Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine.
The cardiovascular and neuromuscular interactions of verapamil and dantrolene were evaluated in 20 chloralose-anesthetized swine. The animals were randomly divided into three groups. Group I, ten animals, received a bolus intravenous injection of 0.1 mg . kg-1 of verapamil followed by the continuous infusion of 5 micrograms . kg-1 . min-1. This group was then randomly divided into two equal subgroups. Five of these animals, Group Ia, continued to receive the verapamil infusion alone. The other five animals, Group Ib, received dantrolene in incremental doses of 1.0, 3.3, and 5.6 mg . kg-1 while the verapamil infusion was continued. An additional group of five animals, Group II, received the same incremental doses of dantrolene but did not receive verapamil. Five control animals, Group III, received the alpha-chloralose anesthetic without dantrolene or verapamil. Neuromuscular function, as measured by twitch height, was affected only by dantrolene, which produced a dose-dependent depression. Verapamil resulted in initial decreases in heart rate, arterial blood pressure, cardiac output, left ventricular dP/dt, and an increase in PR interval. Dantrolene alone produced a mild increase in arterial blood pressure. Dantrolene administration to verapamil-pretreated animals resulted in a profound depression in cardiac function, marked elevation in serum K+ (8.0 +/- 0.7 mEq . l-1), and no change in arterial pH (7.39 +/- 0.02). Cardiac arrest preceded by complete atrioventricular heart block occurred in one animal before and in four animals after the final dantrolene dose was given to animals pretreated with verapamil. Although we cannot extrapolate data from our porcine model to humans, further studies are indicated to help evaluate a possible fatal drug interaction before verapamil and dantrolene are used concomitantly in a clinical setting.
D000818:Animals; D003620:Dantrolene / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004558:Electric Stimulation; D006323:Heart Arrest / Q000139:chemically induced*; D006439:Hemodynamics / Q000187:drug effects*; D006947:Hyperkalemia / Q000139:chemically induced*; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D009469:Neuromuscular Junction / Q000187:drug effects*; D011897:Random Allocation; D013552:Swine; D014700:Verapamil / Q000009:adverse effects*
D014700:Verapamil; D003620:Dantrolene