Outcome of delirium in critically ill patients: systematic review and meta-analysis

Jorge I F Salluh, Han Wang, Eric B Schneider, Neeraja Nagaraja, Gayane Yenokyan, Abdulla Damluji, Rodrigo B Serafim, Robert D Stevens, Jorge I F Salluh, Han Wang, Eric B Schneider, Neeraja Nagaraja, Gayane Yenokyan, Abdulla Damluji, Rodrigo B Serafim, Robert D Stevens

Abstract

Objectives: To determine the relation between delirium in critically ill patients and their outcomes in the short term (in the intensive care unit and in hospital) and after discharge from hospital.

Design: Systematic review and meta-analysis of published studies.

Data sources: PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 January 2015.

Eligibility criteria for selection studies: Reports were eligible for inclusion if they were prospective observational cohorts or clinical trials of adults in intensive care units who were assessed with a validated delirium screening or rating system, and if the association was measured between delirium and at least one of four clinical endpoints (death during admission, length of stay, duration of mechanical ventilation, and any outcome after hospital discharge). Studies were excluded if they primarily enrolled patients with a neurological disorder or patients admitted to intensive care after cardiac surgery or organ/tissue transplantation, or centered on sedation management or alcohol or substance withdrawal. Data were extracted on characteristics of studies, populations sampled, identification of delirium, and outcomes. Random effects models and meta-regression analyses were used to pool data from individual studies.

Results: Delirium was identified in 5280 of 16,595 (31.8%) critically ill patients reported in 42 studies. When compared with control patients without delirium, patients with delirium had significantly higher mortality during admission (risk ratio 2.19, 94% confidence interval 1.78 to 2.70; P<0.001) as well as longer durations of mechanical ventilation and lengths of stay in the intensive care unit and in hospital (standard mean differences 1.79 (95% confidence interval 0.31 to 3.27; P<0.001), 1.38 (0.99 to 1.77; P<0.001), and 0.97 (0.61 to 1.33; P<0.001), respectively). Available studies indicated an association between delirium and cognitive impairment after discharge.

Conclusions: Nearly a third of patients admitted to an intensive care unit develop delirium, and these patients are at increased risk of dying during admission, longer stays in hospital, and cognitive impairment after discharge.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

© Salluh et al 2015.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794005/bin/salj023399.f1_default.jpg
Fig 1 Selection of studies on outcome of delirium in critically ill patients
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794005/bin/salj023399.f2_default.jpg
Fig 2 Funnel plot of mortality in critically ill patients with delirium
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794005/bin/salj023399.f3_default.jpg
Fig 3 Impact of delirium on hospital mortality in critically ill patients
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794005/bin/salj023399.f4_default.jpg
Fig 4 Impact of delirium on length of stay (days) in intensive care unit in critically ill patients
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794005/bin/salj023399.f5_default.jpg
Fig 5 Impact of delirium on length of stay (days) in hospital in critically ill patients
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4794005/bin/salj023399.f6_default.jpg
Fig 6 Impact of delirium on duration (days) of mechanical ventilation in critically ill patients

References

    1. Inouye SK, Viscoli CM, Horwitz RI, et al. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993;119:474-81.
    1. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. American Psychiatric Association, 2000.
    1. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-62.
    1. Lin S, Liu C, Wang C, et al. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med 2004;32:2254-59.
    1. Pompei P, Foreman M, Rudberg MA, et al. Delirium in hospitalized older persons: outcomes and predictors. J Am Geriatr Soc 1994;42:809-15.
    1. Buss MK, Vanderwerker LC, Inouye SK, et al. Associations between caregiver-perceived delirium in patients with cancer and generalized anxiety in their caregivers. J Palliat Med 2007;10:1083-92.
    1. Shankar KN, Hirschman KB, Hanlon AL, et al. Burden in caregivers of cognitively impaired elderly adults at time of hospitalization: a cross-sectional analysis. J Am Geriatr Soc 2014;62:276-84.
    1. Milbrandt EB, Deppen S, Harrison PL, et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004;32:955-62.
    1. Leslie DL, Marcantonio ER, Zhang Y, et al. One-year health care costs associated with delirium in the elderly population. Arch Intern Med 2008;168:27-32.
    1. Pisani MA, Kong SY, Kasl SV, et al. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009;180:1092-7.
    1. O’Keeffe S, Lavan J. The prognostic significance of delirium in older hospital patients. J Am Geriatr Soc 1997;45:174-8.
    1. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med 2013;369:1306-16.
    1. Witlox J, Eurelings LS, de Jonghe JF, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 2010;304:443-51.
    1. Levkoff SE, Evans DA, Liptzin B, et al. Delirium. The occurrence and persistence of symptoms among elderly hospitalized patients. Arch Intern Med 1992;152:334-40.
    1. Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Arch Intern Med 2000;160:786-94.
    1. Balas MC, Happ MB, Yang W, et al. Outcomes associated with delirium in older patients in surgical ICUs. Chest 2009;135:18-25.
    1. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:2703-10.
    1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911-22.
    1. Aldemir M, Ozen S, Kara IH, et al. Predisposing factors for delirium in the surgical intensive care unit. Crit Care 2001;5:265-70.
    1. Van Eijk MM, van Marum RJ, Klijn IA, et al. Comparison of delirium assessment tools in a mixed intensive care unit. Crit Care Med 2009;37:1881-5.
    1. Spronk PE, Riekerk B, Hofhuis J, et al. Occurrence of delirium is severely underestimated in the ICU during daily care. Intensive Care Med 2009;35:1276-80.
    1. Thomason JW, Shintani A, Peterson JF, et al. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care 2005;9:R375-81.
    1. Ranhoff AH, Rozzini R, Sabatini T, et al. Delirium in a sub-intensive care unit for the elderly: occurrence and risk factors. Aging Clin Exp Res 2006;18:440-5.
    1. Page VJ, Navarange S, Gama S, et al. Routine delirium monitoring in a UK critical care unit. Crit Care 2009;13:R16.
    1. Dubois MJ, Bergeron N, Dumont M, et al. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001;27:1297-304.
    1. Micek ST, Anand NJ, Laible BR, et al. Delirium as detected by the CAM-ICU predicts restraint use among mechanically ventilated medical patients. Crit Care Med 2005;33:1260-5.
    1. Roberts B, Rickard CM, Rajbhandari D, et al. Multicentre study of delirium in ICU patients using a simple screening tool. Aust Crit Care 2005;18:6-14.
    1. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 2000;283:2008-12.
    1. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990;113:941-8.
    1. Bergeron N, Dubois MJ, Dumont M, et al. Intensive care delirium screening checklist: evaluation of a new screening tool. Intensive Care Med 2001;27:859-64.
    1. Neelon VJ, Champagne MT, Carlson JR, et al. The NEECHAM confusion scale: construction, validation, and clinical testing. Nurs Res 1996;45:324-30.
    1. Wells GA SB, O’Connell D, Peterson J, Welch V, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute, 2000. .
    1. Stevens RD, Dowdy DW, Michaels RK, et al. Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med 2007;33:1876-91.
    1. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
    1. Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res 1993;2:121-45.
    1. Friedrich JO, Adhikari NK, Beyene J. Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol 2007;7:5.
    1. Sweeting MJ, Sutton AJ, Lambert PC. What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 2004;23:1351-75.
    1. Sankey SS, Weissfeld LA, Fine MJ, et al. An assessment of the use of the continuity correction for sparse data in meta-analysis. Commun Stat Simul Comput 1996;25:1031-56.
    1. Thiessen Philbrook H, Barrowman N, Garg AX. Imputing variance estimates do not alter the conclusions of a meta-analysis with continuous outcomes: a case study of changes in renal function after living kidney donation. J Clin Epidemiol 2007;60:228-40.
    1. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
    1. Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med 2006;25:3443-57.
    1. Marquis F, Ouimet S, Riker R, et al. Individual delirium symptoms: do they matter? Crit Care Med 2007;35:2533-7.
    1. Ouimet S, Kavanagh BP, Gottfried SB, et al. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007;33:66-73.
    1. Brummel NE, Jackson JC, Pandharipande PP, et al. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Crit Care Med 2014;42:369-77.
    1. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010;87:1513-20.
    1. Shehabi Y, Riker RR, Bokesch PM, et al. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med 2010;38:2311-8.
    1. Van den Boogaard M, Schoonhoven L, Evers AW, et al. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med 2012;40:112-8.
    1. Wolters AE, van Dijk D, Pasma W, et al. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit Care 2014;18:R125.
    1. Angles EM, Robinson TN, Biffl WL, et al. Risk factors for delirium after major trauma. Am J Surg 2008;196:864-70.
    1. Heymann A, Radtke F, Schiemann A, et al. Delayed treatment of delirium increases mortality rate in intensive care unit patients. J Int Med Res 2010;38:1584-95.
    1. Kishi Y, Iwasaki Y, Takezawa K, et al. Delirium in critical care unit patients admitted through an emergency room. Gen Hosp Psychiatry 1995;17:371-9.
    1. Lat I, McMillian W, Taylor S, et al. The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med 2009;37:1898-905.
    1. Lin SM, Huang CD, Liu CY, et al. Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients. J Crit Care 2008;23:372-9.
    1. Plaschke K, von Haken R, Scholz M, et al. Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s). Intensive Care Med 2008;34:431-6.
    1. Salluh JI, Soares M, Teles JM, et al. Delirium epidemiology in critical care (DECCA): an international study. Crit Care 2010;14:R210.
    1. Tsuruta R, Nakahara T, Miyauchi T, et al. Prevalence and associated factors for delirium in critically ill patients at a Japanese intensive care unit. Gen Hosp Psychiatry 2010;32:607-11.
    1. Van den Boogaard M, Peters SA, van der Hoeven JG, et al. The impact of delirium on the prediction of in-hospital mortality in intensive care patients. Crit Care 2010;14:R146.
    1. Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, et al. Long term outcome after delirium in the intensive care unit. J Clin Nurs 2009;18:3349-57.
    1. Almeida IC, Soares M, Bozza FA, et al. The impact of acute brain dysfunction in the outcomes of mechanically ventilated cancer patients. PloS One 2014;9:e85332.
    1. Serafim RB, Dutra MF, Saddy F, et al. Delirium in postoperative nonventilated intensive care patients: risk factors and outcomes. Ann Intensive Care 2012;2:51.
    1. Sharma A, Malhotra S, Grover S, et al. Incidence, prevalence, risk factor and outcome of delirium in intensive care unit: a study from India. Gen Hosp Psychiatry 2012;34:639-46.
    1. Tomasi CD, Grandi C, Salluh J, et al. Comparison of CAM-ICU and ICDSC for the detection of delirium in critically ill patients focusing on relevant clinical outcomes. J Crit Care 2012;27:212-7.
    1. Tsuruta R, Oda Y, Shintani A, et al. Delirium and coma evaluated in mechanically ventilated patients in the intensive care unit in Japan: a multi-institutional prospective observational study. J Crit Care 2014;29:472.e1-5.
    1. Van den Boogaard M, Kox M, Quinn KL, et al. Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and noninflamed patients. Crit Care 2011;15:R297.
    1. Van den Boogaard M, Schoonhoven L, Maseda E, et al. Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study. Intensive Care Med 2014;40:361-9.
    1. Lahariya S, Grover S, Bagga S, et al. Delirium in patients admitted to a cardiac intensive care unit with cardiac emergencies in a developing country: incidence, prevalence, risk factor and outcome. Gen Hosp Psychiatry 2014;36:156-64.
    1. Mehta S, Cook D, Devlin JW, et al. Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Crit Care Med 2015;43:557-66.
    1. Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, et al. A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in non-intubated patients. Crit Care 2008;12:R16.
    1. Yamaguchi T, Tsukioka E, Kishi Y. Outcomes after delirium in a Japanese intensive care unit. Gen Hosp Psychiatry 2014;36:634-6.
    1. Klein Klouwenberg PM, Zaal IJ, Spitoni C, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ 2014;349:g6652.
    1. Kamdar BB, King LM, Collop NA, et al. The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit Care Med 2013;41:800-9.
    1. Zhang Z, Pan L, Ni H. Impact of delirium on clinical outcome in critically ill patients: a meta-analysis. Gen Hosp Psychiatry 2013;35:105-11.
    1. Barr J, Fraser GL, Puntillo K, 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;41:263-306.
    1. Sieber FE, Zakriya KJ, Gottschalk A, et al. Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc 2010;85:18-26.
    1. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009;301:489-99.
    1. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007;298:2644-53.
    1. Fraser GL, Devlin JW, Worby CP, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med 2013;41(suppl 1):S30-8.
    1. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009;373:1874-82.
    1. Wang W, Li HL, Wang DX, et al. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. Crit Care Med 2012;40:731-9.
    1. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010;38:419-27.
    1. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc 2005;53:1658-66.
    1. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 1999;340:669-76.
    1. Reston JT, Schoelles KM. In-facility delirium prevention programs as a patient safety strategy: a systematic review. Ann Intern Med 2013;158:375-80.
    1. Patel SB, Poston JT, Pohlman A, et al. Rapidly reversible, sedation-related delirium versus persistent delirium in the intensive care unit. Am J Respir Crit Care Med 2014;189:658-65.
    1. Widmann CN, Heneka MT. Long-term cerebral consequences of sepsis. Lancet Neurol 2014;13:630-6.
    1. Hsieh SJ, Soto GJ, Hope AA, et al. The association between acute respiratory distress syndrome, delirium, and in-hospital mortality in intensive care unit patients. Am J Respir Crit Care Med 2015;191:71-8.
    1. Stevens RD, Sharshar T, Ely EW. Brain disorders in critical illness: mechanisms, diagnosis, and treatment. Cambridge University Press, 2013.

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