Bayesian Forecasting Improves the Prediction of Intraoperative Plasma Concentrations of Alfentanil

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Abstract
To achieve therapeutic plasma concentrations of the opioid alfentanil, one must administer the drug as a variable rate continuous infusion. For most patients, using population pharmacokinetic parameters of alfentanil for dosing regimen allows accurate prediction of the plasma concentration of the drug over time. However, for some patients, using such parameters results in systematic over- or underprediction of the concentration. Retrospectively studying a data set (dosage history and measured concentrations) for 34 patients, the authors examined how Bayesian forecasting could improve the precision of prediction. For each patient, a Bayesian regression was performed to estimate "individualized" pharmacokinetic parameters, using population pharmacokinetic values for alfentanil and the measurement of alfentanil in one or more plasma samples from each patient. These individualized parameters were then used to predict the subsequent plasma concentrations of alfentanil over time. By comparing the value of each measured point with its corresponding predicted value, the authors calculated the prediction error as a percentage of the measured value. The precision of the prediction was assessed by the percent mean absolute prediction error. After Bayesian forecasting using a single point sampled at 80 min after start of anesthesia, the average precision of the prediction was 13.8 .+-. 6.1% (SD). Using no Bayesian forecasting and only population values of the pharmacokinetic parameters for the prediction of the concentration, the precision was 24.3 .+-. 16.9%. The improvement in precision brought by Bayesian forecasting was especially noticeable for those patients whose prediction of alfentanil was poor using population pharmacokinetic values (i.e., "outlier" patients). These results suggest that Bayesian forecasting may facilitate optimal administration of alfentanil during long procedures and that a rapid assay should be developed to measure plasma concentrations of alfentanil intraoperatively.