The Effective Effect-Site Propofol Concentration for Induction and Intubation With Two Pharmcokinetic Models in Morbidly Obese Patients Using Total Body Weight

Abstract

M ost pharmacokinetic (PK) models used for administering propofol are based on studies in normal-weight patients. Extrapolation of these models for morbidly obese patients is controversial. Aided by 2 PK models and a target-controlled infusion (TCI) system, the predicted propofol effect-site concentration (Ce) needed for induction of anesthesia was ascertained in morbidly obese subjects using total body weight. Sixty-six morbidly obese subjects (aged 18Y50 years) were randomly assigned to receive propofol to reach and maintain a predetermined Ce, based on the PK models of either Marsh or Schnider. All patients were monitored with a bispectral index (BIS) electroencephalographic monitor. Fentanyl 3 Kg/kg of total body weight was given before starting the propofol infusion. After consciousness was lost, vecuronium was administered to assist in endotracheal intubation. Groups of 6 patients each received propofol at a different predetermined target Ce. An Beffective Ce[ (ECe) was defined as the propofol Ce that provided adequate hypnosis (BIS G60) during the complete induction period (45 seconds after reaching the predetermined target Ce until 5 minutes after tracheal intubation). Heart rate and arterial blood pressure were measured every minute throughout the study. Probit regression analysis was performed to calculate the ECe values for inducing hypnosis in 50% (ECe 50 ) and 95% (ECe 95 ) of patients with 95% confidence intervals (CIs). Patient characteristics were similar between models and across the propofol target concentration groups. The ECe 50 of propofol was 3.4 Kg/mL (95% CI, 2.9Y3.7 Kg/mL) with the Marsh model and 4.5 Kg/mL (95% CI, 4.1Y4.8 Kg/mL) with the Schnider model. The ECe 95 values were 4.2 Kg/mL (95% CI, 3.8Y6.2 Kg/mL) and 5.5 Kg/mL (95% CI, 5.0Y7.2 Kg/mL) with Marsh and Schnider models, respectively. At the ECe 95 , hemodynamic effects were similar to those of the 2 PK models. Different propofol target concentrations for each PK model must be used for induction when using total body weight in morbidly obese patients. COMMENTThis study attempts to determine the appropriate target Ce to be used for induction and tracheal intubation based on total body weight in morbidly obese patients (body mass index Q40 kg/m 2 ). Obesity affects the PK of many anesthetic drugs. Currently, there is no consensus on the best way to calculate drug dosage in morbidly obese patients. The majority of PK models take into account only normal body weight. Propofol can be administered using a TCI system that would reach the Ce required for the induction phase of anesthesia. Although TCI systems grant better dosage manipulation, they require the input of many parameters including height, weight, gender, age, and the target Ce for the drug that will be used. In addition, TCI designs require an accurate PK model to be clinically useful. The 2 most commonly used PK models for propofol referred to in this study are those by Marsh and Schnider.The central volume is a critical parameter in determining induction and maintenance wi...