2004 Annual Scientific Meeting - CLICK FOR PROGRAMME

Delivery of Remifentanil by Target-Controlled Infusion in Obese Patients is Influenced by the Method of Calculation of Lean Body Mass

John B Glen, Research Department, Glen Pharma Ltd, Knutsford, Cheshire WA16 0DZ. United Kingdom

Introduction:  Minto et al [1] described a pharmacokinetic model for remifentanil which uses age and lean body mass (LBM) as covariates.  While examining the delivery of remifentanil by target-controlled infusion (TCI), an anomaly was observed in that for patients of a given height, LBM began to decrease above a certain body weight. This led to a systematic evaluation of the influence of gender, height and weight on LBM as calculated by Minto and by an alternative method (Hume [2]).

Methods: Both methods calculate LBM from weight (kg) and height (cm).  Minto’s equation for males is 1.1.weight-128.(weight/height)² and for females 1.07.weight- 148.(weight/height)².  The method described by Hume  gives LBM in males as 0.32810.weight + 0.33929.height - 29.5336 and in females as 0.29569.weight + 0.41813.height - 43.2933.  Using both methods, plots were derived to display the influence of body weight (30-150 kg) on LBM for male and female patients with heights of 140, 160, 170 and 180 cm.  Computer simulation (PK-SIM) was used to illustrate the influence of the different methods of LBM calculation on remifentanil TCI delivery with the Minto model.

Results:  For a given height of patient, the Hume equations provide a linear relationship between LBM and weight, whereas with the Minto equations, LBM reaches a maximum value and then declines as body weight increases further (Fig)

Fig. Influence of weight on calculation of LBM in a 160 cm, 40 y female with Minto and Hume calculations of LBM.

Examination of the Minto plots indicated that the point of inflexion occurred at body mass index (BMI) values close to 35 kg.m² in females and 40 kg.m² in males.  In a 70 kg, 160 cm, 40 year old female (BMI 27.3 kg.m²) both methods estimate similar values for LBM. However, with the same height and age of patient but bodyweight 150kg (BMI 58.6 kg.m²), the Minto calculation estimates LBM as 30.4 kg versus the value of 70 kg obtained by Hume.  The amount of remifentanil delivered to maintain a target blood concentration of 10 ng.ml^-1 over 60 min with the Minto calculation (1.41 mg) is 13 % less than provided with the same model to the 70 kg patient and 27% less than the 1.93 mg provided using the Hume calculation.

Conclusion:  This anomaly in the calculation of LBM in the Minto model will have an influence only in morbidly obese patients with a potential risk of under delivery of drug requiring careful titration of the target setting to an individual patient’s requirements.  In future applications of TCI delivery, the Hume calculation of LBM may deserve further evaluation or consideration should be given to BMI as a covariate in PK modelling.

References:  1. Anesthesiology 1997;86:10. 2. J Clin Path 1966;19:389.