title: The attributable mortality of delirium in critically ill patients: prospective cohort study.
abstract: OBJECTIVE
  To determine the attributable mortality caused by delirium in critically ill patients.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  32 mixed bed intensive care unit in the Netherlands, January 2011 to July 2013.
  
  
  METHODS
  1112 consecutive adults admitted to an intensive care unit for a minimum of 24 hours.
  
  
  METHODS
  Trained observers evaluated delirium daily using a validated protocol. Logistic regression and competing risks survival analyses were used to adjust for baseline variables and a marginal structural model analysis to adjust for confounding by evolution of disease severity before the onset of delirium.
  
  
  METHODS
  Mortality during admission to an intensive care unit.
  
  
  RESULTS
  Among 1112 evaluated patients, 558 (50.2%) developed at least one episode of delirium, with a median duration of 3 days (interquartile range 2-7 days). Crude mortality was 94/558 (17%) in patients with delirium compared with 40/554 (7%) in patients without delirium (P<0.001). Delirium was significantly associated with mortality in the multivariable logistic regression analysis (odds ratio 1.77, 95% confidence interval 1.15 to 2.72) and survival analysis (subdistribution hazard ratio 2.08, 95% confidence interval 1.40 to 3.09). However, the association disappeared after adjustment for time varying confounders in the marginal structural model (subdistribution hazard ratio 1.19, 95% confidence interval 0.75 to 1.89). Using this approach, only 7.2% (95% confidence interval -7.5% to 19.5%) of deaths in the intensive care unit were attributable to delirium, with an absolute mortality excess in patients with delirium of 0.9% (95% confidence interval -0.9% to 2.3%) by day 30. In post hoc analyses, however, delirium that persisted for two days or more remained associated with a 2.0% (95% confidence interval 1.2% to 2.8%) absolute mortality increase. Furthermore, competing risk analysis showed that delirium of any duration was associated with a significantly reduced rate of discharge from the intensive care unit (cause specific hazard ratio 0.65, 95% confidence interval 0.55 to 0.76).
  
  
  CONCLUSIONS
  Overall, delirium prolongs admission in the intensive care unit but does not cause death in critically ill patients. Future studies should focus on episodes of persistent delirium and its long term sequelae rather than on acute mortality.Trial registration Clinicaltrials.gov NCT01905033.
authors.affiliation: Department of Intensive Care Medicine, University Medical Centre Utrecht, 3508 GA, Utrecht, Netherlands p.m.c.kleinklouwenberg@umcutrecht.nl.
authors.forename: Peter M C
authors.initials: PM
authors.lastname: Klein Klouwenberg
authors.affiliation: Department of Intensive Care Medicine, University Medical Centre Utrecht, 3508 GA, Utrecht, Netherlands.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Zaal
authors.affiliation: Department of Mathematics, Utrecht University, Utrecht, Netherlands.
authors.forename: Cristian
authors.initials: C
authors.lastname: Spitoni
authors.affiliation: Department of Intensive Care Medicine, University Medical Centre Utrecht, 3508 GA, Utrecht, Netherlands.
authors.forename: David S Y
authors.initials: DS
authors.lastname: Ong
authors.affiliation: Department of Intensive Care Medicine, University Medical Centre Utrecht, 3508 GA, Utrecht, Netherlands.
authors.forename: Arendina W
authors.initials: AW
authors.lastname: van der Kooi
authors.affiliation: Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.affiliation: Department of Intensive Care Medicine, University Medical Centre Utrecht, 3508 GA, Utrecht, Netherlands.
authors.forename: Arjen J C
authors.initials: AJ
authors.lastname: Slooter
authors.affiliation: Department of Intensive Care Medicine, University Medical Centre Utrecht, 3508 GA, Utrecht, Netherlands.
authors.forename: Olaf L
authors.initials: OL
authors.lastname: Cremer
mesh_terms: D000368:Aged; D003422:Critical Care; D016638:Critical Illness / Q000401:mortality*; D003693:Delirium / Q000401:mortality*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D007902:Length of Stay / Q000706:statistics & numerical data*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D011446:Prospective Studies; D016019:Survival Analysis