Alfentanil Pharmacokinetics in Cardiac Surgical Patients

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Abstract

There is growing interest in early tracheal extubation and intensive care unit (ICU) discharge of cardiac surgical patients. Among the opioids currently available, alfentanil seems to be particularly suited to these goals because of its pharmacokinetic and pharmacodynamic characteristics. However, the pharmacokinetics of alfentanil after cardiopulmonary bypass (CPB) have not been fully characterized. Eight patients undergoing coronary artery bypass grafting (CABG) with hypothermic CPB received alfentanil 125 μg/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 proteins (n = 3). Arterial blood samples were obtained from another six patients for measurements of the concentrations of plasma proteins at various stages of the perioperative period. Compared to the pre-CPB period as well as to patients not exposed to CPB, CABG patients after CPB exhibited an increased elimination half-time (t1/2β - 180 ± 55 min sd), central distribution volume (Vc = 0.25 ± 0.07 L/kg), and total volume of distribution (Vdss 0.63 ± 0.08 L/kg; Vd area 0.92 ± 0.23 L/kg) which reflected a 33%-50% decrease in α1acid glycoprotein, the principal plasma protein to which alfentanil is bound. There was no substantial change in the concentration of free alfentanil at the start of CPB. The clearance of total alfentanil was not affected 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 alfentanil concentration in plasma and the central nervous system (CNS), and presumably a stable level of alfentanil effect. 3) If alfentanil therapy is initiated after CPB, the loading dose should not be altered substantially. 4) The decline of alfentanil concentrations from a steady state level in plasma will be prolonged by as much as 25%-100% after CPB.

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