Pharmacological and Nonpharmacological Management of Delirium in Critically Ill Patients

Neurotherapeutics

Volumn 9, Issue 1, 2012, Pages 158-175

  Hipp, Dustin M ^a   Ely, E Wesley ^a,b,c  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY   (United States)

^c Associate Director of Aging Research for Tennessee Valley VA GRECC   (United States)

Author keywords

Aging; Anti psychotics; Critical care; Delirium; Dexmedetomidine; Mechanical ventilation

Indexed keywords

ALPHA 1 ADRENERGIC RECEPTOR STIMULATING AGENT; ALPHA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; AMISULPRIDE; ANALGESIC AGENT; ATYPICAL ANTIPSYCHOTIC AGENT; BIOLOGICAL MARKER; CARBAMAZEPINE; CLONIDINE; DEXMEDETOMIDINE; HALOPERIDOL; HYPNOTIC AGENT; LORAZEPAM; MIDAZOLAM; MORPHINE; NEUROLEPTIC AGENT; OLANZAPINE; PHENOBARBITAL; PROPOFOL; QUETIAPINE; QUINIDINE; RIFAMPICIN; RISPERIDONE; RIVASTIGMINE; SEDATIVE AGENT; ZIPRASIDONE;

ADD ON THERAPY; AGITATION; AKATHISIA; AROUSAL; ARTIFICIAL VENTILATION; BRADYCARDIA; BREATHING; CLINICAL ASSESSMENT; CLINICAL PROTOCOL; CONTINUOUS INFUSION; CRITICALLY ILL PATIENT; DELIRIUM; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; EVIDENCE BASED PRACTICE; EXTRAPYRAMIDAL SYMPTOM; HEALTH CARE COST; HEALTH CARE SYSTEM; HEART ARRHYTHMIA; HEART DEATH; HOSPITALIZATION; HUMAN; HYPERTENSION; HYPOTENSION; INCIDENCE; INTENSIVE CARE UNIT; LOW DRUG DOSE; MEDICAL INSTRUMENTATION; NEUROIMAGING; NEUROLEPTIC MALIGNANT SYNDROME; PATHOPHYSIOLOGY; PATIENT CARE; PATIENT MONITORING; PRIORITY JOURNAL; RECEPTOR BLOCKING; REVIEW; RISK FACTOR; SIDE EFFECT; SUDDEN DEATH; TARDIVE DYSKINESIA; TORSADE DES POINTES; VENOUS THROMBOEMBOLISM;

ANALGESICS, NON-NARCOTIC; ANTIPSYCHOTIC AGENTS; CRITICAL CARE; CRITICAL ILLNESS; DELIRIUM; DEXMEDETOMIDINE; HUMANS; RESPIRATION, ARTIFICIAL;

EID: 84856579294     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-011-0102-9     Document Type: Review

References (158)

1. Verghese A. Cutting for Stone. First Vintage Books Edition. Vintage Books, New York, 2009.
2. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004; 291: 1753-1762.
3. Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009; 180: 1092-1097.
4. Lin SM, Liu CY, Wang CH, et al. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med 2004; 32: 2254-2259.
5. Ely EW, Gautam S, Margolin R, et al. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med 2001; 27: 1892-1900.
6. Milbrandt EB, Deppen S, Harrison PL, et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004; 32: 955-962.
7. Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev 2004; 14: 87-98.
8. Iwashyna TJ, Ely EW, Smith DS, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010; 304: 1787-1794.
9. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010; 38: 1513-1520.
10. van den Boogaard M, Schoonhoven L, Evers AW, van der Hoeven JG, van Achterberg T, Pickkers P. Delirium in critically ill patients: Impact on long-term health related quality of life and cognitive functioning. Crit Care Med 2012; 40(1): 112-8.
11. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001; 286: 2703-2710.
12. Guenther U, Popp J, Koecher L, et al. Validity and reliability of the CAM-ICU Flowsheet to diagnose delirium in surgical ICU patients. J Crit Care 2010; 25: 144-151.
13. Spronk PE, Riekerk B, Hofhuis J, Rommes JH. Occurrence of delirium is severely underestimated in the ICU during daily care. Intensive Care Med 2009; 35: 1276-1280.
14. Vasilevskis EE, Ely EW, Speroff T, Pun B, Boehme L, Dittus R. Reducing Iatrogenic risks. ICU-acquired delirium and weakness - crossing the quality chasm. Chest 2010; 138: 1224-1233.
15. Vasilevskis EE, Pandharipande PP, Girard TD, Ely EW. A screening, prevention, and restoration model for saving the injured brain in intensive care unit survivors. Crit Care Med 2010; 38: S683-S691.
16. Landro L. Changing intensive care to improve life afterwards. The Wall Street Journal, Feb. 15, 2011. Available at: http://online. wsj. com/article/SB10001424052748704081604576144321242020948. html. Accessed 7 November, 2011.
17. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edit. Washington, D. C.: American Psychiatric Association, 2000.
18. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007; 298: 2644-2653.
19. Pun B, Ely EW. The importance of diagnosing and managing ICU delirium. Chest 2007; 132: 624-636.
20. 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; 9: R375-R381.
21. Pisani MA, Murphy TE, Araujo KL, Slattum P, van Ness PH, Inouye SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med 2009; 37: 177-183.
22. Morandi A, Pandharipande P, Trabucchi M, et al. Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients. Intensive Care Med 2008; 34: 1907-1915.
23. Pandharipande P, Cotton BA, Shintani A, et al. Motoric subtypes of delirium in mechanically ventilated surgical and trauma intensive care unit patients. Intensive Care Med 2007; 33: 1726-1731.
24. Peterson JF, Pun BT, Dittus RS, et al. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc 2006; 54: 479-484.
25. Pandharipande P, Cotton BA, Shintani A, et al. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma 2008; 65: 34-41.
26. van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for intensive care delirium: a systematic review. Intensive Crit Care Nurs 2008; 24: 98-107.
27. Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001; 27: 1297-1304.
28. Pisani MA, Murphy TE, van Ness PH, Araujo KL, Inouye SK. Characteristics associated with delirium in older patients in a medical intensive care unit. Arch Intern Med 2007; 167: 1629-1634.
29. Yildizeli B, Ozyurtkan MO, Batirel HF, Kuscu K, Bekiroglu N, Yuksel M. Factors associated with postoperative delirium after thoracic surgery. Ann Thorac Surg 2005; 79: 1004-1009.
30. Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care 2008; 12(Suppl 3): S3.
31. Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006; 104: 21-26.
32. Ely EW, Girard TD, Shintani AK, et al. Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients. Crit Care Med 2007; 35: 112-117.
33. van Munster BC, Korevaar JC, Zwinderman AH, Leeflang MM, de Rooij SE. The association between delirium and the apolipoprotein E epsilon 4 allele: new study results and a meta-analysis. Am J Geriatr Psychiatry 2009; 17: 856-862.
34. van Munster BC, Korevaar JC, de Rooij SE, Levi M, Zwinderman AH. The association between delirium and the apolipoprotein E epsilon4 allele in the elderly. Psychiatr Genet 2007; 17: 261-266.
35. Ouimet S, Riker R, Bergeon N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med 2007; 33: 1007-1013.
36. Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30: 119-141.
37. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive care delirium screening checklist: evaluation of a new screening tool. Intensive Care Med 2001; 27: 859-864.
38. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001; 29: 1370-1379.
39. Guenther U, Popp J, Koecher L, et al. Validity and Reliability of the CAM-ICU Flowsheet to diagnose delirium in surgical ICU patients. J Crit Care 2009; 25: 144-151.
40. Tobar E, Romero C, Galleguillos T, et al. [Confusion assessment method for diagnosing delirium in ICU patients (CAM-ICU): cultural adaptation and validation of the Spanish version]. Med Intensiva 2010; 43: 14-21.
41. Luetz A, Heymann A, Radtke F, et al. Different assessment tools for intensive care unit delirium: which score to use? Crit Care Med 2010; 38: 409-418.
42. van Eijk MM, van den Boogaard M, van Marum RJ, et al. Routine use of the confusion assessment method for the intensive care unit: a multicenter study. Am J Respir Crit Care Med 2011; 184: 340-344.
43. Neufeld KJ, Hayat MJ, Coughlin JM, et al. Evaluation of two intensive care delirium screening tools for non-critically ill hospitalized patients. Psychosomatics 2011; 52: 133-140.
44. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990; 113: 941-948.
45. Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of Delirium Rating Scale Revised-98: comparison to the delirium rating scale and cognitive test for delirium. J of Neuropsychiatry and Clin Neurosciences 2001; 13: 229-242.
46. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999; 27: 1325-1329.
47. Riker RR, Fraser GL, Simmons LE, Wilkins ML. Validating the sedation-agitation scale with the bispectral index and visual analog scale in adult ICU patients after cardiac surgery. Intensive Care Med 2001; 27: 853-858.
48. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 2003; 289: 2983-2991.
49. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166: 1338-1344.
50. van den BM, Pickkers P, van der HH, Roodbol G, van AT, Schoonhoven L. Implementation of a delirium assessment tool in the ICU can influence haloperidol use. Crit Care 2009; 13: R131.
51. Pun BT, Gordon SM, Peterson JF, et al. Large-scale implementation of sedation and delirium monitoring in the intensive care unit: a report from two medical centers. Crit Care Med 2005; 33: 1199-1205.
52. Soja SL, Pandharipande PP, Fleming SB, et al. Implementation, reliability testing, and compliance monitoring of the Confusion Assessment Method for the Intensive Care Unit in trauma patients. Intensive Care Med 2008; 34: 1263-1268.
53. Smith HA, Boyd J, Fuchs DC, et al. Diagnosing delirium in critically ill children: Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU). Crit Care Med 2011; 39: 150-157.
54. Girard TD, Kress JP, Fuchs BD, et al. 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. Lancet 2008; 371: 126-134.
55. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009; 301: 489-499.
56. Flaherty JH, Rudolph J, Shay K, et al. Delirium is a serious and under-recognized problem: why assessment of mental status should be the sixth vital sign. J Am Med Dir Assoc 2007; 8: 273-275.
57. Gunther ML, Morandi A, Ely EW. Pathophysiology of delirium in the intensive care unit. Crit Care Clin 2008; 24: 45-65.
58. Maclullich AM, Ferguson KJ, Miller T, de Rooij SE, Cunningham C. Unravelling the pathophysiology of delirium: A focus on the role of aberrant stress responses. J Psychosom Res 2008; 65: 229-238.
59. Trzepacz PT. Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Semin Clin Neuropsychiatry 2000; 5: 132-148.
60. Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci 2008; 63: 764-772.
61. Pandharipande PP, Morandi A, Adams JR, et al. Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients. Intensive Care Med 2009; 35: 1886-1892.
62. Zampieri FG, Park M, Machado FS, Azevedo LC. Sepsis-associated encephalopathy: not just delirium. Clinics (Sao Paulo) 2011; 66: 1825-1831.
63. Hall RJ, Shenkin SD, Maclullich AM. A Systematic literature review of cerebrospinal fluid biomarkers in delirium. Dement Geriatr Cogn Disord 2011; 32: 79-93.
64. Mu DL, Wang DX, Li LH, et al. High serum cortisol level is associated with increased risk of delirium after coronary artery bypass graft surgery: a prospective cohort study. Crit Care 2010; 14: R238.
65. Plaschke K, Fichtenkamm P, Schramm C, et al. Early postoperative delirium after open-heart cardiac surgery is associated with decreased bispectral EEG and increased cortisol and interleukin-6. Intensive Care Med 2010; 36: 2081-2089.
66. McGrane S, Girard TD, Thompson JL, et al. Procalcitonin and C-reactive protein levels at admission as predictors of duration of acute brain dysfunction in critically ill patients. Crit Care 2011; 15: R78.
67. Soiza RL, Sharma V, Ferguson K, Shenkin SD, Seymour DG, Maclullich AM. Neuroimaging studies of delirium: A systematic review. J Psychosom Res 2008; 65: 239-248.
68. Morandi A, Gunther ML, Vasilevskis EE, et al. Neuroimaging in delirious intensive care unit patients: a preliminary case series report. Psychiatry (Edgmont) 2010; 7: 28-33.
69. Ely EW, Stephens RK, Jackson JC, et al. Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals. Crit Care Med 2004; 32: 106-112.
70. Patel RP, Gambrell M, Speroff T, et al. Delirium and sedation in the intensive care unit: survey of behaviors and attitudes of 1384 healthcare professionals. Crit Care Med 2009; 37: 825-832.
71. Mac Sweeney R, Barber V, Page V, et al. A national survey of the management of delirium in UK intensive care units. QJM 2010; 103: 243-251.
72. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc 2005; 53: 1658-1666.
73. Milbrandt EB, Kersten A, Kong L, et al. Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med 2005; 33: 226-229.
74. Lacasse H, Perreault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients. Ann Pharmacother 2006; 40: 1966-1973.
75. Seitz DP, Gill SS, van Zyl LT. Antipsychotics in the treatment of delirium: a systematic review. J Clin Psychiatry 2007; 68: 11-21.
76. Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database Syst Rev 2007;(2): CD005594.
77. 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.
78. Wolkin A, Brodie JD, Barouche F, et al. Dopamine receptor occupancy and plasma haloperidol levels. Arch Gen Psychiatry 1989; 46: 482-484.
79. Bishara D, Taylor D. Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. Drugs 2008; 68: 2269-2292.
80. Kapur S, Remington G, Jones C, et al. High levels of dopamine d2 receptor occupancy with low-dose haloperidol treatment: a pet study. Am J Psychiatry 1996; 153: 948-950.
81. Tauscher J, Kufferle B, Asenbaum S, Tauscher-Wisniewski S, Kasper S. Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. Psychopharmacology (Berl) 2002; 162: 42-49.
82. Song C, Lin A, Kenis G, Bosmans E, Maes M. Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. Schizophr Res 2000; 42: 157-164.
83. Schmidt AW, Lebel LA, Howard HR Jr., Zorn SH. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol 2001; 425: 197-201.
84. Cosi C, Waget A, Rollet K, Tesori V, Newman-Tancredi A. Clozapine, ziprasidone and aripiprazole but not haloperidol protect against kainic acid-induced lesion of the striatum in mice, in vivo: role of 5-HT1A receptor activation. Brain Res 2005; 1043: 32-41.
85. Meltzer HY, Massey BW. The role of serotonin receptors in the action of atypical antipsychotic drugs. Curr Opin Pharmacol 2011; 11: 59-67.
86. Kudo S, Ishizaki T. Pharmacokinetics of haloperidol: an update. Clin Pharmacokinet 1999; 37: 435-456.
87. Riker R, Fraser G, Cox P. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med 1994; 22: 433-440.
88. Wang W, Li HL, Wang DX, et al. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized controlled trial. Crit Care Med 2011; xx: xx-xx.
89. Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med 2004; 30: 444-449.
90. Lee KU, Won WY, Lee HK, et al. Amisulpride versus quetiapine for the treatment of delirium: a randomized, open prospective study. Int Clin Psychopharmacol 2005; 20: 311-314.
91. Pae CU, Lee SJ, Lee CU, Lee C, Paik IH. A pilot trial of quetiapine for the treatment of patients with delirium. Hum Psychopharmacol 2004; 19: 125-127.
92. Nasrallah HA, White T, Nasrallah AT. Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data. Am J Geriatr Psychiatry 2004; 12: 437-439.
93. Han CS, Kim YK. A double-blind trial of risperidone and haloperidol for the treatment of delirium. Psychosomatics 2004; 45: 297-301.
94. Grover S, Kumar V, Chakrabarti S. Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium. J Psychosom Res 2011; 71: 277-281.
95. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010; 38: 419-427.
96. Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 2010; 38: 428-437.
97. Tran PV, Dellva MA, Tollefson GD, Beasley CM Jr., Potvin JH, Kiesler GM. Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia. J Clin Psychiatry 1997; 58: 205-211.
98. Riker RB, Fraser GL, Richen P. Movement disorders associated with withdrawal from high-dose intravenous haloperidol therapy in delirious icu patients. Chest 1997; 111: 1778-1781.
99. Zornberg GL, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet 2000; 356: 1219-1223.
100. Miyaji S, Yamamoto K, Hoshino S, Yamamoto H, Sakai Y, Miyaoka H. Comparison of the risk of adverse events between risperidone and haloperidol in delirium patients. Psychiatry Clin Neurosci 2007; 61: 275-282.
101. Lee PE, Sykora K, Gill SS, et al. Antipsychotic medications and drug-induced movement disorders other than parkinsonism: a population-based cohort study in older adults. J Am Geriatr Soc 2005; 53: 1374-1379.
102. Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009; 360: 225-235.
103. Nielsen J, Bruhn AM. Atypical neuroleptic malignant syndrome caused by olanzapine. Acta Psychiatr Scand 2005; 112: 238-240.
104. Lindenmayer JP, Czobor P, Volavka J, et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry 2003; 160: 290-296.
105. Liperoti R, Pedone C, Lapane KL, Mor V, Bernabei R, Gambassi G. Venous thromboembolism among elderly patients treated with atypical and conventional antipsychotic agents. Arch Intern Med 2005; 165: 2677-2682.
106. Rochon PA, Stukel TA, Sykora K, et al. Atypical antipsychotics and parkinsonism. Arch Intern Med 2005; 165: 1882-1888.
107. Rosencheck R, Perlick D, Bingham S, et al. Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. JAMA 2003; 290: 2693-2702.
108. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009; 373: 31-41.
109. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med 2006; 355: 1525-1538.
110. Ballard C, Hanney ML, Theodoulou M, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow up on a randomised placebo-controlled trial. Lancet Neurol 2009; 8: 151-157.
111. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005; 353: 2335-2341.
112. Kuehn BM. FDA warns antipsychotic drugs may be risky for elderly. JAMA 2005; 293: 2462.
113. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294: 1934-1943.
114. Gill SS, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007; 146: 775-786.
115. Tyrer P, Kendall T. The spurious advance of antipsychotic drug therapy. Lancet 2009; 373: 4-5.
116. Liperoti R, Gambassi G, Lapane KL, et al. Conventional and atypical antipsychotics and the risk of hospitalization for ventricular arrhythmias or cardiac arrest. Arch Intern Med 2005; 165: 696-701.
117. Glassman AH, Bigger JT. Antipsychotic drugs: prolonged QTc Interval, Torsade de Pointes, and sudded death. Am J Psychiatry 2001; 158: 1774-1784.
118. Ray WA, Meredith S, Thapa PB, Meador KG, Hall K, Murray KT. Antipsychotics and the risk of sudden cardiac death. Arch Gen Psychiatry 2001; 58: 1161-1167.
119. Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SHL. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 2000; 355: 1048-1052.
120. Sharma ND, Rosman HS, Padhi ID, Tisdale JE. Torsades de Pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol 1998; 81: 238-240.
121. Harrigan EP, Miceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol 2004; 24: 62-69.
122. Straus SM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Intern Med 2004; 164: 1293-1297.
123. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350: 1013-1022.
124. Hatta K, Takahashi T, Nakamura H, et al. The association between intravenous haloperidol and the prolonged QT interval. J Clin Psychopharmacol 2001; 21: 257-261.
125. van Eijk MM, van Marum RJ, Klijn IA, de WN, Kesecioglu J, Slooter AJ. Comparison of delirium assessment tools in a mixed intensive care unit. Crit Care Med 2009; 37: 1881-1885.
126. Gregoretti C, Moglia B, Pelosi P, Navalesi P. Clonidine in perioperative medicine and intensive care unit: more than an anti-hypertensive drug. Current Drug Targets 2009; 10: 667-686.
127. Panzer O, Moitra V, Sladen RN. Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Crit Care Clin 2009; 25: 451-469.
128. Ma D, Hossain M, Rajakumaraswamy N, et al. Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype. Eur J Pharmacol 2004; 502: 87-97.
129. Kamibayashi T, Maze M. Clinical uses of alpha2 -adrenergic agonists. Anesthesiology 2000; 93: 1345-1349.
130. Hsu YW, Cortinez LI, Robertson KM, et al. Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 2004; 101: 1066-1076.
131. Prielipp RC, Wall MH, Tobin JR, et al. Dexmedetomidine-induced sedation in volunteers decreases regional and global cerebral blood flow. Anesth Analg 2002; 95: 1052-1059.
132. Pandharipande PP, Sanders RD, Girard TD, et al. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care 2010; 14: R38.
133. Shehabi Y, Grant P, Wolfenden H, et al. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (dexmedetomidine compared to morphine-dexcom study). Anesthesiology 2009; 111: 1075-1084.
134. Ruokonen E, Parviainen I, Jakob SM, et al. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med 2009; 35: 282-290.
135. Mirski MA, Lewin JJ III, Ledroux S, et al. Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: the Acute Neurological ICU Sedation Trial (ANIST). Intensive Care Med 2010; 36: 1505-1513.
136. Reade MC, O'Sullivan K, Bates S, Goldsmith D, Ainslie WR, Bellomo R. Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit Care 2009; 13: R75.
137. Gabor JY, Cooper AB, Crombach SA, et al. Contribution of the intensive care unit environment to sleep disruption in mechanically ventilated patients and healthy subjects. Am J Respir Crit Care Med 2003; 167: 708-715.
138. Weinhouse GL, Schwab RJ, Watson PL, et al. Bench-to-bedside review: Delirium in ICU patients - importance of sleep deprivation. Crit Care 2009; 13: 234.
139. 2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003; 98: 428-436.
140. Dasta JF, Kane-Gill SL, Pencina M, et al. A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit. Crit Care Med 2010; 38: 497-503.
141. Gaudreau JD, Gagnon P, Roy MA, Harel F, Tremblay A. Opioid medications and longitudinal risk of delirium in hospitalized cancer patients. Cancer 2007; 109: 2365-2373.
142. Overshott R, Karim S, Burns A. Cholinesterase inhibitors for delirium. Cochrane Database Syst Rev. 2008;(1): CD005317.
143. 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; 376: 1829-1837.
144. Morandi A, Hughes CG, Girard TD, McAuley DF, Ely EW, Pandharipande PP. Statins and brain dysfunction: a hypothesis to reduce the burden of cognitive impairment in patients who are critically ill. Chest 2011; 140: 580-585.
145. Famer D, Wahlund LO, Crisby M. Rosuvastatin reduces microglia in the brain of wild type and ApoE knockout mice on a high cholesterol diet; implications for prevention of stroke and AD. Biochem Biophys Res Commun 2010; 402: 367-372.
146. Townsend KP, Shytle DR, Bai Y, et al. Lovastatin modulation of microglial activation via suppression of functional CD40 expression. J Neurosci Res 2004; 78: 167-176.
147. Katznelson R, Djaiani GN, Borger MA, et al. Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology 2009; 110: 67-73.
148. Inouye SK, Baker DI, Fugal P, Bradley EH. Dissemination of the hospital elder life program: implementation, adaptation, and successes. J Am Geriatr Soc 2006; 54: 1492-1499.
149. Lundstrom M, Edlund A, Karlsson S, Brannstrom B, Bucht G, Gustafson Y. A multifactorial intervention program reduces the duration of delirium, length of hospitalization, and mortality in delirious patients. J Am Geriatr Soc 2005; 53: 622-628.
150. Milisen K, Lemiengre J, Braes T, Foreman MD. Multicomponent intervention strategies for managing delirium in hospitalized older people: systematic review. J Adv Nurs 2005; 52: 79-90.
151. Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: 1471-1477.
152. Kress JP, Gehlbach B, Lacy M, Pliskin N, Pohlman AS, Hall JB. The long-term psychological effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med 2003; 168: 1457-1461.
153. Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335: 1864-1869.
154. King MS, Render ML, Ely EW, Watson PL. Liberation and animation: strategies to minimize brain dysfunction in critically ill patients. Semin Respir Crit Care Med 2010; 31: 87-96.
155. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373: 1874-1882.
156. Girard TD, Shintani AK, Jackson JC, et al. Risk factors for posttraumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study. Crit Care 2007; 11: R28.
157. Jackson JC, Hart RP, Gordon SM, Hopkins RO, Girard TD, Ely EW. Post-traumatic stress disorder and post-traumatic stress symptoms following critical illness in medical intensive care unit patients: assessing the magnitude of the problem. Crit Care 2007; 11: R27.
158. Shehabi Y, Riker RR, Bokesch PM, Wisemandle W, Shintani A, Ely EW. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care unit patients. Crit Care Med 2010; 38: 2311-2318.