lanny littlejohn, md lcdr mc (fs/dmo) usn nmcp dept of emergency medicine medical director, tccc...
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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