Lung Injury Induced by Major Burns does not Affect Fentanyl Clearance

Han, Tae Hyung; Kim, Ju Hyun; Oh, Kwon Ik; Lee, Jung Hoon; Lee, Jung Wook; Woo, Chul Ho; Kwak, In Suk; Kim, Kwang Min

Abstract

BACKGROUND: Major burns can alter the pharmacokinetics of opiate analgesics, which are commonly used perioperatively. Fentanyl undergoes a significant amount of pulmonary pharmacokinetic transition. This study was conducted to compare the pharmacokinetics of fentanyl in major burns, with and without lung injury, during the subacute hyperdynamic phase of recovery.
METHODS
Twelve adults, with total body surface area (TBSA) 51.0 +/- 11.8% burns, aged 34.9 +/- 9.6 years, with a lung injury related to the burn, were studied at 15.4 +/- 9.4 days after the injury. Another 8 patients, aged 39.8 +/- 10.5 years, with TBSA 46.3 +/- 19.4%, at 19.3 +/- 10.9 days, without lung injury, served as controls. Fentanyl 200microgram was given intravenously over 10 seconds. Blood samples (n = 20) were collected at predetermined intervals. A two-compartment model was used for pharmacokinetic analyses of the fentanyl concentrations, as determined by LC/MS. The cardiac index (CI) was also measured using an esophageal Doppler monitor.
RESULTS
There were no differences in the patient characteristics between the two groups. Those with burns had a significantly higher cardiac index (4.1 +/- 2.4 L/min/m2), clearance (Cl), central (V1) and total volume of distribution (Vd), but there were no differences between those with and without lung injury (30.2 +/- 14.3 vs. 30.1 +/- 5.8 ml/min/kg, 0.8 +/- 0.3 vs. 0.6 +/- 0.2 L/kg, 5.8 +/- 1.7 vs. 5.2 +/- 2.1 L/kg, respectively). Prolonged distribution (t1/2alpha) and elimination half-lives (t1/2beta) were noted in those with burns, but there were no differences between the two groups (3.2 +/- 1.3 vs. 3.3 +/- 1.3 minutes, 2.6 +/- 1.4 vs. 2.0 +/- 0.7 hours, respectively).
CONCLUSIONS
The increased Cl of fentanyl in those with burns is primarily dependent upon the resultant increased hepatic blood flow. The pulmonary kinetics is a saturable process, which is not affected by a single bolus of fentanyl. The lung injury induced by major burns would have no influence on the elimination kinetics of fentanyl.