Fentanyl pharmacokinetics in patients undergoing renal transplantation

Study Objective. To describe the pharmacokinetics of fentanyl in patients 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 renal failure receiving kidneys from a living relative; three patients were never dialyzed, three were receiving peritoneal dialysis, and two were receiving hemodialysis. Interventions. Plasma was sampled before and at intervals up to 8 hours after intravenous injection of fentanyl 25 μg/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 triglycerides 414 ± 352 (156-1270) mg/dl. Elimination half-life was 382 ± 205 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 significant inverse relationship between degree of azotemia and fentanyl clearance was found. The two patients with the highest preoperative BUNs had the lowest multiple of clearance and Vd(ss), and were also the only ones to require postoperative mechanical ventilation. Conclusion. Although all patients received a kidney that functioned well after revascularization, 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 concentrations, and can lead to prolonged postoperative ventilatory depression.