Pharmacokinetics of propofol in severely obese surgical patients

Martin Rygh Braathen*, Ann E. Rigby-Jones, Johan Ræder, Olav Spigset, Tom Heier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Existing PK models of propofol include sparse data from very obese patients. The aim of this study was to develop a PK model based on standardised surgical conditions and spanning from normal-weight up to, and including, a high number of very obese patients. Methods: Adult patients scheduled for laparoscopic cholecystectomy or bariatric surgery were studied. Anaesthesia was induced with propofol 2 mg/kg adjusted body weight over 2 min followed by 6 mg/kg/h adjusted body weight over 30 min. For the remainder of the operation anaesthesia was maintained with sevoflurane. Remifentanil was dosed according to clinical need. Eight arterial samples were drawn in a randomised block sampling regimen over a span of 24 h. Time-concentration data were analysed by population PK modelling using non-linear mixed-effects modelling. Results: Four hundred and seventy four serum propofol concentrations were collected from 69 patients aged 19–60 years with a BMI 21.6–67.3 kg/m2. Twenty one patients had a BMI above 50 kg/m2. A 3-compartment PK model was produced wherein three different body weight descriptors and sex were included as covariates in the final model. Total body weight was found to be a covariate for clearance and Q3; lean body weight for V1, V2 and Q2; predicted normal weight for V3 and sex for V1. The fixed allometric exponent of 0.75 applied to all clearance parameters improved the performance of the model. Accuracy and precision were 1.4% and 21.7% respectively in post-hoc performance evaluation. Conclusion: We have developed a new PK model of propofol that is suitable for all adult weight classes. Specifically, it is based on data from an unprecedented number of individuals with very high BMI.

Original languageEnglish
Pages (from-to)726-736
Number of pages11
JournalActa Anaesthesiologica Scandinavica
Volume68
Issue number6
DOIs
Publication statusPublished - 13 Mar 2024

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Keywords

  • Anaesthetics i.v. propofol
  • bariatric surgery
  • obesity
  • pharmacokinetics
  • target-controlled infusion
  • Bariatric Surgery
  • Body Mass Index
  • Obesity
  • Body Weight
  • Humans
  • Middle Aged
  • Cholecystectomy, Laparoscopic
  • Male
  • Propofol/pharmacokinetics
  • Obesity, Morbid/surgery
  • Young Adult
  • Anesthetics, Intravenous/pharmacokinetics
  • Models, Biological
  • Adult
  • Female
  • Remifentanil/pharmacokinetics

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