ALFENTANIL PHARMACOKINETICS IN CARDIAC SURGICAL PATIENTS

There is growing interest in early tracheal extubation and intensive c are unit (ICU) discharge of cardiac surgical patients. Among the opioi ds currently available, alfentanil seems to be particularly suited to these goals because of its pharmacokinetic and pharmacodynamic charact eristics. However, the pharmacokinetics of alfentanil after cardiopulm onary bypass (CPB) have not been fully characterized. Eight patients u ndergoing coronary artery bypass grafting (CABG) with hypothermic CPB received alfentanil 125 mu g/kg intravenously (IV) at the induction of anesthesia and again 5 h later after the completion of CPB. Arterial blood samples were analyzed for alfentanil (n = 8) and for plasma prot eins (n = 3). Arterial blood samples were obtained from another six pa tients for measurements of the concentrations of plasma proteins at va rious stages of the perioperative period. Compared to the pre-CPB peri od as well as to patients not exposed to CPB, CABG patients after CPB exhibited an increased elimination half-time (t(1/2 beta) = 180 +/- 55 min so), central distribution volume (V-c = 0.25 +/- 0.07 L/kg), and total volume of distrbution (V-d(ss) 0.63 +/- 0.08 L/kg; V-d area 0.92 +/- 0.23 L/kg) which reflected a 33%-50% decrease in alpha(1)-acid gl ycoprotein, the principal plasma protein to which alfentanil is bound. There was no substantial change in the concentration of free alfentan il at the start of CPB. The clearance of total alfentanil was not affe cted significantly by CPB. We conclude: 1) Alfentanil pharmacokinetics in CABG patients before CPB are similar to those found in noncardiac surgical patients and volunteers. 2) Alfentanil infusion rates should be reduced during and after CPB to maintain a stable level of free alf entanil concentration in plasma and the central nervous system (CNS), and presumably a stable level of alfentanil effect. 3) If alfentanil t herapy is initiated after CPB, the loading dose should not be altered substantially. 4) The decline of alfentanil concentrations from a stea dy state level in plasma will be prolonged by as much as 25%-100% afte r CPB.