1. 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

2. 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

3. 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.

4. 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

5. 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

6. 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

7. 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 was approved by the institution animal care and utilization committee
Compliance with Ethical Guidelines

8. 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

9. 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

10. Mean Arterial Pressure

11. Results
Initial Hemostasis

12. Incidence of Rebleeding
Results
Incidence of Rebleeding

13. Results
Survival

14. 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

15. 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)

16. 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.

17. 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