Incidence of Intra-abdominal Adhesions Following Intraperitoneal Injection of Hemostatic Products in Rabbits

Definitive management of non-compressible intra-abdominal hemorrhage (NCIAH) currently requires a surgeon and operating room capable of performing damage control surgery. In a wartime scenario or a geographically remote environment, these may not be readily available. In this study, we sought to test the safety of 2 emerging injectable hemostatic agents (CounterFlow and Fast Onset Abdominal Management, or FOAM, poloxamer component) versus normal saline control over a prolonged monitoring duration following administration by a non-surgical provider.

The Institutional Animal Care and Use Committee approved all research conducted in this study. We randomized male New Zealand white rabbits into 2 monitoring cohorts of 24 hours and 2 weeks. Each cohort contained 3 treatment groups (n = 4 rabbits/group): CounterFlow, the testable poloxamer component of FOAM, and normal saline control. We injected each treatment intraperitoneally in the left lower abdominal quadrant. Doses were 15 mL/kg for CounterFlow, 6.3 mL/kg for the poloxamer component of FOAM, and 15 mL/kg for normal saline. We conducted all injections under isoflurane anesthesia monitored by trained veterinary staff. Animals were euthanized at each cohort end point, and a veterinary pathologist blinded to treatment type performed necropsy. The primary outcome was incidence of intra-abdominal adhesions at necropsy. Quantitatively, adhesions when present were graded by the veterinary pathologist on a 1 to 4 scale, where "1" represented adhesions involving from 1 to 25% of the examined abdomen, "2" represented from 26 to 50%, "3" represented from 51 to 75%, and "4" represented from 76 to 100%. Qualitatively, adhesions present were graded by degree ("1" = minimal, "2" = mild, "3" = moderate, and "4" = severe) and chronicity ("1" = acute, "2" = subacute, and "3" = chronic). We also drew d-dimer blood values and measured body weights for each animal. Statistical analysis included either repeated measures 2-way ANOVA or a mixed-effects model (in the case of missing data) with Geisser-Greenhouse correction. We adjusted multiple comparisons using Tukey statistical hypothesis tests.

In the 2-week cohort, 3 CounterFlow animals showed adhesions judged to be "1" quantitatively. Qualitatively, 2 of these were assessed as "1" for degree of adhesions and the other demonstrated a "2." On the chronicity of adhesions scale, 1 animal demonstrated a "2" and 2 demonstrated a "3." No animals in other groups (FOAM and control) demonstrated adhesions. CounterFlow-treated animals showed a statistically significant rise in d-dimer values in the 24-hour cohort only. In the 2-week cohort, CounterFlow-treated animals showed a decrease in body weight at 24 hours after injection but returned to their baseline (normal) body weights at 7 days.

Findings from this study demonstrate that the tested ingredients of FOAM poloxamer component are safe for intraperitoneal injection and hold potential for further study directed toward prehospital non-compressible intra-abdominal hemorrhage management by non-surgical providers. Although CounterFlow produced abdominal adhesions in 3 of 4 rabbits in the 2-week cohort, these were determined to be "minimal" or "mild" in degree.