Phenytoin-induced hypotension in animals receiving sympathomimetic pressor support

The observation that intravenous phenytoin infusion in patients receiving dopamine hydrochloride causes pronounced hypotension stimulated a series of animal studies to investigate the mechanism of phenytoin-dopamine interaction and to determine if phenytoin can be used safely with other pressors. Intravenous phenytoin was administered at 25 or 50 mg/min to normotensive dogs and dogs rendered hypotensive by hemorrhage, coronary artery ligation, or endotoxin. Phenytoin infusion was superimposed on infusions of dopamine, norepinephrine, phenylephrine, or isoproterenol. Phenytoin infusion in hypotensive dogs on pressor support caused a significant decrease in systemic vascular resistance (P < 0.0001) and a substantial decrease in mean arterial pressure. Dogs supported by phenylephrine had the smallest observed change in mean arterial pressure. The decrease in systemic vascular resistance appears to be secondary to phenytoin induced peripheral vasodilation. It is concluded that when phenytoin infusion is required in the critically ill patient, it should be administered very slowly and with continuous monitoring. When pressor support is required concomitantly with phenytoin infusion, a pure a agonist may minimize the risk of an adverse reaction.