Posted on August 5, 2008 in by admin6 Comments »

Incidence

The incidence in the UK in ventilated critically ill patients is 55% to 69%. This audit data has been collected from a number of centres and presented as poster presentations at Intensive Care conferences. Refs.

The incidence is less in less sick patients. So, for example the incidence at Watford General Hospital, a typical UK district and general HDU/ITU using a validated screening tool, the CAM-ICU, the overall incidence is 28%, if you exclude elective post-operative patients it is 38% and in ventilated patients only it is 63%.

Internationally the incidence varies from 20% to 50% in lower-severity patients to 60% up to 80% in ventilated patients with APACHE scores greater than 25. Refs.

Risk Factors

Patients get delirium or not depending on how vulnerable they are. How many predisposing factors do they have? On top of which are added one or more precipitating factors that trigger the delirium.

For instance a patient who has pre-existing cognitive impairment is likely to become delirious with a urinary tract infection. A patient with more than 3 risk factors has a 60% chance of developing delirium – critically ill patients can have up to 10.

The single most important modifiable risk factor in critical care is the use of sedative drugs. See management.

Outcomes

Death

Delirium is an independent predictor of death in intensive care patients. This means after adjusting for pre-existing co morbidity and cognitive impairment, ICU diagnosis AND severity of illness delirious patients are 2 to 3 times more likely to die. Each additional day spent in delirium is associated with a 20% increase risk of prolonged hospitalization and a 10% increased risk of death.

ICU delirium is predictive of a 3-fold higher reintubation rate and over 10 additional days in the hospital and all the financial and human costs this incurs.

Dementia

Investigations into the relationship between delirium and long-term cognitive outcomes have consistently demonstrated a link. Emerging data indicates delirium may lead to or accelerate dementia. One third of ventilated ICU patients have long-term cognitive impairment persisting at 3 years. MMSE scores of delirious patients are 5 points lower than patients without delirium one year later after adjusting for co-morbidity and severity of illness. In practice? Your patient after leaving ITU is unable to return to anything like the life they enjoyed before.

References

History and Classification

  • Delirium, A Syndrome of Cerebral Insufficiency.
    GL Engel and J Romano. Journal of Chronic Diseases 1959; 9: 260-277
  • Intensive Care Syndrome. A Dangerous Misnomer.
    BE McGuire, CJ Basten, CJ Ryan and J Gallagher. Archives of Internal Medicine 2000; 160: 906-909.
  • Delirium as a disorder of consciousness.
    R Bhat and K Rockwood. Journal of Neurology, Neurosurgery and Psychiatry. 2007; 78: 1167-1170
  • Defining delirium for the International Classification of Diseases.
    DJ Meagher, AMJ MacLullich and JV Laurila. Journal of Psychosomatic Research. 2008; 65: 207-214
  • American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders. 4th edition, text revision. Washington DC: American Psychiatric Association, 2000.
  • Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.
    A Morandi, P Pandharipande, Trabucchi et al. Intensive Care Medicine 2008; 34: 1907-15
Prevalence and Risk Factors
Critical Care
  • Delirium in the intensive care unit: occurrence and clinical course in older patients.
    L McNicoll, MA Pisani, Y Zhang et al JAGS 2003; 51: 591-8
  • Delirium in an intensive care unit: a study of risk factors.
    M-J Dubois, N Bergeron, M Dumont et al. Intensive Care Medicine 2001; 27: 1297-1304.
  • Incidence, risk factors and consequences of ICU delirium.
    S Ouimet, BP Kavanagh, SB Gottfried and Y Skrobik Intensive Care Medicine 2007; 33: 66-73
  • Prevalence and Risk factors for Development of Delirium in Surgical and Trauma Intensive Care Patients.
    The Journal of Trauma. 2008; 65: 34-41
  • Characteristics associated with delirium in older patients in a medical intensive care unit.
    MA Pisani, TE Murphy, PH Van Ness et al. Archives of Internal Medicine 2007; 167: 1629-34
  • Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients.
    S-M Lin, C-D Huang, C-Y Liu et al. Journal of Critical Care 2008; 23: 372-9
  • Risk factors for delirium after major trauma.
    EM Angles, TN Robinson, WL Biffl et al. The American Journal of Surgery 2008; 196:864-70
  • Delirium as detected by the CAM-ICU predicts restraint use among mechanically ventilated patients.
    ST Micek, NJ Anand, BR Laible et al. Critical Care Medicine 2005; 33: 1260-5
  • Sleep and delirium in ICU patients: a review of mechanisms and manifestations.
    MI Figueroa-Ramos, CM Arroyo-Novoa, KA Lee et al. Intensive Care Medicine 2009; 35: 781-795
Medical Care
  • The course of delirium in older medical inpatients.
    J McCusker, M Cole, M Dendukuri et al. Journal of General Internal Medicine 2003; 18: 696-704
  • Predisposing and Precipitating factors for delirium in hospitalized older patients.
    SK Inouye. Dementia and Geriatric Cognitive Disorders 1999; 10: 393-400
  • Precipitating factors for delirium in hospitalized elderly persons.
    SK Inouye and PA Charpentier JAMA 1996; 275: 852-7
  • A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics.
    SK Inouye, CM Viscoli, RI Horwitz et al. Annals of Internal Medicine 1993; 119: 474-481.
  • Predicting delirium in elderly patients: development and validation of risk stratification model.
    ST O’Keefe and JN Lavan. Age and Ageing 1996; 25: 317-21
  • Occurrence and outcome of delirium in medical in-patients: a systematic literature review.
    N Siddiqui, AO House and J Holmes Age and Ageing 2006; 35: 350-364
  • Delirium risk factors in elderly hospitalized patients.
    M Elie, MG Cole, FJ Primeau and R Bellavance Journal of General Internal Medicine. 1998; 13: 204-212
  • Persistent delirium in older hospital patients: a systematic review of frequency and prognosis.
    MG Cole, A Ciampi, E Belzile and L Zhong Age and Ageing 2009; 38: 19-26
  • The course of delirium in acute stroke.
    J McManus, R Pathansali, H Hassan et al. Age and Ageing 2009; 38: 385-9
  • Delirium Symptoms in Post-Acute Care: Prevalent, Persistent and associated with poor functional recovery.
    ER Marcantonio, SE Simon, MA Bergmann et al. Journal of the American Geriatric Society 2003; 51: 4-9.
  • Occurrence and outcome of delirium in medical in-patients: a systematic literature review.
    N Siddiqui, AO House and J Holmes Age and Ageing 2006; 35: 350-364
  • Risk factors for delirium at discharge. Development and Validation of Predictive Model.
    SK Inouye, Y Zhang, RN Jones et al Archives of Internal Medicine 2007; 167: 1406-13
  • Environmental risk factors for delirium in hospitalized older people.
    J McCusker, M Cole, M Abrahamowicz et al JAGS 2001; 49: 1327-34
  • Characteristics associated with delirium persistence among newly admitted post-acute facility patients.
    DK Kiely, MA Bergmann, RN Jones et al. Journal of Gerontology 2004; 59: 344-49
  • Persistent delirium in older hospital patients: a systematic review of frequency and prognosis.
    MG Cole, A Ciampi, E Belzile and L Zhong Age and Ageing 2009; 38: 19-26
Post-operative patients
  • Postoperative delirium in the elderly.
    ST O’Keefe and A Ni Chonchubhair. British Journal of Anaestheisa 1994; 73: 673-687
  • Postoperative delirium in the elderly, risk factors and outcomes.
    TN Robinson, CD Raeburn, ZV Tran et al. Annals of Surgery 2009; 249: 173-178.
  • Risk factors and prediction of postoperative delirium in elderly hip-surgery patients: implementation and validation of medical risk factor model.
    KJ Kalisvaart, R Vreeswijk, JFM de Jonghe et al. JAGS 2006; 54: 817-22
  • Executive function and depression as independent risk factors for postoperative delirium.
    PJ Smith, DK Attix, C Weldon et al. Anesthesiology 2009; 110: 781-7
  • Delirium after abdominal surgery at a surgical ward with a high standard of delirium care: incidence, risk factors and outcomes.
    B Koebrugge, HL Koek, RJ van Wensen. Digestive Surgery 2009; 26: 63-68
  • Falls in general hospital: Association with delirium, advanced age and specific surgical procedures.
    BE Lakatos, V Capasso, MT Mitchell et al. Psychosomatics 2009; 50: 218-226
  • Incidence of and Preoperative predictors for delirium after cardiac surgery.
    RC van der Mast, WW van den Broek, D Fekkes et al. Journal of Psychosomatic Research 1999; 46: 479-483
  • Incidence and risk factors for delirium and other adverse outcomes in older adults after coronary artery bypass graft surgery.
    DB Rolfson, JE McElhaney, K Rockwood et al. Canadian Journal of Cardiology 1999; 15: 771-776
  • Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery.
    JL Rudolph, RN Jones, SE Levkoff et al. Circulation 2009; 119: 229-236.
  • Preoperative predictors of delirium after cardiac surgery: a preliminary study.
    J Kazmierski, M Kowman, M Banach et al. General Hospital Psychiatry 2006; 28: 536-8
  • Is preoperative anxiety and depression associated with onset of delirium after cardiac surgery in older patients? A prospective cohort study.
    E Detroyer, F Dobbels, E Verfaillie et al. JAGS 2008; 56: 2278-84
  • Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery.
    J Bucerius, JF Gummert, MA Borger et al. The Journal of Thoracic and Cardiovascular Surgery. 2004; 127: 57-64
Miscellaneous
  • Development of delirium: a prospective cohort study in a community hospital.
    NJ Martin, MJ Stones, JE Young and M Bedard International Psychogeriatrics 2000; 12: 117-27
  • Delirium in nursing home patients seen in the emergency department.
    JH Han, A Morandi, EW Ely et al. JAGS 2009; 57: 889-94
Drugs and Delirium
  • Association between psychoactive medications and delirium in hospitalized patients: a critical review.
    J-D Gadreau, P Gagnon, M-A Roy et al. Psychosomatics 2005; 46: 302-316
  • Benzodiazepine and opioid use and the duration of intensive care delirium in an older population.
    MA Pisani, TE Murphy, KLb Araujo et al. Critical Care Medicine 2009; 37: 177-183
  • Lorazepam in an independent risk factor for transitioning to delirium in intensive care unit patients.
    P Pandharipande, A Shintani, J Peterson et al. Anesthesiology 2006; 104: 21-6
  • Remifentanil reduces the incidence of post-operative delirium.
    FM Radtke, M Franck, M Lorenz et al. Journal of Internal Medical Research 2010; 38: 1225-32
  • Relationship between pain and opiod analgesics on the development of delirium following hip fracture.
    Journal of Gerontology: medical sciences. 2003; 58: 76-81
  • Psychoactive medications and risk of delirium in hospitalized cancer patients
    J-D Gadreau, P Gagnon, F Harel et al. Journal of Clinical Oncology 2005; 23: 6712-18
  • Is dopamine administration possibly a risk factor for delirium?
    BR Sommer, LC Wise, HC Kraemer. Critical Care Medicine 2002; 30: 1508-11
  • Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care.
    RM Venn, MD Karol and RM Grounds. British Journal of Anaesthesia 2002; 88: 669-75
  • Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients. The MENDS randomized controlled trial.
    PP Pandharipande, BT Pun, DL Herr et al. JAMA 2007; 298: 2644-53
  • Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients.
    Y Shehabi, RR Riker, PM Bokesch et al. Critical Care Medicine 2010 38: 2311-18
  • Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal.
    J Darrouj, N Puri, E Prince et al. The Annals of Pharmacotherapy 2008; 42: 1703-5
  • 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.
    MM van Eijk, KC Roes, ML Honing et al. Lancet 2010 Nov 4

Delirium subtypes

  • An empirical study of delirium subtypes.
    B Liptzin and SE Levkoff. British Journal of Psychiatry 1992; 161: 843-5
  • The delirium subtypes: a review of prevalence, phenomenology, pathophysiology, and treatment response.
    D Stagno, C Gibson and W Bretibart. Palliative and Supportive Care 2004; 2: 171-9
  • Clinical subtypes of delirium in the elderly.
    ST O’Keefe Dementia and Geriatric Cognitive Disorders 1999; 10: 380-5
  • Etiologic and Outcome profiles in hypoactive and hyperactive subtypes of delirium.
    V Camus, R Gonthier, G Dubos et al. Journal of Geriatric Psychiatry and Neurology 2000; 13: 38-42
  • Delirium and its motoric subtypes: a study of 614 critically ill patients.
    JF Peterson, BT Pun, RS Dittus et al. JAGS 2006; 54: 479-84
  • Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes.
    JC Woods, LC Mion, JT Connor et al. Intensive Care Medicine 2004; 30: 1066-72
  • Relationship between symptoms and motoric subtype of delirium.
    DJ Meagher, D O’Hanlon, E O’Mahony et al The Journal of Neuropsychiatry and Clinical Neurosciences 2000; 12: 51-6
  • Motor symptoms in 100 patients with delirium versus control subjects: comparison of subtyping methods.
    DJ Meagher, M Moran, B Raju et al Psychosomatics 2008; 49: 300-8
  • Motion analysis in delirium: a discrete approach in determining physical activity for the purposes of delirium motoric subtyping.
    A Godfrey, R Conway, M Leonard et al. Medical Engineering and Physics 2010; 32: 101-110
  • A new data-based motor subtype schema for delirium.
    D Meagher, M Moran, B Raju et al. The Journal of Neuropsychiatry and Clinical Neurosciences 2008; 20: 185-93
  • The overlap syndrome of depression and delirium in older hospitalized patients.
    JL Givens, RN Jones and SK Inouye. JAGS 2009; 57: 1347-53
  • Subsyndromal delirium in the ICU :evidence for a disease spectrum.
    S Ouimet, R Riker, N Bergeron et al. Intensive Care Medicine 2007; 33: 1007-13
Outcomes
  • Delirium as a predictor of mortality in mechanically ventilated patients in the Intensive Care Unit.
    EW Ely, A Shintani, B Truman et al. JAMA 2004; 291: 1753-62
  • The impact of delirium on the survival of mechanically ventilated patients.
    S-M Lin, C-Y Lui, C-H Wang et al. Critical Care Medicine 2004; 32: 2254-9
  • Outcomes associated with delirium in older patients in surgical ICUs.
    M Balas, MB Happ, W Yang. Chest 2009; 135: 18-25
  • The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients.
    I Lat, W McMillian, S Taylor et al. Critical Care Medicine 2009; 37: 1898-1905
  • Long-term Neurocognitive function after critical illness.
    R Hopkins and JC Jackson. Chest 2006; 130: 869-878
  • Brain atrophy and cognitive impairment in survivors of acute respiratory distress syndrome.
    R Hopkins, S Gale and L Weaver. Brain Injury 2006; 20: 263-71
  • Loss of IQ in the ICU brain injury without the insult.
    ML Gunther, JC Jackson and EW Ely. Medical Hypotheses 2007; 69: 1179-82
  • Delirium as a predictor of long-term cognitive impairment in survivors of critical illness.
    TD Girard, JC Jackson, PP Pandharipande et al. Critical Care Medicine 2010; 38: 1513-191
  • Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients.
    JWW Thomason, A Shintani, JF Peterson et al. Critical Care 2005; 9: R375-R381
  • The impact of delirium in the intensive care unit on hospital length of stay.
    EW Ely, S Gautam, R Margolin. Intensive Care Medicine 2001;27L1892-1900
  • Costs associated with delirium in mechanically ventilated patients.
    EB Milbrandt, S Deppen, PL Harrison et al. Critical Care Medicine 2004; 32: 955-62
  • Agitation in the critically ill patient: A marker of health or a plea for treatment?
    W Schweickert and JB Hall. Critical Care Medicine 2005; 33: 263-5
  • Does delirum contribute to poor hospital outcomes?
    SK Inouye, JT Rushing, MD Foreman. Journal of General Internal Medicine 19989; 13: 234-242
  • The 6 and 12 month outcomes of older medical patients who recover from delirium.
    MG Cole, Y You, J McCusker et al. International Journal of Geriatric Psychiatry 2008; 23: 301-7
  • Delirium predicts 12-month mortality.
    J McCusker, M Cole, M Abrahamowicz and F Primeau. Archives of Internal Medicine 2002l 162L 457-63
  • Does delirium increase hospital stay?
    J McCusker, MG Cole, N Dendukuri and E Belzile. JAGS 2003;51: 1539-46
  • Delirium accelerates cognitive decline in Alzheimer disease.
    TG Fong, RN Jones, P Shi et al. Neurology 2009; 72: 1570-1575
  • Hospital use, institutionalisation and mortality associated with delirium.
    E Eeles, RE Hubbard, SV White et al. Age and Ageing 2010 39: 470-75
  • Long-term Neurocognitive function after critical illness.
    R Hopkins and JC Jackson. Chest 2006; 130: 869-878
  • The risk of dementia and death after delirium.
    K Rockwood, S Cosway, D Carver. Age and Ageing 1999; 28: 551-6
  • Older adults discharged from the hospital with delirium: 1 year outcomes.
    GJ McAvay, PH Van Ness, ST Bogardus et al. JAGS 2006; 54: 1245-50
  • Delirium in older medical patients and subsequent cognitive and functional status: a prospective study.
    J McCusker, M Cole, N Dendukuri et al. CMAJ 2001; 165: 575-83
  • Association between delirium resolution and functional recovery among newly admitted postacute facility patients.
    DK Kiely, RN Jones, BA Bergmann et al Journal of Gerontology 2006; 61: 204-8
  • The 6 and 12 month outcomes of older medical inpatients who recover from subsyndromal delirium.
    MG Cole, J McCusker, A Ciampi and E Belzile. JAGS 2008; 56:2093-99
  • Effect of postoperative delirium on outcome after hip fracture.
    DM Edlestein, GB Aharonoff, A Karp et al. Clinical Orthopaedics and related Research. 2003; 422: 195-200
  • The long-term cognitive and functional outcomes of postoperative delirium after cardiac surgery.
    S Koster, AG Hensens, J van der Palen. Annals of Thoracic Surgery 2009; 87: 1469-74
  • Adverse outcomes of Geriatric Patients undergoing abdominal surgery who are at high risk of delirium.
    S Ganai, F Lee, A Merrill. Archives of Surgery 2007; 142: 1072-78
  • Delirium in older emergency department patients discharged home: effect on survival.
    R Kakuma, G Galbaud du Fort, L Arsenault et al. JAGS 2003; 51: 443-50
  • Long-term cognitive outcome of delirium in elderly hip surgery patients.
    MG Kat, R Vreeswijk, JF de Jonghe et al. Dementia and Geriatric Cognitive Disorders 2008; 26: 1-8
  • High risk of cognitive and functional decline after postoperative delirium.
    H Bickel, R Gradinger, E Kochs and H Forstl. Dementia and Geriatric Cognitive Disorders 2008; 26:26-31
  • Association between delirium resolution and functional recovery among newly admitted postacute facility patients.
    DK Kiely, RN Jones, BA Bergmann et al Journal of Gerontology 2006; 61: 204-8
  • Posttraumatic stress disorder in general intensive care unit survivors: a systematic review.
    DS Davydow, JM Gifford, SV Desai et al. General Hospital Psychiatry 2008 30;421-34
  • Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study.
    T Girard, A Shintani, JC Jackson et al. Critical Care 2007;11: R28
  • Precipitants of post-traumatic stress disorder following intensive care: a hypothesis generating study of diversity of care.
    C Jones, C Backman, M Capuzzo et al. Intensive Care Medicine 2007; 33: 978-985.
Delirium Screening
  • A critique of instruments and methods to detect, diagnose and rate delirium.
    MJ Smith, WS Breitbart and MM Platt. Journal of Pain and Symptom Management. 1995; 10: 35-77
  • Nurses recognition of delirium and its symptoms.
    SK Inouye, MD Foreman, LC Mion et al. Archives of Internal Medicine 2001; 161: 2467-73
  • Clarifying confusion: The Confusion Assessment Method.
    SK Inouye, CH van Dyck, CA Alessi et al. Annals of Internal Medicine 1990; 113: 941-8
  • Detection of delirium by bedside nurses using the confusion assessment method.
    J Lemiengre, T Nelis, E Joosten et al. JAGS 54; 685-9
  • Confusion Assessment Method in the diagnostics of delirium among aged hospital patients: Would it serve better in screening than as a diagnostic instrument?
    JV Laurila, KH Pitkala. TE Strandberg and RS Tilvis. International Journal of Geriatric Psychiatry 2002;17: 1112-9
  • An empirical study of different diagnostic criteria for delirium among elderly medical inpatients.
    MG Cole, N Dendukuri, J McCusker and L Han. Journal of Neuropsychiatry and Clinical Neurosciences. 2003;15: 200-7
  • Validation of the Delirium Rating Scale-Revised-98: Comparison with the Delirium Rating Scale and the Cognitive Test for Delirium.
    PT Trzepacz, D Mittal, R Torres. The Journal of Neuropsychiatry and Neurosciences 2001; 13: 229-242
  • Abbreviated cognitive test for delirium.
    RP Hart, AM Best, C Sessler and JL Levenson. Journal of Psychosomatic Research 1997; 43: 471-2?
  • Occurrence of delirium is severely underestimated in the ICU during daily care.
    PE Spronk, B Riekerk, J Hofhuis and JH Rommes. Intensive Care Medicine 2009;35: 1276-80
  • Validation of a cognitive test for delirium in medical ICU patients.
    RP Hart, JL Levenson, C Sessler et al. Psychosomatics 1996; 37: 533-46
  • Evaluation of delirium in critically ill patients: validation of the confusion assessment method for the Intensive Care Unit (CAM-ICU).
    EW Ely, R Margolin, J Francis et al. Critical Care Medicine 2001; 29: 1370-79
  • Delirium in mechanically ventilated patients. Validity and reliability of the confusion assessment method for the Intensive Care Unit (CAM-ICU).
    EW Ely, SK Inouye, GR Bernard et al. JAMA 2001; 286: 2701-10
  • Monitoring sedation status over time in ICU patients. Reliability and Validity of the Richmond Agitation-Sedation Scale (RASS).
    EW Ely, B Truman, A Shintani. JAMA 2003; 289: 2983-91
  • Intensive Care Delirium Screening Checklist: evaluation of a new screening tool.
    N Bergeron, MJ Dubois, M Dumont et al. Intensive Care Medicine 2001;27: 859-64
  • Is disturbance of consciousness an important feature of ICU delirium?
    N Bergeron, Y Skrobik and MJ Dubois. Intensive Care Medicine 2005; 31: 887
  • Delirium assessment in the critically ill.
    JW Devlin, JJ Fong, GL Fraser and RR Riker. Intensive Care Medicine 2007; 33: 929-40
  • Screening methods for delirium: don’t get confused!
    KH Polderman. Intensive Care Medicine 2007; 33: 3-5
  • Comparison of the confusion assessment method for the Intensive Care Unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) in critical care patients gives high agreement rate(s).
    K Plaschke, R von Haken, M Scholz et al. Intensive Care Medicine 2007; 34: 431-36
  • Comparison of delirium assessment tools in a mixed intensive care unit.
    MM van Eijk, RJ van Marum, IA Klijn et al. Critical Care Medicine 2009; 37 2102-3.
  • Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients.
    JW Devlin, JJ Fong, G Schumaker et al Critical Care Medicine 2007; 35; 2721-2724
  • Routine delirium monitoring in a UK critical care unit.
    VJ Page, S Navarange, S Gama and DF McAuley. Critical Care 2009; 13: R16
  • Recognition of delirium in ICU patients: a diagnostic study of the NEECHAM confusion scale in ICU patients.
    HE Immers, MJ Schuurmans and JJ van de Bijl BMC Nursing 2005; 4: 7
  • A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in non-intubated patients.
    B Van Rompaey, MJ Schuurmans, LM Shortridge-Baggett et al. Critical Care 2008; 12: R16
  • Delirium and sedation in the intensive care unit: survey of behaviours and attitudes of 1384 healthcare professionals.
    RP Patel, M Gambrell, T Speroff et al. Critical Care Medicine 2009; 37: 825-32
  • Comparison of three scores to screen for delirium in the recovery room.
    FM Radtke, M Franck, M Schneider et al. British Journal of Anaesthesia 2008;101;338-43
  • Different assessment tools for intensive care unit delirium: Which score to use?
    A Leutz, A Heymann, FM Radtke et al. Critical Care Medicine 2010; 38: 409-418
  • Understanding barriers to delirium care: a multicentre survey of knowledge and attitudes amongst UK junior doctors.
    D Davis, A MacLullich Age and Ageing 2009; 38: 559-63
  • Implementation of a delirium assessment tool in the ICU can influence haloperidol use.
    M van Den Boogaard, P Pickkers, H van der Hoeven et al. Critical Care 2009; 13: R131.
  • Combined didactic and scenario-based education improves the ability of intensive care unit staff to recognize delirium at the bedside.
    JW Devlin, R Marquis, RR Riker et al. Critical Care 2008; 12: 19.
  • Large-scale implementation of sedation and delirium monitoring in the intensive care unit: A report from two medical centers.
    B Truman, SM Gordon, JF Peterson et al. Critical Care Medicine 2005; 33: 1199-1205
Pathophysiology
  • Update on the Neuropathogenesis of delirium.
    PT Trzepacz. Dementia and Geriatric Cognitive Disorders. 1999; 10: 330-334
  • Psychotogenic drugs and delirium pathogenesis: the central role of the thalamus.
    J-D Gaudreau and P Gagnon. Medical Hypotheses 2005; 64: 471-5
  • The role of neuroimaging in elucidating delirium pathophysiology.
    DC Alsop, MA Fearing, K Johnson et al. Journal of Gerontology: medical sciences 2006; 61: 1287-1293.
  • Cerebral perfusion changes in older delirious patients using 99m Tc HMPAO SPECT
    TG Fong, ST Bogardus, A Daftary et al. Journal of Gerontology: Medical Sciences 2006; 61: 1294-1299
  • Unravelling the pathophysiology of delirium: a focus on the aberrant stress responses.
    AMJ MacLullich, KJ Ferguson, T Miller et al. Journal of Psychosomatic Research 2008; 65: 229-38.
  • Microglia activation in sepsis: a case-control study.
    AW Lemstra, JCM Groen in’t Woud, JJM Hoozemans et al. Journal of Neuroinflammation 2007; 4: 4
  • Brain autopsy findings in intensive care patients previously suffering from dementia: A pilot study.
    DR Janz, TW Abel, JC Jackson et al. Journal of Critical Care 2010; 25: 538e7-538e12
  • Sepsis-associated delirium.
    M Ebersoldt, T Sharshar, D Annane. Intensive Care Medicine 2007; 33: 941-50
  • Is severe sepsis a neuroendocrine disease?
    RS Munford and KJ Tracey. Molecular medicine 2002; 8: 437-42
  • The septic brain.
    EL Streck, CM Comim, T Barichello and J Quevedo. Neurochemistry research 2008; 33: 2171-77
  • The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation
    VA Pavlov, H Wang, CJ Czura. Molecular Medicine 2003; 9: 125-134
  • Sepsis causes neuroinflammation and concominant decrease of cerebral metabolism.
    A Semmler, S Hermann, F Mormann et al. Journal of Neuroinflammation 2008; 5: 38
  • Time-course of cytokines during delirium in elderly patients with hip fractures.
    BC van Munster, JC Korevaar, AH Zwinderman et al. JAGS 2008; 56: 1704-9
  • C-reactive protein levels predict the incidence of delirium and recovery from it.
    A MacDonald, D Adamis, A Treloar, F Martin. Age and Ageing 2007; 36: 222-225
  • Cytokines and acute phase response in delirium.
    SE de Rooij, BC van Munster, JC Korevaar and M Levi. Journal of Psychosomatic Research 2007; 62: 521-25
  • Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium.
    C Murray, DJ Sanderson, C Barkus. Neurobiology of Aging epub May 12 2010
  • Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment.
    JR Maldonado Critical Care Clinics 2008; 24: 789-856
  • Is delirium after cardiac surgery related to plasma amino acids and physical condition?
    RC van der Mast, WW van den Broek, D Fekkes et al. The Journal of Neuropsychiatry and Clinical Neurosciences 2000; 12: 57-63
  • Dispelling myths in the treatment of hepatic encephalopathy.
    D Shawcross and R Jalan. The Lancet 2005; 365: 431-3
  • Participation in activity and risk for incident delirium.
    FM Yang, SK Inouye, MA Fearing et al JAGS 2008; 56: 1479-84
  • The concept of cognitive reserve: a catalyst for research.
    Y Stern. Journal of clinical and experimental neuropsychology 2003; 25: 589-93
  • Pathogenesis of hepatic encephalopathy in acute liver failure.
    J Vaquero, C Chung, ME Cahill and AT Blei. Seminars in liver disease 2003; 23: 259-69
  • Does educational attainment contribute to risk for delirium? A potential role for cognitive reserve.
    RN Jones, FM Yang, Y Zhang et al. Journal of Gerontology medical sciences. 2006; 61: 1307-1311
  • Potential mechanisms and markers of critical illness-associated cognitive dysfunction.
    EB Milbrandt and DC Angus. Current Opinion in Critical Care 2005; 11: 355-9
  • APOE related alterations in cerebral activation even at college age.
    N Scarmeas, CG Habeck, J Hilton et al. Journal of neurology, neurosurgery and psychiatry 2005; 76: 1440-44
  • EEG changes and serum anticholinergic activity measured in patients with delirium in the intensive care unit.
    K Plaschke, H Hill, R Engelhardt et at Anaesthesia 2007; 62: 1217-23
  • Serum anticholinergic activity and cerebral cholinergic dysfunction: An EEG study in frail elderly with and without delirium.
    C Thomas, U Hestermann, J Kopitz et al. BMC Neuroscience 2008; 9: 86
  • Flaws in the serum anticholinergic activity assay: implications for the study of delirium.
    EA Cox, SG Kwatra, S Shetty et al. JAGS 2009; 57: 1707-8
  • Serum S100B in elderly patients with and without delirium
    BC van Munster, JC Korevaar, CM Korse International Journal of Geriatric Psychiatry 2010; 25: 234-9
  • Serum tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients.
    P Pandharipande, A Morandi, JR Adams et al. Intensive Care Medicine 2009; 85: 1886-92
  • Impaired oxidative metabolism precipitates delirium: a study of 101 ICU patients.
    JS Seaman, J Schillerstrom, D Carroll and TM Brown. Psychosomatics 2006; 47: 56-61
  • Cerebrospinal fluid in long-lasting delirium compared with Alzheimer’s dementia.
    GA Caplan, T Kvelde, C Lai et al Journal of Gerontology: medical sciences 2010; 65: 1130-6
Prevention
  • A mulitcomponent intervention to prevent delirium in hospitalized older patients.
    SK Inouye, ST Bogardus, PA Charpentier et al. NEJM 1999; 340: 669-676
  • The role of adherence on the effectiveness of nonpharmacological interventions.
    SK Inouye, ST Bogardus et al. Archives of Internal Medicine. 2003; 163: 958-964
  • The effects of a targeted mulitcomponent delirium intervention on postdischarge outcomes for hospitalized older adults.
    ST Bogardus, MM Desai, CS Willliams et al. American Journal of Medicine 2003; 114: 383-90
  • Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial) a randomised controlled trial.
    T Girard, JP Kress, BD Fuchs et al. Lancet 2008; 371: 126-34
  • A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial.
    T Strom, T Martinussen, P Toft Lancet 2010; 375: 475-80
  • An analgesia-delirium-sedation protocol for critically ill trauma patients reduces ventilator days and hospital length of stay.
    Journal of trauma, injury, infection and critical care. 2008; 65: 517-26
  • Interventions for preventing delirium in hospitalised patients
    N Siddiqui, R Stockdale, AM Britton and J Holmes. Cochrane Database of Systematic Reviews 2007 Issue 2 Art no: CD005563
  • Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial.
    MG Cole, J McCusker, F Bellavance et al. CMAJ 2002; 167: 753-9
  • A multifactorial intervention program reduces the duration of delirium, length of hospitalization and mortality in delirious patients.
    M Lundstrom, A Edlund, S Karlsson et al. JAGS 2005; 53: 622-28
  • Geriatric ward hospitalization reduced incidence delirium among older medical patients
    M Bo, B Martini, C Ruatta et al. American Journal of Geriatric Psychiatry 2009; 17: 760-768
  • Reducing delirium after hip fracture.
    ER Marcantonio, JM Flacker, J Wright and NM Resnick. JAGS 2001; 49: 516-22
  • Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.
    KJ Kalisvaart, JF de Jonghe, MJ Bogaards et al. JAGS 2005; 53: 1658-66
  • Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial.
    WD Schweickert, MC Pohlman, AS Pohlman et al. Lancet 2009; 373: 1874-82
  • Randomized trial of a delirium abatement program for postacute skilled nursing facilities.
    ER Marcantonio, MA Bergman, DK Kiely et al. JAGS 2010; 58: 1109-26
  • Intensive Care Delirium. The effect of outside deprivation in a windowless unit.
    LM Wilson. Archives of Internal Medicine 1972; 130: 225-226
  • An educational intervention can prevent delirium on acute medical wards.
    N Tabet, S Hudson, V Sweeney et al. Age and Ageing 2005; 34: 152-6
Pharmacological management
Haloperidol
  • A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients.
    W Breitbart, R Marotta, M Platt et al. American Journal of Psychiatry 1996; 153: 231-7
  • Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients.
    EB Milbrandt, A Kersten, L Kong et al. Critical Care Medicine 2005; 33: 226-9
  • Olanzapine vs haloperidol: treating delirium in a critical care setting.
    YK Skrobik, N Bergeron, M Dumont and SB Gottfried. Intensive Care Medicine 2004; 30: 444-449
  • Guidelines for the Pharmacological treatment of neurobehavioral sequelae of traumatic brain injury.
    DL Warden, B Gordon, TW McAllister et al Journal of Neurotrauma 2006; 23: 1468-1501
  • Neuroleptic malignant syndrome in traumatic brain injury patients treated with haloperidol.
    C Bellamy, S Kane-Gill, B Falcione, A Seybert The Journal of Trauma, Injury, Infection and Critical Care 2009; 66: 954-958
  • A meta-analysis of cognitive change with haloperidol in clinical trials of atypical antipsychotics: dose effects and comparison to practice effects.
    ND Woodward, SE Purdon, HY Meltzer, DH Zald Schizophrenia Research 2007; 89: 211-224
  • Use of high-dose intravenous haloperidol in the treatment of agitated cardiac patients.
    GE Tesar, GB Murray and NH Cassem. Journal of Clinical Psychopharmacology 1985; 5: 344-47
  • Continuous infusion of haloperidol controls agitation in critically ill patients.
    R Riker, G Fraser, P Cox. Critical Care Medicine 1994; 22: 433-40
  • The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study.
    S Kapur, R Zipursky, P Roy et al. Psychopharmacology 1997; 131: 148-52
  • Relationship between Dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia.
    S Kapur, R Zipursky, G Remington and S Houle. American Journal of Psychiatry 2000; 157: 515-20
  • Haloperidol in palliative care.
    J Vella-Brincat, AD MacLeod. Palliative Medicine 2004; 18: 195-201
  • Haloperidol plasma levels and drug optimization.
    W Coryell, DD Miller, and PJ Perry. American Journal of Psychiatry 1998; 155: 48-53
  • Predicting haloperidol occupancy of central dopamine D2 receptors from plasma levels.
    PB Fitzgerald, S Kapur, G Remington et al. Psychopharmacology 2000; 149: 1-5
  • Interaction of haloperidol plasma level and antipsychotic effect in early phases of acute psychosis treatment.
    I Giegling, A Drago, M Schafer et al. Journal of Psychiatric Research 2010; 44: 487-92
  • Low-dose haloperidol-associated QTc prolongation.
    K Stepkovitch, GH Bahn, R Gupta. JAGS 2008; 56: 1963-85
  • Dopamine and antipsychotic drug action revisited.
    HM Jones and LS Pilowsky. British Journal of Psychiatry2002; 181: 271-75
  • The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment.
    J Brockmoller, J Kircheiner, J Schmider et al. Clinical Pharmacology and Therapeutics 2002; 72: 438-52
  • Intravenous administration of haloperidol to healthy volunteers: lack of subjective effects but clear objective effects.
    JH Williams, NA Wellman, DP Geaney et al. Journal of Psychopharmacology 1997; 11: 247-52
  • Torsades de pointes associated with the administration of intravenous haloperidol: a review of the literature and practical guidelines for use.
    HA Hassaballa and RA Balk. Expert Opinion on Drug Safety 2003; 2: 543-7
  • Old drug, new tricks: haloperidol inhibits secretion of proinflammatory cytokines.
    RJ Moots, Z Al-Saffar, D Hutchinson et al. Annals of Rheumatic Diseases 1999; 58: 585-7
  • Differential effects of single versus multiple administrations of haloperidol and risperidone on functional outcome after experimental brain trauma.
    AE Kline, JL Massucci, RD Zafonte. Critical Care Medicine 2007; 35: 919-24
  • Administration of haloperidol and risperidone after neurobehavioral testing hinders the recovery of traumatic brain injury-induced deficits.
    AN Hoffman, JP Cheng, RD Zafonte, AC Kline. Life Sciences 2008; 83: 602-7
Antipsychotics – general
  • Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients.
    H Lacasse, MM Perreault and DR Williamson. Annals of Pharmacotherapy 2006; 40: 1966-73
  • Management of alcohol withdrawal delirium. An evidence-based practice guideline.
    MF Mayo-Smith, LH Beecher, TL Fischer et al. Archives of Internal Medicine 2004; 164: 1405-12
  • Atypical antipsychotics: mechanism of action.
    P Seeman. Focus 2004; 2: 48-58
  • Dopamine and antipsychotic drug action revisited.
    HM Jones and LS Pilowsky British Journal of Psychiatry 2002; 181: 271-5
  • A meta-analysis and critical review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: opening a closed book.
    AL Mishara and TE Goldberg. Biological Psychiatry 2004; 55: 1013-22
  • Administration of olanzapine to prevent postoperative delirium in elderly joint-replacement patients: a randomized controlled trial.
    LA Larsen, SE Kelly, TA Stern et al. Psychosomatics 2010; 51: 409-18
  • Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery – a randomized controlled trial.
    M Gamberini, D Bolliger, GA Lurati Buse et al. Critical Care medicine 2009 37: 1762-68
  • Efficacy of risperidone in treating the hyperactive symptoms of delirium.
    C-Y Lui, Y-Y Juang, H-Y Liang et al International Clinical Psychopharmacology 2004; 19: 165-68
  • Efficacy and safety of quetiapine in critically ill patients with delirium: A prospective, multicenter, randomized, double-blind placebo-controlled pilot study.
    JW Devlin, RJ Roberts, JJ Fong et al. Critical Care Medicine 2010; 38: 419-27
  • A randomised controlled trial of quetiapine versus placebo in the treatment of delirium.
    TA Tahir, E Eeles, V Karapareddy et al Journal of Psychosomatic Research 2010; 69: 485-90
  • Feasibility, efficacy and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial.
    T Girard, P Pandharipande, S Carson et al. Critical Care Medicine 2010; 38: 428-37
  • Risperidone versus olanzapine for the treatment of delirium.
    S-W Kim, J-A Yoo, S-Y Lee et al. Human Psychopharmacology 2010; 25: 298-302
  • Ondansetron hydrochloride for the treatment of delirium after coronary artery surgery.
    O Bayindir, M Guden, B Akpinar et al. Journal of Thoracic and Cardiovascular Surgery 2001; 121: 176-7
  • Adjunctive valproic acid for delirium and/or agitation on a consultation-liaison service: a report of six cases.
    JA Bourgeois, AK Koike, JE Simmons et al. Journal of Neuropsychiatry and Clinical Neurosciences 2005; 17: 232-38
Side effects antipsychotics
  • Neither atypical nor conventional antipsychotics increase mortality or hospital admissions among elderly patients with dementia: a two year prospective study.
    M Raivio, JV Laurila, TE Strandberg et al. American Journal of Geriatric Psychiatry 2007; 15: 416-24
  • Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications.
    HC Kales, M Valenstein, H Myra Kim et al. American Journal of Psychiatry 2007; 164: 1568-76
  • Antipsychotic therapy and short-term serious events in older adults with dementia.
    PA Rochon, S-L Normand, T Gomes et al. Archives of Internal Medicine 2008; 168: 1090-1096
  • Association of antipsychotic use with hospital events and mortality among medicare beneficiaries residing in long-term care facilities.
    L Simoni-Wastila, PT Ryder, J Qian et al. American Journal of Geriatric Psychiatry 2009; 17: 417-27
  • Comparing acute toxicity of first and second generation antipsychotic drugs: a 10 year retrospective cohort study.
    MA Ciranni, TE Kearney and KR Olson. Journal of Clinical Psychiatry 2009; 70: 122-9
  • Atypical antipsychotic drugs and the risk of sudden cardiac death.
    WA Ray, CP Chung, KT Murray et al. NEJM 20009; 360: 225-35
  • Risk of death in elderly users of conventional vs. atypical antipsychotic medications.
    PS Wang, PH Sebastian Schneeweiss, J Avorn et al. NEJM 2005; 353: 2335-41
  • Risk of death with atypical antipsychotic drug treatment for dementia. Meta-analysis of randomized controlled trials.
    LS Schneider, KS Dagerman and P Insel. JAMA 2005; 294: 1934-43
  • Potential causes of higher mortality in elderly users of conventional and atypical antipsychotic medications.
    S Setoguchi, PS Wang, M A Brookhart et al. JAGS 2008; 56: 1644-50
  • Antipsychotic drug use and risk of pneumonia in elderly people.
    W Know, RJ van Marum, PA Jansen et al. JAGS 2008; 56: 661-6
  • Drugs with anticholinergic properties: cognitive and neuropsychiatric side-effects in elderly patients.
    I Cancelli, M Beltrame, GL Gigli, M Valente. Neurological Sciences 2009; 30: 87-92
Guidelines
  • Clinical Practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.
    JJ Jacobi, GL Fraser, DB Coursin et al Critical Care Medicine 2002; 30: 119-41
  • A survey of delirium guidelines in Europe.
    A Leentjens and A Diefenbacher. Journal of Psychosomatic Research 2006; 61: 123-8
  • The prevention, diagnosis and management of delirium in older people: concise guidelines
    J Potter and J George. Clinical Medicine 2006; 6: 303-8
  • Do guidelines improve the process and outcomes of care in delirium?
    LY Young and J George. Age and Ageing 2003; 32: 525-8
  • Reducing Iatrogenic Risks: ICU-acquired delirium and weakness – crossing the quality chasm.
    EE Vasilevskis, EW Ely, T Speroff et al. Chest 2010; 138: 1224-33
Palliative Care
  • Neuroleptic dose in the management of delirium in patients with advanced cancer.
    D Hui, S Bush, L Gallo et al Journal of Pain and Symptom Management 2010; 39: 186-96
  • Symptom distress, interventions and outcomes of intensive care unit cancer patients referred to a palliative care consult team.
    ML Delgado-Guay, HA Parsons, Z Li et al. Cancer 2009; 115: 437-45
  • Symptoms of depression and delirium assessed serially in palliative-care inpatients.
    M Leonard, J Spiller, J Keen et al. Psychosomatics 2009; 50: 506-14
  • The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers and their nurses.
    W Breitbart, C Gibson and A Tremblay. Psychosomatics 2002; 43: 183-94
  • Anticipation of distress after discontinuation of mechanical ventilation in the ICU at the end of life.
    EJ Kompanje, B van der Hoven and J Bakkker. Intensive Care Medicine 2008; 34: 1593-1599
  • Impact of delirium and recall on the level of distress in patients with advanced cancer and their family caregivers.
    E Bruera, SH Bush, J Willey et al. Cancer 2009; 115: 2004-12
  • Reversibility of delirium in terminally ill patients and predictors of mortality.
    M Leonard, B RAju, M Conroy et al. Palliative Medicine 2008; 22: 848-854
  • Occurrence, causes and outcome of delirium in patients with advanced cancer.
    PG Lawlor, G Gagnon, IL Mancini et al. Archives of Internal Medicine 2000; 160: 786-94
  • Differing management of people with advanced cancer and delirium by four sub-specialities.
    M Agar, DC Currow, J Plummer et al. Palliative Medicine 2008; 22: 633-40
  • Delirium as a contributing factor to “crescendo” pain: three case reports.
    N Coyle, W Breitbart, S Weaver and R Portenoy. Journal of Pain and Symptom management 1994; 9: 44-47
Legal Aspects
  • Informed consent in the critically ill: a two step approach incorporating delirium screening
    E Fan, S Shahid, P Kondreddi et al. Critical Care Medicine 2008; 36: 94-99
  • Safeguarding the rights of patients who lack capacity in general hospitals. Do the Bournewood proposals for England and Wales help or hinder?
    RH Harwood, R Stewart, Peter Barlett. Age and Ageing 2007; 36: 120-1
  • British Association of Critical Care Nurses position statement on the use of restraint in adult critical care units.
    K Bray, K Hill, W Robson et al. Nursing in Critical Care 2004; 9: 199-211
ICU Delirium in Practice
  • Reducing iatrogenic risks: ICU-acquired delirium and weakness – crossing the quality chasm.
    EE Vasilevskis, EW Ely, T Speroff et al. Chest 2010; 138: 1224-33
  • Creating the animated intensive care unit.
    JB Hall. Critical Care Medicine 2010; 38: S668-75
  • A screening, prevention, and restoration model for saving the injured brain in intensive care unit survivors.
    EE Vasilevskis, PP Pandharipande, TD Girard and EW Ely. Critical Care Medicine 2010; 38: S683-S91