Travma 2013 4

Cilt - Volume 19

Sayı - Number 4

Temmuz - July 2013

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY

www.tjtes.org Index Medicus, Medline, EMBASE/Excerpta Medica, Science Citation Index-Expanded (SCI-E), Index Copernicus ve TÜBİTAK-ULAKBİM Türk Tıp Dizini’nde yer almaktadır.

Indexed in Index Medicus, Medline, EMBASE/Excerpta Medica and Science Citation Index-Expanded (SCI-E), Index Copernicus and the Turkish Medical Index of TÜB‹TAK-ULAKB‹M.

ISSN 1306 - 696x

ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ TURKISH JOURNAL OF TRAUMA AND EMERGENCY SURGERY Editör (Editor) Recep Güloğlu Yardımcı Editörler (Associate Editors) Kaya Sarıbeyoğlu Hakan Yanar M. Mahir Özmen Geçmiş Dönem Editörleri (Former Editors) Ömer Türel Cemalettin Ertekin Korhan Taviloğlu

ULUSAL BİLİMSEL DANIŞMA KURULU (NATIONAL EDITORIAL BOARD) Fatih Ağalar Yılmaz Akgün Levhi Akın Alper Akınoğlu Murat Aksoy Şeref Aktaş Ali Akyüz Ömer Alabaz Orhan Alimoğlu Nevzat Alkan Edit Altınlı Acar Aren Gamze Aren Cumhur Arıcı Oktar Asoğlu Ali Atan Bülent Atilla Levent Avtan Yunus Aydın Önder Aydıngöz Erşan Aygün Mois Bahar Akın Eraslan Balcı Emre Balık Umut Barbaros Semih Baskan M Murad Başar Mehmet Bayramiçli Ahmet Bekar Orhan Bilge Mustafa Bozbuğa Mehmet Can Başar Cander Nuh Zafer Cantürk Münacettin Ceviz Banu Coşar Figen Coşkun İrfan Coşkun Nahit Çakar Adnan Çalık Fehmi Çelebi Gürhan Çelik Oğuz Çetinkale M. Ercan Çetinus Sebahattin Çobanoğlu Ahmet Çoker Cemil Dalay Fatih Dikici Yalım Dikmen Osman Nuri Dilek Kemal Dolay Levent Döşemeci Murat Servan Döşoğlu Kemal Durak Engin Dursun

İstanbul Çanakkale İstanbul Adana İstanbul İstanbul İstanbul Adana İstanbul İstanbul İstanbul İstanbul İstanbul Antalya İstanbul Ankara Ankara İstanbul İstanbul İstanbul İstanbul İstanbul Elazığ İstanbul İstanbul Ankara Kırıkkale İstanbul Bursa İstanbul Edirne İstanbul Konya Kocaeli Erzurum İstanbul Ankara Edirne İstanbul Trabzon Sakarya İstanbul İstanbul İstanbul Edirne İzmir Adana İstanbul İstanbul Sakarya Antalya Antalya Düzce Bursa Ankara

Atilla Elhan Mehmet Eliçevik İmdat Elmas Ufuk Emekli Haluk Emir Yeşim Erbil Şevval Eren Hayri Erkol Metin Ertem Mehmet Eryılmaz Figen Esen Tarık Esen İrfan Esenkaya Ozlem Evren Kemer Nurperi Gazioğlu Fatih Ata Genç Alper Gökçe Niyazi Görmüş Feryal Gün Ömer Günal Nurullah Günay Haldun Gündoğdu Mahir Günşen Emin Gürleyik Hakan Güven İbrahim İkizceli Haluk İnce Fuat İpekçi Ferda Şöhret Kahveci Selin Kapan Murat Kara Hasan Eşref Karabulut Ekrem Kaya Mehmet Yaşar Kaynar Mete Nur Kesim Yusuf Alper Kılıç Haluk Kiper Hikmet Koçak M Hakan Korkmaz Güniz Meyancı Köksal Cüneyt Köksoy İsmail Kuran Necmi Kurt Mehmet Kurtoğlu Nezihi Küçükarslan İsmail Mihmanlı Mehmet Mihmanlı Köksal Öner Durkaya Ören Hüseyin Öz Hüseyin Özbey Faruk Özcan Cemal Özçelik İlgin Özden Mehmet Özdoğan

Ankara İstanbul İstanbul İstanbul İstanbul İstanbul Diyarbakır Bolu İstanbul Ankara İstanbul İstanbul İstanbul Ankara İstanbul İstanbul Tekirdağ Konya İstanbul Düzce Kayseri Ankara Adana Bolu İstanbul İstanbul İstanbul İzmir Bursa İstanbul Ankara İstanbul Bursa İstanbul Samsun Ankara Eskişehir Erzurum Ankara İstanbul Ankara İstanbul İstanbul İstanbul Ankara İstanbul İstanbul İstanbul Erzurum İstanbul İstanbul İstanbul Diyarbakır İstanbul Ankara

Şükrü Özer Halil Özgüç Ahmet Özkara Mahir Özmen Vahit Özmen Niyazi Özüçelik Süleyman Özyalçın Emine Özyuvacı Salih Pekmezci İzzet Rozanes Kazım Sarı Esra Can Say Ali Savaş İskender Sayek Tülay Özkan Seyhan Gürsel Remzi Soybir Yunus Söylet Erdoğan Sözüer Mustafa Şahin Cüneyt Şar Mert Şentürk Feridun Şirin İbrahim Taçyıldız Gül Köknel Talu Ertan Tatlıcıoğlu Gonca Tekant Cihangir Tetik Mustafa Tireli Alper Toker Rıfat Tokyay Salih Topçu Turgut Tufan Fatih Tunca Akif Turna Zafer Nahit Utkan Ali Uzunköy Erol Erden Ünlüer Özgür Yağmur Müslime Yalaz Serhat Yalçın Sümer Yamaner Mustafa Yandı Nihat Yavuz Cumhur Yeğen Ebru Yeşildağ Hüseyin Yetik Cuma Yıldırım Bedrettin Yıldızeli Sezai Yılmaz Kaya Yorgancı Coşkun Yorulmaz Tayfun Yücel

Konya Bursa İstanbul Ankara İstanbul İstanbul İstanbul İstanbul İstanbul İstanbul İstanbul İstanbul Ankara Ankara İstanbul Tekirdağ İstanbul Kayseri Tokat İstanbul İstanbul İstanbul Diyarbakır İstanbul Ankara İstanbul İstanbul Manisa İstanbul İstanbul Kocaeli Ankara İstanbul İstanbul Kocaeli Urfa İzmir Adana İstanbul İstanbul İstanbul Trabzon İstanbul İstanbul Tekirdağ İstanbul Gaziantep İstanbul Malatya Ankara İstanbul İstanbul

ULUSLARARASI BİLİMSEL DANIŞMA KURULU INTERNATIONAL EDITORIAL BOARD

Juan Asensio Zsolt Balogh Ken Boffard Fausto Catena Howard Champion Elias Degiannis Demetrios Demetriades Timothy Fabian Rafi Gürünlüoğlu Clem W. Imrie Kenji Inaba Rao Ivatury Yoram Kluger Rifat Latifi Sten Lennquist Ari Leppaniemi Valerie Malka Ingo Marzi Kenneth L. Mattox Carlos Mesquita

Miami, USA New Castle, Australia Johannesburg, S. Africa Bologna, Italy Washington DC, USA Johannesburg, S. Africa Los Angeles, USA Memphis, USA Denver, USA Glasgow, Scotland Los Angeles, USA Richmond, USA Haifa, Israel Tucson, USA Malmö, Sweden Helsinki, Finland Sydney, Australia Frankfurt, Germany Houston, USA Coimbra, Portugal

Ernest E Moore Pradeep Navsaria Andrew Nicol Hans J Oestern Andrew Peitzman Basil A Pruitt Peter Rhee Pol Rommens William Schwabb Michael Stein Spiros Stergiopoulos Michael Sugrue Otmar Trentz Donald Trunkey Fernando Turegano Selman Uranues Vilmos Vecsei George Velmahos Eric J Voiglio Mauro Zago

Denver, USA Cape Town, S. Africa Cape Town, S. Africa Celle, Germany Pittsburgh, USA San Antonio, USA Tucson, USA Mainz, Germany Philadelphia, USA Petach-Tikva, Israel Athens, Greece Liverpool, Australia Zurich, Switzerland Oregon, USA Madrid, Spain Graz, Austria Vienna, Austria Boston, USA Lyon, France Milan, Italy

REDAKSİYON (REDACTION) Erman Aytaç

ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY

Başkan (President) Başkan Yardımcısı (Vice President) Genel Sekreter (Secretary General) Sayman (Treasurer) Yönetim Kurulu Üyeleri (Members)

Recep Güloğlu Kaya Sarıbeyoğlu M. Mahir Özmen Ali Fuat Kaan Gök Hakan Teoman Yanar Gürhan Çelik Osman Şimşek

İLETİŞİM (CORRESPONDENCE)

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

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

ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ YAYIN ORGANI ISSUED BY THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY

Ulusal Travma ve Acil Cerrahi Derneği adına Sahibi (Owner) Yazı İşleri Müdürü (Editorial Director) Yayın Koordinatörü (Managing Editor) Amblem Yazışma adresi (Correspondence address)

Tel Faks (Fax)

Recep Güloğlu Recep Güloğlu 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

Abonelik: 2013 yılı abone bedeli (Ulusal Travma ve Acil Cerrahi Derneği’ne bağış olarak) 75.- YTL’dir. Hesap No: Türkiye İş Bankası, İstanbul Tıp Fakültesi Şubesi 1200 - 3141069 no’lu hesabına yatırılıp makbuz dernek adresine posta veya faks yolu ile iletilmelidir. Annual subscription rates: 75.- (USD) p-ISSN 1306-696x • e-ISSN 1307-7945 • Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır. (Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus and Turkish Medical Index) • Yayıncı (Publisher): KARE Yayıncılık (karepublishing) • Tasarım (Design): Ali Cangül • İngilizce Editörü (Linguistic Editor): Corinne Can • İstatistik (Statistician): Empiar • Online Dergi & Web (Online Manuscript & Web Management): LookUs • Baskı (Press): Yıldırım Matbaacılık • Basım tarihi (Press date): Haziran (June) 2013 • Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur. (This publication is printed on paper that meets the international standard ISO 9706: 1994).

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. 2001-2006 yılları arasındaki 5 yıllık dönemde SCI-E kapsamındaki dergilerdeki 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.

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. For the five-year term of 2001-2006, 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.

ULUSAL TRAVMA VE AC‹L CERRAH‹ DERG‹S‹ TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY C‹LT - VOL. 19

SAYI - NUMBER 4 TUMMUZ - JULY 2013

İçindekiler - Contents ix Editöryal - Editorial

Deneysel Çalışma - Experimental Study 285-293 Effects of low-dose methotrexate in spinal cord injury in rats

Düşük doz metotreksatın sıçanlarda omurilik yaralanmasına etkileri

Bakar B, Köse EA, Kupana Ayva Ş, Sarkarati B, Kasımcan MÖ, Kılınç K 294-298 The effects of lornoxicam on brain edema and blood brain barrier following diffuse traumatic brain injury in rats

Lornoksikamın sıçanlarda diffüz travmatik beyin hasarında beyin ödemi ve kan beyin bariyeri üzerine etkileri

Topçu İ, Gümüşer G, Bayram E, Aras F, Çetin İ, Temiz C, Çivi M 299-304 Genotoxicity of fixation devices analyzed by the frequencies of sister chromatid exchange

Fiksasyon araçlarının genotoksisitesinin kardeş kromatit değişim sıklığıyla analizi

Aydil BA, Koçak Berberoğlu H, Öztürk S, Cefle K, Palandüz Ş, Erkal H 305-312 Karın içi adezyon önleyici %4’lük ikodekstrin solüsyonunun gastrointestinal sistem anastomozları üzerine etkisi

Effects of abdominal adhesion-preventing 4% icodextrin solution on healing of bowel anastomoses

Koç O, Dağ A, Öcal AK, Dirlik MM, Çömelekoğlu Ü, Gümüş LT, Serinsöz E, Kanık EA, Akça H 313-319 Effects of combined and individual use of N-methyl-D aspartate receptor antagonist magnesium sulphate and caspase-9 inhibitor z-LEDH-fmk in experimental spinal cord injury

Sıçanlarda oluşturulan deneysel omurilik yaralanmasında N-metil D-aspartat reseptör antagonisti olan magnezyum sülfat ve kaspaz-9 inhibitörü olan z-LEDH-fmk’nın tek başına ve kombine kullanımlarındaki etkinliklerinin karşılaştırılması

Sencer A, Aydoseli A, Aras Y, Akçakaya MO, Gömleksiz C, Can H, Canbolat A

Klinik Çalışma - Original Articles 320-326 Analysis of appropriate tetanus prophylaxis in an Emergency Department

Acil serviste yapılan tetanoz proflaksisi uygunluğunun analizi

Şimşek G, Armağan E, Köksal Ö, Heper Y, Eraybar Pozam S, Durak VA 327-332 Acil serviste “Genişletilmiş Acil Travma Ultrasonografisi” uygulamalarının klinik karar üzerine etkisi

Impact of the practice of “Extended Focused Assessment with Sonography for Trauma” (e-FAST) on clinical decision in the emergency department

Uz İ, Yürüktümen A, Boydak B, Bayraktaroğlu S, Özçete E, Çevrim Ö, Ersel M, Kıyan S 333-336 Treatment of acute scrotum in children: 5 years’ experience

Çocukluk çağı akut skrotum olgularında tedavi yaklaşımı: 5 yıllık deneyim

Erikci VS, Hoşgör M, Aksoy N, Okur Ö, Yıldız M, Dursun A, Demircan Y, Örnek Y, Genişol İ 337-342 Non-operative treatment approach for blunt splenic injury: is grade the unique criterion?

Künt dalak yaralanmalarında ameliyatsız tedavi: Derecelendirme tek kriter midir?

Koca B, Topgül K, Yürüker SS, Çınar H, Kuru B Cilt - Vol. 19 Sayı - No. 4

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SAYI - NUMBER 4 TEMMUZ - JULY 2013

İçindekiler - Contents 343-347 Thoracic aortic aneurysms after blunt trauma

Künt travmalardan sonra oluşan torasik aort anevrizmaları

Taşoğlu İ, Sert DE, Lafçı G, Genç B, Kavasoğlu K, Ulus AT, Paç M 348-356 Fractures of the mandible: a 20-year retrospective analysis of 753 patients

Mandibula kırıkları: 753 hastanın 20 yıllık geriye dönük değerlendirmesi

Eskitaşcıoğlu T, Özyazgan İ, Çoruh A, Günay GK, Yontar Y, Altıparmak M 357-362 Demographic and etiologic characteristics of children with traumatic serious hyphema

Çocuklarda travmatik ciddi hifemalarda demografik ve etyolojik özellikler

Türkcü FM, Yüksel H, Şahin A, Cingü K, Arı Ş, Çınar Y, Şahin M, Yıldırım A, Çaça İ

Olgu Sunumu - Case Reports 363-365 Künt travmanın nadir komplikasyonu; Çocuk olguda diyafram-perikart rüptürü ve kardiyak herniasyon

A rare complication of blunt trauma; diaphragm-pericardium rupture and cardiac herniation in a child case

Arslan E, Işık AF, Şanlı M, Uluşan A, Elbeyli L 366-370 Traumatic renal artery occlusion in the pediatric age group: a case and review of the literature

Pediatrik yaş grubunda travmatik renal arter oklüzyonu: Bir olgu ve literatürün gözden geçirilmesi

Garge S, Kanojia R, Rao K 371-374 Gebe bir kadında av tüfeği yaralanması sonucu fetüs beyin dokusunda rezidüel saçma tanesi: Bir olgu sunumu

Residual pellet in fetal brain tissue following a gunshot injury to a pregnant woman: a case report

Gündoğmuş ÜN, Akkaya H, Karbeyaz K, Keskin A 375-379 Bouveret syndrome: evaluation with multidetector computed tomography and contrast-enhanced magnetic resonance cholangiopancreatography

Bouveret sendromu: Çok kesitli bilgisayarlı tomografi ve kontrastlı manyetik rezonans kolanjiyografi bulguları

Algın O, Özmen E, Metin MR, Ersoy PE, Karaoğlanoğlu M 380-382 De Garengeot’s hernia: a case of acute appendicitis in a femoral hernia sac

De Garengeot fıtığı: Femoral fıtık kesesi içinde bir akut apandisit olgusu

Şen Tanrıkulu C, Tanrıkulu Y, Akkapulu N 383-384 Severe burn on 81% of body surface after sun tanning

Güneşte bronzlaşma sonrası vücut yüzeyinin %81’inde ağır yanık

Sforza M, Andjelkov K, Zaccheddu R 385-386 An extremely rare appendiceal anomaly: horseshoe appendicitis

Apendiksin çok nadir bir anomalisi: At nalı apandisit

Oruç C, Işık Ö, Üreyen O, Kahyaoğlu OS, Köseoğlu A

viii

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4)

EDİTÖRYAL

Buruk bir yazı...

Değerli Meslektaşlarım, Sevgili Meslektaşımız Dr. Ersin Arslan’ı meslek şehidi olarak kaybetmenin derin üzüntüsü tüm tıp camiasında hala tazeliğini korumaktadır. Bu nedenle geçtiğimiz Nisan ayında Antalya’da düzenlemiş olduğumuz 9. Ulusal Travma ve Acil Cerrahi Kongresi’nde bir oturumu Dr. Ersin Arslan’ın adına ithaf etmiştik.

Dr. Ersin Arslan

Sağlık gibi insanlara en çok hizmet eden bir alanda, gecesini gündüzüne katarak çok yoğun çalışan ve fedakarca emek veren meslektaşlarımıza yapılan ve maalesef son yıllarda giderek artan bu saldırıları şiddetle kınıyoruz. Arkadaşlarımızı kaybettiğimiz insanlık dışı bu saldırılar, tıp hizmeti verme çabasının da önünü kesmeye başlamıştır.

Dergimizin bu sayısında Dr. Ersin Arslan’ın acı kaybından önce kaleme aldığı bir çalışması yer almaktadır. Bu yazı, değerli meslektaşımızın bilim dünyasına vefatından önce verdiği son bir bilimsel katkı olarak literatürdeki özel yerini alacaktır. Dr. Ersin Arslan’ın şu anda aramızda olmasını ve dergide yazısının basıldığını görmesini çok isterdik. Bizi bir nebze de olsa avutan çalışmasını gelecek kuşaklara aktarmada, Ulusal Travma ve Acil Cerrahi Dergisi olarak rol almış olmak. Bu çok anlamlı çalışmanın dergimizde yayınlanmasını bir onur olarak kabul ediyoruz.

Günümüzde ve gelecekte toplumumuzun bu acıları tekrar yaşamaması dileğiyle.

Saygılarımızla, Editörler Kurulu

Cilt - Vol. 19 Sayı - No. 4

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Ulus Travma Acil Cerrahi Derg 2013;19 (4):285-293

Experimental Study

Deneysel Çalışma doi: 10.5505/tjtes.2013.65475

Effects of low-dose methotrexate in spinal cord injury in rats Düşük doz metotreksatın sıçanlarda omurilik yaralanmasına etkileri Bülent BAKAR,1 Emine Arzu KÖSE,2 Şebnem KUPANA AYVA,3 Bahram SARKARATİ,4 Mustafa Ömür KASIMCAN,1 Kamer KILINÇ4

BACKGROUND

AMAÇ

This study was designed to evaluate the possible protective effects of low-dose methotrexate in the spinal cord injury (SCI) in rats.

Bu çalışma, düşük doz metotreksatın sıçanlarda oluşturulan omurilik yaralanması üzerindeki olası koruyucu etkilerini incelemek amacıyla yapıldı.

METHODS

GEREÇ VE YÖNTEM

Thirty-seven Wistar albino rats were used in the present study. Except for the animals of the Sham group, all animals were divided into two main groups, which were used in acute and subacute stage investigations. Then, thoracal laminectomy was performed, and except for the Sham group, SCI was induced using a temporary aneurysm clip.

After clip compression, the experimental material (methotrexate or methylprednisolone) was administered intraperitoneally, except in the Sham and Control groups. Then, the spinal cords were removed to evaluate the SCI histopathologically and biochemically at the scheduled date.

Otuz yedi adet Wistar albino sıçan üzerinde torakal laminektomi uygulandı ve sham grubu hariç tüm hayvanlarda geçici anevrizma klibi kullanılarak omurilik travması oluşturuldu. Akut ve subakut dönemde travmanın etkilerini incelemek amacıyla sham grubundaki hayvanlar dışındaki diğer hayvanlar iki ana gruba ayrıldı. Travma sonrası sham ve kontrol grupları hariç tüm hayvanlara ilgili deneysel ilaç (metotreksat veya metilprednisolon) periton içine verildi.

Hayvanların omurilikleri travmanın histolojik ve biyokimyasal etkilerini incelemek amacıyla çıkarıldı.

RESULTS

Neither experimental material was shown to reduce the histopathological grade in either stage of SCI. Low-dose methotrexate was shown to decrease lipid peroxidation levels only in the subacute stage of SCI. However, methylprednisolone and low-dose methotrexate could not decrease or block myeloperoxidase enzyme activation in either stage of SCI.

Her iki deneysel materyalin de omurilik travmasının herhangi bir evresinde histopatalojik düzeyde belirgin düzeltici etkisinin olmadığı gözlendi. Travmanın gözlenen subakut evresinde metotreksatın lipit peroksidasyon düzeyini azaltmada metilprednisolona göre belirgin üstünlüğe sahip olduğu saptandı. Ancak, akut ve subakut dönemlerde her iki ajanın da miyeloperoksidasyon düzeyleri üzerinde etkili olmadığı saptandı.

CONCLUSION

SONUÇ

Low-dose methotrexate was effective in reducing the lipid peroxidation levels in the subacute stage of SCI, although histopathological evaluation results and myeloperoxidase levels of all groups did not support this finding at either stage.

Düşük doz metotreksatın sıçanlarda oluşturulan omurilik yaralanmasının subakut döneminde gelişen lipit peroksidasyon düzeyleri üzerinde azaltıcı etkisi olduğu ancak miyeloperoksidasyon aktiviteleri ve histopatolojik evre bulguları üzerinde etkili olmadığı saptanmıştır.

Key Words: Low-dose methotrexate; methylprednisolone; spinal cord injury.

Anahtar Sözcükler: Düşük doz metotreksat; metilprednisolon; omurilik yaralanması.

Departments of 1Neurosurgery, 2Anaestesiology and Reanimation, Kirikkale University Faculty of Medicine, Kirikkale; 3 Department of Pathology, Baskent University Faculty of Medicine, Ankara; 4 Department of Biochemistry, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Kırıkkale Üniversitesi Tıp Fakültesi, 1Nöroşirürji Anabilim Dalı, 2 Anesteziyoloji ve Reanimasyon Anabilim Dalı, Kırıkkale; 3 Başkent Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Ankara; 4 Hacettepe Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Ankara.

BULGULAR

Correspondence (İletişim): Bülent Bakar, M.D. Kırıkkale Ünniversitesi Tıp Fakültesi, Fabrikalar Mah., Sağlık Cad. Sağlık Sok., 71100 Kırıkkale, Turkey.

Tel: +90 - 318 - 225 24 85 e-mail (e-posta): bulentbanrs@yahoo.com

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Many reports in the literature have explained that some biochemical and inflammatory reactions, called secondary cord damage, develop due to the primary effects of spinal cord injury (SCI) and promote the occurrence of edema and hemorrhage during the acute stage. This response includes vascular permeability, excessive release of glutamate and aspartate, intracellular calcium overload, activation of the arachidonic acid cascade, induction of lipid peroxidation (LPO), and activation of resident glial cells. These events precede infiltration by large numbers of inflammatory cells such as neutrophils and macrophages, which can destroy the neurons and sheath of axons by releasing excessive amount of cytokines, cytotoxic substances (such as superoxide anion, chloride anion, hydroxyl radicals), and tumor necrosis factor-alpha (TNF-α).[1,2] Additionally, microglia can also produce superoxide and nitric oxide when they are exposed to oxidative stress. Today, it has been accepted that the critical step for the acute treatment of SCI is to reduce these cytokines by blocking the infiltration of these inflammatory cells into the injured spinal cord, as it will reduce secondary cord damage.[1] Recently, low-dose methotrexate (MTX) has become the mainstay in the treatment of some inflammatory diseases such as rheumatoid arthritis.[3,4] Chronstein et al.[3] showed that low-dose MTX can inhibit both proliferation of lymphocytes in an inflammatory exudate and reduce the destructive capacity of the leukocytes that do arrive at the inflammation site.

Although its exact mechanism of action has not been clarified yet, low-dose MTX promotes extracellular adenosine accumulation at the inflammation sites. Adenosine, which interacts with its receptors (adenosine A2 receptor) in stimulated inflammatory cells, inhibits some cytokines such as interleukin (IL)-1, IL-4, IL13, interferon (IFN)-gamma, leukotrienes released by neutrophils (but not macrophages), and granulocyte macrophage colony-stimulating factor. Adenosine also inhibits the superoxide, nitric oxide and TNF-α released by monocytes and macrophages.[5] Additionally, adenosine has cytoprotective effects resulting from inhibition of the toxic oxygen metabolites that are generated from the adhesion of stimulated neutrophils to the endothelium.[3,6] Based on all these results, this preliminary study was designed to investigate the possible neuroprotective effects of low-dose MTX in the secondary damage of SCI in rats.

MATERIALS AND METHODS Materials This experimental study was performed in accordance with the guidelines for the use of laboratory animal subjects in a research setting by the Ethical Com286

mittee of Kırıkkale University (Number: 11/204).

Methotrexate (MTX; Methotrexate DBL, Hospira Australia PYY Ltd., Mulgrave, Victoria, Australia) and methylprednisolone (MP; Depo-Medrol®, Pharmacia & Upjohn Company, Kalamazoo, USA) were used in this study. The density of Methotrexate DBL is 25 mg/ml, and the intraperitoneal LD50 of Methotrexate DBL is 6 mg/kg in rats. The density of DepoMedrol® is 40 mg/ml, and the intraperitoneal LD50 of Depo-Medrol® is 1 g/kg in rats.

Thirty-seven Wistar albino rats weighing 250-350 g were used in this study. Except for the animals of the Sham group (n=5), all animals were divided into two main groups randomly, which were used in the acute (72 hours after SCI) and subacute (5 days after SCI) stage investigations of SCI. Then, each main group was also divided into three subgroups as described below. Neither clip compression nor experimental material administration was performed to the animals of the Sham group.

The acute stage groups were divided into three subgroups randomly as follows: - Control-A group (no chemical material was infused; n=5) - MP-A group (methylprednisolone was infused intraperitoneally; n=5) - MTX-A group (low-dose methotrexate was infused intraperitoneally; n=7) The subacute stage groups were also divided into three subgroups randomly as follows: - Control-C group (no chemical material was infused; n=5) - MP-C group (methylprednisolone was infused intraperitoneally; n=5) - MTX-C group (low-dose methotrexate was infused intraperitoneally; n=5) Anesthesia was performed with intramuscular administration of ketamine HCl (Ketalar®; Pfizer Inc, USA) and xylazine HCl (Rompun® 2%; Bayer HealthCare AG, Germany).

Methods The spinal cord contusion was performed using a clip compression technique described by Rivlin and Tator.[7] All animals were sedated with intramuscular 40 mg/kg ketamine HCl and 5 mg/kg xylazine HCl on spontaneous respiration at room temperature. A dorsal laminectomy at thoracal 9-10 level was performed to all animals, and the dura mater was left intact. The spinal cord was exposed, and except for the Sham group, SCI was induced using a temporary Temmuz - July 2013

Effects of low-dose methotrexate in spinal cord injury in rats

(a)

(b)

(c)

(d)

Fig. 1. (a) A dorsal laminectomy at thoracal 9-10 level was performed, and (b, c) traumatic SCI was induced by using a temporary aneurysm clip applied for 60 seconds (d) that resulted in hind limb locomotor deficit.

(Color figures can be viewed in the online issue, which is available at www.tjtes.org).

aneurysm clip (Mizuho® Aneurysm Clip, Mizuho, Japan) for 60 seconds (Fig. 1). Four hours after the clip compression, except rats of the Sham, Control-A and Control-C groups, the experimental material (0.05 mg/ kg MTX or 30 mg/kg MP) was slowly administered (within 5 seconds) through the intraperitoneal route using a 22G needle. After this procedure, all rats were removed from sedation spontaneously under the blanket. Hind limb locomotor deficit resulting from SCI was observed in all rats except the Sham group animals (Fig. 1). Seventy-two hours later, the animals of the Sham, Control-A, MP-A, and MTX-A groups and 5 days later the animals of the Control-C, MP-C, and MTX-C groups were re-sedated with intramuscular 40

mg/kg ketamine HCl and 5 mg/kg xylazine HCl. After sedation, rats were sacrificed using cardiac air embolization. Then, the first dorsal incision of the animals was re-opened, and the spinal cords were removed totally from the T8 to the conus medullaris level. The sample tissues were immediately harvested for future biochemical and histopathological examinations, and divided into two parts. The proximal part of the spinal cord, to which clip compression was applied, was stored in 10% buffered formaldehyde solution at room temperature for histopathological examination. The remaining distal part of the spinal cord was stored at -30°C in dry air for biochemical examination.

Specimen analysis For histopathological examination, all tissue samples were fixed in 10% buffered formaldehyde and processed according to routine light microscopic tissue processing technique. Serial sections of 5 µm stained with hematoxylin-eosin were examined and photographed with a light microscope (Leica® Microsystems, Wetzlar GmbH). Each section was evaluated by an experienced pathologist blinded to the groups and test materials. For histopathological evaluation of the SCI, a grading system described by Black et al.[8] was applied to all specimens as follows (Fig. 2): - grade 0: no destruction in the spinal cord tissue histopathologically.

- grade I: mild neural tissue destruction and polymorphonuclear cell infiltration without neuronal cell loss; the posterior column of the spinal cord was affected.

- grade II: moderate neural tissue destruction and

Grade 0

Grade 0

Grade 1

Grade 1

Grade 2

Grade 2

Grade 3

Grade 3

Fig. 2. Histopathological grades involved Grade 0: no neural tissue destruction; Grade I: mild neural tissue destruction and polymorphonuclear cell infiltration without neuronal cell loss - the posterior column of the spinal cord was affected; Grade II: moderate neural tissue destruction and macrophage and/or histiocyte infiltration with white matter loss and central cavitation; and Grade III: severe neural tissue destruction with white and gray matter cystic necrosis and gliosis (hematoxylineosin, original magnification x100, and x400). (Color figure can be viewed in the online issue, which is available at www.tjtes.org).

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Table 1. Descriptive table of the histopathological grades

Histopathological grades

Groups Sham Control-A MP-A MTX-A Control-C MP-C MTX-C

Median value

Grade 0

Grade 1

Grade 2

Grade 3

4 – – – – – –

1 – – – – 1 –

– 4 2 6 3 4 4

– 1 3 1 2 – 1

0 2 3 2 2 2 2

MP: Methylprednisolone; MTX: Methotrexate.

macrophage and/or histiocyte infiltration with white matter loss and central cavitation.

- grade III: severe neural tissue destruction with white and gray matter cystic necrosis and gliosis.[8] Biochemical determinations were carried out by two biochemists blinded to the animal groups and test materials. Frozen tissue samples were weighed and homogenized in 1:10 (w:v) potassium phosphate buffer (50 mM, pH: 7.4) using a dounce homogenizer. Thiobarbituric acid reactive substances (TBARS) were measured as an index of LPO by the method of Mihara et al.[9,10] Tissue levels of lipid peroxides (as TBARS) were calculated as nanomole per gram wet tissue.

Tissue-associated myeloperoxidation (MPO) activity was measured by the modified method of Suzuki et al.[11,12] Tissue homogenate (0.5 ml) was centrifuged at 10.000xg for 5 minutes (min), and the pellet was resuspended in equal volume (0.5 ml) of 50 mM phosphate buffer (pH=6.0) containing 0.5% hexadecyltrimethyl ammonium bromide (HETAB) and 5 mM EDTA. The resulting suspension was centrifuged at 5.000xg for 2 min and the supernatant was used for the activity measurement. The MPO activity was measured in a final 7

Statistical analysis Histopathological grades that were not normally distributed and the variation that was not homogeneous between all groups were statistically analyzed by the chi-square test. To determine the statistical differences between the groups (post hoc evaluation), the chisquare test was performed to all grade results. P values lower than 0.05 were considered to be significant.

Tissue LPO and MPO levels were normally distributed and the variation was homogeneous between all 5

Grade 0 1 2 3

6

4 3 2

(a)

3 2 1

1 0

Grade 0 1 2 3

4 Count of cases

5 Count of cases

volume of 1 ml containing 80 mM phosphate buffer (pH=5.4), 0.5% HETAB, 1.6 mM synthetic substrate tetramethylbenzidine (TMB) initially dissolved in dimethylformamide, 2 mM H2O2, and the sample. The reaction was started at 37 °C with the addition of H2O2.

The initial rate of MPO-catalyzed TMB oxidation was followed by recording the increase of absorbance at 655 nm (Shimadzu® UV-120-02 spectrophotometry).

The MPO activity was expressed as the amount of the enzyme producing one absorbance change per minute under assay conditions. Tissue-associated MPO activity was calculated as units per gram of wet tissue.

Sham

Control-A MP-A Groups

MTX-A

0

(b)

Sham

Control-C MP-C Groups

MTX-C

Fig. 3. The variation of the histopathological grades in (a) acute and (b) subacute stages of SCI (MP: Methylprednisolone; MTX: Methotrexate).

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Effects of low-dose methotrexate in spinal cord injury in rats

groups. Therefore, they were statistically analyzed by the one-way analysis of variance (one-way ANOVA) test. Furthermore, to determine the statistical differences between the groups, post hoc evaluation (oneway ANOVA-Tukey multiple comparisons test and Bonferroni multiple comparisons test) was performed to all biochemical results. P values lower than 0.0083 were considered to be significant.[13]

RESULTS Light Microscopy Four rats of the Sham group had grade 0, and 1 rat had grade I degeneration.

In the acute stage, 4 rats of the Control-A group had grade II, and 1 rat had grade III degeneration.

Two rats of the MP-A group had grade II and 3 rats had grade III degeneration. In the MTX-A group, 6 rats had grade II, and 1 rat had grade III degeneration (Table 1, Fig. 3). Except for 3 animals of the ControlA group, which had mild acute inflammatory reaction, no inflammatory reaction was observed in the remaining groups.

In the subacute stage, 3 rats of the Control-C group had grade II, and 2 rats had grade III degeneration.

Three of them had mild chronic inflammatory reaction (glial histiocyte infiltration). One rat of the MP-C group showed grade I, and the other 4 rats showed grade II degeneration. Three of them had moderate inflammatory reaction developed due to neutrophils.

In the MTX-C group, 4 rats had grade II and 1 rat had grade III degeneration (Table 1, Fig. 3). In 4 of them, severe inflammatory reaction developed due to mixed type inflammatory cell infiltration (macrophages and histiocytes).

The variation of the median values of the histopathological grades was statistically significant when the acute and subacute stages of all groups were compared using the chi-square test (X2= 29.270, p<0.001) (Table 2). The post hoc evaluation results obtained from the chi-square test showed that there were significant differences between the Sham/Control-A (degrees of freedom [df]=3, p=0.019), Sham/ControlC (df=3, p=0.019), Sham/MP-A (df=3, p=0.019), Sham/MP-C (df=3, p=0.018), Sham/MTX-A (df=3, p=0.007), and Sham/MTX-C groups (df=3, p=0.019) (Table 3, Fig. 3).

Biochemical analysis The evaluation of LPO levels The variation of the mean values of the LPO levels was statistically significant (p=0.001; F=5.119) using the one-way ANOVA test (Tables 4, 5). The post hoc evaluation results of the LPO levels obtained using the one-way ANOVA-Tukey multiple comparisons test Cilt - Vol. 19 Say覺 - No. 4

Table 2. This table demonstrates that there was a statistically significant difference between all groups described in the text when comparing their histopathological grades

Histopathological grade

Chi-square

df

p

29.270

3

<0.001

chi-square test, p<0.05. df: Degrees of freedom.

Table 3. The post hoc evaluation shows that neither experimental material could reduce the histopathological grade in either stage of spinal cord injury Groups

df

p

Sham/Control-A Sham/MP-A Sham/MTX-A Control-A/MP-A Control-A/MTX-A MP-A/MTX-A Sham/Control-C Sham/MP-C Sham/MTX-C Control-C/MP-C Control-C/MTX-C MP-C/MTX-C

3 3 3 1 1 1 3 2 3 1 1 1

0.019* 0.019* 0.007* 0.262 0.682 0.152 0.019* 0.018* 0.019* 0.095 0.500 0.180

chi-square test, p<0.05. MP: Methylprednisolone; MTX: Methotrexate; df: Degrees of freedom.

demonstrated that there were significant differences between the Control-C/MTX-C groups (p=0.007) (Table 6, Fig. 4).

The evaluation of MPO levels The variation of the mean values of the MPO levels was statistically significant obtained using the one-way ANOVA test (F=7.766, p<0.001) (Tables 4, 5). The post hoc evaluation results of the MPO levels showed that there were significant differences between Sham/ Control-A (p=0.001), Sham/Control-C (p=0.005), and Sham/MP-C groups (p<0.001) (Table 7, Fig. 5).

DISCUSSION Evaluation of the histopathological results Acute SCI is followed by progressive secondary procedures of tissue destruction arising from the inflammatory response. This inflammatory response is biphasic. The first phase involves lysosomal degradation and free radical formation, which have a role in chemotaxis of the neutrophils and tissue macrophages.

Neutrophil infiltration into the injured spinal cord tissue occurs in approximately 6 hours. It peaks in 24 to 48 hours and may persist during the first week.[14,15] The 289

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Table 4. Descriptive table of the mean lipid peroxidation and myeloperoxidation levels Groups

Variable

Minimum

Maximum

Mean

SD

LPO MPO LPO MPO LPO MPO LPO MPO LPO MPO LPO MPO LPO MPO

37.23 0.00 59.65 16.39 44.42 5.06 37.23 0.00 64.73 14.52 38.08 5.61 39.77 8.58

56.70 4.07 79.96 18.59 68.11 18.26 68.11 16.61 71.92 16.17 76.58 34.98 52.04 17.27

48.32 1.43 68.54 17.53 56.10 10.03 51.37 9.37 68.28 15.16 55.42 22.11 45.44 12.89

7.46 1.57 7.46 0.84 9.22 5.80 11.68 6.14 2.625 0.64 13.76 10.57 4.90 3.10

Sham

Control-A

MP-A

MTX-A

Control-C

MP-C

MTX-C

LPO: Lipid peroxidation; MP: Methylprednisolone; MPO: Myeloperoxidation; MTX: Methotrexate; SD: Standard deviation.

second phase includes damaging of the neural tissue by macrophages, microglia and histiocytes.[16] Clinical studies have suggested that pharmacologic therapies may be effective in minimizing the observed outcomes after SCI. Although many pharmacological agents have been described as a potential effective agent to improve the secondary cord damage caused by SCI, steroids are still accepted worldwide as a single option for urgent treatment of SCI. Steroids have antioxidant, anti-inflammatory, and cell membrane stabilizing properties, and may be beneficial in a time- and dose-dependent manner. They have also anti-edema activities.[17] In the present study, almost all groups had grade II degeneration except those of the Sham and MP-A

groups. These results showed that neither experimental material could reduce the histopathological grades in either stage of SCI. Further, it could be presumed that statistical differences were derived from the Sham group values. In the acute stage, mild to moderate neuronal destruction with demyelination and cavity formation was found in all groups except the Sham group. It can be suggested that neither low-dose MTX nor MP could decrease the neural tissue destruction and necrosis in the acute or subacute stages of SCI in rats.

The histopathological observations showed no inflammatory reaction in any specimens of groups in the acute stage of SCI except the Control-A group. This finding may be explained by the potent anti-inflamma-

90.00

40.00

30.00

Myeloperoxidation level

Lipid peroxidation level

80.00 70.00 60.00 50.00 40.00 30.00 N=

5 Control-A

5 Control-C

5 Sham

5 MP-A

5 MP-C

7 MTX-A

5 MTX-C

Groups

Fig. 4. The mean values of the lipid peroxidation levels in acute and subacute stages of SCI. Each error bar shows minimum and maximum lipid peroxidation levels (MP: Methylprednisolon; MTX: Methotrexate).

290

20.00

10.00

0.00

-10.00 N=

5 Control-A

5 Control-C

5 Sham

5 MP-A

5 MP-C

7 MTX-A

5 MTX-C

Groups

Fig. 5. The mean values of the myeloperoxidation levels in acute and subacute stages of SCI. Each error bar shows minimum and maximum myeloperoxidation levels (MP: Methylprednisolone; MTX: Methotrexate).

Temmuz - July 2013

Effects of low-dose methotrexate in spinal cord injury in rats

Table 5. Variations in the mean lipid peroxidation and myeloperoxidation levels were statistically significant between all groups

Lipid peroxidation Myeloperoxidation

F

p

5.119 7.766

0.001 <0.001

One-way ANOVA test, p<0.05. F: F test.

tory effect of MP and low-dose MTX, and based on this result, it may be predicted that those experimental materials would cause a reduction in the histopathological grade results. However, the median values of the histopathological grades of the MP-A and MTXA groups were not statistically different from the val-

ues of the Control-A group. It can thus be suggested that neither experimental material could decrease or block the inflammatory reaction in the acute stage of SCI in rats. Moreover, moderate inflammatory reaction caused by neutrophils was observed in specimens of the MP-C group, and severe inflammatory reaction developed due to macrophages and histiocytes was observed in the specimens of the MTX-C group. This may mean that MP could not block the neutrophil infiltration into the damaged tissue, and low-dose MTX may enhance the macrophage or histiocyte infiltration into the injured neural tissue in the subacute stage of SCI. Although it could be predicted that these inflammatory reactions would increase the histopathological grades in the MTX-C and MP-C groups, the median values did not support this (Table 1). Even though we

Table 6. Low-dose MTX could decrease lipid peroxidation levels in both stages of spinal cord injury in rats (I) Group

(J) Group

Mean Difference (I-J)

Standard error

p

Sham

Control-A

MP-A Sham

Control-C

MP-C

Control-A MP-A MTX-A MP-A MTX-A MTX-A Control-C MP-C MTX-C MP-C MTX-C MTX-C

-20.22 -7.78 -3.05 12.44 17.16 4.73 -19.97 -7.11 2.88 12.86 22.85 9.99

5.76 5.76 5.33 5.76 5.33 5.33 5.76 5.76 5.76 5.76 5.76 5.76

0.022 0.822 0.997 0.346 0.043 0.972 0.024 0.875 0.999 0.308 0.007 0.599

One-way ANOVA-Tukey multiple comparison test and Bonferroni multiple comparison test t, p<0.0083.

MP: Methylprednisolone; MTX: Methotrexate.

Table 7. Low-dose MTX could reduce myeloperoxidation levels in the subacute stage of spinal cord injury in rats (I) Group

(J) Group

Mean Difference (I-J)

Standard error

p

Sham

Control-A

MP-A Sham

Control-C

MP-C

Control-A MP-A MTX-A MP-A MTX-A MTX-A Control-C MP-C MTX-C MP-C MTX-C MTX-C

-16.10 -8.60 -7.94 7.50 8.17 0.67 -13.73 -20.6 -11.46 -6.95 2.27 9.22

3.39 3.39 3.14 3.39 3.14 3.14 3.39 3.39 3.39 3.39 3.39 3.39

0.001 0.181 0.184 0.318 0.160 1.000 0.005 <0.001 0.029 0.405 0.993 0.127

One-way ANOVA-Tukey multiple comparison test and Bonferroni multiple comparison test t, p<0.0083 MP: Methylprednisolone; MTX: Methotrexate.

Cilt - Vol. 19 Say覺 - No. 4

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could not demonstrate in the current study the efficacy of these materials in the chronic stage of SCI, it can be said that both experimental materials were inefficient in blocking the inflammatory cell infiltration in the subacute stage of SCI in rats.

Evaluation of the biochemical results Evaluation of the LPO levels Neutrophils and other phagocytes are major sources of free radicals in the extracellular space in damaged tissue.[1] Additionally, ischemia induced by SCI challenges tissue energy demands and active ion channel functions, and then it may force the neurons to switch from aerobic to anaerobic metabolism. This oxidative stress following SCI may also produce free radicals, which could initiate the LPO activity in the damaged neural tissue.[18] Biochemical evaluation results of the present study demonstrated that neither low-dose MTX nor MP could decrease the LPO levels of the injured neural tissue in the acute stage of SCI. On the other hand, low-dose MTX could decrease the LPO levels to a much greater extent than all other groups, only in the subacute stage. This result may mean that low-dose MTX may be beneficial in reducing the LPO levels and decreasing the free radicals and their destructive effects in the subacute stage of SCI in rats. On the other hand, there was no statistically significant difference between the MTX and MP groups in the subacute stage. It may mean that MP can reduce the LPO levels as much as low-dose MTX. Nevertheless, there was no difference between the Control-C and MP-C groups. Thus, it can be said that low-dose MTX could be much more effective than MP in reducing LPO levels in the subacute stage of SCI. Evaluation of the MPO levels When the neutrophils and other phagocytes reach the injured spinal cord tissue, they produce hypochlorite, a strong oxidant synthesized by the enzyme MPO. [1] MPO is a specific enzyme in the granules of the neutrophils and other phagocytes. MPO activity is correlated with the absolute number of neutrophils and their activations.[14,15] Thus, MPO activity begins to increase gradually during the first 72 hours after SCI, and then returns to uninjured levels in approximately one week after SCI.[1] In the present study, the mean MPO values of the Control, MP and MTX groups demonstrated that neither low-dose MTX nor MP could decrease the MPO activity in either stage of SCI. This may mean that MP and low-dose MTX could not decrease or block the MPO enzyme activity originated from the lysosomes of the inflammatory cells. Histopathological evaluation results also support these findings.

292

Study limitations This study has some pitfalls. First, this study does not contain the behavioral test results or the histopathological and biochemical evaluation results occurring in the long run. As we considered at the onset of the study to investigate the effects of low-dose MTX and MP exclusively in the early stages of SCI in rats, we did not obtain the evaluation results mentioned above because of the short time period. Second, we agree that this study does not contain more specific histopathological analysis for other mechanisms of secondary SCI. Thus, this study should be supported with immunohistochemical and electron microscopic findings that can show ultrastructural details of the inflammatory response, neuronal necrosis and edema in the acute and/or chronic stages of SCI. However, those techniques could not be supported due to inadequacies in our laboratory and equipment. This study should also be supported by using more specific biochemical analyses for other detailed inflammatory pathways of SCI (such as apoptotic pathways, glutathione level, nitrite/nitrate level, and xanthine oxidase activity level measurements). Unfortunately, those tests could not be performed because of some financial and technical restraints. Third, we should evaluate the effects of intrathecal MTX in secondary SCI. However, studies have pointed out that intrathecal MTX may have neurotoxic effects on the spinal cord tissue through development of axonal swelling and loss, demyelination and astrocytosis.[19-22] We thus did not constitute the groups to evaluate the effectiveness of MTX infused via the intrathecal route. Fourth, in this study, we did not constitute a group to examine the combined effects of low-dose MTX and MP on the secondary mechanisms of SCI. In conclusion, this preliminary study demonstrated that: 1) Neither low-dose MTX nor MP administration could alter the onset or degree of necrosis in the SCI zone in rats.

2) Low-dose MTX could be much more effective than MP in reducing the LPO levels in the subacute stage of SCI in rats.

3) Neither low-dose MTX nor MP could decrease the MPO levels at either stage of SCI. In conclusion, low-dose MTX was more effective than MP in the prevention of LPO activation only in the subacute stage of SCI, even though histopathological evaluation results and MPO values of the groups did not support this finding in either stage of SCI in rats.

Acknowledgement The authors express their gratitude to Mrs. ZerTemmuz - July 2013

Effects of low-dose methotrexate in spinal cord injury in rats

rin Nakip for editing the manuscript and to Mr. Erkan Kaya for his skilled assistance during the study.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Bao F, Chen Y, Dekaban GA, Weaver LC. Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats. J Neurochem 2004;88:1335-44.

2. Kaynar MY, Hanci M, Kafadar A, Gümüştaş K, Belce A, Ciplak N. The effect of duration of compression on lipid peroxidation after experimental spinal cord injury. Neurosurg Rev 1998;21:117-20.

3. Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993;92:2675-82.

4. Katchamart W, Trudeau J, Phumethum V, Bombardier C. Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 2009;68:1105-12.

5. Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002;4:266-73.

6. Montesinos MC, Takedachi M, Thompson LF, Wilder TF, Fernández P, Cronstein BN. The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5’-nucleotidase: findings in a study of ecto-5’-nucleotidase gene-deficient mice. Arthritis Rheum 2007;56:1440-5.

7. Rivlin AS, Tator CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 1978;10:38-43.

8. Black P, Markowitz RS, Cooper V, Mechanic A, Kushner H, Damjanov I, et al. Models of spinal cord injury: Part 1. Static load technique. Neurosurgery 1986;19:752-62.

9. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-8.

10. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.

11. Demirpençe E, Köksoy C, Kuzu A, Kılınç K. A spectropho-

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tometric assay for tissue-associated myeloperoxidase activity and its application to intestinal ischemia-reperfusion. Turk J Med Sci 1997;27:197-200.

12. Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T. Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 1983;132:345-52.

13. Nie NH, Hull CH, Jenkins JG. SPSS: statistical package for social science. New York: McGraw Hill Inc.; 1975.

14. Christie SD, Comeau B, Myers T, Sadi D, Purdy M, Mendez I. Duration of lipid peroxidation after acute spinal cord injury in rats and the effect of methylprednisolone. Neurosurg Focus 2008;25:E5.

15. Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods 1985;14:157-67.

16. Leskovar A, Moriarty LJ, Turek JJ, Schoenlein IA, Borgens RB. The macrophage in acute neural injury: changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems. J Exp Biol 2000;203:1783-95.

17. Merola A, O’Brien MF, Castro BA, Smith DA, Eule JM, Lowe TG, et al. Histologic characterization of acute spinal cord injury treated with intravenous methylprednisolone. J Orthop Trauma 2002;16:155-61.

18. Torres S, Salgado-Ceballos H, Torres JL, Orozco-Suarez S, Díaz-Ruíz A, Martínez A, et al. Early metabolic reactivation versus antioxidant therapy after a traumatic spinal cord injury in adult rats. Neuropathology 2010;30:36-43.

19. Gregorios JB, Gregorios AB, Mora J, Marcillo A, Fojaco RM, Green B. Morphologic alterations in rat brain following systemic and intraventricular methotrexate injection: light and electron microscopic studies. J Neuropathol Exp Neurol 1989;48:33-47.

20. Kwong YL, Yeung DY, Chan JC. Intrathecal chemotherapy for hematologic malignancies: drugs and toxicities. Ann Hematol 2009;88:193-201.

21. Mahoney DH Jr, Shuster JJ, Nitschke R, Lauer SJ, Steuber CP, Winick N, et al. Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy--a Pediatric Oncology Group study. J Clin Oncol 1998;16:1712-22.

22. Vezmar S, Becker A, Bode U, Jaehde U. Biochemical and clinical aspects of methotrexate neurotoxicity. Chemotherapy 2003;49:92-104.

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Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):294-298

Experimental Study

Deneysel Çalışma doi: 10.5505/tjtes.2013.32458

The effects of lornoxicam on brain edema and blood brain barrier following diffuse traumatic brain injury in rats Lornoksikamın sıçanlarda diffüz travmatik beyin hasarında beyin ödemi ve kan beyin bariyeri üzerine etkileri İsmet TOPÇU,1 Gül GÜMÜŞER,2 Eda BAYRAM,1 Feray ARAS,2 İsmail ÇETİN,1 Cüneyt TEMİZ,3 Melek ÇİVİ1

BACKGROUND

AMAÇ

In this experiment, the effects of lornoxicam on brain edema and the blood brain barrier (BBB) following diffuse traumatic brain injury (TBI) were studied.

Bu çalışmada diffüz travmatik beyin hasarı (TBH) sonrası, lornoksikamın kan beyin bariyeri (KBB) ve beyin ödemi üzerine etkileri araştırıldı.

METHODS

GEREÇ VE YÖNTEM

Twenty adult male Wistar albino rats were anesthetized, and experimental closed head trauma was induced by the Marmarou method. After head injury, the rats were randomly divided into two groups: Group I was the control group, to which 2 ml saline was administered intraperitoneally, and Group II was the lornoxicam group, to which 2 ml 1.3 mg kg-1 lornoxicam was administered intraperitoneally. Twentyfour hours after head trauma, 99 mTc pentetate (DTPA) was injected at a dose of 37 MBq, and posterior planar images of each rat were obtained using an Infinia gamma camera. After imaging of BBB permeability, brain tissues were dissected from the cranium. The brain water content (BWC) of each sample was calculated using the wet-dry method.

Yirmi erişkin erkek Wistar albino sıçana anestezi uygulaması sonrası Marmarou yöntemi ile deneysel kapalı kafa travması oluşturuldu. Kafa travması sonrası sıçanlar randomize olarak iki gruba ayrıldı: Grup I intraperitoneal yolla 2 mL salin uygulanan kontrol grubu ve Grup II intraperitoneal yolla 2 mL 1.3 mg kg-1 lornoksikam verilen lornoksikam grubu. Kafa travmasından 24 saat sonra 99 mTc pentetate (DTPA) 37 MBq dozda verildi ve her bir sıçanın posterior planar görüntüsü bir Infinia gama kamera kullanılarak elde edildi. KBB permebilitesinin görüntülenmesi sonrası beyin dokuları kranyumdan disseke edildi. Tüm örneklerin beyin su içeriği (BSI) ıslak-kuru metodu ile hesaplandı.

RESULTS

BULGULAR

The lesion/background (L/b) ratio of Group I was 3.76±0.46 and 3.02±0.66 for early (5th min) and late (60th min) imaging, respectively. In Group II, the L/b ratios were 3.52±0.96 and 2.63±0.63 for early and late imaging, respectively (p>0.05). BWC was 79.6±2.5% and 77.5±1.1% for Groups I and II, respectively (p<0.05).

Grup I lesion/background (L/b) oranları erken dönem (5. dk) 3,76±0,46 ve geç dönem (60. dk) 3,02±0,66 idi. Grup II L/b oranları erken dönem 3,52±0,96, geç dönem 2,63±0,63 olarak saptandı (p>0,05). BSC Grup I’de %79,6±2,5 ve Grup II’de %77,5±1,1 idi (p<0,05).

SONUÇ

CONCLUSION

In this rat model of TBI, lornoxicam reduced brain edema but did not affect BBB permeability.

Bu TBH sıçan modelinde lornoksikamın beyin ödemini azalttığı ancak KBB geçirgenliğini etkilemediği görülmüştür.

Key Words: Blood brain barrier; brain edema; lornoxicam; traumatic brain injury.

Anahtar Sözcükler: Kan beyin bariyeri; beyin ödemi; lornoksikam; travmatik beyin hasarı.

Departments of 1Anesthesiology and Intensive Care, 2 Nuclear Medicine, 3Neurosurgery, Celal Bayar University Faculty of Medicine, Manisa, Turkey.

Celal Bayar Üniversitesi Tıp Fakültesi, 1Anesteziyoloji ve Yoğun Bakım Anabilim Dalı, 2Nükleer Tıp Anabilim Dalı, 3 Nöroşirürji Anabilim Dalı, Manisa.

Correspondence (İletişim): İsmet Topçu, M.D. Güzelyurt Mahallesi, Tarzan Bulvarı, No: 88, Öncü Sitesi, 45030 Manisa, Turkey.

Tel: +90 - 236 - 236 03 30 / 1006 e-mail (e-posta): topcuismet@yahoo.com

294

Lornoxicam in brain trauma in rats

Head trauma frequently results in death or in critical conditions that lead to long-term disability and rehabilitative treatment. Brain injuries are found in approximately 85% of victims who die in traffic accidents.[1] The overall mortality rate due to severe head trauma is 35%, and this is generally due to cerebral edema and increased intracranial pressure.[2] The primary tissue damage caused by the mechanical effects of head trauma cannot be treated,[3] but efforts are made to modify the processes and minimize the consequences of secondary brain injury that occurs within minutes, hours, or days after the trauma.

[4-6] Posttraumatic brain edema is one of the pathophysiologic events occurring late as a secondary injury mechanism, and is thought to be generated in part by vasogenic edema due to blood brain barrier (BBB) breakdown and in part by cytotoxic edema.[7] Increases in brain cyclooxygenase-2 (COX-2) are associated with the central inflammatory response and delayed neuronal death, both of which cause secondary insults after traumatic brain injury (TBI).

[8,9] Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be neuroprotective in models of brain injury.[10,11] Lornoxicam is a potent analgesic and NSAID that inhibits COX-1/COX-2 in a balanced fashion; it is well tolerated and suitable for parenteral administration.

In this experimental study, the effects of lornoxicam on the BBB and development of brain edema in a rat model of diffuse TBI are elucidated.

MATERIALS AND METHODS The research protocol was approved by our University’s Committee on the Humane Care of Laboratory Animals. Twenty adult male Wistar albino rats, each weighing 220-250 g, were maintained under controlled environmental conditions (temperature 22 °C, humidity 65%, and light-dark cycle 12 hour (h):12 h) for a minimum of 4 days. All rats were fasted for 18 h before the experiments but were allowed free access to water until 20-30 minutes (min) before the start of the experiment. All experiments were started between 10 a.m. - 11 a.m.

After anesthesia with thiopental (30 mg kg-1 intraperitoneal [IP]), a median line scalp incision was made and the periosteum opened. A 10 mm diameter metal disc was glued to the cranium in the midline at the intersection of the coronal and lambdoid sutures. Diffuse closed head injury was induced by the method of Marmarou et al.[12] using a 450 g - 2 m weight-height impact onto the metal disc on the intact skull of the rats.

Twenty-four hours after head injury, the rats were randomly placed into one of two groups: Group I Cilt - Vol. 19 Sayı - No. 4

(n=10) served as the control group, to which 2 ml saline was administered IP, and Group II (n=10) was the lornoxicam group, to which 2 ml 1.3 mg kg-1 lornoxicam was administered IP. Twenty-four hours after the head trauma, 99mTc pentetate (DTPA) was injected via a 24-gauge cannula in the femoral vein at a dose of 37 MBq, and posterior planar images of each rat in the supine position were obtained with an Infinia gamma camera (GE Healthcare, Tirat, Hacermel, Israel) using a low-energy, high-resolution parallel-hole collimator with a 20% energy window centered at 140 keV. The field of view was a 256x256 matrix and had a scale of 5 zoom. Two images were obtained from each rat: one 5 min after isotope injection (early) and one 60 min after isotope injection (late). The ratios of proportional background were estimated using region-of-interest (ROI) analysis. ROIs were drawn to brain-to-background ratios (lesion/ background [L/b]).

After imaging of BBB permeability, rats were sacrificed by cervical dislocation, and brain tissues were removed from the cranium atraumatically. Tissue samples were weighed separately and then dried to a constant weight at 105 °C for 24 h. The brain water content (BWC) of each sample was calculated using wet-dry method: BWC%= 100x (wet weight - dry weight)/wet weight.

Statistical analyses were performed using MannWhitney U-test for significant differences between two groups. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) for Windows® version 14.0 (SPSS Inc., Chicago, IL, USA). Results are expressed as mean ± SD. P values less than 0.05 were considered to be statistically significant.

RESULTS Regarding BBB analysis, L/b in Group I was 3.76±0.46 (early) and 3.02±0.66 (late) and in Group II was 3.52±0.96 (early) and 2.63±0.63 (late) (p>0.05).

Differences between groups at each time point were not significant, but BBB permeability decreased between the early and late periods within groups (p<0.05, Table 1).

Regarding brain edema, BWC was 79.56±2.5% in Group I and 77.47±1.05% in Group II (p<0.05, Table 1). Early and late brain-to-background ratios are shown in Table 1. Examples of bio-distribution of Tc99m DTPA in dynamic and static (60th min) images are shown in Figure 1.

DISCUSSION In this experimental model, we found a significant decrease in brain edema and non-significant decrease in BBB permeability when lornoxicam was adminis295

Ulus Travma Acil Cerrahi Derg

Table 1. Brain-to-background ratios and BWC of groups (mean±SD)

Group I (control) n=10

Group II (lornoxicam) n=10

3.76±0.46 3.02±0.66 79.56±2.5

3.52±0.96 2.63±0.63 77.47±1.05

Brain-to-background activity ratios (L/bg) Early (5 min) Late (60 min) Brain water content (BWC)

p

0.47 0.19 0.026*

* p<0.05, when compared with between groups.

tered after TBI. The Marmarou mechanism for producing brain injury creates clinical features of diffuse axonal injury, biochemical characteristics of trauma, and brain edema 6-24 h after the trauma.[12] While the Marmarou model may not create all of the pathophysiological changes that are observed in head trauma patients, it is a standard model for testing therapies (some even later tested in Phase III trials in humans) for preventing or treating secondary brain injury after TBI. The BBB is a highly selective barrier that prevents the passage of many substances from the blood into the extracellular fluid of the brain, or into the brain cells, and vice versa. The increase in BWC after trauma is thought to be related to vasogenic edema due to disruption of the BBB. Although use of the spectrophotometric measurement of Evans blue in brain tissue for BBB analysis is very popular,[7,13] its methodological problems in previous studies may have contributed to over-estimates of tracer levels in the brain.[14,15] In our study, 99mTc pentetate, a non-diffusible tracer for the evaluation of BBB permeability, was used for assessing the integrity of the BBB. 99mTc pentetate penetrates the BBB only if the BBB has been disrupted. 99mTc-DTPA was also used in the past for brain

(a)

(b)

scintigraphy to detect brain infarcts as well as brain metastases.[16,17] Following TBI, arachidonic acid leaks from cell membranes and is converted into prostaglandins by cyclooxygenase. In animal experiments, prostaglandins have been found to increase in brain tissue after trauma.[9,18] COX-2 is a primary inflammatory mediator that converts arachidonic acid from damaged membranes into vasoactive prostaglandins, producing reactive oxygen species in the process.[8,18,19] Following TBI, these free radicals damage neural membranes, white matter, and the tight junctions that form the BBB. Peroxidative reactions may also be implicated in the progressive vascular damage that affects autoregulation and leads to arteriolar spasm and thrombosis. Thus, products of COX-2 likely play a role in secondary responses that may result in increased intracranial pressure, vasospasm, and ischemia, resulting in worsened outcomes.

Although COX-2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical-mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary in-

(c)

Fig. 1. (a) In vivo single-photon dynamic imaging of biodistribution of Tc99m DTPA. (b, c) The biodistribution and uptake of Tc99m DTPA were confirmed by in vivo static imaging (60th min).

(Color figure can be viewed in the online issue, which is available at www.tjtes.org).

296

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Lornoxicam in brain trauma in rats

juries to the brain that worsen behavioral outcome.[18] If the initial phase of COX-2 expression is beneficial, then delayed pharmacological treatment with steroids or COX-2-specific inhibitors could result in better outcomes, and may lead to new clinical treatment paradigms.[18] Many studies have been performed in recent years using COX inhibitors to prevent cerebral damage after head trauma.[10,11] Major targets of COX inhibition are cerebral vasculature, COX-2 release from neurons and neuroinflammatory response.[20] Studies have found that all three targets can be modified with appropriate treatment. Indomethacin significantly reduces the incidence of post-ischemic BBB disruption in the early period but does not have a significant effect on post-ischemic brain edema.[10] In vivo, rofecoxib has been found to prevent excitotoxic neuronal damage.[11] Meloxicam, a COX-2 inhibitor, has been found to preserve BBB permeability, decrease anti-inflammatory activity, and decrease brain edema in a model of diffuse TBI.[21] The central nervous system inflammatory reaction occurring after aneurysmal subarachnoid hemorrhage and intracerebral hemorrhage involves the upregulation of numerous cytokines and prostaglandins.[22,23] After intracerebral hemorrhage, COX inhibition with celecoxib, a selective COX-2 inhibitor, decreases brain edema, inflammation, and perihematomal cell death by decreasing generation of prostaglandin E2.[23] This is the first study in the literature to test the effects of lornoxicam on brain edema and BBB permeability in an animal model of TBI. In this model, lornoxicam reduced brain edema but did not have a significant effect on BBB permeability.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 1989;15:4959.

2. Lu J, Marmarou A, Choi S, Maas A, Murray G, Steyerberg EW; Impact and Abic Study Group. Mortality from traumatic brain injury. Acta Neurochir Suppl 2005;95:281-5.

3. McIntosh TK. Novel pharmacologic therapies in the treatment of experimental traumatic brain injury: a review. J Neurotrauma 1993;10:215-61.

4. McIntosh TK, Juhler M, Wieloch T. Novel pharmacologic strategies in the treatment of experimental traumatic brain injury: 1998. J Neurotrauma 1998;15:731-69.

5. Faden AI, Salzman S. Pharmacological strategies in CNS trauma. Trends Pharmacol Sci 1992;13:29-35.

6. Golding EM. Sequelae following traumatic brain injury.

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The cerebrovascular perspective. Brain Res Brain Res Rev 2002;38:377-88.

7. Esen F, Erdem T, Aktan D, Kalayci R, Cakar N, Kaya M, et al. Effects of magnesium administration on brain edema and blood-brain barrier breakdown after experimental traumatic brain injury in rats. J Neurosurg Anesthesiol 2003;15:11925.

8. Ellis EF, Police RJ, Rice LY, Grabeel M, Holt S. Increased plasma PGE2, 6-keto-PGF1 alpha, and 12-HETE levels following experimental concussive brain injury. J Neurotrauma 1989;6:31-7.

9. Dewitt DS, Kong DL, Lyeth BG, Jenkins LW, Hayes RL, Wooten ED, et al. Experimental traumatic brain injury elevates brain prostaglandin E2 and thromboxane B2 levels in rats. J Neurotrauma 1988;5:303-13.

10. Ting P. Indomethacin attenuates early postischemic vasogenic edema and cerebral injury. Adv Neurol 1990;52:119-26.

11. Hewett SJ, Silakova JM, Hewett JA. Oral treatment with rofecoxib reduces hippocampal excitotoxic neurodegeneration.

J Pharmacol Exp Ther 2006;319:1219-24.

12. Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 1994;80:291-300.

13. Chan PH, Yang GY, Chen SF, Carlson E, Epstein CJ. Coldinduced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase. Ann Neurol 1991;29:482-6.

14. Louin G, Marchand-Verrecchia C, Palmier B, Plotkine M, Jafarian-Tehrani M. Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury. Neuropharmacology 2006;50:182-90.

15. Habgood MD, Bye N, Dziegielewska KM, Ek CJ, Lane MA, Potter A, et al. Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci 2007;25:231-8.

16. Barth A, Haldemann AR, Reubi JC, Godoy N, Rösler H, Kinser JA, et al. Noninvasive differentiation of meningiomas from other brain tumours using combined 111Indiumoctreotide/99mtechnetium-DTPA brain scintigraphy. Acta Neurochir (Wien) 1996;138:1179-85.

17. Lorberboym M, Lampl Y, Sadeh M. Correlation of 99mTcDTPA SPECT of the blood-brain barrier with neurologic outcome after acute stroke. J Nucl Med 2003;44:1898-904.

18. Strauss KI, Barbe MF, Marshall RM, Raghupathi R, Mehta S, Narayan RK. Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic brain injury in the rat. J Neurotrauma 2000;17:695-711.

19. Kontos HA, Dietrich WD, Wei EP, Ellis EF, Povlishock JT. Abnormalities of the cerebral microcirculation after traumatic injury: the relationship of hypertension and prostaglandins. Adv Exp Med Biol 1980;131:243-56.

20. Hurley SD, Olschowka JA, O’Banion MK. Cyclooxygenase inhibition as a strategy to ameliorate brain injury. J Neurotrauma 2002;19:1-15.

21. Hakan T, Toklu HZ, Biber N, Ozevren H, Solakoglu S, Demirturk P, et al. Effect of COX-2 inhibitor meloxicam against traumatic brain injury-induced biochemical, histopathological changes and blood-brain barrier permeability.

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Neurol Res 2010;32:629-35.

22. Ayer R, Jadhav V, Sugawara T, Zhang JH. The neuroprotective effects of cyclooxygenase-2 inhibition in a mouse model of aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl 2011;111:145-9.

298

23. Chu K, Jeong SW, Jung KH, Han SY, Lee ST, Kim M, et al.

Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death. J Cereb Blood Flow Metab 2004;24:92633.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):299-304

Experimental Study

Deneysel Çalışma doi: 10.5505/tjtes.2013.64176

Genotoxicity of fixation devices analyzed by the frequencies of sister chromatid exchange Fiksasyon araçlarının genotoksisitesinin kardeş kromatit değişim sıklığıyla analizi Barış Altuğ AYDİL,1 Hülya KOÇAK BERBEROĞLU,1 Sükrü ÖZTÜRK,2 Kıvanç CEFLE,2 Şükrü PALANDÜZ,2 Haluk ERKAL2 BACKGROUND

AMAÇ

Metal alloys utilized in the management of jaw fractures may exert genotoxic effects. Our purpose was to compare the genotoxicity of intermaxillary fixation devices containing nickel and chromium to that of titanium miniplates utilized in treatment of jaw fractures through the analysis of sister chromatid exchange.

Çene kırıklarının tedavisinde kullanılan metal alaşımları genotoksik etkilere yol açabilir. Amacımız, kardeş kromatit değişim sıklığının analiziyle, çene kırıklarının tedavisinde kullanılan nikel-krom içerikli intermaksiller fiksasyon araçları ve titanyum miniplakların genotoksisitelerini karşılaştırmaktır.

METHODS

GEREÇ VE YÖNTEM

In this prospective study, in a total of 28 non-smoker patients (10 females, 18 males; mean age 33.43±10.76; range 15 to 60 years) with jaw fractures, 14 were treated with intermaxillary fixation by administration of nickel-chromium wire and arch bar and 14 with titanium miniplates to investigate the genotoxicity of different metal alloys. The outcome variable was the frequency of sister chromatide exchange in peripheral lymphoctyes, determined through the analysis of venous blood samples obtained preoperatively and 4 to 6 weeks postoperatively.

Bu ileriye yönelik çalışmada, farklı metal alaşımlarının genotoksisitesini araştırmak için çene kırığı bulunan ve sigara içmeyen toplam 28 hastanın (10 kadın, 18 erkek; ortalama yaş 33,43±10,76; dağılım 15-60 yıl) 14’ünde nikel-krom içerikli ark bar ve tel uygulanmasıyla intermaksiller fiksasyon gerçekleştirilirken diğer 14’üne titanyum miniplak tedavisi uygulandı. Sonuç değişkeni ameliyat öncesinde ve ameliyattan dört-altı hafta sonra alınan venöz kan örneklerindeki periferal lenfositlerde görülen kardeş kromatit değişiminin sıklığıydı.

RESULTS

BULGULAR

The frequency of the average sister chromatid exchange was found to be significantly higher in patients treated with the nickel-chromium intermaxillary fixation devices than those treated by titanium miniplates (1.29±0.29 vs.

0.46±0.39, p<0.001).

CONCLUSION

Although titanium miniplate osteosynthesis is an invasive technique in comparison with the nickel-chromium-containing intermaxillary fixation devices, titanium seems to exert less genotoxic effect than the nickel-chromium alloy.

However, this finding should be supported in clinical studies with a larger sampling size.

Ortalama kardeş kromatit değişim sıklığının nikel-krom içerikli intermaksiller fiksasyon araçlarıyla tedavi edilen hastalarda titanyum miniplaklarla tedavi edilenlere oranla önemli ölçüde daha yüksek olduğu gözlendi (1,29±0,29 ve 0,46±0,39, p<0,001).

SONUÇ

Her ne kadar titanyum miniplak osteosentezi nikel-krom içerikli intermaksiller fiksasyon araçlarına kıyasla daha invaziv bir teknik ise de, titanyumun nikel-krom alaşımından daha az genotoksik etkiye yol açtığı görülmektedir. Ancak bu bulgu daha geniş örneklem büyüklüğüyle gerçekleştirilen klinik çalışmalarla desteklenmelidir.

Key Words: Genotoxicity; intermaxillary fixation; nickel-chromium alloy; sister chromatid exchange; titanium; titanium miniplate osteosynthesis.

Anahtar Sözcükler: Genotoksisite; intermaksiller fiksasyon; nikel-krom alaşımı; kardeş kromatit değişimi; titanyum; titanyum miniplak osteosentezi.

1 Department of Oral and Maxillofacial Surgery, Istanbul University Faculty of Dentistry, Istanbul; 2 Department of Internal Medicine, Division of Genetics, Istanbul University Faculty of Medicine, Istanbul, Turkey.

1 İstanbul Üniversitesi Diş Hekimliği Fakültesi, Ağız Diş ve Çene Cerrahisi Anabilim Dalı, İstanbul; 2 İstanbul Üniversitesi Tıp Fakültesi, Dahiliye Anabilim Dalı, Tıbbi Genetik Bölümü, İstanbul.

Correspondence (İletişim): Barış Altuğ Aydil, M.D. İstanbul Üniversitesi Diş Hekimliği Fakültesi, Ağız Diş ve Çene Cerrahisi Anabilim Dalı, Çapa, İstanbul, Turkey.

Tel: +90 - 212 - 414 25 78 e-mail (e-posta): barisaydil@merset.com.tr

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Fracture is the partial or total loss of bone integrity due to a trauma or a pathologic condition.[1,2] In the treatment of fractures, the main goal is to restore the functional integrity by bringing the fractured portions of the jaw into normal anatomical position, which is also termed as fracture reduction.[3,4] This is followed by fixation through which the fractured parts are held in their anatomical positions until the healing is complete.[5-7] The materials used for intermaxillary fixation (IMF) encompass arch bars, ligature wires, pins, screws, and plates, which are made of various metals.

The fixative elements such as plates, pins, wires, and screws submerged in the bone are composed of different metals that may lead to local or systemic reactions over time.[7-10] While several studies[8,11,12] have reported on the local tissue reactions led by metals left in situ after healing, there are only a few reports on the systemic effects of metallic elements used for fracture treatment.[12-16] The analysis of sister chromatid exchange (SCE) is a sophisticated cytomolecular technique used in research studies for determination of genotoxicity.[17-20] The analysis of SCE indicates clastogenic, genotoxic and genetic instabilities in chromosomes as demonstrated by discrete stainings in the symmetrical segments of the chromatids.[19-22] In various lesions, SCE may increase under the influence of ultraviolet light and X-ray radiation, chemicals or even spontaneously. In determination of the mutagenic effects or genotoxic potential of chemicals, SCE is more sensitive than chromatid breaks, gaps and the figures of exchange. Mutagens and carcinogens can cause significant increase in the frequency of SCE, even in concentrations that would not cause chromosome breaks. SCE is thought to take place in the replication point, and SCE analysis is a technique used to study the effect of many chemical mutagens.[19,20,22-24] In this study, our main purpose was to investigate the genotoxicity of different metal alloys used for the fixation of jaw fractures through the analysis of SCE.

MATERIALS AND METHODS This prospective study was carried out in a total of 28 patients with jaw fractures (10 females, 18 males; all non-smokers; mean age 33.43Âą10.76; range 15 to 60 years) who referred to the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Istanbul University, Istanbul, Turkey, between January 2002 and June 2008. The patients with a systemic infection, malignant disorder, history of cytotoxic or narcotic drug administration, smokers, and workers who could have been subjected to metal dusts were not included in the study. All patients signed an informed consent, prepared in accordance with the Declaration of Hel300

sinki, which was reviewed and approved by the local ethics committee of our institution.

In the treatment of 14 patients through IMF procedure, a durable, stainless and flexible arch bar containing aluminum (58-65%), chromium (17-30%), iron (15-20%), and nickel (13-16%) and a ligature wire composed of vitallium (30-40%), chromium (17-25%), iron (15-20%), nickel (13-16%), and molybdenum (2.25-3.5%) were used. The metal elements utilized for IMF were left in place for 4-6 weeks. In the treatment of 14 patients with titanium miniplate osteosynthesis (TMO), a durable, stainless and biocompatible grade I-IV amorphous titanium alloy miniplate containing titanium (99.5%), iron (0.2%), oxygen (0.1%), carbon (0.08%), nitrogen (0.05%), and hydrogen (0.013%) was utilized. Generally, the miniplates with 4 or 6 holes (20x2x0.9 mm in dimension) were preferred and stabilized using titanium screws in lengths of 5, 7, 9, 11 or 13 mm.

In the venous blood samples obtained before and 4-6 weeks after the IMF and TMO surgery, the frequencies of SCE in the peripheral blood lymphocytes were investigated. The peripheral blood lymphocytes were cultured for 72 hours in dark medium containing 0.5 Âľg/ml bromodeoxyuridine (BrdU), which was added 24 hours after the initial culturing process. The metaphase plates were obtained after the standard harvest procedure and stained by Fluorescent-plusGiemsa (FPG) technique. Using a light microscope (Leitz-Ortoplan), the counts of SCE and their distributions in chromosomes were evaluated after selecting clear-cut metaphases under x100 magnification. A terminal change was counted as a single change and the interstitial changes as dual changes. Through the assessment of 30 metaphases in each case, the average SCE per metaphase before and after treatment was calculated by dividing the total count of SCE by the number of metaphases analyzed (Fig. 1).

Fig. 1. Arrows indicating the sister chromatid exchange in chromosomal sites.

Temmuz - July 2013

Genotoxicity of fixation devices analyzed by the frequencies of sister chromatid exchange

12.5

SCE bt

SCE at

Difference (SCE [at]-SCE [bt])

10 7.5 5 2.5 0 -2.5

IMF

TMO

Fig. 2. Diagram showing the average frequencies of SCE in patients treated with nickel chromium-containing intermaxillary fixation (IMF) devices or titanium miniplate osteosynthesis (TMO). The average frequency of SCE in the IMF patients is significantly higher than in TMO patients (p=0.001, Mann-Whitney U-test).

The Mann-Whitney U-test and the Wilcoxon signed ranks tests were performed for the statistical analyses of the data obtained from independent and dependent variables, respectively. The Statistical Package for the Social Sciences (SPSS) software (version 15; SPSS, Inc., Chicago, IL) was used for statistical analyses, and a p value less than 0.05 was considered statistically significant.

RESULTS Of the 28 fractures treated, 25 were mandibular fractures and 3 were maxillary fractures. In 14 patients, 12 unilateral fractures and 2 bilateral fractures were treated by IMF procedure. In 14 patients, TMO procedure was carried out for the treatment of 5 unilateral, 5 bilateral and 4 complex fractures (Table 1).

Before the treatment, there was no statistically signifiTable 1. The types of fractures and treatments Type of fracture Mandibular fracture Maxillary fracture Total

25 3 28

Type of treatment

TMO

IMF

Unilateral fracture Bilateral fracture Complex fracture Total

5 5 4 14

12 2 14

TMO: Titanium miniplate osteosynthesis; IMF: Intermaxillary fixation.

Cilt - Vol. 19 Sayı - No. 4

cant difference between the average frequency of SCE in the peripheral lymphocytes of the patients treated

by IMF or TMO (8.25±0.96 vs. 8.45±1.57, p=0.963).

After the treatment, the average frequency of SCE significantly changed in both groups, reaching 9.54±0.93 (p=0.001) and 8.92±1.6 (p=0.001) in IMF patients and TMO patients, respectively (Tables 2, 3). The average frequency of SCE in the peripheral lymphocytes was significantly higher in the patients treated by IMF than in those treated by TMO (1.29±0.29 vs. 0.46±0.39, p<0.001) (Fig. 2).

DISCUSSION There is still controversy as to whether the fixation devices should be removed or left in situ due to their possible local tissue reactions in addition to any systemic effects. Therefore, the genotoxic potential of different metal alloys used for fracture fixation has been investigated in research studies.

In this study, the patients treated with IMF were probably exposed to nickel and chromium ions released from the arch bar and ligature wire. The increase in the frequency of SCE in peripheral lymphocytes of these patients was statistically significant (1.29±0.29 vs. 0.46±0.39, p<0.001). This was consistent with the findings of other studies carried out in patients exposed to nickel and chromium ions through the systemic route or inhalation.[22-25] Torgersen et al.[26] reported an increase in transformation of lymphocytes and allergic reactions due to nickel alloy in patients treated by IMF. Merritt and Brown[27] indicated that particularly the ions of chromium, cobalt and nickel released from 301

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Table 2. Demographic data and the frequency of SCE observed before and after treatment in IMF patients No.

Patients

Age

Gender

Type of treatment

SCEbt

SCEat

Difference (SCEat)-(SCEbt)

1 2 3 4 5 6 7 8 9 10 11 12 13 14

AC BB CD HS IV MC MB NK NU ST SE TA MU RC

31 37 22 35 42 23 18 36 60 32 36 35 36 21

Male Male Male Male Male Female Male Female Male Female Female Male Male Male

Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation Intermaxillary fixation

7.2 8.6 7.2 8.7 7.8 8.9 10.2 6.8 9.2 7.9 7.6 9.2 8.7 7.5 8.25±0.96

9.2 9.8 8.4 9.8 8.7 10.2 11.3 7.9 10.4 9.4 9.4 10.6 9.9 8.6 9.54±0.93

2.0 1.2 1.2 1.1 0.9 1.3 1.1 1.1 1.2 1.5 1.8 1.4 1.2 1.1 1.29±0.29 (Mean±StD)

SCEbt: Sister chromatid exchange before treatment; SCEat: Sister chromatid exchange after treatment; StD: Standard deviation.

Table 3. Demographic data and the frequency of SCE observed before and after treatment in TMO patients No.

Patients

Age

Gender

Type of treatment

SCEbt

SCEat

Difference (SCEat)-(SCEbt)

15 16 17 18 19 20 21 22 23 24 25 26 27 28

AM AT AC BC ES EC FC GU HB KA MT MO SI MM

19 21 43 41 43 35 15 42 39 15 50 29 37 43

Male Male Female Male Male Male Male Female Female Female Male Male Female Female

TMO TMO TMO TMO TMO TMO TMO TMO TMO TMO TMO TMO TMO TMO

9.8 10.7 10.02 7.9 6.8 11.0 10.1 8.7 6.8 7.4 6.9 7.2 8.3 6.8 8.45±1.57

10.2 11.0 11.0 8.6 7.6 11.2 11.0 8.4 7.2 7.2 7.8 7.9 8.7 7.1 8.92±1.6

0.4 0.3 0.98 0.7 0.8 0.2 0.9 -0.3 0.4 -0.2 0.9 0.7 0.4 0.3 0.46±0.39 (Mean±StD)

SCEbt: Sister chromatid exchange before treatment; SCEat: Sister chromatid exchange after treatment; TMO: Titanium miniplate osteosynthesis; StD: Standard deviation.

a metal alloy through corrosion have toxic effects. The toxic ions of cobalt and nickel are excreted quickly through the urinary tract whereas the ions of chromium are stored in tissues and slowly migrate to the urinary tract. In comparison with the controls consisting of healthy, smoker and non-smoker subjects, Jelmert et al.[24] found a statistically significant increase in the frequency of SCE in the peripheral lymphocytes of the 42 workers directly exposed to nickel and chromium ions in a welding factory manufacturing metal arches containing stainless steel. In an in-vitro study, Katsifis 302

et al.[28] incubated the cell cultures containing NiSO4 and chromium with the heparinized blood samples from non-smokers who were not previously exposed to the dusts of heavy metals and not showing signs of DNA damage. They indicated that nickel (II) and chromium (VI) increased the frequency of SCE in peripheral lymphocytes. In our study, attention was paid to eliminate the smokers, those patients ever exposed to cytotoxic drugs, and workers who could have been subjected to metal dusts, since smoking, cytotoxic drugs and inhaled metal dusts could lead to an increase Temmuz - July 2013

Genotoxicity of fixation devices analyzed by the frequencies of sister chromatid exchange

in the frequency of SCE.[29,30] Nevertheless, food additives and preservatives such as sodium benzoate and potassium benzoate commonly used as antimicrobial substances in many kinds of foods (e.g. marinated fish, fruit-based fillings, jam, salad dressing, soft drinks, and beer) have been reported to significantly increase the frequency of SCE in-vitro.[31] Therefore, the possible role of these substances should not be disregarded with respect to the non-significantly and significantly higher frequencies of SCE in the TMO and IMF patients, respectively.

In summary, the increase in the frequency of SCE was significant when arch bars and wires containing nickel and chromium were used for IMF, which is a non-invasive technique. On the other hand, the change in the frequency of SCE was not significant when the invasive TMO technique was performed with the use of plates and screws containing titanium alloy. The long-term follow-up of these patients was not possible due to the high costs of test kits used for determination of the SCE frequency.

In conclusion, 4 to 6 weeks after treatment, the materials containing nickel and chromium alloy used in IMF significantly increased the frequency of SCE in peripheral blood lymphocytes. On the other hand, the plates and screws containing titanium alloy used in TMO did not lead to significant changes in the frequency of SCE after treatment. Even though our results indicate that titanium alloys are less genotoxic than nickel and chromium alloys, this should be confirmed in clinical studies with a larger sampling size.

Conflict-of-interest issues regarding the authorship or article: None declared.

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Anat 1988;183:1-44.

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9. Roccia F, Tavolaccini A, Dell’Acqua A, Fasolis M. An audit of mandibular fractures treated by intermaxillary fixation using intraoral cortical bone screws. J Craniomaxillofac Surg 2005;33:251-4.

10. Brown JS, Grew N, Taylor C, Millar BG. Intermaxillary fixation compared to miniplate osteosynthesis in the management of the fractured mandible: an audit. Br J Oral Maxillofac Surg 1991;29:308-11.

11. Fordyce AM, Lalani Z, Songra AK, Hildreth AJ, Carton AT, Hawkesford JE. Intermaxillary fixation is not usually necessary to reduce mandibular fractures. Br J Oral Maxillofac Surg 1999;37:52-7.

12. Thor A, Andersson L. Interdental wiring in jaw fractures: effects on teeth and surrounding tissues after a one-year follow-up. Br J Oral Maxillofac Surg 2001;39:398-401.

13. Jones JK, Van Sickels JE. Rigid fixation: a review of concepts and treatment of fractures. Oral Surg Oral Med Oral Pathol 1988;65:13-8.

14. Laine P, Kontio R, Lindqvist C, Suuronen R. Are there any complications with bioabsorbable fixation devices? A 10 year review in orthognathic surgery. Int J Oral Maxillofac Surg 2004;33:240-4.

15. Langford RJ, Frame JW. Surface analysis of titanium maxillofacial plates and screws retrieved from patients. Int J Oral Maxillofac Surg 2002;31:511-8.

16. Iizuka T, Lindqvist C. Rigid internal fixation of mandibular fractures. An analysis of 270 fractures treated using the AO/ ASIF method. Int J Oral Maxillofac Surg 1992;21:65-9.

17. Celi K A, Akbaş E. Evaluation of sister chromatid exchange and chromosomal aberration frequencies in peripheral blood lymphocytes of gasoline station attendants. Ecotoxicol Environ Saf 2005;60:106-12.

18. Garry VF, Nelson RL, Whorton EP, Wiencke JK. Chromosomal aberrations and sister-chromatid exchanges in tool and die workers. Mutat Res 1989;225:1-9.

19. Gennart JP, Baleux C, Verellen-Dumoulin C, Buchet JP, De Meyer R, Lauwerys R. Increased sister chromatid exchanges and tumor markers in workers exposed to elemental chromium-, cobalt- and nickel-containing dusts. Mutat Res 1993;299:55-61.

20. Wise JP, Orenstein JM, Patierno SR. Inhibition of lead chromate clastogenesis by ascorbate: relationship to particle dissolution and uptake. Carcinogenesis 1993;14:429-34.

21. Sorsa M, Ojajärvi A, Salomaa S. Cytogenetic surveillance of workers exposed to genotoxic chemicals: preliminary experiences from a prospective cancer study in a cytogenetic cohort. Teratog Carcinog Mutagen 1990;10:215-21.

22. Zakharov AF, Egolina NA. Differential spiralization along mammalian mitotic chromosomes. I. BUdR-revealed differentiation in Chinese hamster chromosomes. Chromosoma 1972;38:341-65.

23. Savarino L, Stea S, Granchi D, Visentin M, Ciapetti G, Donati ME, et al. Sister chromatid exchanges and ion release in patients wearing fracture fixation devices. J Biomed Mater Res 2000;50:21-6.

24. Jelmert O, Hansteen IL, Langård S. Chromosome damage in lymphocytes of stainless steel welders related to past and 303

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current exposure to manual metal arc welding fumes. Mutat Res 1994;320:223-33.

25. Sahu RK, Katsifis SP, Kinney PL, Christie NT. Ni(II) induced changes in cell cycle duration and sister-chromatid exchanges in cultured human lymphocytes. Mutat Res 1995;327:217-25.

26. Torgersen S, Gilhuus-Moe OT, Gjerdet NR. Immune response to nickel and some clinical observations after stainless steel miniplate osteosynthesis. Int J Oral Maxillofac Surg 1993;22:246-50.

27. Merritt K, Brown SA. Distribution of cobalt chromium wear and corrosion products and biologic reactions. Clin Orthop Relat Res 1996:233-43.

28. Katsifis SP, Kinney PL, Hosselet S, Burns FJ, Christie NT. Interaction of nickel with mutagens in the induction of sis-

304

ter chromatid exchanges in human lymphocytes. Mutat Res 1996;359:7-15.

29. Oztürk S, Vatansever S, Cefle K, Palanduz S, Güler K, Erten N, et al. Acute wood or coal exposure with carbon monoxide intoxication induces sister chromatid exchange. J Toxicol Clin Toxicol 2002;40:115-20.

30. Wong RH, Wang JD, Hsieh LL, Du CL, Cheng TJ. Effects on sister chromatid exchange frequency of aldehyde dehydrogenase 2 genotype and smoking in vinyl chloride workers.

Mutat Res 1998;420:99-107.

31. Zengin N, Yüzbaşıoğlu D, Unal F, Yılmaz S, Aksoy H. The evaluation of the genotoxicity of two food preservatives: sodium benzoate and potassium benzoate. Food Chem Toxicol 2011;49:763-9.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):305-312

Experimental Study

Deneysel Çalışma doi: 10.5505/tjtes.2013.98223

Karın içi adezyon önleyici %4'lük ikodekstrin solüsyonunun gastrointestinal sistem anastomozları üzerine etkisi Effects of abdominal adhesion-preventing 4% icodextrin solution on healing of bowel anastomoses Okay KOÇ,1 Ahmet DAĞ,2 Ahmet Koray ÖCAL,2 Mustafa Musa DİRLİK,2 Ülkü ÇÖMELEKOĞLU,3 Lülüfer Tamer GÜMÜŞ,4 Ebru SERİNSÖZ,5 Emine Arzu KANIK,6 Hamdi AKÇA2 AMAÇ

BACKGROUND

%4’lük ikodekstrin solüsyonunun adezyonu önlemedeki etkinliğini ve anastomoz iyileşmesi üzerine etkisini, biyokimyasal parametrelerle birlikte ortaya koymak.

We aimed to introduce the efficiency of 4% icodextrin solution on preventing adhesions and its effect on anastomotic healing, together with biochemical parameters.

GEREÇ VE YÖNTEM

METHODS

Toplam 40 sıçan 10’ar sıçandan oluşan dört gruba ayrıldı.

Grup A (abrazyon+ikodekstrn), Grup B (abrazyon), Grup C (anastomoz+ikodekstrin), Grup D (anastomoz). Gruplarda adezyon skoru, anastomoz patlama basıncı, histopatolojik inceleme, doku hidroksiprolin düzeyi, miyeloperoksidaz (MPO), nitrik oksit (NO) ve malondialdehit (MDA) değerlerine bakıldı.

In total, 40 rats were divided into four groups of 10 rats each as Group A (abrasion+icodextrin), Group B (abrasion), Group C (anastomosis+icodextrin), and Group D (anastomosis). Adhesion grade, anastomotic bursting pressure, histopathological analysis, tissue hydroxyproline level, and serum myeloperoxidase (MPO), nitric oxide (NO), and malondialdehyde (MDA) values were examined.

BULGULAR

RESULTS

Adezyon skoru A grubunda B grubuna oranla, C grubunda D grubuna oranla daha düşük bulundu (p=0,003577, p=0,001612). Grup C ve Grup D arasında anastomoz iyileşmesi arasında fark yoktu (p=0,816). Hidroksiprolin düzeyi A grubunda B grubuna oranla, C grubunda D grubuna oranla daha yüksekti (p=0,001, p=0,0001). NO ve MDA düzeyleri bakımından Grup A ve Grup B arasında fark yoktu, Grup C’de ise D grubuna oranla daha düşüktü (p=0,434, p=0,001, p=0,116, p=0,018). MPO değerleri Grup A’da B grubuna oranla, Grup C’de, Grup D’ye oranla daha düşük saptandı (p=0,0001).

SONUÇ

%4’lik ikodekstrin solüsyonunun anastomoz iyileşmesini olumsuz yönde etkilemeden adezyon oluşumunu belirgin olarak azalttığı biyokimyasal parametreler, histopatolojik inceleme ve adezyon skorlaması ile ortaya kondu.

Anahtar Sözcükler: Adezyon; ameliyat sonrası komplikasyonlar; ikodekstrin.

1 Diyarbakır Eğitim ve Araştırma Hastanesi, Gatroenterolojik Cerrahi Kliniği, Diyarbakır; Mersin Üniversitesi Tıp Fakültesi, 2Genel Cerrahi Anabilim Dalı, 3 Biyofizik Anabilim Dalı, 4Tıbbi Biyokimya Anabilim Dalı, 5 Patoloji Anabilim Dalı, 6Biyoistatistik Anabilim Dalı, Mersin.

Adhesion score was significantly lower in Group A than in Group B and significantly lower in Group C than in Group D (p=0.003577, p=0.001612). No difference in anastomoses healing was determined between Group C and Group D (p=0.816). Hydroxyproline level was significantly higher in Group A than in Group B and significantly higher in Group C than in Group D (p=0.001, p=0.0001). There were no differences in NO and MDA levels between Group A and Group B, but values were significantly lower in Group C than in Group D (p=0.434, p=0.001, p=0.116, p=0.018). MPO level was significantly lower in Group A than in Group B and significantly lower in Group C than in Group D (p=0.0001, p=0.0001).

CONCLUSION

Based on our results, 4% icodextrin solution evidently decreased the formation of adhesion without negatively affecting the anastomotic healing. We also reported herein the biochemical and histopathological results and adhesion scores.

Key Words: Adhesions; postoperative complications; icodextrin.

1 Department of Gastroenterologic Surgery, Diyarbakır Training and Research Hospital, Diyarbakir; Departments of 2General Surgery, 3Biophysics, 4 Medical Biochemistry, 5Pathology, 6Biostatistics, Mersin University Faculty of Medicine, Mersin, Turkey.

İletişim (Correspondence): Dr. Okay Koç. Diyarbakır Eğitim ve Araştırma Hatanesi, Elazığ Yolu, 10. km, 21000 Diyarbakır, Turkey.

Tel: +90 - 412 - 258 00 60 e-posta (e-mail): okaykocdr@yahoo.com.tr

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Ulus Travma Acil Cerrahi Derg

Günümüzde adezyon oluşumunun en önemli nedeni geçirilmiş karın cerrahisidir.[1] Değişik nedenlerle karın cerrahisi geçirmiş olan hastaların %12 ile %17’sinde ameliyat sonrası erken ya da geç dönemde serozal adezyonlara bağlı subileus tablosu geliştiği bildirilmiştir.[1] Adezyon önleyici ajan olarak kullanılan %4’lük ikodekstrin solüsyonunun adezyonu önlemede etkin olduğunu belirten çalışmalar olduğu gibi aksi yönde görüş bildiren çalışmalar da vardır.[2-6] Gastrointestinal sistem anastomozları üzerine etkisi konusunda ise literatürde üç adet deneysel çalışmaya ulaşılmıştır.[7-9] Çalışmaların ikisinde anastomoz iyileşmesini olumsuz yönde etkilemediği belirtilirken bir tanesinde aksi yönde görüş bildirilmiştir. Bu üç çalışmada anastomoz iyileşmesi anastomoz patlama basıncı ölçümü, histopatolojik inceleme ve hidroksiprolin düzeyi ölçümümü yöntemlerinden biri veya birkaçı ile değerlendirilmiş, ancak, miyeloperoksidaz (MPO), nitrik oksit (NO) ve malondialdehit (MDA) gibi enflamasyon şiddetini ve doku hasarını gösteren biyokimyasal parametreler kullanılmamıştır. Adezyon periton hasarına vücudun verdiği enflamatuvar yanıt sonrasında gelişmektedir.[10] Enflamatuvar yanıtın şiddeti artıkça yapışıklık artacaktır. Adezyonu önlediği düşünülen ajan gerçekten etkin ise daha az şiddette bir enflamatuvar yanıt ve sonrasında daha az doku hasarı beklenir.

Bu düşünceden hareketle bu çalışmada, adezyon skorlaması, anastomoz patlama basıncı, histopatolojik inceleme ve hidroksiprolin ölçümüne ek olarak oluşan enflamatuvar yanıtın şiddetini değerlendirmek, NO ve MPO, doku hasarını değerlendirmek amacıyla MDA değerlerine bakıldı. Böylece ikodekstrinin adezyonu önlemedeki etkinliğini, anastomoz iyileşmesi ve doku hasarına etkisini biyokimyasal parametrelerle destekleyerek değerlendirmeyi amaçladık.

GEREÇ VE YÖNTEM Bu çalışma, Hayvan Deneyleri Yerel Etik Kurulu’nca etik yönden uygun bulunarak “Guidelines in the use and care of laboratory animals” kuralları çerçevesinde yapılmıştır.[11] Deney hayvanları Ağırlıkları 160-250 gr arasında değişen 40 adet erkek, Wistar albino tipi sıçan çalışma kapsamına alın-

dı. Deney Hayvanları Mersin Üniversitesi Hayvan Laboratuvarı’nda 24 °C oda ısısında ve 12/12 saatlik gece gündüz siklusunda tutuldu. Kısıtlama yapılmadan standart sıçan yemi ve su ile beslendi.

Deneysel çalışma On’ar sıçandan oluşan dört grup oluşturuldu. Bütün deney gruplarında sıçanlara kas içine ketamin (Ketalar®, Eczacibası Warner Lambert Ilac AS, İstanbul, Turkey, 50-100 mg/kg) ve ksilazin 10 mg/kg indüksiyonun ardından orta hattan laparotomi yapıldı. A ve B gruplarında laparotomi sonrası çekumda abrazyon oluşturuldu. A grubunda abrazyon sonrası karın boşluğunu dolduracak kadar (5-10 cc) %4’lük ikodekstrin solüsyonu konulup karın 2/0 ipek dikişle kapatıldı. B grubunda çekum abrazyonu sonrasında herhangi bir ek işlem yapılmadan karın aynı şekilde kapatıldı. C ve D gruplarında ise laparotomi sonrası sol kolon distaline kesi yapıldı. Daha sonra 6/0 poliglaktin dikişle tek kat anastomoz oluşturuldu. C grubunda anastomoz sonrası karın içine karın boşluğunu dolduracak kadar (5-10 cc) %4’lük ikodekstrin solüsyonu konulup karın 2/0 ipek dikişlerle kapatıldı. D grubunda ise anastomoz sonrası solüsyon kullanılmadan karın 2/0 ipek dikişle kapatıldı. Sıçanlara yedinci günde relaparotomi yapıldı. Karın içi adezyonlar Leach ve arkadaşlarının derecelendirme sistemi ile derecelendirildi (Tablo 1).

A ve B gruplarında çekum duvarından hidroksiprolin ölçümü için doku örneği alındı. C ve D gruplarında anastomoz bölgesini içeren 6 cm’lik kolon segmenti rezeke edildi. Toraks açılarak intrakardiyak kan örneği alınmasının ardından sıçanlar sakrifiye edildi. Kan örnekleri 4000 rpm’de 10 dakika santrifüj edilerek serumları ayrıştırıldı. Serum örnekleri ölçüm yapılıncaya kadar -20 °C’de saklandı.

Patlama basıncı ölçüm tekniği Yedinci günde yapılan re-laparotomi’de anastomozun proksimal ve distalinden 3’er cm olmak üzere sol kolondan 6 cm’lik segment çıkartıldı. Çıkartılan segmentin her iki ucundan 8 gauce silikon kateterler lümene konulup 2/0 ipek ile sıkıca bağlandı. Bir uçtaki kateter şırınga pompasına, diğer uçtaki kateter basınç transducer’ine takıldı. Patlama basıncı ölçümü için şırınga pompasıyla (62-HF-0267-00, Abbott, Chicago, USA) 2 ml/dk’dan %0,9 sodyum klorür infüzyonu

Tablo 1. Leach ve arkadaşlarının adezyon skorlama sistemi Skor

Tip

Direnç

Yaygınlık (%)

1 2 3 4 5

Adezyon yok İnce adezyon Sert adezyon Keskin diseksiyon gerektiren adezyon Daha ileri derecede adezyon

– Kolay ayrılan adezyon Traksiyon gerektiren adezyon Sert diseksiyon gerektiren adezyon Daha ileri derecede adezyon

– 1-25 26-50 51-75 76-100

306

Temmuz - July 2013

Karın içi adezyon önleyici %4’lük ikodekstrin solüsyonunun gastrointestinal sistem anastomozları üzerine etkisi

Tablo 2. Deney sonuçları (ortalama değerler) A Ort.±SS

B Ort.±SS

p

C Ort.±SS

D Ort.±SS

p

0 (10) 0 (10) 2 – 3,479300±,893908 55,014±13,19944 6,6542±4,2231 0,1742±0,0436

0 (10) 0 (10) 6,25 – 2,03190±0,73879 68,1740±21,048 11,1460±3,1962 0,3646±0,10981

– – 0,0035 – 0,001 0,434 0,116 0,0001

0 (10) 1 (10) 4 162,5850±19624 3,98920±,775382 55,23±20,918 7,1949±5,5176 0,2077±0,06191

0 (10) 2 (10) 9 154,9280±45096 2,04740±,715435 91,350±20,917 13,2627±4,1929 0,3752±0,07024

– 0,531 0,0016 0,816 0,0001 0,001 0,018 0,0001

Grup

Yara inf. (%) Anast. kaçağı (%) Adezyon skoru Patlama basıncı Hidroksiprolin düzeyi NO düzeyi MDA değerleri MPO değerleri

Ort.: Ortalama; SS: Standart sapma; NO: Nitrik oksit; MDA: Malondialdehit; MPO: Miyeloperoksidaz.

yapıldı. Basınç disposable basınç transducer’ı ile monitörize edilip Hewlett-Packard recorder (Biopac MP100 Acquisition System, Version 3.5.7 Santa Barbara, USA) ile kaydedildi. Kaçağın oluştuğunu gösteren pik basınç patlama basıncı olarak değerlendirildi.

Hidroksiprolin analizi Çekum duvarından ve anastomoz bölgesinden alınan doku örnekleri analiz yapılıncaya kadar -200 °C’de saklandı. Analiz yapılmadan önce oda sıcaklığına çıkarıldı. 200 °C’de bir gece bırakılarak kurumaları sağlandı ve kuru ağırlıkları tartıldı. Daha sonra doku örnekleri 1 ml fosfat tamponu (PBS, pH 7,4) içerisinde homojenize edildi. Süpernatanda hidroksiprolin konsantrasyonu ölçüldü. Örneklerin absorbansları Varian Carry 50 Spektrofotometresinde ölçülerek miligram doku ağırlığı başına mikrogram hidroksiprolin miktarı olarak hesaplandı.[12] Nitrik oksit ölçümü Serum nitrik oksit düzeyi için okside son ürünleri olan nitrit/nitrat düzeyleri Griess reaksiyonu temel alınarak ölçüldü.[13] Eşit miktarda serum ve izo-ozmotik potasyum fosfat tamponu oda sıcaklığında 45 dakika 4000 rpm’de santrifüj edildi. Süpernatan toplandı ve nitrat içeriği nitrat redüktazla enzimatik olarak nitrite indirgendi: Nitrat + NADPH + H+ → nitrit + NADP+ + H 2O N-1-(naftil) etilen diyamin dihidroklorit, sülfanilamit ve inkübasyon solüsyonu 1:1:2 (v/v) oranında karıştırıldı ve kırmızı-mor renkli diyazo boyası oluştu: Nitrit + sülfanilamit + N-(1-naftil)-etilen diyamin diyazo boya.

Bu karışım oda sıcaklığında beş dakika inkübe edildi ve Varian Carry 50 spektrofotometresinde 550 nm’de absorbansları ölçüldü. Nitrit ölçümü için sodyum nitrit (100 mM) ve nitrat ölçümü için potasyum nitrat (80 mM) standart olarak kullanıldı (Nitric Oxide Colorimetric Assay, Cat. No. 1756281 Roche, Mannheim, Germany).

Cilt - Vol. 19 Sayı - No. 4

Malondialdehit ölçümü Malondialdehit (MDA) düzeyleri lipit peroksidasyonu göstergesi olarak spektrofotometrik olarak tiyobarbitürik asit reaksiyonu ile ölçüldü. Yöntemin prensibi MDA’nın barbitürik asitle etkileşerek pembe renk vermesine dayanmaktadır. Oluşan rengin yoğunluğu spektrofotometrik olarak 532 nm’de absorbans olarak ölçüldü. Renkli reaktif 1, 1, 3, 3-tetraetoksipropan primer standart olarak kullanıldı. Yagi’nin yöntemi temel alınarak MDA düzeyleri ölçümü ve hesaplaması yapıldı.[14] Miyeloperoksidaz ölçümü Nötrofil infiltrasyon göstergesi olan MPO O-dianozidine reaksiyonu ile ölçüldü. Yöntemin prensibi indirgenmiş O-diyanozidin’in spektrofotometrik olarak 410 nm’de ölçülmesine dayanmaktadır.[15] Histopatolojik değerlendirme Anastomoz hattını içeren uzunlamasına kalın bağırsak kesitleri bekletilmeden %10’luk formaldehit solüsyonuna konuldu. Patoloji AD laboratuvarına götürülen formaldehit içindeki kesitler burada solüsyon içinde 24 saat tespit edildi. Tespit aşamasından sonra üzerine numara yazılmış olan kasetlere yerleştirildi. Değişen derecelerdeki alkol ve ksilollerden geçirilen dokular 56 °C’ye kadar ısıtılmış parafinde bekletildi. Parafine gömülmüş dokulardan hazırlanan bloklardan mikrotom yardımıyla 5 μ kalınlığında kesitler elde edilerek lamların üzerine alındı. Hazırlanan lamlar deparafinize edilip hematoksilen-eozin boyası ile boyanarak preparatlar hazırlandı. Preparatlar OlyTablo 3. Ehrlich/Hunt skalasına göre anastomoz grupları Grup C D Toplam

Evre 1

Evre 2

Evre 3

Evre 4

0/10 0/10 0/20

1/10 0/10 1/20

6/10 6/10 12/20

3/10 4/10 7/20 307

Ulus Travma Acil Cerrahi Derg

mpus Bx50 ışık mikroskobunda patolog tarafından değerlendirildi. Bağırsak anastomozu iyileşmesini evrelemek için Ehrlich/Hunt’un yara iyileşmesi evreleme sistemi kullanıldı.[16] Bu evreleme sistemine göre anastomoz çevresinde enflamatuvar hücre infiltrasyonu, damar proliferasyonu, fibroblastik proliferasyon ve kollajen birikimi değerlendirildi. 0- Hiç bir parametrenin görülmediği olgular 1- Seyrek enflamatuvar hücre infiltrasyonu içeren olgular, 2- Dağınık enflamatuvar hücre infiltrasyonu, minimal damarlanma artışı ve fibroblastik proliferasyon içeren olgular, 3- Belirgin derecede enflamatuvar hücre infiltrasyonu yoğun damarlanma artışı ve fibroblastik proliferasyon içeren olgular, 4- Enflamatuvar hücre infiltrasyonu ve damar proliferasyonunda azalmayla birlikte yoğun fibroblastik proliferasyon ve kollajen birikimi içeren olgular. İstatistiksel değerlendirme Nitrik oksit, MDA, MPO Hidroksiprolin düzeyi ve patlama basınçları normal dağılım gösterdiğinden tek yönlü varyans analizi (ANOVA) kullanılarak değerlendirildi. Histopatolojik inceleme ve adezyon skorları normal dağılım göstermediği için Kruskall- Wallis test istatistiği ile değerlendirildi. Sıçanlarda oluşan nonparametrik değişkenler (yara enfeksiyonu ve anastomoz kaçağı) Mann-withney U-testi ile değerlendirildi. Nor7 6

10

6

3

4

2

2

1

60

A grubu B grubu

8

4

70

BULGULAR Deneysel çalışmamızda anestezi indüksiyonu esnasında ölen iki sıçan yerine yenileri çalışmaya alındı.

Gruplarda yara enfeksiyonu sıklığı, anastomoz kaçağı sıklığı, adezyon skoru ve biyokimyasal ölçüm sonuçları Tablo 2, Şekil 1 ve Şekil 2’de gösterilmiştir.

Grupların hiçbirinde yara yeri enfeksiyonu görülmedi.

C grubunda bir, D grubunda iki sıçanda anastomoz kaçağı gözlendi. Gruplar arasındaki anastomoz kaçağı farkı istatistiksel olarak anlamlı değildi (p=0,531).

Adezyon skoru A grubunda B grubuna oranla, C grubunda ise D grubuna oranla istatistiksel olarak anlamlı oranda düşük bulundu (p=0,003577, p=0,001612).

Anastomoz yapılan iki grup (C ve D) arasında anastomoz patlama basınçları açısından fark anlamlı değildi (p=0.816). Hidroksiprolin düzeyi A grubunda B grubuna oranla, C grubunda ise D grubuna oranla istatistiksel olarak anlamlı düzeyde yüksek bulundu (p=0,001, p=0,0001). NO düzeyleri açısında A ve B grupları arasındaki fark istatistiksel olarak anlamlı değilken, C grubunda D grubuna oranla istatistiksel olarak anlamlı düzeyde düşük saptandı (p=0,434, 12

A grubu B grubu

5

0

mal dağılanlar için SPSS (ver. 11,5), patoloji değişkeni için ise STATISTICA istatistik paket programı kullanıldı.

Yara inf

Anast kaçağı

Adezyon skoru

0 0.4

A grubu B grubu

Hidroksiprolin

MDA

A grubu B grubu

0.3

50 40

0.2

30 20

0.1

10 0

NO

0

MPO

Şekil 1. A ve B gruplarında deney sonuçları. *Adezyon skoru (p=0,0035), hidroksiprolin (p=0,001), NO (p=0,434), MDA (0,116), MPO (p=0,0001). MDA: Malondialdehit; NO: Nitrik oksit; MPO: Miyeloperoksidaz.

308

Temmuz - July 2013

Karın içi adezyon önleyici %4’lük ikodekstrin solüsyonunun gastrointestinal sistem anastomozları üzerine etkisi 9

164

C grubu D grubu

8 7

162

C grubu D grubu

160

6 5

158

4

156

3

154

2

152

1 0

Yara inf

14

Anast kaçağı

Adezyon skoru

100

C grubu D grubu

12

150

80

10 8

60

6

40

4

Patlama basıncı C grubu D grubu

20

2 0

Hidroksiprolin

0.4 0.35

MDA

0

NO

C grubu D grubu

0.3 0.25 0.2 0.15 0.1 0.05 0

MPO

p=0,001). MDA düzeyleri açısından A ve B grupları arasındaki fark anlamlı değilken, C grubunda D grubuna oranla anlamlı oranda düşük saptandı (p=0,116, p=0,018). MPO değerleri A grubunda B grubuna oranla, C grubunda ise D grubuna oranla anlamlı düzeyde düşük bulundu (p=0,0001, p=0,0001).

Histopatolojik inceleme de Ehrlich/Hunt skalasına göre anastomoz iyileşmesi derecelendirildiğinde bir sıçan evre 2, 12 sıçan evre 3 ve yedi sıçan evre 4 olarak değerlendirildi (Tablo 3, Şekil 3, Şekil 4). Bu derecelendirme sistemine göre C ve D grupları arasında iyileşme evreleri açısından, Kendall’ın tau metodu kullanılarak yapılan karşılaştırmada anlamlı bir farklılık saptanmadı (p=0,462).

Cilt - Vol. 19 Sayı - No. 4

Şekil 2. C ve D gruplarında deney sonuçları.

*Anastomoz kaçağı (p=0,531), adezyon skoru (p=0,0016), patlama basıncı (p=0,816), hidroksiprolin (p=0,0001), NO (p=0,001), MDA (p=0,018), MPO (p=0,0001). MDA: Malondialdehit; NO: Nitrik oksit; MPO: Miyeloperoksidaz.

TARTIŞMA Ameliyat sonrası adezyonları önlemek amacıyla farklı mekanizmalar üzerinden etki eden birçok ajan denenmiştir.[17] Bu etki mekanizmalarından biri periton yüzeyleri arasında mekanik bariyer oluşturmaktır.

Periton hasarı peritonun bütünlüğünü bozan bir travma sonrası gelişir ve adezyonlar travma sonrasındaki beşyedi gün içinde oluşurlar.[18] Kullanılan ajan bu süre boyunca karın içinde varlığını sürdürebilirse periton yüzeylerini birbirinden ayırır. İkodekstrin büyük moleküllü bir ajandır. Periton lenfatiklerinden yavaş emilir. Böylece periton kavitesi içinde uzun süre kalarak hasarlı peritoneal yüzeylerin birbiri ile temasını önler ve adezyonunu engeller.[19] Karın içi adezyonların derecelendirilmesinde çeşitli yöntemler kullanılmakta309

Ulus Travma Acil Cerrahi Derg

azalttığı saptandı.

Literatürde, anastomoz iyileşmesi üzerine yapılmış çok sayıda çalışma vardır. Bu çalışmaların çoğunda anastomoz iyileşmesi anastomoz patlama basıncı, hidroksiprolin düzeyi ve histopatolojik inceleme ile değerlendirilmiştir.[22-26] Genel olarak bu parametrelerin anastomoz iyileşmesini objektif olarak değerlendirdiği yönünde literatürde geniş bir görüş birliği vardır.

Bu nedenle çalışmamızda anastomoz iyileşmesini bu parametrelerle değerlendirdik.

Şekil 3. Ehrlich/Hunt skalasına göre Evre 3 (H-E x 50).

Renkli şekil derginin online sayısında görülebilir (www.tjtes.org).

Anastomoz patlama basıncı, ikodekstrinin anastomozlar üzerine etkisini inceleyen benzer deneysel çalışmalarda anastomoz iyileşmesini değerlendirmek amacıyla kullanılmıştır. Bu çalışmalardan Baca ve arkadaşlarının[7] yaptığı çalışma ile Rodgers ve arkadaşlarının[8] yaptığı çalışmada anastomoz patlama basınçlarını olumsuz yönde etkilemediği belirtilirken, Pascual ve arkadaşlarının[9] yaptığı çalışmada ise ikodekstrinin anastomoz patlama basıncını olumsuz yönde etkilediği bildirilmiştir. Çalışmamızda %4’lük ikodekstrin kullanılan grupla kullanılmayan grup arasında patlama basıncı değerleri açısından istatistiksel olarak anlamlı fark saptanmadı.

Yara/anastomoz iyileşmesini değerlendirmede kullanılan biyokimyasal parametrelerden bir tanesi kollajen miktarı tayinidir. Doku kollajen miktarı bir aminoasit olan hidroksiprolin düzeyinin ölçümü ile saptanır.

Baca ve arkadaşlarının[7] yaptığı çalışmada anastomoz iyileşmesini değerlendirmek amacıyla hidroksiprolin düzeyi ölçülmüş ve ikodekstrin kullanılan grupta daha yüksek hidroksiprolin düzeyi saptanmıştır. Benzeri diğer çalışmalarda ise bu parametre kullanılmamıştır.

[8,9] Çalışmamızda da ikodekstrin kullanılan gruplarda daha yüksek hidroksiprolin düzeyi saptandı.

Şekil 4. Ehrlich/Hunt skalasına göre Evre 4 (H-E x 50).

Renkli şekil derginin online sayısında görülebilir (www.tjtes.org).

dır. Bunlar arasında Links ve arkadaşlarının kullandığı travmatize olmuş alana olan yapışıklık yüzdesine göre yapılan ya da Leach ve arkadaşlarının kullandığı üç ayrı parametreden oluşan sistem sıkça kullanılan yöntemlerdir.[20] Biz çalışmamızda Leach ve arkadaşlarının sistemini kullandık. Bu sistemde adezyonlar tip, yaygınlık, kolay ya da zor ayrılmalarına göre üç ayrı kategoride değerlendirilerek puanlanmaktadır. Literatürde ikodekstrinin adezyon önlemedeki etkinliğini değerlendiren deneysel çalışmalarda farklı sonuçlar bildirilmiştir. Adezyonu azalttığını belirten çalışmalar olduğu gibi başarısız olduğunu belirten çalışmalarda mevcuttur.[2-6] Müller ve arkadaşlarının[21] yaptığı çalışmada ise peritonitli olgularda yapışıklığı azaltmadığı gibi daha sık apse gelişimine neden olduğu bildirilmiştir. Çalışmamızda ise sonuçlar değerlendirildiğinde ikodekstrinin yapışıklık oluşumunu belirgin olarak 310

Yara/anastomoz iyileşmesininin histopatolojik olarak değerlendirilmesinde evreleme için kullanılan yöntemlerden biri Ehrlich/Hunt’un yara iyileşmesi evreleme sistemidir.[16] Bu evreleme sisteminde anastomoz çevresinde enflamatuvar hücre infiltrasyonu, damar proliferasyonu, fibroblastik proliferasyon ve kollajen birikimine göre anastomozlar 0 ile 4 arasında derecelendirilmektedir. Çalışmamızda bu evreleme sistemi kullanıldı. İkodekstrinin anastomoz iyileşmesine etkisini inceleyen çalışmalardan Rodgers ve arkadaşlarının yaptığı çalışma ile Baca ve arkadaşlarının yaptığı çalışmada histopatolojik inceleme sonuçlarına göre anastomoz iyileşmesini olumsuz yönde etkilemediği belirtilmiştir.[7,8] Çalışmamızda da %4’lük ikodekstrin kullanılan ve kullanılmayan grup arasında anastomoz iyileşmesinde anlamlı farklılık saptanmadı.

Nitrik oksit, MDA ve MPO enflamatuvar hücrelerce üretilen ya da yan ürün olarak oluşan maddelerdir.

NO Nötrofillerde bulunan İNOS (İndüklenebilir Nitrikoksit Sentetaz) enzimi aracılığıyla üretilir. Sepsis Temmuz - July 2013

Karın içi adezyon önleyici %4’lük ikodekstrin solüsyonunun gastrointestinal sistem anastomozları üzerine etkisi

ve inflamasyonda İNOS enziminin tetiklenmesi sonucunda NO üretimi artar.[27,28] Çalışmamızda anastomoz yapılmayan gruplar arasında NO düzeyleri arasında fark olmadığı saptandı. Anastomoz yapılan gruplarda ise ikodekstrin kullanılan grupta kullanılmayan gruba göre NO düzeyi anlamlı düzeyde düşüktü. MDA enflamatuvar yanıtta görevli hücreler tarafından üretilen oksijen radikallerinin plazma ve hücre mebranları gibi lipit içeren yapıları parçalamasıyla oluşan bir yan üründür. Hem doku hasarı hemde enflamasyon şiddetinin değerlendirilmesinde kullanılan bir parametredir.

[29,30] Çalışmamızda anastomoz yapılmayan gruplar arasında MDA düzeyleri açısından anlamlı fark yoktu.

Anastomoz yapılan gruplarda ise %4’lük ikodekstrin kullanılan grupta MDA düzeyinin anlamlı miktarda düşük olduğu saptandı. Anastomoz yapılmayan gruplarda NO ve MDA düzeyindeki düşüklüğün sebebi oluşturulan çekum abrazyonunun düşük düzeyde bir periton hasarına yol açmış olması ve düşük derecede bir enflamatuvar yanıt oluşması olabilir. Anastomoz yapılan gruplarda NO ve MDA düzeylerinin düşük saptanması ise daha düşük şiddette bir enflamatuvar yanıt, dolayısıyla daha az adezyon ve doku hasarı oluştuğunun göstergesidir. MPO nötrofillerin fagozite ettikleri ajanları parçalaması amacıyla kullandıkları toksik ajanların oluşturulmasında kullanılan bir enzimdir. Dokularda nötrofil infiltrasyonunun göstergesi olarak kullanılır. Çalışmamızda anastomoz yapılmayan iki grup arasında %4’lük ikodekstrin kullanılan grupta MPO düzeyinin anlamlı düzeyde düşük olduğu saptandı (p=0,0001). Anastomoz yapılan gruplar arasında da %4’lük ikodekstrin kullanılan grupta MPO anlamlı düzeyde daha düşüktü (p=0,0001). Bu değerin düşük saptanması daha düşük şiddetli bir enflamatuvar yanıt dolayısıyla daha az adezyon oluştuğunun göstergesidir. Literatürde bu parametreleri değerlendiren benzer çalışma bulunamamıştır. Çalışmamızda elde edilen biyokimyasal ve mekanik parametreler adezyon önleyici ajan olarak kullandığımız %4’lük ikodekstrin solüsyonunun karın içi adezyonları önlemede etkin olduğunu ve anastomoz iyileşmesini olumsuz yönde etkilemediğini düşündürmektedir.

Yazar(lar) ya da yazı ile ilgili bildirilen herhangi bir ilgi çakışması yoktur.

KAYNAKLAR 1. Saribeyoğlu K, Pekmezci S, Korman U, Kol E, Baca B, Günay S. Selective laparoscopic adhesiolysis in the management of acute and chronic recurrent adhesive bowel obstruction. Ulus Travma Acil Cerrahi Derg 2008;14:28-33.

2. Ditzel M, Deerenberg EB, Komen N, Mulder IM, Jeekel H, Lange JF. Postoperative adhesion prevention with a new barrier: an experimental study. Eur Surg Res 2012;48:187-93.

3. Lang RA, Grüntzig PM, Weisgerber C, Weis C, Odermatt EK, Kirschner MH. Polyvinyl alcohol gel prevents abdominal adhesion formation in a rabbit model. Fertil Steril Cilt - Vol. 19 Sayı - No. 4

2007;88:1180-6.

4. Müller SA, Treutner KH, Anurov M, Titkova S, Oettinger AP, Schumpelick V. Experimental evaluation of phospholipids and icodextrin in re-formation of peritoneal adhesions. Br J Surg 2003;90:1604-7.

5. Verco SJ, Peers EM, Brown CB, Rodgers KE, Roda N, diZerega G. Development of a novel glucose polymer solution (icodextrin) for adhesion prevention: pre-clinical studies.

Hum Reprod 2000;15:1764-72.

6. Tepetes K, Asprodini EK, Christodoulidis G, Spyridakis M, Kouvaras E, Hatzitheofilou K. Prevention of postoperative adhesion formation by individual and combined administration of 4 per cent icodextrin and dimetindene maleate. Br J Surg 2009;96:1476-83.

7. Baca B, Boler DE, Onur E, Akca O, Hamzaoglu I, Karahasanoglu T, et al. Icodextrin and Seprafilm do not interfere with colonic anastomosis in rats. Eur Surg Res 2007;39:318-23.

8. Rodgers KE, Verco SJ, diZerega GS. Effects of intraperitoneal 4% icodextrin solution on the healing of bowel anastomoses and laparotomy incisions in rabbits. Colorectal Dis 2003;5:324-30.

9. Pascual I, Fernández de Miguel G, García Arranz M, GarcíaOlmo D. Biosutures improve healing of experimental weak colonic anastomoses. Int J Colorectal Dis 2010;25:144751.

10. Dijkstra FR, Nieuwenhuijzen M, Reijnen MM, van Goor H. Recent clinical developments in pathophysiology, epidemiology, diagnosis and treatment of intra-abdominal adhesions.

Scand J Gastroenterol Suppl 2000;232:52-9.

11. Olfert ED, Cross BM, McWilliam AA. Guide to the care and use of experimental animals. Canada, Canadian Council on Animal Care 1993;1-298.

12. Bergman I, Loxly R. Two impaired and simplified methods for the spectro-photometric determination of hydroxyproline.

Ann Chem 1963;35:1961-5.

13. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982;126:131-8.

14. Yagi K. Simple procedure for specific assay of lipid hydroperoxides in serum or plasma. Methods Mol Biol 1998;108:10710.

15. Golowich SP, Kaplan SD. Methods in enzymology. Vol. 2., New York: Aca Press Inc.; 1955. p. 769.

16. Ehrlich HP, Tarver H, Hunt TK. Effects of vitamin A and glucocorticoids upon inflammation and collagen synthesis. Ann Surg 1973;177:222-7.

17. Ellis H. The causes and prevention of intestinal adhesions. Br J Surg 1982;69:241-3.

18. Holmdahl L, Risberg B, Beck DE, Burns JW, Chegini N, diZerega GS, et al. Adhesions: pathogenesis and preventionpanel discussion and summary. Eur J Surg Suppl 1997;577:5662.

19. Başak F. In the experimental adhesion model, effect of viscosities of the fluids that are added into the peritoneal cavity on preventing peritoneal adhesions. [Thesis of medical specialty] Istanbul: Ministry of Health Clinic in Istanbul Training and Research Hospital; 2007.

20. Fazli D, Hakan A, Ahmet CC. Comparison of the adhesion scoring systems used in animal models and assessment of interobserver reproducibility. Australian and New Zealand Journal of Obstetrics and Gynaecology 2006;46:356-9.

21. Müller SA, Treutner KH, Haase G, Kinzel S, Tietze L, Schumpelick V. Effect of intraperitoneal antiadhesive fluids in a rat peritonitis model. Arch Surg 2003;138:286-90.

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22. Hesp FL, Hendriks T, Lubbers EJ, deBoer HH. Wound healing in the intestinal wall. A comparison between experimental ileal and colonic anastomoses. Dis Colon Rectum 1984;27:99-104.

23. Irvin TT, Hunt TK. Reappraisal of the healing process of anastomosis of the colon. Surg Gynecol Obstet 1974;138:741-6.

24. Jiborn H, Ahonen J, Zederfeldt B. Healing of experimental colonic anastomoses. I. Bursting strength of the colon after left colon resection and anastomosis. Am J Surg 1978;136:58794.

25. Kuzu MA, Kรถksoy C, Kale IT, Tanik A, Terzi C, Elhan AH. Reperfusion injury delays healing of intestinal anastomosis in a rat. Am J Surg 1998;176:348-51.

26. Colak T, Nayci A, Polat G, Polat A, Comelekoglu U, Kanik A, Turkmenoglu O, Aydin S. Effects of trapidil on the healing

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of colonic anastomoses in an experimental rat model. ANZ J Surg 2003;73:916-21.

27. Anup R, Balasubramanian KA. Surgical stress and the gastrointestinal tract. J Surg Res 2000;92:291-300.

28. Faist E, Schinkel C, Zimmer S. Update on the mechanisms of immune suppression of injury and immune modulation.

World J Surg 1996;20:454-9.

29. Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK. Free radicals and the heart. J Pharmacol Toxicol Methods 1993;30:55-67.

30. Singal PK, Beamish RE, Dhalla NS. Potential oxidative pathways of catecholamines in the formation of lipid peroxides and genesis of heart disease. Adv Exp Med Biol 1983;161:391-401.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):313-319

Experimental Study

Deneysel Çalışma doi: 10.5505/tjtes.2013.45804

Effects of combined and individual use of N-methyl-D aspartate receptor antagonist magnesium sulphate and caspase-9 inhibitor z-LEDH-fmk in experimental spinal cord injury Sıçanlarda oluşturulan deneysel omurilik yaralanmasında N-metil D-aspartat reseptör antagonisti olan magnezyum sülfat ve kaspaz-9 inhibitörü olan z-LEDH-fmk’nın tek başına ve kombine kullanımlarındaki etkinliklerinin karşılaştırılması Altay SENCER,1 Aydın AYDOSELİ,1 Yavuz ARAS,1 Mehmet Osman AKÇAKAYA,1 Cengiz GÖMLEKSİZ,2 Halil CAN,3 Ali CANBOLAT1 BACKGROUND

AMAÇ

We investigated the individual and combined effects of magnesium sulphate, which is an N-Methyl-D aspartate receptor antagonist (NMDA), and z-LEHD-FMK, which is a caspase 9 inhibitor, on the genesis of secondary injury in a rat spinal cord injury model. We aimed to minimize the effects of secondary injury in spinal cord trauma by choosing these two agents which served to block the two major mechanisms of cell loss, apoptosis and necrosis.

Sıçanlarda oluşturulan omurilik travması sonrasında bir N-metil D-aspartat (NMDA) reseptör antagonisti olan magnezyum sülfat’ın ve kaspaz-9 inhibitörü olan z-LEHDFMK’nın ikincil hasar gelişimi üzerine olan etkileri karşılaştırıldı. Apoptozis ve nekrozun omurilik travması sonrası hasar görmüş hücrelerin kaybedilmesindeki iki ana yolu teşkil etmelerini göz önüne alarak kullandığımız bu iki ajan ile ikincil hasarın iki ana mekanizmasını birlikte engelleyerek ikincil hasarı en aza indirmeyi hedefledik.

METHODS

GEREÇ VE YÖNTEM

The drugs were given to the subjects according to their groups, either in singular or combined fashion. For motor examination, the subjects were kept under close clinical evaluation for five days. Histopathological examination and the emerging spinal cord samples were prepared with haematoxylene-eosin and Tunel techniques.

Omurilik travması sonrası deneklere gruplarına göre, ayrı ayrı ve kombine olarak, ilaç tedavisi uygulandı. Denekler beş gün boyunca klinik olarak gözlendi ve nörolojik fonksiyonları kaydedildi. Histopatolojik değerlendirme için beşinci gün sonunda alınan omurilik örnekleri hematoksilen eozin ve Tunel yöntemi ile boyanarak mikroskobik olarak incelendi.

RESULTS

BULGULAR

A statistically significant difference in favor of the treatment groups has been found between the treatment and control groups in terms of histological data. However, there was no difference in the evaluation of motor examination between trauma and treatment groups.

CONCLUSION

We have found no difference between the individual and combined uses of MgSO4 and z-LEHD-FMK in the prevention of secondary injury; however, there were better histological results in the treatment groups compared to trauma and control groups which gives us hope for future investigations.

Key Words: Apoptosis; magnesium sulphate; necrosis; neuroprotection; spinal cord injury; z-LEDH-FMK. Department of Neurosurgery, IU Istanbul Faculty of Medicine, Istanbul; 2 Department of Neurosurgery, Erzincan University Faculty of Medicine, Erzincan; 3Department of Neurosurgery, Medicine Hospital Asia, Istanbul, Turkey.

1

Elde edilen verilerin karşılaştırılmasında, tedavi grupları ile kontrol grupları arasında histopatolojik açıdan tedavi grupları lehine istatistiksel olarak anlamlı fark bulundu, ancak motor inceleme bulgularının değerlendirmesinde travma ve tedavi grupları arasında anlamlı bir farklılık yoktu.

SONUÇ

İkincil hasar gelişiminin önlenmesinde MgSO4 ve z-LEHDFMK’nın kombine kullanımı ile izole kullanımları arasında istatistiksel olarak anlamlı bir fark bulunmamış, ancak tedavi grupları travma ve kontrol gruplarından daha iyi sonuçlara sahip olduğu görülmüş ve bu da omurilik travmasının gelecekteki tedavisi açısından umut verici bulunmuştur.

Anahtar Sözcükler: Apoptozis; magnezyum sülfat; nekroz; omurilik yaralanması; sinir dokusunun korunması; z-LEDH-FMK. İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, İstanbul; 2Erzincan Üniversitesi Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Erzincan; 3 Medicine Hospital Asya, Beyin ve Sinir Cerrahisi Bölümü, İstanbul.

1

Correspondence (İletişim): Mehmet Osman Akçakaya, M.D. İstanbul Üniversitesi Tıp Fakültesi, Nöroşirürji Anabilim Dalı, 6. Kat, Çapa, 34340 İstanbul, Turkey.

Tel: +90 - 212 - 414 20 00 / 32399 e-mail (e-posta): moakcakaya@gmail.com

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Until the last decade, necrosis has been accepted as the only mechanism for cell death in tissue damage following spinal cord injury (SCI). However, recent publications have also indicated the importance of apoptotic cell death after SCI.[1-4] Unlike necrosis, apoptosis is a “programmed cell death” mechanism, where the cells are autodigested by enzymatic reactions and then removed by phagocytes without an inflammatory response. Caspases, formerly known as cysteine proteases, are the key regulators of apoptosis.

[4-7] Various caspases and apoptotic cascades induced by caspase-dependent signaling have been described.

There are several studies demonstrating promising results for preventing secondary injury in SCI with inhibition of apoptosis.[3,8-13] Caspase-9 is a key initiator of apoptosis, which activates the mitochondria-mediated pathway (intrinsic pathway).[14] z-LEDH-fmk is a selective, irreversible caspase-9 inhibitor that has been found to be effective as an antiapoptotic agent in animal models of cerebral ischemia and SCI.[15,16]

ketamine hydrochloride (Parke-Dewis, Eczacıbası, Istanbul, Turkey). The rats were placed in prone position. Body temperature of the rats was kept constant using a heating lamp at 37 ºC monitored with a rectal temperature probe. After shaving the dorsal region of each rat and scrubbing with povidine iodine solution (Adeka, Samsun, Turkey) a dorsal midline skin incision was performed (Figure 2). Following dissection of paravertebral muscles (Figure 3), middorsal two level (approximately T7-9) laminectomies and bilateral facetectomies were performed (Figure 4). The transverse processes were also removed in order to apply the aneurysm clip vertically to the spinal cord axis (Figure 5). The dura mater was left intact. After surgical interventions the wound was closed in layers with 3/0 atraumatic silk sutures.

Various reports demonstrated the effects of antiapoptotic caspase inhibitors and magnesium treatment in SCI separately. However, there is no research on the combined inhibition of these two major pathways of secondary injury. In this study we investigated the individual and combined effects of MgSO4, which is a NMDA receptor antagonist, and z-LEDH-fmk, which is a caspase-9 inhibitor, on the trauma-induced secondary injury in a rat SCI model acquired by static compression technique. The aim was to demonstrate the inhibitory effects on secondary injury of these two agents that block the two major mechanisms of cell loss: apoptosis and necrosis.

• Group 1 (Sham-Operated Controls): Only laminectomies (n=9).

MATERIALS AND METHODS In the study, 54 male Sprague-Dawley rats obtained from the Research Center for Experimental Medicine were used. The animals, weighing 280-340 g and aged 10-12 months were fed a normal diet during the study period and housed under diurnal light conditions. All experimental protocols were approved by the local institutional animal care and use committee and institutional ethical committees of Istanbul University.

Traumatic injury model The SCI was produced by acute spinal cord compression technique described by Rivlin and Tator.[17] The rats were injured using Yaşargil FE 716 K (with a closing force of 110 g, Aesculap/Germany) aneurysm clips which produce a compression force of 110 g with 30 seconds of compression duration.

Surgical procedure The surgical procedure was performed under general anesthesia after intraperitoneal injection of 9 mg/ kg xylasine (Bayer, Istanbul, Turkey) and 60 mg/kg 314

Treatment groups The rats were randomly and blindly divided into the following six groups each consisting of 9 animals:

• Group 2 (Trauma-Only Controls): Laminectomy and SCI (n=9).

• Group 3 (Placebo Controls): After laminectomy and SCI rats were treated with intraperitoneally-injected physiological serum (0.9% NaCl) immediately after procedure and daily for the following five days (n=9).

• Group 4 (Trauma and MgSO4 Treatment Group): Laminectomy and SCI performed. A single dose of 100 mg/kg of MgSO4 (Biofarma, Istanbul, Turkey) was administered intraperitoneally immediately after the procedure and daily for the following five days (n=9).

• Group 5 (Trauma and Combined Treatment Group): Following laminectomy and SCI, the rats were treated with combination therapy of intraperitoneally-injected 100 mg/kg of MgSO4 (Biofarma, Istanbul, Turkey) and 0.6 umol/kg of z-LEHD-fmk (Calbiochem GmGH, Kimeks, Istanbul, Turkey) immediately after the procedure and daily for the following five days. The dry form of z-LEHD-fmk was diluted in physiological serum.

• Group 6 (Trauma and z-LEHD-fmk Treatment Group): Following laminectomy and SCI, the rats were treated with intraperitoneally-injected 0.6 μmol/ kg of z-LEHD-fmk (Calbiochem GmGH, Kimeks, Istanbul, Turkey) immediately after the procedure and daily for the following five days.

The animals were followed-up for five days after the surgical procedure. Functional assessments were performed on the first, third, and fifth days postoperatively. The animals were reanesthetized on the fifth day as described above and then killed with intracarTemmuz - July 2013

Individual and combined use of MGSO4 and z-LEDH-fmk in spinal cord injury

(a)

(b)

Fig. 1. (a) Photomicrograph shows a specimen from trauma-only group prepared with TUNEL technique, indicating the increased number of brown coloured apoptotic cells. (b) H&E staining of the same specimen shows increased number of cavitation areas. (Color figur can be viewed in the online issue, which is available at www.tjtes.org).

diac injection of 2cc KCl solution. The animals were then placed in prone position. The skin was reopened and samples from the laminectomized spinal cord were taken using a longitudinal dural incision. The specimens were fixed in 0.1 mol phosphate-buffered 2.5% glutaraldehyde solution.

Functional assessment Neurological function of each rat was evaluated with the objective “inclined-plane technique” on the first, third, and fifth days after the surgical procedure.

[18] The subjective “Tarlov motor grading scale” was also used to assess functional recovery.[19] The assessments were performed by investigators who were blind to procedures.

Histological studies The specimens obtained on the fifth day postoperatively were prepared for histological investigation.

Hematoxylin and eosin (H&E) staining and TUNEL staining were used for histological assessment. For H&E staining, samples were fixed in 0.1 mol phosphate-buffered 2.5% glutaraldehyde solution and embedded in parafin. 5 μm-thick sections were cut and stained with H&E. For TUNEL staining, samples were prepared according to the TUNEL technique,[20] which enables counting of apoptotic cells. The specimens were obtained as close as possible from the center of the lesion site. 5 μm-thick sections were cut and stained with the TUNEL technique. The samples were examined with Olympus Bx50 light microscope at magnification level of 20x.

A blinded investigator not involved in the procedures counted the number of the apoptotic cells in these sections. The percentage of the apoptotic cells among all cells were recorded and classified as follows: 0-25%, 25-50%, 50-75% and 75-100%. The Cilt - Vol. 19 Sayı - No. 4

number of the lymphocytes and polymorpho nuclear leukocytes (PNL) and their percentage among the inflammatory cells in these sections were recorded as an indicator of the inflammatory response. Cavitation areas in the sections were assessed as a sign of necrosis; the number of cavitation areas was also recorded and quantified as a percentage.

Statistical analysis All the data were analyzed with Kruskal-Wallis variance analysis and Mann-Whitney U-test except the parametric data from the motor evaluation with inclined-plane technique. Parametric data were analyzed with ANOVA variance analysis and Scheffe test for multiple comparisons. All results are based on twosided tests for p=0.05.

Fig. 2. Photomicrograph shows a specimen from combined treatment group prepared with TUNEL technique.

A significant decrease is observed in the number of apoptotic cells.

(Color figur can be viewed in the online issue, which is available at www.tjtes.org).

315

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RESULTS Functional findings There was a statistically significant difference between the sham-operated control and trauma groups in the means of inclined-plane scores (p<0.001). Trauma caused a significant decrease in inclined-plane scores as expected. The results obtained in the trauma-only and placebo groups were significantly different from those in the treatment groups, but there were no significant differences between these two groups. All three treatment modalities caused increases in inclinedplane scores. The z-LEDH-fmk and combined treatment groups showed a significant increase in inclinedplane scores compared to MgSO4 group. There was no statistically significant difference between z-LEDHfmk and combined treatment groups.

Functional assessment using “Tarlov motor grading scale” resulted in no statistically significant difference among all the trauma groups, except significantly better results for sham-operated control group.

The results for functional assessment are summarized in Table 1 and Table 2.

Histological findings There was a significant difference in the means of lymphocytes and PNL counts and percentages in sham-operated control group compared to traumaonly and placebo groups. As expected there were no lymphocytes or PNL in the control groups. Traumaonly and placebo groups showed significantly worse results than the combined and z-LEDH-fmk treatment groups. There was no significant difference between the three treatment groups, although the percentage of lymphocyte and PNL was lower in the combined treatment group compared to the other two treatment groups (p<0.001). The presence of necrosis was assessed and no significant difference was found between all groups (p<0.002).

The results for TUNEL staining and apoptotic cell counts revealed a significant difference in the shamoperated group compared to trauma-only and placebo groups. These two groups showed significantly worse results compared to the combined and z-LEDH-fmk groups. There was no significant difference between the treatment groups (p<0.001).

The results for histological assessment are summarized in Table 3, Table 4, and Table 5.

DISCUSSION Despite many efforts, SCI still has no definite cure and continues to be a serious medical threat to the patient as well as a burden on the patient’s family and the state economy. The fact that 61% of patients are between 16-30 further contributes to the graveness of the problem.[21] 316

Table 1. Distribution of Tarlov Motor Grading scores in six experiment groups Tarlov Motor Grading

Day 1

Day 3

Day 5

5 1 1 1 1 1 53

5 1 1 1 1 1 49

5 1 1 1 1 1 40.48

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 KW-χ2

Table 2. Summary of inclined plane results for the six groups of rats Inclined plane

Day 1

Day 3

Day 5

(degree)

Mean±SD

Mean±SD

Mean±SD

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6

42.33±0.50 28.77±1.20 27.77±0.97 30.89±1.61 33.00±0.71 32.77±0.66

42.55±0.53 28.33±1.32 27.89±0.33 30.67±1.58 34.00±0.71 33.33±0.50

43.00±0.00 28.78±1.20 28.00±0.86 30.77±1.20 34.33±0.71 33.55±0.72

Table 3. PNL and Lymphocytes counts as percentage

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 KW-χ2

PNL (%)

Lymphocyte (%)

0 100 100 55.6 11.1 22.2 34.65

0 100 100 55.6 11.1 22.2 34.65

PNL: Polymorpho nuclear leukocytes.

Primary and secondary injuries following the trauma result in tissue damage. Direct mechanical damage to neurovascular structures is called primary injury, which has no treatment by primary health care measures other than prevention. After the primary injury, the initially-intact, surrounding neural tissue is also attacked by various molecular pathways. This delayed tissue damage is called secondary injury. Preventing secondary injury by modulating different molecular mechanisms has become the focus of numerous investigations.[22-25] Currently there is no definitive treatment for secondary injury in SCI, despite the common use of corticosteroids, which are expected to prevent secondary injury through several mechanisms.[26] Traumatic SCI results in acute mechanical damage and ischemia and leads to neural tissue degeneration.

Necrosis is accepted as the main mechanism causing cell death.[27] Excitotoxicity has been assumed to be the Temmuz - July 2013

Individual and combined use of MGSO4 and z-LEDH-fmk in spinal cord injury

Table 4. The presence of necrosis in six experimental groups as percentage

Necrosis

– (%)

+ (%)

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 KW-χ2

100 44.4 33.3 55.6 88.9 100 18.48

0 55.6 66.7 44.4 11.1 0 –

Table 5. The presence apoptosis in six groups of rats

Apoptosis (%)

0-25

25-50

50-75

75-100

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6

100 0 0 66.7 88.9 77.8

0 33.3 33.3 11.1 11.1 22.2

0 44.4 55.6 22.2 0 0

0 22.2 11.1 0 0 0

KW-χ2

37.02

key factor in necrosis and neuronal degeneration.[23,28] Excitatory neurotransmitters, especially glutamate, the primary neurotransmitter in the spinal cord, play a crucial role by causing neurotoxicity in conditions like spinal cord ischemia or SCI where the cellular energy levels are decreased. The prevention of secondary injury after SCI with the use of N-methyl-D-aspartate (NMDA) receptor antagonists is well studied.

There is limited but promising research on the use of magnesium sulphate (MgSO4) in SCI.[29-34] MgSO4 is an NMDA receptor antagonist, which has been used clinically as a neuroprotective agent for treating acute stroke and other conditions like preeclampsia, atrial fibrillation, myocardial infarction 29 and experimentally in animal models of brain injury.[35-37] Recent studies have demonstrated that necrosis is not the only mechanism in cell death; apoptosis also has a major role in this process.[38-40] Because apoptosis needs energy, heavily injured cells die via necrosis, but the surrounding mildly damaged neural tissue can lose cells via apoptosis. Investigations focused on regulating apoptosis with new drug therapies in order to protect neural tissue and motor function.[41] MgSO4 is a well-known NMDA receptor blocker that has a neuroproctective effect in neural tissue through glutamate antagonism and reduction of excitotoxicity.[24,36,42] Additionally, its antiapoptotic effect through caspase 3 inhibition has been shown in Cilt - Vol. 19 Sayı - No. 4

an animal model of hipoxic-ischemic brain injury.[43] This agent is still widely used in clinical practice for the treatment of conditions like preeclampsia, atrial fibrillation, stroke, myocardial infarction and vasospasm following subarachnoid hemorrhage (SAH).

In a controlled clinical trial done by van den Bergh et al., MgSO4 was shown to reduce delayed cerebral ischemia following SAH significantly.[44] Wong et al. demonstrated the reduction of symptomatic vasospasm after SAH in a prospective randomized trial.

[45] Solaroglu et al. have shown the inhibitor effect of MgSO4 on necrosis and apoptosis through caspase 3 blockage in SCI.[33] However, experimental and clinical studies on the effects of MgSO4 on secondary injury in SCI are limited.[24,30] Our study revealed that with MgSO4 use, better histological results were achieved, such as reduced number of inflammatory cells and reduced necrosis and apoptosis, which may indicate effective inhibition of secondary injury. Although MgSO4 has the ability to block both major pathways of secondary injury, namely necrosis through NMDA receptor inhibition and apoptosis through caspase 3 inhibition, no statistically significant difference was found among MgSO4, z-LEDH-fmk and combined treatment groups in the current study. Despite the lack of statistical significance, histological results was found to be better in zLEDH-fmk and combined treatment groups with less inflammatory cells and reduced necrosis and apoptosis compared to MgSO4 treatment group. We believe further research is necessary to assess the therapeutic effect of MgSO4 after SCI. Caspases play an important role in apoptosis.

Caspase 9 is the key initiator of the cytochrome-c dependent apoptosis. Brown et al.[46] demonstrated that caspase inhibition in cytokine deprived hematopoetic cells and blocks cell death. Kaptanoglu et al investigated inhibition of caspase 3 activation with mexiletine treatment and achieved better neurological results compared to metilprednisolon treatment.

[47] z-LEDH-fmk is a selective, irreversible, potent caspase 9 inhibitor with known antiapoptotic effect.

[15,16] Mouw et al. demonstrated better neurological results with the use of z-LEDH-fmk in a reversible focal cerebral ischemia model.[7] In a different investigation z-LEDH-fmk is proven to reduce lymphocyte apoptosis in a polimicrobial sepsis model in rats.[48] Colak et al. reported the effective inhibition of apoptosis with z-LEDHfmk in an animal model of SCI.[9] The combined use of MgSO4 and z-LEDH-fmk was evaluated in the literature and there were no obvious complications or toxicity recorded due to combined treatment. Histological findings were significantly better in all treatment groups when comparing trauma to placebo groups. There were no significant 317

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differences between the treatment groups. The percentage of lymphocytes and PNL was the lowest in the combined treatment group followed by z-LEDHfmk and MgSO4 treatment groups. The percentage of apoptotic cells was found to be the lowest in the combined treatment group. However necrosis was found to be the lowest in z-LEDH-fmk treatment group, followed by the combined and MgSO4 treatment groups.

Though there was no significant difference, the acute inflammatory response and apoptosis seemed to be reduced with the combined use of these two agents. The percentage of acute inflammatory and apoptotic cells was the lowest in this group, followed by z-LEDHfmk and MgSO4 alone.

Inclined-plane test revealed better results for the comparison of treatment groups to the trauma and placebo groups. The combined and z-LEDH-fmk groups showed significantly better results compared to MgSO4 group. Among the three treatment modalities, the most unfavorable results were achieved in MgSO4 group. However, no statistically significant difference was found between the combined and zLEDH-fmk groups. There were no significant differences in the means of motor evaluation between all groups. Compared to similar studies in the literature, our study revealed no success regarding neurological function. Maybe there is an association with the selected trauma model. In most of the recent studies the weight-drop technique was used, whereas in our study clip-compression method was used. Weightdrop method was criticized because of the difficulty to standardize the trauma.[15,49] The motor grading scales were low for all groups (1.0) except the sham-operated group and remained the same for the rest of the study, although there were progress in inclined-plane scores.

Tail movement lasted for 3-4 seconds 13 seconds after the clip was applied, then the tail remained atonic indicating paraplegia. These relatively subjective test results were better in most other studies, even in trauma groups without treatment. The reason for the unfavorable motor grading scale results may be caused by the short follow-up period of this study.

In this study, we demonstrated that the individual and combined use of MgSO4 and z-LEDH-fmk could achieve better histological and functional results. Although there was no statistically significant difference found between the treatment groups in histological evaluation, combined use showed better histological results compared to the individual use, which gives us hope for future investigations. This combination blocks necrosis and apoptosis, two main pathways leading to secondary injury following SCI. Further invivo and in-vitro investigations should be planned in order to create a new potential combined therapy for patients with SCI. 318

Conflict-of-interest issues regarding the authorship or article: None declared.

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7. Mouw G, Zechel JL, Zhou Y, Lust WD, Selman WR, Ratcheson RA. Caspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia.

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8. Akdemir O, Uçankale M, Karaoğlan A, Barut S, Sağmanligil A, Bilguvar K, et al. Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury. J Clin Neurosci 2008;15:1130-6.

9. Colak A, Karaoğlan A, Barut S, Köktürk S, Akyildiz AI, Taşyürekli M. Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury. J Neurosurg Spine 2005;2:327-34.

10. Colak A, Antar V, Karaoğlan A, Akdemir O, Sahan E, Celik O, et al. Q-VD-OPh, a pancaspase inhibitor, reduces traumainduced apoptosis and improves the recovery of hind-limb function in rats after spinal cord injury. Neurocirugia (Astur) 2009;20:533-40.

11. Keane RW, Kraydieh S, Lotocki G, Bethea JR, Krajewski S, Reed JC, et al. Apoptotic and anti-apoptotic mechanisms following spinal cord injury. J Neuropathol Exp Neurol 2001;60:422-9.

12. Sîrbulescu RF, Zupanc GK. Inhibition of caspase-3-mediated apoptosis improves spinal cord repair in a regeneration-competent vertebrate system. Neuroscience 2010;171:599-612.

13. Sugawara T, Lewén A, Gasche Y, Yu F, Chan PH. Overexpression of SOD1 protects vulnerable motor neurons after spinal cord injury by attenuating mitochondrial cytochrome c release. FASEB J 2002;16:1997-9.

14. Zheng TS, Flavell RA. Divinations and surprises: genetic analysis of caspase function in mice. Exp Cell Res 2000;256:67-73.

15. de la Torre JC. Spinal cord injury models. Prog Neurobiol 1984;22:289-344.

16. Rudel T. Caspase inhibitors in prevention of apoptosis. Herz 1999;24:236-41.

17. Rivlin AS, Tator CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Temmuz - July 2013

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Neurol 1978;10:38-43.

18. Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in the rat. J Neurosurg 1977;47:577-81.

19. Tarlov IM. Spinal cord compression: Mechanism of paralysis and treatment. Springfield, Illinois: Thomas CC; 1957.

20. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992;119:493-501.

21. Schwab ME, Bartholdi D. Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 1996;76:31970.

22. Anderson DK, Hall ED. Pathophysiology of spinal cord trauma. Ann Emerg Med 1993;22:987-92.

23. Dumont RJ, Verma S, Okonkwo DO, Hurlbert RJ, Boulos PT, Ellegala DB, et al. Acute spinal cord injury, part II: contemporary pharmacotherapy. Clin Neuropharmacol 2001;24:265-79.

24. Kaptanoglu E, Beskonakli E, Okutan O, Selcuk Surucu H, Taskin Y. Effect of magnesium sulphate in experimental spinal cord injury: evaluation with ultrastructural findings and early clinical results. J Clin Neurosci 2003;10:329-34.

25. Tator CH. Update on the pathophysiology and pathology of acute spinal cord injury. Brain Pathol 1995;5:407-13.

26. Braughler JM, Hall ED. Current application of “high-dose” steroid therapy for CNS injury. A pharmacological perspective. J Neurosurg 1985;62:806-10.

27. Zhang Z, Krebs CJ, Guth L. Experimental analysis of progressive necrosis after spinal cord trauma in the rat: etiological role of the inflammatory response. Exp Neurol 1997;143:141-52.

28. Li S, Stys PK. Mechanisms of ionotropic glutamate receptormediated excitotoxicity in isolated spinal cord white matter.

J Neurosci 2000;20:1190-8.

29. Jellish WS, Zhang X, Langen KE, Spector MS, Scalfani MT, White FA. Intrathecal magnesium sulfate administration at the time of experimental ischemia improves neurological functioning by reducing acute and delayed loss of motor neurons in the spinal cord. Anesthesiology 2008;108:78-86.

30. Kaptanoglu E, Beskonakli E, Solaroglu I, Kilinc A, Taskin Y. Magnesium sulfate treatment in experimental spinal cord injury: emphasis on vascular changes and early clinical results.

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32. Saeki H, Matsumoto M, Kaneko S, Tsuruta S, Cui YJ, Ohtake K, et al. Is intrathecal magnesium sulfate safe and protective against ischemic spinal cord injury in rabbits? Anesth Analg 2004;99:1805-12.

33. Solaroglu I, Kaptanoglu E, Okutan O, Beskonakli E, Attar A, Kilinc K. Magnesium sulfate treatment decreases caspase-3 activity after experimental spinal cord injury in rats. Surg Neurol 2005;64:17-21.

34. Süzer T, Coskun E, Islekel H, Tahta K. Neuroprotective effect of magnesium on lipid peroxidation and axonal func-

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tion after experimental spinal cord injury. Spinal Cord 1999;37:480-4.

35. Heath DL, Vink R. Optimization of magnesium therapy after severe diffuse axonal brain injury in rats. J Pharmacol Exp Ther 1999;288:1311-6.

36. Muir KW, Lees KR. A randomized, double-blind, placebocontrolled pilot trial of intravenous magnesium sulfate in acute stroke. Stroke 1995;26:1183-8.

37. Ustün ME, Gürbilek M, Ak A, Vatansev H, Duman A. Effects of magnesium sulfate on tissue lactate and malondialdehyde levels in experimental head trauma. Intensive Care Med 2001;27:264-8.

38. Crowe MJ, Bresnahan JC, Shuman SL, Masters JN, Beattie MS. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med 1997;3:73-6.

39. Liu XZ, Xu XM, Hu R, Du C, Zhang SX, McDonald JW, et al. Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci 1997;17:5395-406.

40. Lu J, Ashwell KW, Waite P. Advances in secondary spinal cord injury: role of apoptosis. Spine (Phila Pa 1976) 2000;25:1859-66.

41. Nottingham S, Knapp P, Springer J. FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury. Exp Neurol 2002;177:242-51.

42. Ghribi O, Callebert J, Verrecchia C, Plotkine M, Boulu RG. Blockers of NMDA-operated channels decrease glutamate and aspartate extracellular accumulation in striatum during forebrain ischaemia in rats. Fundam Clin Pharmacol 1995;9:141-6.

43. Sameshima H, Ikenoue T. Effect of long-term, postasphyxial administration of magnesium sulfate on immunostaining of microtubule-associated protein-2 and activated caspase-3 in 7-day-old rat brain. J Soc Gynecol Investig 2002;9:203-9.

44. Walter M, van den Bergh and on behalf of the MASH study group. Magnesium sulphate in aneurysmal subarachnoid hemorrhage: A randomized controlled trial. Stroke 2005;36:203-9.

45. Wong GK, Chan MT, Boet R, Poon WS, Gin T. Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study. J Neurosurg Anesthesiol 2006;18:142-8.

46. Brown NM, Martin SM, Maurice N, Kuwana T, Knudson CM. Caspase inhibition blocks cell death and results in cell cycle arrest in cytokine-deprived hematopoietic cells. J Biol Chem 2007;282:2144-55.

47. Kaptanoglu E, Caner H, Solaroglu I, Kilinc K. Mexiletine treatment-induced inhibition of caspase-3 activation and improvement of behavioral recovery after spinal cord injury. J Neurosurg Spine 2005;3:53-6.

48. Oberholzer C, Tschoeke SK, Moldawer LL, Oberholzer A. Local thymic caspase-9 inhibition improves survival during polymicrobial sepsis in mice. J Mol Med (Berl) 2006;84:389-95.

49. Black P, Markowitz RS, Cooper V, Mechanic A, Kushner H, Damjanov I, et al. Models of spinal cord injury: Part 1. Static load technique. Neurosurgery 1986;19:752-62.

319

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):320-326

Original Article

Klinik Çalışma doi: 10.5505/tjtes.2013.05014

Analysis of appropriate tetanus prophylaxis in an Emergency Department Acil serviste yapılan tetanoz proflaksisi uygunluğunun analizi Gözde ŞİMŞEK,1 Erol ARMAĞAN,1 Özlem KÖKSAL,1 Yasemin HEPER,2 Suna ERAYBAR POZAM,1 Vahide Aslıhan DURAK1

BACKGROUND

AMAÇ

In this study, our aim was to identify the validity of the prophylaxis indications for patients who received tetanus prophylaxis, determine the ratio of high-risk wounds to the number of patients with immunity, and to evaluate the tetanus immunity of specific age groups.

Bu çalışmada, tetanoz profilaksisi verilen hastaların profilaksi endikasyonunun doğruluğu, hekim tarafından tetanoz riskli kabul edilen yaraların ve bu hastaların bağışıklık oranının belirlenmesi, belirli yaş gruplarının tetanoz bağışıklığının değerlendirilmesi amaçlandı.

METHODS

GEREÇ VE YÖNTEM

Patients who applied to the Emergency Department (ED) between September 2009 and May 2010 and who were considered for tetanus prophylaxis by his/her primary care physician were included in the study.

RESULTS

A total of 320 patients were evaluated. The average age of the patients was 40.87±15.83 years. A total of 73.1% of the patients were male and 26.8% were female. A total of 40.3% of the patients knew their vaccination history, while 59.7% had no recollection of their vaccination history.

14.7% of the patients had received their last dose within 5 years and 48.1% within 5-10 years; 37.2% of the patients declared that more 10 years had passed since their last vaccination. In 75% of the patients, the tetanus immunoglobulin (Ig)G level was identified as ≥0.1 IU/ml, while 25% of the patients had levels <0.1 IU/ml. The number of patients with protective levels was lower among those who were illiterate or who had only a primary school education, and this difference was statistically significant (p<0.001).

CONCLUSION

Eylül 2009-Mayıs 2010 tarihleri arasında Uludağ Üniversitesi Tıp Fakültesi Acil Servis’ine (AS) başvuran ve birinci basamak hekimi tarafından tetanoz profilaksisi verilmesi uygun görülen hastalar bu çalışmaya alındı.

BULGULAR

Toplam 320 hasta değerlendirildi. Hastaların yaş ortalaması 40,87±15,83 idi. Hastaların %73,1’i erkek, %28,6’sı kadındı. Hastaların %40,3’ü aşılama geçmişini biliyorken, %59,7’si aşılanma geçmişini hatırlamıyordu. Hastaların %14,7’si son dozunu beş yıl içinde alırken, %48,1’i 5-10 yıl içinde almıştı ve %37,2’si 10 yıldan daha fazla bir süre önce son kez aşılanmıştı. Hastaların %75’inde tetanoz immünglobulin (Ig)G düzeyi ≥0,1 IU/ml ve %25’inde tetanoz IgG düzeyi <0,1 IU/ml olarak saptandı.

Okuma yazma bilmeyenlerde ya da sadece ilkokul mezunu olanlarda tetanoz bağışıklığı için koruyucu düzeyler daha düşüktü ve bu fark istatistiksel olarak anlamlı idi (p<0,001).

SONUÇ

The vaccination histories can be misleading. Certain equipment can be used at the bedside to determine a patient’s tetanus immunization status.

Hastalardan alınan aşılanma öyküleri yanıltıcı olabilir ve bu amaçla hastaların yatak başı tetanoz bağışıklık durumunun test edilebileceği cihazlar kullanılabilir.

Key Words: Emergency department; immunization; tetanus.

Anahtar Sözcükler: Acil servis; bağışıklık durumu; tetanoz.

Departments of 1Emergency Medicine, 2Enfectious Diseases, Uludag University Faculty of Medicine, Bursa, Turkey.

Uludağ Üniversitesi Tıp Fakültesi, 1Acil Tıp Anabilim Dalı, 2 Enfeksiyon Hastalıkları Anabilim Dalı, Bursa.

Correspondence (İletişim): Özlem Köksal, M.D. Uludağ Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Görükle Yerleşkesi, 16059 Bursa, Turkey.

Tel: +90 - 224 - 295 32 22 e-mail (e-posta): koksalozlem@gmail.com

320

Analysis of appropriate tetanus prophylaxis in an Emergency Department

Tetanus is a disease characterized by difficulty in swallowing, trismus, opisthotonus posture, and tonic clonic contractions that are usually exacerbated by external stimuli.[1] The cases are usually acute and often fatal.[2] Globally, the groups considered to be at risk for tetanus are uninoculated adult women, the geriatric population, individuals with low education, intravenous drug abusers, people with altered immune systems, and newborns.[3-6] Protection against tetanus is antibody-dependent, and immunization can be conferred by active or passive immunization. Tetanus toxoid is a modified neurotoxin that induces the production of a protective antitoxin.[7] The antitoxin levels decrease with time.

Tetanus vaccination is part of the Expanded Immunization Program (EIP) in Turkey. Tetanus vaccination is a hyperimmune globulin that is indicated for people who are at risk for tetanus and lack a history of vaccination. This is because the immunity that tetanus toxoid confers is a delayed process. Tetanus Immune Globulin (TIG) provides immunity by driving the unbound tetanus toxin away.[1,4,8,9] Human Tetanus Immune Globulin (HTIG) is made from humans and is the first choice for immunization.[10] Another point regarding the prevention of tetanus is the appropriate treatment of patients who present to the Emergency Department (ED).[11-13] In cases of acute injuries, the Centers for Disease Control (CDC) in the United States relies on the properties of the wound and the immunization history of the patient (Table 1) to determine the recommendations for tetanus prophylaxis.

[14] While determining the immunization status, it is important to identify whether the patient has completed a primary vaccination. If a patient’s vaccination history or the history of the previous doses is unknown, it should be assumed that the patient has received no tetanus toxoid dose. These patients require TIG as well as tetanus toxoid during the cleaning and debridement of dirty and large wounds. In cases of clean and small wounds, active immunization with tetanus toxoid is sufficient and passive immunization is not necessary.

[7,15] In patients with a history of insufficient vaccina-

tion, as part of their wound care, the continuation of active immunization should be ensured, and primary vaccination must be completed.[12,14,16] In this study, our aim was to identify the validity of the prophylaxis indications for patients who received tetanus prophylaxis, determine the ratio of high-risk wounds to the number of patients with immunity, evaluate the tetanus immunity of specific age groups, and determine whether prophylaxis is necessary even when vaccinations have been administered in less than a five-year period and when the wounds are clean. Our main goal was to clarify those patient groups to whom tetanus prophylaxis must be administered. We sought to investigate the questions of a) whether prophylaxis should be administered according to the patient’s vaccination history and presence of a high-risk wound for tetanus, and b) whether factors such as the patient’s age and accompanying comorbidities should be considered.

MATERIALS AND METHODS The study was conducted in Uludağ University Medical School Hospital, Department of Emergency Medicine, after approval from the ethics council was received. Patients who applied to the Department of Emergency Medicine of Uludağ University Medical School Hospital between September 2009 and May 2010 and who were considered for tetanus prophylaxis by his/her primary care physician were included in the study. In total, over a nine-month period, 365 patients who were considered candidates for tetanus prophylaxis were included in the study. Patients who were referred from other hospitals or who were administered prophylaxis in another hospital, those who were unwilling to cooperate, and those who did not want to take part in the study were excluded.

Patients who presented to the ED with an injury were evaluated according to the trauma protocol. The patient was informed of the study if the resident had decided to administer tetanus prophylaxis after the initial treatment was given. Patients who agreed to participate in the study were asked to sign informed consent forms. The information relating to the pa-

Table 1. The immunization history of the patient≠

History of tetanus immunization Uncertain or <3 doses ≥3 doses

Clean, minor wound Tdap or Td* Yes No Unless >10 years since last dose No

All other wounds TIG No No

Tdap or Td* Yes No Unless >5 years last dose

TIG Yes No

TIG: Tetanus immune globulin; Tdap: Tetanus, diphtheria, and pertussis; Td: Tetanus-diphtheria; TT: Tetanus toxoid. * Tdap is preferred to Td for adolescents who have never received Tdap. Td is preferred to TT for adolescents who received Tdap previously or when Tdap is not available. ≠ Advisory Committee on Immunization Practices (ACIP) recommendations.

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tients who were included in the study was noted by the emergency resident who evaluated the patient in a form called “Evaluation of the Validity of Administering Tetanus Prophylaxis in the Emergency Ward”. In this form, the patient’s age, gender, birth place, place of residence, level of education, compulsory military service history, vaccination information, history of diabetes or steroid use, location of the injury, depth of the injury, duration of the injury, presence and type of infection, and whether or not the wound was considered high risk for tetanus were recorded.

After consent was given and the patient information was entered into the form, prior to the tetanus vaccination, 4-5 cc of venous blood was drawn. The blood was centrifuged for 5 minutes at 3000 rpm, and the serum obtained was placed in Eppendorf tubes and stored at -83 ºC at the Uludağ University Medical School Blood Center until analysis. Tetanus antibody levels were determined in the Uludağ University Department of Microbiology and Infection ELISA laboratory using the Clostridium tetani 5S IgG ELISA kit (Novatec Immundiagnostica GmBH, Germany), according to manufacturer’s instructions. Individuals with antitoxin levels <0.1 U/ml were considered to have insufficient immunity, whereas levels >0.1 U/ ml were to be considered protective against tetanus.

For these levels, the current guidelines were used as a reference.[6,16-18] For the analysis, the Statistical Package for the Social Sciences (SPSS) 13.0 program for Windows was used. The descriptive statistics and frequency distributions were calculated according to the properties of the variables in the study. For comparison of categorical variables, Pearson chi-square and Fisher’s absolute chi-square tests were used. Statistical significance was set at p<0.05.

RESULTS A total of 365 patients were included in the study; 25 patients were excluded because the serum samples were lost, and 20 patients were excluded because the forms on which the information was gathered were lost.

As a result, 320 patients were evaluated in this study.

The average age of the patients was 40.87±15.83 (1086 years). The majority of the patients who applied to the ED were in their third decade of life. Two hundred thirty-four of the patients (73.1%) were male, and 86 (26.8%) were female. The distribution of the individuals according to age group is shown in Figure 1.

In this study, the evaluated wound characteristics included the depth and type of wound, time interval passed since the injury, presence or not of infection in the wound, type of infection, and whether or not the wound was considered as high risk for tetanus.

In total, 153 (47.8%) patients had injuries in an up322

100

90

90 80 70

65

60 50

47

51

40 30 20

32 19

16

10 0

0-19

20-29

30-39

40-49

50-59

60-69

≥70

Fig. 1. The distribution of the individuals according to age group.

per extremity, whereas 74 (23.1%) had injuries in a lower extremity. Thirteen (4.1%) patients had injuries in multiple locations. The injuries were classified according to the type of the wound as laceration, abrasion, avulsion, piercing by an object, firearm injury, crush wound, bite wound, and burn wound. Of 320 patients, 137 (42.8%) had lacerations, whereas only 2 (0.6%) had firearm injuries. Thirteen (4.1%) patients had more than one type of injury (Table 2). The depths of the injuries were classified as superficial, subcutaneous, facia/tendon, and bone/joint. Superficial injuries were the most common, representing 196 (61.2%) of the injuries, followed by subcutaneous and bone/ joint injuries, representing 74 (23.1%) and 34 (10.6%), respectively.

Table 2. The type and localization of injury

Localization of injury Head/Neck Trunk Perineum Upper extremity Lower extremity >1 localization Type of injury Laceration Abrasion Avulsion Stab wound Firearm injury Crush injury Bite wound Burn wound >1 type

Number (n)

Percent (%)

66 42 5 153 74 13

20.6 13.1 1.5 47.8 23.1 4.06

137 30 20 37 2 24 78 7 13

42.8 9.3 6.25 11.5 0.6 7.5 24.4 2.2 4.06

Temmuz - July 2013

Analysis of appropriate tetanus prophylaxis in an Emergency Department

Table 3. The tetanus vaccination history Vaccination history

Duration

Number (n)

Percent (%)

Known

Unknown Total

<5 years 5-10 years >10 years Total

19 62 48 129 191 320

5.9 19.4 15 40.3 59.7 100

Regarding the duration that had passed since the injury, 259 (80.9%) of the patients declared that they presented to the hospital within the first 6 hours. A total of 129 (40.3%) patients knew their vaccination history, while 191 (59.7%) had no recollection of their vaccination history. Of the 129 patients who knew their vaccination history, 19 (14.7%) had received their last dose within 5 years, 62 (48.1%) had been vaccinated within 5-10 years and 48 (37.2%) declared that more 10 years had passed since the last vaccination (Table 3).

Regarding comorbidities such as immunosuppressive drug use or diabetes mellitus (DM), which might affect the immunity, 40 (12.5%) patients had DM, and 4 (1.3%) were using immunosuppressive drugs. In 240 of the patients (75%), the tetanus immunoglobulin (Ig) G level was identified as ≥0.1 IU/ml, while 80 (25%) patients had tetanus IgG levels <0.1 IU/ml.

When the gender distribution with respect to age was analyzed, with the exception of the 51-60 years of

age group (p=0.01), there was no statistically significant difference between the groups (Table 4). When the education level was considered, the number of patients with protective levels was lower among those who were illiterate or who had only a primary school education, and this difference was identified to be statistically significant (p<0.001). The summary of the relationship between tetanus and immunization status is summarized in Table 5.

DISCUSSION Tetanus is one of the main diseases that can be prevented via vaccination. Although active immunization against tetanus is included in the national vaccination program and vaccination is performed during pregnancy and compulsory military service, tetanus continues to occur. This may be because supplementary dosages are not given regularly, and deficiencies in the application of prophylaxis for tetanus-related injuries are present. The lack of continuation of tetanus immunization is the most important factor affecting the

Table 4. The gender distribution of immunization status with respect to age Age

Immunization status

Tetanus IgG <0.1 IU

Tetanus IgG ≥0.1 IU

Total

Number (n)

Percent (%)

Number (n)

Percent (%)

Number (n)

Percent (%)

15 4

11.5 8.0

116 46

88.5 92.0

131 50

100 100

8 5

23.6 41.7

26 7

76.4 58.3

34 12

100 100

14 8

31.8 72.8

30 3

68.2 27.2

44 11

100 100

11 5

64.8 83.4

6 1

35.2 16.6

17 6

100 100

5 5

62.5 71.5

3 2

37.5 28.5

8 7

100 100

<40* Male Female 41-50# Male Female 51-60α Male Female 61-70¥ Male Female >71ψ Male Female *, #, ¥, ψ: p>0.05; α p=0.01.

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Table 5. Relationship between education level and immunization status Education level

Immunization status Tetanus IgG <0.1 IU

Illiterate Primary school Elementary school High school College Total

Tetanus IgG ≥0.1 IU

Number (n)

Percent (%)

Number (n)

Percent (%)

Number (n)

Percent (%)

8 30 19 14 9 80

47.1 41.7 31.1 14.6 12.2 25

9 42 42 82 65 240

52.9 58.3 68.9 85.4 87.8 75

17 72 61 96 74 320

100 100 100 100 100 100

occurrence of the disease. Because immunization can be provided by supplementary vaccinations, tetanus prophylaxis is one of the most important steps in preventing the disease.[13] For this reason, we evaluated the validity of the tetanus prophylaxis administered in the ED and investigated the immunization status of the patient population.

Various tetanus case evaluations have been reported by different centers throughout Turkey. In three previously conducted studies, it was reported that most of the patients were above the age of 45 years on average and had failed to apply to a health institution after an injury. Furthermore, primary immunization was deficient in 70% of the cases. As a result of these studies, the importance of adult immunization and prophylaxis after a trauma was emphasized.[19-21] Ergönül et al.[22] examined 34 previous cases and demonstrated that adult vaccination and training are important. A study conducted in the Kocaeli region of Turkey demonstrated that the level of protection in the <40 years of age group is 95.1%, whereas in the >40 age group, this level is 65.6%.[23] In a study that evaluated the level of protection in 100 people over the age of 18, 93.1% in the 18-30 age group were protected, and this proportion decreased with age to 20% among people in their 70s.[24] In a study involving 2,094 patients in three provinces, Kurtoğlu et al.[25] found the highest level of protection to be in the 10-19 years of age group. In a study involving 249 people over the age of 40, Öztürk et al.[26] found the level of protection to be 25.3%. While the percentage of protected individuals in the 40-49 age group was 38.2%, the proportion was 19.4% among individuals over 60. In a similar study conducted in the Manisa province, the antitoxin levels of individuals aged 17-72 years were measured. In a total of 143 people, 107 (74.8%) had protective levels, whereas 12 (8.4%) were weakly positive and 24 (16.8%) had negative antitoxin levels.[27] The common findings in all these studies indicate that the decreasing level of tetanus antibody protection with age, lack of supplementary vaccinations in later years, decrease 324

Total

in the immune response, and related tetanus toxoid response can be addressed by vaccination of the older population, vaccination of young people at school, vaccination of males undergoing compulsory military service, vaccination of pregnant women, and by development of vaccination programs for adults. Consistent with these studies, we found that the level of antibody detection decreases with age and that age is an important risk factor for tetanus immunity.

When the level of education of the patients in our study was analyzed, we found that illiterate individuals and primary school graduates were less likely to have protection against tetanus toxin than those with high school and college degrees, and this difference was found to be statistically significant (p<0.001).

Similar to our results, in a study conducted in the United States, it was found that a higher level of education was associated with an increased likelihood of having an immune response to tetanus.[6] In another study conducted in Edirne, it was also found that individuals who were illiterate and primary school graduates were less likely to be protected than middle school and high school graduates. It was also demonstrated that the illiterate population generally consisted of older individuals who had lower antitoxin levels.[28] Other studies that have been conducted in our country have also shown that the level of education is related to an increased likelihood of protection against tetanus.[23,26] This result is correlated with an increased frequency of visits to healthcare providers, a lower number of minor traumas, and a higher rate of hospital admission among women during pregnancy, which has been observed in individuals with a higher education level.

Additionally, considering that 56% of the individuals over 60 who were included in our study were illiterate or primary school graduates, the low level of education of the elder population may explain the low levels of antibodies in this population.

In previous studies investigating the relationship between tetanus antibody levels and underlying comorbidities, conflicting results have been obtained. In Temmuz - July 2013

Analysis of appropriate tetanus prophylaxis in an Emergency Department

our study, we evaluated the individuals who had DM or used a steroid group drug. Among the patients with DM, 12 of 40 (30%) had protective antibody levels ≥0.1 IU/ml, and the levels of antibodies with respect to individuals who did not have DM were found to be significantly different (p<0.001). In our study, there were only four individuals who were using steroid drugs, and two of them (50%) had antibody levels that were under the protective level. The lack of statistical significance of this finding can be attributed to the low number of patients involved in the study.

One of the most important steps in the evaluation of patients entering the ED is the application of tetanus prophylaxis. The Advisory Committee on Immunization Practices (ACIP) has listed the indications for tetanus prophylaxis in routine wound care and has provided recommendations.[14] According to these recommendations, it is important to first distinguish whether a wound is considered high risk for tetanus.

Classical guidelines specify that minor traumas are not at high risk for tetanus. However, some studies have shown that both major and minor injuries may be at risk for tetanus. In our study, 75.3% of the 320 cases were deemed to be at risk for tetanus. Of these, 73.4% of the patients had protective levels of antibodies. A total of 79.7% of the 79 patients who were not considered to be at risk for tetanus had protective levels of antibodies.

As seen from previous studies, tetanus is a disease that can be prevented with a highly protective vaccination. However, due to the problem of adherence to the vaccination programs in developing countries, maternal and neonatal tetanus, and tetanus in the elder population in developed countries, this disease continues to be a cause of mortality. In our study, we have shown that tetanus immunization, especially after the age 40, can only be provided with supplementary vaccinations.

Emergency services are a key factor in the accomplishment of this task. According to our study, patients over 40 must receive tetanus prophylaxis if they have not completed primary immunization, have not received a vaccination dose within 10 years, have diabetes, or have a wound that is at risk for tetanus. It is difficult to distinguish whether a wound is at risk for tetanus. In previously published studies, it has been shown that tetanus develops in 30% of minor injuries.

It has also been demonstrated that most of the tetanus cases are observed in individuals who do not receive care for their wound or who do not present to the hospital after an injury. We believe that the public should be informed about this issue. This study and other studies have shown that the level of protection among individuals who do not recall their vaccination history is approximately 70%. Because of this, the vaccination Cilt - Vol. 19 Sayı - No. 4

histories can be misleading. This further demonstrates the important role of medical records. The dates of previous vaccinations must be recorded. Additionally, certain equipment can be used at the bedside to determine a patient’s tetanus immunization status. The validity of these tests and their cost-effectiveness in an ED setting should be investigated, and their usage should be more widespread. This way, unnecessary vaccinations in younger people can prevented.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Gençer S. Kuduz ve tetanoz profilaksisi. Toplumdan edinilmiş enfeksiyonlara pratik yaklaşımlar. Sempozyum Dizisi 2008;61:223-34. [Article in Turkish] 2. Bleck TP. Clostridium tetani. In: Mandell GL, Douglas RG, Bennett JE, editors. Principles and practice of infectious diseases. 5th edition. New York: Churchill Livingstone; 2000. p.

2537-43.

3. Felek S, editör. Sistemik enfeksiyon hastalıkları. İstanbul: Nobel; 2000.

4. CDC. Tetanus. In: Atkinson W, Hamborsky J, McIntyre L, Wolfe S, editors. Epidemiology and prevention of vaccinepreventable diseases. 10th ed. Washington DC: Public Health Foundation; 2007. p. 71-80.

5. Centers for Disease Control and Prevention (CDC). Tetanus among injecting-drug users-California, 1997. MMWR Morb Mortal Wkly Rep 1998;47:149-51.

6. Gergen PJ, McQuillan GM, Kiely M, Ezzati-Rice TM, Sutter RW, Virella G. A population-based serologic survey of immunity to tetanus in the United States. N Engl J Med 1995;332:761-66.

7. Preventing Tetanus, Diphtheria, and Pertussis Among Adolescents: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines MMWR 55 No. 2006 RR3:1-50.

8. Alagappan K, Rennie W, Narang V, Auerbach C. Immunologic response to tetanus toxoid in geriatric patients. Ann Emerg Med 1997;30:459-62.

9. Rhee P, Nunley MK, Demetriades D, Velmahos G, Doucet JJ. Tetanus and trauma: a review and recommendations. J Trauma 2005;58:1082-8.

10. Hsu SS, Groleau G. Tetanus in the emergency department: a current review. J Emerg Med 2001;20:357-65.

11. Giangrasso J, Smith RK. Misuse of tetanus immunoprophylaxis in wound care. Ann Emerg Med 1985;14:573-9.

12. Capellan O, Hollander JE. Management of lacerations in the emergency department. Emerg Med Clin North Am 2003;21:205-31.

13. Stubbe M, Mortelmans LJ, Desruelles D, Swinnen R, Vranckx M, Brasseur E, et al. Improving tetanus prophylaxis in the emergency department: a prospective, double-blind cost-effectiveness study. Emerg Med J 2007;24:648-53.

14. CDC. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006; 55 (No. RR-17):1-34.

15. Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory committee (ACIP).

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MMWR Recomm Rep 1991;40:1-28.

16. McQuillan GM, Kruszon-Moran D, Deforest A, Chu SY, Wharton M. Serologic immunity to diphtheria and tetanus in the United States. Ann Intern Med 2002;136:660-6.

17. Borrow R, Balmer P, Roper MH. The immunological basis for immunization series. Module 3: tetanus update 2006.

World Health Organization, Geneva, Switzerland; 2007. http://www.who.int/vaccines-documents/DocsPDF07/869. pdf.

18. Crone NE, Reder AT. Severe tetanus in immunized patients with high anti-tetanus titers. Neurology 1992;42:761-4.

19. Saltoglu N, Tasova Y, Midikli D, Burgut R, Dündar IH. Prognostic factors affecting deaths from adult tetanus. Clin Microbiol Infect 2004;10:229-33.

20. Salman C, Sekban N, Döşemeci L, Cengiz M, Yılmaz M, Ramazanoğlu A. Yoğun bakımımızda tetanoz: Onyedi hastada tedavi, komplikasyonlar ve mortalitenin değerlendirilmesi.

Türk Anest Rean Der Dergisi 2007;35:200-8.

21. Çelik M, Solakoğlu C, Taştan E, Erol E, Şenel N.A. Tetanoz olgularımız. Ulusal Travma Dergisi 1995;1:189-91.

22. Ergonul O, Erbay A, Eren S, Dokuzoguz B. Analysis of the

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case fatality rate of tetanus among adults in a tertiary hospital in Turkey. Eur J Clin Microbiol Infect Dis 2003;22:188-90.

23. Dundar V, Yumuk Z, Ozturk-Dundar D, Erdoğan S, Gacar G. Prevalence of tetanus immunity in the Kocaeli Region, Turkey. Jpn J Infect Dis 2005;58:279-82.

24. Ergönül O, Sözen T, Tekeli E. Immunity to tetanus among adults in Turkey. Scand J Infect Dis 2001;33:728-30.

25. Kurtoglu D, Gozalan A, Coplu N, Miyamura K, Morita M, Esen B, et al. Community-based seroepidemiology of tetanus in three selected provinces in Turkey. Jpn J Infect Dis 2004;57:10-6.

26. Oztürk A, Göahmetoğlu S, Erdem F, Mýsgüroğlu Alkan S. Tetanus antitoxin levels among adults over 40 years of age in Central Anatolia, Turkey. Clin Microbiol Infect 2003;9:33-8.

27. Yegane TS, Atman Ü, Kasırga E. İleri yaşlarda tetanus aşısı rapeli gerekli mi? Türk Mikrobiyol Cem Derg 2003;33:14852.

28. Tansel O, Ekuklu G, Eker A, Kunduracilar H, Yuluğkural Z, Yüksel P. Community-based seroepidemiology of diphtheria and tetanus in Edirne, Turkey. Jpn J Infect Dis 2009;62:2758.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):327-332

Original Article

Klinik Çalışma doi: 10.5505/tjtes.2013.23326

Acil serviste “Genişletilmiş Acil Travma Ultrasonografisi” uygulamalarının klinik karar üzerine etkisi Impact of the practice of “Extended Focused Assessment with Sonography for Trauma” (e-FAST) on clinical decision in the emergency department İlhan UZ,1 Aslıhan YÜRÜKTÜMEN,2 Bahar BOYDAK,1 Selen BAYRAKTAROĞLU,1 Enver ÖZÇETE,1 Özgür ÇEVRİM,1 Murat ERSEL,1 Selahattin KIYAN1 AMAÇ

BACKGROUND

Çalışmamızda, “Genişletilmiş Acil Travma Ultrasonografi” (GATUS) uygulamasının, çoklu travma hastasında, karıniçi yaralanma, hemotoraks, yanı sıra pnömotoraks saptamada duyarlılığını, ayrıca invaziv işlem gerekliliğiyle ilişkisini göstermeyi amaçladık.

We aimed to show the sensitivity of Extended Focused Assessment with Sonography for Trauma (e-FAST) for detection of pneumothorax, hemothorax and intraabdominal injury. We also investigated the relationship between e-FAST and need for invasive treatment.

GEREÇ VE YÖNTEM

METHODS

Acil servise başvuran, çoklu travmalı hastalar çalışmaya alındı. Hasta hakkında klinik bilgisi olmayan araştırmacı acil hekimi tarafından yatakbaşı GATUS yapıldı. Supin akciğer grafiği bulguları, yapılan invaziv girişimler kaydedildi. Karın ve toraks bilgisayarlı tomografi (BT) (pnömotoraks düzeyine göre skorlama yapıldı) sonuçlarıysa radyoloji uzman düzeyinde değerlendirildi.

This study included patients who experienced multiple trauma. The emergency physician, who had no clinical information about the patient, performed e-FAST. Findings on a supine chest X-ray and invasive interventions were recorded. The results of abdomen and thorax computed tomography (CT) were reviewed (the size of the pneumothorax was scored).

BULGULAR

RESULTS

BT ile karşılaştırıldığında, karıniçi yaralanma ve hemotoraks için GATUS duyarlılıkları sırasıyla %54,5 ve %71 idi.

GATUS ile tanılanamayan hemotoraks ve karıniçi yaralanmalarda herhangi bir invaziv müdahale yapılamadığı görüldü. Toraks BT’sinde pnömotoraks saptanan 33 (%30,8) hastadan GATUS ile 27 (%25,2) hasta pnömotoraks tanısı aldı (duyarlılık %81,8). Yapılan skorlamaya göre GATUS ile “genişliği 1 cm’den az veya uzunluğu midkoronal çizgiyi geçmeyen” pnömotoraksların atlandığı görüldü. Tüp torakostomi uygulanan hastaların tamamında, GATUS pozitifti.

Compared with CT, the sensitivities of e-FAST for intraabdominal injury and hemothorax were 54.5% and 71%, respectively. The patients with hemothorax and intraabdominal injuries were not identified with e-FAST, didn’t need for invasive intervention. Pneumothorax diagnosis was established in 27 patients with e-FAST (sensitivity 81.8%) from among 33 (30.8%) pneumothorax patients. According to the grading on CT, pneumothoraces less than 1 cm in width and not exceeding the midcoronal line in length were not identified. e-FAST was positive for all patients performed with tube thoracostomy.

SONUÇ

CONCLUSION

GATUS, invaziv işlem gerektirebilecek pnömotoraksların saptanmasında, yüksek duyarlılık ile kullanılabilir. Hemotoraks ve karıniçi yaralanmaların tanınmasındaysa duyarlılığı düşük olmakla beraber invaziv işlem gerekliliğini öngörülmesinde yol gösterebilir.

e-FAST can be used with high sensitivity for determination of pneumothorax requiring invasive procedure. It has low sensitivity in the diagnosis of intraabdominal injury and hemothorax; however, e-FAST can predict the need for invasive procedures.

Anahtar Sözcükler: Acil servis; pnömotoraks; çoklu travma; ultrasonografi.

Key Words: Emergency; pneumothorax; multiple trauma; ultrasonography.

Ege Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir; 2 Akdeniz Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Antalya.

1

Department of Emergency Medicine, Ege University Faculty of Medicine, İzmir; 2Department of Emergency Medicine, Akdeniz University Faculty of Medicine, Antalya, Turkey.

1

İletişim (Correspondence): Dr. Aslıhan Yürüktümen. Akdeniz Üniversitesi Hastanesi, Acil Tıp Anabilim Dalı, 07059 Konyaaltı, Antalya, Turkey.

Tel: +90 - 242 - 249 63 77 e-posta (e-mail): ayuruktumen@akdeniz.edu.tr

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Ulus Travma Acil Cerrahi Derg

Travma nedeni ile acil servislere başvuran olguların değerlendirilmesinde pek çok tanısal yöntem kullanılmaktadır. Hastanın stabilitesine göre, bu tanısal yöntemlerin öncelik sıraları değişmekle birlikte ideal yöntem “yatakbaşı, tekrarlanabilir, noninvaziv ve güvenilir” olarak tanımlanabilir. Çoklu travmalı olgularda, bu ölçütleri sağlayabilen bir tanısal yöntem olan ultrasonografinin (USG) kullanımı, yaklaşık 35 yıllık bir geçmişe sahip olmasına rağmen, 1990’lı yıllarda FAST, “Focused Abdominal Sonography for Trauma” (Travmada Odaklanmış Abdominal Sonografi) kavramıyla eğitim programlarına ve rehberlere girmiştir.

[1,2] “Genişletilmiş Acil Travma Ultrasonografisi” (GATUS) olarak adlandırdığımız “Extended-Focussed Assessment with Sonography for Trauma” (e-FAST) ise son dönemde literatürde yer almaya başlamış, hemotoraks, pnömotoraks ve karıniçi parankimal değerlendirmeyi de uygulamaya dahil eden bir kavramdır.[3,4] Ülkemizde travmalı hastada, acil hekimlerince yapılan GATUS ile karıniçi sıvının tanınmasına ilişkin kısıtlı sayıda çalışma mevcuttur.[5,6] Çoklu travmalı hasta grubunda sıklıkla karşılaşılabilen bir diğer patoloji olan pnömotoraks, tanı ve tedavinin gecikmesi halinde, hayati tehlike yaratabilecek bir durumdur. Başlangıçta, olası spinal yaralanma şüphesi ve immobilizasyon gereksinimi nedeni ile bu grup hastalarda, akciğer değerlendirmesi için öncelikli olarak, sırtüstü pozisyonda anteroposterior (AP) akciğer grafisi çekilmektedir. Ancak, sırtüstü akciğer grafisinin (SAG), pnömotoraks saptamada duyarlılığının düşük olduğu bilinmektedir.[7-10] Bilgisayarlı tomografi (BT), karıniçi yaralanma ve pnömotoraks

saptanmasında, altın standart olmakla birlikte, son yıllarda yapılan çalışmalarla, acil servis hastalarında pnömotoraks değerlendirmesinde, USG’nin duyarlılığının yüksek olduğu bilinmektedir.[7-11] Küçük boyutlu olanları, konservatif olarak tedavi edilebilse de, bir çoklu travma hastasında operasyon esnasında veya sonrasında, uygulanacak pozitif basınçlı ventilasyon, pnömotoraksın, tüp torakostomi (TT) gereksinimi yaratabilecek boyutlara veya tansiyon pnömotoraksa dönüşmesine sebep olabilir. Bu yüzden hangi boyutta olursa olsun pnömotoraks varlığının bilinmesi önemlidir. Yapılan çalışmalarda, GATUS’un travma hastasında, hangi düzeydeki pnömotoraksı saptayabildiği ve bunun invaziv işlem gereksinimi ile ilişkisi ortaya koyulmamıştır. Çalışmamızda, acil hekimi tarafından yapılan GATUS’un, hemotoraks ve karıniçi yaralanmanın yanı sıra pnömotoraks saptanmasındaki duyarlılığını, seçiciliğini ve GATUS’da saptanan pnömotoraks boyutu ile invaziv işlem gereksinimi arasındaki ilişkiyi ortaya koymayı amaçladık.

GEREÇ VE YÖNTEM Çalışma, etik kurul onayı alınmasının ardından, bir üniversite acil servisinde, ileriye dönük olarak gerçekleştirildi. Acil servise, çoklu travma ile gelen 18 yaş üzeri tüm hastalar çalışmaya alındı. Çalışmaya katılım onamı alınamayan veya herhangi bir nedenle (teknik sorunlar, hastanın anstabil olması, endikasyon koyulmaması vb) BT çekilemeyen olgular dışlandı (Şekil 1). Tüm olgulara yatakbaşı, GATUS öncesi veya sonrası, başvurudan sonraki ilk saat içinde, SAG portabl

48627

Çalışma zamanı boyunca acil servise başvuran toplam hasta sayısı

8104

Çalışma zamanı boyunca travma nedeniyle başvuran hasta sayısı

356

Çalışmaya kaydedilen çoklu travmalı hasta sayısı

n=32 Onam alınamayan hasta sayısı n=217 Torakoandominal bilgisayarlı tomografi çekilemeyen hasta sayısı

107

Genişletilmiş Acil Travma Ultrasonografi

Sırtüstü akciğer grafisi

Çalışmaya alınan hasta sayısı

Torakoabdominal bilgisayarlı tomografi

Şekil 1. Çalışmanın akış şeması.

328

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Acil serviste “Genişletilmiş Acil Travma Ultrasonografisi” uygulamalarının klinik karar üzerine etkisi

cihazla (Siemens; Mobilett XP Hybrid) çekildi. Yatakbaşı radyolojik ve USG değerlendirilmeler, iki yıl üzerinde deneyime sahip, hasta hakkında klinik ve ek radyolojik bilgisi olmayan, araştırmacı acil tıp araştırma görevlisi veya acil tıp uzmanı tarafından yapıldı.

Değerlendirme, Sonosite Micromax marka, bir adet 5-10 Mhz compound görüntüleme yapabilen lineer transduser, bir adet 2-5 Mhz arasında compound görüntüleme yapabilen konveks transduser içeren ‘Renkli Doppler Ultrasonografi Cihazı’ ile gerçekleştirildi.

Değerlendirmede, karıniçi yaralanma ve hemotoraks için standart GATUS; dört alan (hepatorenal-pleural, splenorenal-pleural, subksifoid ve rektovesikal (veya douglas) taraması yanı sıra pnömotoraks için her bir hemitoraks dört ayrı alandan (4. veya 5. interkostal aralık ile anterior aksiler hattın kesişimi ile oluşan iki anterior, iki lateral bölgeden) sırtüstü pozisyonda tarandı. Transtorasik “real-time” görüntülemede plevral kaymanın ve kuyruklu yıldız artefaktının (B-Lines) kaybı; “time-motion mod” görüntülemede “stratosfer görüntüsü”nün (Şekil 2) olması durumunda pnömotoraks varlığına karar verildi. İlk stabilizasyon ve USG değerlendirme ardından hastaların toraks ve karın BT (16 kesit, 2 mm kesit kalınlığı, Aquilion-16, Toshiba, Japan) incelemeleri yapıldı. BT değerlendirmeleri, hastanın kliniği ve USG bulgularından habersiz bir radyoloji uzmanı tarafından bağımsız olarak gerçekleştirildi. Altın standart toraks BT’de pnömotoraks yüzdesini matematiksel olarak hesaplamak yerine, oranını derecelendirmek için Wolfman ve arkadaşlarının pnömotoraks sınıflaması referans alınarak oluşturulan derecelendirme Şekil 3 ve Tablo 1’de yer almaktadır.[12] Son olarak yapılan invaziv girişimler ve hastanın akibeti kaydedildi.

Analiz, “SPSS (Statistical Package for the Social Sciences) for Windows 14,0” istatistik programı ile yapıldı. Kategorik değişken analizinde ki-kare ve Fisher kesin testi kullanıldı. Güven aralığı (GA) %95 alındı ve p<0,05 olan istatistiksel farklılıklar anlamlı olarak kabul edildi.

Tablo 1. Toraks bilgisayarlı tomografide

pnömotoraks derecelendirmesi 0 1 2

3 4

Pnömotoraks yok Genişlik 0,5-1 cm, 4 kesitten az Genişlik >1 cm, uzunluğu kalp seviyesinde midkoronal çizgiye uzanan , ≥4 kesit Uzunluğu midkoronal çizgiyi geçecek seviyede Şift veya total pnömotoraks

BULGULAR Çalışmaya alınan 107 hastanın, 86’sı (%80,4) erkek olup, genel yaş ortalaması 36,7±19,8 (1-78) hesaplandı, 77 (%72,0) hasta, trafik kazası, 26 (%24,3) hasta, yüksekten düşme ve dört (%3,7) hasta, diğer nedenlerle acil servise başvurmuştu.

Genişletilmiş Acil Travma Ultrasonografisi’nin, travmada altın standart olarak kabul edilen karın BT’sine göre karıniçi yaralanma saptamada duyarlılığı %54,5 (%95 GA= %33.7 ile %75.3), özgüllüğü %100 bulundu. Olumlu öngörü değeri %100, olumsuz öngörü değeri %89,5 (%95 GA= %83,3 ile %95,6) hesaplandı. GATUS normal saptanan 10 (%9,3) hastada, karın BT’sinde patoloji vardı. Bunlar solid organ patolojileri olup, acil ameliyata gitmeyen hastalardı.

Toraks BT’sinde pnömotoraks saptanan 33 (%30,8) hastadan, GATUS ile 27 (%25,2), SAG ile üç (%2,8) hastaya pnömotoraks tanısı koyulabildi. Çalışmamızda, BT ile kıyaslandığında, GATUS ile pnömotoraks saptama duyarlılığı %81,8 (%95 GA= %68 ile %95,5), özgüllüğü %100, olumlu öngörü değeri %100, olumsuz öngörü değeri %90 bulunmuştur. Toraks BT’deki pnömotoraks derecelendirme sistemimize göre, görülen 3. ve 4. derece pnömotorakslı hastaların tamamında (n=12, %36) GATUS’da pnömotoraks görülmüştür (Tablo 2). BT’deki pnömotoraks derecelendirme sistemimize göre, SAG ile pnömotoraks varlığı değerlendirildiğinde ise, SAG’de saptanan pnömotorakslı has-

Şekil 2. Sağda normal akciğer, solda pnömotoraks hastalarında görülen “stratosfer” bulgusu.

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Ulus Travma Acil Cerrahi Derg

Şekil 3. Toraks bilgisayarlı tomografisinde pnömotoraks derecelendirmesi örnekleri.

taların tamamını (n=3, %9) toraks BT’deki 4. derece pnömotoraks hastalarının oluşturduğu bulunmuştur (Pearson Chi-Square Asymp. Sig. p=0,000).

3. derece pnömotorakslara %66,6 (n=4). 4. derece pnömotoraksların tamamına (n=6) acil TT uygulanmıştır.

Bilgisayarlı tomografide pnömotoraks saptanan hastaların, 16’sında (%14,9) acil TT endikasyonu koyulmuştur. Bu hastaların tamamında GATUS pozitifken, üçünde SAG’de pnömotoraks saptanabilmiştir.

Bu hastalardan 2. derece pnömotorakslara %46 (n=6),

Araştırmanın ikincil sonucu olarak, toraks BT’de hemotoraks saptanan 21 (%19,6) hastadan, 15’inde (%14) GATUS’da hemotoraks görülürken (duyarlılık %71, özgüllük %100), SAG ile yedi (%6,5) (duyarlılık %33,3, özgüllük %97) hastaya bu tanının koyula-

Tablo 2. GATUS ile toraks BT’de pnömotoraks dereceleri arasındaki ilişki Pnömotoraks

Toraks BT

0

1

Toplam

2

3

4

n %

n %

n %

n %

n %

GATUS Var Yok Toplam

1 73 74

3 5 8

12 1 13

6 0 6

6 0 6

1,4 98,6 100

37,5 62,5 100

92,3 7,7 100

100 0 100

100 0 100

n % 28 79 107

26,2 73,8 100

GATUS; Genişletilmiş Acil Travma Ultrasonografisi; BT: Bilgisayarlı tomografi.

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Acil serviste “Genişletilmiş Acil Travma Ultrasonografisi” uygulamalarının klinik karar üzerine etkisi

bildiği görülmüştür. GATUS ile saptanamayan, ancak BT’de hemotoraks gözlenen hastaların hiçbirisine TT uygulanmadığı gözlenmiştir.

TARTIŞMA Travma hastalarının yönetiminde, “FAST”in etkinliğini sorgulayan erken dönem araştırmalardan Miller ve arkadaşlarının[13] çalışmalarında duyarlılık %42, olumlu öngörü değeri %67 olarak saptanmıştır. Parankimal organ hasarı ile serbest sıvı saptama yeterliliğini ayırarak değerlendiren ileriye dönük bir radyoloji çalışmasında ise, 3264 hastanın, 288’inde intraperitoneal kanama saptanmış, USG ile serbest sıvı saptama duyarlılığı %60, özgüllüğü %98; serbest sıvı ve/veya karıniçi organ yaralanmalarını göstermedeki duyarlılığı %67, özgüllüğü %98 olarak bulunmuştur.[14] Karıniçi yaralanması olan stabil hastaların önemli kısmında başvuru anında karıniçi kanama saptanamayabilir.

Ayrıca içi boş organ yaralanmalarında erken dönemde hemoperitoneum oluşmayabilir, USG’nin bunları tanımada yetersizliği bilinmektedir. Blackbourne ve arkadaşlarının[15] tekrarlayan USG ile hemoperitoneumun ve karıniçi parankimal yaralanmanın saptanabileceğini göstermek için yaptıkları çalışmada, ilk USG’nin duyarlılığı %31,1, özgüllüğü %99,8 olduğunu, duyarlılığın tekrarlayan USG ile artırılabileceğini bildirilmişlerdir. Bizim çalışmamızda, BT ile 22 (%20,5) hastada, karıniçi yaralanma tespit edilirken, GATUS ile 12 (%11,2) hastada patoloji saptanmıştır. Altı (%5,6) hasta, acil laparotomiye alınmış ve bunların tamamında GATUS’da serbest sıvı görülmüştür. GATUS, ameliyat edilmesi gereken yaralanmaları yüksek duyarlılık ile saptayabilmiştir. Diğer 10 (%9,3) hasta ameliyat edilmeden izlenen solid organ yaralanmalarıdır.

Tanısal gücünün zayıf olduğu, içi boş organ ve retroperitoneal yaralanmaları bir yana bırakacak olursak USG hemoperitonyum tanımada yüksek duyarlılık ve özgüllükle kullanılabilir. Karıniçi parankimal organ hasarının tespiti için ise daha fazla tecrübe, zaman gerekmekle birlikte çalışmamızda da ortaya çıktığı gibi geçmişe göre daha noninvaziv olan günümüz cerrahi yaklaşım tercihlerinin de ışığında USG’nin, acil cerrahi gerekliliği olan hastaları ayıklamada yardımcı bir yöntem olduğu söylenebilir. Ancak yine de daha büyük çalışmaları içeren araştırmalara ihtiyaç bulunmaktadır.

Pnömotoraks tanısında USG kullanımı ile ilgili ilk çalışma 1987 yılında Wernecke ve arkadaşları tarafından yapılmıştır.[16] Sonrasında Targhetta ve arkadaşları[17] USG kullanarak tanımladıkları iki pnömotorakslı olguyu bildirmişlerdir. Bu olguların tanımlanmasında standart iki boyutlu B mode USG kullanılmış ve eşzamanlı inceleme sırasında akciğer kütlesinin kaybolması yanı sıra plevral kayma hareketlerinin saptanamaması ile pnömotoraks tanısının koyulduğu bildirilmiştir.

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Lichtenstein ve arkadaşları, Ball ve arkadaşları, Kirkpatrick ve arkadaşları “occult” pnömotoraksların tespitinde de USG’nin kullanılabileceğini bildirmişlerdir.

[18-20] Blaivas ve arkadaşları künt travmalı 53 pnömotoraks hastası saptadıkları çalışmalarında akciğer grafiğinin duyarlılığı %75 (%95 GA= %61,7 ile %86,2) ve özgüllüğü %100 (%95 GA= 97,1% ile 100%), acil hekimlerinin yaptığı toraks USG’nin duyarlılığı %98,1 (%95 GA= %89,9 ile %99,9) ve özgüllüğü %99,2 (%95 GA= %95,6 ile %99,9) bildirilmiştir.[9] Bu çalışmada spiral BT yanı sıra, “tüp torakostomi uygulamasında hava çıkışının izlenmesi” referans standart olarak kabul edilmiş ve tüm hastalara BT çekilmemiştir. Yine acil serviste gerçekleştirilmiş, mekanik ventilasyon uygulanan, subkutan amfizemi olan hastaların dışlandığı ve 29 pnömotoraks hastasının saptandığı bir başka araştırmada USG için duyarlılığı %86,2 (%95 GA= %67,4 ile %95,5), özgüllüğü 97,2 (%95 GA= %91,2 ile %99,3) saptanmıştır.[8] Soldati ve arkadaşları[10] 109 hastayı (pnömotorakslı hasta oranı %22) dahil ettikleri araştırmalarında bu oranları sırasıyla %92 ve %99,5 olarak bildirmişlerdir. Biz altın standart olarak 16 kesitli BT kullandığımız araştırmamızda duyarlılığı %81,8, özgüllüğü %100 saptadık. Görüntülemeyi zorlaştırıcı subkutan amfizem ve mekanik ventilasyon uygulaması gibi etmenleri göz ardı etmemiz ve bu tür olgularımızı dışlamamamız olasılıkla duyarlılığı daha düşük bulmamıza neden olmuş olabileceğini düşünüyoruz. Şimdiye kadar yapılan çalışmalarda, altın standart toraks BT’deki pnömotoraks oranı ile GATUS’daki pnömotoraks saptanması arasındaki ilişki ve invaziv girişim gerekliliği ile pnömotoraks saptanma ilişkisi değerlendirilmemiştir. Çalışmamızda, toraks BT’de pnömotoraks skorlaması yapılmış, böylece, GATUS’un hangi düzeydeki pnömotoraksları saptayabildiği değerlendirilmiştir. Ayrıca bu değerlendirme, invaziv işlem gerekliliği ile ilişkilendirilmiştir.

Araştırmamız sonucu GATUS ile “genişliği 1 cm’den az veya uzunluğu midkoronal çizgiyi geçmeyen” pnömotoraksların atlandığı bulunmuştur. Ancak bu gruba tüp torakostomi uygulamasına gerek olmamıştır. Bir başka ifade ile GATUS de pnömotoraks saptanmayan hastalarda invaziv işlem gerekmemiştir.

Ma ve arkadaşları[20] majör travması olan hastaların hemotoraks tespitinde GATUS incelemesinin duyarlılığını, özgüllüğünü ve doğruluk oranını, sırasıyla, %96,2, %100 ve %99,6 olarak tespit etmişlerdir.

Bizim çalışmamızda, hemotoraksı saptamada SAG ile BT karşılaştırıldığında, duyarlılığı %71, özgüllüğü %100 olarak bulunmuştur. USG’de saptanmayan hiçbir hemotoraks için girişim yapılmadığı görülmüştür. GATUS’un tamamen akciğer grafiğinin yerine geçmesi mümkün görünmemekle birlikte, sırtıstü pozisyonunda olan hastalarda, hemotoraks tanısı için 331

Ulus Travma Acil Cerrahi Derg

de tamamlayıcı bilgiler verebileceği ve takipte de tekrarlayan X-ray uygulaması yerine tercih edilebileceği düşünülebilir.

Sonuç olarak, çalışmamızda GATUS’un, pnömotoraks yanı sıra laparotomi ve TT gibi özellikle invaziv girişim gerektirecek karıniçi yaralanma ve hemotoraksı yüksek oranda saptayabilmesi nedeniyle, travmalı hasta değerlendirmesinde öncelikle seçilecek tanısal yöntem olduğu ortaya konmuştur.

Yazar(lar) ya da yazı ile ilgili bildirilen herhangi bir ilgi çakışması yoktur.

KAYNAKLAR 1. Mateer J, Plummer D, Heller M, Olson D, Jehle D, Overton D, et al. Model curriculum for physician training in emergency ultrasonography. Ann Emerg Med 1994;23:95-102.

2. Use of ultrasound imaging by emergency physicians. American College of Emergency Physicians. Ann Emerg Med 1997;30:364-5.

3. Dulchavsky SA, Schwarz KL, Kirkpatrick AW, Billica RD, Williams DR, Diebel LN, et al. Prospective evaluation of thoracic ultrasound in the detection of pneumothorax. J Trauma 2001;50:201-5.

4. Kirkpatrick AW, Nicolaou S, Rowan K, Liu D, Cunningham J, Sargsyan AE, et al. Thoracic sonography for pneumothorax: the clinical evaluation of an operational space medicine spin-off. Acta Astronaut 2005;56:831-8.

5. Coşkun F, Akıncı E, Ceyhan MA, Sahin Kavaklı H. Our new stethoscope in the emergency department: handheld ultrasound. Ulus Travma Acil Cerrahi Derg 2011;17:488-92.

6. Girişgin SA, Koyuncu F, Ergin M, Yıldırım C, Cander B, Fowler J, et al. Interperation of “Basic Ultrasonography Course” in Emergency Medicine. ATUDER 2011;10:46-9.

7. Rowan KR, Kirkpatrick AW, Liu D, Forkheim KE, Mayo JR, Nicolaou S. Traumatic pneumothorax detection with thoracic US: correlation with chest radiography and CT-initial experience. Radiology 2002;225:210-4.

8. Zhang M, Liu ZH, Yang JX, Gan JX, Xu SW, You XD, et al. Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma. Crit Care 2006;10:R112.

9. Blaivas M, Lyon M, Duggal S. A prospective comparison

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of supine chest radiography and bedside ultrasound for the diagnosis of traumatic pneumothorax. Acad Emerg Med 2005;12:844-9.

10. Soldati G, Testa A, Sher S, Pignataro G, La Sala M, Silveri NG. Occult traumatic pneumothorax: diagnostic accuracy of lung ultrasonography in the emergency department. Chest 2008;133:204-11.

11. Wilkerson RG, Stone MB. Sensitivity of bedside ultrasound and supine anteroposterior chest radiographs for the identification of pneumothorax after blunt trauma. Acad Emerg Med 2010;17:11-7.

12. Wolfman NT, Myers WS, Glauser SJ, Meredith JW, Chen MY. Validity of CT classification on management of occult pneumothorax: a prospective study. AJR Am J Roentgenol 1998;171:1317-20.

13. Miller MT, Pasquale MD, Bromberg WJ, Wasser TE, Cox J. Not so FAST. J Trauma 2003;54(1):52-60.

14. Richards JR, Schleper NH, Woo BD, Bohnen PA, McGahan JP. Sonographic assessment of blunt abdominal trauma: a 4-year prospective study. J Clin Ultrasound 2002;30:59-67.

15. Blackbourne LH, Soffer D, McKenney M, Amortegui J, Schulman CI, Crookes B, et al. Secondary ultrasound examination increases the sensitivity of the FAST exam in blunt trauma. J Trauma 2004;57:934-8.

16. Wernecke K, Galanski M, Peters PE, Hansen J. Pneumothorax: evaluation by ultrasound-preliminary results. J Thorac Imaging 1987;2:76-8.

17. Targhetta R, Bourgeois JM, Chavagneux R, Balmes P. Diagnosis of pneumothorax by ultrasound immediately after ultrasonically guided aspiration biopsy. Chest 1992;101:855-6.

18. Lichtenstein DA, Mezière G, Lascols N, Biderman P, Courret JP, Gepner A, et al. Ultrasound diagnosis of occult pneumothorax. Crit Care Med 2005;33:1231-8.

19. Ball CG, Kirkpatrick AW, Laupland KB, Fox DI, Nicolaou S, Anderson IB, et al. Incidence, risk factors, and outcomes for occult pneumothoraces in victims of major trauma. J Trauma 2005;59:917-25.

20. Ma OJ, Mateer JR, Ogata M, Kefer MP, Wittmann D, Aprahamian C. Prospective analysis of a rapid trauma ultrasound examination performed by emergency physicians. J Trauma 1995;38:879-85.

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Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):333-336

Original Article

Klinik Çalışma doi: 10.5505/tjtes.2013.82783

Treatment of acute scrotum in children: 5 years’ experience Çocukluk çağı akut skrotum olgularında tedavi yaklaşımı: 5 yıllık deneyim Volkan Sarper ERİKCİ, Münevver HOŞGÖR, Nail AKSOY, Özkan OKUR, Melih YILDIZ, Ahmet DURSUN, Yusuf DEMİRCAN, Yılmazcan ÖRNEK, İncinur GENİŞOL

BACKGROUND

AMAÇ

A retrospective review was carried out to determine the incidence of various causes and outcome of management in patients with acute scrotum.

Akut skrotum tanısı ile tedavi edilen olgular altta yatan değişik nedenlerin insidansı ve bu olgulardaki tedavi sonuçlarının belirlenmesi amacı ile geriye dönük olarak incelendi.

METHODS

Fifty children had a diagnosis of acute scrotum between 1st January 2007 and 15th May 2012. Age, mode of presentation, associated anomalies, and results of treatment were studied.

Diagnosis of acute scrotum was confirmed by physical examination, Doppler ultrasound and biochemical investigations.

RESULTS

Clinical presentation consisted of sudden swelling and pain in the inguinoscrotal region. The average age was 7.5 years (2 months-14 years). Causes of acute scrotum were orchitis/epididymo-orchitis (O/EO) in 22, strangulated inguinal hernia (SIH) in 16, testicular torsion (TT) in 11, and torsion of testicular appendage (TTA) in 1. Associated urological anomalies were found in 5 patients with O/EO. Medical treatment was applied to patients with O/EO, and surgical treatment was performed in patients with SIH, TT and TTA. CONCLUSION

GEREÇ VE YÖNTEM

1 Ocak 2007 ile 15 Mayıs 2012 tarihleri arasında 50 akut skrotum olgusu tedavi edildi. Yaş, klinik yansıma, ek anomaliler, tıbbi ve cerrahi tedavi sonuçları araştırıldı. Tüm olgularda tanı, fiziksel inceleme, ultrasonografi ve/veya Doppler ultrasonografi ve biyokimyasal incelemelere dayanılarak konuldu.

BULGULAR

Klinik görünüm inguinoskrotal bölgesinde ani şişlik ve ağrı oluşumuydu. Ortalama hasta yaşı 7,5 yıldı (2 ay-14 yaş).

Olguların 22’sinde orşit/epididimo-orşit (O/EO), 16’sında strangüle herni (SH), 11’inde testis torsiyonu (TT), bir olguda da appendiks testis torsiyonu (ATT) saptandı. O/EO olgularının 5’inde eşlik eden ürolojik anomaliler saptandı.

O/EO olguları konservatif olarak, SH, TT ve ATT olguları ise cerrahi olarak tedavi edildi.

In this series, O/EO was found to rank first as the cause of acute scrotum. Immediate surgical treatment in acute scrotum patients, except those with O/EO, is necessary. Associated urological anomalies should be investigated in patients with O/EO.

SONUÇ

Key Words: Epididymo-orchitis; scrotum; strangulated inguinal hernia; testis torsion; torsion of testicular appendage.

Anahtar Sözcükler: Epididimo-orşit; skrotum; strangüle inguinal herni; testis torsiyonu; appendiks testis torsiyonu.

Presented at the 30th National Annual Meeting of the Turkish Association of Pediatric Surgeons (October 17-20, 2012, Ankara, Turkey).

30. Ulusal Türkiye Çocuk Cerrahisi Kongresi'nde sunulmuştur (17-20 Ekim 2012, Ankara).

Department of Pediatric Surgery, Dr. Behcet Uz Children Training and Research Hospital, Izmir, Turkey.

Dr. Behçet Uz Çocuk Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Çocuk Cerrahisi Kliniği, İzmir.

Bu çalışmada E/EO akut skrotum nedeni olarak ilk sırada bulunmuştur. O/EO olanlar hariç akut skrotum hastalarda acil cerrahi tedavi gereklidir. Ayrıca E/EO tanılı olgular ek ürolojik anomaliler açısından değerlendirilmelidir.

Correspondence (İletişim): Volkan Sarper Erikci, M.D. Süvari Cad., Babadan Apt., No: 34, D. 6, 35040 Bornova, İzmir, Turkey.

Tel: +90 - 232 - 411 60 36 e-mail (e-posta): verikci@yahoo.com

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Ulus Travma Acil Cerrahi Derg

Acute scrotal conditions are common in children, and present with scrotal pain, swelling, and redness in the affected hemiscrotum. The true cause is difficult to determine. There are myriad etiologies for this syndrome, including torsion of the testis (TT), torsion of the testicular appendix (TTA), epididymo-orchitis (EO), and strangulated inguinoscrotal hernia (SIH).[1-3] General belief is that EO is rare in children and associated with structural anomalies of the urinary tract.[4-6] The aim of this study was to determine the incidence of various causes in patients with acute scrotal conditions who admitted to our clinic. It was also aimed to assess the outcome of the management.

MATERIALS AND METHODS This is a retrospective study of 50 children diagnosed with acute scrotum between January 2007 and May 2012. Age, mode of presentation, associated anomalies, and results of medical and surgical treatment were studied. Diagnosis of acute scrotum was confirmed by physical examination, ultrasound (US) and/or Doppler US, and biochemical investigations.

All the patients with EO were evaluated with routine urinalysis, urine culture and US for urinary anomalies.

If suspicious findings were determined, such as positive urinalysis and urine culture or upper urinary tract dilatation on US, further investigations including renal scintigraphy and voiding cystourethrography (VCUG) were performed. Medical treatment was applied to patients with urinary tract infection before the VCUG procedure.

RESULTS Clinical presentations of patients consisted of sudden swelling and pain in the inguinal, scrotal or inguinoscrotal region and sometimes symptoms associated with the gastrointestinal system. The age of the patients ranged from the newborn period to 14 years.

With the exception of 9 newborn patients, the average age was 7.5 years (2 months-14 years). The average time intervals between the onset of the symptoms and admission to hospital (SH) and admission to hospital and surgical treatment (AS) in the operated patients were 50.2 hours (8-168 hours) and 3.6 hours (2-4 hours), respectively.

Etiology of acute scrotum is depicted in Table 1.

O/EO was detected in 22 patients; their average age was 7.8 years (1-14 years) and average duration of symptoms was 63.2 hours (24-168 hours). Assessment for possible underlying urogenital anomalies included urinary US in all the patients with EO. Further investigations, including renal scintigraphy and VCUG, were performed in 8 cases who revealed positive urinalysis and urine cultures or US finding of upper urinary tract dilatation. Associated urological anomalies were found in 5 patients: isolated penoscrotal hy334

Table 1. Causes of acute scrotum in our patients Etiology

n

Percent (%)

Orchitis/epididymo-orchitis Strangulated inguinal hernia Testicular torsion Torsion of testicular appendage

22 16 11 1

44 32 22 2

pospadias in 2, utriculus prostaticus associated with penoscrotal hypospadias in 1, bilateral vesicoureteral reflux in 1, and isolated vesical exstrophy in 1. There were 31 episodes of EO in 22 patients. Two patients presented with more than one attack clinically, while only one episode of EO was observed in the other patients. Three of the patients (13.6%) had positive urinalysis (>10 white blood cells per high-power field).

Urine cultures showed infection in 3 children with EO (Pseudomonas), and 19 were uninfected. Diagnosis of EO was confirmed with Doppler US in all patients with EO. They were treated conservatively.

Sixteen of the patients had SIH and most of them had right-sided hernias (13 right; 3 left). The average age of these patients was 1.9 years (22 days-10 years), and 8 of the patients were in the newborn period. The average duration of symptoms was 31.1 hours (8-96 hours). Contents of the hernia sac included mostly jejunoileal intestinal segments (n=13), but other sac contents were Meckel diverticula in 1, appendix vermiformis in 1 and sigmoid colon in 1, and these patients were treated surgically.

Eleven patients presented with TT (9 left; 2 right) and 1 patient with TTA. The average age of patients with TT was 10.9 years (newborn-14 years). Color Doppler US was performed in 10 patients with TT. The average SH and AS durations were 53.1 hours (24-120 hours) and 2.8 hours (2-4 hours), respectively. The average degree of torsion was 540° (360°-1080°). There were 7 clockwise and 2 counter-clockwise torsions.

The rotational direction could not be addressed in 2 patients, and spontaneous detorsion was presumed to have occurred during surgery. The type of torsion was intravaginal in all of the patients. Orchiectomy (O) was performed in 6 patients with parenchymal infarct, and detorsion and orchiopexy (DO) was performed in 5 without parenchymal infarct. For the O and DO groups, the average duration of symptoms was 68.0 and 38.4 hours and average degree of torsion was 510° and 360°, respectively. Routine contralateral testicular fixation with Dartos pouch orchiopexy technique was performed in all the TT patients. The follow-up US was performed 4 weeks after surgery. If any abnormalities regarding sonomorphological findings were detected, US examinations were repeated semiannually. Testicular atrophy was detected in 2 of the DO Temmuz - July 2013

Treatment of acute scrotum in children

patients in the 6th and 18th postoperative months. Excision of a testicular appendage was performed in 1 patient with TTA.

DISCUSSION Every boy with acute onset scrotal pain and swelling requires immediate evaluation. The commonest causes of acute scrotum in children are TT, EO and TTA.[1-3,7] Various incidences have been reported regarding the etiology of pediatric acute scrotum.[1-3] The true incidence of these causes in acute scrotum is unclear, but EO is thought to be uncommon.[8] There were a total of 19993 admissions in the study period, giving an overall acute scrotum incidence of 0.25% in our department. The relatively low percentage of acute scrotum patients in this series[8] with respect to general admissions during the same period may be explained by the local condition of our hospital. Because Doppler US is only available in the daytime, patients presenting symptoms of acute scrotum at night were referred to other medical centers for Doppler US. It is probable that these patients received further treatment where the US investigation was carried out.

The patients’ ages in this study ranged from the newborn period to 14 years. EO occurred most commonly around 8 years (1-14 years). Traditional teaching suggests that EO is rare in children and occurs more frequently among late adolescents.[2,3,5,9,10] Contrary to published reports, only 22.7% of our patients (5 of 22) with EO were found to be around the peripubertal age group. The incidence of positive urinalysis (13.6%) in this study shows similarity with previous reports, in which incidences were between 15%-59%.

[2,5,11] Urine cultures were inconclusive in the majority of the patients in the current study and showed infection with Pseudomonas in 3 patients, and this clinical data is similar to the literature.[12,13] However, the urine culture-proven infection rate of 51.6% has also been reported in children with epididymitis.[14] The incidence of underlying urogenital anomaly in our patients with EO was 22.7% (5 of 22) and is consistent with previous reports.[5,15,16] There is controversy regarding whether all the patients with EO should undergo urinary tract investigation. It has been recommended that all boys with EO should be evaluated for urogenital anomalies.[3] Others suggest further urological assessment only in children with high risk of urinary anomalies.[1,7,16] In the current study, routine use of urinalysis and urine culture with urinary US permitted us to perform selective use of VCUG and renal scintigraphs, which was found to be cost-effective.

Strangulated inguinoscrotal hernia (SIH) is another clinical entity that should be included in the differential diagnosis of acute scrotum in children. There are Cilt - Vol. 19 Sayı - No. 4

reports with varying incidences of SIH in pediatric acute scrotum. In a large series of 1228 children with acute scrotum, the incidence of SIH was reported to be lower than 7%.[15] However, an incidence of up to 49% was also reported.[17] The incidence of SIH (32.7%) in this study is similar to that of Tabari’s series.[18] The average age of patients with SIH in the current study was 1.9 years (22 days-10 years), with half of them in the newborn period, and 81.2% of the patients presented with right-sided hernias. Thus, it is highly recommended that SIH be kept in mind if a newborn presents symptoms compatible with acute scrotum.

With regard to the current study, despite the rather late admission of patients with SIH, no morbidity was observed after surgical treatment.

Testicular torsion (TT) is an urgent condition requiring prompt surgical treatment. In addition to its duration, the degree of rotation has been implicated in the clinical outcome.[19-21] Ischemia can occur as soon as 4 hours after torsion and is almost certain after 24 hours.[22] It was reported that if detorsion occurred in less than 6 hours or after 24 hours, testicular salvage rates of 90% and less than 10% could be achieved, respectively.[23] In Sidler’s series,[1] orchiectomy was performed in 61.2% within 24 to 48 hours of clinical onset. In the current series, orchiectomy was performed in 6 children (54.5%). Two patients with detorsion revealed testicular atrophy in the late follow-up, defined as at least 15% less volume compared to the contralateral testis. If these atrophied testes are not taken into account with regard to testicular salvage, a rather low rate of 27.3% (3 of 11) in this study may be explained by the late diagnosis and treatment. Some patients with a prolonged period of symptoms may have had intermittent torsion or a partial torsion such that the testes may be salvageable. Thus, surgery should never be delayed on the assumption of nonviability based on a clinical estimate of the duration of torsion, as in three of our patients. The testes in these patients could be salvaged by surgical treatment despite the rather long duration of symptoms. The average value of torsion in this series for nonviable testes was slightly higher than in patients who did not undergo orchiectomy (510° versus 360°), in accord with the literature.[24] The duration of symptoms was also found to be longer in orchiectomized children, as may be expected. Although there was a neonate in the TT group, there were no patients with extravaginal torsion, as commonly seen in neonates in this series.

Torsion of the testicular appendix (TTA) is one of the most frequent causes of acute scrotum. Although it is a benign condition and the necrotic tissue is reabsorbed without any sequelae in almost all cases, the clinical presentation is a major challenge to clinicians.

Most of these cases are managed conservatively. The 335

Ulus Travma Acil Cerrahi Derg

case of TTA in the presented series was diagnosed intraoperatively. The incidence of TTA in this series was 2% lower than previous reports.[8,14] This can be explained by the relative low percentage of TTA in our acute scrotum patients or underdiagnosis of this clinical entity.

In conclusion, the most common causes of acute scrotum in this series were O/EO, SIH, TT, and TTA. In light of this study and previous reports, immediate surgical treatment after investigations is necessary in acute scrotum patients, except those with O/EO. With this timely approach, it is anticipated that complication rates will decrease and salvage of affected testes will increase. In addition, associated urological anomalies should be searched in patients with O/EO, and in order to protect the upper urinary system, urinary tract infections should be treated.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Sidler D, Brown RA, Millar AJ, Rode H, Cywes S. A 25year review of the acute scrotum in children. S Afr Med J 1997;87:1696-8.

2. Kadish HA, Bolte RG. A retrospective review of pediatric patients with epididymitis, testicular torsion, and torsion of testicular appendages. Pediatrics 1998;102:73-6.

3. Lewis AG, Bukowski TP, Jarvis PD, Wacksman J, Sheldon CA. Evaluation of acute scrotum in the emergency department. J Pediatr Surg 1995;30:277-82.

4. Merlini E, Rotundi F, Seymandi PL, Canning DA. Acute epididymitis and urinary tract anomalies in children. Scand J Urol Nephrol 1998;32:273-5.

5. Siegel A, Snyder H, Duckett JW. Epididymitis in infants and boys: underlying urogenital anomalies and efficacy of imaging modalities. J Urol 1987;138:1100-3.

6. Likitnukul S, McCracken GH Jr, Nelson JD, Votteler TP. Epididymitis in children and adolescents. A 20-year retrospective study. Am J Dis Child 1987;141:41-4.

7. Burgher SW. Acute scrotal pain. Emerg Med Clin North Am 1998;16:781-809.

8. McAndrew HF, Pemberton R, Kikiros CS, Gollow I. The in-

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cidence and investigation of acute scrotal problems in children. Pediatr Surg Int 2002;18:435-7.

9. Anderson MM, Neinstein LS. Scrotal disorders. In: Neinstein LS, editor. Adolescent health care: a practical guide.

Baltimore: Williams&Wilkins; 1996. p. 464.

10. Pillai SB, Besner GE. Pediatric testicular problems. Pediatr Clin North Am 1998;45:813-30.

11. Gislason T, Noronha RF, Gregory JG. Acute epididymitis in boys: a 5-year retrospective study. J Urol 1980;124:533-4.

12. Graumann LA, Dietz HG, Stehr M. Urinalysis in children with epididymitis. Eur J Pediatr Surg 2010;20:247-9.

13. Haecker FM, Hauri-Hohl A, von Schweinitz D. Acute epididymitis in children: a 4-year retrospective study. Eur J Pediatr Surg 2005;15:180-6.

14. Van Glabeke E, Khairouni A, Larroquet M, Audry G, Gruner M. Acute scrotal pain in children: results of 543 surgical explorations. Pediatr Surg Int 1999;15:353-7.

15. Yang C Jr, Song B, Liu X, Wei GH, Lin T, He DW. Acute scrotum in children: an 18-year retrospective study. Pediatr Emerg Care 2011;27:270-4.

16. Clift VL, Hutson JM. The acute scrotum in childhood. Pediatr Surg Int 1989;4:185-8.

17. Gnassingbe K, Akakpo-Numado GK, Songne-G B, Anoukoum T, Sakiye KA, Kao M, et al. Acute scrotum in children.

[Article in French] Mali Med 2009;24:31-5.

18. Khaleghnejad-Tabari A, Mirshermirani A, Rouzrokh M, Mahmudi M, Baghaiepour MR, Ghaffari P, et al. Early exploration in the management of acute scrotum in children.

Iran J Pediatr 2010;20:466-70.

19. Heindel RM, Pakyz RE, Reinking LN, Cosentino MJ. The effect of various degrees of unilateral spermatic cord torsion on fertility in the rat. J Urol 1990;144:366-9.

20. Sonda LP Jr, Lapides J. Experimental torsion of the spermatic cord. Surg Forum 1961;12:502-4.

21. Tryfonas G, Violaki A, Tsikopoulos G, Avtzoglou P, Zioutis J, Limas C, et al. Late postoperative results in males treated for testicular torsion during childhood. J Pediatr Surg 1994;29:553-6.

22. Ringdahl E, Teague L. Testicular torsion. Am Fam Physician 2006;74:1739-43.

23. Davenport M. ABC of general surgery in children. Acute problems of the scrotum. BMJ 1996;312:435-7.

24. Sessions AE, Rabinowitz R, Hulbert WC, Goldstein MM, Mevorach RA. Testicular torsion: direction, degree, duration and disinformation. J Urol 2003;169:663-5.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):337-342

Original Article

Klinik Çalışma doi: 10.5505/tjtes.2013.89411

Non-operative treatment approach for blunt splenic injury: is grade the unique criterion?

Künt dalak yaralanmalarında ameliyatsız tedavi: Derecelendirme tek kriter midir?

Bülent KOCA,1 Koray TOPGÜL,2 Saim Savaş YÜRÜKER,1 Hamza ÇINAR,1 Bekir KURU1 BACKGROUND

AMAÇ

We aimed to investigate the results of a non-operative approach to blunt spleen injury to re-evaluate the importance of injury grade.

Bu çalışmada, künt dalak yaralanmasına ameliyatsız yaklaşım sonuçlarını irdelemeyi, yaralanma derecesinin önemini yeniden değerlendirmeyi amaçladık.

METHODS

GEREÇ VE YÖNTEM

Thirty-one blunt splenic trauma cases subjected to nonoperative treatment were evaluated retrospectively. The patients were classified into two groups as isolated spleen trauma (ST) group and multi-trauma (MT) group. The hospitalization and blood replacement needs, success of non-operative follow-up, and post-traumatic complications were compared between the two groups. The patients were evaluated via follow-up abdominal ultrasonography (US) and computerized tomography (CT). The results were evaluated with regard to post-splenic trauma complications.

Cerrahi dışı yöntemle tedavi edilen 31 künt dalak yaralanmalı olgu geriye dönük olarak incelendi. Hastalar izole dalak travması (DT) grubu ve çoklu travma (ÇT) grubu olmak üzere iki gruba ayrıldı. İki grup arasında yatış süresi, kan replasmanı ihtiyacı, ameliyatsız izlem başarısı ve travma sonrası komplikasyonlar karşılaştırıldı. Hastalar kontrol karın ultrasonografisi (US) ve bilgisayarlı tomografi (BT) ile değerlendirildi. Elde edilen sonuçlar postsplenik travma komplikasyonları ile ilgili olarak değerlendirildi.

RESULTS

BULGULAR

According to the organ injury scale of the American Association for the Surgery of Trauma, 25.8% were grade-1, 32.2% grade-2, 29% grade-3, and 12.9% grade-4 injuries.

It was observed that the transfusion amount was directly proportional to the injury grade. All patients with grade-4 injury and 14 patients with MT were treated successfully with the non-operative method. Splenic pseudoaneurysm developed in one patient in the MT group. One patient was diagnosed with late splenic rupture.

CONCLUSION

Hemodynamic stability is the most important criterion for the indication of non-operative treatment. However, in wellselected cases, patients with grade 4 splenic traumas and those with extra-splenic injuries could also be treated successfully with the non-operative method.

Amerikan Travma Cerrahisi Derneği organ hasarı skoruna göre, olguların %25,8’inde derece 1, %32,2’sinde derece 2, %29’unda derece 3 ve %12,9’unda derece 4 yaralanma vardı. Transfüzyon miktarının yaralanma derecesi ile doğrudan orantılı olduğu görüldü. Ortalama yatış süresi MT grubunda daha uzundu. Derece 4 yaralanma ve çoklu travmalı olan 14 hasta ile tüm hastalar ameliyatsız yöntem ile başarıyla tedavi edildi. MT grubunda bir hastada splenik psödoanevrizma gelişti. Bir hastada geç dalak rüptürü tanısı kondu.

SONUÇ

Hemodinamik stabilite konservatif tedavi endikasyonu için en önemli ölçüttür. Ancak, iyi seçilmiş olgularda 4. derece dalak yaralanması olan ve dalak dışı yaralanmalar da ameliyatsız tedavi ile başarılı bir şekilde tedavi edilebilir.

Key Words: Blunt splenic trauma; complication; injury grade; nonoperative management.

Anahtar Sözcükler: Künt dalak travması; komplikasyon; yaralanma derecelendirmesi; ameliyatsız tedavi.

Department of General Surgery, Ondokuz Mayıs University Faculty of Medicine, Samsun; 2 Department of General Surgery, Medical Park Samsun Hospital, Samsun, Turkey.

Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Samsun; 2 Medical Park Samsun Hastanesi, Genel Cerrahi Bölümü, Samsun.

1

1

Correspondence (İletişim): Koray Topgül, M.D. Medical Park Samsun Hastanesi, Genel Cerrahi Bölümü, Atakum, Samsun, Turkey.

Tel: +90 - 362 - 311 40 40 e-mail (e-posta): ktopgul@gmail.com

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Ulus Travma Acil Cerrahi Derg

In recent years, a non-operative approach for blunt spleen injuries has become the first choice in hemodynamically stable patients with grades 1, 2 and 3 injuries. Preservation of the spleen decreases the risk of early surgical complications such as adjacent organ injury, wound infection, pancreatitis, pleural effusion, and atelectasia as well as late splenectomy complications such as sepsis, serious infections and thromboembolic events.[1,2] Generally, splenectomy is an easy operation for trauma surgeons, while preservation of the spleen is a more laborious procedure. On the other hand, preserving the spleen is important in terms of early- and late-period outcomes.

For many years, we have used a non-operative treatment and follow-up approach in blunt splenic trauma patients in our clinic. In the present study, we investigated the complications of splenic trauma, the incidence of which increases as non-operative treatment becomes more widespread, and present the results of the non-operative approach to blunt spleen injury in our patients. In addition, we aimed to compare with the treatment results of multi-organ trauma patients and isolated splenic injury patients who were treated by the non-operative method. Concurrently, we revisited the algorithms related to this issue.

MATERIALS AND METHODS This study was conducted in Department of General Surgery Ondokuz Mayıs University Faculty of Medicine between January 2008 and December 2010.

Thirty-one blunt splenic trauma cases subjected to non-operative treatment among the 45 blunt splenic trauma cases were evaluated retrospectively. Spleen injuries were classified according to the Abbreviated Injury Scale (AIS). The patients were classified into two groups as “isolated spleen trauma” (ST group) or ‘’multi-trauma” (MT group). The hospitalization and blood replacement needs, success of non-operative follow-up, and post-traumatic complications were compared between the two groups. After their discharge, the patients were evaluated via follow-up abdominal ultrasonography (US) and computerized tomography (CT). Interviews with the patients were conducted, and information about their current health status was obtained. The results were evaluated with regard to post-splenic trauma complications.

Statistical analysis The statistical analysis was performed (with variance analysis and chi-square tests) by using the software Office 2007 Statistical Package for the Social Sciences (SPSS) 13. A p value <0.05 was considered statistically significant.

RESULTS The median age of the 31 patients included in this 338

study, who had splenic injury due to blunt abdominal trauma and were subjected to treatment with non-operative methods, was 46 (range, 18-79) years. Eighteen patients (58%) were male and 13 (42%) were female.

Isolated splenic injury was observed in 17 patients (55%) and intra-abdominal multiple organ injury in 14 patients (45%). Hepatic injury was observed in 7 patients (22.5%), surrenal injury in 4 patients (12.9%), renal injury in 2 patients (6.4%), and hematoma in the small intestinal mesothelium in 1 patient (3.2%). Thirteen patients (41.9%) had rib fracture at the left thorax and 5 patients (16.1%) had hemothorax. Nine (29%) of the patients were injured by in-vehicle traffic accident, 16 (51.6%) by falling from height, 4 (12.9%) by stroke, and 2 (6.4%) by out-of-vehicle accident. According to the organ injury scale of the American Association for the Surgery of Trauma, 8 patients (25.8%) had grade-1, 10 patients (32.2%) grade-2, 9 patients (29%) grade-3, and 4 patients (12.9%) grade-4 injuries (ST group: 5 patients grade-1, 6 patients grade-2, 4 patients grade-3, 2 patients grade-4, and MT group: 3 patients grade-1, 4 patients grade-2, 5 patients grade-3, 2 patients grade-4). Thirty-five units of erythrocyte suspension were given to the 31 patients. We observed that 8 units of blood transfusion were given to the 17 patients with isolated spleen injury (ST) and 27 units of blood transfusion to the 14 MT patients. 1.1 units of erythrocyte suspension per patient were given. 0.27 units of erythrocyte suspension per patient were given to patients with grade 1-2 injury versus 2.3 units per patient given to patients with grade 3-4 injury. It was observed that the transfusion amount was directly proportional to the injury grade. No blood transfusion was given to the group of 17 patients with grade 1-2 ST, while 1.33 blood transfusions per patient were given on average to the group consisting of those with grade 3-4 injury. The average blood transfusion per patient was 1.92 units in the MT group, with 0.71 units in the group with grade 1-2 and 2.66 units in the group with grade 3-4 injuries (Table 1).

The amount of the blood transfusion was significantly higher in the grade 1-2 group with MT as compared with the ST group (p=0.048). In the grade 3-4 group, the amount of blood transfusion was higher in the MT group; however, the difference showed borderline significance (p=0.051). It was observed that most of the patients in the MT group subjected to transfusion were those with hepatic injury and hemothorax.

During the follow-up period, the hemodynamics of one patient (in the grade-3 ST group) was impaired on the 5th day; his hematocrit was 21 in spite of administration of 3 units of erythrocyte suspension. On the follow-up CT, the subcapsular splenic hematoma identified during the first CT was seen to have ruptured and led to disseminated hemoperitoneum, although it was not present on the first CT. Diagnosis of late Temmuz - July 2013

Non-operative treatment approach for blunt splenic injury

Table 1. The duration of hospitalization and replacement quantities of the two groups

Length of stay Grade 1-2 Grade 3-4 Replacement Grade 1-2 Grade 3-4

Isolated group

Multi-trauma group

p

3.18 7

3.85 9.57

0.084 0.234

0 1.33

0.71 2.66

0.048 0.051

Chi-square test.

splenic rupture was established and splenectomy was The patient was discharged after nine days of hospitalization. Thirty patients (97%) were discharged after having been treated successfully with a non-operative approach. The average hospitalization period was 5.51 days (3.44 days in grade 1-2 and 8.38 days in grade 3-4). The average hospitalization period was 4.52 days in the ST group (3.18 days in grade 1-2 and 7 days in grade 3-4) and 6.7 days in the MT group (Table 1). The hospitalization period was longer in the MT group; however, no significant differences were found (p=0.084 for grade 1-2 and p=0.234 for grade 3-4). All of the 4 patients with grade-4 injury (Fig. 1a) and 14 patients with MT were treated successfully with the non-operative method. In 1 patient in the MT group (grade-3 injury), splenic pseudoaneurysm appeared on the 7lh day follow-up abdominal CT (Fig. 1b), and the patient underwent angiographic embolectomy in the department of radiology (Fig. 2). The patient was discharged after 10 days of hospitalization. He is in good health after his discharge (for 14 months). Ten of the 31 patients included in the study were over 55 years old (32.2%). Four of the 10 patients over 55 years old were in the MT group. One patient was 76 years old and had grade-4 MT. All of the patients in this group

(a)

were treated with a non-operative method. None of the patients had post-traumatic complications. No significant statistical differences in the hospitalization period (p=0.21) or amount of blood transfusions (p=0.18) were found in the MT group.

The median follow-up period of patients included in the study was 28 months. In the evaluations for the post-traumatic splenic complications, one patient was diagnosed with late splenic rupture, and one patient with pseudoaneurysm; however, pseudocyst was not observed. The incidence of complication was 6.45% in the patients with splenic trauma during the non-operative treatment.

One of two patients with post-splenic trauma complication was from the ST group and the other was from the MT group. No differences were found between the two groups in terms of the post-traumatic complications.

DISCUSSION After the liver, the spleen is the second most commonly injured intra-abdominal organ in blunt abdominal trauma, with an incidence of 32%.[3] The most common causes for the blunt spleen injury, as in our

(b)

Fig. 1. (a) Grade-4 spleen injury. (b) Image of pseudoaneurysm in CT. Cilt - Vol. 19 Say覺 - No. 4

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limitations except regarding hemodynamic status and comorbid factors. Hemodynamic stability is the most important criterion for non-operative treatment indication.[11] The radiological grade of the injury is an important criterion; however, in well-selected cases, grade-4 spleen traumas and extra-splenic injuries may be treated successfully with a non-operative approach as well as in grade 1-2-3 injuries.

Fig. 2. Angiographic image of the pseudoaneurysm before and after embolization.

study, are “in-vehicle” accidents, “out of vehicle” accidents, falls from height, and stroke. In patients with splenic injury, splenectomy had been the only treatment method for years. In the 1970s, when spleen functions and the post-splenectomy complications were understood more clearly, the spleen-preserving surgical methods became the preferred approach. The most recent development in traumatic splenic injuries is the non-operative treatment. It has been reported that 60% of blunt spleen injuries may be treated successfully with non-operative treatment.[4] In our series, the incidence of non-operative treatment was 66.6%.

It is known that the spleen has several important functions, including immunology, coagulation, storage, filtration,[5] iron metabolism, and wound healing.

The spleen takes part in alternative complement system activation, tuftsin production, T and B lymphocyte maturation, and iron and factor 8 storage.[6] Mortality is 50-70% in post-splenectomy sepsis, even when optimal antibiotic therapy and supportive care are provided.[7] In the early post-splenectomy period, complications including hemorrhage, adjacent organ injury, wound infection, pancreatitis, and pleural effusion may occur. Patients treated with a non-operative method are protected against all of these complications.

Therefore, at present, the non-operative method is the first choice in suitable patients.[8] At this point, patient selection becomes important in decision-making for the non-operative method of treatment. Patients with grade 3-4 injury, above 55 years of age, who received 4 units of blood transfusion during the first 24 hours, with head traumas, and with intraabdominal MTs were excluded from the non-operative treatment group in many studies.[9,10] In our study, patients with grade-4 injury, MT and above 55 years of age were treated successfully with non-operative treatment.

Regarding patient selection for non-operative treatment, we consider that it is not logical to impose strict 340

Ultrasonography (US), CT and diagnostic peritoneal lavage (DPL) may be used as a diagnostic method for splenic injury. US can identify hemoperitoneum with 90-93% sensitivity; however, its sensitivity for determining the splenic trauma classification is lower.

[12] Furthermore, it is not adequate for detecting small intestine, colon, mesothelium, and retroperitoneal injuries.[13] The risk of false- positives in patients with hematuria and pelvic and vertebral fracture is high.

[14] Since it is a fast and easy-to-use method for patients with impaired hemodynamics, it may be the first choice for diagnosis. In most trauma centers, US is used to monitor low-grade splenic injuries.[15] CT is the gold standard for the diagnosis of spleen injury following a blunt abdominal trauma, especially in patients with stable hemodynamics.[8] CT gives clear information about other peritoneal and retroperitoneal organs as well as the amount of intraabdominal hemorrhage, and in addition, may reveal pseudoaneurysms and arteriovenous fistulas in the spleen.[16] In our clinic, we prefer to use CT as the first choice for evaluating blunt abdominal traumas in hemodynamically stable patients. DPL is a diagnostic technique that can be used for diagnosis of blunt abdominal traumas, and it can identify hemoperitoneum with 97% sensitivity.[17] However, it cannot give information about the source of the hemorrhage. If the spleen trauma is identified by US or CT, we do not perform DPL in our clinic.

In our clinic, we prefer to use CT as the first choice in the diagnosis stage in hemodynamically stable patients, and we classify the cases according to the AIS. The grade 1-2-3-4 patients with stable hemodynamics and without head trauma are treated with non-operative methods, irrespective of their ages. In patients with grade 1-2 and isolated spleen injuries, we prefer US as the first choice during the follow-up process, since it is cheap and easy to perform. In patients with grade 3-4 isolated spleen injuries and in all grades of MT patients, CT is used during the follow-up.

The last entity we encountered in consequence of the application of non-operative treatment is postsplenic trauma complications. Late splenic rupture, splenic pseudocyst, arteriovenous fistula, and splenic pseudoaneurysms are the complications observed late after spleen traumas. Late splenic rupture has an incidence of 1% and mortality rate of 5-15% and occurs Temmuz - July 2013

Non-operative treatment approach for blunt splenic injury

4-8 days after the trauma.[18] The mechanism causing the rupture is subcapsular hematoma, pseudocyst or rupture of the pseudoaneurysm.[19] Arteriovenous fistula arises after blunt abdominal trauma, as a result of which the vein in the trauma area opens to the existing splenic artery aneurysm or to the post-traumatic pseudoaneurysm.[20] Splenectomy may be used for its treatment. Angiography is a strong alternative to surgery, since it has a low-risk potential and lower complication risk in comparison with splenectomy.[21] Pain, fever, and hemorrhage may be observed after angioembolization.

At the conclusion of the present study, we revisited and presented the algorithm of the conservative treatment of splenic injuries according to our clinical experiences, as shown in Figure 3.

In conclusion, hemodynamic stability is the most important criterion for the indication of non-operative treatment in blunt splenic trauma.[14,21] The radiological grade of the injury is an important criterion. However, in well-selected cases, patients over 55 years, with grade-4 splenic traumas and with extra-splenic injuries could also be treated successfully with the

Blunt abdominal trauma, spleen laceration Is patient hemodynamically stable?

CT

Grade 1-2-3-4 Hemothorax Liver and kidney injury

Monitoring Blood pressure, pulse, respiration, fever, urine (Foleyâ&#x20AC;&#x2122;s soundingline), central venous catheterization

After 48 hours USG

YES

NO

Grade 5 Colon, intestine, stomach injury Head trauma

First 48 hours Hourly vital signs recording, blood count every 6 hours and abdomen examination, oral nutrition stopped, absolute immobilization

Regression findings, stable

Grade 1-2 isolated

SURGERY

Progression findings, unstable hemodynamically

Oral nutrition regivven, In-bed mobilization, vital signs recording every 4 hours

Grade 3-4 and/or multiple trauma

Discharge after 3-4 days

15 days resting in bed, USG+blood count after 15 days, back to daily activities if USG and blood count are normal, full activity after 4 weeks

USG

Progression, complication, instability

SURGERY

Follow-up CT after 7 days Regression?

Discharge, 15 days resting in bed, USG+blood count after 15 days, back to daily activities after 15 days, CT after 4 months and full activity

Fig. 3. The algorithm that is applied in our clinic for blunt spleen trauma.

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non-operative approach, in addition to those with grade 1-2-3 injuries.

We believe that the spleen is an invaluable organ, and as such, surgeons should strive to protect it by reason of its many vital functions.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Mohren M, Markmann I, Dworschak U, Franke A, Maas C, Mewes S, et al. Thromboembolic complications after splenectomy for hematologic diseases. Am J Hematol 2004;76:143-7.

2. Durakbasa CU, Timur C, Sehiralti V, Mutus M, Tosyali N, Yoruk A. Pediatric splenectomy for hematological diseases: outcome analysis. Pediatr Surg Int 2006;22:635-9.

3. Smith J, Caldwell E, D’Amours S, Jalaludin B, Sugrue M. Abdominal trauma: a disease in evolution. ANZ J Surg 2005;75:790-4.

4. Cales RH, Trunkey DD. Preventable trauma deaths. A review of trauma care systems development. JAMA 1985;254:1059-63.

5. Hansen K, Singer DB. Asplenic-hyposplenic overwhelming sepsis: postsplenectomy sepsis revisited. Pediatr Dev Pathol 2001;4:105-21.

6. Altamura M, Caradonna L, Amati L, Pellegrino NM, Urgesi G, Miniello S. Splenectomy and sepsis: the role of the spleen in the immune-mediated bacterial clearance. Immunopharmacol Immunotoxicol 2001;23:153-61.

7. Holdsworth RJ, Irving AD, Cuschieri A. Postsplenectomy sepsis and its mortality rate: actual versus perceived risks. Br J Surg 1991;78:1031-8.

8. Cadeddu M, Garnett A, Al-Anezi K, Farrokhyar F. Management of spleen injuries in the adult trauma population: a tenyear experience. Can J Surg 2006;49:386-90.

9. Knudson MM, Maull KI. Nonoperative management of solid organ injuries. Past, present, and future. Surg Clin North Am 1999;79:1357-71.

10. Patcher HL, Liang HG, Hofstetter SR. Liver and biliary tract

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trauma. In: Mattox KL, Felliciano DV, Moore EE, editors.

Trauma. 4th ed. New York: Mc Graw Hill; 2000. p. 633-82.

11. Heuer M, Taeger G, Kaiser GM, Nast-Kolb D, Kühne CA, Ruchholtz S, et al. No further incidence of sepsis after splenectomy for severe trauma: a multi-institutional experience of The trauma registry of the DGU with 1,630 patients. Eur J Med Res 2010;15:258-65.

12. van der Vlies CH, van Delden OM, Punt BJ, Ponsen KJ, Reekers JA, Goslings JC. Literature review of the role of ultrasound, computed tomography, and transcatheter arterial embolization for the treatment of traumatic splenic injuries.

Cardiovasc Intervent Radiol 2010;33:1079-87.

13. Schnüriger B, Kilz J, Inderbitzin D, Schafer M, Kickuth R, Luginbühl M, et al. The accuracy of FAST in relation to grade of solid organ injuries: a retrospective analysis of 226 trauma patients with liver or splenic lesion. BMC Med Imaging 2009;9:3.

14. Miller MT, Pasquale MD, Bromberg WJ, Wasser TE, Cox J. Not so FAST. J Trauma 2003;54:52-60.

15. Boulanger BR, McLellan BA, Brenneman FD, Wherrett L, Rizoli SB, Culhane J, et al. Emergent abdominal sonography as a screening test in a new diagnostic algorithm for blunt trauma. J Trauma 1996;40:867-74.

16. Miller LA, Shanmuganathan K. Multidetector CT evaluation of abdominal trauma. Radiol Clin North Am 2005;43:107995.

17. Forsythe RM, Harbrecht BG, Peitzman AB. Blunt splenic trauma. Scand J Surg 2006;95:146-51.

18. Kluger Y, Paul DB, Raves JJ, Fonda M, Young JC, Townsend RN, et al. Delayed rupture of the spleen-myths, facts, and their importance: case reports and literature review. J Trauma 1994;36:568-71.

19. Freiwald S. Late-presenting complications after splenic trauma. Perm J 2010;14:41-4.

20. Maloo MK, Burrows PE, Shamberger RC. Traumatic splenic arteriovenous fistula: splenic conservation by embolization.

J Trauma 1999;47:173-5.

21. Salis A, Pais SO, Vennos A, Scalea T. Superselective embolization of a traumatic intrasplenic arteriovenous fistula. J Trauma 1999;46:186-8.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):343-347

Original Article

Klinik Çalışma doi: 10.5505/tjtes.2013.32457

Thoracic aortic aneurysms after blunt trauma Künt travmalardan sonra oluşan torasik aort anevrizmaları İrfan TAŞOĞLU, Doğan Emre SERT, Gökhan LAFÇI, Bahadır GENÇ, Kemal KAVASOĞLU, Ahmet Tulga ULUS, Mustafa PAÇ

BACKGROUND

AMAÇ

Aortic injury after blunt trauma that is missed during the first admission will soon be seen as a chronic aneurysm.

The objective of this study is to show the importance of the diagnosis and appropriate treatment of these aneurysms.

Künt travmalardan sonra oluşan aort hasarı erken dönemde tanı almayıp yıllar içinde yaşamı tehlikeye atan kronik anevrizmalar şeklinde görülebilir. Bu çalışmanın amacı, bu anevrizmaların tanı ve uygun tedavisinin önemini göstermektir.

METHODS

Between 2009 and 2012, 8 patients (mean age, 50±31 years) diagnosed with chronic traumatic aortic aneurysm were treated with either thoracic endovascular aortic repair (TEVAR) or conventional surgery 20 years on average after the trauma.

RESULTS

GEREÇ VE YÖNTEM

2009-2012 arasında kronik travmatik aort anevrizması tanısı alan sekiz hasta (ortalama 50±31 yaş), travmadan ortalama 20 yıl sonra torasik endovasküler aort tamiri (TEVAR) ya da açık cerrahi ile tedavi edildi.

BULGULAR

Treatments included TEVAR in four patients, conventional surgery in two patients, and hybrid intervention in one patient. One patient died postoperatively. One patient had an endoleak requiring a repeat TEVAR, which was successful. Brachial embolectomy was performed after placing the endovascular stent. No paraplegia or lower extremity ischemia was seen. One patient died preoperatively due to rupture of the aneurysm.

Sekiz hastanın dört tanesi TEVAR, iki tanesi açık cerrahi, bir tanesi ise hibrid girişimle tedavi edildi. Bir hasta ameliyat sonrası dönemde hayatını kaybederken, bir tanesine tip 1 endoleak nedeniyle tekrar başarılı TEVAR işlemi uygulandı; bir hastaya ise endovasküler greft sonrası tespit edilen brakiyal emboli nedeniyle embolektomi yapıldı.

Parapleji, alt ekstremite iskemisi ve başka bir komplikasyon görüldi. Bir hasta ameliyat öncesi dönemde anevrizma rüptürüne bağlı olarak hayatını kaybetti.

CONCLUSION

SONUÇ

Chronic traumatic aortic aneurysms may cause general symptoms years after a blunt trauma. Aortic injury must always be considered in the assessment and follow-up of trauma patients.

Künt travmalara bağlı aort anevrizmaları, travmadan yıllar sonra genel olarak görülen semptomlara yol açabilir. Travma hastasının izlem ve takibinde aortik anevrizma mutlaka akılda tutulmalıdır.

Key Words: Blunt; chronic aortic aneurysms; TEVAR; trauma.

Anahtar Sözcükler: Künt; kronik aortik anevrizma; TEVAR; travma.

Blunt non-penetrating aortic injuries are very mortal lesions, with a high mortality rate, with 80-90% dying in the first hour after the accident, and these injuries have been implicated as the second most common cause

of death in the trauma patient.[1,2] In approximately 2% of these patients, though the injury is missed during the first admission, patients live long enough to develop a chronic aortic aneurysm, which signifies rupture.[3]

Department of Cardiovascular Surgery, Turkey Yuksek Ihtisas Hospital, Ankara, Turkey.

Türkiye Yüksek İhtisas Hastanesi, Kalp ve Damar Cerrahisi Kliniği, Ankara.

Correspondence (İletişim): İrfan Taşoğlu, M.D. Türkiye Yüksek İhtisas Hastanesi, Kalp ve Damar Cerrahisi Kliniği, Sıhiye, Ankara, Turkey.

Tel: +90 - 312 - 306 18 16 e-mail (e-posta): irfantasoglu@yahoo.com

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Ulus Travma Acil Cerrahi Derg

These patients can present with general symptoms like cough, hoarseness and pain in the epigastrium or back years after the accident. The most common symptom was hoarseness in our patients.

The objective of this study was to emphasize the importance of early imaging in trauma patients and to keep aortic blunt injury in mind when obtaining a medical history of the patient with such symptoms.

MATERIALS AND METHODS From August 2009 to April 2012, we selected eight patients with a history of blunt trauma - 7 males and 1 female - from 128 descending aortic aneurysm patients admitted to and treated in our department (Table 1). The study population’s mean age was 50±31 years (median, 54 years; range, 30-61). All patients had a history of blunt trauma. Five (62.5%) of them had a previous motor vehicle accident, 2 (25%) had an accidental fall and 1 (12.5%) was exposed to a long vehicle sudden tire blowout. Demographic characteristics, operation data, postoperative course, and intensive care unit and ward complications were collected from hospital medical records. In all the cases, thoracoabdominal computed tomography angiography (CTA) with an interval slice of 1 millimeter was performed to evaluate the entire aorta and possible accompanying injuries of the other organ systems. Three-dimensional (3D) reconstruction of the images was performed. A cardiovascular interventional team involving cardiothoracic surgeons and interventional radiologists then discussed and decided on the procedure. After discharge, patients were called in for follow-up at the first week, first month and sixth month.

RESULTS Patients’ ages ranged from 30 to 61 years, and the median age was 54. The interval between the time of injury and surgical intervention (8 patients) ranged from 18 days to 44 years (mean, 20 years). Types of aortic lesions were descending thoracic aortic aneurysm in 7 patients and combined arch and descending aortic aneurysm in 1 patient. Six patients (75%) had a saccular type and two (25%) had fusiform aneurysms. We presumed the etiology of the aneurysms as trauma for the following reasons: The patients were not elderly and had no systemic inflammatory disease, and their physical examination criteria were not concordant with Marfan syndrome. Furthermore, they had no hypertension, no documented atherosclerotic vascular disease, no documented prior chronic infectious state (syphilis, brucella), and no family history of aneurysms, and lab values of infectious markers were normal. All had a serious trauma history. Hoarseness was the most common symptom.

None of them was in critical condition. According to the medical records, none of them, at first admission after trauma, was assessed with thoracic CT, and thus were not diagnosed.

Four patients underwent thoracic endovascular aortic repair (TEVAR), two patients underwent a conventional surgical operation in which a Dacron graft interposition was performed, and one patient, who had arch and descending aortic aneurysm, underwent a hybrid intervention. Cardiopulmonary bypass (CPB) was administered via brachial artery cannulation.

Branches of the arcus aorta were anastomosed to the

Table 1. Clinical features of the patients with thoracic aortic aneurysms Patient Age Gender Interval

(years)

1

2

3

4

5

6

7

8

54

30

61

52

56

41

58

54

Clinical symptom

Male 30 yrs Hoarse voice

Female 11 yrs Back pain

Male 9 yrs Hoarse voice

Male 44 yrs Epigastric pain

Male 39 yrs Hoarse voice

Male 6 yrs Hoarse voice

Male 3 yrs Back pain

Male 18 days Hoarseness

and dysphagia

Type of Aneurysm aneurysm Diameter (mm) Saccular

Saccular

Saccular

Fusiform

Fusiform

Saccular

Saccular

Saccular

21x18

33x44

45x21

90

70

50x36

41x24

75

Etiology

Operation

Downfall TEVAR

Motor vehicle Left thoracotomy, accident greft interposition Motor vehicle TEVAR accident Motor Vehicle TEVAR accident Motor Vehicle Hybrid accident Tyre burst TEVAR

Downfall Thoracotomy,

graft interposition Motor vehicle Died accident preoperatively

Complication Type 1 endoleak None None None Exitus Brachial embolus None Exitus

Interval: Time between injury and treatment.

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Temmuz - July 2013

Thoracic aortic aneurysms after blunt trauma

Fig. 1. Preoperative digital subtraction angiography (DSA) and postoperative CTA of Patient 6 after successful TEVAR.

Dacron graft, which was placed in the ascending aorta.

Afterwards, the endovascular stent graft was placed in the proximal part of the arcus and descending aorta.

No complications were seen. He was transferred to the ward on the first postoperative day. One patient was lost on the postoperative fifth day due to sudden death.

We covered the subclavian artery in two patients.

During and after the procedure, follow-up was made with routine physical examination and Doppler ultrasonography (USG). We do not surgically intervene unless there are ischemic signs. These patients had no ischemic sign or loss of motor function at discharge or during the follow-up. One (Patient 6) had a left upper extremity ischemia due to an embolus after placing the endovascular stent. Embolectomy was performed and monophasic flow was administered.

Patient 1 had an endoleak at the first month followup, and TEVAR was repeated successfully. No paraplegia was seen. Femoral arteries were repaired with

Prolene sutures in TEVAR patients after the procedure and no ischemia was seen. Six patients were discharged from the hospital. Patient 6 had monophasic left upper extremity blood flow, documented with Doppler USG. Six other patients had no ischemic signs. Patient 8 had a history of a motor vehicle accident, 18 days before admission. He was diagnosed with saccular descending aortic aneurysm and urgent TEVAR was planned.

However, he suffered sudden cardiac arrest and was immediately transferred to the operating theater. Left thoracotomy was performed and rupture of the aneurysm was documented. Despite all attempts, he could not be saved.

Routine follow-up at the sixth month with CTA did not reveal any endoleaks. Aneurysmatic sacs were thrombosed. We did not observe aortic diameter increase in any of the patients. No ischemia was seen in the upper and lower extremities. Patientsâ&#x20AC;&#x2122; symptoms disappeared 15 days after the intervention on average.

Fig. 2. Preoperative and intraoperative images of Patient 5. After surgical rebranching, endovascular stent graft was placed into the arcus and descending aorta.

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Fig. 3. CTA image at the 6th month follow-up of Patient 4.

DISCUSSION Traumatic thoracic aortic injuries are uncommonbut highly lethal-injuries. Regardless of whether the injury is caused by blunt or penetrating trauma, the majority of the patients die immediately. Without appropriate treatment, up to 50% of the initial survivors will die within the first 72 hours.[1,4] In 1-2% of patients with traumatic aortic injury, the problem is not identified initially and they survive long enough to develop a chronic traumatic false aneurysm.[3,4] In 275 cases of traumatic aortic rupture reported by Parmley and colleagues,[4] 239 (88%) died during the first hour, 28 (10%) within two weeks, and others after 22, 50, and 76 days. Only five patients (2%) survived long enough to develop a chronic traumatic aneurysm.

Traumatic thoracic aortic injuries are usually located distal to the left subclavian artery.[5] Intercostal arteries, pleura and the ligamentum arteriosum fix the descending aorta more rigidly than the aortic arch and the heart during its course through the vertebral sulcus. During a horizontal deceleration trauma, the descending and other parts of the aorta move at different speeds. As a result, the isthmic part of the aorta is under maximum stress, and thus may yield total or partial rupture of the vessel. Direct loading of the pressurized descending thoracic aorta causes isthmus injury secondary to aortic wall strain. Deep medial lesions are common and could propagate soon after injury to form pseudoaneurysms.[6] Among the patients presented to our clinic, all but one had aneurysms distal to the subclavian artery (87.5%) and 75% were saccular. The interval between the trauma and diagnosis used in the literature to differentiate acute and chronic traumatic aortic injuries is not clear, varying between 36 hours and 3 months.[7,8] The interval between the trauma and diagnosis of a pseudoaneurysm may change. In a group of 10 patients operated for traumatic thoracic aortic aneurysms, Buket et al.[9] reported this period to 346

Fig. 4. Patient 2 after interpositioning of the Dacron graft to the descending aorta via left thoracotomy.

be between 1 day and 10 years. In our study, the most common symptom was hoarseness, and the mean interval between the injury and symptom was 19 years (range, 18 days-44 years).

In a literature review by Bennett and Cherry,[10] 104 chronic traumatic aortic aneurysms were identified; 50% of patients eventually developed symptoms, and 21% manifested radiological evidence of expansion.

Moreover, late rupture occurred in nine patients. In a similar study, Finkelmeier et al.[3] analyzed all the reported cases of chronic traumatic aneurysms between 1950 and 1980. Among 413 patients, 60 were followed without surgical intervention. The survival rates at 5 and 10 years in the unoperated patients were 70% and 65%, respectively. Of these, 20 (33%) died of aortic rupture or complications related to the chronic traumatic aneurysm.

TEVAR is a less invasive procedure than conventional surgery. Irace and colleagues[2] reported a series of 16 patients with chronic aortic aneurysm who underwent endovascular treatment. One mortality was reported due to disseminated intravascular coagulation.

They observed one type 1 endoleak. Demers and colleagues[1] lost one patient in a series of 15 patients with chronic aortic aneurysms treated with stent-grafts.

Caronno and colleagues[11] reported a series of 11 patients with intentional coverage of the left subclavian artery during stent-grafting of the thoracic aorta. They reported no related complications. In a series of 58 patients, Schoder et al.[12] overstented the left subclavian artery during TEVAR, and complete occlusion was seen in eight and partial occlusion in 24 patients. On the other hand, Caffarelli et al.[13] studied 53 patients who were identified as having blunt aortic injury. Of the 53 patients, 29 underwent planned, nonoperative management, and of these, in-hospital survival was 93%, with no aortic deaths in the remaining patients.

Temmuz - July 2013

Thoracic aortic aneurysms after blunt trauma

In our study, we used isolated TEVAR in five of our eight patients. One patient underwent a hybrid procedure. In the TEVAR group, we reported one brachial embolectomy, and one type 1 endoleak, requiring repeat TEVAR. Patients undergoing conventional surgery had no problems during the follow-ups. Patient 8 was diagnosed 18 days after a vehicle accident but died preoperatively due to the rupture of the aneurysm. He could have been saved if diagnosed at the first admission to the trauma center, which shows the importance of early diagnosis in these patients.

The limitations of our study are the small number of the patients, and the fact that, since patients that are subject of injury very rarely present to our department, we cannot give the percentage of aortic injury after trauma. Thirdly, none of our patients was assessed with CTA at the first admission after trauma, so we do not have any idea about the onset or course of the developing aneurysm.

In conclusion, chronic traumatic aneurysms have different anatomic characteristics than degenerative aneurysms; they are typically localized, calcified saccular lesions located just distal to the left subclavian artery.

Thoracic aortic aneurysms can be seen after blunt trauma. One to two percent of these patients, who injury is missed at the first admission, develop chronic false aneurysms.[3,4] These patients present with unspecific symptoms like cough, hoarseness, and epigastric and back pain months or even years after the accident.

We emphasize herein the importance of proper imaging, follow-up and diagnosis of aortic injury after blunt trauma, which can be managed successfully when diagnosed early. Especially in the late follow-up of these patients, the development of complications due to aneurysms after blunt aortic trauma should be considered.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Demers P, Miller C, Scott Mitchell R, Kee ST, Lynn Cha-

Cilt - Vol. 19 Sayı - No. 4

gonjian RN, Dake MD. Chronic traumatic aneurysms of the descending thoracic aorta: mid-term results of endovascular repair using first and second-generation stent-grafts. Eur J Cardiothorac Surg 2004;25:394-400.

2. Irace L, Laurito A, Venosi S, Irace FG, Malay A, Gossetti B, et al. Mid- and long-term results of endovascular treatment in thoracic aorta blunt trauma. ScientificWorldJournal 2012;2012:396873.

3. Finkelmeier BA, Mentzer RM Jr, Kaiser DL, Tegtmeyer CJ, Nolan SP. Chronic traumatic thoracic aneurysm. Influence of operative treatment on natural history: an analysis of reported cases, 1950-1980. J Thorac Cardiovasc Surg 1982;84:25766.

4. Parmley LF, Mattingly TW, Manion WC, Jahnke EJ Jr. Nonpenetrating traumatic injury of the aorta. Circulation 1958;17:1086-101.

5. Yilmaz O, Arbatli H, Sirin G, Arpaz M, Yagan NE, Numan F, et al. Endovascular treatment of traumatic thoracic aortic aneurysms: report of five cases and review of the literature.

Ulus Travma Acil Cerrahi Derg 2010;16:575-8.

6. Schmoker JD, Lee CH, Taylor RG, Chung A, Trombley L, Hardin N, et al. A novel model of blunt thoracic aortic injury: a mechanism confirmed? J Trauma 2008;64:923-31.

7. Kato N, Dake MD, Miller DC, Semba CP, Mitchell RS, Razavi MK, et al. Traumatic thoracic aortic aneurysm: treatment with endovascular stent-grafts. Radiology 1997;205:657-62.

8. Rousseau H, Soula P, Perreault P, Bui B, Janne d’Othée B, Massabuau P, et al. Delayed treatment of traumatic rupture of the thoracic aorta with endoluminal covered stent. Circulation 1999;99:498-504.

9. Buket S, Yağdı T, Çıkrıkçıoğlu M. Aortanın travmatik lezyonları. İçinde: Buket S, Yağdı T, editör. Aort cerrahisi. İstanbul: Yüce Reklam Yayım Dağıtım A.Ş.; 2003. s. 40537.

10. Bennett DE, Cherry JK. The natural history of traumatic aneurysms of the aorta. Surgery 1967;61:516-23.

11. Caronno R, Piffaretti G, Tozzi M, Lomazzi C, Rivolta N, Castelli P. Intentional coverage of the left subclavian artery during endovascular stent graft repair for thoracic aortic disease. Surg Endosc 2006;20:915-8.

12. Schoder M, Grabenwöger M, Hölzenbein T, Cejna M, Ehrlich MP, Rand T, et al. Endovascular repair of the thoracic aorta necessitating anchoring of the stent graft across the arch vessels. J Thorac Cardiovasc Surg 2006;131:380-7.

13. Caffarelli AD, Mallidi HR, Maggio PM, Spain DA, Miller DC, Mitchell RS. Early outcomes of deliberate nonoperative management for blunt thoracic aortic injury in trauma. J Thorac Cardiovasc Surg 2010;140:598-605.

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Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):348-356

Original Article

Klinik Çalışma doi: 10.5505/tjtes.2013.56313

Fractures of the mandible: a 20-year retrospective analysis of 753 patients Mandibula kırıkları: 753 hastanın 20 yıllık geriye dönük değerlendirmesi Teoman ESKİTAŞCIOĞLU, İrfan ÖZYAZGAN, Atilla ÇORUH, Galip Kemali GÜNAY, Yalçın YONTAR, Mehmet ALTIPARMAK BACKGROUND

AMAÇ

The craniofacial region is one of the most frequently injured parts of the body, and mandibular fracture is one of the commonest facial skeletal injuries. The most frequent causes of mandibular fractures are the traumas related to traffic accidents, falls, interpersonal violence, and sports activities, etc.

Kranyofasiyal bölge vücudun en sık yaralanan bölümlerinden biridir ve yüz bölgesindeki kemik yapısından dolayı mandibula kırıkları yüz yaralanmalarında sık görülür. Mandibula kırıkları en sık travmaya bağlı görülür ve bu kırıklar ile trafik kazaları, düşme, kişiler arası şiddet, spor aktiviteleri ilişkilidir.

METHODS

Seven hundred fifty-three cases (615 male, 138 female; megan age 36.2 years) (age >16) with mandibular fracture were evaluated retrospectively. Patient records were examined in terms of age, sex, etiology, seasonal variation, fracture localization, accompanying traumas, treatment modality, and postoperative complications.

GEREÇ VE YÖNTEM

RESULTS

BULGULAR

Traffic accidents were the most common etiologic cause in all age groups and both sexes. All cases had a total of 1090 fractures, and the most common fracture localization was the parasymphysis (28.6%), followed by the condyle, corpus, angulus, symphysis, dentoalveolar process, ramus, and coronoid process, respectively. In 25 (3.3%) patients with fissurelike, non-displaced fracture, only symptomatic treatment was applied. Closed reduction with elastic bandage, arch bar, quick-fix screws or Ivy Loop was the only method performed in 280 (37.2%) patients. Osteosynthesis by open reduction and internal fixation (miniplates, screws or transosseous wiring) was performed in 403 (53.5%) patients; closed reduction techniques were also performed in 134 of these patients.

CONCLUSION

In the recent years, double-road constructions, increased traffic audits and regulation of the traffic rules decreased the incidence of mandibular fractures.

Geriye dönük olarak 753 hastada (615 erkek, 138 kadın; ortalama yaş 36,2 yıl) (>16 yaş) mandibula kırıkları değerlendirildi. Hastalar yaş, cinsiyet, etyoloji, mevsimsel değişim, kırık yeri, eşlik eden travmalar, tedavi yöntemi ve ameliyat sonrası komplikasyonlar açısından incelendi.

Trafik kazaları tüm yaş gruplarında ve her iki cinste de en sık etyolojik neden idi. Tüm olgularda toplam 1090 kırık vardı en sık kırık lokalizasyonu parasimfizer bölge idi (%28,6), bunu sırasıyla kondil, korpus, angulus, simfizis, dentoalveolar, ramus ve koronoid kırıkları izlemekteydi.

Kırık hatları nondeplese olan 25 (%3.3) hastaya semptomatik tedavi uygulandı. Elastik bandaj, arch bar, Ivy Loop, quick fix vida ile 280 hastada kapalı redüksiyon uygulandı. Açık redüksiyon ve internal tespit (miniplak, vida veya transosseöz kablo) ile osteosentez 403 (%53,5) hasta üzerinde uygulandı. Bu hastaların 134’ünde kapalı redüksiyon gerçekleştirildi.

SONUÇ

Son yıllarda, çift yol inşaatları, artan trafik denetimleri ve trafik kurallarına düzenlenmesiyle mandibula kırıklarının insidansı azalmıştır.

Key Words: Etiology; mandibular fractures; maxillofacial trauma.

Anahtar Sözcükler: Etyoloji; mandibula kırıkları; maksillofasial travma.

Department of Plastic Reconstuctive and Aesthetic Surgery, Erciyes University Faculty of Medicine, Kayseri, Turkey.

Erciyes Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, Kayseri.

Correspondence (İletişim): Teoman Eskitaşcıoğlu, M.D. Erciyes Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, Melikgazi 38039 Kayseri, Turkey.

Tel: +90 - 352 - 207 66 66 e-mail (e-posta): teskitascioglu@gmail.com

348

MATERIALS AND METHODS In our previous report[15] of pediatric mandibular fractures, the age of the patients ranged from 0 to 16 years. For this reason, the present report was conducted on patients who were over the age of 16 years. The treatment of the patients was performed between January 1992 and December 2011. The data of the patients regarding age, sex, etiology, seasonal variation, fracture localization, accompanying traumas, treatment modality, and postoperative complications were collected in a database program (FileMaker Pro, version 10.0, File-Maker Inc, Santa Clara, CA). Clustered data were analyzed statistically using the Statistical Package for the Social Sciences (SPSS) for Windows (version 20.0.0, SPSS, Inc., Chicago, IL).

RESULTS Age and sex There were 615 (81.7%) male and 138 (18.3%) female patients, with a male to female ratio of 4.4:1.

The age of the patients ranged from 17 to 90 years, and the mean age (± SD) was 36.2 (± 16.3) years. In both sexes, the highest incidence of mandibular fractures (n=367, 48.7%) was observed in the age group of 17-30 years, and the most frequently affected patients were males in this age group (n=301, 40.0%) (Fig. 1).

Etiology All of the fractures treated in our department were traumatic fractures of the mandible. Traffic accidents Cilt - Vol. 19 Sayı - No. 4

200 100 0

17-30

31-40

41-50

>60

Fig. 1. Distribution of patients according to age and sex.

No. of patients

The Department of Plastic and Reconstructive Surgery of Erciyes University Medical Faculty is situated in Central Anatolia, and since 1987, has been the only department responsible for the oral and maxillofacial trauma care of a population of nearly 10 million, in Kayseri and the surrounding area. In this series, it was aimed to retrospectively analyze mandibular fractures of patients (≥17 years) who referred to our department and to compare this data with the literature.

Female Male

300

Age

125 100 75 50 25 0

1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th 12th Months

Fig. 2. Monthly distribution of patients.

No. of patients

The craniofacial region is one of the most frequently injured parts of the body, and mandibular fracture is one of the commonest facial skeletal injuries[1-4] due to certain structural properties of the bone. Mandibular fractures are divided into two main groups according to etiology as pathologic or traumatic fractures. Tumors, osteoporosis and diseases that affect the bony structure directly/indirectly appear as the causes of pathologic fractures. However, the most frequent causes of mandibular fractures are traumas related to traffic accidents, falls, interpersonal violence, and sport activities, etc.[5] Traffic accidents are the most common cause of mandibular fractures in developing countries,[2,5-9] as well as in Turkey,[3] whereas interpersonal violence is the major causative factor in developed countries.[10-14]

No. of patients

Fractures of the mandible

125 100 75 50 25 0

92

94

96

98 00 02 Years

04

06

08

10

Fig. 3. Yearly distribution of patients.

were the primary causative factor of mandibular fractures in all age groups and both sexes. While the overall ratio of traffic accidents was 54.3%, 38.2% occurred as a result of in-vehicle accidents, 8.8% were due to pedestrian accidents and 7.3% to motorcycle-related accidents. The other causes of mandibular fractures were assault, falls, industrial injuries, gunshot injuries, and others (include sporting and animal-related injuries).

All of the causative factors accounted for the highest number in the age group of 17-30 years. Motorcyclerelated injuries, industrial injuries, and etiologies including violence, such as assault and gunshot injuries, were most commonly observed among male patients.

Among females, only one patient had trauma due to motorcycle-related injury and none had trauma due to gunshot injury (Tables 1, 2). In motorcycle-related injuries, 98% of the patients were male and 59.2% were aged 17-30 years. These rates were 90.6% and 58.6% in industrial injuries and 100% and 68.7% in gunshot injuries, respectively.

Monthly and yearly distribution Figure 2 shows the monthly distribution of mandibular fracture admissions to our department between January 1992 and December 2011. The highest pro349

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Table 1. Etiology of mandibular fractures according to sex and male/female ratio Mechanism of injury

Male

Female

n %

Traffic accident In-vehicle Pedestrian Motorcycle Assault Falls Industrial injury Gunshot injury Others Total

222 50 54 129 107 29 16 8 615

36.1 8.1 8.8 21.0 17.4 4.7 2.6 1.3 100.0

Total

n % 66 16 1 14 35 3 0 3 138

47.8 11.6 0.7 10.1 25.4 2.2 0.0 2.2 100.0

Male/Female

n % 288 66 55 143 142 32 16 11 753

38.2 8.8 7.3 19.0 18.8 4.3 2.1 1.5 100

1/1.32 1/1.43 1/0.08 1/0.5 1/1.46 1/0.47 1/0 1/1.7

Table 2. Etiology of mandibular fractures according to age category (years) Mechanism of

injury

Traffic accident In-vehicle Pedestrian Motorcycle Assault Falls Industrial injury Gunshot injury Others Total

17-30

31-40

41-50

51-60

>60

Total

n % n % n % n % n % n % 137 37.3 29 7.9 33 9.0 69 18.8 64 17.4 18 4.9 11 3.0 6 1.6 367 100.0

62 43.7 13 9.2 8 5.6 30 21.1 19 13.4 8 5.6 1 0.7 1 0.7 142 100.0

43 44.8 7 7.3 8 8.3 14 14.6 18 18.8 2 2.1 3 3.1 1 1.0 96 100.0

26 32.1 10 12.3 3 3.7 11 13.6 27 33.3 2 2.5 1 1.2 1 1.2 81 100.0

20 7 3 19 14 2 0 2 67

29.9 10.4 4.5 28.4 20.9 3.0 0.0 3.0 100.0

288 66 55 143 142 32 16 11 753

38.2 8.8 7.3 19.0 18.9 4.2 2.1 1.5 100.0

Table 3. Anatomic sites of fractures according to age category (years) Localization

Parasymphysis Condyle Corpus Angulus Symphysis DAP Ramus Coronoid process Total

17-30

31-40

41-50

51-60

>60

Total

n % n % n % n % n % n % 160 29.1 116 21.1 97 17.7 100 18.2 40 7.3 24 4.4 9 1.6 3 0.5 549 100.0

63 31.9 33 16.7 44 22.3 30 15.2 12 6 12 6 3 1.5 0 0 197 100.0

27 30 28 21 13 9 8 1 137

19.7 21.9 20.4 15.3 9.5 6.6 5.8 0.7 100.0

34 25 20 13 8 6 3 0 109

31.2 22.9 18.3 11.9 7.3 5.5 2.8 0 100.0

28 11 26 18 7 4 4 0 98

28.3 312 11.1 215 26.3 215 18.2 182 7.1 80 4 55 4 27 0 4 100.0 1090

28.6 19.7 19.7 16.7 7.3 5.1 2.5 0.4 100.0

DAP: Dentoalveolar process.

portion was seen in summer (33.7%), followed by autumn (29.2%), spring (21.5%) and winter (15.6%). The highest incidence of mandibular fractures was seen during July, August and September (12.7%, 11.8% and 11.3%, respectively). The fewest hospital admissions due to mandibular fracture were seen in December and February (5.6% and 3.9%, respectively). Figure 350

3 shows the yearly distribution of admissions to our department. The highest number of admitted patients was in 2001 (7.4%) and the lowest in 2011 (1.3%).

Fracture Localizations and Patterns Because some patients had more than one mandibular fracture line, 753 patients showed 1090 fractures, Temmuz - July 2013

Fractures of the mandible

Table 4. Anatomic sites of fractures according to sex and male/female ratio Localization

Male

Female

n %

Parasymphysis Condyle Corpus Angulus Symphysis Dentoalveolar process Ramus Coronoid process Total

254 185 166 157 64 45 21 4 896

28.3 20.7 18.5 17.5 7.1 5.1 2.4 0.4 100.0

Total

n % 58 30 49 25 16 10 6 0 194

29.9 15.5 25.2 12.9 8.2 5.2 3.1 0 100.0

Male/Female

n % 312 215 215 182 80 55 27 4 1090

28.6 19.7 19.7 16.7 7.3 5.1 2.5 0.4 100.0

1/1.05 1/0.75 1/1.36 1/0.74 1/0 1/1.02 1/1.29 1/0

Table 5. Distribution of fracture pattern according to age category (years) Pattern

Unilateral single fracture Unilateral multiple fracture Bilateral multiple fracture Total

17-30

31-40

41-50

51-60

>60

Total

n % n % n % n % n % n % 208

56.7

88

45 12.2

114 31.1

367 100.0

62.0

22 15.5

32 22.5

142 100.0

61

63.5

53

65.4

38

56.7

448 59.5

14 14.6

21 21.9

96 100.0

13

16.1

6

9.0

100 13.3

15

18.5

23

34.3

205 27.2

81 100.0

67

100.0

753 100.0

Table 6. Distribution of fracture pattern according to sex and male/female ratio Pattern

Unilateral single fracture Unilateral multiple fracture Bilateral multiple fracture Total

Male n % 362 84 169 615

58.9 13.7 27.4 100.0

averaging 1.45 fractures per mandible. In both sexes and all age groups, the most affected site of the mandible was the parasymphysis (Tables 3, 4), followed respectively by the condyle and corpus below the age of 50 years and the corpus and condyle above the age of 50 years, respectively (Figs. 4, 5).

There was only a single fracture line in 448 (59.5%), unilateral multiple fracture lines in 100 (13.3%) and bilateral multiple fracture lines in 205 (27.2%) patients.

Regarding the distribution of fracture patterns beyond age groups and sexes, unilateral single fracture pattern had the highest incidence (Tables 5, 6). The most common fracture localization was the parasymphysis (134/448) followed by the corpus (103/448) in single fractured patients (Table 7). Condyle + symphysis Cilt - Vol. 19 Say覺 - No. 4

Female n % 86 16 36 138

62.3 11.6 26.1 100.0

Total

Male/Female

n % 448 100 205 753

59.5 13.3 27.2 100.0

1/1.06 1/0.85 1/0.95

(16/100) in unilateral multiple fractures and parasymphysis + condyle (43/205) in bilateral multiple fractures were the most common combinations (Tables 8, 9). Twenty-nine patients displayed 3 fracture lines (2.8%) and 7 patients displayed 4 fracture lines (0.9%).

The mandibular fractures caused by traffic accidents were most commonly localized at the parasymphysis and corpus, whereas fractures caused by falls were at the parasymphysis and condyle and those caused by assault were at the parasymphysis and angulus (Fig. 6). Thirty-four patients (4.5%) had a mandibular fracture line that opened to the oral mucosa.

Accompanying Traumas Although 80.2% (n=604) of the patients had isolated mandibular fracture, 19.8% (n=149) had accom351

Ulus Travma Acil Cerrahi Derg

Condyle (20.3%)

Coronoid process (0.5%)

Ramus (2.2%) DAP (5.1%)

Symphysis (7.4%)

Angulus (17.1%) Corpus (19.1%)

Parasymphysis (28.3%)

Fig. 4. Distribution of fracture localizations below the age of 50. (Color figure can be viewed in the online issue, which is available at www.tjtes.org).

Condyle (17.4%)

Ramus (3.4%)

Angulus (15%) Corpus (22.2%)

Localization

n 134 103 78 68 40 13 11 1 448

Symphysis (7.2%)

Parasymphysis (30%)

Fig. 5. Distribution of fracture localizations above the age of 50. (Color figure can be viewed in the online issue, which is available at www.tjtes.org).

panying fractures in the other facial bones. As several patients had more than one injury, 149 patients showed 155 facial fractures. The most common associated facial fracture was the zygomatic fracture followed by Le Fort fractures (Table 10).

Two hundred and seventy-one (36%) patients showed 389 accompanying injuries of other systems.

Cranial injuries were the most common, followed by orthopedic, thoracal and intraabdominal injuries, respectively (Table 11). Twenty-eight patients (3.7%) who had accompanying cranial and other system injuries exhibited a mortal course.

Treatment Method and Period We could not apply follow-up and treatment in 45 (6%) patients due to mortal course (n=28) or refusal of treatment (n=17). In 25 (3.3%) patients with fissurelike, non-displaced fracture, no reduction technique was applied. These patients underwent a symptomatic treatment consisting of analgesics, oral rinse and soft diet. Closed reduction with elastic bandage, arch bar, quick-fix screws, or Ivy Loop was the only method 352

Table 7. Anatomic localizations of single fractures in 448 patients Parasymphysis Corpus Condyle Angulus Symphysis Dentoalveolar process Ramus Coronoid process Total

Coronoid process (0%)

DAP (4.8%)

performed in 280 (37.2%) patients. Osteosynthesis by open reduction and internal fixation (miniplates, screws or transosseous wiring) was performed on 403 (53.5%) patients; closed reduction techniques were also carried out in 134 of these patients. The distribution of the treatment methods shows that open reduction and internal fixation with or without closed reduction was the most common technique used for all the patients (Table 12). 54.3% of the patients who underwent a reduction technique (CR, OR or OR+CR) were

Table 8. Anatomic localizations of unilateral multiple fractures in 100 patients Localization

n

Condyle+symphysis Parasymphysis+dentoalveolar process Corpus+angulus Parasymphysis+condyle Symphysis+dentoalveolar process Parasymphysis+angulus Parasymphysis+symphysis Condyle+corpus Corpus+dentoalveolar process Condyle+angulus Condyle+dentoalveolar process Corpus+symphysis+dentoalveolar process Angulus+symphysis Parasymphysis+corpus Parasymphysis+symphysis+dentoalveolar process Symphysis+ramus Angulus+corpus Angulus+ramus Condyle+corpus+dentoalveolar process Condyle+symphysis+dentoalveolar process Corpus+symphysis Parasymphysis+angulus+dentoalveolar process Parasymphysis+corpus+ram+dentoalveolar process Symphysis+angulus Total

16 13 8 7 7 6 6 5 5 4 4 3 2 2 2 2 1 1 1 1 1 1 1 1 100

Temmuz - July 2013

Fractures of the mandible

Table 9. Anatomic localizations of bilateral multiple fractures in 235 patients Localization Parasymphysis+condyle Parasymphysis+angulus Corpus+angulus Condyle+corpus Bilateral corpus Bilateral parasymphysis Parasymphysis+corpus Bilateral angulus Condyle+angulus Parasymphysis+ramus Symphysis+bilateral condyle Corpus+ramus Bilateral condyle Condyle+bilateral parasymphysis Parasymphysis+angulus+ramus Parasymphysis+bilateral angulus Angulus+bilateral parasymphysis Angulus+corpus Angulus+ramus Symphysis+bilateral condyle Symphysis+coronoid process+bilateral condyle DAP Condyle+angulus+ramus Condyle+bilateral corpus Condyle+corpus+angulus Condyle+corpus+ramus Condyle+symphysis Corpus+bilateral angulus Parasymphysis+bilateral condyle Parasymphysis+DAP+bilateral condyle Parasymphysis+condyle+angulus Parasymphysis+condyle+coronoid process+DAP Parasymphysis+condyle+corpus Parasymphysis+condyle+corpus+DAP Parasymphysis+coronoid process Parasymphysis+coronoid process+bilateral condyle Parasymphysis+symphysis+bilateral condyle Symphysis+bilateral parasymphysis Total

n 43 36 22 15 13 13 10 6 6 4 4 3 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 205

DAP: Dentoalveolar process.

treated within the first day, 25.2% between the 2nd4th days, 10% between the 5th-7th days, and 10.5% in more than 7 days (Fig. 7).

Complications Sixty-one (8.1%) patients showed postoperative complications. Complications, in decreasing order of frequency, included occlusion disorder, plate exposition and infection, sensory complications (hypoesthesia, paresthesia), opening at the mucosal sutures, and temporomandibular joint dysfunction. There was Cilt - Vol. 19 Say覺 - No. 4

no complication among the patients who were treated conservatively. Regarding reduction techniques, the lowest complication rates were observed among patients who underwent closed reduction alone (9/280) and the highest in patients subjected to both open and closed reduction (30/134) (Table 13).

DISCUSSION Despite being the heaviest and strongest bone of the face, fracture of the mandible is one of the commonest facial skeletal injuries for the following reasons: 1) It is an open arch; 2) It is located in the lower portion of the face; 3) It is the mechanism of hyperextension and hyperflexion of the head in traffic accidents; and 4) It atrophies as a result of aging.[16] The primary causative factor of mandibular fractures in developing countries is traffic accidents,[2,3,5-9] whereas interpersonal violence is the major cause of this trauma in developed countries.[10-14] In the literature, there are some reports from developed countries[4,17] indicating traffic accidents as the most frequent cause of mandibular injury.

Poor roads and inadequate enforcement of road safety regulations and speed limits are some of the factors that have accounted for the higher incidence of traffic accidents in developing countries.[7] James et al.[18] explained that epidemiologic factors in mandibular fractures had changed with the advent of lower speed limits, seatbelt and helmet laws, and increased urban violence. In the present report conducted in a developing country, Turkey, traffic accidents were the primary causative factor of mandibular fractures in both sexes and in all age groups. The results of the present report Table 10. Distribution of additional maxillofacial

trauma Localization Zygoma Maxillary dentoalveolar process Nasal bone Nasoorbitoethmoid Le Fort I-III Frontal sinus Panfacial Total

n 63 10 7 3 57 3 12 155

Table 11. Distribution of additional traumas of other systems Localization n Cranial Orthopedic Thoracal Intraabdominal Total

154 137 64 34 289 353

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Table 12. Management of mandibular fractures

Conservative

Arch bar

Quick-fix

Ivy Loop

Elastic bandage

With CR

Without CR

Exitus

Rejection

25 3.3

267 35.5

3 0.4

4 0.5

6 0.8

134 17.8

269 35.7

28 3.7

17 2.3

n %

CR (n=280)

OR (n=403)

Not treated (n=45)

Total

753 100

CR: Closed reduction; OR: Open reduction.

Table 13. Distribution of postoperative complications according treatment method

Treatment

Complication

Closed reduction Open reduction Open reduction+Closed reduction Total

Malocclusion Temporomandibular joint dysfunction Exposition of plate Infection Opening mucosal sutures Sensory complications Total

7 - - 2 - - 9

are in agreement with the previous reports regarding age and sex. There was a predominance of male patients over females, with a ratio of 4.4:1, and it was similar to the reported overall ratios that have ranged between 2.9:1 and 5:1.[5-9,12,13,17] The most affected patients were males aged 17-30 years (n=301, 40%), which is in agreement with the literature.[5-9,13] Motorcycle-related injuries, industrial injuries and etiologies including violence, such as assault and gunshot injuries, were most commonly observed in male patients aged 17-30 years. The explanation may be that males in this age group are most likely to be involved in violence, and they also drive vehicles carelessly and participate in dangerous exercises and sports.[8] Moreover, according to the distribution of cases by months, mandibular fractures exhibited a considerable increase during the summer (July, August, September). Because Turkish families prefer the summer months for their

50

Parasimfizer

Condyle

Corpus

3 2 3 4 3 7 22

7 1 10 7 2 3 30

17 3 13 13 5 10 61

holidays, thereby causing traffic congestion, the incidence of traffic accidents soars during that period.[15] Similar to the previous reports[5-8] (range, 45.3-64.3%), there was only a single fracture line in 448 patients (59.5%), while 305 patients (40.5%) had more than one fracture line. Many authors reported the condyle as the most frequently affected site,[2,4,9,10,17] whereas others reported this to be the parasymphysis[3,5,7,12] and angulus.[8,19] The most affected sites of the mandible in the present report below the age of 50 years werre the parasymphysis, condyle and corpus, whereas these were the parasymphysis, corpus and condyle, respectively, above the age of 50 years. Similar to a previous report,[7] the most common combination of fracture site was the parasymphysis and condyle. In this report, it was observed that fractures of the anterior region of the mandible (parasymphysis and symphysis) were likely to be combined with fractures of the posterior ◆

Angulus

40 %

30

11.3

20

◆

10 0

1st Traffic acc.

Fall

Assault

Fig. 6. Distribution of fracture localizations according to etiology.

354

2nd

10.5

7.3

6.6

4.2

2.4

3.4

◆

◆

◆

◆

◆

3rd

4th 5th Days

6th

7th

◆ >7

Fig. 7. Distribution of patients according to treatment period.

Temmuz - July 2013

Fractures of the mandible

region, the condyle and angulus. A correlation between the mechanism of injury and fracture localization was shown in the present report. Particularly in agreement with the report of Atilgan et al.,[20] the most affected regions of the mandible were the parasymphysis and corpus due to traffic accidents, the parasymphysis and condyle due to falls, and the parasymphysis and angulus due to assault (Fig. 6). Individuals involved in motor vehicle collisions present to emergency departments with a variety of associated injuries.[21] Although 80.2% (n=604) of the patients had isolated mandibular fracture, 19.8% (n=149) had accompanying fractures of other facial bones, especially zygomatic and Le Fort I-III. In the literature,[5-9,12] the incidence of accompanying facial fractures ranged from 5-30%.

Furthermore, 271 patients (36%) had accompanying traumas of other systems. The leading accompanying additional trauma was cranial injury.

In the present report, open reduction and internal fixation with miniplates, screws or transosseous wiring (n=403, 53.5%) was the most frequently applied method for the treatment of the mandibular fractures.

54.3% of the patients who underwent a certain reduction technique were treated within the first day. The time between the injury and surgery depends on factors such as good clinical condition to tolerate a surgical procedure and the admission time of the patient.

Hermund et al.[22] showed that there is presently no strong evidence for either acute or delayed treatment of mandibular fractures in order to minimize postoperative complications. A postoperative complication rate of 8.1% was observed in the present report. The highest complication rates were observed among patients who underwent both open and closed reduction. The most common complication was malocclusion followed by plate exposition and infection, respectively.

The incidence of postoperative infection was 1.7%, and this was definitively lower than the data reported previously.[2,5,6,9,13] In conclusion, in this clinical series, the most frequently affected patients were males aged 17-30 years, and the most affected site of the mandible was the parasymphysis. The most common causative factor of mandibular fracture was motor vehicle accidents.

However, in recent years, increased double-road construction, traffic audits and regulation of the traffic rules have decreased the incidence of mandibular fractures.

Conflict-of-interest issues regarding the authorship or article: None declared.

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Int J Oral Maxillofac Surg 2010;39:10-5.

10. Iida S, Hassfeld S, Reuther T, Schweigert HG, Haag C, Klein J, et al. Maxillofacial fractures resulting from falls. J Craniomaxillofac Surg 2003;31:278-83.

11. Rocton S, Chaine A, Ernenwein D, Bertolus C, Rigolet A, Bertrand JC, et al. Mandibular fractures: epidemiology, therapeutic management, and complications in a series of 563 cases. Rev Stomatol Chir Maxillofac 2007;108:3-12.

12. Czerwinski M, Parker WL, Chehade A, Williams HB. Identification of mandibular fracture epidemiology in Canada: Enhancing injury prevention and patient evaluation. Can J Plast Surg 2008;16:36-40.

13. Sojot AJ, Meisami T, Sandor GK, Clokie CM. The epidemiology of mandibular fractures treated at the Toronto general hospital: A review of 246 cases. J Can Dent Assoc 2001;67:640-4.

14. Erdmann D, Follmar KE, Debruijn M, Bruno AD, Jung SH, Edelman D, et al. A retrospective analysis of facial fracture etiologies. Ann Plast Surg 2008;60:398-403.

15. Eskitascioglu T, Ozyazgan I, Coruh A, Gunay GK, Yuksel E. Retrospective analysis of two hundred thirty-five pediatric mandibular fracture cases. Ann Plast Surg 2009;63:52230.

16. Holt RG. Maxillofacial trauma. In: Otolaryngology head and neck surgery. Mosby Company; 1986. p. 313-4.

17. Bormann KH, Wild S, Gellrich NC, Kokemüller H, Stühmer C, Schmelzeisen R, et al. Five-year retrospective study of mandibular fractures in Freiburg, Germany: incidence, etiology, treatment, and complications. J Oral Maxillofac Surg 2009;67:1251-5.

18. James RB, Fredrickson C, Kent JN. Prospective study of mandibular fractures. J Oral Surg 1981;39:275-81.

19. Olson RA, Fonseca RJ, Zeitler DL, Osbon DB. Fractures of the mandible: a review of 580 cases. J Oral Maxillofac Surg 1982;40:23-8.

20. Atilgan S, Erol B, Yaman F, Yilmaz N, Ucan MC. Mandibu355

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lar fractures: a comparative analysis between young and adult patients in the southeast region of Turkey. J Appl Oral Sci 2010;18:17-22.

21. Fischer K, Zhang F, Angel MF, Lineaweaver WC. Injuries associated with mandible fractures sustained in motor ve-

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hicle collisions. Plast Reconstr Surg 2001;108:328-31.

22. Hermund NU, Hillerup S, Kofod T, Schwartz O, Andreasen JO. Effect of early or delayed treatment upon healing of mandibular fractures: a systematic literature review. Dent Traumatol 2008;24:22-6.

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Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):357-362

Original Article

Klinik Çalışma doi: 10.5505/tjtes.2013.99810

Demographic and etiologic characteristics of children with traumatic serious hyphema Çocuklarda travmatik ciddi hifemalarda demografik ve etyolojik özellikler Fatih Mehmet TÜRKCÜ, Harun YÜKSEL, Alparslan ŞAHİN, Kürşat CİNGÜ, Şeyhmus ARI, Yasin ÇINAR, Muhammed ŞAHİN, Adnan YILDIRIM, İhsan ÇAÇA

BACKGROUND

AMAÇ

We aimed to evaluate the etiologic factors, complications, follow-up, and treatment outcomes in serious hyphema following blunt ocular trauma in childhood.

Çocuk yaş grubunda künt göz travmaları sonrası oluşan ciddi hifemalarda etyolojik faktörler, oluşan komplikasyonlar, takip ve tedavi sonuçları değerlendirildi.

METHODS

GEREÇ VE YÖNTEM

The medical records of 136 patients diagnosed as grade 3 or 4 hyphema due to blunt ocular trauma between January 2006 and December 2011 were evaluated. Visual acuity (VA), complications, and medical and surgical treatments were analyzed. Factors affecting visual prognosis were compared in grade 3 and 4 hyphema cases.

RESULTS

The mean age of patients was 9.7±4 years. Etiologic factors for trauma were stone in 53 (39%), bead bullet in 25 (18.4%) and others in 58 (42.6%) patients. The most common complication of grade 3 and 4 hyphema was traumatic mydriasis (19.1%), followed by cataract (9.6%) and glaucoma (5.1%). Medical treatment was successful in 114 (83.8%) patients, and 22 (16.2%) patients underwent surgery. Mean initial and final VA of grade 4 patients were found to be significantly lower than those of grade 3 patients.

CONCLUSION

Ocak 2006 ile Aralık 2011 yılları arasında künt göz travması nedeni ile evre 3 ve 4 hifema tanısı alan ve tedavisi yapılmış 136 hastanın dosyası geriye dönük olarak incelendi. Görme keskinliği (GK), gözlenen komplikasyonlar, uygulanan medikal ve cerrahi tedaviler kaydedildi. Evre 3 ve 4 olgularda görme prognozu üzerinde etkili faktörler ve tedavi sonuçları karşılaştırıldı.

BULGULAR

Hastaların yaş ortalamaları 9,7±4 yıl idi. Travmaya sebep olan etyolojik faktörler sırası ile taş çarpması 53 (%39), boncuk mermisi 25 (%18,4) ve diğer faktörler 58 (%42,6) oluşturmakta idi. Evre 3 ve 4 hifemanın en sık komplikasyonu travmatik midriyazis (%19,1) iken bunu katarakt (%9,6) ve glokom (%5,1) izlemekteydi. İlaç tedavisi 114 (%83,8) olguda başarılı olurken, 22 (%16,2) olguda cerrahi gerekti. İlk ve son GK evre 4 olgularda evre 3’lere göre belirgin olarak daha düşüktü.

SONUÇ

In grade 3 and 4 hyphema due to blunt trauma, visual prognosis worsened in the presence of additional ocular pathologies. Considering the bad visual prognosis of severe hyphema patients, prompt treatment and close follow-up may prevent complications resulting in poor VA.

Künt travma nedeni ile hifema gelişen evre 3 ve 4 olgularda ilave göz patolojileri nedeni ile görme prognozu olumsuz etkilenebilmektedir. Ciddi hifemalı olgularda görme prognozundaki olumsuz seyir göz önüne alınarak bu hastaların yakın takibi ve tedavisi oluşabilecek komplikasyonların kalıcı etkilerini önleyebilecektir.

Key Words: Blunt trauma; children; hyphema; visual prognosis.

Anahtar Sözcükler: Künt travma; çocuk; hifema; görme prognozu.

Presented at the 46th National Congress of Ophthalmology Society (October 17-21, 2012, Antalya Turkey).

Department of Ophthalmology, Dicle University Faculty of Medicine, Diyarbakir, Turkey.

TOD 46. Ulusal Kongresi'nde sunulmuştur (17-21 Ekim 2012, Antalya).

Dicle Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, Diyarbakır.

Correspondence (İletişim): Fatih Mehmet Türkcü, M.D. Dicle Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, 21100 Diyarbakır, Turkey.

Tel: +90 - 412 - 248 80 01 e-mail (e-posta): turkcufm@gmail.com

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Hyphema is the presence of red blood cells in the anterior chamber of the eye.[1] Since the most common causes are blunt or penetrating ocular trauma, it may also develop following surgeries, or can occur spontaneously related to some systemic disorders.[1-3] In addition to congenital causes, the most common cause of unilateral blindness in childhood is ocular trauma.

[4] Ocular trauma is more common in developing countries, and blunt trauma often leads to hyphema.[5] Sudden compression and distortion of ocular structures following contusion has been considered the main reason associated with the development of hyphema. Anterior chamber bleeding occurs as a result of a ruptured vessel in the peripheral iris and anterior ciliary body due to stretching of limbal tissues.[6,7] The majority of patients with hyphema can be treated without any ocular complications. Accompanying complications such as increased intraocular pressure (IOP), re-bleeding, corneal blood staining, cataract, intravitreal hemorrhage, choroid rupture, sphincter tear, and iridodialysis may affect the visual prognosis.[1,2,7-9] The main causes of increased IOP are angle obstruction with blood cells, posterior synechia formation and angle recession.[10] Apart from complications of traumatic hyphema, other simultaneous findings (cataract, intravitreal hemorrhage, choroid rupture, sphincter tear, iridodialysis) stemming from the trauma are important for visual prognosis.[7-9] The aim of the present study was to investigate the demographic and clinical characteristics of grade 3 and 4 hyphema in pediatric patients.

MATERIALS AND METHODS Ethical approval was obtained from the Dicle University local ethics committee. Of the total number of 420 patients who were diagnosed as hyphema in Dicle University Department of Ophthalmology between January 2006 and December 2011, medical records of 136 pediatric patients were evaluated retrospectively.

The patients’ age, gender, affected eye, additional ocular pathologies, systemic diseases, and treatments were recorded.

The patients were classified according to the Agapitos et al.[11] classification. A total of 136 children with grade 3 (hyphema from ½ to near total in anterior chamber) or grade 4 (total hyphema) hyphema were enrolled in the study.

Patients with grades 1 and 2 hyphema, systemic diseases like diabetes mellitus, sickle cell anemia, kidney and/or liver diseases, penetrating eye trauma, use of anticoagulants, or age above 18 years were excluded.

358

At the time of admission, patients’ visual acuity (VA) based on Snellen’s chart, IOP measurements by Goldmann’s applanation tonometry and Tonopen (if applanation tonometry could not be applied to young children), and anterior segment and fundus examination findings were recorded. B-mode ocular ultrasonography was performed in patients who had total hyphema, traumatic cataract and/or vitreous hemorrhage.

All patients were hospitalized for treatment. As the standard therapy, all patients received topical prednisolone acetate 1% eye drops (Predforte, Allergan, Irvine, CA) 8 times daily and topical cyclopentolate hydrochloride 1% eye drop (Sikloplejin, Abdi İbrahim, Turkey) 2 times daily. They were followed up with bed rest, with the head of the bed elevated. Patients with IOP levels higher than 21 mmHg received timolol maleate (Timoptic, Merck, Sharpe & Dohme, West Point, PA) 2 times daily. For patients with uncontrolled IOP, dorzolamide + timolol maleate combination (Cosopt, Merck & Co, Inc., Whitehouse Station, NJ) 2 times daily and oral acetazolamide (Diazomid, Sanofi, Turkey) 2 times daily were added to the treatments.

In patients who had total anterior chamber hyphema, uncontrolled IOP, and corneal blood staining, hemorrhage was cleaned by anterior chamber lavage.

During follow-up examinations, presence of fresh blood elements in the anterior chamber was accepted as recurrence of hemorrhage. The last examinations were done after total clearance of the hyphema in uncomplicated cases or after the treatment of complications in complicated cases. During the last visit examination, VA, IOP, and anterior and posterior segment complications were recorded.

Statistical analyses were performed using the Statistical Package for the Social Sciences program (SPSS 15.0 Inc, Chicago, USA). To check for normal distribution, the Kolmogorov-Smirnov test was performed.

Student’s t-test and one-way ANOVA test were used to compare the parameters with normal distribution.

Mann-Whitney U and Kruskal-Wallis tests were used to compare nonparametric parameters. Categorical data were analyzed with the chi-square or the Fisher exact test.

RESULTS The mean ages of grade 3 and 4 patients were 10.1±3.8 and 9.3±4.0 years, respectively (range, 1-18 years, p>0.05). There was no significant difference between grade 3 and 4 patients in terms of the mean age.

The patients were mostly distributed in the age interval of 7-12 years (39.7%) (Fig. 1). The number of male subjects (80.1%) was significantly higher than of female (19.9%) subjects (4:1). Sixty-four (47.1%) patients had trauma to their right eye and 72 (52.9%) to their left eye. None of the patients had bilateral hyphema.

Temmuz - July 2013

Demographic and etiologic characteristics of children with traumatic serious hyphema

39.7

40.0%

40.0%

39.0

34.6

30.0% Percent

25.7

Percent

30.0%

20.0%

20.0%

18.4 13.2

10.0%

10.0%

0.0%

0.0%

12.5 8.1

6.6 2.2

0-6

7-12 Age

13-18

Stone

Bead Foreign Home Explosive Fall and (toy gun) body accident others

Ball

Etiology

Fig. 1. Distribution of the patients according to age.

Fig. 2. Distribution of the etiologic factors leading hyphema.

Etiologic factors for trauma were stone in 53 (39%), bead bullet (toy gun) in 25 (18.4%) and others in 58 (42.6%) patients (Fig. 2). There was no significant relationship between the etiologic factors and VA, IOP and recurrence of hyphema (p>0.05). When the patients were grouped according to intensity of the hyphema, 38.2% were grade 3 and 61.8% were grade 4.

The frequency of grade 4 hyphema was significantly lower in bead bullet (toy gun)-induced hyphema when compared to stone or other etiologic reasons (Fig. 3, p=0.046).

In the follow-up period, 114 (83.8%) patients responded to the medical treatment, whereas 22 cases underwent surgery due to complications. The most common surgical intervention was cataract surgery (4.4%) followed by trabeculectomy (4.4%) (Table 3).

Etiological factors were similar in grades 3 and 4 hyphema.

The mean initial VA of the patients was 0.13±0.22.

During the follow-up period, the mean VA increased to 0.81±0.32. Fifteen percent of the patients had a final VA less than 0.5 and 6% of the patients had a final VA less than 0.1. Both initial and final VA and IOP were found to be lower in grade 4 patients than in grade 3 patients (Table 4). The most common complication was traumatic mydriasis (19.1%), followed by cataract (9.6%) and glaucoma (5.1%) (Table 2). The complication profile was found to be similar between the grade 3 and 4 patients (p>0.05).

One hundred and twenty-three patients were followed up without any surgical intervention. One (1.9%) patient in the grade 3 group and 12 (9.6%) patients in the grade 4 group underwent surgery (p=0.017). Need for surgery was higher in grade 4 patients. At the initial admission, 11 (8.1%) patients needed anterior chamber lavage and 2 (1.5%) patients needed conjunctival exploration surgeries. There was no significant relationship between the etiology of trauma and need for surgery (p=0.751).

Cilt - Vol. 19 Sayı - No. 4

DISCUSSION The frequency of hyphema is 17-20/100.000 in the general population. In children, the most common finding following ocular trauma is hyphema, and it occurs in 32% of all traumas.[11,12] Hyphema develops mostly 50.0% 40.0%

Grade 4 3

46.4 41.7

36.5

34.6 28.8

30.0%

Percent

The most frequent accompanying symptoms to hyphema were corneal epithelial defect (49.3%) and rise in IOP higher than 21 mmHg (35%) during the first admission to the hospital (Table 1).

Recurrent bleeding occurred in 9 patients. However, there was no significant relationship between recurrent bleeding and hyphema grade or etiology of the trauma (p>0.05).

20.0% 11.9

10.0% 0.0%

Stone

Bead (toy gun)

Others

Etiology

Fig. 3. Distribution of the etiologic factors according to severity of hyphema.

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Table 1. Frequency of the accompanying findings of hyphema

Frequency (Percent)

n %

No additional finding Corneal epithelial defect Intraocular pressure increase Iridodialysis Cataract Vitreus hemorrhage Retinal hemorrhage Retinal detachment Macular edema Eyelid laceration

42 67 48 6 1 5 6 1 2 6

30.9 49.3 35.3 4.4 0.7 3.7 4.4 0.7 1.5 4.4

following a blunt ocular trauma, and two-thirds of the patients are male subjects.[13,14] Previous studies have included all age groups and all grades.[11,14,15] As our hospital is the largest health center of the region, we reached the records of 136 children with grades 3 and 4 hyphema. To the best of our knowledge, this is the first study that has evaluated traumatic serious hyphema in pediatric patients. In contrast to the previous studies, we aimed to determine accompanying ocular pathologies, complications, need for surgery, and surgical outcomes in pediatric patients with grades 3 and 4 hyphema.

Hyphema resulting from blunt eye trauma may be seen in all age groups, but it has been reported more commonly in children at 10-19 years of age.[16,17] In our study population, hyphema was most frequently seen (39.7%) among the children between 7-12 years of age. The etiologic factors for blunt trauma in our study population were similar to those of previous studies.[3,14,15,18] Grade 4 hyphema was less frequent in

Table 2. Frequency of complications seen in hyphema

Frequency (Percent)

n %

None Mydriasis Cataract Glaucoma Macular edema Vitreus hemorrhage Iridodialysis Nephelion Macular hole Choroidal rupture Retinal detachment

70 26 13 7 5 4 4 4 1 1 1

51.5 19.1 9.6 5.1 3.7 2.9 2.9 2.9 0.7 0.7 0.7

bead bullet (toy gun) injuries (40%) than in stone injuries (66%) and in “other” injuries (62%). This may be due to the smaller volume of bead bullets that may lead to milder injury.

Of the patients, 52.9% had trauma to their left eyes.

In a previous study, the left eye was reported to have greater exposure to trauma, and this was explained as being due to right hand preference, which may lead to reflex protection of the other eye.[15] Visual acuity usually decreases in patients with traumatic hyphema, especially more severally in grade 3 and 4 hyphemas.[14,19-22] In our series, vision loss was more severe in grade 4 than grade 3 patients.

The mean initial and final VA of grade 4 patients were found to be significantly lower than those of grade 3 patients. Lower initial VA in grade 4 hyphema patients is thought to be related to the level of blood inside the anterior chamber. However, for final VA, it is thought to be related with accompanying anterior and posterior

Table 3. Treatment distribution based on grading

Medical

Iridodialysis

Trab

PPV

2 2 4 (2.9)

1 5 6 (4.4)

0, 3 3 (2.2)

Grade 3 46 4 68 Total no. (%) 114 (83.8)

Ac lavage Cataract 1 2 3 (2.2)

2 4 6 (4.4)

PPV: Pars plana vitrectomy; Ac: Anterior chamber; Trab: Trabeculectomy.

Table 4. Visual acuity and intraocular pressure at admission and at the end of the follow-up period

Grade 3 Grade 4 p

Initial VA

Final VA

IOP (mmHg)

Final IOP

0.201±0.233 0.082±0.197 <0.0001

0.88±0.26 0.77±0.34 0.029

15.4±6.8 22.3±10.5 <0.0001

12.8±4.8 14.05±5.1 0.041

VA: Visual acuity; IOP: Intraocular pressure.

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Demographic and etiologic characteristics of children with traumatic serious hyphema

segment complications like traumatic cataract, glaucoma, iridodialysis vitreus hemorrhage, macular edema, and retinal detachment, as previously reported.[1,19-24] The results of the current study were similar to those of previous studies conducted on traumatic hyphemas in adults with respect to the frequency of complications.[1,4,14,18,22] Increase in IOP is common in traumatic hyphema patients, especially in grades 3 and 4. Read and Goldberg reported that IOP was higher than 25 mmHg in 25% of the traumatic hyphema patients at admission.

This is due to obstruction in the trabecular meshwork and increased incidence of pupillary block.[1,19,25] In our study population, 35% of the patients had an IOP higher than 21 mmHg. In addition, initial and final IOP levels were significantly higher in grade 4 patients compared to grade 3 patients. Anti-glaucomatous topical treatment was started in patients with a high IOP level. Eleven patients underwent anterior chamber lavage because of uncontrolled IOP. One patient with grade 3 and 5 patients with grade 4 underwent trabeculectomy because of uncontrolled IOP with anti-glaucomatous medication and anterior chamber lavage. Intractable glaucoma may develop because of angle recession in these patients, which was reported at a rate of 6-10% in various studies.

According to some reports, glaucoma may develop many years after the trauma. This may be explained by the long-term complications of mild iridocorneal angle injury.[1,25,26] Topical steroids, cycloplegic agents, antifibrinolytics, systemic steroids, and systemic aminocaproic acid may be used in the treatment of traumatic hyphema of children. These treatment options enable clearance of blood from the anterior chamber and prevent recurrent bleeding.[27,28] Hyphema was entirely resolved with topical steroids and cycloplegic agents in 83.8% (114) of our patients. Re-bleeding occurred in 9 patients (after medical treatment or surgical treatment), and 3 of them needed anterior chamber lavage. The rate of rebleeding in traumatic hyphema was reported as 4.1%35% in different patient series.[14,16,20,21] Re-bleeding usually occurs during clot retraction and fibrinolysis.

Some studies found a correlation between re-bleeding and the severity of the initial bleeding. It has also been reported that re-bleeding was associated with worse VA and higher complication rates.[1,22,27,29-31] In our study, grade of disease, VA and complication rates were similar in patients with and without re-bleeding.

The rate of re-bleeding was lower in our study. This may be due to hospitalization of all patients, immobilization by bed rest, topical steroid use, lack of sickle cell anemia, and being of Caucasian race.

In conclusion, visual prognosis was found to be negatively affected by the presence of additional ocuCilt - Vol. 19 Sayı - No. 4

lar pathologies in grade 3 and 4 traumatic hyphema patients. Grade 4 patients had lower initial and final VA, higher IOP levels and a higher surgery rate with respect to grade 3 patients. There were no significant correlations between the etiologic factors and VA, IOP, accompanying findings, complications, or surgery rates. Serious complications were seen in 49% of all patients. VA was less then 0.5 in 15% and less then 0.1 in 6% of the patients. Close follow-up and appropriate treatment in patients with serious hyphema may reduce complications and improve the negative course of the disease.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Walton W, Von Hagen S, Grigorian R, Zarbin M. Management of traumatic hyphema. Surv Ophthalmol 2002;47:297334.

2. Pearlman JA, Au Eong KG, Kuhn F, Pieramici DJ. Airbags and eye injuries: epidemiology, spectrum of injury, and analysis of risk factors. Surv Ophthalmol 2001;46:234-42.

3. Lai JC, Fekrat S, Barrón Y, Goldberg MF. Traumatic hyphema in children: risk factors for complications. Arch Ophthalmol 2001;119:64-70.

4. Strahlman E, Elman M, Daub E, Baker S. Causes of pediatric eye injuries. A population-based study. Arch Ophthalmol 1990;108:603-6.

5. Kargı SH, Demirbay P, Özdal P, Yarpuz IM, Caliskan B, Teke M ve ark. Künt göz travmalarının klinik değerlendirilmesi. T Oft Gaz 2002;32:863-8.

6. Wilson FM. Traumatic hyphema. Pathogenesis and management. Ophthalmology 1980;87:910-9.

7. Wong TY, Tielsch JM. A population-based study on the incidence of severe ocular trauma in Singapore. Am J Ophthalmol 1999;128:345-51.

8. Canavan YM, Archer DB. Anterior segment consequences of blunt ocular injury. Br J Ophthalmol 1982;66:549-55.

9. Shiuey Y, Lucarelli MJ. Traumatic hyphema: outcomes of outpatient management. Ophthalmology 1998;105:851-5.

10. Campbell DG. Ghost cell glaucoma following trauma. Ophthalmology 1981;88:1151-8.

11. Agapitos PJ, Noel LP, Clarke WN. Traumatic hyphema in children. Ophthalmology 1987;94:1238-41.

12. DeRespinis PA, Caputo AR, Fiore PM, Wagner RS. A survey of severe eye injuries in children. Am J Dis Child 1989;143:711-6.

13. Farber MD, Fiscella R, Goldberg MF. Aminocaproic acid versus prednisone for the treatment of traumatic hyphema. A randomized clinical trial. Ophthalmology 1991;98:279-86.

14. Spoor TC, Kwitko GM, O’Grady JM, Ramocki JM. Traumatic hyphema in an urban population. Am J Ophthalmol 1990;109:23-7.

15. Ashaye AO. Traumatic hyphaema: a report of 472 consecutive cases. BMC Ophthalmol 2008;8:24.

16. Ng CS, Strong NP, Sparrow JM, Rosenthal AR. Factors related to the incidence of secondary haemorrhage in 462 patients with traumatic hyphema. Eye (Lond) 1992;6:308-12.

17. Fong LP. Secondary hemorrhage in traumatic hyphema.

Predictive factors for selective prophylaxis. Ophthalmology 1994;101:1583-8.

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18. Baker RS, Wilson MR, Flowers CW Jr, Lee DA, Wheeler NC. Demographic factors in a population-based survey of hospitalized, work-related, ocular injury. Am J Ophthalmol 1996;122:213-9.

19. Rakusin W. Traumatic hyphema. Am J Ophthalmol 1972;74:284-92.

20. Kearns P. Traumatic hyphaema: a retrospective study of 314 cases. Br J Ophthalmol 1991;75:137-41.

21. Kennedy RH, Brubaker RF. Traumatic hyphema in a defined population. Am J Ophthalmol 1988;106:123-30.

22. Mela EK, Dvorak GJ, Mantzouranis GA, Giakoumis AP, Blatsios G, Andrikopoulos GK, et al. Ocular trauma in a Greek population: review of 899 cases resulting in hospitalization. Ophthalmic Epidemiol 2005;12:185-90.

23. Jan S, Khan S, Mohammad S. Hyphaema due to blunt trauma. J Coll Physicians Surg Pak 2003;13:398-401.

24. Macewen CJ. Eye injuries: a prospective survey of 5671 cases. Br J Ophthalmol 1989;73:888-94.

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25. Read J, Goldberg MF. Comparison of medical treatment for traumatic hyphema. Trans Am Acad Ophthalmol Otolaryngol 1974;78:799-815.

26. Kaufman JH, Tolpin DW. Glaucoma after traumatic angle recession. A ten-year prospective study. Am J Ophthalmol 1974;78:648-54.

27. Salvin JH. Systematic approach to pediatric ocular trauma.

Curr Opin Ophthalmol 2007;18:366-72.

28. Crouch ER Jr, Frenkel M. Aminocaproic acid in the treatment of traumatic hyphema. Am J Ophthalmol 1976;81:35560.

29. Edwards WC, Layden WE. Traumatic hyphema. A report of 184 consecutive cases. Am J Ophthalmol 1973;75:110-6.

30. Amoni SS. Traumatic hyphaema in Kaduna, Nigeria. Br J Ophthalmol 1981;65:439-44.

31. Abraham DI, Vitale SI, West SI, Isseme I. Epidemiology of eye injuries in rural Tanzania. Ophthalmic Epidemiol 1999;6:85-94.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):363-365

Case Report

Olgu Sunumu doi: 10.5505/tjtes.2013.89138

Künt travmanın nadir komplikasyonu; Çocuk olguda diyafram-perikart rüptürü ve kardiyak herniasyon A rare complication of blunt trauma; diaphragm-pericardium rupture and cardiac herniation in a child case Ersin ARSLAN, Ahmet Ferudun IŞIK, Maruf ŞANLI, Ahmet ULUŞAN, Levent ELBEYLİ

Diyafram ve perikart yaralanmaları künt travma sonrası nadir görülür, tedavisi cerrahidir. Künt travma sonrası gelişen diyafram ve perikart rüptürü nedeniyle ameliyat edilen dört yaşında erkek olgu; bu birlikteliğin nadir görülmesi, çocuklarda klinik ve radyolojik özelliklerin farklılıkları irdelenerek sunuldu.

Diaphragma and pericardium rupture is rarely seen after blunt trauma. It’s treatment is surgery. A 4-year-old male patient who was operated for diaphragm and pericardium rupture which developed after blunt trauma; rarity of this union, differences in the clinical and radiological features in children was examined.

Anahtar Sözcükler: Çocuklarda travma; diyafram ve perikart rüptürü; kardiyak herniasyon.

Key Words: Children trauma; diaphragm and pericardium rupture; cardiac herniation.

Travma günümüzün en önemli sağlık ve sosyal sorunlarından biri olmaya devam etmektedir. Diyafram ve perikart yaralanmalarına künt travma sonrası nadiren rastlanır.[1] Künt travma sonrası diyafram rüptürü %3,3 olarak bildirilirken,[2] perikart rüptürü 20,000 künt travmalı olgunun sadece 22’sinde görülmüştür.[3] Tıbbi yazında künt travma sonrası diyafram-perikart rüptürü ile kalp herniasyonu birlikteliğine erişkinlerde olgu sunumları şeklinde rastlanılmıştır.

OLGU SUNUMU Araç dışı trafik kazası sonucu torakoabdominal bölgede künt travma gelişen dört yaşında erkek olgu, travma sonrası ikinci saatte getirildiği acil serviste değerlendirildi. Fiziksel incelemede sağ torakoabdomi-

nal bölgede cilt laserasyonları ve abrazyonları izlendi.

Takipneik solunumu olan olgunun nabzı 190/dk, 5 lt/ dk oksijen ile satürasyon değeri %84 idi. Sol hemitoraksta solunum sesi yoktu. Karın incelemesi normal olarak değerlendirilen olguya nazogastrik (NG) sonda yerleştirilerek arka-ön (PA) akciğer grafisi, göğüs-karın bilgisayarlı tomografisi (BT) çekildi. PA akciğer grafide mediyastenin sağa kaydığı, diyaframın solda izlenmediği ve NG sondanın sol hemitoraksta olduğu görüldü (Şekil 1a). Göğüs BT’sinde karın organları sol hemitoraksta izlendi (Şekil 1b). Fiziksel inceleme ve radyolojik olarak karın organlarına ait perforasyon bulgusuna rastlanmadı. Olguya genel anestezi altında sol torakotomi yapıldı. Diyaframın sol posterolateralden santral tendonu da içerecek şekilde mediyale doğru ve perikardın frenik sinir seyrince yaklaşık 6 cm yırtıldığı görüldü. Kalp bu defektten toraks içine herniye olmuştu. Mide, transvers kolon ve karaciğerin sol lobu toraksta izlendi. 50 cc hemorajik mayi aspire edildi, organlarda perforasyon izlenmemesi üzerine

Gaziantep Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, Gaziantep.

Department of Thoracic Surgery, Gaziantep University Faculty of Medicine, Gaziantep, Turkey.

Künt travma sonrası gelişen diyafram-perikart rüptürü ve kalp herniasyonu nedeniyle ameliyat edilen dört yaşında erkek olgu; bu birlikteliğin nadir görülmesi, çocuklarda klinik ve radyolojik özelliklerin farklılıkları irdelenerek sunuldu.

İletişim (Correspondence): Dr. Maruf Şanlı. Gaziantep Üniversitesi Tıp Fakültesi Göğüs Cerrahisi Anabilim Dalı, Gaziantep, Turkey.

Tel: +90 - 342 - 360 60 60 e-posta (e-mail): sanli@gantep.edu.tr

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(a)

(b)

Şekil 1. (a) Olgunun arka-ön akciğer grafisi ve (b) göğüs BT’sinde sol hemitoraksta NG sonda ve mideye ait görünüm izleniyor.

batına yerleştirildi. Diyafram atravmatik 0 ipek dikiş (Neosilk, Setpa, Türkiye) ile tek tek frenik sinir korunarak, perikartdaki defekt ise atravmatik 3/0 poliglikolik asit dikişle (Neocryl, Setpa, Türkiye) ile onarıldı (Şekil 2a). Akciğer parankiminde özellikle alt lobda yer yer kontüzyon alanları olduğu izlendi. Parankimde hematom bulgusuna rastlanmadı. Olgu ameliyathanede ekstübe edilerek servise alındı. Ameliyat sonrası herhangi bir komplikasyon gelişmeyen olguda ikinci gün ağızdan beslenme başlandı. Drenleri beşinci gün çekilen olgu işlem sonrası altıncı gün taburcu edildi. Olgunun yapılan kontrollerinde ameliyat sonrası üçüncü ay yakınmasının olmadığı, PA akciğer grafisinin normal olduğu belirlendi (Şekil 2b).

TARTIŞMA Diyafram ve perikart hem penetran hem de künt travma sonucu yaralanabilmektedir. Künt travma sonrası diyafram yaralanma sıklığı %3,3’tür.[2] Majör künt travmalı 20,000 olgunun incelenmesinde 22 olguda perikart rüptürü geliştiği saptanmıştır.[3] Olgumuzda da olduğu gibi özellikle alt toraks ve üst karın yaralanmalarında diyafram yaralanmasının daha sık gelişebileceği bilinmektedir.[4] Diyafram yırtığı gelişen olgular semptomsuz olabileceği gibi karın organların herniasyonu geliştiğinde, solunum veya gastrointestinal kanalın mekanik tıkanıklık semptomları da ortaya çıkabilmektedir. To-

Diyafram

Perikart

(a)

(b)

Şekil 2. (a) Diyafragma ve perikardın dikildikten sonraki görünümü, (b) ameliyat sonrası üçüncü ay arkaön akciğer grafisi.

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Çocuk olguda diyafram-perikart rüptürü ve kardiyak herniasyon

raksta bağırsak hareketlerinin duyulması tanıyı kolaylaştırır. Olgumuzda ilk incelemede toraksta bağırsak sesleri duyulmadı fakat ardından NG sondasından verilen hava sol hemitoraksta işitildi. Çocukların anatomik ve fizyolojik farklılıkları nedeni ile diyafram yaralanması tanısı erişkinden daha zor konulmaktadır.[5] Solunum sıkıntısı, karın-göğüs ağrısından şoka kadar değişen bulgular olmasına rağmen yandaş yaralanmalar bu bulguları maskeleyebilir ve çocuklar yakınmalarını tam olarak tarif edemeyebilirler. Olgumuzda torakoabdominal künt travma vardı.

Solunum sıkıntısı ve taşikardi mevcut olan olgumuzda bu bulguların diyafram yaralanması sonucu herniye olan karın organlarının bası etkisiyle oluştuğu düşünüldü. Perikart yaralanması ameliyat sırasında tespit edildi ve onarıldı. Perikart defektlerinde emilebilir greftler kullanılabildiği için dikiş materyali emilebilir seçildi.

Radyolojik olarak PA akciğer grafisi, BT, ekokardiyografi, manyetik rezonans görüntüleme ve kontrastlı grafiler tanı için kullanılmaktadır.[6] Özellikle göğüs BT tanı için genellikle faydalı bilgiler verir.[7] Diyafram yırtığının radyolojik olarak diyafram yükselmesi, lokalize pnömotoraks, plevral sıvı, akut mide dilatasyonu ile karışabileceği unutulmamalıdır. Olgumuzda PA akciğer grafide sol diyafram sınırları izlenmedi ve NG sondanın sol hemitoraksta olduğu görüldü. Göğüs BT’sinde ise midenin sol hemitoraksta olduğu izlendi.

Künt travmaya bağlı gelişen diyafram yırtılması genellikle soldadır ve yapısı gereği santral tendon nadiren yaralanır. Herniye olan organlar solda, genellikle mide, dalak, kalın bağırsaklar, karaciğer, omentum ve ince bağırsaklardır. Sağ rüptürlerde sıklıkla karaciğer yaralanması da olaya eşlik eder. Olgumuzda diyaframdaki yırtık santral tendonu da içine almaktaydı ve mide, kolon, karaciğer sol lobu toraksta izlendi.

Perikart rüptürlerinde kalp herniasyonu gelişebilir.

Perikart rüptürü kalp defekten herniye olmadıkça veya hemoraji gelişmedikçe genellikle semptomsuzdur.[9] Perikart rüptürü sonucunda gelişen kardiyak herniasyon, vasküler yıkım ve ani ölüme neden olabileceği için cerrahi olarak tamir edilmelidir.[9] Olgumuzda perikart rüptürü ve kalp herniasyonu ameliyat sırasında saptandı. Karın organların yer kaplayıcı etkisi ile kalp herniasyonunun hayatı tehdit eden komplikasyonlara yol açmadığı düşünüldü.

[1,8]

Diyafram rüptürleri laparatomi, torakotomi veya

Cilt - Vol. 19 Sayı - No. 4

torakoabdominal kesi ile onarılabilmektedir.[4] Olgumuzda ameliyat öncesi değerlendirmede karın organlarına ait perforasyon bulgusuna rastlanmadı ve bu nedenle torakotomi ile tamir seçildi. Perikart rüptürünün tanısının konulması ve tamirinde bu kesi bize avantaj sağladı. Ameliyat sonrası komplikasyon gelişmeyen olgu altıncı gün taburcu edildi.

Diyafram ve perikart yaralanmalarında eşlik eden organ yaralanmaları nedeniyle mortalitenin yüksek olabileceği unutulmamalıdır. Tanı koymak zordur ve genellikle intraoperatif konulabilir.[7,9] Tanı konulmasında en önemli etken rüptürden şüphelenmektir.[4] Sonuç olarak, çocuklarda künt travma sonrası diyafram ve perikart rüptürleri kolayca gözden kaçabilmektedir. Travma sonrası bu rüptürlerin gelişebileceğinin akılda tutulması tanının en önemli aşamasını oluşturur. Tanı konulduğunda ölümcül komplikasyonlar gelişmeden cerrahi ile tamir yapılmalıdır.

Yazar(lar) ya da yazı ile ilgili bildirilen herhangi bir ilgi çakışması yoktur.

KAYNAKLAR 1. Kamiyoshihara M, Nagashima T, Ibe T, Takeyoshi I. Rupture of the diaphragm and pericardium with cardiac herniation after blunt chest trauma. Gen Thorac Cardiovasc Surg 2010;58:291-4.

2. Mihos P, Potaris K, Gakidis J, Paraskevopoulos J, Varvatsoulis P, Gougoutas B, et al. Traumatic rupture of the diaphragm: experience with 65 patients. Injury 2003;34:169-72.

3. Fulda G, Brathwaite CE, Rodriguez A, Turney SZ, Dunham CM, Cowley RA. Blunt traumatic rupture of the heart and pericardium: a ten-year experience (1979-1989). J Trauma 1991;31:167-73.

4. Sanli M, Işik AF, Tunçözgür B, Meteroğlu F, Elbeyli L. Diagnosis that should be remembered during evaluation of trauma patients: diaphragmatic rupture. Ulus Travma Acil Cerrahi Derg 2009;15:71-6.

5. Brandt ML, Luks FI, Spigland NA, DiLorenzo M, Laberge JM, Ouimet A. Diaphragmatic injury in children. J Trauma 1992;32:298-301.

6. Sharma OP. Pericardio-diaphragmatic rupture: five new cases and literature review. J Emerg Med 1999;17:963-8.

7. Farhataziz N, Landay MJ. Pericardial rupture after blunt chest trauma. J Thorac Imaging 2005;20:50-2.

8. Witkowski Z, Lasek J, Wujtewicz M, Stasiak M, Marks W, Kawecka A. Pericardiodiaphragmatic rupture and cardiac herniation after multiple blunt trauma: diagnostic and therapeutic difficulties. J Thorac Cardiovasc Surg 2005;130:1-2.

9. Khalpey Z, Rajab TK, Schmitto JD, Camp PC. Traumatic pericardial rupture with skeletonized phrenic nerve. J Cardiothorac Surg 2011;6:6.

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Ulus Travma Acil Cerrahi Derg 2013;19 (4):366-370

Case Report

Olgu Sunumu doi: 10.5505/tjtes.2013.29938

Traumatic renal artery occlusion in the pediatric age group: a case and review of the literature Pediatrik yaş grubunda travmatik renal arter oklüzyonu: Bir olgu ve literatürün gözden geçirilmesi Saurabh GARGE, Ravi KANOJİA, Kln RAO

Blunt trauma represents a major cause of death in children.

The incidence of renal arterial injuries in these cases is less than 1%. Traumatic renal artery occlusion is a rare occurrence in the pediatric age group. However, there is lack of information on the exact incidence and results of the management of these rare cases in the pediatric age group. We report herein a case and we review the available literature of this severe injury in the pediatric age group.

Künt travma çocuklarda başlıca ölüm nedenini oluşturmaktadır. Renal arter yaralanmalarının görülme sıklığı %1’den düşüktür. Pediyatrik yaş grubunda travmatik renal arter oklüzyonu nadiren oluşmaktadır. Ancak, çocuk yaştaki bu nadir olguların kesin insidans ve tedavi sonuçları hakkında bilgi eksikliği vardır. Bu yazıda bir olgu sunuldu ve pediyatrik yaş grubunda bu ağır travmaya ilişkin mevcut literatür gözden geçirildi.

Key Words: Traumatic renal artery occlusion; blunt trauma; children.

Anahtar Sözcükler: Travmatik renal arter oklüzyonu; künt travma; çocuk.

Traumatic renal artery occlusion in the pediatric age group is rare.[1-3] Children are more prone to these injuries owing to their anatomical vulnerability.[4] The various studies reported in the literature dealing with the management of renal arterial injuries have included both pediatric and adult cases. The management guidelines have been the same for adult and pediatric cases. We reviewed the literature regarding these rare injuries with a pediatric perspective.

modynamically stable. On inspection of her abdomen, there was bruising present on the left flank. On palpation, it was soft with mild tenderness in the right hypochondrium, with no guarding or rigidity. Abdominal radiograph was normal. Ultrasound of the abdomen showed grade 3 left renal injury with associated grade 3 splenic injury. A contrast-enhanced computerized tomography (CT) scan performed in the hospital where she received primary treatment (4 hours after injury) showed non-enhancement of the left kidney with associated surrounding hematoma. A grade 3 splenic injury and peripheral rim sign were also present. No contrast was seen delineating the left ureter (Fig. 1).

The right kidney was normal.

CASE REPORT A four-year-old female presented to the emergency room with alleged history of accidental fall from a bike. She had been struck by a pole and presented as a case of blunt trauma to the abdomen. The patient was referred to us 48 hours after injury, during which time she was resuscitated in a peripheral hospital, where she was transfused two aliquots of blood and kept nil per os, on fluids. Clinically, the child was he-

Department of Pediatric Surgery, PGIMER, Chandigarh, India.

She was catheterized but had no hematuria, and urea/creatinine levels were also normal. Urine output over 24 hours was adequate. However, routine urine microscopy showed presence of 7 red blood cells (RBCs)/high power field (hpf) and was suggestive

PGIMER, Chandigarh, Çocuk Cerrahisi Anabilim Dalı, Hindistan.

Correspondence (İletişim): Saurabh Garge, M.D. PGIMER Chandigarh, Department of Pediatric Surgery, Chandigarh, India.

Tel: +0091 - 9878691012 e-mail (e-posta): saurabhgarge8@gmail.com

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Traumatic renal artery occlusion in the pediatric age group

Fig. 1. CT scan showing non-enhancement of the left kidney.

of microscopic hematuria. Suspecting a diagnosis of renal artery occlusion and anticipating intervention, urgent intravenous urography (IVU), dimercaptosuccinic acid (DMSA) scan and CT angiography were done. IVU and DMSA showed the left kidney to be non-functional (Fig. 2). Ultrasound Doppler showed the left renal artery could be visualized to about 2 cm from its origin; however, distally for a length of 2 cm it was attenuated. Distally, few polar vessels were still seen. A CT angiography was done (50 hours after injury), which showed left renal artery occlusion for a length of approximately 1.1 cm. The spleen showed presence of a 2x2.4 cm intracapsular hematoma in the lower pole and pancreas, and other viscera were reported to be normal (Fig. 3).

Owing to the cost constraints, unilateral injury and delayed diagnosis, the child was managed conservatively. After a follow-up of one year, the child remains normotensive and had no febrile urinary tract infections. A repeat color Doppler showed maintained vascularity only in the upper pole of the left kidney.

The follow-up DMSA scan showed cortical function only in the upper pole with a differential renal function of 8%. The patient remains on regular follow-up for development of urinary tract infections and hypertension.

DISCUSSION In children, trauma represents the single commonest cause of death, and injury to the kidney from blunt or penetrating trauma is the most common urinary tract injury. Traumatic renal artery occlusion in the pediatric age group is rare. Various large studies reCilt - Vol. 19 Say覺 - No. 4

port the overall incidence of renal artery injuries as 0.05%,[1] 0.08%[2] and 0.1%.[3] However, specific data on the incidence on the basis of age are lacking.

Traumatic renal artery occlusion is more common in the left and in individuals under 25 years of age, and bilateral involvement is extremely rare.[1] Children are more likely than adults to sustain major renal injury with lesser severity of trauma. The presence of decreased perirenal fat, weaker abdominal muscles and a less well-ossified thoracic cage offer less protection to the kidney. In addition, the larger size of pediatric kidneys in relation to the rest of the body, retention of fetal lobulations and presence of congenital anomalies may permit easier parenchymal disruption.[4] A review of the literature showed very few pediatric patients with traumatic renal artery injury. Haas et al.,[5] in their series of 12 cases, had three pediatric patients. In another large series, by Elliott et al.,[6] no patient in the pediatric age group sustained main renal artery injury. Many other large series in the reviewed literature gave a mean age of presentation with no segregation of pediatric cases.[1] Thus, there is a paucity of literature in pediatric traumatic renal artery occlusion. Gonzalez et al. reported nine conservatively managed pediatric cases. There are also three pediatric cases reported that were managed by endovascular treatment.[7-10] The described mechanisms of injury that result in traumatic renal injury are acceleration/ deceleration injury of the comparatively fixed renal vascular pedicle, compression of the renal artery against the vertebral bodies of the spine, giving rise to intimal damage 367

Ulus Travma Acil Cerrahi Derg

Fig. 2. Intravenous urography showing no contrast excretion by the left kidney.

of the vessel and thrombosis, and sometimes injury by fractured rib segments.[5] Traumatic renal arterial thrombosis almost never occurs as an isolated event and indicates major associated injuries.[3] The information on the physical examination is insufficient to establish a diagnosis. Flank bruising, proteinuria or hematuria may be observed, but are often nonspecific.

[1-3,7] Our patient had flank bruising but no gross hematuria. However, microscopic hematuria was found later.

Contrast-enhanced CT scanning is the modality of choice for diagnosis and follow-up after treatment of blunt traumatic renal artery occlusion.[3,11] Findings of 368

the CT scan suggestive of renal arterial thrombosis include an absence of both renal parenchymal enhancement and contrast excretion in the affected kidney.

Also, a thin rim of contrast enhancement, often described as the rim sign, may be noted.[11] Angiography is equally useful for predicting the blockade, and is the investigation of choice if segmental obstruction to the blood flow is present. However, angiography will not be helpful to rule out and delineate the extent of associated injuries like retroperitoneal hematoma. Instead, helical CT provides the diagnosis and predicts the level of blockade as well, in case revascularization is to be planned.[12] In our case, we had ordered a contrast-enhanced CT with a CT angiography after 50 Temmuz - July 2013

Traumatic renal artery occlusion in the pediatric age group

Fig. 3. CT scan showing left renal artery thrombosis.

hours of injury, anticipating intervention. In a center in which CT angiography is available, modalities like IVU and DMSA scans do not provide any additional information that can modify the intervention strategies in any way. However, it is important to document the non- functionality of the renal unit under consideration by various methods in order to avoid unnecessary litigations in medicolegal cases. The documentation becomes more important in cases here in India where the late referral is a very common reason for delay in appropriate intervention.

Anecdotal case reports suggest that severe time constraints influence successful revascularization of the occluded renal artery. Classically, it is thought that the kidney tolerates warm ischemia for only 1 hour.[2,3] Successful revascularization has been reported within 24 hours and even 7 days post-injury, suggesting that, under rare and poorly understood circumstances, the kidney withstands longer periods of ischemia than generally believed. This occasional survival might be a result of incomplete occlusion of the renal artery or flow from collateral circulation.[10] The optimal treatment for this entity is not well established and has been controversial. The rarity of the condition, delayed diagnosis, presence of other asCilt - Vol. 19 Say覺 - No. 4

sociated life-threatening injuries or condition, and the disappointing long-term results of revascularization procedures are usually responsible for the lack of optimal treatment. Furthermore, in the Indian scenario, these patients are usually managed conservatively at set-up-lacking facilities and are later referred to higher centers for further management. This leads to loss of precious time, which plays a pivotal role in renal injuries and salvage of the jeopardized kidney. Our review of the literature has shown a definite change in trend from nephrectomies to preservation by revascularizations. With advances in radiology and resuscitative measures, the open revascularization procedures are preferably done by percutaneous means (mainly because of minimal invasiveness) in cases of both unilateral and bilateral traumatic renal artery occlusion, although the evidence for this sort of management comes mainly from case reports.

Treatment options include immediate surgical revascularization, nephrectomy and non-operative conservative therapy.[1-3] Jawas et al.[3] advocated conservative treatment in unilateral cases, with surgical revascularization required only in cases of bilateral injuries and injuries associated with solitary kidneys. The same is applicable to pediatric patients. Haas et al.[5] in 369

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their series of 12 cases had three pediatric patients. In all three, revascularization was attempted, but resulted in nephrectomies in two and a differential function of <10% in one who later developed hypertension.

Only three pediatric cases have been reported to have undergone endovascular treatment for renal arterial injuries. Halachmi et al.[8] and Vidal et al.[10] reported endovascular treatment in a renal artery pseudoaneurysm and Hsu et al.[9] reported it in a renal artery pseudo-occlusion by an intimal flap. The procedure was successful in the cases with pseudoaneurysms, while in the latter, it was associated with shunt stenosis and nephrectomy.

The follow-up of these conservatively managed patients is very important, and includes scintigraphy scans to delineate the function in the conservatively managed kidneys. Another important issue is development of hypertension in these conservatively managed cases. About 25-50% of the patients will develop hypertension; most patients who develop renovascular hypertension do so within the fist year, with a mean of 96 days.[5] These patients may need delayed nephrectomy. However, the incidence of hypertension is less in pediatric cases of renal artery occlusion. In a retrospective study, Cortes-Gonzalez et al.[7] reported hypertension to be present in only 2 of 9 pediatric cases reported. The reason for this may be age and absence of age- related vascular disorders already present before the time of trauma. The paucity of age-based literature makes it difficult to optimally answer this issue and raises a need for studies in larger series. However, close regular follow-up is required to assess the effect of conservative management on blood pressure.

In conclusion, traumatic renal artery occlusion in the pediatric age group is rare and under reported. The lack of age-based comparisons in larger series has led to the application of the same treatment algorithm as that used in adults. An age-related comparison among various factors with respect to the time of intervention, results of various procedures, and follow-up in the form of incidence of hypertension may provide

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some clues to the different management of this rare occurrence in pediatric age groups.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Sangthong B, Demetriades D, Martin M, Salim A, Brown C, Inaba K, et al. Management and hospital outcomes of blunt renal artery injuries: analysis of 517 patients from the National Trauma Data Bank. J Am Coll Surg 2006;203:612-7.

2. Bruce LM, Croce MA, Santaniello JM, Miller PR, Lyden SP, Fabian TC. Blunt renal artery injury: incidence, diagnosis, and management. Am Surg 2001;67:550-6.

3. Jawas A, Abu-Zidan FM. Management algorithm for complete blunt renal artery occlusion in multiple trauma patients: case series. Int J Surg2008;6:317-22.

4. Brown SL, Elder JS, Spirnak JP. Are pediatric patients more susceptible to major renal injury from blunt trauma? A comparative study. J Urol 1998;160:138-40.

5. Haas CA, Dinchman KH, Nasrallah PF, Spirnak JP. Traumatic renal artery occlusion: a 15-year review. J Trauma 1998;45:557-61.

6. Elliott SP, Olweny EO, McAninch JW. Renal arterial injuries: a single center analysis of management strategies and outcomes. J Urol 2007;178:2451-5.

7. Cortés-González JR, Arratia-Maqueo JA, Garza-Cortés R, Gómez-Guerra LS. Is age a predictor for the development of hypertension in conservatively managed unilateral renal artery occlusion secondary to blunt abdominal trauma?. [Article in Spanish] Actas Urol Esp 2010;34:634-7. [Abstract] 8. Halachmi S, Chait P, Hodapp J, Bgli DG, McLorie GA, Khoury AE, et al. Renal pseudoaneurysm after blunt renal trauma in a pediatric patient: management by angiographic embolization. Urology 2003;61:224.

9. Hsu W, Mitchell SE, Kim HS. Renal artery stenting for intimal flap injury in a 2-year-old child after blunt abdominal trauma. South Med J 2006;99:884-7.

10. Vidal E, Marrone G, Gasparini D, Pecile P. Radiological treatment of renal artery occlusion after blunt abdominal trauma in a pediatric patient: is it never too late? Urology 2011;77:1220-2.

11. Kawashima A, Sandler CM, Ernst RD, Tamm EP, Goldman SM, Fishman EK. CT evaluation of renovascular disease.

Radiographics 2000;20:1321-40.

12. Nuñez D Jr, Becerra JL, Fuentes D, Pagson S. Traumatic occlusion of the renal artery: helical CT diagnosis. AJR Am J Roentgenol 1996;167:777-80.

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Ulus Travma Acil Cerrahi Derg 2013;19 (4):371-374

Case Report

Olgu Sunumu doi: 10.5505/tjtes.2013.89656

Gebe bir kadında av tüfeği yaralanması sonucu fetüs beyin dokusunda rezidüel saçma tanesi: Bir olgu sunumu Residual pellet in fetal brain tissue following a gunshot injury to a pregnant woman: a case report Ümit Naci GÜNDOĞMUŞ,1 Harun AKKAYA,1 Kenan KARBEYAZ,2 Ayşe KESKİN1

Gebe bir kadına karşı işlenen yaralama suçlarında, hem annenin hem de fetüsün yaşamsal fonksiyonları ve oluşan zararların yaşam kalitesine etkisi neden sonuç ilişkisi açısından önem taşımaktadır. Ceza ve tazminat hukukunda ayrı ayrı değerlendirme zorunluluğu olan bu tür durumlarda annede doğurganlığı etkileyecek kalıcı organ kayıpları, fetüste ise vaktinden önce doğma ve kalıcı fonksiyonel bozuklukların niteliği ceza ve tazminat miktarında artırıcı etken olabilmektedir. Literatürde, ateşli silah yaralanmasına bağlı fetüste morfolojik ve fizyolojik değişimlerin ele alındığı ender sayıda olgu bildirimi bulunmaktadır. Bu yazıda, 41 yaşında, 27 haftalık gebe bir kadında ateşli silah yaralanması sonucu fetüs açısından oluşan durumun irdelenmesi amaçlandı. Anne normal sağlıklı bir yaşam sürdürür iken, dört yıllık gelişim evresinde çocuk yönünden belirgin şikayet hiperaktivite yakınması olmuştur. İntrauterin frontal lobu etkileyen bu lezyonun, çocukta ortaya çıkan ruhsal bulgulara etkisinin değerlendirilmesi önem taşımaktadır.

Vital functions and the effect of injuries on quality of life are important from a viewpoint of causation in willful injury crimes committed against a pregnant woman. In such conditions, which should be evaluated separately in criminal law and compensation law, permanent losses of organ function that may negatively affect the woman’s fertility, the features of permanent functional impairments and premature birth of the fetus can be additive factors for the indemnification amount. In scientific literature, case reports addressing the morphological and physiological changes to the fetus due to firearm injury are rare. In the presented case, we aimed to evaluate the fetus’s situation, following firearm injury to a 41-year-old woman at 27 weeks gestation. While the mother was living a healthy life, the significant problem of the child in the first four-year period of his development was hyperactivity. Evaluating the effect of the frontal lobe lesion on the psychiatric findings of the child is important.

Anahtar Sözcükler: Ateşli silah lezyonu; fetüs; gebelik; intrauterin yaralanma,

Key Words: Firearm injury lesion; fetus; pregnancy; intrauterine injury.

Gebe bir kadına karşı işlenen yaralama suçları, Türk hukuk sisteminde vücut dokunulmazlığına karşı işlenen suçlar başlığı altında ele alınmakta, suçun nitelikli (cezai yaptırımı ağırlaştıran) hali olarak adlandırılan gebe bir kadına yönelik olup çocuğun vaktinden önce doğmasına neden olma, çocuk yapma yeteneğinin kaybı, organlarından birinin işlevinin sürekli zayıflaması ya da yitirilmesi, iyileşmesi olanağı bulunmayan bir hastalığa neden olma başlıkları

altında durum saptamalarının yapılması istenmektedir.

Ayrıca uygulanan travma ile oluştuğu iddia edilen zararlar arasında neden sonuç ilişkisi de hukuki açıdan büyük önem taşımaktadır. Bu tür olgulara müdahale eden veya daha sonra tedavi ve takibini üstlenen değişik branş hekimlerinin klinik ve travmatik bulguların varlığını ve niteliklerini ayrıntılı olarak tanımlamada gösterdikleri özen, günümüz hukukunda adalet ilkesinin gerçekleşmesindeki en önemli belirleyicidir.

1 Adli Tıp Kurumu Başkanlığı, İstanbul; Adli Tıp Kurumu Eskişehir Şube Müdürlüğü, Eskişehir.

2

1 Council of Forensic Medicine, Istanbul; Council of Forensic Medicine, Eskisehir Branch Manager, Eskisehir, Turkey.

2

İletişim (Correspondence): Dr. Kenan Karbeyaz. Eskişehir Adli Tıp Şube Müdürlüğü, Eskişehir Adalet Sarayı, 26480 Eskişehir, Turkey.

Tel: +90 - 222 - 240 71 20 e-posta (e-mail): drkenankarbeyaz@hotmail.com

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Bu yazıda, 41 yaşında, 27 haftalık gebe bir kadında ateşli silah yaralanması sonucu fetüs beyin dokusunda rezidüel saçma tanesi kalan bir olguda, yaralanmanın adli tıbbi yönünün tartışılması ve doğum sonrası çocuk üzerindeki etkilerinin irdelenmesi amaçlandı.

OLGU SUNUMU Kırk bir yaşında, 27 haftalık gebe olan kadına, aynı aileden başka kişilerin de bulunduğu bir ortamda eniştesi tarafından 12 kalibrelik bir av tüfeği ile 1015 metreden ateş edildiği iddia edilmiştir. Ailenin 19 yaşındaki büyük oğlu, aldığı ateşli silah yaralanması sonucu ölmüştür. Düzenlenen tıbbi belgelerde gebe kadının yapılan fiziksel incelemesinde; boyunda, toraksta ve karında dörder adet av tüfeği saçma tanesi giriş deliği, alt ve üst ekstremitelerde de çok sayıda saçma tanesi giriş deliklerinin olduğu kaydedilmiştir.

Kişinin genel cerrahi uzmanı tarafından genel anestezi uygulanarak acil ameliyata alındığı, karında 700-800 cc kan görüldüğü, jejenumun mezenterik ve antimezenterik kenarlarında tespit edilen perforasyonların primer onarıldığı, uterus fundusunda da bir adet saçma tanesi giriş deliği görülüp dikildiği, diğer karın oluşumlarının normal bulunduğu, ameliyata kadın hastalıkları ve doğum uzmanının da katılımı sağlanarak anne ve fetüs yönünden gebeliğin sonlandırılmasına gerek görülmediği, tüm kontroller yapılarak ameliyata son verildiği belirtilmiştir. Ameliyat sonrası yapılan konsültasyonlarda çocuk kalp seslerinin alındığı ve intrauterin aktif kanama tespit edilmediği kayıt alına alınarak gebelik normal seyrine bırakılmıştır. Olay tarihinden yaklaşık 2.5 ay sonra sezaryen kesiyle gebelik sonlandırılmış, bebeğin fiziksel incelemesi normal olarak değerlendirilmiş, olay tarihinden 15 ay sonra çekilen beyin tomografisinde sisterna magnanın geniş olarak izlendiği, frontobazalde orta hatta yoğun metalik artefakta yol açan hiperdens oluşum (av tüfeği saçma tanesi) izlendiği bildirilmiştir. Çocuğun iki yaşında yapılan muayenesinde konuşma güçlüğü çektiği, sfinkter kontrolü olmadığı, AGTE testinde ince motor alanında geri bulunduğu, bilişsel gelişim, sosyal beceri ve özbakımın anlamlı derecede geri olduğu, kaba motor alanında normal olup yapılan testler sonucu hafif derecede zihinsel gelişim geriliği saptandığı, bu haliyle özür durumuna göre tüm vücut fonksiyon kaybı oranının %50 olarak saptandığı Sağlık Kurulu Raporu ile belgelendirilmiştir. Çocuğun en son yapılan kontrollerinde rezidüel saçma tanesinin oluşturabileceği zararlar açısından kanda kurşun düzeyi değerlendirilmiş ve 3.40 µg/dL (ref: 0.00-10.00 µg/dL) olarak tespit edilmiştir. Dava konusu olay nedeniyle Adli Tıp Kurumu 2. İhtisas Kurulu’na kontrole gönderilen dört yaşındaki çocuğun yapılan nörolojik incelemesinde belirgin bir patolojik bulgu gözlenmemiştir. Ancak annesinden alınan anamnezde çocuğun devamlı sinirli, uygunsuz hareketlerde bulunduğu iddia edilmiştir. Ailenin ya372

Şekil 1. Çocuğun 1,5 yaşında iken çekilmiş anterior-posterior ve lateral direkt kafa grafisinde saçma tanesi.

nında getirmiş olduğu, 1,5 yaşında çekilmiş ön-arka ve yan kafa grafisinde; frontobazal orta hatta saçma tanesi ile uyumlu metalik imaj izlenmiştir (Şekil 1).

TARTIŞMA Ateşli silah yaralanmaları, tüm dünyada olduğu gibi ülkemizde de mortalite ve morbitideyi azınsanmayacak ölçüde etkilemeye devam etmektedir.[1-4] Tüm yasal yaptırımlara karşın sosyokültürel olarak ateşli silah bulundurma ve kullanma alışkanlığı gerek kasti, gerek kaza orijinli ölüm ya da yaralanmalarla sonuçlanan zararları da beraberinde getirmektedir. Yasa koyucu, olgumuzda da olduğu gibi, kriminal bir olayda silah kullanılmasını ceza yönünden ağırlaştırıcı unsurlardan biri olarak belirtmiş, üstsoy ve altsoydan birine karşı gerçekleştirilmesi, oluşan yara sayısı, her bir yaranın oluşturduğu hasarın niteliği ve iyileşme olanağı bulunmayan sağlık sorunlarına neden olması gibi durumları suçun nitelikli hali olarak belirtmiş, bu durumların dava konusu olay ile bağlantısının (illiyet bağınınneden sonuç ilişkisinin) kurulması durumunda cezai yaptırımın katlanarak artması hükmü getirilmiştir. Bu Temmuz - July 2013

Gebe bir kadında av tüfeği yaralanması sonucu fetüs beyin dokusunda rezidüel saçma tanesi

amaçla tıbbi bilirkişi görüşü oluşturma sürecinin olay tarihinde hastanın ilk gözleminden başlayarak, olgumuzda olduğu gibi çocukluk çağı sürecinin uzun bir irdelemesini de içerebileceği göz ardı edilmemelidir.

Olgumuz, intrauterin dönemde frontal lobu ilgilendiren ve herhangi bir tıbbi girişim yapılmadan yaklaşık 2,5 ay normal fetal gelişimin devam ettiği av tüfeği saçma tanesi yaralanması olgusudur. Ateşli silah yaralanmaları yönünden kapsamlı çalışmalar yapılmış olmasına rağmen gebe kadınları baz alan, fetüsün durumunun da değerlendirildiği çalışmalara nispeten daha az rastlanmıştır. Wilson ve Swartz’ın[4] savaş zamanı ateşli silahlar ile yaralanan altı gebe kadını inceledikleri, iki fetüsün yaşatılabildiğini bildirdikleri araştırma ile Lin ve Gill’ın[5] 13 gebe kadının ateşli silah sonucu yaralandıkları ve yine iki fetüsün yaşatılabildiği, diğer gebeliklerin ölümle sonuçlandığı çalışmalar literatürde seri çalışma şeklinde yerini almış, araştırmacılar ender görülen bu durumlar karşısında olgu sunumları ile konunun önemini dile getirmişlerdir.

Gun ve arkadaşları,[6] bir olguda saçma tanelerinin fetüsün idrar kesesine penetre olduğu, 32 haftalık gebeliğin sonlandırılarak mesane onarımı yapıldığı ve bebeğin normal yaşamını sürdürebildiğini bildirilmişlerdir. Diğer bir ateşli silah yaralanması olgusunda da uterusun rüptüre olmasına rağmen fetüste yüzeyel cilt sıyrıkları saptandığı, hem anne hem de bebeğin yaşatılabildiği belirtilmiştir.[7] Bunlar dışında travmatik anhidroamnios ile uterusun lasere olduğu, ancak fetüsün yara almadığı, tıbbi girişimle gebeliğin sonlandırılıp anne ve çocuğun yaşatılabildiği olgular da bildirilmiştir.[8] Başka bir sunumda da plasentaya penetre saçma taneleri nedeniyle gebeliğin sonlandırıldığı bir olguya yer verilmiştir.[9] Muzumdar ve arkadaşlarının[10] yayınladıkları bir olguda, term döneminde gebe bir annenin havalı tüfekle intravajinal yolla kendisini yaraladığı bildirilmiştir. Kullanılan silah ve yaralanmanın orjini bizim olgumuza benzemese de, bu olguda sunulan fetüste sağ lateral ventrikülde saçma tanesi bulunduğu ve çocuğun altı yaşında mental sorunlarla yaşamını sürdürdüğü belirtilmektedir. Yapılan araştırmalarda, ateşli silah yaralanmasına bağlı vücutta kalan mermi çekirdeği ya da saçma tanesi artıklarının kan kurşun düzeyini artırdıkları ve buna bağlı uzun dönemli etkisi yanı sıra kısa dönemde kronik karın ağrısı, kusma ve anoreksiye neden olabileceği bildirilmiştir.

[11-13] Olgumuzda, akut dönemde görüldüğü bildirilen semptomların gelişmediği, kan kurşun düzeyinin 3.40 µg/dL olduğu tespit edilmiştir.

Dünya Sağlık Örgütü Ruhsal ve Davranışsal Bozuklukların 10. Gözden Geçirilmiş Uluslararası Sınıflandırılması tanı ölçütlerine göre “frontal lob sendromu” (FLS), genel tıbbi duruma bağlı kişilik değişimi, olarak adlandırılan ve klinikte travma ya da beyin hastalığına bağlı olarak kişilik ve davranış değişikCilt - Vol. 19 Sayı - No. 4

likleri ve bozuklukları şeklinde görülen tablo olarak nitelendirilmiştir. Etyolojisinde kafa travmaları önemli bir yer tutmaktadır. Hiperaktivite etyolojisinde ise genetik, nörobiyolojik, çevresel faktörler ile frontal lob disinhibisyonu etyolojik faktörler arasında gösterilmiştir.[14] Olgumuzun yaşının küçüklüğü, beyin dokusundaki saçma tanesinin konumu ve hiperaktivite başta olmak üzere mental uygunsuz davranışlar tanımlanması bir arada düşünüldüğünde frontal lob sendromu yönünden süreç içinde ilgili branş uzmanlarınca takibinin yapılması ve tanı testlerinin sürece yayılması gerektiği görüşü benimsenmiştir.

Gebelik travmalarında istenmeyen sonuçların önlenmesinde multidisipliner ekip çalışmasının önemi büyüktür. Ancak, teknik ve fiziki altyapı koşullarının ideale yakın olarak sağlandığı ortamlarda, multidisipliner ekip çalışmasının gerçek anlamda yararlarından söz edilebileceği de tüm çevrelerce kabul edilmektedir. Olumlu sonuçlar, anne ve fetüs sağlığının yeniden kazanımı yanı sıra hukuksal prosedürlerin sağlıklı ve tatmin edici biçimde sürdürülmesini de kapsamaktadır. Özellikle tıbbi bulguların tüm ayrıntılarıyla kronolojik sıra gözetilerek kayıt altına alınıp belgelenmesi, tüm tıbbi belge ve elde edilen delillerin evrensel etik ilkeler doğrultusunda korunarak adli mercilere sunulması yüksek özen gösterilmesi gereken unsurlar olarak karşımıza çıkmaktadır. Gösterilecek özen, hem mağdurların sağlığının yeniden kazanılmasında, sanık pozisyonunda suçlanan kişilerin hukuksal süreçteki durumunun belirlenmesinde, hem de hekim ve diğer sağlık personeli hakkında ortaya çıkma potansiyeli bulunan olumsuz durumların önlemesinde belirleyici olacaktır.

Yazar(lar) ya da yazı ile ilgili bildirilen herhangi bir ilgi çakışması yoktur.

KAYNAKLAR 1. Çetin G, Yorulmaz C. Ateşli silah yaraları. İçinde: Soysal Z, Çakalır C, editör. Adli Tıp, İstanbul: İstanbul Üniversitesi Basımevi ve Film Merkezi; 1999. 2. cilt. s. 519, 561-87.

2. Yıldırgan Mİ, Akçay MN, Çapan MY, Çelebi F, Çelik S, Atamanalp SS ve ark. Karın içi organların ateşli silah yaralanmaları. Ulusal Travma Dergisi 1996;2:169-72.

3. Celen O, Oğuz S, Doğan M. Abdominal gunshot wounds: retrospective analysis of 164 patients. Ulus Travma Derg 2001;7:258-61.

4. Wilson F, Swartz DP. Gunshot and war projectile wounds of the gravid uterus. Case report and review of literature. J Natl Med Assoc 1972;64:8-13.

5. Lin P, Gill JR. Homicides of pregnant women. Am J Forensic Med Pathol 2011;32:161-3.

6. Gun F, Erginel B, Günendi T, Celik A. Gunshot wound of the fetus. Pediatr Surg Int 2011;27:1367-9.

7. Carugno JA, Rodriguez A, Brito J, Cabrera C. Gunshot wound to the gravid uterus with non-lethal fetal injury. J Emerg Med 2008;35:43-5.

8. Ward HR, van Deurzen DF, van Dongen PW. Gunshot uterine rupture: a case report. Eur J Obstet Gynecol Reprod Biol 373

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1998;80:279-81.

9. Overstreet K, Mannino FL, Benirschke K. The role of placental pathology in the evaluation of interpersonal violence: a case of abdominal gunshot wound in a 27-week gravid uterus. J Perinatol 2002;22:675-8.

10. Muzumdar D, Higgins MJ, Ventureyra EC. Intrauterine penetrating direct fetal head trauma following gunshot injury: a case report and review of the literature. Childs Nerv Syst 2006;22:398-402.

11. John BE, Boatright D. Lead toxicity from gunshot wound.

374

South Med J 1999;92:223-4.

12. Kikano GE, Stange KC. Lead poisoning in a child after a gunshot injury. J Fam Pract 1992;34:498-500, 502, 504.

13. Coon T, Miller M, Shirazi F, Sullivan J. Lead toxicity in a 14-year-old female with retained bullet fragments. Pediatrics 2006;117:227-30.

14. Öncü B, Şenol S. Dikkat eksikliği hiperaktivite bozukluğunun etiyolojisi. Bütüncül Yaklaşım Klinik Psikiyatri 2002;5:1119.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):375-379

Case Report

Olgu Sunumu doi: 10.5505/tjtes.2013.97254

Bouveret syndrome: evaluation with multidetector computed tomography and contrast-enhanced magnetic resonance cholangiopancreatography Bouveret sendromu: Çok kesitli bilgisayarlı tomografi ve kontrastlı manyetik rezonans kolanjiyografi bulguları Oktay ALGIN,1 Evrim ÖZMEN,1 Melike Ruşen METİN,1 Pamir Eren ERSOY,2 Mustafa KARAOĞLANOĞLU1

Cholecystenteric fistula is one of the rarest complications of biliary lithiasis, with a frequency of less than 1%. Bouveret syndrome is a gastric outlet obstruction produced by gallstone(s) located in the distal stomach or proximal duodenum. The route of gallstone migration to the bowel is most commonly via a cholecystoduodenal fistula; however, fistulization of the stomach is a rarer variation. Early diagnosis of this situation is crucial to reduce morbidity and mortality. In this report, we present a patient with cholecystogastric fistula and Bouveret syndrome. To our knowledge, there is no published paper in the literature related to the diagnosis of Bouveret syndrome with multidetector computed tomography (MDCT) (64 detectors) and/or contrast-enhanced magnetic resonance cholangiopancreatography (CE-MRCP). Our aim was to discuss the efficacy of MDCT and CE-MRCP in the detection and evaluation of cholecystenteric fistulas. We showed the exact localization and relation of biliary stones and the fistula by MDCT and CE-MRCP. We also evaluated the biliary system with CE-MRCP physiologically. In conclusion, when biliary lithiasis and ileus are detected in plain radiography, the firstline diagnostic tool should be MDCT. In complicated cases or when biliary obstruction is suspected, CE-MRCP can give important morphological and physiological information regarding the whole abdomen and biliary system.

Kolesistoenterik fistüller, safra taşlarının %1’den daha az bir sıklıkta görünen komplikasyonlarındandır. Bouveret sendromu, mide çıkımında safra taşı/taşları tarafından oluşturulan tıkanıklık sonucu gelişir. Bu taşlar sıklıkla kolesistoenterik veya nadiren de kolesistogastrik fistül aracılığı ile mide çıkımını veya proksimal duedenumu tıkarlar.

Bouveret sendromunun erken tanı ve tedavisi, morbidite ve mortalitenin azaltılması için gereklidir. Bu olgu sunumunda, kolesistoenterik fistüllü ve Bouveret sendromlu bir hasta sunuldu. Bildiğimiz kadarıyla, çokkesitli bilgisayarlı tomografi (ÇKBT) (64 dedektörlü) ve kontrastlı manyetik rezonans (MR) kolanjiyopankreatografi (MRKP) ile Bouveret sendromu tanısı hakkında çalışma literatürde bulunmamaktadır. Amacımız kolesistoenterik fistüllerin saptanması ve değerlendirilmesinde ÇKBT ve kontrastlı MRKP etkinliğini tartışmaktır. ÇKBT ve kontrastlı MRKP ile safra yollarını fizyolojik olarak inceleyebildik ve biliyoenterik fistülü net olarak gösterdik. Ayrıca kontrastlı MRKP ile fizyolojik olarak safra sistemini değerlendirdik.

Sonuç olarak, bu tür olgularda ÇKBT, röntgen ve ultrasondan sonraki ilk tercih olmalıdır. Komplike veya safra tıkanıklığı şüphesi olan olgularda kontrastlı MRKP, tüm karın ve safra sistemi ile ilgili önemli morfolojik ve fizyolojik bilgileri verebilir.

Key Words: Bile ducts; Bouveret syndrome; fistula; gastric outlet obstruction; gallbladder; magnetic resonance cholangiography; multidetector row computed tomography; stone.

Anahtar Sözcükler: Safra yolları; Bouveret sendromu; fistül; mide çıkım obstrüksiyonu; safra kesesi; manyetik rezonans kolonanjiyografi; çok kesitli bilgisayarlı tomografi; safra taşı.

Departments of 1Radiology, 2General Surgery, Ataturk Training and Research Hospital, Ankara, Turkey.

Atatürk Eğitim ve Araştırma Hastanesi, Radyoloji Kliniği, 2Genel Cerrahi Kiliniği, Ankara.

1

Correspondence (İletişim): Oktay Algın, M.D. Atatürk Eğitim ve Araştırma Hastanesi, Radyoloji Kliniği, Ankara, Turkey.

Tel: +90 - 312 - 2912525 / 3240 e-mail (e-posta): droktayalgin@gmail.com

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Gallstone-induced ileus is a rare complication of cholelithiasis, and accounts for 1-3% of all cases with bowel obstruction.[1-3] Bouveret syndrome is a gastric outlet obstruction produced by gallstone(s) located in the distal stomach or proximal duodenum.[1] The route of gallstone migration to the bowel is most commonly via a cholecystoduodenal fistula; however, fistulization of the stomach is an infrequent variant.[2] In this report, we present a patient with cholecystogastric fistula and Bouveret syndrome. We show the exact localization of biliary stones and the relation of the biliary stones and the fistula by multidetector computed tomography (MDCT) and contrast-enhanced magnetic resonance cholangiopancreatography (CEMRCP). We also evaluated the biliary system with CE-MRCP physiologically. To our knowledge, there has been no previous report in the literature about a patient with Bouveret syndrome that was definitively diagnosed with MDCT (64 detectors) or CE-MRCP. Our aim was to discuss the efficacy of MDCT and CEMRCP in the detection and evaluation of cholecystenteric fistulas.

CASE REPORT An 88-year-old male patient, with no significant personal history, was admitted to the emergency department with the complaints of fever, nausea and pain in his right hypochondrium. Abdominal examination revealed sensitivity in the right upper quadrant and pain with palpation. Leukocytosis and elevated blood urea nitrogen, creatinine, transaminases, and alkaline phosphatase were detected in the laboratory tests. In plain radiography, multiple gallstones and biliary tree

air were detected. In the ultrasound (US) examination, the liver size was at the upper limit of normal, and an enlarged gallbladder filled with gallstones was observed. There was another 4x4 cm stone inferomedial to the gallbladder, in the neighborhood of the head of the pancreas and duodenum. Optimal abdominal US examination could not be performed due to poor cooperation of the patient. Since heterogeneity was detected in the gallbladder wall and in the head of the pancreas and the choledochus could not be detected in US examination, non-contrast-enhanced (NCE) abdominal MDCT was done to clarify a possible gallbladder perforation, ileus and acute biliary pancreatitis.

The MDCT scans with 64 detectors confirmed the presence of a 4x4 cm gallstone in the gastric pylorus, causing gastric outlet obstruction (Bouveret syndrome) and dilatation. In addition, there were a few stones in the gastric lumen, the largest being about 1 cm (Fig. 1). Diameter of the ductus choledochus was 13 mm, and intrahepatic bile ducts were minimally dilated. In the MDCT, the gallbladder content was heterogeneous and the gallbladder had penetrated the gastric pylorus. There was no pericholecystic fluid or acute pancreatitis.

In the upper gastrointestinal endoscopy, a gallstone obstructing the gastric pylorus was observed, but attempts to move the stone were unsuccessful. NCEMRCP was performed to evaluate the biliary system.

NCE-MCRP images were immediately evaluated by an experienced radiologist. Penetration of the gallbladder to the gastric wall, multiple gastric and cholecystic gallstones and gastric dilatation were demonstrated clearly (Fig. 2). However, the choledochal

Fig. 1. Coronal (on right and center) and sagittal (on left) reformatted MDCT images of the patient. MDCT images demonstrate pneumobilia (double-headed arrow), gastric distention, and antral (thick arrow) and pyloric (long arrow) stones.

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Bouveret syndrome

Fig. 2. Sequential coronal non-contrast-enhanced MRCP images show multiple gastric stones (thick arrow) and a large calculus impacted in the gastric pylorus (long arrow). There are several T2-weighted hypointensities in the ductus choledochus (short thin arrows).

lumen and obstruction in the biliary pathway could not be evaluated optimally. Thus, liver-specific contrast agent (0.1 ml/kg gadoxetic acid, Primovist, Schering, Germany) was given intravenously (IV). Images were taken at the 1st (portal phase), 20th (early-phase CEMRCP) and 40th (late-phase MRCP) minutes after IV administration of gadoxetic acid. No obstruction was detected in the biliary pathways and no choledochal stone was detected in CE-MRCP (Fig. 3).

Surgical treatment was planned. During surgery, the gallbladder was found to be fistulized into the gastric wall, and a stone measuring 4x4 cm in diameter was detected in this region. Cholecystectomy together with antrectomy followed by gastrojejunostomy were performed. There was full correlation between the surgical and radiological findings. The patient died on the 5th postoperative day due to cardiovascular problems.

DISCUSSION Cholecystenteric fistula is one of the rarest complications of biliary lithiasis, with a frequency of less than 1%.[1-3] Most are cholecystoduodenal fistulas (in 60% of cases), but cholecystocolic (in 17%), cholecystogastric (in 5%), and choledochoduodenal (in 5%) fistulas have been described as well.[4] Large stones passing through the fistula may cause intestinal obstruction, and this condition can be located in the terminal ileum (60%), proximal ileum and jejunum (20-40%), colon, and less frequently, stomach or duodenum, as detected in our case.[3] Bouveret syndrome is a special form of gastric outlet obstruction produced by impaction of a gallstone in the distal stomach or proximal duodenum.[4] It was described by Leon Bouveret in 1896 with upper abdominal pain, fever and emesis in an elderly patient with a history of biliary Cilt - Vol. 19 Say覺 - No. 4

pain.[1-4] The differential diagnosis of this syndrome includes gallstone ileus, perforated peptic ulcer disease, pancreatitis, and malignant fistula.[2] Size of the gallstone (2-8 cm), long history of biliary disease, repeated episodes of acute cholecystitis, female sex, and advanced age (over 60 years) have been described as risk factors for fistula formulation.[3] Early diagnosis of Bouveret syndrome or bilioenteric fistulas is important because the mortality rate has been reported to be as high as 30%, although it has decreased to 12% in recent years.[4] The high mortality may be related to advanced age, other comorbidities and complications of surgical intervention.[2] Plain radiographs, upper gastrointestinal fluoroscopy, and/or US examination can be useful in the diagnosis of Bouveret syndrome.[4] However, these techniques are diagnostic in about 50% of cases.[5,6] Endoscopic imaging can confirm the diagnosis and may provide a therapeutic modality.[1] Since patients with Bouveret syndrome are usually elderly and in poor general condition, these tests are insufficient and cannot give optimal results. This situation can result in a delay in diagnosis. CT or MDCT generally establishes the diagnosis of Bouveret syndrome.[7] As we experienced in our case, the choledochus lumen cannot be evaluated clearly using CT or MDCT in approximately 25% of the cases. On the other hand, NCEMRCP is a useful non-invasive tool for the evaluation of the whole biliary system and gastric/duodenal lumen. Also, NCE-MRCP clearly differentiates fluid from calculi, and can directly detect cholecystoduodenal fistula if there is enough fluid in the area.[4] As we observed in our patient, when complicated or obstructive biliary pathology is suspected, CE377

Ulus Travma Acil Cerrahi Derg

Fig. 3. Sequential axial contrast-enhanced MRCP images of the patient. There was no obstruction in the biliary system, the choledochus lumen is open, and there was no stone in the lumen (thin arrows). There were multiple stones and heterogeneous appearance in the gallbladder lumen (curved arrows). In the neighborhood of the inferior wall of the gallbladder, there was contrast-material enhancement and heterogeneous appearance (double-headed arrow). A calculus impacted in the gastric pylorus was seen next to this area (thick arrow).

MRCP can be useful for evaluating whether or not there is intrahepatic or extrahepatic obstruction. CEMRCP can be used for detection of pericholecystic inflammation and evaluation of the gallbladder, stomach and bowel walls.[8,9] In addition, in patients with renal insufficiency or impaired renal functions, use of gadoxetic acid is more convenient when compared with other MR contrast agents, because 50% of gadoxetic acid is eliminated by the liver. CE-MRCP is useful in the detection of other complications of cholelithiasis (such as gallbladder perforation) as well.[8] Open surgery, endoscopic removal and laparoscopic enterolithotomy have all been attempted for stone removal.[5] Although endoscopic removal is less invasive, it fails when the obstructing gallstone is very large. Fragmentation of calculi with endoscopic graspers can remove the blockage of the distal small bowel.

[7] The ideal treatment is to relieve the obstruction by 378

removing the offending gallstone, to close the fistula and prevent recurrences, and this can be achieved by open surgery.[3] In patients who are poor surgical candidates secondary to concomitant illnesses and advanced age, surgery is not preferred. If surgery is performed, enterolithotomy alone may be sufficient in such patients and a subsequent cholecystectomy may not be required.[2] In our patient, upper endoscopy was performed first. A stone obstructing the gastric pylorus and a fistula between the antrum and gallbladder were observed. All endoscopic attempts to move the stone were unsuccessful. Hence, surgery was the only opportunity for relieving the obstruction and preventing cholangitis, as well as to rule out gallbladder cancer. A semi-elective operation was performed, after completing fluid and electrolyte resuscitation and the obligatory consultations.

In conclusion, Bouveret syndrome is a very rare Temmuz - July 2013

Bouveret syndrome

variant of gallstone ileus. Early diagnosis is crucial to reduce morbidity and mortality. Therefore, when biliary lithiasis and ileus are detected in plain radiography, the first-line diagnostic tool should be MDCT. NCE-MRCP is useful for the morphological evaluation of the biliary system, but it cannot give physiological information. In complicated cases or when biliary obstruction is suspected, CE-MRCP can give important morphological and physiological information regarding the whole abdomen and biliary system.

Conflict-of-interest issues regarding the authorship or article: None declared.

4.

5.

6.

7.

REFERENCES 1. Puri V, Lee RW, Amirlak BA, Lanspa SJ, Fitzgibbons RJ Jr. Bouveret syndrome and gallstone ileus. Surg Laparosc Endosc Percutan Tech 2007;17:328-30.

2. Brennan GB, Rosenberg RD, Arora S. Bouveret syndrome.

Radiographics 2004;24:1171-5.

3. Iancu C, Bodea R, Al Hajjar N, Todea-Iancu D, Bălă O, Acalovschi I. Bouveret syndrome associated with acute gan-

Cilt - Vol. 19 Sayı - No. 4

8.

9.

grenous cholecystitis. J Gastrointestin Liver Dis 2008;17:8790.

Pickhardt PJ, Friedland JA, Hruza DS, Fisher AJ. Case report. CT, MR cholangiopancreatography, and endoscopy findings in Bouveret’s syndrome. AJR Am J Roentgenol 2003;180:1033-5.

Masannat YA, Caplin S, Brown T. A rare complication of a common disease: Bouveret syndrome, a case report. World J Gastroenterol 2006;12:2620-1.

Erlandson MD, Kim AW, Richter HM 3rd, Myers JA. Rouxen-Y duodenojejunostomy in the treatment of Bouveret syndrome. South Med J 2009;102:963-5.

O’Neill C, Colquhoun P, Schlachta CM, Etemad-Rezai R, Jayaraman S. Gastric outlet obstruction secondary to biliary calculi: 2 cases of Bouveret syndrome. Can J Surg 2009;52:E16-8.

Algin O, Ozlem N, Kilic E, Karaoglanoglu M, Arslan H. Gd-BOPTA-enhanced MR cholangiography findings in gall bladder perforation. Emerg Radiol 2010;17:487-91.

Algin O, Ozmen E, Ersoy PE, Karaoglanoglu M. Periampullary localized pancreatic intraepithelial neoplasia-3 (PanIN-3): evaluation with contrast-enhanced MR cholangiography (MRCP). Radiol Oncol 2011;45:300-3.

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Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):380-382

Case Report

Olgu Sunumu doi: 10.5505/tjtes.2013.37043

De Garengeot’s hernia: a case of acute appendicitis in a femoral hernia sac De Garengeot fıtığı: Femoral fıtık kesesi içinde bir akut apandisit olgusu Ceren ŞEN TANRIKULU,1 Yusuf TANRIKULU,2 Nezih AKKAPULU3

The presence of an appendix vermiformis in a femoral hernia sac is called De Garengeot’s hernia. It is a very rare clinical condition and requires emergency surgery. However, preoperative diagnosis of De Garengeot’s hernia is difficult. Herein, we report a 58-year-old female who presented with sudden-onset painful swelling in the right groin region. Diagnosis was established based on computed tomography findings, and appendectomy with meshfree hernia repair was performed. The postoperative period was uneventful, and the histopathologic examination of the specimen revealed gangrenous appendicitis.

Femoral fıtık kesesi içerisinde apendiksin bulunması de Garengeot fıtığı olarak adlandırılır. Bu klinik durum, oldukça nadir görülen ve acil cerrahi girişim gerektiren bir klinik durumdur ve De Garengeot fıtığı tanısının ameliyat öncesi konulması oldukça zordur. Bu yazıda sunulan olgu sağ kasık bölgesinde aniden başlayan ağrısı olan 58 yaşında kadın hastadır. Tanı, bilgisayarlı tomografi bulguları ile konuldu ve apendektomiyle birlikte greftsiz fıtık onarımı uygulandı. Ameliyat sonrası komplikasyon gelişmedi.

Histopatolojik inceleme gangrenöz apandisit ile uyumluydu.

Key Words: Appendicitis; De Garengeot’s hernia; femoral hernia; hernia.

Anahtar Sözcükler: Apandisit; De Garengeot fıtığı; femoral fıtık; fıtık.

The presence of appendix vermiformis in a femoral hernia sac is quite a rare entity. It was first described

by Rene Jacques Croissant de Garengeot in the 18th century, and this entity was later designated as “De Garengeot’s hernia”. The incidence of this disease is estimated to range approximately from 0.5 to 5% and is seen more commonly in women.[1-3]

palpation. Her bowel sounds were normoactive, and there was no sign of acute abdomen. Her body temperature was 38 °C, and white blood cell count (WBC) was 14500/mm3; other laboratory findings were within normal limits. Abdominal computed tomography (CT) imaging was compatible with appendicitis in a femoral hernia sac (Fig. 1).

CASE REPORT A 58-year-old female patient was admitted to our emergency clinic with the complaint of sudden onset of nausea, vomiting and painful swelling in the right groin region for the last 24 hours. The patient was hemodynamically stable, and clinical examination revealed a 3x4 cm mass in the right groin region. She had tenderness over this mass, and it was irreducible on

She was diagnosed with irreducible right femoral hernia. An emergent surgery was planned. Through a right suprainguinal incision, the inguinal canal was opened, and the transversalis fascia was transected.

After the femoral hernia sac was found and isolated from surrounding structures, it was opened, and an inflamed and gangrenous appendix vermiformis was found in the sac (Fig. 2). The proximal tip of the ap-

Departments of 1Emergency Department, 2General Surgery, Erzurum Training and Research Hospital, Erzurum; 3 Department of General Surgery, Muş State Hospital, Muş, Turkey.

Erzurum Bölge Eğitim ve Araştırma Hastanesi, 1Acil Tıp Kliniği, 2 Genel Cerrahi Kliniği, Erzurum; 3 Muş Devlet Hastanesi, Genel Cerrahi Kliniği, Muş.

Correspondence (İletişim): Nezih Akkapulu, M.D. Muş Devlet Hastanesi, Genel Cerrahi Kliniği, 49100 Muş, Turkey.

Tel: +90 - 436 - 212 28 04 e-mail (e-posta): akkapulu@gmail.com

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Many theories have been suggested for the pathogenesis of de Garengeot’s hernia. The most widely accepted is the congenital theory, according to which, pelvic localization of the appendix vermiformis and rigid femoral ring predispose to the development of de Garengeot’s hernia.[6-8]

Fig. 1. Inflamed appendix in the hernia sac is shown with arrow on computed tomography scan.

pendix and cecum were found by tracing the appendix, and appendectomy was performed. The femoral hernia was repaired with McVay’s technique after the hernia sac was excised intraabdominally. The incision was closed according to anatomical planes. Postoperative follow-up was uneventful, and the patient was discharged on the second postoperative day.

DISCUSSION Rene Jacques Croissant de Garengeot first described the presence of the appendix vermiformis in a femoral hernia sac in 1731, and this entity was later designated as “De Garengeot’s hernia”.[1,2] The appendix in a femoral hernia sac may be of three types, as normal, inflamed or gangrenous.[4] De Garengeot’s hernia is quite a rare entity, and is seen more frequently in women than men, with a ratio of 3:1. The incidence of this disease is estimated to range approximately from 0.5 to 5% during femoral hernia repairs.[1,3] Sharma et al.[5] reported the mean age of patients with de Garengeot’s hernia as 55 years.

Appendicitis

Hernia sac

Fig. 2. Intra-operative view of De Garengeot’s hernia.

(Color figure can be viewed in the online issue, which is available at www.tjtes.org).

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De Garengeot’s hernia is usually determined intraoperatively, but can be detected preoperatively by radiologic evaluation such as with CT.[9] In the literature, 98% sensitivity and specificity have been reported for CT scan.[10] Emergent surgery is the definitive treatment of de Garengeot’s hernia. During surgery, appendectomy and femoral hernia repair are performed consecutively. Many tension or tension-free methods have been described for the repair of a femoral hernia according to the usage or not of prosthetic meshes. The most common method for femoral hernia is Cooper’s ligament repair (McVay’s technique).[5,11,12] Mesh utilization should be avoided in the presence of inflammation and infection. The femoral hernia can be repaired with non-absorbable suture materials.[13] In conclusion, acute appendicitis within a femoral hernia can be a life-threatening condition and always requires emergency surgery. Abdominal CT scan can be helpful in the diagnosis in the absence of abdominal findings of acute appendicitis. Appendectomy with mesh-free hernia repair is an acceptable treatment for de Garengeot’s hernia.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Akopian G, Alexander M. De Garengeot hernia: appendicitis within a femoral hernia. Am Surg 2005;71:526-7.

2. Tanner N. Strangulated femoral hernia appendix with perforated sigmoid diverticulitis. Proc R Soc Med 1963;56:11056.

3. Gurer A, Ozdogan M, Ozlem N, Yildirim A, Kulacoglu H, Aydin R. Uncommon content in groin hernia sac. Hernia 2006;10:152-5.

4. Fitzgerald E, Neary P, Conlon KC. An unusual case of appendicitis. Ir J Med Sci 2005;174:65-6.

5. Sharma H, Jha PK, Shekhawat NS, Memon B, Memon MA. De Garengeot hernia: an analysis of our experience. Hernia 2007;11:235-8.

6. D’Ambrosio N, Katz D, Hines J. Perforated appendix within a femoral hernia. AJR Am J Roentgenol 2006;186:906-7.

7. Nguyen ET, Komenaka IK. Strangulated femoral hernia containing a perforated appendix. Can J Surg 2004;47:68-9.

8. Temple CL, Huchcroft SA, Temple WJ. The natural history of appendicitis in adults. A prospective study. Ann Surg 1995;221:278-81.

9. Zissin R, Brautbar O, Shapiro-Feinberg M. CT diagnosis of acute appendicitis in a femoral hernia. Br J Radiol 2000;73:1013-4.

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10. Rao PM, Rhea JT, Novelline RA, Mostafavi AA, McCabe CJ. Effect of computed tomography of the appendix on treatment of patients and use of hospital resources. N Engl J Med 1998;338:141-6.

11. Carey LC. Acute appendicitis occurring in hernias: a report of 10 cases. Surgery 1967;61:236-8.

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12. Rose RH, Cosgrove JM. Perforated appendix in the incarcerated femoral hernia. A place for preperitoneal repair. N Y State J Med 1988;88:600-2.

13. Korenkov M, Paul A, Troidl H. Color duplex sonography: diagnostic tool in the differentiation of inguinal hernias. J Ultrasound Med 1999;18:565-8.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):383-384

Case Report

Olgu Sunumu doi: 10.5505/tjtes.2013.44522

Severe burn on 81% of body surface after sun tanning Güneşte bronzlaşma sonrası vücut yüzeyinin %81’inde ağır yanık Marcos SFORZA,1 Katarina ANDJELKOV,2 Renato ZACCHEDDU3

We report herein the case of a 42-year-old woman who presented to the Burns Unit with 81% of her body surface severely burned following sun bathing, after applying fig leaf tea as a tanning agent. The patient was hospitalized for 13 days in a Burns Intensive Care Unit, and was discharged for an ambulatory follow-up. The treatment of such burns does not differ from any conventional treatment for heatinduced second-degree burns. The physiopathology of the phytophotodermatitis induced by such homemade tanning solutions rich in psoralen is discussed in detail.

Bu yazıda 42 yaşında, bronzlaşmak için incir yaprağı çayı sürmüş ve güneş banyosu sonrası vücudunun %81’i ağır biçimde yanmış halde yanık ünitesine gelmiş bir olgu sunuldu. Hasta yanık ünitesinin yoğun bakımında 13 gün yattı ve ayaktan takip için taburcu edildi. Bu tip yanıkların tedavisi, ikinci derece sıcaktan yanıkların konvansiyonel tedavisinden farklı değildir. Böyle ev yapımı yoğun psoralen içeren bronzlaştırıcı çözeltilerin tetiklediği fitofotodermatitin fizyopatolojisi ayrıntılı tartışılmaktadır.

Key Words: Burns; fig leaf; phytophotodermatitis.

Anahtar Sözcükler: Yanıklar; incir yaprağı; fitofotodermatit.

The amount of solar radiation absorbed by the skin can induce skin burn. Normally, first-degree burns are the most common after sun tanning. The use of tanning-facilitating agents can accelerate this process, causing deeper and more severe damage.

before. The patient also reported to be suffering from severe pain, dehydration and nausea with associated vomiting.

Sun tanning is routine in tropical countries. The use of tanning agents to help obtain the “perfect tan” is also a common practice. The ideal product should contain moisturizing and solar protection agents. As these products are substantially more expensive, the poorer segments of the population usually improvise with dangerous homemade solutions.

We report herein a case with severe and extensive sunburn (81% of the body surface) due to the use of a homemade solution using fig leaf tea as a tanning agent.

CASE REPORT A 42-year-old woman was taken to the Burns Unit with a history of sun tanning using fig leaf tea 24 hours

UNIFESO School of Medicine, Rio de Janeiro, Brasil; 2 Belmedic Hospital, Belgrade, Serbia; 3 Dolan Park Hospital, Milan, Italy.

1

On the physical examination, 81% of the patient’s body surface was burned (according to Lund-Browder scale), with the majority being second-degree and with no third-degree associated burn (Fig. 1a). The patient was diagnosed with severe skin burn and was admitted to the Burns Intensive Care Unit.

Deep venous catheterization was performed immediately, and the patient was subjected to a rehydration protocol (Carvajal) and underwent mechanical debridement under deep sedation (Fig. 1b).

The mechanical cleaning of burn patients is conducted by a plastic surgeon with the assistance of a nurse and an anesthesiologist responsible for the sedation. In our unit, the dressing changes are done in the mornings with additional afternoon dressings when necessary. Propofol and ketamine are used for seda-

UNIFESO Tıp Fakültesi, Rio de Janeiro, Brezilya; 2 Belmedic Hastanesi, Belgrad, Sırbistan; 3 Dolan Park Hastanesi, Milano, İtalya.

1

Correspondence (İletişim): Marcos Sforza, M.D. 65 Liberty Place, Sheepcote St., Birmingham, United Kingdom.

Tel: +44 - 798 - 412 22 60 e-mail (e-posta): drmarcossforza@gmail.com

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cal areas. The fig leaf (Ficus carica) is rich in psoralen, which is the active substance responsible for the stronger and deeper tan effect.[3,4] Psoralens intercalate in DNA, but do not establish covalent bonds in absence of light. Under the effect of light, the psoralens intercalated in DNA are activated, even in the absence of oxygen, and establish intra- or inter-strand covalent bonds with bases, forming adducts. In the presence of oxygen, there is, in addition, formation of superoxide radicals that damage DNA. By these two mechanisms, psoralens, under the influence of light, inhibit replication and transcription.

They increase pigmentation by acting on melanocytes, as a very strong photosensitizing agent.[5]

(a)

(b) Fig. 1. (a) 81% of the patient’s body surface was burned, and (b) underwent mechanical debridement under deep sedation. (Color figures can be viewed in the online issue, which is available at www.tjtes.org).

tion. Ketamine induces an effective hypnotic as well as anesthetic effect, but demands an experienced anesthetist for its management.

The dressing procedures applied to this patient were the same as with any other second-degree burn injury caused by heat. This patient needed only morning dressing changes on a daily basis. The occlusive dressings were made with 4-amino-N-(2-pyrimidinyl) benzenesulfonamide silver salt cream (also known as silver sulfadiazine or Dermazine®) for the first 7 days.

The silver sulfadiazine acts as an antiviral, antibactericidal and antifungal agent until the natural process of re-epithelization begins. After the body was able to reinstall its own natural barriers, the occlusive dressings were changed to Vaseline until she was released from the Burns Unit. This patient did not require any skin grafts and did not develop any skin infection during the process. The patient was hospitalized for 13 days and was discharged for complementary ambulatory follow-up when fully re-epithelized.

DISCUSSION Various substances in third-world countries are used for tanning by the poor population.[1] A mix of the fig leaf’s tea with a mineral oil is a quite common homemade tanning solution.[2] The fig tree is a bearer tree of the Moraceae family, commonly found in tropi384

Fortunately, the burn injury caused by this agent can be treated easily in any hospital as any burn inflicted by heat. The fig leaf does not lead to any specific chemical burn per se. Moreover, it mainly precipitates sunburn by allowing the sun radiation to promote a severe phytophotodermatitis in over-photosensitized skin. As illustrated in this unique case, the treatment of this particular burn fortunately does not differ from that of any severe heat-induced burn.

In Brazil, several hospitals reported more than 50 cases of fig leaf-induced burn, in one summer, exclusively in their areas. The easy access to the components and the almost zero cost make this a very attractive practice. There are no reports of death caused by these burns thus far.[6] The official agencies in these countries are already developing education campaigns to try to alert the population to the risks of this practice. However, reports in the medical literature are increasing every year.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Piccolo-Lobo MS, Piccolo NS, Piccolo-Daher MT, Cardoso VM. Sun tanning-related burns-a 3-year experience. Burns 1992;18:103-6.

2. Bollero D, Stella M, Rivolin A, Cassano P, Risso D, Vanzetti M. Fig leaf tanning lotion and sun-related burns: case reports. Burns 2001;27:777-9.

3. Zaynoun ST, Aftimos BG, Abi Ali L, Tenekjian KK, Khalidi U, Kurban AK. Ficus carica; isolation and quantification of the photoactive components. Contact Dermatitis 1984;11:21-5.

4. Vaya J, Mahmood S. Flavonoid content in leaf extracts of the fig (Ficus carica L.), carob (Ceratonia siliqua L.) and pistachio (Pistacia lentiscus L.). Biofactors 2006;28:169-75.

5. Polat M, Oztas P, Dikilitas MC, Alli N. Phytophotodermatitis due to Ficus carica. Dermatol Online J 2008;14:9.

6. Micali G, Nasca MR, Musumeci ML. Severe phototoxic reaction secondary to the application of a fig leaves’ decoction used as a tanning agent. Contact Dermatitis 1995;33:212-3.

7. Ozdamar E, Ozbek S, Akin S. An unusual cause of burn injury: fig leaf decoction used as a remedy for a dermatitis of unknown etiology. J Burn Care Rehabil 2003;24:229-33.

Temmuz - July 2013

Turkish Journal of Trauma & Emergency Surgery

Ulus Travma Acil Cerrahi Derg 2013;19 (4):385-386

Case Report

Olgu Sunumu doi: 10.5505/tjtes.2013.67424

An extremely rare appendiceal anomaly: horseshoe appendicitis Apendiksin çok nadir bir anomalisi: At nalı apandisit Cem ORUÇ,1 Özgen IŞIK,1 Orhan ÜREYEN,1 Oytun Saffet KAHYAOĞLU,1 Ayhan KÖSEOĞLU2

Appendiceal anomalies are extremely rare malformations that are usually found in adult populations as an incidental finding. Agenesis and duplication of the appendix have been well documented, but we know of only three reported cases of a horseshoe appendix. A 64-year-old woman admitted to the emergency department. A provisional diagnosis of acute appendicitis was made, and the patient was taken to the operating room. While appendectomy was being performed with a standard approach, the distal tip was seen to communicate with the cecum by another stump, or “horseshoe appendix”. The aim of this report is to share our experience with this extraordinary finding.

Key Words: Appendix vermiformis; horseshoe; malformation.

Appendiceal anomalies are extremely rare malformations that are usually found in adult populations as an incidental finding. Agenesis and duplication of the appendix have been well documented, and the incidences for these anomalies are 0.008% and 0.004%, respectively.[1] However, we know of only three reported cases of a horseshoe appendix.[2-4] In this report, we present the fourth case of a horseshoe appendix.

CASE REPORT A 64-year-old woman admitted to the emergency department with a two-day history of right lower abdominal pain, nausea, and loss of appetite. The abdominal examination revealed right lower quadrant tenderness, guarding and rebound tenderness at McBurney’s point. All laboratory study results were in normal ranges, and plain chest and abdominal ra-

Departments of 1General Surgery, 2Anesthesiology and Reanimation, İdil State Hospital, Şırnak, Turkey.

Apendiks anomalileri çoğunlukla erişkin popülasyonda rastlantı sonucu bulunan çok nadir malformasyonlardır.

Apendiks agenezis ve duplikasyonu iyi bilinmesine rağmen, bildirilmiş sadece üç adet atnalı apendiks olgusu bulunduğunu biliyoruz. Acil servise başvuran 64 yaşında kadın hasta akut apandisit ön tanısı ile ameliyathaneye alındı. Standart yaklaşımla apendektomi uygulanırken, “at nalı apendiks” şeklinde distal ucun ikinci bir güdük ile çekumla bağlantılı olduğu görüldü. Buradaki amacımız bu sıra dışı bulguyla ilgili deneyimimizi paylaşmaktır.

Anahtar Sözcükler: Appendiks vermiformis; at nalı; malformasyon.

diographs showed no abnormality. Ultrasonographic examination determined pericecal minimal fluid collection. A provisional diagnosis of acute appendicitis was made, and the patient was taken to the operating room. A standard approach was taken with incision over McBurney’s point. The cecum was identified, the taenia coli were followed to their confluence, and an appendiceal stump was found. The distal appendiceal tip was seen to extend to the posteromedial cecum, and there were adhesions that complicated mobilization of the appendix. A decision was made to perform retrograde appendectomy. After appendiceal stump and mesoappendix were ligated and divided, the distal tip was seen to communicate with the cecum by another stump, or “horseshoe appendix” (Figs. 1a, b). Appendectomy was completed. The patient made an uneventful recovery and was discharged two days later.

İdil Devlet Hastanesi, 1Genel Cerrahi Kliniği, Anesteziyoloji ve Reanimasyon Kliniği, Şırnak.

2

Correspondence (İletişim): Özgen Işık, M.D. İdil Devlet Hastanesi, İdil 73300 Şırnak, Turkey.

Tel: +90 - 486 - 551 36 36 e-mail (e-posta): ozgenisik@uludag.edu.tr

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(a)

(b)

Fig. 1. (a, b) Horseshoe appendix. (Color figure can be viewed in the online issue, which is available at www.tjtes.org).

DISCUSSION Appendiceal anomalies are extremely rare malformations. In the study of Collins[1] on 50,000 appendix specimens, there were only four cases of agenesis and two of duplication. Appendiceal duplications were first classified by Cave in 1936 by their anatomical location; this was updated and modified in 1963 by Wallbridge.[3,4] Although several other authors have added further modifications to the classification, it continues to be used for classification of appendiceal duplications only. More recently, cases that do not fit into this classification system have been described as the “horseshoe appendix” or “triple appendix”.[5] We thus believe either a new classification system is needed to design appendiceal anomalies, or the present system should be modified. Previously reported horseshoe appendix cases have either been diagnosed during interval appendectomy or found incidentally during abdominal surgery for other reasons. This appendiceal anomaly is likely the result of some unknown embryologic event. Perhaps during embryologic life, the single appendiceal base somehow split in two and become further separated during cecal growth. This might account for just such a double-based, yet single,

386

structure.[2] An appendiceal anomaly can be associated with other congenital abnormalities.[3-5] Preoperative radiological diagnosis of appendiceal anomalies is uncommon. Because of its particular rarity, most surgeons will never encounter a case of horseshoe appendix. It is therefore important that surgical trainees are aware of the anatomical anomalies and malpositions of the appendix.

Conflict-of-interest issues regarding the authorship or article: None declared.

REFERENCES 1. Collins DC. A study of 50,000 specimens of the human vermiform appendix. Surg Gynecol Obstet 1955;101:437-45.

2. Mesko TW, Lugo R, Breitholtz T. Horseshoe anomaly of the appendix: a previously undescribed entity. Surgery 1989;106:563-6.

3. DasGupta R, Reber PU, Patel AG. Horseshoe appendicitis.

Eur J Surg 1999;165:1095-6.

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Temmuz - July 2013