Study links pediatric sedation strategies to later neurocognitive outcomes

A new Penn Nursing study suggests that specific sedative medications used during critical illness in early childhood may have long-term effects on a child’s neurocognitive development. Martha Aque Curley, PhD, RN, FAAN, professor in the Department of Family and Community Health, and the Ruth M. Colkett Endowed Chair in Pediatric Nursing at the Children’s Hospital of Philadelphia. Seattle Children’s Hospital MD, R. Co-led the study with Scott Watson.

Research, published in jama network openfound that while most children who survived serious illness requiring sedation had IQ scores within the normal range, those who were treated only with a combination of opioids and benzodiazepines scored lower on subsequent neurocognitive tests than those whose treatment included the sedative dexmedetomidine.

Assessing Long-Term Impact

Critically ill young children often need to be sedated for several days or even weeks to tolerate life-saving treatments such as mechanical ventilation. Although these medications are essential, concerns remain about their potential toxicity on the developing brain.

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

key findings

• general cognitive function: The average estimated IQ of study participants was 100.3, which is in line with the general population average.
• Sedative tactics matter: When adjusting for factors such as socioeconomic status and severity of the original illness, children who received only opioids and benzodiazepines had an adjusted average IQ about four points lower than those who received dexmedetomidine as part of their care.
• Vulnerability to high doses: This difference was even more pronounced in children who required the highest doses of benzodiazepines; In this group, those treated only with opioids and benzodiazepines had IQ scores about eight points lower than those who also received dexmedetomidine.
• specific deficit: Beyond global IQ, researchers saw below-average scores in areas like non-verbal memory, visuospatial skills and fine motor control across the entire group of survivors.

clinical implications

For a long time, we have not had clear evidence about which sedative medications are best for critically ill children on ventilators. Our study shows that the choices we make in the pediatric ICU can impact a child’s brain development years later. In particular, adding dexmedetomidine to our treatment plan may help better protect a child’s long-term thinking and learning skills than using opioids and benzodiazepines alone.”

Martha Aque Curley, PhD, RN, FAAN, Professor, Department of Family and Community Health, Ruth M. Colkett 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 long-term neurocognitive follow-up research (MAQ Curley, RS Watson).

Co-authors 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 Harvard Medical School; Derek C. Angus, MD, MPH, of the University of Pittsburgh Medical Center; and R. of the University of Washington School of Medicine and Seattle Children’s Hospital. Scott Watson, MD, MPH.