TJTES 2020-6 by KAREPUBLISHING

ISSN 1306 - 696X

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

Volume 26 | Number 6 | November 2020

www.tjtes.org

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

www.tjtes.org

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

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

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

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

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

KARE P U B L I S H I N G

www.tjtes.org

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

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

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

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

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

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

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

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

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

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

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

Number - Sayı 6 November - Kasım 2020

Contents - İçindekiler Experimental Studies - Deneysel Çalışma 833-842 Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic Geçici mekanik obstrüksiyona maruz kalmış, probiyotik ile beslenen sıçanlarda bağırsak mukozası Edizsoy A, Yılmaz E, Çevikel MH, Yenisey Ç, Sakarya S, Meteoğlu İ 843-846 The protective role of probiotics in sepsis-induced rats Sepsis oluşturulan sıçanlarda probiotiklerin koruyucu rolü Yılmaz M, Erdem AO 847-852 Ameliorating the effects of Adalimumab on rabbits with experimental cerebral vasospasm after subarachnoid hemorrhage Adalimumab’ın tavşanlarda deneysel subaraknoid kanama sonrası oluşan serebral vazospasm üzerine iyileştirici etkileri Toğuşlu G, Erdi MF, Araç D, Keskin F, Kılınç İ, Cüce G 853-858 Effects of Algan Hemostatic Agent on bleeding time in a rat tail hemorrhage model Algan Hemostatik Ajan’ın sıçan kuyruk kanama modelinde kanama zamanı üzerine etkisi Gedar Totuk ÖM, Güzel ŞE, Ekici H, Kumandaş A, Emre Aydıngöz S, Yılmaz EÇ, Kırdan T, Midi A

Original Articles - Orijinal Çalışma 859-864 Prognostic factors in craniocerebral gunshot wounds: Analysis of 30 patients from the neurosurgical viewpoint Kranioserebral ateşli silah yaralanmalarında prognostik faktörler: Nöroşirürjikal bakış açısından 30 hastanın analizi Kırık A, Yaşar S, Durmaz MO 865-869 Evaluation of complications in patients with open fractures of the upper and lower extremity treated with internal fixation after the external fixation Alt ve üst ekstremitenin açık kırıklarında eksternal fiksatör uygulanmış internal fiksasyona geçilen olgularda komplikasyonların değerlendirilmesi Bilir M, Tekin SB 870-874 Older patients with intraventricular hemorrhage are prone to infection after external ventricular drainage Yaşlı ve intraventriküler kanaması olan hastalar eksternal ventrikül drenajı sonrası enfeksiyona daha yatkındır Yaşar S, Kırık A 875-882 Does a selective surgical approach to malignant bowel obstruction help in palliative care patients? Palyatif bakım hastalarında görülen malign bağırsak obstrüksiyonlarında selektif cerrahi yaklaşım fayda sağlıyor mu? Akbaş A, Daldal E, Daşıran F, Bakır H, Dagmura H, Okan İ 883-886 Does primer appendagitis epiploica require surgical intervention? Primer appendagitis epiploica da cerrahi müdahale gerektirir mi? Mantoğlu B, Altıntoprak F, Akın E, Fırat N, Gönüllü E, Dikicier E 887-892 The evaluation of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in anorectal abscess Anorektal apsede nötrofil lenfosit oranı ve trombosit lenfosit oranının değerlendirilmesi Akalın Ç 893-898 APACHE II or INCNS to predict mortality in traumatic brain injury: A retrospective cohort study Travmatik beyin hasarında mortaliteyi tahmin etmede APACHE II mi INCNS mi?: Geriye dönük kohort çalışma Gürsoy G, Gürsoy C, Kuşcu Y, Gümüş Demirbilek S 899-904 High-pressure injection injuries to the upper extremity and the review of the literature Üst ekstremitenin yüksek basınçlı enjeksiyon yaralanmaları ve literatürün gözden geçirilmesi Yıldıran G, Sütçü M, Akdağ O, Tosun Z 905-910 The association between injury severity and psychological morbidity, hand function, and return to work in traumatic hand injury with major nerve involvement: A one-year follow-up study Majör sinir tutulumu olan travmatik el yaralanmalarında yaralanma şiddeti ile psikolojik morbidite, el fonksiyonu ve işe dönüş arasındaki ilişki: Bir yıllık takip çalışması Tezel N, Can A Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

vii

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

Number - Sayı 6 November - Kasım 2020

Contents - İçindekiler 911-919 The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds Seken av tüfeği saçma tanesi yaralanmalarının analizi ve atışın yeniden yapılandırılması Öğünç Gİ, Özer MT, Uzar Aİ, Eryılmaz M, Mercan M 920-926 Evaluation of the Nexus X-ray rules in blunt thorax trauma Künt toraks travmasında Nexus X-ray kurallarının değerlendirilmesi Acar E, Demir A, Yıldırım B, Kaya G, Alataş ÖD, Kılınç RM, Zeybek A, Özkaraca O 927-931 A different approach to leakage of esophageal atresia in children Çocuklarda özofagus atrezisi kaçaklarına farklı bir yaklaşım Basuguy E, Okur MH, Arslan S, Zeytun H, Aydoğdu B 932-936 Different approaches in diagnosis, follow-up and treatment of acute biliary pancreatitis: Results of attitude survey Akut biliyer pankreatit tanısında, izleminde ve tedavisinde farklı yaklaşımlar: Tutum anketi sonuçları Somuncu E, Sarıcı İŞ, Kızılkaya MC, Kara Y, Sarıgöz T, Sevim Y, Altıntaş T, Diri M, Yıldız BZ, Gökay R, Özkan C, Sıbıç O, Özcan A, Basaran C, Kalaycı MU 937-942 Analysis of anatomical localization and severity of injury in patients with blood transfusion in urban terrain hospital Saha hastanesinde kan transfüzyonu uygulanan hastalarda yaralanma şiddeti ve anatomik lokalizasyonunun analizi Eksert S, Ünlü A, Aydın FN, Kaya M, Aşık MB, Kantemir A, Öztaş M, Keklikci K, Sir E 943-950 The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations Ayak bileği kırıklı çıkıklarında cerrahi tedavisi sonrası zayıf klinik sonuçlara yol açan yaygın komorbiditeler Yalın M, Aslantaş FÇ, Duramaz A, Bilgili MG, Baca E, Koluman A

Case Reports - Olgu Sunumu 951-954 Pancreatic cystic Echinococcosis causing acute pancreatitis Akut pankreatite neden olan pankreas kistik ekinokokkozisi Destek S, Değer KC 955-959 Free perforation of primary small bowel lymphoma in a patient with celiac sprue and dermatitis herpetiformis Çölyak hastalığı ve dermatitis herpetiformisi olan bir hastada primer ince bağırsak lenfomasının serbest perforasyonu Bolat H, Teke Z 960-962 Fat embolism syndrome after gluteal augmentation with hyaluronic acid: A case report Hyalüronik asit ile kalça dolgusu sonrası yağ emboli sendromu olgusu Uz İ, Yalçınlı S, Efe M

viii

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

EXPERIMENTAL STUDY

Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic Akay Edizsoy, M.D.,1 Eyüp Yılmaz, M.D.,2 Mehmet Hakan Çevikel, M.D.,2 Çiğdem Yenisey, M.D.,3 Serhan Sakarya, M.D.,4 İbrahim Meteoğlu, M.D.5 1

Departmant of General Surgery, Surgical Oncology, Mersin University Faculty of Medicine, Mersin-Turkey

Departmant of General Surgery, Adnan Menderes University Faculty of Medicine, Aydın-Turkey

Departmant of Biochemistry, Adnan Menderes University Faculty of Medicine, Aydın-Turkey

Departmant of Infectious Diseases, Adnan Menderes University Faculty of Medicine, Aydın-Turkey

Departmant of Pathology, Adnan Menderes University Faculty of Medicine, Aydın-Turkey

ABSTRACT BACKGROUND: Created a model in the rats, to prevent mucosal damage and related effects in the patients, who were operated due to mechanical obstruction. Some groups fed fodder with probiotics, some groups fed with standard fodder. It is objected that the damage of gut mucosa and related effects on how to expose the differences of the groups. METHODS: In this study, 48 female Wistar-albino type rats are separated into five groups randomly. In the first operation, rats’ terminal ileum was tied up with silk except for the control group. Two groups 24, the other two groups 48 hours later operated again and terminal ileum obstructions were removed. During that time, each one of those 24 and 48 hours of obstructed groups were fed with probiotic. Twenty-four hours later, the control group and other groups were operated for the third time for sampling. Terminal ileum, liver, spleen, MLN (Mesenteric lymph node) and blood samples were taken. RESULTS: The research group, which was obstructed and fed with probiotics during 48 hours, was significantly observed in increased mucosa cell loss and mucosal edema. Bacterial translocation was found more common in groups without probiotics. Tissue GR (Glutathione reductase) and erythrocyte CAT (Catalase) were lower in the group of 24 hours obstructed and given probiotics. CONCLUSION: The findings suggest that the high rate of mucosal edemas in the groups that are fed with probiotics can be seen as damage, but we think that probiotics are consonant with the strength of the mucosal barrier. Thus, in the groups fed with probiotics, it is possible that bacterial translocation is seen less, and some antioxidative enzymes are found less. Further studies are needed to investigate the benefits of probiotics in patients operated for obstruction. Keywords: Antioxidative enzyme; bacterial translocation; mucosal damage; obstruction; probiotic.

INTRODUCTION Mechanical ileus is an important cause of morbidity and mortality worldwide. When surgical treatment of the mechanical ileus is initiated, the obstruction disappears, but the symptoms do not regress immediately. Some complications may occur despite the operation. Perforation due to intestinal mucosal damage, bacterial translocation and sepsis are some of them, which can be life-threatening complications. In this

study, our aim is to observe if there is any benefit of probiotic use in preventing or reducing complications, such as perforation, bacterial translocation and sepsis, due to intestinal mucosal damage, which may occur in the postoperative period. The obstruction of the intestinal lumen is due to a complete or partial pathological lesion. This situation, wall, lumen inside and lumen may be due to external pressure. If there is a blockage in patients who have undergone intra-abdominal

Cite this article as: Edizsoy A, Yılmaz E, Çevikel MH, Yenisey Ç, Sakarya S, Meteoğlu İ. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic. Ulus Travma Acil Cerrahi Derg 2020;26:833-842. Address for correspondence: Akay Edizsoy, M.D. Mersin Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Cerrahi Onkoloji, Mersin, Turkey Tel: +90 324 - 241 00 00 E-mail: akayedizsoy@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(6):833-842 DOI: 10.14744/tjtes.2020.30269 Submitted: 30.09.2019 Accepted: 12.01.2020 Online: 21.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

833

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

surgery, the reason is that they are approximately 60–80% brid, 15–20% of hernia, lumen or external tumors 15–20% of the etiology takes place.[1] Mechanical ileus metabolic effects occur because of fluid loss. The level and duration of obstruction are important. The damage of the mucosa causes intestinal flora to pass into the mesenteric lymph nodes (MLN), spleen, liver and systemic circulation, which is called a bacterial translocation (BT). Local defense mechanisms provide stabilization of the intestinal flora. The first step of the barrier function is intestinal microflora. The proliferation and adhesion of pathogenic bacteria, the inhibition of bacteria in the flora, is called colonization resistance.[2] Reduction of immune defense, hunger, burn, trauma, surgical stress, and overproliferation of intestinal flora bacteria increased permeability of intestinal mucosa, cholestasis. BT has been shown to be associated with excessive proliferation of bacteria in the lumen of the intestine.[3] Molecules working in advanced defense systems to prevent damage that arise from free radicals are called antioxidants. In humans, the antioxidative capacity in serum is associated with enzymatic and non-the enzymatic system. They can be endogenous and exogenous. Endogenous ones are divided into two according to whether the enzyme. Enzymes are superoxide dismutase (SOD), glutathione-S-transferases (GST), catalase (CAT), glutathione peroxidase (GSH-Px). There are approximately 1013 cells in the human body. There are 1014 bacteria living with us in our bodies. This microbiota, which is more than the host’s own cells, plays an active role at many points in the functioning of the metabolism.[4] The most intense area is the gastrointestinal system.[5] The microorganisms are in close contact with the intestinal mucosa of approximately 250–400 m2 area. Stomach contains 104, duodenum 103–104, jejunum 105–107, ileum 107–108, colon 1010–1011 CFU/g probiotic bacteria. The mucosal defense system, which contributes to the immune system, works in conjunction with the intestinal flora.[6] Effect mechanisms,, competitive metabolic interaction with pathogens preparation of chemical products that inhibit bacteria and viruses (bacteriocins) by creating other chemicals, such as neurotransmitters, regulating other intestinal functions, such as sensitivity, susceptibility to bacterial movement (BT) inhibition in bowel wall. Mucosal barrier function enhancement mucine expression with the epithelial barrier function is the effect of cytoskeleton proteins and tight associations, such as inflammatory and immune response regulation, by indirectly affecting or indirectly causing interaction between the bacterial-mucosa and mucosal-lymphoid tissue.[7] The mechanisms of action can be divided into two as indirect effects and directly affects: 834

Direct effects: Mucosal and luminal effects. Mucosal effects: Cytokine response is on cell signal transduction and receptors. Luminal effects: Mucus production, destruction and antagonism in the intestinal flora, competition for receptors and nutrients, butyrate production. Indirect effects: Immunostaining, anti-infective effect, antidiarrheal effect and effects on intestinal transit. Bifidobacterium animalis: Provides normal motility. Reduces the risk of acute diarrhea. It is used in irritable bowel syndrome.[8]

MATERIALS AND METHODS This experimental study was conducted in Adnan Menderes University Laboratory of Experimental Animals in July 2015 with the approval of the Local Ethics Committee of Animal Experiments (64583101/2015/037). In all phases of this study, the local ethics committee’s instructions dated 16 June 2009 were followed. In this study, 48 female Wistar-albino rats weighing 200–250 grams were used in the experimental animals laboratory of Adnan Menderes University Medical Faculty. During the experiment, rats were maintained at 22±2 ºC ambient temperature, 12/12 hours light/dark cycle, relative humidity (40-50%) and aerated air controlled laboratory conditions. All animals were free to eat and drink water until 8–12 hours before the experiment. Before surgery, rats were kept in the laboratory for one week to get used to. Rats were fed with standard rat forage and tap water in polycarbonate transparent lattices. Wistar-albino rats were randomly divided into five groups: Group A: Sham group; no obstruction, only laparotomy (n=8) Group B: P (-)24. 24 hours of obstruction, but not given probiotic (n=10) Group C: P (-)48. 48 hours of obstruction but not given probiotic (n=10) Group D: P (+)24. 24 hours of obstruction and probiotic administration (n=10) Group E: P (+)48. 48 hours of obstruction and probiotic administration (n=10) After one week of follow-up, 50 mg/kg ketamine (Alfamin®; Egevet Tic. Ltd. Sti.) and 5 mg/kg xylazine (Alfazin®; Egevet Tic. Ltd. Sti.) were administered intraperitoneally (Fig. 1a). After cleaning the skin of the abdomen, povidone-iodine was Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

(a)

(e)

(b)

(c)

(d)

(f)

(g)

Figure 1. (a) Anesthesia, (b) shaving, (c) prepare to operation, (d) creation of mechanical obstruction, (e) abdominal closure, (f) skin closure, (g) dressing.

applied to the skin (Fig. 1b). Covered sterile and laparotomy was performed with a midline incision of approximately 3 cm (Fig. 1c). In groups other than group A, the ceacum was found and was ligated at 1 cm proximal terminal ileum, with 3/0 silk (Sterisilk®). While the ligation was performed, mechanical obstruction was formed by preventing only the passage of the bowel without causing ischemia (Fig. 1d). Then, the abdomen was closed with a double layer with 4/0 propyprolen (Prolene®) (Fig. 1e, f ). No other procedure was performed except laparotomy and closure of the abdomen to the subjects in group A.[9]

(a)

(b)

After the operation, subjects were allowed to drink water and feed. The subjects in group D and E were administered either 1 mg/kg/day (1x10 CFU/mg) probiotic (Bifidobacterium animalis spp lactis B94, MAFLOR®) by orogastric gavage (Fig. 2a). At the end of 24 hours, B and D groups were reoperated, the obstruction was removed by opening the ligation in the terminal ileum, and the subjects in group D and E continued to be administered the same dose of probiotic. After 48 hours, group C and E were reoperated, the obstruction was removed by opening the ligation in the terminal ileum, and the subjects in group E continued to be administered the

(c)

Figure 2. (a) Orogastric gavage feding, (b) remove obtruction, (c) terminal ileum after obstruction is removed.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

835

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

(a)

belonged to the pathology laboratory. The liver, spleen and mesentery samples were placed in sterile falcon tubes containing 0.09% NaCl and delivered to the Infectious Diseases laboratory in cold (-21 ºC) storage containers. Intracardiac blood samples were placed in biochemistry tubes and transported to biochemistry laboratory in cold containers (-4 ºC).

(b)

Figure 3. (a) Microbiologic sampling of spleen, (b) sampling of terminal ileum.

same dose of probiotic. Group A subjects underwent laparotomy twice, but no obstruction was performed. It was observed that small bowel loops were dilated proximal to the obstruction before opening the ligation in the terminal ileum (Fig. 2b). One subject in group B and one subject in group C were ex after the second operations. Twenty-four hours after the second operation, all groups were operated for the third time. These operations were to obtain microbiological tissue samples from liver, spleen and mesentery, histopathological and biochemical tissue samples from the terminal ileum, biochemical samples from intracardiac blood, respectively (Fig. 3a, b). The subjects were sacrificed with cardiac collapse by intracardiac blood collection. Terminal ileum samples were placed in sterile containers containing 10% formaldehyde. The numbers of the numbers

(a)

(d)

Some of the biochemical samples were a sample from group C and two from group E, which could not be included in this study because they were inadequate. In pathological examination, in 10% neutral buffered formalin, 4μm thick and hematoxylin eosin dyed preparations were prepared from blocks embedded in paraffin blocks after routine tissue monitoring were examined. After staining, sections were blinded to clinical information by a single pathologist at 4, 10, 20, and 40 magnifications under the light microscope (Olympus® BX51, Tokyo, Japan) (Fig. 4). For evaluation, the semi-quantitative mucosal damage score, as shown by Millar et al.,[10] was performed, as shown in the table below (Table 1). Blood samples were taken into the tubes used in routine biochemistry tests and after centrifugation at 4,000 rpm for 10 minutes, each sample was separated into two Eppendorf tubes and stored in the freezer (-85 °C) until experiments were performed.

(b)

(c)

(e)

Figure 4. Terminal ileum sections from different groups. (a) Group A, (b) group B, (c) group C, (d) group D, (e) group E.

836

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

Table 1. Histopathological assessment of terminal ileum resection specimens in rats Neutrophil infiltrate None 0 Slight increase 1 Marked increase 2 Epithelium (0–2) Lamina propria

(0–2)

Muscularis mucosa

(0–2)

Submucosa (0–2) Muscularis propria

(0–2)

Serosa (0–2) Fibrin deposition Absent 0 Present 1 Mucosa (0–1) Submucosa (0–1) Submucosal neutrophil margination Absent 0 Present 1

(0–1)

Submucosal edema Nil 0 Patchy 1 Confluent 2

(0–2)

Epithelial necrosis Nil 0 Localised 1 Extensive 2

(0–2)

Epithelial ulceration Absent 0 Present 1

(0–1)

Maximum score

Tissue samples were prepared as a protease inhibitor of 0.2 µM phenylmethanesulfonyl fluoride (PMSF), 1 µM Ethylenediaminetetraacetic acid (EDTA), 1 µM Leupeptin containing 50 µM phosphate buffer (pH 7.4) (1/10 g/ml) was homogenized in. The homogenates were centrifuged at 10,000 rpm for five minutes after the sample was separated for MPO (Myeloperoxidase), and the supernatant at the top was split equally into ependorf tube and frozen at -80 °C to allow further parameters to be checked. The erythrocytes and supernatants obtained from tissue samples were determined using the method of Aebi et al.[11] For CAT (Catalase), serum MDA (Malondialdehyde) was determined using Ohkowa’s method.[12] Results were given as µM. MDA values in tissue samples Konukoglu et al.[13] It

(a)

(b)

(c)

was measured in whole blood and tissue supernatant according to Tietze’s method for GSH (Glutathione).[14] GPx (Glutathione peroxidase) activity in erythrocytes measured according to the method of Pleban et al.[15] GPx activity in tissue supernatant was determined using Kakkar et al.’s[16] method by minor modification. GR (Glutathione reductase) activity in erythrocytes and tissue was determined using the method of Racker et al.[17] The measurement of SOD (Superoxide dismutase) in erythrocytes and tissue supernatants was determined according to the method of Sun et al.[18] NO (Nitric oxide) levels in serum, and tissue supernatant were determined according to the method of Navarro-Gonzálvez et al.[19] Under the sterile conditions, liver, spleen, and mesenteric lymph node specimens were previously placed in a 15 cc sterile falcon tubes each with sterile 2 cc 0.09% NaCl (Sodium chloride) added and numbered without group information. The groups to which the numbers belong were also recorded. The tubes were then homogenized by sonication. From the homogenized samples, 1 cc of the homogenized samples was taken into 2 cc Eppendorf tubes and then stored at -20ºC to measure the amount of protein they contained. After sowing culture containers were recorded with numbersof sample and incubated at 37 ºC for 24 hours. At the end of 24 hours, bacteria colonies were counted (Fig. 5). Frozen samples created by sonicator (Fig. 6a) in Eppendorf tubes were kept at 37 ºC for 30 minutes. The tubes were then centrifuged at 13300 rpm for five minutes. Protein measurement was performed using Bicinchoninic acid assay (BCA) method, as shown by Smith et al.[20] All samples were placed in the wells to be used in the spectrophotometer, including blind samples for the first row reset, and incubated at 37 ºC for 30 minutes (Fig. 6b, c). The results obtained in the spectrophotometer were then proportional to the number of colonies. These ratios were recorded as colony/1 mg protein for statistical purposes.

RESULTS The appropriateness of the quantitative data to the normal distribution was investigated using Kolmogorov Smirnov test.

(d)

(e)

Figure 5. Colonies from liver samples. (a) Group A, (b) Group B, (c) Group C, (d) Group D, (e) Group E.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

837

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

(a)

(b)

(c)

Figure 6. (a) Sonicator, (b) samples in wells, (c) spectrophotometer.

In microbiological variables, the difference in bacterial colonization rates of liver, spleen and mesentery was observed (Table 3). In the liver, bacteria were more colonized in group B than in group D (p<0.001). Test results showed that the bacteria colonized in group C were more than group A and E (Table 3), (Fig. 7). In the spleen colonized by bacteria in group B was more than group D (p<0.001) (Fig. 8). According to this, the maximum BT was seen in the group with 48 hours obstructed and not given probiotic (group C), while the least it was observed in the group with 24 hours obstructed and given probiotic (group B).

One-way analysis of variance (ANOVA) was used in statistical comparisons for the variables which were suitable for normal distribution and descriptive statistics were shown as mean±standard deviation. The Kruskal-Wallis test was used for statistical comparisons for variables not suitable for normal distribution and descriptive statistics were shown in the form of median (25–75 percentile). P<0.05 was considered statistically significant. During the experiment, two subjects from the C group could not be included in the statistical studies due to inadequate sampling for only biochemical test. A subject from the E group and a subject from the C group died after the second operation. Thus, they were excluded from statistical studies.

Biochemically, some differences were detected in tissue, serum and whole blood samples (Table 4). NO levels in group A were found to be higher than B, D and E groups (p<0.05) (Fig. 9). When erythrocyte catalase levels were measured in whole blood samples, group D groups were found to be less than groups A and B (p<0.005) (Fig. 10).

There were significant differences in mucosal damage scores between groups. Mucosal damage scores was lower in group A than in group E (p=0.023) (Table 2). Table 2. Anova test results applied to mucosal damage scores Group

Score

3.7500±1.58114

4.0000±1.73205

4.1111±1.76383

5.5000±1.26930

6.0000α±0.70711 0.023

α: Group E differed from groups A.

Table 3. Kruskal Wallis test results applied to bacterial translocation parameters Group

Liver 145.26 979.94α 1685.65β

32.65

29.29 <0.001

Spleen 76.255

1126.03

2166.4

3.155γ

41.29 <0.001

Mesentery 128.775

177.56

550.47

31.16

85.93

0.028

α: Group B differed from groups D. (B>D); β: Group C differed from groups A and E. (C>A>E); γ: Group D differed from groups B. (B>D).

838

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

2600

6000

2400 2200

5000

2000 1800

4000

1600 Spleen

Liver

1400 1200 1000

3000 2000

800 600

1000

400 200

0 -200

-1000

Figure 7. Median distribution of bacterial translocation rates to the liver (colony/1 mg protein). Group B differed from D and E groups. Group C differed from groups A, D and E (p<0.005).

Figure 8. Median distribution of bacterial translocation rates to the spleen (colony/1 mg protein). D group differed from B and C groups (p<0.05).

The differences between the groups in terms of Tissue GSH, Tissue SOD and Erythrocyte GR were not significant (Table 5).

In a study that examined the effects of probiotic nutrition in rats with radiation-induced mucosal damage, no difference was detected between the group given to the probiotic group and the control group and bacterial translocation to the liver, spleen and mesenteric lymph nodes separately.[22] In our study, mucosal damage was achieved by obstruction of 24 or 48 hours. The rate of bacterial colony in the liver was higher in the non-probiotic groups. The colonization rate in spleen samples from P (+)24 group was less than in P (-)24 group.

DISCUSSION The groups were given short names [B: P (-)24, C: P (-)48, D: P (+)24, E: P (+)48] according to probiotic administration and occlusion time. The samples were taken in the third operation. Lu et al.[21] studied the contribution of SOD to the development of ileal obstruction in rats and healing of mucosal damage. It was shown that the mucosal damage score increased in the groups with 24 hours of obstruction compared to the control group. In our study, it was shown that mucosal damage was higher in the obstruction group compared to the control group. However, mucosal damage score in the P (+)48 group was higher than in the control group. There was no significant difference in mucosal damage between the groups who had 24 or 48 hour obstruction with or without probiotic administration.

El-Awady et al.[23] performed a 28-hour study of rats with ileal obstruction and strangulated obstruction. In simple obstruction, tissue GPx and tissue MDA oxidative stress parameters were elevated. In our study, NO levels were higher in the control group than in the P (-)24, P (+)24 and P (+)48 groups. When erythrocyte catalase levels were measured, P (+)24 was found to be less than P (-)24 and control group.

Table 4. Kruskal Wallis test results applied to biochemical parameters Group Tissue GR

1012.5

797.872

1125

150

600

0.025

Tissue NO

1.068706 0.793412 0.8287055 0.962824 0.736941 0.328

Serum MDA

149.167 207.5 170.833 182.5 136.667 0.94

Serum NO

39.412α

14.018

23.655

11.3515

16.4425

<0.05

Erythrocyte SOD 177.477 181.745 186.04 200.052 198.486 0.324 Erythrocyte CAT

634.4115

718.46

569.126

420.161β 482.69 <0.05

Erythrocyte GSH 21.719 20.391 20.25 21.875 19.688 0.474 α: Group A differed from groups B, D and E; β: Group D differed from groups A and B. GR: Glutathione reductase; NO: Nitric oxide; MDA: Malondialdehyde; SOD: Superoxide dismutase; CAT: Catalase; GSH: Glutathione.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

839

0.689

0.742

0.221

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

40 30 20

21.04914±19.594817

SNO

236.59811±57.835436

517.65±275.870836

Figure 9. Median distribution of nitric oxide values measured in serum samples. Group A differed from B, D and E groups (p<0.005).

30.33522±28.488501

-10

547.23±169.11696

213.4646±60.079284

Aldemir et al.[24] administered intravenous octreotide acetate or a probiotic S. boulardii orogastric in rats treated with ileal loop obstruction, and bacterial translocation and villous width values were measured. S. boulardii and octreotide acetate groups were shown to be more villous and less bacterial translocation than untreated group. In our study, Bifidobacterium animalis spp lactis B94 was used as probiotic. In our study, vascular enlargement was evaluated as mucosal edema and an increase was observed in probiotic groups. Bacterial translocation was found to be decreased in the probiotic group. In our study, we showed a decrease in bacterial translocation in the groups in which we used Bifidobacterium animalis spp lactide B94. Similarly, Generoso et al.[25] showed differences using the Saccharomyces cerevisiae strain UFMG 905. In the 840

208.634±71.253955

37.17489±24.889926 α: Group A differed from groups B, D and E; β: Group D differed from groups A and B. GSH: Glutathione. SOD: Superoxide dismutase; GR: Glutathione reductase.

Figure 10. Median distribution of catalase values measured in erythrocyte extracted samples. D group differed from A, B and C groups (p<0.005).

27.11656±24.719380

240.30022±42.790973

35.97788±123.124073

228.89925±65.524658

Erythrocyt GR

Tissue SOD

200

775.04778±529.26135

400

600

Group

800

1000

Table 5. Anova test results applied to normal distribution biochemical parameters

ECAT

1200

804.7±230.382

1400

Tissue GSH

1600

728.56125±299.334101

1800

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic

same study, mucosal edema was detected histopathologically in the probiotic groups. In our study, mucosal edema increased in P (+)48 group compared to control group. In their study, Antequera et al.[26] compared bacterial translocation and mucosal damage at 24, 48, 72 hours in experimental rats with experimental intestinal obstruction. In the first 24 hours, they did not detect any significant change in mucosa epithelium. They showed a significant increase in vascular dilatation and mucosal edema after 48 hours. In our study, mucosal edema was found more in group P (+)48 than control group (p<0.05). This may be because probiotics increase mucosal edema. Mañé et al.[27] produced colitis in rats and gave them different probiotics. Samples were taken after 1–3 weeks. In this study, mucosal damage was found to be less in probiotic groups. We thought that following mechanical obstruction of rats for seven days would result in high mortality. In addition, since we tried to mimic the patient model whose mechanical obstruction was treated with surgery, the samples were taken in the early period. Therefore, differences between the groups may be restricted. Also, we think that the probiotic narrows the gap between cells with edema and thus inhibits bacterial transfer. Cardiopulmonary bypass causes intestinal mucosa damage and bacterial translocation. Ying-Jie Sun et al.[28] gave probiotic mixture to a group of rats where they applied cardiopulmonary bypass. Bacterial translocation to the liver and mesentery was more common in the probiotic group. In our study, BT to liver was lower in P (+)24 group than P (-)24 group, at P (+)48, less than P (-)48. When evaluating mucosal damage, in Chiu scoring,[29] the vascular congestion parameter corresponds to the edema parameter in the scoring we used in our study. In Lutgendorff et al.’s[30] study evaluating intestinal mucosal injury in rats, which produced pancreatitis using glycodeoxycholic acid, gave a group a mixture of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, Lactococcus lactis, Bifidobacterium bifidum and Bifidobacterium lactis, Chiu scoring and the probiotic group, they found less mucosal damage than the group not given. In the probiotic group, an increase and enlargement of the epithelium corresponding to edema was detected, but the structure of the epithelium was intact. Our study showed a significant correlation and edema that was significantly higher in the probiotic group. However, no difference was found in other parameters. Lutgendorff et al. observed a significant difference in tissue GSH values in the probiotic group in the same study. In our study, there was no significant difference between the groups concerning GSH values obtained from tissue and erythrocyte.

Conclusion In this study, we found that probiotics did not reduce the occlusion-induced mucosal damage in the first 48 hours. We Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

have shown a reduction in bacterial translocation. We even showed increased mucosal edema. We think that probiotics may have obstacle on BT, so this may have a decreasing effect on the morbidity and mortality caused by BT. In addition, in our study, the findings suggest that probiotics support antioxidant defense. As a result, it is possible to obtain positive results with the widespread use of probiotics in surgery. However, our study is a preliminary, experimental study. For their effects on humans, more detailed clinical studies are needed. Ethics Committee Approval: Adnan Menderes University Animal Experiments Local Ethics Committee granted approval for this study (date: 27.04.2015, number: 64583101/2015/37). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.E.; Design: A.E.; Supervision: M.H.Ç., M.Y.; Resource: A.D.U., B.A.P.; Materials: A.D.U., D.H.L.; Data: Ç.Y.; Analysis: S.S., İ.M.; Literature search: A.E., M.Y., Ç.Y.; Writing: A.E.; Critical revision: M.H.Ç. Conflict of Interest: The authors declare that have no conflict of interest. Financial Disclosure: The authors declared that this study has received financial support by Adnan Menderes University Scientific Research projects.

REFERENCES 1. Welch JP. General consideration and mortality in bowel obstruction. In: Welch JP, editor. Bowel obstruction: differential diagnosis and clinical management. Philadelphia: Saunders;1990.p.59–95. 2. van der Waaij D, Berghuis-de Vries JM, Lekkerkerk Lekkerkerk-v. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J Hyg (Lond) 1971;69:405−11. 3. Guarner C, Runyon BA, Young S, Heck M, Sheikh MY. Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites. J Hepatol 1997;26:1372−8. 4. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell 2012;148:1258−70. 5. Gerritsen J, Smidt H, Rijkers GT, de Vos WM. Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr 2011;6:209−40. 6. Thomas DW, Greer FR; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Gastroenterology, Hepatology, and Nutrition. Probiotics and prebiotics in pediatrics. Pediatrics 2010;126:1217−31. 7. Chmielewska A, Szajewska H. Systematic review of randomised controlled trials: probiotics for functional constipation. World J Gastroenterol 2010;16:69−75. 8. Deshpande G, Rao S, Patole S. Progress in the field probiotics: year 2011. Curr Opin Gastroenterol 2011;27:13−8. 9. Quirino IE, Correia MI, Cardoso VN. The impact of arginine on bacterial translocation in an intestinal obstruction model in rats. Clin Nutr 2007;26:335−40. 10. Millar AD, Rampton DS, Chander CL, Claxson AW, Blades S, Coumbe A, et al. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut 1996;39:407−15. 11. Aebi H. Catalase. In: Bergmeyer HU, editor. Methods of Enzymatic Analysis. Weinheim, NewYork: Verlag Chemie & Academic Press In-

841

Edizsoy et al. Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic c;1974.p.673−80. 12. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351−8. 13. Konukoglu D, Iynem H, Ziylan E. Antioxidant status in experimental peritonitis: effects of alpha tocopherol and taurolin. Pharmacol Res 1999;39:247−51. 14. Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 1969;27:502−22. 15. Pleban PA, Munyani A, Beachum J. Determination of selenium concentration and glutathione peroxidase activity in plasma and erythrocytes. Clin Chem 1982;28:311−6. 16. Kakkar R, Mantha SV, Radhi J, Prasad K, Kalra J. Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. Clin Sci (Lond) 1998;94:623−32. 17. Racker E. Glutathione reductase (liver and yeast) In: Colowick SP, Kaplan NO, editors. Methods in Enzymology. Vol. 2. New York, NY, USA: Academic Press; 1955.p.722–9. 18. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497−500. 19. Navarro-Gonzálvez JA, García-Benayas C, Arenas J. Semiautomated measurement of nitrate in biological fluids. Clin Chem 1998;44:679−81. 20. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, et al. Measurement of protein using bicinchoninic acid. Anal Biochem 1985;150:76−85. 21. Lu RH, Chang TM, Yen MH, Tsai LM. Involvement of Superoxide Anion in the Pathogenesis of Simple Mechanical Intestinal Obstructi Involvement of superoxide anion in the pathogenesis of simple mechanical intestinal obstruction. J Surg Research 2003;115:184–90. 22. Demirer S, Aydintug S, Aslim B, Kepenekci I, Sengül N, Evirgen O, et al.

Effects of probiotics on radiation-induced intestinal injury in rats. Nutrition 2006;22:179−86. 23. El-Awady SI, El-Nagar M, El-Dakar M, Ragab M, Elnady G. Bacterial translocation in an experimental intestinal obstruction model C-reactiveprotein reliability?. Acta Cirúrgica Brasileira 2009;24:98−106. 24. Aldemir M, Kökoğlu OF, Geyik MF, Büyükbayram H. Effects of octreotide acetate and Saccharomyces boulardii on bacterial translocation in an experimental intestinal loop obstruction model of rats. Tohoku J Exp Med 2002;198:1−9. 25. Generoso SV, Viana M, Santos R, Martins FS, Machado JA, Arantes RM, et al. Saccharomyces cerevisiae strain UFMG 905 protects against bacterial translocation, preserves gut barrier integrity and stimulates the immune system in a murine intestinal obstruction model. Arch Microbiol 2010;192:477−84. 26. Antequera R, Bretaña A, Cirac A, Brito A, Romera MA, Zapata R. Disruption of the intestinal barrier and bacterial translocation in an experimental model of intestinal obstruction. Acta Cientifica Venezola 2000;51:18−26. 27. Mañé J, Lorén V, Pedrosa E, Ojanguren I, Xaus J, Cabré E, et al. Lactobacillus fermentum CECT 5716 prevents and reverts intestinal damage on TNBS-induced colitis in mice. Inflamm Bowel Dis 2009;15:1155−63. 28. Sun YJ, Cao HJ, Song DD, Diao YG, Zhou J, Zhang TZ. Probiotics can alleviate cardiopulmonary bypass-induced intestinal mucosa damage in rats. Dig Dis Sci 2013;58:1528−36. 29. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970;101:478−83. 30. Lutgendorff F, Nijmeijer RM, Sandström PA, Trulsson LM, Magnusson KE, Timmerman HM, et al. Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis. PLoS One 2009;4:e4512.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Geçici mekanik obstrüksiyona maruz kalmış, probiyotik ile beslenen sıçanlarda bağırsak mukozası Dr. Akay Edizsoy,1 Dr. Eyüp Yılmaz,2 Dr. Mehmet Hakan Çevikel,2 Dr. Çiğdem Yenisey,3 Dr. Serhan Sakarya,4 İbrahim Meteoğlu5 Mersin Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Cerrahi Onkoloji, Mersin Adnan Menderes Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Aydın 3 Adnan Menderes Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, Aydın 4 Adnan Menderes Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları Anabilim Dalı, Aydın 5 Adnan Menderes Üniversitesi Tıp Fakültesi, Pataloji Anabilim Dalı, Aydın 1 2

AMAÇ: Mekanik obstrüksiyon nedeniyle ameliyat edilen hastalarda mukozal hasarı ve buna bağlı etkileri önlemek için sıçanlarda bir model oluşturuldu. Bazı gruplara yemleri ile probiyotik verilerek, bazıları ise standart yemlerle beslendi. Bağırsak mukozasının zarar görmesi ve buna bağlı olan etkilerin gruplar arasında farklılık ortaya çıkarması beklendi. GEREÇ VE YÖNTEM: Kırk sekiz dişi wistar-albino tipi sıçan rastgele beş gruba ayrıldı. İlk operasyonda, kontrol grubu dışındaki sıçanların bağırsakları terminal ileum düzeyinde ipek ile bağlandı. İki grup 24, diğer iki grup 48 saat sonra tekrar ameliyat edildi ve terminal ileumdaki obtrüksiyonları kaldırıldı. Bu süre zarfında, 24 ve 48 saat obstrükte kalan gruplardan her birine probiyotik verildi. Yirmi dört saat sonra, kontrol grubu ve diğer gruplar örnekleme için üçüncü kez ameliyat edildi. Terminal ileum, karaciğer, dalak, MLN (mezenterik lenf nodu) ve kan örnekleri alındı. BULGULAR: Kırk sekiz saat boyunca obstrükte kalan ve probiyotiklerle beslenen araştırma grubunda mukozal hücre kaybı ve mukozal ödemde belirgin olarak artış gözlendi. Bakteriyel translokasyon, probiyotik verilmeyen gruplarda daha yaygın bulundu. Doku GR (Glutatyon redüktaz) ve eritrosit CAT (katalaz), 24 saat boyunca tıkalı ve probiyotik verilen grupta daha düşüktü. TARTIŞMA: Probiyotiklerle beslenen gruplardaki yüksek mukozal ödem oranları hasar olarak görülebilir, ancak probiyotiklerin mukozal bariyer etkisi ile uyumlu olduğunu düşünüyoruz. Böylece probiyotiklerle beslenen gruplarda, bakteriyel translokasyonun daha az görülmesi ve bazı antioksidan enzimlerin daha düşük bulunması mümkündür. Probiyotiklerin cerrahi hastalarda yararlarını belirlemek için ileri çalışmalara ihtiyaç vardır. Anahtar sözcükler: Antioksidan enzim; bakteriyel translokasyon; mukozal hasar; obstrüksiyon; probiyotik. Ulus Travma Acil Cerrahi Derg 2020;26(6):833-842

842

doi: 10.14744/tjtes.2020.30269

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

EXPERIMENTAL STUDY

The protective role of probiotics in sepsis-induced rats Mustafa Yılmaz, M.D.,1

Ali Onur Erdem, M.D.2

Department of Biochemistry, Adnan Menderes University Faculty of Medicine, Aydın-Turkey

Department of Pediatric Surgery, Adnan Menderes University Faculty of Medicine, Aydın-Turkey

ABSTRACT BACKGROUND: Probiotic ingestion is associated with an increase in intestinal flora of useful bacteria, which contributes to the known protective effects it has on the intestinal barrier and thereby reducing infection. The present study aims to investigate the protective effect of Lactobacillus rhamnosus gg (LGG) as an important probiotic with gastrointestinal barrier strengthening effect in sepsis. METHODS: Our study was conducted in the Animal Experiments Laboratory after obtaining ethicalapproval to conduct this study. Twenty-four rats were randomly divided into threegroups and group 1 (control group n=8), group 2 (sepsis group, n=8), group 3 (sepsis + probiotic group, n=8) were planned as double-blind. LGG was used as a probiotic. For the sepsis model, E. coli (0111: B4) was injected intraperitoneally, and the rats were sacrificed 48 hours after treatment. Blood samples were collected from all animals before sacrification and sent to the biochemistry laboratory to evaluate oxidant and antioxidant parameters. RESULTS: CRP values of Group 1 were significantly lower than Group 2, and CRP values of Group 3 were significantly lower. While total thiol levels of Group 2 were significantly lower than Group 1, total thiol levels of Group 3 were significantly higher than Group 2. There was no statistically significant difference between the groups for eNOS, GPX, PON1 and MDA levels. CONCLUSION: Prophylactic use of probiotics, such as LGG to reduce bacterial translocation and strengthen the immune system, is an inexpensive and effective method of treatment, and we recommend the repetition of studies supported by prospective clinical trials. Keywords: eNOS; MDA; probiotic; sepsis.

INTRODUCTION Sepsis is a systemic inflammatory response to infection, often not compatible with age, affecting approximately 31.5 million patients worldwide.[1,2] Sepsisis thought to account for about 17% of hospital mortality.[3] Recently, a multinational intensive care unit (ICU) study, which involvedmore than 14,000 patients in more than 1200 ICUs, found that 51% of patients were infected, and 71% were on antibiotics in the survey. In this study, antibiotics used to treat infections ledto loss of gastrointestinal (GI) microbiota and potentially to the overgrowth of pathogens.The disruption of the intestinal barrier with flora wasthe main factor in the development of sepsis.[4] In recent years, randomized, double-blind studies have shown that probiotics administered to patients reduce infection rates.[5,6] The degradation of the intestinal barrier and in-

creased permeability in sepsis is considered one of the most important factors that worsen the situation and probiotics are believed to be protective.[7] Lactobacillus rhamnosus GG (LGG) is one of the most studied probiotics on this subject.[8] Investigating the protective effect of LGG, which is an important probiotic with gastrointestinal barrier strengthening effect on sepsis in prophylactic use, was this study’s aim. For this, we have shown that sepsis-induced C reactive protein (CRP) as an inflammatory indicator, Malondialdehyde (MDA )and endothelial nitric oxide synthase (eNOS) as a marker of oxidation, and we measured the total thiol level of antioxidant molecules, glutathione peroxidase (GPx) and PON1 activity from the 3 Paraoxonases (PON) gene family to evaluate the efficacy of probiotics.

Cite this article as: Yılmaz M, Erdem AO. The protective role of probiotics in sepsis-induced rats. Ulus Travma Acil Cerrahi Derg 2020;26:843-846. Address for correspondence: Ali Onur Erdem, M.D. Adnan Menderes Üniversitesi Tıp Fakültesi Hastanesi, 4 Kat, Merkez Efeler, 09100 Aydın, Turkey Tel: +90 256 - 444 12 56 E-mail: aoerdem@adu.edu.tr Ulus Travma Acil Cerrahi Derg 2020;26(6):843-846 DOI: 10.14744/tjtes.2020.70440 Submitted: 10.07.2019 Accepted: 25.09.2020 Online: 21.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

843

Yılmaz et al. The protective role of probiotics in sepsis-induced rats

MATERIALS AND METHODS After obtaining the ethical approval from Adnan Menderes University Animal Experiments Ethics Committee, our study was conducted in the animal experiments laboratory. Twenty-four young, healthy male Wistar-Albino rats weighing between 250–300 grams were used in thisstudy. The rats were kept in wire cages, 12 hours of light and 12 hours of dark circadian rhythm before the experiment and their temperature was kept at 20–25°C, and the rats were randomized inthreegroups. Group1. (Control group, n=8): Rats were given standard feed and water for 10 days. At the end of the procedure, blood was taken for biochemical examination. Group 2 (Sepsis group, n=8): Rats were fed with standard feed and water for 10 days. Experimental sepsis with E. coli was induced and the rats were kept for twodays, and at the end of twodays, blood was taken for biochemical examination, and rats were sacrificed. Group 3 (Sepsis + Probiotic group, n=8): Standard feed and water were given to rats for 10 days with LGG orogastric tube at a dose of 1x10-7 CFU/day. Experimental sepsis with E. coli was then induced and rats were kept for twodays, and at the end of twodays, blood was taken for biochemical examination, and rats were sacrificed. Blood samples were centrifuged in biochemical tubes and eNOS, CRP, GPX, total thiol, MDA, PON1 tests were studied in each group and compared statistically.

Sepsis Model Lipopolysaccharide derived from E. coli 0111: B4 serotype was injected intraperitoneally at a dose of 15mg/kg for 48 hours.

RESULTS When the groups’ CRP values were examined, the average value of Group 1 was 34.10, the average value of Group 2 was 70.40, and the average value of Group 3 was 39.90. While the Group 1’s value was considerably lower than Group 2’s value, Group 3’s CRP values were considerably lower than Group 2’s CRP values (p=0.00), Gpx values were 61.95 for Group 1, 63.27 for Group 2, and 78.77 (pg/ml) for Group 3. No statistically significant difference was found between the groups (Fig. 1). Althoughthe mean values of eNOS were 55.70, 59.40 and 53.60 for all threegroups, no statistically significant difference was found between them. Malondialdehyde (MDA) values were 15.60 in Group 1 and 28.50 and 23.82 in Group 2 and 3, respectively (p=0.44). Total thiol values were 786.58 in Group 1, 589.30 in Group 2 and 870.96 in Group 3. While the Group 2’s values decreased significantly compared to Group 1, Group 3’s values increased considerably com844

pared to Group 2 (p=0.037) (Fig. 2). PON1 values were 0.29, 0.39, and 0.60 in all threegroups, but there was no statistically considerable difference was among the groups (Fig. 3).

DISCUSSION According to 2016 data of the 3rd International Sepsis consensus, sepsis causing multiple organ failure continues to be 80

Group 1 (Control) Group 2 (Sepsis) Group 3 (Sepsis+L.Rh) *p<0.05

ENOS (µIU/mL)

CRP (ng/mL)

GPX (pg/mL)

MDA (umol/L)

Figure 1. eNOS, CRP, GPX, MDA changes in groups. *P<0.05. 1.200

Thiol (µmol/L) *p<0.05

1.000 800 600 400 200 0

Group 1 (Control)

Group 2 (Sepsis) Group 3 (Sepsis+L.Rh)

Figure 2. Total thiol (SH) µmol/l changes in groups. *P<0.05 1.00

Paraoxa (ng/mL)

.80

.60

.40

.20

.00

Group 1 (Control)

Group 2 (Sepsis) Group 3 (Sepsis+L.Rh)

Figure 3. Paraoxa (ng/mL) changes in groups. *P>0.05.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Yılmaz et al. The protective role of probiotics in sepsis-induced rats

a severecause of mortality in patients who still have an infection in hospitals. Giventhe difficulties and complications of sepsis treatment, it is clear that preventive measures should be taken for patients at risk of sepsis. Strengthening the intestinal flora with probiotic support of the patients in the risk group and may reduce sepsis occurrence and possible complications. Popular studies are currently being conducted with many agents on sepsis, one of which is on probiotics that ensure the integrity of the intestinal barrier and strengthen the host immune mechanism.[9,10] In the study conducted by Panpetch et al.,[11] it is reported that LGG had a positive effect on sepsis, especially by reducing bacterial translocation. Mailänder-Sánchez et al.[12] reported that LGG reduces nosocomial candida infections and thus sepsis, while Kane et al.[13] reported that bacterial permeability and necrotizing enterocolitis risk in neonatal infants.[1,12] In our study on this probiotic, which has an important effect, we compared its effectiveness using various markers and found that it provides significant protection between the probiotic given before sepsis and the sepsis group. We think that this protection obtained in these rats under probiotic prophylaxis may be due to the strengthening effects of the intestinal barrier in parallel with other studies. The use of prophylactic antibiotics to prevent infection in many pre-operative or intensive care patients is still widespread.[4] However, with this method, intestinal flora of many patients who already have nutritional problems will be further deteriorated, and barrier function will be weakened. This will increase the patient’s progression to sepsis ata predictable rate. However, initiation of probiotic supplementation in patients in the risk group whose ICU or oral intake is impaired will strengthen intestinal flora and intestinal barrier function and at least reduce the course of sepsis.In another study of Ávila et al.,[14] it was shown that LGG administered before sepsis formation plays a protective role in rats. In the same study, it was concluded that early initiation of LGG, administeredbetween 7 and 15 days before sepsis formation, has more positive results. In our experimental study, we demonstrated that prophylactic use of LGG, parallel to findings of Ávila’s study, mightbe protective against sepsis. In our study, we demonstrated that prophylactic use of LGG mightbe protective due to sepsis. CRP is a rising protein in stress, chronic inflammation and sepsis. In the sepsis group, CRP significantly increased, and in the prophylactic group, there was a decrease in CRP value.[15] In the study conducted by Rabha et al.,[16] they induced experimental sepsis in rats and treated them with an agent called Kaempferol. MDA and eNOS were high in sepsis groups and low in treatment groups and reported that the agent was effective in treatment. In our study, these markers, which wereoxidative stress markers, were higher in the sepsis group and low in the prophylactic probiotic group. This finding suggeststhat the protective effect of LGG in sepsis provides the Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

level of protection that can be achieved with treatment in some studies. Although PON1 activity was found to contribute to the antioxidant system by reducing the lipidperoxide content of macrophages and increasing the level of glutathione,[17] we did not find such a relationship in our study. GPx is considered to be an indirect marker of tissue antioxidant capacity.[18] GPX values are expected to be lower in sepsis-generated groups. In our study, GPx levels were higher in Group 3. This result may suggest that there is an increase in the antioxidant capacity of the tissue with the given LGG and that the tissue is protected against oxidant stress markers. It is said that probiotics have antioxidant effects, and can therefore, be used to treat many inflammatory diseases.[19–21] Total thiol is an important antioxidant marker of sulfhydryl group.[22] In a retrospective pilot study conducted by Molina et al.,[23] Thiol levels were higher in the control group compared to the septic group. In our study, the other antioxidative stress markers of control and prophylactic groups were higher compared to the sepsis group. This shows that the protective effects of LGG in sepsis. As a result, sepsis still appears to be a public health problem with high mortality in intensive care units and hospitals. Treatment is both difficult and costly. Prophylactic use of probiotics, such as LGG, is an effective and cost-effective treatment modality.We believe that these studies should be repeated and supported by prospective clinical studies. Ethics Committee Approval: Adnan Menderes University Animal Experiments Local Ethics Committee granted approval for this study (date: 20.02.2018, number: 64583101/2018/032). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.Y., A.O.E.; Design: M.Y., A.O.E.; Supervision: A.O.E.; Data: A.O.E.; Analysis: M.Y.; Literature search: M.Y.; Writing: M.Y., A.O.E.; Critical revision: M.Y., A.O.E. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Aravanis CV, Kapelouzou A, Vagios S, Tsilimigras DI, Katsimpoulas M, Moris D, et al. Toll-Like Receptors -2, -3, -4 and -7 Expression Patterns in the Liver of a CLP-Induced Sepsis Mouse Model. J Invest Surg 2020;33:109–17. 2. Gad SC. Acute and chronic systemic chromium toxicity. Sci Total Environ 1989;86:149–57. 3. Vincent JL, Opal SM, Marshall JC, Tracey KJ. Sepsis definitions: time for change. Lancet 2013;381:774–5. 4. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al; EPIC II Group of Investigators. International study of the prevalence and

845

Yılmaz et al. The protective role of probiotics in sepsis-induced rats outcomes of infection in intensive care units. JAMA 2009;302:2323–9. 5. Barraud D, Blard C, Hein F, Marçon O, Cravoisy A, Nace L, et al. Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial. Intensive Care Med 2010;36:1540–7. 6. Jain PK, McNaught CE, Anderson AD, MacFie J, Mitchell CJ. Influence of synbiotic containing Lactobacillus acidophilus La5, Bifidobacterium lactis Bb 12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose on gut barrier function and sepsis in critically ill patients: a randomised controlled trial. Clin Nutr 2004;23:467–75. 7. Erel VK, Yılmaz EM. Prospective effect of B. clasuii on sepsis. J Ann Eu Med 2018;6:20–3. 8. Bauserman M, Michail S. The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial. J Pediatr 2005;147:197–201. 9. Matsumoto T, Ishikawa H, Tateda K, Yaeshima T, Ishibashi N, Yamaguchi K. Oral administration of Bifidobacterium longum prevents gut-derived Pseudomonas aeruginosa sepsis in mice. J Appl Microbiol 2008;104:672–80. 10. Ramos MFP, Monteiro de Barros ADCM, Razvickas CV, Borges FT, Schor N. Xanthine oxidase inhibitors and sepsis. Int J Immunopathol Pharmacol 2018;32:2058738418772210. 11. Panpetch W, Chancharoenthana W, Bootdee K, Nilgate S, Finkelman M, Tumwasorn S, et al. Lactobacillus rhamnosus L34 Attenuates Gut Translocation-Induced Bacterial Sepsis in Murine Models of Leaky Gut. Infect Immun 2017;86:e00700–17. 12. Mailänder-Sánchez D, Braunsdorf C, Grumaz C, Müller C, Lorenz S, Stevens P, et al. Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion. PLoS One 2017;12:e0184438. 13. Kane AF, Bhatia AD, Denning PW, Shane AL, Patel RM. Routine Supplementation of Lactobacillus rhamnosus GG and Risk of Necrotizing Enterocolitis in Very Low Birth Weight Infants. J Pediatr 2018;195:73–9.e2.

14. Ávila PRM, Michels M, Vuolo F, Bilésimo R, Burger H, Milioli MVM, et al. Protective effects of fecal microbiota transplantation in sepsis are independent of the modulation of the intestinal flora. Nutrition 2020;73:110727. 15. Nazaretyan VV, Lukach VN, Kulikov AV. Predictors of Unfavorable Outcome in Patients with Abdominal Sepsis.. Anesteziol Reanimatol 2017;61:209–15. 16. Rabha DJ, Singh TU, Rungsung S, Kumar T, Parida S, Lingaraju MC, et al. Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice. Exp Lung Res 2018;44:63–78. 17. Tanoglu A, Yamanel L, Inal V, Ocal R, Comert B, Bilgi C. Appreciation of trimetazidine treatment in experimental sepsis rat model. Bratisl Lek Listy 2015;116:124–7. 18. Fuhrman B, Volkova N, Aviram M. Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase. Atherosclerosis 2002;161:307–16. 19. Amdekar S, Roy P, Singh V, Kumar A, Singh R, Sharma P. Anti-inflammatory activity of lactobacillus on carrageenan-induced paw edema in male wistar rats. Int J Inflam 2012;2012:752015. 20. Rijkers GT, de Vos WM, Brummer RJ, Morelli L, Corthier G, Marteau P. Health benefits and health claims of probiotics: bridging science and marketing. Br J Nutr 2011;106:1291–6. 21. Singhi SC, Kumar S. Probiotics in critically ill children. F1000Res 2016;5:F1000 Faculty Rev-407. 22. Unal S, Ulubas Isik D, Bas AY, Erol S, Arifoglu İ, Alisik M, et al. Evaluation of dynamic thiol-disulfide homeostasis in very low-birth-weighted preterms. J Matern Fetal Neonatal Med 2019;32:1111–6. 23. Molina V, von Dessauer B, Rodrigo R, Carvajal C. Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study. Redox Rep 2017;22:330–7.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sepsis oluşturulan sıçanlarda probiyotiklerin koruyucu rolü Dr. Mustafa Yılmaz,1 Dr. Ali Onur Erdem2 1 2

Adnan Menderes Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Aydın Adnan Menderes Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Aydın

AMAÇ: Oral alınan probiyotikler ile bağırsaklarda faydalı bakterilerin artırıldığı ve bu sayede bağırsakların enfeksiyonlar için koruyucu bariyer gücünün arttığı bilinmektedir. Bağırsak bariyer gücünün azalması ise oluşacak sepsiste tablonun kötüleşmesinde en önemli parametrelerden birisi olduğuna inanılmaktadır. Bağırsak bariyer gücünün artırılmasında birçok probiyotiğin etkili olduğu gösterilmiştir. Lactobacillus rhamnosus GG (LGG) bu konuda çalışılmış probiyotiklerden biridir. Bu çalışmanın amacı sepsis üzerine gastrointestinal bariyer güçlendirici etki için önemli bir probiyotik olan LGG’nin koruyucu etkisini araştırmaktır. GEREÇ VE YÖNTEM: Çalışmamız Adnan Menderes Üniversitesi Hayvan Deneyleri Etik Kurulu onayı alındıktan sonra hayvan deneyleri laboratuvarında yapıldı. Çalışmada ağırlıkları 250–300 gram arasında değişen 24 adet genç sağlıklı erkek Wistar-Albino sıçan kullanıldı. Sıçanlar, deney öncesi tel kafeslerde, 12 saat aydınlık 12 saat karanlık sirkadiyen ritimde ve sıcaklığı 20–25 °C’de tutuldu. Yirmi dört sıçan rastgele olarak üç gruba ayrıldı ve Grup 1 (kontrol grubu, n=8), Grup 2 (sepsis grubu, n=8), Grup 3 (sepsis + probiyotik grubu, n=8) olarak çift kör şeklinde planlandı. Probiyotik olarak LGG 1x10–7 CFU/gün kullanıldı. Sepsis modeli için E. coli’nin serotiplerinden (0111: B4) ekstrakte edilen lipopolisakarit, 15 mg/kg’lık bir dozda intraperitoneal olarak enjekte edildi ve sıçanlar işemden 48 saat sonra sakrifiye edildi. Sakrifikasyon öncesi tüm hayvanlardan kan örnekleri alındı ve bu örnekler biyokimya laboratuvarına oksidan ve antioksidan parametreler değerlendirilmek üzere gönderildi. BULGULAR: Grup 1’in CRP değeri Grup 2’den, Grup 3’ün de CRP değerleri Grup 2’den anlamlı olarak düşük saptandı, Grup 2’nin total tiyol seviyeleri Grup 1’e göre anlamlı derecede düşük iken, Grup 3’ün total tiyol seviyeleri Grup 2’den anlamlı derecede yüksek saptandı. eNOS, GPX, PON1 ve MDA düzeyleri için ise gruplar arasında istatistiksel olarak anlamlı bir fark yoktu. TARTIŞMA: Bakteriyel translokasyonu azaltmak ve bağışıklık sistemini güçlendirmek için LGG gibi probiyotiklerin proflaktik olarak kullanımı, tedavi için ucuz ve etkili bir yöntemdir ve bu çalışmaların tekrarlanarak ileriye yönelik klinik çalışmalarla desteklenmesini öneriyoruz. Anahtar sözcükler: eNOS; MDA; probiyotik; sepsis. Ulus Travma Acil Cerrahi Derg 2020;26(6):843-846

846

doi: 10.14744/tjtes.2020.70440

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

EXPERIMENTAL STUDY

Ameliorating the effects of Adalimumab on rabbits with experimental cerebral vasospasm after subarachnoid hemorrhage Gökhan Toğuşlu, M.D.,1 Mehmet Fatih Erdi, M.D.,2 Densel Araç, M.D.,2 Fatih Keskin, M.D.,2 İbrahim Kılınç, M.D.,3 Gökhan Cüce, M.D.4 1

Department of Neurosurgery, Kadirli State Hospital, Osmaniye-Turkey

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

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

Department of Histology and Embryology, Necmettin Erbakan University Meram Faculty of Medicine, Konya-Turkey

ABSTRACT BACKGROUND: Adalimumab (ADA), which is a new-generation recombinant human monoclonal antibody for tumor necrosis factor α (TNFα), has strong anti-inflammatory effects. The role of enhanced inflammation is well established for the development and progression of cerebral vasospasm. Investigated in the present study is the probable ameliorating and neuroprotective effects of ADA in rabbits using a cerebral vasospasm model with biochemical and histopathological methods. METHODS: Thirty male New-Zealand white rabbits were randomly divided into control, subarachnoid hemorrhage (SAH) only and SAH plus ADA treatment groups. SAH was established as a single cisterna magna autologous arterial blood injection. ADA treatment was started just after intracisternal blood injection and continued for 72 hours once a day. The animals were sacrificed 72 hours after the induction of SAH, serum and brainstem tissue obtained for investigations. RESULTS: Brainstem tissue and plasma levels of tumor necrosis factor-alpha and Interleukin-1β, brainstem tissue Matrix metalloproteinase-9 levels increased after SAH and partly decreased after treatment. Plasma levels of brain-derived neurotrophic factor decreased after SAH and partly restored after treatment. ADA treatment significantly increased the mean cross-sectional area of the vasospastic basilar arteries, reduced the basilar artery wall thickness and also ameliorates enhanced endothelial apoptosis. CONCLUSION: Findings obtained in this study suggest that ADA is an effective neuroprotective agent for ameliorating cerebral vasospasm in experimental rabbit vasospasm. Keywords: Adalimumab; cerebral vasospasm; cytokine; inflammation; neuroprotection; rabbit; subarachnoid hemorrhage.

INTRODUCTION Cerebral vasospasm is an important complication of subarachnoid hemorhage (SAH), which leads to enhanced mortality and morbidity. Despite intensive studies, its multifactorial pathogenesis is not elucidated yet.[1] Enhanced inflammation has been postulated as an important cause of vasospasm in both experimental[2] and clinical[3] studies. Increased levels of adhesion molecules have been found in both cerebrospinal

fluid (CSF) and serum of SAH patients, which may lead to the accumulation of leukocytes in inflamed tissue.[4] Enhanced cytokines[3] and activated complement system play important roles in[4] initiation of the multifaceted cascade of vasospasm after SAH. Tumor necrosis factor-alpha (TNFα) is an important proinflammatory cytokine that regulates systemic inflammation. Adalimumab (ADA) is a recombinant human IgG1 monoclonal antibody for TNFα, which binds TNFα by antigen-antibody interaction and inhibits its binding to its re-

Cite this article as: Toğuşlu G, Erdi MF, Araç D, Keskin F, Kılınç İ, Cüce G. Ameliorating the effects of Adalimumab on rabbits with experimental cerebral vasospasm after subarachnoid hemorrhage. Ulus Travma Acil Cerrahi Derg 2020;26:847-852. Address for correspondence: Densel Araç, M.D. Necmmetin Erbakan Üniversitesi Meram Tıp Fakültesi, Nöroşirurji Anabilim Dalı, Konya, Turkey Tel: +90 332 - 223 61 50 E-mail: denselarac@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):847-852 DOI: 10.14744/tjtes.2019.52504 Submitted: 03.09.2019 Accepted: 31.12.2019 Online: 21.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

847

Toğuşlu et al. Ameliorating the effects of ADA on rabbits with experimental cerebral vasospasm after SAH

ceptor.[5] In this study, we aimed to investigate the effects of ADA on experimentally induced cerebral vasospasm by its strong anti-inflammatory properties.

dosage and treatment regimen was decided according to the literature.[6] The animals tolerated this dosage well without any important side effects.

MATERIALS AND METHODS

The animals were sacrificed under general anesthesia 72 hours after the induction of SAH. Before sacrification, 2cc fresh arterial blood was obtained from the ear artery of each rabbit. All rabbits were transcardiac perfused, as described. The thorax was opened and a cannula was placed in the aorta using the left ventricle. The right atrial appendage was opened, and the descending thoracic aorta clamped. The vascular system was perfused with 300 ml of physiological saline under a pressure of 120 cm H2O.

The experimental protocol was approved by the local Animal Ethics Committee (2016-042). All animals breathed spontaneously throughout the procedures. Arterial blood samples were taken from each animal from the catheterized ear arteries for blood gas analysis during the procedures. Heart rate and systemic blood pressure were measured with the use of an ear artery catheter. Core body temperature was monitored rectally and maintained at 37°±0.5°C with a heater. Mean physiological parameter values were not statistically significant between the groups (p>0.05). Cerebral vasospasm was obtained by a single fresh nonheparininized autologous arterial blood injection to the cisterna magna of the rabbit.[1] Briefly, the head of the rabbit was extended in the prone position. With the use of aseptic techniques, a midline nuchal incision was made, the atlanto-occipital membrane was exposed and cisterna magna was punctured by a 25 gauge needle. 1.0 mL/kg of cerebrospinal fluid was withdrawn and an equal volume of blood injected into the cisterna magna within two minutes. Layers closed in anatomical planes after the needle were withdrawn. The animals were then placed in a head-down position for 15 minutes to facilitate blood settling around the basilar artery. After the recovery from anesthesia, and confirmation of vital signs, rabbits were left to their cages.

Groups Thirty male New-Zealand white rabbits weighing 2000–3000 g were assigned randomly into three groups as follows: group 1: control group (n=10), group 2: SAH alone group (n=10), group 3: SAH + ADA treatment group. Group I (control group, n=10) was a sham surgery group in which SAH was not induced. In this group, after induction of anesthesia, the atlanto-occipital membrane was exposed as described above and the cisterna magna was aseptically punctured by a 25-gauge needle, and 1 mL/kg of physiological saline (0.9% NaCl) was slowly injected into the cisterna magna after removal of the same amount of CSF. In group II (SAH only group, n=10), the SAH protocol was used to induce cerebral vasospasm as described above. In group III (SAH + ADA group, n=10), cerebral vasospasm was induced by SAH, as described above, and the rabbits received ADA (Humira, Abbott Laboratories, North Chicago, IL, USA) treatment. ADA 5 mg/kg/day was given intraperitoneally. The treatment was started just after intracisternal blood injection and continued for 72 hours once a day. This 848

After perfusion, the brain and brainstem were removed, and each brainstem cut coronally into two pieces as follows: the anterior part that contains basilar artery histopathological investigations and the dorsal part that contains brainstem tissue for biochemical investigations.

Biochemical Procedures Brainstem tissues (dorsal part) of the rabbits were extracted after decapitation and rinsed with ice-cold PBS (phosphate-buffered saline) containing heparin and blood and clot remnants were removed. Subsequently, tissues were blotted on filter paper and stored in Eppendorf tubes at -80°C until biochemical analysis. Brain tissue samples were weighed and homogenized. Homogenates were centrifuged at +4C° and 10.000 g for 10 minutes. Serum concentrations of the brain-derived neurotrophic factor (BDNF), TNFα, interleukin 1 beta (IL-1β) and brainstem tissue concentrations of the matrix metalloproteinase (MMP9), TNFα and IL-1β were measured using the iMark™ Microplate Absorbance Reader, (Bio-rad Laboratories, CA, USA) using ELISA (enzyme-linked immunosorbent assay) analysis with rabbit BDNF, TNFα and IL-1β kits (Sunred Biological Technology Co., Ltd, Shanghai, China). Tissue protein levels were measured using the Thermo Scientific Pierce™ BCA Protein Assay Kit (Thermo Fisher Scientific, IL, USA).

Histopathological Procedures In total, five artery sections were analysed per animal. The morphometric and immunohistological analyses were carried out in a blind fashion by one pathologist. Morphometric measurements on all five segments of the basilar artery were performed using an image analysis system (BAB image analysing systems, Ankara, Turkey). The luminal area was calculated from the perimeter of the luminal border and the area contained within the boundaries of the internal elastic lamina was neglected. The luminal area for each basilar artery was obtained by averaging these measurements. The mean± standard error of the mean (SEM) value obtained from each artery was used as the final value for a particular vessel. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Toğuşlu et al. Ameliorating the effects of ADA on rabbits with experimental cerebral vasospasm after SAH

For labeling apoptotic cells in samples by modifying DNA fragments utilizing terminal deoxynucleotidyl transferase for detection of apoptotic cells by specific staining the ApopTag® Plus Peroxidase In Situ Apoptosis Detection Kit (CHEMICON® International, Inc.) was used as described in user manual. An apoptotic index was calculated as the number of the immunoreactive nuclei per total number of endothelial cells and the result was expressed as a percentage.

Statistical Analysis The SPSS (version 21.0, IBM SPSS Statistics, IL, USA) program was used to evaluate the findings of this study. The differences among groups were tested using the Kruskal-Wallis test. The Post-Hoc Bonferroni and Mann-Whitney U tests were used for the correction of groups in which diference were significant. A P-value less then 0.05 was accepted as significant (p<0.05).

RESULTS All thirty animals survived to complete this study. The animals in the SAH only group was hypoactive and lethargic. Rabbits in the control group and ADA treated groups were as active as they were before.

Biochemical Results Tissue levels of TNFα, IL-1β and MMP-9 elevated in the group 2 and they partly decreased in the group III. Plasma levels of TNFα and IL-1β also elevated in group II and partly decreased in the group III. In contrast, plasma levels of BDNF were higher in the group I, significantly reduced in group II and partly restored in group III. Findings are summarized in Table 1.

Histopathological Results The mean cross-sectional area of the basilar artery significantly reduced after SAH when compared with group I. ADA treatment statistically significantly increased the mean cross-sectional area of the basilar artery when compared with group II. SAH-induced cerebral vasospasm significantly increased the wall thickness of the basilar artery, and ADA treatment statistically significantly reduced this increment. SAH statistically significantly increased the mean percentage of endothelial apoptotic cells when compared with group I. ADA treatment leads to a statistically significant reduction in the mean percentage of apoptotic endothelial cells when compared with group II. Morphometric and immunohistological results were presented in Table 2 and Figure 1 and Figure 2.

DISCUSSION Cerebral vasospasm is an important complication of SAH, which leads to enhanced mortality and morbidity.[7] Despite extensive clinical and experimental studies, exact treatment of vasospasm is obscure. Multifactorial ethiopathogenesis of the vasospasm include lipid peroxide formation, an instability among endothelium-derived vasoconstrictor and vasodilator substances, nitric oxide toxicity, arachidonic acid metabolites, inflammatory cascades, a deterioration of neuronal mechanisms that regulate vascular tone, endothelial proliferation, and apoptosis.[8] SAH triggers a systemic inflammatory cascade, which increases the level of circulating leukocytes and adhesion molecules, which cause accumulation of immunoreactive cells.[4] Progressing inflammatory response in the subarachnoid space is mediated by the release of various cytokines. Fassbender et

Table 1. Brainstem tissue and plasma levels of the biochemical parameters

Tissue TNFα (pg/mg protein)

Tissue IL-1β (pg/mg protein)

Tissue MMP9 (ng/mg protein)

Plasma BDNF (pg/mL)

Plasma TNFα (pg/mL)

Plasma IL-1β (pg/mL)

Group I 1.16±0.16 1.90±0.16 0.61±0.06 661.60±56.68 18.26±7.36 25.64±1.08 Group II 3.39±1.52 5.71±3.72 1.29±0.20 293.80±29.32 44.86±2.58 55.00±3.92 Group III

1.40±0.14* 2.82±0.37* 0.85±0.09* 435.30±33.27* 23.23±1.29* 50.05±2.21*

*Statistically significantly difference when compared with group II (p<0.05). The presented values were given as the mean±SEM.

Table 2. Morphometric and immunohistological results

Cross-sectional area (μm2)

Wall thickness (μm)

Apoptotic Index (%)

Group I

89202±3609

41.67±1.57

3.3±0.47

Group II

53231±1921

65.42±0.95

36.4±2.07

Group III

67687±1800* 51.07±1.23* 16.9±1.36*

*Statistically significantly difference when compared with group II (p<0.05). The presented values were given as the mean±SEM.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

849

Toğuşlu et al. Ameliorating the effects of ADA on rabbits with experimental cerebral vasospasm after SAH

(a)

(b)

(c)

Figure 1. Representative hematoxylin–eosin (H&E)-stained basiller artery sections. (a) Group I, (a) Group II, (a) Group III (Bar=100 µm).

(a)

(b)

(c)

Figure 2. (a) Representative basiller artery sections stained in the TUNEL assay. (a) Group I, (b) Group II, (c) Group III. The black arrows indicate immunoreactive apoptotic endothelial cells (Bar=50 µm).

al.[3] and Takizawa et al.[9] reported an association between cytokines (powerful mediators and regulators of immune responses) in the CSF of patients with cerebral vasospasm after SAH. Takizawa et al.[9] concluded that regulation of cytokines might become a method to prevent complications following SAH. Bowman et al.[10,11] reported some therapeutic effects of cytokine-mediated treatments in the management of experimental cerebral vasospasm. A few cytokines, including TNFα, IL-1, IL-6, and IL-8, have been found to be upregulated in cerebral vasospasm.[12] Among these cytokines, TNFα takes particular interest in the development and progression of some central nervous diseases, including multiple sclerosis,[13] Alzheimer’s disease[14] and autoimmune encephalomyelitis.[15,16] ADA is a human monoclonal TNFα antibody drug that blocks the effects of TNFα. Adalimumab is used successfully for the treatment of disorders, such as Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis.[5,17] To our knowledge, to date, there is no study in the literature concerning the beneficial effects of ADA on cerebral vasospasm. Inflammatory cytokines, TNFα and IL-1β, have been shown to play a role in the development and progression of cerebral vasospasm and ischemia response after cerebral hemorrhage by accelerating the inflammatory response cascade.[18–20] In addition, TNFα and IL-1β play important roles in the activation of the apoptotic process.[21,22] Previous studies showed that the prevention of apoptosis ameliorates cerebral vasospasm.[8,23] MMP-9 is a collagen-degrading enzyme altering blood-brain 850

barrier. Both have similar deleterious effects on the ischemic brain.[24] Recent clinical evidence verified the involvement of MMP-9 in the pathological process of hemorrhagic stroke and aggravation of the early brain injury and cerebral vasospasm after SAH.[25] TNFα induces MMP-9 expression by some signaling pathways that contribute to enhanced inflammation.[26] Inhibiting TNFα by ADA treatment ameliorates MMP-9 related joint inflammation in psoriasis patients.[27] In the present study, ADA treatment after experimental SAH ameliorates the emerging cerebral vasospasm by decreasing brainstem tissue TNFα, IL-1β, MMP-9 levels and plasma levels of TNFα and IL-1β. BDNF have well-known neurotrophic actions and also maintains other neuroprotective effects, including anti-apoptosis, anti-oxidation, and suppression of autophagy. Various protective mechanisms of BDNF against mitochondrial dysfunction commonly associated with the pathogenesis of many chronic neurodegenerative disorders and the protective signaling pathways revealed by BDNF is under investigation for prevention from the progression of neurodegeneration.[28] In our study, plasma levels of BDNF as a marker of neuroprotection were also restored in the ADA treatment group. Cerebral vasospasm affects all layers of the arterial wall with morphologic changes observed in the adventitia, media and intima. Cellular proliferation of cells in the arterial wall and apoptosis of endothelial cells leading to impairment of endothelium-dependent vasorelaxation promotes exposure of vascular smooth muscle cells to spasmogens and enhances vasospasm.[8] In this study, ADA treatment significantly inUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Toğuşlu et al. Ameliorating the effects of ADA on rabbits with experimental cerebral vasospasm after SAH

creased the mean cross-sectional area of the vasospastic basilar arteries, reduced the basilar artery wall thickness and also ameliorates enhanced endothelial apoptosis.

Conclusion The findings obtained in this study suggest that ADA caused significant changes in cytokine activity, with positive effects on the amelioration of cerebral vasospasm. Beneficial anti-inflammatory, anti-apoptotic, neuroprotective effects of ADA worth further investigation for the implement this treatment option into the clinical practice. Ethics Committee Approval: The Necmettin Erbakan University KONÜDAM Experimental Medicine Application and Research Center Directorate granted approval for this study (date: 29.07.2016, number: 2016-042). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.F.E., G.T.; Design: M.F.E., G.T., D.A., F.K.; Supervision: M.F.E.; Resource: G.T.; Materials: G.T.; Data: G.T., M.F.E., F.K., İ.K., G.C.; Analysis: G.T., M.F.E., F.K., İ.K., G.C.; Literature search: M.F.E., D.A., F.K.; Writing: M.F.E., D.A.; Critical revision: M.F.E., F.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Erdi MF, Guney O, Kiyici A, Esen H. The effects of alpha lipoic acid on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit. Turk Neurosurg 2011;21:527−33. 2. Bavbek M, Polin R, Kwan AL, Arthur AS, Kassell NF, Lee KS. Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Stroke 1998;29:1930−6. 3. Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schütt S, et al. Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 2001;70:534−7. 4. Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T, Ley KF, et al. Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 2003;53:123−35. 5. Tsilimbaris M, Diakonis VF, Naoumidi I, Charisis S, Kritikos I, Chatzithanasis G, et al. Evaluation of potential retinal toxicity of adalimumab (Humira). Graefes Arch Clin Exp Ophthalmol 2009;247:1119−25. 6. Polat E, Dağlıoğlu E, Menekşe G, Dike MS, Özdöl Ç, Türk CÇ, et al. Neuroprotective effects of adalimumab on rats with experimental peripheral nerve injury: An electron microscopic and biochemical study. Ulus Travma Acil Cerrahi Derg 2016;22:134−8. 7. Bramlett HM, Dietrich WD. Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J Cereb Blood Flow Metab 2004;24:133−50. 8. Kolias AG, Sen J, Belli A. Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: putative mechanisms and novel approaches. J Neurosci Res 2009;87:1−11. 9. Takizawa T, Tada T, Kitazawa K, Tanaka Y, Hongo K, Kameko M, et al. Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol Res 2001;23:724−30.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

10. Bowman G, Dixit S, Bonneau RH, Chinchilli VM, Cockroft KM. Neutralizing antibody against interleukin-6 attenuates posthemorrhagic vasospasm in the rat femoral artery model. Neurosurgery 2004;54:719−26. 11. Bowman G, Bonneau RH, Chinchilli VM, Tracey KJ, Cockroft KM. A novel inhibitor of inflammatory cytokine production (CNI-1493) reduces rodent post-hemorrhagic vasospasm. Neurocrit Care 2006;5:222−9. 12. Siasios I, Kapsalaki EZ, Fountas KN. Cerebral vasospasm pharmacological treatment: an update. Neurol Res Int. 2013;2013:571328. 13. Sharief MK, Hentges R. Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991;325:467−72. 14. Decourt B, Lahiri DK, Sabbagh MN. Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease. Curr Alzheimer Res 2017;14:412−25. 15. Rostami Mansoor S, Allameh A, Parsian H. An Apparent Correlation Between Central Nervous System and Kidney’s Erythropoietin and TNF Alpha Expression at Peak Experimental Autoimmune Encephalomyelitis Disease. J Mol Neurosci 2018;65:246−54. 16. Selmaj K, Raine CS, Cross AH. Anti-tumor necrosis factor therapy abrogates autoimmune demyelination. Ann Neurol 1991;30:694−700. 17. Celik H, Karatay M, Erdem Y, Yildirim AE, Sertbas I, Karatay E, et al. The Biochemical, Histopathological and Clinical Comparison of the Neuroprotective Effects of Subcutaneous Adalimumab and Intravenous Methylprednisolone in an Experimental Compressive Spinal Cord Trauma Model. Turk Neurosurg 2016;26:622−31. 18. Silva Y, Leira R, Tejada J, Lainez JM, Castillo J, Dávalos A; Stroke Project, Cerebrovascular Diseases Group of the Spanish Neurological Society. Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage. Stroke 2005;36:86−91. 19. Achrol AS, Pawlikowska L, McCulloch CE, Poon KY, Ha C, Zaroff JG, et al; UCSF BAVM Study Project. Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. Stroke 2006;37:231−4. 20. Yang G, Shao GF. Elevated serum IL-11, TNF α, and VEGF expressions contribute to the pathophysiology of hypertensive intracerebral hemorrhage (HICH). Neurol Sci 2016;37:1253−9. 21. Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 1996;274:78−9. 22. Petrache I, Otterbein LE, Alam J, Wiegand GW, Choi AM. Heme oxygenase-1 inhibits TNF-alpha-induced apoptosis in cultured fibroblasts. Am J Physiol Lung Cell Mol Physiol 2000;278:L312−9. 23. Sen O, Caner H, Aydin MV, Ozen O, Atalay B, Altinors N, et al. The effect of mexiletine on the level of lipid peroxidation and apoptosis of endothelium following experimental subarachnoid hemorrhage. Neurol Res 2006;28:859−63. 24. Singh S, Houng AK, Reed GL. Matrix Metalloproteinase-9 Mediates the Deleterious Effects of α2-Antiplasmin on Blood-Brain Barrier Breakdown and Ischemic Brain Injury in Experimental Stroke. Neuroscience 2018;376:40−7. 25. Dang B, Duan X, Wang Z, He W, Chen G. A Therapeutic Target of Cerebral Hemorrhagic Stroke: Matrix Metalloproteinase- 9. Curr Drug Targets 2017;18:1358−66. 26. Lin CC, Tseng HW, Hsieh HL, Lee CW, Wu CY, Cheng CY, et al. Tumor necrosis factor-alpha induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-kappaB in A549 cells. Toxicol Appl Pharmacol 2008;229:386−98. 27. Buommino E, De Filippis A, Gaudiello F, Balato A, Balato N, Tufano MA, et al. Modification of osteopontin and MMP-9 levels in patients with psoriasis on anti-TNF-α therapy. Arch Dermatol Res 2012;304:481−5. 28. Chen SD, Wu CL, Hwang WC, Yang DI. More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy. Int J Mol Sci 2017;18:545.

851

Toğuşlu et al. Ameliorating the effects of ADA on rabbits with experimental cerebral vasospasm after SAH

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Adalimumab’ın tavşanlarda deneysel subaraknoid kanama sonrası oluşan serebral vazospasm üzerine iyileştirici etkileri Dr. Gökhan Toğuşlu,1 Dr. Mehmet Fatih Erdi,2 Dr. Densel Araç,2 Dr. Fatih Keskin,2 Dr. İbrahim Kılınç,3 Dr. Gökhan Cüce4 Kadirli Devlet Hastanesi, Beyin Cerrahisi Kliniği, Osmaniye Necmmetin Erbakan Üniversitesi Meram Tıp Fakültesi, Nöroşirurji Anabilim Dalı, Konya Necmmetin Erbakan Üniversitesi Meram Tıp Fakültesi, Tıbbi Biokimya Anabilim Dalı, Konya 4 Necmmetin Erbakan Üniversitesi Meram Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Konya 1 2 3

AMAÇ: Tümör nekroz faktörü a (TNFa) için yeni nesil bir rekombinant insan monoklonal antikoru olan adalimumab (ADA), güçlü anti-enflamatuvar etkilere sahiptir. Serebral vazospazmın gelişimi ve ilerlemesi için artmış enflamasyonun rolü detaylı bir şekilde belirlenmiştir. Bu çalışmada, tavşanlarda deneysel olarak oluşturulan serebral vazospazm modelinde ADA’nın biyokimyasal ve histopatolojik yöntemlerle muhtemel hafifletici ve nöroprotektif etkileri araştırıldı. GEREÇ VE YÖNTEM: Otuz adet erkek Yeni Zelanda beyaz tavşanı rastgele kontrol, sadece subaraknoid kanama (SAH) ve SAH artı ADA tedavi gruplarına ayrıldı. SAH, tek sisterna magna otolog arteriyel kan enjeksiyonu ile oluşturuldu. ADA tedavisine intrasisternal kan enjeksiyonundan hemen sonra başlandı ve günde 72 saat devam edildi. Araştırmalar için elde edilen SAH, serum ve beyin sapı dokusunun uyarılmasından 72 saat sonra hayvanlar öldürüldü. SAK oluşumundan 72 saat sonra araştırma için serum ve beyin sapı doku örnekleri alındıktan sonra hayvanlar sakrifiye edildi. BULGULAR: Beyin sapı dokusu ve plazma TNFa ve interlökin-1β, beyin sapı dokusu matriks metaloproteinaz-9 seviyeleri SAH sonrasında arttı ve tedaviden sonra kısmen azaldı. Beyin kaynaklı nörotrofik faktörün plazma seviyeleri SAH sonrasında azaldı ve tedaviden sonra kısmen restore edildi. ADA tedavisi, vazospastik baziler arterlerin orta kesit alanını önemli ölçüde arttırdı, baziler arter duvarı kalınlığını düşürdü ve ayrıca endotelyal apoptozisi düzeltti. TARTIŞMA: Sonuçlar ADA’nın deneysel tavşan vazospazmında, serebral vazospazmı iyileştirmede etkili bir nöroprotektif ajan olduğunu göstermektedir. Anahtar sözcükler: Adalimumab; enflamasyon; nöroproteksiyon; serebral vazospasm; subaraknoid kanama; sitokin; tavşan. Ulus Travma Acil Cerrahi Derg 2020;26(6):847-852

852

doi: 10.14744/tjtes.2019.52504

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

EXPERIMENTAL STUDY

Effects of Algan Hemostatic Agent on bleeding time in a rat tail hemorrhage model Özgün Melike Gedar Totuk, M.D.,1 Şevket Ergun Güzel, M.D.,2 Hüsamettin Ekici, M.D.,3 Ali Kumandaş, M.D.,4 Selda Emre Aydıngöz, M.D.,5 Enis Çağatay Yılmaz, M.D.,6 Taylan Kırdan, M.D.,7 Ahmet Midi, M.D.8 1

Department of Ophthalmology, Bahçeşehir University Faculty of Medicine, İstanbul-Turkey

Department of Orthopedics and Traumatology, T.C. Ministry of Health Adıyaman Kahta State Hospital, Adıyaman-Turkey

Department of Pharmacology and Toxicology, Kırıkkale University Faculty of Veterinary Medicine, Kırıkkale-Turkey

Department of Surgery, Kırıkkale University Faculty of Veterinary Medicine, Kırıkkale-Turkey

Department of Pharmacology, Başkent University Faculty of Medicine, Ankara-Turkey

Bahçeşehir University Faculty of Medicine, 4rd Grade Student, İstanbul-Turkey

Bahçeşehir University Faculty of Medicine, 5th Grade Student, İstanbul-Turkey

Department of Pathology, Bahçeşehir University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Algan Hemostatic Agent (AHA) is a multi-herbal extract containing a standardized amount of Achillea millefolium, Juglans regia, Lycopodium clavatum, Rubus caesius or Rubis fruciosus, Viscum album, and Vitis vinifera, each of which is effective in hemostasis. In this study, we aimed to investigate the effects of AHA on bleeding time in a rat tail hemorrhage model. METHODS: Forty-eight Sprague Dawley rats (5–7 weeks old, 180–210 g) were randomly and equally allocated to six groups as follows: heparin plus saline (heparinized control), heparin plus AHA-soaked sponge, heparin plus liquid form of AHA, saline (non-heparinized control), AHA-soaked sponge and liquid form of AHA. Heparin (640 IU/kg) was administered intraperitoneally three times a day for three days in heparinized groups. For the bleeding model, the tail of rats was transected. According to the study group, either saline- or AHA-soaked sponge or liquid form of AHA was applied over the hemorrhage area. In AHA- or saline-soaked sponge groups, once the bleeding time had started, it was checked every 10 seconds. If the bleeding did not stop after 40 seconds, it was accepted as a failure. In liquid AHA group, the duration of bleeding was measured using a chronometer and defined as the time (seconds) from wounding until the bleeding stopped. RESULTS: Bleeding time in the heparinized and non-heparinized control groups was over 40 seconds. After applying the sponge form of AHA on the wound area, bleeding time was significantly shortened to less than 20 seconds in both heparinized and non-heparinized rats (p<0.001 for both). The liquid form of AHA stopped bleeding in 5.0±1.2 seconds and 8.0±1.3 seconds in heparinized and non-heparinized groups, respectively. CONCLUSION: AHA is a highly effective topical hemostatic agent in a rat tail hemorrhage model, thus may provide for a unique clinically effective option for control of bleeding during surgical operations or other emergencies. Keywords: Algan Hemostatic Agent; bleeding time; hemorrhage; hemostasis; rat.

INTRODUCTION Immediate control of bleeding during surgical operations or other emergencies is crucial to avoid negative outcomes of

blood loss.[1] Therefore, exogenous hemostatic agents are needed to control the minor or major bleedings from traumatic lacerations, ruptures, fractures, or surgeries.[2] Sever-

Cite this article as: Gedar Totuk ÖM, Güzel ŞE, Ekici H, Kumandaş A, Emre Aydıngöz S, Yılmaz EÇ, et al. Effects of Algan Hemostatic Agent on bleeding time in a rat tail hemorrhage model. Ulus Travma Acil Cerrahi Derg 2020;26:853-858. Address for correspondence: Selda Emre Aydıngöz, M.D. Başkent Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 24 66 66 E-mail: seldaemre71@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(6):853-558 DOI: 10.14744/tjtes.2020.50384 Submitted: 28.11.2019 Accepted: 06.03.2020 Online: 26.10.2020 Copyright 2021 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2021, Vol. 26, No. 6

853

Gedar Totuk et al. Effects of AHA on bleeding time in a rat tail hemorrhage model

al hemostatic products have been shown to be effective in bleeding control.[3–6] These products have different forms, such as powders, liquid, gels, and sheets, according to the area used. While powder and gel forms are preferred to be used on irregular surface areas, sheet-type hemostatic agents are preferred in cases where pressure can be applied in the region.[1] Collagen, oxidized cellulose, and chitosan are currently widely used as hemostatic agents.[3–7] However, during the use of these products, some problems, such as the increased risk of infectious diseases and low pH-induced inflammation, are frequently encountered.[8–12] Thus, there is no consensus on which of these agents has the best hemostatic efficacy and safety profile. As a result, none of the topical hemostatic agents has become dominant over the others, and the search for a more effective and safe topical hemostatic agent continues. Algan Hemostatic Agent (AHA) is a multi-herbal extract containing a standardized amount of Achillea millefolium, Juglans regia, Lycopodium clavatum, Rubus caesius or Rubis fruciosus, Viscum album, and Vitis vinifera, each of which is effective in hemostasis (Patent No: TR2015 0018 A2). AHA exerts a topical hemostatic effect by forming a thick polymeric network which traps blood and blood components passively, and gives rise to a mechanical barrier in the bleeding zone. Its hemostatic efficacy and safety have been shown in various experimental bleeding models.[13–16] Additionally, it has the advantages of low cost and no special storage requirements. However, there is still a need for further preclinical efficacy and safety studies on experimental animal models before proceeding with clinical trials. Rat tail hemorrhage model is one of the most commonly used animal models for preclinical efficacy studies of hemostatic agents.[17–19] In this study, we aimed to evaluate the effects of two different forms of AHA (sponge and liquid) on bleeding time in a rat tail hemorrhage model.

This study was approved by the Institutional Animal Experiments Local Ethics Committee of Kırıkkale University (number, 2018/09) and conformed with the 2015 reprint of the Public Health Service Policy on Humane Care and Use of Laboratory Animals Policy on Humane Care and Use of Laboratory Animals.

Surgical Procedure Rat tail hemorrhage model was created as described previously in the literature.[19] All rats were anesthetized using ketamine hydrochloride (100 mg/kg) and xylazine hydrochloride (10 mg/kg) intramuscularly. After cleaning the rats’ tails with batticon, 4-cm proximal part of the tail was excised using a guillotine (Fig. 1). Once the bleeding started, the area was compressed for 10 seconds with a saline (Fig. 1) or 2 cc AHA-soaked sponge (Fig. 2). In the study groups treated with liquid form of AHA,

(a)

(b)

(c)

Figure 1. In control group, 4-cm proximal part of the rat’s tail was excised using a guillotine under general anesthesia, (a). Once the bleeding started, the area was compressed for 10 seconds with a saline-soaked sponge (b). Bleeding continued for 420 sec and 280 sec after administration of saline-soaked sponge in heparinized and non-heparinized rats, respectively (c).

(a)

(b)

(c)

(d)

(e)

(f)

MATERIALS AND METHODS Animals and Experimental Design Forty-eight Sprague Dawley rats (5–7 weeks old, 180–210 g) were used for this study. Animals fed ad libitum and kept under standard laboratory conditions according to 12-hour dark-light period. The rats were randomly and equally divided into isx groups each containing eight rats: 1) heparin plus saline-soaked sponge (heparinized control), 2) heparin plus AHA-soaked sponge, 3) heparin plus liquid form of AHA, 4) saline-soaked sponge (non-heparinized control), 5) AHAsoaked sponge and 6) liquid form of AHA. Heparin (640 IU/ kg) was administered intraperitoneally three times a day for three days in three heparinized groups. The same amount of saline was administered to three non-heparinized groups. 854

Figure 2. In AHA-soaked sponge group, 4-cm proximal part of the rat’s tail was excised using a guillotine under general anesthesia (a). Once the bleeding started (b), the area was compressed for 10 seconds with a 2 cc AHA-soaked sponge (c). Bleeding stopped within 20 seconds after the administration of AHA-soaked sponge (d-f).

Ulus Travma Acil Cerrahi Derg, November 2021, Vol. 26, No. 6

Gedar Totuk et al. Effects of AHA on bleeding time in a rat tail hemorrhage model

(a)

(b)

The Statistical Package for the Social Sciences software version 22.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. The results were assessed at a 95% confidence interval, and a p-value below 0.05 was assumed to indicate the statistical significance.

(c)

RESULTS (d)

(e)

(f)

Figure 3. In liquid AHA group, 4-cm proximal part of the rat’s tail was excised using a guillotine under general anesthesia (a, b). Once the bleeding started (c), the area was applied with liquid form of AHA without compression (d). Bleeding stopped within 10 seconds after the administration of liquid form of AHA (e, f).

no pressure was applied to the bleeding region and it was left open (Fig. 3).

Bleeding Time The bleeding time was measured as decribed previously.[20] In AHA- or saline-soaked sponge groups, once the bleeding time started, it was checked every 10 seconds. If the bleeding did not stop after 40 seconds, it was accepted as a failure. In liquid AHA group, the duration of bleeding was measured using a chronometer and defined as the time from wounding until the bleeding stopped. At the end of this study, the rats were euthanized with 100 mg/kg intravenous sodium thiopental (Pental Sodyum®, İ.E. Ulagay, İstanbul, Turkey).

While the bleeding from the wound area was continuing in heparinized and non-heparinized saline-soaked sponge group (control) after 40 sec, bleeding stopped within 20 sec in all rats treated with AHA-soaked sponge group (Figs. 1 and 2, Table 1). In heparinized rats, AHA-soaked sponge stopped bleeding within 10 sec in two out of eight rats (25%) and within 20 sec in the remaining six rats (75%) (Fig. 2, Table 1). However, in non-heparinized rats of AHA-soaked sponge group, bleeding stopped within 10 sec in half of the rats (n=4) and within 20 sec in other half of the rats (n=4) (Fig. 2, Table 1). After the application of the sponge on the wound area, bleeding time significantly shortened in both heparinized and non-heparinized rats (p<0.001, Table 1). AHA liquid form stopped bleeding in 8.0±1.3 sec (range 6–10 sec) and 5.0±1.2 sec (range 3–7 sec) in heparinized and non-heparinized groups, respectively (Fig. 3, Table 2). Although liquid AHA and AHA-soaked sponge groups could not be compared statistically, it is possible to say that liquid form of AHA is more effective in bleeding control. Liquid form of AHA controlled bleeding in both heparinized and non-heparinized rats in less than 10 sec, AHA-soaked sponge controlled bleeding in 20 sec in all rats (Fig. 4). Table 2. The mean bleeding time in liquid AHA group Bleeding time

Statistical Analysis

Heparinized (n=8)

This study data were given as number, percentage, mean, and standard deviation. Spearman rank test was used for the comparison of control and AHA-soaked sponge groups in terms of bleeding time category. Due to the difference in bleeding time measurements, liquid AHA and AHA-soaked sponge groups could not be compared.

Liquid form of AHA (n=16) 8.0±1.3 sec (range 6–10 sec)

Non-heparinized (n=8)

5.0±1.2 sec

(range 3–7 sec)

Data are presented as mean±standard deviation (range). Time to bleeding was measured with a chrometer in liquid AHA group. AHA: Algan Hemostatic Agent.

Table 1. The number of rats in the saline- or AHA-soaked sponge groups according to when bleeding stopped

Bleeding time

Saline-soaked sponge (Control) (n=16)

AHA-soaked sponge (n=16)

Heparinized

<10 sec

–

<0.001

<20 sec

–

>40 sec

Non-heparinized

<10 sec

–

<20 sec

–

>40 sec

<0.001

Bleeding was controlled every 10 seconds in both saline- and AHA-soaked sponge groups. AHA: Algan Hemostatic Agent.

Ulus Travma Acil Cerrahi Derg, November 2021, Vol. 26, No. 6

855

Gedar Totuk et al. Effects of AHA on bleeding time in a rat tail hemorrhage model

Number of rats in the study groups according to time of cessation of bleeding 8

Number of rats

7 6

6 5 4

3 2

2 1 0

Saline-soaked sponge (n=8)

AHA-soaked sponge (n=8)

Liquid form of AHA (n=8)

Non-heparinized

In the first administration (10 sec)

Saline-soaked sponge (n=8)

AHA-soaked sponge (n=8)

Liquid form of AHA (n=8)

Heparinized

In the second administration (20 sec)

Figure 4. The number of rats in the study groups according to when bleeding stopped. AHA liquid form stopped bleeding in under 10 seconds in all rats of both heparinized and non-heparinized groups. AHA-soaked sponge stopped bleeding after the first administration in four rats of non-heparined group and in two rats of heparinized group.

DISCUSSION In this study, hemostatic effects of liquid and sponge forms of AHA were evaluated on an experimental rat tail hemorrhage model, and both were effective on bleeding, significantly shortening bleeding time in both heparinized and non-heparinized rats compared to saline control groups. Both liquid and sponge form of AHA stopped the bleeding in under 1020 seconds in the rat tail hemorrhage model. Various materials and chemicals have been evaluated for their hemostatic efficacy in the literature.[21–24] However, there is no consensus on which hemostatic agent is more effective. While some studies found collagen to be a more effective hemostatic agent, others reported that chitin-containing substances were more effective.[21–24] Mean bleeding time of different hemostatics, such as polyurethane, collagen, oxidized regenerated cellulose, gelatin, chitosan added polyurethane, varies between 21 and 28 seconds.[21–24] In the present study, bleeding time after AHA hemostasis was under 10 and 20 seconds in liquid and sponge forms, respectively. In the literature, the bleeding time in healthy Sprague Dawley rats range between 5 and 7 minutes.[19] In one study, bleeding time was 35 seconds after gauze application and 54 seconds in rats without gauze application.[17] Sogut et al.[19] reported that bleeding stoped at 3.29 minutes in heparined rats, and at 1.57 minutes in non-heparinized rats. In consistent with these previous studies, we found that bleeding time was over 40 seconds in non-heparinized and heparinized control groups, respectively. For measurement of bleeding time, we used the rat tail hemorrhage model, a widely accepted experimental model for bleeding studies.[25–27] 856

Some plants have traditionally been used as bleeding stoppers. The mechanism underlying the bleeding-stopping effect of these plants is the astrengenic effect of predominantly tannin type complex polyphenolic phytochemicals.[28] These plants have been shown to shorten the coagulation time and increase the coagulation of platelets in the area of bleeding.[13–16,28] AHA is a newly developed multi-herbal extract containing six hemostatic plants.[13–16] In previous animal studies, AHA has been shown to effectively stop bleeding without any acute, subacute or chronic side effects on tissues.[13–16] Despite these previous studies, it is still necessary to further evaluate the effects of AHA on bleeding before proceding to clinical studies. AHA has been suggested to stop bleeding by physical mechanisms.[13–16] When AHA is applied to the hemorrhage area, it becomes a gel and forms a barrier by surrounding the polymers, blood and blood components in the environment. When AHA used in a moist environment, it quickly polymerizes into a thin elastic film that has high tensile strength and firmly adheres to the tissue on which it is applied. In the present study, AHA liquid form was applied directly onto the bleeding area without any compression. However, AHA-soaked sponge was applied to the bleeding area with a compression for 10 seconds. AHA liquid and sponge forms contain the same amount of AHA. Although compression has a suppressive effect on compression, AHA liquid form was more effective in stopping bleeding than sponge form. The reason for higher efficacy of the liquid form in providing hemostasis may be the deterioration of the hemostasis provided by AHA-soaked sponge during the removal of the sponge. In comparison to the products used for hemostasis in the literature, AHA controlled the bleeding in shorter time in the rat tail hemorrhage model.[17,19,25–27] Given differences in designs and outcomes of studies, such as weight of animals, experience of intestigators, technical equipment, and blood vessel variations, it is clear that comparative studies are needed to demonstrate the superiority of AHA over other plantbased products. Therefore, the main limitation of the study is lack of an active control to compare the hemostatic effectiveness of AHA. Additionally, this study evaluated only the acute effects of AHA. Its chronic effects and safety profile needs to be assessed in further studies. Despite its limitations, the present study is important in terms of demonstrating the hemostatic efficacy of AHA, an easy to apply herbal product, on an accepted experimental model.

Conclusion AHA, a standardized multi-herbal extract, is a highly effective topical hemostatic agent in a rat tail hemorrhage model. AHA may provide for a unique clinically effective option for control of bleeding during surgical operations or other emergencies. Based on the findings of the present experimental study, further comparative clinical studies are needed to confirm its safety and effectiveness on humans. Ulus Travma Acil Cerrahi Derg, November 2021, Vol. 26, No. 6

Gedar Totuk et al. Effects of AHA on bleeding time in a rat tail hemorrhage model

Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Design: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Supervision: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Resource: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Materials: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Data: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Analysis: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Literature search: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Writing: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M.; Critical revision: Ö.M.G.T., Ş.E.G., H.E., A.K., S.E.A., E.Ç.Y., T.K., A.M. Conflict of Interest: None declared. Financial Disclosure: The study drup, Algan Hemostatic Agent (AHA), was provided by The Algan Group Health Services (Algan Group Health Services Import and Export Industry and Trade Limited Company, Istanbul, Turkey). The company had no role in study design, collection, analysis or interpretation of the data, in the writing or decision to submit this manuscript for publication. The manuscript content is solely the responsibility of the authors.

REFERENCES 1. Cothren CC, Moore EE, Hedegaard HB, Meng K. Epidemiology of urban trauma deaths: a comprehensive reassessment 10 years later. World J Surg 2007;31:1507–11. 2. Chiara O, Cimbanassi S, Bellanova G, Chiarugi M, Mingoli A, Olivero G, et al. A systematic review on the use of topical hemostats in trauma and emergency surgery. BMC Surg 2018;18:68. 3. Burkatovskaya M, Tegos GP, Swietlik E, Demidova TN, P Castano A, Hamblin MR. Use of chitosan bandage to prevent fatal infections developing from highly contaminated wounds in mice. Biomaterials 2006;27:4157–64. 4. Hu Z, Zhang DY, Lu ST, Li PW, Li SD. Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Mar Drugs 2018;16:273. 5. Khoshmohabat H, Paydar S, Makarem A, Karami MY, Dastgheib N, Zahraei SAH, et al. A review of the application of cellulose hemostatic agent on trauma injuries. Open Access Emerg Med 2019;11:171–7. 6. Slezak P, Monforte X, Ferguson J, Sutalo S, Redl H, Gulle H, et al. Properties of collagen-based hemostatic patch compared to oxidized cellulose-based patch. J Mater Sci Mater Med 2018;29:71. 7. Leonardis M, Palange A. New-generation filler based on cross-linked carboxymethylcellulose: study of 350 patients with 3-year follow-up. Clin Interv Aging 2015;10:147–55. 8. Bjorenson JE, Grove HF, List MG Sr, Haasch GC, Austin BP. Effects of hemostatic agents on the pH of body fluids. J Endod 1986;12:289–92. 9. Clé-Ovejero A, Valmaseda-Castellón E. Haemostatic agents in apical surgery. A systematic review. Med Oral Patol Oral Cir Bucal 2016;21:e652–7. 10. Hori H, Hattori S, Inouye S, Kimura A, Irie S, Miyazawa H, et al. Analysis of the major epitope of the alpha2 chain of bovine type I collagen in children with bovine gelatin allergy. J Allergy Clin Immunol

Ulus Travma Acil Cerrahi Derg, November 2021, Vol. 26, No. 6

2002;110:652–7. 11. Shilo S, Roth S, Amzel T, Harel-Adar T, Tamir E, Grynspan F, et al. Cutaneous wound healing after treatment with plant-derived human recombinant collagen flowable gel. Tissue Eng Part A 2013;19:1519–26. 12. Tomizawa Y. Clinical benefits and risk analysis of topical hemostats: a review. J Artif Organs 2005;8:137–42. 13. Midi A, Ekici H, Kumandas A, Durmus O, Bodic B, Tiryaki M, et al. Investigation of the effectiveness of algan hemostatic agent in bleeding control using an experimental partial splenectomy model in rats. Marmara Med J 2019;32:27–32. 14. Midi A, Kumandaş A, Ekici H, Arda S, Karahan S, Şimşek AK, et al. Investigation of the effectiveness of algan hemostatic agent in renal venous bleeding model in rats. EJMI 2018;2:129–32. 15. Midi A, Kumandas A, Ekici H, Bayraktar F, Karapirli K, Karahan S, et al. Investigation of the efficacy of Algan Hemostatic Agent in liver laceration model in rats. EJMO 2019;3:37–42. 16. Midi A, Ozyurek HE, Karahan S, Ekici H, Kumandas A, Turkmen I, et al. Investigation of efficacy of the plant based algan hemostatic agent in hepatectomy bleeding model in rats. EJMI 2018;2:195–201. 17. Broekema FI, Oeveren WV, Bos RRM. Analysis of the hemostatic efficacy of polyurethane foam using a novel method to compare topical hemostatic agents in a rat tail-tip model. Int Surg J 2016;3:1551–6. 18. Ryan KL, Cortez DS, Dick EJ Jr, Pusateri AE. Efficacy of FDA-approved hemostatic drugs to improve survival and reduce bleeding in rat models of uncontrolled hemorrhage. Resuscitation 2006;70:133–44. 19. Sogut O, Erdogan MO, Kose R, Boleken ME, Kaya H, Gokdemir MT, et al. Hemostatic efficacy of a traditional medicinal plant extract (Ankaferd Blood Stopper) in bleeding control. Clin Appl Thromb Hemost 2015;21:348–53. 20. Abacıoğlu S, Aydın K, Büyükcam F, Kaya U, Işık B, Karakılıç ME. Comparison of the Efficiencies of Buffers Containing Ankaferd and Chitosan on Hemostasis in an Experimental Rat Model with Femoral Artery Bleeding. Turk J Haematol 2016;33:48–52. 21. Alexander JM, Rabinowitz JL. Microfibrillar collagen (Avitene) as a hemostatic agent in experimental oral wounds. J Oral Surg 1978;36:202–5. 22. Chan MW, Schwaitzberg SD, Demcheva M, Vournakis J, Finkielsztein S, Connolly RJ. Comparison of poly-N-acetyl glucosamine (P-GlcNAc) with absorbable collagen (Actifoam), and fibrin sealant (Bolheal) for achieving hemostasis in a swine model of splenic hemorrhage. J Trauma 2000;48:454–8. 23. Msezane LP, Katz MH, Gofrit ON, Shalhav AL, Zorn KC. Hemostatic agents and instruments in laparoscopic renal surgery. J Endourol 2008;22:403–8. 24. Wagner WR, Pachence JM, Ristich J, Johnson PC. Comparative in vitro analysis of topical hemostatic agents. J Surg Res 1996;66:100–8. 25. Byun JY, Lee S, Lee JI, Yoon HY. Comparison of hemostatic efficacy and cytotoxicity of three ferric subsulfate-and chitosan-based styptics in different formulations using a rat tail bleeding model. Korean J Vet Res 2018;58:119–24. 26. Kihara H, Koganei H, Hirose K, Yamamoto H, Yoshimoto R. Antithrombotic activity of AT-1015, a potent 5-HT(2A) receptor antagonist, in rat arterial thrombosis model and its effect on bleeding time. Eur J Pharmacol 2001;433:157–62. 27. Kosar A, Cipil HS, Kaya A, Uz B, Haznedaroglu IC, Goker H, et al. The efficacy of Ankaferd Blood Stopper in antithrombotic drug-induced primary and secondary hemostatic abnormalities of a rat-bleeding model. Blood Coagul Fibrinolysis 2009;20:185–90. 28. Yeşilada E, Sezik E, Honda G, Takaishi Y, Takeda Y, Tanaka T. Traditional medicine in Turkey IX: folk medicine in north-west Anatolia. J Ethnopharmacol 1999;64:195–210.

857

Gedar Totuk et al. Effects of AHA on bleeding time in a rat tail hemorrhage model

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Algan hemostatik ajan’ın sıçan kuyruk kanama modelinde kanama zamanı üzerine etkisi Dr. Özgün Melike Gedar Totuk,1 Dr. Şevket Ergun Güzel,2 Dr. Hüsamettin Ekici,3 Dr. Ali Kumandaş,4 Dr. Selda Emre Aydıngöz,5 Dr. Enis Çağatay Yılmaz,6 Dr. Taylan Kırdan,7 Dr. Ahmet Midi8 Bahçeşehir Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, İstanbul Sağlık Bakanlığı Adıyaman Kahta Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Adıyaman Kırıkkale Üniversitesi Veterinerlik Fakültesi, Farmakoloji ve Toksikoloji Anabilim Dalı, Kırıkkale 4 Kırıkkale Üniversitesi Veterinerlik Fakültesi, Cerrahi Anabilim Dalı, Kırıkkale 5 Başkent Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Ankara 6 Bahçeşehir Üniversitesi Tıp Fakültesi, 4. Sınıf Öğrencisi, İstanbul 7 Bahçeşehir Üniversitesi Tıp Fakültesi, 5. Sınıf Öğrencisi, İstanbul 8 Bahçeşehir Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Algan hemostatik ajan (AHA), hemostatik etkinliği bilinen Achillea millefolium, Juglans regia, Lycopodium clavatum, Rubus caesius ya da Rubis fruciosus, Viscum album ve Vitis viniferea’yı standardize miktarda içeren bir bitki ekstresidir. Bu çalışmada AHA’nın sıçan kuyruk kanama modelinde kanama zamanı üzerine etkinliğinin değerlendirilmesi amaçlanmıştır. GEREÇ VE YÖNTEM: Kırk sekiz Sprague Dawley sıçan (5–7 haftalık, 180–210 g), altı çalışma grubuna rastgele ve eşit sayıda randomize edildi. Çalışma grupları şunlardır: Heparin + salin (heparinize kontrol), heparin + AHA ile ıslatılmış sünger, heparin + sıvı AHA, salin (heparinize olmayan kontrol), AHA ile ıslatılmış sünger, sıvı AHA. Heparinize gruptaki sıçanlara üç gün boyunca günde üç kez intraperitoneal heparin (640 IU/kg) uygulandı. Kanama modeli oluşturmak için sıçanların kuyrukları kesildi. Çalışma grubuna göre kanama bölgesine salin ile ıslatılmış sünger, AHA ile ıslatılmış sünger ya da sıvı AHA uygulandı. Salin ya da AHA ile ıslatılmış sünger uygulanan gruplarda, kanamanın durumu her 10 saniyede bir kontrol edildi. Kanama 40 saniye sonra hala durmamış ise uygulanan tedavi başarısız kabul edildi. Sıvı AHA uygulanan grupta, kanama süresi kuyruk kesilmesinden kanama durana kadar geçen süre olarak tanımlandı ve kronometre ile ölçüldü. BULGULAR: Heparin uygulanan ve uygulanmayan kontrol gruplarında kanama süresi 40 saniyenin üzerinde kaydedildi. Kanama bölgesine AHA ile ıslatılmış sünger uygulanan heparinize olan ve olmayan sıçanlarda ise kanama süresi anlamlı olarak kısalarak 20 saniyenin altına düştü (her iki grup için de p<0.001). Sıvı AHA uygulanan heparinize olan ve olmayan sıçanlarda kanama süresi sırasıyla 5.0±1.2 saniye ve 8.0±1.3 saniye olarak ölçüldü. TARTIŞMA: AHA, sıçan kuyruk kanama msodelinde yüksek etkinliğe sahip bir hemostatik ajandır. Cerrahi girişimlerde ve acil durumlarda kanama kontrolü sağlanması için kullanılabilecek bir tedavi seçeneği olarak değerlendirilebilir. Anahtar sözcükler: Algan Hemostatik Ajan; hemostaz; kanama; kanama zamanı; sıçan. Ulus Travma Acil Cerrahi Derg 2020;26(6):853-858

858

doi: 10.14744/tjtes.2020.50384

Ulus Travma Acil Cerrahi Derg, November 2021, Vol. 26, No. 6

ORIGIN A L A R T IC L E

Prognostic factors in craniocerebral gunshot wounds: Analysis of 30 patients from the neurosurgical viewpoint Alparslan Kırık, M.D.,

Soner Yaşar, M.D.,

Mehmet Ozan Durmaz, M.D.

Department of Neurosurgery, University of Health Sciences Gülhane Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: Craniocerebral gunshot wounds (CGW) are the most lethal injuries of the cranium. CGW is mostly secondary to military conflicts but may also be seen in civilian life. These injuries also have severe consequences, such as epilepsy, hydrocephalus, infection and late-term cognitive dysfunctions. The present study aims to present our series of CGW and to discuss the prognostic factors and consequences of these injuries. METHODS: The data of patients who were treated in our department for CGW between 2011 and 2019 were retrospectively reviewed in this study. The injury type, wounding site, surgical management and outcomes were analyzed. Radiological evaluation was also performed. RESULTS: Thirty patients were treated with the diagnosis of CGW. All of the patients were male and the mean age was 27.9 years. The frontal lobe was affected in 12 (40%) patients, while temporal lobe in eight, occipital lobe in six, parietal lobe in three, and posterior fossa in one patients. Twenty-three patients underwent surgical treatment, seven patients were treated conservatively. Thirteen (43.3%) patients died despite the treatment. CONCLUSION: Mortality in CGW is high. Ventricular injuries, bihemispheric or midline injuries, perforating injuries, brain stem injuries and low GCS score at admission are prognostic factors for CGW. Appropriate management is mandatory to obtain a better clinical outcome. Keywords: Craniocerebral; gunshot; injury; outcome; surgery.

INTRODUCTION Craniocerebral gunshot wounds (CGW) are increasing medical problems in a military setting, as well as in civilian practice. [1–5] Especially in recent years, the increasing incidents of violence, civil wars and terrorism in cities have made CGW even more important.[6–9] These injuries are the most lethal form of all firearm injuries, and the treatment principles are still controversial.[10,11] Minimal invasive approaches are suggested by many authors, while aggressive surgical methods are also advocated to prevent the mortality of patients.[12–14] Attacks, suicide attempts and accidents are the most common causes of CGW. In wartime or terrorist actions, this type of injuries has the highest mortality and morbidity.[6]

The management of CGW is of paramount importance. Patient’s history, general physical and neurological conditions, and appropriate radiological examinations play a key role in the correct and effective treatment of the patients.[3,15,16] First aid in the field may save the life of patients if it is administered appropriately.[5] Detailed radiological evaluation and intensive care management are the hospital steps of the CGW management.[11] The present study aims to present our experience with the CGW and to determine the possible prognostic factors of such injuries. The clinical, surgical and radiological, as well as surgical data, were collected and analyzed. The results were compared with the current literature.

Cite this article as: Kırık A, Yaşar S, Durmaz MO. Prognostic factors in craniocerebral gunshot wounds: Analysis of 30 patients from the neurosurgical viewpoint. Ulus Travma Acil Cerrahi Derg 2020;26:859-864. Address for correspondence: Alparslan Kırık, M.D. Sağlık Bilimleri Üniversitesi Gülhane Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 304 53 07 E-mail: dr_alper@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):859-864 DOI: 10.14744/tjtes.2020.89947 Submitted: 28.09.2019 Accepted: 11.02.2020 Online: 21.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

859

KÄąrÄąk et al. Prognostic factors in craniocerebral gunshot wounds

MATERIALS AND METHODS

(a)

The data of patients who underwent treatment for CGW were reviewed retrospectively. The clinical presentation, management method, surgical technique and clinical outcomes were analyzed. Ethical approval was obtained for this retrospective study. The demographic data are presented in Table I. Computed tomography (CT) was performed in all patients just after admission to our department. Additional radiological examinations, such as magnetic resonance imaging (MRI) or angiography, were performed in selected patients who had the suspect of abscess or traumatic aneurysm. MRI was not performed in patients with the metal retained fragment. Surgical treatment was performed in patients with active bleeding, open cranial injury and worsening neurological conditions. Debridement of necrotic tissues, stopping the active bleedings, dural repair and skin closure were performed as standard surgical procedures. Deep-seated foreign bodies were left in place if there was no sign of abscess or empyema. Infection prophylaxis was maintained with wide spectrum of antibiotics. Abscesses that were developed in the late phase of treatment were also drained with surgical methods. Cranioplasty was carried out at least one year after the last surgery. Computer-based custom made titanium implants were used for cranioplasty.

RESULTS Thirty patients were treated with the diagnosis of CGW in the Department of Neurosurgery of our institution between 2011 and 2019. All of them were male, and the mean age was 27.9 years, ranging between 19 and 48 years. Twenty-two of them injured in distant cities and transferred to our department after the first aid for further management and eight patients were injured in our city and referred to our department just after the injury. Glasgow coma scale (GCS) score at admission was between three and eight in 16 patients, while GCS score was between nine and 15 in 14 patients. The frontal lobe was the most affected site of the brain, followed by temporal, occipital, parietal lobes and posterior fossa (Figs. 1 and 2) (Table 2). Surgical treatment was in 23 (76.6%) patients, while seven patients underwent conservative (wound closure only) management. Perforating injuries were observed in five patients (Figs. 3 and 4). Three of the seven pa-

(b)

Figure 1. (a) A patient with right orbitofrontotemporal fracture secondary to the explosion. (b) 3-D CT scan shows right orbital perforation and fracture lines.

(a)

(b)

Figure 2. (a, b) Axial CT scans of a patient with right occipital gunshot wound secondary to bullet penetration. The metal artefact is obvious.

tients with conservative treatment had a diffuse brain injury, swelling or herniation at the time of admission (Fig. 5), while the other four patients had a tangential injury with minimal Table 2. Sites of the injury Site Number Frontal lobe

Temporal lobe

Occipital lobe

Parietal lobe

Posterior fossa

Table 1. The demographic and surgical features of the patients Weapon

Number

Mean age (years)

Male/Female

Military/Civilian

Surgery/Conservative

Death

Rifle (bullet)

20.3

4/0

3/1

Handgun (bullet)

1/0

0/1

Handmade explosive (shrapnels)

25.8

25/0

21/4

20/5

Total

30 27.9 30/0 25/5

860

23/7 13

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

KÄąrÄąk et al. Prognostic factors in craniocerebral gunshot wounds

(a)

(b)

Figure 6. (a) Intraoperative view of a patient with CGW. The necrotic brain tissue (*) was herniated through the dura mater defect. (b) The necrotic brain tissue was removed and the duraplasty was performed with synthetic dural substitute. Figure 3. Axial CT scan of a patient with bihemispheric CGW.

(a)

(b)

formed in 20 patients (Fig. 6, Table 3). Cerebrospinal fluid (CSF) fistula was observed in two patients after surgery and treated conservatively. Postoperative wound infection was observed in five patients and treated using antibiotics. Five patients received anticonvulsive treatment due to the development of posttraumatic epilepsy (Table 4). Eight patients underwent custom-made computer-based cranioplasty with titanium implants.

DISCUSSION

Figure 4. (a) A patient with perforating CGW secondary to the suicide attempt. (b) Axial CT scan shows the entrance and exit points of the bullet wound trajectory and bone fragments into the cranium.

(a)

(b)

We presented the results of 30 patients with CGW. The demographic, radiological and surgical data were shared. Our mortality rate was 43.3% and the most common causes of death were diffuse brain injury and low GCS score at admission. CGW causes high mortality and morbidity due to their destructive properties on the central nervous system (CNS) Table 3. Types of the surgical management Surgery types

Number

Only wound closure

Necrotic tissue debridement with intact dura mater

Duraplasty 12 Debridement+duraplasty 8 Figure 5. (a) A patient with left fronto-orbital CGW secondary to landmine explosion). (b) 3-D CT scan showed multiple shrapnels and fracture lines on the cranium.

cerebral contusion and GCS score was 15 at admission. Thus, there was no need for surgery. Thirteen (43.3%) patients died despite surgical or medical treatment. Ten of them had GSC score at admission between three and eight, three patients had a diffuse brain injury and underwent decompressive craniectomy. Duraplasty was perUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Table 4. Outcome and complications of the 30 patients with craniocerebral gunshot wounds Outcome Number Died 13 Cerebrospinal fluid fistula

Infection 5 Epilepsy 5

861

Kırık et al. Prognostic factors in craniocerebral gunshot wounds

structures. Patients with CGW need special care and their treatment is quite challenging.[17–19] These injuries are classified according to the type of weapon and the type of injury. For example, military-type penetrating injuries more often arise from shrapnel and high-speed projectiles, while civilian-type penetrating injuries mostly arise from low-velocity guns.[5,6,12,17] In addition to the kinetic energy of the bullet or wounding body, the shape of the wounder, the angle of incidence, and the tissues through which it passes are effective on the penetration of the wounding body.[17] The frequency of CGW varies according to the geographical area, socioeconomic conditions and cultural differences.[17] The incidence of CGW is higher, especially in societies where guns are easy to acquire and violence tendencies are at the forefront. CGW accounts for 35% of deaths under the age of 45 from brain damage. We should note that 2/3 of these patients die before being hospitalized.[6,9,17] In the United States, the annual mortality rate from head injuries due to gunshot wounds is 2–4/100 000.[10,17] It is also important which region of the brain is affected in such injuries. Although the frontal lobe is usually the most commonly affected area, the posterior fossa and brain stem are the least affected areas.[2,10,20] In our series, the frontal lobe is mostly injured, this site was followed by the other brain lobes. Ventricular and brain stem injuries are the most lethal forms of CGW.[10,11,20] Radiology is an important step in patient evaluation with CGW. Plain x-rays and CT scans are crucial for the determination of retained bone and metal fragments (Fig. 2). Initial CT scan shows brain tissue injury, hemorrhages, fragments, edema and infection if performed in the late period of injury.[7,17] In case of injuries with landmines or grenades, small shrapnels cause significant injuries in the brain and these particles can be easily detected by CT scans.[21] However, metal fragments may also cause significant artefacts that may obscure possible hemorrhages in the brain. In such cases, plain skull x-rays are helpful to determine the size of the metal fragment. MRI is usually performed in the late period of injury to determine the size of brain damage, the presence of late brain abscess, or any focus or epilepsy.[4,18,22] It should not be forgotten that MRI is contraindicated in patients with metal fragments within the skull. Penetrating injuries usually arise from low-speed projectiles, such as shrapnels (Figs. 3, 4). Some of the kinetic energy of the projectile is transferred to the brain and some of it is absorbed by the skull.[6,17] These injuries may result in focal brain contusion, laceration or intracerebral hematoma. Dispersion of bullet fragments or fractured bone fragments into the brain is rare. The prognosis is better in these injuries because brain damage is relatively limited. Landmine and grenade injuries in military setting cause penetrating CGW (Fig. 5). However, perforating injuries affect both sides of the head and is the most destructive form of CGW.[6,17] They usually occur with high-speed projectiles or close-up CGW with a suicide 862

attempt. The exit point of the bullet is larger than the entry point. Exploding and disintegrating bone fragments cause extensive neuronal damage in the brain. Shock waves affect the brain stem, causing impaired respiratory and circulatory system functions and death.[17] In our series, 25 patients had a penetrating type of CGW and five patients had a perforating type of the CGW. Significant brain damage was observed in our patients with perforating CGW and low GCS score was the common feature of these patients. Management of each patient should be done based on the clinical, physical and radiological evaluation.[6] Open wounds with active bleeding and brain damage should be operated as soon as possible to save the life of the patient.[1,2,11,17] Aggressive surgical treatment is not helpful in patients with GCS score 3 and who have impaired brain stem functions.[17] Debridement of necrotic brain tissues and stopping the active bleedings are the main aims of the surgery. Foreign bodies or bone fragments on the brain surface are also collected and the dura edges can be found with some amount of craniectomy.[10,11,15] This is necessary for proper closure of dura mater or duraplasty (Fig. 6). Artificial materials or allografts may be used for dural closure. This prevents a possible CSF leak and infection after surgery.[10,17] In addition, tetanus prophylaxis should be performed associated with prophylactic antibiotics and anticonvulsive therapy.[8,23] The standard surgical treatment of intracranial hypertension is external ventricular drainage (EVD). If intracranial pressure is high despite EVD, the damaged frontal or temporal lobe can be partially excised or a decompressive craniectomy may be performed. [24] Prophylactic antibiotics can be continued for 10–14 days and anticonvulsive therapy for 6–12 months.[5,17,19,22,25] In our series, we operated 23 patients with CGW. We performed the afformentioned methods and obtained satisfactory clinical outcomes. Epilepsy, intracranial infection and sinking skin flap syndrome are late complications of CGW.[6,17,26] Anticonvulsive therapy may be administered after surgery or after the first seizure of the patient, which depends on the surgeon and electrophysiological findings after discharge. Antibiotics may be continued if there are contrast-enhancing lesions in the brain. [22,27] Headache, neurological deficits and seizures may be the symptoms of sinking skin flap syndrome in patients with large cranial defects.[3,10,17,22,28] These defects should be closed using synthetic materials, such as methyl methacrylate, porous polyethylene or titanium. In addition, this closure should be delayed until the first year of injury due to the dirty nature of CGW. In our series, we performed custom-made titanium cranioplasty in eight patients with large cranium defects and obtained good cosmetic results. These cranioplasty materials were manufactured in the medical design and production center of our institution. Prediction of prognosis is important in the management of the CGW. In all studies, the GCS score was found to be the Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Kırık et al. Prognostic factors in craniocerebral gunshot wounds

most important factor in determining the prognosis of the patient and the effectiveness of surgical treatment.[10,11,15,17,19,20,29] Pupillary changes, systemic shock, presence of infection, internal organ injuries and coagulation disorders increase the mortality of patients with higher GCS score.[24] Ventricular injuries, bihemispheric or midline injuries, large vessel injuries, and brain stem injuries increase the mortality of patients with CGW.[17,18,20,23,29–31] Orbital and maxillofacial injuries may be associated with CGW and must be evaluated precisely by the surgeon to avoid further morbidities.[6,14,17,32] The major limitations of our study are the lack of long term follow-up period and the small number of the patient population.

Conclusion In the management of the CGW: 1) Rapid neurological and radiological evaluation should be performed. 2) Intracranial hematomas should be evacuated with the debridement of necrotic tissues and haemostasis should be provided as soon as possible. 3) Easily accessible superficial or embedded bone and bullet fragments and foreign bodies should be removed. 4) If possible, the dura should be closed primarily or by using autografts or artificial materials. 5) In case of postoperative CSF leakage, lumbar drainage should be applied immediately, and if the leakage does not stop within a few days, the patient should be re-operated, 6) Rehabilitation of patients with neurological deficits should be started as soon as possible. 7) Cranioplasty should be planned at least 12 months after the injury and custom-made implants should be preferred to obtain better cosmetic results. 8) Ventricular injuries, bihemispheric or midline injuries, perforating injuries, brain stem injuries and low GCS scale at admission are prognostic factors for the CGW. Ethics Committee Approval: Turkish General Staff Gülhane Military Medical Academy Command Ethics Committee granted approval for this study (date: 08.06.2016, number: 2016/331). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.K.; Design: A.K., S.Y.; Supervision: M.O.D.; Materials: S.Y.; Data: A.K., S.Y.; Analysis: S.Y.; Literature search: M.O.D.; Writing: A.K.; Critical revision: M.O.D. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Alvis-Miranda HR, Adie Villafañe R, Rojas A, Alcala-Cerra G, Moscote-Salazar LR. Management of Craniocerebral Gunshot Injuries:

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

A Review. Korean J Neurotrauma 2015;11:35–43. 2. Carey ME. Analysis of wounds incurred by U.S. Army Seventh Corps personnel treated in Corps hospitals during Operation Desert Storm, February 20 to March 10, 1991. J Trauma 1996;40:S165–9. 3. George ED, Dagi TF. Military penetrating craniocerebral injuries. Applications to civilian triage and management. Neurosurg Clin N Am 1995;6:753–9. 4. Kong V, Odendaal J, Sartorius B, Clarke D, Brysiewicz P, Jerome E, et al. Civilian cerebral gunshot wounds: a South African experience. ANZ J Surg 2017;87:186–9. 5. Stone JL, Lichtor T, Fitzgerald LF. Gunshot wounds to the head in civilian practice. Neurosurgery 1995;37:1104–12. 6. Izci Y, Tehli O. Cranial and Spinal Cord Injuries in Terror and War [Article in Turkish].Okmeydanı Tıp Derg 2017;33:21–39. 7. Jamous MA. Outcome of Craniocerebral Penetrating Injuries: Experience from the Syrian War. J Neurol Surg A Cent Eur Neurosurg 2019;80:345–52. 8. Joubert C, Sellier A, Morvan JB, Beucler N, Bordes J, Dagain A. Vacuum-assisted closure (VAC) for craniocerebral wounds in severely injured patients: technical note of a damage control procedure. J R Army Med Corps 2019;165:e1. 9. Secer HI, Gonul E, Izci Y. Head injuries due to landmines. Acta Neurochir (Wien) 2007;149:777–82. 10. Izci Y, Kayali H, Daneyemez M, Koksel T, Cerrahoglu K. The clinical, radiological and surgical characteristics of supratentorial penetrating craniocerebral injuries: a retrospective clinical study. Tohoku J Exp Med 2003;201:39–46. 11. Izci Y, Kayali H, Daneyemez M, Koksel T. Comparison of clinical outcomes between anteroposterior and lateral penetrating craniocerebral gunshot wounds. Emerg Med J 2005;22:409–10. 12. Bakir A, Temiz C, Umur S, Aydin V, Torun F. High-velocity gunshot wounds to the head: analysis of 135 patients. Neurol Med Chir (Tokyo) 2005;45:281–7. 13. Coşar A, Gönül E, Kurt E, Gönül M, Taşar M, Yetişer S. Craniocerebral gunshot wounds: results of less aggressive surgery and complications. Minim Invasive Neurosurg 2005;48:113–8. 14. Solmaz I, Kural C, Temiz C, Seçer HI, Düz B, Gönül E, et al. Traumatic brain injury due to gunshot wounds: a single institution’s experience with 442 consecutive patients. Turk Neurosurg 2009;19:216–23. 15. Joseph B, Aziz H, Pandit V, Kulvatunyou N, O’Keeffe T, Wynne J, et al. Improving survival rates after civilian gunshot wounds to the brain. J Am Coll Surg 2014;218:58–65. 16. Kong VY, Oosthuizen GV, Sartorious B, Bruce JL, Laing GL, Weale R, et al. Validation of the Baragwanath mortality prediction score for cerebral gunshot wounds: the Pietermaritzburg experience. Eur J Trauma Emerg Surg 2018;44:615–20. 17. Gonul E, Secer HI, Izci Y. Cranial gunshot wounds. In: Gonul E, Izci Y, editors. Gunshot Injuries in Neurosurgery. Ankara, Bulus Tasarim; 2013.p.45–78. 18. Hazama A, Ripa V, Kwon CS, Abouelleil M, Hall W, Chin L. Full Recovery After a Bihemispheric Gunshot Wound to the Head: Case Report, Clinical Management, and Literature Review. World Neurosurg 2018;117:309–14. 19. Kaufman HH. Care and variations in the care of patients with gunshot wounds to the brain. Neurosurg Clin N Am 1995;6:727–39. 20. Erdogan E, Izci Y, Gonul E, Timurkaynak E. Ventricular injury following cranial gunshot wounds: clinical study. Mil Med 2004;169:691–5. 21. Karaca MA, Kartal ND, Erbil B, Öztürk E, Kunt MM, Şahin TT, et al. Evaluation of gunshot wounds in the emergency department. Ulus Trav-

863

Kırık et al. Prognostic factors in craniocerebral gunshot wounds ma Acil Cerrahi Derg 2015;21:248–55. 22. Janković S, Bradarić N, Busić Z, Dujić Z, Andelinović S, Primorac D. Early intracranial infections after brain missile injuries--the role of computer tomography in diagnosis and treatment. Acta Med Croatica 1997;51:233–7. 23. Wei LF, Wang SS, Jing JJ, Zheng ZC, Gao JX, Liu Z, et al. Surgical therapy for craniocerebral firearm injury. Turk Neurosurg 2013;23:491–7. 24. Roberts SA, Toman E, Belli A, Midwinter MJ. Decompressive craniectomy and cranioplasty: experience and outcomes in deployed UK military personnel. Br J Neurosurg 2016;30:529–35. 25. Melada A, Marcikić M, Mrak G, Stimac D, Sćap M. Cerebrospinal fluid fistula as a consequence of war head injury. Mil Med 2002;167:666–70. 26. Ozkan U, Kemaloğlu S, Ozateş M, Aydin MD. Analysis of 107 civilian craniocerebral gunshot wounds. Neurosurg Rev 2002;25:231–6.

27. Abdolvahabi RM, Dutcher SA, Wellwood JM, Michael DB. Craniocerebral missile injuries. Neurol Res 2001;23:210–8. 28. Karasu A, Cansever T, Sabanci PA, Kiriş T, Imer M, Oran E, et al. Craniocerebral civilian gunshot wounds: one hospital’s experience. [ Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2008;14:59–64. 29. Ecklund JM, Sioutos P. Prognosis for gunshot wounds to the head. World Neurosurg 2014;82:27–9. 30. Ansari SA, Panezai AM. Penetrating craniocerebral injuries: an escalating problem in Pakistan. Br J Neurosurg 1998;12:340–3. 31. Yildizhan A, Paşaoğlu A, Gök AV, Aral O. Surgical management of craniocerebral gunshot wounds. Neurosurg Rev 1992;15:45–50. 32. Gönül E, Akbörü M, Izci Y, Timurkaynak E. Orbital foreign bodies after penetrating gunshot wounds: retrospective analysis of 22 cases and clinical review. Minim Invasive Neurosurg 1999;42:207–11.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kranyoserebral ateşli silah yaralanmalarında prognostik faktörler: Nöroşirürji bakış açısından 30 hastanın analizi Dr. Alparslan Kırık, Dr. Soner Yaşar, Dr. Mehmet Ozan Durmaz Sağlık Bilimleri Üniversitesi Gülhane Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Ankara

AMAÇ: Kranyoserebral ateşli silah yaralanmaları (KASY), kranyumun en ölümcül yaralanmalarıdır. Çoğunlukla askeri çatışmalara sekonderdir. Bu yaralanmaların ayrıca epilepsi, hidrosefali, enfeksiyon ve geç dönem bilişsel işlev bozuklukları gibi ciddi sonuçları da vardır. Çalışmamızın amacı, kliniğimizin KASY serisini sunmak ve bu yaralanmaların sonuçlarını ve prognostik faktörlerini tartışmaktır. GEREÇ VE YÖNTEM: 2011–2019 yılları arasında bölümümüzde KASY tanısı ile tedavi edilen hastalar geriye dönük olarak incelendi. Yaralanma tipleri, yerleri, cerrahi tedavileri ve sonuçları analiz edildi. Radyolojik değerlendirme de yapıldı. BULGULAR: Otuz hasta KASY tanısı ile tedavi edildi. Bunların hepsi erkekti ve yaş ortalaması 27.9 idi. Frontal lob 12 (%40) hastada etkilenirken, sekiz hastada temporal lob, altı hastada oksipital lob, üç hastada parietal lob ve bir hastada posterior fossa etkilendi. Yirmi üç hastaya cerrahi tedavi uygulandı. On üç hasta (%43.3) cerrahi veya tıbbi tedaviye rağmen kaybedildi. TARTIŞMA: Kranyoserebral ateşli silah yaralarında ölüm oranı yüksektir. Ventriküler yaralanma, bihemisferik yaralanma, perforan yaralanma, beyin sapı hasarı ve başvuru anında düşük GKS skoru prognostik faktörlerdir. Daha iyi klinik sonuçlar elde etmek için uygun ve doğru hasta yönetimi zorunludur. Anahtar sözcükler: Ateşli silah; cerrahi; kranioserebral; sonuç; yaralanma. Ulus Travma Acil Cerrahi Derg 2020;26(6):859-864

864

doi: 10.14744/tjtes.2020.89947

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

Evaluation of complications in patients with open fractures of the upper and lower extremity treated with internal fixation after the external fixation Mahmut Bilir, M.D.,1

Sezgin Bahadır Tekin, M.D.2

Department of Orthopedics and Traumatology, Adıyaman University Training and Research Hospital, Adıyaman-Turkey

Department of Orthopedics and Traumatology, Dr. Ersin Arslan Training and Research Hospital, Gaziantep-Turkey

ABSTRACT BACKGROUND: Open fractures constitute an important mortality and morbidity cause among all musculoskeletal system injuries and bring along many social and economic problems. The cost occurring due to both long treatment duration and the delay in returning to work made these conditions more complicated. The present study aims to evaluate of the complications which may occur in cases with an application of internal fixation following external fixator in upper and lower extremity open fractures retrospectively. METHODS: Forty-nine patients, who applied to the emergency service between 2007 and 2013, participated in this study. Thirty-two of these patients consisted of the patients to whom external fixator was first placed, and then internal fixation was performed by us, while 17 patients were treated in another center with the external fixator, and then their treatments were performed by us. All patients’ injury mechanism, duration of follow-up with an external fixator, whether debridement was performed after external fixator, the period between external fixation and internal fixation, pin site infection, duration of the union, delayed union, nonunion, whether bone graft was used during internal fixation, internal fixation type, reoperation, development of osteomyelitis and follow-up parameters were recorded. RESULTS: Results were evaluated separately for radius, humerus, tibia and femur fractures. Of the 49 patients, 39 were male, and 10 were female. Mean follow-up time for tibia 28.6 months, for femur 34, for humerus 26.9, for Radius 27 months. Of the 49 patients who participated in this study, 15 applied with upper extremity (11 humeri, 4 Radius) injury and 34 applied with lower extremity (25 tibias, 9 femora) injury. Of the 49 patients, 32 had pin tract infection, 11 had nonunion, 11 had delayed union, two had osteomyelitis. CONCLUSION: Open fractures are always hard to treat. After external fixation to the internal fixation process have some complications, phsycians should be aware of all these problems and plan according to the situation. Keywords: External fixation, gunshot; internal fixation; open fracture.

INTRODUCTION Open fractures frequently occur as a result of high-energy traumas. Therefore, they are cases open to many complications, such as soft tissue problems, deep infections and nonunion. With the rapid development of societies and industry, the incidence of open fractures is increasing each passing day. [1] Open fractures are not only characterized by bone tissue injury but also a type of trauma in which soft tissues, such as

skin, muscle, nerve and vein, can be injured.[2] The presence of additional injuries makes the treatment even more complicated. Recent studies have shown that infection rates following closed fractures are 1%, while this rate may range between 15–55% in open fractures.[3,4] These rates clearly show that open fractures need to contain severe treatment principles. Questions, such as what to do when they first arrive, what

Cite this article as: Bilir M, Tekin SB. Evaluation of complications in patients with open fractures of the upper and lower extremity treated with internal fixation after the external fixation. Ulus Travma Acil Cerrahi Derg 2020;26:865-869. Address for correspondence: Sezgin Bahadır Tekin, M.D. Dr. Ersin Arslan Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, Gaziantep, Turkey Tel: +90 342 - 221 07 00 E-mail: sezginbahadirtekin@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):865-869 DOI: 10.14744/tjtes.2020.80236 Submitted: 04.05.2019 Accepted: 01.05.2020 Online: 21.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

865

Bilir et al. Evaluation of complications after external fixation to internal fixation

nal fixator, whether debridement was performed after external fixator, the period between external fixation and internal fixation, pin site infection, duration of the union, delayed union, nonunion, whether bone graft was used during internal fixation, internal fixation type, reoperation, development of osteomyelitis and follow-up parameters were recorded.

kind of a treatment method should be determined, when to treat and which implant should be used, are in the minds of all clinicians. In addition, the high complication rates seen in these patients prolong the duration of hospital stay and lead to an economically increased cost. In this study, our aim is to investigate the complications that occur after the treatment of the patients with open fractures who applied to our clinic and to provide the literature with the data regarding how to manage them.

This study was conducted after obtaining the approval of the ethics committee of Gaziantep University.

RESULTS

MATERIALS AND METHODS

Of the 49 patients who participated in this study, 15 applied with upper extremity (11 humeri, 4 Radius) injury and 34 applied with lower extremity (25 tibias, 9 femur) injury. Of the 49 patients, 39 were male, and 10 were female. Mean follow-up time for tibia 28.6 months, for femur 34, for humerus 26.9, for Radius 27 months. Of the 49 patients who participated in this study, 15 applied with upper extremity (11 humeri, 4 radius) injury and 34 applied with lower extremity (25 tibias, 9 femora) injury. Of the 49 patients, 32 had pin tract infection (65%), 11 had nonunion (22%), 11 had delayed union (22%), two had osteomyelitis (4%). Separated patients demographics can be seen in Table 1.

Forty-nine patients, who applied to the emergency service between 2007 and 2013, participated in this study. Thirty-two of these patients consisted of the patients to whom external fixator was first placed and then internal fixation was performed by us, while 17 patients were treated in another center with an external fixator and then their treatments were performed by us. All patients were firstly evaluated in the emergency service. In all patients admitted with an open fracture, isotonic sodium and debridement were applied in the emergency service. Nerve, vascular and soft tissue injuries were noted. Consultations were demanded by the relevant departments. All patients were evaluated for antibiotics and tetanus prophylaxis in the emergency service. According to Gustilo-Anderson, cefazolin prophylaxis was given to Type 1 and 2 fractures, and additionally, aminoglycoside prophylaxis was given to Type 3 open fractures. Tetanus prophylaxis was performed in all patients. The patients were grouped according to the region with fractures in the lower extremity and upper extremity. All patients were directed to the relevant unit for their radiographies after the first debridement procedure and antibiotic prophylaxis in the emergency service. All patients received antibiotics for three days following the external fixator in line with the open fracture classifications. Then, internal fixation was performed in the patients deemed appropriate. All patients’ injury mechanism, duration of follow-up with an exter-

Tibia The mean age of patients, who had open tibial fracture and underwent internal fixation following external fixator, was 28.6 (9–50), seven were female, and 18 were male. The patients were followed for 18.1 (5–38 months) months on average. Nine patients were operated due to motor accident, 10 patients firearm injuries, four patients occupational accidents and two patients falling down from the height. Four patients were classified according to Gustilo-Anderson, two patients applied due to Type two injuries, eight patients 3A, 9 patients Type 3B and six patients Type 3C. The mean duration between the arrival of the patients and the external fixator application was 2.1 days (0–4).

Table 1. Patients demographics according to fracture sides Mean age Gender Follow period Etiology Ef to If

Tibia Femur Humerus Radius 28.6 (9–50)

34 (6–76)

26.9 (15–48)

27 (24–34)

18m/7f

8m/1f

9m/2f

18.1 (5–38)

13.1 (1–36)

10.6 (2–24)

9.5 (5–16)

Mixed Mixed Mixed Mixed 12.5 days

9.8 days

5.81 days

16.2 days

Pin tract infec.

18 patients

Nonunion

6 patients

Delayed union

9 patients

–

Osteomyelitis

2 patients

–

866

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Bilir et al. Evaluation of complications after external fixation to internal fixation

The mean transition time to internal fixation following external fixation was 12.5 days.

ries underwent soft tissue reconstruction. Osteomyelitis did not develop in any patient.

Fifteen of the patients who underwent internal fixation were treated with an intramedullary nails and 10 with plate screw fixation.

Humerus

Ten patients had tibial shaft fractures, seven patients had plateau fractures and eight patients had tibial distal fractures. Bone graft was used in 22 patients with internal fixation. Before internal fixation, 18 patients had a pin site infection, while seven patients did not have a pin site infection. Debridman were performed on 10 patients before internal fixation. In the follow-ups after internal fixation, nonunion was observed in six patients. Three patients were excluded from follow-up since they did not visit the hospital for their follow-ups. The other three patients were reoperated. Uneventful union was observed in 16 patients (mean: 3.9 months). Delayed union was observed in 9 patients (mean union duration: 6.2 months). Soft tissue reconstruction and vascular repair were performed in the patients with Type 3C. Osteomyelitis developed in two patients.

Femur The mean age of the patients who had open femoral fracture and underwent internal fixation after the external fixator was 34 (6–76) and eight patients were male and one patient was female. The mean follow-up duration was 13.1 months (1–36). Four patients were operated due to motorcycle accidents and five patients were operated due to firearm injury. Two patients were classified according to Gustilo-Anderson, two patients applied due to Type 2 injuries, three patients 3A, two patients Type 3B and 2 patients Type 3C.

The mean age of the patients who had open humerus fracture and underwent internal fixation after an external fixator, was 26.9 (15–48) and nine patients were male and two patients were female. The mean follow-up duration was 10.6 months (2–24 months). Five patients were operated due to car accidents, and five patients were operated due to firearm injury. Two patients applied according to Gustilo-Anderson, two patients applied due to Type 2 injuries, three patients 3A, two patients Type 3B and two patients Type 3C. The mean duration between the arrival of the patients and the external fixator application was 2.1 days (0–3). The mean transition time to internal fixation following external fixation was 5.81 days (0–15). Plate screw fixation was performed in all patients who underwent internal fixation. All patients had a humerus shaft fracture. Bone graft was used in eight patients with internal fixation. Before internal fixation, four patients had pin site infection, while five patients did not have a pin site infection. Debridman were performed on four patients before internal fixation. In the follow-ups after internal fixation, nonunion was observed in two patients. They were reoperated. Uneventful union was observed in eight patients (mean: 4.7 months). Delayed union was observed in two patients. No patient required vascular repair and soft tissue reconstruction was not performed. Osteomyelitis did not develop in any patient.

Radius

The mean duration between the arrival of the patients and the external fixator application was 2.1 days (0–4). The mean transition time to internal fixation following external fixation was 9.8 days. Two of the patients who underwent internal fixation were treated with the intramedullary nail and two with plate screw fixation. Eight patients had femoral shaft fracture, and one patient had a proximal femoral fracture.

The mean age of the patients who had open radius fractures and underwent internal fixation after the external fixator was 27 (24–34) and four patients were male. The mean follow-up duration was 9.5 months (5–16 months). Two patients were operated due to occupational accident and two patients were operated due to firearm injury. Two patients were classified according to Gustilo-Anderson, two patients Type 3A and two patients Type 3B. The mean duration between the arrival of the patients and external fixator application was 2.1 days (0–3). The mean transition time to internal fixation following external fixation was 16.2 days (0–90).

Bone graft was used in seven patients with internal fixation. Before internal fixation, six patients had a pin site infection, while three patients did not have a pin site infection. Debridman were performed on six patients before internal fixation. In the follow-ups after internal fixation, nonunion was observed in one patient. Uneventful union was observed in eight patients (mean: 4.7 months). No patient had a delayed union. Vascular repair was performed in the patients with Type 3C injury, and four patients with Type 3B and 3C inju-

Plate screw fixation was performed in all patients who underwent internal fixation. Two patients had a Radius shaft and two patients had a proximal Radius fracture. Bone graft was used in four patients with internal fixation. Pin site infection was observed in four patients before internal fixation. In the follow-ups after internal fixation, nonunion was observed in two patients. They were reoperated. No debridement was performed before internal fixation. Uneventful union was observed in two patients (mean: 4.7 months). Delayed union

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

867

Bilir et al. Evaluation of complications after external fixation to internal fixation

was not observed. No patient required vascular repair and soft tissue reconstruction was not performed. Osteomyelitis did not develop in any patient.

DISCUSSION Open fractures are generally accompanied by complications at a high rate and significantly cause morbidity. The current concept in the treatment of open fractures is the immediate classification of the injury, early antibiotic prophylaxis, early wound debridement and fixation.[5] Following the above-mentioned steps, additional operations are needed in these patients for the final treatment. In this respect, our aim is to investigate the complications emerging in the cases who received first arrival treatment, followed and underwent internal fixation. In our study, open fractures of both the upper and lower extremities were examined. Our treatment method in these fractures progressed in the light of the current literature and complications that might arise were standardized. Gustilo-Anderson classification is used in the classification of open fractures. Type 3 fractures involve an increased risk of complications, and this situation has generally been evaluated independently from implantation.[6,7] In our study, the patients were classified according to the Gustilo-Anderson classification and treatments were designed accordingly. Type 3C injuries required further treatments, and the rates of complications were higher compared to other open fractures. Emergency medical intervention is very important in open fractures. Early debridement of the fracture and antibiotherapy should be performed early. However, there are articles in the literature stating that this situation is not very significant. [8â&#x20AC;&#x201C;11] On the contrary, there is also information reporting that early debridement reduces the risk of future infections and has positive effects on recovery.[12] In our study, early irrigation and debridement were performed in our patients in the emergency service and the necessary antibiotherapies were applied. According to us, the reflection of this situation on infection parameters is also positive. In general, a small number of patients had permanent infection (i.e., osteomyelitis). This situation can be associated with many factors. We think that it cannot be explained only with first arrival debridement and antibiotherapy, and the first injury form of the patient has an effect on this issue. It was documented by Harris et al.[13] that complex and high-energy open fractures are associated with severe complications. It has been reported that the most commonly seen complication is nonunion (31.5%) in the patients who are in the stage of extremity recovery and wound infection is then observed. In our study, although we did not struggle with nonunion considerably, the infection was an important problem. The low rate of nonunion can be attributed to the 868

success of internal fixation and the use of additional methods such as grafting. Deep wound infection is among the most important problems of open fractures, and the wound environment is very suitable for the spread of bacteria.[14,15] This rate can reach 52% in Gustilo Type 3B injuries.[16] The place of antibiotherapy is very important in the accurate treatment of these patients. Recently, there are studies reporting that final fixation and flap application in one session reduces the risk of osteomyelitis and deep infection in patients with Type 3B-C injury. [17,18] In our study, the final fixation was always performed in two stages. As the correct method, we first performed external fixator treatment. After the risk of infection was removed and soft tissues were closed, we performed the final fixation; however, there are still patients in our series with osteomyelitis in all fracture groups. In our study, there are some missing points. First of all, this is a retrospective study. In this study, our patients consisted of a heterogeneous group. It was not investigated whether the parameters, such as lifestyle, nutritional habits, weight, smoking and additional diseases of the patients, affected the results. On the other hand, we only scanned the complications. Functional scores of the patients are not among the parameters that we investigated. This may be the subject of further study. The number of the patients constituting the upper extremity is very low. A more comprehensive study could be conducted by increasing the number, but the low number of patients with open fractures in the upper extremity can be shown as a reason for this.

Conclusion Open fractures are difficult to treat and open to any complication. Obtaining preliminary information regarding the complications that can be seen while treating these injuries can make it easier to take precautions in advance and enable them to take different steps in treatment management. Ethics Committee Approval: Gaziantep University Faculty of Medicine Ethics Committee granted approval for this study. (date: 17.09.2013/310). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.B.; Design: M.B.; Supervision: M.B.; Data: M.B.; Analysis: M.B.; Literature search: M.B.; Writing: S.B.T.; Critical revision: S.B.T. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Court-Brown CM, McBirnie J. The epidemiology of tibial fractures. J Bone Joint Surg Br 1995;77:417â&#x20AC;&#x201C;21. 2. Court-Brown CM, Bugler KE, Clement ND, Duckworth AD, McQueen

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Bilir et al. Evaluation of complications after external fixation to internal fixation

4. 5.

6. 7.

10. 11.

MM. The epidemiology of open fractures in adults. A 15-year review. Injury 2012;43:891–7. Morgenstern M, Kühl R, Eckardt H, Acklin Y, Stanic B, Garcia M, et al. Diagnostic challenges and future perspectives in fracture-related infection. Injury. 2018;49:S83–90. Trampuz A, Zimmerli W. Diagnosis and treatment of infections associated with fracture-fixation devices. Injury 2006;37:S59–66. Rotter T, Kinsman L, James E, Machotta A, Gothe H, Willis J, et al. Clinical pathways: effects on professional practice, patient outcomes, length of stay and hospital costs. Cochrane Database Syst Rev 2010;(3):CD006632. Kim PH, Leopold SS. In brief: Gustilo-Anderson classification. [corrected]. Clin Orthop Relat Res 2012;470:3270–4. Noumi T, Yokoyama K, Ohtsuka H, Nakamura K, Itoman M. Intramedullary nailing for open fractures of the femoral shaft: evaluation of contributing factors on deep infection and nonunion using multivariate analysis. Injury 2005;36:1085–93. Pollak AN, Jones AL, Castillo RC, Bosse MJ, MacKenzie EJ; LEAP Study Group. The relationship between time to surgical debridement and incidence of infection after open high-energy lower extremity trauma. J Bone Joint Surg Am 2010;92:7–15. Hull PD, Johnson SC, Stephen DJ, Kreder HJ, Jenkinson RJ. Delayed debridement of severe open fractures is associated with a higher rate of deep infection. Bone Joint J 2014;96-B:379–84. Cross WW 3rd, Swiontkowski MF. Treatment principles in the management of open fractures. Indian J Orthop 2008;42:377–86. Swiontkowski MF, Engelberg R, Martin DP, Agel J. Short musculoskele-

tal function assessment questionnaire: validity, reliability, and responsiveness. J Bone Joint Surg Am 1999;81:1245–60. 12. Enninghorst N, McDougall D, Hunt JJ, Balogh ZJ. Open tibia fractures: timely debridement leaves injury severity as the only determinant of poor outcome. J Trauma 2011;70:352–7. 13. Harris AM, Althausen PL, Kellam J, Bosse MJ, Castillo R; Lower Extremity Assessment Project (LEAP) Study Group. Complications following limb-threatening lower extremity trauma. J Orthop Trauma 2009;23:1–6. 14. Metsemakers WJ, Kuehl R, Moriarty TF, Richards RG, Verhofstad MHJ, Borens O, et al. Infection after fracture fixation: Current surgical and microbiological concepts. Injury 2018;49:511–22. 15. Morgenstern M, Vallejo A, McNally MA, Moriarty TF, Ferguson JY, Nijs S, et al. The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. Bone Joint Res 2018;7:447–56. 16. Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: a new classification of type III open fractures. J Trauma 1984;24:742–6. 17. Jahangir N, Niazi N, Aljawadi A, Reid A, Wong J, Drampalos E, Pillai A. The use of adjuvant local antibiotic hydroxyapatite bio-composite in the management of open Gustilo Anderson type IIIB fractures. A prospective review. J Orthop 2019;16:278–82. 18. Wordsworth M, Lawton G, Nathwani D, Pearse M, Naique S, Dodds A, et al. Improving the care of patients with severe open fractures of the tibia: the effect of the introduction of Major Trauma Networks and national guidelines. Bone Joint J 2016;98-B:420–4.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Alt ve üst ekstremitenin açık kırıklarında eksternal fiksatör uygulanmış internal fiksasyona geçilen olgularda komplikasyonların değerlendirilmesi Dr. Mahmut Bilir,1 Dr. Sezgin Bahadır Tekin2 1 2

Adıyaman Üniversitesi Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Adıyaman Dr. Ersin Arslan Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, Gaziantep

AMAÇ: Açık kırıklar tüm kas-iskelet sistemi yaralanmaları arasında önemli bir mortalite ve morbidite nedenidir ve sosyal, ekonomik birçok problemi beraberinde getirir. Gerek uzun tedavi süreleri gerekse işe dönüşün gecikmesi ile oluşan maliyet, bu durumları daha komplike hale getirmiştir. Bu çalışmada alt ve üst ekstremite açık kırıklarında eksternal fiksatör uygulanmış internal fiksasyona geçilen olgularda görülebilen komplikasyonların geriye dönük olarak olarak değerlendirilmesi amaçlanmıştır. GEREÇ VE YÖNTEM: Çalışmaya 2007–2013 yılları arasında tedavi görmüş 49 hasta alındı. Bu hastaların 32’sine ilk yaralanmaları itibariyle kliniğimizde eksternal fiksatör uygulandı, geri kalan 17’si dış merkezde ilk tedavileri olan eksternal fiksatör uygulandıktan sonra kliniğimize başvurdular. Tüm hastaların yaralanma mekanizmaları, eksternal fiksatör ile takip periyodları, eksternal fiksatör sonrası debritman uygulanıp uygulanmadığı, eksternal fiksayondan internal fiksasyona geçerkenki süre, pin dibi enfeksiyonu, kaynama zamanı, geç kaynama, kaynamama, internal fiksasyon sırasında greft kullanımı, internal fiksasyon türü, reoperasyonu, osteomyelit varlığı ve takip zamanları kaydedildi. BULGULAR: Radius, humerus, tibia ve femur kırıkları için sonuçlar ayrı ayrı değerlendirildi. Kırk dokuz hasta içinde 39 erkek,10 kadın mevcuttu. ortalama takip zamanı tibia için 28.6 ay, femur için 34, humerus için 26.9, radius için 27 aydı. Kırk dokuz hastanın 34’ü alt ekstremite (25 tibia, 9 femur), 15’i üst ekstremte (11 humerus, 4 radius) yaralanmasıydı. Kırk dokuz hastanın 32’sinde pin dibi enfeksiyonu, 11 olguda nonunion, 11 olguda gecikmiş kaynama, iki hastada ise osteomyelit bulguları mevcuttu. TARTIŞMA: Açık kırıkları tedavi etmek daima zordur. Eksternal fiksasyon sonrası internal fiksasyona geçilen açık kırıklarda komplikasyonlara açıktır ve klinisyenlerin bu konunun bilincinde olup çıkabilecek sorunlara göre plan yapmaları gerekir. Anahtar sözcükler: Açık kırık; eksternal fiksator; internal fiksasyon. Ulus Travma Acil Cerrahi Derg 2020;26(6):865-869

doi: 10.14744/tjtes.2020.80236

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

869

ORIGIN A L A R T IC L E

Older patients with intraventricular hemorrhage are prone to infection after external ventricular drainage Soner Yaşar, M.D.,

Alparslan Kırık, M.D.

Department of Neurosurgery, University of Health Sciences Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: External ventricular drainage (EVD) is a life-saving and emergent procedure in neurosurgery. However, infection is the main problem in patients with EVD. The present study aims to analyze the infection rate of patients with EVD and to investigate the factors that contribute to infection and mortality rates. METHODS: The data of patients who underwent emergent EVD procedure between 2018 and 2019 were retrospectively analyzed in this study. The demographic features of the patients were recorded. The correlation between age, gender, indication and duration of EVD, and the infection and mortality rate were investigated. RESULTS: In this study, 47 patients underwent emergent EVD in two years. Thirty (63.83%) patients were male, and 17 were female with a mean age of 28.02 years. The mean duration of drainage was 6.2 days. Fifty-eight cerebrospinal fluid (CSF) samples were analyzed during the drainage period and CSF culture was positive in 14 (24.14%) samples. The most common microorganism was Staphylococcus epidermidis. The infection rate was high in older and male patients with duration longer than six days. Nine (19.15%) patients died during the treatment period and six of them had IVH. CONCLUSION: The duration of EVD should be shorter in patients older than 65 years with the diagnosis of intraventricular hemorrhage, which is mostly related to death. Keywords: Cerebrospinal fluid; external ventricular drainage; mortality; neurosurgery.

INTRODUCTION External ventricular drainage (EVD) systems are devices placed in cases of acute hydrocephalus or intraventricular hemorrhage to monitor intracranial pressure (ICP) and to drain the cerebrospinal fluid (CSF) or blood within the ventricle.[1] It is a basic and simple but emergent treatment method in patients with increased ICP which is a life-threatening condition.[1,2] Moreover, it plays a therapeutic role by allowing drainage of CSF or intraventricular blood. However, the main disadvantage of EVD is the risk of infection (ventriculitis or meningitis) arises due to this procedure. In the literature, the risk of infection has been reported between 0–45%.[2–4] The infection secondary to EVD may lead to significant morbidity or mortality if not it is managed properly.[5,6]

Today, the diagnostic criteria of infection are significant for treatment. The strongest diagnostic criterion is the CSF culture, which is obtained during the drainage. Another reliable diagnostic method is cell count within the CSF. The decrease in CSF glucose level and the increase in protein level are less reliable than the CSF culture or cell count, but should also be measured in the CSF.[6,7] However, it is not well documented the factors that contribute the infection rates in patients with EVD. Duration of EVD, primary disease-causing increased ICP, concomitant infection, type of surgical intervention, CSF fistula are defined as risk factors for infection during EVD.[6–9] Many factors have also been investigated previously to reduce the infection rate during the EVD. However, discussions on differ-

Cite this article as: Yaşar S, Kırık A. Older patients with intraventricular hemorrhage are prone to infection after external ventricular drainage. Ulus Travma Acil Cerrahi Derg 2020;26:870-874. Address for correspondence: Soner Yaşar, M.D. SBÜ Gülhane Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, Ankara, Turkey Tel: +90 312 - 304 53 44 E-mail: dr.soneryasar@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):870-874 DOI: 10.14744/tjtes.2020.06159 Submitted: 19.06.2020 Accepted: 16.07.2020 Online: 21.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

870

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Yaşar et al. Older patients with intraventricular hemorrhage are prone to infection after EVD

ent variables still continue. The duration of EVD is a matter of debate on ventriculostomy-related infections.[8–10]

(a)

(b)

In our study, the data of patients who underwent emergent EVD in the department of neurosurgery between 2018–2019 were examined retrospectively. Different factors were analyzed to investigate the infection and mortality rates in patients with EVD.

MATERIALS AND METHODS The ethical approval of this retrospective study was obtained from our institution. In this study, 47 patients underwent EVD (Argifix®, ArgiGroup, Ankara, Turkey) in the Department of Neurosurgery between January 2018 and December 2019 (Fig. 1).

Figure 1. Picture of an external ventricular drainage system. (a) Ventricular catheter (white arrow), small silicone fixation tab (yellow arrow) and trocar needle (red arrow) to allow catheter passage under the skin. (b) Drip chamber (white arrow) and collection bag (red arrow).

EVD Technique The patient was laid on the bed with slight head elevation in the supine position. Hair was removed, and the scalp was prepared in a sterile fashion. After installation of local anesthesia, a burr hole was placed at Kocher’s point or Frazier’s point based on the ventricular anatomy of the patient. The dura was coagulated and opened. Then, the ventricular catheter was inserted, aiming in a coronal plane toward the medial canthus of the ipsilateral eye and in the anteroposterior plane toward a point 1.5 cm anterior to the ipsilateral tragus, toward the ipsilateral Foramen of Monro. In cases of intraventricular hemorrhage, endoscopic ventricle irrigation was performed and the ventricle catheter was inserted under endoscopic visualization (Fig. 2). The length of the catheter was determined based on the anatomy and size of ventricles. Once the CSF flow was visualized, the catheter was fixed with suture. Then, it was tunneled through the skin away from the point of entry and connected to the drainage bag or reservoir. Periodical CSF samples were obtained from the reservoir for biochemical and microbiological analysis. CSF culture is a routine procedure in our department in patients with EVD. The data of patients were collected and analyzed. Age, gender, diagnosis, duration of EVD, CSF glucose and protein levels, results of CSF culture and the outcomes of the patients were retrospectively examined. SPSS 19.0 software was used for statistical analysis (SPSS Inc., Chicago, IL). Descriptive statistics, Spearman correlation and chi-square test were used for the analysis of the data. A p value ≤0.05 was accepted as an indicator of significance in all comparisons.

RESULTS A total of 47 patients underwent EVD over two years. Thirty (63.83%) patients were male and 17 were female with a mean age of 28.02 years (ranged between 0 and 88 years). Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Figure 2. Endoscopic view of EVD catheter within the ventricle (MB: Mamillary bodies, TS: Tuber cinereum, Cat: Catheter).

The mean duration of drainage was 6.2 days, ranged between three and nine days. The diagnosis of patients were hydrocephalus (n=22) (Fig. 3a), intraventricular hemorrhage (IVH) (n=13) (Fig. 3b), intraventricular tumor (n=7) (Fig. 3c), posterior fossa tumors (n=4) and traumatic brain injury (n=1) (Table 1). Fifty-eight CSF samples were obtained from 47 patients. CSF culture was positive in 14 (24.14%) of 58 samples. Staphylococcus epidermidis (n=4), Enterococcus faecium (n=2), Klebsiella pneumoniae (n=2), Staphylococcus haemolyticus (n=2), Acinetobacter baumannii (n=2), Staphylococcus hominis (n=1) and Mycobacterium spp (n=1) were identified in the culture of 58 CSF samples. The mean CSF glucose was 29.78 mg/dl (ranged between 1 and 63.3 mg/dl) and the mean CSF protein level was 428.31 mg/dl (ranged between 134 and 707 mg/dl) in patients with positive CSF culture. Infection was more common in male patients, but this is not statistically significant (p>0.05). The duration of EVD is statistically significantly correlated with the infection rate (p<0.05). In addition, the infection was more frequent in patients older than 871

Yaşar et al. Older patients with intraventricular hemorrhage are prone to infection after EVD

(a)

(b)

(c)

Figure 3. (a) Axial CT scan of a 60-years old male patient with hydrocephalus. The catheter was inserted through Frazier’s point. (b) Coronal CT scan of a 64-years old male patient with intraventricular hemorrhage. The EVD catheter is passing through the brain tissue and reaching to the lateral ventricle. (c) Sagittal CT scan of a 32-years old female patient with an intraventricular tumor. The EVD catheter was in the lateral ventricle in front of the tumor.

65 years old and this is also statistically significant (p<0.05). Nine (19.15%) of 47 patients died during the follow-up period. Among them, microorganism (Mycobacterium spp) was isolated in only one patient and the pre-EVD diagnosis was IVH in six patients. Univariate regression analysis demonstrated that the risk of infection is significantly increased in patients older than 65 years old (p<0.05).

DISCUSSION EVD is a basic and simple method of treatment in patients with increased ICP. EVD is performed in medical practice since the second half of the 18th century. It is also used to drain blood or infected CSF in patients with IVH or infection. The main disadvantage of EVD is the risk of life-threatening ventriculitis or meningitis due to this application. Champey et al.[9] performed a retrospective study in 462 patients with EVD and they suggested an EVD care bundle, which can include routine daily CSF sampling, for prevention of EVD-related infection. Sam et al.[10] reported an infection rate of 6.3% in 796 patients with EVD and they found that Acinetobacter baumannii was the most common organism causing ventriculostomy-related infection. In our series, CSF infection was detected in 14 of 47 patients and one of them died after the treatment in whom the diagnosis was intraventricular hemorrhage. Staphylococcus epidermidis was mostly isolated

microorganism in our series. The CSF glucose level should be 40–80 mg/dl and the CSF protein level should be 15–60 mg/dl in normal healthy individuals. However, in our series, the mean CSF glucose level was 29.78 mg/dl and the mean CSF protein level was 428.31 mg/dl among patients with CSF infection. The CSF protein level was significantly high in patients with infection and the glucose level was below the normal CSF glucose level. Hydrocephalus is the most common indication of EVD. Hydrocephalus may develop due to intracranial tumors or hemorrhages by blocking the CSF pathways or impairing CSF absorption.[11–13] This increases ICP and poses a life-threatening condition to the patient. EVD placement is an emergent but life-saving procedure in hydrocephalus patients whose clinical condition is rapidly deteriorating and unconscious,[14] especially in hydrocephalus patients with shunt dysfunction, this procedure decreases rapidly the ICP and prevent the brain herniation. Emergent EVD is also placed in intraventricular hemorrhages (IVH) that have occurred for different reasons besides hydrocephalus. Subarachnoid hemorrhages are the main causes of IVH, followed by intraventricular tumors or ventricular injuries secondary to severe head traumas. Emergent evacuation of the intraventricular blood is required by the placement of EVD. Song et al.[11] compared the EVD and

Table 1. The demographic features and laboratory results of 47 patients who underwent EVD Indication of EVD

Number of patients

Mean age (years)

Male/ Female

Mean CSF glucose (mg/dL)

Mean CSF protein (mg/dL)

5 14/8 12.35

Positive CSF culture

Death

Hydrocephalus

524.6

13 1

Intraventricular hemorrhage

65.75

9/4

40.24

367.43

Intraventricular tumor

42.26

3/4

45.56

100.8

Posterior fossa tumor

34.43

3/1

70.12

66.58

Traumatic brain injury

1/0

54.9

147.7

CSF: Cerebrospinal fluid; EVD: External ventricular drainage.

872

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Yaşar et al. Older patients with intraventricular hemorrhage are prone to infection after EVD

endoscopic evacuation in patients with IVH and they found that endoscopic hematoma evacuation has an advantage of a higher hematoma clearance rate, fewer complications and better outcomes in severe IVH. Basaldella et al.[15] pointed out that endoscopic blood aspiration reduces shunt dependency in patients with IVH. In our series, 13 (27.66%) of 47 patients underwent EVD for IVH and six (66.66%) of them died despite the treatment. The mean age of these patients was 65.75 years and all of them had associated co-morbidities. Our findings revealed that patients older than 65 years were more prone to infection when compared with younger patients. In addition, the infection was more common in male patients, but this was not statistically significant. EVD is also widely used to lower ICP after traumatic brain injuries (TBI).[16] Craniocerebral gunshot wounds may increase ICP and conventional methods fail to treat intracranial hypertension.[16–19] In those times, emergent EVD may be a life-saving procedure for the patient. Bhargava et al.[20] reported their study on the efficacy of EVD on the management of increased ICP in 139 patients with TBI refractory to conventional medical treatment. EVD was inserted in 16 patients and they found that patients treated with EVD had a lower risk of needing definitive treatment for ICP control. Chau et al.[21] emphasized the significance of EVD in the management of TBI. They suggested that this procedure can improve brain perfusion and mitigate the risk of exacerbating the secondary cerebral injury, as well as reduce the probability of brain herniation in TBI patients. In our series, one of the 47 patients had a traumatic brain injury and underwent EVD for seven days. This patient was discharged after a successful treatment period. Silicone catheters are generally used in EVD systems and it is claimed that bacterial colonization is less in these catheters.[22] However, it has been suggested that polyurethane catheters can also be used for CSF drainage.[23] We should note that antibiotics or silver-impregnated catheters have also been shown to be effective in preventing infection.[23–26] Meanwhile, Nilsson et al.[27] reported that silver-coated EVD cannot reduce the use of antibiotics or provide shorter hospital stay in cases of ventriculitis. Studies on the development of EVD catheters are still ongoing. In our series, we used silicone catheters in all patients and not used any antibiotic or silver-impregnated catheter. However, our infection rate was compatible with the series of antimicrobial catheters. This is probably due to the lost antimicrobial features of catheters after a short period following EVD insertion. The limitations of our study are the retrospective nature and low patient population.

Conclusion The duration of EVD should be shorter than six days in patients older than 65 years to prevent the infection. IVH is related to high mortality. More clinical studies in larger populaUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

tions help us to reveal the correlation between the mortality and EVD procedure. Ethics Committee Approval: Health sciences university non-interventional research ethics Committee granted approval for this study (date: 28.01.2020, number: 464189262020-32). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.Y.; Design: S.Y.; Supervision: A.K.; Materials: S.Y.; Data: S.Y.; Analysis: S.Y., A.K.; Literature search: S.Y.; Writing: S.Y.; Critical revision: A.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Muralidharan R. External ventricular drains: Management and complications. Surg Neurol Int 2015;6:S271−4. 2. Cinibulak Z, Aschoff A, Apedjinou A, Kaminsky J, Trost HA, Krauss JK. Current practice of external ventricular drainage: a survey among neurosurgical departments in Germany. Acta Neurochir (Wien) 2016;158:847−53. 3. Fried HI, Nathan BR, Rowe AS, Zabramski JM, Andaluz N, Bhimraj A, et al. The Insertion and Management of External Ventricular Drains: An Evidence-Based Consensus Statement: A Statement for Healthcare Professionals from the Neurocritical Care Society. Neurocrit Care 2016;24:61−81. 4. Yuen J, Selbi W, Muquit S, Berei T. Complication rates of external ventricular drain insertion by surgeons of different experience. Ann R Coll Surg Engl 2018;100:221−5. 5. Dey M, Jaffe J, Stadnik A, Awad IA. External ventricular drainage for intraventricular hemorrhage. Curr Neurol Neurosci Rep 2012;12:24−33. 6. Gündüz B, Ekinci B, Ucar B, Toplamaoglu H. Factors that increase the risk of infection during external ventricular catheterization. Türk Nöroşir Derg 2006;16:105−9. 7. Afifi AM, Abdullah JM, Siregar JA, Idris Z. A Retrospective Study on the First Cerebrospinal Fluid Taken from External Ventricular Drainage Insertion in Meningitis Patients with Hydrocephalus. Malays J Med Sci 2019;26:64−73. 8. Baysallar M, Izci Y, Kilic A, Avci IY, Senses Z, Doganci L. A case of ventricular drainage infection with a rare pathogen in cerebrospinal fluid: vancomycin-resistant Enterococcus faecium. Microb Drug Resist 2006;12:59−62. 9. Champey J, Mourey C, Francony G, Pavese P, Gay E, Gergele L, et al. Strategies to reduce external ventricular drain-related infections: a multicenter retrospective study. J Neurosurg 2019;130:2034−9. 10. Sam JE, Lim CL, Sharda P, Wahab NA. The organisms and factors affecting outcomes of external ventricular drainage catheter-related ventriculitis: A Penang experience. Asian J Neurosurg 2018;13:250−7. 11. Song P, Duan FL, Cai Q, Wu JL, Chen XB, Wang Y, et al. Endoscopic Surgery versus External Ventricular Drainage Surgery for Severe Intraventricular Hemorrhage. Curr Med Sci 2018;38:880−7. 12. Seçer HI, Düz B, Izci Y, Tehli O, Solmaz I, Gönül E. Tumors of the lateral ventricle: the factors that affected the preference of the surgical approach in 46 patiens. Turk Neurosurg 2008;18:345−55. 13. Nakashima T, Iijima K, Muraoka S, Koketsu N. Acute hydrocephalus

873

Yaşar et al. Older patients with intraventricular hemorrhage are prone to infection after EVD requiring external ventricular drainage following perimesencephalic nonaneurysmal subarachnoid hemorrhage in a pediatric patient: Case reportand review of the literature. World Neurosurg 2019;129:283−6. 14. Hepburn-Smith M, Dynkevich I, Spektor M, Lord A, Czeisler B, Lewis A. Establishment of an External Ventricular Drain Best Practice Guideline: The Quest for a Comprehensive, Universal Standard for External Ventricular Drain Care. J Neurosci Nurs 2016;48:54−65. 15. Basaldella L, Marton E, Fiorindi A, Scarpa B, Badreddine H, Longatti P. External ventricular drainage alone versus endoscopic surgery for severe intraventricular hemorrhage: a comparative retrospective analysis on outcome and shunt dependency. Neurosurg Focus 2012;32:E4. 16. Izci Y, Kayali H, Daneyemez M, Koksel T, Cerrahoglu K. The clinical, radiological and surgical characteristics of supratentorial penetrating craniocerebral injuries: a retrospective clinical study. Tohoku J Exp Med 2003;201:39−46. 17. Izci Y, Kayali H, Daneyemez M, Koksel T. Comparison of clinical outcomes between anteroposterior and lateral penetrating craniocerebral gunshot wounds. Emerg Med J 2005;22:409−10. 18. Erdogan E, Izci Y, Gonul E, Timurkaynak E. Ventricular injury following cranial gunshot wounds: clinical study. Mil Med 2004;169:691−5. 19. Solmaz I, Kural C, Temiz C, Seçer HI, Düz B, Gönül E, et al. Traumatic brain injury due to gunshot wounds: a single institution’s experience with 442 consecutive patients. Turk Neurosurg 2009;19:216−23. 20. Bhargava D, Alalade A, Ellamushi H, Yeh J, Hunter R. Mitigating effects of external ventricular drain usage in the management of severe head in-

jury. Acta Neurochir (Wien) 2013; 155:2129−32. 21. Chau CYC, Craven CL, Rubiano AM, Adams H, Tülü S, Czosnyka M, et al. The Evolution of the Role of External Ventricular Drainage in Traumatic Brain Injury. J Clin Med 2019;8:1422. 22. Verma A, Bhani D, Tomar V, Bachhiwal R, Yadav S. Differences in Bacterial Colonization and Biofilm Formation Property of Uropathogens between the Two most Commonly used Indwelling Urinary Catheters. J Clin Diagn Res 2016;10:PC01−3. 23. Izci Y, Secer H, Akay C, Gonul E. Initial experience with silver-impregnated polyurethane ventricular catheter for shunting of cerebrospinal fluid in patients with infected hydrocephalus. Neurol Res 2009;31:234−7. 24. Secer HI, Kural C, Kaplan M, Kilic A, Duz B, Gonul E, et al. Comparison of the efficacies of antibiotic-impregnated and silver-impregnated ventricular catheters on the prevention of infections. An in vitro laboratory study. Pediatr Neurosurg 2008;44:444−7. 25. Lajcak M, Heidecke V, Haude KH, Rainov NG. Infection rates of external ventricular drains are reduced by the use of silver-impregnated catheters. Acta Neurochir (Wien) 2013;155:875−81. 26. Lemcke J, Depner F, Meier U. The impact of silver nanoparticle-coated and antibiotic-impregnated external ventricular drainage catheters on the risk of infections: a clinical comparison of 95 patients. Acta Neurochir Suppl 2012;114:347−50. 27. Nilsson A, Uvelius E, Cederberg D, Kronvall E. Silver-Coated Ventriculostomy Catheters Do Not Reduce Rates of Clinically Diagnosed Ventriculitis. World Neurosurg 2018;117:e411−6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yaşlı ve intraventriküler kanaması olan hastalar eksternal ventrikül drenajı sonrası enfeksiyona daha yatkındır Dr. Soner Yaşar, Dr. Alparslan Kırık Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, Ankara

AMAÇ: Eksternal ventrikül drenajı (EVD) nöroşirürjide hayat kurtarıcı ve acil uygulanan bir girişimdir. Ancak enfeksiyon, EVD uygulanan hastalarda temel sorundur. Bu çalışmanın amacı, EVD’li hastaların enfeksiyon oranlarını analiz etmek ve enfeksiyon ve mortalite oranlarına katkıda bulunan faktörleri belirlemektir. GEREÇ VE YÖNTEM: 2018–2019 yılları arasında acil EVD prosedürü uygulanan hastaların verileri geriye dönük olarak incelendi. Hastaların demografik özellikleri kaydedildi. Yaş, cinsiyet, EVD endikasyonu ve süresi ile enfeksiyon ve mortalite oranı arasındaki ilişki araştırıldı. BULGULAR: Toplam 47 hastaya iki yıllık dönemde acil EVD uygulandı. Otuz (%63.83) hasta erkek, 17’si kadın olup ortalama yaş 28.02 idi. Ortalama drenaj süresi 6.2 gündü. Drenaj döneminde 58 beyin omurilik sıvısı (BOS) örneği analiz edildi ve 14 (%24.14) örnekte BOS kültürü pozitif bulundu. En yaygın mikroorganizma Staphylococcus epidermidis idi. Altı günden daha uzun süren yaşlı ve erkek hastalarda enfeksiyon oranı yüksekti. Dokuz (%19.15) hasta tedavi süresince öldü ve altısında intraventriküler kanama vardı. TARTIŞMA: Altmış beş yaş üstü ve intarventriküler kanaması olan hastalarda EVD süresi daha kısa olmalıdır. Bu hasta grubunda mortalite daha yüksektir. Anahtar sözcükler: Beyin-omurilik sıvısı; eksternal ventrikül drenajı; mortalite; nöroşirürji. Ulus Travma Acil Cerrahi Derg 2020;26(6):870-874

874

doi: 10.14744/tjtes.2020.06159

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

Does a selective surgical approach to malignant bowel obstruction help in palliative care patients? Ahmet Akbaş, M.D.,1 Hüseyin Bakır, M.D.,2

Emin Daldal, M.D.,2 Fatih Daşıran, M.D.,2 Hasan Dagmura, M.D.,2 İsmail Okan, M.D.2

Department of General Surgery, University of Health Sciences, Bağcılar Training and Research Hospital, İstanbul-Turkey

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

ABSTRACT BACKGROUND: Malignant bowel obstruction (MBO) is a condition secondary to intra-abdominal metastatic spread of advanced-stage tumors. There is no consensus for the treatment approach of MBO. This study aims to present the results of medical treatment and palliative surgery in patients diagnosed with MBO. METHODS: The patients who were treated for advanced-stage tumors between 2010 and 2017 and for whom consultation was requested from the surgical clinic for MBO symptoms were identified. A selective approach together with palliative care for the indication of surgery was instituted. The patients with surgical treatment and medical treatment were compared concerning survival, oral food intake and symptom relief. RESULTS: Seventy-six patients (30 female, 46 male) aged 60.5±12.8 years (range: 27–88) were included in this study. Forty-eight of the patients (64.9%) underwent surgical treatment, while 28 (35.1%) had medical treatment. Although the patients with surgery had longer duration of stay in the hospital (median 16 days vs. 4 days) (p<0.001) and higher complication rates (27.1% vs. 3.5%) compared to medically treated patients; the restoring oral food intake was better (97.9% vs. 78.6%) (p=0.005) and the survival was longer (105 days vs. 43 days). CONCLUSION: This study revealed that surgical treatment resulted in better outcomes for life quality parameters in highly selected patients with malignant bowel obstruction evaluated by multidisciplinary team, including palliative care. Keywords: Malignant bowel obstruction; palliative surgery; tumor; Ileus.

INTRODUCTION Malignant bowel obstruction (MBO) is a devastating condition at the end of life threatening the patients with advanced-stage of tumors originated from or metastatic to abdominal cavity. The most common etiological causes are ovarian and colon cancers,[1,2] while the incidence of extra-abdominal tumors due to peritoneal metastasis is rather low.[3,4] Patients have a functional or mechanical obstruction in the GIS that interferes with physiological passage and digestion. These patients experience many adverse events, such as nausea, vomiting, distention and lack of oral food intake with an average life expectancy of four months.[5]

Although it is uncommon, the management of these patients is quite challenging. Usually, conservative methods like medication (i.e., antiemetics, somatostatin and steroids) and stenting prevails the initial treatment; they often fail in a short term. Palliative surgical treatment is another important option for maintaining GIS integrity. Although it is a treatment of choice in select patients, which may provide prompt symptom control and improvement of quality of life, the complication rate is high.[6] Unlike the patients receiving conservative measurements that have a shorter life expectancy, diminished quality of life due to rapid progression of symptoms, compromisation of oral food intake and rapid deterioration of general health condition, selected patients who were appropriate to

Cite this article as: Akbaş A, Daldal E, Daşıran F, Bakır H, Dagmura H, Okan İ. Does a selective surgical approach to malignant bowel obstruction help in palliative care patients?. Ulus Travma Acil Cerrahi Derg 2020;26:875-882. Address for correspondence: Ahmet Akbaş, M.D. Kale Ardı Mahallesi, Muhittinfusunoğlu Caddesi, 60000 Tokat, Turkey Tel: +90 256 - 212 95 00 / 3563 E-mail: draakbas@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):875-882 DOI: 10.14744/tjtes.2020.90250 Submitted: 31.05.2020 Accepted: 17.10.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

875

Akbaş et al. Does a selective surgical approach to MBO help in palliative care patients?

undergo palliative surgical treatment have better outcomes for these parameters. In general, six-month life expectancy is approximately 50% in patients who undergo surgical treatment, but this rate is only approximately 8% in patients who undergo medical treatment.[7,8] Therefore, a good evaluation of these patients who have a short life expectancy and careful use of the surgical option could help physicians, patients and their relatives during the process. Despite modern diagnostic and therapeutic approaches, the long-term prognosis of MBO remains poor. Many departments dealing with such patients make their decisions depending on their available resources, experiences and patient expectations. Although the burden to patient/family, physicians and healthcare system and the discouraging results with treatments overall necessitates more studies, it is very difficult to establish a clear protocol for the management of MBO due to the inherent features of the disease like scarcity of patients, progressive nature of the disease and so on. The present study aims to evaluate the treatment approaches in patients with MBO in the light of the literature and to compare the surgical and medical treatment options for various patient outcomes.

MATERIALS AND METHODS After approval of the institutional review board (IRB) of Tokat Gaziosmanpaşa University, Faculty of Medicine (IRB number: 17-KAEK-191), the patients who were admitted to general surgery or surgical oncology department with malignant bowel obstruction during 2010 and 2017 were retrieved from an electronic data file with ICD-10 code of K56. We also reviewed the consultation requests with the keywords of “obstruction, ileus”. from different clinical (e.g., internal medicine, oncology, palliative care, radiation oncology, emergency and obstetrics and gynecology) departments to the general surgery department and retrieved the patients with malignant bowel obstruction. Patients, consultation notes of general surgery clinic, consultations requests from other clinics were reviewed and re-examined and doubly-checked by scanning “obstruction and ileus” words in hospital database by one of the authors (AA). Patients who were operated for curative purposes with MBO diagnosis but whose records were not available in the follow-up period and those patients referred to our clinic but did not have obstruction symptoms were excluded from this study. Our university hospital is a tertiary referral center located in Northeastern Anatolia, serving around 600.000 inhabitants, having the only in the vicinity and fully-functional oncology facility, including surgical, medical, radiation oncology and palliative care units. The patients with obstruction from the emergency department, outpatient surgical oncology department or from consultations were admitted to the ward. The routine first-line workout for blood chemistry and abdominal plain radiography was studied. Medical treatment before surgery for MBO is based on NPO, 876

parenteral hydration, nasogastric aspiration, and the use of octreotide or analgesics and antiemetic drugs. The aims of these measures are to control the symptoms, reestablish the hydroelectrolytic balance, favor spontaneous resolution, and gain the time necessary to establish a diagnostic process to facilitate individualized surgical decisions. With these measures, adequate control of the symptoms is achieved in 80% of cases if NPO and nasogastric aspiration are maintained. It is reasonable to assume that nasogastric aspiration at the onset of the obstruction may favor spontaneous resolution since it drastically reduces the endoluminal gastric pressure. However, long-term nasogastric aspiration is uncomfortable for the patient and has intense secondary effects (e.g., esophagitis, gastroesophageal reflux, nasal erosions and bronchoaspiration). Once the patient is stabilized, an abdominal computerized tomography and endoscopy were obtained. The value of operative intervention for bowel obstruction in cancer patients has even been claimed to be limited to the presence of a benign obstruction cause, but not to carcinomatosis. Unfortunately, complete MBOs do not resolve after exclusively nonoperative treatment, and if the ability to take solid food is considered desirable, an operation seems to remain the only possible therapeutic option. The decision was based mainly on the patients’ general condition, including nutritional status, comorbidities, performance status and CT findings. Some CT findings have helped to exclude the patients from surgery since they would not benefit much. The main finding in CT was the diffuse involvement of small intestinal mesenteric root causing condensation of the mesentery and gathered all intestines in the midline rendering them hard to move which was called Bluto. The diffuse involvement of intestine and mesentery with peritonitis carcinomatosa and massive ascites was the relative contraindications for the surgery. After the imaging, patients were consulted for a thorough palliative care evaluation. It consisted of a holistic evaluation of the patient and the discussion with the patient and family, which included a realistic description of the situation and revealed the expectations, goals and treatment preferences of the patients and family. After a discussion in the surgical grand round, a treatment preference was chosen for the patient.

MBO Criteria The diagnosis of MBO was made based on both the signs of symptoms of obstruction (intestinal obstruction findings, the development of obstruction through the distal part of the pylorus) and the presence of malignancy (peritoneal metastasis of primary intra-abdominal or extra-abdominal cancers with peritoneal involvement and the absence of reasonable possibilities for a cure).

Demographic and Clinical Variables The patients were grouped into two: The first group included the patients receiving medical treatment or care of the obstruction; the second group included the patients who Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

AkbaĹ&#x; et al. Does a selective surgical approach to MBO help in palliative care patients?

underwent the surgical treatment for the purpose of obstruction. Age, the gender of the patients, primary diagnosis, clinical symptoms, CT findings (presence of ascites, peritoneal involvement, visceral organ metastasis, obstruction level), presence of surgery, received adjuvant chemotherapy or radiotherapy, food toleration at admission, post-treatment removal of a nasogastric tube (NGT), length of hospitalization, development of a complication, duration of time through the discharge and length of survival of the patients were retrieved from electronic files of the patients and recorded and compared between these two groups.

Quantitative data were expressed as median and interquartile range. Mann-Whitney U test and Kruskal Wallis ANOVA were used to compare the continuous non-normal variables between the groups. Independent samples t-test or one-way analysis of variance was used to compare the normally distributed variables between the groups. Kaplan Meier method was used for determining survival probabilities and survival curves. Spearman correlation coefficient was used for bivariate correlation of variables. A p-value <0.05 was considered significant. Statistical analyses were performed using SPSS 19 (IBM SPSS Statistics 19, SPSS Inc., an IBM Co., Somers, NY).

RESULTS

Statistical Analyses Descriptive analyses were performed to provide information on the general characteristics of the study population.

In this study, 107 patients were included at the outset. A detailed analysis revealed that thirty-one patients were either

Table 1. Distribution of qualitative variables

NGT inserted when first arrived

Gender Female

30 39.5

Yes

45 59.2

Male

46 60.5

31 40.8

Removal of NGT after treatment

Obstruction level

Small intestine

57.9

Yes

69 90.8

Large intestine

30.3

Gastric-outlet

9 11.8

9.2

Treatment Surgery

48 63.2

Yes

46 60.5

Medical

28 36.8

30 39.5

Oral food intake after treatment

Ascites in computed tomography

Visceral organ involvement in computed

Solid food

76.3

Liquid food

13.2

Yes

49 64.5

No oral intake

10.5

27 35.5

Discharge status

tomography

Peritoneal involvement in computed tomography

Exitus

16 20.0

Discharge

60 80.0

Yes

36 47.4

Readmission due to the same complaint

40 52.6

Yes

33 43.4

43 56.6

Primary tumor operated Yes

43 56.6

Relief of symptoms after treatment

33 43.4

Yes

68 89.5

8 10.5

Receiving adjuvant chemotherapy Yes

53 69.7

23 30.3

Receiving chemotherapy in the last six weeks

Etiological cause

Colo-rectal Cancer

44.7

Gastric cancer

34.2

Yes

18 23.7

Small intestine cancer

5.2

58 76.3

Pancreas cancer

5.2

Ovarian cancer

3.9

Yes

22 28.9

Breast cancer

3.9

54 71.1

Renal cell cancer

2.6

Food tolerance at diagnosis

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

877

Akbaş et al. Does a selective surgical approach to MBO help in palliative care patients?

did not meet the MBO criteria or they lacked the necessary information in the files. Thus, this study included a final of 76 patients with MBO who were followed-up in our hospital. The mean age of the patients was 60.5±12.8 years (ranged 27–88 years) with predominantly male (46 male (60.5%)). Table 1 summarizes the demographic, clinical and treatment characteristics of this study. The mean age of the patients who underwent surgical treatment was 59.58±13.68 years, and the mean age of the patients who were treated with medical treatment was 62.21±10.8 years. Forty-eight patients (64.9%) underwent surgical treatment, while 28 (35.1%) patients had medical treatment. A comparison of patients treat-

ed with surgery and those treated with medical treatment is summarized in Table 2. In patients who underwent surgical treatment, the duration of hospital stay was longer (median 16 days [10.0–24.5 days] vs. four days [2.0–10.5 days], p<0.001) and the complication rate was higher (27.1% vs. 3.5%; p=0.003) compared to the medically treated patients. However, these patients had better outcomes, such as higher percentage of postoperative symptoms relief (95.8% vs. 78.6%; p=0.018), removal of NGT (97.9% vs. 78.6% ; p=0.005), restoring oral food intake (97.9% vs. 78.6%; p=0.005) and lower hospital readmissions, due to

Table 2. Quantitative variables in patient groups who underwent surgery and who had medical treatment (Mann-Whitney U test and Chi-square test were used) Variables

Applied treatment

Medical

p Surgery

Mean±SD or Median [IQR] or n (%)

Number (n)

28 (35.1)

48 (64.9)

Age (years)

62.21±10.8

59.58±13.68

0.387 0.645

Gender

Female

12 (42.9)

18 (37.5)

Male

16 (57.1)

30 (62.5)

Gastric outlet

2 (7.1)

7 (14.6)

Small intestine

22 (78.6)

22 (45.8)

Large intestine

4 (14.3)

19 (39.6)

Ascites in CT

23 (82.1)

23 (47.9)

0.003

Peritoneal involvement in CT

20 (71.4)

16 (33.3)

0.001

Visceral organ involvement in CT

22 (78.6)

27 (56.3)

0.049

Primary tumor operated

19 (67.9)

24 (50.0)

0.130

Receiving adjuvant chemotherapy

21 (75.0)

32 (66.7)

0.446

Receiving chemotherapy in the last six weeks

10 (35.7)

8 (16.7)

0.060

No food tolerance at diagnosis

14 (25.9)

40 (74.1)

0.002 0.005

Obstruction level

0.020

Oral food intake after treatment

Solid food intake

16 (57.1)

42 (87.5)

Liquid food intake

6 (21.4)

5 (10.4)

No oral intake

6 (21.4)

1 (2.1)

NGT inserted when first arrived

11 (39.3)

34 (70.8)

0.007

Removal of NGT after treatment

22 (78.6)

47 (97.9)

0.005

Relief of symptoms after treatment

22 (78.6)

46 (95.8)

0.018

Total length of hospital stay (days)

4 [2.0–10.5]

16 [10.0–24.5]

<0.001

1 (3.5)

13 (27.1)

0.003

Complication development Discharge from hospital

21 (75)

39 (83.0)

0.403

Readmission due to the same complaint

17 (60.7)

16 (33.3)

0.020

Length of survival after treatment (days)

43 [27–182.5]

105 [38–360]

0.035

NGT: Nasogastric tube; CT: Computed tomography; SD: Standard deviation.

878

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Akbaş et al. Does a selective surgical approach to MBO help in palliative care patients?

(a)

Treatment

1.0

Surgical Medical Surgical-censored Medical-censored

0.8

0.6

Cum Survival

(b)

Survival Functions

0.4

0.2

0.0

0.0 .00

20.00

40.00

60.00

80.00

100.00

120.00

Total length of hospital stay (days)

200

400

600

800

1000

1200

1400

Surgery after the extended time

Figure 1. (a) Total duration of hospital stays of the patients who underwent surgery and who had medical treatment. (b) Length of survival in patients who underwent surgery and who had medical treatment.

the same complaints (33.3% vs. 60.7%; p=0.020), and longer survival after treatment (105 days [38–360 days] vs. 43 days [27–182.5 days]; p=0.035) (Table 2 and Fig. 1).

DISCUSSION This retrospective study evaluated the effectiveness of the surgical intervention in highly selected MBO patients. Based on CT findings, patients’ medical conditions and palliative care consultation both with patient and the family caregivers, they were triaged either to medical treatment or surgical intervention. Our study showed that the surgical intervention was better at controlling in the symptoms which negatively affected the quality of life, such as nausea, vomiting and distension. The palliative surgery has also been associated with removal of NGT and restoring better oral food intake. Additionally, the readmission rate due to similar complaints was lower and survival after surgery was longer in this patient group. However, the patients who underwent palliative surgery had a longer hospital stay and higher complication rates. In MBO patients of advanced-stage cancer, multidimensional evaluation of the patients including the clinical findings, expected lifespan, expectations, hopes and realities should be promptly instituted through a multidisciplinary approach. Although the surgical treatment is a good option in benign intestinal obstruction cases, it may not be as satisfactory in advanced-stage cancer patients. Planning of the treatment by evaluating these patients with a multidisciplinary approach (e.g., clinical findings, CT images, presence of complete/incomplete obstruction, cachexia, comorbidity, multiple segment involvement, massive ascites and diffuse Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

peritoneal involvement) increases the success of the treatment applied.[9] MBO develops in 3–15% of the advanced-stage cancer patients, and the commonest two cancers are ovary (20-50%) and colon (10–29%).[10,11] During the follow-up periods of primary intraabdominal cancers, MBO develops in 25–40% of colon cancers, 16–29% of ovarian cancers, 6–19% of gastric cancers, 3–13% of pancreatic cancers, 3-10% of bladder cancers and 3–11% of endometrial cancers in decreasing orders. [10,12] MBO secondary to peritoneal metastasis of extra-abdominal tumors is relatively rare and most commonly seen in breast cancers (2-3%) and malignant melanomas (3%).[13,10] On the contrary, our study consisted of MBO cases mostly due to gastrointestinal system cancers, being ovarian cancer only about 4% (Table 1). The discrepancy could be due to the presence of a surgical oncology unit in our hospital, dealing mostly with gastrointestinal cancers and less gynecological cancers. Although the average age in our patients was about the same as the earlier reports (61 vs. 60.5), the male patients dominated different from the literature.[14,10] A putative explanation for this discrepancy could lie in our distinctive composition of tumor origin. Our study group mainly composed of gastric cancers of which males were readily affected than women. The same distribution also affected the time between the diagnoses of primary cancer and MBO. While the mean time between the diagnosis of primary cancer and the development of MBO in the literature was 14 months, our patients experienced an earlier diagnosis as 9.1 months. We speculated that our patients had gastric cancers diagnosed at 879

Akbaş et al. Does a selective surgical approach to MBO help in palliative care patients?

advanced stages, and their poor prognosis played important role in the earlier presentation of the patients with MBO. MBO constitutes more than 40% of the palliative consultations requested from the surgery department in advanced cancer patients.[9] Nausea, vomiting, distension and oral food intake disorder frequently seen in MBO have a negative effect on the life quality of advanced-stage cancer patients and individuals in their immediate vicinity. Unfortunately, there is still no standard treatment protocol for these patients. Each clinic has its approach depending on their own experiences. This is a challenging process for patients and physicians concerning treatment selection and follow-ups. Approximately 30% morbidity and 10% mortality was reported in palliative surgery performed due to nausea, vomiting, oral food intake disorder and cachexia complaints of these patients with a short life expectancy.[12,15] Therefore, the necessity of palliative surgery in these patients should be thoroughly evaluated, and the opinions and expectations of patients and their relatives should be taken into consideration when choosing medical or surgical treatment. The aim of the palliative treatment (medical or surgical treatment) in patients with MBO is to prevent vomiting, removal of NGT and, if possible, improve life quality by ensuring oral food intake. In these patients, the severity of complaints, such as nausea, vomiting, abdominal distension may vary depending upon complete or incomplete obstruction. Nausea can be seen in 100% of MBO cases, while vomiting is observed in 87–100%, colic abdominal pain in 72–80% and distension in 56–90%.[7,10] In MBO patients, who have medical treatment, complaints, such as nausea and vomiting spontaneously improved by 36% (31–42%). However, 60% of the patients experienced the recurrence of the symptoms over a short time and were readmitted to the hospitals.[14,16] In patients who underwent palliative surgery, these symptoms are less likely to recur and the patient’s life quality is better. [17] We have shown that oral food intolerance decreased from 74.1% to 2.1% in patients who underwent palliative surgical treatment, while this rate decreased from 25.9% to 21.4% in inoperable MBO patients receiving medical treatment. In addition, it was observed that palliative surgery patients benefited more due to the relief of the symptoms, which affected the life quality adversely, such as nausea and vomiting, due to the removal of NGT and restored oral food intake. The patients who underwent palliative surgery had significantly less hospital readmission due to similar symptoms, and their oral food intake was better (Table 2). The aim of palliative surgical treatment should be to relieve the complaints of patients, such as nausea, vomiting, distension and to restore oral food intake if possible. For this purpose, findings, such as the presence of diffuse peritoneal involvement, presence of malignant ascites, the involvement of multiple segments, palpable metastatic mass in the abdomen and cachexia, should be taken into consideration in the decision-making process. In the literature, different outcome rates have been reported in the palliative surgical treatment 880

of MBO. In general, 30 days mortality rate is 9–40%, while the postoperative morbidity rate is 9–90%, and the rate of re-obstruction is 39–57%, while the average survival time varies from two to 12 months.[1,10,18] Age, advanced-stage of the disease, hypoalbuminemia due to the nutritional deficiency, cachexia, presence of electrolyte imbalance, presence of malignant ascites, previous radiotherapy application to pelvic region due to the primary tumor, and general deterioration in patient’s conditions are among the poor prognostic factors in surgical treatment.[1,18,19] Therefore, it is important to support the patients with parenteral treatment, to use antiemetic drugs for nausea and vomiting, to correct electrolyte imbalance, to administer strong analgesics and to reduce intraluminal pressure using NGT, and to prepare the patient for surgical treatment before making a surgical treatment decision. The mean life expectancy in patients with inoperable MBO without surgical treatment is between four and five weeks. The life expectancy in patients undergoing palliative surgical treatment varies from three to eight months.[7,8,14] In patients who underwent palliative surgery, the median follow-up period by hospitalization was 16 days and rate of complication development was 27.1%. These rates were significantly higher than the group of patients who had medical treatment. On the other hand, patients who received palliative surgery had low recurrence rates and longer survival after treatment (Table 2). Complications and longer hospitalizations are expected in the palliative surgery group. The positive outcomes, such as decreases in nausea, vomiting, removal of NGT, and repeated hospitalizations in patients during postoperative term, were observed. The obstruction in MBO can be complete, incomplete or may involve multiple segments. In the radiological evaluation of the inoperable patients with MBO, multiple abdominal segments are involved in more than 80%, whereas diffuse peritoneal carcinomatosis is observed in the abdomen of more than 65% of the cases.[10] Before evaluating palliative surgery in our clinic, we carefully evaluate the patient’s clinical and functional status and the data from imaging modalities, such as abdominal CT. In fact, 82% ascites (p=0.003), 71.4% peritoneal involvement (p=0.001) and 78.6% visceral organ involvement (p=0.049), were observed when comparing the abdominal CT of the groups of medical treatment and palliative surgery. Peritoneal involvement in CT and the presence of malignant ascites and visceral organ metastasis played an important role in our decision-making for palliative surgery (Table 2). Therefore, the CT findings of gross mesenteric involvement may be regarded as one of the most important predictive factors of failure of surgery in MBO. We have observed that probably the single most predictive sign in CT was the cluster of the small intestine in the midline with massive shrinkage of mesenteric involvement by the peritoneal metastasis. The decision of proper treatment for MBO required a shared decision-making with the patients and families. It also needed a multidisciplinary approach among different professions (e.g., Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Akbaş et al. Does a selective surgical approach to MBO help in palliative care patients?

oncologists, surgeons, gastroenterologists, palliative care specialists and intensivists). In the multidisciplinary approach, the physical condition of patients (e.g., clinical status, performance, comorbidity and life expectancy), as well as his/her emotional and psychological status and expectations were among the important determinants. The best example of this is stoma opening or resection anastomosis procedure after resection in patients with MBO. In the treatment process, it is important that the physician, patient and his/her family cooperate in the decision-making process concerning possible conscientious and legal issues.[17] The decision-making process required several rounds of discussion with palliative care specialists, surgeons, patients and families. After obtaining all the clinical and radiological evaluation, the most important aspect of decision-making should be carried with palliative care specialists to elaborate on the patients/families expectations and goals. Our study includes some risks and limitations inherent in all retrospective studies. Lack of a standard protocol in treatment and follow-up of advanced-stage cancer patients and the need to consider the condition, comorbidity, life expectancy and CT findings of the patient when deciding on palliative surgery are some of them.

Conclusion The aim of palliative treatment is to improve the life quality of patients through the relief of the symptoms. We have shown that better outcomes in the quality of life can be achieved in highly selected MBO patients who underwent palliative surgery compared to medical treatment. To achieve improved results, a multidisciplinary team effort with more emphasis on palliative care is important. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.A., İ.O., E.D.; Design: İ.O., A.A.; Supervision: İ.O, A.A.; Resource: E.D., H.D., H.B.; Materials: H.D., M.F.D., H.B.; Data: A.A., M.F.D.; Analysis: A.A., İ.O.; Literature search: A.A., İ.O., E.D.; Writing: A.A.; Critical revision: İ.O., E.D. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Ripamonti C, Twycross R, Baines M,Bozzetti F, Capri S, De Conno F, et al. Clinical-practice recommendations for the management of bowel obstruction in patients with end-stage cancer. Support Care Cancer 2001;9:223–33.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

2. Mercadante S, Chen W. Palliativecare of bowelobstruction in cancerpatients. 2017. Available from: https://www.uptodate.com/contents/palliative-care-of-bowel-obstruction-in-cancer-patients. 3. Chen JH, Huang TC, Chang PY, Dai MS, Ho CL, Chen YC,et al. Malignant bowel obstruction: A retrospective clinical analysis. Mol Clin Oncol 2014;2:13–8. 4. Krouse RS. The international conference on malignant bowel obstruction: a meeting of the minds to advance palliative care research. J Pain Symptom Manage 2007;34:S1–6. 5. Anthony T, Baron T, Mercadante S, Green S, Chi D, Cunningham J,et al. Report of the clinical protocol committee: development of randomized trials for malignant bowel obstruction. J Pain Symptom Manage2007;34:S49–59. 6. Bateni SB, Bold RJ, Meyers FJ, Canter DJ, Canter RJ. Comparison of common risk stratification indices to predict outcomes among stage IV cancer patients with bowel obstruction undergoing surgery. J Surg Oncol 2018;117:479–87. 7. Laval G, Arvieux C, Stefani L, Villard ML, Mestrallet JP, Cardin N. Protocol for the treatment of malignant inoperable bowel obstruction: a prospective study of 80 cases at Grenoble University Hospital Center. J Pain Symptom Manage 2006;31:502–12. 8. Tuca A, Roca R, Sala C, Porta J, Serrano G, González-Barboteo J,et al. Efficacy of granisetron in the antiemetic control of nonsurgical intestinal obstruction in advanced cancer: a phase II clinical trial. J Pain Symptom Manage 2009;37:259–70. 9. Badgwell BD, Smith K, Liu P, Bruera E, Curley SA, Cormier JN. Indicators of surgery and survival in oncology inpatients requiring surgical evaluation for palliation. Support Care Cancer 2009;17:727–34. 10. Tuca A, Guell E, Martinez-Losada E, Codorniu N. Malignant bowel obstruction in advanced cancer patients: epidemiology, management, and factors influencing spontaneous resolution. Cancer Manag Res 2012;4:159–69. 11. Lilley EJ, Cauley CE, Cooper Z. Using a Palliative Care Framework for Seriously Ill Surgical Patients; The Example of Malignant Bowel Obstruction. JAMA Surg 2016;151:695–6. 12. Francescutti V, Miller A, Satchidanand Y, Alvarez-Perez A, Dunn KB. Management of bowel obstruction in patients with stage IV cancer: predictors of outcome after surgery. Ann Surg Oncol 2013;20:707–14. 13. Ripamonti CI, Easson AM, Gerdes H. Management of malignant bowel obstruction. Eur J Cancer 2008;44:1105–15. 14. Roeland E, von Gunten CF. Current concepts in malignant bowel obstruction management. Curr Oncol Rep 2009;11:298–303. 15. Dalal KM, Gollub MJ, Miner TJ,Wong WD, Gerdes H, Schattner MA,et al. Management of patients with malignant bowel obstruction and stage IV colorectal cancer. J Palliat Med 2011;14:822–8. 16. Miller G, Boman J, Shrier I, Gordon PH. Small-bowel obstruction secondary to malignant disease: an 11-year audit. Can J Surg 2000;43:353– 8. 17. Tarcan E. Cerrahi Ünitelerinde Palyatif Bakım. Turkiye Klinikleri General Surgery-Special Topics2016;9:1–7. 18. Blair SL, Chu DZ, Schwarz RE. Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol 2001;8:632–7. 19. Bryan DN, Radbod R, Berek JS. An analysis of surgical versus chemotherapeutic intervention for the management of intestinal obstruction in advanced ovarian cancer. Int J Gynecol Cancer 2006;16:125–34.

881

Akbaş et al. Does a selective surgical approach to MBO help in palliative care patients?

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Palyatif bakım hastalarında görülen malign bağırsak obstrüksiyonlarında selektif cerrahi yaklaşım fayda sağlıyor mu? Dr. Ahmet Akbaş,1 Dr. Emin Daldal,2 Dr. Fatih Daşıran,2 Dr. Hüseyin Bakır,2 Dr. Hasan Dagmura,2 Dr. İsmail Okan2 1 2

Sağlık Bilimleri Üniversitesi Bağcılar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Tokat Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tokat

AMAÇ: Malign bağırsak obstrüksiyonu (MBO) ileri evre tümörlerin karıniçi metastatik yayılımına sekonder oluşan bir durumdur. Tedavi yaklaşımında hekimler arasında tam bir konsensüs yoktur. Bu yazıda, MBO tanısı konulan hastalarda tıbbi tedavi ile palyatif cerrahi tedavi uygulanmış olan hastaların karşılaştırmalı sonuçlarını değerlendirerek hekimlerin dikkatine sunmayı amaçladık. GEREÇ VE YÖNTEM: 2010–2017 yılları arasında kanser tanısı ile tedavi gören ve cerrahi kliniğinden MBO semptomları nedeniyle konsültasyon istenen hastalar belirlenerek kaydedildi. Küratif amaçla ameliyat yapılan hastalar ile kliniğe konsülte edilen hastalardan obstrüksiyon semptomları olmayan hastalar çalışmadan çıkarıldı. Çalışmaya dahil edilen hastalara uygulanmış olan tedaviye göre cerrahi veya tıbbi tedavi olarak ikiye ayrıldı. Cerrahi tedavi gören ve tıbbi tedavi gören hastalar sağ kalım, oral gıda alımı ve semptomların düzelmesi açısından karşılaştırıldı. BULGULAR: Çalışmaya yaşları 60.5±12.8 (27–88) olan 76 (30 kadın, 46 erkek) hasta alındı. Kırk sekiz (%64.9) hastaya cerrahi tedavi uygulanırken 28 (%35.1) hastaya tıbbi tedavi uygulandı. Cerrahı tedavi uygulanan hastalar ile tıbbi tedavi uygulanan hastaların yapılan istatistiksel karşılaştırmasında cerrahi tedavi uygulanan hastaların hastanede yatış süresi uzun (median 16 güne karşılık 4 gün; p<0.001), komplikasyon oranı yüksek (%27.1’e karşı %3.5; p=0.003) iken cerrahi sonrası oral gıda alımında rahatlama (%97.9 karşı %78.6; p=0.005) ve tedavi sonrası yaşam süresi daha uzun (median 105 güne karşılık 43 gün; p=0.035) olduğu gözlendi. TARTIŞMA: Çalışma, palyatif bakım da dahil olmak üzere multidisipliner ekip tarafından değerlendirilen malign bağırsak tıkanıklığı olan hastalarda cerrahi tedavinin yaşam kalitesi parametreleri için daha iyi sonuçlara yol açtığını ortaya koymuştur. Anahtar sözcükler: İleus; malign bağırsak obstrüksiyonu; palyatif cerrahi; tümör. Ulus Travma Acil Cerrahi Derg 2020;26(6):875-882

882

doi: 10.14744/tjtes.2020.90250

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

Does primer appendagitis epiploica require surgical intervention? Barış Mantoğlu, M.D.,1 Fatih Altıntoprak, M.D.,2 Emrah Akın, M.D.,1 Necattin Fırat, M.D.,1 Emre Gönüllü, M.D.,1 Enis Dikicier, M.D.1 1

Department of General Surgery, Sakarya University Training and Research Hospital, Sakarya-Turkey

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

ABSTRACT BACKGROUND: Although primer appendagitis epiploica (PAE) is an acute condition, there is no consensus about a standard firstchoice treatment. Different non-surgical and surgical interventions for PAE are available. METHODS: In this study, a total of 39 patients who were diagnosed as PAE between 2013–2018 were evaluated retrospectively concerning recurrences of the disease, medical intervention, and the requirement of hospitalization. USG and abdominal CT were used as diagnostic tools. Patients were also evaluated for a one-month and long-term follow-up. RESULTS: Of the 39 patients, 29 were male and 10 were female. Recurrence was seen in three patients at the earliest six months. These patients responded to medical treatment. CONCLUSION: Accurate diagnosis with the help of developing imaging methods has made non-surgical treatment a viable option in the treatment of PAE. Keywords: Acute abdomen; conservative treatment; primer epiploic appendagitis.

INTRODUCTION

MATERIALS AND METHODS

Epiploic appendages (EA) are an intense form of pedicled fat tissue covered with serosa in the wall of the colon. Epiploic appendages are between 0.5 and 5 cm long, each accompanied by one or two arterioles and a venule present in the vascular stalks attached to the colon.[1] The total number of appendages varies between 50–100 and the appendages are generally adjacent to anterior and posterolateral taenia coli.[2,3] Primer appendagitis epiploica (PAE) is an acute condition that arises from torsion or spontaneous venous thrombosis that involves inflammation in the surrounding tissues due to weak arterial feeding and freely moving pedicled structures. The most common site of appendix epiploica is the sigmoid colon. Although PAE responds to conservative treatment, misdiagnosed cases may result in unnecessary laparotomies. In this paper, we suggest that PAE can be managed with conservative treatment.

The records of patients admitted to Sakarya University Faculty of Medicine Emergency Department with acute abdominal pain from 2013 through 2018 were evaluated retrospectively in this study. Files of patients diagnosed with PEA were examined in detail to ascertain demographic data, leukocyte count at presentation, C-Reactive Protein (CRP) levels, radiological examinations, and treatment processes. Abdominal ultrasonography (USG) was performed by a radiologist for all patients who presented to the emergency department or surgical outpatient clinic with abdominal pain. An abdominal computed tomography (CT) scan was sometimes performed to confirm the diagnosis, especially for older patients who could not be diagnosed using USG. After the PAE diagnosis was confirmed, patients with severe abdominal pain were hospitalized. The patients were

Cite this article as: Mantoğlu B, Altıntoprak F, Akın E, Fırat N, Gönüllü E, Dikicier E. Does primer appendagitis epiploica require surgical intervention?. Ulus Travma Acil Cerrahi Derg 2020;26:883-886. Address for correspondence: Barış Mantoğlu, M.D. Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi Genel Cerrahi Kliniği, Sakarya, Turkey Tel: +90 264 - 888 40 00 E-mail: barismantoglu@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):883-886 DOI: 10.14744/tjtes.2020.09693 Submitted: 13.10.2019 Accepted: 24.02.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

883

Mantoğlu et al. Does primer appendagitis epiploica require surgical intervention?

checked daily with hemogram and CRP controls. No control imaging was performed because there was no progression in hospitalized patients’ clinics. Intramuscular (IM) anti-inflammatory treatment was administered to hospitalized patients, while oral anti-inflammatory medication was administered to non-hospitalized patients. Non-hospitalized patients were strongly advised to contact the hospital immediately in case of severe abdominal pain. All patients diagnosed with PAE had a follow-up after one month; control imaging and examinations were performed. USG was applied as a control imaging method. Ethics committee approval of our study was obtained from our university. Data were analyzed by descriptive statistics, and percentages and numbers were used for categorical data.

RESULTS Twenty-nine of the thirty-nine patients with PAE were male, and ten were female. The mean patient age was 44.4±13.2. Ten of the thirty-nine patients (25.6%) were hospitalized (six males, four females). The mean hospitalization time was 55.2±22 hours. The mean WBC (White Blood Count) of the patients was 8730 mm3±2.65, and the mean CRP was 1.49 mg/dl±1.8. The mean body mass index (BMI) of patients was 28.91±3. Intramuscular diclofenac sodium 2×1 was given to hospitalized patients. Oral intakes of the patients proceeded. Diclofenac sodium 2×1 pills were prescribed in the twenty-nine patients who were not hospitalized. Thirty-four of the 39 patients (87.17%) came to the one-month follow up appointments, and no pathology was detected in the controls. The five patients who did not come to the follow up could not be reached, even by phone. At long term follow up, one female patient had a recurrence after six months, one male patient had a recurrence after two months, and another male patient had a recurrence twelve months later. Patients with recurrences were treated medically without surgical intervention. The recurrence rate was 8.82% in checked patients. The longest follow-up was three years. No surgical intervention was performed during the follow-up (Table 1).

weight loss have more extensive appendages.[2,11] Although PAE can be seen in any age group, even children, it is most often seen in individuals in their 40s and 50s, and men are slightly more affected than women.[12–14] Heavy exercise and obesity may also increase the risk of developing the disease. [15] The main driver of PAE is the formation of torsion and related ischemia and aseptic necrosis.[2,15,16] A spontaneous venous thrombosis is another reason for developing the disease.[17] The mean age of our patients and the mean body mass index were consistent with PAE, and positional etiologic factors, such as a sudden change of body position, were not found in our patients. Most of the patients were admitted to the emergency department with sudden onset, constant, localized, non-migratory abdominal pain, most frequently detected in the left and right lower quadrants. PAE may mimic surgical pathologies, such as acute appendicitis, acute cholecystitis, and acute diverticulitis.[13,18] Nausea and vomiting may occur. All patients admitted to our emergency department or outpatient clinic had sudden onset abdominal pain, but no nausea or vomiting. On physical examination, tenderness in the right or left lower quadrant of the abdomen was the most common finding. All of our patients had lower abdominal tenderness. Table 1. Descriptive statistics of the numerical variables Patients

n Mean±SD

Age

39 44.4±13.2

White blood cell

8731±2.65

C-reactive protein

1.49±1.8

Body mass index

28.9±3

Hospitalization 10 55.2±22 SD: Standard deviation.

Table 2. Descriptive statistics of the outpatient and hospitalized patients Patients

DISCUSSION Vesalius was first described EA in 1543, and the surgical importance of EA was noticed in 1843 by Virchow, who suggested that EA could be intraabdominal loose bodies due to their detachment.[3,4] The definition of EA was revealed in 1956 by Dockerty et al.[5] The most affected bowel segments are the sigmoid colon and ileocecum.[6,7] The exact role of these appendages is not clear, although fat storage for consumption during starvation, blood supply protection for a collapsed colon, and assistance with colonic absorption have been suggested.[8,9] The exact incidence of the disease is not known, but in one study, the incidence was reported to be 8.8 per million.[10] Nutritional status may affect EA size. Obese individuals and individuals who have had recent 884

n Mean±SD

Hospitalized Age

46.7±14.1

White blood cell

10017±2.9

C-reactive protein

2.51±2.9

Body mass index

29.6±2

Outpatient Age

43.6±13.1

82.88±2.4

White blood cell

C-reactive protein

1.14±1

Body mass index

28.6±3.2

SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

MantoÄ&#x;lu et al. Does primer appendagitis epiploica require surgical intervention?

(a)

(b)

Figure 1. (a, b) CT image of appendagitis epiploica; red arrow

Only half of our patients had rebound sensitivity. Based on a previous study, rebound sensitivity is usually not detected. [19] Laboratory test results are generally routine, although some patients may present with slightly elevated CRP and WBC.[12,13,16] In 18 of our 39 patients, we identified that CRP values were somewhat high, and nine of our patients had an increased WBC. Although PAE is usually a self-limiting disease, 10 patients were hospitalized for follow-up and their mean WBC and CRP levels were higher than those of the outpatient group. It appears that WBC and CRP values are associated with clinical hospitalization, but larger sample groups are required to prove statistical significance (Table 2a, b). In patients with suspected PAE, USG can be used as an inexpensive and non-invasive technique. The USG shows a well-defined, non-compressed hypoechoic mass lesion around the colon, with a hypoechoic rim around it. The color Doppler USG does not show blood flow within the lesion.[20,21] This result enables the differentiation of PEA from appendicitis and diverticulitis. In our case series, USG was performed first, but the success of diagnosis depends on the radiologistâ&#x20AC;&#x2122;s experience. Computed tomography is accepted as the gold standard for PAE diagnosis (Fig. 1a). Although regular EA is not observed with CT, PEA can be seen as a pedicled structure with fat density on the tomography after inflammation (Fig. 1b). Legome et al. diagnosed all patients using tomography in a 19-case series.[15,22] Twenty-nine of our patients were diagnosed with tomography because USG was not helpful in the diagnosis of these patients. Although MRI is not required for direct diagnosis, it may be useful in demonstrating the severity of inflammation in the peripheral mesenteric tissue. The differential diagnosis of PEA should be made, especially from appendicitis, diverticulitis, cholecystitis, and other pathologies that may require surgery. Diagnosis of PAE can easily be made by increasing the use of tomography, and raUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

diologists should keep in mind the presence of this rare disease.[23,24] The treatment of PAE is still controversial. PAE is generally known as a self-limiting condition in which patients have a full recovery with anti-inflammatory drugs in a few weeks. [20] Surgical therapy is favorable to prevent recurrence due to inflammation-induced adhesions, and other less common complications. Laparoscopic intervention is usually the first choice.[25] Although Epstein and Lempke first described the nonsurgical management of PAE in 1968, it was not reported until 1992.[26,27] Although some studies have reported that conservative treatment causes high rates of recurrence, our recurrence rate was only 8.82% (3 of 34), and these relapsed cases were treated medically without any complication. Unnecessary surgical intervention should be avoided and side effects, such as severe bleeding, organ injury, and allergic reaction to anesthetic drugs, should be discussed with patients. In addition, conservative medical treatment of PAE is much more cost-effective than surgical intervention.

Conclusion Increased use of imaging methods, such as tomography and USG, can aid correct diagnosis of PAE. We believe that conservative medical treatment of PAE is a good alternative to surgery. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: B.M.; Design: B.M.; Supervision: F.A.; Resource: E.D.; E.A.; Materials: N.F.; Data: E.G., E.A.; Analysis: E.G., B.M.; Literature search: E.D., N.F.; Writing: B.M.; Critical revision: F.A. Conflict of Interest: None declared. 885

Mantoğlu et al. Does primer appendagitis epiploica require surgical intervention?

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

REFERENCES 1. Ross JA. Vascular loops in the appendices epiploicae; their anatomy and surgical significance, with a review of the surgical pathology of appendices epiploicae. Br J Surg 1950;37:464–6. 2. Pines BR, Rabinovitch J, Beller SB. Primary torsion and infarction of the appendices epiploicae. Arch Surg 1941;42:775–87. 3. Vinson DR. Epiploic appendagitis: a new diagnosis for the emergency physician. Two case reports and a review. J Emerg Med 1999;17:827–32. 4. Vesalius A. Andreae vesalii bruxellensis, scholae medicorum patauiniae professoris de humani corporis fabricia libri septem. Basel, Switzerland: Basileae: Ex officina Joannis Oporini; 1543. 5. Dockerty MB, Lynn TE, Waugh JM. A clinicopathologic study of the epiploic appendages. Surg Gynecol Obstet 1956;103:423–33. 6. Legome EL, Sims C, Rao PM. Epiploic appendagitis: adding to the differential of acute abdominal pain. J Emerg Med 1999;17:823–6. 7. Hiller N, Berelowitz D, Hadas-Halpern I. Primary epiploic appendagitis: clinical and radiological manifestations. Isr Med Assoc J 2000;2:896–8. 8. Schnedl WJ, Krause R, Tafeit E, Tillich M, Lipp RW, Wallner-Liebmann SJ. Insights into epiploic appendagitis. Nat Rev Gastroenterol Hepatol 2011;8:45–9. 9. Marinis TP, Cheek JH. Primary Inflammation of the Appendices Epiploicae : With Review of the Literature and Report of Six Additional Cases. Ann Surg 1949;129:533–7. 10. de Brito P, Gomez MA, Besson M, Scotto B, Huten N, Alison D. Frequency and epidemiology of primary epiploic appendagitis on CT in adults with abdominal pain. [Article in French]. J Radiol 2008;89:235–43. 11. Ghahremani GG, White EM, Hoff FL, Gore RM, Miller JW, Christ ML. Appendices epiploicae of the colon: radiologic and pathologic features. Radiographics 1992;12:59–77. 12. Ozdemir S, Gulpinar K, Leventoglu S, Uslu HY, Turkoz E, Ozcay N, et al. Torsion of the primary epiploic appendagitis: a case series and review of the literature. Am J Surg 2010;199:453–8. 13. Sand M, Gelos M, Bechara FG, Sand D, Wiese TH, Steinstraesser L, et

al. Epiploic appendagitis--clinical characteristics of an uncommon surgical diagnosis. BMC Surg 2007;7:11. 14. Toprak H, Yildiz S, Kilicarslan R, Bilgin M. Epiploic appendagitis. J Belgian Society Radiology 2014;97:174–5. 15. Mollà E, Ripollés T, Martínez MJ, Morote V, Roselló-Sastre E. Primary epiploic appendagitis: US and CT findings. Eur Radiol 1998;8:435–8. 16. Legome EL, Belton AL, Murray RE, Rao PM, Novelline RA. Epiploic appendagitis: the emergency department presentation. J Emerg Med 2002;22:9–13. 17. Thomas JH, Rosatto FE, Peterson LT. Epiploic appendagitis. Surgery, Gynecology & Obstetrics 1974;138:23–5. 18. Lien WC, Lai TI, Lin GS, Wang HP, Chen WJ, Cheng TY. Epiploic appendagitis mimicking acute cholecystitis. Am J Emerg Med 2004;22:507–8. 19. McMahon AJ, Hansell DT. Primary appendicitis epiploicae mimicking acute appendicitis. Postgrad Med J 1988;64:903–5. 20. Singh AK, Gervais DA, Hahn PF, Sagar P, Mueller PR, Novelline RA. Acute epiploic appendagitis and its mimics. Radiographics 2005;25:1521–34. 21. Rao PM, Wittenberg J, Lawrason JN. Primary epiploic appendagitis: evolutionary changes in CT appearance. Radiology 1997;204:713–7. 22. Uslu Tutar N, Ozgül E, Oğuz D, Cakir B, Tarhan NC, et al. An uncommon cause of acute abdomen--epiploic appendagitis: CT findings. Turk J Gastroenterol 2007;18:107–10. 23. Hasbahceci M, Erol C, Seker M. Epiploic appendagitis: is there need for surgery to confirm diagnosis in spite of clinical and radiological findings?. World J Surg 2012;36:441–6. 24. Chu EA, Kaminer E. Epiploic appendagitis: A rare cause of acute abdomen. Radiol Case Rep 2018;13:599–601. 25. Vázquez-Frias JA, Castañeda P, Valencia S, Cueto J. Laparoscopic diagnosis and treatment of an acute epiploic appendagitis with torsion and necrosis causing an acute abdomen. JSLS 2000;4:247–50. 26. Epstein LI, Lempke RE. Primary idiopathic segmental infarction of the greater omentum: case report and collective review of the literature. Ann Surg 1968;167:437–43. 27. Puylaert JB. Right-sided segmental infarction of the omentum: clinical, US, and CT findings. Radiology 1992;185:169–72.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Primer appendagitis epiploica da cerrahi müdahale gerektirir mi? Dr. Barış Mantoğlu,1 Dr. Fatih Altıntoprak,2 Dr. Emrah Akın,1 Dr. Necattin Fırat,1 Dr. Emre Gönüllü,1 Dr. Enis Dikicier1 1 2

Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Sakarya Sakarya Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Sakarya

AMAÇ: Primer apendajitis epiploica (PAE) akut bir hastalık olmasına rağmen, standart bir birinci seçenek tedavi konusunda fikir birliği yoktur. PAE için farklı cerrahi ve cerrahi olmayan girişimler mevcuttur. GEREÇ VE YÖNTEM: 2013–2018 yılları arasında PAE tanısı almış toplam 39 hasta geriye dönük olarak hastalığın nüksü, tıbbi müdahale ve hastanede yatış gereksinimi açısından değerlendirildi. Ultrasonografi ve abdominal bilgisayarlı tomografi tanı aracı olarak kullanıldı. Hastalar ayrıca bir aylık ve uzun süreli takipler için değerlendirildi. BULGULAR: Otuz dokuz hastanın 29’u erkek, 10’u kadındı. En erken altı ayda üç hastada nüks görüldü. Bu hastaların tümü nüks edenler dahil tıbbi tedaviye cevap verdi. TARTIŞMA: Görüntüleme yöntemlerinin gelişmesi ile doğru tanın konulabilmesi mümkün olabilmekte ve sonuç olarak, cerrahi müdahale gerektirmeden tıbbi tedavi ile PAE tedavisinde uygulanabilir bir seçenek haline getirmektedir. Anahtar sözcükler: Akut karın; konservatif tedavi; primer epiploik apendajitis. Ulus Travma Acil Cerrahi Derg 2020;26(6):883-886

886

doi: 10.14744/tjtes.2020.09693

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

The evaluation of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in anorectal abscess Çağrı Akalın, M.D. Deparment of General Surgery, Ordu University Training and Research Hospital, Ordu-Turkey

ABSTRACT BACKGROUND: Anorectal abscess (ARA) is a commonly observed surgical situation. Our aim is to evaluate neutrophil-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in ARA. METHODS: From January 2014 to March 2019, patients diagnosed with ARA were retrospectively analysed, and a patient group was formed. Healthy individuals were included in this study as a control group. The demographic characteristics, completed blood count (CBC) and c-reactive protein (CRP) values of patients were analysed. Localisation of abscess in patients was assessed using computed tomography results. From CBC parameters, white blood count (WBC), NLR and PLR values were identified. The cut-off values for data, sensitivity and specificity were identified using the receiver operating curve (ROC) analyses. RESULTS: In the patient group, WBC, CRP, NLR and PLR values were identified to be statistically significantly increased (p<0.001). When supralevator abscess localisation was compared with other ARA localisations, there was a statistically significant difference for WBC (p=0.003), but no statistically significant differences were identified for CRP, NLR and PLR (p>0.05). ROC analysis found WBC had cut-off value of 9.99 103/μL for ARA diagnosis with 95% sensitivity and 95% specificity, a CRP had 2.5 mg/dL cut-off value with 88% sensitivity and 95% specificity, NLR had a cut-off of 3.96 with a sensitivity of 82% and specificity of 95% and PLR had a cut-off value of 112.84 with a sensitivity of 71% and specificity of 68%. CONCLUSION: We believe NLR may be used as a helpful diagnostic marker for ARA diagnosis; however, PLR has low sensitivity and specificity. Keywords: Anorectal abscess; neutrophil to lymphocyte ratio; platelet to lymphocyte ratio; sensitivity; specificity.

INTRODUCTION Anorectal abscess (ARA) is a common surgical condition that requires incision and drainage for treatment.[1] Although ARA usually manifests itself as pain, tenderness and erythema in the rectal region, symptoms, such as fever and malaise, are more prominent with deep abscesses.[2] ARA is associated with increased morbidity and mortality if not treated in the early period.[3] For the diagnosis of ARA, traditional markers, such as white blood cell count (WBC) and C-reactive protein (CRP), as well as assistive imaging methods, such as magnetic resonance imaging and computed tomography (CT), are used.[4,5] Neutrophil to lymphocyte ratio (NLR) and platelet to lympho-

cyte ratio (PLR) are inexpensive, non-invasive and easily calculated markers obtained from peripheral blood analysis. In the event of inflammation, the immune response in the systemic circulation is in the form of neutrophilia and lymphopenia, on which the use of NLR and PLR as diagnostic markers is generally based.[6,7] There are studies in which NLR and PLR were used as helpful diagnostic markers for the diagnosis and prognosis of diseases and infections with systemic inflammation.[8,9] The present study aims to research the use of NLR and PLR, accompanied by traditional inflammatory markers, as helpful diagnostic markers for diagnosis of ARA.

Cite this article as: Akalın Ç. The evaluation of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in anorectal abscess. Ulus Travma Acil Cerrahi Derg 2020;26:887-892. Address for correspondence: Çağrı Akalın, M.D. Ordu Üniversitesi Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Ordu, Turkey Tel: +90 452 - 225 01 86 / 1566 E-mail: dr.cagriakalin@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):887-892 DOI: 10.14744/tjtes.2020.04501 Submitted: 30.05.2019 Accepted: 29.03.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

887

Akalın. Evaluation of NLR and PLR in anorectal abscess

MATERIALS AND METHODS Ethical approval for this study was obtained from the Clinical Research Ethics Committee of Ordu University, Faculty of Medicine (Approval number: 2019/75, Date: 09/05/2019). We retrospectively analyzed patients diagnosed with ARA who were operated in two hospitals of Ordu between January 2014 and March 2019. Age, gender, symptoms, duration of symptoms, type of anaesthesia, CT results, complete blood count (CBC) and CRP results were recorded. The exclusion criteria were as follows: patients under 18 years of age, pregnant women, patients with chronic diseases which might affect NLR and PLR (diabetes mellitus, hypertension, inflammatory bowel disease, haematological diseases, coronary artery disease, chronic renal and hepatic failure), patients who were administered medicine which could affect the CBC parameters (intravenous immunoglobulin and thyramazole), patients with malignancy, and patients whose information was inaccessible. The control patients consisted of healthy individuals applying to the general surgery outpatient clinic who did not use any medication. ARA patients were referred to as the patient group and the control patients as the control group. Patient information was obtained from hospital information systems and patient files. Abdominopelvic CT scan results were used to evaluate ARA localisations, and abscess localisations were classified as submucosal, intersphincteric, ischiorectal and supralevator abscesses. Laboratory parameters were examined at time of first attendance (before medical and surgical treatment). Venous blood samples for CBC were collected in tubes containing two milliliters (mL) of ethylene-diamine tetra-acetic acid and analysed in an automated haematology analyser device (Sysmex XN-1000, Sysmex Corporation, Kobe, Japan). For CRP, venous blood samples were collected in empty tubes and analysed in a Cobas 6000 autoanalyzer (Roche, Mannheim, Germany). CBC and CRP values were evaluated according to the reference range accepted by the hospital haematology laboratory. WBC value was calculated using the parameters obtained from the CBC analysis. NLR was calculated by dividing the neutrophil count by lymphocyte count, and PLR was obtained by dividing platelet count by lymphocyte count. Patient symptoms were categorised as pain, swelling, fever and general status disorder. Oral intake was stopped in the preoperative period. Patients began analgesic (paracetamol, nonsteroidal anti-inflammatories, opioids), antibiotic (ciprofloxacin 500 mg + metronidazole 500 mg / ampicillin+sulbactam 1.5 g) and fluid treatment according to clinical status and surgeon choice. The operations were performed by general surgeons in operating room conditions under local anaesthesia or general anaesthesia. Tests were requested for local anaesthesia according to surgeon choice (haemogram, biochemical, coagulation, ELISA), while preoperative tests were requested for patients who were operated under general anaesthesia (haemogram, biochemical, coagulation, ELISA (Hb888

sAg, anti-HCV, anti-HIV), posteroanterior lung radiography and electrocardiogram).

Statistical Analysis Data were analysed using SPSS (Statistical Package for Social Sciences) Version 20 for Windows® (Chicago, IL, USA). Whereas the descriptive statistics for continuous variables in our study are expressed as mean, median, standard deviation, minimum and maximum values; they are expressed as number and percentage for categoric variables. The data distribution was evaluated using the Kolmogorov-Smirnov test. Mann-Whitney U and Kruskal-Wallis test were performed for continuous variables. The chi-square test was used to determine the relationship between categoric variables. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cut-offs for NLR and PLR, with specificities, sensitivities, and overall accuracies calculated. P-value <0.05 was considered statistically significant.

RESULTS Of the 302 patients in this study, 157 (52%) were in the control group and 145 (48%) were in the patient group. Of these patients, 104 (34.4%) were female and 198 (65.56%) were male. Of the 145 patients in the patient group, 44 (28%) were female and 101 (72%) were male, while of the 157 patients in the control group, 60 were female (41.4%) and 97 were male (68.6%). The mean age was 38.33±10.01 years in the study group, 39.77±10.18 years in the patient group and 36.99±9.69 years in the control group. There was no statistically significant correlation between the groups concerning age and gender (p>0.05). Of the patients, 28 (19.3%) were operated under local anaesthesia, while 117 (80.7%) were operated under general anaesthesia. When the symptoms of 145 patients were examined, 139 had pain (95.8%), 111 had swelling (76.5%), 71 had fever (48.9%) and five had disrupted general status (3.4%). The symptom duration was first 24 hours for 66 patients (45.6%), 24-48 hours in 34 patients (23.4%), 48-72 hours in 29 patients (20%) and >72 hours for 16 patients (11%). When the symptom durations and laboratory parameters of patients were investigated, there was clinically significant elevation in all parameters with the increase in symptom duration; however, only the CRP value was significantly different (p<0.05). The correlation between duration of symptoms and laboratory parameters of patients is shown in Table 1. The mean platelet count was determined as 245.55±50.17 109/L in the patient group, and 218.68±42.21 109/L in the control group. There was a statistically significant difference in WBC, CRP, NLR and PLR values between the groups (p<0.05). WBC, CRP, NLR and PLR values of the patients are given in Table 2. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Akalın. Evaluation of NLR and PLR in anorectal abscess

In total, perianal abscess was detected in 75 (51.7%) patients, intersphincteric abscess in 32 (22.1%), ischiorectal abscess in 30 (20.7%), and supralevator abscess in eight (5.5%). The comparison of supralevator abscess localisation and other ARA localisations revealed a statistically significant difference in WBC (p<0.05), while there was no statistically significant difference in CRP, NLR and PLR (p>0.05). The relationship between WBC, CRP, NLR, PLR and abscess localisations in the patients is given in Table 3.

In the ROC analysis, for the diagnosis of ARA, the cut-off value of 9.99 for WBC had 95% sensitivity and 95% specificity, the cut-off value of 2.5 mg/dL for CRP had 88% sensitivity and 95% specificity, the value of 3.96 for NLR had 82% sensitivity and 95% specificity, and the cut-off value of 112.84 for PLR had 71% sensitivity and 68% specificity. The area under the ROC curve (AUC) values of WBC, CRP, NLR, and PLR for predicting ARA and other data in the ROC curve are demonstrated in Table 4.

The evaluation of the ROC analysis revealed a statistically significant difference in WBC, CRP, NLR and PLR between the groups (p<0.001). The ROC curve, containing the WBC, CRP, NLR and PLR data in the study group, is given in Figure 1.

DISCUSSION For diagnosis of ARA, in addition to physical examination and assisting radiologic investigations, helpful diagnostic markers like WBC and CRP are commonly used. Early di-

Table 1. WBC, CRP, NLR and PLR values according to symptom duration Variables

0–24 h (n=66)

24–48 h (n=34)

48–72h (n=29)

>72h (n=16)

p-value*

Mean±SD Mean±SD Mean±SD Mean±SD

WBC (103/μL)

13.19±1.70

C-reactive protein (mg/dL)

3.21±0.89

4.12±1.92

NLR

9.47±6.03

12.15±8.09

PLR

157.06±52.21

168.32±52.14

160.62±51.47

13.28±2.39

13.95±4.43

17.47±7.83

0.13

5.59±4.87

10.89±9.87

<0.001

14.82±7.91

18.58±10.29

0.19

192.86±54.09

0.17

*The Kruskal-Wallis test was used, and p-values of less than 0.05 were regarded as statistically significant. h: Hours; WBC: White blood count; CRP: C-reactive protein; NLR: Neutrophil lymphocyte ratio; PLR: Platelet lymphocyte ratio; SD: Standard deviation.

Table 2. WBC, CRP, NLR and PLR values of the patients Variables WBC (103/μL) CRP (mg/dL)

Patient group (n=145)

Control group (n=157)

p-value*

Mean±SD (min-max)

13.84±3.82 (2.55–38.61)

7.37±1.69 (3.87–11.41)

<0.001

4.71±4.85 (0.1–35.78)

0.88±0.77 (0.1–4.45)

<0.001

NLR

11.47±8.07 (1.22–48.37)

2.21±1.03 (0.66–8.90)

<0.001

PLR

164.36±52.86 (98.50–282.33)

108.13±38.15 (52.71–264.08)

<0.001

*The Mann-Whitney U test was used, and p-values of less than 0.05 were regarded as statistically significant. WBC: White blood count; CRP: C-reactive protein; NLR: Neutrophil lymphocyte ratio; PLR: Platelet lymphocyte ratio; SD: Standard deviation.

Table 3. Abscess localisations and WBC, CRP, NLR and PLR values Variables

Perianal abscess

Intersphincteric abscess

Ischiorectal abscess

Supravelator abscess

p-value*

Mean±SD Mean±SD Mean±SD Mean±SD

WBC (103/μL) 13.11±2.87

13.70±3.15

14.25±3.71

19.53±8.24

0.003

CRP (mg/dL)

4.35±3.31

4.16±2.38

9.22±11.31

0.35

12.03±7.22

15.62±6.57 0.13

NLR PLR

4.59±4.94

10.46±7.88 12.35±9.08 161.01±53.35 159.95±52.88

172.10±55.86 184.37±34.05 0.44

*The Kruskal-Wallis test was used, and P values of less than 0.05 were regarded as statistically significant. WBC: White blood count; CRP: C-reactive protein; NLR: Neutrophil lymphocyte ratio; PLR: Platelet lymphocyte ratio; SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

889

Akalın. Evaluation of NLR and PLR in anorectal abscess

ROC Curve

1.0

Source of the Curve WBC CRP NLR PLR Reference Line

Sensitivity

0.8

0.6

0.4

0.2

0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Diagonal segments are produced by ties.

Figure 1. Receiver operating characteristic curve for WBC, CRP, NLR and PLR data in the study group.

agnosis is crucial for ARA since prolonged diagnosis and treatment results in poor prognosis in patients. As a result, helpful diagnostic markers for clinicians guiding ARA diagnosis will provide reduced morbidity and mortality. In this study, the findings showed that NLR has high sensitivity and specificity with WBC and CRP for the diagnosis of ARA, and NLR can be used as a helpful diagnostic marker. PLR has been identified to have low sensitivity and specificity for diagnosis of ARA. Currently, conditions such as infection and malignancy with high morbidity and mortality rates, have led to the search for new markers. In addition to changes in the neutrophil and lymphocyte counts in response to inflammation, the findings showed that platelets were rich in proinflammatory agents and were able to release active microparticles in case of inflammation.[10] Platelet counts are associated with platelet volume and reactivity, and can be used to reveal the presence of co-morbidities and inflammatory diseases.[11,12] Moreover, recent studies showed that platelets contribute to host defense through granules secreted and their count increases in the case of acute infection.[13,14] Such conditions developing in response to inflammation and infections have paved the way

for the use of NLR and PLR as diagnostic markers in recent years. In the event that surgical intervention is not carried out for ARA, it may result in complications such as perianal sepsis and Fournier’s gangrene.[3] Kahramanca et al.[15] investigated the correlation between the number of debridement in Fournier’s gangrene, Fournier’s gangrene severity index and NLR/PLR, and they found that NLR and PLR were significant in predicting the number of debridement. Although Fournier’s gangrene is a complication that arises from ARA, the presence of an infection identical to Fournier’s gangrene in ARA and high WBC and CRP values in our study made us think of this context. On the other hand, the findings showed that supralevator abscess was the only one in which WBC was significant among other ARA localisations. We think that this statistical difference that arose from the diagnosis of supralevator abscess was prolonged as it is deeply located. Kahramanca et al. did not find any significant correlation between the severity index of the disease and NLR and PLR, which was similar to our study in which no correlation was found between supralevator abscess and NLR and PLR. Similarly, NLR and PLR were statistically significant for the diagnosis of ARA. Kaplan et al.[16] investigated the combination of NLR and PLR in patients with pancreatitis in 2018, and they found that the combination was statistically significant when used as a diagnostic marker in pancreatic abscess. In the study conducted by Yıldırım et al., NLR and PLR increased the diagnostic value for tubo-ovarian abscess.[17] In a study of 1067 patients conducted by Kahramanca et al.,[18] the findings showed that NLR could be used as a diagnostic marker for the diagnosis of acute appendicitis and might help clinical evaluation of perforated/gangrenous appendicitis. In the study performed by Şentürk et al.,[19] the findings showed that NLR was significantly higher in patients with abscess before treatment when control patients were compared to patients with peritonsillar abscess. Moreover, in the study conducted by Seckin et al.,[20] they reported that for a NLR cut-off value of 2.67, 87% sensitivity and 82% specificity could be reached for the diagnosis of pelvic inflammatory disease (PID). However, for the PLR cut-off value of 131.548, 65% sensitivity and 66% specificity were found in for diagnosis for PID. All

Table 4. Area under the ROC curve of each tested marker Markers

AUC

Standard error

p-value

95% Confidence interval Lower limit

Upper limit

White blood cell (103/μL)

0.975 0.012 <0.001 0.952

0.997

C-reactive protein (mg/dL)

0.976

0.991

0.007

<0.001

0.962

Neutrophil to lymphocyte ratio

0.932

0.015

<0.001

0.903

0.961

Platelet to lymphocyte ratio

0.822

0.023

<0.001

0.776

0.868

AUC: Area under the receiver operating characteristic curve; μL: Microliter; mg: Miligram, dL: deciliter.

890

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Akalın. Evaluation of NLR and PLR in anorectal abscess

of these studies commonly investigated the correlation between abscess and NLR/PLR, and the results were similar to those in our study. There are some limitations in our study. First of all, the retrospective nature of this study and the limited number of patients are among the limitations. Another limitation is the absence of cytokines or other acute phase reactants as inflammatory markers in the study. On the other hand, there are some advantages. In the literature, to our knowledge, there is no study showing the correlation between ARA and NLR and PLR. In addition, we think that the inclusion of ARA by classifying based on localisations in this study is another advantage. In conclusion, we believe NLR may be used as a helpful diagnostic marker to guide clinicians in the diagnosis of ARA, while PLR had low sensitivity and specificity.

Acknowledgements I would like to thank Dr. Hakan Peker, Dr. Hüseyin Şahin, Dr. Selim Akçay, Dr. Atila Öztürk, Dr. Hamdi Tütüncü from the General Surgery Department of Centers for providing the patients’ medical record and support in accessing patient information. Ethics Committee Approval: Approved by the local ethics committee. (Approval number: 2019/75, Date: 09/05/2019). Additionally, written institutional permission was obtained from the Ordu Province Health Directorate and hospital administrations. Peer-review: Internally peer-reviewed. Conflict of Interest: None declared. Financial Disclosure: The author declared that this study has received no financial support.

REFERENCES 1. Billingham RP, Isler JT, Kimmins MH, Nelson JM, Schweitzer J, Murphy MM. The diagnosis and management of common anorectal disorders. Curr Probl Surg 2004;41:586–645. 2. Abcarian H. Anorectal infection: abscess-fistula. Clin Colon Rectal Surg. 2011;24:14–21. 3. Yilmazlar T, Ozturk E, Ozguc H, Ercan I, Vuruskan H, Oktay B. Fournier’s gangrene: an analysis of 80 patients and a novel scoring system. Tech Coloproctol 2010;14:217–23. 4. Ulug M, Gedik E, Girgin S, Celen MK, Ayaz C. The evaluation of bacteriology in perianal abscesses of 81 adult patients. Braz J Infect Dis 2010;14:225–9. 5. Khati NJ, Sondel Lewis N, Frazier AA, Obias V, Zeman RK, Hill MC.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

CT of acute perianal abscesses and infected fistulae: a pictorial essay. Emerg Radiol 2015;22:329–35. 6. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102:5–14. 7. Shimoyama Y, Umegaki O, Agui T, Kadono N, Minami T. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are superior to other inflammation-based prognostic scores in predicting the mortality of patients with gastrointestinal perforation. JA Clin Rep 2017;3:49. 8. de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 2010;14:R192 9. Kartal O, Kartal AT. Value of neutrophil to lymphocyte and platelet to lymphocyte ratios in pneumonia. Bratisl Lek Listy 2017;118:513–6. 10. Scherlinger M, Guillotin V, Truchetet ME, Contin-Bordes C, Sisirak V, Duffau P, et al. Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets. Autoimmun Rev 2018;17:625–35. 11. Abdel Galil SM, Edrees AM, Ajeeb AK, Aldoobi GS, El-Boshy M, Hussain W. Prognostic significance of platelet count in SLE patients. Platelets 2017;28:203–7. 12. Lood C, Tydén H, Gullstrand B, Nielsen CT, Heegaard NH, Linge P, Jönsen A, et al. Decreased platelet size is associated with platelet activation and anti-phospholipid syndrome in systemic lupus erythematosus. Rheumatology (Oxford) 2017;56:408–16. 13. Klinger MH, Jelkmann W. Role of blood platelets in infection and inflammation. J Interferon Cytokine Res 2002;22:913–22. 14. Rose SR, Petersen NJ, Gardner TJ, Hamill RJ, Trautner BW. Etiology of thrombocytosis in a general medicine population: analysis of 801 cases with emphasis on infectious causes. J Clin Med Res 2012;4:415–23. 15. Kahramanca S, Kaya O, Özgehan G, Irem B, Dural I, Küçükpınar T, et al. Are neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as effective as Fournier’s gangrene severity index for predicting the number of debridements in Fourner’s gangrene?. Ulus Travma Acil Cerrahi Derg 2014;20:107–12. 16. Kaplan M, Ates I, Oztas E, Yuksel M, Akpinar MY, Coskun O, et al. A New Marker to Determine Prognosis of Acute Pancreatitis: PLR and NLR Combination. J Med Biochem 2018;37:21–30. 17. Yildirim M, Turkyilmaz E, Avsar AF. Preoperative Neutrophil-to-Lymphocyte Ratio Has a Better Predictive Capacity in Diagnosing Tubo-Ovarian Abscess. Gynecol Obstet Invest 2015;80:234–9. 18. 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. 19. Şentürk M, Azgın İ, Övet G, Alataş N, Ağırgöl B, Yılmaz E. The role of the mean platelet volume and neutrophil-to-lymphocyte ratio in peritonsillar abscesses. Braz J Otorhinolaryngol 2016;82:662–7. 20. Seckin KD, Karsli MF, Yucel B, Ozkose B, Yildirim D, Cetin BA, et al. Neutrophil lymphocyte ratio, platelet lymphocyte ratio and mean platelet volume; which one is more predictive in the diagnosis of pelvic inflammatory disease? Gynecol Obstet Reprod Med 2015;21:150–4.

891

Akalın. Evaluation of NLR and PLR in anorectal abscess

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Anorektal apsede nötrofil lenfosit oranı ve trombosit lenfosit oranının değerlendirilmesi Dr. Çağrı Akalın Ordu Üniversitesi Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Ordu

AMAÇ: Anorektal apse (ARA) yaygın görülen cerrahi bir durumdur. Amacımız ARA’da nötrofil lenfosit oranı (NLO) ve platelet lenfosit oranını (PLO) değerlendirmektir. GEREÇ VE YÖNTEM: Ocak 2014–Mart 2019 tarihleri arasında ARA tanılı hastalar geriye dönük olarak analiz edilip hasta grubu oluşturuldu. Kontrol grubu için sağlıklı bireyler çalışmaya dahil edildi. Grupların demografik özellikleri, tam kan sayımı (CBC), C-reaktif protein (CRP) değerleri olarak analiz edildi. Hastaların apse lokalizasyonu için bilgisayarlı tomografi sonuçları değerlendirildi. CBC’teki parametrelerden beyaz küre sayısı (WBC), NLO ve PLO değerleri saptandı. Receiver operating characteristic (ROC) analizi ile verilerin kestirim değerleri, duyarlılık ve özgüllüğü saptandı. BULGULAR: Hasta grubunda WBC, CRP, NLO ve PLO değerleri istatistiksel olarak anlamlı derecede yüksek saptandı (p<0.001). Hastaların supralevator apse lokalizasyonu ile diğer ARA lokalizasyonları karşılaştırıldığında WBC’de istatistiksel olarak anlamlı fark saptanırken (p=0.003), CRP, NLO ve PLO’da istatistiksel olarak anlamlı fark saptanmadı (p>0.05). ROC analizinde, ARA tanısı için, WBC’de 9.99 103/μL kestirim değerinin %95 duyarlılık, %95 özgüllüğe; CRP’de 2.5 mg/dL kestirim değerinin %88 duyarlılık, %95 özgüllüğe; NLO’da 3.96 cutoff değerinin %82 duyarlılık, %95 özgüllüğe; PLO’da 112.84 cutoff değerinin %71 duyarlılık ve %68 özgüllüğe sahip olduğu belirlendi. TARTIŞMA: ARA tanısında NLO’nun tanıya yardımcı bir belirteç olarak kullanılabileceğini fakat PLO’nun ise düşük sensitive ve spesiviteye sahip olduğunu düşünmekteyiz. Anahtar sözcükler: Anorektal apse; duyarlılık; nötrofil lenfosit oranı; özgüllük; trombosit lenfosit oranı. Ulus Travma Acil Cerrahi Derg 2020;26(6):887-892

892

doi: 10.14744/tjtes.2020.04501

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

APACHE II or INCNS to predict mortality in traumatic brain injury: A retrospective cohort study Güven Gürsoy, M.D.,1 Canan Gürsoy, M.D.,2 Semra Gümüş Demirbilek, M.D.3

Yağmur Kuşcu, M.D.,3

Department of Neurosurgery, Muğla Sıtkı Koçman University Training and Research Hospital, Muğla-Turkey

Division of Intensive Care, Department of Anesthesiology and Reanimation, Muğla Sıtkı Koçman University Training

and Research Hospital, Muğla-Turkey 3

Department of Anesthesiology and Reanimation, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, Turkey

ABSTRACT BACKGROUND: Some scoring systems, such as Acute Physiology and Chronic Health Evaluation II (APACHE II), are used to predict mortality, but they are not specialized for traumatic brain injury. INCNS is a new scoring system for traumatic brain injury developed by Goa et al. INCNS score evaluates inflammation, nutrition, consciousness, neurological function and systemic condition. The present study aims to evaluate performances of Acute Physiology and Chronic Health Evaluation II (APACHE II) and INCNS to predict mortality in traumatic brain injuries. METHODS: In this study, 78 patients who were treated in anaesthesiology intensive care unit with the diagnosis of traumatic brain injury were included. Patients under the age of 18, foreigners, patients with incomplete data were excluded from this study. Medical records were examined retrospectively. APACHE II and INCNS scores in the first 24 hours were counted up. RESULTS: Of the 78 patients, 45 (57.7%) were males and 33 (42.3%) were females. The overall mortality was 34.6% (27/78). The mean APACHE II, INCNS score was 23.85±9.44 and 14.43±8.75, respectively. The area under the curve result of receiver operating characteristic curve analysis was 0.797 for the APACHE II and 0.847 for the INCNS. CONCLUSION: The INCNS scoring system had higher discriminatory power than the APACHE II in predicting the mortality of TBI in the ICU. INCNS can be considered as a usable prognostic model for Turkish people. Keywords: Acute Physiology and Chronic Health Evaluation II (APACHE II); INCNS scoring system; intensive care unit mortality; scoring system; traumatic brain injury.

INTRODUCTION Traumatic brain injury (TBI) is the main reason of mortality and neurological disabilities all over the world.[1,2] TBI is common in both low income and high-income countries and affects all ages and genders.[2] Accurate and reliable prognostic scores in traumatic brain injury may allow the clinician to summarize clinical findings, to determine the severity of the situation, to categorize disease, thus leading to account for treatment targets, treatment expectancy and prognosis while providing information to patients and their families. There-

fore, the search for an effective, reliable and easily applicable scoring system continues. Acute Physiology and Chronic Health Evaluation II (APACHE II)[3] is a frequently used scoring system for predicting mortality in general intensive care units. However, APACHE II is not specific to the disease but includes only the Glasgow Coma Score (GCS) for TBI.[4] Specifically for TBI, there are some scoring systems; GCS,[4] Full Outline of Unresponsiveness Score (FOUR),[5] Interna-

Cite this article as: Gürsoy G, Gürsoy C, Kuşcu Y, Gümüş Demirbilek S. APACHE II or INCNS to predict mortality in traumatic brain injury: A retrospective cohort study. Ulus Travma Acil Cerrahi Derg 2020;26:893-898. Address for correspondence: Canan Gürsoy, M.D. Muğla Sıtkı Koçman Üniversitesi Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Muğla, Turkey Tel: +90 252 - 214 13 23 E-mail: gursoycanan@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(6):893-898 DOI: 10.14744/tjtes.2020.22654 Submitted: 19.12.2019 Accepted: 29.02.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

893

Gürsoy et al. APACHE II or INCNS to predict mortality in traumatic brain injury

tional Mission for Prognosis and Analysis of Clinical Trials in TBI model (IMPACT)[6] or Rotterdam Scoring System,[7] the data obtained by the evaluation of the computed tomography images at Helsinki Computerized Tomography scoring system.[1] However, although all these scoring systems are powerful in determining the severity of TBI, they may be insufficient to determine the prognosis due to deficiencies in systemic evaluation. Gao et al.[8] developed Infection-Nutrition-Consciousness-Neurologic Function- Systemic Condition (INCNS) based on insufficient prognostic scores in neurocritical patients. INCNS score evaluates inflammation, nutrition, consciousness, neurological function and systemic condition (Table 1).[8] In this study, our aim is to evaluate the performance of INCNS in predicting outcomes in patients with TBI and to examine its results in the Turkish population.

MATERIALS AND METHODS After obtaining approval from the ethical committee for clinical research of Muğla Sıtkı Koçman University on 22/08/2019 (approval number: 10-VII), from 2017 to 2019, adults with TBI who were admitted to the Anesthesiology Intensive Care Unit of Muğla Sıtkı Koçman University Research and Training Hospital were enrolled in our study. Medical records of 97 isolated TBI patients were reviewed retrospectively. Patients under the age of 18, foreigners, patients with incomplete data were excluded from this study (Fig. 1). Age, gender, presence of intracranial hemorrhage, type, and GCS in ICU were recorded in those 78 patients. The worst data in the first 24 hours and the APACHE II and INCNS scores were calculated. “Swallowing function” parameter in the INCNS score was not scored because of being not evaluated in any patient. Survival – death status of the patients from the intensive care unit was noted.

intensive care unit of Muğla Sıtkı Koçman University Training and Research Hospital during October 2017–July 2019, n=97

Foreigner, n=4 Age <18 years, n=8 Missing baseline data, n=7

Missing data for INCNS; • Corneal reflex, n=4 • Total bilirubin, n=3

Study Population, n=78

Figure 1. Flow chart displaying selective and exclusive process of patients with severe traumatic brain injury in the current study.

894

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software version 23.0. Continuous variables were expressed as mean±SD, median (interquartile range, IQR) and categorical variables were expressed as percentages. Continuous variables were analysed using Student’s t-test for normally distributed variables, and Mann-Whitney U test for non-normally distributed variables. Categorical variables were analysed using Pearson’s Chi-Square test analysis and Fisher’s exact tests, when appropriate. In all tests, a P-value below 0.05 was considered statistically significant. The receiver operating characteristics curve (ROC) analysis was used to determine the predictive power of APACHE II and INCNS. When a significant cut-off value was observed, the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were presented. While evaluating the area under the curve, a 5% type-I error level was used to accept a statistically significant predictive value of the test variables. Calibration of the prognostic models-defined as the accuracy of the estimated mortality rate-was assessed using the Hosmer-Lemeshow goodness-of-fit test, standardized mortality rate and calibration curves. For the multivariate analysis, the possible factors identified with univariate analyses were further entered into the logistic regression analysis to determine independent predictors of mortality. Hosmer-Lemeshow goodness of fit statistics was used to assess model fit. A 5% type-I error level was used to infer statistical significance. PASS (2008) was used in power calculations. Post power levels for APACHE II and INCNS were calculated by referencing Table 4–5 statistical results. The AUC value of APACHE II is 0.797±0.049 and the AUC value of INCNS is 0.847±0.050 and the standard AUC value to be tested is 0.5 and the power level calculated for n=78 (27 Death, 51 Survival) is 99.44% for APACHE II and 99.99% for INCNS.

RESULTS

Patients with TBI treated in the

Criteria of Excluding

Statistical Analyses

A total of 78 patients met the enrollment criteria of this study. The mean age of the patients was 47.11±17.07 years. Of these, 45 (57.7%) were males and 33 (42.3%) were females. The mean APACHE II and INCNS scores were 23.85± 9.44 and 14.43±8.75, respectively (Table 2). The APACHE II and INCNS scores were significantly higher in patients who died (p<0.001). Table 3 shows the distribution of APACHE II and INCNS scores between death and survival. The diagnosis of TBI included subarachnoid haemorrhage (n=21), subdural hematoma (n=14), concessional haemorrhage (n=20), epidural hematoma (n=17), brain edema (n=6). The overall mortality was 34.6% (27/78). There was a statistically significant difference between APACHE II and INCNS scores according to mortality Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Temperature (axillary, °C)

Albumin (g/L)

Awareness

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Unilateral/ bilateral muscle

Verbal response

Motor response

Water swallow test I–II

Swallowing function

Respiration

Not intubated, ≤11/≥25

Water swallow test III–IV/unable to assess

Localizing to/with- drawal from pain

strength scores of 2–3

Unilateral/bilateral muscle

Confused/inappropriate speech

–

question or commanda

Confused response to

Eye-opening to verbal command

25–34.9

≤35.9, 38.5–40

2.9–3.9, 10.1–25.0

Points

Breathes above ventilator rate

–

Flexing/extending to pain

scores ≤1

Unilateral muscle strength

Incomprehensible speech/none

Unilateral slow/ absent

Non-reflex movements

Eye-opening to pain

≤24.9

≥40.1

≤2.8, ≥25.1

Heart rate

SBP (mmHg)

Blood glucose (mmol/L)

Serum sodium (mmol/L)

Serum potassium (mmol/L)

Serum creatinine (μmol/L)

Total bilirubin (μmol/L)

≤34.1

44–132

3.5–5.5

130–150

3.9–11.1

90–140

60–100

≤44

34.2–102.5

≤43, 133–171

2.5–3.4, 5.6–6.9

120–129, 151–159

2.2–3.8, 11.2–19.3

70–89, 141–199

40–59, 101–149

45~64

≥102.6

≥172

≤2.4, ≥7.0

≤119, ≥160

≤2.1, ≥19.4

≤69, ≥200

≤39, ≥150

65~74

–

≥75

apnea

Breathes at ventilatorrate/

–

None

scores ≤1

Bilateral muscle strength

–

Bilateral slow/absent

None

–

SBP: Systolic blood pressure; WBC: White blood cell. aThe examiner may ask a question about the patient’s name or command the patient to move eyeballs and/or hands, if appropriate. bInclude evidence of visual pursuit or non-contingent behaviors. cEither the muscle strength test or motor response to a painful stimulus is performed in each patient.

Age (y)

Systemic condition

Not intubated, 12~24

Obeying to command

strength scores ≥4

Accurate speech

Corneal reflex

Bilateral sensitive

Pupillary light reflex

Bilateral sensitive

question or commanda

Correct response to

Spontaneous eye opening

≥35

36–38.4

4–10

Neurologic function

Arousal

Consciousness

Nutrition

WBC (109/L)

Inflammation

Variable

Table 1. INCNS scoring system[8]

Gürsoy et al. APACHE II or INCNS to predict mortality in traumatic brain injury

895

GĂźrsoy et al. APACHE II or INCNS to predict mortality in traumatic brain injury

(p<0.001). We, therefore, decided to calculate cut-off points for APACHE II and INCNS scores according to mortality by receiver operating characteristic analysis. Area under the curve was 0.797 with 0.049 standard error for APACHE II and 0.847 with 0.050 standard error for INCNS (Fig. 2). The INCNS score system showed significantly higher AUROCs compared to the APACHE II. Results for APACHE II score were the cut-off point of 24.5, the sensitivity of 74.1%, the specificity of 72.5%, the posiTable 2. Patient demographic characteristics and results Variables Mean/Frequency Gender, n (%)

Female

33 (57.7)

Male

45 (42.3)

Age, mean (SD)

tive predictive value of 74.1% and negative predictive value of 72.5%. Results for INCNS score were the cut-off point of 17.5, the sensitivity of 81.5%, the specificity of 82.4%, positive predictive value of 81.5% and a negative predictive value of 78.6% (Table 4 and Table 5). Both scoring systems generated Hosmer-Lemeshow goodness-of-fit statistics test P-values >0.05, with INCNS (H-L statistics=6.72 p=0.956) having a better fit than APACHE II (H-L statistics=3.35, p=0.356). According to logistic regression results, INCNS and APACHE II were found to be statistically significant in predicting mortality, while the INCNS score shows stronger performance (p<0.001 and p<0.05, respectively). When the INCNS score increases, mortality increases by 0.832 times, while APACHE II increases mortality by 0.873 times (Table 6).

47.11 (17.07)

ROC Curve

APACHE-II

Mean (SD)

Median

23.85 (9.44)

1.0

16.25

Minimum

Maximum

0.8

Mean (SD)

14.43 (8.75)

Median

13.25

Minimum

Maximum

Sensitivity

INCNS 0.6

0.4

GCS

Mean (SD)

Median

8.02 (4.31)

Minimum

Maximum

0.2

APACHE II: Acute Physiology and Chronic Health Evaluation II; INCNS: Infection Nutrition Consciousness Neurologic Function, Systemic Condition; GCS: Glasgow Coma Scale; SD: Standard deviation.

0.0

.00

0.2

0.4

0.6

0.8

1.0

1 - Specificity

Figure 2. Receiver operating characteristic curves displaying predictive value of INCNS and APCHE II score for traumatic brain injury.

Table 3. Distribution of the APACHE II and INCNS scores between death and survival

Overall (n=78)

Survival (n=51)

Death (n=27)

p-value

<0.001

APACHE

Mean (SD)

23.85 (9.44)

20.49 (8.19)

30.22 (8.51)

Minimum

Maximum INCNS

Mean (SD)

14.43 (8.75)

10.70 (6.96)

21.48 (7.40)

Minimum

Maximum

<0.001

APACHE II: Acute Physiology and Chronic Health Evaluation II; INCNS: Infection Nutrition Consciousness Neurologic Function, Systemic Condition; SD: Standard deviation.

896

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Gürsoy et al. APACHE II or INCNS to predict mortality in traumatic brain injury

Table 4. ROC curves for the APACHE II and INCNS compared to mortality Significance of APACHE II ROC curve Area under the ROC curve (AUROC) Standard deviation 95% confidence interval p-value Significance of INCNS ROC curve Area under the ROC curve (AUROC) Standard deviation 95% confidence interval p-value

0.797 0.049 0.701 to 0.893 <0.001 0.847 0.050 0.749 to 0.944 <0.001

APACHE II: Acute Physiology and Chronic Health Evaluation II; INCNS: Infection Nutrition Consciousness Neurologic Function, Systemic Condition; ROC: The receiver operating characteristics curve.

Table 5. Diagnostic scanning tests for the APACHE II and INCNS Diagnostic scanning tests for APACHE II Cut-off Sensitivity Specificity PPV NPV p-value Diagnostic scanning tests for INCNS Cut-off Sensitivity Specificity PPV NPV p-value

24.5 74.1% 72.5% 73.1% 72.8% <0.001 17.5 81.5% 82.4% 81.5% 78.6% <0.001

APACHE II: Acute Physiology and Chronic Health Evaluation II; INCNS: Infection Nutrition Consciousness Neurologic Function, Systemic Condition; ROC: The receiver operating characteristics curve.

Table 6. Regression analysis of the significant individuals associated with mortality APACHE II INCNS

OR (95% CI)

p-values

0.873 (0.785–0.971) 0.832 (0.754–0.919)

0.012 <0.001

APACHE II: Acute Physiology and Chronic Health Evaluation II; INCNS: Infection Nutrition Consciousness Neurologic Function, Systemic Condition; OR: Odds ratio; CI: Confidence intervals.

DISCUSSION In this retrospective cohort study, the performance of the APACHE II and INCNS score in predicting the outcome of TBI patients was compared. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

The APACHE II scoring system was developed by Knaus in 1985 and is widely used worldwide to assess the status of critical patients in general intensive care units.[9] APACHE II scoring system consists of three parts: acute physiology score, age points and chronic health points.[3] The neurological status of the patients can only be evaluated using GCS; however, the verbal component of GCS cannot be tested in intubated patients. In addition, brain stem reflexes and respiratory pattern cannot be evaluated with GCS. Although this suggests that APACHE II may be insufficient in TBI, there are studies supporting the use of APACHE II in Neurological intensive care units.[5,9–12] Discrimination of the APACHE II for TBI was good in our study, as the AUROC that exceeded 0.80, which is the level considered to be satisfactory.[13] The INCNS score system was developed considering APACHE II and Simplified Acute Physiology Score II (SAPS II) scoring systems used for critical illness and the characteristics of the neurocritical disease.[8] Assessment of neurological function includes pupillary light reflex, cornea reflex, verbal and motor response, swallowing function and respiration parameters. Arousal and awareness evaluations are considered together for consciousness. A thorough examination of neurological function and consciousness provides a clearer understanding of the severity of TBI. Systemic evaluation is similar to that of APACHE II and SAPS II. In addition to APACHE II, nutritional status is also examined in INCNS. Thus, the severity of the disease can be calculated in TBI. Gao et al.[8] found that AUROC for INCNS was 0.788 (95% CI, 0.759–0.817). In our study, AUROC was found to 0.847 (0.749 to 0.944). The discrimination of a prognostic model is considered slightly good because AUROC is >0.8.[13] Pupil light reflex and corneal reflex are routine neurological assessments used in N-ICUs and are a convenient and simple approach to assess brainstem functions that play a role in maintaining basic functions, such as consciousness, breathing, heart rate and sleeping. INCNS differs from other scoring systems in that it contains parameters evaluating brainstem reflexes. Results from our study showed that the INCNS score had a significantly stronger predictive power in discriminative power, sensitivity and specificity than APACHE II. Therefore, the use of INCNS in N-ICUs may become common. Surgical interventions are frequently used in TBI.[14] Although there was no statistically significant difference, the mortality of patients undergoing surgical procedures increases compared to the patients treated conservatively.[12] Surgically treated patients are scored with the APACHE II scoring system while the presence of surgery is not evaluated with INCNS. This may be a limitation for INCNS. Considering the effects of genetic differences on systemic diseases and cultural differences on nutrition, prognostic models may have different consequences for societies. We aimed to investigate the prognostic performance of INCNS on the Turkish population by determining the exclusion criteria for foreign 897

Gürsoy et al. APACHE II or INCNS to predict mortality in traumatic brain injury

patients in this study. INCNS can be considered as a usable prognostic model for Turkish people based on the results. Our study has potential limitations. One limitation is the retrospective design of this study and the other limitation is the use of a single ICU data. These two situations limit the generalization of the use of our INCNS results in other ICUs. According to the results, the prognostic performance of INCNS and APACHE II scoring systems in the evaluation of TBI patients in our intensive care unit was shown to be good. The INCNS had higher discriminatory power than the APACHE II in predicting the mortality of TBI in the ICU. To verify INCNS’s prognostic performance, it is recommended to conduct prospective studies in N-ICUs and further elaborate the limitations of INCNS. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: G.G., C.G.; Design: G.G., C.G., S.G.D.; Supervision: G.G., S.G.D.; Resource: G.G., C.G.; Materials: C.G., Y.K.; Data: C.G., Y.K.; Analysis: C.G.; Literature search: G.G., C.G.; Writing: G.G., C.G., S.G.D.; Critical revision: G.G., S.G.D. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Yao S, Song J, Li S, Cao C, Fang L, Wang C, et al. Helsinki Computed Tomography Scoring System Can Independently Predict Long-Term Outcome in Traumatic Brain Injury. World Neurosurg 2017;101:528–33.

2. Peeters W, van den Brande R, Polinder S, Brazinova A, Steyerberg EW, et al. Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien) 2015;157:1683–96. 3. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818–29. 4. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81–4. 5. Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: The FOUR score. Ann Neurol 2005;58:585–93. 6. Moskowitz J, Quinn T, Khan MW, Shutter L, Goldberg R, Col N, et al. Should We Use the IMPACT-Model for the Outcome Prognostication of TBI Patients? A Qualitative Study Assessing Physicians’ Perceptions. MDM Policy Pract 2018;3:2381468318757987. 7. Talari HR, Fakharian E, Mousavi N, Abedzadeh-Kalahroudi M, Akbari H, Zoghi S. The Rotterdam Scoring System Can Be Used as an Independent Factor for Predicting Traumatic Brain Injury Outcomes. World Neurosurg 2016;87:195–9. 8. Gao Q, Yuan F, Yang XA, Zhu JW, Song L, Bi LJ, et al. Development and validation of a new score for predicting functional outcome of neurocritically ill patients: The INCNS score. CNS Neurosci Ther 2020;26:21–9. 9. Zou X, Li S, Fang M, Hu M, Bian Y, Ling J, et al. Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019. Crit Care Med 2020;48:e657–65. 10. Kim TK, Yoon JR. Comparison of the predictive power of the LODS and APACHE II scoring systems in a neurological intensive care unit. J Int Med Res 2012;40:777–86. 11. Nyam TE, Ao KH, Hung SY, Shen ML, Yu TC, Kuo JR. FOUR Score Predicts Early Outcome in Patients After Traumatic Brain Injury. Neurocrit Care 2017;26:225–31. 12. Dalgiç A, Ergüngör FM, Becan T, Elhan A, Okay Ö, Yüksel BC. The revised Acute Physiology and Chronic Health Evaluation System ( APACHE II ) is more effective than the Glasgow Coma Scale for prediction of mortality in head-injured patients with systemic. Turkish J Trauma & Emergency Surgery 2009;15:453–8. 13. Lemeshow S, Le Gall JR. Modeling the severity of illness of ICU patients. A systems update. JAMA 1994;272:1049–55. 14. Potapov AA, Krylov VV, Gavrilov AG, Kravchuk AD, Likhterman LB, Petrikov SS, et al. Guidelines for the management of severe traumatic brain injury. Part 3. Surgical management of severe traumatic brain injury (Options). Zh Vopr Neirokhir Im N N Burdenko 2016;80:93–101.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Travmatik beyin hasarında mortaliteyi tahmin etmede APACHE II mi INCNS mi?: Geriye dönük kohort çalışma Dr. Güven Gürsoy,1 Dr. Canan Gürsoy,2 Dr. Yağmur Kuşcu,3 Dr. Semra Gümüş Demirbilek3 1 2 3

Muğla Sıtkı Koçman Üniversitesi Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, Muğla Muğla Sıtkı Koçman Üniversitesi Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Yoğun Bakım, Muğla Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Muğla

AMAÇ: Mortaliteyi belirlemede akut fizyoloji ve kronik sağlık değerlendirme II (APACHE II) skorlama sistemi gibi birçok skorlama sistemi kullanılmasına rağmen travmatik beyin hasarına özgü değildir. INCNS travmatik beyin hasarı için Gao ve ark. tarafından geliştirilmiş yeni bir skorlama sistemidir. INCNS skorlama sistemi, enflamasyon, nutrisyon, bilinç, nörolojik fonksiyonlar ve sistemik durumu değerlendirmektedir. Çalışmamızın amacı travmatik beyin hasarında mortaliteyi tahmin etmede APACHE II ve INCNS’nin performansını değerlendirmektir. GEREÇ VE YÖNTEM: Travmatik beyin hasarı nedeniyle anestezi yoğun bakım ünitesinde tedavi edilen 78 hasta çalışmaya alındı. Hastaların tıbbi kayıtları geriye dönük olarak incelendi. On sekiz yaşından küçük olanlar, yabancılar, eksik verileri olan hastalar çalışma dışı bırakıldı. Hastaların ilk 24 saat içindeki verileri ile APACHE II ve INCNS skorları hesaplandı ve kayıt edildi. BULGULAR: Yetmiş sekiz hastanın 45’i (%57.7) erkek, 33’ü (%42.3) kadındır. Mortalite oranı %34.6 (27/78) olarak hesaplanmıştır. APACHE II ve INCNS skorlarının ortalaması sırasıyla 23.85±9.44 ve 14.43±8.75’dir. ROC eğrisi altında kalan alan APACHE II için 0.797, INCNS için 0.84’dür. TARTIŞMA: INCNS skorlama sistemi; yoğun bakım ünitesinde travmatik beyin hasarı mortalitesini belirlemede APACHE II skorlama sistemine göre daha güçlüdür ve Türk hasta popülasyonuna uygun olduğu söylenebilir. Anahtar sözcükler: Akut fizyoloji ve kronik sağlık değerlendirme II (APACHE II); INCNS skorlama sistemi; skorlama sistemi; travmatik beyin hasarı; yoğun bakım ünitesi mortalitesi. Ulus Travma Acil Cerrahi Derg 2020;26(6):893-898

898

doi: 10.14744/tjtes.2020.22654

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

High-pressure injection injuries to the upper extremity and the review of the literature Gökçe Yıldıran, M.D.,

Mustafa Sütçü, M.D.,

Osman Akdağ, M.D.,

Zekeriya Tosun, M.D.

Department of Plastic, Reconstrutive and Aesthetic Surgery, Division of Hand Surgery, Selçuk University Faculty of Medicine, Konya-Turkey

ABSTRACT BACKGROUND: High-pressure injection injuries of the hand are rare severe injuries. This study aimed to present a retrospective analysis of current and possible prognostic factors, treatment modalities and evaluation criteria. METHODS: Ten patients who had high-pressure injection injury to their upper extremity between 2005–2018 were included in this study. All patients were evaluated for the compartment syndrome; if exists fasciotomy and wide debridement were performed. After the first debridement, the second debridement was considered within the first 24 hours. RESULTS: In this study, 10 patients (mean age: 30) were evaluated retrospectively. The injected materials were the animal vaccine, thinner, oil, diesel, water, plastic and paint. Preoperative and postoperative mean WBC levels were 14.73 K/µL and 9.62 K/µL, respectively. Preoperative and postoperative mean neutrophil levels were 11.4 K/µL and 6.49 K/µL, respectively. CONCLUSION: Early and serial debridement and compartment syndrome evaluation are required. Despite these cautions, amputation may occur. Material, injection force and the time elapsed are the main determinants in prognosis. Aggressive debridement is required in high-pressure injection injuries. However, the adequacy of debridement should be evaluated because it is mostly impossible to completely clean the tissue from diesel or thinner. According to the experience of 10 cases in our series, when clinical and macroscopic debridement adequacy was observed, a decrease in WBC and neutrophil levels was observed simultaneously. For this reason, WBC and neutrophil levels may be an indicator of the adequacy of debridement, although these injuries are very rare, larger series are needed for this interpretation. Keywords: Hand; high-pressure; injection injury.

INTRODUCTION High-pressure injection injuries of the hand are rare, leading to severe necrosis or even amputations.[1,2] The most important feature of these injuries is that the examination findings do not show a severe hand injury, only one injection site can be detected on the skin, even the pain can be minimal, making it easier to neglect.[3] Historically, Rees described finger necrosis with high-pressure fuel oil injection in 1937.[1,3] The severity of the injury is determined by the force of the injection and the type of material. The pressure to pass through the skin is 100 psi and high-pressure injection injuries have caused injuries above this injection force.[1] The type of material also significantly affects the tissue damage. The presence of water,

oil, paint and organic solvents of the high-pressure injecting material is what determines both the fate of the hand and the reaction of the tissue and the extent of the damage in the tissue. Compartment syndrome, loss of function of the extremities and amputations are the results of high-pressure injection injuries. Therefore, good history, physical examination and management of treatment are critical. Following this, emergency intervention is essential and decompression and extensive surgical debridement are critical. Follow-up or waitand-see is not the treatment options. However, amputation rates of up to 48% have been reported, even if treated with an appropriate approach.[4] An injury with such serious con-

Cite this article as: Yıldıran G, Sütçü M, Akdağ O, Tosun Z. High-pressure injection injuries to the upper extremity and the review of the literature. Ulus Travma Acil Cerrahi Derg 2020;26:899-904. Address for correspondence: Gökçe Yıldıran, M.D. Selçuk Üniversitesi Tıp Fakültesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, El Cerrahisi Bilim Dalı, Konya, Turkey Tel: +90 332 - 606 05 05 E-mail: ggokceunal@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):899-904 DOI: 10.14744/tjtes.2020.26751 Submitted: 24.12.2019 Accepted: 02.03.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

899

Yıldıran et al. High-pressure injection injuries to the upper extremity and the review of the literature

sequences should be treated in hand surgery centers, as it is reported that one in every 600 traumas has injection injuries.[2] The clinical course and pathology of this type of injury are well known.[5] However, it is often presented in the literature as case reports.[6–15] In this study, we aimed to present a retrospective analysis of current and possible prognostic factors and treatment modalities of patients who applied to our hand surgery clinic.

MATERIALS AND METHODS Ten patients who had high-pressure injection injury to their upper extremity between 2005–2018 were included in our study. Patients were classified according to the patients’ age, gender, injected material type, hand laterality and injured hand part, duration between injection injury and patient application, treatment received and the result of treatment. Ethical approval for this study was obtained from Selcuk University ethical committee with the number of 2019/363.

Surgical Management All patients received tetanus and antibiotics prophylaxis and were evaluated clinically for the compartment syndrome; if it is diagnosed based on the physical examination, urgent fasciotomies were performed for the first step. In this surgery, wide debridement was also performed. All patients were operated urgently after their application. After the first debridement, the second debridement was considered within the first 24 hours. Wound dressings were changed twice a day. After serial debridement, the options for reconstruction (secondary wound healing, primary suturation, graft or flap surgeries) were evaluated.

RESULTS In this study, 10 patients were evaluated retrospectively, all of them were male and injury types were working accidents for all (Table 1). The mean age of patients was 30 (21–50). The injected materials were the animal vaccine (n=2), paint thinner (n=2), oil (n=2), diesel (n=1), water (n=1), plastic (n=1) and paint (n=1). Eight hands of injured hands were the nondominant hands. Only two patients were injured from their dominant hands. Affected extremity regions were the index finger (n=3), palm (n=2), thumb (n=1), 3rd finger (n=1), second webspace (n=1), forearm (n=1) and on the snuffbox (n=1) anatomically. Three patients were considered as compartment syndrome and underwent a fasciotomy surgery. All patients had serial debridement. Four patients were recovered with wound dressings and secondary intention, two patients had primary suturation, two patients’ defects were repaired with skin grafting and a local flap, two patients’ fingers were amputated, and defects were primarily repaired. The injected materials were painted thinner and diesel for these two amputated fingers. Preoperative and postoperative mean WBC levels were 14.73 K/µL and 9.62 K/µL, respectively. Preoperative and postoperative mean neutrophil levels were 11.4 K/µL and 6.49 K/µL, respectively.

Case Examples Case 1 – A 32-year-old male patient was admitted one hour after the high-pressure liquid plastic injection for the nondominant hand second webspace (Fig. 1). The patient was operated urgently, and surgical debridement was performed, during surgery, it was observed that the plastic material penetrated inside the skin did not spread inside the soft tissue, and the material was excised. The wound healed with secondary intention.

Approach to the management of high-pressure injection injuries was discussed with the review of the literature.

Case 2 – A 35-year-old male patient was admitted two hours after the high-pressure paint injection for the nondominant hand palm (Fig. 2). Considered as compartment syndrome,

(a)

(c)

(b)

(d)

Figure 1. (a) 32-year-old male, liquid plastic injection to the nondominant hand second web [Case no. 2]. (b) Incision and the appearance of the liquid plastic inside the tissue. (c) Liquid plastic is frozen in the tissue temperature. (d) The tissue defect was healed with secondary intention.

(a)

(b)

(c)

(d)

Figure 2. (a) 35-year-old male, high-pressure paint injection to the nondominant palm [Case no. 4]. (b) Compartment syndrome was detected and fasciotomy was performed. (c, d) Volar forearm and hand dorsum defects were closed with skin grafts.

900

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Yıldıran et al. High-pressure injection injuries to the upper extremity and the review of the literature

(a)

injury, the wounds were repaired with skin grafts and local flap. No complications or limitations in finger and hand movements were detected.

(b)

(c)

(d)

(e)

(f)

Case 3 – A 35-year-old male patient was admitted two hours after the high-pressure diesel injection for the nondominant 3rd finger (Fig. 3). 3rd finger was ischemic and there was no capillary refilling. Leucocyte was counted 15.9 K/ µL; neutrophil was 13 K/µL, CRP was 183 and procalcitonin was 0.012. The patient was operated urgently; however, extensive thrombosis that was not suitable for any revascularization along the proper palmar digital arteries and the common palmar digital artery was detected. After the first operation, WBC was counted as 11.5 K/µL; neutrophil was 8.5 K/µL, CRP reduced to 57.8, and procalcitonin was 0.05. Despite the dramatic reduction of WBC, neutrophil, CRP and procalcitonin levels, the finger was amputated 24 hours after the trauma.

DISCUSSION Figure 3. (a) 35-year-old male, high-pressure diesel injection to the nondominant 3rd finger [Case no. 5]. The finger was ischaemic. (b) Wide exposure was performed in order to debride all the necrotic tissues and an irrigation system was inserted. (c) Within a few hours, full thickness finger necrosis. (d) The secondary debridement was performed and total thrombosis in the digital artery was determined. (e) Wide exposure was performed, all the remained tissues were necrotic in the palmar region. Palmar necrosis was debrided and 3rd finger was amputated. (f) Early postoperative appearance after amputation.

urgently fasciotomies and wide debridement were performed. Because of the red color of the paint, it was possible to see the area where the paint spread. After the first debridement, it was determined that the WBC was reduced from 16 K/µL to 10.8 K/µL, the neutrophil levels were reduced from 12.9 K/µL to 6.88 K/µL. Due to the continuation of the necrosis, serial debridement was performed and two weeks after the

High-pressure injection injuries may occur with industrial tools and chemical injections. Thus, tissue damage may be mechanical, chemical or both. Mechanically, spreading may occur throughout the tendon sheath, deep spaces, and especially the neurovascular bundle. The direct effects of the pressure in the tissue were found by Kaufman et al.,[16] who showed that the material injected with high pressure, spread, especially along the neurovascular bundle, until the resistant tissue and after this resistance, the material has changed direction. Chemically, damage arises from the direct irritant effects of caustic materials.[17,18] Vascular occlusion after this initial injury leads to ischemia and tissue necrosis and destructive results, such as amputations. Subsequently, severe infections and severe tissue damage due to ischemia and necrosis occur. All injuries in this study were identified as work accidents. High-pressure injections are often used in industrial areas

Table 1. Demographic features and injury-related results No Age Gender Material 1

Male

Hand Effected Early treatment dominance region

Chicken vaccine Nondominant

Thumb

Serial debridements

Late term treament result

Healed with wound dressings

Male

Liquid plastic

Nondominant

Second web Serial debridements

Healed with wound dressings

Male

Thinner

Nondominant

Forearm

Serial debridements

Skin grafting

Male

Paint

Nondominant

Palm

Fasciotomy, serial debridements

Skin grafting and flap

Debridements, revascularization

Amputation

5 35 Male Diesel

Nondominant 3rd finger

Male

Oil

Dominant

Index

Fasciotomy, serial debridements

Healed with primary suturation

Male

Water

Nondominant

Snuffbox

Serial debridements

Healed with wound dressings

Male

Animal vaccine

Nondominant

Index

Fasciotomy, serial debridements

Healed with wound dressings

Male

Thinner

Dominant

Index

Serial debridements

Amputation

10 24

Male

Grease oil

Nondominant

Palm

Serial debridements

Healed with primary suturation

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

901

Yıldıran et al. High-pressure injection injuries to the upper extremity and the review of the literature

where water, oil, paint, various solvents and paint thinners, or even air need to be injected in various working areas; therefore, these injuries are often seen as work accidents. The most affected area is the index finger of the nondominant hand. According to one study, the most frequent localizations of high-pressure injection injuries in the upper extremity were the index finger, long finger, palm, thumb, ring finger, respectively.[1] In our study, the most affected area was the index finger of the nondominant hand, and it was observed that three of 10 patients were injured in this anatomical region. Devices that can perform high-pressure injection are held by the dominant hand as they require control. The nondominant index finger injury is an expected result after slipping or dropping of the material, which required high-pressure injection that is occasionally held in the nondominant hand. The degree of injury is related to the force of the injection and the type of material. While the spread of materials, such as plastic, paint and grease, is limited, the reaction gives very heavy damage to the tissue. Organic solvents are distributed in a wider area but cause a lighter reaction. In this study, the distribution of the material in tissue was found to be limited by the liquid plastic and grease. These patients showed rapid healing with wound dressings and primary suturing. However, the patient who was injured with paint thinner had no compartment syndrome and even a very limited area was affected, but the forearm defect in the patient had to be repaired by a skin graft. With these findings, it is possible to predict the degree of injury with the type of material injected. Another important form of injury is oil-based paints and industrial solvents. If the material type is oil-based paints and industrial solvents, their damage is more than water-based paints or grease damage. The rate of amputation with oilbased paints was reported as 50% in one study.[19] Amputation was not reported in water-based ones. In a review, the amputation rates of the injected material were compared and over 70% amputation rates were observed in diesel injuries. It was followed by paint thinner, oil, paint and undercoating. [18] In another study, the rate of amputation in high-pressure injection injuries with paint thinner was found to be 80% and 67% in diesel-induced cases, respectively, followed by paint, grease and hydraulic fluid.[1] In this study, amputated two fingers were amputated as a result of diesel and paint thinner injury. In these patients, vascular occlusion was detected in the early period with the injection of diesel and the injury with the paint thinner was applied at the fingertip with necrosis. It should be foreseen by the surgeon that amputation rates are very high in patients presenting with diesel and paint thinner injection injuries and the finger may not be saved despite serial and aggressive debridement. Although high-pressure injections are dangerous and destructive, air and water injections are more innocent than other materials. Amputation was not observed with air and water injections in Hogan et al.’s[18] study. In a similar literature, no amputation was reported in water and air injections.[20] 902

In such injuries, because the site of entry is a single point, a small perforation hole and relatively good surrounding tissue are determined. Therefore, it is easier to skip such injuries. However, the material that causes this minor wound will then cause extensive soft tissue injuries with persistent and severe pain. It is essential that a good story is taken in order not to miss them. In history, the location of the injury, the type of the injected material should be asked. A critical point in the history should be the severity of the pressure; otherwise, a high-pressure injection injury can be considered as a simple injection injury. The impacts of an industrial type pressure pump will be more devastating than the injector of the chicken vaccine. Industrial type working pressures can reach up to 10000 psi, but the skin can exceed 100 psi pressure. Amputation rates were found to be 43% and 19%, respectively, in the injuries occurring above and below 1000 psi.[1] Early diagnosis and aggressive treatment are critical as high-pressure injection injuries, amputations, or dysfunction of the extremity cause severe consequences. The approach to the high-pressure injection injuries in the emergency room includes tetanus prophylaxis, broad-spectrum antibiotherapy, wound site irrigation. Prophylactic antibiotics, such as third-generation cephalosporins, are recommended to reduce future infection.[17,18] Irrigation should be done using Ringer Lactate.[18] If the injected material is a radiopaque material, the material’s distribution area can be shown in the X-ray, so the proximal border of the spread material; thus, the extent of debridement can be determined. In physical examination, the neurovascular examination should be performed, and detailed anamnesis should be taken. A hand surgeon must be evaluated. One of the main determinants of the outcome of the injury is the time from the injury to the operation.[21] According to Stark et al.’s[22] study, if the time between injury and surgery is over 10 hours, amputation rates increase significantly. The best results are obtained with debridement in the first six hours.[17] The other important point in this study was that WBC levels were more than 12 K/µL (mean 14.73 K/µL) in the preoperative period despite the absence of any obvious clinical infection, and these WBC levels rapidly decreased to an average of 9.62 K/µL (normal intervals) with early aggressive debridement. Neutrophilia, which can be determined in bacterial infections, are also present in these patients preoperatively. In high-pressure infections, the neutrophil average is above 11 K/µL and decreases to 6 K/µL after the first debridement. Although there is no clinical appearance of neutrophilia, leukocytosis, infected content, lack of appearance, there is a reaction against this acute condition in the body. The WBC levels of the patients whose fingers were amputated were 15.9 K/ µL and 12.1 K/µL, respectively. Thus, WBC levels cannot be Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Yıldıran et al. High-pressure injection injuries to the upper extremity and the review of the literature

a prognostic factor for the high-pressure injection injuries. However, blood counts and infection markers could be used as a simple scale to monitor the effectiveness and adequacy of debridement because aggressive decreases in WBC and neutrophil levels were determined only by surgical debridement. The intervention should be performed under operating room conditions. General anesthesia or plexus blocks are preferred. No local anesthesia or digital block should be applied to the patient. In addition, the choice of tourniquet should be based on a pneumatic tourniquet rather than a material that can push the material to the proximal levels like Esmarch.[23] In the presence of compartment syndrome, fasciotomy should be performed, and revascularization should be performed in the presence of circulatory problems. Broad and aggressive debridement should be administered and all soft tissues in the area of injury should be explored. The affected tissues should be irrigated; if possible, the limb should be removed from the entire material and removed as far as possible. The second debridement should be performed within 24 hours following initial debridement, followed by continuous irrigations and serial debridement to remove any remaining material and necrotic tissues. Wound care is important until soft tissue edema is controlled. Therefore, delayed repairs are often preferred. Defects that arise from large tissue necrosis and opened fasciotomy can be repaired in various ways. In this study, defects in patients were repaired with primary suturing, graft or local flaps. Splinting and physiotherapy are complementary to treatment. If the amputation is performed despite the interventions, it should be taken care of not to have any chemical contamination on the other regions of the hand while amputation is being performed. The amputation decision should not be delayed or neglected; otherwise, it would be a loss of time with permanent loss of strength, loss of function and multiple procedures.[18] According to some authors, in air, water and vaccine injections, the rules of this solid surgical debridement treatment may be stretched and fasciotomy may be performed when compartment syndrome is suspected because air and water are not caustic, irritant or toxic, requiring extensive debridement; however, they should be closely monitored as they cause dissection inside the tissue.[17] Infection is rarely observed in high-pressure injection injuries. If there is a delay in treatment and a medium is emerging due to the presence of ischemic tissues, the probability of infection increases. In the case of infection, this is often seen as a combination of gram-positive and gram-negatives because necrotic tissue is a very good medium, in the case of infection, this is often seen as a combination of gram-positive and gram-negatives. Treatment of this possible infection is extensive and aggressive debridement and broad-spectrum antibiotics should be added to the treatment. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

High-pressure injection injuries are a surgical emergency and should be recognized in the emergency department and require hand surgeon evaluation. The injected material and the pressure are the main prognostic factors that predict the amputation. The early surgical debridement, which is an important prognostic factor and under the control of the surgeon, will provide the best outcomes. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: G.Y.; Design: G.Y.; Supervision: Z.T.; Resource: M.S.; Materials: G.Y., O.A.; Data: G.Y., M.S.; Analysis: G.Y., Z.T.; Literature search: G.Y., M.S., O.A.; Writing: G.Y.; Critical revision: Z.T. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Cannon TA. High-pressure Injection Injuries of the Hand. Orthop Clin North Am 2016;47:617–24. 2. Reiner MM, Khoury WE, Mackel A, Ehredt DJ, Razzante MC. Reconstruction After Osteomyelitis of the Midfoot From High-Pressure Washer Injury. J Foot Ankle Surg 2017;56:1305–11. 3. Rosenwasser MP, Wei DH. High-pressure injection injuries to the hand. J Am Acad Orthop Surg 2014;22:38–45. 4. Saraf S. High-pressure injection injury of the finger. Indian J Orthop 2012;46:725–7. 5. Bekler H, Gokce A, Beyzadeoglu T, Parmaksizoglu F. The surgical treatment and outcomes of high-pressure injection injuries of the hand. J Hand Surg Eur Vol 2007;32:394–9. 6. Kelpin JP, Fahrenkopf MP, Van Pelt AE. Treatment of an Uncommon High-Pressure Orbital Injection Injury. J Craniofac Surg 2018;29:1829–31. 7. Sarwar U, Javed M, Rahman S, Wright TC. Digital high-pressure injection injury: the importance of early recognition and treatment. BMJ Case Rep 2014;2014:bcr2013203206. 8. Foran I, Oak NR, Meunier MJ. High-Pressure Injection Injury Caused by Electronic Cigarette Explosion: A Case Report. JBJS Case Connect 2017;7:e36. 9. Mushtaq J, Walker A, Hunter B. Under pressure: progressively enlarging facial mass following high-pressure paint injection injury. BMJ Case Rep 2016;2016:bcr2015212817. 10. Mauzo SH, Swaby MG, Covinsky MH. Tumefactive foreign body giant cell reaction following high-pressure paint injection injury: A case report and review of literature. J Cutan Pathol 2017;44:474–6. 11. Ryan AT, Johnstone BR. High-pressure injection injury: benign appearance belies potentially devastating consequences. Med J Aust 2017;206:477. 12. Zhang YT, Xue JH. High-Pressure Water Swelling Sealant Injection Injury to the Hand: a Case Report and Review of the Literature. Indian J Surg 2015;77:508–11. 13. McCarthy J, Trigger C. High-pressure injection injury with molten aluminum. West J Emerg Med 2014;15:120–1. 14. Collins M, McGauvran A, Elhassan B. High-pressure injection injury of the hand: peculiar MRI features and treatment implications. Skeletal Ra-

903

Yıldıran et al. High-pressure injection injuries to the upper extremity and the review of the literature diol 2019;48:295–9. 15. Noronha PA, Lomelino RO, Dinoá V, Marchiori E. Synovitis of the knee following a high-pressure injection injury with hydraulic oil. Skeletal Radiol 2018;47:1701–4. 16. Kaufman HD. The anatomy of experimentally produced high-pressure injection injuries of the hand. Br J Surg 1968;55:340–4.

MV. Culture results and amputation rates in high-pressure paint gun injuries of the hand. Orthopedics 2001;24:587–9. 20. Canter HI, Vargel I, Güçer T. Subcutaneous emphysema of hand and forearm after high-pressure injection of air during scuba diving. Ann Plast Surg 2000;45:337–8.

17. Amsdell SL, Hammert WC. High-pressure injection injuries in the hand: current treatment concepts. Plast Reconstr Surg 2013;132:586e–91e.

21. Christodoulou L, Melikyan EY, Woodbridge S, Burke FD. Functional outcome of high-pressure injection injuries of the hand. J Trauma 2001;50:717–20.

18. Hogan CJ, Ruland RT. High-pressure injection injuries to the upper extremity: a review of the literature. J Orthop Trauma 2006;20:503–11.

22. Stark HH, Ashworth CR, Boyes JH. Paint-gun injuries of the hand. J Bone Joint Surg Am 1967;49:637–47.

19. Mirzayan R, Schnall SB, Chon JH, Holtom PD, Patzakis MJ, Stevanovic

23. Booth CM. High pressure paint gun injuries. Br Med J 1977;2:1333–5.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Üst ekstremitenin yüksek basınçlı enjeksiyon yaralanmaları ve literatürün gözden geçirilmesi Dr. Gökçe Yıldıran, Dr. Mustafa Sütçü, Dr. Osman Akdağ, Dr. Zekeriya Tosun Selçuk Üniversitesi Tıp Fakültesi, Plastik, Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, El Cerrahisi Bilim Dalı, Konya

AMAÇ: Elin yüksek basınçlı enjeksiyon yaralanmaları ciddi, nadir yaralanmalardır. Bu yazıda, mevcut ve olası prognostik faktörlerin, tedavi yöntemlerinin ve değerlendirme kriterlerinin geriye dönük analizi sunuldu. GEREÇ VE YÖNTEM: Çalışmaya 2005–2018 yılları arasında üst ekstremitede yüksek basınçlı enjeksiyon yaralanması olan 10 hasta alındı. Tüm hastalar kompartman sendromu açısından değerlendirildi; varsa fasiyotomi ve geniş debridman yapıldı. İlk debridmandan sonra ilk 24 saat içinde ikinci debridman yapıldı. BULGULAR: On hasta (ort. yaş 30) geriye dönük olarak değerlendirildi. Enjekte edilen materyaller hayvan aşısı, tiner, yağ, dizel, su, plastik ve boya olarak bulundu. Ameliyat öncesi ve sonrası ortalama WBC düzeyleri sırasıyla 14.73 K/µL ve 9.62 K/µL idi. Ameliyat öncesi ve sonrası ortalama nötrofil düzeyleri sırasıyla 11.4 K/µL ve 6.49 K/µL idi. TARTIŞMA: Erken ve seri debridmanlar ve kompartman sendromu değerlendirmesi gereklidir. Tüm önlemlere rağmen amputasyon ile sonuçlanabilir. Malzeme, enjeksiyon kuvveti ve geçen süre prognozdaki ana belirleyicilerdir. Yüksek basınçlı enjeksiyon yaralanmalarında agresif debridman gereklidir. Ancak, debridmanın yeterliliği değerlendirilmelidir çünkü dokuyu dizel veya tiner gibi materyallerden tamamen temizlemek imkansızdır. On olguluk çalışmadan edindiğimiz tecrübeye göre klinik ve makroskobik olarak debridman yeterliliği gözlendiğinde eşzamanlı olarak WBC ve nötrofil seviyelerinin de düştüğü belirlenmiştir. Bu nedenle WBC ve nötrofil seviyeleri debridmanın yeterliliği için bir indikatör olabilir, ne var ki bu yaralanmalar çok nadir yaralanmalar olsa da bu yorumu yapabilmek için daha geniş çalışmalara ihtiyaç vardır. Anahtar sözcükler: El; enjeksiyon yaralanması; yüksek basınç. Ulus Travma Acil Cerrahi Derg 2020;26(6):899-904

904

doi: 10.14744/tjtes.2020.26751

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

The association between injury severity and psychological morbidity, hand function, and return to work in traumatic hand injury with major nerve involvement: A one-year follow-up study Nihal Tezel, M.D.,

Aslı Can, M.D.

Department of Physical Medicine and Rehabilitation, University of Health Sciences Dışkapı Yıldırım Beyazıt Training and Research Hospital Ankara-Turkey

ABSTRACT BACKGROUND: We aimed to investigate the association between the severity of the injury and psychological morbidities, hand functions, and return to work (RTW) in traumatic hand injury (THI) with major nerve involvement. METHODS: Thirty-two patients had THI with major nerve involvement were enrolled in this study. The demographic and clinical characteristics of the patients were recorded after the injury. The severity of the injury was evaluated using the modified Hand Injury Severity Score (MHISS). The Disabilities of the Arm, Shoulder, and Hand (Q-DASH) score and Duruöz Hand Index (DHI) were used to assess the hand function. Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Impact of Event Scale-Revised (IES) were performed to assess psychological morbidity. These assessments were performed after injury and at the end of the first year. Time to RTW was recorded in the first year after the injury. Jamar Hand Dynamometer and pinch meter were used for the measurement of hand and finger grip strength at the end of the first year. RESULTS: There were significant improvements in IES-R, BDI, BAI, Q-DASH, and DHI scores at the end of the first year compared with baseline scores. We found a significant correlation between MHISS and time of RTW, Q-DASH, and pinch strengths. We found no significant correlation between MHISS and IES-R, BDI, BAI, and grip strength. CONCLUSION: The severity of the injury is significantly associated with hand functions, pinch strengths, and RTW in THIs with major nerve involvement. The findings showed that there was no association between the severity of the injury and psychological morbidities in the present study. Keywords: Hand injury; injury severity score; psychological morbidity.

INTRODUCTION Traumatic hand injuries (THIs) are common injuries that affect approximately 10–30% of the global population. These injuries may lead to limited participation in daily living activities, delayed return to work (RTW), non-return to work, and consequently, severe financial and labor losses. This may also cause additional trauma, including psychological problems, such as depressive symptoms, anxiety, and posttraumatic stress disorder.[1]

The severity, type, and characteristics of the injured structures can affect the long-term outcomes and RTW.[2] Tendons, bones, vessels, or nerves in the hand may be damaged by traumatic injuries.[3] Major nerve injuries (median and/or ulnar nerves) are generally related to poor outcomes.[4] The loss of motor and sensory functions after a major nerve injury may profoundly impact functioning and daily living activities.[5]

Cite this article as: Tezel N, Can A. The association between injury severity and psychological morbidity, hand function, and return to work in traumatic hand injury with major nerve involvement: A one-year follow-up study. Ulus Travma Acil Cerrahi Derg 2020;26:905-910. Address for correspondence: Nihal Tezel, M.D. SBÜ Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Fiziksel Tıp ve Rehabilitasyon Kliniği, Ankara, Turkey Tel: +90 312 - 596 29 93 E-mail: nihaltezel@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):905-910 DOI: 10.14744/tjtes.2020.39472 Submitted: 04.10.2019 Accepted: 13.08.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

905

Tezel et al. The association between injury severity and psychological morbidity, hand function, and RTW in THI with major nerve involvement

Previous studies have focused on the relationship between the severity of upper extremity traumas, functional disability, and RTW.[2,6,7] On the other hand, the psychological status of the patients may also be affected by the severity of THIs. To our knowledge, in the literature, there is no study investigating the relationship between the severity of the injury and psychological morbidity in THI with major nerve involvement. The present study uniquely investigated the association between the severity of the injury and psychological morbidities, hand functions, and RTW in THI with major nerve involvement. We also aimed to investigate the long-term effects of severity of THI on psychological status, hand functions, and RTW.

MATERIALS AND METHODS Fifty patients who had THI with major nerve involvement were assessed for eligibility in the study between September 2016 and September 2019. Thirty-two patients were enrolled in this study based on the following inclusion and exclusion criteria. Inclusion criteria were as follows: (i) being over 18 years old; (ii) unilateral traumatic hand injury with median nerve and/or ulnar nerve involvement; (iii) intact hand functions before injury. Exclusion criteria were as follows: (i) previous severe upper extremity injuries; (ii) bilateral hand injuries; (iii) amputations; (iv) additional rheumatologic disorders; (v) inability to understand or follow instructions. The study protocol was approved by the local Ethics Committee (approval date:18/06/19; approval number: 65/07). A written informed consent was obtained from each patient. This study was conducted in accordance with the principles of the Declaration of Helsinki.

Intervention The hand rehabilitation program was started after a 3-week immobilization period for all patients. The rehabilitation program was tailored to the patient’s individual needs and applied three days a week for 12 weeks in our outpatient clinic. All patients’ demographic characteristics, including age, gender, occupation, injured anatomical structures, and injured side (dominant/non-dominant), were recorded. Return to work after the injury, time of RTW, and return to previous work were recorded at 12 months after the injury. All evaluations were performed face to face with the patients.

Primary Outcome Measures The Modified Hand Injury Severity Score (MHISS) was used to assess the severity of forearm, wrist, and hand injuries based on information in patients’ folders. It evaluates the integument, bones, tendons, muscles, and neurovascular structures. A higher score indicates a more severe injury. Psychological morbidities were assessed using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and 906

the Impact of Event Scale-Revised (IES-R). Depressive symptoms and anxiety of the patients were assessed by BDI and BAI, respectively. Both inventories are 21-item self-administered questionnaires. Each item is scored between 0 and 3 points. Higher scores indicate a greater level of anxiety and depression. The Turkish validity and reliability of BDI have been performed by Hisli.[8] The Turkish validity and reliability of BAI has been performed by Ulusoy et al.[9] The IES-R is a 22-item self-report questionnaire that evaluates the degree of distress after traumatic events. Each item is scored on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The validity and reliability study of the Turkish version of IES-R was performed by Çorapçıoğlu et al.[10] Hand functions were evaluated using the Quick Disabilities of the Arm, Shoulder and Hand score (Q-DASH) and Duruöz Hand Index (DHI). Q-DASH is a self-report questionnaire that contains 11 items. Each item is scored from 1 to 5 points. High scores indicate a lower functional level. The validity and reliability of the Turkish version of Q-DASH was performed by Düger et al.[11] Duruöz Hand Index (DHI) is a self-report questionnaire that contains 18 items related to hand functions. Each item is scored from 0 (no difficulty) to 5 (impossible to do). The total score ranges from 0 to 90 with higher scores, indicating poorer hand functioning. It is a reliable and valid questionnaire to evaluate hand functions in patients with traumatic hand injuries.[12] All patients were assessed early after the injury (within three weeks) using the MHISS. The BDI, BAI, IES-R, Q-DASH, and DHI were performed within three weeks after a traumatic injury and at the end of the first year.

Secondary Outcome Measures Grip strength is one of the indicators of the functional use of the hand. It was measured using a Jamar hydraulic hand dynamometer. Lateral pinch, 2-point pinch, and 3-point pinch strengths were measured using a Jamar hydraulic pinch gauge (Bolingbrook, IL, USA). Patients were seated with shoulder adducted, elbow 90° flexed, and forearm and wrist in a neutral position. Patients were encouraged to press as firmly as possible. Three consecutive measurements were performed. The average of the measurements was recorded in kilograms (kg). We evaluated the strengths of both healthy hand and injured hand in all patients at the end of the 12 months.

Statistics The Kolmogorov-Smirnov test was used to evaluate the distribution of normality. We performed paired t-test for normally distributed data and Wilcoxon signed rank test for non-normally distributed data to compare the clinical characteristics. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Tezel et al. The association between injury severity and psychological morbidity, hand function, and RTW in THI with major nerve involvement

Descriptive data were expressed in %, mean±SD or median (min-max). Spearman’s rank correlation coefficients were used to evaluate the relation between the MHISS and time of RTW, baseline Q-DASH, baseline DHI, baseline BDI, baseline BAI, baseline IES-R, grip strength, and pinch strengths. Spearman’s rank correlation coefficients were accepted as follows: 0.81–1.0 as excellent, 0.61–0.80 very good, 0.41–0.60 good, 0.21-0.40 fair, and 0–0.20 poor.[13] SPSS version 17 (SPSS Inc., Chicago, IL, USA) was used for all statistical analyses. p-values less than .05 were accepted as statistically significant.

RESULTS In this study, 32 patients were included. Of these patients, 29 were male (90.6%) and three were female (9.4%). Their mean age was 33.9±13.3. At the time of injury, 25 (78.2%) were workers. Eight of the 25 patients (32%) returned to work after the injury. While seven of these patients (87.5%) returned to previous work, one patient (12.5%) changed the work the after injury. The mean time of RTW was 69.6±32.8 days. The mean score of the MHISS was 84.5±34.2. The demographic and baseline clinical characteristics of the patients have been shown in Table 1. Table 1. Demographic and baseline clinical characteristics of the patients Age (mean±SD)

33.9±13.3

Gender, n (%)

Male

Female

29 (90.6) 3 (9.4)

Occupation, n (%)

Worker

25 (78.2)

Student

3 (9.4)

Retired

2 (6.2)

Unemployment

2 (6.2)

Injured structures, n (%)

Nerve

4 (12.5)

Nerve+tendon

19 (59.3)

Nerve+tendon+vessel

9 (28.1)

Injured hand, n (%)

Dominant

18 (56.3)

Non-dominant

14 (43.7)

Return to work after injury, n (%)

Yes

8 (32)

17 (68)

At the end of the 12 months, there were significant improvements in the BAI, BDI, IES-R, Q-DASH, and DHI scores compared with baseline scores. Clinical parameters of the patients at baseline and 12-month follow-up are shown in Table 2. At the end of the 12 months, the mean grip strength of the injured hand was 46.8% of the intact hand, the mean of 2-point pinch strength was 38.1% of the intact hand, the mean of 3-point pinch strength was 41.2% of the intact hand, and the lateral pinch strength was 36.1% of the intact hand. The mean values of the hand strengths at the end of the 12 months are shown in Table 3. The Spearman’s correlation analysis revealed that there were significant good correlations between the MHISS and Q-DASH, lateral pinch strength and 2-point pinch strength (r=0.60, p =0.02; r=0.82, p=0.01; r=0.43, p=0.02; respectively). The MHISS was weakly, but significantly correlated with time of RTW and 3-point pinch strength (r=0.30, p=0.04 and r=0.39, p=0.03, respectively). However, we found no significant correlations between the MIHSS and IES-R, BAI, BDI, grip strength, and DHI (r=0.01, p=0.93; r=-0.07, p=0.71; r=0.04, p=0.79; r=0.25, p=0.02; r=0.16, p=0.37, respectively). Correlation of the MHISS with clinical characteristics of the patients is shown in Table 4. Table 2. Clinical parameters of the patients at baseline and 12-month follow-up [(mean±SD) or median (minmax)] Baseline 12-month Z,t follow-up

IES-R

40 (0–80)

12 (0–59)

-4.9 (Z)

<0.001*

BDI

11.5 (0–55)

3 (0–34)

-3.9 (Z)

<0.001*

BAI

10 (0–55)

2.5 (0–50)

-4.4 (Z)

<0.001*

Q-DASH

59.4±18.8

34.8±18.1

5.8 (t)

0.002*

DHI

48.1±23.9

30.2±20.4

11.5 (t)

<0.001*

BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; Q-DASH: Quick Disabilities of the Arm, Shoulder and Hand; DHI: Duruöz Hand Index; IES-R: Impact of Event Scale-Revised; SD: Standard deviation. *: Statistically significant difference.

Table 3. The mean hand strengths values at the end of the 12 months (mean±SD)

Intact hand

Injured hand

Return to previous work, n (%)

7 (87.5)

Grip strength (kg)

35.8±5.7

16.3±9.6

Time of return to work (day)

69.6±32.8 (15–100)

Lateral pinch strength (kg)

10.3±4.3

3.5±1.2

2-point pinch strength (kg)

10.1±2.9

3.6±1.5

84.5±34.2 (20–151)

3-point pinch strength (kg)

10±2.6

3.9±1.5

(mean±SD) (min-max) MHISS (mean±SD) (min-max)

MHISS: Modified Hand Injury Severity Score; SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

SD: Standard deviation.

907

Tezel et al. The association between injury severity and psychological morbidity, hand function, and RTW in THI with major nerve involvement

Table 4. Correlation of the MHISS scores with clinical characteristics of the patients Time of return to work

MHISS (r) 0.30*

IES-R

0.01

BAI

-0.07

BDI

-0.04

Q-DASH 0.60* DHI 0.16 Grip strength

0.25

Lateral pinch strength

0.82*

2-point pinch strength

0.43*

3-point pinch strength

0.39*

BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; DHI: Duruöz Hand Index; IES-R: Impact of Event Scale-Revised; MHISS: Modified Hand Injury Severity Score; Q-DASH: Quick Disabilities of the Arm, Shoulder and Hand, r: Spearman’s correlation coefficient. *: Statistically significant difference.

DISCUSSION Traumatic injuries may lead to trauma-related psychiatric disorders. Post-traumatic distress disorder, depression, and anxiety are the most common psychological morbidities following traumatic injuries.[14,15] Both severity and site of traumatic injuries may be related to psychological disorders after the traumatic injury.[16] To our knowledge, there is no study to evaluate the association between the severity of the injury and psychological morbidity in THIs with major nerve involvement. In this study, we evaluated the association between the severity of the injury and psychological morbidities, functioning, and RTW in THIs with major nerve involvement. The MHISS was designed to grade the severity of THIs and to predict the injury outcomes. The MHISS results can be categorized into four groups: a score of ≤ 20 indicates a mild THI; a score of 21–50 indicates a moderate THI, a score of 51–100 reflects a severe THI; and a score of ≥101 correlates with a significant THI.[17] The MHISS results in our study ranged from 20–151, with a mean value of 84.5. This result suggests that most of our patients had severe injury. The psychological effects of hand injuries are the most common in the first month following injury and begin to reduce significantly within 6–9 months. The effects may maintain even after 18 months.[18] O’Donnell et al. reported that prevalence rates of post-traumatic distress disorder, depression, and anxiety decreased at 12 months after the injury.[15] Similarly, we detected significant improvements in symptoms of anxiety, depression, and post-traumatic distress disorder in THI patients at the end of the 12 months compared with symptoms in the first three weeks. We also detected that hand functions (Q-DASH and DHI scores) improved significantly at the end of the 12 months compared with baseline 908

hand functions. Similar to our results, Dogu et al.[18] found a significant improvement in hand functions at 6–9 months after the hand injury. On the other hand, we detected that grip and pinch strengths of the injured hand remained under the uninjured hand strengths in 12 months after the injury. We did not assess injured hand strengths early after the injury because of 3-week immobilization splint usage. On the other hand, we assumed that hand strength tend to increase because a close association has been known between hand function and hand strength. Psychological disorders have a negative effect on general health status after THI. The most frequent types of psychopathology associated with hand trauma are posttraumatic distress disorder and depression. Approximately one-third of patients with THI has symptoms of these psychological disorders.[19] There are some studies to evaluate the psychological impacts of the hand injury.[18–20] Our study differed from previous studies in that we investigated the association between the severity of the injury and psychological morbidities in THI with major nerve involvement. In the present study, we found no correlation between the injury severity and symptoms of posttraumatic distress disorder, depression, and anxiety. This result can be attributed to the small sample size of the study and assessment tools have been used. Major nerve injuries of hand seem to delay RTW more than other injuries, such as tendon injuries and digital nerve injuries.[20,21] In the present study, only 32% of the patients returned to work within 12 months after injury. The mean time to RTW was detected to be 70 days. Similar to our results, Marom et al.[1] reported that the mean time to RTW was 94 days. Contrastly, Bruyns et al.[22] found that 59% of patients with nerve injury returned to work after injury and the meantime was approximately 220 days. Different results can be explained by different kinds of jobs and different characteristics of injury, such as additional injured structures and the severity of injuries. In our study, most of the patients had additional tendon and/or vessel injuries and most of them had a severe injury. The severity of the injury is the most important factor to RTW after hand injuries.[7] In the present study, we found that the severity of THI was positively correlated with the time of RTW. Consistent with our result, Lee et al.[7] reported that there was a significant relationship between the severity of the injury and the probability of RTW. Çakır et al.[2] also found a significant relationship between the severity of the injury and the time of RTW in patients with hand and forearm injuries. According to these results, patients with severe injuries were significantly less likely to RTW than patients with less severe injuries. The injury severity in the initial evaluation of patients is an important factor for determining the disability level. Çapkın et al.[6] reported a statistically significant correlation between Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Tezel et al. The association between injury severity and psychological morbidity, hand function, and RTW in THI with major nerve involvement

the MHISS and hand disability. Similarly, in the present study, the severity of THI was positively correlated with hand functions. We also detect a correlation between the severity of hand injury and pinch strengths, but no correlation was found with grip strength. In contrast to our results, Çakır et al.[2] found a significant correlation between the severity of hand injury and grip strength. They did not assess the pinch strengths of the patients. This study has several limitations. First, the small sample size is small and no power analysis was performed to calculate the study sample size. Larger sample size would have been more powerful. Second, we included not only patients with major nerve injury but also patients with tendon and/or vessel injuries.

Conclusion Severity of injury is significantly associated with hand functions, pinch strengths, and RTW in THIs with major nerve involvement. There was no association between severity of the injury and psychological morbidities in the present study. Future studies with a larger sample size are needed to confirm the relationship between the severity of the injury and psychological morbidities in THI with nerve involvement. Ethics Committee Approval: Turkish Ministry of Health, Health Sciences University, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Clinical Research Ethics Committee granted approval for this study (date: 18.06.2019, number: 65/07). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.C.; Design: A.C.; Supervision: N.T., A.C.; Resource: N.T., A.C.; Data: N.T., A.C.; Analysis: A.C.; Literature search: N.T., A.C.; Writing: N.T., A.C.; Critical revision: N.T., A.C. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Marom BS, Ratzon NZ, Carel RS, Sharabi M. Return-to-Work Barriers Among Manual Workers After Hand Injuries: 1-Year Follow-up Cohort Study. Arch Phys Med Rehabil 2019;100:422–32. 2. Çakır N, Özcan RH, Kitiş A, Büker N. Investigation of Relationship Between Severity of Injury, Return to Work, Impairment and Activity Participation in Hand and Forearm Injuries. Ulus Travma Acil Cerr Derg 2014;20:120–6. 3. Ozçelik B, Ertürer E, Mersa B, Purisa H, Sezer I, Tunçer S, et al. An alternative classification of occupational hand injuries based on etiologic mechanisms: the ECOHI classification. Ulus Travma Acil Cerrahi Derg 2012;18:49–54. 4. Bucknam RB, Dunn JC, Fernandez I, Nesti LJ, Gonzalez GA. Outcomes and return to work following complex nevre lacerations in the

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

volar forearm in an underserved Spanish-speaking population. JHSGO 2020;2:67–73. 5. Dahlin LB, Wiberg M. Nerve injuries of the upper extremity and hand. EFORT Open Rev 2017;2:158–70. 6. Çapkın S, Cavit A, Yılmaz K, Erdoğan E, Kaleli T. Associations between initial injury severity in acute hand, wrist or forearm injuries and disability ratings and time to return to work. Ulus Travma Acil Cerrahi Derg 2020;26:453–61. 7. Lee YY, Chang JH, Shieh SJ, Lee YC, Kuo LC, Lee YL. Association between the initial anatomical severity and opportunity of return to work in occupational hand injured patients. J Trauma 2010; 69(6):e88–93. 8. Hisli N. Beck Depresyon Envanterinin üniversite ögrencileri için geçerliligi ve güvenilirligi. J Psychol 1989;7:3–13. 9. Ulusoy M, Şahin NH, Erkmen H. Turkish Version of the Beck Anxiety Inventory. J Cognitive Psychotherapy 1998;12:163–72. 10. Çorapçıoğlu A, Yargıç İ, Geyran P, Kocabaşoğlu N. Olayların Etkisi Ölçeği (IES-R) Türkçe Versiyonunun Geçerlilik ve Güvenilirliği. New Symp J 2006;44:14–22. 11. Düger T, Yakut E, Öksüz Ç, Yörükan S, Bilgütay B, Ayhan Ç. Kol, omuz ve el sorunları (disabilities of the arm, shoulder and hand-DASH) anketi Türkçe uyarlamasının güvenirliği ve geçerliği. Fizyoter Rehabil 2006;17:99–107. 12. Erçalik T, Şahin F, Erçalik C, Doğu B, Dalgiç S, Kuran B. Psychometric characteristics of Duruoz Hand Index in patients with traumatic hand flexor tendon injuries. Disabil Rehabil 2011;33:1521–7. 13. Feise RJ, Michael Menke J. Functional rating index: a new valid and reliable instrument to measure the magnitude of clinical change in spinal conditions. Spine (Phila Pa 1976) 2001;26:78–87. 14. O’Donnell ML, Creamer MC, Parslow R, Elliott P, Holmes AC, Ellen S, et al. A predictive screening index for posttraumatic stress disorder and depression following traumatic injury. J Consult Clin Psychol 2008;76:923–32. 15. O’Donnell ML, Creamer M, Bryant RA, Schnyder U, Shalev A. Posttraumatic disorders following injury: an empirical and methodological review. Clin Psychol Rev 2003;23:587–603. 16. Baecher K, Kangas M, Taylor A, O’Donnell ML, Bryant RA, Silove D, et al. The role of site and severity of injury as predictors of mental health outcomes following traumatic injury. Stress Health 2018;34:545–51. 17. Campbell DA, Kay SP. The Hand Injury Severity Scoring System. J Hand Surg Br 1996;21:295–8. 18. Dogu B, Kuran B, Sirzai H, Sag S, Akkaya N, Sahin F. The relationship between hand function, depression, and the psychological impact of trauma in patients with traumatic hand injury. Int J Rehabil Res 2014;37:105–9. 19. Williams AE, Newman JT, Ozer K, Juarros A, Morgan SJ, Smith WR. Posttraumatic stress disorder and depression negatively impact general health status after hand injury. J Hand Surg Am 2009;34:515–22. 20. Opsteegh L, Reinders-Messelink HA, Schollier D, Groothoff JW, Postema K, Dijkstra PU, et al. Determinants of return to work in patients with hand disorders and hand injuries. J Occup Rehabil 2009;19:245–55. 21. Meiners PM, Coert JH, Robinson PH, Meek MF. Impairment and employment issues after nerve repair in the hand and forearm. Disabil Rehabil 2005;27:617–23. 22. Bruyns CN, Jaquet JB, Schreuders TA, Kalmijn S, Kuypers PD, Hovius SE. Predictors for return to work in patients with median and ulnar nerve injuries. J Hand Surg Am 2003;28:28–34.

909

Tezel et al. The association between injury severity and psychological morbidity, hand function, and RTW in THI with major nerve involvement

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Majör sinir tutulumu olan travmatik el yaralanmalarında yaralanma şiddeti ile psikolojik morbidite, el fonksiyonu ve işe dönüş arasındaki ilişki: Bir yıllık takip çalışması Dr. Nihal Tezel, Dr. Aslı Can Sağlık Bilimleri Üniversitesi Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Fiziksel Tıp ve Rehabilitasyon Kliniği, Ankara

AMAÇ: Travmatik el yaralanmalarında, majör sinir etkilenimi ile yaralanma şiddeti ile psikolojik morbidite, el fonksiyonları ve işe dönüş zamanı arasındaki ilişkiyi araştırmayı amaçladık. GEREÇ VE YÖNTEM: Çalışmaya majör sinir tutulumu olan 32 hasta alındı. Yaralanma sonrası hastaların demografik ve klinik özellikleri kaydedildi. Yaralanmanın şiddeti, El Yaralanması Ciddiyet Skoru (EYCS) kullanılarak değerlendirildi. El fonksiyonunu değerlendirmek için Kol, Omuz ve El (Q-DASH) skorları ve Duruöz El İndeksi (DEİ) kullanıldı. Psikolojik morbidite Beck Anksiyete Envanteri (BAE), Beck Depresyon Envanteri (BDE) ve Olay Etkisi Ölçeği-Revize (OEÖ-R) ile değerlendirildi. Bu değerlendirmeler yaralanmadan sonra ve ilk yılın sonunda yapıldı. İşe dönüş zamanı yaralanmadan sonraki ilk yılda kaydedildi. El ve parmak kavrama kuvvetinin ölçümü için Jamar El Dinamometresi ve pinçmetre kullanıldı. BULGULAR: Yıl sonunda OEÖ-R, BDE, BAE, Q-DASH ve DEİ skorlarında başlangıç skorlara göre önemli iyileşmeler oldu. EYCS ile işe dönüş zamanı, Q-DASH ve el ve parmak kuvvetleri arasında anlamlı bir korelasyon bulundu. ECYS ile OEÖ-R, BDE, BAE ve kavrama kuvveti arasında anlamlı bir ilişki bulunmadı. TARTIŞMA: Majör sinir tutulumu olan travmatik el yaralanmalarında yaralanmanın şiddeti el fonksiyonları, kavrama kuvvetleri ve işe dönüş zamanı ile önemli ölçüde ilişkilidir. Bu çalışmada, yaralanmanın şiddeti ile psikolojik morbidite arasında bir ilişki bulunmamıştır. Anahtar sözcükler: El yaralanması; kavrama kuvveti; yaralanma şiddeti skoru. Ulus Travma Acil Cerrahi Derg 2020;26(6):905-910

910

doi: 10.14744/tjtes.2020.39472

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds Gökhan İbrahim Öğünç, Ph.D.,1 Mustafa Tahir Özer, M.D.,2 Mehmet Eryılmaz, M.D.,2 Mustafa Mercan, M.Sc.3

Ali İhsan Uzar, M.D.,2

Gendarmerie and Coast Guard Academy, Institute of Security Sciences, Ankara-Turkey

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

Department of Forensics, General Command of Gendarmerie, Ankara-Turkey

ABSTRACT BACKGROUND: In this study, a 35 years old man was killed with the ricocheted shotgun pellets wounds from the asphalt road surface. The Public Prosecutor to define the ricochet point requested the ricocheted pellet pattern examination in two different ricochet distances. METHODS: The ten ricochet tests were performed for at 2 meters (point A) and 1 meter (point B) from the target, and the pellet distribution and pattern area were calculated using the gauss method. Then, the test and autopsy results were compared in the pellet number, calculated pellet pattern area and ricocheted angle. Furthermore, the similarity of the pellet number and the pellet pattern areas were examined using the two-tailed Mann-Whitney U test. RESULTS: In this study, 81 pellets recovered from the victim’s body and the distribution pattern of pellets area was 2134 cm2. At the ricochet point A, the average number of pellets on the target was 82.1 and the distribution pattern of pellets area was 2700 cm2. At the ricochet point B, the average number of pellets on the target was 132.6 and the distribution pattern of pellets area was 4928 cm2. According to the two-tailed Mann-Whitney U test, there was low-level similarity (p<0.05 level Sig. 0.023; z=-2.424) on the pellet pattern area between autopsy and the ricochet point A. However, as regards the pellet number on the target, there was a similarity (p<0.05 level Sig. 0.481; z=-0.808) between autopsy and the ricochet point A. CONCLUSION: Test results showed that the pellet ricochet occurred two meters from the victim. Keywords: Pellet ricochet; shooting reconstruction; shotgun wounds; wound ballistics.

INTRODUCTION The external and terminal ballistics issues of the shotgun ammunition are different from the rifling barrel firearms ammunition.[1] Owing to the weight and morphology of pellets, the flight and the target pattern of the birdshot and buckshot are the more influenced by the wind direction and velocity, air density, humidity, temperature, the wads’ design, intermediary target, and ricochet effects than rifling firearms bullets. Additionally, the choke constriction of the smooth barrel directly impacts the pellet distribution.[1,2]

Most of the projectiles can be deformed upon an impact with the unyielding and hard surface, but the lead pellets are more vulnerable to a collision than other projectiles. Furthermore, after ricochet, the shotgun pellets have a collision risk with each other and a billiard ball effect will occur.[3,4] In these circumstances, the pellet distribution increases and it is a wide and parallel pattern to the surface on the target in the close range.[1] The ricochet surface’s structure and specifications also will affect pellet behavior. Because of these independent

Cite this article as: Öğünç Gİ, Özer MT, Uzar Aİ, Eryılmaz M, Mercan M. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds. Ulus Travma Acil Cerrahi Derg 2020;26:911-919. Address for correspondence: Gökhan İbrahim Öğünç, Ph.D. İncek Şehit Savcı Mehmet Selim Kiraz Bulvarı, Beytepe, 06805 Çankaya, Ankara, Turkey Tel: +90 312 - 464 74 74 E-mail: gokhan.ogunc@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):911-919 DOI: 10.14744/tjtes.2020.76960 Submitted: 01.07.2019 Accepted: 14.01.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

911

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds

conditions, the calculation of the ricocheted pellet flight line and distribution pattern is a complicated and unpredictable forensic analysis.[5,6] As a general rule, to perform the precise shooting reconstruction and asses the range, the firearm used in the crime with the same brand and type ammunition should be used in the tests. In the ricocheted shotgun pellet reconstruction study, the test results are compared with the crime scene or the shotgun wound pattern. Using the same firearm and same brand/type ammunition and testing on the same or similar ricochet surface will be assisted in controlling the independent and unpredictable conditions.[7,8] In this study, a 35 years old man was killed by the ricocheted shotgun pellet wounds from the asphalt road surface. The crime scene examination unit found two suspicious deformation points on the asphalt surface as the pellet ricochet point. In order to define the pellet ricocheted point, the Public Prosecutor demanded to perform the ricocheted pellet pattern examination (shooting reconstruction) in these two different ricochet distance from the victim’s position (Ricocheted Point “A” is 2 meters from the victim’s position and Ricocheted Point “B” is 1 meter from the victim’s position and comparing the test patterns with the pellet entrance wounds pattern on the victim body. According to the crime scene examination report, the distance between the victim and muzzle was 2.6 meters.

from the suspect. For reaching the significant test results, additionally, 15 cartridges were taken from the Turkish National Police (TNP) Forensic Department ammunition collection. All these 15 cartridges were the same brand and type with the crime incident sample. The technical specifications of these cartridges are mentioned in Table 1.

Test Setup In the ricocheted pellet distribution test, the distance between the silhouette target and the shooting line was 2.6 meters. In this range, two ricocheted point was measured and marked on the asphalt surface. The first ricochet point, “A” was 2 meters from the silhouette target line and the second ricochet point “B” was 1 meter from the silhouette target line (Fig. 2). In the ricocheted pellet distribution tests,

In the autopsy, 81 pellets recovered from 179 cm length victim’s body. The distribution of the pellets was denser between the abdomen and femoral. According to the autopsy result, the death cause was multiple organ injuries.

MATERIALS AND METHODS The Location of the Pellet Entrance Wounds To obtain the correct locations of the shotgun pellets’ entrance wounds on the victim body, the standard photogrammetric techniques were used on the scaled external autopsy photographs. For correction, the lens distortion error of the external autopsy photographs, the “wrapping” process was applied.[9] Subsequently, the Cartesian coordinate system and scaled grid (mm) were placed on the scaled external autopsy photographs using the software. For these processes, Adobe Photoshop CS6 software was used. The entrance wounds’ coordinates recorded to the scaled body illustration for obtaining the pellet pattern on the victim’s body (Fig. 1).

Figure 1. The pellet pattern on the victim’s body.

Weapon and Ammunition The tests were performed with the same shotgun used in the crime incident. The shotgun was break action, #12/70 gauge, and single smooth barrel without any a choke constriction (Cylinder Choke). To perform the ricochet tests, the Public Prosecutor office provided 10 cartridges, which were seized 912

Figure 2. The ricocheted pellet test setup and ricocheted points (A and B).

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds

Table 1. The technical specifications of the test ammunition Cartridge Gauge

Cartridge Brand

Straling

Pellet Size / Type

#4 Birdshot / Lead

Pellet Weight

0.22 grams

Pellet Diameter

3.25mm

Number of Pellets in the Cartridges

144

Wad Type

B&PH21 Cup

Pellet Velocity

390±10m/s (Manufacture Spec.)

Table 2. The test setup specifications and ricochet points’ information 1st Ricochet Point (A) (2 meters from target)

Muzzle to Ricochet Point Distance

92 cm

Shooting Line to Ricochet Point Distance

60 cm

Muzzle Height

70 cm

Muzzle Angle

40°

Incident Angle

2nd Ricochet Point (B) (1 meter from target)

Muzzle to Ricochet Point Distance

183 cm

Shooting Line to Ricochet Point Distance

160 cm

Muzzle Height

70 cm

50°

Muzzle Angle

60°

Incident Angle

30°

the plywood panels (size: 200 cm×80 cm) covered with the silhouette target paper were used as a test target. To reach the significant test results, ten silhouette targets were used for each ricochet distance and only the one test fire made on each target. The fourth of the cartridges were provided from the suspect and the rest of the cartridges (six cartridges were the same brand and type with the crime incident sample) were from the TNP Forensic Department ammunition collection. After each test fire, the ricochet point moved 20 cm left; these proses were applied for all the ricochet distances (Table 2). There was not any information about the ricochet asphalt surface structure in the crime scene examination report. For that reason, the tests were performed on the concrete type asphalt (aggregate 93%–97% and bitumen 7%–3%), which is a common asphalt type in Turkey.[10]

Evaluation of the Test Results For assessing the possible ricochet point, the ricochet pattern tests’ results were evaluated in the four phases. In the first phase, the silhouette targets were separated into the Cartesian coordinate system regions. Subsequently, the number of pellets in each Cartesian coordinate system region was counted, and for determining the patterns (victim’s body and test target patterns), the average number of pellets was calculated. Then, the test results were compared with the autopsy report result. Because the real position of the victim was unknown, all of the pellet’s hits (not only the inner silhouette target border hits) on the target were taken account Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

in the ricochet tests. Additionally, the ricochet angles were calculated for each possible ricochet point and compared with the autopsy report result. In the second phase, the pellet pattern on the victim’s body and the ricocheted pellet test patterns were calculated with the Gauss Area Calculation (Shoelace Formula[11]) and the results were compared (Equation 1).

Equation 1. The shoelace equation. In the third phase, to obtain the overall distribution pattern, all the silhouette target patterns were overlapping and comparing with the anatomic distribution of the pattern on the victim’s body. In the last phase, to statistically examine the similarity of the test results with the autopsy results, the two-tailed Mann-Whitney U test was used on the IBM SPSS version 20 Software.

RESULTS As mentioned in the test setup, the ricocheted pellet distribution tests were performed on the two different ricochet points. It seemed in the overall evaluation of the test results that the pellet hits on all targets were in the scattered pattern. 913

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds

Figure 3. The first ricochet point “A” test results patterns and pellet distribution area.

The First Ricochet Point “A” Test Results (2 Meters from the Target) Ten test shots were made at the “A” ricochet distance (2 meters from the target). In these tests, the average number of pellets on the target was 82.1 (57% of the total pellet number in the cartridge); the distribution of the pellets was denser between the abdomen and femoral with 64.20% (Fig. 3) (Table 3); and the Gauss Method calculated the average area of the distribution pattern of pellets was 2700 cm2 (Table 4). The ricochet angles were calculated; the average of the lowest ricochet angle was 16.9°, and the average of the highest ricochet angle was 36.1° (Table 3) (Fig. 4).

The Second Ricochet Point “B” Test Results (1 Meter from the Target) Ten test shots were made at the “B” ricochet distance (1 meter from the target). In these tests, the average number of pellets on the target was 132.6 (92% of the total pellet number in the cartridge the distribution of the pellets was 914

denser between umbilical line and Crural with 83.54%, and the 16.46% of the pellets hit the between the chest and umbilical line area (Fig. 5) (Table 5); and the Gauss Method calculated the average area of the distribution pattern of pellets was 4928 cm2 (Table 6). The ricochet angles were calculated; the average of the lowest ricochet angle was 16.1o, and the average of the highest ricochet angle was 56.4° (Table 5) (Fig. 6). For the general evaluation of the ricocheted pellet distribution patterns, the distribution patterns of each ricochet point tests were overlapped and obtained the overall pattern (Fig. 7). Subsequently, these overlapping results compared with the anatomic distribution of the pattern on the victim’s body (Table 7). The overlapping of the ten test shots on the “A” ricochet point totally 821 pellets hit the target and the average pellet distribution area was 2772 cm2. The total pellet number on the target of the ten test shots on the “B” ricochet point was Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds Table 3. The “A” ricochet point test results Test Shots

Ricochet Angle

The Total Pellet Number on the Targe

1st Cartesian Coordinate System Region

2nd Cartesian Coordinate System Region

3rd Cartesian Coordinate System Region

4th Cartesian Coordinate System Region

Number Percentage Number Percentage Number Percentage Number Percentage of of Pellet of Pellet of Pellet of Pellet of of of Pellets Distribution Pellets Distribution Pellets Distribution Pellets Distribution

The The Lowest Highest Ricochet Ricochet Test #1

17.8°

42.7

21.43%

22.86%

17.14%

38.57%

Test #2

19.6°

38.9°

20.93%

17.44%

24.42%

37.21%

Test #3

18.9°

34.0°

27.63%

15.79%

18.42%

38.16%

Test #4

13.3°

37.5°

30.00%

17.78%

20.00%

25.56%

Test #5

13.7°

35.3°

24.47%

21.28%

19.15%

35.11%

Test #6

18.0°

35.1°

11.90%

15.48%

33.33%

39.29%

Test #7

18.0°

33.4°

14.46%

12.05%

46.99%

26.51%

Test #8

16.4°

33.4°

9.46%

13.51%

36.49%

40.54%

Test #9

15.3°

36.4°

17.72%

10.13%

43.04%

29.11%

Test #10

18.9°

34.5°

14.12%

12.94%

41.18%

31.76%

Average

16.9°

36.1°

82.1

15.9

19.21%

13.1

15.92%

24.6

30.01%

27.9

34.18%

Std. Dev.

2.22

2.98

7.38

6.26

6.84

3.63

4.02

9.38

11.47

4.20

5.54

Std. Err. Mean

0.7

0.92

2.33

1.98

2.16

1.14

1.27

2.96

3.62

1.32

1.75

Table 4. The Gauss method calculated the area of pellet distribution pattern of the ricochet point “A” tests Test Shots

Calculated Area by Gauss Method

Test Shots

Calculated Area by Gauss Method

Test #1

3254 cm2

Test #6

2384 cm2

Test #2

2802 cm

Test #7

2438 cm2

Test #3

2118 cm

Test #8

2118 cm2

Test #4

3380 cm

Test #9

2868 cm2

Test #5

3128 cm2

Test #10

2732 cm2

2 2 2

The Average of 10 Test Shots

2722 cm2

The Standard Deviation of 10 Test Shots

451.3 cm2

Standard Error of The Mean of 10 Test Shots

142.7 cm2

1326, and the average pellet distribution area was 4928 cm2. According to these results, the “A” ricochet point test results were similar to the autopsy results.

Concerning the calculated pellet distribution pattern area, there is not a similarity between the second ricochet point (B) test results and the autopsy examination result (p<0.05

To statistically examine the similarity of the ricochet pellet distribution pattern with the autopsy examination results (pellet pattern on the victim body), the two-tailed Mann-Whitney U test was applied to test pairs. Concerning the calculated pellet distribution pattern area, the similarity between the first ricochet point (A) test results and the autopsy examination result is low level (p<0.05 level Sig. 0.023; z=-2.424). However, as regards the pellet number on the target, there is a similarity (p<0.05 level Sig. 0.481; z=0.808) between the first ricochet point (A) test results and the autopsy examination results. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Figure 4. The first ricochet point “A” the averages lowest and highest pellet ricochet angles of 10 test tests.

915

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds

Figure 5. The second ricochet point “B” test results patterns and pellet distribution area.

level Sig. 0.000; z=-4.038), and also concerning the pellet number on the target, there is not a similarity (p<0.05 level

Sig. 0.000; z=-4.044) between the second ricochet point (B) test results and the autopsy examination result.

Table 5. The “B” ricochet point test results Test Shots

Ricochet Angle

The Total Pellet Number on the Targe

1st Cartesian Coordinate System Region

2nd Cartesian Coordinate System Region

3rd Cartesian Coordinate System Region

4th Cartesian Coordinate System Region

The The Lowest Highest Ricochet Ricochet Test #1

16.6°

57.9°

135

8.89%

5.93%

44.44%

40.74%

Test #2

16.4°

56.2°

136

7.35%

41.18%

44.12%

Test #3

16.6°

55.5°

132

8.33%

9.85%

43.94%

37.88%

Test #4

16.6°

57.0°

133

12.78%

15.04%

36.84%

35.34%

Test #5

16.4°

56.0°

130

11.54%

8.46%

40.77%

39.23%

Test #6

15.9°

57.2°

134

7.46%

5.97%

44.78%

41.79%

Test #7

16.0°

55.4°

130

5.38%

3.85%

53.85%

36.92%

Test #8

15.9°

56.3°

132

10.61%

6.82%

38.64%

43.94%

Test #9

15.9°

54.9°

129

8.53%

10.08%

38.76%

42.64%

Test #10

15.3°

58.5°

135

4.44%

5.93%

40.74%

48.89%

Average

16.1°

56.4°

132.6

11.3

8.53%

10.5

7.93%

56.2

42.39%

54.6

41.15%

Std. Dev.

0.42

1.14

2.41

3.40

2.59%

4.14

3.14%

6.25

4.85%

5.85

4.01%

Std. Err. Mean

0.13

0.36

0.76

1.07

0.82%

1.31

0.99%

1.97

1.53%

1.8

1.27%

916

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds

Figure 6. The second ricochet point “B” the average lowest and highest pellet ricochet angles of 10 test tests.

DISCUSSION According to the autopsy report, 81 pellets (56.2% of the total pellet number in the cartridge) recovered from the victim’s body. The location of pellet hits was determined from the scaled and “wrapping” process applied photos of the victim’s body. Afterward, the pellet entrance wounds and test fire pellet hit positions are placed/marked on the Cartesian coordinate system. The distribution of the 81 pellets was denser between the abdomen and femoral, with 61.73% at the victim’s body. The Gauss Method calculated area of the distribution pattern of pellets was 2134 cm2 (Fig. 1) on the victim’s body. The pellet ricochet tests were requested to perform in the two different distances (from target to muzzle 1 meter (rico-

Figure 7. The overlapping of the ten test shots of the “A” and “B” ricochet points with the autopsy examination result.

chet point “A”) and 2 meters (ricochet point “B”) (Fig. 2). Ten test fire was made for both distances, then the pellet number and pattern area on the target were calculated. For the pellet pattern area calculation, Gauss Method was used (Table 7). To see the overall pattern of pellet, the pellet patterns of the ten test fires were overlapping on the one target (Fig. 7). This process made for each distance. Subsequently, the test results were compared with the autopsy examination result. To statistically examine the similarity of the ricochet test results with the autopsy result, the two-tailed Mann-Whitney U test was used on the IBM SPSS version 20 Software.

Table 6. The Gauss method calculated the area of the pellet distribution pattern of the ricochet point “B” tests Test Shots

Calculated Area by Gauss Method

Test Shots

Calculated Area by Gauss Method

Test #1

4102 cm2

Test #6

5194 cm2

Test #2

4946 cm

Test #7

4205 cm2

Test #3

4844 cm2

Test #8

5572 cm2

Test #4

5243 cm

Test #9

4925 cm2

Test #5

5250 cm2

Test #10

4971 cm2

The Average of 10 Test Shots

4928 cm2

The Standard Deviation of 10 Test Shots

459.8 cm2

Standard Error of the Mean of 10 Test Shots

145.4 cm2

Table 7. The average pellet number and pattern area results Ricochet Points The Average 1st Cartesian 2nd Cartesian 3rd Cartesian 4th Cartesian Average Pellet Pellet Coordinate Coordinate Coordinate Coordinate Distribution Number on System Region System Region System Region System Region Pattern Area The Target Average Pellet Average Pellet Average Pellet Average Pellet (cm2) Distribution Distribution Distribution Distribution 1st Ricochet Point A (2m)

82.1

15.9 (19.21%)

13.1 (15.92%)

24.6 (30.02%)

27.9 (34.18)

2722

2nd Ricochet Point B (1m)

132.6

11.3 (8.53%)

10.5 (7.93%)

56.2 (42.39%)

54.6 (41.15%)

4928

16 (19.75%)

15 (18.52%)

22 (27.16)

28 (34.57%)

2134

Autopsy examination

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

917

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds

were distributed between the abdomen and femoral region. And some of the pellets individually hit to the chest and head. The average lowest ricochet angle was 16.9°, and the highest ricochet angle was 36.1° for the first ricochet point “A”.

Figure 8. If the ricochet point was “A”, the calculated lowest and highest pellet ricochet angle of the victim’s body.

Figure 9. If the ricochet point was “B”, the calculated lowest and highest pellet ricochet angle of the victim’s body.

In the test results, it seems that while the ricochet point approaches to the target, the number of pellets increases and a wider pattern occurs on the target, and the lower line of the pattern is descended to the surface. Because when the distance between ricochet point and target become closer, the more pellet is hit the target; vice versa the more pellets escape from the sides of the target and the center of pellet mass are ascending. In this context, each ricochet point test results were compared with the autopsy results: a. The pellet number on the victim body was 81, the pellet distribution pattern area was 2134 cm2, and the pellet ricochet angles to the victim body were calculated in lowest and highest angle for both suspected ricochet point. If the point “A” accepted as a pellet ricocheted point, the calculated lowest pellet ricochet angle was 18° and the highest ricochet angle was 35° (Fig. 8). On the other hand, when the point “B” was accepted as a pellet ricochet point, the calculated the lowest ricochet angle was 33°, and the highest ricochet angle was 54.5° (Fig. 9). b. The shooting reconstruction test for the first ricochet point “A” test, the pellets (average 82.1 pellets) hit the silhouette target with an irregular and wide pattern (average pattern area: 2722 cm2). The 64.20 percentage of the pellets 918

c. The shooting reconstruction test for the second ricochet point “B” test, the pellets (average 132.6 pellets), also hit the silhouette target with irregular and wider pattern (average pattern area: 4928 cm2) than the first ricochet point tests and the autopsy results. The distribution of the pellets was denser between theumbilical line and Crural with 83.54 percentage. The average lowest ricochet angle was 16.1°, and the highest ricochet angle was 56.4÷ for the first ricochet point (B). The difference between the 2nd ricochet point “B” test patterns and the autopsy examination pattern was illustrated in Figure 7. According to the two-tailed Mann-Whitney U tests, there is a similarity between the first ricochet point “A” test results and autopsy examination result concerning calculated pellet distribution pattern area (p<0.05 level Sig. 0.023; z=-2.424) and the pellet number on the silhouette target (p<0.05 level Sig. 0.481; z=-0.808). However, there is not a similarity between the second ricochet point “B” test results and autopsy examination result concerning calculated pellet distribution pattern area (p<0.05 level Sig. 0.000; z=-4.038) and the pellet number on the silhouette target (p<0.05 level Sig. 0.000; z=-4.044). Consequently, according to the shooting reconstruction study results (numbers of pellet hits, the calculated pellet pattern area and the angles of the pellet ricochets) and the crime scene examination and the autopsy reports, it is evaluated that the pellet ricocheted, which caused the victim’s death, occurred from the point “A” (2 meters far away from the victim’s position). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: G.İ.Ö.; Design: G.İ.Ö.; Supervision: G.İ.Ö.; Resource: G.İ.Ö.; Materials: G.İ.Ö.; Data: G.İ.Ö.; Analysis: G.İ.Ö., M.T.Ö., A.İ.U., M.E., M.M.; Literature search: G.İ.Ö.; Writing: G.İ.Ö., M.T.Ö.; Critical revision: M.E. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. DiMaio VJM. Gunshot Wounds. 3rd edition. Boca Raton, FL: CRC Press; 2016. 2. Rinker RA. Understanding Firearms Ballistics Basic to Advanced Ballistics. 6th edition. Clarksville, IN: Mulberry House Publishing; 2008. 3. Haag MG, Haag LC. Shooting Incident Reconstruction. 2nd edition. San Diego, CA: Academic Press; 2011. 4. Coe JI, Austin N. The effects of various intermediate targets on dispersion of shotgun patterns. Am J Forensic Med Pathol 1992;13:281—3.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Öğünç et al. The analysis and shooting reconstruction of the ricocheted shotgun pellet wounds 5. Hueske EF. Practical Analysis and Reconstruction of Shooting Incidents. 2nd edition. Boca Raton, FL: CRC Press; 2016. 6. Gardner RM, Bevel T. Practical Crime Scene Analysis and Reconstruction. Boca Raton, FL: CRC Press; 2009. 7. Mahoney PF, Ryan JM, Brooks AJ, Schwab CW. Ballistic Trauma A Practical Guide. 2nd edition. London: Springer; 2005. 8. Dodd MJ. Terminal Ballistics: A Text and Atlas of Gunshot Wounds. Boca Raton, FL: CRC Press; 2006.

9. Nordby JJ. Scientific Foundations of Crime Scene Reconstruction Introducing Method to Mayhem. 1stedition. Boca Raton, FL: CRC Press; 2013. 10. Republic of Turkey General Directorate of Highways. Technical Specification of Highway. Ankara; 2013. 11. Shoelace Formula. Available at: https://ipfs.io/ipfs/QmXoypizjW3WknFiJnKLwHCnL72vedxjQkDDP1mXWo6uco/wiki/Shoelace_formula.html. Accessed February 20, 2018.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Seken av tüfeği saçma tanesi yaralanmalarının analizi ve atışın yeniden yapılandırılması Dr. Gökhan İbrahim Öğünç,1 Dr. Mustafa Tahir Özer,2 Dr. Ali İhsan Uzar,2 Dr. Mehmet Eryılmaz,2 Dr. Mustafa Mercan3 1 2 3

Jandarma ve Sahil Güvenlik Akademisi, Güvenlik Bilimleri Enstitüsü, Ankara Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Ankara Jandarma Genel Komutanlığı, Kriminal Daire Başkanlığı, Ankara

AMAÇ: Bu çalışmada, asfalt yol yüzeyinden seken saçma tanelerinin 35 yaşındaki erkeğe isabet etmesi sonucunda ölüm olayı gerçekleşmiştir. Savcılık makamı, saçma tanelerinin sektiği noktanın tespit edilmesi için iki farklı sekme noktasından saçma tanesi dağılım kalıbı analizini talep etmiştir. GEREÇ VE YÖNTEM: Hedeften 2 metre (A noktası) ve 1 metre (B noktası) uzaklıkta bulunan iki sekme noktasına 10’ar adet test atışı yapılmıştır. Atışlar sonrasında hedefte oluşan saçma tanesi dağılım kalıplarının alanları Gauss metodu ile hesaplanmıştır. Ardından, test sonuçları ile otopsi sonuçları, hedefe isabet eden saçma tanesi sayısı, dağılım kalıbı alanları ve sekme açıları bakımından karşılaştırılmıştır. Ayrıca, hedefe isabet eden saçma sayısı ile saçma dağlım kalıbı alanlarının otopsi verileriyle olan benzerlikleri iki kuyruklu Mann-Whitney U testi ile incelenmiştir. BULGULAR: Kurbanın vücudundan 81 adet saçma tanesi elde edilmiştir ve saçma tanesi dağılım kalıbının alanı 2134 cm2’dir. A sekme noktasına yapılan atışlarda hedefteki ortalama saçma tanesi sayısı 82.1 ve saçma tanesi dağılım kalıbının alanı 2700 cm2’dir. B sekme noktasına yapılan atışlarda hedefteki ortalama saçma tanesi sayısı 132.6 ve saçma tanesi dağılım kalıbının alanı 4928 cm2’dir. İki kuyruklu Mann-Whitney U testi sonuçlarına göre A noktasından saçma tanelerinin dağılımı ile otopsi sonuçları arasında düşük seviyede (p<0.05 level Sig. 0.023; z=-2.424) benzerlik bulunmaktadır. Bununla beraber A noktasından seken saçma tanesi sayısı ile kurbanın vücudundan elde edilen saçma tanesi sayısı arasında benzerlik (p<0.05 level Sig. 0.481; z=-0.808) bulunmaktadır. TARTIŞMA: Test sonuçlarına göre saçma taneleri kurbana 2 metre mesafeden sekerek isabet etmiştir. Anahtar sözcükler: Atışın yeniden yapılandırılması; av tüfeği yaralanması; saçma tanesi sekmesi; yara balistiği. Ulus Travma Acil Cerrahi Derg 2020;26(6):911-919

doi: 10.14744/tjtes.2020.76960

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

919

ORIGIN A L A R T IC L E

Evaluation of the Nexus X-ray rules in blunt thorax trauma Ethem Acar, M.D.,1 Ahmet Demir, M.D.,1 Birdal Yıldırım, M.D.,1 Ömer Doğan Alataş, M.D.,1 Rabia Mihriban Kılınç, M.D.,2 Arife Zeybek, M.D.,3 Osman Özkaraca, M.D.4

Gökhan Kaya, M.D.,1

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

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

Department of Thoracic Surgery, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla-Turkey

Department of Computer Hardware, Muğla Sıtkı Koçman University Faculty of Technology, Muğla-Turkey

ABSTRACT BACKGROUND: There is still no agreed radiographic rule for the evaluation of blunt thoracic trauma. Emergency physicians want radiography according to their experience and examination findings. Various studies have been carried out on this subject and some of these studies have reached findings that can support the initial steps of the rules of radiography. One of them is the rule of Nexus thorax radiography rules. In this study, we aim to determine the accuracy of nexus thorax radiography rules. METHODS: Our study was a prospective cohort study performed in the emergency department of our University Hospital. In this study, 690 patients were evaluated. RESULTS: As a result of our study, we observed that patients were asked for more thoracic trauma because of chest pain, palpation tenderness in the thorax and sudden deceleration mechanism and pathology was found in approximately 25% of all imaging. The most common pathology we observed was rib fracture. Approximately 45% of the patients underwent thorax CT, and thorax CT was the most frequently requested for the detailed examination. When we evaluate the patients according to nexus thorax radiography rules, it was seen that the mechanism of sudden deceleration, intoxication and the disturbing, painful injury was more important than other parameters. The overall sensitivity and specificity of Nexus thorax radiographs were found to be 98% and 38%, respectively. CONCLUSION: In the evaluation of blunt thoracic trauma, the rules of nexus thorax radiography are considered useful concerning pathological detection. Keywords: Blunt thoracic trauma; emergency department; nexus rules.

INTRODUCTION Trauma is one of the most important causes of mortality and morbidity in adult patients. Thoracic, head, vertebral and abdominal traumas frequently result in death.[1–3] Currently, there are accepted imaging rules in abdominal and extremity trauma except head and cervical traumas.[4–7] For example, when evaluating head trauma, Glasgow coma score (GCS), as well as Canadian Brain Computed Tomography (CT) rules or New Orleans Brain CT rules, are used, and Nexus cer-

vical vertebra radiography rules are used when evaluating cervical traumas. However, there is still no clinically accepted radiographic rule in the evaluation of thoracic trauma. Physicians request radiography according to examination findings and their own experience. Various studies have been carried out on this subject and some of these studies have obtained results that can support the initial steps of the rules of radiography. One of these is the rule of Nexus thorax radiography. However, these rules have not been included in the guidelines yet, and further studies are needed[6,8] In our

Cite this article as: Acar E, Demir A, Yıldırım B, Kaya G, Alataş ÖD, Kılınç RM, et al. Evaluation of the Nexus X-ray rules in blunt thorax trauma. Ulus Travma Acil Cerrahi Derg 2020;26:920-926. Address for correspondence: Ethem Acar, M.D. Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Muğla, Turkey Tel: +90 252 - 212 75 27 E-mail: dr.ethemacar@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):920-926 DOI: 10.14744/tjtes.2020.55594 Submitted: 09.12.2019 Accepted: 11.02.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

920

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Acar et al. Evaluation of the NEXUS X-ray rules in blunt thorax trauma

study, we aim to determine the accuracy of nexus thorax radiography rules.

MATERIALS AND METHODS Our study is a prospective cohort study conducted in Mugla Sıtkı Kocman University Education and Research Hospital Department of Emergency. Ethics committee permission was obtained for this study. Patients who were admitted to the emergency department with blunt thoracic trauma between May 2018 and May 2019 were included in this study. Inclusion criteria were: 1) Patients over 18 years of age, (2) patients who applied to the emergency department within 24 hours after blunt trauma (3) were asked to perform thorax imaging. The exclusion criteria were: (1) Patients under the age of 18 (2) who did not want to take part in this study (3) who applied to the emergency department due to penetrating injury mechanism (4) who applied to our emergency department more than 24 hours after trauma (5) X-ray untreated or unreached patients.

Before this study, a form was constructed, including the criteria and additional criteria of the NEXUS chest radiography rule (Table 1). Emergency medicine specialists who participated in this study were informed about this study and the questioning of the criteria. Emergency physicians were asked to evaluate the trauma according to the patient examination findings and their own experience and to question the criteria in the postform. If the physicians underwent X-ray/CT in the presence of thoracic pathology, they were asked to mark the presence or absence of the causes in the above-mentioned form before the X-ray/CT evaluation (Table 1b). The form was also requested to mark whether there was a thoracic injury on the radiograph/CT. Hemothorax, pneumothorax, aortic and large vessel injury, rib fracture, diaphragmatic injury and pulmonary contusion were determined as thoracic injuries. In the form, the indications of thoracic CT request of the physicians were questioned (Table 1c). In addition, whether the patient had any additional injuries to the form, if any (1) did not require follow-up (2) whether there was a pathology

Table 1. Patient information collection form A. Nexus thorax radiography rules 1) Older than 60 years

Yes

2) Instantaneous deceleration mechanism (>20 ft [>6.0 m] or motor vehicle accident> 40 mph [>64 km/h])

Yes

3) Chest pain

Yes

4) Intoxication

Yes

5) Abnormal alertness / mental condition

Yes

6) Irritating painful injury

Yes

7) Sensitivity to chest wall palpation

Yes

B. Questioning why the doctors of our hospital have taken radiographs 1) Older than 60 years 2) Is there a sudden deceleration mechanism (>20 ft [>6.0 m] or motor ve-hicle accident >40 mph [>64 km/h])?

Yes

3) Do you have chest pain?

Yes

4) Do you have dyspnea ?

Yes

5) Hypoxia (sat ≤95)?

Yes

6) Do you have hemoptysis?

Yes

7) Is there any sensitivity to the thorax by palpation?

Yes

8) Is there a lesion in the thorax wall (such as a seat belt)?

Yes

9) Are there any additional injuries that would make the thoracic injury for-get?

Yes

10) Are there signs of abnormal lung auscultation?

Yes

11) Is there a disorder state of consciousness?

Yes

12) Is there any intoxication?

Yes

C. Questions that question why patients undergo CT 1) Although X-ray is normal, thoracic trauma remains suspected.

Yes

2) X-ray is not normal but for more detailed evaluation

Yes

3) Routine trauma for thoracic trauma

Yes

4) Because it is taken in addition to other CTs

Yes

CT: Computed Tomography.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

921

Acar et al. Evaluation of the NEXUS X-ray rules in blunt thorax trauma

that required inpatient follow-up (3) surgery, concerning thoracic injury, follow-up the treatment (1) (2) by inserting tube thoracostomy (3) thoracotomy (4) to determine whether it was performed by mechanical ventilation and asked to mark the form. The patient was discharged from the emergency department (1), admitted to the ward about the patient’s last condition (2) hospitalized in the intensive care unit (3) and died in the emergency department (4). Finally, the physician evaluating the patient was asked to state whether the patient had thoracic trauma or whether other trauma had priority in patients with multiple traumas. In deciding which priority area it concerns, it was asked to decide which of the treatments were more prioritized and that were more serious injuries. In case of any uncertainty at this point, the situation was decided together with the physician caring for the patient together with two associate professors (EA, BY) who were in the same study. To minimize the margin of error in this study, 10% of the patients were randomly selected. Radiographs of these patients were interpreted to the radiology and thoracic surgery specialists in the study independently. If radiological and thoracic surgeons were found to have significant differences between the first physician and the physician who checked the patient, all radiographs were planned to be evaluated by the radiologist and thoracic surgeon. In line with these data, each parameter in the study form was recorded in the SPSS program and statistical analyzes were performed.

model.[11] Sensitivity and specificity are calculated as in equality 1.[12] In this equation, TP is a true positive, TN is a true negative, FN is a false negative, and FP is a false positive.

RESULTS A total of 690 patients were included in this study. The mean age was 45.8±16.9 years. 284 (41.2%) were female, 385 (55.8%) were injured due to in-vehicle traffic accidents, Table 2. Demographic characteristics of the patients (n=690) Age (years), mean±SD

n (%) 45.8±16.9

Sex

Female

284 (41.2)

Male

406 (58.8)

Mechanism

Non-vehicle traffic accident

89 (12.9)

In-car traffic accident

385 (55.8)

Falling down

206 (29.9)

Assault

10 (1.4)

Application vitals

Systolic blood pressure ≤90 mmHg

52 (7.5)

Statistical Analysis

Systolic blood pressure ≥90 mmHg

638 (92.5)

All data obtained from this study were saved in the standard program of Statistical Package for Social Sciences for Windows 20. Numerical variables were summarized as mean ± SD (standard deviation), and categorical variables were summarized as numbers and percentages. Frequency analysis was performed.

Pulse ≤100 pulse/min

532 (77.1)

Pulse: 100–120 pulse/min

131 (19)

Pulse ≥120 pulse/min

27 (3.9)

Saturation O2 ≤89%

16 (2.3)

Saturation O2: 90-94%

81 (11.7)

Saturation O2 ≥95%

593 (85.9)

To determine the weights of the attributes, the Evolutionary Weighting algorithm was used in Model-1 and Model-2. Here, the presence or absence of pathology on X-ray radiography as model 1 and the presence and absence of pathology on thorax CT as model 2 are expressed. Evolutionary algorithms (EAs: Evolutionary Algorithms) are among the most commonly used algorithms for feature selection (FS). The basic mechanism of such algorithms is to optimize the defined objective function for FS and to obtain the best subset of features.[9] This algorithm includes the application of the evolutionary algorithm for feature weighting. The weights obtained provide quantitative information about the relative importance of the properties.[10] The optimization weight (evolutionary) operators calculate the weights of the attributes in the given data set using the genetic algorithm. The higher the weight of an attribute, the more relevant it is. Sensitivity or recall and specificity metrics were used to compare the performance of models created for feature selection. Sensitivity is the ratio of true positives correctly classified by the model. Specificity is the proportion of true negatives correctly classified by the 922

Reasons for requesting an X-ray

Because he’s over 60

169 (524.5)

Due to the sudden deceleration mechanism

209 (30.3)

Because the chest is pain

332 (48.1)

Because dyspnea

131 (19)

Because hypoxia (sat ≤95)

75 (10.9)

Due to hemoptysis

23 (3.3)

Due to thorax sensitivity by palpation

Lesion in the thoracic wall (such as seat

258 (37.4)

belt. abrasion)

Disturbing injury which cause to forget

62 (9)

the injury to the thorax

89 (12.9)

Due to abnormal lung auscultation

74 (10.7)

Due to impaired consciousness

49 (7.1)

Due to intoxication

11 (11.6)

SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Acar et al. Evaluation of the NEXUS X-ray rules in blunt thorax trauma

206 (29.9%) were injured due to falls and 449 (65.1%) patients applied to our emergency department by ambulance. It was found that 52 (7.5%) of the patients had systolic blood pressure below 90 mmHg at the time of admission to the emergency department, and 16 (2.3%) had oxygen saturation below 89%. Radiological examination indications for trauma were reported as chest pain in 332 patients (48.1%), thoracic sensitivity by palpation in 258 patients (37.4%), and radiological examination in 209 patients (30.3%) due to serious injury mechanism. The demographic values of the cases are given in Table 2. Radiological imaging of the trauma revealed 181 (26.2%) patients with chest trauma. Traumatic thoracic findings are presented in the table (Table 3). There were no additional injuries in 491 (71.2%) patients with multiple trauma, 52 (7.5%) patients with head, 23 (3.3%) patients with abdominal, 12 (1.7%) patients with pelvis, 11 (1%) 6) extremity and 62 (9%) patients had multiple trauma. 366 (53%) patients had no BT, whereas 324 (47%) patients had BT, although X-ray is normal, 63 (9.1%) patients due to suspected thoracic trauma. 136 (19.7%) patients had BT for detailed examination, 31 (4.5%) patients because of routine in thorax trauma, 95 (13.8%) patients for additional BT even though X-ray is abnormal. According to CT results, 88 (12.5%) patients had rib fractures and 24 (3.5%) patients had pneumothorax (Table 3). Table 3. Pathologies detected in X-Ray and thorax CT Pathologies Rib fractures

The findings showed that 111 (16.08%) patients with traumatic thoracic injuries were followed, 56 (8.11%) patients underwent tube thoracostomy and 14 (2%) patients were treated with mechanical ventilation. When hospitalizations were evaluated, 478 (70.6%) patients were discharged from the emergency department, 159 (23%) patients were admitted to the service, 40 (5.8%) patients were admitted to the intensive care unit and 4 (0.6%) patients were ex. When Model-1 results were evaluated, it was found that 11.2, 11.6 and 11.7 attributes were very significant for predicting the presence of pathology in X-ray. Sensitivity parameter of Model-1 was calculated as 0.983. In other words, Model-1 accurately estimates 98.3% of patients with pathology on X-ray. The estimated rate of patients without pathology is 37.9%. In addition, in Table 4, there is the complexity matrix of Model-1. According to this matrix, when the weight ratios given in Model-1 are used, 178 patients with pathology were classified as pathology, while three patients were incorrectly classified as no pathology. Similarly, 193 patients without pathology were classified as having no pathology, while 316 patients were incorrectly classified as having pathology (Table 5, 6). Table 5. Model-1 parameters Property Value

X-Ray Graphy

Thorax CT

n (%)

97 (14)

88 (12.7)

P crossover

Population size

Maximumnumber of the generations

Pneumothorax

38 (5.5)

24 (3.5)

Crossover type

Hemothorax

2 (0.28)

47 (6.8)

Selections scheme

Plumonary contusionx

20 (2.9)

14 (2)

Flail chest

6 (0.9)

Hemopneumothorax

36 (5.2)

40 (5.8)

Cardiovascular injury

5 (0.7)

Diaphragmatic injury

2 (0.28)

X: Flail chest was diagnosed clinically and radiologically. CT: Computed tomography.

0.6 Shuffle Roulette wheel

Table 6. Model-1 complexity matrix

True-no True-yes

Prediction X-Ray result no disea-se

193

316

Prediction X-Ray result has dise-ase

178

Table 4. Attribute weights and performance metrics

AttributeWeigth

Sensivity Specificity

Model 11.1 11.2 11.3 11.4 11.5 11.6 11.7 Model-1 0 1 0 0 1 0 1 98.3% 37.9% Model-2 0 0.96 0.56 0.56 1 0 1 Model 1: Pathology on X-Ray, Model 2: Pathology on thorax CT 11.1: Above 60 years of age, 11.2 Sudden deceleration mechanism, 11.3 chest pain, 11.4 chest wall sensitivity, 11.5 intoxication, 11.6 abnormal alertness / The mental state represents 11.7 irritating painful injuries.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

923

Acar et al. Evaluation of the NEXUS X-ray rules in blunt thorax trauma

Predicted class: 1

0.9

0.8

0.7

Predicted class: 2

0.832 SVM

TP Rate (Sensitivity)

0.6 0.5 0.4 0.3

0.7 0.6 0.5 0.4 0.3

0.2

0.1

0.164 SVM

0 0

0.1

0.2

0.3 0.4 0.5 0.6 0.7 FP Rate (1-Specificity)

0.8

0.9

0.1

0.2

0.3 0.4 0.5 0.6 0.7 FP Rate (1-Specificity)

0.8

0.9

Figure 1. Graph of the ROC curve obtained for the X-ray (a) and CT result (b) on the X-Ray after the analysis with the Orange program.

The strength of the diagnostic value for X-Ray if there is any pathology (No (1) and Yes (2) distinguishing power) is expressed by the area under the ROC curve. The diagnostic value increases as the field value approaches 1. At 100% diagnostic power, the field value is equal to 1. The results of the analysis performed with the Orange program in this study, , the ROC curve graphs obtained for are shown in Figure 1a and b that indicates the presence of pathology and CT results in the X-Ray. Support vector machines (SVM) were used as the classification method in the program.

DISCUSSION Trauma is the transfer of kinetic energy to the patient (acceleration, deceleration, or blastic) by different mechanisms. Traumatic damage may vary depending on the duration of the trauma, the mechanism of occurrence, the object or the physical structure of the patient. Thoracic traumas have been reported to be more common in young males.[13,14] In our study, the most common cause of thoracic trauma was an in-vehicle traffic accident. Males were the majority and the mean age of the patients was 45 years. Complaints of chest pain, thoracic tenderness with palpation and sudden deceleration mechanism criteria were requested in the patients and traumatic thoracic pathology was observed in approximately 25% of all images. The most common thoracic trauma was rib fracture. Thorax CT was requested in 45% of the patients for further examination. When the patients were evaluated according to nexus thorax radiography rules, sudden slowdown mechanism, intoxication and painful injury were found to be statistically significant in detecting trauma. The overall sensitivity and specificity of Nexus thorax radiographs were 98% and 38%, which was consistent with the literature.[6,8] According to the literature data, the most decisive criterion for blunt thoracic trauma has been reported to be the 924

mechanism of sudden deceleration.[6,8,15] In our study, it was concluded that one of the most important criteria concerning the indication of request for radiological examination and the detection of traumatic pathology is the sudden deceleration mechanism in accordance with the literature data. In addition, the symptom of chest pain in trauma was found to be as important and determinative as the criteria of sudden slowdown mechanism. Any condition that disrupts the consciousness of the person or the presence of additional injuries that may neglect the injury in the thorax is also the parameters that should be a serious stimulus for physicians. In our study, we found that 73% of patients underwent X-ray, 47% underwent thorax CT, and 25% of our patients had thoracic pathology, and the most common pathologies were rib fracture, pneumothorax and hemothorax. Safari et al.[16] stated that they detected the rate of radiography around 43% and most commonly seen jeans fracture and hemothorax. In another study, 43% of the patients underwent X-ray, 42% of them underwent CT, and 15% of the patients reported that they detected thoracic pathology and most commonly found rib fracture and pneumothorax.[6] In another study, it was stated that the rate of X-ray use was 50% and the rate of using CT was about 50%, and the rate of thoracic pathology was 15%.[15] As can be seen from the literature, CT scan results and detected pathologies are compatible with each other, but it will be seen that we take a little more X-ray at the rate of radiography. It may be difficult to determine why more is taken, but the aim of our study is to reduce the rate of radiography, which means that such studies are needed because we already believe that many graphics are required. In this context, we think that this result can be interpreted by us in accordance with the literature. Because it is considered a forensic case concerning trauma, physicians may be reluctant to evaluate a trauma patient and may require unnecessary radiographs and CTs to secure Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Acar et al. Evaluation of the NEXUS X-ray rules in blunt thorax trauma

them. At this point, the algorithms or scoring systems that will relieve the physician from this feeling of insecurity seem to be applicable concerning forensic/medical relief. This also applies to the patient. Patients get rid of irradiation due to unnecessary radiographs, and as a result of these systems, which have a sensitivity of almost 100%, they can be examined more safely with less radiation. There are many examples of this situation. For example, Canada Brain CT rules used in patients with head trauma have reduced the rate of brain CT scans by 30%, but the probability of patient skipping has decreased to almost 0%.[13] Of course, there is also a protocol now known as head-to-pelvis CT protocols. In this protocol, physicians undergo full-body CT to reduce time loss and minimize skippable injuries in patients with multiple trauma, hemodynamically unstable patients and even recommend this application by predicting less radiation from CTs to be taken separately.[17–19] Although it is very popular in this regard, ATLS instead focuses on system evaluations where physical examination and clinical evaluations are at the forefront.[20] This application of ATLS requires more clinical findings and physical examinations, the physician experience and the subjective evaluations of the physician more. With the scoring rules to be added to these practices, these subjective evaluations can be further secured with objective parameters and will comfort the patient and the physician. The algorithm or parameters that should be considered while developing such a rule are easy to apply and can be used for tracking purposes. From this perspective, it is evident that the rules of nexus thorax radiography are easy to apply parameters. It has been tried and found to be easy to apply in many studies, including our study.[15,21,22] One of the important parameters here is the omission of a potentially fatal injury is extremely critical and eliminates the implementation of the algorithm. In the previous studies in this context, the fatal injury - the aortic injury as the fatal injury - was not omitted and the reliability of the rules seems to be confirmed.[6] The absence of a fatal pathology missed in our study supports the previous studies and confirms the reliability of the rules. In this context, we think that the necessity of entering these parameters into the algorithms will be on the agenda soon. In conclusion, when the physicians note that the risk of nexus thorax radiography/CT is low risk in detail in the patient’s file, we think that the rules of nexus thorax radiography/CT will protect physicians both legally and conscientiously in patients with blunt thoracic trauma. In this context, we believe that these rules can be applied. However, medicine is an art. Physicians, who are practitioners of this art, should not forget to examine and follow the patient and try to integrate these rules, which we mentioned in the quality and effective examination. As long as this is realized, we think that the diagnosis will be minimal in patients. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.A.; Design: E.A., A.D.; Supervision: B.Y., R.M.K., A.Z Resource: A.D., G.Y.; Data: A.D., G.K., Ö.D.A.; Analysis: O.Ö; Literature search: E.A., Ö.D.A.; Writing: E.A.; Critical revision: B.Y., R.M.K., A.Z. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Ekeke ON, Okonta KE. Trauma: a major cause of death among surgical inpatients of a Nigerian tertiary hospital. Pan Afr Med J 2017;28:6. 2. Osime OC, Ighedosa SU, Oludiran OO, Iribhogbe PE, Ehikhamenor E, Elusoji SO. Patterns of trauma deaths in an accident and emergency unit. Prehosp Disaster Med 2007;22:75–8. 3. Shekhar C, Gupta LN, Premsagar IC, Sinha M, Kishore J. An epidemiological study of traumatic brain injury cases in a trauma centre of New Delhi (India). J Emerg Trauma Shock 2015;8:131–9. 4. Curran JA, Brehaut J, Patey AM, Osmond M, Stiell I, Grimshaw JM. Understanding the Canadian adult CT head rule trial: use of the theoretical domains framework for process evaluation. Implement Sci 2013;8:25. 5. Mata-Mbemba D, Mugikura S, Nakagawa A, Murata T, Kato Y, Tatewaki Y, et al. Canadian CT head rule and New Orleans Criteria in mild traumatic brain injury: comparison at a tertiary referral hospital in Japan. Springerplus 2016;5:176. 6. Rodriguez RM, Anglin D, Langdorf MI, Baumann BM, Hendey GW, Bradley RN, et al. NEXUS chest: validation of a decision instrument for selective chest imaging in blunt trauma. JAMA Surg 2013;148:940–6. 7. Nishijima DK, Simel DL, Wisner DH, Holmes JF. Does this adult patient have a blunt intra-abdominal injury?. JAMA 2012;307:1517–27. 8. Rodriguez RM, Hendey GW, Mower WR. Selective chest imaging for blunt trauma patients: The national emergency X-ray utilization studies (NEXUS-chest algorithm). Am J Emerg Med 2017;35:164–70. 9. Paul S, Das S. Simultaneous feature selection and weighting – An evolutionary multi-objective optimization approach. Pattern Recognition Letters 2015;65:51–9. 10. Komosiński M, Krawiec K. Evolutionary weighting of image features for diagnosing of CNS tumors. Artif Intell Med 2000;19:25–38. 11. Altman DG, Bland JM. Diagnostic tests. 1: Sensitivity and specificity. BMJ 1994;308:1552. 12. Parikh R, Mathai A, Parikh S, Chandra Sekhar G, Thomas R. Understanding and using sensitivity, specificity and predictive values. Indian J Ophthalmol 2008;56:45–50. 13. Wright DW, Merck LH. Head Trauma. In: Tintinalli JE, Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Cline DM. Tintinalli’s Emergency Medicine A Comprehensive Study Guide. 8th edition. McGraw-Hill Education 2016.p.1695–707. 14. Yalçınkaya İ, Sayır F, Kurnaz M, Çobanoğlu U. Chest trauma: analysis of 126 cases. Ulus Travma Acil Cerrahi Derg 2000;6:288–91. 15. Rodriguez RM, Langdorf MI, Nishijima D, Baumann BM, Hendey GW, Medak AJ, et al. Derivation and validation of two decision instruments for selective chest CT in blunt trauma: a multicenter prospective observational study (NEXUS Chest CT). PLoS Med 2015;12:e1001883.

925

Acar et al. Evaluation of the NEXUS X-ray rules in blunt thorax trauma 16. Safari S, Radfar F, Baratloo A. Thoracic injury rule out criteria and NEXUS chest in predicting the risk of traumatic intra-thoracic injuries: A diagnostic accuracy study. Injury 2018;49:959–62. 17. Long B, April MD, Summers S, Koyfman A. Whole body CT versus selective radiological imaging strategy in trauma: an evidence-based clinical review. Am J Emerg Med 2017;35:1356–62. 18. Nummela MT, Bensch FV, Pyhältö TT, Koskinen SK. Incidence and Imaging Findings of Costal Cartilage Fractures in Patients with Blunt Chest Trauma: A Retrospective Review of 1461 Consecutive Whole-Body CT Examinations for Trauma. Radiology 2018;286:696–704.

19. Furlow B. Whole-Body Computed Tomography Trauma Imaging. Radiol Technol 2017;89:159CT–80CT. 20. Parker RS, Parker PJ. One hundred years on: Ypres and ATLS. Emerg Med J 2017;34:766–7. 21. Stiell IG, Wells GA. Methodologic standards for the development of clinical decision rules in emergency medicine. Ann Emerg Med 1999;33:437–47. 22. Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta DC, Steiner J. Chart reviews in emergency medicine research: Where are the methods?. Ann Emerg Med 1996;27:305–8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Künt toraks travmasında Nexus X-ray kurallarının değerlendirilmesi Dr. Ethem Acar,1 Dr. Ahmet Demir,1 Dr. Birdal Yıldırım,1 Dr. Gökhan Kaya,1 Dr. Ömer Doğan Alataş,1 Dr. Rabia Mihriban Kılınç,2 Dr. Arife Zeybek,3 Dr. Osman Özkaraca4 Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Muğla Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Muğla Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, Muğla 4 Muğla Sıtkı Koçman Üniversitesi Teknoloji Fakültesi, Bilgisayar Donanımı Anabilim Dalı, Muğla 1 2 3

AMAÇ: Künt toraks travmasının değerlendirilmesi için hala kabul edilmiş bir radyografik kural yoktur. Acil hekimleri tecrübelerine ve muayene bulgularına göre radyografi istemektedirler. Bu konuda çeşitli çalışmalar yapılmış ve bu çalışmaların bir kısmında radyografi kurallarının ilk adımlarını destekleyebilecek sonuçlarda tespit edilmiştir. Bunlardan biri Nexus toraks radyografi kuralıdır. Çalışmamızda, Nexus toraks radyografi kurallarının doğruluğunu belirlemeyi amaçlıyoruz. GEREÇ VE YÖNTEM: Çalışmamız üniversite hastanemiz acil servisinde yapılan ileriye yönelik bir kohort çalışmasıdır. Çalışmada 690 hasta değerlendirildi. BULGULAR: Çalışmamız sonucunda göğüs ağrısı, palpasyonla toraksta hassasiyeti, ani yavaşlama mekanizması nedeniyle daha fazla toraks grafisi çekildiğini ve tüm görüntülemenin yaklaşık %25’inde patoloji tespit edildiği gözlenmiştir. En sık rastlanan patolojiler kaburga kırığı idi. Hastaların yaklaşık %45’ine toraks bilgisayarlı tomografi (BT) çekildi ve toraks BT en sık olarak detaylı inceleme için istendi. Hastaları Nexus toraks radyografi kurallarına göre değerlendirdiğimizde ani yavaşlama, zehirlenme ve rahatsız edici ağrılı yaralanma mekanizmasının diğer parametrelerden daha önemli olduğu görülmektedir. Nexus toraks radyografilerinin genel duyarlılığı ve özgüllüğü sırasıyla %98 ve %38 olarak bulundu. TARTIŞMA: Künt toraks travmasının değerlendirilmesinde, Nexus toraks radyografisi kuralları patolojik tanı açısından faydalı olarak değerlendirilmektedir. Anahtar sözcükler: Acil servis; künt toraks travması; Nexus kuralları. Ulus Travma Acil Cerrahi Derg 2020;26(6):920-926

926

doi: 10.14744/tjtes.2020.55594

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

A different approach to leakage of esophageal atresia in children Erol Basuguy, M.D., Mehmet Hanifi Okur, M.D., Hikmet Zeytun, M.D., Bahattin Aydoğdu, M.D.

Serkan Arslan, M.D.,

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

ABSTRACT BACKGROUND: In this study, we aimed to present the results of patients treated for esophageal leakage with a different conservative approach. METHODS: Ninety-eight patients with esophageal atresia and tracheoesophageal fistula (EA) who underwent surgery in our clinic between February 2013 and January 2018 were retrospectively reviewed in this study. Patients’ anastomosis leakage, gestational week, gender, body weight, referral date, recovery time and stenosis were recorded. After leakage detection, the nasogastric catheter was fluoroscopically converted into a nasojejunal catheter using a guidewire and feeding continued. RESULTS: Anastomotic leakage developed in 18 (18.3%) patients. The average gestational age at birth was 35.4 weeks; the patients included ten girls and eight boys of average weight 2.41 kg; the average referral period was 2.1 days after birth and the average time of surgery was 2.4 days after birth. The average recovery time was 21.1 days (range: 8–60 days). Eight patients developed stenosis that recovered with dilatation. CONCLUSION: Our findings suggest that our conservative treatment approach, which uses a nasojejunal catheter, is an effective method that would reduce complications, enable earlier feeding, and reduce the cost compared to other treatment approaches. Keywords: Children; esophagus; leakage; nasojejunal catheter.

INTRODUCTION Newborn esophageal atresia (EA) and trachea-esophageal fistulae (TEF) are relatively common congenital abnormalities with incidence rates of one in 2,500 and one in 4,500 live births.[1,2] Improvements in neonatal intensive care, anesthesia, and surgical techniques have considerably improved the survival rates of the patients with EA.[3] However, as the number of operations increases, the number of postoperative complications inevitably increases; therefore, the complications remain a concern.[4,5] One of the most common and severe complications following EA/TEF surgery is esophageal leakage; the incidence is approximately 15–17%.[6] Despite recent developments in pediatric surgery, some patients require re-operation, which remains a major surgical concern because the associated morbidity and mortality rates are rel-

atively high. In this study, we aimed to present the results of patients treated for esophageal leakage with a different conservative approach.

MATERIALS AND METHODS Ninety-eight patients with esophageal atresia and tracheoesophageal fistulae who underwent surgery at our clinic between February 2013 and January 2018 were retrospectively reviewed in this study. Patients with isolated EA were excluded from this study. All cases were graded using the Gross classification and surveyed using the SPITZ system. After preoperative stabilization, all patients were reviewed concerning genitourinary, cardiovascular, anorectal, and spinal abnormalities. Gestational week, gender, body weight, and referral date were recorded. Gap length was measured with a ruler

Cite this article as: Basuguy E, Okur MH, Arslan S, Zeytun H, Aydoğdu B. A different approach to leakage of esophageal atresia in children. Ulus Travma Acil Cerrahi Derg 2020;26:927-931. Address for correspondence: Erol Basuguy, M.D. Dicle Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Diyarbakır, Turkey Tel: +90 412 - 248 80 01 / 4718 E-mail: erbas.80@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):927-931 DOI: 10.14744/tjtes.2020.17745 Submitted: 31.12.2019 Accepted: 04.03.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

927

Basuguy et al. A different approach to leakage of esophageal atresia in children

during an operation before dissecting the fistula (short gaps: 72 patients, long gaps: 26 patients). We defined as a long gap length of ≥3 cm (the distance between the two ends of the esophagus).[7] Two groups were compared concerning leakage, stricture rates and leakage recovery time. Anastomotic leakage developed in 18 (18.3%) patients. The need for mechanical ventilation of these patients and the recovery times were recorded. All patients underwent thoracotomy using the right intercostal space (ICS) 4–5 while lying on the left. Continuously feeding was started 1–2 mL per hour of breast milk or formula using a nasogastric catheter on postoperative day 2, and the quantity of milk was gradually increased daily. Esophagography was performed on all patients who exhibited no thoracic tube discharge on postoperative day five and patients without leakage were started oral feeding. Patients were discharged with a recommendation for polyclinic follow-up two weeks later.

loon dilatation under general anesthesia. Our treatment algorithm for the management of anastomotic leakage is shown in Figure 2.

Patients who exhibited formula or saliva discharge using the thoracic tube underwent esophagography in a dedicated room at our clinic. After leakage detection (Fig. 1a), the nasogastric catheter was fluoroscopically converted into a nasojejunal catheter using a guidewire and feeding continued (Fig. 1b). The flow rate and nature of thoracic tube discharge were recorded daily. Any lung problems were noted. Secondary tubes were placed in five patients who developed pneumothorax that could not be controlled using a single tube. All radiological examinations were carried out in our clinic and/or at the bedside. Patients were monitored by performing complete blood counts, biochemical analyses, blood gas evaluations, culture antibiograms, and we obtained posterior-anterior lung X-rays. The antibiograms were used to guide the antibiotherapy of patients who developed leakage and to plan new therapies.

RESULTS

Patients who developed leakage were discharged with a recommendation for polyclinic follow-up two weeks after full oral feeding commenced if lung problems were absent. Follow-up esophageal scans were carried out for patients with complaints and patients developing stenosis underwent bal-

(a)

(b)

This study was approved by the Committee on Ethics in Non-interventional Clinical Studies of Dicle University, Faculty of Medicine (June 6, 2018; decision no. 56).

Statistical Analysis All statistical analyses were performed using SPSS for Windows software (ver. 15.0; SPSS Inc., Chicago, IL, USA). The chi-squared test was used to compare categorical data. The Kolmogorov–Smirnov test was employed to explore if numerical data were normally distributed; such data were compared using the t-test, whereas data with non-normal distributions were compared using the Mann–Whitney U test. A p-value <0.05 was considered to reflect statistical significance.

On gross EA classification, 17 patients were of type C and 1 of type D (with both a distal and proximal fistula). On SPITZ classification, 83.3% (n=15) of 18 patients who developed leakage were of Group 1, 11% (n=2) of Group 2, and 5.5% (n=1) of Group 3.

Management of esophageal atresia

Surgery

Postoperative second day nasogastric nutrition Tube drainage (–)

Tube drainage (+)

Postoperative

Esophagography and

fifth day

leakage detection

esophagography NG convert to NJ Leakage (–) NJ nutrition NG remove and oral start

Tube drainage (–)

Esophagography

Leakage

NJ remove and oral start

Figure 1. (a) Anastomotic leakage. (a) The Nasojejunal catheter.

928

Figure 2. Our treatment algorithm.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Basuguy et al. A different approach to leakage of esophageal atresia in children

complications after esophageal atresia (EA) repair. Despite improvements in the surgical correction of EA, postoperative leakage continues to be a significant problem. Leakage is af Short gap Long gap fected by many factors, including esophageal injury, excessive mobilization of the distal end of the esophagus, associated n (%) n (%) ischemia,[8] anastomotic tension,[9] poor suturing technique, the use of inappropriate sutures,[10,11] and a long gap length Patients 10 (14) 8 (31) and sepsis.[8–11] Of these, the gap length is of particular conGender cern, being an independent risk factor for leakage, a longer Male 4 4 gap length has been suggested to correlate with increased Female 6 4 leakage. Reported gap lengths vary; however, a gap length of Gestasyonel age 34.94 36.13 ≥3 cm (the distance between the two ends of the esophagus) is accepted as being long.[7] Weight 2.29 2.56 Table 1. Demographic data of the patients who developed leakage

Additional anomaly

Cardiac anomaly

5 (27.7)

2 (11)

Urogenital system

Gastrointestinal system

Mechanical ventilation

16.05

27.66

Infection

2 (11)

3 (16.6)

Stricture

3 (16.6)

5 (27.7)

Leakage recovery time (day)

The average gestational age at birth was 35.4 weeks; the patients included 10 girls and eight boys of average weight 2.41 kg; the average referral period was 2.1 days after birth, and the average time of surgery was 2.4 days after birth. Of the patients who developed leakage, eight (31%) patients had long gaps, and 10 (14%) patients had short gaps. The average recovery time was 21.1 days (range: 8–60 days). The most common additional problem was cardiac abnormalities in seven (38.8%) patients, of whom two patients exhibited genitourinary, two patients gastrointestinal, two patients limb, and one patient central nervous system abnormalities. One patient had VACTERL (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities). In total, five patients who developed leakage were intubated due to infection and lung problems. Signs of infection appeared in five patients during treatment; the treatment plans were thus changed. Eight patients developed stenosis, including five with long and three with short gaps; all underwent balloon dilatation. Multiple dilatations were performed to three patients and single balloon dilatations to five patients. Leakage developed in one patient after balloon dilatation and was corrected by conservative treatment. No problem was observed during the follow-up of patients who underwent dilatation. TEF relapse developed in one patient; surgical repair was performed. Demographic data, the details of the abnormalities, and the follow-up status of all patients are listed in Table 1.

DISCUSSION Anastomotic leakage is one of the most common severe Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

A previous study suggested that the leakage rate increased with gap length; the rate was 30% (15/50) in the cited work. [12] In contrast, Thakkar et al.[13] suggested that the gap length was not associated with the anastomotic leakage or stricture rate. However, we found that leakage, stricture rate, and leakage recovery time were significantly higher in patients with long gaps (p<0.05). Although different treatment approaches have been proposed, the optimal monitoring and treatment of leakage remain controversial. Some studies have recommended conservative treatment; other studies suggested that surgery is essential. However, the optimal surgical technique is still unclear. Some authors recommend early thoracotomy and re-anastomosis to optimize outcomes, whereas other authors favored gastric pull-up or colonic or jejunal transposition.[14–16] Koivusalo et al.[17] re-operated on 17 out of the 20 patients who developed leakages; anastomotic strictures developed in four patients, and one patient died. Chittmittrapap et al. [10] reported that esophageal leakage developed in 34 (17%) patients and six out of seven undergoing re-operation lost the native esophagus due to major disruptions. Early thoracotomy was recommended for such patients. Bawa et al.[18] monitored patients with esophageal leakage for an average of 12 days and then performed gastrostomy and jejunostomy (because of nutritional concerns) to treat patients in whom leakage persisted. Three of the patients developed jejunostomy tube-related complications and six patients died. Reoperation is considered dangerous due to continuous exposure of the tissue to gastric fluid and secretions in the case of postoperative leakage and may indicate that thoracotomy and re-anastomosis may be inappropriate. Other concerns include possible loss of the native esophagus, poor motility, reflux, and leakage.[6,15,19] Conservative treatments include chest tube placement, total parenteral nutrition (TPN), and wide-spectrum antibiotics. [20] Huang et al.[21] reported that 9% (n=3) of patients who underwent operations developed leakage; all recovered with conservative treatment. 929

Basuguy et al. A different approach to leakage of esophageal atresia in children

Vaghela et al.[22] reported that the use of glycopyrrolate, a secretion-reducing agent, was associated with more rapid leakage resolution, reduced need for mechanical ventilation, earlier enteral nutrition, and better preservation of the natural esophagus compared to the other group. They also suggested that enteral nutrition using slow infusion reduced gastroesophageal reflux (GER). However, secondary operations were required for two out of 21 patients in this group and the side-effects of this drug included constipation, urinary retention, dry mouth, and moniliasis. TPN may cause cholestasis, and a central venous catheter is required if TPN is long-term. Both catheter-associated complications and cardiovascular events may develop, increasing morbidity and mortality.[23–26] A previous study considered that enteral nutrition was more physiological, easier, and cheaper than TPN, without any need for a central venous catheter. This type of nutrition requires fewer laboratory tests and is associated with fewer complications.[27] Our treatment protocol was conservative in all patients, and this approach was noted in our previous clinical study.[28] We delivered enteral nutrition using a nasojejunal catheter after leakage detection, chest tube placement, and commencement of antibiotics. A nasojejunal catheter can be easily placed in newborns with the aid of scope; there is no need for anesthesia, and earlier enteral feeding is possible.

cerning mortality and morbidity. We believe that our conservative treatment approach, which uses a nasojejunal catheter, is an effective method that would reduce these complications, enable earlier feeding, and reduce the cost.

Acknowledgments The authors declare that there is no conflict of interest regarding the publication of this article. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.B.; Design: S.A.; Supervision: M.H.O.; Resource: E.B., S.A.; Materials: E.B.; Data: E.B., H.Z.; Analysis: H.Z., B.A.; Literature search: E.B., M.H.O.; Writing: E.B.; Critical revision: E.B., M.H.O., B.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Pinheiro PF, Simões e Silva AC, Pereira RM. Current knowledge on esophageal atresia. World J Gastroenterol 2012;18:3662–72. 2. Sulkowski JP, Cooper JN, Lopez JJ, Jadcherla Y, Cuenot A, Mattei P, et al. Morbidity and mortality in patients with esophageal atresia. Surgery 2014;156:483–91.

Our approach is physiological and patient-friendly; all required calories are delivered. Enteral nutrition did not trigger GER, although the quantity of food was increased daily. Therefore, TPN was not used. We thus prevented possible complications, such as cholestasis, cardiovascular events, and infection, arising from the use of a central catheter. Furthermore, the cost was able to be reduced since no TPN or central venous catheter was used. We believe that this approach, without any additional drugs or secondary surgery, effectively reduces complications and enables earlier feeding. Furthermore, the native esophagus is preserved.

3. Koivusalo AI, Pakarinen MP, Rintala RJ. Modern outcomes of oesophageal atresia: single centre experience over the last twenty years. J Pediatr Surg 2013;48:297–303.

Earlier studies reported mortality rates of approximately 30%; half of all mortality was caused by sepsis associated with the leakage of long gaps.[12] We performed preoperative risk classification using the Spitz system. Two patients (11.8%) died: No patient died in Group 1, one patient died in Group 2, and one patient died in Group 3. No patient died because of leakage per se or complications that arise from leakage.

8. Louhimo I, Lindahl H. Esophageal atresia: primary results of 500 consecutively treated patients. J Pediatr Surg 1983;18:217–29.

Conclusion Surgery performed to esophageal leakage may trigger severe complications, such as a difficult anastomosis, leakage, poor motility, and reflux, due to tissue fragility, the preferred approach remains conservative treatment. TPN, central catheter and the use of glycopyrrolate are possible risk factors in patients in whom conservative treatment is performed con930

4. Allin B, Knight M, Johnson P, Burge D; BAPS-CASS. Outcomes at oneyear post anastomosis from a national cohort of infants with oesophageal atresia. PLoS One 2014;9:e106149. 5. Pini Prato A, Carlucci M, Bagolan P, Gamba PG, Bernardi M, Leva E, et al. A cross-sectional nationwide survey on esophageal atresia and tracheoesophageal fistula. J Pediatr Surg 2015;50:1441–56. 6. Spitz L. Oesophageal atresia. Orphanet J Rare Dis 2007;2:24. 7. Castilloux J, Noble AJ, Faure C. Risk factors for short- and long-term morbidity in children with esophageal atresia. J Pediatr 2010;156:755– 60.

9. McKinnon LJ, Kosloske AM. Prediction and prevention of anastomotic complications of esophageal atresia and tracheoesophageal fistula. J Pediatr Surg 1990;25:778–81. 10. Chittmittrapap S, Spitz L, Kiely EM, Brereton RJ. Anastomotic leakage following surgery for esophageal atresia. J Pediatr Surg 1992;27:29–32. 11. Holder TM, Cloud DT, Lewis JE Jr, Pilling GP. Esophageal atresia and tracheoesophageal fistula: a survey of its members by the surgical section of the American Academy of Pediatrics. Pediatrics 1964;34:542–9. 12. Upadhyaya VD, Gangopadhyaya AN, Gupta DK, Sharma SP, Kumar V, Pandey A, et al. Prognosis of congenital tracheoesophageal fistula with esophageal atresia on the basis of gap length. Pediatr Surg Int 2007;23:767–71. 13. Thakkar HS, Cooney J, Kumar N, Kiely E. Measured gap length and outcomes in oesophageal atresia. J Pediatr Surg 2014;49:1343–6.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Basuguy et al. A different approach to leakage of esophageal atresia in children 14. D’Urzo C, Buonuomo V, Rando G, Pintus C. Major anastomotic dehiscence after repair of esophageal atresia: conservative management or reoperation?. Dis Esophagus 2005;18:120–3. 15. Spitz L. Esophageal atresia. Lessons I have learned in a 40-year experience. J Pediatr Surg 2006;41:1635–40. 16. Sharma S, Gupta DK. Surgical techniques for esophageal replacement in children. Pediatr Surg Int 2017;33:527–50. 17. Koivusalo AI, Pakarinen MP, Lindahl HG, Rintala RJ. Revisional surgery for recurrent tracheoesophageal fistula and anastomotic complications after repair of esophageal atresia in 258 infants. J Pediatr Surg 2015;50:250–4. 18. Bawa M, Menon P, Mahajan JK, Peters NJ, Garge S, Rao KL. Role of feeding jejunostomy in major anastomotic disruptions in esophageal atresia: A pilot study. J Indian Assoc Pediatr Surg 2016;21:24–7. 19. Gupta DK, Sharma S, Arora MK, Agarwal G, Gupta M, Grover VP. Esophageal replacement in the neonatal period in infants with esophageal atresia and tracheoesophageal fistula. J Pediatr Surg 2007;42:1471–7. 20. Zhao R, Li K, Shen C, Zheng S. The outcome of conservative treatment for anastomotic leakage after surgical repair of esophageal atresia. J Pediatr Surg 2011;46:2274–8. 21. Huang J, Tao J, Chen K, Dai K, Tao Q, Chan IH, et al. Thoracoscopic

repair of oesophageal atresia: experience of 33 patients from two tertiary referral centres. J Pediatr Surg 2012;47:2224–7. 22. Vaghela MM, Mahajan JK, Sundram J, Bhardwaj N, Rao KL. Role of glycopyrrolate in healing of anastomotic dehiscence after primary repair of esophageal atresia in a low resource setting-A randomized controlled study. J Pediatr Surg 2017;52:420–3. 23. Chesshyre E, Goff Z, Bowen A, Carapetis J. The prevention, diagnosis and management of central venous line infections in children. J Infect 2015;71:S59–75. 24. Patel SB, Ade-Ajayi N, Kiely EM. Oesophageal atresia: a simplified approach to early management. Pediatr Surg Int 2002;18:87–9. 25. Suri S, Eradi B, Chowdhary SK, Narasimhan KL, Rao KL. Early postoperative feeding and outcome in neonates. Nutrition 2002;18:380–2. 26. Warren M, Thompson KS, Popek EJ, Vogel H, Hicks J. Pericardial effusion and cardiac tamponade in neonates: sudden unexpected death associated with total parenteral nutrition via central venous catheterization. Ann Clin Lab Sci 2013;43:163–71. 27. Welch TD. Nutrition Options in Critical Care Unit Patients. Crit Care Nurs Clin North Am 2018;30:13–27. 28. Çimen H. Management of anastomotic leaks after primary esophageal atresia repair. Thesis. Diyarbakır, 2014.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Çocuklarda özofagus atrezisi kaçaklarına farklı bir yaklaşım Dr. Erol Basuguy, Dr. Mehmet Hanifi Okur, Dr. Serkan Arslan, Dr. Hikmet Zeytun, Dr. Bahattin Aydoğdu Dicle Üniversitesi Tıp Fakültesi, Çocuk Cerrahi Anabilim Dalı, Diyarbakır

AMAÇ: Farklı bir konservatif yaklaşımla özofagus kaçağı nedeniyle tedavi edilen hastaların sonuçlarını sunmayı amaçladık. GEREÇ VE YÖNTEM: Kliniğimizde Şubat 2013–Ocak 2018 tarihleri arasında trakeoözofageal fistüllü özofagus atrezisi (EA) nedeniyle ameliyat edilen olan 98 hasta geriye dönük olarak incelendi. Anastomoz kaçağı olan hastalarda gebelik haftası, cinsiyet, vücut ağırlığı, başvuru günü, iyileşme süresi ve stenoz kaydedildi. Kaçak tespitinden sonra, nazogastrik kateter floroskopik olarak bir kılavuz tel kullanılarak nazojejunal katetere dönüştürüldü ve beslenme devam etti. BULGULAR: Anastomoz kaçağı 18 (%18.3) hastada gelişti. Ortalama gebelik yaşı yaşı 35.4 haftaydı; hastaların onu kız ve sekizi erkekti. Ortalama ağırlık 2.41 kg idi. Başvuru günü doğumdan sonra ortalama 2.1 gün ve ortalama ameliyat zamanı doğumdan sonra 2.4 gün idi. Ortalama iyileşme süresi 21.1 gündü (8–60 gün). Sekiz hastada dilatasyon ile iyileşen darlık gelişti. TARTIŞMA: Nazojejunal kateter kullanılarak yapılan konservatif tedavi yaklaşımımızın diğer tedavi yaklaşımlarına kıyasla komplikasyonları azaltıp, erken beslenmeyi sağlayacak ve maliyeti düşürecek etkili bir yöntem olduğuna inanıyoruz. Anahtar sözcükler: Çocuklar; kaçak; nazojejunal kateter; özofagus. Ulus Travma Acil Cerrahi Derg 2020;26(6):927-931

doi: 10.14744/tjtes.2020.17745

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

931

ORIGIN A L A R T IC L E

Different approaches in diagnosis, follow-up and treatment of acute biliary pancreatitis: Results of attitude survey Erkan Somuncu, M.D.,1 İnanç Şamil Sarıcı, M.D.,1 Mehmet Celal Kızılkaya, M.D.,1 Yasin Kara, M.D.,1 Talha Sarıgöz, M.D.,2 Yusuf Sevim, M.D.,2 Tansu Altıntaş, M.D.,1 Musa Diri, M.D.,1 Betül Zeynep Yıldız, M.D.,1 Rıdvan Gökay, M.D.,1 Cenk Özkan, M.D.,1 Osman Sıbıç, M.D.,1 Adem Özcan, M.D.,1 Ceren Basaran, M.D.,1 Mustafa Uygar Kalaycı, M.D.1 1

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

Department of General Surgery, University of Health Sciences, Kayseri City Hospital, Kayseri-Turkey

ABSTRACT BACKGROUND: Acute biliary pancreatitis is one of the most frequently encountered diseases among general surgeons in emergency surgical diseases. Differences in diagnosis and treatment management of these patients, varying from physician to physician, are common in clinical practice. We aimed to present these differences and discuss the results in the light of current guidelines in the literature. METHODS: In this study, 21 questions were prepared regarding the physicians’ approach in the diagnosis, follow-up and treatment of acute biliary pancreatitis (Appendix).The questionnaires were completed by face to face interviews with 94 general surgery specialists at the 20th National Surgery Congress. RESULTS: In this study, 38 (40%) of the physicians who answered the questionnaire were working in the Training and Research Hospital, 27 (29%) in the State Hospital, 19 (20%) in the University Hospital and nine in private health care was working in the establishment. 85% of the physicians were general surgery specialists with 10 years of experience. 53% (50) of the surgeons reported that they had less than five cases of acute biliary pancreatitis each month, and 35% (34) stated that they wanted amylase value daily for follow-up. Ultrasonography and computed tomography were the most commonly used imaging modalities and 15% of the respondents indicated that each patient underwent magnetic resonance cholangiopancreatography. 45% of surgeons stated that antibiotics were started at the time of diagnosis of pancreatitis. The percentage of surgeons who did not undergo cholecystectomy early in patients with mild to moderate pancreatitis was 60%. The reason for not preferring surgery in the early period was the most frequent operation difficulty with 40% and not supporting the operation in the early period. CONCLUSION: According to the attitude survey results, there are differences between general surgery specialists in the diagnosis, follow-up and treatment of acute biliary pancreatitis. Keywords: Acute biliary pancreatitis; an attitude survey of pancreatitis; management of pancreatitis.

INTRODUCTION Acute pancreatitis is a common gastrointestinal disease with high morbidity and mortality rates worldwide.[1,2] Many guidelines have been published by different gastroenterology and surgical communities for the management of acute pancreatitis. In 2010, nearly 30 guidelines for the management of acute pancreatitis were analyzed in a study. The quality score of

the American College of Gastroenterology (ACG) guidelines (revised in 2013) is the highest among the American-based guidelines.[2] In addition, there are three other approved international guidelines–British Gastroenterology Association guidelines, the Japan Association of Abdominal Emergency Medicine guidelines, and the International Association of Pancreatology (AP) guidelines.[3–5] Some institutions also have their own guidelines.[6]

Cite this article as: Somuncu E, Sarıcı İŞ, Kızılkaya MC, Kara Y, Sarıgöz T, Sevim Y, et al. Different approaches in diagnosis, follow-up and treatment of acute biliary pancreatitis: Results of attitude survey. Ulus Travma Acil Cerrahi Derg 2020;26:932-936. Address for correspondence: Erkan Somuncu, M.D. SBÜ İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, İstanbul, Turkey Tel: +90 212 - 404 15 00 E-mail: dr.somuncu@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(6):932-936 DOI: 10.14744/tjtes.2020.72472 Submitted: 14.10.2019 Accepted: 17.04.2020 Online: 27.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

932

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Somuncu et al. Different approaches in diagnosis, follow-up and treatment of acute biliary pancreatitis

This study aimed to make an evidence-based presentation and prepare a national guideline for the management of severe acute pancreatitis by evaluating the feedback provided by general surgical specialists who attended the National Surgical Congress.

private hospitals and university hospitals. Based on this fact, post-hoc power analysis of the current survey study revealed a value of 36.8% when alpha was accepted at 0.05 using MedCalc v19.1 statistical software (MedCalc Software Ltd, Ostend, Belgium).

MATERIALS AND METHODS

RESULTS

This study included a survey of surgeon preferences in the management of acute pancreatitis. All the respondents, who were specialists in general surgery, interviewed during the National Surgery Congress, were asked to answer a questionnaire, which was designed after a thorough evaluation of the international guidelines (Appendix). Only 100 answered questionnaires were used for the survey. Critical topics were identified according to the American College of Gastroenterology (ACG) guidelines and the recommendations were accepted as correct. SPSS 22.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. The distribution of the answers was expressed as a percentage.

In this study, 94 participants were included. Eleven (12%) patients were female and 83 (88%) were male. All the participants were general surgery specialists. The participants were divided into five groups according to the institutions they worked at, and 84 (90%) specialists were employed at non-profit hospitals. As summarized in Table 1, 51 (54%) experts had more than 10 years of experience. Regardless of the type and severity of pancreatitis, 66 (70%) participants believed that hospitalization was required for the patients. All participants gave priority to amylase and CRP values during clinical follow-up; however, they also considered other parameters, such as leukocyte, lipase, AST, ALT, and bilirubin values. In addition to imaging methods, such as ultrasound and computed tomography (CT), the majority of the participants preferred magnetic resonance cholangiopancreatography (MRCP) alone without the upper abdominal sections. Seventy-four (78%) participants stated that MRCP must be performed only when the bilirubin levels are elevated. In addition, 54 (57%) institutions performed endoscopic retrograde cholangiopancreatography (ERCP). For the management of biliary pancreatitis, 78 (82%) participants stated that they definitely evaluated the Ranson and Atlanta criteria. The correct response rate in two critical topics, enteral nutrition and

Health services in Turkey consist of non-profit government hospitals, training and research hospitals, university hospitals, and private hospitals. Since there is no emergency or trauma subspecialization in the general surgery curriculum, general surgery specialists handle the management of acute biliary pancreatitis in Turkey. Therefore, this survey was conducted only with general surgery specialists. According to a recent study conducted by Yastı et al.,[7] in Turkey, 48.4% of specialists in general surgery worked at hospitals affiliated with the Ministry of Health and the remaining specialists worked in Table 1. Professional experience in general surgery (PEG)

PEG-1 PEG-2 PEG-3 PEG-4 PEG-5 PEG-6

Number of participants 15 28 22 14 7 8 Percentage

15.9% 29.6% 23.9% 14.6% 7.4% 8.6%

*PEG-1: <5 years; PEG-2: 6–10 years; PEG-3: 11–15 years; PEG-4: 16–20 years; PEG-5: 21–25 years; PEG-6: >25 years. All participants in this study are general surgical assistants and specialists at the National Surgery Congress.

Table 2. Correct answers rate among participants Total participant (n=94) PEG-1

Initial management of AP 40%

The role of ERCP in AP

The role of antibiotics in AP

Nutrition in AP

The role of surgery in AP

40% 46.6% 60% 60%

PEG-2

67.8%

32.1%

60.7% 57.1% 35.7%

PEG-3

86.3%

45.4%

54.5% 54.5% 45.4%

PEG-4

87.1%

42.8% 42.8% 50% 42.8%

PEG-5

90.7%

28.5%

57.1% 28.5% 42.8%

PEG-6

100%

37.5%

25% 37.5% 50%

AP: Acute pancreatitis; ERCP: Endoscopic retrograde cholangiopancreatography; PEG-1: Professional experience <5 years; PEG-2: Professional experience 6–10 years; PEG3: Professional experience 11–15 years; PEG-4: Professional experience 16–20 years; PEG-5: Professional experience 21–25 years; PEG-6: Professional experience >25 years.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

933

Somuncu et al. Different approaches in diagnosis, follow-up and treatment of acute biliary pancreatitis

100

Correct answer rate of all participants according to critical topics

90 80

Participants (%)

80 80 80 80 80 80 80 0

C Critical topics

A: Initial management AP C: Role of antibiotics in AP E: Role of surgery in AP

B: Role of ERPC in AP D: Nutrition in AP

Figure 1. The correct response rate given by the participants to the critical topics and responses determined according to the American Collage of Gastroenterology (ACG) published in 2013.

the role of antibiotics, in the guideline was 48 (51%) and 36 (39%), respectively. In patients with mild to moderate pancreatitis, 41 (44%) participants supported early cholecystectomy, and 19 (20%) participants did not agree with this approach. In addition, late cholecystectomy was preferred by 41 (43%) participants for patients with severe pancreatitis. Thirty-six (38%) participants suggested cholecystectomy in patients with biliary pancreatitis who had undergone sphincterotomy during ERCP. According to the experience of the participants, the rates of correct answers for critical topics are shown in Table 2, and the overall success percentage in the questions is shown in Figure 1.

DISCUSSION Acute pancreatitis is an inflammatory condition of the pancreas with a mild form that can be rapidly improved via fluid resuscitation, pain and nausea management, and early oral nutrition in the majority of patients. Often, the cause of pancreatitis is gallstones or excessive alcohol use and usually requires hospitalization. Acute pancreatitis may be more severe in 20â&#x20AC;&#x201C;30 percent of the patients and may be fatal in 15 percent of the patients.[8] Gastroenterologists and surgeons most often use the Atlanta classification revised in 2013 and international consensus definitions for acute pancreatitis. According to this classification, we usually encounter a mild form of the disease, which recovers in the first week without organ failure and local or systemic complications. However, patients with a moderate form of the disease exhibit temporary (less than 48 h) organ failure, local complications, or exacerbation of the co-morbid disease. Patients suffering from a severe form of the disease exhibit persistent organ failure (over 48 h). Worsening organ dysfunction in severe acute pancreatitis is associated with necrosis of the pancreas and associated 934

infection.[2] In a meta-analysis of 6970 patients, the mortality rate was 35.2% in patients with infected necrosis and organ failure, while the mortality rate was 1.4% if they had undergone infected necrosis without organ failure or sterile necrosis and organ failure.[9] Currently, early enteral nutrition in severe acute biliary pancreatitis, evaluation of prophylactic antibiotics, avoidance of surgery in patients with sterile necrosis, a more conservative approach to infected necrosis, various trends in endoscopic or surgical treatment, and management of the disease have changed our clinical practice.[10] As with any disease, evidence-based therapy is necessary to provide high-quality care with better outcomes in acute pancreatitis patients. Several studies have been conducted by surgeons and clinicians to demonstrate that acute pancreatitis does not meet management standards.[11,12] Mortality rates in acute pancreatitis are influenced by many factors, such as etiology, age, comorbid diseases, degree of pancreatic necrosis, and multiple organ failure.[13,14] In practice, early aggressive fluid replacement and early enteral nutrition are recommended for the management of acute pancreatitis. These guidelines also agreed that invasive procedures, such as endoscopic sphincterotomy and antibiotics in selected patients, are beneficial in acute cholangitis.[15] A previous study reported improvements concerning complications, duration of hospital stay, and morbidity and mortality rates of patients followed and treated according to the standard guidelines or protocols.[16] There are many obstacles, including the lack of knowledge of surgeons and the lack of clinical decision support tools, which may lead to non-compliance or poor compliance with standard guidelines. Despite all the barriers, training of major physicians and better definition of clinical decision support tools have resulted in tighter adherence to the guidelines and better clinical outcomes during the management of acute pancreatitis.[15,16] A similar survey study, which addressed the lack of knowledge of physicians, was conducted with internal medicine and surgical physicians at Abington Jefferson Health; however, the proportion of surgical physicians was relatively low.[17] We should note that similar results in our study indicated a lack of knowledge among the physicians. Another survey, published in 2012, was conducted with 240 (45%) participants from 49 countries. In this study, classifying the severity of acute pancreatitis based on the Atlanta approach was considered to be insufficient by the majority of the participants.[18] Hence, it is unclear how many international guides could be adequately used at the national level. A survey involving 54% of the Union of Surgeons of Great Britain and Ireland showed that only a small number of surgeons believed in the benefits of early laparoscopic cholecystectomy in patients with acute biliary pancreatitis.[19] Similarly, our results also suggested that early laparoscopic cholecysUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Somuncu et al. Different approaches in diagnosis, follow-up and treatment of acute biliary pancreatitis

tectomy is not preferred, but a forward referral is preferred by the surgeons. Surgeons, clinicians, or physicians performing initial evaluation need further training on the guidelines for the management of acute pancreatitis. This can only be achieved by organizing training courses and changing the established rules of the hospitals. To achieve better medical outcomes, it is necessary to establish a national-level admission order form, based on the standard guidelines for the early management of acute pancreatitis, as defined in the electronic medical records of hospitals and agreed by the surgeons. In addition, examinations, such as ERCP and MRI, can be expanded, and operating room and intensive care conditions can be improved by the Ministry of Health. For the management of acute pancreatitis, it is critical and necessary that the surgeons and clinicians who evaluate the patients in the emergency department have a good knowledge of the current guidelines.[2,3,6,20–22] The limitation of this study was that it was a survey conducted at a single national surgical congress with surgeons who have gained experience in the field of gastroenterology. It constituted only 48% of the surgeons attending the congress and was relatively low. It did not include other specialist clinicians and general practitioners who have evaluated the cases of acute pancreatitis.

Conclusions In general, the majority of our surgeons who answered the survey questions regarding the management of acute pancreatitis agreed on the answers to the questions. This survey showed that the surgeons did not have adequate information about the initial assessment, risk classification, fluid resuscitation, antibiotics, enteral nutrition, and the role of ERCP in acute pancreatitis management. That other clinicians and emergency department practitioners who were not yet specialized in this study were not included in the survey study prevented the comparisons between physicians. However, the findings of this survey could help provide guidelines for the management of acute pancreatitis. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.S., İ.Ş.S.; Design: E.S., İ.Ş.S.; Supervision: E.S., İ.Ş.S.; Resource: E.S., İ.Ş.S., M.C.K., Y.K., T.A., T.S., Y.S.; Materials: E.S., İ.Ş.S., M.D., B.Z.Y., R.G., C.Ö., O.S., A.Ö. C.B.; Data: E.S., İ.Ş.S., M.D., B.Z.Y., R.G., C.Ö., O.S., A.Ö., C.B.; Analysis: E.S., İ.Ş.S.; Literature search: E.S., Y.K.; Writing: E.S., Y.K.; Critical revision: E.S., İ.Ş.S., Y.K., M.U.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Talley NJ, Locke GR, Moayyedi P, West J, Ford AC. GI Epidemiology:

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Diseases and Clinical Methodology. 2nd Edition. New Jersey, USA: John Wiley & Sons; 2014. 2. Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108:1400–16. 3. Working Party of the British Society of Gastroenterology; Association of Surgeons of Great Britain and Ireland; Pancreatic Society of Great Britain and Ireland; Association of Upper GI Surgeons of Great Britain and Ireland. UK guidelines for the management of acute pancreatitis. Gut 2005;54:iii1–9. 4. DiMagno MJ. Clinical update on fluid therapy and nutritional support in acute pancreatitis. Pancreatology 2015;15:583–8. 5. Loveday BP, Srinivasa S, Vather R, Mittal A, Petrov MS, Phillips AR, et al. High Quantity and Variable Quality of Guidelines for Acute Pancreatitis: A Systematic Review. Am J Gastroenterol 2010;105:1466–76. 6. Greenberg JA, Hsu J, Bawazeer M, Marshall J, Friedrich JO, Nathens A, et al. Clinical practice guideline: management of acute pancreatitis. Can J Surg 2016;59:128–40. 7. Yastı AÇ, Uçar AD, Kendirci M. General surgery specialism in Turkey: work power currently, continuity at quality and quantity. Turk J Surg 2019;36:82–95. 8. van Santvoort HC, Bakker OJ, Bollen TL, Besselink MG, Ahmed Ali U, Schrijver AM, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology 2011;141:1254–63. 9. Werge M, Novovic S, Schmidt PN, Gluud LL. Infection increases mortality in necrotizing pancreatitis: A systematic review and meta-analysis. Pancreatology 2016;16:698–707. 10. Leppäniemi A, Tolonen M, Tarasconi A, Segovia-Lohse H, Gamberini E, Kirkpatrick AW, et al. 2019 WSES guidelines for the management of severe acute pancreatitis. World J Emerg Surg 2019;14:27. 11. Vlada AC, Schmit B, Perry A, Trevino JG, Behrns KE, Hughes SJ. Failure to follow evidence-based best practice guidelines in the treatment of severe acute pancreatitis. HPB (Oxford) 2013;15:822–7. 12. Sun E, Tharakan M, Kapoor S, Chakravarty R, Salhab A, Buscaglia JM, et al. Poor compliance with ACG guidelines for nutrition and antibiotics in the management of acute pancreatitis: a North American survey of gastrointestinal specialists and primary care physicians. JOP 2013;14:221–7. 13. Pitchumoni CS, Patel NM, Shah P. Factors influencing mortality in acute pancreatitis: can we alter them?. J Clin Gastroenterol 2005;39:798–814. 14. de Beaux AC, Palmer KR, Carter DC. Factors influencing morbidity and mortality in acute pancreatitis; an analysis of 279 cases. Gut 1995;37:121–6. 15. Rebours V, Lévy P, Bretagne JF, Bommelaer G, Hammel P, Ruszniewski P. Do guidelines influence medical practice? Changes in management of acute pancreatitis 7 years after the publication of the French guidelines. Eur J Gastroenterol Hepatol 2012;24:143–8. 16. Pupelis G, Austrums E, Snippe K. Importance of a clinical protocol in the treatment of severe acute pancreatitis. [Article in German] Zentralbl Chir 2002;127:975–81. 17. Mehmood A, Ullah W, Chan V, Ringold D. The Assessment of Knowledge and Early Management of Acute Pancreatitis Among Residents. Cureus 2019;11:e4389. 18. Petrov MS, Vege SS, Windsor JA. Global survey of controversies in classifying the severity of acute pancreatitis. Eur J Gastroenterol Hepatol 2012;24:715–21. 19. Senapati PS, Bhattarcharya D, Harinath G, Ammori BJ. A survey of the timing and approach to the surgical management of cholelithiasis in pa-

935

Somuncu et al. Different approaches in diagnosis, follow-up and treatment of acute biliary pancreatitis tients with acute biliary pancreatitis and acute cholecystitis in the UK. Ann R Coll Surg Engl 2003;85:306–12. 20. Yokoe M, Takada T, Mayumi T, Yoshida M, Isaji S, Wada K, et al. Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines 2015. J Hepatobiliary Pancreat Sci 2015;22:405–32. 21. Isaji S, Takada T, Mayumi T, Yoshida M, Wada K, Yokoe M, et al. Re-

vised Japanese guidelines for the management of acute pancreatitis 2015: revised concepts and updated points. J Hepatobiliary Pancreat Sci 2015;22:433–45. 22. Liao WC, Tu TC, Lee KC, Tseng JH, Chen MJ, Sun CK, et al. Taiwanese consensus recommendations for acute pancreatitis. J Formos Med Assoc 2020;119:1343–52.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut biliyer pankreatit tanısında, izleminde ve tedavisinde farklı yaklaşımlar: Tutum anketi sonuçları Dr. Erkan Somuncu,1 Dr. İnanç Şamil Sarıcı,1 Dr. Mehmet Celal Kızılkaya,1 Dr. Yasin Kara,1 Dr. Talha Sarıgöz,2 Dr. Yusuf Sevim,2 Dr. Tansu Altıntaş,1 Dr. Musa Diri,1 Dr. Betül Zeynep Yıldız,1 Dr. Rıdvan Gökay,1 Dr. Cenk Özkan,1 Dr. Osman Sıbıç,1 Dr. Adem Özcan,1 Dr. Ceren Basaran,1 Dr. Mustafa Uygar Kalaycı1 1 2

Sağlık Bilimleri Üniversitesi İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, İstanbul Kayseri Şehir Hastanesi, Genel Cerrahi Kliniği, Kayseri

AMAÇ: Akut biliyer pankreatit, acil cerrahi hastalıklarda genel cerrahlar arasında en sık karşılaşılan hastalıklardan biridir. Hekimden hekime değişen bu hastaların tanı ve tedavi yönetimindeki farklılıklar klinik uygulamada sık görülür. Bu farklılıkları sunmayı ve sonuçları literatürdeki güncel kılavuzlar ışığında tartışmayı amaçladık. GEREÇ VE YÖNTEM: Akut biliyer pankreatit tanısında, takibinde ve tedavisinde hekimlerin yaklaşımlarına ilişkin 21 soru hazırlandı (Ek-A). Anketler, 20. Ulusal Cerrahi Kongresi’nde 94 genel cerrahi uzmanıyla yüz yüze görüşülerek dolduruldu. BULGULAR: Anketi cevaplayan hekimlerin 38’i (%40) eğitim ve araştırma hastanesinde, 27’si (%29) devlet hastanesi’nde, 19’u (%20) üniversite hastanesinde ve 9’u özel sağlık kuruluşunda çalışmakta idi. Hekimlerin %85’i 10 yıllık deneyime sahip genel cerrahi uzmanlarıydı. Cerrahların %53’ü (50) her ay beşten az akut biliyer pankreatit vakası gördüğünü ve %35’i (34) takip için günlük olarak amilaz değeri istediklerini belirtti. Ultrasonografi ve bilgisayarlı tomografi en sık kullanılan görüntüleme yöntemleri idi ve yanıt verenlerin %15’i her hastaya manyetik rezonans kolanjiyopankreatografi yaptığını belirtti. Cerrahların %45’i pankreatit tanısı sırasında antibiyotik başladığını belirtti. Hafif-orta şiddette pankreatitli hastalarda erken dönemde kolesistektomi yapmayan cerrahların oranı %60 idi. Erken dönemde ameliyatı tercih etmeme nedeni %40 ile en sık ameliyat zorluğu ve ameliyatı erken dönemde desteklememe fikri idi. TARTIŞMA: Tutum anketi sonuçlarına göre akut biliyer pankreatit tanısı, takibi ve tedavisinde genel cerrahi uzmanları arasında farklılıklar bulunmaktadır. Anahtar sözcükler: Akut biliyer pankreatit; pankreatit için tutum anketi; pankreatitin yönetimi. Ulus Travma Acil Cerrahi Derg 2020;26(6):932-936

doi: 10.14744/tjtes.2020.72472

Appendix. Approach and attitude in acute biliary pancreatitis 1.

How many years have you been working as a surgical specialist? a) <5 years b) 5–10 years c) 10–15 years d) 15–20 years e) 20–25 years f) >25 years 2. How many days in a month can you perform surgery in your hospital? a) 1 day b) 2 days c) 3 days d) 4 days e) ≥5 days 3. Do you have an intensive care unit in the hospital? a) Yes b) No 4. How many biliary pancreatitis cases you encounter in a month in the hospital? a) <5 b) 5–10 c) ≥10 5. What are the most important biochemical parameters in the management of acute pancreatitis? a) Leukocyte count b) Amylase c) Lipase d) Liver function tests e) The level of bilirubin f ) CRP 6. How often do you want to see the amylase value? a) Everyday b) It is enough to look at the diagnosis 7. When do you start antibiotics on the patient in the management of pancreatitis? a) In any case, I start b) In case of high fever c) In the presence of complications d) In the presence of infection on radiological examination 8. When do you start oral nutrition to the patient? a) I do not stop b) According to the tolerability of oral nutrition c) According to laboratory values and imaging results d) I stop oral feeding independently of all factors 9. Which imaging methods do you often prefer? a) US b) CT c) MR d) MRCP 10. When would you prefer to hospitalize the patient? a) Never b) If the Ranson score is >3 c) Always

936

11. When do you perform MRCP? a) Always b) According to laboratory values c) Never 12. Can you perform abdominal CT according to Ranson criteria? a) Never b) If the Ranson score is >3 c) Always 13. When do you perform cholecystectomy in a case of mild-moderate biliary pancreatitis? a) Normal laboratory values during hospitalization b) Within 2 weeks c) Within 2–4 weeks d) Within 4–8 weeks e) After 8 weeks 14. Why do not you prefer cholecystectomy early? a) Busy work b) Time-consuming documentation c) No room in hospital d) Surgery is technically difficult in this period e) I do not recommend early cholecystectomy 15. Can you consider Atlanta criteria before cholecystectomy? a) Always b) Sometimes c) Never 16. When do you perform a cholecystectomy in a patient with severe biliary pancreatitis? a) When laboratory values are normalized b) Observing complications within 2 weeks c) Within 4–8 weeks d) After 8 weeks 17. Is ERCP performed in your hospital? a) Yes b) No 18. When to perform cholecystectomy in patients undergoing sphincterotomy via ERCP? a) When laboratory values are normalized b) Within 2 weeks c) Within 2–4 weeks d) Within 4–8 weeks e) After 8 weeks 19. What is the status of your institution? a) Public hospital b) Training and research hospital c) University Hospital d) Private health institution e) others

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

Analysis of anatomical localization and severity of injury in patients with blood transfusion in urban terrain hospital Sami Eksert, M.D.,1 Aytekin Ünlü, M.D.,2 Fevzi Nuri Aydın, M.D.,3 Murtaza Kaya, M.D.,4 Mehmet Burak Aşık, M.D.,5 Ali Kantemir, M.D.,6 Muharrem Öztaş, M.D.,2 Kenan Keklikci, M.D.,7 Ender Sir, M.D.1 1

Department of Anesthesia and Reanimation, Health Sciences University, Gülhane Training and Research Hospital, Ankara-Turkey

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

Department of Biochemistry, Health Sciences University, Dışkapı Training and Research Hospital, Ankara-Turkey

Department of Emergency Medicine, Kütahya Health Sciences University, Kütahya-Turkey

Department of Head and Neck Surgery, Health Sciences University, Gülhane Training and Research Hospital, Ankara-Turkey

Department of Orthopedics and Traumatology, Katip Çelebi University Atatürk Training and Research Hospital, İzmir-Turkey

Department of Orthopedics and Traumatology, Anadolu Medical Center Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Blood loss is the most significant cause of mortality in trauma cases. In injured patients, rapid evaluation and appropriate transfusion is lifesaving. The present study aims to analyze the blood/blood products requirement based on available data and find any associations between the transfusion requirements and injury severity scores (ISS) and anatomical locations of injuries of transfused patients. METHODS: Between 30 July 2014 and 30 July 2016, casualties admitted to the urban terrain hospital (UTH) and transfused at least one unit of red blood cell (RBC) were included. UTH Transfusion Record Notebook data included patients’ age, mechanism and anatomical location(s) of the injury, admission hemoglobin (g/dL) level, injury severity score (ISS), transfused units of erythrocyte suspension (ES), warm fresh whole blood (WFWB), fresh frozen plasma (FFP), and massive transfusion (MT) rate. RESULTS: In this study, all patients were male; the mean age was 28.7±7.8 years. Overall, 59 of 579 (10%) patients were transfused 458 units of RBC (ES+WFWB). Torso (thorax ± abdomen) injury was present in 61% of the casualties who underwent transfusion, and 93% of these patients underwent massive transfusion. In 71% of patients, the ISS was >15, and there was statistically significant high blood/blood products use and MT rate in these patients, respectively (p=0.021, p=0.006). CONCLUSION: Anatomical location of injuries and ISS are valuable in the rapid determining of MT and survival rates of casualties. Especially in torso injuries, bleeding control is difficult and transfusion requirement and mortality rates are high. This study presents the trauma of urban terrain conflict-related transfusion data from a UTH. Keywords: Fresh whole blood; hemorrhage; transfusion; trauma.

INTRODUCTION Hemorrhage is the leading cause of trauma-related mortality in both military and civilian settings.[1,2] Further data stratification shows that 90% of potentially preventable mortalities

are also due to bleeding.[3] Thus, planning for blood and blood component resources for trauma care purposes is inevitably one of the most critical elements for both civilian and military planners. Urban terrain hospitals (UTH) and other institutions in the health system need to reassess their blood

Cite this article as: Eksert S, Ünlü A, Aydın FN, Kaya M, Aşık MB, Kantemir A, et al. Analysis of anatomical localization and severity of injury in patients with blood transfusion in urban terrain hospital. Ulus Travma Acil Cerrahi Derg 2020;26:937-942. Address for correspondence: Sami Eksert, M.D. Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 304 59 07 E-mail: exert79@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(6):937-942 DOI: 10.14744/tjtes.2020.94789 Submitted: 27.01.2020 Accepted: 05.03.2020 Online: 27.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

937

Eksert et al. Analysis of anatomical localization and severity of injury in patients with blood transfusion in UTH

bank capabilities and adequacy of their blood/blood products reserves according to lessons learned from past terrorist attack incidents or military campaigns against those terrorist targets. Trauma and transfusion data derived from recent urban terrain conflict casualties are important in means of evaluations and future estimations of blood transfusion requirements in similar situations. This may enable expedited access of health care professionals to blood bank reserves that were reinforced accordingly. Since 1984, despite the years of fight against terrorism and medical expertise gained during the trauma care of casualties in this period, relatively few scientific analyses on combat injuries have been reported.[4–6] However, after many years of anecdotal trauma transfusions that relied on huge amounts of fresh whole blood in UTHs, only one trauma-transfusion study was reported.[7] Between 2014 and 2016, Şırnak became a center of urban combat against the terrorist organization and Şırnak UTH was located in the middle of this conflict. The present study aims to analyze the blood/blood products consumption based on available data and find any associations between the transfusion requirements and injury severity scores (ISS), and anatomical locations of injuries of transfused patients.

MATERIALS AND METHODS Gülhane Training and Research Hospital Ethics Committee approval (2018/11, 18/235, 16 October 2018) was received for the retrospective descriptive study. This study comprised patients injured during urban combat and admitted to the Şırnak CHS between 01 August 2014 and 01 August 2016. The casualties were the military and the police special operations team personnel and the civilian guards. The UTH had three operating tables, an advanced Intensive Care Unit (ICU), and subspecialty care capabilities. The casualties with severe injuries typically underwent lifesaving interventions, damage control resuscitation, and evacuated to a higher-level military hospital at the earliest convenience. Data were collected from the Blood/Blood Product Transfusion Record Notebook and files of the casualties. The recorded data included the patients’ ID, age, mechanism of injury, anatomical location of the injury, admission hemoglobin (g/dL) level, amount of transfused blood/blood product(s), and early mortality rate. The recorded time to mortality after arrival <24 hours was accepted as early mortality. In addition, injury severity score (ISS) was evaluated and recorded in all transfused patients. ISS is an anatomical scoring system used in patients with multiple injuries. An injury scale score is assigned to each of the six body regions. The scores of the three most severely injured body parts are squared, and the totals are taken to generate the ISS score.[8] 938

In Turkey, blood/blood products are kept in hospitals. A minimum of twenty ES and FFP from all blood groups which were procured from the Turkish Red Crescent were stored properly at Şırnak UTH. On the other hand, warm fresh whole blood (WFWB) was also available and all walking blood (bank) donors were military personnel that complied with donor eligibility criteria according to the National Blood and Blood Products Guide.[9] Blood groups of all possible donors were determined previously. Walking blood donors were gathered for donation at the UTH when required. Microbiological screening tests (HbsAg, anti-HCV, anti-HIV and anti-syphilis Ab) were examined by EIA Acess2 (Beckman Coulter, Brea, CA, USA) and confirmatory blood grouping was performed by the column agglutination technique (DiaClon Bio-Rad, DiaMed GmbH, Cressier FR, Switzerland). In case of emergency blood supply demands, microbiological screening tests were performed using rapid testing kits (Laboquick kits, Koroglu Medical Devices, İzmir, Turkey). Cross-match tests were performed using the indirect antiglobulin test (IAT) gel technique on commercial LISS/ Coombs cards (DiaClon, BioRad, DiaMed GMbH, Cressier FR, Switzerland). In case of unfavourable test results, the untransfused ES was retrieved. O Rh (-) ES and AB (+) FFP was used under contingency situations when blood products were needed for transfusion in less than 15 minutes. As soon as the microbiological screening and cross-match tests results were obtained, transfusion was continued with the patient’s own blood group. WFWB and/or ES+FFP were used and the sequence of the above-mentioned blood/blood products depended exclusively on the availability of blood resources and choice of military medical personnel. Massive transfusion (MT) was defined as transfusion ≥10 units RBCs within 24 hours of admission. None of the patients received tranexamic acid.

Statistical Analysis Data were statistically analyzed using SPSS-22 software (Statistical Package for the Social Sciences, IBM Inc., USA). Continuous data were presented as Mean (±SD) unless otherwise stated. Group differences between the dichotomous and continuous variables were analyzed using independent samples t-test. Categorical variables were analyzed using the chi-squared test and Fischer’s exact test as appropriate. Statistical significance was set at <0.05.

RESULTS In this study, all patients were male, and the mean age was 28.7±7.8 years old. Five hundred and seventy-nine injured patients were admitted to the UTH within the specified date range. The early mortality rate (first 24 hours) was 54.2% (32/59) in the first 24 hours. Forty-three (73%) casualties were wounded with the gunshot and 16 (27%) with exploUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Eksert et al. Analysis of anatomical localization and severity of injury in patients with blood transfusion in UTH

Table 1. Casualty demographics, injury mechanisms, anatomic sites of injury, and distribution of vascular injuries Age (mean±SD), years

28.7±7.8

Early mlortality rate (first 24 hours) Injury Severity Score, (mean±SD)

Head, neck and face injuries; n=14; 23.7%

54.2% (32/59) 20.8±13.1

Mechanism of injury

Gunshot wounds

Explosives

Torso (thorax±abdomen injuries); n=36; 61%

43 (73%) 16 (27%)

Extremity injuries; n=8; 13.6%

SD: Standard deviation.

sives (Table 1). Anatomical sites of injury and distribution of vascular injuries are in Figure 1. Torso (abdomen ± thorax) injuries comprised 36 of 59 (61%) patients. Distribution of casualty blood groups is presented in Figure 2. A+ and B+ were the most common (50.8%, and 22%, respectively) blood types among the transfused casualties.

External (soft tissue) injury; n=1; 1.7%

Figure 1. Anatomical site(s) of injury. 35

The distribution of transfused blood/blood products types is presented in Table 2. MT rates of the overall and transfused patients were 2.4% (14/579) and 23% (14/59), respectively. Overall, 552 units of blood/blood product transfusion were administered to 59/579 (10%) patients. The mean transfused blood units were 7.76±8.45 (min: 1, max: 53). The mean hemoglobin value of the patients who were transfused was 11.4±3.2 g/dL (min: 4.3, max: 16.1) at first admission. In patients with MT, and without MT, the mean (±SD) hemoglobin levels were 9.8±2.5 mg/dL, and 11.8±3.2 mg/dL (p=0.03), respectively. (Table 3) Additionally, torso injuries constituted 93.3% (13/14, p=0.006) of patients that required MT. The rate of MT in thoracic, thoraco-abdominal and abdominal injuries was 35.7%, 35.7% and 21.4%, respectively. The mean ISS was 20.8±13.0 (min: 1, max: 50) and scores >15 indicate a major or severe injury. ISS scores of 42 (71%) patients were >15 and 14 (33.3%) of those severe injuries

n=30 (50.8%)

30 25 20

n=13 (22%)

15 10 5 0

n=6 (10.1%)

n=4 (6.7%)

0–

n=2 (3.3%)

A+

A–

n=3 (5%)

n=1 (1.6%)

B+

B–

AB+

n=0 (0%)

AB–

Figure 2. Blood groups of the patients in this study.

had MT. The association between the MT and ISS scores was statistically significant (p=0.006). A significant but not surprising finding was that ISS >15 patients received significantly more blood/blood product than ISS ≤15 patients (9.3±9.4 vs. 3.7±2.6, p=0.021) (Table 4). No transfusion-related complications were observed.

Table 2. The distribution of transfused blood/blood products types Blood product(s) ES

Casualty number (%)

Overall number of transfused blood products (unit)

15 (25)

31 ES

FFP 0

WFWB

8 (14)

102 WFWB

ES + FFP

1 (1)

7 ES + 5 FFP

WFWB + FFP

14 (24)

130 FWB + 60 FFP

ES + WFWB

14 (24)

48 ES + 82 WFWB

7 (12)

25 ES + 29 FFP + 33 WFWB

59 (100)

552

ES + FFP + WFWB Total

ES: Erythrocyte suspension; FFP: Fresh frozen plasma; WFWB: Warm fresh whole blood.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

939

Eksert et al. Analysis of anatomical localization and severity of injury in patients with blood transfusion in UTH

Table 3. Distribution of the number of transfusions, and admission hemoglobin level

Number of transfused patients (n)

Transfusion rate in all patients (n)

Number of transfused blood units (Mean±SD)

Admission hemoglobin level (mg/dL, Mean±SD)

Non-MT patients (<10 units)

45/59 (77%)

45/579 (7.7%)

5.3±2.7

11.8±3.2

MT patients (≥10 units)

14/59 (23%)

14/579 (2.4%)

18.8±11.2

9.8±2.5

Total 59 (100%) 59/579 (100%) 7.76±8.5

11.4±3.2

MT: Massive transfusion; SD: Standard deviation.

Table 4. Distribution of Injury Severity Score (severe injury).

ISS >15

ISS ≤15

Number of transfused patients

42/59 (71%)

17/59 (29%)

–

Number of MT

14/42 (33%)

0/17 (0%)

0.006

9.3±9.4

3.7±2.6

0.021

Number of transfused blood product units (mean±SD) MT: Massive transfusion; SD: Standard deviation; ISS: Injury Severity Score.

DISCUSSION The primary finding of this study was that the need for MT and the mortality rate was higher as a result of increased blood loss due to difficult bleeding control in thoracic injuries. ISS can provide a reliable prediction of the severity of the injury and the need for MT. Medics performing initial intervention and triage on the battlefield can make a positive contribution to MT and mortality by rapidly assessing the presence of thorax injury and ISS. The data reported in this study may not be easily discussed as comparable (urban combat injury and transfusion) studies are few in the literature. However, combat trauma literature has firmly established the foundations of certain facts on which the authors of this study shall build their arguments. The first and the most notorious fact to emphasize is the early mortality, delayed evacuation and delays in surgical care. Combat support hospitals report conventional battle mortality of 2–4%, although the prehospital mortality was five or 10 times more due to the above delays.[10] Decreasing the transport time from the point of injury to definitive care has been shown to decrease the mortality of noncompressible torso hemorrhage (NCTH- one or more of the thoracic cavity, grade 4 liver, kidney or spleen injury, named torso vessel and pelvic ring fracture) combined with an amputation injury.[11] The mortality rate of NCTH is >85% and 90% of these die in the pre-hospital period.[12] Our UTH was approximately one km from the city center during the urban operations in Şırnak. Casualty transport time was <10 minutes. Thus, it was the authors’ observation that more exsanguinating casualties arrived alive at the UTH. Unsurprisingly, 61% of casualties that reached definitive care at our UTH had NCTH and their mortality rate was 58%. Our overall mortality rate was 54.2%. Combat injuries differ from civilian trauma using explosives and high-ve940

locity missiles designed for maximum damage.[11] This fact is also relevant for urban operations, as reflected by the current study. Explosives were the dominant injury mechanism during military conflicts.[4,13] However, during urban operations, our data show that 73% of casualties were wounded by GSWs. Champion et al.[14] presented the only urban combat-related mortality data. Israeli Defence Forces’ (IDF) most common urban conflict wounding mechanism was also GSWs, their evacuation time averaged 53 minutes, their chest injury rate was 67% and 73% of chest injuries had died. As a result, their exsanguination related mortality rate increased from 41% to 56%, which was a common finding in our study. The mean Hb value of transfused patients may not appear to be too low. However, the Hb values measured in these patients are higher than they actually are due to hemoconcentration in acute blood loss. After acute and severe bleeding, it is generally assumed that Hb and hematocrit do not reflect the estimated blood loss since the passage of fluids through the interstitial space into the vessels is relatively slow.[15] Thus, we performed transfusion according to the injury site and severity of injury regardless of the measured Hb value. Although not sufficient alone, ISS is a scoring method developed to predict mortality. Most trauma studies showed ISS scores correlated with prehospital hypotension or the need for urgent RBC transfusion upon hospital arrival.[16] Our study showed that ISS scores >15 were also associated with MT and a higher amount of RBC transfusion. Severe injuries that require transfusion have an increased mortality rate (range 10–20%).[17] Besides, a retrospective study from US military campaigns in Iraq suggested a significant decrease in mortality when ES, FFP and platelets were initially transfused at a 1:1:1 ratio.[18] Holcomb et al.[19] performed a prospective Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Eksert et al. Analysis of anatomical localization and severity of injury in patients with blood transfusion in UTH

randomized study in civilian trauma patients and showed that a 1:1:1 transfusion ratio resulted in better hemostasis and decreased 24-hour mortality; however, the differences in 24hour and 30-day survival was not statistically significant. In our cases, our data show that only 25% of erythrocytes were used (at a ratio of 1:0.8) for trauma patients; WFWB was preferred in the majority of cases. No platelet suspensions were available during the operations, which may have affected the type of blood/blood product use. MT is required in exsanguinating patients, which has been estimated to occur in 3% to 5% of civilians and 8% to 10% of military trauma patients. Mortality in MT patients is the most common cause of death within 1-hour of arrival.[9] The mortality rate of these trauma casualties range between 40% to 60%, and they are reported to consume >70% of total RBCs transfused. In our study, the overall MT rate was 2.4%, but they only used 57% of all transfused RBCs. This relatively lower proportion of overall RBCs used in MT may be because some patients expired very early upon arrival that MT protocol could not be initiated. Ramsey reviewed 24 medical reports on mass casualty events after 1980 for transfused RBCs.[20] The mean RBCs and FFP use per admitted patient was 3 and 2.1 units, respectively. They suggested that the number of patients might be useful for estimating the blood/blood product needs, especially in terrorist bombings. Although our mean transfused RBCs were 7.7 units, which was not surprisingly high as military trauma creates more severe injuries, the authors of this study agree with Ramsey’s RBC need estimation method. Despite the paucity of trauma data-driven studies in Turkey, injury prevention, control of compressible blood losses using modern military tourniquets[21] expedited transport to military treatment facilities, early resuscitation of ongoing hemorrhage by blood and blood products,[17,22] and increasing the national transfusion capabilities by different blood/blood products[23,24] have become the primary focus of Turkish trauma system. These and other ongoing efforts to improve the Turkish trauma system need to be implemented to increase the preparedness levels for national security protection. This study has inherent limitations. Our data lack blood pressure measurements, standard transfusion triggers, blood gas analyses, time to transport after injury, follow up after medical evacuation to a higher level center. Additionally, the number of cases in this retrospective descriptive study is small, as it includes cases limited to a two-year tenure. However, to our knowledge, this is the first study on transfused urban combat casualties in Turkey, and it will make a significant contribution to the literature.

ed with high MT and mortality rates. Although larger series are obviously needed to obtain a brighter picture of such injuries, we can roughly estimate the significance of the ISS score and the presence of torso injury. Thus, medical personnel will be alerted for immediate and accurate intervention to these injuries. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Holcomb JB, del Junco DJ, Fox EE, Wade CE, Cohen MJ, Schreiber MA, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg 2013;148:127–36. 2. Buehner MF, Eastridge BJ, Aden JK, DuBose JJ, Blackbourne LH, Cestero RF. Combat Casualties and Severe Shock: Risk Factors for Death at Role 3 Military Facilities. Mil Med 2017;182:e1922–8. 3. Eastridge BJ, Mabry RL, Seguin P, Cantrell J, Tops T, Uribe P, Mallett O, et al. Death on the battlefield (2001-2011): implications for the future of combat casualty care. J Trauma Acute Care Surg 2012;73:S431–7. 4. Ünlü A, Cetinkaya RA, Ege T, Ozmen P, Hurmeric V, Ozer MT, et al. Role 2 military hospitals: results of a new trauma care concept on 170 casualties. Eur J Trauma Emerg Surg 2015;41:149–55. 5. Aşık MB, Akay S, Eksert S. Analyses of combat-related injuries to maxillofacial and cervical regions and experiences in an operational field hospital. Ulus Travma Acil Cerrahi Derg 2018;24:56–60. 6. Güven HE, Bilge S, Aydın AA, Eryılmaz M. Comparison of the non-mortal gunshot and handmade explosive blast traumas during a low-intensity conflict on urban terrain. Turk J Surg 2018;34:221–4. 7. Eryılmaz M, Tezel O, Taş H, Arzıman I, Oğünç GI, Kaldırım U, et al. The relationship between Injury Severity Scores and transfusion requirements of 108 consecutive cases injured with high kinetic energy weapons: a tertiary center end-mode mortality analysis. Ulus Travma Acil Cerrahi Derg 2014;20:39–44. 8. Javali RH, Krishnamoorthy, Patil A, Srinivasarangan M, Suraj, Sriharsha. Comparison of Injury Severity Score, New Injury Severity Score, Revised Trauma Score and Trauma and Injury Severity Score for Mortality Prediction in Elderly Trauma Patients. Indian J Crit Care Med 2019;23:73– 7. 9. Nunez TC, Voskresensky IV, Dossett LA, Shinall R, Dutton WD, Cotton BA. Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)?. J Trauma 2009;66:346–52. 10. Bellamy RF. Combat trauma overview. In: Zatchuk R, Grande CM, editors. Textbook of Military Medicine, Anesthesia and Perioperative Care of the Combat Casualty. Falls Church, VA: Office of the Surgeon General, United States Army;1995.p.1–42.

Conclusion

11. Maddry JK, Perez CA, Mora AG, Lear JD, Savell SC, Bebarta VS. Impact of prehospital medical evacuation (MEDEVAC) transport time on combat mortality in patients with non-compressible torso injury and traumatic amputations: a retrospective study. Mil Med Res 2018;5:22.

Torso injuries that occurred in the combat field are associat-

12. Morrison JJ, Stannard A, Rasmussen TE, Jansen JO, Tai NR, Midwinter

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

941

Eksert et al. Analysis of anatomical localization and severity of injury in patients with blood transfusion in UTH MJ. Injury pattern and mortality of noncompressible torso hemorrhage in UK combat casualties. J Trauma Acute Care Surg 2013;75:S263–8.

2012;73:S445–52.

13. Holcomb JB, McMullin NR, Pearse L, et al. Causes of death in U.S. Special Operations Forces in the global war on terrorism: 2001-2004. Ann Surg 2007;245:986–91.

19. Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA 2015;313:471–82.

14. Champion HR, Bellamy RF, Roberts CP, Leppaniemi A. A profile of combat injury. J Trauma 2003;54:S13–9.

20. Ramsey G. Blood component transfusions in mass casualty events. Vox Sang 2017;112:648–59.

15. Ryan ML, Thorson CM, Otero CA, Vu T, Schulman CI, Livingstone AS, et al. Initial hematocrit in trauma: a paradigm shift?. J Trauma Acute Care Surg 2012;72:54–60.

21. Unlu A, Kaya E, Guvenc I, Kaymak S, Cetinkaya RA, Lapsekili EO, et al. An evaluation of combat application tourniquets on training military personnel: changes in application times and success rates in three successive phases. J R Army Med Corps 2015;161:332–35.

16. Huang GS, Dunham CM. Mortality outcomes in trauma patients undergoing prehospital red blood cell transfusion: a systematic literature review. Int J Burns Trauma 2017;7:17–26. 17. Shackelford SA, Del Junco DJ, Powell-Dunford N, Mazuchowski EL, Howard JT, Kotwal RS, et al. Association of Prehospital Blood Product Transfusion During Medical Evacuation of Combat Casualties in Afghanistan With Acute and 30-Day Survival. JAMA 2017;318:1581–91. 18. Pidcoke HF, Aden JK, Mora AG, Borgman MA, Spinella PC, Dubick MA, et al. Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased plasma and platelet use correlates with improved survival. J Trauma Acute Care Surg

22. Unlu A, Yilmaz S, Yalcin O, Uyanik M, Petrone P, Cetinkaya RA, et al. Bringing Packed Red Blood Cells to the point of Combat Injury: Are we there yet? Turk J Haematol 2018;35:185–91. 23. Cetinkaya RA, Yilmaz S, Eker I, Ünlü A, Uyanik M, Tapan S, et al. In vitro efficacy of frozen erythrocytes: implementation of new strategic blood stores to alleviate resource shortage (issue revisited). Turk J Med Sci 2015;45:638–43. 24. Yılmaz S, Çetinkaya RA, Eker İ, Ünlü A, Uyanık M, Tapan S, et al. Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey. Turk J Haematol 2016;33:28–33.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Saha hastanesinde kan transfüzyonu uygulanan hastalarda yaralanma şiddeti ve anatomik lokalizasyonunun analizi Dr. Sami Eksert,1 Dr. Aytekin Ünlü,2 Dr. Fevzi Nuri Aydın,3 Dr. Murtaza Kaya,4 Dr. Mehmet Burak Aşık,5 Dr. Ali Kantemir,6 Dr. Muharrem Öztaş,2 Dr. Kenan Keklikci,7 Dr. Ender Sir1 Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Anabilim Dalı, Ankara Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Ankara 3 Sağlık Bilimleri Üniversitesi, Dışkapı Eğitim ve Araştırma Hastanesi, Biyokimya Anabilim Dalı, Ankara 4 Kütahya Sağlık Bilimleri Üniversitesi, Acil Tıp Anabilim Dalı, Kütahya 5 Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Kulak Burun Boğaz Cerrahisi Kliniği, Ankara 6 Katip Çelebi Üniversitesi Atatürk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, İzmir 7 Anadolu Sağlık Merkezi Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul 1 2

AMAÇ: Travma olgularında en önemli mortalite nedeni kanamadır. Yaralıların hızlı değerlendirmesi ve uygun transfüzyonu hayat kurtarıcıdır. Bu çalışmanın amacı, mevcut verilere dayanarak, kan/kan ürünü transfüzyon deneyimlerini analiz etmek, transfüzyon gereksinimi ile yaralanma şiddeti skoru (injury severity score-ISS), ve yaralanma bölgesinin anatomik yerleşimi arasında ilişkiyi değerlendirmektir. GEREÇ VE YÖNTEM: Çalışmaya 30 Temmuz 2014–30 Temmuz 2016 tarihleri arasında, saha hastanesine başvuran ve en az bir ünite kan/kan ürünü transfüzyonu yapılan yaralılar alındı. Hastane transfüzyon kayıt defterinden, hastaların yaşı, yaralanma mekanizması, yaralanmanın anatomik yerleşimi, hastaneye kabul hemoglobin (g/dL) değeri, ISS, transfüze edilmiş eritrosit süspansiyonu, sıcak taze tam kan, taze donmuş plazma gibi kan ürünleri miktarı ve masif transfüzyon (MT) oranı ile ilgili veriler elde edildi. BULGULAR: Tüm hastalar erkekti, ortalama yaş 28.7±7.8 yıl idi. Toplamda 579 hastadan 59’una (%10) 458 ünite RBC (ES+WFWB) transfüzyonu yapıldı. Transfüzyon uygulanan yaralıların %61’inde gövde (toraks±karın) yaralanması vardı ve bu hastaların %93’üne masif transfüzyon uygulandı. Hastaların % 71’inde ISS >15 idi ve bu hastalarda istatistiksel olarak anlamlı yüksek kan/kan ürünleri kullanımı ve MT oranı vardı (p=0.021, p=0.006). TARTIŞMA: Yaralanmaların ve ISS’nin anatomik yeri, MT’nin hızlı bir şekilde belirlenmesinde ve kazazedelerin hayatta kalma oranlarında değerlidir. Özellikle gövde yaralanmalarında kanama kontrolü zordur ve transfüzyon gereksinimi ve mortalite oranları yüksektir. Ayrıca bu makale bir saha hastanesindeki, kentsel arazi çatışmasıyla ilgili transfüzyon verilerini sunmaktadır. Anahtar sözcükler: Kanama; taze tam kan; transfüzyon; travma. Ulus Travma Acil Cerrahi Derg 2020;26(6):937-942

942

doi: 10.14744/tjtes.2020.94789

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ORIGIN A L A R T IC L E

The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations Mustafa Yalın, M.D.,1 Furkan Çağlayan Aslantaş, M.D.,2 Altuğ Duramaz, M.D.,3 Mustafa Gökhan Bilgili, M.D.,3 Emre Baca, M.D.,3 Alican Koluman, M.D.3 1

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

Department of Orthopedics and Traumatology, Ardahan State Hospital, Ardahan-Turkey

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

ABSTRACT BACKGROUND: The ankle fracture-dislocations are a significant traumatic incident for the bone and the soft tissue surrounding the ankle. Bone stabilization, joint immobilization, anatomic reduction and intervention for soft tissue protection should be performed as early as possible. The present study aims to determine the frequency of major comorbidities that can be seen after surgery in patients with ankle fracture-dislocations and the relationship between the trauma mechanism and clinical status with these comorbidities. METHODS: Thirty-eight patients (25 males, 13 females) who underwent surgery with ankle fracture-dislocations between May 2014 and February 2017 were evaluated retrospectively in this study. All patients were evaluated clinically and radiologically at least 24 months postoperatively. Arthrosis, synostosis, presence of the chondral lesion and AOFAS scores were detected for all patients. RESULTS: Mean AOFAS score was lower in open ankle fracture-dislocations than in closed dislocations (p=0.044). An accompanying osteochondral lesion (OCL) and increased patient age were found to be strongly associated with the development of arthrosis (p=0.005 and p=0.017; respectively). Four of 29 patients who received primer definitive surgery and four of nine patients who received step-by-step surgery had poorly calculated AOFAS scores (p=0.071). There was no significant relationship between dislocation direction and AOFAS scores (p=0.087). CONCLUSION: Clinical and functional results were found to be worse in patients with open ankle fractures, the rate of arthrosis increased with age, and the use of syndesmosis screw had a positive but not a statistically significant effect on clinical and functional outcomes. Keywords: Ankle arthrosis; ankle fracture-dislocation; ankle osteochondral lesion; syndesmosis fixation.

INTRODUCTION Ankle fracture-dislocations are a medical emergency encountered by foot-ankle surgeons. Serious complications may occur if the ankle mortise is not assessed and reduced in time.[1] Emergency reduction of the ankle fracture-dislocations reduces post-injury fatigue, prevents more damage to the articular cartilage and decreases pain in the ankle.[2] However, incorrect and inadequate reduction maneuvers may cause tibial, fibu-

lar and talar chondral injuries. The literature has shown that chondral injuries are very common in acute ankle fractures.[3] Ankle fracture-dislocations are often observed in young men after high-energy trauma, such as motor vehicle accidents or as a result of sports injuries.[4,5] Low energetic, rotational ankle fracture-dislocations have been reported less frequently in the literature.[6] Open ankle fractures are observed with complications, such as amputation, infection and nonunion that threaten the extremity and which can be a devastating event.[7]

Cite this article as: Yalın M, Aslantaş FÇ, Duramaz A, Bilgili MG, Baca E, Koluman A. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations. Ulus Travma Acil Cerrahi Derg 2020;26:943-950. Address for correspondence: Altuğ Duramaz, M.D. Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul, Turkey Tel: +90 212 - 414 71 71 E-mail: altug.duramaz@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(6):943-950 DOI: 10.14744/tjtes.2020.35392 Submitted: 07.11.2019 Accepted: 24.02.2020 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

943

YalÄąn et al. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations

The ankle fracture-dislocations are a considerable traumatic incident for the bone and the soft tissue surrounding the ankle. Bone stabilization, joint immobilization, anatomic reduction and intervention for soft tissue protection should be performed as early as possible.[8] The management of patients with ankle fracture-dislocations is challenging because of the deterioration of ankle mortise and the possibility of instability.[9] This study aimed to determine the frequency of major comorbidities that can be seen after surgery in patients with ankle fracture-dislocations and the relationship between the trauma mechanism and clinical status with these comorbidities. We hypothesized that clinical scores would worsen and complications would increase depending on the type of fracture and dislocation direction, especially in the presence of concomitant chondral injury and ligament injury requiring repair.

MATERIALS AND METHODS After the local ethical approval (IRB protocol code: 2017/430, application ID: 2017-18-30) was obtained, thirty-eight patients (25 males, 13 females) who underwent surgery with an ankle fracture-dislocation between May 2014 and September 2017 were retrospectively evaluated in this study. Patients older than 18 years, no previous ankle injury, follow-up >24 months, no other concurrent injuries on the same lower limb were included in this study. The exclusion criteria were insufficient file records, previous foot and ankle trauma history, follow-up <24 months, diabetes mellitus, peripheral artery disease, and psychiatric disorders. Before the reduction of the dislocated ankle, anteroposterior (AP) and lateral ankle X-rays were routinely performed. Ankle AP and lateral X-rays and CT were also re-evaluated after the reduction. The dislocations which could not be reducted, patients who could not be examined due to patient incompatibility, and patients with suspected vascular injury were performed to reduction and external fixation in the operating room as soon as possible. The decision of the time of definitive treatment for patients who underwent temporary surgery was based on the wrinkle test and the wound status if there was an open fracture-dislocation. MRI display was performed in the postoperative period to investigate the talus osteochondral lesions. MRI was used after an average follow-up period (six to eight months after surgery) to study the incidence of talus OCL in the present study. MRI was reported by an independent radiologist for each patient. Thirty-eight patients were followed clinically and radiologically at least 24 months (follow-up between 24 and 48 months) postoperatively. Radiologically, ankle arthrosis was evaluated on the standard ankle X-rays using the Kellgren-Lawrence (K-L) scale, which is the most frequently used scale for the classification of arthrosis. The K-L scale, which scale was chosen by the World Health Organization as the accepted reference standard that consists of a physician-based assessment of four radiological features, including osteophyte formation, 944

joint space narrowing, the existence of cysts in subchondral bone, and bone end sclerosis.[10] The K-L scale has comparable inter- and intra-observer reliability, as well as similar correlation coefficients, in comparing radiographic classification to arthroscopic findings as with other grading systems. [11] In some studies, it was found that the Kellgren-Lawrence scale was associated with clinical outcomes, unlike the other scales, with increasing Kellgren-Lawrence scores, all clinical scores decreased, more pain and more disability were noted. [12] Grade 3 is characterized by multiple osteophytes, narrowing of joint space, deformity, and sclerosis at bone margins and grade 4 is characterized by large osteophytes, severe narrowing of joint space, severe sclerosis and obvious deformities at bone margins. In the present study, grade 3 and grade 4 arthritis were considered as the presence of arthrosis. AP, lateral and mortis X-rays of the ankle of patients were evaluated in three groups as non-synostosis, incomplete bone bridge and complete synostosis in the current study. Patients with incomplete bone bridge and complete synostosis formed the synostosis group. The functional assessments were based on the American Orthopedic Foot and Ankle Score (AOFAS) protocol. The AOFAS protocol is an assessment based on clinical parameters and does not include radiological parameters. Clinical parameters, including pain, functional assessment and alignment, are numerically assessed and reported as good or poor results. Patients whose score above 70 out of 100 are considered good results and patients whose scores below 70 are considered poor results.[13]

Statistical Analysis Descriptive statistics (mean, standard deviation, minimum, median, maximum) were used to describe continuous variables. The relationship between the two independent variables was investigated using the Mann-Whitney U test. Chi-Square (or Fisher Exact test at appropriate locations) was used to examine the relationship between categorical variables. The statistical significance level was determined as p<0.05. The statistical calculation used for the analysis of each parameter was indicated as an upper case of the p value in the tables. Analyses were performed using the MedCalc Statistical Software version 12.7.7 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2013)

RESULTS The descriptive features of the patients are presented in Table 1. Male sex, high-energy trauma, Weber type C fracture, primary (definitive) surgery, closed fracture and good AOFAS score was the prominent demographic features. Closed fractures showed a statistically significant difference concerning fracture type according to the AOFAS score (p=0.044) (Table 2). The AOFAS score was poor in four of nine patients treated with temporary surgery, whereas the AOFAS score was poor in four of 29 patients treated with primary definitive surgery. Although no significant difference was found conUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Yalın et al. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations

Table 1. Demographic characteristics of the patients

Min-Max (Median)

Mean±SD 33.9±14.6

Age (years)

15–74 (31)

Time to surgery (days)

0–12 (5)

4.7±3.2

AOFAS Score

44–100 (80)

80.9±12.7

Body mass index (kg/m2)

21–37 (27)

28.02±4.05

Follow-up

24–48 (33)

33.6±10.8

n %

Gender

Male

25 65.8

Female

13 34.2

Trauma mechanism

High energy

68.4

Low energy

31.6

Deltoid repair

Yes

15.8

84.2

Direction of dislocation

13.2

13 34.2

Lateral

Medial

3 7.9

Posterior

17 44.7

Lauge Hansen Classification

PER

15 39.5

23.7

4 10.5

SER

10 26.3

Weber Classification

Type A

2.6

Type B

13.1

Type C

84.2

Treatment method

Temporary surgery

23.7

Primary/definitive 29 76.3

Smoking

63.2

Yes

36.8

Alcohol

76.3

Yes

23.7

Type of fracture

Open

21.1

Closed

78.9

Presence of arthrosis

57.9

Yes

42.1

Presence of chondral injury

78.9

Yes

21.1

Synostosis

86.8

Yes

13.2

Syndesmotic screw

55.3

Yes

44.7

Posterior stabilization

52.6

Yes

47.4

Body mass index (kg/m )

Not obese (<30)

73.7

Obese (>30)

26.3

AOFAS

Poor

8 21.1

Good

30 78.9

AOFAS: The American Orthopaedic Foot and Ankle Society, PA: Pronation-adduction, PER: Pronation-external rotation, SA: Supination-adduction, SER: Supination-external rotation.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

945

Yalın et al. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations

Table 2. The relationship between the presence of arthrosis and variables and the comparison of the variables concerning effects on AOFAS scores

Presence of Arthrosis

No Yes

Mean±SD Mean±SD Median (Min.-Max.) Median (Min.-Max.)

Age (years) Follow-up (months)

29.1±11.9 26 (19–60) 30.4±8.6 28 (25–39)

40.6±15.6 38 (21–74) 32±7.3 (26–41)

0.017

Yes

n (%)

14 (63.6) 8 (36.4) 3 (13.6) 9 (40.9) 1 (4.5) 9 (40.9) 21 (95.5) 1 (4.5) 12 (54.5) 10 (45.5) 17 (77.3) 5 (22.7)

11 (68.8) 5 (31.3) 2 (12.5) 4 (25) 2 (12.5) 8 (50) 9 (56.3) 7 (43.8) 8 (50) 8 (50) 11 (68.8) 5 (31.3)

Gender Direction of dislocation Chondral lesion presence Posterior stabilization BMI (kg/m2)

Male Female Anterior Lateral Medial Posterior No Yes No Yes Not obese (<30) Obese (>30)

Age (years) Time to surgery (days) BMI (kg/m2)

AOFAS Score

0.731

0.005 1.00 0.713

Poor Good Mean±SD Mean±SD Median (Min.-Max.) Median (Min.-Max.) 36.5±20.5 31 (21–74) 3.5±2.7 4 (0–7) 28.5±3.2 27 (26–35)

33.3±12.9 0.986 31 (19–63) 5±3.2 0.297 5 (0–12) 27.9±4.3 0.449 26.5 (21–37)

Poor

Good

n (%)

2 (25) 1 (12.5) 2 (25) 3 (37.5) 4 (50) 4 (50) 8 (100) 0 (0) 1 (12.5) 7 (87.5)

3 (10) 12 (40) 1 (3.3) 14 (46.7) 4 (13.3) 26 (86.7) 25 (83.3) 5 (16.7) 16 (53.3) 14 (46.7)

Anterior Lateral Medial Posterior Open Closed No Yes No Yes

1.00

Direction of dislocation Type of fracture Synostosis Syndesmotic screw

0.472

0.087

0.044 0.563 0.053

AOFAS: The American Orthopaedic Foot and Ankle Society; BMI: Body mass index; SD: Standard deviation. p1: Mann–Whitney U test, p2: Chi-square test (Fisher’s test).

946

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

YalÄąn et al. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations

cerning the AOFAS scores according to the surgery method, the mean AOFAS score was found to be remarkably high in the primary definitive surgery groups (p=0.071). It was noteworthy that the syndesmotic screw was used with a higher percentage in patients with poor scores although the use of syndesmotic screw did not differ significantly on AOFAS scores (p=0.053). There was no statistically significant difference concerning synostosis according to the use of syndes-

(a)

(b)

motic screw (Fig. 1a-e). Ankle arthrosis was seen in seven of eight patients with chondral lesions and nine of 30 patients without chondral lesions (Fig. 2a-d). Also, one patient had to have talectomy (Figs. 3a-f). A statistically significant correlation was observed between the presence of a chondral lesion and the occurrence of arthrosis (p=0.005). A strong relationship was found between increased patient age and the development of arthrosis (p=0.017) (Table 2).

(d)

(e)

(c)

Figure 1. 29-year-old male, admission due to the motorcycle accident. (a) Plain radiographs show the left ankle fracture dislocation, (b) CT sections show the medial and posterior malleolus fractures and fibular distal diaphyseal fractures accompanying the left ankle lateral dislocation, (c) Temporary fixation was achieved with a monoplanar external fixator and one K-wire. Definitive fixation was applied on the 13th day after the trauma using two malleolar screws and syndesmosis screw. (d) Plain radiographs obtained 28 months after treatment show the synostosis of the distal tibiofibular joint, (e) CT sections show the posttraumatic arthritis, joint narrowing and the synostosis of the distal tibiofibular joint.

(a)

(b)

(d)

(c)

Figure 2. 34-year-old female, admission due to pedestrian crash. (a) Plain radiographs show the right ankle fracture dislocation, (b) CT sections show medial malleolus fracture and fibula diaphyseal fracture accompanying the right ankle anterior dislocation. Definitive treatment was performed on the second day of the trauma using tubular plate-screw fixation for fibula fracture and two malleolar screws for medial malleolus. (c) Plain radiographs obtained 43 months after treatment show the severe arthrosis of the tibiotalar joint, (d) CT sections show the severe posttraumatic tibiotalar arthritis and joint narrowing of the tibiotalar joint.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

947

YalÄąn et al. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations

(a)

(e)

(b)

(c)

(d)

(f)

Figure 3. 48-year-old male, admission after falling from a height. (a) Plain radiographs show the right ankle fracture-dislocation, (b) CT sections show the comminuted talus fracture and syndesmotic injury accompanying the right talus posterior dislocation, (c) Definitive treatment was emergently achieved with talectomy, syndesmotic fixation and deltoid ligament repair using a bone anchor-screw. (d) Plain radiographs obtained 39 months after treatment show the severe arthrosis of the tibiotalar joint, (e) CT sections show the distal tibiofibular osteophytes and tibio-calcaneal joint, (f) the patient has ankle joint range of motion to allow daily life activities.

DISCUSSION The most important findings of the present study were that (1) the clinical and functional results of the open ankle fracture-dislocations were lower, (2) the talar chondral lesion formed after the ankle fracture dislocation led to the arthrosis, (3) the arthrosis rate increased with the older patient age. Previous papers stated that open ankle fractures had lower AOFAS scores than closed fractures.[14,15] In the current study, functional and clinical outcomes of patients with closed fractures were found to be higher than patients with open fracture and our study supports the literature. Khan et al.[16] compared external fixator and open reduction internal fixation (ORIF) in open ankle injuries and encountered a deep infection requiring an implant extraction in four cases in the ORIF group, one case of deep vein thrombosis in the external fixator group, one case of necrosis of distal fibula end. Fewer infectious findings have also occurred in the external fixator group than plate application in the study of Pedrini at el.[17] In our study, only one superficial tissue infection and one deep tissue infection that was required patient debridement therapy were observed. In one patient, arthroscopic debridement was performed due to the intensive synovitis tissue formed after ORIF. Post-traumatic talectomy was performed in one patient. Vacuum-assisted closure (VAC) treatment due to open wound formed independently of the incision field was applied in two patients, and then skin grafts were applied to those two patients by plastic surgery. The results of AOFAS scores of patients who had temporary and primer definitive treatment were compared in the present study. No statistically significant difference was found concerning thetreatment method according to AOFAS scores, but the AOFAS 948

scores of patients treated with primary definitive treatment were remarkably high (p=0.071). The number of studies that had a long-term follow-up of the ankle arthrosis (more than 10 years) after malleolar fractures are very rare and most of the relevant studies have examined one or two factors in a small group.[18] After malleolar fractures, there are some situations in which the risk of ankle arthrosis is high. These situations are increased age,[19] fracture severity,[20] the presence and localization of cartilage lesions, especially medial malleolus,[21] fracture reduction quality and the presence of fracture-dislocation. In the present study, there was a strong correlation between patient age and the presence of arthrosis, and the incidence of arthrosis in older ages was high (p=0.017). LĂźbbeke et al.[22] stated that Weber Type C injuries, being over 30 years old at the time of injury, being obese or overweight at the time of injury and having a long follow-up period from the surgery are closely related to the development of arthrosis. In the current study, no statistically significant difference was found concerning fracture type, presence of obesity and duration of follow-up period according to the presence of arthrosis. The reason is that the number of obese patients in our study was limited, and the follow-up period was relatively short (at least 24 months and average 33.6 months) to evaluate the presence of arthrosis. Stufkens et al.[21] noted that the most significant cause of arthrosis development was malunion after an ankle fracture and the importance of correct reduction and fixation was pointed out. Varus/valgus alignment of the distal tibia, ligament injury-causing ligamentous instability, and arthrofibrosis development are also important reasons for ankle osteoarthritis. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Yalın et al. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations

Also, Regan et al.[23] emphasized that a talus OCD developed during injury may lead to late posttraumatic arthrosis. In our study, a statistically significant correlation was shown between the presence of a chondral lesion and the development of arthrosis (p=0.005). However, one of the disadvantages of our study was the lack of treatment of chondral lesions that were found due to the descriptive and retrospective nature. When a syndesmotic injury is detected, the importance of using trans-syndesmotic screws in treatment has been previously pointed out.[24] However, syndesmotic screws may occasionally cause additional morbidity.[25] Tibiofibular fixation may block normal ankle motion and rigid fixation may lead to tibiofibular ligament injury.[25,26] Screws may break after a certain period of loading and may cause chronic pain in the inferior tibiofibular joint.[26] In the present study, all patients with syndesmosis injury (revealed by intraoperative fluoroscopic stress X-ray) were fixed with trans-syndesmotic screws. The use of the syndesmotic screw was not obtained a statistically significant difference concerning AOFAS scores, but it was found that the application of syndesmotic screw was moderately correlated with high AOFAS scores (p=0.053). Marvan et al.[27] found that the rate of synostosis in men was significantly higher. Another parameter that is statistically significant in the same study is the rate of synostosis seen after Weber Type B fractures is 8% and after Weber Type C fractures are 17%. They have also argued that the use of the syndesmotic screw is a powerful cause for the development of synostosis. Previous studies reported that the rate of synostosis after Weber Type C fractures was significantly higher than the rate of synostosis after Weber Type B fractures.[28,29] In addition, Hinds et al.[29] emphasized that posterior malleolar osteosynthesis or PITFL repair may be necessary and sufficient in the treatment of syndesmotic damage. They also stated that the use of a syndesmotic screw, the presence of male gender and a history of tibiotalar dislocation play an important role in the development of distal tibiofibular synostosis. In the present study, no statistically significant difference was found concerning sex, Weber classification, and presence of syndesmotic screws. This may occur since the number of patients with synostosis is not large enough to produce a statistical result. The limitations of this study were retrospective design, small sample size, lack of randomization, and relatively short follow-up, especially for the assessment of ankle arthrosis. On the other hand, the strengths of this study were to evaluate the relationship between the direction of dislocation, acute repair of accompanying ligament injury, different fracture classifications, different treatment methods (temporary or primary) and complications. In conclusion, clinical and functional results were found to be worse in patients with open ankle fractures and with the presence of chondral lesion due to the initial trauma. Also, the rate of arthrosis increased with older ages. We should note that surgeons should be more careful and alert about chondral lesions formed during the trauma and should be Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

more intensive about the treatment of them. Although a good surgery and treatment are performed, the patients should be informed in detail that the poor results may occur. Ethics Committee Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.Y., M.G.B.; Design: M.Y., M.G.B.; Supervision: A.D., M.G.B.; Resource: M.Y., F.Ç.A.; Materials: M.Y., A.K., E.B.; Data: M.Y., A.K., E.B; Analysis: A.D., M.G.B.; Literature search: M.Y., F.Ç.A., A.D.; Writing: M.Y., A.D.; Critical revision: A.D. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Keany JE, McKeever D. Ankle dislocation in emergency medicine. Available from: http://emedicine.medscape.com/article/823087-overview. Accessed October 29, 2012. 2. D’Angelantonio A 3rd, Malay DS, Contento R, Winner R. Instructional technique guide: closed reduction of the supination-eversion Stage IV (Weber Type B) ankle fracture. J Foot Ankle Surg 2009;48:394–7. 3. Leontaritis N, Hinojosa L, Panchbhavi VK. Arthroscopically detected intra-articular lesions associated with acute ankle fractures. J Bone Joint Surg Am 2009;91:333–9. 4. Southerland JT. Mc Glamry’s Comprehensive Textbook of Foot and Ankle Surgery, 4th Edition. Lippincott Williams & Wilkins; 2013. 5. Karampinas PK, Stathopoulos IP, Vlamis J, Polyzois VD, Pneumatikos SG. Conservative treatment of an anterior-lateral ankle dislocation without an associated fracture in a diabetic patient: a case report. Diabetic Foot Ankle 2012;3:1–5. 6. Wilson AB, Toriello EA. Lateral rotatory dislocation of the ankle without fracture. J Orthop Trauma 1991;5:93–5. 7. Ye T, Chen A, Yuan W, Gou S. Management of grade III open dislocated ankle fractures: combined internal fixation with bioabsorbable screws/ rods and external fixation. J Am Podiatr Med Assoc 2011;101:307–15. 8. Høiness P, Strømsøe K. The influence of the timing of surgery on soft tissue complications and hospital stay. A review of 84 closed ankle fractures. Ann Chir Gynaecol 2000;89:6–9. 9. Ross A, Catanzariti AR, Mendicino RW. The hematoma block: a simple, effective technique for closed reduction of ankle fracture dislocations. J Foot Ankle Surg 2011;50:507–9. 10. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957;16:494–502. 11. Moon JS, Shim JC, Suh JS, Lee WC. Radiographic predictability of cartilage damage in medial ankle osteoarthritis. Clin Orthop Relat Res 2010;468:2188–97. 12. Holzer N, Salvo D, Marijnissen AC, Vincken KL, Ahmad AC, Serra E, et al. Radiographic evaluation of posttraumatic osteoarthritis of the ankle: the Kellgren-Lawrence scale is reliable and correlates with clinical symptoms. Osteoarthritis Cartilage 2015;23:363–9. 13. Carr JB. Malleolar Fractures and Soft Tissue Injuries of the Ankle. In:

949

Yalın et al. The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations Browner B, Jupiter BJ, Levin A, Jupiter J, Trafton GP, Krettek C, editors. Skeletal Trauma. 3rd edition, Philadelphia, USA: W&B Saunders; 2003.p.2307–74. 14. Klammer G, Kadakia AR, Joos DA, Seybold JD, Espinosa N. Posterior pilon fractures: a retrospective case series and proposed classification system. Foot Ankle Int 2013;34:189–99. 15. Xu HL, Li X, Zhang DY, Fu ZG, Wang TB, Zhang PX, et al. A retrospective study of posterior malleolus fractures. Int Orthop 2012;36:1929–36. 16. Khan U, Smitham P, Pearse M, Nanchahal J. Management of severe open ankle injuries. Plast Reconstr Surg 2007;119:578–89. 17. Pedrini G, Cardi M, Landini A, Strada G. Management of severe open ankle-foot trauma by a simple external fixation technique: an alternative during war and in resource-poor and low-technology environments. J Orthop Trauma 2011;25:180–7. 18. Stufkens SA, van den Bekerom MP, Kerkhoffs GM, Hintermann B, van Dijk CN. Long-term outcome after 1822 operatively treated ankle fractures: a systematic review of the literature. Injury 2011;42:119–27. 19. Horisberger M, Valderrabano V, Hintermann B. Posttraumatic ankle osteoarthritis after ankle-related fractures. J Orthop Trauma 2009;23:60–7. 20. Beris AE, Kabbani KT, Xenakis TA, Mitsionis G, Soucacos PK, Soucacos PN. Surgical treatment of malleolar fractures. A review of 144 patients. Clin Orthop Relat Res 1997;(341):90–8. 21. Stufkens SA, Knupp M, Horisberger M, Lampert C, Hintermann B. Cartilage lesions and the development of osteoarthritis after internal fixation of ankle fractures: a prospective study. J Bone Joint Surg Am 2010;92:279–86.

22. Lübbeke A, Salvo D, Stern R, Hoffmeyer P, Holzer N, Assal M. Risk factors for post-traumatic osteoarthritis of the ankle: an eighteen year follow-up study. Int Orthop 2012;36:1403–10. 23. Regan DK, Gould S, Manoli A 3rd, Egol KA. Outcomes Over a Decade After Surgery for Unstable Ankle Fracture: Functional Recovery Seen 1 Year Postoperatively Does Not Decay With Time. J Orthop Trauma 2016;30:e236–41. 24. Xenos JS, Hopkinson WJ, Mulligan ME, Olson EJ, Popovic NA. The tibiofibular syndesmosis. Evaluation of the ligamentous structures, methods of fixation, and radiographic assessment. J Bone Joint Surg Am 1995;77:847–56. 25. Peter RE, Harrington RM, Henley MB, Tencer AF. Biomechanical effects of internal fixation of the distal tibiofibular syndesmotic joint: comparison of two fixation techniques. J Orthop Trauma 1994;8:215–9. 26. Needleman RL, Skrade DA, Stiehl JB. Effect of the syndesmotic screw on ankle motion. Foot Ankle 1989;10:17–24. 27. Marvan J, Dzupa V, Krbec M, Skala-Rosenbaum J, Bartoska R, Kachlik D, et al. Distal tibiofibular synostosis after surgically resolved ankle fractures: An epidemiological, clinical and morphological evaluation of a patient sample. Injury 2016;47:2570–4. 28. Albers GH, de Kort AF, Middendorf PR, van Dijk CN. Distal tibiofibular synostosis after ankle fracture. A 14-year follow-up study. J Bone Joint Surg Br 1996;78:250–2. 29. Hinds RM, Lazaro LE, Burket JC, Lorich DG. Risk factors for posttraumatic synostosis and outcomes following operative treatment of ankle fractures. Foot Ankle Int 2014;35:141–7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ayak bileği kırıklı çıkıklarında cerrahi tedavisi sonrası zayıf klinik sonuçlara yol açan yaygın komorbiditeler Dr. Mustafa Yalın,1 Dr. Furkan Çağlayan Aslantaş,2 Dr. Altuğ Duramaz,3 Dr. Mustafa Gökhan Bilgili,3 Dr. Emre Baca,3 Dr. Alican Koluman3 1 2 3

Elazığ Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, Elazığ Ardahan Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Ardahan Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul

AMAÇ: Ayak bileği kırıklı çıkığı kemik ve ayak bileğini çevreleyen yumuşak doku için büyük travmatik bir olaydır. Kemik stabilizasyonu, eklem immobilizasyonu, anatomik redüksiyon ve yumuşak doku koruması için müdahale mümkün olduğunca erken yapılmalıdır. Bu çalışmanın amacı, ayak bileği kırıklı çıkığı olan hastalarda ameliyat sonrası görülebilen majör komorbiditelerin sıklığını ve travma mekanizması ile bu komorbiditelerin klinik durumu arasındaki ilişkiyi belirlemektir. GEREÇ VE YÖNTEM: Mayıs 2014–Şubat 2017 tarihleri arasında ayak bileği kırıklı çıkığı olan 30 hasta (25 erkek, 13 kadın) geriye dönük olarak incelendi. Tüm hastalar ameliyat sonrası en az 24 ay klinik ve radyolojik olarak değerlendirildi. Tüm hastalarda artroz, sinostoz, kondral lezyon varlığı araştırıldı ve AOFAS skorları ile fonksiyonel sonuçlar incelendi. BULGULAR: Açık ayak bileği kırıklı çıkıklarında ortalama AOFAS skoru kapalı kırıklı çıkıklardan daha düşüktü (p=0.044). Eşlik eden bir osteokondral lezyonun (OCL) ve artmış hasta yaşının artroz gelişimi ile güçlü bir şekilde ilişkili olduğu bulundu (sırasıyla, p=0.005 ve p=0.017). Primer cerrahi uygulanan 29 hastanın dördü ve basamaklı cerrahi uygulanan dokuz hastanın dördünde AOFAS skorları kötü saptandı (p=0.071). Çıkık yönü ile AOFAS skorları arasında anlamlı ilişki bulunmadı (p=0.087). TARTIŞMA: Açık ayak bileği kırıklı çıkığı olan hastalarda klinik ve fonksiyonel sonuçların daha kötü olduğu, artroz oranının yaşla arttığı ve sindezmosis vida kullanımının klinik ve fonksiyonel sonuçlar üzerinde istatistiksel olarak anlamlı bir etkiye sahip olmadığı gözlenmiştir. Anahtar sözcükler: Ayak bileği artrozu; ayak bileği kırıklı çıkığı; ayak bileği osteokondral lezyonu; sindesmoz fiksasyonu. Ulus Travma Acil Cerrahi Derg 2020;26(6):943-950

950

doi: 10.14744/tjtes.2020.35392

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

CA S E R EP O RT

Pancreatic cystic echinococcosis causing acute pancreatitis Sabahattin Destek, M.D.,1

Kamuran Cumhur Değer, M.D.2

Department of General Surgery, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, İstanbul-Turkey

Department of General Surgery, Bezmialem Vakıf University Faculty of Medicine, İstanbul-Turkey

ABSTRACT Echinococcosis is a zoonotic infestation, most commonly arises from Echinococcus granulosus helminth. The definitive hosts are carnivora, such as dogs and cats, and the intermediate hosts are herbivores, including cattle, sheep and goats. Humans are intermediate hosts, causing cystic echinococcosis. In our country, the incidence of echinococcos is 14%. The disease is localized in the liver by 70%. Cyst hydatid localized in the pancreas is unusual, with an incidence of 0.2–0.6%, and rarely causes acute pancreatitis. In this report, we present a 45-year-old male patient with cyst hydatid, which manifested by an acute pancreatitis attack. In the examination, there was a CE2 type according to WHO classification stage III cyst hydatid of 97 mm diameter with septa associated with Wirsung duct, acute pancreatitis and splenomegaly. The indirect hemagglutination test was >1: 2560. The patient underwent pancreatectomy and splenectomy following medical therapy with Albendazole tablet for four weeks. IHA of the patient was found as 1/32 in the third month. Cyst hydatid should be considered in the differential diagnosis of all cystic masses, especially in the regions where the disease is endemic. In addition, it should be remembered that although rarely seen, pancreatic cyst hydatid may cause acute pancreatitis. Keywords: Acute pancreatitis; Echinococcus granulosus; pancreatic cystic echinococcosis.

INTRODUCTION Echinococcus, a tropical disease, affects more than 1 million people worldwide.[1] The definitive hosts for adult Echinococcus cestodes are carnivore, such as dogs, foxes, and cats, while the intermediate hosts for larva metacestodes are herbivores, including sheep, goats, and cattle.[1,2] Humans are incidental intermediate hosts.[1,2] Echinococcosis is localized in the liver by 70% and lungs by 20%.[2,3] Causative agent of echinococcus is E. granulosus by 90%.[4] The disease is endemic in South America, the Middle East, Central Asia, East Africa and Australia.[3,4] Its incidence is 50/100.000 per year and prevalence is 5% to 10%.[4,5] In our country, the incidence has been reported as 6.3/100.000 annually, and the prevalence as 14%.[5] Pancreatic cystic echinococcosis (PCE) is an unusual localization of involvement with a prevalence of 0.2–0.6%.[6,7] PCE may cause recurrent acute pancreatitis by compression or

fistulization to the pancreatic duct and obstructive jaundice. In this report, we presented a 45-year-old male patient who was examined due to an acute pancreatitis attack and treated with the diagnosis of PCE. The patient’s consent was obtained for the case report.

[8–10]

CASE REPORT Physical examination of a 45-year-old male patient who presented with the complaints of abdominal pain, nausea, vomiting and fever, revealed tenderness in the epigastric area, abdominal distension, 38.7°C fever, and a palpable abdominal mass in the left upper quadrant. The body mass index of the patient was 29.8 kg/m2. In the blood tests, there were increases in leukocyte (17.500 uL), C reactive protein (CRP) (57 mg/L), liver function tests (AST 273 U/L ALT 312 U/L, LDH 440 U/L, GGT 120 U/L), amylase (2143 U/L) and lipase (586 U/L).

Cite this article as: Destek S, Değer KC. Pancreatic cystic Echinococcosis causing acute pancreatitis. Ulus Travma Acil Cerrahi Derg 2020;26:951-954. Address for correspondence: Sabahattin Destek, M.D. Sancaktepe Şehit Prof. Dr. İlhan Varank Egitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, 34785 İstanbul, Turkey Tel: +90 216 - 606 33 00 E-mail: sebahattindestek@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(6):951-954 DOI: 10.14744/tjtes.2019.85069 Submitted: 25.05.2019 Accepted: 11.11.2019 Online: 27.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

951

Destek et al. Pancreatic cystic Echinococcosis causing acute pancreatitis

On the tomography ordered, a cyst hydatid of 97x85x74 mm in the corpus-tail section of the pancreas, acute edematous interstitial pancreatitis and splenomegaly were found. PCE and duct of Wirsung seemed associated. Varicose venous structures were found in the splenic hilus and omentum due to the splenic vein compression by PCE. On magnetic resonance imaging (MRI), PCE was seen to be associated with the duct of Wirsung. PCE was compatible with World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) CE2 type according to the radiological features. Echinococcosis was not found in the regions out of the pancreas (Fig. 1). Indirect hemagglutination test (IHA) result was high (>1:2831) (ref: <1:160). The patient was hospitalized and administered early enteral feeding, pain therapy and fluid replacement, and albendazole was initiated as 15 mg/kg/ day with the diagnosis of Ranson III acute pancreatitis and PCE. He was discharged after one week. Albendazole was continued for one month. In the control tests, leukocyte,

CRP, amylase, lipase and liver function tests were returned to normal. IHA was found as >1:1847. The patient was decided to undergo surgery. In the laparoscopic exploration, left-sided (sinistral) portal hypertension findings due to PCE compression, such as distinct varicose veins in the splenic vein, gastrica breves and omentum, were detected. Since the PCE was large and very adherent to the surrounding tissues, open surgery was performed. Distal pancreatectomy and splenectomy were performed in the patient to involve PCE. Germinative membrane and hydatid sand structures were detected in the duct of Wirsung during resection of the pancreas. The duct of Wirsung was washed and cleaned with a physiological saline solution. The duct of Wirsung was sutured. The piece was taken out of the abdomen (Fig. 2). The patient was discharged on the postoperative 8th day. In the histopathological examination, echinococcosis was 10x7

(a)

(b)

Figure 1. Pancreatic echinococcosis. (a) Computed tomography image showing an Echinococcus granulosus cyst containing daughter cysts within the pancreas. (b) Coronal T2 magnetic resonance cholangiopancreatography of the cyst - pancreatic fistula, Axial T1 and T2 magnetic resonance image showing an Echinococcus granulosus cyst containing daughter cysts within the pancreas.

Figure 2. Pancreatic cystic echinococcosis in the operation.

952

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Destek et al. Pancreatic cystic Echinococcosis causing acute pancreatitis

cm in size, and numerous scolex and germinative membrane were detected. Albendazole at a dose of 15 mg/kg/day was continued for postoperative three months. No problem was detected on the control tomography performed in the postoperative 3rd month. IHA of the patient was negative in the 3rd month. Patient consent was obtained for this study.

DISCUSSION Echinococcosis is frequently seen in the regions where agriculture and stock raising are widespread.[11] Pathogenic CE species in humans are E. granulosus sensu stricto (G1-G3), E. equinus (G4), E. ortleppi (G5) and E. canadensis (G6-G10). The causative agent in CE is E. granulosussensu stricto G1genotype by 88%.[1,2,4] These agents cause cystic echinococcosis (CE) consisting of protoscoleces and daughter vesicles.[2] Ten percent of CE may develop in an unusual localization, such as the spleen (6%), kidneys (2%), and brain (2%).[1,12] The incidence of PCE is lower than 2%.[10,11] The embryos reach the pancreas most commonly through the hematogenous spread, local spread from the biliary system, lymphatic passage from the intestinal mucosa and retroperitoneal spread.[7,11] PCE is usually seen in men and in the 3rd-4th decades of life.[9,11] PCE may occur as primary (isolated pancreas) or secondary (multiple organs).[10,11] Of all the PCE cases, 28% are primary.[11] In published studies, 90% of PCEs are solitary, with 50% are found in the head, 34% in the corpus, and 16% in the tail of the pancreas.[11–13] The diameter of PCE may vary between 26 and 180 mm.[11] Our case was a 45-year-old male patient with a primary, solitary PCE in the body-corpus section of the pancreas with a diameter of 97 mm. The clinical picture depends on the localization of PCE in the pancreas.[9–11] The main symptoms include pain in the epigastric region (69%) or left upper quadrant (31%), jaundice (26%), nausea-vomiting (16%) and fever (8%).[7,11] The main complications are pancreatitis (15%), sinistral portal hypertension (12.5%), cholangitis, duodenal stenosis and duodenal fistula.[8,11,13] In our patient, the most significant complaint was upper abdominal pain, while pancreatitis and sinistral portal hypertension were found together with PCE. When receiving medical history, living in endemic regions should be considered.[11] Ultrasonography is a noninvasive and low-cost method; however, its sensitivity is low since the pancreas is localized retroperitoneally.[6,11] Tomography is successful in the determination of the size and localization of PCE, its association with the pancreato-biliary system, and detection of postoperative recurrence.[10,11] MRI is useful in the identification of the fistulas between PCE and pancreas and biliary ducts. Endoscopic ultrasonography can be performed to determine the fistulas between PCE and pancreas and biliary ducts, and to perform a biopsy.[11,14] Endoscopic retrograde cholangiopancreatography can be performed to apply stenting in biliopancreatic obstruction and fistulas.[10,12] Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Radiologically, WHO-IWGE classifications are used in the grading of CE.[6,14] In our study, PCE was compatible with CE2 type according to WHO-IWGE classification. Several tests, such as enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination, serum immunoelectrophoresis, complement fixation and immunofluorescence assays, are used for diagnosis, screening and follow up.[2,12] The seropositivity rate in PCE is approximately 54%.[11,10] On the other hand, seronegativity does not rule out echinococcosis. [1,2] In our patient, the IHA test was positive. Differential diagnosis of PCE includes pancreas cystadenoma, cystadenocarcinoma, cystic metastatic lesions, congenital pancreas cysts and pseudocysts.[7,11] Fine needle aspiration biopsy or cyst fluid aspiration cytology with percutaneous or endoscopic ultrasonography can be performed in patients in whom diagnosis cannot be established.[6,7] In our patient, a biopsy was not needed. Patients’ age, comorbidity, localization and size of the cyst, and its association with the pancreatobiliary system are considered in the selection of a treatment option for PCE.[6,8] Minimal invasive approaches, such as medical therapy, percutaneous catheterization or PAIR (Puncture-aspiration-injection-respiration), and open or laparoscopic surgical methods, are used alone or in combination.[8,12] Partial cystectomy, pericystectomy, distal pancreatectomy and pancreaticoduodenectomy may be performed.[6,8,15] Splenectomy may also be added in the case of splenic vein invasion or occlusion.[9,13] To reduce the risk of anaphylaxis and recurrence, prophylactic treatment (albendazole, mebendazole, praziquentel) should be administered in the pre- and postoperative periods before and after surgery for three to four weeks.[12,15] Postoperative early complications include pancreatic fistulas, biliary fistulas, biloma, intraabdominal abscess and wound infection.[8,11] The late complication is a recurrence of echinococcosis.[6,7] We also administered prophylactic medical therapy in our patient. The patient who underwent distal pancreatectomy and splenectomy did not develop postoperative complications. In conclusion, PCE is a rare parasitic infestation, which may cause serious pancreatobiliary complications. It should be remembered in the differential diagnosis of pancreatic cysts in endemic areas. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study 953

Destek et al. Pancreatic cystic Echinococcosis causing acute pancreatitis

has received no financial support.

REFERENCES 1. Agudelo Higuita NI, Brunetti E, McCloskey C. Cystic Echinococcosis. J Clin Microbiol 2016;54:518–23. 2. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis 2009;13:125–33. 3. Alvarez Rojas CA, Romig T, Lightowlers MW. Echinococcus granulosus sensu lato genotypes infecting humans--review of current knowledge. Int J Parasitol 2014;44:9–18. 4. Yazar S, Ozkan AT, Hökelek M, Polat E, Yilmaz H, Ozbilge H, et al. Cystic echinococcosis in Turkey from 2001-2005. [Article in Turkish]. Turkiye Parazitol Derg 2008;32:208–20. 5. Sayır F, Çobanoğlu U. A parasitic disease which is endemic in our region: Hydatid cyst. Van Med J 2013;20:288–93. 6. Dziri C, Dougaz W, Bouasker I. Surgery of the pancreatic cystic echinococcosis: systematic review. Transl Gastroenterol Hepatol 2017;2:105. 7. Bayat AM, Azhough R, Hashemzadeh S, Barband A, Yaghoubi AR, Gargari RM. Hydatid cyst of pancreas presented as a pancreatic pseudocyst. Am J Gastroenterol 2009;104:1324–6. 8. Alsaid B, Alhimyar M, Rayya F. Pancreatic Hydatid Cyst Causing Acute

Pancreatitis: A Case Report and Literature Review. Case Rep Surg 2018;2018:9821403. 9. Ozsay O, Gungor F, Karaisli S, Kokulu I, Dilek ON. Hydatid cyst of the pancreas causing both acute pancreatitis and splenic vein thrombosis. Ann R Coll Surg Engl 2018;100:e178–80. 10. Akbulut S, Yavuz R, Sogutcu N, Kaya B, Hatipoglu S, Senol A, et al. Hydatid cyst of the pancreas: Report of an undiagnosed case of pancreatic hydatid cyst and brief literature review. World J Gastrointest Surg 2014;6:190–200. 11. Ahmed Z, Chhabra S, Massey A, Vij V, Yadav R, Bugalia R, et al. Primary hydatid cyst of pancreas: Case report and review of literature. Int J Surg Case Rep 2016;27:74–7. 12. Dziri C, Haouet K, Fingerhut A. Treatment of hydatid cyst of the liver: where is the evidence?. World J Surg 2004;28:731–6. 13. Canbak T, Acar A, Kıvanç AE, Başak F, Kulalı F, Baş G. Sinistral Portal Hypertension Due to Pancreatic Hydatid Cyst. Türkiye Parazitol Derg 2017;41:226–8. 14. Stojkovic M, Rosenberger K, Kauczor HU, Junghanss T, Hosch W. Diagnosing and staging of cystic echinococcosis: how do CT and MRI perform in comparison to ultrasound?. PLoS Negl Trop Dis 2012;6:e1880. 15. Trigui A, Rejab H, Guirat A, Mizouni A, Ben Amar M, Mzali R, et al. Hydatid cyst of the pancreas. About 12 cases. Ann Ital Chir 2013;84:165–70.

OLGU SUNUMU - ÖZET

Akut pankreatite neden olan pankreas kistik ekinokokkozisi Dr. Sabahattin Destek,1 Dr. Kamuran Cumhur Değer2 1 2

Sancaktepe Sehit Prof. Dr. İlhan Varank Egitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Bezmialem Vakıf Universitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

Ekinokokkosiz, genellikle Echinococcus granulosus helmintinin neden olduğu zoonotik bir enfestasyondur. Köpek ve kedi gibi etoburlar kesin konakçı iken sığır, koyun keçi gibi otoburlar ara konakçıdırlar. İnsanlar ara konakçı olup onlarda kistik ekinokokkosize neden olurlar. Ülkemizde insidansı %14’dür. Hastalık %70 oranında karaciğerde yerleşir. Kist hidatiğin pankreasa yerleşmesi sıra dışı olup %0.2–0.6 oranında rastlanır ve nadiren akut pankreatite neden olur. Bu sunumda, akut pankreatit atağı ile kendini gösteren pankreas kist hidatiği saptanılan 45 yaşında bir erkek olgu sunuldu. İncelemelerinde pankreas gövde-kuyruk bölgesinde 97 mm çapında wirsung kanalı ile iştirakli, WHO sınıflandırmasına göre CE2 tipinde evre III kist hidatik, akut pankreatit ve splenomegali saptandı. İndirekt hemaglütinasyon testi >1: 2560 idi. Albendazol tablet ile dört hafta tıbbi tedavi sonrasında hastaya distal pankreatektomi ve splenektomi yapıldı. Hastanın üçüncü ayında IHA sonucu 1/32 olarak bulundu. Özellikle hastalığın endemik olduğu coğrafi bölgelerde, pankreastaki tüm kistik kitlelerin ayırıcı tanısında kist hidatik göz önünde bulundurulmalıdır. Ayrıca pankeas kist hidatiğinin nadir görülmesine rağmen akut pankreatite neden olabileceği akla getirilmelidir. Anahtar sözcükler: Akut pankreatit; Echinococcus granulosus; pankreas kistik ekinokokkozisi. Ulus Travma Acil Cerrahi Derg 2020;26(6):951-954

954

doi: 10.14744/tjtes.2019.85069

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

CA S E R EP O RT

Free perforation of primary small bowel lymphoma in a patient with celiac sprue and dermatitis herpetiformis Hacı Bolat, M.D.,1

Zafer Teke, M.D.2

Department of General Surgery, Niğde Ömer Halisdemir University Faculty of Medicine, Niğde-Turkey

Department of Surgical Oncology, Çukurova University Faculty of Medicine, Adana-Turkey

ABSTRACT Small bowel lymphomas are rare and constitute approximately 1% of the malignant gastrointestinal tumors. However, the risk of malignant disease in adult celiac disease is about 8–10%, and non-Hodgkin lymphoma is the most common. In the literature, cases with celiac disease and small bowel lymphoma have been reported, but the emphasis on emergency surgery is extremely rare. We herein present a case of primary small intestinal lymphoma diagnosed after surgery in a 55-year-old male patient who presented to our emergency department with findings of gastrointestinal perforation and had a history of celiac disease and dermatitis herpetiformis. The purpose of this report is to review this situation briefly and discuss it in the light of literature. Keywords: Celiac disease; dermatitis herpetiformis; free perforation; gluten; intestinal lymphoma; non-Hodgkin lymphoma; small bowel lymphoma; small bowel perforation.

INTRODUCTION Small bowel malignancies are very rare. The small intestine has three-quarters of the length of the digestive tract, but small bowel malignancies account for approximately 1–5% of gastrointestinal cancers. Lymphomas encompass 15% of small bowel malignancies[1] and are most commonly seen in the ileum. Among the risk factors related to the development of small bowel lymphomas, there exists celiac disease, as well as dermatitis herpetiformis. Celiac disease is an autoimmune disease characterized by gluten intolerance and damage to small intestinal villi.[2] The risk of small bowel tumors increases in celiac disease. Lymphoma develops most frequently; however, adenocarcinoma may rarely develop.[3] Dermatitis herpetiformis is a chronic, polymorphic and itchy skin disease that often develops in patients with latent gluten-sensitive enteropathy.[4] The interesting connection between celiac disease and dermatitis herpetiformis has been revealed by understanding that lymphoma

may be the first clinical manifestation of the celiac disease or aggravate dermatitis herpetiformis.[5–8] We herein present a case of primary small intestinal lymphoma diagnosed after surgery in a 55-year-old male patient who presented to our emergency department with free perforation findings and had a history of celiac disease and dermatitis herpetiformis. The purpose of this report is to review this situation briefly and discuss it in the light of literature.

CASE REPORT A 55-year-old male was admitted to our emergency service with complaints of abdominal pain, nausea and vomiting, and absence of gas-feces discharge for one day. He had a 35-year history of celiac sprue and dermatitis herpetiformis with compliance to a gluten-free diet strictly. His medical history also included arterial hypertension. On physical examination, the abdomen was distended, and there exist defense musculaire and rebound tenderness upon palpation of the abdomen.

Cite this article as: Bolat H, Teke Z. Free perforation of primary small bowel lymphoma in a patient with celiac sprue and dermatitis herpetiformis. Ulus Travma Acil Cerrahi Derg 2020;26:955-959. Address for correspondence: Hacı Bolat, M.D. Niğde Ömer Halisdemir Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Niğde, Turkey Tel: +90 388 - 225 60 50 E-mail: hbolat01@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(6):955-959 DOI: 10.14744/tjtes.2019.49067 Submitted: 20.07.2019 Accepted: 17.11.2019 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

955

Bolat et al. Free perforation of primary small bowel lymphoma in a patient with celiac sprue and dermatitis herpetiformis

The bowel sounds were hypoactive. Digital rectal examination revealed an empty rectum. White blood cell count was 11.2 103/ÎźL. A computed tomography (CT) of the abdomen showed that there was a wall thickening of 15 mm measured at the thickest part consistent with diffuse mucosal edema in the jejunal loops of the small intestine. At the umbilical level, free air densities were observed on the anterior abdominal wall (Fig. 1). At the laparotomy, there was a perforation area of 0.5 cm in the antimesenteric side of the jejunum 50

Figure 1. An axial CT section showing a wall thickening of 15 mm measured at the thickest part consistent with diffuse mucosal edema in the jejunal loops of the small intestine, and free air densities at the umbilical level on the anterior abdominal wall.

(a)

cm distal to the ligament of Treitz (Fig. 2a). Jejunal loops of approximately 50 cm, including this perforation area, were edematous and inflamed. These small bowel loops were resected and an end-to-end anastomosis was performed. In the pathological examination, macroscopically, 6x2.5x2 cm ulcerated lesion with irregular borders and incised face similar to fish meat was observed in the area corresponding to the perforated region (Fig. 2b). There was no tumor at the surgical margins. Histopathological microscopic examination showed that the small bowel mucosa was completely ulcerated in the defined area. In this area, tumor formation consisting of atypical lymphoid cells with hyperchromatic nuclei, a few nucleoli and narrow basophilic cytoplasm was remarkable throughout the wall (Fig. 3a). This tumor infiltrated the entire wall but did not reach the serosa. Many atypical mitosis, lymphovascular invasion, and desmoplastic reactions were observed. It was morphologically compatible with non-Hodgkin lymphoma (NHL). Immunohistochemical examinations revealed CD10, CD19, CD20 and bcl6 negativity. However, CD3 (Fig. 3b), CD4 (Fig. 3c) and CD43 expressions were positive, and focally positive immunoreactivity to CD5 was determined. These findings were reported as T-cell NHL. The patient was discharged seven days after the surgery without any problem. After the surgery, chemotherapy was planned to be added to the treatment, and he was referred

(b)

Figure 2. (a) A perforation area of 0.5 cm in the antimesenteric side of the jejunum 50 cm distal to the ligament of Treitz. (b) Macroscopically, 6x2.5x2 cm ulcerated lesion with irregular borders and incised face similar to fish meat in the area corresponding to the perforated region.

(a)

(b)

(c)

Figure 3. (a) Tumor formation consisting of atypical lymphoid cells with hyperchromatic nuclei, a few nucleoli and narrow basophilic cytoplasm throughout the wall (H&E, x 200). (b) Malignant lymphocytes showing positive immunohistochemical staining for CD3 (x100). (c) Malignant lymphocytes showing positive immunohistochemical staining for CD4 (x200).

956

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Bolat et al. Free perforation of primary small bowel lymphoma in a patient with celiac sprue and dermatitis herpetiformis

to the department of medical oncology. However, the patient died of a heart attack on the 45th postoperative day. The patient’s consent was obtained for this study.

DISCUSSION Lymphomas are simply the malignant transformation of normal lymphoid cells in lymphoid tissues. This condition occurs predominantly in the lymph nodes (nodal lymphoma), but more rarely may occur in organs containing lymphoid tissue (extra-nodal lymphoma). Of these extra-nodal areas, the gastrointestinal tract (GIT) is an important area. GIT involvement during the natural course of lymphomas occurs in two different ways. The cases where malignant transformation predominantly and primarily arises from GIT are called primary gastrointestinal lymphomas and their treatment is directed to the localized area. In a patient who has been previously diagnosed with nodal lymphoma, GIT may be involved and they can be defined as secondary gastrointestinal lymphomas. Whether GIT involvement is primary or secondary, GIT involvement is predominantly in the form of NHL, and Hodgkin’s disease is very rare. Gastrointestinal lymphomas develop from T or B cells. They encompass Burkitt lymphomas, mantle cell lymphomas, diffuse large B cell lymphomas, and mucosa-associated lymphoid tissue (MALT) lymphomas. In the presented case, the T-cell NHL was detected. Primary NHLs occupy approximately 1–4% of all GIT neoplasms, while GIT involvement in secondary NHLs may reach up to 10% in the early stages of the disease and 60% in terminal periods. In summary, GIT is an important system that is affected during lymphomas. Forty percent of lymphomas can be grouped as indolent (survival is expressed in years), 55% as aggressive (survival is expressed in months) and 5% as very aggressive (survival is expressed in weeks). When the distribution within GIT was examined, the stomach was the first with 75%, followed by involvement of the small bowel (9%), ileocecal region (7%), rectum (2%), colon (1%) and multiple bowel regions (6%).[9] The most common sites of small bowel lymphomas are the ileum (60–65%), jejunum (20–25%) and duodenum (6–8%), respectively. They usually settle in multiple foci, and 15% of cases have skip lesions.[10] Lymphoma, which aggravates celiac disease, is frequently seen in the jejunum.[11,12] In our patient, the lymphoma involved the jejunum. Celiac disease is an autoimmune disease associated with gluten and shows genetic transmission.[13,14] Celiac disease is seen with a frequency of 0.5–1% in various countries of the world[14] and is more common in women, but the association with small bowel tumor is more common in men.[3] Our case was a 55-year-old man with small bowel lymphoma concerning celiac disease, as reported in the literature. The risk of small bowel tumor increases approximately 60–80 times in celiac disease.[15] Small bowel lymphoma is approximately 10 times more common than adenocarcinoma.[16] The number of cases with celiac disease and small bowel NHL is relativeUlus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

ly low in the literature.[3] Additionally, intestinal lymphoma may aggravate dermatitis herpetiformis.[17,18] In our patient, celiac disease was diagnosed 35 years before presenting with an acute abdomen due to a perforating lymphoma while on a gluten-free diet. In the same way, the diagnosis of dermatitis herpetiformis was established in this patient with small bowel lymphoma before the clinical picture of an acute abdomen. The symptomatology of celiac disease varies, and patients may present with various symptoms. Gastrointestinal symptoms include diarrhea and abdominal pain, whereas extra-gastrointestinal ones are chronic anemia, increased liver function tests, arthritis, osteoporosis, skin disorders, and neurologic abnormalities. Sometimes, patients with celiac disease may be asymptomatic for a long time and may present with findings related only to small bowel mass before the diagnosis of celiac disease.[3] In the patient reported here, dermatitis herpetiformis, which is an accompanying clinical entity of celiac disease, was evident. Small bowel malignancies usually manifest themselves with gastrointestinal discomforts. Among the most common presenting symptoms are abdominal pain (75%), losing weight (28%), intestinal obstruction (25%), and hemorrhage (24%). Diagnosis is mostly delayed if the clinical presentation at the time of admission does not include a condition requiring urgent intervention, such as obstruction, hemorrhage or free perforation. Ten percent of patients with small intestine malignancies have bowel perforation at the time of admission to the emergency department. Intestinal perforation mostly arises from lymphoma or sarcoma. Our patient had a small bowel perforation as the first clinical presentation of his NHL. He admitted to the emergency room with an acute abdomen requiring surgical intervention. The patient had exploratory laparotomy and we did not clinically suspect small bowel lymphoma before surgery. The diagnostic workup begins with a detailed history of the patient and a physical examination. Laboratory analysis should include complete blood count, serum electrolytes, and liver function tests. Since the risk of tumor development is high in celiac disease, the use of noninvasive imaging methods, such as CT and MRI, as well as endoscopic examinations, is important in early diagnosis. CT scan has a sensitivity of 80% for the detection of small intestinal lesions and if CT or MR enterography is carried out, this rate increases to 85% to 95%. [19,20] Our patient’s preoperative CT scan showed a wall thickening with diffuse mucosal edema in the jejunal loops and free air densities at the umbilical level. In our case, there was an abdominal pain localized around the umbilicus, which started abruptly one day ago, and preoperative radiographic imaging methods indicating perforation of a hollow viscus with intraabdominal free air were applied. MRI has an important role in the differential diagnosis of benign and malignant lesions and in the characterization of the mass. Concomitant diffusion-weighted imaging increases the efficiency of accurate diagnosis. Endoscopy is a very useful diagnostic tool for the detection of proximal small intestinal malignancies, such as 957

Bolat et al. Free perforation of primary small bowel lymphoma in a patient with celiac sprue and dermatitis herpetiformis

those in the duodenum and for obtaining biopsies from these lesions. Double balloon enteroscopy is a method used to detect small bowel malignancies located beyond the ligament of Treitz. Video capsule endoscopy is a noninvasive method that is increasingly used in advanced referral centers for visualization of the small intestine. In patients with signs of upper or lower digestive system bleeding or bowel obstruction, if there is no diagnosis yet, but if there is a high degree of clinical suspicion, then exploratory celiotomy should be performed and surgeon-assisted intraoperative endoscopy can provide visualization of all segments of the small bowel to the finest detail. Diagnostic laparoscopy is also a useful method for visualization of the peritoneal cavity and for obtaining multiple biopsies, even without gastrointestinal complications. Celiac disease progresses with atrophy and fissures, and these pathological changes are more commonly seen in intestinal villi secondary to autoimmune changes and chronic inflammation, and rarely, polyp development, ulceration, benign stenosis secondary to chronic inflammation, and malignant masses can be seen.[21] On the other hand, small bowel lymphomas can be seen as a polypoid, infiltrative or exophytic mass. Accompanying mesenteric lymphadenopathy is more common in lymphoma. In our case, there was no lesion causing luminal narrowing and obstruction, but diffuse mucosal edema and wall thickening were observed in the jejunal loops. Macroscopically, 6x2.5x2 cm ulcerated lesion with irregular borders and an incised face reminiscent of fish meat was observed in the perforated region. Besides, in this patient who developed free perforation, there was no granuloma or vasculitis, which is one of the pathognomonic signs of Crohn’s disease.[22] Studies have shown that small bowel malignancies may occur in celiac disease.[11,12,15] Most of these small intestinal malignancies consist of lymphomas, but there has also been an increase in the incidence of small intestinal carcinoma.[23] Small bowel lymphomas may invade the mucosa, causing ulceration and sometimes bleeding or perforation, whereas expansive growth may result in obstruction of the intestine. The development of an ulcer in the mucosa of the small intestine is a concern for the development of a possible lymphoma in celiac disease. However, perforation due to malignant ulcers in the digestive tract is extremely rare in celiac disease. The estimated free perforation development rate is approximately 1–2%. [24] This rate is similar to the incidence of free perforation of the small intestine of 1.5% in Crohn’s disease.[22] Any region within the digestive system is a potential candidate for this free perforation complication in celiac disease. This ominous complication may emerge unexpectedly, even in stable celiac disease, after visibly adapting to a gluten-free diet for many years. This case report describes a patient with stable celiac disease and dermatitis herpetiformis. The first clinical manifestation of lymphoma in celiac disease was a free perforation in the small intestine. Lymphoma occurred despite our patient surviving on a gluten-free diet. Free perforation developed unexpectedly, mostly as the first clinical presentation of the lymphoma in celiac disease. Small bowel perforation in celiac disease is 958

an inauspicious clinical manifestation frequently regarded as an ominous forerunner of lymphoma in celiac disease. The centrepiece of management for celiac disease is a gluten-free diet, which involves evasion of the gluten-containing cereals wheat, rye, and barley. Allowed cereals encompass rice, oats, buckwheat, corn, millet, and quinoa. A patient diagnosed with celiac disease will benefit from a consultation with a dietician who can assist in appropriate food selection and prevention. The basis of the treatment of dermatitis herpetiformis is a strict gluten-free diet that is healthy, which may prevent the development of lymphoma and other diseases related to gluten-induced enteropathy and malabsorption.[25–27] Strict adherence to a gluten-free diet is critical for clinical improvement of the disease and histological healing of the small intestine. However, the definite effects of certain dietary treatments on the prevention of different complications of the celiac disease still deserve further investigation. Strict adherence to a gluten-free diet may not provide complete protection against the risk of lymphoma in celiac disease. Patients with no complications due to small bowel lymphoma should be treated with chemotherapy, similar to patients with systemic lymphoma.[28] However, systemic chemotherapy is contraindicated in patients with small bowel lymphoma where severe complications, such as hemorrhage, obstruction and perforation develop and require immediate medical or surgical intervention if the patient’s general condition and concomitant systemic diseases permit an operation. During laparotomy, a tumor-containing segment of the small intestine is resected, and other small bowel loops should be carefully examined to avoid overlooking potential skip lesions if any. Unlike other primary small intestinal cancers, extensive mesenteric excision is not required. The remaining lymph nodes are managed with systemic chemotherapy after the patient is discharged. In our patient, emergent exploratory laparotomy revealed a 0.5-cm perforation over the jejunum. Partial small bowel resection with end-to-end anastomosis was done. Chemoradiation may be preferred in patients who cannot withstand cytotoxic systemic chemotherapy. However, the complication rates of radiation therapy are high for tumor necrosis, hemorrhage and intestinal perforation.

Conclusion In conclusion, considering the difficulties in the diagnosis of small bowel tumors, it should be kept in mind that a small bowel perforation that we encountered during surgery may belong to a small bowel lymphoma and complications that may arise from this tumor should be well known. Small intestine malignancies are rarely seen as a cause of free perforation and can be delayed in diagnosis. The diagnostic value of imaging modalities is limited in patients with small intestinal lymphoma. In such cases, surgical intervention may always be necessary for both diagnosis and treatment. In our patient, the diagnosis of small bowel lymphoma was made by exploratory laparotomy only after free perforation developed. Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Bolat et al. Free perforation of primary small bowel lymphoma in a patient with celiac sprue and dermatitis herpetiformis

Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: H.B., Z.T.; Design: H.B., Z.T.; Supervision: H.B., Z.T.; Resource: H.B., Z.T.; Materials: H.B., Z.T.; Data: H.B., Z.T.; Analysis: H.B., Z.T.; Literature search: H.B., Z.T.; Writing: H.B., Z.T.; Critical revision: H.B., Z.T. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Bilimoria KY, Bentrem DJ, Wayne JD, Ko CY, Bennett CL, Talamonti MS. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg 2009;249:63–71. 2. Spijkerman M, Tan IL, Kolkman JJ, Withoff S, Wijmenga C, Visschedijk MC, et al. A large variety of clinical features and concomitant disorders in celiac disease - A cohort study in the Netherlands. Dig Liver Dis 2016;48:499–505. 3. Rampertab SD, Forde KA, Green PH. Small bowel neoplasia in coeliac disease. Gut 2003;52:1211–4. 4. Kárpáti S. Dermatitis herpetiformis. Clin Dermatol 2012;30:56–9. 5. Brow JR, Parker F, Weinstein WM, Rubin CE. The small intestinal mucosa in dermatitis herpetiformis. I. Severity and distribution of the small intestinal lesion and associated malabsorption. Gastroenterology 1971;60:355–61. 6. Weinstein WM, Brow JR, Parker F, Rubin CE. The small intestinal mucosa in dermatitis herpetiformis. II. Relationship of the small intestinal lesion to gluten. Gastroenterology 1971;60:362–9. 7. Weinstein WM. Latent celiac sprue. Gastroenterology 1974;66:489–93. 8. Freeman HJ, Weinstein WM, Shnitka TK, Piercey JR, Wensel RH. Primary abdominal lymphoma. Presenting manifestation of celiac sprue or complicating dermatitis herpetiformis. Am J Med 1977;63:585–94. 9. Dawson IM, Cornes JS, Morson BC. Primary malignant lymphoid tumours of the intestinal tract. Report of 37 cases with a study of factors influencing prognosis. Br J Surg 1961;49:80–9. 10. Nakamura S, Matsumoto T, Iida M, Yao T, Tsuneyoshi M. Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends. Cancer 2003;97:2462–73. 11. Harris OD, Cooke WT, Thompson H, Waterhouse JA. Malignan-

cy in adult coeliac disease and idiopathic steatorrhoea. Am J Med 1967;42:899–912. 12. Cooper BT, Holmes GKT, Ferguson R, Cooke WT. Celiac disease and malignancy. Medicine (Baltimore) 1980;59:249–61. 13. Freeman HJ. Malignancy in adult celiac disease. World J Gastroenterol 2009;15:1581–3. 14. Gujral N, Freeman HJ, Thomson AB. Celiac disease: prevalence, diagnosis, pathogenesis and treatment. World J Gastroenterol 2012;18:6036–59. 15. Askling J, Linet M, Gridley G, Halstensen TS, Ekström K, Ekbom A. Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology 2002;123:1428–35. 16. Green PHR, Stavropoulos SN, Panagi SG, Goldstein SL, Mcmahon DJ, Absan H, et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol 2001;96:126–31. 17. Collin P, Pukkala E, Reunala T. Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease. Gut 1996;38:528–30. 18. Reunala T, Collin P. Diseases associated with dermatitis herpetiformis. Br J Dermatol 1997;136:315–8. 19. Pappalardo G, Gualdi G, Nunziale A, Masselli G, Floriani I, Casciani E. Impact of magnetic resonance in the preoperative staging and the surgical planning for treating small bowel neoplasms. Surg Today 2013;43:613–9. 20. Pilleul F, Penigaud M, Milot L, Saurin JC, Chayvialle JA, Valette PJ. Possible small-bowel neoplasms: contrast-enhanced and water-enhanced multidetector CT enteroclysis. Radiology 2006;241:796–801. 21. Culliford A, Daly J, Diamond B, Rubin M, Green PH. The value of wireless capsule endoscopy in patients with complicated celiac disease. Gastrointest Endosc 2005;62:55–61. 22. Freeman HJ. Spontaneous free perforation of the small intestine in adults. World J Gastroenterol 2014;20:9990–7. 23. Swinson CM, Slavin G, Coles EC, Booth CC. Coeliac disease and malignancy. Lancet 1983;1:111–5. 24. Freeman HJ. Free perforation due to intestinal lymphoma in biopsy-defined or suspected celiac disease. J Clin Gastroenterol 2003;37:299–302. 25. Collin P, Reunala T. Recognition and management of the cutaneous manifestations of celiac disease: a guide for dermatologists. Am J Clin Dermatol 2003;4:13–20. 26. Kárpáti S. Dermatitis herpetiformis: close to unravelling a disease. J Dermatol Sci 2004;34:83–90. 27. Junkins-Hopkins JM. Dermatitis herpetiformis: pearls and pitfalls in diagnosis and management. J Am Acad Dermatol 2010;63:526–8. 28. Patel SH, Fleming JB. Small Bowel Malignancies. In: Feig BW, editor. The MD Anderson Surgical Oncology Handbook. 6th edition. Philadelphia: Wolters Kluwer; 2019. p. 432–51.

OLGU SUNUMU - ÖZET

Çölyak hastalığı ve dermatitis herpetiformisi olan bir hastada primer ince bağırsak lenfomasının serbest perforasyonu Dr. Hacı Bolat,1 Dr. Zafer Teke2 1 2

Niğde Ömer Halisdemir Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Niğde Çukurova Üniversitesi Tıp Fakültesi, Cerrahi Onkoloji Bilim Dalı, Adana

İnce bağırsak lenfomaları oldukça nadir görülmekte olup gastrointestinal malign tümörlerin yaklaşık %1’ini oluşturmaktadır. Ancak, erişkin çölyak hastalığında malign hastalık riski yaklaşık %8–10 arasındadır ve en sık non-Hodgkin lenfoma gelişmektedir. Literatürde çölyak hastalığı ve ince bağırsak lenfomasının birlikte görüldüğü olgular bildirilmekle birlikte acil cerrahi gereksinimi üzerine vurgu son derece nadirdir. Biz bu olgu sunumunda gastrointestinal perforasyon bulguları ile acil servisimize başvuran ve özgeçmişinde çölyak hastalığı ve dermatitis herpetiformis öyküsü bulunan 55 yaşındaki bir erkek hastada operasyon sonrası tanısı konulan primer ince bağırsak lenfomasını sunuyoruz. Bu sunumun amacı, bu klinik durumu kısaca gözden geçirmek ve literatür ışığında tartışmaktır. Anahtar sözcükler: Bağırsak lenfoması; çölyak hastalığı; dermatitis herpetiformis; gluten; ince bağırsak lenfoması; ince bağırsak perforasyonu; Non-Hodgkin lenfoma; serbest perforasyon. Ulus Travma Acil Cerrahi Derg 2020;26(6):955-959

doi: 10.14744/tjtes.2019.49067

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

959

CA S E R EP O RT

Fat embolism syndrome after gluteal augmentation with hyaluronic acid: A case report İlhan Uz, M.D.,

Sercan Yalçınlı, M.D.,

Mehmet Efe, M.D.

Department of Emergency Medicine, Ege University Faculty of Medicine, İzmir-Turkey

ABSTRACT Fat embolism syndrome (FES) occurs classically characterized by the combination of acute respiratory failure, neurologic abnormalities, and a petechial rash. Forty-six-year-old female presented to our emergency department with agitation, altered mental status, and drowsiness.We learned that the patient had received a hyaluronic acid (HA) injection into her buttocks at a beauty center a few hours before her admission. She had no skin findings, but she was hypoxemic. She had lung computed tomography (CT) findings bilateral ground-glass opacities and pleural effusion and had multiple cerebral white lesion on brain magnetic resonance images (MRI). Patients presenting to the emergency department with sudden alteration in mental status should be questioned for recent surgical or invasive aesthetic procedures. Fat embolism syndrome should be considered even if the patient has no petechial rash. Brain MRI and lung CT should be the imaging modality of choice in these patients. Keywords: Emergency medicine; fat embolism syndrome; hyaluronic acid injection.

INTRODUCTION Fat embolism (FE) frequently occurs after trauma and during orthopaedic procedures involving manipulation of intramedullary contents. Fat embolism syndrome (FES) is a very rare clinical diagnosis that is based on the classic triad of hypoxemia (pulmonary distress), neurologic abnormalities, and petechial rash.[1] Although part of the “classic triad” of symptoms, a petechial rash occurs in only 20% to 50% of the patients.[2,3] Hyaluronic acid (HA) is used as a filler material in cosmetics for soft tissue augmentation in various parts of the body. In this case study, we wanted to share a rare case of FES due to after gluteal augmentation with hyaluronic acid for aesthetic.

CASE REPORT Forty-six-year-old female presented to our emergency department with agitation, altered mental status, and drowsiness. We learned that the patient had received a hyaluronic acid (HA) filler injection into her buttocks at a beauty center

a few hours before admission. Her past medical history was unremarkable except for peripheral facial paralysis, and the patient did not use any medication regularly. Her relatives stated that she had received HA injections into her buttocks seven times at the same center previously. The vital signs of the patient were as follows: Blood pressure: 103/75 mmHg; Heart rate: 65 beats/min; Body temperature: 36˚C; Respiratory rate: 22/minute; Arterial blood gases; Partial pressure of oxygen: 48.6 mmHg, Partial pressure of carbon dioxide: 37.3 mmHg, A-a gradient=54.8 mmHg (norm <20 mmHg) Oxygen saturation: 90.8%. On neurological examination, the patient was lethargic with an eye-opening response to verbal and tactile stimuli, and her speech was incomprehensible. Right upper extremity was unresponsive to noxious stimuli. Motor strength was grade 2–3/5 in bilateral lower limbs. Plantar reflexes were extensor bilaterally. Respiratory sounds decreased in the basals. The

Cite this article as: Uz İ, Yalçınlı S, Efe M. Fat embolism syndrome after gluteal augmentation with hyaluronic acid: A case report. Ulus Travma Acil Cerrahi Derg 2020;26:960-962. Address for correspondence: İlhan Uz, M.D. Ege Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir, Turkey Tel: +90 232 - 390 23 20 E-mail: ilhan.uz@ege.edu.tr Ulus Travma Acil Cerrahi Derg 2020;26(6):960-962 DOI: 10.14744/tjtes.2019.08433 Submitted: 09.09.2019 Accepted: 06.12.2019 Online: 26.10.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

960

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Uz et al. Fat embolism syndrome after gluteal augmentation with hyaluronic acid

remainder of the systemic examination was unremarkable. There were no rashes on the body and no abnormal findings at the injection site. Laboratory analysis, bedside echocardiography, electrocardiogram, brain, and neck contrast-enhanced computerized tomography scans did not reveal any significant findings Thorax computed tomography showed bilateral ground-glass opacities and pleural effusion (see Fig. 1a). The multiple millimetric hyperintense foci observed in both cerebral hemispheres on the T2-weighted magnetic resonance images (MRI) were thought to be related to fat embolism (see Fig. 1b and c). The enoxaparin (6,000 IU (60 mg)/0.6 twice-daily by subcutaneous injection) and methylprednisolone (40 mg/intravenously) were administered to our patient with supportive treatment. Mechanical ventilation was not required. The patient was transferred to the intensive care unit with a diagnosis of FES and she was discharged from the hospital with healing after twenty days. The patient’s consent was obtained for this study.

DISCUSSION Although the most common cause is an orthopedic trauma, such as a femur fracture, fat embolism may also stem from thoracic traumas, burns, soft-tissue injuries, non-traumatic causes (such as pancreatitis, diabetes, osteomyelitis and panniculitis), and cosmetic procedures, such as liposuction, lipoinjection, and fat grafting.[4,5] In the literature, there are few cases reports describing fat embolism following buttock augmentation with different materials.[6] There are two theories on the pathogenesis of fat embolism. According to the theory of mechanical obstruction, either fragment of fatty tissue cause obstruction in the pulmonary microvascular system or smaller-sized oil droplets and free fatty acids that pass from the pulmonary circulation to the systemic circulation affect other organs without causing any respiratory symptom. Fat embolism can be the result of a paradoxical embolism (the embolus passes from a patent foramen oval and enters the arterial circulation) or a microembolism (small emboli pass through the pulmonary artery

(a)

(b)

(c)

into the pulmonary circulation and then to the systemic circulation). According to the biochemical theory, free fatty acids composed of neutral triglycerides cause damage to the capillary endothelium and stimulate cell migration and chemical mediator release from neutrophils. Complement system activation, chylomicrons, and the toxins released from leukocytes further increase the damage. In addition, intravascular coagulation occurs due to the release of thromboplastin from tissue fat.[7–9] Given its longer duration of effects, its biodegradability, and its biocompatibility, the use of HA has become widespread, especially for facial aesthetics in recent years. Mild or local complications are common after facial injection, but rarely some serious complications, such as skin necrosis, blindness, and cerebral infarction, may occur.[10–12] Cases of cerebral infarction following periocular or perinasal HA injection have been reported.[13,14] A review of 50 studies on buttock filler injections concluded that HA injection is effective but temporary and expensive. Of the 7834 patients who received buttock injections, only 69 patients had HA injections and nearly 40% of these experienced minor side effects, such as edema, itching, pain, and hematoma.[15–17] In a study involving more than 4000 patients who underwent breast augmentation using HA fillers, no serious complications were reported except for some local side effects.[18] Although given the absence of a gold standard diagnostic test or pathognomonic feature, several authors have proposed clinical diagnostic criteria (Gurd and Wilson’s criteria, Modified Gurd’s criteria, Schonfeld’s criteria).[19,20] According to these criteria, our patient is a rare case, diagnosed with fat embolism syndrome after gluteal augmentation with hyaluronic acid. She had no skin findings, but she was hypoxemic and lung computed tomography showed ground-glass densities and pleural effusion similar to CT features of FES.[21] She had a disorder of consciousness with multiple cerebral white lesions on brain MRI. There are no definitive treatments for FES. Although the administration of systemic corticosteroids and heparin are controversial, we preferred to use them.[22] The outcome of patients with FES is generally favorable. Pulmonary, neurological, and dermatologic manifestations of FES generally completely resolve.[3] Our patient recovered without a squeal.

Conclusion Figure 1. (a) Thorax computed tomography showed bilateral ground-glass opacities and pleural effusion. (b) Diffusion-weighted images (b=1.000) show multiple millimetric foci of diffusion restriction and ADC reduction in both cerebral hemispheres. (c) T2-weighted images demonstrate multiple millimetric hyperintense foci in both cerebral hemispheres.

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6

Patients presenting to the emergency department with altered mental status should be questioned for recent surgical or invasive aesthetic procedures. Fat embolism syndrome should be considered even if the patient has no petechial rash. The classic triad is not present in all patients. Although FES diagnosis is based on clinical features, imaging studies can 961

Uz et al. Fat embolism syndrome after gluteal augmentation with hyaluronic acid

help and speed up the diagnosis. Brain MRI, including diffusion-weighted sequences and lung CT, should be the imaging modality of choice in these patients. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: İ.U.; Design: İ.U., S.Y.; Supervision: İ.U., S.Y.; Resource: İ.U., M.E.; Materials: İ.U., S.Y., M.E.; Data: İ.U., S.Y., M.E.; Interpretation: İ.U., S.Y., M.E.; Literature search: İ.U., S.Y.; Writing: İ.U.; Critical revision: İ.U. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Stein PD, Yaekoub AY, Matta F, Kleerekoper M. Fat embolism syndrome. Am J Med Sci 2008;336:472–7. 2. Rothberg DL, Makarewich CA. Fat Embolism and Fat Embolism Syndrome. J Am Acad Orthop Surg 2019;27:e346–55. 3. Scarpino M, Lanzo G, Lolli F, Grippo A. From the diagnosis to the therapeutic management: cerebral fat embolism, a clinical challenge. Int J Gen Med 2019;12:39–48. 4. de Lima E Souza R, Apgaua BT, Milhomens JD, Albuquerque FT, Carneiro LA, Mendes MH, et al. Severe fat embolism in perioperative abdominal liposuction and fat grafting. Brazilian J Anesthesiology (Elsevier) 2016;66:324–8. 5. Ross RM, Johnson GW. Fat embolism after liposuction. Chest 1988;93:1294–5. 6. Mendoza-Morales RC, Camberos-Neva EV, Luna-Rosas A, Garces-Ramirez L, De la Cruz F, Garcia-Dolores F. A fatal case of systemic fat embolism resulting from gluteal injections of vitamin e for cosmetic enhancement. Forensic Science International 2015;259:e1–4. 7. Hulman G. The pathogenesis of fat embolism. J Pathology 1995;176:3–9. 8. Pell AC, Hughes D, Keating J, Christie J, Busuttil A, Sutherland GR. Brief report: fulminating fat embolism syndrome caused by paradoxical embo-

lism through a patent foramen ovale. N Engl J Med 1993;329:926–9. 9. Sulek CA, Davies LK, Enneking FK, Gearen PA, Lobato EB. Cerebral microembolism diagnosed by transcranial Doppler during total knee arthroplasty: correlation with transesophageal echocardiography. Anesthesiology 1999;91:672–6. 10. Park TH, Seo SW, Kim JK, Chang CH. Clinical experience with hyaluronic acid-filler complications. J Plast Reconstr Aesthet Surg 2011;64:892–6. 11. Kim DW, Yoon ES, Ji YH, Park SH, Lee BI, Dhong ES. Vascular complications of hyaluronic acid fillers and the role of hyaluronidase in management. J Plast Reconstr Aesthet Surg 2011;64:1590–5. 12. Wang Q, Zhao Y, Li H, Li P, Wang J. Vascular Complications After Chin Augmentation Using Hyaluronic Acid. Aesthetic Plast Surg 2018;42:553–9. 13. Ansari ZA, Choi CJ, Rong AJ, Erickson BP, Tse DT. Ocular and cerebral infarction from periocular filler injection. Orbit 2019;38:322–4. 14. Kim EG, Eom TK, Kang SJ. Severe visual loss and cerebral infarction after injection of hyaluronic acid gel. J Craniofac Surg 2014;25:684–6. 15. Oranges CM, Tremp M, di Summa PG, Haug M, Kalbermatten DF, Harder Y, et al. Gluteal Augmentation Techniques: A Comprehensive Literature Review. Aesthet Surg J 2017;37:560–9. 16. Camenisch CC, Tengvar M, Hedén P. Macrolane for volume restoration and contouring of the buttocks: magnetic resonance imaging study on localization and degradation. Plast Reconstr Surg 2013;132:522–9e. 17. De Meyere B, Mir-Mir S, Peñas J, Camenisch CC, Hedén P. Stabilized hyaluronic acid gel for volume restoration and contouring of the buttocks: 24-month efficacy and safety. Aesthetic Plast Surg 2014;38:404–12. 18. Ishii H, Sakata K. Complications and management of breast enhancement using hyaluronic acid. Plast Surg (Oakv) 2014;22:171–4. 19. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br 1970;52:732–7. 20. Schonfeld SA, Ploysongsang Y, DiLisio R, Crissman JD, Miller E, Hammerschmidt DE, et al. Fat embolism prophylaxis with corticosteroids. A prospective study in high-risk patients. Ann Intern Med 1983;99:438– 43. 21. Newbigin K, Souza CA, Torres C, Marchiori E, Gupta A, Inacio J, et al. Fat embolism syndrome: State-of-the-art review focused on pulmonary imaging findings. Respir Med 2016;113:93–100. 22. Weinhouse GL. Fat Embolism Sydrome. UpToDate (Online) 2019. Available from: https://www.uptodate.com/contents/fat-embolism-syndrome#H2736501445. Accessed 05 December, 2019.

OLGU SUNUMU - ÖZET

Hyalüronik asit ile kalça dolgusu sonrası yağ emboli sendromu olgusu Dr. İlhan Uz, Dr. Sercan Yalçınlı, Dr. Mehmet Efe Ege Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir

Yağ embolisi sendromu, klasik olarak akut solunum yetmezliği, nörolojik anormallikler ve peteşiyal döküntü kombinasyonu ile ortaya çıkar. Kırk altı yaşında kadın hasta acil servise ajitasyon, bilinç değişikliği ve uykuya meyil şikayetleri ile başvurdu. Hastanın acil servise gelmeden saatlerce önce bir güzellik merkezinde, kalçalarına estetik amaçlı hyalüronik asit (HA) enjeksiyonu yapıldığı öğrenildi. Cilt bulguları yoktu ancak hipoksemi ile akciğer bilgisayarlı tomografisinde (BT) iki taraflı buzlu cam opasiteleri ve plevral efüzyon bulguları mevcuttu, ayrıca beyin manyetik rezonans görüntülerinde (MRG) çok sayıda beyaz lezyon vardı. Acil servise bilinçte ani değişiklikler ile başvuran hastalar, geçirilmiş cerrahi veya invaziv estetik prosedürler için sorgulanmalıdır. Yağ embolisi sendromu, hastanın peteşial döküntüleri olmasa bile düşünülmelidir. Beyin MR ve akciğer BT bu hastalarda tercih edilen görüntüleme yöntemi olmalıdır. Anahtar sözcükler: Acil tıp; hyalüronik asit enjeksiyonu; yağ emboli sendromu. Ulus Travma Acil Cerrahi Derg 2020;26(6):960-962

962

doi: 10.14744/tjtes.2019.08433

Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 6