Prospective Validation Of The Eleveld TCI Model For Propofol In The Malaysian Obese Population

Research question 1. Is the newer Eleveld TCI model for propofol applicable in the Malaysian obese population? 2. What is the bias level measured trough median prediction error (MDAPE) when applied to the Malaysian obese individual? Problem Statement

1. No study done in South East Asian obese population
2. Most studies focus on a group of population which are of Caucasian race with different pheno and genotypes compared with Asian population
3. We aim to validate the claim of the developers of the Eleveld TCI model that the median absolute prediction error of this particular model is approximately 20% in all subtypes of populations focusing on the obese population

INTRODUCTION

Total intravenous anaesthesia (TIVA) the process of induction and mantainence of anaesthesia for patients undergoing surgical procedures without the use of volatile agents. Hypnotic agents and opioids may be utilized to assist in the administration of TIVA. Commonly used agents include the use of propofol and remifentanil combined use mainly due to its positive synergistic effect and its low context-sensitive half time(CSHT). [1] TIVA offer many advantageous properties in contrast to volatile agents which include better recovery profile, less post-operative nausea and vomiting and is more environmentally safe. [1] The goal of TIVA is to ensure adequate depth of anaesthesia and rapid recovery and therefore this combination is ideal to aid in our anaesthetic goal. General infusions and intermittent boluses of these agents may not be ideal as different patient demographics influence the rate of elimination and distribution of drugs in the system [2-3,7], hence targeted control infusions (TCI) were introduced in practice to ensure adequate plasma concentrations for induction and mantainence of anaesthesia.

Since the introduction of the Bristol Model for propofol infusions in 1988, various TCI pumps based on different pharmacokinetic models have been developed through the sequential sampling of blood anaesthetic agent levels of healthy volunteers to allow the formulation of different types of pharmacokinetic models. The most popular and currently used TCI model are the Marsh and the Schneider which administers its infusion based on plasma and effect-site respectively however, both of these models have their limitations as they are only suitable for adult use.[4-5] Besides being only suitable for adults, most of these models are formulated for the non-obese population with a body mass index(BMI) of less than 35 kg/m2 and is unable to provide accurate levels in obese individuals due to the altered pharmacokinetics in this population. Changes in the pharmacokinetics of the obese population may predispose patients to inaccuracies of dosing which may lead to awareness or excessive depth of anaesthesia which may cause adverse effects[5-6]. Until recently in 2014, a general pharmacokinetic model for propofol was formulated and was named the Eleveld model[2-3]. Comparing with previous models developed by utilizing healthy volunteers, Eleveld model was developed by combining pharmacokinetic data from multiple studies involving diverse groups of patients and clinical conditions. This allows the formulation of a single pharmacokinetic model from the aggregated data set which in turn provides better identification of plasma levels. The data available on the open TCI website were taken into consideration and a three compartmental pharmacokinetic model was created using the nonlinear mixed effects modeling software (NONMEM) and was referenced to a 170 cm in height and 70 kg non-obese individual[2,3]. Based on this reference individual, multiple data involving various groups of obese and non-obese patients undergoing TIVA were collected and analyzed through allometric scaling. Mathematical models were formulated to estimate the volume of each compartment and a general use model based on the weight of patients was designed termed the Eleveld TCI Model[2].