Travma 2017 / 5

ISSN 1306 - 696X

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

Volume 23 | Number 5 | September 2017

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Recep Güloğlu Editors Kaya Sarıbeyoğlu (Managing Editor) M. Mahir Özmen Hakan Yanar Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu Section Editors Anaesthesiology & ICU Güniz Meyancı Köksal, Mert Şentürk Cardiac Surgery Münacettin Ceviz, Murat Güvener Neurosurgery Ahmet Deniz Belen, Mehmet Yaşar Kaynar Ophtalmology Cem Mocan, Halil Ateş Ortopedics and Traumatology Mahmut Nedim Doral, Mehmet Can Ünlü Plastic and Reconstructive Surgery Ufuk Emekli, Figen Özgür Pediatric Surgery Aydın Yagmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu

www.tjtes.org

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

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

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

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

ISSUED BY THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ YAYIN ORGANI Owner (Ulusal Travma ve Acil Cerrahi Derneği adına Sahibi) Editorial Director (Yazı İşleri Müdürü) Managing Editor (Yayın Koordinatörü) 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): Suzan Atwood • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): September (Eylül) 2017 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE P U B L I S H I N G

www.tjtes.org

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

tion, called “Upload Your Files”.

As from 2001, the journal is indexed in Index Medicus and Medline, as from 2005 in Excerpta Medica and EMBASE, as from 2007 in Science Citation Index Expanded (SCI-E) and Journal Citation Reports / Science Edition, and as from 2014 in EBSCOhost. Our impact factor in SCI-E indexed journals is 0.473 (JCR 2016). It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PubMed.

Figures, illustrations and tables: All figures and tables should be numbered in the order of appearance in the text. The desired position of figures and tables should be indicated in the text. Legends should be included in the relevant part of the main text and those for photomicrographs and slide preparations should indicate the magnification and the stain used. Color pictures and figures will be published if they are definitely required and with the understanding that the authors are prepared to bear the costs. Line drawings should be professionally prepared. For recognizable photographs, signed releases of the patient or of his/her legal representatives should be enclosed; otherwise, patient names or eyes must be blocked out to prevent identification.

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

Manuscripts must be submitted in English. All submissions are initially reviewed by the editor, and then are sent to reviewers. All manuscripts are subject to editing and, if necessary, will be returned to the authors for answered responses to outstanding questions or for addition of any missing information to be added. For accuracy and clarity, a detailed manuscript editing is undertaken for all manuscripts accepted for publication. Final galley proofs are sent to the authors for approval.

Unless specifically indicated otherwise at the time of submission, rejected manuscripts will not be returned to the authors, including accompanying materials.

TJTES is indexed in Science Citation Index-Expanded (SCI-E), Index Medicus, Medline, EMBASE, Excerpta Medica, and the Turkish Medical Index of TUBITAK-ULAKBIM. Priority of publications is given to original studies; therefore, selection criteria are more refined for reviews and case reports.

Open Access Policy: Full text access is free. There is no charge for publication or downloading the full text of printed material.

Manuscript submission: TJTES accepts only on-line submission via the official web site (please click, www.travma.org.tr/en) and refuses printed manuscript submissions by mail. All submissions are made by the on-line submission system called Journal Agent, by clicking the icon “Online manuscript submission” at the above mentioned web site homepage. The system includes directions at each step but for further information you may visit the web site (http://www.travma.org/en/ journal/).

Manuscript preparation: Manuscripts should have double-line spacing, leaving sufficient margin on both sides. The font size (12 points) and style (Times New Roman) of the main text should be uniformly taken into account. All pages of the main text should be numbered consecutively. Cover letter, manuscript title, author names and institutions and correspondence address, abstract in Turkish (for Turkish authors only), and title and abstract in English are uploaded to the Journal Agent system in the relevant steps. The main text includes Introduction, Materials and Methods, Results, Discussion, Acknowledgments, References, Tables and Figure Legends.

The cover letter must contain a brief statement that the manuscript has been read and approved by all authors, that it has not been submitted to, or is not under consideration for publication in, another journal.

It should contain the names and signatures of all authors. The cover letter is uploaded at the 10th step of the “Submit New Manuscript” sec-

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

References: All references should be numbered in the order of mention in the text. All reference figures in the text should be given in brackets without changing the font size. References should only include articles that have been published or accepted for publication. Reference format should conform to the “Uniform requirements for manuscripts submitted to biomedical journals” (http://www.icmje.org) and its updated versions (February 2006). Journal titles should be abbreviated according to Index Medicus. Journal references should provide inclusive page numbers. All authors, if six or fewer, should be listed; otherwise the first six should be listed, followed by “et al.” should be written. The style and punctuation of the references should follow the formats below: Journal article: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5.

Chapter in book: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62.

Our journal has succeeded in being included in several indexes, in this context, we have included a search engine in our web site (www. travma.org.tr) so that you can access full-text articles of the previous issues and cite the published articles in your studies.

Review articles: Only reviews written by distinguished authors based on the editor’s invitation will be considered and evaluated. Review articles must include the title, summary, text, and references sections.

Any accompanying tables, graphics, and figures should be prepared as mentioned above.

Case reports: A limited number of case reports are published in each issue of the journal. The presented case(s) should be educative and of interest to the readers, and should reflect an exclusive rarity. Case reports should contain the title, summary, and the case, discussion, and references sections. These reports may consist of maximum five authors.

Letters to the Editor: “Letters to the Editor” are only published electronically and they do not appear in the printed version of TJTES and PUBMED. The editors do not issue an acceptance document as an original article for the ‘’letters to the editor. The letters should not exceed 500 words. The letter must clearly list the title, authors, publication date, issue number, and inclusive page numbers of the publication for which opinions are released.

Informed consent - Ethics: Manuscripts reporting the results of experimental studies on human subjects must include a statement that informed consent was obtained after the nature of the procedure(s) had been fully explained. Manuscripts describing investigations in animals must clearly indicate the steps taken to eliminate pain and suffering. Authors are advised to comply with internationally accepted guidelines, stating such compliance in their manuscripts and to include the approval by the local institutional human research committee.

YAZARLARA BİLGİ Ulusal Travma ve Acil Cerrahi Dergisi, Ulusal Travma ve Acil Cerrahi Derneği’nin yayın organıdır. Travma ve acil cerrahi hastalıklar konularında bilimsel birikime katkısı olan klinik ve deneysel çalışmaları, editöryel yazıları, klinik olgu sunumlarını ve bu konulardaki teknik katkılar ile son gelişmeleri yayınlar. Dergi iki ayda bir yayınlanır.

Ulusal Travma ve Acil Cerrahi Dergisi TÜBİTAK TR Dizinde taranmaktadır, ayrıca uluslararası indekslerde, 2001 yılından itibaren Index Medicus, PubMed’de, 2005 yılından itibaren EMBASE’de, 2007 yılından itibaren Web of Science, Science Citation Index-Expanded’de (SCI-E), 2014 yılından itibaren de EBSCOhost indeksinde dizinlenmektedir. 2016 Journal Citation Report IF puanımız artarak 0.473 olmuştur. Dergide araştırma yazılarına öncelik verilmekte, bu nedenle derleme veya olgu sunumu türündeki yazılarda seçim ölçütleri daha dar tutulmaktadır. PUBMED’de dergi “Ulus Travma Acil Cerrahi Derg” kısaltması ile yer almaktadır.

Dergiye yazı teslimi, çalışmanın daha önce yayınlanmadığı (özet ya da bir sunu, inceleme, ya da tezin bir parçası şeklinde yayınlanması dışında), başka bir yerde yayınlanmasının düşünülmediği ve Ulusal Travma ve Acil Cerrahi Dergisi’nde yayınlanmasının tüm yazarlar tarafından uygun bulunduğu anlamına gelmektedir. Yazar(lar), çalışmanın yayınlanmasının kabulünden başlayarak, yazıya ait her hakkı Ulusal Travma ve Acil Cerrahi Derneği’ne devretmektedir(ler). Yazar(lar), izin almaksızın çalışmayı başka bir dilde ya da yerde yayınlamayacaklarını kabul eder(ler). Gönderilen yazı daha önce herhangi bir toplantıda sunulmuş ise, toplantı adı, tarihi ve düzenlendiği şehir belirtilmelidir.

Dergide İngilizce yazılmış makaleler yayınlanır. Tüm yazılar önce editör tarafından ön değerlendirmeye alınır; daha sonra incelenmesi için danışma kurulu üyelerine gönderilir.

Tüm yazılarda editöryel değerlendirme ve düzeltmeye başvurulur; gerektiğinde, yazarlardan bazı soruları yanıtlanması ve eksikleri tamamlanması istenebilir. Dergide yayınlanmasına karar verilen yazılar “manuscript editing” sürecine alınır; bu aşamada tüm bilgilerin doğruluğu için ayrıntılı kontrol ve denetimden geçirilir; yayın öncesi şekline getirilerek yazarların kontrolüne ve onayına sunulur. Editörün, kabul edilmeyen yazıların bütününü ya da bir bölümünü (tablo, resim, vs.) iade etme zorunluluğu yoktur.

Açık Erişim İlkesi: Tam metinlere erişim ücretsizdir. Yayınlanan basılı materyali tam metni indirmek için herhangi bir ücret alınmaz.

Yazıların hazırlanması: Tüm yazılı metinler 12 punto büyüklükte “Times New Roman” yazı karakterinde iki satır aralıklı olarak yazılmalıdır. Sayfada her iki tarafta uygun miktarda boşluk bırakılmalı ve ana metindeki sayfalar numaralandırılmalıdır. Journal Agent sisteminde, başvuru mektubu, başlık, yazarlar ve kurumları, iletişim adresi, Türkçe özet ve yazının İngilizce başlığı ve özeti ilgili aşamalarda yüklenecektir. İngilizce yazılan çalışmalara da Türkçe özet eklenmesi gerekmektedir. Yazının ana metnindeyse şu sıra kullanılacaktır: Giriş, Gereç ve Yöntem, Bulgular, Tartışma, Teşekkür, Kaynaklar, Tablolar ve Şekiller.

Başvuru mektubu: Bu mektupta yazının tüm yazarlar tarafından okunduğu, onaylandığı ve orijinal bir çalışma ürünü olduğu ifade edilmeli ve yazar isimlerinin yanında imzaları bulunmalıdır. Başvuru mektubu ayrı bir dosya olarak, Journal Agent sisteminin “Yeni Makale Gönder” bölümünde, 10. aşamada yer alan dosya yükleme aşamasında yollanmalıdır.

Başlık sayfası: Yazının başlığı, yazarların adı, soyadı ve ünvanları, çalışmanın yapıldığı kurumun adı ve şehri, eğer varsa çalışmayı destekleyen fon ve kuruluşların açık adları bu sayfada yer almalıdır. Bu sayfaya ayrıca “yazışmadan sorumlu” yazarın isim, açık adres, telefon, faks, mobil telefon ve e-posta bilgileri eklenmelidir. Özet: Çalışmanın gereç ve yöntemini ve bulgularını tanıtıcı olmalıdır.

Türkçe özet, Amaç, Gereç ve Yöntem, Bulgular, Sonuç ve Anahtar Sözcükler başlıklarını; İngilizce özet Background, Methods, Results, Conclusion ve Key words başlıklarını içermelidir. İngilizce olarak hazırlanan çalışmalarda da Türkçe özet yer almalıdır. Özetler başlıklar hariç 190210 sözcük olmalıdır.

Tablo, şekil, grafik ve resimler: Şekillere ait numara ve açıklayıcı bilgiler ana metinde ilgili bölüme yazılmalıdır. Mikroskobik şekillerde resmi açıklayıcı bilgilere ek olarak, büyütme oranı ve kullanılan boyama tekniği de belirtilmelidir. Yazarlara ait olmayan, başka kaynaklarca daha önce yayınlanmış tüm resim, şekil ve tablolar için yayın hakkına sahip kişilerden izin alınmalı ve izin belgesi dergi editörlüğüne ayrıca açıklamasıyla

birlikte gönderilmelidir. Hastaların görüntülendiği fotoğraflara, hastanın ve/veya velisinin imzaladığı bir izin belgesi eşlik etmeli veya fotoğrafta hastanın yüzü tanınmayacak şekilde kapatılmış olmalıdır. Renkli resim ve şekillerin basımı için karar hakemler ve editöre aittir. Yazarlar renkli baskının hazırlık aşamasındaki tutarını ödemeyi kabul etmelidirler.

Kaynaklar: Metin içindeki kullanım sırasına göre düzenlenmelidir. Makale içinde geçen kaynak numaraları köşeli parantezle ve küçültülmeden belirtilmelidir. Kaynak listesinde yalnızca yayınlanmış ya da yayınlanması kabul edilmiş çalışmalar yer almalıdır. Kaynak bildirme “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (http:// www.icmje.org) adlı kılavuzun en son güncellenmiş şekline (Şubat 2006) uymalıdır. Dergi adları Index Medicus’a uygun şekilde kısaltılmalıdır. Altı ya da daha az sayıda olduğunda tüm yazar adları verilmeli, daha çok yazar durumunda altıncı yazarın arkasından “et al.” ya da “ve ark.” eklenmelidir. Kaynakların dizilme şekli ve noktalamalar aşağıdaki örneklere uygun olmalıdır: Dergi metni için örnek: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5.

Kitaptan bölüm için örnek: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62.

Sizlerin çalışmalarınızda kaynak olarak yararlanabilmeniz için www.travma.org.tr adresli web sayfamızda eski yayınlara tam metin olarak ulaşabileceğiniz bir arama motoru vardır.

Derleme yazıları: Bu tür makaleler editörler kurulu tarafından gerek olduğunda, konu hakkında birikimi olan ve bu birikimi literatüre de yansımış kişilerden talep edilecek ve dergi yazım kurallarına uygunluğu saptandıktan sonra değerlendirmeye alınacaktır. Derleme makaleleri; başlık, Türkçe özet, İngilizce başlık ve özet, alt başlıklarla bölümlendirilmiş metin ile kaynakları içermelidir. Tablo, şekil, grafik veya resim varsa yukarıda belirtildiği şekilde gönderilmelidir.

Olgu sunumları: Derginin her sayısında sınırlı sayıda olgu sunumuna yer verilmektedir. Olgu bildirilerinin kabulünde, az görülürlük, eğitici olma, ilginç olma önemli ölçüt değerlerdir. Ayrıca bu tür yazıların olabildiğince kısa hazırlanması gerekir. Olgu sunumları başlık, Türkçe özet, İngilizce başlık ve özet, olgu sunumu, tartışma ve kaynaklar bölümlerinden oluşmalıdır. Bu tür çalışmalarda en fazla 5 yazara yer verilmesine özen gösterilmelidir.

Editöre mektuplar: Editöre mektuplar basılı dergide ve PUBMED’de yer almamakta, ancak derginin web sitesinde yayınlanmaktadır. Bu mektuplar için dergi yönetimi tarafından yayın belgesi verilmemektedir.

Daha önce basılmış yazılarla ilgili görüş, katkı, eleştiriler ya da farklı bir konu üzerindeki deneyim ve düşünceler için editöre mektup yazılabilir.

Bu tür yazılar 500 sözcüğü geçmemeli ve tıbbi etik kurallara uygun olarak kaleme alınmış olmalıdır. Mektup basılmış bir yazı hakkında ise, söz konusu yayına ait yıl, sayı, sayfa numaraları, yazı başlığı ve yazarların adları belirtilmelidir. Mektup bir konuda deneyim, düşünce hakkında ise verilen bilgiler doğrultusunda dergi kurallarına uyumlu olarak kaynaklar da belirtilmelidir.

Bilgilendirerek onay alma - Etik: Deneysel çalışmaların sonuçlarını bildiren yazılarda, çalışmanın yapıldığı gönüllü ya da hastalara uygulanacak prosedür(lerin) özelliği tümüyle anlatıldıktan sonra, onaylarının alındığını gösterir bir cümle bulunmalıdır. Yazarlar, bu tür bir çalışma söz konusu olduğunda, uluslararası alanda kabul edilen kılavuzlara ve T.C. Sağlık Bakanlığı tarafından getirilen yönetmelik ve yazılarda belirtilen hükümlere uyulduğunu belirtmeli ve kurumdan aldıkları Etik Komitesi onayını göndermelidir. Hayvanlar üzerinde yapılan çalışmalarda ağrı, acı ve rahatsızlık verilmemesi için neler yapıldığı açık bir şekilde belirtilmelidir.

Yazı gönderme - Yazıların gönderilmesi: Ulusal Travma ve Acil Cerrahi Dergisi yalnızca www.travma.org.tr adresindeki internet sitesinden on-line olarak gönderilen yazıları kabul etmekte, posta yoluyla yollanan yazıları değerlendirmeye almamaktadır. Tüm yazılar ilgili adresteki “Online Makale Gönderme” ikonuna tıklandığında ulaşılan Journal Agent sisteminden yollanmaktadır. Sistem her aşamada kullanıcıyı bilgilendiren özelliktedir.

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 23

Number - Sayı 5 September - Eylül 2017

Contents - İçindekiler Deneysel Review - Çalışma Derleme - Experimental Study 357-361 Topical hemostatics for bleeding control in pre-hospital setting: Then and now

Kanamalara hastane öncesi müdahale sırasında kullanılan topikal hemostatikler: Öncesi ve şimdi Güven HE

Experimental Studies - Deneysel Çalışma 362-367 Evaluation of different treatment protocols for combined injury-induced lung injury in rabbits

Tavşanlarda kombine travmanın neden olduğu akciğer yaralanmasında farklı tedavi protokollerinin değerlendirilmesi Li XB 368-376 Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

Deneysel künt toraks travma modelinde levosimendanın sistemik antienflamatuvar etkilerinin araştırılması Ateş G, Yaman F, Bakar B, Kısa Ü, Atasoy P, Büyükkoçak Ü 377-382 Separate and synergistic effects of taurolidine and icodextrin in intra-abdominal adhesion prevention

Taurolidin ve icodextrin’in intraabdominal yapışıklıkların önlenmesinde ayrı ve sinerjik etkileri Kurt N, Sıkar HE, Kaptanoğlu L, Küçük HF

Original Articles - Orijinal Çalışma 383-388 Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

Konvansiyonel skorlama sistemleri ile nekrotizan fasiitisli hastalarda mortaliteyi öngörebilir miyiz?

Yaşar NF, Uylaş MU, Badak B, Bilge U, Öner S, İhtiyar E, Çağa T, Paşaoğlu E 389-394 Usefulness of FGSI and UFGSI scoring systems for predicting mortality in patients with Fournier’s gangrene: A multicenter study

Fournier gangrenli hastalarda mortalite tahmininde FGSİ ve UFGSİ skorlama sistemlerinin prediktif değeri: Çok merkezli çalışma Üreyen O, Acar A, Gökçelli U, Atahan MK, İlhan E 395-399 Managing endoscopic retrograde cholangiopancreatography-related complications in patients referred to the surgical emergency unit

Bir acil cerrahi kliniğinin endoskopik retrograd kolanjiopankreatografi komplikasyonları ile ilgili deneyimi Şimşek O, Şimşek A, Ergun S, Velidedeoğlu M, Sarıbeyoğlu K, Pekmezci S 400-404 Fournier’s gangrene: A retrospective analysis of 25 patients

Fournier gangreni: 25 hastanın geriye dönük analizi Yücel M, Özpek A, Başak F, Kılıç A, Ünal E, Yüksekdağ S, Acar A, Baş G

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 23

Number - Sayı 5 September - Eylül 2017

Contents - İçindekiler

405-409 Primary exploration for radial nerve palsy associated with unstable closed humeral shaft fracture

Kararlı olmayan kapalı humerus cismi kırığı ile ilişkili radiyal sinir felcinin primer eksplorasyonu Han SH, Hong IT, Lee HJ, Lee SJ, Kim U, Kim DW 410-414 Long-term results of primary repair of combined cuts on the median and ulnar nerves in the forearm

Ön kol seviyesinde median ulnar sinir kombine kesilerinin primer tamirinin uzun dönem sonuçları Özaksar K, Günay H, Küçük L, Coşkunol E 415-420 ESIN and K-wire fixation have similar results in pediatric both-bone diaphyseal forearm fractures

Çocuk önkol çift kırıklarında ESIN ve K-teli tespiti benzer sonuçlara sahiptir Şahin N, Akalın Y, Türker O, Özkaya G

Case Series - Olgu Serisi 421-426 Diaphragmatic rupture: A single-institution experience and literature review

Diyafragma rüptürü: Tek bir kurum deneyimi ve literatürün gözden geçirilmesi Corbellini C, Costa S, Canini T, Villa R, M.D., Avesani EC

Case Report - Olgu Sunumu 427-429 Klingsor syndrome: A rare surgical emergency

Klingsor sendromu: Seyrek görülen cerrahi acil Aggarwal G, Adhikary SD 430-432 Traumatic duodenal injury in children: A report of two cases

Çocuklarda travmatik duodenal transeksiyon: İki olgu sunumu Makhija D, Jayaswal S, Kumbhar V, Shah H 433-437 Emergency endovascular treatment of a ruptured external carotid artery pseudoaneurysm caused by a cervical stab wound: A case report and literature review

Servikal penetran yaranın neden olduğu eksternal karotis arter psödoanevrizması rüptürünün acil endovasküler tedavisi: Bir olgu raporu ve literatürün gözden geçirilmesi Tsurukiri J, Okumura E, Yamanaka H, Jimbo H, Hoshiai A 438-440 Laparoscopic approach for removing a coin trapped in Meckel’s diverticulum

Meckel divertikülü içine hapsolmuş bozuk para olgusuna laparoskopik yaklaşım Karadeniz Cerit K, Kalyoncu A, Erbarut İ, Kıyan G, Dağlı TE 441-444 Role of percutaneous transhepatic biliary drainage in the management of blunt liver trauma: A case report

Karaciğer künt travma yönetiminde perkütan biliyer drenajın rolü: Olgu sunumu Oğuz Ş, Yıldırım R, Topaloğlu S

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RE VI EW

Topical hemostatics for bleeding control in pre-hospital setting: Then and now H. Erhan Güven, M.D. Department of General Surgery, University of Health Sciences Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT Massive hemorrhage causes instant and early deaths because of hypovolemia. However, even if the victim makes it to the hospital, hypothermia, metabolic acidosis, and coagulation impairments caused by bleeding pose a great risk for survival. Many topical hemostatic agents are developed for neck, armpit, or groin injuries that are not amenable to tourniquet application and for extremity wounds to be used in conjunction with tourniquets. This paper focuses on those hemostatics that differ based on the action mechanism and are suitable for pre-hospital setting and summarizes the latest recommendations regarding their usage.

Keywords: Bleeding; pre-hospital; topical hemostatics.

INTRODUCTION Every bleeding eventually stops. However this fact gives no relief to any surgeon in the operating room or medical personnel on the field dealing with hemorrhage. Bleeding causes death not only from hypovolemia and exsanguination at the scene but also from uncorrectable metabolic acidosis, hypothermia, multiple organ failure, and coagulation disorders that are resistant to transfusions even after the victim is hospitalized.

The latest data on this topic is derived from US combat soldiers wounded during the Iraq and Afghanistan campaigns between 2001 and 2011, which show that 24% of deaths were seemingly potentially survivable and 90% of them were related to hemorrhage. Among the injuries that caused death, 67.3% were truncal, 19.2% were junctional (neck, axilla, and inguinal regions), and 13.5% were located on the extremities.

[1,2] This data reveals the paramount importance of hemor-

Address for correspondence: H. Erhan Güven, M.D. Sağlık Bilimleri Üniversitesi Gülhane Gülhane Eğitim ve Araştırma Hasanesi, Genel Cerrahi Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 304 20 06 E-mail: drerhanguven@gmail.com Submitted: 22.09.2017 Accepted: 26.09.2017

Ulus Travma Acil Cerrahi Derg 2017;23(5):357–361 doi: 10.5505/tjtes.2017.47279 Copyright 2017 TJTES

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rhage control to save lives with proper scientific and technical measures. Topically applied hemostatic agents mainly aim to help those with junctional hemorrhage because they are not suitable for tourniquet application, such as extremity wounds. However, they can also be used along with tourniquets in extremity wounds.

In a review by Sobrino et al., it is stated that the consequences of trauma in a civilian setting are fundamentally the same.

Hemorrhage is the second leading cause of death after traumatic brain injury in immediate and early phases of trauma.[3] With increasing occurrence of terrorist attacks globally, it will not be surprising to experience a constant rise in exsanguination incidence among civilian mass casualties.

Moreover, one should always keep in mind that in the battlefield, rural areas, and wilderness, the so called pre-hospital setting, the first responder to hemorrhage is almost always a non-medical personnel: a friend (so called a “buddy”) on the battlefield, a local resident, or a companion. Thus, the first intervention should be called an “attempt to control bleeding” rather than “hemostasis.”

Topical hemostatics are also important for trauma victims who can make it to a medical facility. Intracorporeal topical hemostatics are used in emergency surgery for trauma, such as to control initial damage and stop bleeding from liver or major vessels. Although some agents mentioned below have also been used for intracorporeal hemostasis with great success, the evaluation criteria of topical hemostatic agents are different from this paper’s vantage point.

357

Güven. Topical hemostatics for bleeding control in pre-hospital setting: Then and now

Physiological Hemostasis Let me provide some information on clot formation prior to the discussion on hemostasis. One of the most dynamic system of concurrent production (clotting) and destruction (fibrinolysis) in vivo is the coagulation system. The basic concept of coagulation has not changed after the introduction of the “cascade” system by MacFarlane in 1964.[4] Reflex vasoconstriction occurs first under the influence of local mediators. Von Willebrand factor and glycoproteins lock each other to start thrombocyte adhesion. Secretion continues from the thrombocytes leading to further adhesion and aggregation. Activated by subendothelial tissue factor, the extrinsic pathway proceeds to convert factor X to its active form. Factor XII triggers another route, intrinsic pathway that ends up at the same step where active factor X is formed.

The common pathway moves forward to the final destination where a stable clot is formed. Homeostasis of hemostasis continues with the fibrinolytic events that terminate the clot after it is no longer needed.[5]

Topical Hemostatic Agents With this proximate knowledge about the clotting process, it is practical to classify topical hemostatics according to their action mechanism into three categories: 1) Coagulation factor and thrombocyte concentrators 2) Mucoadhesive agents or physical sealants 3) Coagulation cascade activators that either supply some key proteins of the system or trigger the system

Zeolite As an easy-to-find natural mineral, zeolite can be considered as the prototype of concentrator agents. Its porous structure allows rapid adsorption of water, which increases the relative concentration of coagulation factors and thrombocytes at the bleeding site where clotting process takes place. Adsorption is an exothermic reaction that gives off heat.

In a study with zeolite’s early commercial form, QuikClot® bleeding was controlled in 92% of patients. However, the heat generated during the application caused pain in one-fourth of the patients and three burns were encountered (Table 1).[6] Aiming to reduce the heat effect of zeolite, QuikClot ACS® was introduced in the market. In their animal model study, Eryilmaz et al. concluded that QuikClot ACS® decreased the amount of bleeding but could not completely stop it in any of the test subject. Furthermore, they observed cellular changes caused by heat generation reaching up to 80°C.[7] The successor of these two products was QuikClot ACS+®.

Hydrated zeolites were packed in porous meshes to minimize heat problem. This was accomplished at a cost of decreased hemostatic efficacy, discrediting the product for combat scenarios.[8,9] Clinoptilolite, a type of zeolite mineral, was tested for the first time by Bayır et al. and was found to be as effective as 358

kaolin, which will be discussed below, without inducing any temperature rise.[10] New research on other zeolite minerals should be encouraged as zeolite-based topical hemostatics are easy to produce with low cost.

Starch Derivatives Belonging to this group, TraumaDex® contains microporous polysaccharide hemospheres and BleedArrest® contains amylopectin. Both are derived from potato starch and are found to be successful concentrators but are not applicable on battlefields.[11]

Chitosan Chitin is the main polysaccharide found in the exoskeleton of invertebrates and shells of crustaceans (such as crab, shrimp, lobster, etc.). Chitosan is produced by the deacetylation of chitin and is the center of attraction for a series of biomedical investigations on obesity, fungal infestations, and bacterial infections, as well as hemorrhage.[12,13] Chitosan’s positively charged surface successfully attracts erythrocytes and mechanically seals the bleeding site, and its chemical structure causes vasoconstriction, which enhances its hemostatic effect.[14,15] HemCon Bandage®, Celox®, and ChitoGauze® are the best known commercial products containing chitosan as an active ingredient. Preclinical studies are the mainstay of using chitosan-based materials on the battlefield.[16] It achieves hemostasis without requiring the integrity of the clotting system and without any heat problems in the tissue.[8,16] Wedmore’s study on 64 wounded soldiers reported that HemCon® was successful in stopping or reducing the bleeding (Table 1).[17] Additional case reports and animal studies with Celox® and ChitoGauze® supported the former outcomes, and all the abovementioned products took their places in the guideline of the Committee on Tactical Combat Casualty Care (CoTCCC).[18] A novel chitosan-based hemostatic product was introduced in 2014 and acquired U.S. Food and Drug Administration (FDA) approval. XStat® became the prototype of a new class of topical hemostatic agent/device: a non-absorbable, expandable, hemostatic sponge for internal use.[19] The syringelike device consists of chitosan-coated mini-sponges that expand in contact with blood. It concentrates clotting factors and seals the bleeding site at the same time. Although not yet cleared for use above the clavicle line, in the thorax, and in the abdomen, this device is designed to help bleeding control in wounds with a narrow opening in junctional body parts and extremities. Its application is also restricted to patients who are expected to reach proper surgical care facility in no more than 4 hours.[20]

Kaolin Kaolin is a clay rock that is rich in kaolinite. It has a polar surface with a slight negative charge that plays a key role in triggering the intrinsic pathway of the coagulation cascade, Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Güven. Topical hemostatics for bleeding control in pre-hospital setting: Then and now

Table 1. Three human studies on three commonly used topical hemostatic agents Study

Topical Number hemostatic of patients agent (n)

Wound localization

Results

Head, scalp, and neck (n=12)

Overall efficacy rate, 92%

Extremities (n=61)

Efficacy in blast trauma, 21/22

Chest and upper back (n=16)

Efficacy in gunshot wounds, 65/68

Abdomen, lower back, and groin (n=18)

Efficacy in stab wounds, 3/5

Intracorporeal (n=20)

Mild-to-severe discomfort due to

Rhee et al.[6]

Quikclot

(zeolite)

103

heat produced by the material.

Three burn cases, one requiring

skin grafting

One foreign body reaction and scar

formation (in intracorporeal use)

Wedmore et al.

HemCon

(chitosan)

Extremities (n=35)

Success rate, 97%

Head and neck (n=4)

No complications or adverse

Others (n=25)

events reported

Ran et al.[22]

Extremities (n=4)

Overall success rate, 79%

Others (head, neck, axilla, abdomen,

No complications or adverse

etc.) (n=10)

events reported

[17]

Quikclot Combat

64

14

Gauze (kaolin)

making it a member of the procoagulant class topical hemostatics. It is likely that kaolin acts by augmenting activation of factors XII and XI, as well as prekallikrein and high-molecular-weight kininogen.[8,21] Recommended by CoTCCC since 2008, QuikClot Combat Gauze® was approved by FDA in 2013 for external use. Although the only study conducted on the field with soldiers by Ran et al. showed an efficacy of 79%, after some animal studies, CoTCCC was confident that this product should be used in the first line of bleeding control attempt (Table 1).[22–24] The late onset of hemostatic effect and the need for an intact coagulation system without any factor deficiencies are the pitfalls of kaolin-based hemostatics.[8]

Smectite Woundstat®, a commercial product containing smectite group clay, which has the ability to stop bleeding by simultaneously concentrating the clotting factors, initiating the intrinsic pathway, and sealing the wound, was cleared by FDA in 2007.[8,25] When compared with others, it has proved its superiority as being the fastest and most effective product in animal studies.[26,27] However, it induces transmural damage to the bleeding vessel, making it impossible to perform repair, and causes occluding thrombosis to the distal of the injury that compromises safety.[28] In general, removal of a topical hemostatic during a definitive surgical intervention of hemorrhage, especially when it is in the granular form, has paramount importance. However, as an inert material, Woundstat® was reported to adhere so tightly to the applied tissue that several attempts were needed for a complete removal.[27] Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Because of these safety issues, it was permanently suspended

by FDA in 2009. Woundstat® is a good example for “too good to be true” situation after all.

Herbal Complex Urtica dioica, Vitis vinifera, Glycrrhiza glabra, Alpinia officinarum, and Thymus vulgaris are the ingredients of Ankaferd Bloodstopper®. Its action mechanism is described in its information brochure. It acts independently from the clotting system via erythrocyte aggregation in a protein network environment. Pubmed search revealed few review studies mainly commenting on its efficacy during endoscopic interventions.

[29–31] Recent studies on this product focus on growth inhibitory properties, germicidal effects against hydatid cyst, and acceleration of muscle healing in open fractures rather than its hemostatic activity.[32–34]

Dry Fibrin Sealant Dressing This includes a subgroup of procoagulants as a supplier of clotting factors. It contains purified fibrinogen, thrombin, and factor XIII, as well as factor IV (calcium). Although it was found to be successful in its initial use on the battlefield, its cost and efficacy of cheaper products blocked its path.[14,27] Topical hemostatics are always a focus of interest for research and development staff and scientists. New materials, such as polyurethane foam and hydrophobically modified alginate lyophilized sponge, as well as modification of the existing ones, such as two-layer gelatin, are under continuous 359

Güven. Topical hemostatics for bleeding control in pre-hospital setting: Then and now

investigations that will surely contribute to the war against war injuries.[35–38]

DISCUSSION An ideal topical hemostatic agent to be used on a battlefield should be non-toxic, be able to control both arterial and venous hemorrhage, be ready to be used instantly, be easily applicable by the sufferer or a buddy, have a long shelf-life with copper-bottomed protection, be small in size and weight but durable in all extreme conditions in a haversack, be inexpensive and cost-effective, and perhaps be practical under night vision.[39,40] It is equally important to develop topical hemostatics and quantify the comparison between them. A recent study proposes a novel methodology, which is in line with FDA’s clinician-reported scale. If used, this validated bleeding severity scale will assure that all clinicians conducting studies on topical hemostatics are speaking the same language when it comes to comparing outcomes.[41] Zeolite-based agents are most effective in their purest mineral form, but heat production is a major problem to limit their use. Hydration of the material reduces this side effect but it also compromised its efficacy.[6,8,9] Although very successful in achieving bleeding control, smectite is outdated because of its potential for tissue damage and inability to wipe it off the tissue.[15,27] Chitosan seems relatively safe; the only concern regarding its use may be shellfish allergy of the individual.

[14,15] Kaolin is also safe but needs more time for achieving hemostasis and an intact coagulation system in the individual.

[8] Dry fibrin sealants are expensive and fragile for battlefield environment.[14] At this juncture, the latest revision of coTCCC Guidelines for Medical Personnel (April 16, 2017) advocates a kaolin-based agent in the first line and chitosan-based agents afterward to be used in conjunction with appropriate tourniquets.[42]

Acknowledgments I cordially thank Mehmet Eryılmaz, M.D., for his support. I also thank the chairman and board members of the Turkish Association of Trauma and Emergency Surgery for their kind invitation for this paper. This work is derived from the original speech given by the author in the War Surgery session of the 11th Turkish Congress of Trauma and Emergency Surgery held in April 2017.

Conflict of Interest I do not have any financial or non-financial interest, membership, employment, consultancies, stock ownership, or patentlicensing arrangements in any of the products mentioned in this paper. The trademark names of products are used because all papers regarding topical hemostatic also mention them.

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9. Kheirabadi BS, Edens JW, Terrazas IB, Estep JS, Klemcke HG, Dubick MA, et al. Comparison of new hemostatic granules/powders with currently deployed hemostatic products in a lethal model of extremity arterial hemorrhage in swine. J Trauma 2009;66:316–26.

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11. Burgert J, Gegel B, Neal AR, Kammer KE, Paul ME, Schwartz DJ, et al.

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12. Jull AB, Ni Mhurchu C, Bennett DA, Dunshea-Mooij CA, Rodgers A. Chitosan for overweight or obesity. Cochrane Database Syst Rev 2008:CD003892.

13. Verlee A, Mincke S, Stevens CV. Recent developments in antibacterial and antifungal chitosan and its derivatives. Carbohydr Polym 2017;164:268–83.

14. Achneck HE, Sileshi B, Jamiolkowski RM, Albala DM, Shapiro ML, Lawson JH. A comprehensive review of topical hemostatic agents: efficacy and recommendations for use. Ann Surg 2010;251:217–28.

15. Smith AH, Laird C, Porter K, Bloch M. Haemostatic dressings in prehospital care. Emerg Med J 2013;30:784–9.

16. Bennett BL, Littlejohn L. Review of new topical hemostatic dressings for combat casualty care. Mil Med 2014;179:497–514.

17. Wedmore I, McManus JG, Pusateri AE, Holcomb JB. A special report on the chitosan-based hemostatic dressing: experience in current combat operations. J Trauma 2006;60:655–8.

18. Bennett BL. Bleeding Control Using Hemostatic Dressings: Lessons Learned. Wilderness Environ Med 2017;28:S39–49.

19. De Novo Classification Request For Xstat. Available at: https://www. accessdata.fda.gov/cdrh_docs/reviews/K130218.pdf. Accessed Apr 16, 2017.

20. Sims K, Montgomery HR, Dituro P, Kheirabadi BS, Butler FK. Management of External Hemorrhage in Tactical Combat Casualty Care: The Adjunctive Use of XStat™ Compressed Hemostatic Sponges: TCCC Guidelines Change 15-03. J Spec Oper Med 2016;16:19–28.

21. Gordy SD, Rhee P, Schreiber MA. Military applications of novel hemo-

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23. Kheirabadi BS, Scherer MR, Estep JS, Dubick MA, Holcomb JB. Determination of efficacy of new hemostatic dressings in a model of extremity arterial hemorrhage in swine. J Trauma 2009;67:450–9.

24. Rall JM, Cox JM, Songer AG, Cestero RF, Ross JD. Comparison of novel hemostatic dressings with QuikClot combat gauze in a standardized swine model of uncontrolled hemorrhage. J Trauma Acute Care Surg 2013;75:S150–6.

25. Zhang YJ, Gao B, Liu XW. Topical and effective hemostatic medicines in the battlefield. Int J Clin Exp Med 2015;8:10–9.

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27. Ward KR, Tiba MH, Holbert WH, Blocher CR, Draucker GT, Proffitt EK, et al. Comparison of a new hemostatic agent to current combat hemostatic agents in a Swine model of lethal extremity arterial hemorrhage.

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29. Chen YI, Barkun AN. Hemostatic Powders in Gastrointestinal Bleeding: A Systematic Review. Gastrointest Endosc Clin N Am 2015;25:535–52.

30. Barkun AN, Moosavi S, Martel M. Topical hemostatic agents: a systematic review with particular emphasis on endoscopic application in GI bleeding. Gastrointest Endosc 2013;77:692–700.

31. ASGE Technology Committee, Wong Kee Song LM, Banerjee S, Barth BA, Bhat Y, Desilets D, Gottlieb KT, et al. Emerging technologies for endoscopic hemostasis. Gastrointest Endosc 2012;75:933–7.

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Growth inhibitory activity of Ankaferd hemostat on primary melanoma cells and cell lines. SAGE Open Med 2017;5:2050312116689519.

33. Uygun M, Yavuz OY, Uraş İ, Duman İG, Haltaş H, Kömürcü M. Effect of Ankaferd Blood Stopper on muscle healing. Clin Invest Med 2016;39:27526.

34. Metin B, Yilmaz N, Beyhan YE, Babür C, Sipahi M, Ede H, et al. In Vitro Efficacy of the Ankaferd Galenic Hemostatic Extract as a Germicidal Agent. Iran J Parasitol 2016;11:406–10.

35. Howe N, Cherpelis B. Obtaining rapid and effective hemostasis: Part I. Update and review of topical hemostatic agents. J Am Acad Dermatol 2013;69:659.e1–659.e17.

36. Takagi T, Tsujimoto H, Torii H, Ozamoto Y, Hagiwara A. Two-layer sheet of gelatin: A new topical hemostatic agent. Asian J Surg 2016. pii: S1015-9584(16)30118–X. 37. Dowling MB, Chaturvedi A, MacIntire IC, Javvaji V, Gustin J, Raghavan SR, et al. Determination of efficacy of a novel alginate dressing in a lethal arterial injury model in swine. Injury 2016;47:2105–9.

38. Broekema FI, van Oeveren W, Boerendonk A, Sharma PK, Bos RR. Hemostatic action of polyurethane foam with 55% polyethylene glycol compared to collagen and gelatin. Biomed Mater Eng 2016;27:149–59.

39. Pusateri AE, McCarthy SJ, Gregory KW, Harris RA, Cardenas L, McManus AT, et al. Effect of a chitosan-based hemostatic dressing on blood loss and survival in a model of severe venous hemorrhage and hepatic injury in swine. J Trauma 2003;54:177–82.

40. Kheirabadi B. Evaluation of topical hemostatic agents for combat wound treatment. US Army Med Dep J 2011:25–37.

41. Lewis KM, Li Q, Jones DS, Corrales JD, Du H, Spiess PE, et al. Development and validation of an intraoperative bleeding severity scale for use in clinical studies of hemostatic agents. Surgery 2017;161:771–81.

42. TCCC Guidelines for Medical Personnel. Available at: http://cotccc. com/wp-content/uploads/TCCC-Guidelines-for-Medical-Personnel-170131.pdf. Accessed Apr 16, 2017.

DERLEME - ÖZET

Kanamalara hastane öncesi müdahale sırasında kullanılan topikal hemostatikler: Öncesi ve şimdi Dr. H. Erhan Güven Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Ankara

Kanama sadece yol açtığı volüm defisitine bağlı olarak ölüme neden olan bir sorun değildir. Neden olduğu düzeltilemeyen hipotermi, metabolik asidoz ve koagülasyon bozukluklarıyla da hastaneye yetiştirebilmiş olsa bile yaralının kaybına neden olabilir. Travmaya bağlı olarak boyun, koltuk altı ve kasık bölgeleri gibi turnikeye uygun olmayan lokalizasyonlarda ve ekstremitelerde görülen dışa kanamaların saha şartlarında etkin bir şekilde kontrol altına alınması amacıyla geliştirilen birçok topikal hemostatik ajan mevcuttur. Bu yazıda, farklı etki mekanizmaları ve etkinlikleri olan bu ajanların saha kullanımına uygun olanları ve konu üzerindeki son öneriler irdelenmiştir.

Anahtar sözcükler: Hastane öncesi; kanama; topikal hemostatik.

Ulus Travma Acil Cerrahi Derg 2017;23(5):357–361

doi: 10.5505/tjtes.2017.47279

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EXPERIMENTAL STUDY

Evaluation of different treatment protocols for combined injury-induced lung injury in rabbits Xiao Bing Li, M.D. Department of Burn and Plastic Surgery, Tianjin First Center Hospital, Tianjin-PR China

ABSTRACT BACKGROUND: This study aims to evaluate the effectiveness of different treatment regimens on combined injury-induced lung injury.

METHODS: Rabbits were subjected to non-lethal closed-chest bilateral lung contusion followed by a 30% total body surface area scald burn. The rabbits were randomly assigned to resuscitation groups that maintained a minimum mean arterial blood pressure of 70 mmHg using one of the following three methods: normal saline plus polygeline injection in a ratio of 1:1 (1:1G), normal saline plus polygeline injection in a ratio of 1:2 (1:2G), and normal saline plus polygeline injection in a ratio of 1:3 (1:3G), After injury, lung injury was assessed using lung wet-to-dry (W/D) weight ratio, enzyme-linked immunosorbent assay, and real-time PCR. RESULTS: In the 1:3 fluid resuscitation group, rabbits exhibited significantly reduced lung W/D ratio, alveolar hemorrhage, myeloperoxidase activity, and IL-8 and TNF-α levels in the serum compared with the 1:1 or 1:2 fluid resuscitation groups. The 1:3 fluid resuscitation-treated rabbits also attenuated ultrastructural changes in the lung 24 h after the combined injury.

CONCLUSION: This study demonstrated the impact of fluid resuscitation on combined injury-induced lung injury. Further, 1:3 fluid resuscitation treatment at the early stage of lung injury after combined lung contusion and burn injury was found to be more effective.

Keywords: Acute lung injury; burn injury; fluid resuscitation; lung contusion.

INTRODUCTION Combined lung contusion (LC) and burn injuries increases morbidity and mortality by promoting severe lung injury and hemodynamic shock.[1–3] Burn injury alone, even in the absence of smoke inhalation, often causes damage to the lung tissue.[4] In recent years, increasing evidence has suggested that neutrophils play an important role in the pathophysiology of burn-induced lung injury.[5,6] LC is associated with acute respiratory failure, exhibiting as clinical acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).[7,8] Proper fluid resuscitation is critical for the survival of the Address for correspondence: Xiao Bing Li, M.D. Department of Burn and Plastic Surgery, Tianjin First Center Hospital, Tianjin 300192, China Tel: +86 22 23626258 E-mail: fzhwy1981@163.com Submitted: 04.05.2015 Accepted: 20.10.2016

Ulus Travma Acil Cerrahi Derg 2017;23(5):362–367 doi: 10.5505/tjtes.2017.21736 Copyright 2017 TJTES

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victim of a major burn injury.[9,10] With adoption of weight and injury size-based formulas for resuscitation, multiple organ dysfunctions and inadequate resuscitation have become uncommon. However, LC is sensitive to fluid resuscitation after trauma. Such treatment can increase the lung water content and lead to desaturation.[11] The decision to use colloid or crystalloid solutions for fluid resuscitation of critically ill patients remains controversial.

In the light of these findings, we hypothesized that fluid resuscitation can provide protection against combined LC and burn injury-induced pulmonary damage. We aimed to investigate whether and to what extent fluid resuscitation reduces this damage by determining the presence of oxidative tissue injury using biochemical and histological parameters.

MATERIALS AND METHODS Animals Eighty healthy adult male New-Zealand rabbits weighing between 3.1 and 3.3 kg were used for all experiments. Rabbits were housed in microisolator cages under specific pathogenfree conditions. All animal experiments were approved by the Institutional Animal Care and Use Committees at first center hospital.

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Li. Evaluation of different treatment protocols for combined injury-induced lung injury in rabbits

Combined Lung Contusion and Burn Injury

Total RNA Extraction and Real-Time PCR

Rabbits were anesthetized with 50 mg/kg intramuscular ketamine hydrochloride. Each rabbit’s right hemithorax was drawn, and a 350-g metal cylinder was dropped from a height of 150 cm in the supine position, as described in the study by Raghavendran et al.[12] Trauma was standardized by applying 5.14 J of energy on the chest region according to the formula.

The impact energy (E) of the falling weight was calculated using the following equation: E = m (0.35 kg) × g (9.8 m/s2) ×h (150 cm).[13]

Total RNA was isolated from the lung samples using a QIAGEN RNeasy Mini Kit (Dusseldorf, Germany) and treated with RNase-free DNase. RNA was reverse transcribed, and cDNA was subjected to PCR for analyzing the expression of IL-8 and TNF-α. IL-8 sense, 5′-CAA ACC TTTCCA CCC CAA AT-3′ and IL-8 anti-sense, 5′-ATT GCATCT GGC AAC CCT AC-3′, amplified fragment length 572 bp; and TNF-α sense, 5′-TTATCT CTC AGC TCC ACG CC-3′ and TNF-α anti-sense, 5′-TGC GCA CTG AAA GCA TGA TC-3′, amplified fragment length 383 bp.

Rabbits subjected to combined injury were subjected to LC, followed by induction of 30% TBSA full-thickness burns on the back with 90°C water for 9 s.

The rabbits were randomly assigned to resuscitation groups that maintained a minimum mean arterial blood pressure of 70 mmHg using one of the following three methods: normal saline plus polygeline injection in a ratio of 1:1 (1:1G) (n=20), normal saline plus polygeline injection in a ratio of 1:2 (1:2G) (n = 20), normal saline plus polygeline injection in a ratio of 1:3 (1:3G) (n=20), and control rabbits which were anesthetized, but were not injured and did not receive treatment (n=20).

Lung Histopathology The lung was excised and perfused with 10% PBS buffered formalin. After fixation, lung tissues were embedded with paraffin and sectioned (5 um sections). The sections were stained with hematoxylin & eosin.

Electron Microscopy Lung tissues were post-fixed in 1% osmium tetroxide in sodium phosphate buffer and then processed and embedded in epoxy resin. Thin sections were installed on copper grids and observed on a transmission electron microscope (TEM).[14]

RESULTS Fluid Resuscitation Reduces Pulmonary Edema Induced By Combined Injury Pulmonary edema is one of the most characteristic pathologic changes in burn-induced lung injury.[15] Meanwhile, LC leads to hypoxemia severe enough to qualify as ALI/ARDS. The lung W/D ratio was examined to determine the effect of combined injury on pulmonary edema. As shown in Figure 1, the lung W/D ratio in 1:3 fluid resuscitation-treated rabbits was substantially higher than that in the control group (p<0.05) and lower than that in the 1:2 fluid resuscitation group. The lung W/D ratio in the 1:2 fluid resuscitation group was lower than that in the 1:1 fluid resuscitation group (p<0.05), which suggests that pulmonary edema alleviated when rabbits with combined injury were treated with fluid resuscitation.

Fluid Resuscitation Protects Against Histopathologic Changes Induced

By Combined Injury As illustrated in Figure 2b, c, the lungs in rabbits with combined injury show apparent proinflammatory changes charac6

Lung samples were separated and weighed immediately after removal to determine the wet weight. The sample was ovendried at 65°C for 24 h and re-weighed. The lung wet-to-dry weight ratio was calculated as the index of lung water content.

Measurement of Myeloperoxidase (MPO) Activity Lungs of the rabbits from all groups were separated and homogenized. The homogenates were used to observe MPO activity. Briefly, weighed lungs were thawed and homogenized in a homogenate medium. The homogenates were then performed according to the manufacturer’s instructions.

Measurement of Cytokine Levels in the Serum TNF-α and IL-8 serum levels in the rabbits were measured by enzyme-linked immunosorbent assay (ELISA), according to the manufacturer’s instructions (R&D Systems, Minneapolis, MN).

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Wet-Dry Weight Ratio

Wet/Dry Weight Determinations

1:1G 1:2G 1:3G CG

4 *#&

*#&

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0

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Figure 1. The wet/dry ratio of the lung for each group. The wet/ dry ratio of the lung was measured for the four groups of rabbits: control group, 1:1 fluid resuscitation group, 1:2 fluid resuscitation group, and 1:3 fluid resuscitation group. (Data are denoted as means±s.e.m. n=10 rabbits per group,*p<0.05 compared with CG. # p<0.05 compared with 1:1G. &p<0.05 compared with 1:2G. CG: Control group, 1:1G: 1:1 fluid resuscitation group, 1:2G: 1:1 fluid resuscitation group, and 1:3G: 1:1 fluid resuscitation group).

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Li. Evaluation of different treatment protocols for combined injury-induced lung injury in rabbits

(a)

(b)

(c)

(d)

Figure 2. Histological evaluation of fluid resuscitation-treated rabbits following combined injury.

These images are representative of the treatment groups at 24 h post injury. (a) control group, (b) 1:1 fluid resuscitation group, (c) 1:2 fluid resuscitation group, and (d) 1:3 fluid resuscitation group.

(H&E staining Ă&#x2014;200) (n=10 rabbits per group, CG: control group, 1:1G: 1:1 fluid resuscitation group, 1:2G: 1:1 fluid resuscitation group, and 1:3G: 1:1 fluid resuscitation group).

terized by lung edema, alveolar hemorrhage and neutrophil infiltration, and destruction of the epithelial and endothelial cell structure. Furthermore, 1:3 fluid resuscitation-treated rabbits

showed significant alleviation of interstitial edema formation at 24 h (Fig. 2d). Conversely, no destructive changes were observed in lung tissues from the control group (Fig. 2a).

(a)

(b)

(c)

(d)

Figure 3. Electron microscopic findings of the lamellar body. (a) Electron micrograph of the lungs of the control animal that did not have an injury and did not receive any treatment. (b) TEM image of the lamellar body in the 1:1 fluid resuscitation group at 24 h after injury. (c) TEM image of the lamellar body in the 1:2 fluid resuscitation group at 24 h after injury. (d) TEM image of the lamellar body in the 1:3 fluid resuscitation group at 24 h after injury. (n=10 rabbits per group, CG: control group, 1:1G: 1:1 fluid resuscitation group, 1:2G: 1:1 fluid resuscitation group, and 1:3G: 1:1 fluid resuscitation group).

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MPO activity (U/g tissue)

5

1:1G 1:2G 1:3G CG

4 *#&

3

*#&

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Ultrastructural Changes in Combined InjuryInduced Lung Injury Compared With Controls The degree of lung injury was further observed by TEM examination of the different experimental groups. TEM exhibited that the control group had a normal lung tissue structure.

Compared with other groups, we identified lamellar bodies with few cavitations in the 1:3 fluid resuscitation group (Fig. 3).

1

Lung MPO Activity in Lung Injury 0 24h

48h

Figure 4. The MPO activity in lung homogenates. Fluid resuscitation inhibits myeloperoxidase (MPO) activity in combined injury-induced ALI. After 24 and 48 h interventions, rabbits were sacrificed, and their lungs were removed. The MPO activity was measured to assess the accumulation and activation of neutrophils in the lung tissues. (Data are denoted as means±s.e.m, n=10 rabbits per group, *p<0.05 compared with CG. #p<0.05 compared with 1:1G. & p<0.05 compared with 1:2G. CG: control group, 1:1G: 1:1 fluid resuscitation group, 1:2G: 1:1 fluid resuscitation group, and 1:3G: 1:1 fluid resuscitation group).

400

1:1G 1:2G 1:3G CG *#&

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20

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15 TNF-a (pg/mL)

IL-8 (pg/mL)

(a)

Neutrophil accumulation in the lungs was determined suing MPO activity assays.[16] MPO expression was markedly upregulated in fluid resuscitation-treated rabbits (Figure 4). This increase in MPO levels was clearly weakened in 1:3 fluid resuscitation-treated rabbits and differed obviously from that in MPO levels in 1:1 or 1:2 fluid resuscitation treatment after injury (p<0.05) (Figure 4). MPO estimates in the control group and at 24 and 72 h after combined injury were significantly diverse from those at all other time points in both groups (p<0.05) (Figure 4).

*#&

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IL-8 mRNA

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40

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1:1G 1:2G 1:3G CG

80 TNF-a mRNA

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60 40

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0 24h

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Figure 5. Effects of fluid resuscitation on inflammatory cytokine expression in combined injury-induced ALI rabbits. Serum and lung samples were obtained 24 or 48 h after combined injury to analyze inflammatory cytokine, including IL-8 (A), TNFα(B), IL-8 mRNA (C), and TNF-α mRNA (D), levels. (Data are denoted as means±s.e.m, n=10 rabbits per group, *p<0.05 compared with CG. #p<0.05 compared with 1:1G. and &p<0.05 compared with 1:2G. CG: control group, 1:1G: 1:1 fluid resuscitation group, 1:2G: 1:1 fluid resuscitation group, and 1:3G: 1:1 fluid resuscitation group).

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Fluid Resuscitation Decreases Local and Systemic Inflammatory Mediator Levels Induced

By Combined Injury Inflammatory mediators play an important role in the pathogenesis of burn-induced ALI.[17] TNF-α and IL-8 levels in the serum were determined by ELISA. Combined injury showed elevated TNF-a and IL-8 levels in the serum in 1:1 and 1:2 fluid resuscitation-treated rabbits. 1:3 fluid resuscitation treatment lowered these mediator levels in the blood (Figure 5a, b). In line with the measurements of the serum, 1:3 fluid resuscitation-treated rabbits had substantially lower TNF-α mRNA and IL-8 mRNA expression levels in the lungs (Figure c, d).

Statistical Analyses We used Student’s t-test for comparing differences between groups. P<0.05 was considered to be statistically significant.

Data are expressed as mean±standard error of the mean (s.e.m.).

DISCUSSION We were able to demonstrate a reduction in the severity of combined injury-induced lung injury in 1:3 fluid resuscitationtreated rabbits. 1:3 fluid resuscitation-treated rabbits with combined injury exhibited lower pulmonary edema, alveolar hemorrhage, and neutrophil invasion after injury. The generation of proinflammatory mediators, IL-8 and TNF-a, was markedly downregulated in the 1:3 fluid resuscitation group.

Under conditions of combined injury, we also demonstrated lower neutrophil recruitment in the lung.

Fluid resuscitation following burn injury must support organ perfusion with the least amount of fluid necessary and the least physiological cost.[18] Resuscitation fluids are broadly categorized into colloid and crystalloid solutions. However, it is unclear whether fluid resuscitation is closely associated with combined injury. To the best of our knowledge, this study was the first to compare strategies for fluid resuscitation after combined injury in rabbits over a midterm period of 48 h with histopathology and pathophysiology. Our results suggest that fluid resuscitation attenuates lung injury in rabbits after combined injury. This is supported by three findings. First, colloids are more effective than crystalloids in early resuscitation of patients in shock when administered during surgery.[19] Our data showed that 1:1 fluid resuscitation-treated rabbits had obviously elevated congested alveolar capillaries, hemorrhage, and some alveolar wall thickening compared with 1:3 fluid resuscitation-treated rabbits after injury (Figure 2).

Type II alveolar epithelial cells proliferate to cover the injured basement membrane and differentiate into type I alveolar epithelial cells.[20] Further, lighter ultrastructural changes were observed by TEM after 24 h in 1:3 fluid resuscitation-treated rabbits after combined injury. Second, a major hallmark of ALI is the intrapulmonary invasion of neutrophils.[21] The nor366

mal response to pulmonary infection or injury induces the controlled recruitment of neutrophils to the lung, which are then rapidly eliminated through the induction of apoptosis and subsequent clearance by alveolar macrophages during the resolution phase of the inflammatory response.[22] Our data are in agreement with these findings. However, we showed that an increase in the MPO activity was clearly diminished in 1:3 fluid resuscitation-treated rabbits and significantly differed from that in 1:1 and 1:2 fluid resuscitation-treated rabbits at 24 or 48 h. Third, patients with ALI/ARDS had persistent elevations in inflammatory cytokines (TNF-α, IL-1β, and IL6) levels in the plasma, hypothalamic-pituitary-adrenal axis hormones, and similar severity of organ dysfunction scores.

[23] Colloids have a possible advantage over crystalloids when used for initial hemodynamic stabilization of critically ill patients.[24] Similarly, 1:1 fluid resuscitation treatment increased the release of IL-8 (Figure 5a) and TNF-α (Figure 5b) in the lung compared with 1:3 fluid resuscitation treatment. In the air space, an alveloar macrophage secretes cytokines, IL-8 and TNF-α, which act locally to stimulate chemotaxis and activate neutrophis.[25] Our research also shows that IL-8 and TNF-α levels were significantly affected at 24 h post injury in the 1:3 fluid resuscitation group compared with those in the 1:1 fluid resuscitation group (Figure 5c, d). Collectively, these findings suggest that fluid resuscitation significantly attenuates lung injury in rabbit. In conclusion, we were able to show that after combined injury, 1:3 fluid resuscitation-treated animals develop a less severe lung injury than different fluid resuscitation-treated animals. Further studies are needed to better understand the effects of fluid resuscitation on both neutrophil development and function in pulmonary inflammation.

Acknowledgments We are grateful to Xueqin Zheng, Qianqian Zhang, Peng Yu, and Wanying Xia for technical assistance. This study was supported by the science and technology fund of Tianjin municipal health bureau (2012KZ020).

Conflict of interest: None declared.

REFERENCES 1. Baker TA, Romero J, Bach HH 4th, Strom JA, Gamelli RL, Majetschak M. Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage. Crit Care Med 2012;40:876–85.

2. Busche MN, Gohritz A, Seifert S, Herold C, Ipaktchi R, Knobloch K, et al. Trauma mechanisms, patterns of injury, and outcomes in a retrospective study of 71 burns from civil gas explosions. J Trauma 2010;69:928– 33.

3. Shuker ST. Facial skin-mucosal biodynamic blast injuries and management. J Oral Maxillofac Surg 2010;68:1818–25.

4. Richard F. Oppeltz, Meenakshi Rani, Qiong Zhang, Martin G. Schwacha. Burn-induced alterations in toll-like receptor-mediated responses by bronchoalveolar lavage cells. Cytokine 2011;55:396–401.

5. Skoge M, Wong E, Hamza B, Bae A, Martel J, Kataria R, et al. A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells. PLoS One 2016;11:e0154491.

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7. Kalbitz M, Karbach M, Braumueller S, Kellermann P, Gebhard F, Huber-Lang M, et al. Role of Complement C5 in Experimental Blunt Chest Trauma-Induced Septic Acute Lung Injury (ALI). PLoS One 2016;11:e0159417.

8. Bakan V, Kurutaş EB, Çıralık H, Gül M, Çelik A. Endogenous erythropoietin level and effects of exogenous erythropoietin in a rat model of blunt chest trauma-induced pulmonary contusion. Ulus Travma Acil Cerrahi Derg 2016;22:322–7.

9. Peeters Y, Lebeer M, Wise R, Malbrain ML1. An overview on fluid resuscitation and resuscitation endpoints in burns: Past, present and future. Part 2 - avoiding complications by using the right endpoints with a new personalized protocolized approach. Anaesthesiol Intensive Ther 2015;47:15–26.

10. Guilabert P, Usúa G, Martín N, Abarca L, Barret JP, Colomina MJ. Fluid resuscitation management in patients with burns: update. Br J Anaesth 2016;117:284–96.

11. Prunet B, Prat N, Couret D, Cordier PY, De Bourmont S, Lambert D, et al. Midterm effects of fluid resuscitation strategies in an experimental model of lung contusion and hemorrhagic shock. Shock 2014;41:159–65.

12. 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.

13. Cohn SM, Dubose JJ. Pulmonary contusion: an update on recent advances in clinical management. World J Surg 2010;34:1959–70.

14. Ryman-Rasmussen JP, Cesta MF, Brody AR, Shipley-Phillips JK, Everitt JI, Tewksbury EW, et al. Inhaled carbon nanotubes reach the subpleural tissue in mice. Nat Nanotechnol 2009;4:747–51.

15. Tian KY, Liu XJ, Xu JD, Deng LJ, Wang G. Propofol inhibits burn injury-induced hyperpermeability through an apoptotic signal pathway in

microvascular endothelial cells. Braz J Med Biol Res 2015;48:401–7.

16. Dienz O, Rud JG, Eaton SM, Lanthier PA, Burg E, Drew A, et al. Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. Mucosal Immunol 2012;5:258–66.

17. Liang X, Wang RS, Wang F, Liu S, Guo F, Sun L, et al. Sodium butyrate protects against severe burn-induced remote acute lung injury in rats.

PLoS One 2013;8:e68786.

18. Hodgman EI, Subramanian M, Arnoldo BD, Phelan HA, Wolf SE. Future Therapies in Burn Resuscitation. Crit Care Clin 2016;32:611–9.

19. van Haren F, Zacharowski K. What’s new in volume therapy in the intensive care unit? Best Pract Res Clin Anaesthesiol 2014;28:275–83.

20. Ma B, Zhou PY, Ni W, Wei W, Ben DF, Lu W, et al. Inhibition of activin receptor-like kinase 5 induces matrix metallopeptidase 9 expression and aggravates lipopolysaccharide-induced pulmonary injury in mice. Eur Rev Med Pharmacol Sci 2013;17:1051–9.

21. Miyashita T, Ahmed AK, Nakanuma S, Okamoto K, Sakai S, Kinoshita J, et al. A Three-phase Approach for the Early Identification of Acute Lung Injury Induced by Severe Sepsis. In Vivo 2016;30:341–9.

22. Moorthy AN, Tan KB, Wang S, Narasaraju T, Chow VT. Effect of High-Fat Diet on the Formation of Pulmonary Neutrophil Extracellular Traps during Influenza Pneumonia in BALB/c Mice. Front Immunol 2016;7:289.

23. Rizzo AN, Sammani S, Esquinca AE, Jacobson JR, Garcia JG, Letsiou E, et al. Imatinib attenuates inflammation and vascular leak in a clinically relevant two-hit model of acute lung injury. Am J Physiol Lung Cell Mol Physiol 2015;309:1294–304.

24. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2013;28:CD000567.

25. Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, et al.

Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol 2016;1:16031.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Tavşanlarda kombine travmanın neden olduğu akciğer yaralanmasında farklı tedavi protokollerinin değerlendirilmesi Dr. Xiao Bing Li Tianjin Birinci Merkezi Hastanesi, Yanık ve Plastik Cerrahi Bölümü, Tianjin-Çin Halk Cumhuriyeti

AMAÇ: Kombine travmanın neden olduğu akciğer yaralanmasında farklı tedavi rejimlerinin etkinliğini değerlendirmeyi amaçlamaktadır.

GEREÇ VE YÖNTEM: Tavşanlar ölümcül olmayan iki taraflı kapalı göğüs kontüzyonu ardından tüm vücut alanının %30’unu tutan haşlanma yanığına maruz bırakıldı. Tavşanlar minimum ortalama arter kan basıncı 70 mmHg’nin üç yöntemle başka bir deyişle 1:1, 1:2 veya 1:3 oranında normal salin/ poligelin enjeksiyonları ile idame ettirilen resüsitasyon gruplarından birine randomize edildi (sırasıyla, 1:1G, 1:2 G ve 1:3 G). Travmadan sonra akciğer yaralanması ıslak/kuru (I/K) akciğer ağırlığı oranı, ELISA ve gerçek zamanlı PCR analiziyle değerlendirildi.

BULGULAR: 1:1 veya 1:2 sıvı resüsitasyon grubuna göre 1:3 sıvı resüsitasyon grubunda tavşanlarda azalmış akciğer I/K oranı, alveoler kanama, MPO aktivitesi ve serumda düşük IL-8 ve TNF-α düzeyleri saptandı. Ayrıca 1:3 sıvı resüsitasyonu uygulanan tavşanlarda kombine yaralanmadan 24 saat sonra ultrastrüktürel değişiklikler de azaldı.

TARTIŞMA: Bu çalışma kombine yaralanmaya maruz kalan akciğerde sıvı resüsitasyonunun etkisini göstermiştir. Akciğer yaralanmasının erken evresinde kombine akciğer kontüzyonu ve yanık yaralanmasından sonra 1:3 sıvı resüsitasyonuyla tedavi daha efektiftir.

Anahtar sözcükler: Akciğer kontüzyonu; akut akciğer yaralanması; sıvı resüsitasyonu; yanık yaralanması.

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doi: 10.5505/tjtes.2017.21736

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EXPERIMENTAL STUDY

Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model Gökay Ateş, M.D.,1 Ferda Yaman, M.D.,1 Bülent Bakar, M.D.,2 Üçler Kısa, M.D.,3 Pınar Atasoy, M.D.,4 Ünase Büyükkoçak, M.D.1 1

Department of Anesthesiology and Reanimation, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

2

Department of Neurosurgery, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

3

Department of Biochemistry, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

4

Department of Pathology, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

ABSTRACT BACKGROUND: Blunt thoracic injury often leads to pulmonary contusion and the development of acute respiratory distress syndrome, which carries a high risk of morbidity and mortality, originating from the local and systemic inflammatory states. This study aimed to investigate the local and systemic antiinflammatory effects of levosimendan in rat models of blunt chest trauma.

METHODS: A total of 32 Wistar albino rats were randomly assigned to one of the following four groups: control, sham, low-dose levosimendan (LDL) (5 µg/kg loading dose for 10 min and 0.05 µg/kg/min intravenous infusion), and high-dose levosimendan (HDL) (10 µg/kg loading dose for 10 min and 0.1 µg/kg/min intravenous infusion). Blunt chest trauma was induced, and after 6 h, the contused pulmonary tissues were histopathologically and immunohistopathologically evaluated, serum TNF-α, IL-1β, IL-6, and NO levels were biochemically evaluated.

RESULTS: The mean arterial pressure was low throughout the experiment in the LDL and HDL groups, with no statistically difference between the groups. Levosimendan reduced the alveolar congestion and hemorrhage, which developed after inducing trauma.

Neutrophil infiltration to the damaged pulmonary tissue was also reduced in both the LDL and HDL groups. In rats in which pulmonary contusion (PC) was observed, increased activation of nuclear factor kappa B was observed in the pulmonary tissue, and levosimendan did not reduce this activation. Both high and low doses of levosimendan reduced serum IL-1β levels, and high doses of levosimendan reduced IL-6 and NO levels. TNF-α levels were not reduced.

CONCLUSION: In conclusion, the results showed that in a rat model of PC, the experimental agent levosimendan could reduce neutrophil cell infiltration to damaged pulmonary tissues and the systemic expressions of some cytokines (IL-1β, IL-6, and NO), thereby partially reducing and/or correcting pulmonary damage. Systemic inflammatory response that occurs after trauma could also be reduced.

Keywords: Blunt chest trauma, levosimendan; inflammation; lung contusion; nuclear factor-κB.

INTRODUCTION The pulmonary contusion (PC) table associated with blunt chest trauma is a clinical table observed with alveolar congesAddress for correspondence: Ferda Yaman, M.D. Dr. Ahmet Taner Kışlalı Caddesi, Deniz Sitesi, 9. Blok, No: 5, Kat: 3, Çayyolu, Ankara, Turkey Tel: +90 318 - 444 40 71 E-mail: ferdayaman@gmail.com Submitted: 14.03.2016 Accepted: 07.11.2016

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tion, hemorrhage, destruction of the alveolar structure integrity, edema, leukocyte infiltration, and hypoxemia with severe hypercarbia, and the course may vary with an increased respiratory burden.[1,2] In 2009, Hoth et al. reported that PC that develops because of blunt thoracic trauma stimulates the systemic natural immune response and causes an increase in proinflammatory cytokines.[3] The activation of the immune system, which occurs after massive injury, and the early inflammatory immune response, which is developed, is defined as systemic inflammatory response syndrome.[4] It has been shown in the literature that nuclear factor kappa B (NF-κB) has a significant role in controlling the expression of mediators, including inflammation-related factors, TNF-α, IL-1β, and adhesion molecules, which emerge in association with acute pulmonary injury and acute respiratory distress synUlus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Ateş et al. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

drome (ARDS).[5–7] Blunt chest trauma and PC, which develops with all of these features, have a high risk of morbidity and mortality.[8,9] Levosimendan increases the affinity of Ca2+ to troponin C (TnC) and is a pyridazinone-dinitrile-derived class III Ca2+sensitizing agent. By providing a dose-dependent connection of Ca2+ to the TnC N-terminal region, troponin activation is provided by inhibiting troponin I (TnI) and TnC-Ca2+ stabilization.[10] At the same time, levosimendan is a new drug that increases cardiac output with positive inotropic and vasodilation properties, without increasing the need for myocardial oxygen consumption. It has also been shown in the literature that besides these properties, oxidative pulmonary damage associated with reperfusion and inflammatory cytokines (IL1, IL-6, TNF-α, etc.) in ventilator-related pulmonary damage and sepsis experimental models are reduced, and cellular level inflammation and proinflammatory responses are suppressed.[11–14] This study outlines the therapeutic properties and effects of levosimendan on the potential systemic antiinflammatory response in an experimental rat model of unilateral PC.

MATERIALS AND METHODS Material This experimental study was performed according to the guidelines for the use of laboratory animal subjects in research set by the Ethics Committee of Kırıkkale University (Date: 02.13.2014; Number: 14/03-33).

In this experimental study, the experimental agent levosimendan (Simdax, Orion Corporation, Finland) was intravenously infused at a low dose (5 µg/kg loading dose for 10 min, followed by 0.05 µg/kg/min maintenance dose) and a high dose (10 µg/kg loading dose for 10 min and 0.1 µg/kg/min maintenance dose). The oral LD50 dose of levosimendan is defined as 980 mg/kg in rats.

A total of 32 male Wistar albino rats, each weighing 300–350 g, were used in the study. The number of rats to be included in the groups was determined based on similar studies in the literature, and the number of rats to be used was confirmed by power analysis. The rats were randomly allocated to one of the following four groups.

- Control group (n=8; sedation anesthesia was administered but no contusion was induced) - Sham group (n=8; after inducing contusion, 1.5 ml/100 g/h of physiological saline was intravenously administered) - Low-dose levosimendan (LDL) group (after inducing contusion, levosimendan was administered as a 5-µg/kg loading dose for 10 mins, followed by 0.05 µg/kg/min as an intravenous infusion) Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

- High-dose levosimendan (HDL) group (after inducing contusion, levosimendan was administered as a 10-µg/kg loading dose for 10 mins, followed by 0.1 µg/kg/min as an intravenous infusion) For sedation anesthesia, 40 mg/kg ketamine HCl (Ketalar® 5%; Pfizer Inc., USA) and 5 mg/kg xylazine HCl (Rompun® 2%; Bayer HealthCare AG, Germany) were intraperitoneally administered.

Method With all rats under sedation anesthesia, a vascular route was opened from the tail veins using a 24G yellow intracatheter.

Invasive monitorization was performed for 6 h for each rat fixed on a fixation plate, the left femoral artery was explored, and a catheter was placed in the artery under microscope guidance. After these preparatory procedures, unilateral pulmonary injury was induced in the right hemithorax of each rat via a modified form of the trauma mechanism developed

by Raghavendran et al. (with the method of a 0.5 kg cylindrical body falling from a height of 0.4 m; energy created, E=1.96 J) (Fig. 1).[15] To reduce cardiac injury to a minimum and have a minimum effect on hemodynamic instability, the contusion was unilaterally induced to the right lung.

Then, keeping the control group aside, the rats of the sham group were administered 1.5 ml/100 g/h of physiological saline infusion; those of the LDL group were administered levosimendan as a 5-µg/kg loading dose for 10 min, followed by 0.05 µg/kg/min intravenous infusion; and those of the HDL group were administered levosimendan as a 10-µg/kg loading dose for 10 min, followed by 0.1 µg/kg/min intravenous infusion. Throughout the experiment, systolic and diastolic blood pressures, mean arterial pressures, and heart rates (HRs) of all rats were monitored and recorded (Fig. 1). The rats were kept warm under a blanket throughout the experiment, and oxygen support was provided. After 6 h, median sternotomy was performed for all the rats under anesthesia, and euthanasia was performed by draining all the blood from the body via the cardiac route. The right lung was completely excised

(a)

(b)

Figure 1. Arterial pressure monitorization (a) and blunt thorax trauma experiment mechanism (b).

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Ateş et al. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

from each rat. The tissues and blood samples obtained were used for pathological, Immunohistochemical, and biochemical analysis.

Histopathological Evaluation After fixation of the pulmonary tissues obtained in 10% formaldehyde solution, the samples were embedded in paraffin blocks, and then, 5-µm-thick slices were cut and stained with hematoxylin and eosin. The preparates obtained were evaluated using a light microscope (Leica DM 2500) by an experienced pathologist who was blinded to the study groups. The areas of lung contusion were classified according to the presence of neutrophil infiltration, alveolar hemorrhage, alveolar congestion, and hyaline membrane formation, as described below (Fig. 2).

- Grade 0: minimal damage - Grade 1: little damage - Grade 2: moderate damage - Grade 3: severe damage

(a)

(b)

Immunohistochemical Evaluation Pulmonary tissues were washed with 4% paraformaldehyde, and after dehydration, they were embedded in paraffin blocks. Using standard histological techniques, 5-µm-thick slices were cut. All slices were heated at 60°C for 60 min in an oven and then deparaffinized. After the endogenous peroxidase reaction, blocking was performed using 3% H2O2 for 30 min. The samples were then washed thrice using a phosphate-buffered solution and incubated overnight in a solution of anti-rat NF-κB polyclonal antibody (Santa Cruz, CA, USA), which was diluted at room temperature 1/100 with primary rabbit. Biotin peroxide and diaminobenzidine brown-yellow colors were used in the development of the findings. The results obtained were evaluated by an experienced pathologist who was blinded to the study groups, and the NF-κB values in each slice were classified under a microscope (BenchMark GX, Ventana Medical Systems Inc.) using the histopathological classification method stated above.

Biochemical Evaluation The blood samples obtained from the rats were centrifuged at 3000 rpm for 10 mins; the serum samples were collected and immediately frozen in dry air at −80°C and stored until analysis. All serum samples were evaluated with respect to IL1β, IL-6, TNF-α, and NO levels by an experienced biochemist who was blinded to the study groups. The Platinum ELISA kit method was used for all serum samples (Affymetrix, eBioscience Inc., USA), and the results were calculated as pg/ml for IL-1β and IL-6, ng/L for TNF-α, and as μmol/L for NO.

Statistical Analysis All statistical analyses were conducted using the SPSS 22.0 statistical software (SPSS Inc., Chicago IL, USA).

(c)

(d)

Figure 2. Areas of neutrophil infiltration, alveolar hemorrhage, and alveolar congestion in the alveolar wall showing Grade 1 on the left and grade 3 on the right (HE; ×100) (a-c); stained areas in the lung showing grade 1 NF-κB and grade 3 on the right (×200) (d).

370

The histopathological grades and TNF-α levels that were not normally distributed and the variation was not homogenous between all groups were statistically analyzed using Kruskal–Wallis test. To determine the statistical differences between the groups (post hoc evaluation), Mann–Whitney U test (with Bonferroni correction) was performed for all grade results. p values of <0.0083 were considered to be significant.

The values of the hemodynamic parameters and IL-1β, IL6, and NO levels were normally distributed, and the variations were homogenous among the groups. Therefore, oneway analysis of variance (ANOVA) was performed for all the values. To determine the statistical differences between the groups, post hoc evaluation (one-way ANOVA–Tukey multiple comparisons test) was performed. p values of <0.05 were considered to be significant.

RESULTS Hemodynamic Measurement Evaluation Throughout the 6 h of the experiment, the systolic and diaUlus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Ateş et al. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

stolic blood pressures, mean arterial pressures, and HRs of all the rats were monitored and recorded. After inducing the trauma, bradycardia and hypotension developed in all the rats. At 20 min after the trauma, HR values were significantly higher in the LDL and HDL groups than in the sham group (p=0.031). The mean arterial pressure values tended to be high in the sham group after 30 min, and after 6 h, the val-

ues reached the baseline values. In the LDL and HDL groups, the mean arterial pressure values were observed to be low throughout the experiment, with no statistically significant difference observed between the groups.

Histopathological Evaluation Statistical analysis of the results of the histopathological ex-

Table 1. Descriptive table of the histopathological grades Group Variable

Minimum Maximum Mean/Median(*)

Standard deviation

Control

Alveolar congestion

0

1

0* 0.35

Alveolar hemorrhage

0

1

0* 0.35

Hyalen membrane

0

0

0* 0.00

Neutrophil infiltration

0

1

0* 0.35

NF-kB

0 1

0* 0.35

TNF-α

43.85 52.88

46.71* 4.12

IL-1β

285.70 548.20

408.03

IL-6

19.19 45.66

2941

9.97

NO

6.13 11.87

8.71

2.23

SHAM

Alveolar congestion

1

2

1* 0.52

Alveolar hemorrhage

1

3

1* 0.74

Hyalen membrane

0

0

0* 0.00

Neutrophil infiltration

1

2

1* 0.35

NF-kB

1 3

102.20

2* 0.84

TNF-α

45.67 119.83

76.07* 23.89

IL-1β

801.70 2161.60

1412.60

480.41

IL-6

22.64 59.47

36.74

12.93

7.34 14.19

10.08

2.24

NO

LDL

Alveolar congestion

1

3

1.5* 0.74

Alveolar hemorrhage

0

3

1* 0.92

Hyalen membrane

0

1

0* 0.35

Neutrophil infiltration

0

1

0* 0.52

NF-kB

1 3 1.5* 0.74

TNF-α

44.53 82.05

53.82* 12.80

IL-1β

443.80 1157.00

863.90

238.49

IL-6

16.89 33.00

23.36

6.30

NO

6.81 15.05

11.13

3.24

HDL

Alveolar congestion

0

2

1* 0.52

Alveolar hemorrhage

0

2

0* 0.76

Hyalen membrane

0

0

0* 0.00

Neutrophil infiltration

0

1

0* 0.46

NF-kB

1 2

1* 0.46

TNF-α

43.55 61.76

48.66* 6.03

IL-1β

407.70 991.40

670.59

220.86

IL-6

15.74 27.25

20.92

3.94

NO

4.58 8.70

6.80

1.60

Median values. LDL: Low dose levosimendan; HDL: High dose levosimendan; NF-κB: Nuclear factor kappa B; TNF-α: Tumor necrosis factor alpha; IL6: Interleukin 6; NO: Nitric oxide; IL-1B: Interleukin 1 beta.

*

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Ateş et al. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

Table 2. The statistically significant differences among all the groups described in the text with regard to alveolar congestion, alveolar hemorrhage, neutrophil infiltration, and NF-κB levels Variable

X2

df p

Alveolar congestion

17.965

3

<0.001

Alveolar hemorrhage

14.750

3

0.002

Hyalene membrane

3.000

3

0.392

Neutrophil infiltration

15.001

3

0.002

NF-kB

18.619 3 <0.001

TNF-α

11.994 3 0.007

Kruskal–Wallis multiple variant analysis; p<0.05 (df, degrees of freedom; X , chisquare).

2

NF-κB: Nuclear factor kappa B; TNF-α: Tumor necrosis factor alpha.

amination revealed a difference among the groups with respect to alveolar congestion (X2=17.965; p<0.001), alveolar hemorrhage (X2=14.750; p=0.002), neutrophil infiltration (X2=15.001; p=0.002), and NF-κB (X2=18.619; p<0.001).

No statistically significant difference was determined among the groups with regard to hyaline membrane formation (X2=3.000; p=0.392) (Tables 1, 2, and 3; Fig. 3).

A statistically significant difference was determined among the following groups with respect to alveolar congestion: control/sham (Z=−3.340; p=0.001); control/LDL (Z=−3.354; p=0.001), and control/YDL (Z=−2.887; p=0.004). No difference was observed among the groups with regard to the reduction of alveolar congestion. In addition, a statistically significant difference was determined among the groups with regard to alveolar hemorrhage: control/sham (Z=−3.332; p=0.001) and control/LDL (Z=−2.912; p=0.004). No difference was observed among the groups with respect to the reduction of alveolar hemorrhage.

A statistically significant difference was determined among the groups with respect to neutrophil infiltration: control/ sham (Z=−3.359; p=0.001), sham/YDL (Z=−2.646; p=0.008), and sham/LDL (Z=−2.988; p=0.003). Neutrophil infiltration was higher in the sham group than in the other groups. From this, it was determined that LDL and HDL reduced neutrophil infiltration in the pulmonary tissue with contusion (Table 3).

Immunohistochemical Evaluation NF-κB levels were different among all the groups: control/sham (Z=−3.385; p=0.001), control/LDL (Z=−1.118; p=0.001), and

Groups Sham

Groups LDL

YDL

Control

6

6

4

4

Count

Count

Control

2

0

Sham

LDL

LDL

2

0

1

2

0 1 2 0 1 2 Neutrophile infiltration

0

1

0

2

0 1 2 3

0 1 2 3 0 1 2 3 Alveolar haemorrhage

Groups Control

Sham

0 1 2 3

Groups LDL

YDL

Control

Sham

LDL

YDL

8 6

4

Count

Count

6

2

0

4

2

0 1 2 3

0 1 2 3 0 1 2 3 Alveolar congestion

0 1 2 3

0

0

1

0 0 1 1 Hyalene membrane

0

1

Figure 3. Variation of histopathological grades of each group. Each bar shows neutrophil infiltration, alveolar hemorrhage, alveolar congestion, and hyaline membrane values.

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Ateş et al. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

Table 3. Low and high doses of levosimendan reduced

neutrophil infiltration in the pulmonary

contusion tissue Variable

Groups

Z

Table 4. Descriptive table of the mean values of IL-1β, IL-6, and NO and median values of TNF-α levels Variable F df p p IL-1B 16.719 3 <0.001

Alveolar Control/Sham

-3.340 0.001

IL-6

4.955 3 0.007

NO

4.855 3 0.008

congestion

Control/LDL -3.354 0.001

Control/HDL -2.887 0.004

Sham/LDL

-0.657 0.511

Sham/HDL

-1.356 0.175

LDL/HDL

-1.767 0.077

Alveolar

Control/Sham -3.332 0.001

hemorrhage

Control/LDL -2.912 0.004

Control/HDL

-1.179 0.239

Sham/LDL

-0.061 0.952

Sham/HDL

-2.227 0.026

LDL/HDL

-1.947 0.052

Neutrophil

Control/Sham -3.359 0.001

infiltration

Control/LDL

-1.118 0.264

Control/HDL

-0.620 0.535

Sham/LDL -2.646 0.008 A statistically significant difference was determined with Sham/HDL -2.988 0.003 respect to serum NO levels only between the sham/YDL

LDL/HDL

NF-kB

Control/Sham -3.385 0.001

Control/LDL -3.354 0.001

Control/HDL -3.335 0.001

Sham/LDL

-0.623 0.533

Sham/HDL

-1.651 0.099

LDL/HDL

-1.108 0.268

TNF-α

Control/Sham -2.941 0.003

Control/LDL

-1.787 0.074

Control/HDL

-0.630 0.529

Sham/LDL

-1.892 0.059

Sham/HDL

-2.521 0.012

LDL/HDL

-1.156 0.248

-.522 0.602

Mann–Whitney U test and Bonferroni multiple comparison test; p<0.0083.

LDL: Low dose levosimendan; HDL: High dose levosimendan; NF-κB: Nuclear factor kappa B; TNF-α: Tumor necrosis factor alpha.

control/YDL (Z=−3.335; p=0.001) (Table 3). Although NF-kB levels were not statistically significantly different among the groups, the levels were numerically lower in the LDL and HDL groups than in the control and sham groups.

Biochemical Evaluation Statistical analysis of the results of the biochemical evaluation revealed a difference among the groups with respect to the serum levels of IL-1β (F=16.719; p<0.001), IL-6 (F=4.955; p=0.007), NO (F=4.855; p=0.008), and TNF-α (X2=11.994; p=0.007) (Table 4, 5, Fig. 4).

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

p<0.05. SD: Standard deviation. IL-1B: Interleukin 1 beta; IL6: Interleukin 6; NO: Nitric oxide.

A statistically significant difference was determined among the groups regarding serum IL-1β levels: control/sham (p<0.001), control/LDL (p=0.022), sham/LDL (p=0.005), sham/LDL (p<0.001), and LDL/YDL (p=0.005). Reduced serum IL-1β levels were observed in the LDL and HDL groups.

A statistically significant difference was determined among the groups with regard to serum IL-6 levels: sham/LDL (p=0.028) and sham/YDL (p=0.008). The use of HDL significantly reduced serum IL-6 levels.

(p=0.005) and LDL/YDL (p=0.006) groups (Table 5). HDL significantly reduced serum NO levels.

Serum TNF-α levels were different only between the control/ sham (Z=−2.941; p=0.003) groups (Table 3).

DISCUSSION Previous studies demonstrated that the effect of chest trauma increased with the occurrence of respiratory complications, such as ALI/ARDS, associated with the trauma severity.[16–18] In patients with multiple trauma, if PC occurs, the mortality rate increases from 27% to 56%. In addition, animal experimental studies revealed that after trauma, there are severe local and systemic inflammatory changes, which potentially trigger septic complications, and the organ failure that first develops in this table is respiratory failure.[19] In the current study, an increase in the systemic inflammatory response and development of severe bradycardia and hypotension, as a clinical reflection, were observed more in the trauma groups than in the control group. In the LDL and HDL groups, where doses administered were similar to those in used in the clinical practice, the mean arterial pressure significantly reduced. In the clinical practice, levosimendan is administered for hypotension, and so, to observe the effect on hypotension in the current study, the following two different doses were administered: 5 µg/kg loading dose for 10 min, followed by 0.05 µg/kg/min intravenous infusion, and 10 µg/kg loading dose for 10 min, followed by 0.1 µg/kg/min intravenous infusion. No statistically significant differences were observed with regard to the mean arterial blood pressure or heart rate in the LDL and HDL groups.

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Ateş et al. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

Table 5. The variations in mean values of IL-1β, IL-6, and NO were statistically significant among all groups Variable

Groups

Mean difference (I-J)

Standard Error

p

IL-1β Control/Sham

-1004.58

147.25 <0.001

Control/LDL

-455.88

147.25 0.022

-262.56

147.25 0.302

Sham/LDL

548.70

147.25 0.005

Sham/HDL

742.01

147.25 <0.001

Control/HDL

193.31

147.25 0.563

IL-6 Control/Sham

-7.34

4.48 0.376

Control/LDL

6.04

4.48 0.542

Control/HDL

8.49

4.48 0.254

Sham/LDL

13.38

4.48 0.028

Sham/HDL

15.82

4.48 0.008

LDL/HDL

2.45

4.48 0.947

NO Control/Sham

LDL/HDL

-1.37

1.20 0.669

Control/LDL

-2.41

1.20 0.207

Control/HDL

1.91

1.20 0.399

Sham/LDL

-1.05

1.20 0.818

Sham/HDL

3.28

1.20 0.050

LDL/HDL

4.33

1.20 0.006

One-Way ANOVA test, p<0.05. df: Degrees of freedom; F: F test. LDL: Low dose levosimendan; HDL: High dose levosimendan; IL6: Interleukin 6; NO: Nitric oxide; IL-1B: Interleukin 1 beta.

PC, which is widely observed after blunt thorax trauma, is an injury that may result in morbidity and mortality.[20] In the current study, because the results of the histopathological examination of pulmonary tissues obtained 6 h after the formation of blunt thorax trauma, which included alveolar hemorrhage, alveolar edema, and neutrophil infiltration, were similar to the those of the trauma model described by Raghavendran et al., the efficacy of the current study model was confirmed.

[15] According to these results, PC model was successfully established in the rats. After analyzing the results obtained from the histopathological examination in this study, although a statistical difference was not observed, when the median values were examined, the high dose of levosimendan was considered to reduce alveolar hemorrhage that developed after trauma; however, when a low dose was administered, no effect on alveolar hemorrhage was observed. In addition, at both low and high doses, levosimendan reduced neutrophil infiltration in damaged pulmonary tissues. However, levosimendan did not have any effect on reducing alveolar congestion. Based on these findings, it was considered that levosimendan did not reduce alveolar congestion but was effective in reducing inflammatory cell infiltration and alveolar hemorrhage in PCs that developed after blunt thoracic trauma.

In experimental studies of pulmonary damage, an intense inflammatory response developed in damaged tissues, and the 374

chemokines that were particularly expressed by alveolar macrophages activated neutrophils.[21] It has been proposed that reactive oxygen radicals, tissue fragmenting proteinases, and cationic polypeptides in proinflammatory cytokines (e.g., IL1β, IL-6, TNF-α, and NO), expressed by active neutrophils, are a risk factor for increase in tissue damage and the development of ARDS.[22] NF-κB, a proinflammatory factor, has a regulatory role in the emergence of several of the abovementioned mediators.[7] In an experimental animal model study

by Perl et al.,[23] the inflammatory effects of PC were examined in mononuclear cells in the peripheral blood, peritoneal macrophages, splenocytes, and splenic macrophages and on plasma TNF-α and IL-6 levels. At the end of the study, it was reported that PC caused severe immune function impairment systemically and in different compartments.

In the current study, PC induced in the rats increased NFκB activation in the pulmonary tissue, and levosimendan did not reduce this activation. Although statistical analysis did not reveal any difference between the groups, the TNF-α formation could have been suppressed in the serum samples of the LDL and HDL groups. While the serum IL-1β level reduced after administration of low and high doses of levosimendan, serum IL-6 and NO levels reduced with high doses only. In the current study, serum levels of the proinflammatory cytokines IL-1β and TNF-α significantly increased in Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

2500.00

60.00

2000.00

50.00

IL6 (pg/mL)

IL-1b (pg/mL)

Ateş et al. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model

1500.00

1000.00

500.00

40.00

30.00

20.00

.00

10.00 Control

Sham

LDL

YDL

Control

Sham

Group

LDL

YDL

LDL

YDL

Group

120.00 15.00

12.50

NO (umol/L)

TNF-a (ng/L)

100.00

80.00

10.00

7.50

60.00

5.00 40.00 Control

Sham

Group

LDL

YDL

Control

Sham Group

Figure 4. Mean values of IL-1β, IL-6, and NO and median value of TNF-α of all groups compared with the control group. Each error bar shows the minimum and maximum biochemical values.

the sham group compared with those in the control group.

These results suggested that proinflammatory cytokine formation after blunt thoracic trauma was suppressed by levosimendan.

Limitations This study had some limitations. First, this study evaluated the effects of levosimendan on the systemic inflammatory response, but for technical and financial reasons, advanced biochemical and histopathological examination of inflammatory response inhibitors, which are developed in damaged pulmonary tissues, were not performed. Second, the low and high doses of levosimendan used in this study were within the dose ranges recommended in the guidelines for the diagnosis and treatment of acute heart failure; therefore, it would be appropriate to conduct further studies of higher doses and assess the long-term effects of such doses.

If a more significant increase is observed in the antiinflammatory properties of HDL compared LDL, the selection of the dose to be used should be patient-based in the clinical use. Therefore, considering the effects of the local and systemic response on mortality following PC development after thorax trauma, further studies over a longer term with higher doses would be useful with respect to clinical safety.

Third, owing to technical and financial restrictions, arterial blood gas analysis was not performed, and saturation was not monitored.

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Conclusion In conclusion, the study results revealed that in a rat model of PC, the experimental agent levosimendan could reduce neutrophil infiltration to damaged pulmonary tissues and decrease the systemic release of some cytokines (such as IL1β, IL-6, and NO), thus partially reducing and/or correcting pulmonary damage. Therefore, levosimendan is considered to reduce systemic inflammatory responses that occur after trauma and is clinically beneficial for patients with PC.

Funding This study was supported by Kırıkkale University Scientific Research Council (2014/84).

Conflict of interest: None declared.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel künt toraks travma modelinde levosimendanın sistemik antienflamatuvar etkilerinin araştırılması Dr. Gökay Ateş,1 Dr. Ferda Yaman,1 Dr. Bülent Bakar,2 Dr. Üçler Kısa,3 Dr. Pınar Atasoy,4 Dr. Ünase Büyükkoçak1 Kırıkkale Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Kırıkkale Kırıkkale Üniversitesi Tıp Fakültesi, Beyin ve Sinir Cerrahi Anabilim Dalı, Kırıkkale Kırıkkale Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, Kırıkkale 4 Kırıkkale Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Kırıkkale 1 2 3

AMAÇ: Künt toraks travması sıkılıkla pulmoner kontüzyona yol açar, lokal ve sistemik enflamatuvar durumlardan kaynaklanan yüksek morbidite ve mortalite riski taşıyan akut solunum sıkıntısı sendromunun gelişmesine neden olur. Bu çalışmanın amacı sıçanlarda künt göğüs travma modelinde levosimendanın lokal ve sistemik antienflamatuvar etkilerini araştırmaktır.

GEREÇ VE YÖNTEM: Otuz iki Wistar Albino sıçan dört gruba ayrıldı: Kontrol, Sham, düşük doz levosimendan (LDL) (5 µg/kg 10 dakika yükleme doz, 0.05 µg/kg/dk intravenöz infüzyon) ve yüksek doz levosimendan (YDL) (10 µg/kg 10 dakika yükleme doz, 0.1 µg/kg/dk intravenöz infüzyon) grubu olarak belirlendi. Künt göğüs travmasından altı saat sonra histopatolojik ve immünohistokimyasal değerlendirme için kontüze pulmoner dokular çıkarılmıştır ve serumda TNF-α, IL-1β, IL-6, NO düzeyleri biyokimyasal olarak değerlendirildi.

BULGULAR: Düşük doz levosimendan ve YDL grubunda ortalama arter basınçları deney boyunca düşük seyretti ve aralarında istatistiksel olarak anlamlı fark saptanmadı. Levosimendanın travma sonrası oluşan alveolar konjesyonu ve hemorajiyi azaltmadığı saptandı. Ancak levosimendanın düşük ve yüksek dozlarda hasarlı akciğer dokusuna nötrofil infiltrasyonunu azalttığı tespit edildi. PC oluşturulan sıçanlarda akciğer dokusunda NFκB’nin aktivasyonunun arttığı ancak levosimendanın bu aktivasyonu azaltamadığı gözlendi. Öte yandan levosimendanın düşük ve yüksek dozlarda verildiğinde serum IL-1β seviyesini azalttığı; yüksek dozlarda uygulandığında da IL-6 ve NO oranlarını azalttığı tespit edildi. Ancak serum TNF-α seviyelerini azaltamadığı saptandı.

TARTIŞMA: Sonuç olarak levosimendan isimli deneysel ajanın sıçanlarda oluşturulan pulmoner kontüzyon modelinde hasarlı akciğer dokusuna nötrofil hücre infiltrasyonunu ve bunlardan salınacak bazı sitokinlerin (IL-1β, IL-6, NO) sistemik salınımını azaltabileceği ve böylece pulmoner hasarı kısmen azaltabileceği ve/ veya düzeltebileceği; travma sonrası ortaya çıkan sistemik enflamatuvar yanıtı da azaltabileceği düşünülmüştür.

Anahtar sözcükler: Akciğer kontüzyonu; B, enflamasyon, künt göğüs travması, levosimendan; nükleer faktör κ.

Ulus Travma Acil Cerrahi Derg 2017;23(5):368–376

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doi: 10.5505/tjtes.2016.26786

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EXPERIMENTAL STUDY

Separate and synergistic effects of taurolidine and icodextrin in intra-abdominal adhesion prevention Necmi Kurt, M.D., Hasan Ediz Sıkar, M.D., Levent Kaptanoğlu, M.D., Hasan Fehmi Küçük, M.D. Department of General Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, Istanbul-Turkey

ABSTRACT BACKGROUND: In our present study, we aimed to evaluate the effects of taurolidine, a blocking agent of fibrin deposition, and icodextrin, a colloid osmotic material that also inhibits fibrin accumulation, and the effect of their application separately and concomittantly in intra-abdominal adhesion prevention.

METHODS: Forty BALB/c male mice, weighing 30–35 g and 11–12 weeks old were divided into four groups as follows: group 1: control group, group 2: taurolidine group, group 3: icodextrin group, and group 4: taurolidine and icodextrin group. Animals were sacrificed by cervical dislocation after 14 days. The adhesions were classified and scored by two blinded researchers according to Nair’s macroscopic adhesion staging system and microscopically evaluated using Zuhlke classification system.

RESULTS: In group 2 there was no mice with score 4. In group 3, scores 3 and 4 were absent. Scores 2, 3, and 4 were not detected in group 4. The mean value of adhesion scores decreased from groups 1 to 4. There was a significant statistical difference between all the groups and group 1. There was no change between the study groups on macroscopic examination, whereas histopathological examination revealed statistically significance between group 4 and other groups.

CONCLUSION: Taurolidine and icodextrin, when used alone or together, decrease postoperative intra-abdominal adhesion formation. Macroscopic appearence was not supportive of statistical difference between group 4 and other groups. Microscopic evaluation paves the road for future studies for determining significance when taurolidine and icodextrin are applied concomittantly. Additional experimental studies are required for dose adjustment.

Keywords: Icodextrin; surgical adhesions; taurolidine.

INTRODUCTION Adhesions form as a natural part of the body’s healing process after surgery in a similar manner as scars. The term adhesion is commonly used when the scar extends from within one tissue across another tissue, usually across the peritoneal cavity in surgical cases. Postsurgical adhesions commonly occur when two separate surfaces are close to one another. This type of formation may cause inflammation and accumulation of fibrin deposits on damaged tissues. Fibrin then connects two separate tissues and acts like a glue to seal the injured Address for correspondence: Hasan Ediz Sıkar, M.D. Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 216 - 458 30 00 E-mail: hasan.sikar@me.com Submitted: 01.10.2016 Accepted: 23.12.2016

Ulus Travma Acil Cerrahi Derg 2017;23(5):377–382 doi: 10.5505/tjtes.2016.01957 Copyright 2017 TJTES

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site. The rate of intra-abdominal adhesion formation following abdominal surgeries is 67%–93%.[1] Postoperative intraabdominal adhesions still remain as major obstacle in successful treatment of patients with acute mechanical intestinal obstruction.[2,3] Nearly 75% of these cases suffer from signs and symptoms of ileus. Our records describe a rate of 45.5%.

[4] Other consequences of intra-abdominal adhesions are as infertility, chronic pelvic pain, and major additive complications of secondary surgeries.[5] Postoperative intra-abdominal adhesions may cause a significant increase in hospital costs because of high morbidity and mortality rates.[3] Depending on the severity of the obstruction, a partial obstruction may relieve itself with a conservative approach. However, many adhesions require surgery for treatment. Therefore, various efforts have been made to overcome adverse effects of adhesions. Meticulous dissection of tissues to avoid surgical trauma, manipulation of time-consuming effect of ischemia time, absence of overheated liquids while washing the intestines, providing ideal surgical manipulation by appropriate use of devices such as ecarteurs or cautery have all limited impacts in adhesion prevention. Various agents, including pharmacological drugs and physical barriers, were administered to avoid 377

Kurt et al. Separate and synergistic effects of taurolidine and icodextrin in intra-abdominal adhesion prevention

adhesions. Taurolidine is an antimicrobial agent used to prevent intra-abdominal adhesion formation and sepsis in experimental and clinical trials. In previous studies, the blocking effects of taurolidine on fibrin deposition have been described.

[6] Icodextrin is an colloid osmotic material used in forming an aqueous solution for peritoneal dialysis and after gynecological procedures for reducing postoperative adhesions. The osmotic activity of icodextrin helps in separating tissues and reducing adhesive effects of fibrin. Tissues are kept from gluing together. In our present study, we aimed to evaluate effects of taurolidine and icodextrin in preventing intra-abdominal adhesions separately and to determine whether they have a synergistic effect when used concomitantly.

MATERIALS AND METHODS This present study was conducted at Pendik Veterinary Control and Research Institute Experimental Animals Unit. Our study was approved by the Pendik Veterinary Control and Research Institute Animal Experiments Local Ethics Committee (25/17). Forty BALB/c male mice, weighing 30–35 g and 11–12 weeks old, were bred in Pendik Veterinary Control and Research Institute. The animals were randomized into four groups, consisting of 10 rats as follows: group 1: control group, group 2: taurolidine group, group 3: icodextrin group, and group 4: taurolidine and icodextrin group. Animals were kept in eight cages (five mice in each) with satisfactory environment conditions and room temperatur e in 12 h day/night cycles with free access to water and specific pathogen-free conditions. All animals were fed a normal diet.

Surgical Technique All surgical procedures and approaches have been performed in semi-sterile environment. All animals were anesthetized with 4 mg/kg xylazine (Rompun, Bayer Turk Kimya San. Ltd. Sti., Istanbul, Turkey) and 100 mg/kg ketamine hydrocloride (Ketasol, Richter Pharma Ag, Wels, Austria) via the intramuscular route. Spontaneous breathing of mice has been provided perioperatively and with the help of a table lamp, the body temperature was maintained at 37°C. Prior to the incision, the abdominal space of all animals were cleaned and wiped with povidone iodide. Laparotomy was performed with a 15-mm midline incision. Two animals died because of adverse effects of anesthesia, but they were replaced with animals of the same species and gender. Initially, to achieve intraperitoneal adhesion, a cecal abrasion model was formed in all groups. Thus, following a 15-mm midline incision, the cecum was found and a 1 cm2 defect in the serous layer and an additional 1 cm2 peritoneal damage was created on the abdominal wall using a lancet. The intestines of all animals were re-placed into the abdominal cavity. In group 1 (n=10), the abdomen was closed without any pharmacologic agent administration (the control group). In group 2 (n=10), 1 ml (0.02 g) taurolidine (Taurolin®, Geistlich Sohns Ltd,Wolhusen, Switzerland) instillation was performed before closure (the 378

taurolidine group). In group 3 (n=10), 1 ml (0.04 g) icodextrin 4% (Adept®, Baxter Healthcare Corporation, Deerfield, USA) instillation was performed (the icodextrin group). Finally, in group 4 (n=10), the abdomen was closed following 0.5 ml (0.01 g) taurolidine and 0.5 ml (0.02 g) icodextrin 4% instillation (the taurolidine and icodextrin group).

All animals were kept for 14 days and sacrificed by cervical dislocation. The abdominal cavity was reopened with a reverse U-shaped incision. Adhesions were scored by two blind observers according to Nair’s macroscopic adhesion staging system, which has been used and tested before.[7] Cecum and adherent organs were extracted for histopathological analysis. All specimens were fixed in 10% formalin solution for histopathological evaluation. According to routine tissue processing, serial sections (5 µm) were stained with hematoxylin and eosin. Histopathological evaluation of the adhesions was performed by a blind investigator, following the rules followed

by Zühlke et al.[8] Statistical analysis was performed using the Statistical Package for Social Sciences software (SPSS Inc, vers. 13.0, Chicago, IL, USA). Numeric values were represented as n (number Table 1. The adhesion scoring system defined by Nair et al.

Score Explanation 0

Complete absence of adhesions

1

Single band of adhesions; between the viscera or from

one viscus to the abdominal wall

2

Two bands between viscera or from the viscera to

the abdominal wall

3

More than two bands; between viscera, from viscera

to the abdominal wall, or complete intestines forming

a mass without adhering to the abdominal wall

4

Viscera directly adherent to the abdominal wall

irrespective of the number and extent of adhesive bands

Table 2. Histological classification according to Zuhlke et al.

Score Explanation 1

Loose connective tissue, cell-rich, old and new fibrin,

fine reticulin fibers

2

Connective tissue with cells and capillaries and few

collagen fibers

3

More firm connective tissue, fewer cells, more

vessels, and few elastic and smooth muscle fibers

4

Old firm granulation tissue, cell-poor, serosal layers

that are hardly distinguishable

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Kurt et al. Separate and synergistic effects of taurolidine and icodextrin in intra-abdominal adhesion prevention

(a)

(b)

(c)

(d)

Figure 1. (a-d) Macroscopic findings. Single band of adhesions, score 1 (a). Two bands between viscera, score 2 (b). Complete intestines forming a mass, score 3 (c). Viscera directly adherent to the abdominal wall, score 4 (d).

RESULTS

are shown in Table 3; there was a statistically significant difference between all groups on overall comparison (p=0.007).

No mice was detected with score 4 in group 2; scores 3 and 4 in group 3; scores 2, 3, and 4 in group 4. There was a significant statistical difference between all the groups and the control group, whereas there was no statistical difference among the study groups (i.e., groups 2–4) (Table 4).

The adhesion scoring system defined by Nair et al was used in our study. Zero represents complete absence of adhesion, whereas 4 stands for viscera directly adherent to the abdominal wall. Table 1 describes the macroscopic scoring system. We tried to document our macroscopic findings in Figure 1. Adhesive band formation scores for specific groups

According to Zühlke et al’s histological classification system, 1 stands for loose connective tissue, whereas 4 represents old, firm granulation tissue. Table 2 describes histolopathological classification. There was no mice with score 4 in all groups. There was a significant statistical difference between

of mice), mean ± standard deviation. Overall comparison of the groups was performed using Kruskal–Wallis Test. Paired comparisons of the groups were performed by Mann–Whitney U Test. Based on the results of analyses, p value <0.05 was considered to be statistically significant.

Table 3. Adhesion scores of groups (macroscopic/microscopic) Adhesion Score

Group 1 (n=10)

0

Group 2 (n=10)

Group 3 (n=10)

Group 4 (n=10)

1 4 5 5

1

2/1 4/3 4/4 5/9

2

2/3 1/6 1/5 0/1

3

3/6 1/1 0/1 0/0

4

2/0 0/0 0/0 0/0

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Kurt et al. Separate and synergistic effects of taurolidine and icodextrin in intra-abdominal adhesion prevention

Table 4. Statistical comparison of adhesion degrees between groups

Macroscopic Evaluation

Histological Evaluation

Group 1 – Group 2

p=0.022

p=0.031

Group 1 – Group 3

p=0.006

p=0.022

Group 1 – Group 4

p=0.003

p<0.001

Group 2 – Group 3

p=0.53

p=0.7

Group 2 – Group 4

p=0.4

p=0.007

Group 3 – Group 4

p=0.83

p=0.021

all groups on overall comparison (p=0.001). Group 4 showed statistically significant difference compared with other groups (Table 4). Histological evaluation results are depicted in Figure 2. There were no deaths during the postoperative period.

DISCUSSION Postoperative intra-abdominal adhesion formation is a significant cause of morbidity and mortality and can also result in major technical difficulties during subsequent surgeries.

During surgical procedures within the abdominal cavity, injury and ischemia of the peritoneum may result in adhesion formation. In response to trauma and ischemia, the damage on the peritoneum is usually covered with neutrophils in 4 h.

Complete recovery takes place in nearly 1 week.[9–11] Though structurally different, the peritoneal recovery process is a biochemically inflammatory process and it is theoretically possible to manipulate this process using pharmacological agents, via their anti-inflammatory efficacy of resulting in increased fibrinolytic activity. In previous studies, non-steroidal anti-inflammatory drugs have been used, both perioperatively and postoperatively, for their anti-inflammatory effects on adhesion prevention. However, their impacts were insufficient and side effects remain as major obstacles in successful application.[12,13] Also, corticosteroids have been administered for preventing adhesions considering their suppressive effects against inflammatory response but have been found to be insufficient with low doses and serious side effects have been found with high doses.[14,15] Several pharmacological agents, such as high doses of vitamin E and simvastatin, were dis-

(a)

covered to have a high efficacy in adhesion prevention.[16–18] Taurolidine is an antimicrobial agent used for intra-abdominal adhesion formation and sepsis prevention in experimental and clinical trials. In previous studies, the blocking effects of taurolidine on fibrin deposition have been described.[6] Taurolidine prevents long-term postoperative inflammation.[19–21] Tarhan et al. reported that intraperitoneal administration of taurolidine increases t-PA levels and t-PA plasminogen activator inhibitor type-1 ratio. This mechanism explains the effect of taurolidine on the peritoneal fibrinolytic system.[22] Taurolidine also have antiendotoxic, antibacterial, and tumoricidal effects besides its adhesion preventive effect. Its antimicrobial capacity against gram-positive, gram-negative, and anaerobic bacteria and some fungi makes taurolidine an effective drug. It can be used in infections with resistance against a wide range of antibiotics, such as staphylococcus resistant to metisiline and enterococcus resistant to vancomycine.[19,23] In our study, taurolidine has been explored and evaluated for its adhesion preventive effects. A statistically significant adhesion preventive effect has been found compared with the control group.

We believe that taurolidine can be utilized for abdominal adhesion prevention.

Apart from pharmacological agents, physical barriers are also successful as they keep damaged surfaces apart during inflammatory response. As concomitant repair of the peritoneum takes place through all damaged surfaces, the ideal physical barrier should keep all peritoneal surfaces apart at the same time and for the same time period. Hyaluronic acid-saline buffered with phosphate combination or hyaluronic acid-

(b)

(c)

Figure 2. (a-d) Histological findings. Nearly normal serosal surface, score 1 (a). Serous membrane thickening, edema, score 2 (b). Fibrinous structure with serous membrane thickening, score 3 (c).

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carboxymethyl cellulose membrane has prevented peritoneal adhesions in a multicenter clinical trial.[24,25] Icodextrin is a colloid osmotic material used for forming an aqueous solution for peritoneal dialysis and after gynecological procedures for reducing postoperative adhesions. The osmotic activity of icodextrin helps in separating tissues and reducing adhesive effects of fibrin. Tissues are kept from gluing together. Icodextrin is a solution whose adhesion preventive effects have been proven in preclinical and clinical studies.[26–28] Its ability to keep both damaged and non-damaged peritoneal surfaces apart makes it an ideal physical barrier.

Icodextrin (4%) solution is not absorbed from the peritoneal space for 48 h; only half of it is absorbed in 96 h; thus, it continues showing its efficacy through the peritoneal surface for 3–5 days, which is a critical period for adhesion formation.[29] Besides, icodextrin has no effect on wound healing.[27] In our study, we have used icodextrin 4% in group 3 animals.

No adhesions of scores 3 and 4 have been detected. Compared with the control group, its adhesion preventive effect in group 3 has been found to be significant. We believe that anti-inflammatory effects and separation of damaged surfaces are required in combination for abdominal adhesion prevention. This synergistic impact can be achieved through the combined administration of taurolidine and icodextrin. Considering the features of these two different materials, we can predict that an ideal adhesion preventative material can be formed. Increased fibrinolytic activity and distance between peritoneal surfaces for a required period are the main goals of our study. Taurolidine and icodextrin, though having different mechanisms of activity, share similar usage patterns.

In particular, their efficacy does not alter with respect to the implementer as they have easy application features. Although these two agents have not been recently discovered, concomitant application has not been observed in literature. In our study, we detected high abdominal adhesion preventive effects of taurolidine and icodextrin. The difference has been found to be statistically significant.

In our study, compared with groups 2 and 3, no experimental animal in group 4 had a score of 2, 3, and 4 for adhesion severity In addition, some animals in group 4 showed nearly normal serosal surfaces on evaluation of histopathological specimens. We believe that the combined application of taurolidine and icodextrin could be responsible for this synergistic effect. Our evaluation using Zuhlke’s classification of histopathological tissues supported this idea.

Optimal dose of taurolidine and icodextrin in BALB/c species mice is not known; therefore, dose-dependent studies should be planned for future evaluations. Pharmacological agents, such as corticosteroids and vitamin E, has adhesion preventive effects at high doses.[14–17] Future studies may show similar impacts of taurolidine and icodextrin. In literature, there is a study in which in 2 ml (0.04 g) of taurolidine 2% solution Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

has been used as an adhesion preventative.[30] Results of that study were similar to our findings. They were not able to discover any dose-dependent effects.

Our current study is the first experimental design for determining the efficacy of icodextrin 4% solution in adhesion prevention. Our results revealed successful adhesion prevention using with 1 ml (0.04 g) icodextrin. Concomitant application of taurolidine and icodextrin 4% solution was also tested for the first time (0.5 ml). In light of this pioneer study, further evaluations for dose adjustment are required to overcome adverse effects of abdominal adhesions.

In conclusion, taurolidine and icodextrin, when used alone or together, decrease postoperative intra-abdominal adhesion formation. Macroscopic appearance was not supportive of statistical difference between taurolidine and icodextrin group and other groups. Microscopic evaluation paves the way for future studies as significant abdominal adhesion preventive effects were observed when taurolidine and icodextrin were applied concomitantly. Additional experimental studies are required for dose adjustment.

Conflict of interest: None declared.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Taurolidin ve icodextrin’in karıniçi yapışıklıkların önlenmesinde ayrı ve sinerjik etkileri Dr. Necmi Kurt, Dr. Hasan Ediz Sıkar, Dr. Levent Kaptanoğlu, Dr. Hasan Fehmi Küçük Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul

AMAÇ: Çalışmamızda fibrin oluşumunu engelleyen ajan olan taurolidin ve fibrin kümelenmesini engelleyen icodextrin’in ayrı ayrı ve birlikte uygulanmasının karıniçi yapışıklığın önlenmesine olan etkisini değerlendirmeyi amaçladık.

GEREÇ VE YÖNTEM: Kırk adet 30–35 gram ağırlığında, 11–12 haftalık erkek BALB/c fare, 4 gruba ayırıldı. Grup 1: Kontrol grubu, Grup 2: Taurolidin grubu, Grup 3: İsodekstrin grubu ve Grup 4: Taurolidin ve isodekstrin grubu olarak adlandırıldı. Deney hayvanları 14. gün servikal dislokasyonla sakrifiye edildiler. Yapışıklıklar iki kör araştırmacı tarafından Nair’in makroskobik yapışıklık skorlama sistemiyle sınıflandırıldı. Mikroskobik değerlendirme için Zühlke’nin sınıflandırması kullanıldı.

BULGULAR: Grup 2’de skor 4 olan fare olmadı. Grup 3’te skor 3 ve 4 olan fare yoktu. Skor 2, 3 ve 4 Grup 4’teki farelerde saptanmadı. Grup 1’den 4’e doğru yapışıklık skor ortalamalarının azaldığı görüldü. Kontrol grubuyla tüm çalışma grupları arasında istatistiksel açıdan anlamlı farklılık saptandı.

Makroskobik değerlendirmede çalışma grupları arasında farklılık saptanmazken histopatolojik incelemede Grup 4 ve diğer çalışma grupları arasında istatistiksel açıdan anlamlı farklılık saptandı.

TARTIŞMA: Taurolidin ve isodekstrin ayrı ayrı veya beraber kullanıldığında karıniçi yapışıklık oluşumunu azaltmaktadır. Makroskobik görünüm taurolidin ve isodekstrin grubuyla diğerlerinin istatistiksel açıdan farklılığını desteklememektedir ancak mikroskobik değerlendirme beraber kullanıldıklarında farklılık yaratması nedeniyle gelecek çalışmalara yol göstermektedir. Doz ayarlaması için ilave deneysel çalışmalar gereklidir.

Anahtar sözcükler: Icodextrin; peritoneal yapışıklık; taurolidin.

Ulus Travma Acil Cerrahi Derg 2017;23(5):377–382

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doi: 10.5505/tjtes.2016.01957

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

ORIG I N A L A R T IC L E

Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

Necdet Fatih Yaşar, M.D.,1 Mustafa Ufuk Uylaş, M.D.,1 Bartu Badak, M.D.,1 Uğur Bilge, M.D.,2 Setenay Öner, M.D.,3 Enver İhtiyar, M.D.,1 Tarık Çağa, M.D.,1 Ercüment Paşaoğlu, M.D.1 1

Department of General Surgery, Eskişehir Osmangazi University, Eskişehir-Turkey

2

Department of Family Medicine, Eskişehir Osmangazi University, Eskişehir-Turkey

3

Department of Biostatistics, Eskişehir Osmangazi University, Eskişehir-Turkey

ABSTRACT BACKGROUND: This study compared the predictive accuracy of four scoring systems, namely Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), and Mortality in Emergency Department (MEDS), for estimating prognosis in patients with necrotizing fasciitis.

METHODS: Seventy-four patients who presented with necrotizing fasciitis were retrospectively examined. The ability of the scoring systems to predict mortality was assessed by comparing the estimated mortality rates in mortality groups (survivors/non-survivors), and mortality rates among survivors and non-survivors with an estimated mortality of >10%, 30%, and 50% in the scoring systems were compared in pairs.

RESULTS: Estimated mortality rates in the survivor and non-survivor groups were different for all the scoring systems. The estimated mortality rates of APACHE II and SAPS II were much closer to the actual mortality rates than the other two scoring systems.

When the predicted mortality rates were analyzed as limits for a mortality risk, the predicted mortality rate by APACHE II was superior to that by SAPS II. CONCLUSION: The studied scoring systems had significantly higher predicted mortality rates in non-survivors than in survivors; however, they all underestimated the mortality rate. APACHE II and SAPS II were relatively superior for estimating mortality in patients with necrotizing fasciitis. APACHE II rather than the other scoring systems should be currently used.

Keywords: APACHE II; MEDS; necrotizing fasciitis; SAPS II; SOFA.

INTRODUCTION Necrotizing soft tissue infection defines a group of necrotizing infections of the skin, soft tissues, and muscles and is described as necrotizing fasciitis when it rapidly progresses through fascial planes. It may develop in the upper and lower extremities, perineum and genital area, and abdominal wall.

The clinical course may be swift owing to polymicrobial infection and synergy that cause the destruction of the fascia Address for correspondence: Necdet Fatih Yaşar, M.D. Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Meşelik Kampüsü, 26480 Eskişehir, Turkey Tel: +90 222 - 239 29 79 / 2600 E-mail: nfyasar@gmail.com Submitted: 30.03.2016 Accepted: 30.12.2016

Ulus Travma Acil Cerrahi Derg 2017;23(5):383–388 doi: 10.5505/tjtes.2016.19940 Copyright 2017 TJTES

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

at a rate of approximately 2–3 cm/h.[1,2] Therefore, the early diagnosis of necrotizing fasciitis is life-saving, whereas any delay may result in more extensive surgery, higher amputation rates, and higher mortality rates. Mortality rates are approximately 25% and if untreated, reach 100%.[3,4] Therefore, correctly assessing the severity of the illness to predict the mortality and morbidity of patients with necrotizing fasciitis is essential.

Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scores are calculated using the worst physiological variables, which were collected within the first 24 h of admission to the intensive care unit (ICU) and correlated to the highest number of points.[5,6] Unlike APACHE II and SAPS II systems, Sequential Organ Failure Assessment (SOFA) was designed to approximately estimate mortality risk, e.g., SOFA score between 0 and 6 denoted a mortality risk of <10%, whereas that between 15 and 24 predicted a mortality risk of >90%.[7,8] The Mortality in Emergency Department (MEDS) score has been 383

Yaşar et al. Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

validated as a predictor of 28-day mortality in patients who present to the emergency department (ED) with systemic inflammatory syndrome.[9]

of ICU admission, duration of hospitalization, and scores of the scoring systems among all patients and among survivors were analyzed.

According to a Medline research, the APACHE II system was the severity score most often used for necrotizing fasciitis,[10–13] whereas the SOFA and SAPS systems was less often used to predict mortality in patients with necrotizing fasciitis,[14] with the MEDS scoring system never being used.

Furthermore, no study has compared the scoring systems for predicting the mortality in patients with necrotizing fasciitis. Thus, this retrospective study compared the APACHE II, SOFA, SAPS, and MEDS scoring systems for predicting mortality and their correlation with hospitalization duration.

RESULTS

MATERIALS AND METHODS The study protocol was approved by the local ethical committee.

The APACHE II, SOFA, SAPS II, and MEDS scores were calculated on the basis of the worst laboratory values and clinical findings recorded during the first 24 h of admission to the ICU using online calculators available at the following links: http:// clincalc.com/IcuMortality/APACHEII.aspx, http://clincalc.com/ IcuMortality/SOFA.aspx, http://clincalc.com/IcuMortality/SAPSII.aspx, and http://emcalculator.com/meds, respectively.

Statistical Analysis The medical reports of 98 patients who presented with necrotizing fasciitis between January 2008 and December 2015 were retrospectively examined. The diagnosis of necrotizing fasciitis was confirmed by surgical exploration and pathological analysis of debrided tissues in all patients. Of all patients, 74 with available data were included in the study. Statistical analysis was performed using the SPSS software program version 21 (SPSS Inc., Chicago, IL). Because the differences between mortality rates estimated by different scoring systems were too wide and because the SOFA scoring system estimates mortality rates in ranges, we categorized patients into the following four groups according to estimated mortality rates: group 1, estimated mortality rates of <10%; group 2, estimated mortality rates between 10% and 29%; group 3, estimated mortality rates between 30% and 49%; and group 4, estimated mortality rates of ≥50%.

The ability of the scoring system to predict mortality was assessed by comparing estimated mortality rates in mortality groups (survivors/non-survivors) using chi-square test (Monte Carlo). After analyzing the ability of the scoring systems, mortality rates between survivors and non-survivors with estimated mortality rates of >10%, 30%, and 50% in the different scoring systems were compared in pairs by Pearson’s chisquare test. Furthermore, correlation between the duration 384

Patient characteristics, mortality rates, durations of ICU admissions, durations of hospitalization, and results of the scorings systems are all presented in Table 1.

Estimated mortality rates in the survivor and non-survivor groups were different for all the scoring systems, including APACHE II, SOFA, SAPS II, and MEDS (p<0.001, p<0.01, p<0.001, and p<0.01, respectively).

The actual mortality rates in the estimated mortality groups are presented in Table 2, which revealed that the predictions of the APACHE II and SAPS II scoring systems were closer to the actual mortality rates. Other than prediction accuracy, we also analyzed the predicted mortality rates as limits for mortality risk and presented the ratios of non-survivors to patients with predicted mortality rates of >10%, 30%, and 50% and the ratios of survivors to patients with predicted mortality rates of <10%, 30%, and 50% in Table 3.

The significant differences between the ratios of non-survivors to patients with predicted mortality rates of >10%, 30%, and 50% and the ratios of survivors to patients with predicted mortality rates of <10%, 30%, and 50% are presented in Tables 4 and 5, respectively.

There were no correlations between the scores of all the scoring systems (APACHE II, SOFA, MEDS, and SAPS II) and duration of hospitalization and duration of ICU admission among survivors (r=0.075, r=0.185, r=0.041, and r=0.201, respectively, and r=0.075, r=0.170, r=0.015, and r=0.143, respectively; p>0.05 for all).

Mortality rates and scores of the predictive scoring systems for patients with necrotized peritoneum and other sites, including abdomen, groin, lower limb, and breast, were not different (Table 6).

DISCUSSION Necrotizing fasciitis is uncommon but has a very high mortality and complication rate. In this study, the mortality rate was approximately the same as that recently reported.[4] However, the rate was greater than that predicted by the scoring systems. Severity scoring systems and mortality prediction have been developed for managing hospital resources and evaluating quality of care and therapeutic interventions; thus, the accuracy of these scoring systems is essential.

As observed in other studies, severity scores and estimated mortality rates in the survivor and non-survivor groups were Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

YaĹ&#x;ar et al. Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

Table 1. Patient demographic data, infection sites, comorbidities, estimated mortality rates, and actual mortality rates in patients with necrotizing fasciitis

n % p

Sex

Females

22

29.7

Males

52

70.3

Mortality

22 29.7

Site of infection

Perineum & genitalia

48

64.9

Abdomen & groin

20

27.0

Lower limb

5

6.8

Breast

1 1.4

Comorbidities

Diabetes mellitus

27

37.5

Coronary artery disease

18

25

Hypertension

13 18.1

Chronic kidney disease

4

5.6

Chronic obstructive pulmonary disease

3

4.2

Hematologic malignancy

4

5.6

Metastatic malignancies

14

19.4

Age

Median 25% 75% 57.5 43 66

LRINEC scores in survivors

5

3

7

LRINEC scores in nonsurvivors

5.5

2.75

9.5

Duration of ICU admission (all patients)

6

0

15.25

Duration of hospitalization (all patients)

17

10

27

Duration of ICU admission (survivors)

0

0

10

Duration of hospitalization (survivors)

17

10

26

APACHE II (all patients)

Severity score

9

4

15

(survivors)

Estimated mortality: %

9.9

5.1

22.3

(nonsurvivors)

Severity score

6.5

3

10

Severity score

16

11

22.5

SOFA (all patients)

Severity score

2

0

8

(survivors)

Estimated mortality: %

<10

<10

15â&#x20AC;&#x201C;20

(nonsurvivors)

Severity score

0.5

0

3

Severity score

5

2.75

7.25

SAPS II (all patients)

Severity score

30

21

41

(survivors)

Estimated mortality: %

10.6

4.2

26.6

(nonsurvivors)

Severity score

24

18.25

32.75

Severity score

39

30

48.5

MEDS (all patients)

Severity score

6

3

9

(survivors)

Estimated mortality: %

4.4

1.1

9.3

(nonsurvivors)

Severity score

3

0

7.5

Severity score

9

6

13.25

>0.05

<0.001

<0.001

<0.001

<0.001

P: The significance of the difference between survivors and non survivors. LRINEC: Laboratory Risk Indicator for Necrotizing Fasciitis; ICU: Intensive care unite; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; SAPS II: Simplified Acute Physiology Score II; MEDS: Mortality in Emergency Department.

different for all the scoring systems.[13,14] Because necrotizing fasciitis of the perineum and genitalia has a better prognosis than that of other body sites, we stratified the study by Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

comparing mortality rates and the scores of four scoring systems in patients with necrotizing fasciitis of the perineum and genitalia and other parts, including the abdomen, groin, lower 385

Yaşar et al. Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

Table 2. Actual mortality rates in estimated mortality groups Estimated mortality groups

APACHE II

SOFA

SAPS II

MEDS

Group 1

<10%

4/40 (10%)

15/65 (23.1%)

3/36 (8.3%)

17/68 (25%)

Group 2

10–29%

8/19 (42.1%)

5/7 (71.4%)

11/24 (45.8%)

0/1 (0%)

Group 3

30–49%

6/11 (54.5%)

0/0

4/10 (40%)

5/5 (100%)

Group 4

≥50%

4/4 (100%)

2/2 (100%)

4/4 (100%)

APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; SAPS II: Simplified Acute Physiology Score II; MEDS: Mortality in Emergency Department.

Table 3. Ratio of non-survivors to patients with predicted mortality rates of >10%, 30%, and 50% and that of survivors to patients with predicted mortality rates of <10%, 30%, and 50% Predicted mortality rates

APACHE II

SOFA

SAPS II

MEDS

≥10%

18/34 7/9 19/38 5/6

≥30%

8/11 2/2 8/14 5/5

≥50%

4/4 2/2 4/4

<10%

36/40 50/65 33/36 51/68

<30%

50/63 52/72 46/60 52/69

<50%

52/70 52/72 52/70 52/74

APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; SAPS II: Simplified Acute Physiology Score II; MEDS: Mortality in Emergency Department.

limb, and breast.[4] However, we did not observe any statistical difference, probably owing to late referrals to our clinic or severe comorbidities of the patients because our institution is a tertiary referral center.

Table 4. Comparisons of estimated mortality rate groups <10%, <30%, and <50% among survivors

APACHE II

SOFA

SAPS II

MEDS

APACHE II

n.s

**

n.s.

n.s n.s. n.s.

n.s * SOFA

n.s. n.s. n.s.

n.s. n.s. n.s.

n.s. n.s.

MEDS

n.s. n.s. n.s.

n.s. n.s. n.s.

SAPS II

**

n.s. n.s. n.s.

n.s.

n.s.

* n.s.

* p<0.05 significantly different. **p<0.01 very significantly different. ***p<0.001 extremely significantly different. APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; SAPS II: Simplified Acute Physiology Score II; MEDS: Mortality in Emergency Department; n.s.: Non-specific.

386

Our results showed that predicted mortality rates using the APACHE II and SAPS II scoring systems were more accurate than those using the SOFA and MEDS scoring systems. The median APACHE II score was 9.9, which was lower than that reported by Yilmazlar et al., which was 13.9; however, the mortality rate was also higher in their study (49%).[11] In contrast, the mean APACHE II score was 8.5 for survivors and 19.6 for non-survivors, and our results were close to those reported by Yilmazlar et al. (6.5 for survivors and 16 for nonsurvivors). The median SOFA and SAPS II scores were lower than those reported by Boyer et al. (30 vs. 37.2 and 2 vs. 4.7, respectively); similarly, the mortality rate in the current study was also lower (22% vs. 40.6%).[14] However, the mean SOFA and SAPS II scores for survivors and non-survivors were low in our study results (SOFA, 0.5 vs. 3 in survivors, 5 vs. 7.1 in non-survivors; SAPS II, 24 vs. 29.3 in survivors, 39 vs. 48.6 in non-survivors).

In this study, we assessed patients according to predicted mortality rates such as <10%, 10%–29%, 30%–49%, and ≥50%. Among patients with predicted mortality rates of <10%, APACHE II and SAPS II were the only scoring systems with accurate predicted mortality rates, whereas SOFA and MEDS underestimated the actual mortality rates. However, among patients with predicted mortality rates of >50%, the scoring systems underestimated the mortality, which was actually 100%. It was noteworthy that no patient had a predicted mortality rate of >50% in the MEDS scoring system.

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Yaşar et al. Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

Table 5. Comparison of mortality in estimated mortality groups ≥10%, ≥30, ≥50, respectively among nonsurvivors

APACHE II

SOFA

SAPS II

MEDS

APACHE II

n.s.

n.s.

n.s.

n.s. *** **

n.s. ***

SOFA

n.s. n.s. n.s.

n.s. n.s. n.s.

n.s. n.s.

MEDS

n.s. n.s. n.s.

** n.s. *

SAPS II

n.s.

*** n.s. n.s.

n.s.

n.s.

*** n.s.

p<0.05 significantly different. **p<0.01 very significantly different. ***p<0.001 extremely significantly different. APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; SAPS II: Simplified Acute Physiology Score II; MEDS: Mortality in Emergency Department; n.s.: Non-specific. *

Within the prediction widths of 10%–29% and 30%–49%, the estimated mortality rates of the SOFA and MEDS systems were much higher than the actual mortality rates, whereas those of the APACHE II and SAPS II systems were much closer to the actual mortality rates; when we combined these two prediction widths, the actual mortality rates were within the predicted mortality intervals, i.e., 10%–49% (46.6% and 44.1%, respectively).

Other than prediction accuracy, we also analyzed the predicted mortality rates as limits for mortality risk and observed that predicted mortality rates of APACHE II were superior to those of SAPS II. Therefore, we believe that it is reasonable to accept either APACHE II scores of >13 or 17 as a predictor of mortality, as suggested by Yilmazlar et al. or Suwantarat et al,, respectively.[10,11]

LRINEC scores of ≥6 may be associated with higher morbidity and mortality rates.[15,16] However, LRINEC scores in survivors and non-survivors were not different in the current study and thus could not be used for predicting the prognosis of necrotizing fasciitis in patients.

Although predicted and actual mortality rates may be different because of the limitation owing to items included, subjected to interpretation and influenced by factors, such as local admission, discharge, and management policies, we observed that the APACHE II and SAPS II scoring systems were superior for predicting the prognosis of necrotizing fasciitis in patients.

APACHE II was slightly superior to SAPS II when the predicted mortality rates as limits for mortality risks were compared in pairs. MEDS was originally designed to predict mortality in patients with sepsis at ED. It is considered to be more feasible for ED doctors than the other scoring systems because it has fewer parameters.[17] However, we believe that the MEDS scoring system underestimated the mortality rate because of the exclusion of Glasgow coma scale and biochemical parameters such as sodium, potassium, and creatinine levels and because only a small portion of our patients presented with sepsis. Conversely, SOFA focused on the assessment of organ dysfunction and morbidity whereas APACHE II and SAPS II are designed to predict mortality.[7,8] We believe that the strong feature of APACHE II and SAPS II is that they include Glasgow coma scale and vital parameters such as serum electrolytes levels. Another strong feature of these two scoring systems was the section regarding chronic diseases. Among our patients, the mortality rates were remarkably high among immunocompromized patients, particularly those with hematological malignancies who were prone to mortality.

Even if we included a high number of patients with necrotizing fasciitis in the current study, our results should be validated in multicenter studies with bigger sample sizes. Another limitation is that we did not include updated versions of some scoring systems, such as APACHE IV and SAPS III, in this comparative study.

In conclusion, four predictive scoring systems, namely

Table 6. Comparison of mortality rates and severity scores in the perineum, genitalia, and other body sites

Mortality rates

Perineum & genitalia

Other sites

p

15/48 (31.3%)

7/26 (26.9%)

>0.05

Median (25%–75%)

Median (25%–75%)

APACHE II scores

9 (4–17)

8 (1–22.5)

>0.05

SOFA scores

1.5 (0–5)

0.5 (0–5.5)

>0.05

SAPS II scores

30 (20–43)

29 (19.5–41.5)

>0.05

MEDS scores

6 (3–9)

6 (1.5–9)

>0.05

APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; SAPS II: Simplified Acute Physiology Score II; MEDS: Mortality in Emergency Department.

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Yaşar et al. Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

APACHE II, SOFA, SAPS II, and MEDS, had significantly higher predicted mortality rates for non-survivors than for survivors among patients with necrotizing fasciitis. All the scoring systems underestimated the mortality rates. However, APACHE II and SAPS II were relatively better in estimating mortality for patients with necrotizing fasciitis, although their accuracies remain limited. We believe that there is a requirement to develop a scoring system that is specific to necrotizing fasciitis. The APACHE scoring systems should currently be used rather than the other scoring systems.

Conflict of interest: None declared.

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16. Corbin V, Vidal M, Beytout J, Laurichesse H, D’Incan M, Souteyrand P, et al. Prognostic value of the LRINEC score (Laboratory Risk Indicator for Necrotizing Fasciitis) in soft tissue infections: a prospective study at Clermont-Ferrand University hospital. Ann Dermatol Venereol 2010;137:5–11.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Konvansiyonel skorlama sistemleri ile nekrotizan fasiitisli hastalarda mortaliteyi öngörebilir miyiz?

Dr. Necdet Fatih Yaşar,1 Dr. Mustafa Ufuk Uylaş,1 Dr. Bartu Badak,1 Dr. Uğur Bilge,2 Dr. Setenay Öner,3 Dr. Enver İhtiyar,1 Dr. Tarık Çağa,1 Dr. Ercüment Paşaoğlu1 1 2 3

Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Eskişehir Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Aile Hekimliği Anabilim Dalı, Eskişehir Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Eskişehir

AMAÇ: Bu araştırmada dört skorlama sisteminin (APACHE II, SOFA, SAPS II, MEDS) nekrotizan fasiitisli hastaların prognozlarını doğru tahmin etme yetenekleri karşılaştırıldı.

GEREÇ VE YÖNTEM: Nekrotizan fasiitis tanısı konulan yetmişdört hasta geriye dönük olarak değerlendirildi. Bu skorlama sistemlerinin mortalite tahmin yetenekleri, mortalite gruplarında (sağkalanlar ve ölenler) tahmin edilen mortalite oranları karşılaştırılarak ve ayrıca sağkalanlar ile ölen hastalar arasında mortalite oranları sırasıyla %10, %30 ve %50’nin üzerinde tahmin edilenlerde gerçek mortalite oranları ikili gruplar halinde karşılaştırılarak değerlendirildi.

BULGULAR: Sağkalanlar ile ölen hastalar arasında tüm skorlama sistemlerinde tahmin edilen mortalite oranları farklıydı. APACHE II ve SAPS II’nin tahmini mortalite oranları gerçek mortalite oranlarına diğer skorlama sistemlerinkinden daha yakındı. Tahmini mortalite oranları mortalite riski için limit değer olarak analiz edildiğinde ise, APACHE II’nin mortalite tahmin yeteneği SAPS II’ninkinden daha üstündü.

TARTIŞMA: Değerlendirilmeye alınan bu skorlama sistemlerinin hepsinde tahmin edilen mortalite oranları, ölenlerde sağkalanlara kıyasla daha yüksekti ancak hepsi de gerçek oranların altında mortalite tahmininde bulundu. Ancak, göreceli olarak APACHE II ve SAPS II nekrotizan fasiitisli hastalarda mortalite tahmininde diğerlerine kıyasla daha üstündü. Mevcut skorlama sistemleri arasında APACHE II’nin kullanılması daha uygun görünmektedir.

Anahtar sözcükler: APACHE II; MEDS; nekrotizan fasiitis; SAPS II; SOFA. Ulus Travma Acil Cerrahi Derg 2017;23(5):383–388

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doi: 10.5505/tjtes.2016.19940

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ORIG I N A L A R T IC L E

Usefulness of FGSI and UFGSI scoring systems for predicting mortality in patients with Fournier’s gangrene: A multicenter study Orhan Üreyen, M.D.,1 Atahan Acar, M.D.,2 Uğur Gökçelli, M.D.,1 Murat Kemal Atahan, M.D.,2 Enver İlhan, M.D.1 1

Department of General Surgery, İzmir Bozyaka Training and Research Hospital, İzmir-Turkey

2

Department of General Surgery, İzmir Atatürk Training and Research Hospital, İzmir-Turkey

ABSTRACT BACKGROUND: This study aimed to evaluate the usefulness of Fournier’s gangrene scoring index (FGSI) and Uludag FGSI (UFGSI) for predicting mortality in patients with FG. METHODS: Patients who underwent treatment and follow-up in the A division department of general surgery at two education and research hospitals between January 2012 and December 2015 were evaluated for mortality-related factors. The sensitivities of FGSI and UFGSI scoring systems for predicting mortality-related factors and disease prognosis were evaluated. Patients were grouped as survivors (Group I) or non-survivors (Group II).

RESULTS: In total, 29 patients were included in the study. The mean age (±SD) was 51.52±13.36 years. The mortality rate was 20.6% (six patients). Bacterial growth was observed in wound cultures of 17 patients (58.6%). Of the patients with bacterial growth, 11 (47.8%) were in Group I and six (100%) were in Group II. The presence of bacterial growth was significantly associated with mortality (p=0.028). Fourteen patients (48.3%) had comorbid conditions. The number of comorbid conditions was related (p=0.049). FGSI and UFGSI scores were significantly higher in Group II than in Group I (p=0.002 and p=0.001, respectively). Among UFGSI parameters, extent of disease, body temperature, pulse rate, and HCO3 values were significantly higher in Group II than in Group I (p<0.05). The FGSI and UFGSI scoring systems had 100% sensitivity and 78.2% and 73.9% specificity, respectively, for predicting mortality.

CONCLUSION: The FGSI and UFGSI scoring systems are valuable for predicting mortality in patients with FG. The extent of the disease was an important prognostic parameter in this study. Whichever scoring system is used, we suggest the use of the extent of disease score in UFGSI. Keywords: Fournier’s gangrene; mortality; scoring system.

INTRODUCTION Fournier’s gangrene (FG) is a rare, necrotizing fasciitis of the perineal and genital area and is a life-threatening condition that requires emergency surgery. FG is rapidly progressive and leads to septic shock and death if not promptly treated.

Address for correspondence: Orhan Üreyen, M.D. İzmir Bozyaka Eğitim ve Araştırma Hastanesi, Genel Cerrahi A Bölümü, İzmir, Turkey Tel: +90 232 - 250 50 50 E-mail: drureyen@yahoo.com Submitted: 13.06.2016 Accepted: 24.01.2017

Ulus Travma Acil Cerrahi Derg 2017;23(5):389–394 doi: 10.5505/tjtes.2017.71509 Copyright 2017 TJTES

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[1] The basis of disease is colorectal, genitourinary, or other infections of the genital area. FG is currently encountered in any age group. However, its prevalence increases after the age of 50 years.[2] The disease is 10-fold more prevalent in males than in females. The lower prevalence in females is suggested to be associated with the fact that the female perineum easily drains through the vagina, thereby possibly preventing the development of the disease.[3,4]

FG has a high mortality rate, despite standard therapies that involve aggressive large debridements and the use of broadspectrum antibiotics.[5] The following three factors have been advocated to influence disease outcomes: disease-, patient-, and physician-related factors. Physician-related factors include aggressive surgical intervention and appropriate anti-biotherapy selection. Parameters such as age, body temperature, heart rate, and respiratory rate are patient-related factors.

The extent of disease is a disease-related factor.[6] 389

Üreyen et al. Usefulness of FGSI and UFGSI scoring systems for predicting mortality in patients with Fournier’s gangrene

No reliable tool for predicting FG severity is currently available; however, scoring systems can be used to accomplish this task. An ideal scoring system must simply provide clear and effective data regarding the patient and must also detect high complication and mortality rates.[5] In this regard, Laor et al.[7] described a FG severity index in 1995. Many authors have begun using this severity index. Approximately 15 years after that study, Yilmazlar et al.[6] developed the Uludag FGSI (UFGSI) by incorporating age and the extent of disease in the FGSI scoring system. Although other scoring systems have been discussed in the literature, FGSI and UFGSI are the two most widely accepted scoring systems.[5]

tors and disease prognosis. In addition, UFGSI parameters were separately evaluated. Patients were grouped as survivors (Group I) or non-survivors (Group II). Parameters and scores of FGSI and UFGSI scoring systems are shown in Table 1 (FGSI, A; UFGSI, A + B + C).[6] The parameters added to UFGSI were age (aged >60 years = 1 point, aged <60 years = 0 points) and extent of disease (FG confined to urogenital and/or anorectal area = 1 point, confined to pelvic area = 2 points, extended beyond pelvic area = 6 points).

Statistical Analysis The data were statistically analyzed using IBM SPSS Statistics version 22 software package. Fisher’s exact test was used to compare categorical data between the two groups. Mann– Whitney U test was used to compare the two groups if continuous variables showed non-parametric features. The optimum cutoff level of the power of the FGSI and UFGSI scoring systems for predicting mortality was calculated using an ROC analysis. ROC curves were created using IBM SPSS Statistics version 22 software package. AUC, sensitivity, specificity, positive likelihood ratio (LR), negative LR, positive predictive value (PV), negative PV, and confidence intervals for these values were calculated using the Med Calc demo version. A p value of <0.05 was considered to be statistically significant.

This study aimed to evaluate the usefulness of FGSI and UFGSI for predicting mortality in patients with FG.

MATERIALS AND METHODS Patients with FG who were treated and followed up at two education and research hospitals with high patient load between January 2012 and December 2015 were retrospectively reviewed. Age, sex, comorbid conditions, number of comorbid conditions, length of hospital stay, number of debridements, whether ostomy was performed or not, bacterial growth in wound culture, types of isolated bacteria, presence of diabetes mellitus (DM), and FGSI and UFGSI values were recorded. The sensitivities of the FGSI and UFGSI scoring systems were evaluated for predicting mortality-related fac-

RESULTS In total, 29 patients were included in this study. The mor-

Table 1. The Uludag Fournier’s gangrene severity index

+4 +3 +2 +1 0 +1 +2 +3 +4

a.

Physiological parameters Temperature (°C)

>41 39–40.9

Heart rate

>180 140–179 110–139

–

Respiratory rate

>50

35–49

–

Serum potassium (mmol/L)

>7

6–6.9

–

Serum sodium (mmol/L)

>180 160–179 155–159

Serum creatinine (mg/100 ml)

>3.5

2–3.4

1.5–1.9

38.5–38.9 36–38.4 34–35.9 32–33.9 30–31.9 <29.9 –

70–109

–

25–34

12–24

10–11

6–9

–

<5

5.5–5.9

3.5–5.4

3–3.4

2.5–2.9

–

<255

150–154 130–149 –

0.6–1.4

– –

55–69

40–54

120–129 110–119 <0.6

–

<39

<110 –

(X2 for acute renal failure)

Hematocrit (%)

>60 – 50–59 46–49 30–45 – 20–29 – <20

White blood count (X1000/mm )

>40

Serum bicarbonate, (venous (mmol/L)

>52

3

– 41–51

20–39.9 15–19.9 3–14.9 –

32–40

22–31

–

1–2.9

–

18–21

– 15–17

<1 <15

b.

Dissemination score Fournier’s gangrene confined to the urogenital and/or anorectal region, add “1” Fournier’s gangrene confined to the pelvic region, add “2” Fournier’s gangrene extending beyond the pelvic region, add “6” c. Age score Age ≥60 years, add “1” Age <60 years, add “0” Uludag Fournier’s gangrene severity index = a+b+c

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Table 2. Characteristics of the groups and related factors according to the mortality rate

Grup I

Grup II

Total

n (%)

n (%)

n (%)

P

Sex

Female

8 (34.8)

3 (50)

11 (37.9)

Male

15 (65.2)

3 (50)

18 (62.1)

0.646*

Stoma status

Yes

11 (47.8)

3 (50)

14 (48.3)

No

12 (52.2)

3 (50)

15 (51.7)

1.000*

Isolated bacteria type

Others

4 (36.4)

3 (50)

7 (41.2)

E. Coli

7 (63.6)

3 (50)

10 (58.8)

0.644*

Presence of bacteria in the culture

Yes

11 (47.8)

6 (100)

17 (58.6)

No

12 (52.2)

0 (0)

12 (41.4)

0.028*

Presence of diabetes mellitus

Yes

6 (26.1)

3 (50)

9 (31)

No

17 (73.9)

3 (50)

20 (69)

0.339*

Presence of additional disease

Yes

9 (39.1)

5 (83.3)

14 (48.3)

No

14 (60.9)

1 (16.7)

15 (51.7)

Mean±SD (min–max)

Mean±SD (min–max)

Mean±SD (min–max)

Age (years)

51.91±13.51 (31–78)

50±13.93 (29–68)

51.52±13.36 (29–78)

0.808**

Surgical debridements (number)

1.78±1.76 (1–9)

1.83±0.98 (1–3)

1.79±1.61 (1–9)

0.456**

Number of additional diseases

0.83±1.03 (0–3)

2±1.41 (0–4)

1.07±1.19 (0–4)

0.049**

26.35±25.07 (3–107)

11.5±10.56 (1–26)

11.5±10.56 (1–107)

0.118**

Length of the hospital stay (days)

0.080*

FGSI score

3.48±3.3 (0–11)

9.67±2.5 (7–14)

0.002*

UFGSI score

5.35±3.76 (1–14)

13.83±4.26 (9–20)

0.001*

Fisher’s exact test. **Mann-Whitney U test, FGSI: Fournier‘s gangrene severity index; UFGSI: Uludag Fournier’s gangrene severity index; SD: Standard deviation; Min: Minimum; Max: Maximum.

*

tality rate was 20.6% (six patients). Of all the patients, 11 (37.9%) were females and 18 (62.1%) were males. The mean age was 51.52±13.36 (range, 29–78) years. According to sex, the average age was 49 years for females and 53 years for males. There was no significant difference between the groups in terms of age and sex (p>0.05). Bacterial growth was observed in wound cultures of 17 patients (58.6%). Of all patients with bacterial growth, 11 (47.8%) were in Group I and six (100%) were in Group II. The most commonly encountered bacteria was Escherichia coli, which was present in 10 patients (58.8%), followed by Acinetobacter in two patients (11.8%) and Streptococcus, Staphylococcus aureus, Pseudomonas, Klebsiella, and Citrobacter each occurring in one patient (5.9%). The presence of bacterial growth in the cultures was significantly different between the two groups (p<0.05).

Fourteen patients (48.3%) had comorbid conditions. The mean number of comorbid conditions was 0.83±1.03 in Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Group I, 2.00±1.41 in Group II, and 1.07±1.19 in the whole study group. There was a significant difference between the groups in terms of the total number of comorbid conditions (p<0.05) (Table 2). The presence of DM, number of debridements, length of hospital stay, and other variables did not significantly differ between the two groups (p>0.05).

In the analysis of the FGSI and UFGSI scoring systems, FGSI and UFGSI scores were significantly higher in Group II than in Group I (p<0.05) (Table 1).

The extent of disease, body temperature, pulse rate, and HCO3 values were significantly higher in Group II than in Group I (p<0.05). The other variables did not significantly differ between the two groups (Table 3). The FGSI and UFGSI had 100% sensitivity and 78.2% and 73.9% specificity, respectively, for predicting mortality. ROC curves that were drawn 391

Üreyen et al. Usefulness of FGSI and UFGSI scoring systems for predicting mortality in patients with Fournier’s gangrene

Table 3. Parameters of between groups of mean and prognostic significance in FGSI and UFGSI scoring systems

Group I

Group II

p*

Mean±SD Min–Max Mean±SD Min–Max

Temperature (˚C) score

0.04±0.21

0–1

0.33±0.52

0–1

0.041

Heart rate score

0.35±0.78

0–2

2.17±0.41

2–3

0.0001

0±0

0–0

0.17±0.41

0–1

0.050

Serum K (mmol/L) score

0.13±0.34

0–1

0.67±1.21

0–3

0.204

Serum Na (mmol/L) score

0.09±0.42

0–2

0±0

0–0

0.610

Serum creatinine (mg/dL) score

0.91±1.47

0–4

1.5±1.76

0–4

0.390

Hematocrit (%x100) score

0.7±0.97

0–2

0.67±1.03

0–2

0.948

Respiratory rate score

0.65±0.78 0–2 1.17±0.41 1–2 0.086 White blood cell count (total/mm x1000) score 3

Serum bicarbonate (mmol/L) score

0.61±1.27

0–4

3.00±1.1

1–4

0.001

Dissemination score

1.57±1.08 1–6 3.83±2.4 1–6 0.014

Age score

0.3±0.47 0–1 0.33±0.52 0–1 0.893

Mann-Whitney U test. SD: Standard deviation; Min: Minimum; Max: Maximum.

*

Table 4. FGSI and UFGSI scoring systems for predicting mortality in patients with Fournier’s gangrene

Cut-off

FGSI score

>6

UFGSI score

>8

Sensitivity

Specificity

95% CI

95% CI

+ Likelihoodratio – Likelihoodratio + Predictivevalue 95% CI

95% CI

95% CI

95% CI

100

78.26

4.6

0

54.5

100

54.1–100.0 56.3–92.5 100

73.91

3.7–5.7 3.83

54.1–100.0 51.6–89.8

0 0

3.0–4.9

0

22.0–84.4 50 21.1–78.9

– Predictivevalue

81.5–100.0 100 80.5–100.0

FGSI: Fournier’s gangrene severity index; UFGSI: Uludag Fournier’s gangrene severity index.

according to the optimal cutoff values for predicting mortality (sensitivity, specificity, positive LR, negative LR, positive PV,

DISCUSSION

1.0

Sensitivity

0.8

0.6

0.4

0.4

0.0

Source of the curve FGSI UFGSI Reference Line

0.0

0.2

0.4

0.6

0.8

1.0

Figure 1. The predictive values of FGSI and UFGSI scoring systems were evaluated using ROC curve analysis.

392

and negative PV) in the FGSI and UFGSI scoring systems are presented in Table 4 and Figure 1.

FG is a rapidly progressive, infective, necrotizing fasciitis that is characterized by thrombosis and necrosis of subcutaneous tissues and superficial vessels in the perineal, genital, or perianal area.[8] The mortality rate is as high as 7.5%–40%, despite advances in medicine and technology.[8–10] The mortality rate was reported to be 7.5% by Sorensen et al.[11] and 16% by Eke et al.[3] in a review of 1726 patients. The mortality rate was 20.6% in this study, which was consistent with that reported in the literature. Many factors have been reported to influence mortality. Female sex has been advocated to be a risk factor for high mortality rates.[4,12] In this study, FG resulted in the death of 27% of females and 16.6% of males, showing higher mortality rate in females. Consistent with other studies, sex did not affect mortality.[4,13] Age is another concern that is discussed as a factor that affects mortality.[5,14,15] The present study did not report any association between age and mortality, similar to that reported

by Marin et al.[14] Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Üreyen et al. Usefulness of FGSI and UFGSI scoring systems for predicting mortality in patients with Fournier’s gangrene

Many other studies have investigated the role of comorbid conditions in mortality. In this regard, very few parameters have been suggested to have a significant role.[5,14] As one of the factors discussed, DM was present in nine patients (31%) in this study. Of the patients who died, 50% had DM in Group II and 26.1% had DM in Group I. Although the prevalence of DM was high in the high mortality group, as observed in other studies, DM had no effect on mortality.[5,6,14] In the current study, although the presence of comorbid conditions did not affect mortality alone, the presence of more than one comorbid conditions significantly affected mortality. Among these comorbid conditions, malignancy was reported to be an independent risk factor for mortality.[12] However, in our patients, only one patient was diagnosed as having malignancy, and this patient case was in Group I. FGSI was developed by Laor et al.,[7] who used vital findings and some laboratory data to determine the severity and prognosis of FG in patients. In this scoring system, the mortality rate is 75% if FGSI is >9 points and the survival rate is 78% if FGSI is <9 points. However, Yilmazlar et al.,[6] who asserted that this classification has some drawbacks, added a dissemination score and age into this system to create a modified UFGSI scoring system. Different studies have compared the two classification systems and evaluated their strengths.[5,14] The present study evaluated the roles of these scoring systems for predicting mortality. Both scoring systems were found to be correlated to mortality. Both systems yielded 100% sensitivity in the analysis of sensitivity and specificity. The specificity was 78% for FGSI and 73% for UFGSI. Yilmazlar et al.[6] described the UFGSI scoring system and reported a sensitivity of 94% and specificity of 81% for UFGSI. Roghmann et al.[5] reported these figures to be 85% and 67% for UFGSI. In the abovementioned two studies, the sensitivity and specificity for FGSI were 65%–100% and 88%–67% , respectively. Czymek et al.[4] reported a sensitivity of 87% and a specificity of 77% for FGSI, whereas Laor et al.[7] reported a sensitivity of 75% and specificity of 78%. In another study by Yılmazlar et al.,[13] no survivor was reported among patients with UFGSI scores of ≥9 in a series of 120 cases. The cutoff values for FGSI and UFGSI were 7 and 9, respectively.

Six of 12 cases with a score of >7 for FGSI died, whereas six of 13 cases with a score of >9 for UFGSI died. Despite these high rates, we consider that lower mortality in these cases was associated with a prompt and effective treatment.

The present study evaluated the association with mortality using common parameters in the two scoring systems, and age and the extent of disease that are only included in UFGSI. Of the common parameters, heart rate, body temperature, and bicarbonates were significant. Serum creatinine, hematocrit, and potassium levels were related to mortality in some studies.[10,14] Roghmann et al.[5] reported an association between mortality and creatinine and hematocrit. As observed, all parameters included in FGSI and UFGSI were significant.

Therefore, the authors have begun evaluating different parameters such as albumin, alkaline phosphatase, cholesterol, Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

lactate dehydrogenase, platelet count, calcium, and magnesium.[16–18] However, the value of these parameters for predicting mortality is only hypothetical. In the present study, the parameters of age and the extent of disease different from FGSI in UFGSI were separately analyzed. Age was not related to mortality; however, the extent of disease was higher in Group II than in Group I. One study that explored the need to establish a new scoring system suggested the use of the extent of disease for predicting prognosis.[5] The treatment of FG is based on large debridement of the wound and drainage after removing necrotic tissues, using broad-spectrum antibiotics, and providing hemodynamic stability.[3,8] All patients underwent large debridement under general anesthesia, and prophylactic broad-spectrum anti-biotherapy was initiated. Anti-biotherapy was revised according to the results of the cultures. In this study, bacterial growth was observed in wound cultures of 58.6% of patients. In addition, bacterial growth was observed in all fatalities. E. coli was the most prevalent agent in 58.8% of patients. The type of isolated bacteria and their rates were similar to those reported in the literature.[5,8] The presence of bacterial growth in the culture was an important factor for mortality; this was independent of the bacteria type.

The extensiveness of debridement can be life-saving; however, the association between mortality and number of debridements remains debatable,[15] and many studies[14,19,20] found no association, similar to that observed in our study. The association between the presence of colostomy and mortality remains debatable.[14,18,19] Fourteen patients (48.3%) with FG in close proximity to the anal area and resulting in fecal contamination underwent fecal diversion to prevent infections, morbidity, and mortality. The study by Li et al.[18] advocated fecal diversion to reduce mortality. However, fecal diversion had no role in reducing mortality in our series, similar to the study by Ozturk et al.[19] We consider that fecal diversion must not be routinely performed in all patients but must only be performed in selected patients with a high risk for contamination owing to close proximity to the anal area.

Our study had some limitations. The study had a retrospective design and small sample size. However, there are no large series of patients with FG in the literature, and there are continuous case reports.[21]

Conclusion FG must be considered for abscesses that occur in the perianal, perineal, and genital area that can lead to high mortality if left untreated, although the symptoms may appear insignificant. Patients must be treated with maximum care, and an aggressive treatment approach must be adopted. FGSI and UFGSI are useful for predicting mortality associated with FG. In this study, age had no influence in the UFGSI scoring system. We assume that age is not an important prognostic fac393

Üreyen et al. Usefulness of FGSI and UFGSI scoring systems for predicting mortality in patients with Fournier’s gangrene

tor, considering the fact that FG often occurs in advanced age groups. The extent of disease was an important prognostic parameter. Whichever scoring system is used, we suggest the use of the extent of disease score in UFGSI. Conflict of interest: None declared.

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14. Marin AG, Fuentes FT, Ayuso MC, Lillo JAA, Ballesteros JCC, Lopez MP. Predictive factors for mortality in fournier’s gangrene: A series of 59 cases. Ciresp 2015;93:12–7.

15. Ulug M, Gedik E, Girgin S, Celen MK, Ayaz C. The evaluation of microbiology and Fournier’s gangrene severity index in 27 patients. International Journal of Infectious Diseases 2009;13:424–30.

16. Kuo CF, Wang WS, Lee CM, Liuand CP, Tseng HK. Fournier’s gangrene: ten-year experience in a medical center in northernTaiwan. J Microbiol Immunol Infect 2007;40:500–6.

17. Mallikarjuna MN, Vijayakumar A, Patil VS, Shivswamy BS. Fournier’s gangrene: current practices. ISRN Surgery 2012;2012:1–8.

18. Li YD, Zhu WF, Qiao JJ, Lin JJ. Enterostomy can decrease the mortality of patients with Fournier gangrene. World J Gastroenterol 2014;28:7950–4.

19. Ozturk E, Sonmez Y, Yilmazlar T. What are the indications for a stoma in Fournier’s gangrene? Colorectal Disease 2011;13:1044–7.

20. Benjelloun EB, Souki T, Yakla N, Ousadden A, Mazaz K, Louchi A, et al. Fournier’s gangrene: our experience with 50 patients and analysis of factors affecting mortality. World J Emerg Surg 2013;8:13.

21. Arena GD, Cammarota A, Musto P. Fournier’s gangrene complicating thrombocytopenia treated with steroids. Lancet 2014;383:1580.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Fournier gangrenli hastalarda mortalite tahmininde FGSİ ve UFGSİ skorlama sistemlerinin prediktif değeri: Çok merkezli çalışma Dr. Orhan Üreyen,1 Dr. Atahan Acar,2 Dr. Uğur Gökçelli,1 Dr. Murat Kemal Atahan,2 Dr. Enver İlhan1 1 2

İzmir Bozyaka Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir Atatürk Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir

AMAÇ: Fournier gangreni (FG) hastalığının mortalite tayininde Fournier gangreni skorlama indeksi (FGSİ) ve Uludağ FGSİ’lerinin (UFGSİ) prediktivitesini araştırmak amaçlandı.

GEREÇ VE YÖNTEM: İki eğitim ve araştırma hastanesi genel cerrahi kliniğinde Ocak 2012 ile Aralık 2015 tarihleri arasında FG nedeniyle takip ve tedavi edilen olgular mortalite ile ilişkili faktörler yönünden değerlendirildi. Mortalite ilişkili faktörler ve hastalık prognozunun tayini için FGSİ ve UFGSİ skorlama sistemlerinin duyarlılıklarına bakıldı. Olgular yaşayan (Grup I) ve mortalite görülen (GrupII) olarak gruplandırıldı.

BULGULAR: Toplam 29 olgu çalışmaya dahil edildi. Yaş ortalaması 51.52±13.36 idi. Mortalite oranımız %20.6 (6 olgu) idi. Olguların 17’sinde (%58.6) yara kültüründe üreme saptandı. Üreme olan olguların 11’i (%47.8) Grup I, 6’sı (%100) Grup II’de idi. Bakteri üreme varlığı mortalite açısından istatistiksel olarak anlamlı bulundu (p=0.028). On dört (%48.3) olguda ek hastalık varlığı mevcuttu. Ek hastalık sayısı mortalite ile ilişkili bulundu (p=0.049). Fournier gangreni skorlama indeksi ve UFGSİ puanları Grup II olgularda istatistiksel olarak anlamlı yüksek bulundu (sırasıyla p=0.002 ve 0.001). Uludağ Fournier gangreni skorlama indeksi skorlama parametrelerinden Grup II olgularda yaralanan alan, vücut ısısı, nabız sayısı ve HCO3 puanları Grup I olguların puanlarından istatistiksel olarak anlamlı yüksek bulundu (p<0.05). Fournier gangreni skorlama indeksi ve UFGSİ’nin mortalite tahminindeki sensitivitesi %100 iken, spesitifite oranları sırasıyla %78.2 ve 73.9 idi.

TARTIŞMA: Fournier gangreni mortalitesinin öngörüsünde FGSİ ve UFGSİ oldukça etkindir. Çalışmamızda hastalığın yayılımı prognozda önemli bir parametre olarak görüldü. Hangi skorlama sistemi kullanılırsa kullanılsın UFGSİ’deki hastalığın yayılım parametresi mutlaka her olguda kullanılmalıdır.

Anahtar sözcükler: Fournier gangreni; mortalite; skorlama sistemi.

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ORIG I N A L A R T IC L E

Managing endoscopic retrograde cholangiopancreatography-related complications in patients referred to the surgical emergency unit Osman Şimşek, M.D., Arife Şimşek, M.D., Sefa Ergun, M.D., Mehmet Velidedeoğlu, M.D., Kaya Sarıbeyoğlu, M.D., Salih Pekmezci, M.D. Department of General Surgery, İstanbul University, Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: The goal of this study was to present our experience in the management of endoscopic retrograde cholangiopancreatography-related complications in patients referred to our surgical emergency unit by various endoscopy centers.

METHODS: A retrospective investigation was conducted on the records of the 54 patients who were referred to our surgical emergency unit between October 2005 and January 2014 due to endoscopic retrograde cholangiopancreatography-related complications.

RESULTS: There were 25 and 29 female and male patients, respectively. Pancreatitis was the most common complication (38.8%).

Perforation (27.7%), infection (20.3%), and bleeding (12.9%) were the other complications. In 22.2% of cases, patients were died. The mortality rate was the highest in patients with perforation (40%). The mean age of the patients who were died due to complications was 75.9 years (range, 47–94 years). In total, 41.6% of the patients were died within the first week and 33.3% were died within the second week following ERCP. Nearly half of these patients had a cancerous disease (one had metastatic breast cancer, one had a gallbladder cancer, one had a duodenal cancer, and the other three had periampullary cancers) and 50% of the patients who died also had cardiopulmonary and/or cerebrovascular disorders.

CONCLUSION: Comprehending and managing the main risk factors can minimize complications; however, they would not be eliminated. Moderate and severe complications may increase the mortality rates, particularly in high-risk patients.

Keywords: Complication; endoscopy; ERCP; infection; pancreatitis; perforation.

INTRODUCTION Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic procedure performed for diagnosing and treating pancreatobiliary disorders. Due to potential complications, its role in making a diagnosis has been questioned.

It has been advised to prefer alternative diagnostic tools whenever possible.[1] Complication rates of ERCP usually range between 5% and 10%, with a 2.7% mortality rate.[2,3] Acute pancreatitis occurs in 1.3–15.1% of cases when ERCP

is performed and is the most common complication.[4] Its occurrence rate may be as high as 30% in high-risk patients undergoing certain high-risk procedures.[5] Bleeding, perforation, infection, and cardiopulmonary complications are other common complications.[3] Early diagnosis and appropriate intervention may decrease morbidity and mortality rates associated with complications.

Address for correspondence: Arife Şimşek, M.D. İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul, Turkey Tel: +90 212 - 414 20 00 E-mail: draksimsek@yahoo.com.tr

Previous studies have demonstrated potential risk factors for post-ERCP complications and possible methods for improving the safety of ERCP and reducing the mortality and morbidity rates associated with complications in patients.

[1–3] Early surgical consultation is one of these methods. The present study was conducted to evaluate the management of post-ERCP complications in patients referred to our surgical emergency unit by various endoscopy centers.

Submitted: 05.04.2016 Accepted: 16.01.2017

MATERIALS AND METHODS

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Case Selection Criteria A retrospective investigation was conducted on the records of patients who were referred to our surgical emergency unit 395

Şimşek et al. Managing ERCP-related complications in patients referred to the surgical emergency unit

between October 2005 and January 2014 due to ERCP- related complications. Fifty-four patients were enrolled; they all had at least one of the following four complications: postERCP pancreatitis (PEP), perforation, infection, and bleeding. Although hyperamylasemia can commonly develop after ERCP was performed, it does not necessarily suggest pancreatitis. This study did not include hyperamylasemia patients unless it was interpreted as a sign of pancreatitis. Three-fold elevation of amylase and/or lipase levels in the presence of intense abdominal pain (which developed a new or exacerbated) for at least 24 h and the requirement of hospitalization for more than one night and/or radiological findings of pancreatic inflammation were accepted as characteristics of PEP. Patients who had at least two of the above three criteria were included.[6] Patients with bleeding were included if they were hemodynamically unstable and/or had at least 3 g/ dl reduction in the hemoglobin level and/or required transfusion.[6] Perforation was diagnosed with abdominal contrastenhanced computed tomography (CECT), by visualization of contrast extravasation or peritoneal/retroperitoneal free air, and physical examination findings.

with bleeding. Abdominal CECT scans were obtained from 36 patients. Twelve of the 54 (22.2%) patients were died.

Statistical Analysis

All patients with perforation had abdominal pain. Ten patients were admitted in the first day after ERCP was performed, four were admitted two days after ERCP was performed, and one was admitted 24 days after ERCP was performed. Two of these patients were immediately taken to the operating room due to severe sepsis, while the other 13 patients underwent abdominal CECT. Nonsurgical management was preferred in six patients with periampullary duodenal microperforations. Cholecystectomy and T-tube drainage after common bile duct exploration were performed in three patients with common bile duct injury. We performed primary closure of the duodenal perforation (second part of the duodenum in its posteromedial wall) combined with duodenal drainage in one patient. The walled-off abscess secondary to the duodenal perforation was surgically drained in one patient.

Cystogastrostomy and cholecystectomy were performed in one patient with gastric perforation. Primary closure reinforced with an omental patch was preferred for afferent loop perforation in two patients by Billroth II gastrectomy. The thoracic esophageal perforation in one patient was treated with primary repair and tube thoracostomy. All patients received antibiotic therapy. Four patients who underwent surgical interventions and two patients who were conservatively managed succumbed due to overwhelming sepsis. One of the two patients who died under conservative management had a pancreatic head cancer (she was 79 years old), and the other had chronic obstructive pulmonary disease (she was 88 years old). The first patient died 20 days after ERCP was performed; she did not have any progression of disease as observed in repeat CT scans. The second patient died two days after ERCP was performed, without having a repeat CT scan.

One of the four patients who died despite surgical treatment was a 77-year-old man with duodenal perforation. The others were a 97-year-old woman with esophageal perforation,

The descriptive statistical analysis of data was done using Statistical Package of the Social Sciences (SPSS) 17.0 software (SPSS Inc., Chicago, USA).

Ethics Committee Approval As this was a retrospective study, we did not apply for ethical committee approval. This study was conducted in accordance with the Helsinki Declaration.

RESULTS There were 25 and 29 female and male patients, respectively.

Their mean age was 57.8 years (range: 20–94 years). Indications for performing ERCP were choledocholithiasis (n=33), periampullary cancer (n=10), biliary stricture (n=5), pancreatic cyst (n=2), gallbladder cancer (n=1), acute cholangitis due to liver metastasis (n=1), acute biliary pancreatitis (n=1), and chronic pancreatitis (n=1). Periampullary cancers comprised a pancreatic head cancer (n=6), cancer of the ampulla of Vater (n=2), duodenal cancer (n=1), and distal bile duct cancer (n=1). The distribution of indications for performing ERCP corresponding to post-ERCP complications are shown in Table 1. All procedures were performed for therapeutic purposes. Sphincterotomy was performed in 39 (72.2%) patients. Of 39 sphincterotomies, 22 (56.4%) were done using the precut technique. Therapeutic applications of ERCP according to complications are shown in Table 2.

Fifty-four patients suffered complications, and their distribution was as follows: pancreatitis (n=21), perforation (n=15), infection (n=11) and hemorrhage (n=7). There were signs and symptoms of acute abdomen in all patients, except in those 396

Abdominal pain and vomiting were the most common symptoms in patients with pancreatitis. Eighteen of them presented in the first day after ERCP was performed. Seventeen patients underwent abdominal CECT. One patient (4.76%) had a necrotizing disease. Conservative management was the first choice in all patients with pancreatitis. As all patients with biliary obstruction were successfully drained at the time of performing ERCP, routine antibiotic prophylaxis was not used, excluding the patient with a necrotizing disease. Antibiotics (usually Imipenem) were used only in patients with clinically and/or microbiologically verified infections. Laparoscopic cholecystectomy was performed in two patients prior to discharge. Two of twenty-one (9.5%) patients died from sepsis and acute respiratory distress syndrome. One of these two had a necrotizing disease and a Ranson’s score of 2. She was 90 year old and had a cancer of the ampulla of Vater.

The other patient was an 87-year-old man with a Ranson’s score of 3.

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Table 1. Indications for ERCP according to post-ERCP complications

Pancreatitis Infection Perforation Bleeding

Choledocholithiasis

14 4 11 4

Periampullary tumor

4 3 1 2

Biliary stricture

3

2

Pancreatic cyst

2

Gallbladder tumor 1 Acute cholangitis due to liver metastasis

1

Acute biliary pancreatitis Chronic pancreatitis

1

1

ERCP: Endoscopic retrograde cholangiopancreatography.

Table 2. Procedures of endoscopic retrograde cholangiopancreatography according to complications

Pancreatitis Infection Perforation Bleeding

Sphincterotomy

16 2 4 3

Choledochal duct stenting

1

Sphincterotomy + Choledochal duct stenting

5 2

4

3 1

Sphincterotomy + Choledochal stenting + Biopsy

1

Sphincterotomy + Wirsung’s duct stenting

1

Sphincterotomy + Balloon dilation

1

1

Sphincterotomy + Stone removal

1

Stone removal 1 Cystogastrostomy 2 Failed procedure

1 1 3

a 68-year-old man with duodenal perforation (he had coronary heart disease), and a 47-year-old woman with duodenal perforation (she had metastatic breast cancer). None of the operated patients had surgical complications.

Patients with infection presented with abdominal pain, jaundice, and fever. Ten of them had cholangitis, and one had hepatic abscess. The patients with cholangitis were admitted to the ward in the first week after ERCP was performed, and the patient with hepatic abscess was admitted in the second week after ERCP was performed. As seven patients were referred by different endoscopy centers, it was not known if they had any infection prior to performing ERCP. However, it can be suggested that all had predisposing factors to infection (three patients had periampullary cancers and four had choledocholithiasis). All 11 patients received conservative management, including antibiotic treatment. Percutaneous drainage was performed in the patient with hepatic abscess.

Two patients died from sepsis. One of the patients who died had a pancreatic head cancer, and the other had a gallbladder cancer.

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performed. Additionally, biliary stents were inserted in four patients, and a biopsy sample was taken from one patient. Patients complicated with bleeding presented with melena and generalized weakness. Six of them were hospitalized on the first day after ERCP was performed. One patient was admitted 12 days after ERCP was performed. Two of them had a history of anticoagulant and antiplatelet therapies and elevated international normalized ratios (INRs) (1.48 and 1.68).

Six patients were conservatively managed, and one patient underwent laparotomy with hematoma evacuation. Laparotomy was performed in a patient with an INR of 1.68. Repeat endoscopy was performed in four patients (two had received an epinephrine injection and one had undergone additional sclerotherapy). Blood products were used in six patients.

Two of seven patients (28.5%) died. A 70-year-old woman who underwent surgery died from myocardial infarction, and a 76-year-old man who received conservative treatment died from febrile neutropenia. Febrile neutropenia was seen in a patient with a duodenal cancer.

The mean age of the patients who died was 75.9 years (range: 47–94 years). For the cause of death, 50% were among those 397

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with perforation, 16.6% were among those with pancreatitis, 16.6% were among those with infection, and 16.6% were among those with bleeding. Although pancreatitis was the most common complication (38.8%), its mortality rate (9.5%) was lower than that of other complications. The highest mortality rate was due to perforation (40%). Fifty percent of the patients who died had cancers (one had metastatic breast cancer, one had a gallbladder cancer, one had a duodenal cancer, and the other three had periampullary cancers). Further, 50% of those who died had cardiopulmonary and/or cerebrovascular disorders. For the time of death, 41.6% occurred within the first week and 33.3% occurred within the second week after ERCP was performed. The mean lengths of hospital stay were 7.58 (range: 2–18) and 15.9 (range: 4–86) days for fatal and nonfatal cases, respectively.

DISCUSSION ERCP is an endoscopic procedure performed for diagnosing and treating pancreatobiliary disorders. Complication rates of ERCP usually range between 5% and 10%, with a 2.7% mortality rate.[2,3] Several studies have reported that therapeutic procedures lead to more complications than diagnostic procedures. Halme et al. and Farrell et al. found complication rates of 9.1 vs. 1.8% and 4.6 vs. 2.1%, respectively.[7,8] The present study included a highly selected group of patients who were referred to a tertiary center surgical unit and who required rigorous management. It is therefore not surprising that all procedures were performed for therapeutic purposes, leading to more serious complications.

Acute pancreatitis (38.8%) was the most common complication after ERCP was performed. The mortality rate was the highest among patients with perforation, whereas it was the lowest among those with pancreatitis. These findings were consistent with those in the literature; however, the mortality rates were higher in the present study.[4,9] In a study on post-ERCP complications that prospectively investigated the survey data of 16,855 patients, the rate of ERCP-related complications (pancreatitis, bleeding, perforation, and infection) was 6.85%. Pancreatitis was the most common complication (50.6%), followed by infection (20.9%), bleeding (19.5%), and perforation (8.75%). Among the complicated cases, 24.4% were severe. The percentage of patients who were lost due to complications was 4.76%. Mortality rates in patients with pancreatitis, infection, bleeding, and perforation were as follows: 3.08%, 7.85%, 3.54%, and 9.9%, respectively.[9] In a review of post-ERCP-associated pancreatitis that pooled randomized controlled trial data from 13,296 patients, the incidence of PEP was 9.7% and the mortality rate was 0.7%.

The mortality rate of patients who were complicated with pancreatitis was 7.2%.[10] Some of the higher death rates in our study may be attributed to differences in the study design and inclusion criteria. The previous studies enrolled all patients who have undergone ERCP and included mild complications as well. There was heterogeneity in the descriptions 398

of complications. This study included patients referred to our surgical unit and in whom complications were either moderate or severe.

ERCP with sphincterotomy or ampullectomy is relatively contraindicated in patients with coagulopathy (INR >1.5 or platelet count <50,000/µL).[2,11] Our two patients with bleeding had a history of anticoagulant and antiplatelet therapy with elevated INRs. One of them underwent surgical intervention.

Post-ERCP-associated perforation was classified in descending order of severity into four types: type I, lateral or medial wall duodenal perforation; type II, perivaterian injuries; type III, distal bile duct injuries; and type IV, retroperitoneal air alone. Type IV injuries are not accepted to be indicative of true perforation and are thought to be related to compressed air used to maintain the patency of the duodenal lumen, which resulted in air passing within the duodenal wall.

Therefore, these types of perforations do not require surgical intervention. We preferred nonsurgical management in six patients with periampullary duodenal microperforation.

If nonsurgical intervention will be preferred in the management of perforation related with ERCP, repeated CECT scan should be planned.

The routine use of prophylactic antibiotics while performing elective ERCP is controversial. Current guidelines recommend prophylactic antibiotic therapy in all patients with cholangitis or biliary obstruction that is unlikely to be drained at the time when ERCP is being performed.[12] It was also recommended in immunocompromised patients and patients with communicating pancreatic cysts or pseudocysts before transpapillary or transmural drainage of pseudocysts.[13] Because patients enrolled in the present study were referred by different endoscopy centers, it was not known if they received prophylactic antibiotics prior to undergoing ERCP, and, besides, it was not known if patients with infection had any infections prior to undergoing ERCP. Because all cases of biliary obstruction were successfully drained at the time of performing ERCP, routine antibiotic prophylaxis was not used in patients with pancreatitis, except in the patient with a necrotizing disease. Antibiotics were used in patients with clinically and/or microbiologically verified infections. The immune system was compromised in six patients with a cancer, leading to death due to sepsis. Overwhelming sepsis was a major problem leading to death in the present study. We believe that bacterial overgrowth due to biliary stasis, even if it was successfully drained at the time of performing ERCP, increase the risk of infections, particularly in older patients with a tumor interfering with normal biliary drainage. Prophylactic antibiotics and, perhaps, even hospitalization can minimize potential complications.

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had a cancer that significantly decreased the chance of survival. Further, 50% of patients who died had cardiopulmonary and/or cerebrovascular disorders.

Because this was a retrospective study, it was limited by the records of patients. This study also was limited by the small number of patients.

Conclusion Understanding and managing the main risk factors can minimize complications; however, they would not be eliminated.

Moderate and severe complications may increase the mortality rate, particularly in high-risk patients. Potential benefits favor the use of therapeutic ERCP. Timely and effective intervention can reduce mortality and morbidity rates.

Conflict of interest: None declared.

REFERENCES 1. Cohen S, Bacon BR, Berlin JA, Fleischer D, Hecht GA, Loehrer PJ, et al.

National Institutes of Health state of the science conference statement: ERCP for diagnosis and therapy, January 14-16, 2002. Gastrointest Endosc 2002;56:803–9.

2. Freeman ML. Adverse outcomes of ERCP. Gastrointest Endosc 2002;56:273–82.

3. Anderson MA, Fisher L, Jain R, Evans JA, Appalaneni V, Ben-Menachem

T, et al. Complications of ERCP. Gastrointest Endosc 2012;75:467–73.

4. Koçak E, Filik L. Endoscopic retrograde cholangiopancreatography complications. Endoskopi Dergisi 2010;18:19–22.

5. Guda NM, Reddy DN, Kumar A. Complications of ERCP. Indian J Gastroenterol 2014;33:1–9.

6. Cotton P, Lehman G, Vennes J, Geenen J, Russell R, Meyers W, et al.

Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383–93.

7. Halme L, Doepel M, von Numers H, Edgren J, Ahonen J. Complications of diagnostic and therapeutic ERCP. Ann Chir Gynaecol 1999;88:127–31.

8. Farrell RJ, Mahmud N, Noonan N, Kellcher D, Keeling PW. Diagnostic and therapeutic ERCP: a large single centre’s experience. Ir J Med Sci 2001;170:176–80.

9. Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, et al. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol 2007;102:1781–8.

10. Kochar B, Akshintala VS, Afghani E, Elmunzer BJ, Kim KJ, Lennon AM, et al. Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc 2015;81:143–9.

11. Ferreira LE, Baron TH. Post-sphincterotomy bleeding: who, what, when, and how. Am J Gastroenterol 2007;102:2850–8.

12. Banerjee S, Shen B, Baron TH, Nelson DB, Anderson MA, Cash BD, et al. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 2008;67:791–8.

13. Cotton PB, Connor P, Rawls E, Romagnuolo J. Infection after ERCP, and antibiotic prophylaxis: a sequential quality-improvement approach over 11 years. Gastrointest Endosc 2008;67:471–5.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Bir acil cerrahi kliniğinin endoskopik retrograd kolanjiyopankreatografi komplikasyonları ile ilgili deneyimi Dr. Osman Şimşek, Dr. Arife Şimşek, Dr. Sefa Ergun, Dr. Mehmet Velidedeoğlu, Dr. Kaya Sarıbeyoğlu, Dr. Salih Pekmezci İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

AMAÇ: Bu çalışmanın amacı farklı endoskopi merkezleri tarafından kliniğimize yönlendirilen endoskopik retrograd kolanjiyopankreatografi (ERCP) komplikasyonları ile ilgili deneyimimizi aktarmaktır.

GEREÇ VE YÖNTEM: ERCP komplikasyonu nedeniyle Ekim 2005–Ocak 2014 tarihleri arasında acil cerrahi kliniğimize yönlendirilen 54 hastanın kayıtları geriye dönük incelendi.

BULGULAR: Çalışmada 25 kadın, 29 erkek hasta yer aldı. Pankreatit en sık görülen komplikasyon (%38.8) idi. Perforasyon (%27.7), enfeksiyon (%20.3) ve kanama (%12.9) diğer sık görülen komplikasyonlardı. En yüksek oran perforasyonlu hastalarda (%40) olmak üzere olguların %22.2’si ölüm ile sonuçlandı. Ölen olguların ortalama yaşı 75.9 idi (dağılım, 47–94). Ölümlerin %41.6’sı ERCP sonrası ilk hafta, %33.3’ü ikinci hafta içerisinde gerçekleşti. Ölen hastaların %50’sinde malign bir hastalık mevcuttu (birisinde metastatik meme kanseri, birisinde safra kesesi tümörü, birisinde duedonum tümörü, üçünde periampuller tümör). Ölen hastaların %50’sinde kardiyopulmoner ve/veya serebrovasküler hastalıklar da mevcuttu.

TARTIŞMA: Risk faktörlerini bilerek uygun yönetimin sağlanması komplikasyon oranını en aza indirse de tamamen ortadan kaldıramaz. Orta ve ciddi dereceli komplikasyonlar özellikle yüksek riskli hastalarda mortaliteyi artırabilir.

Anahtar sözcükler: Endoskopi; enfeksiyon; ERCP; komplikasyon; pankreatit; perforasyon.

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ORIG I N A L A R T IC L E

Fournier’s gangrene: A retrospective analysis of 25 patients Metin Yücel, M.D.,1 Adnan Özpek, M.D.,1 Fatih Başak, M.D.,1 Ali Kılıç, M.D.,1 Ethem Ünal, M.D.,1 Sema Yüksekdağ, M.D.,1 Aylin Acar, M.D.,1 Gürhan Baş, M.D.2 1

Department of General Surgery, Ümraniye Training and Research Hospital, İstanbul-Turkey

2

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

ABSTRACT BACKGROUND: Fournier’s gangrene is a surgical emergency that progresses rapidly and insidiously and results in high morbidity and mortality rates unless it is immediately diagnosed and managed. Here we analyze the outcomes of patients who were followed up and treated for Fournier’s gangrene.

METHODS: We conducted a retrospective analysis of the medical data of 25 patients operated on for Fournier’s gangrene between January 2010 and June 2015. The diagnosis of Fournier’s gangrene was made by performing a physical examination. Patients who had genital, perineal, and perianal tenderness; induration; cyanosis; gangrene; and subcutaneous crepitation were considered as having Fournier’s gangrene. Following resuscitation, aggressive surgical debridement was performed and vacuum-assisted closure (VAC) was conducted in addition to debridement in select patient. Repeat debridements were performed as requirement.

RESULTS: This study included 25 patients. Fourteen patients (56%) were females and 11 (44%) were males. The mean age of the patients was 54.3 years (range: 27–82 years). The mean duration of hospital stay was 21.4 days; the mean number of debridements performed was 2.4. Thirteen patients (52%) had perianal abscesses, and 20 (80%) had diabetes mellitus. All patients underwent extensive debridement; 16 patients (64%) underwent VAC in addition to debridement. Patients undergoing VAC had significantly longer durations of hospital stay and a higher mean number of debridements performed (p=0.004 and p=0.048, respectively). An ostomy was made in one patient, and one patient died.

CONCLUSION: In Fournier’s gangrene, early diagnosis, effective resuscitation, aggressive debridement, and VAC application in suitable cases may reduce the morbidity and mortality rates and the need for an ostomy.

Keywords: Aggressive surgical debridement; Fournier’s gangrene; vacuum-assisted closure.

INTRODUCTION Fournier’s gangrene is a necrotizing fasciitis disease affecting the genital, perianal, and perineal regions and causes extensive soft tissue necrosis by rapidly progressing between fascial planes, when its diagnosis and management are delayed. This emergency surgical condition is associated with a high mortality rate.[1–5] Urogenital and anorectal infections and trauma are the primary etiological factors of Fournier’s gangrene. It is often a polymicrobial condition caused by various aeroAddress for correspondence: Metin Yücel, M.D. Adem Yavuz Caddesi, No: 1, 34773 Ümraniye, İstanbul, Turkey Tel: +90 216 - 632 18 18 E-mail: drmetin69@mynet.com Submitted: 02.08.2016 Accepted: 12.01.2017

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bic and anaerobic micro-organisms.[2,6–12] Although Fournier’s gangrene is more common among men and the elderly, it may affect both sexes and every age group.[5,8,9,13] The basic principles of its management include broad-spectrum antibiotics and aggressive surgical debridement.[3,10] Despite advances in its diagnosis and treatment, the mortality rate due to Fournier’s gangrene remains as high as 16–50%.

[2,6,14–16] Here we analyze etiological and predisposing factors and outcomes associated with vacuum-assisted closure (VAC) in patients who were followed up and treated for Fournier’s gangrene over a 5-year period at our clinic, Umraniye Training and Research Hospital, Istanbul, Turkey.

MATERIALS AND METHODS We retrospectively reviewed the medical records of hospitalized patients operated on for Fournier’s gangrene at our clinic between January 2010 and June 2015. The diagnosis of Fournier’s gangrene was made by performing a physical examination. Patients with genital, perineal, and perianal tenUlus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Yücel et al. Fournier’s gangrene

Table 1. Impact of gender on outcome variables in patients with Fournier’s gangrene

Male Female p

Mean±SD Mean±SD

Age

42.0±9.8 63.9±10.7 0.0011

Number of debridements

2.4±1.0

2.4±1.6

0.7482

20.6±14.4

22.1±16.4

0.8001

performed Duration of hospital stay 1

t-test; 2Mann Whitney test. SD: Standard deviation.

software (IBM SPSS, USA). Variables were expressed as mean ± standard deviation (SD) or median (range), depending on their distribution. Categorical variables were expressed as frequencies and percentages. Fisher’s exact test was used for comparing continuous parametric variables. The t-test was used for the comparison of parametric variables with normal distribution. The Mann–Whitney U test was used for the comparison of parametric variables that lacked normal distribution. Statistical results were reported within 95% confidence interval. Differences were considered statistically significant when the p-value was less than 0.05.

RESULTS

derness; induration; cyanosis; gangrene; and subcutaneous crepitation were considered to have Fournier’s gangrene. The patients were admitted to the hospital ward, and resuscitation was initiated. Broad-spectrum antibiotics were administered.

The patients were operated on after they were stabilized and had provided informed consent. All infected necrotic tissues were debrided in the operation until the surgeon could observe living and bleeding tissues. The tissues were irrigated with hydrogen peroxide and povidone iodine during debridement. Repeat debridements were performed in patients with persistent infection and necrosis after the initial debridement.

In complicated cases with extensive and deep necrosis, VAC was performed together with second debridement. In contrast, in healed patients, the defect was closed with primary sutures or a graft.

Patient with secondary anorectal tumors, perianal abscesses, or simple skin infections without Fournier’s gangrene were not included. The demographic properties, predisposing factors, primary site of infection, number of debridements performed, number of patients who underwent VAC, and duration of hospital stay were analyzed.

Statistical Analysis Statistical calculations were performed using IBM SPSS 22

A total of 25 patients were enrolled. Among them, 14 (56%) were females and 11 (44%) were males. The mean age of the patients was 54.3±15.0 years (range: 27–82 years). The female patients had a significantly higher mean age (p=0.001).

The mean duration of hospital stay was 21.4±15.2 days (range: 4–55 days); the difference between females and males was not statistically significant (p=0.800). The mean number of debridements performed was 2.4±1.4 (range: 1–6); the difference between genders was not statistically significant (p=0.748) (Table 1).

The etiological factor was a perianal abscess in 13 patients (52%). When the patients with and those without a perianal abscess were compared for the mean duration of hospital stay and the mean number of debridements performed, there was no statistical difference (p=0.401 and p=0.273, respectively) (Table 2). A urogenital infection was detected in four patients (16%); the etiology remained unclear in eight patients (32%).

Twenty patients (80%) had diabetes mellitus (DM). Diabetic and non-diabetic patients showed no statistical difference in the mean duration of hospital stay and the mean number of debridements performed (p=0.235 and p=0.720, respectively) (Table 3). Three patients (12%) were obese and two of them also had DM. Extensive aggressive debridement was performed in all pa-

Table 2. Comparison of patients who had perianal abscess and those who had non-perianal abscess

Perianal abscess n

%

Mean±SD

Non-perianal abscess n

%

p

Mean±SD

Age, 52.4±12.8 56.3±17.5 0.5231 Gender Male

6

55

5

45

Female

7

50

7

50

1.0002

Number of debridements performed

2.7±1.6

2.2±1.1

0.2731

Duration of hospital stay

18.9±14.3

24.2±16.4

0.4011

1

t-test; 2Fisher’s exact test. SD: Standard deviation.

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Table 3. Impact of diabetes mellitus on outcome variables in patients with Fournier’s gangrene

perianal and sphincter involvement. One VAC patient (4%) who had a perianal abscess and DM died.

Diabetic Non-diabetic p

DISCUSSION

Mean±SD Mean±SD

Age

56.3±15.0 46.2±13.7 0.1841

Early diagnosis is central to the successful treatment of Fournier’s gangrene and a favorable prognosis. Although radiological techniques such as X-rays, ultrasonography, computed tomography, and magnetic resonance imaging are helpful for making a diagnosis, Fournier’s gangrene is typically diagnosed by performing a physical examination.[13,14,17,18] Pain, inflammation, edema, necrosis, and subcutaneous crepitation are often noted in the involved region upon performing a physical examination. Fournier’s gangrene was diagnosed by performing a physical examination in our study.

Number of debridements

2.4±1.4

2.6±1.5

0.7202

23.6±16.1

13.0±7.3

0.2352

performed Duration of hospital stay 1

t-test; 2Mann-Whitney test. SD: Standard deviation.

Table 4. Comparison of patients who underwent VAC and those who did not undergo VAC

VAC

Without VAC

Mean±SD Mean±SD

Age

55.0±13.9 53.0±17.7 0.7571

Number of debridements

Although Fournier’s gangrene may affect both sexes and occur at any age, it is more common among men and the elderly.[5,6,9,13] The reason for its decreased prevalence in women is explained by the simpler drainage of the female perineum via the vaginal route. Furthermore, many reports on this condition have been published by urology clinics in which men predominated in samples, which led to males being over-represented in reports. A study by Eke focused on 1726 patients with Fournier’s gangrene; the author found that the condition was 10 times more common in men.[7] The reason for the higher incidence of Fournier’s gangrene among the elderly may be increased susceptibility to the disease due to a weakened immune response secondary to chronic disorders and an increased prevalence of circulatory disturbances due to more common vascular pathologies at advanced ages.

Women were more numerous than men in our study; the female-to-male ratio was 1.27, and the mean age of our patients was 54.3 years.

p

2.8±1.5

1.7±0.7

0.0482

26.4±14.5

12.6±12.7

0.0042

performed Duration of hospital stay

1 t-test; 2Mann-Whitney test. VAC: Vacuum assisted closure; SD: Standard deviation.

tients (Fig. 1). VAC was added to debridement in 16 patients (64%). The mean duration of hospital stay was 26.4±14.5 days (range: 8–55) in patients who underwent VAC and 12.6±12.7 days (range: 4–44) in those who did not. The mean number of debridements performed was 2.8±1.5 (range: 1–6) in patients who underwent VAC and 1.7±0.7 (range: 1–3) in those who did not. Patients who underwent VAC had a significantly longer mean duration of hospital stay and higher mean number of debridements performed (p=0.004 and p=0.048, respectively) (Table 4).

DM, obesity, cancer, alcoholism, advanced age, poor hygiene, malnutrition, trauma, liver disease, renal failure, and other conditions suppressing immune functions are predisposing factors for Fournier’s gangrene.[2,3,12,19,20] Among these factors, DM is the most common.[2,4,6,7,9,12,13,15] Diabetes leads to increased susceptibility to infections owing to the suppression

One patient (4%) required an ostomy because of extensive

(a)

(b)

Figure 1. A patient who had Fournier gangrene (a) and aggressive surgical debridement (b).

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of chemotaxis, phagocytosis, and immune functions. Most of our study population (80%) was diabetic.

Etiological factors for Fournier’s gangrene include perineal, urogenital, and anorectal disorders as well as surgical interventions in these regions. Fournier’s gangrene may also develop due to the spreading of an abdominal or retroperitoneal infection. In women, infections in the episiotomy region during the postpartum period may also cause Fournier’s gangrene. Many studies have shown that perianal infections are the most common etiological factor in Fournier’s gangrene.

[2,6,9,11,14] In our study, 52% of the patients had a perianal origin, and 16% had a urogenital origin; no clear etiology could be revealed in 32% of the patients due to the lack of records.

An effective resuscitation, wide-spectrum antibiotherapy, and aggressive debridement of necrotic tissues form the foundation of successful therapy.[3,7,8,10] All necrotic and infected tissues should be debrided until healthy tissues can been observed. In patients in whom a single attempt of debridement was unsuccessful, repeat procedures should be performed until the infection is brought under control. According to the literature data, the required number of debridements ranges from 3.1 to 7.3.[2,6,14] The mean number of debridements performed in our study was 2.4.

Using VAC for Fournier’s gangrene provides efficient wound care, reduces edema, augments blood flow, and hastens tissue healing. It is comfortable for patients and decreases pain and the required number of wound dressings. VAC enables more comfortable mobilization and reduces the duration of hospital stay.[4,12,21–23] We performed VAC in addition to debridement in 64% of our patients. The mean duration of hospital stay was 26.43 days in our cohort, and the mean number of debridements performed was 2.81 in patients who underwent VAC. These numbers were higher than those in patients who did not undergo VAC. This finding is likely associated with the increased complexity of patients in whom VAC was performed.

There is no general consensus for performing colostomy in Fournier’s gangrene. Some authors have recommended performing colostomy in case of extensive sphincter involvement, colonic or rectal perforation, or large perineal wounds.

[2,6,9–11,15,24] In our study group, performing colostomy was necessary in only one patient due to extensive perianal and sphincter involvement. The low rate of colostomy in our series was attributed to the extensive use of VAC, particularly in complicated cases. We believe that an ostomy should be made in select patients for managing Fournier’s gangrene.

The prognosis of Fournier’s disease depends on its early diagnosis and treatment. Delays in the diagnosis and treatment, primary anorectal disease, advanced age, female gender, DM, malignant disorders, multiple organ failure at admission, and a high Fournier’s gangrene index are predictors of a poor progUlus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

nosis.[3,12,20] Despite advances in its diagnosis and treatment, the mortality rates associated with Fournier’s gangrene remains as high as 16–50%.[2,6,10,14] Unfortunately, a 70-year-old woman with a perianal abscess and diabetes died in our study.

In our opinion, the low mortality rate in our patients was due to performing aggressive surgical debridement and VAC. As our study was retrospective, some patient data could not be accessed, which did not allow the calculation of the Fournier gangrene’s index. In some patients, we were also unable to determine etiological and predisposing factors. These factors constitute the limitations of our study.

In conclusion, Fournier’s gangrene is a surgical emergency that develops acutely and progresses rapidly and insidiously. It is associated with pronounced morbidity and mortality rates when its diagnosis and management are delayed. We found that effective resuscitation, aggressive surgical debridement, and VAC in suitable cases provide controlled wound care and reduce morbidity and mortality rates and the need for an ostomy.

Funding The authors declared that this study was not funded by any company or person.

Informed Consent Informed consent was obtained from all patients.

Conflict of interest: None declared.

REFERENCES 1. Geraci G, Pisello F, Lupo F, Cajozzo M, Sciume C, Modica G. Fournier’s gangrene: case report and review of recent literature. Ann Ital Chir 2004;5:97–106.

2. Canbaz H, Caglikülekci M, Altun U, Dirlik M, Türkmenoglu O, Tasdelen B, et al. Fournier’s gangrene: analysis of risk factors affecting the prognosis and cost of therapy in 18 cases. Ulus Travma Acil Cerrahi Derg 2010;16:71–6.

3. Taviloglu K, Cabioglu N, Cagatay A, Yanar H, Ertekin C, Baspinar I, et al. Idiopathic necrotizing fasciitis: risk factors and strategies for management. Am Surg 2005;71:315–20.

4. Oguz A, Gümüş M, Turkoglu A, Bozdag Z, Ülger BV, Agacayak E, et al.

Fournier’s Gangrene: A summary of 10 years of clinical experience. Int Surg 2015;5:934–41.

5. Erdogan A, Aydogan I, Senol K, Uckan EM, Ersoz S, Tez M. Simple scoring system for prediction of mortality in Fournier’s gangrene. Eur J Trauma Emerg Surg 2016;42:513–8.

6. Oymacı E, Coskun A, Yakan S, Erkan N, Ucar AD, Yıldırım M. Evaluation of factors affecting mortality in Fournier’s Gangrene: Retrospective clinical study of sixteen cases. Ulusal Cer Derg 2014;30:85–9.

7. Eke N. Fournier’s gangrene: a review of 1726 cases. Br J Surg 2000;87:718–28.

8. Smith GL, Bunker CB, Dinneen MD. Fournier’s gangrene. Br J Urol 1998;81:347–55.

9. Korkut M, Icoz G, Dayangac M, Akgün E, Yeniay L, Erdogan O, et al.

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Dis Colon Rectum 2003;46:649–52.

17. Heiner JD, Baldwin K, Laselle B. Fournier gangrene: rapid diagnosis with bedside ultrasonography. CJEM 2010;12:528–9.

10. Yanar H, Taviloglu K, Ertekin C, Guloglu R, Zorba U, Cabioglu N, et al.

Fournier’s gangrene: risk factors and strategies for management. World J Surg 2006;30:1750–4.

18. Levenson RB, Singh AK, Novelline RA. Fournier gangrene: role of imaging. Radiographics 2008;28:519–28.

11. Morpurgo E, Galandiuk S. Fournier’s gangrene. Surg Clin North Am 2002;82:1213–24.

19. Norton KS, Johnson LW, Perry T, Perry KH, Sehon JK, Zibari GB. Management of Fournier’s gangrene: an eleven year retrospective analysis of early recognition, diagnosis, and treatment. Am Surg 2002;68:709–13.

12. Czymek R, Schmidt A, Eckmann C, Bouchard R, Wulff B, Laubert T, et al. Fournier’s gangrene: vacuum-assisted closure versus conventional dressings. Am J Surg 2009;197:168–76.

20. Sorensen MD, Krieger JN, Rivara FP, Klein MB, Wessells H. Fournier’s gangrene: management and mortality predictors in a population based study. J Urol 2009;182:2742–7.

13. Mallikarjuna MN, Vijayakumar A, Patil VS, Shivswamy BS. Fournier’s gangrene: Current Practices. ISRN Surg 2012;2012:937–42.

21. Assenza M, Cozza V, Sacco E, Clementi I, TarantinoB, Passafiume F, et al. VAC (Vacuum Assisted Closure) treatment in Fournier’s gangrene: personal experience and literature review. Clin Ter 2011;162:1–5.

14. Benjelloun EB, Souiki T, Yakla N, Ousadden A, Mazaz K, Louchi A, et al. Fournier’s gangrene: our experience with 50 patients and analysis of factors affecting mortality. World J Emerg Surg 2013;8:13.

15. Yılmazlar T, Isık O, Ozturk E, Ozer A, Gulcu B, Ercan I. Fournier’s gangrene: Review of 120 patients and predictors of mortality. Ulus Travma Acil Cerrahi Derg 2014;20:333–7.

16. Furr J, Watts T, Street R, Cross B, Slobodov G, Patel S. Contemporary trends in the inpatients management of Fournier’s gangrene: Predictors of length of stay and mortality based on population-based sample. Urology 2017;102:79-84.

22. Ozturk E, Ozguc H, Yılmazlar T. The use of vacuum assisted closure therapy in the management of Fournier’s gangrene. Am J Surg 2009;197:660–5.

23. Cuccia G, Mucciardi G, Morgia G, Stagno d’Alcontres F, Gali A, Cotrufo S, et al. Vacuum-assisted closure for the treatment of Fournier’s gangrene.

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24. Yan-Dong L, Wei-Fang Z, Jian-Jun Q, Jian-Jiang L. Enterostomy can decrease the mortality of patients with Fournier gangrene. World J Gastroenterol 2014;20:7950–4.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Fournier gangreni: 25 hastanın geriye dönük analizi Dr. Metin Yücel,1 Dr. Adnan Özpek,1 Dr. Fatih Başak,1 Dr. Ali Kılıç,1 Dr. Ethem Ünal,1 Dr. Sema Yüksekdağ,1 Dr. Aylin Acar,1 Dr. Gürhan Baş2 1 2

Ümraniye Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

AMAÇ: Fournier gangreni akut gelişen, hızlı ve sinsi ilerleyen, tanı ve tedavide geç kalındığında yüksek oranda morbidite ve mortalite ile sonuçlanan acil cerrahi bir hastalıktır. Bu çalışma ile kliniğimizde Fournier gangreni tanısı ile takip ve tedavi edilen hastaların sonuçlarını irdelemeyi amaçladık.

GEREÇ VE YÖNTEM: Bu çalışma, 2010–2015 yılları arasında Fournier gangreni tanısıyla ameliyat edilen hastaların geriye dönük taranması ile yapıldı.

Hastaların tanısı fizik muayene ile konuldu. Genital, perineal ve perianal bölgede hassasiyet, endurasyon, siyanoz, gangren ve cilt altı krepitasyon saptanan olgular Fournier gangreni olarak kabul edildi. Resussitasyonu takiben agresif cerrahi debritman ve seçilmiş olgularda debritmana ilave olarak ‘Vacuum Assisted Closure’ (VAC) uygulandı. Gerekli durumlarda mükerrer debritmanlar yapıldı. Hastaların takip ve tedavi sonuçları analiz edildi.

BULGULAR: Çalışmaya 25 hasta dahil edildi. Bunlardan 14’ü (%56) kadın, 11’i (%44) erkek olup yaş ortalaması 54.3 (dağılım, 27–82) idi. Kadınların yaş ortalaması istatistiksel olarak daha yüksekti (p=0.001). Hastanede ortalama yatış süresi 21.4 gün, ortalama debritman sayısı 2.4 kez idi. Hastaların 13’ünde (%52) perianal bölgede apse ve 20’sinde (%80) diabetes mellitus tespit edildi. Hastaların tümünde geniş debritman, 16’sında (%64) ise debritmana ilave olarak VAC uygulaması yapıldı. VAC uygulanan hastalarda hastanede ortalama yatış süresi ve ortalama debridman sayısı istatistiksel olarak daha yüksek bulundu (sırasıyla, p=0.004, p=0.048). Bir hastaya ostomi açıldı ve bir hasta mortal seyretti.

TARTIŞMA: Fournier gangreninde erken tanı, etkili resüsitasyon, agresif debritman ve uygun olgularda debritmana ilave olarak VAC uygulanması ostomi ihtiyacını, morbidite ve mortaliteyi azaltabilir.

Anahtar sözcükler: Agresif cerrahi debritman; Fournier gangreni; vakum yardımlı kapama.

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ORIG I N A L A R T IC L E

Primary exploration for radial nerve palsy associated with unstable closed humeral shaft fracture Soo-Hong Han, M.D., In Tae Hong, M.D., Ho Jae Lee, M.D., Sang June Lee, M.D., Uk Kim, M.D., Dong Won Kim, M.D. Department of Orthopaedic Surgery, CHA Bundang Medical Center, School of Medicine, CHA University, Seong-nam-Republic of Korea

ABSTRACT BACKGROUND: The treatment of radial nerve palsy caused by closed humeral shaft fracture is a matter of debate. The purpose of this study is to evaluate the outcome of early surgical management of radial nerve palsy in patients with unstable closed humeral shaft fractures and to determine whether patients with this injury should be surgically explored.

METHODS: Medical records of 15 consecutive patients who had undergone open reduction and internal fixation for unstable closed humeral shaft fractures were reviewed. Injury mechanisms, radiographs, intraoperative findings of the injured nerve, and clinical improvement were analyzed. Of the 15 patients, two were injured during simple falls, two during baseball pitching, one by a fall from a height, one during skiing, and one by direct machine impaction during work. Fracture locations were middle humerus in six patients, middle-distal in eight patients, and middle-proximal in one patient. Fracture patterns were transverse fracture in six patients, butterfly segment fracture in four patients, oblique segment fracture in three patients, and spiral fracture in two patients.

RESULTS: Eleven patients showed macroscopically intact nerves, and four had total nerve transection. All four patients with total nerve transection were injured in traffic accident. Of these four patients, one showed comminuted fracture with butterfly fragment on the middle-distal shaft and the other three showed displaced transverse fracture on the middle to middle-distal shaft area. Transected nerves were directly repaired in two patients. In the other two patients, humerus shortening and nerve grafting were performed because of mangled nerve endings. All patients who had intact nerves showed fully recovered function at the last follow-up.

CONCLUSION: For radial nerve palsy accompanied by unstable humeral shaft fracture, primary exploration of the radial nerve and open reduction and plate fixation of the fracture should be considered as a treatment of choice. High-energy trauma, fracture location at the middle-distal humerus, and simple transverse fracture or comminuted fracture with butterfly fragment seems to be risk factors for radial nerve transection.

Keywords: Humeral fracture; primary exploration; radial nerve palsy.

INTRODUCTION Radial nerve palsy is commonly accompanied with humeral shaft fracture. The overall incidence of radial nerve palsy after humeral shaft fracture is 11.8% according to the recent systematic review.[1] As radial nerve is relatively fixed anatomiAddress for correspondence: Soo-Hong Han, M.D. Department of Orthopaedic Surgery, CHA Bundang Medical Center, School of Medicine, CHA University, Seong-nam, Republic of Korea Seong-nam - South Korea Tel: (82)10-8668-0559 E-mail: hsoohong@hanmail.net Submitted: 01.05.2016 Accepted: 09.02.2017

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cally by spiral groove of the humeral shaft and lateral intermuscular septum of the arm, fracture at this level can easily damage the nerve.[2] The treatment of radial nerve palsy caused by the closed humeral shaft fracture is a matter of debate.[1,3] Some authors recommend early exploration of the radial nerve and open reduction and fixation of the fracture, whereas others advocate conservative treatment of the fracture and a strategy of expectant management for radial nerve palsy.[4–10] Korompilias et al. recommended 16–18 weeks of expectant management, followed by surgical intervention due to high rate of spontaneous recovery of radial nerve after closed humeral shaft fracture.[2] The treatment of closed humeral shaft fracture itself is controversial. There is no sufficient evidence available to ascertain whether surgical intervention of humeral shaft fractures results in a better or worse outcome than no surgery.[11] However, surgery is recommended in cases with unstable 405

Han et al. Primary exploration for radial nerve palsy associated with unstable closed humeral shaft fracture

fracture, >20° angulation anterior/posterior, >30° varus/ valgus, inability to maintain a reduction, floating elbow, and polytrauma.[12] Furthermore, due to improvement of surgical technique and implants, a marked increase in the surgical treatment of humeral shaft fractures was seen.[13] Therefore, for the treatment of radial nerve palsy associated with unstable closed humeral shaft fracture, early exploration of the radial nerve together with open reduction and internal fixation of the fracture may help confirm nerve injury on early stage and also prevent further nerve damage.

Although treatment is a controversial subject, certain principles of management must be applied. The purpose of this study is to evaluate the outcome of early surgical management of radial nerve palsy in patients with unstable closed humeral shaft fractures and to determine whether patients with this injury should be surgically explored.

Table 1. Radial nerve palsy in relation to injury mechanism Injury Traffic Simple Fall from Sports Direct mechanism accident fall height injury trauma 2 1 3 1 8 (4)*

Patients with complete nerve transection are shown in parentheses.

*

Table 2. Radial nerve palsy in relation to fracture location Fracture location

1

6 (1)*

8 (3)*

Patients with complete nerve transection are shown in parentheses.

Table 3. Radial nerve palsy in relation to fracture type

Medical records of 15 consecutive patients who had undergone open reduction and internal fixation for closed humeral shaft fractures between March 2001 and February 2012 were reviewed after institutional review board approval. Operative standards used for closed humeral shaft fractures are as follows: >20° angulation anterior/posterior, >30° varus/valgus, inability to maintain a reduction, floating elbow, and polytrauma.[12] Inclusion criteria for this study were closed humeral shaft fracture, complete motor and sensory deficit of radial nerve, age >20 at the time of injury, and follow-up period of at least 12 months.

406

Middle-distal

*

Fracture type

Of 15 patients, the most common cause of injury was by traffic accident in eight patients (five in car, two pedestrians, and one motorcycle). Two patients were injured by simple falls, two during baseball pitching, one by falling from a height, one during skiing, and one by direct machine impaction during work (Table 1). Fracture locations were middle humerus in six patients, middle-distal in eight patients, and middle-proximal in one patient (Table 2). Fracture patterns were transverse fracture in six patients, butterfly segment fracture in four patients, oblique segment fracture in three patients, and spiral fracture in two patients (Table 3).

Middle

MATERIALS AND METHODS

This study was conducted on 15 patients who had primary exploration for radial nerve and open reduction and plate fixation for closed humeral shaft fracture. Twelve male and three female patients with an average age of 39.8 years (20– 66 years) were included. The average follow-up period was 2.4 years (14 months-4 years). All 15 patients visited the emergency room, applied a U-slap splint, and had their X-rays taken. All cases were of unilateral fractures with no accompanying damage. Physical examination of the radial nerve was initially performed at the emergency room. Motor powers of the wrist and metacarpophalangeal joints extension and sensory of the first web space were assessed.

Middle-proximal

Transverse 6 (3)*

Butterfly

Oblique

Spiral

4 (1)* 3 2

Patients with complete nerve transection are shown in parentheses.

*

Surgery was performed after an average of 3 days after admission to the hospital. All cases were managed by open reduction and internal fixation with plates and screws, which would allow for direct fracture reduction and visualization of the radial nerve. Standard anterolateral approach was used in all cases. After dissecting the internervous plane between brachialis and brachioradialis, the radial nerve and fracture site were identified. The radial nerve was thoroughly explored using loupes. Meticulous technique was used so as not to damage the nerve. With the radial nerve in protection, reduction and fixation of the fracture was performed using 4.5-mm limited-contact dynamic compression plate (Synthes, West Chester, USA). In case of complete transection of the radial nerve, neurolysis and repair of the injured radial nerve was performed by epi-perineural suture technique using a monofilament (Ethicon Nylon black monofilament, 8–0).

Postoperatively, we applied long arm splint until 1–2 weeks.

Gentle progressive range of motion exercises was permitted just after the removal of the splint. We recommend wearing low-profile short arm braces for radial nerve palsy until motor power is recovered to grade >4.

Changes in symptoms were verified through observation at outpatient visits to the hospital. Based on data acquired through these observations, injury mechanisms, and intraoperative findings of nerve injury, clinical improvements (union, grip power, and wrist range of motion) at the last follow-up were evaluated. On radiographs, fracture location was analyzed. The three diaphyseal middle parts (middle-proximal, middle, and middle-distal) were included as shaft fractures in this study. Fracture patterns were also examined on the initial radiographs.

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Neurological examination was conducted using the medical research council neurological scale, and for motor function, wrist and digit extension at the metacarpophalangeal joint were evaluated.[14] Each follow-up observation was made during outpatient visits on postoperative 1 and 6 weeks, 3 and 6 months, and 1 and 2 years.

RESULTS Surgical exploration of the radial nerve was performed in all patients. Eleven patients showed macroscopically intact nerves (Fig. 1), and four underwent total nerve transection.

All four patients with total nerve transection were injured in traffic accident. Of these four patients, one showed comminuted fracture with butterfly fragment on the middledistal shaft and the other three patients showed displaced transverse fracture on the middle to middle-distal shaft area.

Transected nerves were directly repaired in two patients (Fig. 2). In the other two patients, humerus shortening and nerve grafting was performed because of mangled nerve endings.

All patients with intact nerves showed fully recovered function of wrist and finger extension at the metacarpophalangeal

(a)

(b)

joint at the last follow-up. The mean time to full functional recovery in patients with intact nerve was 5 months with a range of 1–9 months, whereas it was 13 months after surgery with a range of 12–15 months in patients with completely transected nerve. The mean time to fracture healing was 3 months with a range of 2–6 months. There was no acute or late complication, such as nonunion and infection, in all cases.

DISCUSSION In our study, complete nerve transection was found in 26.7% (4 out of 15) of all cases. Common fracture patterns and location in complete nerve transected patients were transverse fractures on the middle to middle-distal shaft in three patients and comminuted fracture with a butterfly fragment on the middle shaft in one patient (Table 4). Nerve injury was most commonly associated with high-energy trauma, and all patients with transected nerve were injured through traffic accidents. Our result also showed that all patients with radial nerve palsy associated with humeral shaft fracture fully recovered function at the final follow-up.

An anatomic cadaver study demonstrated that the radial

(c)

Figure 1. A 22-year-old injured in a motor vehicle accident with middle-distal transverse humeral shaft fracture. (a) Preoperative radiograph demonstrating displaced fracture on middle-distal humeral shaft. (b) Postoperative radiograph of patients who underwent open reduction and plate fixation. (c) Macroscopically intact radial nerve.

(a)

(b)

(c)

(d)

Figure 2. A 35-year-old inured in a motor cycle accident with humeral shaft fracture with middle butterfly fragment. (a) Preoperative radiograph demonstrating displaced fracture on middle-distal humeral shaft. (b) Postoperative radiograph of patients who underwent open reduction and plate fixation. (c) Intraoperative inspection of the radial nerve showed complete transection. (d) Neurolysis and perineural neurorraphy performed.

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Table 4. Radial nerve palsy in relation to Fracture location, type Location

Transverse Butterfly Oblique Spiral Total

Mid.-proximal 1 Middle Mid.-distal Total *

2 3 (3)* 6

0

0 0 1

1

3 0 6

3 (1)* 0 2 8 4

3

2 110

Complete nerve transection patient are shown in parentheses. Mid.: Middle.

nerve is at risk at two locations. These locations are the posterior midshaft, where the nerve lies in contact with the humerus, and the distal lateral humerus, where it pierces the lateral intermuscular septum.[15] In our study, middle-distal fracture was most common and fracture location of all cases with transected nerve were middle to middle-distal shaft area.

The optimal management strategy for radial nerve palsy in the setting of a humeral shaft fracture remains controversial. Shao et al. presented a systematic review of the literature.[1] Spontaneous recovery was documented in 315 of 435 patients with primary radial nerve palsy (RNP) (72%). Of the remaining 120 patients, 104 underwent late exploration at an adjusted mean time of 4.3 months, and 69% had postoperative recovery.

Overall, 89% of those initially treated non-operatively achieved functional recovery.

Potential advantages of an initial non-operative approach include the fact that RNP often resolves spontaneously and that it avoids the risk of complications that may occur with surgery.[16–18] Furthermore, proponents of an initial non-operative approach suggest that delaying surgical exploration does not affect the outcome and that surgical treatment is easier once the fracture has healed.[1] Many researchers have demonstrated that RNP after a humeral shaft fracture is usually caused by a nerve conduction block, and therefore, exploration of the nerve is unnecessary because spontaneous recovery is nearly always the rule.[4,19–21] In other studies, the rate of spontaneous RNP recovery among patients with humeral shaft fractures was quite impressive at 70%–89% for closed fractures and 71% for open fractures.[1,4,19] Because of this, most authors recommend an exploration in cases where there are no clinical signs of recovery after 4–6 months.[1,16,21] On the other hand, advocates of early exploration of the radial nerve report a variety of advantages. Early exploration is technically easier and safer than delayed procedure. Direct examination of the injured nerve clarifies the diagnosis and the extent of the lesion, and the risk of nerve envelopment by scar tissue decreases. Occasionally, there are patients with lacerated nerves for which the primary operation is likely the optimal occasion to assess the status and management of the nerve. Moreover, in patients without recovery of nerve function after the primary internal fixation without nerve explora408

tion, a later exploration involves a more technically demanding procedure in which the nerve could be embedded in callus.[22] Early exploration and expedient repair of a radial nerve laceration will result in a superior outcome to a delayed repair.

The review by Pollock et al. included both open and closed fractures and demonstrated that 68% of nerves with early exploration showed complete recovery. They noted nerve lacerations in 20%–42% of cases after late exploration, and they also noted poor results clinically after late repair.[6] Series with late exploration have revealed nerve laceration or entrapment to be present in 6%–25% of cases.[6,8,23,24] Subsequently, advocates for early exploration of an RNP with a simple closed humeral shaft fracture would argue that after consideration of the plethora of available series, including a number of series that have documented the risk of a nerve laceration or incarceration with a closed humeral shaft fracture to be as high as 25%, that expectant or delayed nerve exploration can compromise ultimate recovery. Prolonged observation of cases with a lacerated or incarcerated radial nerve will result in no nerve recovery, potential atrophy and motor endplate loss, compromised nerve recovery on late exploration and repair, and significant interval loss of patient function and livelihood.

[25] In contrast, early exploration and repair performed earlier can facilitate better characterization of the nerve injury, quicker nerve recovery on repair with less distal endplate loss, less muscular atrophy, quicker return to function, and emotional relaxation. Moreover, after fracture fixation and stabilization is achieved, a neurolyzed or repaired nerve will potentially benefit from a better environment for recovery with less tension, motion, or callus formation to impede nerve healing.[24,26] Recovery from RNP may be affected by several factors including the cause and extent of nerve injury and the location and type of fracture. Unfortunately, due to insufficient number of patients in the current study, we were unable to perform meaningful subgroup analyses to determine whether the outcome of initial management is affected by these factors.

Depending on several mechanisms and different fracture personalities, the possibility of radial nerve injury changes.

Therefore, we suggest that considering injury pattern, radial nerve palsy should be approached individually rather than in a uniform manner in closed humeral shaft fractures.

Conclusion For radial nerve palsy accompanied by unstable humeral shaft fractures, primary exploration of the radial nerve and open reduction and plate fixation of the fracture should be considered as a treatment of choice. High-energy trauma, middledistal humeral shaft fracture, and simple transverse fracture or comminuted fracture with butterfly fragment seem to be the risk factors for radial nerve transection. However, highquality, randomized case control studies are needed to clarify the risk factors and treatment efficacy.

Conflict of interest: None declared.

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REFERENCES 1. Shao YC, Harwood P, Grotz MR, Limb D, and Giannoudis PV. Radial nerve palsy associated with fractures of the shaft of the humerus: a systematic review. J Bone Joint Surg Br 2005;87:1647–52.

2. Korompilias AV, Lykissas MG, Kostas-Agnantis IP, Vekris MD, Soucacos PN, Beris AE. Approach to radial nerve palsy caused by humerus shaft fracture: Is primary exploration necessary? Injury 2013;44:323–6.

3. Ring D, Chin K, and Jupiter JB. Radial nerve palsy associated with highenergy humeral shaft fractures. J Hand Surg Am 2004;29:144–7.

4. Larsen LB and Barfred T. Radial nerve palsy after simple fracture of the humerus. Scand J Plast Reconstr Surg Hand Surg 2000;34:363–6.

5. Amillo S, Barrios RH, Martinez-Peric R, Losada JI. Surgical treatment of the radial nerve lesions associated with fractures of the humerus. J Orthop Trauma 1993;7:211–5.

6. Pollock FH, Drake D, Bovill EG, Day L, Trafton PG. Treatment of radial neuropathy associated with fractures of the humerus. J Bone Joint Surg Am 1981;63:239–43.

7. Shaw JL, Sakellarides H. Radial-nerve paralysis associated with fractures of the humerus. A review of forty-five cases. J Bone Joint Surg Am 1967;49:899–902.

8. Kettelkamp DB, Alexander H. Clinical review of radial nerve injury. J Trauma 1967;7:424–32.

9. Sonneveld GJ, Patka P, van Mourik JC, Broere G. Treatment of fractures of the shaft of the humerus accompanied by paralysis of the radial nerve.

Injury 1987;18:404–6.

10. Samardzic M, Grujicic D, Milinkovic ZB. Radial nerve lesions associated with fractures of the humeral shaft. Injury 1990;21:220–2.

11. Gosler MW, Testroote M, Morrenhof J, Janzing H. Surgical versus nonsurgical interventions for treating humeral shaft fractures in adults. Cochrane Database Syst Rev 2012:1.

12. Beaty J. Humeral shaft fractures. orthopaedic knowledge update. Rosemont Ill. Am Acad Orthop Surg 1999:278–86.

13. Huttunen TT, Kannus P, Lepola V, Pihlajamäki H, Mattila VM, Surgical

treatment of humeral-shaft fractures: a register-based study in Finland between 1987 and 2009. Injury 2012;43:1704–8.

14. Seddon H. Peripheral nerve injuries. Medical Research Council Special Report Series No. 282. London: Her Majesty’s Stationary Office 1954:1–7.

15. Walker M, Palumbo B, Badman B, Brooks J, Van Gelderen J, Mighell M. Humeral shaft fractures: a review. J Shoulder Elbow Surg 2011;20:833– 44.

16. DeFranco MJ, Lawton JN. Radial nerve injuries associated with humeral fractures. J Hand Surg Am 2006;31:655–63.

17. Shah A, Jebson PJ. Current treatment of radial nerve palsy following fracture of the humeral shaft. J Hand Surg Am 2008;33:1433–4.

18. Elton SG, Rizzo M. Management of radial nerve injury associated with humeral shaft fractures: an evidence-based approach. J Reconstr Microsurg 2008;24:569–73.

19. Ekholm R, Ponzer S, Tornkvist H, Adami J, Tidermark J. Primary radial nerve palsy in patients with acute humeral shaft fractures. J Orthop Trauma 2008;22:408–14.

20. Kim DH, Kam AC, Chandika P, Tiel RL, Kline DG. Surgical management and outcome in patients with radial nerve lesions. J Neurosurg 2001;95:573–83.

21. Lowe JB, 3rd, Sen SK, Mackinnon SE. Current approach to radial nerve paralysis. Plast Reconstr Surg 2002;110:1099–113.

22. Modabber MR, Jupiter JB. Operative management of diaphyseal fractures of the humerus. Plate versus nail. Clin Orthop Relat Res 1998:93–104.

23. Klenerman L. Fractures of the shaft of the humerus. J Bone Joint Surg Br 1966;48:105–11.

24. Packer JW, Foster RR, Garcia A, Grantham SA. The humeral fracture with radial nerve palsy: is exploration warranted? Clin Orthop Relat Res 1972;88:34–8.

25. Niver GE, Ilyas AM. Management of radial nerve palsy following fractures of the humerus. Orthop Clin North Am 2013;44:419–24.

26. Garcia A, Maeck BH. Radial nerve injuries in fractures of the shaft of the humerus. Am J Surg 1960;99:625–7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kararlı olmayan kapalı humerus cismi kırığı ile ilişkili radiyal sinir felcinin primer eksplorasyonu Dr. Soo-Hong Han, Dr. In Tae Hong, Dr. Ho Jae Lee, Dr. Sang June Lee, Dr. Uk Kim, Dr. Dong Won Kim CHA Üniversitesi Tıp Fakültesi, Ortopedik Cerrahi Anabilim Dalı, CHA Bundang Tıp Merkezi, Seong-nam-Kore Cumhuriyeti

AMAÇ: Kapalı humerus cismi kırığının neden olduğu radyal sinir felcinin tedavisi tartışmalıdır. Bu çalışmanın amacı, kararlı olmayan kapalı humerus cismi kırıkları olan hastalarda radiyal sinir felcinin erken evrede tedavisinin sonlanımını değerlendirmek ve bu tip yaralanması olan hastaların cerrahi yolla eksplore edilip edilmemesi gerektiğini belirlemektir.

GEREÇ VE YÖNTEM: Kararlı olmayan kapalı humerus cismi kırıklarının tedavisi için açık redüksiyon ve internal fiksasyon geçirmiş 15 ardışık hastanın tıbbi kayıtları gözden geçirildi. Yaralanma mekanizmaları, radyogramlar, zedelenmiş sinirin intraoperatif bulguları ve klinik iyileşmeler irdelendi. On beş hastanın ikisi basit düşme, ikisi beyzbol oynarken, biri kayak yaparken biri de iş sırasında makineye kaptırmıştı. Kırıklar 6 hastada humerusun ortasında 8 hastada orta-distalinde ve bir hastada orta-proksimalinde bulunuyordu. Kırıklar 6 hastada transvers kırık, 4 hastada kelebek fragmanlı parçalı kırık, 3 hastada oblik segmentli kırık ve 2 hastada spiral kırık şeklindeydi.

BULGULAR: On bir hastada makroskopik olarak sinirler sağlamdı ve dördünde sinir tamamen enine kesilmişti. Total sinir kesisi olan dört hasta trafik kazası geçirmişti. Bu dört hastanın birinde humerus cisminin orta-distal kısmında kelebek fragmanlı parçalı kırık, diğer üçünde ise yine humerus cisminin orta-distalinde deplase transvers kırık mevcuttu. İki olguda enine kesili sinirler primer onarıldı. Diğer iki olguda sinir uçları ezilmiş olduğu için humerus boyu kısaltıldı ve sinir grefti kondu. Sağlam sinirli hastaların tümü son izlemde tamamen fonksiyonlarına kavuşmuştu.

TARTIŞMA: Kararlı olmayan humerus cismi kırığının eşlik ettiği radiyal sinir felcinin tedavisi için tercihen radiyal sinirin primer eksplorasyonu, açık redüksiyon, kırığın plakayla tespiti düşünülmelidir. Yüksek enerjili travma, orta-distal humerusta lokalize kırık ve basit transvers kırık veya kelebek fragmanlı parçalı kırığın radiyal sinir transeksiyonu için risk faktörleri olduğu görünmektedir.

Anahtar sözcükler: Humerus kırığı; primer eksplorasyon; radiyal sinir felci.

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doi: 10.5505/tjtes.2017.26517

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ORIG I N A L A R T IC L E

Long-term results of primary repair of combined cuts on the median and ulnar nerves in the forearm Kemal Özaksar, M.D.,1 Hüseyin Günay, M.D.,2 Levent Küçük, M.D.,2 Erhan Coşkunol, M.D.2 1

Department of Orthopedics and Traumatology, EMOT Hospital, İzmir-Turkey

2

Department of Orthopedics and Traumatology, Ege University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: The objective of this clinical study was to evaluate sensory and motor functions in the later period following primary repair of combined injuries of the ulnar and median nerves in the forearm at proximal, middle, and distal levels.

METHODS: Later period sensory evaluation of ulnar and median combined cuts was performed using two-point discrimination and monofilament tests. On the other hand, motor evaluation was performed by determining dorsal palmar interosseus strength for the ulnar nerve and abductor pollicis brevis muscle strength for the median nerve. Cold intolerance, object recognition, and weight discrimination were also reviewed.

RESULTS: In total, 26 patients with ulnar-median combined cut and aged between 5 and 59 years were included in this study. Although no deficiency was observed in the sensory functions of any of the patients, a decrease in tactile sensation was detected in the median sensory region in 12 (46%) patients and in the ulnar sensory region in 7 (26%) patients. The most significant loss in terms of motor functions was detected in the opposition pinch strength. Two patients developed claw hand and two showed joint contracture.

CONCLUSION: Ideal treatment for peripheral nerve injuries should be primary repair. Restoration of the motor function in the median nerve is relatively easier than that in the ulnar nerve. No significant difference was observed in terms of sensory function. An alternative is needed for primary repair because of lack of motor function in proximal ulnar incisions. There is no standardization of tests performed for peripheral nerve repair.

Keywords: Forearm; median nerve; primary repair; ulnar nerve.

INTRODUCTION

MATERIALS AND METHODS

Nerve injuries often occur with penetrating lacerations or glass cuts on the forearm and are most commonly accompanied by tendon and/or vessel injuries. These injuries may be isolated median or ulnar nerve injuries as well as a combination of both, particularly on the volar side of forearm.

Combined nerve injuries are very important reasons of morbidity in young and active persons that may cause sensorial and motor sequel. In this study, sensory and motor functions were evaluated after primary repair of combined injuries of the ulnar and median nerves in the forearm.

Of a total of 71 patients who underwent early primary repair after being admitted to the emergency service because of ulnar-median combined nerve cuts in one extremity at the forearm level, 26 patients were included in this study. The patients in this group were aged 5–59 years and were followed up for an average of 119 (75–168) months. Twenty-five of the patients were male (96%), while only one was female (4%). Of all the patients, 20 had a cut on the right forearm, whereas six had a cut on the left forearm. Injuries were detected on the dominant arms in 24 patients and on the non-dominant arms in 2 patients.

Address for correspondence: Hüseyin Günay, M.D. Ege Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İzmir, Turkey Tel: +90 232 - 390 27 12 E-mail: drgunayh@yahoo.com.tr Submitted: 28.06.2016 Accepted: 07.02.2017

Ulus Travma Acil Cerrahi Derg 2017;23(5):410–414 doi: 10.5505/tjtes.2017.92744 Copyright 2017 TJTES

410

Patients were prepared using a pneumatic tourniquet on the arm level in the supine position. Debridement and irrigation were performed on the surface of the injury. Tendons were sutured using modified Kessler method with 3–0 or 4–0 polydioxanone suture (PDS) after exploring the vessels, nerves, and tendons on the forearm. Vessels and nerves were repaired using 8–0, 9–0, and 10–0 nylon sutures. The epiperineural suture technique was employed during nerve repairs.

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Patients were provided with a short- or long-arm dorsal splint postoperatively. All sutures were removed on the 14th day and controlled active–passive exercises were begun from the 3rd day onward. Splints were kept intact for at least 3 weeks.

Median and ulnar nerve sensory evaluations of the followup patients were performed according to British Medical Research Council’s Sensory Recovery Classification (BMRC) modified by Mackinon and Dellon.[1] A comparison was performed based on the uninjured extremity’s motor and sensory examinations. Tactile and pressure sensations were evaluated using Semmes–Weinstein monofilaments.[2] The static and dynamic two-point discrimination test was used for detecting the distance between two points sensible in the injured nerve innervation. The test was performed on the second finger pulp for the median nerve and on the fifth finger pulp for the ulnar nerve.[3] Water cups cooled down to +4°C were used for the cold intolerance evaluation.

In dynamic and static two-point discrimination test, high scores discovered in favor of the operated hands as opposed to the non-operated ones were regarded as significant (p<0.05). No result of significance was manifested in twopoint discrimination tests at the innervation sites of the median and ulnar nerves on the operated sides (p>0.05).

Patients were shown 10 different objects to perform the object recognition test, having been asked to recognize the objects blindfolded on a given duration first using their nonoperated hand and then using their operated hand.[4]

The abductor pollicis brevis muscle strength did not reveal any bad results, whereas it was shown to be average for 12 pa-

Anesthesia was not spotted in any of the patient during the monofilament test. An improvement in protective sensation was observed in all patients. Although a decrease in tactile and protective sensations was detected in 12 and 7 patients, respectively, who underwent median nerve repair, 7 patients showed normal values for tactile and protective sensations.

In the ulnar nerve, a decrease in tactile and protective sensations was observed in 7 and 11 patients, respectively, whereas 8 patients displayed normal results tactile and protective sensations (Table 3).

Table 1. Tests used for evaluation

Weight discrimination test was performed by asking patients to discriminate similar-looking objects of different weights first using the non-operated hand and then using the operated hand. A total of 10 objects were used in our study, ranging from 75 to 125 g.

Sensory evaluation

BMRC modified Mackinon-Dellon

Two-point discrimination

Cold intolerance

Median nerve, 2. fingers

Ulnar nerve, 5. finger pulp

Grip strength was observed using the Jamar hydraulic dynamometer for motor innervation evaluation. A mean score was recorded after repeating the measurement three times.

Tip, key, and palmar pinch and opposition strength were evaluated using a pinch meter.[5]

Tactile pressure

Semmes-Weinstein

Object recognition test

Weight recognition test

Motor evaluation

Jamar hydraulic dynamometer

All measurements were performed by a single hand surgeon (Table 1).

Pinch (tip, key, and palmar)

Oppositon strength

In statistical analysis of the results, paired t-test was used for metric measurements and one-way ANOVA and Kruksal–Wallis test were used for comparison between different groups. If significant differences were observed between the groups, Mann–Whitney test was performed, having performed Bonferroni correction. In addition, Spearman and Pearson correlation tests were performed.

RESULTS Fifty-two nerves from 26 patients who responded final examination call, were evaluated in terms of motor and sensory recovery. In line with BMRC criteria, 15 patients with median nerve cuts revealed good results, whereas 8 patients had perfect and 3 patients had bad results on sensory evaluation. Same evaluation showed good results in 16 patients with ulnar cuts, perfect results for 7 patients, and bad results for 3 patients (Table 2).

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Pinchmeter

Table 2. Results according to BMRC criteria

Perfect Good Bad

Ulnar 8 15 3 Median 7 16 3 BMRC: British Medical Research Council’s Sensory Recovery Classification.

Table 3. Monofilament test − number of patients with diminished sensory function

Tactile sensation

Protective sensation

Normal

Ulnar 7

11

8

Median 12

7

7

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Ă&#x2013;zaksar et al. Long-term results of primary repair of combined cuts on the median and ulnar nerves in the forearm

Table 4. Motor strength evaluation (abductor pollicis brevis muscle strength for the median nerve and dorsal interosseus muscles strength for the ulnar nerve)

Good Average Bad

Ulnar 7 11 8 Median 12

7 7

tients and good for 14 patients during motor evaluation of the median nerve. The dorsal palmar interosseus muscle strength was evaluated for the ulnar nerve. Results were bad in 13 patients, average in 11 patients, and good in 2 patients (Table 4).

Grip strength results were 32.27 kg for operated hands and 40.41 kg for non-operated hands. The average loss of strength for grip was 20.2%. Considering a durable hand at 100% strength, the highest loss of strength was observed in the opposition pinch (57.33%).

In an evaluation that divides patientsâ&#x20AC;&#x2122; forearms in three equal

parts, 10 injuries were observed at the distal, 11 at the median, and 5 at the proximal levels. During motor strength evaluation, while recovery was observed to be fine in median nerve injuries at the distal level, the same recovery rate was detected to be average for the ulnar nerve. An evaluation of the median and proximal regions showed average recovery for the median nerve and bad recovery for the ulnar nerve. Although no significant difference was spotted for sensory recoveries, the average results were observed as good (Fig. 1).

Cold intolerance was found to be disturbing for 3 patients and mediocre for 12 patients and no intolerance was detected in 11 patients. A negative correlation was observed between cold intolerance, sensory recovery of the median nerve, and object recognition test (p<0.05).

Another negative correlation was observed between age, object recognition, and weight discrimination tests. A positive correlation was observed between object recognition and sensory and motor recoveries in the median nerve (p<0.01).

Figure 1. Postoperative 75th month.

Figure 2. Postoperative 156th month.

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Table 5. Difficulties in daily activities Daily activity Number of cases with complication

Buttoning

Taking money out of wallet

Opening jars

Cold intolerance

15

11

9

14

Although two patients showed claw hand development on physical examination, one patient had proximal interphalangeal joint contracture in his second finger by 20° and another in his fourth finger by 30°. Opposition loss was detected in 11 patients (Fig. 2).

In terms of daily activities, 15, 11, and 9 patients had difficulty in buttoning, taking money out of a wallet, and opening jars, respectively. Three out 5 patients with proximal injury and 9 out of 11 patients with mediocre injury were reported to return their jobs prior to the incident. Four patients were reported to change profession (Table 5).

DISCUSSION Upper extremity nerve injuries are often the result of glass cuts or injuries by perforating objects. These are mostly accompanied by vessel or tendon injuries. Physiological outcomes that follow nerve injuries and their repair depend on the proximity of the injury to the nerve cell, quality of axonal growth, adaptation of regenerated axons, distance of the end motor organ to the injury zone, and vitality. Ideal treatment for peripheral nerve injuries because the neurotransmitter secretion will continue, is primary repair with best results can be obtained.[6] All of our patients underwent early primary repair.

In literature, large series are encountered where long-term results of ulnar nerve combined cuts were evaluated.[4,7] Combined cuts are particularly mentioned in journals alongside isolated cuts, and it is reported that repair results badly influence motor functions. In their compilation of 130 journals, Ruijs et al. reported that of a total of 638 cases of forearm nerve cuts, 138 cases (21.6%) were of combined cuts.[7] Kılınç et a. reported that of their 40 case series, 13 were combined injuries and that sensory functions were protected better in isolated ulnar cuts than in isolated median cuts, but that no difference was present in motor functions, adding that most cases of combined cuts needed a secondary surgery (92%).[8] Although differences were found to be significant when the injured and non-injured sides were compared, no difference was observed between the median and ulnar on the operated side.

Brich did not come across bad results in 108 median and ulnar nerve cuts with primary repairs.[9] In our study, too, no bad results were encountered in terms of sensory abilities, and it was thought that a sensory flaw would regain function in time.

Age being an important factor in sensory defect recovery was reported on a better emphasized platform on cuts to which a primary repair was performed during the adolescent period.[10] A loss in motor function was observed, although the recovered muscle strength in the median innervation region was Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

better than that in the ulnar innervation region. Although the recovery of median nerve was found to be sufficient in 14 patients, only 2 patients with ulnar nerve cuts showed a sufficient motor recovery. As the level of the lesion extended proximally, poor motor recovery of the ulnar nerve was detected. Better function was obtained in intrinsic muscles by transferring the terminal branch of the anterior interosseus nerve to the ulnar motor branch in ulnar nerve lesions present on higher levels or combined median ulnar cuts.[11,12] Moberg was the first who studied the relationship between two-point discrimination and functional tests. It was reported that recovery of dynamic two-point discrimination and functional tests, as they are related to rapidly adapting fibers, could be influenced by the rehabilitation program and that because the conveyance of static two-point discrimination is concerned with fibers that adapt slowly, it will reflect the surgical outcome better.[13] On sensory evaluation of median cuts at the wrist level, Polatkan et al. detected no correlation between monofilament test and two-point discrimination.[14] In our study, significant correlation was detected between these two tests in both median and ulnar autonomous regions.

The object recognition test has an ostensible sensibility rate in terms of displaying changes over time. No standardization exists between the test materials. Because the region on which the test can be performed includes only the first three fingers in the radial region, it can only be used in median nerve cuts.

Although a significant correlation was detected between object recognition and median nerve recovery in our study, the same correlation was not seen in ulnar nerve recovery. This test displayed a negative correlation with age and a positive correlation with weight discrimination (p<0.01).

Claw hand deformity, discorded finger movements, and loss of lateral hand movements of fingers as well as diminishing grasp and grip strength are among the basic restrains peculiar to ulnar nerve lesions. Noamann in his own series reported that following combined cuts, 6.5% patients showed a major deformity,13.5% patients showed a minor deformity, and 80% showed no signs of deformity.[15] Hudson reported observing 7 claw deformities throughout the 49 months of follow-up in his 15 combined cut series.[16] Only two patients developed claw hand deformity in our series including 26 patients.

The epiperineural suture technique was used on our patients using a microscope or loop magnification. Experimental and clinical studies have not indicated the superiority of fascicular repairs over epineural repairs. A discussion still persists on 413

Özaksar et al. Long-term results of primary repair of combined cuts on the median and ulnar nerves in the forearm

this subject.[17–19] The general impression focuses on obtaining nerve integrity using simple suture techniques.

Conclusion In combined cuts, sensory recovery is in an acceptable level in lesions of all levels. No significant difference was detected between median and ulnar nerves in terms of sensory recovery. Motor function recovery was observed to be better in the median nerve than in the ulnar nerve. Insufficient motor recovery causes important limitations in patient’s daily activities and work lives.

Conflict of interest: None declared.

REFERENCES 1. Mackinnon SE, Dellon AL. Surgery of the peripheral nerve. New York: Thieme Medical Publishers; 1988.

2. Bell-Krotoski JA, Fess EE, Figarola JH, Hiltz D. Threshold detection and Semmes-Weinstein monofilaments. J Hand Ther 1995;8:155–62.

3. Dellon AL, Mackinnon SE, Croby PM. Reiability of two point discrimination measurements. J Hand Surg 1987;12:693.

4. Bruyns CN, Jaquet JB, Schreuders TA, Kalmijn S, Kuypers PD, Hovius SE. Predictors for return to work in patients with median and ulnar nerve injuries. J Hand Surg Am 2003;28:28–34.

5. Mathiowetz V, Weber K, Volland G, Kashman N. Reliability and validity of grip and pinch strength evaluations. J Hand Surg Am 1984;9:222–6.

6. Trehan SK, Model Z, Lee SK. Nerve Repair and Nerve Grafting. Hand Clin 2016;32:119–25.

7. Ruijs AC, Jaquet JB, Kalmijn S, Giele H, Hovius SE. Median and ulnar nerve injuries: a meta-analysis of predictors of motor and sensory recovery after modern microsurgical nerve repair. Plast Reconstr Surg 2005;116:484–94.

8. Kilinc A, Ben Slama S, Dubert T, Dinh A, Osman N, Valenti P. Results

of primary repair of injuries to the median and ulnar nerves at the wrist Chir Main 2009;28:87–92.

9. Birch R, Raji AR. Repair of median and ulnar nerves. Primary suture is best. J Bone Joint Surg Br 1991;73:154–7.

10. Rosén B, Lundborg G. The long term recovery curve in adults after median or ulnar nerve repair: a reference interval. J Hand Surg Br 2001;26:196–200.

11. Haase SC, Chung KC. Anterior interosseous nerve transfer to the motor branch of the ulnar nerve for high ulnar nerve injuries. Ann Plast Surg 2002;49:285–90.

12. Phillips BZ, Franco MJ, Yee A, Tung TH, Mackinnon SE, Fox IK. Direct radial to ulnar nerve transfer to restore intrinsic muscle function in combined proximal median and ulnar nerve injury: case report and surgical technique. J Hand Surg Am 2014;39:1358–62.

13. Chassard M, Pham E, Comtet JJ. Two-point discrimination tests versus functional sensory recovery in both median and ulnar nerve complete transections. J Hand Surg Br 1993;18:790–6.

14. Polatkan S, Orhun E, Polatkan O, Nuzumlali E, Bayri O. Evaluation of the improvement of sensibility after primary median nerve repair at the wrist. Microsurgery 1998;18:192–6.

15. Noaman HH. Management and functional outcomes of combined injuries of flexor tendons, nerves, and vessels at the wrist. Microsurgery 2007;27:536–43.

16. Hudson DA, De Jager LT. The spaghetti wrist. Simultaneous laceration of the median and ulnar nerves with flexor tendons at the wrist. J Hand Surg Br 1993;18:171–3.

17. Mafi P, Hindocha S, Dhital M, Saleh M. Advances of peripheral nerve repair techniques to improve hand function: a systematic review of literature. Open Orthop J 2012;6:60–8.

18. Marsh D, Barton N. Does the use of the operating microscope improve the results of peripheral nerve suture? J Bone Joint Surg Br 1987;69:625– 30.

19. Nakatsuchi Y, Matsui T, Handa Y. Funicular orientation by electrical stimulation and internal neurolysis in peripheral nerve suture. Hand 1980;12:65–74.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ön kol seviyesinde median ulnar sinir kombine kesilerinin primer tamirinin uzun dönem sonuçları Dr. Kemal Özaksar,1 Dr. Hüseyin Günay,2 Dr. Levent Küçük,2 Dr. Erhan Coşkunol2 1 2

EMOT Hastanesi, Ortopedi ve Travmatoloji Kliniği, İzmir Ege Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İzmir

AMAÇ: Bu klinik çalışmada amaç ön kolda proksimal, orta ve distal seviyelerde ulnar ve median sinirin birlikte kesilerinin erken primer tamiri sonrası geç dönemde duyu ve motor fonksiyonlarının değerlendirilmesidir.

GEREÇ VE YÖNTEM: Ulnar ve median kombine kesilerde geç dönem duyu değerlendirilmesi iki nokta ayrım testi, monoflaman testi ile yapıldı.

Motor değerlendirme ise ulnar sinir için dorsal palmar interosseöz gücü, median sinir için abduktor pollisis brevis kas gücü değerlendirildi. Soğuk intoleransı, obje tanıma ve ağırlık ayırt etme de değerlendirildi.

BULGULAR: Çalışmaya ulnar median kombine kesisi olan 5–59 yaş arası 26 hasta dahil edildi. Hastaların hiç birinde duyu fonksiyonlarında yetersizlik gözlenmezken median duyusal alanda 12 (%46) hastada, ulnar duyusal alanda yedi (%26) hastada dokunma duyusunda azalma saptandı. Motor fonksiyon açısından en anlamlı kayıp oppozisyon pinch gücünde saptandı. İki hastada pençeleşme, iki hastada eklem kontraktürü gözlendi.

TARTIŞMA: Periferik sinir yaralanmalarında ideal tedavi primer tamir olmalıdır. Motor fonksiyon dönüşü median sinirde ulnara göre daha iyidir.

Duyusal açıdan anlamlı fark yoktur. Distal seviyede median ve ulnar sinirin grup yapısı oluşturması nedeniyle epiperinöral tamir yerine grup fasiküler tamir tercih edilmelidir. Proksimal ulnar kesilerde motor fonksiyon yetersizliği nedeniyle primer tamire alternatif gerekmektedir. Periferik sinir tamiri için yapılan testlerde standartizasyon yoktur.

Anahtar sözcükler: Median sinir; önkol; primer tamir; ulnar sinir.

Ulus Travma Acil Cerrahi Derg 2017;23(5):410–414

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doi: 10.5505/tjtes.2017.92744

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ORIG I N A L A R T IC L E

ESIN and K-wire fixation have similar results in pediatric both-bone diaphyseal forearm fractures Namık Şahin, M.D.,1 Yavuz Akalın, M.D.,2 Oğuz Türker, M.D.,2 Güven Özkaya, M.D.3 1

Department of Orthopaedics and Traumatology, Medical Sciences University, Konya Training and Research Hospital, Konya-Turkey

2

Department of Orthopaedics and Traumatology, Medical Sciences University, Bursa Yüksek İhtisas Health Application and

Research Center, Bursa-Turkey 3

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

ABSTRACT BACKGROUND: The purpose of this study was to compare short-term radiographic and clinical results of pediatric both-bone diaphyseal forearm fractures treated with intramedullary nail fixation using titanium nails or K-wires.

METHODS: This was a prospective comparative trial. In total, 43 patients with both-bone open or closed forearm fractures who underwent surgical treatment with intramedullary fixation were randomly classified into two groups. Three patients did not return for the follow-up and were excluded from the study. Twenty of the 40 patients were assigned to the elastic stable intramedullary nail group and 20 were assigned to the K-wire group. Demographic data suggested no difference between the two groups except for the side of injury. Perioperative data and radiological and clinical outcomes were evaluated.

RESULTS: The cohort comprised 5 girls and 35 boys whose mean age was 11.60 ± 2.69 years. Except the proportion of patients who were conservatively followed up preoperatively, all perioperative data were similar between the groups. Radiographic and functional results were similar. There were two delayed unions; one pin track infection and one re-fracture.

CONCLUSION: Intramedullary fixation of forearm fractures in children with titanium nail or K-wire does not affect radiological and clinical results. Both elastic stable intramedullary nail and K-wire fixation were effective in stabilizing pediatric diaphyseal forearm fractures.

Keywords: Forearm; fracture; intramedullary nail; pediatrics.

INTRODUCTION Forearm fractures are generally considered to be the most common injuries in children. Closed reduction and cast application are the gold standard treatment for minimally displaced and stable forearm fractures in the pediatric group.[1–3] Most patients aged <8 years will remodel even bayonet apposition and angular deformity of at least 10°–15°, but particularly in children older than 12 years of age, unstable diaphyseal fractures of the forearm treated conservatively remodel poorly Address for correspondence: Namık Şahin, M.D. Sağlık Bilimleri Üniversitesi, Konya Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Konya, Turkey Tel: +90 332 - 221 00 00 E-mail: sahinnamik@yahoo.com Submitted: 08.07.2016 Accepted: 12.01.2017

Ulus Travma Acil Cerrahi Derg 2017;23(5):415–420 doi: 10.5505/tjtes.2017.85891 Copyright 2017 TJTES

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

and may result in malunion.[2,4] Malunion of the forearm could cause loss of motion, particularly in pronation and supination and lead to unsatisfactory functional outcomes.[5,6] Therefore, particularly in children with irreducible and unstable forearm fractures, the rate of those who chose surgical treatment for pediatric forearm fractures has increased in the last decade.

[7,8] A nationwide study conducted in Finland showed that the annual incidence of operatively treated forearm fractures increased by 62% between 1997 and 2006.[7] Accepted surgical indications for pediatric both-bone diaphyseal forearm fractures include irreducible, unstable, highenergy, or open fractures.[9] Intramedullary (IM) fixation is currently the commonly preferred technique for diaphyseal forearm fracture treatment in children.[9,10] The other approved and preferred procedures are plate and screw fixation, a combination of plate-screw and IM fixation, and single bone osteosynthesis.[11–13] Although there are some studies, the type of implant to be preferred for IM nailing is not well studied. The aim of this study was to compare functional and radiographic outcomes of elastic stable IM nailing (ESIN) and 415

Şahin et al. ESIN and K-wire fixation have similar results in pediatric both-bone diaphyseal forearm fractures

K-wire fixation for treating both-bone diaphyseal forearm fractures in children.

MATERIALS AND METHODS This was a prospective, randomized, and comparative trial.

Between April 2014 and May 2015, 43 patients with bothbone open or closed forearm fracture who underwent surgical treatment with IM fixation were randomly allocated into two groups. Three patients did not return for the follow-up and were excluded from the study. Twenty of the remaining 40 patients were assigned to the ESIN group (ESIN fixation for both the radius and ulna) and 20 were assigned to the K-wire group (K-wire fixation for both the radius and ulna).

The inclusion criteria were (1) patients aged 8–16 years, (2) both-bone forearm fractures be included in 22-D4 and 22-D5 according to the AO Pediatric Comprehensive Classification of Long Bone Fractures,[14] (3) failure to obtain or maintain adequate closed reduction[15] (>10° angulation in the AP or lateral plane, any rotation of both bones, and translation of bone fragments > half of the bone diameter), (4) no previous forearm injuries, (5) no pathologic fractures, and (6) no Gustilo–Anderson type 3B or 3C open fractures.[16] Informed consent was obtained from all parents and from all children aged ≥12 years. Approval for this investigation was obtained from the local ethical committee.

Demographic data suggested no difference between the two groups except for the side of injury (Table 1). Perioperative

data included duration from injury to surgery, duration of surgery, type of reduction (open or closed), duration of immobilization postoperatively, and duration from primary surgery to implant removal.

Surgical Technique All patients were operated under general anesthesia. The standard operative technique as described by Lascombes et al.[17] was used in all cases. Closed reduction was first tried under fluoroscopy. After closed or open reduction, the radial fracture was fixed retrograde using a titanium elastic nail in the ESIN group and using a K-wire in the K-wire group and advanced through a drill hole just proximal to the distal radial epiphysis. The ulnar fracture was fixed IM with a lateral approach through the posterolateral part of the olecranon.

Titanium nails have pre-bent tips. The tip of the K-wires was bent by the surgeon with an angulation of 20°–30°. All titanium nails and K-wires curved to approximately 20° at the fracture level. Implants were chosen with a diameter of 2 mm for those aged ≤10 years and with a diameter of 2.5 mm for those older. A 3.2-mm drill size was chosen for all children (Figs. 1 and 2).

Both groups followed the same postoperative procedure, which was above elbow cast immobilization until callus formation was observed on plain radiographs or maximum at 6 weeks. Sutures were removed 14 days postoperatively. All patients returned for evaluation after postoperative 1st, 2nd,

Table 1. Patients demographics and fracture characteristics

ESIN Group (n=20)

K-wire Group (n=20)

p

Age1 (years)

12.05 (±2.52)

11.15 (±2.83)

0.324

Height1 (cm)

139.8 (±11.88)

135.25 (±14.11)

0.277

Weight1 (kg)

40.9 (±8.66)

36.5 (±9.13)

0.126

Sex2 0.342

Boy

19 (95%)

16 (80%)

Girl

1 (5%)

4 (20%)

Side od injury 0.011 2

Right

14 (70%)

6 (30%)

Left

6 (30%)

14 (70%)

Mechanism of injury2 0.407

Simple fall

15 (75%)

18 (90%)

High-energy trauma

5 (25%)

2 (10%)

Fracture classification

0.490

2

22D4

13 (65%)

15 (75%)

22D5

7 (35%)

5 (25%)

Conservative treatment history2 0.022

No

16 (80%)

9 (45%)

Yes

4 (20%)

11 (55%)

Data are presented as (mean±SD). 2Data are presented as frequency (%). SD: Standard deviation.

1

416

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Şahin et al. ESIN and K-wire fixation have similar results in pediatric both-bone diaphyseal forearm fractures

3rd, 4th and 6th weeks, and 3rd, 6th and 12th months, respectively.

Wrist and elbow mobility exercises were initiated 3–4 weeks postoperatively.

(a)

(b)

Radiologic evaluation was performed in the 3rd and 6th weeks and in the 3rd, 6th, and 12th months. Fracture union was defined by bridging callous across at least three cortices of the bone on anteroposterior and lateral radiographic views based on the description by Schmittenbecher et al.,[18] which defined fracture union beyond 3 months as “delayed union” and that beyond 6 months as “nonunion.”

(c)

(d)

(e)

(f)

Functional outcomes were evaluated at the end of the postoperative 1st year according to the criteria developed by Price et al.[2] The pronation and supination ranges of the fractured forearm were measured using a conventional goniometer.[5] The outcomes were graded as follows: excellent, if no complaints with strenuous physical activity or a loss of pronationsupination of <10°; good, if mild complaints with strenuous activity and/or 11°–30° loss of forearm rotation; fair, if subjective complaints during daily activities and/or 31°–90° loss of forearm rotation; and all other results were considered to be poor. The loss of forearm motion on the affected side was compared with that on the unaffected forearm.

Complications were classified as “minor” (recover with observation or minimal intervention) and “major” (requiring a return to the operating room or resulting in significant longterm sequelae).

Statistics All statistical analyses were performed using IBM SPSS ver.

23.0. The Shapiro–Wilk test was used to test normality.

Continuous variables were compared using Mann–Whitney U test and t-test. Categorical variables were compared using Pearson’s chi-squared test, Fisher’s exact test, and FisherFreeman-Halton test. A p-value of <0.05 was considered to be significant.

RESULTS The cohort comprised 5 girls and 35 boys. The mean age was 11.60±2.69 years. The mean height was 137.5±13.08 cm and the mean weight was 38.7±9.06 kg. Except the proportion of patients who were conservatively followed preoperatively, all perioperative data were similar between the groups (Table 2).

Furthermore, both radiographic and functional results were similar (Table 3).

There were three open fractures in total. Two of them were Gustilo–Anderson type 2 open fractures in the ESIN group and one was type 1 in the K-wire group (p>0.05). There were two patients with delayed union, and they had open fractures (each in both groups). One child in the ESIN group developed pin-tract infection in the radius because of skin irritation. This Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Figure 1. (a) Anteroposterior and (b) lateral radiographs showing displaced and angulated diaphyseal both-bone right forearm fractures in an 8-year-old girl. (c) Early anteroposterior and (d) lateral radiographs showing IM K-wire fixation of ulna and radial fractures in the same patient. (e) Anteroposterior and (f) lateral radiographs of the forearm after hardware removal.

(a)

(b)

(c)

(d)

(e)

(f)

Figure 2. (a) Anteroposterior and (b) lateral radiographs showing displaced and angulated diaphyseal both-bone right forearm fractures in a 13-year-old boy. (c) Early anteroposterior and (d) lateral radiographs showing IM titanium nail fixation of ulna and radial fractures in the same patient. (e) Anteroposterior and (f) lateral radiographs of the forearm after hardware removal.

was successfully treated with oral antibiotics and wound care.

In the K-wire group, one patient had a re-fracture 4 months postoperatively following the removal of the pins. This was also successfully treated with open reduction and IM fixation.

DISCUSSION The main finding of our study was that IM fixation of forearm fractures with ESIN or K-wire in children does not affect radiological and clinical results. There was no significant difference in the union time of fractures, rate of postoperative complications, range of motion of the elbow and wrist, and postoperative symptoms. When all patients were evaluated together, IM fixation of forearm fractures in children has successful results and lower complication rate than those reported in other studies.[1,10,19] Although closed reduction and cast immobilization remains the gold standard treatment for minimally displaced and 417

Şahin et al. ESIN and K-wire fixation have similar results in pediatric both-bone diaphyseal forearm fractures

Table 2. Perioperative data

ESIN Group (n=20)

Duration from injury to surgery (days)1 Duration of surgery (min)1

K-wire Group (n=20)

p

4 (1–15)

6.5 (1–22)

0.405

43.5 (30–65)

45 (30–65)

0.283

Type of reduction (Radius) 0.527 2

Closed

11 (55%)

9 (45%)

Open

9 (45%)

11 (55%)

Type of reduction (Ulna)2

Closed

15 (75%)

15 (75%)

Open

5 (25%)

5 (25%)

1.000

16 (10–52)

16 (10–26)

0.753

4 (3–6)

4 (3–6)

0.839

Implant removal time (weeks) 1

Duration of immobilization postoperatively (weeks)1

Data are presented as median (min-max). Data are presented as frequency (%).

1

2

Table 3. Radiologic and clinical results

Delayed union2 Union time (weeks) 1

ESIN Group (n=20)

K-wire Group (n=20)

p

1 (5%)

1 (5%)

1.000

6.5 (5–24)

6 (5–13)

0.383

Clinical result2 0.695

Excellent

14 (70%)

17 (85%)

Good

5 (25%)

2 (10%)

Fair

1 (5%)

1 (5%)

Poor

–

–

Data are presented as median (min-max). 2Data are presented as frequency (%).

1

stable pediatric forearm fractures,[1,2] the rate of operative treatment of pediatric forearm fractures has substantially increased in the last decade.[7,8] However, the optimal method for surgical fixation of pediatric forearm fractures is still controversial. Well-established surgical options include IM nailing,[1,10,20] open reduction and internal fixation with plates and screws, and hybrid fixation.[10,12,21] In a systematic review, Patel et al.[10] reported similar functional and radiographic outcomes and complications with IM nails and plates used in the treatment of both-bone diaphyseal forearm fractures in children. But they stated that IM nailing was an effective treatment option for these fractures with shorter operating times, improved cosmesis, and easier hardware removal. In another study, Feng et al.[12] compared clinical outcomes of hybrid fixation using ESIN for radius and plate-screw fixation for the ulna with dual ESIN fixation for both-bone forearm fractures in children. They reported that hybrid fixation has some advantages in terms of the times of fluoroscopy during surgery, duration of immobilization postoperatively, delayed union of the ulna, and the average time of bone union.

418

Although IM nailing is well-accepted and generally preferred technique for diaphyseal forearm fracture treatment in young children, the type of implant was not well-established. Several advantages of ESIN fixation have been described for pediatric both-bone forearm fractures.[10,22] Antabak et al.[22] reported that ESIN osteosynthesis for diaphyseal forearm fractures remains a valid technique with good functional results. However, some complications of ESIN, including delayed union and nonunion of the ulna, infection and skin irritation, implant migration or failure, loss of reduction, nerve and tendon injury, and compartment syndrome, have been reported.[1,12,22] Yung et al.[23] also concluded that percutaneous IM K-wiring with immobilization in a cast is an easy, minimally invasive, and safe method with a good functional outcome. He stated that only 5 of 57 patients had angulation from 10° to 15° and none had nonunion, premature epiphyseal closure, or deep infection.

Calder et al.[24] assessed the outcome of K-wires or ESIN as the method for fracture stabilization in such diaphyseal forearm fractures and demonstrated no difference in outcome between K-wires and ESIN as our study, although the nails do offer some theoretical advantages.

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Despite theoretical advantages of ESIN fixation, like more elastic properties of titanium nails than K-wires achieving better three-point fixation and stabilization,[17] it is unclear whether this property provides some clinical advantages in both-bone forearm fractures. In this study, both K-wires and titanium nails were less bent than in the original technique, regardless of whether they provided three-point fixation or not. But because of this modification, all patients underwent plaster immobilization to ensure rotational stability. The advantages of three-point fixation may be rotational stability in addition to providing radioulnar spacing, and some patients do not need plaster immobilization. On the other hand, there are known cost implications between the two kind of implants. K-wires are less expensive at 12 TL per wire compared with 322 TL per nails for titanium nails. This price difference could be important, particularly in developing countries.

Removal of implants remains a controversial issue. Removing plates is usually harder than removing nails. When removing metalwork, the risk of re-fracture must be considered. In some studies, nails were routinely removed in all patients[19,25] and in others, none or some were removed.[1] Furthermore, re-fractures were reported in both ESIN and plating groups.

Implant removal times were also variable. Although early removal of implants may result in re-fractures, delayed removal may reveal surgical difficulties. We removed all implants postoperatively at a relatively early period and re-fracture occurred in only one patient.

Although the children were blinded for the implant, the orthopedic surgeon was not blinded during clinical follow-up, which might have influenced clinical measurements. Obviously, blinding of the surgeon was impossible because of radiologic evidence of the implant type. Postoperative immobilization was used in all patients in both groups. But this study did not evaluate whether all of the patients needed immobilization or not. In this study, we treated patients aged between 8 and 16 years with IM fixation. However, particularly in older adolescents, there may possibly be a threshold in terms of age, which would make plate and screw fixation more effective. This could be determined in a future study.

Conclusion In conclusion, in our study, fewer complications were observed in pediatric both-bone forearm fractures with IM nailing compared with the results of other studies. Both ESIN and K-wire fixation were effective in stabilizing pediatric diaphyseal forearm fractures. There was no significant difference between the two techniques in terms of union time of fractures, rate of postoperative complications, range of motion of the elbow, and postoperative symptoms.

Conflict of interest: None declared.

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15. Colaris JW, Allema JH, Reijman M, de Vries MR, Ulas Biter L, Bloem RM, et al. Which factors affect limitation of pronation/supination after forearm fractures in children? A prospective multicentre study. Injury 2014;45:696–700.

16. Gustilo RB, Simpson L, Nixon R, Ruiz A, Indeck W. Analysis of 511 open fractures. Clin Orthop Relat Res 1969;66:148–54.

17. Lascombes P, Haumont T, Journeau P. Use and abuse of flexible intramedullary nailing in children and adolescents. J Pediatr Orthop 2006;26:827–34.

18. Schmittenbecher PP, Fitze G, Godeke J, Kraus R, Schneidmuller D. Delayed healing of forearm shaft fractures in children after intramedullary nailing. J Pediatr Orthop 2008;28:303–6.

19. Fernandez FF, Egenolf M, Carsten C, Holz F, Schneider S, Wentzensen A. Unstable diaphyseal fractures of both bones of the forearm in children: plate fixation versus intramedullary nailing. Injury 2005;36:1210–6.

20. Luhmann SJ, Gordon JE, Schoenecker PL. Intramedullary fixation of

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21. Wyrsch B, Mencio GA, Green NE. Open reduction and internal fixation of pediatric forearm fractures. J Pediatr Orthop 1996;16:644–50.

22. Antabak A, Luetic T, Ivo S, Karlo R, Cavar S, Bogovic M, et al. Treatment outcomes of both-bone diaphyseal paediatric forearm fractures.

Injury 2013;44 Suppl 3:11–5.

23. Yung SH, Lam CY, Choi KY, Ng KW, Maffulli N, Cheng JC. Percuta-

neous intramedullary Kirschner wiring for displaced diaphyseal forearm fractures in children. J Bone Joint Surg Br 1998;80:91–4.

24. Calder PR, Achan P, Barry M. Diaphyseal forearm fractures in children treated with intramedullary fixation: outcome of K-wire versus elastic stable intramedullary nail. Injury 2003;34:278–82.

25. Teoh KH, Chee YH, Shortt N, Wilkinson G, Porter DE. An age- and sex-matched comparative study on both-bone diaphyseal paediatric forearm fracture. J Child Orthop 2009;3:367–73.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Çocuk önkol çift kırıklarında ESIN ve K-teli tespiti benzer sonuçlara sahiptir Dr. Namık Şahin,1 Dr. Yavuz Akalın,2 Dr. Oğuz Türker,2 Dr. Güven Özkaya3 Sağlık Bilimleri Üniversitesi, Konya Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Konya Sağlık Bilimleri Üniversitesi, Bursa Yüksek İhtisas Sağlık Uygulama ve Araştırma Merkezi, Ortopedi Ve Travmatoloji Anabilim Dalı, Bursa 3 Uludağ Üniversitesi Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Bursa 1 2

AMAÇ: Bu çalışmanın amacı titanium çivi ya da K-telleri kullanılarak intramedüller çivileme ile tedavi edilen çocuk önkol kırıklarının kısa dönem radyolojik ve klinik sonuçlarının karşılaştırılmasıdır.

GEREÇ VE YÖNTEM: Bu çalışma ileriye yönelik karşılaştırmalıdır. İntramedüller tespit ile cerrahi olarak tedavi edilen açık ya da kapalı önkol çift kırıklı 43 hasta randomize olarak iki gruba ayrıldı. Takibi yapılamayan üç hasta çalışmadan çıkarıldı. Kırk hastadan 20’si elastik stabil intramedüller çivi grubuna ve 20’si de K-teli grubuna dahil edildi. Demografik veriler yaralanmanın tarafı dışında iki grup arasında benzerdi. Perioperatif veriler, radyolojik ve klinik sonuçlar değerlendirildi.

BULGULAR: Kohort yaş ortalaması 11.60 (±2.69) olan 5 kız ve 35 erkek çocuktan oluşuyordu. Ameliyattan önce konservatif olarak takip eilen hastaların oranı dışında tüm perioperatif veriler gruplar arasında benzerdi. Radyolojik ve klinik sonuçlar da benzer idi. Toplamda iki kaynama gecikmesi, bir tel dibi enfeksiyonu ve bir refraktür gözlendi.

TARTIŞMA: Çocuklarda önkol kırıklarının titanyum çivi ya da K-teli ile intramedüller tespitinin radyolojik ve klinik sonuçları benzerdir. Hem elastik stabil intramedüller çivi hem de K-teli tespiti pediatrik diafizeal önkol kırıklarının tedavisinde etkindir.

Anahtar sözcükler: Çocuk; intramedüller çivi; kırık; önkol.

Ulus Travma Acil Cerrahi Derg 2017;23(5):415–420

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doi: 10.5505/tjtes.2017.85891

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CAS E SERI ES

Diaphragmatic rupture: A single-institution experience and literature review Carlo Corbellini, M.D., Stefano Costa, M.D., Tiberio Canini, M.D., Roberta Villa, M.D., Ettore Contessini Avesani, M.D. Department of General Surgery and Emergency Surgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan-Italy

ABSTRACT BACKGROUND: Diaphragmatic rupture (DR) is a rare and potentially life-threatening event caused by trauma or spontaneously.

DR occasionally occurs several months after the injury. Chest X-ray and computed tomography are the most effective diagnostic methods. Delay in DR diagnosis occurs frequently. This study aimed to examine and improve our understanding of the etiology, clinical presentation, and management of DR. METHODS: This study was performed at the Emergency and General Surgery Department of Fondazione I.R.R.C.S. Cà Granda, Ospedale Policlinico in Milan (Italy). Patients diagnosed with DR between 2001 and 2011 who underwent surgery were included, and their data were retrospectively collected.

RESULTS: Fourteen patients were diagnosed with DR, mainly left-sided DR. Road traffic collisions were the main causes (86%). DR diagnosis was preoperatively established in eight patients (57%). Chest X-ray was diagnostic in 50% of the patients and computed tomography in three patients (60%). Twelve patients had a diaphragmatic hernia. DR was repaired with a mesh in two patients. Mean hospital stay was 16.6 days.

CONCLUSION: Difficulty in achieving early diagnosis of DR is due to its nonspecific presentation. High index of suspicion is needed.

Its treatment is using surgery involving reduction of the viscera and repair of the diaphragm defect.

Keywords: Diaphragmatic hernia; diaphragmatic rupture; spontaneous diaphragmatic rupture; traumatic diaphragmatic rupture.

INTRODUCTION Diaphragmatic rupture (DR) is a rare pathological event that is commonly caused by trauma, as that in road traffic accidents (RTAs) or penetrating injuries.[1–3] DR diagnosis can be immediate or delayed after the main trauma. A different cause of DR is represented by spontaneous DR (SDR). Diaphragmatic hernia (DH) occurs when one or more abdominal structures protrude through the diaphragm.

Address for correspondence: Carlo Corbellini, M.D. Department of General Surgery and Emergency Surgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico 20122, Via Francesco Sforza, 36 - Milan, Italy Tel: +39-02-55033298 E-mail: carlo.corbellini@yahoo.it Submitted: 01.03.2016 Accepted: 24.01.2017

Ulus Travma Acil Cerrahi Derg 2017;23(5):421–426 doi: 10.5505/tjtes.2017.78027 Copyright 2017 TJTES

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Symptoms can vary depending on the DR phase and the clinical setting, and thus, the diagnosis can be easily missed. Surgical treatment is usually required to reduce herniated organs and repair the defect.

MATERIALS AND METHODS In this study, we evaluated all patients with DR (ICD-9 Codes: 862.XX, 552.3 and 553.3) who were admitted to the Emergency and General Surgery Department (ESD) of Fondazione I.R.C.C.S. Cà Granda, Ospedale Maggiore Policlinico, in Milan (Italy) between January 2001 and December 2011. Each patient who was diagnosed with DR with or without a history of high-energy trauma and had undergone a surgery was included. Patients with a history of hiatal hernia or congenital DH were excluded. We could not determine whether the patients admitted at our ESD were misdiagnosed with DR. DR diagnosis was attested using imaging studies or during the surgical procedure. Data were extracted retrospectively and double-checked by two authors (C.C. and R.V.). Patient data regarding age, sex, mechanism of injury, associated injuries, symptoms, diagnostic imaging methods, time to diagnosis 421

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(time from hospital admission to correct diagnosis), size of rupture, presence of hernia, surgical treatment, postoperative complications and mortality, were evaluated.

RESULTS

Table 2. Associated injuries Body region Injury description

No. of patients

Head

Closed head injury

3

Fourteen patients (nine males and five females) with a mean age of 37 (range, 19â&#x20AC;&#x201C;79) years were included. Detailed data on patient characteristics, injury details, diagnosis timing, and clinical outcomes are reported in Table 1. RTA was the most common category of trauma (11 intervehicular and one pedestrian), whereas one patient had penetrating trauma. A case of spontaneous DR during a gymnastic exercise was reported in our case series. Hemorrhagic shock occurred in six of 10 patients with acute traumatic injury at admission (60%). The main symptom was dyspnea, and others common symptoms were nausea, chest pain, cough, and epigastric pain. Multiple associated injuries were detected in 10 patients (Table 2), and rib fracture was the most common injury (70%).

Facial injury

4

Chest

Pulmonary contusion

3

Rib fracture

7

Sternum fracture

1

The diaphragm defect was left-sided in 12 patients (86%) and right-sided in two (14%); no bilateral DR was found. Herniation of the abdominal organs into thorax was detected in 12 patients (intraoperatively in nine and preoperatively in three).

Detailed data on the herniated organs are presented in Table 3.

DR was preoperatively diagnosed in eight of 14 patients (57%) and during surgery in six (43%). The interval between traumatic event and DR diagnosis ranged from 1 h to 96 months.

Intraoperative diagnosis was achieved in five of 10 patients

Pneumothorax

2

Hemothorax

4

2

Vertebral process fracture

Abdomen Liver

1

Bowel

1

Renal

1

Spleen with hemoperitoneum

3

Spleen without hemoperitoneum

1

Orthopedics

Upper extremities

1

Lower extremities

1

Vertebral

2

1

Spinal cord

Pelvis

4

with acute blunt DR (BDR) (50%). In four of five patients with acute BDR, the preoperative diagnosis was established in less than 12 h after arrival at our ESD. Three patients without an

Table 1. Characteristics of patients, injury details, timing diagnosis, and clinical outcomes No Gender

1

Age Cause of injury (years)

Haemorrhagic shock (Yes/No)

Associated injuries (Yes/No)

Time to diagnosis*

Postoperative complication

Male

31

Road traffic accident

Yes

Yes

i.o.

No

2

Male

31

Stab wound (11 months before)

No

No

<12 h

No

3

Female

53

Road traffic accident

No

Yes

>12 h

Yes

4

Female

79

Road traffic accident (pedastrian)

Yes

Yes

<12 h

No

5

Male

33

Road traffic accident

No

No

<12 h

No

No

Yes

i.o.

Yes

(46 months before)

6

Male

24

Road traffic accident

7

Male

19

Road traffic accident

Yes

Yes

i.o.

i.o. death

8

Male

43

Road traffic accident

No

Yes

<12 h

No

9

Male

28

Road traffic accident

No

No

<12 h

No

(96 months before)

10

Female

21

Road traffic accident

Yes

Yes

i.o.

No

11

Female

27

Road traffic accident

Yes

Yes

<12 h

No

12

Male

43

Road traffic accident

No

Yes

<12 h

No

13

Female

41

Gymnastiic exercise

No

No

i.o.

No

14

Male

50

Road traffic accident

Yes

Yes

i.o.

Yes

i.o.: Intra operative diagnosis; After arrival at the ESD. *

422

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(a)

Table 3. Diaphragmatic injury and herniated organs Variable

(b)

No. of patients

Location Right

2

Left

12

Size

<6 cm

3

Between 6 and 10 cm

8

>10 cm

3

Herniated organs

Stomach

7

Bowel

5

Liver

2

Spleen

2

Omentum

2

None

2

Figure 1. (a) A negative chest radiograph of a patient presenting with BDR (Case 12). (b) A diagnostic posteroanterior chest radiograph of a patient with a delayed DR that had occurred during gymnastic exercise. Immediate decompression with a nasogastric tube was required. An elevated left hemidiaphragm can be observed (Case 13).

acute injury presented a medical history of previous trauma: one with stab wound 11 months previously, one with RTA 46 months previously, and another with RTA 96 months previously. These patients presented delayed DR, and dyspnea was the common symptom. Diagnosis was established in these patients in less than 12 h after arrival at the ESD. The only patient with SDR was preoperatively diagnosed.

The diagnostic methods included chest X-ray, computed tomography (CT), ultrasonography (USG), and oral contrast studies. We obtained chest radiographs from 10 patients, and radiographs of five of them (50%) were reported as normal.

The chest radiographs usually showed nonspecific signs as diaphragm elevation with loss of right costo-diaphragm angle (Figure 1a and 1b). Five hemodynamically stable patients underwent thoracoabdominal CT, in three of whom (60%), CT scan was diagnostic. In these three patients, chest radiograph findings were consistent with diagnosis on CT scan. Abdominal USG was performed in five patients, which provided specific information concerning DR in two patients (40%). Two patients underwent a positive X-ray oral contrast study (Figure 2).

All 14 patients underwent surgery. Laparotomy (eight emergency laparotomies) was performed in nine patients and thoracotomy in four. One patient underwent left thoracoabdominal approach. The median size of acute BDR (large diameter) and DR was 8±2.7 cm and 5±4 cm, respectively. The size of rupture in the patient with SDR was 6 cm. The herniated organs were always reduced into the abdomen. The diaphragm defect was repaired with non-absorbable direct suture in 12 patients. In two patients, a polypropylene prosthetic mesh was placed following the primary repair of DR. Splenectomy was performed in five patients: in four of whom, the spleen was herniated in the thorax, and in one, bleeding from an iatrogenic spleen occurred in the absence of herniation. A transverse colon resection with colostomy was performed because of bowel perforation.

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Figure 2. A gastrografin follow-through revealed an elevation and a discontinuity of left hemidiaphragm with herniated stomach into the left hemithorax (Case 13).

A polytraumatized patient died at the end of surgery for cardiocirculatory arrest following hemorrhagic shock. The mean hospital stay was 16.6 (range, 5–53) days. Three patients (27%) had postoperative pulmonary-related complications, which were successfully treated conservatively. In the other eight patients, recovery was uneventful.

DISCUSSION Any event that can lead to a sudden increase in intra-abdominal pressure may result in DR.[4] In 1974, Grimes described three phases for DR. The acute phase denotes the onset of clinical symptoms at the time of injury. Development to the second phase may take months or even years. The delayed phase is explained by two hypotheses: delayed rupture or delayed detection. Missed diagnosis during the early period of trauma may lead to progressive herniation of intra-abdominal contents into the thorax, and occasionally, visceral obstruction or strangulation occurs.[5–7] 423

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The incidence of diaphragmatic injuries in patients with blunt abdominal trauma is estimated to be 0.8%–5%.[8] RTAs are the most common cause of BDR.[5] In our study, 12 patients (86%) had a recent (10 patients) or previous (two patients) RTA. BDRs are usually observed in the left diaphragm (68.6%–87%) [9] because this area has a weak pleuroperitoneal membrane structure; in contrast, right-side DRs are encountered only in 5%–19% of all DR cases.[10,11] Bilateral hemiDR is rare.

DH is an unusual condition; it occurs in 1%–7% of patients with DR following major blunt trauma and in 10%–15% of patients with penetrating trauma and DR.[3] Our case series describes 12 DHs: three DHs with delayed presentation, one DH due to SDR, and eight DHs detected after acute traumatic injury. The organs most commonly involved in leftsided DH are the stomach and colon (Table 3). In our study, DH was a common event because the study mainly involved polytraumatized patients. The displacement of abdominal organs was more common in delayed hernias, which is consistent with the results in literature. Bowel obstruction, without any evidence of ischemia, was observed in two patients, both with delayed presentation of DH. SDR is an extremely rare condition accounting for less than 1% of cases of DR.[9] SDR is defined as a damage of the diaphragm due to an increased pressure in the chest or abdominal cavity without direct trauma. In our case series, a single case of SDR was observed and it was associated with DH. Symptoms in patients with DR may vary depending on the DR phase.[12] In blunt or penetrating trauma, DR is usually associated with reduced breath sounds, orthopnea, and dyspnea.[10,13–15] In the study by Popovic et al.,[16] the main presenting symptoms were epigastric pain, nausea, vomiting, and meteorism.[11] These evidences demonstrated that the diagnosis can be easily missed. In the literature, a great variability in diagnosis timing has been reported.[8,11] The rate of initially missed diaphragmatic injuries range from 12% to 66% after an acute trauma.[17,18] Many investigation techniques have been described for DR diagnosis, but no diagnostic method has a higher sensitivity or specificity than other methods; nonetheless, CT can be considered as the gold standard in an emergency setting in stable patients.[13,19] In our study, the two most commonly used techniques were chest X-ray and CT. In the literature, consistent with our results, it has been reported that only 25%–50% of the initial chest radiographs are diagnostic for BDR.[18,20] Furthermore, sensitivity of CT in diagnosing acute DR ranges between 33% and 83%, and its specificity ranges between 76% and 100%.[18,21] CT findings in acute DR are hemidiaphragmatic discontinuity, intrathoracic herniation of the abdominal content, and the dependent viscera sign.[22,23] In our series, CT revealed a DR in three of five stable polytraumatized patients. A chest X-ray was performed in these three patients, and the findings were consistent with diagnosis on CT. USG may allow the visualization of large DR or DH, but this imaging method is rarely used for 424

first-time investigation. Magnetic resonance imaging can be a good diagnostic tool, but it cannot be performed in an emergency setting.[21] Oral follow-through study was performed in two patients, and it revealed positive results; chest X-ray results in both these patients were negative. The patients with SDR demonstrated negative results on chest X-ray, chest CT, upper gastrointestinal endoscopy, and abdominal USG before being diagnosed using oral follow-through. In our patients with delayed DR, the diagnostic approaches were varied: two patients underwent X-ray barium enema because of bowel obstruction presentation, and in one patient, CT scan was diagnostic for right-sided DH associated with liver and colon herniation. As frequently observed, the preoperative diagnostic rate of DR was lower in polytraumatized patients than in others. This was because of the high complexity in these patients and their difficult management. On exposed evidence, we believe that CT with oral water-soluble contrast can be useful in patients in whom DR is highly suspected.

Surgical management is mandatory and requires the reduction of herniated content, repair of the defect, and occasionally, drainage of the pleura. This surgical management can be achieved by thoracic or abdominal approach.[24] Our most common surgical approach was laparotomy (four median and six subcostal) because of the type of trauma and hemodynamic instability of the patients. Surgical procedure included thoracotomy only in four patients and laparotomy was added for one patient to reduce herniated contents. Thoracotomy was the preferred approach described by Schummer[25] and Kotoulas.[26] Igai[27] chose posterolateral thoracotomy plus right subcostal laparotomy.

Thoracoscopy, laparoscopy, or both approaches combined have been described in the literature as useful methods to diagnose and treat DR, even in acute trauma.[28,29] Some authors have reported that endoscopic freeing is often difficult in chronic DH (CDH) because of the strong adhesions between the herniated viscera and pleura.[30] However, several authors have reported good results of the laparoscopic repair of CDH.[8,31–35] Liao et al have reported rapid recovery and decreased postoperative hospital stay after applying the pledgeted suture method in CDH treatment that involves compressing and approximating the edges of the diaphragm together and releasing the shearing force when applying ties.[36] In our opinion, considering the addition of a thoracotomy in an unmanageable patient, laparotomy represents the best choice of treatment in cases of complex thoracic and abdominal acute trauma because it allows the widest abdominal view to search for any other injuries. In our case series, thoracotomy alone was performed in two patients with delayed DR and in one patient with acute DR. This last patient had exhibited hemodynamic stability at arrival and the presence of a negative abdominal CT scan.

Primary repair is the gold standard for small- or moderateUlus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

Corbellini et al. Diaphragmatic rupture

size diaphragmatic defects, whereas large defects (larger than 10 cm) may require patch closure with a mesh. In emergency surgery, patch closure is not usually recommended. Polytetrafluoroethylene, polyethylene terephthalate, and polypropylene are the most common materials used in prosthetic patches to repair DR; some cases with patch infection followed by hernia recurrence have been reported in the literature.[37] We believe that primary repair with non-absorbable sutures is the best technique for diaphragm repair and that prosthetic mesh should be placed when a lack of substance is detected, as usually occurs in delayed presentation of DR. Pulmonary complications are reported to be the most common postoperative occurrence.[38] Our experience supports this evidence. Associated organ injuries, hemorrhagic shock, missing or delayed diagnosis, rather than the DR itself, result in increased morbidity and mortality.[5,39] Other authors have reported no worsening of prognosis with delayed diagnosis followed by surgical repair.[19] In the literature, mortality rates in patients with acute diaphragm injury differ from those in patients with delayed DH.[3,5,38] In our case series, delayed diagnosis and age were not factors affecting patient outcomes.

Furthermore, the low mortality rate recorded (one patient) did not reveal a significant association between reported associated injuries and outcomes.

In conclusion, we can affirm that DR remains a diagnostic challenge because of nonspecific symptoms and signs and low sensitivity of imaging methods. DR repair is mandatory, and prosthetic mesh should be placed when a large DR is detected. It is not possible to define the best management considering the low incidence of DR, the acute setting, and variety of presentation, and diagnostic and treatment options. It is fundamental to maintain high clinical suspicion index in highrisk and compromised trauma patients.

Conflict of interest: None declared.

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World J Surg 2012;36:260–5.

38. Sözüer EM, Ok E, Avşaroğullari L, Küçük C, Kerek M. Traumatic diaphragmatic ruptures. Ulus Travma Derg 2001;7:176–80.

39. Hanna WC, Ferri LE, Fata P, Razek T, Mulder DS. The current status of traumatic diaphragmatic injury: lessons learned from 105 patients over 13 years. Ann Thorac Surg 2008;85:1044–8.

OLGU SERİSİ - ÖZET

Diyafragma rüptürü: Tek bir kurum deneyimi ve literatürün gözden geçirilmesi Dr. Carlo Corbellini, Dr. Stefano Costa, Dr. Tiberio Canini, Dr. Roberta Villa, Dr. Ettore Contessini Avesani IRCCS Cà Granda Vakfı, Maggiore Hastanesi Polikliniği, Genel Cerrahi ve Acil Cerrahi Kliniği, Milan-İtalya

AMAÇ: Diyafragma rüptürü (DR) seyrek görülen, travma sonucu veya kendiliğinden oluşan yaşamı tehdit edici potansiyeli olan bir olaydır. Bazen DR yaralanmadan birkaç ay sonra oluşur. Göğüs filmi ve bilgisayarlı tomografi en etkili tanısal yöntemlerdir. Sıklıkla DR tanısı gecikir. Bu çalışmanın amacı DR etiyoloji, klinik tablosu ve tedavisini incelemek ve daha iyi anlamaktır.

GEREÇ VE YÖNTEM: Bu çalışma İtalya, Milano I.R.R.C.S. Vakfı Cà Granda Hastanesi Acil ve Genel Cerrahi Bölümü Polikliniği’nde [Emergency and General Surgery Department of Fondazione I.R.R.C.S. Cà Granda, Ospedale Policlinico in Milan (Italy)] gerçekleştirildi. 2001 ila 2011 yılları arasında DR tanısı konup ameliyat geçirmiş hastalar çalışmaya dahil edilip geriye dönük olarak hastaların verileri toplandı.

BULGULAR: Çoğu sağ tarafta DR olan 14 hastaya tanı konmuştur. Başlıca neden trafik kazalarıydı (%86). Sekiz hastada (%57) ameliyat öncesi DR tanısı konmuştu. Göğüs filmi hastaların %50’sine tanı koydurmuş, üç olguda (%60) bilgisayarlı tomografi yararlı olmuştur. On iki hastada diyafragma hernisi mevcuttu. İki olguda DR meş ile onarılmıştır. Ortalama hastanede kalış süresi 16.6 gün idi.

TARTIŞMA: Nonspesifik kliniği nedeniyle erken tanı koymada zorluk yaşanmaktadır. Çok kuşkucu olmak gerekir, tedavisi cerrahidir. İç organlar içeri itilir ve diyafragma defekti onarılır.

Anahtar sözcükler: Diyafragma hernisi; diyafragma rüptürü; spontan diyafragma rüptürü; travmatik diyafragma rüptürü.

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CAS E R EP O RT

Klingsor syndrome: A rare surgical emergency Gaurav Aggarwal, M.D., Samiran D Adhikary, M.D. Department of Urology, Apollo Hospital, Bhubaneshwar, Odisha-India

ABSTRACT Klingsor syndrome or self-Inflicted traumatic penile amputation is a rare clinical entity that is associated with psychiatric disorders, command hallucinations, religious preoccupations, substance abuse, and isolation from or neglect by society. In addition to being infrequently encountered, it is a rare surgical emergency, with paucity of data on appropriate and timely management to ensure optimal functional outcomes. We report the case of a 25-year-old unmarried male who inflicted this injury upon himself in a fit of paranoia as a way to expiate his sins and earn solace from God. An attempt at microvascular re-implantation 12 h after the injury was successful, with adequate cosmetic and functional outcomes obtained.Thus, in this rare disease, despite a delay in presentation, a single attempt at re-implantation may still be worthwhile for obtaining optimal cosmetic and psychosocial benefits.

Keywords: Klingsor syndrome; penile self-amputation; urological emergency.

INTRODUCTION Klingsor syndrome or self-Inflicted traumatic penile amputation is a rare clinical entity; it is usually associated with psychiatric disorders, command hallucinations, religious preoccupations, substance abuse, and isolation from or neglect by society.[1,2] It is infrequently encountered and is a rare urological emergency; there is paucity of data on this syndrome in terms of adequate and timely management.

We report the case of a 25-year-old unmarried male who inflicted this injury upon himself as a way to expiate his sins and earn solace from God. An attempt at microvascular reimplantation 12 hours after the injury was successful with adequate cosmetic and functional outcomes obtained.

CASE REPORT A 25-year-old unmarried male with no past medical or psychiatric history was brought to the emergency department in a hemodynamically stable condition and with a self-inflicted Address for correspondence: Gaurav Aggarwal, M.D. Department of Urology, Apollo Hospital Bhubaneshwar, India Tel: +91-7873947779 E-mail: drgaurav1981@rediffmail.com Submitted: 26.05.2016 Accepted: 16.01.2017

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penile injury; the amputated distal penile appendage was in a clean dry bag. He had self-mutilated himself around 12 h ago at the behest of “inner commanding voices” that had “reassured” him of complete solace and expiation of his sins.

Despite the long duration, post trauma, the appendage appeared viable; therefore, with adequate consent, an attempt at re-implantation was planned.

The patient was immediately taken to the operation theatre (Figure 1). The patient was injected with amoxicillin/clavulanic acid under general anesthesia; microvascular re-implantation of the penile appendage was performed (using prolene 8-0 and 9–0 interrupted sutures; under 2.5× magnification), ensuring adequate debridement of nonviable tissues. The immediate postoperative appearance was cosmetically acceptable (Figure 2).

The postoperative course of the patient was uneventful, with evaluation and initiation of psychiatric treatment (with a diagnosis of paranoid schizophrenia) and oral ketoconazole for 10 days postoperatively to prevent immediate penile engorgement. He was discharged on the eight postoperative day without any event. At the 2-month follow up, he was asymptomatic and his cosmetic and functional outcomes were adequate.

DISCUSSION Self-inflicted penile amputation is an extremely uncommon injury, with literature reports stating that approximately 87% 427

Aggarwal et al. Klingsor syndrome

Both microscopic as well as non-microscopic techniques have provided equivocal results in various reports, considering the fact that repair of a single dorsal penile artery may be more important than repairing multiple profunda arteries.[7] Although re-implantation is the gold standard, it may always not be possible to achieve the same on account of significant local ischemia and prolonged duration post trauma.[5] In our case, despite the long duration, a single attempt at re-implantation was made, with consent received from the patient’s relatives after they were explained about the guarded prognosis. Circumcision should be avoided as the preputial skin may be an important appendage for use in future reconstructions, if necessary.

Figure 1. Preoperative appearance, after local tissue debridement.

In instances of delay at presentation, other options include closure of the distal stump or phallic replacement and reconstruction after the acute injury has healed.[5] The adequate length of the phallus to be kept for adequate postoperative functioning is debatable and depends on the level of penile injury as well as the surgical expertise.[5] Postoperative complications include local skin loss, which is common, and penile necrosis and urethrocutaneous fistulae, which are rare.[8]

Figure 2. Immediate postoperative appearance.

of patients suffer from undiagnosed psychiatric disorders and around 51% of these have “decompensated schizophrenia”.

[1,2] Some patients may be socially isolated due to severe bipolar depression or due to them having religious delusions.[3] Various risk factors implicated in reports worldwide include elderly single males, trans-sexual or homosexual tendencies, or as a guilty feeling for self-committed sexual offences.[2–4] Irrespective of the underlying etiology, Klingsor syndrome is an important urological emergency, mandating early and prompt treatment, to achieve optimal prognosis. Being infrequently seen, there are no set management protocols.

In 1929, Ehrlich was the first to document a case of macroscopic penile re-implantation; in 1977, Cohen et al. reported on the first microvascular re-implantation.[4] It has been postulated that as microsurgical techniques minimize the skin, urethra, and graft loss as well as enable better vascular and nerve repair, they may be more beneficial in preserving the sensation of the organ, micturition, and erectile function.[5–7] The use of non-microsurgical techniques has also been reported with varying degrees of success, and a review by Volkmer et al.[6] even questioned the value of these microsurgical techniques.[7]

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Nevertheless, microvascular re-implantation remains the treatment of choice with the highest probability of adequate cosmetic as well as functional outcomes.[5,8] A concomitant psychiatric evaluation is mandatory to ensure optimal functional outcomes and prevent such occurrences in the future. In our case a diagnosis of “paranoid schizophrenia” was made, and the patient was promptly initiated on medications for the same. Such patients need long-term follow-up to ensure effective psychosocial rehabilitation in addition to support from the society and family in particular.

Conclusion Self-inflicted penile amputation is a rare urological emergency that mandates immediate and timely surgical intervention to ensure optimal cosmetic and functional outcomes. The ideal management algorithm however depends on a multidisciplinary approach involving a urologist as well as a psychiatrist.

Till such time, we have to rely on isolated case reports to ensure awareness on this entity.

A single attempt at re-implantation, without circumcision, despite a slightly prolonged delay at presentation, may be worthwhile, taking into account future cosmesis and functionality.

Conflict of interest: None declared.

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REFERENCES 1. Bhargava SC, Sethi S, Vohra AK. Klingsor Syndrome: A Case Report.

Indian J Psychiatry 2001;43:349–50.

2. Kochakarn W. Traumatic amputation of the penis. Braz J Urol 2000;26:385–9.

3. Ozan E, Deveci E, Oral M, Yazici E, Kirpinar I. Male genital self-mutilation as a psychotic solution. Isr J Psychiatry Relat Sci 2010;47:297–303.

4. Bhatt YC, Vyas KA, Srivastava RK, Panse NS. Microneurovascular reimplantation in a case of total penile amputation. Indian J Plast Surg

2008;41:206–10.

5. Wei FC, McKee NH, Huerta FJ, Robinette MA. Microsurgical replantation of a completely amputated penis. Ann Plast Surg 1983;10:317–21.

6. Volkmer BG, Maier S. Successful penile replantation following autoamputation: twice! Int J Impot Res 2002;14:197–8.

7. El Harrech Y, Abaka N, Ghoundale O, Touiti D. Genital self-amputation or the Klingsor syndrome: Successful non-microsurgical penile replantation. Urol Ann 2013;5:305–8.

8. Kochakarn W, Muangman V, Krauwit A. Traumatic penile amputation: results with primary reattachment. J Urol 1997;157:857.

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Klingsor sendromu: Seyrek görülen cerrahi acil Dr. Gaurav Aggarwal, Dr. Samiran D Adhikary Apollo Hastanesi, Üroloji Kliniği, Bhubaneshwar, Odisha, Hindistan

“Klingsor sendromu” veya “kişinin kendi penisini ampüte etmesi” seyrek görülen bir klinik durum olup psikiyatrik bozukluklar, emir alma varsanısı, dinsel saplantılar, madde kötüye kullanımı, toplumdan izole edilme veya ihmal edilme ile ilişkilidir. Nadiren rastlandığı gibi seyrek görülen bir cerrahi acildir. Optimal sonuçları güvence altına alma amacıyla uygun ve zamanında tedavi açısından yetersiz veri mevcuttur. Yirmi beş yaşında bekâr, günahlarının kefaretini ödeme ve Tanrının affını kazanma yöntemi olarak penisini yaralamıştır. Yaralanmadan 12 saat sonra gerçekleştirilen mikrovasküler reimplantasyon çabası yeterli kozmetik ve fonksiyonel sonuçlarıyla başarılı olmuştur. Bu seyrek görülen hastalıkta gecikmeye rağmen optimal kozmetik ve psikososyal yararlar için tek bir reimplantasyon denemesi bile zahmete değer.

Anahtar sözcükler: Klingsor sendromu; penis; penisini ampüte etme; ürolojik acil.

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CA S E REP OR T

Traumatic duodenal injury in children: A report of two cases Deepa Makhija, M.Ch., Shalika Jayaswal, M.Ch., Vikrant Kumbhar, M.Ch., Hemanshi Shah, M.Ch. Department of Paediatric Surgery, TNMC & BYL Nair Hospital, Mumbai, Maharashtra-India

ABSTRACT Duodenal injury following blunt abdominal trauma in children is extremely rare. It commonly has a delayed presentation, thus leading to increased mortality and morbidity. We report two cases of isolated duodenal injury following blunt abdominal trauma in children.

Keywords: Children; duodenal transection; trauma.

INTRODUCTION The duodenum is injured mostly due to crushing or shearing forces on the abdomen. The incidence of duodenal injuries due to blunt trauma is 1% to 4%.[1] Duodenal injury comprises 0.2–3.7% of all trauma-related laparotomies.[2] On an average, one to four other abdominal organ injuries are associated with duodenal trauma, which makes an isolated injury rare.[2] The anatomical location of the duodenum makes the diagnosis of an isolated duodenal injury a difficult task. Due to its rarity and subtle clinical features, its diagnosis and management is often delayed.

We report two cases of isolated duodenal injury following blunt abdominal trauma.

CASE REPORT Case 1– A two-year-old male was referred with abdominal pain and vomiting since the past three days. There was history of a fall while playing three days previously. He had tachycardia. There was no evidence of any injury externally.

His abdomen was distended, tender, and guarded. An X-ray revealed free gas under the diaphragm. On performing lapaAddress for correspondence: Hemanshi Shah, M.Ch. A L Nair Road, Mumbai Central, Mumbai, Maharashtra India, 40008 Mumbai, India Tel: 022-23027671 E-mail: hemanshisshah@gmail.com Submitted: 05.04.2016 Accepted: 10.11.2016

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rotomy, there was complete transection of the fourth part of the duodenum (Fig. 1), with severe peritoneal contamination.

Primary anastomosis with gastrojejunostomy was performed.

The patient had an uneventful recovery.

Case 2– An eleven-year-old male was referred with pneumoperitoneum seen on computed tomography performed elsewhere. He had sustained direct trauma to the upper abdominal region due to the handle bar of his bicycle. He had tachycardia. There was no evidence of any injury externally.

The upper abdomen was guarded and rigid. On performing exploratory laparotomy, there was a tear at the junction of the third and fourth part of the duodenum, involving twothirds of the circumference of the bowel (Fig. 2). Primary suturing along with gastrojejunostomy was performed. The patient had an uneventful recovery.

DISCUSSION Trauma of the duodenum is not common due to its deep, central, and retroperitoneal location.[3] It is the fourth most commonly injured intra-abdominal organ.[4] Differentiation between duodenal injuries is essential, given that duodenal hematoma and perforation require different treatments.

Suspicion could be raised depending on the mechanisms of injury. In general, duodenal hematomas result from compression of the duodenum against the vertebral column, whereas perforations potentially develop from shearing forces or simultaneous closure of the pylorus and the fourth portion of the duodenum, resulting in increased intraluminal pressure and a “blowout.” The common mechanism of seatbelt compression with hyperflexion and distraction during deceleration in a motor vehicle crash compresses the fixed duodenum against the lumbar spine, leading to a high rate of injury.[5] Our patients had a history of fall while playing and an injury due the handle bar of a bicycle.

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Makhija et al. Traumatic duodenal injury in children

or suggest subtle findings such as small amounts of unexplained fluid or unusual bowel morphology due to paraduodenal hematoma.[2] On performing computed tomography, our first patient showed free gas under the diaphragm and second patient showed pneumoperitoneum.

Figure 1. Intraoperative image showing complete transection of the duodenum.

Figure 2. Intraoperative image showing tear in the duodenum involving two-thirds of the circumference.

Abdominal pain is the most common symptom. At the time of injury, patients with duodenal injury usually experience sharp mid-epigastric pain, which is followed by signs of chemical peritonitis within the next few hours.[1] The severity of signs and symptoms can vary considerably. The mechanism of injury (acceleration and deceleration impact) along with upper abdominal tenderness and tachycardia should raise a high index of suspicion. Both our patients had tachycardia with a guarded and rigid abdomen.

Plain radiographs of the abdomen are useful when free gas is present in the retroperitoneum adjacent to the right psoas muscle around the right kidney or anterior to the upper lumbar spine. Contrast-enhanced computed tomography of the abdomen with oral and intravenous contrast media is highly sensitive for detecting small amounts of retroperitoneal air, paraduodenal hematoma, or extravasated contrast from the duodenum. Occasionally, contrast-enhanced computed tomography may reveal negative findings when performed early Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

The treatment of duodenal injuries depends on the level of damage and grade of injury. Caution must be taken to exclude other associated injuries because in 20% of the cases, duodenal injuries are associated with damage to the pancreas.

[3] Patients with duodenal hematoma can be conservatively managed (89% to 94% of cases), and duodenal hematoma resolves with nasogastric decompression and parenteral nutrition. Approximately 72% to 80% of duodenal lacerations and higher grade injuries can be repaired with primary suture, and 20–28% require a complex procedure.[3] The most common surgical technique in the treatment of duodenal lacerations is primary suturing. Another alternative is primary suture of the defect with pyloric exclusion and gastroenterostomy.

This technique is applied in case of serious duodenal injuries or delayed diagnosis. In case of complete duodenal transection, primary suture can be performed if there is little tissue loss; in cases when the ampulla of Vater is not involved and if the damage can be closed without tension. Duodenopancreatectomy is the only option in cases when duodenal injury is associated with uncontrollable bleeding from the pancreas or when duodenal injury is combined with damage of the distal part to the common hepatic duct or pancreatic duct.[3] Both our patients had duodenal transection and were managed with primary anastomosis and gastrojejunostomy.

The complication rate after duodenal injuries can be up to 20%, and an operative delay of more than 24 h has been reported to increase the complication rate to 43%. The mortality rate in patients with duodenal injuries is reportedly between 8.3% and 19%. The mortality rate directly related to duodenal injury is generally lower and is the result of duodenal dehiscence, uncontrolled sepsis, and multiple organ dysfunction syndrome.[3] Both our patients had an uncomplicated postoperative course and were asymptomatic in the follow-up.

Conclusion The diagnosis of isolated duodenal injury can be difficult owing to its rare occurrence, its anatomical location, and the absence of specific signs and symptoms. A high degree of suspicion must be maintained for diagnosing the injury early.

Primary anastomosis is generally sufficient and may require additional procedures that are tailored according to individual requirements.

Conflict of interest: None declared.

REFERENCES 1. Zelić M, Kunisek L, Petrosić N, Mendrila D, Depolo A, Uravić M. Dou-

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Makhija et al. Traumatic duodenal injury in children ble transection of complete duodenal circumference after blunt abdominal trauma without other intra-abdominal injuries. Wien Klin Wochenschr 2010;122:54–6.

2. Bhattacharjee HK, Misra MC, Kumar S, Bansal VK. Duodenal perforation following blunt abdominal trauma. J Emerg Trauma Shock 2011;4:514–7.

3. Torba M, Gjata A, Buci S, Troci A, Subashi K. Delayed presentation of

blunt duodenal injuries in children. Case report and review of literature.

G Chir 2013;34:122–4.

4. Desai K, Dorward I, Minkes R, Dillon P. Blunt Duodenal Injuries in Children. J Trauma 2003;54:640–6.

5. Santschi M, Echavé V, Laflamme S, McFadden N, Cyr C. Seat-belt injuries in children involved in motor vehicle crashes. Can J Surg 2005;48:373–6.

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Çocuklarda travmatik duodenal transeksiyon: İki olgu sunumu Dr. Deepa Makhija, Dr. Shalika Jayaswal, Dr. Vikrant Kumbhar, Dr. Hemanshi Shah TNMC ve BYL Nair Hastanesi, Pediatrik Cerrahi Kliniği, Mumbai, Maharashtra, Hindistan

Çocuklarda künt abdominal travma sonrası duodenal yaralanma son derece seyrek görülmektedir. Genellikle geç dönemde ortaya çıkar ve mortalite ve morbiditenin artmasına yol açar. Künt abdominal travma sonrası çocuklarda oluşan iki izole duodenal yaralanma olgusunu bildiriyoruz.

Anahtar sözcükler: Çocuklar; duodenal transeksiyon; travma.

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CAS E R EP O RT

Emergency endovascular treatment of a ruptured external carotid artery pseudoaneurysm caused by a cervical stab wound: A case report and literature review Junya Tsurukiri, M.D.,1 Eitaro Okumura, M.D.,1 Hiroshi Yamanaka, M.D.,1 Hiroyuki Jimbo, M.D.,2 Akira Hoshiai, M.D.1 1

Department of Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center, Tokyo-Japan

2

Department of Neurosurgery, Tokyo Medical University Hachioji Medical Center, Tokyo-Japan

ABSTRACT The formation of external carotid artery (ECA) pseudoaneurysms caused by stab wounds is a rare vascular anomaly. Although the surgical exploration of the ECA segment is the standard treatment, endovascular treatment (EVT) can be considered if there is difficulty in identifying the source of bleeding in the injured regions that are difficult to operatively access. Here we treated a young patient who had hemorrhagic instability with hemorrhage-induced coagulopathy caused by a zone III cervical stab wound with a pseudoaneurysm from the main trunk of the ECA; the patient underwent EVT and successful hemostasis. A literature review based on the data available on PubMed was conducted, and 15 published reports of 82 penetrating ECA injuries treated by EVT were identified. We concluded that EVT appears to be an effective surgical alternative for patients with hemorrhage-induced coagulopathy caused by a ruptured ECA pseudoaneurysm after a cervical stab wound.

Keywords: Bleeding; injury; interventional radiology; penetrating; shock.

INTRODUCTION Pseudoaneurysms occur as a result of total or partial disruption of the arterial wall, with the formation of a hematoma and organization. Trauma can cause disruption of the vessel wall, with extravasation of blood and formation of a hematoma and pseudocapsule that can expand because of blood pressure.[1] Carotid artery (CA) injuries occur more commonly due to blunt trauma, and CA pseudoaneurysms are often the result of blunt trauma in zone II of the neck.[2,3] Penetrating CA injuries have been reported to account for only 3% of arterial injuries.[4] Although the internal CA is more commonly injured during trauma, there are few reports on ECA injuries that have lower incidences.[5] External CA (ECA) injuries caused Address for correspondence: Junya Tsurukiri, M.D. 1163 Tatemachi Hachioji Tokyo - Japan Tel: +81 - 4256655611 E-mail: junya99@tokyo-med.ac.jp Submitted: 20.08.2016 Accepted: 09.02.2017

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by cervical stab wounds sometimes become life threatening, and the formation of ECA pseudoaneurysms caused by stab wounds is a rare vascular anomaly.[1] There are insufficient data regarding endovascular treatment (EVT) of penetrating ECA pseudoaneurysms.

We report the case of a young patient with hemorrhagic instability caused by cervical stab wounds and who underwent EVT for a ruptured ECA pseudoaneurysm.

CASE REPORT A 25-year-old man was admitted to our emergency department with hemorrhagic shock after a cervical stab wound.

His past medical history included developmental disability. His physical examination revealed a Glasgow Coma Scale score of 7 (eye = 2, verbal = 1, and motor = 4), blood pressure of 63/20 mmHg, and heart rate of 91 beats/min. Bleeding from two areas of a 6-cm stab wound at zone III of his left neck was continuous. The patient was hemodynamically unstable and immediately received initial trauma resuscitation. The hemoglobin level, hematocrit, prothrombin time/international normalized ratio, and lactate level were 6.8 g/dL [reference range (RR), 13.5–17.5 g/dL], 19% (RR, 39%–52%), 1.66, and 433

Tsurukiri et al. Endovascular treatment of a ruptured ECA pseudoaneurysm by a cervical stab wound

carefully injected because bleeding was continuous (Fig. 1c).

EVT was successful, and the pseudoaneurysm was undetectable thereafter (Fig. 1d). A total of 1600 mL of red blood cells and 800 mL of fresh frozen plasma was administered within 24 h. Three days later, none of the images revealed dilatation or disruption of the ECA wall (Fig. 1e, f). The patient was discharged from the hospital 14 days after admission without any complications (Fig. 1g).

6.2 mmol/L (RR, 2.0–5.0 mmol/L), respectively. After the rapid administration of Ringer’s lactate solution and blood transfusion, his blood pressure improved. Contrast-enhanced computed tomography (CECT) of the neck revealed remarkable bleeding and demonstrated contrast medium extravasation and a pseudoaneurysm arising from the left ECA (Fig. 1a). After CECT, his blood pressure fell to 86/36 mmHg. We believed that it would be difficult to secure and maintain a visual field during surgery for the patient in this condition; therefore, we decided to perform EVT for achieving hemostasis.

DISCUSSION

EVT was performed under general anesthesia. Angiography revealed pseudoaneurysm formation with contrast medium extravasation from the left ECA distal to the origin of the facial artery (Fig. 1b). The distal trunk of the ECA was collaterally supplied by branches of the ascending pharyngeal artery. A microcatheter (Headway, Termo, Tokyo, Japan) was selectively placed into the center of the pseudoaneurysm; this was followed by coil embolization using 4 mm × 6 cm, 3.5 mm × 8 cm, and 3.5 mm × 8 cm microcoils (ED Coil Complex, Kaneka Medics Corporation, Osaka, Japan) deployed in the pseudoaneurysm. Furthermore, 0.6 mL of Nbutyl cyanoacrylate (NBCA) (Histoacryl; Braun, Melsungen, Germany), which was mixed with iodized oil (Lipiodol; Andre Guerbet, Aulnay-sous-Bois, France) at a ratio of 1:1, was

In a search of the literature using Medline, 15 published reports of 82 penetrating ECA injuries that underwent EVT were identified (Table 1).[1,6–19] Twenty-four patients had pseudoaneurysms at the ECA, and gunshots were the main cause of pseudoaneurysm formation in the ECA. The ECA and its branches are protected from external force by soft tissues until the artery emerges at the superior temporal line of the skull. Although injuries to the branches of the ECA are considerably more common than those to the main trunk of the ECA, the main trunk of the ECA is one of the most common parent arteries pertaining to the pseudoaneurysm. Bleeding from wounds is the main clinical sign after injury. Upon reviewing the existing literature, almost all patients underwent EVT using fibered coil embolization and showed good out-

(a)

(e)

(b)

(c)

(f)

(d)

(g)

Figure 1. (a) Computed tomography images with massive contrast medium extravasation (circle). (b) Angiography revealed a pseudoaneurysm (arrow) with contrast medium extravasation (arrow head) from the proximal trunk of the external carotid artery distal to the origin of the facial artery. (c) Coil embolization using an ED coil complex and the injection of N-butyl cyanoacrylate. (d) Completion of hemostasis.

Contrast-enhanced CT revealed no dilatation or disruption of the arterial wall at the external carotid artery. (e) Coronal image; (f) sagittal image. (g) The wound was healed after suturing.

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2015

9 (8)

Stab wound

Type of trauma Stable (8)

bleeding (1)

Pulsatile mass (6),

2014

7

20–40 M (7)

Gunshot (7)

Bleeding (6),

N/A

N/A

Unknown (1)

1/1 (STA)

OA and FA (1)

(2), LA (1)

IMA (3), STA

Onyx (1), Gelatin

Laceration: NBCA (4),

PA: Coils

detachable coils

or wuthout (3)

Fiberd coils with (5)

Treatment

2012

2007

Inaba et al.

Cox et al.[10]

1

8

2

1

20

N/A

N/A

20

M

N/A

N/A

M

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5 blast (6)

Gunshot (2)

Stab wound (2)

Gunshot

Pipe penetration

None

Stable (2)

Blast

Bleeding

N/A Stable (7)

N/A

Immediately

5 weeks

N/A

2 days

32

N/A

N/A

Stable (32)

N/A

stab wound

N/A

8/8

1/1

1/1

0/1

2/2

0/8

1/1

0/1

1/1

0/2

FA (10), LA (2)

ECA (10), IMA (10),

(Almost

N/A

LA (3), STA (1)

IMA (6), FA (5),

FA

IMA

IMA

ECA

The branches of

LA (1), ECA (1)

FA (2), LA (1)

ECA (2),

IMA (3),

ECA (no details)

STA

IMA

N/A

Gunshot or Bleeding

N/A

N/A

1

25

M

Bleeding

Unstable

Immediately

N/A

1/1

ECA

1/1

FA (2)

ECA (1), IMA (5),

OA

Detachable coils+NBCA

fibered coils

Ggelatin sponge or

N/A

fibered coils

Ggelatin sponge or

PVA (1), microcoils (3)

Gelatin sponge (6),

Microcoils

N/A

Fibered coils

N/A

Fibered coils

Gelatin sponge (1)

Coils (7),

N/A

NBCA

Particles

Survived

Survived (8)

N/A

Survived (30)

Dead (1)

Survived (6),

Survived

Survived

Survived

N/A

Survived (2)

Survived (8)

N/A

Survived

Survived

Dead (1)

Survived (6)

Survived (8)

Outcome

ECA: External carotid artery; FA: Facial artery; IMA: Internal maxillary artery; LA: Linguinal artery; N: Number of ICA injuries; N/A: None available; NBCA: N-butyl cyanoacrylate; PA: Pseudoaneurysm; PVA: Polyvinyl alcohol; STA: Superficial temporal artery; OA: Occipital artery.

2016

Stab wound

N/A

N/A

Present case

16–52

Stable

stab wound

8

N/A

1985

Gunshot or

N/A

Sclafani et al.[19]

1 stab wound

1996

Montalvo et al.[18]

leceration)

1996

(epistaxis)

Bleeding

Bleeding

Stable

Gunshot or

Gunshot

Gunshot

Bleeding

Sclafani et al.[17]

20–61 M (7)

M

M

7

30

41

1999

1

1

Borsa et al.[16]

[14]

2001

N/A

Delayed

2003 1 N/A N/A

Stable (2)

Germiller et al.[15]

Bleeding

Bynoe et al.

Gunshot or Gunshot

N/A

M (2) Gunshot or blast

(1), swelling (1)

2004

N/A

N/A

N/A N/A

(3), pulsatile mass

N/A

Stable (2)

9 days

Immediately

Krishnan et al.[13]

2

2

N/A None (3), bleeding

Stable Stable

sab wound

2005

Ferguson et al.[12]

Bleeding Pulsatile mass

2006

Fox et al.[11]

[9]

2014

2013

Kwon et al.[7]

Lee et al.[8]

sponge (1)

Yevich et al.[6]

STA (1)

(2), STHA (2),

5 monts

8/8

ECA (3), IMA

Existing PA

2 days-

Clinical Hemodynami Intervals Affected artery presentation after injury

F (1)

16–25 M (7),

Published n Age Sex year

Wang et al.[1]

Authors

Table 1. Review of the published literatures on penetrating ECA injuries treated by EVT

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Tsurukiri et al. Endovascular treatment of a ruptured ECA pseudoaneurysm by a cervical stab wound

comes. However, re-bleeding and facial nerve palsy after EVT were also reported.[20] Although the standard treatment is surgical ligation and resection of the ECA segment without the need for reconstruction, EVT can be considered if there is difficulty in identifying the source of bleeding for injured regions that are difficult to operatively access, particularly in deeply located vessels injured by cervical stab wounds. The development of endovascular equipment has contributed to the acceptance of EVT as an effective and safe treatment, and various embolic materials are now available. Gelatin sponge particles are divided into temporary embolic agents. Alternatively, microcoils and NBCA are divided into permanent embolic agents. The use of gelatin sponge particles or coils involves the physical blocking of blood flow with thrombus formation in the vascular lumen. NBCA is routinely used by mixing it with iodized oil to make it radiopaque, and an operator can adjust the extent of embolization by changing the mixing ratio. The use of NBCA in an animal model of hemorrhage-induced coagulopathy and various nontraumatic situations was demonstrated.[21,22] An 0.010-inch ED Coil Complex is a ready available electrical detachable coil and has a more complex outward shape and softer flexibility than conventional helical ED coils. We used these coils because the pseudoaneurysm was continuously bleeding and very fragile; coil deployment was successful.

Furthermore, we added the proximal ECA occlusion using NBCA with technically success.

Conclusion EVT appears to be an effective surgical alternative for patients with hemorrhage-induced coagulopathy caused by ruptured ECA pseudoaneurysms after cervical stab wounds.

Consent Written informed consent was obtained from the next of kin of the patient for publication of this case report and accompanying images.

Conflict of interest: None declared.

REFERENCES 1. Wang D, Su L, Han Y, Fan X. Embolization treatment of pseudoaneurysms originating from the external carotid artery. J Vasc Surg 2015;61:920–6.

2. Davis JW, Holbrook TL, Hoyt DB. Blunt carotid artery dissection: incidence, associated injuries, screening and treatment. J Trauma 1990;30:1514–417.

3. Bayır A, Aydoğdu KireşI D, Söylemez A, Demirci O. Cerebral infarction caused by traumatic carotid artery dissection. Ulus Travma Acil Cerrahi Derg 2012;18:347–50.

4. Bodanapally UK, Dreizin D, Sliker CW, Boscak AR, Reddy RP. Vascular Injuries to the Neck After Penetrating Trauma: Diagnostic Per-

436

formance of 40- and 64-MDCT Angiography. AJR Am J Roentgenol 2015;205:866–72.

5. Mattox KL, Feliciano DV, Burch J, Beall AC Jr, Jordan GL Jr, De Bakey ME. Five thousand seven hundred sixty cardiovascular injuries in 4459 patients. Epidemiologic evolution 1958 to 1987. Ann Surg 1989;209:698–7.

6. Yevich SM, Lee SR, Scott BG, Shaltoni HM, Mawad ME, Benndorf.

Emergency endovascular management of penetrating gunshot injuries to the arteries in the face and neck: a case series and review of the literature.

J NeuroIntervent Surg 2014;6:42–6.

7. Kwon B, Chang HW, Kim SJ, Sohn SL, Choi TH. Penetrating facial injury. Emerg Med J 2014;31:774.

8. Lee SR, Metwalli ZA, Yevich SM, Whigham CJ, Benndorf G. Variability in evolution and course of gunshot injuries to the neck and impact on management. A case report. Interv Neuroradiol 2013;19:489–95.

9. Inaba K, Branco BC, Menaker J, Scalea TM, Crane S, DuBose JJ, et al.

Evaluation of multidetector computed tomography for penetrating neck injury: A prospective multicenter study. J Trauma 2012;72:576–84.

10. Cox MW, Whittaker DR, Martinez C, Fox CJ, Feuerstein IM, Gillespie DL. Traumatic pseudoaneurysms of the head and neck: Early endovascular intervention. J Vasc Surg 2007;46:1227–33.

11. Fox CJ, Gillespie DL, Weber MA, Cox MW, Hawksworth JS, Cryer CM, et al. Delayed evalustion of combat-related penetrating neck trauma. J Vasc Surg 2006;44:86–93.

12. Ferguson E, Dennis JW, Vu JH, Frylberg ER. Redefining the role of arterial imaging in the management of penetrating zone 3 neck injuries. Vascular 2005;13:158–63.

13. Krishnan DG, Marashi A, Malik A. Pseudoaneurysm of internal maxillary artery secondary to gunshot wound managed by endovascular technique. J Oral Maxillofac Surg 2004;62:500–2.

14. Bynoe RP, Kerwin AJ, Parker HH, Nottingham JM, Bell RM, Yost MJ, et al. Maxillofacial injuries and life-threatening hemorrhage: treatment with transcatheter arterial embolization. J Trauma 2003;55:74–9.

15. Germiller JA, Myers LL, Harris MO, Bradford CR. Pseudoaneurysm of the proximal facial artery presenting as oropharyngeal hemorrhage. Head Neck 2001;23:259–63.

16. Borsa JJ, Fontaine AB, Eskridge JM, Song JK, Hoffer EK, Aoki AA. Transcatheter arterial embolization for intractable epistaxis secondary to gunshot wounds. J Vasc Interv Radiol 1999;10:297–302.

17. Sclafani AP, Sclafani SJ. Angiography and trancatheter arterial embolization of vascular injuries of the face and neck. Laryngoscope 1996;106:168–73.

18. Montalvo BM, LeBlang SD, Nunez DB, Ginzburg E, Klose KJ, Becerra JL, et al. Color doppler sonography in penetrating injuries of the nack.

AJNR Am J Neuroradiol 1996;17:943–51.

19. Sclafani SJ, Panetta T, Goldstein AS, Phillips TF, Hotson G, Loh J, et al.

The management of arterial injuries caused by penetrating of Zone III of the Neck. J Trauma 1985;25:871–81.

20. Rhee CS, Jinn TH, Jung HW, Sung MW, Kim KH, Min YG. Traumatic pseudoaneurysm of the external carotid artery with parotid mass and delayed facial nerve palsy. Otolaryngol Head Neck Surg 1999;121:158–60.

21. Yonemitsu T, Kawai N, Sato M, Sonomura T, Takasaka I, Nakai M, et al. Comparison of hemostatic durability between N-Butyl Cyanoacrylate and gelatin sponge particles in transcatheter arterial embolization for acute arterial hemorrhage in a coagulopathic condition in a swine model.

Cardiovasc Intervent Radiol 2010;33:1192–7.

22. Igarashi S, Izuchi S, Ogawa Y, Yoshimathu M, Takizawa K, Nakajima Y, et al. N-butyl cyanoacrylate is very effective for massive hemorrhage during the perinatal period. PLoS ONE 2013;8:e77494.

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OLGU SUNUMU - ÖZET

Servikal penetran yaranın neden olduğu eksternal karotis arter psödoanevrizması rüptürünün acil endovasküler tedavisi: Bir olgu sunumu ve literatürün gözden geçirilmesi Dr. Junya Tsurukiri,1 Dr. Eitaro Okumura,1 Dr. Hiroshi Yamanaka,1 Dr. Hiroyuki Jimbo,2 Dr. Akira Hoshiai1 1 2

Tokyo Tıp Üniversitesi Hachioji Tıp Merkezi, Acil ve Kritik Bakım Kliniği, Tokyo-Japonya Tokyo Tıp Üniversitesi Hachioji Tıp Merkezi, Nöroşirurji Kliniği, Tokyo-Japonya

Penetran yaralanmanın neden olduğu eksternal karotis arter (EKA) psödoanevrizmaları seyrek görülen bir vasküler anomalidir. Eksternal karotis arter segmentinin eksplorasyonu standart tedavi olmasına rağmen, cerrahi olarak ulaşılması zor alanda kanamanın kaynağını bulmada zorluk varsa endovasküler tedavi (EVT) düşünülebilir. Burada EKA’nın ana gövdesinde psödoanevrizmalı III. zon boyun penetran yarasının neden olduğu kanamanın neden olduğu koagülopatiyle birlikte kanaması durdurulamayan genç bir hastayı tedavi ettik. Hasta başarılı hemostazın sağlandığı EVT geçirmiştir. PubMed verilerine dayanan literatür derlemeleri sonucu EVT ile tedavi edilmiş penetran EKA yaralanmalarına ait 155 yayınlanmış olgu raporu saptanmıştır. Endovasküler tedavinin, boyunda penetran yaralanma sonrası oluşan rüptüre EKA psödoanevrizmasının yol açtığı kanamanın neden olduğu koagülopati hastalarında etkili bir alternatif cerrahi tedavi olduğu kararına vardık.

Anahtar sözcükler: Boyun; girişimsel radyoloji; kanama; penetran; silahla yaralanma; şok; yaralanma.

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CA S E REP OR T

Laparoscopic approach for removing a coin trapped in Meckel’s diverticulum Kıvılcım Karadeniz Cerit, M.D.,1 Aybegüm Kalyoncu, M.D.,1 İpek Erbarut, M.D.,2 Gürsu Kıyan, M.D.,1 Tolga Emrullah Dağlı, M.D.1 1

Department of Pediatric Surgery, Marmara University Faculty of Medicine, İstanbul-Turkey

2

Department of Pathology, Marmara University Faculty of Medicine, İstanbul-Turkey

ABSTRACT Foreign body ingestion is a common problem in children. Most of these foreign bodies spontaneously pass through the gastrointestinal tract.When there is a persistent foreign body in the abdomen, it is impossible to make a diagnosis without exploration.We herein present the case of a child who was admitted to our hospital with a coin trapped in Meckel’s diverticulum and our laparoscopic approach in this case. The diagnosis of Meckel’s diverticulum should be considered when there is a prolonged lodgment of a foreign body in the right lower quadrant, and the laparoscopic approach is the preferred choice in these cases.

Keywords: Child; coin; Meckel’s diverticulum.

INTRODUCTION Foreign body ingestion is a common problem among children.

Most foreign bodies that have passed the esophagus will pass uneventfully through the intestinal tract. Foreign bodies that remain blocked in the narrower segments of the digestive tract (10–20%) require nonsurgical intervention, and ≤1% of them require surgical intervention.[1,2] The nature of the foreign body is important for management. Foreign bodies with smooth edges usually do not cause a serious situation, but urgent intervention is required if the foreign body is a sharp object.[1] The decision for intervention is difficult in cases with prolonged lodgment.

We herein report the case of an asymptomatic child who presented with a coin trapped in Meckel’s diverticulum. To the best of our knowledge, there are no prior reports on coins (Poster presentation in 31. National Pediatric Surgery Congress, 2013).

Address for correspondence: Kıvılcım Karadeniz Cerit, M.D. Fevzi Çakmak Mah., Mimar Sinan Cad., No: 41, Üst Kaynarca, Pendik İstanbul, Turkey Tel: +90 216 - 421 22 22 E-mail: kcerit@yahoo.com Submitted: 02.10.2015 Accepted: 06.12.2016

Ulus Travma Acil Cerrahi Derg 2017;23(5):438–440 doi: 10.5505/tjtes.2016.13265 Copyright 2017 TJTES

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trapped in Meckel’s diverticulum and the use of the laparoscopic approach for it in the pediatric literature.

CASE REPORT A 10-year-old boy was admitted to our hospital for the removal of an intestinal foreign body with 3 months history. There was no history of coin ingestion, but the foreign body appeared to be a coin located in the right lower quadrant in the abdominal X-ray (Fig. 1). The coin was incidentally discovered while evaluating his hip dysplasia. On performing a physical examination, the patient showed no abdominal tenderness. Laboratory data were normal. Colonoscopy was performed by pediatric gastroenterologists to evaluate the foreign body, but the coin was not identified in the colon. The possibility that the coin was located in the distal bowel or lodged in Meckel’s diverticulum was considered. Fluoroscopy-guided laparoscopy was performed to locate the coin. The search for the coin was started at the ileocecal valve and continued proximally through the small bowel.

Meckel’s diverticulum was identified 50 cm proximal to the ileocecal valve. The coin was detected in Meckel’s diverticulum by fluoroscopy-guided laparoscopy, and Meckel’s diverticulum was moved into the upper abdomen to examine. Segmental resection of the ileum including Meckel’s diverticulum and end-to-end anastomosis were performed. An examination of the resected specimen revealed the coin trapped in Meckel’s diverticulum (Fig. 2). After the operation, the patient had an uneventful recovery and started enteral feeding within 3 days.

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Karadeniz Cerit et al. Laparoscopic approach for removing a coin trapped in Meckel’s diverticulum

DISCUSSION Foreign body ingestion is a common problem in the pediatric population; its early diagnosis and intervention is essential because some ingested foreign bodies may cause serious complications such as mucosal erosion, airway obstruction, and intestinal perforation.[1] Enteroscopy or surgery should be

Figure 1. Abdominal radiograph revealing a metallic foreign body in the pelvis.

considered for the removal of dangerous foreign bodies such as sharp, pointed or long objects, batteries, or magnets that have passed the angle of Treitz. For foreign bodies that have a lower risk of causing perforation such as coins, daily stool observation and X-ray images are required to estimate the progression of foreign bodies through the gastrointestinal tract.

However, patient should be aware of the clinical signs of perforation during this period.[2] Coins are the most frequently ingested foreign bodies in Western countries in the pediatric population. Although coins impact through the esophagus in 30–40% of cases, children may remain asymptomatic.[2] The determination of the exact location of the coin, decision for intervention, and management may be difficult in cases with prolonged lodgment. Locating coins is not easy via X-ray images in such cases. Coins should be differentiated from batteries using the border aspect (smooth or irregular for coins and two concentric circles for batteries).[2] Most foreign bodies that reach the gastrointestinal tract spontaneously pass through it.[1] However, foreign bodies can get stuck in congenital intraluminal abnormalities such as windsock anomalies, anatomical structures including Meckel’s diverticulum, appendix vermiformis, or previous anastomosis sites.[3] Meckel’s diverticulum is the most common congenital anomaly in the gastrointestinal tract and is found in 2% of the general population. Meckel’s diverticulum can be symptomatic with infection, bleeding, and intestinal obstruction. There are several cases in the pediatric and adult literature reporting on perforation or obstruction of Meckel’s diverticulum by button batteries, phytobezoars, fish bones, chicken bones, wood splinters, needle, pins, or liberty bell.[4–7] Entrapment of a coin in Meckel’s diverticulum in a child is extremely rare, and to the best of our knowledge, there are no prior reports on this in the US National Library of Medicine National Institutes of Health (PubMed) database. Only one report was found in the EBSCO Database, but the laparoscopic approach was not performed. Purkayastha et al. reported the case of a 19-month-old patient with intermittent bouts of abdominal pain and vomiting. The patient’s X-ray revealed a coin in the right lower quadrant; laparotomy was performed and the coin was found in Meckel’s diverticulum.[8] Halverson et al. reported perforation of Meckel’s diverticulum by a coin was ingested by an adult patient.[9] Surgical intervention is indicated in cases of radiographic evidence of the failure of the coin to progress through the gastrointestinal tract. The diagnosis of Meckel’s diverticulum should be considered when there is a persistent foreign body in the right lower quadrant. It is impossible to make the diagnosis without exploration of the abdomen. The laparoscopic approach is the preferred noninvasive treatment choice for identifying and managing these cases.

Figure 2. Coin located within Meckel’s diverticulum.

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Conflict of interest: None declared.

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REFERENCES 1. Aydoğdu S, Arikan C, Cakir M, Baran M, Yüksekkaya HA, Saz UE, et al.

Foreign body ingestion in Turkish children. Turk J Pediatr 2009;51:127– 32.

2. Chauvin A, Viala J, Marteau P, Hermann P, Dray X. Management and endoscopic techniques for digestive foreign body and food bolus impaction. Dig Liver Dis 2013;45:529–42.

3. Yalçin S, Karnak I, Ciftci AO, Senocak ME, Tanyel FC, Büyükpamukçu N. Foreign body ingestion in children: an analysis of pediatric surgical practice. Pediatr Surg Int 2007;23:755–61.

4. Escobar MA, Tiu MC, Yotter CN, Han MT. Button battery perforating a Meckel’s diverticulum in an asymptomatic child: An exception to recommendations for management. Journal of Pediatric Surgery Case Reports

2013;6:132–5.

5. Karaman A, Karaman I, Erdoğan D, Cavuşoğlu YH, Aslan MK, Varlikli O, et al. Perforation of Meckel’s diverticulum by a button battery: report of a case. Surg Today 2007;37:1115–6.

6. Mares AJ, Finaly R, Mordechai J, Motovic A. “Pantaloon” phytobezoar: an unusual cause of intestinal obstruction associated with Meckel’s diverticulum. Isr J Med Sci 1993;29:683–5.

7. Roessel CW. Perforation of meckel’s diverticulum by foreign body: case report and review of the literature. Ann Surg 1962;156:972–5.

8. Purkayastha A, DeWitt W, Koberlein N. Foreign body in a Meckel’s diverticulum. JAMA 1984;251:2659.

9. Halverson JM, Butterman MK, Legier JF, Mann WJ Jr, Hoefer RA Jr. Perforation of a Meckel’s diverticulum caused by ingestion of a coin.

South Med J 1994;87:823–4.

OLGU SUNUMU - ÖZET

Meckel divertikülü içine hapsolmuş bozuk para olgusuna laparoskopik yaklaşım Dr. Kıvılcım Karadeniz Cerit,1 Dr. Aybegüm Kalyoncu,1 Dr. İpek Erbarut,2 Dr. Gürsu Kıyan,1 Dr. Tolga Emrullah Dağlı1 1 2

Marmara Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, İstanbul Marmara Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, İstanbul

Yabancı cisim yutulması çocukluk çağında sık görülen bir acil durumudur. Bu cisimlerin çoğu gastrointestinal sistemden herhangi bir sorun olmadan geçer. Karında devamlı aynı yerde sebat eden bir yabancı cisim olduğunda ise eksplorasyon yapmadan tanıyı koymak imkansızdır. Bu yazıda, kliniğimize başvuran Meckel divertikülünde para hapsolmuş bir olgu ve bu olguya laparoskopik yaklaşımımız sunulmuştur. Sağ alt kadranda uzun süre sebat eden bir yabancı cisim varlığında Meckel divertikülü tanısı ve laparoskopik yaklaşım seçeneği göz önünde bulundurulmalıdır.

Anahtar sözcükler: Çocuk; Meckel divertikülü; bozuk para.

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CAS E R EP O RT

Role of percutaneous transhepatic biliary drainage in the management of blunt liver trauma: A case report Şükrü Oğuz, M.D., Reyyan Yıldırım, M.D., Serdar Topaloğlu, M.D. Department of Radiology, Karadeniz Technical University, Farabi Hospital, Trabzon-Turkey

ABSTRACT The liver is the most commonly injured intra-abdominal organ after blunt trauma. The management of massive liver injury is complex.

Percutaneous transhepatic biliary drainage is the first approach considered, particularly for proximal bile duct strictures after liver surgery. A 27-year-old female patient was transferred to our emergency department with grade V blunt injury. Regarding the patient’s unresponsive hemodynamic instability, right hepatectomy was performed.The patient presented with benign biliary duct stricture after surgery that were treated via the percutaneous approach.

Keywords: Benign biliary stricture; liver injury; percutaneous approach.

INTRODUCTION The liver is the most commonly injured intra-abdominal organ after blunt trauma.[1] The management of massive liver injury is complex. A decision on whether the operative or non-operative approach to liver injury should be used largely depends on the experience of the management team. Biliary duct injury is rare complication encountered after hepatic surgery.[2] Percutaneous transhepatic biliary drainage (PTBD) is the first approach considered, particularly for proximal bile duct strictures.[3] A multidisciplinary approach is required for managing patients.

Here we present the case of a patient with massive liver trauma who was managed with surgical and interventional radiology teams.

CASE REPORT A 27-year-old female was admitted to the emergency department with multiple traumas after a traffic accident. EnAddress for correspondence: Şükrü Oğuz, M.D. Karedeniz Teknik Üniversitesi, Farabi Hastanesi, Radyoloji Anabilim Dalı, Trabzon, Turkey Tel: +90 462 - 377 12 34 E-mail: drsukruoguz@gmail.com Submitted: 30.09.2016 Accepted: 07.02.2017

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dotracheal intubation and tube drainage of the right thorax were performed at the site where the accident took place.

Her past medical history was unremarkable. Her physical examination revealed resistant hypotension, tachycardia, abdominal distention, deformities on the left lower and left upper extremities, and maxillofacial trauma.

The hemoglobin level was 6 g/dl, and hematocrit was 17.8%.

Computed tomography (CT) in the emergency department revealed nasal fracture, multiple fractures in the right and left orbital spaces, a left mandibular fracture, a fracture in the posterior wall of left maxillary sinus, right hemothorax, and grade V blunt liver injury (according to the 1994 revision of organ injury scaling by Moore et al.[4]), and intra-abdominal bleeding (Fig. 1). Because of the patient’s unresponsive hemodynamic instability, laparotomy was performed. Right hepatectomy with repair of injury of the main portal vein was required for achieving hemostasis. The stabilization of extremity fractures (a fracture in the distal part of the left femoral shaft, fracture in the left pelvic ramus, and fractures in the left forehand) was also performed in the operation.

The patient received 6 units of erythrocyte suspension and 8 units of fresh frozen plasma (FFP) during the operation.

Re-exploration was required 8 h after the initial operation because of the persistent bleeding from the abdominal drains. Hemostasis of the raw surface of the remnant liver with additional sutures was achieved during re-laparotomy.

During the initial 24 h period after the trauma, the patient underwent massive transfusion: 11 units of erythrocyte suspension, 24 units of FFP, and 1 unite of thrombocyte suspension. The patient was followed up under ventilation support with anti-edema medications, anti-epileptic medications, and 441

Oğuz et al. Role of percutaneous transhepatic biliary drainage in the management of blunt liver trauma

ceftriaxone-metronidazole antibiotic treatment. Parenteral bicarbonate replacement was started on the third postoperative day (POD) because of the presence of myoglobinuria.

Elevated the international normalized ratio (INR) (>2) was observed on the fourth POD. After controlling the patency of vascular and biliary structures of the remnant liver with ultrasound, plasma exchange treatment (with 10 units of FFP per day) was started for the treatment of postoperative liver failure. Extubation was achieved on the seventh POD. Enteral feeding was started on the eighth POD. Normalization of INR was achieved with daily plasma exchange in the second postoperative week. However, increment in total and direct bilirubin levels during plasma exchange was noted.

Abdominal CT on the 14th POD revealed biliary dilatation in the remnant liver (Fig. 2a).

To decompress the biliary duct, PTBD was planned. The remnant left bile ducts were punctured using a 22-G needle via the subxiphoid approach with ultrasound guidance to perform percutaneous cholangiography (PTC). Initial percutaneous transhepatic cholangiogram revealed a high-grade Strasberg type E4 stricture of the left hepatic duct and no contrast medium passage distally. Then, an 8-F external biliary drainage catheter was placed proximal to the level of obstruction (Fig. 2b). In the second-look cholangiography two weeks later, total obstruction of the left hepatic bile duct persisted. In the third-look cholangiography on month later, passage of the

minimally contrast medium distally to common hepatic duct and a niche in the most distal tip of the left hepatic duct were observed. This niche was considered as the obstruction level; therefore, an attempt was made to pass it using a standard 0.035” hydrophilic guide wire (0.035 Radiofocus® Guidewire, Terumo Corp., Somerset, NJ, USA). Because of the failure to pass the obstruction with the standard 0.035” hydrophilic guide wire, a microcatheter (Progreat, Terumo Corp., Somerset, NJ, USA) with its standard microwire (0.018”) was used.

However, this could not be passed with standard peripheral micromaterials. For this reason, this was attempted to pass obstruction using a neurointervention-dedicated microguidewire (X-Pedion-14 (0.0014”), Ev3 Micro Therapeutics Inc., CA, USA). The last attempt with this micro-guidewire resulted in successful passing. Finally, an 8-F internal-external biliary drainage catheter was placed.

The internal-external biliary drainage catheter was oversized to a 10 F catheter after one month. Because of the sustained stricture after three months of follow-up, the stricture was dilated twice using 6-8 conventional angioplasty balloon catheters at intervals of two weeks. The internal-external biliary drainage catheter was replaced by an external biliary drainage catheter, and it was closed to evaluate the success (Fig. 3). When laboratory test results and biliary passage were normal after two weeks, the external biliary drainage catheter was removed.

Figure 1. Axial contrast-enhanced CT images showing hypodense areas in multiple segments of the liver, indicating grade V liver injury.

(a)

(b)

Figure 2. (a) Axial non-contrast CT image showing dilatation of the left biliary duct. (b) Initial percutaneous transhepatic cholangiogram showing a high-grade Strasberg type E4 stricture of the left hepatic duct and no contrast medium passage distally.

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(a)

(b)

(c)

Figure 3. (a) Control percutaneous transhepatic cholangiogram showing the sustained stricture after three months. (b) A stiff guide wire was placed using an internal-external biliary drainage catheter, and the balloon was inflated at the level of the stricture. (c) The stricture was successfully dilated.

DISCUSSION An iatrogenic bile duct structure is a rare complication that occurs after gastrointestinal surgery; its prevalence is continuously increasing. Primary causes of IBDSs are bile duct surgery such as open and laparoscopic cholecystectomy (the most common reason), choledochotomy, and previous surgery on the bile duct. Hepatic resection, liver transplantation, gastric resection, pancreatic resection and biloenteric anastomosis are rarer reasons. Direct bile duct trauma, thermal injury as a result of over-cauterization, ischemia of the bile duct secondary to vascular injury, and incorrectly placed vascular clips may cause stricture during such major surgical operations.[2,5–8] The selective non-operative management of blunt liver trauma has become the standard of care. However, hemodynamic stability and no signs of peritonitis are absolute requirements in the non-operative management. In approximately 80% to 85% of patients undergoing operative management, the liver injury can be managed by relatively simple surgical techniques such as the application of local hemostatic agents, electrocoagulation, superficial suturing, or closed drains.[1] The remaining 15% to 20 % of cases are associated with extensive parenchymal damage not amenable to deep suturing or perihepatic packing. Non-anatomic or anatomic resection of the injured liver may be required for hemostasis or preventing subsequent necrosis and sepsis or delayed hemorrhage. In the hands of experienced hepatobiliary surgeons, liver resection for trauma is associated with acceptable morbidity and mortality rates.[9–11] The incidence of postoperative liver-related complications in patients surviving with severe liver injuries (grade III-IV) has been reported to be nearly 50%.[12] These complications include early or late hemorrhage, liver necrosis, liver failure, liver abscess, false aneurysms, arteriovenous fistulas, bilomas, biliary fistulas, hemobilia, and biliary strictures.[1,9–12] Liver failure is generally transient in patients without huge liver necrosis, and liver functions are improved within 2 to 3 weeks supportive treatment, which was similar to that seen in our case.[13] Resistant hyperbilirubinemia or biliary fistula during the early postoperative period after liver resection always Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5

indicates biliary duct obstruction. The necessity of the rapid control and ligation of hepatic inflow/outflow structures belonged to remove liver lobe is a major concern in trauma surgery in contrast to elective liver resections. Control of biliary duct patency is generally the secondary goal in patients with hemodynamic instability. Mass ligation of hilar structures may be associated with kinking of the extrahepatic biliary duct.

The reported incidence of postoperative biliary complications increases with the severity of liver injury.[14] IBDSs rare treated by surgical, endoscopic, or percutaneous approaches and non-invasive approaches are recommended as the first options.[2,15] Although, endoscopic retrograde cholangiopancreatography (ERCP) is the first recommended treatment option, proximal bile duct strictures and gastrointestinal surgery procedures (such as Roux-en Y hepaticojejunostomy), which do not permit access, are the main limiting factors.[16,17] PTC is superior for proximal bile duct strictures and common bile duct or right aberrant hepatic bile duct injury than ERCP.[3] The percutaneous approach is the first choice of treatment in situations the following situations: avoiding a second surgical procedure, failure of ERCP, complete ductal ligation or trans-section, proximal bile duct strictures, or requirement of immediate decompression of the biliary duct.[15] However, there is no consensus on how benign bile strictures should be treated, including the optimal duration of biliary drainage or balloon dilatation, the size of the drainage catheter, the frequency of procedures, the size and type of balloons or the usage of stents.[18] The optimal duration of biliary drainage is unclear, although it is more than four months associated with improved ductal patency.[19] Technically, success is considered when there is residual stenosis of 30% or less after balloon dilatation.[18] The biliary drainage catheter is pulled back proximal to the stricture and is closed to check the success. If a patient is asymptomatic and laboratory test results are normal in the following 7–10 days, the biliary drainage catheter is removed. Long term patency has been reported in 33–90% of cases using this technique.[18,20]

Conclusion In case of traumatic fragile livers, the first point of PTC that needs to be considered is that the bile duct should be punctured using a 21 G or smaller needle with ultrasound guidance. The drainage catheter should be placed as gently as possible. The priority should be bile drainage, and the stricture should be attempted to be passed in later session in the event of major liver surgery or trauma. The stricture should not be forced with excessive maneuvers in fragile livers to avoid undesirable complications of PTBD. Repeat cholangiography with reasonable intervals can resolve the occlusion through hints such as passing of the contrast medium or observing a niche. Furthermore, the materials used in intravascular procedures, with the knowledge and experience gained in this area, can help in solving problems in nonvascular procedures.

Conflict of interest: None declared.

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Oğuz et al. Role of percutaneous transhepatic biliary drainage in the management of blunt liver trauma

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OLGU SUNUMU - ÖZET

Karaciğer künt travma yönetiminde perkütan biliyer drenajın rolü: Olgu sunumu Dr. Şükrü Oğuz, Dr. Reyyan Yıldırım, Dr. Serdar Topaloğlu Karadeniz Teknik Üniversitesi, Farabi Hastanesi, Radyoloji Anabilim Dalı, Trabzon

Künt travma sonrası, çoğunlukla yaralanan karın içi organ karaciğerdir. Karaciğer masif yaralanma yönetimi kompleks bir durumdur. Karaciğer cerrahisi sonrası gelişen özellikle proksimal biliyer duktus striktürlerinde perkütanöz transhepatik biliyer drenaj göz önünde bulundurulması gereken ilk yaklaşımdır. Acil servisimize grade V karaciğer yaralanması olan, 27 yaşında bir kadın hasta transfer edildi. Hemodinamik olarak değişken olan hastaya sağ hepatektomi yapıldı. Cerrahi sonrası hasta, biliyer duktusda benign striktür ile başvurdu ve bu durum perkütanöz yaklaşımla tedavi edildi.

Anahtar sözcükler: Benign biliyer striktür, karaciğer yaralanması; perkütanöz yaklaşım.

Ulus Travma Acil Cerrahi Derg 2017;22(5):441–444

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doi: 10.5505/tjtes.2017.52196

Ulus Travma Acil Cerrahi Derg, September 2017, Vol. 23, No. 5