Sedative medications: a potentially modifiable risk factor for improving neurocognitive outcomes after critical...

Critically ill infants and children often need prolonged sedation to support life-saving therapeutic interventions. Although advances in pediatric intensive care (PICU) have substantially improved survival, an increasing body of evidence indicates that many survivors experience persistent neurocognitive and neurobehavioral impairments. These outcomes arise from a complex interplay between pre-morbid status, critical illness related physiological stressors and iatrogenic exposures during periods of brain development. Evidence consistently links benzodiazepines to increased risk of delirium, sleep fragmentation, withdrawal, and adverse cognitive trajectories in pediatric populations. In contrast, α ₂-adrenergic agonists such as dexmedetomidine may be associated with a lower risk of delirium, improved sleep architecture, and potential neuroprotective effects in preclinical and early clinical studies, although human evidence is conflicted with limited data in PICU. Although several studies have evaluated the long-term neurocognitive effects of inhaled anesthetics after general surgical anesthesia, their increasing use for PICU sedation remains understudied. This narrative review synthesizes preclinical and clinical literature examining the associations between sedation practices in PICUs and subsequent neurocognitive outcomes. We focus on potential modifiable contributors, including sedative class selection, sedative polypharmacy, sleep disruption, and delirium, while acknowledging non-modifiable risk factors such as developmental stage at illness onset, acute neurological injury, systemic inflammation, and non-clinical social determinants of health.