Association between incident delirium and 28- and 90-day mortality in critically ill adults: a secondary analysis

Matthew S Duprey, Mark van den Boogaard, Johannes G van der Hoeven, Peter Pickkers, Becky A Briesacher, Jane S Saczynski, John L Griffith, John W Devlin, Matthew S Duprey, Mark van den Boogaard, Johannes G van der Hoeven, Peter Pickkers, Becky A Briesacher, Jane S Saczynski, John L Griffith, John W Devlin

Abstract

Background: While delirium prevalence and duration are each associated with increased 30-day, 6-month, and 1-year mortality, the association between incident ICU delirium and mortality remains unclear. We evaluated the association between both incident ICU delirium and days spent with delirium in the 28 days after ICU admission and mortality within 28 and 90 days.

Methods: Secondary cohort analysis of a randomized, double-blind, placebo-controlled trial conducted among 1495 delirium-free, critically ill adults in 14 Dutch ICUs with an expected ICU stay ≥2 days where all delirium assessments were completed. In the 28 days after ICU admission, patients were evaluated for delirium and coma 3x daily; each day was coded as a delirium day [≥1 positive Confusion Assessment Method for the ICU (CAM-ICU)], a coma day [no delirium and ≥ 1 Richmond Agitation Sedation Scale (RASS) score ≤ - 4], or neither. Four Cox-regression models were constructed for 28-day mortality and 90-day mortality; each accounted for potential confounders (i.e., age, APACHE-II score, sepsis, use of mechanical ventilation, ICU length of stay, and haloperidol dose) and: 1) delirium occurrence, 2) days spent with delirium, 3) days spent in coma, and 4) days spent with delirium and/or coma.

Results: Among the 1495 patients, 28 day mortality was 17% and 90 day mortality was 21%. Neither incident delirium (28 day mortality hazard ratio [HR] = 1.02, 95%CI = 0.75-1.39; 90 day mortality HR = 1.05, 95%CI = 0.79-1.38) nor days spent with delirium (28 day mortality HR = 1.00, 95%CI = 0.95-1.05; 90 day mortality HR = 1.02, 95%CI = 0.98-1.07) were significantly associated with mortality. However, both days spent with coma (28 day mortality HR = 1.05, 95%CI = 1.02-1.08; 90 day mortality HR = 1.05, 95%CI = 1.02-1.08) and days spent with delirium or coma (28 day mortality HR = 1.03, 95%CI = 1.00-1.05; 90 day mortality HR = 1.03, 95%CI = 1.01-1.06) were significantly associated with mortality.

Conclusions: This analysis suggests neither incident delirium nor days spent with delirium are associated with short-term mortality after ICU admission.

Trial registration: ClinicalTrials.gov, Identifier NCT01785290 Registered 7 February 2013.

Keywords: Coma; Delirium; Intensive care; Mortality; Risk factors.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart for inclusion within the analytic cohort
Fig. 2
Fig. 2
Graphical representation of the neurologicstatus for the remaining patients alive and in the ICU on each ICU day for the 28 days after ICU admission. Each patient was coded to one of three states [delirium, coma, or neither delirium nor coma (normal)]
Fig. 3
Fig. 3
Survival curve over 28 and 90 days after ICU admission stratified by presence of incident delirium
Fig. 4
Fig. 4
Survival curve over 28 and 90 days after ICU admission stratified by presence of coma

References

    1. Zaal IJ, Slooter AJ. Delirium in critically ill patients: epidemiology, pathophysiology, diagnosis and management. Drugs. 2012;72(11):1457–1471.
    1. Wolters AE, Slooter AJ, van der Kooi AW, van Dijk D. Cognitive impairment after intensive care unit admission: a systematic review. Intensive Care Med. 2013;39(3):376–386.
    1. Lokhandwala S, McCague N, Chahin A, Escobar B, Feng M, Ghassemi MM, et al. One-year mortality after recovery from critical illness: a retrospective cohort study. PLoS One. 2018;13(5):e0197226.
    1. Angus DC, Barnato AE, Linde-Zwirble WT, Weissfeld LA, Watson RS, Rickert T, et al. Use of intensive care at the end of life in the United States: an epidemiologic study. Crit Care Med. 2004;32(3):638–643.
    1. Shehabi Y, Riker RR, Bokesch PM, Wisemandle W, Shintani A, Ely EW, et al. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med. 2010;38(12):2311–2318.
    1. Klein Klouwenberg PM, Zaal IJ, Spitoni C, Ong DS, van der Kooi AW, Bonten MJ, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652.
    1. Mehta S, Cook D, Devlin JW, Skrobik Y, Meade M, Fergusson D, et al. Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Crit Care Med. 2015;43(3):557–566.
    1. Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263–306.
    1. Zaal IJ, Devlin JW, Hazelbag M, Klein Klouwenberg PM, van der Kooi AW, Ong DS, et al. Benzodiazepine-associated delirium in critically ill adults. Intensive Care Med. 2015;41(12):2130–2137.
    1. Shehabi Y, Bellomo R, Kadiman S, Ti LK, Howe B, Reade MC, et al. Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: a multinational prospective longitudinal cohort study. Crit Care Med. 2018;46(6):850–859.
    1. Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186(8):724–731.
    1. Shehabi Y, Chan L, Kadiman S, Alias A, Ismail WN, Tan MA, et al. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med. 2013;39(5):910–918.
    1. van den Boogaard M, Schoonhoven L, van der Hoeven JG, 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. 2012;49(7):775–783.
    1. Salluh JI, Soares M, Teles JM, Ceraso D, Raimondi N, Nava VS, et al. Delirium epidemiology in critical care (decca): An international study. Crit Care. 2010;14(6):R210.
    1. Lat I, McMillian W, Taylor S, Janzen JM, Papadopoulos S, Korth L, et al. The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med. 2009;37(6):1898–1905.
    1. Lin SM, Liu CY, Wang CH, Lin HC, Huang CD, Huang PY, et al. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med. 2004;32(11):2254–2259.
    1. Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001;27(8):1297–1304.
    1. Kishi Y, Iwasaki Y, Takezawa K, Kurosawa H, Endo S. Delirium in critical care unit patients admitted through an emergency room. Gen Hosp Psychiatry. 1995;17(5):371–379.
    1. Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009;180(11):1092–1097.
    1. Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW. Intensive care unit delirium is an independent predictor of longer hospital stay: A prospective analysis of 261 non-ventilated patients. Critical Care (London, England) 2005;9(4):375.
    1. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. Jama. 2004;291(14):1753–1762.
    1. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007;33(1):66–73.
    1. van den Boogaard M, Slooter AJ, Bruggemann RJ, Schoonhoven L, Kuiper MA, van der Voort PH, et al. Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial. Trials. 2013;14:400.
    1. van den Boogaard M, Slooter AJC, Bruggemann RJM, Schoonhoven L, Beishuizen A, Vermeijden JW, et al. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the reduce randomized clinical trial. JAMA. 2018;319(7):680–690.
    1. Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, et al. The Richmond agitation-sedation scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338–1344.
    1. Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, et al. Evaluation of delirium in critically ill patients: validation of the confusion assessment method for the intensive care unit (CAM-ICU) Crit Care Med. 2001;29(7):1370–1379.
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–829.
    1. Colpan A, Akinci E, Erbay A, Balaban N, Bodur H. Evaluation of risk factors for mortality in intensive care units: a prospective study from a referral hospital in Turkey. Am J Infect Control. 2005;33(1):42–47.
    1. Song JE, Kim MH, Jeong WY, Jung IY, Oh DH, Kim YC, et al. Mortality risk factors for patients with septic shock after implementation of the surviving sepsis campaign bundles. Infect Chemother. 2016;48(3):199–208.
    1. Akaike H. A new look at the statistical identification model. IEEE Trans Autom Control. 1974;19:716.
    1. Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825–e873.
    1. Pun BT, Balas MC, Barnes-Daly MA, Thompson JL, Aldrich JM, Barr J, et al. Caring for critically ill patients with the ABCDEF bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med. 2019;47(1):3–14.
    1. Grover S, Ghosh A, Ghormode D. Experience in delirium: is it distressing? J Neuropsychiatry Clin Neurosci. 2015;27(2):139–146.
    1. Muhlhofer WG, Layfield S, Lowenstein D, Lin CP, Johnson RD, Saini S, et al. Duration of therapeutic coma and outcome of refractory status epilepticus. Epilepsia. 2019;60(5):921–934.
    1. Sonneville R, Verdonk F, Rauturier C, Klein IF, Wolff M, Annane D, et al. Understanding brain dysfunction in sepsis. Ann Intensive Care. 2013;3(1):15.
    1. Nelson BJ, Weinert CR, Bury CL, Marinelli WA, Gross CR. Intensive care unit drug use and subsequent quality of life in acute lung injury patients. Crit Care Med. 2000;28(11):3626–3630.
    1. Patel SB, Poston JT, Pohlman A, Hall JB, Kress JP. Rapidly reversible, sedation-related delirium versus persistent delirium in the intensive care unit. Am J Respir Crit Care Med. 2014;189(6):658–665.
    1. Rood PJT, van de Schoor F, van Tertholen K, Pickkers P, van den Boogaard M. Differences in 90-day mortality of delirium subtypes in the intensive care unit: a retrospective cohort study. J Crit Care. 2019;53:120–124.

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