Meta-analysis associates deep sedation with increased delirium and mortality in ICU patients

BackgroundDelirium and poor clinical prognoses are prevalent among ICU patients, particularly those requiring mechanical ventilation. While sedation is a cornerstone of intensive care, the impact of its depth remains controversial; deep sedation is often linked to adverse outcomes, whereas light sedation may improve recovery trajectories. We conducted a systematic review and meta-analysis to clarify the association between sedation depth and delirium incidence, mortality, and ICU length of stay (LOS).MethodsFollowing PRISMA 2020 guidelines and PROSPERO registration (CRD420251054377), we searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) and cohort studies published through June 17, 2025. Two reviewers independently performed data extraction and quality assessment using RoB 2 for RCTs and the Newcastle-Ottawa Scale (NOS) or ROBINS-I for non-randomized studies. Evidence quality was evaluated using the GRADE framework.ResultsEleven studies (6 RCTs, 5 cohorts) involving 3,466 patients were included. Meta-analysis using a fixed-effects model demonstrated that deep sedation was significantly associated with a higher incidence of delirium (OR: 1.34; 95% CI: 1.15–1.57; P = 0.0001; I2 = 18%). Deep sedation was also significantly linked to increased mortality (OR: 1.71; 95% CI: 1.32–2.21; P < 0.0001; I2 = 1%) and prolonged ICU LOS (MD: 1.17 days; 95% CI: 0.54–1.81; P = 0.0003; I2 = 23%). A secondary analysis of two studies comparing dexmedetomidine to other sedatives was limited by the small number of included studies and low statistical power, such that current evidence remains insufficient to draw a definitive conclusion regarding its effect on delirium incidence (OR: 0.93; 95% CI: 0.57–1.51; P = 0.77). GRADE assessment rated the overall quality of evidence for primary outcomes as Moderate, downgraded primarily due to residual confounding in cohort studies.ConclusionDeep sedation is significantly associated with an increased risk of delirium, higher mortality, and extended ICU stays. While these associations are consistent across study designs, clinicians should account for the multifactorial influences on these outcomes. Implementing sedation protocols that prioritize lighter sedation depth may be associated with improved ICU patient prognoses.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251054377, identifier CRD420251054377.