Hemodynamic effects of intravenous fat emulsion in an animal model of severe verapamil toxicity resuscitated with atropine, calcium, and saline

Background: Intravenous fat emulsion (IFE) decreases cardiotoxicity from several lipid-soluble drugs, including verapamil. Objectives: To verify if the addition of IFE to the standard treatment of severe verapamil toxicity would improve hemodynamics and survival. Methods: Fourteen dogs were instrumented to measure systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate, cardiac output, central venous pressures, left ventricular pressure changes over time, mixed venous oxygen saturation, pH, and base excess. Verapamil toxicity, defined as a 50% decrease in MAP, was induced with verapamil at 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil infusion rate. Following verapamil toxicity, the verapamil infusion rate was changed to 2 mg/kg/hr and continued for 90 minutes. All dogs were resuscitated with atropine (0.04 mg/kg intravenously) and calcium chloride (15 mg/kg intravenously every 5 minutes for three doses) and then randomized to receive either IFE (7 mg/kg of 20%) intravenously or equivalent volumes of 0.9% normal saline over 30 minutes. Measurements were recorded for 120 minutes by investigators blinded to the treatment. Data were analyzed using analysis of variance, survival analysis, and log-rank test. Results: Before the 30-minute IFE or normal saline infusion, there were no differences in hemodynamic parameters. After IFE or normal saline infusion, the IFE-treated group had higher MAP at 30 minutes (95% confidence interval [CI] = 5.6 to 44.7 mm Hg), 45 minutes (95% Cl = 10.8 to 50.0 mm Hg), and 60 minutes (95% CI = 10.2 to 53.1 mm Hg). Kaplan-Meier 120-minute survival rate was 14% (95% Cl = 0.5% to 53%) for the saline group as compared with 100% (95% Cl = 59% to 100%) for the IFE group (p = 0.01). Conclusions: Standard resuscitation and IFE increase MAP and survival in an animal model of severe verapamil toxicity compared with standard resuscitation alone.