Data from: Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia

  • Laurent M. A. Favié (Creator)
  • Floris Groenendaal (Creator)
  • Filip Cools (Creator)
  • Marcel P.H. Van Den Broek (Creator)
  • Carin M. A. Rademaker (Creator)
  • Timo R de Haan (Creator)
  • Henrica LM van Straaten (Creator)
  • Peter H Dijk (Creator)
  • Arno Van Heijst (Creator)
  • Jeroen Dudink (Creator)
  • Koen P Dijkman (Creator)
  • Monique Rijken (Creator)
  • Inge A. Zonnenberg (Creator)
  • Alexandra Zecic (Creator)
  • Johanna H. van der Lee (Creator)
  • Debbie H.G.M. Nuytemans (Creator)
  • Frank van Bel (Creator)
  • Toine C. G. Egberts (Creator)
  • Alwin Huitema (Creator)

Dataset

Abstract

Objective: Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population. Study design: Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008-2010 (SHIVER) and 2010-2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants. Results: 244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C – 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C – 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia. Conclusions: Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.
Datum van beschikbaarheid15 feb 2019
UitgeverDRYAD
Datum van data-aanmaak15 feb 2019

Format

  • Format
  • Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia.

    PharmaCool study group, Favié, LMA., Groenendaal, F., van den Broek, MPH., Rademaker, CMA., de Haan, TR., van Straaten, H., Dijk, PH., Van Heijst, A., Dudink, J., Dijkman, KP., Rijken, M., Zonnenberg, IA., Cools, F., Zecic, A., van der Lee, JH., Nuytemans, D., Van Bel, F., Egberts, T. CG. & Huitema, ADR., 14 feb 2019, In: PLoS ONE. 14, 2, 17 blz., 0211910.

    Onderzoeksoutput: Articlepeer review

    Open Access
    15 Citaten (Scopus)

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