INSULIN IMPROVES SURVIVAL IN A CANINE MODEL OF ACUTE BETA-BLOCKER TOXICITY

Study objective: To compare the efficacy of a novel antidote, insulin, with standard treatments, glucagon and epinephrine, in a canine model of acute beta-blocker toxicity. Methods: Anesthetized dogs were fitte d with instruments by means of thoracotomy and vascular cutdown for mu ltiple cardiodynamic, hemodynamic, metabolic, and electrical measures. After basal measurements were taken, animals received intravenous pro pranolol (.25 mg/kg/minute) continuously for the remainder of the expe riment. Toxicity was defined as a 25% decrease in the product of heart rate times mean blood pressure. Thirty minutes after the development of toxicity, toxic measures were taken (treatment 0 minutes), and then the animals (n=6 each group) received either sham (saline solution), insulin (4 IU/minute with glucose clamped), glucagon (50 mu g/kg bolus , then 150 mu g/kg/hour infusion), or epinephrine (1 mu g/kg/minute). Animals were monitored until death or for 240 minutes. Results: Propra nolol decreased contractility, left ventricular pressure, and systemic blood pressure, and resulted in death of all sham-treated animals by 150 minutes. Six of six insulin-treated, four of six glucagon-treated, and one of six epinephrine-treated animals survived. Survival was gre ater for insulin-treated animals, compared with either glucagon-treate d (P<.05) or epinephrine-treated animals (P<.02) by the log-rank test. Insulin-treated animals were characterized by improved cardiodynamics and hemodynamics, increased myocardial glucose uptake, and decreased serum potassium. Conclusion: Insulin is a superior antidote compared w ith glucagon or epinephrine in an anesthetized canine model of acute b eta-blocker toxicity.