Delirium in the Pediatric Critical Care Oncologic Patient

  • Sydney Nicole AriagnoEmail author
  • Chani Traube
Reference work entry


Delirium is an acute and fluctuating change in cognition and attention that arises as a result of underlying physical illness. In critically ill children, delirium is a prevalent, yet underrecognized complication of hospitalization. Pediatric oncologic patients are at particularly high risk of developing delirium. This condition arises as a result of three intersecting triggers: the patient’s primary medical illness, the side effects of treatment(s) for that illness, and the highly abnormal environment of the intensive care unit. A number of intrinsic and modifiable risk factors for delirium are known, allowing medical teams to identify patients who are most susceptible. Three clinical subtypes of delirium have been described – hyperactive, hypoactive, and mixed – with the hypoactive being the most common and also the most dangerous. Pediatric delirium may be diagnosed by psychiatric evaluation or by a validated screening tool. Attention to preventing, diagnosing, and treating delirium is imperative, as delirium is associated with a number of negative sequelae including increased length of hospitalization, psycho-emotional stress, and mortality. However, with prompt treatment, the vast majority of delirium cases are reversible.


Delirium Pediatric Cancer Hematology Oncology Critical care ICU 


  1. 1.
    Aliev G, Obrenovich ME, Smith MA, Perry G. Hypoperfusion, mitochondria failure, oxidative stress, and Alzheimer disease. J Biomed Biotechnol. 2003;2003:162–3. Scholar
  2. 2.
    Alvarez RV, Palmer C, Czaja AS, et al. Delirium is a common and early finding in patients in the pediatric cardiac intensive care unit. J Pediatr. 2018;195:206–12. Scholar
  3. 3.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. Arlington: American Psychiatric Association; 2013.CrossRefGoogle Scholar
  4. 4.
    Aydogan MS, Korkmaz MF, Ozgül U, et al. Pain, fentanyl consumption, and delirium in adolescents after scoliosis surgery: dexmedetomidine vs midazolam. Pediatr Anesth. 2013;23:446–52. Scholar
  5. 5.
    Banh HL. Management of delirium in adult critically ill patients: an overview. J Pharm Pharm Sci. 2012;15:499. Scholar
  6. 6.
    Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263–306. Scholar
  7. 7.
    Basinski JR, Alfano CM, Katon WJ, et al. Impact of delirium on distress, health-related quality of life, and cognition 6 months and 1 year after hematopoietic cell transplant. Biol Blood Marrow Transplant. 2010;16:824–31. Scholar
  8. 8.
    Breitbart W, Gibson C, Tremblay A. The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics. 2002;43:183–94. Scholar
  9. 9.
    Breitbart W, Alici Y. Agitation and delirium at the end of life. JAMA. 2008;300:2898. Scholar
  10. 10.
    Breitbart W, Alici Y. Evidence-based treatment of delirium in patients with cancer. J Clin Oncol. 2012;30:1206–14. Scholar
  11. 11.
    Caraceni A, Nanni O, Maltoni M, et al. Impact of delirium on the short term prognosis of advanced cancer patients. Cancer. 2000;89:1145–9.<1145::aid-cncr24>;2-x.CrossRefPubMedGoogle Scholar
  12. 12.
    Carrasco G, Baeza N, Cabré L, et al. Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in nonintubated ICU patients. Crit Care Med. 2016;44:1295–306. Scholar
  13. 13.
    Cerejeira J, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB. The neuroinflammatory hypothesis of delirium. Acta Neuropathol. 2010;119:737–54. Scholar
  14. 14.
    Colville G, Tighe H, Pierce C. Childrenʼs factual and delusional memories of paediatric intensive care. Crit Care Med. 2008.
  15. 15.
    Combs D, Rice SA, Kopp LM. Incidence of delirium in children with cancer. Pediatr Blood Cancer. 2014;61:2094–5. Scholar
  16. 16.
    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
  17. 17.
    Engel GL, Romano J. Delirium, a syndrome of cerebral insufficiency. J Neuropsychiatr. 1959;16:526–38. Scholar
  18. 18.
    Fann JR, Roth-Roemer S, Burington BE, et al. Delirium in patients undergoing hematopoietic stem cell transplantation. Cancer. 2002;95:1971–81. Scholar
  19. 19.
    Fann JR, Alfano CM, Burington BE, et al. Clinical presentation of delirium in patients undergoing hematopoietic stem cell transplantation. Cancer. 2005;103:810–20. Scholar
  20. 20.
    Fann JR, Alfano CM, Roth-Roemer S, et al. Impact of delirium on cognition, distress, and health-related quality of life after hematopoietic stem-cell transplantation. J Clin Oncol. 2007;25:1223–31. Scholar
  21. 21.
    Flacker JM, Cummings V, Mach JR, et al. The association of serum anticholinergic activity with delirium in elderly medical patients. Am J Geriatr Psychiatr. 1998;6:31–41. Scholar
  22. 22.
    Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol Ser A Biol Med Sci. 1999.
  23. 23.
    Golinger RC, Peet T, Tune LE. Association of elevated plasma anticholinergic activity with delirium in surgical patients. Am J Psychiatr. 1987;144:1218–20. Scholar
  24. 24.
    Grandahl MG, Nielsen SE, Koerner EA, et al. Prevalence of delirium among patients at a cancer ward: clinical risk factors and prediction by bedside cognitive tests. Nord J Psychiatry. 2016;70:413–7. Scholar
  25. 25.
    Grover S, Kate N, Malhotra S, et al. Symptom profile of delirium in children and adolescent—does it differ from adults and elderly? Gen Hosp Psychiatry. 2012;34:626–32. Scholar
  26. 26.
    Harris J, Ramelet A-S, Dijk MV, et al. Clinical recommendations for pain, sedation, withdrawal and delirium assessment in critically ill infants and children: an ESPNIC position statement for healthcare professionals. Intensive Care Med. 2016;42:972–86. Scholar
  27. 27.
    Hipp DM, Ely EW. Pharmacological and nonpharmacological management of delirium in critically ill patients. Neurotherapeutics. 2012;9:158–75. Scholar
  28. 28.
    Jonghe AD, Munster BCV, Oosten HEV, et al. The effects of melatonin versus placebo on delirium in hip fracture patients: study protocol of a randomized, placebo-controlled, double blind trial. BMC Geriatr. 2011.
  29. 29.
    Joyce C, Witcher R, Herrup E, et al. Evaluation of the safety of quetiapine in treating delirium in critically ill children: a retrospective review. J Child Adolesc Psychopharmacol. 2015;25:666–70. Scholar
  30. 30.
    Karnik NS, Joshi SV, Paterno C, Shaw R. Subtypes of pediatric delirium: a treatment algorithm. Psychosomatics. 2007;48:253–7. Scholar
  31. 31.
    Kudchadkar SR, Yaster M, Punjabi NM. Sedation, sleep promotion, and delirium screening practices in the care of mechanically ventilated children. Crit Care Med. 2014;42:1592–600. Scholar
  32. 32.
    Kwok T, Lee J, Lam L, et al. Vitamin B12 supplementation did not improve cognition but reduced delirium in demented patients with vitamin B12 deficiency. Arch Gerontol Geriatr. 2008;46:273–82. Scholar
  33. 33.
    Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer. Arch Intern Med. 2000;160:786. Scholar
  34. 34.
    Lawlor PG, Bruera ED. Delirium in patients with advanced cancer. Hematol Oncol Clin N Am. 2002;16:701–14. Scholar
  35. 35.
    Lipowski ZJ. Delirium (acute confusional states). JAMA J Am Med Assoc. 1987;258:1789. Scholar
  36. 36.
    Maldonado JR. Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment. Crit Care Clin. 2008;24:789–856. Scholar
  37. 37.
    Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21:1190–222. Scholar
  38. 38.
    Malviya S, Voepel-Lewis T, Ramamurthi RJ, et al. Clonidine for the prevention of emergence agitation in young children: efficacy and recovery profile. Pediatr Anesth. 2006;16:554–9. Scholar
  39. 39.
    Matsuoka H, Yoshiuchi K, Koyama A, et al. Chemotherapeutic drugs that penetrate the blood–brain barrier affect the development of hyperactive delirium in cancer patients. Palliat Support Care. 2014;13:859–64. Scholar
  40. 40.
    Mcpherson JA, Wagner CE, Boehm LM, et al. Delirium in the cardiovascular ICU. Crit Care Med. 2013;41:405–13. Scholar
  41. 41.
    Meagher DJ, Ohanlon D, Omahony E, et al. Relationship between symptoms and motoric subtype of delirium. J Neuropsychiatry Clin Neurosci. 2000;12:51–6. Scholar
  42. 42.
    Meyburg J, Dill M-L, Traube C, et al. Patterns of postoperative delirium in children*. Pediatr Crit Care Med. 2017;18:128–33. Scholar
  43. 43.
    Miyazaki T, Kuwano H, Kato H, et al. Correlation between serum melatonin circadian rhythm and intensive care unit psychosis after thoracic esophagectomy. Surgery. 2003;133:662–8. Scholar
  44. 44.
    Modi K, Kaur S, Mauer EA, et al. Benzodiazepines and development of delirium in critically ill children. Crit Care Med. 2018;46:1486–91. Scholar
  45. 45.
    Needham DM, Korupolu R, Zanni JM, et al. Early physical medicine and rehabilitation for patients with acute respiratory failure: a quality improvement project. Arch Phys Med Rehabil. 2010;91:536–42. Scholar
  46. 46.
    O’Keeffe S, Devlin J. Delirium and the dexamethasone suppression test in the elderly. Neuropsychobiology. 1994;30:153–6. Scholar
  47. 47.
    O’Keeffe S, Tormey W, Glasgow R, et al. Thiamine deficiency in hospitalized elderly patients. Gerontology. 1994;40:18–24. Scholar
  48. 48.
    Olofsson K, Alling C, Lundberg D, Malmros C. Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients. Acta Anaesthesiol Scand. 2004;48:679–84. Scholar
  49. 49.
    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.
  50. 50.
    Patel AK, Biagas KV, Clarke EC, et al. Delirium in children after cardiac bypass surgery*. Pediatr Crit Care Med. 2017a;18:165–71. Scholar
  51. 51.
    Patel AK, Bell MJ, Traube C. Delirium in pediatric critical care. Pediatr Clin N Am. 2017b;64:1117–32. Scholar
  52. 52.
    Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci. 1999;22:273–80. Scholar
  53. 53.
    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;54:479–84. Scholar
  54. 54.
    Pisani MA, Kong SYJ, Kasl SV, et al. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009;180:1092–7. Scholar
  55. 55.
    Posner MI, Rothbart MK, Sheese BE, Voelker P. Control networks and neuromodulators of early development. Dev Psychol. 2012;48:827–35. Scholar
  56. 56.
    Scarpi E, Maltoni M, Nanni O, et al. Survival prediction for terminally ill patients with cancer: revision of palliative prognostic score with incorporation of delirium. Oncologist. 2011.
  57. 57.
    Schieveld JNM, Leroy PLJM, Os JV, et al. Pediatric delirium in critical illness: phenomenology, clinical correlates and treatment response in 40 cases in the pediatric intensive care unit. Intensive Care Med. 2007;33:1033–40. Scholar
  58. 58.
    Schieveld JNM, Tuijl SV, Pikhard T. On nontraumatic brain injury in pediatric critical illness, neuropsychologic short-term outcome, delirium, and resilience*. Crit Care Med. 2013;41:1160–1. Scholar
  59. 59.
    Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomized controlled trial. Lancet. 2009;373:1874–82. Scholar
  60. 60.
    Şenel G, Uysal N, Oguz G, et al. Delirium frequency and risk factors among patients with cancer in palliative care unit. Am J Hosp Palliat Med®. 2016;34:282–6. Scholar
  61. 61.
    Shehabi Y, Riker RR, Bokesch PM, et al. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients*. Crit Care Med. 2010;38:2311–8. Scholar
  62. 62.
    Sher Y, Cramer ACM, Ament A, et al. Valproic acid for treatment of hyperactive or mixed delirium: rationale and literature review. Psychosomatics. 2015;56:615–25. Scholar
  63. 63.
    Silver G, Traube C, Kearney J, et al. Detecting pediatric delirium: development of a rapid observational assessment tool. Intensive Care Med. 2012;38:1025–31. Scholar
  64. 64.
    Silver G, Kearney J, Traube C, et al. Pediatric delirium: evaluating the gold standard. Palliat Support Care. 2014;13:513–6. Scholar
  65. 65.
    Silver G, Traube C, Gerber LM, et al. Pediatric delirium and associated risk factors. Pediatr Crit Care Med. 2015a;16:303–9. Scholar
  66. 66.
    Silver G, Kearney J, Traube C, Hertzig M. Delirium screening anchored in child development: the Cornell Assessment for Pediatric Delirium. Palliat Support Care. 2015b;13:1005–11. Scholar
  67. 67.
    Simone S, Edwards S, Lardieri A, et al. Implementation of an ICU bundle. Pediatr Crit Care Med. 2017;18:531–40. Scholar
  68. 68.
    Smith HAB, 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*. Crit Care Med. 2011;39:150–7. Scholar
  69. 69.
    Smith HAB, Brink E, Fuchs DC, Ely EW, Pandharipande PP. Pediatric delirium: monitoring and management in the pediatric intensive care unit. Crit Care Pediatr Patient. 2013;60:741–60. Scholar
  70. 70.
    Smith HAB, Gangopadhyay M, Goben CM, et al. The preschool confusion assessment method for the ICU. Crit Care Med. 2015;44:592–600. Scholar
  71. 71.
    Smith HAB, Gangopadhyay M, Goben CM, et al. Delirium and benzodiazepines associated with prolonged ICU stay in critically ill infants and young children*. Crit Care Med. 2017;45:1427–35. Scholar
  72. 72.
    Sultan S. Assessment of role of perioperative melatonin in prevention and treatment of postoperative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth. 2010;4:169. Scholar
  73. 73.
    Tobias JD. Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit. Crit Care Med. 2000;28:2122–32. Scholar
  74. 74.
    Tobias JD. Acute pain management in infants and children—part 1: pain pathways, pain assessment, and outpatient pain management. Pediatr Ann. 2014a.
  75. 75.
    Tobias JD. Acute pain management in infants and children—part 2: intravenous opioids, intravenous nonsteroidal anti-inflammatory drugs, and managing adverse effects. Pediatr Ann. 2014b.
  76. 76.
    Traube C, Witcher R, Mendez-Rico E, Silver G. Quetiapine as treatment for delirium in critically ill children: a case series. J Pediatr Intensive Care. 2013;2:121–6. Scholar
  77. 77.
    Traube C, Silver G, Kearney J, et al. Cornell Assessment of Pediatric Delirium: a valid, rapid, observational tool for screening delirium in the PICU. Crit Care Med. 2014;42:656–63. Scholar
  78. 78.
    Traube C, Mauer EA, Gerber LM, et al. Cost associated with pediatric delirium in the ICU. Crit Care Med. 2016.
  79. 79.
    Traube C, Silver G, Reeder RW, et al. Delirium in critically ill children: an international point prevalence study. Crit Care Med. 2017a;45:584–90. Scholar
  80. 80.
    Traube C, Silver G, Gerber LM, et al. Delirium and mortality in critically ill children. Crit Care Med. 2017b;45:891–8. Scholar
  81. 81.
    Traube C, Ariagno S, Thau F, et al. Delirium in hospitalized children with cancer: incidence and associated risk factors. J Pediatr. 2017c;191:212–7. Scholar
  82. 82.
    Trzepacz PT. Update on the neuropathogenesis of delirium. Dement Geriatr Cogn Disord. 1999;10:330–4. Scholar
  83. 83.
    Turkel SB, Jacobson J, Munzig E, Tavaré CJ. Atypical antipsychotic medications to control symptoms of delirium in children and adolescents. J Child Adolesc Psychopharmacol. 2012;22:126–30. Scholar
  84. 84.
    Tune LE. Serum anticholinergic activity levels and delirium in the elderly. Semin Clin Neuropsychiatry. 2000;5:149–53.
  85. 85.
    van Hemert A, van der Mast RC, Hengeveid MW, Vorstenbosch M. Excess mortality in general hospital patients with delirium. J Psychosom Res. 1994;38:339–46. Scholar
  86. 86.
    Turkel SB, Trzepacz PT, Tavare J. Comparing symptoms of delirium in adults and children. Psychosomatics. 2006. 47:320–4.

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Weill Cornell MedicineNew YorkUSA
  2. 2.Department of Pediatrics, Division of Pediatric Critical Care MedicineWeill Cornell MedicineNew YorkUSA

Section editors and affiliations

  • Rodrigo Mejia
    • 1
  1. 1.Pediatric Critical CareMD Anderson Cancer CenterHoustonUSA

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