The Effective Effect-Site Propofol Concentration for Induction in Morbidly Obese Patients Using Total Body Weight with a New Pharmacokinetic Model

Abstract

To the Editor: Recently Echevarría et al.1 from our group described the effect-site propofol concentration (Ce) required to be set in propofol effect-site target-controlled infusion mode to induce and intubate the tracheas of morbidly obese patients using total body weight (TBW) with the Marsh and the Schnider pharmacokinetic (PK) models.2,3 These models, however, were not derived from obese patient data and their use in obese patients is controversial. Using the same data from Echevarría et al.’s1 study, we estimated the propofol Ce to be set for induction and tracheal intubation with a new PK model available for obese patients.4 The data of 66 morbidly obese subjects aged from 18 to 50 years were analyzed. All patients were monitored with a bispectral index electroencephalographic monitor (A2000 BIS® XP monitor, version 3.2; Aspect Medical Systems Inc., Newton, MA). Fentanyl 3 μg/kg TBW was administered before starting propofol infusion. The Ce (CI95%) producing a bispectral index <60 until intubation for 50% (Ce50) and 95% (Ce95) of patients was calculated with logistic regression. The target values obtained were 3.8 (3.2–4.2) μg/mL and 5.6 (5.0–7.6) μg/mL, respectively. The mean dose of propofol estimated to reach the Ce within the range of confidence interval 95% of the Ce50 (n = 19) was 0.9 ± 0.1 and 1.6 ± 0.2 mg/kg for the Ce95 (n = 16). Mean maximum decrease of mean arterial blood pressure was around 30% with the 2 estimated Ces. Heart rate variations ranged from −22% to 12% from baseline. Figure 1 shows the concentration versus effect curves estimated for the 3 PK models.Figure 1: Dose-response curve fitted to Cortínez, Marsh, and Schnider pharmacokinetic models using logit analysis, based on total body weight. The y-axis corresponds to the probability of no response until tracheal intubation (TI) and the x-axis to the predicted propofol effect-site concentration (Ce).This new analysis suggests that when using propofol target-controlled infusion with the Cortínez PK model4 in morbidly obese patients receiving fentanyl 3 μg/kg TBW, the Ce for induction and intubation should be around 5.5 μg/mL. A significant decrease in arterial blood pressure must be expected with this recommended dosingscheme.