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05. Kenji Inaba Turkish Journal of Trauma & Emergency Surgery Ulus Travma Acil Cerrahi Derg 2008;14(3):175-181 Review Derleme Local and systemic hemostatics in trauma: a review Travmada lokal ve sistemik hemostatik ajanlar: Derleme yaz›s› Gustavo RECINOS,1 Kenji INABA,1 Joseph DUBOSE,1 Demetrios DEMETRIADES,1 Peter RHEE2 Hemorrhage is the leading cause of trauma-related deaths. The Kanama, travma ile iliflkili ölümlerin baflta gelen nedenidir. early identification and surgical control of this hemorrhage is Kanaman›n erken tan›s› ve cerrahi kontrolü, travmal› hastan›n the crucial first step in the management of the injured patient; tedavisinin düzenlenmesinde kritik ilk ad›md›r; ne var ki bu however, this objective remains challenging in the most criti- amaca ulaflmak, ileri derecede kritik travma hastalar›nda hala cally ill trauma patients. As an adjunct to traditional methods ciddi bir sorun olagelmektedir. Geleneksel cerrahi kanama of surgical hemorrhage control, several advanced hemostatic kontrolü yöntemlerine ek olarak, günümüzde baz› ileri hemos- agents are currently available. Oxidized cellulose, fibrin glue tatik ajanlar da kullan›lmaktad›r. Oksidize selüloz, fibrin ya- and synthetic adhesives constitute the first-line of local hemo- p›flt›r›c› ile sentetik yap›flt›r›c›lar, lokal hemostatik ajanlar›n static agents. Materials such as Zeolite and Chitosan comprise öncelikli grubunu oluflturmaktad›r. Zeolite ve Chitosan, lokal the newest generation of local hemostatics and the efficacy hemostatiklerin en yeni jenerasyonunu oluflturur ve bu ajanla- and safety of these agents are currently under investigation. r›n etkinli¤i ve güvenilirli¤i halen araflt›rma aflamas›ndad›r. Recombinant factor VIIa has emerged recently as a promising Rekombinant faktör VIIa yak›n zamanda, kontrol alt›na al›na- systemic hemostatic adjunct for the treatment of intractable mayan cerrahi kanaman›n tedavisine yard›mc›, ümit verici bir surgical bleeding; however, until completion of the ongoing sistemik hemostatik ajan olarak ortaya ç›km›flt›r; ancak devam multinational randomized control trial, the indications for its eden çok uluslu randomize kontrollü çal›flma tamamlan›ncaya use in trauma patients and its safety profile are unclear. This kadar rekombinant faktör VIIa’n›n travma hastalar›ndaki kul- article reviews the role of commercially available local and lan›m› ile ilgili endikasyonlar ve güvenilirlik profili belirsiz- systemic hemostatic products in the trauma patient popula- dir. Bu yaz›da, ticari olarak mevcut bulunan lokal ve sistemik tion; it also addresses the unique set of characteristics, indica- hemostatik ürünlerin travma hastalar›ndaki rolü gözden geçi- tions, limitations and rationale for their use. rildi; ayn› zamanda bunlar›n ak›lc› kullan›m›yla ilgili benzer- siz özelliklerle endikasyon ve k›s›tlamalar de¤erlendirildi. Key Words: Coagulopathy; hemorrhage; hemostatics; trauma. Anahtar Sözcükler: Hemostatik; kanama; koagülopati; travma. Introduction hypothermia-induced platelet dysfunction.[2] T h e Hemorrhage is the leading cause of preventable prevention of coagulopathy after trauma requires mortality after injury.[1] Coagulopathy, commonly both prompt surgical control of hemorrhage and the associated with trauma, contributes significantly to maintenance of an appropriate homeostatic milieu hemorrhagic blood loss and is the sum result of a for effective functioning of the coagulation system. number of contributing mechanisms. These include A variety of local and systemic adjuncts can be uti- hemodilution of factors and platelets during resus- lized to support these efforts, including several citation, coagulation factor consumption and advanced pharmacological hemostatic treatments. 1Department of Surgery, Division of Trauma and Critical Care, 1Güney Kaliforniya Üniversitesi, Cerrahi Anabilim Dal›, Travma ve Yo¤un University of Southern California, Los Angeles, California; 2Department of Bak›m Bölümü, Los Angeles, Kaliforniya; Surgery, Division of Trauma and Critical Care, University of Arizona, 2Arizona Üniversitesi, Cerrahi Anabilim Dal›, Travma ve Yo¤un Bak›m Tucson, Arizona, USA. Bölümü, Tuscon, Arizona, ABD. Correspondence (‹letiflim): Kenji Inaba, M.D. 1200 N. State Street, 90033 Los Angeles, United States. Tel: +1 (323) 226 81 12 Fax ( F a k s ): +1 (323) 2 2 6 8 1 1 6 e-mail ( e - p o s t a ) : k i n a b a @ s u r g e r y . u s c . e d u 175 Ulus Travma Acil Cerrahi Derg Local hemostatics use of these local hemostatics also warrant careful As an adjunct to traditional methods of surgical consideration. Injury to nerves, ureters and other hemorrhage control, a wide spectrum of hemostatic specialized structures due to local desiccation, agents is currently available. Each of the commer- ischemia due to compression, or local inflammato- cially available products has its own unique charac- ry reaction may be under-appreciated. Brodbelt et teristics, and it is essential that surgeons employing al. have reported three cases of local neurological sequelae after the use of oxidized cellulose in tho- such materials be familiar with their benefits and [4] limitations. Traditionally employed local hemostatic racic surgery. It is therefore advisable that caution agents include cellulose-based products, fibrin and be taken when applying these adjuncts in proximi- synthetic glues. More recently, the effectiveness of ty to such structures, and excess material not con- tributing to hemostasis should be removed, if possi- newer products, such as Chitosan and Zeolite, are being investigated in ongoing trials to examine the ble, at subsequent re-operation following damage control procedures. utility of this newer generation of local hemostatic agents. Another frequently discussed potential compli- cation of local hemostatic use is that of infection. It Cellulose-based hemostatics has been theorized that these substances may serve Some of the most widely available and com- as a nidus for bacterial adherence and promote monly utilized hemostatic agents are derived from infection and abscess formation, particularly in the oxidized cellulose, commercially available in the heme-rich environment in which they are US as Surgicel© and Nu-Knit© (Ethicon, Inc., employed. Despite these concerns, it has actually Cincinnati, OH). This class of agent is intended for been observed that oxidized regenerated cellulose use as an adjunct to gauze packing, with their hemo- may confer some protective bacterial resistance static properties primarily based on their ability to against a wide variety of pathogenic organisms.[5,6] locally activate the coagulation cascade. While they This effect has been attributed to the decrease in pH do not contain any intrinsic coagulation compo- associated with the use of this agent, a change in the nents, they are designed to stimulate clot formation local milieu that hinders bacterial proliferation. and to provide a favorable three-dimensional struc- ture for clot organization. In order for these prod- Fibrin adhesives ucts to function, therefore, a functional coagulation Fibrin adhesives are a group of biological tissue system must be present. In a study by Krizova and adhesives composed of thrombin and purified colleagues, the investigators demonstrated that a human or bovine fibrinogen that mimic the final local hemostatic comprised of oxidized cellulose step of the physiologic coagulation cascade, failed to induce platelet activation in the absence of depositing a fibrin-rich clot at the site of applica- plasma constituents, especially factors VIII and tion. The use of fibrin-based adhesives has been XII.[3] well examined in both animal and human studies. Commercially available in many forms (Tisseel™, These cellulose-based products have distinctive Floseal™, Baxter Inc., Deerfield, IL), differing in potential limitations that should be considered prior their source components and physical characteris- to their use. Their effective deployment may prove tics, these products have been proposed for use in a difficult in wet environments, due to their poor wide variety of surgical subspecialty settings, as adhesion to tissue in this setting. Frequently, the well as in humans with hemophilia and other bleed- application of adequate pressure at the site of hem- ing disorders.[7-13] Various animal models have also orrhage is also required to provide the tamponade shown successful control of bleeding in the pres- necessary to facilitate their effectiveness. Given the ence of coagulopathy. Holcomb et al. found that, fact that this range of products relies on an intact after creating a grade V liver injury in a hemodilut- coagulation mechanism, their utility in coagulo- ed, hypothermic coagulopathic swine model, the pathic patients is also limited. For these reasons, use of fibrin-based sealants provided rapid hemor- cellulose-based products should be utilized only to rhage control, decreased fluid requirements and assist in the local control of mild hemorrhage. improved survival.[11] In another animal model of Potential local complications associated with the liver injury, Feinstein and colleagues concluded 176 Temmuz - July 2008 Local and systemic hemostatics in trauma: a review that the use of fibrin adhesives in heparinized swine clot formation. This material is, however, only rapidly controlled hemorrhage and eliminated the Food and Drug Administration (FDA)-approved for need for packing.[12] external use at the present time. Several human studies have also provided evi- In animal models of external bleeding, dence for the efficacy of fibrin-based
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