Performance of target-controlled sufentanil infusion in obese patients.
BACKGROUND
Because obesity might affect pharmacokinetic parameters, the authors evaluated the accuracy of target-controlled sufentanil infusion in morbidly obese patients using a pharmacokinetic model usually applied to a normal-weight population.


METHODS
Target-controlled propofol and sufentanil coinfusions were administered to 11 morbidly obese patients (body mass index: 45.0 +/- 6.5 kg/m2 ) undergoing laparoscopic gastroplasty. The target plasma propofol concentration was 3 micro g/ml. The effect-site sufentanil target concentration was initially 0.4 ng/ml but was modified during surgery as a function of blood pressure and heart rate. Plasma sufentanil concentrations were measured from the onset of infusion until 24 h after its termination. The predicted sufentanil target concentrations were calculated by STANPUMP software. Intrasubject data analyzed included calculation of performance error, median performance error, median absolute performance error, divergence, and wobble. Pharmacokinetic analysis was performed using a nonlinear mixed effect model.


RESULTS
Applied sufentanil target concentrations ranged from 0.3 to 0.65 ng/ml. The mean +/- SD plasma sufentanil concentration measured during spontaneous ventilation was 0.13 +/- 0.03 ng/ml. Median performance error (range) was -13% (-42 to 36%). Median absolute performance error was 26% (8-44%) during infusion and 17% (12-59%) for the 24 h after its completion. The pharmacokinetic sets used slightly overpredicted the concentrations, with a median divergence of -3.4% (-10.2 to 3.1%) during infusion. For body mass index greater than 40, the overestimation of plasma sufentanil concentrations was greater. A two-compartment model with proportional error for interindividual variability best fitted the data. The residual variability was modeled as an additive (0.016 ng/ml) or proportional error (23%). Clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution (coefficient of variation) were 1.27 l/min (23%), 37.1 l (20%), 0.87 l/min (44%), and 92.7 l (22%), respectively.


CONCLUSIONS
The pharmacokinetic parameter set derived from a normal-weight population accurately predicted plasma sufentanil concentrations in morbidly obese patients.
Slepchenko
Gregory
G
Department of Anesthesiology, Centre Hospitalier Universitaire, Nice, France. anesthesiologie@chu.nice.fr
Simon
Nicolas
N
Goubaux
Bernard
B
Levron
Jean-Claude
JC
Le Moing
Jean-Pierre
JP
Raucoules-Aimé
Marc
M
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D005260:Female; D015391:Gastroplasty; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009767:Obesity, Morbid / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D011229:Preanesthetic Medication; D017409:Sufentanil / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D017409:Sufentanil; D010100:Oxygen