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The purpose of this prospective, randomized, double-blind study was to determine the predictive performance of target-controlled infusions of propofol in morbidly obese patients using the ‘Marsh’ pharmacokinetic parameter set.Twenty-four patients (ASA II or III, age 25–62 years, BMI 35.5–61.7) were randomly allocated to receive propofol target-controlled infusion based on a weight adjustment formula (group adjusted) or without adjustment [group total body weight (TBW)]. Anaesthesia was induced by a propofol-targeted concentration of 6 μg ml−1 that was subsequently adapted to maintain stable bispectral index values ranging between 40 and 50. Arterial blood samples were collected before the start of the infusion and every 15 min thereafter to determine the predictive performances.There were no statistically significant differences between the groups with regard to performance errors, divergence and wobble. Results are presented as median (interquartiles). Median performance error and median absolute performance error were −31.7 (−35.9, −19.4) and 31.7% (20.2, 35.9) for group adjusted and −16.3 (−26.3, 2.2) and 20.6% (14.8, 26.9) for group TBW, respectively. Wobble median value was 7.4% (3.8, 8.4) for group adjusted and 8.2% (7.0, 9.6) for group TBW. As for wobble and divergence, no statistically significant differences were found between groups.Weight adjustment causes a clinically unacceptable performance bias, which is not corrected when TBW is used as an input to the ‘Marsh’ model. It is, therefore, advisable to administer propofol to morbidly obese patients by titration to targeted processed-EEG values.