Fentanyl clearance and volume of distribution are increased in patients with major burns

This study examined the pharmacokinetics of fentanyl in burned patients during the hyperdynamic phase. Twenty adults, aged 37 +/- 2 years (mean SE), with 49 +/- 3% total body surface area burn, were studied at 17 +/- 2 days after the injury and compared to demographically matched controls. After a 200-mu g IV bolus of fentanyl, blood samples (n = 20) were collected for 4.5 hours. Concentration-time curves were fitted to a 2-compartment model. Burned patients had a higher cardiac index. Median fentanyl clearance (CL, 21.0 vs 29.4 mL/kg/min), central comportment volume (V-1, 0.37 vs 0.61 L/kg), and total volume of distribution (V-area, 3.6 vs 5.8 L/kg) were higher in burned patients. Cardiac index was unrelated to CL. The increased V-1 and V-area are likely due to large intravenous fluid replacement and tissue edema. Higher CL and larger V-1 and V-area leading to a lower fentanyl plasma concentration may partially explain the increased opiate requirement previously observed after burn injury.