Insulin versus vasopressin and epinephrine to treat β-blocker toxicity

Abstract

Objective. We compared insulin and glucose (IN/G) to vasopressin plus epinephrine (V/E) in a pig model of β-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 β-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.

Keywords :

• β-blockers
• Overdose
• Poisoning
• Insulin
• Vasopressin
• Epinephrine
• Cardiovascular toxicity

Notes

This research was presented in an abstract and oral presentation form at the North American Congress of Clinical Toxicology, September 9–14, 2005, in Orlando, Florida, USA.

This research was funded in part by a Research Award from the American Academy of Clinical Toxicology, 2004.