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Critical care (London, England)
12 06, 2022;26 (1): 377.

Association between cholinesterase activity and critical illness brain dysfunction.

Christopher G Hughes, Christina S Boncyk, Benjamin Fedeles, Pratik P Pandharipande, Wencong Chen, Mayur B Patel, Nathan E Brummel, James C Jackson, Rameela Raman, E Wesley Ely, Timothy D Girard
Author Information
  1. Christopher G Hughes: Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, 1211 21st Ave. South, 422 MAB, Nashville, TN, 37212, USA. christopher.hughes@vumc.org.
  2. Christina S Boncyk: Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, 1211 21st Ave. South, 422 MAB, Nashville, TN, 37212, USA.
  3. Benjamin Fedeles: United States Air Force, Washington, USA.
  4. Pratik P Pandharipande: Departments of Anesthesiology and Surgery, Division of Anesthesiology Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  5. Wencong Chen: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA.
  6. Mayur B Patel: Department of Surgery, Division of Acute Care Surgery and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  7. Nathan E Brummel: Division of Allergy, Critical Care and Sleep Medicine, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  8. James C Jackson: Department of Medicine, Division of Pulmonary and Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  9. Rameela Raman: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA.
  10. E Wesley Ely: Department of Medicine, Division of Pulmonary and Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  11. Timothy D Girard: Department of Critical Care Medicine and Clinical Research, Investigation, and Systems Modeling of Acute Illnesses Center, University of Pittsburgh, Pittsburgh, PA, USA.
PMID: 36474266 DOI: 10.1186/s13054-022-04260-1

Abstract

BACKGROUND: Delirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity. We hypothesized that cholinesterase activity during critical illness would be associated with delirium in the intensive care unit (ICU) and cognitive impairment after discharge.
METHODS: We enrolled adults with respiratory failure and/or shock and measured plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity on days 1, 3, 5, and 7 after enrollment. AChE values were also normalized per gram of hemoglobin (AChE/Hgb). We assessed for coma and delirium twice daily using the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU to evaluate daily mental status (delirium, coma, normal) and days alive without delirium or coma. Cognitive impairment, disability, and health-related quality of life were assessed at up to 6 months post-discharge. We used multivariable regression to determine whether AChE, AChE/Hgb, and BChE activity were associated with outcomes after adjusting for relevant covariates.
RESULTS: We included 272 critically ill patients who were a median (IQR) age 56 (39-67) years and had a median Sequential Organ Failure Assessment score at enrollment of 8 (5-11). Higher daily AChE levels were associated with increased odds of being delirious versus normal mental status on the same day (Odds Ratio [95% Confidence Interval] 1.64 [1.11, 2.43]; P = 0.045). AChE/Hgb and BChE activity levels were not associated with delirious mental status. Lower enrollment BChE was associated with fewer days alive without delirium or coma (P = 0.048). AChE, AChE/Hgb, and BChE levels were not significantly associated with cognitive impairment, disability, or quality of life after discharge.
CONCLUSION: Cholinesterase activity during critical illness is associated with delirium but not with outcomes after discharge, findings that may reflect mechanisms of acute brain organ dysfunction.
TRIAL REGISTRATION: NCT03098472. Registered 31 March 2017.

Keywords

Acetylcholinesterase Butyrylcholinesterase Cognitive impairment Critical illness Delirium

Associated Data

ClinicalTrials.gov | NCT03098472

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MeSH Term

Humans
Middle Aged
Critical Illness
Butyrylcholinesterase
Acetylcholinesterase
Quality of Life
Aftercare
Patient Discharge
Brain

Chemicals

Butyrylcholinesterase
Acetylcholinesterase
Journal Article
Article has an altmetric score of 18

Word Cloud

Created with Highcharts 10.0.0associatedactivitydeliriumimpairmentillnessAChEBChEbraindysfunctioncriticalcomacognitivecholinesterasedischargedaysenrollmentAChE/HgbdailymentalstatuslevelsDeliriumacutehypothesizedcholinergicICU1assessedAssessmentnormalalivewithoutCognitivedisabilityqualitylifeoutcomesmediandeliriousP = 0BACKGROUND:frequentmanifestationmechanismcenteredneuroinflammationregulatedpartsystemPoint-of-careserumenzymemeasurementsservereal-timeindexintensivecareunitMETHODS:enrolledadultsrespiratoryfailureand/orshockmeasuredplasmaacetylcholinesterasebutyrylcholinesterase357valuesalsonormalizedpergramhemoglobintwiceusingRichmondAgitationSedationScaleConfusionMethodevaluatehealth-related6 monthspost-dischargeusedmultivariableregressiondeterminewhetheradjustingrelevantcovariatesRESULTS:included272criticallyillpatientsIQRage5639-67yearsSequentialOrganFailurescore85-11HigherincreasedoddsversusdayOddsRatio[95%ConfidenceInterval]64[111243]045Lowerfewer048 AChE/Hgb andsignificantlyCONCLUSION:CholinesterasefindingsmayreflectmechanismsorganTRIALREGISTRATION:NCT03098472Registered31March2017AssociationAcetylcholinesteraseButyrylcholinesteraseCritical

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