Study links pediatric sedation strategies with later neurocognitive outcomes

A new Penn Nursing study suggests that the specific sedatives used during critical illness in early childhood may have long-term implications for a child's neurocognitive development. Martha A.Q. Curley, PhD, RN, FAAN, Professor in the Department of Family and Community Health, and the Ruth M. Colket Endowed Chair in Pediatric Nursing at Children's Hospital of Philadelphia. co-led the study with R. Scott Watson, MD, from Seattle Children's Hospital.

The research, published in JAMA Network Open, found that while most children who survived a critical illness requiring sedation had IQ scores within the normal range, those treated with a combination of only opioids and benzodiazepines scored lower on later neurocognitive tests than those whose treatment included the sedative dexmedetomidine.

Assessing long-term impact

Critically ill young children often require days or even weeks of sedation to tolerate life-saving treatments like mechanical ventilation. While these medications are necessary, concerns have persisted about their potential toxicity to the developing brain.

The RESTORE-Cognition Study followed 256 children who were age eight or younger when they were hospitalized for acute respiratory failure. Researchers conducted comprehensive neurocognitive testing-including assessments of IQ, memory, and attention-three to eight years after the children were discharged from the pediatric intensive care unit (PICU).

Key findings

• General Cognitive Function: The average estimated IQ of the study participants was 100.3, which is consistent with the general population mean.
• Sedative Strategy Matters: When adjusting for factors like socioeconomic status and the severity of the original illness, children who received only opioids and benzodiazepines had an adjusted mean IQ approximately four points lower than those who received dexmedetomidine as part of their care.
• Vulnerability in High Doses: The difference was even more pronounced in children who required the highest doses of benzodiazepines; in this group, those treated with only opioids and benzodiazepines had an IQ score nearly eight points lower than those who also received dexmedetomidine.
• Specific Deficits: Beyond global IQ, researchers observed lower-than-average scores in areas such as nonverbal memory, visuospatial skills, and fine motor control across the entire group of survivors.

Clinical implications

For a long time, we haven't had clear evidence on which sedatives are best for critically ill children on ventilators. Our study shows that the choice we make in the pediatric ICU can affect a child's brain development years later. Specifically, adding dexmedetomidine to our treatment plan may help protect a child's long-term thinking and learning skills better than using opioids and benzodiazepines alone."

Martha A.Q. Curley, PhD, RN, FAAN, Professor, Department of Family and Community Health, the Ruth M. Colket Endowed Chair in Pediatric Nursing, Children's Hospital of Philadelphia

The study highlights the importance of long-term follow-up for PICU survivors to identify and support children who may experience subtle but impactful neurocognitive challenges.

About the RESTORE-Cognition study

This multicenter, prospective cohort study was conducted as a follow-up to the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial, which took place in 31 PICUs across the United States. It was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) through grants U01 HL086622 (MAQ Curley), which funded the original RESTORE clinical trial, and R01 HD074757, which supported the long-term neurocognitive follow-up research (MAQ Curley, RS Watson).

Coauthors include Sue R. Beers, PhD, and Cheryl Burns, PhD, both of the University of Pittsburgh School of Medicine; Lisa A. Asaro, MS, Min Jung Koh, MD, MS, and David Wypij, PhD, from the Department of Cardiology at Boston Children's Hospital and the Harvard Medical School; Derek C. Angus, MD, MPH, of the University of Pittsburgh Medical Center; and R. Scott Watson, MD, MPH, of the University of Washington School of Medicine and Seattle Children's Hospital.