Dataset Information

Donepezil treatment is associated with improved outcomes in critically ill dementia patients via a reduction in delirium.

ABSTRACT:

Introduction

During hospital admissions, patients with dementia are at risk for developing delirium, an acute state of brain failure associated with significant morbidity. There are currently no pharmacologic tools to treat or prevent delirium. Decreased cholinergic signaling plays a role in the pathophysiology of both disorders. Whether enhanced pre-hospital cholinergic signaling in patients with dementia improves outcomes during critical illness remains unknown.

Methods

We utilized the Medical Information Mart for Intensive Care III (MIMIC-III) database to determine whether pre-hospital donepezil use was associated with improved outcomes during critical illness in dementia patients.

Results

We identified 2734 subjects with dementia admitted to the intensive care unit (ICU; 447 received donepezil). After adjusting for confounders, patients with dementia who were receiving donepezil had a significantly reduced in-hospital and 90-day mortality, ICU length of stay, and duration of mechanical ventilation. Donepezil use was associated with, and its benefit was mediated by, reduced delirium.

Discussion

Patients with dementia who are treated with donepezil have improved outcomes during critical illness and reductions in delirium.

Highlights

No pharmacologic treatments exist to reduce delirium in patients with dementia. Donepezil improves outcomes during critical illness in patients with dementia. Improved outcomes are mediated by a reduction in hospital delirium. Future studies in patients with dementia should prospectively evaluate donepezil in the prevention of delirium.

SUBMITTER: Lieberman OJ

PROVIDER: S-EPMC10483393 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Donepezil treatment is associated with improved outcomes in critically ill dementia patients via a reduction in delirium.

Lieberman Ori J OJ Lee Seonjoo S Zabinski Jeffrey J

Alzheimer's & dementia : the journal of the Alzheimer's Association 20221011 5

<h4>Introduction</h4>During hospital admissions, patients with dementia are at risk for developing delirium, an acute state of brain failure associated with significant morbidity. There are currently no pharmacologic tools to treat or prevent delirium. Decreased cholinergic signaling plays a role in the pathophysiology of both disorders. Whether enhanced pre-hospital cholinergic signaling in patients with dementia improves outcomes during critical illness remains unknown.<h4>Methods</h4>We utili ...[more]

PMID: 36218161

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Project description:ObjectivesHaloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality.DesignPost hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial.SettingFourteen Dutch ICUs between July 2013 and December 2016.PatientsOne-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 2 days.InterventionsPatients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg tid (up to 5 mg tid per delirium symptoms) was administered at clinician discretion.Measurements and main resultsPatients were evaluated tid for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2-7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0-3.8 mg] daily) for 6 days (3-11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91-0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96-0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium haloperidol exposure, and haloperidol treatment protocol adherence.ConclusionsTreatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results.

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Project description:OBJECTIVES:Catatonia, a condition characterized by motor, behavioral, and emotional changes, can occur during critical illness and appear as clinically similar to delirium, yet its management differs from delirium. Traditional criteria for medical catatonia preclude its diagnosis in delirium. Our objective in this investigation was to understand the overlap and relationship between delirium and catatonia in ICU patients and determine diagnostic thresholds for catatonia. DESIGN:Convenience cohort, nested within two ongoing randomized trials. SETTING:Single academic medical center in Nashville, TN. PATIENTS:We enrolled 136 critically ill patients on mechanical ventilation and/or vasopressors, randomized to two usual care sedation regimens. MEASUREMENTS AND MAIN RESULTS:Patients were assessed for delirium and catatonia by independent and masked personnel using Confusion Assessment Method for the ICU and the Bush Francis Catatonia Rating Scale mapped to Diagnostic Statistical Manual 5 criterion A for catatonia. Of 136 patients, 58 patients (43%) had only delirium, four (3%) had only catatonia, 42 (31%) had both, and 32 (24%) had neither. In a logistic regression model, more catatonia signs were associated with greater odds of having delirium. For example, patient assessments with greater than or equal to three Diagnostic Statistical Manual 5 symptoms (75th percentile) had, on average, 27.8 times the odds (interquartile range, 12.7-60.6) of having delirium compared with patient assessments with zero Diagnostic Statistical Manual 5 criteria (25th percentile) present (p < 0.001). A cut-off of greater than or equal to 4 Bush Francis Catatonia Screening Instrument items was both sensitive (91%; 95% CI, 82.9-95.3) and specific (91%; 95% CI, 87.6-92.9) for Diagnostic Statistical Manual 5 catatonia. CONCLUSIONS:Given that about one in three patients had both catatonia and delirium, these data prompt reconsideration of Diagnostic Statistical Manual 5 criteria for "Catatonic Disorder Due to Another Medical Condition" that preclude diagnosing catatonia in the presence of delirium.

Dataset Information

Donepezil treatment is associated with improved outcomes in critically ill dementia patients via a reduction in delirium.

Introduction

Methods

Results

Discussion

Highlights

Publications

Donepezil treatment is associated with improved outcomes in critically ill dementia patients via a reduction in delirium.

Similar Datasets

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