Drug interactions with sufentanil: Hemodynamic effects of premedication and muscle relaxants

Abstract

Induction of anesthesia with synthetic opioids is occasionally accompanied by undesirable hemodynamic changes such as tachycardia and hypertension, or bradycardia and hypotension. We hypothesized that drug interactions cause many of these adverse responses. Therefore, we conducted a randomized double- blind study to investigate the interactive effect of premedication and muscle relaxants on the hemodynamic response to induction with intravenous (iv) sufentanil 10 μg · kg-1. Eighty patients with left ventricular ejection fraction ≥ 0.40, undergoing elective coronary artery surgery, were premedicated with either morphine 0.1 mg · kg-1 and scopolamine 6 μg · kg-1 intramuscularly, or lorazepam 60 μg · kg-1 orally, and paralyzed with either pancuronium 0.1 mg · kg-1 or vecuronium 0.1 mg · kg-1 iv. The four treatment groups were SP (morphine-scopolamine + pancuronium), LP (lorazepam + pancuronium), SV (morphine-scopolamine + vecuronium), and LV (lorazepam + vecuronium). Hemodynamics were recorded at three time periods: 1) control, 2) induction, and 3) intubation. Premedication-relaxant interactions significantly affected hemodynamics. In group SP, mean heart rate (HR) increased significantly on induction (56 ± 11 to 69 ± 13 beats · min-1), while mean arterial pressure (MAP) and cardiac index (CI) were unchanged. HR, MAP, and CI were significantly higher after induction in group SP compared to the other three groups. In group LP, mean HR increased less than in group SP (56 ± 8 to 62 ± 14 beats · min-1), whereas MAP and CI declined significantly. In group SV, HR and CI were unchanged, but MAP declined significantly. In group LV, HR was stable, whereas both MAP and CI declined significantly. The incidence of pharmacologic interventions during the study period also differed significantly among groups. Intravenous β- adrenergic blocking agents were administered to 6 of 20 patients in group SP, 3 of 20 in group LP, 1 of 20 in group SV, and 0 of 20 in group LV (P = 0.02). Intervention with an iv β-adrenergic blocking agent, iv nitroglycerin, or a volatile anesthetic was required in 9 of 20 patients in group SP, 5 of 20 in group LP, 1 of 20 in group SV, and 2 of 20 in group LV (P = 0.009). Two patients, both in group SP, developed new ischemic ST-segment depression of ≥ 0.1 mV. Preoperative use of β-adrenergic blocking agents exerted a significant effect on hemodynamics. Mean HR was 6-7 beats · min-1 lower throughout the study in patients who were taking β-adrenergic blocking agents preoperatively (n = 49) compared to those who were not (n = 31) (P = 0.005). Drug interactions exert a significant and predictable effect on the hemodynamic response to induction of anesthesia with sufentanil. Careful consideration of potential drug interactions should decrease the incidence of undesirable hemodynamic responses to induction with opioids.