Randomized ICU trials do not demonstrate an association between interventions that reduce delirium duration and short-term mortality: a systematic review and meta-analysis

• Published in: Critical care medicine Vol. 42; no. 6; p. 1442
• Main Authors: Al-Qadheeb, Nada S, Balk, Ethan M, Fraser, Gilles L, Skrobik, Yoanna, Riker, Richard R, Kress, John P, Whitehead, Shawn, Devlin, John W
• Format: Journal Article
• Language: English
• Published: United States 01.06.2014
• Subjects: Delirium - mortality; Delirium - prevention & control; Delirium - therapy; Intensive Care Units; Time Factors
• ISSN: 1530-0293
• DOI: 10.1097/CCM.0000000000000224

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. We searched CINHAHL, EMBASE, MEDLINE, and the Cochrane databases from 2001 to 2012. 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). 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. 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). 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.