Insulin improves survival in a canine model of acute beta-blocker toxicity.
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 fitted with instruments by means of thoracotomy and vascular cutdown for multiple cardiodynamic, hemodynamic, metabolic, and electrical measures. After basal measurements were taken, animals received intravenous propranolol (.25 mg/kg/minute) continuously for the remainder of the experiment. 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 micrograms/kg bolus, then 150 micrograms/kg/hour infusion), or epinephrine (1 microgram/kg/minute). Animals were monitored until death or for 240 minutes.


RESULTS
Propranolol 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 greater for insulin-treated animals, compared with either glucagon-treated (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.


CONCLUSIONS
Insulin is a superior antidote compared with glucagon or epinephrine in an anesthetized canine model of acute beta-blocker toxicity.
Kerns
W
W
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC, USA.
Schroeder
D
D
Williams
C
C
Tomaszewski
C
C
Raymond
R
R
D000208:Acute Disease; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000506:poisoning*; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D004837:Epinephrine / Q000627:therapeutic use; D005934:Glucagon / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D011041:Poisoning / Q000188:drug therapy; D011433:Propranolol / Q000506:poisoning*; D016019:Survival Analysis
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000931:Antidotes; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon; D011433:Propranolol; D004837:Epinephrine