title: Anticholinergic Medication Use and Transition to Delirium in Critically Ill Patients: A Prospective Cohort Study.
abstract: OBJECTIVE
  Although cholinergic deficiency is presumed to increase delirium risk and use of medication with anticholinergic properties in the ICU is frequent, the relationship between anticholinergic medication use and delirium in this setting remains unclear. We investigated whether exposure to medication with anticholinergic properties increases the probability of transitioning to delirium in critically ill adults and whether this relationship is affected by age or the presence of acute systemic inflammation.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  A 32-bed medical-surgical ICU at an academic medical center.
  
  
  METHODS
  Critically ill adults admitted to the ICU for more than 24 hours without an acute neurological disorder or another condition that would hamper delirium assessment.
  
  
  METHODS
  None.
  
  
  RESULTS
  Daily anticholinergic burden was calculated for each patient based on the sum of the Anticholinergic Drug Scale score for each medication administered. Daily mental status was classified as "coma," "delirium," or an "awake without delirium" state. The primary outcome, the daily transition from an "awake without delirium" state to "delirium," was analyzed using a first-order Markov model that adjusted for eight covariables. A total of 1,112 patients were evaluated over 9,867 ICU days. The daily median summed Anticholinergic Drug Scale score was 2 (interquartile range, 1-3). The transition from being in an "awake without delirium" state to "delirium" occurred on 562 of ICU days (6%). After correcting for confounding, a one-unit increase in the Anticholinergic Drug Scale score resulted in a nonsignificant increase in the probability of delirium occurring the next day (odds ratio, 1.05; 95% CI, 0.99-1.10). Neither age nor the presence of acute systemic inflammation modified this relationship.
  
  
  CONCLUSIONS
  Exposure to medication with anticholinergic properties, as defined by the Anticholinergic Drug Scale, does not increase the probability of delirium onset in patients who are awake and not delirious in the ICU.
authors.affiliation: 1Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. 2Institute of Psychology, Health, Medical, and Neuropsychology Unit, Faculty of Social Sciences, Leiden University, Leiden, The Netherlands. 3School of Pharmacy, Northeastern University, Boston, MA.
authors.forename: Annemiek E
authors.initials: AE
authors.lastname: Wolters
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Zaal
authors.forename: Dieuwke S
authors.initials: DS
authors.lastname: Veldhuijzen
authors.forename: Olaf L
authors.initials: OL
authors.lastname: Cremer
authors.forename: John W
authors.initials: JW
authors.lastname: Devlin
authors.forename: Diederik
authors.initials: D
authors.lastname: van Dijk
authors.forename: Arjen J C
authors.initials: AJ
authors.lastname: Slooter
mesh_terms: D000046:Academic Medical Centers; D000367:Age Factors; D000368:Aged; D018680:Cholinergic Antagonists / Q000009:adverse effects*; D015897:Comorbidity; D016638:Critical Illness; D003693:Delirium / Q000139:chemically induced*; D005260:Female; D006304:Health Status; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D018680:Cholinergic Antagonists