TJTES 2016 / 4 by KAREPUBLISHING

ISSN 1306 - 696X

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

Volume 22 | Number 4 | July 2016

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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 Gürhan Çelik Osman Şimşek Orhan Alimoğlu

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) Amblem Correspondence address (Yazışma adresi) Tel Fax (Faks)

Kaya Sarıbeyoğlu Kaya Sarıbeyoğlu M. Mahir Özmen 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): Merve Şenol • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): June (Haziran) 2016 • 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

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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 2008 in Index Copernicus. Our impact factor in SCI-E indexed journals is 0.5. 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 may be submitted in Turkish or 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, 2001 yılından itibaren Index Medicus ve Medline’da, 2005 yılından itibaren Excerpta Medica / EMBASE indekslerinde, 2007 yılından itibaren Science Citation Index-Expanded (SCI-E) ile Journal Citation Reports / Science Edition uluslararası indekslerinde ve 2008 yılından itibaren Index Copernicus indeksinde yer almaktadır. 2015 yılında SCI-E kapsamında İmpakt faktörümüz 0,5 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 Türkçe ve İngilizce yazılmış makaleler yayınlanabilir. 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 kişiler-

den 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 22

Number - Sayı 4 July - Temmuz 2016

Contents - İçindekiler Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 305-314 Effects of acetaminophen and mannitol on crush injuries in rats: An experimental study Ezilme yaralanması oluşturulan sıçanlarda asetaminofen ve mannitolun etkileri: Deneysel çalışma Çelikmen MF, Sarıkaya S, Özüçelik DN, Sever MŞ, Açıksarı K, Maktav Çelikmen D, Yazıcıoğlu M, Kandemir A, Doğan H, Ayvacı BM, Özaşır Abuşka D, Sadıllıoğlu S 315-321 Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model Deneysel sepsis modelinde melatoninin sitokin salınımı ve kolonik anastomoz iyileşmesi üzerine etkileri Ersoy ÖF, Özkan N, Özsoy Z, Kayaoğlu HA, Yenidoğan E, Çelik A, Özuğurlu AF, Arabacı Çakır E, Lortlar N 322-327 Endogenous erythropoietin level and effects of exogenous erythropoietin in a rat model of blunt chest trauma-induced pulmonary contusion Künt göğüs travmasıyla oluşturulan pulmoner kontüzyon sıçan modelinde eritropoietin düzeyleri ve eksojen eritropoietinin etkileri Bakan V, Kurutaş EB, Çıralık H, Gül M, Çelik A

Original Articles - Orijinal Çalışma 328-332 Comparing Pediatric Trauma, Glasgow Coma Scale and Injury Severity scores for mortality prediction in traumatic children Travma geçirmiş çocuklarda mortalite öngörüsünde Pediyatrik Travma, Glasgow Koma Ölçeği ve Comparing Pediatric Trauma, Travma Şiddet Derecesi skorlarının karşılaştırması Yousefzadeh-Chabok S, Kazemnejad-Leili E, Kouchakinejad-Eramsadati L, Hosseinpour M, Ranjbar F, Malekpouri R, Mohtasham-Amiri Z 333-337 Evaluation of patients with snakebite who presented to the emergency department: 132 cases Acil servise başvuran yılan ısırması olgularının değerlendirilmesi: 132 olgu Şahan M, Taşın V, Karakuş A, Özcan O, Eryiğit U, Kuvandık G 338-343 Role of endothelial nitric oxide synthases system on acute appendicitis Akut apandisitte endotelial nitrik oksit sentaz sisteminin rolü Taşlıdere B, Şener EF, Taşlıdere E, Ekici Günay N, Bol O, Bülbül E, Aktaş RS, Günay N 344-349 Diagnostic utility of the neutrophil-lymphocyte ratio in patients with acute mesenteric ischemia: A retrospective cohort study Akut mezenterik iskemili hastalarda nötrofil-lenfosit oranının tanısal yararı: Geriye dönük kohort çalışma Tanrıkulu Y, Şen Tanrıkulu C, Sabuncuoğlu MZ, Temiz A, Köktürk F, Yalçın B 350-354 Medial mini-open versus percutaneous pin fixation for type III supracondylar fractures in children Çocuk tip III suprakondiler humerus kırıklarında medial mini açık teknikle perkütan tekniğin karşılaştırlması Erçin E, Bilgili MG, Baca E, Başaran SH, Bayrak A, Kural C, Avkan MC 355-360 Is the presence of linear fracture a predictor of delayed posterior fossa epidural hematoma? Lineer kırık varlığı, geç gelişen posterior fossa epidural hematomu açısından bir risk faktörümüdür? Kırcelli A, Özel Ö, Can H, Sarı R, Cansever T, Elmacı İ

Ulus Travma Acil Cerrahi Derg, May 2016, Vol. 22, No. 4

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 22

Number - Sayı 4 July - Temmuz 2016

Contents - İçindekiler

361-364 Implementation of the Ottawa ankle rules by general practitioners in the emergency department of a Turkish district hospital Ottawa ayakbileği kurallarının ülkemizde devlet hastanesi acil servisinde görevli pratisyen hekimler tarafınca kullanımı Daş M, Temiz A, Çevik Y 365-373 Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi Evaluation of medical malpractice in emergency and elective general surgery cases resulting in death Üzün İ, Özdemir E, Esen Melez İ, Melez DO, Akçakaya A 374-378 Çocuklarda vasküler olmayan dördüncü derece böbrek yaralanmalarında minimal invaziv tedavi yaklaşımları Minimally invasive theurapeutic approaches in pediatric nonvascular fourth-grade renal trauma Uçan AB, Günyüz Temir Z, Şencan A, Karkıner A, Evciler H 379-385 Proksimal humerus çok parçalı kırıklarında plak osteosentez ve hemiartroplasti sonuçlarının orta dönem takip ile değerlendirilmesi Mid-term follow-up evaluation of plate osteosynthesis and hemiarthroplasty results in multipart fractures of the proximal humerus Çelik C, Gümüştaş SA, Çeçen GS, Bulut G, Bekler Hİ 386-390 Erişkin humerus alt uç eklem içi parçalı kırıklarda 90° ve 180° plak uygulamalarının karşılaştırılması ve klinik sonuçlar üzerine etkisi Comparison of 90° and 180° plate constructions for comminuted distal humerus fractures in adults, and effects on clinical results Eryuva V, Altay T, Kayalı C, Kement Z, Çıtak C

Case Reports - Olgu Sunumu 391-394 Acute abdomen caused by greater omentum torsion: A case report and review of the literature Omentum majus torsiyonunun neden olduğu akut batın: Olgu raporu ve literatürün gözden geçirilmesi Cremonini C, Bertolucci A, Tartaglia D, Menonna F, Galatioto C, Chiarugi M 395-398 Embolism of a pellet after shotgun injury: From liver to right ventricle Ateşli silah yaralanması sonrası saçma embolisi: Karaciğerden sağ ventrikül Bakan S, Korkmazer B, Baş A, Şimşek O, Barman HA, Çebi Olgun D 399-401 A swallowed metal nail entrapped in the right psoas muscle Sağ psoas kasına saplanan yutulmuş çivi Yıldız İ, Koca YS, Barut İ 402-404 Pencil in the pharynx: Case report of a penetrating foreign body Farinkste kalem: Delici bir yaralanmanın olgu sunumu Kara İ, Ulutabanca H, Kökoğlu K, Güneş MS, Çağlı S

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EXPERIMENTAL STUDY

Effects of acetaminophen and mannitol on crush injuries in rats: An experimental study Mustafa Ferudun Çelikmen, M.D.,1 Sezgin Sarıkaya, M.D.,1 Doğaç Niyazi Özüçelik, M.D.,2 Mehmet Şükrü Sever, M.D.,3 Kurtuluş Açıksarı, M.D.,4 Deniz Maktav Çelikmen, M.D.,5 Mustafa Yazıcıoğlu, M.D.,6 Ali Kandemir, M.D.,1 Halil Doğan, M.D.,6 Barış Murat Ayvacı, M.D.,7 Derya Özaşır Abuşka, M.D.,8 Sıla Sadıllıoğlu, M.D.9 1

Department of Emergency, Yeditepe University Faculty of Medicine, İstanbul-Turkey

İstanbul University Health Sciences Faculty, İstanbul-Turkey

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

Department of Emergency Medicine, İstanbul Medeniyet University Faculty of Medicine, İstanbul-Turkey

Department of Internal Medicine, Haydarpaşa Numune Training and Research Hospital, İstanbul-Turkey

Department of Emergency, Bakırköy Dr. Kadi Konuk Training and Research Hospital, İstanbul-Turkey

Department of Emergency, Okmeydanı Training and Research Hospital, İstanbul-Turkey

Department of Emergency, Haseki Training and Research Hospital, İstanbul-Turkey

Department of Emergency, İstanbul Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The present objective was to evaluate effects of acetaminophen and mannitol on renal function and histopathology in crush injuries. METHODS: Thirty-six rats weighing 370–400 g each were used. No surgery was performed on the first (control) group. The gastrocnemius muscle regions of each rat in the remaining 5 groups were compressed for 2 or 24 hours. In the 4th group, 100 mg/ kg acetaminophen was intraperitoneally administered. In the 5th group, 1 g/kg mannitol was administered. In the 6th group, 100 mg/kg acetaminophen and 1 g/kg mannitol were administered. RESULTS: No statistically significant differences were observed among the treatment groups in terms of sodium, potassium, alanine aminotransferase (ALT), and average creatinine clearance values. Hydropic degeneration, tubular necrosis, presence of immunoperoxidase and myoglobin, tubulus epithelial cell degeneration, and presence of PAS-dyed material in tubular lumen was more prominently decreased in the acetaminophen group than the mannitol group. Improvement was observed in the group that was administered both drugs, compared to the mannitol-only group, though findings were still worse than those of the group administered acetaminophen only. CONCLUSION: In crush injuries, acetaminophen improves histopathological renal damage better than mannitol. When used in conjunction with mannitol, the toxic effect of acetaminophen on the liver is decreased. Keywords: Acetaminophen; crush injury; earthquake; experimental work; mannitol; renal damage.

Address for correspondence: Doğaç Niyazi Özüçelik, M.D. Demirkapı Cad., Karabal Sok., Bakırköy Ruh ve Sinir Hastalıkları Hastanesi Bahçesi İçi, 34740 Bakırköy, İstanbul, Turkey Tel: +90 212 - 414 71 02 E-mail: dogacniyazi@gmail.com Qucik Response Code

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INTRODUCTION Crush syndrome is the second most common cause of death in immediate survivors of earthquakes.[1] In major earthquakes, up to 20% of deaths occur shortly after extrication. [2] Causes of mortality in crush syndrome include hypovolemic shock, hyperkalemia, hypocalcemia, metabolic acidosis, acute tubular necrosis, and acute myoglobinuric renal failure. [3–5] Serum potassium, creatinine, and creatinine kinase levels are important parameters, determining crush syndrome severity.[6] 305

Çelikmen et al. Effects of acetaminophen and mannitol on crush injuries in rats

After the Kobe earthquake, the mortality rate of patients hospitalized early with crush syndrome was 13.4%, while the same rate for traumas other than crush damage was 5.5%.[10] After the Marmara earthquake, acute renal problems due to crush injury were observed in 639 of 5302 patients hospitalized with crush syndrome at 35 centers.[7]

mannitol, and acetaminophen-mannitol combination in the prevention of rhabdomyolysis, acute renal damage, and other fatal complications in rats with induced crush injuries.

In many crush casualties, acute kidney injuries can be prevented by appropriate early fluid resuscitation.[8,9] Fundamental targets in crush syndrome management are early aggressive hydration, urine alkalinization, and mannitol treatment. [10–12] Administration of continuous fluids to victims as soon as possible following extrication helps prevent crush-related acute kidney injuries. Preferred fluid is isotonic saline for reasons of efficacy and availability.[1,11,13] Sodium bicarbonate, added to half-isotonic solutions, may be effective for alkalizing urine in order to prevent tubular deposition of myoglobin and uric acid, to correct metabolic acidosis, and to reduce hyperkalemia.[11,12] Mannitol may be useful in the expansion of extracellular volume, as well as increasing urine output, and preventing renal tubular cast deposition.[14] However, severe side effects have been associated, including congestive heart failure in the event of overdose, as well as potential nephrotoxicity.[15,16]

The present experimental study was conducted at the Experimental Medicine and Research Center of the Yeditepe University Faculty of Medicine. Approval was obtained from the local ethics committee, that of the Yeditepe University for Animal Studies (issue: 151; decision number: 02.12.2010).

MATERIALS AND METHODS Study Design and Settings

Closed-Piston Model Closed-piston model was utilized by means of 2 metal crushing devices previously described in the literature.[20,21] The device (longitudinal axis: 15 cm; horizontal axis: 11 cm) had a maximum piston-effective pressure of 80 pounds (~36 kg) when tightened with a screw system. The crushing procedure was performed on 2 gastrocnemius muscles simultaneously by application of pressure of 40 pounds (~18 kg) from the 2 1-cm circular components at the end of the screw (Fig. 1).

Experiment Animals The present study included 36 Sprague-Dawley rats weighing 370–400 g each. For 7 days prior to initiation of the study, the animals were kept in metal cages in an environment controlled at 22°C, with a 12-hour light/dark cycle. In order to assess the effectiveness of the mechanical crush, a pilot study was performed on 2 rats. The remaining 36 rats were separated into groups of 6 rats each.

New treatment protocols for preventing fatal organ damage, including acute renal failure, in cases of crush syndrome are being investigated. Results of in-vitro and in-vivo studies have shown that acetaminophen decreases the possibility of the ferryl heme transforming into ferric form, induces lipid peroxidation of hemoproteins, and promotes the formation of globin radicals.[17–19] Cytoprotective effects of acetaminophen against organ damage in rats have been observed.[18] In addition, acetaminophen is inexpensive, easily available, and suitable for use in all populations, including pregnant women.

Pilot Study A pilot mechanical crushing procedure was performed on 2 rats in order to ensure that it could be performed effectively, similar to the rodent model of Kirsten Speck et al.[22] After

The present aim was to compare effects of acetaminophen,

(a)

(b)

Figure 1. (a) Pressure continuity of crushing device in equivalent intervals at 40 lbs (~18 kg) by Biopac MP 35 device (BIOPAC Systems, Inc., Goleta, CA, USA). (b) In order to prevent slippage of the crushing device piston, as well as skin maceration, the gastrocnemius regions were wrapped loosely with 1 fold of 5-cm plaster without harming circulation, creating a surface area.

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the rats had undergone the 2-hour procedure under anesthesia and no mobility limitations were observed, the study was modified to include compression of both of the lower-extremity gastrocnemius muscles, dissimilar to previous studies.[22–24]

Anesthesia All rats received 40 mg/kg zolazepam hydrogen chloride (Zoletil 50 flakon; Tum İlaç San., İstanbul, Turkey) and 10 mg/kg xylazine (Rompun flakon; Bayer AG, Leverkusen, Germany) during compression and during surgery. Anesthesia was intramuscularly administered in the right leg.

Crush Method With the exception of the control group, the rats received simultaneous and stable 40-lb (~18 kg) pressure on both gastrocnemius regions for 2 hours under general anesthesia. To prevent slippage of the crushing device piston and skin maceration, the regions were wrapped loosely with 1 fold of 5-cm plaster (Hypafix; BSN Medical GmbH, Hamburg, Germany) without inhibiting circulation, creating a surface area.[25–27] Following application of compression, all rats were placed in metabolic cages, in an environment with a 12-hour light/ dark cycle, temperature of 24°C, and free access to water. All were able to utilize the lower extremities when the effects of anesthesia diminished.

Experimental Groups Group 1: (Control group; n=6): No compression was applied. Group 2: (2-hour compression group; n=6). 40 lbs (~18kg)/ cm2 pressure was applied for 2 hours to both gastrocnemius regions of each rat. Group 3: (24-hour compression group; n=6). 40 lbs (~18kg)/ cm2 pressure was applied for 24 hours to both gastrocnemius regions of each rat.

following the 2-hour period of compression. Urine samples of the other groups were obtained at 24 hours and stored at 4°C.

Biochemical Examination of the Samples Under sterile conditions, cardiac puncture was performed for biochemical analysis, and 4–5 mL blood samples were obtained. Samples were centrifuged for 10 minutes and 3000 spins at 4°C. They were stored at -20°C in the Yeditepe University Medical School Biochemistry laboratory. Sodium, potassium, alanine aminotransferase (ALT), urine, and serum creatinine measurements were performed with use of relevant kits in a Cobas Integra 400 plus autoanalyzer (Roche Diagnostics International AG, Rotkreuz, Switzerland). As serum myoglobin is cleaned from plasma in 6 hours, and the majority of samples were gathered after 24 hours, myoglobin was not included in biochemical sample evaluation. Myoglobin evaluation was scored as histopathological.[17]

Collection of Histological Samples Samples were obtained in an identical manner, performed on an operation table under general anesthesia. Twenty-four hours after initial surgery, the surgical area was cleansed with 10% povidone–iodine, and the abdomen was cut with a 2-cm midline incision starting at 1 cm below the xiphoid process. Upon accessing the retroperitoneum, bilateral nephrectomy was performed for pathological study. Left and right kidneys were halved with a lancet through the long axis, and cubic sections 1x1x0.5 cm in depth were obtained from both lower extremity gastrocnemius muscles. Two muscle cuts from each rat were prepared in the coronal and axial plan. The sections were placed in 10% formaldehyde for histopathological evaluation. Each sampling surgery was completed in nearly 10 minutes.

Histopathological Examination

Group 6: (Acetaminophen + mannitol group; n=6). Immediately following removal of compression, which had lasted 2 hours, doses of acetaminophen and mannitol identical to those of Groups 5 and 6, were consecutively and intraperitoneally administered.

Kidney and muscle samples used for histopathological study were fixed in 10% formaldehyde solution for 24 hours and tracked routinely by sampling at 0.5-cm thickness in the Yeditepe University Medical School Pathology Department. Tissue samples were embedded in paraffin blocks, and cuts of 5-μm thicknesses were prepared. Samples were dyed with hematoxylin-eosin and examined under light microscope. In each preparation, kidney damage was assessed in 10 randomized areas. Hydropic degeneration in the proximal tubules, and inflammation and necrosis in the tubule were scored semiquantitatively, with 0 points signifying no change, 1 point signifying change of less than 25% (mild), 2 points signifying change of 25–50% (mid-range), 3 points signifying change of 50–75% (extreme), and 4 points signifying change of 75% (very extreme).

Urine Examination of Samples

Immunohistochemical Examination

The urine samples of (untreated) Group 2 rats were obtained

Following histopathological examination, myoglobin antibody

Group 4: (Acetaminophen group; n=6). Immediately following removal of compression, which had lasted 2 hours, 100 mg/kg acetaminophen, titrated with distilled water in a 1:10 solution, was intraperitoneally administered at 4 mL/400 g. Group 5: (Mannitol group; n=6). Immediately following removal of compression, which had lasted 2 hours, 1 g/kg mannitol 20% solution was intraperitoneally administered at 2 mL/400 g.

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(species reactivity: human, mouse, rat; -100 Amb) dyeing was performed immunohistochemically on the cuts using the avidin-biotin-peroxidase method. The 5-μm cuts were deparaffinized and rehydrated. In order to prevent endogenous peroxidase activity, they were kept in 3% peroxide for 5 minutes before being cleansed in distilled water. The cuts were then stored in citrate buffer solution at pH 6 (650 microwave) for 5 minutes and kept in Tris buffer solution for 5 minutes. The primary antibody was kept in a humid environment at 28 ºC for 30 minutes. Biotin-marked secondary antibody was administered for 15 minutes, was placed in streptavidin peroxidase conjugate for 10 minutes, then in 3-amino-9-ethylcarbazole (AEC) chromogen for 15 minutes. Every level was washed. Mayer’s hematoxylin was used as background counter dye and closed with a special closing material before being prepared for microscopic examination.

comparison test was used to compare subgroups; chi-square test was used to compare qualitative data, and p<0.05 was considered significant.

RESULTS Laboratory results are shown in Table 1. Average creatinine value closest to that of the control group was observed in the 2-hour compression group. Lowest mean creatinine value among the treatment groups was observed in the acetaminophen group (0.83±0.7 mg/dL), while the highest creatinine level was observed in the mannitol group (1.21±1.75 mg/dL; p=0.177). Mean creatinine clearance value closest to that of the control group was observed in the acetaminophen group (1.35±0.48 mL/min), which also had the highest mean creatinine clearance value. Among the treatment groups, the lowest mean creatinine clearance value was observed in group that had been administered both acetaminophen and mannitol (0.63±0.4 mL/min; p=0.001).

Semiquantitative scoring was performed according to myoglobin dying properties in arteries, in the proximal tubule, distal tubule, in glomeruli and collecting channels, as well as in 10 areas at 40-mm objective. Points were assigned based on the following criteria: 0 point: no change; 1 point: change of less than 25% (mild); 2 points: 25–60% change (mid-range); 3 points: change of 60% and greater (extreme).

While creatinine clearance was found to be significantly different between the control and treatment groups (p<0.05), no statistically significant difference was observed between the groups that had been administered either acetaminophen or mannitol, a finding determined using Dunn’s multiple comparison test (p>0.05).

Statistical Methods Statistical analyses were performed using NCSS statistical software (NCSS LLC, East Kaysville, UT, USA; 2007). Descriptive statistical methods (average, SD, median, interquartile range) were applied, as were tests, including KruskalWallis, to determine intergroup comparison. Dunn’s multiple

ALT value closest to that of the control group was observed in

Table 1. Laboratory results of the study groups Study groups Control group

Laboratory results (Means±SD) Creatinine (mg/dl)

Cr. Cl (ml/min)

ALT (IU/L)

Na (mmol/L)

K (mmol/L)

0.48±0.12

1.86±0.31

57.97±17.2

135.15±20.12

6.5±1.26

0.53±0.11

0.14±0.12

106.63±26.39

157.78±40.16

7.77±2.02

0.85±0.33

0.54±0.22

225.9±108.57

134.79±14.87

8.15±2.41

0.83±0.7

1.35±0.48

276.22±152.25

133.02±8.37

7.47±0.85

1.5±1.34

1.01±0.16

195.45±17.06

138.4±3.69

9.44±1.36

1.21±1.75

0.63±0.4

259.2±128.04

135.6±6.73

7.36±1.08

21.46

7.59

11.27

Crush plus 2. hours group Crush plus 24. hours group Crush plus Acetaminophen group Crush plus Mannitol group Crush plus Acetaminophen plus Mannitol group Kruskal Wallis

7.64

29.31

0.177

0.0001 0.001 0.180 0.048

SD: Standard deviation; Cr. Cl: Creatinine clearance; ALT: Alanine aminotransferase; Na: Sodium; K: Potassium.

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groups were statistically significant (p<0.05), no statistically significant difference was observed between the group administered mannitol and the other groups (p>0.05), a finding determined using Dunn’s multiple comparison test.

the 2-hour compression group (106.63±26.39 IU/L). Among the treatment groups, the lowest mean ALT value was observed in the mannitol group (195.45±17.06 IU/L), while the highest mean ALT value was observed in the acetaminophen group (276.22±152.25 IU/L; p=0.001).

Scores indicating hydropic degeneration, tubular necrosis, and inflammation are shown in Table 2. Immunoperoxidase and myoglobin, tubulus epithelial cell degeneration, and PAS plus protein scores are shown in Table 3.

While ALT difference between the control and treatment groups was statistically significant (p<0.05), no significant difference was observed between the 24-hour compression group and the acetaminophen or mannitol groups (p>0.05), a finding obtained using Dunn’s multiple comparison test.

While extreme or very extreme hydropic degeneration was observed in 100% of rats in the 2- and 24-hour untreated groups, moderate, extreme or very extreme hydropic degeneration was observed in 50% of the acetaminophen group, 100% of the mannitol group, and 100% of the group receiving both acetaminophen and mannitol treatment. No hydropic degeneration was observed in 16.66% of the acetaminophen group. Difference in intergroup hydropic degeneration was statistically significant (p=0.0001).

Mean sodium value closest to that of the control group was observed in the 24-hour compression group (134.79±14.87 mmol/L). Among the treatment groups, the lowest mean sodium value was found in the acetaminophen group (133.02±8.37 mmol/L), while the highest was observed in the mannitol group (138.4±3.69 mmol/L; p=0.180). Mean potassium value closest to that of the control group was found in the group that had been administered both acetaminophen and mannitol (7.36±1.08 mmol/L). This group also had the lowest mean potassium value. Among the treatment groups, the highest mean potassium value was observed in the mannitol group (9.44±1.36 mmol/L; p=0.048). While differences in potassium between the control and treatment

While moderate, extreme, or very extreme tubular necrosis was observed in 100% of rats in the 2- and 24-hour untreated groups, moderate tubular necrosis was observed in 16.6% of the group receiving acetaminophen treatment, 66.6% of the group receiving mannitol treatment, and 66.6% of the group receiving both acetaminophen and mannitol treatment. Inter-

Table 2. Scores of hydropic degeneration, tubular necrosis, and inflammation in groups (+: mild; ++: moderate; +++: severe; ++++: very severe)

Scores

Group Control

2 hours

Crush groups 24 hours

Acetaminophen

Mannitol

Acetaminophen plus mannitol

(+)

(++)

(+++)

(++++)

χ²:62.61 p=0.0001

(+)

(++)

(+++)

(++++)

χ²:65.61 p=0.0001

Inflammation No

(+) 0 0 0

(++) 0 5

(+++) 0

(++++) 0

χ²:63.12 p=0.000

HD: Hydropic degeneration; TN: Tubular necrosis.

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group tubular necrosis difference was statistically significant (p=0.0001). Moderate, extreme, or very extreme inflammation was observed in 100% of the 2- and 24-hour untreated groups. However, inflammation was observed in 0% of the group receiving acetaminophen treatment, 83.3% of the group receiving mannitol treatment, and 16.6% of the group receiving both acetaminophen and mannitol. Intergroup inflammation was statistically significant (p=0.000). While moderate and extreme immunoperoxidase and myoglobin was observed in 100% of the 2- and 24-hour untreated groups, moderate immunoperoxidase and myoglobin was observed in 16.6% of the acetaminophen group, 33.3% of the mannitol group, and 16.6% of the group receiving both acetaminophen and mannitol. Intergroup difference in immunoperoxidase and myoglobin was statistically significant (p=0.0001). Moderate and extreme tubulus epithelial cell degeneration was observed in 83% of the 2-hour untreated group, and in 100% of the 24-hour untreated groups. Tubulus epithelial cell degeneration was observed in 16.6% of the acetaminophen group, 100% of the mannitol group, and 50% of the group receiving both acetaminophen and mannitol treatment. Intergroup difference in tubulus epithelial cell degeneration was statistically significant (p=0.0001). Moderate and extreme PAS plus protein was observed in

83% of the 2-hour untreated group and in 100% of the 24hour untreated group. PAS plus protein was observed in no rats receiving only acetaminophen treatment, 66.6% of those receiving mannitol treatment, and 50% of those receiving both. Intergroup difference in PAS plus protein was statistically significant (p=0.0001). Statistically significant differences were found between the control and treatment groups regarding hydropic degeneration, tubular necrosis, inflammation, immunoperoxidase and myoglobin, tubulus epithelial cell degeneration, and PAS plus protein, when Dunn’s multiple comparison test was applied (p<0.05). However, no statistically significant difference in these measurements was observed between either the 2- and 24-hour groups or the acetaminophen and mannitol groups (p>0.05). Differences in tubular necrosis and tubulus epithelial cell degeneration between the control and acetaminophen groups were not statistically significant (p>0.05). Neither was significant difference found between the 2-hour and mannitol groups, or the acetaminophen group and the group that had been administered both drugs (p>0.05). Regarding the untreated groups, very extreme findings of hydropic degeneration in 16.6%, of immunoperoxidase and myoglobin in 66.6%, of tubulus epithelial cell degeneration in 16.6%, and PAS plus protein in 16.6% were observed in the 2-hour group. In the 24-hour group, extreme hydropic de-

Table 3. Scores of immunoperoxidase and myoglobin, tubulus epithelial cell degeneration, and PAS plus protein (+: mild; ++: moderate; +++: severe score)

Scores

Group Control

2 hours

Crush groups 24 hours

Acetaminophen

Mannitol

Acetaminophen plus mannitol

(+)

(++)

(+++)

TECD

χ²:59.74 p=0.0001 1

(+)

(++)

(+++)

χ²:65.61 p=0.0001

PASP

No 6 0 0

(+) 0 1 0

(++) 0 4

(+++) 0

χ²:62.78 p=0.0001

IM: Immunoperoxidase and myoglobin; TECD: Tubulus epithelial cell degeneration; PASP: PAS plus protein.

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generation in was observed in 50%, tubular necrosis in 50%, inflammation in 66.6%, immunoperoxidase and myoglobin in 100%, tubulus epithelial cell degeneration in 83.35%, and PAS plus protein was observed in 83.3%. Regarding the treatment groups, hydropic degeneration was not observed in 16.6% of the acetaminophen group, tubular necrosis was not observed in 50%, inflammation was not observed in 50%, immunoperoxidase and myoglobin were not observed in 6.6%, tubulus epithelial cell degeneration was not observed in 16.6%, and PAS plus protein in was not observed in 16.6%. However, these histopathological findings were observed in the mannitol group, in different degrees and rates. In the acetaminophen group, no instances of very extreme hydropic degeneration, tubular necrosis, inflammation, im-

(a)

(d)

munoperoxidase and myoglobin, tubulus epithelial cell degeneration, or PAS plus protein were observed. In the mannitol group, very extreme tubulus epithelial cell degeneration was observed in 100% and PAS plus protein in 66.6%. Very extreme histopathological findings were not found in any rats that received both acetaminophen and mannitol. Histological changes are shown in groups of 24 hours in Figure 2. Observed in untreated compressed groups were diffuse traumatic damage in muscle bundles, inflammatory infiltration, congestion and edema, intense immunoperoxidase and myoglobin in the lumen and glomerulus structure, and PAS and myoglobin in the lumen and glomerulus structure. In damaged muscle tissue histology of the acetaminophen group, sporadic PNL infiltration, myoglobin and immune dyeing in the renal glomerulus and lumen, and normal appearance

(g)

(b)

(e)

(h)

(c)

(f)

(i)

Figure 2. Histologic structure visualized in groups at 24 hours. (a) Crush without treatment, typical traumatic damage in muscle bundles, clear inflammatory infiltration, congestion, and oedema (hematoxylin-eosin, 200x). (b) Crush without treatment, intense immunoperoxidase and myoglobin in the lumen and glomerulus structure (immunoperoxidase, 200x). (c) Crush without treatment, PAS and myoglobin in the lumen and glomerulus structure (PAS, 200x). (d) Crush with acetaminophen treatment, damaged muscle tissue histology, sporadic PNL infiltration that followed (hematoxylin-eosin, 200x). (e) Crush with acetaminophen treatment, myoglobin and immune dye in the renal glomerulus and lumen are not followed (immunoperoxidase, 200x). (f) Crush with acetaminophen treatment, normal appearance of renal tubulus lumen and glomerulus structure histology (PAS, 200x). (g) Crush with acetaminophen plus mannitol treatment, sporadic tubular immunoperoxidase and myoglobin presence (immunoperoxidase, 200x). (h) Crush with mannitol treatment, sporadic tubular immunoperoxidase and myoglobin presence is followed (immunoperoxidase, 200x). (i) Crush with mannitol treatment, PAS plus myoglobin in lumen and glomerulus structure (PAS, 200X).

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of renal tubulus lumen and glomerulus structure histology were observed. In the group that had been administered acetaminophen plus mannitol treatment, sporadic tubular immunperoxidase and myoglobin were observed. In the group that was administered only mannitol treatment, sporadic tubular immunperoxidase and myoglobin were observed, as were PAS and myogobin in the lumen and glomerulus structure.

DISCUSSION New treatment protocols are needed in order to increase rates of survival during rescues from rubble in the aftermath of earthquakes, as well as survival from other types of crush that cause wide-scale death and injury.[11–16,25–28] In a rat model-based study, radical derivatives of rhabdomyolysis emerging as a result of redox reactions between ferric and ferryl myoglobin was shown to cause serious oxidative damage to kidneys.[29] Several clinical and animal studies have been conducted using a number of active substances that behaved as metal-ion inactivators with the intention of aiding in the recovery of oxidative damage, scavenging free radicals, stimulating physiological enzymatic antioxidant systems, and protecting mitochondrial functions.[17,30–33] It was presently understood that a closed, piston-activated compression model most accurately mimicked factors causing crush trauma in earthquakes.[20–22] In animal experiments with ischemia-reperfusion models, it was shown that disruption of circulation in the extremities increased muscle damage. After removal of pressure on the extremity, myoglobin-containing oxidative ferrous derivatives that may cause cell injury, hemoglobin, lactic acid, potassium, and creatinine are released during the reperfusion. Following crush injury, change in electrolytes occurs both inside and outside the cell, and sodium-potassium-ATPase activity in the cell membrane deteriorates.[34–36] No statistically significant decrease in sodium level was observed in the present study. However, in accordance with the findings of others, an increase in potassium was observed in all groups at the 24th hour.[16,37] In addition, it has been shown that mannitol and acetaminophen should be administered together to prevent hyperpotassemia in crush treatment. Various treatments have been utilized in an attempt to decrease the extent of kidney damage following crush injury. [27,28,30,31] The lowest mean creatinine value among treatment groups, as well as the highest mean rate of creatinine clearance, were found in the acetaminophen group, while the highest creatinine level was found in the mannitol group. These results are thought to be linked to the protective effect of acetaminophen on kidney function. Tolouian R. et al. report312

ed similar prophylactic benefits in studies using oral alkaline solutions.[27] Compared to the acetaminophen group, creatinine was increased and creatinine clearance was decreased in the mannitol group. When mannitol was administered in conjunction with acetaminophen, creatinine decreased, though creatinine clearance was not increased. Although creatinine kinase levels were high in the compressed groups, serum creatinine kinase level has low specificity in rhabdomyolysis.[38] The most important substance secreted from muscles during rhabdomyolysis is myoglobin; levels rise and fall much faster than creatinine kinase levels (in 1–6 hours). In addition, myoglobinuria is not always visible, or may be resolved early.[39] Therefore, myoglobin and creatinine kinase levels were not evaluated in the present study. It has been observed that enzymes in the liver are also very high in days following crush trauma, as are other biomarkers.[40] It was presently believed that use of acetaminophen and mannitol potentially decreased liver damage, as ALT values began to increase following compression, and the highest values were observed in the acetaminophen group, lowering when mannitol was added to treatment. It was presently observed that ALT levels were higher in the acetaminophen group, compared to the mannitol group, an effect that decreased when mannitol was added to acetaminophen treatment. However, administration of N-acetylcysteine, an easily found, cheap antidote, in addition to mannitol, creates an advantage in terms of therapeutic application safety. In an in-vitro study, Boutaud O. et al.[18] showed that acetaminophen decreased ferryl heme transformation into ferric form, inducing lipid peroxidation of hemoproteins, and promoting the formation of globin radicals, results also demonstrated in in-vitro and in-vivo studies conducted by Nath KA et al.[19] In a separate study by Boutaud O. et al., chemical crush was induced in rats with glycerol. It was demonstrated that acetaminophen was very useful due to its antioxidant feature, cytoprotective effects, and protection against organ damage, and is also cheap, accessible, and suitable for use in all populations, including pregnant women.[17] Few studies (either clinical or animal) have raised questions regarding the use of mannitol to treat crush injury, including vasodilatory or cytoprotective effects.[16,18] It was also observed that the extremity of hydropic degeneration, tubular necrosis, inflammation, immunoperoxidase and myoglobin, tubulus epithelial cell degeneration, and PAS plus protein findings were elevated in the 2nd hour, compared to Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

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the control group, as well as in the 24th hour, compared to the 2-hour and control groups. It was also observed that these levels were lower in the acetaminophen group, compared to the mannitol group. When acetaminophen and mannitol were administered together, findings were better than those of the mannitol group, but worse than those of the acetaminophen group. As a result of immunohistochemical and histopathological evaluation, it was determined that acetaminophen treatment decreased PAS plus dyed protein material presence in kidney tissue, myoglobin, and glomerulus capillary lumen. Compared to other treatments studied, acetaminophen had demonstrated preventative effects on hydropic degeneration, inflammation, tubular necrosis, and tubulus epithelial cell degeneration.

Conclusion Results of the present experimental study demonstrate that acetaminophen is more effective than mannitol in the treatment of crush injury. Acetaminophen ameliorates histopathological renal damage and protects renal functions. When acetaminophen and mannitol are used in conjunction, the positive effects of acetaminophen are decreased, the protective effects of mannitol against renal damage and function are increased, and the toxic effect of acetaminophen on the liver is decreased, compared to treatment of acetaminophen alone. Furthermore, hyperpotassemia that occurs when mannitol is administered in isolation decreases when either acetaminophen or acetaminophen + mannitol are administered. These findings warrant further studies, prior to clinical implementation.

Acknowledgement We would like to thank to Prof. Ahmet KAZEZ of the Fırat University Medical School Pediatric Surgery Department for allowing the use of the tissue compression device. Conflict of interest: None declared.

REFERENCES 1. Sever MS, Vanholder R; RDRTF of ISN Work Group on Recommendations for the Management of Crush Victims in Mass Disasters. Recommendation for the management of crush victims in mass disasters. Nephrol Dial Transplant 2012;27 Suppl 1:1–67. 2. Ashkenazi I, Isakovich B, Kluger Y, Alfici R, Kessel B, Better OS. Prehospital management of earthquake casualties buried under rubble. Prehosp Disaster Med 2005;20:122–33. 3. Reis ND, Better OS. Mechanical muscle-crush injury and acute musclecrush compartment syndrome: with special reference to earthquake casualties. J Bone Joint Surg Br 2005;87:450–3. 4. Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin 1999;15:415–28. 5. Smith J, Greaves I. Crush injury and crush syndrome: a review. J Trauma 2003;54(5 Suppl):226–30. 6. Rosedale KJ, Wood D. Traumatic rhabdomyolysis (crush syndrome) in

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the rural setting. S Afr Med J 2011;102:37–9. 7. Sever MS, Erek E, Vanholder R, Akoğlu E, Yavuz M, Ergin H, et al. The Marmara earthquake: epidemiological analysis of the victims with nephrological problems. Kidney Int 2001;60:1114–23. 8. Ron D, Taitelman U, Michaelson M, Bar-Joseph G, Bursztein S, Better OS. Prevention of acute renal failure in traumatic rhabdomyolysis. Arch Intern Med 1984;144:277–80. 9. Better OS. The crush syndrome revisited (1940-1990). Nephron 1990;55:97–103. 10. Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med 2006;354:1052–63. 11. Better OS, Stein JH. Early management of shock and prophylaxis of acute renal failure in traumatic rhabdomyolysis. N Engl J Med 1990;322:825– 9. 12. Evans KJ, Greenberg A. Hyperkalemia: a review. J Intensive Care Med 2005;20:272-90. 13. Better OS. Rescue and salvage of casualties suffering from the crush syndrome after mass disasters. Mil Med 1999;164:366–9. 14. Eneas JF, Schoenfeld PY, Humphreys MH. The effect of infusion of mannitol-sodium bicarbonate on the clinical course of myoglobinuria. Arch Intern Med 1979;139:801–5. 15. Gadallah MF, Lynn M, Work J. Case report: mannitol nephrotoxicity syndrome: role of hemodialysis and postulate of mechanisms. Am J Med Sci 1995;309:219–22. 16. Brown CV, Rhee P, Chan L, Evans K, Demetriades D, Velmahos GC. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma 2004;56:1191–6. 17. Boutaud O, Moore KP, Reeder BJ, Harry D, Howie AJ, Wang S, et al. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure. Proc Natl Acad Sci U S A 2010;107:2699–704. 18. Boutaud O, Aronoff DM, Richardson JH, Marnett LJ, Oates JA. Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H(2) synthases. Proc Natl Acad Sci U S A 2002;99:7130– 5. 19. Nath KA, Balla J, Croatt AJ, Vercellotti GM. Heme protein-mediated renal injury: a protective role for 21-aminosteroids in vitro and in vivo. Kidney Int 1995;47:592–602. 20. Özel ŞK, Köseoğulları AA, Kazez A, Akpolat N, İlhan N. Ezilme yaralanması oluşturulan sıçanlardaki böbrek hasarına melatoninin etkisi. Çocuk Cerrahisi Dergisi 2006;20:105–10. 21. Özel ŞK, Kazez A. Karın, genitoüriner ve toraks travma modelleri. In: Çakmak AM, Karagüzel G, Soyer T, Günaydın S, Karahan S, editör. Çocuk Cerrahisinde Deneysel Araştırmalar. Ankara: Özkan Matbaacılık; 2009. s. 170–5. 22. Speck K, Schneider BS, Deashinta N. A rodent model to advance the field treatment of crush muscle injury during earthquakes and other natural disasters. Biol Res Nurs 2013;15:17–25. 23. Szewczyk D, Ovadia P, Abdullah F, Rabinovici R. Pressure-induced rhabdomyolysis and acute renal failure. J Trauma 1998;44:384–8. 24. Matsen FA 3rd, Mayo KA, Sheridan GW, Krugmire RB Jr. Monitoring of intramuscular pressure. Surgery 1976;79:702–9. 25. de Bruycker M, Greco D, Annino I, Stazi MA, de Ruggiero N, Triassi M, et al. The 1980 earthquake in southern Italy: rescue of trapped victims and mortality. Bull World Health Organ 1983;61:1021–5. 26. Cho YS, Lim H, Kim SH. Comparison of lactated Ringer’s solution and 0.9% saline in the treatment of rhabdomyolysis induced by doxylamine intoxication. Emerg Med J 2007;24:276–80. 27. Tolouian R, Wild D, Lashkari MH, Najafi I. Oral alkalinizing solution as a potential prophylaxis against myoglobinuric acute renal failure: preliminary data from healthy volunteers. Nephrol Dial Transplant 2005;20:1228–31.

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Nephrol 2000;11:1553–61. 35. Better OS, Rubinstein I, Reis DN. Muscle crush compartment syndrome: fulminant local edema with threatening systemic effects. Kidney Int 2003;63:1155–7. 36. Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002;10:620–30. 37. Sever MS, Erek E, Vanholder R, Kantarci G, Yavuz M, Turkmen A, et al. Serum potassium in the crush syndrome victims of the Marmara disaster. Clin Nephrol 2003;59:326–33. 38. Kenney K, Landau ME, Gonzalez RS, Hundertmark J, O’Brien K, Campbell WW. Serum creatine kinase after exercise: drawing the line between physiological response and exertional rhabdomyolysis. Muscle Nerve 2012;45:356–62. 39. Keltz E, Khan FY, Mann G. Rhabdomyolysis. The role of diagnostic and prognostic factors. Muscles Ligaments Tendons J 2014;3:303–12. 40. Weibrecht K, Dayno M, Darling C, Bird SB. Liver aminotransferases are elevated with rhabdomyolysis in the absence of significant liver injury. J Med Toxicol 2010;6:294–300.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Ezilme yaralanması oluşturulan sıçanlarda asetaminofen ve mannitolün etkileri: Deneysel çalışma Dr. Mustafa Ferudun Çelikmen,1 Dr. Sezgin Sarıkaya,1 Dr. Doğaç Niyazi Özüçelik,2 Dr. Mehmet Şükrü Sever,3 Dr. Kurtuluş Açıksarı,4 Dr. Deniz Maktav Çelikmen,5 Dr. Mustafa Yazıcıoğlu,6 Dr. Ali Kandemir,1 Dr. Halil Doğan,6 Dr. Barış Murat Ayvacı,7 Dr. Derya Özaşır Abuşka,8 Dr. Sıla Sadıllıoğlu9 Yeditepe Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İstanbul İstanbul Üniversitesi Sağlık Bilimleri Fakültesi, İstanbul 3 İstanbul Üniversitesi Tıp Fakültesi, Nefroloji Bilim Dalı, İstanbul 4 İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İstanbul 5 Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, İç Hastalıkları Kliniği, İstanbul 6 Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul 7 Okmeydanı Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul 8 Haseki Eğitim ve Arşatırma Hastanesi, Acil Tıp Kliniği, İstanbul 9 İstanbul Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul 1 2

AMAÇ: Bu çalışmada, mekanik ezilme yaralanması oluşturulan sıçanlarda, asetaminofen ve mannitolün böbrek fonksiyonu ve histopatolojisi üzerine etkileri araştırıldı. GEREÇ VE YÖNTEM: Çalışmada 370–400 gram ağırlığında 36 sıçan kullanıldı. Kontrol amaçlı birinci gruba bir işlem uygulanmadı. Diğer beş gruba ikişer saat süresince her iki bacak gastroknemius kası bölgesine mekanik ezilme işlemi uygulandı. Sonra dördüncü gruba asetaminofen 100 mg/kg; beşinci gruba mannitol 1 gr/kg; altıncı gruba asetaminofen 100 mg/kg ve mannitol 1 gr/kg intraperitoneal verildi. Herhangi bir tedavi uygulanmayan ikinci grup iki saat sonra, üçüncü grup ve tedavi grupları ise 24 saat sonra sakrifiye edilerek kan ve doku örnekleri alındı. BULGULAR: Sodyum, potasyum, alanin aminotranferaz, kreatinin, ortalama kreatinin klirensi değerleri açısından asetaminofen ve mannitol tedavi grupları arasında istatistiksel olarak anlamlı fark bulunmadı. Histopatolojik olarak hidropik dejenerasyon, tübüler nekroz, enflamasyon, tubulus lümeninde immünoperoksidaz ve miyoglobin varlığı, tubulus epitel hücre dejenerasyonu, tubulus lümeninde PAS boyanan materyel varlığı bulgularının mannitol uygulanan grupta azaldığı, asetaminofen uygulanan grupta mannitol uygulanan gruptan daha fazla azaldığı, asetaminofenle mannitol birlikte uygulandığında ise bulguların tek başına mannitol uygulamasından daha iyi, ancak tek başına asetaminofen uygulamasından daha iyi olmadığı görüldü. TARTIŞMA: Ezilme yaralanmalarında oluşan böbrek hasarında asetaminofen histopatolojik olarak mannitolden daha etkilidir. Asetamniofen mannitolle birlikte kullanıldığında ise karaciğere olan toksik etkisi daha az olmaktadır. Anahtar sözcükler: Asetaminofen; böbrek hasarı; deprem; deneysel çalışma; ezilme yaralanması; mannitol. Ulus Travma Acil Cerrahi Derg 2016;22(4):305–314

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doi: 10.5505/tjtes.2015.76824

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EXPERIMENTAL STUDY

Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model Ömer Faik Ersoy, M.D.,1 Namık Özkan, M.D.,1 Zeki Özsoy, M.D.,1 Hüseyin Ayhan Kayaoğlu, M.D.,1 Erdinç Yenidoğan, M.D.,1 Alper Çelik, M.D.,1 Aziz Fikret Özuğurlu, M.D.,2 Ebru Arabacı Çakır, M.D.,3 Neşe Lortlar, M.D.4 1

Department of General Surgery, Gaziosmanpasa University Faculty of Medicine, Tokat-Turkey

Department of Biochemistry, Gaziosmanpasa University Faculty of Medicine, Tokat-Turkey

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

Department of Histology and Embryology, Gazi University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: The present objective was to identify effects of early melatonin application on healing of anastomotic wound and inflammation in an experimental sepsis model. METHODS: A total of 60 Wistar albino rats were divided into 2 groups. Cecal ligation puncture (CLP) and colonic resection anastomosis were performed on both the control group and the melatonin treatment group. Both groups were divided into 3 subgroups consisting of 10 rats each. One subgroup from each group underwent re-laparotomy at the 16th hour, the next on the 3rd day, and the final subgroup on the 7th day. Presently evaluated were effects of melatonin treatment of early sepsis on interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (INF-γ), and C-reactive protein (CRP) levels, as well as burst pressures (BPs), collagen and hydroxyproline (OHP) content of the anastomotic segments, histopathologic healing, immunohistochemical expressions, CD34, and transforming growth factor beta (TGF-β). RESULTS: IL-6 and INF-γ levels of the treatment group showed a significant decrease at the 16th hour and an increase on the 3rd and 7th postoperative days. IL-10 levels were significantly higher at the 16th hour and significantly lower on the 3rd and 7th postoperative days in the control group (p<0.001 for each). The treatment group also showed significantly higher capillary permeability, fibroblast proliferation, and collagen deposits (p<0.001 for each). CD34 expression was significantly increased in the treatment group on the 7th postoperative day (p=0.005). CONCLUSION: Application of melatonin in early sepsis significantly improved colonic anastomotic healing in a rat model. Keywords: Anastomosis; colon; melatonin; sepsis.

INTRODUCTION Surgery of the colon represents a large share of all surgeries performed in clinical practice. Many factors, some related to the surgeon, affect the success of anastomosis.[1] In spite of improvements in surgical techniques and stapling devices, Address for correspondence: Erdinç Yenidoğan, M.D. Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tokat, Turkey Tel: +90 356 - 212 21 84 E-mail: claritromisin@yahoo.com Qucik Response Code

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gastrointestinal anastomoses remain associated with significant morbidity. Sepsis, a well-known etiology of anastomotic breaks, has been the subject of investigation in a number of studies. Sepsis is the response of the body to infections generally bacterial in origin. Endotoxemia results in the elaboration of soluble mediators that enhance cellular effector mechanisms, increase in procoagulant and fibroblast activity to localize the invaders, and increase in microvascular blood flow to enhance delivery of immune cells to the source of the sepsis in an attempt to eradicate the pathogens. This systemic response is commonly associated with multiple organ damage, which can lead to death. In cases of septic shock, vasodilatory effects are caused in part to up-regulation of nitric oxide (NO) in the vessel wall. This potent agent plays a central role in diminishing vascular tone, and resists vasoconstrictors.[2] The interaction between pathogens and host leads to activation of macrophages, complement proteins, 315

Ersoy et al. Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model

and immunoglobulins. Excretion of cytokines such as tumor necrosis factor alpha (TNF-α), interferon gamma (INF-γ), and interleukins (ILs) takes place, depending on the magnitude of the response. Polymorphonuclear leukocyte attraction also occurs. These host defense mechanisms lead to further influx of inflammatory fluid into the area of infection, a process that begins within several minutes and may peak within hours.[3] The pineal hormone melatonin plays a fundamental role in the neuro-immuno-endocrine system. Melatonin modulates the immune system with monocyte cytokines, fibroblast proliferation, and growth hormones, which influence angiogenesis.[4] Beneficial effects of melatonin are the product of its effects on antioxidant potential, free-radical scavenger activity, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation, as well as NO expression and nitrite production. NF-κB acts in the modulation of DNA transcription, a critical point in the regulation of cellular processes, such as DNA repair, as well as conditions that require cellular growth, such as sepsis. Melatonin also inhibits the lipopolysaccharide-induced increase in MAPK activation, which promotes tissue inflammation and injury.[5–8] Recent studies have demonstrated the beneficial effects of melatonin on healing of gastric and duodenal ulcers, as well as burn injuries.[9,10] However, the effect of melatonin on colonic healing remains controversial. In the present study, effects of melatonin treatment on cytokine response and colonic anastomotic healing in a sepsis model were evaluated.

MATERIALS AND METHODS Experiment Protocol Approval of the ethics committee was obtained prior to the start of the study and was based on experiment protocol. All rats received professional human care at the experimental research center. Sixty Wistar albino rats of both sexes, weighing 220–300 g each, were fasted for 12 hours, with free access to water, prior to experiment initiation. Rats were housed (2–3 per wire cage) in an environment with a 12-hour light-dark cycle at a constant temperature of 22–23ºC, and were fed a standard diet. Rats were divided into 2 groups: treatment and control. All rats underwent cecal ligation puncture (CLP) followed by cecal resection, partial colonic resection, and anastomosis. Both groups were then divided into 3 subgroups (16th hour, 3rd day, and 7th day), each consisting of 10 rats. Sepsis was induced by CLP technique modified by Fujimura et al.[11] Anesthesia of xylazine (10 mg/kg) and ketamine hydrochloride (75 mg/kg) was administered. Following skin preparation, midline laparotomy of 2–3 cm was made, and the cecum was ligated just below the ileocecal valve with 3–0 silk in order to maintain intestinal continuity. The cecum was perforated in 2 locations, 1 cm apart, on the antimesenteric surface, using an 18-gauge needle, and gently compressed until the extrusion of feces was observed. Six hours later, 316

the cecum was resected next to the ileocecal valve. Then, the descending colon was mobilized and a 5-mm segment, approximately 2–3 cm above the peritoneal reflection, was resected. Next, single-layered, end-to-end anastomosis was performed by the same surgeon, using 5-0 polypropylene (Prolene; Ethicon, Inc., Somerville, NJ, USA) with interrupted inverting sutures. The fascia and skin were closed with 4–0 monofilament running sutures. All animals were resuscitated with subcutaneous injection of 5 mL saline.

Melatonin Treatment Melatonin was dissolved in absolute ethanol, and further dilutions were made in saline. Final concentration of ethanol was 1%. Either melatonin (10 mg/kg) or 1% alcohol in saline (1 mL/kg) was intraperitoneally administered 30 minutes prior to and 6 hours after surgery, in order to investigate the role of melatonin in the early inflammatory phase of sepsis.[12]

Burst Pressure All animals were decapitated following induction of anesthesia. Following re-laparotomy performed by an investigator blinded to grouping, a 5–6 cm portion of a colonic segment with anastomosis was resected. Luminal content was cleansed by gentle saline flushing. In order to evaluate burst pressures (BPs) of the anastomotic segments, 1 end of the colonic segment was tightly sutured with 3–0 silk, and the other was attached to a mercury manometer by a tubing piece with an infusion pump. The colon segment was then placed in a saline-filled container, and air was pumped at a constant pressure of 10 mmHg/sec. As previously described, the pressure at which values suddenly declined or air bubbles were observed was recorded as BP.[13] Potential upper limit of the apparatus was 300 mmHg. For this reason, values higher than 300 mmHg were recorded as 300 mmHg.

Hydroxyproline Determination in the Intestines Tissue samples obtained for hydroxyproline (OHP) determination were washed with serum physiologic and dried at 100ºC for 72 hours. OHP levels were determined spectrophotometrically by Woessner method.[14] Samples were first weighed and hydrolyzed by dense hydrochloric acid (12 mol/L hydrogen chloride) at 130ºC for 3 hours. Each sample was adjusted to 1 mL final volume. Samples were centrifuged at 3000 x g for 15 minutes to obtain a supernatant. A second centrifugation at 2500 x g was performed for 10 minutes after isopropanol was added to an equal volume of the supernatant. Serial dilutions of commercial pure OHP were used as a standard. OHP concentrations of the samples were calculated using the absorbance–concentration curve of standard OHP solutions. Results were expressed as mg/g dry tissue. All samples were assayed in duplicate.

Histopathology For light microscopic study, anastomotic segments were fixed Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

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in 10% formaldehyde for 72 hours. The tissues were washed under running tap water and dehydrated with 50%, 60%, 70%, 80%, 90%, 96%, and 100% concentrated ethanol, then placed in a 1:1 ratio of immersion oil and absolute alcohol for 1 hour, followed by immersion oil overnight, to achieve transparency. After the application of xylol, specimens were poured into paraffin blocks using a 1:1 xylol and paraffin mixture for 1 hour and into paraffin for 6 hours in an incubator. Paraffinembedded tissues were sectioned at 5 µm and stained with hematoxylin-eosin. Additional sections were stained with Masson’s trichrome. During histopathological analysis, healing parameters (fibroblast infiltration, capillary formation) and inflammatory changes (granulocyte and mononuclear cell infiltration) in each specimen were semiquantitatively assessed by assigning a score of 0–3 for each parameter, as described.[15] Presence or absence of necrosis, exudate, epithelialization, and peritonitis were also recorded. Masson’s trichrome stain was assessed for the presence or absence of regular collagen fiber pattern as follows: No regular collagen fibers = 0 Mildly regular collagen fibers = 1 Moderately regular collagen fibers = 2 Severely regular collagen fibers = 3

Measurement of Cytokines and C-reactive Protein Blood samples were collected at the 16th postoperative hour, and on the 3rd and 7th postoperative days. Samples were centrifuged and stored at -20ºC until analysis was performed. Interleukin-6 (IL-6), interleukin-10 (IL-10), INF-γ, and C-reactive protein (CRP) levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) by automatic micro ELISA Tritus analyzer (Grifols, S.A., Barcelona, Spain). Rat IL-6, IL-10, INF-γ, and CRP ELISA kits (MyBioSource, Inc., San Diego, CA, USA) were used.

Immunohistochemical Method Avidin-biotin-peroxidase complex techniques were used for immunohistochemical staining.[16] The slides were incubated overnight at 37ºC, then for 1 hour at 60ºC. Next, they were de-waxed in 2 cycles of xylene (15 minutes each) and rehydrated with descendent ethyl alcohol gradient for 10 minutes each, followed by 2 5-minute changes of distilled water. The sections were boiled in citrate buffer in a microwave oven for 5 minutes at 650 W and for 3x5 minutes at 550 W. After 20 minutes at room temperature, the tissues were rolled with a PAP pen (Beckman Coulter Inc., Brea, CA, USA). The tissues were washed with distilled water, then with phosphatebuffered saline (PBS), and endogenous peroxidase activity in the tissues was blocked in 3% hydrogen peroxide for 20 minutes. PBS-diluted Ultra V block (Thermo Fisher Scientific, Inc., Waltham, MA, USA) was applied for 5 minutes. Following 1-hour application of primary antibodies— transforming growth factor beta 3 (TGF-β3; Vet Pharma Friesoythe GmbH, Friesoythe, Germany) and CD34 (Lab Vision/Neomarkers, Inc., Freemont, CA, USA)— diluted with antibody diluents Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

(Thermo Fisher Scientific, Inc., Waltham, MA, USA), the samples were washed with PBS. Secondary antibody— biotinylated anti-polyvalent— was applied for 20 minutes. After the slides were washed with PBS, they were exposed to streptavidin peroxidase for 20 minutes. The specimens were rewashed with PBS and placed in 3-amino-9-ethylcarbazole (AEC) chromogen for 10 minutes. Finally, counter-staining with Mayer’s hematoxylin was performed for 2 minutes. All slides were evaluated using a Leica DMI 4000B light microscope (Leica Microsystems GmbH, Wetzlar, Germany) and photographed with Leica QWin Pro (version 3.4.0; Calidris & SoftHard Technology Ltd., Marianka, Slovakia). Two researchers blinded to grouping independently evaluated staining intensity. The following staining intensity designation was used: 0 for no involvement; 1 (+) for slight involvement; 2 (++) for mild involvement; and 3 (+++) for strong involvement of the primary antibody. The entire slide of each specimen was examined, and final scoring was based upon the predominant areas with the highest grade of staining intensity. Labelling intensity was graded semi-quantitatively, and HSCORE was calculated using the following equation: HSCORE =Pi(i + 1), where i is the intensity of labelling with a value of 1, 2, or 3 and Pi is the percentage of labelled epithelial and stromal cells for each intensity, varying from 0–100%.[17]

Statistical Analysis Statistical evaluation of numeric variables was performed with 1-way analysis of variance, followed by post-hoc Tukey. Nonnumeric variables were evaluated with χ2 test. A p value of less than 0.05 was considered statistically significant.

RESULTS Two mortalities were observed in the control group: at the 16th postoperative hour and on the 3rd postoperative day. Statistical analysis was performed excluding these mortalities. BPs and OHP levels are shown in Table 1. BP levels were slightly higher but insignificant in the treatment group at the 16th hour and on the 3rd day (p=1.0 and p=0.99, respectively). BP elevation was statistically significant in the treatment group on the 7th day (146.1±50.74 mmHg vs 193.0±26.58 mmHg, p<0.001). OHP levels at the anastomotic site showed significant improvement in the treatment group (77.73±24.87 µg/ mg vs 132.26±48.48 μg/mg at the 16th hour; 129.5±13.6 μg/ mg vs 197.07±56.52 μg/mg on the 3rd day; and 198.31±33.59 μg/mg vs 224.67±61.16 μg/mg on the 7th day in the control and treatment groups, respectively; p=0.008, p=0.016, and p=0.01, respectively). Histologically, fibroblastic proliferation and capillary permeability as indicators of wound healing were improved in the treatment group, with statistically significant difference (p<0.001, Figs. 1, 2). Collagen deposits showed significantly better deposition, by Masson’s trichrome staining, in the 317

Ersoy et al. Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model

Table 1. Burst pressures and hydroxyproline levels in all groups

Sacrification time

Control

Burst pressure (mmHg)

16th hour

Treatment (Melatonin)

Mean±SD Mean±SD 7.40±5.25

8.33±5.46

=1.0

Third POD

40.0±15.09

45.89±10.52

=0.99

Seventh POD

146.1±50.74

193.0±26.58

<0.001*

Hydroxyproline-Proline Level (μg/mg)

16th hour

77.73±24.87

132.26±48.48

=0.008*

Third POD

129.5±13.6

197.07±56.52

=0.016*

Seventh POD

198.31±33.59

224.67±61.16

=0.01*

*Melatonin-treated rats had significantly elevated BP on the seventh POD and higher OHP levels in all periods examined. SD: Standard deviation.

treatment group (p<0.001, Fig. 3). Demonstrative histological sections are shown in Figure 4a-d. Fibroblast Absence

Mild Moderate

†



Count

Severe



Cytokine levels differed significantly over time. In the treatment group, inflammatory cytokines (IL-6 and INF-γ) were significantly lower at the 16th hour and significantly higher during the 3rd and 7th postoperative days (p<0.001 for each). Levels of regulatory cytokine (IL-10) were significantly higher at the 16th hour and significantly lower on the 3rd and 7th postoperative days (p<0.001 for each). CRP levels were also significantly lower in the treatment group at the 16th hour. CRP levels of the treatment group tended to be lower than those of the control group on the 3rd and 7th postoperative days, but the difference was not statistically significant (p=0.38 and p=0.99, respectively). Cytokine and CRP levels are shown in Table 2.

Control 16h

Control 3rd day

Control 7th day

Treatment Treatment Treatment 16h 3rd day 7th day

Groups

Immunohistochemical evaluation of CD34 revealed similar results between the groups at the 16th hour (p=1.0). On the 3rd postoperative day, the treatment group showed a slight increase in CD34 levels, but the difference was not statistically significant (p=0.057). On the 7th postoperative day, CD34

Figure 1. Fibroblastic proliferation was significantly improved in the treatment group at the 3rd and 7th postoperative days (p<0.001).



8 Capillar Absence

†



Mild

†



Count

Severe

 Count

†

Moderate

MSS Absence Mild Moderate Severe

2 0 0

Control 16h

Control 3rd day

Control Treatment Treatment Treatment 7th day 16h 3rd day 7th day Groups

Figure 2. Capillary formation, an indicator of wound healing, increased over time in the treatment group, with significant difference (p<0.001).

318

Control 16h

Control 3rd day

Control 7th day

Treatment Treatment Treatment 16h 3rd day 7th day

Groups

Figure 3. Collagen deposition was evaluated by Masson’s trichrome staining, and showed significantly better results in the treatment group, particularly at the 3rd and 7th postoperative days (p<0.001).

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Ersoy et al. Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model

Table 3. Transforming growth factor beta expression at the anastomotic site, distributed according to histological examination, showed markedly higher levels in the treatment group at all intervals

(a)

(b)

(c)

(d)

Figure 4. (a) Mild granulocyte, fibroblast infiltration, and capillary formation, (b) moderate granulocyte and fibroblast infiltration, (c) severe granulocyte infiltration, and (d) moderate fibroblast proliferation in the subserosal layer. ([a-c]: Hematoxylin-eosin, x20 magnification; [d] Masson’s trichrome stain, x20 magnification).

Groups Control Treatment p (Melatonin)

n % n %

TGF-β 16th hour Absence

5 55.6

Mild

4 44.4 9 90.0 0

Moderate

Severe

0 0 0 0

0.019

1 10.0

Third POD Absence 0 0 0 0 0.001

(a)

(b)

Mild

9 90.0 2 20.0

Moderate

Severe

0 0 0 0

Absence 0 0 0 0 0.008 Mild

expression of the treatment group was significantly higher (p=0.005) (Fig. 5a, b).

Severe

DISCUSSION Numerous attempts have been made to lower incidence of anastomotic leakage and related complications in cases of colorectal surgery. Effects of melatonin on the integrity of colonic anastomoses in septic conditions were presently investigated with a rat model. The idea of treating septic animals with melatonin originated in the hypothesis that this product had potential antioxidant effects and was a potent free radical scavenger. In another vital effect, melatonin stimulates activity of the endogenous antioxidant enzymes glutathione and myeloperoxidase.[18–20] Melatonin also has immune-regulatory and anti-edematogenic effects. The immune-regulatory effects of melatonin are associated with a reduction in MAPK and NF-κB activation, down-regulation of a variety of proinflammatory cytokines, expression of inducible NO synthase, and production of nitrite.[20–22] The present results demonstrate that melatonin treatment administered during the early phase of sepsis leads to early decline in inflammatory cytokines (IL–6 and INF-γ) and inUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

8 80.0

Seventh POD

Figure 5. (a) Immunohistochemical demonstration of mild, and (b) moderate CD34 expression (x100 magnification).

Expression of TGF-β at the anastomotic site showed significantly higher levels in the treatment group at the 16th postoperative hour, and on the 3rd and 7th postoperative days (p=0.019, p=0.001, and p=0.008, respectively). TGF-β levels are listed in Table 3.

6 60.0

Moderate 2 20.0 8 20.0 2 20.0 0 80.0

crease in levels of regulatory cytokine (IL-10). However, this effect was reversed on the 3rd and 7th postoperative days. IL-10 is able to induce modified cytokine secretion pattern with suppression of TNF-α, IL-l, IL-6, and IL-8, and can inhibit antigen-presenting capacity. IL-10 also has both direct and cytokine-related indirect effects on monocytes and macrophages. Therefore, IL-10 appears to be an important candidate for the induction of immunoparalysis, which frequently follows a hyperinflammatory phase. Interestingly, IL10 inhibits its own production and TNF-α blockade leads to the inhibition of endotoxin-induced IL-10 formation in human monocytes. The purpose of these consecutive inflammation and anti-inflammation phases is to protect the organism against the consequences of whole-body inflammation. Interestingly, 2 peaks of IL-10 production can be detected in vivo. The “late” IL-10 peak can be detected in plasma 8 hours after endotoxin exposure, and is regulated by TNF-α. The “early” IL-10 peak can be detected 1–2 hours after exposure and explains the monocyte deactivation that is observed following trauma. Normally, monocytes recover spontaneously within 24–72 hours. Persistence of deactivation is associated with high rate of infection.[23–25] In the present study, IL-10 levels were initially higher in treated rats and decreased on the 3rd and 7th postoperative days. We believe that immunoregulatory effects of melatonin assisted in the normalization of IL-10 levels, preserving monocyte and macrophage functions. 319

Ersoy et al. Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model

Rate of CRP synthesis directly reflects the intensity of the inflammatory process. Anastomotic leak, wound infection, tissue ischemia, and necrosis activate CRP production.[26,27] In septic patients, decrease in CRP levels indicates a higher survival rate or resolution of sepsis.[28,29] CRP levels were significantly lower in the treatment group at the 16th hour, and remained at levels lower than those of the control group on the 3rd and 7th postoperative days. We believe that the decrease in CRP levels in treated rats confirms the anti-inflammatory role of melatonin during sepsis. Beneficial effects of melatonin on wound healing have been documented. Soybir et al. investigated the role of melatonin in an experimental wound healing model and detected a higher number of macrophages, fibroblasts, neovascularizations, and higher collagen density in treated animals. The authors determined that exogenous melatonin has positive effects on the angiogenic phase of wound healing.[4] As OHP is the main determinant of collagen content within tissue, a correlation exists.[30] In the present study, higher levels of OHP were observed in the treatment group at all times, and significantly higher collagen deposits were also observed. BPs measured on the 7th postoperative day were significantly higher in treated rats. Although insignificant, BP levels were also slightly higher in the treatment group at the 16th hour and 3rd postoperative day. Overall, the present results have demonstrated a correlation between OHP levels, collagen deposits, and BP. According to the data, it can be concluded that exogenous melatonin has regulatory and supportive effects on wound healing and collagenization. Pugazhenthi et al. were the first to demonstrate accelerated wound healing with melatonin in rats. The results also confirmed modulated key biological processes, such as collagen synthesis, scar formation, inflammation, and angiogenesis.[21] However, no consensus regarding the effects of melatonin on wound healing has been reached since. Bulbuller et al. reported that exogenous melatonin decreased collagen synthesis and epithelium proliferation, and had negative effects on wound healing in both normal and pinealectomized rats.[31] Similarly, Ozdogan et al. found no beneficial effect of exogenous melatonin on colonic anastomosis.[30] On the other hand, Ozen et al. reported that melatonin had a dose-independent positive effect on wound healing of colonic anastomosis in the presence of peritonitis. The authors found significantly higher burst pressure and glutathione levels in rats treated with a high dose of melatonin. In addition, malondialdehyde, blood TNF-α, and IL-6 levels were significantly low in the same group.[32] Mechanisms associated with melatonin that may accelerate wound healing were presently investigated. One mechanism was TGF-β-associated collagen synthesis. Melatonin has been shown to induce production of TGF-β,[4] which plays a significant role in promoting collagen synthesis and healing the colon.[33] In the present study, TGF-β levels were higher in treated rats, corresponding to improved colonic healing. The 320

present findings regarding the effect of melatonin on angiogenesis support those of previous studies. Melatonin increases the number of vessels in wounded tissue.[4] Status of angiogenesis was investigated using CD34 expression. CD34 is a transmembrane glycoprotein that is primarily present in the endothelial cells. Detection of this molecule facilitates identification of blood vessels and endothelial cells in tissues adjacent to the wound site.[34] A steady increase in CD34 expression was presently found in the treatment group. We believe that these high CD34 levels confirm increased angiogenesis and better anastomotic healing in melatonin-treated rats. In conclusion, the present study demonstrated the protective effects of melatonin on anastomotic healing during sepsis. Increased TGF-β levels and CD34 expression were detected in the group treated with melatonin, positively affecting collagen synthesis and angiogenesis. Moreover, in the early period, IL10 levels were significantly higher and CRP levels were significantly lower in treated rats, confirming the anti-inflammatory property of melatonin in the treatment of sepsis. Further studies in which a variety of doses are administered by various application routes are warranted. Conflict of interest: None declared.

REFERENCES 1. Nursal TZ, Anarat R, Bircan S, Yildirim S, Tarim A, Haberal M. The effect of tissue adhesive, octyl-cyanoacrylate, on the healing of experimental high-risk and normal colonic anastomoses. Am J Surg 2004;187:28–32. 2. Peitzman AB, Harbrecht BG, Billiar TR. Shock. In: Brunicardi FC, Andersen DK, Biliar TR, et al. editors. Schwartz’s, Principles of Surgery. 8th ed. New York: McGraw Hill Company; 2005. p. 85–107. 3. Dunn DL, Beilman GJ. Surgical infections. In: Brunicardi FC, Andersen DK, Biliar TR, et al. editors. Schwartz’s, Principles of Surgery. 8th ed. New York: McGraw Hill Company; 2005. p. 109–27. 4. Soybir G, Topuzlu C, Odabaş O, Dolay K, Bilir A, Köksoy F. The effects of melatonin on angiogenesis and wound healing. Surg Today 2003;33:896–901. 5. Baldwin AS Jr, Sharp PA. Two transcription factors, NF-kappa B and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter. Proc Natl Acad Sci U S A 1988;85:723–7. 6. Schreck R, Baeuerle PA. NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene. Mol Cell Biol 1990;10:1281–6. 7. Böhnlein E, Lowenthal JW, Siekevitz M, Ballard DW, Franza BR, Greene WC. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Cell 1988;53:827–36. 8. De Filippis D, Iuvone T, Esposito G, Steardo L, Arnold GH, Paul AP, et al. Melatonin reverses lipopolysaccharide-induced gastro-intestinal motility disturbances through the inhibition of oxidative stress. J Pineal Res 2008;44:45–51. 9. Celinski K, Konturek PC, Konturek SJ, Slomka M, Cichoz-Lach H, Brzozowski T, et al. Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans. J Physiol Pharmacol 2011;62:521–6. 10. Sahib AS, Al-Jawad FH, Alkaisy AA. Effect of antioxidants on the incidence of wound infection in burn patients. Ann Burns Fire Disasters 2010;23:199–205.

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Ersoy et al. Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model 11. Fujimura N, Sumita S, Narimatsu E, Nakayama Y, Shitinohe Y, Namiki A. Effects of isoproterenol on diaphragmatic contractility in septic peritonitis. Am J Respir Crit Care Med 2000;161(2 Pt 1):440–6. 12. Paskaloğlu K, Sener G, Kapucu C, Ayanoğlu-Dülger G. Melatonin treatment protects against sepsis-induced functional and biochemical changes in rat ileum and urinary bladder. Life Sci 2004;74:1093–104. 13. Yamaner S, Buğra D, Müslümanoğlu M, Bulut T, Cubukçu O, Ademoğlu E. Effects of octreotide on healing of intestinal anastomosis following small bowel obstruction in rats. Dis Colon Rectum 1995;38:308–12. 14. Woessner JF Jr. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 1961;93:440–7. 15. Nursal TZ, Bal N, Anarat R, Colakoglu T, Noyan T, Moray G, et al. Effects of a static magnetic field on wound healing: results in experimental rat colon anastomoses. Am J Surg 2006;192:76–81. 16. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981;29:577–80. 17. McCarty KS Jr, Miller LS, Cox EB, Konrath J, McCarty KS Sr. Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 1985;109:716–21. 18. Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 2000;7:444–58. 19. Sener G, Toklu H, Kapucu C, Ercan F, Erkanli G, Kaçmaz A, et al. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg Today 2005;35:52–9. 20. Wu CC, Chiao CW, Hsiao G, Chen A, Yen MH. Melatonin prevents endotoxin-induced circulatory failure in rats. J Pineal Res 2001;30:147–56. 21. Pugazhenthi K, Kapoor M, Clarkson AN, Hall I, Appleton I. Melatonin accelerates the process of wound repair in full-thickness incisional wounds. J Pineal Res 2008;44(4):387–96. 22. Li JH, Yu JP, Yu HG, Xu XM, Yu LL, Liu J, et al. Melatonin reduces inflammatory injury through inhibiting NF-kappaB activation in rats with

colitis. Mediators Inflamm. 2005;2005:185–93. 23. Platzer C, Meisel C, Vogt K, Platzer M, Volk HD. Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int Immunol 1995;7:517–23. 24. Barsig J, Küsters S, Vogt K, Volk HD, Tiegs G, Wendel A. Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor necrosis factor-alpha. Eur J Immunol 1995;25:2888–93. 25. Volk HD, Reinke P, Krausch D, Zuckermann H, Asadullah K, Müller JM, et al. Monocyte deactivation--rationale for a new therapeutic strategy in sepsis. Intensive Care Med 1996;22 Suppl 4:474–81. 26. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003;111:1805–12. 27. Millan M, García-Granero E, Flor B, García-Botello S, Lledo S. Early prediction of anastomotic leak in colorectal cancer surgery by intramucosal pH. Dis Colon Rectum 2006;49:595–601. 28. Yentis SM, Soni N, Sheldon J. C-reactive protein as an indicator of resolution of sepsis in the intensive care unit. Intensive Care Med 1995;21:602–5. 29. Claeys R, Vinken S, Spapen H, ver Elst K, Decochez K, Huyghens L, et al. Plasma procalcitonin and C-reactive protein in acute septic shock: clinical and biological correlates. Crit Care Med 2002;30:757–62. 30. Ozdogan M, Oruk I, Renda N, Kaynaroglu V, Baykal A. The effect of exogenous melatonin on experimental colonic anastomosis. Acta Chir Belg 2005;105:302–5. 31. Bulbuller N, Dogru O, Yekeler H, Cetinkaya Z, Ilhan N, Kirkil C. Effect of melatonin on wound healing in normal and pinealectomized rats. J Surg Res 2005;123:3–7. 32. Ozen IO, Ekingen G, Taşlipinar MY, Bukan N, Demiroğullari B, Karabulut R, et al. Effect of melatonin on healing of colonic anastomosis in a rat model of peritonitis. Eur Surg Res 2007;39:122–7. 33. Buckmire MA, Parquet G, Greenway S, Rolandelli RH. Temporal expression of TGF-beta1, EGF, and PDGF-BB in a model of colonic wound healing. J Surg Res 1998;80:52–7. 34. Lu C, Marcucio R, Miclau T. Assessing angiogenesis during fracture healing. Iowa Orthop J 2006;26:17–26.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel sepsis modelinde melatoninin sitokin salınımı ve kolonik anastomoz iyileşmesi üzerine etkileri Dr. Ömer Faik Ersoy,1 Dr. Namık Özkan,1 Dr. Zeki Özsoy,1 Dr. Hüseyin Ayhan Kayaoğlu,1 Dr. Erdinç Yenidoğan,1 Dr. Alper Çelik,1 Dr. Aziz Fikret Özuğurlu,2 Dr. Ebru Arabacı Çakır,3 Dr. Neşe Lortlar4 Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tokat Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Tokat 3 Atatürk Eğitim ve Araştırma Hastanesi, Patoloji Kliniği, Ankara 4Gazi Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Ankara 1 2

AMAÇ: Deneysel sepsis modelinde erken dönem melatonin uygulamasının anastomoz yara iyileşmesi ve enflamasyon üzerine olan etkilerini göstermeyi amaçladık. GEREÇ VE YÖNTEM: Altmış Wistar-Albino sıçan iki gruba ayrıldı. Melatonin ve kontrol gruplarına çekal ligasyon ve puncture ile kolonik rezeksiyon ve anastomoz yapıldı. Her iki gruptan 10’ar sıçana 16. saat, üçüncü ve yedinci günlerde relaparotomi yapıldı. Erken dönem sepsiste melatonin tedavisinin etkilerini incelemek amacıyla interlökin-6, interlökin-10, interferon-gama, C-reaktif protein düzeyleri, patlama basınçları, anastomotik segmentlerdeki kollajen hidroksiprolin içeriği, histopatolojik iyileşme düzeyleri ve CD34 ve “transforming growth factor beta” immünhistokimyasal düzeyleri değerlendirildi. BULGULAR: Tedavi grubunda interlökin-6 ve interferon-gama düzeylerinin ameliyat sonrası 16. saatte anlamlı olarak azaldığı, üçüncü ve yedinci günlerde ise artmış olduğu bulundu. İnterlökin-10 düzeyleri ise kontrol grubunda ameliyat sonrası 16. saatte anlamlı olarak artmışken, üçüncü ve yedinci günlerde düşük bulundu (p<0.001). Aynı zamanda tedavi grubunda kapiller permeabilite, fibroblast proliferasyonu ve kollajen depositleri anlamlı olarak yüksek bulundu (p<0.001). CD34 ekspresyonu tedavi grubunda ameliyat sonrası yedinci günde anlamlı olarak yüksek bulundu (p=0.005). TARTIŞMA: Sıçan modelinde erken sepsis döneminde melatonin uygulamasının kolonik anastomoz iyileşmesini anlamlı olarak artırdığını düşünüyoruz. Anahtar sözcükler: Anastomosis; colon; melatonin; sepsis. Ulus Travma Acil Cerrahi Derg 2016;22(4):315–321

doi: 10.5505/tjtes.2016.49465

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321

EXPERIMENTAL STUDY

Endogenous erythropoietin level and effects of exogenous erythropoietin in a rat model of blunt chest trauma-induced pulmonary contusion Vedat Bakan, M.D.,1 Ergül Belge Kurutaş, M.D.,2 Harun Çıralık, M.D.,3 Mustafa Gül, M.D.,4 Ahmet Çelik, M.D.2 1

Department of Pediatric Surgery, Esenler Women and Children Diseases Hospital, İstanbul-Turkey

Department of Biochemistry, Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

Department of Pathology, Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

Department of Microbiology, Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

ABSTRACT BACKGROUND: The present objective was to investigate endogen erythropoietin (EPO) level and relationship to oxidative stress within the first 24 hours of blunt chest trauma-induced pulmo-nary contusion (PCn) in a rat model. METHODS: Thirty-five rats were divided into 3 groups. In the baseline control group (BC, n=7), rats were uninjured and untreated. In the positive control group (PC, n=21) rats were injured but untreated. In the EPO-24 group (n=7), rats were injured and a single dose of intra-peritoneal EPO (5000 IU/kg) was administered immediately after lung injury. The PC group was divided into 3 subgroups: PC-6 (n=7), PC-12 (n=7), and PC-24 (n=7). The BC group was subjected to thoracotomy, and the right lung was harvested. The PC subgroups were eu-thanized at 6, 12, and 24 hours after injury, respectively. The EPO-24 group was euthanized at the 24th hour after injury. Lung samples were obtained, levels of malondialdehyde (MDA) and EPO were analyzed, and activities of superoxide dismutase (SOD) and catalase (CAT) were then measured in homogenized lung tissue samples. Histologic damage to lung tissue in the BC group, the EPO24 group, and PC subgroup euthanized at the 24th hour after injury were scored by a single pathologist blinded to group assignation. RESULTS: Mean MDA levels, as well as SOD and CAT activities, of the BC and EPO-24 groups were significantly lower than those of the PC group (p<0.005). Mean EPO concentra-tion of the PC group was significantly higher than that of the BC group (p<0.005). Lung tis-sue damage scores measured at 24 hours after injury were significantly lower in the EPO-24 group than in the PC group (p<0.005). CONCLUSION: In the present PCn rat model, EPO concentrations, as well as SOD and CAT levels, were high in lung tissue, when measured at 24 hours after PCn. When administered early after chest trauma, EPO significantly attenuated oxidative damage and tissue damage in the early phase, as assessed by biochemical markers and histologic scoring. Keywords: Contusion; erythropoietin; lung injury; oxidative stress.

INTRODUCTION Pulmonary contusion (PCn) is the result of kinetic energy transmitted to the pulmonary pa-renchyma, and is defined Address for correspondence: Vedat Bakan, M.D. Esenler Kadın Doğum ve Çocuk Hastalıkları Hastanesi, Çocuk Cerrahisi Kliniği, Havaalanı Mahallesi, Taşocağı Cad., No: 19, Esenler, İstanbul, Turkey Tel: +90 212 - 440 39 00 E-mail: vbakan@gmail.com Qucik Response Code

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as pulmonary parenchymal damage caused by chest trauma in the absence of associated pulmonary laceration. PCn frequently occurs following chest injury, particularly in pediatric patients. Injury to lung tissue results in hemorrhage, edema, inflam-mation, and alveolar collapse.[1,2] However, the exact mechanism of tissue injury has yet to be understood. A variety of pathophysiological alterations are present in cases of PCn, including inflammation, increased alveolocapillary permeability, pulmonary edema, increased intrap-ulmonary shunting, and loss of compliance, resulting in alveolar collapse, ventilation-perfusion mismatch, and hypoxemia.[2–4] In addition, PCn may be the result of oxidative stress and progressive inflammatory response. Reactive oxygen species (ROS) released by both leukocyte and macrophages after blunt chest trauma contribute to tissue damage. Although Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Bakan et al. Epo level in a rat model of pulmonary contusion

antioxidants have been widely tested as treat-ment for blunt chest trauma-related PCn, no standard pharmacological therapy yet exists.[3–6] Erythropoietin (EPO) is a hypoxia-inducible hematopoietic growth factor with antiapoptotic, antioxidant, anti-inflammatory, angiogenic, and neuroprotective effects. Hypoxia is the main stimulus for EPO production; in fact, EPO synthesis may increase 50–100-fold in severely hypoxic conditions.[5,6] EPO is induced via hypoxia-inducible factors such as HIF-1. Hypoxic preconditioning and non-hypoxic inflammatory mediators, including ROS, have been found to increase levels of HIF-1.[7,8] EPO has also been found to attenuate ischemia/reperfusion (I/R)-induced lung injury,[9] as well as tracheobronchial and pulmonary type II epithelial in-jury following traumatic brain injury.[3] In light of the results mentioned above, the present aim was to determine effects of EPO on lung tissue following blunt chest injury-induced PCn in a rat model.

MATERIALS AND METHODS Animals Following approval from the Ethics Committee on Animal Research of the present medical faculty, 35 male Sprague-Dawley rats, weighing 300–330 g each were selected and acclimatized for 10 days in the animal laboratory of the research center, receiving a standard diet and water ad libitum.

Blunt Chest Trauma PCn was induced by method of Raghavendran et al.[10] A hollow, 300-g cylindrical weight encased in a vertical stainless steel tube was dropped from 40 cm, positioned on a Lexon plat-form resting on the rat’s chest. The platform was suspended on Teflon guides, in order to min-imize friction and facilitate energy transfer to the animal. The platform was attached to a plas-tic protective shield in direct contact with the lateral aspect of the rat. This precordial shield was designed to protect the heart from contusion, directing impact energy to the lateral sec-tions of the chest. Impact energy, E (in joules) was calculated using the equation E=mgh, in which m signifies mass of the cylindrical weight (0.3 kg), g signifies gravitational accelera-tion (9.8 m/s2), and h signifies height of the weight above the Lexon platform (0.4 m). Thus, total energy transferred to the chest wall of the rat was 1.17 J.

Experimental Design Rats were divided into 3 groups. The baseline control group (BC, n=7) was uninjured and un-treated. The positive control group (PC, n=21) was injured but untreated, and the EPO-24 group (n=7) was injured and administered EPO. The PC group was divided into 3 subgroups: PC-6 (n=7), PC-12 (n=7), and PC-24 (n=7). Rats were anesthetized with 60 mg/kg of intraperitoneal ketamine hydrochloride (Ketalar; Eczacıbaşı AŞ, İstanbul, Turkey). Blunt chest trauma was administered. ImUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

mediately after the trauma, EPO-24 rats were given a single dose of Eprex intraperitoneal EPO (5000 U/kg; Janssen-Cilag AG, Sihlbruggstrasse, Switzerland). Analgesia was provided by morphine sulphate (0.05 mg/kg) intraperitoneally administered. Following the procedure, all rats were transferred to their cages. The PC-6, PC-12, or PC-24 groups were euthanized by decapitation 6, 12, or 24 hours after chest trauma, respectively. The BC and EPO-24 groups were euthanized by decapitation 24 hours after chest trauma. The right lung was harvested from rats in the BC, PC, and EPO-24 groups. The upper lobes of rats in the BC and EPO-24 groups, as well as those in the PC-24 subgroup were fixed in 10% formaldehyde for histopathological examination. The middle and lower lobes were stored at -8°C until biochemical and EPO assays were performed.

Biochemical Analysis Levels of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and cata-lase (CAT) were measured in the following fashion. Tissue samples were homogenized with 3 volumes of ice-cold 1.15% potassium chloride. Activities of antioxidant enzymes (CAT, SOD), and MDA levels were measured in the supernatant obtained after centrifugation at 14000 rpm. SOD activity was measured in the tissue samples according to the method de-scribed by Fridovich.[11] This method employs xanthine and xanthine oxidase to generate superoxide radicals, which react with p-iodonitrotetrazolium violet (INT) to form a red form-azan dye measured at 505 nm. The assay medium consisted of 0.01 M phosphate buffer, CAPS (3-cyclohexylamino-1-propane sulfonic acid) buffer solution (50 mM CAPS, 0.94 mM EDTA, saturated NaOH) at a pH of 10.2, solution of substrate (0.05 mM xanthine, 0.025 mM INT), and 80 UL xanthine oxidase. SOD activity was expressed as U/mg protein. CAT activity was determined by measuring the decrease in hydrogen peroxide concentration at 230 nm by the method of Beutler.[12] The assay medium consisted of 1-M Tris hydrochlo-ride, 5-mM buffer solution (pH 8.0), 10 mM H2O2, and the tissue sample, to make a final vol-ume of 1.0 mL. CAT activity was expressed as U/mg protein. Tissue sample protein concen-tration was measured with a spectrophotometer by the method of Lowry.[13] MDA levels in tissue samples were measured using the 2-thiobarbituric acid (TBA) test.[14] The reaction mixture contained a 0.1-mL sample, 0.2 mL of 8.1% sodium dodecyl sulphate, 1.5 mL of 20% acetic acid, and 1.5 mL of an 0.8% aqueous solution of TBA. The pH of the mixture was adjusted to 3.5, and the volume was increased to 4.0 mL, by means of distilled water, and 5.0 mL of n-butanol and pyridine mixture (15:1; v/v) was then added. The mixture was shaken vigorously. After centrifugation at 4000 rpm for 10 min, absorbance of the organic layer was 532 nm.

Measurement of Tissue EPO Levels Tissue EPO concentrations were measured with a commer323

Bakan et al. Epo level in a rat model of pulmonary contusion

Table 1. Biochemical parameters and tissue damage scores in groups (mean±SD) Parameters Groups

BC (baseline PC (positive control, n=21) control, n=7)

PC-6 (n=7)

PC-12 (n=7)

EPO-24 (erythropoietin treated, n=7)

PC-24 (n=7)

MDA (nmol/mg protein)

4.5±1.8

32.3±5.8a

CAT (U/mg protein)

32.8±5.7

75.4±22.7 71.5±18.3a 62.5±19.5a 35.2±15.1

SOD (U/mg protein)

12.5±1.6b 13.0±1.5 18.4±1.6a 21.5±5.6a 12.4±1.6

Tissue erythropoietin (ng/mL)

8.4±5.9b 241.2±46.1 240.1±40.1 239.1±58.2

Tissue damage score

0.00±0.00

33.4±5.3a 38.4±13.4a 5.8±1.6

302.0±51.5

10.5±2.1 5.1±1.3 c

MDA: Malondialdehyde; CAT: Catalase; SOD: Superoxide dismutase. Groups were baseline control = uninjured and untreated, positive control = injured but untreated, erythropoietin-treated = injured and given a single dose of IP erythropoietin just after lung injury. All rats of EPO-24 group were killed at hour 24 after chest trauma. Rats of PC-6, PC-12, and PC-24 groups were killed at hour 6, 12, and 24 after chest trauma, respectively. a: p<0.005 vs baseline control and erythropoietin treated groups. b: p<0.005 vs positive control and erythropoietin treated groups. c: p<0.005 vs erythropoietin treated group.

cial kit using the ELISA method (Rat EPO ELISA kit, Cusabio Biotech Co. Ltd., Wuhan Hubei, China). Tissue homogenates were prepared as follows: 100 mg of tissue was rinsed with 1x phosphate buffered solution (PBS), and was homogenized in 1 mL of 1xPBS, then stored overnight at –20°C. After 2 freeze-thaw cycles were performed to break cell membranes, homogenates were centrifuged for 5 minutes at 5000 rpm. The supernate was immediately removed then tested.

Histopathological Evaluation Tissue samples were fixed in 10% neutral buffered formalin solution and embedded in paraf-fin. At least 8 tissue sections of 5-μm thickness were obtained, then stained with haematoxy-lin–eosin and scored by a single pathologist blinded to group distribution. Each specimen was scored for congestion (vascular dilation), hemorrhage, interstitial edema, and alveolar col-lapse on a scale from 0–3, in which 0 signified absence of pathology (<5% of maximum pa-thology), 1 signified mild (5-10% of maximum pathology), 2 signified moderate (11– 20% of maximum pathology), and 3 signified severe pathology (>21% of maximum pathology). The specimen was scored for inflammation as follows: 0 signified no extravascular leukocytes, 1 signified <10 leukocytes, 2 signified 10–45 leukocytes, and 3 signified >45 leukocytes. Total tissue damage was calculated using the scoring system described above.[15]

RESULTS Biochemical Findings Test protocol was successfully implemented in all animals. Lung tissue MDA levels, SOD and CAT activities, EPO concentrations, and total tissue damage scores are listed in Table 1. All biochemical parameters were significantly different between the PC and EPO groups (p<0.005). MDA levels, and CAT and SOD activities were significantly lower in the BC and EPO groups, compared to the PC group (p<0.005). MDA levels and EPO concentrations were significantly higher in the PC-6, PC-12, and PC-24 subgroups, compared to the BC group (p<0.005; Fig. 1). MDA levels in the EPO group were similar to those of the BC group, sug-gesting that MDA levels returned to normal range (Table 1, Fig. 1).

Histopathological Findings Congestion, edema, and alveolar collapse were more prominent in the PC-24 subgroup spec-imens, compared to the BC and EPO-24 group specimens. Total tissue damage scores corre-lated with MDA levels. Total lung tissue damage score of the EPO-24 group was lower than that of the PC-24 group (p<0.005); they were generally grade 0 and 1 in the EPO-24; grade 1 and 2 in the PC-24 group. Lungs from the BC group were normal in histopathological appear-ance (Fig. 2).

Statistical Analysis

DISCUSSION

Individual group biochemical parameters were checked for normalcy of distribution prior to statistical analysis using the Shapiro-Wilk test. The Kruskal-Wallis test was used for nonnormally distributed variables, and Mann–Whitney U test was performed on biochemical data to examine differences among groups. Tissue damage scores were compared using the Mann–Whitney U test. Data were expressed as mean±SD. Results with p<0.005 were considered sta-tistically significant.

Results of present study demonstrate that blunt chest trauma caused oxidative stress evi-denced by biochemical changes. MDA levels were approximately 8 times higher in untreated traumatized rats, compared to non-traumatized and EPOtreated rats. EPO administration also resulted in lower levels of MDA, a marker of hypoxic tissue injury, compared to traumatized rats not administered EPO. Similar to the present results, Türüt et al.[15] and Basaran et al.[16] found significantly

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Bakan et al. Epo level in a rat model of pulmonary contusion

ng/mL

125

-2 4 O

-2 4 PC

-6

-1 2

-2 4

Group

-2 4 O

-2 4 PC

-6

-1 2 PC

Group

25 0 PC

-2 4 O

150

Group

-2 4

0 -6

-1 2

175

100

200

-2 4

†

225

†

250

†

275

Lung tissue erythropoietin concentration

300

-1 2

units/mg protein

325

-6

Lung tissue SOD activity

units/mg protein

Lung tissue CAT activity

nmol/mg protein

Lung tissue MDA level

Figure 1. Levels of malondialdehyde and erythropoietin, as well as activity of superoxide dismutase and catalase in rat lung tissue samples among groups. Groups were baseline control: uninjured and untreated; positive control: injured but untreated; and erythropoietin-treated: injured and administered a single dose of intraperitoneal erythro-poietin immediately after lung injury. PC-6, PC-12, and PC-24 were subgroups of the positive control group. *p<0.005 vs baseline control and erythropoietin-treated groups. †p<0.005 vs baseline control group.

(a)

(b)

(c)

Figure 2. Rat lung histological specimens (all hematoxylin and eosin, x100). (a) Normal lung histology in a baseline control rat (no injury, no treatment). (b) Severe tissue inflammation in a positive control rat (injured, no treatment). (c) Mild tissue inflammation in an injured rat treated with erythropoietin.

higher MDA levels in traumatic lung contusion samples, as well as in lung samples following acute lung injury induced by sodium taurodeoxycholate (causing acute necrotizing pancreatitis). Increased EPO concentration in lung tissues was presently ob-served in the first 24 hours after PCn. Because EPO has anti-inflammatory and antioxidant effects,[17–20] levels were analyzed during the early phase of blunt chest trauma. It was de-termined that EPO administration attenuated oxidative stress and inflammation, as evidenced by biochemical and histological parameters. Presently administered was epoetin alfa, a 165 amino acid glycoprotein manufactured by recombinant DNA technology, which has the same biological effect as endogenous human EPO. It has a molecular weight of 30400 Da and is produced by mammalian cells into which the human EPO gene has been introduced.[5,6] The primary present aim was to determine the EPO level in lung tissue and its relationship with oxidative stress in the first 24 hours of blunt chest trauma— the most critical peUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

riod, in terms of morbidity and mortality. For these reasons, EPO concentrations were measured at 6, 12, and 24 hours of blunt chest trauma. To our knowledge, EPO levels have never before been reported in cases of blunt chest trauma, either in animal or human experimental models. It was presently determined that EPO concentrations were elevated in lung tissue of rats sub-jected to blunt chest trauma-induced PCn. Furthermore, it was found that EPO concentrations, as well as antioxidant enzyme (including SOD and CAT) levels, were increased, compared to controls. EPO exerts its antioxidative effects either directly as a potent free-radical scavenger by the scavenging actions of sugar moieties, or indirectly by increasing the activities of antioxidant enzymes such as SOD, glutathione peroxidase, and CAT.[9,21] Reduced arterial oxygen as-sociated with anemia or hypoxia is the predominant stimulus for EPO production, primarily in the kidneys. On the other hand, EPO is also synthesized in organs such as the liver, spleen, lung, bone marrow, and brain. [5,6] In the present preliminary study, only EPO concentrations in lung tissue were measured, as serum levels could have been affected by other sources of EPO. The present primary limitations were lack of vital signs and oxygenation status measurements. The present study was preliminary, including an evaluation of EPO levels in dam-aged lung tissue, as well as the effect of endogenous EPO in the first 24 hours of lung injury; the present results comprise only preliminary research. Further studies, with similar blunt chest trauma models, are being planned, and with similar parameters, including dosage and timing of administration. It is hoped that all limitations will be addressed in future studies. Increase in antioxidant enzyme activities, such as SOD and CAT, may indicate failure to compensate for oxidative stress. [18,22] In addition, ROS contributes to intensified synthesis of antioxidant enzymes in tissues, the elevated activity of which may be an adaptive response to oxidative stress.[23] 325

Bakan et al. Epo level in a rat model of pulmonary contusion

Expression of CAT has been reported in alveolar type II cells and macrophages.[18] Increase in CAT activity during hypoxia indicates presence of oxidative stress, and may be an adaptive response aimed to protect mitochondria from elevated levels of H2O2.[18,24,25] CAT is an important intracellular antioxidant enzyme, detoxifying H2O2 to oxygen and water. A significant increase in CAT production in the PC group was presumably the result of H2O2 generation in response to hypoxia. SOD plays an important role in catalyz-ing the conversion of superoxide to H2O2 and O2, which are then metabolized to water by CAT or other peroxidases. This enzyme has 3 isoforms, and all SODs are highly expressed in the lung tissue, vessels, and airways. However, extracellular SOD activity is reportedly much higher in the lung.[18] Organisms can defend themselves against oxidative stress by increas-ing SOD activity as a protective mechanism.[22,26] In the present study, CAT and SOD ac-tivity levels in EPO-treated animals were close to those of the BC group, which underwent no trauma. In the present EPO-treated group, the restoration of antioxidant enzyme activity confirms the critical role of EPO in regulating oxidative stress due to blunt chest trauma, and points to its property as a direct, potent free-radical scavenger. Production and secretion of EPO are regu-lated according to the supply of oxygen to the tissues. Hypoxia is the main stimulus for EPO production; in fact, EPO synthesis may increase 50-fold in severely hypoxic conditions.[5–8] EPO production is induced via hypoxia-inducible factors such as HIF-1, a transcription factor that plays a central role in cellular and systemic homeostatic responses to hypoxia.[5,6,19,20] Hypoxic preconditioning and non-hypoxic inflammatory mediators, including ROS, were found to increase levels of HIF-1.[5–8] Also, hypoxia induces monocyte chemoattractant pro-tein-1 (MCP-1) release from alveolar macrophages. MCP-1 induces chemotaxis of alveolar macrophages and mast cells.[2,18] HIF-1 is involved in transcriptional activation of MCP-1 expression stimulated by hypoxia in humans; MCP-1 is an HIF-1 target gene. Increases in HIF-1 and MCP-1 were determined in lung homogenates of rats subjected to hypoxia (10% O2).[9] One of the primary present findings was that, for the first time, EPO concentrations in lung tissue following blunt chest trauma were much higher, compared to tissue of non-traumatized rats. Lung tissue is a major site of ROS production. Cells involved also include alveolar macro-phages, neutrophils, mast cells, type II pneumocytes, endothelial cells, smooth muscle cells, and lung fibroblasts.[25,26–30] In inflammatory lung conditions, H2O2 is primarily pro-duced in alveolar macrophages and neutrophils.[8,29] Alveolar macrophages are directly acti-vated by low oxygen levels. For example, lowering partial pressure of oxygen from 100 to 70 ToR induces a transitory release of H2O2 into the supernatant of alveolar macrophage cul-tures. [29] Protective properties of EPO have been demonstrated in models of ischemic and inflammatory injury in neuronal, vascular, cardiac, and intestinal tissues.[5,6] However, little is known regarding expression of EPO in pulmonary tissues, or 326

the potential role of EPO in pathological processes of the lung. Recently, EPO and its receptor were found to be expressed in respiratory epithelium.[26] EPO was also found to protect epithelial cells from neutrophil-mediated apoptosis agents.[25] Thus, EPO is thought to have anti-apoptotic and cytoprotec-tive properties in the respiratory epithelium.[9,25] Pretreatment with EPO appears to attenuate I/R-induced lung injury in rats.[9] This ability is at least partially due to EPO’s inhibition of the accumulation of polymorphonuclear neutrophils in lung tissue.[9] In the present study, CAT activities in the EPO-treated group were similar to those of the BC group, suggesting a lack of polymorphonuclear neutrophil accumulation and/or lack of excessive intracellular H2O2 accumulation. At 24 hours after contusion in the present study, alveolar edema/congestion and leukocyte infiltration in the lung tissue sig-nificantly increased, but subsided following administration of EPO. EPO most likely acts through a variety of pathways to protect lung tissue against damage from inflammation. PCn is associated with leukocyte-mediated secondary inflammatory response leading to capil-lary leak, alveolar oedema, and protein extravasation. In addition, histopathological changes are related to severity of the injury. Leukocyte infiltration in the alveolar space and atelectasis have been observed at 24 hours post-contusion.[10,15] In the present study, congestion, hem-orrhage, inflammation, interstitial edema, and alveolar collapse were scored. Total tissue damage score demonstrated significant decrease with the use of EPO. This and other results emphasize the protective effect of EPO on the lungs by reducing inflammation, likely related to anti-inflammatory potential. In conclusion, endogenous lung parenchyma levels of EPO are elevated following PCn. Ex-ogenous EPO administered after PCn reduced oxidative damage, evidenced histopathological-ly and biochemically. Antioxidant and cytoprotective treatment with compounds such as EPO may contribute to the health of lung tissues following PCn. Further studies of dosage and tim-ing should be performed to clarify underlying mechanisms and maximize the benefit of the protective effect of EPO on lung parenchyma following traumatic injury. Conflict of interest: None declared.

REFERENCES 1. Pulmonary contusion in children. http://www.uptodate.com/contents/ pulmonary-contusion-in-children. 2. Hoth JJ, Stitzel JD, Gayzik FS, Brownlee NA, Miller PR, Yoza BK, et al. The pathogenesis of pulmonary contusion: an open chest model in the rat. J Trauma 2006;61:32–45. 3. Yildirim E, Ozisik K, Solaroglu I, Kaptanoglu E, Beskonakli E, Sargon MF, et al. Protective effect of erythropoietin on type II pneumocyte cells after traumatic brain injury in rats. J Trauma 2005;58:1252–8. 4. Tkaczyk J, Vízek M. Oxidative stress in the lung tissue--sources of reactive oxygen species and antioxidant defence. Prague Med Rep 2007;108:105– 14. 5. Jelkmann W. Erythropoietin after a century of research: younger than

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Bakan et al. Epo level in a rat model of pulmonary contusion ever. Eur J Haematol 2007;78:183–205. 6. Brines M, Cerami A. Discovering erythropoietin’s extra-hematopoietic functions: biology and clinical promise. Kidney Int 2006;70:246–50. 7. Jones NM, Bergeron M. Hypoxic preconditioning induces changes in HIF-1 target genes in neonatal rat brain. J Cereb Blood Flow Metab 2001;21:1105–14. 8. Bonello S, Zähringer C, BelAiba RS, Djordjevic T, Hess J, Michiels C, et al. Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site. Arterioscler Thromb Vasc Biol 2007;27:755–61. 9. Wu H, Ren B, Zhu J, Dong G, Xu B, Wang C, et al. Pretreatment with recombined human erythropoietin attenuates ischemia-reperfusion-induced lung injury in rats. Eur J Cardiothorac Surg 2006;29:902–7. 10. Raghavendran K, Davidson BA, Helinski JD, Marschke CJ, Manderscheid P, Woytash JA, et al. A rat model for isolated bilateral lung contusion from blunt chest trauma. Anesth Analg 2005;101:1482–9. 11. Fridovich I. Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol 1983;23:239–57. 12. Beutler E. Red cell metabolism: a manual of biochemical methods. 3rd ed. New York: Grune & Stratton; 1984. 13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75. 14. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8. 15. Türüt H, Ciralik H, Kilinc M, Ozbag D, Imrek SS. Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats. Injury 2009;40:521–7. 16. Basaran UN, Ayvaz S, Aksu B, Karaca T, Cemek M, Karaboga I, et al. Desferrioxamine reduces oxidative stress in the lung contusion. ScientificWorldJournal 2013;2013:376959. 17. Madjdpour C, Jewell UR, Kneller S, Ziegler U, Schwendener R, Booy C, et al. Decreased alveolar oxygen induces lung inflammation. Am J Physiol Lung Cell Mol Physiol 2003;284:360–7. 18. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 2014;20:1126–67. 19. Tabata M, Tarumoto T, Ohmine K, Furukawa Y, Hatake K, Ozawa K, et al. Stimulation of GATA-2 as a mechanism of hydrogen peroxide

suppression in hypoxia-induced erythropoietin gene expression. J Cell Physiol 2001;186:260–7. 20. Chao J, Wood JG, Gonzalez NC. Alveolar macrophages initiate the systemic microvascular inflammatory response to alveolar hypoxia. Respir Physiol Neurobiol 2011;178:439–48. 21. Fandrey J, Frede S, Ehleben W, Porwol T, Acker H, Jelkmann W. Cobalt chloride and desferrioxamine antagonize the inhibition of erythropoietin production by reactive oxygen species. Kidney Int 1997;51(2):492–6. 22. Chattopadhyay S, Sahoo DK, Subudhi U, Chainy GB. Differential expression profiles of antioxidant enzymes and glutathione redox status in hyperthyroid rats: a temporal analysis. Comp Biochem Physiol C Toxicol Pharmacol 2007;146:383–91. 23. Komosinska-Vassev K, Olczyk K, Kucharz EJ, Marcisz C, Winsz-Szczotka K, Kotulska A. Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves’ disease during therapy. Clin Chim Acta 2000;300:107–17. 24. Zelko IN, Folz RJ. Extracellular superoxide dismutase functions as a major repressor of hypoxia-induced erythropoietin gene expression. Endocrinology 2005;146:332–40. 25. MacRedmond R, Singhera GK, Dorscheid DR. Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury. Eur Respir J 2009;33:1403–14. 26. Folz RJ, Guan J, Seldin MF, Oury TD, Enghild JJ, Crapo JD. Mouse extracellular superoxide dismutase: primary structure, tissue-specific gene expression, chromosomal localization, and lung in situ hybridization. Am J Respir Cell Mol Biol 1997;17:393–403. 27. Nakanishi K, Tajima F, Nakamura A, Yagura S, Ookawara T, Yamashita H, et al. Effects of hypobaric hypoxia on antioxidant enzymes in rats. J Physiol 1995;489:869–76. 28. Giles BL, Suliman H, Mamo LB, Piantadosi CA, Oury TD, NozikGrayck E. Prenatal hypoxia decreases lung extracellular superoxide dismutase expression and activity. Am J Physiol Lung Cell Mol Physiol 2002;283:L549–54. 29. van der Vliet A, Cross CE. Oxidants, nitrosants, and the lung. Am J Med 2000;109:398–421. 30. Chao J, Wood JG, Blanco VG, Gonzalez NC. The systemic inflammation of alveolar hypoxia is initiated by alveolar macrophage-borne mediator(s). Am J Respir Cell Mol Biol 2009;41:573–82.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Künt göğüs travmasıyla oluşturulan pulmoner kontüzyon sıçan modelinde eritropoietin düzeyleri ve eksojen eritropoietinin etkileri Dr. Vedat Bakan,1 Dr. Ergül Belge Kurutaş,2 Dr. Harun Çıralık,3 Dr. Mustafa Gül,4 Dr. Ahmet Çelik2 Esenler Kadın Doğum ve Çocuk Hastalıkları Hastanesi, Çocuk Cerrahisi Kliniği, İstanbul Sütçü İmam Üniversitesi Tıp Fakültesi, Biokimya Anabilim Dalı, Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Kahramanmaraş 4 Sütçü İmam Üniversitesi Tıp Fakültesi, Mikrobiyoloji Anabilim Dalı, Kahramanmaraş 1 2 3

AMAÇ: Sıçanlarda oluşturulan künt göğüs travmasına bağlı akciğer kontüzyon modelinde, ilk 24 saat içinde endojen eritropoetin düzeylerinin oksidatif stresle ilişkisi ve ekzojen eritropoietinin etkilerini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Otuz beş sıçan üç gruba ayrıldı: Grup BC (bazal kontrolü, n=7), herhangi bir işlem yapılmadı; Grup PC (pozitif kontrol, n=21), sıçanlarda kontüzyon oluşturuldu fakat tedavi verilmedi; Grup EPO-24 (eritropoietin tedavi, n=7), sıçanlarda kontüzyon oluşturuldu ve künt göğüs travmasından hemen sonra intraperitonal (5000 lU/kg) tek bir doz eritropoietin verildi. Pozitif kontrol grubu her grupta yedişer sıçan olacak şekilde üç alt gruba ayrıldı (PC-6, PC-12, PC-24). PC-6, PC-12, PC-24 grubundaki sıçanlar, künt travmadan 6, 12 ve 24 saat sonra, EPO-24 ve BC grubundaki sıçanlar ise travmadan 24 saat sonra öldürüldü. Akciğer dokusunda malondialdehit (MDA) ve EPO düzeyleri, süperoksit dismutaz (SOD) ve katalaz (CAT) aktiviteleri ölçüldü. BC, PC-24 ve EPO-24 gruplarında histopatolojik incelemeyle total doku hasarı saptandı. BULGULAR: Ortalama MDA düzeyleri, SOD ve CAT aktiviteleri BC ve EPO-24 gruplarında PC grubuna göre düşüktü (p<0.005). PC-6, PC-12 ve PC-24 grubunun ortalama EPO konsantrasyonu BC grubuna göre daha yüksek bulundu (p<0.005). Akciğer doku hasarı skorları EPO-24 grubunda PC-24 grubuna göre daha düşüktü (p<0.005). TARTIŞMA: Eritropoietin konsantrasyonları, SOD ve CAT düzeyleri pulmoner kontüzyon sonrası ilk 24 saatte akciğer dokusunda yüksek olduğu saptandı. Göğüs travması sonrası akut dönemde uygulanan tek doz intraperitoneal eritropoetin (5000 IU/kg), travmanın erken döneminde oksidatif hasarı ve doku zedelenmesini azaltmaktadır. Anahtar sözcükler: Akciğer hasarı; eritropoietin; kontüzyon; oksidatif stres. Ulus Travma Acil Cerrahi Derg 2016;22(4):322–327

doi: 10.5505/tjtes.2015.09483

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ORIGIN A L A R T IC L E

Comparing Pediatric Trauma, Glasgow Coma Scale and Injury Severity scores for mortality prediction in traumatic children Shahrokh Yousefzadeh-Chabok, M.D., Ehsan Kazemnejad-Leili, M.D., Leila Kouchakinejad-Eramsadati, M.D., Marieh Hosseinpour, M.D., Fatemeh Ranjbar, M.D., Reza Malekpouri, M.D., Zahra Mohtasham-Amiri, M.D., MPH Preventive and Social Medicine, Medical Faculty, Guilan Road Trauma Research Center, Guilan University of Medical Sciences, Rasht-Iran

ABSTRACT BACKGROUND: Trauma is a major cause of disability and death among children worldwide, particularly in developed countries. The present aim was to compare efficacies of the Pediatric Trauma score (PTS), the Glasgow Coma Scale score (GCS), and the Injury Severity Score (ISS) in the prediction of mortality in children injured by trauma. METHODS: A total of 588 children admitted to the emergency ward of the Poursina Medical and Educational Center from 2010– 2011 with trauma were included. The PTS, GCS, and ISS were calculated for all patients. Predictive efficacy of these scores was compared using receiver operating characteristic (ROC) curve with 95% confidence interval. RESULTS: Of the patient population, 62.1% were male and 37.9% female, with a mean age of 7.31±3.8 years. Road accident (42.2%) was the most common cause of injury. Overall, 2.4% of participants died. Regarding the prediction of mortality, the best cut-off point for the GCS was ≤8, with 98.4% sensitivity and 92.3% specificity. The same point for the PTS was ≤0.5, with 100% sensitivity and 31% specificity. For the ISS it was ≥16.5, with 92.5% sensitivity and 62% specificity. All variables based on mortality prediction were statistically significant (p<0.0001). CONCLUSION: When compared to the PTS and ISS, the GCS may be a better predictor of mortality in cases of childhood trauma. Key words: Children; Glasgow Coma Scale; Injury Severity Score; Pediatric Trauma Score; trauma.

INTRODUCTION In developed countries, trauma is one of the most significant causes of childhood morbidity, with the potential to lead to disease, long-term disability, or death in the early years of life.[1] Pediatric trauma remains a major health issue in the US, is the primary cause of over 10000 annual child mortalities worldwide, and is the cause of approximately 10% of pediatric hospitalizations. According to data recorded in Iran in 2005, trauma, irrespective of gender, was the second

Address for correspondence: Zahra Mohtasham-Amiri, M.D. Guilan Road Trauma Research Center, Poursina Hospital, Namjoo Street Rasht, Iran Tel: +00981333338373 E-mail: mohtashamaz@yahoo.com Qucik Response Code

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leading cause of mortality[2] and the most common cause of death between the ages of 1 and 14 years.[3] Damage caused by major trauma can be reduced with prompt pre-hospital and in-hospital intervention.[4,5] A quantitative scale has been deemed necessary to assess trauma severity, triage, and outcome in trauma centers.[6–9] These scoring systems have played a vital role in the advancement of trauma care over the past 20 years. However, many emergency physicians are still unfamiliar with these systems.[1] The Pediatric Trauma score (PTS), Glasgow Coma Scale (GCS), and Injury Severity Score (ISS) can be used to evaluate trauma in children.[10] The PTS is easily calculable and can be used by care providers with any level of skill. It is effective in cases of emergency because, in addition to assessing injury severity, it can also be used to identify risk of immediate death if no appropriate treatment is administered in time.[1] The GCS is the scale most commonly used to measure severity of traumatic brain injury, in adults as well as in children, following a modification. [1,11] The pediatric GCS is utilized for pre-verbal children.[1] The ISS is an anatomic score and independent predictor of death following severe trauma, appropriate for patients with Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Yousefzadeh-Chabok et al. Comparing Pediatric Trauma, GSC and Injury Severity scores for mortality prediction in traumatic children

multiple injuries.[1] This scale correlates well with mortality, disability, and hospitalization.[12] Given the importance of scoring systems in recognizing risk in immediate, as well as general, outcome, the present aim was to identify the scale that could be used most quickly and accurately to assess childhood trauma.

MATERIALS AND METHODS The present retrospective study included 588 children with trauma admitted to the emergency ward of Poursina Medical and Educational Center in Rasht (Gilan province) between 2010 and 2011. A checklist was used for data collection

Table 1. Pediatric Glasgow Coma Scale

Pediatric GCS

Eye opening

None

Score value 1

To pain

To voice

Spontaneously

Verbal response

None

Inconsolable, agitated

Inconsistently consolable, moaning

Cries, but is consolable, inappropriate interaction

Smiles, oriented to sounds, follows objects, interacts

Motor response

None

Extension to pain

Flexion to pain

Withdrawal from pain

Localizing pain

Obeys commands

Table 2. Calculation of Pediatric Trauma score Clinical parameter

Parameter category

Weight (kg)

≥20

Score value +2

10–19

<10

–1

Airway

Patent

Maintainable

Unmaintainable –1 Systolic blood pressure

>90

50–89

<50

–1

Central nervous system

Awake

Obtunded or loss of consciousness

Coma or decerebrate

–1

Open wound

None

Minor

–1

Major or penetrating

Skeletal None

Closed fracture

Open or multiple fractures

–1

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from the hospital information system. Necessary information obtained from patient records included demographic characteristics, injury (site and type, mode of transportation to hospital), primary assessment (vital signs), and evaluation of mortality (time and cause of death). Outcome of trauma was defined as death or survival. Patients with incomplete records or previous history of disease (cardiovascular, renal, pulmonary, or cerebral, such as stroke) were excluded. The GCS (in which motor, verbal, and ocular responses are classified from 3–15) was used, according to clinical condition.[13] A score of 3 corresponded to worst outcome (coma or death), 15 corresponded to best outcome (no neurological deficit) (Table 1).

Table 3. Demographic information and mean of scales in 588 cases of childhood trauma Age (yrs), mean (SD)

7.31

3.8

Mean±SD (mid)

Age groups

0–2 years

12.8

3–10 years

386

65.6

11–14 years

127

21.6

Gender Female

365 62.1

Male

223 37.9

Road traffic accident

To calculate PTS, 3 physiological and 3 anatomical conditions were assessed, including body mass index (BMI), condition of access to airways, fracture, level of consciousness, systolic blood pressure, and condition of wounds. Scores range from -6 to +12 (Table 2).[13]

The ISS is derived from the Abbreviated Injury Scale (AIS). The AIS can be used to accurately rank injury severity, and is graded from 1 (minor injury) to 6 (unsurvivable injury). The sum of the square of AIS values higher than 3 (corresponding to the most severely injured regions) is used to calculate ISS.

Falling

234 39.8

Assault

1.7

7.3

Sport

6.6

Other

2.4

Accuracy in the prediction of survival was compared among these scoring systems, and included specificity, sensitivity, and cut-off points, according to receiver operating characteristic (ROC) curve with 95% confidence interval. Statistical analysis was conducted using SPSS software (version 18.0; SPSS Inc., Chicago, IL, USA).

Trauma Score

Passenger

106

44.3

Cyclist

37 14.5

Motor cyclist

Pedestrian

19.6

55 21.6

Mechanism of trauma

Sharp object

GCS

14.39±2.02 (15)

PTS

9.8±1.88 (10)

ISS

6.47±6.07 (4)

SD: Standard deviation; GCS: Glasgow Coma Scale; PTS: Pediatric Trauma Score; ISS: Injury Severity Score.

RESULTS Of the 588 children included, 62.1% were male and 37.9% were female, with a mean age of 7.31±3.8 years, and a range of 3 months to 14 years of age. Road accident (42.2%, n=248) and falling (39.8%, n=234) were the most common causes of injury. The majority of children were car passengers (44.3%). Demographic information and means of scales (ISS, GCS, and PTS) are shown in Table 3. Overall, 92.2% (n=542) of injuries were blunt, and 7.8% (n=48) were penetrating. Areas most commonly damaged were the extremities (92.9%, n=546), followed by the head and neck (27.4%, n=161), and the face (23.3%, n=137). A total of 97.6% (574) of the population survived, while 2.4%[14] died. Mean GCSs were 14.63±1.31 and 4.71± 2.23 in those who survived and those who died, respectively. Mean PTSs were 9.93±1.55 and 3.85±4.12 in those who survived and those who died, respectively. Mean ISSs were 6.26±5.9 and 17.71±4.34 in those who survived and those who died, respectively. Mean differences in GCSs, PTSs, and ISSs between those who survived and those who died were statistically significant (p<0.001) 330

Table 4. Comparison of scoring systems in two groups of children: Those who survived and those who died Score status

Mean±SD

Glasgow Coma Scale Deaad

4.7±2.2

Survived

574

14.6±1.3

Dead

17.7±4.3

Survived

574

6.3±5.9

Dead

3.8±4.1

Survived

562

9.9±1.5

0.0001

Injury Severity Score 0.0001

Pediatric Trauma Score 0.0001

SD: Standard deviation.

(Table 4). ROC area under the curve (AUC) for prediction of mortality was highest for the GCS, compared to the PTS and the ISS (AUC: 0.997; p=0.000) (Fig. 1, Table 5). Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Yousefzadeh-Chabok et al. Comparing Pediatric Trauma, GSC and Injury Severity scores for mortality prediction in traumatic children

Table 5. Efficacy of the PTS, GCS, and ISS in mortality prediction of childhood trauma Scoring Systems

AUC*

Std. Error

CI 95%

PTS

0.949 0.021 0.908–0.991

GCS

0.997 0.002 0.993–1

ISS

0.929 0.018 0.894–0.963

GCS: Glasgow Coma Scale; PTS: Pediatric Trauma Score; ISS: Injury Severity Score. *Area Under Curve.

Table 6. Logistic regression analysis using injury scoring systems Predictor

S.E.

95% C.I for OR

ISS

0.36 0.19 1.43

0.98–2.10

GCS

1.60 0.64 4.97 1.41–17.55

PTS

0.55 0.37 1.74

0.84–3.62

GCS: Glasgow Coma Scale; PTS: Pediatric Trauma Score; ISS: Injury Severity Score.

Desired cut-off was ≤8 for the GCS (sensitivity: 98.4%; specificity: 92.3%), ≤0.5 for the PTS (sensitivity: 100%; specificity: 31%), and ≥16.5 for the ISS (sensitivity: 92.5%; specificity: 62%). Multivariate logistic regression analysis using backward stepwise model (likelihood ratio: probabilities of inclusion and exclusion of variables from the model; entry=0.05, removal=0.1) showed GCS as the only predictor of mortality (p=0.015), so that 1-unit decrease in mortality rate increased mortality risk 4.9 times (95% confidence interval: 1.36–17.5).

Trauma is considered a threat to childhood survival.[14] More than 30% of these deaths can be prevented by quality primary treatment.[15] Quantitative trauma scoring systems are important methods of evaluating and comparing trauma treatment standards.[16] Males comprised the majority of the present population, in accordance with the findings of others.[1,14,17,18] The most common causes of trauma in the present population were road accident, followed by fall. Franze´n Derakhshanfar et al. reported the same findings,[14,18] while Adegoke et al. reported fall to be the most common cause, followed by road accident.[19] While the most common sites of injury were presently found to be the extremities, followed by the head and neck, Letts et al. reported the head as the area most commonly injured.[20] Means of GCS, PTS, and ISS were presently found to be 14.4, 9.8, and 6.5, respectively. These means were 4.7, 3.8, and 17.7, respectively, in children who died. Letts et al. reported a PTS mean of 8.5 overall, and 3.8 in the mortality group. Mean GCS was 11.8 overall, and 3.4 in the mortality group.[20] Bulut et al. reported a mean ISS of 8.7 overall, and 2.5 in the mortality group.[17] The best GCS cut-off point was presently determined as 8, with sensitivity of 98.4% and specificity of 92.3%. Grinkeviciūte et al. found the best GCS cut-off point to be 5, with 79% sensitivity and 67% specificity.[1] The best ISS cut-off point was presently determined as 16.5, with sensitivity of 92.5% and specificity of 62%. Bulut et al. found the best ISS cut-off point to be 22, with sensitivity of 90.5% and specificity of 95.4%.[1] ROC curve analysis indicated that all 3 scoring systems were statistically significant for prediction of mortality, but that GCS was the strongest. In a similar study including children with severe trauma in intensive care, Cantais et al. reported that the same systems had significant association with mortality, though the GCS had the highest predictive ability.[21] Furthermore, in a study in which 11 trauma parameters were compared among children and adults, Otto et al. reported that physical parameters, including the GCS, had higher predictive ability than those that were anatomical, including the PTS and ISS.[22]

0.8

Sensitivity

DISCUSSION

ROC Curve

1.0

0.6

0.4

Source of the Curve Injury Severity Score Glasgow Coma Scale Pediatric Trauma Score Reference Line

0.2

0.0

Although the other parameters (PTS and ISS) were included as predictors in the final model, they were not found to be statistically significant (Table 6).

0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Diagonal segments are produced by ties.

Figure 1. Comparison of the PTS, GCS, and ISS in mortality prediction of pediatric trauma patients.

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Conclusion Researchers, policymakers, and directors of medical centers should take steps toward implementing precise patient evaluation and preventive programs, in order to improve the quality of services and care. The present results indicate that the GCS, PTS, and ISS can be used to predict mortality with statistical significance in child patients with trauma. The GCS had the strongest significance, and implementation of this 331

Yousefzadeh-Chabok et al. Comparing Pediatric Trauma, GSC and Injury Severity scores for mortality prediction in traumatic children

reliable and user-friendly scoring system may positively contribute to timely and proper planning, aid in pre-hospital and in-hospital evaluation and care, and ultimately reduce costs.

Acknowledgment The present study was based on a thesis submitted by the third author to the Gilan University of Medical Sciences. The authors would like to express their gratitude to the Clinical Research Development Unit of the Gilan University of Medical Sciences. We also thank Ms. Fatemeh Javadi for translating the manuscript. Conflict of interest: None declared.

REFERENCES 1. Grinkeviciūte DE, Kevalas R, Saferis V, Matukevicius A, Ragaisis V, Tamasauskas A. Predictive value of scoring system in severe pediatric head injury. Medicina (Kaunas) 2007;43:861–9. 2. Memarzadeh M, Hoseinpour M, Sanjary N, Karimi Z. A study on trauma epidemiology in children referred to Isfahan Alzahra Hospital during 2004-7. KAUMS Journal (FEYZ) 2011;14:488–93. 3. Khodadadi H, Asadpoor M, Zohreh Kermani SH, Ravari A. Frequency of the Accidents in Children Under 15 Years Old Referring to the Emergency Center of Ali Ebn Abitaleb Hospital in Rafsanjan 2000-2001. JRUMS 2006;5:201–8. 4. Sasser s, Varghese M, Kellermann A, Lormand JD. Prehospital trauma care system. World Health OrganizationGeneva. 2005. In: http://www. who.int/violence_injury_prevention/media/news/04_07_2005/en/ [Access on: 2015.02.20]. 5. MacKenzie EJ, Rivara FP, Jurkovich GJ, Nathens AB, Frey KP, Egleston BL, et al. A national evaluation of the effect of trauma-center care on mortality. N Engl J Med 2006;354:366–78. 6. Sharma BR. Triage in trauma-care system: a forensic view. J Clin Forensic Med 2005;12:64–73. 7. Moradi Lakeh M, Tehrani Banihashemi SA, Varasteh Kia GR, Roohipour MR. Comparison of Trauma Scoring Systems for Prediction of

Patients’ Prognosis. RJMS 2002;9:129–37. 8. Chawda MN, Hildebrand F, Pape HC, Giannoudis PV. Predicting outcome after multiple trauma: which scoring system? Injury 2004;35:347–58. 9. Champion HR. Trauma scoring. Scand J Surg 2002;91:12–22. 10. Trabold F, Meyer PG, Blanot S, Carli PA, Orliaguet GA. The prognostic value of transcranial Doppler studies in children with moderate and severe head injury. Intensive Care Med 2004;30:108–12. 11. Ghaffarpasand F, Razmkon A, Dehghankhalili M. Glasgow Coma Scale Score in Pediatric Patients with Traumatic Brain Injury; Limitations and Reliability. Bull Emerg Trauma 2013;1:135–6. 13. Marcin JP, Pollack MM. Triage scoring systems, severity of illness measures, and mortality prediction models in pediatric trauma. Crit Care Med 2002;30(11 Suppl):457–67. 14. Derakhshanfar H, Hatamabadi H, Karimian K, Abdalvand A, Dolatabadi AA, Shahrami A, et al. The prognosis of trauma among children and the factors contributing to it. Health 2012;4:212–5. 15. Ducrocq SC, Meyer PG, Orliaguet GA, Blanot S, Laurent-Vannier A, Renier D, et al. Epidemiology and early predictive factors of mortality and outcome in children with traumatic severe brain injury: experience of a French pediatric trauma center. Pediatr Crit Care Med 2006;7:461–7. 16. Thanapaisal C, Wongkonkitsin N, Seow OT, Rangsrikajee D, Jenwitheesuk K, Phugkhem A, et al. Outcome of in-patient trauma cases: Accident and Emergency Unit, Khon Kaen University. J Med Assoc Thai 2005;88:1540–4. 17. Bulut M, Koksal O, Korkmaz A, Turan M, Ozguc H. Childhood falls: characteristics, outcome, and comparison of the Injury Severity Score and New Injury Severity Score. Emerg Med J 2006;23:40–5. 18. Franzén L, Ortenwall P, Backteman T. Children in Sweden admitted to intensive care after trauma. Injury 2007;38:91–7. 19. Adegoke SA, Oginni LM. Predictors of paediatric injury mortality. SAJCH 2011;5:15–8. 20. Letts M, Davidson D, Lapner P. Multiple trauma in children: predicting outcome and long-term results. Can J Surg 2002;45:126–31. 21. Cantais E, Paut O, Giorgi R, Viard L, Camboulives J. Evaluating the prognosis of multiple, severely traumatized children in the intensive care unit. Intensive Care Med 2001;27:1511–7. 22. Ott R, Krämer R, Martus P, Bussenius-Kammerer M, Carbon R, Rupprecht H. Prognostic value of trauma scores in pediatric patients with multiple injuries. J Trauma 2000;49:729–36.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Travma geçirmiş çocuklarda mortalite öngörüsünde Pediyatrik Travma, Glasgow Koma Ölçeği ve Comparing Pediatric Trauma, Travma Şiddet Derecesi skorlarının karşılaştırması Dr. Shahrokh Yousefzadeh-Chabok, Dr. Ehsan Kazemnejad-Leili, Dr. Leila Kouchakinejad-Eramsadati, Dr. Marieh Hosseinpour, Dr. Fatemeh Ranjbar, Dr. Reza Malekpouri, Dr. Zahra Mohtasham-Amiri Koruyucu ve Sosyal Tıp, Tıp Fakültesi, Guilan Yolu Travma Araştırma Merkezi, Guilan Üniversitesi Sağlık Bilimleri, Rast-İran

AMAÇ: Dünya ölçeğinde özellikle gelişmiş ülkelerdeki çocuklar arasında travma sakatlık ve ölümün önemli bir nedenidir. Burada amaç travma sonucu yaralanmış çocuklarda mortaliteyi öngörmede Pediyatrik Travma skoru (PTS), Glasgow Koma Ölçeği skoru (GKS) ve Travma Şiddet Derecesi skorunun etkililiklerini karşılaştırmaktı. GEREÇ VE YÖNTEM: Poursina Tıp ve Eğitim Merkezi’nin Acil Servisi’ne 2010-2011 yılı arasında toplam 588 travmalı çocuk kabul edilmiştir. Hastaların hepsi için PTS, GCS ve ISS hesaplandı. Alıcı işletim karakteristik (ROC) eğrisi kullanılarak %95 güven aralığıyla bu skorların öngördürücü etkililiği karşılaştırıldı. BULGULAR: Hasta popülasyonunun %62.1’i erkek ve %37.9’u kız çocuklarından ibaretti. Yaş ortalaması 7.31±3.8 yıl idi. Yaralanmanın en sık görülen nedeni trafik kazasıydı (%42.2). Genelde katılımcıların % 2.4’ü ölmüştü. Mortalitenin öngörüsü açısından GKS için en iyi kestirme değeri ≤8 olup %98.4 duyarlılık ve %92.3 özgüllüğe sahipti. PTS için kestirme değer ≤0.5 olup %100 duyarlılık ve %31’lik özgüllüğe sahipti. ISS için bu değer ≥16.5 olup %92.5 duyarlılık ve %62’lik özgüllüğe sahipti. Mortalite öngörüsüne dayalı tüm değişkenler istatistiksel açıdan anlamlıydı (p<0.0001). TARTIŞMA: Çocukluk çağı travma olgularında PTS ve ISS ile karşılaştırıldığında GKS daha iyi bir öngördürücü faktör olabilir. Anahtar sözcükler: Çocuklar; Glasgow Koma Ölçeği; Pediyatrik Travma Skoru; travma; Travma Şiddet Skoru. Ulus Travma Acil Cerrahi Derg 2016;22(4):328–332

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doi: 10.5505/tjtes.2015.83930

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ORIGIN A L A R T IC L E

Evaluation of patients with snakebite who presented to the emergency department: 132 cases Mustafa Şahan, M.D.,1 Veyis Taşın, M.D.,1 Ali Karakuş, M.D.,1 Oguzhan Özcan, M.D.,2 Umut Eryiğit, M.D.,3 Güven Kuvandık, M.D.1 1

Department of Emergency Medicine, Mustafa Kemal University Faculty of Medicine, Hatay-Turkey

Department of Biochemistry, Mustafa Kemal University Faculty of Medicine, Hatay-Turkey

Department of Emergency Medicine, Karadeniz Technical University, Farabi Hospital, Trabzon-Turkey

ABSTRACT BACKGROUND: The present objective was to evaluate clinical stages, complications, treatment modalities, and termination of treatment in patients who presented to the emergency department with snakebite. METHODS: A total of 132 snakebite cases were retrospectively examined using emergency department records. RESULTS: The majority of patients, 42.9% (n=57), had grade 0 snakebite. The local complication most frequently observed was pain (42.4%, n=56); the most common systemic complication was prolonged international normalized ratio (INR) level (5.3%, n=7). Local complications were observed in patients at all stages, while systemic complications were observed only in patients at advanced stages. Antivenom was administered in 46.4% (n=61) of patients, 52.2% (n=69) of patients were hospitalized, and 47.7% (n=63) of patients were discharged after 6–12 hours of monitoring. No negative outcome was observed during 6-month or year-long follow-up. CONCLUSION: Complications should be evaluated based on type of toxin, and appropriate treatment should be initiated efficiently, according to clinical stage. This approach reduces or prevents the development of complications. Keywords: Complications; snakebite; treatment.

INTRODUCTION Snakebite is a very serious health risk in tropical regions. It is estimated that Turkey hosts 40 species of snakes, though Viperidae are the most common. Snakebites may present with various clinical manifestations, including mild local symptoms, systemic complications, and death.[1,2] Level of toxicity depends upon several factors, including type and amount of venom injected, location of the bite, and sensitivity of the patient to poison. Graded clinical staging has been developed in order to facilitate treatment and monitorization.[2] Treatment is administered according to clinical stage, preventing Address for correspondence: Ali Karakuş, M.D. Mustafa Kemal Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, 31100 Hatay, Turkey Tel: +90 326 - 229 10 00 E-mail: drkarakus@yahoo.com Qucik Response Code

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or reducing complications. The present aim was to evaluate cases of snakebite in terms of clinical stage, complications, treatment modalities, and clinical termination of treatment in patients who presented to the emergency department.

MATERIALS AND METHODS Records of 132 patients who presented with snakebite were retrospectively analyzed. All patients were evaluated in terms of age, gender, site of bite, local and systemic complications, clinical stages (Table 1), treatment, and results.[2] All laboratory findings were collected from the laboratory information system and are shown in Table 2. All patients were evaluated, and antivenom therapy was administered according to clinical stage. European viper antiserum provided by Turkey’s Health Ministry was used (10-mL flacon, administered intramuscularly or intravenously, or 100 mg/mL horse immunoglobulin), in addition to 1 mg/kg steroid, 1 mg/kg pheniramine, and 1 mg/kg ranitidine, initiated for allergenic prophylaxis. Antivenom was administered by intravenous controlled infusion with 100 cc of serum physiologic in 60 min. Data were analyzed using SPSS software (version 21.0; SPSS Inc., Chicago, IL, USA). 333

Şahan et al. Evaluation of patients with snakebite who presented to the emergency department

Table 1. Clinical grading, antivenom usage, and monitoring steps Degree of poisoning

Clinical condition

Not used

Monitoring

No poisoning

Puncture wounds can be seen,

Not used

The patient can be discharged after 8 hours

Grade 0

No local or systemic signs

Mild Poisoning

Mild tissue swelling, eccihymosis,

Grade I

no systemic symptoms,

of monitoring. Not used

The patient can be discharged after 12 hours of monitoring.

Normal laboratory findings (normal thrombocytes count) Systolic blood pressure >90 mmHg Moderate Poisoning

Advanced swelling,

Two flacons of antivenom

The patient should be monitorized closely

Grade II

Pain, eccihymosis, prolonged PTT,

are recommended.

during therapy.

Thrombocytes count <80.000/µL, Systolic blood pressure >90 mmHg Severe Poisoning

Advenced swelling, pain, necrosis

Four flacons of antivenom

The patient should be monitored in the

Grade III

and bullouse lesions can be seen.

are recommended.

intensive care unit.

Prolonged PTT, Thrombocytes count <80.000/µL, Sistolic blood pressure <80 mmHg, Severe systemic symptoms and coagulopathies (bleeding from nose and stomach etc.)

RESULTS Thirty-one (23.1%) female and 101 (76.5%) male patients aged between 3 and 84 years were enrolled. The site of 71 (54.2%) bites was an upper extremity, the site of 60 (45.4%) was a lower extremity, the site of 1 was the neck. Clinically graded stages were as follows: 57 (42.9%) cases were grade 0; 38 (28.6%) cases were grade I; 29 (22%) cases were grade II; and 8 (6.5%) cases were grade III. Local complications were observed at all stages; systemic complications were observed only at advanced stages. The most common local complication was pain (n=56, 42.4%) (Table 3). In laboratory evaluation, routine parameters were analyzed. Serum glucose levels, alanine aminotransferase and aminotransferase activities, and sodium and potassium levels were normal. All echocardiograms showed normal activity. Mean Glasgow Coma Scale scores of patients were 14–15 (Table 4). Prothrombin time (PT) and partial thromboplastin time (PTT) were prolonged, compared to control levels measured 12 hours later. Increased white blood cell (WBC >10.2x103/µL) counts were detected in 44 patients at time of admission, while leukocytosis was detected in 18 patients during control evaluation. 334

However, no significant relationship between WBC counts and clinical stages was determined. Erythrocyte suspension was administered for patients with hemoglobin values below Table 2. Laboratory findings of patients Laboratory tests

Mean±SD

White blood cell (x103/µL) 11.6±6.2 Hemoglobin (g/dL) Hematocrit (%)

14±1.8 41.7±4.9

Platelet (x103/µL) 239.1±104.3 Glukoz (mg/dl) Blood urea nitrogen (mg/dL)

137.7±68.7 19.9±9

Crea (mg/dL)

0.7±0.2

Aspartate aminotransferase (U/L)

26.2±9.9

Alanine aminotransferase (U/L)

19.1±8.3

Na (mEq/L)

137.8±3.5

K (mEq/L)

4.1±0.5

Prothrombin time (s)

13.8±2.1

Partial thromboplastin time (s)

23.8±5

International normalized ratio

1.1±0.2

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Şahan et al. Evaluation of patients with snakebite who presented to the emergency department

Table 3. Patient grades and local complications

Table 5. Patient grades and treatment modalities

Complication n % Grade

Treatment

n % Grade

Pain

56 42.4 0–3

Antibiotherapy (1000 mg Amoxicillin

Erythema

51 38.6 1–3

+ 200 mg clavulanate)

Edema

45 34.0 1–3

Tetanus prophylaxis

125

94.74

0–3

Necrosis

10 7.5 1–3

Snake antivenom

46.42

2–3

Paresthesia

3 2.2 1–2

Immobilization

35 27.72 2–3

Cellulitis

Mannitol

21 16.41 3

2.2

1–2

132

100.0

5.30

0–3

Erythrocytes suspension

Fasiotomi-debridement-grafting

2 1.51 3

Table 4. Patient grades and systemic complications Complication

n % Grade 5.3

bites were considered to be grade 0. These patients were discharged following 6 hours of monitoring. No mortality was observed, and no complications were observed during the 1-year monitoring period.

PT, PTT and INR abnormalities

Anemia

6 4.5 3

Increased BUN and creatinine levels

3.7

Nausea and vomiting

2.2

DISCUSSION Snake venom can cause a variety of clinical conditions, according to the type and amount of toxin, the type of snake, and the susceptibility of the patient. Patients are treated and monitored according to clinical grading.[2] Snake venom has various toxic effects on the region of the bite and on the entire body, including local complications such as pain and swelling at the site, edema, erythema, necrosis, and cellulitis, as well as systemic complications such as fever, nausea and vomiting, compartment syndrome, heart failure, arrhythmias, acute renal failure, shock, coma, or death (Fig. 1a-c).[3,4]

Confusion

1.5

Compartment syndrome

1.5

Abnormal vital findings

1.5

Thrombocytopenia

1 0.7 3

Dispnoea

1 0.7 3

Anaphlaxis due to snake antivenom

0.7

Periorbital edema

0.7

PT: Prothrombin time; PTT: Partial thromboplastin time; INR: International normalized ratio; BUN: Blood urea nitrogen.

12.2 g/dL (6.5–7.2–6.6–7.7–7.0–6.8 g/dL) and hematocrit levels below 37.7% (19.2–21.9–19.9–25.1–21.2–21.9%). Patient stages and treatments are described in Table 5. Sixty-nine (52.2%) patients were hospitalized, 3 of whom had grade III bites and were transferred to the intensive care unit. Sixty-three patients were monitored in the emergency department, where no complications were observed and the

(a)

(b)

Patients are treated according to recommended protocols. Dry bites without envenomation are scored as grade 0, and bites that lack systemic signs or symptoms are scored as grade I. Antibiotherapy, tetanus vaccine, and symptomatic therapy are administered in these cases. Antivenom is the main treatment option in cases of venomous snakebite.[5,9] Rate of antivenom therapy ranges from 16–80%.[1,5,6] Antivenom therapy should be administered to

(c)

Figure 1. (a) Edema, necrosis and ecchymosis following snakebite. (b) Necrosis and diabetic foot following snakebite. (c) Shock and coma following snakebite on the face. Mechanical ventilation was administered to this patient.

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Şahan et al. Evaluation of patients with snakebite who presented to the emergency department

patients with advancing local or systemic complications. In a study conducted by Karakuş et al., the rate of complication was reported as 2.4%, while rates ranging between 20–75% have been reported elsewhere.[1,5,7–9]

We believe that this approach may prevent or decrease the number of complications.

In the present emergency department, antivenom therapy was administered to 61 (46.4%) patients, all of whom had grade II or III bites. Anaphylactic reaction due to antivenom administration was observed in only 2 patients. However, they were discharged following improvement, which may have been the result of administration of steroid and antihistaminic therapy for prophylaxis prior to antivenom administration.

REFERENCES

Snake venom includes a variety of toxins and consists of 70% water and 30% protein substances, including leukotrienes, phospholipases, acetylcholinesterase, hyaluronidase, collagenase, antibactericides, neurotoxins, hemotoxins, anticoagulants, cardiotoxins, hemolytic factors, fibrinolytic enzymes, quinine, and histamine.[10,11] Toxins can cause diverse systemic effects, such as leukocytosis, thrombocytopenia, hypofibrinogenemia, bleeding disorders, proteinuria, and azotemia.[4,12,13] However, leukocytosis has been primarily reported as a laboratory finding.[5,14] The most common venomous snakes in Turkey have neurotoxins and hemotoxins, and belong to the Viperidae family.[4] In the present study, bleeding disorder and anemia were the most common systemic complications. Antivenom and erythrocyte suspension were administered. Daily hemogram, and PT, PTT, and international normalized ratio (INR) monitoring can aid in the prevention of complications. Patients should be evaluated according to grade of bite and clinically treated. Patients with grade 0 or I bites, with no systemic complications, can be discharged after 12 hours of monitoring.[2,15–17] Symptomatic treatment should be administered. Death can result from insufficient therapy. According to the World Health Organization, about 35000–50000 people die annually from snakebites.[2] In the present study, 69 (52.2%) patients were hospitalized, and 63 (47.7%) were discharged following improvement after 6–12 hours of monitoring. No deaths or negative outcome were observed during 1-year follow-up, the result of accurate clinical grading, monitoring, and treatment.

Conclusions Complications resulting from toxins of snake venom should be evaluated, and appropriate treatment should be efficiently administered according to snakebite grade. Patients should be monitored with daily hemogram and bleeding diathesis tests.

336

Conflict of interest: None declared.

1. Karakus A, Zeren C, Celik MM, Arica S, Ozden R, Duru M, et al. A 5-year retrospective evaluation of snakebite cases in Hatay, Turkey. Toxicol Ind Health 2015;31:188–92. 2. Kara ME, Ay MO, Seğmen S, Avcı A, İçme F, Gökel Y. Management of Snake Bites. Archives Medical Review Journal 2014;23:272–92. 3. Karakus A, Ozkan M, Karcioglu M, Ozden R, Ustun I, Caliskan K, et al. Diabetic foot due to anaphylactic shock: a case report. Arch Trauma Res 2014;3:17610. 4. Sönmez BM, Yılmaz F, Yılmaz MS, Kavalcı C, Gökhan Ş, Akbulut AS, et al. Clinical Aspects and Emergent Management of Snake Bites Presented to Emergency Department. J Clin Anal Med 2015;6:558–61. 5. Bulut M, Eren Ş, Özdemir F, Köksal O, DurmuŞ O, Esen M, et al. Snakebite cases admitted to Uludağ University Faculty of Medicine Emergency Department and current management of snake bite. Akademik Acil Tıp Dergisi 2009;8:31–4. 6. Moreno E, Queiroz-Andrade M, Lira-da-Silva RM, Tavares-Neto J. Clinical and epidemiological characteristics of snakebites in Rio Branco, Acre. [Article in Portuguese] Rev Soc Bras Med Trop 2005;38:15–21. 7. Açikalin A, Gökel Y, Kuvandik G, Duru M, Köseoğlu Z, Satar S. The efficacy of low-dose antivenom therapy on morbidity and mortality in snakebite cases. Am J Emerg Med 2008;26:402–7. 8. Jenkins JL, Break GR. Manual of emergency medicine. Philadelphia, PA: Lippincott Williams & Wilkins; 2000. 9. Satar S, Karcıoglu O, Sebe A. An usual localization of snakebite antivenin Treated without: a case report. The Mount Sinai Journal of Medicine 2005;72:116–9. 10. Koh DC, Armugam A, Jeyaseelan K. Snake venom components and their applications in biomedicine. Cell Mol Life Sci 2006;63:3030–41. 11. Ouyang C, Teng CM, Huang TF. Characterization of snake venom components acting on blood coagulation and platelet function. Toxicon 1992;30:945–66. 12. Gökel Y, Başlamışlı F, Koçak R. Çukurova yöresinde yılan ısırmaları. Çukurova Üniversitesi Tıp Fakültesi Dergisi 1997;22:184–8. 13. Gundappa RK, Sud K, Kohli HS, Jha V, Gupta KL, Joshi K, et al. Snakebite induced acute interstitial nephritis: report of a rare entity. Ren Fail 2002;24:369–72. 14. Santoro ML, Sano-Martins IS, Fan HW, Cardoso JL, Theakston RD, Warrell DA. Haematological evaluation of patients bitten by the jararaca, Bothrops jararaca, in Brazil. Toxicon 2008;51:1440–8. 15. Johnston MA, Tullett WM. Adder (Vipera berus) bites: a case report and review of the management for emergency medical personnel. Arch Emerg Med 1993;10:375–9. 16. Chang KP, Lai CS, Lin SD. Management of poisonous snake bites in southern Taiwan. Kaohsiung J Med Sci 2007;23:511–8. 17. Köse R. The management of snake envenomation: evaluation of twentyone snake bite cases. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2007;13:307–12.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Acil servise başvuran yılan ısırması olgularının değerlendirilmesi: 132 olgu Dr. Mustafa Şahan,1 Dr. Veyis Taşın,1 Dr. Ali Karakuş,1 Dr. Oğuzhan Özcan,2 Dr. Umut Eryiğit,3 Dr. Güven Kuvandık1 1 2 3

Mustafa Kemal Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Hatay Mustafa Kemal Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Hatay Karadeniz Teknik Üniversitesi, Farabi Hastanesi, Acil Tıp Anabilim Dalı, Trabzon

AMAÇ: Bu çalışmada, yılan ısırması nedeni ile acil servise getirilen hastaların klinik evreleri, gelişen komplikasyonlar, yapılan tedaviler ve sonuçları değerlendirildi. GEREÇ VE YÖNTEM: Bu amaçla acil servise yılan ısırması nedeni ile getirilen 132 olgu hastane kayıtlarından geriye dönük olarak incelendi. BULGULAR: Hastaların %42.9’u (n=57) Evre 0 düzeyindeydi. En sık görülen lokal komplikasyon ağrı (n=56; %42.4) iken sistemik komplikasyon International Normalized Ratio (INR) değerinde uzama %5.3 (n=7) idi. Lokal komplikasyonlar her evrede görülebilirken sistemik komplikasyonlar ileri evrelerde görüldü. Yılan antivenomu %46.4 (n=61) hastaya uygulandı. Altmış dokuz hasta (%52.2) hastaneye yatırılırken, 63 hasta (%47.7) acil servisteki 6–12 saatlik gözlem sonrası şifa ile taburcu edildi. Ölüm olgusu görülmedi. Olgulardan altı aylık ve bir yıllık sürede olumsuz geri bildirim alınmadı. TARTIŞMA: Yılan ısırması olgularında yılan zehirinde bulunan toksinlere göre oluşabilecek komplikasyonlar değerlendirilmeli ve uygun tedavi evrelere göre zamanında başlanmalıdır. Bu yaklaşım komplikasyonların gelişimini engeller veya azaltır. Anahtar sözcükler: Komplikasyon; tedavi; yılan ısırması. Ulus Travma Acil Cerrahi Derg 2016;22(4):333–337

doi: 10.5505/tjtes.2016.03392

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ORIGIN A L A R T IC L E

Role of endothelial nitric oxide synthases system on acute appendicitis Bahadır Taşlıdere, M.D.,1 Elif Funda Şener, M.D.,2* Elif Taşlıdere, M.D.,3 Nahide Ekici Günay, M.D.,4 Oğuzhan Bol, M.D.,5 Emre Bülbül, M.D.,5 Ramazan Sami Aktaş, M.D.,6 Nurullah Günay, M.D.6 1

Department of Emergency Medicine, Bingöl State Hospital, Bingöl-Turkey

Department of Medical Biology, Erciyes University Faculty of Medicine; *Erciyes University Genom and Stem Cell Center, Kayseri-Turkey

Department of Histology and Embryology, Bezmialem Vakif University Faculty of Medicine, İstanbul-Turkey

Department of Clinical Biochemistry, Kayseri Training and Research Hospital, Kayseri-Turkey

Department of Emergency Medicine, Kayseri Training and Research Hospital, Kayseri-Turkey

Department of Emergency Medicine, Erciyes University Faculty of Medicine, Kayseri-Turkey

ABSTRACT BACKGROUND: Obstruction and inflammation of the appendix lumen is the leading physiopathological process during acute appendicitis (AA). Although the relationship between inflammation and endothelial nitric oxide synthases (eNOS) has been well described, no recent data describing the relationship between inflammation during AA and polymorphism of the eNOS gene has been reported. Given the limited data available, we believed that defining the relationship between AA and eNOS would be a beneficial contribution. METHODS: A total of 201 patients admitted to the emergency department with AA and 201 healthy volunteers selected from among the relatives of patients were included. Polymorphism of the eNOS was assessed. RESULTS: Intron 4a/4a was positive in 119 participants, genotype G894T GT was positive in 71 patients with AA, and 786-1 was positive in 71 patients with AA. These results suggest that no statistically significant correlation exists between genotypes of AA patients and control subjects regarding 4a/b, G894-GT, and 786-1 eNOS polymorphisms. CONCLUSION: Though the present results suggest that no statistically significant correlation exists between AA and eNOS gene polymorphism, to claim otherwise is also impractical. We believe that the present results will lay the groundwork for future, larger studies. Keywords: Acute appendicitis; genetic polymorphism; nitric-oxide-synthases.

INTRODUCTION Acute appendicitis (AA), a leading cause of emergency department admittance, has been the subject of many studies. The primary pathophysiological process behind AA has been accepted as the obstruction of the appendix lumen and consequent inflammation.[1–3] However the relationship between Address for correspondence: Nurullah Günay, M.D. Erciyes Üniversitesi Hastaneleri Acil Servis Anabilim Dalı, Köşk Mah., Prof. Dr. Turhan Feyzioğlu Cad., No: 42, 38039 Kayseri, Turkey Tel: +90 536 - 254 52 09 E-mail: ngemergency@yahoo.com Qucik Response Code

338

inflammation and obstruction has yet to be clearly defined— which is the cause and which the effect remains vague. Likewise, obstruction of the appendix lumen by an ingested fruit pit may cause AA, though not all who ingest a pit will develop AA. Therefore, there is need for further study of the inflammatory process and development of AA. Nitric oxide (NO), a well-studied signal molecule, is located within the smooth muscle cells and plays a role not only in several gastrointestinal functions, but also in defense system and immunologic reactions. During inflammatory processes, NO was found to be an important factor in vasodilatation, changes in vascular permeability, extravasation, and leukocyte migration and activation.[4,5] Genetic polymorphism of endothelial nitric oxide synthases (eNOS), an isoform of nitric oxide synthases (NOS), which is an enzyme in NO synthesis, is correlated to basal NO levels.[6] It has been suggested that NO levels rise in cases of AA.[7–9] Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Taşlıdere et al. Role of endothelial nitric oxide synthases system on acute appendicitis

While eNOS has been described as closely related to inflammation,[10] few studies have focused on the relationship between inflammation in AA and genetic polymorphism of eNOS. The focus of the present study was eNOS gene polymorphism in patients with AA.

MATERIALS AND METHODS The present study was conducted via collaboration of the departments of emergency medicine and medical biology at Erciyes University, a tertiary hospital with a catchment area of 15 million, and an emergency department admittance of 110000. It was approved by the local ethics committee (on August 15th, 2014; no: 490). Blood samples were obtained from AA patients who presented to the emergency department and were genetically analyzed in the Genome and Stem Cell Center (GENKOK), located in the same university. Procedures were performed by an experienced emergency department physician who was not involved in patient treatment.

Patient Selection and Sampling Included were those who presented to the emergency department with symptoms of stomachache accompanied by nausea, vomiting, and loss of appetite (known as “first 6-hour signs”)[11] and who were diagnosed with AA following routine workup. Patients who died shortly after surgery and who were not pathologically diagnosed with AA were excluded. Routine blood workup included complete blood count (CBC), neutrophil-leukocyte ratio, glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium, potassium, chloride, lactate dehydrogenase (LDH) levels, and direct and indirect bilirubin. There was no age limit as inclusion criteria. Routine radiological workup consisted of ultrasonography, computed tomography, or both. This study did not affect the diagnosis or treatment of AA. Complaints, signs and symptoms, and CBC were computed according to the Alvarado scoring system.[12] This system, with a maximum score of 10, has 8 parameters, 3 of which are related to symptoms, 4 of which are related to clinical signs, and 3 of which are related to CBC.[13] Higher scores more strongly indicate AA, with a sensitivity of 80%.[14] A score of below 5 indicates decreased likelihood of AA, a score of 5 or 6 indicates a weak likelihood of AA, a score of 7 or 8 indicates possible AA, and a score of 9 or 10 indicates a strong probability of AA. The control group consisted of volunteers, selected among the relatives of AA patients. Similar blood sampling was performed in the control group. Following oral and written consent, 2 mL of blood was drawn into tubes containing ethylenediaminetetraacetic acid as anticoagulant. Samples were kept at +4°C until genetic analysis.

Genetic Analysis All genetic studies were conducted in the GENKOK labora-

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tory of Erciyes University. eNOS gene polymorphisms were analyzed following genomic DNA extraction from peripheral blood leukocyte samples of all participants, using a High Pure Polymerase Chain Reaction (PCR) Template Preparation Kit (Roche Diagnostics International AG, Rotkreuz, Switzerland). For the detection of the eNOS-786TC polymorphism, PCR-restriction-fragment-length polymorphism analysis was used. PCR reaction was carried out using 10 pmol of each primer: 5’-AGGCCCTATGGTAGTGCCTT-3’ (forward) and 5’-TCTCTTAGTGCTGTGGTCAC-3’ (reverse). For each PCR, 10 ng DNA was amplified in a final volume of 50 µL at an annealing temperature of 60°C. After PCR detection, Mspl (Thermo Fisher Scientific, Inc., Waltham, MA, USA) restriction endonuclease digestion was performed for 16 h at 37°C. Final PCR products were analyzed by electrophoresis on 3% agarose gel. The eNOS 4a/4b polymorphism was detected only by PCR amplification. PCR reaction was carried out using the primers 5’-AGGCCCTATGGTAGTGCCTT-3’ (forward) and 5’-TCTCTTAGTGCTGTGGTCAC-3’ (reverse). This procedure was based on DNA amplification in a final volume of 50 µL, followed by heating at 56°C. PCR products were analyzed by electrophoresis on 2% agarose gel.[15] Ten μg of genomic DNA of each participant was amplified by PCR for eNOS G894T polymorphism. The 50-μL reaction mixture contained forward 5’-CATGAGGCTCAGCCCCAGAAC-3’ and reverse 5’-AGTCAATCCCTTTGGTGCTCAC-3’ primers, amplifying at 60°C. PCR products were then subjected to overnight incubation at 37°C with 1U of Mbol restriction endonuclease (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Digestion products were separated using 2.5% agarose gel electrophoresis and stained in ethidium bromide (Table 1).[16]

Statistical Analysis Data were evaluated with SPSS software (version 22.0; SPSS Inc., Chicago, IL, USA). Descriptive statistics and inferential statistics were used for evaluation. Shapiro-Wilk test was conducted to assess normality, and Bonferroni test was used in multivariate analysis. Strength of relation between variables was measured with Pearson correlation analysis. Discrepancy of age between patient and control groups was compared with Student’s t-test, and categorical variables were compared with chi-square test. A value of p<0.05 was accepted as statistically significant. Table 1. Polymerase chain reaction program and restriction enzymes for genotyping eNOS gene polymorphisms eNOS gene polymorphism Intron 4 (4a/4b) (rs61722009)

Restriction Annealing enzyme temperature (°C) –

894G>T (rs1799983)

Mbol

-786 T>C (rs2070744)

Mspl

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Taşlıdere et al. Role of endothelial nitric oxide synthases system on acute appendicitis

Table 2. Gender parameters Variables

Study group

Control group

n (%)

Male

113 (51)

109 (49)

222

Female

88 (49)

92 (51)

180

201

402

χ2= 0.161

p=0.688

Total

Table 3. Main complaint at admittance Complaint at admittance

Stomachache

147 73

Nausea

14 7

Vomiting

14 7

Loss of appetite

Stomachache, nausea, vomiting

Total

201 100

CBC provided the following data: white blood cell count had a mean of 14.1±3.8 mg/dL (min-max: 7.8–36.2 mg/ dL); thrombocyte count had a mean of 240.0±89.3/mm3 (min-max: 104–594/mm3); hemoglobin count had a mean of 13.6±1.9 mg/dL (min-max: 8.2–17.1 mg/dL); and neutrophil-lymphocyte ratio had a mean of 3.7±1.1 (min-max: 1.9–6.9). Blood glucose levels were 56–147 mg/dL (mean: 97.6±11.9 mg/dL), BUN was 4–50 mg/dL (mean: 13.5±6.3 mg/dL), creatinine was 0.09–1.55 mg/dL (mean: 0.6±0.2 mg/ dL), AST was 6–55 U/L (mean: 21.3±9.9 U/L), ALT was 3–89 U/L (mean: 16.5±11.6 U/L), sodium was 131–144 mmol/L (mean: 139.2±1.9 mmol/L), potassium was 3–5.7 mmol/L (mean: 4.2±0.4 mmol/L), total bilirubin was 0.1–5.3 mg/dL (mean: 0.7±0.5 mg/dL), and LDH 142 was 652 IU/L (mean: 254.0±103.9 IU/L) (Table 5). A total of 116 patients were evaluated with ultrasonography, 48 patients with computed tomography, and 37 patients with both methods (Table 6). Using the Alvarado system, 12 patients (6%) had a score of 5 or 6, 128 patients (64%) had a score of 7 or 8, and 61 patients (30%) had a score of 9 or 10.

Genetic Analysis Data Clinical and laboratory findings for study and control groups The patient group consisted of 88 females and 113 males between ages of 3 and 80 years (mean: 29.6±15.8). The control group consisted of 92 females and 109 males with a mean age of 29.7±16.0 years. There was no age discrepancy between groups (p>0.05). In addition, correlation of age and gender parameters with eNOS intron 4 genotypes was not statistically significant (p>0.05) (Table 2). Primary complaints in the patient group were: stomachache in 147 patients (73%), nausea in 14 (7%), vomiting in 14 (7%), loss of appetite in 8 (4%), and all 3 signs in 18 patients (9%) (Table 3).

Endothelial NOS genotype and allele distribution for each group were determined. From among the 3 genotypes for intron 4, 12 participants had genotype 4a/4a, 119 participants had genotype 4b/4a, and 271 participants had genotype 4b/4b. Of the participants with genotype 4a/4a, 7 (58%) were from the patient group, and 5 (42%) were from the control group. Of the participants with genotype 4b/4a, 60 (50%) were from the patient group, and 59 (50%) were from the control group. Of the participants with genotype 4b/4b, 134 (49%) were from the patient group, and 137 (51%) were from the control group. Distribution of genotypes between patient and control groups were statistically insignificant (p=0.852) (Table 7).

Regarding vital signs, body temperature was between 36oC and 38.3°C (mean 36.7±0.58°C). Systolic and diastolic blood pressures were 90–180 mmHg (mean: 121.1±13.5 mmHg) and 41–113 mmHg (mean: 73.2±11.4 mmHg), respectively. Respiration rate was 18–28 bpm (mean: 20.1±1.4 bpm). Cardiac pulse rate was measured as 68–103 beats per minute (mean: 87.4±21.5 beats per minute) (Table 4).

The GG genotype of eNOS-894 polymorphism was found in 112 patients (56%) and 119 healthy volunteers (60%), the TT genotype was found in 18 patients (9%) and 16 healthy volunteers (8%), and the GT genotype was found in 71 patients (36%) and 66 healthy volunteers (33%). Correlation between patient and control groups regarding eNOS-894 polymorphism was not statistically significant (p=0.774) (Table 7).

RESULTS

Table 4. Vital signs Variables Body Temperature (°C) Systolic/diastolic (mmHg)

Mean±SD

Minimum-Maximum

36.7±0.58

36–38.3

121.1±13.5/73.2±11.4

90-180/41–113

Respiratory rate/min

20.1±1.4

18–28

Cardiac pulse rate/min

87.4±21.5

68–103

SD: Standard deviation.

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Table 5. Complete blood count and blood biochemistry parameters

Table 7. Gender and genotype distributions of the groups

Variables Mean±SD Minimum Maximum

Variables

White blood cell (mg/dL)

Gender 0.688

Thrombocyte (/mm3)

14.1±3.8

7.8–36.2

240.0±89.3 104–594

Patients Controls (n=201) (n=201) (%) (%)

Male

113 (51)

109 (49)

Female

88 (49)

92 (51)

Hemoglobin (mg/dL)

13.6±1.9

8.2–17.1

Neutrophil-lymphocyte ratio

3.7±1.1

1.9–6.9

eNOS Intron 4

Glucose (mg/dL)

97.6±11.9

56–147

4b/4b

134 (49)

137 (51)

BUN (mg/dL)

13.5±6.3

4–50

4b/4a

60 (50)

59 (50)

Creatinine (mg/dL)

0.6±0.2

0.09–1.55

4a/4a

7 (58)

5 (42)

AST (u/L)

21.3±9.9

6–55

ALT (u/L)

16.5±11.6

3–89

112 (56)

119 (60)

Sodium (mmol/l)

139.2±1.9

131–144

71 (36)

66 (33)

Potassium (mmol/l)

4.2±0.4

3.0–5.7

18 (9)

16 (8)

Total bilirubin (mg/dL)

0.7±0.5

0.1–5.3

eNOS -786T>C

254.0±103.9

142–652

LDH (IU/L)

0.852

eNOS G894T

71 (36)

80 (40)

6 (3)

8 (4)

124 (62)

113 (57)

0.774

0.514

Table 6. Radiological evaluation method

Number of patients

Ultrasonography only

116

Computed tomography only

Both methods

Total

201 100

The 786-1 genotype of eNOS-786 polymorphism was positive in 71 patients (36%) and 80 healthy volunteers (40%), the 786-2 genotype was positive in 6 patients (3%) and 8 healthy volunteers (4%), and the 786-3 genotype was positive in 124 patients (62%) and 113 healthy volunteers (57%). These results showed no statistically significant relationship between the patient and volunteer groups (p=0.514) (Table 7).

DISCUSSION The present focus was on the probable involvement of eNOS in the pathophysiology of AA. Though the role of eNOS in inflammation processes has been well defined, no statistically significant findings were presently reached, a conclusion that is discussed below. Still, the present results also point to the difficulty in denying the existence of this relationship. Definitive conclusions require further study, utilizing larger patient and control groups. We believe that our findings have potential importance, but that the limited number of included cases prohibits the formation of precise conclusions. We consider the present to be an entry study in the description of a possible relationship between eNOS and AA inflammation. Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

The most important physiopathological process in the etiology of AA is thought to be the obstruction of the appendix lumen due to fecaloma or other factors that cause inflammation.[17–19] On the other hand, as not all cases with such factors advance AA, and other components may have a physiopathological role in AA. NO, which has been studied in this context since the 1980s, is a free radical molecule that is chemically unstable in nature, but essential in local vascular stability. Its half-life is very short, 5–10 seconds, and it has several anti-inflammatory, anti-oxidant, and anti-fibrotic functions in the relaxation of smooth muscle and aggregation of leukocytes and thrombocytes.[20–22] The present study was based on the hypothesis that AA inflammation may be caused by a defect in the NO mechanism, which functions normally in anti-inflammatory processes, challenging the finding stated elsewhere that NO levels rise in cases of AA. Our opposition was due to the short half-time of NO, its unstable nature, and other factors yet unknown. It is known that NO, an inhibitor in the coordination of tonic and motility functions throughout the gastrointestinal tract, from the esophagus to the anal sphincter, also has secretory influence in physiopathological conditions.[23] Given the complicated nature of these processes and physiopathological circumstances, the relationship between NO and AA seems yet to be clearly understood. Our results suggest that the working mechanism of NOS, which is involved in the synthesis of NO, is unable to account for the entire mechanism in cases of AA. We believe that this is related to the 3 different isoen341

Taşlıdere et al. Role of endothelial nitric oxide synthases system on acute appendicitis

zymes of NOS, which will hopefully be the subject of future studies.[24] The eNOS gene is located on the terminal part of 7q32-q, and its polymorphic structure has been described in several pathologies, including coronary heart disease and hypertension.[25,26] Similarly, it is thought that AA may have a genetic background. In more detail, a polymorphism in the gene that codes the eNOS enzyme may affect gene expression, which may cause eNOS activity, and therefore inflammatory response, leading to AA. Patients presently evaluated were carefully chosen from among those admitted to the emergency department with AA. Clinical and laboratory features of patients were presented in the results section, but are not discussed here, as they are irrelevant to the present genetic focus. The patient and control groups were evaluated regarding allele and genotype distribution. Intron 4 positivity was investigated in 3 genotypes, and the most common genotype with intron 4 positivity was identified as homozygote 4b/4b. However, this result was not statistically significant, compared to frequency in other groups. Regarding the heterozygote 4b/4a genotype, there was statistically significant difference between groups. However, positivity was identified in around 60 individuals, from among the control and patient groups. No significant polymorphism regarding the intron 4 genotype in AA patients was identified in this initial study. Future studies will include other types of polymorphism. In AA patients, the eNOS-894 GG genotype was detected in 112 patients, the eNOS-894 GT in 71, and the eNOS-894 TT in 18. However, these results had no statistical significance. The eNOS-786-TT, eNOS-786-TC and eNOS-786-CC genotypes were found in 71, 6, and 124 patients, respectively. As the present findings had no statistical significance, we believe that there is no relationship between AA and eNOS gene polymorphism.

Conclusion We conclude that eNOS gene polymorphism is not related to AA.

Acknowledgement

3. Ilves I, Fagerström A, Herzig KH, Juvonen P, Miettinen P, Paajanen H. Seasonal variations of acute appendicitis and nonspecific abdominal pain in Finland. World J Gastroenterol 2014;20:4037–42. 4. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derivedrelaxing. Nature 1987;327:524–6. 5. Coleman JW. Nitric oxide in immunity and inflammation. Int Immunopharmacol 2001;1:1397–406. 6. Sipahi T, Güldiken B, KabayelL,Palabıyık O, Özkan H, Okman Kılıç T, et al. Endothelial Nitric Oxide Synthase and Angiotensin Converting Enzyme Gene Polymorphisms in Migraine Patients. Archives of Neuropsychiatry/NoropsikiatriArsivi 2013;50:274–8. 7. Yilmaz FM, Yilmaz G, Erol MF, Köklü S, Yücel D. Nitric oxide, lipid peroxidation and total thiol levels in acute appendicitis. J Clin Lab Anal 2010;24:63–6. 8. Aktimur R, Gokakin AK, Deveci K, Atabey M, Topcu O. Oxidative stress markers in laparoscopic vs. open appendectomy for acute appendicitis: A double-blind randomized study. J Minim Access Surg 2016;12:143–7. 9. Kavakli HS, Erel O, Becel S. Oxidativestress in diagnosis of acute appendicitis patients. Scientific Research and Essays 2011;6:1766–70. 10. Lee J, Cho JY, Kim WK. Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats with diet-induced atherosclerosis. Nutr Res Pract 2014;8:284–91. 11. McDonnell R, Delany V, Dack P, Johnson H. Changing trend in congenital abdominal wall defects in eastern region of Ireland. Ir Med J 2002;95:236–8. 12. Rodrigues G, Rao A, Khan SA. Evaluation of Alvarado score in acute appendicitis: a prospective study. Internet J Surg 2006;9:1–5. 13. Kalan M, Talbot D, Cunliffe WJ, Rich AJ. Evaluation of the modified Alvarado score in the diagnosis of acute appendicitis: a prospective study. Ann R Coll Surg Engl 1994;76:418–9. 14. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. 15. Şener EF, Emiroğulları ÖN, Serhatlıoğlu F, Özkul Y. The role of endothelial nitric oxide synthase gene G894T and intron 4 VNTR polymorphisms in hemodialysis patients with vascular access thrombosis. Anadolu Kardiyol Derg 2014;14:239–43. 16. Kocyigit I, Taheri S, Sener EF, Unal A, Eroglu E, Öztürk F, et al. Endothelial nitric oxide synthase gene expression is associated with hypertension in autosomal dominant polycystic kidney disease. Cardiorenal Med 2014;4:269–79. 17. Kozar RA, Roslyn JJ. Theappendix. In: Schwartz SI, editor. Principles of surgery. Vol. 2, 7th ed. New York: McGraw-Hill; 1999. p. 1383–94. 18. Condon RE, Telford GL. Appendicits. In: Sabiston DC. Textbook of Surgery. 14th ed. Philadelphia: W.B. Saunders; 1991. p. 884–98.

This study was supported by a project (TTU-2014-5595) from the Scientific Research Projects Department of Erciyes University, Kayseri, Turkey.

19. Green SM, Schmidt SP, Rothrock SG. Delayed appendicitis from an ingested foreign body. Am J Emerg Med 1994;12:53–6.

Conflict of interest: None declared.

21. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109–42.

REFERENCES

22. Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988;333:664–6.

1. Köksal H, Uysal B, Sarıbabıçcı R. Bir devlet hastanesinin akut apandisit tecrübesi. JAEM 2010;9:41–4.

23. Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 1994;78:915–8.

2. Shelton T, McKinlay R, Schwartz RW. Acute appendicitis: current diagnosis and treatment. Curr Surg 2003;60:502–5.

24. Rios DL, D’Onofrio LO, Souza JK, Queiroz AM, Raduy-Maron L, Silva-Neto N, et al. Smoking-dependent and haplotype-specific effects of

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Taşlıdere et al. Role of endothelial nitric oxide synthases system on acute appendicitis endothelial nitric oxide synthase gene polymorphisms on angiographically assessed coronary artery disease in Caucasian- and African-Brazilians. Atherosclerosis 2007;193:135–41. 25. Knowles JW, Reddick RL, Jennette JC, Shesely EG, Smithies O, Maeda N. Enhanced atherosclerosis and kidney dysfunction in eNOS(-/-)

Apoe(-/-) mice are ameliorated by enalapril treatment. J Clin Invest 2000;105:451–8. 26. Bonnardeaux A, Nadaud S, Charru A, Jeunemaitre X, Corvol P, Soubrier F. Lack of evidence for linkage of the endothelial cell nitric oxide synthase gene to essential hypertension. Circulation 1995;91:96–102.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisitte endotelial nitrik oksit sentaz sisteminin rolü Dr. Bahadır Taşlıdere,1 Dr. Elif Funda Şener,2 Dr. Elif Taşlıdere,3 Dr. Nahide Ekici Günay,4 Dr. Oğuzhan Bol,5 Dr. Emre Bülbül,5 Dr. Ramazan Sami Aktaş,6 Dr. Nurullah Günay6 Bingöl Devlet Hastanesi, Acil Tıp Kliniği, Bingöl Erciyes Üniversitesi Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, Genom ve Kök Hücre Merkezi, Kayseri 3 Bezmialem Vakıf Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, İstanbul 4 Kayseri Eğitim ve Araştırma Hastanesi, Tıbbi Biyokimya Kliniği, Kayseri 5 Kayseri Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Kayseri 6 Erciyes Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Kayseri 1 2

AMAÇ: Akut apandisit etiyolojisinde en önemli fizyopatolojik sürecin apandiks lümeninin bir nedenle obstrüksiyonu ve enflamasyonu olduğu bilinmesine rağmen, bu enflamasyon ile endotelial nitrikoksit sentaz (eNOS) gen polimorfizmi arasında yapılan bir araştırma bulunmamaktadır. Oysaki enflamasyon ile endotelial nitrikoksit sentaz ilişkisi birçok çalışmada gösterilmiştir. Literatürdeki eksik yerini hala koruyan akut apandisit ve endotelial nitrikoksit sentaz gen polimorfizmi muhtemel ilişkisi hipotezi araştırılmağa değer bulunmuştur. GEREÇ VE YÖNTEM: Araştırma için 201 akut apandisitli ve 201 kontrol grubu olmak üzere 402 birey incelemeye alındı. Acil servise başvuran akut apandisitli hastalardan çalışma grubu oluşturulurken, yakınlarından da kontrol grubu belirlendi. Çalışmada eNOS gen polimorfizmine ait genotipleri analiz edildi. BULGULAR: İntron 4b/4a’nin 119 bireyde pozitif olduğu görüldü. Genotiplerden G894T-GT’nin 71 ve nitrikoksit sentaz 786-1’in 71 akut apandisitli olguda pozitif olduğu saptanarak, bu sonuçlar ile AA hastaları ve kontrol grubu eNOS 4a/b, G894-GT ve 786-1 genotipleri arasında anlamlı bir fark bulunmadı. TARTIŞMA: Akut apandisit ve eNOS gen polimorfizmi muhtemel ilişkisi olarak hipotezi kurulan bu çalışmadan elde edilen sonuçlarda eNOS ile akut apandisit arasında istatistikî bir ilişki kurulmamıştır. Ancak, böyle bir ilişkinin olmadığını bu çalışma ile iddia etmek mümkün gözükmemektedir. Metodolojik açıdan elde edilen veriler önem taşımakta ve yapılacak daha geniş çalışmalar ile bu konu hakkında daha detaylı bilgiler elde edilebilecektir. Anahtar sözcükler: Akut apandisit; genetik polimorfizm; nitrik-oksit-sentaz. Ulus Travma Acil Cerrahi Derg 2016;22(4):338–343

doi: 10.5505/tjtes.2016.38202

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ORIGIN A L A R T IC L E

Diagnostic utility of the neutrophil-lymphocyte ratio in patients with acute mesenteric ischemia: A retrospective cohort study Yusuf Tanrıkulu, M.D.,1 Ceren Şen Tanrıkulu, M.D.,2 Mehmet Zafer Sabuncuoğlu, M.D.,3 Ayetullah Temiz, M.D.,4 Furuzan Köktürk, M.D.,5 Boran Yalçın, M.D.1 1

Department of General Surgery, Zonguldak Atatürk State Hospital, Zonguldak-Turkey

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

Department of General Surgery, Süleyman Demirel University Faculty of Medicine, Isparta-Turkey

Department of General Surgery, Erzurum Area Training and Research Hospital, Erzurum-Turkey

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

ABSTRACT BACKGROUND: Acute mesenteric ischemia (AMI) remains fatal in 50–70% of cases. AMI is recognized as a vascular emergency, requiring rapid and efficient clinical evaluation and treatment. In the present retrospective study, the possible utility of the neutrophillymphocyte ratio (NLR) in the early diagnosis of AMI was explored. The potential use of this ratio to distinguish AMI from non-vascular bowel necrosis (NVBN) was investigated. METHODS: A total of 58 AMI, 62 NVBN, and 62 control patients were enrolled between May 1, 2010 and April 30, 2015. Patients who underwent laparotomies and/or bowel resections to treat AMI were included, as were NVBN patients who underwent segmental bowel resection to treat incarcerated and strangulated hernias. Controls were patients who presented to the emergency room with non-specific abdominal pain. RESULTS: Mortality rate was 51.7% in the AMI and 4.8% in the NVBN groups. White blood cell (WBC) count, C-reactive protein (CRP) level, and red cell distribution width (RDW) were highest in the AMI group. NLR was higher in the AMI and NVBN groups than in the control group (p<0.001), though no difference in NLR was found between the AMI and NVBN groups. In addition, WBC count, CRP level, and NLR were higher in the NVBN group than in the controls (p<0.001). CONCLUSION: We suggest that preoperative NLR aids in the diagnosis of AMI, and can be used to distinguish this condition from NVBN. NLR should be calculated, in addition to clinical examination. Keywords: Acute mesenteric ischemia; diagnosis; NLR; serum markers.

INTRODUCTION Acute mesenteric ischemia (AMI), an abdominal emergency, is observed in 1 of every 1000 patients presenting to emergency rooms. Mortality from AMI remains high (40–70%), Address for correspondence: Yusuf Tanrıkulu, M.D. Mevlana Üniversitesi Tıp Fakültesi Hastanesi, Genel Cerrahi Anabilim Dalı, 42100 Konya, Turkey Tel: +90 372 - 252 19 00 E-mail: drtanrikulu@hotmail.com Qucik Response Code

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although diagnostic methods have advanced in recent years. An important contributor to mortality is the failure of timely diagnosis, as duration of ischemia affects AMI outcome.[1,2] A 24-hour delay reduces survival rate by 20%; early diagnosis is critical.[3] However, early AMI signs and symptoms on physical examination are vague, laboratory data are non-specific, and imaging methods including duplex ultrasonography and computerized tomographic angiography are not sufficiently sensitive when used to explore distal vascular pathologies.[4,5] Therefore, the development of new diagnostic methods is essential. An ideal biochemical marker should be highly specific and sensitive, measurable in a non-invasive manner, released from the intestinal mucosa, and should preferably be detectable in peripheral blood. AMI is an acute inflammatory process; absorption of bacteUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Tanrıkulu et al. Diagnostic utility of the neutrophil-lymphocyte ratio in patients with acute mesenteric ischemia

rial materials (including endotoxin) triggers inflammation that increases in extent as ischemia is prolonged, causing bacterial infiltration, sepsis, acidosis, septic shock, and, ultimately, death. During this process, inflammatory substances measurable in peripheral blood are released from necrotic cells of the gut wall.[2,6] Recent studies have focused on such materials because early and accurate detection of inflammation is essential in order to optimize treatment and prognosis of those with medical emergencies.[7] Several biomarkers, such as C-reactive protein (CRP), procalcitonin, and mean platelet volume (MPV) have been used as indicators of inflammation. Neutrophilia develops during inflammation, triggered by release of arachidonic acid metabolites and platelet activation. Such stress induces relative lymphopenia. Therefore, the neutrophil-lymphocyte ratio (NLR) accurately reflects underlying inflammatory processes.[8] Although several studies have explored the utility of NLR in the diagnosis and prognosis of inflammatory and malignant diseases, very rarely has NLR been used in the diagnosis of AMI.[9–11] In the present study, the diagnostic capacity of NLR was evaluated and compared to traditional parameters in such patients.

MATERIALS AND METHODS Study Groups and Study Design The present retrospective, cross-sectional, multi-center study was approved by the local ethics committee. A total of 58 AMI patients, 62 non-vascular bowel necrosis (NVBN) patients, and 62 control patients were enrolled. Each patient was treated in 1 of 3 hospitals: the Zonguldak Atatürk State Hospital, a 450-bed, 12-section, government-approved general hospital with high direct admission and referral rates, the Süleyman Demirel University Faculty of Medicine Hospital, a 400-bed, 14-section, government-approved general hospital with a high direct admission rate, or the Erzurum Regional Training and Research Hospital, a 700-bed, 18-section, government-approved general hospital with high direct admission and referral rates. Patients were enrolled between May 1, 2010 and April 30, 2015. Archived and electronically stored records were accessed. Patients who underwent laparotomies and/or bowel resections to treat AMI were included, as were NVBN patients who underwent segmental bowel excision to treat incarcerated and strangulated hernias. The control group included patients who presented to the emergency department with non-specific abdominal pain. Pre-study power analysis showed that the chosen sample size afforded a power of 0.9 for achievement of 95% confidence interval.

Complete Blood Count and Biochemical Analysis Biochemical tests and complete blood count (CBC) (on venous blood) were automated. CBC data from all 3 hospitals were similar to recognized international norms. White blood cell (WBC) count, MPV, and red cell distribution width Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

(RDW) were evaluated, and NLRs were calculated. Normal values of all parameters were reference figures accepted by hematology laboratories nationwide.

Statistical Analysis Statistical analyses were performed using SPSS software (version 19.0; SPSS Inc., Chicago, IL, USA). Data distribution was evaluated using the Kolmogorov-Smirnov test. Continuous variables were expressed as mean±SD and categorical variables as frequencies (percentages). Significance of each difference among continuous variables was explored using independent samples t-test or Mann-Whitney U test. Significance of each difference between categorical variables was compared using Pearson chi-squared test. Receiver operating characteristic (ROC) curve analysis was used to define optimal cut-offs of NLR and RDW, for which specificities, sensitivities, positive and negative predictive values (PPV, NPV), and overall accuracies were calculated. Youden index was used to optimize accuracies of all calculations. A p value of less than 0.05 was considered to reflect statistical significance.

RESULTS A total of 58 AMI, 62 NVBN, and 62 control patients were enrolled. Mean patient age did not differ significantly among groups, being 68.43, 66.43, and 63.38 years, respectively. Of the AMI patients, 31 (36.2%) were female and 37 (63.8%) male, 26 (41.9%) NVBN patients were female and 36 (58.1%) male, and 28 (45.2%) control patients were female and 34 (54.8%) male. Patient profiles differed somewhat among the 3 hospitals, reflecting local population densities and hospital capacities. Regarding affected bowels, segmental involvement was evident in 39 (67.2%) AMI patients, with complete involvement in 19 (32.8%). Forty-two (72.4%) patients exhibited only small bowel involvement, but 16 (27.6%) exhibited both small intestinal and colonic involvement. Segmental involvement was evident in all NVBN patients. Mortality rates were 51.7% in the AMI group and 4.8% in the NVBN group. WBC counts, CRP levels, RDWs, MPVs, and NLRs are shown in Figures 1–4, as well as in Table 1. WBC counts and CRP levels were significantly higher in the AMI group than in the other groups (p=0.028 vs the NVBN group; p<0.001 vs controls in terms of WBC count; p<0.001 vs the NVBN and control groups in terms of CRP). RDW was significantly higher in the AMI group (p=0.002). MPV did not differ among groups (p=0.181). NLR was significantly higher in the AMI group than in the control group (p<0.001). WBC, CRP level, and NLR (but not RDW, p=1.000) were significantly higher in the NVBN group than in the controls (p<0.001 for all). Sensitivities and specificities of CRP levels and CBC data used to distinguish controls from AMI patients, and ROC 345

Tanrıkulu et al. Diagnostic utility of the neutrophil-lymphocyte ratio in patients with acute mesenteric ischemia

red cell distribution width (%)

White blood cell (x109)

* *

25 20 15 10

Acute Non-vascular mesenteric ischemia bowel necrosis

Control

Acute Non-vascular mesenteric ischemia bowel necrosis

Figure 1. Distribution among groups of WBC counts.

Control

Figure 3. Distribution among groups of RDWs.

Neutrophil-to-lymphocyte ratio

C-reactive protein (mg/dL)

** 20

0 Acute Non-vascular mesenteric ischemia bowel necrosis

* **

Control

Acute Non-vascular mesenteric ischemia bowel necrosis

Control

Figure 2. Distribution among groups of CRP levels.

Figure 4. Distribution among groups of NLR ratios.

curve analysis data on WBC counts, RDWs, and NLRs are shown in Table 2 and Figure 5. Sensitivities, specificities, PPVs, and NPVs of WBC counts (>10x109/L) and CRP levels (>0.5 mg/dL) were 86.21%, 95.16%, 94.30%, and 88.10%, and 100%, 100%, 100%, and 100%, respectively. Sensitivities, specificities, PPVs, and NPVs of NLRs were 74.14%, 88.71%, 86%, and 78.60%. The same figures for RDWs were 48.28%,

88.71%, 80%, and 64.70%, respectively. Youden index values for WBC count, CRP, RDW, and NLR were 0.814, 1.000, 0.369, and 0.628, respectively. ROC analysis showed that WBC count, CRP level, RDW, and NLR cut-off values that afforded optimal sensitivities and specificities were 10.99x109/L (86–95%), 2.10 mg/dL (100–100%), 14.70% (48–89%), and 5.21 (74–89%), respectively. Areas under the

Table 1. Laboratory data from all groups

Acute mesenteric ischemia Non-vascular bowel necrosis Control (n=58) (n=62) (n=62)

White blood cell (x109/L)

16.38 (4.48–38.20)#,*

13.10 (4.20–23.90)*

C-reactive protein (mg/dL)

16.60 (3.20–63.20)

6.40 (0.10–33.00)

0.20 (0–2.10)

Red cell distribution width (%)

14.55 (11.10–22.10)¥

13.35 (11.60–35.40)

13.30 (11.60–34.60)

Mean platelet volume (fL) Neutrophil-to-lymphocyte ratio

*,£

8.28 (4.15–12.23)

8.67±1.47

8.50±1.37

8.93±1.03

8.16 (0.36–42.87)*

9.92 (0.75–38.00)*

2.68 (0.96–12.28)

p=0.028 vs. non-vascular bowel necrosis, *p<0.001 vs. control, £p<0.001 vs. non-vascular bowel necrosis, ¥p=0.002 vs. non-vascular bowel necrosis and control.

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Table 2. Overall accuracies afforded by laboratory parameters used to distinguish AMI patients from controls (%)

Sensitivity

Specificity

PPD

NPD

Cut-off

Youden’s Index

White blood cell

86.21

95.16

94.30

88.10

10.99

0.814

C-reactive protein

100

2.10

1.000

Red cell distribution width

48.28

88.71

64.70

14.70

0.369

Mean platelet volume

46.55

70.97

58.70

8.30

0.175

Neutrophil-to-lymphocyte ratio

74.14

88.71

78.60

5.21

0.628

NPV: Negative predictive value; PPD: Positive predictive value.

Table 3. Overall accuracies afforded by laboratory parameters used to distinguish AMI patients from NVBN patients (%)

Sensitivity

Specificity

PPD

NPD

Cut-off

Youden’s Index

White blood cell

67.24

C-reactive protein

89.66

66.13

68.30

14.50

0.334

72.58

75.40

88.20

8.50

0.622

Red cell distribution width Mean platelet volume

65.52

66.13

64.40

67.20

13.90

0.317

81.03

24.72

51.10

60.70

7.40

0.057

Neutrophil-to-lymphocyte ratio

50.00

66.13

58.60

7.85

0.161

NPV: Negative predictive value; PPD: Positive predictive value.

curves (AUCs) for WBC count, RDW, and NLR were 93.4%, 69.7%, and 81.9%, respectively. Sensitivities and specificities of CRP levels and CBC data used to distinguish NVBN and AMI patients, and ROC data on WBC counts, RDWs, and NLRs, are shown in Table 3 and Figure 6. Sensitivities, specificities, PPVs, and NPVs of WBC counts (>10x109/L) and CRP levels (>0.5 mg/dL) were 67.24%, 66.13%, 65%, and 68.30%, and 89.66%, 72.58%, 75.40%, and

88.20%, respectively. Sensitivities, specificities, PPVs, and NPVs of NLRs were 50%, 66.13%, 58%, and 58.60%, respectively. Those of RDWs were 65.52%, 66.13%, 64.40%, and 67.20%, respectively. Youden index values for WBC count, CRP level, RDW, and NLR were 0.334, 0.622, 0.317, and 0.161, respectively. ROC analysis showed that WBC count, CRP level, RDW, and NLR cut-off values affording the best sensitivities and specificities were 14.50x109/L (67–66%), 8.50 mg/dL (90–73%), 13.90% (66–66%), and 7.85% (50–66%),

0.8

Sensitivity

1.0

Sensitivity

1.0

0.6

0.4

0.2

WBC RDW NLR

0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 5. ROC curve used to distinguish AMI patients from controls.

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0.2

WBC RDW NLR

0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 6. ROC curve used to distinguish AMI from NVBN patients.

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Tanrıkulu et al. Diagnostic utility of the neutrophil-lymphocyte ratio in patients with acute mesenteric ischemia

respectively. AUCs for WBC count, RDW, and NLR were 67.4%, 67%, and 47.4%, respectively.

DISCUSSION It was presently determined that NLR was highly sensitive and specific when used to identify patients with AMI (an abdominal emergency with a high mortality rate). Differential diagnosis of AMI must be urgently performed. Mean age of AMI patients exceeds 65 years.[12] Kougias et al.[13] reported a mean age of 71 years; the mean age of our AMI group was 68.43 years. Early diagnosis and treatment of AMI are essential in the prevention of irreversible damage to the bowel wall.[14,15] Any diagnosis that begins with a suspicion raised by clinical findings should be confirmed by laboratory and imaging methods. Clinical presentation of AMI is highly varied. Classically, the condition is associated with dramatic-onset severe abdominal pain, disproportionate to findings on physical examination. However, early correct diagnosis is often difficult, as many AMI signs and symptoms are shared by other emergency intra-abdominal pathologies, including appendicitis, pancreatitis, small intestine obstruction, and acute diverticulitis.[1,16] Such problems have encouraged researchers to devise new laboratory and imaging methods. As AMI is an inflammatory process, intense effort has been devoted to the definition of specific early biochemical and serological markers of such inflammation.[17] However, useful markers are few. Classically, AMI patients exhibit leukocytosis, metabolic acidosis, and elevated levels of serum D-dimer and lactate.[18] Although the leukocytosis is significant, it has been reported as unhelpful in differential diagnosis.[1] However, in the retrospective study of Paladino et al.,[19] leukocytosis was a significant diagnostic and prognostic factor. In the present study, profound leukocytosis was evident in AMI patients (p<0.001). Other useful parameters are D-dimer and serum lactate levels.[1] These levels were not measured in the present patients. NLR is a simple biomarker of inflammation. Total leukocyte and neutrophil counts have traditionally been considered markers of infection. Associations are evident between monocyte and lymphocyte counts, as well as between these counts and infection.[7,20] During inflammation, neutrophil counts increase as lymphocyte counts decrease, controlled by neurohormonal mechanisms. Therefore, NLR accurately reflects underlying inflammatory processes.[8] NLR is increasingly used to predict the survival of patients with malignancies, coronary artery disease, acute appendicitis, acute cholecystitis, acute pancreatitis, and community-acquired infections.[7] Lee et al.[21] found that preoperative NLR accurately predicted the development of severe cholecystitis. Yu et al.[22] found that preoperative NLR was prognostic for gastric cancer patients. Suppiah et al.[23] found that NLR elevation during the first 48 hours of admission was significantly 348

associated with severe acute pancreatitis, and was an independent (negative) prognostic factor. Kahramanca et al.[24] found preoperative NLR useful in the diagnosis of acute appendicitis, as well as in the differentiation of patients with simple and complicated appendicitis. Aktimur et al.[11] found high NLR (<9.99) valuable in AMI diagnosis. In addition, RDW was higher in AMI patients than in those with acute appendicitis, and MPV was higher in AMI patients than in controls. In the present study, NLRs were higher in the AMI and NVBN groups than in the control group (p<0.001). However, no difference was found between the AMI and NVBN groups in this respect (p=1.000). Unlike the findings of Aktimur et al.,[11] the present MPVs were similar in all groups (p=0.181). RDWs were higher in the AMI group than in the other groups (p=0.002), but did not differ between the NVBN and control groups (p=1.000). In terms of AMI diagnosis, sensitivity of 80% and specificity of 50% was afforded by WBC count; the same figures for the NLR were 69% and 71%.[2,11] In an earlier study[25] of RDW in the context of diagnosing AMI, cut-off value, sensitivity, and specificity were 15.04%, 40.8%, and 81.2%, respectively. Another study[26] found that the AUC for RDW was 0.713, and that the cut-off value was 14.85%. Sensitivities, specificities, PPVs, and NPVs for WBC count, RDW, and NLR were 86.21%, 95.14%, 94.30%, and 88.10%; 48.28%, 88.71%, 80%, and 64.70%; and 74.14%, 88.71%, 86%, and 78.60%, respectively. RDW and NLR data were consistent with published findings, but WBC count figures were higher. ROC analysis yielded cut-offs for WBC count, RDW, and NLR, as well as for optimal sensitivities and specificities. These were 14.50x109/L (67–66%), 13.90% (66–66%), and 7.85 (50–66%), respectively. In conclusion, preoperative NLR aids in the diagnosis of AMI, differentiating the condition from NVBN, and can be used as an adjunct to clinical examination. Conflict of interest: None declared.

REFERENCES 1. van den Heijkant TC, Aerts BA, Teijink JA, Buurman WA, Luyer MD. Challenges in diagnosing mesenteric ischemia. World J Gastroenterol 2013;19:1338–41. 2. Evennett NJ, Petrov MS, Mittal A, Windsor JA. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J Surg 2009;33:1374–83. 3. Karabulut K, Gül M, Dündar ZD, Cander B, Kurban S, Toy H. Diagnostic and prognostic value of procalcitonin and phosphorus in acute mesenteric ischemia. Ulus Travma Acil Cerrahi Derg 2011;17:193–8. 4. Hamzaoğlu I, Ulualp K, Balkan T, Şirin F. Abdominal emergencies in octogenerians. Ulus Travma Acil Cerrahi Derg 2000;6:36–8. 5. Demir IE, Ceyhan GO, Friess H. Beyond lactate: is there a role for serum lactate measurement in diagnosing acute mesenteric ischemia?. Dig Surg 2012;29:226–35. 6. Klar E, Rahmanian PB, Bücker A, Hauenstein K, Jauch KW, Luther B. Acute mesenteric ischemia: a vascular emergency. Dtsch Arztebl Int 2012;109:249–56.

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Tanrıkulu et al. Diagnostic utility of the neutrophil-lymphocyte ratio in patients with acute mesenteric ischemia 7. de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 2010;14:R192. 8. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol 2008;102:653–7. 9. Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-lymphocyte ratio has a close association with gangrenous appendicitis in patients undergoing appendectomy. Int Surg 2012;97:299–304. 10. Azab B, Jaglall N, Atallah JP, Lamet A, Raja-Surya V, Farah B, et al. Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis. Pancreatology 2011;11:445–52. 11. Aktimur R, Cetinkunar S, Yildirim K, Aktimur SH, Ugurlucan M, Ozlem N. Neutrophil-to-lymphocyte ratio as a diagnostic biomarker for the diagnosis of acute mesenteric ischemia. Eur J Trauma Emerg Surg 2015. 12. Gün B, Yolcu S, Değerli V, Elçin G, Tomruk Ö, Erdur B, et al. Multidetector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients. Ulus Travma Acil Cerrahi Derg 2014;20:376–81. 13. Kougias P, Lau D, El Sayed HF, Zhou W, Huynh TT, Lin PH. Determinants of mortality and treatment outcome following surgical interventions for acute mesenteric ischemia. J Vasc Surg 2007;46:467–74. 14. Öz B, Akyüz M, Emek E, Sözüer E, Akyıldız H, Akcan A, et al. The effectiveness of gastric tonometry in the diagnosis of acute mesenteric ischemia in cases where a contrast-enhanced computed tomography cannot be obtained. Ulus Cerrahi Derg 2014;31:26–9. 15. Bradbury AW, Brittenden J, McBride K, Ruckley CV. Mesenteric ischaemia: a multidisciplinary approach. Br J Surg 1995;82:1446–59. 16. Wyers MC. Acute mesenteric ischemia: diagnostic approach and surgical treatment. Semin Vasc Surg 2010;23:9–20.

17. Gönüllü D, Yankol Y, Işiman F, Akyildiz Iğdem A, Yücel O, Köksoy FN. pH value and potassium level of diagnostic peritoneal lavage fluid in the early diagnosis of acute mesenteric ischemia secondary to arterial occlusion in rats. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2007;13:261–7. 18. Oldenburg WA, Lau LL, Rodenberg TJ, Edmonds HJ, Burger CD. Acute mesenteric ischemia: a clinical review. Arch Intern Med 2004;164:1054– 62. 19. Paladino NC, Inviati A, Di Paola V, Busuito G, Amodio E, Bonventre S, et al. Predictive factors of mortality in patients with acute mesenteric ischemia. A retrospective study. Ann Ital Chir 2014;85:265–70. 20. Wyllie DH, Bowler IC, Peto TE. Relation between lymphopenia and bacteraemia in UK adults with medical emergencies. J Clin Pathol 2004;57:950–5. 21. Lee SK, Lee SC, Park JW, Kim SJ. The utility of the preoperative neutrophil-to-lymphocyte ratio in predicting severe cholecystitis: a retrospective cohort study. BMC Surg 2014;14:100. 22. Yu L, Lv CY, Yuan AH, Chen W, Wu AW. Significance of the preoperative neutrophil-to-lymphocyte ratio in the prognosis of patients with gastric cancer. World J Gastroenterol 2015;21:6280–6. 23. Suppiah A, Malde D, Arab T, Hamed M, Allgar V, Smith AM, et al. The prognostic value of the neutrophil-lymphocyte ratio (NLR) in acute pancreatitis: identification of an optimal NLR. J Gastrointest Surg 2013;17:675–81. 24. 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. 25. Kisaoglu A, Bayramoglu A, Ozogul B, Atac K, Emet M, Atamanalp SS. Sensitivity and specificity of red cell distribution width in diagnosing acute mesenteric ischemia in patients with abdominal pain. World J Surg 2014;38:2770–6. 26. Bilgiç I, Dolu F, Şenol K, Tez M. Prognostic significance of red cell distribution width in acute mesenteric ischemia. Perfusion 2015;30:161–5.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut mezenterik iskemili hastalarda nötrofil-lenfosit oranının tanısal yararı: Geriye dönük kohort çalışma Dr. Yusuf Tanrıkulu,1 Dr. Ceren Şen Tanrıkulu,2 Dr. Mehmet Zafer Sabuncuoğlu,3 Dr. Ayetullah Temiz,4 Dr. Furuzan Köktürk,5 Dr. Boran Yalçın1 Zonguldak Atatürk Devlet Hastanesi, Genel Cerrahi Kliniği, Zonguldak Bülent Ecevit Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Zonguldak 3 Süleyman Demirel Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Isparta 4 Erzurum Bölge Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Erzurum 5 Bülent Ecevit Üniversitesi Tıp Fakültesi, Bioistatistik Anabilim Dalı, Zonguldak 1 2

AMAÇ: Akut mezenterik iskemi (AMI) olgularının %50–70’i ölümcül olup, hızlı ve etkili bir klinik değerlendirme ve tedavi gerektiren bir vasküler acil olarak kabul edilmektedir. Mevcut geriye dönük çalışmada, biz AMI erken tanısında nötrofil/lenfosit oranının (NLR) olası yararını ve bu oranın AMI ile non-vasküler bağırsak nekrozu (NVBN) ayırıcı tanısında etkili olup olmadığını araştırdık. GEREÇ VE YÖNTEM: Bu çalışmada 1 Mayıs 2010–30 Nisan 2015 tarihleri arasında 58 AMI, 62 NVBN ve 62 kontrol hastası incelendi. Akut mezenterik iskemi tanısıyla laparotomi ve/veya bağırsak rezeksiyonu yapılan hastalar çalışma grubuna alındı. İnkarsere ve strangüle herni nedeniyle segmenter bağırsak rezeksiyonu yapılan hastalar NVBN grubuna alındı. Kontrol grubu hastaları non-spesifik karın ağrısı nedeniyle acil servise başvuran hastalarda oluşturuldu. BULGULAR: Mortalite oranı AMI grubunda %51.7, NVBN grubunda %4.8 idi. Akut mezenterik iskemi grubunda lökosit (WBC) sayısı, C-reaktif protein (CRP) ve eritrosit dağılım aralığı diğer gruplardan daha yüksekti. Nötrofil/lenfosit oranı, AMI ve NVBN grubunda kontrol grubundan daha yüksekti (p<0.001), ancak AMI ve NVBN grupları arasında fark yoktu. Ayrıca, NVBN grubunda WBC sayısı ve CRP control grubundan daha yüksekti (p<0.001). TARTIŞMA: Ameliyat öncesi NLR düzeyinin AMI tanısında yardımcı olacağını ve AMI ile bağırsak nekrozu ile seyreden NVBN gibi durumlarla ayrıcı tanıda kullanabileceğini düşünmekteyiz. Bundan dolayı, bu tür hastalarda NLR klinik muayeneye ek olarak hesaplanmalıdır. Anahtar sözcükler: Akut mezenterik iskemi; NLR; serum belirteçleri; tanı. Ulus Travma Acil Cerrahi Derg 2016;22(4):344–349

doi: 10.5505/tjtes.2015.28235

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ORIGIN A L A R T IC L E

Medial mini-open versus percutaneous pin fixation for type III supracondylar fractures in children Ersin Erçin, M.D.,1 Mustafa Gökhan Bilgili, M.D.,1 Emre Baca, M.D.,1 Serdar Hakan Başaran, M.D.,2 Alkan Bayrak, M.D.,1 Cemal Kural, M.D.,1 Mustafa Cevdet Avkan, M.D.1 1

Department of Orthopaedics and Traumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

Department of Orthopaedics and Traumatology, Karabük University Faculty of Medicine, Zonguldak-Turkey

ABSTRACT BACKGROUND: The present objective was to compare medial mini-open and percutaneous treatment of pediatric supracondylar fractures according to fluoroscopy time, duration of surgery, and iatrogenic ulnar nerve injury. METHODS: A total of 104 Gartland type III supracondylar humerus fractures were prospectively evaluated between 2011 and 2013. Patients were divided into 2 groups according to type of fixation. In Group A (41 patients), medial pin was inserted with mini-open incision with 2 lateral pins inserted percutaneously. In Group B (63 patients), all pins were inserted percutaneously. Mean follow-up time was 14.1±1.2 months in Group A, and 14.6±2.1 months in Group B. All patients were postoperatively evaluated for nerve injury with both motor and sensory function assessment. Length of surgery, total fluoroscopy time, fluoroscopy time for medial pin insertion, Baumann’s angle, humeral capitellum angle, final carrying angle, and range of motion were recorded. RESULTS: Sensorial evaluation showed that Group A had 3 poor, and 1 fair results, and Group B had 2 poor, and 1 fair results. No statistically significant differences were observed, including no differences in either surgery or total fluoroscopy times between groups. However, fluoroscopy time during medial pin placement was significantly lower in the mini-open group. CONCLUSION: In conclusion, similar results of both techniques were observed, and both carry risk of iatrogenic ulnar nerve injury. Medial pin placement is easier and less demanding when used with mini-open technique. Keywords: Fracture; humerus; pediatric; supracondylar fracture; ulnar nerve.

INTRODUCTION Supracondylar humerus fractures are those most likely to require surgery in children.[1,2] Closed reduction and percutaneous pin fixation are the current treatment modalities. The primary disadvantages of the percutaneous technique are ulnar nerve injury and prolonged use of fluoroscopy.[3] In the literature, incidence of ulnar nerve palsy ranges from 0–14.3% after closed pinning.[4–8] Due to this risk, some authors advocate only lateral pin placement, while others advoThis study presented in part as an oral presentation of free paper at the 17th European Federation of National Associations of Orthopaedics and Traumatology Congress (Geneva, Switzerland, June 01–03, 2016).

Address for correspondence: Ersin Erçin, M.D. Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul, Turkey Tel: +90 212 - 414 23 32 E-mail: ersine@hotmail.com Qucik Response Code

350

cate medial mini-open technique.[9,10] However, whether miniopen approach is necessary to avoid iatrogenic ulnar nerve injury has yet to clarified. Fluoroscopy usage is essential for closed reduction and percutaneous K-wire fixation of supracondylar fractures, yet few studies have addressed radiation exposure in displaced supracondylar humeral fractures. In a recent study, authors concluded that surgeons were exposed to direct radiation beam a median of 13% of surgery duration.[11] The present objective was to compare medial mini-open and percutaneous treatments of pediatric supracondylar fractures by fluoroscopy time, surgery duration, and occurrence of iatrogenic ulnar nerve injury.

MATERIALS AND METHODS A total of 132 Gartland type III supracondylar humerus fractures were treated with closed reduction and crossed K-wire fixation between 2011 and 2013. Informed consent was obtained from patients and from the ethics committee. Inclusion criteria were patients with Gartland type III fracUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Erçin et al. Medial mini-open versus percutaneous pin fixation for type III supracondylar fractures in children

tures who had 2 lateral and 1 medial pins placed during surgery. Patients with preoperative neurovascular injuries, open fractures, previous ipsilateral elbow fractures, or flexion fractures were excluded. Specifically, 3 patients with flexion fractures, 3 with open fractures, 4 with preoperative nerve paralysis (2 median, 1 ulnar, 1 radial nerve), 1 who had undergone previous surgery for olecranon fracture, 2 who did not attend final examination, and 15 patients who had undergone only 1 lateral and medial pin fixation were excluded from the study.

epicondyle. Superficial dissection was performed to ensure that the pin had been placed in the medial epicondyle and that the ulnar nerve was not anteriorly subluxated over the medial epicondyle. The medial pin was then placed in extended arm position, starting from the medial epicondyle to the lateral cortex. Then, another lateral pin was inserted percutaneously across the lateral cortex to the medial cortex. In Group B (63 patients), all pins were inserted percutaneously from the lateral side with the same order.

A total of 104 patients were included. Patients were divided into 2 groups according to type of fixation: medial mini-open (Group A) and percutaneous (Group B). Four attending physicians treated the patients, while residents under the supervision of an attending physician performed some surgical procedures. Children were randomized based on which orthopedic surgeon was on trauma call: 2 surgeons (M.G.B., E.E.) used medial mini-open technique (on patients in Group A), while the others (E.B., S.H.B.) used percutaneous technique, (on patients in Group B). The same pin configuration– lateral divergent 2 pins and 1 crossed medial pin– was used. All patients underwent surgery under general anesthesia with closed reduction by fluoroscopic control in supine position.

During surgery, total fluoroscopy time and fluoroscopy time for medial pin insertion were measured. After fixation of the fracture, pins bended outside the skin, and posterior long-arm splints were applied in the neutral position. Pins were removed after 3–4 weeks. All patients were clinically and radiologically evaluated at 1 week, 4 weeks, 3 months, and 6 months. Evaluation consisted of assessment of the carrying angle, measurement of range of motion of the elbow, and neurologic examination. All patients were evaluated for nerve injury with both motor and sensory function assessments. Sensory assessments were made by Semmes-Weinstein monofilament test and static 2-point discrimination test. Monofilament 2.83 was considered normal, and in static 2-point discrimination, <6 mm was considered normal, 6–10 mm was considered fair, and 10–15 mm was considered poor.[12]

In Group A (41 patients), 1 pin was inserted percutaneously from the lateral aspect of the elbow across the lateral cortex to the medial cortex, with the elbow in hyperflexion, before a small medial incision of 1–1.5 cm was made over the medial

In radiographic evaluation, anteroposterior and lateral radiography of the elbow was assessed by 2 researchers (E.E. and

Table 1. Patients data No. of patients Age (year)

Medial mini-open incision

All percutaneous group

6.2±2.65

6.67±3.11

Sex

0.425

0.946

Male

Female

Side 0.082 Right

Left

Mono Filament Normal

Fair

Poor Time from trauma to surgery (hour)

3 17.15±6.67

0.593

2 15.1±6.77

0.132

Fluoroscopy time for medial pin (second)

8.85±3.07

10.52±3.39

0.012

Fluoroscopy time for lateral pin (second)

32.76±6.07

30.94±6.85

0.01

Total fluoroscopy time (second)

41.61±9.25

41.46±10.03

0.939

Anesthesia time (minutes)

47.71±14.44

53.56±21.83

0.134

Hospitalization time (day)

2.2±1.12

1.98±1.29

0.393

Pin removal time (day)

30.8±5.93

30.33±5.74

0.687

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Erçin et al. Medial mini-open versus percutaneous pin fixation for type III supracondylar fractures in children

M.G.B.). Baumann angle was measured on the anteroposterior radiograph of the elbow at 3-month follow-up. Humerocapitellar angle was measured at the lateral elbow radiograph. Single-measure intraclass correlation coefficient was used for continuous variables, while Cohen kappa coefficient was used for categorical variables. Good interobserver agreement (0.6–0.8) was found for all continuous variables, and almost perfect agreement (>0.8) was found for all categorical variables. Carrying angle was measured by full-circle goniometer and compared with the contralateral arm. NCSS statistics software (2007; NCSS, LLC., Kaysville, Utah, USA) was used for statistical analysis. Statistical comparisons among groups were made with the Mann-Whitney U-test, Pearson’s chi-squared test, and independent samples t-test. A p value <0.05 was accepted as significant.

RESULTS Demographic characteristics and surgical properties are shown in Table 1. No significant differences were found (p>0.05) between groups regarding Baumann angle, humerocapitellar angle, carrying angle, elbow extension, or elbow flexion. Patients were compared according to hospitalization time, pin removal, C-arm time for medial pin placement, total fluoroscopy time, and anesthesia time. Hospitalization time, pin removal time, total fluoroscopy time, and anesthesia time showed no significant difference. However, fluoroscopy time for medial pin placement was significantly shorter in Group A (p=0.012), while lateral pin placement time was significantly shorter in Group B (p=0.01) (Table 1). All patients had normal motor function at postoperative firstweek control. According to monofilament test, all patients had normal, 2.83 results. However, on static 2-point discrimination test, Group A included 3 poor, and 1 fair results, while Group B included 2 poor, and 1 fair results (<6 mm was considered normal, 6–10 mm was considered fair, 10–15 mm was considered poor). No significant difference was found, regarding these results. (p=0.593). All patients had complete return of nerve function and full movement of the elbow at 6-month follow-up. No alteration was made to treatment of patients with poor or fair results; no reduction loss was observed during follow-up. All incisions in the mini-open group healed without complication. Pin site infection occurred in 2 (4.9%) patients in Group A, and 3 (4.8%) patients in Group B. Oral antibiotics were used in all cases. No significant difference in occurrence of infection was observed between groups (p>0.05). No deep infection or osteomyelitis occurred.

DISCUSSION Surgical treatment of displaced supracondylar humeral fractures consists of open or closed reduction with K-wire 352

fixation. Closed reduction and percutaneous fixation with crossed K-wires shows successful results. However, debate persists regarding optimal pin fixation technique. Biomechanical studies suggest that medial and lateral crossed K-wire fixation is the most stable.[13,14] Some authors assert the importance of an additional medial K-wire to prevent reduction loss.[15,16] Incidence of iatrogenic nerve injury of 14.3% was recently reported in surgically treated cases of supracondylar humerus fracture. In the same study, the ulnar nerve was reported as that most commonly injured (82.1%), followed by the radial (7.7%) and median (5.1%) nerves.[5] In a randomized prospective study, the ulnar nerve was injured in 3 of 557 (0.53%) cases with laterally introduced pins. Medially introduced pins resulted in ulnar nerve injury in 49 of 808 (6%) cases. The same authors found a 21% rate of reduction loss in cases of laterally placed pins. Medial and lateral pin placement had a significantly lower reduction loss rate of 4%.[10] In spite of biomechanical advantages to medial and lateral crossed wire fixation, ulnar nerve injury is a potential complication of medial pin placement. In order to reduce the risk of ulnar nerve palsy, several precautions are suggested, including making a small incision over the medial epicondyle for direct visualization.[17] However, it is not clear whether a mini-incision technique can prevent iatrogenic ulnar nerve injury. Although visualizing the ulnar nerve via a small incision prior to pin placement is theoretically less risky, ulnar nerve lesions are usually caused by the prevention of normal anterior translation to the ulnar nerve, rather than penetrations of the nerve.[18] In 2 studies in which lateral-pin and crossedpin medial mini-open techniques were compared, no iatrogenic ulnar nerve injury was reported in either group. Both techniques were determined to be effective for treatment of supracondylar humerus fractures.[10,19] In a meta-analysis of randomized controlled trials, crossedpinning fixation was determined to carry greater risk of iatrogenic ulnar nerve injury than lateral pinning, and the later technique was recommended.[20] In a single retrospective cohort study that included 65 patients (29 Gartland type III and 36 Gartland type II fractures), authors reported 1 iatrogenic ulnar nerve injury and recommended crossed-pin fixation with mini-open technique as a safe and reliable method. [4] The present is the first study to compare medial mini-open crossed-pinning and percutaneous crossed-pinning techniques. No significant difference in incidence of ulnar nerve injury was found between the techniques (p=0.593). Initial neurovascular examination is vital in determining whether injury is the result of fracture displacement or surgical complication. The importance of preoperative neurologic examination was emphasized in a recent study, as was the potential for preoperative neurologic deficit to be missed in initial management.[21] Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Erçin et al. Medial mini-open versus percutaneous pin fixation for type III supracondylar fractures in children

Ulnar nerve injury results in numbness of the little finger and the ulnar half of the ring finger. Sensory disturbance can be evaluated with threshold tests (such as the monofilament test). Alterations in sensory conduction are more sensitive indicators of nerve injury and found to correlate more directly with physical examination findings.[22] In the present patients, monofilament test was conducted at 1 postoperative week. Group A had 3 poor and 1 fair results, while Group B had 2 poor and 1 fair results. No significant difference was observed. No patient had neurologic deficit in hand movement on physical examination. All sensory deficits were resolved at 6-month follow-up. While fluoroscopy usage is essential, radiation exposure is a risk.[23,24] Few reports have addressed fluoroscopy time of supracondylar humeral fracture surgery. In a study comparing open reduction and internal fixation with closed reduction and internal fixation in Gartland type III supracondylar fractures, surgery and fluoroscopy times were significantly longer in the closed reduction and fixation group.[3] In another study of supracondylar humerus fractures, fluoroscopy time increased when closed reduction was intraoperatively switched to open reduction. The authors suggested that radiation exposure time be a factor when selecting surgical approach in prolonged closed reduction surgeries.[25] The present surgery and fluoroscopy times were consistent with others reported. [3,25] In theory, open incision should have additional risk of morbidity, though there is no evidence that medial incision in mini-open technique causes additional healing problems. This may be due to the small incision size and minimal dissection required. No differences in healing were presently observed between the groups. No significant difference in surgery or fluoroscopy times were observed between groups. However, fluoroscopy usage during medial pinning was significantly lower in the mini-open group. This may be due to clearer identification of medial epicondyle and easier pin placement, without ulnar nerve concern. Small population size and short follow-up period were the present limitations, in addition to the method of randomization used. Although a randomized clinical trial would be ideal, an extremely large study group would be needed to assess iatrogenic ulnar nerve injury. It was concluded in a systematic review that a minimum of 1000 patients would be needed to determine difference in complication rates (α=0.05, β=0.8, difference to detect=0.035).[16] It was concluded in another review that a sample size of 2000 patients would be needed according to 1.6% difference (α=0.05, β=0.20, power=80%) in cases of iatrogenic ulnar nerve injury, and the difficulties inherent in conducting such an investigation were emphasized.[26] Given the near impossibility of conducting such large prospective randomized studies, surgeon-randomized trials retain their value in the comparison of surgical treatment Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

methods of supracondylar humerus fractures.[27–29] In surgeon randomization, there is the risk that the surgeon may choose the mini-open technique if unable to palpate the ulnar nerve due to swelling. Rates of iatrogenic ulnar nerve injury would have been higher if the percutaneous technique had also been used in this group of patients. The present study was the first to evaluate neurologic deficiency with monofilament test after surgical treatment of supracondylar humerus fractures. Similar surgery times show that the mini-open technique does not increase surgery time. All fractures united without radiological or clinical complications after 6 postoperative months. Ulnar nerve injury occurred in 7.3% of Group A patients, and in 3.2% of those in Group B. That this difference was not statistically significant may be due to palpation of the ulnar nerve during protection attempts. In conclusion, medial mini-open technique had similar results to percutaneous technique; both carry the risk of iatrogenic ulnar nerve injury. Medial pin placement without injury is still a challenge in pediatric supracondylar humerus fracture surgery. Aside from the additional morbidity risk of mini-open incision, medial pin placement is easier and less demanding in mini-open technique.

Compliance With Ethical Requirements The authors declare that they have no conflict of interest. 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 was obtained from all individual participants included in the study. Local institutional review board approval was also obtained. Conflict of interest: None declared.

REFERENCES 1. Carson S, Woolridge DP, Colletti J, Kilgore K. Pediatric upper extremity injuries. Pediatr Clin North Am 2006;53:41–67. 2. Omid R, Choi PD, Skaggs DL. Supracondylar humeral fractures in children. J Bone Joint Surg Am 2008;90:1121–32.. 3. Esen E, Doğramaci Y, Gültekin S, Görmeli G, Yildirim A, Kanatli U, et al. Comparison of radiation exposure times in the treatment of pediatric supracondylar humeral fractures with open-closed reduction and internal fixation. [Article in Turkish] Acta Orthop Traumatol Turc 2009;43:400–5. 4. Gordon JE, Patton CM, Luhmann SJ, Bassett GS, Schoenecker PL. Fracture stability after pinning of displaced supracondylar distal humerus fractures in children. J Pediatr Orthop 2001;21:313–8. 5. Khademolhosseini M, Abd Rashid AH, Ibrahim S. Nerve injuries in supracondylar fractures of the humerus in children: is nerve exploration indicated? J Pediatr Orthop B 2013;22:123–6. 6. Kumar R, Kiran EK, Malhotra R, Bhan S. Surgical management of the severely displaced supracondylar fracture of the humerus in children. Injury 2002;33:517–22. 7. Mostafavi HR, Spero C. Crossed pin fixation of displaced supracondylar humerus fractures in children. Clin Orthop 2000;376:56–61.

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Erçin et al. Medial mini-open versus percutaneous pin fixation for type III supracondylar fractures in children 8. Shim JS, Lee YS. Treatment of completely displaced supracondylar fracture of the humerus in children by cross-fixation with three Kirschner wires. J Pediatr Orthop 2002;22:12–6. 9. Skaggs DL, Hale JM, Bassett J, Kaminsky C, Kay RM, Tolo VT. Operative treatment of supracondylar fractures of the humerus in children. The consequences of pin placement. J Bone Joint Surg Am 2001;83–A:735– 40. 10. Kocher MS, Kasser JR, Waters PM, Bae D, Snyder BD, Hresko MT, et al. Lateral entry compared with medial and lateral entry pin fixation for completely displaced supracondylar humeral fractures in children. A randomized clinical trial. J Bone Joint Surg Am 2007;89:706–12. 11. Eismann EA, Wall EJ, Thomas EC, Little MA. Direct beam radiation exposure to surgeons during pinning of supracondylar humerus fractures: does C-arm position and the attending surgeon matter? J Pediatr Orthop 2014;34:166–71. 12. Lundborg G, Rosén B. The two-point discrimination test--time for a reappraisal? J Hand Surg Br 2004;29:418–22. 13. Pretell-Mazzini J, Rodriguez-Martin J, Andres-Esteban EM. Does open reduction and pinning affect outcome in severely displaced supracondylar humeral fractures in children? A systematic review. Strategies Trauma Limb Reconstr 2010;5:57–64. 14. Zamzam MM, Bakarman KA. Treatment of displaced supracondylar humeral fractures among children: crossed versus lateral pinning. Injury 2009;40:625–30. 15. Pretell-Mazzini J, Rodriguez-Martin J, Auñon-Martin I, Zafra-Jimenez JA. Controversial topics in the management of displaced supracondylar humerus fractures in children. Strategies Trauma Limb Reconstr 2011;6:43–50. 16. Slobogean BL, Jackman H, Tennant S, Slobogean GP, Mulpuri K. Iatrogenic ulnar nerve injury after the surgical treatment of displaced supracondylar fractures of the humerus: number needed to harm, a systematic review. J Pediatr Orthop 2010;30:430–6. 17. Brown IC, Zinar DM. Traumatic and iatrogenic neurological complications after supracondylar humerus fractures in children. J Pediatr Orthop 1995;15:440–3. 18. Lee SS, Mahar AT, Miesen D, Newton PO. Displaced pediatric supracondylar humerus fractures: biomechanical analysis of percutaneous pinning techniques. J Pediatr Orthop 2002;22:440–3.

19. Maity A, Saha D, Roy DS. A prospective randomised, controlled clinical trial comparing medial and lateral entry pinning with lateral entry pinning for percutaneous fixation of displaced extension type supracondylar fractures of the humerus in children. J Orthop Surg Res 2012;7:6. 20. Zhao JG, Wang J, Zhang P. Is lateral pin fixation for displaced supracondylar fractures of the humerus better than crossed pins in children? Clin Orthop Relat Res 2013;471:2942–53. 21. Joiner ER, Skaggs DL, Arkader A, Andras LM, Lightdale-Miric NR, Pace JL, et al. Iatrogenic nerve injuries in the treatment of supracondylar humerus fractures: are we really just missing nerve injuries on preoperative examination? J Pediatr Orthop 2014;34:388–92. 22. Shin R, Ring D. The ulnar nerve in elbow trauma. J Bone Joint Surg Am 2007;89:1108–16. 23. Bahari S, Morris S, Broe D, Taylor C, Lenehan B, McElwain J. Radiation exposure of the hands and thyroid gland during percutaneous wiring of wrist and hand procedures. Acta Orthop Belg 2006;72:194–8. 24. Perisinakis K, Damilakis J, Theocharopoulos N, Papadokostakis G, Hadjipavlou A, Gourtsoyiannis N. Patient effective dose and radiogenic risks from fluoroscopically assisted surgical reconstruction of femoral fractures. Radiat Prot Dosimetry 2004;108:65–72. 25. Kraus R, Joeris A, Castellani C, Weinberg A, Slongo T, Schnettler R. Intraoperative radiation exposure in displaced supracondylar humeral fractures: a comparison of surgical methods. J Pediatr Orthop B 2007;16:44–7. 26. Brauer CA, Lee BM, Bae DS, Waters PM, Kocher MS. A systematic review of medial and lateral entry pinning versus lateral entry pinning for supracondylar fractures of the humerus. J Pediatr Orthop 2007;27:181–6. 27. Kwak-Lee J, Kim R, Ebramzadeh E, Silva M. Is medial pin use safe for treating pediatric supracondylar humerus fractures? J Orthop Trauma 2014;28:216–21. 28. Tripuraneni KR, Bosch PP, Schwend RM, Yaste JJ. Prospective, surgeon-randomized evaluation of crossed pins versus lateral pins for unstable supracondylar humerus fractures in children. J Pediatr Orthop B 2009;18:93–8. 29. Gaston RG, Cates TB, Devito D, Schmitz M, Schrader T, Busch M, et al. Medial and lateral pin versus lateral-entry pin fixation for Type 3 supracondylar fractures in children: a prospective, surgeon-randomized study. J Pediatr Orthop 2010;30:799–806.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Çocuk tip III suprakondiler humerus kırıklarında medial mini açık teknikle perkütan tekniğin karşılaştırlması Dr. Ersin Erçin,1 Dr. Mustafa Gökhan Bilgili,1 Dr. Emre Baca,1 Dr. Serdar Hakan Başaran,2 Dr. Alkan Bayrak,1 Dr. Cemal Kural,1 Dr. Mustafa Cevdet Avkan1 1 2

Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul Karabük Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Kliniği, Zonguldak

AMAÇ: Bu çalışmada, çocukluk çağında görülen suprakondiler humerus kırıklarında medial mini açık teknikle perkütan tekniği karşılaştırıldı, floroskopi zamanı, cerrahi süre ve iyatrojenik ulnar sinir hasarı araştırıldı. GEREÇ VE YÖNTEM: 2011 ve 2013 yılları arasında ameliyat edilen 104 adet Gartland tip III suprakondiler humerus kırığı ileriye yönelik olarak incelendi. Birinci gruptaki (Grup A) 41 hastaya medial mini açık insizyonla medialden bir ve lateralden iki adet pin ile fiksasyonu yapıldı. İkinci gruptaki (Grup B) 63 hastaya tüm pinler perkütan yerleştirildi. Ortalama takip süresi Grup A’da 14.1±1.2 ay ve Grup B’de 14.6±2.1 aydır. Cerrahi sonrası hastalar sinir yaralanması açısından motor ve duyu muayeneleri yapıldı. Cerrahinin süresi, toplam floroskopi süresi, medial pin için floroskopi süresi, Baumann açısı, humerokapitallar açı, son taşıma açısı ve eklem hareket açıklığı değerlendirildi. BULGULAR: Duyu incelemesinde Grup A’da üç kötü ve bir orta sonuç, Grup B’de iki kötü ve bir orta sonuç elde edildi. İstatististiksel olarak fark saptanmadı. Gruplar arasında cerrahi süre ve toplam floroskopi süresi açısından fark saptanmadı. Medial mini açık yapılan grupta medial pin fiksasyonu sırasında floroskopi süresi daha kısa saptandı. TARTIŞMA: Medial mini açık teknik ve perkütan tekniğin her ikisin dede iyatrojenik ulnar sinir yaralanma riski mevcuttur. Medial mini açık teknikte medial pin yerleştirme işlemi daha kısa süre floroskopi kullanımı açısından avantajlıdır. Anahtar sözcükler: Humerus; kırık; pediatrik; suprakondiler kırık; ulnar sinir. Ulus Travma Acil Cerrahi Derg 2016;22(4):350–354

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doi: 10.5505/tjtes.2015.20268

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ORIGIN A L A R T IC L E

Is the presence of linear fracture a predictor of delayed posterior fossa epidural hematoma? Atilla Kırcelli, M.D.,1 Ömer Özel, M.D.,2 Halil Can, M.D.,3 Ramazan Sarı, M.D.,4 Tufan Cansever, M.D.,1 İlhan Elmacı, M.D.5 1

Department of Neurosurgery, Başkent University Faculty of Medicine, İstanbul-Turkey

Department of Orthopaedic Surgery, Başkent University Faculty of Medicine, İstanbul-Turkey

Department of Neurosurgery, Private Medicine Hospital, İstanbul-Turkey

Department of Neurosurgery, Memorial Hizmet Hospital, İstanbul-Turkey

Department of Neurosurgery, Memorial Şişli Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Though traumatic posterior fossa epidural hematoma (PFEDH) is rare, the associated rates of morbidity and mortality are higher than those of supratentorial epidural hematoma (SEDH). Signs and symptoms may be silent and slow, but rapid deterioration may set in, resulting in death. With the more frequent use of computed tomography (CT), early diagnosis can be achieved in patients with cranial fractures who have suffered traumatic injury to the posterior fossa. However, some hematomas appear insignificant or are absent on initial tomography scans, and can only be detected by serial CT scans. These are called delayed epidural hematomas (EDHs). The association of EDHs in the supratentorial-infratentorial compartments with linear fracture and delayed EDH (DEDH) was presently investigated. METHODS: A total of 212 patients with SEDH and 22 with PFEDH diagnosed and treated in Göztepe Training and Research Hospital Neurosurgery Clinic between 1995 and 2005 were included. Of the PFEDH patients, 21 underwent surgery, and 1 was followed with conservative treatment. In this group, 4 patients underwent surgery for delayed posterior fossa epidural hematoma (DPFEDH). RESULTS: Mean age of patients with PFEDH was 12 years, and that of the patients with SEDH was 18 years. Classification made according to localization on cranial CT, in order of increasing frequency, revealed of EDHs that were parietal (27%), temporal (16%), and located in the posterior fossa regions (approximately 8%). Fracture line was detected on direct radiographs in 48% of SEDHs and 68% of PFEDHs. Incidence of DPFEDH in the infratentorial compartment was statistically significantly higher than incidence in the supratentorial compartment (p=0.007). Review of the entire EDH series revealed that the likelihood of DEDH development in the infratentorial compartment was 10.27 times higher in patients with linear fractures than in patients with supratentorial fractures (p<0.05). CONCLUSION: DPFEDH, combined with clinical deterioration, can be fatal. Accurate diagnosis and selection of surgery modality can be lifesaving. The high risk of EDH development in patients with a fracture line in the posterior fossa on direct radiographs should be kept in mind. These patients should be kept under close observation, and serial CT scans should be conducted when necessary. Key words: Delayed epidural hematoma; head trauma; posterior cranial fossa.

INTRODUCTION Traumatic posterior fossa epidural hematoma (PFEDH) is less common, compared to supratentorial epidural hemaAddress for correspondence: Atilla Kırcelli, M.D. Oymacı Sok, No: 7, Başkent Üniversitesi İstanbul Hastanesi, 34662 Altunizade, İstanbul, Turkey Tel: +90 216 - 554 15 00 E-mail: atillakircelli@gmail.com Qucik Response Code

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toma (SEDH). PFDEH accounts for 0.3% of all intracranial hematomas and 4–12% of all epidural hematomas (EDHs). [1–6] PFDEH usually develops secondary to trauma to the occipital, suboccipital, and retromastoid regions. Though clinical progression is slow, neurological progression is rapid and fatal in the absence of timely intervention. Diagnosis of PFEDH can be established by cranial computed tomography (CT) or magnetic resonance imaging.[7] Hematoma that induces mass effect should be surgically treated. Delayed posterior fossa epidural hematoma (DPFEDH) is extremely rare, but can occur following head injury. DPFEDH is defined as the absence of EDH with or without linear fracture on initial CT, followed by development or deterioration of clinical symptoms, or detection of EDH on serial CT scans. 355

Kırcelli et al. Is the presence of linear fracture a predictor of delayed posterior fossa epidural hematoma?

Presence of linear fracture is a demonstrated risk factor for delayed supratentorial epidural hematomas (DSEDHs). In the literature, DSEDH accounts for 9–10% of all EDHs. However, its potential as a risk factor for DPFEDH has yet to be addressed.[8–13] The present patient series included 234 patients with traumatic cranial EDH treated in Göztepe Training and Research Hospital Neurosurgery Clinic between 1995 and 2005, 22 of whom were diagnosed with PFEDH, and 212 of whom were diagnosed with SEDH. Patients were retrospectively compared and evaluated based on clinical and radiological findings. The present objective was to investigate whether linear fracture was a risk for DPFEDH development, and whether there was a difference in risk severity between linear fracture in the infratentorial and supratentorial compartments.

MATERIALS AND METHODS A total of 234 patients treated for traumatic cranial EDH between 1995 and 2005 were retrospectively analyzed based on clinical and radiological findings. From this series, findings of 22 patients with PFEDH (9.4%) and 212 (90.6%) with SEDH were retrospectively evaluated. Delayed EDH was detected in 4 of the 22 PFEDH patients and 2 of the 212 SEDH patients. Underlying causes were investigated. Direct radiographs were obtained in the lateral and anteroposterior planes in the 234 patients with head injury. Those with trauma to the occipital, suboccipital, or retromastoid regions were also examined with Towne’s radiography. In patients with fractures, fracture type and whether the fracture had crossed venous sinuses were noted. CT scan was performed in all patients, and recorded findings included enlargement of the trigone, temporal horn, and 3rd ventricle, 4th ventricle compression and shift, basal-ambient and quadrigeminal cistern compressions, and whether hematomas were bilateral. In addition, EDH volume was calculated using the equation: 0.5 height x depth x length. Upon admission, severity of head injury was classified according to the Glasgow Coma Scale (GCS) by Narayan,[14] as mild (GCS: 13–15), moderate (GCS: 9–12), or severe (GCS: 3–8). SEDH patients with a hematoma of less than 30 cm3 in volume, less than 15 mm in thickness, and with a midline shift of less than 5 mm were clinically observed and followed up, as were those with GCS greater than 8 but with no focal neurological deficit. In patients with PFEDH of greater than 5 mm in thickness on CT, and greater than 15 cm3 in volume, with mass effect resulting in fourth ventricle shift, ventricle compression and perimesencephalic cistern compression were surgically evacuated. Level of consciousness and severity of head injury on admission were considered during postoperative follow-up. Initial Glasgow Outcome Score (GOS) and examination results of 356

all patients were recorded. Of the patients diagnosed with PFEDH, 21 received surgical treatment, and 1 received conservative treatment. While type of surgery varied, depending on hematoma localization, paramedian or median suboccipital craniotomy was performed, as was evacuation of the EDH, followed by detection of the bleeding site and bleeding control, after which surgery was terminated. Of the 22 PFEDH patients, only 4 had DPFEDH, all of whom had linear fractures. Two SEDH patients developed DSEDH, none of whom had linear fractures.

Statistical Analysis Statistical analysis was performed using the GraphPad Prism program (version 3; GraphPad Software, Inc., San Diego, CA, USA). Mann-Whitney U-test was used to compare data with descriptive statistical methods (mean, SD), as well as with paired data. Fisher’s exact test and relative risk were used to compare qualitative data. A p value of p<0.05 was considered statistically significant.

RESULTS A total of 234 patients were analyzed retrospectively based on clinical and radiological features. Eight patients diagnosed with PFEDH (36%) were female, and 14 (64%) were male, with a ratio of 2:3. Fifty-one patients with SEDH were female (24%), and 161 (76%) were male, with a ratio of 1:3. Of the patients with EDH, 22 were diagnosed with PFEDH, and 212 with supratentorial EDH. Of the patients with PFEDH, 4 were diagnosed with DPFEDH (Fig. 1a–d). Of the patients with SEDH, 2 were diagnosed with DSEDH. Mean age of patients with PFEDH was 12 years, while that of patients with SEDH was 18 years. Incidence of supratentorial and infratentorial EDH in the 1st decade of life was significantly high (p<0.05), while incidence in the 2nd decade of life was quite considerably high: 56% and 82% in SEDH and PFEDH patients, respectively. Demographic characteristics are presented in Table 1. The most common causes of traumatic posterior fossa EDH include fall from a height, traffic accident, assault, and collision of the head with a solid object. Signs and symptoms of the 22 PFEDH patients were headache (17 patients), nausea and vomiting (15), impaired consciousness (14), and retromastoid, occipital, and suboccipital swelling (12). Though less common, symptoms including loss of consciousness, cerebellar dysfunction, diplopia, abducens paralysis, otorrhagia, neck stiffness, and anisocoria were encountered in otherwise asymptomatic patients (Table 2). Two of the 4 patients with DPFEDH presented with headache and nausea/vomiting, the other 2 with neurological disorientation. All were discharged in GOS 5 condition. Of the 212 patients with SEDH, 169 had swelling at the site Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

KÄąrcelli et al. Is the presence of linear fracture a predictor of delayed posterior fossa epidural hematoma?

Table 1. Demographic factors

Supratentorial Infratentorial EDH EDH

Gender Male

161

Female

Age (median)

Classification according to localization on cranial CT, in order of increasing frequency, revealed EDH in the temporal (16%), temporoparietal (22%), and parietal (27%) regions, while incidence of EDH in the posterior fossa was approximately 8% in the present series (Fig. 2). Overall incidence of DPFEDH was 2%. Regarding localization of PFEDH in the infratentorial compartment on CT scan, 5 EDHs showed bilateral and 17 unilateral localization. Two DPFEDHs showed bilateral and 2 showed unilateral localization. Mean PFEDH volume was 13.5 cm3 (range: 2.3â&#x20AC;&#x201C;45 cm3).

Trauma type

Fall from height

Traffic accident

Assaults & collisions

ED: Epidural hematomas.

Table 2. Comparison of cranial tomographic findings of posterior fossa epidural hematomas (PFEDHs) vs delayed posterior fossa epidural hematomas (DPFEDHs)

PFEDH DPFEDH

Temporal horn Normal

Enlargement

3 ventricle th

Normal

Enlargement

p 0.07

Normal

4 ventricle th

Normal

Compressed or shift

Basal cisterns Normal

Compressed

Ambient cisterns Normal

Compressed

Quadrigeminal cisterns Normal

Compressed

0.117

0.073

0.029**

0.09

Localization 0.21 Unilateral

Bilateral

of injury. The other most common symptoms included headache, nausea/vomiting, impaired consciousness, loss of conUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Fracture line was detected on direct radiography of 102 (48%) of the 212 SEDH patients, while direct radiographs of 110 (52%) patients showed normal findings. DSEDH was detected during follow-up of 2 patients with no fracture line on direct radiography (0.09%). Linear fracture was identified in 15 (68%) of the 22 PFEDH patients. Twelve patients had paramedian occipital fracture and 3 had occipital fracture crossing the transverse sinus at the midline. DPFEDH was noted in 4 patients (18%) whose direct radiographs revealed the presence of a fracture line.

0.259

Trigone 0.01** Enlargement

sciousness, lateralizing signs (hemiparesis, Babinski reflex), and herniation. Two patients had delayed SEDH in this group. There was no need to evacuate the hematoma, and a conservative approach was adopted. Both patients were discharged in GOS 5 condition.

No statistically significant difference was found in fracture distribution between patients with PFEDH and those with SDEH (p=0.11). However, occurrence of EDH was 2.14 times more likely in the infratentorial compartment than in the supratentorial compartment in patients with linear fracture (p>0.05). Incidence of DPFEDH was statistically significantly higher in the infratentorial compartment than in the supratentorial compartment (p=0.007). Probability of DPFEDH development in the presence or absence of fracture was 4.66 times higher in the infratentorial compartment than in the supratentorial compartment (p<0.05). Incidence of DPFEDH in the infratentorial compartment, in the presence of fracture, was statistically significantly higher than in the supratentorial compartment (p=0.0002). A review of the entire EDH series revealed that the probability of delayed EDH (DEDH) development in the infratentorial compartment in patients with linear fracture was 10.27 times higher than in patients with supratentorial fracture (p<0.05). PFEDHs and DPFEDHs were compared in terms of CT findings including ventricle compression and shift, and enlargement of the trigone, temporal horn, and third ventricle, indicating development of hydrocephalus. In cases of DPFEDH, enlargement of the trigone and compression of the ambient cistern, among basal cisterns, were significantly increased (p=0.01 and p=0.029, respectively) (Table 2). 357

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(a)

(b)

(c)

(d)

Figure 1. (a) Case 1: S.K., 9 years old, initial computed tomography (CT) view (above) and view after 24 hours (below). (b) Case 2: Ş.S., 13 years old, initial CT view (above) and view after 10 hours (below). (c) Case 3: S.Y.; 10 years old, initial CT view (above) and view after 12 hours (below). (d) Case 4: T.Ş., 33 years old, initial CT view (above) and view after 12 hours (below). 70 60 50 40 30 20 10 l to on Fr

rp io er st

rie

l ta

l ta rie

l ta on Fr

Pa Po

Te m

-p

Te m

Figure 2. Distribution of epidural hematomas (EDHs) according to localization on cranial CT.

DISCUSSION EDHs are defined as lesions that typically develop immediately after trauma and expand in volume in minutes. Following the alleviation of the tamponade effect on intracranial volume, EDHs constitute a threat to life.[15,16] These lesions may develop slowly and can be manageable, though prediction of the course of EDH is challenging. The posterior fossa is a rare location for EDH. In PFEDH, the deterioration of symptoms may be slow and silent. However, neurological progression is rapid and can be fatal if left untreated. Early diagnosis is crucial for survival. Diagnosis and cure of PFEDH was possible following the first case of successful surgery, reported by Coleman and Thompson in 1941. [17] However, until recently, diagnosis was challenging. As in the 358

first published case series, documented by Campbell, Fisher, Hooper, and Petit-Dutaillis et al., the difficulty in establishing diagnosis resulted in the deaths of almost half the patient population.[18–21] These authors emphasized that half of the population was in the pediatric age group and had occipital fractures crossing the sinus. Recently, the frequent use of CT has facilitated PFEDH diagnosis in patients with head injury, and the number of patients diagnosed with DEDH has increasingly grown. Some authors suggest that a CT scan should be performed in each patient with swelling in the occipital region or fracture of the occipital bone.[22,23] In the present series, CT scan was performed, after neurological progression, in 4 patients with linear fracture, and DPFEDH was noted in all. EDH is an accumulation of blood resulting from bleeding of extracerebral vessels, leading to an extra axial mass. Irreversible damage is difficult to prevent, due to epidural hemorrhage resulting in brain herniation and increased intracranial pressure. Today, the increasingly frequent use of CT in the differential diagnosis of patients with head injury has facilitated the diagnosis of EDH, resulting in a decreased mortality rate.[24] A control CT scan performed in the first 24 hours in patients kept under observation following head trauma can detect DPFEDH. Radiological changes precede clinical progression.[25] Though the mortality rate of DEDH has been reported as 5%, it was approximately 4.5% in the present series. The majority of the present PFEDH patients were in the second decade of life. Harwood and Nash reported that 30% of patients with linear fracture developed EDH, and that EDH can develop following trauma to the occipital region due to abundant diploic and dural vascularization in infants and chilUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Kırcelli et al. Is the presence of linear fracture a predictor of delayed posterior fossa epidural hematoma?

dren. Most of the present PFEDH patients (68%) were in the pediatric age group. Surgical intervention was not performed in 1 patient with PFEDH based on cranial CT findings, which showed a hematoma less than 5-mm thick, 10 cm3, and without mass effect. Of the patients who underwent surgery, those with bilateral EDH underwent median craniectomy, while those with unilateral EDH underwent suboccipital craniectomy on the side where the lesion was located. According to reports, incidence of bilateral PFEDH is approximately 30%, while it was approximately 23% in the present series.[8] In most cases, bleeding arises from the venous sinus, from posterior branches of the meningeal artery or diploic veins, and from the dural sinuses. The transverse or sigmoid sinus is usually responsible for acute bleeding.[26] A review of the literature revealed that prognosis of EDH is better in chronic and subacute cases. Prognosis is poor in acute cases, and perimesencephalic cistern-basal cistern compressions due to rapid mass effect caused by hematoma can be associated with mortality. In the present study, basal cistern compression was significantly higher in cases of DPFEDH, among all cases of PFEDH. Likewise, in spite of a significant increase in the width of the trigone, it is likely that mortality is associated with acute brain stem-pons compression and acute hydrocephalus due to ventricular occlusion. The presence of a linear fracture is a risk factor for EDH. Results of a case series comparing 77 patients with primary EDH and DEDH by Poon et al. showed that primary brain damage was associated with linear fracture, and that hemorrhage arising from torn dura mater or venous injury was more common, compared to meningeal artery injuries. The authors also made clear that DEDH-related symptoms including hyperventilation, osmotic diuretics, otorrhea, surgical decompression, hypovolemia, or hypotension were not included in their study. Several studies have reported incidence of DEDH in patients with minor head trauma and linear fracture to be approximately 1%.[27] In most series, incidence of DEDH in patients with or without fractures was approximately 9–10%. This number is likely to increase as CT becomes is more widely used. Poon et al. reported that incidence of DEDH in traumatic EDH was about 30%.[24] Adeloye and Onabanjo suggested that DEDH could be of venous origin, and that administration of hyperosmolar agents such as mannitol may result in the formation of DEDH through loss of the intracranial pressure-related tamponade effect on small dural venules. [9] A case report by Koulouris and Rizzoli demonstrated that contralateral EDH developed after alleviation of the tamponade effect of EDH following surgical decompression.[22] Goodkin and Zahniser,[16] in 1978, reported a case in which DEDH was documented by serial angiography. They suggested that DEDH could have been caused by increased blood pressure in a previously hypotensive and hypovolemic patient. A review of relevant studies showed that linear fracture line was present in 70% of PFEDH patients, and that most paUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

tients were in the pediatric age group. This finding supports the hypothesis that DEDH can be caused by a linear fracture, and is likely of diploic venous origin in this compartment.[4] In the present series, a linear fracture was present in 50% of EDH patients. In the present study, risk of PFEDH development in the presence of a linear fracture was 10.27 times higher than in patients with supratentorial fracture. Though the posterior cranial fossa is the largest of the 3 cranial fossae, the comparison of supratentorial and infratentorial compartments reveals differences in the development of EDH in the presence of a linear fracture. In the present study, probability of EDH development in patients with fracture was 2.14 times higher in the infratentorial compartment than in the supratentorial compartment, and 64% of patients with infratentorial EDH were in the pediatric age group. In addition, risk of DEDH development was 4.66 times higher in the infratentorial compartment, compared to the supratentorial compartment. In cases of head trauma, severity is correlated with the presence of linear fracture and primary brain damage. In a study by Roda et al.,[28] infratentorial and supratentorial lesions were found in 39.7% of patients with head-injuryrelated EDH. In the present series, PFEDH accompanied 45% of lesions. Outcome of traumatic EDH, an extracerebral lesion, is much better than those of other traumatic intracranial bleedings, when treated properly. Early diagnosis and surgery, if necessary, is the key point of treatment. Patients should be closely observed and followed up with CT, particularly those with head injury and linear fracture in the posterior fossa.

Conclusion DPFEDH, combined with clinical deterioration, can be fatal. Accurate diagnosis and choice of surgical modality can be lifesaving. However, the high risk of EDH in patients with a fracture line in the posterior fossa on direct radiography should be kept in mind. These patients should be kept under close observation and serial CT scans should be performed when necessary. Conflict of interest: None declared.

REFERENCES 1. Erşahin Y, Mutluer S, Güzelbag E. Extradural hematoma: analysis of 146 cases. Childs Nerv Syst 1993;9:96–9. 2. Ammirati M, Tomita T. Posterior fossa epidural hematoma during childhood. Neurosurgery 1984;14:541–4. 3. Duthie G, Reaper J, Tyagi A, Crimmins D, Chumas P. Extradural haematomas in children: a 10-year review. Br J Neurosurg 2009;23:596–600. 4. Bozbuğa M, Izgi N, Polat G, Gürel I. Posterior fossa epidural hematomas: observations on a series of 73 cases. Neurosurg Rev 1999;22:34–40. 5. Baykaner K, Alp H, Ceviker N, Keskil S, Seçkin Z. Observation of 95 patients with extradural hematoma and review of the literature. Surg Neurol 1988;30:339–41. 6. Jamieson KG, Yelland JD. Extradural hematoma. Report of 167 cases. J Neurosurg 1968;29:13–23. 7. d’Avella D, Cristofori L, Bricolo A, Tomasello F. Importance of mag-

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Kırcelli et al. Is the presence of linear fracture a predictor of delayed posterior fossa epidural hematoma? netic resonance imaging in the conservative management of posterior fossa epidural haematomas: case illustration. Acta Neurochir (Wien) 2000;142:717–8. 8. Abdul-Azeim SA, Binitie OP. Delayed traumatic epidural hematoma of the posterior fossa. Neurosciences (Riyadh) 2002;7:198–200. 9. Adeloye A, Onabanjo SO. Delayed post-traumatic extradural haemorrhage: a case report. East Afr Med J 1980;57:289–92. 10. Chandrasekaran S, Zainal J. Delayed traumatic extradural haematomas. Aust N Z J Surg 1993;63:780–3. 11. Domenicucci M, Signorini P, Strzelecki J, Delfini R. Delayed post-traumatic epidural hematoma. A review. Neurosurg Rev 1995;18:109–22. 12. Fankhauser H, Kiener M. Delayed development of extradural haematomas. Acta Neurochir (Wien) 1982;60:29,35. 13. Fankhauser H, Uske A, de Tribolet N. Delayed epidural hematoma. Apropos of a series of 8 cases. [Article in French] Neurochirurgie 1983;29:255–60. [Abstract] 14. Narayan RK, Greenberg RP, Miller JD, Enas GG, Choi SC, Kishore PR, et al. Improved confidence of outcome prediction in severe head injury. A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure. J Neurosurg 1981;54:751–62. 15. Gudeman SK, Kishore PR, Miller JD, Girevendulis AK, Lipper MH, Becker DP. The genesis and significance of delayed traumatic intracerebral hematoma. Neurosurgery 1979;5:309–13. 16. Goodkin R, Zahniser J. Sequential angiographic studies demonstrating delayed development of an acute epidural hematoma. Case report. J Neurosurg 1978;48:479–82. 17. Coleman CC, Thomson JL. Extradural hemorrhage in the posterior fossa. Surgery 1941;10:985–90.

18. Campbell E, Whıtfıeld RD, Greenwood R. Extradural hematomas of the posterior fossa. Ann Surg 1953;138:509–20. 19. Fisher RG, Kim JK, Sachs E Jr. Complication in posterior fossa due to occipital trauma; their operability. J Am Med Assoc 1958;167:176–82. 20. Hooper R. Observations on extradural haemorrhage. Br J Surg 1959;47:71–87. 21. Petit-Dutaillis D, Guiot G, Pertuıset B, Le Besneraıs Y. Extradural hematoma of posterior fossa; after a series of 6 cases. [Article in French] Neurochirurgie 1956;2:221–2. [Abstract] 22. Koulouris S, Rizzoli HV. Acute bilateral extradural hematoma: case report. Neurosurgery 1980;7:608–10. 23. Karasu A, Civelek E, Aras Y, Sabanci PA, Cansever T, Yanar H, et al. Analyses of clinical prognostic factors in operated traumatic acute subdural hematomas. Ulus Travma Acil Cerrahi Derg 2010;16:233–6. 24. Poon WS, Rehman SU, Poon CY, Li AK. Traumatic extradural hematoma of delayed onset is not a rarity. Neurosurgery 1992;30:681–6. 25. Roberson FC, Kishore PR, Miller JD, Lipper MH, Becker DP. The value of serial computerized tomography in the management of severe head injury. Surg Neurol 1979;12:161–7. 26. Kabataş S, Civelek E, Sencer A, Sencer S, Barlas O. A case of superior sagittal sinus thrombosis after closed head injury. Ulus Travma Acil Cerrahi Derg 2004;10:208–11. 27. Onal MB, Civelek E, Kırcelli A, Yakupoğlu H, Albayrak T. Re-formation of acute parietal epidural hematoma following rapid spontaneous resolution in a multitraumatic child: a case report. Ulus Travma Acil Cerrahi Derg 2012;18:524–6. 28. Roda JM, Giménez D, Pérez-Higueras A, Blázquez MG, Pérez-Alvarez M. Posterior fossa epidural hematomas: a review and synthesis. Surg Neurol 1983;19:419–24.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Lineer kırık varlığı, geç gelişen posterior fossa epidural hematomu açısından bir risk faktörümüdür? Dr. Atilla Kırcelli,1 Dr. Ömer Özel,2 Dr. Halil Can,3 Dr. Ramazan Sarı,4 Dr. Tufan Cansever,1 Dr. İlhan Elmacı5 Başkent Üniversitesi Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, İstanbul Başkent Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İstanbul Özel Medicine Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul 4 Memorial Hizmet Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul 5 Memorial Şişli Hastanesi, Beyin ve Sinir Cerrahisi Kiniği, İstanbul 1 2 3

AMAÇ: Travmatik posterior fossa epidural hematomları ender görülmelerine karşın mortalite ve morbiditesi suratentorial yerleşimli epidural hematomlardan daha yüksektir. Belirti ve bulguları silik ve belirsiz olmalarının yanında hızlı bir kötüleşme göstererek bilinç bozukluğundan komaya ve sonuçta ölüme yol açabilir. Bilgisayarlı tomografinin (BT) kullanımının posterior fossa travması geçirmiş kranium kırığı bulunan olgularda yaygınlaşması ile erken tanı konulabilmektedir. Ancak ilk çekilen tomografide görülmeyip seri çekimlerde yakalanan hematomlara geç gelişen epidural hematom’lar denmektedir. Çalışmamızda supratentorial-infratentorial kompartmanlarda gelişmiş epidural hematomların (EDH) lineer kırık varlığı ile ilişkisi ve geç dönemde gelişen epidural hematomlarla ilişkisi incelendi. GEREÇ VE YÖNTEM: Bu çalışmada 1995–2005 yıllarında kliniğimizde 212 supratentorial epidural hematom (SEDH) ve 22 posterior fossa epidural hematomu (PFEDH) tanısı ile tedavi edilen olgular sunuldu. PFEDH olgularından 21’i ameliyat edildi, 1 olgu konservatif takip edildi, bu grubun içinden 4 olgu ise gecikmiş posterior fossa epidural hematomu (GPFEDH) nedeniyle ameliyat edildi. BULGULAR: Posterior fossa epidural hematomu nedeniyle tedavi ettiğimiz hastaların yaş ortalamaları 12, SEDH nedeniyle tedavi ettiğimiz hastaların yaş ortalamaları 18 idi. Hematomlar, parietal bölgede %27, temporal bölgede %16 ve posterior fossada %8 oranlarında görülmekteydi. Supratentorial epidural hematom olan 212 hastanın %48’inde, PFEDH olgularının %68’inde lineer kırık mevcuttu. Posterior fossada geç gelişen eipdural hematom görülme sıklığı %2 idi. İnfratentorial kompartmanda geç gelişen epidural hematom görülme olasılığı ileri derecede supratentorial kompartmana nazaran anlamlıydı (p=0.007). Çalışmamızda lineer kırığı olupta posterior fossada EDH gelişme oranı 10.27 kat daha bulundu (p<0.05). TARTIŞMA: Geç gelişen posterior fossa epidural hematomları klinik detoryantasyonla beraber hastayı ölümcül sonuçlara götürebilmektedir. Gecikmiş posterior fossa epidural hematomlarının tanısı ve cerrahi modalite hayat kurtarıcı olmakla beraber posterior fossa direkt grafilerinde kırık hattı tespit edilen hastalarda yüksek oranda EDH gelişebileceği göz önünde bulundurulmalı, bu tarzda olan hastaları yakın gözlem altında tutmalı gerektiğinde seri BT çekimleri yapılmalıdır. Anahtar sözcükler: Geç gelişen epidural hematom; kafa travması; posterior kranial fossa. Ulus Travma Acil Cerrahi Derg 2016;22(4):355–360

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ORIGIN A L A R T IC L E

Implementation of the Ottawa ankle rules by general practitioners in the emergency department of a Turkish district hospital Murat Daş, M.D.,1 Aytun Temiz, M.D.,2 Yunsur Çevik, M.D.3 1

Department of Emergency Medicine, Balıkesir Edremit State Hospital, Balıkesir-Turkey

Department of Orthopaedics and Traumatology, Edremit State Hospital, Balıkesir-Turkey

Department of Emergency Medicine, Ankara Keçiören Training Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: The present objective was to assess implementation of the Ottawa ankle rules (OAR) as a method of fracture prediction in the emergency department (ED) of a Turkish state hospital. METHODS: Patients who presented to the ED of our hospital with acute ankle injury were evaluated. All were examined by a general practitioner, after which a series of ankle and foot x-rays (anteroposterior and lateral) were performed. Radiography was examined by a radiologist and an orthopedic surgeon, both of whom were blinded to OAR results. Radiographic results were compared to results of OAR implementation. Sensitivity and specificity of the OAR in the diagnosis of fracture was calculated. RESULTS: A total of 251 (61.97%) patients were diagnosed as positive (+) for fracture after OAR implementation, 154 (38.02%) as negative (–). Clinically significant fracture was detected in 62 (15.3%) patients. A total of 61 (98.4%) patients with significant fracture were OAR (+); 1 (1.6%) was OAR (–). However, 190 (55.4%) patients without fracture were OAR (+); 153 (44.6%) were OAR (–) (p<0.001). Sensitivity, specificity, and positive and negative predictive values of OAR implementation in the prediction of fracture were 98.39%, 44.61%, 24.30%, and 99.35%, respectively. Area under the curve (AUC) was 0.71. According to these results, it was determined that use of radiography could be reduced by 38.02% if the OAR were implemented. CONCLUSION: The OAR are a highly sensitive means of screening of patients with acute ankle and mid-foot injuries. Application of the OAR by well-trained general practitioners can lead to significant reduction in the number of x-rays performed, thereby reducing cost of treatment and radiation exposure, in addition to saving time for patients and staff. Keywords: General practitioners; Ottawa ankle rules.

INTRODUCTION Ankle and foot injuries are common clinical conditions, accounting for 6–12% of emergency department (ED) cases. [1,2] The majority of these patients undergo plain radiography to rule out fracture, while clinically significant fractures account for only 15% of the injuries.[3] This figure suggests that Address for correspondence: Aytun Temiz, M.D. Hasan Basri Çantay Mah., Tank Çiftliği Yolu Sokak, Altinkent Sitesi, E Blok, Daire 8, Balıkesir, Turkey Tel: +90 266 - 373 13 13 E-mail: aytuntemiz@hotmail.com Qucik Response Code

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a significant number of patients are unnecessarily subjected to x-ray exposure.[4] In an effort to reduce ED wait time and unnecessary radiography, Stiell et al.[5] from the University of Ottawa and the Ontario Ministry of Health developed a set of clinical guidelines known as the Ottawa ankle rules (OAR). The aim of OAR implementation is to exclude diagnosis of ankle and mid-foot fracture on the basis of a thorough physical examination. The OAR have been widely applied in many countries,[6–11] and are regarded as a highly sensitive and modestly specific method of detecting fracture in clinical setting.[12] However, the introduction of any new diagnostic method in a specific clinical setting and culture requires considerable caution, as sensitivity and specificity may be significantly affected.[1] In Turkey, a patient with musculoskeletal injury is typically first examined by a general practitioner at a local state hospital. For this reason, the present aim was to assess the efficacy of the OAR as a method of fracture prediction in the ED 361

Daş et al. Implementation of the Ottawa ankle rules by general practitioners in the emergency department of a Turkish district hospital

of a Turkish state hospital. It was hypothesized that the implementation of the OAR by general practitioners in an ED would significantly reduce the number of unnecessary x-rays, without increasing the number of missed fractures.

MATERIALS AND METHODS The present study was approved by the ethics committee of the Balikesir University Faculty of Medicine. It was a retrospective case-control analysis of prospectively planned and collected data. Consecutive patients who presented to the ED of our hospital with acute ankle injury between October 2014 and February 2015 were evaluated. Exclusion criteria were injuries that had occurred longer than 10 days prior, patient age younger than 18 years, those who were intoxicated or unconscious, as well as those with previously symptomatic ankle, insensate leg, open fractures, evidence of neurovascular compromise, or obvious ankle or foot deformities. All included patients were examined by a general practitioner in the ED. Examining practitioners attended a presentation regarding the use and implementation of the OAR, and received a printed card with a description (Fig. 1). In addition, descriptive posters of the OAR were hung in the ED. According to the OAR, clinically significant fracture should be suspected when bone tenderness is present along the distal 6 centimeters of the posterior, medial, or lateral malleolus, at the base of the 5th metatarsal and navicular bone, or when the patient is unable to bear weight, both in the immediate aftermath of the event and in the ED. Following OAR assessment, participants underwent a series of ankle and foot x-rays (anteroposterior and lateral). Radiography was interpreted by a radiologist and an orthopedic surgeon blinded to the OAR status of each patient. Any avulsed fracture fragment longer than 3 mm was considered clinically significant. If fracture fragment was shorter than 3 mm, the radiograph was interpreted as a clinically insignificant, and a result of “no fracture” was reported in analysis. Radiographic results were compared to the findings of OAR implementation in order to calculate OAR sensitivity and specificity in the diagnosis of fracture. Negative and positive predictive values, as well as area under the curve (AUC) were calculated. Statistical analysis was performed using SPSS software (version 22.0; SPSS Inc., Chicago, IL, USA). Patients with ankle sprain account for approximately 6% of all those presenting

to the ED,[1,2] a piece of information used for the present power analysis. With significance level of α=0.05 and margin of error of d=0.02, sample size was determined as n=405. Normalcy of distribution was checked using Shapiro-Wilk test. Descriptive statistics were expressed as median (minimum—maximum) for continuous variables with abnormal distribution, and as frequency, percentage for categorical variables. McNemar’s test was used to analyze categorical data of dependent variables.

RESULTS A total of 405 patients were presently included. Mean age was 37.46 (18–85) years, 248 (61.2%) patients were men, and 157 (38.8%) were women. The OAR positive (+) population included 251 (61.97%) patients, while the negative (–) population included 154 (38.02%) patients. Clinically significant fracture was detected in 62 (15.3%) patients. Lateral malleolus fracture was diagnosed in 23 (5.67%) patients, metatarsal fracture in 23 (5.67%), medial malleolus fracture in 4 (0.98%), navicular bone fracture in 4 (0.98%), first metatarsal fracture in 3 (0.74%), calcaneal fracture in 2 (0.49%), talus lateral process fracture in 2 (0.49%), and both medial and posterior malleolar fracture was diagnosed in 1 (0.24%) patient. No fracture was found in 343 (84.69%) patients. A total of 61 (98.4%) patients with significant fracture were OAR (+), and 1 (1.6%) was OAR (–). However, 190 (55.4%) patients without fracture were OAR (+), and 153 (44.6%) were OAR (–) (p<0.001; Fig. 2). Sensitivity, specificity, and positive and negative predictive values of OAR implementation in the prediction of fracture were 98.39%, 44.61%, 24.30%, and 99.35%, respectively (Table 1). AUC was 0.71. According to the present findings, a possible reduction in incidence of unnecessary radiography of 38.02% was determined. One case of first metatarsal fracture (1.6%) would have been missed if the decision to perform x-ray had been based solely on OAR result.

DISCUSSION The present results regarding implementation of the OAR in a Turkish ED were similar to those produced in other settings. Bachmann et al.[13] demonstrated that OAR sensitivity ranged from 96.4–99.6%, and specificity from 26.3–47.9%. Sensitivity represents the number of patients with the condition and

Table 1. Performance of the OAR in evaluation of ankle and foot injuries

Fracture (+) n (%)

Fracture (–) n (%)

Ottawa (+)

61 (98.4)

190 (55.4)

Positive predictive value 24.30%

Ottawa (–)

1 (1.6)

153 (44.6)

Negative predictive value 99.35%

Sensitivity 98.39%

Specificity 44.61%

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Daş et al. Implementation of the Ottawa ankle rules by general practitioners in the emergency department of a Turkish district hospital

Lateral view

Medial view Malleolar zone

A Posterior edge or tip of lateral malleolus - 6 cm

B Posterior edge or tip of [medial] malleolus - 6 cm

Mid-foot zone

C Base of fifth metatarsal A series of ankle x-ray films is required only if there is any pain in malleolar zone and any of these findings: • Bone tenderness at A • Bone tenderness at B • Inability to bear weight both immediately and in emergency department

D Navicular

A series of [foot] x-ray films is required only if there is any pain in mid-foot zone and any of these findings: • Bone tenderness at C • Bone tenderness at D • Inability to bear weight both immediately and in emergency department

Figure 1. Description of Ottawa ankle rules.

with a positive test.[14] For this reason, an OAR (–) finding is a reasonable indication that no fracture is present. Specificity represents the number of patients without the condition and with a negative test.[15] Specificity can be a useful indicator of the number of unnecessary events (eg. radiographs). Dwivedi et al.[4] reported 100% sensitivity and 36.76% specificity of OAR implementation, signifying that all clinically significant fractures were detected using OAR, and none were missed. Spanos et al.[16] reported 94.12% sensitivity and 37.65% specificity when OAR was implemented by a resident orthopedic surgeon. In a study conducted by Yavuz et al.,[17] patients were examined by an orthopedic surgeon or orthopedic resident in the ED, and sensitivity and specificity were reported as 94.7% and 69.6%, respectively. 100

Ottawa (+) Ottawa (–)

Fracture (+) (%)

Fracture (–) (%)

Figure 2. Comparison of patients with and without fracture, in terms of the OAR (p=0.001).

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Regarding OAR implementation by general physicians, Can et al.[18] reported 100% sensitivity and 17% specificity. In the present study, OAR was also implemented by general practitioners, and 98.39% sensitivity, 44.61% specificity was found. Though 1 case of non-displaced first metatarsal fracture was missed, we believe that OAR is a useful diagnostic tool for the detection of any clinically significant ankle or mid-foot fracture in the ED of a Turkish district hospital. A 30–40% reduction in the number of unnecessary radiographs following OAR implementation has been reported. It was presently determined that a reduction of 38.02% was possible, indicating that an approximate third of x-rays could be avoided with OAR application in the present ED setting. Reduction in xrays by even a third can cause significant impact on healthcare cost, in addition to the reduction in radiation hazards. Certain limitations may have affected the present study. Patients were recruited from the ED of a single hospital. In addition, while all examiners were trained in the application of the OAR, there are unavoidable differences among individuals in palpation technique and assessment of bone tenderness, which may have impacted the present results. Sample size was determined based on previously reported data, and may not have been sufficient for our general population. In conclusion, the OAR is a highly sensitive method of screening patients with acute ankle and mid-foot injuries. Application of the OAR by well-trained general practitioners may significantly reduce the number of x-rays performed, thereby reducing cost of treatment and radiation exposure, in addition to saving time for patients and hospital staff. It is well 363

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known that physical examination is very important in the detection of occult fracture. Patients with sharp bone tenderness and severe soft tissue swelling but negative radiographic results are considered to have a high likelihood of fracture, based on the OAR. We suggest that in these cases, ankles should be immobilized in casts to prevent potential fracture displacement.

emergency department. Acad Emerg Med 2007;14:955–9. 9. Pigman EC, Klug RK, Sanford S, Jolly BT. Evaluation of the Ottawa clinical decision rules for the use of radiography in acute ankle and midfoot injuries in the emergency department: an independent site assessment. Ann Emerg Med 1994;24:41–5. 10. Bessen T, Clark R, Shakib S, Hughes G. A multifaceted strategy for implementation of the Ottawa ankle rules in two emergency departments. BMJ 2009;339:b3056. 11. Leddy JJ, Kesari A, Smolinski RJ. Implementation of the Ottawa ankle rule in a university sports medicine center. Med Sci Sports Exerc 2002;34:57–62.

Conflict of interest: None declared.

REFERENCES 1. Knudsen R, Vijdea R, Damborg F. Validation of the Ottawa ankle rules in a Danish emergency department. Dan Med Bull 2010;57:A4142. 2. Wang X, Chang SM, Yu GR, Rao ZT. Clinical value of the Ottawa ankle rules for diagnosis of fractures in acute ankle injuries. PLoS One 2013;8:e63228. 3. Stiell IG, McKnight RD, Greenberg GH, McDowell I, Nair RC, Wells GA, et al. Implementation of the Ottawa ankle rules. JAMA 1994;271:827–32. 4. Dwivedi R, Ale SB. Evaluation of the accuracy of “Ottawa ankle rules” for predicting fractures in acute ankle and midfoot injuries. J Uni Collage Med Sci 2014;2:1–5. 5. Stiell IG, Greenberg GH, McKnight RD, Nair RC, McDowell I, Worthington JR. A study to develop clinical decision rules for the use of radiography in acute ankle injuries. Ann Emerg Med 1992;21:384–90. 6. Auleley GR, Ravaud P, Giraudeau B, Kerboull L, Nizard R, Massin P, et al. Implementation of the Ottawa ankle rules in France. A multicenter randomized controlled trial. JAMA 1997;277:1935–9. 7. Yuen MC, Sim SW, Lam HS, Tung WK. Validation of the Ottawa ankle rules in a Hong Kong ED. Am J Emerg Med 2001;19:429–32. 8. Stiell IG, Bennett C. Implementation of clinical decision rules in the

12. Stiell I, Wells G, Laupacis A, Brison R, Verbeek R, Vandemheen K, et al. Multicentre trial to introduce the Ottawa ankle rules for use of radiography in acute ankle injuries. Multicentre Ankle Rule Study Group. BMJ 1995;311:594–7. 13. Bachmann LM, Kolb E, Koller MT, Steurer J, ter Riet G. Accuracy of Ottawa ankle rules to exclude fractures of the ankle and mid-foot: systematic review. BMJ 2003;326:417. 14. Jenkin M, Sitler MR, Kelly JD. Clinical usefulness of the Ottawa Ankle Rules for detecting fractures of the ankle and midfoot. J Athl Train 2010;45:480–2. 15. Fritz JM, Wainner RS. Examining diagnostic tests: an evidence-based perspective. Phys Ther 2001;81:1546–64. 16. Spanos I, Samdanis V, Chytas A, Beslikas T, Hatzokos I. Implementation of the Ottawa ankle rules by resident orthopaedic surgeons in an emergency department. Clin Res Foot Ankle 2014;2:1000127. 17. Yavuz U, Sokucu S, Demir B, Yalcinkaya M, Cetinkaya E, Coskun M, et al. Evaluation of rutine radiographical necessity according to Ottawa rules in patients with ankle trauma. Goztepe Tip Dergisi 2013;28:204–8. 18. Can U, Ruckert R, Held U, Buchmann P, Platz A, Bachmann LM. Safety and efficiency of the Ottawa Ankle Rule in a Swiss population with ankle sprains. Swiss Med Wkly 2008;138:292–6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ottawa ayak bileği kurallarının ülkemizde devlet hastanesi acil servisinde görevli pratisyen hekimler tarafınca kullanımı Dr. Murat Daş,1 Dr. Aytun Temiz,2 Dr. Yunsur Çevik3 Balıkesir Edremit Devlet Hastanesi, Acil Tıp Kliniği, Balıkesir Edremit Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Balıkesir 3 Ankara Keçiören Eğitim Araştırma Hastanesi, Acil Tıp Kliniği, Ankara 1 2

AMAÇ: Ottawa ayak bileği kurallarının ülkemizde devlet hastanesinde görevli pratisyen hekimler tarafınca kullanılmasının etkinliğini araştırmak. GEREÇ VE YÖNTEM: İki yüz yataklı devlet hastanesi ikinci basamak acil servise, ayak-ayakbileği travması ile müracaat eden 405 hasta çalışmaya dahil edildi. Tüm hastalar pratisyen hekim tarafınca muayene edilerek Ottawa pozitif veya negatif olarak sınıflandırıldı. Tüm hastalara ön-arka ve yan, ayak ve ayak bileği grafisi çekildi. Grafiler, hastanın Ottawa grubunu bilmeyen ortopedi ve radyoloji uzmanlarınca değerlendirilerek klinik olarak anlamlı kırık olup olmadığı saptandı. Takiben sonuca göre Ottawa ayakbileği kuralı için duyarlılık, özgüllük, pozitif ve negatif kestirim değerleri hesaplandı. BULGULAR: İki yüz elli bir (%61.97) hasta Ottawa (+), 154 hasta (%38.02) Ottawa (–) olarak saptandı. Altmış iki (%15.3) hastada klinik olarak anlamlı kırık tespit edildi. Kırık olan 62 hastanın 61’inde (%98.4) Ottawa (+) idi. Deplase olmamış birinci metatars kırığı tespit edilen bir (%1.6) hastada Ottawa (–) idi. Bununla birlikte kırık saptanmayan 190 (%55.4) hasta Ottawa (+), 153 (%44.6) hasta Ottawa (–) idi (p<0.001). Duyarlılık, özgüllük, pozitif ve negatif kestirim değerleri sırasıyla %98.39, %44.61, %24.30 ve %99.35 idi. Eğri altında kalan alan 0.71 olarak hesaplandı. Bu sonuçlara göre Ottawa ayakbileği kurallarının olası radyolojik tetkik azaltma oranı %38.02 olarak tespit edildi. TARTIŞMA: Elde edilen sonuçlar literatür ile uyumludur. Ottawa ayak bileği kurallarının ülkemiz devlet hastanelerinin ikinci basamak acil servislerinde pratisyen hekimlerce kullanımının etkili ve güvenli olduğu kanaatindeyiz. Anahtar sözcükler: Ottawa ayak bileği kuralları; pratisyen hekim. Ulus Travma Acil Cerrahi Derg 2016;22(4):361–364

364

doi: 10.5505/tjtes.2016.72662

Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

ORİJİ N A L Ç A LI Ş M A

Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi Dr. İbrahim Üzün,1 Dr. Erdinç Özdemir,2 Dr. İpek Esen Melez,3 Dr. Deniz Oğuzhan Melez,4 Dr. Adem Akçakaya5 1

Adalet Bakanlığı Adli Tıp Kurumu, İstanbul; Akdeniz Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Antalya

Adalet Bakanlığı, Adli Tıp Kurumu Muş Adli Tıp Şube Müdürlüğü, Muş

Bezmialem Vakıf Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, İstanbul

Adalet Bakanlığı Adli Tıp Kurumu, İstanbul

Bezmialem Vakıf Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

ÖZET AMAÇ: Genel cerrahi, komplikasyon ile hata karşılaştırmasında karar vermenin zor olduğu dallardan biridir. Çalışmamızda tıbbi uygulamada hata iddiası bulunan genel cerrahi ölüm olgularında, tıbbi uygulama hatasının değerlendirilmesi için göz önüne alınan temel adli tıbbi parametrelerin sunulması ve bu kavramların literatür üzerinden tartışılması amaçlandı. GEREÇ VE YÖNTEM: 01.01.2012–31.12.2013 tarihleri arasında, genel cerrahi branşı hekimleri hakkında tıbbi uygulamada hata iddiası nedeniyle Adli Tıp Kurumu Birinci Adli Tıp İhtisas Kurulu’na gönderilmiş ve tıbbi uygulama ile ölümün illiyetli olduğu belirlenmiş olgular geriye dönük olarak incelendi. BULGULAR: Toplam 105 olgunun %21.9’unda (n=23) tıbbi uygulama hatası olduğu ve en sık primer hastalık tanılarının sırasıyla travma–yaralanma (n=32, %30.5), kolesistit (n=25, %23.8) ve apandisit (n=8, %7.6) olduğu görüldü. Tedavi şekilleri, tıbbi uygulamada hata kararı açısından karşılaştırıldığında, sadece medikal tedavi olan olgularda hata gözlenme oranı, cerrahi+medikal tedavi gören olgulara göre istatistiksel olarak anlamlı düzeyde yüksek bulundu (p=0.003; p<0.01). Ancak, acil ve elektif cerrahi tedaviler, tıbbi uygulamada hata kararı açısından karşılaştırıldığında istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05). Klinik tanı ile otopside belirlenen tanı arasındaki ilişkinin tıbbi uygulamada hata kararı üzerindeki etkisi değerlendirildiğinde; klinik tanı ve -otopsi var olduğunda- otopsi tanısının uyum durumu ile tıbbi uygulamada hata kararı arasında istatistiksel olarak anlamlı farklılık tespit edildi (p=0.031; p<0.05). Klinik tanının otopsi ile doğrulandığı olgularda, hata olduğu yönünde karar verilme oranı istatistiksel olarak anlamlı düzeyde düşük olarak bulundu (p=0.028; p<0.05). SONUÇ: Elde edilen sonuçlar yorumlandığında, Adli Tıp Kurumu’nun tıbbi uygulama hatası değerlendirmesinde otopsi verileri kadar klinik takip verilerini de dikkate aldığı, genel cerrahide medikal tedavinin doğru uygulanmasına önem verilmesi gerektiği ve hekimlerin acil şartlarda elektif şartlar kadar başarılı oldukları unsurları dikkat çekici bulunmuştur. Anahtar sözcükler: Adli tıp; genel cerrahi; otopsi; tıbbi uygulama hatası.

GİRİŞ Hatalı tıbbi uygulama, hastaya müdahale yetkisi bulunan tüm sağlık çalışanlarının standart tıbbi uygulamayı yapmaması, be-

Sorumlu yazar: Dr. Erdinç Özdemir, İstasyon Caddesi, Adalet Sarayı, Kat: 3, Adli Tıp, 49000 Muş. Tel: +90 436 - 212 36 58 E-posta: erdincoz.md@gmail.com Ulus Travma Acil Cerrahi Derg 2016;22(4):365–373 doi: 10.5505/tjtes.2015.26543 Telif hakkı 2016 TJTES

Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

ceri eksikliği veya hastaya tedavi vermemesi ile oluşan zarar olup bu durumda hastalık normal seyrinin dışına çıkar.[1,2] Tıbbi uygulamaların hemen hepsinde bir takım riskler vardır. Uygulamalar, riskler dikkate alınarak ve yarar zarar dengesi gözetilerek yapılır. Eğer tıbbi uygulama belirgin derecede hasta yararına ise, kesin olarak görülmesi beklenen veya görülme olasılığı bulunduğu bildirilen riskler uygulama için engel teşkil etmez. Hastanın bilgilendirilmesi dahilinde hekim bu zararların ortaya çıkmasından sorumlu tutulamaz. Bu kapsamda, hukukta yer alan ‘izin verilen risk’ kavramının tıbbi karşılığı komplikasyondur.[3,4] Bir başka tanımla, komplikasyon bir hastalığın seyri esnasında oluşan, mevcut hastalığa eklenen ikincil bir hastalık veya bozukluktur.[5] 365

Üzün ve ark. Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi

Genel cerrahi branşı, komplikasyon ile hata karşılaştırmasında iddiaların en fazla olduğu dallardan biridir.[6,7] Bu çalışmada, tıbbi uygulamada hata iddiası bulunan ölümlü genel cerrahi olgularında, branş hekiminin tıbbi uygulama hatasının olup olmadığı değerlendirilirken göz önüne alınan temel adli tıbbi parametrelerin sunulması ve literatür eşliğinde tartışılması amaçlandı.

GEREÇ VE YÖNTEM 01.01.2012–31.12.2013 tarihleri arasında Adli Tıp Kurumu Birinci Adli Tıp İhtisas Kurulu’na (ATK Birinci ATİK) gönderilmiş, genel cerrahi branşı hekimleri hakkında tıbbi uygulamada hata iddiası içeren ve tıbbi uygulama ile ölümün illiyetli olduğu belirlenmiş olgular geriye dönük olarak incelendi. Veriler kayıt altına alınırken; olgunun cinsiyeti, olay tarihindeki yaşı, olayın gerçekleştiği coğrafi bölge, müracaat edilen sağlık kuruluşu, iddiaya konu olan hekimin akademik ünvanı, tanıları, yapılan medikal ve/veya cerrahi tedaviler, komplikasyon varlığı ve türü, otopsi yapılma durumu, otopsinin tıbbi uygulamada hata kararındaki etkisi, tıbbi uygulama hatası meydana gelip gelmediği, tıbbi uygulama hatası tespit edilen olgularda hataların hangi süreçlerde meydana geldiği parametreleri incelendi. İstatistiksel analizler için NCSS (Number Cruncher Statistical System) 2007&PASS (Power Analysis and Sample Size) 2008 Statistical Software (Utah, USA) programı kullanıldı. Çalışma verileri değerlendirilirken tanımlayıcı istatistiksel metodların (ortalama, standart sapma, medyan, frekans, oran, minimum, maksimum) yanı sıra, niteliksel verilerin karşılaştırılmasında

Fisher’s Exact Test ve Yates Continuity Correction test (Yates düzeltmeli ki-kare) kullanıldı. Anlamlılık p<0.01 ve p<0.05 düzeylerinde değerlendirildi.

BULGULAR Çalışmamızda, belirlenmiş arama kriterlerini karşılayan 105 olgu tespit edildi. Olguların 23’ünde (%22) tıbbi uygulamada hata olduğu, 82’sinde (%78) ise olmadığı değerlendirildi. Olguların 67’sinin (%63.8) erkek, 38’inin (%36.2) kadın olduğu; en genç hastanın üç, en yaşlı hastanın 85 yaşında olduğu; ortalama yaşın ise 47.5±18.78 olduğu tespit edildi. Olguların gönderildiği coğrafi bölgeler değerlendirildiğinde, en fazla Marmara Bölgesi’nden geldiği (n=36, %34.2), hastanelerin dağılımına bakıldığında ise tedavilerin en sık devlet hastanesinde (n=48, %45.7) gerçekleştiği belirlendi. Tıbbi uygulamada hata varlığına göre olguların tedavi oldukları hastane türlerinin dağılımları arasında istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05) (Tablo 1). İncelenen bütün olgularda, kişinin takip ve tedavisini yapan, davaya konu olan ve hakkında tıbbi uygulamada hata iddiası bulunan hekimlerin ünvanları arasında, en sık uzman doktor (n=89, %84.8) ünvanı tespit edildi. Tıbbi uygulamada hata durumuna göre olguların tedavi oldukları hekimlerin ünvanlarının dağılımları arasında istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05) (Tablo 1). Tıbbi uygulamada hata iddiası olan olguların 34’ünün (%32.3) zorlamalı ölüm, 71’inin (%67.7) ise doğal ölüm olduğu tespit edildi. Zorlamalı ölüm olgularının dokuzunda (%26), doğal ölüm olgularının da 14’ünde (%19) tıbbi uygulamada hata kararının verildiği belirlendi. Tıbbi uygulamada hata durumu-

Tablo 1. Tıbbi uygulamada hata olgularının takip ve tedavilerinin yapıldığı sağlık kuruluşlarına göre ve tıbbi uygulama yapan sağlık personelinin akademik ünvanına göre dağılımı

Tıbbi uygulama hata durumu

Yok (n=82)

Test değeri

Var (n=23)

n % n %

Başvurulan hastane Devlet hastanesi

36 43.9 12 52.2 0.218 c0.641

E.A.H.*

14 17.1 5 21.7 0.264 d0.759

Özel hastane

24 29.3 4 17.4 0.759 c0.383 1 1.2 0 0.0 –

Özel poliklinik

d Üniversite hastanesi 7 8.5 2 8.7 0.001 1.000

–

Hekim ünvanı

Bilinmiyor‡

10 12.2 0 0.0 3.100 d0.113

Asistan doktor

1 1.2 0 0.0 –

Uzman doktor

68 82.9 21 91.3 0.976 0.513

Doçent doktor

d 2 2.4 1 4.3 0.236 0.528

Profesör doktor

d 1 1.2 1 4.3 0.941 0.392

– d

Eğitim ve Araştırma Hastanesi. Uzmanlık alanı belli olmayıp sadece ‘Dr.’ şeklinde ifade edilen kişi gösterilmiştir. c Yates Continuity Correction Test. d Fisher’s Exact Test. *

‡

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Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

Üzün ve ark. Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi

Tablo 2. Sonrasında ölüm gerçekleşen primer hastalık tanılarının dağılımı Tanı

n %

Travmalar – yaralanmalar

30.5

Kolesistit

25 23.8

Apandisit

8 7.6

Özefagus, mide ve bağırsak perforasyonları

6.7

Tümör – neoplazi

5.7

İleus

4 3.8

Tiroid hastalıkları

2.9

Özefagus, mide ve bağırsak kanamaları

2.9

Yanık

2 1.9

Hemoroid – anal kanal hastalıkları

Diğer‡

13 12.4

1.9

Toplam

105 100

*Bir olguda safra kesesi perforasyonu, kolesistiti başlığı altında değerlendirilmiştir. ‡ Divertikülit, varis, volvulus, dalak rüptürü, DIC, splenik arter rüptürü, akut pankreatit, aort anevrizma rüptürü, inguinal herni, batın TBC, gebelik, over perforasyonu, tuba rüptürü.

na göre zorlamalı – doğal ölüm olguları arasında istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05). Olguların hastalık tanıları incelendiğinde en sık ‘travmaya bağlı yaralanmalar’ şeklinde tanı aldıkları (n=32, %30.5) bunu kolesistit tanısının izlediği (n=25, %23.8) belirlendi (Tablo 2). Genel cerrahi branşı hakkında tıbbı uygulamada hata iddiası bulunan 105 olgunun 81’ine (%77.1) cerrahi+medikal, 24’üne (%22.9) sadece medikal işlem uygulanmış olup cerrahi işlem uygulanan 81 olgunun 44’üne (%54.3) acil cerrahi tedavi, 37’sine (%45.7) elektif cerrahi tedavi uygulandığı tespit edildi. Tıbbi uygulamada hata durumuna göre yapılan tedavi şekilleri arasında istatistiksel olarak ileri düzeyde anlamlı farklılık saptanmış olup sadece medikal tedavi olan olgularda hata gözlenme oranı, cerrahi+medikal tedavi gören olgulara göre anlamlı düzeyde yüksek bulundu (p=0.003; p<0.01) (Tablo 3). Olgularda komplikasyon varlığı değerlendirildiğinde; olguların

80’inde (%76.2) yapılan tedaviler sırasında komplikasyon geliştiği belirlendi. Meydana gelen komplikasyonlar arasında en sık enfeksiyon-sepsis (n=33, %41.3) grubunun, daha sonra organ yaralanmaları (n=13, %16.3) grubunun ve üçüncü olarak ise emboli-infarkt (n=8, %10) grubunun yer aldığı tespit edildi (Şekil 1). Komplikasyonların, olguların tıbbi uygulamada hata durumlarına göre dağılımları değerlendirildiğinde, hata olduğu yönünde karar verilen 23 olgunun 17’sinde (%73.9), olmadığı yönünde karar verilenlerin ise 63’ünde (%76.8) komplikasyon meydana geldiği tespit edildi. Tıbbi uygulamada hata durumuna göre olgularda komplikasyon gözlenme oranları arasında istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05). Tıbbi uygulamada hata kararı verilen 23 olguda hata nedenleri değerlendirildiğinde; olguların 11’inde (%47.8) tedavi sürecindeki eksikliklerden, sekizinde (%34.8) doğru tanı konulamamasından, üçünde (%13) takip sürecindeki eksikliklerden, birinde ise (%4.3) görevi ihmalden dolayı hata bulunduğu yönünde karara varıldığı tespit edildi. Tıbbi uygulamada hata iddiası bulunan olgulara otopsi yapılma durumları değerlendirildiğinde, feth-i kabir işlemi yapılan dört olguda otopsi yapılan gruba dahil edildiğinde, 105 olgunun 60’ına (%57.1) otopsi yapıldığı belirlendi. Otopsi yapılma durumunun, tıbbi uygulamada hata kararı verilmesindeki etkisi değerlendirildiğinde; tıbbi uygulamada hata olduğu yönünde karar verilen 23 olgunun 16’sında (%69.6), olmadığı yönünde karar verilen 82 olgunun 44’ünde (%53.7) otopsi yapılmış olup tıbbi uygulamada hata durumu ile otopsi oranları arasında istatistiksel olarak anlamlı ilişki saptanmadı (p>0.05). Klinik tanı ile otopside belirlenen tanı arasındaki ilişkinin tıbbi uygulamada hata kararı verilmesi üzerindeki etkisi değerlendirildiğinde; klinik tanı ve -otopsi var olduğunda- otopsi tanısının uyumlu olup olmaması ile tıbbi uygulamada hata yönünde karar verilip verilmemesi arasında istatistiksel olarak anlamlı farklılık tespit edildi (p=0.031; p<0.05). Otopsinin tıbbi uygulamada hata iddiası bulunan olgularda karar verilmesine katkısı değerlendirildiğinde; 105 olgunun sadece 60’ına otopsi yapılmış olduğu belirlendi. Olgular, otopsi tanısı ile klinik tanı arasındaki uyumu araştırmak amacı ile dört gruba (1. grup: Klinik tanı otopsi ile doğrulanmış, 2. grup: Klinik tanı otopsi

Tablo 3. Tıbbi uygulama hatasına göre uygulanan tedavilerin değerlendirilmesi

Tıbbi uygulama hata durumu

Yok (n=82)

Medikal

Var (n=23)

n % n %

Tedavi Cerrahi+madikal* 69 85.2 12 14.8

Test değeri

8.679

0.003‡

13 54.2 11 45.8

Endoskopi ve kolonoskopi gibi girişimsel işlemler cerrahi tedavi başlığı altında kabul edilmiştir. Yates Continuity Correction Test. ‡ p<0.01. *

Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

367

Üzün ve ark. Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi

Tablo 4. Tıbbi uygulama hatasına göre klinik tanı ile otopsi uyumluluğunun değerlendirilmesi ve ölüm sebebi belirlenmesinde kullanılan, klinik ve otopside tespit edilen tanıların uyumluluğu

Tıbbi uygulama hata durumu

Yok (n=82)

Test değeri

Var (n=23)

n % n %

Klinik – otopsi

Uyumsuz

22.7

56.3

tanı uyumu

Uyumlu

77.3

43.8

Grup 1

72.7

37.5

4.845

Grup 2

2.3

18.8

5.120

Grup 3

20.5

37.5

1.818

Grup 4

4.5

6.3

0.072

4.643

0.031*

0.028* 0.054 0.195 1.000

Yates Continuity Correction Test. Fisher’s Exact Test. * p<0.05. c

ile değişmiş, 3. grup: Klinik tanı yok, otopsi ile tanı konulmuş, 4. grup: Klinik tanı yok, otopsi ile tanı konulamamış) ayrıldığında; klinik tanı otopsi ile doğrulanmış olgular, tıbbi uygulamada hata değerlendirmesinde hata var kararı verilmiş olgular arasında %37.5; hata yok kararı verilmiş olgular arasında ise %72.7 oranında saptanmış olup; hata olduğu kararı verilme oranı istatistiksel olarak anlamlı düzeyde düşük olarak bulundu (p=0.028; p<0.05). Otopsi ile klinik tanı değişmişse, hata olduğu kararı verilme oranı yüksek bulundu, ancak olgu sayısının az olması nedeniyle istatistiksel olarak anlamlı bulunmadı (p>0,05). Klinik tanı yok iken otopsi ile tanı konulmuş olgular, tıbbi uygulamada hata değerlendirmesinde hata var kararı verilmiş olgular arasında %37.5; hata yok kararı verilmiş olgular arasında ise %20.5 oranında saptanmış olup aralarında istatistiksel olarak anlamlı farklılık görülmedi (p>0.05). Hem klinik hem otopsi tanısı olmayanlarda da hata oranları açısından anlamlı farklılık saptanmadı (p>0.05). ATK Birinci ATİK tarafından tıbbi uygulamada hata kararı verilen 23 olgu hakkındaki veriler detaylandırıldığında, olguların 3–80 yaş aralığında oldukları (ortalama: 45.26), erkek/kadın oranının 19/4, primer sağlık kuruluşunun en sık devlet hastanesi (n=12, %52.17), olayda suç isnat edilen hekimin akademik 35 30

25 20 15

O rg

4 *

iğ e

İle Ka us r ko diyo m va pl s ik kü as le y r Bi on rd en fa zl a

fe ks se iyo p n, ya sis ra la nm as Em ı bo li, M in ul fa tio rk rg t an ye t m Va e sk zl iğ ül i er ya ra la nm a

D S*

5 0

Şekil 1. Komplikasyon sıklıkları. *ARDS: Akut respiratuar distres sendromu. **Mide aspirasyonu, mezenter iskemi, bilateral vokal kord paralizisi.

368

ünvanının en sık uzman hekim (n=21, %91.30), primer hastalığın en sık travma – yaralanma ile ilgili (n=20, %86.96) olduğu görüldü. İlgili hekim tarafından tercih edilen tedavi türü açısından yapılan değerlendirmede cerrahi+medikal tedavi (n=12, %52.17) ile sadece medikal tedavinin (n=11, %47.83) yakın oranlarda olduğu ve en sık sepsis (n=6, %26.09) komplikasyonu ile karşılaşıldığı bulundu. Ayrıca, olguların dokuzunda (%39.13) klinik tanı ile otopsi tanısının uyumlu, yedisinde (%30.43) ise uyumsuz olduğu, en sık tıbbi uygulamada hata nedeninin tedavi hatası (n=11, %47.8) olduğu tespit edildi (Tablo 5).

TARTIŞMA Ülkemizde genel cerrahi branşı ile ilgili olarak tıbbi uygulamada hata iddiası olgularının sıklığının diğer tıp branşları ile karşılaştırılması yapıldığında genel cerrahi tıbbi uygulamada hata iddiası olgularının oranlarının %10.69–13.6 olup sıklık olarak genellikle üçüncü sırada olduğu belirtilmiştir.[6–8] Pakiş’in tıbbi uygulamada hata iddiası nedeni ile otopsisi yapılmış olguları değerlendiren tezinde, genel cerrahi branşı ile ilgili olguların %45.31’inde hata kararı verildiği belirtilmiştir.[9] Genel cerrahi branş hekimlerinin tıbbi uygulamalarını kapsayan, tıbbi müdahale ile ölüm arasında illiyet bağı kurulmuş olan ve yine aynı hekim veya hekimlerin tıbbi uygulamada hatalarının bulunduğu iddiasıyla sanık durumunda oldukları olguları kapsayan bu çalışmamızda, hata kararı oranı %21.90 olarak tespit edilmiştir. Adli Tıp Kurumu’nun tıbbi uygulama hataları konusunda kendi istatistikleri açısından yapılan çalışmalarda, bu oranın nörolojinöroşirürji alanlarında %31.9 ve üroloji alanında %30 olduğu, acil sınıfına giren tüm olgular şeklinde sınıflandığında %38, yardımcı sağlık personeli hataları şeklinde sınıflandığında %22.5 olarak bulunduğu, diş hekimliği alanında ise %39 oranında olduğu görülmektedir.[10–14] Sağlık kuruluşları arasında tıbbi uygulamada hata iddiasına neden olan olayın İrez’in tez çalışmasında %83.3’lük, Özkaya’nın Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

E.A.H.

Erkek

Kadın

Erkek

D.H.

E.A.H.

D.H.

Ü.H.

E.A.H.

Uz. Dr.

Prof. Dr.

Uz. Dr.

Volvulus

Özefagus perforasyonu

Taşlı kolesistit

Yanık

Jejunum, kolon perforasyonu

Medikal

Cerrahi+medikal

Medikal

Cerrahi+medikal

Medikal

Cerrahi+medikal

Yok

Sepsis

Duodenum perforasyonu

Multiorgan yetmezliği

Peritonit, sepsis

Yok

Peritonit, sepsis

Nekrotizan fasiit

Otopsi yok

Klinik – otopsi tanı uyumu

Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

Erkek

Kadın

D.H.

Ö.H.

Uz. Dr.

Mide perforasyonu

İleus

Hemoroid, anal fissür

Taşlı kolesistit

Medikal

Cerrahi+medikal

Sepsis

Multiorgan yetmezliği

Nekrotizan fasiit

Kardiyovasküler koplikasyon

Otopsi yok

Kadın

Erkek

D.H.

Uz. Dr.

Uz. Dr. Taşlı kolesistit

Aort anevrizma rüptürü

Medikal Cerrahi+medikal

Yok Duodenum perforasyonu

Erkek

Ö.H.

Ü.H.

Uz. Dr.

Doç. Dr. Taşlı kolesistit

Mezenter rüptürü

Mide perforasyonu, ince bağırsak

Cerrahi+medikal

Erkek

Ö.H.

D.H.

E.A.H.

Uz. Dr.

Taşlı kolesistit

Jejunum perforasyonu

Taşlı kolesistit

Mezenter rüptürü

Diyafragma, kolon perforasyonu

Cerrahi+medikal

Medikal

Cerrahi+medikal

Medikal

Cerrahi+medikal

Mide perforasyonu

Peritonit, sepsis

Karaciğer yaralanması, gossipiboma

Yok

Sepsis

Otopsi yok

Erkek

D.H.

Uz. Dr.

Taşlı kolesistit karotis arter yaralanması

Pnömotoraks, juguler ven,

Medikal

Cerrahi+medikal

Yok

İnce bağırsak perforasyonu

Eksik ve özensiz muayene

Eksik eylem/tedaviyi tamamlamamak

yönetememek

Tedavi takibinde eksiklik/komplikasyonu

Eksik ve özensiz muayene

Yöntem doğru işlem kusurlu

Eksik ve özensiz muayene

Yanlış tanı koymak

Yöntem doğru işlem kusurlu

Eksik eylem/tedaviyi tamamlamamak

yönetememek

Tedavi takibinde eksiklik/komplikasyonu

Eksik eylem/tedaviyi tamamlamamak

yaptırmamak

Gerekli tetkik ve grafileri istememek/

Görev ihmali

Eksik eylem/tedaviyi tamamlamamak

Yöntem doğru işlem kusurlu

yönetememek

Tedavi takibinde eksiklik/komplikasyonu

Eksik eylem/tedaviyi tamamlamamak

Yöntem doğru işlem kusurlu

Yanlış tanı koymak

Eksik eylem/tedaviyi tamamlamamak

Eksik ve özensiz muayene

Tıbbi uygulama hatası nedeni

D.H.: Devlet hastanesi; E.A.H.: Eğitim ve araştırma hastanesi; Ü.H.: Üniversite hastanesi; Ö.H.: Özel hastane; 1: Klinik tanı otopsi ile doğrulanmış; 2: Klinik tanı otopsi ile değişmiş; 3: Klinik tanı yok otopsi ile tanı konmuş; 4: Klinik ve otopsi tanı yok.

ve kalın bağırsak yaralanması

Yok

Medikal

over yaralanması

Uz. Dr. İnce bağırsak, rektum perforasyonu,

Kadın

Akut apendisit

Cerrahi+medikal

E.A.H.

Pnömotoraks, ileum perforasyonu

Erkek

Uz. Dr.

D.H.

Erkek

Hekim Primer hastalık tanısı Tedavi Komplikasyon unvanı

Olgu Yaş Cinsiyet Hastane

Tablo 5. ATK Birinci ATİK tarafından tıbbi uygulama hatası kararı verilen olgular

Üzün ve ark. Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi

369

Üzün ve ark. Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi

tez çalışmasında %39.7’lik, Gündoğmuş ve ark. çalışmasında %39.6’lık, Büken ve ark. çalışmasında ise %40.1’lik oranla devlet hastanelerinde meydana geldiği belirtilmiştir.[6,14–16] Nabil ve ark. Yemen’de yaptıkları bir çalışmada tıbbi uygulamada hata olgularının %51 ve Samarkandi’nin Suudi Arabistan’da yaptığı 1537 olgudan oluşan çalışmada %46.2 (n=710) oranları ile en sık devlet hastanesinde meydana geldiği belirtilmiştir.[17,18] Bizim çalışmamızda da, tıbbi uygulama hatasına konu oluşturan müdahalenin gerçekleştiği hastanenin ilk sırada devlet hastaneleri (%45.7) olduğu tespit edilmiştir. Ancak tıbbi uygulamada hata durumuna göre olguların başvurdukları hastanelerin dağılımları arasında istatistiksel olarak anlamlı farklılık saptanmamıştır (p>0.05). Sağlık Bakanlığı’nın 2013 verilerine göre Sağlık Bakanlığı bünyesine dâhil hastanelere (devlet hastanesi ile eğitim ve araştırma hastaneleri) müracaat sayısı 277.485.135 iken bu sayının üniversite hastanelerine 29.985.697, özel hastanelere ise 71.341.411 olduğu ve kişi başı hastanelere müracaat sayısının 4.9 olduğu belirtilmiştir.[19] Buna göre, ‘sadece devlet hastanelerine müracaat sayısı’ hakkında net bir bilgi elde edilememiş olmasına rağmen Sağlık Bakanlığı’na bağlı hastanelere müracaat sayısının diğer hastanelerden belirgin şekilde fazla olması bize en çok müracaatın yine de devlet hastanelerine yapılmış olduğunu düşündürmüştür. Ancak net bir sayı olmadığı için düzeltilmiş bir oran hesabı yapılarak ileri bir yoruma gidilememiştir. Yeterli ve yetkili uzmanlar, daha komplike ve daha ağır operasyonlara müdahale ettiklerinden, dava edilme ve daha yüksek tazminat istemiyle karşılaşma ihtimalleri fazladır.[12,20,21] Çalışmamızda hem tıbbi uygulamada hata suçlaması açısından, hem de hatalı bulunma açısından ilk sırayı uzman hekimlerin (n=89, %84.8) aldığı tespit edilmiştir. Ancak hekimin akademik derecesi ile hata durumu arasında istatistiksel olarak anlamlı farklılık saptanmamıştır (p>0.05). Literatürde bu yönde istatistiksel anlamlılık değerlendirmesi yapılmamış olmakla birlikte, yeterli ve yetkili uzmanların dava edilme ve daha yüksek tazminat istemiyle karşılaşma ihtimalleri kavramı ile çalışmamızdan elde edilen bu veri uyumlu olarak değerlendirilmiştir. Travma olguları tıbbi uygulamada hata açısından yüksek riskli bir alan olarak kabul edilir.[22] Travmaya uğramış genel cerrahi olgularında dava riski az olmasına rağmen yüksek tazminat ödemeleri yönünde eğilim olduğu belirtilmiştir.[23] Yaycı ve ark. çalışmasında travmaya uğramış genel cerrahi olgularının %31.8’inde, travma dışı genel cerrahi olgularının ise %62.5’inde tıbbi uygulamada hata olduğu belirtilmiştir.[24] Bunun yanında Erkol ve ark. tıbbi uygulamada hata durumu yönünde görüş istenen doğal nedenlerle troidektomi yapılmış olguları kapsayan çalışmasında da, olguların sadece üçünde (%10.7) ölüm meydana geldiği, bu ölümlü olguların ikisinde de (%66.7) tıbbi uygulamada hata olduğu bildirilmiştir.[25] Bizim çalışmamızda tıbbi uygulamada hata iddiası olan olguların %32.3’ünün (n=34) zorlamalı ölüm (genel beden travması, kesici alet yaralanması, ateşli silah yaralanması, yanıklar), %67.7’sinin (n=71) doğal ölüm sınıfında olduğu görülmüştür. Zorlamalı ölüm olgularının %26’sında (n=9), doğal ölüm olgularının ise %19’unda (n=14) 370

tıbbi uygulamada hata olduğu yönünde karar verildiği tespit edilmiştir. Ancak ölüm türü (zorlamalı ölüm–doğal ölüm) ile hata durumu arasında istatistiksel olarak anlamlı farklılık saptanmamıştır (p>0.05). Bunun, serimizdeki genel cerrahi kapsamında yer alan doğal ölüm olgularının sayısının da fazla olmasından kaynaklandığı düşünülmüştür. Genel cerrahi polikliniğine başvuran ya da genel cerrahi tarafından konsülte edilen olgularda fizik muayene bulguları ve yaklaşıma göre gerekli tetkik ve görüntüleme yöntemleri sonucunda herhangi bir karın içi patolojik bulgu ve belirtisi olanlara laparotomik veya laparoskopik cerrahi tedavi, geri kalan hastalara ise bir süre klinik takip altında medikal tedavi uygulanabileceği bildirilmiştir. Fizik muayene bulguları ile inceleme ve medikal tedavi sonrası kesin cerrahi müdahale endikasyonu konamayan, ancak medikal tedavinin de riskli olabileceği düşünülen olgularda diyagnostik laparoskopinin yararlı olacağı belirtilmiştir.[26] Rutin uygulanan acil laparotomilerin, %40’lara varan oranda negatif laparotomi ile sonuçlanabileceği, bu hastaların %5–22’sinde ciddi morbidite, %0.5’inde ise mortalite gelişebileceği de belirtilmiştir.[27–29] Leape ve ark. çalışmasında cerrahların ihmalkâr davranışları sonucu istenmeyen sonuçların meydana gelmesinin, cerrahi tedavi uygulanmayan hastalarda cerrahi tedavi uygulananlara göre daha fazla olduğu bildirilmiştir.[30] Çalışmamızda olguların %77.1’ine (n=81) cerrahi ile birlikte medikal tedavi uygulandığı, %22.9’una (n=24) ise sadece medikal tedavi uygulandığı görülmüştür. Cerrahi+medikal tedavi yapılan olguların %14.8’inde (n=12), sadece medikal tedavi yapılan olguların ise %45.8’inde (n=11) tıbbi uygulamada hata olduğu tespit edilmiştir. Buna göre, tercih edilen tedavi şekli (medikal+cerrahi – sadece medikal) ile hata durumu arasında istatistiksel düzeyde anlamlı farklılıklar saptanmıştır (p=0.003; p<0.01). Sadece medikal tedavi uygulanan olgularda tıbbi uygulama hata oranı, medikal+cerrahi tedavinin birlikte tercih edildiği olgulardaki hata oranına göre anlamlı düzeyde yüksek bulunmuştur. Bu veriler, Leape ve ark. çalışması ile uyumlu olarak değerlendirilmiş ancak sadece medikal tedavi uygulanan grupta oluşan olumsuz sonuçların, uygulanması gereken bir cerrahi işlem atlandığından mı yoksa yapılması gereken medikal tedavide doğru bir uygulama sağlanamadığından mı meydana geldiğine dair devam çalışmalarının yapılabileceği düşünülmüştür. Stewart ve ark. çalışmasında acil cerrahi uygulanan hastaların tıbbi uygulamada hata yönündeki şikâyetlerinin az olduğu, bunun acil cerrahi uygulanan hasta beklentisinin elektif cerrahi hastalarına göre daha az olduğundan kaynaklandığının düşünüldüğü belirtilmiştir.[23] Çalışmamızda olguların %41.9’unda (n=44) acil cerrahi, %35.2’sinde (n=37) elektif cerrahi uygulandığı belirlenmiştir. Acil cerrahi tedavi uygulananların %11.4’ünde (n=5), elektif cerrahi uygulananların ise %18.9’unda (n=7) tıbbi uygulamada hata olduğu tespit edilmiştir. Ancak cerrahi tedavinin acil veya elektif olması ile tıbbi uygulamada hata durumu arasında istatistiksel olarak anlamlı farklılık saptanmamıştır (p>0.05). Acil durumlarda zaman baskısı altında daha fazla hata yapılması beklenirken böyle tesUlus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

Üzün ve ark. Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi

pit edilmemiş olması, genel cerrahların acil durum karşısında, elektif koşullardaki kadar dikkatli davranabildiklerini gösterir niteliktedir. Bunun yanında adli tıbbi değerlendirmede, tıbbi uygulamada hata durumu yönünden görüş bildirilirken, acil cerrahi girişimlerde komplikasyon olasılığının ve komplikasyon takibinin daha zor olduğunun göz önüne alındığı düşünülebilir.

uygulamada hata durumu arasında yapılan istatistiksel analizde de anlamlı farklılık saptanmamıştır (p>0.05). Tüm bunlar birlikte değerlendirildiğinde, genel cerrahi ile ilişkili olarak ölümle sonuçlanan olgularda, ölüme neden olan komplikasyonların genel cerrahi hekimleri tarafından uygun şekilde yönetildikleri düşünülmüştür.

Komplikasyon, hukukta “izin verilen risk” kavramının tıbbi karşılığı olup[3,4] bir hastalığı seyri esnasında (perimedikal – postmedikal) oluşan, mevcut hastalığa eklenen ikincil bir hastalık veya bozukluk olarak tanımlanır.[5] Komplikasyonlar, tıbbi bakım maliyetlerinde büyük yük meydana getiren, morbidite ve mortaliteye sebep olan önlenebilir durumlardır. Bu nedenle komplikasyon, hasta, hekim ve ilgili sağlık kuruluşu tarafında istenmeyen bir sonuçtur. Bu istenmeyen sonuç, tıp bilimi tarafından belirlenmiş sınırlarda “olabilir” şeklinde kabul görmektedir. Amerika Birleşik Devletleri’nde Sağlık ve İnsani Hizmetler Bakanlığı’nın 2014 yılında çıkan raporunda, komplikasyon oranı 1990 yılında %9.3 iken, bu oranın 2012 yılında %83.6 olduğu belirtilmiştir.[31] Muhtemelen, gelişen tanı yöntemleri ve hastaların hastalıkları hakkındaki bilinç düzeyi artışı sonucu, hekimlerin komplikasyon tanısı koyabilme başarıları artmaktadır, ancak komplikasyonların doğru tanı, takip ve tedavisi sağlandığında bu süreç tıbbi uygulamada hata olarak kabul edilmediğinden, komplikasyon oranlarındaki artış oranlarının tümü tıbbi uygulamada hata oranlarına artış olarak yansımamaktadır. Ancak bunun için komplikasyon yönetiminde eksik ve özensiz yaklaşımın olmaması gerekir. Komplikasyon yönetiminin, ilgili hekimin hasta ile ilk temasından itibaren başlayıp hastanın salah ile taburcu edilmesinden sonra devam eden, hastanın tedavi görmesine neden olan durum ile ilişkili rutin sağlık taramalarını da kapsayan süreç boyunca yapılması beklenir. Bu kavram içinde ilk hedef komplikasyonun meydana gelmemesi için gerekli tedbirlerin alınmasıdır. Sonrasında ameliyat sonrası gelişebilecek komplikasyonların tespitine dair gerekli ve yeterli kontrollerin yapılması, gelişmiş ise zamanında tanısının konulup uygun tedavi yönteminin seçilmesi ve takibinin sürdürülmesi komplikasyon yönetiminin uygun yapılma kriterleridir. Eğer bu kriterlere göre komplikasyon yönetiminde bir eksiklik tespit edilmemiş ise, istenmeyen sonuç olarak meydana gelmiş olan komplikasyondan dolayı ilgili sağlık personeline hata verilmez.[32] Literatürdeki cerrahi operasyonlar ile ilgili çalışmalar değerlendirildiğinde; Dindo ve ark. çalışmasında %16.4 oranında komplikasyon tespit edilmiş olduğu, en sık komplikasyon türünün minör risk oluşturan komplikasyonlar olduğu, Wanzel ve ark. çalışmasında da %39 oranında komplikasyon tespit edilmiş olduğu, en sık komplikasyon türünün respiratuvar komplikasyonlar olduğu belirtilmiştir. [33,34] Çalışmamızda olguların tümünde ölüm gerçekleşmiş olup komplikasyon gelişme oranı %76.2 (n=80) olarak tespit edilmiştir. En sık tespit edilen komplikasyonun enfeksiyon – sepsis olduğu belirlenmiştir. Çalışmamızda literatürle karşılaştırıldığında yüksek olarak tespit edilen komplikasyon oranının ve en sık tespit edilen komplikasyonun sepsis olmasının, çalışmamızın ölümlü olgular üzerinden yapılmış olmasından kaynaklandığı düşünülmüştür. Komplikasyon gözlenme oranları ile tıbbi

Hasta ve hekim açısından adaletin doğru bir çizgide gerçekleşebilmesi için, ölümle sonuçlanan, tıbbi uygulamada hata iddiası bulunan olgularda, otopsinin gerekliliği birçok araştırmacı tarafından vurgulanmaktadır.[35–38] Ülkemizdeki otopsinin tıbbi uygulamada hata iddiası bulunan olgulardaki önemine dair Pakiş ve Algan’ın yapmış olduğu tez çalışmalarında, ortak sonuç olarak otopside başlıca tanı değişikliği saptanan grupta, saptanmayan gruba göre anlamlı derecede yüksek olarak tıbbi uygulamada hata varlığı yönünde karar verildiği belirtilmiştir.[7,9] Çalışmamızda otopsi yapılıp yapılmama ile tıbbi uygulama hata durumu arasında yapılan istatistiksel analizde anlamlı ilişki saptanmamıştır (p>0.05). Bunun yanında klinik tanı ve -otopsi var olduğunda- otopsi tanısının uyumlu olup olmaması ile tıbbi uygulamada hata yönünde karar verilip verilmemesi arasında anlamlı bir fark olup olmadığını göstermek amacıyla yapılan istatistiksel analizde anlamlı farklılık tespit edilmiştir (p=0.031; p<0.05). Klinik tanı ile otopsi arasında uyum gözlenmeyen olgularda hata verilme oranı, klinik tanı ile otopsi arasında uyum gözlenen olgulara göre anlamlı düzeyde yüksek bulunmuştur. Klinik tanı otopsi ile doğrulanmış olgularda hatalı bulma oranı istatistiksel olarak anlamlı düzeyde düşük olarak bulunmuştur (p=0.028; p<0.05). Otopsi ile klinik tanı değişmişse, hata saptanma oranı yüksek bulunmuş, ancak olgu sayısı nedeniyle istatistiksel olarak anlamlı bulunmamıştır (p>0.05). Klinikte tanı konulamayıp otopside tanı konulmuş olgularda tıbbi uygulamada hata olup olmaması açısından aralarında anlamlı bir farklılık tespit edilmemiştir (p>0.05). Klinik ve otopsi tanısı olmayanlarda da hata oranları açısından anlamlı farklılık saptanmamıştır (p>0.05) (Tablo 4). Tüm bunlar birlikte değerlendirildiğinde; çalışmamızda, otopsi tanısı ve klinik tanı uyumluluğu ile tıbbi uygulamada hata kararı verilip verilmemesi arasındaki ilişki incelendiğinde elde edilen sonuçlar, ATK Birinci ATİK kararlarında klinik verilerin otopsi verilerden daha güçlü bir etkisinin bulunduğunu düşündürmektedir. Çünkü klinik tanıyı destekleyen otopsi tanısı mevcut olduğunda, hata vermeme yönünde daha rahat bir şekilde karar verilmiş olduğu, ancak klinik tanı otopsi tanısı tarafından çürütüldüğünde veya klinik tanı konulamamış olduğunda otopsi tanısı varken tıbbi uygulama hatası verme oranlarında aynı istatistik anlamlılığa ulaşacak bir karar verme rahatlığı bulunmadığı dikkati çekmektedir. Ancak yine de, özellikle klinik tanının otopsi tanısı ile çürütüldüğü durumun bulunduğu dosya sayısı az olduğundan ve tüm dosyalarda da tıbbi uygulamada hata türü tanı koyabilme ile ilişkili olmadığından, anlamlılık düzeyinin istatistiksel olarak yakalanamamış olması beklenebilir bir sonuçtur. Benzer şekilde, klinik tanı yok iken otopsi ile tanı konulmuş olgular da zaten klinik olarak tanı konulması zor olan tablolar olarak değerlendirilerek -volvulus, aort anevrizma rüptürü, özefagus-mide-bağırsak perforasyonu, cerrahi işlem sırasında ani

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Üzün ve ark. Ölümle sonuçlanan acil ve elektif genel cerrahi olgularında tıbbi uygulama hatasının değerlendirilmesi

kardiyak ölüm;[9,39–41] bir başka deyişle klinik verilerin otopsi verilerinden daha ön planda tutulması nedeni ile değil, dosya incelenmesinde tablonun klinikte tanısının güç olduğu değerlendirildiğinden hata verilememe eğilimi görülmüş olabilir. Bu nedenle, bu çalışmanın arkasından yapılması planlanabilecek devam çalışmalarında başka zaman dilimlerine ait ve bu özellikleri gösteren daha fazla sayıda dosya elde edilirse, bu parametrelerin karşılaştırılması ile ATK Birinci ATİK’nin karar verme eğilimlerinin daha net ortaya konulabileceği düşünülmüştür. Benzer şekilde, çalışmamızda, klinik ve otopside tanı konulamamış olarak tespit edilen üç olgu için de, genelleme ile yorum yapmak yanlış değerlendirmelere açık olacağından bir olguda hata verilmiş olması iki olguda verilmemiş olmasının yine tanı koymanın güç olduğu kendine has klinik durumlar nedeniyle gerçekleşmiş olabileceğini düşünülmüştür.

Sonuç Ölümlü tıbbi uygulama hata iddiası bulunan olgularda, ilgili hekim ya da hekimlerin eylemlerinde hatalı olup olmadıkları hususunda görüş bildirilebilmesi için, ölüm sebebinin bilinmesi esas parametrelerdendir. Her ne kadar çalışmamızdaki olgularda tıbbi belgelerden yola çıkılarak ölüm nedeni ve dolayısıyla tıbbi uygulamada hata iddiaları değerlendirilmiş olsa da, olgularımız içinde otopsi yapılmayanlarda belirlenen ölüm nedenleri, aslında ‘kuvvetli bir tahmin’den öteye gitmemektedir. Bunun yanında, çalışmamızda klinik tanı ve -otopsi var olduğunda- otopsi tanısının uyumlu olup olmaması ile tıbbi uygulamada hata yönünde karar verilip verilmemesi arasında anlamlı farklılık tespit edilmiş olması birlikte değerlendirildiğinde, ‘kuvvetli bir tahmin’ ile tespit edilen ölüm sebeplerinin belirlenmesinde klinik verilerin de ciddiyetle değerlendirildiği görülmektedir. Hekimlerin tıbbi uygulamada hata iddialarıyla karşılaşma risklerinin her geçen gün artacağı beklenen bir gerçektir. Bu durumla karşılaşma ihtimalini azaltmanın yolunun, ilgili hekimlerin mesleki bilgi ve becerilerini artırmaları kadar, klinik takip ve müdahalelerdeki dikkatlerini artırmaları olduğu düşünülse de, tıbbi uygulamada hata iddialarının sayısında asıl azalmanın, hekim ve hasta/hasta yakınları arasındaki kişisel ilişkinin kalitesinin artırılması ile sağlanabilineceği de unutulmamalıdır. Çıkar örtüşmesi: Çıkar örtüşmesi bulunmadığı belirtilmiştir.

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ORIGINAL ARTICLE - ABSTRACT OLGU SUNUMU

Evaluation of medical malpractice in emergency and elective general surgery cases resulting in death İbrahim Üzün, M.D.,1 Erdinç Özdemir, M.D.,2 İpek Esen Melez, M.D.,3 Deniz Oğuzhan Melez, M.D.,4 Adem Akçakaya, M.D.,5 The Ministry of Justice Council of Forensic Medicine, İstanbul; Department of Forensic Medicine, Akdeniz University Faculty of Medicine, Antalya-Turkey Muş Branch Office, The Ministry of Justice Council of Forensic Medicine, Muş-Turkey Department of Forensic Medicine, Bezmialem Vakıf University Faculty of Medicine, İstanbul-Turkey 4 The Ministry of Justice Council of Forensic Medicine, İstanbul-Turkey 5 Department of General Surgery, Bezmialem Vakıf University Faculty of Medicine, İstanbul-Turkey 1 2 3

BACKGROUND: General surgery is one of the branches in which the distinction between complication and malpractice is difficult to distinguish. In this study, presentation of the main forensic medical parameters considered for the evaluation of medical malpractice in cases of general surgery deaths in which medical malpractice has been alleged and discussing related concepts through the literature are aimed. METHODS: Allegations of medical malpractice against general surgery physicians sent to the First Forensic Expertise Board of the Council of Forensic Medicine between January 1, 2012 and December 31, 2013 for which the relation of casuality between medical malpractice and death had been determined were retrospectively evaluated. RESULTS: Medical malpractice was ruled in 21.9% (n=23) of 105 cases. The most common primary disease diagnoses were trauma-injury (n=32, 30.5%), cholecystitis (n=25, 23.8%) and appendicitis (n=8, 7.6%). When treatment types were compared according to malpractice decision, rate of malpractice in medicine-only treatment was found to be significantly higher compared to surgery + medical treatment (p=0.003, p<0.01). No statistically significant difference was found regarding the rate of malpractice between cases of emergency and elective surgery (p>0.05). When incidence of medical malpractice was compared between cases with clinical diagnosis and diagnosis determined by autopsy, a statistically significant difference was found (p=0.031, p<0.05). Malpractice was ruled at a significantly lower rate in cases in which diagnosis was confirmed with autopsy (p=0.028, p<0.05). DISCUSSION: It can be concluded that physicians are as successful in emergency conditions as in elective conditions and correct administration of medical treatment is of vital importance. Moreover, the Council of Forensic Medicine considers the clinical follow-up data as well as the autopsy data in medical malpractice evaluation. Keywords: Autopsy; forensic medicine; general surgery; medical malpractice. Ulus Travma Acil Cerrahi Derg 2016;22(4):365–373

doi: 10.5505/tjtes.2015.26543

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ORİJİ N A L Ç A LI Ş M A

Çocuklarda vasküler olmayan dördüncü derece böbrek yaralanmalarında minimal invaziv tedavi yaklaşımları Dr. Ayşe Başak Uçan, Dr. Zehra Günyüz Temir, Dr. Arzu şencan, Dr. Aytaç karkıner, Dr. Hüseyin Evciler Behçet Uz Çocuk Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Çocuk Cerrahisi Kliniği, İzmir

ÖZET AMAÇ: Çocukluk çağında düşük dereceli künt böbrek yaralanmalarında konservatif tedavi yöntemleri kullanılır. Ancak dördüncü derece yaralanmalarda tedavi protokolleri tam olarak belirlenememiştir. Çalışmamızın amacı, kliniğimize ürinom ile başvuran veya üriner ekstravazasyon saptanan hastalarda tedavi yöntemlerini tartışmaktır. GEREÇ VE YÖNTEM: Kliniğimize 2003–2012 yılları arasında başvurmuş olan ve dördüncü derece renal travma saptanmış olan sekiz olgu (K/E=1/7, ortalama yaş: 6 yaş) uygulanan tedavi yöntemleri açısından geriye dönük olarak incelendi. BULGULAR: Dört olguda yüksekten düşme, üç olguda batına künt travma ve bir olguda kereste makinesine sıkışma nedeniyle renal yaralanma vardı. Dört olguda sağ, dört olguda sol renal travma saptandı. Hiçbir olguda hemodinamik instabilite nedeniyle acil eksplorasyon gerekmedi. Bir olgunun ilk incelemelerinde üriner ekstravazasyon gösterilmiş olmasına rağmen izlemde ürinom saptanmadı. Ürinom gelişen yedi olgunun beşi drenaj yöntemleri ile (üç olguda JJ kateter, bir olguda perkütan drenaj (PD) kateteri, bir olguda PD sonrasında JJ kateter yerleştirilerek) tedavi edildi. Geri kalan iki olguda ilk tedavi olarak PD uygulanmasına rağmen üriner sistem bütünlüğünün bozulmuş olması nedeniyle alt pol nefrektomi ve pelviplasti uygulandı. Bir olguya bulguları geriledikten sonra üreteropelvik darlık nedeniyle piyeloplasti uygulandı. Tüm kateterler üriner sistemde ekstravasyon olmadığı gösteridikten sonra çekildi. JJ kateter çekilme süresi ortalama dört ay, PD kateter çekilme süresi 1.5 ay idi. SONUÇ: Çocukluk çağındaki dördüncü derece renal yaralanmalar minimal invaziv yöntemlerle başarıyla tedavi edilebilmektedir. Cerrahi uygulanan olgularda bile öncelikle minimal invaziv yöntemlerin seçilmesi böbreğin korunma şansını artırmaktadır. Anahtar sözcükler: Böbrek travması; çocukluk çağı; ürinom.

GİRİŞ Pediatrik yaş grubundaki böbrek travmalarının %90’ı künt abdominal travma sonucunda meydana gelir. Çocuklar perirenal yağ dokuları az olduğundan ve böbrekleri vücutlarına oranla daha büyük ve mobil olduğundan böbrek travması için yetişkinlerden daha fazla risk altındadırlar.[1] Çocukluk çağındaki künt böbrek yaralanmalarının konservatif yaklaşım ile tedavisinde %87 oranında başarı sağlanabildiği bildirilmektedir.[2] Düşük dereceli yaralanmaların neredeyse tamamı konservatif olarak tedavi edilebilmektedir.[3] Ancak özellikle vasküler olmayan dördürcü derece yaralanmalardaki tedavi protokolleri Sorumlu yazar: Dr. Ayşe Başak Uçan, Behçet Uz Çocuk Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Çocuk Cerrahisi Kliniği, Alsancak İzmir Tel: +90 232 - 411 60 56 E-posta: abasakucan@yahoo.com Ulus Travma Acil Cerrahi Derg 2016;22(4):374–378 doi: 10.5505/tjtes.2015.09514 Telif hakkı 2016 TJTES

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tam olarak belirlenememiştir. Bu tip yaralanmalarda zarar gören renal dokunun yanında üriner kaçak da geliştiğinden morbidite yükselmektedir. Bu çalışmada, travma sonrasında üriner ekstravazasyon saptanan veya izlemde ürinom gelişen olguların tedavi yöntemleri değerlendirildi.

GEREÇ VE YÖNTEM Kliniğimize 2003–2012 yılları arasında başvuran 22 renal travmalı olgudan, dördüncü derece renal travma saptanan sekiz olgu (%36.6); yaş, cinsiyet, yaralanma şekli, hemodinamik durum ve transfüzyon ihtiyacı, böbrekteki fonksiyon kayıpları, uygulanan tedavi yöntemleri (cerrahi, minimal invaziv yöntemler ve konservatif izlem) ve endikasyonları açısından geriye dönük olarak incelendi. Olgulara başvuru anında, rutin idrar incelemesi, hemoglobin değerlerine bakıldı, batın ultrasonografisi (US) ve kontrastlı karın bilgisayarlı tomografisi (BT) çekildi. Böbrek yaralanmalarının derecelendirilmesinde American Association for Ulus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

Uçan ve ark. Çocuklarda vasküler olmayan dördüncü derece böbrek yaralanmalarında minimal invaziv tedavi yaklaşımları

the Surgery of Trauma (AAST) tarafından hazırlanan sistem kullanıldı. Konservatif izlem mesane drenajı, klinik gözlem, yatak istirahati, antibiyotik proflaksisi ve seri hematokrit incelemeleriyle yapıldı. Perkütan drenaj (PD) kateterleri Ege Üniversitesi Girişimsel Radyoloji Bölümü tarafından takıldı. Kateter takıldıktan sonra anterograd grafiler çekilerek ekstravazasyon ve üretere geçiş araştırıldı. 11F sistoskop ile yaş grubuna göre 4F ve ya 4.7F kateter kliniğimizde genel anestezi altında yerleştirildi. Kateterler çekilmeden önce retrograd piyelografi çekilerek ekstravazasyon olmadığı gösterildi. Olguların izleminde US haftalık olarak yapılmış, BT rutin izlemde kullanılmadı. Böbrek fonksiyonları geç dönemde (6. ay) DMSA böbrek sintigrafisi ile belirlendi.

BULGULAR Kliniğimizde tedavi gören sekiz (K/E:1/7) dördürcü derece böbrek travma olgusunun yaş ortalamaları altı (2–9 yaş) yaştı. Dört olguda yüksekten düşme, üç olguda batına künt travma ve bir olguda kereste makinesine sıkışma nedeniyle renal yaralanma gelişmişti. Dört olguda sağ, dört olguda sol renal trav-

ma saptandı. Hiçbir olguda hemodinamik instabilite nedeniyle acil eksplorasyon gerekmedi. Bir olguda iki ünite, üç olguda bir ünite kan transfüzyonu yapıldı. Beş olguda makroskopik, üç olguda mikroskopik hematüri saptandı (Tablo I). Hemodinamik stabilitesi sağlanan olgular konservatif izleme alındı. Bir olguda ekstravazasyon saptandıktan sonra sadece yatak istirahati ve mesane drenajı ile bir hafta sonra ekstravazasyonun kaybolduğu görüldü. İzleme alınan iki olguda 20 ve 25. günde, bir olguda geç dönemde (2. ay) ürinom gelişti. Bir olgu kliniğimize ürinom geliştikten sonra başvurdu (15. gün). Olgularımızda ortalama ürinom gelişme süresi 29 gündü (15–57 gün). Ürinom gelişen dört olgunun tümüne PD kateter takıldı. Bir olgu sadece PD ile sorunsuz olarak iyileşti. Geç dönemde ürinom gelişen olguda alt üriner sisteme geçiş saptanmadığından operasyona alınarak nekrotik alt pol çıkarılarak üreterokalikostomi uygulandı. Bir diğer olguda ekstravazasyon devam ettiği için geç dönemde cerrahi tedavi uygulandı. Ürinom geliştikten sonra başvuran olguda PD kateteri ile tedavi sonrasında minimal ekstravazasyon saptanarak izlemine

Tablo 1. Olguların demografik bulguları, yaralanma biçimleri, hematüri varlığı ve tranfüzyon ihtiyacı gösterilmiştir

Cinsiyet

Yaş (yıl)

Transfüzyon ihtiyacı

Yaralanan taraf

Hematüri

Travma oluş biçimi

Olgu 1

Erkek

–

Sol

Makroskobik

Batına künt travma

Olgu 2

Erkek

–

Sağ

Makroskobik

Batına künt travma

Olgu 3

Erkek

1 Ü

Sol

Makroskobik

Yüksekten düşme

Olgu 4

Erkek

1 Ü

Sol

Mikroskobik

Yüksekten düşme

Olgu 5

Erkek

2 Ü

Sol

Mikroskobik

Yüksekten düşme

Olgu 6

Erkek

–

Sağ

Mikroskobik

Batına künt travma

Olgu 7

Kız

1 Ü

Sağ

Makroskobik

Yüksekten düşme

Olgu 8

Erkek

–

Sağ

Makroskobik

Sıkışma

Tablo 2. Olgulara uygulanan tedavi yöntemleri ve uygulama zamanları

Başvuru anında BT’de ekstravazasyon

Ürinom gelişme süresi

Kateter takılma zamanı

Kateter kalış süresi

Böbrek fonksiyonu (%)

Cerrahi tedavi

Olgu 1

Var

–

3. gün ( JJ)

4 ay

Pyeloplasti (AH)

Olgu 2

Var

–

Olgu3

Yok

57 gün

61. gün (PD)

1 ay

–

Üreterokalikostomi+ alt pol heminefrektomi

Olgu 4

Yok

20 gün

27. gün (PD)

1 ay

Olgu 5

Var

–

13. gün ( JJ)

4 ay

Olgu 6

Ürinom var

15 gün

16. gün (PD+JJ)

2 ay, 2 ay

Olgu 7

Var

–

6. gün ( JJ)

6 ay

Olgu 8

Yok

25 gün

30. gün (PD)

2 ay

Pelvik onarım

29 gün

PD: 33 gün

PD: 1.5 ay

33.3

JJ: 7 gün

JJ: 4 ay

Ortalama

AH: Anderson – Hynes Pyeloplasti; PD: Perkütan drenaj.

Ulus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

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(a)

(b)

(c)

(d)

Şekil 1. (a) Olgu 6 geniş ürinom ile başvurdu. (b) Olgu 5 travma sonrası 10. günde ekstravazasyon saptandı. (c) Olgu1 UPD zemininde ekstravazasyon ve hematom saptandı. (d) Olgu 7, üç yıl önce geçirilmiş böbrek travması, sol böbrek nonfonksiyone, sağ böbrekte yeni geçirilmiş travmaya bağlı hematom ve ekstravazasyon.

JJ kateter ile devam edildi ve cerrahi tedavi gerekli olmadı (Şekil 1a). Üç olguya başvuru anında ekstravazasyon saptanarak hemodinamik stabilizasyon sonrası erken dönemde JJ kateter yerleştirildi. Olgulardan birinde soliter böbrek (Şekil 1d) diğer olguda üreteropelvik darlık (UPD) mevcuttu (Şekil 1c). Üçüncü olgu kliniğimize travma sonrası geç dönemde (10. gün) başvurdu ve BT’de ekstravazasyonun devam ettiği saptanarak JJ kateter yerleştirildi (Şekil 1b). Her üç olguda tedavi sağlanırken birinde UPD nedeniyle travma sonrası geç dönemde pyeloplasti uygulandı. PD kateter takılan olgularda kateterin çekilme süresi ortalama 1.5 ay, JJ kateter takılan olgularda ortalama dört aydı (Tablo 2). Stentler çıkartılmadan önce ekstravazasyonun kaybolduğu radyolojik olarak gösterildi. Kateterlerin takılması ve ya çıkartılması sırasında herhangi bir komplikasyon görülmedi. Kateter takılan tüm olgularda antibiyotik proflaksisi uygulandı. Hastaların izleminde tedavi sonrası altıncı ayda DMSA yapıldı. Ortalama diferansiyel böbrek fonksiyonları %33.3 (%16–%44) olarak belirlendi. En düşük fonksiyon UPD saptanan olguda, en yüksek fonksiyon konservatif olarak tedavi edilebilen olguda saptandı. Hiçbir olguda iki yıllık izlemde geç komplikasyon veya hipertansiyon saptanmadı.

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TARTIŞMA Vasküler olmayan dördüncü derece böbrek yaralanması saptanan olgularda tedavi yöntemleri çok iyi belirlenmemiştir. Nonoperatif tedavi son yıllarda pek çok merkezde uygulanmaya başlamıştır. Ancak kullanılacak konservatif tedavinin, minimal invaziv yöntemlerin ne zaman, hangi hastaya, hangisi seçilerek uygulanacağı belirgin değildir. Girişim oranları %9–%45 gibi geniş aralıklarda bildirilmektedir.[4–7] İngilizce literatürde yayınlanmış serilerin değerlendirildiği bir derleme makalede, toplamda 95 olgunun bildirildiği ve yalnızca 13 (%14) olgunun minimal invaziv yöntemlerle tedavi edildiği yayınlanmıştır.[7] Yirmi yedi olguluk çalışmada, konservatif olarak izlenen yalnızca üç olguda JJ stent yerleştirildiği ve sadece bir olguda ürinom geliştiği bildirilmiştir.[5] Ancak bu çalışmada olguların hastanede kalış süreleri ortalama sekiz gün olarak belirtilmiş ve kontrollerine ait bilgi verilmemiştir. Olgularımızda ortalama ürinom gelişme süresi 29 gündür (15–57 gün) ve girişim oranları yüksek görünmektedir. Sadece bir olgu konservatif izlemde iyileşmiş, dört olguda ürinom gelişmiş (%50), üç olguya (%37.5) ürinom gelişimi beklenmeksizin erken dönemde JJ kateter yerleştirilmiştir. Bunun nedeni daha hafif seyirli Ulus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

Uçan ve ark. Çocuklarda vasküler olmayan dördüncü derece böbrek yaralanmalarında minimal invaziv tedavi yaklaşımları

olguların periferdeki merkezlerde izlenmesi, acil operasyona alınan olgu bulunmaması, üç olguda erken dönemde kateter yerleştirilmesi olabilir. Erken kateter yerleştirilme endikasyonları bir olguda UPD, bir olguda tek böbrek, bir olguda geç başvuruya rağmen ekstravazasyonun devam etmesidir. Cannon ve ark., ürinom gelişimini saptamak için erken dönemde, travmadan 48 saat sonra BT tekrarını önermişlerdir. Ancak yine aynı seride 48. saatteki BT görüntülerinde ekstravazasyonda artma saptanmayan olgularda da ürinom gelişebildiğini bildirilmişlerdir. Aynı çalışmada hangi hastada ürinom gelişeceğinin BT bulgularına göre değerlendirilmesi araştırılmış, üretere geçişin olmamasının erken minimal invaziv yöntemler için endikasyon oluşturabileceği belirtilmiştir.[8] Batın tomografi bulgularına dayanılarak erken JJ stent yerleştirilen olgularda hastanede kalım süresinin kısaldığı ve morbiditenin azaldığı belirtilmiştir. Alsikafi ve ark. tarafından ikinci BT’nin üç-yedi günlerde çekilmesi ve ekstravazasyonun devam etmesi halinde internal stent yerleştirilmesi önerilmiştir.[5] Kliniğimizde izlenen ve ürinom gelişen üç olgumuzda başvuru sırasındaki BT imajlarında ekstravazasyon görüntülenememiştir. Bunun nedeni olarak incelemelerin acil koşullarda geç imajlar alınmaksızın yapılması ve hematom bulgularının ilk dönemde daha baskın olması düşünülebilir. Çocukluk yaş grubunda travma tedavisinin büyük oranda konservatif olduğu düşünülerek hemodinamik stabilite sağlandıktan sonra ilk çekilen BT’nin fazla zaman ayrılarak üretere geçiş ve ekstravazasyon açısından daha iyi değerlendirilmesi sağlanmalıdır. Olgularımızda klinik bulgularda değişiklik olmaması halinde ürinom izlemi haftalık US ile yapılmış rutin olarak ikinci bir BT çekilmemiştir. Ultrasonografi noninvaziv bir yöntem olmakla birlikte olgularımızın erken dönemde BT ile değerlendirilmemiş olması ekstravazasyonun gözden kaçmasına ve ürinom ile geç dönemde başvurmalarına neden olmuş olabilir. Olgularımızda ortalama ürinom gelişme süresi 29 gündür (15–57 gün). Literatürde travmadan üç ay sonra ürinom gelişerek başvuran bir olgu bildirilmiştir.[9] Bizim geç dönemde (57. gün) başvuran olgumuzda alt polde nekroza giden böbrek dokusunun ve gelişen skar dokusunun basısı ile üretere geçişin engellendiği görülmüştür. Rogers ve ark. üriner ekstravazasyonun 15 günden uzun süre devam etmesi halinde üreteral stent yerleştirilmesini önermişlerdir.[6] Bir olgumuzda travma sonrası 10. günde ekstravazasyonun devam ettiği ancak ürinom gelişmediği düşünülürse, izlemin ilk haftası tamamlandıktan sonra (7–10 gün) kontrol BT çekilmesi uygun olabilir. Bir haftalık periyotun, olguların ekstravazasyonlarının gerileyip gerilemediğinin daha kolay değerlendirilmesinde de yararlı olabileceği düşünülebilir. Yine de ekstravazasyonun miktarı bu zamanlamayı etkileyen temel faktördür ve her hastada standart değildir. Yüksek debili olgularda semptomların ortaya çıkması erken BT için endikasyon kabul edilebilir.

İzlemde ürinom gelişen olgularda, ürinomun kısa sürede boşalmasını sağlayarak morbidite riskini azaltmada daha etkili olacağı düşünülen PD yöntemi kullanılmıştır. Perkütan drenaj sonrasında anterograd grafilerle üretere geçiş olup olmaması ve uzun dönem üriner ekstravazasyonun devam edip etmemesi araştırılmıştır. Bir olguda PD ile ekstravazasyonun tamamen kaybolduğu saptanırken, bir olguda minimal ekstravazasyon saptanmış ve kateteri çekilerek JJ kateter yerleştirilmiş, bu olguda cerrahi girişim gerekmemiştir. Cerrahi uygulanan iki olguda, cerrahi öncesi ürinomun boşaltılması, semptomların gerilemesi ve hastanın stabilizasyonunun sağlanması açısından PD kateterin yerleştirilmesi yarar sağlamıştır. Başvuru sonrasında ekstravazasyon saptanan olgularda konservatif tedavi ile ürinomun oluşup oluşmayacağının beklenmesi yerine üç olgumuzda erken dönemde JJ kateter takılmıştır. JJ katetere bağlı komplikasyon görülmemesi, kısa süreli anestezi ile takılabilmesi, erken taburcu imkanı sağlaması, dördüncü derece böbrek yaralanmalarında erken dönemde, özellikle de riskli olgularda tercih edilebilecek bir yöntem olduğunu ve ürinom gelişmesini önleyerek morbiditeyi azalttığını düşündürmektedir.[8] Olgularımızdan birinde rölatif acil operasyon endikasyonu sayılan UPD saptanmıştır. Bu olguda acil cerrahi yerine JJ kateter yerleştirilmiş ve geç dönemde cerrahi tedavi uygulanmıştır. Cerrahi onarım sırasında bu olgularda erken dönemde rapor edilen ödem, hematom, yapışıklık gibi bulguların ortadan kalkmış olduğu görülmüştür. Erken dönemdeki operasyonun daha zor koşullarda gerçekleştirildiği ve nefrektomi ile sonuçlanabildiği rapor edilmiştir.[10,11] Üreteropelvik darlık olgularında tanının gecikmesinin de nefrektomi ile sonuçlandığı bildirilmiştir.[7] Hemodinamik instabilite olmaması durumunda UPD olgularında erken drenaj ile hem hasta hem de cerrah için daha konforlu bir operasyon gerçekleştirilebilir.[7,11] Ürinom geliştikten sonra debisinin daha az olması nedeniyle ürinomun tam olarak boşaltılmasında JJ kateter etkin olmayabilir. Bu durum enfeksiyona eğilim yaratabilir ve semptomların kateter takıldıktan sonraki dönemde devam etmesi ile sonuçlanabilir. Ürinomun gelişmesinden sonra tercih edilecek yöntem PD ve ürinom boşaltıldıktan sonra JJ kateter takılması olabilir. JJ ile kateterizasyonun kullanımını kısıtlayan bir başka neden ise distal üreterde bizim de bir olgumuzda saptandığı gibi üreteral obstrüksiyon gelişmesidir. Olgularımızın tedavi sonrası renal fonsiyonları altıncı ayda DMSA kullanılarak belirlenmiştir. Öncesinde UPD mevcut olduğu düşünülen bir olgu hariç (%16) diğer tüm olgularda böbrek fonksiyonlarının %30’un üzerinde saptanmış olması tedavi yaklaşımımız açısından olumlu bir faktör olarak kabul edilebilir. Ancak yine de differansiyal fonksiyonların değerlendirilmesinde, travmadan kaynaklanan kayıp ile tedavi kaynaklı düzelme oranlarının ayrıştırılarak bir sonuca varılması zordur. Sonuç olarak, vasküler olmayan dördüncü derece böbrek ya-

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ralanmalarında minimal invaziv yöntemler etkin bulunmuştur. İzlemde ürinom gelişen olgularda PD kateteri takılması hem tedavi edici olabilir hem de semptomları ortadan kaldırır. Cerrahi gerektiren olgularda, cerraha zaman kazandırıp daha konforlu bir operasyon sağlayarak böbrek kayıplarını azaltabilir. JJ kateter üriner ekstravazasyon saptanan özellikli olgularda (soliter böbrek, UPD) ve ekstravazasyonu devam eden olgularda ürinom gelişim riskini önlemek için seçilecek ilk yöntem olabilir. Erken dönemde kateter yerleştirilmesi kararını verebilmek için izlemin ilk haftası tamamlandıktan sonra çekilecek BT’nin yararlı olabileceği düşünülmüştür. Bu yaklaşımın geniş çalışmalarda ileriye yönelik olarak değerlendirilmesi gereklidir. Çıkar örtüşmesi: Bildirilmedi.

KAYNAKLAR 1. Brown SL, Elder JS, Spirnak JP. Are pediatric patients more susceptible to major renal injury from blunt trauma? A comparative study. J Urol 1998;160:138–40. 2. Margenthaler JA, Weber TR, Keller MS. Blunt renal trauma in children: experience with conservative management at a pediatric trauma center. J Trauma 2002;52:928–32.

3. Roelants-van Rijn AM, Groenendaal F, Stoutenbeek P, van der Grond J. Lactate in the foetal brain: detection and implications. Acta Paediatr 2004;93:937–40. 4. Buckley JC, McAninch JW. Pediatric renal injuries: management guidelines from a 25-year experience. J Urol 2004;172:687–90. 5. Alsikafi NF, McAninch JW, Elliott SP, Garcia M. Nonoperative management outcomes of isolated urinary extravasation following renal lacerations due to external trauma. J Urol 2006;176:2494–7. 6. Rogers CG, Knight V, MacUra KJ, Ziegfeld S, Paidas CN, Mathews RI. High-grade renal injuries in children--is conservative management possible? Urology 2004;64:574–9. 7. Umbreit EC, Routh JC, Husmann DA. Nonoperative management of nonvascular grade IV blunt renal trauma in children: meta-analysis and systematic review. Urology 2009;74:579–82. 8. Cannon GM Jr, Polsky EG, Smaldone MC, Gaines BA, Schneck FX, Bellinger MF, et al. Computerized tomography findings in pediatric renal trauma--indications for early intervention? J Urol 2008;179:1529–33. 9. Chu C, Chen K, Ou T. Delayed presentation of a posttraumatic perirenal urinoma in a 6-year-old boy. Pediatr Surg Int 2000;16:140–1. 10. Boone TB, Gilling PJ, Husmann DA. Ureteropelvic junction disruption following blunt abdominal trauma. J Urol 1993;150:33–6. 11. Onen A, Kaya M, Cigdem MK, Otçu S, Oztürk H, Dokucu AI. Blunt renal trauma in children with previously undiagnosed pre-existing renal lesions and guidelines for effective initial management of kidney injury. BJU Int 2002;89:936–41.

ORIGINAL ARTICLE - ABSTRACT OLGU SUNUMU

Minimally invasive theurapeutic approaches in pediatric nonvascular fourth-grade renal trauma Ayşe Başak Uçan, M.D., Zehra Günyüz Temir, M.D., Arzu Şencan, M.D., Aytaç Karkıner, M.D., Hüseyin Evciler, M.D. Department of Pediatric Surgery, Behçet Uz Children Hospital, İzmir-Turkey

BACKGROUND: Conservative management procedures are implemented in cases of low-grade pediatric blunt renal trauma, but procedures for grade 4 injuries are not clearly defined. The present objective was to discuss treatment procedures in patients who presented with or developed urinoma during follow-up. METHODS: Treatment procedures implemented in 8 patients (female:male ratio=1:7; average age: 6) with grade 4 renal trauma who presented to the clinic between 2003 and 2012 were retrospectively analyzed. RESULTS: Cause of renal injury was fall in 4 cases, blunt abdominal trauma in 3 cases, and being trapped in a harvesting machine in 1 case. Right renal trauma was diagnosed in 4 cases, left renal trauma in 4. Emergent exploration due to hemodynamic instability was not necessary. Although urinary extravasation was observed upon investigation in 1 patient, urinoma did not form during follow-up. Five of the 7 patients with urinoma were treated with drainage procedures (double-J catheter ( JJ) in 3, percutaneous drainage (PD) in 1, followed by JJ catheter placement). In spite of initial PD, inferior pole nephrectomy and pyeloplasty were performed in the remaining 2 cases due to decomposition of the integrity of the urinary system. In 1 patient, pyeloplasty was performed following regression of symptoms due to ureteropelvic obstruction. Catheters were removed when extravasation was not detected in the urinary system. Average time of removal was 4 months for JJ catheters and 1.5 months for PD catheters. DISCUSSION: Pediatric grade 4 renal trauma can be successfully treated with minimally invasive procedures. Initial implementation of these procedures increases the chance of kidney salvage, even when surgical intervention is eventually performed. Keywords: Children; renal trauma; urinoma. Ulus Travma Acil Cerrahi Derg 2016;22(4):374–378

378

doi: 10.5505/tjtes.2015.09514

Ulus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

ORİJİ N A L Ç A LI Ş M A

Proksimal humerus çok parçalı kırıklarında plak osteosentez ve hemiartroplasti sonuçlarının orta dönem takip ile değerlendirilmesi Dr. Cem Çelik,1 Dr. Seyit Ali Gümüştaş,2 Dr. Gültekin Sıtkı Çeçen,3 Dr. Güven Bulut,3 Dr. Halil İbrahim Bekler3 1

Geyve Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Sakarya

Yavuz Selim Kemik Hastalıkları ve Rehabilitasyon Hastanesi, Ortopedi ve Travmatoloji Kliniği, Trabzon

Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul

ÖZET AMAÇ: Bu çalışmada, fiksasyon veya hemiartroplasti ile tedavi edilmiş olan parçalı proksimal humerus kırıklarında hastaların fonksiyonel sonucuna etki eden faktörleri geriye dönük olarak değerlendirmeyi amaçladık. GEREÇ VE YÖNTEM: Çalışmamıza 2007–2012 yılları arasında kliniğimizde Neer tip 3 ve 4 proksimal humerus kırığı nedeniyle ameliyat edilen ve ameliyat sonrası en az iki yıl takibi sürdürülen 58 (19 kadın, 39 erkek; ort. yaş; 51.04 yıl; dağılım 22–78 yıl) hasta dahil edildi. Hastaların 35’ine açık redüksiyon ve anatomik plak fiksasyon, 23’üne parsiyel omuz protezi uygulandı. Hastalar son kontrollerinde Constant-Murley’in omuz skorlamasına göre değerlendirildi. Hastaların yaş, cinsiyet, ASA skoru, travma enerjisi, kırık tipi ve ameliyat öncesi sürenin fonksiyonel sonuçlar üzerine etkisi incelendi. BULGULAR: Hastalar ortalama 47.25±13.29 (25–76) ay takip edildi. Hastaların tümünde ortalama Constant-Murley puanı 58.65±18.62 olarak tespit edildi. Fonksiyonel puan fiksasyon grubunda 65.77±18.67 iken, hemiartroplasti grubunda 47.82±12.52 olarak saptandı (p=0.001). Bağımsız değişkenlerin birden fazlasının fonksiyonel sonuçlara etkisi incelendiğinde, fiksasyon grubunda ASA skoru ve kırık tipi, hemiartroplasti grubunda ise travma enerjisi ile fonksiyonel sonuçları anlamlı düzeyde etkilediği tespit edildi. Son takipte 20 hastada (%34.5) komplikasyon saptandı ve bunların 14’ü (%70) rotator cuff yetmezliğiydi. SONUÇ: Çok parçalı proksimal humerus kırıklarının cerrahi tedavisinde plak fiksasyonu ile daha yüksek fonksiyonel sonuç elde edilebilirken her iki cerrahi yöntemde rotator cuff yetmezlik oranının yüksek oluşu göz önünde bulundurulmalıdır. Anahtar sözcükler: Cerrahi; parçalı kırık; proksimal humerus; sonuçların değerlendirilmesi.

GİRİŞ Proksimal humerus kırıkları tüm kırıkların %5’ini, humerus kırıklarının %45’ini oluşturmaktadır.[1] Üç ve dört parçalı proksimal humerus kırıkları ise tüm proksimal humerus kırıklarının %13–16’sını oluşturur.[2] Proksimal humerus kırıkları sıklıkla osteoporotik yaşlı hastalarda düşük enerjili travma ile, genç hastalarda ise yüksek enerjili travma ile oluşur.[3] Toplumun

yaş ortalamasının artışı ve osteoporozlu insan sayısındaki artış, proksimal humerus kırıklarının görülme sıklığını da artırmıştır. [4] Proksimal humerus kırıklı hastaların yaklaşık %80’inde deplasman hiç yoktur ya da minimaldir ve konservatif tedavi uygulanır, %20 kadarında ise deplasman veya instabilite mevcuttur ve cerrahi tedavi gerekmektedir.[5] Üç ya da dört parçalı kırıklarda, açık redüksiyon-plak osteosentezi ya da hemiartroplasti güncel olarak en sık uygulanan tedavi seçenekleridir fakat en uygun cerrahi yöntem halen tartışılmaktadır.[6]

Sorumlu yazar: Dr. Seyit Ali Gümüştaş, Yavuz Selim Kemik Hastalıkları ve Rehabilitasyon Hastanesi, Ortopedi ve Travmatoloji Kliniği, 61030 Trabzon Tel: +90 462 - 322 11 40 E-posta: seyitali_gumustas@yahoo.com Ulus Travma Acil Cerrahi Derg 2016;22(4):379–385 doi: 10.5505/tjtes.2016.90402 Telif hakkı 2016 TJTES

Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

Çok parçalı proksimal humerus kırıklarında hastaların fonksiyonel sonucuna etki edebilecek faktörleri ameliyat öncesi değerlendirip gerekli önlemleri alarak tedaviden alınacak başarı sonucunu artırabileceğimiz düşüncesiyle bu çalışmada, açık redüksiyon-plak fiksasyonu veya hemiartroplasti ile tedavi edilmiş olan Neer tip 3 ve 4 proksimal humerus kırıklarında hastaların fonksiyonel sonucuna etki edebilecek faktörlerin geriye dönük olarak değerlendirilmesi amaçlandı. 379

Çelik ve ark. Proksimal humerus çok parçalı kırıklarında plak osteosentez ve hemiartroplasti sonuçları

dreni birinci gün çekildikten sonra omuz sarkaç egzersizleri ile birlikte el bileği ve dirsek aktif hareketlerine başlandı. Fiksasyon grubunda pasif hareketlere üçüncü günde, artroplasti grubunda ise stürler alındıktan sonra (ikinci haftada) başlandı. Her iki grupta aktif hareketlere radyolojik olarak kaynama ortaya konduktan sonra ortalama yedinci (5–9) haftada başlandı. (Protez grubunda tüberküllerin şafta kaynaması baz alındı).

GEREÇ VE YÖNTEM Çalışmamız için 2007–2012 yılları arasında kliniğimizde Neer tip 3 ve 4 proksimal humerus kırığı nedeniyle ameliyat edilen 76 hasta geriye dönük olarak incelendi. Travma sonrası iki haftadan fazla süre geçmiş, ASA 4 ya da 5, patolojik kırık, hayatı tehdit eden iç organ yaralanması, öncesinde omuz çevresi ameliyat öyküsü, iki yıldan az takip süresi olan ve travma öncesi ekstremitelerini aktif kullanamayan hastalar çalışma dışında tutuldu. Belirlenen kriterlere uyan 58 hasta çalışmaya dahil edildi. Hastaların 33’ünde düşük (düz zeminde düşme), 25’inde yüksek (9 hasta araç içi, 7 hasta araç dışı trafik kazası, 6 hasta yüksekten düşme, 3 hasta motosiklet kazası) enerjili travma sonrası kırık gelişmişti. Hastaların 13’ünde proksimal humerus kırığına ek olarak ekstremite yaralanması (9 alt, 3 üst, 2 vertebra) mevcuttu. Hastaların cerrahi gruplara göre ve genel dağılımı Tablo 1’de özetlenmiştir.

Hastalar son kontrollerinde Constant-Murley’in omuz skorlamasına[8] göre ağrı, günlük yaşam aktivitesi, hareket açıklığı ve kuvvet yönünden, toplam 100 puan üzerinden değerlendirildi. Buna göre, 100–80 puan arası çok iyi, 79–60 puan arası iyi, 59–40 puan arası orta, 39–20 puan arası kötü, 19–0 puan arası çok kötü olarak değerlendirildi.

İstatistiksel Analiz Verilerin istatistiksel analizi SPSS 17.5 istatistik paket programı kullanılarak yapıldı. Kategorik değişkenlerin karşılaştırılmasında kikare testi kullanıldı. Normal dağılan sürekli değişkenlerin karşılaştırılması T testi ile, normal dağılmayan sürekli değişkenlerin karşılaştırılması Mann-Whitney U-testi ile yapıldı. Birden fazla değişkenin sonuç üzerine etkisi regresyon analizi ile değerlendirildi. Tüm analizlerde p<0.05 istatistiksel anlamlı değer olarak kabul edildi.

Hastalarımıza ameliyat öncesi omuz gerçek ön-arka ve yan grafi rutin olarak çekilmişti. Direkt grafiye ek olarak 17 hastada (%29.3) bilgisayarlı tomografi ihtiyaç duyulmuştu. Ameliyatların tümü genel anestezi altında, şezlong pozisyonunda, deltopektoral insizyonla yapıldı[7] ve deltoidin klavikular yapışma yerinin kemikten sıyrılmadan ekspojur sağlanmasına özen gösterildi. Hastaların tümünde cerrahi esnasında skopi görüntüsü elde edildi. Açık redüksiyon ve fiksasyon grubunda anatomik, kilitli titanyum plak (TST Orthopaedics, Pendik, Türkiye), artroplasti grubunda çimentolu parsiyel omuz protezi (TST Orthopaedics, Pendik, Türkiye) kullanıldı. Hastaların hepsine ameliyat sonrası velpeau bandajı uygulandı. Yara yeri

BULGULAR Hastaların tümü ortalama 47.25±13.29 (25–76) ay takip edildi. Takip süresi açık redüksiyon ve kilitli plak fiksasyon grubunda 46.50±13.91 (25–74) ay iken, hemiartroplasti grubunda 48.0±13.92 (26–76) ay olarak tespit edildi.

Tablo 1. Hastaların cerrahi gruplara göre ve genel dağılımı Yaş

Protez 60.26±13.86

ARİF 45.02±16.30

Toplam

0.001* 51.06±17.0

Cinsiyet

Kadın

5 (21.7)

14 (40)

0.14

Erkek

18 (78.3)

21 (60)

19 (32.7) 39 (67.3)

ASA

ASA 1

5 (21.7)

ASA 2

3 (13)

ASA 3

15 (65.2)

15 (42.9)

20 (34.6)

16 (45.7)

19 (32.7)

0.001*

4 (11.4)

19 (32.7)

Travma enerjisi

Düşük

19 (82.6)

14 (40)

0.001*

Yüksek

4 (17.4)

21 (60)

33 (56.9) 25 (43.1)

Kırık tipi

Tip 3

Tip 4

Ameliyat öncesi süre (gün)

13 (56.5) 10 (43.5) 10.56±3.42

25 (71.4)

0.001*

10 (28.6) 5.11±2.71

38 (65.5) 20 (34.5)

0.001* 7.27±4.02

*p<0.05.

380

Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

Çelik ve ark. Proksimal humerus çok parçalı kırıklarında plak osteosentez ve hemiartroplasti sonuçları

Hastaların tümünde ortalama Constant-Murley puanı 58.65±18.62 olarak tespit edildi. Fiksasyon grubunda 65.77±18.67 olarak tespit edilen Constant-Murley puanı, hemiartroplasti grubunda 47.82±12.52 olarak saptanan puana göre anlamlı olarak yüksek tespit edildi (p=0.001). Hastaların yaşı, cinsiyeti, ASA skoru, travma enerjisi, kırık tipi ve travmadan ameliyata kadar geçen süre ile Constant-Murley

skorlama arasındaki ilişki değerlendirdiğinde fiksasyon grubunda yaş, ASA skoru ve kırık tipi, hemiartroplasti grubunda ise cinsiyet, ASA skoru, travma enerjisi ve kırık tipi ile anlamlı istatistiksel ilişki saptandı (Tablo 2). Anlamlı ilişki tespit edilen değişkenlerin hepsinin birden etkisi doğrusal regresyon analizi ile incelendiğinde fiksasyon grubunda ASA skoru ve kırık tipi, hemiartroplasti grubunda ise travma enerjisi ile fonksiyonel skor arasında anlamlı istatistiksel ilişki ortaya çıktı (Tablo 3).

Tablo 2. Değişkenlere göre fonksiyonel sonuçların grup içinde değerlendirilmesi

Protez grubu

C-M puan

ARİF grubu p

C-M puan

75.65±16.62

0.021*

Yaş

<55 yaş

≥55 yaş

52.80±16.80

0.14

44.0±6.28

54.50±17.71

Cinsiyet Kadın Erkek

39.2±7.52

0.041*

63.85±15.02 0.45

50.22±12.72

67.04±21.01 77.60±13.88

ASA

ASA 1

58.40±18.74

ASA 2

58.0±12.12

ASA3

0.043 *

58.75±15.99 0.002*

42.26±5.48

49.50±21.36

49.89±12.80

66.14±17.07 0.91

Travma enerjisi Düşük Yüksek

0.008*

38.0±3.6

65.52±20.07

Kırık tipi

Tip 3

52.46±14.8

0.015*

Tip 4

41.8±4.49

73.28±12.62 0.001* 47.0±18.53

Ameliyat öncesi süre

<7 gün

44.50±4.04

0.57

≥7 gün

48.52±13.64

65.85±18.93

0.96

65.50±19.01

C-M: Constant Murley. *p<0.05.

Tablo 3. Fonksiyonel sonucu anlamlı etkileyen değişkenlerin doğrusal regresyon analizi

Beta (korelasyon katsayısı)

Protez grubu Cinsiyet

13.592

1.900

0.074

ASA

-5.079

-1.257

0.22

Kırık tipi

3.013

.434

0.67

Travma enerjisi

-25.553

-2.302

0.033*

ARİF grubu Yaş

-.092

-.449

0.65

ASA

-9.068

-2.289

0.029*

-19.751

-3.380

0.002*

Kırık tipi

*p<0.05.

Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

381

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Son takipte toplamda 20 hastada (%34.5) komplikasyon saptandı ve bunların 14’ü (%24.1) rotator cuff yetmezliğiydi. Plak uyguladığımız 35 hastamızın 11’inde (%31.4) (5 rotator cuff yetmezliği, 4 varus açılanması, 2 avasküler nekroz), hemiartroplasti uyguladığımız 23 hastamızın dokuzunda (%39.1) (tümünde rotator cuff yetmezliği) komplikasyon gelişti (p=0.54). Komplikasyon gelişen hastalardan sadece fiksasyon grubunda avasküler nekroz gelişen iki hastaya ikincil cerrahi olarak hemiartroplasti uygulandı.

TARTIŞMA Parçalı proksimal humerus kırıklarının tedavisinde, kırığın fiksasyonu ya da hemiartroplasti uygulanmasına karar verilmesi önemli ve güçtür. Bu kararda, kırık tipi ile birlikte cerrahın deneyimi, hastanın yaşı ve kemik kalitesi belirleyici rol oynar.[9] Neer tip 3 ve 4 proksimal humerus kırıklarında açık redüksiyon ve internal fiksasyon genç ve osteoporozu olmayan hastalarda tercih edilmesi gereken cerrahi seçenek olarak bulunurken, yaşlı ve osteoporozu olan hastalarda artroplasti seçeneğinin daha uygun olduğu bildirilmiştir.[10,11] Kliniğimizde proksimal humerus kırıklarında cerrahi seçeneği belirlerken literatür ile uyumlu olarak yaş kriteri göz önüne alınmaktadır. Çalışmamızda hemiartroplasti uygulanan hastaların ortalama yaşı fiksasyon grubuna göre anlamlı oranda yüksek bulunmuştur. Cerrahi yaklaşımın belirlenmesi ve ameliyatın planlanmasında ameliyat öncesi yeterli radyografik inceleme son derece önemlidir.[12] Bununla birlikte ameliyat esnasında skopinin uygun açıda kullanılmamasının bile komplikasyonlara neden olabileceği gösterilmiştir.[12] Kliniğimizde plak ile fiksasyon esnasında redüksiyonu, plağın üst ucunun yerleşimini ve eklem içi vida penetrasyonunu görmek için, hemiartroplasti uygulanımında ise humerus başının büyüklüğü, yüksekliği ve T.majusun yerleşiminin kontrolü için cerrahi sırasında rutin skopi görüntüsü rutin olarak kullanılmaktadır.

Plak uyguladığımız hastalardan beşinde (%14.3) rotator cuff yetmezliği saptadık. Biz; bu hastalarda kırık tipinin (4 hasta tip 4 kırık nedeniyle opere edilmişti) rotator cuff yetmezliğinde etkili olabileceğini düşünmekteyiz. Ameliyat öncesi manyetik rezonans görüntülemesi (MRG) yapılmadığı için bu durumun, travmaya bağlı ya da cerrahi gerekçelerden hangisinden kaynaklandığı net olarak ortaya konulamamıştır. Ong ve ark.nın çalışmasında proksimal humerus kırığı nedeniyle cerrahi tedavi uygulanan hastaların 13’ünde (%21) komplikasyon (en sık vida penetrasyonu-%11) gelişmiş ve dokuz hastaya (%14.3) ek cerrahi tedavi uygulanmıştır.[18] Çalışmamızda hiçbir olguda vida penetrasyonu ile karşılaşılmamıştır. Ameliyat esnasında uygun pozisyonda ve farklı rotasyonlarda alınan skopi görüntülerinin bu komplikasyondan kaçınmakta etkin olduğunu düşünmekteyiz. Varus kırıklarında fiksasyonun elde edilmesi ve korunması zordur. Bu nedenle bu tip kırıklarda anatomik redüksiyona destek olarak greftleme ve kalkara giden ilave vida düşünülmelidir.[19] Çalışmamızdaki dört (%11.4) hastada varus açılanması komplikasyonu ile karşılaştık. Ameliyat öncesi hastaların birinde düşük enerjili travma sonrası gelişen tip 3 kırık, üçünde yüksek enerjili travma sonrası gelişen tip 4 kırık mevcuttu. Her üç kırıkta metafizer bölgede parçalanma mevcuttu ve operasyon esnasında desteklenmemişti (Şekil 1). Takip grafileri tekrar gözden geçirildiğinde bu kırıkların zamanla varusa gittiği tespit edildi. Humerus proksimal kırıklarında minimal invaziv yöntemle yapılan tespitlerde AVN oranı daha düşüktür. Gardner ve ark. [19] bir kadavra çalışmasında, anterolateral akromiyal yaklaşım ile plağın güvenli bir bölgede ve humerus başının beslenmesine zarar vermeden yerleştirilebileceğini göstermişlerdir.[20] Bu güvenli bölge, proksimal humerusun lateral yüzeyinde, büyük

Proksimal humerus kırıklarının tedavisinde kilitli anatomik plak sıklıkla uygulanan bir yöntem olup, bu uygulama ile yüksek kaynama ve memnuniyet elde edilebilmektedir.[13] Cerrahi teknikte çok dikkat edilmesi gereken başlıca noktalar, plağın tekniğe uygun yerleştirilmesi, vida boylarının skopi kontrolü ile seçilip yerleştirilmesi, başa yeterli pozisyonda ve sayıda vida gönderilmesi, varus yer değiştirmesinin önlenmesi için medial korteks desteğinin sağlanmasıdır.[14] Bu implantların avantajları başlıca anatomik redüksiyonu sağlama esnasında kırık fragmanlarının beslenmesinin daha az bozulması, rotator manşet bütünlüğünü koruma uygun stüryerlerinin bulunması, önemli derecede parçalanma ve osteporoz varlığında farklı açılarda vida göndermeye olanak sağlayarak stabil fiksasyon elde etmedir.[15] Bununla birlikte bu uygulamada yüksek komplikasyon oranları bildiren çalışmalar da mevcuttur. Eklem içi vida penetrasyonu, subakromial sıkışma, varus kollapsı ve osteonekroz ve sekonder ameliyat gereksinimi ön plandaki komplikasyonlardır.[16,17] 382

Şekil 1. Kırk iki yaşında erkek hasta araç içi trafik kazası sonrası tip 4 kırık nedeniyle fiksasyon uygulandı. Ameliyatının üçüncü ayında varus açılanmasının görüntüsü.

Ulus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

Çelik ve ark. Proksimal humerus çok parçalı kırıklarında plak osteosentez ve hemiartroplasti sonuçları

tüberkülün yakınında yaklaşık 30 mm genişliğindeki avasküler bölgedir. Anatomik plak proksimali bu bölgeye yerleştirildiğinde, hem anterior humeral sirkumfleks arterin çıkan dalı, hem posterior sirkumfleks arterin posterior dalı korunabilmektedir. Plak fiksasyonu uyguladığımız 35 hastanın avasküler nekroz gelişen iki (%5.7) kişi hariç diğerlerinde osteonekroz bulgusu olmaksızın kaynama elde edildi. Bu iki hastada ameliyat öncesi yüksek enerjili travma sonucu oluşmuş neer tip 4 proksimal humerus kırık nedeniyle cerrahi uygulanmıştı. Her iki olguya da ikincil girişim olarak hemiartroplasti uygulandı. Proksimal humerus üç parçalı kırıklarda fiksasyon ile iyi sonuçlar elde edilebilirken dört parçalı kırıklarda kötü fonksiyonel sonuç olasılığı yüksektir.[21] Çalışmamızda literatürle uyumlu olarak üç parçalı kırıklarda fiksasyon ile daha başarılı sonuçlar elde ettik (Tablo 2 ve 3). Proksimal humerus kırıklarının cerrahi tedavisinde protez uygulanması birçok hekim tarafından kabul edilmiş bir yöntemdir. Kırıklı çıkık, şiddetli osteopeninin eşlik ettiği üç parçalı kırık, dört parçalı kırık, kollum anatomikum kırıklarında, humerus başının %50’sinden fazlasını ilgilendiren kompresyon kırıklarında ve başarısız fiksasyon sonrasında hemiartroplasti önerilen bir tedavi şeklidir.[6,19,22,23] Proksimal humerus kırığı nedeniyle uygulanan omuz artroplastisi ağrıyı gidermede başarılı olsa da, fonksiyonel sonuçları sınırlı kalmaktadır.[7,19,24] Tüberküllerin de kırık olduğu çok parçalı osteoporotik kırıklarda, protezin uygun pozisyonda ve yükseklikte stabil olarak yerleştirilmesi, tüberkül stabilitesinin sağlanması ve rotator manşetin tamiri güç olabilir. Bu zorluklar protezin fonksiyonel başarısını etkileyen faktörlerdir.[25,26] Tüm bunlarla birlikte hastanın yaşı, cinsiyeti, ameliyat olana kadar geçen süre, rehabilitasyon zamanı fonksiyonel sonuçları etkileyen diğer önemli etkenlerdir.[27,28,29] Yüzeyel ya da derin enfeksiyon, dislokasyon, gevşeme, refleks sempatik distrofi, subakromial sıkışma, periprostetik kırık, tuberculum majus deplasmanına sekonder rotator cuff disfonksiyonu, heterotopik ossifikasyon ve aksiller sinir yaralanması hemiartroplastinin olası komplikasyonlarıdır.[21,24,26,30] Hemiartroplasti uyguladığımız 23 hastanın dokuzunda (%39.1) fizik muayenede rotator cuff yetmezliği saptadık. Bu hastaları geriye dönük gözden geçirdiğimizde sadece biri hariç tümü tip 4 kırıktı ve ikisi hariç yedisinde düşük enerjili travma sonrası kırık oluşmuştu. Parsiyel protezde fonksiyonel olarak başarısız sonuç almamızın rotator cuff yetmezliği ile ilişkili olabileceğini düşünmekteyiz (Şekil 2). Literatürde proksimal humerus parçalı kırıklarında kilitli plak fiksasyonu ile hemiartroplasti uygulamasını karşılaştıran sınırlı sayıda çalışma mevcuttur. Kilitli plak uygulamasında daha iyi fonksiyonel sonuçlar elde edildiğini bildiren çalışmaların[31,32] yanı sıra deplase dört parçalı kırıklarda hemiartroplasti ile daha iyi sonuçlar elde edildiğini bildiren bir çalışma da mevcutUlus Travma Acil Cerrahi Derg, Haziran 2016, Cilt. 22, Sayı. 4

Şekil 2. Yetmiş sekiz yaşında kadın hastaya düşme sonrası tip 4 kırık nedeniyle hemiartroplasti uygulandı.Tüberkülüm majusun uygun fikse edilmemesine bağlı rotator cuff yetmezliği görüntüsü.

tur.[6] Dietrich ve ark.nın çalışmasında her iki cerrahi yöntemde yaş, cinsiyet ve kırık tipi ile fonksiyonel sonuçlar arasında ilişki tespit edilmemişken fiksasyon grubunda yüksek oranda revizyon cerrahisi (%25) gerekmiştir.[31] Proksimal humerus kırıklarında cerrahi süre ile ilgili optimal zaman tartışmalı olmakla birlikte erken dönemde uygulanan cerrahilerde başarı şansı yüksektir.[21,26,29] Çalışmamızda cerrahi süre bakımından her iki grup arasında istatistiksel olarak anlamlı farklılık tespit edilmiş olmasına rağmen, sürenin fonksiyonel sonuçlara anlamlı etkisi tespit edilememiştir. Ameliyat öncesi sürenin nispeten uzun olmasına hastaların ek problemler nedeniyle yapılan konsültasyonlar neticesinde başlanan tedavilerin ve malzeme temininde yaşadığımız problemlerin neden olduğunu belirledik. Proksimal humerus kırıklarında erken omuz eklem hareketlerine başlanması fonksiyonel durumun geri kazanılması açısından çok önemlidir. T.majus üzerindeki stresi azaltmak için ameliyat sonrası kol nötral ya da hafif eksternal rotasyonda sabitlenir. Genellikle ameliyat sonrası birinci günde pandüler hareket başlanır. Pasif ROM egzersizi başlatmak için karar hasta için bireysel olmalıdır ve cerrahın T.majusun fiksasyon gücüne güvenine bağlıdır. T.majus üzerindeki stresi azaltmak için iki-üç hafta ertelenebilir. Bununla birlikte dirsek ve el bileğinin nazik aktif eklem hareketleri ameliyat sonrası hemen başlanılmalıdır. Aktif 383

Çelik ve ark. Proksimal humerus çok parçalı kırıklarında plak osteosentez ve hemiartroplasti sonuçları

öne fleksiyon ve dış rotasyon egzersizleri T.majusun kaynaması radyografik olarak ortaya konana kadar geciktirilmelidir. Bu yaklaşık altı-sekiz haftayı bulmaktadır. Maksimum seviyede iyileşme ameliyat sonrası 9–12 ayı bulabilmektedir.[11] Sonuç olarak; çok parçalı proksimal humerus kırıklarının tedavisinde komplikasyon oranlarının yüksek oluşu göz önünde bulundurulmalıdır. Çalışmamızda en yüksek komplikasyon oranı olan rotator cuff yetmezliği için ameliyat esnasında rotator manşetin durumu tespit edilerek uygun tamir ve ameliyat sonrası yakın takip ile bu komplikasyon oranı düşürülüp tedavi başarısı artırılabilir düşüncesindeyiz.

Kısıtlılıklar Çalışmanın zayıf tarafı geriye dönük incelemenin olması ve hasta sayısının nispeten az oluşudur. Çıkar örtüşmesi: Bildirilmedi.

KAYNAKLAR 1. Lind T, Krøner K, Jensen J. The epidemiology of fractures of the proximal humerus. Arch Orthop Trauma Surg 1989;108:285–7. 2. Rose SH, Melton LJ 3rd, Morrey BF, Ilstrup DM, Riggs BL. Epidemiologic features of humeral fractures. Clin Orthop Relat Res 1982;168:24– 30. 3. Flatow EL. Fractures of the proximal humerus. In: Bucholz RW, Heckman JD, editors. Rockwood and Green’s fractures in adults. Vol. 1, 5th ed. Philadelphia: Lippincott Williams &Wilkins; 2001. p. 997–1041. 4. Kannus P, Palvanen M, Niemi S, Parkkari J, Järvinen M, Vuori I. Osteoporotic fractures of the proximal humerus in elderly Finnish persons: sharp increase in 1970-1998 and alarming projections for the new millennium. Acta Orthop Scand 2000;71:465–70. 5. Egol KA, Ong CC, Walsh M, Jazrawi LM, Tejwani NC, Zuckerman JD. Early complications in proximal humerus fractures (OTA Types 11) treated with locked plates. J Orthop Trauma 2008;22:159–64. 6. Neer CS 2nd. Displaced proximal humeral fractures. I. Classification and evaluation. J Bone Joint Surg Am 1970;52:1077–89. 7. Robinson CM, Murray IR. The extended deltoid-splitting approach to the proximal humerus: variations and extensions. J Bone Joint Surg Br 2011;93:387–92. 8. Constant CR, Murley AH. A clinical method of functional assessment of the shoulder. Clin Orthop Relat Res 1987;214:160–4. 9. Iannotti JP, Ramsey ML, Williams GR Jr, Warner JJ. Nonprosthetic management of proximal humeral fractures. Instr Course Lect 2004;53:403– 16. 10. Vachtsevanos L, Hayden L, Desai AS, Dramis A. Management of proximal humerus fractures in adults. World J Orthop 2014;5:685–93. 11. Cadet ER, Ahmad CS. Hemiarthroplasty for three- and four-part proximal humerus fractures. J Am Acad Orthop Surg 2012;20:17–27. 12. Aksu N, Göğüş A, Kara AN, Işiklar ZU. Complications encountered in proximal humerus fractures treated with locking plate fixation. Acta Orthop Traumatol Turc 2010;44:89–96. 13. Zhaojun S, Yongjie Y, Bin L, Bo Y, Ning M, Juan L. PHILOS plate fixation in proximal humeral fractures: functional outcomes. Life Science Journal 2013;10:3363–7. 14. Gardner MJ, Voos JE, Wanich T, Helfet DL, Lorich DG. Vascular im-

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plications of minimally invasive plating of proximal humerus fractures. J Orthop Trauma 2006;20:602–7. 15. Strohm PC, Helwig P, Konrad G, Südkamp NP. Locking plates in proximal humerus fractures. Acta Chir Orthop Traumatol Cech 2007;74:410–5. 16. Avcı CC, Gülabi D, Sağlam N, Kurtulmuş T, Saka G. Measurement of screw length through drilling technique in osteosynthesis of the proximal humerus fractures. Eklem Hastalik Cerrahisi 2013;24:156–62. 17. Owsley KC, Gorczyca JT. Fracture displacement and screw cutout after open reduction and locked plate fixation of proximal humeral fractures [corrected]. J Bone Joint Surg Am 2008;90:233–40. 18. Ong CC, Kwon YW, Walsh M, Davidovitch R, Zuckerman JD, Egol KA. Outcomes of open reduction and internal fixation of proximal humerus fractures managed with locking plates. Am J Orthop (Belle Mead NJ) 2012;41:407–12. 19. Gardner MJ, Weil Y, Barker JU, Kelly BT, Helfet DL, Lorich DG. The importance of medial support in locked plating of proximal humerus fractures. J Orthop Trauma 2007;21:185–91. 20. Kiliç B, Uysal M, Cinar BM, Ozkoç G, Demirörs H, Akpinar S. Early results of treatment of proximal humerus fractures with the PHILOS locking plate. [Article in Turkish] Acta Orthop Traumatol Turc 2008;42:149–53. 21. Min W, Davidovitch RI, Tejwani NC. Three-and four-part proximal humerus fractures: evolution to operative care. Bull NYU Hosp Jt Dis 2012;70:25–34. 22. Grönhagen CM, Abbaszadegan H, Révay SA, Adolphson PY. Mediumterm results after primary hemiarthroplasty for comminute proximal humerus fractures: a study of 46 patients followed up for an average of 4.4 years. J Shoulder Elbow Surg 2007;16:766–73. 23. Ozkayın N, Aktuglu K. Yaşlı hastalardaki dört parça proksimal humerus kırıklarının hemiartroplasti ile tedavisi. Eklem Hastalık Cerrahisi 2008;19:101–5. 24. Kontakis G, Koutras C, Tosounidis T, Giannoudis P. Early management of proximal humeral fractures with hemiarthroplasty: a systematic review. J Bone Joint Surg Br 2008;90:1407–13. 25. Aaron D, Parsons BO, Sirveaux F, Flatow EL. Proximal humeral fractures: prosthetic replacement. Instr Course Lect 2013;62:155–62. 26. Demirhan M. Factors affecting the results of hemiarthroplasty for proximal humerus fractures. Acta Orthop Traumato lTurc 2000;34:463–74. 27. Esen E, Doğramaci Y, Gültekin S, Deveci MA, Suluova F, Kanatli U, et al. Factors affecting results of patients with humeral proximal end fractures undergoing primary hemiarthroplasty: a retrospective study in 42 patients. Injury 2009;40:1336–41. 28. Reuther F, Müller S, Wahl D. Management of humeral head fractures with a trauma shoulder prosthesis: correlation between joint function and healing of the tuberosities. Acta Orthop Belg 2007;73:179–87. 29. Babhulkar A, Shyam AK, Sancheti PK, Shah K, Rocha S. Hemiarthroplasty for comminuted proximal humeral fractures. J Orthop Surg (Hong Kong) 2011;19:194–9. 30. Murray IR, Amin AK, White TO, Robinson CM. Proximal humeral fractures: current concepts in classification, treatment and outcomes. J Bone Joint Surg Br 2011;93:1–11. 31. Dietrich M, Meier C, Lattmann T, Zingg U, Grüninger P, Platz A. Complex fracture of the proximal humerus in the elderly. Locking plate osteosynthesis vs hemiarthroplasty. [Article in German] Chirurg 2008;79:231–40. [Abstract] 32. Solberg BD, Moon CN, Franco DP, Paiement GD. Surgical treatment of three and four-part proximal humeral fractures. J Bone Joint Surg Am 2009;91:1689–97.

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Çelik ve ark. Proksimal humerus çok parçalı kırıklarında plak osteosentez ve hemiartroplasti sonuçları

ORIGINAL ARTICLE - ABSTRACT OLGU SUNUMU

Mid-term follow-up evaluation of plate osteosynthesis and hemiarthroplasty results in multipart fractures of the proximal humerus Cem Çelik, M.D.,1 Seyit Ali Gümüştaş, M.D.,2 Gültekin Sıtkı Çeçen, M.D.,3 Güven Bulut, M.D.,3 Halil İbrahim Bekler, M.D.3 1 2 3

Department of Orthopaedic and Traumatology, Geyve State Hospital, Sakarya-Turkey Department of Orthopaedic and Traumatology, Yavuz Selim Bone Disease and Rehabilitation Hospital, Trabzon-Turkey Department of Orthopaedic and Traumatology, Kartal Dr. Lütfi Kirdar Training and Research Hospital, İstanbul-Turkey

BACKGROUND: The present objective was to retrospectively evaluate factors affecting functional outcome of multipart proximal humeral fracture treated with fixation or hemiarthroplasty. METHODS: Included were 58 patients (19 women, 39 men; average age: 51.04 years; range 22–78 years) who underwent surgery for Neer type III or IV proximal humeral fractures between 2007 and 2012. All participants attended follow-up of at least 2 years. A total of 35 patients underwent open reduction and anatomical plate fixation; 23 underwent partial shoulder replacement. Patients were evaluated according to Constant-Murley shoulder scoring at final follow-up examination. Evaluated impacts on functional outcome included age, gender, American Society of Anesthesiologists (ASA) Physical Status classification, trauma energy, type of fracture, and time to surgery. RESULTS: Mean follow-up duration was 47.25±13.29 (25–76) months. Mean Constant-Murley score was 58.65±18.62 (65.77±18.67 for the fixation group, 47.82±12.52 for the hemiarthroplasty group; p=0.001). When impact of independent variables on functional scores was assessed, ASA score and type of fracture were found to significantly affect functional outcome in the fixation group, and trauma energy was found to significantly affect functional outcome in the hemiarthroplasty group. Complications were detected in 20 patients (34.5%) upon final examination, 14 of whom (70%) had rotator cuff deficiency. DISCUSSION: Though improved functional results may be obtained using plate fixation in the surgical treatment of multipart proximal humeral fractures, the high rates of rotator cuff failure associated with both surgical methods should be considered. Keywords: Comminuted fractures; outcome assessment; proximal humerus; surgery. Ulus Travma Acil Cerrahi Derg 2016;22(4):379–385

doi: 10.5505/tjtes.2016.90402

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ORİJİ N A L Ç A LI Ş M A

Erişkin humerus alt uç eklem içi parçalı kırıklarda 90° ve 180° plak uygulamalarının karşılaştırılması ve klinik sonuçlar üzerine etkisi Dr. Volkan Eryuva,1 Dr. Taşkın Altay,2 Dr. Cemil Kayalı,2 Dr. Zafer Kement,2 Dr. Caner Çıtak2 1

Trabzon Fatih Devlet Hastanesi Ortopedi ve Travmatoloji Kliniği, Trabzon

İzmir Bozyaka Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İzmir

ÖZET AMAÇ: Bu çalışmanın amacı humerus alt uç eklemi ilgilendiren parçalı kırıklı hastalara uyguladığımız cerrahi tedavilerdeki 90° ve 180° açılı çift plak uygulamalarının sonuçları değerlendirilerek birbirlerine olan üstünlüklerini saptamaktır. GEREÇ VE YÖNTEM: Kliniğimizde 2009 Ocak ile 2013 Ocak tarihleri arasında AO sınıflandırmasına göre tip C erişkin distal humerus parçalı kırığı tanısıyla cerrahi tedavi uygulanan, en az 6 ay izleme süresi olan 17 hasta, geriye dönük olarak değerlendirildi. Hastaların poliklinik kontrollerinde ön-arka ve yan grafiler ile radyolojik değerlendirmeleri ve Mayo Dirsek Performans Skorlama sistemi kullanılarak dirsek işlevleri gözden geçirildi. BULGULAR: Olguların 14’ü (%82.3) erkek, üçü (%17.7) kadın olup yaş ortalaması (22–65) 40.5 yıl idi. AO/ASIF humerus distal uç kırık sınıflandırmasına göre; kırıkların üçü (%17.7) tip C1, dokuzu (%52.9) tip C2, beşi (%29.4) tip C3 kırık şeklindeydi. Bu kırıkların altısı (%35.3) açık olup, bunlarda Gustillo-Anderson’a göre dördü (%23.5) tip 1, ikisi (%11.7) tip 2 idi. Onbir hastada (%64.7) 90°, altı hastada ise (%36.3) 180° açılarla çift plak kullanıldı. Tüm hastalara chevron osteotomisi uygulandı. Hastalar ortalama (6–52) 25.6 ay takip edildi. Hastalarımızın en son kontrollerinde yapılan değerlendirmelerinde ortalama dirsek fleksiyonunun 105º (dağılım 85º–130º), ortalama ekstansiyon kaybının 10º (dağılım 0º–20º) olduğu saptandı. Mayo dirsek performans skorlama sistemine göre; 12 (%70.5) çok iyi, beş (%29.5) iyi sonuç elde edildiği görüldü. Doksan ve 180 derece plak yerleştirilen olguların klinik sonuçları arasında istatistiksel fark saptanmadı (p=0.169). SONUÇ: Erişkin distal humerus C tipi kırıklarda plakların hangi açılarla yerleştirileceğine ameliyat öncesi dönemde çekilen grafiler ve operasyon sırasında cerrahın seçimi neticesinde karar verilmelidir. Özellikle lateral kolondaki parçalanmanın plakların hangi açıyla uygulanacağını belirtmesi açısından önemi vardır. Lateral kolonda parçalanma yoksa 90° açıyla uygulanan çift plak eğer parçalanma varsa 180° açıyla uygulanan plaklama sonuçlar açısından yeterli olmaktadır. Anahtar sözcükler: Çift plak yöntemi ile açık redüksiyon; humerus distal kırıkları; olekranon osteotomisi.

GİRİŞ Son 20 yıldır, dirsek anatomisi ile cerrahi yaklaşımların daha iyi anlaşılması ve küçük kırık fragmanlarının bile tespitine imkan tanıyan tespit materyallerinin kullanıma girmesiyle cerrahi tedavi literatürde artan sıklıkta önerilmektedir.[1–4] Sorumlu yazar: Dr. Taşkın Altay, Bahar Mahallesi, Saim Çıkrıkcı Caddesi, No: 59, 35170 Bozyaka, İzmir Tel: +90 232 - 250 50 50 E-posta: taskinaltay@yahoo.com Ulus Travma Acil Cerrahi Derg 2016;22(4):386–390 doi: 10.5505/tjtes.2016.18827 Telif hakkı 2016 TJTES

386

Erişkin distal humerus kırıklarının nadir görülmeleri ve bölgenin karmaşık anatomisi nedeniyle bu tip kırıkların tedavisinde kesin bir protokol geliştirilememiştir. Bu çalışmanın amacı humerus alt uç eklemi ilgilendiren parçalı kırıklı hastalara uyguladığımız cerrahi tedavilerdeki 90° ve 180° açılı çift plak uygulamalarının sonuçları değerlendirilerek birbirlerine olan üstünlüklerini saptamaktır.

GEREÇ VE YÖNTEM Kliniğimizde 2009 Ocak ile 2013 Ocak tarihleri arasında AO sınıflandırmasına göre tip C erişkin distal humerus parçalı kırığı tanısıyla cerrahi tedavi uygulanan, en az altı ay izleme süresi olan 17 hasta çalışmaya alındı. Hasta dosyaları geriye dönük incelenerek hastaların yaşı, cinsiyetleri, yaralanma şekli ve tarihi, kırığın AO/ASIF sınıflandırUlus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

Eryuva ve ark. Erişkin humerus alt uç eklem içi parçalı kırıklarda 90° ve 180° plak uygulamalarının karşılaştırılması

masına göre tipi, hastanın ek patolojileri, Gustillo-Anderson açık kırık sınıflamasına göre tipi, cerrahi öncesi geçen süre, kullanılan cerrahi yaklaşım ve teknik, kırık tespit yöntemi, ameliyat sonrası takipte neler yapıldığı, komplikasyonlar, rehabilitasyon şekilleri değerlendirildi. Hastaların poliklinik kontrollerinde ön-arka ve yan grafiler ile radyolojik değerlendirmeleri ve Mayo Dirsek Performans Skorlama sistemi kullanılarak dirsek işlevleri gözden geçirildi.[5] Hastaların hepsinde cerrahi girişim genel anestezi altında supin pozisyonda ve turnike kontrolünde, dirsek 90 derece fleksiyonda aynı cerrah tarafından yapıldı. Posterior insizyon sonrası ulnar sinir eksplorasyonu yapılarak olekranona Chevron osteotomisi uygulandı ve plak açılanması lateral duvarda ki parçalanmaya göre seçildi. Ameliyat sonrası dirsek hareketlerine ağrıyı tolere eder etmez başlanıldı. Dikişler alınması sonrası atel çıkarıldı. Hastaların poliklinik kontrollerinde ön-arka ve yan grafiler ile radyolojik değerlendirmeleri ve Mayo Dirsek Performans Skorlama sistemi kullanılarak dirsek işlevleri gözden geçirildi. Plak açısı ile kırık tipi, açık kırık tipi iki farklı plaklama yönteminin istatiksel ilişkisi incelendi (Tablo 1). Plak açısı ile kırık tipi, açık kırık tipi ve mayo klinik sonuçları arasında istatistiksel olarak anlamlı bir farklılık olmadığı gözlendi (Tablo 2). Verilerin istatistiksel analizinde SPSS (SPSS Inc., Chicago, Illinois USA) 18.0 paket programı kullanılmıştır. Kategorik veri gruplarının karşılaştırılmalarında Pearson Ki-Kare testi kullanılmıştır.

BULGULAR Kliniğimizde, 2009 Ocak ile 2013 Ocak tarihleri arasında humerus alt uç eklemi ilgilendiren parçalı kırık tanısıyla tedavi edilen 17 hastanın 14’ü (%82.3) erkek, üçü (%17.7) kadın olup hastaların yaş ortalaması 40.5 (22–65) yıl idi. Kırıklarının nedenleri; 10 (%58.8) kırıkta basit düşme, dört (%23.5) kırıkta yüksekten düşme, üç (%17.7) kırıkta trafik kazası olarak saptandı. AO/ASIF humerus distal uç kırık sınıflandırmasına göre; kırıkların üçü (%17.7) tip C1, dokuzu (%52.9) tip C2, beşi (%29.4) tip C3 kırık şeklinde değerlendirildi. Hastalar travmadan ortalama 5.4 gün (2–9 gün) sonra ameliyat edildiler. Çalışmaya alınan 17 kırığın; 11’inde (%64.7) 90° açılı çift plak, altısında (%35.3) paralel kilitli çift plak ile osteosentez yapıldı. Hastalar ortalama 4.5 günde (2–9 gün) taburcu edildi. Dirsek hareketlerine ortalama 4.2 günde (3–8 gün) başlandı. Hastalarımızın izlenme süreleri en az altı ay, en fazla 52 ay, ortalama 25.6 ay idi. Ameliyat sonrası erken dönemde iki (%11.7) hastada geçici yüzeysel cerrahi alan enfeksiyonu görüldü. Bir (%5.8) hastada geçici ulnar sinir sorunu görüldü. Geç dönemde ise iki (%11.7) hastada heterotrofik ossifikasyon görüldü. Hastalarımızın en Ulus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

Tablo 1. Plak açısı ile kırık tipi, açık kırık tipi iki farklı plaklama yönteminin istatiksel ilişkisi Plak açısı

90°

180°

n % n %

Kırık tipi C1

5.8

11.6

7 41.1 2 11.6

3 17.6 2 11.6 p=0.365

Açık kırık Tip 1 2 11.6 2 11.6

Tip 2

11.6

Tip 3 0 0 0 0 p=0.478

Tablo 2. Mayo klinik sonuçları ile kırık tipi, açık kırık tipi, plak açısı, operasyon günü, yaş ve cinsiyet arasındaki istatistiksel ilişki Mayo

Kötü

Orta

İyi

Çok iyi

n (%)

Kırık tipi

2 (11.5)

1 (5.8)

2 (11.5)

7 (41.1)

1 (5.8)

4 (23.5)

=0.295

Açık kırık

Tip1

1 (5.8)

3 (17.6)

Tip 2

0 (0)

2 (5.8)

Tip 3

0 (0)

=0.569

Plak açısı

90°

2 (11.6)

8 (47)

180°

3 (17.6)

18–35

2 (11.6)

4 (23.5)

=0.169

Yaş

36–60

1 (5.8)

7 (41.1)

>60

1 (5.8)

=0.713

Cinsiyet

Kadın

1 (5.8)

2 (11.6)

Erkek

4 (23.5)

10 (58.8)

=0.870

son kontrollerinde yapılan değerlendirmelerinde ortalama dirsek fleksiyonunun 105º (dağılım 85º–130º), ortalama ekstansiyon kaybının 10º (dağılım 0º–20º) olduğu saptandı. Onyedi kırık Mayo dirsek performans skorlama sistemine göre değerlendirildiğinde; 12 (%70.5) çok iyi, beş (%29.5) iyi sonuç elde edildiği görüldü. Mayo klinik sonuçları ile kırık tipi, açık kırık tipi, plak açısı, operasyon günü, yaş ve cinsiyet arasındaki istatistiksel ilişki 387

Eryuva ve ark. Erişkin humerus alt uç eklem içi parçalı kırıklarda 90° ve 180° plak uygulamalarının karşılaştırılması

(a)

(b)

(d)

(e)

(f)

(g)

(c)

(h)

Figure 1. Ameliyat öncesi (a) ön arka ve (b) yan grafi. Ameliyat sonrası 38. ay 180° açı ile uygulanmış çift plak tespitinin (c) ön arka ve (d) yan grafisi. Ameliyat öncesi (e) ön arka ve (f) yan grafisi. Ameliyat sonrası 48. ay 90° açı ile uygulanmış çift plak tespitinin (g) ön arka ve (h) yan grafisi.

Tablo 2’de görüldüğü gibi istatistiksel olarak incelendi. Mayo klinik sonuçları ile kırık tipi, açık kırık tipi, plak açısı, yaş ve cinsiyet arasında istatistiksel olarak anlamlı bir farklılık olmadığı gözlendi.

TARTIŞMA Humerus alt uç eklemi içeren parçalı kırıkları tedavisi zor olan kırıklardır. Kırık sonrası tatmin edici ve ağrısız dirsek işlevinin sağlanması, eklem yüzeyinin anatomik restorasyonu ve kırık parçalarının stabil tespiti, aynı zamanda erken eklem hareketine başlanması ile olasıdır. Distal humerus kırıkları arasında eklemi ilgilendiren Tip C kırıklar en sorunlu grubu oluşturmaktadır. Tip C kırıklarda öncelikli önerilen tedavi cerrahidir. Kırık kompleks hale geldikçe fonksiyonel sonuçların kötüleştiği bildirilmiştir.[6–8] Çift plak uygulamalarında plakların pozisyonuyla ilgili tartışmalar devam etmektedir. Bu açıdan, O’Driscoll parçalanmanın fazla olduğu, kemik kalitesinin kötü olduğu karmaşık kırıklarda sagital planda paralel 2 plak (medial ve lateral) kullanılmasını ve 2.7 mm vidalar ile birbirini kilitleyecek tarzda, eklemi ilgilendiren parçalara daha fazla sayıda vida gönderilerek tespit yapılmasını önermektedir. Parçalanması olmayan ve kemik kalitesi iyi olan kırıklarda, klasik 90° açılı plak uygulaması ile sagital planda paralel iki plak uygulamasının aynı güvenilirlik388

te olduğunu söylemiştir.[9,10] Kendi çalışmamızda 90° açılı plak tespitini lateral kolonun parçalı olmadığı olgularda uyguladık. Medial kolonda ki parçalanma göz önünde bulundurmadık. Shin ve ark. klinik yaklaşımlarda paralel plaklamanın çok iyi kaynama ve rijit tespit sağlamasına rağmen, 90° açılı plak kullanımın da klinik sonuçlar ve komplikasyonlar açısından önemli bir fark oluşturmadığını gösterdiler. Anatomik redüksiyonun önemini vurguladılar.[11] Lee ve ark. kendi pratiklerinde her iki plaklama tekniği ile yapılan ameliyatlarda hem klinik sonuçları hem de komplikasyon oranları arasında önemli fark bulmadılar.[12] Benzer olarak bizim çalışmamızda her iki plaklama yöntemiyle klinik ve radyolojik olarak birbirine yakın sonuçlar elde ettik. Anatomik ve stabil redüksiyonun kırık iyileşmesinde önemli olduğu görüşüne katılıyoruz. Klinik çalışmaların görece daha az olmasına rağmen daha fazla sayıda biyomekanik çalışmalar literatürde vardır. Ancak biyomekanik çalışmalarda klinik uygulamaların fonksiyonel ve radyolojik sonuçlarının in vitro çalışmalarla uyumlu olmayabileceği vurgulanmıştır. Klinik çalışmalar her iki plaklamanın eşit sonuçlar meydana getirdiğini belirtmesine rağmen Got ve ark.nın biyomekanik çalışmalarında 180° açıyla uygulanan plaklamanın parçalı humerus distal kırıklarında torsiyonel güçlere daha fazla direnç gösterdiğini tespit ettiler.[13] Ulus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

Eryuva ve ark. Erişkin humerus alt uç eklem içi parçalı kırıklarda 90° ve 180° plak uygulamalarının karşılaştırılması

Schwartz ve ark., her iki sistemin benzer kırık tespitinde teorik olarak benzer mekanik dayanıklılık sağladığını gösterdiler. Plak yük binmesinde ki farklılıkların kırık parçalarının pozisyonu ile ilgili olduğunu fakat plak yük binmesinde ki etkinin in vivo olarak belirsiz olduğunu vurguladılar.[14] Caravaggi ve ark. biyomekanik çalışmalarında ortogonal kilitli ve kilitsiz plaklarla paralel uygulanan kilitli plakları karşılaştırdıklarında paralel kilitli plakların oldukça yüksek oranda aksiyel yük uygulamasında ve son yetmezlik gücünde anlamlı fark gösterdiler. Her ne kadar biyomekanik olarak paralel plaklar üstün gözükse de; kırığın etrafında ki yumuşak doku ve cerrahi işlem göz önüne alındığında bu üstünlüğün klinik olarak kanıtlanmasının zor olacağını vurgulamışlardır.[15] Biyomekanik çalışmalarda 180° açılı plaklamanın daha rijit tespit yaptığı bulunmasına rağmen klinik çalışmalar da her iki plaklamanın rijit fiksasyon sağladığı görülmüştür. Bu farklılığı hastaların ameliyat sonrası ekstremitelerini daha koruyucu olarak kullanmaları ve kaynama sağlandıktan sonra normal yaşamlarına geçmeleri olarak açıklanabilir. Biyomekanik çalışmalarda kırığın iyileşme faktörleri göz önünde bulundurulmamıştır. Çalışmamızda olgularda plak yerleşiminde ve plakların birbirleriyle 90° veya 180° açıyla yerleştirilmesine operasyon öncesi çekilen grafilere göre ve operasyon sırasındaki direkt bakı sonucunda olguyu yapan cerrahın kendi deneyimine göre yerleştirmesini sağladık. Altı hastada 180° anatomik kilitli plak-vida sistemi ve 11 hastada 90° açılı plak kullanıldı. Bu 17 olguda %100 oranında çok iyi ve iyi sonuç elde edildi. Her iki plaklama yönteminin arasında klinik çalışmamızda bir fark görülmedi. Rehabilitasyon sonuçların başarısını etkileyen en önemli basamaktır. Başarılı sonuçları olan çalışılmaların tümünde erken rehabilitasyon üzerinde önemle durulmaktadır.[6,7,16] Ameliyat sonrası ikinci günden itibaren eklem hareketine başlanan çalışmalar vardır.[17,18] Çalışmamızdaki olgularda immobilizasyon, yapılan internal tespitin stabilitesi ve kırık parçalılığı dikkate alınarak yapıldı. Bu süre ortalama 4.2 gün idi. Elde edilen mayo klinik sonuçlara bakıldığında tüm hastalarda çok iyi ve iyi sonuç elde etmemizi sıkı tespit sonrası erken hareket vermeye bağlı olabileceğini düşünüyoruz. Humerus distal uç eklemi ilgilendiren kırıkların cerrahi tedavisi sonrası literatürdeki fonksiyonel sonuçlara bakıldığında; Kaushal ve arkadaşları bu tip olguların %77’sinde başarılı sonuç elde ettiklerini bildirmişlerdir.[19] Papaioannou ve ark. AO tip C kırıklı 75 olguluk çalışmalarında, minimal osteosentez uyguladıkları 21 olgunun %38’inde, sıkı internal tespit uyguladıkları 54 olgunun %77.8’inde çok iyi ve iyi sonuç bildirmişlerdir.[20] John ve ark. 75 yaş ve üzeri 49 hastanın %80’inde çok iyi ve iyi sonuç almışlardır.[21] Çalışmamızda tip C kırıklı 17 hastanın 17 kırığı genel olarak değerlendirildiğinde %100 çok iyi ve iyi sonuç elde edildi. Sonuçlarımız literatürle uyumlu idi. Stabil tespit yapılan olgularda erken hareket verilebilmesinin başarıyı artırdığını düşünüyoruz. Ulus Travma Acil Cerrahi Derg, Temmuz 2016, Cilt. 22, Sayı. 4

Plaklama yöntemleri için daha net sonuçlar elde etmek için daha çok sayıda olguya ve uzun süreli takiplere gereksinim olabilir. Ancak bu çalışmanın meta analizlere yönelik faydaları olacağı düşünülebilir.

Sonuç Erişkin distal humerus C tipi kırıklarda plakların hangi açılarla yerleştirileceği amileyat öncesi dönemde çekilen grafiler, operasyon sırasında cerrahın seçimi neticesinde karar verilmelidir. Özellikle lateral kolondaki parçalanmanın plakların hangi açıyla uygulanacağını belirtmesi açısından önemi vardır. Lateral kolonda parçalanma yoksa 90° açıyla uygulanan çift plak eğer parçalanma varsa 180° açıyla uygulanan plaklama sonuçlar açısından yeterli olmaktadır. Çıkar örtüşmesi: Bildirilmedi.

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ORIGINAL ARTICLE - ABSTRACT OLGU SUNUMU

Comparison of 90° and 180° plate constructions for comminuted distal humerus fractures in adults, and effects on clinical results Volkan Eryuva, M.D.,1 Taşkın Altay, M.D.,2 Cemil Kayalı, M.D.,2 Zafer Kement, M.D.,2 Caner Çıtak, M.D.2 1 2

Department of Orthopaedics and Traumatology, Trabzon Fatih State Hospital, Trabzon-Turkey Department of Orthopaedics and Traumatology, İzmir Bozyaka Training and Research Hospital, İzmir-Turkey

BACKGROUND: The present objective was to compare 90° and 180° double-plate constructions for complex distal humerus fractures, as well as to evaluate superiority of construction type. METHODS: Retrospectively evaluated were 17 patients treated for type C distal humerus fracture according to AO/ASIF classification between January 2009 and January 2013. All attended minimum 6-month follow-up. Elbow function was assessed with anteroposterior and lateral x-ray, and Mayo elbow performance score evaluation at outpatient clinics. RESULTS: Patient population included 14 males (82.3%) and 3 females (17.7%). Mean patient age was 40.5 years. According to AO/ASIF distal humerus classification, 3 (17.7%) type C1, 9 (52.9%) type C2, and 5 (29.4%) type C3 fractures were included. Six were open fractures (35.3%). According to Gustilo-Anderson classification, 4 (23.5%) fractures were type 1, and 2 (11.7%) were type 2. Construction performed was 90° in 11 cases (64.7%) and 180° in 6 cases (36.3%). Chevron osteotomy was performed in all cases. Mean follow-up period was 25.6 (6–52) months. Upon final examination, mean elbow flexion was 105º (85º–130º), and mean extension loss was 10º (0º–20º). According to Mayo elbow performance scoring system, 12 (70.5%) results were excellent, and 5 (29.5%) were good. No statistically significant clinical difference was found between 90° and 180° plate construction groups (p=0.169). DISCUSSION: Surgeons should determine the construction type appropriate to individual cases of adult distal humerus type C fractures using preoperative x-rays and intraoperative means. Choice of construction type has particular importance in cases of lateral columnar fracture complexity. If no comminution is present in the lateral column, 90º double-plating leads to satisfactory outcome, while 180º plating leads to satisfactory outcome when comminution is present in the lateral column. Keywords: Distal humerus fractures; olecranon osteotomy; open reduction with double plating. Ulus Travma Acil Cerrahi Derg 2016;22(4):386–390

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Acute abdomen caused by greater omentum torsion: A case report and review of the literature Camilla Cremonini, M.D., Andrea Bertolucci, M.D., Dario Tartaglia, M.D., Francesca Menonna, M.D., Christian Galatioto, M.D., Massimo Chiarugi, M.D. Department of Emergency Surgery Unit, UniversitĂ Di Pisa, Pisa-Italy

ABSTRACT Torsion of the greater omentum is a rare cause of acute abdomen. Based on etiopathogenesis, it can be classified as primary or secondary. However, regardless of the cause, segmentary or diffuse omental necrosis will follow. Preoperative diagnosis is not easy, though abdominal ultrasound and computed tomography (CT) scans may show peculiar features suggestive of omental torsion. Laparoscopic resection of the affected omentum is the treatment of choice. Presently reported was a case of primary omental torsion, in addition to a comprehensive literature review. Keywords: Acute abdomen; greater omentum; laparoscopy; omental infarction; torsion.

INTRODUCTION Omental infarction is a rare cause of acute abdomen. The infarction is primarily caused by torsion of the greater omentum, and can be classified as primary, first described by Eitel in 1899, or as secondary to other diseases.[1] It mainly affects adults, occurring in men twice as frequently as in women, with the majority of those affected being overweight.[2] Preoperative diagnosis is difficult, as symptoms are unspecific and may easily be mistaken for those of other diseases, such as acute appendicitis, acute cholecystitis, or right-sided diverticulitis. [3,4] However, the increasing spread of high-quality imaging, particularly computed tomography (CT), has allowed for preoperative diagnosis to be performed much more often.[5] Presently described was a case of omental infarction caused by primary torsion. A review of the literature concerning this unusual cause of acute abdomen was also included.

CASE REPORT A 28-year-old male presented to the emergency department Address for correspondence: Camilla Cremonini, M.D. Via Vanni 4 56126 Pisa, Italy Tel: +39 340 86 50 416 E-mail: camilla.cremonini@outlook.com Qucik Response Code

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with a 4-day history of abdominal pain, mainly localized in the right quadrants, associated with anorexia. No nausea nor vomiting were present. The patient had no previous abdominal surgery in his medical history, but reported mild symptoms consistent with gastritis that had begun 4 months prior. The patient was hemodynamically stable and apyretic. The abdomen was soft, not distended, showing tenderness in the right iliac fossa and the right upper quadrant, with physical signs of peritoneal irritation. Laboratory investigation was normal, revealing no other abnormalities. Abdominal ultrasound showed a roundish hyperechoic lesion in correspondence with the right colon, in the absence of fluid effusion. Abdominal CT scan confirmed the presence of an oval thickening of fat tissue containing convoluted and twisted blood vessels in the right abdomen. These CT features raised suspicion of an area of omental infarction (Figure 1). Laparoscopy confirmed hemorrhagic infarction with necrosis of the section of the greater omentum attached to the proximal transverse colon; the remainder of the omentum appeared normal. A torsion point with occlusion of blood vessels tributary to the infarcted omentum was identified, and necrotic tissue was resected (Figure 2). No other concomitant intraperitoneal disease was identified. Course of treatment was unremarkable, and the patient was discharged on day 2 in healthy condition. 391

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(a)

(b)

Figure 1. Contrast-enhanced abdominal CT. (a, b) Local mass of fat density in a whirling pattern at the twisted point of the omentum (arrows).

(a)

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Figure 2. Intraoperative findings. (a) The right section of the greater omentum twisted twice in a clockwise direction (black arrow), and the infracted distal part of the omentum (white arrow). (b) Omental vessels twisted by torsion (arrow).

DISCUSSION Torsion of the greater omentum is an uncommon cause of acute abdomen, accounting for 1.1% of all cases of acute abdominal pain.[6] Omental torsion is difficult to diagnose preoperatively, and accurate preoperative diagnosis is reported in only 0.6–4.8% of cases.[7] When compared with appendicitis, this pathology has an incidence of 0.0016–0.37%, a ratio of less than 4 cases per 1000 cases of acute appendicitis. [8] Omental torsion is primarily seen in the 30–50-year age group, with male predominance.[1,9] However, a few cases have been reported in children.[10] Estimated incidence of primary omental torsion in children undergoing surgery for suspected appendicitis ranges between 0.024–0.1%.[9,11] Omental torsion is classified as primary or secondary, the latter being far more common.[8] Primary or idiopathic torsion is a rare condition, occurring in the absence of associated or secondary intraabdominal pathology.[1] Eitel first described 392

it, in 1899, as a rare surgical cause of acute abdomen. Thus far, approximately 300 cases have been reported. Pathogenesis of primary omental torsion is considered to be wideranging. Adams classified the pathogenesis of primary torsion into “predisposing factors” and “precipitating factors.”[12] Predisposing factors include obesity and anatomic variations in the arrangement of omental blood vessels. Obesity is a well-documented risk linked to primary torsion, with 1 study reporting that almost 70% of patients with omental infarction were obese.[13] Precipitating factors include trauma and acute changes in body position. Secondary torsion is more common and is associated with abdominal pathology, including inguinal hernia (the pathology most commonly associated), tumors in the omentum, cysts, intraabdominal inflammation, and post-surgical wound or scarring.[14] Adams,[12] and Barcia and Nelson[15] emphasized the association between right inguinal hernia and secondary omental torsion. Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

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No anatomic cause or pathology, such as obesity, adhesion, or hernia, could be determined in the present patient. A precipitating factor could be identified; the patient had sustained blunt abdominal trauma (multiple falls while skiing) only 24 hours prior to onset of symptoms. For these reasons, diagnosis of primary omental torsion was made. Pathophysiology of omental torsion involves rotation around the long axis, resulting in vascular compromise and impaired blood supply.[16] As the torsion progresses, arterial occlusion leads to acute hemorrhagic infarction, and eventually to necrosis of the omentum.[14] Spontaneous reduction of omental torsion has sporadically been reported.[17] In a large majority of reported cases, omental torsion with infarction was segmental, involving the right side of the omentum, as it is longer, heavier, and more mobile than the left side.[18–20] Clinical picture of primary and secondary omental torsion is similar. The earliest symptom associated with omental torsion is constant nonradiating pain of increasing severity, mostly localized in the right lower quadrant.[21] The majority of cases present with a single episode of abdominal pain, and recurrent pain may suggest intermittent torsions.[22] In addition, 50% of patients present with low-grade fever and moderate leukocytosis.[4] Gastrointestinal symptoms, such as nausea, anorexia, and vomiting, are uncommon.[5] Physical examination reveals signs of peritoneal irritation with guarding of rebound abdominal tenderness. If a large section of the omentum is involved, a mass may be palpable.[3] Omental torsion can mimic a variety of other acute abdominal conditions. Differential diagnosis should include acute appendicitis, cholecystitis, cecal diverticulitis, perforated duodenal ulcer, abdominal wall hematoma, and intestinal obstruction. [9,23] In women of reproductive age, salpingitis, ovarian cyst torsion, and ectopic pregnancy should also be considered. In children, differential diagnosis should also include inflammation of the Meckel’s diverticulum, as well as mesenteric adenitis.[9] Finally, torsion of accessory spleen is another diagnostic possibility, as an accessory spleen, when present, usually resides inside the omentum. Abdominal ultrasound is important in the exclusion of other acute conditions, and usually shows an ovoid or cake-like hyperechoic mass adherent to the peritoneum. CT scan can easily differentiate omental torsion from acute cholecystitis, appendicitis, and cecum diverticulitis. Classic signs of omental torsion on CT scan are hazy, but may include the whirl sign of a fatty mass with concentric linear strands in the greater omentum. Balthazar et al. showed that magnetic resonance imaging (MRI) was effective, even when omental torsion was complicated by bleeding or development of abscess.[24] However, because CT scan is the gold standard diagnostic modality in patients presenting with acute abdomen,[23] the need for MRI to establish a diagnosis of omental torsion is rare. Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Once diagnosed, omental torsion should be surgically managed. Surgical resection of the affected omentum, possibly achieved via laparoscopy, is the treatment of choice.[25,26] Surgery may also offer definitive diagnosis, if not established preoperatively. Advantages of laparoscopy include complete examination of the abdominal cavity to confirm diagnosis, in addition to the benefits of minimal-access surgery, which include decreased postoperative pain and wound-related complications.[27,28] Laparoscopy was presently successfully performed, without the need for open conversion. Alternative to surgery, conservative management of omental torsion has been proposed for patients who are hemodynamically stable.[5] In this event, oral analgesics, anti-inflammatory drugs, and prophylactic antibiotics are administered, though patient selection should include a careful imaging workup to exclude other acute abdominal pathologies.[29] Patients conservatively treated may require extended use of analgesia, and may suffer from other complications, such as abscess formation and adhesions induced by the persistence of necrotic tissue in the abdomen.[28,30,31] Regardless of these drawbacks, conservative management may succeed, particularly in patients with no associated complication.[32–34]

Conclusion Primary torsion of the omentum is a rare pathology, presenting as acute abdomen and mimicking acute appendicitis in a majority of cases. Preoperative diagnosis may be difficult, but can be achieved using diagnostic imaging, particularly CT scan. Laparoscopy could be considered as the first-hand surgical option, both for differential diagnosis and treatment. Conservative treatment may be offered as an option, though only after careful selection of patients. Conflict of interest: None declared.

REFERENCES 1. Y G, R A. Omental torsion. J Clin Diagn Res 2014;8:NE01–2. 2. Mavridis G, Livaditi E, Baltogiannis N, Vasiliadou E, ChristopoulosGeroulanos G. Primary omental torsion in children: ten-year experience. Pediatr Surg Int 2007;23:879–82. 3. Scabini S, Rimini E, Massobrio A, Romairone E, Linari C, Scordamaglia R, et al. Primary omental torsion: A case report. World J Gastrointest Surg 2011;3:153–5. 4. Breunung N, Strauss P. A diagnostic challenge: primary omental torsion and literature review - a case report. World J Emerg Surg 2009;4:40. 5. Kerem M, Bedirli A, Mentes BB, Sakrak O, Pala I, Oguz M. Torsion of the greater omentum: preoperative computed tomographic diagnosis and therapeutic laparoscopy. JSLS 2005;9:494–6. 6. Aronsky D, Z’graggen K, Banz M, Klaiber C. Abdominal fat tissue necrosis as a cause of acute abdominal pain. Laparoscopic diagnosis and therapy. Surg Endosc 1997;11:737–40. 7. Poujade O, Ghiles E, Senasli A. Primary torsion of the greater omentum: case report-review of literature: diagnosis cannot always be performed before surgery. Surg Laparosc Endosc Percutan Tech 2007;17:54–5. 8. Pinedo-Onofre JA, Guevara-Torres L. Omental torsion. An acute abdomen etiology. [Article in Spanish] Gac Med Mex 2007;143:17–20. [Abstract]

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Cremonini et al. Acute abdomen caused by greater omentum torsion 9. Tsironis A, Zikos N, Bali C, Pappas-Gogos G, Koulas S, Katsamakis N. Acute abdomen due to primary omental torsion: case report. J Emerg Med 2013;44:45–8. 10. Ozbey H, Salman T, Celik A. Primary torsion of the omentum in a 6-year-old boy: report of a case. Surg Today 1999;29:568–9. 11. Valioulis I, Tzallas D, Kallintzis N. Primary torsion of the greater omentum in children - a neglected cause of acute abdomen? Eur J Pediatr Surg 2003;13:341–3. 12. Adams JT. Primary torsion of the omentum. Am J Surg 1973;126:102– 5. 13. van Breda Vriesman AC, Lohle PN, Coerkamp EG, Puylaert JB. Infarction of omentum and epiploic appendage: diagnosis, epidemiology and natural history. Eur Radiol 1999;9:1886–92. 14. Borgaonkar V, Deshpande S, Rathod M, Khan I. Primary Omental Torsion Is a Diagnostic Challenge in Acute Abdomen-a Case Report and Literature Review. Indian J Surg 2013;75:255–7. 15. Barcia PJ, Nelson TG. Primary segmental infarction of the omentum with and without torsion. Am J Surg 1973;126:328–31. 16. Theriot JA, Sayat J, Franco S, Buchino JJ. Childhood obesity: a risk factor for omental torsion. Pediatrics 2003;112(6 Pt 1):460. 17. Saraç AM, Yeğen C, Aktan AO, Yalin R. Primary torsion of the omentum mimicking acute appendicitis: report of a case. Surg Today 1997;27:251– 3. 18. Puylaert JB. Right-sided segmental infarction of the omentum: clinical, US, and CT findings. Radiology 1992;185:169–72. 19. Ceuterick L, Baert AL, Marchal G, Kerremans R, Geboes K. CT diagnosis of primary torsion of greater omentum. J Comput Assist Tomogr 1987;11:1083–4. 20. Hirano Y, Oyama K, Nozawa H, Hara T, Nakada K, Hada M, et al. Left-sided omental torsion with inguinal hernia. World J Gastroenterol 2006;12:662–4. 21. López-Colombo A, Montiel-Jarquín A, García-Carrasco M, Nava A, Arcega-Domínguez A, Martínez-Fernández R, et al. Torsion of the omentum. A rare cause of acute abdomen. Rev Med Inst Mex Seguro Soc

2010;48:549–52. 22. Parr NJ, Crosbie RB. Intermittent omental torsion--an unusual cause of recurrent abdominal pain? Postgrad Med J 1989;65:114–5. 23. Naffaa LN, Shabb NS, Haddad MC. CT findings of omental torsion and infarction: case report and review of the literature. Clin Imaging 2003;27:116–8. 24. Balthazar EJ, Lefkowitz RA. Left-sided omental infarction with associated omental abscess: CT diagnosis. J Comput Assist Tomogr 1993;17:379–81. 25. Sánchez J, Rosado R, Ramírez D, Medina P, Mezquita S, Gallardo A. Torsion of the greater omentum: treatment by laparoscopy. Surg Laparosc Endosc Percutan Tech 2002;12:443–5. 26. Costi R, Cecchini S, Randone B, Violi V, Roncoroni L, Sarli L. Laparoscopic diagnosis and treatment of primary torsion of the greater omentum. Surg Laparosc Endosc Percutan Tech 2008;18:102–5. 27. Chung SC, Ng KW, Li AK. Laparoscopic resection for primary omental torsion. Aust N Z J Surg 1992;62:400–1. 28. Gassner PE, Cox MR, Cregan PC. Torsion of the omentum: diagnosis and resection at laparoscopy. Aust N Z J Surg. 1999;69:466–7. 29. Coulier B. Segmental omental infarction in childhood: a typical case diagnosed by CT allowing successful conservative treatment. Pediatr Radiol 2006;36:141–3. 30. Itenberg E, Mariadason J, Khersonsky J, Wallack M. Modern management of omental torsion and omental infarction: a surgeon’s perspective. J Surg Educ 2010;67:44–7. 31. Fragoso AC, Pereira JM, Estevão-Costa J. Nonoperative management of omental infarction: a case report in a child. J Pediatr Surg 2006;41:1777–9. 32. Kepertis C, Koutsoumis G. Primary torsion of the greater omentum. Indian Pediatr 2005;42:613–4. 33. Rimon A, Daneman A, Gerstle JT, Ratnapalan S. Omental infarction in children. J Pediatr 2009;155:427–31. 34. Soobrah R, Badran M, Smith SG. Conservative management of segmental infarction of the greater omentum: a case report and review of literature. Case Rep Med 2010.

OLGU SUNUMU - ÖZET

Omentum majus torsiyonunun neden olduğu akut batın: Olgu raporu ve literatürün gözden geçirilmesi Dr. Camilla Cremonini, Dr. Andrea Bertolucci, Dr. Dario Tartaglia, Dr. Francesca Menonna, Dr. Christian Galatioto, Dr. Massimo Chiarugi Di Pisa Üniversitesi, Acil Cerrahi Bölümü, Pisa-İtalya

Omentum majusun torsiyonu akut karının nadir bir nedenidir. Etiyopatogenezine dayanarak primer ve sekonder olarak sınıflandırılabilir. Ancak, sonuçta nedene bağlı olmaksızın segmenter veya yaygın omentum nekrozu oluşacaktır. Ameliyat öncesi tanı kolay olmamasına rağmen karının ultrason ve bilgisayarlı tomografi (BT) taramaları omentum torsiyonunu düşündüren özgün özellikleri gösterebilir. Seçilecek tedavi etkilenmiş omentumun laparoskopik rezeksiyonudur. Bu olgu sunumunda, kapsamlı literatür derlemesine ilaveten primer omentum torsiyonu bildirilmiştir. Anahtar sözcükler: Akut batın; laparoskopi; omentum enfarktı; omentum majus; torsiyon. Ulus Travma Acil Cerrahi Derg 2016;22(4):391–394

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Embolism of a pellet after shotgun injury: From liver to right ventricle Selim Bakan, M.D.,1 Bora Korkmazer, M.D.,1 Ahmet Baş, M.D.,1 Osman Şimşek, M.D.,2 Hasan Ali Barman, M.D.,3 Deniz Çebi Olgun, M.D.1 1

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

Department of General Surgery, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

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

ABSTRACT Bullet embolism to the heart is a rare but serious complication of penetrating trauma. Distant migration of foreign bodies via the vascular system must be taken into consideration following penetrating gunshot trauma. Delays in diagnosis may result in poor management and subsequent complications that may lead to grave prognosis. Presently described was a conservatively managed case of asymptomatic intracardiac pellet embolization. Highlighted was the importance of serial scanning for intravascular migration of pellet following penetrating gunshot injury, in addition to conservative management in asymptomatic patients. Keywords: Heart; pellet embolization; gunshot injury.

INTRODUCTION Bulllet embolism is a relatively rare but potentially life-threatening complication of penetrating missile injury. Bullets from penetrating wounds can access the vasculature and migrate to nearly every large vascular bed. Patients may be asymptomatic or present with devastating complications such as sepsis, ischemia, endocarditis, cardiac valvular incompetence, stroke, and pulmonary embolism.[1] Presently reported was a case of asymptomatic venous embolization, in which a pellet possibly migrated from the right hepatic vein to the interventricular septum. The case was managed conservatively after failure of endovascular methods due to arrhythmia.

CASE REPORT A previously healthy 29-year-old male was brought to the Address for correspondence: Selim Bakan, M.D. İstanbul Üniversitesi, Cerrahpaşa Tıp Fakültesi, Radyoloji Anabilim Dalı, Fatih, İstanbul Turkey Tel: +90 505 - 934 51 56 E-mail: dr.selim79@gmail.com Qucik Response Code

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emergency department with gunshot injuries. Physical examination revealed multiple millimetric hemorrhagic entrance holes in the anterior abdominal wall, anterior chest wall, bilateral thigh region, right suprapubic region, left supraorbital region and metacarpophalangeal joint of the third finger of the left hand. Glasgow Coma Scale score was 15. Upon arrival, the pulse was 98 bpm, with systolic blood pressure of 100 mmHg. Thoracoabdominal computed tomography (CT) was performed in order to evaluate the thoracoabdominal region, as well as pellet trajectory. Thorax CT revealed a metallic foreign body in the inferior lobe superior segment of the left lung, as well as in the sternum. Densities consistent with contusion were present in the superior lobe posterior segment, inferior lobe superior segment, and inferior lingular segment of the left lung. On abdominal CT, pellets were observed in the right lobe of the liver (segment 6), the posterior wall of the gastric corpus, the anterior perigastric fatty tissue, the jejunum, the bilateral perinephric tissues, the left psoas muscle, and the subcutaneous tissue of the abdominal wall. Lacerations were detected in the anterosuperior—posteroinferior aspects of the spleen, as well as in the posterolateral left kidney. Abdominal CT also revealed widespread high-density fluid within the abdomen. The patient was in hypovolemic shock one hour after arrival, and was emergently transferred to surgery for abdominal exploration, which revealed hemorrhagia from the spleen and 395

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retroperitoneal vessels in the peripancreatic region. After splenectomy provided better exposure, hematoma due to laceration of the pancreatic tail was detected. Regions of active bleeding were repaired with primary suturation. Due to the presence of focal hemorrhagic spots secondary to massive transfusion coagulopathy, Mikulicz tamponade was placed over the splenectomy lodge and distal pancreatic region. Intestinal edema was observed, and Bogota bag technique was performed to prevent abdominal compartment syndrome. Reoperation was planned for 24 hours later. Detected during the second operation were multiple entrance holes in the jejunum, as well as a few in the gastric corpus, the posterior wall of the gastric antrum, and the anterolateral wall of the caecum. Margins of the existing entrance holes were debrided and repaired with modified Gambee sutures. Surgery was concluded following control of bleeding and debridement of the necrotic entrance holes in the anterior abdominal wall. The patient survived, with a good clinical course. No complication was observed, though the majority of the pellets remained in the abdomen.

On the tenth postoperative day, abdominal CT (Fig. 1) showed a single pellet in the interventricular septum, with no indication of cardiac or mediastinal injury. Transthoracic 3-dimensional echocardiography (Fig. 2) confirmed the location of the pellet in the side of the interventricular septum facing the right ventricle, with no pericardial effusion or evidence of free-wall perforation. In order to investigate the source of the pellet embolization, prior (preoperative) and recent (postoperative day 10) thoracoabdominal CT examinations were compared (Fig. 3). The pellet was located in segment 6 of the liver on prior CT examination, but could not be detected on current CT scan. No other significant differences in location of the pellets remaining in the abdomen or thorax were observed upon comparison. The most plausible explanation for the intracardiac location of the pellet was determined as intravascular migration from the right hepatic vein to the heart via the inferior vena cava. The patient was taken to the interventional radiology unit for endovascular retrieval of the intracardiac pellet. Under local anesthesia following right axillary vein puncture with Seldinger technique, 5-F introducer placement was performed. Access to the right atrium and right ventricle was obtained through the right axillary vein and superior vena cava. Mul-

(a)

Figure 1. Axial CT scan showing a single pellet in the interventricular septum, with no suggestion of cardiac or mediastinal injury.

(b)

Figure 2. Transthoracic 3-dimensional echocardiography confirming location of the pellet (white arrow) in the side of the interventricular septum facing the right ventricle, 12 mm above the tricuspid annulus.

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Figure 3. (a) Preoperative axial CT scan showing the pellet located in segment 6 of the liver. (b) The pellet in the liver could not be detected on postoperative day 10 axial CT scan.

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(a)

(b)

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Figure 4. (a, b) Posteroanterior and lateral chest x-rays revealing the pellet (black arrows) in the silhouette of the heart, 6 weeks after discharge. (c) Echocardiograms at 6 months after discharge showing the pellet (white arrow) within the interventricular septum.

tiple attempts to remove the pellet with snare catheter failed because the foreign body was presumably embedded in the papillary muscles. Due to recurrent episodes of arrhythmia, the procedure was terminated. No further attempts were made, and conservative management was selected. Outpatient review with x-rays and echocardiograms at 6 weeks and 6 months following discharge demonstrated that the pellet remained within the interventricular septum (Fig. 4), presumably having become epithelialized.

DISCUSSION Exact incidence of bullet embolism in non-military circumstances is unclear, but may be increased due to use of lowkinetic-energy weapons in civilian settings.[1] Upon impact, the penetrating foreign body either pierces or is retained by tissues following loss of kinetic energy. It can enter the vessel directly at the time of injury or gradually erode into the lumen via the pulsating movement of the vessel against the foreign body.[2] Bullet embolization can be arterial or venous, with most documented cases being arterial.[3] Arterial embolization typically originates from the large arteries, left ventricle, aorta, or pulmonary veins, and often embolizes to lower-extremity arteries.[4,5] Venous embolization frequently originates from the large peripheral veins or the vena cava, embolizing to the right side of the heart, particularly to the right ventricle or pulmonary arteries.[4,6] In the present case, the right hepatic vein was believed to be the source of the embolus, though hepatic veins are rarely reported as a source for venous emboli origin, with a frequency of 0.9% in the literature.[4] Migrating venous foreign bodies lodge in the right ventricle more often than in the pulmonary arterial tree, as they tend to be trapped beneath the tricuspid valve or chordae tendinae, eventually encapsulated with fibrous tissue.[4,7] Following encapsulation, the foreign body may remain silent, as in the present case, or result in valvular dysfunction or myocardial instability. Only one-third of venous embolizations become symptomatic, with symptoms most commonly including dyspnea, chest pain, and hemoptysis.[8] Two rare venous embolization scenarios have been reported. The first is venous retrograde embolization, in which projectile movement contradicts normal venous blood flow, ocUlus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

curring in up to 15% of cases.[8,9] The second is paradoxical embolization, defined as the passage of a foreign body from the venous to the arterial vascular system through a rightto-left shunt. This shunt can occur in up to 10% of cases via patent foramen ovale ventricular septal defect, atrioventricular septal perforation, or arteriovenous fistula.[9,10] Although a paradoxical embolism originates from the venous system, it behaves as an arterial embolus. Bullet embolism should be suspected in any patient presenting with a gunshot entrance wound without exit wound, when signs and symptoms do not correlate with expected trajectory, and when radiographic location of a retained bullet changes during serial imaging.[7,11] X-ray, CT, and echocardiography can be utilized in the investigation of suspected foreign body embolism. X-rays can demonstrate the extent of bullet spread throughout the injury site. Chest x-ray is particularly important in the evaluation of patients with cardiopulmonary symptoms, as well as in asymptomatic patients, such as the present. If this basic investigation raises doubts regarding bullet embolism, CT and echocardiography should be performed. Serial CT scanning can assist in the detection of the embolic source. Echocardiography is vital in locating the bullet and defining the extent of cardiac trauma, thus aiding in the selection of the appropriate therapeutic option.[2,12] Advances in endovascular techniques and technology have increased use and success of bullet retrieval with a snare device since the method was first reported by Hartzler et al. in 1980.[7,13] However, conservative management may be suitable in cases of asymptomatic venous embolism and when endovascular retrieval has failed.[14] Conservative management requires regular follow-up, with special attention to possible indications of embolus complications.[15] Surgical removal of a foreign body is recommended in complicated cases, such as those with recurrent embolism and intractable infection, as well as in symptomatic cases in which endovascular approach fails or is unavailable.[16,17] However, pulmonary bullet emboli can be conservatively followed in the absence of pulmonary infarction, pulmonary abscess, or erosion in the bronchial tree.[14] Removal of intracardiac foreign body embolism has been recommended in some cases 397

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to avoid major venous obstruction, endocarditis, arrhythmia, valvular dysfunction, myocardial irritability, and delayed migration.[6,10] However, in recent years, conservative management of asymptomatic right-cardiac foreign body embolism has been favored by many authors.[2,15] Lundy et al. suggested that asymptomatic, firmly lodged, right-sided, smooth, <5 mm, or entirely intramyocardial emboli have a low risk, and that conservative management is suitable in these cases.[15]

Conclusion Following penetrating gunshot injury, the possibility of pellet migration to distant sites via the vascular system must be kept in mind. Clinical suspicion and radiological imaging techniques can assist in accurate diagnosis, reducing incidence of morbidity and mortality. Following definitive diagnosis, endovascular treatment should be considered, if applicable. In asymptomatic patients, conservative management and close follow-up (with echocardiography and chest x-ray) may be suitable. Conflict of interest: None declared.

REFERENCES 1. Nolan T, Phan H, Hardy AH, Khanna P, Dong P. Bullet embolization: multidisciplinary approach by interventional radiology and surgery. Semin Intervent Radiol 2012;29:192–6. 2. Hussein N, Rigby J, Abid Q. Bullet embolus to the right ventricle following shotgun wound to the leg. BMJ Case Rep 2012;2012. 3. Colquhoun IW, Jamieson MP, Pollock JC. Venous bullet embolism: a complication of airgun pellet injuries. Scott Med J 1991;36:16–7.

4. Springer J, Newman W, McGoey R. Intravascular bullet embolism to the right atrium. J Forensic Sci 2011;56 Suppl 1:S259–62. 5. Kurt N, Küçük HF, Celik G, Demirhan R, Celik G, Gül O, et al. Bullet embolism of the right external iliac artery following cardiac gunshot wound (a case report). Ulus Travma Derg 2001;7:131–3. 6. Patel KR, Cortes LE, Semel L, Sharma PV, Clauss RH. Bullet embolism. J Cardiovasc Surg (Torino) 1989;30:584–90. 7. Miller KR, Benns MV, Sciarretta JD, Harbrecht BG, Ross CB, Franklin GA, et al. The evolving management of venous bullet emboli: a case series and literature review. Injury 2011;42:441–6. 8. Schmelzer V, Mendez-Picon G, Gervin AS. Case report: transthoracic retrograde venous bullet embolization. J Trauma 1989;29:525–7. 9. Bining HJ, Artho GP, Vuong PD, Evans DC, Powell T. Venous bullet embolism to the right ventricle. Br J Radiol 2007;80:296–8. 10. Shannon FL, McCroskey BL, Moore EE, Moore FA. Venous bullet embolism: rationale for mandatory extraction. J Trauma 1987;27:1118–22. 11. Duncan IC, Fourie PA. Embolization of a bullet in the internal carotid artery. AJR Am J Roentgenol 2002;178:1572–3. 12. Soong W, Beckmann AK, Lin L, Ahmad US, McGee EC. Transesophageal echocardiography in the management of right ventricular bullet embolization from the left brachiocephalic vein. J Cardiothorac Vasc Anesth 2012;26:459–61. 13. Hartzler GO. Percutaneous transvenous removal of a bullet embolus to the right ventricle. J Thorac Cardiovasc Surg 1980;80:153–5. 14. Unkle D, Shaikh KA. Iliac vein to pulmonary artery missile embolus: case report and review of the literature. Heart Lung 1988;17:363–5. 15. Lundy JB, Johnson EK, Seery JM, Pham T, Frizzi JD, Chasen AB. Conservative management of retained cardiac missiles: case report and literature review. J Surg Educ 2009;66:228–35. 16. Grewal KS, Sintek CF, Jorgensen MB. Bullet embolism to the heart. Am Heart J 1997;133:468–70. 17. Kalimi R, Angus LD, Gerold T, DiGiacomo JC, Weltman D. Bullet embolization from the left internal iliac vein to the right ventricle. J Trauma 2002;52:772–4.

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Ateşli silah yaralanması sonrası saçma embolisi: Karaciğerden sağ ventriküle Dr. Selim Bakan,1 Dr. Bora Korkmazer,1 Dr. Ahmet Baş,1 Dr. Osman Şimşek,2 Dr. Hasan Ali Barman,3 Dr. Deniz Çebi Olgun1 İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul 3 İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Kardiyoloji Anabilim Dalı, İstanbul 1 2

Kardiyak saçma embolisi penetran travmalardan sonra görülen nadir ancak ciddi bir komplikasyondur. Ateşli silah yaralanması sonrası yabancı cisimlerin vasküler sistem aracılığı ile uzak migrasyonu dikkate alınmalıdır. Gecikmiş tanının sebep olabileceği yetersiz tedavi ve takip eden komplikasyonlar, kötü prognoz nedeni olabilir. Bu yazıda, konservatif olarak yaklaşılan semptomsuz kardiyak saçma embolisi olgusunu sunduk. Bu olgu sunumu penetran ateşli silah yaralanması sonrası saçma taneciğinin uzak migrasyon olasılığını ve semptomsuz hastalarda konservatif yaklaşımın önemini vurgulamaktadır. Anahtar sözcükler: Ateşli silah; kalp; saçma embolisi. Ulus Travma Acil Cerrahi Derg 2016;22(4):395–398

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A swallowed metal nail entrapped in the right psoas muscle İhsan Yıldız, M.D., Yavuz Savaş Koca, M.D., İbrahim Barut, M.D. Department of General Surgery, Süleyman Demirel University Faculty of Medicine, Isparta-Turkey

ABSTRACT Foreign body ingestion can be caused by many factors, including hallucination in patients with mental retardation. Most ingested foreign bodies are naturally discharged, though surgical intervention is necessary in some cases. Endoscopic intervention often leads to successful outcome, though open surgery may be required in certain instances. A 29-year-old mentally retarded woman presented to emergency services with a 2-day history of right lumbar pain that increased with movement. Physical examination revealed no specific sign beyond palpable tenderness in the right lumbar region. Radiological examination revealed a metal nail in the upper right quadrant, stretching obliquely toward the retroperitoneum. Endoscopy failed, and the nail was extracted via laparotomy. Foreign body ingestion may occur in patients of any age, but is more common in the pediatric population and in patients with mental retardation. Commonly ingested foreign bodies include daily objects, toys, and dentures, though they may differ in patients with mental retardation. The treatment of such cases requires a diversity of methods and experience. Foreign body ingestion should be kept in mind when a patient presents with pain in the right lumbar region, particularly in patients with mental retardation. Keywords: Duodenal perforation; swallowed foreign body.

INTRODUCTION Foreign body ingestion may intentionally or unintentionally occur. Unintentional foreign body ingestion is frequently observed in patients aged between 3 months and 6 years, as well as in the elderly population. However, it may also be the result of psychiatric disorders involving hallucination in patients with mental retardation. Cases of intentional foreign body ingestion have also been reported.[1,2] Commonly ingested objects include coins, needles, pins, jewelry, toy parts, teaspoons, nails, batteries, dentures, fish and chicken bones, and items used to handle food, such as lollipop sticks. These objects may be made of plastic, metal, or toxic material.[1–9] Most ingested foreign bodies are naturally discharged from the body within 4–6 days. However, serious complications in the gastrointestinal system such as obstruction or perforaAddress for correspondence: İhsan Yıldız, M.D. Süleyman Demirel Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 32100 Çünür, Isparta, Turkey Tel: +90 505 - 561 56 47 E-mail: drihsanyildiz@gmail.com Qucik Response Code

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tion may occur, requiring surgical intervention. These complications may also be associated with clinical presentations such as nausea, vomiting, and acute abdomen, depending on the location and severity of the obstruction and perforation. [1,5–9] Endoscopic approach is the method of choice in the treatment of ingested foreign bodies. However, laparoscopy and laparotomy may also be required in cases of perforation or obstruction.[2,5] Following foreign body retrieval, treatment of mental disorder, if applicable, in order to prevent repeated ingestion, is of prime importance.[1] Presently described were the clinical properties of a mentally retarded woman with repeated foreign body ingestion, who ingested a 12-cm nail, which became entrapped in the right psoas muscle after perforating the third portion of the duodenum. Also described were reported diagnostic and treatment approaches.

CASE REPORT A 29-year-old mentally retarded woman presented to the emergency department with a 2-day history of right lumbar pain. The family stated that the patient had a history of repeated foreign body ingestion. Physical examination revealed tenderness in the right lumbar on deep palpation. Results of other examinations were normal. White blood cell count was 12000 cells/mm3 and other parameters were normal. Direct abdominal radiography revealed a radiopaque impression of 399

Yıldız et al. A swallowed metal nail entrapped in the right psoas muscle

reported.[1] The present patient had psychiatric consultation in the early postoperative stage, upon the assumption that her mental retardation may have led to repeated foreign body ingestion.

Figure 1. Removing of swallowed nail from stomach is shown.

Figure 2. 12 cm metal nail removed is shown.

a metal nail in the upper right quadrant, directed downward (Fig. 1). Computed tomography showed a foreign body suggestive of a metal nail perforating the third portion of the duodenum and entrapped in the right psoas muscle (Fig. 1). Endoscopic intervention was attempted, though no contact was made with the nail. Laparotomy was performed under general anesthesia. Upon intraabdominal exploration, the inner abdomen was clean, the intestines were normal, and exploration confirmed that the nail had perforated the third portion of the duodenum and was entrapped in the right psoas muscle. The nail was manually mobilized into the stomach and extracted by gastrostomy, as endoscopic extraction may have caused damage to surrounding tissues. Following extraction, it was revealed that the nail and its metal structure had been impaired (Fig. 2). The duodenum was freed using Kocher’s maneuver, and the perforation tract was explored. No inflammation or localized peritonitis was observed. Surgery was concluded following insertion of a soft drain into the surgical site without impairment of the integrity of the fibrotic tract. The patient had psychiatric consultation and was discharged on the seventh postoperative day.

DISCUSSION Foreign body ingestion can occur accidentally or intentionally, and is most frequently observed in children at development stages and in patients with mental retardation.[1,2] In mentally retarded patients, cases similar to the present, of foreign body ingestion resulting from hallucination, have been 400

Foreign body ingestion and its complications are rare, though they remain a serious clinical problem. Most ingested objects are naturally discharged.[1] The period of extraction typically lasts for 5 days, depending on the size and structure of the ingested object. An orally ingested object passes through the oropharynx, pharynx, esophagus, cardia, pylorus, duodenum, small intestine, and colon, sometimes leading to obstruction and perforation at the anorectal level before penetrating into the rectoanal region.[5,7–9] Objects smaller than 6 cm and those with a structure thinner than 2 cm require no intervention and are naturally discharged.[5] In some cases, the ingested object remains in the body with no symptoms, and leads to unexpected complication after a long period. Misra et al. suggested that conservative treatment of asymptomatic cases is ideal, and that intervention should be performed following onset of first symptom.[1] Exact time of ingestion was unknown in the present case, though the patient’s family guessed that the nail had been ingested approximately 2 months prior, and that symptoms had begun 2 days prior to admission. Approximately 10–20% of ingested objects are extracted by endoscopy, while less than 1% require surgical intervention, performed in cases of perforation, obstruction, organ injury, and entrapment in surrounding tissues.[1,7–9] In the present patient, the nail was entrapped in the right psoas muscle after perforating the posterior wall of the third portion of the duodenum, with no sign of acute abdomen, a rare case. It was believed that perforations in the retroperitoneal area were not related to the peritoneum, and that pain was the result of movement of the nail caused by entrapment of the psoas muscle. Gastric and duodenal foreign bodies are often extracted by endoscopy.[2] However, endoscopic mobilization of the nail failed in the present case, and the nail was manually mobilized into the stomach through the duodenum. The nail was extracted after gastrostomy was performed on the anterior wall of the stomach, and the stomach was sutured. The duodenum was Kocherized, and the fibrotic tract was extensively dissected. However, the tract was not opened, as repair would have been difficult and may have lead to high-output fistula.

Conclusion Entrapment of an ingested nail in the psoas following closed duodenal perforation is a very rare clinical occurrence. As evidenced by the present case, foreign body ingestion should be considered when patients present with pain in the right lumbar region without indication of obstruction or acute abdomen, particularly in cases of mental retardation. Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Yıldız et al. A swallowed metal nail entrapped in the right psoas muscle

Conflict of interest: None declared.

REFERENCES 1. Misra S, Jain V, Ahmad F, Kumar R, Kishore N. Metallic sewing needle ingestion presenting as acute abdomen. Niger J Clin Pract 2013;16:540– 3. 2. Sai Prasad TR, Low Y, Tan CE, Jacobsen AS. Swallowed foreign bodies in children: report of four unusual cases. Ann Acad Med Singapore 2006;35:49–53. 3. Nijhawan S, Kumpawat S, Ashdhir P, Behl N, Jha A, Rai RR. Impacted nail in duodenum: endoscopic removal with a novel magnetic foreign body retriever. Endoscopy 2009;41 Suppl 2:62. 4. Hayek G, D’Assignies G. Images in clinical medicine. An unknowingly

swallowed inedible toy. N Engl J Med 2013;369:2535. 5. Cho EA, Lee du H, Hong HJ, Park CH, Park SY, Kim HS, et al. An unusual case of duodenal perforation caused by a lollipop stick: a case report. Clin Endosc 2014;47:188–91. 6. Kim MJ, Seo JM, Lee Y, Lee YM, Choe YH. An unusual cause of duodenal perforation due to a lollipop stick. Korean J Pediatr 2013;56:182–5. 7. Başpinar I, Sahin S, Erdoğan G. Acute mechanical intestinal obstruction after ingestion of foreign bodies: a case report. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2010;16:92–4. 8. Celik S, Aydemir B, Tanrıkulu H, Okay T, Doğusoy I. Esophageal foreign bodies in children and adults: 20 years experience. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2013;19:229–34. 9. Cobanoğlu U, Yalçinkaya I. Tracheobronchial foreign body aspirations. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2009;15:493–9.

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Sağ psoas kasına saplanan yutulmuş çivi Dr. İhsan Yıldız, Dr. Yavuz Savaş Koca, Dr. İbrahim Barut Süleyman Demirel Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Isparta

Yabancı cisim yutulması bilinçsiz ya da bilinçli olabilmektedir. Bilinçsiz olanların çoğu, üç ay–altı yaş arası çocuklarda, çok ileri yaşlarda, kazayla veya mental problemli kişilerde halüsinasyon gibi bir nedenle olabilmektedir. Bu cismlerin çoğu doğal yoldan atılmaktadır. İki gündür sağ lomber bölgede hareketle artan ağrı şikayeti ile acil servise getirilen, 29 yaşındaki mental retarde kadın hastanın fizik incelemesinde palpasyonla sağ lomber hassasiyet dışında bir özellik yoktu. Yapılan radyolojik değerlendirmede sağ üst kadranda retroperitona oblik olarak uzanım gösteren ve endoskopik olarak çıkartılamayan metal çivi laparotomi yapılarak çıkarıldı. Yabancı cisim yutulması birçok nedenle olabilmektedir. Mental retarde hastalarda halüsinasyonla yabancı cisim yutulması bildirilmekte ve aynı şekilde bizim hastamız da mental retarde idi. Ancak yutulan cisimin akut karın oluşturmadan sağ yan ağrısına neden olması olası bir komplikasyon olarak akılda tutulmalıdır. Özellikle mental retarde hastalarda olmak üzere sağ yan ağrısı ile gelen hastalarda yabancı cisim yutulması akılda tutulmalıdır. Anahtar sözcükler: Duodenum perforasyonu; yabancı cisim yutulması. Ulus Travma Acil Cerrahi Derg 2016;22(4):399–401

doi: 10.5505/tjtes.2015.66814

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Pencil in the pharynx: Case report of a penetrating foreign body İrfan Kara, M.D.,1 Halil Ulutabanca, M.D.,2 Kerem Kökoğlu, M.D.,1 Murat Salih Güneş, M.D.,3 Sedat Çağlı, M.D.1 1

Department of Otolaryngology-Head and Neck Surgery, Erciyes University Faculty of Medicine, Kayseri-Turkey

Department of Neurosurgery, Erciyes University Faculty of Medicine, Kayseri-Turkey

3Department of Otolaryngology, Kayseri Training and Research Hospital, Kayseri-Turkey

ABSTRACT Pharyngeal foreign bodies are commonly encountered in otolaryngological practice. However, in certain instances, particularly in cases of penetrating injuries, major vascular damage leads to severe morbidity and mortality. Management of these cases includes airway protection, bleeding control, imaging of major vascular injury, and prophylactic antibiotics.The case of a 2-year-old patient with penetrating pharyngeal foreign body is described in the present report. Key words: Foreign body; oropharynx; penetrating injury.

INTRODUCTION Foreign body cases are common in otolaryngological practice, usually occurring in children.[1,2] Foreign bodies are often observed in the ear and nose, while pharyngeal foreign bodies are less common. Presently described is the management of penetrating pharyngeal foreign body injury in a 2-year-old boy, as well as current references in the literature.

CASE REPORT A 2-year-old boy fell prone while playing, with a pencil in his mouth, and the pencil penetrated his pharynx. Upon admission to the emergency department, his vital signs were normal, but he was anxious. When clots in the oral cavity were removed, no bleeding was observed in the oropharynx. The pencil was located behind the right posterior plica (Fig. 1a, b). The other end of the pencil was palpable in the right Address for correspondence: Kerem Kökoğlu, M.D. Erciyes Üniversitei Tıp Fakültesi, Kulak Burun Boğaz Hastalıkları Anabilim Dalı, Kayseri, Turkey Tel: +90 352 - 207 66 66 E-mail: dr.kokoglu@gmail.com Qucik Response Code

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occipital area, but the skin was intact (Fig. 1c). Neurological examination was normal. Upon computed tomography (CT) and CT angiography examinations, a foreign body was observed through the right posterior pharyngeal area, reaching the right occipital area. The foreign body was on the medial side of the internal carotid artery and very near the right vertebral artery. No vascular injury, aneurysm, or extravasation was observed (Fig. 1d, e). Removal of the foreign body in the operating room by otolaryngology and neurosurgery teams was planned. Due to the possibility of intubation failure, tracheotomy conditions were prepared. Orotracheal intubation was successful, and the pencil was carefully removed. Only blood leakage was observed. The wound was sutured (Fig. 1f, g). The patient remained in the intensive care unit for 1 day. Broad-spectrum antibiotics (ampicillin, sulbactam, and clindamycin) were administered. Bleeding and respiratory distress were not observed at follow-up. Oral feeding was initiated at the 48th postoperative hour. The patient was externed on the 3rd day. No complication was observed.

DISCUSSION Pharyngeal foreign bodies frequently occur in children. A child with acute respiratory distress and abundant secretion who refuses food and drink must be suspected of pharyngeal foreign body.[3] Neck examination must be performed in such cases, during which the foreign body may be palpated, and emphysema and edema may be observed.[4] Patients with Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

Kara et al. Pencil in the pharynx

(a)

(d)

(b)

(e)

(c)

(f)

(g)

Figure 1. (a) Penetrated pencil is seen in the mouth. (b) Closer sight of the pencil. (c) Arrow points to end of the pencil reaching occipital area. (d) CT imaging. Foreign body and vascular structures are seen. Arrow points to carotid arter. (e) 3-D CT imaging. Upper arrow points to foreign body and below arrow points to carotid arter. (f) Oropharynx after removing the pencil. (g) Sutured area in the oropharynx.

acute respiratory distress due to foreign body may be mistakenly diagnosed with croup.[3] Penetrating pharyngeal injuries usually occur in children who fall prone while walking with a foreign body in their mouths. [5,6] This injury is most frequently observed in boys, with a boy:girl ratio of 3:1. However, exact data regarding frequency of this injury is not available.[5] The most frequently observed foreign bodies are toothbrushes, cylindrical toys, and pencils. [5] In penetrating pharyngeal injuries, the soft palate and tonsils are usually affected. Injuries to the hard palate, tongue, and posterior oropharyngeal area are less common.[5] In the present case, the foreign body penetrated through the posterior pharyngeal wall. The pharynx of a child is soft, and foreign bodies can pass easily through the posterior wall, injuring the carotid artery. If severe injury is suspected, 3-dimensional CT must be performed instead of simple removal procedure. CT angiography may be performed, when necessary, to exclude major vascular injuries.[4] In the present patient, major vascular injury was excluded by CT and CT angiography prior to removal of the pencil. In penetrating pharyngeal injuries, severe complications are rare, though morbidity and mortality have resulted in some Ulus Travma Acil Cerrahi Derg, July 2016, Vol. 22, No. 4

cases.[7] Carotid artery damage, neurological sequels due to thrombosis, airway obstructions, sepsis, shock, cervical emphysema, pneumothorax, and pneumomediastinum are severe potential complications.[4,8] Bleeding can be severe, requiring urgent repair. In these cases, consultation with a cardiovascular surgery team is necessary. If repair cannot be performed, carotid artery ligation must be considered as a last resort.[4] Management of these cases varies. The patient must be followed for at least 72 hours, and oral feeding must be stopped, due to possibility of reoperation. Prophylactic antibiotics must be administered.[6] In present case, oral feeding was stopped, antibiotics were administered, and the patient was followed for 72 hours. Pharyngeal foreign body is a medical emergency.[3] Delay of intervention can cause respiratory distress, due to edema and infection such as retropharyngeal abscess. Early intervention must be performed to prevent development of aspiration and edema.[3] During intervention, tracheotomy conditions must be prepared.[9]

Conclusion In cases of penetrating pharyngeal injuries, severe compli403

Kara et al. Pencil in the pharynx

cations are rare, but may result in morbidity and mortality. The pharynx of a child is soft– foreign bodies can easily pass through the posterior wall, injuring the carotid artery. Due to the possibility of major vascular injury, 3-dimensional imaging and angiography must be performed when necessary. Intervention must take place under general anesthesia,and tracheotomy conditions must be prepared. Conflict of interest: None declared.

REFERENCES 1. Coskun BU, Sözen E, Ünsal Ö, Dadaş B. Ear, nose and upper gastrointestinal system foreign bodies in children. Türk Otolarengoloji Arşivi 2006;44:77–80. 2. Chiun KC, Tang IP, Tan TY, Jong DE. Review of ear, nose and throat foreign bodies in Sarawak General Hospital. A five year experience. Med J Malaysia 2012;67:17–20.

3. Heim SW, Maughan KL. Foreign bodies in the ear, nose, and throat. Am Fam Physician 2007;76:1185–9. 4. Sasaki T, Toriumi S, Asakage T, Kaga K, Yamaguchi D, Yahagi N. The toothbrush: a rare but potentially life-threatening cause of penetrating oropharyngeal trauma in children. Pediatrics 2006;118(4):1284–6. 5. Chauhan N, Guillemaud J, El-Hakim H. Two patterns of impalement injury to the oral cavity: Report of four cases and review of literature. Int J Pediatr Otorhinolaryngol 2006;70:1479–83. 6. Younessi OJ, Alcaino EA. Impalement injuries of the oral cavity in children: a case report and survey of the literature. Int J Paediatr Dent 2007;17:66–71. 7. Kosaki H, Nakamura N, Toriyama Y. Penetrating injuries to the oropharynx. J Laryngol Otol 1992;106:813–6. 8. Patel N, McVeigh K, Sharma P, Parmer S. An impalement injury to the oropharynx in a paediatric patient--a case report. Br J Oral Maxillofac Surg 2011;49:12–3. 9. Sagar S, Kumar N, Singhal M, Kumar S, Kumar A. A rare case of lifethreatening penetrating oropharyngeal trauma caused by toothbrush in a child. J Indian Soc Pedod Prev Dent 2010;28:134–6.

OLGU SUNUMU - ÖZET

Farinkste kalem: Delici bir yaralanmanın olgu sunumu Dr. İrfan Kara,1 Dr. Halil Ulutabanca,2 Dr. Kerem Kökoğlu,1 Dr. Murat Salih Güneş,1 Dr. Sedat Çağlı1 1 2

Erciyes Üniversitesi Tıp Fakültesi, Kulak Burun Boğaz Hastalıkları - Baş Boyun Cerrahi Anabilim Dalı, Kayseri Erciyes Üniversitesi Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Kayseri

Faringeal yabancı cisimlere kulak burun boğaz hastalıkları pratiğinde sık rastlanılır. Ancak özellikle delici yabancı cisimlerde büyük damar yaralanmasına yol açarak ciddi morbidite ve mortalite sebebi olabilirler. Bu hastaların yönetimi havayolunun korunması, kanamanın kontrolü, büyük damar yaralanmasının görüntülenmesi ve profilaktik antibiyotiği içerir. Yazıda, iki yaşında bir delici faringeal yabancı cisim olgusu ve eşliğinde bu olgulara yaklaşım sunulmuştur. Anahtar sözcükler: Delici yaralanma; orofarinks; yabancı cisim. Ulus Travma Acil Cerrahi Derg 2016;22(4):402–404

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