Delirium and Psychosis in Critically Ill Cancer Patients

  • Kimberly F. Rengel
  • Daniel A. Nahrwold
  • Pratik P. Pandharipande
  • Christopher G. HughesEmail author
Reference work entry


Delirium is a common diagnosis within the critically ill cancer population. It is characterized by acute and rapid fluctuations in mental status and consciousness. The diagnosis of delirium can be difficult and is often accomplished with the use of a validated delirium assessment tool. The prevalence of delirium varies widely with higher rates in patients who are elderly, have severe critical illness including cancer, or are known to have preexisting cognitive impairment and dementia. The pathophysiology of delirium is highly complex and may be related to changes in the brain as a result of neuroinflammation, endothelial dysfunction, aberrant cerebral perfusion patterns, and deficiency or abnormal activity of neurotransmitters. The prevention of delirium in the critically ill involves multiple components including choice of pain and sedating medications, early physical and occupational therapy, improving sleep, and daily awakening and breathing trials. There are no FDA-approved pharmacologic treatments available for delirium, though some of the antipsychotics and dexmedetomidine have shown promise in various studies. Delirium can be a challenging and deleterious diagnosis for critically ill cancer patients, but with proper recognition, as well as validated preventative and management strategies, the negative consequences associated with delirium can be decreased.


Delirium Cancer Coma Agitation Sedation Antipsychotics Dexmedetomidine Neuroinflammation Pain Psychosis 


  1. 1.
    Agar MR, et al. Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Intern Med. 2017;177:34–42. Scholar
  2. 2.
    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. Int J Geriatr Psychiatry. 2011; 26:687–94. Scholar
  3. 3.
    Aurell J, Elmqvist D. Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in nine patients receiving postoperative care. Br Med J (Clin Res Ed). 1985;290:1029–32.CrossRefGoogle Scholar
  4. 4.
    Avidan MS, 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;390:267–75. Scholar
  5. 5.
    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;45:171–8. Scholar
  6. 6.
    Benitez-Rosario MA, Feria M, Salinas-Martin A, Martinez-Castillo LP, Martin-Ortega JJ. Opioid switching from transdermal fentanyl to oral methadone in patients with cancer pain. Cancer. 2004;101: 2866–73. Scholar
  7. 7.
    Boettger S, Jenewein J, Breitbart W. Delirium and severe illness: etiologies, severity of delirium and phenomenological differences. Palliat Support Care. 2015;13:1087–92. Scholar
  8. 8.
    Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K, Passik S. The memorial delirium assessment scale. J Pain Symptom Manage 1997;13(3):128–37.CrossRefGoogle Scholar
  9. 9.
    Breitbart W, Tremblay A, Gibson C. An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics. 2002;43:175–82. Scholar
  10. 10.
    Carrasco G, Baeza N, Cabre L, Portillo E, Gimeno G, Manzanedo D, Calizaya M. Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in nonintubated ICU patients: a nonrandomized controlled trial. Crit Care Med. 2016;44:1295–306. Scholar
  11. 11.
    Cavallari M, et al. Longitudinal diffusion changes following postoperative delirium in older people without dementia. Neurology. 2017;89:1020–7. Scholar
  12. 12.
    de Jonghe A, et al. Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial. CMAJ. 2014;186:E547–56. Scholar
  13. 13.
    Deiner S, 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 Surg. 2017;152:e171505. Scholar
  14. 14.
    Devlin JW, 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:e825–73. Scholar
  15. 15.
    Devlin JW, et al. Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study. Crit Care. 2011; 15:R215. Scholar
  16. 16.
    Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, Katznelson R. Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: a randomized controlled trial. Anesthesiology. 2016; 124:362–8. Scholar
  17. 17.
    Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction. Semin Respir Crit Care Med. 2001; 22:115–26. Scholar
  18. 18.
    Gamberini M, et al. Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery – a randomized controlled trial. Crit Care Med. 2009;37:1762–8. Scholar
  19. 19.
    Gaudreau JD, Gagnon P, Harel F, Roy MA, Tremblay A. Psychoactive medications and risk of delirium in hospitalized cancer patients. J Clin Oncol. 2005;23:6712–8. Scholar
  20. 20.
    Girard TD, 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. Scholar
  21. 21.
    Girard TD, 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.CrossRefGoogle Scholar
  22. 22.
    Gunther ML, et al. The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study*. Crit Care Med. 2012;40:2022–32. Scholar
  23. 23.
    Hatta K, et al. Preventive effects of Ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry. 2014;71:397–403. Scholar
  24. 24.
    Hilliard N, Brown S, Mitchinson S. A case report of dexmedetomidine used to treat intractable pain and delirium in a tertiary palliative care unit. Palliat Med. 2015;29:278–81. Scholar
  25. 25.
    Hirota T, Kishi T. Prophylactic antipsychotic use for postoperative delirium: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74:e1136–44. Scholar
  26. 26.
    Hudetz JA, et al. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009;23:651–7. Scholar
  27. 27.
    Hughes CG, Pandharipande PP, Thompson JL, Chandrasekhar R, Ware LB, Ely EW, Girard TD. Endothelial activation and blood-brain barrier injury as risk factors for delirium in critically ill patients. Crit Care Med. 2016;44:e809–17. Scholar
  28. 28.
    Hughes CG, Patel MB, Pandharipande PP. Pathophysiology of acute brain dysfunction: what’s the cause of all this confusion? Curr Opin Crit Care. 2012;18: 518–26. Scholar
  29. 29.
    Hui D, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial. JAMA. 2017;318:1047–56. Scholar
  30. 30.
    Keh D, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial. JAMA. 2016; 316: 1775–85. Scholar
  31. 31.
    Kim SW, et al. Risperidone versus olanzapine for the treatment of delirium. Hum Psychopharmacol. 2010;25:298–302. Scholar
  32. 32.
    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. Scholar
  33. 33.
    Lawlor PG, Nekolaichuk C, Gagnon B, Mancini IL, Pereira JL, Bruera ED. Clinical utility, factor analysis, and further validation of the memorial delirium assessment scale in patients with advanced cancer: assessing delirium in advanced cancer. Cancer. 2000;88: 2859–67.CrossRefGoogle Scholar
  34. 34.
    Liu Y, Ma L, Gao M, Guo W, Ma Y. Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment. Aging Clin Exp Res. 2016;28:729–36. Scholar
  35. 35.
    Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21:1190–222. Scholar
  36. 36.
    Marra A, Ely EW, Pandharipande PP, Patel MB. The ABCDEF bundle in critical care. Crit Care Clin. 2017;33:225–43. Scholar
  37. 37.
    Miyata R, Omasa M, Fujimoto R, Ishikawa H, Aoki M. Efficacy of Ramelteon for delirium after lung cancer surgery. Interact Cardiovasc Thorac Surg. 2017;24:8–12. Scholar
  38. 38.
    Morandi A, et al. The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*. Crit Care Med. 2012;40:2182–9. Scholar
  39. 39.
    Morita T, et al. Opioid rotation from morphine to fentanyl in delirious cancer patients: an open-label trial. J Pain Symptom Manage. 2005;30:96–103. Scholar
  40. 40.
    Moryl N, Kogan M, Comfort C, Obbens E. Methadone in the treatment of pain and terminal delirium in advanced cancer patients. Palliat Support Care. 2005; 3:311–7.CrossRefGoogle Scholar
  41. 41.
    Page VJ, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1:515–23.CrossRefGoogle Scholar
  42. 42.
    Pandharipande PP, Morandi A, Adams JR, Girard TD, Thompson JL, Shintani AK, Ely EW. Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients. Intensive Care Med. 2009;35:1886–92. Scholar
  43. 43.
    Pandharipande PP, 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. Scholar
  44. 44.
    Reade MC, et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315:1460–8. Scholar
  45. 45.
    Riker RR, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489–99. Scholar
  46. 46.
    Schaller SJ, et al. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet. 2016;388:1377–88. Scholar
  47. 47.
    Schreiber MP, et al. Corticosteroids and transition to delirium in patients with acute lung injury. Crit Care Med. 2014;42:1480–6. Scholar
  48. 48.
    Schweickert WD, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009;373:1874–82. Scholar
  49. 49.
    Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O’Neal PV, Keane KA, Tesoro EP, Elswick RK. The richmond agitation-sedation scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338–1344.CrossRefGoogle Scholar
  50. 50.
    Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. 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: 1075–84. Scholar
  51. 51.
    Shiiba M, Takei M, Nakatsuru M, Bukawa H, Yokoe H, Uzawa K, Tanzawa H. Clinical observations of postoperative delirium after surgery for oral carcinoma. Int J Oral Maxillofac Surg. 2009;38:661–5. Scholar
  52. 52.
    Siddiqi N, Harrison JK, Clegg A, Teale EA, Young J, Taylor J, Simpkins SA. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2016;3:CD005563. Scholar
  53. 53.
    Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med. 2004;30:444–9. Scholar
  54. 54.
    Sommer BR, Wise LC, Kraemer HC. Is dopamine administration possibly a risk factor for delirium? Crit Care Med. 2002;30:1508–11.CrossRefGoogle Scholar
  55. 55.
    Su X, et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016. Scholar
  56. 56.
    van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007;18: 1437–49. Scholar
  57. 57.
    van den Boogaard M, Schoonhoven L, van Achterberg T, van der Hoeven JG, Pickkers P. Haloperidol prophylaxis in critically ill patients with a high risk for delirium. Crit Care. 2013;17:R9. Scholar
  58. 58.
    van den Boogaard M, et al. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the REDUCE randomized clinical trial. JAMA. 2018;319:680–90. Scholar
  59. 59.
    van Eijk MM, 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;376:1829–37. Scholar
  60. 60.
    Vasunilashorn SM, et al. High C-reactive protein predicts delirium incidence, duration, and feature severity after major noncardiac surgery. J Am Geriatr Soc. 2017;65:e109–16. Scholar
  61. 61.
    Weinstein SM, et al. Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors. Br J Anaesth. 2018;120: 999–1008. Scholar
  62. 62.
    Winegarden J, Carr DB, Bradshaw YS. Intravenous ketamine for rapid opioid dose reduction, reversal of opioid-induced neurotoxicity, and pain control in terminal care: case report and literature review. Pain Med. 2016;17:644–9. Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Kimberly F. Rengel
    • 1
  • Daniel A. Nahrwold
    • 2
    • 3
  • Pratik P. Pandharipande
    • 4
  • Christopher G. Hughes
    • 1
    Email author
  1. 1.Department of Anesthesiology, Division of Anesthesiology Critical Care MedicineVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of AnesthesiologyMoffitt Cancer CenterTampaUSA
  3. 3.Department of Oncologic SciencesUniversity of South Florida, Morsani College of MedicineTampaUSA
  4. 4.Department of Anesthesiology and Surgery, Division of Anesthesiology Critical Care MedicineVanderbilt University Medical CenterNashvilleUSA

Section editors and affiliations

  • Yenny Cardenas
    • 1
  1. 1.Critical Care DepartmentUniversidad del Rosario Hospital Universitario Fundacion Santa Fe deBogotaColombia

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