Delirium Management in the ICU

  • Michael E. ReznikEmail author
  • Arjen J. C. Slooter
Critical Care Neurology (H Hinson, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Critical Care Neurology


Purpose of review

Delirium occurs frequently in critically ill patients and is associated with adverse outcomes in both the short and long term. In this review, we aim to highlight recent study findings on the prevention and treatment of delirium, provide additional recommendations based on expert guidelines, and indicate knowledge gaps deserving of future study.

Recent findings

Multicomponent non-pharmacologic interventions have been shown to be efficacious in non-ICU populations, and multicomponent strategies such as the ABCDEF bundle have been adopted in the ICU with several studies showing a potential benefit in delirium outcomes. Meanwhile, two negative randomized clinical trials of antipsychotics in ICU patients (REDUCE and MIND-USA) have provided strong evidence that such medications neither prevent nor shorten the duration of delirium. Other potential pharmacologic treatments with promising results include dexmedetomidine and, to a lesser extent, ramelteon, but more data is needed before they may be more definitively recommended.


Effective and proven delirium management strategies are still largely lacking, though there is evidence to support the use of some non-pharmacologic interventions. Future studies of novel non-pharmacologic interventions and pharmacologic agents other than antipsychotics are warranted.


ICU delirium Delirium management 


Compliance with Ethical Standards

Conflict of Interest

Michael E. Reznik declares no potential conflicts of interest.

Arjen J.C. Slooter reports grants and non-financial support from Prolira, a start-up company that develops an EEG-based delirium monitor. Dr. Slooter is an advisor for Prolira. Any (future) profits from EEG-based delirium monitoring will be used for future scientific research only. In addition, Dr. Slooter has a patent “Method and system for determining a parameter which is indicative for whether a patient is delirious” (application no.: PCT/EP2013/069521, Filed September 19, 2013); pending.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Salluh JIF, Wang H, Schneider EB, Nagaraja N, Yenokyan G, Damluji A, et al. Outcome of delirium in critically ill patients: systematic review and meta-analysis. The BMJ. 2015;350:h2538. Scholar
  2. 2.
    Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L. 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. Scholar
  3. 3.
    Ely E, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753–62. Scholar
  4. 4.
    Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513–20. Scholar
  5. 5.
    van den Boogaard M, Schoonhoven L, Evers AWM, 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. Scholar
  6. 6.
    Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306–16. Scholar
  7. 7.
    Klein Klouwenberg PMC, Zaal IJ, Spitoni C, Ong DSY, van der Kooi AW, Bonten MJM, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ : British Medical Journal. 2014;349:g6652. Scholar
  8. 8.
    Wolters AE, van Dijk D, Pasma W, Cremer OL, Looije MF, de Lange DW, et al. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit Care. 2014;18(3):R125. Scholar
  9. 9.
    Fong TG, Davis D, Growdon ME, Albuquerque A, Inouye SK. The Interface of delirium and dementia in older persons. The Lancet Neurology. 2015;14(8):823–32. Scholar
  10. 10.
    Tow A, Holtzer R, Wang C, Sharan A, Kim SJ, Gladstein A, et al. Cognitive reserve and postoperative delirium in older adults. J Am Geriatr Soc. 2016;64(6):1341–6. Scholar
  11. 11.
    Cizginer S, Marcantonio E, Vasunilashorn S, Pascual-Leone A, Shafi M, Schmitt EM, et al. The cognitive reserve model in the development of delirium: the successful aging after elective surgery study. J Geriatr Psychiatry Neurol. 2017;30(6):337–45. Scholar
  12. 12.
    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(7):764–72. Scholar
  13. 13.
    Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21(12):1190–222. Scholar
  14. 14.
    van Dellen E, van der Kooi AW, Numan T, Koek HL, Klijn FA, Buijsrogge MP, et al. Decreased functional connectivity and disturbed directionality of information flow in the electroencephalography of intensive care unit patients with delirium after cardiac surgery. Anesthesiology. 2014;121(2):328–35. Scholar
  15. 15.
    Munster BCV, Aronica E, Zwinderman AH, Eikelenboom P, Cunningham C, Rooij SE. Neuroinflammation in delirium: a postmortem case-control study. Rejuvenation Res. 2011;14(6):615–22. Scholar
  16. 16.
    Diagnostic and statistical manual of mental disorders: DSM-5. Fifth edition. Arlington : American Psychiatric Association, (2013); 2013.Google Scholar
  17. 17.
    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(5):859–64.CrossRefGoogle Scholar
  18. 18.
    Eijk MMV, Boogaard MVD, Marum RJV, Benner P, Eikelenboom P, Honing ML, et al. Routine use of the confusion assessment method for the intensive care unit. Am J Respir Crit Care Med. 2011;184(3):340–4. Scholar
  19. 19.
    Morandi A, Davis D, Bellelli G, Arora RC, Caplan GA, Kamholz B, et al. The diagnosis of delirium superimposed on dementia: an emerging challenge. J Am Med Dir Assoc. 2017;18(1):12–8. Scholar
  20. 20.
    Inouye SK, Leo-Summers L, Zhang Y, Bogardus ST Jr, Leslie DL, Agostini JV. A chart-based method for identification of delirium: validation compared with interviewer ratings using the confusion assessment method. J Am Geriatr Soc. 2005;53(2):312–8. Scholar
  21. 21.
    Ahmed S, Leurent B, Sampson EL. Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis. Age Ageing. 2014;43(3):326–33. Scholar
  22. 22.
    Zaal IJ, Devlin JW, Peelen LM, Slooter AJC. A systematic review of risk factors for delirium in the ICU*. Crit Care Med. 2015;43(1):40–7. Scholar
  23. 23.
    Wassenaar A, van den Boogaard M, van Achterberg T, Slooter AJC, Kuiper MA, Hoogendoorn ME, et al. Multinational development and validation of an early prediction model for delirium in ICU patients. Intensive Care Med. 2015;41(6):1048–56. Scholar
  24. 24.
    van den Boogaard M, Pickkers P, Slooter AJC, Kuiper MA, Spronk PE, van den Voort PHJ, et al. Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study. BMJ. 2012;344:e420. Scholar
  25. 25.
    Inouye SK, Bogardus ST, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669–76. Scholar
  26. 26.
    Hshieh TT, Yang T, Gartaganis SL, Yue J, Inouye SK. Hospital elder life program: systematic review and meta-analysis of effectiveness. Am J Geriatr Psychiatry. 2018;26(10):1015–33. Scholar
  27. 27.
    Hshieh TT, Yue J, Oh E, Puelle M, Dowal S, Travison T, et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis of delirium prevention. JAMA Intern Med. 2015;175(4):512–20. Scholar
  28. 28.
    Siddiqi N, Harrison JK, Clegg A, Teale EA, Young J, Taylor J, et al. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2016;(3).
  29. 29.
    Bannon L, Mc Gaughey J, Verghis R, Clarke M, Mc Auley DF, Blackwood B. The effectiveness of non-pharmacological interventions in reducing the incidence and duration of delirium in critically ill patients: a systematic review and meta-analysis. Intensive Care Med. 2018;45(1):1–12. A comprehensive systematic review and meta-analysis of clinical studies for single- and multi-component non-pharmacological interventions to prevent delirium in ICU patients.CrossRefGoogle Scholar
  30. 30.
    Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825–e73. A wide-ranging and recently updated set of clinical practice guidelines on the management of delirium and delirium-related issues in the ICU by the Society for Critical Care Medicine.CrossRefPubMedGoogle Scholar
  31. 31.
    Marra A, Ely EW, Pandharipande PP, Patel MB. The ABCDEF bundle in critical care. Crit Care Clin. 2017;33(2):225–43. Scholar
  32. 32.
    Balas MC, Vasilevskis EE, Olsen KM, Schmid KK, Shostrom V, Cohen MZ, et al. Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle*. Crit Care Med. 2014;42(5):1024–36. Scholar
  33. 33.
    Barnes-Daly MA, Phillips G, Ely EW. Improving hospital survival and reducing brain dysfunction at seven California community hospitals: implementing PAD guidelines via the ABCDEF bundle in 6,064 patients*. Crit Care Med. 2017;45(2):171–8. Scholar
  34. 34.
    Pun BT, Balas MC, Barnes-Daly MA, Thompson JL, Aldrich JM, Barr J, et al. Caring for critically ill patients with the ABCDEF bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med. 2019;47(1):3–14. A large prospective multi-center quality improvement study showing that ABCDEF bundle adherence was associated with improved ICU outcomes, including a lower likelihood of delirium.CrossRefPubMedGoogle Scholar
  35. 35.
    Morandi A, Piva S, Ely EW, Myatra SN, Salluh JIF, Amare D, et al. Worldwide survey of the “Assessing pain, both spontaneous awakening and breathing trials, choice of drugs, delirium monitoring/management, early exercise/mobility, and family empowerment” (ABCDEF). Bundle Critical Care Medicine. 2017;45(11):e1111–e22. Scholar
  36. 36.
    Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009;373(9678):1874–82. Scholar
  37. 37.
    Álvarez EA, Garrido MA, Tobar EA, Prieto SA, Vergara SO, Briceño CD, et al. Occupational therapy for delirium management in elderly patients without mechanical ventilation in an intensive care unit: a pilot randomized clinical trial. J Crit Care. 2017;37:85–90. Scholar
  38. 38.
    Zaal IJ, Spruyt CF, Peelen LM, van Eijk MMJ, Wientjes R, Schneider MME, et al. Intensive care unit environment may affect the course of delirium. Intensive Care Med. 2013;39(3):481–8. Scholar
  39. 39.
    Litton E, Carnegie V, Elliott R, Webb SAR. The efficacy of earplugs as a sleep hygiene strategy for reducing delirium in the ICU: a systematic review and meta-analysis*. Crit Care Med. 2016;44(5):992–9. Scholar
  40. 40.
    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. JAMA Intern Med. 2007;167(13):1406–13. Scholar
  41. 41.
    Colombo R, Corona A, Praga F, Minari C, Giannotti C, Castelli A, et al. A reorientation strategy for reducing delirium in the critically ill. Results of an interventional study. Minerva Anestesiol. 2012;78(9):1026–33.PubMedGoogle Scholar
  42. 42.
    Munro CL, Cairns P, Ji M, Calero K, Anderson WM, Liang Z. Delirium prevention in critically ill adults through an automated reorientation intervention: a pilot randomized controlled trial. Heart & Lung: The Journal of Cardiopulmonary and Acute Care. 2017;46(4):234–8. Scholar
  43. 43.
    Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. 2001;49(5):516–22. Scholar
  44. 44.
    Björkelund KB, Hommel A, Thorngren K-G, Gustafson L, Larsson S, Lundberg D. Reducing delirium in elderly patients with hip fracture: a multi-factorial intervention study. Acta Anaesthesiol Scand. 2010;54(6):678–88. Scholar
  45. 45.
    Trzepacz PT. Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Semin Clin Neuropsychiatry. 2000;5(2):132–48.Google Scholar
  46. 46.
    van den Boogaard M, Slooter AJC, Brüggemann RJM, Schoonhoven L, Beishuizen A, Vermeijden JW, et al. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the REDUCE randomized clinical trial. JAMA. 2018;319(7):680–90. One of two recent randomized clinical trials that found that antipsychotics—in this case haloperidol—were ineffective in ICU patients. This study showed that delirium could not be prevented with haloperidol.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Girard TD, Exline MC, Carson SS, Hough CL, Rock P, Gong MN, et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018;379(26):2506–16. One of two recent randomized clinical trials that found that antipsychotics—in this case haloperidol and ziprasidone—were ineffective in ICU patients. This study showed that delirium duration could not be shorted with antipsychotics.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64(4):705–14. A comprehensive systematic review and meta-analysis of clinical studies for the use of antipsychotics to prevent and treat delirium in hospitalized patients.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Young J, Murthy L, Westby M, Akunne A, O’Mahony R. Diagnosis, prevention, and management of delirium: summary of NICE guidance. BMJ. 2010;341:c3704. Scholar
  50. 50.
    Siafis S, Tzachanis D, Samara M, Papazisis G. Antipsychotic drugs: from receptor-binding profiles to metabolic side effects. Curr Neuropharmacol. 2018;16(8):1210–23. Scholar
  51. 51.
    Lonergan E, Britton AM, Luxenberg J. Antipsychotics for delirium. Cochrane Database Syst Rev 2007(2). doi:
  52. 52.
    Devlin JW, Roberts RJ, Fong JJ, Skrobik Y, Riker RR, Hill NS, 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(2):419–27. Scholar
  53. 53.
    Hawkins SB, Bucklin M, Muzyk AJ. Quetiapine for the treatment of delirium. J Hosp Med. 2013;8(4):215–20. Scholar
  54. 54.
    Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med. 2004;30(3):444–9. Scholar
  55. 55.
    Liptzin B, Laki A, Garb JL, Fingeroth R, Krushell R. Donepezil in the prevention and treatment of post-surgical delirium. Am J Geriatr Psychiatry. 2005;13(12):1100–6. Scholar
  56. 56.
    Sampson EL, Raven PR, Ndhlovu PN, Vallance A, Garlick N, Watts J, et al. A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement. Int J Geriatric Psychiatry. 2007;22(4):343–9. Scholar
  57. 57.
    Marcantonio ER, Palihnich K, Appleton P, Davis RB. Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture. J Am Geriatr Soc. 2011;59(s2):S282–S8. Scholar
  58. 58.
    van Eijk MMJ, Roes KCB, Honing MLH, Kuiper MA, Karakus A, van der Jagt M, 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(9755):1829–37. Scholar
  59. 59.
    Patel SB, Poston JT, Pohlman A, Hall JB, Kress JP. Rapidly reversible, sedation-related delirium versus persistent delirium in the intensive care unit. Am J Respir Crit Care Med. 2014;189(6):658–65. Scholar
  60. 60.
    Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186(8):724–31. Scholar
  61. 61.
    Shehabi Y, Chan L, Kadiman S, Alias A, Ismail WN, Tan MATI, et al. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med. 2013;39(5):910–8. Scholar
  62. 62.
    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(20):1471–7. Scholar
  63. 63.
    Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, 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(9607):126–34. Scholar
  64. 64.
    Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;308(19):1985–92. Scholar
  65. 65.
    Zaal IJ, Devlin JW, Hazelbag M, Klein Klouwenberg PMC, van der Kooi AW, Ong DSY, et al. Benzodiazepine-associated delirium in critically ill adults. Intensive Care Med. 2015;41(12):2130–7. Scholar
  66. 66.
    Pisani MA, Murphy TE, Araujo KLB, 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(1):177–83. Scholar
  67. 67.
    Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2006;104(1):21–6.CrossRefGoogle Scholar
  68. 68.
    Pandharipande P, Cotton BA, Shintani A, Thompson J, Pun BT, Morris JAJ, et al. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma Acute Care Surg. 2008;65(1):34–41. Scholar
  69. 69.
    Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, 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(22):2644–53. Scholar
  70. 70.
    Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489–99. Scholar
  71. 71.
    Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151–60. Scholar
  72. 72.
    Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-dose nocturnal dexmedetomidine prevents ICU delirium. A randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2018;197(9):1147–56. Scholar
  73. 73.
    Deiner S, Luo X, Lin H-M, Sessler DI, Saager L, Sieber FE, et al. Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial. JAMA Surgery. 2017;152(8):e171505. Scholar
  74. 74.
    Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315(14):1460–8. A randomized clinical trial that found dexmedetomidine was effective in shortening the duration of delirium in agitated ICU patients when added to standard care.CrossRefPubMedGoogle Scholar
  75. 75.
    Gagnon DJ, Riker RR, Glisic EK, Kelner A, Perrey HM, Fraser GL. Transition from dexmedetomidine to enteral clonidine for ICU sedation: an observational pilot study. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2015;35(3):251–9. Scholar
  76. 76.
    Morrison RS, Magaziner J, Gilbert M, Koval KJ, McLaughlin MA, Orosz G, et al. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol: Series A. 2003;58(1):M76–81. Scholar
  77. 77.
    Feast AR, White N, Lord K, Kupeli N, Vickerstaff V, Sampson EL. Pain and delirium in people with dementia in the acute general hospital setting. Age Ageing. 2018;47(6):841–6. Scholar
  78. 78.
    Marcantonio ER, Juarez G, Goldman L, Mangione CM, Ludwig LE, Lind L, et al. The relationship of postoperative delirium with psychoactive medications. JAMA. 1994;272(19):1518–22. Scholar
  79. 79.
    Subramaniam B, Shankar P, Shaefi S, Mueller A, O’Gara B, Banner-Goodspeed V, et al. Effect of intravenous acetaminophen vs placebo combined with propofol or dexmedetomidine on postoperative delirium among older patients following cardiac surgery: the DEXACET randomized clinical trial. JAMA. 2019;321(7):686–96. A randomized clinical trial that found scheduled intravenous acetaminophen was effective in preventing post-operative delirium, emphasizing the importance of nonopioid analgesia in delirium management.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Abou-Setta AM, Beaupre LA, Rashiq S, Dryden DM, Hamm MP, Sadowski CA, et al. Comparative effectiveness of pain management interventions for hip fracture: a systematic review. Ann Intern Med. 2011;155(4):234–45. Scholar
  81. 81.
    Erstad BL, Patanwala AE. Ketamine for analgosedation in critically ill patients. J Crit Care. 2016;35:145–9. Scholar
  82. 82.
    Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, et al. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009;23(5):651–7. Scholar
  83. 83.
    Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, et al. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017;390(10091):267–75. Scholar
  84. 84.
    Wesselius HM, van den Ende ES, Alsma J, ter Maaten JC, Schuit SCE, Stassen PM, et al. Quality and quantity of sleep and factors associated with sleep disturbance in hospitalized patients. JAMA Intern Med. 2018;178(9):1201–8. Scholar
  85. 85.
    Evans JL, Nadler JW, Preud'homme XA, Fang E, Daughtry RL, Chapman JB, et al. Pilot prospective study of post-surgery sleep and EEG predictors of post-operative delirium. Clin Neurophysiol. 2017;128(8):1421–5. Scholar
  86. 86.
    de Jonghe A, van Munster BC, Goslings JC, Kloen P, van Rees C, Wolvius R, et al. Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial. Can Med Assoc J. 2014;186(14):E547–E56. Scholar
  87. 87.
    Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. In J Geriatric Psychiatry. 2011;26(7):687–94. Scholar
  88. 88.
    Hatta K, Kishi Y, Wada K, Takeuchi T, Odawara T, Usui C, et al. Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry. 2014;71(4):397–403. Scholar
  89. 89.
    Nishikimi M, Numaguchi A, Takahashi K, Miyagawa Y, Matsui K, Higashi M, et al. Effect of administration of ramelteon, a melatonin receptor agonist, on the duration of stay in the ICU: a single-center randomized placebo-controlled trial*. Crit Care Med. 2018;46(7):1099–105. Scholar
  90. 90.
    Gillis CM, Poyant JO, Degrado JR, Ye L, Anger KE, Owens RL. Inpatient pharmacological sleep aid utilization is common at a tertiary medical center. J Hosp Med. 2014;9(10):652–7. Scholar
  91. 91.
    American Geriatrics Society 2015. Updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46. Scholar
  92. 92.
    Roehrs T, Roth T. Drug-related sleep stage changes: functional significance and clinical relevance. Sleep Med Clin. 2010;5(4):559–70. Scholar
  93. 93.
    Han L, McCusker J, Cole M, Abrahamowicz M, Primeau F, Élie M. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. JAMA Intern Med. 2001;161(8):1099–105. Scholar
  94. 94.
    Schreiber MP, Colantuoni E, Bienvenu OJ, Neufeld KJ, Chen K-F, Shanholtz C, et al. Corticosteroids and transition to delirium in patients with acute lung injury*. Crit Care Med. 2014;42(6):1480–6. Scholar
  95. 95.
    Patel MB, Bednarik J, Lee P, Shehabi Y, Salluh JI, Slooter AJ, et al. Delirium monitoring in neurocritically ill patients: a systematic review*. Crit Care Med. 2018;46(11):1832–41. Scholar
  96. 96.
    Shi Q, Presutti R, Selchen D, Saposnik G. Delirium in acute stroke: a systematic review and meta-analysis. Stroke. 2012;43(3):645–9. Scholar
  97. 97.
    Reznik ME, Drake J, Margolis SA, Moody S, Murray K, Costa S et al. Deconstructing post-stroke delirium in a prospective cohort of patients with intracerebral hemorrhage. Critical Care Med 2019;Publication pending.Google Scholar
  98. 98.
    Frenette AJ, Bebawi ER, Deslauriers LC, Tessier A-AL, Perreault MM, Delisle M-S, et al. Validation and comparison of CAM-ICU and ICDSC in mild and moderate traumatic brain injury patients. Intensive Care Med. 2016;42(1):122–3. Scholar
  99. 99.
    Larsen LK, Frøkjær VG, Nielsen JS, Skrobik Y, Winkler Y, Møller K, et al. Delirium assessment in neuro-critically ill patients: a validation study. Acta Anaesthesiol Scand. 2019;63(3):352–9. Scholar
  100. 100.
    Frontera JA. Delirium and sedation in the ICU. Neurocrit Care. 2011;14(3):463–74. Scholar
  101. 101.
    Reznik ME, Schmidt JM, Mahta A, Agarwal S, Roh DJ, Park S, et al. Agitation after subarachnoid hemorrhage: a frequent omen of hospital complications associated with worse outcomes. Neurocrit Care. 2016;26:1–8. Scholar
  102. 102.
    McLaughlin DC, Hartjes TM, Freeman WD. Sleep deprivation in neurointensive care unit patients from serial neurological checks: how much is too much? J Neurosci Nurs. 2018;50(4):205–10. Scholar
  103. 103.
    Mirski MA, Lewin JJ, LeDroux S, Thompson C, Murakami P, Zink EK, 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(9):1505–13. Scholar
  104. 104.
    Tran A, Blinder H, Hutton B, English SW. A systematic review of alpha-2 agonists for sedation in mechanically ventilated neurocritical care patients. Neurocrit Care. 2018;28(1):12–25. Scholar
  105. 105.
    Feeney D, Gonzalez A, Law W. Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science. 1982;217(4562):855–7. Scholar
  106. 106.
    Goldstein LB, Bullman S. Differential effects of haloperidol and clozapine on motor recovery after sensorimotor cortex injury in rats. Neurorehabil Neural Repair. 2002;16(4):321–5. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departments of Neurology & Neurosurgery, Alpert Medical SchoolBrown UniversityProvidenceUSA
  2. 2.Division of Neurocritical CareRhode Island HospitalProvidenceUSA
  3. 3.Department of Intensive Care Medicine, University Medical Center Utrecht Brain CenterUtrecht UniversityUtrechtthe Netherlands

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