Development of a real-time algorithm for predicting sufentanil plasma levels during cardiopulmonary-bypass surgery, using a systems approach

During cardiopulmonary-bypass (CB) procedures, anesthesiologists have traditionally based the administration of narcotics on general dosage recommendations and past experience. Initial doses are usually based on body weight and supplemental amounts are given in anticipation of, or in response to, the effects of surgical stimuli. There has been considerable recent interest in using the population pharmacokinetics of narcotics to optimize the attainment and maintenance of drug plasma concentrations at analgesic target levels which will blunt the hemodynamic responses to noxious stimuli. Moreover, the undershooting or overshooting of the target can be reduced by application of these principles making drug administration more effective and safer. The present study concerns the development of a model for the computer-guided administration of sufentanil throughout surgical procedures involving CB; there is a paucity of studies which have attempted to model the pharmacokinetics of drugs during CB because of the lack of information on the effects of bypass conditions on the pharmacokinetic parameters. We have attempted to approach the effects of hypothermia on sufentanil clearance by applying a continuous temperature correction to the ultimate elimination rate constant (the terminal eigenvalue). This correction is based primarily on the anticipated effects of temperature on the enzyme-catalyzed reactions which are essential for the elimination of drug from the body. An algorithm for the application of the model is also presented.