The Attributable Mortality of Delirium in Critically Ill Patients: Prospective Cohort Study

Overview

Journal BMJ

Specialty General Medicine

Date 2014 Nov 26

PMID 25422275

Citations 73

Authors

Peter M C Klein Klouwenberg

Irene J Zaal

Cristian Spitoni

David S Y Ong

Arendina W van der Kooi

Marc J M Bonten

Arjen J C Slooter

Olaf L Cremer

Affiliations

Soon will be listed here.

Abstract

Objective: To determine the attributable mortality caused by delirium in critically ill patients.

Design: Prospective cohort study.

Setting: 32 mixed bed intensive care unit in the Netherlands, January 2011 to July 2013.

Participants: 1112 consecutive adults admitted to an intensive care unit for a minimum of 24 hours.

Exposures: 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.

Main Outcome Measure: 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.

Citing Articles

Protocol for a meta-review of interventions to prevent and manage ICU delirium.

Jones K, Kundakci B, Booth A, Pufulete M, Gibbison B BMJ Open. 2025; 15(2):e090815.

PMID: 39933812 PMC: 11815468. DOI: 10.1136/bmjopen-2024-090815.

Overtime work of anesthesiologists is associated with increased delirium in older patients admitted to intensive care unit after noncardiac surgery: a secondary analysis.

Zhao Y, Chen N, Su X, Ma J, Wang D BMC Anesthesiol. 2024; 24(1):465.

PMID: 39701984 PMC: 11658087. DOI: 10.1186/s12871-024-02825-x.

Effect of occupational therapy on the occurrence of delirium in critically ill patients: a systematic review and meta-analysis.

Zhao J, Fan K, Zheng S, Xie G, Niu X, Pang J Front Neurol. 2024; 15:1391993.

PMID: 39105057 PMC: 11298357. DOI: 10.3389/fneur.2024.1391993.

Impact of Delirium Onset and Duration on Mortality in Patients With Cancer Admitted to the ICU.

Tao J, Seier K, Chawla S, Tan K, Wheeler A, Sanzone J J Intensive Care Med. 2024; 39(9):900-908.

PMID: 38629453 PMC: 11898015. DOI: 10.1177/08850666241244733.

A joint frailty model for recurrent and competing terminal events: Application to delirium in the ICU.

Etzkorn L, Coent Q, van den Boogaard M, Rondeau V, Colantuoni E Stat Med. 2024; 43(12):2389-2402.

PMID: 38564224 PMC: 11258962. DOI: 10.1002/sim.10053.

References

Woods J, Mion L, Connor J, Viray F, Jahan L, Huber C . Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes. Intensive Care Med. 2004; 30(6):1066-72. DOI: 10.1007/s00134-004-2193-9. View

Engels J, Diehr P . Imputation of missing longitudinal data: a comparison of methods. J Clin Epidemiol. 2003; 56(10):968-76. DOI: 10.1016/s0895-4356(03)00170-7. View

Aldemir M, Ozen S, Kara I, Sir A, Bac B . Predisposing factors for delirium in the surgical intensive care unit. Crit Care. 2001; 5(5):265-70. PMC: 83853. DOI: 10.1186/cc1044. View

van den Boogaard M, Pickkers P, Slooter A, Kuiper M, Spronk P, van der Voort P . Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study. BMJ. 2012; 344:e420. PMC: 3276486. DOI: 10.1136/bmj.e420. View

van den Boogaard M, Schoonhoven L, van der Hoeven J, van Achterberg T, Pickkers P . Incidence and short-term consequences of delirium in critically ill patients: A prospective observational cohort study. Int J Nurs Stud. 2011; 49(7):775-83. DOI: 10.1016/j.ijnurstu.2011.11.016. View

Zhang Z, Pan L, Ni H . Impact of delirium on clinical outcome in critically ill patients: a meta-analysis. Gen Hosp Psychiatry. 2012; 35(2):105-11. DOI: 10.1016/j.genhosppsych.2012.11.003. View

van Gool W, van de Beek D, Eikelenboom P . Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet. 2010; 375(9716):773-5. DOI: 10.1016/S0140-6736(09)61158-2. View

Ouimet S, Kavanagh B, Gottfried S, Skrobik Y . Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2006; 33(1):66-73. DOI: 10.1007/s00134-006-0399-8. View

Zaal I, Spruyt C, Peelen L, van Eijk M, Wientjes R, Schneider M . Intensive care unit environment may affect the course of delirium. Intensive Care Med. 2012; 39(3):481-8. DOI: 10.1007/s00134-012-2726-6. View

10.

Pisani M, Murphy T, Araujo K, Slattum P, Van Ness P, Inouye S . Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med. 2008; 37(1):177-83. PMC: 2700732. DOI: 10.1097/CCM.0b013e318192fcf9. View

11.

Martin B, Buth K, Arora R, Baskett R . Delirium as a predictor of sepsis in post-coronary artery bypass grafting patients: a retrospective cohort study. Crit Care. 2010; 14(5):R171. PMC: 3219273. DOI: 10.1186/cc9273. View

12.

Schweickert W, Pohlman M, Pohlman A, Nigos C, Pawlik A, Esbrook C . Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009; 373(9678):1874-82. PMC: 9906655. DOI: 10.1016/S0140-6736(09)60658-9. View

13.

Pisani M, Murphy T, Araujo K, Van Ness P . Factors associated with persistent delirium after intensive care unit admission in an older medical patient population. J Crit Care. 2010; 25(3):540.e1-7. PMC: 2939229. DOI: 10.1016/j.jcrc.2010.02.009. View

14.

MacLullich A, Ferguson K, Miller T, de Rooij S, Cunningham C . Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses. J Psychosom Res. 2008; 65(3):229-38. PMC: 4311661. DOI: 10.1016/j.jpsychores.2008.05.019. View

15.

Zaal I, Slooter A . Delirium in critically ill patients: epidemiology, pathophysiology, diagnosis and management. Drugs. 2012; 72(11):1457-71. DOI: 10.2165/11635520-000000000-00000. View

16.

McNicoll L, Pisani M, Zhang Y, Wesley Ely E, Siegel M, Inouye S . Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc. 2003; 51(5):591-8. DOI: 10.1034/j.1600-0579.2003.00201.x. View

17.

Jaber S, Chanques G, Altairac C, Sebbane M, Vergne C, Perrigault P . A prospective study of agitation in a medical-surgical ICU: incidence, risk factors, and outcomes. Chest. 2005; 128(4):2749-57. DOI: 10.1378/chest.128.4.2749. View

18.

Kurth T, Walker A, Glynn R, Chan K, Gaziano J, Berger K . Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect. Am J Epidemiol. 2005; 163(3):262-70. DOI: 10.1093/aje/kwj047. View

19.

Pandharipande P, Cotton B, Shintani A, Thompson J, Pun B, Morris Jr J . Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma. 2008; 65(1):34-41. PMC: 3773485. DOI: 10.1097/TA.0b013e31814b2c4d. View

20.

Pandharipande P, Shintani A, Peterson J, Pun B, Wilkinson G, Dittus R . Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006; 104(1):21-6. DOI: 10.1097/00000542-200601000-00005. View