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Intralipid Prolongs Survival in a Rat Model of Verapamil Toxicity
Author(s) -
Tebbutt Simon,
Harvey Martyn,
Nicholson Tonia,
Cave Grant
Publication year - 2006
Publication title -
academic emergency medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.221
H-Index - 124
eISSN - 1553-2712
pISSN - 1069-6563
DOI - 10.1197/j.aem.2005.08.016
Subject(s) - verapamil , medicine , toxicity , saline , bolus (digestion) , anesthesia , heart rate , pharmacology , calcium channel blocker , calcium , blood pressure
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.