We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention.
BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction that may contribute to postoperative complications. Preventing this reaction with steroids may improve outcomes. We performed a systematic review to evaluate the impact of prophylactic steroids on clinical outcomes in patients undergoing on-pump cardiac surgery.
METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL for randomised controlled trials (RCTs) comparing perioperative corticosteroid administration with a control group in adults undergoing CPB. Outcomes of interest included mortality, myocardial infarction, and new onset atrial fibrillation. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS: Fifty-six RCTs published between 1977 and 2015 were included in this meta-analysis. Mortality was not significantly different between groups [3.0% (215/7258 patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group; relative risk (RR), 0.85; 95% confidence interval (CI), 0.71-1.01; P=0.07; I
CONCLUSIONS: After randomising 16 013 patients, steroid administration at the time of cardiac surgery had an unclear impact on mortality, increased the risk of myocardial injury, and the impact on atrial fibrillation should be viewed with caution given that large trials showed no effect.
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.
STUDY OBJECTIVE: To evaluate the effect of steroid administration on myocardial infarction (MI), stroke, renal insufficiency, death, intensive care (ICU) length of stay (LOS) and hospital LOS of patients undergoing cardiopulmonary bypass (CPB).
DESIGN: Meta-analysis of parallel randomized controlled trials.
SETTING: University hospital.
MEAUREMENTS: A search was conducted in PubMed, EMBASE, MEDLINE(R) and the Cochrane Central Register of Controlled Trials of studies on adults undergoing surgery with CPB who received steroid administration. Effect size (risk ratio or mean difference) for MI, stroke, renal insufficiency, death, ICU LOS, and hospital LOS were evaluated.
MAIN RESULTS: 48 RCTs published between 1977 and 2012 were retained for analysis. Steroids had no effect on the MI risk ratio (RR) 0.91 (95% confidence interval [CI] 0.63, 1.32); death at 30 days RR 0.84 (0.59, 1.20); stroke RR 0.92 (0.60, 1.42) or renal insufficiency RR 0.83 (0.52, 1.32). Administration of steroids reduced ICU LOS (P = 0.00001; I(2) 87.5%) and hospital LOS (P = 0.03; I(2) 81.1%). Metaregressions showed that duration of steroid administration was correlated with the reduction in ICU LOS (P = 0.0004) and hospital LOS (P < 0.00001).
CONCLUSIONS: Increasing the duration of steroid administration may reduce ICU and hospital LOS greater than increasing the dose.
AIMS: cardiopulmonary bypass and cardiac surgery are associated with a significant systemic inflammatory response that has been suggested playing a causative role in the development of perioperative atrial fibrillation (POAF). The goal of this meta-analysis was to determine the efficacy of glucocorticoid prophylaxis in preventing POAF, or length of intensive care unite (ICU) or hospital stay.
METHODS: A systematic electronic database literature search of Cochrane controlled trials register (2013, issue 4) and MEDLINE (1966 to April, 2013) was conducted using specific search terms for all relevant articles. Including criteria were: randomized controlled clinical trials, participants were adults (≥18 years of age) undergoing cardiac surgery, evaluated glucocorticoid prophylaxis in cardiac surgery with adequately reported data on incidence of POAF, or length of ICU or hospital stay.
RESULTS: Forty-two randomized controlled trials involving 7621 participants were included in the meta-analysis. Overall, glucocorticoids prophylaxis significantly lowered participants' risk of developing POAF (Relative Risk [RR] 0.77; 95% confidence interval [CI] 0.66-0.90), P < 0.01), reduced length of ICU stay by 0.25 day (95% CI -0.40 to -0.10, P < 0.01). Glucocorticoid prophylaxis in cardiac surgery was not associated with increased all-cause of infection (RR 0.68; 95% CI 0.58-0.78, P < 0.01) and mortality (RR 0.75; 95% CI 0.52-1.08, P = 0.12).
CONCLUSIONS: Pooled evidence suggests that glucocorticoid prophylaxis may reduce the incidence of POAF. The beneficial effect on POAF is associated with reduced length of ICU and hospital stay, and infection rate.
We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention.
