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delirium (acute confusional state)

A confusional state. (from the Latin de-lira 'off the path') Also see hypoactive delirium. Etiology: D - drugs*, dehydration E - electrolyte imbalances*, environment, endocrine* L - liver disease (encephalopathy), lungs (hypoxia) I - infection*, immune dysfunction, intracranial lesions, immobility R - retention, restraint I - ischemia*, intoxication, intestinal obstruction U - uremia M - myocardial disease*, metabolic abnormalities - Drugs & toxins: (see drugs commonly producing delirium) - Endocrine: - hypothyroidism, adrenal crisis, diabetic ketoacidosis, hypoglycemia - Electrolytes: - hyponatremia, hypocalcemia, hypercalcemia - Infection: - especially urinary tract infection* & pneumonia - Ischemia: - cerebral or cardiac ischemia, seizures - Retention (urinary retention or fecal impactation {constipation}) - Restraints & other tethers: IV lines, catheters, ECG leads - Cardiovascular disease: - myocardial infarction, arrhythmia, congestive heart failure - malignant hypertension - Metabolic abnormalities: - vitamin deficiencies - vitamin B12 deficiency - niacin deficiency (vitamin B3 deficiency) - thiamine deficiency (vitamin B1 deficiency) - consider withdrawal syndromes - alcohol withdrawal - benzodiazepine withdrawal [5] - SSRI withdrawal, especially paroxetine - uncontrolled pain, cancer pain [90,96] - sensory deprivation: hearing impairment, visual impairment [3] - sleep deprivation [3] - surgery * no association between asymptomatic bacteriuria & delirium [81] ==== risk factors for delirium ==== - see risk factors for delirium - see predisposing factors associated with delirium [88] - see precipitating factors associated with delirium [88] ==== drugs commonly producing delirium ==== - see drugs commonly producing delirium Epidemiology: 1) 20-50% of hospitalized elderly patients a) most common contributor to excess length of hospitalization [5] b) 75-90% of hospitalized patients with dementia [6] c) common in the intensive care unit [23] 2) 3/4 of patients admitted to the ICU with respiratory failure, cardiogenic shock, or septic shock experience delirium during their hospital stay [24] 3) often unrecognized a) fluctuating symptoms b) often attributed to dementia or psychiatric disorder - baseline assessment facilitates recognition c) may persist for months without correction of underlying cause Pathology: 1) relative cholinergic deficiency & dopaminergic excess 2) glucocorticoids may play a role 3) cognitive impairment, dehydration, hypoxia, infection, immobility, pain, poor nutrition, medication overuse,visual impairment, hearing impairment, & sleep deprivation contribute [18] Clinical manifestations: 1) rapid onset* (develops over hours to days) [6] 2) fluctuating with nocturnal exacerbation* a) 'sundowning' b) alteration in the sleep-wake cycle 3) inattention* (distinguishing feature of delirium) - impaired concentration 4) reduced level of consciousness# (inappropriately falls asleep) 5) impaired cognition# a) disorganized thinking b) learning & memory impairment (recent & remote) 6) perceptual disturbances - hallucinations, visual > auditory 7) psychosis & agitation a) delusions, generally paranoid & persecutional b) fleeting & poorly systematized thought processes 8) impaired orientation 9) disorders of affect a) emotional lability b) anxiety, depression, fear 10) personality changes 11) often incoherent speech; dysarthria may contribute 12) unpredictable psychomotor activity 13) asterixis, coarse tremor or myoclonus 14) underlying disease or drug toxicity 15) autonomic dysfunction a) tachycardia or bradycardia b) hypertension or hypotension c) flushing or pallor d) impairment of pupillary function e) abnormal control of sweating 16) delirium may persist more that 6 months [3,7,8,9] 17) confusion assessment method (CAM) is the best beside measure [16] - reciting months of the year backward has better sensitivity than confusion assessment method [36] - 3D-CAM based is a 3 minute version of CAM [37] * essential for diagnosis # either confirms diagnosis [3] Laboratory: 1) screening tests a) chemistries: - electrolytes, serum glucose, renal function tests - serum Mg+2, serum Ca+2, serum phosphate - liver function tests, plasma NH3, serum albumin - thyroid function tests - serum vitamin B12, serum folate b) hematology: - complete blood count (CBC) & differential - coagulation studies, PT, PTT - arterial blood gas (ABG) - serum CRP or ESR c) urinalysis & urine toxicology screen d) blood alcohol e) toxicology for ingested drugs f) therapeutic drug monitoring as indicated g) HIV testing 2) additional testing as indicated a) lumbar puncture with CSF analysis b) heavy metal screen Special laboratory: 1) electrocardiogram (EKG) 2) electroencephalogram a) generally, slowing or low-voltage activity - generalized EEG slowing in patients with altered mental status [73] b) triphasic waves may suggest hepatic disease c) periodic lateralizing epileptiform discharges suggest CNS infection d) 24 EEG monitor for non-convulsive status epilepticus - fluctuating mental status of unknown origin [3] - repeated episodes of staring, lethargy. nonresponsiveness 3) see Clinical manifestations: (above) for confusion assessment method (CAM) Radiology: 1) chest X-ray 2) neuroimaging as indicated, CT neuroimaging, MRI neuroimaging - diagnostic yield of head CT in delirium (emergency department or inpatient) is 13% - presence of focal neurologic deficit increases yield to 19% - yield higher in neurological ICUs (40%) - reserve for patients with falls associated with head injury or focal neurologic signs [3] Complications: 1) increased length of hospital stay [10] 2) increased mortality [11,17,40,95] (RR=1.71-2.19) 3) increased time spent on the ventilator, leading to increased incidence of ventilator associated pneumonia 4) increased rate of subsequent institutionalization (HR=2.41) [17] 5) delirium accelerates cognitive decline in patients with Alzheimer's disease - increased rate of cognitive decline for up to 5 years [34] - this seems in contrast to estimates of cognitive impairment due to postoperative delirium (see below) - it also seems a second episode of delirium would likely nullify any 5 year estimate based on a single episode 6) 10-fold increased risk of cognitive impairment at hospital discharge (HR=12.5) [17] - increased risk of dementia (HR=12.5) [95] - prolonged cognitive impairment after postoperative delirium [20] (6-12 months) 7) in ICU patients, a longer duration of delirium (5 days) independently predicts worse cognition at 3, 6 & 12 months, regardless of patient age or comorbidities [24, 40] 8) delirium is an independent risk factor for long-term cognitive decline in surgical & nonsurgical patients [76] 9) functional decline [5,54] - decline in activities of daily living [56] 10) increased mortality in ICU patients (RR=2.19) [40] 11) independent predictor of poor long-term outcomes, including cognitive decline & functional decline, institutionalization, & death in the elderly - cognitive decline & functional decline correlates with duration of delirium & persists at 6 months after hospital discharge [5,76] Differential diagnosis: 1) dementia 2) psychosis (see psychosis & agitation in the elderly) 3) transient global amnesia 4) aphasia 5) visual hallucinations due to structural lesions in the occipital lobes or cerebral peduncles 6) depression vs hypoactive delirium [5] 7) sudden onset suggests cerebrovascular disease or seizure - non-convulsive status epilepticus [63] - suspect if fluctuating mental status of unknown origin [3] 8) encephalopathy - Wernicke's encephalopathy (ophthalmoplegia, ataxia) 9) also see dementia vs delirium vs depression Management: === general === 1) urgent evaluation & management indicated [] 2) general in hospital guidelines (NICE) [5] a) identify patients at risk for delirium b) establish a multidisciplinary team to prevent & manage delirium - prevention is key [5] - multicomponent nonpharmacological interventions are effective in reducing incidence of delirium & preventing falls in the elderly [42,92] - once delirium occurs, multidisciplinary team of no benefit over standard care [5] c) avoid moving the patient between different rooms & wards d) ensure environment - appropriate lighting - orientational cues (clocks, calanders, name of facility) - reduce clutter & noise - bring familiar objects from home e) maintain hydration & avoid constipation f) vigilance for urinary retention - avoid unnecessary use of urinary catheter - antibiotics do not improve symptoms of delirium in elderly with pyuria or bacteriuria without systemic signs of infection or genitourinary symptoms [98] g) prevent & treat hypoxia & infections h) encourage mobility with appropriate assistance & supervision - early exercise & mobility shortens duration of delirium, shortens hospital stay & improves physical function & 1 years survival (GRS9) [5] i) assess & manage pain & sensory impairment - optimize pain control - vision assistance (eyeglasses) - hearing assistance (hearing aids) [3] j) review medications to determine whether any may increase risk of delirium k) promote & maintain nutrition & sleep hypgiene (allow uninterrupted sleep) l) frequent reorientation [3] 3) correction of underlying precipitating factor(s) - discontinue offending medications - remove unnecessary catheters - correct medication withdrawal syndromes (see Etiology:) - may need to rule out non-convulsive status epilepticus [3] 4) antidotes a) Narcan 0.1 mg/kg or 0.4-2.0 mg or more IV/IM/SC/ET b) consider flumazenil c) consider IV/IM thiamine if history of alcoholism, malnutrition, or chronic GI disorder associated with malabsorption, especially with nystagmus (ophthalmoplegia), & ataxia 5) withdrawal of non-essential medications 6) restraints may actually precipitate delirium 7) supportive care - close observation until delirium clears - individualized management of delirium precipitants & supportive strategies result in shorter duration of distressing delirium symptoms in palliative care patients than when risperidone or haloperidol is administered [64] === Pharmacology === 8) pharmacologic agents a) indications: - agitation not responding to non-pharmacologic measures - hypoactive delirium b) no drug is FDA-approved for prevention or treatment of delirium [3] - evidence does not support use of antipsychotics for prevention or treatment of delirium [65,66,72] - antipsychotic use is not associated with change in delirium duration, severity, or hospital or ICU length of stay, high heterogeneity among 19 studies [82] c) use low dose high potency antipsychotic [5] (not useful) [65,66,72] - avoid using in patients with Parkinson's disease or Lewy body dementia [35] - may worsen cognition - may result in neuroleptic malignant syndrome - NEJM Knowledge+ suggests high potency antipsychotic treatment of choice in patients who fail nonpharmacololgic intervemtions [91] d) antipsychotics, conventional (not useful) [65,66,72] - Haldol* 0.5-5 mg IV/IM/PO every 30-60 min - Haldol increases the duration of delirium in the ICU, albeit less so than lorazepam [5,27] - Haldol plus rivastigmine increases mortality in the ICU [32] - prophylactic haloperidol does not improve survival in ICU patients at 28 days [68] - neither haloperidol nor ziprasidone shortens duration of delirium in ICU patients [69] - only combination of haloperidol + lorazepam better than placebo [70] - better than haloperidol alone, rivastigmine, olanzapine, or dexmedetomidine - haloperidol 1.0-3.8 mg QD for 3-11 days associated with very-small dose-dependent improvement in survival of critically-ill patients with delirium (RR=0.91-0.95 at 28 days, 0.96-0.98 at 90 days) [80] - haloperidol no better than placebo for treatment of delirium in ICU patients [87] - drug of choice in hospitalized elderly [5,21] e) atypical antipsychotics: (not useful) [65,66,72] - may help control behavior when safety is a concern (MKSAP19) [3] - limited evidence of true efficacy in treating delirium [33] - use in controlling behavior rather than treating delirium [91] - respiridone, quetiapine, olanzapine - quetiapine preferred agent for patients with Parkinson's disease or Lewy body dementia [5,35] - may be as effective as haloperidol [33] - respiridone may be useful in surgical ICU [75] - neither haloperidol nor ziprasidone shortens duration of delirium in ICU patients [69] - all antipsychotics (atypical or conventional) associated with increased risk of mortality when used to treat psychosis, agitation & difficult behavior in the elderly f) compared with placebo, neither haloperidol nor ziprasidone decreases time that ICU patients remain alive without delirium or coma [14,69] - neither haloperidol nor ziprasidone has significant effects on cognition, function, quality-of-life, or psychological outcomes in critically ill patients with delirium [101] g) benzodiazepines - benzodiazepines should not be used to treat delirium in the absence of alcohol withdrawal, benzodiazepine withdrawal or seizures [3] - may exacerbate confusion in elderly patients [91] - lorazepam (Ativan) 0.5-1 mg every 1-2 hours IV/IM/PO - benzodiazpines increase the duration of delirium in the ICU [5,27] - coadministration of benzodiazepine with antipsychotic (haloperidol) may benefit elderly at end-of-life or with terminal cancer [3] h) opiates increase the duration of delirium inthe ICU [5,27] - morphine may be useful in ICU [75] i) dexmedetomidine for up to 1 week may shorten duration of delirium & mechanical ventilation time in ICU patients [43] - useful in both medical ICU & surgical ICU [75] j) ramelteon 8 mg QHS - reduces risk of delirium in hospitalized elderly (3% vs 32%) (small study 67 patients) [48] - useful for prevention in medical ICU [75] - may be useful for treatment of delirium (smaller study 10 patients) [49] h) discontinuation of previously used statin associated with increased risk of delirium [59] i) routine use of anticonvulsants for the prevention &/or treatment of delirium among older adults cannot be recommended [77] === Prognosis === 9) delirium is an independent predictor of poor long-term outcomes, including cognitive decline, functional decline, institutionalization, & death a) often leads to poor outcomes - persistent cognitive changes in > 20% [6] - accelerates cognitive decline in patients with Alzheimer's disease [31] - little is known about the relationship between delirium & cognitive trajectories in the elderly [31] b) increased risk of 1] prolonged hospitalization 2] loss of cognitive & functional abilities 3] mortality (25-40% within 30 days) [6] c) increased risk persists for 1-2 months following in-hospital delirium d) delirium in the emergency department predicts high 6 month mortality [15] e) dementia worsens prognosis - delirium is a marker of critical illness & increased vulnerability, not a cause of increased mortality [39] f) cognitive impairment during periods of delirium does not necessarily indicate dementia 10) patient education after delirium clears a) avoidance of precipitating factors b) disease-specific information === Prevention === 11) prevention is key a) more difficult to treat delirium than to prevent it b) see prevention of delirium [97] c) target risk factors [5] - cognitive impairment - sleep deprivation - immobility - visual impairment (eyeglasses) - orientation: calendar, clock, name of facility visible - dehydration - postoperative: keep hematocrit >= 30% - maintaining blood hemoglobin > 10 g/dL unlikely to affect risk of delirium [55] - dexmedetomidine may prevent postoperative delirium [61] but may not be beneficial after extubation === Guidelines === 12) guidelines for optimizing delirium care within an age-friendly health system with Hospital Elder Life Program (HELP) core interventions & the 4Ms [94] Notes: in ICU patients, - a longer duration of delirium (5 days) independently predicts worse cognition at 3 & 12 months,regardless of patient age or comorbidities - at 12 months, - 34% of patients with global cognition scores similar to scores seen in patients with moderate traumatic brain injury - 24% with scores similar to those seen in mild Alzheimer's disease [24] - a flexible family visitation policy, vs standard restricted visiting hours, does not significantly reduce the incidence of delirium [71] - Delirium Central [100] A Website that provides education, training, & resources about delirium for patients & families, clinicians, & researchers, https://www.deliriumcentral.org

Interactions

disease interactions

Related

confusion assessment method (CAM) dementia vs delirium vs depression diagnostic criteria for delirium (DSM III,IV) drugs commonly producing delirium prevention of delirium psychosis, agitation & difficult behavior in the elderly risk factors for delirium

Specific

hypoactive delirium postoperative delirium sundowning

General

altered mental status (AMS) metabolic encephalopathy; toxic encephalopathy

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1025-27
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009 Apr;5(4):210-20. Review. PMID: 19347026
  5. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004 - Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010 - Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  6. Mahler ME, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  7. Levkoff SE, Evans DA, Liptzin B, Cleary PD, Lipsitz LA, Wetle TT, Reilly CH, Pilgrim DM, Schor J, Rowe J. Delirium. The occurrence and persistence of symptoms among elderly hospitalized patients. Arch Intern Med. 1992 Feb;152(2):334-40. PMID: 1739363
  8. Rockwood K. The occurrence and duration of symptoms in elderly patients with delirium. J Gerontol. 1993 Jul;48(4):M162-6. PMID: 8315229
  9. Bergmann MA, Murphy KM, Kiely DK, Jones RN, Marcantonio ER. A model for management of delirious postacute care patients. J Am Geriatr Soc. 2005 Oct;53(10):1817-25. PMID: 16181185
  10. 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. Crit Care. 2005 Aug;9(4):R375-81. Epub 2005 Jun 1. PMID: 16137350
  11. Leslie DL, Zhang Y, Holford TR, Bogardus ST, Leo-Summers LS, Inouye SK. Premature death associated with delirium at 1-year follow-up. Arch Intern Med. 2005 Jul 25;165(14):1657-62. PMID: 16043686
  12. Fong TG et al. Delirium accelerates cognitive decline in Alzheimer disease. Neurology 2009 May 5; 72:1570. PMID: 19414723
  13. Brown LJE et al Cognitive visual perceptual deficits in patients with delirium. J Neurol Neurosurg Psychiatry 2009 Jun; 80:594. PMID: 19237384
  14. Girard TD et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: The MIND randomized, placebo- controlled trial. Crit Care Med 2010 Feb; 38:428. PMID: 20095068
  15. Han JH et al. Delirium in the emergency department: An independent predictor of death within 6 months. Ann Emerg Med 2010 Sep; 56:244. PMID: 20363527
  16. Wong CL et al. Does this patient have delirium? Value of bedside instruments. JAMA 2010 Aug 18; 304:779. PMID: 20716741
  17. 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 Jul 28; 304(4):443-451. PMID: 20664045
  18. O'Mahony R et al. Synopsis of the National Institute for Health and Clinical Excellence guideline for prevention of delirium. Ann Intern Med 2011 Jun 7; 154:746-751. PMID: 21646557
  19. Fong TG et al Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease Ann Intern Med. 19 June 2012;156(12):848-856 PMID: 22711077 http://annals.org/article.aspx?articleid=1183010
  20. Saczynski JS et al Cognitive Trajectories after Postoperative Delirium N Engl J Med 2012; 367:30-39 PMID: 22762316 http://www.nejm.org/doi/full/10.1056/NEJMoa1112923
  21. Campbell N, Boustani MA, Ayub A, et al. Pharmacological management of delirium in hospitalized adults- a systematic evidence review. J Gen Intern Med 2009; 24:848-853 PMID: 19424763
  22. Morandi A, Jackson JC. Delirium in the intensive care unit: A review. Neurol Clin 2011; 29:749-763 PMID: 22032658
  23. Schiemann A, Hadzidiakos D, Spies C. Managing ICU delirium. Curr Opin Crit Care. 2011 Apr;17(2):131-40 PMID: 21301333
  24. Pandharipande PP et al Long-Term Cognitive Impairment after Critical Illness. N Engl J Med 2013; 369:1306-131. October 3, 2013 PMID: 24088092 http://www.nejm.org/doi/full/10.1056/NEJMoa1301372 - Herridge M and Cameron JI Disability after Critical Illness N Engl J Med 2013; 369:1367-1369. October 3, 2013 PMID: 24088098 http://www.nejm.org/doi/full/10.1056/NEJMe1309482
  25. Young J, Murthy L, Westby M et al Diagnosis, prevention, and management of delirium: summary of NICE guidance. BMJ. 2010 Jul 28;341:c3704. PMID: 20667955
  26. Marcantonio ER, Bergmann MA, Kiely DK et al Randomized trial of a delirium abatement program for postacute skilled nursing facilities. J Am Geriatr Soc. 2010 Jun;58(6):1019-26 PMID: 20487083
  27. Pisani MA, Murphy TE, Araujo KL et al Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med. 2009 Jan;37(1):177-83. PMID: 9050611
  28. Rudolph JL1, Jones RN, Rasmussen LS et al Independent vascular and cognitive risk factors for postoperative delirium. Am J Med. 2007 Sep;120(9):807-13. PMID: 17765051
  29. Thomas C, Kreisel SH, Oster P et al Diagnosing delirium in older hospitalized adults with dementia: adapting the confusion assessment method to international classification of diseases, tenth revision, diagnostic criteria. J Am Geriatr Soc. 2012 Aug;60(8):1471-7. PMID: 22881707
  30. Yang FM, Marcantonio ER, Inouye SK et a; Phenomenological subtypes of delirium in older persons: patterns, prevalence, and prognosis. Psychosomatics. 2009 May-Jun;50(3):248-54. PMID: 19567764
  31. Popp J. Delirium and cognitive decline: more than a coincidence. Curr Opin Neurol. 2013 Dec;26(6):634-9 PMID: 24152819
  32. van Eijk MM, Roes KC, Honing ML et al Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double-blind, placebo-controlled randomised trial. Lancet. 2010 Nov 27;376(9755):1829-37. PMID: 21056464
  33. Ozbolt LB, Paniagua MA, Kaiser RM. Atypical antipsychotics for the treatment of delirious elders. J Am Med Dir Assoc. 2008 Jan;9(1):18-28. PMID: 18187109
  34. Gross AL, Jones RN, Habtemariam DA, et al. Delirium and long-term cognitive trajectory among persons with dementia. Arch Intern Med. 2012;172(17):1324-1331. PMID: 23403619
  35. Prescriber's Letter 21(6): 2014 Preventing and Treating Delirium in Inpatients Detail-Document#: 300612 (subscription needed) http://www.prescribersletter.com
  36. O'Regan NA et al. Attention! A good bedside test for delirium? J Neurol Neurosurg Psychiatry 2014 Oct; 85:1122 PMID: 24569688 http://jnnp.bmj.com/content/85/10/1122
  37. Marcantonio ER et 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 Oct 21; 161:554. PMID: 25329203 http://www.hospitalelderlifeprogram.org/
  38. Holroyd-Leduc JM, Khandwala F, Sink KM. How can delirium best be prevented and managed in older patients in hospital? CMAJ. 2010;182:265-270. PMID: 19687107
  39. Klein Klouwenberg PM et al. The attributable mortality of delirium in critically ill patients: Prospective cohort study. BMJ 2014 Nov 24; 349:g6652 PMID: 25422275 http://www.bmj.com/content/349/bmj.g6652
  40. Salluh JIF et al Outcome of delirium in critically ill patients: systematic review and meta-analysis. BMJ 2015;350:h2538 PMID: 26041151 http://www.bmj.com/content/350/bmj.h2538
  41. 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 Jan;41(1):263-306. PMID: 23269131
  42. Hshieh TT, Yue J, Oh E et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Intern Med. 2015;175(4):512-520 PMID: 25643002
  43. Reade MC et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: A randomized clinical trial. JAMA 2016 Apr 12; 315:1460. PMID: 26975647 - Ely EW, Pandharipande PP. The evolving approach to brain dysfunction in critically ill patients. JAMA 2016 Apr 12; 315:1455 PMID: 26976552
  44. Deschodt M, Braes T, Flamaing J et al Preventing delirium in older adults with recent hip fracture through multidisciplinary geriatric consultation. J Am Geriatr Soc. 2012 Apr;60(4):733-9. Epub 2012 Mar 16. PMID: 22429099
  45. Kalish VB, Gillham JE, Unwin BK. Delirium in older persons: evaluation and management. Am Fam Physician. 2014 Aug 1;90(3):150-8. Review. PMID: 25077720 Free Article
  46. Popp J, Arlt S. Prevention and treatment options for postoperative delirium in the elderly. Curr Opin Psychiatry. 2012 Nov;25(6):515-21. Review. PMID: 22992543
  47. Grover S, Mattoo SK, Gupta N. Usefulness of atypical antipsychotics and choline esterase inhibitors in delirium: a review. Pharmacopsychiatry. 2011 Mar;44(2):43-54. Review. PMID: 21394715
  48. Hatta K, Kishi Y, Wada K et l Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry. 2014 Apr;71(4):397-403 PMID: 24554232
  49. Tsuda A, Nishimura K, Naganawa E, Otsubo T, Ishigooka J. Successfully treated delirium in an extremely elderly patient by switching from risperidone to ramelteon. Psychiatry Clin Neurosci. 2013 Feb;67(2):130. PMID: 23438172 - Furuya M, Miyaoka T, Yasuda H et al Marked improvement in delirium with ramelteon: five case reports. Psychogeriatrics. 2012 Dec;12(4):259-62. PMID: 23279149 - Tsuda A, Nishimura K, Naganawa E, Otsubo T, Ishigooka J. Ramelteon for the treatment of delirium in elderly patients: a consecutive case series study. Int J Psychiatry Med. 2014;47(2):97-104. doi: 10.2190/PM.47.2.a. PMID: 25084796
  50. Inouye SK, Marcantonio ER, Metzger ED. Doing Damage in Delirium: The Hazards of Antipsychotic Treatment in Elderly Persons. Lancet Psychiatry. 2014 Sep 1;1(4):312-315. PMID: 25285270 Free PMC Article
  51. Barr J, Pandharipande PP. The pain, agitation, and delirium care bundle: synergistic benefits of implementing the 2013 Pain, Agitation, and Delirium Guidelines in an integrated and interdisciplinary fashion. Crit Care Med. 2013 Sep;41(9 Suppl 1):S99-115. Review. PMID: 23989099 - Pandharipande PP, Patel MB, Barr J. Management of pain, agitation, and delirium in critically ill patients. Pol Arch Med Wewn. 2014;124(3):114-23. Review. PMID: 24424616 Free Article
  52. Brummel NE, Girard TD. Preventing delirium in the intensive care unit. Crit Care Clin. 2013 Jan;29(1):51-65. Review. PMID: 23182527 Free PMC Article - 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 Feb;42(2):369-77. PMID: 24158172 Free PMC Article
  53. Davis DH, Muniz Terrera G, Keage H et al Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain. 2012 Sep;135(Pt 9):2809-16. PMID: 22879644 Free PMC Articleo
  54. Krogseth M, Wyller TB, Engedal K, Juliebo V. Delirium is a risk factor for institutionalization and functional decline in older hip fracture patients. J Psychosom Res. 2014 Jan;76(1):68-74. PMID: 24360144
  55. Gruber-Baldini AL, Marcantonio E, Orwig D et al Delirium outcomes in a randomized trial of blood transfusion thresholds in hospitalized older adults with hip fracture. J Am Geriatr Soc. 2013 Aug;61(8):1286-95. PMID: 23898894 Free PMC Article
  56. Liang CK, Chu CL, Chou MY et al Interrelationship of postoperative delirium and cognitive impairment and their impact on the functional status in older patients undergoing orthopaedic surgery: a prospective cohort study. PLoS One. 2014 Nov 17;9(11):e110339. PMID: 25402484 Free PMC Article
  57. Morandi A, McCurley J, Vasilevskis EE Tools to detect delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2012 Nov;60(11):2005-13. Review. PMID: 23039270 Free PMC Article
  58. Balas MC, Vasilevskis EE, Olsen KM et al Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/ mobility bundle. Crit Care Med. 2014 May;42(5):1024-36. PMID: 24394627 Free PMC Article
  59. Morandi A, Hughes CG, Thompson JL et al Statins and delirium during critical illness: a multicenter, prospective cohort study. Crit Care Med. 2014 Aug;42(8):1899-909. PMID: 24810528 Free PMC Article
  60. Page VJ, Davis D, Zhao XB Statin use and risk of delirium in the critically ill. Am J Respir Crit Care Med. 2014 Mar 15;189(6):666-73. PMID: 24417431 Free PMC Article
  61. Su X, Meng ZT, Wu XH et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: A randomised, double-blind, placebo- controlled trial. Lancet 2016 Aug 16; PMID: 27542303
  62. Inouye SK. Delirium in older persons. N Engl J Med 2006 03 16; 354:1157. PMID: 16540616
  63. NEJM Knowledge+. Question of the Week. Oct 11, 2016 http://knowledgeplus.nejm.org/question-of-week/1296/
  64. Agar MR, Lawlor PG, Quinn S et al Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care. A Randomized Clinical Trial. JAMA Intern Med. Published online December 5, 2016 PMID: 27918778 http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2588810
  65. Neufeld KJ, Yue J, Robinson TN, et al. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64(4):705 PMID: 27004732 Free PMC Article
  66. Siddiqi N, Harrison JK, Clegg A, et al. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2016; Issue 3. Art. No.: CD005563 PMID: 26967259
  67. Marcantonio ER Delirium in Hospitalized Older Adults. N Engl J Med 2017; 377:1456-1466. October 12, 2017. PMID: 29020579 http://www.nejm.org/doi/full/10.1056/NEJMcp1605501 - Rothaus C Delirium in Hospitalized Older Adults NEJM Resident 360. Oct 11, 2017 https://resident360.nejm.org/content_items/delirium-in-hospitalized-older-adults
  68. van den Boogaard M, Slooter AJC, Bruggemann RJM 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. Feb 20. PMID: 29466591 https://jamanetwork.com/journals/jama/fullarticle/2673149 - Delaney A, Hammond N, Litton E. Preventing Delirium in the Intensive Care Unit. JAMA. 2018;319(7):659-660 PMID: 29466573 https://jamanetwork.com/journals/jama/article-abstract/2673130
  69. Girard TD, Exline MC, Carson SS et al Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med. Oct 22, 2018 PMID: 30346242 PMCID: PMC6364999 Free full text https://www.nejm.org/doi/full/10.1056/NEJMoa1808217 - Bleck TP Dopamine Antagonists in ICU Delirium. N Engl J Med. Oct 22, 2018 PMID: 30346241 Free Article https://www.nejm.org/doi/full/10.1056/NEJMe1813382
  70. Wu YC, Tseng PT, Tu YK et al. Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: A network meta-analysis. JAMA Psychiatry 2019 Feb 27; [e-pub]. PMID: 30810723 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2726609 - Blazer DG. Pharmacologic intervention for the treatment and prevention of delirium: Looking beneath the modeling. JAMA Psychiatry 2019 Feb 27 PMID: 30810716 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2726605
  71. Rosa RG, Falavigna M, da Silva DB et al Effect of Flexible Family Visitation on Delirium Among Patients in the Intensive Care UnitThe ICU Visits Randomized Clinical Trial. JAMA. 2019;322(3):216-228. PMID: 31310297 https://jamanetwork.com/journals/jama/fullarticle/2738289 - Rose L, Muttalib F, Adhikari NKJ.. Psychological consequences of admission to the ICU: Helping patients and families. JAMA 2019 Jul 16; 322:213 https://jamanetwork.com/journals/jama/fullarticle/2738269 PMID: 31310279
  72. Oh ES, Needham DM, Nikooie R et al Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review. Ann Intern Med. 2019. Sept 3. PMID: 31476766 https://annals.org/aim/fullarticle/2749494/antipsychotics-preventing-delirium-hospitalized-adults-systematic-review - Nikooie R, Neufeld KJ, Oh ES et al Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review. Ann Intern Med. 2019. Sept 3. PMID: 31476770 https://annals.org/aim/fullarticle/2749495/antipsychotics-treating-delirium-hospitalized-adults-systematic-review - Marcantonio ER Old Habits Die Hard: Antipsychotics for Treatment of Delirium. Ann Intern Med. 2019. Sept 3. PMID: 31476768 https://annals.org/aim/article-abstract/2749505/old-habits-die-hard-antipsychotics-treatment-delirium
  73. Kimchi EY, Neelagiri A, Whitt W et al. Clinical EEG slowing correlates with delirium severity and predicts poor clinical outcomes. Neurology 2019 Sep 24; 93:e1260 PMID: 31467255
  74. Inouye SK Joining Forces against Delirium - From Organ-System Care to Whole-Human Care. N Engl J Med 2020;382:499-501. Feb 6. PMID: 32023371 https://www.nejm.org/doi/full/10.1056/NEJMp1910499
  75. Kim MS, Rhim HC, Park A et al. Comparative efficacy and acceptability of pharmacological interventions for the treatment and prevention of delirium: A systematic review and network meta-analysis. J Psychiatr Res 2020 Jun; 125:164. Review. PMID: 32302794 https://www.sciencedirect.com/science/article/abs/pii/S0022395619312877
  76. Goldberg TE et al. Association of delirium with long-term cognitive decline: A meta-analysis. JAMA Neurol. 2020 Jul 13:e202273. PMID: 32658246 https://jamanetwork.com/journals/jamaneurology/fullarticle/2768000
  77. Bhattacharya G, Gupta A, Joshi P et al Is there evidence for using anticonvulsants in the prevention and/or treatment of delirium among older adults? Am J Geriatric Psychiatry 2021 April. 29(4): S136-S139 https://www.sciencedirect.com/science/article/abs/pii/S1064748121001573
  78. Wikipedia: Delirium https://en.wikipedia.org/wiki/Delirium
  79. Talebraza S et al Geriatrics Evaluation & Management Tools American Geriatrics Society. 2021 https://geriatricscareonline.org/ProductAbstract/geriatrics-evaluation-management-tools/B007/
  80. Duprey MS, Devlin JW, van der Hoeven JG et al Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults. Crit Care Med. 2021;49(8):1303-1311. PMID: 33861548 PMCID: PMC8282692 (available on 2022-08-01) https://www.medscape.com/viewarticle/955328
  81. Krinitski D, Kasina R, Kloppel S, Lenouvel E Associations of delirium with urinary tract infections and asymptomatic bacteriuria in adults aged 65 and older: A systematic review and meta-analysis. J Am Geriatr Soc. 2021. Aug 27 PMID: 34448496 https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.17418
  82. Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM Antipsychotics for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64(4):705-714 PMID: 27004732 PMCID: PMC4840067 Free PMC article
  83. Burry L, Mehta S, Perreault MM, et al. Antipsychotics for treatment of delirium in hospitalized non-ICU patients. Cochrane Database Syst Rev. 2018 Jun; 2018(6): CD005594. PMID: 29920656 PMCID: PMC6513380 Free PMC article https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005594.pub3/full
  84. Bush SH, Tierney S, Lawlor PG. Clinical assessment and management of delirium in the palliative care setting. Drugs. 2017;77(15):1623-1643 PMID: 28864877 PMCID: PMC5613058 Free PMC article https://link.springer.com/article/10.1007/s40265-017-0804-3
  85. Geriatric Medicine Research Collaborative. Delirium is prevalent in older hospital inpatients and associated with adverse outcomes: results of a prospective multi-centre study on World Delirium Awareness Day. BMC Med. 2019;17(1):229. PMID: 31837711 PMCID: PMC6911703 Free PMC article https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1458-7 - Shenkin SD, Fox C, Godfrey M, et 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(1):138 PMID: 31337404 PMCID: PMC6651960 Free PMC article https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1367-9
  86. Oh ES, Fong TG, Hshieh TT et al. Delirium in older persons: advances in diagnosis and treatment. JAMA. 2017;318(12):1161-1174 PMID: 28973626 PMCID: PMC5717753 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2654826
  87. George J Haloperidol for ICU Delirium Misses on Hard Endpoints. No difference from placebo on composite outcome in randomized trial. MedPage Today October 27, 2022 https://www.medpagetoday.com/neurology/generalneurology/101460 - Andersen-Ranberg NC, Poulsen LM, Perner A et al Haloperidol for the Treatment of Delirium in ICU Patients. N Eng J Med. 2022. Oct 26. PMID: 36286254 https://www.nejm.org/doi/full/10.1056/NEJMoa2211868
  88. Ormseth CH, LaHue SC, Oldham MA et al Predisposing and Precipitating Factors Associated With Delirium. A Systematic Review. JAMA Netw Open. 2023;6(1):e2249950 PMID: 36607634 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800112
  89. Akhtar H et al. Diagnostic yield of CT head in delirium and altered mental status- A systematic review and meta-analysis. J Am Geriatr Soc 2023 Mar; 71:946. PMID: 36434820 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18134
  90. Centeno C, Sanz A, Bruera E. Delirium in advanced cancer patients. Palliat Med. 2004 Apr;18(3):184-94. PMID: 15198131 Review.
  91. NEJM Knowledge+ Psychiatry
  92. Musick H Effectiveness of Non Pharmacological Interventions in Preventing Delirium Among Older Adults. Annals of Long-Term Care. August 14, 2023 https://www.hmpgloballearningnetwork.com/site/altc/news/effectiveness-non-pharmacological-interventions-preventing-delirium-among-older - Zhao Q, Liu S, Zhao H, et all. Non-pharmacological interventions to prevent and treat delirium in older people: An overview of systematic reviews. Intnl Jour of Nursing Studies. August 9, 2023 PMID: 37826889
  93. Mattison MLP. Delirium. Ann Intern Med. 2020;173:ITC49-ITC64. PMID: 33017552.
  94. Kwak MJ, MS, Inouye SK, Fick DM et al Optimizing delirium care in the era of Age-Friendly Health System J Am Geriatr Soc. 2024 Jan;72(1):14-23 PMID: 37909706 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18631
  95. Gordon EH, Ward DD, Xiong H, Berkovsky S, Hubbard RE. Delirium and incident dementia in hospital patients in New South Wales, Australia: Retrospective cohort study. BMJ 2024 Mar 27; 384:e077634 PMID: 38537951 PMCID: PMC10966895 Free PMC article https://www.bmj.com/content/384/bmj-2023-077634
  96. Sampson EL, West E, Fischer T. Pain and delirium: mechanisms, assessment, and management. Eur Geriatr Med. 2020 Feb;11(1):45-52. PMID: 32297242 https://link.springer.com/article/10.1007/s41999-019-00281-2
  97. Herling SF, Greve IE, Vasilevskis EE et al Interventions for preventing intensive care unit delirium in adults. Cochrane Database Syst Rev. 2018 Nov 23;11(11):CD009783. PMID: 30484283 PMCID: PMC6373634 Free PMC article. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009783.pub2/full
  98. Stall NM, Kandel C, Reppas-Rindlisbacher C, et al. Antibiotics for delirium in older adults with pyuria or bacteriuria: A systematic review. J Am Geriatr Soc. 2024 Jun 19. PMID: 38895992 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18964
  99. Alagiakrishnan K et al Delirium Medscape. 2024. April 15 https://emedicine.medscape.com/article/288890-overview
  100. Delirium Central Dr. Sharon K. Inouye Aging Brain Center team at the Marcus Institute for Aging Research Harvard Medical School affiliate. https://www.deliriumcentral.org/
  101. Mart MF, Boehm LM, Kiehl AL et al Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2024 Aug;12(8):599-607. PMID: 38701817 Clinical Trial.