Deprescribing in the Pharmacologic Management of Delirium: A Randomized Trial in the Intensive Care Unit

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

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Abstract

Objective: Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. Design: Multisite randomized clinical trial. Setting: ICUs of three large hospitals. Participants: Two hundred adults aged 18 years or older and admitted to an ICU with delirium, according to the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy, or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. Measurements: Primary outcomes were delirium duration measured by the CAM-ICU and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. Results: Participants had a mean age of 61.8 (SD = 14.3) years, 59% were female, and 52% were African American, with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (P =.219) or benzodiazepines (P =.566), the median total anticholinergic score (P =.282), or the median total benzodiazepine dose in lorazepam equivalents (P =.501). Neither median delirium/coma-free days (P =.361) nor median change in delirium severity scores (P =.582 for DRS-R-98; P =.333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. Conclusions: When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes.

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

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Delirium
Intensive Care Units
Cholinergic Antagonists
Confusion
Benzodiazepines
Haloperidol
Deprescriptions
Lorazepam
Mortality
Coma
Pharmacists
African Americans
Epilepsy
Randomized Controlled Trials
Stroke
Alcohols
Pregnancy

Keywords

  • anticholinergic
  • benzodiazepine
  • delirium
  • deprescribing

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

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

In: Journal of the American Geriatrics Society, 01.01.2019.

Research output: Contribution to journalArticle

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T2 - A Randomized Trial in the Intensive Care Unit

AU - Campbell, Noll L.

AU - Perkins, Anthony J.

AU - Khan, Babar

AU - Gao, Sujuan

AU - Farber, Mark O.

AU - Khan, Sikandar

AU - Wang, Sophia

AU - Boustani, Malaz

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N2 - Objective: Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. Design: Multisite randomized clinical trial. Setting: ICUs of three large hospitals. Participants: Two hundred adults aged 18 years or older and admitted to an ICU with delirium, according to the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy, or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. Measurements: Primary outcomes were delirium duration measured by the CAM-ICU and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. Results: Participants had a mean age of 61.8 (SD = 14.3) years, 59% were female, and 52% were African American, with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (P =.219) or benzodiazepines (P =.566), the median total anticholinergic score (P =.282), or the median total benzodiazepine dose in lorazepam equivalents (P =.501). Neither median delirium/coma-free days (P =.361) nor median change in delirium severity scores (P =.582 for DRS-R-98; P =.333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. Conclusions: When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes.

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