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ISSN 1306 - 696X

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

Volume 22 | Number 5 | September 2016

www.tjtes.org


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

www.tjtes.org


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

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

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

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

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

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

p-ISSN 1306-696x • e-ISSN 1307-7945 • Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır.) Publisher (Yayımcı): KARE Yayıncılık (KARE Publishing) • www.kareyayincilik.com • Design (Tasarım): Ali Cangül • Graphics (Grafikler): Edibe Çomaktekin • Linguistic Editor (İngilizce Editörü): Suzan Atwood • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): September (Eylül) 2016 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE P U B L I S H I N G

www.tjtes.org


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

tion, called “Upload Your Files”.

As from 2001, the journal is indexed in Index Medicus and Medline, as from 2005 in Excerpta Medica and EMBASE, as from 2007 in Science Citation Index Expanded (SCI-E) and Journal Citation Reports / Science Edition, and as from 2008 in Index Copernicus. Our impact factor in SCI-E indexed journals is 0.5. It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PUBMED.

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

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

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

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


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

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


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

Number - Sayı 5 September - Eylül 2016

Contents - İçindekiler Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 405-411 Pulmonary microvascular dysfunction and pathological changes induced by blast injury in a rabbit model Bir tavşan modelinde blast travmasıyla indüktlenen pulmoner mikrovasküler disfonksiyon ve patolojik değişiklikler Wu SY, Han GF, Kang JY, Zhang LC, Wang AM, Wang JM 412-416 A new experimental burn model with an infrared heater İnfrared ısıtıcı kullanarak oluşturulan yeni bir deneysel yanık modeli Güzey S, Dal AD, Şahin İ, Nişancı M, Yavan İ 417-422 Protective effect of betaine against burn-induced pulmonary injury in rats Sıçanlarda yanığa bağlı olarak gelişen akciğer hasarına karşı betain’in koruyucu etkisi Şehirli AÖ, Satılmış B, Tetik Ş, Çetinel Ş, Yeğen B, Aykaç A, Şener G

Original Articles - Orijinal Çalışma 423-431 Efficiacy of resveratrol and quercetin after experimental spinal cord injury Deneysel spinal kord travması sonrası Resveratrol ve Quercetin’in etkinliğinin araştırılması Çiftçi U, Delen E, Vural M, Uysal O, Turgut Coşan D, Baydemir C, Doğaner F 432-436 Intraorbital foreign bodies: Clinical features and outcomes of surgical removal İntraorbital yabancı cisimler: Klinik özellikleri ve cerrahi çıkartım sonuçları Dolar Bilge A, Yılmaz H, Yazıcı B, Naqadan F 437-440 Traumatic wound dehiscence after penetrating keratoplasty Penetran keratoplasti sonrası travmatik yara ayrılması Barut Selver Ö, Palamar M, Eğrilmez S, Yağcı A 441-448 Management of perforation after endoscopic retrograde cholangiopancreatography (ERCP) Endoskopik retrograd kolanjiopankreatikografiye (ERKP) bağlı perforasyonların tedavisi Tavusbay C, Alper E, Gökova M, Kamer E, Kar H, Atahan K, Özşay O, Gür Ö, Cin N, Çapkınoğlu E, Durak E 449-456 Evaluation of patients diagnosed with acute blunt aortic injury and their bedside plain chest radiography in the emergency department: A retrospective study Acil serviste akut künt travmatik aortik yaralanma tanısı alan olguların geriye dönük incelenmesi ve yatakbaşı akciğer grafi görüntülerinin değerlendirilmesi Karbek Akarca F, Korkmaz T, Çınar C, Çakal ED, Ersel M 457-465 The effect of body mass index on trauma severity and prognosis in trauma patients Travma hastalarında vücut kitle indeksinin (VKİ) travma şiddeti ve prognoza etkisi Durgun HM, Dursun R, Zengin Y, Özhasenekler A, Orak M, Üstündağ M, Güloğlu C 466-470 Evaluation of the open and laparoscopic appendectomy operations with respect to their effect on serum IL-6 levels Açık ve laparoskopik apendektomi ameliyatlarının serum IL-6 düzeylerine etkisi açısından değerlendirilmesi Bartın MK, Kemik Ö, Çaparlar MA, Bostancı MT, Öner MÖ

Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

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

Number - Sayı 5 September - Eylül 2016

Contents - İçindekiler

471-476 Pre-operative stool analysis for intestinal parasites and fecal occult blood in patients with acute appendicitis Akut apandisit hastalarında gaitada gizli kan ve intestinal parazitler için ameliyat öncesi gaita analizi Hatipoğlu S, Lök U, Gülaçtı U, Çelik T 477-482 How safe is the semi-sterile technique in the percutaneous pinning of supracondylar humerus fractures? Suprakondiler humerus kırıklarının perkütan tellenmesinde kısmi steril teknik ne kadar güvenlidir? Turgut A, Önvural B, Kazımoğlu C, Bacaksız T, Kalenderer Ö, Ağuş H 483-488 Comparison of lateral versus triceps-splitting posterior approach in the surgical treatment of pediatric supracondylar humerus fractures Pediatrik suprakondiler humerus kırıklarının tedavisinde trisepsi kesen posterior ve lateral yaklaşımın karşılaştırılması Türkmen F, Toker S, Kesik K, KorucuİH, Acar MA 489-494 Yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesi Determination of subacute and chronic period sleep quality in burn patients Pazar B, İyigün E, Şahin İ

Case Reports - Olgu Sunumu 495-497 Early post-traumatic splenic arteriovenous fistula in the pancreatic arcade: Diagnosis by volume-rendered 3D reconstruction images Pankreasta erken evrede oluşan posttravmatik splenik arteriyovenöz fistül: Üç boyutlu volüm rekonstrüksiyon görüntüleriyle tanı Tsurukiri J, Sano H, Akira H, Kaneko N 498-501 A rare disease mimics postoperative bile leakage: Invasive aspergillosis Ameliyat sonrası safra kaçağını taklit eden nadir bir hastalık: İnvaziv aspergillozis Yazar FM, Urfalıoğlu A, Boran ÖF, Sayar H, Kanat BH, Emre A, Cengiz E, Bülbüloğlu E 502-504 Akut apandisiti taklit eden karın ön duvarı yerleşimli preperitoneal saplı lipom torsiyonu Torsion of a preperitoneal pedunculated lipoma of anterior abdominal wall mimicking acute appendicitis Özemir İA, Orhun K, Bilgiç Ç, Eren T, Bayraktar B, Zemheri E, Ekinci Ö, Alimoğlu O 505-508 Süt çocuğunda anorektal cerrahi sonrası gelişen Fournier’s gangreni: İki olgu sunumu Fournier’s gangrene after anorectal surgery in infant: Two case reports Sütçü M, Duran Şık G, Gün F, Somer A, Salman N

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Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


EXPERIMENTAL STUDY

Pulmonary microvascular dysfunction and pathological changes induced by blast injury in a rabbit model Si-Yu Wu, M.D.,*,1 Geng-Fen Han, M.D.,*,1 Jian-Yi Kang, M.D.,2 Liang-Chao Zhang, M.D.,2 Ai-Min Wang, M.D., Ph.D.,1 Jian-Min Wang, M.D., Ph.D.2,3 1

Department of Orthopedics, Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China

The 6th Department of Research Institute of Field Surgery and Daping Hospital, Third Military Medical University, Chongqing, 400042, PR China

2 3

State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing, 400042, PR China

ABSTRACT BACKGROUND: Vascular leakage has been proven to play a critical role in the incidence and development of explosive pulmonary barotrauma. Quantitatively investigated in the present study was the severity of vascular leakage in a gradient blast injury series, as well as ultrastructural evidence relating to pulmonary vascular leakage. METHODS: One hundred adult male New Zealand white rabbits were randomly divided into 5 groups according to distance from the detonator (10 cm, 15 cm, 20 cm, 30 cm, and sham control). Value of pulmonary vascular leakage was monitored by a radioactive 125I-albumin labeling method. Pathological changes caused by the blast wave were examined under light and electron microscopes. RESULTS: Transcapillary escape rate of 125I-albumin and residual radioactivity in both lungs increased significantly at the distances of 10 cm, 15 cm, and 20 cm, suggesting increased severity of vascular leakage in these groups. Ultrastructural observation showed swelling of pulmonary capillary endothelial cells and widened gap between endothelial cells in the 10-cm and 15-cm groups. CONCLUSION: Primary blast wave can result in pulmonary capillary blood leakage. Blast wave can cause swelling of pulmonary capillary endothelial cells and widened gap between endothelial cells, which may be responsible for pulmonary vascular leakage. Keywords: Blast injury; permeability; pulmonary dysfunction; vascular leakage.

INTRODUCTION Blast injuries are a series of minor, major, or lethal traumas that may lead to dysfunctions in pulmonary, gastrointestinal, and auditory systems.[1–5] In the past, the majority of blast injuries were sustained during military conflict, or industrial or mining accidents. However, explosions in different kinds of *These authors contributed equally to this work.

Address for correspondence: Ai Min Wang, M.D and Jian Min Wang, M.D. Ai Min Wang: Department of Orthopedics, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China. Tel: +86 – 023 – 68757936 E-mail: trauma3@163.com Jian Min Wang: 6th Department of Research Institute of Field Surgery and State Key Laboratory of Trauma and Burn and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing 400042, China. E-mail: jmwangcq@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):405–411 doi: 10.5505/tjtes.2015.06005 Copyright 2016 TJTES

Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

terrorist attacks have become the leading cause of blast injuries. It has been reported that blast injuries sustained during terrorist attacks increased 4-fold from 1999 to 2006, worldwide.[6] Therefore, investigations into the mechanism of blast injury are imperative, as they may aid in exploring solutions for blast injury patients. Pulmonary barotrauma is one of the most critical injuries in civilian or military blast settings. It has been shown that pathological characteristics of explosive pulmonary barotrauma include alveolar hemorrhage, interstitial edema, and alveolar septa rupture. Such pathological changes are always lethal, due to impairment of gas exchange capacity.[2–4,6] Thus far, several contributing factors for pulmonary blast injury have been identified, including direct tissue damage, progressive vascular leakage, and inflammatory changes. In particular, vascular leakage has been shown to play a critical role in the incidence and development of explosive pulmonary barotraumas.[7–12] Although the existence and significance of vascular leakage in pulmonary blast injury has been confirmed, there has been insufficient quantitative investigation into pulmonary vascular leakage. In addition, ultrastructural evidence of pulmonary vascular leakage has not been identified. Therefore, the pri405


Wu et al. Pulmonary microvascular dysfunction induced by blast

mary aim of the present study was to quantitatively investigate the severity of vascular leakage in a gradient blast wave series. The secondary aim was to explore ultrastructural evidence of pulmonary vascular leakage.

MATERIALS AND METHODS Animal Model of Blast Injury One hundred adult male New Zealand White rabbits weighing from 2.0 to 2.5 kg were provided by the Experimental Animal Center of the Third Medical University. All experimental protocols were approved by the Institutional Animal Care and Research Advisory Committee, and were performed in accordance with the National Institutes of Health Guidelines for Animal Use and Care. The animals were randomly divided into 5 groups (n=20), including 1 group that served as sham control. Each animal was anesthetized by intravenous injection of 3.0% pentobarbital-sodium at a dose of 30 mg/kg, and received an intravenous injection of 2 mg/ kg carprofen to prevent pain. A 10-cm×10-cm region of the surface of the xiphoid process was shaved, and the rabbit was fixed on a specially designed plate, lying on the right side to prevent movement in response to blast impact. Electrocardiogram (ECG) was recorded with a CardiMax FX-7202 electrocardiograph (Fukuda Denshi Co. Ltd., Tokyo, Japan), with a vertical calibration of 10 mm/mV, and a horizontal paper speed of 25 mm/second. Printouts were made prior to detonation and every 10 min after detonation, or as necessary. The blast wave was generated by detonator containing 0.9 g trimethylene trinitramine (RDX) and 0.4 g diazodinitrophenol (DDNP; No. 845 Factory, Chongqing, China). The detonator was placed at the same horizontal level as the thoracoabdominal midline of the animal, pointed at the surface of the xiphoid process. In order to achieve the gradient blast injury, the detonator was set at 10 cm, 15 cm, 20 cm and 30 cm from the animals. In each group, 5 rabbits were distributed for histological observation, while the others were subjected to permeability measurement. The animals of the control group underwent the same protocols, with the exception of detonation. Certain necessary emergency treatments were conducted following detonation, such as chest compressions and methods to ensure that the respiratory tract was unobstructed.

Determination of Blast Wave Following anesthetization by pentobarbital-sodium, each animal was placed on a specially designed wooden desk, with left forelimb secured tightly to expose the chest and abdomen. The detonator was placed vertically at the series of distances (10 cm, 15 cm, 20 cm and 30 cm), in alignment with the xiphoid process. A SK-902 piezoelectricity pressure sensor ( Jili Electron Machine Factory, Yangzhou, China) was attached to the right chest. The sensor was connected to a SK6882 charge amplifier ( Jili Electron Machine Factory, Yangzhou, China). Real-time signal was recorded 406

and processed by a HP54501A data-recording oscillograph (Hewlett-Packard Inc., Palo Alto, CA, USA) during detonation. Characteristic parameters of blast wave included peak pressure, duration of positive pressure, and the time of pressure-to-peak.

Pulmonary Microvascular Permeability Severity of vascular leakage in a series of blast injuries was monitored by a radioactive 125I-albumin labeling method. After induction of anesthesia, blood samples (3 ml) of each animal were drawn into vacutainer tubes containing ethylene diamine tetraacetic acid (EDTA) through the right jugular vein of the rabbits. Each blood sample was centrifuged at 10,000 r/min for 10 min, hematocrit (HCT) value was determined using a ZJ2000 blood cell analyzer (Shounuote Scientific Instrument, Inc., Jiangxi, China), and 125I-albumin (20 μCi/kg) was administered through the internal jugular vein. After 5 minutes, 1 ml of blood from animals in each group (n=15) was obtained to measure radioactivity (counts/minute, min-1). Thirty minutes after detonation, the process was repeated. While blood was released from the femoral artery, 500 ml 0.9% sodium solution was injected into the internal jugular vein. Thereafter, each rabbit was sacrificed to acquire value of radioactivity in both lungs. On the assumption that total red cell volume would be constant throughout the experiment, the transcapillary escape rate of total 125I-albumin (R1) and the rate of residual-radioactivity (R2) in both lungs were acquired using the following equations:

R1=(1−(Hct1×r2)/(Hct2×r1)−r4/rt)×100% (1) R2=r3/(Wt×r2)×100% (2) The symbol rt stands for total radioactivity before injury, r1 for radioactivity per ml blood before injury, r2 for radioactivity per ml blood after injury, r3 for residual radioactivity of lung tissue after injury, r4 for radioactivity of blood drawn from the femoral artery, Wt for the weight of tissue, HCT1 for HCT before injury, and HCT2 for HCT after injury.

Histological Study Following 30 minutes of observation, the animals were sacrificed via overdose of pentobarbital until ECG became isoelectric. Lung tissue specimens of 25 rabbits (n=5 in each group, 5 groups) were immediately fixed in 2.5% glutaraldehyde. The specimens were dehydrated in an ascending grade of ethanol, cleared in xylene, and embedded in paraffin wax. Serial sections of 5-mm thickness were obtained using rotatory microtome. Deparaffinized sections were routinely stained with haematoxylin and eosin (HE). Photomicrographs of each slide were obtained using digital research photographic microscope (IX50; Olympus Co., Ltd., Tokyo, Japan).

Ultrastructural Observation Ultrastructural alterations were investigated with electron microscopy. Harvested lung samples were post-fixed by 1% Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Wu et al. Pulmonary microvascular dysfunction induced by blast

evaluate the severity of vascular leakage by calculating the variation of total radioactivity in blood. It was shown that the transcapillary escape rate of 125I-albumin significantly increased after injury at the distances of 10 cm, 15 cm, and 20 cm, suggesting an increase of vascular leakage in these groups (p<0.05, Table 2). Little influence on the transcapillary escape rate of 125I-albumin was found in rabbits at the distance of 30 cm (p>0.05, Table 2). In particular, the transcapillary escape rate of 125I-albumin at the distance of 10 cm was significantly higher than rates at the distances of 15 cm, 20 cm, and 30 cm. This outcome demonstrated that higher intensity of blast wave can result in more severe vascular leakage (p<0.05, Table 2).

osmium tetroxide in 0.1-M sodium cacodylate buffer (pH 7.3) for 1 hour at room temperature. They were then dehydrated in ethanol and embedded in resin. Ultra-thin sections of lung samples were prepared and stained with uranyl acetate and lead citrate. They were then examined under a transmission electron microscope (TECNAI 10; Philips Healthcare, Inc., Eindhoven, Netherlands). Morphometric evaluation was conducted by an examiner who had not been informed of the experiment’s design.

Statistical Analysis Values are expressed as mean±SD. Following test for normalcy of distribution, data were analyzed with one-way analysis of variance (ANOVA) using the SPSS software package (version 13.0; SPSS Inc., Chicago, IL, USA). When significant overall difference among groups was determined, Tukey’s post hoc test was used to perform pairwise comparison, and p<0.05 was considered statistically significant.

Residual radioactivity in both lungs was measured to reflect the amount of 125I-albumin leaking into the interstitial space through the damaged microvessel in the lung. The data showed that residual radioactivity significantly increased following injury at the distances of 10 cm, 15 cm, and 20 cm, suggesting an increased amount of vascular leakage in these groups (p<0.05, Table 2).

RESULTS

Animal Experiment and Pathology Results

Distance Decay of Blast Wave in Air

All animals survived the 30-minute observation period. Body surface of injured animals suffered burn and subcutaneous hemorrhage without penetrability trauma, while foliated hemorrhage was observed in the lungs. Representative photographs of HE-stained sections are shown in Fig. 1. Observed in the 10-cm group were alveolar and interstitial hemorrhage, pulmonary interstitial edema, multifocal alveolar septum fracture, focal bullae formation, and necrosis or loss of pulmonary capillary endothelial cell in lumen (Fig. 1b, c). In the 15-cm group, red blood cells were found in the alveolar lumen, and the edema of the alveolar epithelial cell

The distance decay of the blast wave was recorded by pressure sensor. Data regarding distances from the detonator are displayed in Table 1. Pressure peak of blast wave and time required for pressure rise both decreased as the distance to the detonator increased, while the duration of positive pressure increased.

Blast Wave Increased Pulmonary Microvascular Permeability Transcapillary escape rate of

I-albumin was measured to

125

Table 1. Blast wave pressure at various distances from the detonator in air (Mean±SD) Distance (cm)

n

Peak pressure (kPa)

Duration of positive pressure (μs)

Pressure rise time (μs)

10

15 1108.30±173.75

121±14

24.0±7.5

15

15 381.50±46.64

152±61

22.0±4.7

20

15 175.43±22.34

170±24

18.0±4.3

30

15 68.50±13.57

209±53

12.0±3.6

Table 2. Change of rate of escaped and retained 125I-albumin radiation in lung tissue after trauma caused by explosive blast at various distances from explosive center (Mean±SD, n=15) Group

Rate of

I-albumin escaped (%)

125

Remained radiation (counts/min/g) Left lung

Right lung

Control

26.43±7.49

4080.58±971.64 4628.11±409.82

10 cm

41.79±6.69 7496.94±729.48** 6189.36±583.80**

15 cm

39.58±8.40** 5579.31±719.32** 6173.80±744.81**

**

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407


Wu et al. Pulmonary microvascular dysfunction induced by blast

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

Figure 1. Representative HE micrographs of impaired lungs in normal group (a) and in blast injury groups at 10 cm (b, c), 15 cm (d, e), 20 cm (f, g), and 30 cm (h, i). Original magnifications: 100Ă&#x2014;(a, b, d, f, h); 200Ă&#x2014;(c, e, g, i).

and alveolar-interstitial. Focal fracture of the alveolar septum, interstitial capillary congestion, and lymphocyte infiltration were also noted (Fig. 1d, e). In the 20-cm group, red blood cells were found in the alveolar lumen, and alveolar epithelial cell edema and spotty necrosis were also noted (Fig. 1f, g). In the 30-cm group, only scattered red blood cells were found in the alveolar lumen (Fig. 1f, h).

Ultrastructural Evidence of Impaired Pulmonary Permeability Following blast injury, ultrastructural changes were found with transmission electron microscopy. In the 10-cm group, it was observed that pulmonary microvascular endothelial cells were generally swollen (Fig. 2b). Necrosis was also found in some endothelial cells (Fig. 2c). In the 15-cm group, the gap between pulmonary microvascular endothelial cells was significantly widened (Fig. 2d). Red blood cells had escaped through the alveolar wall, and pulmonary capillary endothelial cell swelling was noted (Fig. 2e). Neutrophils were incarcerated in the endovascular system (Fig. 2f). In the 20-cm group, pulmonary capillary endothelial cell swelling was noted (Fig. 408

2g,h). In the 30-cm group, no obvious ultrastructural change was observed (Fig. 2i).

DISCUSSION Quantitatively investigated in the present study was the severity of vascular leakage in a series of gradient blast injuries. In addition, ultrastructural evidence relating to pulmonary vascular leakage was explored. It was found that blood condensed following blast injury. The amount of vascular leakage decreased as the distance to the explosion center increased. In addition, the pulmonary capillary endothelial cells swelled, died, or were lost, and the gap between pulmonary microvascular endothelial cells widened. These phenomena may be responsible, at least in part, for the increased amount of pulmonary vascular leakage after blast injury. Blast wave was generated by detonator containing RDX and DDNP, which are widely used in the improvised explosive devises of terrorist attacks.[1,6,12] The detonators were placed at a series of distances (10 cm, 15 cm, 20 cm, and 30 cm) to generate waves of varying intensity. It was found that peak presUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Wu et al. Pulmonary microvascular dysfunction induced by blast

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

Figure 2. Representative ultrastructural appearances of impaired lungs in normal group (a) and in blast injury groups at 10 cm (b, c), 15 cm (dâ&#x20AC;&#x201C;f), 20 cm (g, h), and 30 cm (i). a: normal lung; b: swelling of pulmonary microvascular endothelial cells with nuclear swelling; c: necrosis of pulmonary microvascular endothelial cells; d: significantly widened gaps between pulmonary microvascular endothelial cells; e: red blood cells escaped through the alveolar wall; f: swelling observed in the pulmonary capillary endothelial cells and neutrophils incarcerated in the endovascular system; g and h: pulmonary capillary endothelial cell swelling; i: no cell swelling was observed.

sure decreased as distance increased, while duration of positive pressure and time required for pressure rise remained relatively constant. This observation was in accordance with findings of previous studies[2,11,13,14] and matched the characteristics of blast wave transmission in air. Blast wave caused plasma loss in the pulmonary endothelium, which was monitored by the radioactive 125I-albumin labeling method. It was found that a blast wave of higher intensity resulted in greater pulmonary vascular leakage. Such a finding was evidenced by higher rates of 125I-albumin escape and greater residual radioactivity in the lungs of rabbits in the 10-cm and 15-cm groups. The extent of pulmonary vascular leakage was highly correlated with damage to pulmonary endothelial cells. Under a relatively low pressure (such as that of the 20-cm group), pulmonary capillary endothelial cells were somewhat swollen, but the gap between endothelial cells was not affected. However, under higher pressures (such as those of the 10-cm and 15-cm groups), the gap between pulmonary capillary endothelial cells widened, and more severe damage was observed. It was clear that blast waves had destroyed pulmonary capillary endothelial cells, and that cells had widened, resulting in vascular leakage. Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

The pulmonary endothelium participates in the exchange of water and solute between the blood and the interstitium. In normal conditions, a small amount of fluid is filtered across the endothelial monolayer and drained by the lymphatic system. Fluid filtration is limited by endothelium continuity, with multiple connections between the cells called tight and adherens junctions.[15,16] Thus, water and solute flux is strictly regulated, occurring passively between endothelial cells, termed the paracellular pathway, and driven by the hydrostatic pressure gradient between intravascular and perivascular space. [16â&#x20AC;&#x201C;18] Albumin and other macromolecules are actively transported through endothelial cells by an elaborate vesicle system known as the transcellular pathway.[16,19â&#x20AC;&#x201C;21] In the present study, swollen pulmonary capillary endothelium and widened gap between endothelial cells were observed following injury. Water and solute may easily leak out of the capillary vessel through the widened gap, a reverse result of blood condensation. Therefore, the widened gap and swollen endothelial cells that resulted from the blast wave may be the ultrastructural basis for the increased severity of vascular leakage and blood condensation. Vascular leakage was a significant cause of pulmonary edema. 409


Wu et al. Pulmonary microvascular dysfunction induced by blast

It was found that the gap between the pulmonary microvascular endothelial cells widened significantly, and that red blood cells had escaped through the alveolar wall, a significant cause of pulmonary hemorrhage. Blast overpressure simultaneously exerts compressive forces on the extravascular fluid, driving it into the alveolar space and causing pulmonary edema and alveolar hemorrhage.[22] It has been demonstrated in animal studies that edema and hemorrhage increase lung weight and correlate with blast peak pressure and mortality.[23] Therefore, it is very necessary to manage pulmonary edema and hemorrhage. It has also been demonstrated that administration of hemostatic nanoparticles led to significant improvement in short-term survival, and that no complications were observed.[24] Blast injury often leads to severe systemic inflammatory response and multiple organ dysfunction. Acute lung injury (ALI) and its most severe extreme, acute respiratory distress syndrome (ARDS) refer to increased permeability in pulmonary edema caused by a variety of pulmonary or systemic insults.[25] TNF-α and IL-6 are involved in the pathogenesis and development of ARDS in blast injury.[26] Haemoxygenase-1 activated by hemin was reported to increase survival in rats with blast lung, possibly involving an anti-inflammatory mechanism,[27] while administration of antioxidant N-acetylcysteine amide was shown to facilitate lung recovery from inflammatory damage, protection that could be vital in situations of more severe blunt lung trauma with progression to ALI/ ARDS.[28] In a clinical scenario, studies have shown improved outcome of severe sepsis/systemic inflammatory response with the use of activated protein C, steroid replacement, and aggressive control of blood glucose following blast injury.[29] ALI and ARDS are usually accompanied by hypoxemia and the need for mechanical ventilation. The risk of air embolism from positive pressure ventilation has led to a variety of methods of ventilation, such as limited peak inspiratory pressure with permissive hypercapnia, intermittent mechanical ventilation, and high-frequency ventilation, to varying degrees of success.[30] Pneumothorax as a result of lung rupture is the chief reason for early death and dysfunction of the circulatory system, and is also an important cause of early death. [26] Endotracheal intubation should be instituted to maintain the artificial ventilation required in cases of pulmonary blast injury. It is worth noting that positive pressure from mechanical ventilation may cause rapid increase in pneumothorax size by inducing lung tissue disruption and increasing air leakage into the pleural space.[31] In conclusion, it was demonstrated in the present study that primary blast wave can result in blood condensation and increase in pulmonary microvascular permeability. In addition, not only can blast wave cause pulmonary capillary endothelial cell swelling, but it can also widen the gap between endothelial cells, which may cause increasing severity of pulmonary vascular leakage and blood condensation. The present find410

ings provide novel histological evidence of pulmonary blast injury, which may aid in better understanding of the mechanism of this critical disease.

Acknowledgement The present work was supported by grants from the National Natural Science Foundation of China (No: 10776038). The authors would like to thank Mr. Chen Ziqiang, Li Qinlong, M.D., and Diao Xinwei, M.D. for their excellent work in the laboratory during the histological study. Conflict of interest: None declared.

REFERENCES 1. DePalma RG, Burris DG, Champion HR, Hodgson MJ. Blast injuries. N Engl J Med 2005;352:1335–42. 2. Elsayed NM. Toxicology of blast overpressure. Toxicology 1997;121:1– 15. 3. Leibovici D, Gofrit ON, Stein M, Shapira SC, Noga Y, Heruti RJ, et al. Blast injuries: bus versus open-air bombings--a comparative study of injuries in survivors of open-air versus confined-space explosions. J Trauma 1996;41:1030–5. 4. Mayorga MA. The pathology of primary blast overpressure injury. Toxicology 1997;121:17–28. 5. Wightman JM, Gladish SL. Explosions and blast injuries. Ann Emerg Med 2001;37:664–78. 6. Wolf SJ, Bebarta VS, Bonnett CJ, Pons PT, Cantrill SV. Blast injuries. Lancet 2009;374:405–15. 7. Avidan V, Hersch M, Armon Y, Spira R, Aharoni D, Reissman P, et al. Blast lung injury: clinical manifestations, treatment, and outcome. Am J Surg 2005;190:927–31. 8. Chaloner E. Blast injury in enclosed spaces. BMJ 2005;331:119–20. 9. Crabtree J. Terrorist homicide bombings: a primer for preparation. J Burn Care Res 2006;27:576–88. 10. Eckert MJ, Clagett C, Martin M, Azarow K. Bronchoscopy in the blast injury patient. Arch Surg 2006;141:806–11. 11. Elsayed NM, Gorbunov NV. Pulmonary biochemical and histological alterations after repeated low-level blast overpressure exposures. Toxicol Sci 2007;95:289–96. 12. Pizov R, Oppenheim-Eden A, Matot I, Weiss YG, Eidelman LA, Rivkind AI, et al. Blast lung injury from an explosion on a civilian bus. Chest 1999;115:165–72. 13. Bauman RA, Elsayed N, Petras JM, Widholm J. Exposure to sublethal blast overpressure reduces the food intake and exercise performance of rats. Toxicology 1997;121:65–79. 14. Rosenfeld JV, Ford NL. Bomb blast, mild traumatic brain injury and psychiatric morbidity: a review. Injury 2010;41:437–43. 15. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 2004;84:869–901. 16. Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev 2006;86:279–367. 17. Lucas R, Verin AD, Black SM, Catravas JD. Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochem Pharmacol 2009;77:1763–72. 18. Vandenbroucke E, Mehta D, Minshall R, Malik AB. Regulation of endothelial junctional permeability. Ann N Y Acad Sci 2008;1123:134–45. 19. Minshall RD, Malik AB. Transport across the endothelium: regulation of endothelial permeability. Handb Exp Pharmacol 2006;(176 Pt 1):107– 44.

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Wu et al. Pulmonary microvascular dysfunction induced by blast 20. Minshall RD, Sessa WC, Stan RV, Anderson RG, Malik AB. Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol 2003;285:L1179–83. 21. Predescu SA, Predescu DN, Malik AB. Molecular determinants of endothelial transcytosis and their role in endothelial permeability. Am J Physiol Lung Cell Mol Physiol 2007;293:L823–42. 22. Crabtree J. Terrorist homicide bombings: a primer for preparation. J Burn Care Res 2006;27:576–88. 23. Elsayed NM. Toxicology of blast overpressure. Toxicology 1997;121(1):1–15. 24. Lashof-Sullivan MM, Shoffstall E, Atkins KT, Keane N, Bir C, VandeVord P, et al. Intravenously administered nanoparticles increase survival following blast trauma. Proc Natl Acad Sci U S A 2014;111:10293–8. 25. Maniatis NA, Kotanidou A, Catravas JD, Orfanos SE. Endothelial pathomechanisms in acute lung injury. Vascul Pharmacol 2008;49:119– 33.

26. Fan CX, Zhang ZP, Cheng QS, Li YZ, Zhu YF, Wang J, et al. Experimental study on acute respiratory distress syndrome and analysis of relevant factors in rabbits subjected to thoracic blast trauma. [Article in Chinese] Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2011;23:243–6. [Abstract] 27. Chavko M, Prusaczyk WK, McCarron RM. Protection against blastinduced mortality in rats by hemin. J Trauma 2008;65:1140–5. 28. Chavko M, Adeeb S, Ahlers ST, McCarron RM. Attenuation of pulmonary inflammation after exposure to blast overpressure by N-acetylcysteine amide. Shock 2009;32:325–31. 29. Lavery GG, Lowry KG. Management of blast injuries and shock lung. Curr Opin Anaesthesiol 2004;17:151–7. 30. Pizov R, Oppenheim-Eden A, Matot I, Weiss YG, Eidelman LA, Rivkind AI, et al. Blast lung injury from an explosion on a civilian bus. Chest 1999;115:165–72. 31. Karapolat S, Gezer S, Aydin LY, Dumlu T, Kandis H. Management of traumatic pneumothorax. Hong Kong Med J 2010;16:413.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Bir tavşan modelinde blast travmasıyla indüktlenen pulmoner mikrovasküler disfonksiyon ve patolojik değişiklikler Dr. Si-Yu Wu,1 Dr. Geng-Fen Han,1 Dr. Jian-Yi Kang,2 Dr. Liang-Chao Zhang,2 Dr. Ai-Min Wang,1 Dr. Jian-Min Wang2,3 Üçüncü Askeri Tıp Üniversitesi, Daping Hastanesi, Ortopedi Bölümü, Chongqing, 400042, PR Çin Üçüncü Askeri Tıp Üniversitesi, Daping Hastanesi ve Alan Cerrahisi 6. Araştırma Enstitüsü Departmanı,, Chongqing, 400042, PR Çin 3 Üçüncü Askeri Tıp Üniversitesi, Key Devlet Travma, Yanık ve Kombine Yaralanmalar Laboratuvarı, Chongqing, 400042, PR Çin 1 2

AMAÇ: Eksplosif pulmoner barotravmada vasküler kaçağın kritik bir rol oynadığı kanıtlanmıştır. Bu çalışmada vasküler kaçağın bir giderek artan şiddet derecesindeki blast travması serisinde şiddet derecesiyle pulmoner vasküler kaçağa ilişkili altyapısal kanıtlar kantitatif olarak araştırıldı. GEREÇ VE YÖNTEM: Yüz adet erkek beyaz Yeni Zelanda tavşan detonatörden uzaklıklarına göre beş gruba randomize edildi (10 cm, 15 cm, 20 cm, 30 cm ve plasebo kontrol). Pulmoner vasküler kaçağın miktarı radyoaktif 1251-albümin etiketleme yöntemiyle izlendi. Blast dalgasının neden olduğu patolojik değişiklikler ışık ve elektron mikroskobuyla incelendi. BULGULAR: 125I-albüminin kapillerlerden kaçış hızı ve her iki akciğerde rezidüel radyoaktivite detonatörden 10, 15 ve 20 cm mesafede anlamlı derecede artmış olması bu gruplarda şiddetli derecede vasküler kaçağın olduğunu düşündürmektedir. Ultrastrüktürel gözlem 10 ve 15 cm’lik gruplarda akciğer kapillerlerinde ödem ve endotel hücreleri arasındaki mesafenin açıldığını gösterdi. TARTIŞMA: Primer blast dalgası akciğer kapillerlerinden kan sızıntısına neden olabilmektedir. Blast dalgası akciğer kapillerlerinin endotel hücrelerinin şişmesine neden olabilmekte, endotel hücrelerinin arasındaki mesafenin artması pulmoner vasküler kaçaktan sorumlu olabilmektedir. Anahtar sözcükler: Blast travması; permeabilite; pulmoner disfonksiyon; vasküler kaçak. Ulus Travma Acil Cerrahi Derg 2016;22(5):405–411

doi: 10.5505/tjtes.2015.06005

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A new experimental burn model with an infrared heater Serbülent Güzey, M.D.,1 Ahmet Demirhan Dal, M.D.,2 İsmail Şahin, M.D.,3 Mustafa Nişancı, M.D.,4 İbrahim Yavan, M.D.5 1

Department of Plastic Reconstructive and Aesthetic Surgery, Kasımpaşa Military Hospital, İstanbul-Turkey

2

Department of Plastic Reconstructive and Aesthetic Surgery, Erzurum Military Hospital, Erzurum-Turkey

3

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

4

Department of Plastic Reconstructive and Aesthetic Surgery, Medical Park Hospital, İstanbul-Turkey

5

Department of Pathology, Gülhane Military Medical Academy, Ankara-Turkey

ABSTRACT BACKGROUND: This study was undertaken to develop new experimental burn injury model using conventional infrared heaters. METHODS: 21 Sprague-Dawley rats were divided into 3 groups. Portion of dorsal area was exposed to infrared radiation from distance of 50 cm to create burn injury. Length of exposure to heat for Group 1 was 5 minutes; Group 2 was exposed for 7½ minutes, and Group 3 was exposed for 10 minutes. Macroscopic and histopathological evaluations were utilized to demonstrate depth and characteristics of injury. RESULTS: There was no burn injury in first group. Group 2 developed partial thickness burn, and result was full thickness burn injury in Group 3. In Groups 2 and 3 there was statistically significant difference in dermal collagen denaturation. Dermal injury depth was statistically significantly higher in Group 3 compared to Group 2. CONCLUSION: New experimental burn injury model is described using conventional infrared heaters. Standard variables pertaining to model were defined to produce burn injuries at predictable depth: 10 minutes of exposure from 50 cm distance for full thickness burn, and 7½ minutes of exposure from the same distance for partial thickness injury. Keywords: Burn; infrared heater; rat model.

INTRODUCTION

still very important for research purposes.

Though a better understanding of burn trauma has improved survival of burn patients in recent years, there are still many points to be researched that may lead to discovery of new treatment modalities.[1–3] Rat experimental models are mostpreferred option, and various models (e.g., scalding, direct contact with heated metal, or application of electrical current or chemical agent) have been used since the 1960s.[2,4–6] However, all of these models have disadvantageous, such as optimization. Therefore, defining a reliable experimental model is

Infrared heaters are popular, commonly available devices that transfer heat to another object through electromagnetic radiation without increasing nearby air temperature. Infrared spectrum is wavelength from 0.7 to 300 μm.[7] Heat energy is released when molecules in object with lower temperature become excited and vibrate upon contact with infrared wave. Absorption of heat released as result of exothermic reaction can be sufficient to cause burn trauma.[8,9]

Address for correspondence: Serbülent Güzey, M.D. Kasımpaşa Asker Hastanesi, Plastik Rekonstrüktif ve Estetik Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 264 04 37 E-mail: drserbulent@yahoo.com Qucik Response Code

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The present study researched a new, practical, and standardized rat burn model using infrared heaters based on previously reported papers.[10,11] Primary target for 8.25 μm radiation emitted by heater is dermal collagen.

MATERIALS AND METHODS Approval for the study was obtained from Gülhane Military Medicine Academy animal research ethics committee. In order to achieve uniform burn areas, protective shied with 4x5 cm aperture in the middle was prepared and covered Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


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with aluminum foil to reflect heat and protect adjacent tissue. A standard, popular, and easily available model of infrared heater was selected: 220–230 v, 50-60 Hz, 2300–2500 watt heating unit with dimensions of 86x19x10 cm (UFO-L23; UFO Heating Systems, Istanbul, Turkey). Distance between heater and rat, and length of time exposed to heat were the variables were taken into consideration to determine experimental model. A preliminary study was conducted to identify optimal distance. First rat was placed 25 cm from heater and after 5 minutes, third-degree burn injury appeared. No damage occurred at distance of 1 m, which was the minimum safe distance according to manufacturer’s instruction manual, even after 30 minutes. Air temperature of area behind protective shied was measured, as it could affect burn depth at measurement over 40°C. After 5 minutes at a distance of 25 cm, surrounding area temperature was 43°C and 42.5°C at 40 cm. However, at a distance of 50 cm, it was below 40°C even after 10 minutes and observance of full thickness burn injury. Therefore, 50 cm was selected as optimal distance between heater and rats for model (Fig. 1). 21 Sprague-Dawley rats weighing between 250 and 275g were randomly divided into 3 groups of 7. Anesthesia was performed with combination 5 mg/kg ketamine, 2 mg/kg xylazine administered intraperitoneally. Following anesthesia, dorsal skin location was shaved as target area. Protective shield was positioned parallel to heater. In the first group, rats were exposed to heat from 50 cm distance for 5 minutes; second and third groups were placed at same distance for 7½ and 10 minutes, respectively (Table 1, Fig. 2).

Assessment Methods Skin elasticity, turgor, and tonus were evaluated in all specimens by single researcher in macroscopic evaluation. Table 1. Experiment protocol Group

Distance Time Number of rats (cm) (min) (n)

Group 1

50

5

7

Group 2

50

7

Group 3

50

10

7

Figure 1. The setup of burn model.

Figure 2. Group 1 (right), Group 2 (middle), and Group 3 (left) rats after thermal injury.

Rats were euthanized following macroscopic assessment with large dose of anesthetic. Full thickness tissue samples were collected, as well as 1 cm healthy tissue sample for comparison, taken from area adjacent to burn. Biopsy materials were stained with hematoxylin and eosin (H&E) and evaluated under 20x amplification light microscope by single-blind pathologist. Dermal collagen denaturation, dermal injury depth and injuries to skin appendices were evaluated semi-quantitatively using scoring system (Table 2). Data obtained from histopathological evaluation were evaluated statistically using chi-square test; p<0.05 was considered significant.

Table 2. Histological scoring system Dermal collagen denaturation None Mild Moderate

Dermal injury depth

Skin appendices injury

Histological score

None

None

0

Partial thickness

Exist

1

Full thickness

2

Severe

3

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RESULTS

Table 3. Macroscopic and histological pictures of all groups

Macroscopic assessment revealed decreased skin elasticity and reduced turgor pressure and tonus in Group 3 (Fig. 3, 4).

Group 1 (50 cm 5 min)

Histological examination indicated homogeneous burn injury in all parts of burn area. Although some inflammatory changes in adjacent healthy tissue were detected, they were not severe and burn margins were clear.

No injury

Only subepithelial neutrophils and edema formation were observed in first group. Mean histological score was zero for criteria of dermal collagen denaturation, dermal injury depth, and skin appendices injuries. In second group, exposed to heat for a longer period, denatured collagen bundles were seen, but limited to upper half of dermis. Although epidermal change (edema) was present in this group, there was no injury to skin appendices. Histological scores of second group were 1, 1, and 0, respectively, for the 3 criteria evaluated. In third group, denatured collagen bands were observed throughout dermis layer, as well as epithelial changes, degenerated skin extensions, and muscle edema. Groupâ&#x20AC;&#x2122;s mean histological scores were 2, 2, and 1. Histological differences indicated full thickness burn injury in Group 3 and partial thickness burn in Group 2 (Table 3).

Group 2 (50 cm 71/2 min)

Group 3 (50 cm 10 min)

Partial thickness injury

Full thickness injury

Statistically significant difference in dermal collagen denaturation (p<0.05) was found in the second and third groups compared to first group. Statistically significant difference (p<0.05) in dermal injury depth was detected between second and third groups. Skin appendices assessment revealed no injury in first 2 groups, and finding was statistically significant (p<0.05). These results confirmed full thickness burn injury in Group 3 and partial thickness burn injury in Group 2.

DISCUSSION Although burn injuries are now better understood, additional research is still needed. To study burn physiopathology and to test treatment options, various experimental burn models have been developed and used, such as scalding, direct contact with heated metal, and application of electrical current or chemical agent.

Figure 3. Turgor pressure and skin tonus of a subject in Group 1.

The present study used a conventional infrared heater to formulate a new experimental burn model. This model is extremely easy to implement, repeatable, and yields burn injuries of consistent depth. Uniform partial thickness or full thickness burn injuries can be induced using this method. Ideal experimental model has features such as low cost and safety for the researcher; however, the most important characteristic is standardization and replicability. Among disadvantages of burn models using heated metal plates or similar devices is difficulty of maintaining uniform pressure and precise positioning of instrument. In addition, laboratory accidents that can injure the researcher may occur with heated metal and water-related burn models.

Figure 4. Turgor pressure and skin tonus of a subject in Group 3.

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be manipulated while inducing burn. Thus, method is extremely safe way for researchers to achieve standardized burn depth compared to other methods using boiling water and contact burns. Though it does require more time to perform burn, the present model is also less traumatic for researcher. Use of infrared heater also provides flexibility. In the present study, with 4x5 cm opening in the shield, a burn area of less then 20% of total body surface area (BSA) was created. No resuscitation was required. Change in size of opening would allow researchers to create conditions for study of numerous topics related to burn trauma, such as burn physiopathology in different burn percentages, varied treatment modalities, early treatment, or resuscitation. In experimental studies, various animals are used as test subjects.[12–22] When defining present model, rats were selected because they are easily acquired, inexpensive, and easy to manipulate compared to larger animals. Due to need for only conventional infrared heater and rats, model offers genuinely low cost alternative for burn studies. During the study process it was observed that epidermal structures are affected only after longer periods of exposure to heat source and primary target of infrared radiation is dermal collagen. Therefore, it is foreseen that infection would be rare with this model as epidermal layer would be partially healthy. Further studies are recommended based on these initial findings. Even among experienced researchers, correct burn depth estimation ranges between 64 and 76%. Optimal method for estimation of burn depth is histological evaluation. H&E staining has been used to determine partial and full thickness burns, normal and denatured collagen fibers, and patent vascular structure for many years.[23] In present study, biopsy samples were embedded in paraffin blocks, samples 5 μm thick were taken, stained with H&E, and assessed by single pathologist in order to objectively determine ideal length of exposure to heat and distance between subject and device to achieve standardized burn injury.

Conclusion In this study, a new experimental burn model using a conventional infrared heater is described. Full thickness burn was achieved by positioning rats 50 cm from infrared heater for 10 minutes, and partial thickness burn damage resulted after 7½ minutes at same distance. Histopathological changes resulting from infrared heater burn injury are described. Model is practical, replicable, yet flexible method for burn injury research. Conflict of interest: None declared.

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REFERENCES 1. Santos Heredero FX, Hamann C, Obispo Martin JM, Rodriguez Arias C, Coca Menchero S. Experimental Burn Models. Ann Burns Fire Disasters 1996:2;96–101. 2. Yang E, Maguire T, Yarmush ML, Berthiaume F, Androulakis IP. Bioinformatics analysis of the early inflammatory response in a rat thermal injury model. BMC Bioinformatics 2007;8:10. 3. Kataranovski M, Magić Z, Pejnović N. Early inflammatory cytokine and acute phase protein response under the stress of thermal injury in rats. Physiol Res 1999;48:473–82. 4. Meyer TN, da Silva AL. A Standard Burn Model Using Rats. Acta Cir Bras 1999. 5. Stevens EJ, Ryan CM, Friedberg JS, Barnhill RL, Yarmush ML, Tompkins RG. A quantitative model of invasive Pseudomonas infection in burn injury. J Burn Care Rehabil 1994;15:232–5. 6. Asko-Seljavaara S. Burn research--animal experiments. Acta Physiol Scand Suppl 1986;554:209–13. 7. Liew SC. “Electromagnetic waves”. Centre for Remote Imaging, Sensing and Processing. http://www.crisp.nus.edu.sg/~research/tutorial/ em.htm. 8. Kameyama K. Histological and clinical studies on the effects of low to medium level infrared light therapy on human and mouse skin. J Drugs Dermatol 2008;7:230–5. 9. Siegel R, Howell JR. Thermal radiation heat transfer. 4th ed. Bedford RH (ed). New York: Taylor & Francis; 2002. 10. Surrell JA, Alexander RC, Cohle SD, Lovell FR Jr, Wehrenberg RA. Effects of microwave radiation on living tissues. J Trauma 1987;27:935–9. 11. Gurfinkel R, Singer AJ, Cagnano E, Rosenberg L. Development of a novel animal burn model using radiant heat in rats and swine. Acad Emerg Med 2010;17:514–20. 12. Knabl JS, Bayer GS, Bauer WA, Schwendenwein I, Dado PF, Kucher C, et al. Controlled partial skin thickness burns: an animal model for studies of burnwound progression. Burns 1999;25:229–35. 13. Brans TA, Dutrieux RP, Hoekstra MJ, Kreis RW, du Pont JS. Histopathological evaluation of scalds and contact burns in the pig model. Burns 1994;20 Suppl 1:48–51. 14. Nanney LB, Wenczak BA, Lynch JB. Progressive burn injury documented with vimentin immunostaining. J Burn Care Rehabil 1996;17:191–8. 15. Converse JM, Platt JM, Ballantyne DL Jr. An experimental evaluation of a histochemical diagnosis of burn depth. J Surg Res 1965;5:547–51. 16. Zawacki BE. Reversal of capillary stasis and prevention of necrosis in burns. Ann Surg 1974;180:98–102. 17. deCamara DL, Raine TJ, London MD, Robson MC, Heggers JP. Progression of thermal injury: a morphologic study. Plast Reconstr Surg 1982;69:491–9. 18. Chvapil M, Speer DP, Owen JA, Chvapil TA. Identification of the depth of burn injury by collagen stainability. Plast Reconstr Surg 1984;73:438–41. 19. Kaufman T, Lusthaus SN, Sagher U, Wexler MR. Deep partial skin thick ness burns: a reproducible animal model to study burn wound healing. Burns 1990;16:13–6. 20. Cribbs RK, Luquette MH, Besner GE. A standardized model of partial thickness scald burns in mice. J Surg Res 1998;80:69–74. 21. Singer AJ, Berruti L, Thode HC Jr, McClain SA. Standardized burn model using a multiparametric histologic analysis of burn depth. Acad Emerg Med 2000;7:1–6. 22. Papp A, Kiraly K, Härmä M, Lahtinen T, Uusaro A, Alhava E. The progression of burn depth in experimental burns: a histological and methodological study. Burns 2004;30:684–90. 23. Jaskille AD, Shupp JW, Jordan MH, Jeng JC. Critical review of burn depth assessment techniques: Part I. Historical review. J Burn Care Res 2009;30:937–47.

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İnfrared ısıtıcı kullanarak oluşturulan yeni bir deneysel yanık modeli Dr. Serbülent Güzey,1 Dr. Ahmet Demirhan Dal,2 Dr. İsmail Şahin,3 Dr. Mustafa Nişancı,4 Dr. İbrahim Yavan5 Kasımpaşa Asker Hastanesi, Plastik Rekonstrüktif ve Estetik Cerrahi Kliniği, İstanbul Erzurum Asker Hastanesi, Plastik Rekonstrüktif ve Estetik Cerrahi Kliniği, Erzurum Koru Hastanesi, Plastik Rekonstrüktif ve Estetik Cerrahi Kliniği, Ankara 4 Medical Park Hastanesi, Plastik Rekonstrüktif ve Estetik Cerrahi Kliniği, İstanbul 5 Gülhane Askeri Tıp Akademisi, Patoloji Anabilim Dalı, Ankara 1 2 3

AMAÇ: Bu çalışma konvansiyonel infrared ısıtıcılar kullanılarak yeni bir yanık modeli tanımlanması amacıyla gerçekleştirildi. GEREÇ VE YÖNTEM: Yirmi bir adet Sprague-Dawley sıçan üç gruba ayrıldı. Sıçanların sırt derisi zaman ve mesafe değişkenleri doğrultusunda; 50 cm 5 dakika (Grup 1), 50 cm 7.5 dakika (Grup 2) ve 50 cm 10 dakika (Grup 3) olacak şekilde infrared ısıtıcıya maruz bırakıldı. Yanığın derecesi ve karakterinin belirlenmesi amacıyla makroskobik ve histopatolojik değerlendirme yapıldı. BULGULAR: Birinci grupta yanık oluşumu izlenmezken, ikinci grupta parsiyel kalınlıkta, üçüncü grupta ise tam kat yanık oluşumu izlendi. İki ve üçüncü gruplar arasında dermal kollajen denatürasonu açısından istatistiksel olarak anlamlı farklılıklar gözlemlendi. Dermal hasarlanma üçüncü grupta ikinci gruba kıyasla daha derin olduğu gözlemlendi. TARTIŞMA: Konvansiyonel infrared ısıtıcılar kullanılarak yeni bir yanık modeli tanımlanırken model içerisinde standart değişkenlerde ortaya koyuldu. Buna göre 50 cm mesafeden 10 dakika infrared ısıtıcıya maruz kalınmasıyla tam kat, aynı mesafeden 7.5 dakika maruz kalınmasıyla kısmi kalınlıkta yanık modelleri oluşturuldu. Anahtar sözcükler: İnfrared ısıtıcı; sıçan modeli; yanık. Ulus Travma Acil Cerrahi Derg 2016;22(5):412–416

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doi: 10.5505/tjtes.2015.93464

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Protective effect of betaine against burn-induced pulmonary injury in rats Ahmet Özer Şehirli, M.D.,1,2 Burcu Satılmış, M.D.,3 Şermin Tetik, M.D.,4 Şule Çetinel, M.D.,5 Berrak Yeğen, M.D.,6 Aslı Aykaç, M.D.,7 Göksel Şener, M.D.1 1

Department of Pharmacology, Marmara University Faculty of Pharmacy, İstanbul-Turkey

2

Near East University, Faculty of Dentistry, Lefkoşa-KKTC

3

Department of Pharmacy, Acıbadem Maslak Hospital, İstanbul-Turkey

4

Department of Biochemistry, Marmara University Faculty of Pharmacy, İstanbul-Turkey

5

Department of Histology-Embryology, Marmara University Faculty of Medicine, İstanbul-Turkey

6

Department of Physiology, Marmara University Faculty of Medicine, İstanbul-Turkey

7

Department of Biophysics, Near East University Faculty of Medicine, Lefkoşa-KKTC

ABSTRACT BACKGROUND: This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. METHODS: Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90°C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25°C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis. RESULTS: Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. CONCLUSION: Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue. Keywords: Betaine; cytokines; lung injury; oxidative stress; thermal trauma.

INTRODUCTION Thermal trauma is one of the most common problems faced in the emergency room. It may cause multiple organ injury distant from the burned area; therefore, morbidity and mortality is increased in thermal trauma patients.[1] In addition to direct tissue damage, inflammatory reactions and infection as major complications.[2] Address for correspondence: Ahmet Özer Şehirli, M.D. Tıbbiye Caddesi, No: 49, Haydarpaşa, İstanbul, Turkey Tel: +90 532 - 520 56 74 E-mail: ozersehirli@hotmail.com Qucik Response Code

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In thermal trauma patients, the lungs are the most affected organs as a result of the inflammatory process since the lungs produce inflammatory mediators and free oxygen radicals.[3] Several substances, including free oxygen radicals, vasodilators, and chemical mediators, activate pneumocytes. These substances pass through systemic blood and increase the inflammatory response, which causes edema, surfactant alterations, bronchial obstruction, and hypoxia, as well as development of systemic inflammatory response syndrome (SIRS) in patients with burns.[3,4] Betaine is a natural chemical compound found in several foods such as wheat, shellfish, spinach, and sugar beets.[5] The first effect of betaine molecule, as an osmolyte, is to protect cells, proteins, and enzymes under osmotic stress conditions, drought, high salinity, or high temperature. Betaine also acts as a methyl donor in many biological pathways.[6] It has been demonstrated in studies that betaine prevented membrane 417


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stabilization in tissue by restoring both non-enzymatic and enzymatic antioxidants, and that it had a protective effect on mitochondrial function, lipid metabolism, and antioxidant defense system in experimentally induced myocardial infarction in Wistar rats.[7–11]

In order to evaluate presence of oxidant injury in the organ (lung), tissue samples were taken and stored at -80°C in order to determine malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) and Na+/K+ATPase activity.

Neutrophil infiltration is known as the source of free oxygen radicals causing afterburn injury, as well as being responsible for local and distant injury.[12] Various mediators and cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β), play important roles in major complications of burn injury. Betaine also modulates immune functions of liver macrophages under osmotic stress through TNF-α release, phagocytosis, depression of prostaglandin synthesis, and cyclooxygenase-2 (COX-2) expression.[13]

Tissue samples were fixed in 10% (v/v) buffered p-formaldehyde and prepared for routine parafin embedding for histological analysis. Tissue sections (6 μm) were stained with hematoxylin and eosin (H&E) and examined under a light microscope (Olympus-BH-2; Olympus Corporation, Tokyo, Japan). An expert histologist who was unaware of the treatment group properties performed histological assessments.

In light of these findings, the present study was designed to investigate whether and to what extent betaine would provide protection against burn-induced tissue damage by determining the presence of oxidative tissue injury using biochemical and histological parameters.

MATERIALS AND METHODS Animals Wistar albino rats of both sexes weighing 200 to 250 g were obtained from Marmara University School of Medicine Animal Facility. The rats were kept at a constant temperature (22±1ºC) with 50% humidity, 12-hour light and dark cycles, and fed with standard rat chow until 12 hours before the experiment without restriction of access to water. All experimental protocols were approved by the Marmara University Animal Care and Use Committee (33.2010.mar).

Thermal Injury and Experimental Design Rats were divided into 3 groups: control, burn, and betainetreated burn group. Each group consisted of 6 rats. For a second-degree burn involving 30% of total body surface area, dorsum of rats was shaved and subsequently exposed to 90°C water bath for 10 seconds while under brief ether anesthesia. [14] This second-degree burn method was chosen to investigate the effects of betaine on partial-thickness burn damage. Animals were then resuscitated with 10 mL/kg subcutaneous infusion of physiological saline solution to hind limb. Betaine (Lily’s) was administered orally (250 mg/kg) for a period of 21 days before thermal injury and single dose of betaine was administered after burn. In both saline- and betaine-treated burn groups, rats were decapitated at 24 hours following burn injury. In order to rule out the effects of anesthesia, same protocol was used with control group, except that dorsum was dipped in 25°C water bath for 10 seconds. After decapitation, blood was collected to assay pro-inflammatory cytokines (TNF-α and IL-1β) and lactate dehydrogenase (LDH) activity. 418

Cytokine Assay TNF-α and IL-1β were analyzed based on manufacturer’s instructions and guidelines using enzyme-linked immunosorbent assay (ELISA) kits (Biosource International, Nivelles, Belgium) specifically for plasma levels of rat cytokines. These kits were selected based on high degree of sensitivity and specificity, interassay and intraassay precision, and small amount of plasma sample required to conduct assay. Serum LDH levels were determined spectrophotometrically using an automated analyzer.[15]

Malondialdehyde and Glutathione Assays To determine MDA and GSH levels, samples of tissue were homogenized with ice-cold 150 mM KCl. As described by Beuge et al.,[16] MDA levels were assayed by monitoring formation of thiobarbituric acid reactive substances (TBARS), products of lipid peroxidation. Lipid peroxidation was expressed in terms of MDA equivalents using an extinction coefficient of 1.56 x 105 M–1 cm–1 and results are expressed as nmol MDA/g tissue. GSH measurements were performed with modification of Ellman procedure.[17] After centrifugation at 1077 × g for 10 min, 0.5 mL supernatant was added to 2 mL of 0.3 mol/L Na2HPO4.2H2O solution. A 0.2 mL solution of dithiobisnitrobenzoate (0.4 mg/mL 1% sodium citrate) was added and absorbance at 412 nm was measured immediately after mixing. GSH levels were calculated using an extinction coefficient of 1.36 x 104 M–1 cm.–1 Results are expressed in µmol GSH/g tissue.

Myeloperoxidase Activity MPO is an enzyme found predominantly in the azurophilic granules of polymorphonuclear neutrophils (PMN). Tissue MPO activity is frequently utilized to estimate tissue PMN accumulation in inflamed tissue and correlates significantly with the number of PMN histochemically determined in tissue. MPO activity was measured in tissue using procedure similar to that documented by Hillegass.[18] Tissue samples were homogenized in 50 mM potassium phosphate buffer (PB, pH 6.0), and centrifuged at 41400 × g (10 min); pellets were suspended in 50 mM PB containing 0.5% hexadecyltrimethylamUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


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monium bromide (HETAB). After 3 freeze and melt cycles, with sonication between cycles, samples were centrifuged at 41400 × g for 10 min. Aliquots (0.3 mL) were added to 2.3 mL of reaction mixture containing 50 mM PB, o-dianisidine and 20 mM H2O2 solution. One unit of enzyme activity was defined as amount of MPO present that caused change in absorbance measured at 460 nm for 3 minutes. MPO activity is expressed as U/g tissue.

Statistical Analysis Statistical analysis was carried out using GraphPad software (Prism 3.0; GraphPad Software, San Diego, CA, USA). All data were expressed as means±SEM. Groups of data were compared with analysis of variance (ANOVA) followed by Tukey’s multiple comparison tests. Values of p<0.05 were regarded as significant.

RESULTS

Na+/K+-ATPase Activity Since activity of Na+/K+-ATPase, a membrane-bound enzyme required for cellular transport, is very sensitive to free radical reactions and lipid peroxidation, reductions in activity can indicate membrane damage indirectly. Measurement of Na+/ K+-ATPase activity is based on measurement of inorganic phosphate released by ATP hydrolysis during incubation of homogenates with an appropriate medium containing 3 mM ATP as substrate. Total ATPase activity was determined in presence of 100 mM NaCl, 5 mM KCl, 6 mM MgCl2, 0.1 mM ethylenediaminetetraacetic acid (EDTA), 30 mM Tris HCl (pH 7.4), while Mg2+-ATPase activity was determined in the presence of 1mM ouabain. Difference between total and Mg2+-ATPase activities was taken as a measure of Na+/K+-ATPase activity.[19] Reaction was initiated with addition of homogenate (0.1 mL), and 5-minute pre-incubation period at 37º C was allowed. Following addition of Na2ATP and a 10-minute re-incubation period, reaction was terminated with addition of ice-cold 6% perchloric acid. Mixture was then centrifuged at 3500 g, and Pi in the supernatant fraction was determined with Fiske and Subbarow method.[20] Specific activity of enzyme was expressed as nmol Pi mg–1 protein h–1. Protein concentration of supernatant was measured with Lowry method.[21]

As shown in Table 1, Serum LDH activity and plasma levels of pro-inflammatory cytokines (TNF-α, IL-1β) in burn group were significantly higher (p<0.001) than those of control group, and betaine treatment significantly reduced the elevations (p<0.001). In accordance with these findings, level of the major cellular antioxidant GSH in vehicle-treated burn group was depleted (p<0.001); however, in betaine-treated burn group, depleted GSH stores were partially replenished with this antioxidant (p<0.05; Fig. 1a). MDA level, measured as major degradation product of lipid peroxidation in lung tissue, was found to be significantly higher in burn group (p<0.01) compared to that of control group, while treatment with betaine reduced elevation (p<0.05; Fig. 1b).

Histopathological Analysis

MPO activity, accepted as an indicator of neutrophil infiltration, was significantly higher in lung tissue of burn group treated with vehicle (p<0.01) than that of control group (Fig. 2a). Activity of Na+/K+-ATPase, indicating functional transport capacity of lung cells, was found to be significantly decreased in burn group compared to control group (p<0.001); however, betaine treatment significantly reduced burn-induced decrease in lung Na+/K+-ATPase activity (p<0.05; Fig. 2b).

For light microscopic investigations, lung specimens were fixed in 10% buffered formalin for 48 hours, dehydrated in ascending alcohol series, and embedded in paraffin wax. Approximately 5-μm-thick sections were stained with H&E for general morphology. Histological assessments were made with a photomicroscope (Olympus BX 51; Olympus Corporation, Tokyo, Japan) by an experienced histologist who was unaware of experimental groups and each group was described in detail.

In control group, alveolar structure and interstitial space were found to be regular (Fig. 3a). In burn group, severe inflammation, congestion, and alveolar volume decrease due to edema of interstitial space were found in burned lung tissue, and erythrocytes were observed inside alveoli and part of alveolar wall (Fig. 3b). In the betaine-treated burn group, regression of inflammation and congestion were found, as well as decrease in interstitial edema (Fig. 3c).

Table 1. Serum lactate dehydrogenase (LDH) activity (U/I), tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) levels of control, vehicle-treated, and betaine-treated burn groups. For each group, n=6

Control Burn Burn-Betaine 2373±165*** 1480±109+++

Lactate dehydrogenase

1383±134

TNF-α

8.12±1.03 43.06±5.12*** 15.08±2.08+++

IL-1β

16.22±1.52 68.28±4.08*** 33.25±6.98+++

p<0.001, compared to control group; +++p<0.01, compared to betaine-treated burn group.

***

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(a)

(a)

2.5

+ 1.5

***

1.0

(b)

+

20

10

0.5 0.0

**

30 MPO (U/g)

GSH (μmol/g)

2.0

40

Control

Burn

0

Burn-Betaine

(b)

80

Control

Burn

Burn-Betaine

3

MDA (nmol/g)

+ 40

20

Control

Burn

Na+ - K+ ATPase

** 60

Burn-Betaine

+

2

*** 1

Control

Burn

Burn-Betaine

Figure 1. (a) Glutathione (GSH), (b) malondialdehyde (MDA) level in lung tissue of control, vehicle-treated burn, and betainetreated burn groups. Each group consisted of 6 animals. **p<0.01; *** p<0.001, compared to control group; +p<0.05, compared to vehicle-treated burn group.

Figure 2. (a) Myeloperoxidase (MPO), (b) Na+/K+-ATPase activity in lung tissue of control, vehicle-treated burn, and betainetreated burn groups. Each group consisted of 6 animals. **p<0.01; *** p<0.001, compared to control group; +p<0.05, compared to vehicle-treated burn group.

DISCUSSION

fense system in experimentally induced myocardial infarction in Wistar rats.[7–11]

Burns generated in the present study led to significant increases in lipid peroxidation and MPO activity, along with decreased GSH level and Na+/K+-ATPase activity in lung tissue, and elevated serum level of LDH and pro-inflammatory mediators TNF-α, and IL-1β, demonstrating presence of systemic oxidative injury due to thermal injury. Betaine administration protected against systemic oxidative injury and limited tissue damage. Studies have shown that betaine prevents membrane stabilization in tissue by restoring both non-enzymatic and enzymatic antioxidants, and that it has a protective effect on mitochondrial function, lipid metabolism, and antioxidant de-

(a)

Thermal injury model is most preferred experimental study method with regard to burns. Distant organ injury caused by burns is a clinical situation triggered by inflammatory reaction. After thermal trauma, there is a complex relationship between tissue types and several immunoregulator systems such as arachidonic acid/prostaglandin pathway, complement pathways, cytokine network, neuroendocrine, and metabolic regulatory system.[22,23] Release of pro-inflammatory mediators such as IL-1β, IL-6, and TNF-α is factor in immune dysfunction. In the present study, it was observed that TNF-α and IL-1β levels were significantly elevated after burn injury.

(b)

(c)

➵ Figure 3. (a) The control group: (**) regular alveolar structure and interstitial space, (→) alveolary epitelium. (b) The burn group: (→) severe inflammation, congestion, and (*) alveolar volume decrease (➵) erythrocytes inside alveoli. (c) The betaine treated burn group: (**) regression of inflammation and congestion, (→) mild interstitial edema. (HE x200; insets x400).

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In betaine-treated burn injury group, levels of cytokines were suppressed, indicating that betaine has an important role in pro-inflammatory cytokine levels in blood. Therefore, agents such as betaine could be helpful in preventing tissue oxidation and could improve success of burn treatment. Other studies have also determined that betaine has an inhibitory effect on cytokines.[26,27] [24,25]

Another indicator for tissue injury is alteration of LDH level. [28] In their study, Wettstein and Häussinger showed that betaine decreased LDH level on perfused rat liver after ischemia and reperfusion through its cytoprotective effect.[29] In the present study, LDH level of rats with thermal injury was found to be high; however, in betaine-treated group it was significantly lower. Study results have indicated that increased MDA level is related to oxidative injury caused by thermal trauma.[30] Kanbak et al. reported that betaine has cytoprotective effect, decreasing MDA level and countering cytotoxic effect of free radicals caused by chronic ethanol administration to pancreas tissues.[31]

ment group. In one study, antioxidant effect of betaine was examined in rats given gastric defect as result of consuming HCl-ethanol. Betaine reduced free radicals, DNA, lipid, and protein damage caused by HCl-ethanol. Oral betaine administration preserved structure and function of membrane, and had protective effect against lipid peroxidation and protein carbonyl function caused by reactive oxidants.[33] These findings suggest that betaine inhibits free radicals and lipid peroxidation, and therefore Na+/K+-ATPase activity is decreased. This experimental thermal burn model led to increase in pro-inflammatory blood cytokines, decrease in antioxidant balance caused by neutrophil activation, increase in free radical levels, and tissue injury because of the lipid peroxidation. These results caused tissue injury not only in the burn area, but also in distant organs. Findings indicate that betaine possesses neutrophil-dependent, anti-inflammatory effect that prevents burn-induced damage in tissue and protects against oxidative organ damage. Use of betaine could be helpful to improve quality of life and recovery of patients with burn-induced lung injury.

In the current study, MDA level in lung tissue increased. This increase was related to lipid peroxidation, which correlates with previous studies and supports role of free radicals in burn-induced injury.[32] In betaine-treated group, increased MDA level caused by injury was significantly decreased.

Acknowledgement

GSH protects cell against oxidative injury by reacting with free radicals and peroxidate.[28] In the present study, lung tissue structure was damaged by burn due to oxidative stress. Other studies have also shown that GSH level in lung tissue significantly decreased with betaine treatment after burn,[22,28,33] as was the case in current study. Antioxidant therapy is now used in several pathological conditions with oxidant stress, and results have been positive.[28] Kim and Kim showed that for hepatotoxicity caused by chloroform, betaine increased plasma and liver glutathione levels through its effect on transsulfuration pathway in liver.[34] In the present study, betaine applied after burn helped significantly reduce GSH level in lung tissue.

Conflict of interest: None declared.

Neutrophils are responsible for tissue injury distant from burn area, and activated neutrophils release MPO enzyme. Betaine inhibits neutrophil infiltration and prevents tissue injury due to MPO activity.[12] Present study data indicated that MPO activity in lung tissue elevated by burn decreased with betaine treatment. Na+/K+-ATPase is membrane-bound enzyme responsible for active transport of several ions in the cell membrane. Local or systemic tissue Na+/K+-ATPase activity is inhibited in case of thermal injury by effect of free radicals.[22] As seen in the literature, in present study, Na+/K+-ATPase activity significantly decreased in burn group and increased in treatUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

This research was supported by Marmara University scientific research committee under project number SAGB-150513-0147.

REFERENCES 1. Cakir B, Cevik H, Contuk G, Ercan F, Ekşioğlu-Demiralp E, Yeğen BC. Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats. Regul Pept 2005;125:135–44. 2. Ramallo BT, Lourenço E, Cruz RH, Almeida JC, Taha MO, Silva PY, et al. A comparative study of pentoxifylline effects in adult and aged rats submitted to lung dysfunction by thermal injury. Acta Cir Bras 2013;28:154–9. 3. Herndon DN, Traber DL. Pulmonary circulation and burns and trauma. J Trauma 1990;30(12 Suppl):41–4. 4. Craig SA. Betaine in human nutrition. Am J Clin Nutr 2004;80:539–49. 5. Amiraslani B, Sabouni F, Abbasi S, Nazem H, Sabet M. Recognition of betaine as an inhibitor of lipopolysaccharide-induced nitric oxide production in activated microglial cells. Iran Biomed J 2012;16:84–9. 6. Kharbanda KK, Rogers DD 2nd, Mailliard ME, Siford GL, Barak AJ, Beckenhauer HC, et al. A comparison of the effects of betaine and S-adenosylmethionine on ethanol-induced changes in methionine metabolism and steatosis in rat hepatocytes. J Nutr 2005;135:519–24. 7. Balkan J, Parldar FH, Doğru-Abbasoğlu S, Aykaç-Toker G, Uysal M. The effect of taurine or betaine pretreatment on hepatotoxicity and prooxidant status induced by lipopolysaccharide treatment in the liver of rats. Eur J Gastroenterol Hepatol 2005;17:917–21. 8. Ganesan B, Rajesh R, Anandan R, Dhandapani N. Biochemical studies on the protective effect of betaine on mitochondrial function in experimentally induced myocardial infarction in rats. J Health Sci 2007;53:671–81. 9. Ganesan B, Anandan R, Rajesh R. Protective effect of betaine on changes in lipid profile, lipoproteins and fatty acid composition in experimentally

421


Şehirli et al. Protective effect of betaine against burn-induced pulmonary injury in rats induced myocardial infarction in Wistar rats. Int J Biomed Pharm Sci 2008;2:65–9. 10. Ganesan B, Buddhan S, Anandan R, Sivakumar R, AnbinEzhilan R. Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats. Mol Biol Rep 2010;37:1319–27. 11. Parihar A, Parihar MS, Milner S, Bhat S. Oxidative stress and anti-oxidative mobilization in burn injury. Burns 2008;34:6–17. 12. Meakins JL. Etiology of Multiple Organ Failure. J Trauma 1990;30:165–8. 13. Weik C, Warskulat U, Bode J, Peters-Regehr T, Häussinger D. Compatible organic osmolytes in rat liver sinusoidal endothelial cells. Hepatology 1998;27:569–75. 14. Sener G, Sehirli AO, Satiroğlu H, Keyer-Uysal M, Yeğen BC. Melatonin improves oxidative organ damage in a rat model of thermal injury. Burns 2002;28:419–25. 15. Martinek RG. A rapid ultraviolet spectrophotometric lactic dehydrogenase assay. Clin Chim Acta 1972;40:91–9. 16. Beuge JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;53:302–11. 17. Beutler E. Glutathione in red blood cell metabolism. A manual of biochemical methods. New York: Grune&Stratton, 1975. p. 112–4. 18. Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 1990;24:285–95. 19. Reading HW, Isbir T. The role of cation-activated ATPases in transmitter release from the rat iris. Q J Exp Physiol Cogn Med Sci 1980;65:105–16. 20. Fiske CH, SubbaRow Y. The colorimetric determination of phosphorus. J Biol Chem 1925;66:375-400. 21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75. 22. Sehirli O, Sener E, Sener G, Cetinel S, Erzik C, Yeğen BC. Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines. Peptides 2008;29:1231–40. 23. Martin LF, Booth FV, Reines HD, Deysach LG, Kochman RL, Erhardt LJ, et al. Stress ulcers and organ failure in intubated patients in surgical

intensive care units. Ann Surg 1992;215:332–7. 24. O’Sullivan ST, Lederer JA, Horgan AF, Chin DH, Mannick JA, Rodrick ML. Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection. Ann Surg 1995;222:482–92. 25. Schwacha MG, Somers SD. Thermal injury induces macrophage hyperactivity through pertussis toxin-sensitive and -insensitive pathways. Shock 1998;9:249–55. 26. Yu J, Sauter S, Parlesak A. Suppression of TNF-alpha production by Sadenosylmethionine in human mononuclear leukocytes is not mediated by polyamines. Biol Chem 2006;387:1619–27. 27. Lv S, Fan R, Du Y, Hou M, Tang Z, Ling W, et al. Betaine supplementation attenuates atherosclerotic lesion in apolipoprotein E-deficient mice. Eur J Nutr 2009;48:205–12. 28. Sağlam E, Sehirli AO, Ozdamar EN, Contuk G, Cetinel S, Ozsavcı D, et al. Captopril protects against burn-induced cardiopulmonary injury in rats. Ulus Travma Acil Cerrahi Derg 2014;20:151–60. 29. Wettstein M, Häussinger D. Cytoprotection by the osmolytes betaine and taurine in ischemia-reoxygenation injury in the perfused rat liver. Hepatology 1997;26:1560–6. 30. Haycock JW, Ralston DR, Morris B, Freedlander E, MacNeil S. Oxidative damage to protein and alterations to antioxidant levels in human cutaneous thermal injury. Burns 1997;23:533–40. 31. Kanbak G, Dokumacioglu A, Tektas A, Kartkaya K, Erden Inal M. Betaine (trimethylglycine) as a nutritional agent prevents oxidative stress after chronic ethanol consumption in pancreatic tissue of rats. Int J Vitam Nutr Res 2009;79:79–86. 32. Sener G, Sehirli O, Erkanli G, Cetinel S, Gedik N, Yeğen B. 2-Mercaptoethane sulfonate (MESNA) protects against burn-induced renal injury in rats. Burns 2004;30:557–64. 33. Ganesan B, Anandan R, Yathavamoorthi R. Supplementation of betaine attenuates experimentally induced gastric mucosal damage in Wistar albino rats. Int J Biol Chem 2010;4:79–89. 34. Kim SK, Kim YC, Kim YC. Effects of singly administered betaine on hepatotoxicity of chloroform in mice. Food Chem Toxicol 1998;36:655–61.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçanlarda yanığa bağlı olarak gelişen akciğer hasarına karşı betain’in koruyucu etkisi Dr. Ahmet Özer Şehirli,1,2 Dr. Burcu Satılmış,3 Dr. Şermin Tetik,4 Dr. Şule Çetinel,5 Dr. Berrak Yeğen,6 Dr. Aslı Aykaç,7 Dr. Göksel Şener1 Marmara Üniversitesi Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, İstanbul Yakın Doğu Üniversitesi, Diş Hekimliği Fakültesi, Lefkoşa-KKTC Acıbadem Maslak Hastanesi, Eczacılık Bölümü, İstanbul 4 Marmara Üniversitesi Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul 5 Marmara Üniversitesi Tıp Fakültesi, Histoloji-Embriyoloji Anabilim Dalı, İstanbul 6 Marmara Üniversitesi Tıp Fakültesi, Fizyoloji Anabilim Dalı, İstanbul 7 Yakın Doğu Üniversitesi Tıp Fakültesi, Biyofizik Anabilim Dalı, Lefkoşa-KKTC 1 2 3

AMAÇ: Bu çalışma, yanığa bağlı olarak gelişen akciğerdeki oksidatif hasara karşı betain tedavisinin olası koruyucu etkisini tanımlamak için tasarlandı. GEREÇ VE YÖNTEM: Yanık oluşturmak için sırt derileri traş edilmiş Wistar albino türü sıçanlar, eter anestezisi altında 10 saniye süreyle 90°C suya tutuldu. Yanık oluşturulmadan evvel 21 gün süre ile betain 250 mg/kg dozunda oral olarak uygulandı ve yanık oluşturulduktan sonra tek doz betain uygulaması yapıldı. Kontrol grubunda ise aynı işlem uygulandıktan sonra sırt bölgeleri 10 saniye süreyle 25°C suya tutuldu. Deney sonunda sıçanlar dekapite edildi ve kan numuneleri proinflamatuvar sitokinleri (tümör nekroz faktör- [TNF-] and interlökin 1 beta [IİL-1]) ve LDH aktivitesini analiz etmek için toplandı. Akciğer doku örnekleri histolojik analizlarin yanı sıra MDA ve GSH seviyelerini, MPO ve Na+, K+-ATPaz aktivitesini belirlemek için alındı. BULGULAR: Yanık hasarı sitokin seviyelerinde ve LDH aktivitesinde önemli derecede artışa neden oldu. Yanık hasarına bağlı olarak akciğer dokularında MDA seviyeleri ve MPO aktivitesi yüksek, GSH seviyeleri ile Na+, K+-ATPaz aktivitesi düşük bulundu. TARTIŞMA: Bu çalışmanın bulgularına göre yanığın serum ve dokuda neden olduğu hasarın betain ile anlamlı olarak azaldığı saptanmıştır. Anahtar sözcükler: Akciğer hasarı; betain; oksidatif stres; sitokinler; termal travma. Ulus Travma Acil Cerrahi Derg 2016;22(5):417–422

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EXPERIMENTAL STUDY

Efficiacy of resveratrol and quercetin after experimental spinal cord injury Ulvi Çiftçi, M.D.,1 Emre Delen, M.D.,2 Murat Vural, M.D.,3 Onur Uysal, M.D.,4 Didem Turgut Coşan, M.D.,5 Canan Baydemir, M.D.,6 Fulya Doğaner, M.D.5 1

Departmant of Neurosurgery, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

2

Department of Neurosurgery, Trakya University Faculty of Medicine, Edirne-Turkey

3

Departmant of Neurosurgery, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir-Turkey

4

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

5

Department of Medical Biology, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir-Turkey

6

Department of Biostatistics, Kocaeli University Faculty of Medicine, Kocaeli-Turkey

ABSTRACT BACKGROUND: The aim of this study was to investigate the effect of natural antioxidants resveratrol and quercetin on oxidative stress and secondary cell damage in rats with acute spinal cord injury. METHODS: In this experimental study, 42 male Sprague-Dawley rats were used. Spinal cord injury was performed with clip compression method at level of T4-5. The study was conducted using 6 groups: control, trauma, trauma and solvent, trauma and resveratrol, trauma and quercetin, and trauma with combined resveratrol and quercetin. All rats were euthanized 48 hours after the procedure. Effects of resveratrol and quercetin on serum and tissue total antioxidant capacity and paraoxanase activity level were examined. RESULTS: Compared to trauma group, there was a significant increase in total antioxidant capacity and paraoxanase activity level in resveratrol, quercetin, and combined treatment groups. There was no significant difference between resveratrol and quercetin groups with regard to total antioxidant capacity and paraoxanase activity level. Total antioxidant capacity and paraoxanase activity level were significantly higher in solvent group than trauma group. In histopathological evaluation, there was a decrease in polymorphonuclear leukocyte infiltration in solvent, resveratrol, quercetin, and combined treatment groups. CONCLUSION: Biochemical and histological staining results of present study showed that resveratrol and quercetin may be effective in preventing secondary damage in spinal cord injury. Keywords: Antioxidant; experimental spinal cord injury; quercetin; resveratrol.

INTRODUCTION Spinal cord injury (SCI) is a clinical condition that often causes devastating outcomes such as permanent incapacity, especially in the younger population. It is well known that SCI is a type of trauma with no known effective therapeutic methods, and accordingly it is still difficult to estimate progAddress for correspondence: Ulvi Çiftçi, M.D. Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Nöroşirürji Kliniği, İstanbul, Turkey Tel: +90 212 - 414 7171 E-mail: drulvi26@hotmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):423–431 doi: 10.5505/tjtes.2016.44575 Copyright 2016 TJTES

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nosis. Poor prognosis and devastating outcomes of SCI justify scientific interest in the pathophysiology of SCI as well as in protective strategies and development of treatment options.[1,2] Resveratrol and quercetin are naturally occurring antioxidative compounds that are referred to as polyphenols. Resveratrol reduces oxidation of low-density lipoprotein (LDL) by chelating copper (II) and phagocytizing oxygen free radicals. It also inhibits platelet aggregation and prevents thrombus formation and atherosclerosis, acting as a therapeutic agent to prevent potential cardiovascular disease.[2–5] Quercetin has a broad range of pharmacological characteristics such as anticancer, antiviral, antihistaminic, antitumoral, immunomodulatory, antioxidant, and anti-inflammatory properties.[5–10] Recently, there have been studies conducted on antioxidant effects of these agents. The current study explored therapeutic effects and antioxidant properties of post-SCI administered resveratrol and quercetin on secondary cell damage. 423


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immediate removal with clip holder. Post-SCI paraplegia was observed in all rats. Resveratrol and quercetin were dissolved in dimethyl sulfoxide (DMSO) and single dose 1 hour following SCI was administered. All rats were euthanized 48 hours after procedure. All procedures and group data are summarized in Table 1.

MATERIALS AND METHODS Male Sprague-Dawley rats (weight: 250±50 g; n=42) were supplied for the study by the experimental research center of Eskisehir Osmangazi University. Animals had 2-week period of adaptation to surroundings before initiation of study. They were housed in polycarbonate cages in a temperature- and humidity-controlled room (21±10°C and 45-55%, respectively) with 12/12 reversed light cycle. They were fed with standard rat chow and allowed to drink ad libitum. Procedures regarding animal care, surgery, and sample preparation were approved by the institutional animal care and experiments committee of Eskisehir Osmangazi University Faculty of Medicine. Regulations and guidelines for the care and use of laboratory animals of institutional animal care and experiments committee of Eskisehir Osmangazi University Faculty of Medicine (19.08.2009/130) were observed, as well as US National Institutes of Health guidelines regarding the care and use of animals for experimental procedures.

Biochemical Analyses Thoracic cavity of rats was opened under general anesthesia in order to determine total antioxidant status (TAS) level and paraoxonase-1 (PON-1) activity. A blood sample of 3 mL was drawn from heart, centrifuged at 1000 rpm for 10 minutes, and plasma was collected. Tissue samples and spinal cord samples of approximately 15 mm in length were taken from all groups and frozen in liquid nitrogen. Samples were transferred to tubes containing 1 mL 1x phosphate buffer saline and processed in ultrasonic homogenizer. The resultant homogenate was centrifuged at 3500 rpm for 15 minutes and supernatant was used for measurements. In plasma and tissue homogenates, TAS level was read using Shimadzu UV-1601 spectrophotometer (Shimadzu Corp., Kyoto, Japan) at absorbance level of 660 nm according to TAS assay kit (Rel Assay Diagnostics, Gaziantep, Turkey) procedures, while PON-1 activity was measured using same device at absorbance level of 412 nm according to the PON-1 kit (Rel Assay Diagnostics, Gaziantep, Turkey) procedures.

Surgical Procedure The experimental SCI model was applied to 42 rats divided into 6 groups. Sedation was ensured with intramuscularly (i.m.) administered xylazine (Rompun; Bayer AG, Leverkusen, Germany) at dose of 10 mg/kg, followed by ketamine hydrochloride (Ketalar; Pfizer, New York, NY, USA) i.m. at dose of 50mg/kg for general anesthesia. Rivlin-Tator compression model (1978) was used: Surgical mark point was spinous process of T2 vertebrae, the most remarkable point of the rat spine. The area from T3 to T6 was shaved, and local surgery site antisepsis and environmental isolation were ensured. Midline skin incision was made through cutaneous and subcutaneous layers. Fascia was opened and paravertebral muscles were subperiostally lateralized. T4-T5 laminectomy was performed. Spinal cord was exposed and an aneurysm clip with extradural closing pressure of 50 g (Yaşargil clip FE 619K, Aesculap AG, Tuttlingen, Germany) was used to induce SCI. In SCI groups, the clip was in place for 1 minute followed by

Histological Examinations Approximately 15 mm-long samples of spinal cord taken from control and experiment groups for histological evaluation included white matter, grey matter, and trauma site. All specimens were carefully excised and fixed in neutral buffered formalin for histological analyses. After fixation, tissue was embedded in paraffin and serial sections (4 μm) were prepared for each paraffin block; on average, 50 sections were collected per rat. Sections were stained with hematoxylin and eosin for assessment of SCI. Digital images were obtained using Olympus BX-61 microscope (Olympus Corp., Tokyo, Japan) with a

Table 1. Procedures performed and substances used according to experiment group Group n

Procedure

T4 and T5 laminectomy

Substance

Spinal cord DMSO injury

Resveratrol (dissolved in DMSO)

Quercetin (dissolved in DMSO)

C

7 √

SCI

7 √

SCI+DMSO

7

0.3 mL i.p.

SCI+R

7

100 mg/kg i.p.

SCI+Q

7

200 mg/kg i.p.

SCI+R+Q

7

100 mg/kg i.p.

200 mg/kg i.p.

C: Control group; DMSO: Dimethyl sulfoxide; i.p: Intraperitoneal; Q: Quercetin; R: Resveratrol; SCI: Spinal cord injury group; SCI+DMSO: Post-SCI DMSO group; SCI+Q: Post-SCI quercetin group; SCI+R: Post-SCI resveratrol group; SCI+R+Q: Post-SCI combined treatment group.

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DP70 digital camera. Histological scoring of SCI was as follows: no damage (0), very mild (1), mild (2), moderate (3), and severe (4). Tissue samples were also examined for hemorrhage, edema, necrosis, axonal swelling, chromatolysis, polymorphonuclear leukocyte (PMNL) infiltration and microglia/macrophage/MNL (mononuclear leukocytes) infiltration (Dobrowolski et al. 2011; Hausmann 2003; İş et al. 2006; Oyinbo 2011).

ter of groups. When multiple comparison tests were examined in order to determine inter-group differences, significant increase was observed in hemorrhage in SCI and post-SCI DMSO groups compared with control group (p<0.05) (Figs. 1a, c, d, 2a, b). It was observed that resveratrol administered in post-SCI period was more effective than quercetin in terms of eliminating hemorrhage (Figs. 2c, 3c).

Statistical Analyses

Remarkable differences were also observed in white and gray matter of groups with regard to parameter of edema. Significant increase was observed in SCI and post-SCI DMSO groups in comparison with control group (p<0.05). Particularly, a regression was observed in edema with post-SCI resveratrol and post-SCI combine treatment groups versus SCI group (Figs. 2c, 4c).

Statistical analyses were performed using Statistical Package for the Social Sciences for Windows, version 11.0 (SPSS Inc., Chicago, IL, USA) and SigmaStat 3.5 (Statcon Inc., B. Schäfer, Witzenhausen, Germany) software packages. KolmogorovSmirnov normality test was used for data with normal distribution. Groups were compared using analysis of variance (ANOVA) for normally distributed data, and Tukey’s HSD test for multiple comparisons; Kruskal-Wallis ANOVA test was used for non-normally distributed data. Results were expressed as mean±SD or median (25%–75% percentiles). A p value <0.05 was considered statistically significant.

RESULTS Biochemical Results Serum and tissue TAS and PON-1 levels were lower in SCI group in comparison with the control group (p<0.05). Although post-SCI resveratrol and quercetin increased serum and tissue TAS and PON-1 levels in comparison with SCI group, there was no statistically significant difference between the 2 groups. The most remarkable increase was observed in post-SCI combined treatment group (p<0.05) (Table 2).

Histological Results When spinal cord was examined with regard to hemorrhage, a remarkable difference was found in white and gray mat-

There were important differences in necrosis of white and gray matter, as well. Significant increase was observed in SCI and post-SCI DMSO groups compared with control group (p<0.05) (Fig. 1b, 2b). It was observed that post-SCI resveratrol was effective achieving in regression of necrosis (Fig. 2d, 3a). With regard to PMNL infiltration, there were important inter-group differences in white matter. Significant increase was observed in PMNL infiltration in SCI group in comparison with control group (p<0.05) (Fig. 1d). There was significant decrease in post-SCI combined treatment group in comparison with SCI group, and regression was observed in white matter of all groups (p<0.05). There was significant difference between groups with regard to PMNL infiltration to the vessel wall and subarachnoid space. A significant increase was observed in PMNL infiltration to the vessel wall in the SCI group in comparison with control group (p<0.05). There was a significant decrease in PMNL infiltration in post-SCI resve-

Table 2. Serum and tissue TAS and PON-1 values of all groups (mean±SD or median 25%–75% percentiles)

Serum TAS Level (mmoL Trolox Eq/L)

Tissue TAS Level (mmoL Trolox Eq/L)

Serum PON-1 Level (U/L)

Tissue PON-1 Level (U/L)

Median (25%–75% per.)

Mean±SD

Mean±SD

Median (25%–75% per.)

C

1.65 (1.62–1.66)

0.75±0.007

146.28±2.61

82.91 (80.06–84.37)

SCI

0.63 (0.62–0.64)

0.15±0.02

67.11±2.89

35.75 (34.46–39.61)

SCI+DMSO

0.89 (0.89–0.96)

0.29±0.01

81.18±4.05

43.98 (40.24–48.50)

SCI+R

1.24 (1.23–1.27)

0.44±0.03

104.71±1.81

61.58 (53.95–62.64)

SCI+Q

1.23 (1.10–1.24)

0.42±0.03

100.93±2.14

58.75 (52.95–60.74)

SCI+R+Q

1.39 (1.36–1.46)

0.61±0.02

118.41±1.69

70.01 (66.05–71.35)

Statistics H=38.916a F=655.156a F=772.748a H=38.380a Statistics, p

<0.001

<0.001

<0.001

<0.001

a: All groups different from each other (p<0.05) except SCI+R and SCI+Q (p>0.05); C: Control group; DMSO: Dimethyl sulfoxide; i.p: Intraperitoneal; PON-1: Paraoxonase-1; Q: Quercetin; R: Resveratrol; SCI: Spinal cord injury group; SCI+DMSO: Post-SCI DMSO group; SCI+Q: Post-SCI quercetin group; SCI+R: Post-SCI resveratrol group; SCI+R+Q: Post-SCI combined treatment group; TAS: Total antioxidant status.

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ratrol, quercetin and combined treatment groups compared with SCI group (p<0.05). When microglia/macrophage/MNL infiltration was examined, important differences were observed in white and gray matter. Microglia/macrophage/MNL infiltration was not observed in white matter of control and SCI groups or post-SCI resveratrol group. Significant increase in microglia/macrophage/ MNL infiltration was observed in white and gray matter of

(a)

It was found that resveratrol and quercetin had no beneficial effect on axonal swelling induced with SCI. It was also determined that chromatolysis had non-significant

(b)

(c)

(d)

(a)

(b)

(c)

(d)

426

quercetin and combined treatment groups in comparison with SCI group (p<0.05) (Fig. 3b, 4c). Therefore, it was determined that quercetin was more effective than resveratrol against increased microglia/macrophage/MNL infiltration.

Figure 1. Spinal cord tissue morphology indicated by hematoxylineosin staining in control and SCI groups. (a)Control group; normal view. H&E, Scale Bar 200 µm. (b) SCI group; moderate axonal swelling (arrow) and necrosis in the white matter. H&E, Scale Bar 20 µm. (c) SCI group; severe axonal swelling (arrow), hemorrhage (asterisk), edema (arrow head) and necrosis in the white matter. H&E, Scale Bar 200 µm. (d) SCI group; moderate PMNL infiltration (arrow) in vascular wall, severe axonal swelling (arrow head), hemorrhage (asterisk), edema and necrosis in the white matter. H&E, Scale Bar 20 µm. Figure 2. Spinal cord tissue morphology indicated by hematoxylin-eosin staining in post-SCI DMSO and postSCI Resveratrol groups. (a) Post-SCI DMSO group; moderate hemorrhage (asterisk), edema, axonal swelling (arrow head), and severe necrosis in the white matter. H&E, Scale Bar 100 µm. (b) Post-SCI DMSO group; mild microglia/macrophage/MNL infiltration (thick arrow) and severe hemorrhage (asterisk), edema (arrow head) and necrosis (thin arrow) in the white matter. H&E, Scale Bar 20 µm. (c) Post-SCI Resveratrol group; severe hemorrhage (asterisk), edema (arrow head), necrosis, axonal swelling (thin arrow) and chromatolysis (thick arrow) in the White and gray matter. H&E, Scale Bar 100 µm. (d) Post-SCI Resveratrol group; severe axonal swelling (arrow) and necrosis (arrow head) in the white matter. H&E, Scale Bar 20 µm.

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Çiftçi et al. Efficiacy of resveratrol and quercetin after experimental spinal cord injury

(a)

(b)

(c)

Figure 3. Spinal cord tissue morphology indicated by hematoxylin-eosin staining in post-SCI Quercetin group. (a) Post-SCI Quercetin group; mild chromatolysis (arrow) and necrosis in the gray matter. H&E, Scale Bar 20 µm. (b) Post-SCI Quercetin group; severe microglia/ macrophage/MNL infiltration (arrow) in the white matter. H&E, Scale Bar 20 µm. (c) Post-SCI Quercetin group; severe hemorrhage (asterisk), edema (arrow head), necrosis (thick arrow) and mild microglia/macrophage/MNL infiltration (thin arrow) in the white matter. H&E, Scale Bar 20 µm.

(a)

(b)

(c)

Figure 4. Spinal cord tissue morphology indicated by hematoxylin-eosin staining in Post-SCI combined treatment group. (a) Post-SCI combined treatment group; mild chromatolysis (arrow) and necrosis (arrow head) in the gray matter. H&E, Scale Bar 20 µm. (b) Post-SCI combined treatment group; severe chromatolysis (arrow) in the gray matter. H&E, Scale Bar 20 µm. (c) Post-SCI combined treatment group; moderate hemorrhage (asterisk), edema, necrosis (thick arrow), axonal swelling (thin arrows) and microglia/macrophage/MNL infiltration (arrow head) in the white matter. H&E, Scale Bar 50 µm.

decrease trend in post-SCI combined treatment group in comparison with SCI group (Fig. 4a, b). Considering all available histological findings, the notable common finding was that PMNL infiltration, an indicator of primary response, had statistically significant decrease in post-SCI resveratrol, quercetin, and combined treatment groups (p<0.05), and it had tendency to completely disappear. It was observed that indicator of secondary response, microglia/macrophage/MNL infiltration, significantly increased in post-SCI quercetin and combined treatment groups (p<0.05). When all available results were examined, it was seen that resveratrol is more efficient in primary response and quercetin is more efficient in secondary response, and most effective result was obtained in post-SCI combined treatment group (Table 3).

DISCUSSION Resveratrol produces anti-inflammatory and anti-anaphylactic effects by influencing arachidonic acid metabolism. It possesses antibacterial, anti-cancerous and anti-mutation effects, and inhibits protein kinase activity. All those properties indicate that resveratrol could affect pathophysiological processes of inflammatory or traumatic reactions.[2,3,5] Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

Yang and Piao demonstrated that resveratrol and methylprednisolone (MP) had protective effect against secondary damage that occurred following SCI.[2] Moreover, they determined that resveratrol had effect on post-SCI energy metabolism, inhibition of lipid peroxidation was more effective, and resveratrol had potent therapeutic effect on SCI. Recent investigations indicate that resveratrol is potential antioxidant, since it prevents formation of free radicals in tissue such as red cell membrane, heart, liver, brain, and kidney; prevents functional injury and improves nerve function; and promotes restoration after trauma. Resveratrol is a candidate as therapeutic agent to ameliorate neurodegenerative processes. Kızıltepe et al. demonstrated that resveratrol protects spinal cord against ischemia-reperfusion damage by reducing oxidative stress and increasing free nitric oxide (NO).[11] In s study conducted by Cemil et al., post-SCI effects of curcumin and MP were compared in biochemical and histopathological terms. [12] Curcumin, another polyphenol, has antioxidative, anticancerous, and anti-inflammatory effects. In curcumin group, tissue malondialdehyde (MDA) level decreased and levels of antioxidant enzymes copper-zinc superoxide dismutase, catalase, and phospholipid hydroperoxide glutathione peroxidase increased. Moreover, it was demonstrated that curcumin histopathologically protected tissue integrity. In rats with in427


Çiftçi et al. Efficiacy of resveratrol and quercetin after experimental spinal cord injury

Table 3. Histological analysis results of all groups (median 25%-75% percentiles)

CG

SCI

SCI+DMSO

SCI+R

SCI+Q

SCI+R+Q

Analysıs (p)

3 (2–3)

24.906 (<0.001)a,b,d

Hemorrhage

WM

0 (0–0) 4 (2.25–4) 3 (2.25–3.75) 2 (2–2.50) 3.50 (3–4)

GM

0 (0–0) 3 (1.25–4)

3 (2–3)

0 (0–0.50)

2 (1–4)

1.50 (0–2)

23.722 (<0.001)a,b,d

Edema

WM

0 (0–0) 4 (2.50–4)

3 (3–4)

3 (3–4)

4 (4–4)

3.50 (2–4)

24.405 (<0.001)a,b,d

GM

0 (0–0) 4 (1.25–4)

2 (2–2.75)

2 (1–2)

2.50 (2–3)

2 (1–2)

22.033 (<0.001)a,b,d

Necrosis

WM

0 (0–0) 4 (3.25–4)

4 (3–4)

2 (2–3)

4 (3–4)

3 (2–3.50)

27.532 (<0.001)a,b,d

GM

0 (0–0) 3 (2.25–3)

3 (3–3)

2.50 (2–3)

3 (3–4)

2 (2–3)

24.518 (<0.001)a,b,d

PMNL infiltration

WM

0 (0–0)

3 (2–4)

0 (0–0)

0.50 (0–1)

1 (0–2)

0 (0–0.50)

28.831 (<0.001)a,f,h

GM

0 (0–0)

2 (0–2)

0 (0–0)

0 (0–0)

0 (0–0)

0 (0–0)

16.671 (>0.05)

WW 0 (0–0)

3 (3–4)

2 (0–4)

0 (0–0.50)

0 (0–0)

0 (0–0)

26.928 (<0.001)a,g,h

SAS

0 (0–0)

3 (3–4)

3 (0–4)

0 (0–0.50)

0 (0–1)

0 (0–0)

21.086 (<0.001)a,h

Microglia/macrophage/MNL

WM

0 (0–0)

0 (0–0)

2 (2–2.75)

1 (1–2)

3 (3–4)

3 (3–3)

39.506 (<0.001)d,l

Infiltration

GM

0 (0–0)

0 (0–0)

2 (2–2)

0 (0–1.50)

2 (2–4)

3 (2–3)

37.203 (<0.001)d,e,g,k,l

3 (2.25–4)

3 (3–4)

4 (3–4)

3 (2.50–4)

22.100 (<0.001)a,c,d

3 (3–4)

3 (3–3)

3.50 (3–4) 2 (1.50–3)

27.109 (<0.001)b,c,d

Axonal swelling

0 (0–0) 4 (2.50–4)

Chromatolysis

0 (0–0)

3 (2–3)

0: No damage; 1: Very mild; 2: Mild; 3: Moderate; 4: Severe. a: p<0.05 for control group and SCI group; b: p<0.05 for control group and SCI+DMSO group; c: p<0.05 for control group and SCI+R group; CG: Control group; D: p<0.05 for control group and SCI+Q group; DMSO: Dimethyl sulfoxide; E: p<0.05 for control group and SCI+R+Q group; F: p<0.05 for SCI group and SCI+DMSO group; G: p<0.05 for SCI group and SCI+Q group; GM: Gray matter; H: p<0.05 for SCI group and SCI+R+Q group; K: p<0.05 for SCI+R group and SCI+Q group; L: p<0.05 for SCI+R group; MNL: Mononuclear leukocytes; PMNL: Polymorphonuclear leukocyte; Q: Quercetin; R: Resveratrol; SAS: Subarachnoid space; SCI: Spinal cord injury group; SCI+DMSO: Post-SCI DMSO group; SCI+Q: Post-SCI quercetin group; SCI+R: Post-SCI resveratrol group; SCI+R+Q: Post-SCI combined treatment group; VW: Vessel wall; WM: White matter.

duced SCI, it was found that curcumin was as biochemically and histopathologically effective as MP in functional improvement. Ates et al. investigated the effects of resveratrol and MP on induced SCI and found that MDA, NO and xanthine oxidase levels were lower and glutathione groups were higher in resveratrol and resveratrol+MP (combination) groups in comparison with just MP group.[13] It was observed that neurological improvement was better in resveratrol and combined treatment group relative to MP alone group. No significant histological difference was found in the treated groups. It was found in the current study that resveratrol was as effective as MP on secondary damage that occurs in post-SCI period and combined treatment offered no extra protection in chronic phase of SCI. It was determined that resveratrol and quercetin combination ameliorated post-traumatic oxidative stress and led to regression of edema. Therapeutic value and mechanisms of resveratrol on SCI should be studied further. One means of antioxidant action exerted by quercetin involves scavenging free radicals, such as superoxide radicals generated by xanthine and xanthine oxidase. The antioxidant capacity of this molecule may be a very significant function and responsible for many of the beneficial effects. Quercetin interferes with the production of reactive oxygen species and reduces tissue damage through chelating effect and elimination of lipid peroxidation.[5–7,10] It has been reported that quercetin is effective in prevention 428

of oxidative damage to DNA or to cell membrane. One possible mechanism is that quercetin stabilizes lipid membranes and protects lipid peroxidation by exerting free radical scavenging effects. Quercetin is characterized by strong oxygen radical scavenging property and good metal chelating. Quercetin diffuses into membranes at high concentrations, resulting in antioxidative effect, and thus, it may scavenge oxyradicals at several sites through lipid bilayer. Pentahydroxyflavone structure possibly allows it to chelate metal ions via orthodihydroxy phenolic structure and thereby scavenge lipid alkoxyl and peroxyl radicals. It has also been suggested that quercetin acts as an antioxidant by inhibiting oxidative enzymes such as xanthine oxidase, lipoxygenase, and nicotinamide adenine dinucleotide phosphate oxidase. Inhibition of these enzymes is also responsible for attenuation of oxidative stress, as they play key role in initial process of free radical-induced cellular damage. Further, it has been reported that quercetin metabolites can also inhibit peroxynitrite-mediated oxidation, similar to free quercetin. In addition to direct hydrogen-donating properties, attention has focused on influence of quercetin on signaling pathways and its indirect interaction with endogenous antioxidant defense system.[5,10] Epidemiological studies have indicated beneficial effects of quercetin in neural protection.[14] Cerebral neuroprotective effect of quercetin derives from anti-oxidative effect and free radical scavenging property.[15,16] In a study conducted by Genovese et al., the authors investigated effect of HyperiUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Çiftçi et al. Efficiacy of resveratrol and quercetin after experimental spinal cord injury

cum perforatum extract on neuroprotection and neuronal improvement in rats after SCI was induced.[17] Hypericum perforatum extract comes from an herb that is a member of polyphenol group and contains flavonoid and phenolic acid. It was determined that Hypericum perforatum extract improved spinal cord inflammation, tissue damage, and PMNL infiltration. It was also found to improve neuronal function. In an experimental study conducted by Schültke et al. (2010), it was demonstrated that the extract protected tissue integrity in the area of SCI and success rate of the treatment was dependent on frequency of administration and total dose.[18] Schültke et al. (2003) demonstrated in other experimental study that amelioration of secondary damage via chelation of iron is an important mechanism in functional improvement after SCI develops that is supported by quercetin.[19] Although primary physiological role of PON-1 is not still completely known, recent studies have demonstrated that it is associated with high-density lipoprotein (HDL) cholesterol and prevents lipid peroxidation by playing protective role against oxidative modification of LDL cholesterol in addition to having antioxidant and anti-inflammatory activities.[20–22] In patients with diseases characterized by increased oxidative damage, the higher tendency of HDL for peroxidation is considered to be related to decreased PON-1 activity.[23] It has been observed that PON-1 offers protection against lipid peroxidation damage caused by free radicals on cell membranes and lipoproteins.[24] In a study conducted by Rael et al., plasma oxidation reduction potential, PON-1 and arylesterase activity were measured in 39 patients with multiple traumas and results were compared with those of 10 healthy volunteers.[25] It was determined that PON-1 and AE activity were significantly lower in patients with multiple traumas ,and those parameters may be beneficial when severity of trauma and potential efficiency of treatment are examined. In the current study, significantly higher serum and tissue TAS and PON-1 activity levels found in post-SCI resveratrol group relative to SCI and post-SCI DMSO groups are consistent with findings of Ates et al (2006; 2007) indicating increased glutathione peroxidase level in rats given resveratrol after SCI and head trauma.[13,25] Elmali et al. demonstrated that resveratrol significantly reduced MDA level in ischemia/reperfusion damage of skeletal muscle.[26] It was also observed in the current study that TAS level, which indicates total antioxidative effect, increased in resveratrol treatment group. It can be speculated that effect derives from anti-oxidative effect and free radical scavenging property of resveratrol as determined in the literature, particularly studies conducted by Ates et al. (2006; 2007).[13,26] The increased level of TAS indicates that resveratrol offers better protection against oxidative damage of the spinal cord. In addition, in the current study it was seen that PON-1 activity increased in rats given resveratrol. As indicated in studies conducted by Elmali et al. and Ray et al., resveratrol may inhibit lipid peroxidation and alleviate LDL oxidation by binding free radicals. Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

We observed in the current study that serum and tissue TAS levels and PON-1 activities were significantly higher in quercetin group relative to SCI and SCI+DMSO groups. Increase may be due to antioxidative effects deriving from free radical scavenging properties. [27,28]

In the present study it was found that serum and tissue TAS levels and PON-1 activities in DMSO group were significantly higher than SCI group and lower than control group. DMSO, which was used as solvent, is a free oxygen radical scavenger, largely specific to hydroxyl radicals. Turan et al. demonstrated substantial neuroprotective effect of DMSO in rabbits with induced spinal cord ischemia/reperfusion damage.[29] In a study conducted by Chiueh et al., it was also demonstrated that DMSO suppressed generation of free radicals in cranial trauma.[30] In the current study, PMNL infiltration was eliminated from white matter of group given DMSO. It was observed that TAS level was significantly higher in comparison with SCI group. As noted by Albin et al. (1986) and Chiueh et al. (1994) with studies published in the literature, it is believed that the increase was secondary to free radical scavenging effects of DMSO.[30,31] Moreover, increased PON-1 activity may be related to effect of DMSO on lipid metabolism. In the present study, serum and tissue TAS levels and PON-1 activity were significantly higher in post-SCI combined treatment group relative to both SCI and resveratrol monotherapy and quercetin monotherapy groups. In a study conducted by Carvalho et al., ganglioside, MP, and gangliozide+MP combination were administered to rats after SCI was induced. [32] It was demonstrated that results obtained in combined treatment group were better than MP monotherapy group. Ates et al. demonstrated that neurological improvement was better in combined treatment group relative to MP monotherapy group.[26] In comparison with monotherapy groups and solvent groups, the significantly higher serum and tissue TAS levels and PON activity in combined treatment group as well as serum and tissue levels almost equal to control group may be due to antioxidative and anti-inflammatory potential of both therapeutic agents and the DMSO. In concordance with these findings, the better results obtained in combined treatment group in the post-SCI period relative to monotherapy groups support idea that those two agents and solvent DMSO have synergistic effect. Elmali et al. demonstrated that resveratrol significantly reduced PMNL infiltration and edema in muscular tissue, changes in length of muscle fibers, and segmented necrosis relative to control group in ischemia-reperfusion injury.[27] As a remarkable common finding, it was observed in the current study that in comparison with SCI group, PMNL infiltration was reduced in the white matter of post-SCI DMSO and combined treatment groups, in the vessel wall of postSCI quercetin and combined treatment groups, and in the subarachnoid space of the post-SCI combined treatment group, the reduction of the infiltration tended to completely 429


Çiftçi et al. Efficiacy of resveratrol and quercetin after experimental spinal cord injury

disappear. It was observed that microglia/macrophage/MNL infiltration significantly increased in the white matter of postSCI quercetin and combined treatment groups in comparison with SCI group, in the gray matter of post-SCI quercetin group in comparison with the SCI and post-SCI resveratrol group, and in gray matter of post-SCI combined treatment group in comparison with post-SCI resveratrol group. This effect may derive from anti-inflammatory effects of two drugs and DMSO.

Conclusions In summary, our results indicate that resveratrol and quercetin combination alleviated post-SCI oxidative stress. Resveratrol was more effective on primary response, while quercetin was more effective on secondary response, and most effective results were obtained in post-SCI combined treatment group. The 2 compounds may have protected the spinal cord against secondary damage due to possible anti-oxidative effects. We believe that more extensive future studies are warranted to include resveratrol and quercetin in the treatment protocol of SCI. Conflict of interest: None declared.

REFERENCES 1. Profyris C, Cheema SS, Zang D, Azari MF, Boyle K, Petratos S. Degenerative and regenerative mechanisms governing spinal cord injury. Neurobiol Dis 2004;15:415–36. 2. Yang YB, Piao YJ. Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin 2003;24:703–10. 3. Li Y, Cao Z, Zhu H. Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. Pharmacol Res 2006;53:6–15. 4. Rubiolo JA, López-Alonso H, Martín-Vázquez V, Fol-Rodríguéz NM, Vieytes MR, Botana LM, et al. Resveratrol inhibits proliferation of primary rat hepatocytes in G0/G1 by inhibiting DNA synthesis. Folia Biol (Praha) 2012;58:166–72. 5. Ross JA, Kasum CM. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 2002;22:19–34. 6. Moutsatsou P. The spectrum of phytoestrogens in nature: our knowledge is expanding. Hormones (Athens) 2007;6:173–93. 7. Chattopadhyay P, Shukla G, Wahi AK. Protective effect of L-arginine against necrosis and apoptosis induced by experimental ischemic and reperfusion in rat liver. Saudi J Gastroenterol 2009;15:156–62. 8. Rajević N, Matković H, Gregorović G, Kovacević G, Knezović L, Kalafatić M. Behavioral, morphological and histopathological effects of sublethal doses of quercetin on the species Polycelis felina (Dalyell). Folia Biol (Krakow) 2013;61:101–6. 9. Ciftci O, Vardi N, Ozdemir I. Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats. Environ Toxicol 2013;28:146–54. 10. Selvakumar K, Bavithra S, Krishnamoorthy G, Venkataraman P, Arunakaran J. Polychlorinated biphenyls-induced oxidative stress on rat hippocampus: a neuroprotective role of quercetin. ScientificWorldJournal 2012;2012:980314. 11. Kiziltepe U, Turan NN, Han U, Ulus AT, Akar F. Resveratrol, a red wine polyphenol, protects spinal cord from ischemia-reperfusion injury. J Vasc

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Surg 2004;40:138–45. 12. Cemil B, Topuz K, Demircan MN, Kurt G, Tun K, Kutlay M, et al. Curcumin improves early functional results after experimental spinal cord injury. Acta Neurochir (Wien) 2010;152:1583–90. 13. Ates O, Cayli S, Altinoz E, Gurses I, Yucel N, Sener M, et al. Neuroprotection by resveratrol against traumatic brain injury in rats. Mol Cell Biochem 2007;294:137–44. 14. Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry JA, Costa G, et al. Neuroprotection by flavonoids. Braz J Med Biol Res 2003;36:1613–20. 15. Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging 2002;23:719–35. 16. Zimmermann M, Colciaghi F, Cattabeni F, Di Luca M. Ginkgo biloba extract: from molecular mechanisms to the treatment of Alzhelmer’s disease. Cell Mol Biol (Noisy-le-grand) 2002;48:613–23. 17. Genovese T, Mazzon E, Menegazzi M, Di Paola R, Muià C, Crisafulli C, et al. Neuroprotection and enhanced recovery with hypericum perforatum extract after experimental spinal cord injury in mice. Shock 2006;25:608–17. 18. Schültke E, Kamencic H, Skihar VM, Griebel R, Juurlink B. Quercetin in an animal model of spinal cord compression injury: correlation of treatment duration with recovery of motor function. Spinal Cord 2010;48:112–7. 19. Schültke E, Kendall E, Kamencic H, Ghong Z, Griebel RW, Juurlink BH. Quercetin promotes functional recovery following acute spinal cord injury. J Neurotrauma 2003;20:583–91. 20. Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 2005;69:541–50. 21. Mackness B, McElduff P, Mackness MI. The paraoxonase-2-310 polymorphism is associated with the presence of microvascular complications in diabetes mellitus. J Intern Med 2005;258:363–8. 22. Baum L, Ng HK, Woo KS, Tomlinson B, Rainer TH, Chen X, et al. Paraoxonase 1 gene Q192R polymorphism affects stroke and myocardial infarction risk. Clin Biochem 2006;39:191–5. 23. Ferretti G, Bacchetti T, Busni D, Rabini RA, Curatola G. Protective effect of paraoxonase activity in high-density lipoproteins against erythrocyte membranes peroxidation: a comparison between healthy subjects and type 1 diabetic patients. J Clin Endocrinol Metab 2004;89:2957–62. 24. Ferretti G, Bacchetti T, Moroni C, Vignini A, Curatola G. Copper-induced oxidative damage on astrocytes: protective effect exerted by human high density lipoproteins. Biochim Biophys Acta 2003;1635:48–54. 25. Rael LT, Bar-Or R, Aumann RM, Slone DS, Mains CW, Bar-Or D. Oxidation-reduction potential and paraoxonase-arylesterase activity in trauma patients. Biochem Biophys Res Commun 2007;361:561–5. 26. Ates O, Cayli S, Altinoz E, Gurses I, Yucel N, Kocak A, et al. Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury. Acta Pharmacol Sin 2006;27:1317–25. 27. Elmali N, Esenkaya I, Karadağ N, Taş F, Elmali N. Effects of resveratrol on skeletal muscle in ischemia-reperfusion injury. Ulus Travma Acil Cerrahi Derg 2007;13:274–80. 28. Ray PS, Maulik G, Cordis GA, Bertelli AA, Bertelli A, Das DK. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med 1999;27(1-2):160–9. 29. Turan NN, Akar F, Budak B, Seren M, Parlar AI, Sürücü S, et al. How DMSO, a widely used solvent, affects spinal cord injury. Ann Vasc Surg 2008;22:98–105. 30. Chiueh CC, Wu RM, Mohanakumar KP, Sternberger LM, Krishna G, Obata T, et al. In vivo generation of hydroxyl radicals and MPTPinduced dopaminergic toxicity in the basal ganglia. Ann N Y Acad Sci

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Çiftçi et al. Efficiacy of resveratrol and quercetin after experimental spinal cord injury 1994;738:25–36. 31. Albin MS, Bunegin L. An experimental study of craniocerebral trauma during ethanol intoxication. Crit Care Med 1986;14:841–6.

32. Carvalho MO, Barros Filho TE, Tebet MA. Effects of methylprednisolone and ganglioside GM-1 on a spinal lesion: a functional analysis. Clinics (Sao Paulo) 2008;63:375–80.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel spinal kord travması sonrası resveratrol ve kuersetin’in etkinliğinin araştırılması Dr. Ulvi Çiftçi,1 Dr. Emre Delen,2 Dr. Murat Vural,3 Dr. Onur Uysal,4 Dr. Didem Turgut Coşan,5 Dr. Canan Baydemir,6 Dr. Fulya Doğaner5 Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Nöroşirürji Kliniği, İstanbul Trakya Üniversitesi Tıp Fakültesi, Nöroşirürji Anabilim Dalı, Edirne Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Nöroşirürji Anabilim Dalı, Eskişehir 4 Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Histoloji Anabilimdalı, Eskişehir 5 Eskişehir Osmangazi Üniversitesi Tıp Fakültesi, Medikal Biyoloji Anabilim Dalı, Eskişehir 6 Kocaeli Üniversitesi Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Kocaeli 1 2 3

AMAÇ: Bu çalışmada, doğal antioksidanlardan olan resveratrol ve kuersetin’in, deneysel spinal kord travması oluşturulmuş sıçanlarda, oksidatif stres ve sekonder doku hasarı üzerine olan etkilerini araştırmak amaçlandı. GEREÇ VE YÖNTEM: Bu deneysel çalışmada, 42 adet Sprague-Dawley cinsi erkek sıçan kullanıldı. Spinal kord hasarı klip kompresyon metodu kullanılarak T4-T5 seviyesinden yapıldı. Çalışma kontrol, travma, travma+çözücü, travma+resveratol, travma+kuersetin ve travma+kombine (resveratrol ve kuersetin) olmak üzere 6 grup üzerinden yürütüldü. İşlemden 48 saat sonra tüm sıçanlar sakrafiye edildi. Resveratrol ve kuersetin’in serum ve dokuda total antioksidan kapasite düzeyi ve paraoksonaz enzim aktivitesine ve histopatolojik bulgulara olan etkisi araştırıldı. BULGULAR: Sonuç olarak resveratrol, kuersetin ve kombine tedavi verilen gruplarda TAOK düzeyi ve PON aktivitesi değerlerinde travma grubuna göre anlamlı bir artma saptandı. Resveratrol ve kuersetin grupları arasında TAOK düzeyi ve PON aktivitesi açısından anlamlı bir farklılık yoktu. Çözücü grubunda TAOK düzeyi ile PON aktivitesi travma grubuna göre anlamlı derecede yüksekti. Histopatolojik incelemede ise sadece çözücü, resveratrol, kuersetin ve kombine tedavi gruplarında PMNL infiltrasyonunun azaldığı görüldü. TARTIŞMA: Çalışmamızdaki biyokimyasal ve histolojik değerlendirmede resveratrol ve kuersetin uygulamasının spinal kord travmasında görülen ikincil hasardan, spinal kordu korumak için kullanılabileceği sonucuna varılmıştır. Anahtar sözcükler: Antioksidan; deneysel spinal kord hasarı; kuersetin; resveratrol. Ulus Travma Acil Cerrahi Derg 2016;22(5):423–431

doi: 10.5505/tjtes.2016.44575

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ORIGIN A L A R T IC L E

Intraorbital foreign bodies: Clinical features and outcomes of surgical removal Ayşe Dolar Bilge, M.D., Hakan Yılmaz, M.D., Bülent Yazıcı, M.D., Faisal Naqadan, M.D. Department of Ophthalmology, Uludağ University Faculty of Medicine, Bursa-Turkey

ABSTRACT BACKGROUND: The present study is an evaluation of clinical features and management outcomes of patients operated on for intraorbital foreign bodies (FBs). METHODS: Medical records of 24 patients who underwent surgery for intraorbital FBs within a 10-year period were reviewed. RESULTS: Twenty patients (83%) were male and 4 (17%) were female (mean age: 28 years; range: 4-69 years). Ten patients (42%) presented within 48 hours of injury, 7 (29%) within 3 days to 1 month, and 7 (29%) more than 1 month after injury. FBs were inorganic in 19 patients (79%), and organic in 5 (21%). Major ocular morbidities were orbital cellulitis (n=5), traumatic optic neuropathy (n=3), globe perforation (n=2), and rupture of rectus muscle (n=2). FBs could be completely removed in all cases. Mean follow-up time was 26 months (range: 1 month-10 years). CONCLUSION: Intraorbital FBs are usually inorganic and metallic, and occur more frequently in young males. Orbital cellulitis, considered typical for organic FBs, may also occur with metallic that perforate lacrimal sac or paranasal sinuses. With appropriate caution, intraorbital FBs can be removed safely with current orbitotomy techniques. Keywords: Intraorbital foreign body; orbitotomy; surgical management.

INTRODUCTION

MATERIALS AND METHODS

Penetration of orbit by foreign body (FB) is a relatively rare type of injury. FBs may be organic or inorganic, and may remain asymptomatic in orbit or may lead to serious morbidities such as cellulitis, optic neuropathy and ocular dismotility. [1] Asymptomatic inorganic FBs may be followed-up without surgical removal. When deciding to perform surgery, potential complications of surgical removal are also considered, as well as composition and possible effects of intraorbital FB.[2] In this report, clinical features and management outcomes of group of patients who underwent orbitotomy for FB removal were reviewed.

Medical records of 24 patients operated on for intraorbital FB between January 2004 and April 2014 were reviewed. The data analyzed included age, gender, time between injury and surgery, features of FB, presence of globe perforation, visual acuity, surgical approach, management outcome, complications and follow-up duration. Patients with intraorbital FB in whom the surgical removal was not indicated or those in whom FBs were located superficially under eyelid skin or conjunctiva were excluded.

Address for correspondence: Bülent Yazıcı, M.D. Uludağ Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, Görükle, 16059 Bursa, Turkey Tel: +90 224 - 295 24 15 E-mail: byazici@uludag.edu.tr Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):432–436 doi: 10.5505/tjtes.2016.20925 Copyright 2016 TJTES

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Patients all underwent complete eye examination. Orbital imaging was performed to determine location and other features of FB. Computed tomography (CT) was used for injuries with metallic FBs, while magnetic resonance imaging (MRI) was preferred for organic FBs. Surgical approach for FB removal was depended on location of FB in orbit. All operations were performed by the same surgeon.

RESULTS Study included 20 (83%) male and 4 (17%) female patients, ranging in age from 4 to 69 years (mean and median ages: 28 and 23 years, respectively). Time between injury and presentation varied from hours to 5 years. Ten patients (42%) preUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Dolar Bilge et al. Intraorbital foreign bodies

sented within 48 hours of injury, 2 (8%) patients presented within 3 to7 days, 5 (21%) between 8 days and 1 month, and 7 (29%) presented more than 1 month after injury. Three patients had previously undergone unsuccessful surgery for FB removal at other medical facilities.

1, 2). Preoperative visual acuity was no light perception in 2 patients, and less than 20/200 in 3 patients.

Associated findings were orbital cellulitis (n=5), chronic cutaneous fistula (n=3), optic neuropathy (n=3), rupture of extraocular muscle (n=2), globe perforation (n=2), and large eyelid defect, intracranial penetration, intraorbital arteriovenous fistula, and chorioretinal atrophy in 1 patient each (Fig.

Surgeries were performed under general and local anesthesia in 20 and 4 patients, respectively. FBs were reached through transcutaneous incisional approach in 18 patients, transconjunctival incision in 6 patients, and were removed successfully in all cases (Fig. 3). Reconstructive procedures, performed during same surgery, included extraocular muscle rupture repair and orbital wall repair in 2 patients, and dural defect repair, eyelid skin grafting, and external dacryocystorhinostomy in 1 patient (Fig. 4, 5). After removal of FB, extraocular motility improved significantly in eyes with restrictive myopathy at presentation (Fig. 4â&#x20AC;&#x201C;7). No patient had any additional impairment of visual acuity after surgery. Three patients who presented with optic neuropathy had no visual improvement after FB removal. No patient had surgical complications or required secondary surgery. Postoperative follow-up ranged from 1 month to 10 years (mean: 26 months).

(a)

(b)

(a)

(b)

(c)

(d)

(c)

(d)

Ten right (42%) and 14 (58%) left orbits were involved. Intraorbital FBs were inorganic and organic in 19 (79%) and 5 (21%) patients, respectively. Inorganic FBs were metallic (n=13), glass (n=5), and plastic (n=1). Metallic FBs were metal fragments (n=8), shotgun pellets (n=2 patients), nail (n=1), shrapnel fragment (n=1) and bullet (n=1 patient). Organic FBs were wood.

Figure 1. (a) A patient with right inferior orbital wooden foreign body that penetrated orbit 1 year previously. (b) FB was removed in several pieces. (c, d) Orbital MRI and CT images show FB (arrows) extending to orbital apex.

Figure 3. (a) Patient with metallic FB at presentation. (b) Axial CT image shows distal portion of FB. (c) Lesion was removed through transconjunctival approach. (d) Early postoperative image of patient.

(a)

(b)

(a)

(b)

(c)

(d)

(c)

(d)

Figure 2. (a) Patient in whom inorganic FB (glass) caused arteriovenous fistula in left orbit. (b, c) Axial CT imaging and intraoperative appearance of FB. (d) Appearance of patient 10 years after surgery.

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Figure 4. (a) Patient with left optic neuropathy and exotropia after shotgun pellet injury 12 days earlier. (b) Axial CT image shows FB. (c, d) Orbital pellet removed, lateral orbital defect reconstructed using polyethylene plate, and lateral rectus muscle repaired.

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Dolar Bilge et al. Intraorbital foreign bodies

(a)

(b)

Figure 5. Eye movement of patient in Figure 4 before (a) and after (b) orbital FB removal.

(a)

(c)

(d)

(b)

(a)

(e)

Figure 6. (a, b) Patient who presented with recurrent cellulitis and lateral gaze limitation had history of plant matter injury 1 year prior. (c) Lesion was hyperdense in contrastenhanced CT images. (d, e) Extraocular movement and orbital symptoms recovered after FB removal.

(b) (c)

Figure 7. Patient in whom metallic FB in medial orbit was complicated with recurrent cellulitis, chorioretinopathy, and restrictive myopathy. (a) Appearance of FB in CT scan. (b, c) One year after surgery. Ocular motility and orbital symptoms improved after FB removal.

DISCUSSION

Detailed PubMed search yielded 5 studies in English literature published in the last 18 years, analyzing results of surgical removal of intraorbital FBs (Table 1).[3â&#x20AC;&#x201C;7] Number of patients in these studies ranged from 19 to 53 (162 patients in total). Three studies[3,5,6] included only patients with intraorbital FB who underwent surgery for FB removal and excluded patients who were not operated on, as in present study. Two studies[4,5] reflected the experience of only 1 medical center, while the others combined patients seen at multiple locations. Three studies[3,4,6] included only metallic or organic FBs, while the other 2[5,7] included all types of foreign material. As in previous studies, most patients with intraorbital FB (54%) in present study were young men of working age (Table 1). In current study, 79% of intraorbital FBs were inorganic, and 54% were metallic. Those rates were 81% and 66%, and 67 and 55% in earlier compatible studies.[5,7] Rate of globe perforation ranged from 0% to 20% in previous studies, and was 8% in present study.[3â&#x20AC;&#x201C;7] As may be expected, this rate was much higher (44% and 20%) in studies that included patients with retained intraorbital FBs.[1,7] 434

The essential consideration in deciding to surgically remove intraorbital FBs is potential complications of leaving FB in place and of removal. Due to associated high risk of orbital cellulitis, all organic FBs should be removed. In present study, 2 patients who had organic FBs retained in orbit for about 1 year, presented with recurrent cellulitis or cutaneous fistula, and restrictive myopathy. In 1 of these, despite history of penetration of fresh tree branch in medial orbit, only a few, small, brown-black, fragile FBs in extensive scar tissue were found during surgery, and removal of these bits of matter resulted in resolution of all inflammatory symptoms and restrictive myopathy (Fig. 6). In the other patient, there was treated wood extending to apex in inferior orbit, and during removal, FB spontaneously divided into two pieces (Fig.1). In current study, in addition to cases with organic FBs, 2 patients with metallic FBs had cellulitis. Both patients had large FBs in posterior medial orbit that penetrated the ethmoid sinuses, and lacrimal sac was injured in 1 patient. Metallic intraorbital FBs that disturb the isolation of lacrimal sac and paranasal sinuses may be complicated by infection. Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Dolar Bilge et al. Intraorbital foreign bodies

Table 1. Several demographic and clinical characteristics of patients with intraorbital foreign bodies as reported in studies Study

Patient Mean age Male patient Early admission Inorganic – Organic FB (%) (n=) (yr) (%) (%)*

Eye perforation Orbital cellulitis (%) (%)

Finkelstein, 1996 27 – 93 – 100–0 7 Nasr, 1998

19

15

79

26

0–100

5

– 58

Fulcher, 2002 40 25 88 75 67.5–32.5 20

25

Shelsta, 2010

23

22

96

43

0–100

0

Callahan, 2013

53

37

89

72

81–15

0

4

Present study, 2015

24

28

83

42

77–22

9

18

*

Early admission was within 48 hours. FB: Foreign body.

Radiological examination of intraorbital FBs has been discussed elsewhere in detail.[3,5,8] In brief, metallic FB can be easily detected with plain radiography or CT, but organic FB may not be easily observed; MRI can provide more detailed information for examination of organic FB.[3] Latter method is contraindicated in cases of metallic FB.

diagnosis is missed or delayed in many instances.[1,16–18] Patients with retained lead pellets should be considered at risk for lead poisoning and follow-up should continue on regular basis.[11] Bullet or pellet fragments, in absence of intracranial extension, can be easily removed during enucleation or evisceration.

Although most metals are inert, some such as iron, copper, and lead may cause serious complications. Location and size of metallic FB is important, as well as chemical structure. Small, inert, and deeply seated metallic objects are usually managed conservatively.[1,5] However, ferromagnetic FBs left in orbit may prevent patients from undergoing MRI in future. Even though these materials can remain harmless for years, they can cause serious ocular injuries when exposed to strong magnetic forces.[7,9] Unfortunately, imaging methods cannot differentiate metallurgical and magnetic properties of metallic FBs. One study found that most metallic intraorbital FBs were found to contain steel, and therefore be ferromagnetic.[7]

For gunshot injuries in which eyeball remains intact, removal of FB may be appropriate if it causes ocular morbidity such as restrictive myopathy, cellulitis, or optic neuropathy. In present study, removal of a BB gun pellet and repair of lateral rectus muscle and lateral orbital wall resulted in remarkable improvement in 1 patient (Fig. 4, 5). If FB is associated with large lacrimal sac laceration, performing external dacryocystorhinostomy during FB removal may obviate need for second, lacrimal surgery.

Gunshot injuries usually lead to severe ocular perforation and permanent visual loss; most patients require removal of the eye after primary repair.[1] However, at time of primary repair, excessive surgical manipulation to remove FB in deep orbit should be avoided. Bullets and pellets are most commonly made with lead core and thin coating alloy (nickel, copper or antimony).[10] Lead does not have magnetic properties, but may cause toxicity due to absorption in the body. Ho et al.[1] observed no progressive ocular complication during follow-up period (range: 6 months-68 years; median: 2 years) in 95% of 43 patients with retained bullet or pellet in orbit. A study published in 1988 reported serum lead levels in normal limits (350 μg/L) in 11 patients with retained intraorbital pellet.[11] However, recent, well-designed studies have reported elevated blood lead levels in patients with retained lead pellets compared to matched controls.[12–15] Bullet fragmentation, multiple bullets, bone fracture, lodgment of bullet near bone or joint, and increased patient age are significant factors associated with high lead levels.[15] Most symptoms of lead toxicity (plumbism) are nonspecific, and Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

Surgical approach for FB removal is determined based on size and location of FB in orbit. FB can be accessed by exploring from entry site or through fistula pathway, if cutaneous fistula is present.[18] It may be difficult to find small FBs encapsulated by fibrous scars in orbit. In such cases, it is helpful to use operation microscope and to follow scar tissue. Some authors use intraoperative fluoroscopy to locate radio-opaque FBs.[19] Organic FBs degrade over time, therefore removal as a single piece may not be possible. These cases may require further dissection in soft tissue for complete removal of FB. Removal of small FBs located in orbital apex may result in serious complications. In current study, however, there was no such case, and removal of FBs in which distal end extended to orbital apex did not result in any complication. Postoperative visual loss has been reported in a few cases in previous studies (at rates of 2.5 to 4%).[3–7] Other complications, including formation of sterile granuloma and eyelid malposition, were also rare.[4,5] Present study supports content that most intraorbital FBs can be removed safely with minimal complication rates using modern orbital surgical techniques. Conflict of interest: None declared. 435


Dolar Bilge et al. Intraorbital foreign bodies

REFERENCES 1. Ho VH, Wilson MW, Fleming JC, Haik BG. Retained intraorbital metallic foreign bodies. Ophthal Plast Reconstr Surg 2004;20:232–6. 2. Cooper W, Haik BG, Brazzo BG. Management of orbital foreign bodies. In: Nesi FA, Levine MR, Lisman RD, editors. Smith’s Ophthalmic Plastic and Reconstructive Surgery. St. Louis: Mosby; 1998. p. 260–9. 3. Nasr AM, Haik BG, Fleming JC, Al-Hussain HM, Karcioglu ZA. Penetrating orbital injury with organic foreign bodies. Ophthalmology 1999;106:523–32. 4. Finkelstein M, Legmann A, Rubin PA. Projectile metallic foreign bodies in the orbit: a retrospective study of epidemiologic factors, management, and outcomes. Ophthalmology 1997;104:96–103. 5. Callahan AB, Yoon MK. Intraorbital foreign bodies: retrospective chart review and review of literature. Int Ophthalmol Clin 2013;53:157–65. 6. Shelsta HN, Bilyk JR, Rubin PA, Penne RB, Carrasco JR. Wooden intraorbital foreign body injuries: clinical characteristics and outcomes of 23 patients. Ophthal Plast Reconstr Surg 2010;26:238–44. 7. Fulcher TP, McNab AA, Sullivan TJ. Clinical features and management of intraorbital foreign bodies. Ophthalmology 2002;109:494–500. 8. Glatt HJ, Custer PL, Barrett L, Sartor K. Magnetic resonance imaging and computed tomography in a model of wooden foreign bodies in the orbit. Ophthal Plast Reconstr Surg 1990;6:108–14. 9. McNab AA, Satchi K. Orbital foreign bodies and penetrating orbital injuries. In: Black EH, Nesi FA, Calvano CJ, Gladstone GJ, Levine MR, editors. Smith and Nesi’s Ophthalmic Plastic and Reconstructive Surgery. 3rd ed. New York: Springer; 2012. p. 297–307.

10. Wallace JS. Projectiles. In: Chemical Analysis of Firearms, Ammunition, and Gunshot Residue. Boca Raton, FL, USA: CRC Press, Taylor&Francis Group; 2008. p. 67–90. 11. Jacobs NA, Morgan LH. On the management of retained airgun pellets: a survey of 11 orbital cases. Br J Ophthalmol 1988;72:97–100. 12. Moazeni M, Mohammad Alibeigi F, Sayadi M, Poorya Mofrad E, Kheiri S, Darvishi M. The Serum Lead level in Patients With Retained Lead Pellets. Arch Trauma Res 2014;3:18950. 13. Nguyen A, Schaider JJ, Manzanares M, Hanaki R, Rydman RJ, Bokhari F. Elevation of blood lead levels in emergency department patients with extra-articular retained missiles. J Trauma 2005;58:289–99. 14. Farrell SE, Vandevander P, Schoffstall JM, Lee DC. Blood lead levels in emergency department patients with retained lead bullets and shrapnel. Acad Emerg Med 1999;6:208–12. 15. McQuirter JL, Rothenberg SJ, Dinkins GA, Kondrashov V, Manalo M, Todd AC. Change in blood lead concentration up to 1 year after a gunshot wound with a retained bullet. Am J Epidemiol 2004;159:683–92. 16. Schaumberg DA, Mendes F, Balaram M, Dana MR, Sparrow D, Hu H. Accumulated lead exposure and risk of age-related cataract in men. JAMA 2004;292:2750–4. 17. Magos L. Lead poisoning from retained lead projectiles. A critical review of case reports. Hum Exp Toxicol 1994;13:735–42. 18. Orcutt JC. Orbital foreign bodies. In: Linberg JV, editor. Oculoplastic and Orbital Emergencies. Norwalk: Appleton&Lange; 1990. p. 183–97. 19. Cho RI, Kahana A, Patel B, Sivak-Callcott J, Buerger DE, Durairaj VD, et al. Intraoperative fluoroscopy-guided removal of orbital foreign bodies. Ophthal Plast Reconstr Surg 2009;25:215–8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İntraorbital yabancı cisimler: Klinik özellikleri ve cerrahi çıkartım sonuçları Dr. Ayşe Dolar Bilge, Dr. Hakan Yılmaz, Dr. Bülent Yazıcı, Dr. Faisal Naqadan Uludağ Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, Bursa

AMAÇ: Orbitaiçi yabancı cisim nedeniyle ameliyat edilen hastaların klinik özellikleri ve tedavi sonuçları değerlendirildi. GEREÇ VE YÖNTEM: On yıllık bir dönemde orbitaiçi yabancı cisim nedeniyle ameliyat edilen 24 hastanın tıbbi dosyası gözden geçirildi. BULGULAR: Yirmi hasta (%83) erkek, dört hasta (%17) kadındı (ortalama yaş, 28 yıl; veri aralığı: 4–69 yıl ). On hasta (%42) travmayı izleyen 48 saat içinde, yedi hasta (%29) üç gün–bir ay içinde ve yedi hasta (%29) bir aydan sonra başvurdu. Yabancı cisim 19 hastada (%79) inorganik, beş hastada (%21) organikti. Yabancı cisme eşlik eden majör oküler morbiditeler, orbital sellülit (n=5), travmatik optik nöropati (n=3), göz perforasyonu (n=2) ve rektus kası kopmasıydı (n=2). Tüm hastalarda yabancı cisim tam olarak çıkartıldı. Ortalama izlem süresi 26 aydı (veri aralığı: 1 ay–10 yıl). TARTIŞMA: Orbitaiçi yabancı cisimler sıklıkla inorganik ve metaliktir; genç erkeklerde daha sık görülür. Orbital sellülit organik yabancı cisimler için tipik sayılmakla birlikte, lakrimal kese ve paranazal sinüsleri perfore eden metalik yabancı cisimlere bağlı olarak da görülebilir. Orbitaiçi yabancı cisimler, modern orbita cerrahisi yöntemleriyle güvenli bir biçimde çıkartılabilir. Anahtar sözcükler: Cerrahi tedavi; orbitaiçi yabancı cisim; orbitotomi. Ulus Travma Acil Cerrahi Derg 2016;22(5):432–436

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ORIGIN A L A R T IC L E

Traumatic wound dehiscence after penetrating keratoplasty Özlem Barut Selver, M.D., Melis Palamar, M.D., Sait Eğrilmez, M.D., Ayşe Yağcı, M.D. Department of Ophthalmology, Ege University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: The aim of this study was to evaluate risks and consequences of traumatic wound dehiscence after penetrating keratoplasty (PK). METHODS: Data regarding 34 eyes of 34 patients who were treated for traumatic wound dehiscence after PK between 1995 and 2014 were studied. Patient records were reviewed for type and time of insult, corrected distance visual acuity (CDVA), clinical presentation signs, operative method, and outcome. RESULTS: The interval between PK and trauma ranged from 1 month to 100 months, with median of 14 months. Median age at trauma was 31.5 years (range: 5–81 years). Wound dehiscence occurred at donor-recipient interface in all patients. In 58.8% of patients, extent of dehiscence was ≥6 clock hours. Most frequent type of trauma was blunt trauma by hand/finger (35.2%). Median CDVA before and just after trauma were 0.5 logMAR (range: 0.1–3.0 logMAR) and 3.0 logMAR (range: 0.7–3.0 logMAR), respectively. Wound dehiscence was managed with primary wound closure in all patients. Most frequent additional surgical procedure was anterior vitrectomy (26.4%). Anatomical globe loss occurred in 2 patients. Median CDVA was 0.7 logMAR (range: 0.1–3.0 logMAR) at final visit. Most common complication after primary suturation was graft failure (23.5%). Graft remained clear in 67.6% of patients. CONCLUSION: Traumatic wound dehiscence is one of the potentially devastating postoperative complications that can occur following PK. Prognosis depends on existence and severity of additional anterior/posterior segment damage. In order to prevent this catastrophic condition, patients should be warned against ocular trauma after undergoing PK. Keywords: Keratoplasty; ocular trauma; wound dehiscence.

INTRODUCTION One possible and potentially devastating postoperative complication of penetrating keratoplasty (PK), the standard full thickness corneal transplantation technique, is wound dehiscence secondary to trauma.[1] Surgical wound after PK makes cornea more vulnerable to trauma than intact cornea due to decreased strength of graft-host interface.[2,3]

Our department, which has more than 20 years of experience, maintains a large corneal transplantation database. This study retrospectively analyzed incidence, predisposing factors, graft survival, and visual outcome of traumatic wound dehiscence following PK to compare these data and comment on results in the literature.

Incidence of traumatic wound dehiscence after PK has been reported as between 0.6% and 5.8%.[1,4–10] This complication generally occurs within first 2 years after PK, and may lead to delayed visual rehabilitation and increased risk of corneal graft edema and rejection.[4,6,11–14]

MATERIALS AND METHODS

Address for correspondence: Melis Palamar, M.D. Ege Üniversitesi Hastanesi Göz Hastalıkları Anabilim Dalı, Bornova, İzmir, Turkey Tel: +90 232 - 388 14 69 E-mail: melispalamar@hotmail.com Qucik Response Code

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Retrospective data analysis of patients who had corneal wound dehiscence after PK between 1995 and 2014 was performed. Records of patients were reviewed for age, gender, PK indication, type and time of insult, suture presence, accompanying anterior and posterior segment damage, corrected distance visual acuity (CDVA) (as measured with Snellen chart), operative methods, and surgical outcome. Statistical analysis was performed using SPSS software for Windows version 15.0 (SPSS Inc.; Chicago, Illinois, USA) and Microsoft Office Excel (Microsoft Corp.; Redmond, Washington, USA). Shapiro-Wilk test was performed to test normality of data. Statistical analyses were done using frequency tables, nonparametric tests, and logistic regression analyses. A value of p<0.05 was accepted as statistically significant. 437


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RESULTS Incidence of graft dehiscence was 2.6% (34 eyes) among 1300 PK eyes. Male to female ratio was 1.6:1. Most frequent primary PK indication was keratoconus (26.4%). Other common indications were perforation sequel (23.5%) and pseudophakic bullous keratopathy (PBK) (14.7%). The interval between PK and trauma ranged from 1 month to 100 months, with median of 14 months. Median age at time of trauma was 31.5 years (range: 5–81 years). Number of patients under age of 18 was 10 (29.4%). Wound dehiscence occurred at donor-recipient interface in all patients, and 70.5% of graft dehiscences occurred in postoperative 18 months. In most eyes (58.8%), extent of wound dehiscence was ≥6 clock hours. Most frequent type of trauma was minor blunt trauma with hand or finger (35.2%). Other causes of trauma were major blunt trauma, falling, and intentional assault. Prior to trauma, 17 eyes were phakic, 15 eyes were pseudophakic, and 2 eyes were aphakic. Seventeen (50%) eyes had either crystalline lens/intraocular lens dislocation or expulsion upon impact of trauma. Seven phakic and 5 pseudophakic patients (35.2%) had lens expulsion, 1 phakic and 4 pseudophakic patients (14.7%) had lens dislocation (Fig. 1a, b). Iris or vitreous prolapse was detected in 10 eyes (29.4%) (Fig. 2a, b). At time of trauma sutures were present in 22 (64.7%) eyes (Fig. 3). Eight (75%) of 12 eyes without sutures had graft dehiscence within the first 6 months of suture removal. According to logistic regression analysis, presence of sutures and amount of dehiscence were not related (p>0.05). Median CDVA before and right after trauma were 0.5 logMAR (range: 0.1–3.0 logMAR) and 3.0 logMAR (range: 0.7–3.0 logMAR), respectively (p<0.05). Graft dehiscence was managed with primary wound closure in all eyes. Most frequent additional surgical procedure was anterior vitrectomy (29.4%). Posterior segment damage was noted as suprachoroidal hemorrhage (1 patient), macular hemorrhage (1 patient), or retinal detachment (3 patients). Anatomical globe loss occurred in 2 eyes of these 5 patients (1 suprachoroidal hemorrhage patient and 1 retinal detachment patient who also had endophthalmitis afterward). Two retinal detachment patients had a final CDVA of 3.0 logMAR and 1 retinal detachment patient had a final CDVA of 1.0 logMAR. Median CDVA was 0.7 logMAR (range: 0.1–3.0 logMAR) at final visit. Regression analysis was performed to identify predictors of visual acuity loss such as gender, age, time interval between trauma and keratoplasty, suture presentation, dehiscence amount, and lens status. None of the factors were found to be related (p>0.05). Most common complication after primary suturation was graft failure (23.5%). Mean follow up period was 24.9±21.0 months (range: 6–110 months). Graft was clear in 67.6% of patients at final visit. 438

(a)

(b)

Figure 1. (a) Traumatic wound dehiscence caused by finger trauma in a 24-year-old female patient: intraocular lens dislocation from superior graft-host interface, (b) anterior segment appearance after primary suturation.

(a)

(b)

Figure 2. (a) Traumatic wound dehiscence caused by hand trauma in a 70-year-old male patient: iris and vitreous prolapses, (b) anterior segment appearance after primary suturation.

Figure 3. Traumatic wound dehiscence caused by finger trauma in a 63-year-old male patient. Graft dehiscence occurred 4 months after keratoplasty surgery while sutures were present.

DISCUSSION Corneal wound integrity depends on corneal sutures during the first few weeks after surgery. In sutured limbal wounds, reorganization of collagen is required for wound site to regain tensile strength.[11,15] In several studies it has been reported that corneal scar tissue at graft–host interface never recovers strength of normal corneal tissue.[4,16,17] Factors that impair Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


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corneal wound healing and cause wound weakness at grafthost interface after PK include avascular characteristics of cornea, use of non-inflammatory suture material, increased intraocular pressure, and prolonged steroid treatment. For this reason, wound dehiscence after trauma commonly occurs at graft-host junction.[2–4,7,9,10,16] In the present study, all graft dehiscences occurred at graft-host interface, a finding consistent with the literature. In this case series, incidence of graft dehiscence was 2.6% (34 eyes) among 1300 PK eyes, which is also consistent with the literature.[1,4–10] Incidence was reported to be 1.5% in our previous case series consisting of 6 eyes in 398 PK eyes.[18] The first year -- and especially the first month -- is reported to be the most vulnerable period for traumatic wound dehiscence after PK. Risk progressively decreases over next 18 months. [10,11,19] Suture removal weakens wound integrity and risk for wound dehiscence increases significantly.[10] In the present series, 70.5% of graft dehiscences occurred in postoperative 18 months, and 23.5% of graft dehiscence took place within the first 6 months of suture removal. Some authors report that grafts with intact sutures tend to have a smaller degree of dehiscence, but we did not find such a relationship in this case series. Most common indications for PK among patients who developed wound dehiscence were keratoconus and PBK. In the present study, the most common indication was keratoconus (26.4%), which is consistent with the literature.[20,21] The next most common indications were perforation sequel (23.5%) and PBK (14.7%). Anterior or posterior segment damage such as iris prolapse; crystalline lens or intraocular lens extrusion; vitreous loss; corneal endothelium damage, which can cause graft failure; choroidal hemorrhage; and total disruption of intraocular contents may accompany wound dehiscence at time of trauma.[22] In the present series, percentage of iris or vitreous prolapse was (29.4%). Crystalline lens or intraocular lens extrusion was positive in 35.9% of patients. Incidence of lens extrusion has been reported to be 25% to 100% in several studies, and present result is consistent with the literature. [4,6,7,16] Graft failure was detected in 23.5% of patients. Primary determinant of final visual acuity is force of trauma and status of posterior segment.[23] Posterior segment involvement (5 patients) in present series was instances of suprachoroidal hemorrhage, macular hemorrhage, and retinal detachment. Two of these patients had anatomical globe loss and 3 had a final CDVA of 1.0 logMAR or worse. Even if graft appears to be edematous or opaque, immediate wound repair in traumatic wound dehiscence after PK is recommended.[16,17] General anesthesia is a requirement for these traumatic patients, as any blink or blepharospasm movement could cause expulsive hemorrhage.[24] Graft dehiscence was managed with primary wound closure under general anesthesia for all patients in current study. Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

Clear corneal graft percentage after traumatic wound dehiscence was reported to be 20% to 100% in several studies. [7,25] Consistent with the literature, 67.6% of traumatic wound dehiscence patients with preserved globe anatomy in present study had clear grafts. Principal limitation to this study was retrospective format. Records that were not designed for the study and an absence of data on potential confounding factors are the principle disadvantages of retrospective format. In conclusion, even years after surgery, traumatic corneal graft dehiscence is one of the most devastating complications that can occur following PK. Patients should be warned that eyes that had PK will always be vulnerable to injury. For high-risk patients, such as young males, who made up a large proportion of current study (61%); children, who comprise nearly 30% of our patients; people who work with sharp objects, etc., eye shields or goggles are recommended for protection after grafting and just after suture removal. Conflict of interest: None declared.

REFERENCES 1. Bowman RJ, Yorston D, Aitchison TC, McIntyre B, Kirkness CM. Traumatic wound rupture after penetrating keratoplasty in Africa. Br J Ophthalmol 1999;83:530–4. 2. Farley MK, Pettit TH. Traumatic wound dehiscence after penetrating keratoplasty. Am J Ophthalmol 1987;104:44–9. 3. Raber IM, Arentsen JJ, Laibson PR. Traumatic wound dehiscence after penetrating keratoplasty. Arch Ophthalmol 1980;98:1407–9. 4. Agrawal V, Wagh M, Krishnamachary M, Rao GN, Gupta S. Traumatic wound dehiscence after penetrating keratoplasty. Cornea 1995;14:601–3. 5. Elder MJ, Stack RR. Globe rupture following penetrating keratoplasty: how often, why, and what can we do to prevent it? Cornea 2004;23:776– 80. 6. Rehany U, Rumelt S. Ocular trauma following penetrating keratoplasty: incidence, outcome, and postoperative recommendations. Arch Ophthalmol 1998;116:1282–6. 7. Tseng SH, Lin SC, Chen FK. Traumatic wound dehiscence after penetrating keratoplasty: clinical features and outcome in 21 cases. Cornea 1999;18:553,8. 8. Kartal B, Kandemir B, Set T, Kugu S, Keles S, Ceylan E, et al. Traumatic wound dehiscence after penetrating keratoplasty. Ulus Travma Acil Cerrahi Derg 2014;20:181–8. 9. Rohrbach JM, Weidle EG, Steuhl KP, Meilinger S, Pleyer U. Traumatic wound dehiscence after penetrating keratoplasty. Acta Ophthalmol Scand 1996;74:501–5. 10. Lam FC, Rahman MQ, Ramaesh K. Traumatic wound dehiscence after penetrating keratoplasty-a cause for concern. Eye (Lond) 2007;21:1146– 50. 11. Gasset AR, Dohlman CH. The tensile strength of corneal wounds. Arch Ophthalmol 1968;79:595-602. 12. Perry HD, Donnenfeld ED. Expulsive choroidal hemorrhage following suture removal after penetrating keratoplasty. Am J Ophthalmol 1988;106:99–100.

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Barut Selver et al. Traumatic wound dehiscence after penetrating keratoplasty 13. Brown SI, Tragakis MP. Wound dehiscence with keratoplasty: complication of the continuous-suture technique. Am J Ophthalmol 1971;72:115–6. 14. Binder PS, Abel R Jr, Polack FM, Kaufman HE. Keratoplasty wound separations. Am J Ophthalmol 1975;80:109–15. 15. Gliedman ML, Karlson KE. Wound healing and wound strength of sutured limbal wounds. Am J Ophthalmol 1955;39:859–66. 16. Topping TM, Stark WJ, Maumenee E, Kenyon KR. Traumatic wound dehiscence following penetrating keratoplasty. Br J Ophthalmol 1982;66:174–8. 17. Pettinelli DJ, Starr CE, Stark WJ. Late traumatic corneal wound dehiscence after penetrating keratoplasty. Arch Ophthalmol 2005;123:853–6. 18. Egrilmez S, Uzunel UD, Yagci A. Ocular Trauma Following Keratoplasty. MN Ophthalmology 2004;11:200–4. 19. Elder MJ, Stack RR. Globe rupture following penetrating keratoplasty: how often, why, and what can we do to prevent it? Cornea 2004;23:776–80.

20. Nagra PK, Hammersmith KM, Rapuano CJ, Laibson PR, Cohen EJ. Wound dehiscence after penetrating keratoplasty. Cornea 2006;25:132– 5. 21. Cosar CB, Sridhar MS, Cohen EJ, Held EL, Alvim Pde T, Rapuano CJ, et al. Indications for penetrating keratoplasty and associated procedures, 1996-2000. Cornea 2002;21:148–51. 22. Oshry T, Lifihitz T. Traumatic wound dehiscence after corneal graft. Ophthalmic Surg Lasers 2001;32:470–3. 23. Das S, Whiting M, Taylor HR. Corneal wound dehiscence after penetrating keratoplasty. Cornea 2007;26:526–9. 24. Kaslow O, Gollapudy S. Anesthetic considerations for ocular and maxillofacial trauma. In: Varon AJ, Smith CE, eds. Essentials of Trauma Anesthesia. Cambridge, UK: Cambridge University Press 2012. p. 198–219. 25. Foroutan AR, Gheibi GH, Joshaghani M, Ahadian A, Foroutan P. Traumatic wound dehiscence and lens extrusion after penetrating keratoplasty. Cornea 2009;28:1097–9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Penetran keratoplasti sonrası travmatik yara ayrılması Dr. Özlem Barut Selver, Dr. Melis Palamar, Dr. Sait Eğrilmez, Dr. Ayşe Yağcı Ege Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, İzmir

AMAÇ: Bu çalışmanın amacı penetran keratoplasti sonrası oluşan travmatik yara ayrılmasının risklerini ve olası sonuçlarını değerlendirmektir. GEREÇ VE YÖNTEM: Çalışmaya kliniğimizde 1995–2014 yılları arasında penetran keratoplasti sonrası travmatik yara ayrılması gelişen 34 hastanın 34 gözü dahil edilmiştir. Hastaların kayıtları, travmanın tipi ve zamanı, en iyi düzeltilmiş görme keskinliği (EİDGK), başvuru anındaki bulgular, uygulanan cerrahi girişim ve sonuçları açısından incelendi. BULGULAR: Penetran keratoplasti cerrahisi ve travma arasında geçen süre bir ay ile 100 ay arasında değişmekle beraber median 14 aydı. Travma sırasındaki median yaş, 31.5 (5-81) yıldı. Tüm hastalarda yara ayrılması, donör-alıcı ara yüzünde meydana gelmişti. Hastaların %58.8’inde ayrılmanın büyüklüğü, altı saat kadranı veya daha genişti. En sık travma, parmak veya elle olan künt travmaydı (%35.2). En iyi düzeltilmiş görme keskinliği median değeri, travma öncesinde 0.5 logMAR (0.1–3.0), travmadan hemen sonraki muayenede ise 3.0 logMAR (0.7–3.0) idi. Yara ayrılması, tüm hastalarda primer sütürasyon ile tamir edildi. En sık uygulanan ilave cerrahi prosedür, ön vitrektomiydi (%26.4). İki hastada anatomik glob kaybı meydana geldi. Son vizitte, EİDGK median değeri 0.7 logMAR (0.1–3.0) idi. Primer sütürasyon sonrası en sık rastlanan komplikasyon greft yetmezliğiydi (%23.5). Hastaların %67.6’sında greft saydamdı. TARTIŞMA: Travmatik yara ayrılması, penetran keratoplasti sonrası ortaya çıkabilen en yıkıcı komplikasyonlardandır. Prognoz, eşlik eden ön ve arka segment hasarlanmasına bağlıdır. Bu kötü durumdan korunmak amacıyla penetran kornea nakli geçiren hastalar, cerrahi sonrası olası göz travmalarına karşı uyarılmalıdır. Anahtar sözcükler: Keratoplasti; oküler travma; yara ayrılması. Ulus Travma Acil Cerrahi Derg 2016;22(5):437–440

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Management of perforation after endoscopic retrograde cholangiopancreatography Cengiz Tavusbay, M.D.,1 Emrah Alper, M.D.,2 Melek Gökova, M.D.,1 Erdinç Kamer, M.D.,1 Haldun Kar, M.D.,1 Kemal Atahan, M.D.,1 Oğuzhan Özşay, M.D.,1 Özlem Gür, M.D.,1 Necat Cin, M.D.,1 Emir Çapkınoğlu, M.D.,1 Evren Durak, M.D.1 1

Department of General Surgery, İzmir Katip Çelebi University Atatürk Training and Researh Hospital, İzmir-Turkey

2

Department of Gastroenterology, İzmir Katip Çelebi University Atatürk Training and Researh Hospital, İzmir-Turkey

ABSTRACT BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation is an infrequent complication. It is associated with significant morbidity and mortality. The present study is an evaluation of experience with management and outcomes of ERCP-related perforations and a review of relevant literature. METHODS: Between January 2008 and January 2015, a total of 9383 ERCPs were performed in endoscopy unit. A total of 29 perforations (0.33%) were identified and retrospectively reviewed. RESULTS: Of the 29 patients, 18 were female and 11 patients were male, with mean age of 70.5 years (range 33–99 years). According to Stapfer’s classification, the 29 patients with ERCP related perforations included 5 type 1 perforations, 14 type 2 perforations, 7 type 3 perforations, and 3 cases of type 4 perforation. In total, 15 of 29 patients with ERCP perforation were operated on. Nine (60%) of those who underwent surgery were discharged uneventful, but 6 (40%) patients died due to postoperative complications and/or associated comorbidities. Seven (24.1%) of 29 patients had undergone endoscopic treatment and 5 of the 7 were discharged from the hospital without any problems; however, peritonitis occurred in 2 patients whose initial endoscopic treatment failed. The first of these 2 patients underwent surgery and was discharged uneventfully, but second patient, who refused surgery, died due to sepsis. Six patients were successfully treated with conservative management. Surgery could not be performed in the remaining 2 patients, who died of sepsis following peritonitis; 1 refused surgery, the other had sudden cardiopulmonary arrest during induction of general anesthesia. Mean hospital stay was 13.2 days (range: 2–57 days). In all, 9 (31%) patients died during period of the study. CONCLUSION: ERCP-related perforation is uncommon complication, but an extremely serious condition. Early diagnosis and prompt management are most important to reduce associated significant morbidity and mortality rates. The most appropriate treatment course should be determined on case-by-case basis. Keywords: Endoscopic retrograde cholangiopancreatography; endoscopic treatment; perforation.

INTRODUCTION Currently, endoscopic retrograde cholangiopancreatography (ERCP) is widely used for both diagnostic and therapeutic purposes in pancreaticobiliary disorders. ERCP is broadly reAddress for correspondence: Cengiz Tavusbay, M.D. Erzene Mah., Şehit Taha Carım Cad., Özveri Sitesi, No: 3/1, Kat: 3, Bornova, 35050 İzmir, Turkey Tel: +90 232 - 244 44 4 / 2347 E-mail: tavusbay3@gmail.com Qucik Response Code

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garded as a safe procedure; however, ERCP-related complications, such as perforation, bleeding, and pancreatitis can occur, even when procedure is performed by an experienced physician. Since ERCP-related perforation is rare but serious complication accompanied by risk of morbidity and mortality, early diagnosis and treatment are extremely important.[1–3] Accurate diagnosis and effective management of perforation depends on early recognition of clinical features and accurate interpretation of diagnostic imaging. Although some ERCP-related perforations can be successfully managed without surgery, there is currently no clear consensus on optimal treatment modality that can be used in all cases. Several authors have defined different classification schemes for retroperitoneal perforations of ERCP and have suggested a selective management strategy based on type of 441


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injury.[4–6] Additionally, outcome is determined by several factors, including comorbidities, clinical status of patient, size and location of perforation, radiographic imaging findings, and interval between perforation and initiation of therapy. The present study is an assessment of experience with ERCPrelated perforations at a university hospital.

MATERIALS AND METHODS

In the present study, ERCP indications included choledocholithiasis (n=21, with cholangitis in 4 patients and acute pancreatitis in 1 patient), obstructive jaundice with pancreatic mass (n=3), external biliary fistula after surgery for hydatid disease (n=2, 1 patient with cholangitis), papilla Vateri tumor (n=2, 1 patient with cholangitis), and dilated common bile duct (CBD) caused by external compression of metastatic mass (n=1).

A total of 9383 ERCPs were performed in the endoscopy unit of İzmir Katip Çelebi University Atatürk Training and Research Hospital between January 2008 and January 2015. Of these, a total of 29 had related perforation (0.3%), all of which were identified using hospital medical records system. Patient demographics, including age, sex, American Society of Anesthesiologists (ASA) score, and comorbidities (e.g., chronic renal failure [CRF], diabetes mellitus [DM], coronary heart disease [CHD] and malignancy) were assessed. For each of the 29 perforations, indications for ERCP, findings at ERCP, time interval between perforation and surgery, clinical presentation, radiographic findings, management, and outcomes were analyzed. In addition, postoperative data, including complications, length of stay (LOS), secondary interventions, and readmissions within 30 days after discharge were evaluated.

Several different classifications for ERCP-perforations have been reported in the literature.[4,5] In the current study, Stapfer’s classification system was used, which consists of the following types: 1) Lateral or medial duodenal wall perforation, 2) perivaterian injury, 3) distal bile duct injury related to wire/ basket instrumentation, and 4) retroperitoneal air alone.[4]

In endoscopy unit, almost all of the ERCP procedures were performed for therapeutic reasons; all of the patients had primary biliary disease, which was diagnosed with other diagnostic methods, including abdominal computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), abdominal ultrasonography (AUS) or endoluminal ultrasonography (EUS). ERCP indications were established after considering clinical symptoms, history, laboratory results, and radiological imaging results. Endoscopic sphincterotomy was performed in 8123 patients (86.5%) and 1260 patients (13.5%) underwent a pre-cut papillotomy. Standard sphincterotomy was performed by an experienced endoscopist with extensive experience in therapeutic ERCP. Pre-cutting techniques were used only in cases with unsuccessful cannulation.

The present study was approved by the ethics committee of İzmir Katip Çelebi University, Atatürk Training and Research Hospital.

ERCP was performed using therapeutic duodenoscope (TJF 180; Olympus Corp., Tokyo, Japan) by an experienced team using standard technique. In most cases, standard biliary sphincterotomy was used for biliary cannulation. Ionic contrast media diatrizoate (Urografin 76%; Schering AG, Berlin, Germany) was used to view bile and pancreatic duct. Primary team conducted postinterventional observation of all patients for first 24 hours to determine any possible procedurerelated complications. Routine laboratory tests, including complete blood count (CBC), serum amylase, and C-reactive protein (CRP), were performed the first day following ERCP. If there were no complications, patients were discharged within 24 hours post-procedure. 442

All cases were followed by an attendant gastroenterologist, who consulted a surgeon, interventional radiologist, or anesthesiologist, if needed. Immediate emergency surgery is often required if signs and symptoms of peritonitis develop within the first 72 hours. Other conservative medical treatments include withholding of oral intake, hydration, proton pump inhibitory (PPI) therapy, somatostatin (SS), intravenous antibiotics, and serial abdominal examinations with radiological studies.

Descriptive statistics were used to evaluate demographic and clinical characteristics of patients and treatments; correlation analyses were not feasible due to limited number of patients and because many values were unavailable.

RESULTS Demographic and clinical features of patients with ERCPrelated perforation are summarized in Table 1. A total of 29 ERCP-related perforations were identified in this study. Mean age of patients was 70.5 years (range: 33–99 years), and there were 18 female and 11 male patients. It is remarkable to note that 18 patients (62%) were older than 70 years of age at the time of ERCP-related perforation diagnosis. In all, there were 5 type 1 perforations, 14 type 2 perforations, 7 type 3 perforations, and 3 type 4 perforations. As can be easily understood from Table 1, a significant proportion of patients had 1 or more comorbidity. Patients had mean ASA score of 2.28 (range: 1–3). Signs and symptoms of peritonitis developed in 18 patients; mild abdominal pain or discomfort occurred in 11 patients. Abdominal radiography or CT indicated that 15 (51.7%) patients had both free intraperitoneal air and retroperitoneal air, and 14 (48.3%) had only retroperitoneal air (Fig. 1a, b). Five of the 29 patients had Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


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Table 1. Demographic, clinical, and laboratory features of patients with ERCP-related perforation Parameter

Type 1 (n=5)

Type 2 (n=14)

Type 3 (n=7)

Type 4 (n=3)

Total

Age (years)

58–99 (80.2)

37–94 (69.6)

52–88 (77)

33–51 (43.6)

33–99 (70.5)

4

8

6

18 (62%)

2/3

4/10

4/3

1/2

11/18

3

2.29

2.1

1.3

2.28

>70 years Gender (male/female) ASA score (mean)

Comorbidities

Diabetes mellitus

1

3

4

CAD/and/or hypertension

3

9

16

Hashimato’s thyroiditis

4 1

1

Parkinson’s disease

1

1

Alzheimer’s disease

1

1

Rheumatoid arthritis+steroid use

1

1

COPD

1

1

Chronic renal failure

1

1

HBP malignancy

2

2

6

Hepatic hydatid disease

1

2

2

1

Clinical presentation Peritonitis

5

10

3

18

4

4

3

11

2

6

1

15

2

2

1

5

Abdominal pain or discomfort

Fever

Emphysema (subcutaneous and/or

mediastinal emphysema)

Laboratory findings

5

12

6

3

26

Leukocytosis

Elevated C-reactive protein

5

11

5

3

24

3

8

5

1

17

Elevated amylase

ERCP: Endoscopic retrograde cholangiopancreatography; ASA: American Society of Anesthesiologists; COPD: Chronic obstructive pulmonary disease; HBP: Hepatobiliary and pancreatic.

subcutaneous or mediastinal emphysema. While 18 of the 29 patients had obvious signs and symptoms of peritonitis, the other 6 patients had no symptoms of peritonitis, but they had both moderate upper abdominal pain and free intraperitoneal

(a)

air (1 patient) or pneumoretroperitoneum (5 patients). Five patients who were endoscopically treated for ERCP perforation only had mild abdominal pain, which persisted for 1 to 2 days.

(b)

Figure 1. (a) Abdominal CT following perforation shows pneumoperitoneum, pneumoretroperitoneum (blue arrows), and subcutaneous emphysema (red arrow). (b) Coronal abdominal CT scan also shows subcutaneous emphysema in the right inguinal region (blue arrow).

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Tavusbay et al. Management of perforation after endoscopic retrograde cholangiopancreatography

in 1 week), 1 had bile duct stenosis due to tumor, 1 had metastatic hepatoduodenal lymphadenopathy, and 1 patient with Billroth II gastrectomy had duodenal wall perforation. Standard sphincterotomy was performed in 23 patients with ERCP perforation, while pre-cut sphincterotomy was performed in 5 patients. Perforation was detected or suspected in 11 (37.9%) of the 29 patients during ERCP. Six (20.7%) of the 29 cases were diagnosed with perforation within 24 hours of ERCP (mean: 11.3 hours, range: 6–22 hours). The other 12 (41.4%) patients were diagnosed with perforation more than 24 hours after ERCP (mean: 54.4 hours, range: 26–144 hours).

C-reactive protein (CRP) levels were elevated in 26 patients (1.17–37.2 mg/L), 24 patients had leukocytosis (11600– 36400/mm3), and amylase values were elevated in 17 patients (250–3169 IU/L). As illustrated in Table 2, ERCP indications of patients were as follows: choledocholithiasis (n=21, 4 with acute cholangitis, 1 acute pancreatitis), cancer (n=6), and biliary fistula following surgery for hepatic hydatid disease (n=2). Cancers found were: pancreas head (n=2), papilla Vateri tumor (n=2, 1 with acute cholangitis), Klatskin tumor (n=1), extrabiliary tumor compressing biliary system (n=1). Of the 29 patients with ERCP-related perforations, 12 perforations resulted from papillotomy, 12 resulted from inserting a balloon or basket into CBD after papillotomy while stone was being removed, and 5 resulted from lateral duodenal wall perforation due to trauma of duodenoscope. Unexpected technical difficulties were encountered in 12 patients. Of these, 5 patients had duodenal diverticula, 2 had increased fragility due to malignant tumor, 2 had subsequent ERCP (3 times

As can be seen in Table 3, 15 (51.7%) of the 29 patients underwent surgery due to peritonitis following ERCP procedure. Eleven patients underwent exploratory laparotomy and drainage of retroperitoneal and intraperitoneal spaces. Five of these 11 patients had additional surgical procedure (choledocotomy and T-tube drainage in 3 patients, cholecystectomy in 2 patients, and choledocoenterostomy in 1 pa-

Table 2. Data related to indications of ERCP, technical difficulties, type of endoscopic sphincterotomy, and time of diagnosis of perforation ERCP data

Perforation Type Type 1 (n=5)

Type 2 (n=14)

Type 3 (n=7)

Type 4 (n=3)

Total

3 (with 1

12 (with 1

cholangitis)

cholangitis)

4 (with 1 acute

(with 2

21 (with 4 cholangitis,

pancreatitis 2)

cholangitis)

1 acute

1) ERCP indications

Common bile duct stone

pancreatitis)

Cancer (pancreatic, duodenal

or extrabiliary tumor)

2 (with 1

2

cholangitis)

2 (with 1

6 (2 cholangitis)

cholangitis)

Biliary fistula following surgery

for hepatic hydatid disease

1

1

2

2) Technical difficulties (n=12)

Ampullary duodenal diverticulum

2

3

5

Increased mucosal fragility of papilla

1

1

2

Bile duct stenosis due to tumor

and metastatic lymphadenopathy

1

1

2

Billroth II operation

1

1

Subsequent ERCP (3 times in a week)

1

1

2

3) Type of ES Standard

4

Precut

– 4 – 1

10

7

2

23 5

4) Diagnosis time

During ERCP

3

5

2

1

11

Early presentation (<24 hours)

2

2

2

6

Late presentation (>24 hours)

2

7

3

12

ERCP: Endoscopic retrograde cholangiopancreatography; ES: Endoscopic sphincterotomy.

444

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Tavusbay et al. Management of perforation after endoscopic retrograde cholangiopancreatography

Table 3. Data regarding method of management of post-ERCP perforation, hospital stay, and mortality Parameter

Perforation type Type 1 (n=5)

Type 2 (n=14)

9

Type 3 (n=7)

Type 4 (n=3)

Total

I. Treatment modality

A. Surgery

4

2

15

1) Primary repair

2

2

2) Whipple procedure

1

1

3) Cholesystectomy, tube

duodenostomy, pyloric

exclusion, gastrojejunostomy,

Braun anastomosis)

1

1

Surgical drainage of

9 (with Cholecystectomy

retroperitoneal and

in 2, T-tube drainage after

drainage after

peritoneal spaces

choledocotomy in 2,

choledocotomy

choledocoenterostomy in 1)

2 (with T-tube

in 1)

11

B. No surgery for reasons

1

1

1

3

C. Conservative medical

1

2

6

1 (Unsuccessful

4 (3 successful, 1 patient

2

3

treatment

D. Endoscopic treatment

II. Mean hospital stay (days) III. Death

clipping)

underwent surgery)

7 (2 unsuccessful)

15.6 (6–23)

14.6 (2–57)

12 (3–40)

6.6 (2–16)

13.2 (2–57)

3 (60%)

5 (35.7%)

2 (28.5%)

10 (34.4%)

ERCP: Endoscopic retrograde cholangiopancreatography.

tient). Importantly, in 11 of the 15 patients who underwent surgery, perforation site could not be found due to severe inflammation and edema. Two patients underwent primary repair of duodenum. One of these (58 years old) had history of Billroth II operation and type 2 DM. He also had choledocholithiasis with acute cholangitis. Even though diagnosis was made early and surgery was performed immediately, patient died due to uncontrolled severe complications related to anesthesia. The second patient with choledocholithiasis was 99 years old, and also had ampullary duodenal diverticulum. She was still alive at the age of 101 at the time of this report, and did not have any problems related to the surgery. The third patient underwent Whipple procedure because she could not undergo primary repair and because she had malignant tumor of the papilla of Vater. Postoperative course was uneventful, and she was discharged from the hospital in good health. Another patient with choledocholithiasis underwent cholecystectomy, tube duodenostomy, pyloric exclusion, gastrojejunostomy, and Braun anastomosis for peritonitis following ERCP-related perforation; this patient died due to septic complications. The fifth patient in this group had acute abdomen; this patient died due to sepsis 6 days after ERCP despite endoscopic treatment during ERCP procedure (endoscopic clipping). She was admitted to clinic with jaundice, and was given preliminary diagnosis of Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

pancreatic cancer. Although revision operation was offered, she and her family refused the surgery due to her advanced age and multiple comorbidities. In total, 7 patients (24.1%) were endoscopically treated by gastroenterologist (e.g., metal stent placement and/or clipping). Five of these 7 patients were managed conservatively because they had no symptoms of peritonitis and they were discharged without any problems. Peritonitis occurred in 2 patients whose initial endoscopic treatment failed. The first of these patients underwent surgery and was discharged uneventfully, but second patient, who refused surgery, died due to sepsis in first week after ERCP. After perforation diagnosis, 6 of the 29 patients were immediately treated with conservative management for 2-16 days because signs and symptoms of manifest peritonitis did not develop. All of these 6 patients successfully recovered, and were discharged uneventful. Overall, mean hospital stay was 13.2 days (range: 2–57 days), and a total of 10 (34.4%) patients died in this study. Seven (46.6%) of the 15 patients who underwent surgery died due to septic and/or other complications during early postoperative period. 445


Tavusbay et al. Management of perforation after endoscopic retrograde cholangiopancreatography

DISCUSSION ERCP-related perforation is rare but serious complication. Incidence of perforation has been reported to range between 0.01% and 2.1%.[1–3] In the current series, rate of ERCP-related perforation was 0.3%, which is similar to the literature for age range of 33 to 99 years. Most authors have reported that major risk factors for ERCP-related perforations include sphincter of Oddi dysfunction (SOD), Billroth II anatomy, intramural injection of contrast, prolonged duration of procedure, biliary stricture dilation, experience of endoscopist, biliary stricture dilation, and other anatomical anomalies.[1–3] It has been indicated that perforations caused by therapeutic ERCP procedures are often diagnosed in the late period.[4,7,8] Considering results of our current study, it is thought that most common risk factors are history of Billroth II operation, dilatation of biliary stricture due to malignant or benign causes, anatomical anomalies (such as duodenal diverticula), fragile papilla Vateri, old age, difficult cannulation, pre-cut sphincterotomy and long procedure duration. Highrisk and/or elderly patients should only undergo endoscopy performed by very experienced endoscopist with careful and meticulous attention to reduce the risk of perforation. Delayed diagnosis and surgical intervention may result in significant morbidity and mortality due to sepsis and multiple organ failure. Further, if surgery is delayed too long, exploration of retroperitoneal space is extremely difficult. Inflammation may be so severe that separation of normal anatomy is difficult or even impossible; perforation site often cannot be found in these patients. There is much debate surrounding treatment of ERCP-related perforations, and treatment algorithm for ERCP-related perforations changes based on factors such as patient age and clinical status, comorbidities, time of certain diagnosis, size and location of perforation, time of surgery, and radiological findings. One of the most difficult issues for clinicians is early detection of patients who will require surgery. This decision requires multidisciplinary approach by gastroenterologist, surgeon, and anesthesiologist. Majority of authors have reported that radiological results, amount of retroperitoneal air, and/or pneumomediastinum are not correlated with clinical course; these data represent the amount of air used during ERCP and do not provide indication for surgery.[9–11] Recently, it has been reported that most retroperitoneal perforations could be treated with conservative medical therapy; some authors have concluded that guidewire perforations are generally benign and do not require surgery.[12–14] Certain patients are likely to improve under conservative management, which includes hospitalization, intestinal rest, and administration of intravenous fluids and antibiotics to limit peritonitis and allow perforation to seal. However, patients should undergo careful observation with frequent and repeated abdominal exams for early diagnosis of peritonitis. If patient 446

is clinically stable and abdominal symptoms do not indicate deterioration due to peritoneal signs, patient can be treated non-surgically. Zuckerman et al. reported that early diagnosis of periampullary perforation and aggressive medical treatment led to clinical improvement without operative intervention in 86% of patients.[15] In the current study, 6 patients were treated medically; all of them had repeat CT scans, all of which revealed decreasing amounts of air. Their laboratory findings and clinical course gradually improved without the need for surgery or any additional treatment methods. Ultimately, our experience suggests that certain patients with periampullary perforations can recover with this conservative treatment in early phase and avoid surgery. While some authors have proposed early operations for all ERCP-related peritoneal perforations, recent studies have demonstrated the possibility of endoscopic perforation closure with endoscopic methods and they are being used with increasing frequency.[14,16–18] It has been reported that peritoneal perforations can be sutured under endoscope.[17,19] Successful closure with endoscopy in conservatively managed patients can reduce the fasting period, duration of intravenous antibiotic administration, and hospital stay. Moreover, it can improve patient quality of life and reduce medical costs. In the present study, 5 patients were successfully treated with endoscopic methods, while endoscopic treatment was unsuccessful in 2 patients. One of these 2 patients had duodenal perforation, and was treated with endoscopic clips. In this patient, both diagnosis and treatment were made during ERCP procedure. However, this treatment failed, and patient developed peritonitis. Some authors have advocated a selective management algorithm for ERCP-related perforations.[7,9–12] Wu et al. concluded that periampullary perforations should be treated aggressively with broad spectrum antibiotics, fasting, and aggressive endoscopic bile diversion (biliary stent or nasobiliary tube) from site of perforation.[9] The authors went on to say that surgery is required if retroperitoneal fluid is seen on abdominal CT or if clinical picture worsens in 24 hours. In addition, the authors recommended surgery for all type 1 perforations (duodenal perforations). Kim et al. proposed a new classification based on the instrument that caused the perforation: type 1 injuries are caused by endoscopic tip or insertion tube, type 2 injuries occur due to sphincterotomy knives or cannulation catheters, and type 3 injuries are caused by guidewires after cannulation of the ampulla. The authors suggested that type 1 injuries require immediate surgical management after ERCP or immediate endoscopic closure during ERCP. In addition, they stated that surgical treatment should be considered in type 2 injuries with dirty fluid collection in the intra- and retroperitoneal area on CT; if there is no fluid collection, conservative treatment is possible.[17] Husain et al. reported that 33% (7/21) of patients showed extraluminal retroperitoneal Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Tavusbay et al. Management of perforation after endoscopic retrograde cholangiopancreatography

air following ERCP; they concluded that it was not clinically significant.[20] Stapfer et al. suggested that retroperitoneal air alone requires no additional treatment or further work-up if abdominal examinations are normal and there is no evidence or suspicion of contrast extravasation. Three of the patients in the current study had retroperitoneal air after ERCP via radiological findings, but symptoms were mild. In addition, vital signs and laboratory values of these 3 patients were also normal, and there was no fluid collection in retroperitoneal or intra-abdominal cavity. We successfully treated these patients with conservative management. Although very useful and different algorithms for the treatment of ERCP-related perforations have been suggested by several authors, it is the opinion of the authors of the present study that treatment modality is best decided on case-by-case basis, and must be individualized. Mutignani et al. reported that fibrin glue was used to treat ERCP-related perforation.[21] Seibert et al. successfully used endoscopic clipping to treat duodenal perforation that occurred during an endoscopic US examination.[19] Based on these data, we suggest that, if possible, immediate closure by endoscopic methods should be used for ERCP-related perforation, followed by conservative management. However, in these instances, patient should be closely observed by specialists. If patient does not improve and rapidly deteriorates developing signs of intraabdominal sepsis within the first 48 hours despite conservative treatment, surgery should be considered immediately. Perforations detected in late period should be treated with conservative medical management in addition to surgical draining of fluid exudation or by percutaneous puncturing drainage; this can prevent or treat infection.[22,23]

mortality rate was 34.4% (10/29 patients). Although other results were similar to those in the literature, mortality ratio is comparatively higher. It is suggested that primary main causes for higher mortality in our study were delayed diagnosis, old age, high ASA score and perforation type. In conclusion, ERCP-related perforation is an uncommon complication, but one that can cause extremely serious conditions. Early diagnosis and prompt management are important to decrease morbidity and mortality. Patients with ERCP-related perforations should be closely monitored in an intensive care unit (ICU) by gastroenterologist, anesthesiologist, and surgeon; this team should decide whether to proceed with surgery. The most appropriate treatment course should be decided on case-by-case basis. Although immediate surgical closure has been standard treatment for ERCPrelated perforation of duodenal wall, currently, endoscopic interventions using clips, endoloops, glue injection, and newly developed devices can be used in selected patients. It is believed that endoscopic treatment may develop further and that there will be several alternative methods to surgery in the near future. Conflict of interest: None declared.

REFERENCES 1. Loperfido S, Angelini G, Benedetti G, Chilovi F, Costan F, De Berardinis F, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998;48:1–10. 2. Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001;96:417–23.

As indicated, various treatment modalities were used in the current study, ranging from conservative techniques to surgical methods. Morever, patients underwent several different surgical procedures, including primary closure, T-tube choledochostomy, duodenal diverticulization, and Whipple operation. Authors believe that characteristics of each individual patient should determine most appropriate treatment modality and/or surgical method.

3. Enns R, Eloubeidi MA, Mergener K, Jowell PS, Branch MS, Pappas TM, et al. ERCP-related perforations: risk factors and management. Endoscopy 2002;34:293–8.

Mortality rate of ERCP-related perforations varies between 4.2% and 37%, and delay in treatment of more than 24 hours after perforation can result in a doubling of mortality.[24–26] In the current study, 4 of the patients who were diagnosed in the late period (42, 72, 72, and 88 hours) died due to uncontrollable sepsis; 1 patient had rheumatoid arthritis for 25 years and had been prescribed steroid drugs. Another of these patients was 85 years old and was diagnosed 42 hours after ERCP procedure; she had multiple comorbidities (CRF, hypertension, atherosclerotic heart disease, ejection fraction [EF] 65%, type 2 DM and chronic anemia). The other deceased patient with type 3 perforation had peritonitis; he died just prior to surgery due to sepsis and other comorbidities during induction of anesthetic agents. In present study,

6. Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF, Martin D, et al. Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study. Endoscopy 2007;39:793–801.

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4. Stapfer M, Selby RR, Stain SC, Katkhouda N, Parekh D, Jabbour N, et al. Management of duodenal perforation after endoscopic retrograde cholangiopancreatography and sphincterotomy. Ann Surg 2000;232:191–8. 5. Howard TJ, Tan T, Lehman GA, Sherman S, Madura JA, Fogel E, et al. Classification and management of perforations complicating endoscopic sphincterotomy. Surgery 1999;126:658–65.

7. Fatima J, Baron TH, Topazian MD, Houghton SG, Iqbal CW, Ott BJ, et al. Pancreaticobiliary and duodenal perforations after periampullary endoscopic procedures: diagnosis and management. Arch Surg 2007;142:448–55. 8. Lee TH, Han JH, Park SH. Endoscopic treatments of endoscopic retrograde cholangiopancreatography-related duodenal perforations. Clin Endosc 2013;46:522–8. 9. Wu HM, Dixon E, May GR, Sutherland FR. Management of perforation after endoscopic retrograde cholangiopancreatography (ERCP): a population-based review. HPB (Oxford) 2006;8:393–9. 10. Lai CH, Lau WY. Management of endoscopic retrograde cholangiopancreatography-related perforation. Surgeon 2008;6:45–8.

447


Tavusbay et al. Management of perforation after endoscopic retrograde cholangiopancreatography 11. Li G, Chen Y, Zhou X, Lv N. Early management experience of perforation after ERCP. Gastroenterol Res Pract 2012;2012:657418. 12. Alexiou K, Sakellaridis T, Sikalias N, Karanikas I, Economou N, Antsaklis G. Subcutaneous emphysema, pneumomediastinum and pneumoperitoneum after unsuccessful ERCP: a case report. Cases J 2009;2:120. 13. Fujii L, Lau A, Fleischer DE, Harrison ME. Successful Nonsurgical Treatment of Pneumomediastinum, Pneumothorax, Pneumoperitoneum, Pneumoretroperitoneum, and Subcutaneous Emphysema following ERCP. Gastroenterol Res Pract 2010;2010:289135. 14. Lee TH, Bang BW, Jeong JI, Kim HG, Jeong S, Park SM, et al. Primary endoscopic approximation suture under cap-assisted endoscopy of an ERCP-induced duodenal perforation. World J Gastroenterol 2010;16:2305–10. 15. Standards of Practice Committee, Zuckerman MJ, Shen B, Harrison ME 3rd, Baron TH, Adler DG, Davila RE, et al. Informed consent for GI endoscopy. Gastrointest Endosc 2007;66:213–8. 16. Nakagawa Y, Nagai T, Soma W, Okawara H, Nakashima H, Tasaki T, et al. Endoscopic closure of a large ERCP-related lateral duodenal perforation by using endoloops and endoclips. Gastrointest Endosc 2010;72:216–7. 17. Kim BS, Kim IG, Ryu BY, Kim JH, Yoo KS, Baik GH, et al. Management of endoscopic retrograde cholangiopancreatography-related perforations. J Korean Surg Soc 2011;81:195–204. 18. Park WY, Cho KB, Kim ES, Park KS. A case of ampullary perforation treated with a temporally covered metal stent. Clin Endosc 2012;45:177–80.

19. Seibert DG. Seibert DG. Use of an endoscopic clipping device to repair a duodenal perforation. Endoscopy 2003;35:189. 20. Husain S, Garmager K, McPhee MS, Jacob KM, Fisher JK, Helzberg JH. The significance of retroperitoneal air following endoscopic sphincterotomy. Gastrointest Endosc1995;41:400. 21. Mutignani M, Iacopini F, Dokas S, Larghi A, Familiari P, Tringali A, et al. Successful endoscopic closure of a lateral duodenal perforation at ERCP with fibrin glue. Gastrointest Endosc 2006;63:725–7. 22. Krishna RP, Singh RK, Behari A, Kumar A, Saxena R, Kapoor VK. Post-endoscopic retrograde cholangiopancreatography perforation managed by surgery or percutaneous drainage. Surg Today 2011;41:660–6. 23. Morgan KA, Fontenot BB, Ruddy JM, Mickey S, Adams DB. Endoscopic retrograde cholangiopancreatography gut perforations: when to wait! When to operate! Am Surg 2009;75:477–84. 24. Ercan M, Bostanci EB, Dalgic T, Karaman K, Ozogul YB, Ozer I, et al. Surgical outcome of patients with perforation after endoscopic retrograde cholangiopancreatography. J Laparoendosc Adv Surg Tech A 2012;22:371–7. 25. Alfieri S, Rosa F, Cina C, Tortorelli AP, Tringali A, Perri V, et al. Management of duodeno-pancreato-biliary perforations after ERCP: outcomes from an Italian tertiary referral center. Surg Endosc 2013;27:2005–12. 26. Miller R, Zbar A, Klein Y, Buyeviz V, Melzer E, Mosenkis BN, et al. Perforations following endoscopic retrograde cholangiopancreatography: a single institution experience and surgical recommendations. Am J Surg 2013;206:180–6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Endoskopik retrograd kolanjiopankreatikografiye bağlı perforasyonların tedavisi Dr. Cengiz Tavusbay,1 Dr. Emrah Alper,2 Dr. Melek Gökova,1 Dr. Erdinç Kamer,1 Dr. Haldun Kar,1 Dr. Kemal Atahan,1 Dr. Oğuzhan Özşay,1 Dr. Özlem Gür,1 Dr. Necat Cin,1 Dr. Emir Çapkınoğlu,1 Dr. Evren Durak1 1 2

İzmir Katip Çelebi Üniversitesi Tıp Fakültesi, Atatürk Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir İzmir Katip Çelebi Üniversitesi Tıp Fakültesi, Atatürk Eğitim ve Araştırma Hastanesi, Gastroenterolojii Kliniği, İzmir

AMAÇ: Endoskopik retrograd kolanjiopankreatikografiye (ERKP) bağlı perforasyonlar az görülmelerine karşılık yüksek morbidite ve mortalite oranlarına sahiptir. Bu çalışmada ERKP’ye bağlı perforasyonların tedavisi ve sonuçlarımıza ait tecrübelerimizi değerlendirmeyi ve ilgili literatürün gözden geçirilmesini amaçladık. GEREÇ VE YÖNTEM: Ocak 2008 ve Ocak 2015 yılları arasında İzmir Katip Çelebi Üniversitesi, Atatürk Eğitim ve Araştırma Hastanesi Endoskopi Ünitesi’nde toplam 9383 ERKP işlemi yapıldı. Bu hastaların 29’unda (%0.33), ERKP’ye bağlı perforasyon tespit edildi ve bu hastalara ait veriler geriye dönük olarak değerlendirildi. BULGULAR: Yirmi dokuz hastanın 18’i kadın, 11’i erkek hasta olup, ortalama yaş 70.5 (33–99 yaşlar arası) idi. Stapfer sınıflandırmasına göre 5 hastada tip 1, 14 hastada tip 2, 7 hastada tip 3 ve 3 hastada da tip 4 perforasyon saptandı. Toplam olarak, 15 hastaya cerrahi tedavi uygulandı; bunlardan 9’u (%60) sorunsuz olarak taburcu edilirken, 6 (%40) hasta ameliyat sonrası komplikasyonlardan dolayı öldü. Yirmi dokuz hastanın 7’sinde (%24.1) ise başlangıçta endoskopik tedavi uygulandı ve bu hastalardan beşi sorunsuz olarak taburcu edildi. Ancak endoskopik tedavi iki hastada başarısız oldu. Peritonit gelişen bu 2 hastadan ilki, cerrahi tedavi sonrası sorunsuz olarak taburcu edildi. Cerrahi tedaviyi kabul etmeyen diğer hasta ise sepsis nedeni ile öldü. Altı hasta konservatif tıbbi tedavi ile başarılı bir şekilde tedavi edildi. Peritonit sonrası gelişen sepsis nedeniyle hayatını kaybeden 2 hastadan ilkinde hasta ve yakınlarının cerrahi tedaviyi reddetmesi nedeniyle, diğer hastada ise, anestezinin indüksiyon evresinde ani gelişen kardiyopulmoner arrest sonucu cerrahi tedavi yapılamadı. Çalışmamızda ortalama hastanede kalma süresi 13.2 gün (2–57), ölen hasta sayısı ise dokuz (%31) idi. TARTIŞMA: Endoskopik retrograd kolanjiopankreatikografiye bağlı perforasyonlar nadir görülmesine karşılık yüksek mortalite oranları yol açabilmesi nedeni ile son derece önemli bir klinik durumdur. Erken tanı ve tedavi mortalite ve morbidite oranlarının azaltılmasında çok önemlidir. En uygun tedavi yöntemi, hastanın bireysel özellikleri ve klinik durumu göz önünde bulundurularak verilmelidir. Anahtar sözcükler: Endoskopik retrograd kolanjiopankreatikografi (ERKP); endoskopik tedavi; perforasyon. Ulus Travma Acil Cerrahi Derg 2016;22(5):441–448

448

doi: 10.5505/tjtes.2016.42247

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ORIGIN A L A R T IC L E

Evaluation of patients diagnosed with acute blunt aortic injury and their bedside plain chest radiography in the emergency department: A retrospective study Funda Karbek Akarca, M.D.,1 Tanzer Korkmaz, M.D.,2 Celal Çınar, M.D.,3 Elif Dilek Çakal, M.D.,1 Murat Ersel, M.D.1 1

Department of Emergency Medicine, Ege University Faculty of Medicine, İzmir-Turkey

2

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

3

Department of Radiology, Ege University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: The purpose of our study was to retrospectively evaluate traumatic aortic transection patients and their bedside plain chest radiographs for signs of aortic injury. METHODS: Emergency department (ED) patients from a 5-year period with traumatic aortic transection who were over 18 years of age were included in the study. Demographic characteristics, mechanism of trauma, Revised Trauma Score, Glasgow Coma Score, vital signs, physical exam findings, laboratory parameters, length of stay in the ED, and patient outcomes were documented. Bedside plain chest radiograph images were interpreted by 2 emergency medicine specialists and 1 radiologist. RESULTS: Thirty patients, mean age 45.87±16.14 years (70% male), were enrolled. Most common trauma mechanism was motor vehicle accident (53.3%). Agreement rates between emergency medicine specialists and radiologist were found to be “excellent” and “substantial” in identifying mediastinal widening and multiple left sided rib fractures; and “fair” in identifying widened paraspinal line, and transthoracic vertebral fractures. CONCLUSION: Though not completely reliable, bedside plain chest radiographs and physical examination findings may be useful in detecting aortic injury during primary survey when the patient is unstable and cannot be sent for chest computerized tomography. Appropriate further imaging studies should be carried out as appropriate based on patient’s hemodynamic status. Keywords: Aortic transection; imaging; reliability; trauma.

INTRODUCTION Thoracic aortic injuries are responsible for a considerable portion of the deaths related to trauma. Though mostly due to blunt trauma mechanisms, thoracic aortic injuries may also result from penetrating and crushing types of trauma.[1] Penetrating injuries are easily identified; however, diagnosis of blunt trauma may easily be missed. Traumatic energy arising from an impact is usually distributed throughout the entire Address for correspondence: Funda Karbek Akarca, M.D. Ege Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir, Turkey Tel: +90 232 - 390 23 18 E-mail: fundakarbek@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):449–456 doi: 10.5505/tjtes.2016.58524 Copyright 2016 TJTES

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mediastinal area. Crushing of the thoracic aorta between the sternum and the vertebral structures causes a sudden significant increase in intraluminal pressure. The proximal descending aorta is at greatest risk from shearing forces of sudden deceleration because it is fixed between the subclavian artery and ligamentum arteriosum.[2] Acute blunt traumatic aortic injury (ABTAI) was first defined by an anatomist in 1557 to describe a victim who fell off a horse.[3] Aortic transection is a rare lesion among major vessel injuries resulting from thoracic trauma. Incidence was calculated to be 0.3% in a series of pedestrian accident victims (5838 cases), 0.1% in a series of victims of fall from height (1163 cases), and 1.4% in a series of pelvic fractures (1450 cases).[4] It has been reported that 80% of these patients do not survive to the emergency department (ED).[1,4] If the adventitial layer of the aorta remains intact due to incomplete laceration of the ligamentum arteriosum, or if mediastinal hematoma develops, the patient may survive long enough to receive urgent definitive treatment.[5] Timely diagnosis and treatment of aortic injury 449


Karbek Akarca et al. Evaluation of acute blunt injury patients in ER with radiologic findings

is crucial for the survival of a multitrauma patient admitted to the ED. History, physical exam, and bedside chest x-ray (CXR) provide useful clues leading to the diagnosis. However, one-third of patients with aortic injury due to blunt trauma do not show any external signs at physical examination.[6] It is also mentioned in the literature that even though bedside CXR may reveal many signs pointing to major vessel injury, most of these findings lack sensitivity and specificity.[5,7] Chest computerized tomography (CCT) is a frequently used imaging modality for trauma patients in the ED, with sensitivity and specificity rates nearing 100%.[4,5] The aim of the present study was to retrospectively evaluate patients sent to the ED with ABTAI and compare the correlation between emergency medicine specialists and radiologists in interpreting bedside CXR images for possible aortic injury.

MATERIALS AND METHODS Study Design This retrospective cross-sectional study was performed in the ED of Ege University Hospital. University ethics committee approval was obtained prior to data collection. National laws and the World Medical Association Second Declaration of Helsinki were followed to protect patient rights and honor.

Study Setting and Population All patients diagnosed as traumatic aortic transection in the ED of Ege University hospital between January 1, 2011 and December 31, 2015 were retrospectively evaluated. Study population was composed of patients with International Statistical Classification of Diseases and Related Health Problems (ICD)-10 code I71. Patients older than 18 years of age with traumatic aortic transection who had sufficient medical data were included in the study. Patients with penetrating trauma were excluded.

Study Protocol Demographic values, trauma mechanism (fall from height, motorcycle accident, motor vehicle accident, pedestrian accident), Revised Trauma Score (RTS), Glasgow Coma Score (GCS), and vital signs (blood pressure [BP], heart rate [HR], respiratory rate, oxygen saturation) on arrival, physical examination findings (crackles, thoracic skin crepitation), laboratory parameters (white blood cell [WBC] count, hemoglobin [Hb], blood urea nitrogen [BUN], creatinine, liver function tests), length of stay in the ED, and clinical outcomes (admission, discharge, exitus) were recorded. Localization of aortic transection was recorded (aortic isthmus within 2 cm of the origin of the left subclavian artery, descending aorta, aortic arc or aortic isthmus).[8] Surgical treatment methods used were noted (thoracic endovascular aortic repair [TEVAR], endovascular aortic repair [EVAR]). Aspartate aminotransferase (AST) levels <35 U/L and alanine aminotransferase (ALT) levels <45 U/L were considered normal. BUN, cre450

atinine, WBC and Hb levels were measured as mg/dL, mg/ dL, mm3 and g/dL respectively. The first bedside CXR and CCT images were digitally documented. CXR images were interpreted by 2 emergency medicine specialists and 1 radiologist, noting if several parameters were present or absent. Reviewing physicians were emergency medicine specialists with advanced degree and more than 10 years of experience in their specialty. Reviewers’ interpretations were compared to reports of official radiologist, who had more than 5 years of experience in interventional radiology. Radiologist’s interpretation was accepted as authoritative in bedside CXR image evaluation. The following parameters were examined as aortic transection criteria on CXR:[7,9] 1. Mediastinal widening: More than 8 cm when supine (at the level of the left subclavian artery origin) on anteroposterior view of the chest or mediastinum to chest width ratio of >0.25.[9,10] 2. Downward displacement of the left mainstem bronchus: >140° from trachea 3. Indistinct or abnormal aortic contour 4. Deviation of trachea: To the right of the T3 or T4 spinous processes 5. Left apical capping 6. First and/or second rib fractures 7. Multiple left-sided rib fractures 8. Widened paraspinal line 9. Transthoracic vertebral fracture 10. Lung contusion 11. Left side hemothorax The following parameters were examined for aortic transection on CCT images taken with third-generation CT scanner (Discovery CT 750 HD scanner; GE Healthcare, Little Chalfont, UK): Left first and/or second rib and left others rib fractures, scapula, sternum, clavicula and transthoracic vertebral fracture, left and any side hemothorax, pneumothorax, lung contusion, and mediastinal hematoma.

Statistical Analysis SPSS software (version 17.0; SPSS Inc., Chicago, IL, USA) software was used for the statistical analyses. For measurement data conforming to normal distribution, arithmetic mean and standard deviation were calculated, and for data not conforming to normal distribution, median and 95% confidence intervals (CI) were obtained. For categorical data obtained by counting, the number and percentage were used.

Reliability Assessment The kappa statistic was determined for each adverse effect to document inter-rater reliability and was reported as an overall mean with standard deviation. Kappa statistic of <0.00 was considered poor, 0.00–0.20 was slight, 0.21–0.40 was fair, 0.41–0.60 was moderate, 0.61–0.80 was substantial, and Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Karbek Akarca et al. Evaluation of acute blunt injury patients in ER with radiologic findings

16

16

Total Male Female

12 10 8 6

6 4

3 1

0

Vehicle accident

5

2

Pedestrian

5

5

1 Motorcycle

0 Fall

Figure 1. Distribution of patient age and gender according to trauma mechanism.

0.81–1.00 was excellent agreement between physician raters. P-value of less than 0.05 was considered significant.

RESULTS Between January 1, 2011 and December 31, 2015, 30911 of 605971 ED patients were trauma patients. Of 501 patients who were recorded as ICD code I71, 30 (5.98%) had aortic injury. The mean age of patients with ABTAI was 45.87±16.14 years (range: 19–75 years), men predominated (n=21), and 30% (n=99) were 55 years and older. The most common trauma mechanism was motor vehicle collision. One 21-yearold male committed suicide by jumping from 2nd floor, and a 19-year-old female committed suicide by jumping in front of a train. Distribution of patient age and gender according to

trauma mechanism is provided in Figure 1. RTS upon arrival, and hemodynamic and laboratory parameters are shown in Table 1. RTS was 8 in 21 (70%) cases, 7 in 5 (16.7%) cases, and 6 in 2 (6.7%) cases. GCS was 15 in 24 (60%) cases, 13 in 1 case, and 14 in 3 cases. GCS of 2 patients were undetermined. Arterial systolic BP was <100 mmHg in 9 cases and arterial diastolic BP was <60 mmHg in 12 cases. All cases with low systolic and diastolic arterial BP were tachycardic (pulse >100/min). Laboratory parameters revealed 24 cases (80%) with elevated level of AST, 20 cases (66.7%) showed elevated level of ALT, 22 cases (73.3%) had high WBC level and 2 cases (6.7%) had low WBC count. Physical exam recordings revealed crackles in 3 cases (10%) and skin crepitation in 5 cases (16.7%). CCT scan results revealed 8 cases (26.7%) with subcutaneous emphysema. Of the CXRs, 29 (96.7%) were found in the archives. Figure 2 shows examples of pathological ABTAI CXR images. Evaluation of bedside CXR by the radiologist and inter-rater reliability evaluation results are shown in Table 2. Agreement rates between emergency medicine specialists and radiologists were found to be excellent and substantial in identification of mediastinal widening and multiple left-sided rib fractures, and fair in identification of widened paraspinal line and transthoracic vertebral fractures. CCT results of all 30 cases were obtained and are shown in Table 3 and Figure 3. Of all cases, 40% had left lung contusion, 30% had mediastinal hematoma, and 33% had left first and/or second rib fracture. The most common localization for transection was the isthmus region of the aorta (Figure 4). Average length of stay in the ED was 21.95±29.95 hours

Table 1. Distribution of Glasgow Coma Score, Revised Trauma Score, vital signs, and laboratory parameters Mean or median

Range or 95%CI Lower-upper bound

Revised Trauma Score

7.6±0.61

Glascow Coma Score*

15±0.08 14.6–15.0

6–8

Vital signs

Arterial systolic blood pressure (mmHg)

121.67±23.88

73–170

Arterial diastolic blood pressure (mmHg)

72.18±22.33

43–122

Respiratory rate (min)

27.85±7.02

18–40

Pulse rate (min)

StO2 (%)

107.44±22.24

78–160

93.29±4.20

85–99%

Laboratory parameters

Aspartate aminotransferase* (U/L) 93.00±42.98

75.71–251.80

Alanine aminotransferase (U/L) 51.00±32.69

52.32–186.29

White blood cells (mm3)

*

Blood urea nitrogen (mg/dL)

Creatinine (mg/dL)

15918.44±7422.09 1209.00–3431.00 38.89±13.18

19.00–74.00

0.98±0.26

0.59–1.43

Hemoglobin (mg/dL)

12.80±2.33

8.00–16.70

Hematocrit (%)

37.98±6.20

25.00–50.00

*Data not conforming to normal distribution.

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Karbek Akarca et al. Evaluation of acute blunt injury patients in ER with radiologic findings

(a)

(b)

Figure 2. (a) Downward displacement of the left mainstem bronchus on chest x-ray and mediastinal widening, (b) white arrow indicates deviation of trachea; black arrow illustrates indistinct or abnormal aortic contour; magnifying glass shows first and second rib fractures; asterisks mark subcutaneous emphysema.

(range: 1–137 hours), mean length of stay was 10.55±5.46 hours (CI%: 10.78–33.12).

(a)

(d)

The outcomes were as follows: 14 cases (46.7%) were admitted to cardiovascular surgery ward, 6 cases (20%) were ad-

(b)

(e)

(c)

(f)

Figure 3. (a) Anteroposterior supine chest radiograph illustrating normal mediastinal widening in this patient, (b) contrast-enhanced axial computed tomography image of the chest with arrow indicating intimal flaps associated with traumatic aortic injury, (c) contrast-enhanced sagittal reformatted computed tomography image showing segmental transection (arrow), (d) CT scan with 3-dimensional reformation showing aortic transection (arrow), (e) oblique catheter angiogram image (arrow) from aortic isthmus, (f) computed tomography performed following endograft deployment.

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Karbek Akarca et al. Evaluation of acute blunt injury patients in ER with radiologic findings

Table 2. Radiologistâ&#x20AC;&#x2122;s evaluation of the bedside chest radiograph and indication of inter-rater reliability Rad Rad/EMS1 Rad/EMS2 EMS1/EMS2 evaluation

n (%)

k* SE k* SE k* SE

Widened mediastinum

18 (60.0)

0.707

0.136

0.854

0.100

0.854

0.100

Downward displacement of the left mainstem bronchus

4 (13.3)

0.669

0.171

0.606

0.205

0.583

0.184

Indistinct or abnormal aortic contour

14 (46.7)

0.726

0.122

0.794

0.110

0.784

0.118

Left apical capping

7 (23.3)

0.551

0.177

0.589

0.160

0.840

0.108

First and/or second rib fractures

7 (23.3)

0.793

0.138

0.793

0.138

0.760

0.162

Multiple left-sided rib fractures

9 (3.0)

0.854

0.100

0.707

0.136

0.854

0.100

Lung contusion

7 (23.3)

0.847

0.104

0.765

0.127

0.765

0.127

Left side hemothorax

3 (10.0)

0.722

0.128

0.862

0.094

0.861

0.094

Deviation of trachea

1 (3.3)

0.651

0.322

0.651

0.322

0.463

0.321

Widened paraspinal stripe

6 (20.0)

0.392

0.134

0.392

0.134

0.862

0.094

Transthoracic vertebral fracture

2 (6.7)

0.346

0.291

0.266

0.258

0.838

0.157

EMS1-2: Emergency medicine specialists; k*: Kappa; rad: Radiologist; SE: Standard error. p value: Rad/EMS1 and Rad/EMS2 statistically insignificant in transthoracic vertebral fracture (p=0.291, p=0.124 respectively) and other data statistically significant (p<0.05).

DISCUSSION

Table 3. Findings on computed tomography of the chest Findings on computerized tomography of chest

n

%

Left first and/or second rib fracture

10

33.3

Left other rib fracture

11

36.7

Bilateral first and/or second rib fracture

2

6.7

Bilateral other rib fracture

5

16.7

Scapula fracture

4

13.3

Sternum fracture

2

6.7

Clavicula fracture

7

23.3

Transthoracic vertebral fracture

1

3.3

Any side hemothorax

13

43.3

Left side hemothorax

5

16.7

Any side pneumothorax

23

66.7

Left side pneumothorax

10

33.3

Lung contusion

21

70.0

Mediastinal hematoma

9

30.0

mitted to anesthesiology and reanimation intensive care unit (ICU), 3 cases (10%) were admitted to general surgery ward, 3 cases (10%) were admitted to other wards, and 3 cases (10%) were discharged from the ED due to regression of findings. During follow up, 5 of the admitted cases were transferred from wards to ICU, where they became exitus (at day 2, 7, 21, 25, 46). Three of these patients had vital signs of BP <100/60 mmHg and HR>100 bpm. Ten patients (33.3%) underwent TEVAR surgery and 1 patient (3.3%) underwent EVAR surgery; remaining patients were managed conservatively. Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

ABTAI is common in multitrauma patients and delay in its diagnosis causes significant mortality. In a case series where autopsies of 420 accidental deaths were evaluated, in nearly 10% of cases, the cause of death was found to be aortic injury.[9] Other studies have found that motor vehicle accidents are responsible for 68â&#x20AC;&#x201C;95% of deaths due to aortic injury, and male patients are more common.[8,11] Mosquera et al. reported mean age to be 41.33 years, and 26.3% of patients were over 55 years of age.[12] Present study results correlated with literature findings. %10 Ascending + isthmus aorta (3 case)

%7 Descending aorta (2 case)

%17 Aortic arch (5 case)

%67 Aortic isthmus (20 case)

Figure 4. Patient injury locations.

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Karbek Akarca et al. Evaluation of acute blunt injury patients in ER with radiologic findings

Rupture of the transected aorta in blunt thoracic trauma causes intrathoracic bleeding, which leads to resistant hypotension and a significant risk for mortality if not repaired in time.[5,12] Generally, these patients do not possess significant physical examination findings; however, they are hemodynamically unstable, and in case of high suspicion, CXR provides clues for diagnosis.[5,6] Blackmore et al. described 7 risk factors related to aortic injury including age >50 years, BP <90 mmHg and thoracic trauma.[13] In a multicenter study, Mosquera et al. (82 aortic injuries from years 1980–2010) defined a traumatic aortic injury score (TRAINS) that included these criteria: widened mediastinum, hypotension, hemothorax, contusion, left scapular fracture.[12] Mosquera et al. found mean RTS to be 5.98 and 34.2% of cases had GCS <9.[12] Present study cases had similar characteristics; however, mean RTS and GCS were higher in this study group. O’Conor stated that according to different studies, if aortic arch, descending aorta, aortopulmonary window, trachea, and left paraspinal space are normal, aortic rupture is 92% unlikely; and if nasogastric tube deviation does not exist and right paratracheal contour is clear, aortic rupture is 98% unlikely. It was said that if aortic arch and contour are normal and nasogastric tube or trachea deviation does not exist, aortic rupture can be ruled out.[9] On bedside CXR, mediastinal widening has high sensitivity (81–100%) and low specificity (34–60%).[9,14] According to ATLS guidelines, false positive and false negative findings seldom (1–13%) exist in CXR images. [14,15] In the present study, 40% (n=12) of cases did not exhibit mediastinal widening. It should be kept in mind that although existence of mediastinal widening is significant, aortic injury cannot be ruled out in cases without mediastinal widening. In case of mediastinal hematoma, existence of indistinct aortic contour has high sensitivity but low specificity (53% to 100%, 21% to 55%, respectively) at predicting aortic injury.[14] In the current study, only 9 of the 14 cases with indistinct aortic contour on bedside CXR had mediastinal hematoma on CCT images. This difference may arise from the fact that most patients had the CXR taken in supine position using portable imaging equipment, rendering interpretation of CXR findings difficult because of poorer technical quality. It has been stated in previous literature that depression of the left mainstem bronchus, deviation of the trachea and nasogastric tube to the right of the T3 or T4 spinous processes in CXR images may indicate aortic injury.[14] In the present study, of the 9 cases with mediastinal hematoma on CCT, only 4 cases had depression of the left mainstem bronchus and only 1 had deviation of the trachea on CXR. The first 3 ribs are protected by scapula, humerus, clavicle and their muscle groups. Injury to these bones and soft tissues may result in lung and major vessel injuries, increasing mortality by 35%.[5] In a study, only 4 of 50 cases with first and/or second rib fractures were accompanied by aortic injury (incidence 8%). It was emphasized that rib fractures did not have negative predictive value for aortic injury. Mediastinal widening, trachea deviation, and loss of aortic contour are underlined as strong determinants for 454

using advanced imaging techniques to look for aortic injury. [16] In this study, according to the radiologist reports, left first and/or second rib fractures were seen in 7 cases (23.3%) on CXR and 10 cases (33.3%) on CCT. The soft tissue barrier around these ribs may be the reason bedside CXR images are blurry and harder to interpret. A study found that CCT is more sensitive than CXR in diagnosing rib fractures. Bone scintigraphy spotted 186, CCT spotted 62, and CXR identified 128 rib fractures.[17] During secondary survey, patients with thoracic trauma should be evaluated for subcutaneous emphysema and fractures of rib, sternum, and scapula. Though not acutely lethal, these injuries may gradually lead to death. [5,12] In the present study, 4 cases had scapula fracture and 2 cases had sternum fracture. Subcutaneous emphysema may arise from direct trauma or esophageal and airway trauma. In these cases, it should be kept in mind that positive pressure ventilation may lead to tension pneumothorax.[5] In hemodynamically unstable patients who need emergent intervention, physical examination and bedside CXR help spot serious injuries. In hemodynamically stable patients, CCT is an excellent tool for diagnosing aortic injury.[14] It is not advised to use CCT routinely in all blunt traumas, but in selected cases. [18] After CCT, no further imaging is required for ABTAI and surgical endovascular repair should be done as soon as possible.[19] Several reports have documented CCT as being more sensitive than conventional radiography at detecting blunt thoracic injuries.[5,18,20] In the 1980s and 1990s, CT was used together with angiography, but today, particularly multidetector-row CT has become the primary diagnostic tool.[14] Allen and Blostein showed that CT was more efficient at detecting lung contusions than simultaneously taken CXR. It was stated that the contusion area determined with CT was 2-3 times larger than the area determined with CXR.[21] Similarly, in the present study, 21 cases had contusion on CCT while only 7 cases had contusion on CXR. Considering these findings, it can be stated that bedside CXR is not completely reliable in determining the seriousness of the injury. Mediastinal hematoma spotted on CCT is of critical importance; however, it may be of venous origin as well as aortic origin.[14] In the present study, all of the patients had aortic injury; however, 30% (n=9) had mediastinal hematoma. In ABTAI, aortic tears are mostly seen in the isthmic area (79%-96%), especially within 2 cm of the subclavian artery.[4,8,22] In the current study, 77% (n=23) of cases had the injury in the isthmic area. In the literature, it is reported that 80–90% of cases with aortic injury died at the accident site, and 20% lasted longer than 1 hour. Of those, 30% died in the first 6 hours, and 49% died within 24 hours. Of the remaining cases, 72% died within 8 days, and 90% of survivors died within the first 4 months.[23] In a study of 24 cases, 15 received surgical repair; 2 (7%) cases died in the acute period (in the ED and operating room) and 2 died in the long-term conservative period.[8] In a comparison of a study conducted by the American Association for the Surgery of Trauma completed in 1997 (AAST1) and a similar study completed 10 years later (AAST2), mortality in patients who underwent open repair and EVAR was found to be 31% Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Karbek Akarca et al. Evaluation of acute blunt injury patients in ER with radiologic findings

in AAST1 and 13% in AAST2.[20] It is stated in the guidelines that 50% of the cases who survive to the hospital die within the first 24 hours. There are studies in the literature stating that 60% to 80% of cases that reach the hospital and receiving definitive therapy survive.[1,6,24] In the present study, 5 patients (16.6%) who received surgical repair (TEVAR, EVAR) died. None of our cases were open surgical repair. Though it is hard to comment upon long-term deaths since this study did not have long-term follow-up, it is possible to note that short-term mortality has gradually decreased along with the advancement of surgical techniques. Bedside CXR still has critical importance even though advancements in technology have rendered CT more available. For this reason, it is important to have a consensus in CXR interpretation to plan definitive treatment. In a study evaluating CXR images for mediastinal widening and aortic injury, Ho et al. stated that inter-rater reliability between 7 different radiologists was moderate (kappa=0.49). Ho et al. suggested that this might stem from probable deficiencies in medical education, and they concluded that mediastinal widening should no longer be used a predictor for aortic injury. [25] In the present study, inter-rater reliability between the radiologist and the emergency medicine specialists was better (kappa=0.70–0.84), but this might be related to the fact that the interpreters were not blind in our study. In conclusion, fast diagnosis and definitive treatment directly affect mortality and morbidity in cases of ABTAI. Primary survey physical examination findings and CXR images may provide clues in running the first resuscitation. For secondary survey, hemodynamic stability of the patient and trauma mechanism may lead in determining appropriate further imaging techniques.

Limitations This study does have limitations. First, it was conducted at a single institution and it includes the limitations inherent in any retrospective study. Second, because bedside CXR does not fulfill optimal requirements for an ideal CXR, image quality may be impaired, leading to false-positive results. Third, radiographs were presented to readers in an artificial research setting. For this reason, problems in recording or shooting may have affected image quality. Fourth, none of the readers were blind to the CXR; however, we believe that this limitation is acceptable, since our main aim in this study was not to define inter-rater reliability of diagnostic criteria. Conflict of interest: None declared.

REFERENCES 1. Fox N, Schwartz D, Salazar JH, Haut ER, Dahm P, Black JH, et al. Evaluation and management of blunt traumatic aortic injury: a practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg 2015;78:136–46.

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2. Chen MY, Miller PR, McLaughlin CA, Kortesis BG, Kavanagh PV, Dyer RB. The trend of using computed tomography in the detection of acute thoracic aortic and branch vessel injury after blunt thoracic trauma: single-center experience over 13 years. J Trauma 2004;56:783–5. 3. Mattox KL, Wall MJ Jr. Historical review of blunt injury to the thoracic aorta. Chest Surg Clin N Am 2000;10:167–82. 4. Demetriades D. Blunt thoracic aortic injuries: crossing the Rubicon. J Am Coll Surg 2012;214:247–59. 5. Ramenofsky M. Reconsidering the role of photoperiod in relation to effects of precipitation and food availability on spring departure of a migratory bird. Proc Biol Sci 2012;279:15–7. 6. Steenburg SD, Ravenel JG, Ikonomidis JS, Schönholz C, Reeves S. Acute traumatic aortic injury: imaging evaluation and management. Radiology 2008;248:748–62. 7. Woodring JH. The normal mediastinum in blunt traumatic rupture of the thoracic aorta and brachiocephalic arteries. J Emerg Med 1990;8:467–76. 8. Steenburg SD, Ravenel JG. Acute traumatic thoracic aortic injuries: experience with 64-MDCT. AJR Am J Roentgenol 2008;191:1564–9. 9. O’Conor CE. Diagnosing traumatic rupture of the thoracic aorta in the emergency department. Emerg Med J 2004;21:414–9. 10. Seltzer SE, D’Orsi C, Kirshner R, DeWeese JA. Traumatic aortic rupture: plain radiographic findings. AJR Am J Roentgenol 1981;137:1011– 4. 11. Burkhart HM, Gomez GA, Jacobson LE, Pless JE, Broadie TA. Fatal blunt aortic injuries: a review of 242 autopsy cases. J Trauma 2001;50:113–5. 12. Mosquera VX, Marini M, Muñiz J, Asorey-Veiga V, Adrio-Nazar B, Boix R, et al. Traumatic aortic injury score (TRAINS): an easy and simple score for early detection of traumatic aortic injuries in major trauma patients with associated blunt chest trauma. Intensive Care Med 2012;38:1487–96. 13. Blackmore CC, Zweibel A, Mann FA. Determining risk of traumatic aortic injury: how to optimize imaging strategy. AJR Am J Roentgenol 2000;174:343–7. 14. Raptis CA, Hammer MM, Raman KG, Mellnick VM, Bhalla S. Acute traumatic aortic injury: practical considerations for the diagnostic radiologist. J Thorac Imaging 2015;30:202–13. 15. Fabian TC, Richardson JD, Croce MA, Smith JS Jr, Rodman G Jr, Kearney PA, et al. Prospective study of blunt aortic injury: Multicenter Trial of the American Association for the Surgery of Trauma. J Trauma 1997;42:374–80; discussion 380–3. 16. Woodring JH, Fried AM, Hatfield DR, Stevens RK, Todd EP. Fractures of first and second ribs: predictive value for arterial and bronchial injury. AJR Am J Roentgenol 1982;138:211–5. 17. Gunay SEI, Kurkcuoglu IC. The comparison of bone scintigraphy, computerized tomography and direct graphy in early period in blunt thoracic trauma. Tıp Araştırmaları Dergisi 2013;11:4. 18. Blostein PA, Hodgman CG. Computed tomography of the chest in blunt thoracic trauma: results of a prospective study. J Trauma 1997;43:13–8. 19. Scaglione M, Pinto A, Pinto F, Romano L, Ragozzino A, Grassi R. Role of contrast-enhanced helical CT in the evaluation of acute thoracic aortic injuries after blunt chest trauma. Eur Radiol 2001;11:2444–8. 20. Demetriades D, Velmahos GC, Scalea TM, Jurkovich GJ, Karmy-Jones R, Teixeira PG, et al. Diagnosis and treatment of blunt thoracic aortic injuries: changing perspectives. J Trauma 2008;64:1415–9. 21. Allen GS, Cox CS Jr. Pulmonary contusion in children: diagnosis and management. South Med J 1998;91:1099–106. 22. Macura KJ, Corl FM, Fishman EK, Bluemke DA. Pathogenesis in acute aortic syndromes: aortic aneurysm leak and rupture and traumatic aortic

455


Karbek Akarca et al. Evaluation of acute blunt injury patients in ER with radiologic findings transection. AJR Am J Roentgenol 2003;181:303–7. 23. Holmes JH 4th, Bloch RD, Hall RA, Carter YM, Karmy-Jones RC. Natural history of traumatic rupture of the thoracic aorta managed nonoperatively: a longitudinal analysis. Ann Thorac Surg 2002;73:1149–54. 24. Orron DE, Porter DH, Kim D, Tortella B. False-positive aortography

following blunt chest trauma: case report. Cardiovasc Intervent Radiol 1988;11:132–5. 25. Ho RT, Blackmore CC, Bloch RD, Hoffer EK, Mann FA, Stern EJ, et al. Can we rely on mediastinal widening on chest radiography to identify subjects with aortic injury? Emerg Radiol 2002;9:183–7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Acil serviste akut künt travmatik aortik yaralanma tanısı alan olguların geriye dönük incelenmesi ve yatakbaşı akciğer grafi görüntülerinin değerlendirilmesi Dr. Funda Karbek Akarca,1 Dr. Tanzer Korkmaz,2 Dr. Celal Çınar,3 Dr. Elif Dilek Çakal,1 Dr. Murat Ersel1 Ege Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir İzmir Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir 3 Ege Üniversitesi Tıp Fakültesi, Radyoloji Bilim Dalı, İzmir 1 2

AMAÇ: Akut künt travmatik aortik yaralanması ile başvuran olguların geriye dönük olarak incelenmesi ve yatakbaşı akciğer grafisinde muhtemel aortik yaralanmaya ait bulgularının değerlendirilmesi amaçlandı. GEREÇ VE YÖNTEM: Beş yıllık dönemde 18 yaş üstü akut travmatik aort transeksiyonu tanılı hastanın dosyaları geriye dönük olarak incelendi. Demografik özellikleri, olayın niteliği, revise travma skoru, Glaskow koma skalası, vital bulguları, fizik muayene bulguları, biyokimyasal parametreleri, acilde kalış süreleri, olguların takip sonucu ve yatakbaşı çekilen akciğer grafisi iki acil tıp uzmanı ve bir radyolog tarafından değerlendirildi. BULGULAR: Çalışmaya 30 olgu alındı. Yaş ortalaması 45.87±16.14 (%70 erkek) ve en sık nedeni araçiçi trafik kazası (%53.3) idi. Acil tıp uzmanları ve radyolog uyumu mediastinal genişlemesi ve sol seri kot kırıklarında ‘mükemmel-kabul edilebilir’, paraspinal hattın genişlemesi ve torasik vertebra kırığında ‘zayıf ’ olarak tespit edildi. TARTIŞMA: Akut künt travmatik aortik yaralanma primer bakıda fizik muayene ve akciğer grafisi resüsitasyon için fikir verebilir. İkincil bakı için hastanın hemodinamik stabilitesi ve yaralanma mekanizmaları da gözönüne alınarak uygun görüntüleme stratejileri belirlenmelidir. Anahtar sözcükler: Aortik transeksiyon; görüntüleme; travma; uyumluluk. Ulus Travma Acil Cerrahi Derg 2016;22(5):449–456

456

doi: 10.5505/tjtes.2016.58524

Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


ORIGIN A L A R T IC L E

The effect of body mass index on trauma severity and prognosis in trauma patients Hasan Mansur Durgun, M.D.,1 Recep Dursun, M.D.,1 Yılmaz Zengin, M.D.,1 Ayhan Özhasenekler, M.D.,2 Murat Orak, M.D.,1 Mehmet Üstündağ, M.D.,1 Cahfer Güloğlu, M.D.1 1

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

2

Department of Emergency Medicine, Yildirim Beyazit University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: As in the rest of the world, the prevalence of obesity in Turkey has been increasing in recent years and has become a major public health issue. Although many trials have been conducted to study the effects of obesity on internal diseases, there are few studies investigating the effects of obesity on prognosis of trauma patients. The present study analyzed the effects of body mass index (BMI) on trauma severity and prognosis in trauma patients. METHODS: This study was prospectively conducted with trauma patients older than 15 years of age who presented at the Dicle University Faculty of Medicine emergency medicine department trauma unit between June 1, 2013 and May 31, 2014. Patients were grouped into high-energy trauma and low-energy trauma groups based on trauma severity. In addition, 4 groups were made according to BMI value (kg/m2). Group I was defined as BMI <25 (normal weight). Group II patients had BMI of 25–29.9 (overweight). Group III had BMI of 30–34.9 (obese), and Group IV was made up of patients with BMI ≥35 (morbidly obese). RESULTS: Comparison of whole patient population for inter-group differences showed significant differences between rate of head injury, thoracic injury, extremity injury, multitrauma, clinic admission rate, and mortality rate (p<0.001). No significant difference was observed between groups in abdominal injury rate (p=0.347). CONCLUSION: Clinic admission rate, length of intensive care unit stay, mortality rate, multitrauma rate, and injury severity score increased in proportion to greater BMI. Keywords: Body mass index; obesity; trauma severity indices.

INTRODUCTION The prevalence of obesity has recently increased and become a major public health concern. Obese patients are at especially higher risk for certain disorders such as cancer, hypertension, heart disease, diabetes mellitus (DM), hyperlipidemia, insulin resistance, and arthritis. In addition, they also have higher risk of mortality.[1] Numerous studies have demonstrated the relationship between obesity and the above-mentioned disorders. Obesity is directly or indirectly linked to 7 Address for correspondence: Hasan Mansur Durgun, M.D. Dicle Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, 21280 Diyarbakır, Turkey Tel: +90 412 - 248 80 01 / 5208 E-mail: hmdurgun@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):457–465 doi: 10.5505/tjtes.2016.93385 Copyright 2016 TJTES

Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

among the 10 most common causes of death (heart disease, malignancy, stroke, chronic obstructive respiratory disease, DM, influenza, and pneumonia).[2,3] Although the association of obesity with various internal disorders has been widely studied, the number of studies investigating the effect of obesity on prognosis of trauma patients is rather limited. Some studies have demonstrated that obesity is an independent risk factor for mortality in highenergy blunt traumas.[4] Obesity has been identified as a risk factor for adverse outcomes after trauma in adult patients, and mortality and morbidity rates, length of hospital stay, and injury severity score (ISS) have been found higher in obese adolescents with traumatic injury compared to their normalweight counterparts.[5,6] The present study investigated whether or not body mass index (BMI) had an incremental effect on trauma severity in trauma patients, and we sought to answer the following questions: (a) Is there any difference between prognosis, clinical admission, need for intensive care, mortality rate, and dura457


Durgun et al. The effect of body mass index on trauma severity and prognosis in trauma patients

tion of hospital stay between obese or overweight patients and normal-weight patients in high-energy (HET) (e.g., motor vehicle accidents, fall from a height) and low-energy traumas (LET)? (b) Is there a relationship between BMI and ISS score?

MATERIALS AND METHODS This study was prospectively conducted with trauma patients older than 15 years of age who presented to the Dicle University Faculty of Medicine trauma unit in the department of emergency medicine between June 1, 2013 and May 31, 2014. It was approved by the Dicle University medical faculty ethics committee for non-interventional studies. Motor vehicle accidents and falls from a height were included in the HET category, while simple falls (e.g., fall while walking) were considered LET.[7] Firearm injuries, sharp object injuries, simple cuts as a result of assault or accident, and patients younger than 15 years of age were excluded. BMI (kg/m2) values were calculated for all patients; those with insufficient weight and height information were excluded. Participants were clustered into 4 groups according to BMI value: Group I: BMI <25 (normal-weight), Group II: BMI 25–29.9 (overweight), Group III: BMI 30–34.9 (obese), and Group IV: BMI ≥35 (morbidly obese). Demographic characteristics at admission (age, sex, trauma mode, weight, height, chronic disorders, Glasgow Coma Scale (GCS), blood pressure, pulse rate, respiratory rate, injury sites, and ISS score), length of stay in intensive care unit (ICU), therapies applied on hospital admission, discharge reports, and death reports were recorded. Outcomes were compared between BMI groups among HET patients, LET patients, and all trauma patients.

Statistical Analysis Data were analyzed with SPSS statistical software (version 18.0; SPSS Inc., Chicago, IL, USA). Data are presented as mean±SD for continuous variables and as percentage for categorical variables. Data were compared across the 4 BMI groups using chi-square test for categorical variables and analysis of variance (ANOVA) for continuous variables. For univariate analysis, means of continuous variables among BMI groups were compared using multi-group ANOVA with Bonferroni method used for post hoc analysis. P value of <0.05 was considered a statistically significant result. Mortality, hospital admission rate, ICU admission rate, frequency of injury by body region, length of ICU stay, and ISS scores were provided using cross tables. To assess impact of BMI on outcome, multivariate logistic regression analysis was performed with hospital mortality as target variable. Odds ratios with 95% confidence intervals are reported.

RESULTS During the 1-year period of study, a total of 4328 trauma patients presented to the emergency service trauma unit. Of 458

these, 1588 patients with HET and LET formed the study group, and 1398 of those patients had the necessary height and weight data and met the study criteria. Mean BMI of whole patient population was 26.49±4.33 (range: 19–43). In the entire patient population, 42.2% (n=591) were normoweight, 36.7% (n=513) were overweight, 17.1% (n=240) were obese, and 3.8% (n=54) were morbidly obese. The number of male patients was 840 (60.1%), and mean age of the whole patient population was 38.09±18.61 years (range: 15–91 years). Men had a mean age of 35.76±17.85 years, and women had a mean age of 41.61±19.30 years. Patients were studied in 2 groups based on trauma severity: HET and LET. Among the study population, 65.4% (n=915) were subjected to HET, and 34.6% (n=483) to LET. Of the patients who experienced HET, 41.3% (n=378) were normoweight, 39.7% (n=363) were overweight, 14.4% (n=132) were obese, and 4.5% (n=42) were morbidly obese. Of the patients who were exposed to LET, 44.1% (n=213) were normoweight, 31.1% (n=150) were overweight, 22.3% (n=108) were obese, and 2.5% (n=12) were morbidly obese. Comparison of male:female ratio between groups revealed that while male gender predominated in normoweight and overweight patients, female gender predominated in obese patients. There were an equal number of men and women in the morbidly obese group. Analysis of the whole patient population for inter-group differences in rates of injury by body region showed significant differences in frequency of head injury, thoracic injury, extremity injury, and multitrauma (p<0.001). No significant difference was observed between groups in terms of abdominal injury rate (p=0.347). Additionally, analysis of results indicated a significant difference between groups with respect to clinic admission rate and mortality rate (p<0.001), whereas no significant difference was observed in terms of ICU admission rate (p=0.052) (Table 1). Data on inter-group differences in length of ICU stay and ISS scores showed significant differences between mean ISS scores and length of ICU stay (days) of the entire patient population compared to HET and LET groups (p<0.001) (Table 2). When all patients were analyzed as a whole, it was observed that clinic admission rate, length of ICU stay, mortality rate, multitrauma rate, and ISS score increased in proportion to increase in BMI (Table 3). Clinic admission rate was significantly lower in Group I compared to Groups II, III, and IV (p<0.001). Length of ICU stay and mortality rate were higher in both Group III and Group IV (obese groups) compared to both Group I and Group II. ISS scores were higher in Group II, III, and IV than Group I. In the comparison of groups in terms of injury region, no significant difference was observed with respect to the rate of abdominal trauma, although Group IV had a striking increase in trauma rates in all body regions, parUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Durgun et al. The effect of body mass index on trauma severity and prognosis in trauma patients

Table 1. Inter-group differences in type of injury. clinic and intensive care admission rate, and mortality rate Head injury

Group I

Group II

Group III

Group IV

p

n % n % n % n % 291 49.2 249 48.5 105 43.6 39 72.2 <0.001

Thoracic injury 126 21.3 93 18.1 66 27.4 21 38.9 <0.001 Abdominal injury 45 7.6 33 6.4 24 10 3 5.6 0.347 Extremity injury 363 61.4 270 52.6 163 67.6 36 66.7 <0.001 Multitrauma

=192 33 =177 34.5 =114 47.5 =33 61.1 <0.001

Clinical admission

=153

ICU admission

=69 11.7 =78 15.2 =45 18.8 =9 16.7 0.052

Mortality

=6 1 =12 2.3 =9 3.8 =6 11.1 <0.001

25.9

=207

40.4

=99

41.2

=27

50

<0.001

ICU: Intensive care unit;

Table 2. Mean injury severity score and length of intensive care unit stay by group

Group I

Group II

Group III

Group IV

p

Mean±SD Mean±SD Mean±SD Mean±SD

All patients’ mean ISS scores

9.46±11.93

14.93±14.46

59±14.73

16.22±9.51

<0.001

All patients’ length of ICU stay

3.84±2.98

6.12±4.78

10.98±9.98

13.22±7.36

<0.001

HET patients’ mean ISS score

12.63±13.60

18.97±15.21

25.52±14.66

19.29±8.47

<0.001

LET patients’ mean ISS scores

3.82±4.19

5.16±4.61

7.89±7.02

5.50±2.71

<0.001

HET: High-energy trauma; ICU: Intensive care unit; ISS: Injury severity score; LET: Low-energy trauma; SD: Standard deviation.

ticularly the multitrauma rate. Head trauma was more common in Group IV than the other groups; it was more frequent particularly in Group III and Group IV, the obese groups, compared to Group I. Thoracic trauma was more common in Group III and Group IV than in Group I and Group II. No significant difference was observed between groups with regard to rate of abdominal trauma. The rate of extremity trauma was higher in Groups I, III, and IV than in Group II. The multitrauma rate increased as BMI increased, and it was higher in the obese groups., i.e., Group III and Group IV, than in Group I and Group II. Analysis of only patients presenting with HET revealed greater length of ICU stay, mortality rate, ISS score, and multitrauma rate in proportion to increase in BMI (Table 4). The clinic admission rate was higher in Groups II and IV than in Group I, and higher in Group IV than in Group III. Length of ICU stay was greater in Group III and Group IV (the obese groups) than in Group I and Group II. Mortality rate, as was length of ICU stay, was higher in Group III and Group IV than in Group I and Group II. Furthermore, mortality rates of Group II, Group III, and Group IV were higher than that of Group I, and mortality rate of Group IV was higher than that of Group III. ISS scores were significantly higher in Group II, Group III, and Group IV than those of Group I. In addition, ISS score of Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

Group III was higher than that of Group II. Comparison of groups with respect to injury regions revealed no significant difference with regard to rate of abdominal trauma, while the rate of head trauma was markedly higher in Group IV than the other groups. Rate of thoracic trauma and multitrauma rate were significantly higher in Group III and Group IV than in Group I and Group II. The rate of extremity injury was higher in Group III and Group I than in Group II. When only patients presenting with LET were analyzed, it was noted that no patient was admitted to ICU. While no mortality was observed in Group I, Group III, or Group IV, 2 patients in Group II died in the emergency service due to severe head trauma. In addition, clinic admission rate and ISS score increased in proportion to BMI increase in groups other than Group IV. Comparison of groups by injury region was only performed between Group I, Group II, and Group III for injury regions other than extremities because 12 patients in Group IV only had extremity trauma. Although rate of head trauma was higher in Group I than in Group II and Group III, only the difference found in Group II was statistically significant. No significant difference existed between groups with respect to rate of thoracic trauma. Since no abdominal trauma existed in Group I or Group IV, a statistical comparison could not be done. Rate of extremity trauma was higher in 459


Durgun et al. The effect of body mass index on trauma severity and prognosis in trauma patients

Table 3. Analysis of body mass index groups in the whole patient population with respect to injury severity score and injury region Parameters Clinical admission, % (n)

Groups Group II 40.4 (207)

<0.001

Group III 41.2 (99)

<0.001

Group IV 50 (27)

<0.001

Group III 41.2 (99)

0.812

Group IV 50 (27)

0.192

Group III 41.2 (99)

Group IV 50 (27)

0.287

Group I 3.84±2.98

Group II 6.12±4.78

0.143

Group III 10.98±9.98

<0.001

Group IV 13.22±7.36

<0.001

Group III 10.98±9.98

<0.001

Group IV 13.22±7.36

0.006

Group III 10.98±9.98

Group IV 13.22±7.36

1.000

Group I 1 (6)

Group II 2.3 (12)

0.067

Group III 3.8 (9)

0.017

Group IV 11.1 (6)

0.001

Group III 3.8 (9)

0.341

Group IV 11.1 (6)

0.004

Group III 3.8 (9)

Group IV 11.1 (6)

0.038

Group I 9.46±11.93

Group II 14.93±14.46

0.001

Group III 59±14.73

0.001

Group IV 16.22±9.51

0.002

Group III 59±14.73

0.066

Group IV 16.22±9.51

1.000

Group III 59±14.73

Group IV 16.22±9.51

0.100

Group I 49.2 (291)

Group II 48.5 (249)

0.816

Group III 43.6 (105)

0.150

Group IV 72.2 (39)

0.001

Group III 43.6 (105)

0.220

Group I 25.9 (153)

Group II 40.4 (207)

Length of intensive care unit stay (days; Mean±SD)

Group II 6.12±4.78

Mortality, % (n)

Group II 2.3 (12)

Injury severity score (Mean±SD)

Group II 14.93±14.46

Head injury, % (n)

Group II 48.5 (249)

Thoracic injury, % (n)

Group IV 72.2 (39)

0.001

Group III 43.6 (105)

Group IV 72.2 (39)

<0.001

Group I 21.3 (126)

Group II 18.1 (93)

0.185

Group III 27.4 (66)

0.084

Group IV 38.9 (21)

0.003

Group III 27.4 (66)

0.003

Group IV 38.9 (21)

0.001

Group III 27.4 (66)

Group IV 38.9 (21)

0.098

Group I 7.6 (45)

Group II 6.4 (33)

0.445

Group III 10 (24)

0.229

Group IV 5.6 (3)

0.581

Group III 10 (24)

0.085

Group IV 5.6 (3)

1.000

Group III 10 (24)

Group IV 5.6 (3)

0.307

Group I 61.4 (363)

Group II 52.6 (270)

0.003

Group III 67.6 (163)

0.308

Group IV 66.7 (36)

0.447

Group III 67.6 (163)

0.001

Group IV 66.7 (36)

0.049

Group III 67.6 (163)

Group IV 66.7 (36)

0.906

Group I 33 (192)

Group II 34.5 (177)

0.479

Group III 47.5 (114)

0.001

Group IV 61.1 (33)

0.001

Group III 47.5 (114)

0.001

Group IV 61.1 (33)

0.001

Group IV 61.1 (33)

0.071

Group II 18.1 (93)

Abdominal injury, % (n)

Group II 6.4 (33)

Extremity injury, % (n)

Group II 52.6 (270)

Multitrauma, % (n)

Group II 34.5 (177) Group III 47.5 (114)

460

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Durgun et al. The effect of body mass index on trauma severity and prognosis in trauma patients

Table 4. Analysis of body mass index groups in terms of prognosis, injury severity score, and injury region among patients who were exposed to high-energy trauma Parameters Clinical admission, % (n)

Groups Group I 28.6 (108)

0.094 <0.001

Group III 36.4 (48)

0.186

Group IV 57.1 (24)

0.080

Group III 36.4 (48)

Group IV 57.1 (24)

0.017

Group I 3.84±2.98

Group II 6.12±4.78

0.143

Group III 10.98±9.98

<0.001

Group IV 13.22±7.36

<0.001

Group III 10.98±9.98

<0.001

Group IV 13.22±7.36

0.006

Group III 10.98±9.98

Group IV 13.22±7.36

1.000

Group I 1.6 (6)

Group II 2.5 (9)

0.389

Group II 6.12±4.78

Group II 2.5 (9)

Injury severity score (Mean±SD)

0.023

Group IV 14.3 (6)

<0.001 0.133 <0.001

Group III 25.52±14.66

<0.001

Group IV 19.29±8.47

0.025

Group III 25.52±14.66

<0.001

Group IV 19.29±8.47

1.000

Group III 25.52±14.66

Group IV 19.29±8.47

0.081

Group I 55.6 (210)

Group II 58.7 (213)

0.391

Group III 52.3 (69)

0.514

Group IV 92.9 (39)

<0.001

Group III 52.3 (69)

0.203

Group IV 92.9 (39)

<0.001

Group III 52.3 (69)

Group IV 92.9 (39)

<0.001

Group I 30.2 (114)

Group II 24.8 (90)

0.102

Group III 47.7 (63)

<0.001

Group IV 50 (21)

0.009

Group III 47.7 (63)

<0.001

Group IV 50 (21)

0.001

Group III 47.7 (63)

Group IV 50 (21)

0.797

Group I 11.9 (45)

Group II 8.3 (30)

0.101

Group III 8.3 (30)

0.603

Group IV 7.1 (3)

0.357

Group III 8.3 (30)

0.074

Group IV 7.1 (3)

0.801

Group III 8.3 (30)

Group IV 7.1 (3)

0.261

Group I 62.7 (237)

Group II 46.3 (168)

<0.001

Group III 61.4 (81)

0.785

Group IV 57.1 (24)

0.481

Group III 61.4 (81)

0.003

Group IV 57.1 (24)

0.182

Group III 61.4 (81)

Group IV 57.1 (24)

0.626

Group I 46.8 (177)

Group II 47.1 (171)

0.939

Group III 72.7 (96)

<0.001

Group IV 78.6 (33)

<0.001

Group III 72.7 (96)

<0.001

Group IV 78.6 (33)

<0.001

Group IV 78.6 (33)

0.451

Group II 46.3 (168)

Multitrauma, % (n)

Group III 6.8 (9)

Group II 18.97±15.21

Group II 8.3 (30)

Extremity injury, % (n)

<0.001

Group IV 14.3 (6)

Group II 24.8 (90)

Abdominal injury, % (n)

0.002

Group IV 14.3 (6)

Group I 12.63±13.60

Group II 58.7 (213)

Thoracic injury, % (n)

Group III 6.8 (9)

Group III 6.8 (9)

Group II 18.97±15.21

Head injury, % (n)

<0.001

Group IV 57.1 (24)

(days; Mean±SD)

Mortality, % (n)

Group II 43 (156) Group III 36.4 (48)

Group II 43.0 (156)

Length of intensive care unit stay

p

Group II 47.1 (171) Group III 72.7 (96)

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Durgun et al. The effect of body mass index on trauma severity and prognosis in trauma patients

Table 5. Analysis of body mass index groups with respect to prognosis, injury severity score, and injury region among patients who were exposed to low-energy trauma Parameters Clinical admission, % (n)

Groups Group II 34 (51)

0.006

Group III 47.2 (51)

<0.001

Group IV 25 (3)

0.750

Group III 47.2 (51)

0.032

Group IV 25 (3)

0.525

Group III 47.2 (51)

Group IV 25 (3)

0.142

Group I 0 (0)

Group II 2 (3)

0.038

Group III 0 (0)

Group I 21.1 (45)

Group II 34 (51)

Mortality, % (n)

Group II 2 (3)

Injury severity score (Mean±SD)

0.139

Group IV 0 (0)

0.621

Group II 5.16±4.61

0.081

Group III 7.89±7.02

<0.001

Group IV 5.50±2.71

1.000

Group III 7.89±7.02

<0.001

Group IV 5.50±2.71

1.000

Group III 7.89±7.02

Group IV 5.50±2.71

0.730

Group I 38 (81)

Group II 24 (36)

0.005

Group III 33.3 (36)

0.409

Group IV 0 (0)

0.008

Group III 33.3 (36)

0.099

Group IV 0 (0)

0.054

Group III 33.3 (36)

Group IV 0 (0)

0.017

Group I 5.6 (12)

Group II 2 (3)

0.087

Group III 2.8 (3)

0.252

Group IV 0 (0)

0.398

Group III 2.8 (3)

0.683

Group IV 0 (0)

0.621

Group III 2.8 (3)

Group IV 0 (0)

0.559

Group I 0 (0)

Group II 2 (3)

0.038

Group III 5.6 (6)

0.001

Group IV 0 (0) Group II 2 (3)

Extremity injury, % (n)

0.125

Group IV 0 (0)

0.621

Group IV 0 (0)

0.402

Group I 59 (126)

Group II 68 (102)

0.086

Group III 75 (81)

0.005

Group IV 100 (12)

0.005

Group III 75 (81)

0.222

Group IV 100 (12)

0.019

Group III 75 (81)

Group IV 100 (12)

0.049

Group I 7 (15)

Group II 4 (6)

0.222

Group III 16.7 (18)

0.007

Group IV 0 (0)

0.341

Group III 16.7 (18)

0.001

Group IV 0 (0)

0.480

Group IV 0 (0)

0.125

Group II 4 (6) Group III 16.7 (18)

Group III and Group IV than in Group I, and higher in Group IV than in Groups I, II, and III (Table 5). In the prediction of death, multiple logistic regression mod462

Group III 5.6 (6)

Group III 5.6 (6)

Group II 68 (102)

Multitrauma, % (n)

Group I 3.82±4.19

Group II 2 (n=3)

Abdominal injury, % (n)

Group III 0 (0) Group IV 0 (0)

Group II 24 (36)

Thoracic injur, % (n)

Group IV 0 (0)

Group III 0 (0)

Group II 5.16±4.61

Head injury, % (n)

p

els revealed that overweight, obese, and morbidly obese patients have increased odds of death. It was also seen that mortality rate increased in parallel with increasing BMI values (Table 6). Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Durgun et al. The effect of body mass index on trauma severity and prognosis in trauma patients

Table 6. Logistic regression analysis of body mass index groups with respect to exitus Groups

Exp (B)

95% CI for EXP (B)

Significant

Group I

9.377

4.514–19.480

<0.001

Group II

21.898

10.541–45.492

<0.001

Group III

35.620

17.146–73.999

<0.001

Group IV

114.280

55.009–237.413

<0.001

CI: Confidence interval.

DISCUSSION Trauma-induced injuries are among the most common reasons for emergency service admission. Multitrauma is usually seen in young people and male gender.[8] In a study on patients with blunt multitrauma, Altuncı et al. reported male:female ratio of 5:2.[9] According to 2012 statistics of Turkish Statistical Institute (TÜİK), 17.2% of the population aged 15 years or older was obese, 34.8% were overweight, 44.2% were normoweight, and 3.9% were underweight. According to these data, 52% of the Turkish population is above normal weight. The analysis of the available data in terms of gender revealed that 20.9% of Turkish women are obese and 30.4% are overweight, while 13.7% of men are obese and 39% are overweight. The predominance of female gender among obese persons is particularly striking.[10] In the present study, the male:female ratio was 3:2 in the whole study population. When analyzed by BMI, there was female gender predominance among obese persons and male predominance in the categories of overweight and normoweight, corresponding to TÜİK data. Among morbidly obese patients, number of men and women was equal, probably due to a limited sample size. When obese and morbidly obese patients were analyzed together, however, the ratio was in agreement with the literature data. This difference between overweight and obese patients may originate from higher rate of obesity among women due to the fact that majority of women living in our region are housewives, have a high fertility rate, have a tendency for obesity, and are less active than men in their daily lives. Studies investigating the cause and effect relationship between trauma and obesity have observed that obesity increased mortality and morbidity rates independently of injury severity when obese persons were exposed to severe blunt trauma.[11–13] Xiang et al. called attention to high injury risk in persons older than 18 years of age who had BMI ≥35.[14] Smith-Choban et al. showed that in patients who were exposed to blunt trauma, mortality rate was higher in patients having BMI >31 than in normoweight subjects, mortality rate increased in proportion to BMI increase, and that BMI was a poor prognostic factor in trauma.[15] In the 2012 TÜİK data, analysis of deaths occurring within 1 year (n=320967) demonstrated that rate of death from traffic accidents and falls Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

was 2.12% (6820), and male:female ratio was approximately 2:1.[16] In the present study, male:female ratio was 2:1, similar to that reported by TÜİK. In addition, similar to previous reports, mortality rate, clinic admission rate, ICU admission rate, and ISS increased in parallel with BMI increase, with mortality rate in first place. This increase, especially in morbid obesity, is the most striking aspect of the present study. In the opinion of the authors, this occurred because obese persons are exposed to greater force due to their greater weight, and thus sustain more severe injuries than normoweight persons in crash injuries. Furthermore, high incidence of comorbid conditions accompanying obesity such as DM, insulin resistance, chronic obstructive pulmonary disease, hypertension, hyperlipidemia, coronary artery disease, and other vascular diseases, as well as lower physiological reserve in obese persons may contribute to deterioration of general condition of these patients.[17] Studies investigating the poor prognostic impact of obesity in trauma cases showed that head trauma was less common and extremity trauma was more common in obese persons than normoweight persons.[6,17,18] It has been demonstrated that rate of extremity injury was higher and rate of abdominal injury was lower.[6] Boulanger et al. demonstrated that rates of thoracic, lower extremity, and pelvic injuries were higher, and rate of head trauma was lower in obese persons who were exposed to HET. The authors explained higher rate of lower extremity fractures in HET with increased burden on lower extremities of greater body mass.[18] Arbabi et al. found high rate of lower extremity fracture in motor vehicle accidents,[19] and Gabriel et al. showed an increased rate of extremity trauma in overweight persons suffering motor vehicle accidents.[17] The present study had results similar in many aspects to those of previous studies. Finding of higher rate of injuries involving all regions except head in obese and morbid obese patients was compatible with previous literature findings. However, similar rates of head trauma in patient groups except morbidly obese group, which had a significantly higher rate, contradicts previous reports. We think that this difference in the present study originated as a result of smaller number of morbidly obese patients than other patients. The finding of higher rates of extremity trauma, thoracic trauma, and especially multitrauma in obese and morbidly obese patients compared to normoweight and overweight patients supports the findings of earlier studies. Another noteworthy point in the present study was that clinic admission rate, length of ICU stay, and ISS score were significantly greater in obese and morbidly obese patients than normoweight and overweight patients, and they increased in proportion to BMI increase when patients who experienced HET were analyzed separately. Clinic admission rate, mortality rate, and length of ICU stay were significantly higher in morbidly obese group than in other groups. Although the finding of higher rate of head trauma in morbidly obese patients compared to other groups contradicted literature data, higher 463


Durgun et al. The effect of body mass index on trauma severity and prognosis in trauma patients

rates of thoracic trauma and multitrauma were in agreement with the literature. We think that this disagreement in head trauma data was due to fact that traffic accidents are more common among HET patients, and there is a lack of awareness and appreciation about the need to take safety measures such as fastening seat belt that originates in the socioeconomic level of our region. The results indicated that increased BMI was a poor prognostic factor in cases of HET. It was observed that rate of extremity trauma increased in proportion to BMI increase. All morbidly obese patients who presented with LET such as simple falls only had extremity trauma. This can be explained by excessive burden of increased body mass upon extremities as BMI increases. and the difficulty that these patients experience in balanced walking.

Conclusion Obesity increases mortality and morbidity independently of injury severity in trauma patients. As BMI increased, length of hospital stay, rate and length of ICU stay, rate of extremity injury, multitrauma, and death also increased. Serious extremity traumas can be seen even in instances of LET in obese patients, and this is particularly true for the morbidly obese. Conflict of interest: None declared.

REFERENCES 1. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999;341:1097–105. 2. National Institutes of Health. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: the Evidence Report. Washington, DC: National Institutes of Health Publication; 1998. p. 98–4083. 3. WISQARS Leading Causes of Death Reports, 1999–2003. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2006. Available at: http://webappa.cdc.gov/sasweb/ncipc/leadcaus10.html. Accessed on: August 8, 2006. 4. Ciesla DJ, Moore EE, Johnson JL, Burch JM, Cothren CC, Sauaia A. Obesity increases risk of organ failure after severe trauma. J Am Coll Surg 2006;203:539–45. 5. Ryb GE, Dischinger PC. Injury severity and outcome of overweight and

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obese patients after vehicular trauma: a crash injury research and engineering network (CIREN) study. J Trauma 2008;64:406–11. 6. Brown CV, Neville AL, Salim A, Rhee P, Cologne K, Demetriades D. The impact of obesity on severely injured children and adolescents. J Pediatr Surg 2006;41:88–91. 7. Lee WT, Murphy D, Kagda FH, Thambiah J. Proximal femoral locking compression plate for proximal femoral fractures. J Orthop Surg (Hong Kong) 2014;22:287–93. 8. Dur A, Cander B, Kocak S, Girisgin S, Gul M, Koyuncu F. Multitrauma patients and trauma scoring systems in emergency-intensive care unit. J Acad Emerg Med 2009;8:24–7. 9. Altuncı Y, Aldemir M, Guloglu C, Ustundag M, Guloglu C. The effective factors in emergency department observation on hospitalization requirement and mortality in blunt trauma patients. J Acad Emerg Med 2010;9:117–20. 10. Turkish Statistical Institute. Turkey Health Survey, 2012, April 2013. Available at: http://www.turkstat.gov.tr/PreHaberBultenleri. do?id=13490. Accessed on: December 25, 2014. 11. Neville AL, Brown CV, Weng J, Demetriades D, Velmahos GC. Obesity is an independent risk factor of mortality in severely injured blunt trauma patients. Arch Surg 2004;139(9):983–7. 12. Maheshwari R, Mack CD, Kaufman RP, Francis DO, Bulger EM, Nork SE, et al. Severity of injury and outcomes among obese trauma patients with fractures of the femur and tibia: a crash injury research and engineering network study. J Orthop Trauma 2009;23:634–9. 13. Hoffmann M, Lefering R, Gruber-Rathmann M, Rueger JM, Lehmann W. Trauma Registry of the German Society for Trauma Surgery. The Impact of BMI on Polytrauma Outcome. Injury 2012;43:184–8. 14. Xiang H, Smith GA, Wilkins JR 3rd, Chen G, Hostetler SG, Stallones L. Obesity and risk of nonfatal unintentional injuries. Am J Prev Med 2005;29:41–5. 15. Choban PS, Weireter LJ Jr, Maynes C. Obesity and increased mortality in blunt trauma. J Trauma 1991;31:1253–7. 16. Turkish Statistical Institute. Causes of Death Statistics, 2010, 2011 and 2012, April 2013. Available at: http://www.turkstat.gov.tr/PreHaberBultenleri.do?id=15847. Accessed on: December 25, 2014. 17. Ryb GE, Dischinger PC. Injury severity and outcome of overweight and obese patients after vehicular trauma: a crash injury research and engineering network (CIREN) study. J Trauma 2008;64:406–11. 18. Boulanger BR, Milzman D, Mitchell K, Rodriguez A. Body habitus as a predictor of injury pattern after blunt trauma. J Trauma 1992;33:228– 32. 19. Arbabi S, Wahl WL, Hemmila MR, Kohoyda-Inglis C, Taheri PA, Wang SC. The cushion effect. J Trauma 2003;54:1090–3.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Travma hastalarında vücut kitle indeksinin travma şiddeti ve prognoza etkisi Dr. Hasan Mansur Durgun,1 Dr. Recep Dursun,1 Dr. Yılmaz Zengin,1 Dr. Ayhan Özhasenekler,2 Dr. Murat Orak,1 Dr. Mehmet Üstündağ,1 Dr. Cahfer Güloğlu1 1 2

Dicle Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Diyarbakır Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Ankara

AMAÇ: Son yıllarda tüm dünyada olduğu gibi Türkiye’de de obezite çok ciddi bir toplum sorunu olacak şekilde giderek artmaktadır. Bugüne kadar obezitenin dahili hastalıklarıyla ilgili birçok çalışma yapılmasına rağmen travma hastalarında obezitenin prognoz üzerindeki etkisini inceleyen çok az çalışma mevcuttur. Bu çalışmada travma hastalarında vücut kitle indeksinin (VKİ) travma şiddeti ve prognoz üzerine etkilerini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Bu ileriye yönelik çalışmada 01 Haziran 2013 ile 31 Mayıs 2014 tarihleri arasında Dicle Üniversitesi Tıp Fakültesi Hastanesi Acil Servisi Travma Ünitesi’ne başvuran 15 yaş üstü travma hastaları incelendi. Hastalar maruz kaldıkları travmanın şiddetine göre yüksek enerjili travma (YET) ve düşük enerjili travma (DET) olmak üzere iki gruba ayrıldı. Hastalar BMI (kg/m2) değerlerine göre 4 gruba ayrıldı: Grup I; BMI<25 (normal kilolu grup), Grup II; VKİ 25–29.9 (kilo fazlalığı grubu), Grup III; VKİ 30–34.9 (obez grup), Grup IV; VKİ ≥35 (morbid obez grup). BULGULAR: Tüm hastaların gruplar arası farkları incelendiğinde gruplar arasında baş yaralanması, toraks yaralanması, ekstremite yaralanması, çoklu travma oranı, klinik yatış oranı ve mortalite açısından belirgin fark saptandı (p<0.001). Karın yaralanması açısından gruplar arasında belirgin bir fark görülmedi (p=0.347). TARTIŞMA: Travma hastalarında VKİ arttıkça klinik yatış oranı, yoğun bakımda yatış süresi, mortalite oranı, multitravma oranı ve ISS skoru artmaktadır. Anahtar sözcükler: Travma, travma şiddet skoru; vücut kitle indeksi. Ulus Travma Acil Cerrahi Derg 2016;22(5):457–465

doi: 10.5505/tjtes.2016.93385

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ORIGIN A L A R T IC L E

Evaluation of the open and laparoscopic appendectomy operations with respect to their effect on serum IL-6 levels Mehmet Kadir Bartın, M.D.,1 Özgür Kemik, M.D.,2 Mehmet Ali Çaparlar, M.D.,3 Mustafa Taner Bostancı, M.D.,3 Muzaffer Önder Öner, M.D.1 1

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

2

Department of General Surgery, Yüzüncü Yıl University Faculty of Medicine, Van-Turkey

3

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

ABSTRACT BACKGROUND: Postoperative serum inflammatory cytokine levels are thought to reflect the magnitude of surgical stress. Cytokine interleukin-6 (IL-6) is an early marker of systemic inflammatory response and tissue damage. This study evaluated levels of IL-6 after open and laparoscopic appendectomy to compare the degree of surgical stress associated with these procedures. METHODS: IL-6 levels were measured pre- and postoperatively in the plasma of 200 consecutive patients with a diagnosis of acute appendicitis. After preoperative randomization, 100 patients underwent open appendectomy, and 100 patients underwent laparoscopic appendectomy. RESULTS: Preoperative concentrations of IL-6 were 65.22±4.76 pg/mL in the open appendectomy group and 65.73±6.34 pg/mL in the laparoscopic appendectomy group (p=0.752). Postoperative levels were 105.28±16.14 pg/mL and 76.11±16.18 pg/mL, respectively (p<0.05). CONCLUSION: Lower postoperative serum IL-6 levels suggest that laparoscopic surgery is associated with lower degree of surgical stress. Laparoscopic appendectomy has significant advantage over open appendectomy due to more rapid postoperative recovery. Keywords: Interleukin (IL)-6; laparoscopic appendectomy; open appendectomy.

INTRODUCTION Although its characteristics and treatment have been accurately defined, acute appendicitis is an urgent surgical condition that can have high mortality and morbidity rates secondary to perforation as result of delayed decision to operate. Therefore, the general tendency is in favor of operating before clinical findings are completely sustained. Consequently, negative appendectomy rates are as high as 30%, which is considered acceptable worldwide.[1] Negative appendectomy has a negligible mortality rate and only 10% morbidity. Majority of morbidities are traumas due to perioperative Address for correspondence: Mustafa Taner Bostancı, M.D. Dışkapı Yıldırım Beyazıd Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara, Turkey Tel: +90 312 - 596 20 00 E-mail: mtanerbostanci@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):466–470 doi: 10.5505/tjtes.2016.47650 Copyright 2016 TJTES

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surgery and risk of bride ileus or incisional hernia, which are not life-threatening.[1] There is much lower incidence of perioperative trauma causing critical complications during aggressive surgical treatment of acute appendicitis with laparoscopic appendectomy compared to open conventional surgery. The aim of the present study was to evaluate cases of laparoscopic and open technique appendectomy due to diagnosis of acute appendicitis using interleukin-6 (IL-6) response, a measure of surgical stress, to compare methods of surgical intervention.

MATERIALS AND METHODS This study was approved by the ethics committee of Yüzüncü Yıl University Faculty of Medicine Research Hospital on December 1, 2010 and given approval number 003. A total of 200 male and female patients of American Society of Anesthesiologists (ASA) physical status classification 1 or 2, between 16 and 70 years of age, who consecutively presented at the emergency surgery department between July 2010 and December 2014 with prediagnosis of acute appendicitis were included in the study. Patients were evenly distributed into 2 groups: Group 1 consisted of 100 Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Bartın et al. Evaluation of the open and laparoscopic appendectomy operations with respect to their effect on serum IL-6 levels

patients who had laparoscopic appendectomy, and Group 2 consisted of 100 patients who underwent conventional open appendectomy. Patients with cardiovascular or pulmonary system disorders, history of abdominal surgery, known allergic history to agents used, history of preoperative anti-inflammatory drug use, infection within abdominal wall, portal hypertension or hepatic cirrhosis, antibiotic medication use, or immunodeficiency were excluded from the study. Unconscious or non-cooperative patients, pregnant patients, and morbidly obese patients were also excluded. All patients observed preoperative 8-hour period of oral fasting. Premedication, induction of anesthesia, endotracheal intubation, and maintenance of anesthesia were performed according to hospital protocols. Cefazolin sodium 1 gr was administered intravenously as prophylactic antibiotic after induction of anesthesia. Five cc venous blood samples were obtained from upper extremity veins just before and 24 hours after the operation for serum IL-6 level testing. Blood samples were taken in dry test tubes and then immediately centrifuged at 3000 rpm for 10 minutes. Top layer of serum was aspirated and put into snap-cap Eppendorf tubes (Eppendorf, Hamburg, Germany) and stored at -70°C in Aeroset refrigerator (Abbott Laboratories, Chicago, IL, USA) in order to perform measurements using spectrophotometry as well as routine tests. McBurney incision was used to enter abdomen of 84 of the patients who underwent open appendectomy and subumbil-

ical median incision was used on 4 patients and paramedian incision was used on 12 patients. All laparoscopic appendectomies were completed using intra-abdominal method with a total of 3 ports. Intra-abdominal area was explored using a 10 mm port inserted through the umbilicus. Second 10 mm port was inserted into the abdomen with a direct view at a point approximately 10 cm below the umbilicus and through the linea alba. The final port, 5 mm in size, was inserted into the abdomen through the intersection point of midclavicular line and subcostal arch with a direct view. A silastic drain was used on 11 patients who underwent open appendectomy and 5 patients who underwent laparoscopic appendectomy. Intraoperative macroscopic findings of the patients were recorded. After the operation, pathological results of appendix material and duration of hospital stay were recorded. Serum samples were tested using enzyme-linked immunosorbent assay method. Specificity and sensitivity of the kit were 90% and 95%, respectively.[2] Comparison of group means with respect to continuous variables was performed using one-way analysis of variance. Duncan’s multiple range test was used to compare the 2 groups. Pearson correlation coefficient was used to determine the association between continuous variables and chi-square test was used for categorical variables. Level of statistical significance was 5% (p<0.05) and SPSS statistical package software (version 16.0; SPSS Inc., Chicago, IL, USA) was used for data analysis, including Mann-Whitney U test and Friedman test.

Table 1. Distribution of demographic data Age (Mean±SD) Gender (Female/Male)

Group 1 (n=100)

Group 2 (n=100)

p

30.04±9.26

33.04±11.28

0.309

64/36

48/52

0.254

SD: Standard deviation.

Table 2. Distribution of histopathological diagnoses Histopathological diagnosis

Group 1

Group 2

p

Total

n % n % n %

Normal

4 2 4 2 >0.05 8 4

Non-suppurative

64 32 40 20 >0.05 104 52

Suppurative

16 8 28 14 >0.05 44 22

Subacute

12 6 20 10 >0.05 32 16

Lymph node hyperplasia 4 2 8 4 >0.05 12 6 Total (n)

100 50 100 50

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200 100

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Bartın et al. Evaluation of the open and laparoscopic appendectomy operations with respect to their effect on serum IL-6 levels

Table 3. Preoperative and postoperative IL-6 level

Group 1 (n=100)

Group 2 (n=100)

p

Preoperative IL-6 (pg/mL), Mean±SD

65.73±6.34

65.22±4.76

0.752

Postoperative IL-6 (pg/mL), Mean±SD

76.11±16.18

105.28±16.14

<0.001*

p

>0.05 <0.001*

SD: Standard deviation.

Table 4. Length of hospital stay

Group 1 (n=100)

Group 2 (n=100)

p

33.36±4.38

37.68±4.68

0.006*

Duration of hospital stay (h), Mean±SD SD: Standard deviation.

RESULTS Distribution of the Demographic Data No statistically significant difference between groups was found in the demographic data (p>0.05); the distribution is presented in Table 1.

Distribution of the Histopathological Diagnoses

No statistically significant difference with respect to histopathological diagnoses was found between the groups (p>0.05); the distribution is presented in Table 2.

Preoperative and Postoperative IL-6 Level No significant difference was found between Group 1 and Group 2 patients with respect to IL-6 levels in the preoperative blood samples (p<0.05). A statistically significant difference was found when comparing preoperative and postoperative serums IL-6 levels in Group 2 patients (p<0.001). When postoperative serum levels were analyzed; IL-6 levels were higher in Group 2 than in Group 1 (p<0.001). A positive correlation was observed between Group 2 and Group 1 (r=0.45; p<0.001). Preoperative and postoperative IL-6 levels are presented in Table 3.

Duration of Hospital Stay The duration of hospital stay was statistically lower in Group 1 compared to Group 2 (p<0.05) Hospital stay data are presented in Table 4.

DISCUSSION IL-6 plays an important role in regulation of inflammatory cells in the immune system; it participates in either proinflammatory or anti-inflammatory reactions. Free tissue injury and 468

infections are the major factors that trigger synthesis of IL-6. It affects the immune system via pattern known as hepatic acute-phase reactions. In this process, cytokines increase the release of acute phase proteins by behaving as general antibodies. Though IL-6 increases to a certain degree in response to infection, serum IL-6 level generally increases in reaction to damage of free tissue. Therefore, IL-6 levels don’t increase greatly in the picture of acute appendicitis as result of infection in the gastrointestinal system but do increase in cases where tissue damage occurs due to surgical intervention.[3–5] In a study that supports this conclusion, Yildirim et al.[1] investigated leukocyte count, IL-6, and C-reactive protein (CRP) levels in patients with prediagnosis of acute appendicitis. They stated that leukocyte count and CRP levels may be helpful in diagnosis of acute appendicitis. However, they did not evaluate increase in serum IL-6 level as particularly statistically significant with respect to diagnosis of acute appendicitis. Bachmann et al.[6] determined in literature reviews that inflammatory predictors such as IL-1, IL-2 and IL-10 may provide diagnostic contribution with a low error rate for inexperienced physicians and surgeons. It has been stated that serum levels of these predictors increase significantly in complicated appendicitis, whereas less of an increase occurs in serum levels of IL-6 and IL-8.[7] Instead, IL-6 and IL-8 levels see greater increase secondary to perioperative trauma. [6,8] Serum levels of IL-6 were analyzed in the present study because of this response of these cytokines to stress such as surgical trauma. Yahara et al.[9] observed in their study that CRP and granulocyte/monocyte colony-stimulating factor levels were high in tissue samples obtained from peritoneal cavity of patients operated on laparoscopically and with open surgery due to diagnosis of acute appendicitis. Preoperative and postoperative CRP and granulocyte/monocyte-colony stimulating facUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Bartın et al. Evaluation of the open and laparoscopic appendectomy operations with respect to their effect on serum IL-6 levels

tor levels of these patients were also high. High preoperative IL-6 levels were detected but were not statistically significant. However, postoperative elevation of this interleukin in conventional surgery patients was significantly higher than in those who had laparoscopic surgery. As expected, total leukocyte and neutrophil counts were high in preoperative period and also in postoperative period after exposure to stress of surgical trauma. In particular, increased neutrophil count may be accepted as a useful marker to indicate level of inflammation in diagnosis of acute appendicitis.[10–12] As in the literature, the present study also found that the difference in serum IL-6 levels tested preoperatively between Group 1 patients (65.7±6.3 pg/mL), who had laparoscopic appendectomy, and Group 2 patients (65.2±4.7 pg/mL), who underwent conventional appendectomy, was low and statistically insignificant (p=0.752). The serum IL-6 levels tested at postoperative 24th hour in both groups (76.1±16.1 pg/mL in Group 1 and 105.2±16.1 pg/mL in Group 2) were remarkably high, especially in the conventional surgery patients, and the finding was statistically extremely significant (p<0.001). Less surgical trauma in appendectomy leads to early recovery and return to full activity, as was supported by a large-scale meta-analysis conducted by the Cochrane Colorectal Cancer Group.[13] Minimal trauma to abdominal wall during trocar placement and minimal manipulation of intestine causes less pain and encourages faster recovery.[14] The secondary finding of the present study was that mean duration of hospital stay of laparoscopic appendectomy patients was found to be statistically significantly shorter. This advantage of laparoscopic appendectomy was also noted in recent meta-analysis conducted by Sauerland et al.[15] Over time, surgical methods have evolved from open surgery to less invasive techniques. Laparoscopic surgery has also been subject of evolution. Recently, Concha et al.[16] published a review study in which single-incision laparoscopic appendectomy was acknowledged as applicable and comparable procedure in selected patients.

Conclusion Surgical interventions create trauma in the body and thereby induce systemic stress response. We have concluded that surgical stress induced by laparoscopic appendectomy is less severe than conventional method of surgical treatment of acute appendicitis. Additionally, the authors observed that hospital stay was shorter for patients who underwent laparoscopic appendectomy compared to open surgery.

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Conflict of interest: None declared.

REFERENCES 1. Yildirim O, Solak C, Koçer B, Unal B, Karabeyoğlu M, Bozkurt B, et al. The role of serum inflammatory markers in acute appendicitis and their success in preventing negative laparotomy. J Invest Surg 2006;19:345–52. 2. Kemik O, Kemik AS, Dülger AC, Hasırcı İ, Daştan E, Bartın MK, et al. Karaciğer metastazlı kolon kanserli hastalarda interlökin-6 düzeyleri. Van Tıp Dergisi 2010;17:42–5. 3. Braga M, Vignali A, Gianotti L, Zuliani W, Radaelli G, Gruarin P, et al. Laparoscopic versus open colorectal surgery: a randomized trial on shortterm outcome. Ann Surg 2002;236:759–67. 4. Gupta A, Watson DI. Effect of laparoscopy on immune function. Br J Surg 2001;88:1296–306. 5. Groselj-Grenc M, Repse S, Vidmar D, Derganc M. Clinical and laboratory methods in diagnosis of acute appendicitis in children. Croat Med J 2007;48:353–61. 6. Bachmann LM, Bischof DB, Bischofberger SA, Bonani MG, Osann FM, Steurer J. Systematic quantitative overviews of the literature to determine the value of diagnostic tests for predicting acute appendicitis: study protocol. BMC Surg 2002;2:2. 7. Türkyilmaz Z, Sönmez K, Karabulut R, Elbeğ S, Moralioğlu S, Demirtola A, et al. Sequential cytokine levels in the diagnosis of appendicitis. Scand J Clin Lab Invest 2006;66:723–31. 8. Montalto AS, Impellizzeri P, Grasso M, Antonuccio P, Crisafi C, Scalfari G, et al. Surgical stress after open and transumbilical laparoscopic-assisted appendectomy in children. Eur J Pediatr Surg 2014;24:174–8. 9. Yahara N, Abe T, Morita K, Tangoku A, Oka M. Comparison of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor production by the peritoneum in laparoscopic and open surgery. Surg Endosc 2002;16:1615–9. 10. Eriksson S, Granström L, Olander B, Wretlind B. Sensitivity of interleukin-6 and C-reactive protein concentrations in the diagnosis of acute appendicitis. Eur J Surg 1995;161:41–5. 11. Hallan S, Asberg A, Edna TH. Additional value of biochemical tests in suspected acute appendicitis. Eur J Surg 1997;163:533–8. 12. Sack U, Biereder B, Elouahidi T, Bauer K, Keller T, Tröbs RB. Diagnostic value of blood inflammatory markers for detection of acute appendicitis in children. BMC Surg 2006;6:15. 13. Wei B, Qi CL, Chen TF, Zheng ZH, Huang JL, Hu BG, et al. Laparoscopic versus open appendectomy for acute appendicitis: a metaanalysis. Surg Endosc 2011;25:1199–208. 14. Cipe G, Idiz O, Hasbahceci M, Bozkurt S, Kadioglu H, Coskun H, et al. Laparoscopic versus open appendectomy: where are we now? Chirurgia (Bucur) 2014;109:518–22. 15. Sauerland S, Jaschinski T, Neugebauer EA. Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev 2010;10:CD001546. 16. Concha JA, Cartes-Velásquez R, Delgado CM. Single-incision laparoscopic appendectomy versus conventional laparoscopy in adults. A systematic review. Acta Cir Bras 2014;29:826–31.

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Bartın et al. Evaluation of the open and laparoscopic appendectomy operations with respect to their effect on serum IL-6 levels

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Açık ve laparoskopik apendektomi ameliyatlarının serum IL-6 düzeylerine etkisi açısından değerlendirilmesi Dr. Mehmet Kadir Bartın,1 Dr. Özgür Kemik,2 Dr. Mehmet Ali Çaparlar,3 Dr. Mustafa Taner Bostancı,3 Dr. Muzaffer Önder Öner1 1 2 3

Van Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Van Yüzüncü Yıl Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Van Dışkapı Yıldırım Beyazıd Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Ameliyat sonrası enflamatuvar sitokinlerin serum düzeylerinin cerrahi stresin boyutunu yansıttığı düşünülür. Sitokin IL-6, sistemik enflamatuvar yanıtın ve doku hasarının erken bir belirtecidir. Bu çalışmanın amacı, açık ve laparoskopik apendektomi sonrası serum IL-6 düzeylerini değerlendirerek bu prosedürlere bağlı gelişen cerrahi stres düzeyini karşılaştırmaktır. GEREÇ VE YÖNTEM: Akut apendisit tanısı almış ardarda gelen 200 hastanın plazmasında ameliyat öncesi ve sonrası IL-6 düzeyleri ölçüldü. Ameliyat öncesi gelişigüzel seçim ile 100 hastaya açık apendektomi ve 100 hastaya da laparoskopik apendektomi yapıldı. BULGULAR: Ameliyat öncesi IL-6 konsantrasyonu açık grupta 65.22±4.76 pg/ml iken laparoskopik grupta ise 65.73±6.34 pg/ml idi (p=0.752). Ameliyat sonrası düzeyler ise sırasıyla 105.28±16.14 pg/ml ve 76.11±16.18 pg/ml idi (p<0.05). TARTIŞMA: Serum IL-6 düzeylerinin daha düşük olması laparoskopik cerrahide cerrahi stres düzeyinin daha düşük olması ile ilişkilidir. Laparoskopik apendektominin daha hızlı ameliyat sonrası iyileşme nedeniyle açık apenedektomiye göre belirgin avantajı mevcuttur. Anahtar sözcükler: Açık apendektomi; Interlökin(IL)-6; laparoskopik apendektomi. Ulus Travma Acil Cerrahi Derg 2016;22(5):466–470

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doi: 10.5505/tjtes.2016.47650

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ORIGIN A L A R T IC L E

Pre-operative stool analysis for intestinal parasites and fecal occult blood in patients with acute appendicitis Sinan Hatipoğlu, M.D.,1 Uğur Lök, M.D.,2 Umut Gülaçtı, M.D.,2 Tuncay Çelik, M.D.3 1

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

2

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

3

Department of Parasitology, Adıyaman University Faculty of Medicine, Adıyaman-Turkey

ABSTRACT BACKGROUND: Etiology of acute appendicitis (AA) rarely involves parasitic infections of gastrointestinal (GI) tract. Preoperative diagnosis of parasitic infections in appendix remains difficult, although parasites can sometimes be observed inside the lumen during histopathological examination. The aim of the present study was to prospectively screen prevalence and species of intestinal parasites and adherence of fecal occult blood (FOB) in patients admitted to emergency department (ED) with clinical symptoms of AA who underwent appendectomy. METHODS: Demographic and stool analysis data of a total of 136 patients (≥13 years old) who underwent appendectomy between July 2009 and December 2014 were prospectively assessed, and histopathological data of all patients were retrospectively assessed. RESULTS: In histopathological examination after appendectomy, of 136 patients, 75.5% (n=103) had AA, 11.1% (n=15) had perforated appendicitis (PA), and 13.2% (n=18) had a negative appendicitis (normal appendix, NA). Pre-operative stool analysis revealed that 25% (n=34) had intestinal parasites and 14.7% (n=20) of patients had positive fecal occult blood test (FOBT). Those with positive FOBT represented 9.7% (n=10) of 103 AA patients, 53.3% (n=8) of 15 PA patients, and 11.1% (n=2) of 18 NA patients; this was statistically more significant for PA than other groups (p<0.001). CONCLUSION: Presence of intestinal parasites in stool might not be associated with appendicitis, but it can occasionally lead to pathological findings of appendicitis. A positive FOBT may be a predictor for PA. Keywords: Appendicitis; fecal occult blood; intestinal parasites; stool analysis

INTRODUCTION Acute appendicitis (AA) is an important cause of acute abdominal pain, and incidence of appendicitis in all age groups is 7%. In addition, appendicitis is one of the most common surgical consultations in outpatient or emergency department (ED).[1] Appendicitis is an emergency situation with highest unknown rate of etiological factors, even though clear diagnosis and treatment strategies have been established for more than 100 years. Etiology of appendicitis rarely involves Address for correspondence: Uğur Lök, M.D. Adıyaman Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Adıyaman, Turkey Tel: +90 416 - 223 16 90 E-mail: ugurlok@hotmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):471–476 doi: 10.5505/tjtes.2016.83883 Copyright 2016 TJTES

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parasitic infections of gastrointestinal (GI) tract in developed countries.[2] Preoperative diagnosis of parasitic infections in appendix remains difficult, although parasites can sometimes be observed inside the lumen during histopathological examination. Intestinal parasites cause significant morbidity and mortality worldwide.[3] Parasites within resected appendix specimens are usually an incidental finding, but the relationship between parasites and appendicitis is unclear and remains controversial. Nevertheless, many parasites have been found in the lumen of normal appendix (NA).[4–7] Intestinal parasites are rarely observed in relation to acute inflammation of appendix but can definitely be responsible for luminal obstruction leading to appendicitis. Ova release from female parasites may be a cause of appendiceal luminal obstruction, which consequently is followed by bacterial overgrowth, finally resulting in AA.[8] Intestinal parasites, e.g., Enterobius vermicularis (most frequently), Ascaris lumbricoides, Schistosoma subspecies, Taenia subspecies, Trichuris trichuria, and Entamoeba histolytica, are among rare causes of appendicitis.[2,9–16] 471


Hatipoğlu et al. Pre-operative stool analysis for intestinal parasites and fecal occult blood in patients with acute appendicitis

However, to the best of our knowledge, while there are many studies investigating the etiology and diagnostic methods of AA, there are few prospective studies examining FOB and direct stool analysis for intestinal parasites in patients with pre-diagnosed AA. Most other studies have been performed postoperatively and retrospectively in appendectomy specimen. It is known that definitive diagnosis of AA is made histopathologically. If parasitic infection is proven to be an origin of appendicitis, it may be crucial from both cost effectiveness and public healthcare perspectives. Therefore, the aim of the present study was to investigate prospectively prevalence and species of intestinal parasites via stool analysis in patients with AA who were admitted to tertiary care in a rural city hospital ED and who underwent appendectomy.

MATERIALS AND METHODS Study Setting This study was conducted prospectively between July 2009 and December 2014 in the departments of academic emergency medicine and general surgery of a rural city tertiary care hospital at Adıyaman University Faculty of Medicine. The study was approved by the university ethics committee. Verbal informed consent was obtained from each patient before study enrollment. Informed consent consisted of patient name, aim, and expected benefits of the study, and rights of patients during the study.

Study Population A total of 136 patients over 13 years of age presenting consecutively to ED during the study period with appendicitis, diagnosed by clinical and laboratory methods, were included in scope of study. Patients presenting with parasitic or nonparasitic bowel disease in past medical history, those who did not want to participate in study, or who referred to ED outside of working hours, were excluded. Eligibility of patients for study was determined by an attending emergency physician and 1 general surgeon between 8:00 a.m. and 4:00 p.m. Stool analysis, medical, and pathology records of all patients were evaluated in detail. Diagnosis of appendicitis or NA was made with perioperative macroscopic evaluation. Pathology department records about histopathological assessment of appendicitis specimens were reviewed for all patients retrospectively.

Study Protocol Study data were prospectively collected by emergency physicians and the general surgeon. Demographic features of patients, physical examination findings, laboratory test results at ED presentation, complications that occurred during hospital admission, and final diagnosis and outcome of study patients were recorded on the study form. Diagnosis of AA was performed by the same attending emergency physicians and senior general surgeon. From each patient who was diagnosed 472

with AA and ultimately underwent appendectomy, a stool sample was collected to analyze for parasites and FOB before surgery. All stool samples were rapidly analyzed (in 1 hour) in parasitology department of hospital between 8:00 a.m. and 4:00 p.m. Patients with intestinal parasites identified in stool analysis were directed to outpatient clinic for infectious diseases for medical treatment and follow-up after discharge. Surgery was performed by same general surgeon who first examined participants. Preoperatively, patients received a prophylactic dose of second generation cephalosporin (1000 mg intravenously) and underwent open approach appendectomy via McBurney incision under general anesthesia. Laparoscopic approach was not performed for appendectomy due to technical inadequacy of institute. Abdominal exploration was performed in all patients with NA to exclude possible Meckel’s diverticulum. A negative appendectomy was defined as one performed due to clinical pre-diagnosis of AA but in which appendix tissue is found to be normal on routine histopathological examination.

Laboratory Measurements A 9 mL sample of venous blood from antecubital area was obtained from each patient and stored in tubes for routine initial laboratory analysis. Stool sample from each patient was sent to parasitological laboratory inside a closed envelope and disposable, leak-proof, sealed container. Each stool sample was prepared with native-lugol and assessed by direct microscopy. Hemoglobin was screened in the feces using a guaiac-based technique. Entamoeba histolytica-specific antigen was investigated in diarrhea specimens using enzyme-linked immunosorbent assay (ELISA). Accepted stool specimens were studied by the laboratory without delay.

Data Analysis All values were expressed as mean±SD and percentage. To evaluate differences among groups, Pearson chi-square test was used. To analyze categorical data and frequency distribution, nonparametric chi square test was used. P values <0.05 were considered statistically significant. Data were analyzed using SPSS software (version 17.0; SPSS Inc., Chicago, IL, USA).

RESULTS A total of 136 patients pre-diagnosed with AA were admitted to ED during the study period. Of these patients, 61% (n=83) were male and 39% (n=53) were female. Mean age was 24.1±4.3 years (range: 13-68 years). Histopathological examination results were 75.7% (n=103) AA, 11.1% (n=15) PA, and 13.2% (n=18) NA (Table 1, Fig. 1). Stool analysis showed that 34 (25%) cases had intestinal parasites. Of these 34 patients, incidence of intestinal parasites in Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


HatipoÄ&#x;lu et al. Pre-operative stool analysis for intestinal parasites and fecal occult blood in patients with acute appendicitis

120

Mean age, years (min-max)

24.1Âą4.3 (13â&#x20AC;&#x201C;68)

60

Acute appendicitis (n)

103

40

Perforated appendicitis (n)

15

20

Normal appendix (n)

18

0

Intestinal parasites (n)

34

34 15

Acute appendicitis

10

Perforated appendicitis

8

Normal appendix

2

Patients with diarrhea (n)

12

ap

25

20

18 13.2

11

pe

Positive fecal occult blood (n)

75.7

14.7

12

8.8

fe P ca o l o sit cc ive ul t Pa tie nt di s ar w rh ith ea

80

I pa nte ra stin si a te l s

83/53

nd Acu ic te iti s Pe ap rfo pe rat nd ed ix

Patient, (male/female), (n)

Patient (n) Percentage (%)

103

100

ap N o pe rm nd al ix

Table 1. Characteristics of patients with clinical symptoms of acute appendicitis

Figure 1. Characteristics of patients. 3% 3% Taenia Entamoeba subspecies histolytica

5% Iodamoeba butschlii

stool samples was 13 (38.2%) Giardia intestinalis, 8 (23.5%) Blastocystis hominis, 6 (17. 6%) Entamoeba coli, 2 (5.9%) Iodamoeba butschlii and 1 (2.9%) mature Taenia subspecies ring. Of the patients, 2 (5.9%) cases contained both Giardia intestinalis and Blastocystis hominis, and 1 (2.9%) case contained both Blastocystis hominis and Entamoeba coli. Only 1 (2.9%) case was positive in present study out of a total of 12 (8.8%) patients with diarrhea analyzed with ELISA technique for specific antigens for Entamoeba histolytica (Table 2, Fig. 1). The most prevalent intestinal parasite in stool analysis was Giardia intestinalis, and this result was statistically significant (p<0.001). Pathological examination of appendectomy specimens showed that only 2 (1.47 %) cases contained parasites (1 Enterobius vermicularis, 1 Taenia subspecies). The patient with Taenia subspecies in appendectomy specimen also exhibited same parasite in preoperatively collected stool sample, but patient with Enterobius vermicularis in ap-

19% Entamoeba coli

40% Giardia Intestinalis

30% Blastocystis hominis

Figure 2. Shows ratios and species of the intestinal parasites that obtained from pre-operative stool samples.

pendectomy specimen did not exhibit any parasite in stool sample.

Table 2. Shows number and species of the intestinal parasites with clinical symptoms of acute appendicitis obtained from pre-operative stool samples Parasites

Frequency (n=34)

p

n %

Giardia intestinalis

13 38.2 <0.001

Blastocystis hominis

8 23.5

Entamoeba coli

6 17.6

Iodamoeba butschlii

2 5.9

Taenia subspecies

1

Entamoeba histolytica

1 2.9

2.9

Giardia intestinalis and Blastocystis hominis 2 5.9 Blastocystis hominis and Entamoeba coli.

1

2.9

34 (25%) of cases had intestinal parasites. Of these 34 patients, the incidence of intestinal parasites in stool samples was 13 (Giardia Intestinalis, 8 Blastocystis hominis, Entamoeba coli, Iodamoeba butschlii and mature Taenia subspecies (spp.) ring. Of the patients, cases contained both Giardia intestinalis and Blastocystis hominis, and 1 (2.9%) case contained both Blastocystis hominis and Entamoeba coli.

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Hatipoğlu et al. Pre-operative stool analysis for intestinal parasites and fecal occult blood in patients with acute appendicitis

Table 3. Shows fecal occult blood test ratios of operated patients with clinical symptoms of acute appendicitis

Fecal occult blood test

Total (n=136)

p

Negative Positive

n % n % n %

Acute appendicitis

93

90.2

10

9.7

103

75.7

Perforated appendicitis 7 46.7 8 53.3 15 11.1 <0.001 Normal appendix

16 88.9 2 11.1 18 13.2

Stool analysis also revealed that 14.7% (n=20) of patients had positive FOBT. Those with positive FOBT represented 9.7% (n=10) of 103 patients with AA, 53.3 (n=8) of 15 patients with PA, and 11.1% (n=2) of 18 patients with NA, and this was statistically more significant for PA than other groups (p<0.001) (Table 3).

DISCUSSION Parasitic diseases of GI tract affect more than half of the world population. While they are mainly observed in tropical countries, they have begun to become an important health problem in developing countries due to climatic conditions, excessive population growth, low level of education, failure to observe personal hygiene, inadequate and/or contaminated water sources, lack of infrastructure, increasing migration, and travel.[2,9–14,16,17] Intestinal parasites are more frequent in rural territories than urban cities.[17] Training and hygiene are very important for protection from infections that spread by fecal-oral route. Primary pathogenic event in majority of patients with AA is believed to be luminal obstruction. This event may result from a variety of causes, which include fecaliths, lymphoid hyperplasia, vegetable matter and fruit seeds, foreign bodies, intestinal parasites, barium from previous radiographic studies, and both primary (carcinoid, adenocarcinoma, Kaposi sarcoma, and lymphoma) and metastatic (colon and breast) tumors.[13,16,18] Lymphoid hyperplasia and fecaliths are the most frequently observed etiologies of luminal obstruction.[19] There is little evidence regarding the relationship between parasites and AA.[13] Presence of parasites in appendix may cause appendicitis, explained by hypothesis of appendiceal lumen obstruction. However, parasites can lead to AA, as do bacteria and viruses. According to the literature, parasitic infections such as enterobiasis,[5,6] taeniasis,[12,20–22] and ascariasis,[15,23] which are among the less frequent factors, have been observed in patients with AA. Geographic location and social situations lead to prominent variations in prevalence of parasites. Another factor in prevalence of parasites might be existence of minimal differentiations in techniques followed by pathologists.[5] 474

In the present study, we observed that 34 patients had intestinal parasites. Most frequent parasite found was Giardia intestinalis, but only 2 parasites (1 Enterobius vermicularis and 1 Taenia subspecies) were obtained in appendectomy specimens. In patients undergoing or planning surgical treatment due to AA, evaluation for intestinal parasites is important and may aid in both etiological and medical treatment of these patients. In most cases, same intestinal parasites were not obtained in histopathological examination of appendicitis specimen and in patient pre-operative stool sample. For this reason, variety and frequency of parasites did not correlate with appendicitis specimen in current study, and it may be concluded that there is not any risk for AA caused by parasites obtained from stool samples. Diagnosis of parasitic infestation is generally achieved only after pathological examination of resected appendix. Only 2 of the AA patients had intestinal parasites observable in appendectomy specimens. Taenia subspecies was also obtained from pre-operative stool sample of patient whose appendectomy specimen showed that parasite; however, Enterobius vermicularis was not observed in stool sample of second patient taken before surgery.

Enterobius vermicularis is observed commonly in GI tract worldwide, and is considered to be the most common parasitic infection that may cause ileocolitis, enterocutaneous fistulas, urinary tract infections, mesenteric abscesses, salpingitis, and appendicitis (lymphoid hyperplasia to acute phlegmonous appendicitis, gangrenous appendicitis and peritonitis). Mature form of Enterobius vermicularis is most frequently observed in proximal section of ascending colon, cecum, appendix, and terminal ileum.[6,8,11,16] The link between Enterobius vermicularis and appendicitis was first determined in 1899, and incidence of Enterobius vermicularis in patients with symptoms of AA ranges from 0.2-41.8%.[2,5–8,11,15,24,25] This infection is observed in all ages and socio-economic levels, and diagnosis may be determined by direct visualization of adult worms or microscopic detection of eggs, but only minorities of patients have eggs in their stool.[8] Enterobius vermicularis wanders widely inside the bowel, including appendix. Diagnosis of Enterobius vermicularis can be made using cellophane tape test, and treatment includes mebendazole and household sanitation.[7] In present study, we observed only 1 case of EnUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Hatipoğlu et al. Pre-operative stool analysis for intestinal parasites and fecal occult blood in patients with acute appendicitis

terobius vermicularis. This result was compatible with literature data but lower than expected. Cellophane tape test for diagnosis of Enterobius vermicularis could not be performed. Taeniasis in appendix is very rare, and there are few case reports about it in the literature.[8,21] Entry of Taenia subspecies into appendix remains an unsolved issue. Taeniasis is a well-known parasitic infection characterized by presence of Taenia saginata or Taenia solium in human intestines, and it occurs as result of consuming raw or undercooked meat. It is identified when segments of the parasite appear in stool or exit through anus.[8,10–12,16,21] In present study, eggs of Taenia subspecies were observed in 1 appendectomy specimen and 1 stool sample, although adult form of the parasite was not observed, and case was not specified as Taenia saginata or Taenia solium. Clinical symptoms of taeniasis are bowel irritation, abdominal pain, and diarrhea, and they may rarely lead to appendicitis or cholangitis.[16,26] The first sign of Taenia subspecies infection is usually a segment of parasite observed in stool by microscopy, and this infection of appendix is so rare that situation invites a case report.[11,20–22] Identification of specific species is not required in patients with taeniasis, and single dose of praziquantel or albendazole treatment can efficiently clear the infection following surgery.[11,16,17,20–22] Observation of intraluminal intestinal parasites within resected appendectomy specimen is generally an incidental finding, and roles of these parasites in AA have been discussed. Most parasitic appendix infestations are not associated with acute inflammation and are thus considered a component of false appendicitis. Intestinal parasites are commonly found within a non-inflamed appendix, and in some retrospective studies, they constitute only a minor percentage of negative appendectomies.[8] In the present study, low incidence of parasites among appendectomy specimens (1.47%) and failure to demonstrate a relationship with all events derived from appendicitis do not support hypothesis that intestinal parasites in stool analysis are a major cause of appendicitis. Parasites are rarely found in appendix, and their presence in stool analysis is very rarely associated with appendicitis. General surgeons should be aware that clinical management of such cases is different from management of non-parasitic appendicitis. Excisional appendectomy materials should be examined for fecaloid material, parasite eggs or intestinal parasite itself that might be within. Appendectomy treats only the symptoms and not the primary cause of the disease. Additionally, in acute appendicitis cases with parasitic infection, patient should receive post-operative anti-parasitic medical treatment to prevent possible re-infection. Moreover, family members should receive anthelmintic treatment to eliminate asymptomatic reservoirs and eradicate infections. FOB is defined as very small amounts of blood that may normally be lost from stomach or throughout the intestinal tract during digestion that are not detectable on gross inspection, Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

usually less than 50 mg of hemoglobin (Hg) per gram of stool. Increased amounts are associated with a variety of benign and malignant gastrointestinal diseases, especially colonic neoplasm, and tests are most often used to screen patients for such lesions. FOBT is based on detection of Hg in feces using guaiac-based technique, and newer technology and highly sensitive fecal immunochemical tests have also proved effective in screening for most common colorectal cancer.[27] No previous study in the literature investigating combination of appendicitis and FOBT has been located by current study authors as yet. It was current study finding that 14.7% of patients had positive FOBT, 53.3% of whom had PA. In PA cases, positive FOBT was statistically significant. This conduction may be explained by severe and long-term peri-appendicular colonic mucosal and sub-mucosal inflammation, with desquamation leading to mucosal hemorrhage.

Limitations Due to lack of patient compatibility and need for urgent operation, we could not use cellophane tape test for diagnosis of Enterebius vermicularis. Therefore, Enterebius vermicularis could not be discussed in this paper. Second, because intestinal parasites show presentation and frequency variation regionally in different age groups, there has not been any previous study investigating prevalence of intestinal parasites in authors’ region. Therefore, we could not compare AA cases with normal population prevalence. Third, stool analyses were performed during office hours because laboratory at study institution is open only at those times. Finally, relationship between positive FOBT and presence of intestinal parasites was not evaluated.

Conclusion Parasites are rarely found in the appendix, and their presence in stool analysis is very rarely associated with appendicitis. Appendectomy is not sufficient for curative treatment in parasitic infections with appendicitis. Medical treatment should also be administered after appendectomy. Intestinal parasites within resected appendix specimens are generally an incidental finding. Even if general surgeon does not observe inflamed appendix in course of operation, intestinal parasites should be considered an etiological factor for AA, especially in countries where intestinal parasites are endemic. Rapid screening of stool specimens by an experienced pathologist may be useful. A positive FOBT may be predictor for PA. Present study authors also believe that more comprehensive, randomized studies are needed to support our current findings. Conflict of interest: None declared.

REFERENCES 1. Hatipoglu S, Hatipoglu F, Abdullayev R. Acute right lower abdominal pain in women of reproductive age: clinical clues. World J Gastroenterol 2014;20:4043–9.

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Hatipoğlu et al. Pre-operative stool analysis for intestinal parasites and fecal occult blood in patients with acute appendicitis 2. da Silva DF, da Silva RJ, da Silva MG, Sartorelli AC, Rodrigues MA. Parasitic infection of the appendix as a cause of acute appendicitis. Parasitol Res 2007;102:99–102. 3. Ozcelik S, Sumer Z, Celiksoz A, Poyraz O, Koçoglu F, Demirtas S, et al. Survey of intestinal parasites in orphan of orphnage in Sivas, Turkey. Turkiye Parazitol Derg. 1995;19:257–9. 4. Dorfman S, Talbot IC, Torres R, Cardozo J, Sanchez M. Parasitic infestation in acute appendicitis. Ann Trop Med Parasitol 1995;89:99–101. 5. Gialamas E, Papavramidis T, Michalopoulos N, Karayannopoulou G, Cheva A, Vasilaki O, et al. Enterobius vermicularis: a rare cause of appendicitis. Turkiye Parazitol Derg 2012;36:37–40. 6. Sodergren MH, Jethwa P, Wilkinson S, Kerwat R. Presenting features of Enterobius vermicularis in the vermiform appendix. Scand J Gastroenterol 2009;44:457–61.

pendicitis in Nepal. Trop Doct 2006;36:160–2. 16. Ilhan E, Senlikci A, Kızanoglu H, Ustüner MA, Vardar E, Aykas A, et al. Do intestinal parasitic infestations in patients with clinically acute appendicitis increase the rate of negative laparotomy? Analysis of 3863 cases from Turkey. Prz Gastroenterol 2013;8:366–9. 17. Ulukanligil M, Seyrek A. Demographic and parasitic infection status of schoolchildren and sanitary conditions of schools in Sanliurfa, Turkey. BMC Public Health 2003;3:29. 18. Prystowsky JB, Pugh CM, Nagle AP. Acute appendicitis. Curr Probl Surg 2005;42:688–92. 19. Freeman HJ. Spontaneous free perforation of the small intestine in Crohn’s disease. Can J Gastroenterol 2002;16:23–7. 20. Dorfman S, Cardozo J, Dorfman D, Del Villar A. The role of parasites in acute appendicitis of pediatric patients. Invest Clin 2003;44:337–40.

7. Kucik CJ, Martin GL, Sortor BV. Common intestinal parasites. Am Fam Physician 2004;69:1161–8.

21. Hafezi Ahmadi M, Seifmanesh H. Taeniasis caused appendicitis without local tenderness: A rare case. Hospital Chronicles 2011;6:207–9.

8. Aydin O. Incidental parasitic infestations in surgically removed appendices: a retrospective analysis. Diagn Pathol 2007;2:16.

22. Ajmera RK, Simon GL. Appendicitis associated with Taenia species: cause or coincidental? Vector Borne Zoonotic Dis 2010;10:321–2.

9. Thanikachalam MP, Kasemsuk Y, Mak JW, Sharifah Emilia TS, Kandasamy P. A study of parasitic infections in the luminal contents and tissue sections of appendix specimens. Trop Biomed 2008;25:166–72.

23. Sforza M, Andjelkov K, Zaccheddu R, Ivanov D, Krstić S, Paganelli A. An unusual case of ascariasis of the appendix. Srp Arh Celok Lek 2011;139:809–11.

10. Meamar AR, Ahady N, Falakimoghaddam MH, Safari MR, Kia EB. Concomittant infection of appendix with Taenia and Enterobius vermicularis. J Med Sci 2006;6: 38–40.

24. Arca MJ, Gates RL, Groner JI, Hammond S, Caniano DA. Clinical manifestations of appendiceal pinworms in children: an institutional experience and a review of the literature. Pediatr Surg Int 2004;20:372–5.

11. Lejbkowicz F, Abel AB, Tsilman B, Cohen HI. Taenia infestation in the appendix: a report of two cases. J Med Microbiol 2002;51:90–1.

25. Saxena AK, Springer A, Tsokas J, Willital GH: Laparoscopic appendectomy in children with enterobiusvermicularis. Surg Laparosc Endosc Percutan Tech 2001;11:284–6.

12. Sartorelli AC, da Silva MG, Rodrigues MA, da Silva RJ. Appendiceal taeniasis presenting like acute appendicitis. Parasitol Res 2005;97:171–2. 13. Wani I, Maqbool M, Amin A, Shah F, Keema A, Singh J, et al. Appendiceal ascariasis in children. Ann Saudi Med 2010;30:63–6. 14. Madavo C, Hurriez H. Schistosomiasis of the appendix. J R Soc Med 2006;99:473–4. 15. Sah SP, Bhadani PP. Enterobius vermicularis causing symptoms of ap-

26. Kia EB, Afshar-Moghadam N, Kazemzade H. Appendicular taeniasis: association with acute gangrene appendicitis in Isfahan, Iran. South Asian J Trop Med Public Health 2004;35:259–61. 27. Young GP, Symonds EL, Allison JE, Cole SR, Fraser CG, Halloran SP, et al. Advances in Fecal Occult Blood Tests: the FIT revolution. Dig Dis Sci 2015;60:609–22.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisit hastalarında gaitada gizli kan ve intestinal parazitler için ameliyat öncesi gaita analizi Dr. Sinan Hatipoğlu,1 Dr. Uğur Lök,2 Dr. Umut Gülaçtı,2 Dr. Tuncay Çelik3 Adıyaman Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Adıyaman Adıyaman Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Adıyaman 3 Adıyaman Üniversitesi Tıp Fakültesi, Parazitoloji Anabilim Dalı, Adıyaman 1 2

AMAÇ: Akut apandisitin etiyolojisi nadir olarak gastrointesitinal sistemin parazitik enfeksiyonlarını içermektedir. Parazitler bazen histopatolojik inceleme sırasında lümen içinde gözlemlenebilmesine rağmen ameliyat öncesi tanısı zor bir durum olarak kalmaya devam etmektedir. Bu çalışmanın amacı, akut apandisitin klinik semptomları ile acil servise getirilen ve apendektomi yapılan hastalarda gaitada gizli kan, intestinal parazitlerin tür ve prevelansını ileriye yönelik olarak taramaktır. GEREÇ VE YÖNTEM: Haziran 2009 ile Aralık 2014 tarihleri arasında apendektomi geçiren 13 yaş üstü 136 hasta ileriye yönelik olarak ve tüm hastaların histopatolojik analiz verileri geriye dönük olarak değerlendirildi. BULGULAR: Apendektomi sonrası histopatolojik incelemede, hastaların %75.5 (n=103) akut apandisit (AA), %13.2’si negatif apandisit (normal appendiks, NA) (n=18), %11.1 (n=15) perfore apandisit (PA) idi. Ameliyat öncesi gaita analizinde, tüm hastaların %25’inde (n=34) intestinal parazitlerin var olduğu, %14.7’sinde (n=20) gaitada gizli kanın pozitif olduğu görüldü. Akut apandisit olgularının %9.7’sinde (n=10), PA olgularının %53.3’ünde (n=8) ve NA olgularının %11.1’inde (n=2) gaitada gizli kan pozitifliği tespit edildi ve PA olgularındaki gaitada gizli kan pozitifliği anlamlı derecede yüksek idi (p<0.001). TARTIŞMA: Gaitada intestinal parazitler, apandisit ile ilişkili olmayabilir fakat apandisitin patolojik bulgularına sıklıkla yol açarlar. Gaitada gizli kan pozitifliği apandisit perforasyonu için önemli bir kanıt olabilir. Anahtar sözcükler: Apandisit; gaita analizi; gaitada gizli kan; intestinal parazitler. Ulus Travma Acil Cerrahi Derg 2016;22(5):471–476

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ORIGIN A L A R T IC L E

How safe is the semi-sterile technique in the percutaneous pinning of supracondylar humerus fractures? Ali Turgut, M.D., Burak Önvural, M.D., Cemal Kazımoğlu, M.D., Tayfun Bacaksız, M.D., Önder Kalenderer, Haluk Ağuş, M.D. Department of Orthopaedics and Traumatology, Tepecik Training and Research Hospital, İzmir-Turkey

ABSTRACT BACKGROUND: The purpose of the present study was to evaluate safety and efficiency of the semi-sterile technique used in recent years in treatment of pediatric supracondylar humeral fractures (SHF). METHODS: Total of 712 patients who were treated for SHF via closed reduction and percutaneous fixation with semi-sterile technique were enrolled in present study. Patients were evaluated for postoperative infection and other complications. Clinical and radiological assessments were also made. RESULTS: It was found that there were 52 (7.3%) pin tract infections, which responded to oral antibiotic administration and pin care without need for early pin removal (before 3 weeks). There were no deep infections. Loss of reduction was observed in 82 patients (11.5%). There were 59 iatrogenic nerve injuries (8.3%), of which 52 (7.3%) were ulnar palsy. Clinically apparent cubitus varus was observed in 29 (4.1%) patients. CONCLUSION: Though semi-sterile technique is an effective treatment in closed percutaneous pinning of SHF, increased pin tract infection risk is a matter of concern. Keywords: Pin tract infection; semi-sterile technique; supracondylar humerus fracture.

INTRODUCTION Supracondylar humeral fractures (SHF) are the most common elbow fractures in children.[1] Current treatment choice for supracondylar fractures is closed reduction and percutaneous pin fixation with fluoroscopic guidance.[2–6] Semi-sterile pin fixation technique has been reported as alternative treatment modality that saves time, costs, and materials without resulting increased infection risk.[7] Bashyal et al. concluded that limited preparation with towel draping to treat SHF has low infection rate. It was stated that neither full preparation and draping nor preoperative prophylactic antibiotic administration seems to be advantageous.[8] Address for correspondence: Ali Turgut, M.D. Tepecik Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İzmir, Turkey Tel: +90 232 - 444 35 60 E-mail: draliturgutort@yahoo.com.tr Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):477–482 doi: 10.5505/tjtes.2016.31614 Copyright 2016 TJTES

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Though full surgical preparation and draping is thought to be standard care, studies are encouraging use of semi-sterile technique because of the savings it offers. Our hospital is a referral center for pediatric trauma patients, especially outside of typical work hours. Preference is to operate on SHF as an urgent case as soon as possible. Some nights, 5 or 6 patients may require surgery. Heavy workload of hospital surgical department makes saving time very important. Semisterile surgical technique has been in use at our hospital since 2008. Present study was designed to determine if semi-sterile technique is really as safe as has been reported by conducting retrospective review of efficacy and safety of semi-sterile pin fixation technique in treatment of SHF in children.

MATERIALS AND METHODS Retrospective analysis of database of patients treated for SHF in our training and research hospital between January 2009 and December 2013 was performed. More reliable digital archive of hospital available as of 2009 determined earliest records used. Study was approved by local ethics committee (12.05.2015/number:4). Inclusion criteria were skeletal immaturity, at least 6 months of follow-up, and treatment using 477


Turgut et al. How safe is the semi-sterile technique in the percutaneous pinning of supracondylar humerus fractures?

closed reduction and percutaneous pinning (CRPP). Exclusion criteria were open fracture, necessity for open surgery, ipsilateral fracture, or flexion-type fracture pattern. Of initial total of 767 patients, 7 patients had open fractures, 5 required open reduction, 17 had flexion-type injury, 4 patients had ipsilateral distal radius fracture, and 22 patients were lost to follow-up before pin removal and therefore excluded. The present study is an evaluation of data of 712 patients. Preoperative and follow-up radiographs of patients were reviewed to determine type of fracture, treatment type (lateral or cross-pinned) and Baumann angle[9] measurement. Outpatient clinic records were evaluated for follow-up duration, length of hospitalization, iatrogenic nerve injuries, patient complaints, deformity, pin site infection and treatment, and physical examination notes.

Surgical Technique and Postoperative Care Ketamine (Ketalar®) anesthesia was used for all patients, and all were in supine position on operating table. All procedures were performed by a senior resident and a mid-level (more than 1 year in training) resident under guidance of surgeon. Fracture was reduced by one of the residents with guidance of fluoroscopy (Figure 1a) while wearing non-sterile gloves. After confirmation of reduction, second resident maintained reduction and rotated arm internally to allow surgeon to pass Kirschner wires (K-wire) laterally while on image intensifier. If malrotation of fracture was present, it was corrected by second resident with internal rotation of proximal fragment. The first resident wore sterile gloves at this step and placed sterile towel and dressings on image intensifier. After selecting appropriate diameter of K-wire, first resident fastened it

(a)

(d)

(b)

to the drill. Beginning at lateral epicondyle, 10% povidone-iodine solution was applied in ever-widening circles until circle of at least 5 cm in diameter was saturated (Figure 1b). Iodine solution was allowed to dry on skin for at least 1 minute. Two K-wires were passed laterally under fluoroscopic guidance (Figure 1c). Two lateral K-wires were used in parallel if third K-wire was used medially to prevent rotation of distal fragment. If fracture was Type II and only lateral fixation was required, K-wires were passed in divergent fashion. If crossed pin configuration was used, same protocol was applied at medial side of elbow using medial epicondyle as reference point for the circle (Figure 1d). Single wire was then passed medially with lessening flexion of elbow to minimize anterior subluxation of ulnar nerve (Figure 1e). One of laterally inserted wires was removed if fracture was thought to be stable. Final position of fixed fracture was confirmed (Figures 2a and b). All patients received single dose of prophylactic antibiotic regimen before procedure (cefazolin sodium [Cefozin®] 25 mg/kg, intravenously). Pins were left protruding through skin with bent end for easy removal. Long arm cast with approximately 70° to 90° of elbow flexion or splint was applied in operating room. Patients did not receive antibiotics after surgery and antibiotic medication was not prescribed after hospital discharge. Parents of patients were told to visit family physician in every 4 days for pin site care until pins were removed. Postoperative clinical and radiographic evaluations were performed at 1 week, 3 to 4 weeks, and 3 months. Cast and pins were removed at third or fourth week follow-up as outpatient procedure according to radiological indication of

(c)

(e)

Figure 1. (a) Reduction of the fracture with non-sterile gloves. (b) Preparation of lateral side of the elbow with povidon-iodine. (c) Passing Kirschner wires laterally. (d) Preparation of medial side of the elbow with povidon-iodine. (e) Passing Kirschner wire medially.

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(a)

SPSS software (version 21.0; SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Patients were divided into 2 groups according to fracture type (type II or type III-IV), pin configuration (only laterally or cross-pinned) and gender (male or female). Complication rates of groups were compared using chi-squared test and p<0.05 was considered statistically significant.

(b)

RESULTS Mean follow-up of patients was 23.6 months (range: 6–44 months). Average hospitalization period was 2 days (range: 1–6 days). Patient demographic and fracture- related data are presented in detail in Table 1. Pin tract infections, which responded well to oral antibiotic treatment and local pin site care without requiring early pin removal, occurred in 52 (7.3%) patients. There was no deep infection (serious discharge and localized erythema) or osteomyelitis (Table 2). There was no reoperation for loss of reduction or other reason. Based on criteria of Flynn et al., 8 patients (1.12%) had fair or poor result due to varus angulation, with excellent functional outcome in 6. Two patients with fair results had significant loss of range of motion at final follow-up; 82 (11.5%) patients had reduction loss in coronal plane at final follow-up. There was no incidence of loss of reduction in sagittal plane. Among those with reduction loss in coronal plane, only 29 patients had clinically noticeable cubitus varus deformity. Average change in Baumann angle was 2.5° (range: 0–5°). No patient had major loss of reduction; greatest dif-

Figure 2. (a) Antero-posterior fluoroscopy view of the reduced and fixed fracture. (b) Lateral fluoroscopy view of the reduced and fixed fracture.

fracture healing. Humeral-ulnar carrying angle was evaluated radiologically, and clinical assessment was made for flexion and extension degree according to Flynn’s criteria.[10] Patient’s uninjured side was compared with injured site radiologically and clinically at 6-month intervals. Baumann angle of intraoperative or immediate postoperative anteroposterior radiograph was compared with angle on radiograph taken at time of fracture union (approximately third week) to determine any reduction loss. Any degree of difference in this angle was accepted as loss of reduction in coronal plane. Failure of anterior humeral line to intersect capitellar physis was accepted as loss of reduction in sagittal plane.

Table 1. Patient demographic and fracture-related data Fracture type

II

III

IV

Total

n % n % n % n %

Gender of patients Male

222 55

151 56

29 61

402 56.5

Female

176 45

116 44

18 39

310 43.5

Number of patients

398

267

47

712

56

37.5

6.5

100

Table 2. Total complications Complication

Number of patients

Ratio (%)

Loss of reduction

82

11.5

Clinically apparent cubitus varus

29

4.1

Superficial/pin site infection

52

7.3

Deep ınfection/osteomyelitis Iatrogenic nerve injury (sensorial or motor)

Ulnar nerve

52

Median nerve

4

Radial nerve

3

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7.3 0.6

0.4

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Table 3. Statistical analysis of each complication according to group

Pin tract p* Cubitus p* Loss of p* Ulnar nerve p* Median nerve p* Radial nerve p* infection varus reduction injury injury injury (n/n) (n/n) (n/n) (n/n) (n/n) (n/n)

Type II

18/34 0.001 7/22 <0.001 18/64 <0.001 9/43 <0.001 1/3 0.21 2/1 0.70

fracture/type III–IV fracture (398/314) Laterally

9/43 0.14 7/22 0.83 14/68 0.54 0/52 <0.001 1/3 0.96 0/3 0.30

pinned/crosspinned (184/528) Male/female

25/27 0.32 17/12 0.81 41/41 0.21 28/24 0.49 2/2 0.32 1/2 0.58

(402/310) *Chi-squared test.

ference between perioperative and final Baumann angle was 5°. There was total of 59 nerve injuries (52 ulnar, 4 median, 3 radial nerve) in 57 patients (8.0%) that were not recorded preoperatively. Crossed pin configuration was used in all patients who had ulnar nerve injury (52 of 590 patients [8.8%]). K-wires were removed after confirmation of fracture healing, including patients with iatrogenic ulnar nerve injury. All ulnar nerve injuries recovered without any further treatment in average of 2½ months (range: 1–7 months). There were 398 patients with type II fracture and 314 patients with type III or type IV fracture. Fractures were pinned only laterally in 184 patients who had type II fracture. Pin tract infection, loss of reduction, cubitus varus deformity, and iatrogenic ulnar nerve injury complication ratios were statistically significantly higher in patients with type III or type IV fracture (p=0.001, <0.001, <0.001, <0.001, respectively). Iatrogenic ulnar nerve injury was also statistically significantly higher in cross-pinned group, as expected (p=<0.001) (Table 3). There was no significant difference in complication rate according to patient gender.

DISCUSSION Iobst et al. were first to report that semi-sterile technique was safe and efficient method in a study with 304 consecutive patients. Authors stated that procedure is very safe with regard to infection risk, reporting no patients with superficial or deep infections. Present series includes more than double the number of patients compared to Lobst study. Superficial infection rate of 7.22% was observed, which is considerably higher than less than 1 and 6% reported in current literature, which adds to risk of infection.[11–16] From an observational point of view, authors acknowledge that many parents of our patients are not precise in following recommendations for pin tract care following K-wire fixation; however, this is not enough to explain high superficial infection rate in present series. It is thought that it may be attributed at least partially to semi-sterile technique. 480

Despite fact that all infections were brought under control without serious complications, for medical and legal reasons, surgeons should be aware of high superficial infection rates. Fowles et al.[17] reported approximately 3% significant infection requiring more than oral antibiotic treatment in their series. Deep infection or septic arthritis is devastating complication after pin tract infection, and may lead to serious consequences. Condition of operating room and education of personnel are important issues that must be keep in mind during semi-sterile pin application, especially in developing countries. Iobst et al. described procedure as similar to setup used for placing traction pin at bedside. However, it is important to be aware that pins used for supracondylar fracture directly encounter fracture hematoma several times, jeopardizing the procedure. Therefore, authors do not agree that perioperative antibiotics in association with percutaneous pinning of supracondylar humerus fractures are not necessary. Pin tract infections were significantly lower in patients with relatively less unstable fractures in present study group. Surgery duration was not included in hospital records, but it is thought that duration of pinning of unstable fracture is longer. Therefore, higher infection rates may be due in part to prolonged length of procedure. We found no significant difference in infection rate according to pin configuration in present study group. Literature information about pin site infection is primarily based on retrospectively designed studies using recorded physical examination notes, as present study did. In a very recent study, Kao et al.[18] prospectively compared daily pin care and no pin care in patients with SHF who were treated using CRPP. Method of skin preparation was not mentioned, but it was stated that all patients received prophylactic antibiotic cefazolin sodium 30 mg/dL. Interestingly, pin site infections, which were mostly low grade, were reported in 53.3% of non-care group patients and 90.3% of daily care group Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Turgut et al. How safe is the semi-sterile technique in the percutaneous pinning of supracondylar humerus fractures?

patients. Given these findings, it would seem that perhaps physical examination records are not being kept adequately. Injury to ulnar nerve has been reported to range from 1.4% to 20%.[19] Lyons et al.[20] and Kalenderer et al.[21] reported 5% and 5.2% iatrogenic ulnar nerve injuries in 375 and 473 patients, respectively. Iobst et al.[7] reported nerve injuries in 20 patients (6.6%) they treated with semi-sterile technique. In present study, iatrogenic ulnar nerve injury was observed in 7.3% (52/712) of patients. It is the opinion of the authors that this could be minimalized if mini-open technique described by Green et al.[22] is used, but it is inappropriate to use this technique in semi-sterile conditions. Shtarker et al.[19] used ulnar nerve monitoring to avoid iatrogenic nerve injury for medial pin insertion and stated that there were no iatrogenic ulnar nerve injuries in 138 patients. Similarly, nerve monitoring is not appropriate for semi-sterile conditions. It is a drawback of semi-sterile technique. Flexion of elbow was reduced and K-wire was inserted from medial epicondyle instead of ulnar groove to minimize risk of iatrogenic injury in present study patient group.

dylar fractures to advanced facilities or trauma centers has become a trend in recent years. As a result, large hospitals have a workload beyond their capacity. Semi-sterile technique provides means to operate on supracondylar fractures as emergency case in these busy centers. As open surgery for supracondylar fractures is rarely performed in our clinic, semi-sterile technique is very practical and suitable method. Procedure is significantly quicker and less expensive than full sterile preparation of patient. There are several limitations to this study. Study design is retrospective; confounding factors and cost analysis, which would be more valid in control-based analysis, were not studied; and surgery duration data could not be evaluated. In conclusion, semi-sterile technique is an alternative treatment modality in management of SHF in children; however, substantial increase in superficial pin tract infections is a concern. Patients must be strictly monitored if this technique is preferred. Conflict of interest: None declared.

Loss of reduction has been reported in 20–30% of conservatively treated type II and III SHF and 2.9–18.2% of surgically treated patients.[1,23] Sankar et al. stated that loss of reduction can be expected if bicortical fixation of 2 or more pins is not achieved, if there is inadequate pin separation (>2 mm) at fracture site, or if 2 or more wires do not pass through both fragments.[24] In a very recent study, Pennock et al.[25] concluded that primary factor responsible for loss of reduction is inadequate pin separation. It was recommended that there be at least 13 mm between wires, or one-third of width of humerus at level of fracture. Reduction loss was observed in 11.5% of patients in present study. This ratio is higher than many previously published data.[1,24,25] Use of any change of Baumann angle as criterion for loss of reduction likely explains high rate, since all instances of loss of reduction were mild (less than 5° in Baumann angle). Higher rate of loss of reduction in patients with type III and IV fractures is probably due to comminution of fracture or lack of stability obtained with intact periosteum. The most common deformity following SHF is cubitus varus. Commonly accepted criteria for significant coronal plane deformity is change of >12° in Baumann angle.[26] Clinically apparent cubitus varus deformity was observed in 29 patients (4.1%) in present study. As greatest change in Baumann angle was 5° in present study group, it is thought that intraoperative reduction in these 29 patients was due to prior varus position. Tellisi et al. reported up to 6.6% cubitus varus deformity.[27] In a recent study, Or et al.[26] stated that they had observed malalignment in 20 out of 396 (5.05%) patients. Present study results are compatible with the literature. Present study authors now annually treat more than 200 supracondylar fractures surgically. Transferring supraconUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5

REFERENCES 1. Zorrilla S de Neira J, Prada-Cañizares A, Marti-Ciruelos R, PretellMazzini J. Supracondylar humeral fractures in children: current concepts for management and prognosis. Int Orthop 2015;39:2287–96. 2. Bombaci H, Gereli A, Küçükyazici O, Görgeç M, Deniz G. The effect of surgical exposure on the clinic outcomes of supracondylar humerus fractures in children. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2007;13:49–54. 3. Herring JA. Upper extremity injuries. In: Herring JA, ed. Tachdjian’s Pediatric Orthopaedics. Philadelphia, PA: W.B. Saunders 2002:2139–68. 4. Kasser JR, Beaty JH. Supracondylar fractures of the distal humerus. In: Beaty JH, Kasser JR, eds. Fractures in Children. Philadelphia, PA: Lippincott Williams & Wilkins 2001:577Y624. 5. de las Heras J, Durán D, de la Cerda J, Romanillos O, Martínez-Miranda J, Rodríguez-Merchán EC. Supracondylar fractures of the humerus in children. Clin Orthop Relat Res 2005;432:57–64. 6. Kazimoglu C, Cetin M, Sener M, Aguş H, Kalanderer O. Operative management of type III extension supracondylar fractures in children. Int Orthop 2009;33:1089–94. 7. Iobst CA, Spurdle C, King WF, Lopez M. Percutaneous pinning of pediatric supracondylar humerus fractures with the semisterile technique: the Miami experience. J Pediatr Orthop 2007;27:17–22. 8. Bashyal RK, Chu JY, Schoenecker PL, Dobbs MB, Luhmann SJ, Gordon JE. Complications after pinning of supracondylar distal humerus fractures. J Pediatr Orthop 2009;29:704–8. 9. Baumann E. On the treatment of fractures of the elbow joint. [Article in German] Langenbecks Arch Klin Chir Ver Dtsch Z Chir 1960;295:300– 4. [Abstract] 10. Flynn JC, Matthews JG, Benoit RL. Blind pinning of displaced supracondylar fractures of the humerus in children. Sixteen years’ experience with long-term follow-up. J Bone Joint Surg Am 1974;56:263–72. 11. Reynolds RA, Mirzayan R. A technique to determine proper pin placement of crossed pins in supracondylar fractures of the elbow. J Pediatr Orthop 2000;20:485–9.

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Turgut et al. How safe is the semi-sterile technique in the percutaneous pinning of supracondylar humerus fractures? 12. Ponce BA, Hedequist DJ, Zurakowski D, Atkinson CC, Waters PM. Complications and timing of follow-up after closed reduction and percutaneous pinning of supracondylar humerus fractures: follow-up after percutaneous pinning of supracondylar humerus fractures. J Pediatr Orthop 2004;24:610–4. 13. Shannon FJ, Mohan P, Chacko J, D’Souza LG. “Dorgan’s” percutaneous lateral cross-wiring of supracondylar fractures of the humerus in children. J Pediatr Orthop 2004;24:376–9. 14. Skaggs DL, Cluck MW, Mostofi A, Flynn JM, Kay RM. Lateral-entry pin fixation in the management of supracondylar fractures in children. J Bone Joint Surg Am 2004;86:702–7. 15. Topping RE, Blanco JS, Davis TJ. Clinical evaluation of crossed-pin versus lateral-pin fixation in displaced supracondylar humerus fractures. J Pediatr Orthop. 1995;15:435–9. 16. Meyer CL, Kozin SH, Herman MJ, Safier S, Abzug JM. Complications of pediatric supracondylar humeral fractures. Instr Course Lect 2015;64:483–91. 17. Fowles JV, Kassab MT. Displaced supracondylar fractures of the elbow in children. A report on the fixation of extension and flexion fractures by two lateral percutaneous pins. J Bone Joint Surg Br 1974;56:490–500. 18. Kao HK, Chen MC, Lee WC, Yang WE, Chang CH. A prospective comparative study of pin site infection in pediatric supracondylar humeral fractures: daily pin care vs. no pin care. Arch Orthop Trauma Surg 2014;134:919–23. 19. Shtarker H, Elboim-Gabyzon M, Bathish E, Laufer Y, Rahamimov N, Volpin G. Ulnar nerve monitoring during percutaneous pinning of supracondylar fractures in children. J Pediatr Orthop 2014;34:161–5.

20. Lyons JP, Ashley E, Hoffer MM. Ulnar nerve palsies after percutaneous cross-pinning of supracondylar fractures in children’s elbows. J Pediatr Orthop 1998;18:43–5. 21. Kalenderer O, Reisoglu A, Surer L, Agus H. How should one treat iatrogenic ulnar injury after closed reduction and percutaneous pinning of paediatric supracondylar humeral fractures? Injury 2008;39:463–6. 22. Green DW, Widmann RF, Frank JS, Gardner MJ. Low incidence of ulnar nerve injury with crossed pin placement for pediatric supracondylar humerus fractures using a mini-open technique. J Orthop Trauma 2005;19:158–63. 23. Balakumar B, Madhuri V. A retrospective analysis of loss of reduction in operated supracondylar humerus fractures. Indian J Orthop 2012;46:690–7. 24. Sankar WN, Hebela NM, Skaggs DL, Flynn JM. Loss of pin fixation in displaced supracondylar humeral fractures in children: causes and prevention. J Bone Joint Surg Am 2007;89:713–7. 25. Pennock AT, Charles M, Moor M, Bastrom TP, Newton PO. Potential causes of loss of reduction in supracondylar humerus fractures. J Pediatr Orthop 2014;34:691–7. 26. Or O, Weil Y, Simanovsky N, Panski A, Goldman V, Lamdan R. The outcome of early revision of malaligned pediatric supracondylar humerus fractures. Injury 2015;46:1585–90. 27. Tellisi N, Abusetta G, Day M, Hamid A, Ashammakhi N, Wahab KH. Management of Gartland’s type III supracondylar fractures of the humerus in children: the role audit and practice guidelines. Injury 2004;35:1167–71.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Suprakondiler humerus kırıklarının perkütan tellenmesinde kısmi steril teknik ne kadar güvenlidir? Dr. Ali Turgut, Dr. Burak Önvural, Dr. Cemal Kazımoğlu, Dr. Tayfun Bacaksız, Dr. Önder Kalenderer, Dr. Haluk Ağuş Tepecik Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İzmir

AMAÇ: Kısmi steril teknik, çocuk suprakondiler humerus kırıklarının tedavisinde son yıllarda kullanılır hale gelmiştir. Bu çalışmanın amacı bu tekniğin suprakondiler humerus kırıklarının tedavisindeki güvenilirlik ve etkinliğinin araştırılmasıdır. GEREÇ VE YÖNTEM: Bu çalışmaya, kısmi steril teknik kullanılarak kapalı redüksiyon ve fiksasyon uygulanan 712 hasta dahil edildi. Hastalar ameliyat sonrası oluşabilecek olan enfeksiyon ve diğer komplikasyonlar açısından değerlendirildi. Klinik ve radyolojik değerlendirmeler yapıldı. BULGULAR: Elli iki hastada (%7.22), ağızdan antibiyotik tedavisi ve tel dibi bakımına cevap veren erken tel çekilmesini (üç hafta öncesi) gerektirmeyen çivi yolu enfeksiyonu izlendi. Derin enfeksiyon ile karşılaşılmadı. Redüksiyon kaybı ile 82 hastada (%11.5) karşılaşıldı. Elli iki tanesi (%7.3) ulnar sinir olmak üzere toplam 59 (%8.3) iyatrojenik sinir yaralanması oluştu. Yirmi dokuz (%4.1) hastada klinik olarak belirgin kubitus varus deformitesi vardı. TARTIŞMA: Kısmi steril teknik suprakondiler humerus kırıklarının tedavisinde etkiliymiş gibi görünmekteyse de artmış tel dibi enfeksiyon oranları kaygı vericidir. Anahtar sözcükler: Kısmi steril teknik; suprakondiler humerus kırıkları; tel dibi enfeksiyonu. Ulus Travma Acil Cerrahi Derg 2016;22(5):477–482

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ORIGIN A L A R T IC L E

Comparison of lateral versus triceps-splitting posterior approach in the surgical treatment of pediatric supracondylar humerus fractures Faik Türkmen, M.D.,1 Serdar Toker, M.D.,1,2 Kayhan Kesik, M.D.,1 İsmail Hakkı Korucu, M.D.,1 Mehmet Ali Acar, M.D.,3 1

Department of Orthopaedics and Traumatology, Necmettin Erbakan University Meram Faculty of Medicine, Konya-Turkey

2

Department of Hand and Upper Extremity Surgery Division, Necmettin Erbakan University Meram Faculty of Medicine, Konya-Turkey

3

Department of Orthopaedics and Traumatology, Selçuk University Faculty of Medicine, Konya-Turkey

ABSTRACT BACKGROUND: Supracondylar humerus fracture is the most common fracture of the elbow in children. Closed reduction and percutaneous pinning is considered to be the optimal treatment strategy; however, in some instances, open reduction may be necessary. The aim of this retrospective study was to compare clinical and functional results of triceps-splitting posterior versus lateral approach in pediatric supracondylar humerus fracture surgery. METHODS: A total of 38 patients underwent surgery; Group 1 consisted of 30 patients on whom posterior approach was used, while lateral approach was used on the 8 patients in Group 2. Flynn criteria were used to evaluate cosmetic and clinical results. Fracture healing was assessed with anteroposterior and lateral x-rays. Patients and parents were asked to describe time needed for complete return of full elbow range of motion (ROM) and overall satisfaction. RESULTS: Mean fracture union time was 44.1 days and 46.3 days, and time required to regain complete or near complete elbow ROM was 57.5 days and 55.7 days after splint removal for Group 1 and Group 2, respectively. Twenty-one of 30 (70%) patients (and parents) in Group 1, and 6 of 8 (75%) patients (and parents) in Group 2 were totally satisfied with the results. Twenty-one of 30 (70%) patients in Group 1, and 6 of 8 (75%) patients in Group 2 had excellent cosmetic and functional results according to Flynn outcome criteria. CONCLUSION: In cases of pediatric supracondylar humerus fracture, early closed reduction and percutaneous pinning is preferred; however, when this method is not applicable, triceps-splitting posterior approach is a safe and comparable method to lateral approach with advantages of easier fracture reduction and shorter operating time. Keywords: Posterior approach; supracondylar humerus fracture; triceps.

INTRODUCTION Supracondylar humerus fracture is the most common fracture encountered in children.[1–3] Closed reduction and percutaneous pinning is considered the Address for correspondence: Faik Türkmen, M.D. Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, 42090 Konya, Turkey Tel: +90 332 - 223 62 30 E-mail: turkmenfaik@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):483–488 doi: 10.5505/tjtes.2016.74606 Copyright 2016 TJTES

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optimal treatment for most supracondylar fractures.[4] However, open reduction may be necessary in cases of irreducible fragments, open fractures, or when there is neurovascular injury.[5–7] Lateral, medial, or posterior approach may be used. [8] Posterior approach is an easy approach, but it is not usually recommended due to complications such as osteonecrosis of the trochlea[2] or stiffness due to wide dissection.[9,10] Some authors, however, have stated that there was no significant difference in clinical results.[11] The aim of this retrospective study was to compare the clinical and functional results of posterior versus lateral approach in surgical treatment of pediatric supracondylar humerus fracture.

MATERIALS AND METHODS The institutional review board approved the chart review for this study, and informed consent was obtained from all pa483


Türkmen et al. Lateral versus posterior approach for pediatric supracondylar humerus fractures

tients. Medical records of 138 children with supracondylar humerus fracture who were operated on at the institution between January 2008 and November 2013 were retrospectively reviewed. Patients with Gartland Type III fractures[12] who underwent open reduction with either posterior or lateral approach and cross-pin fixation were included in the study. Exclusion criteria were open fracture or fracture of the ipsilateral upper limb, inadequate radiographs, incomplete data, or loss to follow-up. A total of 38 patients (23 boys and 15 girls) matched these criteria. Mean age of patients at the time of surgery was 7.8 years (range: 5.1–12.7 years), and mean follow-up time was 4.2 years (range: 1.4–7.2 years) (Table 1). All patients underwent surgery on the day of fracture under general anesthesia and in a supine position. Approach was chosen based on the surgeon’s experience. For posterior approach, after application of tourniquet, a 5 cm skin incision was made beginning 2 cm superior to olecranon and extending proximally on midline of the arm. Triceps fascia was cut and bone exposed by splitting triceps muscle on midline. Reduction of fracture under direct visualization was followed by repair with 2 or 3 cross K-wires, 1 or 2 from lateral epicondyle and 1 from medial epicondyle (Fig. 1a, b). Triceps muscle and fascia were repaired with 4 to 5 interrupted absorbable sutures and then skin was closed. Long arm splint was applied for 4 weeks. Pins were extracted in the clinic 2 weeks after splint removal. For lateral approach, a 4 to 5 cm skin incision over lateral bony prominence was made and fracture was exposed, but since direct visualization in this approach was not complete (Fig. 3), indirect fracture reduction was performed by manipulation with fingers and tools. For medial pin inser-

(a)

Table 1. Demographic data of the groups Groups

Group1 Group2

Number of patients

30

8

Mean age (years)

7.8

7.9

Girl/boy ratio

12/18

3/5

Mean follow-up time (months)

50.32

50.41

tion, a 2 cm incision was made on medial epicondyle, condyle was exposed, and pin was placed directly in the humerus in order to protect ulnar nerve. Remainder of operation and follow-up period was the same as for posterior approach. Patient outcomes were evaluated using Flynn criteria[5] at final follow-up visit (Table 2). Complications such as reduction loss, pin migration, infection, osteonecrosis of any part of the elbow, bone healing, and functional results were evaluated. Plain anteroposterior and lateral radiographs of the elbow taken on first postoperative day and date of pin removal were used to assess loss in reduction (Figs. 2a, b and 3a, b). Patients and parents were also asked about overall satisfaction. Statistical methods designed for independent observations were used. Mean and standard deviation were calculated. Non-continuous variables were compared using chi-square test, and Spearman’s correlation analysis was applied to test associations of variables. Relationship between clinical outcome and range of motion (ROM) at final follow-up were evaluated with Mann-Whitney U test. All analyses were per-

(b)

Figure 1. (a, b) Anteroposterior and lateral view of the left elbow of a 9-year-old girl with a supracondylar humerus fracture that occurred in a fall on outstretched hand and extended elbow.

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(a)

(b)

(a)

(b)

Figure 2. (a, b) Anteroposterior and lateral x-rays taken at the fourth week following surgery.

Figure 3. (a, b) Anteroposterior and lateral x-rays taken after pin extraction in the clinic at sixth week after surgery.

formed using SPSS statistical software (version 21.0; SPSS Inc., Chicago, IL, USA).

Mean splinting period was 31.97 days (range: 26–44 days) for Group 1, and 31.75 days (range: 24–41 days) for Group 2. The difference is not statistically significant (p<0.05).

RESULTS There were 36 Gartland type III fractures and 2 type II fractures in the study. No loss of reduction, pin migration, osteonecrosis, or nonunion was recorded. Superficial pin infection was noted in 3 patients: 2 patients in Group 1 and 1 patient in group 2, which were resolved with oral antibiotic treatment and saw no additional complication. All fractures healed uneventfully.

Pin removal took place upon fracture union. Mean fracture union time was 44.1 days and 46.3 days, and time for complete or near complete return of the elbow ROM was 57.5 days and 55.7 days after splint removal for Group 1 and Group 2, respectively. These differences were not statistically significant (p<0.05). Twenty-one of 30 (70%) patients (and parents) in Group 1,

Table 2. Flynn criteria[5] for grading results Results Rating

Cosmetic factor: Loss of carrying angle (degrees)

Satisfactory Excellent

Functional factor: Loss of motion (degrees)

0–5

0–5

Good

6–10

6–10

Fair

11–15

11–15

Unsatisfactory Poor

>15

>15

Table 3. Statistical analysis of differences between the 2 groups in length of time to achieve fracture union, patient and parent satisfaction, Flynn cosmetic and functional criteria, and time required to regain full elbow range of motion. None of the differences were found to be statistically significant Groups

Group 1

Group 2

p

Fracture healing (days)

44.1 (30–56)

46.3 (40–55)

<0.05

Full satisfaction

21/30 (70%)

6/8 (75%)

<0.05

Flynn cosmetic

21/30 (70%)

6/8 (75%)

<0.05

Flynn functional

21/30 (70%)

6/8 (75%)

<0.05

Complete range of motion (days)

57.5 (40–70)

55.5 (50–65)

<0.05

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Table 4. Spearman’s correlation analysis of relationship between variables. Numbers are r-values and negative numbers show counter correlation Variable

Flynn criteria

Time for union

Time for ROM

Gartland type

-1

-4.65

-5.29

Not significant

Time for union

-4.65

Not applicable

0.86

Not significant

Splinting time

Not significant

0.38

0.39

Not significant

Age

Not significant

Not significant

Not significant

0.39

Satisfaction

ROM: Range of motion.

and 6 of 8 (75%) patients (and parents) in Group 2 were totally satisfied with the results; there was no statistically significant difference between groups (p<0.05). According to Flynn cosmetic and functional criteria, all the results were satisfactory; there were no fair or poor scores. As in the patient satisfaction assessment, 21 of 30 (70%) patients in Group 1, and 6 of 8 (75%) patients in Group 2 had excellent cosmetic and functional outcomes according to the ranking criteria. Differences in all these results were not statistically significant (p<0.05) (Table 3). Correlation between variables was evaluated using Spearman’s correlation analysis. Full satisfaction was negatively correlated with Flynn criteria (Flynn score of 1 is excellent, 2 is good), and negatively correlated with fracture union and length of time to full ROM. Time required to achieve full ROM was correlated with fracture union time and splinting time. Age was correlated with Gartland classification; older children had highest level of classification (type III) (Table 4).

DISCUSSION Supracondylar humerus fracture is the most common surgically treated fracture seen during childhood.[13] Treatments for displaced supracondylar humerus fracture are closed reduction and internal fixation or open reduction and internal fixation,[13] and numerous surgical techniques have been described in the literature.[13,14] Anatomical reduction and stable fixation with good cosmetic appearance and full ROM are the treatment goals.[7,9] Closed reduction and percutaneous pinning is the commonly accepted primary method of treatment.[13,14] Under some conditions, however, such as soft tissue entrapment, severely displaced fracture, very edematous elbow, open fracture, or neurovascular injury, open reduction may be required.[5–7,15,16] A lateral, medial, anterior, or posterior approach can be used for open reduction.[8,17] Most surgeons prefer medial or lateral approach,[5,18] but anterior approach is also a safe and simple method.[6,19,20] Though lateral approach is widely used, it has been stated that unsatisfactory reduction, and therefore objectionable clinical results, are of high probability in cases of exploration of only one cortex.[21] 486

There is a scarcity in the literature about posterior approach for pediatric supracondylar fracture surgery. There are a few reports describing posterior exposure; however, fracture sites were reached via lateral or medial paratricipital approach,[9,22] or through a tongue-shaped flap of the aponeurosis with division of the remaining muscle fibers.[10] In these approaches, the surgeon must find and protect the ulnar nerve, which prolongs operation time.[9,10,22] Additionally, risk of neuropraxia is higher with exploration of the nerve rather than keeping it safely in cubital tunnel, since ulnar nerve palsies after open reduction are usually a traction injury.[23] In Group 1 of the present study, the triceps was split on the midline, allowing direct access to the fracture site and easy reduction of fracture. Ulnar nerve exploration and protection were not required since pin insertion could be directly observed. Splitting the triceps muscle provides wide exposure; however, it has been stated that cutting the muscle prevents early rehabilitation and therefore extension loss is common.[24] The immobilization period is usually 2–4 weeks after all types of pediatric supracondylar surgeries. Mean immobilization period was about 32 days in present study groups, so authors suggest that splitting the triceps for several centimeters does not prevent routine rehabilitation. It may be true for adults, however, because of a wider approach for distal humerus fracture and probably a longer immobilization period. Traditionally, acute treatment of pediatric supracondylar fractures within 8 hours of the trauma is recommended in order to decrease risk of complications such as compartment syndrome, infection, and nerve injury, as well as to prevent increased swelling.[10,11,25] Poor results after open reduction and fixation are believed to be result of delay in treatment.[26] Present study operations were all performed on first day of admission, which likely contributed to low rate of complications (3 superficial pin infections). A weakness of this study may be imbalance in the number of group participants; however, statistical analysis was possible. Clinical outcomes and Flynn criteria were recorded by different residents on duty in the clinic, which could have affected the evaluation process. We found better results than expected with no poor outcomes. However, satisfaction was rated Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


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by the patient and the parents, and these results correlated with clinical outcomes and Flynn criteria. Another weakness of the study is that we did not perform any measurements on last x-rays. Humeral-ulnar angle,[23] Baumann’s angle, and lateral humerocapitellar angle[3] are among the measurements that can be used to evaluate accuracy of reduction and alignment of the extremity. Additionally, we did not record operation time, but since ulnar nerve was only explored in lateral approach, posterior approach may be more advantageous in terms of length of time required for surgery. In summary, like many authors, we believe that early closed reduction and percutaneous pinning is the optimal choice of treatment for pediatric supracondylar humerus fracture. When this method is not applicable, triceps-splitting posterior approach is a safe and comparable method to lateral approach with advantages of easier fracture reduction and shorter operation time. Conflict of interest: None declared.

REFERENCES 1. Pescatori E, Memeo A, Brivio A, Trapletti A, Camurri S, Pedretti L, et al. Supracondylar humerus fractures in children: a comparison of experiences. J Pediatr Orthop B 2012;21:505–13. 2. Ladenhauf HN, Schaffert M, Bauer J. The displaced supracondylar humerus fracture: indications for surgery and surgical options: a 2014 update. Curr Opin Pediatr 2014;26:64–9. 3. Kao HK, Yang WE, Li WC, Chang CH. Treatment of Gartland type III pediatric supracondylar humerus fractures with the Kapandji technique in the prone position. J Orthop Trauma 2014;28:354–9. 4. Gartland JJ. Management of supracondylar fractures of the humerus in children. Surg Gynecol Obstet 1959;109:145–54. 5. Ersan O, Gonen E, İlhan RD, Boysan E, Ates Y. Comparison of anterior and lateral approaches in the treatment of extension-type supracondylar humerus fractures in children. J Pediatr Orthop B 2012;21:121–6. 6. Cramer KE, Devito DP, Green NE. Comparison of closed reduction and percutaneous pinning versus open reduction and percutaneous pinning in displaced supracondylar fractures of the humerus in children. J Orthop Trauma 1992;6:407–12. 7. Basaran SH, Ercin E, Bilgili MG, Bayrak A, Cumen H, Avkan MC. A new joystick technique for unsuccessful closed reduction of supracondylar humeral fractures: minimum trauma. Eur J Orthop Surg Traumatol 2015;25:297–303. 8. Koudstaal MJ, De Ridder VA, De Lange S, Ulrich C. Pediatric supracondylar humerus fractures: the anterior approach. J Orthop Trauma 2002;16:409–12. 9. Bombaci H, Gereli A, Küçükyazici O, Görgeç M, Deniz G. The effect of surgical exposure on the clinic outcomes of supracondylar humerus fractures in children. Ulus Travma Acil Cerrahi Derg 2007;13:49-54. 10. Lal GM, Bhan S. Delayed open reduction for supracondylar fractures of

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the humerus. Int Orthop 1991;15:189–91. 11. Gürkan V, Orhun H, Akça O, Ercan T, Ozel S. Treatment of pediatric displaced supracondylar humerus fractures by fixation with two cross Kwires following reduction achieved after cutting the triceps muscle in a reverse V-shape]. Acta Orthop Traumatol Turc 2008;42:154–60. 12. Flynn JC, Matthews JG, Benoit RL. Blind pinning of displaced supracondylar fractures of the humerus in children. Sixteen years’ experience with long-term follow-up. J Bone Joint Surg Am 1974;56:263–72. 13. Omid R, Choi PD, Skaggs DL. Supracondylar humeral fractures in children. J Bone Joint Surg Am 2008;90:1121–32. 14. Ay S, Akinci M, Kamiloglu S, Ercetin O. Open reduction of displaced pediatric supracondylar humeral fractures through the anterior cubital approach. J Pediatr Orthop 2005;25:149–53. 15. Kazimoglu C, Cetin M, Sener M, Aguş H, Kalanderer O. Operative management of type III extension supracondylar fractures in children. Int Orthop 2009;33:1089–94. 16. Diri B, Tomak Y, Karaismailoğlu TN. The treatment of displaced supracondylar fractures of the humerus in children (an evaluation of three different treatment methods). Ulus Travma Acil Cerrahi Derg 2003;9:62– 9. 17. Aktekin CN, Toprak A, Ozturk AM, Altay M, Ozkurt B, Tabak AY. Open reduction via posterior triceps sparing approach in comparison with closed treatment of posteromedial displaced Gartland type III supracondylar humerus fractures. J Pediatr Orthop B 2008;17:171–8. 18. Reitman RD, Waters P, Millis M. Open reduction and internal fixation for supracondylar humerus fractures in children. J Pediatr Orthop 2001;21:157–61. 19. Danielsson L, Pettersson H. Open reduction and pin fixation of severely displaced supracondylar fractures of the humerus in children. Acta Orthop Scand 1980;51:249–55. 20. Gosens T, Bongers KJ. Neurovascular complications and functional outcome in displaced supracondylar fractures of the humerus in children. Injury 2003;34:267–73. 21. Weiland AJ, Meyer S, Tolo VT, Berg HL, Mueller J. Surgical treatment of displaced supracondylar fractures of the humerus in children. Analysis of fifty-two cases followed for five to fifteen years. J Bone Joint Surg Am 1978;60:657–61. 22. Young S, Fevang JM, Gullaksen G, Nilsen PT, Engesæter LB. Parent and Patient Satisfaction after Treatment for Supracondylar Humerus Fractures in 139 Children: No Difference between Skeletal Traction and Crossed Pin Fixation at Long-Term Followup. Adv Orthop 2012;2012:958487. 23. Ozkoc G, Gonc U, Kayaalp A, Teker K, Peker TT. Displaced supracondylar humeral fractures in children: open reduction vs. closed reduction and pinning. Arch Orthop Trauma Surg 2004;124:547-51. 24. Gruber MA, Hudson OC. Supracondylar fracture of the humerus ın childhood. End-result study of open reduction. J Bone Joint Surg Am 1964;46:1245–52. 25. Harris IE. Supracondylar fractures of the humerus in children. Orthopedics 1992;15:811–7. 26. Ababneh M, Shannak A, Agabi S, Hadidi S. The treatment of displaced supracondylar fractures of the humerus in children. A comparison of three methods. Int Orthop 1998;22:263–5.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Pediatrik suprakondiler humerus kırıklarının tedavisinde trisepsi kesen posterior ve lateral yaklaşımın karşılaştırılması Dr. Faik Türkmen,1 Dr. Serdar Toker,1,2 Dr. Kayhan Kesik,1 Dr. İsmail Hakkı Korucu,1 Dr. Mehmet Ali Acar3 1 2 3

Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Konya Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, El ve Üst Ekstremite Cerrahisi Bilim Dalı, Konya Selçuk Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Konya

AMAÇ: Suprakondiler humerus kırıkları çocukluk döneminin en sık dirsek kırığıdır. Kapalı redüksiyon ve perkütan çivileme altın standart tedavi olarak kabul edilir. Bununla beraber bazen açık redüksiyon gerekebilir. Bu geriye dönük çalışmamızın amacı suprakondiler humerus kırıklarında triseps kasını kesen posterior ve lateral yaklaşımların klinik ve fonksiyonel sonuçlarını karşılaştırmaktır. GEREÇ VE YÖNTEM: Toplam 38 hasta posterior veya lateral insizyonla ameliyat edildi. Grup 1’de posterior insizyonlu 30 hasta, Grup 2’de lateral insizyonlu sekiz hasta mevcuttu. Kozmetik ve klinik sonuçları karşılaştırmak için Flynn kriterleri kullanıldı. Kırık kaynaması AP ve lateral grafilerle değerlendirildi. Hastalar ve ebeveynlerine dirseğini tam aktif olarak ne kadar sürede hareket ettirebildiği ve tedavi sürecinden tatmin durumları sorularak kayıt tutuldu. BULGULAR: Ortalama kaynama süresi Grup 1 ve Grup 2 için sırasıyla 44.1 gün ve 46.3 gün, tam veya tama yakın dirsek hareketlerine kavuşma süresi Grup 1 ve Grup 2 için sırasıyla atel çıkarımı sonrası 57.5 ve 55.7 gün olarak bulundu. Grup 1’deki 30 hastanın ve ebeveynin 21’i (%70), Grup 2’deki sekiz hastanın ve ebeveynin altısı (%75) sonuçtan tam olarak tatmin olduklarını ifade ettiler. Grup 1’deki 30 hastanın 21’i (%70), Grup 2’deki sekiz hastanın ve altısı (%75) her iki Flynn kriterlerine göre (kozmetik ve fonksiyonel) çok iyi grupta yer aldı. TARTIŞMA: Pediatrik suprakondiler humerus kırıklarının tedavisinde kapalı redüksiyon ve perkütan çivilemenin altın standart tedavi olduğuna inanıyoruz. Bu metodun uygulanamadığı olgularda trisepsi kesen posterior yaklaşımın daha kolay kırık redüksiyonu ve muhtemelen daha kısa ameliyat süresi gibi avantajlarından dolayı güvenli ve lateral yaklaşımla karşılaştırılabilir olduğunu düşünüyoruz. Anahtar sözcükler: Posterior yaklaşım; suprakondiler humerus kırığı; triseps. Ulus Travma Acil Cerrahi Derg 2016;22(5):483–488

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doi: 10.5505/tjtes.2016.74606

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ORİJİ N A L Ç A LI Ş M A

Yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesi RN, PhD. Berrin Pazar,1 RN, PhD. Emine İyigün,1 Dr. İsmail Şahin2 1

Gülhane Askeri Tıp Akademisi, Hemşirelik Yüksek Okulu, Cerrahi Hastalıklar Hemşireliği Bilim Dalı, Ankara

2

Gülhane Askeri Tıp Akademisi, Plastik ve Rekonstrüktif Cerrahi Anabilim Dalı (Emekli, Serbet Hekim), Ankara

ÖZET AMAÇ: Bu araştırmanın amacı yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesidir. GEREÇ VE YÖNTEM: Araştırma, bir üniversite hastanesinde Ocak 2014–Haziran 2015 tarihleri arasında tanımlayıcı olarak yapıldı. Araştırmaya 36 hasta (32 erkek, 4 kadın; ortalama yaş 26.69±9.63; dağılım 19-60 yıl) alındı. Verilerin toplanmasında hastaların tanıtıcı özelliklerini belirleyen form ve Pittsburgh Uyku Kalitesi İndeksi (PUKİ) kullanıldı. Araştırmadan elde edilen verilerin analizi için SSPS 22.0 paket programı kullanıldı, tüm analizlerde istatistiksel önemlilik için p<0.05 kabul edildi. BULGULAR: Hastaların %50’sinin yanık yarası evde alev yanığı nedenlidir. Yanığa bağlı hastaların %52.8’inde komplikasyon gelişmiştir. Hastaların PUKİ skor ortalaması 9.30±4.03’tür ve %86.5’inin uyku kalitesi kötüdür. Hastaların yoğun bakımda yatma, eğitim durumu, yanık alanı yüzdesi, yanık yaralanmasının üzerinden geçen zaman ve ilaç kullanma (antidepresan, antipsikotik) durumu ile Pittsburgh Uyku Kalitesi ortalamaları arasında istatistiksel olarak anlamlı bir ilişki bulunmuştur (p<0.05). SONUÇ: Araştırmaya katılan hastaların uyku kalitesinin kötü olduğu değerlendirilmiştir. Yanık yaralanması sonrasında yeterli uykunun, doğal savunma hücrelerinin işlevini, protein sentezini ve büyüme hormonu salınımını arttırarak yanık yaralarının iyileşmesini sağladığı bilinmektedir. Bu nedenle hastaların uyku kalitesi ve yaşadıkları uyku problemlerinin bilinmesinin, yanıklı hastaların hemşirelik bakımının gelişmesine katkı sağlayacağı düşünülmektedir. Anahtar sözcükler: Hemşirelik bakımı; uyku kalitesi; yanık yarası.

GİRİŞ Yanık yaralanması, birey üzerinde fiziksel ve psikolojik etkileri olan, uzun süreli tedavi ve hastaneye yatmayı gerektiren bir travmadır.[1] Yapılan çalışmalarda yanık hastalarının travma sonrasında karşılaştığı psikososyal sorunların, bireyin uyku ve dinlenme kalitesini olumsuz yönde etkilediği ve uyku bozukluklarının sık görüldüğü bildirilmiştir.[2,3] Bu dönemde görülen uyku bozukluğu; hastanede yatma, ortamın gürültülü olması, bunlara bağlı sirkadyen ritminde bozulma, yanığa bağlı hipermetabolizma, kaşıntı ve ağrı, eşlik eden anksiyete, depresyon gibi duygu

Sorumlu yazar: Dr. Berrin Pazar, GATA Hemşirelik Yüksek Okulu, Cerrahi Hastalıkları Hememşireliği Bilim Dalı, Etlik, Keçiören, 06018 Ankara. Tel: +90 312 - 304 39 36 E-posta: bpazar@gata.edu.tr Ulus Travma Acil Cerrahi Derg 2016;22(5):489–494 doi: 10.5505/tjtes.2016.70137 Telif hakkı 2016 TJTES

Ulus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5

durum değişiklikleri ile ilişkili olabilir.[2,4–6] Ayrıca hastanın ağrı kontrolü, yaşam bulgularının izlemi ve ilaç tedavisi için gece boyunca sık sık uyandırılması ve hastaların yanık yaralanması nedeniyle kâbuslar görmesi uyku kalitelerini etkilemektedir.[2,7] Uyku, organizmanın ve zihnin yenilendiği, onarıldığı, geliştiği bir dönem olup temel bir gereksinimdir.[8] Çalışmalar uykunun semptomlu sinir aktivasyonu ve metabolizma hızını azalttığını, lenfosit sayısını, doğal savunma hücrelerinin işlevini, protein sentezini ve büyüme hormonu salınımını artırdığını göstermektedir.[4,9] Uzun süreli uyku yoksunlukları yara iyileşme sürecini uzatmakta ve komplikasyonlara karşı yanık yarasının savunmasız hale gelmesine neden olmaktadır.[10] Uykuya ilişkin bu bilgilere rağmen sağlık profesyonelleri çoğunlukla hastaların tıbbi tanılarıyla ilgili şikâyetlerini ön planda tutmakta uyku ile ilgili rahatsızlıklarını ihmal etmektedir.[11] Yurtdışı çalışmalarda yanık hastalarının uyku problemlerinin incelendiği görülmektedir.[3–5,12,13] Ancak yurt içi yapılan araştırmalar incelendiğinde yanık hastalarının uyku kalitesinin uyku ölçeğiyle belirlendiği çalışmaya ihtiyaç olduğu tespit edilmiştir. Pittsburgh Uyku Kalitesi İndeksi (PUKİ) iyi ve kötü uykunun 489


Pazar ve ark. Yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesi

tanımlanmasına yarayan uyku kalitesinin niceliksel bir ölçümünü veren kendi içinde tutarlılığı olan ve tekrar edilebilen, güvenilir bir ölçektir.[14] Buysse ve ark. tarafından (1989) geçerlilik ve güvenirlik çalışması yapılmıştır. Ülkemizde ise geçerlilik ve güvenirlik çalışması Ağargün ve ark. tarafından (1996) yapılmıştır.[15] Toplam PUKİ puanının 5 ve üzerinde olması kötü uyku kalitesini göstermektedir. Çalışmamızda PUKİ’yi kullanarak yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesini amaçladık. Çalışmanın yanık hastalarının uyku kalitesini belirleyerek sağlık profesyonellerinin hastaların uyku kalitesine ilişkin farkındalığını artıracağı ve hastaların uykuya yönelik sorunlarının tanımlanmasında ve çözümlenmesinde yol gösterici olacağı düşünülmektedir.

GEREÇ VE YÖNTEM Araştırmanın Şekli, Evren ve Örneklemi

independent samples t-test (student t-testi), üçlü grup karşılaştırmalarında tek yönlü varyans analizi (One Way Anova) uygulanmıştır. Tüm analizlerde istatistiksel önemlilik için p<0.05 kabul edilmiştir.

BULGULAR Tablo 1’de hastaların tanıtıcı özellikleri verilmiştir. Tabloya Tablo 1. Hastaların tanıtıcı özellikleri (n=36) Tanıtıcı özellikler

n

%

Yaş (Ort.=26.69±9.63, aralık=19–60) 19–35

31 86.1

36–60

5 13.9

Cinsiyet Kadın

4 11.1

Bu araştırma kesitsel tanımlayıcı araştırma olarak planlanmıştır. Ocak 2014–Haziran 2015 tarihleri arasında bir eğitim ve araştırma hastanesi yanık merkezinde tedavi edilen ya da daha önce yanık yarası nedeniyle tedavi edilmiş olup belirtilen tarihler arasında tekrar tedavi nedeniyle yatan tüm hastalar araştırmanın evrenini oluşturmuştur. Belirtilen dönemde araştırmaya katılmayı kabul eden, Türkçe bilen, 18 yaş ve üzeri olan, yanık yaralanması üzerinden en az bir ay geçen ve yanık merkezinde tedavi edilen 36 hasta araştırmanın örneklemini oluşturmuştur.

Erkek

32 88.9

Bekar

27 75.0

Araştırmanın Uygulanması

8

Vücut kitle indeksi Zayıf

1 2.8

Normal kilolu

20

55.6

Hafif obez

10

27.8

Obez

4 11.1

1

Morbid obez

2.8

Medeni durum Evli

Araştırmaya başlamadan önce araştırmanın yapıldığı hastanenin etik kurulundan gerekli izinler alınmıştır (Etik Kurul Onay Nu: 1648-12 Aralık 2013/28). Yanık merkezinde tedavi olan ve örneklem ölçütlerine uyan hastalara, yanık yarasının oluşma tarihi üzerinden en az bir ay geçmesinden sonra anketler uygulanmıştır. Anketler yüz yüze görüşülerek doldurulmuş, bir anketin doldurulması 15 dakika sürmüştür. Anket uygulamasına başlamadan önce tüm hastalara araştırma hakkında bilgi verilerek yazılı onam belgesi alınmıştır.

Dul

22.2

1 2.8

Eğitim durumu İlköğretim

11 30.6

Lise

14 38.9

11

Üniversite

30.6

Mesleği İşçi

21 58.3

Özel sektör

10

27.8

Memur

4

11.1

Verilerin Toplanması

Ev hanımı

1

2.8

Veri toplamak amacıyla araştırmacı tarafından geliştirilen hastaların tanıtıcı özelliklerini belirleyen form ve PUKİ kullanılmıştır.

Evet

2 5.6

Hayır

34 94.4

Kronik hastalık durumu

Hasta tanılama formu; hastaların yaş, cinsiyet, vücut kitle indeksi (VKİ), mesleği, medeni durumu, eğitim durumu, kronik hastalık durumu, sigara, alkol, ilaç kullanım durumları, yoğun bakımda yatma, yanığın oluşma tarihi, yanığın oluşma sebebi, yanığın yüzdesi, yanığa bağlı gelişen komplikasyon durumu sorularını içermektedir.

Sigara kullanım durumu

Verilerin Değerlendirilmesi

İlaç kullanım durumu

Araştırmadan elde edilen verilerin analizi için SSPS 22.0 paket programında yüzde, frekans, aritmetik ortalama ve standart sapma değerleri hesaplanmıştır. İkili grup karşılaştırmalarında 490

Evet

15 41.7

Hayır

21 58.3

Alkol kullanım durumu Evet

2 5.6

Hayır

34 94.4

Evet

11 30.6

Hayır

25 69.4

Ulus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5


Pazar ve ark. Yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesi

Tablo 2. Hastaların yanık yaralanmasına ilişkin bulguları (n=36) Yanığa ilişkin bilgiler

n

%

Tablo 3. Pittsburgh Uyku Kalitesi İndeksi (PUKİ) ve alt boyutları (n=36) Ort.±SS

Yanığın oluşması üzerinden geçen zaman

1 ay–5 yıl

27

75

Öznel uyku kalitesi

1.63±0.68

10 ve üzeri

9

25

Uyku latensi

1.83±0.91

Uyku süresi

1.83±1.10

11.1

Alışılmış uyku etkinliği

0.91±1.02 1.33±0.63

Yanığın oluştuğu yer

Araç içi

4

İş yeri

14

38.9

Uyku bozukluğu

Ev

18

50.0

Uyku ilacı kullanımı

1.05±1.39

Gündüz işlev bozukluğu

1.44±0.96

Global PUKİ toplam puanı

9.30±4.03

Yanık sebebi

Kimyasal madde

2

5.6

Elektrik

5 13.9

Haşlanma

10 27.7

Alev

19 52.8

Yanık yüzdesi (Ort.=23.80±16.31, aralık=5–65) 5–20

23 63.9

21–65

13 36.1

Yanığa bağlı komplikasyon gelişme durumu Evet

19 52.8

Hayır

17 47.2

Ort.: Ortalama; SS: Standart sapma.

Tablo 4. Hastaların uyku kalitesi düzeyleri (n=36) Uyku kalite düzeyi

n

%

Uyku kalitesi iyi (0–4.99 puan alanlar)

5

13.5

Uyku kalitesi kötü (5 ve üzeri puan alanlar)

31

86.5

Toplam

36 100

Yoğun bakımda yatma durumu Evet

12 33.3

Hayır

24 66.7

göre hastaların yaş ortalamaları 26.69±9.63 ve 19–60 aralığında olup %11.1’i kadın, %88.9’u erkektir. Hastaların %55.6’sı normal kiloda, %75’i bekâr, %38.9’u lise mezunu, %58.3’ü işçi, %41.7’si sigara kullanmaktadır. Hastaların %5.6’sının kronik hastalığı bulunmaktadır. Kronik hastalığı olan hastalardan biri tip II diyabet, diğeri epilepsi hastasıdır (tabloda gösterilmemiştir). Yanık yaralanması sonrasında uyumaya yardımcı olması için ilaç kullanma oranı %30.6’dır. İlaç kullanan hastaların ikisi antidepresan, dokuzu antipsikotik kullanmaktadır (tabloda gösterilmemiştir). Tablo 2’de hastaların yanık yaralanmasına ilişkin bulguları verilmiştir. Tabloya göre hastaların %75’inin yanık yaralanmasının üzerinden bir ay ile beş yıl arası zaman geçmiştir. Yanık yaralanması yeni olan tüm hastaların yanık derecesi ikinci ve üçüncü derecedir (tabloda gösterilmemiştir). Yanık yaralanmasının %50’si evde, %38.9’u iş yerinde gerçekleşmiş olup %52.8’inin nedeni alev yaralanmalarıdır. Yanık alanı yüzdesi ortalaması 23.80±16.31 ve 5–65 aralığındadır. Yanığa bağlı hastaların %52.8’inde komplikasyon gelişmiştir. Gelişen komplikasyonlar bir hastada böbrek yetersizliği, iki hastada kontraktür, bir hastada emboli, bir hastada solunum sıkıntısı, bir hastada ödem, on bir hastada enfeksiyondur. Komplikasyonlara bağlı iki hastaya ampütasyon yapılmıştır (tabloda gösterilmemiştir). Ulus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5

Tablo 3’de PUKİ ve alt boyutları ortalamaları verilmiştir. Tablo’ya göre hastaların toplam PUKİ puanı 9.30±4.03’tür. Tablo 4’de hastaların uyku kalitesi düzeyleri verilmiştir. Tabloya göre hastaların %86.5’inin uyku kalitesi kötü, %13.5’inin uyku kalitesi iyidir. Tablo 5’de hastaların tanıtıcı özelliklerine göre uyku kalitesi indeksi puan ortalamalarının karşılaştırılması verilmiştir. Tabloya göre hastanın yoğun bakımda yatma, yanık alanı yüzdesi, yanık yaralanmasının üzerinden geçen zaman, ilaç kullanma durumu, eğitim durumu ile Pittsburgh Uyku Kalitesi ortalamaları arasında istatistiksel olarak anlamlı bir ilişki bulunmuştur (p<0.05). Ancak hastaların yaş, cinsiyet, kronik hastalık, yanığa bağlı komplikasyon gelişimi, sigara, alkol kullanımı, VKİ, medeni durum ve meslekleriyle Pittsburgh Uyku Kalitesi ortalamaları arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır (p>0.05).

TARTIŞMA Bu araştırmada yanık merkezinde tedavi edilen hastaların uyku kalitesi incelenmiştir. Araştırmamızdaki hastaların %86.5’inin uyku kalitesinin kötü olduğu saptanmıştır. Boeve (2002) ve Masoodi’nin (2013) yanık yaralanması sonrası hastaların uyku problemlerini değerlendirdikleri çalışmalarında hastaların sırasıyla %73, %61.2 oranında uyku problemi yaşadıklarını tespit etmişlerdir.[4,16] Karateke (2010) yanıklı hastalarda ağrı, anksiyete ve depresyon ilişkisini incelediği çalışmasında ise yanık öncesi uyku sorunu yaşamayan hastaların büyük çoğunluğu491


Pazar ve ark. Yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesi

Tablo 5. Hastaların tanıtıcı özelliklerine göre uyku kalitesi indeksi puan ortalamalarının karşılaştırılması (n=36) Özellikler

Uyku kalitesi ortalaması n

Ort.±SS

test p

Yaş 19–35

31 9.03±4.07 *t=-1.01 0.31

36–60

5 11.00±3.67

Cinsiyet

Kadın

4

10.25±4.64

Erkek

32

9.18±4.01

t=0.49 0.62

*

Kronik hastalık durumu Evet

2 8.50±4.94 *t=-0.28 0.77

Hayır

34 9.35±4.05

Komplikasyon gelişme durumu Evet

19 10.00±4.01 *t=1.09 0.28

Hayır

17 8.52±4.03

Yoğun bakımda yatma

Tablo 5. Hastaların tanıtıcı özelliklerine göre uyku kalitesi indeksi puan ortalamalarının karşılaştırılması (n=36) (devamı) Özellikler

Uyku kalitesi ortalaması n

Ort.±SS

test p

Medeni durum Bekar

27 8.77±4.20 **=1.22 0.30

8

Evli

Dul

11.25±3.19

1 8.00±0.00

Eğitim durumu

İlköğretim

11

7.81±3.12

Lise

14

11.71±4.04

Üniversite

11

7.72±3.55

=5.02 0.01

**

Mesleği Memur

4 10.00±4.69 **=1.25 0.30

İşçi

21 8.71±4.26

Ev hanımı

1

4.00±0.00

Özel sektör

10

10.80±2.97

Ort.: Ortalama; SS: Standart sapma; *Student t-testi; **One Way ANNOVA.

durumu Evet

12 11.50±3.75 *t=2.47

24

Hayır

8.20±3.77

0.01

Sigara kullanımı Evet

15 10.00±4.56 *t=0.87 0.39

Hayır

21 8.80±3.64

Alkol kullanımı Evet

2 10.50±3.53 *t=0.42 0.67

Hayır

34 9.23±4.09

İlaç kullanımı Evet

11 11.90±3.33 *t=2.81 0.00

Hayır

25 8.16±3.82

Yanığın oluşması üzerinden geçen zaman

0–5 yıl

27

10.07±3.78

10 ve üzeri

9

7.00±4.09

t=2.71 0.04

*

Yanık yüzdesi 5–20

23 8.26±4.19 *t=2.17 0.03

21–65

13 11.15±3.07

Vücut kitle indeksi Zayıf

1 6.00±0.00

Normal kilolu

20

8.90±4.27

Hafif obez

10

9.00±3.65

Obez

4 11.25±2.98

1

492

Morbid obez

16.00±0.00

=1.17 0.34

**

nun (%64) yanık sonrası hastanede yatma sürecinde uyku sorunu yaşadığını belirtmiştir.[17] Yanık hastalarında debritman, pansuman gibi ağrılı işlemlerin, cerrahi girişimlerin, travmatik yaralanma ile ilişkili önemli kayıplar sonucu yaşanılan stresin, hastanede yatarak tedavi ediliyor olmanın uyku bozukluklarına neden olabildiği düşünülmektedir. Bu sonuçlar doğrultusunda, özellikle hastanede yatarak tedavi gören yanık hastalarının uyku kalitelerinin iyileştirilmesi için uyku hijyeninin sağlanması, tedavi girişimlerinin uyku saatinde yapılmaması, gündüz uykusunun kısıtlanması önerilmektedir. Araştırmamızda hastaların %50’sinde yanık yaralanmasının evde gerçekleştiği tespit edilmiştir. Gözalan’ın (2007) yanık kliniğine yatan hastaların tanımlayıcı özelliklerini belirlemek için yaptığı çalışmasında benzer şekilde hastaların %67.6’sının, Masoodi’nin (2013) yanık yaralanması sonrasında uyku değişikliklerini değerlendirdiği çalışmasında da hastaların %83’ünün yanık yaralanmasının evde gerçekleşmiş olduğu saptanmıştır.[16,18] Bu açıdan bakıldığında yanık yaralanması oluşmadan önce toplumun yanık yaralanmasına ilişkin farkındalığının artırılmasının ve yanık yaralanmasının önlenmesine ilişkin eğitim programlarının düzenlenmesinin önemli olduğu değerlendirilmektedir. Araştırmamızda yanık merkezi yoğun bakımında yatan hastaların yanık merkezi kliniğinde yatan hastalara göre uyku kalitelerinin daha kötü olduğu tespit edilmiştir. Yangzom (2015) yanıklı çocuk hastalardaki uyku bozukluklarına Diphenhydramine’in etkisini incelediği çalışmasında yoğun bakımda yatan yanıklı hastalarda uyku problemlerinin daha fazla görüldüğünü belirtUlus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5


Pazar ve ark. Yanık hastasında sub akut ve kronik dönemde uyku kalitesinin belirlenmesi

miştir.[13] Literatürde yoğun bakım ortamında hastaların uzun süre düşük seviyede yapay ışığa maruz kalması, diğer hastaların ve çalışanların gürültüsü, monitör alarmlarının sık çalması, hastaların yaşadıkları anksiyete, depresyon gibi duygu durum değişiklikleri, ağrı yönetimi ve bakım için yapılan girişimler nedeniyle sirkadyen ritimde bozulma ve buna bağlı uykuya dalma sürecinde uzama, uyku sürecinin bölünmesi ve sabah erken uyanma gibi hastaların uyku kalitesini düşüren bulgular görüldüğü bildirilmiştir.[19,20] Sağlık profesyonellerinin bu bulguları dikkate alarak uykuyu etkileyen faktörleri kontrol altına almasının hastaların uyku kalitesini artırmada etkili olacağı düşünülmektedir. Araştırmamızda eğitim düzeyi yükseldikçe hastaların uyku kalitelerinin düştüğü tespit edilmiştir. Yanıklı hastaların eğitim durumları ve depresyon oranlarını inceleyen bir çalışmada, lise mezunu düzeyindeki bireylerde diğer eğitim seviyelerindeki bireylere göre daha yüksek oranda (%37.7–43) depresyon görüldüğüne dikkat çekilmiştir.[12] Depresyondaki hastaların büyük bir çoğunluğunun uyku kalitesi bozukluğundan, uykuya dalma güçlüğünden, gece sık ve sabah erken uyanmaktan yakındıkları bildirilmiştir.[21] Dolayısıyla eğitim düzeyi yüksek hastalarda depresyon ve buna bağlı uyku problemi görülme sıklığının daha fazla olduğu söylenebilir. Bu sonuca göre hastaların eğitim düzeyine göre değişen eğitim ihtiyaçlarının belirlenerek bilgilendirilmesi ve rehabilitasyon programlarının düzenlenmesi önerilmektedir. Araştırmamızda yanık alanı yüzdesi 20 ve üzeri olan hastaların uyku kalitelerinin yanık alanı yüzdesi 20’nin altında olan hastalardan daha kötü olduğu saptanmıştır. Masoodi’nin (2013) yanık yaralanması sonrasında uyku değişikliklerini değerlendirdiği çalışmasında hastaların yanık alanı yüzdesi arttıkça uyku kalitesinin düştüğü tespit edilmiştir.[16] Yanık alanı yüzdesinin yüksek olması nedeniyle hastaların daha fazla ağrı deneyimledikleri düşünülmektedir. Yapılan çalışmalarda yanık hastalarında ağrının uyku kalitesini düşürdüğünü bildirilmiştir. [6,7,17] Ayrıca hastaların yanık alanı yüzdesi arttıkça yara iyileşmesinin gerçekleşmesi için hastanede geçirdikleri süre de uzamaktadır.[16] Bu süreçte hastaların, hastane ortamını farklı ve yabancı bir ortam olarak değerlendirmesi, odalarının havasız olması, tedavi için uyandırılması, sabah erken saatte kahvaltı verilmesi, konuşmaların yüksek sesle yapılıyor olması ve yanık yara yerlerinin ağrımasına bağlı olarak uyku alışkanlıklarında değişiklikler yaşadıkları değerlendirilmiştir.[2,7] Hastaların uyku kalitelerinin artırılmasında hastanede tedavi oldukları süre içinde uyku alışkanlıklarını değiştiren bu uyarıların sağlık profesyonelleri tarafından kontrol altına alınması önem kazanmaktadır. Araştırmamızda yanık yaralanmasının üzerinden bir ay–beş yıl zaman geçen hastaların uyku kalitesinin, yaralanma üzerinden 10 ve üzeri yıl zaman geçen hastalara göre daha kötü olduğu saptanmıştır. Smith (2008) majör yanık yaralanması sonrası hastanede yatan hastalarda uyku problemlerine ağrının etkisini incelediği çalışmasında yanık yaralanmasının yeni oluştuğu Ulus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5

hastaların ağrı yaşaması nedeniyle gece uyuyamadıklarını saptamıştır.[6] Ayrıca yanık yaralanmasının yeni oluştuğu hastaların yanık yaralanmasına ait yaşadıkları olayların taze olması ve sık sık olay anını hafızalarında canlandırmaları hastaları strese sokmakta ve bu durum da uyku kalitesini düşürmektedir.[22] Yanık yaralanmasının yeni oluştuğu hastalarda tedavi süreci, bu süreç içinde hastaların rol ve fonksiyonlarındaki değişiklikler, taburculuk sonrası yaşanılacakların belirsizliği gibi durumlar da hastalarda anksiyete, stres yaratmakta ve bunların sonucunda uyku problemleri ortaya çıkabilmektedir.[7] Bu açıdan bakıldığında yanık yaralanması sonrasında hastaların uyku problemlerinin nedenlerinin tespit edilerek uyku problemlerinin genel sağlığa olan olumsuz etkilerinin belirlenmesi ve tedavi edilmesi için rehabilitasyon programlarından yararlanmasının sağlanmasının hastaların uyku kalitelerini arttıracağı düşünülmektedir. Araştırmamızda uyku kalitesi kötü olan yanıklı hastaların uyku problemlerini önlemeye yönelik hekim istemine uygun olarak antipsikotik ve antidepresan kullandıkları tespit edilmiştir. Yangzom (2015) yanık hastalarında kaşıntı, anksiyete, depresyon ve ağrının uyku problemlerine yol açtığını ve sebebe yönelik tedavi için antihistaminik, antidepresan, antianksiyolitik, analjeziklerin kullanımının uyku problemlerinin azaltılmasında etkili olduğunu belirtmiştir.[13] Cen’in (2015) yanık hastaları için hazırlamış oldukları guideline’da hastaların uyku bozukluklarını azaltmada farmakolojik ajan kullanılması tavsiye edilmiştir.[23] Jaffe’nin (2004) derlemesinde yanık hastalarındaki uyku problemlerini azaltmak için antidepresan kullanımı önerilmiştir.[2] Blakeney’in (2008) ve Raymond’un (2004) çalışmalarında uyku bozukluklarına sebep olan anksiyetenin azaltılmasında farmokolojik müdahalelerde bulunulması önerilmiştir.[5,24] Antipsikotik, antianksiyolotik ve antidepresan gibi farmakolojik ajanlar yanık gibi akut stres durumunda uykuya başlama, uykuyu devam ettirme veya uyanıklığı takiben tekrar uykuya dönme problemleri için kullanılmaktadır. Kliniğimizde uyku problemi yaşayan hastalar için psikiyatri kliniğinden konsültasyon alınarak hastaların farmakolojik ajanlar kullanması sağlanmaktadır.

Sonuç Uyku vücudun en temel ihtiyaçlarından biridir, uyku sorunları bireylerin öz-bakım gücünü azaltmaktadır. Yanık yaralanması sonrasında yeterli uyku, doğal savunma hücrelerinin işlevini, protein sentezini ve büyüme hormonu salınımını artırarak yanık yaralarının iyileşmesini sağlamaktadır. Yanıklı hastalarda çoğu zaman hastaların fiziksel rahatsızlıklarına odaklanılmakta ve uyku problemleri ihmal edilmektedir. Bu nedenle yanık hastalarının uyku kalitesinin belirlenmesi, sağlık profesyonellerinin hastaların uyku kalitesine ilişkin farkındalığını arttırmakta, hasta bakımına uyku problemlerinin dâhil edilmesi hastaların uykuya yönelik sorunlarının anlaşılmasında, çözümlenmesinde ve hastaların konforunu arttırmada yardımcı olmaktadır. Çıkar örtüşmesi: Çıkar örtüşmesi bulunmadığı belirtilmiştir. 493


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KAYNAKLAR 1. Alvi T, Assad F, Aurangzeb, Malik MA. Anxiety and depression in burn patients. J Ayub Med Coll Abbottabad 2009;21:137–41. 2. Jaffe SE, Patterson DR. Treating sleep problems in patients with burn injuries: practical considerations. J Burn Care Rehabil 2004;25:294–305. 3. Park SY, Choi KA, Jang YC, Oh SJ. The risk factors of psychosocial problems for burn patients. Burns 2008;34:24–31. 4. Boeve SA, Aaron LA, Martin-Herz SP, Peterson A, Cain V, Heimbach DM, et al. Sleep disturbance after burn injury. J Burn Care Rehabil 2002;23:32–8. 5. Raymond I, Ancoli-Israel S, Choinière M. Sleep disturbances, pain and analgesia in adults hospitalized for burn injuries. Sleep Med 2004;5:551– 9. 6. Smith MT, Klick B, Kozachik S, Edwards RE, Holavanahalli R, Wiechman S, et al. Sleep onset insomnia symptoms during hospitalization for major burn injury predict chronic pain. Pain 2008;138:497–506. 7. Hofland H, Faber A, Loey N. Sleep disturbances in adults with burns: Course and risk factors. Burns 2007;33;37–8. 8. Kamphuis J, Meerlo P, Koolhaas JM, Lancel M. Poor sleep as a potential causal factor in aggression and violence. Sleep Med 2012;13:327,34. 9. Palma BD, Tiba PA, Machado RB, Tufik S, Suchecki D. Immune outcomes of sleep disorders: the hypothalamic-pituitary-adrenal axis as a modulatory factor. [Article in Portuguese] Rev Bras Psiquiatr 2007;29 Suppl 1:S33–8. [Abstract] 10. Zaros MC, Ceolim MF. Sleep/wake cycle of women submitted to elective gynecological surgery with a one-day hospital stay. Rev Lat Am Enfermagem 2008;16:838–43. 11. Sateia MJ. Sleep in patients with cancer and HIV/AIDS. In: Lee-Chiong TL, Sateia MJ, Carskadon MA, editors. Sleep medicine. Philadelphia: Hanley and Belfus; 2002. p. 489–95. 12. Thombs BD, Haines JM, Bresnick MG, Magyar-Russell G, Fauerbach JA, Spence RJ. Depression in burn reconstruction patients: symptom prevalence and association with body image dissatisfaction and physical

function. Gen Hosp Psychiatry 2007;29:14–20. 13. Yangzom N, Gottschlich MM, Ossege J, Wangmo T, Kagan RJ. The effect of diphenhydramine on sleep in pediatric burn patients: a secondary analysis. J Burn Care Res 2015;36:266–71. 14. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213. 15. Ağargün MY, Kara H, Anlar O. The Validity and Reliability of the Pittsburgh Sleep Quality Index. Türk Psikiyatri Dergisi 1996;7:107–15 16. Masoodi Z, Ahmad I, Khurram F, Haq A. Changes in sleep architecture after burn injury: ‘Waking up’ to this unaddressed aspect of postburn rehabilitation in the developing world. Can J Plast Surg 2013;21:234–8. 17. Karateke Y. Yanıklı hastalarda ağrı, anksiyete ve depresyon ilişkisinin incelenmesi. İstanbul Üniversitesi, Sağlık Bilimleri Enstitüsü. (basılmamış yüksek lisans tezi). İstanbul: 2010. 18. Gözalan A. Sağlık Bakanlığı Ankara Numune Eğitim ve Araştırma Hastanesi Yanık kliniği’nde yatan hastaların tanımlayıcı özellikleri ve sonucu etkileyen faktörler: retrospektif kohort çalışması. Hacettepe Üniversitesi. Sağlık Bilimleri Enstitüsü. (basılmamış yüksek lisans tezi). Ankara: 2007. 19. Friese RS, Diaz-Arrastia R, McBride D, Frankel H, Gentilello LM. Quantity and quality of sleep in the surgical intensive care unit: are our patients sleeping? J Trauma 2007;63:1210–4. 20. Bihari S, Doug McEvoy R, Matheson E, Kim S, Woodman RJ, Bersten AD. Factors affecting sleep quality of patients in intensive care unit. J Clin Sleep Med 2012;8:301–7. 21. Çalıyurt O, Güdücü F. Depresyonda uyku yoksunluğu tedavisi uygulamaları. Klinik Psikiyatri 2004;7:120–6. 22. Patterson DR, Ptacek JT, Cromes F, Fauerbach JA, Engrav L. The 2000 Clinical Research Award. Describing and predicting distress and satisfaction with life for burn survivors. J Burn Care Rehabil 2000;21:490–8. 23. Cen Y, Chai J, Chen H, Chen J, Guo G, Han C, et al. Guidelines for burn rehabilitation in China. Burns & Trauma 2015;3:2–10. 24. Blakeney PE, Rosenberg L, Rosenberg M, Faber AW. Psychosocial care of persons with severe burns. Burns 2008;34:433–40.

ORIGINAL ARTICLE - ABSTRACT OLGU SUNUMU

Determination of subacute and chronic period sleep quality in burn patients Berrin Pazar, RN, PhD.,1 Emine İyigün, RN, PhD.,1 İsmail Şahin, M.D.2 1 2

Gülhane Military Medical Academy, School of Nursing, Surgical Nursing Department, Ankara-Turkey Gülhane Military Medical Academy, Department of Plastic and Reconstructive Surgery (Retired member), Ankara-Turkey

BACKGROUND: The aim of this study was to determine the sleep quality of patients treated at burn center. METHODS: The present study is descriptive research conducted between January 2014 and July 2015 at a university hospital. The study included 36 patients (32 male, 4 female; mean age 26.69±9.63; range 19 to 60 years). Patient information form and Pittsburgh Sleep Quality Index (PSQI) were used to collect data. SPSS software (version 22.0; SPSS Inc., Chicago, IL, USA) was used for the analysis of the data, and statistical significance was regarded as p<0.05 in all analyses. RESULTS: Burn injuries of 50% of the patients were due to flash burn that occurred in the house. Complications developed in 52.8% of the patients. PSQI score average of the patients was 9.30±4.03 and 86.5% of them suffer from poor sleep quality. It was found that there was a statistically significant correlation (p<0.05) between Pittsburgh Sleep Quality averages and patient being in the intensive care unit (ICU), education level, percentage of area burned, length of time that had passed since the burn, and medication (antidepressant or antipsychotic). DISCUSSION: The sleep quality of patients in the study was found to be of poor degree. It is known that after burn injury, sufficient sleep enhances the function of natural defense cells, protein synthesis, and release of growth hormones, thereby healing the burn injuries. Information about patient sleep quality and sleep problems can lead to the development of nursing care for patients suffering from burns. Keywords: Burn injury; nursing care; sleep quality. Ulus Travma Acil Cerrahi Derg 2016;22(5):489–494

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Early post-traumatic splenic arteriovenous fistula in the pancreatic arcade: Diagnosis by volume-rendered 3D reconstruction images Junya Tsurukiri, M.D.,1 Hidefumi Sano, M.D.,1 Hoshiai Akira, M.D.,1 Naoyuki Kaneko, M.D.2 1

Department of Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center, Tokyo-Japan

2

Department of Emergency Medicine, Fukaya Red Cross Hospital, Saitama-Japan

ABSTRACT Arteriovenous fistula (AVF) of splenic vessels is rare. It is most commonly caused by spontaneous rupture of an extant splenic artery aneurysm into an adjacent vein, or by traumatic or iatrogenic pseudoaneurysm. Blunt abdominal trauma can sometimes lead to vascular damage to spleen, resulting in AVF formation. Presently described is case of an elderly patient with high-grade splenic injury. Early post-traumatic AVF was detected by volume-rendered 3D reconstruction using fused arterial and venous phase computed tomography (CT) images. Keywords: Anastomosis; injury; reconstruction; shock; ultrasonography.

INTRODUCTION Splenic arteriovenous fistula (AVF) is usually seen as a complication of splenic aneurysm and is not common. Blunt abdominal trauma can sometimes lead to vascular damage to spleen, resulting in AVF formation. Described in the present report is case of an elderly patient with multiple traumas in whom early post-traumatic splenic AVF was detected using computed tomography (CT) angiography.

CASE REPORT Written informed consent was obtained from the patient with regard to this report. A 65-year-old woman with history of malignant lymphoma was admitted to emergency center with hemorrhagic shock resulting from a traffic accident. Patient was hemodynamically unstable and immediately received initial trauma resuscitation based on Advanced Address for correspondence: Junya Tsurukiri, M.D. 1163 Tatemachi Hachioji Tokyo, Japan Tel: +81-4256655611 E-mail: junya99@tokyo-med.ac.jp Qucik Response Code

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Trauma Life Support (ATLS) guidelines.[1] Focused assessment with sonography for trauma revealed fluid collection around spleen, and X-ray revealed unstable pelvic fractures (Fig. 1a). Values for hemoglobin, hematocrit, platelets, and prothrombin time (PT)-international normalized ratio (INR) were 8.1 g/dL (normal range: 11.0–17.0 g/dL), 25.3% (normal range: 34.0%–49.0%), 18.9×104/μL (normal range: 14–34×104/μL) and 1.56, respectively. Initial enhanced CT of abdomen revealed laceration of spleen, classified as CT grade III according to the American Association for the Surgery of Trauma (AAST) CT scale, and fluid collection (Fig. 1b).[2] However, extravasation of contrast medium (CM) was undetectable. Volume-rendered 3D reconstruction using fused arterial and venous phase CT images revealed aneurysm and AVF of an arterial branch arising from lower splenic lobar artery. This branch was evident at ventral side of splenic vein and along edge of the tail of the pancreas on 3D CT (Fig. 2). Pelvic enhanced CT revealed CM extravasations. Successful arterial embolization (AE) of pelvic arteries was performed. Angiography of splenic artery revealed aneurysm and early filling of splenic vein, consistent with AVF detected by 3D CT (Fig. 3a). Although AE of splenic artery was successful, inferior pancreatic artery (IPA) connected to dorsal pancreatic artery (DPA) flowed into aneurysm and AVF (Fig. 3b). After AE of IPA, greater pancreatic artery (GPA) was anastomosed to pancreatic arcade that flowed into the fistula (Fig. 3c). Absence of flow via anastomoses into fistula was confirmed, indicating that AE was successful (Fig. 3d). Patient was discharged from 495


Tsurukiri et al. Early post-traumatic splenic AVF

(a)

(b)

(c)

Figure 1. (a) Pelvic X-ray and CT revealed unstable fractures. (b) Initial enhanced CT of abdomen (arterial and venous phase). (c) Enhanced CT of abdomen 3 months after the accident (arterial and venous phase).

intensive care unit (ICU) 60 days after admission and was transferred to another hospital 4 months after the accident. During hospitalization, no signs of acute portal hypertension or mesenteric ischemia such as esophageal varices or ascites were present in CT images or clinical symptoms (Fig. 1c).

DISCUSSION AVF of splenic vessels is rare, and it is most commonly caused by spontaneous rupture into an adjacent vein of an extant splenic artery aneurysm, or traumatic or iatrogenic pseudoaneurysm.[3] The former occur more frequently in Ehlers– Danlos or Osler–Weber–Rendu syndromes. One report describes spontaneous development and rupture of splenic AVF in a patient with lymphoma.[4]

Nonoperative management (NOM) is a large part of the present strategy for splenic injury. AVF is usually a delayed posttraumatic splenic complication and should be taken into consideration with NOM of splenic injury. An established splenic AVF may be extrasplenic and present as a pulsatile mass, with continuous bruit and thrill, abdominal pain, or diarrhea due to congestion of mesenteric veins. Thus, an early post-traumatic splenic AVF that can cause intra-abdominal hemorrhage, as described in the present report, is considerably rare. Splenic AVF is diagnosed based on early portal phase findings of arteriography. However, a recent report has suggested that CT angiography is an effective noninvasive method for detection of splenic AVF.[5] Although volume-rendered 3D reconstruction of

(a)

(b)

(c)

(d)

Figure 2. Volume-rendered 3D reconstruction using fused arterial and venous phase CT images showed splenic aneurysm and AVF (arrow) Splenic vein (arrow head).

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Figure 3. (a) Angiography of splenic artery revealed aneurysm and early filling of splenic vein, consistent with AVF. (b) Inferior pancreatic artery connecting to DPA flowed into aneurysm and AVF. (c) Greater pancreatic artery was anastomosed to pancreatic arcade that flowed into the fistula. (d) The absence of flow via anastomoses into the fistula.

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arterial and venous phase CT scans is useful for such detection, this anatomical site is supplied by a complicated, anastomosing network that originates from splenic artery or DPA. Thus, both 3D CT and angiography are essential to define complex arterial supply to early post-traumatic splenic complications such as AVF so that treatment strategies can be optimized. Treatment of splenic AVF is indicated to avoid portal hypertension, high-output cardiac failure, and other related complications. Therefore, transcatheter arterial embolization is a safe and effective treatment that is an alternative to splenectomy.

REFERENCES

Acknowledgments

4. van der Meer P, Cossi A, Tsao JI. Splenic arteriovenous fistula in a patient with lymphoma. AJR Am J Roentgenol 1998;171:1377–9.

The authors would like to thank Enago (www.enago.jp) for the English language review. Conflict of interest: None declared.

1. American College of Surgeons Committee on Trauma. Advanced trauma life support (ATLS) for doctors, 7th ed., Chicago: American College of Surgeons; 2004. 2. Moore EE, Cogbill TH, Jurkovich GJ, Shackford SR, Malangoni MA, Champion HR. Organ injury scaling: spleen and liver (1994 revision). J Trauma 1995;38:323–4. 3. Maloo MK, Burrows PE, Shamberger RC. Traumatic splenic arteriovenous fistula: splenic conservation by embolization. J Trauma 1999;47:173–5.

5. Oguz B, Cil B, Ekinci S, Karnak I, Akata D, Haliloglu M. Posttraumatic splenic pseudoaneurysm and arteriovenous fistula: diagnosis by computed tomography angiography and treatment by transcatheter embolization. J Pediatr Surg 2005;40:43–6.

OLGU SUNUMU - ÖZET

Pankreasta erken evrede oluşan posttravmatik splenik arteriyovenöz fistül: Üç boyutlu volüm rekonstrüksiyon görüntüleriyle tanı Dr. Junya Tsurukiri,1 Dr. Hidefumi Sano,1 Dr. Hoshiai Akira,1 Dr. Naoyuki Kaneko2 1 2

Tokyo Tıp Üniversitesi Hachioji Tıp Merkezi, Acil Tıp ve Yoğun Bakım Bölümü, Tokyo-Japonya Fukaya Kızıl Haç Hastanesi, Acil Tıp Bölümü, Saitama-Japonya

Splenik damarların arteriyovenöz fistülü (AVF) nadirdir. En çok bir komşu vene mevcut bir splenik arter anevrizmasının spontan rüptürü, travma sonucu veya iyatrojenik psödoanevrizma nedeniyle meydana gelmektedir. Künt abdominal travma bazen dalakta vasküler hasara yol açabilmekte sonuçta AVF oluşmaktadır. Burada çok şiddetli splenik travmaya maruz kalmış yaşlı bir hasta tanımlanmıştır. Arteryel ve venöz fazlı bilgisayarlı tomografik (BT) görüntüler kullanılarak gerçekleştirilen üç boyutlu volüm rekonstrüksiyonu posttravmatik AVF erken dönemde tanımlanmıştır. Anahtar sözcükler: Anastomoz; rekonstrüksiyon; şok; travma; ultrasonografi. Ulus Travma Acil Cerrahi Derg 2016;22(5):495–497

doi: 10.5505/tjtes.2015.91962

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A rare disease mimics postoperative bile leakage: Invasive aspergillosis Fatih Mehmet Yazar, M.D.,1 Aykut Urfalıoğlu, M.D.,2 Ömer Faruk Boran, M.D.,2 Hamide Sayar, M.D.,3 Burhan Hakan Kanat, M.D.,4 Arif Emre, M.D.,1 Emrah Cengiz, M.D.,1 Ertan Bülbüloğlu, M.D.1 1

Department of General Surgery, Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

2

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

3

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

4

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

ABSTRACT Aspergillus fungi can cause serious infections, including intra-abdominal infection, particularly in patients with compromised immune system. Described in the present report is case of 46-year-old female patient who had undergone laparoscopic cholecystectomy (LC) at another healthcare facility. In early postoperative period, she had increasing complaints of swelling, nausea, and vomiting. On postoperative 19th day, she was referred to our clinic with diagnosis of acute abdomen. Surgery was performed with suspected possibility of bile leakage. However, pathological examination of soft, yellow-green mass found in subhepatic space determined it was fungus ball caused by fungi of the genus Aspergillus. Patient was diagnosed postoperative intra-abdominal aspergillosis (IAA). Key words: Invasive aspergillosis; laparoscopic cholecystectomy; postoperative bile leakage.

INTRODUCTION Aspergilli are hyphal fungi that are widely distributed in nature; their natural habitat is soil and decaying plant material. Having rich enzyme systems, they can decompose and use almost all types of organic material, and they can grow even at very low moisture levels compared to other microorganisms.[1] They do not need humans as a host to complete their life cycle, but under appropriate conditions they can become pathogenic in humans. They are a type of fungi present with high density in the air, and they can be carried anywhere by means of conidia that are dispersed in the atmosphere. They Address for correspondence: Fatih Mehmet Yazar, M.D. Sütçü İmam Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Kahramanmaraş, Turkey Tel: +90 344 - 280 34 34 E-mail: fmyazar@hotmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):498–501 doi: 10.5505/tjtes.2015.38932 Copyright 2016 TJTES

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often cause respiratory tract infections in humans; rarely, gastrointestinal tract, solitary abdominal organs, and lymph nodes may also be attacked. Although distribution may occur easily through blood, especially in immunosuppressive patients, particularly after construction or renovation work in hospitals, contamination of surgical instruments may cause deep abdominal surgical infections.[2] Described in the present report is case of intra-abdominal aspergillosis (IAA) in patient who underwent laparoscopic cholecystectomy (LC) at another medical center and was subsequently admitted to our hospital in postoperative period with suspicion of leak.

CASE REPORT LC for symptomatic cholelithiasis was performed on 46-yearold female patient at another medical facility. After epicrisis and talking with surgeon who performed the operation, patient was assessed for right upper quadrant (RUQ) pain. Preoperative routine laboratory values had been normal, ultrasonography showed multiple millimetric stones in gallbladder, and due to symptomatic gallbladder disease, operation was performed under elective conditions. Surgery was in accordance with standards, and exploration of abdomen during operation found no pathology. Drain left in abdomen after Ulus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Yazar et al. A rare disease mimics postoperative bile leakage

operation was removed on first postoperative day with no significant output, and on second day, patient was discharged without problems. However, patient began to complain of bloating in succeeding days. Her complaints gradually increased, and she was hospitalized again on seventh postoperative day because of onset of nausea and vomiting. Medical treatment was initiated, but clinical tableau did not improve. Due to continued increase in intra-abdominal fluid and development of acute abdominal findings, patient was referred to our clinic on 19th day. Patient looked pale and dehydrated. Blood pressure was 125/70 mmHg, heart rate was 84/bpm and temperature was 37.2 °C. Abdominal examination revealed sensitivity and rigidity, particularly in RUQ. Laboratory analysis indicated moderate liver enzyme disorders: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were 1.5 times higher than normal, and alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) values were approximately 2 times higher. Bilirubin values and other biochemical parameters were normal. Patient intravenous (IV)/oral contrast abdominal computed tomography (CT) of abdomen revealed liquid advancing to left of abdominal midline, especially in subhepatic space, and well-circumscribed mass of about 10 cm was observed in left subhepatic area (Fig. 1). Decision was made to perform emergency operation due to acute abdominal symptoms, with presumptive diagnosis of biliary leakage, foreign object, and abscess. Laparoscopic incision line below umbilicus was reopened and laparoscopic trocar inserted to attempt exploration of abdomen. However, adequate field of view could not be achieved and laparotomy was performed with midline incision to enter abdomen. Exploration revealed about 1500 cc of yellow-green fluid, presumed to be bilious, present in subhepatic space, especially in right subhepatic space. Material with discoid appearance, approximately 10x10 cm in size and with gelatinous

Figure 1. Preoperative tomographic image of the patient.

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consistency found in left subhepatic space (Fig. 2). Considering patientâ&#x20AC;&#x2122;s previous surgery, bile duct injury was suspected. Cystic duct stump was found and clips were removed. Cystic duct was cannulated and intraoperative cholangiography was taken. Leakage was not observed on cholangiography. As a precautionary measure, a tube was inserted in cystic duct and external biliary drainage was provided. In postoperative period follow-up, clinical tableau resolved. Cholangiography was taken on the 21st day and as leakage was still not observed, drainage catheter was removed. Pathology result after examination of mass led to diagnosis of aspergillosis (Fig. 3a, b). Additional treatment was not recommended and patient was referred to infectious disease department.

DISCUSSION Aspergillus species can cause allergies and mycotoxicoses, as well as infections called aspergillosis. As the disease is generally seen in individuals with immune system disorders, and is created by infectious agents suspended in the air, it often leads to pulmonary infections. However, skin, adrenal glands, central nervous system (CNS), liver, spleen, and gastrointestinal system involvement can also be seen in individuals with immune system disorders. As in present case, in individuals with normal immune system, it has also been reported that IAA may develop as result of operating room sterilization problems.[2,3] Gastrointestinal presentation of invasive aspergillosis (IA) is unusual. In a study conducted by Hori et al. that examined an autopsy series, it was reported that small intestine-localized gastrointestinal system (GIS) aspergillosis was detected in 37 of 107 cases examined.[2] GIS aspergillosis, a form that has high mortality rates, is characterized by mesenteric artery invasion, intravascular thrombosis, and tissue ischemia. Clinical-

Figure 2. Image of fungus ball removed from the subhepatic space.

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Yazar et al. A rare disease mimics postoperative bile leakage

(a)

(b)

Figure 3. (a) The histopathological appearance of the mass removed from the subhepatic space, hypha structures branching with narrow angle in necrotic ground (H&E, x100). (b) More prominent appearance of the hypha in the PAS histochemical stain (PAS, x400).

ly, it can present with fever, abdominal pain, ileus, peritonitis, bloody diarrhea and hematochezia.[3] In addition, apart from gastrointestinal tract, urinary system may also be affected.[4] Literature survey indicated that the present case is first to develop after LC. Patient began to complain about bloating on second postoperative day, and 5 days later, nausea and vomiting were added to tableau. However, such findings can develop in all abdominal infections, so they cannot be expected to bring IA to mind.

A. fumigatus, which is responsible for 90% of cases of IA, has germination rate of 5–12 hours. It has been shown that with proper humidity and temperature, it can reach 4–8 times its normal size. As a result, it may take days or weeks for disease to colonize and emerge in patients.[4] For example, a disseminated disease was reported to occur in a 3-week period for a patient with heart transplantation, while in another laparotomy patient, period was 48 hours.[5] Routine laboratory tests and imaging performed at another medical center before operation on present patient revealed no pathological findings, other than cholelithiasis. Abdominal distention started 2 days after surgery, and clinically worsening patient was then referred to our hospital 19 days after operation. Although length of time required for aspergilli to multiply, proliferate, and disseminate disease varies, the onset of symptoms after 48 hours observed in present case, their progressive increase, and becoming very apparent in about 3 weeks correlates to GIS symptoms seen with aspergillosis. When patient underwent emergency operation, a mass of approximately 10x10 cm, well-circumscribed, yellow-green in color and of gelatinous consistency was observed in subhepatic space of abdomen and subsequently sent to pathology. There was also about 1500 cc of similarly colored liquid in the abdomen. Intraoperative bile leakage was considered and surgical treatment was applied. Fungi that are derivative of Aspergillus produce pigments with various colors.[6] In partic500

ular, it is known that some Aspergillus conidia produce green pigment. When we re-evaluated the patient retrospectively, we considered that pigment produced by the fungus may have caused the yellow-green color of the mass and that the greenish fluid in the abdomen had not been bile. Aspergilli may cause deep abdominal surgical infections, especially after construction or renovation work in hospitals, due to contamination of surgical instruments. In the present case, when we interviewed the surgeon who first operated on the patient, we learned that there were renovations ongoing in the hospital at that time. This also explains patient’s clinical picture. Additionally, lack of pathology observed in patient on physical examination, laboratory tests, and imaging before initial operation and progressive worsening of clinical tableau after the operation support idea that lesion occurred secondary to bad sterilization. Another important issue is early diagnosis of aspergillosis and starting appropriate treatment as soon as possible. Especially in patients with immune system disorders, this is of vital importance. Combined use of microscopic examination and culture results facilitates clinician’s diagnosis. However, it should be remembered that blood cultures of patients are rarely positive, and even in cases of pulmonary involvement, bronchoalveolar lavage (BAL) fluid culture is positive only in advanced patients; diagnosis is generally immediately before patient death. Kusne and al. reported in their study that even in pulmonary aspergillosis cases, 79% are reported in cultures. Therefore, in GIS aspergillosis, except for blood cultures, it is mostly diagnosed with biopsies and histological examination of biopsy material that was removed surgically. If we had thought the yellow-green fluid might have been due to aspergillosis, culture of the fluid might have helped. Invasive fungal infection such as aspergillosis may occur as result of improper sterilization conditions. It can be simply and effectively prevented with more attention to sterilization. EsUlus Travma Acil Cerrahi Derg, September 2016, Vol. 22, No. 5


Yazar et al. A rare disease mimics postoperative bile leakage

pecially in the presence of underlying predisposing condition, it should be kept in mind that these infections can imitate bile leakage, one of the common complications of LC, because of the pigments produced by such fungal infections. Conflict of interest: None declared.

REFERENCES 1. Hospenthal DR, Kwon-Chung KJ, Bennett JE. Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation. Med Mycol 1998;36:165–8.

2. Hori A, Kami M, Kishi Y, Machida U, Matsumura T, Kashima T. Clinical significance of extra-pulmonary involvement of invasive aspergillosis: a retrospective autopsy-based study of 107 patients. J Hosp Infect 2002;50:175–82. 3. Bizet J, Cooper CJ, Zuckerman MJ, Torabi A, Mendoza-Ladd A. A bleeding colonic ulcer from invasive Aspergillus infection in an immunocompromised patient: a case report. J Med Case Rep 2014;8:407. 4. Denning DW. Invasive aspergillosis. Clin Infect Dis 1998;26:781–803; quiz 804–5. 5. Carlson GL, Mughal MM, Birch M, Denning DW. Aspergillus wound infection following laparostomy. J Infect 1996;33:119–21. 6. Latgé JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 1999;12:310–50.

OLGU SUNUMU - ÖZET

Ameliyat sonrası safra kaçağını taklit eden nadir bir hastalık: İnvaziv aspergillozis Dr. Fatih Mehmet Yazar,1 Dr. Aykut Urfalıoğlu,2 Dr. Ömer Faruk Boran,2 Dr. Hamide Sayar,3 Dr. Burhan Hakan Kanat,4 Dr. Arif Emre,1 Dr. Emrah Cengiz,1 Dr. Ertan Bülbüloğlu1 Sütçü İmam Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Anestezi Anabilim Dalı, Kahramanmaraş 3 Sütçü İmam Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Kahramanmaraş 4 Elazığ Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Elazığ 1 2

Özellikle bağışıklık sisteminde sorun olan hastalarda ciddi enfeksiyonlara neden olan Aspergillus ailesi nadiren karıniçi enfeksiyonlara da neden olabilmektedir. Dış merkezde laparoskopik kolesistektomi ameliyatı olan ve ameliyat sonrası erken dönemde başlayarak, giderek artan şişkinlik, bulantı ve kusma şikayetleri olan hasta ameliyat sonrası 19. günde akut karın tanısı ile kliniğimize sevk edildi. Hasta, safra kaçağı düşünülerek ameliyat edildi, ancak eksplorasyonda suphepatik alanda bulunan sarı-yeşil renkte yumuşak kitlenin patolojik incelemesinde aspergilloz enfeksiyonuna bağlı fungus topu olduğu anlaşıldı. Ameliyat sonrası karın içi aspergillus tanısı alan 46 yaşındaki kadın hasta literatür eşliğinde sunuldu. Anahtar sözcükler: Ameliyat sonrası safra kaçağı; invaziv aspergillozis; laparoskopik kolesistektomi. Ulus Travma Acil Cerrahi Derg 2016;22(5):498–501

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Akut apandisiti taklit eden karın ön duvarı yerleşimli preperitoneal saplı lipom torsiyonu Dr. İbrahim Ali Özemir,1 Dr. Kıvılcım Orhun,1 Dr. Çağrı Bilgiç,1 Dr. Tunç Eren,1 Dr. Barış Bayraktar,1 Dr. Ebru Zemheri,2 Dr. Özgür Ekinci,1 Dr. Orhan Alimoğlu1 1

İstanbul Medeniyet Üniversitesi, Göztepe Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, İstanbul

2

İstanbul Medeniyet Üniversitesi, Göztepe Eğitim ve Araştırma Hastanesi, Patoloji Anabilim Dalı, İstanbul

ÖZET Lipomlar erişkinlerde adipöz dokunun en sık görülen benign tümörleridir. Vücudun heryerinde görülebilmekle beraber, karın içinde özellikle de preperitoneal bölgede nadiren saptanmaktadırlar. Genel olarak farklı patolojiler için yapılan inceleme ve ameliyat esnasında rastlantısal olarak tespit edilmelerine rağmen çok nadir olarak da lipomun kendisi akut karını taklit eden patolojilere yol açabilmektedir. Bu yazıda, akut apandisiti taklit eden bulgularla acile başvuran ve laparaskopik eksplorasyonda karın sağ alt kadranda preperitoneal yerleşimli torsiyone olmuş saplı lipom saptanan 35 yaşındaki kadın hasta literatür eşliğinde sunuldu. Anahtar sözcükler: Akut karın; karın duvarı lipomu; minimal invaziv cerrahi.

GİRİŞ

OLGU SUNUMU

Lipomlar yağ dokusunun iyi diferansiye, kapsüllü mezenkimal tümörleridir. Klinik olarak en sık 40–60 yaş arasında bulgu verirler. Soliter veya multiple olabilen lipomlar vücudun çeşitli bölgelerinde, nadiren de karın içinde bulunabilmektedirler. [1–4] Gastrointestinal sistemde lipomlar submukoza veya subserozal bölgede yerleşerek intusepsiyona yol açabilirler. Preperitoneal bölge saplı lipomu ise çok nadir görülmekte olup, literatürde torsiyon nedeniyle akut karın bulgusu oluşturan sadece dört vaka bildirilmiştir.[5–8]

Otuz beş yaşında kadın hasta, yaklaşık iki gün önce başlayan karın sağ alt kadran ağrısının artması üzerine acil polikliniğimize başvurdu. Özgeçmişinde özellik olmayan hastanın muayenesinde akut apandisit ile uyumlu olacak şekilde karın sağ alt kadranda hassasiyet ve rebound saptandı. Kan tahlillerinde WBC: 13.300 K/mm3, CRP: 4 mg/dl olarak tespit edildi. Yapılan karın ultrasonografisinde sağ alt kadranda, çekuma yapışık ve sınırları net ayırt edilemeyen, yaklaşık 4x2 cm boyutunda, nekroze lipom ile uyumlu lezyon saptandı. Hastaya akut karın ön tanısı ile diyagnostik laparaskopi kararı alındı. Göbekten yapılan insizyondan karbondioksit insüflasyonu sonrası 10 mm’lik trokar ile batına girildi. Eksplorasyonda karın sağ alt kadranda omentum tarafından sarılmış, çekum ön duvarına yapışık, ince bir sap ile karın ön duvar peritonuna asılı olduğu gözlenen, yüzeyi düzgün, kapsüllü, yaklaşık 4x2 cm’lik enflame ve ödemli kitle lezyonu tespit edildi (Şekil 1a, b). Suprapubik bölgeden 5 mm’lik ikinci bir trokar girildi. Kitlenin çekum ön duvarına yapıştığı ve burada enflamasyona yol açtığı görüldü. Paraçekal bölgede yaklaşık 40 cc reaksiyonel mayi saptanarak aspire edildi. Grasper yardımıyla kitlenin omentum ve çekumla olan yapışıklıkları ayrıştırıldı. Kitlenin karın ön duvarı peritonuna tutunduğu ince sapın etrafında dönerek torsiyone olduğu ve gangren geliştiği görüldü. Laparaskopik makas ile lezyonun sap kısmı koterize edilerek kesildi. 5 mm’lik teleskop ile suprapubik trokardan girildi ve lezyon 10 mm’lik trokardan endobag yardımıyla karın dışına alınıarak operasyon sonlandı-

Bu yazıda, karın sağ alt kadranda akut apandisiti taklit eden karın ağrısı bulguları ile acil servise başvuran ve tanısal laparaskopi sonucu karın sağ alt kadranda preperitoneal saplı lipom torsiyonu saptanan hasta sunuldu.

İletişim adresi: Dr. İbrahim Ali Özemir, Küçüksu Mah., Asma Sok, Eston Kandilli Evleri Sitesi, A12 Blok, D: 8, Kandilli, Üsküdar, İstanbul Tel: +90 505 - 803 21 25 E-mail: draliozemir@hotmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):502–504 doi: 10.5505/tjtes.2016.63500 Telif hakkı 2016 TJTES

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Özemir ve ark. Akut apandisiti taklit eden karın ön duvarı yerleşimli preperitoneal saplı lipom torsiyonu

(b)

(a)

(c)

Şekil 1. (a) Karın ön duvarına tutunmuş ve torsiyone olmuş saplı lipom. (b) Saplı lipomun yapıştığı çekumdan ayrılmış hali, apendiks ve çekum. (c) Lipomun eksize edilmiş hali.

ve tıkanıklığa yol açabilirler.[9] Malign transformasyon omuz, sırt veya retroperitoneal yerleşimli lipomlarda nadir olarak saptanmaktadır.[8] Primer peritoneal tümörler nadir olup, peritonun mezotelyal veya submezotelyal katmanlarından kaynaklanırlar. Karında rahatsızlık, şişkinlik, ağrı veya palpabl kitle ile kendilerini gösterebildikleri gibi, intraabdominal lipomların birçoğu farklı bir sebepten dolayı yapılan radyolojik inceleme veya ameliyat esnasında rastlantısal olarak saptanmaktadır. Çok nadiren olgumuzdaki gibi akut karına yol açabilirler.

rıldı (Şekil 1c). Ameliyat sonrası dönemde herhangi bir problem yaşanmayan hasta ikinci gün taburcu edildi. Rezeksiyon piyesinin histopatolojik incelemesinde dış yüzünde kapsülü izlenen matür yağ dokudan oluşan lipomatöz lezyon izlenmiştir. Lezyonda birçok alanda eski ve yeni kanama odakları, nötrofillerin eşlik ettiği akut enflamasyon dikkati çekmiştir (Şekil 2).

TARTIŞMA Lipomlar yumuşak dokunun en sık rastlanan benign tümörleri olup, genellikle mobil ve ağrısız kitleler olarak görülürler. Büyük çoğunluğu semptom oluşturmadığından gerçek prevalansı tam olarak bilinmemektedir. Lipom gelişiminde ailesel yatkınlığın yanısıra, obezite, diyabet, hiperkolesterolemi ve travmatik yaralanmaların rol oynadığı düşünülmektedir.[4] Lipomların yarısından fazlası subkutanöz bölgede lokalize olup, ciddi bir sağlık problemi yaratmazlar. İntraabdominal yerleşimli lipomlar ise gastrointestinal sistemde kanama, ülserasyon

(a)

Radyolojik olarak en duyarlı inceleme bilgisayarlı tomografidir. [10,11] Ancak deneyimli ellerde ultrasonografi de yüksek tanısal değere sahiptir. Ultrasonografik olarak lipomlar ekojenik kapsülle çevrili izo-hiperekoik lezyonlar olup, çevre dokuları penetre etmeyen, yumuşak ve mobil kitleler olarak saptanırlar. [12] Olgumuzda yapılan ultrasonografide de 4x2 cm boyutunda nekroze lipom ile uyumlu lezyon tespit edilerek eksplorasyon kararı alındı.

(b)

Şekil 2. Lipomun (a) makroskobik ve (b) mikroskobik görünümü: Kapsüllü (ok) matür yağ dokuda hemoraji, akut enflamasyon odakları (çift başlı ok) (Hematoksilen & Eozin x 40).

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Akut karın ağrısı acil servise başvuruların yaklaşık %5–10’unu teşkil etmekte ve bunların büyük çoğunluğunu akut apandisit oluşturmaktadır.[13] Apandektomi uygulanan hastaların %20 –30’unda normal apandis saptanmaktadır.[14] Akut apandisitle karışabilen veya onu taklit eden tuba-overyal patolojiler, üriner sistem patolojileri, Ailesel Akdeniz Ateşi, Crohn hastalığı, gastrointestinal sistem perforasyonları gibi birçok patoloji mevcuttur. Olgumuzdaki gibi preperitoneal saplı lipom torsiyonuna bağlı akut karına sebep olan gangrene lipom literatürde sadece dört hastada bildirilmiştir.[5–8] Barut ve ark. [5] eksploratif laparatomi yaptıkları olgularında median umblikal ligament hizasında parietal periton saplı lipomuna bağlı akut karın geliştiğini belirtmişler. Yayınlanan diğer üç olguda ise bizim olgumuzdaki gibi akut apandisiti taklit eden, sağ alt kadranda torsiyone karın ön duvarı lipomu nedeniyle laparaskopik eksplorasyon uygulanmıştır.[6–8] Bunker ve ark.[6] laparokopik eksplorasyon yaptıkları olguda torsiyone lipoma eşlik eden ikincil bir karın duvarı lipomu daha bildirmişler. Akut appendisit şüphesi olan hastalarda laparoskopik eksplorasyon sayesinde mevcut veya eşlik eden diğer patolojilerin tanı ve tedavisi de mümkün olmaktadır.[15] Biz de olgumuzda laparasopik eksplorasyon esnasında torsiyone lipomu tespit ederek, sadece iki trokar girişi kullanarak lezyonun eksizyonunu gerçekleştirdik. Sonuç olarak, akut apandisiti düşündüren sağ alt kadran ağrılarında, nadir olmakla birlikte torsiyone saplı lipomlar da ayırıcı tanı içinde yer almalıdır. Akut apandisit şüphesiyle operasyon planlanan hastalarda diagnostik laparoskopi uygulanması, karın duvarının eksplorasyonuna imkan vermesi sayesinde farklı patolojilerin saptanmasını ve minimal invaziv olarak tedavi edilmesini sağlamaktadır. Laparoskopik yaklaşım geniş karın insizyonlarının ve ikincil cerrahi girişimlerin engellemesi açısından özellikle bu tür olgularda önem taşımaktadır. Çıkar örtüşmesi: Çıkar örtüşmesi bulunmadığı belirtilmiştir.

KAYNAKLAR 1. Prando A, Wallace S, Marins JL, Pereira RM, de Oliveira ER, Alvarenga

M. Sonographic features of benign intraperitoneal lipomatous tumors in children-report of 4 cases. Pediatr Radiol 1990;20:571–4. 2. Kaniklides C, Frykberg T, Lundkvist K. Paediatric mesenteric lipoma, an unusual cause of repeated abdominal pain. A case report. Acta Radiol 1998;39:695–7. 3. Takagi Y, Yasuda K, Nakada T, Abe T, Saji S. Small bowel volvulus caused by a lipoma of the mesentery showing a distinct pattern on preoperative computed tomography. Dis Colon Rectum 1998;41:122–3. 4. Ilhan H, Tokar B, Işiksoy S, Koku N, Pasaoglu O. Giant mesenteric lipoma. J Pediatr Surg 1999;34:639–40. 5. Barut I, Tarhan OR, Cerci C, Ciris M, Tasliyar E. Lipoma of the parietal peritoneum: an unusual cause of abdominal pain. Ann Saudi Med 2006;26:388–90. 6. Bunker DL, Ilie VG, Halder TK. Torsion of an abdominal-wall pedunculated lipoma: a rare differential diagnosis for right iliac fossa pain. Case Rep Surg 2013;2013:587380. 7. Shrestha BB, Karmacharya M. Torsion of a lipoma of parietal peritoneum: a rare case mimicking acute appendicitis. J Surg Case Rep 2014;2014(6). 8. Sathyakrishna BR, Boggaram SG, Jannu NR3. Twisting lipoma presenting as appendicitis-a rare presentation. J Clin Diagn Res 2014;8:ND07– 8. 9. Cha JM, Lee JI, Joo KR, Choe JW, Jung SW, Shin HP, et al. Giant mesenteric lipoma as an unusual cause of abdominal pain: a case report and a review of the literature. J Korean Med Sci 2009;24:333–6. 10. Pereira JM, Sirlin CB, Pinto PS, Casola G. CT and MR imaging of extrahepatic fatty masses of the abdomen and pelvis: techniques, diagnosis, differential diagnosis, and pitfalls. Radiographics 2005;25:69–85. 11. Méndez-Uriburu L, Ahualli J, Méndez-Uriburu J, Méndez-Uriburu M, Fajre L, Méndez-Uriburu F, et al. CT appearances of intraabdominal and intrapelvic fatty lesions. AJR Am J Roentgenol 2004;183:933–43. 12. Truong S, Pfingsten FP, Dreuw B, Schumpelick V. Value of sonography in diagnosis of uncertain lesions of the abdominal wall and inguinal region. [Article in German] Chirurg 1993;64:468–75. [Abstract] 13. Sanson TG, O’Keefe KP. Evaluation of abdominal pain in the elderly. Emerg Med Clin North Am 1996;14:615–27. 14. Walczak DA, Pawełczak D, Żółtaszek A, Jaguścik R, Fałek W, Czerwińska M, et al. The Value of Scoring Systems for the Diagnosis of Acute Appendicitis. Pol Przegl Chir 2015;87:65–70. 15. Tsushimi T, Matsui N, Kurazumi H, Takemoto Y, Oka K, Seyama A, et al. Laparoscopic resection of an ileal lipoma: Report of a case. Surg Today 2006;36:1007–11.

CASE REPORT - ABSTRACT

Torsion of a preperitoneal pedunculated lipoma of anterior abdominal wall mimicking acute appendicitis İbrahim Ali Özemir, M.D.,1 Kıvılcım Orhun, M.D.,1 Çağrı Bilgiç, M.D.,1 Tunç Eren, M.D.,1 Barış Bayraktar, M.D.,1 Ebru Zemheri, M.D.,2 Özgür Ekinci, M.D.,1, Orhan Alimoğlu, M.D.,1 1 2

Department of General Surgery, İstanbul Medeniyet University, Göztepe Training and Research Hospital, İstanbul-Turkey Department of Pathology, İstanbul Medeniyet University, Göztepe Trainig and Research Hospital, İstanbul-Turkey

Lipoma is the most common benign tumor of adipose tissue. Lipomas can occur almost anywhere in the body, but are rarely found in parietal peritoneum of abdominal wall. Occasionally lipomas are detected incidentally during abdominal surgery for other organ pathologies. Presently described is rare case of torsion of pedunculated lipoma originating in parietal peritoneum of anterior abdominal wall causing abdominal pain that mimicked acute appendicitis in 35-year-old woman. Keywords: Abdominal wall lipoma; acute abdominal pain; minimally invasive surgery. Ulus Travma Acil Cerrahi Derg 2016;22(5):502–504

504

doi: 10.5505/tjtes.2016.63500

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OLGU SUNUMU

Süt çocuğunda anorektal cerrahi sonrası gelişen Fournier gangreni: İki olgu sunumu Dr. Murat Sütçü,1 Dr. Güntulu Duran Şık,2 Dr. Feryal Gün,3 Dr. Ayper Somer,1 Dr. Nuran Salman1 1

İstanbul Üniversitesi İstanbul Tıp Fakültesi, Çocuk Enfeksiyon Bilim Dalı, İ̇stanbul-Turkey

2

İstanbul Üniversitesi İstanbul Tıp Fakültesi, Çocuk Yoğun Bakım Bilim Dalı, İstanbul-Turkey

3

İstanbul Üniversitesi İstanbul Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, İstanbul-Turkey

ÖZET Nekrotizan fasiit, deri, subkutan dokular ve fasyaların ilerleyici nekrozu ile karakterize, yaşamı tehdit eden bir yumuşak doku enfeksiyonudur. Fournier gangreni (FG), perianal ve genital bölgenin tutulduğu nekrotizan fasitin ciddi ve agresif bir şeklidir. Burada anorektal cerrahi sonrası çevre dokuda yaygın nekroz gelişen ve septik şoka neden olan iki FG olgusu sunuldu. Olgu 1: Öyküsünde anal darlık ve duplikasyon yapılan altı aylık kız hasta ateş, uykuya meyil ve emmeme yakınmaları ile başvurdu. Fiziksel incelemede anal bölgede ekimoz olan hasta septik şok bulgularıyla yoğun bakım ünitesi’ne (YBÜ) alındı. Uygun antibiyotik tedavisi başlanan hastanın on iki saat içerisinde lezyonun nekrotik hale gelmesi üzerine acil cerrahi debridman uygulandı. Kan ve doku kültürleri negatif saptanan hastada başvurudan itibaren iki ay içerisinde tam iyileşme saptandı. Olgu 2: Dokuz aylık erkek hasta fistülotomiden sekiz saat sonra dirençli nöbet ve septik şok bulguları ile YBÜ’ye yatırıldı. Fiziksel incelemede skrotal, gluteal ve perianal bölgede ödem ve ekimoz gözlendi. Septik şoktaki hastaya temel yaşam desteği verildikten sonra geniş spektrumlu antibiyotik tedavisi başlandı ve perianal debridman yapılarak kolostomi açıldı. Tamamen düzelme hiperbarik oksijen tedavisi sonrası başvurunun üçüncü ayında sağlandı. Anoraktal cerrahi uygulanan her hasta FG açısından dikkatle izlenmelidir. Erken debridman, uygun antibiyotik tedavisi ve hiperbarik oksijen tedavisi hayat kurtarıcı olabilir. Anahtar sözcükler: Anorektal cerrahi; Fournier’s gangreni; süt çocuğu.

GİRİŞ Nekrotizan yumuşak doku enfeksiyonu, deri, subkutan dokular ve fasyaların ilerleyici nekrozu ile karakterize çocuklarda nadir görülen bir durumdur. En hızlı ilerleyen yumuşak doku enfeksiyonu olup tedaviye rağmen mortalite ve morbiditesi yüksektir.[1,2] İlk kez Baurienne tarafından 1764’te tanımlanmış olup Jaen Alfred Fournier’in 1883’te tanımladığı genital organlar ve perineyi tutan yumuşak doku enfeksiyon tablosuna ise Fournier gangreni (FG) denilmiştir.[3] Nekrotizan yumuşak doku enfeksiyonu gelişiminde cerrahi müdahale, abrazyon, kontüzyon, penetran travma, enjeksiyon, İletişim adresi: Dr. Murat Sütçü, İstanbul Üniversitesi İstanbul Tıp Fakültesi, Çoçuk Enfeksiyon Hastalıkları Bilim Dalı, Çapa, Fatih, İstanbul Tel: +90 212 - 414 22 00 / 32566 E-mail: sutcu13@yahoo.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg 2016;22(5):505–508 doi: 10.5505/tjtes.2015.45675 Telif hakkı 2016 TJTES

Ulus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5

perianal abse, inkarsere fıtık ve yanık gibi bir çok altta yatan durum saptanmıştır. Buna karşın hiçbir risk faktörü olmadan da gelişebileceği bildirilmiştir.[4] Nekrotizan yumuşak doku enfeksiyonu bir veya daha fazla etkene bağlı gelişebilir. Çok kısa sürede geniş doku kaybı, bakteriyemi, çoklu organ yetersizliği, şok ve ölümle sonuçlanır. Erken tanı çok önemli olup beraberinde agresif cerrahi debridman ve uygun antibiyotik kullanımı hastalığın tedavisine olanak sağlar. Buna karşın erken tanı ve uygun tedaviye rağmen doku hatta ekstremite kaybı ve sistemik komplikasyon gelişimi sıktır.[5] Hiperbarik oksijen tedavisi hastalığın ilerlemesi sonucu geniş debridman yapılan olgularda yara iyileşmesinde etkilidir.[6] Bu yazıda, anorektal cerrahi sonrası FG gelişip erken debridman, uygun antibiyotik ve hiperbarik oksijen tedavileri ile tamamen iyileşen iki süt çocuğu olgusu sunuldu.

OLGU SUNUMU Olgu 1 Altı aylık kız hasta ateş, uykuya meyil ve emmeme yakınmaları ile çocuk acil polikliniğine başvurdu. Hastanın öyküsünde anal darlık ve duplikasyon nedeniyle sekiz saat önce anal dilatasyon işlemi yapıldığı öğrenildi. Fiziksel incelemede 505


Sütçü ve ark. Süt çocuğunda anorektal cerrahi sonrası gelişen Fournier gangreni

bilinci kapalı, taşikardik, solunumu yüzeyel olup taşipneik, hipotansif, kapiller dolum zamanı uzamış ve ateşinin olduğu saptandı. Septik şok tablosunda olan hastanın anal bölgede ekimozu mevcuttu. Çocuk yoğun bakım ünitesine alınan hasta entübe edilip agresif sıvı tedavisi ile inotropik destek başlandı. Laboratuvar incelemelerinde lökosit sayımı 4120 mm³, mutlak nötrofil sayımı: 2160 mm³, trombosit sayımı: 412.500 mm³, C-reaktif protein: 66.2 mg/L, prokalsitonin: 440 ng/ml idi. Biyokimyasal incelemede hiponatremi ve uzamış INR saptandı. Hastanın tüm kültürleri alınarak ampirik teikoplanin ve meropenem tedavisi başlandı. İzleminin 12. saatinde anal bölgedeki ekimozun renginin değiştiği ve sağ gluteal bölgeye yayıldığı görüldü. Karın tomografisinde sigmoid kolonda daha belirgin olmak üzere bağırsak anslarında genişleme, karın içi serbest sıvı ve anal sfinkterde lokalize laserasyon saptandı. Fournier gangreni olarak değerlendirilen hasta 24. saatinde acil operasyona alınarak sağ glutael cilt, cilt altı, fasya ve yağ dokusu debride edildi ve kolostomi açıldı. İzleminin altıncı gününde yara yerinde nekrotik dokuların oluşması nedeniyle ikinci kez debridman yapıldı. Hiperbarik oksijen tedavisi gün aşırı olarak beş kez uygulanan hastanın yara yeri tamamen kapandı. Kültürleri steril sonuç veren hastanın antibiyoterapisi 21 güne tamamlanarak kesildi.

Olgu 2 Perianal fistül nedeniyle fistülektomi operasyonu yapılan dokuz aylık erkek hasta işlemden sekiz saat sonra ateş, bilinç bulanıklığı ve nöbet geçirme yakınmaları ile çocuk yoğun bakım ünitesine kabul edildi. Skrotal, sol gluteal ve perianal bölgede ödem, ekimoz ve geçirilmiş operasyona bağlı dikiş bulunan hastanın bilinci kapalı olup taşikardi, taşipne, hipotansiyon ve hepatomegalisi mevcuttu. Septik şok tablosunda olan hasta

Şekil 2. İkinci olgunun başvuru, debridman ve sonrasındaki yara yeri görüntüleri.

entübe edilip agresif sıvı tedavisi ile inotropik destek tedavisi verildi. Tüm kültürleri alınarak ampirik teikoplanin, meropenem ve amikasin başlandı. Laboratuvar incelemelerinde lökosit sayımı 3200 mm³, mutlak nötrofil sayımı: 1610 mm³, trombosit sayımı: 71.500 mm³, C-reaktif protein: 419 mg/L, prokalsitonin: 523 ng/ml olup ayrıca hipoglisemi ve hiponatremisi mevcuttu. Hastanın tüm kültürleri alınarak ampirik teikoplanin, meropenem ve amikasin tedavileri başlandı. Kısa sürede anogenital bölgedeki ekimoz alanlarında genişleme ve renk değişikliği görüldü. Karın görüntülemesinde karın alt kadran ve perianal bölgede cilt altı ödem, sıvı koleksiyonu ve enflame alanlar mevcuttu. Fournier gangreni olarak değerlendirilen hastada eş zamanlı olarak ileri derecede karın distansiyonu ve karıniçi basınç artışı saptandı. Ağır septik şok, kompartman sendromu ve oligüri gelişen hastaya hemodiyafiltrasyon yapıldı. Hemodinamisi ve genel durumu stabil hale gelen hastanın izleminin dördüncü gününde perianal debridman yapılıp sigmoid saptırıcı kolostomi açıldı. İzlemin 14. gününde nekrotik dokuların temizlenmesi amacıyla ikinci kez debridman yapıldı. Hiperbarik oksijen tedavisi başlanan hastanın yara yerinde hızlı bir iyileşme görüldü. Toplam 10 kez gün aşırı hiperbarik oksijen tedavisi alan hastanın yara yeri tamamen kapandı. Kültürleri steril sonuçlanması üzerine antibiyoterapisi teikoplanin 21, meropenem 25 ve amikasin 14. gününde iken sonlandırıldı.

TARTIŞMA Şekil 1. Birinci olgunun başvuru, debridman ve sonrasındaki yara yeri görüntüleri.

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Fournier gangreni genital ve perianal bölgede polimikrobiyal enfeksiyöz etkenlere bağlı gelişen nekrotizan yumuşak doku enfeksiyonunun en ciddi ve agresif formudur.[7] Çoğunlukla Ulus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5


Sütçü ve ark. Süt çocuğunda anorektal cerrahi sonrası gelişen Fournier gangreni

30–60 yaş arası erkeklerin bir hastalığı olup çocuk popülasyonda nadirdir.[8,9] Çocuk hastalarda ise en sık süt çocukluğu döneminde karşımıza çıkmaktadır. Bizim olgularımız da çocuk literatürlerine benzer şekilde bir yaş altındaydı. Çocuk yaş grubunda risk faktörleri arasında travma, cerrahi, perianal bölge invaziv işlemleri (anal dilatasyon), yanık, su çiceği, üretral aletler, perianal deri apseleri ve omfalit yer alır.[10] Perianal cerrahi ve anal dilatasyon bizim hastalarımızda bulunan etiyolojik faktörlerdi.

gününde yapıldı. Her iki olguda da nekrotik dokuların uzaklaştırılması amacıyla ikinci bir debridman gereksinimi oldu.

Bakterilerin salgıladığı kollejanaz, hyaluronidaz gibi enzimlerin sinerjistik etkisiyle faysa dokusuna invazyonu sonucu vasküler tromboza yol açarak cilt ve cilt altında gangrene neden olurlar. Gangrene alan bakteri çoğalmasına uygun ortam sağlar. Enfeksiyon yüzeyel perineal fasyadan ilerleyerek genital organlar, batın ön duvarı, gluteal bölgeye yayılabilir.[11] Hastalığın ilk olguda perianal bölgeden başlayıp arkaya doğru gluteal bölgeye, ikinci olguda ise öne doğru skrotum ve karın ön duvarına ilerlediği görüldü.

Sonuç

Tanıda klinik şüphe önemli yer tutar. Laboratuvar bulguları non spesifik olup genellikle lökositoz ve C-reaktif proteinde yükseklik görülür. Ağır septik şok tablolarında bizim hastalarımızda olduğu gibi lökopeni gelişebilir. Radyolojik bulgular tanı koydurucu olmamakla beraber cilt altı dokularda ödem, enflamasyon ve gaz saptanması tanıyı destekler.[11]

KAYNAKLAR

Fournier gangreni bir veya daha fazla etkene bağlı gelişebilir. Etkenler genellikle streptekok, stafilokok ve anaerop bakterilerdir.[1] Hastalarımızın kültürleri steril sonuçlandı ve bu durum cerrahi girişimler sırasında yapılan antibiyotik profilaksisine bağlandı. Antibiyotik seçiminde hastaların septik şokta olması, perianal bölge girişim öyküsü ve nazokomiyal etkenler ön planda tutuldu. Gram pozitif, gram negatif ve anaerob etkenleri kapsayacak şekilde ampirik teikoplanin ile meropenem tedavisi uygulandı. Fournier gangreni çok kısa sürede geniş doku kaybı, bakteriyemi, çoklu organ yetersizliği, şok ve ölümle sonuçlanır. İki olgumuzda başvuru esnasında septik şokta tablosundaydı. Tedavide en önemli nokta erken ve yaygın cerrahi eksplorasyon ile tüm nekrotik dokuların kanlanmanın iyi olduğu seviyeye kadar debridmanıdır.[11] Olgularımızın birinde ilk 24 saat içerisinde cerrahi debridman yapılırken diğer olguda ise erken tanı almasına rağmen ancak genel durumun stabil olduğu dördüncü

Ulus Travma Acil Cerrahi Derg, Eylül 2016, Cilt. 22, Sayı. 5

Hiberbarik oksijen tedavisi nekrotizan fasiit olgularında son yıllarda daha sık kullanılmakta olup enfeksiyon kontrolü ve yara iyileşmesine olumlu etkileri gösterilmiştir.[12] İki olgumuzda da ikinci debridman sonrası hiperbarik oksijen tedavisi uygulandı. Yara alanı deri grefti veya flep gereksinimi olmadan tamamen iyileşti.

Anoraktal cerrahi uygulanan özellikle süt çocuklarında FG açısından dikkatli olunmalıdır. Tanıda şüphe önemli yer tutmakta olup erken tanı, uygun antibiyotik tedavisi ve erken cerrahi hayat kurtarıcıdır. Geniş debridman uygulanan hastalarda hiperbarik oksijen tedavisi doku grefti veya flep gereksinimini azaltabilir. Çıkar örtüşmesi: Çıkar örtüşmesi bulunmadığı belirtilmiştir.

1. Jamal N, Teach SJ. Necrotizing fasciitis. Pediatr Emerg Care 2011;27:1195–9; quiz 1200–2. 2. Bingöl-Koloğlu M, Yildiz RV, Alper B, Yağmurlu A, Ciftçi E, Gökçora IH, et al. Necrotizing fasciitis in children: diagnostic and therapeutic aspects. J Pediatr Surg 2007;42:1892–7. 3. Vayvada H, Demirdöver C, Menderes A, Karaca C. Necrotizing fasciitis: diagnosis, treatment and review of the literature. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2012;18:507–13. 4. Cainzos M, Gonzalez-Rodriguez FJ. Necrotizing soft tissue infections. Curr Opin Crit Care 2007;13:433–9. 5. Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg 2014;101:119–25. 6. Jallali N, Withey S, Butler PE. Hyperbaric oxygen as adjuvant therapy in the management of necrotizing fasciitis. Am J Surg 2005;189:462–6. 7. Yaghan RJ, Al-Jaberi TM, Bani-Hani I. Fournier’s gangrene: changing face of the disease. Dis Colon Rectum 2000;43:1300–8. 8. Ekingen G, Isken T, Agir H, Oncel S, Günlemez A. Fournier’s gangrene in childhood: a report of 3 infant patients. J Pediatr Surg 2008;43:39–42. 9. Eke N. Fournier’s gangrene: a review of 1726 cases. Br J Surg 2000;87:718–28. 10. Mallikarjuna MN, Vijayakumar A, Patil VS, Shivswamy BS. Fournier’s Gangrene: Current Practices. ISRN Surg 2012;2012:942437. 11. Bains SP, Singh V, Gill MK, Jain A, Arry V. Fournier’s Gangrene in a Two Year Old Child: A Case Report. J Clin Diagn Res 2014;8:ND01–2. 12. Levett D, Bennett MH, Millar I. Adjunctive hyperbaric oxygen for necrotizing fasciitis. Cochrane Database Syst Rev 2015;1:CD007937.

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CASE REPORT - ABSTRACT

Fournier’s gangrene after anorectal surgery in infant: Two case reports Murat Sütçü, M.D.,1 Güntulu Duran Şık, M.D.,2 Feryal Gün, M.D.,3 Ayper Somer, M.D.,1 Nuran Salman, M.D.1 1 2 3

Department of Pediatric Infectious Diseases, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey Department of Pediatric Intensive Care, İstanbul University Istanbul Faculty of Medicine, İstanbul-Turkey Department of Pediatric Surgery, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

Necrotizing fasciitis is a life-threatening soft tissue infection characterized by progressive necrosis of the skin, subcutaneous tissues and fascia. Fournier’s gangrene (FG) is a serious and aggressive form of infective necrotizing fasciitis involving perineal region and genitalia. Presently described are 2 pediatric cases of FG with widespread necrosis of surrounding tissue following anorectal surgery, causing severe septic shock. Case 1: Sixmonth-old female patient with anal stenosis and duplication presented at emergency clinic with fever, somnolence, irritability, and feeding difficulty. Physical examination upon admission to Intensive Care Unit (ICU) with septic shock determined she had ecchymosis in anal region. At 12fth hour after admission, lesion had become necrotic and patient was started on broad-spectrum antibiotics after surgical debridement. Cultures were negative and patient had complete recovery 2 months after admission.
Case 2: Nine-month-old male patient was admitted to ICU for convulsions and sepsis eight hours after fistulectomy. Scrotal, gluteal, and perianal edema and ecchymosis were observed on physical examination. Perianal debridement and colostomy were performed, and patient was given broad-spectrum antibiotics after basic life support strategies for septic shock. Complete recovery was achieved after hyperbaric oxygen treatment for perianal lesion and patient was discharged from the hospital in third month after admission.
After anorectal surgery, every patient should be observed carefully for FG. Early debridement, proper antibiotics, and hyperbaric oxygen treatment can be life-saving. Keywords: Anorectal surgery; Fournier’s gangrene; infant. Ulus Travma Acil Cerrahi Derg 2016;22(5):505–508

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doi: 10.5505/tjtes.2015.45675

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TRAUMA 2016 / 5  
TRAUMA 2016 / 5