Long-term cognitive testing showed higher estimated IQ scores among pediatric patients exposed to dexmedetomidine-containing sedation regimens compared with among those managed with opioids and benzodiazepines alone, according to a cohort study.

Researchers evaluated 256 pediatric patients who participated in the RESTORE-Cognition prospective cohort study, which included those enrolled in the Randomized Evaluation of Sedation Titration for Respiratory Failure trial. The participants were aged 8 years or younger at pediatric intensive care unit (ICU) admission and underwent neurocognitive testing 3 to 8 years following hospitalization.

The primary outcome was estimated IQ derived from age-appropriate Wechsler Vocabulary and Block Design subtests. Assessors were blinded to the sedation provided. All of the participants received benzodiazepines. The researchers categorized sedation exposure into three groups: opioids and benzodiazepines only; multiple sedative classes including dexmedetomidine; and multiple sedative classes not including dexmedetomidine. More than one-third of the patients received four or more sedative classes.

Among 247 patients with primary outcome data, the mean estimated IQ of 100.3 was comparable to the published test mean of 100. After adjustment for Hollingshead socioeconomic status score, PRISM III-12 score, and duration of mechanical ventilation, the mean estimated IQ was 98.3 among the patients who received opioids and benzodiazepines only, 100.6 among those who received multiple sedative classes without dexmedetomidine, and 101.9 among those who received multiple sedative classes including dexmedetomidine. The adjusted mean estimated IQ was 4.1 points lower in the opioid-and-benzodiazepine-only group compared with in the group whose regimen included dexmedetomidine.

“[W]e also found that the sedative strategy used during the [pediatric ICU] stay was associated with estimated IQ scores,” wrote lead study author Martha A. Q. Curley, RN, PhD, of the School of Nursing at the University of Pennsylvania and the Research Institute of the Children’s Hospital of Philadelphia, and colleagues.

The researchers included pediatric patients who were treated at 31 pediatric ICUs. The participants received a median of 8 days of continuous sedation at a median age of 1 year and were tested a median of 5.3 years posthospitalization. Most were admitted with bronchiolitis or asthma (or reactive airway disease) or with pneumonia or aspiration pneumonia. The researchers noted that 57% of them had multiple organ dysfunction syndrome present on day 0 or 1 of mechanical ventilation.

There were no statistically significant differences in the estimated IQ according to cumulative benzodiazepine dose tertile or cumulative opioid dose tertile after adjustment. The researchers also found no significant differences in estimated IQ according to age category at pediatric ICU admission.

Although mean estimated IQ was similar to the published test mean, the cohort scored lower than the published test means in several neurocognitive domains, including nonverbal memory, visuospatial skills, attention, and psychomotor skills. The cohort scored higher than the test mean on expressive language testing.

In adjusted analyses, the pediatric patients whose sedation strategy included dexmedetomidine had higher expressive language scores compared with those who received an opioid- and benzodiazepine-only strategy.

The study has several limitations. The researchers did not have neurocognitive assessments prior to hospitalization, so the extent to which the findings reflected the critical illness itself could not be determined with certainty. Patients with known neurocognitive dysfunction were excluded, limiting generalizability. The study estimated IQ using two Wechsler subscales rather than full-scale IQ testing. Not all eligible participants completed long-term follow-up or neurocognitive testing, potentially reducing study power and introducing selection bias. The researchers additionally noted that observational studies cannot definitively establish causality between exposures and outcomes.

The study authors reported no conflicts of interest. The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; and the National Institute of Nursing Research of the National Institutes of Health.

Source: JAMA Network Open