NATO Medical Conference Comparison of Four Hemostatic Agents in Control of Extremity Hemorrhage in a Model of Penetrating Trauma NATO Medical Conference Lisbon, Portugal October 1, 2009 Lanny Littlejohn, MD LCDR MC (FS/DMO) USN NMCP Dept of Emergency Medicine Medical Director, TCCC

Acknowledgements This study was funded by SAM Medical Products® Portland, Oregon (unrestricted grant). None of the authors have received salary from, or are spokespersons for, the funding company. The views expressed in this presentation are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government

However, which agent is superior remains unclear. The Problem Uncontrolled Hemorrhage Causes Unnecessary Death Leading cause of death in combat trauma Second leading cause of death in civilian trauma Hemostatic Agents hold great potential …in early control of bleeding when tourniquets cannot be used However.. Combat medics report... commonly deployed agents less efficacious in smaller wounds (Devlin, 2009) Various Agents are available Standard Gauze dressing (SD) CELOX-A (CA) Chitoflex (CF) Combat Gauze (CG) WoundStat (WS) However, which agent is superior remains unclear.

Historical Background Colonel Bellamy looked at how soldiers died in ground combat and identified 3 major areas of preventable combat death. 1) Airway obstruction from simply being unconscious or from facial trauma. 2) Tension pneumothorax from penetrating injury to the chest. And 3) Exsanguination from extremity wounds. This 9% represents largely preventable deaths. From: Bellamy, RF. The cause of death in conventional land warfare. Military Medicine .1984

Study Objectives Conduct a randomized, prospective, controlled trial in a clinically relevant model of penetrating trauma To assess the equivalence of 4 hemostatic agents compared to standard gauze dressing. Primary endpoints Achievement of Initial Hemostasis Incidence of Rebleeding Survival

Agents Tested CELOX-A (CA) Chitosan powder “A” = applicator ChitoFlex (CF): Chitosan rolled gauze forms a sticky mucoadhesive barrier at the site of bleeding cationic charge interacts with negatively charged red cell membrane Pilot study was conducted on 8 animals to familiarize investigators with the use of the various hemostatic agents impregnated with Kaolin, a powerful activator of the intrinsic pathway of coagulation Granular Smectite (clay) activates intrinsic hemostatic pathway molded into a firm clay at site of injury Combat Gauze (CG) Kaelin impregnated gauze WoundStat (WS) Smectite based granules

Compliance with Ethical Guidelines Test Subjects Swine (sus scrofa) (N = 80) randomized into 5 treatment arms (n=16 per arm) similar across groups in weight (43kg, SD=7.7) and baseline hemodynamics Protocol 2009.0037 was approved by the institution animal care and utilization committee Compliance with Ethical Guidelines

Injury: Designed to simulate penetrating trauma w/ vessel injury Study Protocol Injury: Designed to simulate penetrating trauma w/ vessel injury Limited Access injury linear tract (3 cm) Right groin tunneled tract to large exit wound Complete Transection Of the vascular bundle with #20 scalpel 45 second bleed 23.9 ml/kg (35% blood volume) Apply agents w/ pressure for 5 min Resuscitate with colloid 10 min after injury Monitor for 3 hours

Injury & Randomization Design Timeline Pigs N = 80 CELOX-A n = 16 Injury & Randomization CHITOFLEX COMBAT GAUZE WOUNDSTAT Survival? Necropsy to ensure similar wounding pattern Time Treatment Observation STANDARD GAUZE 180 min Initial Hemostasis Rebleeding 15 min Baseline Vitals Follow-up Statistical Analysis ANOVA Kruskal Wallis p < .05

Mean Arterial Pressure

Results Initial Hemostasis

Incidence of Rebleeding Results Incidence of Rebleeding

Results Survival

Observations CELOX-A: May only need 1 injector ChitoFlex: Must completely unroll Combat Gauze: 4 foot roll takes Time to completely pack WoundStat: Over half packed manually Into wound

Practical Implications CELOX-A best alternative where initial hemostasis is crucial: Far forward Combat Environment Remote locations (Wilderness, Rural) Mass Casualty (little time to spend per patient) Gauze products reasonable when: Evacuation times short (most civilian EMS systems) Single patient (more time to spend on basic wound care)

Conclusions CELOX-A Chitoflex WoundStat Ý initial hemostasis over other agents except CombatGauze Chitoflex Ý incidence of rebleeding WoundStat Ý mortality Standard dressing worked reasonably well no significant increase in mortality.

Comparison of Four Hemostatic Agents in Control of Extremity Hemorrhage in a Model of Penetrating Trauma Lanny F. Littlejohn, MD LCDR MC USN Assistant Investigators: John Devlin, MD Sara Kircher, BS Robert Lueken, MD Michael Melia, MD Andrew Johnson, MD Veterinarian: Len Murray, DVM Statistical Analysis: Gregory J Zarow,PhD