Randomized ICU Trials Do Not Demonstrate an Association Between Interventions That Reduce Delirium Duration and Short-Term Mortality: A Systematic Review and Meta-Analysis

Objectives: We reviewed randomized trials of adult ICU patients of interventions hypothesized to reduce delirium burden to determine whether interventions that are more effective at reducing delirium duration are associated with a reduction in short-term mortality. Data Sources: We searched CINHAHL, EMBASE, MEDLINE, and the Cochrane databases from 2001 to 2012. Study Selection: Citations were screened for randomized trials that enrolled critically ill adults, evaluated delirium at least daily, compared a drug or nondrug intervention hypothesized to reduce delirium burden with standard care (or control), and reported delirium duration and/or short-term mortality ( 45 d). Data Extraction: In duplicate, we abstracted trial characteristics and results and evaluated quality using the Cochrane risk of bias tool. We performed random effects model meta-analyses and meta-regressions. Data Synthesis: We included 17 trials enrolling 2,849 patients which evaluated a pharmacologic intervention (n = 13) (dexmedetomidine [n = 6], an antipsychotic [n = 4], rivastigmine [n = 2], and clonidine [n = 1]), a multimodal intervention (n = 2) (spontaneous awakening [n = 2]), or a nonpharmacologic intervention (n = 2) (early mobilization [n = 1] and increased perfusion [n = 1]). Overall, average delirium duration was lower in the intervention groups (difference = -0.64 d; 95% CI, -1.15 to -0.13; p = 0.01) being reduced by more than or equal to 3 days in three studies, 0.1 to less than 3 days in six studies, 0 day in seven studies, and less than 0 day in one study. Across interventions, for 13 studies where short-term mortality was reported, short-term mortality was not reduced (risk ratio = 0.90; 95% CI, 0.76-1.06; p = 0.19). Across 13 studies that reported mortality, meta-regression revealed that delirium duration was not associated with reduced short-term mortality (p = 0.11). Conclusions: A review of current evidence fails to support that ICU interventions that reduce delirium duration reduce short-term mortality. Larger controlled studies are needed to establish this relationship.