Purpose: To compare rescue with high dose insulin (HDI) alone versus HDI plus an alpha-adrenergic agent in treatment of overdose due to a dihydropyridine calcium channel blocker. Given the vasodilating properties of the dihydropyridines, our hypothesis was that the addition of an alpha-adrenergic agent would improve survival, cardiac index (CI), mean arterial pressure (MAP), and systemic vascular resistance (SVR).
Methods: There were three arms with five pigs in each of the following: control (C), insulin/glucose (IN) only, and phenylephrine plus insulin (PE/IN). Pigs were anesthetized with isoflourane and nitrous oxide, underwent tracheostomy, placement of a Swan-Ganz catheter and an arterial line. All pigs received a nifedipine (N) infusion of 0.0125mcg/kg/min until a point of toxicity was reached, defined as a 25% decrease in the baseline product of MAP x cardiac output. A 20ml/kg bolus of saline (NS) was infused over 10 minutes and the N infusion continued over a 4-hour resuscitation phase, with NS at 2 ml/kg/hr. The C arm received NS only. The IN arm received an insulin infusion begun at 2 units/kg/hr and increased q10 minutes by 2 units to a maximum of 10 units/kg/hr. The PE/IN arm was given a PE infusion at 2.4 mcg/kg/min titrated to 3.6 mcg/kg/min after full titration of IN. The above parameters were recorded. Results: No baseline differences among the groups, including time to toxicity, were found. One pig survived in the C arm, four in the IN arm and 5 in the IN/PE arm (p = .32 for IN/PE to IN). When comparing IN (n = 5) to the PE/IN (n = 5) arms by two-tailed t-test at the conclusion of the resuscitation no differences were found for CI (p = .05), SVR (p = .34), heart rate (p = .95), MAP (p = .99), PVR (p =.07) or base excess (p = .36).
Conclusion: Survival was not different between the IN and IN/PE arms. No differences were found for cardiovascular parameters at the end of the resuscitation. Implications for Translation into Practice: The addition of phenylephrine to high-dose insulin does not improve the treatment of toxicity due to dihydropyridine calcium-channel blockers.