Effect of cardiopulmonary bypass on fentanyl distribution and elimination

Clinical Pharmacology and Therapeutics
A J KoskaW G Kramer

Abstract

Fentanyl kinetics was studied in two groups of six patients, one group undergoing surgery with and one without cardiopulmonary bypass; the latter served as the controls. Plasma fentanyl concentrations declined biexponentially in the control patients with an average half-life (t1/2 beta) of 3.3 +/- 1.1 hr, total plasma clearance of 11.2 +/- 3.4 ml/min/kg, and volume of distribution (Vd beta) of 3.2 +/- 1.5 l/kg. The plasma concentration/time curves were severely disrupted during cardiopulmonary bypass but appeared to regain a log-linear decay once bypass was complete. This elimination phase had a t1/2 of 5.2 +/- 2.7 hr, longer than that in the control patients. Since fentanyl is eliminated primarily by hepatic metabolism, decreased liver plasma flow observed during and after bypass, as evidenced by a 30% decrease in indocyanine green clearance, may contribute to the extended t1/2. The prolonged t1/2 had clinical importance because of potentially prolonged effects and their relation to other drugs and the clinical management of the patient.

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