Interactions between nicardipine and enflurane, isoflurane, and sevoflurane

Abstract

Purpose: During nicardipine induced hypotension, different inhalational anaesthetics may have different effects on haemodynamic variables, sympathetic function and drug metabolism. Therefore, the haemodynamic effects and pharmacokinetics of nicardipine were studied in the presence of the three inhalation anaesthetics enflurane, isoflurane and sevoflurane. Methods: Thirty patients scheduled for neurosurgery were randomly assigned to one of three anaesthetic techniques: enflurane, isoflurane or sevoflurane. Nicardipine (0.017 mg · kg-1) was administered during stable anaesthesia and the following measurements made for 30 min: blood pressure, heart rate, and plasma concentration of norepinephrine, epinephrine and nicardipine. Results: With sevoflurane, plasma concentrations of nicardipine, five minutes after administration, (39.8 ± 3.5 ng · ml-1, mean ± SEM) were higher (P < 0.05) than in the other two groups (28.3 ± 2.9 ng · ml-1, 32.6 ± 4.3 ng · ml-1, enflurane and isoflurane, respectively). With isoflurane, the approximated half-life of nicardipine (14 ± 4 min) was shorter and clearance (2.1 ± 0.3 l · min-1) more rapid. Peak heart rates were similar in all groups but elevated rates continued longer with isoflurane (>30 min). Nicardipine-induced reduction in blood pressure was greater with sevoflurane but low pressures persisted for longer with isoflurane. Plasma catecholamine concentrations increased with isoflurane and enflurane, but not with sevoflurane: considerably higher epinephrine concentrations were seen with isoflurane. Conclusion: This study showed that the action of nicardipine is modified by different inhalational anaesthetic agents. Nicardipine has a prolonged duration of action in the presence of isoflurane and produces greater initial hypotension with sevoflurane.