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

Babar Khan, Anthony J. Perkins, Noll L. Campbell, Sujuan Gao, Mark O. Farber, Sophia Wang, Sikandar H. Khan, Ben L. Zarzaur, Malaz Boustani

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND/OBJECTIVE: Delirium in the intensive care units (ICUs) 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: A total of 351 critically ill patients. INTERVENTION: A multicomponent 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 the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU), and delirium severity, measured through Delirium Rating Scale-Revised-98 and the CAM-ICU-7. Secondary outcomes were in-hospital and posthospital 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 years]; 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 vs usual care = 4 [interquartile range {IQR} = 2-7] days vs 5 [IQR = 1–7] days; P =.888) or at day 30 (PMD vs usual care = 26 [IQR 19-29] days vs 26 [IQR, 14–29] days; P =.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 (mean decrease in CAM-ICU-7 score for PMD vs usual care = 3.2 [SD = 3.3] vs 2.5 [SD = 3.2]; P =.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 years or older and 75 years or older. 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: NCT00842608.

Original languageEnglish (US)
JournalJournal of the American Geriatrics Society
DOIs
StateAccepted/In press - Jan 1 2019

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Pragmatic Clinical Trials
Delirium
Intensive Care Units
Randomized Controlled Trials
Pharmacology
Confusion
Length of Stay
Coma
Critical Illness

Keywords

  • benzodiazepine
  • delirium
  • haloperidol
  • randomized trial

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

Pharmacological Management of Delirium in the Intensive Care Unit : A Randomized Pragmatic Clinical Trial. / Khan, Babar; Perkins, Anthony J.; Campbell, Noll L.; Gao, Sujuan; Farber, Mark O.; Wang, Sophia; Khan, Sikandar H.; Zarzaur, Ben L.; Boustani, Malaz.

In: Journal of the American Geriatrics Society, 01.01.2019.

Research output: Contribution to journalArticle

Khan, Babar ; Perkins, Anthony J. ; Campbell, Noll L. ; Gao, Sujuan ; Farber, Mark O. ; Wang, Sophia ; Khan, Sikandar H. ; Zarzaur, Ben L. ; Boustani, Malaz. / Pharmacological Management of Delirium in the Intensive Care Unit : A Randomized Pragmatic Clinical Trial. In: Journal of the American Geriatrics Society. 2019.
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AU - Perkins, Anthony J.

AU - Campbell, Noll L.

AU - Gao, Sujuan

AU - Farber, Mark O.

AU - Wang, Sophia

AU - Khan, Sikandar H.

AU - Zarzaur, Ben L.

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N2 - BACKGROUND/OBJECTIVE: Delirium in the intensive care units (ICUs) 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: A total of 351 critically ill patients. INTERVENTION: A multicomponent 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 the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU), and delirium severity, measured through Delirium Rating Scale-Revised-98 and the CAM-ICU-7. Secondary outcomes were in-hospital and posthospital 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 years]; 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 vs usual care = 4 [interquartile range {IQR} = 2-7] days vs 5 [IQR = 1–7] days; P =.888) or at day 30 (PMD vs usual care = 26 [IQR 19-29] days vs 26 [IQR, 14–29] days; P =.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 (mean decrease in CAM-ICU-7 score for PMD vs usual care = 3.2 [SD = 3.3] vs 2.5 [SD = 3.2]; P =.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 years or older and 75 years or older. 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: NCT00842608.

AB - BACKGROUND/OBJECTIVE: Delirium in the intensive care units (ICUs) 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: A total of 351 critically ill patients. INTERVENTION: A multicomponent 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 the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU), and delirium severity, measured through Delirium Rating Scale-Revised-98 and the CAM-ICU-7. Secondary outcomes were in-hospital and posthospital 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 years]; 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 vs usual care = 4 [interquartile range {IQR} = 2-7] days vs 5 [IQR = 1–7] days; P =.888) or at day 30 (PMD vs usual care = 26 [IQR 19-29] days vs 26 [IQR, 14–29] days; P =.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 (mean decrease in CAM-ICU-7 score for PMD vs usual care = 3.2 [SD = 3.3] vs 2.5 [SD = 3.2]; P =.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 years or older and 75 years or older. 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: NCT00842608.

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