Comparison of hydroxocobalamin with other resuscitative fluids in volume-controlled and uncontrolled hemorrhage models in swine (Sus-scrofa)

Abstract

BACKGROUND Traumatic hemorrhage is the leading cause of preventable death in military environments. Treatment with resuscitative fluids and blood components is based on availability, thus, frequently unavailable in the prehospital setting, due to lack of resources and costs. Hydroxocobalamin (HOC), increases blood pressure via nitric oxide scavenging. We evaluated HOC as a resuscitation fluid, in two swine hemorrhage models. Our objectives were to (1) evaluate whether HOC treatment following hemorrhagic shock improves hemodynamic parameters and (2) determine whether those effects are comparable to whole blood (WB) and lactated ringers (LR). METHODS Yorkshire swine (Sus scrofa) (n = 72) were used in models of controlled hemorrhage (CH) (n = 36) and uncontrolled hemorrhage (UH) (n = 36). Randomized animals received treatment with 500 mL of either WB, LR, HOC (150 mg/kg), followed by a six-hour observation (n = 6 each group). Survival, hemodynamics, blood gases (ABGs) and chemistries were collected. Data reported as mean ± standard error of the mean and statistical analysis by ANOVA (p < 0.05). RESULTS Blood loss for CH was 41% ± 0.02 versus 33% ± 0.07 for UH. For CH, HOC treatment maintained higher systolic blood pressure (sBP, mm Hg) compared with WB and LR (72 ± 1.1; 60 ± 0.8; 58 ± 1.6; respectively). Heart rate (HR), cardiac output (CO), Sp o 2 and vascular resistance were comparable with WB and LR. The ABG values were comparable between HOC and WB. For UH, HOC treatment maintained sBP levels comparable to WB and higher than LR (70 ± 0.9; 73 ± 0.5; 56 ± 1.2). HR, CO, Sp o 2 , and systemic vascular resistance were comparable between HOC and WB. Survival, hemodynamics, blood gases were comparable between HOC and WB. No survival differences were found between cohorts. CONCLUSION Hydroxocobalamin treatment improved hemodynamic parameters and Ca2+ levels compared with LR and equivalent to WB, in both models. Hydroxocobalamin may be a viable alternative when WB is not available.