Related Experiment Video
Updated: May 20, 2026
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Sedative Choice and Neurocognitive Outcomes After Critical Illness in Early Childhood
Martha A Q Curley1,2, Sue R Beers3, Lisa A Asaro4
1School of Nursing, University of Pennsylvania, Philadelphia.
Insights
Pediatric intensive care unit (PICU) sedation with opioids and benzodiazepines was linked to lower long-term IQ scores in children. Including dexmedetomidine in sedation strategies may improve neurocognitive outcomes in critically ill young children.
Area of Science:
- Pediatric critical care medicine
- Neuroscience
- Pharmacology
Background:
- Sedatives are frequently used in critically ill children.
- Potential for sedatives to negatively impact early brain development.
Purpose of the Study:
- To examine the association between sedative choice in early childhood critical illness and long-term neurocognitive function.
Main Methods:
- Prospective cohort study of children aged 8 years or younger with acute respiratory failure.
- Neurocognitive testing (IQ) conducted 3-8 years post-hospitalization.
- Analysis adjusted for baseline factors, illness severity, and mechanical ventilation duration.
Main Results:
- IQ scores were similar to the general population.
- Opioid- and benzodiazepine-only sedation was associated with lower IQ compared to strategies including dexmedetomidine.
- Adjusted mean IQ difference was -4.1 (95% CI, -7.3 to -0.9) between opioid/benzodiazepine-only and dexmedetomidine groups.
Conclusions:
- Long-term IQ in children receiving over a week of PICU sedation was comparable to the general population.
- Sedation strategies including dexmedetomidine were associated with higher IQ scores than opioid- and benzodiazepine-only strategies.
- Findings suggest sedative choice may influence neurocognitive development in critically ill children.
Importance:
Sedatives, commonly administered in the clinical treatment of young children with critical illness, may be harmful to early brain development.
Objective:
To investigate whether sedative choice during critical illness in early childhood is associated with long-term neurocognitive function.
Design, Setting, And Participants:
This prospective cohort study was conducted among a subset of cognitively appropriate children with acute respiratory failure who were aged 8 years or younger when enrolled in the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) cluster-randomized clinical trial conducted in 31 pediatric intensive care units (PICUs) comparing a nurse-implemented, goal-directed sedation protocol with usual care. Patients underwent neurocognitive testing 3 to 8 years after hospitalization at regional neuropsychology testing centers. Neurocognitive testing was conducted from February 16, 2015, to November 27, 2018. Assessors were blinded to the sedation provided. Data were analyzed from September 2022 to March 2026.
Exposures:
Critical illness and sedation.
Main Outcomes And Measures:
The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Drug- and dose-dependent associations between sedatives and neurocognitive function were assessed, adjusting for baseline factors and severity and course of critical illness.
Results:
Neurocognitive testing was performed among 256 children (median [IQR] age, 6.6 [5.4 to 9.0] years). Among 243 children with data, 228 children (93.8%) had age-appropriate global assessment of cognitive function (Pediatric Cognitive Performance Category = 1) at testing. Children were exposed to a median (IQR) of 8 (5 to 14) days of continuous sedation at a median (IQR) age of 1.0 (0.2 to 3.2) years. The mean (SD) estimated IQ was 100.3 (13.2), similar to the published test mean of 100. Mean (SD) estimated IQ at long-term follow-up was lowest in patients receiving an opioid- and benzodiazepine-only strategy (98.3 [11.8]), higher in patients receiving multiple sedative classes not including dexmedetomidine (100.6 [14.5]), and highest in patients receiving multiple sedative classes, including dexmedetomidine (101.9 [13.5]). Controlling for Hollingshead Socioeconomic Status score, severity of illness on PICU admission, and duration of mechanical ventilation, the adjusted mean difference in estimated IQ between the opioid- and benzodiazepine-only vs dexmedetomidine groups was -4.1 (95% CI, -7.3 to -0.9; P = .01).
Conclusions And Relevance:
In this study of young children who received more than a week of PICU sedation, the estimated IQ was similar to that of the general population. Children who received an opioid- and benzodiazepine-only strategy scored lower than those who received a strategy that included dexmedetomidine when controlling for socioeconomic status, illness severity, and duration of mechanical ventilation.
Trial Registration:
ClinicalTrials.gov Identifier: NCT02225041.
