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

• Published in: Anesthesia and analgesia Vol. 115; no. 4; pp. 823 - 829
• Main Authors: ECHEVARRIA, Ghislaine C, ELGUETA, María F, DONOSO, María T, BUGEDO, Diego A, CORTINEZ, Luis I, MUNOZ, Hernan R
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.10.2012
• Subjects: Adult; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Body Weight - drug effects; Body Weight - physiology; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Intubation, Intratracheal - methods; Male; Medical sciences; Middle Aged; Models, Chemical; Obesity, Morbid - metabolism; Propofol - administration & dosage; Propofol - pharmacokinetics; Treatment Outcome; Human; Obesity; General anesthetic; Body weight; Nutrition disorder; Anesthesia; Intubation; Propofol; Pharmacokinetics; Nutritional status
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1213/ANE.0b013e31825d6254

Most pharmacokinetic (PK) models used for propofol administration are based on studies in normal-weight patients. Extrapolation of these models for morbidly obese patients is controversial. Using 2 PK models and a target-controlled infusion system, we determined the predicted propofol effect-site concentration (Ce) needed for induction of anesthesia in morbidly obese subjects using total body weight. Sixty-six morbidly obese subjects from 18 to 50 years of age were randomized to receive propofol to reach and maintain a predetermined propofol Ce, based on the PK models of either Marsh or Schnider. All patients were monitored with a Bispectral Index electroencephalographic monitor. Fentanyl 3 μg/kg total body weight was administered before starting the propofol infusion. After loss of consciousness, vecuronium was administered to facilitate endotracheal intubation. Groups of 6 patients each received propofol at a different, predetermined target propofol Ce. An "effective Ce" (ECe) was defined as the propofol Ce that provided adequate hypnosis (Bispectral Index <60) 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 1 minute throughout the study period. Probit regression analysis was performed to calculate the effective propofol Ce values to induce 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 μg/mL (95% CI: 2.9, 3.7 μg/mL) with the Marsh model and 4.5 μg/mL (95% CI: 4.1, 4.8 μg/mL) with the Schnider model (P < 0.001). The ECe(95) values were 4.2 μg/mL (95% CI: 3.8, 6.2 μg/mL) and 5.5 μg/mL (95% CI: 5.0, 7.2 μg/mL) with Marsh and Schnider models, respectively. At the ECe(95), hemodynamic effects were similar with 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.