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

Mu, Jing; Lee, Anna; Joynt, Gavin M.

doi:10.1097/ccm.0000000000000673

Cited by 52 publications

(22 citation statements)

References 37 publications

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“…The results of our investigation differ from controlled studies where the administration of low-dose antipsychotic therapy to surgical patients has been shown to reduce delirium prevalence, delay its occurrence and/or shorten its duration (10-16). While some of the patients in these investigations required short-term, post-operative ICU care (14-16), very few would be considered to be deemed to be critically ill. Risk factors for delirium that are different between elective surgery patients and the critically ill may help explain the lack of benefit we observed with the use of haloperidol (17, 18, 33).…”

Section: Discussioncontrasting

confidence: 95%

“…While some of the patients in these investigations required short-term, post-operative ICU care (14-16), very few would be considered to be deemed to be critically ill. Risk factors for delirium that are different between elective surgery patients and the critically ill may help explain the lack of benefit we observed with the use of haloperidol (17, 18, 33). Critically ill patients may be at greater risk for experiencing haloperidol-associated adverse effects (20, 21, 34).…”

Section: Discussionmentioning

confidence: 99%

“…Perioperative use of low-dose antipsychotic therapy in non-critically ill patients undergoing elective major surgery, where a short post-operative ICU admission is sometimes required, has been shown to reduce delirium burden (i.e., delirium incidence, duration or both) (10-16). However the results of these investigations cannot be extrapolated to the critically ill given the different mechanisms, risk factors and outcomes of delirium that exist between the ICU and non-ICU populations (9, 17, 18).…”

Section: Introductionmentioning

confidence: 99%

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Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol

Al-Qadheeb

Skrobik

Schumaker

et al. 2016

Critical Care Medicine

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Objective To compare the efficacy and safety of scheduled low-dose, haloperidol vs. placebo for the prevention of delirium [Intensive Care Delirium Screening Checklist (ICDSC) ≥ 4)] administered to critically ill adults with subsyndromal delirium (ICDSC = 1-3). Design Randomized, double-blind, placebo-controlled trial. Setting Three 10-bed ICUs (2 medical; 1 surgical) at an academic medical center in the U.S. Patients Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery or requiring deep sedation. Interventions Patients were randomly assigned to receive intravenous haloperidol 1 mg or placebo every six hours until either delirium (ICDSC ≥ 4 with psychiatric confirmation), therapy ≥ 10 days or ICU discharge occurred. Measurements and Main Results Baseline characteristics were similar between the haloperidol (n=34) and placebo (n=34) groups. A similar number of patients given haloperidol [12/34 (35%)] and placebo [8/34 (23%)] patients developed delirium (p=0.29). Haloperidol use reduced the hours per study day spent agitated (SAS ≥ 5) (p=0.008), but did not influence the proportion of 12-hour ICU shifts patients’ spent alive without coma (SAS ≤ 2) or delirium (p=0.36), the time to first delirium occurrence (p=0.22) nor delirium duration (p=0.26). Days of mechanical ventilation (p=0.80), ICU mortality (p=0.55) and ICU patient disposition (p=0.22) were similar in the two groups. The proportion of patients who developed QTc-interval prolongation (p=0.16), extrapyramidal symptoms (p=0.31), excessive sedation (p=0.31) or new-onset hypotension (p=1.0) that resulted in study drug discontinuation was comparable between the two groups. Conclusions Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium.

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Section: Discussioncontrasting

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol

Al-Qadheeb

Skrobik

Schumaker

et al. 2016

Critical Care Medicine

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“…Some studies have shown that antipsychotics shorten the duration of delirium; others have shown that antipsychotics are associated with transition to delirium(35,38,39). There is research that indicates that corticosteroids may increase the risk of delirium in geriatric patients, and additional research that suggests that corticosteroids are not harmful, and may be protective against the development of delirium after cardiopulmonary bypass (40–42). It is likely that although the final common pathway leading to delirium may be the same (alteration in neurotransmission, which results in an acute and fluctuating change in awareness and cognition), there are many disparate etiologies that can trigger the delirium cascade(43).…”

Section: Discussionmentioning

confidence: 99%

Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium*

Traube

Silver

Gerber

et al. 2017

Critical Care Medicine

267

254

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Objective Delirium occurs frequently in adults, and is an independent predictor of mortality. However, the epidemiology and outcomes of pediatric delirium are not well-characterized. The primary objectives of this study were to describe the incidence of delirium in critically ill children, its duration, associated risk factors, and effect on in-hospital outcomes, including mortality. Secondary objectives included determination of delirium subtype, and effect of delirium on duration of mechanical ventilation (MV), and length of hospital stay (LOS). Design Prospective longitudinal cohort study. Setting Urban academic tertiary care pediatric intensive care unit (PICU). Patients All consecutive admissions from September 2014 through August 2015. Intervention Children were screened for delirium twice daily throughout their ICU stay. Measurements and Main Results Of 1547 consecutive patients, delirium was diagnosed in 267 (17%), and lasted a median of two days (IQR 1,5). Seventy-eight percent of children with delirium developed it within the first three PICU days. Most cases of delirium were of the hypoactive (46%) and mixed (45%) subtypes; only 8% of delirium episodes were characterized as hyperactive delirium. In multivariable analysis, independent predictors of delirium included age ≤2 years, developmental delay, severity of illness, prior coma, mechanical ventilation, and receipt of benzodiazepines and anticholinergics. PICU LOS was increased in children with delirium (adjusted relative LOS 2.3, CI= 2.1, 2.5, p<0.001), as was duration of MV (median 4 vs. 1 day, p<0.001). Delirium was a strong and independent predictor of mortality (adjusted OR 4.39, CI= 1.96–9.99, p<0.001). Conclusions Delirium occurs frequently in critically ill children and is independently associated with mortality. Some in-hospital risk factors for delirium development are modifiable. Interventional studies are needed to determine best practices to limit delirium exposure in at-risk children.

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“…Furthermore, if researchers perform placebo controlled intervention trials, the incidence in the placebo group could be compared with that of the meta-analysis to ensure the placebo group had the expected incidence. The incidence could also be used to help researchers perform power calculations for number of subjects needed in trials 12. Finally, the incidence of postoperative delirium varies depending on the characteristics of patients and type of surgery 6–9.…”

Section: Introductionmentioning

confidence: 99%

The incidence of delirium after cardiac surgery in the elderly: protocol for a systematic review and meta-analysis

et al. 2017

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IntroductionDelirium is one of the most common complications after cardiac surgery in the elderly. Future studies aimed at preventing postoperative delirium will need an accurate estimate of incidence. However, there are no available systematic reviews on the incidence, and reports of incidence of postoperative delirium after a cardiac operation vary widely with significant heterogeneity. Therefore, we aim to perform a systematic review and meta-analysis to determine the most accurate incidence possible of postoperative delirium in individuals aged >65 years after cardiac surgery.Methods and analysesWe will undertake a comprehensive literature search among PubMed, EMBASE, the Cochrane Library, PsycINFO and CINAHL, from their inception to January 2017. Prospective cohort and cross sectional studies that described the incidence of delirium will be eligible for inclusion. The primary outcome will be the incidence of delirium. Risk of bias and methodological quality for the included studies will be assessed using a risk of bias tool for prevalence studies and the Cochrane guidelines. Heterogeneity of the estimates across studies will be assessed. Incidence data will be pooled by selective or emergency surgery. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).Ethics and disseminationThis proposed systematic review and meta-analysis is based on published data, and thus there is no requirement for ethics approval. The study will provide an up to date and accurate incidence of postoperative delirium among the older population after cardiac surgery, which is necessary for future research in this area. The findings of this study will be presented at conferences and disseminated through publication in a peer reviewed journal.Trial registration numberCRD42016047773.

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

Abstract: 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.

Cited by 52 publications

References 37 publications

Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol

Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol

Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium*

The incidence of delirium after cardiac surgery in the elderly: protocol for a systematic review and meta-analysis

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