Trial reportBritish journal of anaesthesia2008
Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial.
Trial report in British journal of anaesthesia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
59 citing papers in PubMed, 4 syntheses or guidelines pooled it, 180 citations in OpenAlex.
- Pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates.The Cochrane database of systematic reviews · 2025Pooled it
- Opioid equipotency conversions for hospitalized infants: a systematic review.Journal of perinatology : official journal of the California Perinatal Association · 2024Pooled it
- Non-pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates.The Cochrane database of systematic reviews · 2024Pooled it
- Opioids for newborn infants receiving mechanical ventilation.The Cochrane database of systematic reviews · 2021Pooled it
- Quantifying the Pharmacodynamics of Morphine in the Treatment of Postoperative Pain in Preverbal Children.Journal of clinical pharmacology · 2022Trial
- Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.Clinical pharmacokinetics · 2020Trial
- Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia.PloS one · 2019Trial
- Pharmacokinetic models of morphine and its metabolites in neonates:: Systematic comparisons of models from the literature, and development of a new meta-model.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2016Trial
- Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium.Journal of clinical pharmacology · 2016Trial
- Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetic properties of conventional and double-dose sulfadoxine-pyrimethamine given as intermittent preventive treatment in infancy.Antimicrobial agents and chemotherapy · 2011Trial
- Response: Codeine in Breast Milk: Minimal Transfer, Still Risky for Neonates.Paediatric anaesthesia · 2026Article
- Codeine and Metabolite Concentrations in the Breastfed Neonate.Paediatric anaesthesia · 2026Review
- Codeine toxicity via breast Milk: Can this occur and implications for opiate therapy in children.British journal of clinical pharmacology · 2026Review
- The Coming of Age of Model-Informed Precision Therapeutics for Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Scoping Review of Paediatric Population Pharmacokinetic Models of Morphine.Clinical pharmacokinetics · 2025Article
- Exploring the Interactions Between Epidural Analgesia, Extubation and Reintubation Outcomes in Infants in Neonatal Care Units: A Retrospective Cohort Study.Children (Basel, Switzerland) · 2025Article
- The Cost of Opioid Use in High-Risk Hospitalized Infants.The Journal of surgical research · 2024Article
- Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US.JAMA network open · 2024Article
- Developing mathematical models to compare and analyse the pharmacokinetics of morphine and fentanyl.Indian journal of anaesthesia · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundRelationships between plasma morphine concentrations and neonatal responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates.
methodsVentilated preterm neonates (n=898) from 16 centres were randomly assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100 microg kg(-1)), morphine infusions [23-26 weeks postmenstrual age (PMA) 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); and 30-32 weeks 30 microg kg(-1) h(-1)] were established for a maximum of 14 days. Open-label morphine (20-100 microg kg(-1)) was given for pain or agitation. Morphine assay and neonatal response to ETT suctioning was measured at 20-28 and 70-76 h after starting the drug infusion and at 10-14 h after discontinuation of the study drug. The concentration-effect response was investigated using non-linear mixed effects models.
resultsA total of 5119 data points (1598 measured morphine concentrations and 3521 effect measures) were available from 875 neonates for analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA (CLmat(50)) and increased from 2.05 litre h(-1) 70 kg(-1) at 24 weeks PMA to 6.04 litre h(-1) 70 kg(-1) at 32 weeks PMA. The volume of distribution in preterm neonates was 190 litre 70 kg(-1) (CV 51%) and did not change with age. There was no relationship between morphine concentrations (range 0-440 microg litre(-1)) and heart rate changes associated with ETT suctioning or with the Premature Infant Pain Profile.
conclusionsA sigmoid curve describing maturation of morphine clearance is moved to the right in preterm neonates and volume of distribution is increased compared with term neonates. Morphine does not alter the neonatal response to ETT suctioning.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.