Addition of an alginate to a modified zeolite improves hemostatic performance in a swine model of lethal groin injury.
BACKGROUND
QuikClot is a zeolite-based hemostatic agent that can control severe hemorrhage through adsorption of water in an exothermic reaction. Ion exchanging the calcium ions in zeolite type 5A with cations of a reduced hydration enthalpy can reduce heat generation, but its effect on the hemostatic efficacy is not clear. We developed a new compound zeolite hemostat and tested it against controls in a modified swine model of battlefield injury.


METHODS
A modified complex groin injury was created in 42 swine (39.4 +/- 2.6 kg). This included semitransection of the proximal thigh (level of inguinal ligament) and semidivision of the femoral artery and vein. After 3 minutes, the animals were assigned to (1) no dressing (ND), (2) standard dressing (SD), (3) SD + zeolite hemostat (QC), (4) SD + chemically modified zeolite hemostat, where calcium was substituted with silver (Ag) and zinc (Zn) simultaneously, (Ag.Zn-zeolite), and (5) SD+ the compound hemostat composed of Ag.Zn-zeolite and alginate. Resuscitation was started 15 minutes after application of dressing (500 mL of 6% hetastarch during 30 minutes). Survival for 180 minutes was the primary endpoint for this study. Blood loss, wound temperatures, and histologic tissue damage were recorded as well. In addition, the antibacterial activities of these hemostatic agents were tested on agar plates. At the end of experiment, the strength of clots was carefully measured by a Tablet Hardness Analyzer.


RESULTS
Mortality in the group treated with the application of the compound hemostat composed of Ag.Zn-zeolite and alginate was 10% versus 100% in the ND group and 71% in the SD group (p < 0.001 vs. ND group, p < 0.05 vs. SD group). The QC group had a mortality rate of 22%, whereas application of Ag- and Zn-substituted zeolite associated with a mortality rate of 37.5%. Ag and Zn substitution of zeolite reduced the in vivo temperature peak to 39.8 degrees C +/- 2.3 degrees C and no thermal injury of tissue was noted in these groups. Ag- and Zn-substituted zeolite posed an antibacterial ability against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Addition of an alginate into the modified zeolite hemostat reinforced the strength of clots to 18.52 N +/- 1.33 N.


CONCLUSIONS
Application of the compound zeolite hemostat can effectively control hemorrhage and dramatically reduce mortality from a lethal groin wound. In addition to its antibacterial properties, Ag- and Zn-substituted zeolite hemostat can decrease the exothermic reaction and greatly attenuate the heat-induced tissue injury.
Li
Jiang
J
Department of Plastics and Burns, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Yan
Wei
W
Jing
Li
L
Xueyong
Li
L
Yuejun
Li
L
Wangzhou
Li
L
Shaozong
Chen
C
D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001431:Bacteriological Techniques; D001458:Bandages; D001760:Bleeding Time; D004195:Disease Models, Animal; D004338:Drug Combinations; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D005263:Femoral Artery / Q000293:injuries*; D005268:Femoral Vein / Q000293:injuries*; D006119:Groin / Q000293:injuries*; D006470:Hemorrhage / Q000188:drug therapy*; D006490:Hemostatics / Q000008:administration & dosage*; D008297:Male; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000188:drug therapy; D012834:Silver / Q000008:administration & dosage*; D013211:Staphylococcus aureus / Q000187:drug effects; D013530:Surgical Wound Infection / Q000517:prevention & control; D013552:Swine; D014945:Wound Healing / Q000187:drug effects; D017641:Zeolites / Q000008:administration & dosage*; D015032:Zinc / Q000008:administration & dosage*
D000464:Alginates; D004338:Drug Combinations; D006490:Hemostatics; D017641:Zeolites; D012834:Silver; D015032:Zinc