Different depths of sedation versus risk of delirium in adult mechanically ventilated patients: A systematic review and meta-analysis

BACKGROUND: Delirium is multifactorial. This study aimed at determining the association between different depths of sedation and the risk of delirium in adult mechanically ventilated patients. METHODS: A systematic literature retrieval was conducted in databases including Cochrane Central Register of Controlled Trials, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature for publications available till December 2019 without limitation in study type, and followed by a secondary retrieval for related literature. STATA15.1 and WinBugs 14.3 were used in statistical analyses for different sedation depths as the intervention. The main endpoint was delirium occurrence. Secondary endpoints were agitation-related adverse events and mortality. RESULTS: We included 18 studies comprising 8001 mechanically ventilated patients. Different sedation depths were not associated with the occurrence of delirium (OR = 1.00, 95%CI: 0.64–1.58, P = 0.993). Among the 18 enrolled studies, this finding was not confounded by the dosage of benzodiazepines (OR = 0.96, 95%CI: 0.79–1.17, P = 0.717) in eight randomized controlled trials(RCTs) or the patients’ disease severity(OR 0.95, 95%CI: 0.79–1.13, P = 0.548) in 10 RCTs. However, contrasting results were found in non-RCTs. The deeper sedation group had a significantly increased risk for death(OR = 1.82, 95% CI: 1.23–2.69, P = 0.003), whereas lighter sedation seemed a potential risk for agitation-related adverse events (OR = 0.61, 95%CI: 0.45–0.84, P = 0.002). CONCLUSIONS: It is inconclusive whether significantly different sedation depths would change the risk of delirium in adult mechanically ventilated patients. TRIAL REGISTRATION NUMBER: The study was registered in PROSPERO(http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42019145276.