ArticleCritical care explorations2020
Potential Neurodevelopmental Effects of Pediatric Intensive Care Sedation and Analgesia: Repetitive Benzodiazepine and Opioid Exposure Alters Expression of Glial and Synaptic Proteins in Juvenile Rats.
Article in Critical care explorations, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Daily Sedation Interruption vs Continuous Sedation in Pediatric Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.JAMA network open · 2024Pooled it
- Early Cognitive Function after Deep Sedation Using Different Anesthetic Agents in Pediatric Patients: A Prospective, Randomized Controlled Trial.Medicina (Kaunas, Lithuania) · 2024Trial
- Efficacy and safety of levetiracetam intravenous infusion combined with midazolam continuous pump infusion for stepwise emergency treatment of convulsive status epilepticus in children: a retrospective cohort study.American journal of translational research · 2026Article
- Comprehensive characterization of chronic midazolam exposure on neonates and long-term neurodevelopment.Molecular psychiatry · 2025Article
- 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
- Efficacy and safety of analgosedation with dexmedetomidine in critically ill mechanically ventilated children: a systematic review and meta-analysis of randomized controlled trials.Intensive care medicine. Paediatric and neonatal · 2025Article
- Early Postnatal Exposure to Midazolam Causes Lasting Histological and Neurobehavioral Deficits via Activation of the mTOR Pathway.International journal of molecular sciences · 2024Article
- Exposure to Sedation and Analgesia Medications: Short-term Cognitive Outcomes in Pediatric Critical Care Survivors With Acquired Brain Injury.Journal of intensive care medicine · 2024Article
- Medication Usage Record-Based Predictive Modeling of Neurodevelopmental Abnormality in Infants under One Year: A Prospective Birth Cohort Study.Healthcare (Basel, Switzerland) · 2024Article
- Machine learning to predict poor school performance in paediatric survivors of intensive care: a population-based cohort study.Intensive care medicine · 2023Article
- Effects of Morphine on Gp120-induced Neuroinflammation Under Immunocompetent Vs. Immunodeficient Conditions.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Article
- Body size and brain volumetry in the rat following prolonged morphine administration in infancy and adulthood.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Neurotoxic Impact of Individual Anesthetic Agents on the Developing Brain.Children (Basel, Switzerland) · 2022Review
- Decoding the Synaptic Proteome with Long-Term Exposure to Midazolam during Early Development.International journal of molecular sciences · 2022Article
- Comfort-holding in critically ill children: a scoping review.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2021Article
- Transitions from short to long-term outcomes in pediatric critical care: considerations for clinical practice.Translational pediatrics · 2021Review
- Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit.Frontiers in behavioral neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sedatives are suspected contributors to neurologic dysfunction in PICU patients, to whom they are administered during sensitive neurodevelopment. Relevant preclinical modeling has largely used comparatively brief anesthesia in infant age-approximate animals, with insufficient study of repetitive combined drug administration during childhood. We hypothesized that childhood neurodevelopment is selectively vulnerable to repeated treatment with benzodiazepine and opioid. We report a preclinical model of combined midazolam and morphine in early childhood age-approximate rats.
designAnimal model.
settingBasic science laboratory. SUBJECTS: Male and female Long-Evans rats.
interventionsInjections of morphine + midazolam were administered twice daily from postnatal days 18-22, tapering on postnatal days 23 and 24. Control groups included saline, morphine, or midazolam. To screen for acute neurodevelopmental effects, brain homogenates were analyzed by western blot for synaptophysin, drebrin, glial fibrillary acidic protein, S100 calcium-binding protein B, ionized calcium-binding adaptor molecule 1, and myelin basic proteins. Data analysis used Kruskal-Wallis with Dunn posttest, with a MEASUREMENTS AND MAIN
resultsMorphine + midazolam and morphine animals gained less weight than saline or midazolam (
conclusionsAnalysis of brain tissue in this novel rodent model of repetitive morphine and midazolam administration showed effects on synaptic, astrocytic, microglial, and myelin proteins. These findings warrant further investigation because they may have implications for critically ill children requiring sedation and analgesia.
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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.