Page 53 - Journal of Special Operations Medicine - Fall 2014

Celox Gauze for 12 and 24 hours without complica- To date, there is no published study that has compared
tions at a Role 2 medical treatment facilities. 28 the efficacy of Combat Gauze with that of the new chito-
san-based gauzes in a coagulopathic lethal-wound animal
Coagulopathy and Hemorrhage Control model. Preliminary (small sample size) screening tests of
Acute coagulopathy was found to be present in up to two chitosan dressings (Celox Gauze and ChitoGauze)
38% of severely injured combat casualties requiring at USAISR in coagulopathic (hypothermic and hemodi-
massive transfusion on arrival at a Combat Support luted) pigs showed no efficacy when these dressings were
17
Hospital. In the civilian arena, 25% of trauma patients used to stop lethal arterial or mixed soft-tissue bleedings
were coagulopathic on arrival at a Level I trauma cen- (unpublished data, Kheirabadi, 2011). However, as in-
61
ter. Most animal studies have used coagulopathic liver dicated here previously (see “Proximate Cause”), these
injury models for testing hemostatic products. In these preliminary unpublished findings are in contrast to six
13
models, both Combat Gauze and chitosan dressings 21,22 additional published animal studies reporting efficacy of
have been assessed with encouraging results. However, chitosan dressings under coagulopathic conditions. 19–24
this model represents off-label internal application in a One published civilian cardio thoracic surgical case re-
25
high-flow, low-pressure hemorrhage that is not repre- port and two published trauma-induced coagulopathic
37
sentative of lethal extremity hemorrhage. Two studies combat casualties case series also support effectiveness of
have been published using the USAISR standard model chitosan-based dressings in coagulopathic patients. 28,29
in the face of combined dilutional and hypothermic co-
agulopathic conditions. In the first, both Combat Gauze It is important to note that regardless of which method
and WoundStat were compared with a fibrin/thrombin is used in the laboratory to create coagulopathic animal
dressing (FAST). In this model, Combat Gauze con- models, these methods attempt to replicate the pertur-
trolled hemorrhage in only 5 of 15 subjects, whereas bations compared with the actual cascade of metabolic
FAST was successful in 10 of 15. These results, how- disturbances from trauma-induced coagulopathy (TIC)
9
ever, did not reach statistical significance. Additionally, in, for example, combat casualties. In severe trauma (i.e.,
Floyd et al. reported poor efficacy of Combat Gauze in blunt or penetration), resulting massive tissue injury in
a hemodilution coagulopathic swine model (60% blood combination with shock are the central mechanisms of
volume withdrawn and equal colloid fluid replacement) acute traumatic coagulopathy (ATC). This is character-
10
with only 50% animal survival. These contradictory ized by protein C activation resulting in anticoagulation,
results are likely due to differences in the severity and hyperfribinolysis, and fibrinogen depletion. These ini-
62
mechanism of inducing coagulopathy in each study. In tial ATC events lead to worse patient outcomes and in-
the USAISR model, severe coagulopathy is induced by creased mortality. 62–64 Other recognized iatrogenic causes
replacing 50% of pigs’ blood volume with a synthetic of coagulopathy are secondary to ATC, such as intrave-
colloid (Hextend [BioTime Inc.; http://www.biotime nous fluid hemodilution, hypothermia, and acidosis (le-
®
inc.com/hextend/]) and 32°C hypothermia, while other thal triad), which individually and collectively exacerbate
studies either use a systemic heparinization or induce the hypocoagulable state resulting in systemic TIC. 62,65
hypothermia to produce a moderate coagulopathy.
As stated previously, because the interpretation of he-
[Note: As of March 2013, Combat Gauze was approved mostatic efficacy between injury models is challenging,
by the FDA (510(K); #K120782). Combat Gauze has been most weight is now given to hemostatic products tested
tested in clinical trials, and its efficacy has been shown in the USAISR standard model (6mm femoral arteriot-
only in patients treated with the anticoagulation medi- omy). Additionally, one of the continuing assumptions
cations: heparin, clopidrogel bisulfate, and warfarin. No of current animal wound models is that the outcome of
clinical data were presented to the FDA for reported ef- efficacy studies is translatable to human casualties with
ficacy in trauma-induced coagulopathic patients: http:// complex and varying wound geometry. Furthermore,
www.accessdata.fda.gov/cdrh_docs/pdf12/K120782 the application of dressing by first responders who may
.pdf.] have little experience with the product can very well be
different than that by an investigator in the lab, particu-
As previously described, chitosan works independently larly in the context of the prehospital battlefield with
of the coagulation cascade. Given a high incidence of inherent environmental, illumination, and weather ex-
coagulopathy in patients presenting to combat support tremes combined with the effects of an opposing force.
hospitals, the overall efficacy of chitosan-based dress- Other than observational data and limited survey re-
ings to control coagulopathic hemorrhage is an impor- sults, 30–32,66 product effectiveness in the hands of medics
9
tant issue. These two studies by Kheirabadi et al. and has yet to be well documented in the literature to deter-
10
Floyd et al. suggest that Combat Gauze may not be the mine if hemostatic product performance indicators in
dressing of choice for external application in coagulo- the laboratory setting are reflective of their effectiveness
pathic combat casualties. on the battlefield. Nonetheless, to date, these case series

Chitosan-Based Hemostatic Gauze Dressings 45