Pharmacologic Agents for the Prevention and Treatment of Delirium in Patients Undergoing Cardiac Surgery

Systematic Review and Metaanalysis

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


Crit Care Med. 2015;43(1):194-204. 

In This Article

Abstract and Introduction


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.


Delirium is a syndrome characterized by the acute onset of fluctuating levels of attention, awareness, and cognition.[1] Most ICU healthcare professionals recognize delirium not only as a common and potentially serious problem but also that it is frequently underdiagnosed.[2]

Patients undergoing cardiac surgery have unique characteristics and present special challenges. Dedicated cardiac surgical ICUs are common in the United States, Europe, and Australasia. Patients undergoing cardiac surgery are exposed to specific risk factors for delirium, such as cardiopulmonary bypass and circulatory arrest, and appear at high risk of delirium. The reported incidence varies from 12% to 52%.[3,4] Typically, delirium after cardiac surgery develops on the first to second day after admission to the ICU[3,4] and lasts for 1 to 3 days[4–6] with hypoactive delirium (88%) being the most common subtype.[7]

ICU delirium is reversible but associated with poor patient outcomes, such as a prolonged stay in the ICU and in hospital, higher risk of mortality, slower recovery from cognitive impairment, decreased quality of life, and higher healthcare costs.[3,8,9] Early management of delirium may reduce poor outcomes and may minimize costly treatments for long-term physical and mental disorders.

The most recent 2013 American College of Critical Care medicine guidelines for the management of pain, agitation, and delirium in adult patients in ICU provided no recommendation for using pharmacologic agents for the prevention of delirium.[10] For the treatment of delirium, the guidelines[10] found no evidence to support the use of haloperidol, low-quality evidence to support the use of atypical antipsychotics and recommended against the use of rivastigmine to reduce the duration of delirium. There was no recommendation for the use of dexmedetomidine for the prevention of delirium, but weak evidence to support its use for sedation, as an alternative to benzodiazepines, to reduce the prevalence of delirium.[10]

There are emerging, but not definitive, data evaluating the effectiveness of pharmacologic agents for the management of delirium in the cardiac surgical population.[11–23] Our hypothesis was that pharmacologic agents are effective for the prevention and the treatment of delirium after cardiac surgery. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to address the hypothesis.