Efficacy of Treating Nifedipine-Induced Shock with Hydroxocobalamin in a Swine Model.

Abstract

Introduction: Calcium channel antagonists contribute to many overdose related deaths each year and treatment options are limited. Hydroxocobalamin has shown promise in reversal of multiple shock states, and we evaluated its use in the treatment of nifedipine-induced shock in a swine model.

Methods: Twenty-two swine (39 to 50 kg) were anesthetized, instrumented, and acclimatized. Toxicity was induced by administering a nifedipine infusion at 0.0266 mg/kg/min. Once the toxic end point, defined as a 20% decrease from the initial mean arterial pressure, was reached, all animals received a 20 mL/kg bolus of saline and either 60 mL of saline (NP group) or 150 mg/kg of hydroxocobalamin dissolved in 60 mL of saline (NP + HX group). Hemodynamics were analyzed and compared between the NP and NP + HX groups over time using linear mixed models with Bonferroni correction.

Results: Modeling of the hemodynamic data demonstrated an increase in both systolic blood pressure and change in MAP from the nadir. Mean arterial pressure (MAP) and diastolic blood pressure were increased (p < 0.01) in the NP + HX group at multiple time points. There were no differences detected in the time-to-death between groups.

Conclusion: Improvements in hemodynamics were noted in the group treated with hydroxocobalamin, but there was no evidence for improvement in mortality. Given this, hydroxocobalamin may serve a role in bridging patients to high dose insulin, vasopressors, extracorporeal membrane oxygenation, or transfer to a higher level of care.