Pharmacokinetic mass of fentanyl for postoperative analgesia in lean and obese patients.

BACKGROUND: We previously proposed dosing weights for fentanyl, termed 'pharmacokinetic mass', that span the total body weight (TBW) range from 40 to 210 kg. In this study, we examined the relationships among fentanyl doses needed to achieve postoperative analgesia, corresponding plasma fentanyl concentrations, and pharmacokinetic mass in lean and obese patients undergoing abdominal surgery.

METHODS: A total of 69 patients were studied, with TBW ranging from 48 to 181 kg. Fentanyl infusion was used during surgery. After surgery, fentanyl infusion rates were titrated to achieve analgesia without significant respiratory depression. Plasma fentanyl concentrations were measured when an apparent steady analgesic state was obtained. Comparisons were made for dosing requirements and effective plasma concentrations for 37 lean patients (body mass index < 30, TBW < 85 kg) and 33 obese patients (body mass index > 30, TBW > or = 85 kg).

RESULTS: The average fentanyl dose (microg h(-1)) required to achieve and maintain analgesia over the 4 h postoperative period had a non-linear relationship to TBW; in comparison, fentanyl dose had a strong linear relationship to pharmacokinetic mass: dose (microg h(-1)) = 1.22 x pharmacokinetic mass - 7.5; r = 0.741, P < 0.001. Based on results from our earlier study, the corresponding values of TBW and pharmacokinetic mass are: 52 kg--52 kg; 70 kg--65 kg; 100 kg--83 kg; 120 kg--93 kg; 140 kg--99 kg; 160 kg--104 kg; 180 kg--107 kg; 200 kg--109 kg. In the group comparisons, there was no statistically significant difference in the postoperative fentanyl dose per unit of pharmacokinetic mass between lean and obese patients. The plasma concentration of fentanyl required for analgesia was approximately 1.5 ng ml(-1), and was similar in the two groups.

CONCLUSION: The relationship between dose and pharmacokinetic mass, compared with that of dose vs TBW, may provide confidence for the use of pharmacokinetic mass as a dosing approximation for fentanyl. Fentanyl dose based on TBW may cause overdosing in obese patients.