Preprogrammed Infusion of Alfentanil to Constant Arterial Plasma Concentration

A variable rate infusion regimen, designed to rapidly achieve and maintain a target arterial concentration (CT) of 100 μg·L−1 of alfentanil, was developed using the method of Plasma Drug Efflux. This method uses a series of clearance values (Ep), calculated as the ratio of instantaneous infusion rate/arterial plasma drug concentration normalized to lean body mass (LBM), at various sampling times during a suboptimal infusion regimen. Values of Ep are used to calculate an infusion rate versus time profile to achieve CT, and the process is repeated in consecutive small groups of subjects to yield an optimal result, i.e., it is an iterative process. Thirty-three adult surgical patients were given alfentanil during anesthesia for approximately 1 h before cardiopulmonary bypass. In an initial group of four patients, who received a simple two-stage infusion, plasma alfentanil concentration was measured at frequent intervals and Ep(L·min−1·kg LBM−1) was estimated at each sampling time. The calculated infusion rate-versus-time profile to produce CT was obtained from the product Ep × CT for each time point and was transferred to the read-only memory of a computerized infusion pump. This new variable infusion profile was used in four patients, and the process was repeated in three further groups of 5, 8, and 12 patients using in fusion profiles calculated from the previous group. Each set of concentration data was assessed by calculating the performance error (PE), the median performance error (MDPE), i.e., bias, and the median absolute value of PE (MDAPE), i.e., inaccuracy. In the first group, bias and inaccuracy were 17% and 33%, respectively, but the iterative process reduced these to 3% and 10%, respectively, in the fifth group. This compares very favorably with results achieved in previous studies using conventional compartmental model-based pharmacokinetic techniques. The efflux method makes no assumptions about a model, linearity of plasma concentration with dose, or time invariance. It uses data generated only during the infusion and is not subject to the uncertainties of curve fitting. We conclude that the efflux method, combined with dosing based on calculated lean body mass, can be used readily and reliably to develop optimum infusion regimens for alfentanil.