External validation of pharmacokinetic population model of alfentanil in obese patients.
Amélie Marsot (1), Edith Ramain (2), Olivier Perus (2), Nicolas Simon (1)
(1) Laboratoire de pharmacologie médicale et clinique APHM, Université de la méditerranée, Marseille, France; (2) Département d’Anesthésie-Réanimation, Hôpital de l’Archet II, Nice, France.
Objectives: Alfentanil is a short-acting opioid commonly used in anesthesia with a target-controlled infusion (TCI). This method uses a model previously described in a population with a normal BMI [1]. An external validation was performed to check if this model was accurate in a population of obese patients.
Methods: Ten obese patients (weight: 99-145kg) undergoing laparoscopic gastroplasty and five normal weight patients undergoing surgery, aged 18 to 68 years were studied. Anesthesia was induced with propofol (2.5mg/kg) and TCI of alfentanil calculated with Stanpump software. The effect-site alfentanil target concentration was initially 100ng/l but was modified during surgery as a function of blood pressure and cardiac frequency. Blood samples were collected at 1 and 5 minutes after the start of infusion and at 0, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 180, 220 and 300 minutes after the definitive stop of infusion. Blood alfentanil concentrations were determined with a gas chromatography method. Pharmacokinetic analysis was made by using a non linear mixed-effect population model. Data analysing included calculation of performance error (PE), median performance error (MDPE) and median absolute performance error (MDAPE).
Results: A three compartment model with two covariates [1]: age (clearance and K31) and sex (volume of distribution of the central compartment), gave the following results. MDPE (range) was 29.94% (-47.70 to 225.67%) during infusion and 39.84% (-98.68 to 350.4%) after infusion. MDAPE (range) was 34.88% (0.60 to 225.67%) during infusion and 25.09% (0.60 to 350.4%) after infusion. This pharmacokinetic model underestimated the predicted concentrations. Another model including two covariates with three compartments was proposed: age (K12) and weight (K13). MDPE (range) was -5.33% (-58.39 to 74.59%) during infusion and -10.75% (-81.53 to 263.20%) after infusion. And MDAPE (range) was 8.99% (0.65 to 74.59%) during infusion and 31.77% (0.02 to 263.20%) after infusion. This model significantly improved the prediction of the high concentrations (during infusion).
Conclusions: For alfentanil infusion in morbidly obese individuals, a pharmacokinetic model deriving from normal weight patients underestimated the predicted concentrations. The proposed model gave interesting results which could be used to predict more efficiently concentrations for obese patients.
References:
[1] P. Maitre et al. Anesthesiology 1987; 66:3-12.
