Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium

Boogaard, Mark van den; Slooter, Arjen J. C.; Brüggemann, Roger J. M.; Schoonhoven, Lisette; Beishuizen, Albertus; Vermeijden, Wytze J.; Pretorius, Danie; Koning, Jan de; Simons, Koen S.; Dennesen, Paul J. W.; Voort, Peter H. J. van der; Houterman, Saskia; Hoeven, Johannes G. van der; Pickkers, Peter; Woude, Margaretha C. E. van der; Besselink, Anna; Hofstra, Lieuwe S.; Spronk, Peter E.; Bergh, W. van den; Donker, Dirk W.; Fuchs, Malaika; Karakus, Attila; Koeman, Mirelle; Duijnhoven, M. van; Hannink, Gerjon

doi:10.1001/jama.2018.0160

Cited by 215 publications

(132 citation statements)

References 33 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…Single, randomized studies of adults who were admitted to the ICU for postoperative care were reviewed for haloperidol (366); the atypical antipsychotic, risperidone (367); and dexmedetomidine (368). Each study reported a significant reduction in delirium incidence favoring the pharmacologic agent: scheduled IV haloperidol (n = 457) after noncardiac surgery (RR, 0.66; 95% CI, 0.45-0.97; low quality) ( evidence profile, found that administration of low-dose IV haloperidol in the ICU until delirium developed did not help prevent delirium or affect 90-day survival (369). Another suggested that nocturnal administration of low-dose dexmedetomidine in critically ill adults with APACHE-II scores of 22 (sd, ± 7.8) was associated with a significantly greater proportion of patients who remained delirium free (80% vs 54%; p = 0.008) during their ICU stay (370).…”

Section: Preventionmentioning

confidence: 99%

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Devlin

Skrobik

Gélinas

et al. 2018

Critical Care Medicine

Self Cite

2,321

2,938

View full text Add to dashboard Cite

We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

show abstract

Section: Preventionmentioning

confidence: 99%

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Devlin

Skrobik

Gélinas

et al. 2018

Critical Care Medicine

Self Cite

2,321

2,938

View full text Add to dashboard Cite

show abstract

“…36 The patient population in that study was not as critically ill as expected in a traditional MICU or SICU. The high severity of illness, as seen in our study and the aforementioned ICU trials, [31][32][33] may render it difficult to control delirium symptoms with a single agent without managing other mechanistic pathways involved in delirium pathophysiology. Even though we focused on three neurotransmitter pathways (ie, dopaminergic, cholinergic, and GABA), we still could not reduce delirium duration and severity.…”

Section: Discussionmentioning

confidence: 83%

“…The aforementioned trials tested haloperidol as a sole intervention compared to placebo or another antipsychotic. [31][32][33] Rather than focusing on just the dopaminergic pathway, we targeted two additional neurotransmitter imbalances in the cholinergic and the GABA systems. As delirium is a complex pathophysiological process, we hypothesized that a combined approach might be better suited to reduce delirium.…”

Section: Discussionmentioning

confidence: 99%

“…The PMD bundle did not decrease the risk of death and lengths of ICU and hospital stay, nor did it reduce the duration of mechanical ventilation, findings similar to other pharmacologic delirium trials in the ICU setting. [31][32][33] To improve these outcomes, system-wide changes could be required in addition to the pharmacological approaches to delirium. Programs employing six or more implementation strategies targeting delirium assessment, prevention, and treatment with integration of the pain, agitation, and delirium guidelines 22 or the ABCDE bundle 34 (Awakening and Breathing coordination, Choice of sedation, Delirium monitoring, and Early Mobility) may be better suited to improve ICU length of stay.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological Management of Delirium in the Intensive Care Unit: A Randomized Pragmatic Clinical Trial

Khan

Perkins

Campbell

et al. 2019

J American Geriatrics Society

View full text Add to dashboard Cite

Background/Objective: Delirium in the intensive care units (ICU) is prevalent with both delirium duration and delirium severity associated with adverse outcomes. We designed a pragmatic trial to test the efficacy of a pharmacological management of delirium (PMD) bundle in improving delirium/coma free days and reducing delirium severity among ICU patients. Design: A randomized pragmatic clinical trial. Setting: Medical, surgical, and progressive ICUs of three tertiary care hospitals. Participants: 351 critically ill patients. Intervention: A multi-component PMD bundle consisting of reducing the exposure to 20 definite anticholinergic medications and benzodiazepines, and prescribing low-dose haloperidol. Measurements: The primary outcomes were delirium/coma free days measured through Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU) and delirium severity measured through Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7. Secondary outcomes were in-hospital and post-hospital discharge 30-day mortality, ICU and hospital lengths of stay, and delirium-related hospital complications. Results: We randomized 351 critically ill delirious patients [mean age=59.3 years (SD 16.9); 52% female, 42% African-Americans] to receive the PMD bundle or usual care. There were no significant differences in median delirium/coma free days at day 8 [PMD: 4 (IQR 2–7) days versus usual care 5 (1–7), p=0.888] or at day 30 [26 (IQR 19–29) days versus 26 (14–29), p=0.991]. There were no significant differences for decrease in delirium severity at day 8, but at hospital discharge, the intervention group showed a greater reduction in delirium severity [PMD: mean decrease in CAM-ICU-7 score=3.2 (SD 3.3) versus usual care: mean decrease=2.5 (SD 3.2); p=0.046]. No differences were observed between groups for ICU and hospital lengths of stay, mortality and delirium-related hospital complications. Similar results were observed when analyses were limited to patients ≥ 65 and ≥ 75 years. Conclusion and Relevance: Implementing the PMD Bundle in the ICU did not reduce delirium duration or severity among critically ill patients. Trial Registration: clinicaltrials.gov Identifier:

show abstract

“…Our results were similar to those of the Hope-ICU 41 and (REDUCE) trials. 42 Both compared haloperidol with placebo in traditional medical and surgical ICU populations and used delirium-and coma-free days as one of the outcomes. They tested a slightly higher dose of haloperidol (Hope-ICU: 2.4 mg every 8 hours, REDUCE: 2 mg 3 times daily) than the 0.5 mg 3 times daily that we used.…”

Section: Discussionmentioning

confidence: 99%

Preventing Postoperative Delirium After Major Noncardiac Thoracic Surgery—A Randomized Clinical Trial

Khan

Perkins

Campbell

et al. 2018

J American Geriatrics Society

View full text Add to dashboard Cite

Objectives To assess the efficacy of haloperidol in reducing postoperative delirium in individuals undergoing thoracic surgery. Design Randomized double‐blind placebo‐controlled trial. Setting Surgical intensive care unit (ICU) of tertiary care center. Participants Individuals undergoing thoracic surgery (N=135). Intervention Low‐dose intravenous haloperidol (0.5 mg three times daily for a total of 11 doses) administered postoperatively. Measurements The primary outcome was delirium incidence during hospitalization. Secondary outcomes were time to delirium, delirium duration, delirium severity, and ICU and hospital length of stay. Delirium was assessed using the Confusion Assessment Method for the ICU and delirium severity using the Delirium Rating Scale‐Revised. Results Sixty‐eight participants were randomized to receive haloperidol and 67 placebo. No significant differences were observed between those receiving haloperidol and those receiving placebo in incident delirium (n=15 (22.1%) vs n=19 (28.4%); p = .43), time to delirium (p = .43), delirium duration (median 1 day, interquartile range (IQR) 1‐2 days vs median 1 day, IQR 1‐2 days; p = .71), delirium severity, ICU length of stay (median 2.2 days, IQR 1–3.3 days vs median 2.3 days, IQR 1‐4 days; p = .29), or hospital length of stay (median 10 days, IQR 8–11.5 days vs median 10 days, IQR 8‐12 days; p = .41). In the esophagectomy subgroup (n = 84), the haloperidol group was less likely to experience incident delirium (n=10 (23.8%) vs n=17 (40.5%); p = .16). There were no differences in time to delirium (p = .14), delirium duration (median 1 day, IQR 1‐2 days vs median 1 day, IQR 1‐2 days; p = .71), delirium severity, or hospital length of stay (median 11 days, IQR 10‐12 days vs median days 11, IQR 10‐15 days; p = .26). ICU length of stay was significantly shorter in the haloperidol group (median 2.8 days, IQR 1.1–3.8 days vs median 3.1 days, IQR 2.1–5.1 days; p = .03). Safety events were comparable between the groups. Conclusion Low‐dose postoperative haloperidol did not reduce delirium in individuals undergoing thoracic surgery but may be efficacious in those undergoing esophagectomy. J Am Geriatr Soc 66:2289–2297, 2018.

show abstract

Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium

Abstract: clinicaltrials.gov Identifier: NCT01785290.

Cited by 215 publications

References 33 publications

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Pharmacological Management of Delirium in the Intensive Care Unit: A Randomized Pragmatic Clinical Trial

Preventing Postoperative Delirium After Major Noncardiac Thoracic Surgery—A Randomized Clinical Trial

Contact Info

Product

Resources

About