Long-term Neurocognitive Outcomes after Pediatric Intensive Care Unit Admission: Exploring the Role of Drug Exposure

ABSTRACT Introduction Concerns exist regarding the impact of widely-used clinical drugs on brain development. This study investigates long-term neurocognitive functioning in relation to frequently used drug exposure at the Pediatric Intensive Care Unit (PICU). Methods This study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation (patient group, n=65) to a demographically comparable control group (n=76) on a broad range of neurocognitive outcomes. The patient group was selected because bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. The relation between exposure to sedatives, analgesics and anesthetics and neurocognitive outcomes was assessed by regression analyses. Results The patient group had lower intelligence than the control group (p<.001, d =-0.59) and poorer performance in neurocognitive functions; i.e. speed and attention (p=.009, d =-0.41) and verbal memory (p<.001, d =-0.60). Exposure to sedatives, analgesics and anesthetics was not related to neurocognitive outcomes. Conclusion Children with PICU admission for bronchiolitis requiring mechanical ventilation are at risk of long-term neurocognitive impairment. This study found no evidence for a role of exposure to sedatives, analgesics or anesthetics. Findings underline the importance of long-term follow-up after PICU admission, even in absence of disease with neurological manifestation. Category of study Clinical population study Impact Animal studies have indicated that exposure of the maturing brain to clinical drugs may cause neurodegeneration. Clinical studies show mixed evidence for an association between clinical drugs and neurocognitive outcomes. This study provides evidence for long-term neurocognitive impairment among children with a history of PICU admission for bronchiolitis, a condition that seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. We found no evidence for a relation between drug exposure (i.e. sedatives, analgesics and anesthetics) and long-term neurocognitive outcomes, suggesting that the observed neurocognitive impairments are not accounted for by drug exposure. Findings: underline the importance of structured follow-up after PICU admission, even in absence of disease with neurological manifestation.