Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients

A. Rolle, S. Paredes, L. I. Cortínez*, B. J. Anderson, N. Quezada, S. Solari, F. Allende, J. Torres, D. Cabrera, V. Contreras, J. Carmona, C. Ramírez, A. M. Oliveros, M. Ibacache

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. Methods: Forty patients, ASA I–III, 18–60 yr old, weighing 47–126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. Results: A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=–5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). Conclusions: We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. Clinical trial registration: NCT02557867.

Original languageEnglish
Pages (from-to)969-977
Number of pages9
JournalBritish Journal of Anaesthesia
Volume120
Issue number5
DOIs
StatePublished - May 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 British Journal of Anaesthesia

Keywords

  • anaesthetics i.v.
  • dexmedetomidine
  • obesity
  • pharmacokinetics

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