Trial reportPloS one2019
Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia.
Trial report in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- The effect of using dexmedetomidine versus morphine as sedation on long-term neurodevelopmental outcomes of encephalopathic neonates undergoing therapeutic hypothermia.Journal of perinatology : official journal of the California Perinatal Association · 2025Observational
- Scoping Review of Paediatric Population Pharmacokinetic Models of Morphine.Clinical pharmacokinetics · 2025Article
- Sedation and Pain Management in Neonates Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy.Children (Basel, Switzerland) · 2025Review
- Oral Clonidine-Based Strategy to Reduce Opiate Use During Cooling for Neonatal Encephalopathy: An Observational Study.The Journal of pediatrics · 2024Observational
- Sedation and anesthesia for imaging of the infant and neonate-a brief review.Pediatric radiology · 2024Review
- Analgesia and sedation strategies in neonates undergoing whole-body therapeutic hypothermia: A scoping review.PloS one · 2023Article
- Hemodynamic response to milrinone for refractory hypoxemia during therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy.Journal of perinatology : official journal of the California Perinatal Association · 2021Article
- Management of comfort and sedation in neonates with neonatal encephalopathy treated with therapeutic hypothermia.Seminars in fetal & neonatal medicine · 2021Review
- Morphine and fentanyl exposure during therapeutic hypothermia does not impair neurodevelopment.EClinicalMedicine · 2021Article
- Practical approaches to sedation and analgesia in the newborn.Journal of perinatology : official journal of the California Perinatal Association · 2021Review
- Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.Pediatric research · 2020Article
- Prediction of Drug Exposure in Critically Ill Encephalopathic Neonates Treated With Therapeutic Hypothermia Based on a Pooled Population Pharmacokinetic Analysis of Seven Drugs and Five Metabolites.Clinical pharmacology and therapeutics · 2020Observational
- Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen.British journal of clinical pharmacology · 2020Article
- Management of Multi Organ Dysfunction in Neonatal Encephalopathy.Frontiers in pediatrics · 2020Review
- Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review.BMJ paediatrics open · 2020Review
- Hypothermia: Impact on plasticity following brain injury.Brain circulationReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 12 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMorphine 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
designTerm 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.
results244 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.
conclusionsClearance 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.
trial registrationwww.trialregister.nl NTR2529.
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