Lanny Littlejohn, Lanny Littlejohn, MDMD

LCDR MC (FS/DMO) USNNMCP Dept of Emergency Medicine

Medical Director, TCCC

NATO Medical NATO Medical Conference Conference

Lisbon, Portugal Lisbon, Portugal October 1, 2009October 1, 2009

Comparison of Four Hemostatic Agents in Control of Extremity

Hemorrhage in a Model of Penetrating Trauma

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

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 BackgroundHistorical Background

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 TestedCELOX-A (CA)

Chitosan powder“A” = applicator

Combat Gauze (CG)Kaelin impregnated gauze

ChitoFlex (CF): Chitosan rolled gauze

WoundStat (WS)Smectite based granules

cationic charge interacts with

negatively charged red cell membrane

forms a sticky mucoadhesive barrier at the site of bleeding

Granular Smectite (clay) activates

intrinsic hemostatic pathway

molded into a firm clay at site of injury

impregnated with Kaolin, a powerful

activator of the intrinsic pathway

of coagulation

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

Study Protocol

• 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: Designed to simulate penetrating trauma w/ vessel injury Injury: Designed to simulate penetrating trauma w/ vessel injury

Design Timeline

PigsN = 80

CELOX-An = 16

Injury & Randomization

CHITOFLEXn = 16

COMBAT GAUZEn = 16

WOUNDSTAT n = 16

Survival?Necropsy

to ensure similar wounding pattern

Time

Treatment Observation

STANDARD GAUZE

n = 16

180 min

Initial HemostasisRebleeding

15 min

BaselineVitals

Follow-up

Statistical AnalysisANOVA

Kruskal Wallisp < .05

Mean Arterial Pressure

0

10

20

30

40

50

60

70

80

90

T -

15

T -

5

T +

5

T +

15

T +

25

T +

35

T +

45

T +

55

T +

65

T +

75

T +

85

T +

95

T +

105

T +

115

T +

125

T +

135

T +

145

T +

155

T +

165

T +

175

Time (min)

Ave

rag

e M

AP

(m

mH

g)

A

CF

CG

SD

W

ResultsResults

Initial Hemostasis

Incidence of Rebleeding

ResultsResults

ResultsResults

Survival

ObservationsObservations

CELOX-A: May only need 1 injector

Combat Gauze: 4 foot roll takesTime to completely pack

ChitoFlex: Must completely unroll

WoundStat: Over half packed manuallyInto 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

– initial hemostasis over other agents • except CombatGauze

• Chitoflex – incidence of rebleeding

• WoundStat – 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 USNAssistant Investigators: John Devlin, MDSara Kircher, BS Robert Lueken, MDMichael Melia, MD Andrew Johnson, MDVeterinarian: Len Murray, DVMStatistical Analysis: Gregory J Zarow,PhD