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Pediatric Drugs
Published in: Pediatric Drugs 4/2014

01-08-2014 | Review Article

The Pharmacologic Management of Delirium in Children and Adolescents

Authors: Susan Beckwitt Turkel, Alan Hanft

Published in: Pediatric Drugs | Issue 4/2014

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Abstract

Delirium is a serious and common problem in severely medically ill patients of all ages. It has been less addressed in children and adolescents. Treatment of delirium is predicated on addressing its underlying cause. The management of its symptoms depends on the off-label use of antipsychotics, while avoiding agents that precipitate or worsen delirium. Olanzapine, quetiapine, and risperidone are presently considered first-line drugs, usually replacing haloperidol. Other agents have shown promise, including melatonin to address the sleep disturbance characteristic of delirium, and dexmedetomidine, an α2-agonist, that may facilitate lower doses of benzodiazepines and opioids that may worsen delirium.
Literature
1.
Engel GL, Romano J. Delirium, a syndrome of cerebral insufficiency. J Chronic Dis. 1959;9:260–77.PubMedCrossRef
2.
Romano J, Engel GL. Delirium I. Electroencephalographic data. Arch Neurol Psychiatr. 1944;51:356–77.CrossRef
3.
Breitbart W, Marotta R, Platt MM, Weisman H, Derevenco M, Grau C, Corbera K, Raymond S, Lund S, Jacobsen P. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatr. 1996;153:231–7.PubMed
4.
Trzepacz PT, Breitbart W, Levenson J, Franklin J, Martini DR. Practice guideline for the treatment of patients with delirium. Am J Psychiatr. 1999;156(5):1–20.
5.
Harrison AM, Lugo RA, Lee EW, Appachi E, Bourdakos D, Davis SJ, McHugh MJ, Weise KL. The use of haloperidol in agitated critically ill children. Clin Pediatr. 2002;41:51–4.CrossRef
6.
Deksnytė A, Aranauskas R, Budrys V, Kasieulevicė V, Ŝapoka V. Delirium: its historical evolution and current interpretation. Eur J Int Med. 2012;23:483–6.CrossRef
7.
Smeets IAP, Tan EYL, Vossen HGM, Leroy PLJM, Lousberg RHB, van Os J, Schieveld JNM. Prolonged stay at the pediatric intensive care unit associated with pediatric delirium. Eur Child Adolesc Psychiatr. 2010;19:389–93.CrossRef
8.
Eisendrath SJ, Shim JJ. Management of psychiatric problems in critically ill patients. Am J Med. 2006;119:22–9.PubMedCrossRef
9.
Lacasse H, Perreault MM, Williamson DR. Systemic review of antipsychotics for the treatment of hospital associated delirium in medically and surgically ill patients. Ann Pharmacother. 2006;40:1966–73.PubMedCrossRef
10.
Prugh DC, Wagonfield S, Metcalf D, Jordan K. A clinical study of delirium in children and adolescents. Psychosom Med. 1980;42 suppl:177–95.CrossRef
11.
Girard TD, Jackson JC, Pandharipande PP, Thompson JL, Shintani AK, Ely EW. Duration of delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Am J Respir Crit Care Med. 2009;179:A5477.
12.
Hatherill S, Flisher AJ. Delirium in children and adolescents: a systematic review of the literature. J Psychosom Res. 2010;68:337–44.PubMedCrossRef
13.
Rummans TA, Evans JM, Krahn LE, Fleming KC. Delirium in elderly patients: evaluation and management. Mayo Clin Proc. 1995;70:989–98.PubMedCrossRef
14.
de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. J Psychosom Res. 2007;62:521–5.PubMedCrossRef
15.
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.PubMedCrossRef
16.
Rudolph JL, Ramlawi B, Kuchel GA, McElhaney JE, Xie D, Sellke FW, Khabbaz K, Levkoff SE, Marcantonio ER. Chemokines are associated with delirium after cardiac surgery. J Gerontol A Biol Med Sci. 2008;63:184–9.
17.
Silver GH, Kearney JA, Kutko MC, Bartell AS. Infant delirium in pediatric critical care settings. Am J Psychiatr. 2010;167:1172–7.PubMedCrossRef
18.
19.
Cerejeira J, Nogueira V, Luis P, Vaz-Serra A, Mukaetova-Ladinska EB. The cholinergic system and inflammation: common pathways in delirium pathophysiology. J Am Geriatr Soc. 2012;60:669–75.PubMedCrossRef
20.
Eikelenboom P, Hoogendijk WJG, Jonker C, van Tilburg W. Immunologic mechanisms and the spectrum of psychiatric syndromes in Alzheimer’s disease. J Psychiatr Res. 2002;36:269–80.PubMedCrossRef
21.
Seaman JS, Schillerstrom J, Carroll D, Brown TM. Impaired oxidative metabolism precipitates delirium: a study of 101 ICU patients. Psychosomatics. 2006;47:56–61.PubMedCrossRef
22.
MacLullich AMJ, Ferguson KJ, Miller T, de Rooij SEJA, Cunningham C. Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress response. J Psychosom Res. 2008;65:229–38.PubMedCrossRef
23.
Tune L, Carr S, Hoag E, Cooper T. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatr. 1992;149:1393–4.PubMed
24.
25.
Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age Aging. 2011;40:23–9.CrossRef
26.
Stoddard FJ, Usher CT, Abrams AN. Psychopharmacology in pediatric critical care. Child Adolesc Clin North Am. 2006;15:611–55.CrossRef
27.
Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest. 1998;114:541–8.PubMedCrossRef
28.
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.PubMedCrossRef
29.
Schieveld JN, Staal M, Voogd L, Fioncken J, Vos G, van Os J. Refractory agitation as a marker for pediatric delirium in very young infants in the intensive care unit. Intensive Care Med. 2010;36:1982–3.PubMedCentralPubMedCrossRef
30.
Kean J, Trzepacz PT, Murray LL, Abell M, Trexler L. Initial validation of a brief provisional diagnostic scale for delirium. Brain Injury. 2010;24:1222–30.PubMedCrossRef
31.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, revised (DSM-TR-IV). Washington, DC: American Psychiatric Press; 2000.CrossRef
32.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Washington, DC: American Psychiatric Press; 2013.
33.
Turkel SB, Trzepacz PT, Tavare CJ. Comparing symptoms of delirium in adults and children. Psychosomatics. 2006;47:320–4.PubMedCrossRef
34.
Grover S, Kate N, Malhotra S, Chakrabarti S, Mattoo SK, Avasthi A. Symptom profile of delirium in children and adolescent—does it differ from adults and elderly? Gen Hosp Psychiatr. 2012;34:626–32.CrossRef
35.
Leentjens AFG, Schieveld JNM, Leonard M, Lousberg R, Verhey FRJ, Meagher DJ. A comparison of the phenomenology of pediatric, adult, and geriatric delirium. J Psychosom Res. 2008;64:219–23.PubMedCrossRef
36.
Turkel SB, Tavare CJ. Delirium in children and adolescents. J Neuropsychiatr Clin Neurosci. 2003;15:431–5.CrossRef
37.
Turkel SB, Jacobson J, Tavaré CJ. The diagnosis and management of delirium in infancy. J Child Adolesc Psychopharmacol. 2013;25:352–6.CrossRef
38.
Holditch-Davis D, Scher M, Schwartz T, Hudson-Barr D. Sleeping and waking state development in preterm infants. Early Hum Dev. 2004;80:43–64.PubMedCrossRef
39.
Meagher DJ, O’Hanlon D, O’Mahoney E, Casey PR, Trzepacz PT. Relationship between symptoms and motoric subtype of delirium.
40.
Hart RP, Levenson JL, Sessler CN, Best AM, Schwartz SM, Rutherford LE. Validation of a cognitive test for delirium in medical intensive care patients. Psychosomatics. 1996;37:533–46.PubMedCrossRef
41.
Grover S, Ghosh A, Kate N, Malhotra S, Mattoo SK, Chakrabarti S, Avasthi A. Do motor subtypes of delirium in child and adolescent have a different clinical and phenomenologic profile? Gen Hosp Psychiatry. 2014;36:187–91.PubMedCrossRef
42.
van der Mast RC. Pathophysiology of delirium. J Geriatr Psychiatr Neurol. 1998;11:138–45.CrossRef
43.
Grace JB, Holmes J. The management of behavioural and psychiatric symptoms in delirium. Expert Opin Pharmacother. 2006;7:555–61.PubMedCrossRef
44.
Meagher DJ, O’Hanlon D, O’Mahony E, Casey PR. The use of environmental strategies and psychotropic medication in the management of delirium. Br J Psychiatry. 1996;168:512–5.PubMedCrossRef
45.
Martini DR. Commentary: the diagnosis of delirium in pediatric patients. J Am Acad Child Adolesc Psychiatry. 2005;44:395–8.PubMedCrossRef
46.
Schieveld JN, Leeroy PL, van Os J, Nicolai J, Vos GD, Leentjens AP. Pediatric delirium in critical illness: phenomenology, clinical correlates and treatment response in 40 cases in the pediatric intensive care unit. Intensive Care Med. 2009;33:1033–40.CrossRef
47.
Bourne RS, Tahir TA, Borthwick M, Sampson EL. Drug treatment of delirium: past, present and future. J Psychosom Res. 2008;65:273–82.PubMedCrossRef
48.
Devlin JW, Al-Qadhee NS, Skrobik Y. Pharmacologic prevention and treatment of delirium in critically ill and non-critically ill hospitalized patients: a review of data from prospective, randomized studies. Best Pract Res Clin Anaesthesiol. 2012;26:289–309.PubMedCrossRef
49.
Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis, and treatment. Crit Care Clin. 2008;24:657–722.PubMedCrossRef
50.
DeMaso DR, Martini DR, Cahen LA, Bukstein O, Walter HJ, Benson S, Chrisman A, Farchione T, Hamilton J, Keable H, Kinlan J, Schoettle U, Siegel M, Stock S, Ptakowski KK, Medicus J, Work Group on Quality Issues. Practice parameter for the psychiatric assessment and management of physically ill children and adolescents. J Am Acad Child Adolesc Psychiatry. 2009;48:213–33.PubMedCrossRef
51.
Yoon H-J, Park K-M, Choi W-J, Choi S-H, Park J-Y, Kim J-J, Seok J-H. Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium. Br Med J Psychiatry. 2013;13:240–51.
52.
Smith HB, Fuchs DC, Pandharipande PP, Barr FE, Ely EW. Delirium: an emerging frontier in the management of critically ill children. Crit Care Clin. 2009;25:593–614.PubMedCentralPubMedCrossRef
53.
Smith HAB, Brink E, Fuchs DC, Ely EW, Pandharipande PP. Pediatric delirium: monitoring and management in the pediatric intensive care unit. Pediatr Clin North Am. 2013;60:741–60.PubMedCrossRef
54.
Turkel SB, Jacobson JR, Munzig E, Tavaré CJ. Atypical antipsychotic medications to control symptoms of delirium in children and adolescents. J Child Adolesc Psychopharmacol. 2012;22:126–30.PubMedCrossRef
55.
Maneeton B, Maneeton N, Srisurapanont M, Chittawatanarat K. Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial. Drug Design Dev Ther. 2013;7:657–67.CrossRef
56.
Tahir TA, Eeles E, Karapareddy V, Muthuvelu P, Chappie S, Phillips B, Adyemo T, Farewell D, Bisson JI. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. 2010;69:485–90.PubMedCrossRef
57.
Grover S, Kumar V, Chakrabarti S. Comparative efficacy study of haloperidol, olanzapine, and risperidone in delirium. J Psychosom Res. 2011;71:277–81.PubMedCrossRef
58.
Traube C, Witcher R, Mendez-Rico E, Silver G. Quetiapine as treatment for delirium in critically ill children: a case report. J Pediatr Intensive Care. 2013;2(3):121–6.
59.
60.
Sloof V. Adverse events of haloperidol for the treatment of delirium in critically ill children. Crit Care Med. 2012;40(12 Suppl):1–338.
61.
Boettger S, Breitbart W. Atypical antipsychotics in the management of delirium: a review of the empirical literature. Palliat Support Care. 2005;3:227–37.PubMedCrossRef
62.
Michaud L, Bula C, Berney A, Camus V, Voellinger R, Stiefel F, Burnand B, Delirium Guidelines Development Group. Delirium: guidelines for general hospitals. J Psychosom Res. 2007;62:371–83.PubMedCrossRef
63.
Alici-Evcimen Y, Breitbart W. An update on the use of antipsychotics in the treatment of delirium. Palliat Support Care. 2008;6:177–82.PubMedCrossRef
64.
Sonnier L, Barzman D. Pharmacologic management of acutely agitated pediatric patients. Pediatr Drugs. 2011;13(1):1–10.CrossRef
65.
66.
Sassano-Higgins S, Freudenberg N, Jacobson J, Turkel S. Olanzapine reduces delirium symptoms in the critically ill pediatric patient. J Pediatr Intensive Care. 2013;2:49–54.
67.
Ben-Amor L. Antipsychotics in pediatric and adolescent patients: a review of comparative safety data. J Affect Disord. 2012;138:S22–50.PubMedCrossRef
68.
Perrar KM, Golla H, Voltz R. Pharmacological treatment of delirium in palliative care patients. Der Schmerz. 2013;27:190–8.PubMedCrossRef
69.
Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials. Am J Psychiatry. 2014;171(2):151–9.PubMedCrossRef
70.
Seitz DP, Gill SS. Neuroleptic malignant syndrome complicating antipsychotic treatment of delirium or agitation in medical and surgical patients: case reports and a review of the literature. Psychosomatics. 2009;50:8–15.PubMedCrossRef
71.
Minns AB, Clark RF. Toxicology and overdose of atypical antipsychotics. J Emerg Med. 2012;43:906–13.PubMedCrossRef
72.
De Hert M, Detraux J, van Winkel R, Yu W, Correll CU. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nature Rev Endocrinol. 2012;8:114–26.CrossRef
73.
Correll CU, Kratochvil CJ. Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes. J Am Acad Child Adolesc Psychiatry. 2008;47(1):9–20.PubMedCrossRef
74.
75.
Leonard CE, Freeman CP, Newcomb CW, Bilker WB, Kimmel SE, Strom BL, Hennessy S. Antipsychotics and the risks of sudden cardiac death and all-cause death: cohort studies in Medicaid and dually-eligible Medicaid-Medicare beneficiaries of five states. J Clin Exp Cardiol. 2013;Suppl 10:1–9.
76.
Washington NB, Brahm NC, Kissack J. Which psychotropic carry the greatest risk of QTc prolongation? Curr Psychiatr. 2012;11:36–9.
77.
Gaertner I, Altendorf K, Batra A, Gaertner HJ. Relevance of liver enzyme elevations with four different neuroleptics: a retrospective review of 7263 treatment courses. J Clin Psychopharmacol. 2001;31:215–22.CrossRef
78.
Atasoy N, Erdogan A, Yalug I, Ozturk U, Konuk N, Atik L, Ustundag Y. A review of liver function tests during treatment with atypical antipsychotic drugs: a chart review study. Prog Neuro Psychopharm Biol Psychiatry. 2007;31:1255–60.CrossRef
79.
Szigethy E, Wiznitzer M, Branicky LA, Maxwell K, Findling RL. Ripseridone-induced hepatotoxicity in children and adolescents? A chart review study. J Child Adolesc Psychopharmacol. 1999;9:93–8.PubMedCrossRef
80.
Tabet N, Howard R. Pharmacological treatment for the prevention of delirium: review of current evidence. Int J Geriatr Psychiatry. 2009;24:1037–44.PubMedCrossRef
81.
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.PubMedCrossRef
82.
Bellaport J, Boots R. Potential use of melatonin in sleep and delirium in the critically ill. Br J Anaesth. 2012;108:572–80.CrossRef
83.
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.PubMedCrossRef
84.
Furuya M, Miyaoka T, Yasuda H, Yamashita S, Tanaka I, Otsuka S, Wake R, Horiguchi J. Marked improvement in delirium with ramelteon: five case reports. Psychogeriatrics. 2012;12:259–62.PubMedCrossRef
85.
Kain ZN, MacLaren JE, Herrmann L, Mayes L, Rosenbaum A, Hata J, Lerman J. Preoperative melatonin and its effects on induction and emergence in children undergoing anesthesia and surgery. Anesthesiology. 2009;111:44–9.PubMedCrossRef
86.
Hoy SM, Keating GM. Dexmedetomidine: a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. Drugs. 2011;71:1481–501.PubMedCrossRef
87.
Shukry M, Clyde MC, Kalarickal PI, Ramadhyani U. Does dexmedetomidine prevent emergency delirium in children after sevoflurane-based general anesthesia? Pediatr Anesth. 2005;15:1098–104.CrossRef
88.
Tobias JD, Gupta P, Naguib A. Dexmedetomidine: applications for the pediatric patient with congenital heart disease. Pediatr Cardiol. 2011;32:1075–87.PubMedCrossRef
89.
Buck ML, Willson DF. Use of dexmedetomidine in the pediatric intensive care unit. Pharmacotherapy. 2008;28(1):51–7.PubMedCrossRef
90.
Mason KP, Lerman J. Dexmedetomidine in children: current knowledge and future applications. Anesth Analg. 2011;113(5):1129–42.PubMedCrossRef
91.
Phan H, Nahata MC. Clinical uses of dexmedetomidine in pediatric patients. Pediatr Drugs. 2008;10(1):49–69.CrossRef
92.
Honey BL, Benefield RJ, Miller JL, Johnson PN. α2-Receptor agonists for treatment and prevention of iatrogenic opioid abstinence syndrome in critically ill patients. Ann Pharmacother. 2009;43:1056–511.CrossRef
93.
Riker RR, Fraser GL. Adverse events associated with sedatives, analgesics, and other drugs that provide patient comfort in the intensive care unit. Pharmacotherapy. 2005;25(pt 2):8S–18S.PubMedCrossRef
94.
Resnick M, Burton BT. Droperidol vs haloperidol in the initial management of acutely agitated patients. J Clin Psychiatry. 1984;45:298–9.PubMed
95.
Bourcher BA. Formulary decisions: then and now. Pharmacotherapy. 2010;6(Pt 2):35S–41S.CrossRef
96.
Bostwick JM, Masterson BJ. Psychopharmacological treatment of delirium to restore mental capacity. Psychosomatics. 1998;39:112–7.PubMedCrossRef
97.
Shaw GK. Detoxification: the use of benzodiazepines. Alcohol Alcohol. 1995;30:765–70.PubMed
98.
Leggio L, Kenna GA, Swift RM. New developments for the pharmacological treatment of alcohol withdrawal syndrome: a focus on non-benzodiazepine GABA-ergic medications. Prog Neuro Psychopharmacol Biol Psychiatry. 2008;32:1106–17.CrossRef
99.
Shaner R. Benzodiazepines in psychiatric emergency settings. Psychiatr Ann. 2000;30:268–75.CrossRef
100.
Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006;104:21–6.PubMedCrossRef
101.
Caccia S. Safety and pharmacokinetics of atypical antipsychotics in children and adolescents. Paediatr Drugs. 2013;15:217–33.PubMedCrossRef
102.
Lawrence KR, Nasraway SA. Conduction disturbances associated with administration of butyrophenone antipsychotics in the critically ill: a review of the literature. Pharmacotherapy. 1997;17(3):531–7.PubMed
Metadata
Title
The Pharmacologic Management of Delirium in Children and Adolescents
Authors
Susan Beckwitt Turkel
Alan Hanft
Publication date
01-08-2014
Publisher
Springer International Publishing
Published in
Pediatric Drugs / Issue 4/2014
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI
https://doi.org/10.1007/s40272-014-0078-0

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