Predictive performance of the 'Minto' remifentanil pharmacokinetic parameter set in morbidly obese patients ensuing from a new method for calculating lean body mass

Clin Pharmacokinet. 2010;49(2):131-9. doi: 10.2165/11317690-000000000-00000.

Abstract

Background and objectives: In a previous article, we showed that the pharmacokinetic set of remifentanil used for target-controlled infusion (TCI) might be biased in obese patients because it incorporates flawed equations for the calculation of lean body mass (LBM), which is a covariate of several pharmacokinetic parameters in this set. The objectives of this study were to determine the predictive performance of the original pharmacokinetic set, which incorporates the James equation for LBM calculation, and to determine the predictive performance of the pharmacokinetic set when a new method to calculate LBM was used (the Janmahasatian equations).

Methods: This was an observational study with intraoperative observations and no follow-up. Fifteen morbidly obese inpatients scheduled for bariatric surgery were included in the study. The intervention included manually controlled continuous infusion of remifentanil during the surgery and analysis of arterial blood samples to determine the arterial remifentanil concentration, to be compared with concentrations predicted by either the unadjusted or the adjusted pharmacokinetic set. The statistical analysis included parametric and non-parametric tests on continuous variables and determination of the median performance error (MDPE), median absolute performance error (MDAPE), divergence and wobble.

Results: The median values (interquartile ranges) of the MDPE, MDAPE, divergence and wobble for the James equations during maintenance were -53.4% (-58.7% to -49.2%), 53.4% (49.0-58.7%), 3.3% (2.9-4.7%) and 1.4% h(-1) (1.1-2.5% h(-1)), respectively. The respective values for the Janmahasatian equations were -18.9% (-24.2% to -10.4%), 20.5% (13.3-24.8%), 2.6% (-0.7% to 4.5%) and 1.9% h(-1) (1.4-3.0% h(-1)). The performance (in terms of the MDPE and MDAPE) of the corrected pharmacokinetic set was better than that of the uncorrected one. The predictive performance of the original pharmacokinetic set is not clinically acceptable. Use of a corrected LBM value in morbidly obese patients corrects this pharmacokinetic set and allows its use in obese patients. The 'fictitious height' can be a valid alternative for use of TCI infusion of remifentanil in morbidly obese patients until commercially available infusion pumps and research software are updated and new LBM equations are implemented in their algorithms.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacokinetics*
  • Body Mass Index*
  • Female
  • Humans
  • Infusions, Parenteral / methods
  • Middle Aged
  • Models, Statistical
  • Obesity, Morbid / drug therapy*
  • Piperidines / administration & dosage
  • Piperidines / pharmacokinetics*
  • Prospective Studies
  • Remifentanil

Substances

  • Analgesics, Opioid
  • Piperidines
  • Remifentanil