Neurocritical Care

, Volume 14, Issue 3, pp 463–474 | Cite as

Delirium and Sedation in the ICU

  • Jennifer A. Frontera


Delirium is defined by a fluctuating level of attentiveness and has been associated with increased ICU mortality and poor cognitive outcomes in both general ICU and neurocritical care populations. Sedation use in the ICU can contribute to delirium. Limiting ICU sedation allows for the diagnosis of underlying acute neurological insults associated with delirium and leads to shorter mechanical ventilation time, shorter length of stay, and improved 1 year mortality rates. Identifying the underlying etiology of delirium is critical to developing treatment paradigms.


Delirium Sedation ICU Intensive care Confusion Neurocritical care 


Conflict of interest



  1. 1.
    American Psychiatric Association. Diagnostic and statistical manual. 4th ed. Washington, DC: APA Press; 1994.Google Scholar
  2. 2.
    Kiely DK, Bergmann MA, Murphy KM, Jones RN, Orav EJ, Marcantonio ER. Delirium among newly admitted postacute facility patients: prevalence, symptoms, and severity. J Gerontol A Biol Sci Med Sci. 2003;58:M441–5.PubMedGoogle Scholar
  3. 3.
    Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Arch Intern Med. 2000;160:786–94.PubMedCrossRefGoogle Scholar
  4. 4.
    McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc. 2003;51:591–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Dyer CB, Ashton CM, Teasdale TA. Postoperative delirium. A review of 80 primary data-collection studies. Arch Intern Med. 1995;155:461–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Francis J. Delirium in older patients. J Am Geriatr Soc. 1992;40:829–38.PubMedGoogle Scholar
  7. 7.
    Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med. 1998;13:234–42.PubMedCrossRefGoogle Scholar
  8. 8.
    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;291:1753–62.PubMedCrossRefGoogle Scholar
  9. 9.
    Caeiro L, Ferro JM, Albuquerque R, Figueira ML. Delirium in the first days of acute stroke. J Neurol. 2004;251:171–8.PubMedCrossRefGoogle Scholar
  10. 10.
    McManus J, Pathansali R, Hassan H, et al. The course of delirium in acute stroke. Age Ageing. 2009;38:385–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Sheng AZ, Shen Q, Cordato D, Zhang YY, Yin Chan DK. Delirium within three days of stroke in a cohort of elderly patients. J Am Geriatr Soc. 2006;54:1192–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Dysken MW, Skare SS, Burke MS, Mach JR Jr, Galka T, Billington CJ. Intrasubject reproducibility of growth hormone-releasing hormone-stimulated growth hormone in older women, older men, and younger men. Biol Psychiatry. 1993;33:610–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Tune L, Carr S, Cooper T, Klug B, Golinger RC. Association of anticholinergic activity of prescribed medications with postoperative delirium. J Neuropsychiatry Clin Neurosci. 1993;5:208–10.PubMedGoogle Scholar
  14. 14.
    Figueroa-Ramos MI, Arroyo-Novoa CM, Lee KA, Padilla G, Puntillo KA. Sleep and delirium in ICU patients: a review of mechanisms and manifestations. Intensive Care Med. 2009;35:781–95.PubMedCrossRefGoogle Scholar
  15. 15.
    Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol A Biol Sci Med Sci. 1999;54:B239–46.PubMedCrossRefGoogle Scholar
  16. 16.
    Stefano GB, Bilfinger TV, Fricchione GL. The immune-neuro-link and the macrophage: postcardiotomy delirium, HIV-associated dementia and psychiatry. Prog Neurobiol. 1994;42:475–88.PubMedCrossRefGoogle Scholar
  17. 17.
    Dasgupta M, Dumbrell AC. Preoperative risk assessment for delirium after noncardiac surgery: a systematic review. J Am Geriatr Soc. 2006;54:1578–89.PubMedCrossRefGoogle Scholar
  18. 18.
    Fick DM, Agostini JV, Inouye SK. Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2002;50:1723–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Inouye SK, Zhang Y, Jones RN, Kiely DK, Yang F, Marcantonio ER. Risk factors for delirium at discharge: development and validation of a predictive model. Arch Intern Med. 2007;167:1406–13.PubMedCrossRefGoogle Scholar
  20. 20.
    Lundstrom M, Edlund A, Bucht G, Karlsson S, Gustafson Y. Dementia after delirium in patients with femoral neck fractures. J Am Geriatr Soc. 2003;51:1002–6.PubMedCrossRefGoogle Scholar
  21. 21.
    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;167:1629–34.PubMedCrossRefGoogle Scholar
  22. 22.
    Rudolph JL, Jones RN, Rasmussen LS, Silverstein JH, Inouye SK, Marcantonio ER. Independent vascular and cognitive risk factors for postoperative delirium. Am J Med. 2007;120:807–13.PubMedCrossRefGoogle Scholar
  23. 23.
    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;286:2703–10.PubMedCrossRefGoogle Scholar
  24. 24.
    Francis J. Drug-induced delirium: diagnosis and treatment. Auckland: Mairangi Bay; 1996.Google Scholar
  25. 25.
    Claassen J, Mayer SA, Kowalski RG, Emerson RG, Hirsch LJ. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology. 2004;62:1743–8.PubMedGoogle Scholar
  26. 26.
    Jordan KG. Neurophysiologic monitoring in the neuroscience intensive care unit. Neurol Clin. 1995;13:579–626.PubMedGoogle Scholar
  27. 27.
    Privitera M, Hoffman M, Moore JL, Jester D. EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness. Epilepsy Res. 1994;18:155–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Vespa PM, O’Phelan K, Shah M, et al. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology. 2003;60:1441–6.PubMedGoogle Scholar
  29. 29.
    Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000;54:340–5.PubMedGoogle Scholar
  30. 30.
    Oddo M, Carrera E, Claassen J, Mayer SA, Hirsch LJ. Continuous electroencephalography in the medical intensive care unit. Crit Care Med. 2009;37:2051–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Alberts VP, Bos MJ, Koudstaal PJ, et al. Heart failure and the risk of stroke: the Rotterdam Study. Eur J Epidemiol. 2010;25:807–12.PubMedCrossRefGoogle Scholar
  32. 32.
    Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med. 1997;336:251–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Trzepacz PT, Baker RW, Greenhouse J. A symptom rating scale for delirium. Psychiatry Res. 1988;23:89–97.PubMedCrossRefGoogle Scholar
  34. 34.
    Benbadis SR, Sila CA, Cristea RL. Mental status changes and stroke. J Gen Intern Med. 1994;9:485–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Salerno D, Marik PE, Daskalakis C, Kolm P, Leone F. The role of head computer tomographic scans on the management of MICU patients with neurological dysfunction. J Intensive Care Med. 2009;24:372–5.PubMedCrossRefGoogle Scholar
  36. 36.
    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.Google Scholar
  37. 37.
    Warshaw G, Tanzer F. The effectiveness of lumbar puncture in the evaluation of delirium and fever in the hospitalized elderly. Arch Fam Med. 1993;2:293–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Inouye SK. Delirium in hospitalized older patients. Clin Geriatr Med. 1998;14:745–64.PubMedGoogle Scholar
  39. 39.
    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;166:1338–44.PubMedCrossRefGoogle Scholar
  40. 40.
    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;298:2644–53.PubMedCrossRefGoogle Scholar
  41. 41.
    Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489–99.PubMedCrossRefGoogle Scholar
  42. 42.
    Shehabi Y, Riker RR, Bokesch PM, Wisemandle W, Shintani A, Ely EW. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med. 2010;38:2311–8.PubMedCrossRefGoogle Scholar
  43. 43.
    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;371:126–34.PubMedCrossRefGoogle Scholar
  44. 44.
    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;38:1513–20.PubMedCrossRefGoogle Scholar
  45. 45.
    Adelow C, Andersson T, Ahlbom A, Tomson T. Prior hospitalization for stroke, diabetes, myocardial infarction, and subsequent risk of unprovoked seizures. Epilepsia. 2011;52(2):301–7.PubMedGoogle Scholar
  46. 46.
    Caeiro L, Ferro JM, Claro MI, Coelho J, Albuquerque R, Figueira ML. Delirium in acute stroke: a preliminary study of the role of anticholinergic medications. Eur J Neurol. 2004;11:699–704.PubMedCrossRefGoogle Scholar
  47. 47.
    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;342:1471–7.PubMedCrossRefGoogle Scholar
  48. 48.
    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;373:1874–82.PubMedCrossRefGoogle Scholar
  49. 49.
    Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375:475–80.PubMedCrossRefGoogle Scholar
  50. 50.
    Yildizeli B, Ozyurtkan MO, Batirel HF, Kuscu K, Bekiroglu N, Yuksel M. Factors associated with postoperative delirium after thoracic surgery. Ann Thorac Surg. 2005;79:1004–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Krachman SL, D’Alonzo GE, Criner GJ. Sleep in the intensive care unit. Chest. 1995;107:1713–20.PubMedCrossRefGoogle Scholar
  52. 52.
    Inouye SK, Baker DI, Fugal P, Bradley EH. Dissemination of the hospital elder life program: implementation, adaptation, and successes. J Am Geriatr Soc. 2006;54:1492–9.PubMedCrossRefGoogle Scholar
  53. 53.
    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;30:119–41.PubMedCrossRefGoogle Scholar
  54. 54.
    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;104:21–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Mayer SA, Chong JY, Ridgway E, Min KC, Commichau C, Bernardini GL. Delirium from nicotine withdrawal in neuro-ICU patients. Neurology. 2001;57:551–3.PubMedGoogle Scholar
  56. 56.
    Lucidarme O, Seguin A, Daubin C, et al. Nicotine withdrawal and agitation in ventilated critically ill patients. Crit Care. 2010;14:R58.Google Scholar
  57. 57.
    Lee AH, Afessa B. The association of nicotine replacement therapy with mortality in a medical intensive care unit. Crit Care Med. 2007;35:1517–21.PubMedCrossRefGoogle Scholar
  58. 58.
    Seder DB, Schmidt JM, Badjatia N, et al. Transdermal nicotine replacement therapy in cigarette smokers with acute subarachnoid hemorrhage. Neurocrit Care. 2011;14:77–83.PubMedCrossRefGoogle Scholar
  59. 59.
    Adams F. Emergency intravenous sedation of the delirious, medically ill patient. J Clin Psychiatry. 1988;49(Suppl):22–7.PubMedGoogle Scholar
  60. 60.
    Riker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med. 1994;22:433–40.PubMedCrossRefGoogle Scholar
  61. 61.
    Levenson JL. High-dose intravenous haloperidol for agitated delirium following lung transplantation. Psychosomatics. 1995;36:66–8.PubMedGoogle Scholar
  62. 62.
    Sanders KM, Murray GB, Cassem NH. High-dose intravenous haloperidol for agitated delirium in a cardiac patient on intra-aortic balloon pump. J Clin Psychopharmacol. 1991;11:146–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Seneff MG, Mathews RA. Use of haloperidol infusions to control delirium in critically ill adults. Ann Pharmacother. 1995;29:690–3.PubMedGoogle Scholar
  64. 64.
    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;360:225–35.PubMedCrossRefGoogle Scholar
  65. 65.
    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;294:1934–43.PubMedCrossRefGoogle Scholar
  66. 66.
    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;353:2335–41.PubMedCrossRefGoogle Scholar
  67. 67.
    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;38:428–37.PubMedCrossRefGoogle Scholar
  68. 68.
    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. 2009;38:419–27.CrossRefGoogle Scholar
  69. 69.
    Lynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio ER. The impact of postoperative pain on the development of postoperative delirium. Anesth Analg. 1998;86:781–5.PubMedGoogle Scholar
  70. 70.
    Morrison RS, Magaziner J, Gilbert M, et al. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci. 2003;58:76–81.PubMedGoogle Scholar
  71. 71.
    Holbrook TL, Galarneau MR, Dye JL, Quinn K, Dougherty AL. Morphine use after combat injury in Iraq and post-traumatic stress disorder. N Engl J Med. 2010;362:110–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Komotar RJ, Mocco J, Ransom ER, et al. Herniation secondary to critical postcraniotomy cerebrospinal fluid hypovolemia. Neurosurgery. 2005;57:286–92. (discussion 92).PubMedCrossRefGoogle Scholar
  73. 73.
    Brown CV, Zada G, Salim A, et al. Indications for routine repeat head computed tomography (CT) stratified by severity of traumatic brain injury. J Trauma. 2007;62:1339–44. (discussion 44–5).PubMedCrossRefGoogle Scholar
  74. 74.
    Medical Research Council. Aids to the examination of the peripheral nervous system, Memorandum no. 45. London: Her Majesty’s Stationary Office; 1981.Google Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Neuroscience Intensive Care Unit, Departments of Neurosurgery and NeurologyMount Sinai School of MedicineNew YorkUSA

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