Insulin versus vasopressin and epinephrine to treat beta-blocker toxicity.
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.


CONCLUSIONS
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.
Holger
Joel S
JS
Regions Hospital Department of Emergency Medicine, St. Paul, Minnesota 55101, USA. Joel.S.Holger@Healthpartners.com
Engebretsen
Kristin M
KM
Fritzlar
Sandy J
SJ
Patten
Lane C
LC
Harris
Carson R
CR
Flottemesch
Thomas J
TJ
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000506:poisoning*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D004837:Epinephrine / Q000627:therapeutic use*; D005947:Glucose / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D011433:Propranolol / Q000506:poisoning*; D016019:Survival Analysis; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D014667:Vasopressins / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007004:Hypoglycemic Agents; D007328:Insulin; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D011433:Propranolol; D005947:Glucose; D004837:Epinephrine