Randomized cross-over clinical trial comparing two pharmacokinetic models of propofol using entropy indices

Abstract

IntroductionThere are two different pharmacokinetic models (Marsh and Schnider) for the administration of total intravenous anesthesia with propofol, the parameter differences could have some impact over the depth of anesthesia. ObjectiveTo determine if there is a significant difference in the variability of depth of anesthesia suggesting that one model is superior in achieving a more stable and predictable depth of anesthesia during surgery. MethodsA cross-over clinical trial was conducted on 16 healthy patients programmed for upper or lower limb ambulatory orthopedic surgery. Patients were randomly assigned to (i) effect site target controlled infusion of propofol with Marsh model at a target concentration of 2.5μg/ml for 20min, a 20min washout, then propofol was administered with Schnider model at the same effect site target for the reminder of the surgery, or (ii) the reverse sequence. Differences in variability of depth of anesthesia, were assessed by comparing records of spectral entropy indices during surgery through an unpaired t-test. ResultsThere was no evidence of significant difference in the mean variances of either spectral entropy indices between the two models (p-value: 0.57 for State Entropy, p-value: 0.51 for Response Entropy). ConclusionThe study suggests that both pharmacokinetic models are equivalent in terms of stability of depth of anesthesia. It is important to keep testing determinants of the efficacy of the models in different types of population because their behavior according to individual characteristics of patients or variables such as cost-effectiveness could end up tilting the scale.