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Assessing circadian rhythms during prolonged midazolam infusion in the pediatric intensive care unit (PICU) children

Agnieszka Bienert1, Alicja Bartkowska-Sniatkowska, Paweł Wiczling

  • 1Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Marii Magdaleny 14, PL 61-861 Poznań, Poland. agnbienert@op.pl.

Pharmacological Reports : PR
|April 9, 2013
PubMed

Insights

This study found no circadian rhythms in midazolam pharmacokinetics for pediatric intensive care unit (PICU) patients. Critically ill children

Area of Science:

  • Pharmacology
  • Circadian Biology
  • Pediatric Critical Care

Background:

  • Evaluating circadian rhythms in pediatric intensive care unit (PICU) patients receiving prolonged midazolam infusion.
  • Assessing the impact of mechanical ventilation on drug pharmacokinetics and physiological rhythms.

Purpose of the Study:

  • To investigate potential circadian variations in midazolam and its metabolite pharmacokinetics.
  • To analyze physiological parameters for rhythmic patterns in sedated, mechanically ventilated children.

Main Methods:

  • Blood samples collected for midazolam and 1-OH-midazolam assays.
  • Hourly monitoring of blood pressure, heart rate, and body temperature.
  • Population nonlinear mixed-effect modeling using NONMEM.

Main Results:

  • Midazolam and metabolite pharmacokinetics described by two- and one-compartment models, respectively.
  • Physiological parameter profiles showed disturbed or abolished 24-hour rhythms compared to healthy subjects.
  • No significant circadian rhythm detected for midazolam, its metabolite, or monitored physiological parameters.

Conclusions:

  • Light-dark cycle does not influence midazolam pharmacokinetics in PICU children.
  • Endogenous rhythms are severely disturbed and desynchronized in critically ill, sedated children.
  • Midazolam dosage adjustment to body weight is necessary; mechanical ventilation may reduce midazolam clearance.
Abstract

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