Prevention and treatment of traumatic brain injury-related delirium: a systematic review

Background Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury (TBI)-related delirium in acute care. Methods We searched four electronic databases (MEDLINE, EMBASE, CENTRAL/CDSR, and PsycINFO) to identify randomized controlled trials (RCTs), quasi-experimental, and observational studies. Eligible studies included adults with TBI, at least one comparator group, delirium as an outcome and took place in acute care. Two reviewers independently completed all study screening, data abstraction, and risk of bias assessment using the Cochrane risk of bias 2 tool for RCTs or risk of bias in non-randomized studies—of interventions tool for observational studies. We implemented the PROGRESS-Plus framework to describe social determinants of health (SDoH) reporting. Results We identified 20,022 citations, reviewed 301 in full text, and included eight studies in the descriptive synthesis. The mean age of study participants ranged from 32 to 62 years. 12.5% of included studies reported SDoH. Included studies had moderate-to-high risk of bias. Studies compared reorientation programs and an intervention bundle to usual care, but these interventions were not better than usual care in treating TBI-related delirium. Individual studies found that rosuvastatin and aripiprazole were more efficacious than placebo, and dexmedetomidine was more efficacious than propofol and haloperidol for preventing TBI-related delirium. No studies reported safety as the primary outcome. Conclusions We identified efficacious pharmacologic interventions for preventing TBI-related delirium, but these studies were at moderate-to-high risk of bias, which limits our confidence in these findings. Future studies should incorporate safety outcomes, and a diverse study population, including older adults.