Estimation of piperacillin clearance with different glomerular filtration rate formulas in critically ill children

Br J Clin Pharmacol. 2021 Mar;87(3):1275-1281. doi: 10.1111/bcp.14505. Epub 2020 Aug 19.

Abstract

Aims: Glomerular filtration rate (GFR) is difficult to assess in critically ill children using gold standard method and alternatives are needed. This study aimed to determine the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children, using a published piperacillin pharmacokinetics (PK) population model.

Methods: All children hospitalized in the paediatric intensive care unit of a single institution who were receiving piperacillin were included. PK were described using the nonlinear mixed effect modelling software MONOLIX. In the initial PK model, GFR was estimated according to the Schwartz 1976 formula. We evaluated a set of 12 additional validated formulas, developed using plasma creatinine and/or cystatin C concentrations, in the building model to assess the lowest between-subject variability for piperacillin clearance.

Results: We included 20 children with a median (range) postnatal age of 1.9 (0.1-19) years, body weight of 12.5 (3.5-69) kg. Estimated GFR according to the Schwartz 1976 formula was 160.5 (38-315) mL min-1 1.73 m-2 . Piperacillin clearance was best predicted by the Bouvet combined formula.

Conclusion: The combined Bouvet formula was the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children.

Keywords: clearance; creatinine; cystatin C; paediatric intensive care unit; renal elimination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Creatinine
  • Critical Illness*
  • Glomerular Filtration Rate
  • Humans
  • Infant
  • Kidney Function Tests
  • Piperacillin*
  • Young Adult

Substances

  • Creatinine
  • Piperacillin