Midazolam and fentanyl continuous infusion anesthesia for cardiac surgery: comparison of computer-assisted versus manual infusion systems

Abstract

Continuous infusion of intravenous anesthetics can be achieved either by a manually controlled infusion (MCI) pump, or by a computer-assisted continuous infusion (CACI) pharmacokinetic model-driven infusion system. Randomized double-blind comparisons of the two infusion systems for general anesthesia were performed in 24 patients undergoing coronary artery bypass grafting. Patients were allocated to receive continuous infusions of midazolam and fentanyl by either a MCI device or CACI. Midazolam and fentanyl infusions were independently titrated to maintain hemodynamic stability, defined as mean arterial pressure (MAP) and heart rate (HR) within 20% of baseline values. As directed by the study design, comparable hemodynamic control was achieved in both groups. Mean plasma fentanyl concentrations measured at specific timepoints were similar between groups. The plasma midazolam level for induction was 196 ± 139 ng/mL in the CACI group and 300 ± 128 ng/mL in the MCI group, and the fentanyl level was similar in both groups, 6.7 ± 1.9 ng/mL in CACI and 6.3 ± 4.6 ng/mL in the MCI group. The drug levels were lower ( P < 0.05) for midazolam during maintenance of anesthesia and similar for fentanyl during the maintenance of anesthesia. In the MCI group, the average duration of anesthesia was 246.5 ± 35.0 minutes, with a mean total fentanyl dose of 30.27 ± 11.14 μg/kg. In the CACI group, the average duration of anesthesia was 230.8 ± 44.1 minutes, with a mean total fentanyl dose of 34.61 ± 5.40 μg/kg ( P > 0.05 for comparisons between groups for duration of anesthesia and total fentanyl dose). Mean plasma midazolam concentrations measured at specific timepoints, and total amount of midazolam delivered per case, were significantly lower with CACI (mean total midazolam dose: CACI = 191.85 ± 49.51 μg/kg, MCI = 267.79 ± 84.22 μg/kg; P < 0.05). Furthermore, variability in plasma fentanyl and midazolam concentrations was significantly greater in the group receiving manually controlled infusions. It is concluded that CACI and MCI provided excellent hemodynamic stability with opioid drug concentrations lower than techniques based on fentanyl alone. The CACI method achieved more precise plasma concentrations, but both methods of drug delivery produced relatively similar plasma concentrations despite the very different dosing concepts.