Delirium in the Intensive Care Unit: An Under-Recognized Syndrome of Organ Dysfunction

ABSTRACT

The intensivist should think of delirium, or acute central nervous system dysfunction, as the brain's form of ``organ dysfunction.'' Delirium is extremely common in intensive care unit (ICU) patients due to factors such as comorbidity, critical illness, and iatrogenesis. This complication of hospital stay is extremely hazardous in older persons and is associated with prolonged hospital stays, institutionalization, and death. Neurologic dysfunction compromises patients' ability to be removed from mechanical ventilation or achieve full recovery and independence. Yet ICU nurses and physicians are usually unaware of the presence of hypoactive delirium and only recognize this disturbance in agitated patients (hyperactive delirium). More importantly, there are few studies that have included ICU patients in the assessment or prevention of delirium. This article reviews the definition and salient features of delirium, its primary risk factors, a newly validated instrument for delirium assessment that is being developed for ICU nurses and physicians, and pharmacological agents associated with the development of delirium and used in its management.

KEYWORD

Delirium - aging - geriatrics - cognitive impairment - mechanical ventilation - sedatives - analgesics - respiratory diseases - critical care

REFERENCES

• 1 Papadopoulos M C, Davies D C, Moss R F, Tighe D, Bennett E D. Pathophysiology of septic encephalopathy: a review.  Crit Care Med . 2000;  28 3019-3024
• 2 Russell J A, Singer J, Bernard G, Wheeler A, Fulkerson W J, Hudson L D. Changing pattern of organ dysfunction in early human sepsis is related to mortality.  Crit Care Med . 2000;  28 3405-3411
• 3 Legault S E, Joffe R T, Armstrong P W. Psychiatric morbidity during the early phase of coronary care for myocardial infarction: association with cardiac diagnosis and outcome.  Can J Psychiatry . 1992;  37 316-325
• 4 Inouye S K, Rushing J T, Foreman M D, Palmer R M, Pompei P. Does delirium contribute to poor hospital outcomes?.  <~>A three-site epidemiologic study. J Gen Intern Med . 1998;  13 234-242
• 5 O'Keeffe S, Lavan J. The prognostic significance of delirium in older hospital patients.  J Am Geriatr Soc . 1997;  45 174-178
• 6 Hebert P C, Drummond A J, Singer J, Bernard G R, Russell J A. A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome.  Chest . 1993;  104 230-235
• 7 Francis J, Martin D, Kapoor W N. A prospective study of delirium in hospitalized elderly.  JAMA . 1990;  263(8) 1097-1101
• 8 Inouye S K, Schlesinger M J, Lyndon T J. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care.  Am J Med . 1999;  106 565-573
• 9 Ely E W, Baker A M, Dunagan D P, Burke H L, Smith A C, Kelly P T. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously.  N Engl J Med . 1996;  335(25) 1864-1869
• 10 Ely E W, Namen A M, Tatter S, Lucia M A, Smith A C, Landry S. Impact of a ventilator weaning protocol in neurosurgical patients: a randomized, controlled trial.  Am J Respir Crit Care Med . 1999;  159 A370
• 11 Namen A M, Ely E W, Case D, Lucia M A, Tatter S, Smith A C. Predictors of successful extubation in neurosurgical patients.  Am J Respir Crit Care Med . 2001;  163 658-664
• 12 Vallverdu I, Calaf N, Subirana M, Net A, Benito S, Mancebo J. Clinical characteristics, respiratory functional parameters, and outcome of a two-hour T-piece trial of patients weaning from mechanical ventilation.  Am J Respir Crit Care Med . 1999;  158 1855-1862
• 13 Granberg A, Engberg B, Lundberg D. Intensive care syndrome.  Intensive and Critical Care Nurse . 1996;  12 173-182
• 14 Wilson L M. Intensive care delirium: the effect of outside deprivation in a windowless unit.  Arch Intern Med . 1972;  130 22-23
• 15 Geary S M. Intensive care unit psychosis revisited: understanding and managing delirium in the critical care setting.  Crit Care Nurse . 1994;  17 51-63
• 16 Meagher D J, Hanlon D O, Mahony E O, Casey P R, Trzepacz P T. Relationship between symptoms and motoric subtype of delirium.  J Neuropsychiatry Clin Neurosci . 2000;  12 51-56
• 17 McGuire B E, Basten C J, Ryan C J, Gallagher J. Intensive care unit syndrome: a dangerous misnomer.  Arch Intern Med . 2000;  160 906-909
• 18 Justic M. Does ``ICU psychosis'' really exist?.  Critical Care Nurse . 2000;  20 28-37
• 19 National Research Council. The Aging Mind: Opportunities in Cognitive Research. Stern PC, Carstensen LL, eds. Washington, DC: National Academy Press; 2000: 1-249
• 20 Levkoff S E, Evans D A, Liptzin B, Clearly P D, Lipsitz L A, Wetle T T. Delirum: the occurrence and persistence of symptoms among elderly hospitalized patients.  Arch Intern Med . 1992;  152 334-340
• 21 Heffner J E. A wake-up call in the intensive care unit.  N Engl J Med . 2000;  342 1520-1522
• 22 Epstein S K, Ciubotaru R L, Wong J B. Effect of failed extubation on the outcome of mechanical ventilation.  Chest . 1997;  112(1) 186-192
• 23 Epstein S K, Ciubotaru R L. Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation.  Am J Respir Crit Care Med . 1998;  158 489-493
• 24 Torres A, Gatell J M, Aznar E. Reintubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation.  Am J Respir Crit Care Med . 1995;  152 137-141
• 25 Esteban A, Alia I, Gordo F, Fernandez R, Solsona J F, Vallverdu I. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation.  Am J Respir Crit Care Med . 1997;  156 459-465
• 26 Kollef M H, Levy N T, Ahrens T, Schaiff R, Prentice D, Sherman G. The use of continuous IV sedation is associated with prolongation of mechanical ventilation.  Chest . 1999;  114 541-548
• 27 Francis J. Delirium in older patients.  J Am Geriatr Soc . 1992;  (40) 829-838
• 28 Francis J, Kapoor W N. Delirium in hospitalized elderly.  J Gen Intern Med . 1990;  (5) 65-79
• 29 Inouye S K. The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluation of delirium in hospitalized elderly medical patients.  Am J Med . 1994;  97 278-288
• 30 Armstrong-Esther C A, Browne K D. The influence of elderly patients' mental impairment on nurse-patient interaction.  J Adv Nurs . 1986;  11(4) 379-387
• 31 Wray N P, Friedland J A, Ashton C M, Scheurich J, Zollo A J. Characteristics of house staff work rounds on two academic general medicine services.  J Med Educ . 1986;  61 893-900
• 32 Inouye S K, Bogardus S T, Charpentier P A, Leo-Summers L, Acampora D, Holford T R. A multicomponent intervention to prevent delirium in hospitalized older patients.  N Engl J Med . 1999;  340 669-676
• 33 Williams-Russo P, Urquhart B L, Sharrock N E, Charlson M E. Post-operative delirium: predictors and prognosis in elderly orthopedic patients.  J Am Geriatr Soc . 1992;  40 759-767
• 34 >Statistical Abstract of the United States. Washington, DC: Bureau of the Census 1996
• 35 Ely E W, Baker A M, Evans G W, Haponik E F. The cost of respiratory care in mechanically ventilated patients with chronic obstructive pulmonary disease.  Crit Care Med . 2000;  28 408-413
• 36 Hopkins R O, Weaver L K, Pope D, Orme J F, Bigler E D, Larson-Lohr V. Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome.  Am J Respir Crit Care Med . 1999;  160 50-56
• 37 Sloss E M, Solomon D H, Shekelle P G, Young R T, Saliba D, MacLean C H. Selecting target conditions for quality of care improvement in vulnerable older adults.  J Am Geriatr Soc . 2000;  48 363-369
• 38 Ely E W, Evans G W, Haponik E F. Mechanical ventilation in a cohort of elderly patients admitted to an intensive care unit.  Ann Intern Med . 1999;  131 96-104
• 39 Marcantonio E R, Goldman L, Mangione C M, Ludwig L E, Muraca B, Haslauer C M. A clinical prediction rule for delirium after elective noncardiac surgery.  JAMA . 1994;  271 134-139
• 40 Marcantonio E R, Juarez G, Goldman L, Mangione C M, Ludwig L E, Lind L. The relationship of postoperative delirium with psychoactive medications.  JAMA . 1994;  272 1518-1522
• 41 Inouye S K, van Dyck H C, Alessi C A, Balkin S, Siegal A P, Horowitz R I. Clarifying confusion: the confusion assessment method.  Ann Intern Med . 1990;  113 941-948
• 42 Hobbs F, Damon B L, Taeuber C M. Sixty-Five Plus in the United States. Washington, DC: U.S. Department of Commerce, Economics, and Statistics Administration, Bureau of the Census; 1996
• 43 Sage W M, Hurst C R, Silverman J F, Bortz W M. Intensive care for the elderly: outcome of elective and nonelective admissions.  J Am Geriatr Soc . 1987;  35 312-318
• 44 Baltussen R, Leidl R, Ament A. The impact of age on cost-effectiveness ratios and its control in decision making.  Health Economics . 1996;  5(3) 227-239
• 45 Shaw A B. Age as a basis for healthcare rationing: support for agist policies.  Drugs & Aging . 1996;  9(6) 403-405
• 46 Angus D C, Kelly M A, Schmitz R J, White A, Popovich J, for the Committee on Manpower for Pulmonary and Critical Care Societies (COMPACCS). Current and projected workforce requirements for care of the critically ill and patients with pulmonary disease: can we meet the requirements of an aging population?.  JAMA . 2000;  284 2762-2770
• 47 Behrendt C E. Acute respiratory failure in the United States: incidence and 31-day survival.  Chest . 2000;  118 1100-1105
• 48 Jakob S M, Rothen H U. Intensive care 1980-1995; change in patient characteristics, nursing workload and outcome.  Intensive Care Medicine . 1997;  23 1165-1170
• 49 Chelluri L, Grenvik A, Silverstein M. Intensive care for critically ill elderly: mortality, costs, and quality of life: review of the literature.  Arch Intern Med . 1995;  155 1013-1022
• 50 Ely E W, Margolin R, Francis J, May L, Truman B, Wheeler A P, Bernard G B, Inouye S K. Delirium in the ICU: measurement and outcomes.  Am J Respir Crit Care Med . 2001 (in press); 
• 51 Hamel M B, Philips R S, Teno J M, Lynn J, Galanos A N, Davis R B. Seriously ill hospitalized adults: do we spend less on older patients?.  J Am Geriatr Soc . 1996;  44 1043-1048
• 52 Hamel M B, Teno J M, Goldman L, Lynn J, Davis R B, Galanos A N. Patient age and decisions to withhold life-sustaining treatments from seriously ill, hospitalized adults.  Annals of Internal Medicine . 1999;  130 116-125
• 53 American Psychiatric Association. Practice guidelines for the treatment of patients with delirium.  Am J Psychiatry . 1999;  156(5 suppl) 1-20
• 54 Francis J, Kapoor W N. Prognosis after hospital discharge of older medical patients with delirium.  J Am Geriatr Soc . 1992;  (40) 601-606
• 55 Blessed G, Tomlinson B E, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects.  Brit J Psychiat . 1968;  114 797-811
• 56 Inouye S K, Charpentier P A. Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability.  JAMA . 1996;  275 852-857
• 57 Inouye S K, Viscoli C, Horwitz R I, Hurst L D, Tinetti M E. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics.  Ann Intern Med . 1993;  (119) 474-481
• 58 Lynch E P, Lazor M A, Gellis J E, Orav J, Goldman L, Marcantonio E R. The impact of postoperative pain on the development of postoperative delirium.  Anesth Anal . 1998;  86 781-785
• 59 Fish D N. Treatment of delirium in the critically ill patient.  Clin Pharm . 1991;  10 456-466
• 60 Francis J. Drug-induced delirium.  CNS Drugs . 1996;  5 103-114
• 61 Zhou H H, Sheller J R, Nu H, Wood M, Wood A JJ. Ethnic differences in response to morphine.  Clin Pharmacol Ther . 1993;  54 507-513
• 62 Salzman C. Clinical Geriatric Psychopharmacology, 3rd ed. Baltimore: Williams & Wilkins 1998: 58-545
• 63 Tateishi T, Wood A JJ, Guengerich F P, Wood M. Biotransformation of tritiated fentanyl in human liver microsomes.  Biochemical Pharmacology . 1995;  50 1921-1924
• 64 Yun C, Wood M, Wood A JJ, Guengerich F P. Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4:an explanation of the variable elimination clearance.  Anesthesiology . 1992;  77 467-474
• 65 Wood A JJ. Drug metabolism. In: Wood M, Wood AJJ, eds. Drugs and Anesthesia: Pharmacology for Anesthetists Baltimore: Williams & Wilkins; 1990
• 66 Wood A JJ. Drug disposition and pharmacokinetics. In: Wood M, Wood AJJ, eds. Drugs and Anesthesia: Pharmacology for Anesthetists Baltimore: Williams & Wilkins; 1990
• 67 Macnab M SP, Macrae D J, Guy E. Profound reduction in morphine clearance and liver blood flow in shock.  Intensive Care Med . 1986;  12 366-369
• 68 Alazia M, Levron J C, Guidon C. Pharmacokinetics of fentanyl during continuous infusion in critically ill patients.  Anaesthesia . 1987;  67 A665-A666
• 69 Hassan E, Fontaine D K, Nearman H S. Therapeutic considerations in the management of agitated and delirious critically ill patients.  Pharmacotherapy . 1998;  18 113-129
• 70 Brook A D, Ahrens T S, Schaiff R, Prentice D, Sherman G, Shannon W. Effect of a nursing implemented sedation protocol on the duration of mechanical ventilation.  Crit Care Med . 1999;  27 2609-2615
• 71 Kress J P, Pohlman A S, O'Connor M F, Hall J B. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation.  N Engl J Med . 2000;  342 1471-1477
• 72 Strub R L, Black F W. The Mental Status Examination in Neurology.  3rd ed. Philadelphia: FA Davis 1993: 1-210
• 73 Plum F, Posner J. The Diagnosis of Stupor and Coma.  3rd ed. Philadelphia: FA Davis; 1980
• 74 Teasdale G, Jennett B. Assessment of coma and impaired consciousness: a practical scale.  Lancet . 1974;  1 81-84
• 75 Ramsay M, Savege T M, Simpson E R. Controlled sedation with aphaxalone-alphadolone.  BMJ . 1974;  2 656-659
• 76 Hansen-Flaschen J, Cowen J, Poloman R C. Beyond the Ramsay scale: need for a validated measure of sedating drug efficacy in the intensive care unit.  Crit Care Med . 1994;  22 732-733
• 77 Devlin J W, Boleski G, Mlynarek M, Nerenz D, Peterson E, Jankowski M. Motor activity assessment scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit.  Crit Care Med . 1999;  27(7) 1271
• 78 Riker R, Picard J T, Fraser G. Prospective evaluation of the sedation-agitation scale for adult critically ill patients.  Crit Care Med . 1999;  27(7) 1325-1329
• 79 Sessler C, Gosnell M, Grap M J, Brophy G T, O'Neal P V, Tesoro E. A new agitation-sedation scale (MASS) for critically ill patients: development and testing of validity and interrater reliability.  Am J Respir Crit Care Med . 2000;  161 A506
• 80 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th ed. Washington, DC: American Psychiatric Association 1994: 123-133
• 81 Trzepacz P T, Baker R W, Greenhouse J. A symptom rating scale for delirium.  Psychiatry Research . 1987;  23 89-97
• 82 Smith M J, Breitbart W S, Meredith M P. A critique of instruments and methods to detect, diagnose, and rate delirium.  J Pain Symptom Management . 1995;  10 35-77
• 83 Hart R P, Levenson J L, Sessler C N, Best A M, Schwartz S M, Rutherford L E. Validation of a cognitive test for delirium in medical ICU patients.  Psychosomatics . 1996;  37 533-546
• 84 Hart R P, Best A M, Sessler C N, Levenson J L. Abbreviated cognitive test for delirium.  J Psychosom Res . 1997;  43 417-423
• 85 Folstein M F, Folstein S E, McHugh P R. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician.  J Psychiat Res . 1975;  12 189-198
• 86 Gelling L. Causes of ICU psychosis: the environmental factors.  Nurs Crit Care . 1999;  4(1) 22-26
• 87 Hansell H N. The behavioral effects of noise on man: the patient with ``intensive care unit psychosis''.  Heart Lung . 1984;  13(1) 59-65
• 88 Dyson M. Intensive care unit psychosis, the therapeutic nurse-patient relationship and the influence of the intensive care setting: analyses of interrelating factors.  Journal of Clinical Nursing . 1999;  8 284-290
• 89 Kahn D, Cook T, Carlisle C, Nelson D, Kramer N, Millman R. Identification and modification of environmental noise in an ICU setting.  Chest . 1998;  114 535-540
• 90 Topf M R, Bookman M R, Arand D P. Effects of critical care unit noise on the subjective quality of sleep.  Journal of Advanced Nursing . 1996;  24 545-551
• 91 Fraser G, Prato B S, Riker R, Berthiaume D, Wilkins M L. Frequency, severity, and treatment of agitation in young versus elderly patients in the ICU.  Pharmacotherapy . 2000;  20 75-82
• 92 Shapiro B A, Warren J, Egol A, Greenbaum D, Jacobi J, Nasraway S. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary.  Critical Care Medicine . 1995;  23 1596-1600
• 93 Wheeler A P. Sedation, analgesia, and paralysis in the intensive care unit.  Chest . 1993;  104 566-577
• 94 Riker R, Fraser G, Cox P. Continuous infusion of haloperidol controls agitation in critically ill patients.  Crit Care Med . 1994;  22 433-440
• 95 Sharma N D, Rosman H, Padhi I D, Tisdale J E. Torsades de Pointes associated with intravenous haloperidol in critically ill patients.  Am J Cardiol . 1998;  81 238-240
• 96 Ely E W, Bennett P A, Bowton D L, Murphy S M, Haponik E F. Large-scale implementation of a respiratory therapist-driven protocol for ventilator weaning.  Am J Respir Crit Care Med . 1999;  159 439-446