TRAUMA 2017 / 4 by KAREPUBLISHING

ISSN 1306 - 696X

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

Bayraktar A, et al. p. 351

Volume 23 | Number 4 | July 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) Kaya Sarıbeyoğlu Vice President (2. Başkan) M. Mahir Özmen Secretary General (Genel Sekreter) Hakan Yanar Treasurer (Sayman) Ali Fuat Kaan Gök Members (Yönetim Kurulu Üyeleri) Osman Şimşek Orhan Alimoğlu

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

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

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

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

p-ISSN 1306-696x • e-ISSN 1307-7945 • Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır.) Publisher (Yayımcı): KARE Yayıncılık (KARE Publishing) • www.kareyayincilik.com • Design (Tasarım): Ali Cangül • Graphics (Grafikler): Edibe Çomaktekin • Linguistic Editor (İngilizce Editörü): Suzan Atwood • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): July (Temmuz) 2017 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

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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 2008 in Index Copernicus. Our impact factor in SCI-E indexed journals is 0.5. It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PUBMED.

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

Submission of a manuscript by electronic means implies: that the work has not been published before (except in the form of an abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; and that its publication in the Turkish Journal of Trauma and Emergency Surgery is approved by all co-authors. The author(s) transfer(s) the copyright to the Turkish Association of Trauma and Emergency Surgery to be effective if and when the manuscript is accepted for publication. The author(s) guarantee(s) that the manuscript will not be published elsewhere in any other language without the consent of the Association. If the manuscript has been presented at a meeting, this should be stated together with the name of the meeting, date, and the place. Manuscripts may be submitted in Turkish or in English. All submissions are initially reviewed by the editor, and then are sent to reviewers. All manuscripts are subject to editing and, if necessary, will be returned to the authors for answered responses to outstanding questions or for addition of any missing information to be added. For accuracy and clarity, a detailed manuscript editing is undertaken for all manuscripts accepted for publication. Final galley proofs are sent to the authors for approval. Unless specifically indicated otherwise at the time of submission, rejected manuscripts will not be returned to the authors, including accompanying materials. TJTES is indexed in Science Citation Index-Expanded (SCI-E), Index Medicus, Medline, EMBASE, Excerpta Medica, and the Turkish Medical Index of TUBITAK-ULAKBIM. Priority of publications is given to original studies; therefore, selection criteria are more refined for reviews and case reports. Open Access Policy: Full text access is free. There is no charge for publication or downloading the full text of printed material. Manuscript submission: TJTES accepts only on-line submission via the official web site (please click, www.travma.org.tr/en) and refuses printed manuscript submissions by mail. All submissions are made by the on-line submission system called Journal Agent, by clicking the icon “Online manuscript submission” at the above mentioned web site homepage. The system includes directions at each step but for further information you may visit the web site (http://www.travma.org/en/ journal/). Manuscript preparation: Manuscripts should have double-line spacing, leaving sufficient margin on both sides. The font size (12 points) and style (Times New Roman) of the main text should be uniformly taken into account. All pages of the main text should be numbered consecutively. Cover letter, manuscript title, author names and institutions and correspondence address, abstract in Turkish (for Turkish authors only), and title and abstract in English are uploaded to the Journal Agent system in the relevant steps. The main text includes Introduction, Materials and Methods, Results, Discussion, Acknowledgments, References, Tables and Figure Legends. The cover letter must contain a brief statement that the manuscript has been read and approved by all authors, that it has not been submitted to, or is not under consideration for publication in, another journal. It should contain the names and signatures of all authors. The cover letter is uploaded at the 10th step of the “Submit New Manuscript” sec-

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

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

YAZARLARA BİLGİ Ulusal Travma ve Acil Cerrahi Dergisi, Ulusal Travma ve Acil Cerrahi Derneği’nin yayın organıdır. Travma ve acil cerrahi hastalıklar konularında bilimsel birikime katkısı olan klinik ve deneysel çalışmaları, editöryel yazıları, klinik olgu sunumlarını ve bu konulardaki teknik katkılar ile son gelişmeleri yayınlar. Dergi iki ayda bir yayınlanır. Ulusal Travma ve Acil Cerrahi Dergisi, 2001 yılından itibaren Index Medicus ve Medline’da, 2005 yılından itibaren Excerpta Medica / EMBASE indekslerinde, 2007 yılından itibaren Science Citation Index-Expanded (SCI-E) ile Journal Citation Reports / Science Edition uluslararası indekslerinde ve 2008 yılından itibaren Index Copernicus indeksinde yer almaktadır. 2015 yılında SCI-E kapsamında İmpakt faktörümüz 0,5 olmuştur. Dergide araştırma yazılarına öncelik verilmekte, bu nedenle derleme veya olgu sunumu türündeki yazılarda seçim ölçütleri daha dar tutulmaktadır. PUBMED’de dergi “Ulus Travma Acil Cerrahi Derg” kısaltması ile yer almaktadır. Dergiye yazı teslimi, çalışmanın daha önce yayınlanmadığı (özet ya da bir sunu, inceleme, ya da tezin bir parçası şeklinde yayınlanması dışında), başka bir yerde yayınlanmasının düşünülmediği ve Ulusal Travma ve Acil Cerrahi Dergisi’nde yayınlanmasının tüm yazarlar tarafından uygun bulunduğu anlamına gelmektedir. Yazar(lar), çalışmanın yayınlanmasının kabulünden başlayarak, yazıya ait her hakkı Ulusal Travma ve Acil Cerrahi Derneği’ne devretmektedir(ler). Yazar(lar), izin almaksızın çalışmayı başka bir dilde ya da yerde yayınlamayacaklarını kabul eder(ler). Gönderilen yazı daha önce herhangi bir toplantıda sunulmuş ise, toplantı adı, tarihi ve düzenlendiği şehir belirtilmelidir. Dergide Türkçe ve İngilizce yazılmış makaleler yayınlanabilir. Tüm yazılar önce editör tarafından ön değerlendirmeye alınır; daha sonra incelenmesi için danışma kurulu üyelerine gönderilir. Tüm yazılarda editöryel değerlendirme ve düzeltmeye başvurulur; gerektiğinde, yazarlardan bazı soruları yanıtlanması ve eksikleri tamamlanması istenebilir. Dergide yayınlanmasına karar verilen yazılar “manuscript editing” sürecine alınır; bu aşamada tüm bilgilerin doğruluğu için ayrıntılı kontrol ve denetimden geçirilir; yayın öncesi şekline getirilerek yazarların kontrolüne ve onayına sunulur. Editörün, kabul edilmeyen yazıların bütününü ya da bir bölümünü (tablo, resim, vs.) iade etme zorunluluğu yoktur. Açık Erişim İlkesi: Tam metinlere erişim ücretsizdir. Yayınlanan basılı materyali tam metni indirmek için herhangi bir ücret alınmaz. Yazıların hazırlanması: Tüm yazılı metinler 12 punto büyüklükte “Times New Roman” yazı karakterinde iki satır aralıklı olarak yazılmalıdır. Sayfada her iki tarafta uygun miktarda boşluk bırakılmalı ve ana metindeki sayfalar numaralandırılmalıdır. Journal Agent sisteminde, başvuru mektubu, başlık, yazarlar ve kurumları, iletişim adresi, Türkçe özet ve yazının İngilizce başlığı ve özeti ilgili aşamalarda yüklenecektir. İngilizce yazılan çalışmalara da Türkçe özet eklenmesi gerekmektedir. Yazının ana metnindeyse şu sıra kullanılacaktır: Giriş, Gereç ve Yöntem, Bulgular, Tartışma, Teşekkür, Kaynaklar, Tablolar ve Şekiller. Başvuru mektubu: Bu mektupta yazının tüm yazarlar tarafından okunduğu, onaylandığı ve orijinal bir çalışma ürünü olduğu ifade edilmeli ve yazar isimlerinin yanında imzaları bulunmalıdır. Başvuru mektubu ayrı bir dosya olarak, Journal Agent sisteminin “Yeni Makale Gönder” bölümünde, 10. aşamada yer alan dosya yükleme aşamasında yollanmalıdır. Başlık sayfası: Yazının başlığı, yazarların adı, soyadı ve ünvanları, çalışmanın yapıldığı kurumun adı ve şehri, eğer varsa çalışmayı destekleyen fon ve kuruluşların açık adları bu sayfada yer almalıdır. Bu sayfaya ayrıca “yazışmadan sorumlu” yazarın isim, açık adres, telefon, faks, mobil telefon ve e-posta bilgileri eklenmelidir. Özet: Çalışmanın gereç ve yöntemini ve bulgularını tanıtıcı olmalıdır. Türkçe özet, Amaç, Gereç ve Yöntem, Bulgular, Sonuç ve Anahtar Sözcükler başlıklarını; İngilizce özet Background, Methods, Results, Conclusion ve Key words başlıklarını içermelidir. İngilizce olarak hazırlanan çalışmalarda da Türkçe özet yer almalıdır. Özetler başlıklar hariç 190210 sözcük olmalıdır. Tablo, şekil, grafik ve resimler: Şekillere ait numara ve açıklayıcı bilgiler ana metinde ilgili bölüme yazılmalıdır. Mikroskobik şekillerde resmi açıklayıcı bilgilere ek olarak, büyütme oranı ve kullanılan boyama tekniği de belirtilmelidir. Yazarlara ait olmayan, başka kaynaklarca daha önce yayınlanmış tüm resim, şekil ve tablolar için yayın hakkına sahip kişiler-

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

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

Number - Sayı 4 July - Temmuz 2017

Contents - İçindekiler Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 273-278 Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model: An experimental study Cordycepin’in sıçan modelinde karıniçi adezyonun ameliyat sonrası önleyici etkisi: Deneysel çalışma Arslan S, Zeytun H, Basuguy E, İbiloğlu İ, Uygun İ, Yılmaz A, Tan İ, Toprak G 279-286 Protective effects of dexmedetomidine and remote ischemic preconditioning on renal ischemia reperfusion injury in rats Deksmedetomidin ve uzak iskemik ön koşullamanın sıçanlarda renal iskemi reperfüzyon hasarı üzerine koruyucu etkileri Balcı C, Akan M, Boztaş N, Özkardeşler S, Ergür BU, Güneli ME, Ünal B 287-293 Comparison of warm fluid and cold fluid resuscitation during uncontrolled hemorrhagic shock model in rats Sıçanlarda oluşturulan kontrolsüz hemorajik şok modelinde ılık sıvı ile soğuk sıvı resüsitasyonlarının karşılaştırılması Dilmen S, Eryılmaz M, Balkan SM, Serdar M, Durusu M, Yıldırım AO, Dilmen SA

Original Articles - Orijinal Çalışma 294-300 The value of internal jugular vein collapsibility index in sepsis Internal juguler ven kollabsibilite indeksinin sepsisteki değeri Haliloğlu M, Bilgili B, Kararmaz A, Cine İ 301-305 Prognostic factors in acute mesenteric ischemia and evaluation with Mannheim Peritonitis Index and platelet-to-lymphocyte ratio Akut mezenter iskemide prognostik faktörler ve Mannheim peritonit indeksi ve trombosit/lenfosit oranı ile değerlendirilmesi Yılmaz EM, Cartı EB 306-310 Esophageal button battery ingestion in children Çocuklarda özofagus yerleşimli disk pil yutmaları Şencan A, Genişol İ, Hoşgör M 311-316 Eight years of clinical experience with digit replantation: Demographic characteristics and outcomes Parmak replantasyonları ile ilgili sekiz yıllık klinik deneyim: Demografik özellikler ve sonuçlar Oruç M, Gürsoy K, Özer K, Çolak Ö, Kankaya Y, Sungur N, Ulusoy GM, Koçer U 317-321 Ischemia-modified albumin and other inflammatory markers in the diagnosis of appendicitis in children İskemi modifiye albümin ve diğer enflamatuvar belirteçlerin çocuk apandisit tanısındaki yeri Nazik S, Avci V, Küskü Kiraz Z 322-327 Damage control surgery: 6 years of experience at a level I trauma center Hasar kontrol cerrahisi: Birinci seviye travma merkezinde altı yıllık deneyim Gupta A, Kumar S, Sagar S, Sharma P, Mishra B, Singhal M, Misra MC

Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

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

Number - Sayı 4 July - Temmuz 2017

Contents - İçindekiler

328-336 Use of trauma scoring systems to determine the physician’s responsibility in cases of traumatic death with medical malpractice claim Tıbbi uygulama hatası iddiası olan travmatik ölümlerde hekim sorumluluğunun belirlenmesinde travma skoru sistemlerinin kullanılması Arslan MN, Kertmen Ç, Melez DO, Evcüman D, Büyük Y 337-342 Total hip arthroplasty for acetabular fractures: “Early Application” Asetabulum kırıklarında total kalça protezi Salar N, Bilgen MS, Bilgen ÖF, Ermutlu C, Eken G, Durak K 343-347 Is intact fibula a disadvantage in treatment of tibial diaphysis fracture with intramedullary nailing? Tibia kırığının intramedüller çivi ile tedavisinde, intakt fibula dezavantaj mıdır? Kabukçuoğlu Y, Sökücü S, Özcan Ç, Beng K, Lapçin O, Demir B

Case Reports - Olgu Sunumu 348-350 Removal of cardiothoracic war-related shrapnel using video-assisted thoracoscopic surgery Savaş yaralanmalarından kalan kardiyotorasik şarapnellerin çıkartılması video yardımlı torakoskopik cerrahi yoluyla Khalifa M, Abu-Zidan FM, Khan N, Black E 351-353 A rare cause of hemoperitoneum: A case report of ruptured ileocolic artery aneurysm Nadir görülen bir hemoperitonium nedeni: İleokolik arter anevrizma rüptürü olgu sunumu Bayraktar A, Gök K, Yanar F, Canbay Torun B, Ertekin C 354-356 Successful endoscopic treatment of an unusual foreign body in the stomach: A package of heroin Midede olağandışı bir yabancı cismin başarılı olarak endoskopik yöntemle tedavisi: Bir eroin paketi Asıl M, Dertli R

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EXPERIMENTAL STUDY

Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model: An experimental study Serkan Arslan, M.D.,1 Hikmet Zeytun, M.D.,1 Erol Basuguy, M.D.,1 İbrahim İbiloğlu, M.D.,2 İbrahim Uygun, M.D.,1 Ahmet Yılmaz, M.D.,3 İlhan Tan, M.D.,4 Gülten Toprak, M.D.5 1

Department of Pediatric Surgery, Dicle University Faculty of Medicine, Diyarbakır-Turkey

Department of Pathology, Dicle University Faculty of Medicine, Diyarbakır-Turkey

Department of Family Medicine, Dicle University Faculty of Medicine, Diyarbakır-Turkey

Department of Pediatrics, Dicle University Faculty of Medicine, Diyarbakır-Turkey

Department of Biochemistry, Dicle University Faculty of Medicine, Diyarbakır-Turkey

ABSTRACT BACKGROUND: The aim of the present study was to investigate whether cordycepin prevented adhesion formation in a rat model. METHODS: Rats were randomly assigned to 3 groups of 10 rats. Control group: The absence of adhesion was confirmed via laparotomy. Adhesion group: The cecum was removed from the abdomen and scraped with a dry gauze bandage until petechial hemorrhagic foci developed. Cordycepin group: The same surgical procedure was performed as in the adhesion group, and 10 mg/kg cordycepin was administered intraperitoneally. After 15 days, the rats were sacrificed humanely via cardiac blood withdrawal under anesthesia. The rats were then analyzed morphologically and histopathologically, and hydroxyproline (OH-p) and malondialdehyde (MDA) levels were measured. RESULTS: Macroscopic analysis revealed significantly less adhesion in the cordycepin group than in the adhesion group (p<0.01). Furthermore, significant histopathological improvement was also evident in the cordycepin group compared to the adhesion group (p<0.05). The levels of OH-p and MDA in blood and tissue were higher in the adhesion group than in the control group, and lower in the cordycepin group than the adhesion group. Interestingly, MDA level was significantly lower (blood: p<0.05; tissue: p<0.01) in the cordycepin group than in the adhesion group, whereas only tissue OH-p was significantly lower in the cordycepin group compared with the adhesion group (p<0.05). One rat in both adhesion group and cordycepin group died postoperatively. CONCLUSION: Results indicated that cordycepin effectively reduced adhesion in a rat abrasion model. Thus, this agent may be valuable to prevent postoperative adhesion. Keywords: Abdominal; adhesion; cordycepin, experimental; rat; study.

INTRODUCTION Postoperative adhesion is a major complication observed after abdominopelvic surgery. Adhesion may cause infertility, Address for correspondence: Serkan Arslan, M.D. Dicle Üniversitesi Tıp Fakültesi, Çocuk Cerrahi Anabilim Dalı, Diyarbakır, Turkey Tel: +90 412 - 248 80 01 E-mail: drserkanarslan@hotmail.com Submitted: 01.05.2016 Accepted: 08.11.2016

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abdominal or pelvic pain, or obstruction.[1,2] Recently, new surgical techniques, mucosal barriers, and many therapeutic agents, including progesterone, curcumin, methylene blue, vitamin E, surfactants, and hyperbaric oxygen, have been developed in efforts to prevent adhesion, but the work continues. [1,3–6] Cordycepin, an adenosine analogue initially isolated in China in 1964, has been demonstrated to have a variety of biological functions, and is used to treat various medical conditions. Cordycepin has fibrinolytic, anti-apoptotic, antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, nephroprotective, and hepatoprotective effects. It has been used as an herbal tonic in traditional Chinese medicine.[7–9] Adhesion is an important problem for surgeons and has been the subject of many experimental and clinical studies using various parameters. Malondialdehyde (MDA) is a by-product 273

Arslan et al. Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model

Table 1. Grading of adhesion in rats according to the criteria of Nair et al.[10] Grade 0

Complete absence of adhesion

Insubstantial adhesion

Single band of adhesions between the viscera or from 1 viscus to the abdominal wall

Insubstantial adhesion

Two bands, either between the viscera or from the viscera to the abdominal wall

Substantial adhesion

More than 2 bands between the viscera or from the viscera to the abdominal wall, or whole of

intestines forming a mass, without being adherent to the abdominal wall

Substantial adhesion

The viscera directly adherent to the abdominal wall, regardless of number or extent of adhesive bands

Substantial adhesion

formed when oxygen radicals produced by cells break down lipid-containing structures, such as plasma and cell membranes, in the inflammatory response.[10,11,12]

sence of adhesion was confirmed by laparotomy. The abdominal wall was closed using a running suture (3/0 vicryl and 3/0 atraumatic silk).

Tissue damage is used to assess the severity of inflammation and adhesion. Another parameter used to evaluate adhesion is hydroxyproline (OH-p), a hydroxylated derivative of the amino acid proline, which is abundant in collagen. OH-p is useful for assessing adhesion and wound healing.[11]

Adhesion group. A 3-cm midline incision was created in the anterior abdominal wall under sterile conditions. The cecum was removed from the abdomen and scraped with a dry gauze bandage until petechial hemorrhagic foci developed. Standard abrasion model was used.[13,14] The abdominal wall was closed with a continuous suture (3/0 vicryl) and the skin was closed using a 3/0 silk suture.

The aim of the present study was to investigate whether cordycepin would prevent adhesion formation in a rat model.

MATERIALS AND METHODS This study was conducted in the experimental animal and research laboratory of the Faculty of Medicine of Dicle University. Thirty female Wistar Albino rats weighing 220 to 260 g each were used. They received standard food and water ad libitum, and were housed with a 12-hour light/dark cycle for 1 week prior to commencement of the study. Twelve hours prior to administration of anesthesia, food was restricted but water was not. Each rat was anesthetized via intramuscular injection of 5 mg/kg xylazine (Rompun; Bayer AG, Leverkusen, Germany) and 50 mg/kg ketamine hydrochloride (Ketalar; Pfizer, Inc., NY, NY, USA). The anesthetized rats were placed in the supine position. The anterior abdominal wall was shaved and antisepsis was performed using povidone-iodine. The rats were randomly assigned to 3 groups (control, adhesion, and cordycepin groups; 10 rats per group). Control group. A 3-cm midline incision was created in the anterior abdominal wall under sterile conditions and the ab-

Cordycepin group. The procedures described above for the adhesion group were repeated and 10 mg/kg cordycepin (product number C 3394; Sigma-Aldrich Corp., St. Louis, MO, USA) single dose diluted with 0.9% sodium chloride to 1 mL was administered intraperitoneally.[15,16] After 15 days, all animals were humanely sacrificed via cardiac blood withdrawal under anesthesia. Next, a U-shaped incision was created in each abdomen. The abdominal walls were retracted upward to afford maximal field of vision. Adhesion was quantitatively assessed using the classification of Nair et al.[17] (Table 1). The cecum and adherent abdominal wall were then sent for histopathological evaluation and measurement of tissue hydroxyproline level. All tissues were fixed in 10% (v/v) buffered formalin, embedded, processed, and sectioned using conventional laboratory methods. The tissue sections were stained with hematoxylin-eosin and examined under a light microscope.[11] The histopathological evaluations were performed by 2 pathologists blinded to the treatment using ZĂźhlke method (Table 2).[18]

Table 2. Histological classification of adhesion according to ZĂźhlke et al.[11] Grade

274

Loose connective tissue, cell-rich, old and new fibrin, fine reticulin fibers

Connective tissue with cells and capillaries, few collagen fibers

Connective tissue firmer, fewer cells, more vessels, few elastic and smooth muscle fibers

Old firm granulation tissue, cell-poor, serosal layers hardly distinguishable

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Arslan et al. Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model

(a)

(b)

(c)

(d)

Figure 1. (a) Single band of adhesion between the viscera or from one viscus to the abdominal wall. (b) Two bands, either between the viscera or from the viscera to the abdominal wall. (c) More than 2 bands between the viscera or from the viscera to the abdominal wall, or whole of intestines forming a mass, without being adherent to the abdominal wall. (d) The viscera directly adherent to the abdominal wall, regardless of number or extent of adhesive bands.

Biochemical Evaluation

Statistical Analysis

MDA level was measured spectrophotometrically as previously described.[12] A Shimadzu UV-1201 spectrophotometer (Shimadzu Corp., Kyoto, Japan) was used to measure color change upon reaction of thiobarbituric acid (TBA) with MDA. TBA concentration (µmoles/L) was calculated based on absorbance coefficient of the MDA-TBA complex. A dimethyl acetal-TBA complex served as a standard.[19]

All data were analyzed using SPSS for Windows, Version 15.0 (SPSS Inc., Chicago, IL, USA). Kruskal-Wallis test was used to compare multiple independent samples. When a significant difference was evident, Mann-Whitney U test was employed for paired in-group comparisons. P value ≤0.05 was considered statistically significant.

Serum level of OH-p (catalog no: 201-11-0512; Shanghai Sunred Biological Technology Co., Shanghai, China) was measured using an enzyme-linked immunosorbent assay kit according to the manufacturer’s instructions. Briefly, samples were transferred to pre-coated wells, and then biotin-labeled antibodies were added. Initially, streptavidin-horseradish peroxidase was added to the wells. After incubation, the wells were washed to remove unbound antibodies. Next, chromogen solutions A and B were added and absorbance at 450 nm was measured. All data were recorded as previously described. In short, tissue particles (0.12–0.25 g) were washed several times with physiological saline, dried on blotting paper, placed into Eppendorf tubes, and stored at -85°C. After all sampling procedures had been concluded, tissue samples were removed from the freezer and homogenized using an automated tissue homogenizer. The MDA and OH-p levels in tissue particles were measured and normalized to the total protein level of homogenized tissue.

(a)

(b)

RESULTS The levels of OH-p and MDA in blood and tissue were higher in the adhesion group than in the control group. Interestingly, the MDA level was significantly lower (blood: p<0.05; tissue: p<0.01) in the cordycepin group than in the adhesion group, whereas only tissue OH-p was significantly lower in the cordycepin group compared with the adhesion group (p<0.05). Macroscopic analysis revealed significantly less adhesion in the cordycepin group than in the adhesion group in terms of grade assigned using the Nair system (p<0.01) (Fig. 1). Furthermore, significant histopathological improvement was also evident in the cordycepin group compared with the adhesion group in terms of Zühlke histopathological grading (p<0.05) (Figs. 2, 3). One rat in both the cordycepin group and the adhesion group died immediately after surgery, probably due to an anesthetic complication. The detailed findings are provided in Table 3.

(c)

(d)

Figure 2. (a) The control group was nonspecific. Hematoxylin-eosin (HE); x100. (b) Loose connective tissue (arrow), rich in cells, rare vascular formations. HE; x100. (c) Loose connective tissue, including cells and capillaries, rare collagen fibers (arrow). HE; x100. (d) Dense connective tissue, decreased inflammatory cells, significantly increased vascular formations (thin arrow), rare smooth muscle fibers. HE; x100.

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Arslan et al. Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model

Group Adhesion Cordycepin

4.00

Group Adhesion Cordycepin

3.00

Histopathology

Macroscopy

3.00

2.00

1.00 1.00

0.00

A1A2 A3 A4A5 A6 A7 A8A9 C1C2C3 C4C5C6 C7C8C9

Subject

A1 A2 A3 A4 A5A6 A7 A8 A9 C1C2C3C4C5C6C7C8C9

Subject

Figure 3. Macroscopic and histopathological evaluation results of rats in adhesion and cordycepin group.

DISCUSSION Adhesion is the most common complication to develop after an intra-abdominal procedure.[5] Adhesion increases vascular permeability and triggers fibrin release.[20] Adhesion formation is stimulated by plasminogen and increased level of inflammatory cytokines in postoperative tissue. Inadequate fibrinolytic capacity of tissue facilitates adhesion formation. [3] Inflammation develops early after surgery, and fibroblasts appear later. Then, collagen synthesis increases. Although several promising methods are used to prevent adhesion, no standard treatment is yet available.[2] Therefore, several different agents remain under evaluation.[20] Cordycepin was first isolated in 1950. It was made in vivo, and later in in vitro studies.[21] It is known to suppress inflammation, reduce inflammatory cytokine level, and inhibit fibrin release.[8,9] Recently, use of cordycepin has been examined in experimental studies of diabetes mellitus, osteoporosis, and hepatocellular carcinoma, but not adhesion.[22–26] Cordycepin metabolites appear in the blood and liver 2 hours after it is administered. To overcome the problem of rapid elimination, a large dose

must be administered.[26,27] Experimental studies have used intravenous cordycepin doses of 5, 10, 20 and 40 mg/kg/day. [15,16] We chose a single dose of 10 mg/kg, but further studies on dosage are required. Various experimental models of adhesion have been reported, including abrasion, local peritoneal excision, ischemic injury, placement of a foreign body in the peritoneal cavity, thermal injury, deliberate bacterial contamination, and others.[28–33] In this study, the standard abrasion model was adopted, since it simulates mechanical trauma caused by laparotomy, which is the most common cause of adhesion. Adhesion was created in the standard manner of abrasion until petechial hemorrhage occurred. To assess the development of adhesion, MDA and OH-p levels, known biochemical markers of adhesion, were measured. [10–12] The OH-p level reflects the level of collagen, and is recognized to be a good indicator of wound healing. Ozoğul et al.[10] tested aprotinin in an adhesion model and found that

Table 3. Detailed analysis of all groups

Group 1 (Control, n=10)

Group 2 (Adhesion, n=9)

Group 3 (Cordycepin, n=9)

Mean±SD, Range (Min-Max)

Mean±SD Range (Min-Max)

848±218 (616–1261)

928±164 (630–1092)

853±131 (667–1085)

>0.05

5.6±4 (4–18)

18±8 (8–28)

7.2±5 (4–20)

<0.05

Tissue OH-p (Ng/g protein)

629±375 (109–1207)

1141±485 (351–1955)

665±233 (250–972)

<0.05

Tissue MDA (µM/g protein)

14±7 (7–27)

23±3 (19–27)

18±4 (9–21)

<0.01

Blood OH-p (ng/mL) Blood MDA (µM)

p(2,3)

Macroscopy

3±0.7 (2–4)

1±0.6 (0–2)

<0.01

Histopathology

2.4±0.4 (2–3)

1.4±0.5 (1–2)

<0.05

MDA: Malondialdhyde; OH-p: Hydroxyproline; SD: Standard deviation; Min: Minimum; Max: Maximum.

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the OH-p level fell compared with the control group. Baykal et al.[11] tested polyglycolic acid in an adhesion model and found a significant association between adhesional grade and OH-p level. Okur et al.[12] tested an extract of Ecballium elaterium in an adhesion model and found that the OH-p level was higher in the adhesion group. In this study, the OH-p level in tissue and blood decreased in the cordycepin group compared with the adhesion group, but the difference was significant only in tissue (p<0.05). We attributed the increase in OH-p level observed in the adhesion group to collagen accumulation. OH-p is an essential amino acid found in all types of collagen in the body. Ninety percent of OH-p is metabolized in the liver and 10% is metabolized in the kidneys. The OH-p level in the blood changes for various reasons.[34] In this study, the tissue OH-p level was significantly lower in the cordycepin group compared with the adhesion group, while the decline seen in the blood was not significant, perhaps because OH-p in the blood takes 15 days to be metabolized. MDA, an end-product of lipid peroxidation, is a marker of oxidative stress. Tissue damage can elevate MDA level.[35] Physiological changes associated with the development of adhesion can increase oxidative stress. Ten Raa et al.[36] found a positive correlation between severity of adhesion and oxidative grade. Furthermore, Ara et al.[37] demonstrated that MDA level was elevated in a peritoneal adhesion group and reduced in a test group. Similarly, Özler et al.[38] found that MDA level decreased in a treatment group but increased in an untreated adhesion group. We found that MDA levels in both blood and tissue were significantly lower in the cordycepin group than in the adhesion group (p<0.05, p<0.01, respectively). Various scoring systems are used to macroscopically evaluate adhesion.[17] We found that the cordycepin group had significantly less adhesion formation than the adhesion group (p<0.01). Histopathological evaluation revealed a significant decrease in the number of collagen fibers in the cordycepin group compared to the adhesion group (p<0.05). This study had several limitations, including the dosage of cordycepin, time interval, administration method, and bioavailability. Therefore, further studies should be conducted in small or large animal models before proceeding to clinical studies in humans.

Conclusions We found that cordycepin effectively reduced adhesion in a rat abrasion model. Thus, this agent may be valuable to prevent postoperative adhesion. However, further studies on its clinical indications, safety, and dosage are required. Ethical approval The article was approved by the animal ethics committee of the Medical Faculty of Dicle University. Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Sources of support This study was supported by the Scientific Research and Project Coordinator (DUBAP, 14-TF-44) of Dicle University. Laboratory Research was performed at the experimental animal laboratory, Dicle University, Diyarbakır, Turkey. Conflict of interest None declared.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Cordycepin’in sıçan modelinde karıniçi adezyonun ameliyat sonrası önleyici etkisi: Deneysel çalışma Dr. Serkan Arslan,1 Dr. Hikmet Zeytun,1 Dr. Erol Basuguy,1 Dr. İbrahim İbiloğlu,2 Dr. İbrahim Uygun,1 Dr. Ahmet Yılmaz,3 Dr. İlhan Tan,4 Dr. Gülten Toprak5 Dicle Üniversitesi Tıp Fakültesi, Çocuk Cerrahi Anabilim Dalı, Diyarbakır Dicle Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Diyarbakır Dicle Üniversitesi Tıp Fakültesi, Aile Hekimliği Anabilim Dalı, Diyarbakır 4 Dicle Üniversitesi Tıp Fakültesi, Pediatri Anabilim Dalı, Diyarbakır 5 Dicle Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Diyarbakır 1 2 3

AMAÇ: Cordycepin’in sıçan modelinde adezyonu önleyip önlemediğini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Her biri 10’ar adet olmak üzere sıçanlar rastgele üç gruba ayrıldı. Kontrol grubu: Laparotomi ile adezyonun olmadığını doğruladık. Adezyon grubu: Çekum abdomenden çıkarıldı ve kuru spanç ile peteşial hemoraji odakları oluşana kadar scraping yapıldı. Cordycepin grubu: Aynı cerrahi prosedür adezyon grubunda tanımlandığı gibi yapıldı, ancak 10 mg/kg cordycepin intraperitoneal olarak uygulandı. On beş gün sonra sıçanlar anestezi altında kardiyak kan çekme yoluyla sakrifiye edildi. Daha sonra sıçanlar morfolojik ve histopatolojik olarak analiz edildi ve hydroxyproline (OH-p) ve malondialdehyde (MDA) düzeyleri ölçüldü. BULGULAR: Makroskobik olarak adezyonun Cordycepin grubunda adezyon grubuna göre anlamlı derecede azaldığı görüldü (p<0.01). Bununla birlikte histopatolojik düzelmede Cordycepin grubunda adezyon grubuna göre anlamlı derecede düzelme görüldü (p<0.05). Kan ve doku OH-p ve MDA düzeyleri kontrol grubuna göre adezyon grubunda daha yüksekti. Bu değerler Cordycepin grubunda adezyon grubuna göre daha düşüktü. Malondialdehit seviyesi Cordycepin grubunda adezyon grubuna göre istatistiksel olarak anlamlı derecede düşüktü (kan p<0.05, doku p<0.01). Buna karşılık yalnızca doku OH-p düzeyi adezyon grubuna göre Cordycepin grubunda istatistiksel olarak anlamlı derecede düşüktü (p<0.05). Adezyon ve Cordycepin grubunda birer sıçan ameliyat sonrası kaybedildi. TARTIŞMA: Cordycepin sıçan abrazyon modelinde adezyonu etkili olarak azalttığını tespit ettik. Bu yüzden bu ajan ameliyat sonrası adezyonu önlemek için değerli olabilir. Anahtar sözcükler: Abdominal; adezyon; Cordycepin; çalışma; deneysel; sıçan. Ulus Travma Acil Cerrahi Derg 2017;23(4):273–278

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doi: 10.5505/tjtes.2016.48979

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EXPERIMENTAL STUDY

Protective effects of dexmedetomidine and remote ischemic preconditioning on renal ischemia reperfusion injury in rats Cansu Balcı, M.D.,1 Mert Akan, M.D.,2 Nilay Boztaş, M.D.,3 Sevda Özkardeşler, M.D.,3 Bekir Uğur Ergür, M.D.,4 Mustafa Ensari Güneli, M.D.,5 Belgin Ünal, M.D.6 1

Department of Anesthesiology and Reanimation, Çanakkale State Hospital, Çanakkale-Turkey

Department of Anesthesiology and Reanimation, Kent Hospital, İzmir-Turkey

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

Department of Histology and Embryology, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

Department of Laboratory Animal Science, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

Department of Public Health, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: The aim of this study was to evaluate the effects of remote ischemic preconditioning (RIPC) and dexmedetomidine as pharmacological conditioning in a rat renal ischemia/reperfusion (IR) injury model. METHODS: Total of 28 male Wistar Albino rats weighing 250 to 300 g were divided into 4 equal groups. Group I (Sham; n=7): Laparotomy and renal pedicle dissection were performed, and the rats were observed under anesthesia without any intervention. Group II (IR; n=7): Following laparotomy and 45 minutes of left renal pedicle occlusion, 4 hours of reperfusion was performed. Group III (IR+D; n=7): Following laparotomy and ischemia, dexmedetomidine was administrated intraperitoneally (100 μg/kg) at fifth minute of reperfusion. Group IV (RIPC+IR; n=7): Under anesthesia, 3 cycles of ischemic preconditioning were applied to the left hind leg, and after 5 minutes, renal IR was performed. All rats were sacrificed after the left kidney was processed for conventional histomorphology. RESULTS: Total histomorphological renal injury score was significantly lower in the Sham group compared with the other groups (p<0.01). Total renal injury score of IR group was significantly higher than IR+D and RIPC+IR groups (p<0.01). There was no significant difference in the total renal injury score between the dexmedetomidine and RIPC groups (p=0.89). CONCLUSION: In the present study, it was demonstrated histomorphologically that both dexmedetomidine and RIPC decreased renal IR injury significantly. In addition, no significant difference was found between dexmedetomidine and RIPC groups. Keywords: Dexmedetomidine; ischemia reperfusion injury; kidney; remote ischemic preconditioning.

INTRODUCTION Ischemia is defined as the partial or total restriction of blood flow to a certain tissue or organ for a limited period of time, and reperfusion is the restoration of blood flow. Restoration of blood flow can be even more harmful to tissues than the Address for correspondence: Cansu Balcı, M.D. 374 Sokak, Görgün Sitesi, No: 7, İris Apt., D: 1, Salihli, Manisa, Turkey Tel: +90 236 - 713 15 00 E-mail: cansubal35@hotmail.com Submitted: 02.03.2016 Accepted: 04.10.2016

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ischemic injury.[1] Severity of ischemia/reperfusion (IR) injury depends on ischemic duration and adequacy of collateral circulation. IR injury is commonly encountered in various clinical conditions, such as ischemic cerebrovascular accident, myocardial infarction, cardiopulmonary resuscitation, and tourniquet application.[2] During the ischemic period, related tissue synthesizes excessive amounts of toxic, free oxygen radicals. Free oxygen radicals are known to play a critical role in the physiopathology of IR damage.[3,4] During reperfusion, free oxygen radicals cause endothelial damage, elevated microvascular permeability, and tissue edema.[5,6] Furthermore, activated adhesion molecules and cytokines may trigger systemic inflammatory response syndrome.[7] These toxic substances may in turn lead to multiple organ failure, which may require long-term intensive care due to damage in remote organs, such as the lungs, kidneys, and heart.[8,9] 279

Balcı et al. Protective effects of dexmedetomidine and remote ischemic preconditioning on renal ischemia reperfusion injury in rats

Various methods have been developed to prevent such damage. Ischemic preconditioning (IPC) and pharmacological conditioning are the most commonly used methods. IPC has been defined as a process that increases tissue resistance to long-term ischemia via reperfusion periods following short ischemic episodes.[10] It is categorized in 2 groups: direct and remote IPC (RIPC). In direct IPC, the organ is subjected to short-term IR episodes before long-term ischemia. In IPC, ischemia is maintained in remote organ other than the organ to be protected.[11] Another method used to prevent or reduce IR damage is pharmacological pre- and postconditioning. Dexmedetomidine is an alpha2-adrenergic receptor agonist and wide-spectrum sedative and analgesic drug commonly used in intensive care settings.[12] Trials using ischemic and inflammatory response models have demonstrated that dexmedetomidine has an anti-inflammatory effect with protective properties against IR injury.[13] In this study, the aim was to compare the effects of pharmacological postconditioning with dexmedetomidine and IPC in an experimental rat model of renal IR injury.

MATERIALS AND METHODS The present study was performed at the experimental animal laboratory of 9 Eylül University. Experimental protocols and animal care methods used were approved by the institutional experimental animal research committee. Twenty-eight adult male Wistar Albino rats weighing 250 to 300 g were used in this study. The rats were housed with 12hour light/dark cycle at room temperature under 40% to 60% relative humidity, fed standard pellet diet, and provided with water. Access to food and water was unlimited. Anesthesia was achieved with 50 mg/kg intraperitoneal (ip) ketamine and 10 mg/kg xylazine hydrochloride. The animals were randomly separated into 4 groups of 7 rats. Group I (Sham; n=7): Abdominal dissection was performed at 65th minute of anesthesia protocol, left renal pedicle was dissected, and the rats were kept under anesthesia for an additional 285 minutes without any further intervention. Group II (IR; n=7): Abdominal dissection was performed at 65th minute of anesthesia protocol, left kidney was subjected to total ischemia for 45 minutes followed by reperfusion for 4 hours. Group III (IR+D; n=7): Abdominal dissection was performed at 65th minute of anesthesia protocol, left kidney was subjected to IR (45 minutes ischemia + 4 hours reperfusion), and 100 µg/kg ip dexmedetomidine (Precedex 100 mcg/2 mL vial; Abbott Laboratories, Lake Bluff, IL, USA) was injected 5 minutes after reperfusion. Group IV (RIPC+IR; n=7): Following abdomen dissection, 3 cycles of 10 minutes ischemia + 10 minutes reperfusion 280

combination was applied to left hind leg. Five minutes later, procedure described in Group II was performed. Exposing left renal pedicle in Group I, and initiating ischemia at the 65th minute of anesthesia in Groups II and III, was intended to synchronize all groups to preconditioning time of Group IV and to standardize the beginning of the procedures. Tissue samples were obtained at the end of reperfusion.

Experimental Study Design Following anesthesia protocol, each rat was fixed on the operating table in the supine position and the abdomen was dissected with median line incision. The left kidney was exposed, and the renal pedicle was dissected. In order to protect the rats from hypothermia, operating table was warmed with a heat lamp throughout the procedure. Body temperature was maintained at 37°C to 37.5°C. Saline solution was delivered subcutaneously at 3 mL/kg/h dose to prevent dehydration. The abdomen was kept closed during IR.

Renal Ischemia Reperfusion Model Left renal ischemia was induced by clamping the renal pedicle with atraumatic microvascular clamp. Adequate occlusion was verified by the absence of pulsation in the renal pedicle and paleness of the kidney. After completing ischemia duration, microvascular clamp was removed to permit reperfusion.

Remote Ischemic Preconditioning Model Elastic bandage (1 cm width x 30 cm length) was rolled tightly around the left hind leg 3 times. Three cycles of 10 minutes of ischemia + 10 minutes of reperfusion were applied. Blockage of blood flow was verified with a laser flowmeter. In all groups, the left kidney was removed for histomorphological examination at the end of the total study period and the rats were sacrificed via exsanguination (cardiac puncture). Tissue samples were fixed in 10% buffered formaldehyde and renal damage was assessed histologically.

Histomorphological Evaluation of Renal Tissue Kidney samples were examined in blinded fashion in the histology-embryology department of the institution.

Tissue Examination Protocol Kidney specimens were stained with hematoxylin-eosin for analysis of histomorphological properties and Masson’s trichrome for connective tissue examination.

Histomorphological Evaluation of Renal Tissue Sections were stained and examined under a light microscope. Images obtained from the samples were transferred to a computer using a high-resolution camera and evaluated thoroughly with a digital image analysis program. Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Balcı et al. Protective effects of dexmedetomidine and remote ischemic preconditioning on renal ischemia reperfusion injury in rats

Renal sections with ischemic reperfusion were examined under a light microscope to evaluate structural changes in the proximal tubules (tubular atrophy, brush border loss, vacuolization, tubular dilatation, and cast formation), mononuclear cell infiltration, erythrocyte extravasation, interstitial structural changes, renal corpuscular morphology, and necrotic and apoptotic cells. Images obtained from the sections were scored semiquantitatively in terms of tubulointerstitial damage. Scoring was as follows: 0=none, 1=0–25%, 2=26–45%, 3=46–75%, 4=76–100%.

Exclusion Criteria Rats in need of resuscitation were to be excluded from the study.

Statistical Analysis SPSS for Windows, Version 15.0 (SPSS Inc., Chicago, IL, USA) software was used for statistical analyses. Data analysis was performed with Kruskal-Wallis test. Paired comparisons were evaluated with Mann-Whitney U test. Data were expressed as mean±SD. P value <0.05 was accepted as statistically significant.

RESULTS Total of 28 rats were included in the study and all of the rats completed the study. Histomorphological damage scores are provided in Table 1, and comparative significance of the scores can be seen in Table 2.

Table 1. Histomorphological damage scores of the groups

Proximal tubule damage scores

Mononuclear cell infiltration

Erythrocyte extravasation and capillary dilatation

Histomorphological damage total score

Mean±SD Mean±SD

Mean±SD

Group I (n=7) (Sham)

0.00±0.00

0.14±0.37

0.28±0.48

0.42±0.78

Group II (n=7) (IR)

2.28±0.48

1.57±0.53

2.42±0.78

6.2±1.25

Group III (n=7) (IR+D)

1.28±0.48

1.14±0.37

1.42±0.53

3.85±0.89

Group IV (n=7) (IR+RIPC)

1.42±0.53

1.14±0.37

1.42±0.53

4.00±1.15

pa <0.001* 0.001* 0.001* <0.001* IR: Ischemia reperfusion; D: Dexmedetomidine; RIPC: Remote ischemic preconditioning; SD: Standard deviation.

Table 2. Comparison of histomorphological damage scores with regard to significance

Ischemia reperfusion

Ischemia reperfusion+ dexmedetomidine

Ischemia reperfusion+ remote ischemic preconditioning

Proximal tubule damage scores Sham

0.001* 0.001* 0.001*

Ischemia reperfusion

0.006* 0.015*

Ischemia reperfusion+dexmedetomidine

0.59

Mononuclear cell infiltratio Sham

0.002* 0.002* 0.002*

Ischemia reperfusion

Ischemia reperfusion+dexmedetomidine

0.10

0.10 1.00

Erythrocyte extravasation and capillary dilatation Sham

0.002* 0.005* 0.005*

Ischemia reperfusion

0.02* 0.02*

Ischemia reperfusion+dexmedetomidine

1.00

Histomorphological damage total score Sham

0.001* 0.001* 0.001*

Ischemia reperfusion

0.005* 0.009*

Ischemia reperfusion+dexmedetomidine

0.89

p<0.05: Intergroup significant difference. aMann-Whitney U test.

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Mononuclear Cell Infiltration The Sham group demonstrated a significantly lower histomorphological damage score compared with the IR, IR+D, and RIPC+IR groups (p=0.002, p=0.002, p=0.002, respectively). No significant difference was found between the IR, IR+D and RIPC+IR groups (p=0.1, p=0.1, respectively) (Fig. 2).

Erythrocyte Extravasation and Capillary Dilatation The Sham group demonstrated a significantly lower histomorphological damage score compared with the IR, IR+D, and RIPC+IR groups (p=0.002, p=0.005, p=0.005, respectively). Comparison between the IR, IR+D, and RIPC+IR groups revealed significant differences (p=0.02, p=0.02, respectively). The IR group displayed a significantly higher damage score compared with the IR+D and RIPC+IR groups, whereas no significant difference was determined between the IR+D and RIPC+IR groups (p=1.00) (Fig. 3).

Sham group samples had normal histomorphological proper-

Mononüclear cell infiltration

The Sham group demonstrated a significantly lower histomorphological damage score compared with IR, IR+D, and RIPC+IR groups (p=0.001, p=0.001, p=0.001, respectively). Comparison between IR, IR+D, and RIPC+IR groups revealed significant differences (p=0.006, p=0.015, respectively). IR group displayed significantly higher damage score compared with the IR+D and RIPC+IR groups, whereas no significant difference was determined between the IR+D and RIPC+IR groups (p=0.59) (Fig. 1).

score compared with the IR+D and RIPC+IR groups, whereas no significant difference was determined between the IR+D and RIPC+IR groups (p=0.89) (Fig. 4).

4 3 2 * 1 0

Sham

The Sham group demonstrated a significantly lower histomorphological damage score compared with the IR, IR+D, and RIPC+IR groups (p=0.001, p=0.001, p=0.001, respectively). Comparison between the IR, IR+D, and RIPC+IR groups revealed significant differences (p=0.005, p=0.009, respectively). The IR group displayed a significantly higher damage

3 *

** #

Sham

D+IR

*** †

RIPC+IR

Total histomorphologic damage score

Structural changes in the proximal tubule

RIPC+IR

3 *

2 1

Sham

** #

*** †

D+IR

RIPC+IR

Figure 1. Renal histomorphological evaluation with regard to damage scores in the proximal tubules. *Comparison of IR and Sham groups (p=0.001). **Comparison of IR+D and Sham groups (p=0.001). ***Comparison of IR+RIPC and Sham groups (p=0.001). # Comparison of IR+D and IR groups (p=0.006). †Comparison of IR+RIPC and IR groups (p=0.015). D: Dexmedetomidine; IR: Ischemia/reperfusion; RIPC: Remote ischemic preconditioning.

282

D+IR

Figure 3. Renal histomorphological evaluation with regard to erythrocyte extravasation and capillary dilatation. *Comparison of IR and Sham groups (p=0.002). **Comparison of IR+D and Sham groups (p=0.005). ***Comparison of RIPC+IR and Sham groups (p=0.005). #Comparison of IR+D and IR groups (p=0.02). †Comparison of IR+RIPC and IR groups (p=0.02). D: Dexmedetomidine; IR: Ischemia/reperfusion; RIPC: Remote ischemic preconditioning.

***

Total Histomorphological Damage Score

Figure 2. Renal histomorphological evaluation of with regard to mononuclear cell infiltration. *Comparison of IR and Sham groups (p=0.002). **Comparison of IR+D and Sham groups (p=0.002). ***Comparison of IR+RIPC and Sham groups (p=0.002). D: Dexmedetomidine; IR: Ischemia/reperfusion; RIPC: Remote ischemic preconditioning.

Erythrocyte extravasation and capillary dilatation

Renal Histomorphological Damage Score Structural Changes in the Proximal Tubules

** #

*** †

3 2 1 0

Sham

D+IR

RIPC+IR

Figure 4. Renal histomorphological evaluation with regard to total histomorphological damage score. *Comparison of IR and Sham groups (p=0.001). **Comparison of IR+D and Sham groups (p=0.001). ***Comparison of RIPC+IR and Sham groups (p=0.001). # Comparison of IR+D and IR groups (p=0.005). †Comparison of IR+RIPC and IR groups (p=0.009). D: Dexmedetomidine; IR: Ischemia/reperfusion; RIPC: Remote ischemic preconditioning.

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Balcı et al. Protective effects of dexmedetomidine and remote ischemic preconditioning on renal ischemia reperfusion injury in rats

ties and none of the sections in this group exhibited cell infiltration or brush border loss (Figs. 5a, b). Tubular atrophy, tubular dilatation, mononuclear cell infiltration in the peritubular area, vacuolization, and brush border loss in the proximal tubules were observed in the IR group. In some tubules, proteinaceous material deposits and cast formation was noted, and cellular debris in the tubule lumen was found. Some cortical areas displayed dilated vessels and erythrocyte extravasation (Figs. 6a-d).

(a)

Compared with the IR group, the IR+D group demonstrated less tubular atrophy, tubular dilatation, and vacuolization, as well as fewer proteinaceous material deposits and less cast formation in some tubules, cellular debris, and brush border loss in the tubule lumen. There was less mononuclear cell infiltration in the peritubular area and erythrocyte extravasation in the IR+D group than in the IR group (Figs. 7a-d). Compared with the IR group, the RIPC+IR group demonstrated less degeneration in tubule cells, cortical erythrocyte

(b)

Figure 5. (a, b) Sections from the Sham group. D: Distal tubule; G: Glomerulus; P: Proximal tubule.

(a)

(b)

(c)

(d)

Figure 6. (a, b) Sections from the IR group. () Accumulation of proteinaceous material in tubules. (*) Proximal tubule epithelial cells in the lumen. (c) Section from the IR group. () Mononuclear cell infiltration. (*) Erythrocyte extravasation. (d) Section from the IR group. () Mononuclear cell infiltration. D: Distal tubule; G: Glomerulus; IR: Ischemia/ reperfusion; P: Proximal tubule.

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extravasation, and mononuclear cell infiltration in the peritubular area. The RIPC+IR group had less brush border loss in the tubules, tubular atrophy, tubular dilatation, vacuolization, proteinaceous material deposits, and cellular debris in the tubule lumen (Figs. 8a, b).

Although comparison between the IR+D and RIPC+IR groups revealed no significant difference, the IR+D group had histomorphologically less brush border loss, tubular atrophy, vacuolization, proteinacious deposits, cast formation, and cellular debris in the tubule lumen.

(a)

(b)

(c)

(d)

Figure 7. (a, b) Sections from the IR+dexmedetomidine group. () Mononuclear cell infiltration. (*) Erythrocyte extravasation. (c, d) Sections from the IR+dexmedetomidine group. () Accumulation of proteinaceous material in tubules. Proximal tubule epithelial cells in the lumen. D: Distal tubule; G: Glomerulus; IR: Ischemia/reperfusion; P: Proximal tubule.

(a)

(b)

Figure 8. (a, b) Sections from the IR+RIPC group. D: Distal tubule; G: Glomerulus; IR: Ischemia/reperfusion; P: Proximal tubule; RIPC: Remote ischemic preconditioning. () Erythrocyte extravasation. (*) Mononuclear cell infiltration. (é) Reduced accumulation of proteinaceous material.

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DISCUSSION In this experimental study, the protective effects of RIPC and dexmedetomidine were compared using a rat renal IR model, and the results demonstrated that both methods were protective against IR injury. The renal histomorphological total damage score was lower in the IR+D group than in the RIPC+IR group. In the present study, as in the studies of Williams et al.[14] and Cochrane et al.,[15] ischemic duration of 45 minutes and reperfusion duration of 4 hours, which allows for observation of earliest renal damage, was performed. The fact that histomorphological damage scores were significantly higher in the IR group than in the Sham group indicated that adequate renal IR damage can be obtained using this model. Studies illustrating the impact of RIPC in reducing IR damage have presented a noninvasive method to prevent IR damage. Saita et al.[16] noted that the best IPC method for preventing IR damage in skeletal muscle is to apply 3 successive cycles of 10 minutes ischemia + 10 minutes reperfusion. Şahin et al.[9] found that 3 cycles of 10 minutes RIPC applied as a tourniquet on the hind leg significantly reduced liver IR damage compared with direct IPC. In the present study, we elected to use this RIPC method: 3 cycles of 10 minutes ischemia followed by 10 minutes reperfusion via noninvasive tourniquet. When compared with the RIPC group, significantly higher histomorphological total damage scores were observed in the IR group. This result suggests that RIPC may have a protective effect against renal IR damage. In some experimental studies, pharmacological agents have been used to prevent IR injury. Those drugs are thought to have some effects on the mechanism of IR damage. In pharmacological conditioning method, drugs can be used in prophylaxis (preconditioning) or in treatment (postconditioning).[17–19] Dexmedetomidine is a pharmacological agent that has been used in many experimental studies investigating prevention of IR damage; however, no study related to comparison of effects of dexmedetomidine and RIPC on renal IR injury was found in our PubMed and Excerpta Medica Database search. We chose dexmedetomidine is because it is a safe drug that has been commonly used in anesthesia and critical care practice for many years. Dexmedetomidine could potentially be used in clinical practice to prevent renal IR injury. Dexmedetomidine has been reported to have protective effects not only against renal ischemia, but also cardiac IR damage and incomplete frontal brain ischemia in rats.[20–23] The exact mechanism of the protective effects of dexmedetomidine against IR damage is not yet known, but in renal Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

tissue, for example, it is believed to increase renal blood flow and glomerular filtration by reducing noradrenaline release. [24] Gu et al.[25] reported that renal IR damage can be reduced with dexmedetomidine by suppressing the inflammatory cascade via decreasing renal cell death, high mobility group box 1 protein release, and toll-like receptor 4. The histopathological impact of this agent on renal IR was first noted by Kocoglu et al. They found that administration of 100 µg/kg ip dose of dexmedetomidine at the beginning of reperfusion therapy reduced the histomorphological damage associated with IR. Similarly, we administered 100 µg/kg ip dose of dexmedetomidine 5 minutes after reperfusion. In the present study, the IR group demonstrated significantly higher total damage scores compared with the Sham group. This result indicated appropriate ischemic model. The results of our study demonstrated histomorphologically that both dexmedetomidine and RIPC decreased renal IR injury significantly. The IR+D group displayed a relatively lower histomorphological total damage score (less tubular atrophy, tubular dilatation, vacuolization, brush border loss in the proximal tubule cells, proteinaceous deposits, cast formation, and cellular debris in the tubule lumen) compared with the RIPC+IR group. This fact may suggest that dexmedetomidine may be a better protector against IR with greater efficacy in decreasing renal damage compared with RIPC. In conclusion, both methods are noninvasive and easily applicable without increasing the duration of surgery. Further studies should be conducted in future to evaluate the best dosage and administration period. Conflict of interest: None declared.

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Balcı et al. Protective effects of dexmedetomidine and remote ischemic preconditioning on renal ischemia reperfusion injury in rats parison of the Effects of the Remote and Direct Ischemic Preconditioning in the Liver Ischemia-Reperfusion Injury. Turkiye Klinikleri JMed Sci 2009;29:381–7. 10. Laurikka J, Wu ZK, Iisalo P, Kaukinen L, Honkonen EL, Kaukinen S, Tarkka MR. Regional ischemic preconditioning enhances myocardial performance in off-pump coronary artery bypass grafting. Chest 2002;121:1183–9. 11. Takaoka A, Nakae I, Mitsunami K, Yabe T, Morikawa S, Inubushi T, Kinoshita M. Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of “remote preconditioning”. J Am Coll Cardiol 1999;33:556–64. 12. Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent) 2001;14:13– 21. 13. Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med 2004;32:1322–6. 14. Williams P, Lopez H, Britt D, Chan C, Ezrin A, Hottendorf R. Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods 1997;37:1–7. 15. Cochrane J, Williams BT, Banerjee A, Harken AH, Burke TJ, Cairns CB, et al. Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat. Ren Fail 1999;21:135–45. 16. Saita Y, Yokoyama K, Nakamura K, Itoman M. Effect of ischaemic preconditioning against ischaemia-induced reperfusion injury of skeletal muscle: how many preconditioning cycles are appropriate. JPlast Surg 2002;55:1–5. 17. Kocoglu H, Ozturk H, Ozturk H, Yilmaz F, Gulcu N. Effect of dexme-

detomidine on ischemia-reperfusion injury in rat kidney: a histopathologic study. Ren Fail 2009;31:70–4. 18. Frumento RJ, Logginidou HG, Wahlander S, Wagener G, Playford HR, Sladen RN. Deksmedetomidine infusion is associated with enhanced renal function after thoracic surgery. J Clin Anesth 2006;18:422–6. 19. Villela NR, do Nascimento Júnior P, de Carvalho LR, Teixeira A. Effects of dexmedetomidine on renal system and on vasopressin plasma levels. Experimental study in dogs. Rev Bras Anestesiol 2005;55:429–40. 20. Hoffman WE, Kochs E, Werner C, Thomas C, Albrecht RF. Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole. Anesthesiology 1991;75:328–32. 21. Maier CM, Sun GH, Kunis DM, Giffard RG, Steinberg GK. Neuroprotection by the N-methyl-D-aspartate receptor antagonist CGP 40116: in vivo and in vitro studies. J Neurochem 1995;65:652–9. 22. Kocoglu H, Karaaslan K, Gonca E, Bozdogan O, Gulcu N. Preconditionin effects of dexmedetomidine on myocardial ischemia/reperfusion injury in rats. Curr Ther Res Clin Exp 2008;69:150–8. 23. Engelhard K, Werner C, Eberspächer E, Bachl M, Blobner M, Hildt E, et al. The effect of the alpha 2-agonist dexmedetomidine and the N-methylD-aspartate antagonist S(+)-ketamine on the expression of apoptosisregulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg 2003;96:524–31. 24. Taoda M, Adachi YU, Uchihashi Y, Watanabe K, Satoh T, Vizi ES. Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor. Neurochem Int 2001;38:317–22. 25. Gu J, Sun P, Zhao H, Watts HR, Sanders RD, Terrando N, et al. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Critical Care 2011;15:153.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deksmedetomidin ve uzak iskemik ön koşullamanın sıçanlarda renal iskemi reperfüzyon hasarı üzerine koruyucu etkileri Dr. Cansu Balcı,1 Dr. Mert Akan,2 Dr. Nilay Boztaş,3 Dr. Sevda Özkardeşler,3 Dr. Bekir Uğur Ergür,4 Dr. Mustafa Ensari Güneli,5 Dr. Belgin Ünal6 Çanakkale Devlet Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Çanakkale Kent Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, İzmir Dokuz Eylül Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Bilim Dalı, İzmir 4 Dokuz Eylül Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, İzmir 5 Dokuz Eylül Üniversitesi Tıp Fakültesi, Deney Hayvanları Bilim Dalı, İzmir 6 Dokuz Eylül Üniversitesi Tıp Fakültesi, Halk Sağlığı Anabilim Dalı, İzmir 1 2 3

AMAÇ: Şok, böbrek transplantasyonu, kısmi nefrektomi, kardiyopulmoner baypas, sepsis gibi çeşitli klinik durumlarda ortaya çıkabilen iskemi reperfüzyon (İR) hasarı hastada ciddi organ yetersizliklerine neden olabilmektedir. İskemi reperfüzyon hasarını azaltmak amacıyla kullanılan yöntemlerden bazıları uzak iskemik ön koşullama (UİÖK) ve farmakolojik koşullamadır. Bu çalışmanın amacı; sıçan renal İR modelinde tek taraflı arka ekstremiteye uygulanacak UİÖK ile farmakolojik koşullama olarak deksmedetomidin kullanımının etkilerinin karşılaştırılmasıdır. GEREÇ VE YÖNTEM: Dokuz Eylül Üniversitesi Tıp Fakültesi Hayvan Deneyleri Yerel Etik Kurulu onayı alındıktan sonra ağırlıkları 250–300 g arasında değişen 28 adet erkek Wistar albino sıçan her birinde yedişer denek olacak şekilde dört gruba ayrıldı. Tüm gruplara genel anestezi altında laparotomi uygulandı ve sol renal pedikül diseke edildi. Grup I (Sham, n=7): Laparatomi sonrası sol renal pedikül diseke edilip başka bir girişim yapılmadan sıçanlar anestezi altında bekletildi. Grup II (İR, n=7): Laparotomi sonrasında sol böbreğe 45 dakika total iskemi sonrası dört saat reperfüzyon uygulandı. Grup III (İR+ Deksmedetomidin, n=7): Laparotomi sonrasında sol böbreğe İskemi uygulanırken reperfüzyonun beşinci dakikasında 100 µg/kg deksmedetomidin intraperitoneal verildi. Grup IV (UİÖK+İR, n=7): Anestezi altında sol arka bacağa üç döngü 10 dakika iskemi ve 10 dakika reperfüzyon uygulananarak beş dakika sonra sol böbrekte İR oluşturuldu. Tüm gruplarda ratların anestezi süresi eşit tutuldu, histomorfolojik değerlendirme için sol böbrek çıkarıldıktan sonra sıçanlar sakrifiye edildi. BULGULAR: Böbrek histomorfolojik hasar toplam skoru Sham grubunda diğer gruplara göre anlamlı olarak düşük bulundu (p<0.01). İskemi reperfüzyon grubundaki histomorfolojik hasar toplam skorları İR+deksmedetomidin ve UİÖK+İR gruplarından anlamlı olarak yüksek saptandı (p<0.01). Deksmedetomidin ve UİÖK gruplarının hasar skorları karşılaştırıldığında anlamlı bir fark saptanmadı (p=0.89). TARTIŞMA: Bu deneysel çalışmada, sıçan renal İR modelinde deksmedetomidin ve UİÖK’nin İR hasarını histomorfolojik olarak anlamlı düzeyde azalttığı saptanırken, İR+deksmedetomidin ve UİÖK+İR grupları arasında anlamlı bir fark bulunmadı. Anahtar sözcükler: Böbrek; deksmedetomidin; iskemi reperfüzyon hasarı; uzak iskemik ön koşullama. Ulus Travma Acil Cerrahi Derg 2017;23(4):279–286

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EXPERIMENTAL STUDY

Comparison of warm fluid and cold fluid resuscitation during uncontrolled hemorrhagic shock model in rats Serkan Dilmen, M.D.,1 Mehmet Eryılmaz, M.D.,2 Salih Müjdat Balkan, M.D.,3 Muhittin Serdar, M.D.,4 Murat Durusu, M.D.,2 Ali Osman Yıldırım, M.D.,5 Sanem Aslıhan Dilmen, M.D.6 1

Department of Cardiovascular Surgery, Gülhane Military Medical Academy, Ankara-Turkey

Department of Emergency Medicine, Gülhane Military Medical Academy, Ankara-Turkey

Department of General Surgery, TOBB ETU Hospital, Ankara-Turkey

Department of Biochemistry, Acıbadem University Faculty of Medicine, Ankara-Turkey

Department of Emergency Medicine, GATA Haydarpaşa Military Hospital, İstanbul-Turkey

Department of Physical Medicine and Rehabilitation, Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: This study was designed to compare the effects of resuscitation with cold and warm fluid on survival time, rate and volume of hemorrhage, hemodynamics, hypothermia, coagulopathy, acid-base balance, hematocrit, lactate, and base deficit during uncontrolled hemorrhagic shock (HS) model in rats. METHODS: HS model was created with splenic vascular and parenchymal injury in 29 rats under ketamine and xylazine anesthesia. Thirty minutes after the hemorrhage, the rats were randomized to receive 14.5 mL/kg 0.9% sodium chloride solution at either 24ºC (Group 1; n=9) or 4ºC (Group 2; n=10) for 20 minutes. Groups 1 and 2 were compared with group that did not receive fluid (Group 3; n=10). Statistical data were represented as mean±SD. SPSS for Windows, Version 15.0 (SPSS, Inc., Chicago, IL, USA) software, Bonferroni-adjusted Mann-Whitney U test and Kaplan-Meier procedure were used to perform statistical data analysis. P value of ≤0.05 was considered statistically significant. RESULTS: Cold fluid resuscitation decreased survival time due to increased rate and volume of hemorrhage, acidosis, hypothermia, lactate, and base deficit and decreased blood pressure and hematocrit. CONCLUSION: There is a great need for further experimental and clinical trials on fluid resuscitation in trauma in order to define which fluid should be administered, temperature of the fluid, quantity to be delivered, and duration. Keywords: Fluid resuscitation; hemorrhagic shock; intravenous cold fluid; rat.

INTRODUCTION The most common cause of death under the age of 40 years is trauma.[1] The most frequent cause of early death due to trauma is bleeding and shock.[2] In developed and developing countries, 50% to 80% of deaths due to trauma occur in the prehospital field.[3] Recent studies investigating means to Address for correspondence: Serkan Dilmen, M.D. Gülhane Askeri Tıp Akademisi, Kalp ve Damar Cerrahisi Anabilim Dalı, Keçiören, 00160 Ankara, Turkey Tel: +90 312 - 304 20 00 E-mail: drserkandilmen@hotmail.com Submitted: 17.02.2016 Accepted: 08.11.2016

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reduce mortality related to trauma have targeted the prehospital field, and have focused on fluid resuscitation as a way to reduce prehospital mortality.[4,5] The temperature of the fluid used in such resuscitation is a new area of discussion. There are numerous studies about hypothermic fluid resuscitation in non-trauma patients. This type of fluid resuscitation is included in the guidelines for management of non-trauma related cardiac arrest, but there are no clinical studies about the use of this treatment in trauma patients. Available limited experimental studies are inconclusive. In this study, it was hypothesized that cold fluid resuscitation, which has had beneficial effects in cardiac arrest patients, would also prolong survival in trauma.

MATERIALS AND METHODS The study protocol was approved by the Gülhane Military Medical Academy animal experimentation ethics commit287

Dilmen et al. Comparison of warm fluid and cold fluid resuscitation during uncontrolled hemorrhagic shock model in rats

Figure 1. Tail artery and lateral vein cannulation. Cardiocap/5 monitor and temperature probe (Model F-FML; Datex-Ohmeda, Inc., GE Healthcare Finland Oy, Helsinki, Finland).

Datex-Ohmeda, Inc., GE Healthcare Finland Oy, Helsinki, Finland) with temperature probe, and pressure monitor set (Zyron, Point Medikal San. Ve Tic. Ltd. Şti., Ankara, Turkey) were used for hemodynamic and rectal temperature (RT) monitoring (Figures 1, 2). Preparations were completed within 45 minutes, and the rats were allowed 10 minutes to become stable. Mean arterial blood pressure (MAP), heart rate (HR), RT, arterial blood gas (ABG) parameters [pH, hematocrit (HCT), lactate, base deficit], and D-dimer levels were recorded before hemorrhage was initiated. Stat Profile Critical Care Xpress blood gas analyzer (Nova Biomedical, Inc., Waltham, MA, USA) and Amax CS-190 coagulation analyzer (Trinity Biotec, Lemgo, Germany) were used for these measurements. Blood samples (0.5 mL) were collected from tail artery at 0 minute (before starting hemorrhage), 60 minutes, and every 30 minutes subsequently using heparinized syringe (BD Preset Eclipse, Belliver Industrial Estate, Plymouth, UK). After blood samples were collected, intravenous (IV) saline solution (0.5 mL) was infused in 3 minutes to replace these samples. Five minutes after recording the data, the abdominal wall of the rat was sterilized, and the abdomen was entered via a left subcostal incision. Splenic parenchymal incision was made in transverse direction at 1 level, and 1 of the 3 main branches of the splenic artery was cut (Figure 3). After allowing free flow of blood into the peritoneal cavity, abdominal incision was sutured. Thirty minutes after hemorrhage, rats were randomized to receive either 24ºC (Group 1; n=9) or 4ºC (Group 2; n=10) 0.9% sodium chloride solution (14.5 mL/kg) via infusion pump (Injectomat Agilia; Fresenius Kabi, Brezins, France) for 20 minutes (Figure 2). Quantity of fluid was chosen to simulate 1 liter of fluid for 70 kg patient since healthcare personnel can carry and administer 1 liter of fluid easily to a bleeding patient in the field. Twenty minutes was selected to simulate the time for transportation of patient from the field to the hospital. Groups 1 and 2 were compared with the control group, which did not receive fluid treatment

Figure 2. Hemodynamic and rectal temperature monitoring with Cardicap/5 monitor (Model F-FML; Datex-Ohmeda, Inc., GE Healthcare Finland Oy, Helsinki, Finland). Fluid resuscitation with infusion pump (Injectomat Agilia; Fresenius Kabi, Brezins, France).

Figure 3. Splenic parenchymal incision.

tee, on April 1, 2011 (file number 11/10). The study subjects were 30 male Sprague Dawley rats weighing between 217 and 376 g. The animals were fed commercial rat chow and provided with tap water until surgery. They were kept in cages at room temperature for more than 1 week. All of the animals were sedated with intraperitoneal injection of xylazine (4 mg/kg) and ketamine (40 mg/kg); additional doses were administered if necessary. One animal died and was excluded from the study. After sedation, the animals were placed in supine position for spontaneous breathing. After the tail was heated with an external heater to between 45ºC and 50ºC for 1 minute, the tail artery was cannulated with 26-gauge intracath (Mediﬂon; Eastern Medikit Ltd., Gurgaon, India) for hemodynamic monitoring and blood sampling, and the lateral tail vein was cannulated with 26-gauge intracath (Mediﬂon; Eastern Medikit Ltd., Gurgaon, India) for fluid resuscitation (Figure 1). Cardiocap/5 monitor (Model F-FML;

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(Group 3; n=10). The rats were observed at room temperature without any other treatment. Apnea and lack of pulse were defined as signs of death. Once death occurred, the peritoneal cavity was opened immediately, and the volume of hemorrhage was measured on a scale (Precisa Gravimetrics A.G., Dietikon, Switzerland) by calculating the difference in weight between dry gauze and gauze soaked with blood clots. MAP, HR, and RT were evaluated at 0, 30, 40, 60 minutes, and subsequently every 30 minutes until the animal died. Afterward, volume and rate of hemorrhage, and survival time were recorded. Volume of hemorrhage was calculated as percentage of total blood volume (60 mL/kg). Rate of hemorrhage was calculated as mL/kg/h. SPSS for Windows, Version 15.0 (SPSS, Inc., Chicago, IL, USA) was used to perform statistical analysis. Statistical data are presented as mean±SD. Differences between groups were analyzed using Bonferroni-adjusted Mann-Whitney U test. Differences between groups in terms of survival time were assessed using Kaplan-Meier survival analysis. In determining the number of subjects in each group, effect size of 1.52 was

estimated based on a previous study (2). Sample size of 8 subjects in each group would allow us to detect statistically significant difference with 5% Type 1 error risk and 80% power. P value of ≤0.05 was considered statistically significant.

RESULTS There were no statistically significant differences between groups in terms of weight of rats, MAP, HR, RT, ABG parameters, or D-dimer level at the beginning of the experiment (Table 1). There were statistically significant differences between groups in survival time and volume and rate of hemorrhage (Table 2) (Figure 4).

Hemodynamic Changes Thirty minutes after hemorrhage, MAP, HR, and RT decreased without significant difference in all groups. Final analysis revealed that Group 3 had significantly lower MAP and HR than Groups 1 and 2 (p<0.05). Group 1 had significantly higher MAP than Group 2 (p<0.05). There were no significant differences between Groups 1 and 2 in terms of HR. Group 3 had sig-

Table 1. Weight of rats, MAP, HR, RT, ABG parameters, and D-dimer level in the groups at the beginning of the experiment

Group 1

Group 2

Group 3

n Mean±SD n Mean±SD n Mean±SD Weight (g)

Groups 1 and 2

Groups 1 and 3

Groups 2 and 3

9 279.56±33.52 10 280.26±36.45 10 273.20±35.40 0.604 0.780 0.579

97.00±5.17 10 98.00±12.11 10 96.70±5.89 0.549 0.905 0.739 MAP (mmHg) 9 HR (beats/min) 9 343.67±48.89 10 365.08±35.15 10 340.65±49.74 0.243 0.968 0.393 RT (ºC)

9 37.18±0.20 10 37.01±0.07 10 37.07±0.14 0.065 0.278 0.436

Base deficit (mEq/L)

-1.44±0.65

-1.00±1.04

-1.65±1.14

0.278

0.497

0.247

D-dimer (ng/mL) 9 141.78±10.93 10 141.80±28.05 10 141.65±34.79 0.720 0.842 1.000 pH

9 7.41±0.03 10 7.40±0.02 10 7.40±0.02 0.842 0.661 0.853

HCT (%)

9 50.56±2.07 10 50.70±2.91 10 50.55±1.89 0.603 0.564 0.684

Lactate (mmol/L) 9 1.77±0.52 10 1.85±0.38 10 1.86±0.36 0.661 0.497 0.971 Group 1: Warm fluid therapy. Group 2: Cold fluid therapy. Group 3: Control. MAP: Mean arterial blood pressure; HR: Heart rate; RT: Rectal temperature; ABG: Arterial blood gas; HCT: Hematocrit; SD: Standard deviation.

Table 2. Survival time, volume of hemorrhage, and rate of hemorrhage in the groups

Group 1

Group 2

Group 3

n Mean±SD n Mean±SD n Mean±SD Survival time (min)

268.00±50.71

215.92±54.37

75.70±16.55

Group 1 and 2

Group 1 and 3

Groups 2 and 3

0.042

<0.001

Volume of Hemorrhage (%) 9 24.37±8.43 10 36.51±8.47 10 52.29±12.30 0.003 0.001 0.011 Rate of hemorrhage (mL/kg/h)

9 3.50±1.45 10 6.58±3.23 10 27.49±11.29

0.010

<0.001

Group 1: Warm fluid therapy. Group 2: Cold fluid therapy. Group 3: Control. SD: Standard deviation.

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Table 3. Comparison of the groups in terms of MAP, HR, RT, HCT, and D-dimer at timed intervals after hemorrhagic shock Parameters

Comparison of fluid therapies between groups

Warm* > Cold+ MAP

180

Warm > Control°

Cold > Control

Cold < Control

40, 50, 60, 90

–

Time (minute) after

HS with p<0.05

No difference

50, 90

–

40, 50, 60, 90, 120,

No difference

–

40, 50, 60, 90

150, 180, 210

HCT D-dimer

90, 120

60, 90

–

No difference

–

Warm (24 ºC) Fluid Therapy in Group 1. +Cold (4 ºC) Fluid Therapy in Group 2. °Control: Group 3. MAP: Mean arterial blood pressure; HR: Heart rate; RT: Rectal temperature; HCT: Hematocrit.

nificantly higher RT than Group 2 (p<0.05). Group 3 also had lower RT than Group 1 without significant difference. Group 1 had significantly higher RT than Group 2 (p<0.05) (Table 3).

1.0 Warm fluid therapy Cold fluid therapy Control group

ABG Parameters During the study, base deficit/lactate levels increased, and pH/ HCT levels decreased in all groups. Group 3 had significantly higher base deficit/lactate level and lower pH/HCT level than Groups 1 and 2 (Table 3 and Figures 5–7). Group 2 had significantly higher base deficit/lactate level and lower pH/HCT

Total survival rate

0.8

Base deficit (mEq/L

0.6

0.4

p<0.001

0.2

p<0.001

0.0

p=0.042

100

150 200 250 Survival time (min)

300

350

Fluid Resuscitation

Group 3

Group 1

Group 2

Lactate (mmol/L

7.30 7.20 7.10 7.00 0

120 150 180 210 240 270 300 330 Time (min)

Group 1 vs. Group 2 (p<0.05).

Group 3 vs. Group 1 and Group 2 (p<0.05)

Figure 5. PH level during hemorrhagic shock. Group 1: Warm fluid therapy. Group 2: Cold fluid therapy. Group 3: Control.

290

Time (min) 30

120 150 180 210 240 270 300 330

Group 3

Group 1

Group 2

Group 3 vs. Group 1 and Group 2 (p<0.05)

Figure 6. Base deficit level during hemorrhagic shock. Group 1: Warm fluid therapy. Group 2: Cold fluid therapy. Group 3: Control.

7.40

6.90

Fluid Resuscitation

Group 1 vs. Group 2 (p<0.05).

Figure 4. Cumulative survival (Kaplan-Meier) during hemorrhagic shock.

7.50

2 0 -2 0 -4 -6 -8 -10 -12 -14 -16 -18 -20 -22 -24

18.0 17.0 16.0 15.0 14.0 13.0 12.0 11.0 10.0 9.0 8.0 7.0 6.0 9.0 9.0 9.0 9.0 9.0

Group 3

Group 1

Group 2

Fluid Resuscitation

120 150 180 210 240 270 300 330 Time (min)

Group 1 vs. Group 2 (p<0.05).

Group 3 vs. Group 1 and Group 2 (p<0.05)

Figure 7. Lactate level during hemorrhagic shock. Group 1: Warm fluid therapy. Group 2: Cold fluid therapy. Group 3: Control.

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Dilmen et al. Comparison of warm fluid and cold fluid resuscitation during uncontrolled hemorrhagic shock model in rats

level than Group 1 (Table 3 and Figures 5–7). D-dimer: No statistically significant difference was determined between groups in D-dimer level (Table 3).

DISCUSSION The primary finding of the present study was that warm fluid resuscitation had more beneficial effects on survival than cold fluid resuscitation. Many clinical and experimental studies focusing on prehospital cardiac arrest have demonstrated that cold fluid resuscitation positively contributes to survival time, hemodynamics, acid-base balance, and neurological and renal functions.[6–9] Conversely, we observed deleterious effects of this treatment in trauma-related hemorrhagic shock (HS). In the literature, there are only 2 studies that compare fluid resuscitation at different temperatures in HS model, and both of these were pig models.[2,10] Our study is the first to be conducted using rats. Norio et al.[2] reported that cold fluid infusion increased survival time. They thought this was a result of therapeutic hypothermia, which decreased HR and stroke volume index, and thus reduced oxygen demand of the heart. [2] In contrast, we found that cold fluid infusion decreased survival time. Cold fluid infusion may have increased volume and rate of hemorrhage, hypothermia, and acidosis, which might be related to poor tissue perfusion by causing vasoconstriction. As we did, Wu et al.[10] found that cold fluid infusion decreased survival time compared with warm fluid infusion, but they also detected that 2ºC and 24ºC fluid infusions increased survival time compared with 38ºC fluid infusion due to therapeutic hypothermia (34ºC).[10] In our study, increasing volume and rate of hemorrhage in cold fluid infusion group might be due to hypothermic coagulopathy. This coagulopathy might be explained by hypothermia below 34ºC, which results in platelet dysfunction, inhibition of protein kinase D, and increased prostacyclin synthesis.[2,11] Norio et al.[2] did not find significant differences between groups in terms of volume of hemorrhage. They attributed this finding to stable body temperature of 35.5ºC in cold fluid infusion group, and thus, did not encounter any hypothermic coagulopathy. While Norio et al. and Wu et al.[2,10] didn’t indicate significant differences between groups in terms of MAP, we found that cold fluid infusion decreased MAP. Cold fluid infusion may have increased hypothermia and acidosis, and thus decreased MAP due to cardiac arrhythmia and low cardiac output. While these studies determined lower HR in cold fluid infusion groups, we didn’t find a significant difference between treatment groups in terms of HR. They considered low HR to be result of protective effect of hypothermia on heart.[2,10] Unlike those studies, we observed that HR after treatment didn’t remain at stable level, and always fell. This result can be explained by HR decreases in rats based on parasympathetic activation, instead of sympathetic activation in the heart, when blood pressure falls. [12,13] Norio et al.[2] found cold fluid infusion increased HCT, and attributed this finding to hypothermia-induced hemoconcentration generated by plasma leakage into extravascular Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

spaces. We observed that cold fluid infusion decreased HCT. We think this finding may have been due to greater volume and rate of hemorrhage in cold fluid infusion group. While Norio and Wu et al.[2,10] didn’t report significant differences between groups in terms of pH and base deficit, we found that cold fluid infusion decreased pH and increased lactate and base deficit levels as result of acidosis. As in our study, Wu et al.[10] found that cold fluid infusion increased lactate levels with acidosis. However, there was no correlation between lactate and base deficit levels in their study. Normally, base deficit increases when lactate increases. After treatment of HS, lactate and base deficit are expected to decrease.[14] Conversely, the previous authors indicated base deficit and lactate levels increased after treatment. There were also other differences in materials and methods used in our study in comparison with these 2 studies. They included volume-controlled hemorrhagic stage, which did not totally represent an uncontrolled HS model, and thus did not simulate trauma very well.[15,16] These studies simulated hospital phase more than prehospital phase, as they incorporated mechanical ventilation and intensive care. We excluded this stage to simulate prehospital phase for trauma patients. There was also no control group in those studies. Furthermore, coagulopathy, one of the parameters of the “lethal triad” in HS, was not evaluated.[2,10] In a previous study conducted by Zhang et al.,[17] it was reported that D-dimer might be prognostic factor in a rat model of HS. We used D-dimer, a fibrin degradation product, to assess coagulopathy; however, there was no significant difference in D-dimer level between groups. We think D-dimer may not be a suitable parameter for evaluation coagulopathy since there are some differences between humans and rats in terms of coagulation system.[18] We believe that further studies are required to demonstrate relationship between D-dimer and coagulopathy during HS. In addition to our main findings, interestingly, we found that compared with the control group, both treatment groups had smaller volume and lower rate of hemorrhage, and thus had higher MAP, HR, HCT, and pH, as well as lower lactate and base deficit. This result could be explained by the fact that infusions were colder than body temperature and therefore caused vasoconstriction, and/or volume of fluid used in resuscitation was less than has been used in other studies.[19–23] Other studies found aggressive fluid therapy at dose of 3570 mL/kg increased volume and rate of hemorrhage because it caused dilutional coagulopathy, hypothermia, disruption of thrombus formation, higher blood pressure, and inhibition of vasoconstriction.[19–23] Low dose (14.5 mL/kg) of fluid may decrease volume and rate of hemorrhage. As a result, we think that crystalloid fluid resuscitation at dose of 14.5 mL/kg for 20 minutes, even at different temperatures, can have beneficial effects on survival.

Limitations The limitations of the present study are lack of large animal 291

Dilmen et al. Comparison of warm fluid and cold fluid resuscitation during uncontrolled hemorrhagic shock model in rats

model and of hot fluid resuscitation group. We may not have simulated real clinical situations using small animal model. For example, rats are more prone to hypothermia than pigs. We observed deep hypothermia (25ºC) instead of therapeutic hypothermia (34ºC) during the experiment. Anesthetic agents, fluids that were colder than body temperature, exposure to room temperature, HS, and laparotomy might have also triggered deep hypothermia in rats. In theory, HS patients should receive fluid resuscitation at body temperature to prevent hypothermia.[24] If we could have added 37ºC hot fluid infusion group to our study, we would have been able to better compare efficiency of fluid therapies at different temperature.

Conclusion Cold fluid resuscitation decreased survival time because it increased rate and volume hemorrhage, acidosis, and hypothermia. During pre-hospital phase (the time before patient arrival to hospital), also known as the “golden hour,” fluid resuscitation should be administered immediately in order to decrease mortality. Additional experimental studies, especially including large animal models and clinical studies, are needed to further examine fluid resuscitation, including temperature and type of fluid, quantity of fluid to be provided, and duration of administration by evaluating effects on acidosis, coagulopathy, and hypothermia. Conflict of interest: None declared.

REFERENCES 1. Faist E, Baue AE, Dittmer H, Heberer G. Multiple organ failure in polytrauma patients. Journal of Trauma 1983;23:775–8. 2. Norio H, Takasu A, Kawakami M, Saitoh D, Sakamoto T, Okada Y. Rapid body cooling by cold fluid infusion prolongs survival time during uncontrolled hemorrhagic shock in pigs. J Trauma 2002;52:1056–61. 3. Ertekin C. Approach to the patient with multiple trauma. Turkish Journal of Intensive Care Medicine 2002;2(2):77–87. 4. Bilkovski RN, Rivers EP, Horst HM. Targeted resuscitation strategies after injury. Curr Opin Crit Care 2004;10:529–38. 5. Mapstone J, Roberts I, Evans P. Fluid resuscitation strategies: a systematic review of animal trials. J Trauma 2003;55:571–89. 6. Kliegel A, Losert H, Sterz F, Kliegel M, Holzer M, Uray T, et al. Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest--a feasibility study. Resuscitation 2005;64:347–51. 7. Kämäräinen A, Virkkunen I, Tenhunen J, Yli-Hankala A, Silfvast T. Induction of therapeutic hypothermia during prehospital CPR using icecold intravenous fluid. Resuscitation 2008;79:205–11. 8. Polderman KH, Rijnsburger ER, Peerdeman SM, Girbes AR. Induc-

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tion of hypothermia in patients with various types of neurologic injury with use of large volumes of ice-cold intravenous fluid. Crit Care Med 2005;33:2744–51. 9. Bernard S, Buist M, Monteiro O, Smith K. Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-ofhospital cardiac arrest: a preliminary report. Resuscitation 2003;56:9– 13. 10. Wu X, Kochanek PM, Cochran K, Nozari A, Henchir J, Stezoski SW, et al. Mild hypothermia improves survival after prolonged, traumatic hemorrhagic shock in pigs. J Trauma 2005;59:291–301. 11. Dogan Z. Retrospective Analysis of the pediatric patients with trauma presenting to emergency service. Emergency medicine specialty thesis. Cumhuriyet University Medical Faculty Emergency Department, Sivas 2008. 12. Little RA. 1988 Fitts lecture: heart rate changes after haemorrhage and injury--a reappraisal. J Trauma 1989;29:903–6. 13. Secher NH, Sander Jensen K, Werner C, Warberg J, Bie P. Bradycardia during severe but reversible hypovolemic shock in man. Circ Shock 1984;14:267–74. 14. Kline JA. Shock. In: Marx JA, editor. Rosens’s Emergency Medicine Concepts and Clinical Practice. 7th ed. Mosby: St Louis; 2010. p. 34–41. 15. Durusu M, Eryilmaz M, Oztürk G, Menteş O, Ozer T, Deniz T. Comparison of permissive hypotensive resuscitation, low-volume fluid resuscitation, and aggressive fluid resuscitation therapy approaches in an experimental uncontrolled hemorrhagic shock model. Ulus Travma Acil Cerrahi Derg 2010;16:191–7. 16. Lomas-Niera JL, Perl M, Chung CS, Ayala A. Shock and Hemorrhage: An Overview of Animal Models. Shock 2005;24:33–9. 17. Zhang YJ, Pan JY, Wang MS. Study on changes of blood coagulation factors in rats with hemorrhagic shock. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2005;13:110–3. 18. Prueckner S, Safar P, Kentner R, Stezoski J, Tisherman SA. Mild hypothermia increases survival from severe pressure-controlled hemorrhagic shock in rats. J Trauma 2001;50:253–62. 19. Solomonov E, Hirsh M, Yahiya A, Krausz MM. The effect of vigorous fluid resuscitation in uncontrolled hemorrhagic shock after massive splenic injury. Crit Care Med 2000;28:749–54. 20. Hatoum OA, Bashenko Y, Hirsh M, Krausz MM. Continuous fluid resuscitation for treatment of uncontrolled hemorrhagic shock following massive splenic injury in rats. Shock 2002;18:574–9. 21. Krausz MM, Bashenko Y, Hirsh M. Crystalloid or colloid resuscitation of uncontrolled hemorrhagic shock after moderate splenic injury. Shock 2000;13:230–5. 22. Krausz MM, Bashenko Y, Hirsh M. Crystalloid and colloid resuscitation of uncontrolled hemorrhagic shock following massive splenic injury. Shock 2001;16:383–8. 23. Bickell WH, Wall MJ Jr, Pepe PE, Martin RR, Ginger VF, Allen MK, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:1105–9. 24. Baykal Y. Book of the Month: Shock and Treatment. In: Baykal Y, Erikci S, Azal O, Karaayvaz M, Zeybek N, Editors. Ankara: GATA Publication House; 2001. p. 101–10.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçanlarda oluşturulan kontrolsüz hemorajik şok modelinde ılık sıvı ile soğuk sıvı resüsitasyonlarının karşılaştırılması Dr. Serkan Dilmen,1 Dr. Mehmet Eryılmaz,2 Dr. Salih Müjdat Balkan,3 Dr. Muhittin Serdar,4 Dr. Murat Durusu,2 Dr. Ali Osman Yıldırım,5 Dr. Sanem Aslıhan Dilmen6 Gülhane Askeri Tıp Akademisi, Kalp ve Damar Cerrahisi Anabilim Dalı, Ankara Gülhane Askeri Tıp Akademisi, Acil Tıp Anabilim Dalı, Ankara Özel TOBB ETÜ Hastanesi, Genel Cerrahi Kliniği, Ankara 4 Acıbadem Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Ankara 5 Gülhane Askeri Tıp Akademisi Haydarpaşa Asker Hastanesi, Acil Tıp Anabilim Dalı, İstanbul 6 Ankara Fizik Tedavi ve Rehabilitasyon Eğitim ve Araştırma Hastanesi, Fizik Tedavi ve Rehabilitasyon Kliniği, Ankara 1 2 3

AMAÇ: Bu çalışma, sıçanlarda oluşturulan kontrolsüz hemorajik şok (HŞ) modelinde, soğuk sıvı resüsitasyonunun yaşam süresi, kanama miktarı, kanama hızı, hemodinami, hipotermi, koagülopati, asit-baz dengesi, hematokrit, laktat ve baz defisit üzerine etkilerini, ılık sıvı resüsitasyonunun etkileriyle karşılaştırmak için planlandı. GEREÇ VE YÖNTEM: Çalışmada ketamin ve ksilazinle anestezi altına alınan 29 sıçanın dalağında, vasküler ve parankim yaralanması ile HŞ modeli oluşturuldu. Hemorajik şokun 30. dakikasında, sıçanlara randomize olarak, 14.5 ml/kg dozunda %0.9 NaCl solüsyonu, 24 ºC sıcaklıkta (Grup 1, n=9) ve 4 ºC sıcaklıkta (Grup 2, n=10) 20 dakika süreyle intravenöz infüze edildi. Grup 1 ve 2’nin tedavi etkinliği, sıvı tedavisi uygulanmayan grupla (Grup 3, n=10) karşılaştırıldı. İstatistiksel olarak veriler, ortalama±standart sapma olarak hesaplandı. İstatistiksel analiz için SPSS for Windows 15.0 programı, Bonferroni düzeltmeli Mann-Whitney U-testi ve Kaplan-Meier prosedürü kullanıldı. P≤0.05 olduğunda, istatistiksel olarak anlamlı kabul edildi. BULGULAR: Soğuk sıvı resüsitasyonu kanama miktarını, kanama hızını, asidozu, hipotermiyi, laktatı, baz defisitini artırarak ve de kan basıncını, hematokriti düşürerek yaşam süresini kısaltmıştır. TARTIŞMA: Travmada sıvı resüsitasyonu ile ilgili olarak; hangi sıvının, hangi sıcaklıkta, hangi miktarda ve ne kadar sürede verileceğini inceleyen birçok deneysel ve klinik çalışmaların planlanmasına büyük ihtiyaç olduğu değerlendirilmiştir. Anahtar sözcükler: Hemorajik şok; intravenöz soğuk sıvı; sıçan; sıvı resüsitasyonu. Ulus Travma Acil Cerrahi Derg 2017;23(4):287–293

doi: 10.5505/tjtes.2016.50487

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ORIGIN A L A R T IC L E

The value of internal jugular vein collapsibility index in sepsis Murat Haliloğlu, M.D., Beliz Bilgili, M.D., Alper Kararmaz, M.D., İsmail Cinel, M.D. Department of Anesthesiology and Reanimation, Marmara University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Rapid, accurate, and reproducible assessment of intravascular volume status is crucial in order to predict the efficacy of volume expansion in septic patients. The aim of this study was to verify the feasibility and usefulness of the internal jugular vein collapsibility index (IJV-CI) as an adjunct to the inferior vena cava collapsibility index (IVC-CI) to predict fluid responsiveness in spontaneously-breathing patients with sepsis. METHODS: Three stages of sonographic scanning were performed. Hemodynamic data were collected using the Ultrasonic Cardiac Output Monitor 1A system (Uscom, Ltd., Sydney, NSW, Australia) coupled with paired assessments of IVC-CI and IJV-CI at baseline, after passive leg raise (PLR), and again in semi-recumbent position. Fluid responsiveness was assessed according to changes in the cardiac index (CI) induced by PLR. Patients were retrospectively divided into 2 groups: fluid responder if an increase in CI (ΔCI) ≥15% was obtained after PLR maneuver, and non-responder if ΔCI was <15%. RESULTS: Total of 132 paired scans of IJV and IVC were completed in 44 patients who presented with sepsis and who were not receiving mechanical ventilation (mean age: 54.6±16.1 years). Of these, 23 (52.2%) were considered to be responders. Responders had higher IJV-CI and IVC-CI before PLR maneuver than non-responders (p<0.001). IJV-CI of more than 36% before PLR maneuver had 78% sensitivity and 85% specificity to predict responder. Furthermore, less time was needed to measure venous diameters for IJV-CI (30 seconds) compared with IVC-CI (77.5 seconds; p<0.001). CONCLUSION: IJV-CI is a precise, easily acquired, non-invasive parameter of fluid responsiveness in patients with sepsis who are not mechanically ventilated, and it appears to be a reasonable adjunct to IVC-CI. Keywords: Collapsibility index; fluid therapy; inferior vena cava; internal jugular vein.

INTRODUCTION Sepsis is associated with decreased effective blood volume, and fluid resuscitation is usually recommended to increase cardiac output and improve tissue hypoperfusion.[1] However, studies have shown a relationship between positive fluid balance and mortality in patients with sepsis.[2] Therefore, rapid, accurate, and reproducible assessment of intravascular volume status is crucial in order to predict the efficacy of volume expansion.[3] Address for correspondence: Beliz Bilgili, M.D. Marmara Üniversitesi Tıp Fakültesi, Anesteziyoloji Anabilim Dalı, Üst Kaynarca, Pendik, İstanbul, Turkey Tel: +90 216 - 625 45 45 E-mail: belizbilgili@gmail.com Submitted: 25.07.2016 Accepted: 08.11.2016

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The inferior vena cava collapsibility index (IVC-CI) has been shown to correlate with both clinical and invasive assessment of intravascular volume status and has become increasingly popular.[4] It is very easy to record and has a short learning curve. However, IVC measurements are not possible in 10% to 15% of patients because of abdominal distension, ascites, bowel gas, tissue edema, complex abdominal wounds, or morbid obesity.[5] A body of evidence indicates that extrathoracic veins can reflect intrathoracic venous pressure and volume changes.[6] Based on this association, hypothesis of this study was that internal jugular vein collapsibility index (IJV-CI) could be an alternative sonographic option to IVC-CI. Prospective examination of the efficacy of the IJV-CI as an alternative in the absence of adequate IVC visualization was performed.

MATERIALS AND METHODS After receiving institutional review board approval, a prospective, observational clinical trial was conducted in the surgical intensive care unit (SICU) at a university hospital. Marmara University ethics committee approval (No: 09.2015.288) was granted, written informed consent was obtained from the paUlus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

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tients, and the study was conducted in accordance with the Declaration of Helsinki, including current revisions and Good Clinical Practice guidelines. Hemodynamic data obtained from 44 patients presenting sepsis, according to the definition of and treated following the indications of Surviving Sepsis Campaign Guidelines.[1] All patients were enrolled within 6 hours of the time of admission to SICU and were not receiving mechanical ventilation. The patients signed informed consent form prior to initiation of study-related activities. Collected data included patient demographics (age, sex), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology And Chronic Health Evaluation (APACHE II) score, laboratory values, hemodynamic parameters, and sonographic measurements of IVC and IJV collapsibility. Exclusion criteria were age <18 years, pregnancy, severe aortic stenosis, irregular ventricular rhythm (atrial fibrillation or frequent premature ventricular contractions), or any contraindication to performing passive leg raise (PLR) (intracranial hypertension, intraabdominal hypertension, body mass index >40 kg/m2, deep venous thrombosis, use of venous elastic compression stockings, or limb and pelvic fracture). Hemodynamic data and paired sonographic measurements of IVC and IJV were collected simultaneously; measurements were performed by single operator. All patients in this study underwent serial, simultaneous assessments of IVC-CI and IJVCI using Philips EPIQ 5 ultrasound system (Philips Healthcare, Inc., Andover, MA, USA). Ultrasonographic examination was performed with standard curvilinear phased array transducer via initial B-mode paramedian longitudinal window of the IVC just proximal to the junction of the hepatic veins that lie approximately 0.5 cm to 3 cm proximal to the right atrium.[4] IJV was visualized with high-frequency linear array transducer via cross-sectional B-mode window of the short axis of the vessel at the level of the cricoid cartilage and recognized by compression, color Doppler, and pulsed-wave Doppler sampling. In order to avoid changes in vein diameter unrelated to respiratory variation, minimal pressure was applied to the probe to ensure that venous occlusion did not occur.[7] Dynamic diameter changes of the target vein were recorded using Mmode to measure maximum and minimum dimensions over 20-second period of spontaneous respiration. Vein collapsibil-

ity was calculated using the following formula: collapsibility (%) = (max diameter - min diameter) / max diameter.[8,9] For each scan, time to data acquisition was defined as time from probe placement to vessel measurement recording. Hemodynamic data were collected using Ultrasonic Cardiac Output Monitor (USCOM) 1A system (Uscom Ltd., Sydney, NSW, Australia), coupled with paired assessments of IVC-CI and IJV-CI. The study protocol was performed in 3 sequential stages. Baseline parameters were recorded with the patient in semirecumbent position. Next, PLR maneuver was performed by placing the patient in supine position and simultaneously raising the patient’s legs to 45°, and after 1 minute, second measurement was recorded. Third measurement was performed 2 minutes after the patient had been moved back to semi-recumbent position in order to check that measured parameters had returned to baseline. The study protocol is shown in Figure 1. Fluid responsiveness was assessed through changes in cardiac index (CI) induced by PLR. Patients were retrospectively divided into 2 groups: fluid responders, if increase in CI (ΔCI) of ≥15% was obtained after PLR maneuver, and non-responders if ΔCI was <15%, as previously described.[10]

Statistical Analysis R v.215.3 (R Core Team, 2013; R Foundation for Statistical Computing, Vienna, Austria) software was used to perform statistical analyses. Data were reported as mean, standard deviation, median, first quartile, third quartile, frequency, percentage, minimum and maximum. Student’s t-test was used to assess difference of normally distributed variables between the 2 groups. Mann-Whitney U test was used to test difference of non-normally distributed variables between groups. Paired t-test was applied to analyze difference between IVC and IJV values. Receiver operating characteristic (ROC) curves were constructed, sensitivity and specificity of variables were calculated for various values, and value with highest Youden index value was taken as cut-off point. Pearson’s correlation coefficient was used to test association between variables. Paired, concurrent measurements of IVC-CI and IJV-CI were analyzed using correlation coefficient and Bland-Altman bias plot. Statistical significance was defined as p<0.05.

45°

45° Stage 1: Head elevated at 45° for 2 minutes before obtaining indices as the baseline.

Stage 2: Supine position with legs elevated at 45° for 1 minute before obtaining the indices

45° Stage 3: Baseline position kept for 2 minutes before obtaining indices

Figure 1. Study protocol.

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It was assumed that IVC-CI would be clinically relevant if 95% confidence interval of area under the curve (AUC) was >0.75, corresponding to AUC of good clinical tool as reported by Ray et al.[11] Inclusion of 39 patients was required to achieve this purpose. Bootstrap analysis was used to calculate precise confidence intervals. Bootstrapping is a method for assigning measures of accuracy to sample estimates and allows estimation of the sampling distribution. [12] Five patients were added to account for possible missing data.

RESULTS Total of 44 nonintubated, nonventilated, spontaneously breathing patients with sepsis were examined. Of those, 23 (52.3%) patients were considered to be responders, with increase in CI of 15% or more after PLR maneuver. There were no significant differences between responders and nonresponders with regard to demographic or baseline clinical characteristics (Table 1). Hemodynamic and ultrasonographic measurements are re-

Table 1. Characteristics of the study population

Responders (n=23)

Non-responders (n=21)

64.65±11.28

66.10±16.40

0.734

43.47

42.85

0.716

Body mass index

32.22±7.49

33.14±7.56

0.686

APACHE II

16 (15.17)

0.875

8 (7.10)

9 (8.10)

0.146

Age (years) Gender (% female)

SOFA

Data are presented as median (Q1, Q3) where Q1: first quartile and Q3: third quartile. APACHE: Acute Physiology And Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment.

Table 2. Variations in hemodynamic parameters measured in responders and non-responders

Responders (n=23)

Non-responders (n=21)

Mean±SD

Heart rate (beats/minute)

Stage 1

83.35±5.88

82.43±5.34

0.231

Stage 2

81.78±5.38

81.24±5.25

0.736

Stage 3

84.87±5.83

83.14±5.79

0.342

Mean arterial pressure (mmHg)

Stage 1

68.22±5.83

70.86±8.44

0.451

Stage 2

76.57±7.23

80.67±8.91

0.100

Stage 3

67.43±5.37

70.90±8.50

0.464

Cardiac index (L/minute/M2)

Stage 1

2.26±0.11

2.31±0.18

0.326

Stage 2

3.03±0.17

2.98±0.18

0.287

Stage 3

2.30±0.12

2.32±0.20

0.756

IVC-CI (%)

Stage 1

37.17±9.02

25.29±8.25

<0.001***

Stage 2

17.61±2.74

17.62±2.87

0.812

Stage 3

35.00±8.72

26.05±7.56

<0.001***

IJV-CI (%)

Stage 1

39.04±8.42

26.71±7.04

<0.001***

Stage 2

18.83±2.84

18.62±2.89

0.990

Stage 3

38.61±8.74

27.33±6.48

Data are presented as median (Q1, Q3) where Q1: first quartile and Q3: third quartile. p<0.05; p<0.01; vena cava collapsibility index; IJV-CI: Internal jugular vein collapsibility index; SD: Standard deviation. *

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0.001*** p<0.001. IVC-CI: Inferior

***

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ported in Table 2. In 3 stages, heart rate (HR), mean arterial pressure (MAP), and CI did not differentiate responders from non-responders. Responders had higher IJV-CI and IVC-CI than non-responders at stage 1 (p<0.001). This difference was lost after the PLR maneuver at stage 2. Responders also had higher IJV-CI and IVC-CI than non-responders at stage 3 (p=0.001, p<0.001, respectively). Total of 132 paired measurements of IJV-CI and IVC-CI were performed. On average, it took 47.5 seconds less to acquire IJV-CI measurements than paired IVC-CI measurements. Mean time to data acquisition was 30 seconds (range: 25-45 1.0

Sensitivity

0.8

seconds) for IJV-CI versus 77.5 seconds for IVC-CI (range: 65-100 seconds; p<0.01). Cut-off values and corresponding sensitivity and specificities of IJV-CI at stage 1 were measured to distinguish responders and non-responders. Cut-off value was determined to be IJC-CI ≥36 according to highest Youden index, with 0.78% sensitivity and 0.85% specificity. Area under the ROC curve (AUC) for IJV-CI was 0.872 (Figure 2). Cut-off values and corresponding sensitivity and specificities of IVC-CI at stage 1 were measured to distinguish responders and non-responders. Cut-off value was determined to be IVCCI ≥35 according to highest Youden index, with 0.78% sensitivity and 0.85% specificity. AUC for IVC-CI was 0.825 (Figure 3). On linear regression analysis, paired measurements demon-

0.6 60 0.4

IJV.CI

0.2

0.0 0.0

R square = 0.953

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 2. Receiver operating characteristic curve for discriminating responders from non-responders after passive leg raise. The solid line indicates area under curve for internal jugular vein collapsibility index at stage 1 of 0.825; p<0.001.

1.0

40 30 20 10 10

IVC.CI

Figure 4. Inferior vena cava collapsibility index versus internal jugular vein collapsibility index. Linear regression demonstrates acceptable correlation between the 2 measurement modalities (R2=0.953). IJV-CI: Internal jugular vein collapsibility index; IVCCI: Inferior vena cava collapsibility index.

0.8

0.6 Difference (IVC-IJV)

Sensitivity

0.4

0.2

0.0 0.0

-5

-10

-15 0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 3. Receiver operating characteristic curve for discriminating responders from non-responders after passive leg raise. The solid line indicates area under curve for inferior vena cava collapsibility index at stage 1 of 0.825; p<0.001.

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30 40 Average collapsibility

Figure 5. Measurement bias plot comparing inferior vena cava collapsibility index and internal jugular vein collapsibility index across a broad range of collapsibility values. IJV-CI: Internal jugular vein collapsibility index; IVC-CI: Inferior vena cava collapsibility index.

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HaliloÄ&#x;lu et al. The value of internal jugular vein collapsibility index in sepsis

strated acceptable correlation over a broad range of venous collapsibility values (R2=0.953; Figure 4). As a result of the regression analysis, measurement bias was not observed on Bland-Altman graphics. Also, there was a positive correlation between IVC-CI and IJV-CI values (r=0.976; R2:0.953) (Figure 5).

DISCUSSION Results of this study demonstrated that IJV collapsibility was a precise, easily acquired non-invasive parameter of fluid responsiveness in spontaneously breathing patients with sepsis and appeared to be a reasonable adjunct to IVC-CI. Additionally, it took less time to acquire IJV-CI measurements than IVC-CI measurements. USCOM is a non-invasive continuous-wave (CW) Doppler ultrasound device, temporarily placed in the suprasternal notch to measure Doppler flow at the aortic valve over a cardiac cycle (velocity time integral, VTI). Valve cross-sectional area is determined by applying height-indexed regression equations, and then stroke volume is calculated by multiplying the VTI by the estimate of cross-sectional area.[13] The Surviving Sepsis Campaign still recommends central venous pressure (CVP) as a guide for fluid infusion.[1] However, right-sided filling pressure and CVP measurement require a central venous catheter, which delays resuscitation and is associated with numerous potential complications.[14] Studies have concluded that there was good correlation between right atrial pressure and IVC respiratory variability in spontaneously breathing patients.[15,16] Studies that compared IVC measurements and central venous pressure have reported that diameter of the IVC correlated directly to CVP in mechanically-ventilated patients with sepsis, and the IVC-CI correlated with CVP in the setting of low and high CI ranges. [8,17] Brennan et al. demonstrated that cut-off value of 20% for passive IVC-CI and cut-off value 40% in the sniff test were able to identify patientsâ&#x20AC;&#x2122; right atrial pressure values less than and greater than 10 mmHg.[18] Additionally, it has been shown that IVC variations were closely correlated with cardiac output increase after fluid infusion.[19,20] Muller et al. analyzed respiratory variations of IVC to predict fluid responsiveness in spontaneously-breathing patients with acute circulatory failure.[21] The authors concluded that IVC-CI >40% permitted the prediction of fluid responsiveness, but also IVC-CI <40% did not rule out fluid needs. A body of evidence shows that extrathoracic veins can reflect intrathoracic venous pressure and volume changes.[6,22] Based on this association, we hypothesized that IJV-CI could be an alternative sonographic option to IVC-CI. Though several studies have examined IVC-CI and IJV-CI individually to evaluate intravascular volume status and CVP, scarce data exist on the relationship between IVC-CI and IJV-CI. One of our questions was whether IJV-CI and IVC-CI could be used 298

interchangeably in the setting of spontaneous breathing. Kent et al. studied the feasibility of femoral vein (FV) or IJV collapsibility as options in intravascular volume status assessment and concluded that correlation between IVC-CI and FV/IJV-CI was weak.[23] However, patients were predominately (72%) mechanically ventilated in their study. Another study from the USA demonstrated that IJV-CI and IVC-CI correlated during spontaneous breathing, but found no statistical correlation during increased thoracic and intra-abdominal pressure.[24] PLR maneuver mimics an endogenous fluid challenge by transferring around 300 mL of venous blood from the lower body toward the right heart.[25] PLR is a reversible maneuver, thereby avoiding the risks of volume overload.[26] We assessed changes in CI induced by PLR maneuver as an indicator of fluid responsiveness in patients with sepsis who were not receiving mechanical ventilation. In the present study, IJV-CI was measured to calculate a cutoff of 36%, with sensitivity of 78% and specificity of 86% to predict volume response in spontaneously breathing patients with sepsis. Similarly, we also demonstrated IVC-CI threshold values of 35% to discriminate responders from non-responders with sensitivity of 78% and specificity of 86%. As in our study, the literature has verified that IJV-CI greater than 39% was strongly associated with overall patient hypovolemia.[27,28] In the current study, cut-off values of similar parameters are somewhat higher than values reported in mandatory ventilated patients.[9,20,29] Increased efficiency in patients not mechanically ventilated may result in decreased delta to intrathoracic pressure for comparable tidal volume, and so may require a larger signal to achieve a comparable effect.[30] We excluded mechanically ventilated patients because net effect of intrathoracic pressure change may be difficult to assess and collapsibility index may be affected by the amount of diaphragmatic excursion vs. the amount of chest excursion. [31,32] These data suggest that collapsibility index poorly predicts volume responsiveness in this population. Our study has several limitations. First, all measurements were performed by a single operator, interobserver variability in sonographic venous diameter measurement remains to be assessed in future studies. Secondly, we did not include patients with cardiac disease. Thirdly, changes in CVP influence IJV diameter and may decrease relative collapsibility. Increased intraabdominal or intrathoracic pressure may increase CVP, which can lead to reduced IJV-CI, independent of preload responsiveness. Of 44 enrolled patients, only 5 patients had CVP catheters. In that case, we did not study the effect of high CVP on IJV-CI and IVC-CI. Therefore, in this study, any confounding conditions, such as cardiac disease, and increased thoracic and intraabdominal pressure were excluded. Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

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IJV-CI is a precise, easily acquired, non-invasive parameter of fluid responsiveness in spontaneously breathing patients with sepsis who are not mechanically ventilated. IJV-CI also appears to be a reasonable adjunct to IVC-CI. Furthermore, obtaining IJV-CI measurements requires less time than IVC-CI measurements, which is another advantage. Conflict of interest: None declared.

REFERENCES 1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165–228. 2. Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care 2015;19:251. 3. Dellinger RP. Foreword. The Future of Sepsis Performance Improvement. Crit Care Med 2015;43:1787–9. 4. Seif D, Perera P, Mailhot T, Riley D, Mandavia D. Bedside ultrasound in resuscitation and the rapid ultrasound in shock protocol. Crit Care Res Pract 2012;2012:503254. 5. Nagdev AD, Merchant RC, Tirado-Gonzalez A, Sisson CA, Murphy MC. Emergency department bedside ultrasonographic measurement of the caval index for noninvasive determination of low central venous pressure. Ann Emerg Med 2010;55:290–5. 6. Constant J. Using internal jugular pulsations as a manometer for right atrial pressure measurements. Cardiology 2000;93:26–30. 7. Prekker ME, Scott NL, Hart D, Sprenkle MD, Leatherman JW. Pointof-care ultrasound to estimate central venous pressure: a comparison of three techniques. Crit Care Med 2013;41:833–41. 8. Stawicki SP, Braslow BM, Panebianco NL, Kirkpatrick JN, Gracias VH, Hayden GE, et al. Intensivist use of hand-carried ultrasonography to measure IVC collapsibility in estimating intravascular volume status: correlations with CVP. J Am Coll Surg 2009;209:55–61. 9. Vieillard-Baron A, Chergui K, Rabiller A, Peyrouset O, Page B, Beauchet A, et al. Superior vena caval collapsibility as a gauge of volume status in ventilated septic patients. Intensive Care Med 2004;30:1734–9. 10. Michard F, Boussat S, Chemla D, Anguel N, Mercat A, Lecarpentier Y, et al. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med 2000;162:134–8. 11. Ray P, Le Manach Y, Riou B, Houle TT. Statistical evaluation of a biomarker. The Journal of the American Society of Anesthesiologists 2010;112:1023–40. 12. Carpenter J, Bithell J. Bootstrap confidence intervals: when, which, what? A practical guide for medical statisticians. Stat Med 2000;19:1141–64. 13. Nidorf SM, Picard MH, Triulzi MO, Thomas JD, Newell J, King ME, et al. New perspectives in the assessment of cardiac chamber dimensions during development and adulthood. J Am Coll Cardiol 1992;19:983–8. 14. Taylor RW, Palagiri AV. Central venous catheterization. Crit Care Med 2007;35:1390–6. 15. Mintz GS, Kotler MN, Parry WR, Iskandrian AS, Kane SA. Real-time inferior vena caval ultrasonography: normal and abnormal findings and its use in assessing right-heart function. Circulation 1981;64:1018–25. 16. Moreno FL, Hagan AD, Holmen JR, Pryor TA, Strickland RD, Castle

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CH. Evaluation of size and dynamics of the inferior vena cava as an index of right-sided cardiac function. Am J Cardiol 1984;53:579–85. 17. Schefold JC, Storm C, Bercker S, Pschowski R, Oppert M, Krüger A, et al. Inferior vena cava diameter correlates with invasive hemodynamic measures in mechanically ventilated intensive care unit patients with sepsis. J Emerg Med 2010;38:632–7. 18. Brennan JM, Blair JE, Goonewardena S, Ronan A, Shah D, Vasaiwala S, et al. Reappraisal of the use of inferior vena cava for estimating right atrial pressure. J Am Soc Echocardiogr 2007;20:857–61. 19. Feissel M, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med 2004;30:1834–7. 20. Barbier C, Loubières Y, Schmit C, Hayon J, Ricôme JL, Jardin F, et al. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med 2004;30:1740–6. 21. Muller L, Bobbia X, Toumi M, Louart G, Molinari N, Ragonnet B, et al. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use. Crit Care 2012;16:R188. 22. Sankoff J, Zidulka A. Non-invasive method for the rapid assessment of central venous pressure: description and validation by a single examiner. West J Emerg Med 2008;9:201–5. 23. Kent A, Patil P, Davila V, Bailey JK, Jones C, Evans DC, et al. Sonographic evaluation of intravascular volume status: Can internal jugular or femoral vein collapsibility be used in the absence of IVC visualization? Ann Thorac Med 2015;10:44,9. 24. Bauman Z, Coba V, Gassner M, Amponsah D, Gallien J, Blyden D, et al. Inferior vena cava collapsibility loses correlation with internal jugular vein collapsibility during increased thoracic or intra-abdominal pressure. J Ultrasound 2015;18:343–8. 25. Jabot J, Teboul JL, Richard C, Monnet X. Passive leg raising for predicting fluid responsiveness: importance of the postural change. Intensive Care Med 2009;35:85–90. 26. Monnet X, Rienzo M, Osman D, Anguel N, Richard C, Pinsky MR, et al. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med 2006;34:1402–7. 27. Keller AS, Melamed R, Malinchoc M, John R, Tierney DM, Gajic O. Diagnostic accuracy of a simple ultrasound measurement to estimate central venous pressure in spontaneously breathing, critically ill patients. J Hosp Med 2009;4:350–5. 28. Killu K, Coba V, Huang Y, Andrezejewski T, Dulchavsky S. Internal jugular vein collapsibility index associated with hypovolemia in the intensive care unit patients. Crit Ultrasound J 2010;2:13–7. 29. Guarracino F, Ferro B, Forfori F, Bertini P, Magliacano L, Pinsky MR. Jugular vein distensibility predicts fluid responsiveness in septic patients. Crit Care 2014;18:647. 30. Lanspa MJ, Grissom CK, Hirshberg EL, Jones JP, Brown SM. Applying dynamic parameters to predict hemodynamic response to volume expansion in spontaneously breathing patients with septic shock: reply. Shock 2013;39:462. 31. MacIntyre NR. Respiratory function during pressure support ventilation. Chest 1986;89:677–83. 32. Kimura BJ, Dalugdugan R, Gilcrease GW 3rd, Phan JN, Showalter BK, Wolfson T. The effect of breathing manner on inferior vena caval diameter. Eur J Echocardiogr 2011;12:120–3.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Internal juguler ven kollabsibilite indeksinin sepsisteki değeri Dr. Murat Haliloğlu, Dr. Beliz Bilgili, Dr. Alper Kararmaz, Dr. İsmail Cinel Marmara Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İstanbul

AMAÇ: Septik hastalarda sıvı yanıtını tahmin etmek için volüm durumunun hızlı, doğru ve tekrarlanabilir olarak değerlendirilmesi çok önemlidir. Spontan soluyan septik hastalarda sıvı yanıtının tahmininde inferiyor vena kava kollapsibilite indeksine (IVC-CI) ek olarak internal jugular ven kollapsibilite indeksinin (IJV-CI) etkinliğini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Sonografik inceleme üç aşamada gerçekleştirildi. USCOM (Ultrasonic Cardiac Output Monitor) sistemiyle hemodinamik verilerle birlikte IVC-CI ve IJV-CI ölçümleri birinci aşamada yarı oturur pozisyonda, ikinci aşamada pasif bacak kaldırma sonrasında (PBK) ve üçüncü aşamada yeniden yarı oturur pozisyona getirildikten sonra ölçüldü. Sıvı yanıtı PBK sonrası kardiyak indeksdeki (CI) değişiklikle değerlendirildi. Hastalar retrospektif olarak iki gruba ayrıldı: PBK sonrası ΔCI ≥%15 olanlar sıvı yanıtlı (R), ΔCI <%15 sıvı yanıtsız olarak kabul edildi. BULGULAR: Mekanik ventilatör desteği almayan 44 sepsis tanılı hastada (ortalama yaş 54.6±16.1 yıl) toplam 132 çift IVK ve IJV kollabsibilite indeksi ölçümü yapıldı. Bu hastalardan 23’ü (%52.2) yanıt alınan (R) olarak kabul edildi. Sıvı yanıtı alınan hastaların IJV-CI ve IVC-CI değerleri sıvı yanıtsız hastalara göre daha yüksekti (p<0.001). İnternal jugular ven kollapsibilite indeksi değeri %36 yüksek olması %78 duyarlılık ve %85 özgüllük ile sıvı yanıtlılığını tahmin edebilmektedir. Venöz çap ölçümleri için gereken zaman IJV-CI (30 sn), IVC-CI (77.5 sn) karşılaştırıldığında IJV ölçüm süresi anlamlı olarak kısa bulundu (p<0.001). TARTIŞMA: Mekanik ventilasyon desteği almayan septik hastalarda sıvı yanıtının tahmininde IJV-CI kolay uygulanabilen, invaziv olmayan bir parametredir, IVC-CI yerine kullanılabilir. Anahtar sözcükler: İnferiyor vena cava; internal juguler ven; kollabsibilite indeksi; sıvı yanıtı. Ulus Travma Acil Cerrahi Derg 2017;23(4):294–300

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doi: 10.5505/tjtes.2016.04832

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ORIGIN A L A R T IC L E

Prognostic factors in acute mesenteric ischemia and evaluation with Mannheim Peritonitis Index and platelet-to-lymphocyte ratio Eyüp Murat Yılmaz, M.D., Erdem Barış Cartı, M.D. Department of General Surgery, Adnan Menderes University Faculty of Medicine, Aydın-Turkey

ABSTRACT BACKGROUND: Acute mesenteric ischemia (AMI) is a disease that has a very high mortality rate and for which the diagnosis is frequently delayed. The aim of the present study was to assess the predictive value of the Mannheim Peritonitis Index (MPI) and platelet-to-lymphocyte (P/L) ratio in the prognosis of AMI. METHODS: The files of 34 patients diagnosed with AMI between September 2014 and April 2016 were retrospectively examined. The patients were divided into 2 groups based on survival. The parameters of MPI and P/L ratio, demographic data, and duration of hospitalization were recorded and compared. RESULTS: In all, 19 (55.9%) patients were male, and 15 (44.1%) were female. Total of 19 patients (55.9%) were discharged with a complete recovery, while 15 (44.1%) died. MPI mean value was 21.13±7.55 and 16.00±5.24 in those who died and survived, respectively (p=0.026). P/L ratio was 288.48±233.01 and 373.82±389.62 in those who survived and died, respectively (p=0.045). CONCLUSION: MPI and P/L ratio are simple and reliable methods to predict the prognosis of AMI. Keywords: Mannheim Peritonitis Index; mesenteric ischemia; platelet/lymphocyte ratio.

INTRODUCTION Acute mesenteric ischemia (AMI) is a clinical condition with a mortality rate as high as 70%, despite diagnosis and treatment.[1] This condition is seen in 1% to 2% of patients admitted with abdominal pain, though it becomes more common with increasing age, and incidence may be up to 18% in individuals aged 65 years or more.[2] The primary causes of such a high mortality rate are thought to be delayed diagnosis and various comorbid diseases seen in the elderly. While many blood analyses, such as lactate dehydrogenase, transaminases, D-dimer, D-lactate, and creatinine phosphokinase have been suggested for diagnosis of AMI, as yet, none is sufficiently specific or sensitive.[3] Diagnosis can usually be made based Address for correspondence: Eyüp Murat Yılmaz, M.D. Adnan Menderes Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 09100 Aydın, Turkey Tel: +90 256 - 212 18 50 E-mail: drmyilmaz80@gmail.com Submitted: 12.10.2016 Accepted: 06.12.2016

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on computerized tomography (CT) and mesenteric CT angiography.[4] However, the mortality rate remains high, despite surgical intervention following diagnosis.[1] The Mannheim Peritonitis Index (MPI) is a special scoring system of parameters such as age; gender; duration, severity, and extent of peritonitis; presence of malignancy; and organ failure.[5–7] Scoring systems such as the Peritonitis Index of Altona and the Acute Physiologic Assessment and Chronic Health Evaluation can also be used for peritonitis.[6,7] Several studies have demonstrated the importance of these scoring systems in cases of peritonitis due to causes such as diverticulitis or colonic perforation. However, studies investigating the predictive value of these indices for peritonitis that develops due to conditions such as bacterial translocation, necrosis, or perforation in AMI, are limited in the literature.[8] The platelet-to-lymphocyte (P/L) ratio has been recognized in recent studies as a marker that, interestingly, can predict mortality in many inflammatory events, ranging from coronary artery disease to malignancy.[9,10] While many studies have been conducted using the parameter of mean platelet volume (MPV) in AMI, the number of studies demonstrating the importance of P/L as a marker in prognosis is very limited. However, these studies have reported that high P/L value was associated with increased mortality.[10] 301

Yılmaz et al. Prognostic factors in acute mesenteric ischemia and evaluation with Mannheim Peritonitis Index and platelet-to-lymphocyte ratio

Table 1. Mannheim Peritonitis Index Risk factor

Weightage, if any

survived. Data regarding the duration of hospitalization, time from admission until operation, type of operation performed, and demographic details were recorded and statistically compared.

Age >50 years

Female genders

Statistical Analysis

Organ failures

Descriptive statistics of continuous variables are provided as mean±SD and frequency (percent). The variables were assessed after prerequisites of normality and homogeneity of variance were evaluated (Shapiro-Wilk and Levene’s tests). Independent t-test for 2 samples (Student’s t-test) was performed, and Mann Whitney U-test was used when prerequisites were not met. For comparisons of 3 or more groups, one-way analysis of variance and the Tukey honest significant difference test were utilized. When the prerequisites were not met for those groups, Kruskal-Wallis test and Bonferroni-Dunn multiple comparison tests were used. The relationships between categorical variables were analyzed using Fisher’s exact test and chi-square test. When the expected frequencies were less than 20%, an assessment using the Monte Carlo simulation was performed to include these frequencies in the analysis. Significance level was expressed as α=0.05 and α=0.01. Data were assessed using the SPSS Statistics for Windows, Version 17.0 (SPSS, Inc., Chicago, IL, USA) software package.

Malignancy 4 Preoperative duration of peritonitis

>24 hours Origin of sepsis not colonic

Diffuse generalised peritonitis

Exudates Clear 0 6

Cloudy, purulent

Faecal 12

The aim of the present study was to investigate the predictive value of MPI together with P/L ratio, a hematological marker, with respect to prognosis in patients with AMI.

MATERIALS AND METHODS The files of patients with diagnosis of AMI who had been operated on by the general surgery clinic of Adnan Menderes University Faculty of Medicine between September 2014 and April 2016 were retrospectively investigated and included in this study. A review was performed using the MPI (Table 1), and patients with missing data were excluded. The patients were divided into 2 groups: those who died and those who

RESULTS A total of 34 patients diagnosed with AMI were included in the study. Of those patients, 19 (55.9%) were male, and 15 (44.1%) were female. In all, 19 patients (55.9%) were discharged with a complete recovery, while 15 (44.1%) died. Mean age was 70.6±14.07 years and 64.63±15.54 years in

Table 2. Comparison of MPI and P/L ratios and durations Patients

Mean

Standard Deviation

Standard Error Mean

Survived

64.63

15.54

3.56

Died

70.60

14.07

3.63

Survived

16.00

5.24

1.20

Died

21.13

7.55

1.95

Survived

288.48

223.01

89.39

Died

373.82

389.02

57.58

Survived

1.11

0.74

0.17

Died

0.80

0.94

0.24

Survived

11.05

10.03

2.30

Died

8.40

9.05

2.34

Age 0.255

Mannheim score 0.026*

P/L ratio 0.045*

Time to laparotomy (hours) 0.296

Duration of hospitalization (days) 0.43

p<0.05. MPI: Mannheim peritonitis index; P/L: Platelet-to-lymphocyte.

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those who died and survived, respectively. Mean MPI value was 21.13±7.55 and 16.00±5.24 in those who died and survived, respectively (p=0.026). P/L ratio was 288.48±233.01 and 373.82±389.62 in those who survived and died, respectively (p=0.045). When the 2 groups were compared regarding length of time from admission to operation (hours) and duration of hospitalization (days), no statistically significant differences were found (p=0.43) (Table 2). Six (17.6%) of the patients had undergone exploratory laparotomy and only 1 of them could be kept alive, with administration of anticoagulant therapy; in the remaining 5 cases, no intervention could be performed due to total small intestinal necrosis. Eleven (32.4%) cases had undergone segmental small intestine resection and anastomosis, while 10 (29.4%) cases had undergone segmental small intestine resection, but ileostomy was preferred in order to avoid risk to anastomosis. Two (5.9%) patients had undergone subtotal small intestine resection, 2 (5.9%) patients had undergone segmental small intestine resection and right colectomy, 1 (2.9%) patient had undergone embolectomy, and 2 (5.9%) had undergone other procedures. When the 2 groups (those who died and

those who survived) were compared with respect to surgical intervention, a significant survival advantage was observed in the groups who had undergone segmental small intestine resection and segmental small intestine resection with ileostomy compared with other groups (p=0.03) (Table 3). When the relationship of type of surgery and MPI score was analyzed, the exploratory laparotomy group had the highest score, while the embolectomy group had the lowest score (p=0.001). Regarding P/L ratio, no statistically significant difference was found between groups based on surgical intervention (p=0.594).

DISCUSSION AMI is a condition characterized by intestinal infarction, and is more often seen in the elderly and those with atherosclerotic disease.[1] It is not very common, but demonstrates significantly high mortality, and requires immediate diagnosis and therapeutic intervention.[11] Early diagnosis is difficult; however, delayed diagnosis increases mortality. Therefore, several studies have been and are currently being conducted to better predict mortality and aid in prognosis for this condition.

Table 3. Surgical methods

Died Survived

Total

Died

Gender Female

47.4

40.0

44.1

0.667

Male

n 10 9 19

52.6

60.0

55.9

Surgery Ex lap

n 1 5 6 0.03*

Segmental small intestine resection

n %

5.3 8 42.1

33.3 3 20.0

17.6 11 32.4

Embolectomy

n 0 1 1

Subtotal small intestine resection

Segmental small intestine resection + right colectomy

Segmental small intestine resection + ileostomy

n % n % n %

0.0 1 5.3 1 5.3 7 36.8

6.7 1 6.7 1 6.7 3 20.0

2.9 2 5.9 2 5.9 10 29.4

Other (Segmental small intestine resection and segmental small

intestine resection + ileostomy)

5.3

6.7

5.9

Total

n 19 15 34

100.0

p<0.05.

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The MPI scoring system takes patient age, gender, presence of organ failure or malignancy, and parameters such as onset and extensiveness of peritonitis into consideration in determination of risk.[7] Studies have generally estimated that in peritonitis case to which a score between 21 and 29 was assigned, the mortality rate would be as high as 65%.[12] Some studies have predicted a mortality rate above 80% for peritonitis cases with MPI score above 29.[13] In our study, mean MPI value was 16.00±5.24 in those who survived, while value of 21.13±7.55 was found in those who died, and the difference was statistically significant. Krylov et al.[14] suggested in their study that mortality rate was lower and that a less radical surgical option may be appropriate in patient groups with MPI value of ≤21, while mortality rate was higher and radical surgery should be performed in groups with a value of ≥21. Sharma et al.[15] reported that MPI was a very good predictor of mortality and that its prognosis for patients with peritonitis could be relied upon. While there is a very limited number of studies evaluating the relationship between AMI and MPI, a study conducted by Yıldırım et al.[16] of 46 patients with AMI reported that patients with MPI of ≥26 had a higher mortality rate, and that the use of this index on initial admission would contribute to prognosis. Since our study also found that patients with MPI value of ≥21 had a statistically significantly higher mortality rate, we recommend that this index be used during the initial admission evaluation of patients presenting to emergency departments with AMI and that it can be used reliably to estimate prognosis. P/L ratio has been studied in many inflammatory events, ranging from coronary artery disease to malignancies, and its value in prediction of prognosis has been well demonstrated.[9,10] A study conducted by Kahramanca et al.[17] reported that P/L ratio was a good marker to estimate prognosis and debridement of Fournier’s gangrene. It has also been shown to be an important marker for malignancy, and a study conducted by Stotz et al.[18] reported that elevated P/L value was a negative factor regarding curative resection in gastrointestinal stromal tumor. Since embolism and thrombosis associated with infarction are seen in AMI, it is thought that platelets might not be innocent within this pathogenetic process and studies have been conducted to investigate their potential role.[19] Many studies have examined the association between MPV and mesenteric ischemia, and MPV has been reported to have value in the determination of prognosis.[20] Studies of P/L ratio, however, are limited in the literature. A study conducted by Toptas et al.[10] reported that elevated P/L ratio, along with elevated levels of other hematological markers, would be an important marker in the diagnosis of AMI, as well as prediction of prognosis and mortality. Our study results included a statistically significant difference in survival according to P/L ratio. Therefore, as in other inflammatory diseases, we suggest that a prognosis in AMI may be determined reliably with P/L ratio, an inexpensive and simple test that can be analyzed within the scope of a hemogram. 304

Early diagnosis and appropriate treatment are important in AMI.[1] Treatment options include methods ranging from radiological intervention to surgical methods.[21] Early diagnosis and appropriate treatment intervention reduce mortality. Among surgical options used in the present study, the most preferred method was segmental small intestine resection. In approximately half of these cases, ileostomy was preferred, since we did not consider the anastomosis line to be safe. Embolectomy could be performed in only 1 case after the diagnosis had been made under appropriate conditions and at the proper time. When we compared the P/L ratio of cases, we found no statistical differences with respect to surgical method. Therefore, we think that this marker is important only in determining prognosis and does not contribute to the selection of surgical method or the subsequent process. Exploratory laparotomy cases had the highest MPI score, while the embolectomy case had the lowest, and this was statistically significant. In almost all of the exploratory laparotomy cases, the diagnosis was delayed, near total necrosis was observed during laparotomy, and the patients died before intervention could be performed. The embolectomy case, on the other hand, was a rare case in which early diagnosis and intervention were performed, and no peritonitis had developed. We think that the difference originates here, and therefore suggest that diagnosis be made as soon as possible, followed by the most appropriate intervention. In conclusion, P/L ratio, which is reliable and simple to obtain, can be used together with MPI upon admission, and may help the surgeon and emergency physician predict prognosis in individuals thought to have AMI, an uncommon but highmortality disease. No financial support was received for this study. Conflict of interest: None declared.

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tive study evaluating utility of Mannheim peritonitis index in predicting prognosis of perforation peritonitis. J Nat Sci Biol Med 2015;6(Suppl 1):49–52. 16. Yıldırım D, Hut A, Tatar C, Dönmez T, Akıncı M, Toptaş M. Acute mesenteric ischemiade prognostik faktörler.Ulusal Cerrahi Derg 2016. 17. Kahramanca Ş, Kaya O, Özgehan G, İrkem B, Dural İ, Küçükpınar T, et al. Fournier gangreninde debridman sayısını öngörmede nötrofil lenfosit oranı ve trombosit lenfosit oranı Fournier gangreni şiddet indeksi kadar etkili midir? Ulus Travma Acil Cerrahi Derg 2014;20:107–12. 18. Stotz M, Liegl-Atzwanger B, Posch F, Mrsic E, Thalhammer M, Stojakovic T, et al. Blood-Based Biomarkers Are Associated with Disease Recurrence and Survival in Gastrointestinal Stroma Tumor Patients after Surgical Resection. PLoS One. 2016;25:11. 19. Budak YU, Polat M, Huysal K. The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency nontraumatic abdominal surgery: a systematic review. Biochem Med (Zagreb) 2016;26:178–93. 20. Türkoğlu A, Gül M, Oğuz A, Bozdağ Z, Ülger BV, Yılmaz A, et al. Mean platelet volume: is it a predictive parameter in diagnosis of acute mesenteric ischemia? Int Surg 2015;100:962–5. 21. Alemanno G, Somigli R, Prosperi P, Bergamini C, Maltinti G, Giordano A, et al. Combination of diagnostic laparoscopy and intraoperative indocyanine green fluorescence angiography for the early detection of intestinal ischemia not detectable at CT scan. Int J Surg Case Rep 2016;26:77– 80.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut mezenter iskemide prognostik faktörler ve Mannheim peritonit indeksi ve trombosit/lenfosit oranı ile değerlendirilmesi Dr. Eyüp Murat Yılmaz, Dr. Erdem Barış Cartı Adnan Menderes Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Aydın

AMAÇ: Akut mezenter iskemi (AMİ), tanısı geç konan ve mortalitesi oldukça yüksek bir hastalıktır. Mannheim peritonit indeksi (MPİ) ve trombosit/ lenfosit (T/L) oranının akut mezenter iskeminin prognozu üzerine etkisini araştırmak. GEREÇ VE YÖNTEM: Akut mezenter iskemi tanısı konan 34 hastanın dosyaları, Eylül 2014–Nisan 2016 tarihleri arasında geriye dönük olarak tarandı. Hastalar hayatını kaybeden ve kaybetmeyen diye iki gruba ayrıldı. Hastaların MPİ ve T/L oranları, demografik verileri, yatış süreleri kaydedilip karşılaştırıldı. BULGULAR: Hastaların 19’u erkek (%55.9), 15’i kadın (%44.1) olarak saptandı. Toplam 15 hasta hayatını kaybederken (%44.1),19 hasta (%55.9) sağlıklı taburcu edildi. Mannheim periton indekslerine bakıldığında ise hayatını kaybeden hastalarda ortalama değer 21.13±7.55 bulunurken, hayatını kaybetmeyen hastalarda 16.00±5.24 olarak saptandı (p=0.026). Trombosit/lenfosit oranlarına bakıldığında hayatını kaybetmeyen grupta 288.48±233.01 saptanırken hayatını kaybeden grupta ise 373.82±389.62 olarak bulundu (p=0.045). TARTIŞMA: Akut mezenter iskemi tablosunda, prognozu ön görmede MPİ ve T/L oranları basit ve güvenilir yöntemlerdir. Anahtar sözcükler: Mannheim peritonit indeksi; mezenter iskemi; trombosit/lenfosit oranı. Ulus Travma Acil Cerrahi Derg 2017;23(4):301–305

doi: 10.5505/tjtes.2016.00701

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Esophageal button battery ingestion in children Arzu Şencan, M.D., İncinur Genişol, M.D., Münevver Hoşgör, M.D. Department of Pediatric Surgery, Dr. Behçet Uz Children’s Diseases and Surgery Training and Research Hospital, İzmir-Turkey

ABSTRACT BACKGROUND: Button battery lodged in the esophagus carries a high risk of morbidity and mortality. The purpose of this study was to present cases of patients with esophageal button battery ingestion treated at our clinic and to emphasize the importance of early diagnosis and treatment. METHODS: Records of patients admitted to our hospital for foreign body ingestion between January 2010 and May 2015 were retrospectively reviewed. Cases with button battery lodged in the esophagus were included in the study. Patient data regarding age, sex, length of time after ingestion until admission, presenting clinical symptoms, type and localization of the battery, management, and prognosis were analyzed. RESULTS: Among 1891 foreign body ingestions, 71 were localized in the esophagus, and 8 of those (11.2%) were cases of button battery ingestion. Mean age was 1.7 years. Admission was within 6 hours of ingestion in 5 cases, after 24 hours had elapsed in 2, and 1 month after ingestion in 1 case. All patients but 1 knew the history of ingestion. Prompt endoscopic removal was performed for all patients. Three patients developed esophageal stricture, which responded to dilatation. CONCLUSION: Early recognition and timely endoscopic removal is mandatory in esophageal button battery ingestion. It should be suspected in the differential diagnosis of patients with persistent respiratory and gastrointestinal symptoms. Keywords: Button battery ingestion; children; esophagus.

INTRODUCTION Ingestion of button battery is a serious problem in childhood due to the widespread use of these batteries. Button batteries are the second most frequently ingested foreign body after coins.[1] Esophageal button battery necessitates urgent removal, as they can cause major corrosive injury within hours of ingestion.[2] Batteries have a negative and a positive terminal.[3] The negative terminal of the battery is made of zinc or lithium and the positive terminal is made of lithium, manganese, manganese dioxide, oxygen, silver oxide, or mercuric oxide.[4,5] When a button battery becomes lodged in the esophagus, the mucosa bridges the positive and negative ends, thus completing Address for correspondence: Arzu Şencan, M.D. Dr. Behçet Uz Çocuk Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Çocuk Cerrahisi Anabilim Dalı, İzmir Tel: +90 232 - 441 60 00 E-mail: arzusencan71@yahoo.com.tr Submitted: 21.04.2016 Accepted: 06.12.2016

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a circuit and allowing current to flow, which results in the generation of hydroxide radicals. Lithium batteries provide a higher voltage and have a longer charge than other batteries. [6] Therefore, they are more commonly used in many households. Major complications, such as perforation, mucosal burn, or fistula, are encountered more often after ingestion of lithium batteries.[4] The aim of this study was to present cases of patients with esophageal button battery ingestion who were treated at our institution and to emphasize the importance of early diagnosis and treatment.

MATERIALS AND METHODS Records of patients who were admitted to our hospital for foreign body ingestion between January 2010 and May 2015 were retrospectively reviewed. Patients with esophageal button battery ingestion were included in the study. Data regarding age, sex, length of time since ingestion until admission, presenting clinical signs and symptoms, type, size, and localization of the battery, management, and follow-up findings were analyzed.

RESULTS A total of 1891 patients were admitted to our hospital for inUlus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Ĺ&#x17E;encan et al. Esophageal button battery ingestion in children

gested foreign body in the gastrointestinal system during the study period. Among those, 71 patients had foreign body localized in the esophagus. In 8 of the 71 patients (11.2%), button battery was lodged in the esophagus. Six patients were female (75%), 2 patients were male (25%). Mean age of the patients was 1.7 years (range: 6 months-3 years). Time of admission was within 6 hours after ingestion of button battery in 5 patients, 24 hours or more in 2 patients, and 1 month in 1 patient. The presenting clinical symptoms were dysphagia, coughing, vomiting, hypersalivation, fever, poor appetite, and recurrent pulmonary infection. All of the patients knew the history of battery ingestion, with exception of the patient who was admitted 1 month after ingestion. When the history of that child was questioned more in detail, it was learned that he had been playing with the television remote control device with his 6-year-old sister about a month prior. The patient then had persistent upper respiratory symptoms and a poor appetite for a month. He had been treated by another clinician, but without any X-ray imaging, and there had been no response to treatment. The patient was referred to our institution for further treatment. Chest X-ray image revealed battery lodged in the first physiological narrowing, which is the upper esophageal sphincter, in 4 patients, and in the second physiological narrowing at the level of the aortic arch in the other 4 patients (Fig. 1). Emergent endoscopy was performed under general anesthesia for every patient. The batteries were removed with rigid esophagoscopy and foreign body forceps in 5 patients. Flexible esophagoscope and basket forceps were used for the removal of the battery in 2 patients. The battery was covered by granulation tissue in the patient who was admitted 1 month after ingestion, and both rigid and flexible esophago-

Figure 2. Grade 3a mucosal injury.

scopes were ultimately used in very difficult removal of the battery. According to Zargar classification[7] used to evaluate mucosal injury, 2 patients in the study had grade 3a and 4 patients had grade 3b mucosal injury, whereas there was no injury (grade 0) in the other 2 (Fig. 2). The 2 patients with grade 0 injury score were admitted within 6 hours after ingestion. One of the patients with grade 3a injury was also admitted within 6 hours, and the remaining patient in that category was admitted 24 hours after ingestion. Of the 4 patients with grade 3b injury, 2 were admitted within 6 hours, 1 after 24 hours had passed, and the other was the patient admitted 1 month after ingestion of the battery. One patient with grade 3a and 1 patient with grade 3b mucosal injury developed esophageal stricture 1 month after ingestion, which responded to 1 dilatation procedure. The patient admitted 1 month after ingestion, and who had grade 3b mucosal injury, also developed esophageal stricture 3 weeks after ingestion. Dilatation was performed total of 8 times with intervals of 3 weeks. All patients continued follow-up with no symptoms. Patient characteristics are summarized in Table 1.

DISCUSSION Foreign body ingestion is a common problem in the pediatric age group. The majority of cases, 75%, occur before 4 years of age.[8] Button battery ingestion makes up less than 2% of all foreign bodies ingested.[9] The incidence of button battery ingestion is about 10 cases per milllion people each year.[10] This low incidence has increased, however, with the widespread use of button batteries in the household.[11â&#x20AC;&#x201C;13] Button batteries range in size from 6 to 25 mm in diameter. Batteries larger than 12 mm are more likely to become lodged in the esophagus of young children. All of the batteries presented in this study were 20 mm in diameter. Figure 1. Button battery observed in the first narrowing of the esophagus.

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Table 1. Patient characteristics Age Sex Admission Symptom Localization Management time

Mucosal injury

1 year

Grade 3b Dilatationx1

Female

6 hours

Dysphagia+

First narrowing

Rigid esophagoscope

Follow-up

hypersalivation 1 y ear

Male

6 hours

Hypersalivation

3 years

Female

6 hours

Coughing+fever

3 years

Female

6 hours

Dysphagia

6 hours

Dysphagia+vomiting

6 months 1 year

Male Female

24 hours

3 years

Male

24 hours

1 year

Male

1 month Coughing+ poor appetite+

Dysphagia+coughing

Second narrowing Flexible esophagoscope Grade 3a Second narrowing

Grade 3b

Normal

Second narrowing Flexible esophagoscope Grade 0

Normal

First narrowing

Rigid esophagoscope

Grade 0

Normal

First narrowing

Rigid esophagoscope

Grade 3a

Normal

Second narrowing

Rigid esophagoscope

Grade 3b Dilatationx1

First narrowing

Rigid + flexible

Grade 3b Dilatationx8

recurrent lung infection

can cause mucosal ulceration, corrosive injury, and perforation, if the duration of impaction is long enough. The esophagus is the most uppermost part of the gastrointestinal tract. The severity of esophageal damage depends on the size and the electrical charge of the battery and the length of time that the battery is lodged in the esophagus.[14â&#x20AC;&#x201C;16] Damage to the esophageal mucosa starts within 2 hours after ingestion of a battery.[5,17,18] As the duration of exposure increases, the mucosa becomes edematous, and the battery can fuse to the mucosa, leading to ulceration and perforation.[16â&#x20AC;&#x201C;19] Denney et al. reported that foreign bodies localized in the same site for more than 24 hours were more likely to cause mucosal ulceration compared with those that remained less than 24 hours (46% vs 23%).[20] In the present study, both of the patients with normal endoscopic findings were among those who were admitted within 6 hours. However, severe injury may occur even in cases with early diagnosis.[21] In this study, 1 of the patients who was admitted within 6 hours after ingestion had grade 3a injury, and 2 other patients also admitted within 6 hours had grade 3b mucosal injury. Button batteries can cause mucosal injury in the esophagus through several mechanisms. These include electrical discharge, leakage of battery contents, and pressure necrosis. [4,5,11] The charge state of the button battery is an important factor in the development of mucosal injury. However, even discharged batteries have the potential to cause tissue damage, as they have enough voltage to generate external electrolytic current.[22] The seal of the battery dissolves in the acidic environment of the esophagus. This leads to the leakage of alkaline solutions (sodium or potassium hydroxide) from the battery.[17,23,24] In an in vitro study, it was demonstrated that the amount of erosion was directly correlated with the charge of the battery.[24] When these alkaline solutions react with the protein in the mucosal surface of the esophagus, it leads to lique308

Rigid esophagoscope

Normal

esophagoscope

faction necrosis, which is the main characteristic of caustic esophageal injury in children.[25] Another potential mechanism of injury following button battery ingestion is the absorption of heavy metals, such as lithium or mercury, which are released from the fragmented battery. However, mercury or lithium toxicity after battery ingestion is very rare.[9] If the lodged battery remains in the same site within the esophagus for a long time, it can cause inflammation and ischemia due to pressure necrosis.[2,11,25] Therefore, prompt removal is important to prevent damage. Many patients may be largely asymptomatic, but may present with symptoms of cough, vomiting, fever, chest pain, diarrhea, epigastric, or abdominal pain after ingestion of button battery. [3,5,9,26] If there is esophageal perforation or tracheo-esophageal fistula, symptoms may include refusal of oral intake, drooling, hematemesis, and respiratory distress.[21] All of the patients in this study presented with some of the mentioned symptoms. Presence of recurrent lung infection or coughing despite medical therapy should raise the suspicion of esophageal foreign body, even if there is no history of ingestion. Anteroposterior chest X-ray demonstrates button battery with a halo sign and step-off sign on lateral X-ray. The double-ring shadow helps to differentiate battery from coin ingestion. No chest X-ray had been obtained for the patient in this study who was admitted 1 month after ingestion of button battery. If the clinician had raised the suspicion of battery ingestion, since the patient had not responded to medical therapy and continued to have respiratory symptoms, the patient would not have developed such severe esophageal mucosal injury and his symptoms would not have persisted for so long. Button battery impacted in the esophagus requires emergent endoscopic removal under general anesthesia with endotraUlus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Şencan et al. Esophageal button battery ingestion in children

cheal intubation to protect the airway during the removal procedure. Flexible endoscopy may not be successful if adhesion of the battery to the esophageal mucosa is dense; rigid esophagoscopy may be necessary.[27] In this study, flexible esophagoscopy was performed in the removal of the battey in patients who were admitted within 6 hours after ingestion, and rigid esophagoscope was used for the patient who was admitted 1 month after ingestion. Vocal cord paralysis, esophageal perforation, and tracheoesophageal fistula with erosion into the aorta or other arteries are rare complications that may occur in patints with severe mucosal injury at the time of battery removal. [28,29] Stricture formation is another risk in mild to moderate esophageal injury. Dysphagia can occur weeks, or even years, after ingestion. Dilatation of the esophagus is helpful in the treatment of swallowing problems. In conclusion, button battery ingestion is a serious condition with high risk of life-threatening complications in childhood. Early diagnosis and immediate endoscopic removal may prevent these complications. The history of ingestion is not always available. Therefore, clinicicans must raise the suspicion of battery ingestion in patients with persistant respiratory or gastrointestinal symptoms, and chest X-ray should be obtained if symptoms persist despite medical therapy. Prevention of button battery ingestion is, of course, the best management of all. Therefore, parents and caretakers should be aware of the dangers of button battery ingestion and the importance of prompt care. Batteries should be kept out of reach of children and battery compartments of household pruducts should be more securely designed. Once ingested, urgent endoscopic removal is the best treatment to reduce the risk of morbidity and mortality. Conflict of interest: None declared.

REFERENCES 1. Arana A, Hauser B, Hachimi-Idrissi S, Vandenplas Y. Management of ingested foreign bodies in childhood and review of the literature. Eur J Pediatr 2001;160:468–72. 2. Samad L, Ali Mi Rami H. Button battery ingestion: Hazards of esophageal impaction. J Pediatr Surg 1999;34:1527–31. 3. Millar AJ, Rode H, Cywes S, Van Der Walt F. Button-battery ingestion-a hazard of modern living. S Afr Med J 1985;68:868–71. 4. Litovitz T, Whitaker N, Clark L, White NC, Marsolek M. Emerging battery-ingestion hazard: clinical implications. Pediatrics 2010;125:1168– 77. 5. Thompson N, Lowe-Ponsford F, Mant TG, Volans GN. Button battery ingestion: a review. Adverse Drug React Acute Poisoning Rev 1990;9:157–80. 6. Kramer RE, Lerner DG, Lin T, Manfredi M, Shah M, Stephen TC, et al. Management of ingested foreign bodies in children: a clinical report of the NASPGHAN Endoscopy Committee. J Pediatr Gastroenterol Nutr 2015;60:562–74.

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7. Cheng HT, Cheng CL, Lin CH, Tang JH, Chu YY, Liu NJ, et al. Caustic ingestion in adults: the role of endoscopic classification in predicting outcome. BMC Gastroenterol 2008;8:31. 8. McNeill MB, Sperry SL, Crockett SD, Miller CB, Shaheen NJ, Dellon ES. Epidemiology and management of oesophageal coin impaction in children. Dig Liver Dis 2012;44:482–6. 9. Litovitz T, Schmitz BF. Ingestion of cylindrical and button batteries: an analysis of 2382 cases. Pediatrics 1992;89:747–57. 10. Cheng W, Tam PK. Foreign-body ingestion in children: experience with 1,265 cases. J Pediatr Surg 1999;34:1472–6. 11. Litovitz TL. Battery ingestions: product accessibility and clinical course. Pediatrics 1985;75:469–76. 12. Mofenson HC, Greensher J, Caraccio TR, Danoff R. Ingestion of small flat disc batteries. Ann Emerg Med 1983;12:88–90. 13. Sharpe SJ, Rochette LM, Smith GA. Pediatric battery-related emergency department visits in the United States, 1990-2009. Pediatrics 2012;129:1111–7. 14. Sigalet D, Lees G. Tracheoesophageal injury secondary to disc battery ingestion. J Pediatr Surg 1988;23:996–8. 15. Rumack BH, Rumack CM. Disk battery ingestion. JAMA 1983;249:2509–11. 16. Temple DM, McNeese MC. Hazards of battery ingestion. Pediatrics 1983;71:100–3. 17. Bass DH, Millar AJ. Mercury absorption following button battery ingestion. J Pediatr Surg 1992;27:1541–2. 18. Kuhns DW, Dire DJ. Button battery ingestions. Ann Emerg Med 1989;18:293–300. 19. Maves MD, Carithers JS, Birck HG. Esophageal burns secondary to disc battery ingestion. Ann Otol Rhinol Laryngol 1984;93:364–9. 20. Denney W, Ahmad N, Dillard B, Nowicki MJ. Children will eat the strangest things: a 10-year retrospective analysis of foreign body and caustic ingestions from a single academic center.Pediatr Emerg Care 2012;28:731–4. 21. Fuentes S, Cano I, Benavent MI, Gómez A. Severe esophageal injuries caused by accidental button battery ingestion in children. J Emerg Trauma Shock 2014;7:316–21. 22. Jatana KR, Litovitz T, Reilly JS, Koltai PJ, Rider G, Jacobs. Pediatric button battery injuries: 2013 task force update. Int J Pediatr Otorhinolaryngol 2013;77:1392–9. 23. Rebhandl W, Steffan I, Schramel P, Puig S, Paya K, Schwanzer E, et al. Release of toxic metals from button batteries retained in the stomach: An in vitro study. J Pediatr Surg 2002;37:87–92. 24. Litovitz T, Butterfield AB, Holloway RR, Marion LI. Button battery ingestion: assessment of therapeutic modalities and battery discharge state. J Pediatr 1984;105:868–73. 25. Kost KM, Shapiro RS. Button battery ingestion: a case report and review of the literature. J Otolaryngol 1987;16:252–7. 26. Litovitz TL. Button battery ingestions. A review of 56 cases. JAMA 1983;249:2495–500. 27. Leinwand K, Brumbaugh DE, Kramer RE. Button battery ingestion in children: A paradigm for management of severe pediatric foreign body ingestions.Gastrointest Endosc Clin N Am 2016;26:99–118. 28. Brumbaugh DE, Colson SB, Sandoval JA, Karrer FM, Bealer JF, Litovitz T, et al. Management of button battery-induced hemorrhage in children. J Pediatr Gastroenterol Nutr 2011;52:585–9. 29. Gordon AC, Gough MH. Oesophageal perforation after button battery ingestion. Ann R Coll Surg Engl 1993;75:362–4.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Çocuklarda özofagus yerleşimli disk pil yutmaları Dr. Arzu Şencan, Dr. İncinur Genişol, Dr. Münevver Hoşgör Dr. Behçet Uz Çocuk Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Çocuk Cerrahisi Anabilim Dalı, İzmir

AMAÇ: Özofagusta takılı kalan disk piller yüksek morbidite ve mortalite riskine sahiptir. Bu çalışmada, kliniğimizde özofagus yerleşimli disk pil nedeniyle tedavi edilen hastalar sunuldu, erken tanı ve tedavinin önemi vurgulandı. GEREÇ VE YÖNTEM: Ocak 2010–Mayıs 2015 tarihleri arasında yabancı cisim yutma nedeniyle başvuran hastalar geriye dönük olarak incelendi. Özofagusta takılı kalan piller çalışmaya dahil edildi. Hastalar yaş, cinsiyet, başvuru süresi, başvuru semptomları, pilin yerleşim ve boyutu, uygulanan tedavi ve seyir açısından incelendi. BULGULAR: Yabancı cisim yutma ile başvuran 1891 olgunun 71’inde yabancı cisim özofagusta yerleşimliydi. Yetmiş bir özefageal yabancı cismin sekizi disk pildi (%11.2). Ortalama yaş 1.7 yıl idi. Başvuru süresi beş olguda ilk altı saat, iki olguda 24 saat sonra, bir olguda bir ay sonra idi. Bir hasta dışında hastaların tümünde yabancı cisim yutma öyküsü vardı. Tüm hastalarda pil endoskopik yolla çıkartıldı. Üç hastada dilatasyonlara yanıt veren özofageal striktür gelişti. TARTIŞMA: Özofagusta takılı kalan disk piller acil olarak tanınıp çıkartılmalıdır. Uzun süren solunum ve gastrointestinal sistem semptomları olan hastaların ayırıcı tanısında özofageal yerleşimli disk pil akılda tutulmalıdır. Anahtar sözcükler: Çocuk; disk pil yutma; özofagus. Ulus Travma Acil Cerrahi Derg 2017;23(4):306–310

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doi: 10.5505/tjtes.2016.72177

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Eight years of clinical experience with digit replantation: Demographic characteristics and outcomes Melike Oruç, M.D.,1 Koray Gürsoy, M.D.,1 Kadri Özer, M.D.,2 Özlem Çolak, M.D.,3 Yüksel Kankaya, M.D.,1 Nezih Sungur, M.D.,1 Gürhan Mustafa Ulusoy, M.D.,4 Uğur Koçer, M.D.1 1

Department of Plastic, Reconstructive and Aesthetic Surgery, Ankara Training and Research Hospital, Ankara-Turkey

Department of Plastic, Reconstructive and Aesthetic Surgery, Aydın State Hospital, Aydın-Turkey

Department of Plastic, Reconstructive and Aesthetic Surgery, Okmeydanı Training and Research Hospital, İstanbul-Turkey

Private Practice, Ankara-Turkey

ABSTRACT BACKGROUND: Despite surgical and technical advances in microsurgery, it is still difficult to obtain satisfactory results after replantation of finger amputation. The aim of the present study was to discuss some of the many factors that can affect the success rate of replantation. METHODS: A retrospective analysis of 60 patients with 85 finger replantations was performed. Revascularizations and replantations proximal to the metacarpophalangeal joint were excluded. Demographic characteristics of the patients, place of injury, mechanism of injury, level of amputation, and success rate were examined. RESULTS: A total of 53 male and 7 female patients with mean age of 31 years were included in the study. Index finger (27%) was the most commonly replanted digit. Left side was the more affected, with 62%. Mechanism of injury was crush in 56%, guillotine in 23%, and avulsion in 21% of replanted digits. Success rate was 81%, 53%, and 36% in guillotine, crush, and avulsion injuries, respectively. CONCLUSION: In conclusion, the injury type and personal variables are very important in the rate of replantation success. Knowledge about the effects of different factors on the results of replantation surgery will provide guidance to hand surgeons in order to inform patients and their relatives properly. Keywords: Amputation; finger; microsurgery; replantation.

INTRODUCTION Although finger amputation does not threaten life, it can cause serious functional and psychological problems. Tamai and Komatsu performed the first successful replantation in 1965, and the operation is now widely performed throughout the world.[1] In the literature, there are many reports about the success rate of replantation. Success can be affected by many factors, such as the level of injury, experience of the surgeon, mechanism of injury, age, gender, smoking addiction, Address for correspondence: Melike Oruç, M.D. Ankara Eğitim ve Araştırma Hastanesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Kliniği, Ulucanlar, 06340 Ankara, Turkey Tel: +90 312 - 595 36 51 E-mail: droruc@yahoo.com Submitted: 03.06.2016 Accepted: 08.11.2016

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and ischemia time.[2–6] There are generally accepted indications for replantation in the literature. In addition, the decision on replantation may also be influenced by improvements in microvascular techniques, patient preferences, technical capacity, and surgeon preferences.[7,8] The aim of this study was to report the success rate of finger replantation surgery at our center and to discuss factors that can affect successful results and the replantation decision.

MATERIALS AND METHODS A retrospective review of cases of digital replantation performed between January 2006 and December 2013 was conducted with the approval of the ethics committee of Ankara Training and Research Hospital. Traumatic total finger amputations were included in the study; subtotal amputations and any amputation proximal to the metacarpophalangeal joint were excluded. In our clinic, patient preference is accepted as a strong indication in the decision to perform replantation. With the exception of cases that can be considered to have 311

Oruç et al. Eight years of clinical experience with digit replantation: Demographic characteristics and outcomes

an absolute contraindication for surgery, such as presence of severe systemic illness, amputations at multiple levels, and severe crush injuries, if surgery is only relatively contraindicated, according to the patient’s desire, we favor surgery if we think that the finger is replantable. The medical records of all the patients, including emergency department consultations, operative reports, and outpatient summaries, were reviewed. Demographic patient data of age, sex, hand dominance, and place of injury were also recorded. Mechanism (guillotine, crush, or avulsion),[8] level of injury (according to the Tamai classification as described by Yoshimura)[9] of the involved digit, and length of hospitalization were also determined. Injuries were classified as severe if they fulfilled one of the following criteria stated by Vilkki and Göransson: amputation of the thumb through or proximal to the interphalangeal joint, or amputation of 2 or more fingers through the proximal interphalangeal joint. Survival of the replanted digit, which was defined as digit viability for a minimum of 21 days, was used for the assessment of final outcome.[10] Statistical analysis of groups was performed using SPSS for Windows, Version 15.0 (SPSS, Inc., Chicago, IL, USA) statistical software, with the level of significance set at p<0.05.

RESULTS A total of 85 digit replantations were performed in 60 patients with complete medical records. Of those, 53 were male and 7 were female. The average age of the patients was 31 years, ranging from 1 to 72 years. Seven patients (12%) were younger than 13 years of age. The left side was more often affected, with occurrence in 53 of the patients (62%). The index finger was the most commonly replanted digit at 27% of the total, followed by the middle finger at 21%, and ring finger and thumb replantations represented 20% and 19%, respectively. The least commonly replanted digit was the little finger, with 13%. The mechanism of injury was crush in 56%, guillotine (sharp) in 23%, and avulsion in 21% of replanted digits (Fig. 1). In all,

49% of the replantations were performed following amputation through or distal to Tamai level III (Fig. 2). Eleven patients underwent multiple-digit replantation and 49 underwent single-digit replantation. The thumb was replanted in 14 of the single-digit cases. A total of 18 patients (30%) were classified as having severe injuries, according to the criteria stated by Vilkki and Göransson. The lowest digit survival rate was found in patients older than 60 years of age, with a rate of 20%. In patients younger than 13 years of age, the survival rate was found to be 31%, whereas in the age group between 13 and 60 years, it was 55% (p>0.05) (Table 1). Subgroups of the patients according to gender and where the injury occurred were also examined and revealed that 71% of the replantations were performed for work-related injuries. In the age group between 13 and 60 years of age, 88% of male amputations were due to workrelated injuries received at an industrial site, and 100% of female amputations were due to injuries that occurred at home (p<0.05). Of work-related replantations, 77% were diagnosed as crush and avulsion injuries (p>0.05). Nearly all of the patients were transferred to our hospital by an emergency medical care team, so we can say that transfer conditions were quite good. In the hospital, amputated parts were preserved in physiological saline solution-soaked sponges in sterile bags and stored in containers at 4°C. Mean time from injury to surgery was 7 hours, ranging from 3 to 14 hours (Table 1). Since the transfer of the patients was typically performed by a medical care team, we believe that the warm ischemia time was not very long. Although there are no clear data, it was estimated that warm ischemia time was not more than 30 minutes, followed by cold ischemia until surgery. In cases with ischemia time of more than 10 hours, digit survival rate decreased to 37%, whereas when ischemia time was less than 6 hours, mean survival rate was 73% (Table 1) (p>0.05). It is not possible to provide precise data about the effect of transfer conditions on survival rate in this study, since transfer ZONE I NUMBER I

III

Index Finger-Little Finger

Thumb

ZONE I NUMBER V

Figure 1. Percentage of replantations by mechanism and success rate for each mechanism.

312

–

III

Figure 2. Number of replantations by Tamai level.

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Oruç et al. Eight years of clinical experience with digit replantation: Demographic characteristics and outcomes

Table 1. Associations between digit survival and variables Variable

Survived

Failed

Total

n % n % n %

Age (years) 0.108 <13

4 31 9 69 13 15

13–60

37 55 30 45 67 79

>60

1 20 4 80 5 6

Total 85 100 Sex 0.008 Male

41 55 34 45 75 88

Female

1 10 9 90 10 12

Total 85 100 Hand laterality 0.933 Left

26 49 27 51 53 62

Right

16 50 16 50 32 38

Total 85 100 Digit 0.483 Thumb

9 56 7 44 16 19

Index

8 35 15 65 23 27

Middle

10 56 8 44 18 21

Ring

8 47 9 53 17 20

Little

7 64 4 36 11 13

Total 85 100 Tamai level 0.614 I

1 100 0 0 1 1

7 47 8 53 15 18

III

15 58 11 42 26 31

10 40 15 60 25 29

9 50 9 50 18 21

Total 85 100 Mechanism of injury 0.036 Guillotine

13 81 3 19 16 23

Crush

20 53 18 47 38 56

Avulsion

5 36 9 64 14 21

Total 68 100 Time from injury to surgery (hours) <6

8 73 3 27 11 25

6–10

15 63 9 37 24 56

>10

3 37 5 63 8 19

0.287

Total 43 100

conditions were quite good. However, general medical knowledge tells us that conditions during transfer can have a direct affect on digit survival. Therefore, it is important that all members of medical transport teams and emergency units know how to preserve amputated parts properly. The mean length of hospitalization was 13 days, ranging from 2 to 32 days. Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

In total, 42 of the 85 digit replantations were successful, a success rate of 49.4%. When grouped according to type of injury, success rates were 81%, 53%, and 36% in guillotine, crush, and avulsion injuries, respectively (Fig. 1). Chi-square analysis indicated that there was a significant difference in survival rate between groups (p<0.05). 313

Oruç et al. Eight years of clinical experience with digit replantation: Demographic characteristics and outcomes

Replantation was achieved in all patients in initial surgery; operation was concluded after confirmation of sufficient arterial and venous circulation, and no amputation and stump reconstruction was performed at that time. In the ultimately unsuccessful replantation group, 8 of 43 fingers were reoperated on. Patients were taken to the operating room in mean time of 10 hours (range: 6–14 hours) after recognition of symptom of arterial or venous insufficiency on mean of third day (range: 2–5 days) following first operation. In the successful replantation group, 4 of 42 fingers were reoperated on after mean of 6 hours (range: 2–8 hours) after recognition of symptoms that can cause failure on mean of third day (range: 2–4 days). Of the 4 cases of reoperation in the successful group, the problem was determined to be arterial in 1 finger and venous in the remaining 3. The problem was arterial in 2 fingers and venous in 6 fingers for the reoperated 8 fingers in the failure group.

DISCUSSION Despite microsurgical improvements, successful replantation still depends on many factors related to the patient, environment, and culture. There are well-defined indications for replantation, such as thumb amputation, single finger amputation distal to the insertion of the flexor digitorum superficialis tendon, multiple finger amputations, and amputation at any level in children.[5,8] There are also absolute and relative contraindications for surgery. The surgeon’s way of thinking can be important in the decision when considering relative contraindications. Although the indications in the literature are well known, we believe that strong patient desire is also a factor in the replantation decision. After the elimination of definite contraindications for surgery, once the patient’s wishes are known, if we believe replantation is possible in cases that may be questionable, we recommend surgery.[11] The success rate of replantations varies greatly in the literature. There are studies from Asian countries with 85% to 100% success rate.[6,9,12] There are fewer reports about success rates from Western countries. In 2 studies from Canada and the United States, successful replantation was reported as 57% and 71%.[1,10] In our study, success rate of replantation was similar to results reported in studies from Western countries. The disparity may be related to many factors. One is that the practice of clinical microsurgery was initiated by Tamai, and while it then spread quickly to the United States, Australia, and Europe, the technical experience of surgeons in Asian countries may be greater.[8,9] Another reason for varied success rates in different reports may be related to factors regarding patient selection. For example, Waikakul et al. excluded patients with comorbid 314

injuries and those with chronic illnesses, like diabetes mellitus, from their study.[6] In that study, when a classification was performed according to injury type, the success rate was reported as 33.3% and 50.9% in crush and degloving injuries, respectively.[6] In our study, the success rate was 81% in guillotine type injuries. The rate was 53% and 36% for crush and avulsion type injuries, respectively, and these percentages are quite similar to those seen in the literature.[6,9] In addition, the age of the patient is also important and can affect the success of replantation. Although in our study, age was not significantly correlated with success rate, successful results were lower in children and the older age group than in adults (31%, 20%, and 55%, respectively). Since the vessels are narrower and the venous vessel wall is thinner in children, the technical difficulties of replantation are greater in this age group, which affects the success rate.[13,14] Also, broader indications for replantation in children and attempting replantation for almost all types of injury in this age group may also increase the number of unsuccessful cases.[15,16] Greater loss of replantation in patients of older age may be correlated with weakness of the vascular structures. One other patient-related factor that may affect results is the predisposition of the white race to thrombophilia when compared with the population of the Far East.[17] In our study, the index and middle fingers were the fingers most often affected, as in previous studies.[13,18,19] We found that gender significantly affected the success rate: unsuccessful replantations were seen in female patients more often than in male patients. A review of the literature reveals that various success rates have been reported related to gender.[3,14] Yu et al. stated in their meta-analysis of 2015 that gender did not significantly affect survival rate.[20] Difference in survival between genders may be related to technical differences among centers and differences in case features. In addition, women have relatively narrower blood vessels than men, which may be a reason for a lower success rate in female patients in our study. The number of female patients was very small in the present study, and this also limits our ability to reach a conclusion about the effect of gender on success of the surgery. Our results did not indicate that the amputation level according to the Tamai classification affected achieving a successful result. Nor did ischemia time significantly affect success rate. Although a statistically significant correlation was not found between ischemia time and success rate, the ratio of loss was 27% for cases with <6 hours of ischemia, while it increased to as much as 73% for cases with >10 hours of ischemia. In the literature, successful digit replantation has been reported after extended ischemia of up to 94 hours, but these reports are very few.[21,22] Although it would seem that greater ischemia time would have a negative effect on Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Oruç et al. Eight years of clinical experience with digit replantation: Demographic characteristics and outcomes

replantation success and functional results, as in our study, a meta-analysis in the literature found that there was not a statistically significant difference between ischemia time <12 hours and >12 hours.[20] This may be related to the fact that fingers have quite a bit less muscular tissue and can therefore tolerate longer period of ischemia. However, aside from the increased ischemic tolerance of the soft tissue of the fingers, it must be kept in mind that reperfusion damage can be very harmful at the cellular level, especially for the endothelial cells of the capillaries. This condition can lead to unsuccessful replantation and unsatisfactory functional results.[22] In our study, the majority of the cases (75%) were males in the age group of 13–60 years, and most of the injuries occurred at an industrial location. In contrast, all of the female patients were injured at home. This is likely due to the fact that males in this age group are mostly of working age and their work often involves greater physical labor and risk. There were more crush type injuries than any other type in our study, which was probably related to the large number of workplace injuries. The mechanism of injury is also an important determinant in the achievement of a successful replantation. Although there is not a statistically significant difference between crush and avulsion type injuries, the failure rate after replantation attempt is significantly higher in these 2 groups compared with guillotine-type injuries.[20] Choi et al. stated that a severe crush injury can be accepted as contraindication for digital replantation.[23] Our results also revealed a significantly higher success rate in guillotine injuries compared with crush and avulsion injuries (81%, 53% and 36% respectively). The reoperation decision and its timing are also important determinants for successful results after replantation. In our study, there was not a significant correlation between time elapsed before reoperation and success rate, but of the 12 reoperated patients, the 4 who were reoperated on sooner had successful results, which may suggest that earlier decision to reoperate can be finger-saving. In conclusion, replantation is a difficult surgical procedure that requires meticulous work and an experienced team. It is clear that the success rate of replantation can be affected by many variables, from the transfer of the amputated finger to the quality of surgical equipment, and patient-related factors.

Conclusion When different variables are kept in mind, our success rate after digital replantation was found to be similar to that in the literature. At this point, we believe that as the ability of surgeons to choose suitable patients for operation and the experience of surgeons grows, success rates will increase, too. Conflict of interest: None declared.

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REFERENCES 1. Neinstein RM, Dvali LT, Le S, Anastakis DJ. Complete digital amputations undergoing replantation surgery: a 10-year retrospective study. Hand (N Y) 2012;7:263–6. 2. Beris AE, Lykissas MG, Korompilias AV, Mitsionis GI, Vekris MD, Kostas-Agnantis IP. Digit and hand replantation. Arch Orthop Trauma Surg 2010;130:1141–7. 3. Dec W. A meta-analysis of success rates for digit replantation. Tech Hand Up Extrem Surg 2006;10:124–9. 4. Janezic TF, Arnez ZM, Solinc M, Zaletel-Kragelj L. One hundred sixtyseven thumb replantations and revascularisations: early microvascular results. Microsurgery 1996;17:259–63. 5. Soucacos PN. Indications and selection for digital amputation and replantation. J Hand Surg Br 2001;26:572–81. 6. Waikakul S, Sakkarnkosol S, Vanadurongwan V, Un-nanuntana A. Results of 1018 digital replantations in 552 patients. Injury 2000;31:33–40. 7. McCabe SJ. Patient participation in the decision for replantation. Hand Clin 2001;17:351–5. 8. Morrison WA, McCombe D. Digital replantation. Hand Clin 2007;23:1–12. 9. Yoshimura M. Indications and limits of digital replantation. JMAJ 2003;46:460–7. 10. Fufa D, Calfee R, Wall L, Zeng W, Goldfarb C. Digit replantation: experience of two U.S. academic level-I trauma centers. J Bone Joint Surg Am 2013;95:2127–34. 11. Coban YK. Finger replantation without anticoagulant therapy. Edorium J Plast Cosmet Surg 2014;1:1–4. 12. Fukui A, Tamai S. Present status of replantation in Japan. Microsurgery 1994;15:842–7. 13. Li J, Guo Z, Zhu Q, Lei W, Han Y, Li M, et al. Fingertip replantation: determinants of survival. Plast Reconstr Surg 2008;122:833–9. 14. Hamilton RB, O’Brien BM, Morrison A, MacLeod AM. Survival factors in replantation and revascularization of the amputated thumb--10 years experience. Scand J Plast Reconstr Surg 1984;18:163–73. 15. Kim JY, Brown RJ, Jones NF. Pediatric upper extremity replantation. Clin Plast Surg 2005;32:1–10. 16. Michalko KB, Bentz ML. Digital replantation in children. Crit Care Med 2002;30(11 Suppl):S444–7. 17. Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008;112:19–27. 18. Largo TW, Rosenman KD. Michigan work-related amputations, 2008. J Occup Environ Med 2013;55:280–5. 19. Kim WK, Lim JH, Han SK. Fingertip replantations: clinical evaluation of 135 digits. Plast Reconstr Surg 1996;98:470–6. 20. Yu H, Wei L, Liang B, Hou S, Wang J, Yang Y. Nonsurgical factors of digital replantation and survival rate: A metaanalysis. Indian J Orthop 2015;49:265–71. 21. Wei FC, Chang YL, Chen HC, Chuang CC. Three successful digital replantations in a patient after 84, 86, and 94 hours of cold ischemia time. Plast Reconstr Surg 1988;82:346–50. 22. Lin CH, Aydyn N, Lin YT, Hsu CT, Lin CH, Yeh JT. Hand and finger replantation after protracted ischemia (more than 24 hours). Ann Plast Surg 2010;64:286–90. 23. Choi MS, Lee JH, Ki SH, Ahn HC. Trends in digital replantation. Curr Orthop Pract 2012;23:284–8.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Parmak replantasyonları ile ilgili sekiz yıllık klinik deneyim: Demografik özellikler ve sonuçlar Dr. Melike Oruç,1 Dr. Koray Gürsoy,1 Dr. Kadri Özer,2 Dr. Özlem Çolak,3 Dr. Yüksel Kankaya,1 Dr. Nezih Sungur,1 Dr. Gürhan Mustafa Ulusoy,4 Dr. Uğur Koçer1 Ankara Eğitim ve Araştırma Hastanesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Kliniği, Ankara Aydın Devlet Hastanesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Kliniği, Aydın Okmeydanı Eğitim ve Araştırma Hastanesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Kliniği, İstanbul 4 Özel Muayenehane, Ankara 1 2 3

AMAÇ: Mikrocerrahideki cerrahi ve teknik ilerlemelere rağmen halen parmak amputasyonlarının replantasyonu sonrasında tatminkar sonuçlar elde etmek zordur ve başarı oranlarını belirleyen birçok faktör mevcuttur. Bu yazıda, replantasyonun başarısını değiştirebilecek faktörleri tartışmak amaçlandı. GEREÇ VE YÖNTEM: Altmış hastada uygulanan 85 parmak replantasyonunun geriye dönük analizi yapıldı. Revaskülarizasyonlar ve metakarpofalangeal eklemin proksimalindeki replantasyonlar çalışma dışı bırakıldı. Hastaların demografik özellikleri, yaralanma yeri, yaralanma mekanizması, amputasyon seviyesi ve başarı oranları değerlendirildi. BULGULAR: Ortalama yaşları 31 olan 53 erkek ve yedi kadın hasta çalışmaya dahil edildi. İşaret parmağı en sık replante edilen parmaktı (%27). Sol el en sık etkilenen taraftı (%62). Yaralanma mekanizması, replante edilen parmakların %56’sında ezilme, %23’ünde giyotin tip, %21’inde ise avülziyondu. Başarı oranları giyotin, ezilme ve avülziyon tipi yaralanmalarda sırasıyla %81, %53 ve %36 olarak bulundu. TARTIŞMA: Sonuç olarak, replantasyonların başarı oranlarını belirlemede yaralanma tipi ve kişisel değişkenler oldukça önemlidir. Replantasyon cerrahisinin sonuçlarına etki edebilecek değişkenler hakkında bilgi sahibi olmak, hasta ve yakınlarını doğru bilgilendirme konusunda el cerrahlarının yanında acil cerrahi hizmeti veren hekimler için de oldukça yönlendirici olacaktır. Anahtar sözcükler: Amputasyon; mikrocerrahi; parmak; replantasyon. Ulus Travma Acil Cerrahi Derg 2017;23(4):311–316

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doi: 10.5505/tjtes.2016.40040

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ORIGIN A L A R T IC L E

Ischemia-modified albumin and other inflammatory markers in the diagnosis of appendicitis in children Selçuk Nazik, M.D.,1 Veli Avci, M.D.,2 Zeynep Küskü Kiraz, M.D.3 1

Department of Infectious Diseases and Clinical Microbiology, Bingöl Maternity and Children’s Hospital, Bingöl-Turkey

Department of Pediatric Surgery, Bingöl Maternity and Children’s Hospital, Bingöl-Turkey

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

ABSTRACT BACKGROUND: The aim of the present study was to determine relationship of ischemia-modified albumin (IMA) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) to appendicitis in children. METHODS: Study included total of 63 patients who presented at hospital between May 2015 and November 2015. Of these, 30 were cases of appendicitis, and 33 were healthy control subjects. The groups were statistically similar in age and gender. RESULTS: Receiver operating characteristic curve was evaluated for IMA, CRP, ESR, WBC, MPV, NLR, and PLR values in patients with appendicitis, and IMA was determined to have highest area under the curve value (0.991), followed by NLR (0.946), CRP (0.808), PLR (0.779), ESR (0.767), WBC (0.749), and MPV (0.583). CONCLUSION: Use of NLR, PLR, IMA, and ESR values may be helpful in diagnosis of appendicitis, in addition to WBC and CRP values, lower right quadrant abdominal pain, and ultrasonography signs commonly used. Keywords: Appendicitis; inflammatory markers; ischemia-modified albumin.

INTRODUCTION Appendicitis is a common cause of emergent surgical intervention in children. Obstruction of the appendix lumen is the most important factor in the etiology of appendicitis. [1] Blockage, for example with mucus, leads to swelling and increased pressure within the lumen and the walls of the appendix. This pressure results in thrombosis and occlusion of the small vessels, and stasis of lymphatic flow. As occlusion of blood vessels progresses, the appendix becomes ischemic, and then necrotic.[2,3] Lifetime incidence of appendicitis is 7%. Rate of mortality is less than 1% in the general population; however, this rate increases to as much as 50% in advanced Address for correspondence: Selçuk Nazik, M.D. Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fak. Enfeksiyon Hast. ve Klinik Mikrobiyoloji Anabilim Dalı, Kahramanmaraş, Turkey Tel: +90 344 - 300 34 34 E-mail: dr.selcuknazik@hotmail.com Submitted: 13.02.2016 Accepted: 01.11.2016

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age groups. Diagnosis of appendicitis has been made based on lower right quadrant abdominal pain and increased number of leukocytes, but sensitivity of these signs is low. Measures such as Alvarado score, neutrophil-to-lymphocyte ratio (NLR), number of white blood cells (WBC), and C-reactive protein (CRP) level have also been used in the diagnosis of appendicitis. Nevertheless, rate of false positivity in diagnosis is still approximately 15%.[4–6] Level of biomarker ischemiamodified albumin (IMA) increases secondary to ischemia of the myocardium and skeletal muscle, and can be measured using albumin-cobalt binding test.[7,8] Complete blood count (CBC) is an easily available and inexpensive test. WBC, neutrophil and lymphocyte counts, and value of mean platelet volume (MPV) are evaluated in CBC test. These values and ratios, such as NLR and platelet-to-lymphocyte ratio (PLR) are commonly used as inflammatory markers. The aim of the present study was to determine relationship between appendicitis and markers of CRP, erythrocyte sedimentation rate (ESR), WBC, NLR, PLR, MPV, and IMA.

MATERIALS AND METHODS The study included a total of 63 patients who presented at 317

Nazik et al. Ischemia-modified albumin and other inflammatory markers in the diagnosis of appendicitis in children

hospital between May 2015 and November 2015. Of these, 30 were cases of appendicitis in patients below 18 years of age, and 33 were healthy control subjects. Groups were similar in age and gender distribution. The ethics committee of the Bingöl General Secretariat of the Association of Public Hospitals approved the study. Families of the participants were informed about the study, and provided written consent. Appendicitis cases were evaluated in 2 groups: acute appendicitis (AA) and perforated appendicitis (PA). Age, gender, and laboratory analysis values were recorded for patient and control groups. CBC, CRP, and ESR were analyzed using Beckman Coulter LH 750, Beckman Coulter Immage 800 (Beckman Coulter, Inc., Brea, CA, USA) and Linear analyzer (Linear Chemicals, S.L., Montgat, Spain), according to the guidelines of the manufacturers.

Analysis of Ischemia-Modified Albumin Serum IMA values were analyzed using principle of albumincobalt binding defined by Bar-Or et al. using Mindray BS-2000 auto analyzer (Mindray Medical International Ltd., Shenzhen, China).[7] According to this method, 100 μL of cobalt dichloride reagent was added to 35 μL of serum and incubated for 5 minutes. During this incubation period, cobalt [Co(II)] binds to the N-terminal of unmodified albumin. When 50 μL of dithiothreitol (DTT) reagent is added, DTT combines with unbound Co(II), and results in color development. Color change of the sample was evaluated at 470 nm, and values were measured in absorbance units (AbsU).

Statistical Analysis Study data were evaluated using SPSS Statistics for Windows, Version 17.0 statistical software (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean±SD, and categorical variables were expressed in numbers and percent values. Student’s t-test was used to compare continuous variables between independent groups. For categorical variables, chi-square test was used to compare independent groups. Receiver operating characteristic (ROC)

curve was used to evaluate the power of markers to predict appendicitis. The following major criteria were used in ROC analysis to define best predicting test: value of sensitivity 100%, value of false positivity as zero (1-specificity=0), area under the curve (AUC) of 1, and diagnostic value of AUC of p<0.05. Youden’s index was used to determine cut-off value; this index reflects maximum value of sum of sensitivity and specificity, overlapping with nearest point to upper left angle in ROC graph. In evaluating accuracy of diagnostic test, sensitivity and specificity were calculated at 95% confidence interval (CI). P value <0.05 was accepted as statistically significant.

RESULTS Study included total of 63 cases. Of these, 30 (47.6%) were cases with appendicitis and 33 (52.4%) were controls. Group with appendicitis included 18 males (60%) and 12 females (40%), and control group included 23 males (69.7%) and 10 females (30.3%). There was no statistically significant difference between groups in distribution of gender (p=0.420). Mean age of patients with appendicitis and controls was 119.2±27.4 months and 105.6±30.8 months, respectively. Difference in age was not statistically significant between groups (p=0.07). Among cases with appendicitis, 27 (90%) had AA, and 3 (10%) had PA. Of cases with AA, 12 (44.4%) were younger than 120 months of age, and 15 (55.6%) were 120 months of age or older. Of the cases with PA, 1 (33.3%) was younger than 120 months of age, and 2 (66.7%) were 120 months of age or older. Values of CRP, ESR, WBC, NLR, and IMA in appendicitis and control groups are presented in Table 1. Calculations for cut-off, sensitivity, specificity, AUC, 95% CI, and p value regarding power of ESR, CRP, WBC, MPV, NLR, PLR, and IMA to predict cases with appendicitis and results are presented in Table 2.

Table 1. C-reactive protein, erythrocyte sedimentation rate, white blood cell, neutrophil lymphocyte ratio, and ischemia-modified albumin values in appendicitis and control groups

Appendicitis (n=30)

Control (n=33)

Mean±SD Mean±SD

Erythrocyte sedimentation rate (mm/h)

25.90±17.0

14.84±8.0

0.002

C-reactive protein (mg/dL)

29.63±41.3

7.45±9.2

0.007

White blood cell (103/µL)

12.12±4.8

7.73±2.1 0.000

Mean platelet volume (fL)

8.23±0.8

8.08±0.9

0.501

Neutrophil lymphocyte ratio

6.06±4.1

1.24±0.8

0.000

164.23±77.3

103.42±34.6

0.000

0.56±0.1

0.33±0.1

0.000

Platelet lymphocyte ratio Ischemia-modified albumin (AbsU) *

Groups were compared using Student’s t-test. SD: Standard deviation.

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Table 2. Cut-off, sensitivity, specificity, area under curve, 95% confidence interval, and p values regarding power of ESR, CRP, WBC, MPV, NLR, PLR, and IMA to predict appendicitis

Cut-off

Sensitivity %

Specificity %

Area under curve

95% CI

ESR (mm/h)

76.7

75.8

0.767

64.2–89.1

0.000

CRP (mg/dL)

5.2

73.3

0.000

WBC (103/µL) 8.87

75.8

0.808

69.2–92.4

69.7

0.749

62.1–87.8 0.001

MPV (fL)

8.15

53.3

60.6

0.583

44.1–72.6

NLR

1.77

76.7

78.8

0.946

89.8–99.5 0.000

0.256

PLR

119.64

66.7

0.779

66.7–89.1 0.000

IMA (AbsU)

0.445

96.7

99.7

0.991

97.6–100

0.000

Values in groups were calculated using receiver operating characteristic curve. CI: Confidence interval; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; WBC: White blood cell; MPV: Mean platelet volume; NLR: Neutrophil lymphocyte ratio; PLR: Platelet lymphocyte ratio.

DISCUSSION Appendicitis is one of the most common causes of emergent surgical intervention in children. Clinical presentation (pain in the lower right abdomen, defense, and rebound), fever, high WBC count and CRP level, and ultrasonography (USG) signs are used in diagnosis of the disease.[9] Patients with PA were screened in a study conducted by Gürleyik, and of the total, 69.7% were male and 30.3% were female. Among children, 70.9% of the patients were male and 29.1% were female.[10] Yıldız et al. investigated risk factors in appendicitis in children and reported that 66.3% of patients with appendicitis were male.[11] In the present study, most of the appendicitis patients were male, which was in accordance with the results in the literature. Inflammatory markers have frequently been studied as indicators of appendicitis. Of these, CRP is most investigated marker. Albu et al. evaluated level of CRP in cases of AA and reported that sensitivity and specificity were 100% and 84.6%, respectively, when cut-off value was 2.5 mg/dL.[12] In study performed by Mengücük et al., CRP level of patients with pathological diagnosis of appendicitis (focal, suppurative, or perforated) was statistically significantly higher when compared with cases that did not have pathological diagnosis of appendicitis.[13] In another study conducted by Sack et al., CRP level of group with PA and group with abdominal pain who did not undergo surgery was compared. They found that CRP was significantly higher in group with PA (p<0.001).[14] In the same study, ESR level was also higher in group with appendicitis. In the current study, CRP and ESR values were also statistically significantly higher in patients with appendicitis, compared with control subjects. Bozkurt et al. investigated WBC values in cases of appendicitis in preoperative period, and group with appendicitis had WBC level statistically significantly higher than that of control group (p=0.001).[15] Panagiotopoulou et al. found values of WBC (p<0.0001) and CRP (p<0.0001) were significantly Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

higher in patients with AA compared with normal group. In another study, WBC value was statistically significantly higher in group of children with PA (p<0.002) or suppurative appendicitis (p<0.001), compared with group with abdominal pain who did not require surgery. However, when WBC of group with early appendicitis (mucosal ulceration and focal appendicitis) was compared that of group with abdominal pain who did not require surgery, no statistically significant difference was found (p>0.05).[14] In the present study, results were similar to those reported in the literature. In study conducted by Kahramanca et al. to investigate NLR value in patients who underwent appendectomy, study groups comprised cases diagnosed as appendicitis histopathologically and those not diagnosed as appendicitis.[5] In that study, NLR value in groups with and without appendicitis was 8.10±7.0 and 5.89±5.2, respectively; this difference between groups was statistically significant (p<0.001). The following values were determined in evaluation of ROC curve drawn to reveal power of NLR to predict cases with appendicitis: cutoff: 4.68; AUC: 0.639 (p<0.001); sensitivity 65.3%; specificity 84.6%; and 95% CI, 59.1–68.7. In another study performed by Jung et al., NLR value was compared between PA and non-PA groups, and it was determined that NLR value was statistically significantly higher in PA group (p<0.001). AUC value of NLR was 0.755 (95% CI, 0.660–0.834), cut-off value was 5.6, sensitivity was 78.0%, and specificity was 65.9%.[16] In the current study, NLR value in group with appendicitis was statistically significantly higher than in control group, which was in accordance with results seen in the literature. We did not find a study that evaluated relationship between appendicitis and PLR value in search of the literature. Thus, our results in this regard may be considered the first. In the current study, PLR value was statistically significantly higher in appendicitis cases, compared with control group (p=0.000). MPV indicates size and activity of platelets, and is used as an indicator of platelet dysfunction. Increased MPV value is relat319

Nazik et al. Ischemia-modified albumin and other inflammatory markers in the diagnosis of appendicitis in children

ed to thrombotic diseases and endothelial function disorders. [17] Controversial results have been obtained in studies investigating the importance of MPV in patients with appendicitis. Yardımcı et al. reported value of MPV in cases of appendicitis and control subjects of 9.3±8 fL and 8.5±0.9 fL, respectively (p=0.0005); the authors claimed that MPV value may be helpful in clinical determination of severity of AA.[18] In another study performed by Sevinç et al., MPV value was statistically significantly lower in cases of appendicitis (8.2±1.2 fL) compared to normal appendix (8.3±1.1 fL; p=0.001). In addition, MPV was significantly lower in patients with complicated appendicitis (p=0.001).[19] Furthermore, Bozkurt et al. did not determine statistically significant difference between MPV value in cases of appendicitis and control group (p=0.478). [15] In our study, we found no relationship between MPV value and appendicitis, similar to result reported by Bozkurt et al. Free radicals formed by tissue damage cause IMA to increase within minutes and it remains high for 6 to 12 hours before returning to normal value. Free radical damage that occurs in AA increases IMA value and helps in diagnosis of appendicitis.[4,20–22] Dumlu et al. investigated markers of oxidative stress in appendicitis cases in study that included 65 patients who underwent appendectomy and 30 control subjects. Two groups were evaluated regarding IMA level, since it increases in state of ischemia, and value in preoperative cases of appendicitis and controls was 0.64±0.09 AbsU and 0.31±0.09 AbsU, respectively. Value in group with appendicitis was statistically significantly higher when compared with control group (p<0.001).[23] In the current study, IMA value was also statistically significantly higher in patients with appendicitis; IMA was found to be better parameter in prediction of cases with appendicitis than other inflammatory markers. Appendicitis is one of the most common reasons for emergent surgical intervention in children. Early diagnosis decreases rate of mortality and morbidity in cases of appendicitis, and is therefore extremely important. We conclude that use of NLR, PLR, IMA, and ESR values in diagnosis would be helpful, in addition to WBC and CRP values, lower right quadrant abdominal pain, and USG signs commonly used in diagnosis of appendicitis. Conflict of interest: None declared.

REFERENCES 1. Engin O, Calik S, Calik B, Yildirim M, Coskun G. Parasitic appendicitis from past to present in Turkey. Iran J Parasitol 2010;5:57–63. 2. Danny OJ. Acute Appendicitis and Peritonitis. In: Dennis LK, Stephen LH, Jameson JL, Dan LL, Joseph L, Anthony SF, editors. Harrison’s. 19th ed. New-York: McGraw-Hill; 2015. p. 1985–89. 3. Kadim AAM. Surgical and clinical review of acute appendicitis. International Journal of Multidisciplinary and Current Research 2016;4:280–7. 4. Kadıoğlu H, Kaptanoğlu L. The use of ischemia modified albumin in emergency surgery. J Kartal TR 2012;23:106–9.

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5. Kahramanca S, Ozgehan G, Seker D, Gökce EI, Seker G, Tunç G, et al. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2014;20:19–22. 6. Panagiotopoulou IG, Parashar D, Lin R, Antonowicz S, Wells AD, Bajwa FM, et al. The diagnostic value of white cell count, C-reactive protein and bilirubin in acute appendicitis and its complications. Ann R Coll Surg Engl 2013;95:215–21. 7. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report. J Emerg Med 2000;19:311–5. 8. Bhagavan NV, Lai EM, Rios PA, Yang J, Ortega-Lopez AM, Shinoda H, et al. Evaluation of human serum albumin cobalt binding assay for the assessment of myocardial ischemia and myocardial infarction. Clin Chem 2003;49:581–5. 9. Chan L, Shin LK, Pai RK, Jeffrey RB. Pathologic continuum of acute appendicitis: sonographic findings and clinical management implications. Ultrasound Q 2011;27:71–9. 10. Gürleyik G. Age and sex-specıfıc changes ın patıents wıth perforated appendıcıtıs. Ulusal Cerrahi Dergisi 2001;17:111–6. 11. Yıldız T, Bozdağ Z, Erkorkmaz U, Emre A, Turgut T, Ilçe Z. Analysis of risk factors for the development of pediatric appendicitis. Ulus Travma Acil Cerrahi Derg 2013;19:554–8. 12. Albu E, Miller BM, Choi Y, Lakhanpal S, Murthy RN, Gerst PH. Diagnostic value of C-reactive protein in acute appendicitis. Dis Colon Rectum 1994;37:49–51. 13. Mengücük ME, Ayten R, Bülbüller N, Gödekmerdan A, Başbuğ M, Mungan İ. Role of Creactive Protein, Procalsitonin and Neopterin in the Diagnosis of Acute Appendicitis. Fırat Tıp Dergisi 2010;15:40–3. 14. Sack U, Biereder B, Elouahidi T, Bauer K, Keller T, Tröbs RB. Diagnostic value of blood inflammatory markers for detection of acute appendicitis in children. BMC Surg 2006;6:15. 15. Bozkurt S, Köse A, Erdogan S, Bozali GI, Ayrik C, Arpaci RB, et al. MPV and other inflammatory markers in diagnosing acute appendicitis. J Pak Med Assoc 2015;65:637–41. 16. Jung SK, Rhee DY, Lee WJ, Woo SH, Seol SH, Kim DH, et al. Neutrophil-to-lymphocyte count ratio is associated with perforated appendicitis in elderly patients of emergency department. Aging Clin Exp Res 2016. 17. Vagdatli E, Gounari E, Lazaridou E, Katsibourlia E, Tsikopoulou F, Labrianou I. Platelet distribution width: a simple, practical and specific marker of activation of coagulation. Hippokratia 2010;14:28–32. 18. Yardımcı S, Uğurlu MÜ, Coşkun M, Attaallah W, Yeğen ŞC. Nötrofillenfosit oranı ve ortalama trombosit hacminin akut apandisitin şiddetini belirlemedeki rolü. Ulus Travma Acil Cerrahi Derg 2016;22:163–8. 19. Sevinç MM, Kınacı E, Çakar E, Bayrak S, Özakay A, Aren A, et al. Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. Ulus Travma Acil Cerrahi Derg 2016;22:155–62. 20. Søreide K. The role of high-mobility group box-1 (HMGB-1) in the management of suspected acute appendicitis: useful diagnostic biomarker or just another blind alley? Scand J Trauma Resusc Emerg Med 2011;19:28. 21. Kalan M, Talbot D, Cunliffe WJ, Rich AJ. Evaluation of the modified Alvarado score in the diagnosis of acute appendicitis: a prospective study. Ann R Coll Surg Engl 1994;76:418–9. 22. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. 23. Dumlu EG, Tokaç M, Bozkurt B, Yildirim MB, Ergin M, Yalçin A, et al. Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis. Clinics (Sao Paulo) 2014;69:677–82.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İskemi modifiye albümin ve diğer enflamatuvar belirteçlerin çocuk apandisit tanısındaki yeri Dr. Selçuk Nazik,1 Dr. Veli Avci,2 Dr. Zeynep Küskü Kiraz3 1 2 3

Bingöl Kadın Doğum ve Çocuk Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Kliniği, Bingöl Bingöl Kadın Doğum ve Çocuk Hastanesi, Çocuk Cerrahi Kliniği, Bingöl Osmangazi Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Eskişehir

AMAÇ: Bu çalışmada çocuklardaki apandisit ile iskemi modifiye albümin (İMA), C-reaktif protein (CRP), eritrosit sedimentasyon hızı (ESR), beyaz küre sayısı (WBC), nötrofil lenfosit oranı (NLR), platelet lenfosit oranı (PLR) ve ortalama platelet hacmi (MPV) arasındaki ilişkinin ortaya konulması amaçlandı. GEREÇ VE YÖNTEM: Çalışmaya Mayıs 2015 ve Kasım 2015 tarihleri arasında hastanemize başvuran toplam 63 olgu dahil edildi, bunların 30’u apandisit olgusu ve 33’ü sağlıklı kontrol olgu idi. Gruplar yaş ve cinsiyet açısından benzerdi. BULGULAR: Apandisitli hastalarda İMA, CRP, ESR, WBC, MPV, NLR ve PLR değerlerinin ölçüldüğü ROC eğrisinin değerlendirilmesinde, en yüksek eğri altında kalan alan (EAA) İMA’da (EAA: 0.991) tespit edilirken, onu takip eden EAA değerleri NLR (EAA: 0.946), CRP (EAA: 0.808), PLR (EAA: 0.779), ESR (EAA: 0.767), WBC (EAA: 0.749) ve MPV (EAA: 0.583) idi. TARTIŞMA: Bu amaçla apandisit tanısında sıkça kullanılan yüksek WBC ve CRP düzeyi, sağ alt kadran ağrısı ve USG sonuçlarına ek olarak NLR, PLR, İMA ve ESR değerlerinin de tanıda kullanılmasının faydalı olacağı kanaatindeyiz. Anahtar sözcükler: Apandisit; enflamatuvar belirteçler; İMA. Ulus Travma Acil Cerrahi Derg 2017;23(4):317–321

doi: 10.5505/tjtes.2016.11823

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ORIGIN A L A R T IC L E

Damage control surgery: 6 years of experience at a level I trauma center Amit Gupta, M.D., Subodh Kumar, M.D., Sushma Sagar, M.D., Pawan Sharma, M.D., Biplab Mishra, M.D., Maneesh Singhal, M.D., Mahesh C Misra, M.D. Division of Trauma Surgery & Critical Care, J P N Apex Trauma Center, All India Institute of Medical Sciences, New Delhi-India

ABSTRACT BACKGROUND: Damage control surgery (DCS) has been a well-established practice in the management of trauma victims for more than 2 decades now. The primary aim of this study was to review and analyze the presentation and outcome of patients with torso trauma who underwent DCS at Level I trauma center. METHODS: Retrospective study was conducted using database records prospectively maintained over period of 6 years from 2008 through 2013 at an urban Level I trauma center. Data available from hospital medical records were analyzed to study presentation, mechanism of injury, organs injured, associated injuries, and outcome in patients who underwent DCS following torso trauma. Primary outcome measure was survival. RESULTS: Total of 61 patients were identified who had undergone DCS during the study period. Majority of these patients were males (n=59), had sustained blunt trauma as result of road traffic injury, and had presented with shock (n=49). The 30-day mortality rate was 54%. Mortality was significantly associated with shock (63% cases died; p=0.008), and with Glasgow Coma scale ≤8 (85% died; p=0.001). Injuries significantly associated with high mortality were hepatic injury (n=15; 11 died), major vascular injury (n=10; 3 died), cardiac injury (n=5; 3 died), and pelvic fracture (n=17; 10 died). Re-exploration was required in 28 cases with 13 deaths. Mesh laparostomy was performed in 24 cases, with mortality in 58%. CONCLUSION: In the absence of more effective alternative, especially at facilities with limited resources, DCS may be appropriate in critically injured patients; however, it continues to be associated with significant morbidity and high mortality, even at tertiary care centers. Keywords: Damage control surgery; emergency surgery; lethal triad; torso trauma; trauma.

INTRODUCTION The concept of damage control approach is a paradigm shift from definitive repair of all injuries to focused hemorrhage control, containing contamination, and deferring definitive repair for a later stage at an appropriate time after initial stabilization of the physiological parameters.[1,2] This change has increased survival rate after major trauma to over 50%.[3–5] The term “damage control” was defined by Rotondo et al.[6] Address for correspondence: Subodh Kumar, M.D. Division of Trauma Surgery & Critical Care, J P N Apex Trauma Center, All India Institute of Medical Sciences 110029 New Delhi, India Tel: +91-11-26731070 E-mail: subodh6@gmail.com Submitted: 04.10.2015 Accepted: 16.06.2016

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in 1993 as “initial control of hemorrhage and contamination followed by intra-peritoneal packing and rapid closure, resuscitation continued in the intensive care unit (ICU), followed by re-exploration for definitive repair.” These represent the first stage, namely the decision to perform DCS, and the final stage of abdominal wall closure. Two further stages have been added to the 3 traditional stages of operation, restoration of physiology, and definitive surgery.[7] However, little has been documented on factors predicting mortality in DCS setting. The aim of this study was to analyze presentation and to determine factors that may predict mortality in patients undergoing damage control surgery (DCS). The vicious triad of death in trauma, namely hypothermia, acidosis, and coagulopathy, should be tackled by either initial abbreviated laparotomy or any other damage control procedure, correction of physiological derangements, and finally, definitive repair of all injuries at a later stage. The concept requires a dedicated team effort with careful patient selection to achieve favorable results. Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Gupta et al. Damage control surgery: 6 years of experience at a level I trauma center

MATERIALS AND METHODS Retrospective study was conducted using prospectively maintained database records of 61 consecutive patients with torso trauma who underwent various DCS procedures at JPN Apex Trauma Centre, All India Institutes of Medical Sciences, New Delhi, India, over a period of 6 years from January 2008 through December 2013. Data of patientâ&#x20AC;&#x2122;s age, gender, mode of injury, presence of shock at presentation, Focused Assessment by Sonography in Trauma (FAST) report, Glasgow Coma Score status, organ(s) injured, DCS procedure performed, type of closure, frequency of re-exploration, length of intensive care unit (ICU) stay, length of ventilator support, outcome, and if the patient died, cause and time of death, were collected from hospital medical records and recorded. All patients of all age groups who presented with organspecific injuries or polytrauma following blunt or penetrating trauma, and who required immediate surgery for hemorrhage control or to contain contamination were included in the study. Patients who died in the emergency department (ED) during resuscitation or during surgery were excluded. Blood and blood products were transfused in patients who presented with features suggestive of class III or class IV hemorrhagic shock. For refractory cases, massive transfusion protocol was activated with transfusion ratio of packed red blood cells, fresh frozen plasma, and platelet concentrate of 1:1:1.

Table 1. Details of damage control procedures Procedure Frequency Perihepatic packing

Splenectomy 19 13

Pelvic packing

Thoracotomy 8 External pelvic fixation

Major vessel ligation

Nephrectomy 3 Bowel stapling/ligation

Bowel stomas

External fixation of long bones

Laparostomy 24 Post packing therapeutic/ prophylactic angioembolization 7

Table 2. Mode of injury Mode of injury

Injured

Survivors

Road traffic crash

Fall from height

Railway track injury

DCS was performed in patients with lethal triad of coagulopathy, acidosis, and hypothermia.

Gunshot wound

Assault

6 4

Operative Procedure

Mechanism unknown

Total

61 38

Exploratory laparotomy was performed using midline incision. Perihepatic packing, splenectomy, and pelvic packing were most common procedures performed to achieve hemostasis (Table 1). In most patients, exteriorization of bowel was done to prevent contamination in presence of bowel injuries (Table 1). Bilateral anterolateral thoracotomy was performed in 5 patients with cardiac injury using clamshell incision. Cardiac chamber injuries were repaired using polypropylene sutures.

operation room (OR) was 45 minutes. Forty-nine patients were in state of hemorrhagic shock at presentation, and of these, 41 were FAST positive and 38 were non-responders. Polytrauma was seen in 54 patients.

All statistical calculations, including chi-square analysis and unpaired t-tests, were performed using SPSS Statistics for Windows, Version 17.0. (SSPS Inc., Chicago, IL, USA); p value <0.05 was considered statistically significant.

RESULTS Total of 2025 emergency trauma surgeries were performed during the study period and 61 (3%) of these surgeries were DCS for torso trauma. Majority of the patients were males (n=59), and the predominant mechanism of injury was blunt trauma, seen in 54 cases. Among the various modes of injury, motor vehicle crashes were responsible for causing injuries in half of these patients (Table 2). Average delay in presentation to ED was 2 hours, and average disposition time from ED to Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Figure 1. Thoracoabdominal injury managed with tube thoracostomy and perihepatic packing.

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Table 3. Frequency of injured organs Injured organ

Frequency

Liver 15 Spleen 19 Major intra-abdominal vessel

Pelvic fracture

Genito urinary

Chest 21 Cardiac 05 Bowel/mesenteric 06 Long bone fractures

Retroperitoneal hematoma

Spine 05

Table 4. Primary damage control procedures and techniques of abdominal closure Serial Primary damage control procedure(s) No

n=61

Mesh laparostomy

Splenectomy with primary abdominal closure

Thoracotomy and primary closure

External pelvic fixation

External fixation of long bones

Nephrectomy with primary abdominal closure

Major abdominal and limb vessel ligation

with primary abdominal closure

Total

Maxillofacial 03 Morel lavallee

Pancreatoduodenal 02 Traumatic brain injury (TBI)

Liver and spleen were the 2 most frequently injured organs requiring DCS (Table 3) and hence, perihepatic packing (Figure 1) and splenectomy were the 2 most frequently performed DCS procedures (Table 1). There were 5 patients with cardiac injuries who were managed with thoracotomy and repair of cardiac chamber injury. Sixteen patients with pelvic fractures were managed either with pelvic packing (13 cases) or external pelvic fixators (3 cases). Mesh laparostomy was performed in 24 patients who had undergone perihepatic packing, pelvic packing, significant bowel contamination, or bowel edema, to mini-

mize occurrence of abdominal compartment syndrome (ACS) (Table 4). Average blood requirement during first 24 hours was 4 units. Post packing prophylactic angio-embolization was performed in 5 cases after hemodynamic stabilization in ICU. All the patients were monitored in ICU postoperatively and re-explorations were carried out after 48 to 72 hours. Twenty-eight cases were re-explored; 8 of them were re-explored twice and 1 case was re-explored 3 times. None of the patients developed ACS postoperatively. Average number of ventilator days, ICU stay, and hospital stay were 7 days (range: 1–30 days), 9 days (range: 4–37 days), and 14 days (range: 9–45 days) respectively. Average injury severity score (ISS) was 28.3 (range: 16–75), and average New ISS (NISS) was 34.1 (range: 16–75). Twenty-eight patients were alive at the end of 1 month. Major-

Table 5. Relationship between organ damage, physiological status, and mortality rate Serial No

Organ(s) damaged

Shock Y/N

Mortality rate (n=33) n %

Liver alone

3.2

Spleen alone

4.9

Pelvis alone

4.9

Head, lungs, liver

9.8

Liver, spleen, mesentery, portal vein, pelvis

4.9

Head, heart, long bones

4.9

Head, long bones, face

3.2

Head, kidneys, mesentery, bowel

6.5

Pancreaticoduodenal, head, maxilla, spine, long bones

3.2

Head, soft tissues, pelvis

3.2

Pelvis, retroperitoneum, IVC, head

1.6

Lungs, mesentery, liver, spleen, IVC, retroperitoneum

3.2

Total

IVC: Inferior vena cava.

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definitive and prolonged surgeries may end up in losing the patient. We also applied DCS principles not only to all patients with abdominal trauma, but included patients with thoracoabdominal, head, pelvic, long bone, soft tissue, and vascular trauma as well. DCS was most commonly required for abdominal and pelvic trauma, which represented 75% of our cases.

Figure 2. Ligation of right hepatic artery followed by perihepatic packing done for a grade V liver trauma

ity of the remaining 33 patients died of hemorrhagic shock (Table 5). In 29 of 33 cases, mechanism of injury was blunt trauma and all were FAST positive during primary survey. Of these 33 patients, 7 died within 6 hours of arrival, 19 died within 24 hours, and the remaining 7 died after more than 24 hours. Average ISS of these 33 fatal cases was 32 and average NISS was 40. Of 49 patients who were in shock at presentation, 31 died. Mortality rate was 85% in patients who had associated severe traumatic brain injury. Of 5 cases of cardiac injury, 3 died. Mortality in 17 cases of thoraco-abdominal injuries (Figure 2) was 41%, whereas it was 59% in those with pelvic trauma. Thirteen of 28 patients who were re-explored died.

DISCUSSION Basic philosophy of DCS has evolved within the continuum of military and civilian trauma care since the Napoleonic Wars, and these techniques have firm foundation within the history of military medicine.[8] In the latter part of the 18th century, during the Napoleonic campaign, French military surgeon Jean Larrey alluded to the rationale for expedited battlefield procedures with his conclusion, “When a limb is so much injured by a gunshot wound that it cannot be saved, it should be amputated immediately. The first 24 hours is the only period during which the system remains tranquil, and we should hasten during this time, as in all dangerous diseases, to adopt the necessary remedy.”[9] Historical military references to techniques of DCS in the United States appear around the time of the Civil War.[10] The concept of “damage control” was borrowed from the United States Navy. It represents the capacity of a ship to absorb damage and maintain mission integrity.[11] In surgery, “damage control” refers to staged strategy for treatment of severe exsanguinating injuries designed to ensure patient survival. To begin with, concept of DCS was applied to abdominal trauma, but now it is also being extended to other serious and life-threatening extra-abdominal injuries in which performing Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

The concept of abdominal packing for uncontrolled hemorrhage is one of the initial damage control maneuvers described in 1908 by Pringle, the first to describe the concept of hepatic packing in patients with portal venous hemorrhage. [12] Halsted later encouraged the placement of rubber sheets between the packs and the liver to protect the liver parenchyma.[13] We packed the perihepatic space or the pelvic cavity with multiple abdominal mops with radio-opaque tracers, which were removed after achieving hemodynamic stability and correcting coagulopathy after 48 to 72 hours. In World War II, the Second Auxiliary Surgery Group treated over 22,000 combat casualties, including 8800 severely wounded, between 1943 and 1945.[14] The ensuing 912-page report and scientific publications produced after the war yielded insight into the surgical treatment of the severely wounded and the utility of techniques aimed at the correction of profound physiological derangements immediately endangering life, which is now described as damage control. In the present study, we observed that DCS principles were applied to 3% of entire emergency trauma surgeries performed during 6 years of study period. It was recognized in several case series that temporizing surgical procedures during the Vietnam War often provided a survival advantage when compared with definitive surgical therapy. [15] Several reports since the Vietnam War revalidated the concept in civilian trauma, as reported for the first time by Lucas and Ledgerwood in a prospective 5-year evaluation of 637 patients treated for liver injury.[16] Three of these patients had their liver therapeutically packed and all 3 survived. Five years later, Feliciano et al. reported 90% survival rate in 10 patients with severe liver injury treated with liver packing.[17] Stone introduced the concept of abbreviated laparotomy and intra-abdominal packing for the exsanguinating hypothermic and coagulopathic trauma patient in 1983.[18] Definitive surgical repairs were accomplished once hemodynamic stability was restored and coagulopathy corrected. This strategy resulted in survival of 11 patients out of 17 who were found to have coagulopathy. [18] Application of these techniques to trauma patients, including major vascular injuries, continued to evolve over the next several years. In our study, average ISS and NISS were found to be 28.3 and 34.1, respectively, which were suggestive of high potential for mortality and morbidity. But adopting DCS philosophy translated into survival in 46% of these patients. Potential lethal links between hypothermia and coagulopathy in trauma victims have been studied extensively.[19,20] Hypothermia, acidosis, and coagulopathy are associated with high 325

Gupta et al. Damage control surgery: 6 years of experience at a level I trauma center

mortality.[21–24] DCS is used in patients who would not survive regular surgery because of their deranged physiological state. Sharp and Locicero demonstrated that packing the abdominal cavity to prevent development of acidosis, hypothermia, and coagulopathy can be done safely.[22] We performed perihepatic packing in 15 cases and pelvic packing in 13, resulting in survival of 4 and 5 cases, respectively. Many authors have reported success with similar salvage techniques.[4,25,26] During the last decade, a number of authors have also described use of DCS in cases of thoracic, vascular, orthopedic, and neurosurgical trauma.[27–31] Rotondo and Schwab coined the term “damage control” and outlined logistics of performing 3-phased approach in 1992. [6] They reported survival rate of 77% in patients with major vascular injury and 2 or more visceral injuries. Johnson and Schwab recently introduced a fourth phase to the existing 3, and referred to it as “Damage Control Ground Zero” or DC 0.[32] It represents the earliest phase of damage control in the pre-hospital arena or ED, and focuses on injury pattern recognition and early decision to proceed with damage control.[32] It includes strategies such as minimizing pre-hospital time and abbreviated ED resuscitation that includes intubation, blood transfusion, and rapid access to the OR. Throughout damage control, they also emphasized rewarming as well as restoring red cell and plasma volume. They reported 90% survival in their damage control population, confirming the effectiveness of these strategies.[32] A recent collective review by Shapiro et al. of over 1000 damage control patients reported an overall survival rate of 50%.[33] We also observed similar survival rate (46%) in our study. Incidence of DCS among emergency surgeries varies in the literature from 8.9% to 18%.[31,34,35] In our study, 3% of emergency surgeries for trauma were DCS. A possible explanation for this difference is that most patients with severe trauma did not reach the hospital early as result of inefficient prehospital care compared with developed countries. Mortality rate for DCS has been reported in the range of 26% to 67%. [34,35] In our series, mortality rate was 54%, and most was seen during the first 24 hours after surgery. Aoki et al.[21] performed a retrospective study to identify risk factors associated with mortality in 68 patients who underwent DCS. They found overall mortality rate of 66%. Another study showed that there is a window of opportunity of 60 to 90 minutes to salvage a patient before temperature drops below 32°C.[36] Beyond this point, mortality is as high as 100% as described by Jurkovich et al.[37] We observed a statistically significant association between severe head trauma (p=0.001) and shock (p=0.008) with mortality. Other injuries that significantly contributed to mortality were hepatic injury, pelvic trauma, major vascular injury, thoraco-abdominal injury, and cardiac injury. In a recent study conducted by Talia et al., adoption of DCS principles led to significant decrease in trauma coagulopathy mortality from 46% to 19%.[38] In a nutshell, the 326

entire philosophy of DCS focuses on early control of major hemorrhage and optimization of the physiology, to be followed by staged definitive anatomical or structural repair.[39–43]

Summary The concept of damage control surgery is rapid initial control of hemorrhage and contamination with packing and temporary closure, followed by resuscitation in ICU, and subsequent re-exploration and definitive repair once normal physiology has been restored. Damage control techniques are both feasible and effective, not only on the battlefield, but also in civilian practice. This damage control paradigm challenges surgeons, especially those in resource-constrained environments, to have a low threshold to perform damage control procedures in order to mitigate the deleterious consequences of the lethal triad of trauma. The damage control philosophy is grounded in the principle that the survival of the patient is the only priority, and thus, the potential for significant morbidity must be accepted. It is better to have a live problem than a dead solution.

Compliance with Ethical Requirements Approval by an ethics committee was not applicable. Conflict of interest: None declared.

REFERENCES 1. Mattox KL. Introduction, background, and future projections of damage control surgery. Surg Clin North Am 1997;77:753–9. 2. Rotondo MF, Zonies DH. The damage control sequence and underlying logic. Surg Clin North Am 1997;77:761–77. 3. Garrison JR, Richardson JD, Hilakos AS, Spain DA, Wilson MA, Miller FB, et al. Predicting the need to pack early for severe intra-abdominal hemorrhage. J Trauma 1996;40:923–9. 4. Hirshberg A, Mattox KL. Planned reoperation for severe trauma. Ann Surg 1995;222:3–8. 5. Kouraklis G, Spirakos S, Glinavou A. Damage control surgery: an alternative approach for the management of critically injured patients. Surg Today 2002;32:195–202. 6. Rotondo MF, Schwab CW, McGonigal MD, Phillips GR 3rd, Fruchterman TM, Kauder DR, et al. ‘Damage control’: an approach for improved survival in exsanguinating penetrating abdominal injury. J Trauma 1993;35:375–83. 7. Loveland JA, Boffard KD. Damage control in the abdomen and beyond. Br J Surg 2004;91:1095–101. 8. Helling TS, McNabney WK. The role of amputation in the management of battlefield casualties: a history of two millennia. J Trauma 2000;49:930–9. 9. Larrey DJ. Memories de chirurgicales militaire et campagnes. Paris; J Smith 1817:4;516. 10. US War Department. The war of the rebellion: a compilation of the official records of the Union and Confederate Armies. Washington, DC:US Government Printing Office 1880–1901;19:106–17. 11. Department of Defense. Surface Ship Survivability. Washington, DC: Department of Defense. Naval War Publications 1996;31:3-20. 12. Pringle JH. V. Notes on the Arrest of Hepatic Hemorrhage Due to Trauma. Ann Surg 1908;48:541–9. 13. Halsted W. Ligature and suture material : the employment of fine silk in preference to catgut and the advantage of transfixing tissues and vessels in controlling hemorrhage- also an account of the introduction of gloves,

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Gupta et al. Damage control surgery: 6 years of experience at a level I trauma center gutta-percha tissue and silver foil. JAMA. 1913;LX:1119–26. 14. Brewer LA 3rd. The contributions of the Second Auxiliary Surgical Group to military surgery during World War II with special reference to thoracic surgery. Ann Surg 1983;197:318–26. 15. Jones EL, Peters AF, Gasior RM. Early management of battle casualties in Vietnam. An analysis of 1,011 consecutive cases treated at a mobile army surgical hospital. Arch Surg 1968;97:1–15. 16. Lucas CE, Ledgerwood AM. Prospective evaluation of hemostatic techniques for liver injuries. J Trauma 1976;16:442–51. 17. Feliciano DV, Mattox KL, Jordan GL Jr. Intra-abdominal packing for control of hepatic hemorrhage: a reappraisal. J Trauma 1981;21:285–90. 18. Stone HH, Strom PR, Mullins RJ. Management of the major coagulopathy with onset during laparotomy. Ann Surg 1983;197:532–5. 19. Reed RL 2nd, Bracey AW Jr, Hudson JD, Miller TA, Fischer RP. Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels. Circ Shock 1990;32:141–52. 20. Patt A, McCroskey BL, Moore EE. Hypothermia-induced coagulopathies in trauma. Surg Clin North Am 1988;68:775–85. 21. Aoki N, Wall MJ, Demsar J, Zupan B, Granchi T, Schreiber MA, et al. Predictive model for survival at the conclusion of a damage control laparotomy. Am J Surg 2000;180:540–5. 22. Sharp KW, Locicero RJ. Abdominal packing for surgically uncontrollable hemorrhage. Ann Surg 1992;215:467–75. 23. Arthurs Z, Cuadrado D, Beekley A, Grathwohl K, Perkins J, Rush R, et al. The impact of hypothermia on trauma care at the 31st combat support hospital. Am J Surg 2006;191:610–4. 24. Burch JM, Ortiz VB, Richardson RJ, Martin RR, Mattox KL, Jordan GL Jr. Abbreviated laparotomy and planned reoperation for critically injured patients. Ann Surg 1992;215:476–84. 25. Moore EE. Thomas G. Orr Memorial Lecture. Staged laparotomy for the hypothermia, acidosis, and coagulopathy syndrome. Am J Surg 1996;172:405–10. 26. Cué JI, Cryer HG, Miller FB, Richardson JD, Polk HC Jr. Packing and planned reexploration for hepatic and retroperitoneal hemorrhage: critical refinements of a useful technique. J Trauma 1990;30:1007–13. 27. Hildebrand F, Giannoudis P, Kretteck C, Pape HC. Damage control: extremities. Injury 2004;35:678–89. 28. Giannoudis PV, Pape HC. Damage control orthopaedics in unstable pel-

vic ring injuries. Injury 2004;35:671–7. 29. Rosenfeld JV. Damage control neurosurgery. Injury 2004;35:655–60. 30. Reilly PM, Rotondo MF, Carpenter JP, Sherr SA, Schwab CW. Temporary vascular continuity during damage control: intraluminal shunting for proximal superior mesenteric artery injury. J Trauma 1995;39:757–60. 31. Chovanes J, Cannon JW, Nunez TC. The evolution of damage control surgery. Surg Clin North Am 2012;92:859–75. 32. Johnson JW, Gracias VH, Schwab CW, Reilly PM, Kauder DR, Shapiro MB, et al. Evolution in damage control for exsanguinating penetrating abdominal injury. J Trauma 2001;51:261–71. 33. Shapiro MB, Jenkins DH, Schwab CW, Rotondo MF. Damage control: collective review. J Trauma 2000;49:969–78. 34. Morris JA Jr, Eddy VA, Blinman TA, Rutherford EJ, Sharp KW. The staged celiotomy for trauma. Issues in unpacking and reconstruction. Ann Surg 1993;217:576–86. 35. Nicholas JM, Rix EP, Easley KA, Feliciano DV, Cava RA, Ingram WL, et al. Changing patterns in the management of penetrating abdominal trauma: the more things change, the more they stay the same. J Trauma 2003;55:1095–110. 36. Hirshberg A, Sheffer N, Barnea O. Computer simulation of hypothermia during “damage control” laparotomy. World J Surg 1999;23:960–5. 37. Jurkovich GJ, Greiser WB, Luterman A, Curreri PW. Hypothermia in trauma victims: an ominous predictor of survival. J Trauma 1987;27:1019–24. 38. Sorrentino TA, Moore EE, Wohlauer MV, Biffl WL, Pieracci FM, Johnson JL, et al. Effect of damage control surgery on major abdominal vascular trauma. J Surg Res 2012;177:320–5. 39. Fries C A, Mark J. Trauma resuscitation and damage control surgery. Emergency Surgery 2010;28:563–67. 40. Kurian J. Mylankal, Michael G. Control of major haemorrhage and damage control surgery. Emergency Surgery 2013;31:574–81. 41. Rodrigues RR, Carmona MJ, Junior JO. Bleeding and damage control surgery. Curr Opin Anaesthesiol 2016;29:229–33. 42. Kisat M, Zafar SN, Hashmi ZG, Pardhan A, Mir T, Shah A, et al. Experience of damage control trauma laparotomy in a limited resource healthcare setting: A retrospective Cohort Study. Int J Surg 2016;28:71–6. 43. Giannoudi M, Harwood P. Damage control resuscitation: lessons learned. Eur J Trauma Emerg Surg 2016;42:273–82.

ORİJİNAL ÇALIŞMA - ÖZET

Hasar kontrol cerrahisi: Birinci seviye travma merkezinde altı yıllık deneyim Dr. Amit Gupta, Dr. Subodh Kumar, Dr. Sushma Sagar, Dr. Pawan Sharma, Dr. Biplab Mishra, Dr. Maneesh Singhal, Dr. Mahesh C Misra Travma Cerrahisi ve Kritik Hasta Bakım Bölümü, J P N Apex Travma Merkezi, Hindistan Tıp Bilimleri Enstitüsü, Yeni Delhi-Hindistan

AMAÇ: Yirmi yıldan uzun zamandan beri travmalı hastaların tedavisinde hasar kontrol cerrahisi (HKC) iyi kanıtlanmış bir uygulama olmuştur. Bu çalışmanın ana amacı, beden travması sonrası 1. seviye travma merkezinde hasar kontrol cerrahisi (HKC) geçirmiş hastaların başvuru belirtileri ve sonuçlarını gözden geçirmek ve analiz etmekti. GEREÇ VE YÖNTEM: Kentsel 1. seviye travma merkezinde 2008 ile 2013 arası altı yıllık dönem boyunca ileriye yönelik olarak muhafaza edilmiş veri tabanı ile geriye dönük bir çalışma yürütüldü. Beden travması sonrası HKC’si geçirmiş hastalarda başvuru semptomları, travmanın mekanizması, yaralanan organlar, eşlik eden yaralanmalar ve sonuçlarını incelemek için hastane tıbbi kayıtlarından elde edilen veriler analiz edildi. Birincil sonuç ölçümü sağkalım idi. BULGULAR: Çalışma dönemi boyunca HKC’si geçirmiş toplam 61 hasta tanımlandı. Bu hastaların çoğu erkek bireyler (n=59) olup trafik kazasında yaralanma sonucu künt travmaya maruz kalıp şokla (n=49) gelmişti. Otuz günlük mortalite oranı %54 idi. Mortalite şokla (olguların %63’ü hayatını kaybetmişti; p=0.008 ve ≤8 puanlık Glasgow Koma Ölçeğiyle (GKÖ) (olguların %85’i hayatını kaybetmişti: p=0.001) anlamlı derecede ilişkiliydi. Karaciğer (n=5; 11 hayatını kaybetme), majör vasküler (n=10; 3 hayatını kaybetme), kalp (n=5; 3 hayatını kaybetme) yaralanması ve pelvis kırığı (n=17, 10 hayatını kaybetme) yüksek mortalite oranlarıyla anlamlı derecede ilişkiliydi. Yirmi sekiz olguda yeniden eksplorasyon gerekti ve 13 ölüm olayı meydana geldi. Meş laparostomisi %58 mortalite oranıyla 24 olguda gerçekleştirildi. TARTIŞMA: Özellikle kaynakları kısıtlı kurumlarda kritik önemde yaralanması olan hastalarda hasar kontrol cerrahisi düşüncesi uygun olabilir. Daha etkili tedavi alternatiflerinin olmadığı üçüncü basamak merkezlerde bile önemli derecede morbidite ve yüksek derecede mortaliteyle ilişkili olmayı sürdürmektedir. Anahtar sözcükler: Acil cerrahi; beden travması; hasar kontrol cerrahisi; ölümcül üçleme; travma. Ulus Travma Acil Cerrahi Derg 2017;23(4):322–327

doi: 10.5505/tjtes.2016.03693

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ORIGIN A L A R T IC L E

Use of trauma scoring systems to determine the physician’s responsibility in cases of traumatic death with medical malpractice claim Murat Nihat Arslan, M.D.,1 Çisem Kertmen, M.D.,2 Deniz Oğuzhan Melez, M.D.,1 Durmuş Evcüman, M.D.,3 Yalçın Büyük, M.D.4 1

Morgue Department, the Council of Forensic Medicine, İstanbul-Turkey

Düzce Branch Office, the Council of Forensic Medicine, Düzce-Turkey

Çanakkale Branch Office, the Council of Forensic Medicine, Çanakkale-Turkey

The Council of Forensic Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Traumatic injury is near the top of World Health Organization list of leading causes of death, and one of the major factors affecting mortality is the severity of the trauma. During medical intervention for trauma patients, some injuries may be overlooked, and this misstep may be the basis of a malpractice claim. The objective of this study was to provide a new approach to evaluating medical malpractice cases by discussing the benefits of the use of trauma scores. METHODS: Cases of alleged malpractice that were discussed and concluded between 2010 and 2013 were selected from the case archive of the General Committee of the Council of Forensic Medicine (GC of CFM). Injury severity scores were calculated from the medical records of accused physicians and from the autopsy or final clinical evaluation records and compared. RESULTS: Between the years 2010 and 2013, 263 cases of alleged medical malpractice were discussed and concluded by the general committee. Of these, in 25 cases of patient death, the reason for admission to the hospital was traumatic injury. Various surgical specialties were involved. In these 25 cases, 34 physicians were accused of medical malpractice, and the General Committee classified the interventions of 14 physicians in 12 cases as “malpractice.” Missed injuries and unrecognized diagnoses can be established by comparing the Injury Severity Score and New Injury Severity Score values in the findings of accused physicians with the subsequent findings of last evaluation or autopsy. CONCLUSION: In a medical malpractice case, calculating injury severity scores may assist an expert witness or judge to detect any unseen injuries and to determine the likely survival potential of the patient, but these values do not provide enough information to evaluate all of the evidence or draw conclusions about the entire case. All contributing factors to trauma severity should be considered along with the trauma score and other case factors. Keywords: Injury Severity Score; medical malpractice; missed injuries; New Injury Severity Score, traumatic deaths.

INTRODUCTION In trauma cases resulting in patient death, determination of the cause of death and the causation of death with the Address for correspondence: Murat Nihat Arslan, M.D. Çobançeşme Mahallesi, Kımız Sokak., No: 1, Bahçelievler, 34196 İstanbul, Turkey Tel: +90 212 - 454 15 00 E-mail: mnarslan@yahoo.com Submitted: 24.08.2016 Accepted: 06.12.2016

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claimed intervention is important in determining any level of physician responsibility in the death (as well as responsibility of the perpetrator, in cases of trauma caused by criminal action). A finding of intercurrent death has various outcomes for both criminal and compensation law. Especially in deaths after traumatic injuries due to assault, investigation of medical malpractice claims should reveal the exact cause of death and other associated factors directly or indirectly affecting the death mechanism. Moreover, this investigation should be performed in cases of death after non-lethal traumatic injuries to reveal any mitigating factors for perpetrators. Successful triage in the emergency room determines the severity of trauma, which directs the treatment carried out and the monitoring pathways used. Various types of scoring Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Arslan et al. Use of trauma scoring systems to determine the physician’s responsibility in cases of traumatic death with medical malpractice claim

systems are utilized for this purpose. Calculation of a trauma score provides identification of the severity of trauma, prediction of the probability of survival, and evaluation of applied treatment protocols. In the calculation process, all injuries are identified, classified, and scored.[1–4] Frequently referenced scoring systems include the Abbreviated Injury Scale (AIS), the Injury Severity Score (ISS), and New Injury Severity Score (NISS).[1,4]

the findings obtained at the last evaluation of the patient, or during autopsy. ISS and NISS of 15 or less was accepted as minor trauma (non-lethal injury if accurate treatment applied) and classed as Group 1, ISS and NISS of 16 or more was considered major trauma (lethal injury even if there is no malpractice) and categorized as Group 2, and ISS and NISS of 75 was accepted as lethal injury even if accurate treatment applied and made up Group 3 for this study.

This study provides a new approach to evaluating medical malpractice claim cases, not only for forensic medicine specialists, but also for academics from all specialties who may be called by the courts to be an expert witness to assist with determining any responsibility of the physician in the cause of death.

RESULTS

In a case of trauma patient death after possible medical malpractice, the injuries that initially led the patient to go to the hospital should be described as either “lethal injury even if there was no malpractice” or “non-lethal injury if accurate treatment applied.” It is obvious that this can be achieved by calculating trauma scores. In this way, the effect of faulty acts or omissions of physicians on the death of the patient can be determined.

MATERIALS AND METHODS Case Selection Cases were selected from the case archive of the General Committee of the Council of Forensic Medicine (GC of CFM) that were discussed and concluded between the years 2010 and 2013. GC is a second-opinion board for discussing and concluding the reports with objection, and also is the supreme decision authority of the CFM. Therefore, the decisions of the GC are the final decisions of the council. All medical malpractice case files were searched retrospectively and evaluated. Only cases of trauma were selected for the study, regardless of the type of trauma.

Data Collection For all cases included, the following records were retrieved: patient demographic data of age and sex, information about the incident (type of trauma), medical records of all health institutions involved including complete records of all injuries, medical specialties involved (general surgery, neurosurgery, etc.), diagnoses and treatment protocols (especially medical records of accused physicians collected separately); and results of ancillary tests and autopsy, if performed.

Calculation of Injury Scores and Case Classification The calculation of the ISS and NISS was carried out retrospectively according to the “Abbreviated Injury Scale 2005, Update 2008”[5] with the findings of accused physicians examined separately as well as exact trauma scores calculated with Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

A total of 263 medical malpractice cases were discussed and concluded in the GC between 2010 and 2013, and of these, there were 120 cases of inpatient stay that ended with the death of the patient. There were 26 reports (9.9% among overall medical malpractice cases and 21.7% among death cases) from this time period that met our selection criteria. One case was excluded due to the type of malpractice claimed: The physician was accused of “not administering tetanus vaccine after trauma.” All calculations and evaluations of this study were performed using those 25 files. Twentyone patients (84%) were men and 4 (16%) were women, with an overall male-to-female ratio of 5.3:1. The mean age of the patients was 36.7±17.0 years (range: 8–76 years). All cases involved 1 or more branches of surgery. In 11 cases (44%), injuries were related to general surgery, and next in frequency was neurosurgery, with 6 cases (24%). Other surgical specialties involved were 4 cases (16%) of cardiovascular surgery, 2 cases (8%) of orthopedics, 1 case of pediatric surgery, and 1 of thoracic surgery. Thirteen cases (52%) were admitted to the hospital due to a traffic accident, 4 cases (16%) were due to sharp force injury, 2 cases (8%) were due to occupational accident, 2 cases (8%) were due to firearm-related injury, and the remainder were various other types of injury. The mean duration of hospitalization for each case was 2.4±3.4 days (range: 0–13 days). Ten patients (40%) died on the same day of the trauma, and 6 patients (24%) died the next day. In these 25 case files, 34 physicians were accused of medical malpractice. In 9 cases, 2 physicians were accused, while in 16 cases, only 1 physician was accused. Of the physicians, 20 (58.8%) were specialists, 11 physicians (32.4%) were general practitioners, and 3 physicians (8.8%) were residents. Twenty-one (84%) interventions that led to accusation of malpractice occurred in state hospitals, 3 (12%) occurred in private hospitals, and 1 (4%) occurred at a teaching hospital. After the calculation of trauma scores, in 23 cases (92%) exact ISS score of the patient was greater than 16 (lethal trauma) (Group 2), and in 2 cases (8%) trauma score was less than 16 (minor trauma) (Group 1). Fifteen of 23 patients (65.2%) in Group 2 were evaluated as Group 1 in 20 the physicians’ medical records. Three patients were evaluated as Group 1 by the first accused physician but evaluated as Group 2 by a second accused physician. 329

330

Sex Age Subject

Event

Duration*

Male

47 Neurosurgery

Battery

Traffic accident

0 13

15 Neurosurgery

Traffic accident

Traffic accident 0

Neurosurgeon

Emergency room

Orthopedist

General surgeon

Emergency room

General surgeon

Ambulance doctor

Specialist

General practice

Specialist

General practice

Specialist

General practice

26 Cardiovascular surgery Sharp force

23 Neurosurgery

Male

Emergency room

General surgeon

Emergency room

General surgeon

Neurosurgeon

General surgeon

Emergency room

Orthopedist

Emergency room

General practice

Specialist

General practice

Specialist

Resident

Specialist

General practice

Specialist

General practice

Not performing required intervention

Missing an injury

Not paying attention

Not performing required intervention

Missing an injury

Not performing required intervention

Inadequate monitoring

Not performing required intervention

No consultations

Inadequate intervention

No consultations

intervention

Referral to other hospital without

No direct claim

Not paying attention

Not performing required intervention

Late refer to other hospital

Not performing required intervention

Late to provide treatment

Not performing required intervention

Discharge without consultations

Claim

Accused 1st physician

*Hospitalization duration before death. ǂISS and NISS values were calculated from medical records of accused first physician. ¥Resident in emergency medicine specialty.

Traffic accident

68 General surgery

Occupational accident

37 General surgery

Male

Traffic accident

Object tip-over

Female

18 Orthopedics

Male

Firearm injury

Sharp force

Traffic accident

Occupational accident

60 General surgery

Male

Traffic accident Fall from vehicle

25 General surgery

34 General surgery

Male

53 Neurosurgery

40 General surgery

Male

Female

Pediatric surgery

21 General surgery

Male

Fall from height

37 General surgery

50 Cardiovascular surgery Traffic accident

Male

Firearm injury

23 Neurosurgery

Male

34 General surgery

Male

Female

Male

Traffic accident Traffic accident 0

51 General surgery

Male

52 Cardiovascular surgery Traffic accident

76 Orthopedics

35 Neurosurgery

Female

Sharp force

Traffic accident

19 Thoracic surgery

33 General surgery

Male

33 Cardiovascular surgery Sharp force

Male

Degree

Emergency medicine Resident

specialist

Speciality

Table 1. Patient information and information about accused first physician

State

Private

State

Private

State

Private

State

Teaching

1–1

4–6

4–4

25–25

18–27

29–34

14–14

20–20

1–1

41–48

5–6

10–27

9–9

13–14

8–8

13–22

12–12

10–11

2–2

8–12

14–17

16–16

19–27

18–18

1–2

Hospital ISS–NISSǂ

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1–1 Hospitalization duration before death. ǂISS and NISS values were calculated from medical records of accused first physician. **ER: Emergency room physician (no speciality).

9–27

Not paying attention General practice ER** 1

State

Inadequate monitoring Specialist Pediatric surgeon 1

Traffic accident

8 Male

Female

General surgery

50 Male 13

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37 Male 12

Pediatric surgery

Fall from vehicle

State

4–6 Not performing required intervention Specialist Neurosurgeon 1 Traffic accident Cardiovascular surgery

State

36–48

29–34 State Late intervention Specialist General surgeon 0 Fall from height

State Not paying attention Specialist General surgeon 6 Firearm injury

General surgery

23 Male 11

Neurosurgery

19–27 State Late arrival at hospital Specialist Neurosurgeon 0 Traffic accident 15 Female 10

Neurosurgery

Not coming to hospital Specialist Orthopedist 0 34 Male 9

General surgery

Traffic accident

State

8–12

18–18 State intervention

Referral to other hospital without Specialist General surgeon 0 Sharp force Cardiovascular surgery 33 Male 2

1–1 Teaching Missing an injury Resident Neurosurgeon Battery Male 1

Neurosurgery

Claim Degree Speciality

Duration* Event Sex Age Subject #

Table 2. Patient information and information about accused second physician

Accused 2nd physician

Hospital ISS–NISSǂ

Arslan et al. Use of trauma scoring systems to determine the physician’s responsibility in cases of traumatic death with medical malpractice claim

When claims were assessed with respect to the first physician, in 15 cases (60%), the first physician was accused of “not performing the required intervention.” In 3 cases, the physician was accused of “missing an injury,” and in 3 cases, the physician was accused of “not having the required consultations.” In 4 cases, physicians were accused of 4 different claims, such as “starting the treatment late,” “late referral to higher level health center,” “referral without any evaluation or intervention,” and “no detailed claim.” For the second physician, in 3 cases out of 9 (33.3%), the physician was accused of “not performing the required intervention.” In 2 cases, the physician was accused of “not paying attention,” and in 2 cases, the physician was accused of “not coming or coming late to the hospital despite being called.” In 1 case, the physician was accused of “missing an injury,” and in 1 case the physician was accused of “referral to a higher level health center without having any consultations.” All patient and accused physician data, as well as information about the interventions that resulted in claim of malpractice are presented in Tables 1 and 2. In 12 of 25 cases (48%), the GC concluded that the events constituted malpractice. In 4 cases, the first physician’s intervention was found to be proper, but the second physician had committed malpractice. In 2 cases, it was concluded that both physicians’ interventions were acts of malpractice. In the remaining 6 cases, only 1 physician was accused. When the results of the GC reports were evaluated, the severity of the trauma was mentioned in only 5 reports. In 4 of these, in which the ISS was calculated to be greater 16, it Table 3. GC conclusions and number of physician interventions according to accuracy of calculated trauma score group GC conclusion

Accurate‡ Non-accurate† group group n (%)

n (%)

ISS value

Malpractice

6 (42.9)

8 (40)

No Malpractice

8 (57.1)

12 (60)

Total

14 (100)

20 (100)

0.868

NISS value

Malpractice

7 (43.8)

7 (38.9)

No Malpractice

9 (56.2)

11 (61.1)

Total

16 (100)

18 (100)

0.774

‡ Trauma score group evaluated as “Accurate”, if the trauma score group of the findings of the physicians was the same as the correct trauma score group. †Trauma score group evaluated as “Non-accurate”, if the trauma score group of the findings of the physicians was the same as the correct trauma score group. * Pearson chi-square. GC: General Committee; ISS: Injury Severity Score; NISS: New Injury Severity Score.

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was concluded that survival was not certain even in the case of correct treatment, and in 1 case, in which the ISS was equal to 16, the conclusion was “patient may survive with accurate treatment.” In the remaining cases, no conclusion was reached about the severity of the trauma. The conclusions reached by the GC decisions and the ISS values calculated are presented in Tables 3, 4 and 5.

DISCUSSION Injuries are an important public health concern. According to the 2014 report “Injuries and Violence: the Facts” from the World Health Organization (WHO), traffic accidents and falls are high on the lists of leading causes of traumatic deaths. In 2012, traffic accidents were ranked 9th and falls were ranked 21st on the list of leading causes of death, with ischemic heart diseases ranked at the top. According to a WHO prediction for 2030, deaths due to traffic accidents are expected to rise to 7th place, and falls to rise to the 17th rank.[6]

Calculated NISS results were quite similar in classification. In 1 case, the correct ISS calculated was 14, and the NISS was 17 (moved into Group 2), but the score was also elevated from 14 to 17 according to the first physician’s records. In another case, the correct NISS was calculated as 75, while the ISS was 45 (moved into Group 3), but the first physician’s findings resulted in NISS and ISS of 25. In the other cases, groups did not change according to ISS or NISS value.

In a trauma patient, one of the major factors affecting mortality is the severity of the trauma.[4,7] Various scoring systems are utilized to evaluate injuries with an objective approach. Some of these scoring systems are anatomical, and some are based on physiological status. The most widely used

Table 4. ISS and NISS values and malpractice decisions of the GC #

Accused 1st physician

Accused 2nd physician

Last evaluation Postmortema before death

Decision for 1st physician

Decision for 2nd physician

ISS NISS ISS NISS ISS NISS ISS NISS

1 1 2 1 1 9 11 16 26 Malpractice Malpractice 2 18 18 18 18 18 18 – –

Malpractice Malpractice

3 19 27 – – 27 27 27 27 Malpractice

–

4 16 16 – – 16 16 16 16 Malpractice

–

5 14 17 – – 14 17 14 17 No malpractice

–

6 8 12 – – 29 38 29 38 No malpractice

–

7 2 2 – – 26 27 26 27 No malpractice

–

8 10 11 – – 10 11 38 43 Malpractice

–

9 12 12 8 12 12 12 29 29 No malpractice Malpractice 10 13 22 19 27 27 27 – – No malpractice No malpractice 11 8 8 36 48 36 48 41 48 No malpractice Malpractice 12 13 14 29 34 25 34 – – No malpractice No malpractice 13 9 9 4 6 4 6 24 36 No malpractice No malpractice 14 10 27 – – 27 27 – – No malpractice

–

15 5 6 9 27 5 6 34 34 No malpractice Malpractice 16 41 48 – – 41 48 36 48 No malpractice

–

17 1 1 – – 13 13 25 25 No malpractice

–

18 20 20 – – 25 25 29 48 Malpractice

–

19 14 14 – – 14 14 14 14 No malpractice

–

No malpractice

–

No malpractice

–

22 25 25 – – 25 34 45 75 No malpractice

–

23 4 4 1 1 1 1 24 36 No malpractice Malpractice 24 4 6 – – 1 3 17 33 Malpractice

–

25 1 1 – – 20 21 – – Malpractice

–

Empty cell: No autopsy performed. ISS: Injury Severity Score; NISS: New Injury Severity Score; GC: General Committee.

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Conclusion

Reason

ISS–NISS

Conclusion

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20–21

Malpractice

Late diagnosis and treatment

1–1

–

– – – – –

– – – –

–

– Did not come to hospital Interventions were accurate Missed penetrating injury to abdomen Interventions were accurate Interventions were accurate – Required intervention was not performed – – – – – – – Required laboratory tests were not ordered –

18–18

Not certain¥

No No No Not certain¥ No No No No No No No Not certain¥ No

29–34 4–6 – 9–27 – – – – – – – 1–1 – –

No No No No

– 8–12 19–27 36–48

May be survivedǂ No Not certain¥ No

1–1

ISS–NISS

Any other comment

Missed displaced skull fracture and discharge Referral to other hospital without performing required interventions –

Reason

Suvivable injury with accurate treatment. ¥Survival is not certain after accurate treatment. ISS: Injury Severity Score; NISS: New Injury Severity Score; GC: General Committee.

1 16–26 Malpractice Discharge without consultations 1–2 Malpractice 2 18–18 Malpractice Not performing required intervention 18–18 Malpractice 3 27–27 Malpractice Emergency operation was needed 19–27 – but not performed 4 16–16 Malpractice Late diagnosis and treatment 16–16 – 5 14–17 No-malpractice Interventions were accurate 14–17 – 29–38 No-malpractice Interventions were accurate 8–12 – 6 7 26–27 No-malpractice Outcomes were evaluated as 2–2 – complication, complication management was accurate 8 38–43 Malpractice Missing a vessel injury 10–11 – 9 29–29 No malpractice Interventions were accurate 12–12 Malpractice 10 27–27 No malpractice Interventions were accurate 13–22 No-malpractice 11 41–48 No malpractice Required consultations were made 8–8 Malpractice 12 25–34 No malpractice Interventions were accurate 13–14 No-malpractice 24–36 No malpractice Required consultations were made 9–9 No-malpractice 13 14 27–27 No malpractice Interventions were accurate 10–27 – 15 34–34 No malpractice Interventions were accurate 5–6 Malpractice 16 41–48 No malpractice Interventions were accurate 41–48 – 17 25–35 No malpractice Interventions were accurate 1–1 – 29–48 Malpractice Missed jejenum injury 20–20 – 18 19 14–14 No malpractice Interventions were accurate 14–14 – 20 45–50 No malpractice Interventions were accurate 29–34 – 22–27 No malpractice Interventions were accurate 18–27 – 21 22 45–75 No malpractice Interventions were accurate 25–25 – 24–36 No malpractice Interventions were accurate 4–4 Malpractice 23 24 17–33 Malpractice Required consultation was not 4–6 – made (vessel injury)

# Correct Accused 1st physician Accused 2nd physician ISS-NISS

Table 5. ISS-NISS values and reasons for GC conclusion

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scoring systems are the AIS, the ISS, the NISS, the Glasgow Coma Scale (GCS), the Trauma and Injury and Severity Score (TRISS), the Revised Trauma Score (RTS), and A Severity Characterization of Trauma (ASCOT).[5,8–12] Trauma scoring systems are also used during autopsy to evaluate the effect of the trauma on cause of death. There are numerous studies comparing postmortem and antemortem trauma scores at autopsy.[2,3,13–18] In the emergency room, some injuries may be overlooked during interventions, and this may be the source of a malpractice claim. Among all medical specialties, specialties that deal with trauma carry an increased malpractice risk.[19] At the moment of admission to a health center, one of the most important steps is to determine the severity of the trauma and perform the appropriate triage on trauma patients. When evaluating a medical malpractice case, the following criteria should be considered: 1) approaches taken by the physicians; 2) whether or not the physicians provided the standard required care and attention; 3) whether informed consent was obtained; 4) whether the physician’s order required ancillary tests and whether it required consultations; 5) whether the correct diagnosis was made and whether the physician(s) ordered the correct treatment and surgical protocol; 6) whether the follow-up and monitoring were accurate; 7) whether the outcome was an expected complication, or an adverse effect; and 8) if the outcome was a complication, whether it was diagnosed in the early period and whether the complication management was protocol-correct.[19–22] Weiland et al.[21] added some other factors affecting malpractice risk: hospital designation, physician training, and management of injured patients. Determining the severity of the trauma may have a key role in concluding the malpractice claims of trauma patients concerning two points: 1) Could the physician have arrived at the correct diagnosis without missing any injury? and 2) Could the outcome have changed if there was no malpractice (if the correct treatment/surgery were administered)? In the present study, according to the trauma scores calculated from the accused physicians’ medical records, 60% of the ISS values (n=15; correct group was Group 2 while the first physician evaluated patient as Group 1), and 60% of the NISS (n=15; in 1 case, correct group was Group 3, and in 14 cases, accurate group was Group 2, but the first physician evaluated it as 1 level less) were evaluated by the physician as 1 group below the true score. For the second physician, 55.6% of the ISS (n=5) and 44.4% of the NISS (n=4) were evaluated as 1 group below the correct score (Group 2 to 1). Of course, injuries missed on the first evaluation don’t always mean that the interventions that followed were not accurate. In the end, only the interventions of 4 out of 15 physicians (26.7%) (first physician evaluated the patient as 1 group below the correct group) were concluded to be malpractice. The reasons for 334

those conclusions were 1) discharging the patient without having the required consultations, 2) missing a vessel injury, 3) not having required consultations, and 4) being late to initiate the treatment. In addition, the interventions of 4 physicians were judged to be malpractice although the first physician’s evaluation of trauma severity was accurately labeled with the correct group. The reasons for these conclusions were 1) not performing the required intervention on the scene (ambulance doctor), 2) not performing emergency surgery despite its necessity, 3) late diagnosis and treatment, and 4) missing a jejunum injury. These results indicated that determination of injury severity is important, but evaluation of a medical malpractice case should not be based solely on trauma scores. With regard to the accuracy of the trauma score groups as calculated from the medical records of accused physicians, there was no statistically significant correlation between the accuracy and the malpractice conclusion of the GC for either the ISS or the NISS (p>0.05). This demonstrates that while discussing and reaching a conclusion about the responsibility of a physician in a malpractice case, the trauma score is not enough information to evaluate the whole case. Other decisive factors should also be considered. When writing the report, trauma severity should be stated by an expert witness classified in the following 3 categories: 1) non-lethal injury, if accurate treatment is applied; 2) lethal injury although there is no malpractice; 3) lethal injury even if accurate treatment is applied. This will allow the expert witness to determine the level of responsibility of any perpetrator and the physician in the patient’s death. These conclusions may assist the judges to make decisions on guilt ratios of a perpetrator and the physician in a death with respect to both criminal and compensation law. Another point that should be discussed in medical malpractice cases is the need for autopsy. In the present study, autopsy was performed in 18 cases (72%), and of these, in 8 cases (44.4%) the correct ISS and NISS group was elevated according to the autopsy findings. In addition to the important role of autopsy findings in improving trauma management and quality assurance,[23] autopsy is mandatory in the investigation of malpractice to reveal whether or not an injury was missed. The purpose of an autopsy is not just to accuse the physician; autopsy findings may justify the actions of a defendant physician and their responsibility in the death may be reduced. Autopsy may reveal unrecognized diseases or missed injuries, or may confirm the clinical diagnosis of accused physicians. [24] In 1 case in this study, NISS value was calculated as 75 (while the physician’s score was 25) and the severity was interpreted as “lethal injury even if accurate treatment applied.” This means “the outcome would not change even if there was no malpractice.” In this case GC decided that the “required interventions were performed, required consultations were held, and there was no malpractice,” but did not mention the severity of trauma, probably because it was concluded that there was no malpractice. In the study of Enderson et al., in Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

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which missing injuries were evaluated in a university hospital medical center, musculoskeletal injuries were most frequently missed, and they concluded that closed-head injuries and alcohol or drug influence on the patient were the most frequent contributing factors to missing an injury.[25] Weiland et al.[21] also reported similar missed injury pattern, with overlooked fractures ranked first, followed by head injuries and thoracic or abdominal injuries. All missed injuries have an effect on the trauma scores of a patient on admission. A missed injury detected during autopsy may assist an expert witness to form a conclusion about the possibility of malpractice. In conclusion, a multidirectional approach should be taken in a malpractice case. Evaluating the initial diagnosis is the one step. Comparing the initial diagnosis and the final diagnosis with the ISS and NISS calculated using the initial medical records and autopsy findings may aid in establishing an accurate conclusion, especially with respect to missed injuries.

Financial Support The authors declare that they received no financial support for this study. Conflict of interest: None declared.

REFERENCES 1. Copes WS, Lawnick M, Champion HR, Sacco WJ. A comparison of Abbreviated Injury Scale 1980 and 1985 versions. J Trauma Acute Care Surg 1988;28:78–86. 2. Toka H, Karbeyaz K, Gündüz T, Balcı Y. Could postmortem ISS and NISS points sign preventable deaths? The Bulletin of Legal Medicine 2010;15:4–12. 3. İnce CH, İnce N, Taviloğlu K, Güloğlu R. A different approach to trauma scoring. Ulus Travma Acil Cerrahi Derg 2006;12:195–200. 4. Orhon R, Eren ŞH, Karadayı Ş, Korkmaz İ, Coşkun A, Eren M, et al. Comparison of trauma scores for predicting mortality and morbidity on trauma patients. Ulus Travma Acil Cerrahi Derg 2014;20:258–64. 6. Injuries and Violence. The Facts 2014. Geneva, Switzerland: World Health Organization; 2014. Available from: http://apps.who.int/iris/ bitstream/10665/149798/1/9789241508018_eng.pdf?ua=1&ua=1. 7. Özgüç H, Kaya E, Korun N. Factors affecting outcome in the resuscitation of trauma. Ulus Travma Acil Cerrahi Derg 1995;1:51–8. 8. Guidelines for Trauma Quality Improvement Programmes. Geneva, Switzerland: World Health Organization; 2009. Available from: http://apps. who.int/iris/bitstream/10665/44061/1/9789241597746_eng.pdf.

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9. Copes WS, Champion HR, Sacco WJ, Lawnick MM, Gann DS, Gennarelli T, et al. Progress in characterizing anatomic injury. J Trauma Acute Care Surg 1990;30:1200–7. 10. Günay Y. Trauma scoring and forensic medicine. The Bulletin of Legal Medicine 1999;4:65–73. 11. Baker SP, o’Neill B, Haddon Jr W, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma Acute Care Surg 1974;14:187–96. 12. Eid HO, Abu-Zidan FM. New Injury Severity Score is a better predictor of mortality for blunt trauma patients than the Injury Severity Score. World J Surg 2014;39:165–71. 13. Elçi Ç. Comparison of antemortem and postmortem trauma scores [Unpublished Thesis]. İstanbul, Turkey: The Council of Forensic Medicine, Ministry of Justice 2013. 14. Subedi N, Yadav B, Jha S. Application of Abbreviated Injury Scale and Injury Severity Score in fatal cases with abdominopelvic injuries. Am J Forensic Med Pathol 2014;35:275–7. 15. Adams VI, Carrubba C. The Abbreviated Injury Scale: application to autopsy data. Am J Forensic Med Pathol 1998;19:246–51. 16. Riddick L, Long WB, Copes WS, Dove DM, Sacco WJ. Automated coding of injuries from autopsy reports. Am J Forensic Med Pathol 1998;19:269–74. 17. Eryılmaz M, Durusu M, Cantürk G, Menteş MÖ, Özer MT. Role of anatomic and physiologic trauma scoring systems in forensic cases. Ulus Travma Acil Cerrahi Derg 2009;15:285–92. 18. Sharma BR. The injury scale--a valuable tool for forensic documentation of trauma. J Clin Forensic Med 2005;12:21–8. 19. McGwin GJ, Wilson SL, Bailes J, Pritchett P, Rue LWI. Malpractice Risk: Trauma Care Versus Other Surgical and Medical Specialties. J Trauma Acute Care Surg 2008;64:607–13. 20. Yazıcı YA, Şen H, Aliustaoğlu S, Sezer Y, İnce CH. Evaluation of the medical malpractice cases concluded in the General Assembly of Council of Forensic Medicine. Ulus Travma Acil Cerrahi Derg 2015;21:204–8. 21. Weiland DE, Malone JM, Krebs R, Ward J. Trauma malpractice claims related to trauma level designation. Am J Surg 1989;158:553–6. 22. Brennan TA, Sox CM, Burstin HR. Relation between Negligent Adverse Events and the Outcomes of Medical-Malpractice Litigation. N Engl J Med 1996;335:1963–7. 23. Rautji R, Bhardwaj D, Dogra T. The Abbreviated Injury Scale and its correlation with preventable traumatic accidental deaths: a study from South Delhi. Med Sci Law 2006;46:157–65. 24. Bove KE, Iery C. The role of the autopsy in medical malpractice cases, I: A review of 99 appeals court decisions. Arch Pathol Lab Med 2002;126:1023–31. 25. Enderson BL, Reath DB, Meadors J, Dallas W, Deboo JM, Maull KI. The tertiary trauma survey: A prospective study of missed injury. J Trauma Acute Care Surg 1990;30:666–70.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Tıbbi uygulama hatası iddiası olan travmatik ölümlerde hekim sorumluluğunun belirlenmesinde travma skoru sistemlerinin kullanılması Dr. Murat Nihat Arslan,1 Dr. Çisem Kertmen,2 Dr. Deniz Oğuzhan Melez,1 Dr. Durmuş Evcüman,3 Dr. Yalçın Büyük4 Adli Tıp Kurumu, Morg İhtisas Dairesi, İstanbul Adli Tıp Kurumu, Düzce Adli Tıp Şube Müdürlüğü, Düzce Adli Tıp Kurumu, Çanakkale Adli Tıp Şube Müdürlüğü, Çanakkale 4 Adli Tıp Kurumu, İstanbul 1 2 3

AMAÇ: Travmatik ölümler Dünya Sağlık Örgütü’nün başlıca ölüm sebepleri listesinde en üst sıralarda yer almaktadır ve bu ölümlerde mortaliteyi en fazla etkileyen faktörlerden birisi travmanın şiddetidir. Travma hastalarında tıbbi girişimler sırasında kimi yaralanmalar atlanabilmekte ve bu durum tıbbi uygulama hatası iddialarının doğmasına neden olabilmektedir. Bu çalışmanın amacı, travma skorlama sistemlerinin sağlayacağı yararı ortaya çıkarak tıbbi uygulama hatası iddiası olan olguların değerlendirilmesine yeni bir bakış açısı getirmektir. GEREÇ VE YÖNTEM: Olgulara Adli Tıp Kurumu Genel Kurulu’nda 2010–2013 yılları arasında görüşülerek karara bağlanmış dosyalar taranarak ulaşıldı. Tıbbi uygulama hatası olan hekimin tıbbi kayıtları, otopsi ya da son klinik değerlendirme bulguları göz önüne alınarak her birisi için ayrı ayrı yaralanma ağırlık soruları hesaplanarak karşılaştırıldı. BULGULAR: 2010–2013 yılları arasında 263 tıbbi uygulama hatası iddiası dosyası tartışılarak karara bağlanmıştır. Bunlardan 25’i hastanın ölümüyle sonuçlanmış olgulardır. Bu 25 olguda 34 hekim hakkında tıbbi uygulama hatası ile iddiası ortaya atışmıştır. Kurul 12 olguda 14 hekimin tıbbi uygulama hatası olduğu yönünde karar vermiştir. Hakkında iddia olan hekimin tuttuğu tıbbi kayıtlarda saptayabilmiş olduğu travma bulguları ile otopsi ya da son klinik değerlendirmede saptanan tüm bulgulara ait Yaralanma Ağırlık Skoru ve Yeni-Yaralanma Ağırlık Skoru hesaplanarak atlanmış ya da gözden kaçırılmış yaralanmaların ölüm üzerindeki etkisi ortaya konabilecektir. TARTIŞMA: Tıbbi uygulama hatası iddiası bulunan olgularda travma skorlarının hesaplanması tüm dallardan tıbbi bilirkişilikle görevlendirilmiş uzmanlara ve ayrıca hakimlere, atlanmış ya da gözden kaçırılmış yaralanmaların etkilerinin ortaya çıkarılmasında ve hekimin sorumluluğunun yorumlanmasında ve olgunun uygulama hatası olmasaydı yaşayabilme ihtimalinin belirlenmesinde yardımcı olacaktır. Tek başına karar verdirici bir ölçüt olarak değil diğer tüm bulguları destekleyici bir araç olarak kullanılabilecektir. Anahtar sözcükler: Gözden kaçırılmış yaralanmalar; tıbbi uygulama hatası; travmatik ölümler; Yaralanma Ağırlık Skoru; Yeni-Yaralanma Ağırlık Skoru. Ulus Travma Acil Cerrahi Derg 2017;23(4):328–336

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doi: 10.5505/tjtes.2016.50540

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ORIGIN A L A R T IC L E

Total hip arthroplasty for acetabular fractures: “Early Application” Necmettin Salar, M.D.,1 Muhammet Sadık Bilgen, M.D.,2 Ömer Faruk Bilgen, M.D.,3 Cenk Ermutlu, M.D.,4 Gökay Eken, M.D.,2 Kemal Durak, M.D.2 1

Department of Orthopedics and Traumatology, Private Diyarlife Hospital, Diyarbakır-Turkey

Department of Orthopedics and Traumatology, Uludağ University Faculty of Medicine, Bursa-Turkey

Department of Orthopedics and Traumatology, Private Medicabil Hospital, Bursa-Turkey

Department of Orthopedics and Traumatology, İstanbul Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The aim of this study was to evaluate the functional and clinical results of early total hip arthroplasty performed to treat acetabulum fracture. METHODS: Evaluation of 17 patients who were diagnosed with acetabulum fracture and treated with early total hip arthroplasty between January 2008 and October 2013 was performed. In all, 14 patients were male, and 3 were female, with mean age of 52 years (range: 29–80 years). Time elapsed between trauma and operation was mean of 13 days (range: 2–21 days). Observation period was average of 48.2 months (range: 24–70 months). Mean Harris Hip Score was 89.6 (range: 70–100). RESULTS: In 13 patients, score was good or excellent. Total of 7 of 10 patients had returned to their pre-trauma jobs. Mean length of time for return to work was determined to be 7.2 months (range: 1.5–24 months). Of the total, 9 (52.9%) patients were diagnosed with heterotopic ossification according to Brooker Classification. CONCLUSION: After acetabulum fracture, early total hip arthroplasty with the correct indications and appropriate patient can result in functional, pain-free hip joint with the advantages of early mobilization, early return to work, and decrease in reoperation risk. Heterotopic ossification prophylaxis should be considered in the presence of 1 or more risk factors, such as a head injury, high-energy trauma, or associated musculoskeletal injuries. Keywords: Acetabulum fracture; heterotopic ossification; total hip arthroplasty.

INTRODUCTION Acetabulum fracture is a rarely seen but serious orthopedic injury that can have early or late complications. Rate of incidence of osteoarthritis after acetabulum fracture varies between 12% and 67%.[1–6] The primary objective in patients diagnosed with displaced acetabular fracture is to prevent post-traumatic osteoarthritis and long-term functional limitation. Articular impaction of the medial wall,[7] marginal imAddress for correspondence: Muhammet Sadık Bilgen, M.D. Uludağ Üniversitesi Tıp Fakültesi Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Nilüfer, Bursa, Turkey Tel: +90 224 - 295 00 00 E-mail: msbilgen@superonline.com Submitted: 10.02.2016 Accepted: 06.12.2016

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paction of the posterior wall,[8,9] hip dislocation related to the posterior wall,[9,10] and femoral head injuries have been noted as poor results after internal fixation.[2,11] These complications increase the risk of neurovascular traumatization, loss of height, and aseptic and septic loosening.[12–14] When internal fixation is done simultaneously with early total hip arthroplasty, treatment provides fracture stabilization, pain reduction, and early mobilization. It also reduces complications related to soft tissue to a minimum via wider surgical opening and avoiding reoperation through same tissue.[15–18] The objective of this study was to retrospectively observe and assess the clinical and radiological results of total hip arthroplasty performed for acetabulum fracture.

MATERIALS AND METHODS A total of 17 of 20 patients diagnosed with acetabulum fracture and treated with total hip arthroplasty between 2008 337

Salar et al. Total hip arthroplasty for acetabular fractures: “Early Application”

and 2013 were included in the study. Three patients were excluded due to change in contact information or incomplete polyclinic check-ups. The indications for total hip arthroplasty included an impaction fracture of the femoral head with acetabular fracture, osteoporosis with impaction or comminution of the roof of the acetabulum, pre-existing osteoarthritis, or avascular necrosis. In all, 14 of the patients were male, and 3 were female; mean age was 52 years (range: 29–80 years). Mean observation period was 48.2 months (range: 24–70 months). Time elapsed between patient trauma and operation was mean of 13 days (range: 2–21 days). Examination of type of trauma revealed 2 cases of non-vehicle traffic accident (NVTA), 12 cases of vehicle traffic accident (VTA), 2 cases of a fall from a height (FDFH), and 1 same level fall (SLF). Most frequent cause of injury in our research was VTA (70%) (Table 1). All patients were operated on at the same center and by the same surgeon using the same technique and the same total hip prosthesis. The patient was placed in the lateral decubitus position, and standard lateral approach to the hip was used. A stable reduction of the anterior and posterior columns of the acetabulum was achieved with screws, plates, or cables. Fracture stabilization and acetabular bone structure were established, and for good fixation of the acetabular component, reconstruction plate and screw was used in 5 patients, cortical and cannulated screw in 8 patients, and cannulated screw and medical cables in 1 patient. Uncemented acetabular component was used in all fractures. Excised femoral head provided bone graft to introduce into residual fracture gaps or defects. Once the hemipelvis was stable, conventional acetabular reaming was performed and nonviable or damaged muscle was carefully debrided. Standard acetabular and femoral component placement and wound closure were then performed. Radiological follow-up was performed to examine and check for acetabular component’s abduction angle, medialization, loosening, wear on polyethylene insert, vertical displacement, or osteolysis, according to DeLee and Charnley.[19] Patients diagnosed with heterotopic ossification were classified using the Brooker Classification. Loosening of femoral component, osteolysis with varus or valgus shift, and collapse, as described by Gruen et al.,[20] were observed.

Clinically, patients were evaluated using the Harris Hip Score (HHS) system, which assessed items such as patient satisfaction with the hip, use of any assistive device to walk, time until return to work, and limp. Low molecular-weight heparin was administered to patients on date of admission and continuing for postoperative 35 days. For prophylactic purposes, 1 g first-generation cephalosporin, cefazolin sodium, was administered preoperatively. Postoperatively, all patients’ standing stance was restored, and they were mobilized with crutches, with exception of patients with additional fracture.

RESULTS Fracture classification was made according to Judet and Letournel.[2] Five patients had simple fracture, 12 had complex fracture. Examination of femoral head and acetabulum during operation revealed fracture of the femoral head in 3 patients, severe osteoarthritic changes in 1 patient, erosion that involved more than 3% of the femoral head in 4 patients, and erosion of cartilage in the posterior and superior areas of the acetabulum in 5 patients (Figs. 1–3). A total of 10 (58.8%) of the patients scored above 90 (excellent), 3 (17.6%) patients scored between 80 and 89 (good), 4 (23.5%) patients scored between 70 and 79 (moderate) using the HHS tool. Mean score for all patients was 89.64 (range: 70–100); outcome for 13 (76%) patients was excellent or good. When a comparison of the patients’ scores was performed according to age, it was determined that patients over the age 65 had lower HHS than other groups (Table 2). Eight (47%) patients limped when walking; in 1 case it was of moderate degree, while it was mild in the remaining patients. Four of the patients with a limp had peroneal nerve palsy, 1 had unhealed open calcaneus fracture, 2 had grade 4 heterotopic ossification, and 1 had previous limp due to cerebrovascular event. In the postoperative observation period, 4 (23.5%) patients were still using assistive devices to walk. Mean observa-

Table 1. Patients’ injury reasons and ratio of age of these injuries Fracture reason

338

Number

Percentage (%)

Average of age

Vehicle traffic accident

70.6

Non-vehicle traffic accident

11.8

Falling down from height

11.8

Same level fall

5.9

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Salar et al. Total hip arthroplasty for acetabular fractures: “Early Application”

(a)

(b)

Figure 1. (a) Pelvis radiograph of right sacrum fracture and left acetabulum fracture after vehicle traffic accident in a 54-year-old male patient. (b) Computed tomography display of the left acetabulum fracture.

(a)

(b)

Figure 2. (a) Acetabulum fracture in a 54-year-old male patient after surgical opening. (b) Damage to the weightbearing area of the femoral head.

tion period for these patients was 46 months (range: 24–58 months), and mean HHS was 79.5. Only 1 patient, who was 80 years old and was operated on for posterior wall fracture caused by NVTA, used crutches and only mobilized inside the home. Two patients used a walking stick on long walks, and 1 patient used walker.

3 (17.6%) patients, it was grade 2; in 1 patient (5.9%), grade 3; and in 2 patients (11.8%), grade 4 heterotopic ossification was detected (Table 3) (Fig. 4).

Ten patients (58.8%) were working preoperatively. Mean age of that group was 43.7 years (range: 29–55 years). In all, 7 (70%) returned to work in mean of 7.2 months (range: 1.5–24 months). Mean length of time before return to work with the single patient who began to work after 24 months excluded was 4.4 months (range: 1.5–8 months). Two (11.8%) patients reported continuing hip pain; however, the remaining patients had no complaints and were satisfied with the surgery. Patient radiographs from the last follow-up were classified according to the Brooker classification for heterotopic ossification. In 8 patients (47.1%), there was determination of grade 0. In 3 patients (17.6%), the finding was grade 1; in another Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Figure 3. (a) Radiography of 54-year-old male patient’s right sacrum fracture and left acetabulum fracture 7 months after surgical operation.

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Table 2. Harris hip scores with ages Age

Number

Harris hip score

Percentage (%)

20–29 1

5.9

30–39 3

92.6

17.6

40–49 3

17.6

50v59 7

93.2

41.1

60–69 –

–

70–80 3

77.3

17.6

Table 3. Patients’ heterotopic ossification numbers and ratio according to Brooker Classification Brooker Classification

Patient number

Percentage (%)

Grade 0

47.1

Grade 1

17.6

Grade 2

17.6

Grade 3

5.9

Grade 4

11.8

Acetabular component angle measurements were made by analyzing anteroposterior pelvis and anteroposterior hip radiographs. Mean acetabular component angle was determined to be 44.4° (range: 34°–55°). Bone union was seen on all radiographs of acetabulum fractures of all patients. One (5.9%) patient had revision surgery due to infection and medialization of the acetabular component. No acetabular component loosening, medial displacement, osteolysis according to DeLee and Charnley[19] or polyethylene corrosion were seen in any patient. Femoral component had varus tilt in 2 (11.8%) patients. Osteolysis, collapse on femur, or valgus were not seen in any zone, as defined by Gruen.[20]

(a)

Two patients were reoperated on due to complications: 1 (5.9%) patient was diagnosed with infection, and the other experienced dislocation. Deep surgical site infection was treated with 2-stage revision. Acetabular revision was performed in the patient with repeated dislocation at fourth month.

DISCUSSION Open reduction and internal fixation are generally accepted in the literature as the ideal treatment modalities for comminuted acetabulum fracture.[2,11] However, especially in comminuted acetabulum fractures, internal fixation may result in poor prognosis as result of acetabular and femoral surface impaction and erosion, even with good reduction.[21] A meta-analysis conducted by Giannoudis[22] reported 20% rate of post-traumatic arthritis as the most frequent longterm complication following acetabulum fracture, and some other authors have reported up to 60% post-traumatic arthritis. Osteonecrosis of femoral head has been reported at 5.6% to 53%.[23] U.G. De Bellis reported indications for early total hip arthroplasty on acetabulum fracture of complex fracture according to Letournel and Judet,[19] osteoarthritis in hips, femur head fracture, pathological fracture, bad bone quality, or fractures that cannot be reconstructed.[3,12,18,24] Mears added these criteria to the indications: severe impaction, wide femur head abrasion, acetabular impaction more than 30% of its surface, multipartite acetabular fracture, and more.[8] Relative indications are reported as: delayed case, medical comorbidities, obesity, and senility.[25] In the present study, 5 patients had a simple fracture and 12 patients had a complex fracture. One of these simple fracture cases had severe osteoarthritis, and 2 had osteoarthritic changes; however, these patients were over the age 70. Tidemark’s study stated 30% of patients used an assistive device for walking after undergoing total hip arthroplasty for

(b)

Figure 4. (a, b) A 47-year-old female patient diagnosed with grade 4 heterotopic ossification.

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Salar et al. Total hip arthroplasty for acetabular fractures: “Early Application”

acetabular fracture.[18] Another study performed by Mears reported 23% of patients used assistive devices for long walks, and 9% of them could even walk without device but with human support.[8] Hersovici’s study with 22 patients indicated that 5 patients used a crutch and 5 patients used a walker.[26] In our research, 4 (23.5%) of patients continued to use assistive devices for walking. The mean observation period was 42 months (range: 24–48 months), and mean HHS was 79.5. At last evaluation, 1 patient used walker, 1 other used walker and 2 used a walking stick for long walks. In Mears’ study with 57 patients, 18 (32%) patients returned to work.[8] Our study included 10 (58.8%) patients who were working preoperatively with mean age of 43.7 (range: 29–55 years). In all, 7 (70%) of them returned to work, and mean return-to-work time was 7.2 months (range: 1.5–24). When the patient who had 24-month return-to-work time was excluded, mean for the remainder of the group was 4.4 months (range: 1.5–8 months). In the present study, 11 (64.7%) patients had additional fractures: 1 humerus fracture, 4 tibia fractures, 5 femur fractures, 2 patella fractures, 1 sacrum fracture, 2 wrist fractures, 2 metacarpus fractures, and 1 calcaneus fracture. We believe these fractures delayed patients’ recovery, early walking, and early return to work. Early total hip arthroplasty patients’ implants vary in terms of acetabulum reduction and acetabular cup fixation. In our study, a reconstruction plaque and screw was used in 5 patients, cortical and cannulated screw in 8 patients, and cannulated screw and medical cables in 1 patient. In 1 patient, only uncemented acetabular component was used. When we look at complications and the ratio seen in the literature, Sermon et al. reported that of 64 patients, 18 (28%) were diagnosed with heterotopic ossification and 4 (89%) patients underwent revision.[24] Mears’ study with 57 patients indicated that 3 (5%) patients were diagnosed with deep venous thrombosis, 6 (10%) with heterotopic ossification, 2 (4%) with dislocation, and 3 (5%) underwent revision. [8] Hersovici’s research on 22 patients reported 1 (4%) transient ischemic attack, 4 (18%) cases of heterotopic ossification, 1 (4%) wound site infection, 3 (14%) dislocations, 2 (9%) instances of loosening, and 5 (23%) revisions.[26] Heterotopic ossification is a frequent complication of acetabular fracture surgery. High-energy trauma with significant inflammation, polytrauma, head injury, extensive surgery with muscle dissection and hematoma formation, blood loss, and prolonged operating time may explain it. According to Letournel and Judet,[2] the more extensive the stripping of the gluteal muscles, the greater the risk for heterotopic ossification. A meta-analysis by Giannoudis et al.[22] published in 2005 reviewed 2394 acetabular fractures and found an overall incidence of heterotopic ossification of 25.6%. The specific Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

cause of heterotopic ossification remains unclear, although many risk factors, such as the surgical approach, have been implicated. Some level of prevention seems possible with anti-inflammatory prophylaxis, especially indomethacin and/or radiotherapy,[27] but other studies have reported no benefit. Furthermore, the superiority of a single form of prophylaxis has not been proven. In our study, 9 (52.9%) of 17 patients were diagnosed with heterotopic ossification. In 3 patients, it was determined to be grade 1 (17.6%); in 3 patients, grade 2 (17.6%); in 1 patient, grade 3 (5.9%), and in 2 (11.8%) patients it was classified as grade 4 heterotopic ossification. Eight (47.1%) patients were clear for heterotopic ossification. Our patients did not receive any heterotopic ossification prophylaxis, and we think that indomethacin or radiotherapy application can diminish the heterotopic ossification rate. Two (11.8%) patients underwent revision operation: 1 (5.9%) of the patients was diagnosed with infection and the other patient (5.9%) had dislocation. We did not observe any case of loosening, deep venous thrombosis, pulmonary embolism, or periprostatic fracture in our research. When comparing our study to others, we believe that the greater rate of heterotopic ossification seen in our study was due to non-use of any prophylactic treatment. Acetabulum fracture is a serious and rarely seen orthopedic injury that can have early or late complications. Treatment of acetabulum fracture is debated in the medical literature. We think that with the correct indications and the correct selection of patient, simultaneous open reduction-internal fixation with acute total hip arthroplasty can provide excellent fracture stabilization, successful pain reduction, early mobilization, and a wider surgical approach, which by avoiding reoperation through same tissue, reduces complications related to soft tissue injury. Our study is limited by small number of patients, and lacks a longer average observation period and comparison group. Additional research on acetabulum fracture with these qualities is needed.

Conclusion Early period total hip arthroplasty for acetabulum fracture is effective based on functional and radiological results, as well as patient satisfaction, when performed with the correct indications and correct surgical technique. Conflict of interest: None declared.

REFERENCES 1. Letournel, E. Acetabulum fractures: Classification and management. Clin Orthop 1980;151:81. 2. Letournel E, Judet R. Radiology of the normal acetabulum. In: Letournel E, Judet R, editors. Fractures of the acetabulum. 2nd ed. Berlin: SpringerVerlag; 1993. 3. De Bellis UG, Legnani C, Calori GM. Acute total hip replacement for acetabular fractures: A systematic review of the literature Injury. Int J Care Injured 2013.

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Salar et al. Total hip arthroplasty for acetabular fractures: “Early Application” 4. Carnesale PG, Stewart MJ, Barnes SN. Acetabular disruption and central fracture-dislocation of the hip. A long-term study. J Bone Joint Surg Am 1975;57:1054–9. 5. Pennal GF, Davidson J, Garside H. Results of treatment of acetabular fractures. Clin Orthop Relat Res 1980;151–15. 6. Ragnarsson B, Mjöberg B. Arthrosis after surgically treated acetabular fractures. A retrospective study of 60 cases. Acta Orthop Scand 1992;63:511. 7. Anglen JO, Burd TA, Hendricks KJ, Harrison P. The “Gull Sign”: a harbinger of failure for internal fixation of geriatric acetabular fractures. J Orthop Trauma 2003;17:625–34. 8. Mears DC, Velyvis JH. Acute total hip arthroplasty for selected displaced acetabular fractures: two to twelve-year results. J Bone Joint Surg Am 2002;84:1–9. 9. Kreder HJ, Rozen N, Borkhoff CM, Laflamme YG, McKee MD, Schemitsch EH, et al. Determinants of functional outcome after simple and complex acetabular fractures involving the posterior wall. J Bone Joint Surg Br 2006;88:776–82. 10. Bhandari M, Matta J, Ferguson T, Matthys G. Predictors of clinical and radiological outcome in patients with fractures of the acetabulum and concomitant posterior dislocation of the hip. J Bone Joint Surg Br 2006;88:1618–24.

16. Hepple S, Ward A. Early outcome of acute total hip arthroplasty following acetabular fracture. J Bone Joint Surg 2003;85:98. 17. Pagenkopf E, Grose A, Partal G, Helfet DL. Acetabular fractures in the elderly: treatment recommendations. HSS J 2006;2:161–71. 18. Tidermark J, Blomfeldt R, Ponzer S, Söderqvist A, Törnkvist H. Primary total hip arthroplasty with a Burch-Schneider antiprotrusion cage and autologous bone grafting for acetabular fractures in elderly patients. J Orthop Trauma 2003;17:193–7. 19. DeLee JG, Charnley J. Radiological demarcation of cemented sockets in total hip replacement. Clin Orthop Relat Res 1976;121:20–32. 20. Gruen TA, McNeice GM, Amstutz HC. “Modes of failure” of cemented stem-type femoral components: a radiographic analysis of loosening. Clin Orthop Relat Res 1979;141:17–27. 21. Mears DC, Velyvis JH. Acute total hip arthroplasty for selected displaced acetabular fractures: two to twelve-year results. J Bone Joint Surg Am 2002;84:1–9. 22. Giannoudis PV, Grotz MR, Papakostidis C, Dinopoulos H. Operative treatment of displaced fractures of the acetabulum. A meta-analysis. J Bone Joint Surg Br 2005;87:2–9. 23. Megan A. Swanson, MD, Michael H. Huo. Total Hip Arthroplasty for Post-Traumatic Arthritis After Previous Acetabular Fractures. Semin Arthro 2008;19:303–6.

11. Matta JM. Fractures of the acetabulum: accuracy of reduction and clinical results in patients managed operatively within three weeks after the injury. J Bone Joint Surg Am 1996;78:1632–45.

24. Sermon A, Broos P, Vanderschot P. Total hip replacement for acetabular fractures. Results in 121 patients operated between 1983 and 2003. Injury 2008;39:914–21.

12. Jimenez ML, Tile M, Schenk RS. Total hip replacement after acetabular fracture. Orthop Clin North Am 1997;28:435.

25. Mouhsine E, Garofalo R, Borens O, Blanc CH, Wettstein M, Leyvraz PF. Cable fixation and early total hip arthroplasty in the treatment of acetabular fractures in elderly patients. J Arthroplasty 2004;19:344–8.

13. Mears DC. Surgical treatment of acetabular fractures in elderly patients with osteoporotic bone. J Am Acad Orthop Surg 1999;7:128–41. 14. Mears DC, Veyvis JH. Primary total hip arthroplasty after acetabular fracture. J Bone Joint Surg 2000;82:1328–53. 15. Mears DC, Velyvis JH, Chang CP. Displaced acetabular fractures managed operatively: indicators of outcome. Clin Orthop Relat Res 2003;407:173–86.

26. Herscovici D Jr, Lindvall E, Bolhofner B, Scaduto JM. The combined hip procedure: open reduction internal fixation combined with total hip arthroplasty for the management of acetabular fractures in the elderly. J Orthop Trauma 2010;24:291–6. 27. Moed BR, Maxey JW. The effect of indomethacin on heterotopic ossification following acetabular fracture surgery. J Orthop Trauma 1993;7:33–8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Asetabulum kırıklarında total kalça protezi Dr. Necmettin Salar,1 Dr. Muhammet Sadık Bilgen,2 Dr. Ömer Faruk Bilgen,3 Dr. Cenk Ermutlu,4 Dr. Gökay Eken,2 Dr. Kemal Durak2 Özel Diyarlife Hastanesi, Ortopedi ve Travmatoloji Kliniği, Diyarbakır Uludağ Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Bursa 3 Özel Medikabil Hastanesi, Ortopedi ve Travmatoloji Kliniği, Bursa 4 İstanbul Eğitim Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul 1 2

AMAÇ: Asetabulum kırıkları sonrası erken Total Kalça Protezi (TKP) uygulamasının fonksiyonel ve klinik sonuçlarının değerlendirilmesi amaçlandı. GEREÇ VE YÖNTEM: Ocak 2008–Ekim 2013 tarihleri arasında asetabulum kırığı tanısıyla erken total kalça protezi uygulanan 17 hastanın klinik ve radyolojik sonuçları değerlendirildi. On dördü erkek, üçü kadın olmak üzere, ortalama yaşları 52 (29–80) idi. Hastaların ortalama takip süresi 48.2 aydır (24 ay–70 ay). Hastaların travmaları ile operasyonları arasındaki ortalama süre 13 gündür (2 gün–21 gün). BULGULAR: Hastaların fonksiyonel sonuçları Harris kalça skoru ile değerlendirildi. Ortalama Harris kalça skoru 89.6 (70–100) olarak bulundu. On üç (%76) hastada ise mükemmel ve iyi olarak bulundu. On hastanın yedisi travmadan önce çalıştıkları işe geri döndü. Ortalama işe dönüş süresi ise 7.2 ay (1.5 ay–24 ay) idi. Komplikasyon olarak kısalık, enfeksiyon, dislokasyon ve heterotopik ossifikasyon görüldü. Enfeksiyon ve dislokasyon nedeniyle iki hastaya revizyon uygulandı. Dokuz (%52.9) hastada Brooker sınıflamasına göre heterotopik ossifikasyon tespit edildi. TARTIŞMA: Asetabulum kırıklarından sonra doğru endikasyon ve doğru hasta seçimi ile yapılan erken TKP ile ağrısız ve fonksiyonel bir kalça eklemi elde edilirken, erken mobilizasyon, erken işe dönüş ve tekrar operasyon riskinde azalma avantajları olduğu anlaşılmıştır ve kafa travması, yüksek enerjili travma ya da ek kas iskelet sistemi yaralanmasından biri veya daha fazlası olan hastalarda heterotopik ossifikasyon profilaksisi akılda tutulmalıdır. Anahtar sözcükler: Asetabulum kırığı; heterotopik ossifikasyon; total kalça artroplastisi. Ulus Travma Acil Cerrahi Derg 2017;23(4):337–342

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doi: 10.5505/tjtes.2016.55675

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ORIGIN A L A R T IC L E

Is intact fibula a disadvantage in treatment of tibial diaphysis fracture with intramedullary nailing? Yavuz Kabukçuoğlu, M.D., Sami Sökücü, M.D., Çağrı Özcan, M.D., Kubilay Beng, M.D., Osman Lapçin, M.D., Bilal Demir, M.D. Department of Orthopedics and Traumatology, Baltalimanı Bone Diseaeses Training and Reserach Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The aim of this study was to compare solitary tibial diaphysis fractures and tibial diaphysis fractures associated with fibula fracture treated with the intramedullary nailing method. METHODS: Records of 254 patients diagnosed with tibial diaphysis fracture and treated with intramedullary nailing between 2010 and 2013 were examined and 30 patients were included in the study. Group 1 comprised patients with solitary tibial diaphysis fracture, and Group 2 was made up of patients with tibial diaphysis fractures associated with fibula fracture. Patients in both groups were compared in terms of time to surgery, duration of surgical tourniquet, time to union, and varus, valgus, recurvatum, and antecurvatum deformities of the tibia at final follow-up. RESULTS: No statistically significant difference was found between the 2 groups in time to surgery, duration of surgical tourniquet, time to union, or varus, valgus, recurvatum, and antecurvatum deformities. CONCLUSION: Results indicated that intact fibula in tibial diaphysis fracture treated with intramedullary nailing was not a disadvantage; it did not affect rate of union or lead to loss of reduction, non-union, or malunion. Keywords: Fibula; intramedullar nailing; tibia diaphysis.

INTRODUCTION Tibia fracture is the most commonly encountered fracture of the long bones. Majority are accompanied by fibula fracture, at the same or different level. However, it is possible that fibula fracture may not occur with tibia fracture in lowenergy injury.[1,2] Fixation of the accompanying fibula fracture for stability is still a matter of debate in the surgical treatment of tibia fracture. While some authors advocate fixing fibula fracture during surgical treatment of tibia fracture, others suggest that this fixation does not have beneficial effect on stability.[3–5] Little information is available on fixation of concomitant or solitary fibula fracture in the surgical treatment of proximal tibial and tibial diaphysis fractures.[5] Address for correspondence: Sami Sökücü, M.D. Baltalimanı Kemik Hastalıkları Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul, Turkey Tel: +90 212 - 323 70 75 E-mail: samisorth@gmail.com Submitted: 24.01.2016 Accepted: 08.11.2016

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Although intramedullary nailing is considered the gold standard in the surgical treatment of tibial diaphysis fracture, the surgical treatment of concomitant fibula fracture in this region is controversial. While surgical approach is recommended for fibula fracture level with the tibial diaphysis, the approach is avoided if the fibula fracture occurs at a level other than the tibial diaphysis.[5–7] The aim of the present study was to compare time to surgery, duration of surgical tourniquet, and rates of non-union and healing of solitary tibial diaphysis fractures (AO 4.2.A1.1) and tibial diaphysis fractures associated with fibula fracture (AO 4.2.A1.2) treated with the intramedullary nailing method.

MATERIALS AND METHODS Data of 254 patients diagnosed with tibial diaphysis fracture and treated with intramedullary nailing between 2010 and 2013 were retrospectively evaluated. Patients who were younger than 18 years of age, had open or pathological fracture, suffered multi-trauma injuries, or who had fracture type other than AO 4.2 A1 according to the AO/OTA Classification of Fractures and Dislocations were excluded. Thirty patients (14 males, 16 females) who met the above criteria were included in the study. Mean age was 34 years (range: 18 343

KabukĂ§uoÄ&#x;lu et al. Is intact fibula a disadvantage in treatment of tibial diaphysis fracture with intramedullary nailing?

to 66 years). Group 1 comprised patients with solitary tibial diaphysis fracture (AO 4.2 A1.1), and Group 2 was made up of patients with tibial diaphysis fracture associated with fibula fracture (AO 4.2 A1.2). Anteroposterior and lateral radiographs of the knee and ankle joints of the patients were taken in the emergency department after the injury. Long-leg splints were applied to patients scheduled to be operated on within first 48 hours. Patients whose surgical treatment was planned for after first 48 hours had skeletal traction applied and their surgery was scheduled for the first day possible. All of the patients had regional anesthesia administered. Reaming was performed before nail insertion and all fractures were reduced with closed technique. Tibial intramedullary nails were inserted with transpatellar approach in all patients while in supine position and without use of traction table by experienced trauma surgeons. Another doctor assisted with traction during reduction procedure. Two static screws were introduced at the proximal and distal fragments of the nail and fixation was achieved. None of the patients

required application of plaster splint for further fixation post surgery. Knee and ankle exercises were initiated on first postoperative day. All patients were mobilized with a pair of crutches on the first day. Patients were reviewed at 2nd, 4th, 6th, 8th, and 12th week, and radiographs were taken at 6th and 12th week. Patients were allowed partial weight-bearing with crutches during this period. Clinical and radiological assessments were performed to confirm union, defined as callus formation in 3 cortices and absence of clinical pain. Patients were allowed full weight-bearing thereafter (Figs. 1, 2). Patients in both groups were compared in terms of time to surgery, duration of surgical tourniquet, time to union, and varus, valgus, recurvatum and antecurvatum deformities of the tibia at final follow-up. Statistical comparisons were made using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA) and Mann-Whitney U test. P value of <0.05 was considered statistically significant.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

Figure 1. (a-d) Preoperative anteroposterior and lateral radiographs of tibia fracture with intact fibula. (e, f) Postoperative anteroposterior and lateral radiographs. (g-i) Anteroposterior and lateral radiographs and orthoroentgenograms of the patient at last follow-up.

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(a)

(d)

(b)

(e)

(c)

(h)

(f)

(g)

Figure 2. (a-c) Preoperative anteroposterior and lateral radiographs of tibia fracture with fibula fracture. (d, e) Postoperative anteroposterior and lateral radiographs. (f-h) Anteroposterior and lateral radiographs and orthoroentgenograms of the patient at last follow-up.

RESULTS Group 1, in which the fibula was intact but tibial diaphysis was fractured, consisted of 12 patients (8 male, 4 female), and Group 2, in which both the fibula and the tibial diaphysis were fractured, comprised 18 patients (8 male, 10 female). Mean age of the patients was 29.4 years (range: 19 to 60 years) in Group 1, and 38.6 years (range: 18 to 66 years) in Group 2. Patients in Group 1 had mean follow-up period of 19.2 months (range: 12 to 36 months), whereas Group 2 patients were followed up for mean of 20 months (range: 12 to 36 months). No statistically significant differences were detected between groups in terms of age or follow-up period (p=0.751; p=0.400).

utes (range: 60 to 160 minutes) in Group 2. Again, no statistically significant difference was found between the 2 groups (p=0.991). None of the patients experienced intraoperative complication or had early or late infection symptom during follow-up period. Non-union was not observed in any patient. Mean time to union was 75 days (range: 60 to 120 days) in Group 1, and 92 days (range: 60 to 180 days) in Group 2. Dynamization was performed due to delayed union in 1 patient in Group 2. Table 1. Comparison of the groups in terms of varus, valgus, recurvatum, and antecurvatum deformities at final follow-up

Mean time to surgery was 5.1 days (range: 2 to 9 days) for Group 1, and 4.1 days (range: 1 to 15 days) for Group 2. There was no statistically significant difference between groups (p=0.226).

Antecurvatum

Duration of surgical tourniquet was noted as mean of 102 minutes (range: 60 to 150 minutes) in Group 1, and 101 min-

Recurvatum

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Group 1

Group 2

Varus

0.78° (0–2)

1.12° (0–4.2)

=0.869

Valgus

0.09° (0–1.1)

0.67° (0–3.6)

=0.512

1.09° (0–6)

0.35° (0–2.3)

=0.400

0.15° (0–1.1)

0.86° (0–6.7)

=0.981

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Union was clinically and radiologically confirmed on 30th day following dynamization. Digital orthoroentgenograms of Group 1 patients taken at final follow-up revealed mean varus angulation of 0.78° (range: 0 to 2°), valgus angulation of 0.09° (range: 0 to 1.1°), antecurvatum angulation of 1.09° (range: 0 to 6°), and recurvatum angulation of 0.15° (range: 0–1.1°). The same values were 1.12° (range: 0 to 4.2°), 0.67° (range: 0 to 3.6°), 0.35° (range: 0 to 2.3°), and 0.86° (range: 0 to 6.7°), respectively, in Group 2. No statistically significant difference was found between groups (Table 1).

DISCUSSION Treatment of tibial diaphysis fracture with intact fibula is a matter of debate. Although some studies have shown that intact fibula can lead to delayed union in conservative treatment of the tibial diaphysis fracture, others suggest that intact fibula is a good prognostic factor and will increase stability.[2,8,9] Effect of the fibula on stability in the surgical treatment of extra-articular tibia fracture is controversial. Some studies have suggested that absence of or fixation of concomitant fibula fracture in case of extra-articular tibia fracture will increase stability, while others argue that fixation does not provide an additional benefit and is an additional surgical procedure.[10–12] Most of these debates are related to extra-articular distal tibia fracture (AO 4.3); discussion of AO 4.2 diaphyseal fracture is still limited.[5] In a study of tibial diaphysis fractures treated with external fixator, Gotzen et al. reported that fixation of the fibula with plating increased stability. Similarly, in a cadaver study in which the authors fixed tibia fractures with external fixator, Morrison et al. concluded that fixation of the fibula with plating increased stability by 2.2 times in axial loading, but did not have an effect on torsional stability.[11,13] Weber et al. created tibia defects in cadavers for a biomechanical study that investigated axial and bending forces. The authors observed increased movement in the defect area following fibular osteotomy and external fixation of the tibial segmental defects; however, encountered no such increase in movement where they treated the tibial defects with intramedullary nailing.[3] In our study, all patients were treated with intramedullary nailing and no insufficiency in stability due to movement on the fracture line was observed in either group. In addition, there was no statistically significant difference between the 2 groups in rate of union. It is known that the fibula bears 3% to 16% of the load in axial loading.[14,15] It is believed by some that intact or fixed 346

fibula provides additional support to stability in fracture of diaphyseal region of the tibia. Strauss et al. stated that fibula fracture level with tibia fracture decreased stability of the tibial fixation, and that stability was improved with intact or fixed fibula.[7] In our study, none of the patients in Group 2 (with fractured fibula) suffered non-union or deformity due to insufficient stability. In their series of 38 patients, Bonnevialle et al. treated tibia fractures with intact fibula using reamed intramedullary nail and observed fracture gap increase in 5 patients. They performed dynamization on 6 patients due to delayed union and replaced nail in 2 of these 6 patients due to non-union.[16] None of the patients in Group 1 (with intact fibula) of the present study experienced either fracture gap increase, delayed union, or non-union. Retrospective design of this study, limited number of cases in both groups, occurrence of tibial fracture outside the proximal and distal metaphyseal regions, and variety of fracture levels in Group 2 patients are limitations of our study. In conclusion, fixation of the fibula in tibia fracture is still a matter of debate. Our study results indicated that intact fibula in tibial diaphysis fractures treated with intramedullary nailing will was not a disadvantage; it did not affect rate of union, or lead to loss of reduction, non-union, or malunion. Conflict of interest: None declared.

REFERENCES 1. Sanders RW, DiPasquale TG, Jordan CJ, Arrington JA, Sagi HC. Semiextended intramedullary nailing of the tibia using a suprapatellar approach: radiographic results and clinical outcomes at a minimum of 12 months follow-up. J Orthop Trauma 2014;28 Suppl 8:S29–39. 2. O’Dwyer KJ, DeVriese L, Feys H, Vercruysse L. Tibial shaft fractures with an intact fibula. Injury 1993;24:591–4. 3. Weber TG, Harrington RM, Henley MB, Tencer AF. The role of fibular fixation in combined fractures of the tibia and fibula: a biomechanical investigation. J Orthop Trauma 1997;11:206–11. 4. Egol KA, Weisz R, Hiebert R, Tejwani NC, Koval KJ, Sanders RW. Does fibular plating improve alignment after intramedullary nailing of distal metaphyseal tibia fractures? J Orthop Trauma 2006;20:94–103. 5. Berlusconi M, Busnelli L, Chiodini F, Portinaro N. To fix or not to fix? The role of fibular fixation in distal shaft fractures of the leg. Injury 2014;45:408–11. 6. Varsalona R, Liu GT. Distal tibial metaphyseal fractures: the role of fibular fixation. Strat Traum Limb Recon 2006;1:42–50. 7. Strauss EJ, Alfonso D, Kummer FJ, Egol KA, Tejwani NC. The effect of concurrent fibular fracture on the fixation of distal tibia fractures: a laboratory comparison of intramedullary nails with locked plates. J Orthop Trauma 2007;21:172–7. 8. Teitz CC, Carter DR, Frankel VH. Problems associated with tibial fractures with intact fibulae. J Bone Joint Surg Am 1980;62:770–6. 9. Leach RE. Fractures of the tibia and fibula. In: Rockwood CA, Green DP (eds). Fractures in Adults, Philadelphia: JB. Lippincott Co, Ch.

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Kabukçuoğlu et al. Is intact fibula a disadvantage in treatment of tibial diaphysis fracture with intramedullary nailing? 1984;2:17. 10. Kumar A, Charlebois SJ, Cain EL, Smith RA, Daniels AU, Crates JM. Effect of fibular plate fixation on rotational stability of simulated distal tibial fractures treated with intramedullary nailing. J Bone Joint Surg Am 2003;85-A:604–8. 11. Morrison KM, Ebraheim NA, Southworth SR, Sabin JJ, Jackson WT. Plating of the fibula. Its potential value as an adjunct to external fixation of the tibia. Clin Orthop Relat Res 1991;266:209–13. 12. Varsalona R, Liu GT. Distal tibial metaphyseal fractures: the role of fibular fixation. Strat Traum Limb Recon 2006;1:42–50.

13. Gotzen L, Haas N, Hütter J, Köller W. The importance of the fibula for stability in plate osteosynthesis of the tibia (author’s transl). Unfallheilkunde 1978;81:409–16. 14. Lambert KL. The weight-bearing function of the fibula. A strain gauge study. J Bone Joint Surg Am 1971;53:507–13. 15. Takebe K, Nakagawa A, Minami H, Kanazawa H, Hirohata K. Role of the fibula in weight-bearing. Clin Orthop Relat Res 1984;184:289–92. 16. Bonnevialle P, Bellumore Y, Foucras L, Hézard L, Mansat M. Tibial fracture with intact fibula treated by reamed nailing. Rev Chir Orthop Reparatrice Appar Mot. 2000;86:29–37.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Tibia kırığının intramedüller çivi ile tedavisinde, intakt fibula dezavantaj mıdır? Dr. Yavuz Kabukçuoğlu, Dr. Sami Sökücü, Dr. Çağrı Özcan, Dr. Kubilay Beng, Dr. Osman Lapçin, Dr. Bilal Demir Baltalimanı Kemik Hastalıkları Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul

AMAÇ: Çalışmamızın amacı, intramedüller çivi ile tedavi edilen fibula kırığının eşlik etmediği tibia diafiz kırıkları ile fibula kırığının eşlik ettiği aynı tip tibia diafiz kırıklarının cerrahi süre, kaynamama, yanlış kaynama ve iyileşme oranlarını karşılaştırmaktır. GEREÇ VE YÖNTEM: 2010–2013 yılları arasında tibia diafiz kırığı tanısı konulan ve intramedüller çivi ile tedavi edilen 254 hasta geriye dönük olarak incelendi. Çalışma kriterlerine uyan hastalar iki gruba ayrıldı. Her iki gruptaki hastalar, cerrahi öncesi geçen süre, cerrahi turnike zamanı, kaynama zamanları ve son kontrollerindeki tibia varus, valgus, rekurvatum ve antekurvatum deformiteleri açısından karşılaştırıldı. BULGULAR: Her iki grup arasında cerrahi öncesi geçen süre, cerrahi turnike zamanı, kaynama zamanları ve son kontrollerindeki tibia varus, valgus, rekurvatum ve antekurvatum deformiteleri açısından istatistiksel olarak anlamlı fark tespit edilmedi. TARTIŞMA: İntramedüller çivi ile tedavi edilen tibia diafizer kırıklarında fibulanın sağlam olması redüksiyon kaybı, kaynamama, yanlış kaynama, ve iyileşme oranları bakımından bir dezavantaj değildir. Anahtar sözcükler: Fibula; intramedüller çivi; tibia diafiz kırık. Ulus Travma Acil Cerrahi Derg 2017;23(4):343–347

doi: 10.5505/tjtes.2016.46529

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Removal of cardiothoracic war-related shrapnel using video-assisted thoracoscopic surgery Mohammed Khalifa, M.D.,1 Fikri M Abu-Zidan, M.D.,2 Navidul Khan, M.D.,3 Edward Black, M.D.1 1

Department of Surgery, Surgical Institute, Al-Ain Hospital, Al-Ain-UAE

Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain-UAE

Department of Pathology, Tawam Hospital, Al-Ain-UAE

ABSTRACT This is the first report in the literature to describe removing war-related cardiothoracic shrapnel using video-assisted thoracoscopic surgery (VATS). War blast caused penetrating thoracic and extremity injuries in 30-year-old man. He was referred to our hospital after stabilization. Magnetic resonance imaging was required to evaluate brachial plexus injury. Large, penetrating shrapnel fragment in the right posterior chest wall, retained shrapnel in apex of the right lung, and another fragment in the pericardium were removed using VATS in staged approach. Postoperative period was uneventful.VATS is useful in managing complex, war-related cardiothoracic injuries. Keywords: Blast; shrapnel; video assisted thoracoscopy; war.

INTRODUCTION Video-assisted thoracoscopic surgery (VATS) is commonly used to evaluate the diaphragm in penetrating injuries, remove retained hemothorax, evacuate empyema, and treat persistent pneumothorax in trauma patients.[1,2] It has also been used to remove bullets and other foreign bodies from the pleural cavities[1–3] and the pericardium.[4] Presently described is the first case in the literature in which VATS was used to treat war-related shrapnel injuries to the chest wall, pericardium, lung, and pleural space in a single patient.

CASE REPORT A 30-year-old man was injured in a war-related blast. Intercostal chest tube was inserted for right hemopneumothorax. The patient was transferred to our hospital 8 days after the injury for further management. On arrival, he had complete loss of right upper limb function. Address for correspondence: Fikri M Abu-Zidan, M.D. POBox 17666 Al-Ain - United Arab Emirates Tel: 00971508835390 E-mail: fabuzidan@uaeu.ac.ae Submitted: 14.02.2016 Accepted: 19.09.2016

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Computed tomography (CT) revealed laceration of upper lobe of the right lung combined with loculated right pleural space. There were multiple shrapnel fragments in the right upper chest wall and left side of the mediastinum. Lower lobe of the left lung was collapsed. Right second through fifth ribs were shattered. Largest fragment was embedded within the soft tissue of the right scapula and appeared to have traversed the chest, smashing the ribs, and lacerating the right upper lobe (Fig. 1a). Left mediastinal foreign body was not initially a concern. Electrocardiogram was normal. Management of the right-sided lung laceration and hemopneumothorax, and collapsed left lower lobe were priority. Large chest wall fragment was causing a lot of pain and was an infection risk. Large blood-stained mucous plug was removed from the left lower lobe with rigid bronchoscopy. Right-sided VATS with anterior 3-port approach using 30°, 10-mm scope (Endocameleon Hopkins telescope; Karl Storz GmbH & Co. KG, Tuttlingen, Germany) was performed. The pleural space was thoroughly cleaned. The right upper lobe was lacerated in posterior segment and bleeding continuously. This was controlled with wedge resection using Echelon endostapler (Ethicon, Inc., Somerville, NJ, USA). Extensive chest wall hematoma was observed. Fluoroscopy screening revealed large fragment in the posterior chest wall, which was removed using VATS in order to avoid another incision (Fig. 1b). A 28-F chest tube was inserted through 1 port and remaining ports were closed in layers. Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Abu-zidan et al. Removal of cardiothoracic war-related shrapnel using video-assisted thoracoscopic surgery

Postoperatively, shoulder pain of the patient resolved, and chest wounds completely healed. Drain was removed while the left lower lobe remained inflated. Histopathology of resected posterior segment demonstrated intra alveolar hemorrhage and hyperplasia of Type II pneumocytes with clear cytoplasm, typical of blast injury (Fig. 1c).

Electromyography suggested brachial plexus injury. Therefore, magnetic resonance imaging (MRI) was recommended. Accordingly, it was necessary to remove left-sided shrapnel. On repeat chest X-ray, fragment appeared to have moved. Transthoracic echocardiogram showed moving reverberation artifact posterior to the left of the aorta (Fig. 2a), indicating

(a)

(b)

(c)

Figure 1. (a) Chest computed tomography with intravenous contrast reveals foreign body in the right chest (closed arrow head), associated rib fractures, and contusion of the right lung. This shrapnel fragment was removed through the pleura. (b) Metallic foreign body (arrow) is removed with forceps using video-assisted thoracoscopy. (c) Histopathology of the resected posterior segment of the right upper lobe illustrating intra alveolar hemorrhage and hyperplasia of Type II pneumocytes with clear cytoplasm (open arrow heads) (hematoxylin-eosin, x40).

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(c)

Figure 2. (a) Transthoracic point-of-care ultrasound image taken using portable machine and convex array probe with frequency of 3-5 MHz illustrates 4-chamber apical view of the heart while the patient was in supine position. Consistent moving reverberation artifact posterior to left of the aorta (arrow heads) indicates presence of foreign body. It was difficult to define whether foreign body was in the pericardium or in the cardiac wall. (b) Computed tomography scan of the chest with intravenous contrast showed shrapnel to be in exactly the same position in supine position (arrow). (c) Foreign body moved anteriorly when the patient was put in prone position (arrow).

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presence of foreign body, which was confirmed by chest CT scan (Fig. 2b). CT scan was repeated in prone position and confirmed that foreign body was freely mobile in the pericardium (Fig. 2c).

of beaker glass following laboratory explosion. First VATS operation in our patient facilitated removing foreign body, assessing lung injury, cleaning the pleura properly, and ensuring good drain placement and lung expansion.

Left-sided VATS in supine position was performed with aid of fluoroscopy screening. Supine position was chosen to control movement of mobile fragment within operative field. Zero degree, 10-mm, 3-dimensional VATS scope was used. The foreign body was easily found and removed through 1 cm pericardial incision anterior to inferior pulmonary vein. This small pericardial incision did not require closure. Chest drain was not required. The patient completely recovered without complications.

Correct preoperative anatomical localization of left-side shrapnel and recognizing that it was mobile within the pericardium was essential for success. Positioning the patient properly reduced chance of shrapnel moving into the pericardial sinuses, which would have made extraction of the fragment more difficult. Intraoperative imaging was useful in localizing the shrapnel and minimizing pericardial incision. [2,4] Small, 1-cm incision in the pericardium reduced risk of cardiac herniation. There was no need to close this incision of the pericardium or to insert chest tube in second VATS procedure.

DISCUSSION Majority of war-related shrapnel injuries can be treated conservatively or with chest tube insertion.[5] Metallic foreign bodies inside the chest are usually not removed unless they are large, sharp, or present risk of further injury or embolization. They usually become encased in fibrous tissue and become harmless.[1,2,5] In this patient, there was a large foreign body causing pain and another that was mobile in the pericardial sac. There was risk of cardiac injury if MRI was performed. Villavicencio et al.[6] reviewed more than 500 patients and found that thoracoscopy prevented need for thoracotomy or laparotomy in 62% of trauma patients. They also reported procedure had complication rate of only 2% and missed injury rate of 0.8%. Similarly, VATS reduces postoperative pain and hospitalization and allows earlier return to work compared with thoracotomy.[1,2] Type of lung injury encountered in this case and procedure used to remove chest foreign body is very similar to those reported by Stafman et al.,[3] although they removed fragment

The patient gave written consent to report this case. Conflict of interest: None declared.

REFERENCES 1. Radjou AN, Uthrapathy M. Video-assisted thoracoscopy in trauma: Case report and review of literature. Lung India 2011;28:142–4. 2. Marsico GA, Almeida AL, Azevedo DE, Venturini GC, Azevedo AE, Marsico Pdos S. Video-assisted thoracoscopic removal of foreign bodies from the pleural cavity. J Bras Pneumol 2008;34:241–4. 3. Stafman LL, Gutwein LG, Ang DN. Use of video-assisted thoracoscopic surgery in penetrating chest trauma. J Thorac Cardiovasc Surg 2013;146:979. 4. Khalil MW, Khan T, Gower S, Loubani M. Removal of a bullet in the pericardial cavity by video-assisted thoracoscopic surgery. Interact Cardiovasc Thorac Surg 2012;15:297–8. 5. Behbehani A, Abu-Zidan F, Hasaniya N, Merei J. War injuries during the Gulf War: experience of a teaching hospital in Kuwait. Ann R Coll Surg Engl 1994;76:407–11. 6. Villavicencio RT, Aucar JA, Wall MJ. Analysis of thoracoscopy in trauma. Surg Endosc 1999;13:3–9.

OLGU SUNUMU - ÖZET

Savaş yaralanmalarından kalan kardiyotorasik şarapnellerin çıkartılması video yardımlı torakoskopik cerrahi yoluyla Dr. Mohammed Khalifa,1 Dr. Fikri M Abu-Zidan,2 Dr. Navidul Khan,3 Dr. Edward Black1 Al-Ain Hastanesi Cerrahi Enstitü, Al-Ain-Birleşik Arap Emirlikleri UAE Üniversitesi Tıp ve Sağlık Bilimleri Koleji, Cerrahi Bölümü, Al-Ain-Birleşik Arap Emirlikleri Tawam Hastanesi, Patoloji Kliniği, Al-Ain-Birleşik Arap Emirlikleri

1 2

Bu yazıda, video yardımlı torakoskopik cerrahi (VYTC) yoluyla savaş yaralanmalarında, kalan kardiyotorasik şarapnellerin çıkartılmasına dair literatürdeki ilk olgu raporlandı. Penetran torasik ve ekstremite yaralanmalarına neden olan patlama sonucu yaralanmış 30 yaşında bir erkek, stabilize olduktan sonra hastanemize sevk edildi. Brakiyal pleksus yaralanmasını değerlendirmek için bir manyetik rezonans görüntülemeye gerek vardı. Aşamalı bir yaklaşımla VYTC kullanarak sağ göğüs arka duvarında geniş penetran bir şarapnel, sağ akciğer apeksinde takılı kalmış bir şarapnel ve perikart içindeki başka bir şarapnel çıkartıldı. Ameliyat sonrası dönem olaysız geçti. Kompleks kardiyotorasik savaş yaralanmalarıyla baş etmek için VYTC yararlıdır. Anahtar sözcükler: Patlama; savaş, şarapnel; video yardımlı torakoskopi; VYTC. Ulus Travma Acil Cerrahi Derg 2017;23(4):348–350

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A rare cause of hemoperitoneum: A case report of ruptured ileocolic artery aneurysm Adem Bayraktar, M.D., Kaan Gök, M.D., Fatih Yanar, M.D., Bahar Canbay Torun, M.D. Cemalettin Ertekin, M.D. Department of General Surgery, İstanbul Universty İstanbul Faculty of Medicine, İstanbul-Turkey

ABSTRACT Visceral artery aneurysm (VAA) is very rare among vascular pathologies. Incidence reported in autopsy series and angiographic studies varies between 0.1% and 0.2%. Most cases are asymptomatic and are diagnosed as result of complications, or incidentally, when imaging is performed for another reason. Three percent of VAAs are superior mesenteric artery (SMA) terminal branch aneurysms. Intra- and/ or extraperitoneal bleeding due to ruptured aneurysm is life-threatening condition and requires emergent intervention. Therefore, surgical or endovascular interventional treatment must be performed rapidly after diagnosis. Presently described is case of ileocolic artery aneurysm in a patient admitted with abdominal pain, nausea, and vomiting. Endovascular intervention had been planned; however, during hospitalization, aneurysm ruptured and emergent surgery was performed. Review of the literature is also presented. Keywords: Acute abdomen; aneurysmal rupture; vascular aneurysm.

INTRODUCTION Visceral artery aneurysm (VAA) is very rare among vascular pathologies. VAA was first described by Beaussiers in 1770, a splenic artery aneurysm found at autopsy. In 1871, Quincke described the symptoms of hepatic artery aneurysm. Kehr performed the first successful surgical procedure to treat VAA in 1903, and in 1932, Lindboe was the first to diagnose splenic aneurysm preoperatively with abdominal X-ray. Most cases are asymptomatic and are diagnosed as result of complications, or incidentally, when imaging is performed for another reason. Reported incidence has increased in recent years due to frequent use of imaging methods.[1] In autopsy series, incidence varies between 0.1% and 0.2%.[2] Three percent of VAAs are superior mesenteric artery (SMA) terminal branch aneurysms. Aneurysm is most commonly seen in the jejunal artery, followed by the middle colic artery, and Address for correspondence: Adem Bayraktar, M.D. İstanbul Üniversitesi İstanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul, Turkey Tel: +90 212 - 631 13 66 E-mail: dradem61@gmail.com Submitted: 03.02.2016 Accepted: 07.11.2016

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the ileal artery.[3,4] Most common causes are atherosclerosis, angiodysplasia, arteritis, and infection.[3,5] Intra- and/or extraperitoneal bleeding as result of ruptured aneurysm is lifethreatening condition and requires emergent intervention. Therefore, surgical or endovascular interventional treatment must be performed rapidly after diagnosis. In this article, we report a case of ileocolic artery aneurysm in a patient who was admitted with abdominal pain, nausea, vomiting. Endovascular intervention had been planned; however, during hospitalization, the aneurysm ruptured and emergent surgery was performed. We also present a review of the literature.

CASE REPORT A 27-year-old male patient was admitted to emergency surgery department with abdominal pain. Physical examination revealed tenderness in the right lower quadrant of abdomen. Vital signs were stable. Abdominal ultrasonography (USG) demonstrated aneurysmal vascular lesion 57x52 mm in size in the right lower quadrant, which was thought to originate from mesenteric vessels, and inside the aneurysmal sac there was a hyperechoic lesion with fluid level that could indicate thrombus. Abdominal and thoracic computerized tomography (CT) and CT angiography were performed. Aneurysmal dilatation distal to ileocolic artery approximately 5 cm in diameter was found. There was no additional vascular aneurysm or vascular 351

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pathology observed in thoracic or abdominal images or cardiovascular system images (Figs. 1, 2). Hemoglobin level was 10.2 g/dL, hematocrit value was 31.3%, and other coagulation parameters were normal. The patient did not have any signs of acute abdomen. Endovascular treatment was planned. While hospitalized awaiting endovascular intervention, patient had sudden onset of abdominal distension, hypotension, and tachycardia. Emergent abdominal USG was performed, and extensive intraabdominal fluid was observed. The patient underwent emergent surgery with diagnosis of ruptured aneurysm. In exploratory laparotomy, large quantity of fresh blood in the abdomen, giant hematoma in the small bowel mesentery, and ruptured aneurysm in the terminal branches of ileocolic artery were detected (Fig. 3).

Figure 1. Axial computed tomography angiography image of aneurysmal dilatation approximately 5 cm in diameter located distal to ileocolic artery.

Figure 3. View of ileocolic arterial aneurysm rupture.

Preoperative blood pressure was 70/50 mmHg, pulse was 120/bpm, hemoglobin was 5.1 g/dL, hematocrit was 15.3%, pH was 7.05, lactate concentration was 6.3 mmol/L, and base deficit was determined to be -21.3 mmol/L. Partial small bowel resection, including ruptured aneurysmal area, was performed. Anastomoses were avoided, due to hemodynamic and metabolic instability; loops of small intestine were exteriorized as end ileostomy. Three units of erythrocyte suspension were transfused peroperatively. Postoperatively, the patient was kept under observation in the intensive care unit, and transferred to service the next day. He was discharged from the hospital on postoperative 10th day. Microscopic examination of pathology specimen revealed recanalized thrombotic vascular structures in the mesenteric fatty tissue near the ruptured aneurysm. There were no signs indicating vasculitis. Stoma closure was performed second month postoperatively. At follow-up 6 months after surgery, the patient had no complications.

DISCUSSION VAA is very rare among vascular pathologies, but reported incidence has increased in recent years due to frequent use of imaging methods.[1] In autopsy series and angiographic studies it has been said to be 0.1% to 0.2%.[2] Among cases of VAA, 3% are SMA terminal branch aneurysm. Aneurysm is most commonly seen in the jejunal artery, followed by middle colic artery and ileal artery.[3,4] Most common causes are atherosclerosis, angiodysplasia, arteritis, and infection.[3,5] Grotemeyer et al. reported in their study that 39.1% of VAAs are diagnosed incidentally, 60.9% of VAAs are symptomatic (abdominal pain, nausea, vomiting, jaundice, etc.), and 17.4% of VAAs cause hemorrhagic shock.[6] Due to very high mortality and morbidity associated with VAA, treatment of incidental cases is recommended even when asymptomatic.[7]

Figure 2. Coronal computed tomography angiography image of aneurysmal dilatation approximately 5 cm in diameter located distal to ileocolic artery.

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It has been reported in the literature that 22% of VAAs are diagnosed after rupture.[8] Risk of rupture is higher in pregnant women, patients who have many aneurysms, if aneurysm has diameter of more than 2 cm, and in symptomatic patients.[9â&#x20AC;&#x201C;11] VAA is treated with surgery or endovascular intervention. Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

Bayraktar et al. A rare cause of hemoperitoneum: A case report of ruptured ileocolic artery aneurysm

Due to high probability of SMA terminal branch aneurysm rupture and end-organ damage, surgical treatment is usually preferred in these cases. Ligation of aneurysm and bowel resection procedure defined by Cooley and De Bakey in 1953 is still treatment of choice in surgery today.[12] Endovascular treatment can be attempted in patients who had previous abdominal surgery or in patients with multiple comorbidities.[13] This treatment can be used in ruptured aneurysm[13] and in small asymptomatic aneurysm. Aneurysm embolization (coil, glue, etc.) or covered stenting can be performed endovascularly. However, if there is suspicion of mycotic infection as etiology, high risk of infection of graft material should be considered.[10,14] Endovascular treatment can be performed in these cases with low rate of mortality and morbidity; however, many aneurysms may not be suitable for this treatment. Furthermore, experienced staff and angiography units with proper technical infrastructure are needed for endovascular treatment, and such facilities are available in only limited number of hospitals. Mortality rate due to ruptured aneurysm ranges from 8.5% to 75%.[8] Our patient was diagnosed with abdominal pain, and endovascular intervention was planned, but emergent surgery became necessary due to rupture of aneurysm. We believe that the fact that the rupture occurred in hospital conditions prevented mortality in this instance. Anastomosis was avoided because the patient was in hemorrhagic shock. Small bowel loops had severe edema due to resuscitation with intravenous fluid in a short time. This case illustrates that terminal branch aneurysm of SMA can rupture at any time. Therefore, performing treatment as soon as it is diagnosed may reduce mortality and morbidity. VAA is rare among vascular pathologies. Most cases are asymptomatic. VAA is often detected only once complications or symptoms arise, or incidentally, when imaging is performed for another reason. Once SMA terminal branch aneurysm is diagnosed, treatment is recommended as soon as possible due to high mortality and morbidity of complications. Even though endovascular treatment can be performed in selected cases, surgical treatment is preferred due to possibility of rupture and end-organ damage.

Conflict of interest: None declared.

REFERENCES 1. Sachdev-Ost U. Visceral artery aneurysms: review of current management options. Mt Sinai J Med 2010;77:296–303. 2. Tulsyan N, Kashyap VS, Greenberg RK, Sarac TP, Clair DG, Pierce G, et al. The endovascular management of visceral artery aneurysms and pseudoaneurysms. J Vasc Surg 2007;45:276–83. 3. Silva MB, Choi L, Cheng CC. Peripheral arterial occlusive disease. In: Townsend C, Beauchamp D, Evers M, Mattox K, editors. Sabistan. Textbook of Surgery. 19th ed. Philadelphia: WB Saunders; 2012. pp. 1725–84. 4. Maisonnette F, Thognon P, Durand-Fontanier S, Valleix D, Lachachi F, Descottes B. Rupture of mesenteric artery branch aneurysm. Ann Vasc Surg 2001;15:684–6. 5. Kurdal AT, Cerrahoglu M, Iskesen I, Sirin H. Superior mesenteric artery branch--jejunal artery aneurysm. Interact Cardiovasc Thorac Surg 2010;11:859–61. 6. Grotemeyer D, Duran M, Park EJ, Hoffmann N, Blondin D, Iskandar F, et al. Visceral artery aneurysms--follow-up of 23 patients with 31 aneurysms after surgical or interventional therapy. Langenbecks Arch Surg 2009;394:1093–100. 7. Horton KM, Smith C, Fishman EK. MDCT and 3D CT angiography of splanchnic artery aneurysms. AJR Am J Roentgenol 2007;189:641–7. 8. Chiesa R, Astore D, Guzzo G, Frigerio S, Tshomba Y, Castellano R, et al. Visceral artery aneurysms. Ann Vasc Surg 2005;19:42–8. 9. Wagner WH, Allins AD, Treiman RL, Cohen JL, Foran RF, Levin PM, et al. Ruptured visceral artery aneurysms. Ann Vasc Surg 1997;11:342– 7. 10. Sachdev U, Baril DT, Ellozy SH, Lookstein RA, Silverberg D, Jacobs TS, et al. Management of aneurysms involving branches of the celiac and superior mesenteric arteries: a comparison of surgical and endovascular therapy. J Vasc Surg 2006;44:718–24. 11. Carmeci C, McClenathan J. Visceral artery aneurysms as seen in a community hospital. Am J Surg 2000;179:486–9. 12. De Bakey ME, Cooley DA. Successful resection of mycotic aneurysm of superior mesenteric artery; case report and review of literature. Am Surg 1953;19:202–12. 13. Mendonça CT, Weingartner J, de Carvalho CA, Costa DS. Endovascular treatment of contained rupture of a superior mesenteric artery aneurysm resulting from neurofibromatosis type I. J Vasc Surg 2010;51:461–4. 14. Gabelmann A, Görich J, Merkle EM. Endovascular treatment of visceral artery aneurysms. J Endovasc Ther 2002;9:38–47.

OLGU SUNUMU - ÖZET

Nadir görülen bir hemoperitonium nedeni: İleokolik arter anevrizma rüptürü olgu sunumu Dr. Adem Bayraktar, Dr. Kaan Gök, Dr. Fatih Yanar, Dr. Bahar Canbay Torun, Dr. Cemalettin Ertekin İstanbul Üniversitesi İstanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

Visseral arter anevrizmaları (VAA) vasküler patolojiler arasında çok nadir görülmektedir. Otopsi çalışmalarında görülme sıklığı %0.1–%0.2 arasında değişmektedir. Çoğu olguda semptomsuzdurlar ve komplikasyonları sonucu tanı alırlar ya da başka nedenle yapılan görüntülemeler sırasında insidental olarak saptanırlar. Visseral arter anevrizmaları arasında süperiyor mezenterik arter (SMA) uç dal anevrizmaları %3 oranında görülmektedir. Anevrizma rüptürü sonucu intra ve/veya ekstraperitoneal kanamalar hayatı tehdit etmekte ve acil müdahale gerektirmektedir. Bu nedenle tanı konulduktan sonra hızlı bir şeklide cerrahi ya da endovasküler girişim ile tedavi edilmeleri gerekmektedir. Bu yazıda, karın ağrısı, bulantı, kusma nedeni ile başvuran ve görüntülemelerinde ileokolik arterde anevrizma saptanıp endovasküler girişim planlandığı ve hastanede yatış sırasında rüptüre olan, acil cerrahi girişim uygulanan olguyu sunmayı ve literatür taraması yapmayı amaçladık. Anahtar sözcükler: Akut karın; anevrizma rüptürü; vasküler anevrizma. Ulus Travma Acil Cerrahi Derg 2017;23(4):351–353

doi: 10.5505/tjtes.2016.08095

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Successful endoscopic treatment of an unusual foreign body in the stomach: A package of heroin Mehmet Asıl, M.D., Ramazan Dertli, M.D. Department of Gastroenterology, Necmettin Erbakan University Meram Faculty of Medicine, Konya-Turkey

ABSTRACT Drug addiction is an important medical and social problem. “Body packing” is frequently used for concealed transportation of illegal drugs. The drug is packed in small plastic packages and swallowed or placed into body cavities, such as the rectum or the vagina. Another aspect is “body stuffing,” in which the drug package is usually hastily swallowed in order to avoid arrest. Presently described is case of a body stuffer who ingested a package of heroin and was successfully treated with upper gastrointestinal endoscopy. Upper gastrointestinal endoscopy is a safe alternative therapeutic option in body stuffers in selected cases. Keywords: Body stuffer; foreign body; heroin; upper gastrointestinal system endoscopy.

INTRODUCTION Drug addiction is an important medical and social problem. Increasing trends of illicit drug use worldwide make it worthy of attention. Since marketing of such drugs is illegal, so-called “body packing” is frequently used for concealed transportation.[1] The drug is usually packed in small plastic packages and swallowed or placed into body cavity, such as the rectum or the vagina, by “drug mules” to transport the hidden material. Another aspect is “body stuffing,” in which the drug package is usually hastily swallowed to avoid arrest.[2] Several complications, such as disruption of the packing material and acute intoxication due to high dose drug exposure, intestinal obstruction or perforation, or airway obstruction have been reported in body packers and body stuffers in the literature. [3] Surgery is mainstay of treatment for swallowed drug packages, particularly when drug leak and intoxication is the problem. Endoscopic removal of ingested drug packages from the stomach is also a therapeutic option, but it has rarely been reported in the literature. To our knowledge, there are only Address for correspondence: Mehmet Asıl, M.D. Necmettin Erbakan Üniversitesi Tıp Fakültesi Hastanesi, Gastroenteroloji Kliniği, Konya, Turkey Tel: +90 332 - 223 65 17 E-mail: drmehmetasil@yahoo.com.tr Submitted: 24.02.2016 Accepted: 10.11.2016

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4 cases published in the English-language literature describing endoscopic retrieval of drug packages.[4–7] Presently described is case of a body stuffer who ingested a package of heroin and was treated with upper gastrointestinal endoscopy (UGIE).

CASE REPORT A 29-year-old male patient was admitted to the emergency department accompanied by police and claimed to have ingested a handmade plastic package containing heroin approximately 2 hours prior to hospital arrival. He was a local drug dealer, and he stated that he ingested the heroin package on purpose in effort to destroy the evidence and avoid arrest in police raid. He didn’t know exact quantity of heroin in the package, but stated that packaging of the drug had been sloppy. The heroin was wrapped in cigarette foil paper and then wrapped in plastic and taped loosely. Due to poor packaging, he was anxious about leak of contents and asked for package to be removed. He had no complaints on admission and seemed to be in good health. His blood pressure was 120/72 mmHg, heart rate 78/ min, temperature 36.8°C, and respiration was 12/min. Remainder of physical examination was also unremarkable. On admission, complete blood count, routine serum chemistries, including renal and liver functions, and serum electrolytes were all normal. Blood and urine toxicological tests were also found to be negative. Plain radiogram of the abdomen was obtained, but the package could not be visualized. The patient was informed about possible complications of the ingested heroin package and treatment options were discussed. Possible complications associated with upper gastrointestinal endoscopy, foreign body retrieval, and particularly Ulus Travma Acil Cerrahi Derg, July 2017, Vol. 23, No. 4

AsÄąl et al. Successful endoscopic treatment of an unusual foreign body in the stomach

risk of rupture of the package during endoscopic removal were also explained to the patient and informed consent was obtained. Endoscopy was performed with topical pharynx anesthesia under conscious sedation. Endoscopic examination revealed presence of grayish-colored plastic package approximately 5x3x1.5 cm in size lying in mid corpus (Fig. 1) in the stomach. Package appeared to be intact and undisrupted. It was caught with netted snare and withdrawn together with the endoscope without difficulty. After retrieval, the package was examined for any possible sign of disruption and it was found to be intact without any sign of spillage of the contents (Fig. 2). The patient was hospitalized for 24 hours for observation and discharged into police custody.

DISCUSSION Body packing and body stuffing are 2 closely related entities in which illicit drugs are swallowed. The first report describing a body packer was published in 1975.[8] There are several reports in the literature describing complications and management of such cases. There are several reports of cocaine having been body packed, and lethal cases of cocaine intoxication due to disruption of the packages have also been also reported. Ingestion of packages of heroin has also been reported. Naloxone is used in case of heroin toxicity. [9] Surgery is usually preferred for treatment of patients with signs of intoxication, whereas management of asymptomatic body packers is usually conservative.[10] Most packages pass spontaneously in stools, although stool softener may be used to facilitate excretion. In case of intestinal obstruction, or when progression of package through the intestines

stops, surgery is again the mainstay of treatment since risk of package rupture increases with time. UGIE and colonoscopy are other therapeutic options. Packages that have not passed beyond the pylorus can be retrieved using UGIE. There are only a few reports in the literature describing retrieval of packed drugs with UGIE. We believe that this is primarily because length of time in police custody after swallowing the package in an asymptomatic body packer, or until occurrence of symptoms in complicated case, allows for passage of the drugs far beyond the pylorus. Secondly, disruption of the package and spillage of contents during endoscopic retrieval is another concern limiting use of UGIE in these patients. Particularly in case where numerous packages have been swallowed, endoscopic retrieval of all packages without disruption may be difficult. Yet there are case reports in the literature that describe successful endoscopic removal of drug packages. In our case, since the patient had swallowed only single package of heroin and he had been brought to the hospital immediately, length of time from swallowing to endoscopic intervention was short. Package was still in the stomach, allowing for endoscopic retrieval without complication. Although the patient was asymptomatic, conservative management was not planned because the patient had stated that the packaging was poorly done; therefore, there was greater risk of drug leakage and subsequent opiate intoxication. Moreover, there was strong patient will to have package removed. Surgery and endoscopy were offered as potential therapeutic interventions. The patient declined surgery. Endoscopy was performed and the package was successfully removed.[11] In our case, endoscopic treatment was successful and without complication. Possible complications associated with endoscopic foreign body retrieval include perforation, hemorrhage, foreign body impaction, airway obstruction, and sedoanalgesia-related complications. In cases of body packers and body stuffers, particularly disruption of drug packages and spillage of contents during endoscopic retrieval with subsequent drug intoxication is a major concern. Therefore, maximal care should be taken during endoscopic intervention and retrieved packages should be carefully examined after withdrawal from the body for any sign of disruption.

Figure 1. Heroin package observed in the stomach.

Figure 2. Retrieved heroin package.

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Another noteworthy point is that although plain radiogram of the abdomen was obtained at the time of admission, the package couldnâ&#x20AC;&#x2122;t be visualized. Reported sensitivity of conventional radiograms in detecting drug packages ranges from 40% to 90%.[12] Therefore, when plain radiogram is normal, further radiological studies, such as abdominal ultrasound, computerized tomography, or contrast passage radiograms should also be performed in suspicious cases. One last point to mention is that although blood and urine toxicological tests were performed, they were all found to be negative. In asymptomatic body packers, diagnostic value of blood and urine toxicological tests is low, since in most cases 355

Asıl et al. Successful endoscopic treatment of an unusual foreign body in the stomach

the packages remain intact. Therefore, such tests should not be used alone for screening purposes in suspected cases. In conclusion, management of body packer and body stuffer cases is still challenging sometimes. Although surgery is the preferred method of treatment in symptomatic cases, UGIE can be considered a minimally invasive therapeutic procedure that may be suitable in selected cases with no signs of toxicity, when elapsed time between swallowing and hospital arrival is short, and number of swallowed packages is small. Conflict of interest: None declared.

REFERENCES 1. Traub SJ, Hoffman RS, Nelson LS. Body packing--the internal concealment of illicit drugs. N Engl J Med 2003;349:2519–26. 2. Roberts JR, Price D, Goldfrank L, Hartnett L. The bodystuffer syndrome: a clandestine form of drug overdose. Am J Emerg Med 1986;4:24–7. 3. Kocakuşak A, Yücel AF, Arikan S, Gülen M, Koyuncu A, Asici B, et al. Clinical follow-up of patients who ingested narcotic filled bags as a rare cause of mechanical bowel obstruction: case report. Ulus Travma Acil

Cerrahi Derg 2003;9:209–11. 4. Sherman A, Zingler BM. Successful endoscopic retrieval of a cocaine packet from the stomach. Gastrointest Endosc 1990;36:152–4. 5. Choudhary AM, Taubin H, Gupta T, Roberts I. Endoscopic removal of a cocaine packet from the stomach. J Clin Gastroenterol 1998;27:155–6. 6. Macedo G, Ribeiro T. Esophageal obstruction and endoscopic removal of a cocaine packet. Am J Gastroenterol 2001;96:1656–7. 7. Coelho R, Orfao B, Macedo G. Successful endoscopic removal of a cocaine capsule in the stomach: should it be considered a safe therapeutic option? Endoscopy 2014;46 Suppl 1:579–80. 8. Deitel M, Syed AK. Intestinal obstruction by an unusual foreign body. Can Med Assoc J 1973;109:211–2. 9. Boyer EW. Management of opioid analgesic overdose. N Engl J Med 2012;367:146–55. 10. Booker RJ, Smith JE, Rodger MP. Packers, pushers and stuffers--managing patients with concealed drugs in UK emergency departments: a clinical and medicolegal review. Emerg Med J 2009;26:316–20. 11. Berger FH, Nieboer KH, Goh GS, Pinto A, Scaglione M. Body packing: a review of general background, clinical and imaging aspects. Radiol Med 2015;120:118–32. 12. Pinto A, Reginelli A, Pinto F, Sica G, Scaglione M, Berger FH, et al. Radiological and practical aspects of body packing. Br J Radiol 2014;87:20130500.

OLGU SUNUMU - ÖZET

Midede olağandışı bir yabancı cismin başarılı olarak endoskopik yöntemle tedavisi: Bir eroin paketi Dr. Mehmet Asıl, Dr. Ramazan Dertli Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Gastroenteroloji Bilim Dalı, Konya

İlaç bağımlılığı önemli bir sosyal ve tıbbi sorundur. Uyuşturucu madde kaçakçılığında “vücutta depolama” yöntemi sıklıkla kullanılmaktadır. Uyuşturucu madde küçük plastik paketler halinde hazırlandıktan sonra yutulur ya da rektum, vajina gibi doğal vücut kavitelerine yerleştirilir. Diğer benzer bir durum da uyuşturucu madde paketinin polis baskını sırasında tutuklanmamak için istemli yutulmasıdır. Biz burada eroin içeren bir paket yutan ve endoskopik olarak tedavi edilen bir olguyu sunduk. “Vücut Depolayıcıları”nın yuttuğu uyuşturucu paketlerinin tedavisinde, uygun olgularda üst gastrointestinal endoskopi güvenli bir alternatif yöntemdir. Anahtar sözcükler: Eroin; üst gastrointestinal endoskopi; vücut depolayıcısı; yabancı cisim. Ulus Travma Acil Cerrahi Derg 2017;23(4):354–356

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doi: 10.5505/tjtes.2017.93462

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