In the Clinic
6 October 2020


Publication: Annals of Internal Medicine
Volume 173, Number 7


Delirium is an acute confusional state that is common and costly and is associated with significant functional decline and distress. It is the manifestation of acute encephalopathy and is variably called acute brain failure, acute brain dysfunction, or altered mental status. All patients are at risk for delirium, although those with more vulnerabilities (such as advanced age, exposures to other stressors like infection, and certain medications) are at higher risk. The pathophysiologic cause of delirium is not well understood. It is important to recognize patients at risk for and those with delirium and to immediately identify and treat factors contributing to it. There is no single intervention or medication to treat delirium, making it challenging to manage. Therefore, risk mitigation and prompt treatment rely on a sophisticated strategy to address the contributing factors. Delirium may be prevented or attenuated when multimodal strategies are used, thereby improving patient outcomes.

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Marcantonio ER. Delirium in hospitalized older adults. N Engl J Med. 2017;377:1456-66. [PMID: 29020579]  doi: 10.1056/NEJMcp1605501
Maldonado JR. Acute brain failure: pathophysiology, diagnosis, management, and sequelae of delirium. Crit Care Clin. 2017;33:461-519. [PMID: 28601132]  doi: 10.1016/j.ccc.2017.03.013
AGS/NIA Delirium Conference Writing Group, Planning Committee and Faculty.. The American Geriatrics Society/National Institute on Aging Bedside-to-Bench Conference: research agenda on delirium in older adults. J Am Geriatr Soc. 2015;63:843-52. [PMID: 25834932]  doi: 10.1111/jgs.13406
Slooter AJCOtte WMDevlin JWet al. Updated nomenclature of delirium and acute encephalopathy: statement of ten societies. Intensive Care Med. 2020;46:1020-2. [PMID: 32055887]  doi: 10.1007/s00134-019-05907-4
Robinson TNRaeburn CDTran ZVet al. Motor subtypes of postoperative delirium in older adults. Arch Surg. 2011;146:295-300. [PMID: 21422360]  doi: 10.1001/archsurg.2011.14
Chin YCKoh GCTay YKet al. Underdiagnosis of delirium on admission and prediction of patients who will develop delirium during their inpatient stay: a pilot study. Singapore Med J. 2016;57:18-21. [PMID: 26831312]  doi: 10.11622/smedj.2016007
Gleason LJSchmitt EMKosar CMet al. Effect of delirium and other major complications on outcomes after elective surgery in older adults. JAMA Surg. 2015;150:1134-40. [PMID: 26352694]  doi: 10.1001/jamasurg.2015.2606
Wang CGQin YFWan Xet al. Incidence and risk factors of postoperative delirium in the elderly patients with hip fracture. J Orthop Surg Res. 2018;13:186. [PMID: 30049276]  doi: 10.1186/s13018-018-0897-8
Chen WKe XWang Xet al. Prevalence and risk factors for postoperative delirium in total joint arthroplasty patients: a prospective study. Gen Hosp Psychiatry. 2017;46:55-61. [PMID: 28622817]  doi: 10.1016/j.genhosppsych.2017.03.008
Albrecht JSMarcantonio ERRoffey DMet alFunctional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair Cognitive Ancillary Study Investigators.. Stability of postoperative delirium psychomotor subtypes in individuals with hip fracture. J Am Geriatr Soc. 2015;63:970-6. [PMID: 25943948]  doi: 10.1111/jgs.13334
Watt CLMomoli FAnsari MTet al. The incidence and prevalence of delirium across palliative care settings: a systematic review. Palliat Med. 2019;33:865-77. [PMID: 31184538]  doi: 10.1177/0269216319854944
Ely EWInouye SKBernard GRet 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. [PMID: 11730446]
Pandharipande PPGirard TDJackson JCet alBRAIN-ICU Study Investigators.. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306-16. [PMID: 24088092]  doi: 10.1056/NEJMoa1301372
Kosar CMThomas KSInouye SKet al. Delirium during postacute nursing home admission and risk for adverse outcomes. J Am Geriatr Soc. 2017;65:1470-5. [PMID: 28338215]  doi: 10.1111/jgs.14823
National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. Clinical guideline CG103. Updated 14 March 2019. Accessed at on 14 August 2020.
Kotfis KWilliams Roberson SWilson JEet al. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020;24:176. [PMID: 32345343]  doi: 10.1186/s13054-020-02882-x
Rogers JPChesney EOliver Det al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7:611-27. [PMID: 32437679]  doi: 10.1016/S2215-0366(20)30203-0
Zalon MLSandhaus SKovaleski Met al. Hospitalized older adults with established delirium: recognition, documentation, and reporting. J Gerontol Nurs. 2017;43:32-40. [PMID: 27845806]  doi: 10.3928/00989134-20161109-01
Han JHZimmerman EECutler Net al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med. 2009;16:193-200. [PMID: 19154565]  doi: 10.1111/j.1553-2712.2008.00339.x
de la Cruz MFan JYennu Set al. The frequency of missed delirium in patients referred to palliative care in a comprehensive cancer center. Support Care Cancer. 2015;23:2427-33. [PMID: 25617070]  doi: 10.1007/s00520-015-2610-3
Trogrlic Zvan der Jagt MBakker Jet al. A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care. 2015;19:157. [PMID: 25888230]  doi: 10.1186/s13054-015-0886-9
Inouye SKvan Dyck CHAlessi CAet al. Clarifying confusion: the Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med. 1990;113:941-8. [PMID: 2240918]
van Velthuijsen ELZwakhalen SMWarnier RMet al. Psychometric properties and feasibility of instruments for the detection of delirium in older hospitalized patients: a systematic review. Int J Geriatr Psychiatry. 2016;31:974-89. [PMID: 26898375]  doi: 10.1002/gps.4441
Shi QWarren LSaposnik Get al. Confusion Assessment Method: a systematic review and meta-analysis of diagnostic accuracy. Neuropsychiatr Dis Treat. 2013;9:1359-70. [PMID: 24092976]  doi: 10.2147/NDT.S49520
Ringdal GIRingdal KJuliebø Vet al. Using the Mini-Mental State Examination to screen for delirium in elderly patients with hip fracture. Dement Geriatr Cogn Disord. 2011;32:394-400. [PMID: 22301509]  doi: 10.1159/000335743
Chester JGBeth Harrington MRudolph JLVA Delirium Working Group.. Serial administration of a modified Richmond Agitation and Sedation Scale for delirium screening. J Hosp Med. 2012;7:450-3. [PMID: 22173963]  doi: 10.1002/jhm.1003
Quispel-Aggenbach DWPHoltman GAZwartjes HAHTet al. Attention, arousal and other rapid bedside screening instruments for delirium in older patients: a systematic review of test accuracy studies. Age Ageing. 2018;47:644-53. [PMID: 29697753]  doi: 10.1093/ageing/afy058
De JWand AP. Delirium screening: a systematic review of delirium screening tools in hospitalized patients. Gerontologist. 2015;55:1079-99. [PMID: 26543179]  doi: 10.1093/geront/gnv100
Marcantonio ERNgo LHO’Connor Met al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med. 2014;161:554-61. [PMID: 25329203].  doi: 10.7326/M14-0865
Fick DMInouye SKGuess Jet al. Preliminary development of an ultrabrief two-item bedside test for delirium. J Hosp Med. 2015;10:645-50. [PMID: 26369992]  doi: 10.1002/jhm.2418
Shenkin SDFox CGodfrey Met al. Delirium detection in older acute medical inpatients: a multicentre prospective comparative diagnostic test accuracy study of the 4AT and the Confusion Assessment Method. BMC Med. 2019;17:138. [PMID: 31337404]  doi: 10.1186/s12916-019-1367-9
Khan BAZawahiri MCampbell NLet al. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research—a systematic evidence review. J Hosp Med. 2012;7:580-9. [PMID: 22684893]  doi: 10.1002/jhm.1949
Inouye SKBogardus ST JrCharpentier PAet al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340:669-76. [PMID: 10053175]
McKenzie JJoy A. Family intervention improves outcomes for patients with delirium: systematic review and meta-analysis. Australas J Ageing. 2020;39:21-30. [PMID: 31250961]  doi: 10.1111/ajag.12688
McDowell JAMion LCLydon TJet al. A nonpharmacologic sleep protocol for hospitalized older patients. J Am Geriatr Soc. 1998;46:700-5. [PMID: 9625184]
Tamrat RHuynh-Le MPGoyal M. Non-pharmacologic interventions to improve the sleep of hospitalized patients: a systematic review. J Gen Intern Med. 2014;29:788-95. [PMID: 24113807]  doi: 10.1007/s11606-013-2640-9
Khan ABoukrina OOh-Park Met al. Preventing delirium takes a village: systematic review and meta-analysis of delirium preventive models of care. J Hosp Med. 2019;14:E1-E7. [PMID: 31112492]  doi: 10.12788/jhm.3212
Rohatgi NLoftus PGrujic Oet al. Surgical comanagement by hospitalists improves patient outcomes: a propensity score analysis. Ann Surg. 2016;264:275-82. [PMID: 26764873]  doi: 10.1097/SLA.0000000000001629
Oh ESNeedham DMNikooie Ret al. Antipsychotics for preventing delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019;171:474-84. [PMID: 31476766].  doi: 10.7326/M19-1859
Nikooie RNeufeld KJOh ESet al. Antipsychotics for treating delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019;171:485-95. [PMID: 31476770].  doi: 10.7326/M19-1860
Girard TDExline MCCarson SSet alMIND-USA Investigators.. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018;379:2506-16. [PMID: 30346242]  doi: 10.1056/NEJMoa1808217
van den Boogaard MSlooter AJCBrüggemann RJMet alREDUCE Study Investigators.. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the REDUCE randomized clinical trial. JAMA. 2018;319:680-90. [PMID: 29466591]  doi: 10.1001/jama.2018.0160
Hshieh TTYue JOh Eet al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Intern Med. 2015;175:512-20. [PMID: 25643002]  doi: 10.1001/jamainternmed.2014.7779
Peritogiannis VBolosi MLixouriotis Cet al. Recent insights on prevalence and corelations of hypoactive delirium. Behav Neurol. 2015;2015:416792. [PMID: 26347584]  doi: 10.1155/2015/416792
Hosker CWard D. Hypoactive delirium. BMJ. 2017;357:j2047. [PMID: 28546253]  doi: 10.1136/bmj.j2047
Khan SGuerra CKhandji Aet al. Frequency of acute changes found on head computed tomographies in critically ill patients: a retrospective cohort study. J Crit Care. 2014;29:884. [PMID: 24927985]  doi: 10.1016/j.jcrc.2014.05.001
Theisen-Toupal JBreu ACMattison MLet al. Diagnostic yield of head computed tomography for the hospitalized medical patient with delirium. J Hosp Med. 2014;9:497-501. [PMID: 24733711]  doi: 10.1002/jhm.2198
Qu JChen YLuo Get al. Delirium in the acute phase of ischemic stroke: incidence, risk factors, and effects on functional outcome. J Stroke Cerebrovasc Dis. 2018;27:2641-7. [PMID: 30172676]  doi: 10.1016/j.jstrokecerebrovasdis.2018.05.034
Fong TGDavis DGrowdon MEet al. The interface between delirium and dementia in elderly adults. Lancet Neurol. 2015;14:823-32. [PMID: 26139023]  doi: 10.1016/S1474-4422(15)00101-5
Marchington KLCarrier LLawlor PG. Delirium masquerading as depression. Palliat Support Care. 2012;10:59-62. [PMID: 22329938]  doi: 10.1017/S1478951511000599
Lam CYTay LChan Met al. Prospective observational study of delirium recovery trajectories and associated short-term outcomes in older adults admitted to a specialized delirium unit. J Am Geriatr Soc. 2014;62:1649-57. [PMID: 25243679]  doi: 10.1111/jgs.12995
Serafim RBSoares MBozza FAet al. Outcomes of subsyndromal delirium in ICU: a systematic review and meta-analysis. Crit Care. 2017;21:179. [PMID: 28697802]  doi: 10.1186/s13054-017-1765-3
Caplan GACoconis JBoard Net al. Does home treatment affect delirium? A randomised controlled trial of rehabilitation of elderly and care at home or usual treatment (The REACH-OUT trial). Age Ageing. 2006;35:53-60. [PMID: 16239239]
Isaia GAstengo MATibaldi Vet al. Delirium in elderly home-treated patients: a prospective study with 6-month follow-up. Age (Dordr). 2009;31:109-17. [PMID: 19507055]  doi: 10.1007/s11357-009-9086-3
Egberts Avan der Craats STvan Wijk MDet al. Anticholinergic drug exposure is associated with delirium and postdischarge institutionalization in acutely ill hospitalized older patients. Pharmacol Res Perspect. 2017;5:e00310. [PMID: 28603629]  doi: 10.1002/prp2.310
By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel.. American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67:674-94. [PMID: 30693946]  doi: 10.1111/jgs.15767
Pandharipande PPEly EW. Humanizing the treatment of hyperactive delirium in the last days of life [Editorial]. JAMA. 2017;318:1014-5. [PMID: 28975287]  doi: 10.1001/jama.2017.11466
Herzig SJLaSalvia MTNaidus Eet al. Antipsychotics and the risk of aspiration pneumonia in individuals hospitalized for nonpsychiatric conditions: a cohort study. J Am Geriatr Soc. 2017;65:2580-6. [PMID: 29095482]  doi: 10.1111/jgs.15066
Park SYLee HB. Prevention and management of delirium in critically ill adult patients in the intensive care unit: a review based on the 2018 PADIS guidelines. Acute Crit Care. 2019;34:117-25. [PMID: 31723916]  doi: 10.4266/acc.2019.00451
Flükiger JHollinger ASpeich Bet al. Dexmedetomidine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis. Ann Intensive Care. 2018;8:92. [PMID: 30238227]  doi: 10.1186/s13613-018-0437-z
Skrobik YDuprey MSHill NSet al. Low-dose nocturnal dexmedetomidine prevents ICU delirium. A randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2018;197:1147-56. [PMID: 29498534]  doi: 10.1164/rccm.201710-1995OC
Ng KTShubash CJChong JS. The effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta-analysis with trial sequential analysis. Anaesthesia. 2019;74:380-92. [PMID: 30367689]  doi: 10.1111/anae.14472
Riker RRShehabi YBokesch PMet alSEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group.. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489-99. [PMID: 19188334]  doi: 10.1001/jama.2009.56
Jakob SMRuokonen EGrounds RMet alDexmedetomidine for Long-Term Sedation Investigators.. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307:1151-60. [PMID: 22436955]  doi: 10.1001/jama.2012.304
Yu AWu SZhang Zet al. Cholinesterase inhibitors for the treatment of delirium in non-ICU settings. Cochrane Database Syst Rev. 2018;6:CD012494. [PMID: 29952000]  doi: 10.1002/14651858.CD012494.pub2
Kostas TRZimmerman KMRudolph JL. Improving delirium care: prevention, monitoring, and assessment. Neurohospitalist. 2013;3:194-202. [PMID: 24198901]  doi: 10.1177/1941874413493185
Tan KMAustin BShaughnassy Met al. Falls in an acute hospital and their relationship to restraint use. Ir J Med Sci. 2005;174:28-31. [PMID: 16285335]
Rudolph JLArchambault EKelly BVA Boston Delirium Task Force.. A delirium risk modification program is associated with hospital outcomes. J Am Med Dir Assoc. 2014;15:957. [PMID: 25306293]  doi: 10.1016/j.jamda.2014.08.009
Schoen MWCull SBuckhold FR. False bed alarms: a teachable moment. JAMA Intern Med. 2016;176:741-2. [PMID: 27082247]  doi: 10.1001/jamainternmed.2016.1885
Nichani SFitterman NLukela Met alSociety of Hospital Medicine. Delirium and Dementia. 2017 Hospital Medicine Revised Core Competencies. J Hosp Med. 2017;12:S15-S18.  doi: 10.12788/jhm.3050
Saczynski JSMarcantonio ERQuach Let al. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012;367:30-9. [PMID: 22762316]  doi: 10.1056/NEJMoa1112923
Hshieh TTSaczynski JGou RYet alSAGES Study Group.. Trajectory of functional recovery after postoperative delirium in elective surgery. Ann Surg. 2017;265:647-53. [PMID: 27501176]  doi: 10.1097/SLA.0000000000001952
Khan BAPerkins AJGao Set al. The Confusion Assessment Method for the ICU-7 delirium severity scale: a novel delirium severity instrument for use in the ICU. Crit Care Med. 2017;45:851-7. [PMID: 28263192]  doi: 10.1097/CCM.0000000000002368
Jones RNCizginer SPavlech Let alBetter Assessment of Illness (BASIL) Study Group.. Assessment of instruments for measurement of delirium severity: a systematic review. JAMA Intern Med. 2019;179:231-9. [PMID: 30556827]  doi: 10.1001/jamainternmed.2018.6975
Tess AVMattison MLPLeo JRet al. Should this patient receive prophylactic medication to prevent delirium? Grand rounds discussion from Beth Israel Deaconess Medical Center. Ann Intern Med. 2018;168:498-505. [PMID: 29610916].  doi: 10.7326/M18-0388
Bush SHMarchington KLAgar Met al. Quality of clinical practice guidelines in delirium: a systematic appraisal. BMJ Open. 2017;7:e013809. [PMID: 28283488]  doi: 10.1136/bmjopen-2016-013809
Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium. SIGN publication no. 157. March 2019. Accessed at on 14 August 2020.
Australian Commission on Safety and Quality in Health Care. Delirium Clinical Care Standard. July 2016.
Devlin JWSkrobik YGélinas Cet 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:e825-e873. [PMID: 30113379]  doi: 10.1097/CCM.0000000000003299

Information & Authors


Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 173Number 76 October 2020
Pages: ITC49 - ITC64


Published online: 6 October 2020
Published in issue: 6 October 2020




Melissa L.P. Mattison, MD
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (M.L.M.)
CME Objective: To review current evidence for screening, prevention, diagnosis, treatment, and practice improvement of delirium.
Acknowledgment: The author thanks Edward R. Marcantonio, MD, author of the previous version of this In the Clinic.
Funding Source: American College of Physicians.
Disclosures: Dr. Mattison, ACP Contributing Author, has nothing to disclose. The form can be viewed at
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interests to disclose. Eliseo Guallar, MD, MPH, DrPH, Deputy Editor, Statistics, reports that he has no financial relationships or interests to disclose. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians. The patient information page was written by Monica Lizarraga from the Patient and Interprofessional Partnership Initiative at the American College of Physicians.
In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to

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