the diverticulum, was performed. The postoperative pathology revealed that the tumor diameter in MD was 0.3 cm, and the surgical margins were intact. There was no need for a secondary operation. There have been many classifications on neuroendocrine tumors. To provide consensus on this issue, the World Health Organization (WHO) classified the tumors in accordance with the proliferative activity on 2010 (Table 1).[11] The pathology result of this case revealed a well-differentiated Grade 1 NET according to the 2010 classification of WHO. The interesting part of this case is that cases of incarcerated Littre’s hernia or NETs in MD have been reported in the literature, but we have not encountered any case of a NET in incarcerated Littre’s hernia in our literature review. In conclusion, patients with suspected strangulation should be operated on immediately. If MD is detected in the hernia sac, we believe that it should be completely resected, as aNET can be observed in the ectopic tissue, even if only rarely. Informed Consent: Written informed consent was ob-

tained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.E., A.B.; Design: A.E., A.B.; Supervision: A.B.; Fundings: A.E., A.B.; Materials: A.E.; Data: A.E.; Analysis: A.B.; Literature search: A.E.; Writing: A.E.; Critical revision: A.B. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Skandalakis PN, Zoras O, Skandalakis JE, Mirilas P. Littre hernia: surgical anatomy, embryology, and technique of repair. Am Surg 2006;72:238–43. 2. Horkoff MJ, Smyth NG, Hunter JM. A large incarcerated Meckel’s diverticulum in an inguinal hernia. Int J Surg Case Rep 2014;5:899–901. 3. Lequet J, Menahem B, Alves A, Fohlen A, Mulliri A. Meckel’s diverticulum in the adult. J Visc Surg 2017;154:253–9. 4. Malik AA; Shams-ul-Bari, Wani KA, Khaja AR. Meckel’s diverticulumRevisited. Saudi J Gastroenterol 2010;16:3–7. 5. Caracappa D, Gullà N, Lombardo F, Burini G, Castellani E, Boselli C, et al. Incidental finding of carcinoid tumor on Meckel’s diverticulum: case report and literature review, should prophylactic resection be recommended? World J Surg Oncol 2014;12:144. 6. Mora-Guzmán I, Muñoz de Nova JL, Martín-Pérez E. Neuroendocrine tumours within a Meckel’s diverticulum. Ann R Coll Surg Engl 2018;100:e10–1. 7. Mirza MS. Incarcerated Littre’s femoral hernia: case report and review of the literature. J Ayub Med Coll Abbottabad 2007;19:60–1. 8. Citgez B, Yetkin G, Uludag M, Karakoc S, Akgun I, Ozsahin H. Littre’s hernia, an incarcerated ventral incisional hernia containing a strangulated meckel diverticulum: report of a case. Surg Today 2011;41:576–8. 9. Escarrà JM, Fraccalvieri D, Paules Villar MJ, Kreisler Moreno E. Neuroendocrine tumor in Meckel’s diverticulum: An unusual finding. Cir Esp 2015;93:e135–6. 10. Niederle B, Pape UF, Costa F, Gross D, Kelestimur F, Knigge U, et al; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for Neuroendocrine Neoplasms of the Jejunum and Ileum. Neuroendocrinology 2016;103:125−38. 11. Rindi G, Arnold R, Bosman FT. Nomenclature and classification of neuroendocri neoplasms of the digestive system. In: Bosman TF, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: International Agency for Research on cancer (IARC); 2010.p.13.

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Nadir görülen bir olgu: Strangüle Littre hernisi içerisinde nöroendokrin tümör Dr. Ahmet Erdoğan,1 Dr. Akın Bostanoğlu2 1 2

Kahramanmaraş Elbistan Devlet Hastanesi, Genel Cerrahi Kliniği, Kahramanmaraş Ankara Numune Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

Littre hernisi, fıtık kesesi içerisinde, Meckel divertikülünün olduğu nadir bir durumdur. Meckel divertikülü ise ince bağırsağın gerçek divertikülüdür. İçerisinde nöronendokrin tümör gelişebilir, ancak bildirilen olgu sayısı azdır. Bu yazıda, literatür taramasında hiç rastlamadığımız, strangüle Littre hernisi içerisinde nöroendokrin tümörün olduğu bir olgu sunduk. 71 yaşında erkek hasta, sol kasık ağrısı ve kasıkta şişlik şikayeti ile polikliniğimize başvurdu. Aynı zamanda hastanın karın muyanesinde akut karın bulguları mevcuttu. Hasta acil ameliyat edildi, operasyonda herniye olmuş Meckel divertikülünün perfore olduğu izlendi. Segmenter ince bağırsak rezeksiyonu yapıldı. Hastanın patoloji sonucunda; ince bağırsaktaki Meckel divertikülü içerisinde mukoza ve submukoza yerleşimli iyi diferansiye nöroendokrin tümör izlendi. İnkarsere hernilerde, herni kesesi içerisinde Meckel düvertikülü saptanırsa, çok nadir de olsa nöroendokrin tümör görülebileceğinden tamamen rezeke edilmesi gerektiğini düşünmekteyiz. Anahtar sözcükler: Littre hernisi; Meckel divertikülü; nöroendokrin tümör. Ulus Travma Acil Cerrahi Derg 2020;26(4):632-634

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Failed angioembolization of a ruptured liver hemangioma complicated by iatrogenic injury of subclavian vein during catheter insertion Wu Seong Kang, M.D.,1

Young Goun Jo, M.D.,2

Yun Chul Park, M.D.2

Department of Trauma Surgery, Wonkwang University Hospital, Iksan-Korea

Division of Trauma Surgery, Department of Surgery, Chonnam National University Hospital and Medical School, Gwangju-Korea

ABSTRACT In this study, we report a case of failed angioembolization of a ruptured liver hemangioma complicated by iatrogenic injury of the subclavian vein during catheter insertion. A 30-year-old woman experienced blunt trauma upon falling from her bed. Laceration of a seemingly preexisting hepatic hemangioma was diagnosed. No other injury was detected during a preoperative diagnostic workup. Subclavian vein catheterization was performed, followed by angioembolization to control bleeding due to the ruptured hemangioma. After angioembolization, the patientâ&#x20AC;&#x2122;s systolic blood pressure and hemoglobin levels were 70 mmHg and 5.3 g/dL, respectively. She underwent emergency laparotomy. During the surgery, a large volume of blood in the abdominal cavity due to profuse bleeding from the ruptured hemangioma was observed. Because of a hemothorax found on chest radiography, we performed thoracoscopy, which revealed a large volume of blood in the right thoracic cavity and perforation of the subclavian vein by the catheter. After the damage-control surgery, the patient recovered safely. In this case, ruptured liver hemangioma complicated by subclavian vein catheter-related injury was treated safely using damage-control surgery. The catheter-related injury could be identified and treated using thoracoscopy. Keywords: Catheter; hemorrhage; injuries; liver; subclavian.

INTRODUCTION

CASE REPORT

For hemodynamically unstable trauma patients, central venous catheterization is used to achieve sufficient resuscitation. The subclavian vein is a common route used for the central line. However, central venous catheterization may cause complications ranging from mild to severe.[1] Especially, mechanical complications of subclavian catheterization, such as hemothorax or pneumothorax, may aggravate other injuries in the acute stage of severe trauma, and these complications may result in deterioration of the clinical course.

A 30-year old woman was admitted to our emergency room (ER) with a referral from another hospital. She experienced blunt trauma upon falling from her bed and was injured by hitting a dumbbell on the floor at her home. Upon arrival, her systolic blood pressure (SBP) was 50 mmHg, and after crystalloid fluid resuscitation, her SBP increased immediately to 100 mmHg. Her initial blood hemoglobin was 8.8 g/ dL, and arterial blood gas analysis (AGBA) revealed a pH of 7.26. A computed tomography (CT) scan had already been performed at the previous hospital and hepatic hemangioma laceration (1.5 cm in segment 8) with perihepatic hemoperitoneum was diagnosed (Fig. 1a). The hemangioma appeared to have been preexisting. There was no abdominal tender-

In this study, we report a case of failed angioembolization of a ruptured liver hemangioma complicated by iatrogenic injury of the subclavian vein during catheter insertion.

Cite this article as: Kang WS, Jo YG, Park YC. Failed angioembolization of a ruptured liver hemangioma complicated by iatrogenic injury of subclavian vein during catheter insertion. Ulus Travma Acil Cerrahi Derg 2020;26:635-638. Address for correspondence: Young Goun Jo, M.D. 42, Jebong-ro, Dong-gu, Gwangju, 61469, Korea Gwangju, South Korea Tel: +82 62-220-6456 E-mail: thinkjo82@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):635-638 DOI: 10.14744/tjtes.2019.04343 Submitted: 13.01.2019 Accepted: 05.08.2019 Online: 24.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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ness on physical examination. No other injury was detected during a preoperative diagnostic workup. In the ER, subclavian vein catheterization was performed for effective resuscitation, and chest radiography was checked to identify the indwelling catheter and complications, such as pneumothorax and hemothorax (Fig. 2b). Subsequently, angioembolization successfully controlled the bleeding of the hemangioma laceration (Fig. 1b). After angioembolization, the patient was admitted to the intensive care unit (ICU). However, 30 minutes after the angioembolization, the patient’s SBP and blood hemoglobin decreased to 70 mmHg and 5.3 g/dL. Additionally, her abdomen was distended and a newly developed hemothorax was found on chest radiography (Fig. 2c). An emergency reoperation was immediately performed. After laparotomy, a large volume of blood in the abdominal cavity due to profuse bleeding from ruptured hemangioma was observed. Trocars were inserted into the right chest wall to identify the cause of the hemothorax. During thoracoscopy, a large volume of blood in the right thoracic cavity was seen and perforation

(a)

(b)

of the subclavian vein by the catheter was found (Fig. 3). As the ongoing bleeding of the ruptured hemangioma was found, pad compression of the liver to control the bleeding was performed with temporary abdominal closure (Fig. 4). After the removal of the subclavian vein catheter, there was no bleeding from the subclavian vein. The injured subclavian vein remained without any additional suture or ligation. An additional catheter was inserted via the right internal jugular vein. A thoracostomy tube was also inserted into the right thoracic cavity via a trocar site (Fig. 2d). Transfusion of 16 units of packed red blood cells and eight units of fresh frozen plasma was performed during the operation. Two days after the first laparotomy, a second operation was performed, the pad was removed, and the patient’s abdomen was closed. The chest tube was removed on postoperative day nine. The patient recovered well and was discharged on the postoperative day 12. patient’s consent was obtained for this study.

DISCUSSION In this era of damage-control laparotomy, damage control is regarded as the most effective strategy to treat coagulopathy and prevent a vicious cycle of the hemorrhagic shock. [2] Although the term “damage control” was first coined in 1993 by Rotondo et al.,[3] the concept of abbreviated surgery followed by a secondary definitive operation for major liver trauma was already tried in 1979.[4] Recently, perihepatic packing has been the most widely used and suc-

Figure 1. (a) Abdominal computed tomography scan showed ruptured hepatic hemangioma (red arrow) with hemoperitoneum. (b) Angiography showed hepatic hemangioma (red arrow).

(a)

(c)

(b)

(d)

Figure 3. The red arrow is pointing to the catheter, which is seen protruding into the thoracic cavity via the venous wall, identified during thoracoscopy.

(a)

Figure 2. (a) Chest X-ray (CXR) at the time of admission. (b) CXR after right subclavian venous catheterization seemed to show catheter tip (red arrow) in normal position. (c) CXR after angioembolization showed hemothorax (red arrow). (d) CXR after the first operation with thoracoscopy showed an indwelling chest tube (red arrow). The right subclavian venous catheter was removed.

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(b)

Figure 4. (a) Pad packing (red arrow) with temporary abdominal closure was performed in the first operation. (b) No bleeding from the ruptured hepatic hemangioma occurred during the second operation.

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cessful method for the surgical management of blunt hepatic trauma.[5] In most cases, the cause of the uncontrolled hepatic hemorrhage is the trauma itself. In the present case, although the ruptured hemangioma was initially treated successfully using interventional radiology, failed angioembolization with the iatrogenic injury that arose from the subclavian vein catheter aggravated the coagulopathy. Damage-control laparotomy with hepatic pad packing was used to control bleeding because suture hemostasis or liver resection may cause additional bleeding in a patient with coagulopathy. It is a unique situation in that a lower-energy trauma-induced rupture of hepatic hemangioma. Additionally, the clinical deterioration that arises from the subclavian catheter injury was also uncommon. The initial chest radiography appeared completely normal and did not reveal a pneumothorax or hemothorax. Thoracoscopy, however, revealed the catheter tip penetrating into the thoracic cavity using the subclavian venous lumen, allowing transfused blood and fluid to accumulate in the thoracic cavity. Mechanical complications (such as arterial puncture, hematoma, and pneumothorax) of central venous catheterization are reported to occur in 5% to 19% of patients, and infectious and thrombotic complications are reported to occur in 5% to 26% and 2% to 25% of patients, respectively. [1] The mechanical complications are reported to be similar to whether catheterization is performed using the internal jugular or the subclavian route.[1] In the prospective randomized trial of subclavian vein catheterization by Mansfield et al.,[6] the complications included misplacement, arterial puncture, pneumothorax, and mediastinal hematoma. In another prospective randomized trial by Merrer et al.,[7] no major hematoma or hemothorax occurred in the subclavian vein catheterization group. In a case report by Haaverstad et al.,[8] it was reported that a right subclavian catheter perforated the aorta, resulting in sudden cardiac tamponade. However, to our knowledge, there is no report similar to the present case. In the present case, thoracoscopy during the operation was performed to evaluate the hemothorax. If the thoracoscopy had not been done, it would have been difficult to identify the penetration of the catheter into the thoracic cavity. Liver hemangiomas are the most common benign liver tumors and may grow up to 20 cm.[9] In autopsies, the incidence of liver hemangiomas is reported from 0.4% to 7.3%. [9] In a recent large retrospective cross-sectional study about the prevalence and clinical outcome of a hepatic hemangioma that analyzed 83,181 patient records,[10] the prevalence of hepatic hemangioma was 2.5% and spontaneous bleeding occurred in only five patients (0.47%). Additionally, all patients with spontaneous bleeding had a giant hemangioma (>4 cm in diameter).[10] In the present case, the size of the heman-

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gioma was only 1.5 cm and a low-energy injury was suspected because she had fallen from the bed. Because of the small size of the hemangioma in the present case, perihepatic pad packing without resection appeared to be sufficient treatment and no additional sign of bleeding was found after the second operation. In the literature,[9,10] it was reported that arterial embolization and surgical resection are available for ruptured hemangiomas. However, to our knowledge, there is a lack of evidence regarding damage-control laparotomy for a ruptured hemangioma. In conclusion, the subclavian vein catheter penetrated into the thoracic cavity via the subclavian venous wall, which contributed to the failure to correct the coagulopathy. The patient was successfully treated using damage-control surgery with thoracoscopy. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Conflict of Interest: None declared.

REFERENCES 1. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med 2003;348:1123–33. 2. Ball CG. Damage control surgery. Curr Opin Crit Care 2015;21:538–43. 3. Rotondo MF, Schwab CW, McGonigal MD, Phillips GR 3rd, Fruchterman TM, Kauder DR, et al. ‘Damage control’: an approach for improved survival in exsanguinating penetrating abdominal injury. J Trauma 1993;35:375−82; discussion 382−3. 4. Calne RY, McMaster P, Pentlow BD. The treatment of major liver trauma by primary packing with transfer of the patient for definitive treatment. Br J Surg 1979;66:338–9. 5. Kozar RA, Feliciano DV, Moore EE, Moore FA, Cocanour CS, West MA, et al. Western Trauma Association/critical decisions in trauma: operative management of adult blunt hepatic trauma. J Trauma 2011;71:1−5. 6. Mansfield PF, Hohn DC, Fornage BD, Gregurich MA, Ota DM. Complications and failures of subclavian-vein catheterization. N Engl J Med 1994;331:1735–8. 7. Merrer J, De Jonghe B, Golliot F, Lefrant JY, Raffy B, Barre E, et al; French Catheter Study Group in Intensive Care. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286:700−7. 8. Haaverstad R, Latto PN, Vitale N. Right subclavian catheter perforation of the aorta due to an incorrect external landmark-guided insertion technique. CJEM 2007;9:43–5. 9. Donati M, Stavrou GA, Donati A, Oldhafer KJ. The risk of spontaneous rupture of liver hemangiomas: a critical review of the literature. J Hepatobiliary Pancreat Sci 2011;18:797–805. 10. Mocchegiani F, Vincenzi P, Coletta M, Agostini A, Marzioni M, Baroni GS, et al. Prevalence and clinical outcome of hepatic haemangioma with specific reference to the risk of rupture: A large retrospective cross-sectional study. Dig Liver Dis 2016;48:309−14.

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OLGU SUNUMU - ÖZET

Kateter yerleştirilmesi sırasında subklavyen venin iyatrojenik yaralanması ile komplike olan rüptüre karaciğer hemanjiyomunun başarısız anjiyoembolizasyonu Dr. Wu Seong Kang,1 Dr. Young Goun Jo,2 Dr. Yun Chul Park2 1 2

Wonkwang Üniversite Hastanesi, Travma Cerrahisi Kliniği, Iksan-Kore Chonnam Ulusal Üniversite Hastanesi ve Tıp Fakültesi, Cerrahi Anabilim Dalı, Travma Cerrahisi Bölümü, Gwangju-Kore

Biz kateter takılması sırasında subklavyen venin iyatrojenik yaralanması ile komplike rüptüre bir karaciğer hemanjiyomunun başarısız anjiyoembolizasyonu olgusunu sunuyoruz. Otuz yaşında bir kadın yatağından düştüğünde künt travmaya maruz kalmış. Önceden var olduğu görünen hepatik bir hemanjiyomun laserasyonu teşhis edildi. Ameliyat öncesi tanısal incelemeleri sırasında başka bir yaralanma tespit edilmedi. Subklavyen ven kateterizasyonu ve ardından rüptüre hemanjiyom nedeniyle oluşan kanamayı kontrol etmek için anjiyoembolizasyon yapıldı. Anjiyoembolizasyondan sonra hastanın sistolik kan basıncı ve hemoglobin düzeyi sırasıyla 70 mmHg ve 5.3 g/dL idi. Acil laparotomi yapıldı. Ameliyat sırasında, rüptüre hemanjiyomdan abondan kanama nedeniyle karın boşluğunda büyük miktarda kan gözlendi. Göğüs radyografisinde hemotoraks bulgusu nedeniyle uygulanan torakoskopi sağ toraks boşluğunda büyük miktarda kan olduğunu ve subklavyen venin kateter tarafından delinmiş olduğunu gösterdi. Hasar kontrol cerrahisinden sonra hasta güvenli bir şekilde iyileşti. Bu olguda, subklavyen ven kateteri ile ilişkili yaralanma ile komplike olan rüptüre karaciğer hemanjiyomu hasar kontrol cerrahisi ile güvenli bir şekilde tedavi edildi. Kateterle ilişkili yaralanma torakoskopi kullanılarak tanımlanabilir ve tedavi edilebilir. Anahtar sözcükler: Kanama; karaciğer; kateter; subklavyen; yaralanma Ulus Travma Acil Cerrahi Derg 2020;26(4):635-638

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Fallopian tube herniation from trocar-site after laparoscopic appendectomy Anıl Ergin, M.D., Yalın İşcan, M.D., Birol Ağca, M.D., Bora Karip, M.D., Kemal Memişoğlu, M.D. Department of General Surgery, University of Health Sciences, İstanbul Fatih Sultan Mehmet Training and Research Hospital, İstanbul-Turkey

ABSTRACT Trocar site hernias are a type of incisional hernias and may occur within a variable time shift after surgery. A mean incidence of 1.85% was reported, and the first trocar site hernia was narrated by Maio et al. in 1991 describing small bowel obstruction due to trocar site herniation after laparoscopic cholecystectomy.The 10-mm-trocar port is more frequently problematic, and a trocar site hernia in 5 mm port is very rare. This report unveils a 5mm trocar site herniation of right fallopian tube following laparoscopic appendectomy. In this case study, a 19-year-old female patient applied to the emergency department because of a discharge in the right lower quadrant was reported. She explained that she had undergone laparoscopic appendectomy two days before and discharged the next day uneventfully. The surgical report described a suction drain in the right lower quadrant where the patient was suffering from the discharge. The physical examination revealed no tenderness, but an abdominal CT disclosed an edematous tubular structure herniating from the 5 mm trocar site where the drain was put. She was re-operated laparoscopically due to early trocar site hernia, and the right fallopian tube was observed herniating through the defect. After the reduction into the abdomen, the fallopian tube was observed fine, and the defect was closed using 2/0 polypropylene suture.Trocar site hernias are rare but may cause serious complications after laparoscopic surgery. They may occur early after the surgery, but the time shift is variable. Although mechanical bowel obstructions are more frequent endpoint, it should be remembered that any organ within the abdominal cavity may herniate. Keywords: Fallopian tube; laparoscopic appendectomy; trocar site hernia.

INTRODUCTION After abdominal surgery, negative features, such as pain, wound infection and development of the incision hernia, are less common in laparoscopy compared to open surgery. [1] The laparoscopic approach offers advantages, such as low blood loss, short hospital stay and early return to work.[2] Besides, laparoscopic surgery may cause complications, such as vascular injuries, bowel injuries, nerve damage and incisional hernia.[3] The definition of trocar site hernias is used for incisional hernias formed after laparoscopic surgery, or trocar site hernias are rare complications. The incidence is between 1% and 6%. When the literature is reviewed, trocar site hernia is most commonly seen in 10 mm trocar sites.[4] Many

surgeons do not repair the trocar sites of 5 mm because a hernia will not be developed from this size of the defect.[5] In this case report, a case in which the detection of fallopian tube herniation in a 5 mm trocar site in a patient who had undergone laparoscopic appendectomy was presented.

CASE REPORT In the physical examination of a 19-year-old female patient, who was discharged on the first postoperative day after the laparoscopic appendectomy and applied to Emergency Room with a complaint of drainage in the right lower quadrant and appearance of fatty tissue on the postoperative second day, an edematous fatty tubular structure that cannot be reduced

Cite this article as: Ergin A, İşcan Y, Ağca B, Karip B, Memişoğlu K. Fallopian tube herniation from trocar-site after laparoscopic appendectomy. Ulus Travma Acil Cerrahi Derg 2020;26:639-641. Address for correspondence: Anıl Ergin, M.D. Sağlık Bilimleri Üniversitesi, İstanbul Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 216 - 578 30 00 E-mail: dranilergin@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):639-641 DOI: 10.14744/tjtes.2019.72461 Submitted: 21.11.2018 Accepted: 30.07.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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at the port entrance site of the right lower quadrant and serosal drainage from this structure was observed (Fig. 1). Acute abdomen findings were not observed in the abdominal examination. In laboratory values, hemoglobulin: 12.3 gr/ dl white blood cell: 14.2x103 /UL, C-reactive protein: 4 mg/ dl. In the retrospective examination of the patient, it was learned that the patient underwent laparoscopic appendectomy for perforated appendicitis was inserted an aspiration drain to her Douglas space from the 5-mm trocar site in the right lower quadrant, and it was removed in the second day after the operation. In the computed tomography taken in the emergency room, a tubular structure with an edematous appearance, which is herniated from the 5 mm trocar site in the right lower quadrant, was identified (Fig. 2). With the consideration of an early trocar site herniation, the patient underwent a laparoscopic exploration intended surgery. During exploration, the right fallopian tube was seen, which was herniated from a 5 mm trocar site (Fig. 3). After the fallopian tube was rejected into the abdomen, the defect area was repaired with the endoclose, with the help of a transfacial 2.0

Figure 1. Fatty tissue in the trocar site.

Figure 2. Tubular structure with an edematous appearance in the computed tomography.

polypropylene suture. The patient, who had no postoperative complications, was discharged on the first postoperative day. Patientâ&#x20AC;&#x2122;s consent was obtained for this study.

DISCUSSION Compared to open surgery, laparoscopic surgery has become a more preferred method in a wide area. The advantages, such as pain, rapid recovery and low incisional hernia rate, are ensuring to be more preferred.[1] However, it has been known since 1967 that laparoscopic surgery may also cause trocar site hernias.[6] Several risk factors have been identified in the literature regarding the trocar site hernia. Trocar size and location, finding the pre-existing facial defects, expanding the trocar insertion site to remove the specimen, high blood glucose levels, obesity, increased intra-abdominal pressure due to chronic obstructive pulmonary diseases are some of these risk factors. However, the most effective among these risk factors was determined as trocar size. The hernia rates developed from 12 mm and 10 mm trocar sites are significantly higher than the ones developed from 5 mm and 3 mm trocar sites.[7] Thus, Sanz-LĂłpez et al.[8] have recommended the repair of trocar insertion site defects larger than 5 mm. It is recommended that 5-mm trocar sites should only be closed in cases where the port site is manipulated for various reasons.[9] Another important issue in the prevention of postoperative trocar site hernia is trocar insertion sites. Trocars inserted from the midline (especially the trocar inserted from the umbilical area) are the most common sites of herniation. [7] The reason for this is thought to be the presence of fascia as a single leaf at Linea Alba align, and the presence of a natural defect area, such as umbilicus. In the literature, review of Ben-Shian Huang et al.,[10] only one case in which the fallopian tube was herniated from 5-mm trocar was found. A 9-year-old boy who underwent laparoscopic cystectomy was admitted to the emergency room with complaints of pain on the left lower quadrant and a palpable mass in the trocar site in the lower left quadrant on the seventh postoperative day. In this case, laparotomy was preferred for the treatment, and fallopian tube excision was performed.[111] In our case, although there was no risk factor for the development of trocar site herniation, a 5-mm trocar site hernia was developed. Therefore, it should be kept in mind that there may be herniation from a 5 mm trocar sites without any risk factors, and herniation of the abdominal organs from these defect sites is possible. This case report is the first 5 mm trocar site fallopian tube herniation case treated laparoscopically.

Conclusion

Figure 3. Herniated right fallopian tube in 5 mm trocar site.

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Regardless of the size of the trocar, after laparoscopic surgery, trocar site hernias may cause serious early and late complications. Although mechanical intestinal obstruction is typically came to mind in trocar site hernias, it should be kept in mind that any intra-abdominal organ may be herniated from this site. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Ergin et al. Fallopian tube herniation from trocar-site after laparoscopic appendectomy

Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.E.; Design: A.E.; Supervision: Y.İ.; Fundings: Y.İ.; Materials: B.A.; Data: B.K.; Analysis: A.E.; Literature search: A.E.; Writing: A.E.; Critical revision: K.M. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Tan S, Wu G, Zhuang Q, Xi Q, Meng Q, Jiang Y, et al. Laparoscopic versus open repair for perforated peptic ulcer: A meta analysis of randomized controlled trials. Int J Surg 2016;33:124−32. 2. Trejo-Ávila ME, Valenzuela-Salazar C, Betancourt-Ferreyra J, Fernández-Enríquez E, Romero-Loera S, Moreno-Portillo M. Laparoscopic Versus Open Surgery for Abdominal Trauma: A Case-Matched Study.

J Laparoendosc Adv Surg Tech A 2017;27:383–7. 3. Nezhat C, Nezhat F, Seidman DS, Nezhat C. Incisional hernias after operative laparoscopy. J Laparoendosc Adv Surg Tech A 1997;7:111–5. 4. Bunting DM. Port-site hernia following laparoscopic cholecystectomy. JSLS 2010;14:490–7. 5. Agha RA, Fowler AJ, Saeta A, Barai I, Rajmohan S, Orgill DP; SCARE Group. The SCARE Statement: Consensus-based surgical case report guidelines. Int J Surg 2016;34:180–6. 6. Fear RE. Laparoscopy: a valuable aid in gynecologic diagnosis. Obstet Gynecol 1968;31:297–309. 7. Tonouchi H, Ohmori Y, Kobayashi M, Kusunoki M. Trocar site hernia. Arch Surg 2004;139:1248–56. 8. Sanz-López R, Martínez-Ramos C, Núñez-Peña JR, Ruiz de Gopegui M, Pastor-Sirera L, et al. Incisional hernias after laparoscopic vs open cholecystectomy. Surg Endosc 1999;13:922–4. 9. Munro MG. Laparoscopic access: complications, technologies, and techniques. Curr Opin Obstet Gynecol 2002;14:365–74. 10. Huang BS, Seow KM, Tsu KH, Su WH, Lu CH, Wang PH. Small trocar site hernia after laparoscopy. Gynecology and Minimally Invasive Therapy 2013;2:79−84. 11. Wang PH, Yen MS, Yuan CC, Liang SC, Lin JY. Incarcerated hernia in a 5-mm cannula wound. J Am Assoc Gynecol Laparosc 2001;8:449–52.

OLGU SUNUMU - ÖZET

Laparoskopik apendektomi sonrası trokar yerinden fallop tüpü herniasyonu Dr. Anıl Ergin, Dr. Yalın İşcan, Dr. Birol Ağca, Dr. Bora Karip, Dr. Kemal Memişoğlu Sağlık Bilimleri Üniversitesi, İstanbul Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul

Trokar yeri hernisi bir insizyonel herni tipi olup ameliyattan sonra farklı zaman dilimlerinde karşımıza çıkabilmektedir. Ortalama insidansı %1.85 olup ilk kez Maio ve ark. tarafından1991 yılında laparoskopik kolesistektomi sonrası ince bağırsak obstrüksiyonu ile birlikte trokar yeri herniasyonu gelişimini bildirilmiştir. Genellikle 10 mm’lik trokar girişlerinde görülebilen bu durum 5 mm’lik trokar girişlerinde ise nadiren görülmektedir. Bu yazıda, laparoskopik apendektomi sonrasında 5 mm’lik trokar yerinde gelişen, sağ fallop tüpü herniasyonu olgusu sunuldu. On dokuz yaşında kadın hasta, acil polikliniğimize sağ alt kadrandaki insizyon yerinde akıntı ve sağ alt kadran ağrısı şikayetiyle başvurdu. Öyküsünde iki gün önce kliniğimizde akut apandisit tanısı ile laparoskopik apendektomi uygulanmıştı. Ameliyat lojuna bir adet aspiratif dren konarak ameliyat sonlandırıldı. Ameliyat sonrası birinci gün dreni alınıp şifa ile taburcu edildi. Acil poliklinik muayenesinde sağ alt kadrandaki insizyonundan serozal akıntı ve milimetrik yağlı doku evantrasyonu izlenildi. Olguda akut karın bulguları saptanmadı. Akut faz reaktanları normal, yapılan bilgisayarlı tomografide plevik bölgeden sağ alt kadran kesi bölgesine uzanan hidropik tubuler bir yapı izlendi. Bunun üzerine erken dönem gelişen trokar herni ön tanısı ile ameliyata alındı. Laparoskopik eksplorasyonda sağ fallop tüpünün hidropik ve ödemli olduğu ve 5 mm’lik trokar yerine herniye olduğu görüldü. Fallop tüpü laparoskopik olarak redükte edilip batın içerisine alındı. Trokar yerindeki açıklık ise 2/0 prolen ile dikildi. Olgumuz ameliyat sonrası birinci gün şifa ile taburcu edildi. Trokar yeri hernileri laparoskopik cerrahi sonrasında nadir görülmekle birlikte ciddi komplikasyonlardan biridir. Laparoskopik ameliyatlardan sonra erken veya geç dönemlerde gelişebilecek olan bu durumda daha çok mekanik bağırsak tıkanmaları gözüksede diğer intraperitoneal organlarında herniye olabileceği akılda tutulmalıdır. Anahtar sözcükler: Fallop tüpü, laparoskopik apendektomi; trokar yeri hernisi. Ulus Travma Acil Cerrahi Derg 2020;26(4):639-641

doi: 10.14744/tjtes.2019.72461

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CA S E R EP O RT

"Step-by-step" principles of safe laparoscopic approach with technical details in "median arcuate ligament syndrome" Selçuk Gülmez, M.D. Department of Gastroenterological Surgery, University of Health Sciences, Kartal Koşuyolu High Specialized Training and Research Hospital, İstanbul-Turkey

ABSTRACT The median arcuate ligament syndrome (MALS) is a rare cause of postprandial pain and weight loss.The median arcuate ligament (MAL) is a fibrous band of the diaphragmatic crura. Abnormally downward located MAL or high take off of the celiac artery result in external compression the celiac trunk. MAL narrows the truncus coeliacus even more clearly during the expiration.The chronic compression of the celiac artery reduces blood flow and causes symptoms. Symptomatic patients receive surgical treatment, in recent years, an increasing rate, especially laparoscopic.The rate of conversion to open surgery is 10.3% due to vascular injury in hemorrhage, which generally occurs during dissection. A maneuver is needed to continue with the surgical procedure safely here because of the close neighboring of the aorta, truncus coeliacus, and one of its branches. Technical standardization can reduce the complication rate. There is still no standardized and established laparoscopic method in the world. There are no randomized controlled studies in the literature, which show the superiority of these techniques over one another. The maneuver in this case report, through traction with a tape towards caudal, allows a brilliant view on the celiac axis with shortened operation time. It also makes the operation even safer because of its enabling mastery over the celiac artery and easy dissection. Keywords: Celiac artery compression; intestinal angina; median arcuate ligament syndrome.

INTRODUCTION The median arcuate ligament syndrome (MALS), also known as celiac artery compression syndrome, is a rare disease that may cause abdominal pain. MALS was first described by Harjola in 1963, while Dunbar first reported its surgical treatment two years after.[1,2] Minimally invasive procedures have become prominent after 2000 when Roayaie first published a laparoscopic report on MALS,[3] which necessitated symptomatic patients receive surgical treatment.[4] Despite the developments in laparoscopic surgery, the rate of conversion to open surgery is 10.3% due to vascular injury resulting in hemorrhage, which generally occurs during dissection.[5] Experience and technical standardization can reduce the complication rate. The rare occurrence of the disease as case reports prevented gaining experience and answering the

question of which technique is the best. There is still no standardized and established laparoscopic method in the world. There has been an upsurge in the number of publications on the laparoscopic approach recently, and physicians have been trying to standardize the technical details of the procedure in direct proportion to the increase in such reports.[6–8] Median arcuate ligament (MAL) narrows the truncus coeliacus even more clearly during the expiration.[9] Because of that, MAL relaxation is the main goal of surgery. The trend in recent years is to make it laparoscopic. In this case report, we aimed to describe these stages of dissection in steps.

CASE REPORT A 39-year-old male presented with postprandial chronic intermittent epigastric pain, occasional nausea and vomiting for

Cite this article as: Gülmez S. “Step-by-step” principles of safe laparoscopic approach with technical details in “median arcuate ligament syndrome”. Ulus Travma Acil Cerrahi Derg 2020;26:642-646. Address for correspondence: Selçuk Gülmez, M.D. SBÜ Kartal Koşuyolu Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Gastroenteroloji Cerrahi Kliniği, İstanbul, Turkey Tel: +90 216 - 500 1 500 /1358 E-mail: selcukgulmez54@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):642-646 DOI: 10.14744/tjtes.2019.61559 Submitted: 26.07.2019 Accepted: 25.12.2019 Online: 15.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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three years. He had a weight loss of 12 kg in the last four months. He had not any past medical history and his physical examination, laboratory tests, abdomen sonography, esophagogastroscopy, and colonoscopy were normal. However, the magnetic resonance (MR)-Angiography of the abdomen revealed critical stenosis of the celiac axis (Fig. 1). Laparoscopic retrograde MAL-dividing without drain was performed. Subsequently, the patient was free from symptoms and discharged on the 4th postoperative day. He was still symptomfree after 10 months.

The Technical Steps of the Laparoscopic Retrograde Approach Step 1: Anesthesia, patient positioning, trocar placement: Under general anesthesia, the patient was positioned in supine and the 30° reverse Trendelenburg position with open legs. The surgeon will perform the surgery between the legs of the patient. A total of 5 ports were used. The location of the initial 10 mm trocar (30° camera port) was approximately 5 cm above the umbilicus. Then, two 5 mm trocars were placed in the right subcostal region. Laterally of them was as a triangular articulating retractor used. After that, two more 5 mm trocars were placed in the left subcostal region. The two upper trocars were for working and controlled by the surgeon. The left lateral trocar was used for traction of the structures and vascular tape by the first assistant. Step 2: Opening of the hepatogastric ligament (Fig. 2a) and identification and isolation of trifurcation of the celiac trunk (Fig. 2b).

(a)

(b)

Figure 2. (a) Opening of the hepatogastric ligament (1: lymph node 8a, 2: splenic artery, 3: left gastric artery, 4: a. hepatica comm., 5: coronary vein, 6: pancreas). (b) Identification and isolation of trifurcation of the celiac trunk. (a)

Step 3: Passing the vascular tape below the left gastric artery (Fig. 3a) and the A. hepatica communis (Fig. 3b). Step 4: Traction of the intermediate compartment (Fig. 4a) and joining the intermediate compartment with the first part

(b)

Figure 1. Preoperative MR-angiography, critical stenosis of the celiac axis (arrow).

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Figure 3. Passing the vascular tape below the left gastric artery (a) and the A. hepatica communis (b).

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Gülmez et al. “Step-by-step” principles of safe laparoscopic approach with technical details in “MALS” (a)

(b)

Figure 4. (a) Traction of the intermediate compartment. (b) Joining the intermediate compartment with the first part passing below the arteries. MAL marked with asterisks. (a)

(b)

(c)

(d)

Figure 5. (a) Elevation of MAL. Truncus coeliacus marked with asterisks. (b) Clear isolation and visualization of MAL (ca) Cutting the last part of MAL. Trace of the area where MAL narrows the celiac artery root (marked with asterisks). (d) Final image.

passing below the arteries and traction of both components together towards the caudal (Fig. 4b). Extreme traction and abnormal force exerting should be avoided during this traction process. Step 5: Dividing of the musculofibrous structures with the celiac plexus ganglion fibers and lymphatics by using ultrasonic energy devices or hook cautery (Fig. 5a-d).

DISCUSSION MALS is a rare cause of postprandial pain and weight loss brought about by the external compression of the celiac 644

artery that is generally seen in female patients aged between 30 and 50.[10] MAL is a fibrous band of the diaphragmatic crura. Abnormally downward located MAL or high take off of the celiac artery results in external compression celiac trunk.[9] The chronic compression of the celiac artery reduces blood flow and causes symptoms.[11] The pathophysiological mechanism is not yet clear and there is still no consensus. There are two commonly accepted hypotheses about this condition. The first hypothesis is the neurogenic theory, which may arise from direct sympathetic pain or local irritation or indirect splanchnic vasoconstriction brought about by the exterUlus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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nal compression of the celiac artery.[12] The second theory, known as the steal phenomenon, is the gravitation of the current towards the celiac artery using the collaterals between the mesenteric artery and the celiac artery.[2,13] While De Lara argued that the symptoms could be better explained by the neurogenic theory,[12] Glen et al.[2] stated in their review that the steal phenomenon was more commonly accepted by many specialists.

This maneuver, through traction with a tape towards caudal, allows a brilliant view on the celiac axis with shortened operation time. It also makes the operation even safer because of its enabling mastery over the celiac artery and easy dissection.

The symptoms are pronounced, especially during expiration. The murmur in the epigastric area, which becomes especially more prominent during expiration, proves to be a significant clinical finding in the examination of patients.[4]

Peer-review: Internally peer-reviewed.

Diagnostic methods include Doppler ultrasonography, CTor MR-Angiography, and selective catheter angiography.[1] Although selective angiography performed for MALS during inspiration and expiration has been set as the gold standard by some publications,[13] MR-Angiography or CT supported by 3D imaging, which are non-invasive methods, are preferred more frequently today.[1] MAL results in asymptomatic compression at a rate between 10% and 24%[4] and there is no need for intervention in asymptomatic or incidentally detected celiac artery compression.[14] Endovascular and surgical procedures are listed among the treatment options for symptomatic cases. While stents can be placed by percutaneous transluminal angioplasty endovascularly, this intervention does not usually solve the underlying problem of external compression of the celiac body and frequently necessitates surgical intervention. Therefore, the best results in eliminating the symptoms were achieved by celiac decompression.[13] While it was achieved by this open method initially, it is now performed more prominently by minimally invasive methods (laparoscopic or robotic).[2,8,14] There is still no standard surgical technique as this disease is quite rare, studies on the subject are generally limited to case reports, and there are no large case series. Studies in literature generally offer three different surgical techniques. The first surgical technique is the antegrade approach, which is described by the finding of truncus coeliacus by moving downwards from the upper side of the aorta and continuing with this, ending in the decompression of the MAL on the celiac body.[10] The second surgical technique is the retrograde approach within which the left gastric artery and/or the hepatic artery are found, MAL is cut moving upwards, but the upper side of the artery is not dissected.[7] The final surgical technique is a combined technique that simultaneously utilizes both approaches.[6] There are no randomized controlled studies in the literature, which shows the superiority of these techniques over one another. A maneuver is needed to continue with the surgical procedure safely here because of the close neighboring of the aorta, truncus coeliacus, and one of its branches. We, in our case, enabled MAL decompression using a retrograde approach. Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Authorship Contributions: Concept: S.G.; Design: S.G.; Supervision: S.G.; Fundings: S.G.; Materials: S.G.; Data: S.G.; Analysis: S.G.; Literature search: S.G.; Writing: S.G.; Critical revision: S.G. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. A-Cienfuegos J, Rotellar F, Valentí V, Arredondo J, Pedano N, Bueno A, et al. The celiac axis compression syndrome (CACS): critical review in the laparoscopic era. Rev Esp Enferm Dig 2010;102:193−201. 2. Roseborough GS. Laparoscopic management of celiac artery compression syndrome. J Vasc Surg 2009;50:124−33. 3. Roayaie S, Jossart G, Gitlitz D, Lamparello P, Hollier L, Gagner M. Laparoscopic release of celiac artery compression syndrome facilitated by laparoscopic ultrasound scanning to confirm restoration of flow. J Vasc Surg 2000;32:814−7. 4. You JS, Cooper M, Nishida S, Matsuda E, Murariu D. Treatment of median arcuate ligament syndrome via traditional and robotic techniques. Hawaii J Med Public Health 2013;72:279−81. 5. Weber JM, Boules M, Fong K, Abraham B, Bena J, El-Hayek K, et al. Median Arcuate Ligament Syndrome Is Not a Vascular Disease. Ann Vasc Surg 2016;30:22−7. 6. Berard X, Cau J, Déglise S, Trombert D, Saint-Lebes B, Midy D, et al. Laparoscopic surgery for coeliac artery compression syndrome: current management and technical aspects. Eur J Vasc Endovasc Surg 2012;43:38−42. 7. Wani S, Wakde V, Patel R, Potankar R, Mathur SK. Laparoscopic release of median arcuate ligament, J Minim Access Surg 2012;8:16–8. 8. Aday U, Böyük A, Gültürk B, Bozan MB. Safe laparoscopic surgery in median arcuate ligament syndrome. Wideochir Inne Tech Maloinwazyjne 2018;13:539−41. 9. Duran M, Simon F, Ertas N, Schelzig H, Floros N. Open vascular treatment of median arcuate ligament syndrome. BMC Surg 2017;17:95. 10. Lainez RA, Richardson WS. Median arcuate ligament syndrome: a case report. Ochsner J 2013;13:561−4. 11. Hongsakul K, Rookkapan S, Sungsiri J, Tubtawee T. A severe case of median arcuate ligament syndrome with successful angioplasty and stenting. Case Rep Vasc Med 2012;2012:129870. 12. de Lara FV, Higgins C, Hernandez-Vila EA. Median arcuate ligament syndrome confirmed with the use of intravascular ultrasound. Tex Heart Inst J 2014;41:57−60. 13. Kotarać M, Radovanović N, Lekić N, Ražnatović Z, Djordjević V, Lekć D, et al. Surgical treatment of median arcuate ligament syndrome: case report and review of literature. Srp Arh Celok Lek 2015;143:74−8. 14. Tracci MC. Median arcuate ligament compression of the mesenteric vasculature. Tech Vasc Interv Radiol 2015;18:43−50.

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OLGU SUNUMU - ÖZET

“Median arcuate ligament sendromu”nda adım adım teknik detaylarıyla beraber güvenli laparoskopik yaklaşımın ilkeleri Dr. Selçuk Gülmez Sağlık Bilimleri Üniversitesi Kartal Koşuyolu Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Gastroenteroloji Cerrahi Kliniği, İstanbul

Median arkuat ligament sendromu (MALS), yemek yeme sonrası görülen ağrının ve kilo kaybının nadir bir nedenidir. Median arkuat ligament (MAL), diyafragmatik krusların orta kısmındaki fibröz bir banttır. Anormal olarak aşağı doğru yerleşmiş MAL veya çölyak arterin daha kraniyalden çıkması, çölyak gövdenin dıştan basısı ile sonuçlanır. MAL, trunkus çölyakusu özellikle ekspirium sırasında daha da daraltır. Çölyak arterin kronik olarak sıkışması damar içinden geçen kan akışını azaltır ve semptomlara neden olur. Semptomatik hastalar son yıllarda artan oranda daha çok laparoskopik olarak tedavi edilmektedirler. Laparoskopiden açık cerrahiye dönüşüm oranı az olmayıp %10.3’tür, bu da genellikle diseksiyon esnasında ortaya çıkan vasküler yaralanmanın bir sonucu olan kanama nedeniyledir. Aort, trunkus çölyakus ve dallarının birbirleriyle olan yakın komşuluğu nedeniyle mevcut cerrahi prosedürün güvenli bir şekilde devam ettirilmesi için bir manevra gereklidir. Bu manevra ile cerrahi tekniğin standardize edilmesi komplikasyon oranlarını azaltabilir. Bu konuda hala dünyada standartlaşmış ve yerleşik herhangi bir laparoskopik yöntem yoktur. Literatürde var olan tekniklerin birbirlerine üstünlüğünü gösteren herhangi bir randomize kontrollü çalışma yoktur. Bu olgu sunumunda, teknik detayları verilen manevra ile ameliyatın süresi kısalmakta, ayrıca çölyak gövdede mükemmel bir görüntü sağlanmaktadır. Yanısıra, çölyak arter üzerindeki hakimiyeti de kolaylaştırtığından ameliyatı daha da güvenli kılar. Anahtar sözcükler: Çölyak arter kompresyonu; intestinal angina; median arkuat ligament sendromu. Ulus Travma Acil Cerrahi Derg 2020;26(4):642-646

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doi: 10.14744/tjtes.2019.61559

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CA S E R EP O RT

Spontaneous direct inguinal hernia rupture and intestinal mesenteric separation: A case report Özkan Görgülü, M.D.,1

Mehmet Nuri Koşar, M.D.2

Department of Anesthesiology and Reanimation, University of Health Sciences, Antalya Training and Research Hospital, Antalya-Turkey

Department of General Surgery, University of Health Sciences, Antalya Training and Research Hospital, Antalya-Turkey

ABSTRACT Spontaneous evisceration is a rare complication that becomes life-threatening in direct inguinal hernia. A female at the age of 44, weighing 50 kg looked cachectic and was suffering from swelling on the left groin for the last several years.The evisceration of the small intestine as separated from the mesenterium transpired in the subsequent stage of a spontaneous rupture in the left inguinal region after severe coughing. The region ruptured was sealed after small intestine resection carried out through the incision perforated; mesh herniorrhaphy was implemented at the end of the 3rd month. The spontaneous rupture may transpire depending on malnutrition and cachexia not only after the complications by hernia, such as incarceration, strangulation but also after factors increasing intra-abdominal pressure. Elective surgical treatment must be implemented in hernia regardless of its kind. Complications likely to transpire in cases where intervention is conducted too late may threaten the patient’s life. Keywords: Cachexia; malnutrition; mesenteric separation; spontaneous rupture direct inguinal hernia.

INTRODUCTION The spontaneous evisceration is a quite rare case that is lifethreatening.[1] Direct inguinal hernia spontaneously ruptured from the skin and eviscerated small intestine separated from mesenterium are not common complications. Femoral hernia,[2] recurrent inguinal hernia or incisional hernia[3] where the spontaneous rupture is observed in this way are present in the literature. However, the spontaneous rupture of the primary direct inguinal hernia is a case encountered quite rarely. This case study presented the phenomenon of the primary direct inguinal hernia that gets ruptured against the skin in the subsequent stage of severe coughing.

CASE REPORT A female patient, who weighs 50 kg and was 44, looked cachectic applied to the emergency department of Antalya Training and Research Hospital in June 2014, voicing com-

plaints of rupture on the left inguinal region and evisceration of the small intestine. The patient was examined in the emergency care services department; it was found that the patient, who was heavily under the cachectic influence, had been suffering from swelling on the left groin for several years, which was a long period of time, and it was recorded in her medical history that bleeding had occurred as the result of the fact that her intestines protruded since her skin got torn due to severe coughing one hour before the application. The patient and her family were questioned minutely regarding likely trauma and a juridical case; the skin rupture was determined not to be traumatic. HIV and tuberculosis were not detected in tests carried out; there was no drug addiction. There were signs of malnutrition and a well-circumscribed skin opening of 2 cm on the left inguinal region and evisceration of the small intestine segment were observed during the physical examination (Fig. 1a). The patient was immediately operated on; the small intestine segment at the length of 100 cm separated

Cite this article as: Görgülü Ö, Koşar MN. Spontaneous direct inguinal hernia rupture and intestinal mesenteric separation: A case report. Ulus Travma Acil Cerrahi Derg 2020;26:647-649. Address for correspondence: Mehmet Nuri Koşar, M.D. Sağlık Bilimleri Üniversitesi Antalya Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Antalya, Turkey Tel: +90 242 - 249 44 62 E-mail: drkome@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(4):647-649 DOI: 10.14744/tjtes.2020.02435 Submitted: 30.10.2019 Accepted: 12.03.2020 Online: 18.06.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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(a)

(b)

Figure 1. (a) Spontaneous direct inguinal hernia rupture. (b) Small intestine segment separated from the mesenterium.

from the mesenterium was resected through the perforated area of 2 cm without laparotomy implemented; enteroenterostomy was conducted end to end (Fig. 1b). The area of skin open on the left inguinal region was sealed by suture; the patient was nourished orally on the 3rd postoperative day and discharged from hospital on the 5th day in a healthy manner. The patient whose hernial sac was not intervened during the first operation due to infection risk, who did not display any complication in the follow-up period, underwent mesh herniorrhaphy at the end of the 3rd month with the left direct inguinal hernia being planned in advance, whose implementation was optional. No complication was observed during the follow-up period of the patient in the subsequent stage of the second operation.

mesenterium was eviscerated. In our case where there was no previous abdominal operation history, it could be considered that cachexia, malnutrition and the person was too late for treatment might have increased the risk of the spontaneous rupture.

DISCUSSION

Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images.

Inguinal hernia constitutes approximately 75% of all hernia. It is seven times as common in men as in women[4] and 1/3 of inguinal hernia is direct hernia.[5] Not only perforation may progress in direct hernia due to incarceration, strangulation,[6] but also spontaneous rupture may transpire.[2,3] Intraabdominal tuberculosis should absolutely be regarded among the reasons for intestinal perforation since it is common in developing countries in particular.[7] No tuberculosis was detected in this case. In our case, the result of the pathology was the segmentation of small intestine encompassing ischemic alterations. Although the spontaneous rupture is theoretically likely to transpire in each kind of hernia, it has generally been reported in incisional hernia.[7] The spontaneous rupture may transpire in cases that increase intra-abdominal pressure, such as constipation, coughing, straining, lifting heavy objects.[8,9] Although the intestinal segment ruptured is generally affixed to the mesenterium, it is observed in our case that an intestinal segment separated from the 648

Elective surgical treatment must be implemented in hernia regardless of its kind. It must be kept in mind that complications are likely to transpire in cases where intervention is conducted too late may threaten the patient’s life. Here, we have presented a well-managed, although rare, the case where obligation arose to conduct resection to the small intestine segment subjected to the spontaneous rupture, even separated from the mesenterium.

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.N.K.; Design: Ö.G.; Supervision: M.N.K.; Fundings: Ö.G.; Materials: M.N.K.; Data: Ö.G.; Analysis: Ö.G.; Literature search: M.N.K.; Writing: Ö.G.; Critical revision: M.N.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Gupta RK, Sah S, Agrawal SC. Spontaneous rupture of incisional hernia: a rare cause of a life-threatening complication. BMJ Case Rep 2011;2011:bcr1120103486. 2. Kumar A1, Pahwa HS, Pandey A, Kumar S. Spontaneous enterocutaneous fistula due to femoral hernia. BMJ Case Rep 2012;2012:bcr2012006939. 3. West C, Richards J, Sujendran V, Wheeler J. Spontaneous evisceration

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Görgülü et al. Spontaneous direct inguinal hernia rupture and intestinal mesenteric separation of the appendix through an incisional hernia at rest. BMJ Case Rep 2016;2016:bcr2016217585. 4. Chen YH, Wei CH, Wang KK. Children With Inguinal Hernia Repairs: Age and Gender Characteristics. Glob Pediatr Health 2018;5:2333794X18816909. 5. Burcharth J, Andresen K, Pommergaard HC, Bisgaard T, Rosenberg J. Direct inguinal hernias and anterior surgical approach are risk factors for female inguinal hernia recurrences. Langenbecks Arch Surg 2014;399:71–6. 6. Olesen CS, Mortensen LQ, Öberg S, Rosenberg J. Risk of incarceration in

children with inguinal hernia: a systematic review. Hernia 2019;23:245– 54. 7. Zhu LB, Zhang YY, Li JQ, Li PF, Zhang PB, Jin JW. Treatment of an incarcerated inguinal hernia associated with abdominal tuberculosis in an adult patient. J Int Med Res 2018;46:3474–9. 8. Ogundiran TO, Ayantunde AA, Akute OO. Spontaneous rupture of incisional hernia--a case report. West Afr J Med 2001;20:176–8. 9. Martis JJ, Shridhar KM, Rajeshwara KV, Janardhanan D, Jairaj D. Spontaneous rupture of incisional hernia-a case report. Indian J Surg 2011;73:68–70.

OLGU SUNUMU - ÖZET

Spontan rüptüre direkt inguinal herni ve intestinal mezenter ayrışması: Olgu sunumu Dr. Özkan Görgülü,1 Dr. Mehmet Nuri Koşar2 1 2

Sağlık Bilimleri Üniversitesi, Antalya Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, Antalya Sağlık Bilimleri Üniversitesi, Antalya Eğitim ve Araştırma Hastanesi Genel Cerrahi Kliniği, Antalya

Son birkaç yıldır sol kasık bölgesinde şişlik olduğunu bildiren 44 yaşında 50 kg ağırlığında kaşektik görünümlü kadın hasta aynı gün arka arkaya şiddetli öksürük sonrası sol kasığındaki direkt inguinal herni alanında eviserasyon ve mezenter ayrışması olan ince bağırsak evisserasyonu ile acil servise başvurdu. Hastaya evissere olan cilt insizyonundan segmenter ince bağırsak rezeksiyonu ve anastomoz yapıldı. Üç ay sonra fıtık alanı mesh takviye ile onarıldı. İnguinal hernilerde sadece inkarserasyon ve strangülasyon nedeni ile değil kaşeksi ve malnütrisyon durumlarında ani karın içi basınç artışlarında spontan rüptür ve evisserasyon olabileceği akılda tutulmalıdır. Her tür fıtık türünde elektif cerrahi ile tedavi sağlanmalıdır. Aksi halde geciktirilen herni hastalarında gelişebilecek olan komplikasyonların hayatı tehdit edebileceği unutulmamalıdır. Anahtar sözcükler: Kaşeksi; malnütrisyon; mezenterik ayrışma; spontan rüptüre direkt inguinal herni. Ulus Travma Acil Cerrahi Derg 2020;26(4):647-649

doi: 10.14744/tjtes.2020.02435

Ulus Travma Acil Cerrahi Derg, July 2020, Vol. 26, No. 4

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