Cholinesterase Activity and DeliriUm During Critical Illness Study (CADUCeuS)

Cholinesterase Activity and Delirium During Critical Illness Study

Delirium is a syndrome of acute brain dysfunction involving attention and cognition that affects up to half of older hospitalized patients and 50%-75% of critically ill ICU patients, such that millions of patients worldwide experience this acute threat to their health and well being every year. One-third to half of critical illness survivors struggle with a dementia-like disorder similar in severity to moderate-to-severe traumatic brain injury or Alzheimer's Disease, and the only proven risk factor that is potentially modifiable is delirium in the ICU. Despite the frequency and impact of delirium in the ICU, little is known regarding the biological mechanisms that lead to this form of organ dysfunction during critical illness. A widely held hypothesis proposes that inflammation is regulated by the cholinergic system, and that this interaction plays a pivotal role whether delirium developments in the setting of acute illness. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are enzymes that hydrolyze the neurotransmitter acetylcholine. Changes in the activity of these enzymes, which can be measured in whole blood, reflect altered regulation of circulating acetylcholine. AChE and BuChE activities have promise as both predictors of delirium (when found to be low at admission) and biomarkers of delirium (when low during serial measurement). Neither of these biomarkers, however, have been studied in the ICU setting where delirium risk is the highest. The current investigation, therefore will be the first to determine the validity of circulating AChE and BuChE activities as biomarkers of delirium during critical illness and subsequent cognitive impairment after discharge. This study will measure whole blood AChE and butyrylcholinesterase BuChE activities within the framework of the ICU Delirium and Cognitive Impairment Study Group's ongoing clinical trials in critically ill patients.

Study Overview

• Status: Completed
• Conditions: Delirium; Cognitive Impairment

• Study Type: Observational
• Enrollment (Actual): 279

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study will include all patients in the ICU Delirium and Cognitive Impairment Study Group's ongoing clinical trials over a two-year period of time.

Description

Inclusion Criteria:

• English-speaking adults (>18 years of age) treated for acute respiratory failure (with mechanical ventilation or non-invasive positive pressure ventilation [NIPPV]) and/or shock (with vasopressors) in a medical and/or surgical ICU at Vanderbilt University Medical Center enrolled in an ICU Delirium and Cognitive Impairment Study Group's clinical trials. Exclusion criteria for the parent studies are summarized below. No additional exclusion criteria are required for this investigation.

Exclusion Criteria:

• Expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family or the medical team (e.g., likely withdrawal of life support measures within 24 hours of screening)
• Active substance abuse, psychotic disorder, or homelessness without a secondary contact person (which would make long-term follow-up difficult)
• Blindness or deafness (which would prevent assessment of the study's outcomes)
• Inability to obtain informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium	Confusion Assessment Method for the ICU	During hospital stay until death or hospital discharge, whichever comes first, up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global cognition	Neuropsychological battery	At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activities of daily living	Katz Index of Independence in Activities of Daily Living	At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge
Instrumental activities of daily living	Functional activities questionnaire	At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge
Quality of life and generic health status	EQ-5D	At 3, 6, and/or 12 months after hospital discharge up to 18 months after discharge
Coma	Richmond Agitation Sedation Scale	During hospital stay until death or hospital discharge, whichever comes first, up to 30 days

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: DR. FRANZ KOHLER CHEMIE GMBH

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2017
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): March 31, 2017

Study Record Updates

• Last Update Posted (Actual): March 11, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Delirium; Critical Illness
• Other Study ID Numbers: CADUCeuS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO