Chitosan-based lifefoam improves survival in lethal noncompressible abdominal bleeding in swine

Abstract

BackgroundIn military combat settings, noncompressible closed cavity exsanguination is the leading cause of potentially survivable deaths, with no effective treatment available at point of injury. The aim of this study was to assess whether an expanding foam based on hydrophobically modified chitosan (hm-chitosan) may be used as a locally injectable hemostatic agent for the treatment of noncompressible bleeding in a swine model. MethodsA closed-cavity, grade V hepato-portal injury was created in all animals resulting in massive noncoagulopathic, noncompressible bleeding. Animals received either fluid resuscitation alone (control, n = 8) or fluid resuscitation plus intraperitoneal hm-chitosan agent through an umbilical port (experimental, n = 18). The experiment was terminated at 180 minutes or death (defined as end-tidal CO2 <8mmHg or mean arterial pressure [MAP] <15mmHg), whichever came first. ResultsAll animals had profound hypotension and experienced a near-arrest from hypovolemic shock (mean MAP = 24 mmHg at 10 minutes). Mean survival time was higher than 150 minutes in the experimental arm versus 27 minutes in the control arm (P < .001). Three-hour survival was 72% in the experimental group and 0% in the control group (P = .002). Hm-chitosan stabilized rising lactate, preventing acute lethal acidosis. MAP improved drastically after deployment of the hm-chitosan and was preserved at 60 mmHg throughout the 3 hours. Postmortem examination was performed in all animals and the hepatoportal injuries were anatomically similar. ConclusionIntraperitoneal administration of hm-chitosan-based foam for massive, noncompressible abdominal bleeding improves survival in a lethal, closed-cavity swine model. Chronic safety and toxicity studies are required.