Insulin versus vasopressin and epinephrine to treat beta-blocker toxicity

Clin Toxicol (Phila). 2007 May;45(4):396-401. doi: 10.1080/15563650701285412.

Abstract

Objective: We compared insulin and glucose (IN/G) to vasopressin plus epinephrine (V/E) in a pig model of beta-blocker toxicity. Primary outcome was survival over four hours.

Methods: Ten pigs received a 0.5 mg/kg bolus of propranolol IV followed by a continuous infusion. At the point of toxicity 20 ml/kg normal saline was rapidly infused and the propranolol drip continued at 0.125 mg/kg/min over four hours of resuscitation. Each pig was randomized to either IN/G or V/E. The V/E group began with epinephrine at 10 mcg/kg/min titrated up by 10 mcg/kg/min every 10 min to 50 mcg/kg/min or until baseline was obtained. Simultaneously, these pigs received vasopressin at 0.0028 units/kg/min, titrated upwards every 10 min to 0.014 units/kg/min or until baseline was obtained. The IN/G group began with a 2 units/kg/hr drip and increased by 2 units every 10 minutes to 10 units/kg/hr, or until baseline hemodynamics were obtained. CO, SVR, systolic blood pressure, HR, MAP, glucose, and potassium were monitored. Glucose was given for values <60 mg/dl.

Results: The study was terminated early due to marked survival differences after five pigs were entered in each group. All IN/G group pigs survived four hours. All V/E group pigs died within 90 min. CO in the IN/G group increased throughout the four hours, rising above pre-propranolol levels, while MAP, SBP, and SVR all trended slightly downward. CO in the V/E group dropped until death, while MAP, SBP, and SVR rose precipitously until 30-60 minutes when these dropped abruptly until death. Glucose was required in the IN/G group.

Conclusion: In this swine model, IN/G is superior to V/E to treat beta-blocker toxicity. IN/G has marked inotropic properties while the vasopressor effects of V/E depress CO and contribute to death. Increasing SVR in this condition is detrimental to survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / therapeutic use*
  • Adrenergic beta-Antagonists / poisoning*
  • Animals
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Drug Therapy, Combination
  • Endpoint Determination
  • Epinephrine / therapeutic use*
  • Glucose / therapeutic use
  • Heart Rate / drug effects
  • Hydrogen-Ion Concentration
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Propranolol / poisoning*
  • Survival Analysis
  • Swine
  • Vascular Resistance / drug effects
  • Vasoconstrictor Agents / therapeutic use*
  • Vasopressins / therapeutic use*

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Hypoglycemic Agents
  • Insulin
  • Vasoconstrictor Agents
  • Vasopressins
  • Propranolol
  • Glucose
  • Epinephrine