Effect-Site Target-Controlled Infusion in the Obese: Model Derivation and Performance Assessment

Abstract

We derived and validated a propofol PKPD model to perform effect-site TCI in obese patients. This model, derived exclusively from obese patient's data, is not recommended for TCI in lean patients because it carries the risk of underdosing.

Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia

“…We enrolled 25 subjects in each of the following four groups according to age, weight, or both: children (three age <18 yr), non-obese adults (18 age <70 yr; BMI < 30 kg m À2 ), older patients (age !70 yr), and obese adults (18 age <70 yr; BMI!30 kg m À2 ). Obese children and older subjects were not excluded.…”

“…An MdPE<20% and MdAPE<40% have been suggested to indicate clinically acceptable performance. 12,13 Other PK and PK-PD models for comparison (and patient groups) considered were the Schnider model 14 (adults, older subjects, obese) the Marsh model 15 (adults, older subjects, obese), the Marsh model with correction by Servin 16 (obese), the Cortinez model 17 (adults, older subjects, obese) and Cortinez 'obese' model 18 (obese), the Kataria model 19 (children), the Paedfusor model 20,21 (children), and the Araú jo model 22 (adults, older subjects, obese). We compared model differences in MdAPE i and Wobble i using a one-sided (other model performs better) Wilcoxon signed rank test.…”

Pharmacokinetics of propofol in severely obese surgical patients

“…Therefore, we believe the optimal way of constructing a PK model is to collect samples from a large number of patients with a wide range of body sizes from normal-weight to BMI > 60 kg/m 2 in the same study. 26,27 This becomes apparent in the present study where our model has a better fit compared to the one of Eleveld, when tested post hoc on the same data set. A comparison of patient body size characteristics in the Eleveld data set and the current study is presented in Table 6.…”

“…Van Kralingen et al did include 20 patients in their study with a mean body mass index of 43 kg/m 2 but did not take arterial concentration samples later than 150 min after the end of the propofol infusion, which may result in lower predicted distribution volume and shorter elimination half‐life 25 . Cortinez et al published a PK/PD model based on previous propofol studies that was prospectively tested against other models 26 . This model cannot be used in lean patients and did not perform as well as the Eleveld model in the performance evaluation on obese patients.…”

Anestesia intravenosa en urgencia

“…Los modelos de Propofol iniciales incluidos en los TCI (iniciales de Target Controlled Infusion) eran sencillos, éstos eran modelos poblacionales de distribución y eliminación que calculaban la concentración plasmática en base a una única covariable como el peso [1], pero ésta resultó ser una simplificación excesiva, siendo útil solo para población adulta joven y mesomorfa. Se empezaron a desarrollar entonces modelos de mayor exigencia, como incluir edades extremas y obesidad [2], [3], [4].…”