FENTANYL PHARMACOKINETICS IN PATIENTS UNDERGOING RENAL-TRANSPLANTATION

Study Objective. To describe the pharmacokinetics of fentanyl in patie nts undergoing renal transplantation. Design. Prospective. Setting. A large university teaching hospital. Patients. Eight patients (mean +/- SD age 35.5 +/- 11.5 yrs, weight 73.4 +/- 24.8 kg) with end-stage ren al failure receiving kidneys from a living relative; three patients we re never dialyzed, three were receiving peritoneal dialysis, and two w ere receiving hemodialysis. Interventions. Plasma was sampled before a nd at intervals up to 8 hours after intravenous injection of fentanyl 25 mu g/kg before skin incision. Measurements and Main Results. Mean /- SD (range) preoperative values were blood urea nitrogen (BUN) 66 +/ - 30 (35-111) mg/dl; albumin 3.6 +/- 0.7 (2.6-4.5) g/dl; and triglycer ides 414 +/- 352 (156-1270) mg/dl. Elimination half-life was 382 +/- 2 05 minutes; volume of distribution for the central compartment 0.74 +/ - 0.48 L/kg; volume of distribution at steady state (Vd(ss)) 3.1 +/- 2 .0 L/kg; total body clearance 7.5 +/- 5.1 ml.kg(-1).min(-1). A signifi cant inverse relationship between degree of azotemia and fentanyl clea rance was found. The two patients with the highest preoperative BUNs h ad the lowest multiple of clearance and Vd(ss), and were also the only ones to require postoperative mechanical ventilation. Conclusion. Alt hough all patients received a kidney that; functioned well after revas cularization, the large intersubject variability in fentanyl kinetics may, in part, reflect their heterogeneity in dialysis status and renal failure-induced abnormalities. Marked decreases in fentanyl clearance do occur in these patients, appear to be related to very high BUN con centrations, and can lead to prolonged postoperative ventilatory depre ssion.