TJTES 2018-5

ISSN 1306 - 696X

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

Volume 24 | Number 5 | September 2018

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Recep Güloğlu Editors Kaya Sarıbeyoğlu (Managing Editor) M. Mahir Özmen Hakan Yanar Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu 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, Halil Ateş Ortopedics and Traumatology Mahmut Nedim Doral, Mehmet Can Ünlü Plastic and Reconstructive Surgery Ufuk Emekli, Figen Özgür Pediatric Surgery Aydın Yagmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu

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)

Kaya Sarıbeyoğlu M. Mahir Özmen Hakan Yanar Ali Fuat Kaan Gök Osman Şimşek Orhan Alimoğlu Mehmet Eryılmaz

CORRESPONDENCE İLETİŞİM Ulusal Travma ve Acil Cerrahi Derneği Şehremini Mah., Köprülü Mehmet Paşa Sok. Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul, Turkey

Tel: +90 212 - 588 62 46 Fax (Faks): +90 212 - 586 18 04 e-mail (e-posta): travma@travma.org.tr Web: www.travma.org.tr

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)

Kaya Sarıbeyoğlu Kaya Sarıbeyoğlu 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), Index Copernicus, DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, 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 • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): September (Eylül) 2018 • 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.

tion, called “Upload Your Files”.

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 0.473 (JCR 2016). It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PubMed.

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.

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.

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.

Open Access Policy: Full text access is free. There is no charge for publication or 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, 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.

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” sec-

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.

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. 2016 Journal Citation Report IF puanımız 0.473 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.

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 24

Number - Sayı 5 September - Eylül 2018

Contents - İçindekiler Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 379-386 A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats Serbest radikal tutucu Tempol’ün sıçanlarda ven grefti intimal hiperplazisine etkisi Türkmen A, Doğan M, Temel M 387-390 The antibacterial effect of peritoneal fluid in experimental peritonitis Deneysel peritonitte peritoneal sıvının antibakteryel etkisi Ağca B, İşcan AY, Polat E, Memişoğlu K 391-397 Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury Deneysel karaciğer iskemi-reperfüzyon hasarında kalsiyum dobesilatın etkisinin değerlendirilmesi Ünal Y, Küçük B, Tuncal S, Koşmaz K, Çavuşoğlu NT, Kısmet K, Şeneş M, Celepli P, Durak M, Hücümenoğlu S 398-404 Role of pentoxifylline and iloprost in the prevention of ischemia-reperfusion injury in an experimental model of intestine ischemia-reperfusion in rats Sıçanlarda bağırsak iskemi-reperfüzyonunun deneysel modelinde iskemi-reperfüzyon hasarının önlenmesinde pentoksifilin ve iloprostun rolü Abakay U, Soylu S, Göksel S, Saraç B, Şahin İnan ZD, Çakmak E, Korkmaz Ö, Kurt A, Genç HÇ 405-411 Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis Kitosan kaplı ipliklerin anastomoz gücü arttırma üzerine etkisi Altınel Y, Chung SS, Okay G, Uğraş N, Işık AF, Öztürk E, Özgüç H

Original Articles - Orijinal Çalışma 412-416 Efficacy of negative pressure wound therapy in the management of acute burns Akut yanıkların tedavisinde negatif basınçlı yara terapisinin etkinliği Kement M, Başkıran A 417-422 Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery Acil abdominal cerrahi geçiren hastalarda yüzeyel cerrahi alan enfeksiyonu ve ameliyat sonrası ağrıya terapötik hipoterminin etkisi Kılıç E, Uğur M 423-428 Significance of hemogram on diagnosis of acute appendicitis during pregnancy Gebelikte hemogramın akut apandisit tanısındaki önemi Çınar H, Aygün A, Derebey M, Tarım İA, Akalın Ç, Büyükakıncak S, Erzurumlu K 429-433 Role of preoperative C-reactive protein value and neutrophil ratio in the determination of conversion from laparoscopic appendectomy to open appendectomy Ameliyat öncesi C-reaktif protein değeri ve nötrofil yüzdesinin laparoskopik apendektomiden açık apendektomiye konversiyonu belirlemedeki yeri Aydın HO, Avcı T, Tezcaner T, Kırnap M, Yıldırım S, Moray G 434-439 A new and early marker in the diagnosis of acute complicated appendicitis: immature granulocytes Akut komplike apandisit tanısında yeni ve erken bir belirteç: İmmatür granülosit Ünal Y

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

vii

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 24

Number - Sayı 5 September - Eylül 2018

Contents - İçindekiler 440-444 Legal and ethical responsibilities of physicians in coercive situations, such as natural disasters Doğal afetler gibi mücbir durumlarda hekimin hukuki ve etik sorumluluğu

Şenel Eraslan B, Karadayı B, Çakı İE, Aslan N, Varlık Tokgözoğlu E, Kılıç Ç, Özaslan A, Çetin G 445-449 Mortality determiners for fall from height cases Yüksekten düşme olgularında mortaliteye neden olan faktörler

Akkoca M, Tokgöz S, Yılmaz KB, Güler S, Akıncı M, Balas Ş, Karabacak H, Saydam M 405-455 Retrospective analyses of high-energy explosive device-related injuries of the ear and auricular region: experiences in an operative field hospital emergency room Kulak ve aurikular bölgenin yüksek enerjili patlayıcılar kaynaklı yaralanmalarının geriye dönük analizi: Operasyon saha hastanesi acil servis deneyimleri Aşık MB, Binar M 456-461 Clinical evaluation of negative-pressure wound therapy in the management of electrical burns Negatif başınçlı yara tedavisinin elektrik yanıklarında klinik olarak değerlendirilmesi Eyvaz K, Kement M, Balin S, Acar H, Kündeş F, Karaoz A, Civil O, Eser M, Kaptanoglu L, Vural S, M, Bildik N 462-467 Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations

Parmak ucu amputasyonlarında repoziyon flebi kullanımı ve replantasyonların uzun dönem sonuçlarının karşılaştırılması

Sir E, Aksoy A, Kasapoğlu Aksoy M 468-473 Does computerized tomography help to shorten the immobilization period in the plaster treatment of nondisplaced scaphoid fractures?

Nondeplase skafoid kırıkların alçı tedavisinde bilgisayarlı tomografi immobilizasyon süresini kısaltmaya yardımcı olur mu? Çümen H, Duramaz A, Kural C 474-480 Utility of the Three-Point Index in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures Çocuk önkol orta 1/3 kırıklarının konservatif tedavisi sırasında redüksiyon kaybının saptanmasında “Three Point Index”in kullanılabilirliği Taşdemir Z, Bulut G, Çevik B, Eceviz E, Günay H 481-487 Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats Sıçanlarda deneysel olarak oluşturulan siyatik sinir hasarında gabapentinin primer cerrahi tedaviye etkisi Kardeş Ö, Çivi S, Bulduk EB, Kaya Selçuk F, Süner Hİ, Durdağ E, Tufan K 488-496 Risk factors for morbidity in walled-off pancreatic necrosis and performance of continuous postoperative lavage: A single-center experience

Walled-off pankreatik nekrozda morbiditiye etki eden risk faktörleri ve ameliyat sonrası sürekli lavajın etkinliği: Tek merkez deneyimi Aziret M, Ercan M, Toka B, Parlak E, Karaman K

Case Report - Olgu Sunumu

497-500 Heparin-free veno-venous ECMO applied to a patient with severe lung contusion and hypovolemic shock due to trauma Travmaya bağlı ciddi akciğer kontüzyonu ve hipovolemik şoku olan bir hastaya heparin verilmeden uygulanan veno-venöz ECMO

Moon SH, Kim KN, Jung JJ, Park JH, Byun JH viii

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

EXPERIMENTAL STUDY

A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats Arif Türkmen, M.D.,1

Mehmet Doğan, M.D.,2

Metin Temel, M.D.3

1

Department of Plastic, Reconstructive and Aeshetic Surgery, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

2

Department of Plastic, Reconstructive and Aesthetic Surgery, Private Office Physician, Gazi̇ antep-Turkey

3

Department of Plastic, Reconstructive end Aesthetic Surgery, Private Antakya Yaşam Surgical Medical Center, Hatay-Turkey

ABSTRACT BACKGROUND: Reversed vein grafting exposes the vessel to a period of ischemia, reperfusion and subsequent reactive oxygen species, which may damage endothelial tissue, smooth muscle cell proliferation and later the development of intimal hyperplasia.

Tempol is a free radical scavenger that permeates biological membranes. This study investigates the effects of a free radical scavenger (Tempol) on intimal hyperplasia of femoral vein grafts and the level of reactive oxygen species in rats.

METHODS: Arterial defects created in the femoral artery of rats were repaired with ipsilateral femoral vein grafts. Tempol was administered to group T and saline to group C on a daily basis for a period of 28 days. Blood samples were measured.

RESULTS: The veins were stained with H&E and Verhoeff’s elastic stains. Binary comparison revealed a statistically significant difference for intimal and medial thicknesses (p<0.01).

CONCLUSION: This study found that a free radical scavenger (Tempol) prevents the early development of intimal hyperplasia, most probably by inhibiting the infiltration of polymorph nuclear monocytes (PNM), with evidence of increased levels of antioxidant products and decreased levels of free oxygen radicals.

Keywords: Intimal hyperplasia; microsurgery; reactive oxygen species; Tempol; vein graft.

INTRODUCTION Autogenous vein graft remains one of the most commonly used graft materials for the treatment of occlusive vascular disease or closing defects in the artery.[1–3] However, these grafts are prone to failure due to thrombosis, which occurs in as many as 20% of cases within the first week after surgery.

Intermediate graft failure (from 30 days to 2 years after surgery) and late graft failure (≥2 years after surgery) occurs in 20%–50% cases within five years after surgery.[1,4] The main cause of intermediate and late vein graft failure following surgery is intimal and medial hyperplasia.[5] Although the etiology of the intimal hyperplasia of the vein graft is not exactly known, many factors, such as graft manipulation, compliance with mismatch of artery, and vein graft,

increase wall shear stresses and reperfusion can be responsible for triggering the mechanism of intimal hyperplasia.

Endothelium also plays a pivotal role in the development of intimal hyperplasia.[6–8] Reactive oxygen species (ROS), which are superoxide anions, hydroxyl radicals, hydrogen peroxide (H2O2), and peroxynitrite are produced in metabolic and physiological processes.

They may damage cells by causing peroxidation of membrane lipids, denaturation of proteins, including enzymes and ion channels, and strand breaks in DNA. However, ROS have also recently been shown to stimulate vascular smooth muscle cell growth and proto oncogen expression that cause intimal hyperplasia.[9] Superoxide regulates redox-sensitive signaling pathways and acts as a direct vascular smooth muscle cell mitogen.[10] It also modulates vessel remodeling by activating

Cite this article as: Türkmen A, Doğan M, Temel M. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats.

Ulus Travma Acil Cerrahi Derg 2018;24:379-386.

Address for correspondence: Arif Türkmen, M.D. İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Plastik Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 414 30 00 E-mail: turkmenarif@yahoo.com Ulus Travma Acil Cerrahi Derg 2018;24(5):379-386 DOI: 10.5505/tjtes.2017.80281 Submitted: 10.09.2017 Accepted: 22.11.2017 Online: 20.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

379

Türkmen et al. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats

matrix metalloproteinase[8,11] and influences vascular smooth muscle cell migration and apoptosis.[10,12] ROS can be removed by enzymatic or non-enzymatic antioxidative mechanisms in organisms, and their harmful reactions can be prevented or inhibited by antioxidant molecules.

Paraoxonase (PON1) is an ester hydrolase, which has both arylesterase and paraoxonase activities. Recently, PON1 has been studied for its antiatherogenic and antioxidant effects in a number of processes, including lipid and lipoprotein metabolism. Oxidative stress, which is the result of an increased number of lipid and protein oxidation products and a decreased number of antioxidant enzymes and vitamins, has been reportedly affects the expression and activities of PON1. Furthermore, oxidative stress has been shown to decrease PON1 activity and to down-regulate the serum expression of PON1.[13] Tempol (4-hydroxy-2,2,6,6-tetramethyl-4-piperidinyloxyle) is a superoxide dismutase-mimetic compound, chemically stable, cell-permeable, and non-toxic, that has been shown to possess powerful anti-superoxide activity and prevent the formation of hazardous peroxyl radicals.[9,10,12,14] There are high levels of evidence from preclinical studies that Tempol reduces the degree of local and systemic inflammation and associated tissue injury. It has been used for the treatment of pancreatitis, pleurisy, arthritis, colitis, and uveoretinitis.[15] The aim of this study was to investigate the effect of Tempol, which is a membrane-permeable, free radical scavenger, on the intimal hyperplasia of the vein graft for surgically created femoral artery defects in rats and its correlation with the level of the total antioxidant capacity (TAC), total oxidant status (TOS), and Paraoxanase-1 (Pon) level in blood.

MATERIALS AND METHODS

an end to-end manner using interrupted 10/0 nylon suture (Ethilon; Ethicon Inc.) under magnification (Fig. 1). The ischemia times of the veins were 43–49 min. The wounds were closed primarily.

The rats were randomized into two groups. The first group was the control (Group C, n=10) and the other was Tempol (Group T, n=10). Tempol granules were dissolved in sterile saline 10 mg/cc and then injected (30 mg/kg/day) intraperitoneally to Group T, while 0.8 cc saline was injected to Group C daily to obtain same stress conditions during the 28 days.

Blood samples from the rats were obtained just before sacrifice to measure TAC, total oxidation status, and Proxanase–1 levels. All animals were sacrificed using sodium pentobarbital (100 mg/kg i.v) (Penthotal Sodium, Abbott Laboratuvarı A.Ş.).

A catheter was inserted into the aorta and isotonic saline solution was infused until clear fluid was seen passing through the right femoral vein graft. The vein graft was removed including 5 mm of the distal and proximal parts of the anastomoses and was fixed in a buffered formaldehyde solution (10% phosphate-buffered saline, PBS) at room temperature.

Histological and Morphometric Studies Cross-sections from the proximal third, middle third, and distal third of each vein graft were taken. Four-μm thick sections were cut from the middle of these segments, and six coated glass slides were prepared from each vein sample, stained with Verhoeff’s elastic tissue stain and H&E. The intimal and medial layers were identified by a demarcation between the criss-cross orientation of the intimal hyperplasic smooth muscle cells and circular smooth muscle cells of the media. The outer limit of media was defined by the interface between the circular smooth muscle cells of the media and the connective tissue of the adventitia. The specimens were examined using a Nikon Eclips E600 microscope and imaged

The study included 20 healthy adult, male Wistar Albino rats who were 105–120 days old and weighed 250–300 g. Subjects were randomly divided into two groups of ten subjects. Their care complied with the Principle of Laboratory Animal Care and the Guide for Care and Use of Laboratory Animals’ (NIH Publication No. 80–23, revised 1985).

The rats were anesthetized with an intra peritoneal (ip) injection of ketamine (50 mg/kg) (Ketalar, Eczacıbaşı, Turkey), followed by another injection of xylazine (10 mg/kg), (Rompun, Bayer, Turkey) into the subcutaneous tissue of the right groin. The right femoral artery and vein were exposed. There was no obvious discrepancy between the femoral artery and vein diameters. A 2-cm femoral artery was removed, and the gap between arteries was then measured. A femoral vein graft was harvested from the right femoral vein, as needed, at the same time. The femoral vein graft was washed with a heparin–saline solution (5 IU/ml), and the arterial defect was repaired with the reversed interposition femoral vein graft in 380

Figure 1. The reversed interpositional femoral vein graft in the arterial defect.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Türkmen et al. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats

Figure 2. The light microscopic appearance of the intimal hyperplasia of the vein grafts.

with a Nikon Digital Sight DS-L1 photomicroscope (Fig. 2).

A ratio of the intimal and medial areas was also calculated.

The images were analyzed with a computer Analysis System Program.

hanced by glycerol molecules, which are abundantly present in the reaction medium. The assay is calibrated with hydrogen peroxide, and the results are expressed in terms of µm hydrogen peroxide equivalent/L.

Biochemical Analysis Measurement of Total Antioxidant Capacity (TAC)

Oxidative Stress Index (OSI)

Plasma TAC levels were determined using a novel automated measurement method developed by Erel.[16] In this method, hydroxyl radical, which is the most potent radical, was produced via Fenton reaction. In this assay, the antioxidative effect of the sample against the potent free radical reactions (initiated by the produced hydroxyl radical) was measured.

The results are expressed as mmol Trolox equivalent/L.

Measurement of Total Oxidant Status (TOS) Plasma TOS levels were determined using a novel automated measurement method developed by Erel.[17] In this method, oxidants present in the sample oxidize the ferrous ion–o-dianisidine complex to ferric ion. The oxidation reaction is en-

Group T

The percent ratio of TOS to TAS gave the oxidative stress index (OSI), which is an indicator of the degree of oxidative stress.[16,17] To perform the calculation, the result unit of TAS (mmol Trolox equivalent/L) was converted to mol equivalent/l and the OSI value was calculated as follows; OSI = [(TOS, mol/l) / (TAS, mmol Trolox equivalent/ l) × 100].

Measurement of Paraoxonase-1 Level The basal activity of paraoxonase was measured using paraoxon. The rate of paraoxon hydrolysis (diethyl-p-nitrophenylphosphate) was measured by monitoring an increase in absorbance at 412 nm at 37ºC on an autoanalyzer (Beckman Coulter, Fullerton, CA, and U.S). Paraoxonase activity was expressed as U/L of serum.[13]

Group C

Figure 3. Scar tissue surrounding the graft at macroscopic appearance.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

381

Türkmen et al. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats

excluded from the study and substituted with a new one. No complications were encountered during the experiment.

Histological Findings There was a good blood flow within the vein grafts in both the groups. However, there was more scar tissue surrounding the vein grafts in the control group at observation, and dissection of the vein graft was more difficult (Fig. 3). The light microscopic appearance of the vein grafts in Group C demonstrated a profound degree of intimal and medial hyperplasia with the proliferation of smooth muscle cells and the infiltration of polymorph nuclear cells. The adventitial collagenous tissue had also increased (Figs. 4, 5).

Group C x100

Figure 4. Intimal and media hyperplasia with proliferation of smooth muscle cells, and infiltration of polymorph nuclear cells.

Statistical Analysis Statistical analysis was performed using SPSS (The Statistical Package for Social Sciences) software for Windows, release 14.0. Results are expressed as the mean±standard deviation (SD). Statistical analysis was performed using the Mann– Whitney U test and Paired t-test. Statistical significance was assumed at a level of p<0.01.

RESULTS The study was completed 28 days following the surgery. In the post-operative follow-up period, infection was observed in only one subject of Group C and that study subject was

Group C

The thickness of the intimal and medial layers of the vein graft as well as the ratio of the intima to media in Groups C and T, respectively, are shown in Table 1. There were statistically significant differences in the ratio of the intimal and medial layer thickness of the vein grafts between the two Groups (p<0.01). However, there were no statistically significant differences between the ratio of the intima and media of the two groups (p≥0.01) (Table 1).

Biochemical Findings Mean and SD values of TAC, TOS, OSI, and PON-1 levels are presented in Table 2. The results of TAC and PON-1 were significantly higher in Group T than in Group C (p<0.01).

However, the result of TOS and OSI were significantly lower in Group T than in Group C (p<0.01) (Figs. 6–8).

DISCUSSION The major findings of this study are that Tempol increases the level of TAC and PON-1, which are antioxidant products, at a significant level (p<0.01) and decreases the level of TOS and OSI, also at a statistically significant level. Furthermore,

Group T

Figure 5. Compression of the vessel layers stained with Verhoeff’s elastic tissue stain.

382

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Türkmen et al. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats

Table 1. The mean thickness of intimal and medial layers of the vessel and the mean ratio of the intima to media Groups

The thickness of the intima (µm)

The thickness of the media (µm)

Intima/Media ratio

Group 1 (Group C)

15.530±3.438

21.830±3.176

0.706±0.095

Group 2 (Group T)

8.540±0.544

13.300±0.997

0.646±0.073

Table 2. The comparison of the level of total antioxidant capacity (TAC), total oxidation level (TOS), Proxanase–1(PON-1), and oxidative stress index (OSI) Groups

TAC

TOS

OSI

PON-1

Group 1 (Group C)

1.231±0.188

7.482±2.008

0.625±0.217

85.645±36.482

Group 2 (Group T)

1.590±0.115

2.443±1.096

0.154±0.072

281.298±16.770

TAC: Total Antioxidant Capacity µmol Trolox Eqv./L; TOS: Total Oxidation Level µmol H2O2 Eqv./L; OSI: oxydative stress index TOS/TAS; PON-1: Proxanase–1; HDLAssociated enzyme.

The first interposition vein graft for arterial defect was used in the beginning of the nineteenth century. Intimal hyperplasia was also first described at that time.[18] Vein grafts undergo structural changes following insertion in to the arterial circulation with the development of intimal hyperplasia.[19] The internal pressure of the vein is up to 10 mmHg. Following vein graft repair, the vein is immediately subjected to an arterial pressure of 100 mmHg as well as an immediate increase in flow, longitudinal wall (shear) stress, circumferential stress, radial deformation, radial stress, pulsatile deformation, and pulsatile stress.[20] Hemodynamic forces have been postulated as promoters of intimal hyperplasia.[21] These are all associated with an increased expression of growth factors, adhesion molecule expression, and proliferation. Intimal hyperpla-

sia is a universal response of a vein graft repair to an artery that results from both the migration of smooth muscle cells out of the media into the intima and proliferation of these smooth muscle cells.[22] Later, smooth muscle cells deposit a complex extracellular matrix.[23] In general, intimal hyperplasia is a self-limiting process, which does not produce luminal compromise, and usually becomes quiescent within 2 years of graft insertion. However, in fo350

Level of the PON1 in Group T and Group C

300 The level of PON1

the thickness of both intimal and medial layers of the vein was significantly thinner in Group T than Group C (p<0.01). Not surprisingly, there was no statistical difference in the intima to media ratio between Group T and Group C (p≥0.01) because both intimal and medial layers increased in the control group and decreased in Tempol group; therefore, this ratio was constant.

250 200 150 100 50 0

Group T

Groups

Group C

Figure 7. Paraoxonase-1 levels.

Comparison of TAC and TOS Level

9 8

0.8

7 6

0.7

5

0.6

4

0.5

3

0.4

2

0.3

1 0

The level oxydative stress index (OSI)

0.2 TAV level Group T

TAV level Group C

TOS level Group T

TOS level Group C

Figure 6. Comparison of the total antioxidant capacity (TAC) and total oxidant status (TOS).

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

0.1 0

Group T

Group C

Figure 8. The oxidative stress index.

383

Türkmen et al. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats

cal areas, the intimal hyperplasia can proceed to significant stenosis.[24–26] Many agents, which successfully reduce the formation of intimal hyperplasia in experimental vein grafts, can also affect the smooth muscle cell physiological phenotypes identified by alterations in vein graft vasomotor contractile function.[14,24,27] The process that leads to intimal hyperplasia and changes in endothelial and smooth muscle cell physiology begins early after grafting into the arterial circulation.[19] Recent studies suggest that the infiltration of PMNs and oxygen free radical injury are associated with the early development of intimal hyperplasia.[25,28,29] Previous studies have shown that chronic in vivo administration of either aspirin with dipyridamole, heparin, verapamile, or captopril reduces the development of intimal hyperplasia in vein bypass graft.[22,30–37] Harvesting a vein has a period of ischemia due to loss of continuity of the vasa vasorum. A study showed that a pig saphenous vein becomes rapidly hypoxic after excision and remains so after implantation for at least a month. As the vein graft thickens rapidly, the graft is likely subject to an increase in oxygen demand, which may also increase hypoxia.[38] Hypoxia of the vein graft promotes superoxide anion (O2−) formation via activation of nicotinamide adenine dinucleotide phosphate oxidize, xanthine oxidise, and mitochondrial respiratory chain. Prolonged hypoxia regulates the expression of many proteins that can cause cell injury and are responsible for the vein graft failure,[30,39,40] Another study showed that H2O2 induced DNA synthesis and proto oncogen c-myc, which encodes a transcription factor that regulates cell proliferation, growth, and apoptosis and c-fos mRNA expression in vascular smooth muscle.

The administration of exogenous superoxide dismutase (SOD) is known to inhibit the injuries caused by oxygenderived free radicals. However, it has an extremely short life span (6 min) and large molecular weight (30000 kd), making it unable to cross the cell membrane. This prevents its intracellular availability where free radicals are generated.[41–43] Tempol permeates biological membranes and accumulates in the cytosol. It is capable of scavenging superoxide and hydroxyl radicals at the membrane as well as both intracellular and extracellular. Although it’s precise mechanism of action is still not clearly understood, many studies showed that Tempol attenuates the effects of superoxide anions. Not only does Tempol reduce the formation of hydroxyl radicals but it also prevents the injury/death caused by H2O2 in rat cardiac myoblasts by preventing the effects of hydroxyl radicals. ROS and peroxynitrite can cause DNA strand breaks, and this effect is abolished by Tempol.[15] Systemic administration of Tempol causes a systemic vasodilatation and decreases the heart rate. These effects may be due to the formation of metabolite hydroxylamine and the enhanced bioavailability of nitric oxide (NO).[42] Vasodilatator effect of Tempol may also reduce the development of the intimal hyperplasia of the graft.

384

Tempol increases NO availability by inhibiting its destruction and other superoxide-derived ROS[12,31] and prevents the formation of hazardous peroxyl radicals. It protects against oxidant stress-induced endothelial dysfunction.[42] Our study showed that Tempol reduced scar formation around the vein graft, as well as the local inflammatory response within the intimal and medial layers of the vein graft.

Other free radical scavengers, such as vitamin E and lazaroid, have been used to reduce intimal hyperplasia of the vein graft.

However, in contrast to the effect of Tempol, they scavenge hydroxyl radicals only in the membrane.[19,44] Moreover, there is very limited evidence that long-term exposure of cells to Tempol may cause cell injury.

Conclusion We have established a link between ROS and intimal hyperplasia of the vein graft. Treatment with Tempol, which is a free radical scavenger, can decrease the early development of intimal hyperplasia, possibly by inhibiting the infiltration of PNM with evidence of increasing the level of antioxidant products and decreasing the level of free oxygen radicals, which are mediated injury to the endothelium of the vein grafts.

Acknowledgments None of the authors have a financial interest in any of the products, devices, or drugs mentioned in this article.

Funding This project was supported by Gaziantep University of Medical Sciences.

Conflict of interest: None declared.

REFERENCES 1. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 2000;31:S1–296.

2. Kapadia MR, Popowich DA, Kibbe MR. Modified prosthetic vascular conduits. Circulation 2008;117:1873–82.

3. Vijayan V, Smith FC, Angelini GD, Bulbulia RA, Jeremy JY. External supports and the prevention of neointima formation in vein grafts. Eur J Vasc Endovasc Surg 2002;24:13–22.

4. Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and Circulation 1998;97:916–31.

5. Schwartz SM, deBlois D, O’Brien ER. The intima. Soil for atherosclerosis and restenosis. Circ Res 1995;77:445–65.

6. Allaire E, Clowes AW. Endothelial cell injury in cardiovascular surgery: the intimal hyperplastic response. Ann Thorac Surg 1997;63:582–91.

7. Bergan JJ, Veith FJ, Bernhard VM, Yao JS, Flinn WR, Gupta SK, et al.

Randomization of autogenous vein and polytetrafluorethylene grafts in femoral-distal reconstruction. Surgery 1982;92:921–30.

8. Johnson F, Giulivi C. Superoxide dismutases and their impact upon human health. Mol Aspects Med 2005;26:340–52.

9. Onuma S, Nakanishi K. Superoxide dismustase mimetic tempol decreases blood pressure by increasing renal medullary blood flow in hyper-

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Türkmen et al. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats insulinemic-hypertensive rats. Metabolism 2004;53:1305–8.

10. Nigri GR, Kossodo S, Waterman P, Fungaloi P, LaMuraglia GM. Free radical attenuation prevents thrombosis and enables photochemical inhibition of vein graft intimal hyperplasia. J Vasc Surg 2004;39:843–9.

11. Mahler F, Baumgartner I, Do DD. Stenting of the peripheral, renal and supraaortic arteries and the aorta. Schweiz Med Wochenschr 1999;129:399–409.

12. Guo R, Gao XY, Wang W, Wang HJ, Zhang F, Zhang Y, et al.Tempol reduces reperfusion-induced arrhythmias in anaesthetized rats. Pharmacol Res 2005;52:192–8.

13. Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, et al.Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999;26:892–904.

14. Hamilton CA, Berg G, Mcintyre M, Mcphaden AR, Reid JL, Dominiczak AF. Effects of nitric oxide and superoxide on relaxation in human artery and vein. Atherosclerosis 1997;133:77–86.

15. Thiemermann C. Membrane-permeable radical scavengers (tempol) for shock, ischemia-reperfusion injury, and inflammation. Crit Care Med 2003;31:S76–84.

16. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–11.

17. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation.

Clin Biochem 2004;37:277–85.

18. Carrel A. Landmark article, Nov 14, 1908: Results of the transplantation of blood vessels, organs and limbs. By Alexis Carrel. JAMA 1983;250:944–53.

19. Davies MG, Dalen H, Barber L, Svendsen E, Hagen PO. Lazaroid therapy (methylaminochroman: U83836E) reduces vein graft intimal hyperplasia. J Surg Res 1996;63:128–36.

20. Dobrin PB, Littooy FN, Endean ED. Mechanical factors predisposing to intimal hyperplasia and medial thickening in autogenous vein grafts.

Surgery 1989;105:393–400.

21. Cunnane CV, Cunnane EM, Walsh MT. A Review of the Hemodynamic Factors Believed to Contribute to Vascular Access Dysfunction. Cardiovasc Eng Technol 2017;8:280–94.

22. Davies MG, Hagen PO. Pathobiology of intimal hyperplasia. Br J Surg 1994;81:1254–69.

23. Simic DV, Mimic-Oka J, Pljesa-Ercegovac M, Savic-Radojevic A, Opacic M, Matic D, et al. Byproducts of oxidative protein damage and antioxidant enzyme activities in plasma of patients with different degrees of essential hypertension. J Hum Hypertens 2006;20:149–55.

24. Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK. Free radicals and the heart. J Pharmacol Toxicol Methods 1993;30:55–67.

25. Rosenfeldt FL, He GW, Buxton BF, Angus JA. Pharmacology of coronary artery bypass grafts. Ann Thorac Surg 1999;67:878–88.

26. Zubilewicz T, Wronski J, Bourriez A, Terlecki P, Guinault AM, Muscatelli-Groux B, et al. Injury in vascular surgery-the intimal hyperplastic response. Med Sci Monit 2001;7:316–24.

27. Koniari I, Mavrilas D, Apostolakis E, Papadimitriou E, Papadaki H, Papalois A, et al. Inhibition of Atherosclerosis Progression, Intimal Hyperplasia, and Oxidative Stress by Simvastatin and Ivabradine May Reduce Thoracic Aorta’s Stiffness in Hypercholesterolemic Rabbits. J Cardiovasc

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Pharmacol Ther 2016;21:412–22.

28. Brahmbhatt A, Misra S. The Biology of Hemodialysis Vascular Access Failure. Semin Intervent Radiol 2016;33:15–20 29. Bonder CS, Knight D, Hernandez-Saavedra D, McCord JM, Kubes P. Chimeric SOD2/3 inhibits at the endothelial-neutrophil interface to limit vascular dysfunction in ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol 2004;287:G676–84.

30. Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ. Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 1995;121:1845–54.

31. Fulton GJ, Davies MG, Barber L, Svendsen E, Hagen PO. Localized versus systemic angiotensin II receptor inhibition of intimal hyperplasia in experimental vein grafts by the specific angiotensin II receptor inhibitor L158,809. Surgery 1998;123:218–27.

32. Mehta JL, Nichols WW, Donnelly WH, Lawson DL, Thompson L, ter Riet M, et al. Protection by superoxide dismutase from myocardial dysfunction and attenuation of vasodilator reserve after coronary occlusion and reperfusion in dog. Circ Res 1989;65:1283–95.

33. West N, Guzik T, Black E, Channon K. Enhanced superoxide production in experimental venous bypass graft intimal hyperplasia: role of NAD(P) H oxidase. Arterioscler Thromb Vasc Biol 2001;21:189–94.

34. O’Donohoe, M.K., et al., Chronic ACE inhibition reduces intimal hyperplasia in experimental vein grafts. Ann Surg 1991;214:727–32.

35. Roux SP, Clozel JP, Kuhn H. Cilazapril inhibits wall thickening of vein bypass graft in the rat. Hypertension 1991;18:II43–6.

36. Varty K, Allen KE, Jones L, Sayers RD, Bell PR, London NJ. Influence of Losartan, an angiotensin receptor antagonist, on neointimal proliferation in cultured human saphenous vein. Br J Surg 1994;81:819–22.

37. Volk T, Hensel M, Schuster H, Kox WJ. Secretion of MCP-1 and IL-6 by cytokine stimulated production of reactive oxygen species in endothelial cells. Mol Cell Biochem 2000;206:105–12.

38. Jeremy JY, Gadsdon P, Shukla N, Vijayan V, Wyatt M, Newby AC, et al. On the biology of saphenous vein grafts fitted with external synthetic sheaths and stents. Biomaterials 2007;28:895–908.

39. Joddar B, Firstenberg MS, Reen RK, Varadharaj S, Khan M, Childers RC, et al. Arterial levels of oxygen stimulate intimal hyperplasia in human saphenous veins via a ROS-dependent mechanism. PLoS One 2015;10:e0120301.

40. Khattab MM. TEMPOL, a membrane-permeable radical scavenger, attenuates peroxynitrite- and superoxide anion-enhanced carrageenan-induced paw edema and hyperalgesia: a key role for superoxide anion. Eur J Pharmacol 2006;548:167–73.

41. Laight DW, Andrews TJ, Haj-Yehia AI, Carrier MJ, Anggård EE. Microassay of superoxide anion scavenging activity in vitro. Environ Toxicol Pharmacol 1997;3:65–8.

42. McDonald MC, Zacharowski K, Bowes J, Cuzzocrea S, Thiemermann C. Tempol reduces infarct size in rodent models of regional myocardial ischemia and reperfusion. Free Radic Biol Med 1999;27:493–503.

43. Mitchell JB, Samuni A, Krishna MC, DeGraff WG, Ahn MS, Samuni U, et al. Biologically active metal-independent superoxide dismutase mimics.

Biochemistry 1990;29:2802–7.

44. Hagen PO, Davies MG, Schuman RW, Murray JJ. Reduction of vein graft intimal hyperplasia by ex vivo treatment with desferrioxamine manganese. J Vasc Res 1992;29:405–9.

385

Türkmen et al. A free radical scavenger (Tempol) and its effect on intimal hyperplasia of vein grafts in rats

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Serbest radikal tutucu Tempol’ün sıçanlarda ven grefti intimal hiperplazisine etkisi Dr. Arif Türkmen,1 Dr. Mehmet Doğan,2 Dr. Metin Temel3 1 2 3

İstanbul Üni̇ versi̇ tesi̇ Cerrahpaşa Tıp Fakültesi̇ , Plasti̇ k, Rekonstrükti̇ f ve Estetik Cerrahi̇ Anabilim Dalı, İstanbul Serbest Muayenehane Heki̇ mi̇ , Plastik, Rekonstrüktif ve Estetik Cerrahi Uzmanı, Gazi̇ antep Özel Antakya Yaşam Cerrahi̇ Tıp Merkezi̇ , Plasti̇ k, Rekonstrükti̇ f ve Esteti̇ k Cerrahi̇ Klini̇ ği̇ , Hatay

AMAÇ: Vasküler defektlerin onarımı sonrasında kullanılan ven greftinin iskemi ve reperfüzyon hasarı sonrası reaktif oksijen radikalleri oluşarak endotelyal dokuya, vasküler düz kaslara etki ederek intimal hiperplaziye neden olmaktadır. Tempol serbest radikalleri tutarak biyolojik memeranlarda stabilizasyon sağlamaktadır. Bu çalışmada femoral arter defektlerinin ven grefti ile onarıldığı sıçanlarda Tempol’ün intimal hiperplazi ve serbest oksijen radikallerinin düzeyleri değerlendirildi.

GEREÇ VE YÖNTEM: Sıçanların femoral arterlerinde bir defekt oluşturularak oluşan defekt aynı taraftan ven grefti alınarak onarıldı. Sıçanlar iki gruba ayrıldı. Yirmi sekiz gün boyunca hergün intraperitoneal olarak Tempol verilenler grup T ve serum fizyolojik verilenler grup C olarak adlandırıldı.

Deney sonunda kan ve vasküler doku örnekleri alındı.

BULGULAR: Ven greftleri hematoksilen-eozin ve Verhoeff ’in elastin boyası ile değerlendirildi. Gruplar intimal hiperplazi ve media tabakasındaki kalınlıkları bakımından karşılaştırıldığında istatistiksel olarak belirgin fark olduğu tespit edildi (p<0.01).

TARTIŞMA: Bu çalışmada serbest radikal tutucu Tempol’ün erken dönemde gelişen intimal hiperplaziyi engellediği gösterildi. Tempol’ün bu etkiyi media tabakası ve ven endoteline zararlı serbest oksijen radikallerinin düzeyini azaltarak ve anti-oksidan ürünlerin seviyesini arttırarak ve muhtemelen bu etkiler sonucu polimorf nükleer lökositlerin infiltrasyonunu engelleyerek gerçekleştirdiği düşünülmektedir.

Anahtar sözcükler: Intimal hiperplazi; mikrocerrahi; reaktif oksijen türevleri; Tempol; ven grefti.

Ulus Travma Acil Cerrahi Derg 2018;24(5):379-386

386

doi: 10.5505/tjtes.2017.80281

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

EXPERIMENTAL STUDY

The antibacterial effect of peritoneal fluid in experimental peritonitis Birol Ağca, M.D.,1

Ahmet Yalın İşcan, M.D.,1

Erdal Polat, M.D.,2

Kemal Memişoğlu, M.D.1

Department of General Surgery, University of Health Sciences, İstanbul Fatih Sultan Mehmet Training and Research Hospital, İstanbul-Turkey

1 2

Department of Microbiology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: In our study, the effects of peritoneal fluid on some Gram-negative and Candida albicans in experimental peritonitis rats were studied. The primary objective of the present study was to understand the effect of peritoneal fluid on microorganisms causing intra-abdominal infections.

METHODS: Twenty male Sprague–Dawley rats weighing between 250 and 300 g were used in the study. The rats were randomly divided into two groups consisting of 10 animals. The operative procedures were performed under sterile conditions. In group I, sham laparotomy was done. In group II, the distal part of the cecum was ligated, and cecum perforation was performed. Peritoneal fluid samples at baseline and 2 and 4 h were extracted using a Pasteur pipette during laparotomy under anesthesia.

RESULTS: Peritoneal fluid was ineffective on Citrobacter freundii, Proteus mirabilis, and Enterobacter aerogenes. It inhibited the growth of Klebsiella pneumoniae for 8 h. However, growth was significantly increased in the passages obtained after 24 h. The growth of C. albicans decreased in the passages that were extracted after 4 and 8 h and increased in the passages obtained after 24 h (p<0.05).

It was found that the number of Escherichia coli and Pseudomonas aeruginosa colonies that were grown in 2 h decreased, and no growth was detected in the passages obtained after 2 h (p<0.05).

CONCLUSION: Proliferating colony counts of E. coli and P. aeruginosa decreased after 2 h, and there was no proliferation in subsequent cultures. Peritoneal fluid exhibits a bactericidal effect under appropriate conditions. It also exhibits peritoneal bactericidal activity against E. coli, the major pathogen in intra-abdominal infections.

Keywords: Gram-negative bacteria; peritoneal defense; peritoneal fluid effects.

INTRODUCTION The peritoneum is the largest serous membrane of the human body. It is a continuous transparent membrane that lines the abdominal cavity and covers the abdominal organs. It consists of two layers that are continuous with each other, the parietal peritoneum and the visceral peritoneum. They are both composed of a layer of simple squamous epithelial cells called mesothelium. The parietal peritoneum lines the internal surface of the abdominopelvic wall. The visceral peritoneum invaginates to cover the majority of the abdominal viscera. It is derived from the somatic mesoderm in the embryo. The visceral and parietal peritoneum have similar

structural compositions consisting of three distinctive layers: mesothelium, basal lamina, and submesothelial stroma.

The mesothelial membrane that lines the abdominal cavity is situated directly beneath the abdominal musculature and comprises a thin layer of loose connective tissue covered by a single layer of mesothelial cells.[1] These membranes function to prevent friction between closely packed organs by secreting serum that acts as a lubricant, to help hold the abdominal organs in their proper positions, to separate and unite organs, and to act as a barrier against infection. The peritoneal cavity is a potential space between the parietal and visceral peritoneum. It contains a small

Cite this article as: Ağca B, İşcan AY, Polat E, Memişoğlu K. The antibacterial effect of peritoneal fluid in experimental peritonitis. Ulus Travma Acil Cerrahi Derg 2018;24:387-390.

Address for correspondence: Birol Ağca, M.D. Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, E5 Bostancı Mevki, Ataşehir, 34758 İstanbul, Turkey Tel: +90 216 - 578 30 00 E-mail: birolagca@yahoo.com Ulus Travma Acil Cerrahi Derg 2018;24(5):387-390 DOI: 10.5505/tjtes.2018.10452 Submitted: 16.02.2018 Accepted: 16.07.2018 Online: 16.07.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

387

Ağca et al. The antibacterial effect of peritoneal fluid in experimental peritonitis

amount of lubricating fluid. It also contains only a thin film of peritoneal fluid, consisting of water, electrolytes, leukocytes, and antibodies. The fluid plays two main functions: it acts as a lubricant, enabling free movement of the abdominal viscera, and its antibodies fight infection. Under healthy conditions, a small volume of 5–20 mL of peritoneal fluid is physiologically present in the peritoneal cavity. Peritoneal fluid contains various types of immune cells, such as macrophages, natural killer cells, lymphocytes, eosinophils, mesothelial cells, and mast cells.[2,3] In pathological conditions, the balance between peritoneal fluid secretion and drainage is often disturbed, causing an accumulation of fluid in the peritoneal cavity known as ascites.[1] The peritoneal cavity contains resident and migratory cell populations, which play crucial roles in the local defensive response against bacterial invasion. The presence of bacteria in the peritoneal cavity triggers a number of local and systemic responses of the host not only aimed to fight the invading microorganisms but can also lead to deleterious local and systemic sequelae for the host.

Peritonitis can be divided into primary and secondary forms.

Primary peritonitis occurs either spontaneously or secondary to infection of an intraperitoneal catheter, i.e., for dialysis. It is usually caused by a single organism. Secondary peritonitis is the sequelae of a perforation of the gastrointestinal tract caused by trauma or disease or secondary to the infection of an intra-abdominal organ. While primary peritonitis is caused by a single organism, the bacteriology of secondary peritonitis is more complex. The causative bacteria originate from the gastrointestinal tract, and therefore, secondary peritonitis is always a polymicrobial infection.[4]

Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter freundii, Proteus mirabilis, Enterobacter aerogenes, Bacteroides fragilis as Gram-negative bacteria, Staphylococcus aureus, Enterococcus faecalis, Propionibacterium species, Clostridium species, Peptococcus species as Gram-positive bacteria, and yeasts are counted as common pathogens causing peritoneal infections. B. fragilis and E. coli are common pathogens in intra-abdominal infection.[5,6] The aim of the present study was to assess the bactericidal and bacteriostatic effects of the peritoneal irrigation fluid of rats on E. coli, P. aeruginosa, K. pneumoniae, C. freundii, P. mirabilis, E. aerogenes, B. fragilis as Gram-negative bacteria, and Candida albicans.

MATERIALS AND METHODS A total of 20 male Sprague–Dawley rats weighing between 250 and 300 g were used in the present study. The animals were supplied by the Laboratory of Microbiology of the Cerrahpasa Medical Faculty of the Istanbul University. The rats 388

were housed in standard cages under standard laboratory conditions with unrestricted access to a balanced pellet diet and water.

The study protocol was approved by the Ethics Committee for Animal Experimentation of Istanbul University Cerrahpasa Medical Faculty (Istanbul, Turkey), and the experiments were conducted in accordance with animal protection laws.

The animals were randomly assigned into two groups: the sham laparotomy group (group I) and the cecal ligation + perforation group (group II). After adaption, bacterial peritonitis was induced using the cecal ligation and puncture model.

The animals were anesthetized by subcutaneous injection of a combination of 25 mg/kg of ketamine hydrochloride (10% ketamine; Sanofi-Ceva GmbH, Düsseldorf, Germany) and 5 mg/kg of xylazine hydrochloride (2% Rompun; Bayer AG, Leverkusen, Germany). After weighing, shaving, and disinfecting the skin, a 3 cm midline incision was made. The cecum was filled with feces and ligated just below the ileocecal valve with a 3-0 polyglactin suture, permitting bowel continuity. The antimesenteric cecal wall was punctured with a 21-gage needle, and the bowel was replaced into the abdominal cavity.

Peritoneal fluid samples were collected for microbiological examination. The rats in both groups were then subjected to relaparotomy in sterile conditions at 2 and 4 h, respectively.

Peritoneal lavage with 1 ml of isotonic sodium chloride solution saline was repeated, and peritoneal fluid samples were extracted.

Peritoneal Fluid Peritoneal lavage was performed by allowing 1 ml of sterile saline into the peritoneal cavity using a Pasteur pipette. The fluid was collected by centrifuge tubes. The cells obtained from peritoneal lavage fluid were placed on a 1 cm3 area of Thoma and guiding slides. The cells were stained with Giemsa and then counted. Total peritoneal cells and phagocytes were counted (cells/ml). The phagocytic cells were classified, and their percentage was calculated on Giemsa-stained slides.

The fluid samples extracted at 0, 2, and 4 h were centrifuged, then passed through a Seitz filter (pore diameter 200 nm), and sterilized. A 0.1 ml of fluid containing 104 microorganisms per milliliter and 0.9 ml of filtered peritoneal fluid were mixed in a tube. The passages from this solution were inoculated into Mueller–Hinton agar at 0, 2, 4, and 24 h. The inoculates were spread over the surface of agar plates in a standard pattern, so that the quantity of bacterial growth could be determined either semi-quantitatively or relatively. After each culture was incubated at 37 °C for 48 h, the number of proliferating colonies was counted. The bacteriostatic and bactericidal effects of the peritoneal fluid on microorganisms were assessed. This procedure was repeated for each microorganism, and the fluid was extracted from the peritoneal cavity at 0, 2, and 4 h. Control cultures were performed for each group.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Ağca et al. The antibacterial effect of peritoneal fluid in experimental peritonitis

Table 1. Bactericidal effects of the peritoneal fluid samples obtained from all rats at different time points Microorganisms 0 2 4 8 24 hour hour hour hour

Escherichia coli

330 45 – – –

Pseudomonas aeruginosa 420 124 – – – Klebsiella pneumoniae 330 100 90 95 500 Candida albicans

252 184 50 30 140

Microbiology After culturing for 18 h in tryptic soy broths, E. coli, K. pneumoniae, E. aerogenes, C. freundii, P. aeruginosa, P. mirabilis, and C. albicans were isolated from feces. The microorganisms were inoculated after dilution to 104/ml using several culture techniques.

Statistical Analysis For comparison of intragroup and intergroup results, Student’s t-test and ANOVA were used, respectively. A p value <0.05 was considered as statistically significant.

RESULTS Bactericidal Activity of Peritoneal Cells In all groups, the peritoneal fluid was not effective against P. mirabilis, E. aerogenes, and C. freundii. In addition, it was observed that the proliferation of K. pneumoniae stopped for 8 h. However, it was determined that proliferation in cultures increased after 24 h. A decrease in proliferation was observed in C. albicans at the end of 4 and 8 h, and an increase in proliferation was seen at the end of 24 h. It was also observed that the proliferating colony counts of E. coli and P. aeruginosa decreased after 2 h, and there was no proliferation in subsequent cultures (Table 1, Fig. 1).

1400

Candida albicans Klebsiella pneumonia Pseudomonas aeroginosa Eschericha coli

Number of colonies

1200 1000 800 600 400 200 0

0

2.h

4.h Hours

8.h

24.h

Figure 1. Number of colonies of microorganisms at different time points.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

DISCUSSION Peritoneal infections may be mainly due to: (1) translocation of microorganisms from exogenous or endogenous flora to the sterile sides in the body as a result of organic traumas or injuries that break dermal or mucosal barriers mechanically; (2) surgical contamination, infections due to biomaterials, antimicrobial medication, or chemotherapy leading to hemostatic imbalance between the host and the commensal microflora of the host; and (3) bacterial translocation through the intact mucosal barrier of the intestines. It is known for years that anaerobic bacteria may lead to peritoneal infections. It was recorded that 37% of peritoneal infections are due to Bacteroides species; 57% are due to facultative anaerobic and aerobic Gram-negative bacilli of which 36% is E. coli alone.[7,8] In one study by Uzunköy et al.,[9] E. coli was produced in all subjects in lymphoid tissue cultures in rats with bacterial peritonitis, and in addition, P. mirabilis and K. pneumoniae were observed.

Lipopolysaccharides in the bacterial walls, yeasts (Candida, Cryptococcus, etc.), some tumor cells, parasites, and viruses activate the components of the complement system that institutes a chemotactic gradient for the polymorphonuclear leukocytes (PMNLs). The migration to the peritoneal cavity due to chemotactic factors starts in 30 min and reaches a maximum rate at 72 h. The number of peritoneal cells was counted in Thoma slides. The peak number was achieved at 6 h, and this number did not increase at 9 h; however, a decrease was recorded as time passed. Accordingly, the peritoneal fluid extracted at 6 h following the stimulation of the peritoneal membrane was preferred in the present study. Phagocytosis is a rapid response allowing approximately 3% of the bacteria to be unbound after 2 h post-inoculation.[7] Although macrophages are the primary phagocytic cells, PMNLs are the earliest set of cells drawn into the peritoneal cavity.[10] Phagocytosis is triggered by nonspecific opsonins, such as complements, fibronectin, or specific antibodies present in the peritoneal fluid. Complements play an important role of body defense in the early phase of infections where antibodies are not formed yet.[11] Lysozymes break the bonds between N-acetylmuramic acid and N-acetylglucosamine in Gram-positive bacteria. The peptidoglycan and muramic acid present in the cell walls of Gram-negative bacteria are protected by an outermost membrane, thus the effect of lysozyme being minimum.[12] Histamine and other vasoactive substances released from peritoneal mast cells cause dilation of the capillaries in the peritoneal cavity. An increased permeability leads to an accumulation of fluid rich in complements, immunoglobulins, fibrins, and thrombotic factors. Bergman et al.[13] reported that cell-free amniotic fluid obtained from 28 healthy women is effective on Gram-negative and Gram-positive bacteria and yeasts. This bacteriostatic or bactericidal effect might depend on complements, thermostability, and maybe some other factors since lysozyme in the amniotic fluid solely cannot be responsible for the antimicrobial activity. In a study comparing the antibacterial activity of peritoneal fluid obtained from 28 women who underwent laparoscopy with the acid fluid obtained from 11 patients with various pathological conditions, 389

Ağca et al. The antibacterial effect of peritoneal fluid in experimental peritonitis

the bactericidal and bacteriostatic activities in both types of lavage were predominantly against Gram-negative bacilli—E. coli, P. mirabilis, and B. fragilis.[14] In our study, we found that peritoneal fluid had no effect on C. freundii, P. mirabilis, and E. aerogenes; however, peritoneal fluid was found to be bactericidal for E. coli and P. aeruginosa and bacteriostatic for K. pneumoniae and C. albicans.

The cells and substances in the peritoneum prevent bacterial contamination and peritoneal inflammation. The main target in managing peritonitis is to control sepsis and eliminate contamination sources. The contamination of the peritoneal cavity with bacteria can be via endogenous route or exogenous route. The mortality of peritonitis is still high despite advances in medicine. Overall, mortality in secondary peritonitis varies between 13% and 18% and between 0% and 46% according to contamination source and age, respectively. Control of sepsis and removal of contamination sources and peritoneal debris are the principal goals of peritonitis treatment. Removing or decreasing the debris is possible using peritoneal lavage that can be performed in several ways. There is no doubt on the importance of sepsis and removal of the contamination source. However, the effectivity of peritoneal lavage in the management of peritonitis is rather doubtful. It is accepted that short-term peritoneal lavage is useful in the treatment of peritonitis as it decreases the microbial load.[15] In the present study, the bactericidal activity of the peritoneal fluid decreases due to peritoneal lavage in the early phase and returns to normal after 4 h. The bactericidal effect of the peritoneum should be taken into consideration, and it is necessary to prevent the disruption of the peritoneal defense mechanism. We can claim that continuous or intermittent peritoneal lavage will not be beneficial. On the other hand, it cannot disrupt the protective mechanisms as the bactericidal activity of the peritoneum is considered to be important in the early phases of peritonitis.

Conflict of interest: None declared.

REFERENCES 1. Capobianco A, Cottone L, Monno A, Manfredi AA, Rovere-Querini P. The peritoneum: healing, immunity, and diseases. J Pathol 2017;243:137–47.

2. Van Baal JO, Van de Vijver KK, Nieuwland R, van Noorden CJ, van Driel WJ, Sturk A, et al. The histophysiology and pathophysiology of the peritoneum. Tissue Cell 2017;49:95–105.

3. Gazvani R, Templeton A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction 2002;123:217–26.

4. Hau T. Peritoneal Defense Mechanisms. Turk J Med Sci 2003;33:131–4.

5. Swenson RM, Lorber B, Michaelson TC, Spaulding EH. The bacteriology of intra-abdominal infections. Arc Surg 1974;109:398–9.

6. Swenson RM, Lorber B. Clindamycin and Carbenicillin in treatment of patients with intraabdominal and female genital tract infections. J Infect Dis 1977;135 Suppl:S40–5.

7. Baron EJ, Fniegold SM. Bailey and Scott’s Diagnostic Microbiology. 8th ed. Missouri: C.V. Mosby; 1990. p. 363–407.

8. Koneman EW, Allen SD, Janda WM, Schreckenberg PC, Winn WC. Diagnostic Microbiology. 5 th ed. New York: Lippincott; 1997. p. 171–309.

9. Uzunköy A, Ozbilge H, Horoz M. The influence of omentectomy on bacterial clearance: an experimental study. Ulus Travma Acil Cerrahi Derg 2009;15:541–5.

10. Kuraoka S, Campeau JD, Nakamura RM, diZerega GS. Modulation of postsurgical macrophage function by early postsurgical polymorphonuclear leukocytes. J Surg Res 1992;53:245–50.

11. Pascual M,French LE. Complement in human diseases: looking towards the 21st century. Immunol Today 1995;16:58–61.

12. Bernard E, Rolain T, Courtin P, Guillot A, Langella P, Hols P, et al. Characterization of O-acetylation of N-acetylglucosamine: a novel structural variation of bacterial peptidoglycan. J Biol Chem 2011;286:23950–8.

13. Bergman N, Bercovici B, Sacks T. Antibacterial activity of human amniotic fluid. Am J Obstet Gynecol 1972;114:520–3.

14. Michel J, Bercovici B, Sacks T. Comparative studies on the antimicrobial activity of peritoneal and ascitic fluids in human beings. Surg Gynecol Obstet 1980;151:55–7.

15. Sayek I, Abbasoğlu O, Altaca G, Akalın E. The effect of peritoneal lavage on survival in experimentalfecal peritonitis and peritoneal fluid bactericidal activity. Surg Res Comm 1990;7:277–82.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel peritonitte peritoneal sıvının antibakteryel etkisi Dr. Birol Ağca,1 Dr. Ahmet Yalın İşcan,1 Dr. Erdal Polat,2 Dr. Kemal Memişoğlu1 1 2

İstanbul Sağlık Bilimleri Üniversitesi Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Mikrobiyoloji Anabilim Dalı, İstanbul

AMAÇ: Çalışmamızda deneysel peritonit oluşturulan sıçanlarında, periton sıvısının bazı gram negatif ve Candida albicans üzerine olan etkisi araştırıldı. Çalışmanın temel amacı karın içi enfeksiyonlara neden olan mikroorganizmalar üzerine periton sıvısının etkisini anlamaktır.

GEREÇ VE YÖNTEM: Bu çalışmada 250-300 g ağırlığında 20 erkek Spraque-Dawley sıçanı kullanıldı. Sıçanlar rastgele 10 hayvandan oluşan iki gruba ayrıldı. Ameliyat prosedürleri steril koşullar altında yapıldı. Grup I’de kontrol laparotomisi yapıldı. Grup II’de çekumun distal kısmı bağlandı ve çekum perforasyonu yapıldı. Deneklerden 2. ve 4. saatte anestezi altında laparotomi yapılarak peritoneal sıvı örnekleri Pasteur pipet kullanılarak alındı.

BULGULAR: Periton sıvısı, C. freundii, P. Mirabilis ve E. aerogenes’e etkisizdi. Sekiz saat boyunca K. pneumoniae üremesini engelledi, ayrıca 24 saat sonra alınan pasajlarda büyüme önemli ölçüde arttığı görüldü. C. Albicans üremesi ise 4 ve 8 saat sonra alınan pasajlarda azaldı ve 24 saat sonra ise arttı. E. coli ve P. aeroginosa kolonilerinin sayısının 2 saat sonraki alınan pasajlarda artmadığı ve üreme olmadığı saptandı.

TARTIŞMA: E. coli ve P. aeruginosa’nın çoğalan koloni sayıları 2 saat sonra azaldı ve sonraki kültürlerde çoğalma yoktu. Periton sıvısı, uygun koşullar altında bakterisidal bir etki gösterir. Karın içi enfeksiyonlarda ana patojen olan E. coli’ye karşı peritoneal bakterisidial etkinlik göstermektedir.

Anahtar sözcükler: Gram-negatif bakteri; peritoneal savunma; periton sıvısı.

Ulus Travma Acil Cerrahi Derg 2018;24(5):387-390

390

doi: 10.5505/tjtes.2018.10452

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

EXPERIMENTAL STUDY

Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury Yılmaz Ünal, M.D.,1 Berkay Küçük, M.D.,1 Salih Tuncal, M.D.,1 Koray Koşmaz, M.D.,1 Nadir Turgut Çavuşoğlu, M.D.,1 Kemal Kısmet, M.D.,1 Mehmet Şeneş, M.D.,2 Pınar Celepli, M.D.,3 Murat Durak, M.D.,2 Sema Hücümenoğlu, M.D.3 1

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

2

Department of Biochemistry, Ankara Training and Research Hospital, Ankara-Turkey

3

Department of Pathology, Ankara Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: This study investigates the protective effect of calcium dobesilate (CaDob), an effective antioxidant and anti-inflammatory drug, on experimental liver ischemia-reperfusion injury (IRI).

METHODS: Forty rats were divided into four groups. In Group 1, (sham), only hepatic pedicle was induced. In Group 2 (control), hepatic pedicle was reperfused for 90 min after being clamped for 60 min. No treatment was given in Group 1 and 2. In Group 3 (perioperative CaDob), 100 mg/kg CaDob was given 2 hours prior to the operation in which hepatic pedicle was reperfused for 90 min following a 60-min clamp. In Group 4 (preoperative CaDob), after 100 mg/kg/day CaDob was given for 10 days before the operation, hepatic pedicle was clamped for 60 min and reperfused for 90 minutes. At the end of these procedures, blood and liver tissue samples were collected for biochemical and histopathological assessment.

RESULTS: Liver function tests and tissue oxidative stress parameters were significantly lower in the preoperative and perioperative treatment groups than the control group. Furthermore, it was observed that histopathological injury in the control group significantly decreased in both perioperative and preoperative treatment groups.

CONCLUSION: Calcium dobesilate demonstrated a significant hepatoprotective effect in terms of its antioxidant and anti-inflammatory effects.

Keywords: Calcium dobesilate; experimental; histopathology; ischemia reperfusion; liver; oxidative stress.

INTRODUCTION Ischemia reperfusion injury (IRI) is a clinical situation with significant effects on multiple organs including the liver, heart, intestine, kidney and brain.[1] Hepatic IRI is an important problem that arises during liver resection, liver trauma operation, organ transplantation and reconstructive vascular surgery and it is a life-threatening situation.[2] Moreover, apart from surgical interventions, hepatic IRI can also appear due to hemorrhagic shock and sepsis.[3] During the ischemic period, cellular damage is observed in tissues exposed to ischemia due to oxygen deprivation. Reactive oxygen species (ROS)

are released from ischemic tissues upon the return of blood flow (reperfusion) and this leads to more serious organ damage.[4] In hepatic IRI pathogenesis; numerous complex and multifactorial reasons play a role, such as microcirculation dysfunction, the activation of Kuppfer cells, apoptosis, sinusoidal endothelium cell dysfunction, oxidative stress and inflammation.[5] Hepatic IRI leads to serious hepatic pathologic reactions resulting in cellular death and organ dysfunction.

Different mechanisms play a part in hepatic cellular damage during ischemia and also after reperfusion. Although it is not known which mechanism is important in the pathogenesis of ischemic cellular damage, oxygen deprivation is the most

Cite this article as: Ünal Y, Küçük B, Tuncal S, Koşmaz K, Çavuşoğlu NT, Kısmet K, et al. Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury. Ulus Travma Acil Cerrahi Derg 2018;24:391-397.

Address for correspondence: Yılmaz Ünal, M.D. Ankara Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara, Turkey Tel: +90 312 - 595 30 00 E-mail: yilmazunal66@mynet.com Ulus Travma Acil Cerrahi Derg 2018;24(5):391-397 DOI: 10.5505/tjtes.2018.33238 Submitted: 19.04.2018 Accepted: 13.08.2018 Online: 20.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

391

Ünal et al. Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury

commonly suspected factor. During ischemia, multiple different cellular and subcellular dysfunctions in cell membranes and decreased protein synthesis arise. Although several experimental studies have been carried out to prevent or decrease hepatic IRI, there is still no agent commonly used in clinical practice.[6–8] Calcium dobesilate is a pharmacological agent used in the treatment of chronic venous stasis, diabetic retinopathy and hemorrhoidal diseases due to its angioprotective and antioxidant properties.[9] Moreover, it has been shown in many studies that calcium dobesilate corrects capillary dysfunctions, decreases free oxygen radicals, increases nitric oxide synthase and prevents desquamation in endothelium cells.[10,11] In experimental studies, calcium dobesilate has been shown to have protective effects against ischemia reperfusion injury in various organs like the heart, lungs and intestines. The antioxidant and anti-inflammatory properties of calcium dobesilate are attributed to reduced lipid pre-oxidation caused by free oxygen radicals and a decreased release of inflammatory cytokines, such as platelet activating factor (PAF).[12–14] However, there are no studies in the present literature that investigate the effect of calcium dobesilate on hepatic IRI. As oxidative stress and inflammation are the main mechanisms responsible for tissue damage in ischemia-reperfusion events, this study was designed to investigate the effect of calcium dobesilate, which has antioxidant and anti-inflammatory effects, on hepatic IRI.

MATERIALS AND METHODS The study was performed with the endorsement of the Animal Ethics Committee at Ankara Training and Research Hospital and according to the principles of the National Guidelines for the Use and Care of Laboratory Animals.

Animals The study included 40 adult, female Wistar Albino rats in total, each weighing 225±25 gr. The rats were stored in wire cages at a fixed temperature of 21°C±2°C with a 12 hour light/dark cycle. The rats in the sample were made to fast for 12 hours and their access to water was stopped 2 hours prior to anesthesia. No rats received parenteral or enteral antibiotics throughout the experiment. The anesthesia and surgical intervention were performed under sterile conditions by the same team. The rats were divided into 4 groups randomly, each consisting of 10 rats. All rats were anesthetized intramuscularly with 50 mg/kg of ketamine hydrochloride (Ketalar®; Parke-Davis, Istanbul, Turkey) and 5 mg/kg Xylazine (Rompun®; Bayer, Istanbul, Turkey).

Experimental Groups and Surgical Procedure In all rats, the abdomen was entered with a midline incision and the following procedures were applied to the groups. In 392

Group 1(sham), only hepatic pedicle was induced. In Group 2(control), ischemia was performed by clamping the hepatic pedicle for 60 min. Following the ischemic period, the clamp was opened and 90 min reperfusion of the liver was provided. In Group 1 and Group 2, no treatment was applied.

In Group 3 (perioperative CaDob), 100 mg/kg calcium dobesilate (Doxium® Abdi Ibrahim, Istanbul, Turkey) was given 2 hours before the operation by using an orogastric tube. Then, ischemia was carried out by clamping the hepatic pedicle for 60 min and reperfusion was carried out for 90 min by opening the clamp. In Group 4 (preoperative CaDob), 100 mg/kg/day calcium dobesilate was given for 10 days before the operation through an orogastric tube. At the end of this procedure, the hepatic pedicle was clamped for 60 min and then reperfusion was carried out for 90 min by opening the clamp.

After the completion of these procedures, all the rats were euthanized using an overdose of ketamine. Following the laparotomy, blood and liver tissue samples were collected for biochemical and histopathological analyses.

Biochemical Analyses Evaluation of the liver functions in the serum was carried out in the Biochemistry Department of Ankara Training and Research Hospital. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) were measured by use of a chemistry analyzer for clinical purposes (Beckman Coulter 5800) which uses Beckman Coulter commercial kits.

The parameters of oxidative stress were evaluated at the Biochemistry Department of Ankara Training and Research Hospital. Liver tissues were kept at -80°C until the day of the analysis. The total sulfhydryl (SH), malondialdehyde (MDA) and fluorescent oxidation products (FOP) levels were determined. MDA acts as a lipid peroxidation indicator and is a known tissue injury index. The levels of MDA were measured through the fluorometric method, in line with the description of Wasowicz et al.[15] Following the reaction that occurs between thiobarbituric acid (TBA) and MDA, the reaction product was isolated in butanol. Following this, a spectrofluorometrical measurement was carried out at a wavelength of 547 nm for emission and 525 nm for excitation. The standard was designated as a 0–5 µmol/L 1,1’,3,3’ tetraethoxypropane solution. 50 µL homogenate was introduced into 10 ml tubes made of glass, each with 1 ml of distilled water in order to measure MDA levels in tissue. Then, a 1 mL solution which contained 29 mmol/L TBA was added to acetic acid and mixed. Following this, the samples were exposed to heat of between 95° and 100°C for a period of 1 hour using a water bath. After cooling the heated samples, they were mixed with 25 µL of 5 mol/L hydrochloric acid (HCL) and agitation was used for a period of 5 min to extract the mixture of the reaction using 3.5 mL n-butanol. Following the separation of the butanol phase through centrifugation for 10 min at 1500 Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Ünal et al. Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury

Table 1. Suzuki scoring system Grade Sinusoidal congestion

Necrosis

Vacuolization

0 None None 1

Mild

None

Simple cell necrosis

2 Moderate 0–30%

Mild Moderate

3 Severe 30–60% Severe 4

Excessive

Over 60%

Excessive

g, a fluorometer (HITACHI F-2500) was used to measure the fluorescence in the butanol extract at 547 nm and 525 nm wavelengths for emission and excitation, respectively. Solutions of 0–5 µmol/L 1,1’,3,3’ tetraethoxypropane were utilized as standard. The levels of MDA were shown as nmol/g.

It is known that injured tissues have lower total SH levels than normal ones. The measurement of total SH was carried out in a spectrophotometrical way by means of the Sedlak and Lindsay[16] method. 250µL of aliquots taken from the supernatant fraction of the homogenized tissue were stirred in tubes of 5 mL using 50µL of 0.01 M 5,5’’-dithiobis (2 nitrobenzoic acid) (DTNB) and 750 µl of 0.2 M Tris buffer, pH 8.2. 3950 µl absolute methanol was inserted in order to have a final mixture of 5 ml. Also, a sample blank (No DTNB) and a reagent blank (No sample) were obtained in a comparable way. Rubber stoppers were used to close the tubes and color was permitted to develop for a period of 15 min in the reaction mixture. The resultant mixtures were then put into a centrifuge for 15 min at about 3,000 g at normal room temperature. The values of absorbance found in supernatant fractions were identified by means of spectrophotometer at 412 nm.[16] Homogenized tissues were isolated using ethanol-ether (3/1, v/v) for FOP measurements; then these tissues were evaluated through a spectrofluorometer at wavelengths of 360 and 430 (wavelengths for excitation/emission).[17]

Histopathological Analysis The analysis of histopathology was executed at Ankara

Training and Research Hospital, Pathology Department. The liver tissue samples for light microscope analysis were fixed in a 10% formaldehyde solution for 24 hours. Following the stages of ethanol dehydration and xylene classification, the tissue samples were embedded in blocks of paraffin. 4µmthick sections were cut from the blocks of paraffin with a Leica RM 2155 RT microtome. These sections of tissues were stained using hematoxylin & eosin and then analyzed. The histopathological examination was made using a blinded study carried out by a pathologist using a light microscope (Olympus BX51TF). The histopathological evaluation was completed semi-quantitatively with the modified Suzuki Scoring System[18] from 0 to 4 with respect to sinusoidal congestion, liver cell vacuolization and hepatocyte necrosis. The modified Suzuki Scoring System is given in Table 1.

Statistical Analysis The Statistical Analysis Package for Social Sciences (SPSS version 15.0) was used to execute data analysis (SPSS Inc., Chicago, IL, USA). According to the analysis, all the variables showed a normal distribution around the average value. The data were given in the form of mean±standard deviation.

Either the Kruskal-Wallis variance analysis or the ANOVA (One-way analysis of variance) was made use of in order to assess the differences across the groups. In cases when the p value had a statistical significance, the Mann-Whitney U multivariance analysis was employed to find out the differences across the groups. It was accepted that the p<0.05 level was statistically significant.

RESULTS Liver Function Tests The average levels of liver functions (ALT, AST, GGT, ALP) are given in Table 2. A significant difference (p<0.05) was found between the sham and the other three groups in all the parameters (except for the ALP and GGT values in the preoperative CaDob group). The liver functions had the highest values in the control group. The perioperative and preoperative CaDob treatment lowered these high levels significantly compared to the control group (p<0.05). Although the levels in the preoperative CaDob group were significantly lower

Table 2. The average levels of liver functions Groups Group 1 (Sham) Group 2 (Control)

AST (U/L)

ALT (U/L)

GGT (U/L)

ALP (U/L)

352.90±108.02a,b,c 173.70±98.90a,b,c 1.62±0.74a,b 96.20±17.40a,b 2006.66±422.d,e 1524.11±265.01d,e 7.40±3.47d,e 186.80±36.57d,e

Group 3 (Periop CaDob)

1452.66±680.61

1025.75±421.27

3.25±1.58

129.87±32.57

Group 4 (Preop CaDob)

1369.37±429.77

994.62±513.35

3.00±1.73

118.00±31.76

Significantly different, sham vs control (p<0.05), bsignificantly different, sham vs periop CaDob (p<0.05), csignificantly different, sham vs preop CaDob (p<0.05), dsignificantly different, control vs periop CaDob (p<0.05), esignificantly different, control vs preop CaDob (p<0.05).

AST: Aspartate aminotransferase; ALT: Alanin aminotransferase; GGT: Gamma glutamyl transpeptidase; ALP: Alkaline phosphatase. a

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

393

Ünal et al. Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury

Table 3. The average levels of oxidative stress parameters Groups

MDA (nmol/gr protein)

Total SH (µmol/gr protein)

FOP (FOP/gr protein)

Group 1 (Sham)

24.90±8.59a,b 122.47±17.35a 100.93±9.05a,b,c

Group 2 (Control)

55.61±8.26d,e 87.29±8.01d,e 193.83±29.45d,e

Group 3 (Periop CaDob)

34.63±9.52

116.36±28.30

140.29±24.82

Group 4 (Preop CaDob)

28.96±5.23

120.89±10.83

131.51±39.98

a Significantly different, sham vs control (p<0.05), bsignificantly different, sham vs periop CaDob (p<0.05), csignificantly different, sham vs preop CaDob (p<0.05), dsignificantly different, control vs periop CaDob (p<0.05), esignificantly different, control vs preop CaDob (p<0.05). MDA: Malondialdehyde; SH: Sulfydryl; FOP: Fluorescent oxidation products.

Table 4. The average histopathological scores of the groups Groups

Congestion Vacuolisation Necrosis

Group 1 (Sham)

0.50±028a,b 0.00±0.00 0.00±0.00

Group 2 (Control)

2.90±0.56c,d 0.20±0.11 0.00±0.00

Group 3 (Periop CaDob)

1.88±0.78e 0.00±0.00 0.00±0.00

Group 4 (Preop CaDob)

0.50±0.31

0.05±0.02

0.00±0.00

Significantly different, sham vs control (p<0.05), bsignificantly different, sham vs periop CaDob (p<0.05), csignificantly different, control vs periop CaDob (p<0.05), dsignificantly different, control vs preop CaDob (p<0.05), esignificantly different, periop vs preop CaDob (p<0.05).

a

than the perioperative CaDob group, no statistical difference was found between these two groups (p>0.05).

Oxidative Stress Parameters The average levels of oxidative stress parameters (MDA, total SH, FOP) are presented in Table 3. Significant differences were found in all the parameters between the sham and the control group (p<0.05). A significant difference was found in MDA and FOP between the sham and the perioperative CaDob group and in FOP between the sham and the preoperative CaDob group (p<0.05).

The highest levels of MDA and FOP and the lowest levels of total SH were detected in the control group. It was determined that preoperative and perioperative CaDob treatment significantly decreased the MDA and FOP levels and significantly increased the total SH level (p<0.05). Although the levels of MDA and FOP were lower and the total SH levels were higher in the preoperative CaDob group compared to the perioperative CaDob group, no statistical differences were found between these two groups (p>0.05).

Histopathological Results The average histopathological scores of the groups are given in Table 4. The congestion scores of the sham group were significantly lower than the control and perioperative groups (p<0.05). The highest congestion scores were in the control group and it was determined that perioperative and preoperative calcium dobesilate treatment significantly decreased 394

the congestion scores (p<0.05). There was also a significant difference in terms of congestion scores between the perioperative and preoperative calcium dobesilate groups (p<0.05).

While there was no significant difference between the groups with respect to vacuolization (p>0.05), necrosis was not detected in any groups.

Typical histopathological changes are given in Figure 1a, b and c. It was seen that the portal areas and lobules had a regular structure in the sham group. Inflammation and sinusoidal congestion were not observed (Fig. 1a). Intense sinusoidal congestion and inflammatory cell infiltration were observed around the central vein in the control group (Fig. 1b). It was seen that sinusoidal congestion and inflammation decreased in the groups in which preoperative and perioperative CaDob were given compared to the control group (Fig. 1c).

DISCUSSION Ischemia is the inadequate supply of blood as a result of decreased or obstructed blood flow to tissues and organs due to certain reasons. Oxygen deprivation in tissues exposed to ischemia for a certain period of time results in tissue damage. Restoration of blood flow following ischemia is called reperfusion and during this period, tissue damage caused by ischemia further increases because of the release of reactive oxygen species (ROS) from ischemic tissues.[4] This is commonly referred to as IRI and is a serious clinical issue concerning multiple vital organs such as the liver, heart, intestines and kidney.[1] It is thought that the local and systemic effects created by IRI contributes to high morbidity and mortality in Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Ă&#x153;nal et al. Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury

(a)

(b)

(c)

Figure 1. (a) In the sham group, portal areas and lobules are in a regular structure with no inflammation or sinusoidal congestion (x100, x200). (b) In the control group, there is an intense sinusoidal congestion and inflammation around the central vein in the liver tissue.(x100, x200). (c) In CaDob groups, the sinusoidal congestion was decreased significantly when compared with control group (x200).

numerous clinical situations like organ transplantation, myocardial infarction, cerebrovascular diseases, major surgical interventions and hemorrhagic shock.[19,20] Hepatic IRI is an important clinical situation which emerges during liver resection, liver trauma operations, liver transplantation and reconstructive vascular surgery.[2] In addition to surgical interventions, hepatic IRI can also appear in such situations as hemorrhagic shock, resuscitation and sepsis.

[3] Ischemia is induced in major liver operations through hepatic pedicle clamping to minimize blood loss. Afterwards, the reperfusion period begins by declamping. However, this method may result in hepatic IRI.[21] Numerous complex and multifactorial causes have a role in hepatic IRI pathogenesis, such as microcirculation dysfunction, the activation of Kuppfer cells, apoptosis, sinusoidal endothelium cell dysfunction, oxidative stress and inflamUlus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

mation.[5] Microcirculation dysfunction develops in the liver as a result of all these events. The neutrophils and the activation of Kupffer cells lead to the release of free oxygen radicals and inflammatory cytokines. Free oxygen radicals play the most important role in IRI physio-pathogenesis. A small number of free oxygen radicals are produced during metabolism under normal circumstances and thus all aerobic organisms are exposed to physiologic oxidative stress.

Normally these radicals are immediately eliminated by the antioxidant defense mechanisms of the body. However, since the intrahepatic defense systems are impaired during hepatic IRI, the excessive numbers of free oxygen radicals produced cannot be removed effectively. Therefore, these free oxygen radicals lead to the peroxidation of unsaturated fatty acids in cell membranes. Moreover, they are cross-linked to biological macromolecules like DNA, RNA and proteins and change their structures, thus resulting in cell death and tissue damage.[22,23] 395

Ünal et al. Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury

Malondialdehyde (MDA) is a byproduct of lipid peroxidation and is a sensitive indicator of oxidative stress damage.[15,24] Additionally, it is also known that injured tissues have lower total SH levels than normal ones.[16] In this study, significantly lower levels of MDA and FOP, and also higher levels of total SH were observed in the treatment groups.

Numerous experimental studies have been carried out in order to decrease the harmful effects of hepatic IRI.[6–8,25] However, there is still no pharmacological agent routinely used in clinical practice.

In a study designed by Tanrikulu et al.,[6] it was determined that diosmin treatment significantly reduced oxidative stress parameters and liver enzyme levels in an experimental IRI model in rats. Furthermore, diosmin ameliorated the histopathological abnormalities caused by hepatic IRI. In another experimental liver IRI model carried out by Deng et al.,[8] it was shown that melatonine effectively decreased both the levels of liver functions and free oxygen radicals.

Barlas et al.[25] investigated the effect of erdosteine on experimental liver IRI and found that erdosteine treatment relieved histopathological findings compared to the control group.

Moreover, it was determined that this treatment improved liver function values and oxidative stress parameters.

Calcium dobesilate, a synthetic sulfobenzene derivative, is an angio-protective and venotonic pharmacological agent used orally. It is widely used in clinical practice in the treatment of chronic venous stasis, hemorrhoidal diseases and diabetic retinopathy.[9] Moreover, it has been shown in various studies that calcium dobesilate has antioxidant, antiaggregant and endothelium function regulating effects. It reduces capillary permeability and blood viscosity with its antiaggregant and antioxidant effects and increases lymphatic drainage. These studies have shown that calcium dobesilate increases endothelial nitric oxide synthesis through nitric oxide synthetase activation.[10,11] Calcium dobesilate carries out its antiaggregant activity through cyclic adenosine monophosphate (cAMP) with the activation of the adenylate cyclase enzyme.

Furthermore, it performs an antioxidant effect by reducing the release of platelet activating factor (PAF) from platelets and by eliminating free oxygen radicals that activate endothelium damage.[26,27] Seker et al.[14] investigated the effects of calcium dobesilate on intestinal IRI in rats and they determined that calcium dobesilate increased the total antioxidant capacity, reduced tissue damage histopathologically and decreased both the serum and tissue oxidative stress index.

In another experimental study performed by Cihan Ozbek et al.,[12] it was found that calcium dobesilate had a cardioprotective effect on rat hearts perfused with calcium dobesilate.

396

Garay et al.[27] revealed that in addition to its strong antioxidant properties, calcium dobesilate improved diabetic endothelium dysfunction, reduced apoptosis and decreased vascular cell proliferation. In another study by Jafarey et al.,[28] it was found that calcium dobesilate protected rats against nephrotoxicity related to gentamicin. Brunet et al.[29] determined that calcium dobesilate reduced microvascular permeability increased by free oxygen radicals in rats. Moreover, they concluded that this angioprotective effect might be related to the antioxidant activity of calcium dobesilate.

Based on these studies which show the strong antioxidant properties and the positive effects of calcium dobesilate on IRI, the present study investigated its protective effects on experimental liver IRI. When the results of this study are examined, it can be seen that preoperative and perioperative calcium dobesilate treatment significantly reduced sinusoidal congestion and inflammation in liver tissue compared to the control group. Additionally, serum liver functions and tissue oxidative stress parameters were significantly decreased in the treatment groups. The results in the preoperative treatment group were more positive than the perioperative treatment group but the difference between these two groups was not statistically significant.

Conclusion To the best of our knowledge, this is the first study in the literature that investigates the effect of calcium dobesilate on hepatic IRI. In our study, perioperative and preoperative calcium dobesilate treatment showed a strong hepatoprotective effect due to its antioxidant and anti-inflammatory properties. According to the results of this study, calcium dobesilate can be used as a protective agent for IRI in both emergent and elective liver surgery.

Conflict of interest: None declared.

REFERENCES 1. McCord JM. Oxygen-derived free radicals in postischemic tissue injury.

N Engl J Med 1985;31:159–63.

2. Glantzounis GK, Salacinski HJ, Yang W, Davidson BR, Seifalian AM. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review. Liver Transpl 2005;11:1031–47.

3. Powner DJ. Factors during donor care that may affect liver transplantation outcome. Prog Transplant 2004;14:241–9.

4. Pantazi E, Bejaoui M, Folch-Puy E, Adam R, Roselló-Catafau J. Advances in treatment strategies for ischemia reperfusion injury. Expert Opin Pharmacother 2016;17:169–79.

5. Selzner N, Rudiger H, Graf R, Clavien PA. Protective strategies against ischemic injury of the liver. Gastroenterology 2003;125:917–36.

6. Tanrikulu Y, Sahin M, Kismet K, Kilicoglu SS, Devrim E, Tanrikulu CS, et al. The protective effect of diosmin on hepatic ischemia reperfusion injury: an experimental study. Bosn J Basic Med Sci 2013;13:218–24.

7. Yucel AF, Pergel A, Aydin I, Alacam H, Karabicak I, Kesicioglu T, et al.

Effect of infliximab on acute hepatic ischemia/ reperfusion injury in rats.

Int J Clin Exp Med 2015;8:21287–94.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Ünal et al. Assessment of the effect of calcium dobesilate in experimental liver ischemia-reperfusion injury 8. Deng WS, Xu Q, Liu YE, Jiang CH, Zhou H, Gu L. Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury. Exp Ther Med 2016;11:1955–60.

9. Allain H, Ramelet AA, Polard E, Bentué-Ferrer D. Safety of calcium dobesilate in chronic venous disease, diabetic retinopathy and haemorrhoids. Drug Saf 2004;27:649–60.

10. Ruiz E, Lorente R, Tejerina T. Effects of calcium dobesilate on the synthesis of endothelium-dependent relaxing factors in rabbit isolated aorta.

Br J Pharmacol 1997;121:711–6.

11. Suschek C, Kolb H, Kolb-Bachofen V. Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells. Br J Pharmacol 1997;122:1502–8.

12. Cihan Ozbek I, Arslan C, Cantürk E, Süzer O. The effects of calcium dobesilate on the mechanical function of rat hearts. J Cardiovasc Surg 2009;50:395–401.

13. Bozkurt AK, Konukoğlu D, Ustündağ N, Yüceyar L, Mayda AS. Calcium dobesilate ameliorates lung injury following lower limb ischemia/reperfusion. Drugs Exp Clin Res 2002;28:127–32.

14. Seker A, Bardakci O, Eryilmaz S, Kocarslan S, Incebiyik A, Yucel Y, et al.

Does calcium dobesilate protect against intestinal ischemia-reperfusion injury induced in rats? Eur Rev Med Pharmacol Sci 2016;20:2168–73.

15. Wasowicz W, Nève J, Peretz A. Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem 1993;39:2522–6.

16. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968;25:192–205.

17. Wu T, Willett WC, Rifai N, Rimm EB. Plasma fluorescent oxidation products as potential markers of oxidative stress for epidemiologic studies. Am J Epidemiol 2007;166:552–60.

18. Suzuki S, Toledo- Pereyra LH, Rodriguez FJ, Cejalvo D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion in-

jury. Modulating effects of FK506 and cyclosporine. Transplantation 1993;55:1265–72.

19. Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg 2001;181:160–6.

20. Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:G15–26.

21. Jin LM, Jin SF, Liu YX, Zhou L, Xie HY, Yan S, et al. Ischemic preconditioning enhances hepatocyte proliferation in the early phase after ischemia under hemi-hepatectomy in rats. Hepatobiliary Pancreat Dis Int 2012;11:521–6.

22. Elias-Miró M, Jiménez-Castro MB, Rodés J, Peralta C. Current knowledge on oxidative stress in hepatic ischemia/reperfusion. Free Radic Res 2013;47:555–68.

23. van Golen RF, van Gulik TM, Heger M. Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury. Free Radic Biol Med 2012;52:1382–402.

24. Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress.

Nutr Metab Cardiovasc Dis 2005;15:316–28.

25. Barlas AM, Kismet K, Erel S, Kuru S, Cavusoglu T, Senes M, et al. Erdosteine ameliorates the harmful effects of ischemia-reperfusion injury on the liver of rats. Acta Cir Bras 2017;32:796–806.

26. Tejerina T, Ruiz E. Calcium dobesilate: pharmacology and future approaches. Gen Pharmacol 1998;31:357–60.

27. Garay RP, Hannaert P, Chiavaroli C. Calcium dobesilate in the treatment of diabetic retinopathy. Treat Endocrinol 2005;4:221–32.

28. Jafarey M, Changizi Ashtiyani S, Najafi H. Calcium dobesilate for prevention of gentamicin-induced nephrotoxicity in rats. Iran J Kidney Dis 2014;8:46–52.

29. Brunet J, Farine JC, Garay RP, Hannaert P. Angioprotective action of calcium dobesilate against reactive oxygen species-induced capillary permeability in the rat. Eur J Pharmacol 1998;358:213–20.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel karaciğer iskemi-reperfüzyon hasarında kalsiyum dobesilatın etkisinin değerlendirilmesi Dr. Yılmaz Ünal,1 Dr. Berkay Küçük,1 Dr. Salih Tuncal,1 Dr. Koray Koşmaz,1 Dr. Nadir Turgut Çavuşoğlu,1 Dr. Kemal Kısmet,1 Dr. Mehmet Şeneş,2 Dr. Pınar Celepli,3 Dr. Murat Durak2 Dr. Sema Hücümenoğlu3 1 2 3

Ankara Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara Ankara Eğitim ve Araştırma Hastanesi, Biyokimya Kliniği, Ankara Ankara Eğitim ve Araştırma Hastanesi, Patoloji Kliniği, Ankara

AMAÇ: Bu çalışmada, etkili bir antioksidan ve antienflamatuvar ilaç olan kalsiyum dobesilatın (CaDob) deneysel karaciğer iskemi-reperfüzyon hasarı (IRI) modelinde koruyucu etkisi araştırıldı.

GEREÇ VE YÖNTEM: Kırk sıçan dört gruba ayrıldı. Grup 1’de (sham), sadece hepatik pedikül mobilize edildi. Grup 2’de (kontrol), hepatik pedikül 60 dk klemplendikten sonra 90 dakika süreyle reperfüze edildi. Grup 1 ve 2’de ek bir tedavi uygulanmadı. Grup 3’te (ameliyat sürecinde CaDob), operasyondan iki saat önce 100 mg/kg CaDob verildi, 60 dakika iskemi sonrası 90 dakika boyunca reperfüze edildi. Grup 4’te (ameliyat öncesi CaDob), operasyondan önceki 10 gün boyunca 100 mg/kg/gün CaDob verildikten sonra, hepatik pedikül 60 dakika boyunca klemplendi ve 90 dakika süreyle reperfüze edildi. İşlemlerin sonunda biyokimyasal ve histopatolojik değerlendirme için kan ve karaciğer dokusu örnekleri alındı.

BULGULAR: Ameliyat öncesi ve ameliyat sürecinde tedavi gruplarında karaciğer fonksiyon testleri ve doku oksidatif stres parametreleri kontrol grubuna göre anlamlı olarak düşüktü. Ayrıca, kontrol grubundaki histopatolojik hasarın, hem ameliyat sürecinde hem de ameliyat öncesi tedavi gruplarında anlamlı düzeyde azaldığı saptandı.

TARTIŞMA: Kalsiyum dobesilat, antioksidan ve antienflamatuvar etkileriyle ilişkili olarak önemli bir hepatoprotektif etki göstermiştir.

Anahtar sözcükler: Deneysel; histopatoloji; iskemi reperfüzyon; kalsiyum dobesilat; karaciğer, oksidatif stres.

Ulus Travma Acil Cerrahi Derg 2018;24(5):391-397

doi: 10.5505/tjtes.2018.33238

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

397

EXPERIMENTAL STUDY

Role of pentoxifylline and iloprost in the prevention of ischemia-reperfusion injury in an experimental model of intestine ischemia-reperfusion in rats Uğur Abakay, M.D.,1 Sinan Soylu, M.D.,1 Sabahattin Göksel, M.D.,2 Bülent Saraç, M.D.,3 Zeynep Deniz Şahin İnan, M.D.,4 Erol Çakmak, M.D.,5 Özge Korkmaz, M.D.,2 Atilla Kurt, M.D.,1 Hüsnü Çağrı Genç, M.D.1 1

Department of General Surgery, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

2

Department of Cardiovasculer Surgery, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

3

Department of Pharmacology, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

4

Department of Histology, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

5

Department of Gastroenterolgy, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

ABSTRACT BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury can lead to multiple organ failure and death. The aim of this study was to investigate the effects of pentoxifylline and iloprost administered before reperfusion in intestinal ischemia.

METHODS: In total, 25 male Wistar Albino rats weighing 250–300 g were divided into five groups each comprising five subjects: control group (n=5), sham group (n=5, no I/R), I/R group (n=5, 45 min ischemia, and 120 min reperfusion), I/R + pentoxifylline group (n=5, 45 min ischemia following intraperitoneal 50 mg/kg pentoxifylline and 120 min reperfusion), and I/R + iloprast group (n=5, 45 min ischemia followed by intraperitoneal 2 mcg /kg iloprost and 120 min reperfusion). At the end of the experiment, ileum specimens were stained using hematoxylin-eosin and histopathologically evaluated using the Chiu score. Isometric contraction–relaxation responses were recorded using organ baths for contraction–relaxation responses.

RESULTS: Pentoxifylline provided a significant improvement in response to histopathological and contraction–relaxation responses.

Although iloprost provided recovery in reperfusion injury, it was not statistically significant.

CONCLUSION: Our findings demonstrate that pentoxifylline may be promising in preventing small bowel ischemia-reperfusion injury. We concluded that further clinical and experimental studies for iloprost are needed.

Keywords: Acute mesenteric ischemia; iloprost; ischemia-reperfusion injury; pentoxifylline.

INTRODUCTION Acute mesenteric ischemia (AMI) is a fatal vascular pathology with mortality ranging from 50% to 80%.[1] Small intestinal ischemia occurs due to intravascular reasons such as arterial thrombosis, embolism, Henoch-Schonlein purpura, disseminated intravascular coagulation or external pressure on vessels, including volvulus, invagination, incarcerated inguinal

hernia, tumor and fibrotic band.[2] Delayed diagnosis, comorbidities, and ischemia-reperfusion (I/R) are associated with poor prognosis.[3] Long periods of ischemia result in cellular damage and death. Reperfusion leads to the release of free oxygen radicals that accelerate tissues deteriotion This is known as reperfusion injury.[1] Therefore, it is critical reduce

Cite this article as: Abakay U, Soylu S, Göksel S, Saraç B, Şahin İnan ZD, Çakmak E, et al. Role of pentoxifylline and iloprost in the prevention of ischemia-reperfusion injury in an experimental model of intestine ischemia-reperfusion in rats. Ulus Travma Acil Cerrahi Derg 2018;24:398-404.

Address for correspondence: Sinan Soylu, M.D. Cumhuriyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 58140 Sivas, Turkey Tel: +90 346 - 219 11 56 E-mail: soylu.sinan@hotmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):398-404 DOI: 10.5505/tjtes.2018.22227 Submitted: 04.01.2018 Accepted: 12.03.2018 Online: 28.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

398

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Abakay et al. The effects of iloprost and pentoxifylline on ischemia - reperfusion injury

the duration of ischemia with early diagnosis and appropriate treatment methods and reduce the damage that occurs during the reperfusion period to minimum.[4,5]

traperitoneally (Ilomedin®, 20 μg/mL, Bayer Schering Pharma; Bayer Turk Kimya San. Ltd. Sti, Umraniye, Istanbul, Turkey) (I/R + ILP). No death was observed during the study.

Both pentoxifylline (PTX) and iloprost have been used in peripheral vascular diseases for many years, and the results are satisfactory.[4,5]

Rats were anesthetized by subcutaneous injection of ketamine (90 mg/kg; Ketalar®; Parke-Davis, Istanbul, Turkey) and xylazine (3 mg/kg Rompun®; Bayer, Istanbul, Turkey). After anesthesia was induced, laparotomy was performed with an abdominal midline incision. The intestines were moved to the body surface, and the superior mesenteric artery (SMA) was dissected after cutting the Treitz ligament. Following laparotomy, ileum resection was performed in the control group. The rats in the sham group were monitored until the end of the experiment after the demonstration of SMA. A 45-min ischemia was established with the compression of the SMA from the exit site of the aorta by an atraumatic microvascular clamp in the I/R groups. Adequate occlusion was confirmed by the absence of pulsation in the mesenteric vessels and paleness. The clamp was removed at the end of 45 min and reperfusion was provided for 120 min. During the waiting periods, the abdomen was closed using wet and sterile tampons. Ileum resection was performed for pathological examination and isometric contraction responses in the test animals. At the end of the study, the rats were euthanized using a high dose of pentothal sodium.

PTX has varying effects on providing cell membrane fluidity, immunomodulation, stimulation of fibrinolysis, anticoagulation, and fibroblast physiology.[4,6] Some studies have shown that PTX therapy reduces cardiac output, improves liver perfusion and intestinal blood flow after bleeding and post-resuscitation, and has an important effect in improving ischemic conditions in colon anastomoses.[7–9] Additionally, it has been reported to reduce oxidative stress and inflammatory indices by suppressing the production of tumor necrosis factor-α and interleukins (IL-1, IL-6, and IL-10).[10] Iloprost is frequently used in the treatment of diabetic foot, pulmonary arterial hypertension and peripheral vascular disease, such as Burger’s disease.[11] It is a potent vasodilator and a member of the prostacyclin analog group, which has antiplatelet, anti-proliferative and anti-inflammatory properties.

It can alter the endothelial prostaglandine I2/ thromboxane A2 (PGI2/TXA2) ratio in favor of prostacyclin.[12] Iloprost is currently being used in patients with peripheral vascular disease, especially those with chronic ischemic chest pain. It acts by increasing nitric oxide synthase in the vascular tissue. It is believed that this pathway may be effective in I/R injury in the intestine.[13] Therefore, iloprost application was planned in this study.

In this study, we aimed to evaluate the effects of PTX and iloprost in an I/R model of the mesenteric artery of rats. We evaluated the contraction - relaxation responses and pathological specimens in the small intestine segments.

The tissues of ileum were fixed at 10% buffered formaldehyde, and sections with a thickness of 5 μm were obtained.

The sections were, then, stained using Hematoxylin & Eosin and were examined under a light microscope (Olympus BX51 Tokyo, Japan). Histopathological evaluations of the intestinal sections were performed according to the scoring system defined by Chiu et al. and the mucosal lesions were graded between 0 and 5 (Table 1).[14] Resected ileum segments were placed into Krebs bicarbonate solution. Then, they were incubated at 4°C for 4 h. This Table 1. Chiu scoring system[14]

MATERIALS AND METHODS

Grade

Characteristics

This experimental study was conducted between September 2016–November 2016 in the Cumhuriyet University experimental animal laboratory. The study protocol was approved by the Local Ethics Committee (Date/number: 04,08,2016/050-04-04-78).

0

Mucosa with normal villi

1

Development of the sub-epithelial Gruenhagen’s space,

usually at the villus apex, frequently associated with

capillary congestion

2

Extension of the sub-epithelial space with moderate

A total of 25 Wistar Albino male rats weighing 250–300 g were used in this study. The rats were kept in wire cages in a 12 h light/dark cycle at room temperature and fed with standard rat diet and water. They were allowed to drink only water for 12 h before surgery. The rats were, then, randomly divided into five groups as follows: control, sham, I/R, I/R treated with 50 mg/kg PTX administered intraperitoneally (Trental®; Sanofi Aventis Pharma, Istanbul, Turkey) (I/R + PXT) and I/R treated with 20 μg/mL iloprost administered in-

lifting of the epithelial layer from the lamina propria

3

Massive epithelial lifting down the sides of the villi

4

Denuded villi with lamina propria and dilated

capillaries exposed

Increased cellularity of lamina propria may be noted

5

Digestion and disintegration of lamina propria;

hemorrhage and ulceration

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

399

Abakay et al. The effects of iloprost and pentoxifylline on ischemia - reperfusion injury

Table 2. Emax and pD2 values of contraction responses to histamine, carbachol and substance p of tissues Grups

Contraction to histamine

Contraction to carbachol

Contraction to substance p

Control Emax pD2

120.62±8.13 141.57±5.99 84.44±6.13 6.31±0.35 6.36±0.29 6.34±0.33

Sham Emax pD2

117.67±6.16 128.69±7.10 77.98±6.02 6.37±0.27 6.25±0.30 6.31±0.29

Ischemia/Reperfusion Emax 35.65±6.02+ 45.75±7.03+ 24.22±7.30+ pD2

6.22±0.31 6.41±0.31 6.40±0.29

Pentoxifylline + Ischemia/Reperfusion Emax 81.00±5.93* 91.09±5.98* 56.65±6.01* pD2

6.25±0.26 6.33±0.28 6.30±0.31

Iloprost + Ischemia/Reperfusion Emax 41.98±5.72+ 49.87±6.50+ 29.12±6.03+ pD2

6.41±0.32 6.36±0.29 6.28±0.34

*Significantly lower than control and sham operation groups, significantly higher than ischemia reperfusion and iloprost + ischemia reperfusion groups (p<0.05). +Significantly lower than control, sham and PTX + ischemia reperfusion groups (p<0.05).

procedure was done to equilibrate the contractions and stabilize the subsequent contractile responses to carbachol and substance p. Thereafter, the ileum segments were placed into the Krebs bicarbonate solution specific for the ileum, with a temperature set at 37°C and aerated with 95% O2 and 5% CO2, to determine the spontaneous contraction responses (amplitude and frequency) for each group (content: as mmol/L; sodium chloride, 120; potassium chloride, 4.6; calcium chloride, 2.5; magnesium chloride, 1.2; sodium bicarbonate, 22; sodium phosphate monobasic and glucose, 11.5).

The ileal segments were connected to the transducer (Grass FT 03, Quincy Mass., USA) and recorded using a polygraph (Grass 79 E, Quincy Mass., USA) to measure isometric contractions.

Contraction was initially achieved through the administration of 80 mmol/L KCl, and contraction responses to histamine (10-9–10-4 mol/ L), carbachol (10-9–10-4 mol/L) and substance p (10-9–10-4 mol/L) were examined to see receptor-mediated responses of tissues, and these contraction responses were expressed as percentages (%) of contractions with KCl. The maximal contraction responses (Emax) of the tissues and the negative logarithm values of half of the maximal contraction concentration (pD2) were calculated (Table 2).

Statistical Analysis Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS), version 16.0, software (SPSS Inc., Chicago, IL, USA). Descriptive data were expressed as mean + standard error of the mean. Analysis of variance was 400

used for the initial analysis, and the Newman Keuls test was used as the post-hoc test. A p value of <0.05 was considered statistically significant.

RESULTS In the histopathological evaluation, a usual appearance of the villi was observed in the tunica mucosa layer in the sham group. The epithelium surrounding the villi was regular and the lamina propria of the tunica mucosa was appropriately positioned. In the I/R group, the loss of villi and occasional dilated capillaries with the disruption of the integrity of lamina propria were observed. In the IL group, in addition to loss of villi and disruption of integrity of lamina propria, intensive bleeding sites and inflammatory cells were observed.

Compared to the I/R group, although there were more bleeding sites in the lamina propria, the villi were not completely ruptured and the lamina propria on the base of the villi was regular. In the PTX group, occasional loss of villi and regular lamina propria layer were observed. Also, compared to the iloprost groups, less epithelial loss, more regular lamina propria and villus structure was observed (Fig. 1).

When Chiu scores of the groups were compared; the lowest score was in the control group and then in the sham, PTX, iloprost groups, respectively, and the highest in the I/R group.

In the PTX group, the Chiu score was significantly higher than the control and sham groups (p=0.023 ), and was significantly lower than the I/R and iloprost groups (p=0.005, p=0.004; Fig. 2).

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Abakay et al. The effects of iloprost and pentoxifylline on ischemia - reperfusion injury

taneous contractions in both amplitude and frequency in the I/R group were significantly decreased, compared to the control and sham groups (p<0.05). Spontaneous contraction responses were significantly improved in the I/R group, compared to I/R alone (p<0.05; Fig. 3).

(b)

(c)

(d)

Figure 1. Histopathological images of biopsy samples obtained from the ileum (×40, hematoxylin-eosin). (a) Sham group (40X): Intestinal layers with 0 -1 degrees of injury are shown. Normal-looking villus is observed in the tunica mucosa layer. The epithelium that surrounds the villi was regular and lamina propria of the tunica mucosa was in an appropriate location. (b) I/R group (40X): The villi with 2 -5 degrees of injury are shown with great magnification.

Intensive cell loss in epithelial cells of villus, dense blood vessels in lamina propria are seen. (c) Iloprost group (40X): The villi with 2 -3 degrees of injury are shown with great magnification. The loosing of the villi surrounding the epithelium and the intense dilated blood vessels in the lamina propria are seen. (d) PTX group (40X): The intestinal layers with 1 -2 degrees of injury are shown. Loss of villi and regular lamina propria layer are seen.

There was no significant difference between the groups in terms of response to 80 mmol/L KCl (p>0.05). The highest contraction responses in terms of receptor-mediated responses were in the tissues of the control group. In the tissues of I/R group, the receptor-mediated responses had least contractions for all three drugs (histamine, carbachol and substance – p). The contraction responses obtained from the I/R group treated with iloprost were similar to those of the I/R alone group (p>0.05). Although the response of tissues treated with PTX was not satisfactorycompared to the control and sham groups for all three drugs, it was significantly higher than the groups treated with iloprost and I/R alone (p<0.05; Fig. 4).

The Emax and pD2 values of the contraction responses of the three drugs in the five groups are shown in Table 2.

Histamine (% KCI)

(a)

150

Control

125

Sham

100

I/R

75

Pentoxifylline+I/R

50

Iloprost+I/R

25 0 10-8

5.00

10-7 10-6 10-5 Concentration [M]

10-4

10-7 10-6 10-5 Concentration [M]

10-4

10-7 10-6 10-5 Concentration [M]

10-4

150 125 Carbachol (% KCI)

5.00

75 50 0 10-8

5.00 0

100

25

5.00

150 Control

Sham

I/R

Pentoxifylline Iloprost +I/R +I/R

Figure 2. Mean scores of groups according to Chiu scoring. There is a statistically significant difference of the control and sham groups among other groups (p<0.005). There is a statistically significant difference between PTX + I/R group and I/R and iloprost + I/R groups (p<0.005). There is no significant difference between the I/R and iloprost I/R groups (p>0.05).

When responses of the groups were examined: The spontaneous contractions in both amplitude and frequency of the control group were observed to be the highest. Although spontaneous contraction responses in the sham group were slightly less than those in the control group, there was no significant difference between two groups (p>0.05). SponUlus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Substance P (% KCI)

Mean scores of groups

5.00

125 100 75 50 25 0 10-8

Figure 3. Amplitude and frequencies of spontaneous contractions. *Significantly lower than the control and sham operation groups (p<0.05). αSignificantly lower than the control and sham operation groups, and significantly higher than ischemia reperfusion and iloprost + I/R groups (p<0.05). βSignificantly lower than the control and sham operation groups (p<0.05).

401

Abakay et al. The effects of iloprost and pentoxifylline on ischemia - reperfusion injury

Amplitudes (% KCI)

100 80

Control Sham I/R Pentoxifylline+I/R Iloprost+I/R

a

60 40

b

*

20

Frequency (Num./10 Min)

0 80 60 a 40

b

* 20

Iloprost+I/R

Pentoxifylline+I/R

I/R

Sham

Control

0

Figure 4. Contraction responses of tissues to histamine, carbachol and substance -p (% of KCl contractions). *Significantly lower than the control and sham operation groups, significantly higher than I/R and iloprost + I/R groups (p<0.05). +Significantly lower than control, sham operation and PTX + ischemia reperfusion groups (p<0.05).

DISCUSSION The first finding of our study was that PTX reduced the histopathological damage and improved contraction -relaxation responses in the ileum segments in the intestinal I/R injury, but the same effects were not observed with iloprost treatment.

AMI is a clinical condition that may progress to multi-organ failure and is associated with high mortality and morbidity rates following acute vascular insufficiency.[15] An ischemia lasting less than 20 min in the small intestines does not significantly change the mucosa, while an ischemia lasting longer than 2 h may cause permanent damage and even transmural necrosis.[16] Intestinal ischemia and reperfusion lead to the formation of inflammatory cytokines and free oxygen radicals.

[17] Cytotoxic events cause toxic products to cross the systemic circulation by impairing the barrier function of the gut, and result in multi-organ failure by affecting the kidneys, liver, and heart and, the regional tissues and lung particularly.[18] PTX inhibits the enzyme phosphodiesterase. It exerts its therapeutic effects by increasing the blood flow and tissue oxygenation.[19] Although it leads to an increase in primary cardiac output and a decrease in the total systemic vascular resistance with systemic vasodilatation, it does not lead to a significant change in the systemic arterial pressure. In addi402

tion, it results in a decrease in the resistance to blood flow by increasing erythrocyte flexibility which decreases the total blood viscosity.[14] Also, it has been reported that PTX inhibits the production of pro-inflammatory cytokines and has anti-inflammatory features and protects the mitochondrial structures of the cells.[20] Therefore, it is widely used in the medical treatment of peripheral arterial diseases.[4,5,10] Prostaglandins are biologically active mediators released from endothelial cells, smooth muscles, pericytes, fibroblasts, mast cells, leukocytes, and platelets. They have vasoactive functions that are thought to be important in an I/R injury. PGI2 is an unstable metabolite that increases cyclic-adenosine monophosphate concentration in the vascular smooth muscle,[21] inhibits platelet aggregation, and leads to vasodilatation.[22] Iloprost is a stable PGI2 analog and is widely used in the treatment of pathologies such as diabetic foot, peripheral arterial disease, venous ulcers and Raynaud’s phenomenon.

[5] We aimed to compare the consequences of PTX and ilioprost on mesenteric ischemia due to these effects.

Different models were formed to generate experimental I/R injury. In a study, Mallick et al.[23] generated experimental models by performing 30 min of ischemia and 120 min of reperfusion, while Arruda et al.[24] determined their injury model as 45 min of ischemia and 120 min of reperfusion. In our study, we performed 45 min of ischemia and 120 min of reperfusion. We achieved an effective existing I/R model.

In our study, 50 mg/kg PTX and 1 µg/kg iloprost were administered intraperitoneally to the experimental groups during the period of reperfusion for 120 min after 45 min of ischemia, and ileum resection was performed. In a similar study conducted by Savaş et al.,[25] PTX was administered intraperitoneally at a dose of 50 mg/kg before 15 min of ischemia induction. They found that the injury was significantly reduced in the PTX group, compared to the control group. However, they found that PTX reduced mucosal injury, but did not normalize. In our study, PTX was given during the reperfusion phase, which is more realistic in practice. Because of patients with AMI were usually admit with in ischemic phase and during the treatment period was provided reperfusion.

Our results demonstrated that PTX treatment reduced I/R injury. Histopathological results and contraction -relaxation responses were improved in this treatment. These results were statistically significant and, consistent with literature.

In literature several iloprost studies have shown that antiinflammatory parameters decreased in the I/R injury condition.[26–28] In our study, we did not evaluate the measured anti-inflammatory parameters but histopatological results and contraction relaxation responses of the intestinal tissues were observed in the iloprost group. Although the results were better than the I/R group, it was not statistically significant.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Abakay et al. The effects of iloprost and pentoxifylline on ischemia - reperfusion injury

Limitations There were some limitations in this study. Evaluation of the superoxygen radicals and total anti-oxidant capacity which are effective I/R injury, could give clearer results. These parameters could not be measured because the laboratory conditions were not suitable. Futures studies in this regard are needed.

Conclusions Our study is the first study to investigate the effects of administration of PTX and iloprost on the injury after I/R by comparing the histology and contraction-relaxation responses. Elderly patients with widespread atherosclerosis, diabetes, atrial fibrillation and many other risk factors are at risk for mesenteric artery embolism or thromboembolism.

In this group of patients, with the establishment of diagnosis, giving PTX may recover the remaining intestinal tissue with less injury from reperfusion. The same effects may not be provided with iloprost. However, there is a need for more detailed experimental studies on this subject.

Funding: None Acknowledgements: The authors declare that this study has received no financial support.

Conflict of interest: None declared.

REFERENCES 1. Berland T, Oldenburg WA. Acute mesenteric ischemia. Curr Gastroenterol Rep 2008;10:341–6.

2. Polat H, Türk Ö, Yaşar B, Uysal O. The effect of ligustrazin in intestinal ischemia reperfusion injury generated on rats [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2015;21:163–7.

3. Cotran, RS, Kumar V, Robbins SL, Lesão e morte celular. In: Robbins, editor. Patologia estrutural e funcional. 5th ed. Rio de Janeiro: Guanabara Koogan; 1996. p. 1–30.

4. Paradowski, PT, Zeman, K. Pentoxifylline [Article in Polish]. Post Hig Med Doswiad 1995;49:201–20.

5. Altstaedt HO, Berzewski B, Breddin HK, Brockhaus W, Bruhn HD, Cachovan M, et al. Treatment of patients with peripheral arterial occlusive disease Fontaine stage IV with intravenous iloprost and PGE1: a randomized open controlled study. Prostaglandins Leukot Essent Fatty Acids 1993;49:573–8.

6. Müller R. Hemorheology and peripheral vascular diseases: a new therapeutic approach. J Med 1981;12:209–36.

7. Ribeiro EA, Poli-de-Figueiredo LF, Vincenzi R, Galvao FH, Margarido N, Rocha-E-Silva M, et al. Intraportal versus Systemic Pentoxifylline Infusion after Normothermic Liver Ischemia: Effects on Regional Blood Flow Redistribution and Hepatic Ischemia-Reperfusion Injury. HPB Surg 2013;2013:689835.

8. Cruz RJ Jr, Yada-Langui MM, de Figueiredo LF, Sinosaki S, Rocha e Silva M. The synergistic effects of pentoxifylline on systemic and regional perfusion after hemorrhage and hypertonic resuscitation. Anesth Analg.

2006;102:1518–24.

9. Luo M, Dong L, Li J, Wang Y, Shang B. Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats. Int J Clin Exp Pathol 2015;8:8990–6.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

10. Oliveira TRR, Oliveira GF, Simões RS, Tikazawa EH, Monteiro HP, Fagundes DJ, et al. The role of ischemic preconditioning and pentoxifylline in intestinal ischemia/reperfusion injury of rats. Acta Cir Bras 2017;32:559–67.

11. Senol S, Senol A. Investigation of Asymmetric and Symmetric Dimethylarginine Levels after Iloprost Treatment in Patients with Buerger’s Disease. Eur J Vasc Endovasc Surg 2017;53:439–42.

12. Gomberg-Maitland, M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. European Respir J 2008;31:891–901.

13. Mısırlıoğlu G, Hüseyin S, Yüksel V, Güçlü O, Karadağ H, Canbaz S, et al. In vitro effects of prostaglandin E1, prostaglandin I2 and papaverine on internal thoracic artery graft [Article in Turkish]. Turk Gogus Kalp Dama 2015;23:463–6.

14. Ehrly AM. The effect of pentoxifylline on the deformability of erythrocytes and on the muscular oxygen pressure in patients with chronic arterial disease. J Med 1979;10:331–8.

15. Aguilar-Nascimento JE, Salomão AB, Nochi RJ Jr, Nascimento M, Neves Jde S. Intraluminal injection of short chain fatty acids diminishes intestinal mucosa injury in experimental ischemia-reperfusion. Acta Cir Bras 2006;21:21–5.

16. Park PO, Haglund U, Bulkley GB, Fält K. The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion.

Surgery 1990;107:574–80.

17. Clark ET, Gewertz BL. Intermitant ischemia potentiates intestinal reperfusion injury. J Vasc Surg 1991;13:601–6.

18. Köksoy C, Kuzu MA, Kuzu I, Ergün H, Gürhan I. Role of tumour necrosis factor in lung injury caused by intestinal ischaemia-reperfusion. Br J Surg 2001;88:464–8.

19. Foster ME, Laycock JR, Silver IA, Leaper DJ. Hypovolaemia and healing in colonic anastomoses. Br J Surg 1985;72:831–4.

20. Gómez-Cambronero L, Camps B, de La Asunción JG, Cerdá M, Pellín A, Pallardó FV, et al. Pentoxifylline ameliorates cerulein-induced pancreatitis in rats: role of glutathione and nitric oxide. J Pharmacol Exp Ther 2000;293:670–6.

21. Kadowitz PJ, Chapnick BM, Feigen LP, Hyman AL, Nelson PK, Spannhake EW. Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2. J Appl Physiol Respir Environ Exerc Physiol 1978;45:408–13.

22. Mulvin D, Jones K, Howard R, Grosso M, Repine J, Johnston M. The effect of prostacyclin as a constituent of a preservation solution in protecting lungs from ischemic injury because of its vasodilatory properties.

Transplantation 1990;49:828–30.

23. Mallick IH, Yang W, Winslet MC, Seifalian AM. Ischemia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 2004;49:1359–77.

24. de Arruda MJ, Poggetti RS, Fontes B, Younes RN, Souza AL Jr, Birolini D. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats. Clinics (Sao Paulo) 2006;61:21–8.

25. Savaş C, Aras T, Cakmak M, Bilgehan A, Ataoğlu O, Türközkan N, et al.

Pentoxifylline inhibits overflow and reduces intestinal reperfusion injury.

J Pediatr Surg 1997;32:905–10.

26. Wei W, Wei FC, Hung LM. Diazoxide ameliorates microcirculatory disturbances through PKC-dependent pathway in I/R-injured rat cremaster muscles. J Biomed Sci 2005;12:521–9.

27. Katırcıoğlu SF, Saritaş Z, Ulus AT, Yamak B, Yücel D, Ayaz S. Iloprost added to the cardioplegic solutions improves myocardial performance.

Prostaglandins Other Lipid Mediat 1998;55:51–65.

28. Hasturk A, Atalay B, Calisaneller T, Ozdemir O, Oruckaptan H, Altinors N. Analysis of serum pro-inflammatory cytokine levels after rat spinal cord ischemia/reperfusion injury and correlation with tissue damage. Turk Neurosurg 2009;19:353–9.

403

Abakay et al. The effects of iloprost and pentoxifylline on ischemia - reperfusion injury

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçanlarda bağırsak iskemi-reperfüzyonunun deneysel modelinde iskemi-reperfüzyon hasarının önlenmesinde pentoksifilin ve iloprostun rolü Dr. Ugur Abakay,1 Dr. Sinan Soylu,1 Dr. Sabahattin Göksel,2 Dr. Bülent Saraç,3 Dr. Zeynep Deniz Şahin İnan,4 Dr. Erol Çakmak,5 Dr. Özge Korkmaz,2 Dr. Atilla Kurt,1 Dr. Hüsnü Çağrı Genç1 Cumhuriyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Sivas Cumhuriyet Üniversitesi Tıp Fakültesi, Kalp Damar Cerrahisi Anabilim Dalı, Sivas Cumhuriyet Üniversitesi Tıp Fakültesi, Farmakoloji Anabilim Dalı, Sivas 4 Cumhuriyet Üniversitesi Tıp Fakültesi, Histoloji Anabilim Dalı, Sivas 5 Cumhuriyet Üniversitesi Tıp Fakültesi, Gastroenteroloji Anabilim Dalı, Sivas 1 2 3

AMAÇ: İntestinal iskemi-reperfüzyon (IIR) hasarı çoklu organ yetersizliği ve ölüme yol açabilir. Bu çalışmanın amacı, intestinal iskemide reperfüzyon öncesi uygulanan pentoksifilin ve iloprostun etkilerini araştırmaktır.

GEREÇ VE YÖNTEM: 25–300 gr agırlığında 25 Wistar-Albino cinsi sıçan, her bir grupta beş sıçan olacak şekilde beş gruba ayrıldı: Kontrol grubu (n=5), sham grubu (n=5 IR yok), IR grubu (n=5, 45 dk iskemi 120 dk reperfüzyon), IR+Ptx grubu (n=5, 45 dk iskemiyi takiben 50 mg/kg intraperitoneal pentoksifilin ve 120 dk reperfüzyon), IR+IL (n=5, 45 dk iskemiyi takiben 2 mcg/kg intraperitoneal iloprost ve 120 dk reperfüzyon). Deney sonunda ileum örnekleri hemotoksilen-eosin ile boyandı ve histopatolojik olarak Chiu skorlamasına göre değerlendirildi. Izometrik kasılma –gevşeme cevapları organ banyosu kullanılarak kaydedildi.

BULGULAR: Pentoksifilin histopatoljik ve kasılma –gevşeme cevapları açısından anlamlı düzelme sağladı. İloprost reperfüzyon hasarını düzeltmesine rağmen bu düzelme istatistiksel olarak anlamlı değildi.

TARTIŞMA: Bulgularımıza göre pentoksifilin incebağırsak iskemi-reperfüzyon hasarından korumada ümit verici olabilir. Öte yandan, iloprost için daha ileri klinik ve deneysel çalışmalara gereksinim duyulmaktadır.

Anahtar sözcükler: Akut mezenterik iskemi; iloprost; iskemi reperfüzyon hasarı; pentoksifilin.

Ulus Travma Acil Cerrahi Derg 2018;24(5):398-404

404

doi: 10.5505/tjtes.2018.22227

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

EXPERIMENTAL STUDY

Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis Yüksel Altınel, M.D.,1 Soon Soup Chung, M.D.,2 Güven Okay, M.D.,3 Ahmet Fatih Işık, M.D.,5 Ersin Öztürk,1 Halil Özgüç, M.D.1 1

Department of General Surgery, Uludağ University Faculty of Medicine, Bursa-Turkey

2

Department of General Surgery, Ewha University Medical Faculty, Seoul-Korea

3

Department of Biostatistics, Uludağ University Faculty of Medicine, Bursa-Turkey

4

Department of Pathology, Uludağ University Hospital, Bursa-Turkey

5

Department of Textile, Uludağ University Faculty of Textile Engineering, Bursa-Turkey

Nesrin Uğraş, M.D.,4

ABSTRACT BACKGROUND: We evaluated the feasibility of chitosan-coated sutures for intestinal anastomosis strength through wound-healing effect.

METHODS: Vicryl and PDS sutures were coated with 2% chitosan. While laparotomy was applied to the first group, chitosan was applied in the peritoneal cavity in the second group. Then the following materials were applied to colon anastomosis, in order: Vicryl, PDS, chitosan-coated Vicryl, and chitosan-coated PDS sutures. On the 7th and 14th days, eight rats from each group were euthanized.

RESULTS: The adhesion scores of chitosan and control groups were lower than the suture groups. The vascularization of Vicryl–chitosan was lower than PDS–chitosan on the 14th day (p=0.038). Fibroblast cells and vascularization of anastomosis with chitosan-coated Vicryl were lower than Vicryl and chitosan-coated PDS on the 14th day (p<0.05). The tensile strength of Vicryl–chitosan increased more than Vicryl in vitro (p<0.05) on the 14th and 7th days, but there was no difference in vivo. The tensile strength of PDS–chitosan decreased more than PDS on the 7th day in vivo (p<0.05).

CONCLUSION: The chitosan-coating effect on the adhesion and reinforcement of anastomosis in some parts of Vicryl in vitro and PDS in vivo was slightly improved.

Keywords: Anastomosis; chitosan; PDS suture; tensile strength; Vicryl suture; wound healing.

INTRODUCTION Leakage from colonic anastomosis is caused by multiple factors and results in morbidity and mortality.[1] Anastomotic leakage following colorectal resections occurs in 3%–23% of cases.[2] For various reasons, this anastomotic dehiscence is a major problem for anastomotic healing. To reduce this complication, reinforcement of the anastomosis by biological or artificial materials has been tried. Of primary importance are the types of suture materials used for the primary closure of tissues separated by surgical procedures. Numerous sutures with different mechanical properties are used in surgical pro-

cedures, which lead to tensile loading. There has been little research on the changes in the mechanical properties of surgical sutures in experimental conditions.[3,4] Peritoneal adhesion formation resulting from tissue ischemia, inflammation, fibrin organization, and collagen formation following abdominal surgeries remains a major problem.[5,6] From various agents that have been used to reduce each of these steps,[5,6] we aimed to investigate chitosan for intra-abdominal inflammatory processes, including adhesion formation and anastomosis strength.

Cite this article as: Altınel Y, Chung SS, Okay G, Uğraş N, Işık AF, Öztürk E, et al. Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis. Ulus Travma Acil Cerrahi Derg 2018;24:405-411.

Address for correspondence: Yüksel Altınel, M.D. Harvard Medical School Boston, United States Tel: +18622834536 E-mail: yuksel_altinel@hms.harvard.edu Ulus Travma Acil Cerrahi Derg 2018;24(5):405-411 DOI: 10.5505/tjtes.2018.59280 Submitted: 30.11.2017 Accepted: 11.03.2018 Online: 10.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

405

Altınel et al. Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis

The alkaline deacetylation of chitin obtained from the exoskeleton of crustaceans generates a natural polymer called chitosan. Immunological, antibacterial, wound-healing activity, biodegradability, and hemostatic potential are among the biological properties affected by chitosan.[7,8] We hypothesized that the use of chitosan to suture materials could decrease the dehiscence of colon anastomosis, leakage, and adhesion by preventing inflammation.

Using the multifilament suture VicrylTM (Ethicon, Somerville NJ) and the monofilament suture PDSTM (Ethicon, Somerville NJ), we compared the effectiveness of chitosan-coated sutures with that of non-chitosan-coated sutures in vivo and in vitro. Furthermore, this study measured the effect of chitosan on the tensile strength of different sutures. In this experimental model, we also investigated the effect of chitosan coating on adhesion formation and inflammatory responses.

MATERIALS AND METHODS This study was approved by the Medical Faculty of Uludag University, Experimental Animals Production and Research Laboratory Ethical Committee (2010/05/02). The protocols were in compliance with the Declaration of Helsinki.

Ninety-six adult female Wistar albino rats (aged 3 or 4 months, weighing between 250 and 300 g) were used. The animals were kept in standard rat cages, with a maximum of four animals per cage, under standard laboratory conditions with pellet food, specifically manufactured for rats and water supplied using a drinking bottle. They were housed at a temperature of 20°C–22°C, with a relative humidity of 50%–60% and 12-h light–dark cycles. Rats were randomly put into six groups, of 16 rats each, and were further divided into groups of eight rats for evaluation on the 7th and 14th days to compare outcomes.

Experimental Groups Group 1: The control group; only laparotomy was performed on 16 rats. Then, eight rats from each group were sacrificed on the 7th and 14th days.

Group 2: The chitosan group; only 100 mg of chitosan powder was applied into the peritoneal cavity over the distal part of the cecum following dry gauze repeatedly rubbed to cause sub-serosal bleeding in 16 rats. Then, eight rats from each group were sacrificed on the 7th and 14th days.

Group 3: The Vicryl suture was used to perform a colon anastomosis after cecal enterotomy on 16 rats. Then, eight rats from each group were sacrificed on the 7th and 14th days.

Group 4: The 5/0 PDS suture was used to perform a colon anastomosis after cecal enterotomy on 16 rats. After that eight rats for each group were sacrificed on the 7th and 14th days.

406

Group 5: The chitosan-coated 5/0 Vicryl sutures were used to perform a colon anastomosis after cecal enterotomy on 16 rats. Then, eight rats from each group were sacrificed on the 7th and 14th days.

Group 6: The chitosan-coated 5/0 PDS sutures were used to perform a colon anastomosis after cecal enterotomy on 16 rats. Then, eight rats from each group were sacrificed on the 7th and 14th days.

The Chitosan-Coating Procedure The chitosan (Sigma, MO, USA) powder was added to a 1% (1 ml acetic acid, 99 ml water) acetic acid (100%, Merck, Germany) solution to prepare a 2% (2 g chitosan, 98 g acetic acid solution) chitosan solution. Then, 5/0 PDS and 5/0 Vicryl sutures were placed into the 2% chitosan solution and incubated for 30 min. The sutures were then warmed at 30°C in an oven in a textile engineering laboratory. Sterilization of the sutures was performed later.

Surgical Procedures All animals were fasted overnight before surgery. Anesthesia was maintained with an injection of 10 mg/kg intramuscular ketamine (Ketalar, Phizer, AUSTR) and 1 mL/kg xylazine (Rompun, Bayer, Germany).

An 8-cm midline incision was made on the abdomen after antisepsis by povidone iodine application. Segments of colon approximately 2 cm distal to the cecum were identified and partially transected, following which continuity was restored by anastomosis using a single layer of continuous 5/0 Vicryl or 5/0 PDS sutures.

Moreover, we only performed laparotomy in the control group. The laparotomy closure was performed via a continuous suture technique using 000 polypropylene (Prolene, Ethicon Inc., Somerville, NJ, USA). The skin was closed using a surgical stapler.

On the 7th postoperative day, eight randomly chosen rats from each group were sacrificed by cervical dislocation. The others were sacrificed on the 14th day. Through the initial laparotomy scar, the abdomen was opened in a cranialto-caudal manner by midline incision in order to view the exact intra-abdominal adhesion formations. In the suture groups, anastomotic segments, including the anastomosis in the middle surrounding colon tissue, and adhesions of approximately 6×3 cm were carefully resected. In the chitosan group, the damaged cecum area was excised. The specimens were washed in saline, and stool was removed from the lumen. The anastomotic tissue around sutures a 4×3 cm wide strips was taken for the tensile strength of sutures, and a 2×1 cm tissue of anastomosis was taken for histopathological evaluation.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Altınel et al. Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis

Table 1. Adhesion grading according to Diamond classification Score Extent

Tenacity

0 0%

Type

None

<25%

2

25–50%

Lysed with traction

Opaque, no vessels

3

50–75%

Required sharp dissection

Opaque, small vessels

4

Easily lysed

None

1

Filmy, no vessels

>75%

Table 2. Histologic grading scale for inflammatory cell infiltration, blood vessel and fibroblast ingrowth and collagen deposition 0

No evidence

1

Occasional evidence

2

Light scattering

3

Abundant evidence

4

Confluent cells or fibers

Opaque, large vessels

Statistical Analysis The adhesion, tensile strength, and histopathological scores were compared with Kruskal–Wallis test and Mann–Whitney U-test for intergroup comparisons to evaluate the data. The results were showed as median (minimum–maximum). SPSS 23.0 software (Chicago, IL, USA) was used. A p value <0.05 on a 2-tailed test was considered statistically significant.

RESULTS

The adhesions were graded according to the Diamond classification by a general surgeon who had no knowledge about each rat’s groups (Table 1).[9]

One rat each from Vicryl and Vicryl–chitosan-coated groups and two from PDS group died after the intervention for unidentified reasons. Throughout the investigation, no infections or anastomosis leakage were found. Additionally, the differences in weight and diameter of the sutures were not determined statistically significant.

Histological Evaluation

Adhesion Score (Fig. 1a, b)

Evaluation of Adhesion Formation

A pathologist blinded to the methods and groups examined all the specimens. Through this examination, efficacy of the interaction among the chitosan, sutures, and cecum could be observed. The tissues were fixed in a 10% buffered formaldehyde solution. The tissues were then embedded in paraffin following dehydration. The 5-µm thick sections were stained with hematoxylin and eosin and then evaluated by light microscopy at a magnification of 200×. The histopathological grading was performed with a modified Ehrlich and Hunt numerical scale (Table 2).[10]

In Vivo and In Vitro evaluation of Sutures’ Tensile Strength The anastomotic site surrounding the sutures was resected as a 4×3-cm wide strip for tensile strength. The sutures were then separated from the tissue for in vivo measurements.

Also, Vicryl and PDS sutures were put into serum for in vitro measurements until the 7th and 14th days.

The tests were evaluated in an Instron (Norwood, MA, USA) 4,301 instrument at room temperature, 21°C. The force employed was 5 kN/min. This action was established in the longitudinal direction in order to maintain the maximum strength at disruption.[5] Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

The adhesion score groups were listed in Table 3. When the adhesion scores on the 7th and 14th days were evaluated, a significant difference between the suture groups was not identified (p>0.05). The adhesion score of Vicryl and PDS groups were higher than the chitosan and control groups when comparing each on the 7th day (p<0.05). Also, there was no significant difference between the chitosan and control groups. Even though the adhesion score of the chitosan and control groups was lower than suture groups, the PDS group adhesion score was statistically higher than chitosan on the 14th day (p<0.05). In addition, clinically the adhesion scores of chitosan-coated Vicryl and PDS groups observed a minimal decrease at the 14th day compared with the 7th day. (a)

(b)

Figure 1. The intra-abdominal adhesion of (a) the Vicryl suture and (b) PDS suture.

407

Altınel et al. Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis

Table 3. The scores of adhesions

Control

Chitosan

Vicryl

Polydioxanone

Vicryl Chitosan

Polydioxanone Chitosan

p*

7th

0 (0–1)

0 (0–1)

2.5 (1–3)

2 (1–3)

1 (0–2)

1.5 (0–2)

<0.001*

14th

1 (0–1)

0 (0–1)

1 (1–2)

2 (1–3)

0.5 (0–2)

1 (0–2)

0.012*

p

0.234

1

0.094

0.383

0.281

0.279

*Statistically significant.

Table 4. Comparison of 7th and 14th day histopathological values of groups

Chitosan

Vicryl

Polydioxanone

Vicryl Chitosan

Polydioxanone Chitosan

p

Inflammatory cell

7th day

1.25 (1–2)

3 (2–3)

3 (2–3)

2 (2–3)

3 (3–3)

<0.001*

14 day

1.5 (1–3)

3 (2–3)

3 (2–3)

2.5 (2–3)

3 (2–3)

0.011*

p

th

0.645

0.779

1

0.867

0.234

Fibroblast 7th day

0.87 (0–2)

2 (1–3)

2 (0–3)

1 (0–2)

2 (1–2)

0.019*

14th day

0.87 (0–2)

2 (2–3)

2 (2–2)

1 (1–2)

2 (1–2)

<0.001*

p

1

0.281

0.383

0.867

0.442

Neovascularization 7 day

0.75 (0–2)

2 (1–2)

2 (1–3)

1 (0–2)

2 (1–2)

0.010*

14 day

1.75 (1–3)

2 (2–3)

2 (1–2)

1 (1–2)

2 (2–2)

0.013*

p

th

th

0.5

0.072

0.71

0.613

0.234

Collagen 7th day

0.75 (0–2)

0.5 (0–1)

1 (0–2)

0 (0–0)

3 (0–3)

0.009*

14th day

1.125 (0–2)

1 (0–1)

0 (0–1)

0 (0–1)

0 (0–1)

0.025*

p

0.328

0.867

0.318

0.463

0.442

*

Statistically significant.

Histopathology (Fig. 2a, b) The histopathological evaluation was shown in Table 4. The fibroblast cell accumulation and vascularization on the 14th day in the Vicryl–chitosan group were significantly lower than those in the Vicryl group (p=0.009) compared with the other suture groups. Additionally, the vascularization of the Vicryl–chitosan group was observed significantly lower than (a)

the PDS–chitosan group on the 14th day (p=0.038). However, there wasn’t any statistical difference between suture groups on the 7th day among inflammatory changes (p>0.05).

Histopathologically, no statistically significant difference was observed between suture groups of anastomosis for inflammatory cell and collagen accumulation (p>0.05). However, the chitosan group had a lower amount of neovascularization, (b)

Figure 2. The inflammatory cell infiltration of (a) the Vicryl suture (H&E 10) and (b) PDS suture (H&E 10).

408

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Altınel et al. Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis

Table 5. The tensile strength of sutures (MPa) as median (min–max) value 7th

14th p

Vicryl

In vivo

0.0214 (0.019–0.0256)

0.0165 (0.0159–0.0172)

<0.001*

In vitro

0.0184 (0.0183–0.0188)

0.0017 (0.0016–0.0018)

<0.001*

p

Polydioxanone

In vivo

0.0195 (0.0176–0.0202)

0.012 0.018 0.0177 (0.0162–0.0188)

0.007*

In vitro

0.0256 (0.0251–0.0262)

0.0025 (0.0024–0.0026)

0.001*

p

Vicryl Chitosan

In vivo

0.0194 (0.0161–0.0249)

0.01535 (0.0125–0.0208)

0.021*

In vitro

0.0246 (0.0231–0.0261)

0.02465 (0.0236–0.0257)

0.694

*

*

0.018* 0.018*

p

Polydioxanone Chitosan

In vivo

0.017 (0.0156–0.0176)

0.028 0.012 0.016 (0.0149–0.0174)

0.161

In vitro

0.0252 (0.025–0.0254)

0.0023 (0.002–0.0025)

<0.001*

p

*

*

0.012* 0.012*

p <0.05* <0.05* Statistically significant.

*

In Vivo and In Vitro Evaluation of Sutures’ Tensile Strength

decreased in vivo (p=0.021) more than the 7th day, but there was no statistical difference in vitro (p=0.694). The tensile strength of Vicryl–chitosan had significantly increased in vitro (p<0.05) more than Vicryl on the 14th and 7th days, but there was no statistical difference in vivo. The tensile strength of Vicryl–chitosan had decreased in vitro more than PDS–chitosan’s on the 7th day, but Vicryl–chitosan was statistically more than PDS–chitosan’s tensile strength in vivo (p=0.09) on the 7th day. Vicryl–chitosan had significantly increased in vitro (p<0.05) more than PDS–chitosan’s tensile strength on the 14th day, but there were no significant differences in vivo.

The tensile strength data for these groups were arranged in Table 5.

DISCUSSION

fibroblast, and inflammatory cell accumulation and higher amount of collagen accumulation than the suture groups on the 7th and 14th days (p<0.05). It was evident that the chitosan had an influence over the Vicryl suture causing minimal decrease among fibroblast, inflammatory cell and collagen accumulation including vascularization on the 14th day. However, no histopathological major change was observed among the chitosan effect on the PDS suture on the 14th day (p>0.05).

The tensile strength of Vicryl was statistically lower than PDS in vivo and in vitro on the 14th day and the 7th day (p<0.05).

The tensile strength of the PDS’s 14th day was lower than PDS’s 7th day, in vivo (p=0.007) and in vitro (p=0.001). The tensile strength of Vicryl’s 14th day was lower than Vicryl’s 7th day, in vivo and in vitro (p<0.001).

The chitosan decreased the tensile strength of PDS after coating in vivo and in vitro on the 7th and 14th days. Even if the tensile strength of PDS–chitosan decreased in vitro more than PDS on 7th day, statistically significant decline was seen in vivo (p<0.05). However, the tensile strength of PDS–chitosan decreased more on the 14th day than on the 7th day in vivo (p=0.161); hence, a significant decline was seen in vitro (p<0.001).

The chitosan decreased the tensile strength of Vicryl after coating in vivo but increased the tensile strength of Vicryl after coating in vitro on the 7th and 14th days. The tensile strength of Vicryl–chitosan on the 14th day had significantly Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

The chitosan coating on multifilament sutures such as VicrylTM (Ethicon, Somerville NJ) and monofilament PDSTM (Ethicon, Somerville NJ) was evaluated according to adhesion formation, histopathology, and tensile strength. In our experimental model, the coating of sutures with chitosan provided clinically beneficial effects to intra-abdominal adhesion formation. Moreover, when we respectively considered the evaluation of tensile strength in vivo and in vitro, we realized that there are some different interactions between the biocompatibility of sutures.

Chitosan has an essential effect on the inhibition of fibroblast migration and the reduction of collagen deposition at the surgical site.[11–13] The modified chitosan films such as 100% chitosan film, forms containing 10% or 50% gelatin, N, O-carboxymethyl chitosan gel and NOCC 2% solution forms were used in some of the experimental models. The modified chitosan film and gelatin forms have an effect on preventing peritoneal adhesions.[14–16] In vivo and in vitro the intestine tissue was repaired by laser-activated chitosan adhesive for achiev409

Altınel et al. Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis

ing the repair strength.[17] Furthermore, one of the features of chitosan is its hemostatic potential to prevent postoperative intra-abdominal bleeding which is a stimulus for adhesion.[8] However, similar to the study of the chitosan coating over meshes,[5] we did not observe any statistically significant decrease in peritoneal adhesion formation after the application of a chitosan on the sutures when compared to the uncoated forms. We can only mention that the beneficial influence of chitosan clinically observed during one of the inflammatory processes of adhesion formation had a collaborative effect on anastomosis strength.

In addition to that, there was not enough statistically significant difference between suture groups related to anastomosis for inflammatory cell and collagen accumulation in our study. The vascularization of Vicryl–chitosan group was observed to be significantly less than Vicryl and PDS–chitosan.

In addition, the fibroblast cell accumulation of Vicryl–chitosan group is significantly less than Vicryl on the 14th day. Due to this, a correlation could be made that the tensile strength of chitosan-coated Vicryl might be decreased in vivo. Our results could be due to the interaction of the chitosan coating and the property of multifilament VicrylTM. The fibroblast cell accumulation associated with inflammation promotes the adhesion formation and fibrosis involving collagen accumulation.[7,18] The adhesion score was lower in the chitosan group, although the suture groups were not strongly affected by the chitosan coating. However, it was estimated that the insufficient determination of the pathological results for anastomosis strength could be dependent on the amount of chitosan, the technique of coating or the type of suture material.

Moreover, there are many different biological and artificial materials for the prevention of anastomotic leakage and the reinforcing of anastomosis by covering it, like Bio-Gide, grafts, meshes,[2] which have been investigated. In addition, the bio-sutures like the mesenchymal stem cell-coated suture,[19] albumin-coated bioactive suture,[20] IGF-1-coated sutures,[21] protein-coated sutures[22] were used in various types of wound-healing processes. Some treatment effects of the resveratrol, gentamicin, fibrin glue, and butyrate on the healing of colonic anastomosis were performed in the studies.

[1,23] In our experiment, we evaluated the multifilament and monofilament sutures by coating with chitosan to encourage the cellular adhesion via inflammatory processes for reinforcing the anastomosis.

On the other hand, the weakest but main difference of our study compared with others is related to the evaluation of the bursting pressure of anastomosis.[24] The lack of proof by one of the measurements is the bursting pressure of the anastomotic strength.[25] When we investigated the breaking strength of anastomosis, we determined the tensile strength of sutures by evaluating the tensile strength of sutures in vivo and in vitro. We observed that chitosan interaction was more evident at chitosan-coated Vicryl in vitro and chitosan410

coated PDS in vivo. Although there were few different examples of chitosan biocompatibility or Nano-technics including electrospinning and new approaches to the development of suture materials.[26,27] According to recent experiments, as we observed, the newly developed suture coating process concludes as a promising method for obtaining a beneficial antibacterial effect. Similarly, to our study, it appears that the coating slightly improved the tensile strength of the sutures after the application of natural coatings on non-absorbable sutures.[28,29] Consequently, the results of our experiment did partially support our hypothesis. The chitosan coating over the sutures ameliorates the adhesion scores, the tensile strength, or the histopathological criteria in some parts over the reinforcement of anastomosis. The chitosan coating on the adhesion potential has shown clinically beneficial effects compared to statistical results. In addition, the chitosan improved the reinforcement of anastomosis in some parts of Vicryl in vitro and PDS in vivo. It is obvious that further investigations are required for the definitive clinical usage with new technical approaches for the chitosan-coated sutures among the anastomosis reinforcement. Moreover, there will be new challenges to create different suture properties.

Acknowledgments This study was presented as a poster at the ESCP 8th Scientific and Annual Meeting, 25–27 September 2013, Belgrade.

Conflict of interest: None declared.

REFERENCES 1. Subhas G, Bhullar JS, Cook J, Shah A, Silberberg B, Andrus L, et al.

Topical gentamicin does not provide any additional anastomotic strength when combined with fibrin glue. Am J Surg 2011;201:339–43.

2. Hoeppner J, Willa K, Timme S, Tittelbach-Helmrich D, Hopt UT, Keck T, et al. Reinforcement of colonic anastomoses with a collagenous doublelayer matrix extracted from porcine dermis. Eur Surg Res 2010;45:68– 76.

3. Kim JC, Lee YK, Lim BS, Rhee SH, Yang HC. Comparison of tensile and knot security properties of surgical sutures. J Mater Sci Mater Med 2007;18:2363–9.

4. Hernandez KA, Hooper RC, Boyko T, Golas AR, van Harten M, Wu DQ, et al. Reduction of suture associated inflammation after 28 days using novel biocompatible pseudoprotein poly(ester amide) biomaterials. J Biomed Mater Res B Appl Biomater 2015;103:457–63.

5. Altınel Y, Öztürk E, Özkaya G, Akyıldız EÜ, Ulcay Y, Özgüç H. The effect of a chitosan coating on the adhesive potential and tensile strength of polypropylene meshes. Hernia 2012;16:709–14.

6. Altınel Y, Taşpınar E, Ozgüç H, Oztürk E, Ulker Akyıldız E, Bağdaş D. The protective effect of ClinOleic against post-surgical adhesions. Ulus Travma Acil Cerrahi Derg 2014;20:1–6.

7. Gómez-Estaca J, López de Lacey A, López-Caballero ME, Gómez-Guillén MC, Montero P. Biodegradable gelatin-chitosan films incorporated with essential oils as antimicrobial agents for fish preservation. Food Microbiol 2010;27:889–96.

8. Ong SY, Wu J, Moochhala SM, Tan MH, Lu J. Development of a chi-

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Altınel et al. Effect of chitosan coating on surgical sutures to strengthen the colonic anastomosis tosan-based wound dressing with improved hemostatic and antimicrobial properties. J Biomaterials 2008;29:4323–32.

9. Schneider A, Bennek J, Olsen K. Experimental study evaluating the effect of a barrier method on postoperative intraabdominal adhesions. Dig Dis Sci 2006;51:566–70.

10. Phillips JD, Kim CS, Folkalsrud EW. Effects of chronic corticosteroids and vitamin A on the healing of intestinal anastomoses. Am J Surg 1992;163:71–7.

11. Zhou J, Elson C, Le TD. Reduction in postoperative adhesion formation and re-formation after an abdominal operation with the use of N, O carboxymethyl chitosan. J Surg 2004;135:307–12.

12. Risbud M, Hardikar A, Bhonde R. Growth modulation of fibroblasts by chitosan-polyvinyl pyrrolidone hydrogel: implications for wound management? J Biosci 2000;25:25–31.

13. van der Wal JB, Jeekel J. Biology of the peritoneum in normal homeostasis and after surgical trauma. Colorectal Dis 2007;9:9–13.

14. Zhang Z, Xu S, Zhou XL. Preventive effects of chitosan on peritoneal adhesion in rats. W J Gastroenterol 2006; 28:4572–77.

15. Zhou X, Chen S, Liao G, Shen ZJ, Zhang ZL, Sun L, et al. Preventive effect of gelatinizedly-modified chitosan film on peritoneal adhesion of different types. World J Gastroenterol 2007;13:1262–67.

16. Costain DJ, Kennedy R, Ciona C McAlister VC, Lee TD. Prevention of postsurgical adhesions with N,O-carboxymethyl chitosan: examination of the most efficacious preparation and the effect of N,O-carboxymethyl chitosan on postsurgical healing. J Surg 1997;121:314–19.

17. Lauto A, Stoodley M, Marcel H, Avolio A, Sarris M, McKenzie G, et al.

In vitro and in vivo tissue repair with laser-activated chitosan adhesive.

Lasers Surg Med 2007;39:19–27.

18. Bachman S, Ramshaw B. Prosthetic material in ventral hernia repair: how do I choose? Surg Clin N Am 2008;88:101–12.

19. Pascual I, Fernández de Miguel G, García Arranz M, García-Olmo D. Biosutures improve healing of experimental weak colonic anastomoses.

Int J Colorectal Dis 2010;25:1447–51.

20. Horváthy DB, Vácz G, Cselenyák A, Weszl M, Kiss L, Lacza Z. Albumin-coated bioactive suture for cell transplantation. Surg Innov 2013;20:249–55.

21. Rijcken E, Fuchs T, Sachs L, Kersting CM, Bruewer M, Krieglstein CF. Insulin-like growth factor 1-coated sutures improve anastomotic healing in an experimental model of colitis. Br J Surg 2010;97:258–65.

22. Mazzocca AD, McCarthy MB, Arciero C, Jhaveri A, Obopilwe E, Rincon L, et al. Tendon and bone responses to a collagen-coated suture material.

J Shoulder Elbow Surg 2007;16:222–30.

23. Cakmak GK, Irkorucu O, Ucan BH, Tascilar O, Emre AU, Karakaya K, et al. The effects of resveratrol on the healing of left colonic anastomosis.

J Invest Surg 2009;22:353–61.

24. Månsson P, Zhang XW, Jeppsson B, Thorlacius H. Anastomotic healing in the rat colon: comparison between a radiological method, breaking strength and bursting pressure. Int J Colorectal Disease 2002;17:420– 5.

25. Posma LA, Bleichrodt RP, Lomme RM, de Man BM, van Goor H, Hendriks T. Early anastomotic repair in the rat intestine is affected by transient preoperative mesenteric ischemia. J Gastrointest Surg 2009;13:1099–106.

26. Sanders D, Lambie J, Bond P, Moate R, Steer JA. An in vitro study assessing the effect of mesh morphology and suture fixation on bacterial adherence. Hernia 2013;17:779–89.

27. Norowski PA, Mishra S, Adatrow PC, Haggard WO, Bumgardner JD. Suture pullout strength and in vitro fibroblast and RAW 264.7 monocyte biocompatibility of genipin crosslinked nanofibrous chitosan mats for guided tissue regeneration. J Biomed Mater Res A 2012;100:2890–6.

28. Debbabi F, Gargoubi S, Hadj Ayed MA, Abdessalem SB. Development and characterization of antibacterial braided polyamide suture coated with chitosan-citric acid biopolymer. J Biomater Appl 2017;32:384–98.

29. Masood R, Hussain T, Umar M, Azeemullah, Areeb T, Riaz S. In situ development and application of natural coatings on non-absorbable sutures to reduce incision site infections. J Wound Care 2017;26:115–20.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Kitosan kaplı ipliklerin anastomoz gücü arttırma üzerine etkisi Dr. Yüksel Altınel,1 Dr. Soon Soup Chung,2 Dr. Güven Okay,3 Dr. Nesrin Uğraş,4 Dr. Ahmet Fatih Işık,5 Dr. Ersin Öztürk,1 Dr. Halil Özgüç1 Uludağ Üniversitesi Tip Fakültesi, Genel Cerrahi Anabilim Dalı, Bursa Ewha Üniversitesi Hastanesi, Genel Cerrahi Anabilim Dalı, Seul-Kore 3 Uludağ Üniversitesi Tip Fakültesi, Biostatistics Anabilim Dalı, Bursa 4 Uludağ Üniversitesi Tip Fakültesi, Patoloji Anabilim Dalı, Bursa 5 Uludağ Üniversitesi Tekstil Mühendisliği Fakültesi, Tekstil Anabilim Dalı, Bursa 1 2

AMAÇ: Yara iyileşmesi etkisiyle, kitosan kaplı ipliklerin bağırsak anastomozu gücü üzerine uygulanabilir olmasını araştırdık.

GEREÇ VE YÖNTEM: Vikril ve PDS iplikler %2 kitosanla kaplandı. Laparatomi birinci gruba uygulanırken, kitosan ikici grupta periton boşluğuna uygulandı. Takibinde sırasıyla vikril, PDS, kitosan kaplı vikril ve kitosan kaplı PDS iplikler kolon anastomozunda kullanıldı. Yedinci ve 14. günlerde her gruptan sekiz sıçan sakrifiye edilerek incelemesi yapıldı.

BULGULAR: Kitosan ve kontrol grubunun adezyon değeri iplik gruplarına göre anlamlı olarak daha düşük saptandı (p<0.05). Kitosan kaplı vikril grubunun 14. günde vaskülarizasyon değeri, kitosan kaplı PDS iplik grubuna göre anlamlı olarak daha az olduğu belirlendi (p=0.038). Kitosan kaplı vikrilin 14. gücünde, anastomoz vaskülarizasyonu ve fibroblast hücreleri üzerinde vikril ve kitosan kaplı PDS göre etkisi daha düşük bulundu (p<0.05). Kitosan kaplı vikrilin 14. ve yedinci günündeki in vitro mukavemet gücü vikrilden daha yüksek olmasına rağmen (p<0.05), in vivo farklılık görülmedi. The PDS-kitosan’ın mukavemet gücü in vivo yedinci günde, PDS’den daha az olarak saptandı (p<0.05).

TARTIŞMA: Kitosan ile kaplama, anastomoz gücünü ve adezyon etkisini hafif oranda in vitro vikril ve in vivo PDS üzerinde arttırdı.

Anahtar sözcükler: Anastomoz; kitosan; mukavemet gücü, PDS ve Vicryl iplikler; yara iyileşmesi.

Ulus Travma Acil Cerrahi Derg 2018;24(5):405-411

doi: 10.5505/tjtes.2018.59280

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

411

ORIG I N A L A R T IC L E

Efficacy of negative pressure wound therapy in the management of acute burns Metin Kement, M.D.,1

Adil Başkıran, M.D.2

1

Department of General Surgery, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

2

Department of General Surgery, İnönü University Faculty of Medicine, Malatya-Turkey

ABSTRACT BACKGROUND: The aim of the present study was to evaluate the outcomes and efficacy of negative pressure wound therapy in the management of acute burns.

METHODS: Patients with acute burns who have received negative pressure wound therapy at the Dr. Lutfi Kırdar Kartal Research and Training Hospital Tertiary Burn Care Center between January 2014 and December 2015 were included in the study. Patient data were retrospectively reviewed by analyzing data from our prospective patient database.

RESULTS: A total of 38 patients were evaluated for the study. Three patients were excluded due to mortality prior to the completion of the treatment course. There were 32 (91.6%) male and 3 (8.4%) female patients. The mean age of the patients was 49.5±16 years.

The etiological factors included electrical burn injury in 19 (54.3%), chemical burn injury in 7 (20%), flame burn injury in 6 (17.2%), and hot water burns in 3 (8.4%) patients. The severity of the burns was grade 3 or 4 in all of the patients included in the study. The mean duration of negative pressure wound therapy was 10.1±3.9 days. There were no procedure-related complications throughout the duration of the study. During the standard application of the device, one patient experienced local pain; therefore, low pressure (75 mmHg) was applied during therapy, and pressure was steadily increased. As a result of the application of this therapy, a decrease in the surface area, edema, and secretion of the wound and an increase in the granulation tissue and perfusion of the wound were observed in all treated patients. Wound cultures revealed no bacterial growth in any of the patients. The mean duration of surgical wound closure was 11.2±3.7 days. No complication was observed related to wound closure. The mean duration of hospital discharge in the postoperative period was 6.7±2.1 days.

CONCLUSION: Well-designed, randomized control studies showing the efficacy of negative pressure wound therapy in patients with burns are lacking. The results of the present study showed that negative pressure wound therapy may reduce the number of wound debridement sessions, time of wound closure, and hospitalization in major burn injuries exposing the underlying tendons and bones.

Keywords: Burn; grafting; negative pressure wound therapy.

INTRODUCTION The increased risk of infection and delay in wound healing are the main problems in burns, especially in cases with exposure of the tendon and bone. During the management of such wounds, skin grafts and flaps are used for wound closure. However, occasionally, the condition of the wound in the early phases is not eligible for the application of such

therapies. Therefore, long-term open wound care and wound dressings are used as a bridging therapy. In addition, despite adequate therapy, some cases do not meet the adequate conditions for wound closure.[1] Negative pressure wound therapy is a non-invasive therapeutic method that supports the healing of acute and chronic non-healing wounds.[2] It was first described by Argent and

Cite this article as: Kement M, Başkıran A. Efficacy of negative pressure wound therapy in the management of acute burns. Ulus Travma Acil Cerrahi Derg 2018;24:412-416.

Address for correspondence: Adil Başkıran, M.D. İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya, Turkey Tel: +90 422 - 341 06 60 E-mail: dr.adil.baskiran@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):412-416 DOI: 10.5505/tjtes.2017.78958 Submitted: 10.12.2017 Accepted: 26.12.2017 Online: 20.03.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

412

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Kement et al. Efficacy of negative pressure wound therapy in the management of acute burns

Morykwas et al.[3,4] in experimental and clinical models and became popular among physicians. The aim of the negative pressure wound therapy is to increase local blood supply, induce granulation tissue formation, and reduce the incidence of infection.[2,5] The aim of the present study was to evaluate the outcomes and efficacy of negative pressure wound therapy in the management of acute burns.

MATERIALS AND METHODS Patients Patients with acute burns who have received negative pressure wound therapy at the Dr. Lutfi Kırdar Kartal Research and Training Hospital Tertiary Burn Care Center between January 2014 and December 2015 were included in the present study. Patient data were retrospectively reviewed by analyzing data from our prospective patient database. Patients with an American Society of Anesthesiologists IV score, pediatric patients who were <12 years old, patients with concomitant organ system injury, and patients who died during treatment were excluded from the study.

Negative Pressure Wound Therapy System In the present study, negative pressure wound therapy was applied using the vacuum-assisted wound closure (VAC) system (Kinetic Concept, Inc., USA). The components of the system include a sponge to cover the wound surface, drape to cover the sponge and the wound, connectors between the wound and the device (Therapeutic Regulated Accurate Care— T.R.A.C. pad), collectors, and negative pressure device.

Application In all patients, escharotomy and wound debridement were performed in the operating room. At the end of the surgical steps, the sponges were shaped according to the size of the wound and used to cover the surface of the wound.

The drapes were applied in order to cover the wound and sponges. A hole is punched on the drape, and T.R.A.C. pad is applied. The connectors are applied to the wound and the VAC device. The negative pressure setting is adjusted to 100– 150 mmHg, and the device is turned on. The wound dressings were changed once in 72 h. The wound diameter, granulation tissue, and blood supply were evaluated in each wound care session. Wound debridement was applied when necessary.

Tissue cultures were obtained whenever the wound dressings were changed. Antibiotic therapy was started and changed according to the results of these cultures. VAC therapy was continued until the wound surface and granulation were eligible for surgical closure methods. In each step, the condition of the wounds was documented.

Study Parameters The study parameters included demographic data, such as age Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

and gender, and clinical parameters, such as mechanism of the burn, localization of the wound, duration of VAC therapy, duration of therapy in general, and techniques of final wound closure.

Statistical Analysis Continuous data were expressed as mean and standard deviation. Qualitative data were expressed as numbers and percentages. All the statistical procedures were performed using the Statistical Package for the Social Sciences software package version 17.0 (IBM, USA).

RESULTS A total of 38 patients were evaluated for the study. Of the patients, three were excluded due to mortality before completing the treatment course. Of 35 patients, 32 (91.6%) were males, and 3 (8.4%) were females. The mean age of the patients was 49.5±16 years. Table 1 shows the demographic and clinical characteristics of the patients. The etiological factors included electrical burn injury in 19 (54.3%), chemical burn injury in 7 (20%), flame burn injury in 6 (17.2%), and hot water burns in 3 (8.4%) patients. The severity of the burns ranged from grade 3 to 4 in all of the patients included in the study. The mean duration of negative pressure wound therapy was 10.1±3.9 days (Table 1). No procedurerelated complications throughout the duration of the study were observed. One patient experienced local pain during the standard application of the device; thus, low pressure (75 mmHg) was applied during therapy, and pressure was gradually increased. Reduction in the surface area, edema, and secretion of the wound and elevation in the granulation tissue and perfusion of the wound are observed in all patients treated using this therapy (Fig. 1). Wound cultures showed no bacterial growth in any of the patients. The mean duration of surgical wound closure was 11.2±3.7 days. There was no complication related to wound closure. The mean duration of hospital discharge in the postoperative period was 6.7±2.1 days.

DISCUSSION Burn injury affects all the physiological systems of the organism, and the patient should be thoroughly evaluated. It (a)

(b)

Figure 1. The figure shows a major grade 4 burn injury of the hand exposing the tendon (a) and the condition of the wound after two sessions of negative pressure wound therapy (b).

413

Kement et al. Efficacy of negative pressure wound therapy in the management of acute burns

Table 1. Characteristics of the patients analyzed in the study Diagnosis

Gender

Age

Period of VAC

Affected region

Wound closure technique

Concomitant disease

Flame injury

Male

29

3x3=9

Hand-Forearm

Graft

No

Male 13 2x3=6

Foot

Graft

No

Male 36 5x3=15

Thigh

Graft

No

Male 35 3x3=9

Leg

Flap+graft

No

Male 50 3x3=9

Forearm

Graft

No

Male

35

4x3=12

Bilateral thigh

Graft

No

Electric injury

Male

65

3x3=9

Foot

Flap+graft

No

Male 15 7x3=21

Foot

Graft

No

Male 31 1x3=3

Leg

Graft

No

Male 23 3x3=9

Leg

Graft

No

Male 31 5x3=15

Foot

Graft

No

Male 41 5x3=15

Foot

Graft

No

Male 51 2x3=6

Forearm

Flap

No

Thigh

Flap

Neurologic

Female 52

5x3=15

Male 45 5x3=15

Foot

Graft

No

Male 70 3x3=9

Leg

Graft

No

Male

67

4x3=12

Bilateral leg

Graft+suture

No

Male

45

2x3=6

Arm and forearm

Graft

No

Male 54 2x3=6 Female 59

4x4=16

Leg

Amputation

No

Foot

Flap+graft

No

Male 66 3x3=9

Foot

Flap

No

Male 55 3x3=9

Leg

Graft

No

Male 70 3x3=9

Foot

Graft

No

Male 38 2x3=6

Foot

Graft

No

Male 70 5x3=15

Foot

Graft

No

Chemical injury

Male

Hand

Finger amputation

No

Male 63 3x3=9

Elbow+forearm

Graft

No

Male 68 3x3=9

Foot

Graft+amput

DM

Male 55 4x3=12

Scalp

Graft

No

Male 58 3x3=9

Hand

Flap+graft

No

Male 60 3x3=9

Foot

Graft

No

Hot water burns

Male

Graft

No

Male 67 3x3=9

Leg

Graft

No

Male 65 4x3=12

Leg

Graft

DM

Leg

Flap+graft

No

55

49

Female 45

3x3=9

3x3=9

1x3=3

Forearm

VAC: Vacuum Assisted Wound Closure; DM: Diabetes mellitus.

has a major impact on society and has great morbidity and mortality. Major burns have 6% mortality even in developed countries. In Turkey, the mortality rate has been reported at 7.5% in recent studies.[6,7] In the USA, it has been reported that treatment of a patient with major burns costs $200,000.

Globally, there are multidisciplinary studies that are being performed to increase the efficacy and reduce the costs of burn treatment.[1,8] 414

Tissue injury in patients with burns results in regional edema in the soft tissue. Burn injury leads to capillary leak and results in accumulation of fluids in the interstitial space, resulting in edema.[9] Edema changes the morphology and function of the cells and results in enhanced tissue damage. Edema in the interstitial space causes mechanical compression on the vessel wall and reduces the vascular supply of the tissue.

Furthermore, it increases the diffusion distance in the interUlus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Kement et al. Efficacy of negative pressure wound therapy in the management of acute burns

stitial space, and all these changes result in cellular hypoxia and progressive tissue damage.

Negative pressure wound therapy reduces edema and results in many physiological changes that enhance wound healing.

Morykwas et al.[3] performed Doppler flow meter in a skin defect model and showed that a negative pressure of 125 mmHg results in four times increase in tissue blood flow.[1] Negative pressure wound therapy enhances tissue perfusion, and capillary density of the tissue increases and results in reduced tissue edema.[10,11] Mechanical stress to the endothelium results in the secretion of certain cytokines and cellular factors and results in endothelial proliferation and neoangiogenesis. Enhanced perfusion and reduced edema provide a perfect milieu for granulation tissue to develop rapidly.[10,11] Negative pressure wound therapy eliminates local bacteria, reduces proteases that prevent wound healing, enhances wound healing, and reduces healing time.[8–12] The efficacy of negative pressure wound therapy has been proven in patients with diabetic foot and abdominal compartment syndrome.[13] Negative pressure wound therapy has two types of applications in the management of patients with burns. In the initial approach, such as ours, negative pressure wound therapy is applied primarily. In the second approach, it can be applied after grafting of the wound area.[14] Although randomized well-designed studies supporting the primary use of negative pressure wound therapy are lacking, there are many minor reports and case series supporting the efficacy of this approach that reduces the grafting time of the wound.[15] To our knowledge, the present study is the largest case series in the literature that has employed VAC in patients with major burns. Negative pressure wound therapy has enhanced granulation formation, reduced edema, and reduced bacterial load in our series. Only one case reported pain due to the application of standard negative pressure wound therapy, and it was resolved following reduction of pressure in this patient.

The major limitation of our study is the lack of a control group due to the retrospective design of the study. Furthermore, we did not obtain tissue biopsy for the histological evaluation of the effects of negative pressure therapy.

Conclusions Well-designed, randomized control studies showing the efficacy of negative pressure wound therapy in patients with burns are lacking. The results of the present study showed that negative pressure wound therapy may reduce the num-

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

ber of wound debridement sessions, time of wound closure, and hospitalization in major burn injuries exposing the underlying tendons and bones.

Conflict of interest: None declared.

REFERENCES 1. Etöz A, Özgenel GY, Özcan M. Application of Negative Pressured Dressing: Our Clinical Experiences [Article in Turkish]. Türk Plast Rekonstr Est Cer Derg 2004;12:102–5.

2. DeFranzo AJ, Argenta LC, Marks MW, Molnar JA, David LR, Webb LX, et al. The use of vacuum-assisted closure therapy for the treatment of lower-extremity wounds with exposed bone. Plast Reconstr Surg 2001;108:1184–91.

3. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuumassisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg 1997;38:553–62.

4. Arcenta LC, and Morkywas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 1997;38:563–77.

5. Voinchet V, Magalon G. Vacuum assisted closure. Wound healing by negative pressure [Article in French]. Ann Chir Plast Esthet 1996;41:583–9.

6. Monafo WW. Initial management of burns. N Engl J Med 1996;335:1581–6.

7. Gomez M, Cartotto R, Knighton J, Smith K, Fish JS. Improved survival following thermal injury in adult patients treated at a regional burn center. J Burn Care Res 2008;29:130–7.

8. Venturi ML, Attinger CE, Mesbahi AN, Hess CL, Graw KS. Mechanisms and clinical applications of the vacuum-assisted closure (VAC) Device: a review. Am J Clin Dermatol 2005;6:185–94.

9. Gibran NS, Heimbach DM. Current status of burn wound pathophysiology. Clin Plast Surg 2000;27:11–22 10. Coles DR, Greenfield AD. The reactions of the blood vessels of the hand during increases in transmural pressure. J Physiol 1956;131:277–89.

11. Urschel JD, Scott PG, Williams HTG. The effect of mechanical stress on soft and hard tissue repair; a review. Br J Plast Surg 1988;41:182–6.

12. Li XY, Li WZ, Li YJ, Lv XX, Li J, Chen SZ, Li JQ. The influence of vacuum-assisted drainage on the growth of capillaries in the wound produced by explosion in pig [Article in Chinese]. Zhonqhua Shao Shang Za Zhi 2007;23:292–5.

13. Xie X, McGregor M, Dendukuri N. The clinical effectiveness of negative pressure wound therapy: a systematic review. J Wound Care 2010;19:490–5.

14. Kamolz LP, Lumenta DB, Parvizi D, Wiedner M, Justich I, Keck M, et al.

Skin graft fixation in severe burns: use of topical negative pressure. Ann Burns Fire Disasters 2014;27:141–5.

15. Adámková M, Tymonová J, Zámecníková I, Kadlcík M, Klosová H. First experience with the use of vacuum assisted closure in the treatment of skin defects at the burn center. Acta Chir Plast 2005;47:24–7.

415

Kement et al. Efficacy of negative pressure wound therapy in the management of acute burns

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut yanıkların tedavisinde negatif basınçlı yara terapisinin etkinliği Dr. Metin Kement,1 Dr. Adil Başkıran2 1 2

Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya

AMAÇ: Bu çalışmada, amacımız negatif basınçlı yara terapisinin (NBYT) akut yanıkların tedavisindeki sonuçları ve etkinliğinin araştırılmasıydı.

GEREÇ VE YÖNTEM: Bu çalışmaya, Ocak 2014 ile Aralık 2015 tarihleri arasında Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi Yanık Merkezi’nde yanık yarası sebebiyle NBYT uygulanan hastalar dâhil edildi. Hasta verileri ileriye yönelik olarak tutulan bir veritabanı kullanılarak geriye dönük olarak toplandı. Olguların; yaş, cinsiyet, yanık etiyolojileri, yara lokalizasyonları, VAC uygulama süreleri, genel tedavi süreleri, yara kapatma teknikleri geriye dönük olarak değerlendirildi.

BULGULAR: Çalışmaya alınan toplam 35 olgunun 32’si (%91.6) erkek, üçü (%8.4) kadındı. Hastaların genel yaş ortalamaları 49.5±16 (13–79) idi.

Etiyolojik faktörler sırasıyla 19 (%54.3) olguda elektrik çarpması, yedi (%20) olguda temas yanığı, altı (%17.2) olguda alev yanığı, üç (%8.6) olguda sıcak su şeklindeydi. Uygulama yapılan yaraların tümünde yanıklar 3. veya 4. derece idi. NBYT uygulama süremiz en az üç, en çok 16 gün olmak üzere ortalama 10.1±3.9 gündü. Hastaların hiçbirinde uygulamaya bağlı komplikasyon gelişmedi. Bir hastamızda standart basınçta uygulama sırasında lokal ağrı gelişmesi üzerine uygulamaya düşük basınç ile (75 mmHg) devam edilerek basınç kademeli olarak artırıldı. Uygulama sonucu tüm hastaların yara alanlarında küçülme, granülasyon dokusunda ve kanlanmada artma, ödem ve yara sekresyonunda azalma gözlemlendi. Hastaların hiçbirinde uygulama bölgesinde bakteriyal üreme tespit edilmedi. Tüm hastaların yaraları cerrahiye uygun olarak değerlendirilerek ortalama 11.2±3.7 günün sonunda greft veya flep yöntemlerinin biri kullanılarak kapatıldı. Hastaların hiçbirinde greft ya da flebe sekonder komplikasyon görülmedi. Hastalar ameliyat sonrası ortalama 6.7±2.1 (5–9 gün) günde taburcu edildi.

TARTIŞMA: Çalışmamızın bulguları ışığında, NBYT’nin iyileşmesi zor, derin, tendon ve kemik ekspoze olmuş yanıklarda yaranın kısa sürede greft ya da flepler ile kapatılmasına olanak vererek, pansuman sayısını ve hastanede yatış süresini azaltabilecek yardımcı bir tedavi seçeneği olabileceği söylenebilir. Ancak, halen daha literatürde NBYT’nin yanıkta kullanımı ile ilgili kanıt düzeyi yüksek ileriye yönelik, randomize, kontrollü çalışma eksikliğinin de mevcut olduğu vurgulanmalıdır.

Anahtar sözcükler: Graft; negatif basınçlı yara tedavisi; yanık.

Ulus Travma Acil Cerrahi Derg 2018;24(5):412-416

416

doi: 10.5505/tjtes.2017.78958

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

ORIG I N A L A R T IC L E

Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery Erol Kılıç, M.D.,

Mustafa Uğur, M.D.

Department of General Surgery, Mustafa Kemal University Faculty of Medicine, Hatay-Turkey

ABSTRACT BACKGROUND: Although therapeutic hypothermia has been shown to be effective on surgical site infection and postoperative pain in patients undergoing elective surgery, its exact effect on emergency laparotomy remains unclear. In this study, we aimed to investigate the effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in patients undergoing urgent open abdominal surgery.

METHODS: The study included 100 patients who underwent emergency open abdominal surgery from 01/01/2016 to 01/01/2017.

The patients were randomly divided into two groups: therapeutic hypothermia, group I underwent cold therapy with local sterile frozen ice compress; and control group II, underwent conventional sterile compress. Age, gender, primary pathology diagnosis, size of incision, wound type and size, and duration of surgery were compared between the groups. Visual analog scale scores were determined every 3 hours, and the requirement for analgesics was assessed for each patient within 48 hours postoperatively. Both before and after 5 days of laparotomy, c-reactive protein (CRP), white blood cell count (WBC), albumin, serum total antioxidant status, and total oxidant status levels were measured, and oxidative stress index was calculated for each patient. The rates of superficial surgical site infection were compared between both groups.

RESULTS: The two groups were similar in terms of age, gender, primary pathology diagnosis, size of incision, wound type and size, and duration of surgery (p>0.05). Although no significant difference was found between the groups with regards to visual analog scale scores (p>0.05), requirement for analgesics was lower in the group I compared to that in the control group (p<0.05). No significant difference was found between the groups in terms of preoperative WBC, albumin, CRP, serum total antioxidant status, total oxidant status, and oxidative stress index (OSI) levels (p>0.05). At postoperative day 5, serum total antioxidant status level was significantly higher, and OSI level was significantly lower in the group I compared to the respective levels in the control group (p<0.05). Moreover, the superficial surgical site infection rate was significantly lower in the group I (p<0.05).

CONCLUSION: In patients undergoing urgent open abdominal surgery, therapeutic hypothermia led to lower requirement for analgesics and lower superficial surgical site infection rates in the early postoperative period. We consider that therapeutic hypothermia exerts this effect by elevating the serum total antioxidant status level, and decreasing the effects of inflammatory mediators and OSI. Keywords: Postoperative pain; superficial surgical site infection; therapeutic hypothermia.

INTRODUCTION Therapeutic hypothermia (TH) was first described by Hippocrates. It was used for pain relief by ancient Egyptians, Persians, and Romans. TH is still used for pain relief in various injuries, diseases, and invasive approaches.[1–3] Hypothermia

exerts its analgesic effect through several mechanisms including sensory nerve inactivation, reduced nerve conduction velocity, activation of inhibitory interneurons (gate mechanism), opposite irritation, endorphin release, and by decreasing the cellular metabolism of enzyme activity.[4–7] Superficial surgical site infection (SSSI) is a clinical infection that commonly oc-

Cite this article as: Kılıç E, Uğur M. Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery. Ulus Travma Acil Cerrahi Derg 2018;24:417-422.

Address for correspondence: Erol Kılıç, M.D. Mustafa Kemal Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Hatay, Turkey Tel: +90 326 - 229 10 00 / 3368 E-mail: ekkilic55@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):417-422 DOI: 10.5505/tjtes.2018.23345 Submitted: 09.02.2018 Accepted: 31.07.2018 Online: 20.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

417

Kılıç et al. Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery

curs in the subcutaneous tissue of incision within 30 days after operative procedure.[8] SSSI is the most common nosocomial infection (30%) that causes high morbidity and mortality.[9] The SSSI rates have been reported to be 5% after aseptic procedures and up to 40% after abdominal procedures that cause contamination, such as colorectal surgery.[10] The effect mechanism of TH in the activation of the immune system against infection is well known: TH decreases the concentration of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-2 while increasing the release of anti-inflammatory cytokines such as IL-10.[11–13] Moreover, TH decreases the serum levels of traditional adhesion molecules that have a role in leukocyte transmigration (ICAM-1, E-Selectin, VCAM).[14–16] Literature reviews indicate that the effect of hypothermia on postoperative pain and surgical site infection has been extensively studied. However, to our knowledge, no study investigates the effect of hypothermia in patients undergoing emergency laparotomy who have been shown to have high rates of surgical site infection. Therefore, this study was aimed to investigate the effect of TH on SSSI and postoperative pain in such patients.

MATERIALS AND METHODS The study was designed as a single-center and double-blind study, and it was conducted at Mustafa Kemal University Medical School General Surgery Department following the approval of Mustafa Kemal University Clinical Research Ethics Committee (Approval date, January 17, 2015; No. 4298783/05003). The study was funded by Mustafa Kemal University Scientific Research Projects Directory (Decree No. 13660).

The study included 100 patients who underwent emergency laparotomy with midline incision within a period of 1 year from 01/01/2016 to 01/01/2017. Patients with a serious medical disease, obesity (BMI >35), malnutrition, cachexia (BMI <18), immunosuppression, and diabetes mellitus as well as and patients who were receiving corticosteroid treatment and had a history of smoking were excluded from the study.

Preoperative SSSI prophylaxis was performed with intravenous (IV) quinolone (ciprofloxacin, 200 mg IV) 60 min prior to the anesthetic induction. After the induction, the skin hair was removed using a shaving machine. All the surgical procedures were performed under general anesthesia. Anesthesia was induced with IV propofol (2 mg/kg), remifentanil (1 mcg/ kg), and rocuronium (0.6 mg/kg). Anesthesia was maintained with sevoflurane and 50% N2O in oxygen. At the end of the surgery, all the patients were administered tramadol 100 mg IV and acetaminophen 1 g for postoperative pain relief prior to extubation.

The patients were randomized by computer, and they were divided into two equal groups: (I) the TH group (n=50) un418

derwent TH within the first hour after the surgery, and (II) the control group (n=50) did not undertake TH. The TH group underwent cold therapy with local sterile frozen ice compress (Alkantis®, France), whereas the control group underwent conventional sterile compress. In both groups, wound dressing was changed every 3 hours, and the surgical site was left closed for 48 hours.

Age, gender, primary pathology diagnosis, history of diseases, preoperative antimicrobial treatment, total blood loss, requirement for blood transfusion, size of incision, and wound type and size were recorded for each patient. Visual analog scale (VAS) scores were determined every 3 h, and the requirement for nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid drugs was assessed for each patient within 48 h postoperatively. Patients with a VAS score of >4 were administered 75 mg diclofenac in a single intramuscular (IM) injection. If the VAS score was still >4 after 20 min, 1 mg/ kg of pethidine hydrochloride (Aldolan®) was infused in 50 cc saline solution for 10 min.

All the patients were planned for emergency laparotomy. Both before and after 5 days of the emergency laparotomy, c-reactive protein (CRP), white blood cell count (WBC), albumin, serum total antioxidant status (TAS), and total oxidant status (TOS) levels were measured, and oxidative stress index (OSI) was calculated for each patient. WBC was measured by a fully automated hematology analyzer (Mindray®, UK). Fasting venous blood samples were centrifuged at 1500 g, and serum was separated. Serum TAS and TOS levels were measured using the spectrophotometric method developed by Erel (Rel Assay Diagnostics Kits, Mega Tıp®, Turkey).[17,18] OSI was calculated based on the following formula: OSI (arbitrary unit) = TOS (μmol H2O2 Eq/L) / TAS (μmol Trolox Eq/L). Serum albumin levels were spectrophotometrically measured using an auto analyzer (ArchitectR c8000, Clinical Chemistry Analyzer, Abbott, USA), and serum CRP levels were measured using the nephelometric method (Immage Nephelometer®, Beckman Coulter Inc., USA).

SSSI was identified based on the Centers for Disease Control and Prevention’s National Healthcare Safety Network classification for surgical site infection, and was it followed up for 30 days postoperatively.[19] SSSI was accepted as clinical presentation of rash, edema, local heat elevation, and purulent discharge in the surgical site within this period, and culture analysis and treatment were performed accordingly.

Statistical Analysis Data were analyzed using SPSS 23 (IBM SPSS Statistics for Windows, Armonk, NY, USA). Normal distribution was tested using the Shapiro–Wilk Normality Test. Variables with normal distribution were compared using the t-test.

Variables with nonnormal distribution were compared using Mann–Whitney U test and Wilcoxon test. Categorical Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Kılıç et al. Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery

variables were analyzed using the chi-square test. Variables with normal distribution were expressed as mean ± standard deviation, and variables with nonnormal distribution were expressed as median (minimum-maximum). Categorical variables were expressed as frequencies and percentages. A p value of <0.05 was considered significant.

tion at 24–48 h postoperatively was significantly lower in the TH group compared to that in the control group (p<0.05).

Similarly, mean opioid drug consumption was significantly lower in the TH group both at 0–24 h and 24–48 h postoperatively compared to that in the control group (p<0.05) (Table 2).

RESULTS

SSSI was detected in 11 (22%) patients in the TH group and in 17 (34%) patients in the control group, and a significant difference was found between the two groups (p<0.05). Moreover, the pathogens isolated from surgical site infections were similar in both groups. The most common pathogen was methicillin-resistant staphylococcus aureus (MRSA), followed by coagulase-negative staphylococci (CoNS), enterococci, and Escherichia coli, respectively (Table 3).

The two groups were similar in terms of age, gender, primary pathology diagnosis, size of incision, and wound type and size, and duration of surgery (p>0.05) (Table 1). In addition, the groups were also similar with regards to wound size (cm), duration of surgery, preoperative TAS, TOS, OSI, albumin, CRP, and WBC levels, total blood loss, and requirement for blood transfusion (p>0.05) (Table 2).

Preoperative TAS levels were significantly higher in the TH group compared to those in the control group (1.618±0.253 vs. 1.501±0.232 mmol TroloxEq/L) (p<0.05). Postoperative TOS levels were almost similar in both groups (p>0.05).

Postoperative OSI levels were significantly lower in the TH group compared to those in the control group (14.4±2.9 vs.

16.3±3.7) (p<0.05).

The mean VAS scores measured at 0–24 h and 24–48 h postoperatively were the same in both groups (8/6 vs. 8/6, respectively) (p>0.05). However, mean diclofenac consump-

DISCUSSION TH is known to protect tissues against inflammation through its anti-inflammatory effect. Due to this effect, TH is commonly performed in numerous clinical conditions including traumatic brain injury, spinal cord injury, cardiac arrest, and neonatal hypoxic-ischemic encephalopathy.[20,21] Although the exact mechanism of TH remains unclear, administration of cold compress is known to have an analgesic effect. This effect is considered to arise from several mechanisms including sensory nerve inactivation, reduced nerve conduction velocity, activation of inhibitory interneurons (gate mechanism), and endorphin release.[4,5,22]

Table 1. Comparison of age, gender, primary pathology diagnosis, and wound type between the two groups

Therapeutic hypothermia (n=50)

Control (n=50)

p

Age

52.9±20.5

53.6±18.2

0.869 0.839

Gender

Female

20 (40)

21 (42)

Male

30 (60)

29 (58)

Primary pathology

Gastrointestinal perforation

17 (34)

14 (28)

Intestinal obstructıon

8 (16)

11 (22)

Acute cholecystitis-cholangitis

6 (12)

6 (12)

Incarcerated ventral hernia

5 (10)

3 (6)

Acute appendicitis

3 (6)

4 (8)

Liver/spleen laceration

3 (6)

3 (6)

Strangulated inguinal hernia

3 (6)

3 (6)

Gastrointestinal hemorrhage

2 (4)

3 (6)

Acute necrotizing pancreatitis

2 (4)

2 (4)

Mesenteric ischemia

1 (2)

1 (2)

Wound type

2

14 (28)

13 (26)

3

31 (62)

33 (66)

4

5 (10)

4 (89)

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

0.900

419

Kılıç et al. Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery

Table 2. Comparison of parameters between the groups

TH (n=50)

Size of incision*

Control (n=50)

19.3±3.3

Duration of surgery (min)**

132.5 (55–185)

Total antioxidant status μmol H2O2Eq/L

19.2±3.1 0.852 135 (95–1445)

1.413±0.258

**

Total antioxidant status mmol TroloxEq/L (Postop day 5)* 1.618±0.253

p

0.246

1.389±0.332 0.617 1.501±0.232 0.017

Total oxidant status μmol H2O2Eq/L

25.478 (11.15–38.782)

26.632 (12.15–38.354)

0.918

Total oxidant status mmol TroloxEq/L (Postop day 5)**

23.094 (16.50–39.145)

24.690 (12.467–37.478)

0.182

**

Oxidative stress index (AU) (Postop day 5)*

14.4±2.9

16.3±3.7 0.004

Albumin g/dL*

3.0±0.4

3.1±0.6

0.520

Albumin g/dL (Postop day 5)

2.9 (2.1–4.8)

2.9 (1.5–4.4)

0.504

C-reactive protein mg/L**

98 (25–199)

80 (21–199)

0.094

**

C-reactive protein mg/L (Postop day 5) **

White blood cell count 103/μL** White blood cell count 103/μL (Postop day 5)**

55 (9–149)

64.5 (22–190)

0.093

13.6 (5.5–24.9)

13.8 (5.6–22.6)

0.923

6.1 (3.6–17.3)

5.6 (3.6–17.4)

0.505

Blood loss (mL)**

180 (100–1500)

190 (130–1350)

0.712

Transfusion (u)

4 (3–49)

4 (3–4)

0.892

Pain score 0–24 h**

8 (5–9)

8 (5–9)

1.000

**

Pain score 24–48 h

6 (3–7)

6 (3–7)

1.000

Nonsteroidal anti-inflammatory drugs deliver 0–24 h**

4 (3–5)

4 (3–5)

1.000

Nonsteroidal anti-inflammatory drugs deliver 24–48 h**

2 (1–3)

3 (1–4)

0.010

Opioid deliver 0–24 h**

2 (2–3)

3 (3–4)

<0.001

Opioid deliver 24–48 h**

1 (0–3)

2 (0–3)

0.002

**

Arithmetic mean±standard deviation; **Median (minimum-maximum). TH: Therapeutic hypothermia.

*

Table 3. Comparison of the SSSI pathogens isolated in both groups Pathogen

TH (n=50)

Control (n=50)

p

n %

n %

SSSI

11 22

17 34

<0.05

MRSA

4 8

6 12

<0.05

CoNS

3 6

5 10

Enterococcus species

2

4

3

6

Escherichia coli

2

4

3

6

SSSI: Superficial surgical site infection; TH: Therapeutic hypothermia. MRSA: Methicillin-resistant staphylococcus aureus; CoNS: Coagulase-negative staphylococci.

TH is also known to have a major role in the suppression of neuroapoptosis, reduction of the metabolic rate of neurons, and the inhibition of nitric oxide and reactive oxygen species (ROS).[23] Overproduction of ROS during inflammation leads to an imbalance between ROS production and the antioxidants in the body, thereby leading to tissue degeneration and ultimately to oxidative stress.[24] Moreover, if this imbalance is in favor of oxidative stress, lipid peroxidation occurs, thus leading to apoptosis because of an impairment in the cellular 420

DNA and membrane structure.[25] In the case of antioxidant depletion, however, peroxyl radicals form covalent bonds with each other, thereby causing impairment of membrane functioning and loss of membrane fluidity. In turn, a decrease in membrane potential leads to increased ion permeability, leading to membrane rupture. As a result, the mitochondrial and other organelle contents are released into the cytoplasm, thus causing cell damage/death.[26] Oxidative stress occurs when the tissue damage caused by active oxidants cannot be prevented by the antioxidant mechanism. In addition, oxidative stress triggers protein denaturation, DNA damage, and lipid peroxidation, thus leading to impairment in the metabolic activity.[27,28] TOS and TAS are commonly measured to predict the total oxidant/antioxidant status of the body.[17,18] In particular, TAS is used for estimating the activity of antioxidants in serum.[29] To determine the status of oxidative stress, OSI is calculated based on the TOS and TAS levels.[23,30] In this study, we also calculated OSI to determine the status of inflammatory responses for each patient. Although TH led to no change in the TOS levels, it resulted in a significant increase in the TAS levels and a decrease in the OSI levels.

This finding suggests that the ROS in inflammatory tissues Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Kılıç et al. Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery

are eliminated more effectively, implicating that the extent of tissue damage in patients undergoing TH is relatively lower, and thus, these patients require less analgesics compared to patients not receiving TH. Risk factors of SSIs include presence of a pre-existing infection, inadequate skin preparation, hair removal and antibiotic choice, administration, and duration.[19] Intraoperative risk factors of SSIs include duration of surgery, blood transfusion, maintenance of asepsis, poor-quality surgical hand scrubbing and gloving, hypothermia, and poor glycemic control.[31] SSSI typically occurs within the first 5 days after surgical procedure. Common laboratory parameters for infection include WBC, CRP, and albumin levels.[32] To prevent SSSI, preoperative antibiotic prophylaxis should be performed, and a second dosage should be administered in surgeries lasting more than 2 h.[33] Most common pathogens causing SSSI include MRSA, CoNS, enterococci, and Escherichia coli.[34] TH decreases the concentration of pro-inflammatory mediators while increasing the release of anti-inflammatory mediators and preventing leukocyte migration.[11–13] In our study, the risk factors for SSSI and the pathogens isolated from surgical site infections were similar to those reported in the literature. To determine the status of inflammatory responses, we measured the TAS, TOS, and OSI levels in addition to the WBC, CRP, and albumin levels. SSSI was less common in the TH group. Moreover, serum WBC and CRP levels were slightly lower in the TH group compared to those in the control group, although no significant difference was found in the albumin levels between the two groups. We consider that this effect of TH arises from elevated TAS levels because increased antioxidant activity not only prevents excessive leukocyte migration but also eliminates the ROS more effectively, thereby preventing the formation of ischemic and necrotic tissues that establish a favorable local environment for bacterial proliferation.

In conclusion, in patients undergoing emergency open abdominal surgery, TH led to lower requirement for analgesics and lower SSSI rates in the early postoperative period. We consider that TH exerts this effect by elevating the TAS level, eliminating ROS, and decreasing the effects of inflammatory mediators. Nevertheless, further studies are needed to provide more substantial findings related to the role of TH in the prevention or reduction of postoperative pain and SSSI. Conflict of interest: None declared.

REFERENCES 1. Trescot AM. Cryoanalgesia in interventional pain management. Pain Physician 2003;6:345–60.

2. Saeliw P, Preechawai P, Aui-aree N. Evaluating the effects of ice application on patient comfort before and after botulinum toxin type A injections. J Med Assoc Thai 2010;93:1200–4.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

3. Taghizadeh F, Ellison T, Traylor-Knowles M. Evaluation of pain associated with facial injections using CoolSkin in rhytidectomy. J Pain Res 2011;4:309–13.

4. Algafly AA, George KP. The effect of cryotherapy on nerve conduction velocity, pain threshold and pain tolerance. Br J Sports Med 2007;41:365– 9.

5. Herrera E, Sandoval MC, Camargo DM, Salvini TF. Motor and sensory nerve conduction are affected differently by ice pack, ice massage, and cold water immersion. Phys Ther 2010;90:581–91.

6. McMeeken J, Lewis MM, Cocks S. Effects of cooling with simulated ice on skin temperature and nerve conduction velocity. Aust J Physiother 1984;30:111–4.

7. Zachariassen KE. Hypothermia and cellular physiology. Arctic Med Res 1991;50 Suppl 6:13–7.

8. Centers for Disease Control and Prevention (CDC). Surgical Site Infection (SSI) Event. Atlanta: CDC; 2013. Available at: http://www.cdc. gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf. Accessed Sept 13, 2018.

9. Ott E, Saathoff S, Graf K, Schwab F, Chaberny IF. The prevalence of nosocomial and community acquired infections in a university hospital: an observational study. Dtsch Arztebl Int 2013;110:533–40.

10. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, American Society of Health-System Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013;70:195–283.

11. Lim CM, Kim MS, Ahn JJ, Kim MJ, Kwon Y, Lee I, et al. Hypothermia protects against endotoxin-induced acute lung injury in rats. Intensive Care Med 2003;29:453–9.

12. Fujimoto K, Fujita M, Tsuruta R, Tanaka R, Shinagawa H, Izumi T, et al. Early induction of moderate hypothermia suppresses systemic inflammatory cytokines and intracellular adhesion molecule-1 in rats with caerulein-induced pancreatitis and endotoxemia. Pancreas 2008;37:176– 81.

13. Lee SL, Battistella FD, Go K. Hypothermia induces T-cell production of immunosuppressive cytokines. J Surg Res 2001;100:150–3.

14. Meybohm P, Gruenewald M, Zacharowski KD, Albrecht M, Lucius R, Fösel N, et al. Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation. Crit Care 2010;14:R21.

15. Johnson M, Haddix T, Pohlman T, Verrier ED. Hypothermia reversibly inhibits endothelial cell expression of E-selectin and tissue factor. J Card Surg 1995;10:428–35.

16. Hanusch C, Nowak K, Gill IS, Törlitz P, Rafat N, Mueller AM, et al.

Hypothermic preservation of lung allograft inhibits cytokine-induced chemoattractant-1, endothelial leucocyte adhesion molecule, vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 expression.

Clin Exp Immunol 2007;149:364–71.

17. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–11.

18. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation.

Clin Biochem 2004;37:277–85.

19. National Healthcare Safety Network. Surgical Site Infection (SSI) Event. Atlanta, GA: Centers for Disease Control and Prevention; 2013.

20. Dietrich WD 3rd.Therapeutic hypothermia for spinal cord injury. Crit Care Med 2009;37:S238–42.

21. Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an up-

421

Kılıç et al. Effect of therapeutic hypothermia on superficial surgical site infection and postoperative pain in urgent abdominal surgery dated systematic review and meta-analysis. Arch Pediatr Adolesc Med 2012;166:558–66.

22. Zencir G, Eser I. Effects of Cold Therapy on Pain and Breathing Exercises Among Median Sternotomy Patients. Pain Manag Nurs 2016;17:401– 10.

23. Edwards AD, Yue X, Squier MV, Thoresen M, Cady EB, Penrice J, et al. Specific inhibition of apoptosis after cerebral hypoxia-ischaemia by moderate post-insult hypothermia. Biochem Biophys Res Commun 1995;217:1193–9.

28. Katsoulis K, Kontakiotis T, Baltopoulos G, Kotsovili A, Legakis IN. Total antioxidant status and severity of community-acquired pneumonia: are they correlated? Respiration 2005;72:381–7.

29. LeBel CP, Bondy SC. Oxygen radicals: common mediators of neurotoxicity. Neurotoxicol Teratol 1991;13:341–6.

30. Serafini M, Del Rio D. Understanding the association between dietary antioxidants, redox status and disease: is the Total Antioxidant Capacity the right tool? Redox Rep 2004;9:145–52.

24. Halliwell B, Aruoma OI. DNA damage by oxygen-derived species.

Its mechanism and measurement in mammalian systems. FEBS Lett 1991;281:9–19.

31. Anderson DJ, Podgorny K, Berríos-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35:605– 27.

25. Atlan N, Sepici Dinçel A, Koca C. Diabetes Mellitus and Oxidative Stress. Turk J Biochem 2006;31;51–6.

32. Kılıç YA, Abbasoğlu O. Surgical site infections: Introduction and definitions. Hospital Infection Journal 2001;5:63–8.

26. Catalá A. An overview of lipid peroxidation with emphasis in outer segments of photoreceptors and the chemiluminescence assay. Int J Biochem Cell Biol 2006;38:1482–95.

33. Ban KA, Minei JP, Laronga C, Harbrecht BG, Jensen EH, Fry DE, et al.

American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg 2017;224:59–74.

27. Duracková Z. Some current insights into oxidative stress. Physiol Res 2010;59:459–69.

34. Owens CD, Stoessel K. Surgical site infections: epidemiology, microbiology and prevention. J Hosp Infect 2008;70 Suppl 2:3–10.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Acil abdominal cerrahi geçiren hastalarda yüzeyel cerrahi alan enfeksiyonu ve ameliyat sonrası ağrıya terapötik hipoterminin etkisi Dr. Erol Kılıç, Dr. Mustafa Uğur Mustafa Kemal Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Hatay

AMAÇ: Terapotik hipoterminin, elektif cerrahi uygulanan hastalarda yara yeri enfeksiyonu ve ameliyat sonrası ağrıya etkili olduğu bilinse de, acil laparatomi uygulanan hastalardaki etkisi net bilinmemektedir. Çalışmada hipotezimiz terapotik hipoterminin açık acil abdominal cerrahi uygulanan hastalarda yüzeyel cerrahi alan enfeksiyonu ve ameliyat sonrası ağrıyı azaltacağıdır.

GEREÇ VE YÖNTEM: 2016–2017 tarihleri arasında acil abdominal cerrahi uygulanan hastalar bilgisayar aracılığıyla randomize edilerek hastaların yarısına ameliyat sonrası birinci saat içinde steril buz kompres ile lokal soğutma, diğer yarısına klasik steril kompres uygulanarak gruplandırıldı.

Grupların yaş, cinsiyet, primer tanı, kesi boyutu, yara tipi, boyutu ve cerrahi süre belirlenerek karşılaştırıldı. Ameliyat sonrası 48 saat boyunca her üç saatte bir vizüel ağrı skorları ile bu dönemlerdeki analjezik gereksinimi belirlenerek gruplar karşılaştırıldı. Tüm hastalardan ameliyat öncesi ve sonrası beşinci günde kan alınarak, C-reaktif protein, beyaz küre, albumin, serum total antioksidan status, total oksidan status seviyeleri ölçüldü, oksidatif stres indeksi hesaplanarak gruplar karşılaştırıldı. Gruplarda gelişen yüzeyel cerrahi alan enfeksiyonu karşılaştırıldı.

BULGULAR: Gruplar arasında yaş, cinsiyet, primer tanı, kesi boyutu, yara tipi, boyutu ve cerrahi süre açısından anlamlı fark yoktu (p>0.05). Gruplar arasında vizüel ağrı skorları açısından istatiksel açıdan anlamlı fark olmamakla birlikte (p>0.05) steril buz kompres uygulanan grupta analjezik ihtiyacı daha azdı (p<0.05). Ameliyat öncesi lökosit sayısı, albumin, C-reaktif protein, serum total antioksidan status, total oksidan status ve oksidatif stres indeksi açısından fark yoktu (p>0.05). Ameliyat sonrası beşinci günde gruplar arasında serum total antioksidan status düzeyi steril buz kompres uygulanan grupta belirgin olarak artmıştı ve oksidatif stres indeksi belirgin olarak azalmıştı (p<0.05). Yüzeyel cerrahi alan enfeksiyonu steril buz kompres uygulanan grupta belirgin olarak daha azdı (p<0.05).

TARTIŞMA: Terapotik hipotermi/lokal soğutma, acil açık abdominal cerrahi uygulanan hastalarda ameliyat sonrası dönemde analjezik ihtiyacını azaltmaktadır. Ayrıca yüzeyel cerrahi alan enfeksiyonunun gelişmesini önlemektedir. Bu etkileri serum total antioksidan status seviyesini arttırarak oksidatif stres indeksini azaltarak gerçekleştirmektedir.

Anahtar sözcükler: Ameliyat sonrası ağrı; terapotik hipotermi; yara yeri enfeksiyonu.

Ulus Travma Acil Cerrahi Derg 2018;24(5):417-422

422

doi: 10.5505/tjtes.2018.23345

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

ORIG I N A L A R T IC L E

Significance of hemogram on diagnosis of acute appendicitis during pregnancy Hamza Çınar, M.D.,1 Çağrı Akalın, M.D.,1

Ali Aygün, M.D.,2 Murat Derebey, M.D.,3 İsmail Alper Tarım, M.D.,4 Sercan Büyükakıncak, M.D.,5 Kenan Erzurumlu, M.D.4

1

Department of General Surgery, Ordu University Faculty of Medicine, Ordu-Turkey

2

Department of Emergency Medicine, Ordu University Faculty of Medicine, Ordu-Turkey

3

Department of General Surgery, Tatvan State Hospital, Bitlis-Turkey

4

Department of General Surgery, Ondokuz Mayıs University Faculty of Medicine, Samsun-Turkey

5

Department of General Surgery, Akçaabat Haçkalı Baba State Hospital, Trabzon-Turkey

ABSTRACT BACKGROUND: Acute appendicitis (AA) is the most common emergency surgical condition during pregnancy after obstetric and gynecological pathologies. Urgent and accurate diagnosis of AA in pregnant patients reduces maternal and fetal morbidity/mortality rates. This study evaluated the significance of hemogram to diagnose AA during pregnancy.

METHODS: Forty-seven pregnant patients operated for AA in the Ordu or Ondokuz Mayis University Medical School Hospitals between January 2007 and December 2017 were compared with 47 healthy pregnant women in terms of hemogram parameters, including the white blood cell (WBC) count, neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and red cell distribution width (RDW) values. The operated group was evaluated based on post-operative pathologic results and subclassified into appendicitis positive (Group A) and appendicitis negative (Group B) groups. The subgroups were compared to the control group.

RESULTS: The WBC and neutrophil count and mean NLR and PLR values were significantly higher in Group A compared to Group B and the control group (p<0.001). The mean lymphocyte count was significantly lower in Group A compared to other groups (p<0.001).

The MPV and RDW values and mean platelet count showed no significant difference between groups (p>0.05). When cutoff values for WBC, neutrophil count, NLR, PLR, and lymphocyte counts were set to >10300, >7950, >5.50, >155.2, and ≤1330, respectively, the sensitivity rates were 72.5%, 80%, 90%, 77.5% and 85%, whereas specificity rates were 72.3%, 79.7%, 89.4%, 74.5%, and 82.5%, respectively.

CONCLUSION: When comparing pregnant women diagnosed with AA to patients operated for suspected AA and healthy pregnant women, the WBC and neutrophil count and NLR and PLR values were found to be significantly higher, whereas lymphocyte counts were lower. In addition to medical history, physical examination and imaging techniques, hemogram parameters should be considered to diagnose AA in pregnant women.

Keywords: Appendicitis; diagnosis; hemogram; lymphocyte; neutrophil; pregnancy.

INTRODUCTION Acute appendicitis (AA) is the most common surgical pathology diagnosed in patients admitted to emergency departments with abdominal pain.[1] AA is among the most common

indications for emergency surgery during pregnancy after obstetric and gynecological pathologies. The incidence of AA is 1 in 500–2000 pregnant women.[2,3] AA occurs mostly during the second trimester, although it can be seen at any time during pregnancy.[4] The urgent and accurate diagnosis

Cite this article as: Çınar H, Aygün A, Derebey M, Tarım İA, Akalın Ç, Büyükakıncak S, et al. Significance of hemogram on diagnosis of acute appendicitis during pregnancy. Ulus Travma Acil Cerrahi Derg 2018;24:423-428.

Address for correspondence: Hamza Çınar, M.D. Ordu Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Altınordu, 52100 Ordu, Turkey Tel: +90 452 - 226 52 14 E-mail: drhamzacinar@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):423-428 DOI: 10.5505/tjtes.2018.62753 Submitted: 20.05.2018 Accepted: 14.08.2018 Online: 28.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

423

Çınar et al. Significance of hemogram on diagnosis of acute appendicitis during pregnancy

of AA is essential for preventing potential complications for the mother and/or fetus. Symptoms including nausea, vomiting, and anorexia are usually seen in the early period of pregnancy and also in AA; therefore, the diagnosis of this condition is challenging for clinicians. Physiological increases in the leucocyte count and C-reactive protein (CRP) levels may be observed during pregnancy. Tomography is avoided in pregnant women to protect the fetus from ionized radiation.

The preferred imaging techniques are ultrasonography and/ or magnetic resonance imaging.[5,6] Considering these factors, diagnosing AA during pregnancy can be challenging for physicians, and therefore, the diagnosis can be delayed.

Hemogram parameters including the white blood cell (WBC) count, neutrophil count, lymphocyte count, neutrophil-tolymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) are inflammatory markers.

The changing levels of these parameters are measured in several inflammatory pathologies.[7] It is extremely important to diagnose suspected AA early in pregnant women and to avoid unnecessary surgery. The aim of this study is to determine the hemogram parameters, which are readily available and are evaluated in emergency conditions as a diagnostic tool in diagnosis of AA during pregnancy.

MATERIALS AND METHODS The study included 47 pregnant patients who were operated for suspected AA and 47 healthy pregnant women between January 2007 and December 2017 at Medical School Hospitals of the Ordu or Ondokuz Mayis University. The hemogram parameters including the WBC, neutrophil count, lymphocyte count, platelet count, NLR, PLR, MPV, and red cell distribution width (RDW) values were retrospectively examined from the medical records of the patients. The post-operative pathological results of appendix specimens were also investigated. All patients with a final pathological evaluation reported as acute focal appendicitis, acute suppurated appendicitis, acute perforated appendicitis, and acute gangrenous appendicitis were included in the AA group (Group A), whereas patients with a normal histopathology were included in the non-appendicitis group (Group B). Forty-seven healthy pregnant women who were under routine pregnancy followup during the same period at the obstetrics clinics of the same hospitals were included as the control group. Exclusion criteria were the presence of hematological diseases, chronic renal failure, chronic liver disease, chronic obstructive lung disease, asthma, autoimmune diseases, cancer, rheumatoid arthritis, bacterial, viral or parasitic infection, immune deficiency, alcohol or tobacco use, and missing records. The age, gestational age, time to diagnosis, length of hospitalization, type of surgical incision, WBC, neutrophil, lymphocyte, and platelet count, and the NLR, PLR, MPV, and RDW values for each patient were recorded. The study was approved by the Ethics Committee of the Ordu University.

424

All tests were performed on blood samples obtained via venous system and collected into ethylene diamine tetra acetic acid tubes. Hemograms that were taken within 24 hours prior to surgery were accepted for the AA group. The WBC, neutrophil, platelet, and lymphocyte counts, and the MPV and RDW values were analyzed via hemogram samples. The NLR and PLR values were calculated by dividing neutrophil and platelet counts to lymphocyte count. Hematological parameters were measured by an automated hematology analyzer (Abbott Cell-Dyn 3700 Hematology Analyzer, Abbott Diagnostics, USA). The upper limits of the reference intervals were as follows: leukocyte counts (WBC); 4600–10200 /µL, platelet; 142–424 × 10³/μL; neutrophil; 2–6.9 × 10³/μL; lymphocyte; 0.6–3.4 × 10³/μL, MPV; 0–99.9fL; and RDW; 0%–16.2%.

Statistical Analysis Statistical analysis was performed using the SPSS 22.0 software (IBM Corporation, Armonk, NY, USA). The Shapiro– Wilk test was used to determine the compliance of data to a normal distribution, and the Levene test was used to determine the homogeneity of variances among the groups.

The independent samples T test with bootstrap results was used to compare two independent groups, whereas the Mann–Whitney U test was used with the Monte Carlo simulation technique. One-way analysis of variance (robust test: Browne–Forsythe) was used together with bootstrap results to compare more than two groups with other groups.

The Kruskal–Wallis H test, least significant differences, and Games–Howell tests were used for post-hoc analysis. The correlation between classification of the patient groups separated by cutoff values was calculated according to the variables, and real classification was expressed by examination of sensitivity and specificity using the receiver operating characteristic (ROC) curve analysis. Quantitative data are expressed as the mean±standard deviation, median-interquartile range, or median and range (maximum–minimum). Categorical data are expressed as n (number) or percentage (%) and analyzed

by Fisher’s exact test.

RESULTS All the patients who underwent surgery were divided into two groups based on their pathology results; Group A consisted of 40 patients (85.1%) with AA and Group B with 7 (14.9%) patients without appendicitis. There was no significant difference between groups in terms of age, time period of admission to diagnosis, or the length of post-operative hospitalization (p>0.05). Of 40 patients in Group A, 16 (40%), 20 (50%), and 4 (10%) were in the 1st, 2nd, and 3rd trimester of pregnancy, respectively, whereas in Group B, 4 (57.1%) and 3 (42.9%) were in the 1st and 2nd trimester of pregnancy, respectively. The control group consisted of 15 (31.9%), 17 (36.1%), and 15 (31.9%) subjects in the 1st, 2nd, and 3rd trimester of pregnancy, respectively. No significant difference was found Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Çınar et al. Significance of hemogram on diagnosis of acute appendicitis during pregnancy

Group B and the control group (p<0.001). The mean lymphocyte count was significantly lower in Group A compared to other groups (p<0.001). There was no significant difference between groups in terms of the mean MPV and RDW values and platelet count (p>0.05) (Table 1).

between Group A and Group B for gestational age (p>0.05).

Laparotomy was performed in all patients using McBurney’s or right paramedian incisions. In pregnant women diagnosed with AA, McBurney’s incision was mostly preferred (78.7%).

Paramedian incision was preferred in patients with older gestational age. The mean post-operative length of hospitalization was 4.18±3.09 days in Group A and 3.57±1.39 days in Group B, and no significant difference was found between the groups in terms of length of hospitalization (p>0.05). A significantly higher WBC and neutrophil counts and the mean NLR and PLR values were detected in Group A compared to

The ROC curve analysis was performed to evaluate the predictive ability of hemogram parameters to diagnose AA in pregnant women. Sensitivity, specificity, and accuracy rate values for hemogram parameters were estimated based on cutoff values determined by ROC analyses (Table 2).

Table 1. Comparison of groups for age, gestational age, time to diagnosis with symptoms, surgical incision, and hemogram parameters

Group A (n=40)

Group B (n=7)

Control Group (n=47)

p

Age

27.0±5.55

25.14±5.08

29.74±6.13

0.36

Gestational age (weeks)

16.88±7.72

13.0±4.89

21.60±9.77

0.009

Time to diagnosis with symptoms (hours)

23.28±21.20

12.0±7.97

–

0.175 0.630

Surgical incision type

Paramedian

20% (n=8)

28.57% (n=2)

–

McBurney

80% (n=32)

71.42 (n=5)

–

4.18±3.09

3.57±1.39

–

Post-operative hospital stay (days)

0.617

White blood cells (K/μL) 12886±4785 13194±3520 9063±1869 <0.001 *

a

a

b

Mean platelet volume* (fL)

8.03±1.22 7.56±1.27 7.51±0.90 0.07

Red cell distribution width (%)

14.83±2.18 14.78±1.26 14.23±1.26 0.255

*

Neutrophil count (K/μL)* 11198±4624a 10967±3550a 6561±1616b <0.001 Lymphocyte count (K/μL)* 1093±442c 1415±413b 1845±641a <0.001 Neutrophil-to-lymphocyte ratio** Platelet-to-lymphocyte ratio** Platelet count (K/μL)

*

12.10 (2.28–37.10)a

7.70 (3.40–13.60)b

218.91 (93.10–735.13)a

190.80 (93.10–289.60)a,b

3.57 (1.22–28.90)c <0.001 130.30 (58.65–429.03)b <0.001

229125±74976 261000±74446 238276±67148 0.528

Indicate inter-group differences within the row Mann-Whitney U test (Monte Carlo)–one-way analysis of variance (Browne–Forsythe)–(Bootstrap) Post-hoc test: least significant difference—Games–Howell Kruskal–Wallis test Post-hoc test (Monte Carlo): nonparametric post-hoc test (Miller, 1966) * Mean±standard deviation; **Median; (range, maximum–minimum). a,b,c

Table 2. Sensitivity and specificity rates for hemogram parameters based on cut-off values in pregnant women diagnosed with AA

Hemogram parameters (cut-off values)

Sensitivity (%)

Specificity (%)

Accuracy rate (%)

AUC±SE

>10300

72.5

72.3

72.4

0.815±0.046

Mean platelet volume

>7.65

62.5

60.6

60.9

0.648±0.063

Red cell distribution width

>14.2

57.5

53.2

55.1

0.552±0.063

Neutrophil count (K/mL)

>7950

80.0

79.7

81.6

0.880±0.038

Lymphocyte count (K/mL)

<1330

85

82.5

85.0

0.864±0.042

>225000

57.4

47.5

50.5

0.536±0.063

>5.50

90.0

89.4

90.8

0.920±0.034

>155.20

77.5

74.5

75.8

0.795±0.050

White blood cells (K/mL)

Platelet count (K/mL) Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyte ratio

ROC curve analysis (Youden index J—Honley and McNell). AA: Acute appendicitis; AUC: Area under the receiver operating characteristic curve, SE: Standard error.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

425

Çınar et al. Significance of hemogram on diagnosis of acute appendicitis during pregnancy

To predict AA, the sensitivity and specificity values for various hemogram parameters at set cutoff values were as follows: for WBC; 72.5% sensitivity and 72.3% specificity at cutoff >10300 cells/mL, for neutrophil count; 80% sensitivity and 79.7% specificity at cutoff >7950 cells/ mL, for lymphocyte count; <1330 cells/mL had 85% sensitivity and 82.5% specificity, for NLR; 90% sensitivity and 89.4% specificity at cutoff >5.50, for PLR; 77.5% sensitivity and 74.5% specificity at cutoff >155.2, for platelet count; 57.4% sensitivity and 47.5% specificity at cutoff >225000 cells/mL; for RDW, 57.5% sensitivity and 53.2% specificity at cutoff >14.2; and for MPV; 62.5% sensitivity and 60.6% specificity at cutoff >7.65.

DISCUSSION Diagnosis of AA in pregnant patients is more difficult compared to non-pregnant patients due to anatomical and physiological changes in pregnancy. Physiological features of pregnancy such as anorexia, nausea, and vomiting can mask AA symptoms. Uterus enlargement and reduced tonus of abdominal muscles causes uterus growing into the abdomen and the appendix displacement as well.[8] The utilization of radiological imaging techniques is limited in pregnant patients for the goal of fetus protection. Therefore, it is difficult to diagnose AA by history and physical examination. Delay in diagnosis increases the risk of appendix perforation. Perforation leads to peritonitis and sepsis, which causes increased mortality and morbidity rates for the mother and baby.[8–10] Babaknia et al.[11] have reported that the rate of fetal loss was 1.5% in non-perforated and 35.7% in perforated AA patients. The incidence of perforated appendicitis during pregnancy depends on the time between the onset of symptoms and surgical intervention, and the risk for perforation is increased by over 20 hours.[12] It is extremely important to confirm early diagnosis in pregnant patients with suspected AA. Although diagnosis should be confirmed urgently, negative appendectomy should be avoided as well. Negative appendectomy rates during pregnancy have been reported to range between 3% and 23%.[13,14] The rate of negative appendectomy was 14.9% in our study.

Hemogram is a readily available and valuable test, and it plays an essential role in diagnosis of AA. Among the hemogram parameters, the WBC, neutrophil, and lymphocyte counts and NLR, PLR, and MPV act as inflammatory markers. The predictive value of these markers for AA is currently becoming more promising.[5,15,16] Leucocytosis is commonly observed in patients with AA. In our study, the WBC count of pregnant AA patients was found to be 12886±4785 mm3, and there was a significant difference compared to healthy pregnant women (p<0.001). Estimated sensitivity and specificity values for WBC with a cutoff value >10300 were 72.5% and 72.3%, respectively. Despite the mentioned sensitivity and specificity rates, the WBC count can increase up to 18.000–30.000 mm3 at a period closer to delivery.[8] Therefore, the WBC count alone may be used as a specific predictor of AA during preg426

nancy. WBC should be used in combination with parameters such as the neutrophil and lymphocyte counts and NLR and PLR with higher sensitivity and specificity values.[5] In several inflammatory diseases, regular response of circulating leukocytes is an increased level of neutrophil and reduced level of lymphocyte counts.[17] AA is an inflammatory disease; therefore, a high neutrophil count and low lymphocyte count should be expected. Thus, in our study, the mean neutrophil count was higher and mean lymphocyte count was lower in the appendicitis group compared to other groups (p<0.001).

Based on cutoff values, neutrophil and lymphocyte counts showed 80% and 85% sensitivity and 79.7% and 82.5% specificity, respectively. In the study by Yazar et al.,[5] high neutrophil and low lymphocyte values were found in pregnant patients with appendicitis. Recently, several studies suggested that an increased NLR or PLR could be better predictors of AA compared to CRP, WBC, or the neutrophil count alone.

[5,18,19] A recent study by Yazar et al.[5] including 28 pregnant women with AA found 78.6% and 100% sensitivity and 80% and 42.9% specificity, based on cutoff values for NLR and PLR, respectively. Additionally, they have reported accurate diagnosis of AA with a 90.5% rate when NLR and PLR were combined with the WBC count, CRP level, and lymphocyte count. Similarly to previous studies, our study showed that NLR and PLR, based on cutoff values, have 90% and 77.5% sensitivity and 89.4% and 74.5% specificity, respectively.

Among the hemogram parameters, a higher sensitivity and specificity were observed for NLR in terms of AA diagnosis in pregnant women.

MPV is the most common marker for the production and functional status of platelet, and it reflects inflammatory burden. There are several studies that indicate that MPV values are useful in diagnosing AA. Narci et al.[20] have suggested that high MPV values can be used for the diagnosis of AA. In another study, Albayrak et al.[21] found a significantly lower MPV level in patients with AA compared to the control group. Similarly, no difference was found between the groups in a study

by Yazıcı et al.,[5] which compared platelet counts in pregnant women. However, in our study, there was no significant difference in MPV values between pregnant women diagnosed with AA and the control group (p>0.05). The predictive value of RDW has been evaluated in several studies among patients with appendicitis; however these studies have concluded with controversial results.[22–24] To the best of our knowledge, ours is the first study to evaluate a predictive value of RDW levels to diagnose AA during pregnancy. We could not demonstrate a significant predictive value of RDW in our study.

Conclusion In pregnant patients with suspected AA, a more urgent and accurate diagnosis can be achieved using the WBC, neutrophil, and lymphocyte counts and NLR and PLR values in combination with medical history, physical examination, and Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Çınar et al. Significance of hemogram on diagnosis of acute appendicitis during pregnancy

imaging techniques. As a result, maternal and fetal morbidity/ mortality rates can be reduced and negative laparotomy rates can be minimized. Our results can contribute to the limited literature available on AA in pregnant women.

11. Babaknia A, Parsa H, Woodruff JD. Appendicitis during pregnancy. Obstet Gynecol 1977;50:40–4.

Limitation of the study: Retrospective design based on analyses of patient records and a relatively small sample size.

12. Yilmaz HG, Akgun Y, Bac B, Celik Y. Acute appendicitis in pregnancyrisk factors associated with principal outcomes: a case control study. Int J Surg 2007;5:192–7.

Conflict of interest: None declared.

REFERENCES 1. Demircan A, Aygencel G, Karamercan M, Ergin M, Yilmaz TU, Karamercan A. Ultrasonographic findings and evaluation of white blood cell counts in patients undergoing laparotomy with the diagnosis of acute appendicitis [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2010;16:248–52.

2. Andersen B, Nielsen TF. Appendicitis in pregnancy: diagnosis, management and complications. Acta Obstet Gynecol Scand 1999;78:758–62.

3. Arer İM, Alemdaroğlu S, Yeşilağaç H, Yabanoğlu H. Acute appendicitis during pregnancy: case series of 20 pregnant women. Ulus Travma Acil Cerrahi Derg 2016;22:545–8.

4. Onder A, Kapan M, Arikanoglu Z, Sak ME, Gumus M, Taskesen F, et al.

Acute Appendicits in Pregnancy: Evaluation of 129 Patients During 20 years. J Curr Surg 2012;2:4–10.

5. Yazar FM, Bakacak M, Emre A, Urfalıoglu A, Serin S, Cengiz E, et al.

Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy. Kaohsiung J Med Sci 2015;31:591–6.

6. Franca Neto AH, Amorim MM, Nóbrega BM. Acute appendicitis in pregnancy: literature review. Rev Assoc Med Bras (1992) 2015;61:170– 7.

7. Acar E, Özcan Ö, Deliktaş H, Beydilli H, Kırlı İ, Alatas ÖD, et al. Laboratory markers has many valuable parameters in the discrimination between acute appendicitis and renal colic. Ulus Travma Acil Cerrahi Derg 2016;22:17–22.

8. Jung SJ, Lee DK, Kim JH, Kong PS, Kim KH, Bae SW. Appendicitis during Pregnancy: The Clinical Experience of a Secondary Hospital. J Korean Soc Coloproctol 2012;28:152–9.

9. Bickell NA, Aufses AH Jr, Rojas M, Bodian C. How time affects the risk of rupture in appendicitis. J Am Coll Surg 2006;202:401–6.

10. Al-Qudah MS, Amr M, Sroujieh A, Issa A. Appendectomy in pregnancy:

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

the experience of a university hospital. J Obstet Gynaecol 1999;19:362– 4.

13. McGee TM. Acute appendicitis in pregnancy. Aust N Z J Obstet Gynaecol 1989;29:378–85.

14. McGory ML, Zingmond DS, Tillou A, Hiatt JR, Ko CY, Cryer HM. Negative appendectomy in pregnant women is associated with a substantial risk of fetal loss. J Am Coll Surg 2007;205:534–40.

15. Peng W, Li C, Wen TF, Yan LN, Li B, Wang WT, et al. Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival.

J Surg Res 2014;192:402–8.

16. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 2013;11:55–9.

17. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102:5–14.

18. Markar SR, Karthikesalingam A, Falzon A, Kan Y. The diagnostic value of neutrophil: lymphocyte ratio in adults with suspected acute appendicitis. Acta Chir Belg 2010;110:543–7.

19. Goodman DA, Goodman CB, Monk JS. Use of the neutrophil:lymphocyte ratio in the diagnosis of appendicitis. Am Surg 1995;61:257–9.

20. Narci H, Turk E, Karagulle E, Togan T, Karabulut K. The Role of Mean Platelet Volume in the Diagnosis of Acute Appendicitis: A Retrospective Case-Controlled Study. Iran Red Crescent Med J 2013;15:e11934.

21. Albayrak Y, Albayrak A, Albayrak F, Yildirim R, Aylu B, Uyanik A, et al.

Mean Platelet Volume: A New Predictor in Confirming Acute Appendicitis Diagnosis. Clin Appl Thromb Hemost 2011;17:362–6.

22. Narci H, Turk E, Karagulle E, Togan T, Karabulut K. The role of red cell distribution width in the diagnosis of acute appendicitis: a retrospective case-controlled study. World J Emerg Surg 2013;8:46.

23. Tanrikulu CS, Tanrikulu Y, Sabuncuoglu MZ, Karamercan. MA, Akkapulu N, Coskun F. Mean platelet volume and red cell distribution width as a diagnostic marker in acute appendicitis. Iran Red Crescent Med J 2014;16:e10211.

24. Ertekin B, Hasan K, Erdemir E, Doğan E, Acar T, Demir LS. Efficacy of Use of Red Cell Distribution Width as a Diagnostic Marker in Acute Appendicitis. Eurasian J Emerg Med 2017;16:29–33.

427

Çınar et al. Significance of hemogram on diagnosis of acute appendicitis during pregnancy

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Gebelikte hemogramın akut apandisit tanısındaki önemi Dr. Hamza Çınar,1 Dr. Ali Aygun,2 Dr. Murat Derebey,3 Dr. İsmail Alper Tarım,4 Dr. Çağrı Akalın,1 Dr. Sercan Büyükakıncak,5 Dr. Kenan Erzurumlu4 Ordu Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ordu Ordu Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Ordu 3 Tatvan Devlet Hastanesi, Genel Cerrahi Kliniği, Bitlis 4 Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Samsun 5 Akçaabat Haçkalı Baba Devlet Hastanesi, Genel Cerrahi Kliniği, Trabzon 1 2

AMAÇ: Akut apandisit (AA) gebelik döneminde obstetrik ve jinekolojik patolojilerden sonra en sık acil cerrahi gerektiren durumdur. Gebe hastalarda AA tanısının hızlı ve doğru konulması maternal ve fetal morbite/mortalite oranlarını azaltır. Bu çalışma, hemogramın gebelik döneminde AA tanısı koymadaki önemini irdelemektedir.

GEREÇ VE YÖNTEM: Ordu veya Ondokuz Mayıs Üniversitesi Tıp Fakültesi Hastanesi’nde Ocak 2007–Aralık 2017 yılları arasında AA nedeniyle ameliyat edilen 47 gebe hasta ile 47 sağlıklı gebe hastanın hemogram parametrelerinden beyaz kan hücresi (WBC) sayısı, nötrofil sayısı, lenfosit sayısı, platelet sayısı, nötrofil/lenfosit oranı (NLO), platelet/lenfosit oranı (PLO), mean platelet volüm (MPV) ve kırmızı hücre dağıtım genişliği (RDW) değerleri kıyaslandı. Ameliyat edilen hastalar, patoloji sonucu apandisit olanlar Grup A normal olanlar ise Grup B olarak ikiye ayrıldı ve kontrol grubu ile kıyaslandı.

BULGULAR: Grup A hastalarının WBC sayısı, nötrofil sayısı, ortalama NLO ve PLO değerleri Grup B ve kontrol hastalarından anlamlı olarak yüksek tespit edildi (p<0.001). Lenfosit sayısı ortalamasının Grup A hastalarında diğer gruplardan anlamlı olarak düşük olduğu görüldü (p<0.001). MPV, RDW ve ortalama platelet sayısı açısından gruplar arasında anlamlı bir farklılık yoktu (p>0.05). WBC sayısı, nötrofil sayısı, NLO, PLO ve lenfosit sayısı için kestirim değerleri sırasıyla >10300, >7950, >5.50, >155.2 ve ≤1330 olarak alındığında sensivite oranları sırasıyla %72.5, %80, %90, %77.5 ve %85 olarak gözlenirken spesifite oranları ise sırasıyla %72.3, %79.7, %89.4, %74.5 ve %82.5 olarak tespit edildi.

TARTIŞMA: Akut apandisit tanısı olan gebe kadınlarda WBC sayısı, nötrofil sayısı, NLO ve PLO değerleri kontrol grubu ve apandisit şüphesi nedeniyle ameliyat edilen hastalardan istatistiksel olarak anlamlı olacak şekilde yüksek bulunurken lenfosit sayısı ise düşük bulunmuştur. Gebe kadınlarda AA tanısı koymak için anamnez, fizik muayene ve görüntüleme yöntemleri ile birlikte hemogram parametreleride göz önünde bulundurulmalıdır.

Anahtar sözcükler: Apandisit; gebelik; hemogram; lenfosit; nötrofil; teşhis.

Ulus Travma Acil Cerrahi Derg 2018;24(5):423-428

428

doi: 10.5505/tjtes.2018.62753

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

ORIG I N A L A R T IC L E

Role of preoperative C-reactive protein value and neutrophil ratio in the determination of conversion from laparoscopic appendectomy to open appendectomy Hüseyin Onur Aydın, M.D., Tevfik Avcı, M.D., Tugan Tezcaner, M.D., Mahir Kırnap, M.D., Sedat Yıldırım, M.D., Gökhan Moray, M.D. Department of General Surgery, Başkent University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: In this study, we aimed to investigate the factors causing conversion from laparoscopic appendectomy (LA) to open appendectomy (OA) in patients with acute appendicitis and to investigate the role of preoperative C reactive protein (CRP) and neutrophil ratio in this conversion and determine a cut-off point for these parameters.

METHODS: Records of patients who underwent LA due to acute appendicitis at our general surgery department between January 2011 and January 2017 were retrospectively evaluated. The preoperative American Society of Anesthesiology (ASA) scores, Alvarado scores, white blood cell count, C-reactive protein level, and neutrophil ratio were evaluated.

RESULTS: LA was performed in 394 patients with an initial diagnosis of acute appendicitis. A conversion to OA (cOA) was performed in 17 patients (4.31%). A CRP value of ≥108.5 mg/L and a neutrophil ratio of ≥81.5% were found to be statistically significant for the cOA (p<0.001).

CONCLUSION: Our study results showed that male gender, age, elevated neutrophil ratio, and CRP value were the main risk factors for cOA in patients who were scheduled for LA due to acute appendicitis.

Keywords: C-reactive protein; conversion to open surgery; laparoscopic appendectomy; neutrophil.

INTRODUCTION Acute appendicitis is one of the most common causes of acute abdominal pain. It is observed at a rate of 8.6% in males and 6.7% in females.[1] Before laparoscopic cholecystectomy, laparoscopic appendectomy (LA) was defined by Semm in 1983.[2] It may have a rapid duration of recovery, improved cosmetic results, and shorter duration of hospital stay compared to open appendectomy (OA); however, it has several disadvantages, such as a long duration of operation, high cost, and postoperative risk of intra-abdominal abscess development.[3] In the past two decades, with the increased knowledge and skills in laparoscopic techniques, LA has gained popularity for the treatment of acute appendicitis, and 75%

of all appendectomies are now being performed through laparoscopy.[4] However, there is still no consensus with regard to which technique is superior.

Several factors influence the conversion from LA to OA, including advanced age, male gender, obesity, intra abdominal abscess or perforation, and adhesions due to a previous abdominal surgery.[5] The conversion from the laparoscopic technique to the open technique leads to morbidities, such as prolongation of the operation time, increased cost, additional incision, prolonged duration of hospital stay, and postoperative wound infection. Therefore, many studies have been performed during the preoperative assessment to determine the most suitable technique for an individual patient. Although

Cite this article as: Aydın HO, Avcı T, Tezcaner T, Kırnap M, Yıldırım S, Moray G. Role of preoperative C-reactive protein value and neutrophil ratio in the determination of conversion from laparoscopic appendectomy to open appendectomy. Ulus Travma Acil Cerrahi Derg 2018;24:429-433.

Address for correspondence: Hüseyin Onur Aydın, M.D. Adres bilgisi: Başkent Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 215 26 29 E-mail: dronuraydin@hotmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):429-433 DOI: 10.5505/tjtes.2018.68705 Submitted: 14.06.2017 Accepted: 16.01.2018 Online: 10.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

429

Aydın et al. Conversion from laparoscopic appendectomy to open appendectomy

In the present study, we aimed to evaluate the factors affecting conversion from LA to OA in patients with acute appendicitis. For this purpose, we aimed to present the effect of preoperative characteristic features and laboratory findings on conversion from LA to OA.

MATERIALS AND METHODS The medical records of all consecutive patients aged above 18 years who had the diagnosis of acute appendicitis between January 2011 and January 2017 were retrospectively analyzed.

The patients who had no abdominal surgery history, no malignancy history, and no perforation findings in a radiological evaluation were included in the study. Among these patients, the file information of patients who underwent LA was evaluated. Patients were divided into two groups according to those completing appendectomy through laparoscopy or those converted from LA to OA. The study was approved by Baskent University Institutional Review Board (Project No: KA 17/91) and conducted in accordance with the principles of the Declaration of Helsinki.

Written informed consent was obtained from each patient.

LA was performed by a general surgeon who had at least a 5-year experience in laparoscopy or by a general surgery resident under the supervision of an experienced general surgeon. All operations were performed in a supine Trendelenburg and right side-up position. After positioning the patient, three trocars were placed in the umbilical region (camera port, 10–12 mm), suprapubic region (instrument port, 10–12 mm), and left lower quadrant (instrument port, 5 mm), and appendectomy was performed. The appendix stump was ligated with two 2/0 non-absorbable loops, which were prepared extracorporeally, and the appendix was removed using an endobag. In the patients who had a conversion to OA (cOA), a Mc Burney incision was performed on the right lower quadrant.

After ligating the appendix stump with a 2/0 non-absorbable suture, appendectomy was performed. In both groups, at the end of the operation, the abdominal cavity was irrigated with sterile isotonic solution, and in the presence of peritoneal inflammation and intra-abdominal abscess or perforation, intra abdominal drainage was performed.

Preoperative American Society of Anesthesiology (ASA) scores, Alvarado scores, white blood cell count (WBC), C-reactive protein (CRP) value, and neutrophil ratio were recorded. In addition, the presence of inflammation in the appendix, peritonitis, and intra-abdominal abscess, and the presence of appendix perforation and retrocecal appendix were evaluated. Postoperative pathology reports were examined.

A statistical analysis was performed using the SPSS version 430

19 software program (IBM Corp., Armonk, NY, USA). Demographic and clinical characteristics were expressed as frequency or percentage for categorical data, as mean standard deviation (±SD) for continuous parametric variables, and as median (interquartile ranges) for continuous non-parametric variables. The differences in preoperative and postoperative characteristics between the groups were evaluated using the Pearson’s chi-square test, two-sample t-test, Wilcoxon rank sum test, analysis of variance (ANOVA), or Kruskal–Wallis test, as appropriate. A univariate regression analysis was used to identify significant factors associated with cOA among patients who received LA and cOA. The receiver operating characteristic (ROC) analysis and area-under-curve (AUC) was performed to identify the cut-off values for WBC, CRP, and neutrophil ratio for cOA. A p value of <0.05 was considered statistically significant.

RESULTS A total of 669 patients were treated for acute appendicitis.

Among the 394 patients who underwent LA, 208 (52.79%) were females. The mean age of all patients was 35.8±13.87 years. Further, cOA was performed in 17 patients (4.31%).

The mean age of the patients who converted to OA was 42.47±21.1 years and that of patients who underwent LA was 35.59±13.4 years. The mean age of patients who converted to OA was significantly higher than the patients who underwent LA (p<0.05). Male gender was found to be more common in the cOA group (p<0.05). Demographic and clinical characteristics of patients are presented in Table 1.

The mean duration of the symptom onset was 1.63±1.30 days (range, 1–10 days). The most common diagnostic method was ultrasonography in 46.2% patients. The most common ROC Curve Preoperative neutrophil ratio 1.0 Preoperative CRC

0.8

Sensitivity

several factors that affect the conversion have been defined to date, there is still no certain algorithm.

0.6

0.4

0.2

0.0

0.0

0.2

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

1.0

Figure 1. ROC Curve analysis. AUC Neutrophil: 0.854; AUC CRP: 0.832.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aydın et al. Conversion from laparoscopic appendectomy to open appendectomy

Table 1. Demographic and clinical characteristics

Laparoscopic appendectomy

Number of patients Age (years)

Conversion to open appendectomy

377

17

35.59±13.4

42.47±21.1

Male/female

174/204

Alvorado score

p

<0.05

13/4 <0.05

6.23±1.71

6.88±1.65

ASA Score 1/2

290/71

3/4

16/0

11/4

2/0

Surgical findings, n (%)

Normal

Inflammation

9 (2.4)

0

325 (86.2)

3 (17.6)

Acute appendicitis

12 (3.2)

0 (0)

Intra-abdominal abscess

6 (1.6)

1 (5.9)

Perforated appendicitis

9 (2.4)

9 (52.9)

Retrocecal appendicitis

16 (4.2)

4 (23.5)

<0.05

Complication, n (%)

None

362 (96)

11 (64.7)

Wound enfection

9 (2.4)

1 (5.9)

Intraabdominal abscess

4 (1.1)

4 (23.5)

Postoperative ileus

1 (0.3)

1 (5.9)

Stump leakage

1 (0.3)

0 (0)

<0.05

Pathology, n (%)

Normal appendix

39 (10.3)

1 (5.9)

Acute appendicitis

314 (83.3)

13 (76.5)

Chronic inflammation

4 (1.1)

1 (5.9)

Mucoceles

6 (1.6)

0 (0)

Carcinoma

4 (1.1)

0 (0)

Perforated appendicitis

10 (2.7)

2 (11.8)

Duration of hospital stay (days)

1.41±0.96

4.24±2.16

Table 2. Preoperative laboratory findings

LA

cOA

>0.05

<0.05

Table 3. Factors influencing to conversion from LA to cOA p

p

Odds ratio

13.044±4039

14.229±390

0.237

CRP (mg/L)

≥108.5* <0.001

CRP (mg/L)

44.0±51.04

162.59±100.4

<0.001

Neutrophil (%)

≥81.5 <0.001 1.32 1.13–1.54

Neutrophil (%)

75.5±10.4

86.4±3.2

<0.001

WBC (mg/dL)

1.01

95% CI 1.0–1.02

*

*ROC curve cut-off points. ROC: receiver operating characteristic; LA: Laparo-

LA: Laparoscopic appendectomy; cOA: Conversion to open appendectomy; WBC: White blood cell; CRP: C-reactive protein.

scopic appendectomy; cOA: Conversion to open appendectomy; CI: Confidence

surgical finding was inflammation surrounding the appendix (83.2%), and the most common pathological result was acute appendicitis (83%). The mean duration of hospital stay was 1.41±0.96 days in the LA group and 4.24±2.16 days in the cOA group, indicating a significantly higher duration in the cOA group (p<0.01).

There was a higher rate of cOA (52.9%) observed in patients with appendix perforation detected during the surgery, indicating a statistical significance (p<0.05). The preoperative Alvarado scores, ASA scores, and the duration of onset of symptoms had no effect on cOA (p>0.05). WBC count was found to be higher in the cOA group compared to the LA

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

interval; CRP: C-reactive protein.

431

Aydın et al. Conversion from laparoscopic appendectomy to open appendectomy

group (LA, 13.044±4.039 mg/dL; cOA, 14.229±3.902 mg/ dL) although this difference was not statistically significant (p=0.816). In addition, CRP value and neutrophil ratio were found to be significantly higher in the cOA group (p<0.001; Table 2). ROC curve analysis and AUC for preoperative CRP and neutrophil ratio revealed that a CRP value of ≥108.5 mg/L and a neutrophil ratio of ≥81.5% were found to be statistically significant for cOA (Table 3 and Fig. 1).

DISCUSSION With the introduction of recent technical development and instruments, major advances have been achieved in laparoscopic surgery within the past decade. Considering the developments, LA is safely used for the treatment of acute appendicitis. However, the difference in superiority between LA and OA is uncertain. In the light of literature data, for patients undergoing LA, oral intake can be started sooner, and there is less analgesic requirement and shorter hospital stay.[6,7] However, cOA leads to increased costs, additional incision requirement, and prolonged hospital stay.[8] In the current study, we showed that the hospital stay in the cOA group was longer than that in the LA group. Although there was no difference in the postoperative complications between the two groups, the presence of an additional incision and the requirement of an additional antibiotic therapy in case of intra abdominal inflammation causing conversion led to the prolongation of hospital stay, which is consistent with previous study findings.[5] In the present study, cOA was demonstrated in 17 patients (4.31%) who underwent LA. This ratio is below 10%, which is consistent with the results reported in a previous meta analysis.[3] In addition, male gender was found to be 76.5% in the cOA group, and patients who converted to OA were found to be older compared to the LA group; these results were statistically significant (p<0.05). Similarly, previous studies showed that male gender and age ≥40 years were risk factors for cOA.[4,5] More frequent diagnostic laparoscopy in female patients with right lower abdominal pain could be a reason for the early diagnosis of acute appendicitis in female patients.[9] It has been reported that perforated appendicitis is seen more frequently in male patients, thereby increasing the rates of cOA in male patients.[10] Our results also showed that the conversion was more frequent in patients with appendix perforation.

Although the sensitivity of leukocytosis detection in peripheral blood is high in acute appendicitis, the specificity is known to be low because it is a known marker of inflammation.[11] In a study by Farooqui et al.,[12] it was demonstrated that the WBC count was higher, particularly in perforated appendicitis. In the current study, we found that the preoperative WBC count was higher in the cOA group. However, this elevation did not cause a statistically significant difference between the two groups. Although leukocytosis is an adjuvant test used in the diagnosis of acute appendicitis, laparoscopy 432

can be reliably performed in complicated appendicitis due to the advances in laparoscopic techniques. A meta-analysis by Yu et al.[13] showed that surgical-site infections, time to start oral feeding, and lengths of hospital stay were shorter in patients who underwent LA due to the complicated acute appendectomy compared to those who underwent OA. There may be an increase in the neutrophil ratio during bacterial infections. In several studies, the sensitivity of elevation of the neutrophil ratio was found to be between 85% and 98% in the diagnosis of acute appendicitis.[14,15] The neutrophil ratio was reported as an adjuvant parameter in the diagnosis of acute appendicitis; we found significantly higher rates in the cOA group compared to the LA group in our study (p<0.001). This can be attributed to the development of diffuse peritonitis, intra abdominal abscess, or plastrone appendicitis due to bacterial translocation. According to the ROC analysis, in addition, a neutrophil ratio of ≥81.5% was significant in the conversion to OA. It is well established that high CRP values are reliable in the diagnosis of acute appendicitis.[16] In literature, several studies have reported that CRP values were higher in patients who underwent cOA compared to those who underwent LA.[17,18] Similarly, in the current study, the CRP values in the cOA group were significantly higher than those in the LA group (p<0.001). According to the ROC analysis, a CRP value of ≥108.5 mg/L was a risk factor for the conversion to OA. This result may be explained by the high CRP value in patients with severe intra-abdominal inflammation that prevents laparoscopic dissection.

Our study has several limitations. The retrospective nature and the heterogeneity of patient groups are limiting factors.

Also, the decision of conversion to OA was determined by the attending surgeon and not by the apparent criteria. Despite these factors, we aimed to show statistically significant differences between the groups.

In conclusion, male gender, age, a neutrophil ratio of ≥81.5%, and a CRP value of ≥108.5 mg/L were risk factors for OA in patients who were scheduled for LA due to acute appendicitis. Therefore, patients with such risk factors can be switched from LA to OA. Conflict of interest: None declared.

REFERENCES 1. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990;132:910–25.

2. Semm K. Endoscopic appendectomy. Endoscopy 1983;15:59–64.

3. Sauerland S, Jaschinski T, Neugebauer EA. Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev 2010:CD001546.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aydın et al. Conversion from laparoscopic appendectomy to open appendectomy 4. Masoomi H, Nguyen NT, Dolich MO, Mills S, Carmichael JC, Stamos MJ. Laparoscopic appendectomy trends and outcomes in the United States: data from the Nationwide Inpatient Sample (NIS), 2004-2011.

Am Surg 2014;80:1074–7.

5. Finnerty BM, Wu X, Giambrone GP, Gaber-Baylis LK, Zabih R, Bhat A, et al. Conversion-to-open in laparoscopic appendectomy: A cohort analysis of risk factors and outcomes. Int J Surg 2017;40:169–75.

6. Nana AM, Ouandji CN, Simoens C, Smets D, Mendes da Costa P. Laparoscopic appendectomies: results of a monocentric prospective and non-randomized study. Hepatogastroenterology 2007;54:1146–52.

7. Yeh CC, Wu SC, Liao CC, Su LT, Hsieh CH, Li TC. Laparoscopic appendectomy for acute appendicitis is more favorable for patients with comorbidities, the elderly, and those with complicated appendicitis: a nationwide population-based study. Surg Endosc 2011;25:2932–42.

8. Chung RS, Rowland DY, Li P, Diaz J. A meta-analysis of randomized controlled trials of laparoscopic versus conventional appendectomy. Am J Surg 1999;177:250–6.

9. Laine S, Rantala A, Gullichsen R, Ovaska J. Laparoscopic appendectomy-is it worthwhile? A prospective, randomized study in young women.

Surg Endosc 1997;11:95–7.

10. Larsson PG, Henriksson G, Olsson M, Boris J, Ströberg P, Tronstad SE, et al. Laparoscopy reduces unnecessary appendicectomies and improves diagnosis in fertile women. A randomized study. Surg Endosc 2001;15:200–2.

11. Hallan S, Asberg A, Edna TH. Additional value of biochemical tests in suspected acute appendicitis. Eur J Surg 1997;163:533–8.

12. Farooqui W, Pommergaard HC, Burcharth J, Eriksen JR. The diagnostic value of a panel of serological markers in acute appendicitis. Scand J Surg 2015;104:72–8.

13. Yu MC, Feng YJ, Wang W, Fan W, Cheng HT, Xu J. Is laparoscopic appendectomy feasible for complicated appendicitis? A systematic review and meta-analysis. Int J Surg 2017;40:187–97.

14. Shafi SM, Afsheen M, Reshi FA. Total leucocyte count, C-reactive protein and neutrophil count: diagnostic aid in acute appendicitis. Saudi J Gastroenterol 2009;15:117–20.

15. Yang HR, Wang YC, Chung PK, Chen WK, Jeng LB, Chen RJ. Role of leukocyte count, neutrophil percentage, and C-reactive protein in the diagnosis of acute appendicitis in the elderly. Am Surg 2005;71:344–7.

16. Wu HP, Lin CY, Chang CF, Chang YJ, Huang CY. Predictive value of C-reactive protein at different cutoff levels in acute appendicitis. Am J Emerg Med 2005;23:449–53.

17. Abe T, Nagaie T, Miyazaki M, Ochi M, Fukuya T, Kajiyama K. Risk factors of converting to laparotomy in laparoscopic appendectomy for acute appendicitis. Clin Exp Gastroenterol 2013;6:109–14.

18. Antonacci N, Ricci C, Taffurelli G, Monari F, Del Governatore M, Caira A, et al. Laparoscopic appendectomy: Which factors are predictors of conversion? A high-volume prospective cohort study. Int J Surg 2015;21:103–7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ameliyat öncesi C-reaktif protein değeri ve nötrofil yüzdesinin laparoskopik apendektomiden açık apendektomiye konversiyonu belirlemedeki yeri Dr. Hüseyin Onur Aydın, Dr. Tevfik Avcı, Dr. Tugan Tezcaner, Dr. Mahir Kırnap, Dr. Sedat Yıldırım, Dr. Gökhan Moray Başkent Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ankara

AMAÇ: Çalışmamızda amacımız akut apandisit nedeniyle laparoskopik apendektomi (LA) uygulanan hastalarda açık apendektomiye (AA) konversiyona neden olan faktörleri incelenmektir. Ameliyat öncesi laboratuvar bulgularından C-reaktif protein (CRP) ve nötrofil yüzdelerinin konversiyona etkisini incelemek ve bu değerler için kesim değeri belirlemektir.

GEREÇ VE YÖNTEM: Merkezimizde, Ocak 2011–Ocak 2017 yılları arasında akut apandisit nedeniyle LA uygulanan hastaların dosya bilgileri geriye dönük olarak incelendi. Ameliyat öncesi American Society of Anesthesiology skoru, Alvorado skoru, beyaz küre sayısı, CRP düzeyi ve nötrofil yüzdesi değerlendirildi.

BULGULAR: Akut apandisit ön tanısıyla 394 hastaya LA uygulandı. On yedi (%4.31) hastada AA’ya konversiyon tespit edildi. C-reaktif protein değeri için 108.5 mg/L ve üstü değerler; nötrofil yüzdesi için %81.5 ve üstü değerlerde LA’dan AA’ya konversiyonun istatistiksel olarak anlamlı olduğu görüldü.

TARTIŞMA: Akut apandisit nedeniyle LA uygulanan hastalarda erkek cinsiyet, yaş, nötrofil yüzdesi ve CRP değerinin yüksek olması LA’dan AA’ya konversiyonda risk faktörü olduğu görülmüştür.

Anahtar sözcükler: Açık cerrahiye konversiyon; C-reaktif protein; laparoskopik apendektomi; nötrofil.

Ulus Travma Acil Cerrahi Derg 2018;24(5):429-433

doi: 10.5505/tjtes.2018.68705

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

433

ORIG I N A L A R T IC L E

A new and early marker in the diagnosis of acute complicated appendicitis: immature granulocytes Yılmaz Ünal, M.D. Department of General Surgery, Ankara Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: The aim of this study was to investigate the effectiveness of the immature granulocyte (IG) count (IGC) and percentage (IG%) in both diagnosing acute appendicitis (AA) and discriminating between simple appendicitis (SA) and complicated appendicitis (CA).

METHODS: This study was carried out using the data of 438 adult patients who underwent an appendectomy. Demographic details, the preoperative white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), IGC and IG%, operation findings, and pathology results were assessed retrospectively. The patients were grouped as AA and normal appendix (NA) according to the pathology reports, and the AA cases were subdivided into SA and CA groups according to the intraoperative findings.

RESULTS: WBC, NLR, IGC, and IG% were significant parameters in the diagnosis of AA. The area under the receiver operating characteristic curve (AUROC: 0.795), sensitivity (55.5%) and specificity (96.1%) values of IGC were higher than the other parameters.

All of the parameters were also significant for a CA diagnosis; however, the value of IG% in a CA diagnosis was stronger than the other parameters (IG% AUROC: 0.979, sensitivity: 94.4%, specificity: 97.9%).

CONCLUSION: The IG value is a fast, easily available, and reliable parameter in both diagnosing AA and discriminating between SA and CA. Keywords: Appendicitis; diagnosis; immature granulocytes.

INTRODUCTION Acute appendicitis (AA) is the most frequent cause of acute abdominal pain and typically requires emergency surgical intervention; an appendectomy is the most frequently performed emergency operation.[1] Almost 8% of the general population in Western countries will undergo an appendectomy during their lifetime.[2] Most AA cases are simple appendicitis (SA) without complications. The perforation rate is typically between 20% and 30%; however, this rate can be as high as 50% in elderly patients.[3,4] Acute complicated appendicitis (CA) is a serious problem that increases the risk of postoperative complications, delays recovery, and increases the length of hospital stay and medical costs.[5] Therefore, early diagnosis and treatment of CA is critically important.[6]

Numerous studies have been carried out to improve the early diagnosis and treatment of acute complicated appendicitis (ACA). Researchers have used various biomarkers for this purpose, including the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and bilirubin levels, and the neutrophil/lymphocyte ratio (NLR).[7–13] However, despite the use of all of these biomarkers as well as radiological methods, it is still difficult to clearly differentiate between SA and CA. There is need for a more specific biomarker for this discrimination.

Immature granulocytes (IG) in the peripheral blood is an indicator of increased bone marrow activation.[14] Due to technical developments in automated hematological analyzers, the quantity of IG can easily be measured when performing a

Cite this article as: Ünal Y. A new and early marker in the diagnosis of acute complicated appendicitis: immature granulocytes. Ulus Travma Acil Cerrahi Derg 2018;24:434-439.

Address for correspondence: Yılmaz Ünal, M.D. Ankara Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara, Turkey Tel: +90 312 - 595 30 00 E-mail: yilmazunal66@mynet.com Ulus Travma Acil Cerrahi Derg 2018;24(5):434-439 DOI: 10.5505/tjtes.2018.91661 Submitted: 26.04.2018 Accepted: 04.09.2018 Online: 20.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

434

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Ünal. Immature granulocytes

routine complete blood count (CBC) and be presented as a new inflammation biomarker.[14–16] Studies have shown that IG count (IGC) and percentage (IG%) are significantly increased in sepsis and infections when compared with healthy individuals.[16–18] This study was an investigation of the effectiveness of IG, a new marker of inflammation, in both diagnosing AA and discriminating between SA and CA.

variables that did not have a normal distribution. Receiving operating characteristic (ROC) curve analysis was performed in order to determine the success of laboratory parameters in predicting cases of AA and CA. The threshold values were identified using the Youden index. The specificity values were calculated based on the obtained threshold values. The value of p<0.05 was accepted as statistically significant.

MATERIALS AND METHODS

RESULTS

This study was carried out retrospectively from April 2017 to February 2018 on 438 adult patients (>18 years) who underwent an appendectomy with a prediagnosis of AA at the General Surgery Clinic of the Ankara Training and Research Hospital. Patients under the age of 18 years, pregnant women, and those with additional diseases that could affect inflammation markers were excluded from the study. Moreover, people who were hospitalized with a prediagnosis of AA and discharged from hospital after receiving medical treatment were not included in the study. The demographic data, laboratory values, operation findings, and pathology results of the 438 patients included in the study were analyzed using the records of the hospital database.

The present study included 438 patients who underwent an appendectomy with a prediagnosis of AA. Of the group, 234 of the patients (53.4%) were male, while 204 were female (46.6%). The median age was 30 years (17,25). The youngest patient was aged 18 years, and the oldest 92.

For patients who presented at the emergency department with acute abdominal pain, after obtaining the clinical history and providing physical treatment, a CBC was performed if there was a suspicion of AA. WBC count, neutrophil count, lymphocyte count, and IG% were measured using an automated hematological analyzer (XN 3000; Sysmex Corp., Kobe, Japan) from blood samples obtained preoperatively at the initial admission to the emergency department. The NLR and IGC were calculated using the data obtained from the CBC analysis.

The cases were divided into 2 groups: AA and normal appendix (NA; negative appendectomy) according to the pathology reports. The AA group was subdivided into cases of simple acute appendicitis (ASA) (catarrhal and phlegmonous) and complicated acute appendicitis (ACA) (gangrenous, perforated, and abscess). The demographic data and preoperative laboratory findings were analyzed statistically and compared.

Statistical Analysis The data were assessed using the IBM SPSS Statistics for Windows, Version 22.0 software package (IBM Corp., Armonk, NY, USA). The number of units (n) and percentage (%), mean (±), SD (x±ss), and median (interquartile range [IQR]) values were provided as descriptive statistics. The Pearson chisquare and Fischer’s exact tests were used to assess categorical variables. Numerical variables with a normal distribution were assessed with the Shapiro-Wilk test, normality test, and Q-Q graphics. When comparing 2 groups, the independent sample t-test was used for variables demonstrating normal distribution, while the Mann-Whitney U analysis was used for Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

According to the pathology results, 412 of the patients (94.07%) were found to have AA and 26 (5.93%) had NA. The rate of NA was higher among women than men (8.3% and 3.8%, respectively), which was a statistically significant difference (p=0.047). In the AA group, the mean values of WBC, NLR, IGC, and IG% were significantly higher than in the NA group (p<0.001 for all of the parameters). The comparison between the NA and AA groups is presented in Table 1.

The 412 patients diagnosed with AA pathologically were grouped as ASA and ACA. Of these 412 patients, 340 (82.9%) were in the ASA group, while 72 (17.9%) were ACA cases.

No significant difference was found between the ASA and ACA groups in terms of gender (p=0.223). The mean age of the patients was determined to be higher in the ACA group than in the ASA group (p<0.001).

The mean WBC, NLR, IGC, and IG% in the ACA group was found to be significantly higher than in the SAA group (p<0.001 for all of the parameters). The comparison between the ASA and ACA groups is provided in Table 2.

Table 1. The comparison of demographic data and

laboratory findings between acute appendicitis

and normal appendix

Acute Normal p appendicitis appendix

Number of patients

412 (94.7%)

26 (5.9%)

Female

187 (91.7%)

17 (8.3%)

Male

225 (94.07%)

9 (3.8%)

WBC (µL)

14700 (5900) 10550 (68500)

NLR IGC (µL) IG%

0.047 0.047 <0.001

5.4 (5)

3.08 (2.9)

<0.001

65.6 (49.2)

38.3 (31.7)

<0.001

0.4 (0.2)

0.3 (0.1)

<0.001

IG%: Immature granulocyte percentage; IGC: Immature granulocyte count; NLR: Neutrophil-to-lymphocyte ratio; WBC: White blood cell.

435

Ünal. Immature granulocytes

Table 2. The comparison of demographic data and

laboratory findings between simple and

complicated appendicitis groups

Simple Complicated appendicitis appendicitis

Number of patients

340 (82.5%)

72 (17.5%)

159 (85%)

28 (15%)

=0.223

181 (80.4%)

44 (19.6%)

=0.223

29.5 (16)

36.5 (25.75)

<0.001

Male Age (years) WBC (µL)

14050 (54500) 18350 (55300)

NLR IGC (µL) IG%

DISCUSSION

<0.001

4.9 (4.4)

8.8 (6.9)

<0.001

56.4 (38.7)

146.4 (59.1)

<0.001

0.4 (0.2)

0.8 (0.1)

<0.001

IG%: Immature granulocyte percentage; IGC: Immature granulocyte count; NLR: Neutrophil-to-lymphocyte ratio; WBC: White blood cell.

ROC curves were drawn in order to calculate the effectiveness of laboratory parameters (WBC, NLR, IGC, IG%) to diagnose AA and to discriminate between ASA and ACA (Fig. 1 and 2). The prediction ability of all of the parameters to diagnose AA and differentiate between ASA and ACA was significant (p<0.001 for all of the parameters). However, the ability of IGC to predict AA was greater than that of the other parameters (IGC area under the ROC [AUROC]: 0.795, sensitivity: 55.9%, specificity: 96.1%). The results of the ROC analysis can be seen in Table 3.

While the prediction ability of the IG% in AA diagnosis was similar to that of the other parameters, its ability to discriminate between ASA and ACA was considerably greater than the others (AUROC: 0.979, sensitivity: 94.4%, specificity: 97.9%) (Table 4). When the IG% and the IGC were compared ROC Curve

1.0

Sensitivity

0.8

0.6

Source of the Curve IG% IG_SAYI NLR WBC Reference Line

0.4

0.2

0.0

The NA rate in this study was 5.97%, which was lower than the rates reported in the literature. This low rate resulted from the application of a non-operative treatment approach.

[23] This refers to patients who were hospitalized on suspicion of AA and showed improvements in clinical and laboratory findings through medical treatment. This patient group was discharged without being operated on and was not included in the study. The NA rate was significantly higher among women than men, which was consistent with the literature.

It is thought that this discrepancy might have arisen from difficulties in discriminating AA from emergency gynecological pathologies among young women.

The CA rate was 17.5% in the present study and it was observed at older ages compared with the incidence of SA. ThROC Curve

1.0

0.8

0.6

Source of the Curve IG% IG_SAYI NLR WBC Reference Line

0.4

0.2

0.0

0.2

0.4 0.6 0.8 1.0 1 - Specificity Diagonal segments are produced by ties

Figure 1. Receiver operating characteristic curve analysis of laboratory parameters in the discrimination between normal appendix and acute appendicitis.

436

AA is the most common reason for emergency abdominal surgery all around the world.[1] Laboratory tests, scoring systems and imaging methods are used in AA diagnosis, as well as the clinical history and physical examination.[19] However, it is not always possible to make a final and accurate diagnosis.

Despite all of the developments in diagnosis and treatment methods, high NA and perforation rates have still been reported (13–36%, 12–21%, respectively).[4,10,12,19–22] Perforation rates can reach 50%, particularly among the elderly.[3,5,6,22] As perforation rates increase, the rates of morbidity and mortality, the duration of hospital stay, and medical costs increase as well. Therefore, new biomarkers are needed in order to reduce the rate of both NA and CA.

Sensitivity

Female

p

with respect to their ability to discriminate between ACA and ASA, it was observed that the IG% had a greater ability to discriminate CA from SA but the IGC had a greater ability to discriminate AA from NA.

0.0

0.0

0.2

0.4 0.6 0.8 1.0 1 - Specificity Diagonal segments are produced by ties

Figure 2. Receiver operating characteristic curve analysis of laboratory parameters in the discrimination between simple appendicitis and complicated appendicitis.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Ünal. Immature granulocytes

Table 3. The ROC analysis of parameters in the prediction of acute appendicitis

AUROC

White blood cell

0.763

95% confidence interval

Cut-off

Sensitivity (%)

Specificity (%)

p

Lower limit Upper limit 0.679

0.847

>14800/(µL)

48.7

92.3

0.001

Neutrophil-to-lymphocyte ratio

0.713

0.599

0.828

>3.5

73.3

69.2

0.001

Immature granulocyte count

0.795

0.724

0.867

>60.5/(µL)

55.5

96.1

0.001

Immature granulocyte percentage

0.739

0.658

0.821

>0.4

47

88.4

0.001

Cut-off

Sensitivity (%)

Specificity (%)

p

AUROC: Area under the ROC curve; ROC: Receiver operating characteristic.

Table 4. ROC analysis of parameters in predicting complicated appendicitis

AUROC

White blood cell

0.798

95% confidence interval

Lower limit Upper limit 0.737

0.859

>15800/(µL)

75

70.2

0.001

Neutrophil-to-lymphocyte ratio

0.760

0.705

0.816

>5.6

79.1

61.1

0.001

Immature granulocyte count

0.968

0.948

0.988

>104.4/(µL)

93

93.8

0.001

Immature granulocyte percentage

0.979

0.955

1.000

>0.6

94.4

97.9

0.001

AUROC: Area under the ROC curve; ROC: Receiver operating characteristic.

ese results were also consistent with the literature.[5,6,22] This might be because elderly people often present to hospital late because their AA symptoms are obscure.

In AA diagnosis, a high WBC count is significant, but not diagnostic. The physiological response of leukocytes in circulation to stress leads to an increase in neutrophil numbers and a decrease in lymphocyte numbers. Thus, the ratio of these 2 subgroups (NLR) is used as a parameter of inflammation.[7–13] In a study designed by Kahramanca et al.[9] it was determined that NLR was a useful parameter for diagnosing AA and discriminating between SA and CA. In a study involving 3392 cases, Sevinç et al.[12] found that the WBC count was not a significant parameter in CA diagnosis, though it was significant in diagnosing AA. Moreover, they stated that a serum bilirubin level greater than 1.0 mg/dL and an NLR greater than 4.8 contributed to perforation in patients with acute abdominal pain. Bröker et al.[10] and Moon et al.[24] found that the possibility of CA increased in cases in which the CRP level was high, suggesting that proper treatment be carried out immediately in these cases. In the present study, an NLR >3.5 supported an AA diagnosis and an NLR >5.6 supported a diagnosis of CA. An increase of IG in circulation is a reaction of the blood marrow against bacterial infection. In recent years, it has been possible to detect the percentage and number of IG due to technical developments in automated hematological analyzers.

[14–16] Recent studies have demonstrated that IG can be used Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

as an effective inflammatory marker.[15,17,18,25–27] Studies on the use of IG measurements in AA diagnosis and the discrimination between SA and CA are limited.[22,28,29] Mathews et al.[28] found that an increased IG% was significant in the discrimination of acute and perforated appendicitis in the pediatric age group, but it did not bring any additional benefit to this discrimination when compared with an increased CRP level and shift to left. Shin et al.[22] found that the delta neutrophil index (DNI), the IG fraction in circulation, was a reliable marker in discriminating between acute non-perforated appendicitis and acute perforated appendicitis among elderly individuals.

Furthermore, they recommended carrying out immediate CT and emergency surgical intervention in elderly patients with suspicious appendicitis and a DNI >1.4. In another study, Shin et al.[29] measured the DNI for use in discrimination between AA and CA among adults and showed that a DNI >2 could be a reliable parameter for AA and DNI >6 could identify CA. In the present study, there was a statistically significant difference between the NA and AA groups in all of the hematological parameters (WBC, NLR, IGC, IG%). However, it was determined that the IGC was quite specific in diagnosing AA (AUROC: 0.795, sensitivity: 55.5%, specificity: 96.1%). Moreover, all of the parameters were statistically significant when the SA and CA groups were compared; however, the IG% had a greater ability to predict CA than the other parameters (AUROC: 0.979, sensitivity: 94.4%, specificity: 97.9%).

This study had certain limitations. Since it was a retrospective study, the data obtained were limited. Therefore, the inflam437

Ünal. Immature granulocytes

mation parameters, such as CRP, were not included in the study. As measurement of the IG parameter in the CBC did not exist prior to April 2017, this study included cases after this date. Thus, the number of patients was limited. Furthermore, the length of time from the emergence of symptoms until presentation at the hospital could not be assessed. It is possible that this period affects the values of inflammatory markers.

Conclusion Early diagnosis and treatment of ACA is very important since it reduces postoperative morbidity rates and medical costs. IG is a new inflammatory marker that is easily detected through a routine CBC without any additional time or cost.

Based on the results of this study, it can be said that in cases of suspicious acute appendicitis, the IGC is a more reliable marker in predicting AA than the other hematological parameters, while the IG% is a more reliable marker in predicting ACA. Conflict of interest: None declared.

REFERENCES 1. Debnath J, Kumar R, Mathur A, Sharma P, Kumar N, Shridar N, et al.

On the role of ultrasonography and CT scan in the diagnosis of acute appendicitis. Indian J Surg 2015;77:221–6.

2. Nshuti R, Kruger D, Luvhengo TE. Clinical presentation of acute appendicitis in adults at the Chris Hani Baragwanath Academic Hospital. Int J Emerg Med 2014;7:12 3. Franz MG, Norman J, Fabri PJ. Increased morbidity of appendicitis with advancing age. Am Surg 1995;61:40–4.

4. Yamini D, Vargas H, Bangard F, Klein S, Stamas MJ. Perforated appendicitis: is it truly a surgical urgency? Am Surg 1998;64:970–5.

5. Lee JF, Leow CK, Lau WY. Appendicitis in the elderly. ANZ J Surg 2000;70:593–6.

6. Lunca S, Bouras G, Romedea NS. Acute appendicitis in the elderly patient: diagnostic problems, prognostic factors and outcomes. Rom J Gastroenterol 2004;13:299–303.

7. Paragiotopoulou IG, Parashar D, Lin R, Antonowicz S, Wells AD, Bojura FM, et al. The diagnostic value of white cell count, C-reactive protein and bilirubin in acute appendicitis and its complications. Ann R Coll Surg Engl 2013;95:215–21.

8. Farooqui W, Pommergaard HC, Burcharth J, Eriksen JR. The diagnostic value of a panel of serological markers in acute appendicitis. Scand J Surg 2015;104:72–8.

9. Kahramanca S, Ozgehan G, Seker D, Gökce EI, Seker G, Tunç G, et al.

Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2014;20:19–22.

10. Bröker ME, van Lieshout EM, van der Elst M, Stassen LP, Schepers T. Discriminating between simple and perforated appendicitis. J Surg Res 2012;176:79–83.

11. McGoran DR, Sims HM, Zia K, Uheba M, Shaikh IA. The value of biochemical markers in predicting a perforation in acute appendicitis. ANZ J Surg 2013;83:79–83.

438

12. Sevinç MM, Kınacı E, Çakar E, Bayrak S, Özakay A, Aren A, et al. Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. Ulus Travma Acil Cerrahi Derg 2016;22:155–62.

13. Jung SK, Rhee DY, Lee WJ, Woo SH, Seol SH, Kim DH, et al. Neutrophil-to-lymphocyte count ratio is associated with perforated appendicitis in elderly patients of emergency department. Aging Clin Exp Res 2017;29:529–36.

14. Senthilnayagam B, Kumar T, Sukumaran J, M J, Rao KR. Automated measurement of immature granulocytes: performance characteristics and utility in routine clinical practice. Pathol Res Int 2012;2012:483670.

15. Park JH, Byeon HJ, Lee KH, Lee JW, Kronbichler A, Eisenhut M, et al. Delta neutrophil index (DNI) as a novel diagnostic and prognostic marker of infection: a systematic review and meta-analysis. Inflamm Res 2017;66:863–70.

16. Ansari-Lari MA, Kickler TS, Borowitz MJ. Immature granulocyte measurement using the Sysmex XE-2100. Relationship to infection and sepsis. Am J Clin Pathol 2003;120:795–9.

17. Nigro KG, O’Riordan M, Molloy EJ, Walsh MC, Sandhaus LM. Performance of an automated immature granulocyte count as a predictor of neonatal sepsis. Am J Clin Pathol 2005;123:618–24.

18. Park BH, Kang YA, Park MS, Jung WJ, Lee SH, Lee SK, et al. Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis. BMC Infect Dis 2011;11:299.

19. Ozan E, Ataç GK, Alişar K, Alhan A. Role of inflammatory markers in decreasing negative appendectomy rate: A study based on computed tomography findings. Ulus Travma Acil Cerrahi Derg 2017;23:477–82.

20. Joshi MK, Joshi R, Alam SE, Agarwal S, Kumar S. Negative Appendectomy: an Audit of Resident-Performed Surgery. How Can Its Incidence Be Minimized? Indian J Surg 2015;77:913–7.

21. Kartal K, Yazıcı P, Ünlü TM, Uludağ M, Mihmanlı M. How to avoid negative appendectomies: Can US achieve this? Ulus Travma Acil Cerrahi Derg 2017;23:134–8.

22. Shin DH, Cho YS, Kim YS, Ahn HC, Oh YT, Park SO, ET AL. Delta neutrophil index: A reliable marker to differentiate perforated appendicitis from non-perforated appendicitis in the elderly. J Clin Lab Anal 2018;32.

23. Turhan AN, Kapan S, Kütükçü E, Yiğitbaş H, Hatipoğlu S, Aygün E. Comparison of operative and non operative management of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2009;15:459–62.

24. Moon HM, Park BS, Moon DJ. Diagnostic value of C-reactive protein in complicated appendicitis. J Korean Soc Coloproctol 2011;27:122–6.

25. Lee H, Kim IK, Ju MK. Which patients with intestinal obstruction need surgery? The delta neutrophil index as an early predictive marker. Ann Surg Treat Res 2017;93:272–6.

26. Lipiński M, Rydzewska G. Immature granulocytes predict severe acute pancreatitis independently of systemic inflammatory response syndrome.

Prz Gastroenterol 2017;12:140–4.

27. Lee JW, Kim SH, Park SJ, Lee KH, Park JH, Kronbichler A, et al. The value of delta neutrophil index in young infants with febrile urinary tract infection. Sci Rep 2017;7:41265.

28. Mathews EK, Griffin RL, Mortellaro V, Beierle EA, Harmon CM, Chen MK, et al. Utility of immature granulocyte percentage in pediatric appendicitis. J Surg Res 2014;190:230–4.

29. Shin DH, Cho YS, Cho GC, Ahn HC, Park SM, Lim SW, et al. Delta neutrophil index as an early predictor of acute appendicitis and acute complicated appendicitis in adults. World J Emerg Surg 2017;12:32.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Ünal. Immature granulocytes

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut komplike apandisit tanısında yeni ve erken bir belirteç: İmmatür granülosit Dr. Yılmaz Ünal Ankara Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Çalışmamızın amacı immatür granülosit sayısı (IGS) ve yüzdesinin (IG%) hem akut apandisit tanısında hem de basit apandisit (BA) ile komplike apandisiti (KA) ayırmadaki etkinliğini araştırmaktır.

GEREÇ VE YÖNTEM: Bu çalışma apendektomi yapılan 438 erişkin hasta üzerinde yapıldı. Hastaların demografik verileri, beyaz küre (BK) sayımı, nötrofil/lenfosit oranı (NLO), IGS ve IG%’si, ameliyat bulguları ve patoloji sonuçları geriye dönük olarak değerlendirildi. Hastalar patoloji raporlarına göre akut apandisit (AA) ve normal apendiks (NA) olarak, akut apandisitler de ameliyattaki bulgulara göre BA ve KA olarak gruplara ayrıldı.

BULGULAR: Beyaz küre, NLO, IGS, IG% akut apandisit tanısında anlamlı parametrelerdi. Bu parametrelerin arasında IGS’nin AUROC, duyarlılık ve özgüllük değerleri diğerlerinden daha yüksek idi. IGC için AUROC; 0.795, duyarlılık: %55.5, özgüllük: %96.1 idi. Tüm parametreler komplike apandisit tanısında da anlamlı idi ancak IG%’nin komplike apandisit tanısındaki değeri diğer parametrelerden daha güçlü idi (AUROC: 0.979, duyarlılık: %94.4, özgüllük: %97.9 idi.

TARTIŞMA: İmmatür granülosit hem akut apandisit tanısı koymada, hem de basit ve komplike apandisiti ayırmada hızlı, kolay ulaşılabilir ve güvenilir bir parametredir.

Anahtar sözcükler: Apandisit; immatüre granülosit; tanı.

Ulus Travma Acil Cerrahi Derg 2018;24(5):434-439

doi: 10.5505/tjtes.2018.91661

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

439

ORIG I N A L A R T IC L E

Legal and ethical responsibilities of physicians in coercive situations, such as natural disasters Berna Şenel Eraslan, M.D.,1 Beytullah Karadayı, M.D.,1 İbrahim Eray Çakı, M.D.,1 Naciye Aslan, M.D.,2 Ende Varlık Tokgözoğlu, M.D.,1 Çağlayan Kılıç, M.D.,3 Abdi Özaslan, M.D.,1 Gürsel Çetin, M.D.1 1

Department of Forensic Medicine, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

2

Ministry of Justice, Concile of Forensic Medicine, İstanbul-Turkey

3

İstanbul Medeniyet University, Graduate School of Social Sciences, İstanbul-Turkey

ABSTRACT BACKGROUND: The relationship between the physician and the patient is based on the provisions of the proxy agreement. The attitude of the physician and the legal and ethical responsibilities of this attitude in an event of force majeure, such as severe natural disaster (earthquake), during a risky operation should be discussed. The aim of the present study was to present the opinions of the related professions about the subject and to discuss the subject on an ethical and legal ground.

METHODS: A total of 207 volunteers including 121 physicians working at the Cerrahpasa Faculty of Medicine at Istanbul University and 86 lawyers registered at the Istanbul Bar Association completed the questionnaires. Statistical analysis of data acquired from the questionnaires was performed using SPSS 21.0.

RESULTS: Of the participants, 76.8% stated that abandoning the patient by the physician considering his/her own safety during a severe natural disaster is ethically problematic. However, 68.1% of the participants stated that physicians would not be facing any criminal sanctions in response to his/her attitude. When the answers from both occupational groups were compared separately, it was found that 26.4% of the physicians and 39.5% of the lawyers stated that the act in question has both legal and ethical liability.

CONCLUSION: In the present study, no complete consensus was observed either between or within two occupational groups. It was concluded that the meetings in which the subject is discussed and is based on a concrete ground by both occupational groups should be held.

Keywords: Coercive situations; ethical responsibility of the physician; legal responsibility of the physician; natural disasters.

INTRODUCTION The proxy agreement or the work contract is considered as the legal basis of the relationship between the patient and the physician. While the relationship between the patient and the physician is subjected to the work contract in aesthetic operations that would require the guarantee of the results, all the other types of relationship between the patient and the physician are subjected to the proxy agreement.[1–3] The proxy stated in the proxy agreement is responsible for the

careful efforts that he/she has undertaken in order to achieve the results, not for achieving the results. Accordingly, the physician commits to do his/her best to treat the patient and eliminates the patient’s complaints but does not guarantee the result.[2,4,5] It is known that employees in the healthcare system are very restricted in not accepting or leaving the patient. The case of not accepting the patient can come into question in the presence of trust issues. Even in these cases, according to

Cite this article as: Şenel Eraslan B, Karadayı B, Çakı İE, Aslan N, Varlık Tokgözoğlu E, Kılıç Ç, et al. Legal and ethical responsibilities of physicians in coercive situations, such as natural disasters. Ulus Travma Acil Cerrahi Derg 2018;24:440-444.

Address for correspondence: Berna Şenel Eraslan, M.D. İstanbul Ünicersitesi Cerrahpaşa Tıp Fakültesi, Adli Tıp Anabilim Dalı, 34098 Fatih, İstanbul, Turkey Tel: +90 212 - 414 30 29 E-mail: drbsenel@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):440-444 DOI: 10.5505/tjtes.2017.32885 Submitted: 24.07.2017 Accepted: 26.09.2017 Online: 12.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

440

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Şenel Eraslan et al. Legal and ethical responsibilities of physicians in coercive situations, such as natural disasters

the medical deontology regulations, the physician should not abandon the patient due to personal or professional reasons in cases of emergency, official or human duties before the treatment is completed.[6] In cases, such as assault, violence, and verbal annoyance, that constitute trust issues within the frame of proxy agreement, the physician will, of course, face the problems, providing patient’s healthcare. In such cases that are exceptional from the cases indicated in the medical deontology regulations, if the physician wishes to discontinue the treatment and follow-up his/her patient, he/she may transfer the patient to another colleague by calculating the time that will not disrupt the treatment beforehand and by notifying the patient in due time.[6] If working in an institution, the administrators should be informed and are asked for assistance.

Even though the patients can choose the hospital and the physician to be treated within certain frames, the physician has no right to choose the patient.[3,7] The real reason behind this is that the right to life is prioritized within the concept of the civil law. The ethical and legal responsibilities of an employee that works in the healthcare system in case of an unexpected situation that threatens his/her life should be discussed. To our knowledge, thus far, there is no regulation, doctrine, or literature present about the attitude of a physician in case of unexpected situations, such as severe natural disasters, that can harm both the patient and the physician.

The aim of the present study was to present the opinions of the physicians and the attorneys and to discuss it on ethical and legal grounds.

MATERIALS AND METHODS

The volunteers were asked whether the attitude of the physician was ethically faulty in the fifth question, and whether the physician had legal and criminal liability due to his/her attitude in the sixth question.

Statistical analyses of the answers given to the questionnaires were conducted using descriptive statistics and graphical analysis tests using SPSS 21.0 (IBM). Statistical differences between the answers of the groups were analyzed using Fisher’s exact test and chi-square fitness test.

RESULTS The mean age of the 121 physicians was 37.43±11.94 years, and 56.2% (n=68) and 43.8% (n=53) of them were males and females, respectively, whereas the mean age of the 86 attorneys was 28.48±7.26 years, and 40.7% (n=35) and 59.3% (n=51) of them were males and females, respectively.

The professional experiences of the physicians and the attorneys were 12.58±11.96 and 4.21±6.84 years, respectively.

The academic ranks of the physicians were 50.4% (n=61) as physician assistant, 18.2% (n=22) as specialist, and 31.4% (n=38) as lecturer.

Of the participants, 76.8% stated that physician’s abandonment of the patient considering his/her own safety during a severe natural disaster possesses ethical problems (Fig. 1).

Evaluation of the answers from two occupational groups revealed that 77.7% (n=94) of the physicians and 75.6% (n=65) of the attorneys found the attitude ethically wrong (Fig. 2).

The answers from each occupational group were not statically significantly different (p>0.05).

The study was conducted on physicians working at the Cerrahpasa Faculty of Medicine at Istanbul University and attorneys registered at the Istanbul Bar Association between January 1 and March 31, 2015. Between the indicated dates, face-to-face interviews were conducted with the physicians and the attorneys, and the participants were informed about the six-question survey entitled “Ethical and legal responsibility of the physicians in case of an event of force majeure, such as earthquake.”

Of the participants, 68.1% (n=141) stated that the physician would not be faced with criminal liability due to his/her attitude (Fig. 3). However, when the answers from two occupational groups were evaluated separately, 26.4% (n=32) of the physicians and 39.5% (n=34) of the attorneys stated that the act in question has both legal and ethical liability (Fig. 4). Chisquare analysis revealed a significant difference between the answers from two groups (p<0.05).

A total of 207 volunteers including 121 physicians and 86 attorneys expressed their verbal consents and answered the questionnaires. Face-to-face surveys were conducted to prevent repetitive participation.

Of the physicians, 72% (n=85) were working outside of the surgical branches. The comparison of answers from the questionnaires of the physicians working in surgical branches and nonsurgical branches revealed no significant differences (p>0.05).

The first four questions were about age, gender, profession, and duration of work in the profession and were used to determine personal information. In the next stage, the volunteers were asked to read the scenario: “A large earthquake hit during a risky operation in a hospital. Earthquake caused cracks on the walls and toppling of some items. The surgery team abandoned the building. When the team returned to the operating room they realize that the patient had died.”

Of the physicians with experience >10 years, 91.1% (n=51) found the attitude ethically wrong, whereas of those with experience <10 years, 67.2% (n=43) found it ethically wrong.

Statistical analyses between the two groups were highly significant (p<0.01). Statistical analysis depending on the professional experience of the attorneys (experienced >10 years or <10 years) was not conducted as the distribution of data was insufficient.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

441

Şenel Eraslan et al. Legal and ethical responsibilities of physicians in coercive situations, such as natural disasters

Ethically Responsibility

Legal Liability

There should be legal and criminal liability (31.88%)

Not ethically wrong (23.19%)

There should be no legal and criminal liability (68.12%)

Ethically wrong (76.81%)

Figure 1. All participants’ opinions about the ethical responsibilities of the physicians in coercive situations, such as natural disasters.

Figure 3. All participants’ opinions about the legal and criminal responsibilities of the physicians in coercive situations, such as natural disasters.

Ethically responsibility

80.000

80.000

Physician Attorney

70.000

70.000 60.000

60.000

50.000 77.69%

%

%

50.000 40.000

75.58%

40.000 20.000

20.000 22.31%

10.000

24.42%

10.000 0.000

Ethically wrong

73.55%

30.000

30.000

0.000

Legal Liability

Physician Attorney

Not ethically wrong

26.45%

60.47%

39.53%

There should be legal and criminal liability

There should be no legal or criminal liability

Figure 2. Doctors’ and lawyers’ opinions about the ethical responsibilities of the physicians in coercive situations, such as natural disasters.

Figure 4. Doctors’ and lawyers’ opinions about the legal and criminal responsibilities of the physicians in coercive situations, such as natural disasters.

DISCUSSION

ipants believe that there should be a legal sanction. Thus, it is possible to state that the case creates an ethical concern rather than legal sanction by the two occupational groups.

On the other hand, 77.7% (n=94) of the physicians and 76.5% (n=65) of the attorneys stated that the act in question is ethically wrong. This opinion might be due to the life-threatening risk that is much higher for the patient than for the physician under surgery conditions. In addition, it might be since being a physician is raised to an unrealistic level where human life is entrusted to the physician.

All the measures taken are evaluated as the patient safety by the healthcare providers and their employees to prevent the harms that can be caused by those factors.[8] In this context, operating rooms are complicated places where the patient’s life is at risk due to intense pressure, competing with time and lack of qualified person.[9] On the other hand, operating rooms are covered under the places where the patient’s safety is the priority under natural disaster circumstances, such as an earthquake. This subject was found worthwhile to study due to the lack of doctrine, regulation, or literature about the action of the physician on duty during extraordinary situations, such as earthquakes, and conducted in order to evaluate the differences in the perspectives of the physicians and the attorneys.

In the study, the questionnaire for opinions about the legal and ethical responsibilities during coercive situations, such as an earthquake, revealed that 76.8% of the participants stated that the attitude of abandonment of the patient in the operating room is ethically wrong. However, 31.9% of the partic442

There was a statistically significant difference between the two occupational groups although 26.4% (n=32) of the physicians and 39.5% (n=34) of the attorneys proposed that the attitude in question should have legal and criminal liability. We believe that the idea of the physicians is that “There should be criminal sanctions against a situation that does not comply with ethical principles of the society.” is over competed by the idea of the attorneys in that “There should be a legal sanction” in the legal perspective. On the other hand, the reason of that the idea of “There should be a legal sanction” Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Şenel Eraslan et al. Legal and ethical responsibilities of physicians in coercive situations, such as natural disasters

in the answers for the questionnaire from the physician was found to have a less opinion than the attorneys might be because the physicians act more defensive considering that they can face with such situation.

There was no statistical difference between the opinion of the physicians working in surgical branches and working in nonsurgical branches (p>0.05). Although the scenario was more related with the surgical branches, the perspective did not differ statistically depending on the specialty of the physicians.

The mean age and the professional experience were found to be higher for the physicians than for the attorneys. Of the physicians with experience >10 years and <10 years, 91.1% and 67.2%, respectively, found that the attitude in question was ethically wrong. Statistical analyses revealed a significant difference between the two groups. On the other hand, 55.4% and 89.1% of the experienced and inexperienced physicians, respectively, indicated that there should not be a criminal liability with a highly significant difference between the groups. We suggest that the reason of the difference about both ethical and legal liability is due to the fact that inexperienced physicians worry more than experienced ones about what they may face with such situations.

It is difficult to estimate the behavior of the individuals in case of unexpected and life-threatening conditions. The attitude of the physician varies depending on multiple parameters during the surgery where the patient’s life is dependent on the surgeon in cases of coercive situations. Simultaneous and balanced introduction of different principles or rules as the guidance in the ethical dilemmas might explain the reason of the different attitudes of the physicians.[10] It is undeniable that the physicians and other healthcare employees have a right to life as much as the patients in case of a coercive situation, such as natural disasters. In the same way, the attitude of consideration of their own safety by physicians or other healthcare employees may be perceived as protection of the most sacred, the right of life. Within the frame of the proxy agreement, it would not be possible to save or help someone else for the physician without maintaining their own safety.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

In this case, the contract will die out, and this is not the expected responsibility from the health worker.[11] In the scope of the work contract, the responsibility of the health worker is heavier, and the protection of his/her own life should be admitted on the framework of the “right to life.”

In the present study, no complete consensus was detected either between or within two occupational groups about the subject. We presented the evaluation in the forensic medical perspective on the attitude of the physicians in case of coercive situations. In conclusion, we believe that a detailed discussion in the meetings where both occupational groups attend would be beneficial.

Conflict of interest: None declared.

REFERENCES 1. Demir M. The Liability of Doctors under the Medicine Contract [Article in Turkish]. AÜHFD 2008;57:225–52.

2. Koç S, Yorulmaz C. Hekimin yasal sorumlulukları. In: Soysal Z, Çakalır C, editör. Adli Tıp Cilt 3. İstanbul: İstanbul Üniversitesi Basımevi ve Film Merkezi; 1999. p. 45–60.

3. Hakeri H, editör. Tıp hukuku. Ankara: Seçkin Yayıncılık; 2007.

4. Erkan VU. The Obligations of the Principal Excluding the Obligation of Payment the Fee, within the context of Proxy Contracts According to the Turkish Code of Obligations No. 6098 [Article in Turkish]. AÜHFD 2013;62:441–72.

5. Altun G, Coşkun A, Yorulmaz. Yasal değişiklikler sonrası hekim sorumluluğu ve malpraktis. Trakya Üniversitesi Tıp Fakültesi Dergisi 2010;27:7–12.

6. Tıbbi Deontoloji Nizamnamesi. Karar sayısı:4/12578, Kabul tarihi:13.01.1960, Yayın tarihi:19.02.1960.

7. Özaslan A, Kolusayın Ö. Hekimin yasal sorumlulukları. In: Adli Tıp Ders Kitabı. İstanbul: İstanbul Üniversitesi Basım ve Yayınevi Müdürlüğü; 2011. p. 13–39.

8. Aren A. Safety of Patients and Health Workers in Operating Rooms [Article in Turkish]. İstanbul Tıp Dergisi 2008;3:141–5.

9. Öğün B. Ameliyathanede hasta güvenliğinin incelenmesi. [Master Thesis]. Istanbul: Marmara Üniversitesi, Sağlık Bilimleri Enstitüsü; 2008.

10. Yıldırım G, Kadıoğlu S. Etik ve tıp etiği temel kavramları. C.Ü. Tıp Fakültesi Dergisi 2007;29:7–12.

11. Pulat Gözübüyük A. Mücbir sebepler beklenmeyen haller. Ankara; 1977. p. 66.

443

Şenel Eraslan et al. Legal and ethical responsibilities of physicians in coercive situations, such as natural disasters

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Doğal afetler gibi mücbir durumlarda hekimin hukuki ve etik sorumluluğu Dr. Berna Şenel Eraslan,1 Dr. Beytullah Karadayı,1 Dr. İbrahim Eray Çakı,1 Dr. Naciye Aslan,2 Dr. Ende Varlık Tokgözoğlu,1 Dr. Çağlayan Kılıç,3 Dr. Abdi Özaslan,1 Dr. Gürsel Çetin1 İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Adli Tıp Anabilim Dalı, İstanbul Adalet Bakanlığı, Adli Tıp Kurumu, İstanbul 3 İstanbul Medeniyet Üniversitesi, Sosyal Bilimler Enstitüsü, Tıp Hukuku, İstanbul 1 2

AMAÇ: Hekim ile hastası arasındaki ilişkinin temeli vekâlet sözleşmesi hükümlerine tabidir. Gerçekleştirdiği riskli bir ameliyat esnasında şiddetli bir doğal afet (deprem) meydana gelmesi gibi mücbir durumlarda, hekimin takınacağı tutum ve bu eylemi sonucunda hukuki ve etik açıdan sorumluluğu tartışmalıdır. Bu çalışmada ilgili meslek gruplarının bu konu hakkında görüşlerinin ortaya konulması ve bu konunun etik ve yasal zeminde tartışılması amaçlandı.

GEREÇ VE YÖNTEM: Bu çalışma kapsamında oluşturulan anket formları, İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi’nde görevli 121 hekim ve İstanbul Barosu’na kayıtlı 86 avukat olmak üzere toplam 207 gönüllü katılımcı tarafından dolduruldu. Anketlere verilen yanıtlar bilgisayar ortamında SPSS 21.0 programı kullanılarak tanımlayıcı istatistik ve grafik analizi ile değerlendirildi.

BULGULAR: Katılımcıların %76.8’i, hekimin şiddetli bir doğal afet esnasında kendi can güvenliğini düşünerek hastayı terk etmesinin etik açıdan sorun teşkil ettiğini belirtti. Ancak %68.1’i bu davranışından dolayı hekimin herhangi bir cezai yaptırım ile karşılaşmayacağı yönünde görüş bildirdi. Anketi dolduran iki meslek grubunun yanıtları ayrı ayrı değerlendirildiğinde; hekimlerin %26.4’ü, avukatların ise %39.5’i söz konusu fiilin hukuki ve cezai sorumluluğunun bulunduğunu belirtti.

TARTIŞMA: Bu çalışma sonucunda her iki meslek grubunun birbirleri arasında ve kendi içinde bu konu hakkında tam bir görüş birliği içinde bulunmadıkları saptandı. Her iki meslek grubunun birlikte bulunduğu toplantılarda konunun tartışılması ve doğru bir zemine oturtulması gerektiği sonucuna varıldı.

Anahtar sözcükler: Doğal afetler; hekimin etik sorumluluğu; hekimin yasal sorumluluğu; mücbir sebep.

Ulus Travma Acil Cerrahi Derg 2018;24(5):440-444

444

doi: 10.5505/tjtes.2017.32885

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

ORIG I N A L A R T IC L E

Mortality determiners for fall from height cases Muzaffer Akkoca, M.D., Serhat Tokgöz, M.D., Kerim Bora Yılmaz, M.D., Sümeyra Güler, M.D., Melih Akıncı, M.D., Şener Balas, M.D., Harun Karabacak, M.D., Mehmet Saydam, M.D. Department of General Surgery, University of Health Sciences, Dışkapı Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: The aim of the present study was to investigate the role of body mass index (BMI) and trauma severity score systems on the mortality rates of patients undergoing surgery due to falls from height.

METHODS: This retrospective study included 45 consecutive adult patients with multitrauma who were admitted and operated on due to a fall from height between January 2008 and December 2016. Patients were divided into mortality and recovery groups (n=10 and n=35, respectively). The groups were compared in terms of age, gender, weight, cause of the fall, height of the fall, location of the fall, BMI, trauma scores (Injury Severity Score [ISS], New Injury Severity Score [NISS], Glasgow Coma Scale [GCS], Abbreviated Injury Score [AIS], Revised Trauma Score [RTS]), hospital stay, and postoperative complications.

RESULTS: There was no statistically significant difference between the two groups in terms of age, gender, and height or cause of the fall (p>0.05), whereas there was a statistically significant difference with respect to weight and BMI values (p<0.01). A statistically significant difference was determined between the groups in terms of hospital stay and postoperative complications (p<0.01) and ISS, NISS, GCS, AIS, and RTS scores (p<0.05).

CONCLUSION: The effect of weight and BMI on the mortality rate of patients presenting with trauma as a result of a fall from height was objectively demonstrated in the present study.

Keywords: Body mass index; fall from height; mortality; Trauma Score.

INTRODUCTION Trauma is one of the major causes of death among the young population, resulting in approximately 6 million deaths each year.[1] Approximately 80% of mortality between the ages of 15–24 years is caused by trauma.[2] Although a fall from height is more likely to be accidental, it can also be due to suicide or criminal reasons. The causes of falls from height vary in every age group. The severity of trauma depends on many factors, such as the height of the fall, the speed of deceleration, the composition of the impact surface, other objects impacted during the fall, the part of the body initially affected, and individual factors, such as age, body weight, and comorbidities.[3,4] Trauma scoring systems (TSSs) are widely used for cases of falls from height that may have considerably complex

and heterogeneous pathophysiological patterns and different demographic factors, such as age, gender, and etiology.

Methodologically, TSSs evaluate the severity of injury, including the anatomical severity and the level of physiological disorder, and convert the results into numerical data.

These systems can determine the hospital stay and mortality rates, transfer suitable patients to proper facilities at the right time, compare large series, and eventually provide analyses of trauma care outcomes.[5] The purpose of establishing TSSs is to define the objective and comparable criteria for the determination of the severity of an injury.

Anatomical location, physiological parameters, and trauma mechanisms are the three essential criteria to define the severity of an injury and also predict outcome. Moreover, these expedite the evaluation of various combinations of scoring systems.[6]

Cite this article as: Akkoca M, Tokgöz S, Yılmaz KB, Güler S, Akıncı M, Balas Ş, et al. Mortality determiners for fall from height cases. Ulus Travma Acil Cerrahi Derg 2018;24:445-449.

Address for correspondence: Muzaffer Akkoca, M.D. SBÜ Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara, Turkey Tel: +90 312 - 596 23 12 E-mail: muzafferakk@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):445-449 DOI: 10.5505/tjtes.2018.50724 Submitted: 04.12.2017 Accepted: 22.03.2018 Online: 10.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

445

Akkoca et al. Mortality determiners for fall from height cases

The aim of the present study was to investigate patients who had fallen from height and who were operated on immediately due to hemodynamic instability. Evaluation was made of the reason for the fall, the severity of injury, the treatment methods, and the effects of trauma scores, such as Injury Severity Score (ISS), New Injury Severity Score (NISS), Abbreviated Injury Score (AIS), and Revised Trauma Score (RTS), on the overall morbidity and mortality rates of patients with multitrauma who were admitted and underwent surgery in the General Surgery Service.

MATERIALS AND METHODS This retrospective study included a total of 48 consecutive patients with multitrauma resulting from a fall from height who were admitted and operated on between January 2008 and December 2016 in Dışkapı Yıldırım Beyazıt Research and Training Hospital General Surgery Service. The local ethics committee approved the study. The descriptive data of the patients, such as age, gender, weight, reason for the fall, height of the fall, and location of the fall, were analyzed. Three cases with incomplete data were excluded from the study. All the patient records, including primary and secondary surveys, judicial case reports, autopsy reports, clinical findings, and consultation and operation notes were analyzed. Guided by these data, the severity of injury of the head, cervical, maxillofacial, thoracal, abdominal, and extremity was registered, and then body mass index (BMI), ISS, NISS, RTS, AIS, and Glasgow Coma Scale (GCS) were calculated. A record was made of which organs were injured and what type of operations was performed. Patients with blunt abdominal trauma who were operated in the General Surgery Clinic were included in the study. Patients with multitrauma were separated into two groups according to outcome, as exitus (mortality group) and healed cases (recovery group). Statistical comparisons were made between the two groups with respect to demographic variables, BMI, trauma scores (ISS, NISS, GCS, RTS, and AIS), hospital stay (days), and complications.

Statistical Analysis Data obtained in the study were statistically analysed using the IBM SPSS 11.5 software. (Chicago, USA) Mean, standard deviation, median, and minimum and maximum values were given for descriptive statistics related to continuous data, and number and percentage values were given for discrete data.

The Mann–Whitney U test was used for comparison of discharge status (mortality or recovery) with the data obtained by measurement and trauma scores (age, BMI, etc.), and the chi-square test or Fisher’s exact test was used for comparison of data with the cut-off variables.

The statistical power of separating the deceased and the recovered cases by ISS, NISS, AIS, and RTS scores was compared by the area under the receiver operating characteristic (ROC) curve. The best cut-off point was calculated using 446

Youden’s index. A p value of <0.05 was accepted as statistically significant.

Limitations The major limitation of the present study was the inclusion of only fall from height patients operated on by the General Surgery Department and the exclusion of non-operated patients or those who were operated on by other clinics while being followed up by a general surgery department simultaneously. The primary consideration was to choose and evaluate the most vulnerable group for morbidity and mortality who required any urgent surgery at the time of diagnosis due to unstable hemodynamics.

RESULTS Forty-five multitrauma cases were included in the study. Table 1 shows the gender, age, reason for the fall, length of hospital stay, weight, and BMI of the patients.

Table 2 shows the abdominal trauma present in all cases, injury regions, and grade of injuries.

The mean ISS, NISS, GCS, AIS, and RTS scores of all cases were 32±15.8, 35±18.2, 13±2.8, 3.24±0.92, and 7±1.2, respectively. The most common finding due to abdominal trauma was laceration of the spleen (n=24, 53.3%), followed Table 1. Demographic data of patients with abdominal injury

n

%

Gender Male

34

75.6

Female

11

24.4

Etiology Accident

32

71.1

Suicide

13

28.9

19

59.4

Accident origin (n=32) Construction Ladder

7

21.8

Tree

4

12.5

Electricity pylon

2

6.3

Mean±SD

Median (min-max)

Age (year)

37±16.2

32 (17–72)

Weight (kg)

74±10.1

75 (50–95)

Height (cm)

170±6.1

170 (160–185)

Body mass index

25±3.3

24.8 (19.5–37.1)

Height of the fall (m)

9±5.9

8 (2–30)

Hospital stay (days)

13±13.8

10 (1–76)

SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Akkoca et al. Mortality determiners for fall from height cases

Table 2. Other injury regions and grades with abdominal injury of 45 patients Injury regions

n

%

Injury grades, median (min-max)

Head-neck

25 55.6

3 (1–5)

Face

13 28.9

2 (1–3)

Thorax

37 82.2

3 (2–5)

Abdomen

45

100

4 (1–5)

Extremity

32 71.1

3 (1–5)

External

16 35.6

1 (1–4)

Min: Minimum; Max: Maximum.

by laceration of the liver (n=20, 44.4%), laceration of the kidney (n=14, 31.1%), retroperitoneal hematoma (n=7, 15.6%), laceration of the intestinal meso (n=4, 8.9%), injury of the small intestine (n=3, 6.7%), injury of the stomach (n=2, 4.4%), laceration of the urinary bladder (n=2, 4.4%), injury of the colon (n=1, 2.2%), injury of the diaphragm (n=1, 2.2%), and vascular trauma (n=1, 2.2%).

The recovery group included 35 (77%) cases, and the exitus group comprised 10 (23%) cases. There was no statistically significant difference between the two groups in terms of age, gender, cause of the fall, and height of the fall (p>0.05), whereas there was a statistically significant difference with respect to weight and BMI values (p<0.01). The weight and BMI values of the patients in the mortality group were significantly higher than those of the patients in the recovery group. Although there seemed to be higher values of height of the fall in the mortality group, no statistically significant difference was found between the two groups (p>0.05). The hospital stay was significantly shorter, but the rate of postoperative complications was higher in the mortality group than in the recovery group (p<0.01) (Table 3).

There was no difference between the two groups in the distribution of the head and neck, thorax, abdomen, extremity, and external trauma scores (p>0.05). A statistically significant difference was found with respect to the trauma scores of the head and neck, thorax, abdomen, and extremity (p<0.05).

The head and neck, thorax, abdomen, and extremity trauma

Table 3. Comparison of the demographic data of the two groups

Recovery (n=35)

Mortality (n=10)

p*

Mean±SD Median (min-max) Mean±SD Median (min-max)

Age (year)

36.37±15.75

32 (17–72)

39.40±18.52

35.5 (17–70)

0.683

Weight (kg)

72.31±10.19

72 (50–95)

81.0±6.58

85 (70–90)

0.004

Height (cm)

170.49±5.57

170 (160–180)

172.10±8.23

172 (160–185)

0.600

Body mass index

24.81±3.26

24 (19.50–37.10)

27.30±2.92

27.6 (22–33.20)

0.008

8.03±4.64

8 (2–20)

12.80±8.57

13 (3–30)

0.088

16.14±14.34

12 (3–76)

5.0±7.19

1.5 (1–23)

0.000

Height of fall (m) Length of hospital stay (days)

*p<0.05. SD: Standard deviation; Min: Minimum; Max: Maximum.

Table 4. Comparison of the trauma scores of the two groups

Recovery (n=35)

Mortality (n=10)

p*

Mean±SD Median (min-max) Mean±SD Median (min-max)

Injury Severity Score

28.51±12.39

27 (10–59)

45.30±20.19

44.5 (20–75)

0.023

New Injury Severity Score

31.57±15.77

27 (10–75)

49.10±20.71

46.5 (20–75)

0.021

Glascow Coma Scale

14.0±1.78

15 (8–15)

10.70±4.37

12.5 (4–15)

0.019

Revised Trauma Score

7.45±0.82

7.84 (5.15–7.84)

6.14±1.76

6.35 (3.63–7.84)

0.028

Abbreviated Injury Score

2.92±0.88

3 (1–5)

4.02±0.67

4 (1–5)

0.018

- Head and neck

2.79±0.96

2 (1–4)

3.43±1.27

4 (1–5)

0.034

- Thorax

2.76±0.79

3 (2–5)

3.50±1.07

4 (2–5)

0.073

- Abdomen

3.31±0.77

3 (1–5)

4.40±0.52

4 (4–5)

0.000

- Extremity

3.23±0.95

3 (1–5)

4.33±0.82

4 (3–5)

0.019

*p<0.05. SD: Standard deviation; Min: Minimum; Max: Maximum.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

447

Akkoca et al. Mortality determiners for fall from height cases

scores were significantly higher in the mortality group. There was a significant difference between the groups in terms of ISS, NISS, GCS, AIS, and RTS scores (p<0.05) (Table 4).

after emergency surgery was analyzed. It has been concluded that obesity is associated with increased morbidity, whereas overweight and class I obesity are protective.[17]

DISCUSSION

In the current study, the hospital stay in the mortality group was significantly lower, and the complication rate was significantly higher than those in the recovery group. The head and neck, thorax, abdomen, and extremity trauma grades were significantly higher in the mortality group. Ground contact in a fall from height usually occurs against the head and chest as these are the lowest points of gravity of the human body, and craniocerebral injuries are one of the major causes of mortality.[18] In falls from average height, the frequency of impacts on the chest region increases.[12,19] Içer et al.[4] reported that hemopneumothorax and subarachnoid hemorrhage are the most important independent risk factors affecting mortality.

Abdominal injuries are the third most common cause of death in trauma-related incidents.[7] An early diagnosis followed by the appropriate treatment can reduce mortality rates by up to 50%.[8] The timing in the evaluation of trauma cases, using accurate imaging methods, trauma algorithms, and scoring systems are important in emergency departments, although they can change over time.[9,10] A fall from height is defined as a free vertical fall from a height of ≥2 m.[11] Patients presenting with fall from height are also susceptible to deceleration injuries as well as direct impact injuries. The kinetic energy (KE=1/2 mV2) of the fall depends on body mass and height.[12] Similarly, as the height increases, the free body mass accelerates due to gravity (v=√ (2gh)), and its velocity increases.[13] The mortality rate reported in patients with fall from height depends on the height of the fall and the methodology of the study. Higher mortality rates have been reported in a series where patients have been lost at the scene or during transfer.

Liu et al.[14] reported a mortality rate of 22.7% in a series of patients falling from a height of >6 m. In addition, Lapostolle et al.[3] reported a 34% mortality rate in patients falling from >3 m. However, in another study, the hospital mortality rate was reported as 9.6% for falls from >6 m.[15] In the current study, there was no statistically significant difference with respect to the height of the fall. However, it may be that the average height of the fall in both groups was above the critical height of 6 m.

Literature has shown that major abdominal injuries are rare, but solid organ injuries (liver, spleen, and kidney) are particularly associated with high morbidity and mortality rates.[11] In an autopsy series by Jagannatha et al.,[16] it was reported that liver and spleen injuries occur at heights >24 m regardless of their effect type. Abdominal injuries are associated with a poor outcome, but it has been reported that survival may improve with immediate surgical exploration in hemodynamically unstable patients.[11] In the current study, which similarly included hemodynamically unstable patents, the injuries recorded were mostly from spleen, liver, and renal laceration.

When the results of the present study are evaluated, the effect of weight and BMI on mortality in patients with fall from height can be clearly seen. These parameters were considered to have an effect on the kinetic energy generated during the fall from height.[12] Obese patients appear to have a higher risk of mortality after a fall from height; therefore, the present study may provide data for stronger preventive measures against falls for obese patients. On the other hand, recently, the effect of BMI on over a hundred thousand patients 448

TSSs are commonly used to determine the severity of any trauma. In the evaluation of trauma scores, the association of ISS with increasing height variable has been previously reported.[11] Beale et al. showed clearly numerically that an ISS of ≥50 is uniformly associated with death. Eryılmaz et al.[20] compared trauma scores in terms of fall from height and reported that the areas under the curve are 0.910 for ISS and 0.915 for NISS in ROC analysis. Dickinson et al.[12] also reported that the height of the fall is correlated with the ISS score. Liu et al.[14] stated that an ISS score of ≥16 in patients falling from a height of >6 m is one of the factors significantly correlated with mortality in univariate analysis, and a head/neck AIS of ≥4 is independently correlated with the final mortality rate in multivariate analysis. In addition, in blunt abdominal trauma, the association with mortality of high ISS values due to gastrointestinal system injuries has been described.[21] There have been many recent developments in radiological and laboratory evaluation methods for patients with multiple trauma, and these methods are expected to be increasingly helpful for quick decision-making and the management of patients with trauma. Based on these evaluations, scoring systems and treatment algorithms have been developed to be able to approach patients with trauma in the most appropriate way. The factors examined in the present study can be considered useful for the development of algorithms and standardization. It is important to define the cut-off values of injury scores and, thereby, identify high-risk groups in order to establish more extensive preventive measures if possible and to make triage decisions for early transfer, early surgery, and other extreme situations requiring difficult decisions.

Many factors determine the severity of injury and mortality in a fall from height.

In the present study, the importance of weight and BMI was examined on mortality rate. However, as different age and gender groups are affected differently by each of these variables, there are still many issues that require further investiUlus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Akkoca et al. Mortality determiners for fall from height cases

gation. Therefore, there is a need for multicentered studies with extensive case series in order to determine the factors affecting morbidity and mortality and to be able to generate algorithms and guidelines based on the diagnosis, follow-up, and treatment processes of the patients.

Conflict of interest: None declared.

M. Radiological management of patients with multiple trauma: history and current practice [Article in Spanish]. Radiologia 2010;52:105–14.

10. van Schuppen J, Olthof DC, Wilde JC, Beenen LF, van Rijn RR, Goslings JC. Diagnostic accuracy of a step-up imaging strategy in pediatric patients with blunt abdominal trauma. Eur J Radiol 2014;83:206–11.

11. Beale JP, Wyatt JP, Beard D, Busuttil A, Graham CA. A five year study of high falls in Edinburgh. Injury 2000;31:503–8.

12. Dickinson A, Roberts M, Kumar A, Weaver A, Lockey DJ. Falls from height: injury and mortality. J R Army Med Corps 2012;158:123–7.

REFERENCES 1. Curry N, Davis PW. What’s new in resuscitation strategies for the patient with multiple trauma? Injury 2012;43:1021–8.

2. Güneş Tatar İ, Yilmaz KB, Ergun O, Balas Ş, Akinci M, Deryol R, et al. The effect of clinical, laboratory and radiologic results on treatment decision and surgical results in patients admitted to the emergency department with blunt abdominal trauma due to traffic accident [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2015;21:256–60.

3. Lapostolle F, Gere C, Borron SW, Pétrovic T, Dallemagne F, Beruben A, et al. Prognostic factors in victims of falls from height. Crit Care Med 2005;33:1239–42.

4. Içer M, Güloğlu C, Orak M, Ustündağ M. Factors affecting mortality caused by falls from height. Ulus Travma Acil Cerrahi Derg 2013;19:529–35.

5. Wisner DH. History and current status of trauma scoring systems. Arch Surg 1992;127:111–7.

6. Bond RJ, Kortbeek JB, Preshaw RM. Field trauma triage: combining mechanism of injury with the prehospital index for an improved trauma triage tool. J Trauma 1997;43:283–7.

7. Shojaee M, Faridaalaee G, Yousefifard M, Yaseri M, Arhami Dolatabadi A, Sabzghabaei A, et al. New scoring system for intra-abdominal injury diagnosis after blunt trauma. Chin J Traumatol 2014;17:19–24.

8. Chardoli M, Rahimi-Movaghar V. Analysis of trauma outcome at a university hospital in Zahedan, Iran using the TRISS method. East Afr Med J 2006;83:440–2.

9. Martí De Gracia M, Artigas Martín JM, Vicente Bártulos A, Carreras Aja

13. Kepler CK, Nho SJ, Miller AN, Barie PS, Lyden JP. Orthopaedic injuries associated with fall from floor forty-seven. J Orthop Trauma 2009;23:154–8.

14. Liu CC, Wang CY, Shih HC, Wen YS, Wu JJ, Huang CI, et al. Prognostic factors for mortality following falls from height. Injury 2009;40:595–7.

15. Velmahos GC, Demetriades D, Theodorou D, Cornwell EE 3rd, Belzberg H, Asensio J, et al. Patterns of injury in victims of urban free-falls. World J Surg 1997;21:816–20.

16. Jagannatha SR, Pradeep Kumar MV, Naveen Kumar T, Ananda K, Venkatesha VT. Injuries due to fall from height – a retrospective study.

Journal of Forensic Medicine and Toxicology 2010;27:47–50.

17. Benjamin ER, Dilektasli E, Haltmeier T, Beale E, Inaba K, Demetriades D. The effects of body mass index on complications and mortality after emergency abdominal operations: The obesity paradox. Am J Surg 2017;214:899–903.

18. Kusior ME, Pejka K, Knapik M, Sajuk N, Kłaptocz S, Konopka T. Analysis of the nature of injuries in victims of fell from height. Arch Med Sadowej Kryminol 2016;66:106–24.

19. Risser D, Bönsch A, Schneider B, Bauer G. Risk of dying after a free fall from height. Forensic Sci Int 1996;78:187–91.

20. Eryılmaz M, Durusu M, Menteş Ö, Özer T, Kılıç S, Ersoy G, et al. Comparison of trauma scores for adults who fell from height as survival predictivity. Turk J Med Sci 2009;39:247–52.

21. Al-Hassani A, Tuma M, Mahmood I, Afifi I, Almadani A, El-Menyar A, et al. Dilemma of blunt bowel injury: what are the factors affecting early diagnosis and outcomes. Am Surg 2013;79:922–7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yüksekten düşme olgularında mortaliteye neden olan faktörler Dr. Muzaffer Akkoca, Dr. Serhat Tokgöz, Dr. Kerim Bora Yılmaz, Dr. Sümeyra Güler, Dr. Melih Akıncı, Dr. Şener Balas, Dr. Harun Karabacak, Dr. Mehmet Saydam SBÜ Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Bu çalışmada vücut kitle indeksi (VKİ) ve Travma Derecesi Skorlama Sistemi’nin yüksekten düşme nedeniyle ameliyat edilen hastaların mortalite oranları üzerindeki rolü araştırıldı.

GEREÇ VE YÖNTEM: Bu geriye dönük çalışma, Ocak 2008 ile Aralık 2016 tarihleri arasında yüksekten düşme nedeniyle başvuran ve ameliyat edilen, çoklu travmalı 45 ardışık erişkin hastayı içermiştir. Hastalar mortalite ve yaşayan gruplarına ayrılmıştır (n=10, n=35, sırasıyla). Gruplar yaş, cinsiyet, kilo, düşme nedeni, düşme yüksekliği, düşme yeri, VKİ, Travma Skorları (Injury Severity Score [ISS], New Injury Severity Score [NISS], Glasgow Coma Scale [GCS], Abbreviated Injury Score [AIS], Revised Trauma Score [RTS]), hastanede kalış süresi ve ameliyat sonrası komplikasyonlar açısından karşılaştırıldı.

BULGULAR: Her iki grup arasında yaş, cinsiyet, boy veya düşme nedeni açısından istatistiksel olarak anlamlı fark bulunmazken (p>0.05), kilo ve VKİ değerleri açısından istatistiksel olarak anlamlı fark saptandı (p<0.01). Gruplar arasında hastanede kalış süresi ve ameliyat sonrası komplikasyonlar açısından (p<0.01), ISS, NISS, GCS, AIS ve RTS skorları açısından istatistiksel olarak anlamlı fark saptandı (p<0.05).

TARTIŞMA: Bu çalışmada, yüksekten düşme sonucu travma ile başvuran hastaların vücut ağırlığı ve VKİ’nin mortalite üzerine etkisi objektif olarak gösterilmiştir.

Anahtar sözcükler: Mortalite; Travma Skoru; vücut kitle indeksi; yüksekten düşme.

Ulus Travma Acil Cerrahi Derg 2018;24(5):445-449

doi: 10.5505/tjtes.2018.50724

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

449

ORIG I N A L A R T IC L E

Retrospective analyses of high-energy explosive devicerelated injuries of the ear and auricular region: experiences in an operative field hospital emergency room Mehmet Burak Aşık, M.D.,

Murat Binar, M.D.

Department of Otolaryngology and Head&Neck Surgery, Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: With the changing conditions of terrorism, particularly in urban areas, high-energy explosive devices such as improvised explosive devices (IEDs) and projectile missiles (PMs) are frequently used. Traumas caused by these devices particularly affect the maxillofacial region and typically lead to otologic problems. In this study, we aimed to evaluate otologic complaints, otoscopic and auricular examinations, and tuning-fork tests of patients who were exposed to high-energy blast-related injuries and perform a comparison between trauma patients injured by IEDs and PMs. METHODS: The medical data of patients admitted to an operational field hospital emergency room with injuries related to highenergy explosive devices such as IEDs and PMs between July 27, 2015 and July 22, 2016 was reviewed. The hearing impairment, tinnitus, otologic examination, auricular region examination, and tuning-fork tests of all patients were evaluated. The otologic evaluation records of the patients (n=86) were evaluated using a scoring system established by the authors. The patients were categorized into two groups according to the device causing the injury: IEDs in group I and PMs in group II. RESULTS: A total of 241 combatants were injured by high-energy explosive devices. All patients were male with a mean age of 30.2 years (range, 20–54). Of these, 86 had hearing impairments that were detected by tuning-fork tests. Of those, 50 were injured by IEDs and 36 by PMs. Of the 86 patients, 18 had traumatic tympanic membrane perforation, and of those, 6 patients were injured by IEDs and 12 by PMs. Further, 68 of the 86 patients had sensorineural hearing loss, and of those, 44 were injured by IEDs and 24 by PMs. There was a statistically significant difference between the IED and PM groups according to otologic evaluation score (p=0.044).

CONCLUSION: This study demonstrates that PMs can have a large impact on the human ear and may cause more severe otologic manifestations among combatants than those caused by IEDs. The early and accurate evaluation of patients exposed to high-energy explosive devices in an operational field is important for the appropriate management of these patients.

Keywords: Ear; high-energy explosive devices; otology; trauma; tuning-fork tests.

INTRODUCTION With the changing nature of asymmetrical warfare, high-energy explosive device traumas are increasingly being seen.[1] High-energy explosive devices such as improvised explosive devices (IEDs) and projectile missiles (PMs) are commonly employed by terrorist groups in urban areas, particularly at close range.[1,2] An IED is a “homemade” bomb and destructive device that is used to destroy and distract; therefore,

IEDs are occasionally used by terrorists and suicide bombers.

A PM is a self-propelled rocket that is fired from a weapon and cannot be adjusted after launch. Both devices particularly cause maxillofacial region traumas and can lead to ear problems because of their high acoustic energy. Therefore, combatants exposed to close range explosives may have otologic problems as well as other systemic morbidities. Most of the injuries observed after high-explosive detonations comprise conventional blunt, penetrating, and thermal trauma.[2]

Cite this article as: Aşık MB, Binar M. Retrospective analyses of high-energy explosive device-related injuries of the ear and auricular region: experiences in an operative field hospital emergency room. Ulus Travma Acil Cerrahi Derg 2018;24:450-455.

Address for correspondence: Mehmet Burak Aşık, M.D. Gülhane Eğitim ve Araştırma Hastanesi, KBB ve Baş-Boyun Cerrahisi Kliniği, Keçiören, 06018 Ankara, Turkey Tel: +90 312 - 304 57 10 E-mail: burock312@yahoo.com Ulus Travma Acil Cerrahi Derg 2018;24(5):450-455 DOI: 10.5505/tjtes.2017.60649 Submitted: 19.06.2017 Accepted: 11.12.2017 Online: 10.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

450

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aşık et al. High-energy explosive device-related otologic injuries

Depending on the duration and strength of the sound pressure affecting the human ear, isolated or combined otologic manifestations, such as ear drum perforation, interruption of the middle ear ossicle chain, and inner ear damage, may occur.[3,4] Otoscopy, pure tone audiometry, measurement of otoacoustic emissions, radiological assessment, and neurotologic evaluation are used to determine the severity of the trauma. With prompt and adequate therapy, permanent hearing loss can be minimized.[2,3] However, many combat areas are far away from tertiary hospitals, and nowadays, health care is provided by operational field hospitals in most countries. Although the transportation of patients can be easily arranged, the first doctor in charge at an operational field hospital is responsible for the evaluation and management of the patients.

The early and accurate assessment of injured patients in an operational field hospital is a vital part of the care for patients with otologic trauma. Audiological assessment is critical in the evaluation of acoustic trauma patients, but there may not be an audiological unit in operation field hospitals. Therefore, only two methods exist for the evaluation of such patients in these hospitals: otologic examination and tuning-fork tests.

In this study, we aimed to evaluate otologic complaints, otoscopic and auricular examinations, and tuning-fork tests of combatants who were exposed to high-energy blast-related injuries in the operational field. We also aimed to share our experience that was gained in the operational field hospital.

We performed a comparison between trauma patients injured by IEDs and PMs based on otologic assessment.

MATERIALS AND METHODS Patient Selection Review board approval was obtained for this retrospective study (KAEK-15-1103/13.04.2016). Patients who had been admitted to an operational field emergency room because of exposure to and injury by high-energy explosive devices between July 2015 and July 2016 were retrospectively enrolled. Patients were excluded if they had more severe systemic morbidities other than ear problems or had undergone emergency surgical intervention because of other fatal reasons. Based on their exposure to different explosive devices, the study population was divided into two subgroups: the IED group and the PM group. All patients were asked if they had any otologic complaints such as hearing loss and tinnitus.

Additionally, they were asked if they had further complaints such as vertigo. However, none of them had vertigo.

Tuning Fork Tests After otoscopic examination and temporal region evaluation, tuning-fork tests (Weber and Rinne tests) were performed in the frequency range of 256–512 Hz (We had only two kinds of tuning-fork instruments in the operational field Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

hospital, which were at 256 and 512 Hz). All the tuning tests were performed by the author (M.B.A.) who was an otolaryngologist and head-neck surgeon in an operational field hospital. The Weber test was used to detect unilateral conductive and unilateral sensorineural hearing loss. A vibrating fork was placed over the forehead/vertex/chin of the patient, and the patient was instructed to indicate the ear in which sound could be better heard. In normal ear and in bilateral equally hearing loss, the sound would be heard at the midline. A patient with a unilateral (one-sided) conductive hearing loss would hear the tuning fork loudest in the affected ear. This is because the conduction problem masks the ambient noise of the environment, while the wellfunctioning inner ear detects the sound via the bones of the skull, causing it to be perceived as a louder sound than in the unaffected ear. In unilateral sensorineural hearing loss or unilateral total hearing loss, the sound would be heard best in the unaffected ear. Therefore, this test is very useful in patients with hearing that is different between the two ears. It cannot confirm normal hearing because it does not measure sound sensitivity in a quantitative manner. Hearing defects affecting both ears equally, e.g., bilateral equally hearing loss, would produce an apparently normal test result. Following the Weber test, the Rinne test was applied. The Rinne test is used to compare air conduction with bone conduction thresholds. Under normal circumstances, air conduction is better than bone conduction. The tuning fork should be struck against the elbow or knee of the patient to vibrate.

While striking, care must be taken that the strike is made at the junction of the upper 1/3 and lower 2/3 of the fork.

This is the maximum vibratory area of the tuning fork. It should not be struck against a metallic object because it can cause overtones. As soon as the fork begins to vibrate, it is placed at the mastoid process of the patient. The patient is advised to signal when he (she) stops hearing the sound.

As soon as the patient signals that he is unable to hear the sound anymore, the vibrating fork is immediately transferred close to the external auditory canal. In patients with normal hearing, he (she) should be able to hear the fork as soon as it is transferred to the front of the ear. This result is known as positive Rinne test (air conduction is better than bone conduction). In case of conductive hearing loss, the patient will not be able to hear the fork sufficiently as soon as it is transferred to the front of the ear (bone conduction is better than air conduction). This is known as negative Rinne test. If the patient is suffering from profound or total unilateral hearing loss (i.e., a “dead” ear), the sound would still be heard through the bone conduction of opposite ear, but will not be heard when the tuning fork is transferred to the external auditory canal of affected ear. This condition leads to a false negative Rinne. If sensorineural hearing loss exists, both bone and air conduction time decreases, so the ratio of air/bone conduction time remains the same. This is called pathological positive Rinne. Tuning-fork test results are summarized in Table 1. Based on these tests, the type of hearing loss was determined.

451

Aşık et al. High-energy explosive device-related otologic injuries

Table 1. Explanations of tuning-fork tests Test

Normal hearing

Conductive hearing loss

Sensorineural hearing loss

Total hearing loss

Rinne

AC time > BC time

AC time < BC time

AC time > BC time;

BC+ (heard from opposite ear)

(positive Rinne)

(negative Rinne)

but both decrease

AC- (sound cannot be heard)

Weber

(pathological positive Rinne)

(false negative Rinne)

Sound is heard

Sound is heard better

Sound is heard better

Sound is heard in good ear

at midline

in bad ear

in good ear

Otologic Examination and Scoring System According to the otoscopic examinations and tuning-fork tests, the severity of the otologic situation of the patients was assessed via a scoring system described as follows: complaint of hearing loss (1 point), complaint of tinnitus (1 point), conductive or sensorineural hearing loss detected by tuning-fork tests (1 point), tympanic membrane perforation (1 point), and auricula defect (1 point). As a result of this scoring system, a patient could be given a maximum of 5 points. A comparison was made between the IED and the PM groups.

After the appropriate first treatment application, the patients were referred to a tertiary center for audiological tests, radiologic assessment, and possible medical/surgical treatment, due to lack of an audiological unit in the operation field hospital. A patient exposed to IED trauma is shown in Figure 1.

Statistical Analysis Statistical analyses were performed using SPSS for Win. Ver.15.0 (SPSS Inc., Chicago, IL., USA). After the variables were investigated to determine whether they were normally distributed, the Mann–Whitney U test was used for the comparison of continuous variables between two groups. Significance was defined as p<0.05.

RESULTS A total of 281 combatants were injured by high-energy explosive devices. All patients were male, with a mean age of 30.2 years (range, 20–54). Of those, 40 combatants could not be

Figure 1. Auricular defect due to IED trauma.

452

Table 2. The complaints and examination findings in the groups

IED (n=50)

PM (n=36)

n (%)

n (%)

50 (100)

36 (100)

Complaints of hearing loss Complaints of tinnitus

42 (84)

30 (83)

Hearing loss (tuning-fork tests)

50 (100)

36 (100)

Tympanic membrane perforation

6 (12)

12 (33)

Auricula defects

2 (4)

10 (28)

IED: Improvised explosive device; PM: Projectile missile.

examined owing to their critical vital and clinical conditions in the emergency room. Of the remaining 241 patients with otologic complaints, 133 were IED-injured combatants and 108 were PM-injured combatants. Of 241, 86 had both hearing impairment complaint and otologic findings. Of those, 50 were injured by IEDs and 36 were injured by PMs. The flowchart showing the management of the patients is shown in Figure 2.

After brief anamnesis and recording hearing impairment and tinnitus complaints, all patients underwent otoscopic examination. Eighteen patients had traumatic tympanic membrane perforation, and of those, 6 patients were injured by IEDs and 12 by PMs. Twelve patients had auricular defects, and of those, 2 patients were injured by IEDs and 10 by PMs. All the patients with auricula defects were injured partially and none of them had external auditory canal defect. In all patients with traumatic tympanic membrane perforation (n=18), conductive hearing loss was also detected by tuning-fork tests. Of those, 6 patients were injured by IEDs and 12 by PMs. Sixtyeight out of 86 had sensorineural hearing loss that was detected by tuning-fork tests. Of those, 44 had IED injury and 24 had PM injury (Table 2).

The mean IED (n=50) otologic evaluation score was 3±0.69, and the median was 3. The mean PM (n=36) otologic evaluation score was 3.44±1.02, and the median was 3. There was a statistically significant difference between the IED and PM groups based on the otologic evaluation score (p=0.044).

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aşık et al. High-energy explosive device-related otologic injuries

Patinets admitted to operational field emergency room due to be exposed by high-emergy explosives (n=281) - Patinets with more severe systemic morbidities other than ear problems (n=18) - Patients undergoing emengency surgical interventation due to other fatal reasons (n=22) Remaning patients having otologic complaints (n=241)

Improvised explosive devices (n=133)

Otologic finding and symtoms (+) (n=50)

Otologic finding and symtoms (–) (n=83)

Projectile missiles (n=108)

Otologic finding and symtoms (+) (n=36)

Otologic finding and symtoms (–) (n=72)

Tuning-fork tests

SNHL (n=44)

CHL (n=6)

SNHL (n=24)

CHL (n=12)

Figure 2. Flowchart of enrolled patients according to otologic examination and tuning-fork tests. SNHL: Sensorineural hearing loss; CHL: Conductive hearing loss.

The findings of tympanic membrane perforation and auricula defect were more common in the PM than in the IED group (Table 2).

DISCUSSION Given the outcomes of this study, high-energy explosive devices such as IEDs and PMs can cause various degrees of otologic injuries among combatants. Moreover, otologic trauma caused by PMs appears to be more severe compared with that caused by IEDs. Although both PMs and IEDs are categorized as high-energy explosives, their use in urban terrorist attacks varies from each other. IED detonations occur frequently when combatants are deployed in a military vehicle or behind a defilade position.[5] Moreover, these two high-energy explosives are frequently used in urban areas by terrorist groups.[5,6] IEDs that are trapped on the roadside or in a wall are detonated while combatants are walking or entering a building, or while their vehicles are crossing. Therefore, a combatant is exposed to a blast behind a protected area or in an armored vehicle.[7] Most of the time, mortal injuries occur when a Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

combatant is exposed directly to the detonation.[5,8] PMs are frequently used in two different ways; toward the area where combatants typically exist or directly to combatants during planned terrorist attacks. Therefore, there may be more detonation effects on combatants and their surroundings.

Although PMs create lower detonation energies than IEDs, the detonation of a PM directly affects the combatant.[8,9] As expected from the given information, the statistical analysis also revealed that more otologic morbidity was observed by PM detonation among the combatants.

According to outcomes of this study, the number of patients experiencing sensorineural hearing loss due to the effect of acoustic trauma after detonation was higher than those experiencing conductive hearing loss. Hearing impairment and tinnitus complaints due to IED injuries were observed much more compared with PMs. However, in injuries caused by PMs, there were more findings in the otoscopic and auricular examinations. Although it was not confirmed statistically, we also observed that tympanic membrane perforations and auricular defects occurred more frequently in combatants injured by PM explosions.

453

Aşık et al. High-energy explosive device-related otologic injuries

Emergency service assessment is always the most critical step in the evaluation of trauma patients, and morbidity is significantly reduced in these patients, who are evaluated correctly without wasting time.[5,9] In the literature search, we found several studies that evaluated trauma patients exposed to blastic traumas using audiological assessment.[3,10,11] Because of the absence of audiological units in the operation field hospital, we were unable to evaluate the patients with pure tone audiogram. Therefore, we were able to investigate the pre-diagnosis of patients with or without the findings of otoscopic examination and tuning-fork tests. Transportation to tertiary hospitals was promptly performed to provide appropriate treatment and audiological assessment for these patients. The use of tuning-fork tests as a first-step instrument for detection of hearing levels is fairly limited nowadays owing to the easy accessibility of audiometry in hospitals; however, we recommend their routine use in cases where physicians have no access to audiological units and quick evaluation for triage is required.

The limitations of this study included the lack of ability to confirm the findings with the radiological and audiological records of the trauma patients. The data analyzed for this study showed that a few primary records of the patients were insufficient for forensic and medical evaluations. Moreover, there was a lack of data on the post-injury complications and comprehensive treatment of these patients.

The results of this study are important for operational field doctors as well as combatants and their commanders. The doctors are responsible for diagnosis and appropriate treatment. Owing to the lack of audiological units and otologic equipment in most of these hospitals, doctors and commanders should take precautions for early transportation of injured patients. Although ballistic shielding for ears is considered sufficient for combatants to avoid otologic morbidity, its utility in operational fields should be discussed. Further studies and investigations on the protection of ears in combat areas should be performed by ballistic experts and otolaryngologists.

Conclusion This study demonstrated that PMs can have a larger impact on the human ear and may cause more severe otologic manifes-

454

tations among combatants than IEDs. The early and accurate evaluation and appropriate treatment of patients exposed to otologic injury in an operational field should be of utmost importance. Otolaryngologists working in operational field hospitals should use all possible instruments to reach an early diagnosis regarding the otologic condition and provide the transportation of these patients as early as possible.

Conflict of interest: None declared.

REFERENCES 1. Martí M, Parrón M, Baudraxler F, Royo A, Gómez León N, Alvarez-Sala R. Blast injuries from Madrid terrorist bombing attacks on March 11, 2004. Emerg Radiol 2006;13:113–22.

2. Aşık MB, Akay S, Eksert S. Analyses of combat-related injuries to the maxillofacial and cervical regions and experiences in an operational field hospital. Ulus Travma Acil Cerrahi Derg 2018;24:56–60.

3. Wightman JM, Gladish SL. Explosions and Blast Injuries. Ann Emerg Med 2001;37:664–78.

4. Mrena R, Pääkkönen R, Bäck L, Pirvola U, Ylikoski J. Otologic consequences of blast exposure: a Finnish case study of a shopping mall bomb explosion. Acta Otolaryngol. 2004;124:946–52.

5. Garth RJN. Blast injury of the ear. In: Cooper GJ, Dudley HAF, Gann DS, Little RA, Marynard RL, editors. Scientific Foundations of Trauma.

Oxford: Butterworth-Heinemann; 1997. p. 225–35.

6. Salinas NL, Brennan J, Gibbons MD. Massive facial trauma following improvised explosive device blasts in Operation Iraqi Freedom. Otolaryngol Head Neck Surg 2011;144:703–7.

7. Peleg K, Aharonson-Daniel L, Michael M, Shapira SC; Israel Trauma Group. Patterns of injury in hospitalized terrorist victims. Am J Emerg Med 2003;21:258–62.

8. Ramasamy A, Masouros SD, Newell N, Hill AM, Proud WG, Brown KA, et al. In-vehicle extremity injuries from improvised explosive devices: current and future foci. Philos Trans R Soc Lond B Biol Sci 2011;366:160–70.

9. Brennan J. Head and neck trauma in Iraq and Afghanistan: different war, different surgery, lessons learned. Laryngoscope 2013;123:2411–7.

10. Wordsworth M, Thomas R, Breeze J, Evriviades D, Baden J, Hettiaratchy S. The surgical management of facial trauma in British soldiers during combat operations in Afghanistan. Injury 2017;48:70–4.

11. Ballivet de Régloix S, Crambert A, Maurin O, Lisan Q, Marty S, Pons Y. Blast injury of the ear by massive explosion: a review of 41 cases. J R Army Med Corps 2017;163:333–8.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aşık et al. High-energy explosive device-related otologic injuries

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kulak ve aurikular bölgenin yüksek enerjili patlayıcılar kaynaklı yaralanmalarının geriye dönük analizi: Operasyon saha hastanesi acil servis deneyimleri Dr. Mehmet Burak Aşık, Dr. Murat Binar Gülhane Eğitim ve Araştırma Hastanesi, Kulak Burun Boğaz ve Baş-Boyun Cerrahisi Kliniği, Ankara

AMAÇ: Terörizmin koşulları değiştikçe, özellikle kentsel alanlarda, el yapımı patlayıcılar gibi yüksek enerjili patlayıcı maddeler sıklıkla kullanılmaktadır.

Bu travmalar özellikle maksillofasiyal bölgeyi etkiler ve genellikle otolojik problemler yaratırlar. Bu çalışma, yüksek enerjili patlamayla ilişkili yaralanmalara maruz kalan hastaların otolojik şikayetlerini, otoskopik ve auriküler muayene ve diyapozon testlerini değerlendirmeyi ve otolojik değerlendirme skorlarına dayanarak el yapımı patlayıcılar (İED) ve rokete (PM) bağlı yaralanan travma hastaları arasında bir karşılaştırma yapmayı amaçlamıştır.

GEREÇ VE YÖNTEM: 27 Temmuz 2015 ile 22 Temmuz 2016 tarihleri arasında el yapımı patlayıcı EYP ve roket PM nedeniyle yaralanan ve operasyonel saha hastanesi acil servisine başvuran 241 hastanın tıbbi verileri gözden geçirildi. Tüm hastalar için işitme bozukluğu, kulak çınlaması şikayetleri, otolojik muayene, aurikuler bölgede muayene ve diyapozon testleri yapıldı ve otolojik problemi olan hastaların (n=86) otolojik değerlendirme skoru kayıtları değerlendirildi. Hastalar yaralanmaya neden olan cihaza göre iki gruba ayrıldı: Grup I’de İED, grup II’de PM’ler.

BULGULAR: İki yüz kırk bir savaşçı, yüksek enerjili patlayıcılarla yaralanmıştı. Tüm hastalar erkekti ve yaş ortalaması 30.2 idi (aralık 20–54). İki yüz kırk birinden 86’sında işitme şikayeti mevcuttu. Bunların 50’sinin İED tarafından yaralanması ve 36’sı PM tarafından yaralanmıştı. Seksen altı hastanın 18’inde travmatik timpanik membran perforasyonu vardı ve altı hasta İED, 12 hasta PM nedeniyle yaralanmıştı. Seksen altı hastanın 68’inde sensorinöral işitme kaybı vardı ve bu hastaların 44’ünde İED yaralanması ve 24’ünde PM yaralanması vardı. Otolojik değerlendirme skoruna göre İED ve PM grupları arasında istatistiksel olarak anlamlı farklılık vardı (p=0.044).

TARTIŞMA: Bu çalışma, roket yaralanmalarının insan kulağında daha büyük bir etkiye neden olabileceğini ve travma hastaları arasında el yapımı patlayıcılara göre daha şiddetli otolojik bulgular yarattığını gösterdi. Operasyonel saha hastanesi gibi acil müdahale alanlarında otolojik yaralanmaya maruz kalan hastaların erken ve doğru değerlendirilmesi ve uygun tedavisi çok önemlidir.

Anahtar sözcükler: Diyapozon testleri; kulak; otoloji; travma; yüksek enerjili patlayıcılar.

Ulus Travma Acil Cerrahi Derg 2018;24(5):450-455

doi: 10.5505/tjtes.2017.60649

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

455

ORIG I N A L A R T IC L E

Clinical evaluation of negative-pressure wound therapy in the management of electrical burns Kemal Eyvaz, M.D., Metin Kement, M.D., Salim Balin, M.D., Hakan Acar, M.D., Fikri Kündeş, M.D., Alev Karaoz, M.D., Osman Civil, M.D., Mehmet Eser, M.D., Levent Kaptanoglu, M.D., Selahattin Vural, M.D., Nejdet Bildik, M.D. Department of General Surgery, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: In this study, we aimed to evaluate the clinical efficacy and safety of negative-pressure wound therapy (NPWT) in the treatment of the patients with electrical burns.

METHODS: This study was retrospectively performed using a database placed prospectively in the burn center of our hospital.

All consecutive patients with electrical burns treated using NPWT at our center between August 2008 and December 2012 were included. The treatment results in our study were grouped as successful or unsuccessful considering the treatment objectives in accordance with therapy indications.

RESULTS: In total, 39 patients were included in our study; of them, 36 (92.3%) were men. The average age was 34.9±9.8 years (range, 17–63 years). The majority of the patients in our study (92.3%) had been exposed to high voltage electricity. The mean total burned body surface area (TBSA) was 19.3±9.8 (range, 4–44). Six patients (15.4%) had TBSAs ≥30%, 31 (79.5%) had third degree burns, and 8 (20.5%) had fourth degree burns. In our study, indications of NPWT included bone and/or tendon exposed deep wounds that are not suitable for early grafting or flap applications owing to the lack of supporting tissue in 27 (69.2%) patients, graft fixation in 8 (20.5%) patients, and secondary grafting following graft loss in 4 (10.3%) patients. The general success rate of NPWT was 90.7% according to indications and treatment objectives in our study.

CONCLUSION: In the light of our results, NPWT may contribute to the present conventional treatments used in severe electrical burns.

Keywords: Burn; electrical injury; NPWT.

INTRODUCTION Since the commencement of electricity in 1849, it has been one of the most potentially hazardous causes of burn injuries.

Approximately 1% of accidental deaths are caused by an electric injury. Annually, more than 1,000 deaths are reported in the United States due to electric injury, with a mortality rate of 3%–5%.[1,2] Young adult males who were injured in industrial accidents constituted a majority of high-voltage burn patients.[3] Burn wounds are different in many ways from other wounds, and their treatment is generally more challenging. In particu-

lar, deep wounds lead to serious problems both in the acute and healing periods. Despite all improved modern treatment methods, burns continue to constitute a serious problem in terms of morbidity as well as mortality. The care of burn wounds and their sequelae necessitate a different kind of expertise.[4] The pathophysiology of electrical injury has been well defined. The tissue damage is commonly severe and progressive owing to vascular injury and prolonged production of thromboxane induced by the electrical current. It is true that high temperature may be produced by the passage of electric current through the tissues, but the nature of electrical

Cite this article as: Eyvaz K, Kement M, Balin S, Acar H, Kündeş F, Karaoz A, et al. Clinical evaluation of negative-pressure wound therapy in the management of electrical burns. Ulus Travma Acil Cerrahi Derg 2018;24:456-461.

Address for correspondence: Metin Kement, M.D. Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, İstanbul, Turkey Tel: +90 216 - 458 30 00 E-mail: mkement@yahoo.com Ulus Travma Acil Cerrahi Derg 2018;24(5):456-461 DOI: 10.5505/tjtes.2018.80439 Submitted: 20.05.2017 Accepted: 16.01.2018 Online: 13.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

456

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Eyvaz et al. Clinical evaluation of negative-pressure wound therapy in the management of electrical burns

injury diverges from other thermal injuries because of some specific influences, which are at least partly responsible for the damage. The skin wound of an electrical injury is visibly circumscribed to the area of contact, and this part of the skin is dead. Deep into the skin, the zone of injury extends toward the other point of contact, thereby damaging the deeper tissues. Main vessels procedure good conduction because of their fluid content, consequently resulting in the thrombosis of digital or other main vessels.[5] Local edema that is formed depending on tissue injuries in the electrical burns, significant edema that is initiated by several factors including vasodilation, and increased microvascular permeability extravascular osmotic activity often accompany inflammation. Excessive or prolonged edema and inflammation exacerbate pain and impair wound healing. The clinical challenge becomes management, applying therapeutic intervention only when inflammation and edema worsen.[6] Negative-pressure wound therapy (NPWT) is a non-invasive method wherein controlled, negative pressure is applied on the wound to remove fluid, exudates, and infectious materials, which may promote wound healing and closure. NPWT is an alternative treatment option that has become increasingly widespread in acute and chronic wound treatment. NPWT has been recently performed on burn wounds.[7–9] In the present study, we aimed to evaluate the clinical efficacy and safety of NPWT in the treatment of the patients with electrical burns.

MATERIALS AND METHODS Design This study was retrospectively performed using a database maintained prospectively in the burn center of our hospital. All consecutive patients with electrical burns who were treated with NPWT in our center between August 2008 and December 2012 were included. Moreover, the patients who died during treatment or somehow could not complete their NPWT because of various reasons were excluded from the study.

Indications of NPWT NPWT is performed with three basic indications in our burn unit as follows: a. To decrease the bacterial load and to accelerate the formation of matrix proteins and granulation tissue in the burns that are not suitable for early grafting or flap applications owing to the lack of a supporting tissue (for example, burns with exposed bone and tendons) b. To enable graft fixation in areas where graft fixation is difficult c. To accelerate re-granulation in patients with graft loss following primary grafting. The timing and duration of the application depends on the indication.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

NPWT System Vacuum-assisted closure system (V.A.C.) ATS Therapy System [Kinetic Concept Inc (KCI), USA] was used as NPWT in our clinic during the study. The system comprises polyurethane and polyvinyl sponges to fill the tissue defects, adhesive semipermeable covers to cover the wound, an apparatus that regulates pressure and provides the connection between the wound and the device (therapeutic regulated accurate care pad), a collection cup, and a device to create negative pressure.

Parameters The following data were analyzed in our study: the demographic characteristics of the patients, accompanying comorbidities and The American Society of Anesthesiologists (ASA) scores of the patients, places of the event (house, workplace, or street), type of the electric current (high, low voltage, or arc), localizations and depths (degree) of the burns, percentage of total burned body surface area (TBSA), amputation requirement and their localizations, indications for NPWT, number of NPWT dressing changes, duration of the application, complications encountered during the application, hospitalization time, and outcomes of the therapy.

Evaluation of Outcomes The treatment results in our study were grouped as successful or unsuccessful by considering the treatment objectives in accordance with therapy indications. The objectives according to indications can be listed as follows: a. Ensuring that the wound becomes suitable for grafting or flap application for deep burns that were not previously suitable for grafting or flap application b. Minimal (<10% of area) or no graft loss in cases where graft fixation is required c. Ensuring that the wound is suitable for re-grafting in patients who had graft loss following graft application.

RESULTS During the study period, 305 patients with electrical burns were treated at our burn center; of them, NPWT was applied to 43 patients (14%). Four of them were excluded because of mortality before completion of the treatment course. Finally, 39 patients were analyzed in our study; of them, 36 were men (92.3%). The average age was 34.9±9.8 years (range, 17–63 years). The ASA scores and the accompanying morbidities are presented in Table 1.

The majority of the patients in our study (92.3%) were exposed to high voltage current. The mean TBSA was 19.3±9.8 (range, 4–44). TBSAs were ≥30% in 6 patients (15.4%); 31 patients (79.5%) had third-degree burns, while 8 of them (20.5%) had fourth-degree burns. The characteristics of the burns are presented in Table 2.

457

Eyvaz et al. Clinical evaluation of negative-pressure wound therapy in the management of electrical burns

Table 1. Demographic characteristics and accompanying

comorbidities of the patients

n

%

36

34.9±9.8

92.3

Comorbidities

Diabetes mellitus

Hypertension

2

5.1

2

5.1

Indication

n %

Burn with deep tissue

27

69.2

Lower extremity

17

43.5

Mean±SD

Age (years) Gender (male)

Table 3. Indications for negative-pressure wound therapy

ASA scores

Upper extremity

9

23

Other (gluteal region)

1

2.7

For graft fixation

8

20.5

Lower extremity

4

10

Upper extremity

3

7.6

Other (gluteal region)

1

2.7

ASA I

0

0

ASA II

30

76.9

Secondary grafting following graft loss

4

10.3

ASA III

6

15.4

Lower extremity

2

5.3

ASA IV

3

7.7

Upper extremity

1

2.7

Other (left inguinal region)

1

2.7

SD: Standard deviation.

Table 2. Location and characteristics of wounds Parameters

n %

Voltage

Table 4. Numbers and duration of negative-pressure wound therapy dressings Indication Number of Application

dressings±SD duration±SD

(days)

High

36

92.3

Low

3

7.7

Lower extremity

4.2±1.4

12.2±5.2

House

3

7.7

Upper extremity

3.6±1.1

10.7±4.7

Workplace

33

84.6

Other (gluteal region)

3±1.3

8±2.1

Street

3

7.7

For graft fixation

<15%

11

28.2

15%–30%

22

56.4

>30%

6

15.4

Secondary grafting following

19.3

graft loss

Place of occurrence

Burn percentage

Burn with deep tissue

Mean total burned body surface area (%) Burn degree

Lower extremity

3.5±1.7

8.7±4.1

Upper extremity

4±1.9

12.6±2.1

Other (gluteal region)

3±1.2

9±2.4

Lower extremity

5±2.7

16±2.5

1–2°

0

0

Upper extremity

6.1±3.1

16.3±2.4

3°

31

79.5

Other (left inguinal region)

4.2±1.8

14.5±3.4

4°

8

20.5

In our study, indications of NPWT included bone and/or tendon exposed deep wounds where granulation could not be achieved using standard dressings in 27 (69.2%) patients, graft fixation in 8 (20.5%) patients, and acceleration of re-granulation following graft loss in 4 (10.3%) patients. These indications are shown in Table 3. The numbers of dressings changed and the duration of application in accordance with indications and localizations are presented in Table 4.

The results according to indications and treatment objectives are shown in Table 5. The general success rate of NPWT was 90.7% in our study. The photographs of a patient taken during their treatment periods are shown in Figure 1a-d.

458

SD: Standard deviation.

DISCUSSION Burn management has evolved over several decades through preclinical and clinical research. NPWT was defined by Fleischmann in the 1990s and has become popular. This method, which was initially used in treating the lower extremity fasciotomies, became widespread in terms of indication in time and is being used to treat all types of acute or chronic wounds.

[7] The physiological effects of NPWT have been shown in various animal studies.[8,9] Sub atmospheric pressure applied to wounds reportedly increases blood flow, reduces edema, cleans the wound surface, decreases the bacterial load, and accelerates the formation of matrix proteins and granulation Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Eyvaz et al. Clinical evaluation of negative-pressure wound therapy in the management of electrical burns

Table 5. Success rates following negative-pressure wound therapy according to indications Indication

n %

Burn with deep tissues (n=27) Successful

24

89

Unsuccessful

3

11

Successful

7

88

Unsuccessful

1

12

Successful

4

100

Unsuccessful

0

0

For graft fixation (n=8)

Secondary grafting following graft loss (n=4)

tissue. Besides contributing to the healing of open wounds, NPWT reduces the seroma or hematoma under the graft as well as lowers the separation force between the graft and graft bed, thereby increasing the chance of graft success.[10] Although there is no high-level evidence in literature regarding NPWT in burn wounds, sub-atmospheric pressure is theoretically known to reduce edema that occurs particularly in the stasis zone and increases blood flow in the burn wounds.

Therefore, the extending and deepening of the damage may be prevented. Moreover, sub-atmospheric pressure may accelerate the healing of wounds in burn injuries through the aforementioned effects. Since the beginning of the millennium, there are several studies reporting the usage of NPWT on burn wounds. However, most of these publications are case series including few patients. To our knowledge, the only prospective randomized study in this issue is the study presented by Molnar et al.,[11] in the II. Wound Healing Association Congress, 2004. In this study, 23 patients who had (a)

(b)

burn wounds on both hands were evaluated. A dressing was applied using silver sulphadiazine on one hand of the patients, while the other hand was treated with 125 mmHg pressure NPWT. The outcomes measured in the study using Sigma Scan (Systat Software Inc, California, USA) were listed as the level of healing, the volume of the hand, hand usage abilities, grasping, and squeezing forces. In all the parameters, better results were obtained on the hands that were treated with NPWT. The final and definite results of this study have not been published yet. Similarly, Kamolz et al.[12] reported 7 patients in whom the more intense injured hand was treated with controlled applied sub atmospheric pressure the other and less injured hand was conservatively treated using a silver sulphadiazine cream. They observed a massive hyperperfusion in the NPWT treated hand, which could be a reason for the prevention of burn progression. Moreover, they reported a noteworthy amount of fluid removal and a clinically obvious edema reduction compared to the contralateral side. Additionally, Schrank et al.[13] reported some beneficial effects of NPWT in the treatment of hand burns of 11 cases.

The first study about NPWT excepting hand burns was reported by Nugent et al.,[14] who successfully used NPWT on three patients having lower extremity burns with bone exposure. In our opinion, the most interesting publication regarding this method is the study reported by Si Jack Chong et al.,[15] in which NPWT was applied like a “sandwich” according to the authors, such that it coated the bodies of three intensive care patients with extensive burns. This therapy was named as “total body dressing” by the authors. The results were reported to be positive in all patients. Another noteworthy study regarding NPWT in burn wounds is the NPWT following flap application, which was reported by Weinand et al.[16] They applied NPWT following superficial inferior epigastric flap application to a patient having third degree hand and finger burns.

In a recent Cochrane Review, Dumville et al.[17] summarized (c)

(d)

Figure 1. (a-d) Negative-pressure wound therapy (NPWT) treatment course of a patient with fourth degree electrical burn in right arm and hand. (a) Wound at the time of first arrival. (b) NPWT. (c) Post-NPWT tissue granulation. (d) Grafting of wound following NPWT.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

459

Eyvaz et al. Clinical evaluation of negative-pressure wound therapy in the management of electrical burns

the best available evidence relating to the safety and effectiveness of NPWT in adults with partial-thickness burns. They concluded that their systematic review highlighted the need for good quality research regarding the safety and effectiveness of NPWT in partial thickness burns.

To the best of our knowledge, there is almost no report regarding NPWT for electrical burns. The only publication in this subject is a case presentation reported by Gümüş et al.,[18] wherein NPWT was to treat the deep wound on the scalp following an electric shock. Therefore, our study is the most extensive publication on this subject. As a control group was not presented, the treatment results in our study were grouped as successful and unsuccessful by taking into account the treatment objectives according to indications.

These objectives were attained in more than 90% of patients in our study.

Our study had important limitations: it was a retrospective study and there was no control group. Although these limitations pose an obstacle to provide high-level evidence, the clinical outcomes of the NPWT in electrical burns were assessed as successful by our burn center clinicians, who are highly experienced in burn therapies.

Conclusions In the light of our results, NPWT may contribute to the present conventional treatments used in severe electrical burns. Nevertheless, our results should be supported by further prospective randomized studies.

Research Involving Human Participants and/or Animals The study was approved by the Institutional Research Ethics Committee. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent Informed consent was obtained from all participants or their primary relatives of deceased patients.

Conflict of interest: None declared.

2. Spies C, Trohman RG. Narrative review: Electrocution and life-threatening electrical injuries. Ann Intern Med 2006;145:531–7.

3. Kurt A, Yıldırım K, Yağmur Ç, Kelahmetoğlu O, Aslan O, Gümüş M, et al. Electrical burns: Highlights from a 5-year retrospective analysis. Ulus Travma Acil Cerrahi Derg 2016;22:278–82.

4. Tiwari VK. Burn wound: How it differs from other wounds? Indian J Plast Surg 2012;45:364–73.

5. Gajbhiye AS, Meshram MM, Gajaralwar RS, Kathod AP. The management of electrical burn. Indian J Surg 2013;75:278–83.

6. Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, et al. Burn wound healing and treatment: review and advancements. Crit Care 2015;19:243.

7. Fleischmann W, Lang E, Kinzl L. Vacuum assisted wound closure after dermatofasciotomy of the lower extremity [Article in German]. Unfallchirurg 1996;99:283–7.

8. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuumassisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg 1997;38:553–62.

9. Moiemen NS, Yarrow J, Kamel D, Kearns D, Mendonca D. Topical negative pressure therapy: does it accelerate neovascularisation within the dermal regeneration template, Integra? A prospective histological in vivo study. Burns 2010;36:764–8.

10. Thorne CH. Techniques and principles in plastic surgery. In: Thorne CH, Beasley MW, Aston SJ, Bartlett SP, editors. Grabb and Smith’s plastic surgery. 6th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2007. p. 8.

11. Molnar JA, Heimbach DM, Tredget EE, Hickerson WL, Still JM, Luterman A, et al. Prospective Randomized Controlled Multicenter Trial Applying Subatmospheric Pressure to Acute Hand Burns: An Interim Report. 2nd World Union of Wound Healing Societies’ Meeting, Paris France Jun 19–23, 2004.

12. Kamolz LP, Andel H, Haslik W, Winter W, Meissl G, Frey M. Use of subatmospheric pressure therapy to prevent burn wound progression in human: first experiences. Burns 2004;30:253–8.

13. Schrank C, Mayr M, Overesch M, Molnar J, Henkel V Donnersmarck G, Mühlbauer W, et al. Results of vacuum therapy (v.a.C.) of superficial and deep dermal burns [Article in German]. Zentralbl Chir 2004;129:59– 61.

14. Nugent N, Lannon D, O’Donnell M. Vacuum-assisted closure - a management option for the burns patient with exposed bone. Burns 2005:31;390–3.

15. Chong SJ, Liang WH, Tan BK. Use of multiple VAC devices in the management of extensive burns: the total body wrap concept. Burns 2010;36:e127–9.

16. Weinand C. The Vacuum-Assisted Closure (VAC) device for hastened attachment of a superficial inferior-epigastric flap to third-degree burns on hand and fingers. J Burn Care Res 2009;30:362–5.

REFERENCES

17. Dumville JC, Munson C, Christie J. Negative pressure wound therapy for partial-thickness burns. Cochrane Database Syst Rev 2014;15:CD006215.

1. Lee RC. Injury by electrical forces: pathophysiology, manifestations, and therapy. Curr Probl Surg 1997;34:677–764.

18. Gümüş N. Negative Pressure Dressing for the Treatment of High-Voltage Electrical Burn Injury. J Burn Care Res 2010;31:215.

460

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Eyvaz et al. Clinical evaluation of negative-pressure wound therapy in the management of electrical burns

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Negatif başınçlı yara tedavisinin elektrik yanıklarında klinik olarak değerlendirilmesi Dr. Kemal Eyvaz, Dr. Metin Kement, Dr. Salim Balin, Dr. Hakan Acar, Dr. Fikri Kündeş, Dr. Alev Karaoz, Dr. Osman Civil, Dr. Mehmet Eser, Dr. Levent Kaptanoglu, Dr. Selahattin Vural, Dr. Nejdet Bildik Sağlık Bilimleri Üniversitesi, Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği Yanık Ünitesi, İstanbul

AMAÇ: Bu çalışmada, elektrik yanıklarında kullandığımız negatif basınçlı yara tedavisinin (NBYT) klinik etkinliğini ve güvenilirliğini değerlendirmeyi amaçladık.

GEREÇ VE YÖNTEM: Çalışma, hastanemizin yanık merkezinde ileriye yönelik olarak tutulan veri tabanı kullanılarak geriye dönük olarak yapıldı.

Ağustos 2008 ile Aralık 2012 tarihleri arasında merkezimizde NBYT uygulanan elektrik yanıklı hastalar ardışık olarak çalışmaya dahil edildi. Çalışmamızdaki tedavi sonuçları, tedavi endikasyonları ve hedefleri dikkate alınarak başarılı veya başarısız olarak değerlendirildi.

BULGULAR: Çalışmamızda toplam 39 hasta analiz edildi. Otuz altısı erkekti (%92.3). Ortalama yaş 34.9±9.8 (dağılım 17–63) idi. Çalışmamızdaki hastaların çoğunluğu (%92.3) yüksek voltaja maruz kalmıştı. Ortalama TBSA 19.3±9.8 (dağılım 4–44) idi, altı hastada (%15.4) TBSA %30’un üzerindeydi. Otuz bir hastada (%79.5) 3. derece yanık, sekiz hastada (% 20.5) 4. derece yanık vardı. Çalışmamızda, NBYT endikasyonları; 27 hastada (%69.2) granülasyonun standart pansumanlar ile elde edilemeyeceği kemik ve/veya tendon içeren erken greftleme ve flap uygulamaları için yeterli destek dokusu olmayan derin yaralanmalar, sekiz hastada (%20.5) greft fiksasyonu, dört hastada (%10.3) ise primer greft kaybını takiben sekonder grefti desteklemek şeklindeydi. Çalışmamızda NBYT’nin endikasyon ve tedavi hedeflerine göre genel başarı oranı %90.7 olarak tespit edildi.

TARTIŞMA: Sonuçlarımız, NBYT uygulamasının ciddi elektrik yanıklarında kullanılan geleneksel konvansiyonel tedavilere katkıda bulunabileceğini göstermektedir.

Anahtar sözcükler: Elektrik yanığı, negatif basınçlı yara tedavisi; yanık.

Ulus Travma Acil Cerrahi Derg 2018;24(5):456-461

doi: 10.5505/tjtes.2018.80439

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

461

ORIG I N A L A R T IC L E

Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations Emin Sir, M.D.,1

Alper Aksoy, M.D.,2

Meliha Kasapoğlu Aksoy, M.D.3

1

Department of Plastic, Reconstructive and Aesthetic Surgery, Private Practice, İzmir-Turkey

2

Department of Plastic, Reconstructive and Aesthetic Surgery, Acıbadem Konur Surgical Center, Bursa-Turkey

3

Department of Physical Medicine and Rehabilitation, University of Health Sciences, Bursa Yüksek İhtisas Training and

Research Hospital, Bursa-Turkey

ABSTRACT BACKGROUND: Replantation is the gold standard procedure for traumatic amputation of fingertips. Reposition flap procedure is performed using nail-bone complex as a free graft and covering graft site with a flap to preserve original finger length, nail complex, and sensory functions of fingertip in pateints where microsurgical methods cannot be applied. In our study, we aimed to compare the long-term outcomes of patients with amputated fingertips who underwent replantation or reposition flap procedures.

METHODS: Thirty-five patients of replantation and 28 patients of reposition flap procedures only for 2nd, 3rd, and 4th fingertip amputations were included in the study. Complete fingertip amputations involved Foucher zones 2 and 3. The patients were followed up postoperatively for a median period of 13 months (9–23 months). All patients were assessed with static and dynamic 2-point discrimination tests, Semmes–Weinstein monofilament test, and cold intolerance test for the development of neuroma on the donor site.

RESULTS: In 5 patients, replantation procedure failed. In such failed patients, after the removal of necrotic tissues, the stump was either repaired or reconstruction with a flap was applied. Wound dehiscence was observed at the lateral sides of the flaps in 2 patients who underwent reposition procedures.

CONCLUSION: Reposition flap repair can be a good cost-effective alternative to other fingertip repair procedures in appropriately selected patients who are not amenable to microsurgery. It preserves the length and sensory functions of fingertips and enables patients to return to their daily life as soon as possible.

Keywords: Fingertip amputation; replantation; reposition flap; trauma.

INTRODUCTION Traumatic fingertip amputation is the most common injury of the upper extremities. Treatment for fingertip amputation may vary from a simple debridment or secondary healing to replantation, which is a complicated procedure. No matter what type of surgical method is performed, the main goal is to have a fingertip that functions normally and is aesthetically acceptable.[1] Recently, replantation has been considered as a gold standard.[2] It improves the reconstruction of the missing part by using its original tissue. Minimizing donor site mor-

bidity is another advantage of replantation. Replantation is technically difficult in amputations involved with distal to distal interphalangeal joint because of the small diameter of an artery and venous problems. Replantation may not be always applicable as it requires microsurgical experience and special surgical instruments. In addition, it is a costly and challenging operation. Improper replantation treatment could result in deformity, such as shortened fingertip, neuroma of the finger pulp, loss of nail complexity, and non-aesthetic appearance.[3]

Cite this article as: Sir E, Aksoy A, Kasapoğlu Aksoy M. Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations. Ulus Travma Acil Cerrahi Derg 2018;24:462-467.

Address for correspondence: Emin Sir, M.D. Mimar Sinan Mahallesi, Ali Çetinkaya Bulvarı, No: 69, K: 3, D: 6, Alsancak, 35220 İzmir, Turkey Tel: +90 532 - 589 85 51 E-mail: eminsir@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):462-467 DOI: 10.5505/tjtes.2018.67217 Submitted: 20.05.2017 Accepted: 04.01.2018 Online: 10.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

462

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Sir et al. Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations

Reposition flap procedure is performed by using nail-bone complex as a free graft and covering graft site with a flap to preserve the original finger length, nail complex, and sensory functions of fingertip in patients where microsurgical methods cannot be applied.[4] This method has been indicated to cause clubbed nails, ungual dystrophy, joint stiffness, and unsatisfactory finger length.[5] Therefore, in our study, we aimed to compare the long-term results of the patients with amputated fingertips who underwent replantation or reposition flap procedures.

MATERIALS AND METHODS Study Design Between May 2010 and January 2013, 35 patients of replantation and 28 patients of reposition flap procedures only for 2nd, 3rd, and 4th fingertip amputations were included in the study. Replantations were performed for patients with guillotine amputations (n=17), crush injuries (n=12) and avulsions (n=7). Reposition flap procedures were applied for patients with avulsion (n=19) and crush type injuries (n=9). Majority of the amputations were caused by accidents encountered at workplaces. Complete fingertip amputations involved Foucher zones 2 and 3. Average ischemia time was 3.5 (range, 1–9) hours. All patients were operated under axillary block anesthesia.

Bone stabilization was achieved using Kirschner wire without damaging the interphalangeal joint. Under microscopic visualization, central artery (n=29) and lateral digital artery anastomoses (n=6) were performed. In 4 patients who were not amenable for end-to-end anastomosis, vein grafts were used.

Palmar vein anastomoses were performed in 25 patients. All anastomoses were performed using 10/0 or 11/0 nylon sutures. Nerve coaptation was performed in 23 patients. Average operative time was 90 (range, 80–120) minutes. The patients received 1 cc 5000 IU heparin during operation and 100 mg acetylsalicylic acid for 30 days. Since vein repair was performed during replantation, no bleeding episode was encountered that obviated the need for blood transfusion. The patients were discharged after an average of 3 (range, 2–8) days.

(b)

Proximal segment was partially debrided before the application of the reposition flap. Skin of the distal segment was harvested as full-thickness skin graft; after removing all of the remaining soft tissues from operative site, a monocortical bone segment was constructed, and by using a 0.8 mm Kirschner wire bone-nail complex, it was fixed to the proximal segment.

Nail beds were repaired with 6/0 rapid vicryl sutures. In all patients, reverse homodigital flaps were harvested from the non-dominant site to cover the naked bone. After dissection of the artery and nerve, the proximal segment of the artery was ligated and the proximal end of the nerve was embedded in soft tissue. Following elevation of the flap, the nerve of the flap was coapted to the other digital nerve of the finger with an incision made on the appropriate site distal to the digital nerve, which was closed with 10/0 nylon sutures. Flap was sutured on the bone with 6/0 prolene sutures. If it was applicable, then the flap donor sites were primarily closed. The skin of the amputed segment was used to prepare a full-thickness skin graft for donor site wounds, which were not suitable for primary closure (Fig. 1). Average operative time was 60 (range, 50–90) minutes. Kirschner wires were removed after an average of 31.2 (range, 24–35) days, and the patients were then included in the rehabilitation program. The patients received an average of 29.4 (range, 28–33) sessions of rehabilitation.

RESULTS

Surgical Technique For Replantations

(a)

Surgical Technique For Reposition Flap

(c)

In all patients, sensory functions, appearance, lengths of the fingers, nail structure, and new finger pulp were evaluated by the same person. The patients’ period off work during the process was approximately 80.6 (range, 78–93) days in the replantation and 82.3 (range, 80–95) days in the flap reposition series. The patients were followed up for an average of 13 (range, 9–23) months.

In 5 patients, replantation procedures failed. In these failed patients, after the removal of necrotic tissues, the stump was either repaired or reconstruction with a flap was applied. The lengths of replanted fingers were approximately 2.3 (range, 0–10) mm shorter than the corresponding finger of the contralateral hand. As for nail deformities, 1 patient

(d)

Figure 1. (a, b) Amputated part was prepared and fixed using Kirschner wire. (c) Flap was elevated. (d) Flap was sutured and donor area was closed using the skin of the amputated part.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

463

Sir et al. Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations

Table 1. Comparison for replantation and reposition flap groups

Replantation group (n=35)

Reposition flap group (n=28)

Age (years) [mean (range)]

38.2 (18–52)

39.8 (18–57)

Gender (female/male)

7/28

6/22

Hand (right/left)

20/15

18/10

Foucher (zone 2/zone 3)

8/27

10/18

Table 2. The comparison of the group’s results

Replantation group (n=35)

Reposition flap group (n=28)

4.5 (2–7)

5.8 (2–9)

4.1

4.7

Weber static test (mm) [mean (range)] Weber dynamic test (mm) (mean) 2-point discrimination test (mm) [mean (range)]

3.10 (1.65–4.09)

3.42 (1.68–4.13)

Self-satisfaction (1-10)

8.5

7.1

Cold intolerance (%)

83%

83%

Neuroma

with a hook nail and 3 patients with a minimal increase in longitudinal curvature were observed. Movements of proximal interphalangeal and distal interphalangeal joints were not restricted. Fingertip sensation was measured as 4.5 (range, 2–7) mm in Weber static test and an average of 4.5 mm in Weber dynamic test. Average value in 2-point discrimination test was 3.10 (range, 1.654.09) mm. Neuroma formation was observed in 3 patients. In 83% of the patients, varying degrees of cold intolerance were observed.

Wound dehiscence was observed at the lateral sides of the flaps in 2 patients who underwent reposition procedures. These wound dehiscences were managed with dressings for a certain period and then left to secondary healing. The length of the patients’ fingers was an average of 1.4 (range, 0–10) mm longer when compared with the corresponding finger of the other hand. Two patients had clubbed nails. Furthermore, flexion contracture of the DIP joint was detected in 6 patients. In the short-term, restriction in the movement of PIP joint was observed, whereas in the long-term, flexion contracture of the PIP joint was observed in 6 patients. These

(a)

(b)

3 1

contractures were corrected with Z-plasties. Weber static and dynamic test results were 5.8 (range, 2–9) mm and 4.7 mm, respectively. Average measurement for 2-point discrimination test was 3.42 (range, 1.68–4.13) mm. Neuroma was detected in 1 patient. In 87% of the patients, varying degrees of cold intolerance were detected.

In patients who underwent replantation or flap reposition procedures, if images of the fingers were scored between 1 and 10 points, average scores were 8.5 and 7.1 points, respectively.

Intergroup comparisons are summarized in Tables 1 and 2.

Patient Presentations Patient 1: A 36-year-old woman had a crush injury of her left index finger as a result of a work accident; the fingertip was amputated. Reposition flap was performed for the amputated finger. Flap viability was good and the length of finger was preserved at the postoperative 10th month appearances of the finger (Fig. 2).

(c)

(d)

Figure 2. (a) Crush injury of the left index finger. (b-d) Postoperative result at the 8th month.

464

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Sir et al. Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations

(a)

(b)

(c)

(d)

Figure 3. (a) Clean-cut injury of the patientâ&#x20AC;&#x2122;s right middle and ring fingers. (b) Intra-operative photograph showing palmar vein anastomoses. (c,d) Postoperative good aesthetic results at the 15th month.

Patient 2: A 37-year-old man had a clean-cut injury of his left middle and ring fingers as a result of a work accident; the fingertip was amputated. Replantation was performed to the amputated middle and ring fingers. Palmar vein anastomoses was performed and all replantations were successful.

The length of fingers was preserved at the postoperative 15th month (Fig. 3).

DISCUSSION Sophisticated microsurgery instruments and techniques enable anastomosis of smaller caliber vessels. Anastomosis of such smaller sized vessels has increased the success rate of replantation of fingertip amputations. Therefore, during fingertip amputations, if the amputated segment is in a good condition and is preserved very well during transportation, then for excellent esthetical and functional results, replantation is the gold standard intervention.[6] Though success rates of replantation range between 80% and 90%,[7â&#x20AC;&#x201C;9] depending on the amputed segment, replantation cannot be performed every time. If replantation is not performed, the patient is left to secondary healing, and this results in the patient taking a long time to return to his/her routine daily life and appearance of the fingertip may not be satisfactory in aesthetic and functional aspects.[10] As a consequence of secondary healing or use of local flaps, the affected finger shortens, and not only its grip strength decreases but also there is a decrease in motor activity while holding small objects.[11] In patients where replantation cannot be performed, Mantero described flap reposition procedure in 1975 to avoid the shortening of the affected finger.[12] Mantero used cross-finger flap technique with a success rate of approximately 75%. Because Manteroâ&#x20AC;&#x2122;s surgical procedure is multi-staged, Foucher et al.[5] described his single-stage procedure in 1995. They reported that the reposition flap procedure should be used especially in crush injuries with fingertip amputations where success rates are relatively low, time to return to daily life activities is prolonged, and higher operative costs are incurred by secondary interventions to get rid of the effects of failed transplantation procedures. Conversely, varying success rates have been reported for the use of reposition procedures. As a result of studies performed by Dubert et al.,[13] clubbed nails were observed in almost all patients. In our series, in all patients, non-dominant homodigital flap was used at a single session Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

and all reposition flap procedures were successful apart from 2 patients with wound site dehiscence. A significant intergroup difference was not found with respect to finger length.

During the follow-up period, 2 patients with clubbed nails were observed among patients with reposition flaps. In our replantation series, 1 patient of hook nail was detected. In our reposition series, during the short-term observation period, 3 patients had nail dystrophy and 1 patient had a short nail problem. However, these problems disappeared in the long-term. As demonstrated in cadaver studies, we believe that blood flow in nail is supplied from distal phalanx. During the procedure, fixation of distal phalanx on amputated part monocortically and overlay its bone with flap will result in improvement in healing, decrease of resorption on distal phalanx bone and prevention of nail.[14] One of the most important postoperative problems of fingertip amputations is fingertip numbness, which can be resolved with the use of volar or lateral V-Y advancement flaps. As these flaps cannot be designed for large defects and they cannot be extended beyond the distal interphalangeal joint, they have limited indications of use.[15] Reposition flap has some advantages such as excellent recovery of fingertip sensory functions with its soft tissue support, ability to cover large defects and a larger rotation arch than other local flaps.[16] In some studies, no significant difference has been reported at the end of the first postoperative year in patients who had or had not undergone Tamai type 1 distal finger replantations.[17] However, in some other studies, in patients where nerve repair is not feasible after Tamai type 1 injuries, similar outcomes have been reported after the repair of one or two terminal branches of the nerve.[2] Before repositioning the flap, as described in the literature, coaptation of the nerve of the flap graft harvested from an appropriate site distal to the other digital nerve of the finger was performed.[18] During our postoperative follow-ups, we did not find a significant difference between patients who underwent reposition flap procedures and replantation with respect to fingertip sensory recovery. Besides, two-point discrimination measurements were found to be similar to the outcomes of some studies.[18,19] Another advantage of nerve repair is to prevent neuroma formation on the nerve terminal to be exposed and then minimize any pain, which will decrease the quality of life.

465

Sir et al. Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations

When compared to other fingertip reconstructions (i.e., Thenar or cross-finger flap), reposition flap procedures can be used in medical practice in that it is a single-stage method without disadvantages of other methods, such as joint stiffness, restricted range of motion of the joint, and requirement of more than one session of surgery.[20] Potential complications may be related to the flap or composite graft. Providing a good blood supply support may eliminate complications of composite grafts. To prevent the development of restricted extension of the fingertip, postoperative long-term immobilization should be avoided and limited dissection of the distal segment should be performed.[3] However, postoperative problems related to PIP joint due to elevation of reverse homodigital flap and articulopathies of DIP joint associated with reposition of the flap can be observed. Even if the flap is dissected perfectly, because of geometric configuration of the flap, primary and secondary contractions can be observed in the long-term due to primary closure and after its repair with a graft. As a consequence, restricted flexion and extension of the fingertips can be observed. To avoid restricted flexion or extension, rehabilitation should be initiated at an early stage after healing of the flap and in patients of need, it should be prolonged. Contractures formed can be opened with Z-plasties.

In our series, we performed Z-plasties in 6 patients and they received an average of 29.4 (range, 28–33) sessions of rehabilitation.

Reposition procedure is less expensive and simple without requiring any special surgical equipment. Microsurgical methods are relatively more costly and require long-term immobilization.[21]

Conclusion Despite its technical challenges, reposition flap repair can be a good cost-effective alternative to other fingertip repair methods in appropriately selected patients who are not amenable to microsurgery. It preserves the length and sensory functions of fingertips and enables patients to return to their daily life as soon as possible.

Conflict of interest: None declared.

REFERENCES 1. Allen MJ. Conservative management of finger tip injuries in adults. Hand 1980;12:257–65.

2. Yamano Y. Replantation of the amputated distal part of the fingers. J Hand Surg Am 1985;10:211–8

466

3. Braga-Silva J, Jaeger M. Repositioning and flap placement in fingertip injuries. Ann Plast Surg 2001;47:60–3.

4. Robert N, Chassat R, Couturier C, Delpit X, Masmejean E. “Repositionflap”: A Therapeutic alternative in fingertips amputations. Ann Chir Plast Esthet 2015;60:299–304.

5. Foucher G, Norris RW. Distal and very distal digital replantations. Br J Plast Surg 1992;45:199–203.

6. Hattori Y, Doi K, Ikeda K, Estrella EP. A retrospective study of functional outcomes after successful replantation versus amputation closure for single fingertip amputations. J Hand Surg Am 2006;31:811–8.

7. Bora A, Ada S, Ozerkan F, Tetik F. Replantations and their functional results: The Turkish experience. Microsurgery 1993;14:97–101.

8. Cheng GL, Pan DD, Qu ZY, Lin B, Yang ZX, Fang GR, et al. Digital replantation. A ten-year retrospective study. Chin Med J (Engl) 1991;104:96–102.

9. Glas K, Biemer E, Duspiva KP, Werber K, Stock W, Herndl E. Longterm follow-up results of 97 finger replantations. Arch Orthop Trauma Surg 1982;100:95–8.

10. Elliot D, Sood MK, Flemming AFS, Swain B. A comparison of replantation and terminalization after distal finger amputation. J Hand Surg [Br] 1997;4:523–9.

11. Söderberg T, Nyström A, Hallmans G, Hultén J. Treatment of fingertip amputations with bone exposure. A comparative study between surgical and conservative treatment methods. Scand J Plast Reconstr Surg 1983;17:147–52.

12. Mantero R, Bertolotti P. Reimplantation of the finger tips using a crossfinger technique [Article in French]. Ann Chir 1975;29:1019–23.

13. Dubert T, Houimli S, Valenti P, Dinh A. Very distal finger amputations: replantation or “reposition-flap” repair? J Hand Surg Br 1997;22:353–8.

14. Kumar VP, Satku K. Treatment and prevention of “hook nail” deformity with anatomic correlation. J Hand Surg Am 1993;18:617–20.

15. Ozaksar K, Toros T, Sügün TS, Bal E, Ademoğlu Y, Kaplan I. Reconstruction of finger pulp defects using homodigital dorsal middle phalangeal neurovascular advancement flap. J Hand Surg Eur 2010;35:125– 9.

16. Chen C, Tang P, Zhang X. Sensory reconstruction of a finger pulp defect using a dorsal homodigital island flap. Plast Reconstr Surg 2012;130:1077–86.

17. Hirase Y. Salvage of fingertip amputated at nail level: new surgical principles and treatments. Ann Plast Surg 1997;38:151–7.

18. Yazar M, Aydın A, Kurt Yazar S, Başaran K, Güven E. Sensory recovery of the reverse homodigital island flap in fingertip reconstruction: a review of 66 cases. Acta Orthop Traumatol Turc 2010;44:345–51.

19. Karamese M, Akatekin A, Abac M, Koplay TG, Tosun Z. Fingertip Reconstruction with reverse adipofascial homodigital flap. Ann Plast Surg 2015;75:158–62 20. Vuppalapati G, Oberlin C, Balakrishnan G. “Distally based dorsal hand flaps”: clinical experience, cadaveric studies and an update. Br J Plast Surg 2004;57:653–67.

21. Netscher DT, Meade RA. Reconstruction of fingertip amputations with full-thickness perionychial grafts from the retained part and local flaps.

Plast Reconstr Surg 1999;104:1705–12.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Sir et al. Comparisons between long-term outcomes of the use of reposition flaps and replantations in fingertip amputations

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Parmak ucu amputasyonlarında repoziyon flebi kullanımı ve replantasyonların uzun dönem sonuçlarının karşılaştırılması Dr. Emin Sir,1 Dr. Alper Aksoy,2 Dr. Meliha Kasapoglu Aksoy3 Serbest Hekim, Plastik, Rekonstüktif ve Estetik Cerrahi Bölümü, İzmir Acıbadem Konur Cerrahi Merkezi, Plastik, Rekonstüktif ve Estetik Cerrahi Bölümü, Bursa 3 Sağlık Bilimleri Üniversitesi Bursa Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Fiziksel Tıp ve Rehabilitasyon Kliniği, Bursa 1 2

AMAÇ: Parmak ucu amputasyonlarında replantasyon altın standarttır. Repozisyon flebi, replantasyonun uygulanamadığı durumlarda parmak uzunluğunu, tırnak kompleksini ve parmak ucu duyusunu korumak amacıyla yapılan, tırnak-kemik kompleksinin serbest greft olarak kullanılması ve flep ile örtülmesi esasına dayanan bir yöntemdir. Bu çalışmada parmak ucu amputasyonlarında yapılan replantasyonlar ile repozisyon flebi uygulanan hastalarının uzun dönem sonuçlarının değerlendirilmesini karşılaştırılması amaçlanmıştır.

GEREÇ VE YÖNTEM: Çalışmaya 2., 3. ve 4. parmakta Foucher sınıflamasına göre zone 2 ve zone 3 parmak ucu ampütasyonu nedeniyle başvuran ve replantasyon yapılmış 35 hasta, repozisyon flebi uygulanmış 28 hasta dahil edildi. Bütün hastalar ortalama 13 ay (9–23 ay) takip edildi. Bütün hastalar statik ve dinamik iki nokta testi, Semmes-Weinstein monofilaman testi, soğuk intoleransı ve verici saha nöroma gelişimi açısından değerlendirildi.

BULGULAR: Replantasyon yapılan beş hastada işlem başarısız oldu. Bu hastaların hepsinde nekrotik dokular uzaklaştırıldıktan sonra lokal flep ile onarım yapıldı. Repozisyon flebi uygulanan iki hastanın flep kenarlarında ayrılma oldu ve pansuman ile takip sonrası sekonder iyileşme gözlendi.

TARTIŞMA: Repozisyon flebi mikrocerrahi uygulanamayan durumlarda ve uygun seçilmiş hastalarda, parmak ucu uzunluğunu ve duyusunu koruyan, hastanın gündelik yaşamına bir an önce dönmesini sağlayan bir yöntemdir ve parmak ucu onarımlarında diğer yöntemlere iyi bir alternatif olabilir.

Anahtar sözcükler: Amputasyon; parmak ucu; replantasyon; repozisyon flebi.

Ulus Travma Acil Cerrahi Derg 2018;24(5):462-467

doi: 10.5505/tjtes.2018.67217

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

467

ORIG I N A L A R T IC L E

Does computerized tomography help to shorten the immobilization period in the plaster treatment of nondisplaced scaphoid fractures?

Hüseyin Çümen, M.D.,1

Altuğ Duramaz, M.D.,2

Cemal Kural, M.D.2

1

Department of Orthopedics and Traumatology, Hakkari State Hospital, Hakkari-Turkey

2

Department of Orthopedics and Traumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: There are conflicting results regarding the duration of the plaster treatment of nondisplaced scaphoid fractures.

The aim of the present study was to evaluate the healing process and to determine the role of computed tomography (CT) on shortening the duration of plaster treatment of nondisplaced scaphoid fractures.

METHODS: A total of 42 patients diagnosed with nondisplaced scaphoid fractures between January 2012 and January 2014 were investigated. Fractures were classified according to anatomical locations and displacement degree. Fractures were short-arm plastered enclosing thumb after non-displacement was confirmed by CT. Radiological evaluation was performed using two-planned radiographs at 2-week intervals. Patients were divided into two groups as union and non-union according to their bone healing in the CT scan at week 4 of the fracture. The cast was removed in the union group.

RESULTS: Regarding anatomical location, 8 patients were classified as distal, 30 were waist region, and 4 were proximal fractures.

Among 42 patients with a mean age of 31.95±13.11 years, the union was determined in 41 patients, and the plasters were removed at the end of 4 weeks. Patients were divided into two groups, non-union and union, in terms of fracture healing at the end of 4 weeks.

There were highly statistically significant differences between the groups regarding translation degree, contact surface rates, and displacement status (p=0.001, p=0.001, and p=0.001, respectively).

CONCLUSION: It has been shown that determination of high union rates in CT accomplishes the non-requirement of long-term plaster treatment in patients with nondisplaced scaphoid fractures after follow-up with plasters.

Keywords: Computed tomography; fracture healing; scaphoid fractures; short-term plaster treatment.

INTRODUCTION Scaphoid fractures are the most common fractures among the carpal bone (60%–70%) with a mean incidence reported as 23–43/100,000.[1] Scaphoid fractures are frequently diagnosed late or misdiagnosed since the scaphoid fracture line may not be defined clearly in standard radiographs. For that reason, early healing period problems negatively affect the prognosis. Scaphoid fractures are eligible for complications, such as non-union, malunion, humpback deformity, avascular necrosis (AVN), or collapses in the carpal bones. The non-union rate

is reported as 4%–10% in properly immobilized nondisplaced fractures.[2] High healing rates are obtained with early diagnosis and appropriate treatment. The first treatment method is the conservative treatment, plaster, in nondisplaced, stable fractures with 90% to 95% healing.[3] The duration of plaster treatment also changes according to the fracture site. Fractures of the distal pole usually heal within 6 weeks, whereas fractures involving the proximal pole may require ≥6 months of plaster immobilization.[4] There are conflicting results regarding the duration of plaster treatment in previous studies.

In the literature, short-arm plasters have been suggested to

Cite this article as: Çümen H, Duramaz A, Kural C. Does computerized tomography help to shorten the immobilization period in the plaster treatment of nondisplaced scaphoid fractures? Ulus Travma Acil Cerrahi Derg 2018;24:468-473.

Address for correspondence: Altuğ Duramaz, M.D. Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmataloji Kliniği, İstanbul, Turkey Tel: +90 212 - 414 71 71 E-mail: altug.duramaz@yahoo.com Ulus Travma Acil Cerrahi Derg 2018;24(5):468-473 DOI: 10.5505/tjtes.2018.32069 Submitted: 14.08.2017 Accepted: 16.01.2018 Online: 10.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

468

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Çümen et al. Plaster treatment of nondisplaced scaphoid fractures

perform for 8 weeks in patients with scaphoid waist fractures.[5] In addition, short-arm plasters have been advised to be kept for 12 weeks in the treatment of scaphoid fractures.

[6] In another study, it has been shown that 6 weeks of plaster treatment in nondisplaced scaphoid fractures is enough, but treatment should be performed by long-arm plasters.[7] Evaluation of union may not be visible in the follow-up with standard radiographs alone at 3 months, and thus computed tomography (CT) scans that contain a series performed in the longitudinal axis of the scaphoid are useful to ensure that the fracture is truly healed.[3] Our hypothesis was that using CT to evaluate the bone healing in scaphoid fractures would allow in many cases to quit immobilization earlier than usually suggested by most previous studies.

The aim of this retrospective study was to evaluate the healing process and to determine the role of CT on shortening the duration of plaster treatment of nondisplaced scaphoid fractures.

Figure 1. Anterior–posterior and lateral radiographs of the patients at first admission (white arrows show the fracture line).

MATERIALS AND METHODS The present study was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Institutional review board approval was obtained from the local ethics committee. Patients ≥18 years old, who were admitted to the orthopedics and traumatology emergency rooms between January 2012 and January 2014, and diagnosed with nondisplaced scaphoid fractures and treated with conservative short-arm plasters enclosing thumb were investigated. Patients ≤18 years old, who were pregnant, with a history of previous scaphoid fractures on the same side, and who did not have CT controls on follow-up were excluded from the study. A total of 42 (8 female and 34 male) patients were included in the study. The mean age of the patients was 31.95±13.11 (18–71) years. Trauma type was simple fall in 39 patients and a traffic accident in 2 patients. The cause of fracture was sports trauma in one patient who had a small cyst (2 mm). In addition, the accompanying radius distal end fracture was observed in two of the patients. Fractures were localized on the distal scaphoid in 8 patients, proximal scaphoid in 4 patients, and waist of the scaphoid in 30 patients. Standard two-planned radiographs and ulnar deviated hand–wrist anteroposterior radiographs were obtained during the first admission of patient’s radiographs to the emergency room (Fig. 1). CT (Somatom 40 detector; Siemens, Germany) sections were obtained in the axial, sagittal, and coronal planes at 1 mm intervals in order to determine the fracture of the patients with suspicious physical examination results who did not have any sign of fracture in standard radiographs (Fig. 2).

The radiographic evaluation also comprised an identification of fracture location (proximal, middle, or distal third), comminution, translation, displacement, and presence of a humpback deformity.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Figure 2. Axial, sagittal, and coronal CT images of the patients at first admission (white arrows show the fracture line).

Patients diagnosed with nondisplaced scaphoid fractures were treated using short-arm plasters enclosing thumb. All patients were controlled every 2 weeks clinically and radiologically. Patients were divided into two groups as union and non-union according to bone healing in the CT scan at week 4 of the fracture. Two-planned radiographs and CT evaluations were re-obtained from the patients for investigation of healing, and the plasters were removed in patients in the union group at the end of 4 weeks (Figs. 3 and 4). Patients were allowed passive exercises, but they were advised not to perform heavy exercises and contact sports. Patients without appropriate fracture healing at the end of 4 weeks were continued to be followed up with short-arm plaster, and they were informed about surgical treatment in the case of non-union. After collection of data, regarding the sagittal translation degrees observed during follow-up, fractures were classified as mildly displaced (<1 mm), moderately displaced (1–1.5 mm), and severely displaced (>1.5 mm) with the evaluation of CT images at the end of 4 weeks.

469

Çümen et al. Plaster treatment of nondisplaced scaphoid fractures

Table 1. Descriptive features of the patients

Age (years), Mean±SD (min-max)

n

%

31.95±13.11

(18 – 71)

Gender

Female

8

19

Male

34

81

Trauma type

Simple fall

39

92.9

Sports trauma

1

2.4

Traffic accident

2

4.8

No

40

95.2

2

4.8

8

19

Accompanying fracture Figure 3. Anterior–posterior and lateral radiographs of the patients at the end of 4 weeks (white arrows show the healing of scaphoid fracture).

Distal radius

Fracture location Distal Proximal

4

9.5

Waist

30

71.5

Minimal

37

88.1

4

9.5

1

2.4

1

2.4

Translation Moderate

Severe Union percentage at fracture line 25–49%

Figure 4. Axial, sagittal, and coronal CT images of the patients at the end of 4 weeks (white arrows show the healing of scaphoid fracture).

We classified the union percentage as 0%–24%, 25%–49%, 50%–74%, and 75%–100% based on the method described by Singh et al.[8] regarding the communication between fracture fragments. Bone union was defined as the presence of at least 50% union at the fracture line with the formation of bone bridges in all CT slices.[9] The fracture that did not accomplish at least 50% union with plaster alone was accepted as failed plaster treatment. The time to plaster removal was verified and was noticed in weeks. The patient who failed to have at least 50% union was followed up for >3 months with conservative treatment.

Statistical analysis was performed using the NCSS (Number Cruncher Statistical System) 2007 program (Kaysville, UT, USA). Mann–Whitney U test was used for comparison of quantitative data. Fisher–Freeman–Halton test was used for comparison of qualitative data. A p value <0.05 was considered as statistically significant. Some parameters were statistically significant at an advanced level. A p value <0.001 was used to demonstrate the advanced statistical significance.

470

50–74%

4

9.5

75–100%

37

88.1

Mild

37

88.1

Moderate

4

9.5

Severe

1

2.4

Displacement observed during follow-up

SD: Standard deviation; Min: Minimum; Max: Maximum.

RESULTS Translation was observed as minimal in 37 cases, whereas it was moderate in 4 patients and severe in 1 patient. Union at the fracture line was observed as between 25% and 49% in 1 patient, whereas it was between 50% and 74% in 4 patients and 75% and 100% in 37 patients. Displacement was moderate in 4 patients, severe in 1 patient, and was not observed in 37 patients (Table 1). Patients were divided into two groups, non-union and union, in terms of fracture healing at the end of 4 weeks. There was no any statistically significant difference between the groups regarding the age distributions of the patients (p=0.761; p<0.05). However, there was a highly statistically significant difference between the groups regarding translation degree (p=0.001; p<0.01). The rate of minimal translation was significantly high among patients in the union Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Çümen et al. Plaster treatment of nondisplaced scaphoid fractures

Table 2. Comparison of the groups regarding bone healing with the evaluation of CT scans at the end of 4 weeks

Union situation

p

Non-union

Union

30.14±0.01

32.31±13.74

Age (years) Mean±SD

Min-max (median)

30–31 (30.1)

18–71 (28.0)

0.761

a

Translation, n (%)

Minimal

0 (0)

37 (90.2)

Moderate

0 (0)

4 (9.8)

Severe

1 (100)

0 (0.0)

b

0.001**

b

0.001**

b

0.001**

b

0.001**

Union percentage at fracture line, n (%)

25%–49%

1 (100)

0 (0.0)

50%–74%

0 (0)

4 (9.8)

75%–100%

0 (0)

37 (90.2)

Displacement observed during follow-up, n (%)

Mild

0 (0)

37 (90.2)

Moderate

0 (0)

4 (9.8)

Severe

1 (100)

0 (0.0)

0 (0)

8 (19.5)

1 (100)

3 (7.3)

0 (0)

30 (73.2)

Fracture location, n (%)

Distal

Proximal

Waist

Mann-Whitney U test; bFisher-Freeman-Halton test; **p<0.01.

a

group (p=0.001; p<0.01). There was a highly statistically significant difference between the groups regarding the rate of union at fracture line and displacement (p=0.001 and p=0.001, respectively; p<0.01). Union at fracture line of 75%–100% was significantly high among patients with the union of fractures (p=0.001; p<0.01). The rate of mild displacement was significantly high among patients in the union group (p=0.001; p<0.01) (Table 2). Fifteen patients had negative union image on radiographs but had positive union image on CT scans.

All the 42 nondisplaced and ‘united’ fractures healed with up to 12 weeks of plaster immobilization, including 41 which removed the plaster at 4 weeks and mobilized.

DISCUSSION Scaphoid fractures are the most commonly reported fractures of the carpal bones. Nowadays, treatment using plasters is selected for nondisplaced fractures, whereas surgical treatment is preferred for displaced fractures. Nondisplaced fractures define fractures without 1 mm displacement. In previous studies, plasters were advised to be kept for 8–12 weeks in the treatment of scaphoid fractures. According to Desai et al.,[5] short-arm plasters should be performed for 8 weeks in patients with scaphoid waist fractures. Davis et al.[6] suggested that short-arm plasters should be kept for 12 weeks.

Geoghegan et al.[7] stated that 6 weeks of plaster treatment Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

is enough, but treatment should be performed using long-arm plasters. Clay et al.,[10] Hambidge et al.,[5] and McQueen et al.[11] have emphasized 8 weeks of short-arm plasters in the conservative treatment of nondisplaced scaphoid fractures.

In the literature, standard radiographs are commonly preferred for diagnosis and follow-up of scaphoid fractures. In the study performed by Low, fracture determination sensitivity with standard radiographs was defined as between 11% and 49%.[12] Bernard et al.[13] reported that the sensitivity of standard radiography in the determination of fracture displacement is low. Yin et al.[14] stated that magnetic resonance imaging (MRI) is the gold standard. However, there may be some problems to differentiate edema and trabecular collapse from a fracture on the MRI sections obtained just after trauma.

CT is an easily accessible and rapid imaging method. Singh reported that CT is the gold standard method for the determination of scaphoid union.[8] In evaluations performed by standard graphs, the fracture line may still be visible since the directed X-ray is parallel to the fracture line, which may cause the misdiagnosis as delayed union or non-union.[15] Fracture healing that was not observed in standard radiographs may be defined more clearly using CT scans. In our clinic, first, standard radiographs are obtained in patients with suspicion of scaphoid fractures. CT is obtained as an additional diagnos471

Çümen et al. Plaster treatment of nondisplaced scaphoid fractures

tic tool in patients without any detectable fractures in direct graphs who have positive findings on physical examination.

If the fracture is defined in standard radiographs, CT is also obtained in order to determine the displacement of fracture and to define the necessity of surgical treatment. CT is re-obtained at the end of 4 weeks to evaluate the healing process in fractures conservatively treated. In the present study, we observed a union rate of 97.6% in scaphoid fractures in CT evaluations obtained at the end of 4 weeks. In addition, we determined that the rate of non-union X-ray images to actual union in CT imaging was 35.7%. In many centers, owing to long-term plaster treatments, the joints of the patients are immobilized for a long term, causing loss of labor force. Since it is not easy to determine the union by standard radiographs, in order to eliminate the long-term plaster period, it would be more appropriate to evaluate the bone union using CT. If union will be determined by CT evaluations at the end of 4 weeks, the plasters may be removed safely, and a gentle physical treatment may be started.

Regarding fracture locations, union periods and non-union rates are also controversial in scaphoid fractures. Especially in proximal pole fractures, non-union is more commonly reported, and the follow-up period with plaster is advised to be long. Blood supply is inadequate in proximal pole, and for that reason, AVN and high non-union rates may be reported more commonly in fractures of this region. Regarding this, in clinical practice, long-term follow-up with plasters and more common surgical treatment approaches are present. Clay et al.[10] reported a non-union rate of 31% on seven patients with proximal pole scaphoid fractures. In the study by Grewal et al.[16] on six patients with proximal pole fractures who were followed up with CT, the non-union rate was reported as 50%. In our study, in three patients with nondisplaced proximal pole fractures who were treated with plaster, the union was determined on CT scans obtained at the end of 4 weeks. However, the union was determined on CT scans obtained at the end of 12 weeks in one patient with severe non-displacement proximal pole fractures who were treated with plaster. We believe that in those successful union results, early diagnoses and well differentiation of nondisplaced/ displaced fractures with CT resulting in preferring accurate treatment in relevant patients had some effects.

In our study, we also evaluated the displacement status, translation degree, and union surface rate between fracture fragments in CT evaluations obtained at the end of 4 weeks.

Regarding those results, the union rates were high in patients with minimal translation. When both groups were evaluated, there was a statistically significant difference regarding union at fracture line (p=0.001). Accordingly, high union rates were determined in patients with 75%–100% union at fracture line.

In addition, there was a statistically significant difference regarding displacement (p=0.001). Accordingly, the union rates were higher in patients with mild displacement on fracture line. In light of these data, we can conclude that mild dis472

placement, minimal translation, and high contact surface rates between fracture fragments would be the predictors of the union in patients. When the literature was investigated, in a similar study, Low et al. reported that translation degree, bone contact surface rate, and displacement status may be the predictors of the union, but there may be some differences between observers in evaluating those markers.[12]

Conclusion CT is a successful imaging technique in planning treatment of nondisplaced scaphoid fractures with plasters, and since it shows the union rates with high quality, we believe that it is a very effective tool in shortening plaster periods. In order to strengthen our results, randomized, controlled and larger studies are warranted.

Conflict of interest: None declared.

REFERENCES 1. Geissler WB, Adams JE, Bindra RR, Lanzinger WD, Slutsky DJ. Scaphoid fractures: what’s hot, what’s not. J Bone Joint Surg Am 2012;94:169–81.

2. Mack GR, Bosse MJ, Gelberman RH, Yu E. The natural history of scaphoid non-union. J Bone Joint Surg Am 1984;66:504–9.

3. Dias J, Kantharuban S. Treatment of Scaphoid Fractures: European Approaches. Hand Clinics 2017;33:501–9.

4. Winston MJ, Weiland AJ. Scaphoid fractures in the athlete. Curr Rev Musculoskelet Med 2017;10:38–44.

5. Hambidge JE, Desai VV, Schranz PJ, Compson JP, Davis TRC, Barton NJ. Acute fractures of the scaphoid. Treatment by cast immobilisation with the wrist in flexion or extension? J Bone Joint Surg Br 1999;81:91–2.

6. Davis EN, Chung KC, Kotsis SV, Lau FH, Vijan S. A cost/utility analysis of open reduction and internal fixation versus cast immobilization for acute nondisplaced mid-waist scaphoid fractures. Plast Reconstr Surg 2006;117:1223–5.

7. Geoghegan JM1, Woodruff MJ, Bhatia R, Dawson JS, Kerslake RW, Downing ND, et al. Undisplaced scaphoid waist fractures: is 4 weeks’ immobilisation in a below-elbow cast sufficient if a week 4 CT scan suggests fracture union? J Hand Surg Eur Vol 2009;34:631–7.

8. Singh HP, Forward D, Davis TR, Dawson JS, Oni JA, Downing ND. Partial union of acute scaphoid fractures. J Hand Surg Br 2005;30:440– 5.

9. Hackney LA, Dodds SD. Assessment of scaphoid fracture healing. Curr Rev Musculoskelet Med 2011;4:16–22.

10. Clay NR, Dias JJ, Costigan PS, Gregg PJ, Barton NJ. Need the thumb be immobilised in scaphoid fractures? A randomised prospective trial. J Bone Joint Surg Br 1991;73:828–32.

11. McQueen MM, Gelbke MK, Wakefield A, Will EM, Gaebler C. Percutaneous screw fixation versus conservative treatment for fractures of the waist of the scaphoid: a prospective randomised study. J Bone Joint Surg Br 2008;90:66–71.

12. Low G, Raby N. Can follow-up radiography for acute scaphoid fracture still be considered a valid investigation? Clin Radiol 2005;60:1106–10.

13. Bernard SA, Murray PM, Heckman MG. Validity of conventional radiography in determining scaphoid waist fracture displacement. J Orthop Trauma 2010;24:448–51.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Çümen et al. Plaster treatment of nondisplaced scaphoid fractures 14. Yin ZG, Zhang JB, Kan SL, Wang XG. Diagnostic accuracy of imaging modalities for suspected scaphoid fractures: meta-analysis combined with latent class analysis. J Bone Joint Surg Br 2012;94:1077–85.

15. Dias JJ. Definition of union after acute fracture and surgery for fracture

nonunion of the scaphoid. J Hand Surg Br 2001;26:321–5.

16. Grewal R, Lutz K, MacDermid JC, Suh N. Proximal Pole Scaphoid Fractures: A Computed Tomographic Assessment of Outcomes. J Hand Surg Am 2016;41:54–8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Nondeplase skafoid kırıkların alçı tedavisinde bilgisayarlı tomografi immobilizasyon süresini kısaltmaya yardımcı olur mu?

Dr. Hüseyin Çümen,1 Dr. Altuğ Duramaz,2 Dr. Cemal Kural2 1 2

Hakkari Devlet Hastanesi, Ortopedi ve Travmataloji Kliniği, Hakkari Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmataloji Kliniği, İstanbul

AMAÇ: Nondeplase skafoid kırıkların tedavisinde alçı süresi ile ilgili çelişkili sonuçlar bulunmaktadır. Bu çalışmanın amacı, nondeplase skafoid kırıkların tedavisinde iyileşme sürecini değerlendirmek ve bilgisayarlı tomografinin (BT) alçı süresinin kısaltılmasındaki rolünü belirlemekti.

GEREÇ VE YÖNTEM: Ocak 2012 ile Ocak 2014 arasında nondisplase skafoid kırığı tanısı alan 42 hasta değerlendirildi. Kırıklar anatomik yerleşim yerleri ve yer değiştirme derecelerine göre sınıflandırıldı. Kırıklar, nondeplase oldukları BT ile doğrulandıktan sonra başparmağı içeren kısa kol alçıya alındı. Radyolojik değerlendirme iki hafta aralıklar ile iki planlı grafiler kullanılarak yapıldı. Yaralanmanın dördüncü haftasında BT taramasında kemik iyileşmesine göre kaynama ve kaynamama gruplarına ayrıldılar. Kaynama grubundaki hastaların alçıları çıkarıldı.

BULGULAR: Anatomik yerleşim açısından sekiz hasta distal, 30’u bel bölgesi, dördü proksimal kırık olarak sınıflandırıldı. Ortalama yaşı 31.95±13.11 olan 42 hastanın 41’inde kırık iyileşmesi tespit edildi ve dördüncü hafta sonunda alçı çıkarıldı. Hastalar dördüncü haftanın sonunda kırık iyileşmesi bakımından kaynama ve kaynamama olmak üzere iki gruba ayrıldı. Translasyon derecesi, kontakt yüzey oranı ve yer değiştirme durumu açısından gruplar arasında istatistiksel olarak anlamlı farklılıklar vardı (sırasıyla, p=0.001, p=0.001 ve p=0.001).

TARTIŞMA: Nondeplase skafoid kırıklarının alçıyla takibinde BT ile yüksek kaynama oranlarının saptanması uzun süreli alçı tedavisinin gerekli olmadığını göstermiştir.

Anahtar sözcükler: Bilgisayarlı tomografi; kırık iyileşmesi; kısa dönem alçı tedavisi; skafoid kırıkları.

Ulus Travma Acil Cerrahi Derg 2018;24(5):468-473

doi: 10.5505/tjtes.2018.32069

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

473

ORIG I N A L A R T IC L E

Utility of the Three-Point Index in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures Zeki Taşdemir, M.D., Güven Bulut, M.D., Bilgehan Çevik, M.D., Engin Eceviz, M.D., Hüseyin Günay, M.D. Department of Orthopedics and Traumatology, Health Sciences University Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Forearm fractures constitute approximately 40% of all pediatric fractures. Generally, in conservative treatment,a plaster cast is applied with the elbow in 90° flexion. Success of the treatment depends on theprevention of the reduction in the correct position and suitable duration of the plaster cast. Failure, or the risk of angulation within the cast, is associated with movement within the cast. The aim of this study was to evaluate the applicability of the Cast Index (CI) and Three-Point Index (TPI) measurements, which indicate the loss of reduction, in pediatric mid-third forearm fractures. The hypothesis of the study was that as edema decreases and deformity of the plaster cast occurs after fracture reduction, TPI and CI should be examined during follow-up, as they indicate shifting due to movement within the plaster cast.

METHODS: This retrospective study included a total of 48 patients, who were treated with closed reduction and long-arm plaster cast for a mid-third forearm diaphyseal fracture at our Emergency Polyclinic between March and September 2014. The mean age of the patients was 8.15±3.19 years (range, 5–14 years). Patients were excluded from the study if they had isolated radial or ulnar fracture, open fractures, concomitant fracture or systemic disease (bone metabolism disease, etc), and <10° fracture angulation in the ulna and radius on the initial radiograph and if they did not followup. TPI and CI values were calculated on anterioposterior (AP) and lateral radiographs in the Picture Archiving Communication Systems.

RESULTS: In the AP plane, compared with TPI values after reduction, statistically significant increases were observed in TPI values 10 days after reduction (p<0.01). However, no significant difference was observed between those with and without reduction loss in TPI values in the AP plane (p>0.05). Although there was a statistically significant increase in TPI values 15 daysafter reduction compared with the values immediately after reduction, a significant difference between those with and without reduction loss was observed only on lateral TPI. CONCLUSION: In cases of pediatric forearm diaphyseal fracture, ulnar TPI examined in the lateral plane can be used in monitoring the fracture in a plaster cast applied after the reduction.

Keywords: Forearm fractures; pediatrics; Three-Point Index.

INTRODUCTION Forearm fractures constitute approximately 40% of all pediatric fractures. Generally, conservative treatment involves theapplication of a plaster cast with the elbow in 90° flexion.

[1,2] The success of the treatment depends on the protection

of the reduction in the correct position and suitable duration of the plaster cast.[3,4] Failure, in other words the risk of angulation within the cast, is associated with movement within the cast. No correlation has been shown between the failure and fracture type, location of the fracture, and sex of the patient.[5]

Cite this article as: Taşdemir Z, Bulut G, Çevik B, Eceviz E, Günay H. Utility of the Three-Point Index in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures. Ulus Travma Acil Cerrahi Derg 2018;24:474-480.

Address for correspondence: Zeki Taşdemir, M.D. Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul, Turkey Tel: +90 216 - 441 39 00 E-mail: drtazeki@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):474-480 DOI: 10.5505/tjtes.2018.84553 Submitted: 03.11.2016 Accepted: 07.03.2018 Online: 10.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

474

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Taşdemir et al. Utility of the TPI in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures

The aim of this study was to evaluate the applicability of the Cast Index (CI) and Three-Point Index (TPI) measurements, which indicate the loss of reduction, in pediatric mid-third forearm fractures. The hypothesis of the study was that as edema and deformity of the plaster cast decreases after fracture reduction, TPI and CI are parameters that should be examined during follow-upbecause they indicate shifting due to movement within the plaster cast.

MATERIALS AND METHODS This retrospective study included a total of 48 patients, who were treated with closed reduction and long-arm plaster cast for a mid-third forearm diaphyseal fracture at our Emergency Polyclinic between March and September 2014. The mean age of the patients was 8.15±3.19 years (range, 5–14 years).

Patients with an isolated fracture of the radius in four cases, isolated fracture of the ulna in three cases, open fracture in four cases, concomitant fracture in the same upper extremity in two cases, a systemic disease (bone metabolism disease, etc.) in one case, non-displaced fractures (<10° fracture angulation in the ulna and radius on the initial radiograph) in five cases, open reduction and internal fixation applied on the 3rd day in onecase, and no appropriate followup in one case.

In the classification of the fracture location, the distance between the distal epiphysis of the radius and the proximal epiphysis was divided into threeequal parts and fractures in the mid-third were accepted as diaphyseal fractures (Fig. 1a).

Following reduction, a long-arm plaster cast extending from the middle of the arm to the metacarpophalangeal joints with the elbow in 90° flexion and the forearm in a neutral position was applied to all patients. Monitoring of the reduction within the plaster cast was made by accepting <10° angulation and >50% contact of the radial and ulnar fracture on AP and lateral radiographs as sufficient (Fig. 1b).[1] (a)

(b)

(c)

In the control, X-ray was taken 15 days after the reduction of >5° angulation, which was compared with the first X-ray taken after fracture reduction, and lack of contact surface was considered as loss of reduction. In fractures with no contact surface, where an increase of >5° angulation was seen, they were excluded without evaluation of the contact surface. The measurements were calculated on the AP and lateral radiographs in the Picture Archiving Communication Systems (PACS). Fracture classifications and fracture angulations were evaluated by orthopedic specialists.

TPI and CI values were calculated on the AP and lateral radiographs in PACS. On the AP radiograph, with the measurements of the space between the plaster cast and soft tissue on the radial side at the level of the distal epiphyseal line of the radius (a), the space on the ulnar side in the fracture line (b), the space on the radial side at the level of the beginning of the radial tubercle (c), and the total external diameter of the proximal radius at the level of the fracture line (d), the radial TPI was calculated as (a+b+c)/d. On the AP radiograph, with the measurements of the space between the plaster cast and soft tissue on the ulnar side at the level of the distal epiphyseal line of the radius (a), the space on the radial side in the fracture line (b), the space on the ulnar side at the level of the beginning of the radial tubercle, (c) and the total external diameter of the proximal ulna at the level of the fracture line (d), the ulnar TPI was calculated as a+b+c/d. On the lateral radiograph, the radial TPI measurement was obtained taking the (a) and (c) distances from the volar side and the (b) distance from the dorsal side and the ulnar TPI measurement taking the (a) and (c) distances from the dorsal side and the (b) distance from the volar side (Fig. 1c).

CI values were calculated on the AP and lateral radiographs with the measurements of the distance between soft tissues in the radial and ulnar fracture line (q) and the distance between the plaster (w) as q/w. The ulnar CI was calculated according to the measurements made from the ulnar fracture line and radial CI from the measurements in the radial fracture line (Fig. 1d). (d)

Figure 1. (a) Identification of the fracture location. (b) Angulation on lateral radiography. (c) TPI calculations. (d) CI calculations.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

475

Taşdemir et al. Utility of the TPI in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures

The inter- and intra-observer reliability of TPI measurements was evaluated by two orthopedic specialists repeating the measurements on the same radiographs 20 days after the first measurements.

IBM SPSS 22.0 software was used for the evaluation of the findings obtained in the study. The conformity of the study data to normal distribution was evaluated with the Kolmogorov–Smirnov test, and the data were determined to conform to the normal distribution of the parameters. In addition to descriptive statistical methods (mean, standard deviation), in the comparison of quantitative parameters between two groups, Student’s t-test was used. In the comparison of changes observed in the measurements made 15 days after reduction, the paired samples t-test was used. Pearson’s correlation analysis was applied in the examination of correlations between the parameters. A p value of <0.05 was accepted as statistically significant. The intraclass correlation coefficient (ICC) was used for the analysis of intra-observer and inter-observer reliability.

RESULTS The mean age of the patients was 8.15±3.19 years (range, 5–14 years). Of the total 48 cases, the fracture was on the right arm in 24 cases and on the left arm in 24 cases. On initial radiographs, >15° angulation was determined on the lateral radiograph in 32 cases and on the AP radiograph in 27 cases. Reduction loss was observed in the lateral plane in 12 cases, in the AP plane in 5 cases, and in both the AP and lateral planes in 7 cases. When the cases with reduction loss were examined, it was seen that on all the initial radiographs, there was angulation of >15° in at least one of the ulnar or radial fracture lines (Table 1).

In both the ulnar and radial TPI measurements, a statistically significant increase was observed in the TPI measurements on the 15th day compared with the measurements taken after reduction in both the AP and lateral planes (p<0.01) (Table 2).

According to the reduction loss seen on the AP radiographs, no statistically significant difference was determined between the ulnar and radial TPI measurements after reduction and on the 15th day (p>0.05). Also, according to the reduction loss seen on the AP radiographs, no statistically significant difference was determined between the ulnar and radial CI measurements after reduction and on the 15th day (p>0.05) (Table 3).

In the group in which no reduction loss was seen on the AP radiographs, a statistically significant difference was determined between the ulnar and radial TPI measurements after reduction and on the 15th day (p=0.001). Furthermore, in the group in which reduction loss was observed on the AP radiographs, a statistically significant difference was determined between the ulnar and radial TPI measurements after reduction and on the 15th day (p=0.004, p=0.007) (Table 3).

476

Table 1. Distribution of general characteristics

Number of patients

n %

Side Right

24 50

Left

24 50

>15° angulation on initial AP radiograph Absent

21 43.8

Present

27 56.2

>15° angulation on initial lateral radiograph Absent

12 25

Present

36 75

Reduction loss None

24 50

On lateral radiograph only

12

25

On AP radiograph only

5

10.4

On both AP and lateral radiographs

7

14.6

AP: Anterioposterior.

Table 2. Evaluation of the TPI measurements on the AP and lateral radiographs

After reduction

15th day

Mean±SD

Mean±SD

p

AP

Radial TPI

1.01±0.44

1.21±0.40

0.001**

Ulnar TPI

1.11±0.39

1.40±0.52

0.001**

Lateral

Radial TPI

1.08±0.37

1.50±0.49

0.001**

Ulnar TPI

1.09±0.36

1.44±0.47

0.001**

Paired samples t-test **p<0.01. AP: Anterioposterior; TPI: Three Point Index; SD: Standard deviation.

According to the reduction loss seen on the AP radiographs, no statistically significant difference was determined between the ulnar and radial TPI measurements after reduction and on the 15th day (p>0.05) (Table 4).

According to the reduction loss seen on the lateral radiographs, no statistically significant difference was determined between the ulnar and radial TPI and CI measurements after reduction and on the 15th day (p>0.05).

In cases in which reduction loss was seen on the lateral radiographs, ulnar TPI measurements on the 15th day were determined to be significantly higher than those in cases in which no reduction loss was observed (p<0.05). According to observed on lateral radiographs, no statistically significant Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Taşdemir et al. Utility of the TPI in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures

Table 5. Evaluation of TPI and CI measurements according to the reduction loss seen on the lateral radiographs

Table 3. Evaluation of the TPI and CI measurements

according to the reduction loss seen on the AP radiographs

Reduction loss on AP radiograph

Absent

Present

Mean±SD

Mean±SD

p

Reduction loss on AP radiograph

p

1

1

Absent

Present

Mean±SD

Mean±SD

1.04±0.39

1.16±0.34

0.269

1.41±0.47

1.65±0.49

0.110

Radial TPI Radial TPI

After reduction

15th day

0.97±0.29

0.745

15 day

1.22±0.43

1.19±0.32

0.847

p 0.001** 0.007**

2

After reduction

15th day

15 day

1.44±0.53

1.29±0.47

0.381

1.12±0.16

1.15±0.17

0.522

Ulnar CI

1.12±0.15

1.14±0.17

0.635

Student’s t-test; 2Paired samples t-test; **p<0.01. AP: Anterioposterior; TPI: Three Point Index; CI: Cast Index; SD: Standard deviation.

1

Table 4. Evaluation of the radial and ulnar TPI measurements at 15 days compared to with those immediately after reduction according to the reduction loss seen on the AP radiographs Reduction loss on AP radiograph

Absent

Present

Mean±SD

Mean±SD

p

1

Radial TPI

immediately after

reduction and

15th day

After reduction

0.381

Radial CI

Difference between

p 0.001** 0.001**

1.02±0.32

p 0.001** 0.004**

2

1.13±0.41

2

th

Ulnar TPI

Ulnar TPI

After reduction

1.02±0.48

th

2

1.19±0.33

0.118

1.33±0.37

1.61±0.56

0.043*

p 0.001** 0.002**

Radial CI

1.11±0.16

1.15±0.16

0.395

Ulnar CI

1.11±0.16

1.15±0.15

0.394

1 Student’s t-test; 2Paired samples t-test; *p<0.05; **p<0.01. AP: Anterioposterior; TPI: Three Point Index; CI: Cast Index; SD: Standard deviation.

Table 6. Evaluation of the radial and ulnar TPI measurements immediately after reduction and on the 15th day according to the reduction loss seen on the lateral radiographs

Reduction loss on lateral radiograph

p

Absent

Present

Mean±SD

Mean±SD

0.37±0.27

0.48±0.43

0.274

0.31±0.23

0.43±0.50

0.343

Radial TPI

0.19±0.32

0.21±0.22

0.825

Difference between

immediately after

reduction and

15th day

Ulnar TPI

Ulnar TPI

Difference between

Difference between

immediately after

immediately after

reduction and

reduction and

15th day

1.02±0.36

0.31±0.37

0.27±0.26

0.742

15th day

Student t-test. AP: Anterioposterior; TPI: Three Point Index; SD: Standard deviation.

Student t-test. AP: Anterioposterior; TPI: Three Point Index; SD: Standard deviation.

difference was determined between radial TPI measurements on the 15th day (p>0.05) (Table 5).

lateral radiographs, the radial and ulnar TPI measurements on the 15th day were determined to be significantly higher than the measurements after reduction (p=0.001).

In the group in which no reduction loss was observed on the lateral radiographs, the radial and ulnar TPI measurements on the 15th day were determined to be significantly higher than the measurements after reduction (p=0.001). Furthermore, in the group in which reduction loss was observed on the Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

According to the reduction loss observed on the lateral radiographs, no statistically significant difference was determined between the ulnar and radial TPI measurements after reduction and on the 15th day (p>0.05) (Table 6).

477

Taşdemir et al. Utility of the TPI in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures

Table 7. Correlations between TPI and CI measurements

Radial CI

Ulnar CI

r r

AP radial TPI

0.336* –

Lateral radial TPI

0.233

–

AP ulnar TPI

–

0.285*

Lateral ulnar TPI

–

0.205

Pearson’s correlation coefficient *p<0.05. TPI: Three Point Index; CI: Cast Index.

Table 8. Inter-observer reliability of the lateral radial TPI measurements

Observer 1- Observer 2

ICC (95% CI)

1st measurement

0.997** (0.992/0.999)

2nd measurement

0.998** (0.994/0.999)

p<0.01. ICC: Intraclass correlation coefficient; TPI: Three Point Index.

**

Table 9. Intra-observer reliability for the first and second measurements of the lateral radial TPI 1st measurement-2nd measurement

ICC (95% CI)

Observer 1

0.997 (0.992/0.999)

Observer 2

0.999 (0.996/0.999)

p<0.01. ICC: Intraclass correlation coefficient; TPI: Three Point Index.

**

On the AP radiographs, a statistically significant correlation was determined in the same direction between the radial CI and radial TPI measurements (p<0.05) at the level of 33.6%.

As the radial CI measurements increased, so did the radial TPI measurements. On the AP radiographs, a statistically significant correlation was determined in the same direction between the ulnar CI and ulnar TPI measurements (p<0.05) at the level of 28.5%. As the ulnar CI measurements increased, so did the ulnar TPI measurements. While the ulnar and radial TPI and CI measurements were seen to be in parallel on the AP radiographs, TPI and CI measurements on the lateral radiographs were not consistent (Table 7).

When the lateral radial TPI measurements were examined, statistical reliability was determined between the two observers (p<0.01) (Table 8).

When the lateral radial TPI measurements of Observer 1 were examined, statistical reliability was determined between the first and second measurements (p<0.01). When the lat478

eral radial TPI measurements of Observer 2 were examined, statistical reliability was determined between the first and second measurements (p<0.01) (Table 9).

The inter- and intra-observer ICC reliability of the TPI measurements was observed to be high (95% CI) (Tables 8 and 9).

DISCUSSION In the follow-up of pediatric forearm fractures with closed reduction and plaster cast, several factors affect reduction loss.

[6] Initial fracture angulation occurring at the time of trauma is one of the most important factors affecting reduction loss.[6] This angulation can give an idea of the severity of the trauma and whether or not the periosteum is torn. In the current study, all the cases with reduction loss were seen to have >15° angulation in the fracture line on the initial radiograph taken after the trauma (before reduction). Severe soft tissue trauma may cause excessive swelling, which loosens the plaster cast, and this may result in an increased risk of reduction loss. Anatomic reduction and fixation of the reduction in completely displaced fractures are rarely successful.[4,7,8] In the current study, an increase was determined in both the TPI and CI measurements on the 15th day, which supports the hypothesis that as soft tissue edema decreases, the plaster cast is loosened.

In general, reduction loss is accepted as >10° angulation toward the dorsal or volar side, >5° radial or ulnar angulation, or >3 mm translation. There are also physicians who accept reduction loss as 2-mm translation in addition to 5° volar or dorsal angulation.[9] In the current study, reduction loss was evaluated as an increase of >5° in fracture angulation or no surface contact. We believe that translation should be measured as a ratio in forearm fractures. As increases in fracture angulation of <5° can show variations in individual measurements, increases in fracture angulation of >5° were evaluated in this study.

Mazzini et al.[10] showed that reduction loss was common in their series involving 161 cases of distal radial metaphyseal fractures. They advocated that reducing the post-reduction translation was the most important predictor of preventing reduction loss.

In the follow-up of distal radius fractures with plaster casting, the CI, Padding Index, Gap Index, and TPI have been described. The TPI is an extremely valuable measurement withrespect to predicting the re-displacement of distal radius fractures.[11] In the current study, it was aimed to identify the possibility of reduction loss in pediatric forearm fractures using TPI. The findings of the study show that ulnar TPI in the lateral plane can be used for this purpose. That TPI measurements in the AP plane in particular were higher in those with reduction loss than in those without reduction loss can be considered to be due to less soft issue in the AP plane and Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Taşdemir et al. Utility of the TPI in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures

that the ligamentous structures between the radius and ulna are seen in the AP plane.[12]

to be as important as the quality of the plaster cast in the effect on reduction loss.

Iltar et al.[13] showed that in 71 fractures (93%), TPI correctly predicted that there would be re-manipulation with 84% sensitivity, 97% specificity, 89% positive predictive value, and 95% negative predictive value. There were three false-negative and two false-positive results. In both the false-negative results, banana-type elbow molding was applied. These results suggest that lateral radiography is more valuable in forearm fractures that were truly casted.

Conflict of interest: None declared.

Children were divided into three groups according to age: 1st group: <5 years, 2nd group: 5–10 years, and 3rd group:>10 years. When the sensitivity and specificity of CI was high to predict the re-manipulation of displaced distal forearm fractures in children of all age groups, the cut-off point for intraoperative CI was 0.84. Elevated CI (≥0.84) in post-manipulation radiographs showed the increased risk of displacement, especially in fractures in patients aged <5 and >10 years. In our study, the ulnar and radial TPI and CI measurements were seen to be compatible on AP radiographs, but the TPI and CI measurements on the lateral radiographs were not consistent.[14] In those with reduction loss, the ulnar TPI measured in the lateral plane was high and the measurability of the ulnar TPI in the lateral plane was found to be statistically significant.

However, the ulnar TPI results in the lateral plane were not calculated with cut-off values because of the low number of cases. In addition, the high (1.33±0.37) value of the ulnar TPI in the lateral plane in cases with no reduction loss on the 15th day can be considered to be the reason for the cut-off values not having been calculated.

The most important limitation of this study is that it was retrospective and there were few cases determined with reduction lossduring the follow-up period. A prospective study with a greater number of cases of pediatric forearm fractures would be able to calculate TPI or CI with cut-off values. Additionally, the study could be evaluated with a control group by changing the plaster cast within 10 days, those with reduced TPI. Several authors have emphasized that quality and weakness of the plaster cast are among the risk factors for reduction loss.

[5,8,15–18] Alemdaroğlu et al.[19] reported that TPI is more sensitive and specific than other radiological indexes. On the basis of the opinion of Alemdaroğlu et al. that TPI is more sensitive, the current study focused more on TPI. Based on the results of this study, it was concluded that in cases of pediatric forearm diaphyseal fracture, in the monitoring of the fracture within a plaster cast applied after the first reduction, ulnar TPI examined in the lateral plane can be used on the 15th day.

In conclusion, in pediatric forearm diaphyseal fractures, which have achieved sufficient reduction, several factors can be held Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

REFERENCES 1. Noonan KJ, Price CT. Forearm and distal radius fractures in children. J Am Acad Orthop Surg 1998;6:146–56.

2. Tachdjian MO. Fractures of the shaft of the radius and ulna. In: Paediatric Orthopaedics. 2nd ed. Philadelphia: WB Saunders Comp; 1990. p.

3181–201.

3. Voto SJ, Weiner DS, Leighly B. Redisplacement after closed reduction of forearm fractures in children. J Pediatr Orthop 1990;10:79–84.

4. Proctor MT, Moore DJ, Paterson JM. Redisplacement after manipulation of distal radial fractures in children. J Bone Joint Surg Br 1993;75:453–4.

5. Bhatia M, Housden PH. Re-displacement of paediatric forearm fractures: Role of plaster moulding and padding. Injury 2006;37:259–68.

6. Mani GV, Hui PW, Cheng JC. Translation of the radius as a predictor of outcome in distal radial fractures of children. J Bone Joint Surg Br 1993;75:808–11.

7. Jordan RW, Westacott DJ. Displaced paediatric distal radius fractures-when should we use percutaneous wires? Injury 2012;43:908–11.

8. McQuinn AG, Jaarsma RL. Risk factors for redisplacement of pediatric distal forearm and distal radius fractures. J Pediatr Orthop 2012;32:687– 92.

9. Asadollahi S, Ooi KS, Hau RC. Distal radial fractures in children: risk factors for redisplacement following closed reduction. J Pediatr Orthop 2015;35:224–8.

10. Mazzini JP, Beck N, Brewer J, Baldwin K, Sankar W, Flynn J. Distal metaphyseal radius fractures in children following closed reduction and casting: can loss of reduction be predicted? Int Orthop 2012;36:1435–40.

11. Martin JR. Paediatric forearm and distal radius fractures: Risk factors and redisplacement-role of casting indices. Int Orthop 2010;34:407–12.

12. McKinley MP, O’Loughlin VD. Human Anatomy. 3rd ed. McGrawHill; 2012. p. 225–30.

13. Iltar S, Alemdaroğlu KB, Say F, Aydoğan NH. The value of the threepoint index in predicting redisplacement of diaphyseal fractures of the forearm in children. Bone Joint J 2013;95:563–7.

14. Debnath UK, Guha AR, Das S. Distal forearm fractures in children: cast index as predictor of re-manipulation. Indian J Orthop 2011;45:341–6.

15. Alemdaroğlu KB, Iltar S, Cimen O, Uysal M, Alagöz E, Atlıhan D. Risk factors in redisplacement of distal radial fractures in children. J Bone Joint Surg Am 2008;90:1224–30.

16. Devalia KL, Asaad SS, Kakkar R. Risk of redisplacement after first successful reduction in paediatric distal radius fractures: sensitivity assessment of casting indices. J Pediatr Orthop B 2011;20:376–81.

17. Webb GR, Galpin RD, Armstrong DG. Comparison of short and long arm plaster casts for displaced fractures in the distal third of the forearm in children. J Bone Joint Surg Am 2006;88:9–17.

18. Chess DG, Hyndman JC, Leahey JL, Brown DCS, Sinclair AM. Short arm plaster cast for distal pediatric forearm fractures. J Pediatr Orthop 1994;14:211–3.

19. Alemdaroğlu KB, Iltar S, Aydoğan NH. 3-point index in redisplacement of distal radial fractures in children: how should it be used? J Hand Surg Am 2009;34:964.

479

Taşdemir et al. Utility of the TPI in the determination of reduction loss during the conservative treatment of pediatric forearm mid-third fractures

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Çocuk önkol orta 1/3 kırıklarının konservatif tedavisi sırasında redüksiyon kaybının saptanmasında “Three Point Index”in kullanılabilirliği Dr. Zeki Taşdemir, Dr. Güven Bulut, Dr. Bilgehan Çevik, Dr. Engin Eceviz, Dr. Hüseyin Günay Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul

AMAÇ: Önkol kırıkları çocuk kırıklarının yaklaşık %40’ını oluşturur. Genel olarak dirsek 90˚ fleksiyonda alçılama yapılarak konservatif olarak tedavi edilir. Tedavinin başarısı redüksiyonun doğru pozisyonda korunmasına ve alçılamayı zamanında sonlandırmaya bağlıdır. Başarısızlık, yani alçı içerisinde açılanma oluşma riski, alçı içindeki harekete bağlıdır. Bu çalışmanın amacı, redüksiyon kaybını işaret eden “Cast Index” (CI) ve “Three Point Index” (TPI) ölçümünün çocukların önkol orta 1/3 kırıklarında uygulanabilirliğinin araştırılmasıdır. Hipotezimiz kırık redüksiyonu sonrası ödemin azalması ve alçının deforme olması nedeniyle, alçı içerisinde harekete bağlı kaymayı işaret eden TPI ve CI’inin takipler sırasında bakılması gereken parametreler olduğudur.

GEREÇ VE YÖNTEM: Çalışma geriye dönük olarak planlandı. 2014 yılı Mart–Eylül ayları arasında acil polikliniğimizde 1/3 orta önkol diyafiz kırığı kapalı redüksiyon ve uzun kol alçı tespiti ile tedavi edilen 48 olgu çalışmaya dahil edildi. Hastaların yaşları beş ile 14 (8.15±3.19) arasında değişmekte idi. Sadece radiusu veya sadece ulnası kırık olanlar, açık kırıklar, ek kırığı ya da sistemik hastalığı (kemik metabolizma hastalığı, vb) olanlar, geliş grafisinde ulna ve radiusta 10°’den az kırık açılanması olanlar ve uygun takibi yapılamayan hastalar çalışmadan çıkarıldı. “Picture Archiving Communication Systems” (PACS) üzerinde anteroposterior (AP) ve lateral grafilerde TPI ve CI hesaplandı.

BULGULAR: Anteroposterior planda redüksiyon sonrası yapılan TPI ölçümlerine göre, redüksiyondan 10 gün sonra yapılan TPI ölçümlerinde saptanan artışlar istatistiksel olarak anlamlı idi (p<0.01). Ancak AP planda redüksiyon kaybı olanlar ile olmayanların redüksiyon sonrası TPI ölçümleri arasında istatistiksel olarak anlamlı farklılık bulunmadı (p>0.05). Redüksiyon kaybı olanlar ile olmayanların AP planda CI ölçümleri arasında da istatistiksel olarak anlamlı farklılık yoktu (p>0.05).

TARTIŞMA: Redüksiyondan 15. günde ölçülen TPI değerlerinde redüksiyon sonrası TPI değerlerine göre anlamlı artış olmasına rağmen, redüksiyon kaybı olanlar ile olmayanlar arasında anlamlı fark sadece lateral TPI’de gösterildi.

Anahtar sözcükler: Çocuk; önkol kırıkları; Three Point Index.

Ulus Travma Acil Cerrahi Derg 2018;24(5):474-480

480

doi: 10.5505/tjtes.2018.84553

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

EXPERIMENTAL STUDY

Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats Özgür Kardeş, M.D.,1 Soner Çivi, M.D.,1 Erkut Baha Bulduk, M.D.,2 Halil İbrahim Süner, M.D.,1 Emre Durdağ, M.D.,1 Kadir Tufan, M.D.1

Fazilet Kaya Selçuk, M.D.,3

1

Department of Neurosurgery, Başkent University Faculty of Medicine Adana Turgut Noyan Application and Research Center, Adana-Turkey

2

Department of Neurosurgery, Eskişehir Government Hospital, Eskişehir-Turkey

3

Department of Pathology, Başkent University Faculty of Medicine Adana Turgut Noyan Application and Research Center, Adana-Turkey

ABSTRACT BACKGROUND: The aim of our study is to minimize the morbidity related to nerve injury by determining the protective effects of gabapentin in experimental sciatic nerve injury and end-to-end anastomosis model in rats and to guide clinical studies on this subject.

METHODS: In our study, 40 adult male Sprague–Dawley rats were randomly divided into the following five groups: I: Only surgical intervention was applied; II: The sciatic nerve was cut properly and was repaired by end-to-end anastomosis. No additional procedure was performed; III: A single dose of gabapentin at 30 mg/kg was given after anastomosis; IV: 30 mg/kg gabapentin was given for 3 days after anastomosis; and V: 30 mg/kg gabapentin was given for 7 days after anastomosis. The experiment was terminated with high-dose thiopental (50 mg/kg) 60 days after the surgical intervention. The right sciatic nerve was taken from all animals. The obtained sections were examined immunohistopathologically.

RESULTS: Immunohistochemical properties and Schwann cell proliferation were found to be statistically significantly lower in the control group than in the other groups. Schwann cell proliferation was higher in Group 3 than in Group 5. Immunohistochemical changes were significantly lower in Group 4 than in Group 3. Axonal degeneration was also higher in Group 4 than in Group 3.

CONCLUSION: Gabapentin promotes neurological recovery histopathologically in peripheral nerve injury due to its neuroprotective properties. Our study results show that gabapentin can be used as an adjunctive therapy to primary surgical treatment after peripheral nerve injury.

Keywords: Anastomosis; gabapentin; peripheral nerve; sciatic nerve; trauma.

INTRODUCTION The statement “Once nerves are cut, they cannot be repaired” was accepted by many surgeons until the 20th century.

[1] First, in the 9th and 10th centuries, Arab surgeons began to suture peripheral nerve cuts.[2] When we look at the nerve graft techniques, we see that the first description was given

by Gabriele Ferrara in the 17th century and that the stitches had been thrown with a tendon that was laid with red wine.[1] Peripheral nerve injuries can occur due to mechanical, chemical, and thermal reasons. Trauma is the most common rea-

son. Nowadays, it is known that peripheral nerve injury occurs in 2.8% of trauma patients.[3] The aim of surgical treatment in peripheral nerve injuries is to ensure that the axons remain proximal to a transection so that they can reach their original distal ends during regeneration and innervate the end organs.[4] Currently accepted treatments in peripheral nerve injuries are as follows: 1) early end-to-end nerve repair for nerve transection injury and 2) graft repair when there are large gaps or tensions between damaged nerve endings.[5] In pe-

Cite this article as: Kardeş Ö, Çivi S, Bulduk EB, Kaya Selçuk F, Süner Hİ, Durdağ E, et al. Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats. Ulus Travma Acil Cerrahi Derg 2018;24:481-487.

Address for correspondence: Erkut Baha Bulduk, M.D. Adres bilgisi: Eskişehir Devlet Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, Eskişehir, Turkey Tel: +90 222 - 237 48 00 E-mail: erkutbahabulduk@hotmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):481-487 DOI: 10.5505/tjtes.2018.66712 Submitted: 14.05.2018 Accepted: 12.09.2018 Online: 10.10.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

481

Kardeş et al. Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

ripheral nerve repair, tension on the neural tissues is an undesired situation. Studies on this subject show that an average of more than 10% tension applied to nerve endings to close the defect causes up to a 50% reduction in blood flow.[6] The failure of peripheral nerve repair leads to motor and sensory deficits and painful neuropathies in the target muscle. The gold standard treatment for peripheral nerve injury is primary end-to-end repair of two transected peripheral nerve endings; if this cannot be performed, nerve endings are connected to each other using autologous sensory nerve graft.[7] Peripheral nerve injuries were classified into three major groups according to clinical condition and microscopic changes after nerve injury by Seddon in 1943: neurapraxia, axonotmesis, and neurotmesis. Then, Sunderland expanded this classification from three to five degrees of peripheral nerve injury according to the severity of nerve injury (Table 1).[8–10] These simple classifications are still currently used, especially for the follow-up and treatment of acute nerve injuries.[11] Gabapentin, which has entered into clinical use as an adjuvant anticonvulsant drug in the treatment of partial seizures in 1993, is widely used for neuropathic pain, migraine, and spasticity today.[12–14] The antinociceptive, anticonvulsant, anxiolytic, and neuroprotective effects of gabapentin have been shown in various animal models.[15] It has been suggested that the neuroprotective effects of gabapentin may be related to changes in glutamate synthesis and metabolism.[13,16] There are many studies investigating its neuroprotective effects in cerebral ischemia, cerebral trauma, spinal cord trauma, and peripheral nerve injury.

In the literature, to the best of our knowledge, there is no any study on the efficacy of gabapentin in peripheral nerve anastomosis.

The aim of this study was to examine the effects of gabapentin on nerve healing after an experimental rat sciatic nerve transection was surgically repaired.

MATERIALS AND METHODS The experimental protocol of our study was examined and approved by the Ethical Committee of Baskent University Medical and Health Sciences (Decision Date: 18/09/2015; Decision No: DA15/40). Our study was supported by the Baskent University Research Fund.

The animals used in the study were obtained from the Baskent University Experimental Animal Breeding Laboratory. All the experimental steps of the study were performed in the Baskent University Experimental Animal Research Laboratory. Immunohistochemical examinations were completed in the Department of Pathology at Baskent University.

Animals Forty male Sprague–Dawley rats (250–300 g; 12 weeks of age) were used in our study. The rats were kept at room temperature in a 12-hour light/12-hour dark cycle in the laboratory environment for 60 days. All rats had free access to food and water. On the 60th day of the study, the animals were sacrificed to obtain samples for immunohistochemical examinations.

Groups and Surgical Procedures In our study, rats were randomly assigned into five groups. All rats were administered xylazine 10 mg/kg (Rompun, Bayer) and ketamine 60 mg/kg (Ketalar, Pfizer) for anesthesia intraperitoneally before surgery.

All surgical procedures were performed by a single surgeon.

Surgical procedures were applied to the right sciatic nerve of the rats.

Subsequently, subjects were fixed at the prone position, four extremities and their teeth on the wooden operation table with the band.

Group I (Control) (n=8): After the administration of anesthesia, the right hind limbs were prepared for surgery using a sterile technique. Skin incision was followed by dissection of the gluteal muscles to expose the sciatic nerve, including the tibial, peroneal, and sural branches, under a surgical micro-

Table 1. Seddon and Sunderland classification of peripheral nerve injury Seddon’s classification

Sunderland’s classification

Injured tissues

Neurapraxia

Grade I

Myelin

Axonotmesis

GradeII

Myelin, axon

Neurotmesis

Grade III

Myelin, axon, endoneurium

Grade IV

Myelin, axon, endoneurium, perineurium

Grade V

Myelin, axon, endoneurium, perineurium epineurium

Source 8–10.

482

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Kardeş et al. Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

sections taken from the paraffin blocks were immunohistochemically stained with anti-CACNA2D1 antibody (Abcam cat:2864) as the primary antibody and with rabbit Antimouse IgG (Abcam) as the secondary antibody. The results were scored semiquantitatively (0, absent, 1, mild; 2, moderate; 3, strong).

Statistical Methods The IBM SPSS 24.0 statistic software (IBM Corporation Armonk, NY, USA) was used to analyze the variables. The Kruskal–Wallis H test was used to compare more than two groups with each other according to quantitative data. The Dunn’s test was used for post-hoc analysis.

Figure 1. Image of sciatic nerve that was end to end anastomosed.

scope (Opmi 9-FC, Carl Zeiss AG, Germany). This group’s sciatic nerves were only dissected under general anesthesia.

No incision or anastomosis of the sciatic nerve was conducted.

Group II (n=8): In addition to the surgical procedures described in Group I, end to end (ETE) anastomosis of the proximal and distal stumps was performed after sectioning the sciatic nerve. Anastomoses were performed using 10–0 nylon sutures. No additional treatment was applied to this group of animals (Fig. 1).

Group III (n=8): In addition to the surgical procedures described in Group II, 30 mg/kg gabapentin was administered intraperitoneally to the animals in a single dose (4 h posttreatment).

Group IV (n=8): In addition to the surgical procedures described in Group II, the animals were applied 30 mg/kg gabapentin intraperitoneally for 3 days.

Group V (n=8): In addition to the surgical procedures described in Group II, the animals were applied 30 mg/kg gabapentin intraperitoneally for 7 days.

Quantitative variables were shown as median and range (maximum–minimum) in tables. These variables were examined at a 95% confidence level. A p-value of less than 0.05 was considered statistically significant.

RESULTS When Schwann cell proliferation was evaluated according to the groups, there was a statistically significant difference (p<0.001). The median value of Schwann cell proliferation was lower in Group 1 (0 [0/0]) than in Groups 2, 3, 4, and 5 (respectively, 1.08 [0/2]; 1.56 [1/2]; 1.07[0/2]; and 0.86 [0/2]). This difference was statistically significant (all p-values <0.001). Moreover, the median value of Schwann cell proliferation was higher in Group 3 (1.56 [1/2]) than in Group 5 (0.86[0/2]). This difference was statistically significant (p=0.008). There were no significant differences between other groups (p>0.05).

When axonal degeneration was evaluated according to the groups, there was a statistically significant difference (p<0.001). The median value of axonal degeneration was higher in Group 4 (1.75 [1/2]) than in Group 3 (1.07 [0/2]).

The median value of axonal degeneration was lower in Group 5 (1.07 [0/2]) than in Group 4 (1.75 [1/2]). These differences were statistically significant (p<0.001).

Immunohistochemical Evaluation

The median value of inflammation was found to be the same in Group 1 (control group) (0.13 [0/1]) and in Groups 4 and 5 (respectively, 0.13 [0/1] and 0.13 [0/1]). There was no statistically significant difference between these groups (p>0.05).

Sciatic nerves dissected from the rats were fixed in 10% buffered formaldehyde. After a routine tissue process, the samples were embedded in paraffin blocks, and 5-mm-thick sections were cut axially using a microtome (RM 2245, Leica) for hematoxylin and eosin (H&E) staining. Slides were evaluated under a light microscope (DMI 4000 B Leica) by a pathologist who was blinded to the groups. The presence of the Schwainan cells, inflammation, and axonal degeneration were evaluated and scored semiquantitatively (0, absent; 1, mild; 2, moderate; 3, severe/marked). Four micron-thick

When we evaluated immunohistochemical changes, there was a statistically significant difference between Group 1 and Groups 2, 3, 4, and 5 (p<0.001). Immunohistochemical changes were significantly lower in the control group than in other groups. Moreover, the median value of immunohistochemical changes was lower in Group 4 (1 [0/2]) than in Group 3 (1.64 [1/3]). This difference was statistically significant (p<0.001). Immunohistochemical changes were significantly lower in Group 4 than in Group 3 (Table 2).

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

483

Kardeş et al. Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

Table 2. Statistical comparison of Schwann cell proliferation, axonal degeneration, inflammation, and immunohistochemical changes according to the groups

Schwann C.Proliferation

Axonal Degeneration

Inflammation

Immunohistochemistry

Med. (Min./Max.)

Med. (Min./Max.)

Med. (Min./Max.)

Med. (Min./Max.)

=I

0 (0/0)

0.13 (0/1)

0.06 (0/1)

Group 1

1 (1/1)

Group II

=II

1.08 (0/2)

1.44 (1/2)

0.92 (0/2)

1.57 (0/3)

Group III

=III

1.56 (1/2)

1.07 (0/2)

0.53 (0/2)

1.64 (1/3)

Group IV

=IV

1.07 (0/2)

1.75 (1/2)

0.13 (0/1)

1 (0/2)

Group V

=V

0.86 (0/2)

1.07 (0/2)

0.13 (0/1)

1.38 (0/3)

Total

0.89 (0/2)

1.27 (0/2)

0.34 (0/2)

1.13 (0/3)

<0.001

<0.001

<0.001

<0.001

P-value Binary comparisons

I→II <0.001

0.010 <0.001 <0.001

I→III <0.001

0.641

0.025

<0.001

I→IV <0.001

<0.001

1

0.001

I→V <0.001

0.625

1

<0.001

II→III 0.053

0.036

0.098

0.746

II→IV 0.954

0.067

<0.001

0.056

II→V 0.470

0.042

<0.001

0.566

III→IV 0.060

<0.001

0.025

0.026

III→V 0.008

0.976

0.025

0.369

IV→V 0.435

<0.001

1

0.182

Kruskal–Wallis H Test (Monte Carlo); Post Hoc Test; Dunn’s Test; Med.: Medyan; Min.: Minumum; Max.: Maximum.

DISCUSSION Peripheral nerves can be damaged due to many reasons. These include mechanical factors such as pressure, tension, and violence, as well as thermal, ischemic, radial, electrical, and chemical factors.[8] Peripheral nerve injury, which is currently a major health problem, causes a high rate of disablement and an enormous economic burden.[17] It constitutes an important group of diseases, especially in industrialized countries.[18] More than 350,000 people per year in the United States are exposed to upper extremity injury.[18] Peripheral nerve injury is seen in 2.8%–5% of trauma cases.[18,19] Partial or total motor and sensory loss, loss of autonomic function, and neuropathic pain may develop due to peripheral nerve injury.[20] This can lead to long-term disability and reduce the quality of life and cause material damage.[21] Today, the gold standard treatment for peripheral nerve injury is ETE anastomosis. To provide a tension free primary nerve repair, different techniques can be used, such as re-routing of nerve, mobilization of nerve ends, and bone shortening. This is followed by nerve graft and nerve bridge.[20,22] 484

Therefore, there is a need for developing clinically relevant models to understand the peripheral nerve injury pathophysiology and to evaluate potential treatments.[21] When we examined the literature, various techniques have been proposed to improve the functional outcomes of surgical repair of nerve transection. Nerve and vascular grafts, denatured muscle fibers, and fascial layers are examples of natural tubulization.[23–26] Polyglycolic acid, polyglycan, polyethylene, and silicone were used for synthetic tubulization.

[23,27,28] Yapici et al.[22] reported that vascularized nerve conduit graft showed better regeneration compared to non-vascularized nerve conduit graft but that it cannot be an alternative to autogenous nerve graft.

Dos Reis et al.[29] reported that laser therapy had positive effects on post-anastomotic regeneration of damaged nerves.

Ozbek et al.[30] showed that the use of anastomosis and genistein contributed to nerve healing in experimental sciatic nerve injury.

We also aimed to examine the effects of gabapentin on nerve healing after experimental rat sciatic nerve transection was surgically repaired.

The mechanism of action of gabapentin, which is a lipophilic Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

KardeĹ&#x; et al. Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

GABA analog (an inhibitory neurotransmitter), is still unclear. It is thought that it decreases glutamate-induced cell death in both the central and peripheral nervous system by reducing neuronal cytoplasmic glutamate concentrations in vivo through selective antagonism of an AMPA-type glutamate receptor.[12,15,31] There are many studies showing the neuroprotective effects of gabapentin. Kale et al.[15] reported that gabapentin had a neuroprotective effect in spinal cord ischemia-reperfusion injury in rabbits. Rekling et al.[32] showed that gabapentin had a neuroprotective effect on rat hippocampus.

In our study, Schwann cell proliferation, axonal degeneration, and inflammation were not observed in the control group (Fig. 2). The nerve tissue with prominent Schwann cell proliferation was in Group 3, and the nerve tissue with prominent inflammation in addition to Schwann cell proliferation was in Group 2 (Fig. 2).

There was no statistically significant difference between Group 1 and Groups 4 and 5 in terms of inflammation.

This result proved the strong anti-inflammatory activity of gabapentin. Although not statistically significant, even in the single-dose gabapentin group (Group 3), inflammation was less in Group 2. After 3 and 7 days, it was proven that in-

flammation was at the level of the control group. And these findings were meaningful with the literature.[14,16,30,33,34] In Group 4, significant axonal degeneration was observed (Fig. 2).

In our study, there was a statistically significant difference between the control group (Group 1) and other groups in terms of Schwann cell proliferation. Schwann cell proliferation was significantly lower in the control group. When the relationships between the other groups were evaluated, Schwann cell proliferation was lower in Group 5 than in Group 3.

In an experimental setting, behavior is accepted as motor symptoms of physiopathological processes. Behavioral improvement after peripheral nerve injury is the most important measure of healing for real patients.[18] Functional evaluation is a standard metric for motor function assessment that reflects nerve function after peripheral nerve injury.[30] However, functional evaluation was not performed in our study because nerve regeneration and functional recovery were not completed on the 60th day. This can be investigated by a longterm study; however, it is not possible to evaluate this with the results of this study.[3]

(a)

(b)

(c)

(d)

Figure 2. (a) Control group; Schwann cell proliferation, axonal degeneration, and no inflammation (Group 1) (x10, H&E). (b) Neuronal tissue with prominent Schwann cell proliferation (Group 3) (x20, H&E). (c) Neural tissue showing significant axonal degeneration (Group 4) (x20, H&E). (d) Significant Schwann cell proliferation and inflammation (Group 2) (x20, H&E).

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

485

Kardeş et al. Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

We must travel a considerable distance to achieve the ideal treatment of peripheral nerve injury. The processes of degeneration and regeneration after nerve injury are not fully understood with current information. The clarification of these processes will constitute the basis for progress in the treatment of peripheral nerve injury.[3]

Conclusion The results of our study show that gabapentin can be used as an adjuvant therapy to surgical treatment after peripheral nerve injury. Gabapentin functionally and histopathologically promotes neurological recovery in peripheral nerve injury.

However, the importance of microsurgery experience in treatment should not be forgotten.

Conflict of interest: None declared.

REFERENCES 1. Benli K. Periferik Sinir Cerrahisinin Onemi. Türk Nörosiriirji Dergisi 2005;15:196–7.

2. Akbay A. Periferik Sinirin Mikroanatomisi ve Sinir Kesilerinde Uygulanan Cerrahi Teknikler. Türk Nörosirürji Dergisi 2005;15:198–201.

3. Özer, H. Deneysel Siyatik Sinir Yaralanmasında Poli (3-Hidroksibütirat)(Phb) Vechitosan Kaplı Tübüler Greftler ile Birlikte Mezenşimal Kök Hücre Kullanımının Aksonal rejenerasyona Etkisi. Ankara: Hacettepe Üniversitesi; 2013.

4. Horn KL, Crumley RL. The physiology of nerve injury and repair. Otolaryngol Clin North Am 1984;17:321–33.

5. Brandt KE, Mackinnon S. Microsurgical repair of peripheral nerves and grafts. In: Aston SJ, Beasley RW, Thorne CH, editors. Grabb and Smith‘s Plastic Surgery. 5th. New York: Lippincott Williams & Wilkins; 1997. p.

79–90.

6. Trumble TE, McCallister WV. Repair of peripheral nerve defects in the upper extremity. Hand Clin 2000;16:37–52.

7. Battiston B, Tos P, Conforti LG, Geuna S. Alternative techniques for peripheral nerve repair: conduits and end-to-side neurorrhaphy. Acta Neurochir Suppl 2007;100:43–50.

8. Yüksel TN. Deneysel olarak ratlarda oluşturulan periferik sinir yaralanmalarında telmisartanın rolünün araştırılması. Erzurum: Atatürk Üniversitesi Sağlık Bilimleri Enstitüsü; 2013.

9. Seddon H. Three types of nerve injury. Brain 1943;66:237–88.

10. Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain 1951;74:491–516.

11. Grant, GA Kliot M. In: Winn HR, editor. Youmans neurological surgery.

5th. Saunders; 2004.

12. İstan GK, Erbayraktar Z, Gökmen N, Bağrıyanık A, Kıray M, Erbayraktar SR. Evaluation of Neuroprotective Efficacy of Gabapentin in Experimental Spinal Cord Injury. Sinir Sist Cerrahisi Derg 2015;4:169–84.

13. Kim YK, Leem JG, Sim JY, Jeong SM, Joung KW. The effects of gabapentin pretreatment on brain injury induced by focal cerebral ischemia/reperfusion in the rat. Korean J Anesthesiol 2010;58:184–90.

14. Dougherty JA, Rhoney DH. Gabapentin: a unique anti-epileptic agent.

Neurol Res 2001;23:821–9.

15. Kale A, Börcek AÖ, Emmez H, Yildirim Z, Durdağ E, Lortlar N, et al.

Neuroprotective effects of gabapentin on spinal cord ischemia-reperfusion injury in rabbits. J Neurosurg Spine 2011;15:228–37.

486

16. Taylor CP, Gee NS, Su TZ, Kocsis JD, Welty DF, Brown JP, et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 1998;29:233–49.

17. Sezer A, Guclu B, Kazanci B, Cakir M, Coban MK. Neuroprotective effects of agmatine in experimental peripheral nerve injury in rats: a prospective randomized and placebo-controlled trial. Turk Neurosurg 2014;24:196–201.

18. Kemp SWP, Cederna PS, Midha R. Comparative outcome measures in peripheral regeneration studies. Exp Neurol 2017;287:348–57.

19. Noble J, Munro CA, Prasad VS, Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma 1998;45:116–22.

20. Li R, Wu J, Lin Z, Nangle MR, Li Y, Cai P, et al. Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats. Exp Neurol 2017;288:1–10.

21. Ganguly A, McEwen C, Troy EL, Colburn RW, Caggiano AO, Schallert TJ, et al. Recovery of sensorimotor function following sciatic nerve injury across multiple rat strains. J Neurosci Methods 2017;275:25–32.

22. Yapici AK, Bayram Y, Akgun H, Gumus R, Zor F. The effect of in vivo created vascularized neurotube on peripheric nerve regeneration. Injury 2017;48:1486–91.

23. Cemil B, Ture D, Cevirgen B, Kaymaz F, Kaymaz M. Comparison of collagen biomatrix and omentum effectiveness on peripheral nerve regeneration. Neurosurg Rev 2009;32:355–62.

24. Chiu DT, Janecka I, Krizek TJ, Wolff M, Lovelace RE. Autogenous vein graft as a conduit for nerve regeneration. Surgery 1982;91:226–33.

25. Cruz NI, Debs N, Fiol RE. Evaluation of fibrin glue in rat sciatic nerve repairs. Plast Reconstr Surg 1986;78:369–73.

26. Lundborg G, Hansson HA. Nerve regeneration through preformed pseudosynovial tubes. A preliminary report of a new experimental model for studying the regeneration and reorganization capacity of peripheral nerve tissue. J Hand Surg Am 1980;5:35–8.

27. Meek MF, Dijkstra JR, Den Dunnen WF, Ijkema-Paassen J, Schakenraad JM, Gramsbergen A, et al. Functional assessment of sciatic nerve reconstruction: biodegradable poly (DLLA-epsilon-CL) nerve guides versus autologous nerve grafts. Microsurgery 1999;19:381–8.

28. Valero-Cabré A, Tsironis K, Skouras E, Perego G, Navarro X, Neiss WF. Superior muscle reinnervation after autologous nerve graft or poly-Llactide-epsilon-caprolactone (PLC) tube implantation in comparison to silicone tube repair. J Neurosci Res 2001;63:214–23.

29. dos Reis FA, Belchior AC, de Carvalho Pde T, da Silva BA, Pereira DM, Silva IS, et al. Effect of laser therapy (660 nm) on recovery of the sciatic nerve in rats after injury through neurotmesis followed by epineural anastomosis. Lasers Med Sci 2009;24:741–7.

30. Ozbek Z, Aydin HE, Kocman AE, Ozkara E, Sahin E, Bektur E, et al.

Neuroprotective Effect of Genistein in Peripheral Nerve Injury. Turk Neurosurg 2017;27:816–822.

31. Petroff O, Manor D, Behar K. Gabapentin decreases cortical glutamate rapidly in a rat model. Epilepsy Res 1997.

32. Rekling JC. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation. Neurosci Lett 2003;335:167–70.

33. Emmez H, Yildirim Z, Kale A, Tönge M, Durdağ E, Börcek AO, et al.

Anti-apoptotic and neuroprotective effects of α-lipoic acid on spinal cord ischemia-reperfusion injury in rabbits. Acta Neurochir (Wien) 2010;152:1591–600.

34. Emmez H, Börcek AÖ, Kaymaz M, Kaymaz F, Durdağ E, Civi S, et al.

Neuroprotective effects of gabapentin in experimental spinal cord injury.

World Neurosurg 2010;73:729–34.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Kardeş et al. Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçanlarda deneysel olarak oluşturulan siyatik sinir hasarında gabapentinin primer cerrahi tedaviye etkisi Dr. Özgür Kardeş,1 Dr. Soner Çivi,1 Dr. Erkut Baha Bulduk,2 Dr. Fazilet Kaya Selçuk,3 Dr. Halil İbrahim Süner,1 Dr. Emre Durdağ,1 Dr. Kadir Tufan1 1 2 3

Başkent Üniversitesi Tıp Fakültesi, Adana Dr. Turgut Noyan Uygulama ve Araştırma Merkezi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Adana Eskişehir Devlet Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, Eskişehir Başkent Üniversitesi Tıp Fakültesi, Adana Dr. Turgut Noyan Uygulama ve Araştırma Merkezi, Patoloji Anabilim Dalı, Adana

AMAÇ: Çalışmamızın amacı; sıçanlarda deneysel olarak oluşturulan siyatik sinir yaralanması ve uç-uca anastomoz yapılması modelinde gabapentinin koruyucu etkilerini belirleyerek sinir yaralanmasına bağlı morbiditeyi en aza indirmek ve bu konudaki klinik çalışmalara yön vermektir.

GEREÇ VE YÖNTEM: Çalışmamızda 40 adet yetişkin, erkek, Sprague-Dawley cinsi sıçanlar; rastgele I: Sadece cerrahiye maruz kalan, II: siyatik sinirleri düzgün bir şekilde kesilip tekrar uç-uca anastomoz yapılan ve ek herhangi bir işlem yapılmayan, III: anastomoz yapılıp tek doz 30 mg/kg gabapentin verilen, IV: anastomoz yapılıp üç gün 30 mg/kg gabapentin verilen, V: anastomoz yapılıp yedi gün 30 mg/kg gabapentin verilen olmak üzere beş gruba ayrıldı. Cerrahi işlemden 60 gün sonra yüksek doz tiyopental (50 mg/kg) ile deney sonlandırıldı. Tüm hayvanların sağ siyatik sinirleri alındı ve elde edilen kesitler immünohistopatolojik olarak incelendi.

BULGULAR: İmmünohistokimyasal özellikler ve Schwann hücre proliferasyonu kontrol grubunda, diğer gruplara kıyasla istatistiksel olarak anlamlı daha az oranda saptandı. İkili gruplar arasında ise Grup 3’de 5’e oranla daha fazla hücre proliferasyonu görüldü. Grup 4’deki immünohistokimyasal değişiklikler Grup 3’e göre anlamlı oranda az saptandı. Ayrıca axonal dejenerasyon da Grup 4’de Grup 3’e oranla daha fazla bulundu.

TARTIŞMA: Gabapentin, histopatolojik olarak periferik sinir yaralanmasında nöroprotektif özelliği ile nörolojik düzelmeyi teşvik eder. Çalışmamızın sonuçlarında, gabapentinin, periferik sinir hasarı sonrasında primer cerrahi tedaviye ek tamamlayıcı bir tedavi olarak kullanılabilirliğini göstermektedir.

Anahtar sözcükler: Anastomoz; gabapentin; periferik sinir; siyatik sinir; travma.

Ulus Travma Acil Cerrahi Derg 2018;24(5):481-487

doi: 10.5505/tjtes.2018.66712

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

487

ORIG I N A L A R T IC L E

Risk factors for morbidity in walled-off pancreatic necrosis and performance of continuous postoperative lavage: A single-center experience Mehmet Aziret, M.D.,1 Metin Ercan, M.D.,1 Bilal Toka, M.D.,2 Erkan Parlak, M.D.,2 Kerem Karaman, M.D.1 1

Department of General Surgery, Sakarya University Training and Research Hospital, Sakarya-Turkey

2

Department of Gastroenterology, Sakarya University Training and Research Hospital, Sakarya-Turkey

ABSTRACT BACKGROUND: The aim of this study was to evaluate the risk factors for morbidity in cases of walled-off pancreatic necrosis (WOPN) and the performance of continuous postoperative lavage (CPL) for patients who demonstrated resistance to a minimally invasive approach.

METHODS: The study enrolled 19 of 28 consecutive patients with WOPN who underwent surgical treatment or an endoscopic necrosectomy at Sakarya University Education and Research Hospital. The patients were divided into 2 groups according to the length of time from the first diagnosis of acute pancreatitis (AP) (Group 1, n=19) to preoperation or endoscopic necrosectomy (Group 2) (n=19). All of the cases were retrospectively evaluated and compared in terms of demographic features, operative features, and complications.

RESULTS: No statistically significant difference was found between the number of complications or the duration of hospital stay in terms of age, body mass index, size of the walled-off pancreatic necrosis, American Society of Anesthesiologists score, Ranson’s criteria, operation time, and duration from AP to endoscopic necrosectomy or operation (p>0.05). Performance of an endoscopic necrosectomy was determined to be correlated with a decrease in the number of complications (B=-0.626, 95% confidence interval [CI]: -0.956 to -0.296; p<0.001), and when a high neutrophil-to-lymphocyte ratio (NLR) was detected at first admission, the number of complications was greater (B=0.032, 95% CI: 0.009–0.055; p=0.01). Reproduction in a culture and male gender were found to be risk factors for a prolonged hospital stay (B=0.669, 95% CI: 0.365–0.973; p<0.001), (B=0.484, 95% CI: 0.190–0.778; p=0.003), respectively.

CONCLUSION: CPL is a safe and effective surgical treatment approach for WOPN. Reproduction in a culture, male gender, and a high NLR on first admission and a negative or not-available endoscopic necrosectomy were determined to be risk factors for a poor prognosis.

Keywords: Continuous postoperative lavage; necrosectomy; walled-off pancreatic necrosis.

INTRODUCTION Walled-off pancreatic necrosis (WOPN) is a rare complication associated with acute necrotizing pancreatitis (ANP) and occurs in approximately 5% to 10% of ANP patients.[1,2] WOPN, an encapsulated collection of liquid or solid necrotic tissues that develops more than 4 weeks after the initial ANP,

is associated with high rates of morbidity (40–80%) and mortality (10–28%).[3–5] WOPN can be sterile or infected, solitary or multiple, and tends to be limited to the pancreatic area, but at times, may be located distant from the peripancreatic tissue.[5,6]

Cite this article as: Aziret M, Ercan M, Toka B, Parlak E, Karaman K. Risk factors for morbidity in walled-off pancreatic necrosis and performance of continuous postoperative lavage: A single-center experience. Ulus Travma Acil Cerrahi Derg 2018;24:488-496.

Address for correspondence: Mehmet Aziret, M.D. Adnan Menderes Cad., Sağlık Sok., No: 195, Genel Cerrahi Kliniği, 54100 Sakarya, Turkey Tel: +90 264 - 444 54 00 E-mail: mhmtaziret@gmail.com Ulus Travma Acil Cerrahi Derg 2018;24(5):488-496 DOI: 10.5505/tjtes.2018.84589 Submitted: 15.02.2018 Accepted: 26.07.2018 Online: 17.10.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

488

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage

Endoscopic intervention or surgery is not recommended for asymptomatic, sterile necrosis patients or size of necrosis, site, and dissemination. Minimally invasive interventions, including endoscopic necrosectomy or cystoduodenostomy, transpapillary drainage, percutaneous drainage, and transluminal and percutaneous drainage, can be effective, first-line treatment approaches for the management of WOPN.[7â&#x20AC;&#x201C;10] However, in patients with resistance to such minimal invasive methods, open or laparoscopic surgical methods, including necrosectomy, cholecystectomy, or debridement of pancreatic necrosis, can be performed.[11â&#x20AC;&#x201C;14] In the present study, the aim was to present the risk factors connected with morbidity in cases of WOPN and to evaluate the performance of continuous postoperative lavage (CPL) in patients resistant to a minimally invasive approach.

MATERIALS AND METHODS Patients and Ethics This study was conducted in the surgery department of Sakarya University Education and Research Hospital using records from the period of August 2014 to December 2017.

A total of 19 patients who were treated only for WOPN were eligible for the study. The patients were divided into 2 groups based on the length of time from the initial diagnosis of acute pancreatitis (AP) to surgical operation or endoscopic necrosectomy: the first group (Group 1) included patients who had a diagnosis of AP, and the second group (Group 2) comprised patients who had not yet undergone the surgical operation or endoscopic necrosectomy. All of the cases were retrospectively evaluated in terms of gender and age, body mass index (BMI), co-morbidities, duration from the time of initial diagnosis to operation or endoscopic necrosectomy, alterations in biochemical parameter values from the initial diagnosis to operation or endoscopic necrosectomy, the postoperative length of hospital stay, and postoperative complications. The ethical committee of Sakarya University Education and Research Hospital approved the study protocol.

contrast-enhanced computed tomography (CT) by an experienced radiologist in the hospital (Fig. 1). The 2 groups were compared statistically in terms of gender, age, BMI, co-morbidities, duration from initial diagnosis to operation or endoscopic necrosectomy, alterations in the levels of biochemical parameters from initial diagnosis to operation or endoscopic necrosectomy, the postoperative length of hospital stay, and postoperative complications. The risk factors associated with morbidity were also identified. The patients were followed up at intervals of 1 week, 1 month, and 6 months after being discharged from the hospital.

Inclusion Criteria - Patient must be over 30 years of age, - Patient must have biliary pancreatitis, with a diagnosis of WOPN according to contrast-enhanced CT, - Patient must have normal hemodynamic parameters (PTZ/ INR, aPTZ, etc.).

Exclusion Criteria - Patients younger than 30 years of age, - Patients with malignancy related to the pancreas, distal choledoch, duodenum, periampullary tm etc.), - Patients with non-WOPN disease (pseudocyst, sterile necrosis of pancreas), - Patients with immunosuppression, pregnancy, multiple-organ failure, bile duct injuries during endoscopic retrograde cholangiopancreatography.

Endoscopic Necrosectomy An endoscopic necrosectomy was initiated after premedication with fentanyl and midazolam and a prophylactic intravenous dose of 1 g of ceftriaxone. The endoscopic necrosectomy was performed with a therapeutic duodenoscopy and under fluoroscopy by 2 experienced gastroenterologists.

Methodology A total of 28 patients who had been treated for a pancreatic pseudocyst or WOPN were enrolled in the study. All of the patients had undergone an endoscopic necrosectomy or surgical treatment and were evaluated retrospectively. Patients whose data showed that they still had a pancreatic pseudocyst (n=9) were excluded from the study based on the exclusion criteria. The remaining 19 patients were divided into 2 groups: - Group 1: First diagnosis of AP (AP group) (n=19), and - Group 2: Preoperation or endoscopic necrosectomy group (after >4 weeks) (n=19) Blood samples were taken from all of the patients at the time of first admission for AP and before the operation or endoscopic necrosectomy. WOPN was diagnosed according to Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Figure 1. Walled-off pancreatic necrosis observed with computed tomography (red arrow).

489

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage

(a)

(b)

(c)

(d)

Figure 2. (a-d) Step-by-step endoscopic necrosectomy.

An incision was made with a cystotome from the side where the WOPN wall pressed on the stomach, and then the wall of the WOPN was cannulated with a 0.35-mm guidewire under fluoroscopy. The guidewire position in the WOPN was confirmed with contrast-enhanced fluoroscopy. The cannulated area was first dilated with a 10-F dilatator and then with a 12-mm balloon via guidewire. For those patients with pancreatic debris, a 7-F nasocystic drain was inserted to wash out the debris, and a Nagi stent (Niti-S self-expandable metal stent; TaeWoong Medical, Gyeonggi-do, South Korea)

was inserted for drainage. A nasocystic drain was inserted into the WOPN and then washed with a solution of 20% hydrogen peroxide and 0.9% sodium chloride (NaCl) (150 cc), 3 times daily for a week in the hospital. The stent was removed after a week. Pancreatic debris was removed into the stomach with a 2.5-cm basket (Trapezoid RX; Boston Scientific Corp., Marlborough, MA, USA) and a retriever snare via gastroscopy. A 10-F double pigtail stent (5 to 7 cm) was inserted into the WOPN after the necrotic debris had been cleared in a total of 2 to 5 sequences. The step-by-step procedure is provided in Figure 2. The patients were followed up at 1-month, 3-month, and 6-month intervals. The stents were removed after the sixth month in patients who were asymptomatic and demonstrated a complete recovery.

Four weeks after the removal of the stents, the follow-up was discontinued in patients whose contrast-enhanced CT results showed no necrosis.

Surgical Procedure and Continuous Postoperative Lavage[12]

Figure 3. Open surgery for walled-off pancreatic necrosis.

The surgical procedure was performed in the standard fashion using an open approach with the patient in the supine position. After the administration of anesthesia, the laparotomy was initiated with a midline incision. The gastrocolic ligament was opened using 3/0 silk and an abdominal LigaSure device (Medtronic, Inc., Minneapolis, MN, USA) Debridement of necrotic tissue was carefully performed using hydrogen peroxide and 10% povidine iodine (Figs. 3 and 4). Hemostasis was obtained with bipolar electrocautery and 3/0 propylene sutures. After the necrosectomy, Calotâ&#x20AC;&#x2122;s triangle was anatomically determined before the cystic artery and cystic duct were tied with 3/0 silk and then cut. The gallbladder was dissected away from the liver bed and removed. Hemostasis was obtained with bipolar and monopolar electrocautery.

After achieving hemostasis, a total of 4 drains were inserted sub-hepatically, from the foramen of Winslow to the necrosectomy area (from right of midline, lesser sac), proximal to the spleen, and into the pancreatic area (from left of midline).

The abdomen was typically closed afterwards, but in patients whose abdomen could not be closed due to dilated intestines and edema, Bogotaâ&#x20AC;&#x2122;s bag was used. The patients were then admitted to the intensive care unit. On the postoperative first day, local lavage, gradually increasing from 4 to 10 liters (0.9% NaCl) per 24 hours, was performed continually. Local lavage was administered from the left site drain and removed via the right site drains. The quantity of 0.9% NaCl used

Figure 4. Pancreatic necrosectomy material.

490

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage

was recorded. If the drains were not functional, they were improved manually. The process was continued until serous fluid was observed in the drains. The patients were followed up at 1-week, 1-month, 3- month, and 6-month intervals.

Statistical Analysis The Shapiro-Wilk test was used to determine if the distribution of continuous variables was normal. The Levene test was used to evaluate the homogeneity of variances. Continuous variables were calculated as mean±SD, or median (min-max), as applicable. The number of cases and the percentage were used to describe categorical data.

Table 1. Clinical and operative characteristics and

complications Age (years)

60.9±13.1 (32–81)

Female/male 9/10 Comorbidities, n (%)

15 (78.9)

11 (57.9)

HT

CAP, CHF

5 (26.3)

DM

5 (26.3)

Hypothyroidism

1 (5.3)

Peripheral vascular disease

1 (5.3)

Ranson criteria (first admission), n (%)

The mean differences between groups were compared with Student’s t-test, while the Mann-Whitney U test was applied for comparisons of non-normally distributed data. Categorical variables were evaluated using Fisher’s exact test. Degrees of association between continuous variables were evaluated with Spearman’s rank correlation analysis. To determine whether the differences in biochemical measurements between the preoperative or endoscopic necrosectomy and the diagnosis periods were statistically significant, a paired samples t-test, or Wilcoxon signed-rank test was used, as appropriate.

Multiple linear stepwise regression analyses were used to determine the best predictor(s) of the effect on the number of complications and duration of hospitalization. Any variable with a univariate test with a p value <0.10 was accepted as a candidate for the multivariable model, along with all variables of known clinical importance. The coefficient of regression, 95% confidence interval (CI), and a t-statistic for each independent variable were also calculated. As a result of nonnormal distribution, logarithmic transformation was used for both the number of complications and the duration of hospitalization in regression analyses.

0

5 (26.3)

1

2 (10.5)

2

9 (47.4)

3

Total follow-up (months)

3 (15.8) 19 (4–41)

Duration time from AP to ENS or operation (days)

59 (30–335)

Size (cm)

11.6 (6–25)

Length of the hospital stay (days)

28 (10–82)

Operation time (min) Preoperative ERCP, n (%)

100 (70–180) 9 (47.4)

Preoperative cholelithiasis, n (%)

19 (100.0)

Postoperative ERCP, n (%)

11 (57.9)

Endoscopic necrosectomy, n (%)

8 (42.1)

Surgical methods, n (%)

Cholecystectomy

13 (68.4)

Necrozectomy and/or dedridman

13 (68.4) 10 (52.6)

Bogota bag

Right hemicolectomy and ileostomy

Gastrotomy, choledochotomy,

and T-tube drainage

1 (5.2) 1 (5.2)

The data analysis was performed using SPSS Statistics for Windows, Version 17.0. (SPSS, Inc., Chicago, IL, USA). A p value of less than 0.05 was considered statistically significant.

Number of complications

3 (0–6)

Total complications, n (%)

18 (94.7)

Reproduction of the culture

12 (63.2)

RESULTS

Readmission

11 (57.9)

Pancreas fistula

10 (52.6)

Surgical side infection

9 (47.4)

Of a total of 28 patients, 19 were enrolled in the study, and 9 patients were excluded for failing to meet the inclusion criteria. The mean age of those included in the study was 60.9 years (±13.1; 32–81 years) and the group comprised 9 female and 10 male patients. The mean body mass index (BMI) was 26.2 kg/m2 (±6.7 kg/m2). Most of the patients (78.9%) had comorbidities: the most common were hypertension (57.9%), diabetes mellitus (26.3%), and congestive heart failure, or coronary artery disease (26.3%) (Table 1). Among all of the patients, there were 81.5% cases of abdominal pain, 62.2% cases with a loss of appetite, and 45% cases reporting nausea or vomiting at the first admission to the hospital.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Atelectasis, effusion, and other

4 (21.1)

Reoperation

4 (21.1)

Recurrence

3 (15.7)

AP: Acute pancreatitis; CAP: Coronary artery disease; CHF: Congestive heart failure; DM: Diabetes mellitus; ENR: Endoscopic necrosectomy: HT: Hypertension.

The median follow-up time was 19 months (4–41 months), the median duration from AP diagnosis to endoscopic necrosectomy or operation was 59 days (30–335 days), the me491

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage

Table 2. Alteration in biochemical parameters by group

n

First diagnosis of AP

Preoperative or ENS

p

Range

CA 19-9

8

86 (2–376)

3.9 (2–23)

0.028†

-75 (-369.7–0.1)

Amylase

19

1800 (309–5286)

64.5 (18–292)

<0.001†

-1733 (-5257–-211)

Lipase

16

1225 (23–13395)

33 (8–246)

<0.001†

-1184.5 (-13285–3)

CRP

19

16.6 (0.1–151.0)

107 (3–298)

0.002†

69 (-25.3–171.6)

Glucose

19

155 (110–803)

117 (71–280)

0.006

-27 (-523–67)

AST

19

143 (20–1646)

26 (11–84)

0.005†

-112 (-1626–51)

ALT

19

120 (12v1037)

17 (6–53)

0.002†

-85 (-1015–37)

T. Bilirubin

19

1.43 (0.29–8.75)

0.97 (0.29–14)

0.314†

-0.19 (-5.95–10.00)

D. Bilirubin

19

0.75 (0.05-4.09)

0.27 (0.1–7)

0.235†

-0.29 (-3.08–5.00)

LDH

19

378 (220–1743)

209 (158–497)

<0.001†

-130 (-1585–217)

Albumin

19

3.94±0.33

3.19±0.66

ALP

19

119 (49–242)

91 (3.2–1107)

0.103†

-29 (-204–1013)

GGT

19

189 (9–882)

33 (10–1119)

0.126

-115 (-849–978)

Calcium

19

8.7 (7.3–10.3)

8.5 (4.6–9.7)

0.056†

-0.4 (-3.8–1.0)

Platelet count

19

202 (53.6–658)

249 (117–535)

0.494

7 (-397–481.4)

NLR

19

7.6 (1.7–27.7)

2.5 (1.1–68)

0.061†

-3.1 (-16.8–48.2)

RDW

19

15.4 (13.4–18.9)

16.7 (14.1–19.3)

0.085†

0.8 (-3.9–5.2)

PDW

19

17.7 (13.2–22)

17.5 (16.6–19.6)

0.171†

-0.4 (-2.9–4.8)

†

<0.001 -0.75±0.69 ‡

†

†

Wilcoxon signed-rank test; ‡Paired samples t-test. ALP: Alkaline phosphatase; ALT: Alanine transferase; AP: Acute pancreatitis; AST: Aspartate transferase; CA: Cancer antigen 19-9; CG: Cystogastrostomy; CRP: C-reactive protein; D. Bilirubin: Direct bilirubin; ENS: Endoscopic necrosectomy; GGT: Gamma glutamine transferase; LDH: Lactate dehydrogenase; NLR: Neutrophil-to-lymphocyte ratio; PDW: Platelet distribution width; RDW: Red blood distribution width; T. Bilirubin: Total bilirubin.

†

dian size of the WOPN was 11.6 cm (6–25 cm), and the median length of hospital stay was 28 days (10–82 days).

All 19 (100.0%) of the patients had preoperative/endoscopy cholelithiasis, and 9 (47.4%) had a history of endoscopic retrograde cholangiopancreatography (ERCP). An endoscopic necrosectomy was performed on 8 (42.1%) patients. The median operation time was 100 minutes (70–180 minutes). The surgical methods used were cholecystectomy (68.4%), necrosectomy and/or debridement (68.4%), Bogota bag (52.6%), right hemicolectomy and ileostomy (5.2%), and gastrotomy, choledochotomy, and T-tube drainage (5.2%) (Table 1).

A pancreatic fistulas seen in the patients were a low-impact pancreatic fistula (<20–30 mL drainage), and the clinical course was uneventful with medical treatment. However, the grade B fistulas observed were high-impact pancreatic fistulas (>50–300 mL drainage) and had a symptomatic clinical course (fever, abdominal pain, surgical site infections). A somatostatin analogue was administered to the 3 patients with a grade B pancreatic fistula and total parenteral nutrition was used maintain their nutrition. The pancreatic fistulas were treated for 1 to 3 months with ERCP+ endoscopic sphincterotomy and plastic stents.

There were no cases of mortality in the study. Of the 19 patients, the rate of major complications was 78.9%. The most common complications were reproduction of the culture (63.2%), re-admission (57.9%), pancreatic fistula 10 (52.6%), surgical side infection (47.4%), atelectasia or pleural effusion (21.1%), and (21.1%), recurrence (15.7%). Escherichia coli (21%), Staphylococcus spp. (21%), Candida albicans (15.7%), and Enterococcus faecalis (15.7%) were the most observed growths seen at the surgical site or in the blood or urinary cultures. Those patients who were found to have these infections were referred to the infectious disease clinic and antibiotic treatment was initiated according their anti-biogram.

Among the 19 patients, there were 7 grade A and 3 grade B pancreatic fistulas observed in the present study. The grade

A surgical site infection was observed in a total of 9 (47.4%) patients. A wound culture was taken, prophylactic antibiotics were administered, and surgical site care was provided until complete healing was achieved.

492

The median amylase, lipase, C-reactive protein, cancer antigen 19-9, blood glucose, aspartate transaminase, alanine transaminase, and albumin levels measured at the first admission to the hospital were higher than they were at the time of the preoperative or pre-endoscopic necrosectomy, with a statistically significant difference found between the 2 groups (p<0.05) (Table 2). Table 3 demonstrates the relationship between certain characteristics of the patients, the number of complications, and the duration of hospitalization. When the Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage

Table 3. Comparison of the number of complication and the length of hospital stay in terms of patient characteristics

Number of complications

p †

Length of hospital stay

p†

Gender 0.968 0.095

Male

3 (0–6)

29.5 (22–82)

Female

3 (1–6)

21 (10–40)

Comorbidities

0.736

Yes

3 (0–6)

43.5 (28–82)

No

3 (1–6)

23 (10–49)

Hyperstension

0.968 0.968

No

3 (0–6)

29.5 (10–82)

Yes

3 (1–6)

28 (16–49)

CAD, CHF

0.559

No

3 (0–6)

30.5 (15–82)

Yes

3 (1–4)

23 (10–35)

Diabetes mellitus

0.391

No

3 (0–6)

25.5 (10–82)

Yes

3 (1–6)

31 (23–49)

0.661

No

3 (0–6)

33 (15–82)

Yes

3 (1–6)

23 (10–56)

Postoperative ERCP

0.351

No

3 (1–6)

31.5 (15–82)

Yes

2 (0–6)

28 (10–49)

ASA score ≥3

0.315

No

2 (0–6)

29.5 (15–82)

Yes

3 (1–6)

28 (10–49)

Endoscopic necrosectomy

0.219

0.219

Preoperative ERCP

0.062

0.005

No

3 (1–6)

31 (15–82)

Yes

1 (0–3)

25.5 (10–35)

0.182

0.272

0.604

0.177

Cholelithasis – – No

Yes

0 3 (0–6)

0 28 (10–82)

†Mann-Whitney U test. ASA: American Society of Anesthesiologists; CAD: Coronary artery disease; CHF: Congestive heart failure; ERCP: Endoscopic retrograde cholangiopancreatography.

number of complications and duration of hospital stay were compared in terms of patient age, BMI, size of the WOPN, American Society of Anesthesiologists (ASA) score, Ranson’s criteria, operation time, and the length of time from diagnosis of AP to the endoscopic necrosectomy or operation, no statistically significant difference was observed (p>0.05).

The risk factors related to the number of complications and duration of hospital stay were evaluated using multivariate linear regression analysis. The variables identified as candidate risk factors were included in a univariate linear regression model at p<0.10. Endoscopic necrosectomy and the neutrophil-to-lymphocyte ratio (NLR) at first admission were Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

the most the decisive risk factors for the number of complications. The performance of an endoscopic necrosectomy was correlated with a reduced number of complications in these patients with WOPN (B=-0.626, 95% CI: -0.956 to -0.296; p<0.001). On the other hand, when a high NLR was detected at first admission, the number of complications increased (B=0.032, 95% CI: 0.009–0.055; p=0.01).

Reproduction in a culture and male gender were the most decisive risk factors for length of hospital stay. When the results were positive for reproduction in a culture, the length of the hospital stay increased (B=0.669, 95% CI: 0.365–0.973; p<0.001). Further, the length of hospital stay was longer 493

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage

in males than in females (B=0.484, 95% CI: 0.190–0.778; p=0.003) (Tables 5 and 6).

DISCUSSION The results of this study indicated that endoscopic necrosectomy reduced the number of complications, such as pancreatic fistula, readmission, reproduction in a culture, and Table 4. Comparison between length of hospital stay and complications

n

Length of hospital stay

Pancreatic fistula

p†

0.211

No

9

23 (10–40)

Yes

10

30.5 (19–82)

Surgical site infection

0.133

No

10

22.5 (10–49)

Yes

9

31 (19–82)

Atelectasis, effusion, and other

0.185

No

15

28 (10–56)

Yes

4

35 (23–82)

Reoperation 0.100

No

15

23 (10–56)

Yes

4

33 (30–82)

Readmission 0.310

No

8

29.5 (19–56)

Yes

11

23 (10–82)

Reproduction in culture

0.003

No

7

22 (10–28)

Yes

12

33 (19–82)

Recurrence 0.109

No

16

28 (10–82)

Yes

3

35 (33–56)

Mann-Whitney U test.

†

surgical side infection. Furthermore, CPL of a necrotic area on a daily basis is safe and effective, and reduces mortality when endoscopic necrosectomy cannot be performed or is not available. In the present study, more than two-thirds of the patients were successfully treated with CPL and did not require another major abdominal surgery. The risk factors for prolonged length of hospital stay included patients with reproduction in a culture and male gender (p<0.001, p=0.003, respectively). A high NLR, which is generally seen as a predictive or prognostic factor in acute or chronic diseases, was determined to be a risk factor for complications (p=0.01).

On the other hand, it was found that age, BMI, the size of the WOPN, the ASA score, Ranson’s criteria, operation time, and duration from AP diagnosis to endoscopic necrosectomy or operation were not risk factors for complications or the length of hospital stay (p>0.05).

Recently, minimally invasive interventions, including endoscopic ultrasound-guided transmural drainage, a double pigtail plastic stent (DPS), lumen-apposing metal stents (LAMS), straight biliary fully covered self-expandable metal stents, and percutaneous necrosectomy have been the preferred firstline approaches for the treatment of WOPN due to the lower morbidity rate associated with their use.[8–15] There have been many studies demonstrating the superiority of minimally invasive approaches in terms of effectiveness, safety, and morbidity. Sahar et al.[16] carried out a study comparing the results of DPS and LAMS used with percutaneous drainage in the treatment of WOPN with 25 patients in each group. The outcomes revealed similar technical success (100% vs 100%), time to resolution of WOPN (77 vs 63 days), length of hospital stay (14.5 vs 13.1 days), and adverse effects (24% vs 32%). These results suggested that LAMS do not appear to substantially improve DPS outcomes when combined with percutaneous drainage and they are associated with higher costs; therefore, their use should be discouraged.[16,17] Additionally, in a randomized clinical study comparing endoscopic transgastric necrosectomy and surgical necrosectomy for ANP conducted by Bakker et al.[18] that included 22 patients, the authors found that endoscopic necrosectomy decreased postoperative inflammation as measured by the cytokine in-

Table 5. Risk factors of complications and length of hospitalization

Coefficient of regression

95% Confidence interval Lower limit

t-statistic

p

Upper limit

Number of complications Endoscopic necrosectomy

-0.626

-0.956

-0.296

-4.020

<0.001

Neutrophil-to-lymphocyte ratio (first diagnosis)

0.032

0.009

0.055

2.935

0.010

Length of hospitalization Reproduction in culture

0.669

0.365

0.973

4.660

<0.001

Male gender

0.484

0.190

0.778

3.491

0.003

494

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage

terleukin 6, as well as pancreatic fistula (10% vs 70%), and mortality and major morbidity (20% vs 80%).

A study comparing endoscopic drainage and surgical necrosectomy reported by Rana et al.[19] found that structural and functional impairment of the pancreas was seen less frequently in patients who had endoscopic drainage than in patients who underwent surgery due to the lower rates of diabetes (19.2% vs 44%), pancreatic fluid collection (3.8% vs 20%), and steatorrhea (3.8% vs 8%).

Although endoscopic or percutaneous interventions are related to decreased intervention time, hospital costs, pain, and morbidity, they may not always be possible or performed successfully every time. At Sakarya University Education and Research Hospital, endoscopic treatment approaches are performed by experienced gastroenterologists, but in patients with WOPN who have acute peritonitis or who are resistant to endoscopic intervention, the open surgery approach can be performed safely and effectively. The literature includes studies indicating the effectiveness of open surgery for WOPN. [19,20] In the open abdomen strategy, after necrosectomy and debridement, the abdomen is reopened every 1 to 3 days until all necrosis and/or infected material is removed. In the CPL approach, after necrosectomy and debridement, the abdomen is not reopened, and local lavage, gradually increasing from 4 to 10 liters per 24 hours, is performed continually. In 1988, Beger et al.[12] first described how CPL decreased morbidity and mortality in cases of ANP and demonstrated its excellent results. Of these 2 open surgical approaches, CPL is the most commonly performed worldwide.[20] A systematic review of 16 studies of ANP conducted by Nieuwenhuijs et al.[21] reported the following: mortality (27%), pancreatic fistula (21%), gastrointestinal fistula (20%), colonic necrosis (18%), hemorrhage (21%), incisional hernia (34%), and reoperation (66%). The review also found that the mean length of hospital stay in the intensive care unit (ICU) was 29 days.

Nieuwenhuijs et al.[21] also conducted a review that involved 775 patients with ANP treated with CPL and reported the following: mortality (15%), pancreatic fistula (35%), gastrointestinal fistula (8%), colonic necrosis (2%), and hemorrhage (9%). Additionally, the mean length of hospital stay in the ICU was reported as 24 days.

Endoscopic necrosectomy is an effective first-line treatment approach for WOPN. However, in patients resistant to endoscopic necrosectomy procedures or if endoscopic drainage is unavailable, CPL can be a curative surgical treatment option, based on the results reported in the present study and in the literature. The effectiveness of the present surgical approach is attributed to the continuous washing of the necrotic area with 0.9% NaCl daily. Necrotic tissue debris related to inflammation mediators and cytokines was removed with this continuous lavage technique and ensured that the course of the WOPN treatment could be conducted safely and uneventfully.

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

In the present study, there were no cases of mortality, and the morbidities observed were similar to those reported in the literature. The following rates were found for the variables focused on in this study: reproduction of the culture (63.2%); readmission (57.9%); pancreas fistula (52.6%); surgical side infection (47.4%); atelectasis, effusion, and other (21.1%); reoperation (21.1%); and recurrence (15.7%).

This study’s main limitations are that it was a retrospective study and that the study sample size was too small for a more detailed analysis.

Conclusion CPL is a safe and effective surgical treatment approach for patients resistant to endoscopic necrosectomy procedures or unable to undergo endoscopic drainage in cases of WOPN. Reproduction in a culture, male gender, a high NLR measured at first admission, and negative or unavailable endoscopic necrosectomy are risk factors for poor outcomes.

Conflict of interest: None declared.

REFERENCES 1. Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis.

Am J Gastroenterol 2006;101:2379–400.

2. Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108:1400–15.

3. Trikudanathan G, Attam R, Arain MA, Mallery S, Freeman ML. Endoscopic interventions for necrotizing pancreatitis. Am J Gastroenterol 2014;109:969–81.

4. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102–11.

5. Cheung MT, Li WH, Kwok PC, Hong JK. Surgical management of pancreatic necrosis: towards lesser and later. J Hepatobiliary Pancreat Sci 2010;17:338–44.

6. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 2013;13:e1–15.

7. Andrén-Sandberg A, Dervenis C. Pancreatic pseudocysts in the 21st century. Part I: classification, pathophysiology, anatomic considerations and treatment. JOP 2004;5:8–24.

8. Varadarajulu S, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology 2013;145:583–90.

9. Baron TH, Harewood GC, Morgan DE, Yates MR. Outcome differences after endoscopic drainage of pancreatic necrosis, acute pancreatic pseudocysts, and chronic pancreatic pseudocysts. Gastrointest Endosc 2002;56:7–17.

10. Hookey LC, Debroux S, Delhaye M, Arvanitakis M, Le Moine O, Devière J. Endoscopic drainage of pancreatic-fluid collections in 116 patients: a comparison of etiologies, drainage techniques, and outcomes.

495

Aziret et al. Risk factors for morbidity in WOPN and performance of continuous postoperative lavage Gastrointest Endosc 2006;63:635–43.

11. van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, et al. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med 2010;362:1491–502.

12. Beger HG, Büchler M, Bittner R, Oettinger W, Block S, Nevalainen T. Necrosectomy and postoperative local lavage in patients with necrotizing pancreatitis: results of a prospective clinical trial. World J Surg 1988;12:255–62.

13. Traverso LW, Kozarek RA. Pancreatic necrosectomy: definitions and technique. J Gastrointest Surg 2005;9:436–9.

14. Rau B, Bothe A, Beger HG. Surgical treatment of necrotizing pancreatitis by necrosectomy and closed lavage: changing patient characteristics and outcome in a 19-year, single-center series. Surgery 2005;138:28–39.

15. Yasuda I, Nakashima M, Iwai T, Isayama H, Itoi T, Hisai H, et al. Japanese multicenter experience of endoscopic necrosectomy for infected walled-off pancreatic necrosis: The JENIPaN study. Endoscopy 2013;45:627–34.

16. Sahar N, Kozarek R, Kanji ZS, Ross AS, Gluck M, Gan SI, et al. Do

lumen-apposing metal stents (LAMS) improve treatment outcomes of walled-off pancreatic necrosis over plastic stents using dual-modality drainage? Endosc Int Open 2017;5:E1052–E1059.

17. Vazquez-Sequeiros E. Treatment of walled-off pancreatic necrosis: when and how? Endosc Int Open 2017;5:E1060–E1061.

18. Bakker OJ, van Santvoort HC, van Brunschot S, Geskus RB, Besselink MG, Bollen TL, et al. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA 2012;307:1053–61.

19. Rana SS, Bhasin DK, Rao C, Sharma R, Gupta R. Comparative evaluation of structural and functional changes in pancreas after endoscopic and surgical management of pancreatic necrosis. Ann Gastroenterol 2014;27:162–166.

20. Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch PG, et al. IAP Guidelines for the Surgical Management of Acute Pancreatitis. Pancreatology 2002;2:565–73.

21. Nieuwenhuijs VB, Besselink MG, van Minnen LP, Gooszen HG. Surgical management of acute necrotizing pancreatitis: a 13-year experience and a systematic review. Scand J Gastroenterol Suppl 2003:111–6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Walled-off pankreatik nekrozda morbiditiye etki eden risk faktörleri ve ameliyat sonrası sürekli lavajın etkinliği: Tek merkez deneyimi Dr. Mehmet Aziret,1 Dr. Metin Ercan,1 Dr. Bilal Toka,2 Dr. Erkan Parlak,2 Dr. Kerem Karaman1 1 2

Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Sakarya Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi, Gastroenteroloji Kliniği, Sakarya

AMAÇ: Walled-off pankreatik nekrozda (WOPN) morbiditeye eden risk faktörlerini değerlendirmeyi ve endoskopik nekrozektomiye dirençli hastalarda sürekli ameliyat sonrası lavajın etkilerini ortaya koymayı planladık.

GEREÇ VE YÖNTEM: Bu çalışmaya hastanemizde cerrahi tedavi veya endoskopik nekrozektomi yapılan 28 WOPN’li hastanın 19’u kabul edildi ve hastalar iki gruba ayrıldı; ilk akut pankreatit (AP) tanısı konulduğu zaman (Grup 1, n=19), operasyon veya endoskopik nekrozektomi yapılan zamana kadar (Grup 2, n=19). Hastalar demografik özellikleri, operasyon bulguları ve komplikasyonları açısından karşılaştırıldı.

BULGULAR: Hastalar hastanede kalış süresi ve komplikasyon arasında, yaş, vücut kitle indeksi, WOPN çapı, ASA skoru (American Society of Anesthesiologists), Ranson kriteri, operasyon zamanı, ilk başvuradan operasyon veya endoskopik nekrozektomi yapılan zamana kadar değerlendirildiğinde istatistiksel farklılık yoktu (p>0.05). Endoskopik nekrozektomi yapıldıkça komplikasyon sayısı azalmaktaydı (B=-0.626, %95 CI: -0.956– -0.296 ve p<0.001), ayrıca ilk başvurudaki nötrofil lenfosit oranı (NLR) düzeyi arttıkça komplikasyon sayısı artmaktaydı (B=0.032, %95 CI: 0.009– 0.055 ve p=0.01). Kültürde üreme (B=0.669, %95 CI: 0.365–0.973 ve p<0.001) ve erkek cinsiyet (B=0.484, %95 CI: 0.190–0.778 ve p=0.003) hastanede kalış süresini arttıran risk faktörüydü.

TARTIŞMA: Sürekli ameliyat sonrası lavaj WOPN’de etkili ve güvenli bir cerrahi tedavi yöntemidir. Ayrıca, kültürde üreme, erkek cinsiyet, yüksek NLR düzeyi, yetersiz veya ulaşılamayan endoskopik nekrozektomi kötü prognoza etki eden risk faktörleridir.

Anahtar sözcükler: Nekrozektomi; ameliyat sonrası sürekli lavaj; walled-off pankreatik nekrozis.

Ulus Travma Acil Cerrahi Derg 2018;24(5):488–496

496

doi: 10.5505/tjtes.2018.84589

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

CAS E R EP O RT

Heparin-free veno-venous ECMO applied to a patient with severe lung contusion and hypovolemic shock due to trauma Seong Ho Moon, M.D.,1 Ki Nyun Kim, M.D.,1 Jae Jun Jung, M.D.,1 Jae Hong Park, M.D.,2 Joung Hun Byun, M.D.1 1

Department of Thoracic and Cardiovascular Surgery, Changwon Hospital, Gyeongsang National University College of Medicine,

Republic of Korea, Changwon - South Korea 2

Department of Thoracic and Cardiovascular Surgery, Samsung Changwon Hospital, Sungkyunkwan University College of Medicine,

Gyeongsangnam-do - Korea

ABSTRACT Veno-venous extracorporeal membrane oxygenation (VV-ECMO) plays a crucial role when the lung is extensively damaged and when conventional management has failed. ECMO provides adequate tissue oxygenation and an opportunity for lung recovery. However, ECMO remains contraindicated in patients with a risk of bleeding because of systemic anticoagulation during the treatment. A 26-yearold female experienced polytrauma due to a traffic accident 1 h before arrival. Simple chest radiography and chest computed tomography showed a large right hemopneumothorax with atelectasis of the right lung and severe contusion of the left lung. Heparin-free VV-ECMO was applied peripherally via both femoral veins. Under the ECMO support, right lower lobectomy was successfully performed. Although contraindicated in polytraumatic patients with hemorrhagic shock, surgical repair with the application of ECMO may be feasible if bleeding is well controlled. The patient was discharged without significant complications.

Keywords: Extracorporeal membrane oxygenation; hemorrhagic shock; polytraumatic.

INTRODUCTION Patients with polytrauma reportedly experience associated chest trauma in 50% of cases.[1,2] Life-threatening complications include hemorrhagic shock and severe respiratory failure due to chest trauma.[3] Extracorporeal membrane oxygenation (ECMO) helps maintain systemic tissue oxygenation when pulmonary function is compromised. However, ECMO is contraindicated in some patients, particularly in those where further bleeding may be induced by systemic anticoagulation used during treatment, for example, patients with hemorrhagic polytrauma associated with pulmonary contusion and other organ damage.[4] The application of heparinfree ECMO may be a solution for systemic anticoagulation during treatment. Polytraumatic patients rarely undergo

surgery with the application of ECMO. There are few cases of VV-ECMO application to patients with massive hemothorax due to deep lung lacerations. Here, we report the successful use of ECMO in a 26-year-old female who experienced hypovolemic shock and respiratory failure due to an extensively damaged lung.

CASE REPORT A 26-year-old female experienced polytrauma due to a traffic accident 1 h before arrival. She did not have any known relevant medical history. At the time of arrival at our emergency department, her vital signs were as follows: blood pressure, 70/50 mmHg; heart rate, 120/min; respiratory rate, 25/min; and mental status, semicoma (Glasgow Coma Score: 8). Ar-

Cite this article as: Moon SH, Kim KN, Jung JJ, Park JH, Byun JH. Heparin-free veno-venous ECMO applied to a patient with severe lung contusion and hypovolemic shock due to trauma. Ulus Travma Acil Cerrahi Derg 2018;24:497-500.

Address for correspondence: Joung Hun Byun, M.D. 11, Samjeongja-ro, Seongsan-gu, Changwon-si 51472, Rep. of Korea Changwon, South Korea Tel: 82-55-214-1000 E-mail: jhunikr@naver.com Ulus Travma Acil Cerrahi Derg 2018;24(5):497-500 DOI: 10.5505/tjtes.2018.33802 Submitted: 27.03.2018 Accepted: 27.06.2018 Online: 07.09.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

497

Moon et al. Veno-venous ECMO applied for severe lung contusion with hypovolemic shock

terial blood gas analysis revealed hypoxemia and acidosis with a pH of 7.16, PaO2 of 35 mmHg, PaCO2 of 54 mmHg, and oxygen saturation of 50%. Her hemoglobin level was 10.9 g/dL, and her platelet count was 290,000/ÎźL. She was intubated immediately and was placed on a mechanical ventilator [FiO2, 1.0; positive end expiratory pressure (PEEP), 10 cmH2O; peak inspiratory pressure (PIP), 35 cmH2O]. The pupils were 2 mm in diameter and minimally reactive bilaterally. The left arm had sustained crushing injuries, and ulnar, radius, and humerus fractures were suspected. Blood flow in the left radial artery was identified using Doppler ultrasound.

Breathing sounds were decreased, and a flail chest and severe subcutaneous emphysema of the entire upper body were observed. Chest computed tomography (CT), brain CT, and focused assessment with sonography for trauma were performed at the earliest. There was no intracranial hemorrhage or definitive abdominal organ injury. Simple chest radiography

(a)

and chest CT showed a large right hemopneumothorax with atelectasis of the right lung and severe contusion of the left lung (Figs. 1a, b). A 28-Fr chest tube was inserted in the right pleural cavity, and 3,000 cc of blood was drained for 1 h.

Arterial blood gas analysis after 1 h under the previous mechanical ventilation settings (FiO2, 1.0; PEEP, 10 cmH2O; PIP, 35 cmH2O) showed that pH, PaO2, and PaCO2 were 7.02, 50 mmHg (oxygen saturation, 60%), and 80 mmHg, respectively.

Massive transfusion [packed red blood cells (PRBCs), 8 U; fresh frozen plasma (FFP), 5 U] was given via a pressure infusion system (Auto PC Automatic Pressure Infuser, Acemedical), and right exploratory thoracotomy was performed. Because hypoxia (oxygen saturation, 70%) was persistent during anesthesia, heparin-free VV-ECMO (3.0 L/min; MAQUET Cardiopulmonary AG, Hirrlingen, Germany) was applied peripherally via both femoral veins using a DLP-21, 22-Fr venous cannula (Medtronic Inc., Minneapolis, MN, USA). Under the

(b)

Figure 1. Simple chest radiography (a) and chest computed tomography (b) show a large right hemopneumothorax and severe contusion of the left lung.

(a)

(b)

(c)

Figure 2. Immediate postoperative simple chest radiography shows venous catheters (black arrow) for extracorporeal membrane oxygenation (a). Simple chest radiography shows improvement on postoperative day 4 (b) and at the time of patient discharge (c).

498

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Moon et al. Veno-venous ECMO applied for severe lung contusion with hypovolemic shock

ECMO support, the oxygen saturation level was maintained at 95% during surgery.

organs, careful consideration of ECMO is needed to account for possible hemorrhage control.

Right lower lobe lobectomy was performed because of a deep laceration of approximately 8 cm and severe lung contusion on the right lower lobe. PRBCs (8 U) and platelet concentrate (8 U) were transfused during surgery. Fasciotomy was performed due to left forearm compartment syndrome.

Figure 2a shows immediate postoperative simple chest radiography. The amount of hemothorax in the left pleural cavity was increased, and two 6-Fr pigtail catheters were placed under sonography guidance; 400 cc of blood was drained for 1 h via two left pigtail catheters, and no more subsequent draining was performed.

Our patient underwent right chest tube insertion with massive hemothorax (3.000 mL/h), and the hypovolemic shock was not corrected, despite substantial blood transfusion.

Hypoxemia was not corrected with full mechanical ventilation due to severe injury of both lungs. Because hypovolemic shock and multiple organ damage continued, we decided on an emergency operation; however, several complications developed. First, conventional exploratory thoracotomy requires a lateral decubitus position. Hypoxemia was problematic due to severe lung contusion and blood aspiration to the contralateral lung. Second, a severely injured lung is vulnerable to acute respiratory distress syndrome and acute lung failure during massive fluid or blood product infusion. Third, hypothermia and acidosis due to massive transfusion may occur. Based on these potential complications, we decided to apply heparin-free VV-ECMO to the patient.

There was no definitive postoperative bleeding, and 1 U of PRBCs was transfused. ECMO (3.4 L/min) with a mechanical ventilator (FiO2: 0.6, PEEP: 7 cmH2O, PIP: 25 cmH2O) was applied for 4 days. FuthanR (nafamostat mesilate) was used postoperatively for 2 days to control the activating clotting time at 150 s. Simple chest radiography showed improvement at postoperative day 4 (Fig. 2b), and ECMO weaning was initiated. There were no ECMO-related complications during the course. Mechanical ventilator weaning was initiated on postoperative day 8. On postoperative days 19 and 36, internal fixation for the left forearm fracture was performed and a left forearm skin graft was applied, respectively. At discharge, an improvement in simple chest radiography without operative wound complications was seen (Fig. 2c).

DISCUSSION Severe trauma causes approximately 5 million global deaths annually.[3,5] Many patients respond well to trauma-care specialist treatments, including fluid resuscitation, mechanical ventilation, and other invasive procedures. However, patients with concurrent severe chest trauma and hemorrhagic shock have poor prognosis. The significant treatment goals for patients with severe chest trauma and hemorrhagic shock are restoration of blood coagulation by appropriate transfusion (PRBC, platelet, and FFP), surgical repair of bleeding focus, and maintenance of body temperature. The potential survival benefit of ECMO applied to patients with severe lung injury has recently been reported.[6,7] We believe that if there is no hemorrhage of organs other than contused lungs, the application of ECMO will likely have a low risk of additional hemorrhage. However, if there is hemorrhage in other organs, the application of ECMO should be cautiously considered depending on whether any additional hemorrhage can be controlled. In such cases, heparin-free ECMO should be considered. Similarly, if there is a pulmonary hemorrhage, regardless of a hemorrhage in other

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5

Our goals included restoring oxygen, maintaining normothermia, and securing massive transfusion and lung protective ventilation during the operation. Damage control focused on bleeding, and stable vital signs were maintained. Matthias et al. reported that the use of a heparin-free ECMO is beneficial for the survival of polytraumatic patients with pulmonary failure and hemorrhagic shock.[3] In conclusion, although contraindicated in polytraumatic patients with hemorrhagic shock, surgical repair with the application of ECMO may be feasible if bleeding is well controlled.

Conflict of interest: None declared.

REFERENCES 1. Ried M, Bein T, Philipp A, Müller T, Graf B, Schmid C, et al. Extracorporeal lung support in trauma patients with severe chest injury and acute lung failure: a 10-year institutional experience. Crit Care 2013;17:R110.

2. Vecsei V, Arbes S, Aldrian S, Nau T. Chest injuries in polytrauma. Eur J Trauma 2005;31:239–43.

3. Arlt M, Philipp A, Voelkel S, Rupprecht L, Mueller T, Hilker M, et al.

Extracorporeal membrane oxygenation in severe trauma patients with bleeding shock. Resuscitation 2010;81:804–9.

4. Wen PH, Chan WH, Chen YC, Chen YL, Chan CP, Lin PY. Non-heparinized ECMO serves a rescue method in a multitrauma patient combining pulmonary contusion and nonoperative internal bleeding: a case report and literature review. World J of Emerg Surg 2015;10:15.

5. Rossaint R, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, Gordini G, et al. Key issues in advanced bleeding care in trauma. Shock 2006;26:322–31.

6. Cordell-Smith JA, Roberts N, Peek GJ, Firmin RK. Traumatic lung injury treated by extracorporeal membrane oxygenation (ECMO). Injury 2006;37:29–32.

7. Madershahian N, Wittwer T, Strauch J, Franke UF, Wippermann J, Kaluza M, et al. Application of ECMO in multitrauma patients with ARDS as rescue therapy. J Card Surg 2007;22:180–4.

499

Moon et al. Veno-venous ECMO applied for severe lung contusion with hypovolemic shock

OLGU SUNUMU - ÖZET

Travmaya bağlı ciddi akciğer kontüzyonu ve hipovolemik şoku olan bir hastaya heparin verilmeden uygulanan veno-venöz ECMO Dr. Seong Ho Moon, Dr. Ki Nyun Kim, Dr. Jae Jun Jung, Dr. Jae Hong Park, Dr. Joung Hun Byun 1 2

Gangwongsang Ulusal Üniversitesi Tıp Fakültesi, Göğüs ve Kalp Damar Cerrahisi Bölümü, Changwon Hastanesi, Changwon, Güney Kore Sungkyunkwan Üniversitesi Tıp Fakültesi, Göğüs ve Kalp-Damar Cerrahisi Bölümü, Samsung Changwon Hastanesi, Gyeongsangnam-do, Güney Kore

Akciğer aşırı derecede hasarlandığında ve konvansiyonel tedavi başarısız olduğunda venovenöz ekstrakorporeal membran oksijenizasyonu (VVECMO) kritik rol oynar. ECMO dokunun yeterince oksijenlenmesine ve akciğerin toparlanmasına olanak sağlar. Tedavi sırasında sistemik antikoagülasyon uygulandığından kanama riski olan hastalarda ECMO kontrendike olmayı sürdürmektedir. Yirmi altı yaşında kadın hasta gelmeden bir saat önce trafik kazası nedeniyle politravma geçirmiş. Basit torasik radyografi ve bilgisayarlı tomografi sağ akciğer atelektazisiyle birlikte geniş bir sağ hemopnömotoraks ve sağ akciğerde ciddi kontüzyonun varlığını gösterdi. ECMO desteği altında başarıyla sağ alt lob çıkartıldı. Hemorajik şoklu politravma hastalarında kontrendike olmasına rağmen kanama iyice kontrol altına alınmışsa ECMO uygulaması mümkün olabilir. Hasta önemli bir komplikasyon olmaksızın taburcu edilmiştir.

Anahtar sözcükler: Ekstrakorporeal membran oksijenizasyonu; hemorajik şok; politravmatik.

Ulus Travma Acil Cerrahi Derg 2018;24(5):497-500

500

doi: 10.5505/tjtes.2018.33802

Ulus Travma Acil Cerrahi Derg, September 2018, Vol. 24, No. 5