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Pharmacologic Agents for the Prevention and Treatment of Delirium in Patients Undergoing Cardiac Surgery: Systematic Review and Metaanalysis*

Mu, Jing Lan MMed; Lee, Anna PhD, MPH; Joynt, Gavin M. MBBCh, FCICM

doi: 10.1097/CCM.0000000000000673
Review Articles

Objectives: Postcardiac surgery delirium is associated with increased risks of morbidity, cognitive decline, poor health-related quality of life and mortality, and higher healthcare costs. We performed a systematic review of randomized controlled trials to examine the effect of pharmacologic agents for the prevention and the treatment of delirium after cardiac surgery.

Data Sources: Electronic search on PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, ISI Web of Science, and CINAHL up to December 2013.

Study Selection: Randomized controlled trials of pharmacologic agents used for the prevention and the treatment of delirium after emergency or elective cardiac surgery in adults.

Data Extraction: We extracted data on patient population, pharmacologic agents, delirium characteristics, rescue treatment, length of stays in the ICU and hospital, and mortality. For each trial, we assessed the risk of bias domains and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.

Data Synthesis: Of the 13 studies (10 prevention and three treatment) involving 5,848 patients, one multicentered randomized controlled trial on prophylactic dexamethasone made up 77% of the total sample size. The use of pharmacologic agents (dexamethasone, rivastigmine, risperidone, ketamine, dexmedetomidine, propofol, and clonidine) reduced the risk of delirium (relative risk, 0.57; 95% CI, 0.40–0.80) with quality of evidence rated as moderate. There was high quality of evidence for no increased risk of mortality (relative risk, 0.89; 95% CI, 0.57–1.38) associated with the use of prophylactic pharmacologic agents. Metaanalysis of treatment trials was not undertaken because of high heterogeneity. In two small trials (total number of patients = 133), haloperidol did not appear to be effective in treating delirium.

Conclusions: Moderate to high-quality evidence supports the use of pharmacologic agents for the prevention of delirium, but results are based largely on one randomized controlled trial. The evidence for treating postcardiac surgery delirium with pharmacologic agents is inconclusive.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.

* See also p. 256.

Drs. Lee and Joynt conceived the study. Dr. Lee coordinated the review, screened retrieved articles, appraised the quality of articles, extracted the data from articles, wrote to authors, checked data, performed statistical analysis in STATA, wrote initial draft of article, and is guarantor for the review. Dr. Mu undertook electronic database searches, organized retrieval of articles, screened retrieval articles against inclusion criteria, appraised the quality of articles, extracted the data from articles, entered data and performed metaanalyses in Review Manager, and performed previous work that was the foundation of the present study. Dr. Joynt helped resolved disagreements during the data extraction process and made critical revisions of the article for important intellectual content. All authors interpreted the data, helped revised the article, read and approved the final article.

The work was performed at the Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.

Supported, in part, by a grant from the Research Grants Council of the HKSAR, China (Project reference: CUHK469113).

Part of this work was presented at the Australian and New Zealand Intensive Care Society/Australian College of Critical Care Nurses Annual Scientific Meeting, Hobart, Australia, October 17–19, 2013.

Drs. Lee, Mu, and Joynt received support for article research from the Research Grants Council of the HKSAR, China (Project reference: CUHK469113). Their institutions received grant support from the Research Grants Council of the HKSAR, China (Project reference: CUHK469113). Dr. Mu’s institution received support for travel from The Chinese University of Hong Kong.

For information regarding this article, E-mail: annalee@cuhk.edu.hk

© 2015 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins