Intralipid Prolongs Survival in a Rat Model of Verapamil Toxicity

Objectives: Verapamil is a lipid-soluble calcium channel blocker with significant mortality in overdose. Previous investigators have demonstrated the benefit of lipid emulsion therapy in ameliorating toxicity from lipid-soluble agents. The authors investigated the effect of Intralipid treatment in a rat model of verapamil toxicity. Methods: Thirty sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, animals were treated with a bolus of either 12.4 mL/kg 20% Intralipid or 12.4 mL/kg 0.9% saline. Verapamil infusion was continued until the animals were killed. Respiratory rate, heart rate, and electrocardiography were sampled every 2.5 minutes throughout. Results: Survival was prolonged in the Intralipid-treated group (44 ± 21 vs. 24 ± 9 minutes; p = 0.003). The median lethal dose was increased in the Intralipid group (25.7 mg/kg [95% confidence interval {CI} = 24.7 to 26.7] vs. 13.6 mg/kg [95% CI = 12.2 to 15.0]). A less marked decrease in heart rate was observed during verapamil infusion in the Intralipid-treated group (6.8 beats/min [95% CI = 8.3 to 5.2] for Intralipid vs. 10.7 beats/min [95% CI = 12.6 to 8.9] for saline; p = 0.001). Conclusions: Intralipid treatment prolongs survival and doubles median lethal dose in a rat model of verapamil toxicity. The mechanism of action remains to be elucidated.