J Pediatr Intensive Care 2023; 12(02): 094-105
DOI: 10.1055/s-0041-1730918
Review Article

Assessment and Management of Delirium in the Pediatric Intensive Care Unit: A Review

1   Department of Pharmacy, St. Louis Children's Hospital, St. Louis, Missouri, United States
,
Christopher McPherson
1   Department of Pharmacy, St. Louis Children's Hospital, St. Louis, Missouri, United States
2   Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States
,
Caitlyn Luecke
1   Department of Pharmacy, St. Louis Children's Hospital, St. Louis, Missouri, United States
› Institutsangaben

Abstract

Many critically ill patients suffer from delirium which is associated with significant morbidity and mortality. There is a paucity of data about the incidence, symptoms, or treatment of delirium in the pediatric intensive care unit (PICU). Risk factors for delirium are common in the PICU including central nervous system immaturity, developmental delay, mechanical ventilation, and use of anticholinergic agents, corticosteroids, vasopressors, opioids, or benzodiazepines. Hypoactive delirium is the most common subtype in pediatric patients; however, hyperactive delirium has also been reported. Various screening tools are validated in the pediatric population, with the Cornell Assessment of Pediatric Delirium (CAPD) applicable to the largest age range and able to detect signs and symptoms consistent with both hypo- and hyperactive delirium. Treatment of delirium should always include identification and reversal of the underlying etiology, reserving pharmacologic management for those patients without symptom resolution, or with significant impact to medical care. Atypical antipsychotics (olanzapine, quetiapine, and risperidone) should be used first-line in patients requiring pharmacologic treatment owing to their apparent efficacy and low incidence of reported adverse effects. The choice of atypical antipsychotic should be based on adverse effect profile, available dosage forms, and consideration of medication interactions. Intravenous haloperidol may be a potential treatment option in patients unable to tolerate oral medications and with significant symptoms. However, given the high incidence of serious adverse effects with intravenous haloperidol, routine use should be avoided. Dexmedetomidine should be used when sedation is needed and when clinically appropriate, given the positive impact on delirium. Additional well-designed trials assessing screening and treatment of PICU delirium are needed.



Publikationsverlauf

Eingereicht: 02. März 2021

Angenommen: 31. März 2021

Artikel online veröffentlicht:
08. Juni 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.. Arlington, VA: CBS; 2013
  • 2 Turkel SB. Pediatric delirium: recognition, management, and outcome. Curr Psychiatry Rep 2017; 19 (12) 101
  • 3 Slooter AJ, Van De Leur RR, Zaal IJ. Delirium in critically ill patients. Handb Clin Neurol 2017; 141: 449-466
  • 4 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 (07) 1513-1520
  • 5 Devlin JW, Skrobik Y, Gélinas C. 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 (09) e825-e873
  • 6 Smith HA, 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 (01) 150-157
  • 7 Smith HA, Gangopadhyay M, Goben CM. et al. The preschool confusion assessment method for the ICU: valid and reliable delirium monitoring for critically ill infants and children. Crit Care Med 2016; 44 (03) 592-600
  • 8 Turkel SB, Jacobson JR, Tavaré CJ. The diagnosis and management of delirium in infancy. J Child Adolesc Psychopharmacol 2013; 23 (05) 352-356
  • 9 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 (03) 656-663
  • 10 Traube C, Mauer EA, Gerber LM. et al. Cost associated with pediatric delirium in the ICU. Crit Care Med 2016; 44 (12) e1175-e1179
  • 11 Silver G, Traube C, Gerber LM. et al. Pediatric delirium and associated risk factors: a single-center prospective observational study. Pediatr Crit Care Med 2015; 16 (04) 303-309
  • 12 Traube C, Silver G, Gerber LM. et al. Delirium and mortality in critically ill children: epidemiology and outcomes of pediatric delirium. Crit Care Med 2017; 45 (05) 891-898
  • 13 Janssen NJ, Tan EY, Staal M. et al. On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the Pediatric Anesthesia Emergence Delirium Scale, the Delirium Rating Scale 88, and the Delirium Rating Scale-Revised R-98. Intensive Care Med 2011; 37 (08) 1331-1337
  • 14 Luetz A, Gensel D, Müller J. et al. Validity of different delirium assessment tools for critically ill children: covariates matter. Crit Care Med 2016; 44 (11) 2060-2069
  • 15 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 (14) 1753-1762
  • 16 Brahmbhatt K, Whitgob E. Diagnosis and management of delirium in critically ill infants: case report and review. Pediatrics 2016; 137 (03) e20151940
  • 17 Patel AK, Bell MJ, Traube C. Delirium in pediatric critical care. Pediatr Clin North Am 2017; 64 (05) 1117-1132
  • 18 Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry 2013; 21 (12) 1190-1222
  • 19 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 (04) 789-856 , ix ix
  • 20 Cerejeira J, Nogueira V, Luís P, Vaz-Serra A, Mukaetova-Ladinska EB. The cholinergic system and inflammation: common pathways in delirium pathophysiology. J Am Geriatr Soc 2012; 60 (04) 669-675
  • 21 de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. J Psychosom Res 2007; 62 (05) 521-525
  • 22 Schoen J, Meyerrose J, Paarmann H, Heringlake M, Hueppe M, Berger KU. Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: a prospective observational trial. Crit Care 2011; 15 (05) R218
  • 23 Seaman JS, Schillerstrom J, Carroll D, Brown TM. Impaired oxidative metabolism precipitates delirium: a study of 101 ICU patients. Psychosomatics 2006; 47 (01) 56-61
  • 24 Potts MB, Koh SE, Whetstone WD. et al. Traumatic injury to the immature brain: inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets. NeuroRx 2006; 3 (02) 143-153
  • 25 Bayir H, Kagan VE, Tyurina YY. et al. Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Res 2002; 51 (05) 571-578
  • 26 Madden K, Hussain K, Tasker RC. Anticholinergic medication burden in pediatric prolonged critical illness: a potentially modifiable risk factor for delirium. Pediatr Crit Care Med 2018; 19 (10) 917-924
  • 27 Mody K, Kaur S, Mauer EA. et al. Benzodiazepines and development of delirium in critically ill children: estimating the causal effect. Crit Care Med 2018; 46 (09) 1486-1491
  • 28 Hatherill S, Flisher AJ. Delirium in children and adolescents: a systematic review of the literature. J Psychosom Res 2010; 68 (04) 337-344
  • 29 Schieveld JN, Leroy PL, van Os J, Nicolai J, Vos GD, Leentjens AF. 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 (06) 1033-1040
  • 30 Turkel SB, Tavaré CJ. Delirium in children and adolescents. J Neuropsychiatry Clin Neurosci 2003; 15 (04) 431-435
  • 31 Ista E, van Beusekom B, van Rosmalen J. et al. Validation of the SOS-PD scale for assessment of pediatric delirium: a multicenter study. Crit Care 2018; 22 (01) 309
  • 32 Harris J, Ramelet AS, van Dijk M. 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 (06) 972-986
  • 33 Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology 2004; 100 (05) 1138-1145
  • 34 Turkel SB, Braslow K, Tavaré CJ, Trzepacz PT. The delirium rating scale in children and adolescents. Psychosomatics 2003; 44 (02) 126-129
  • 35 Silver G, Traube C, Kearney J. et al. Detecting pediatric delirium: development of a rapid observational assessment tool. Intensive Care Med 2012; 38 (06) 1025-1031
  • 36 Schieveld JN. On pediatric delirium and the use of the pediatric confusion assessment method for the intensive care unit. Crit Care Med 2011; 39 (01) 220-221
  • 37 Kaur S, Silver G, Samuels S. et al. Delirium and developmental disability: improving specificity of a pediatric delirium screen. Pediatr Crit Care Med 2020; 21 (05) 409-414
  • 38 Ista E, Te Beest H, van Rosmalen J. et al. Sophia observation withdrawal symptoms-paediatric delirium scale: a tool for early screening of delirium in the PICU. Aust Crit Care 2018; 31 (05) 266-273
  • 39 Malas N, Brahmbhatt K, McDermott C, Smith A, Ortiz-Aguayo R, Turkel S. Pediatric delirium: evaluation, management, and special considerations. Curr Psychiatry Rep 2017; 19 (09) 65
  • 40 Kudchadkar SR, Yaster M, Punjabi NM. Sedation, sleep promotion, and delirium screening practices in the care of mechanically ventilated children: a wake-up call for the pediatric critical care community. Crit Care Med 2014; 42 (07) 1592-1600
  • 41 Kudchadkar SR, Aljohani OA, Punjabi NM. Sleep of critically ill children in the pediatric intensive care unit: a systematic review. Sleep Med Rev 2014; 18 (02) 103-110
  • 42 Turkel SB, Hanft A. The pharmacologic management of delirium in children and adolescents. Paediatr Drugs 2014; 16 (04) 267-274
  • 43 Mauri MC, Paletta S, Maffini M. et al. Clinical pharmacology of atypical antipsychotics: an update. EXCLI J 2014; 13: 1163-1191
  • 44 Silver GH, Kearney JA, Kutko MC, Bartell AS. Infant delirium in pediatric critical care settings. Am J Psychiatry 2010; 167 (10) 1172-1177
  • 45 Kuepper R, Skinbjerg M, Abi-Dargham A. The dopamine dysfunction in schizophrenia revisited: new insights into topography and course. Handb Exp Pharmacol 2012; (212) 1-26
  • 46 Lacasse H, Perreault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients. Ann Pharmacother 2006; 40 (11) 1966-1973
  • 47 Saeedi H, Remington G, Christensen BK. Impact of haloperidol, a dopamine D2 antagonist, on cognition and mood. Schizophr Res 2006; 85 (1–3): 222-231
  • 48 Aronow WS, Shamliyan TA. Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders. Ann Transl Med 2018; 6 (08) 147
  • 49 Richelson E. Receptor pharmacology of neuroleptics: relation to clinical effects. J Clin Psychiatry 1999; 60 (Suppl. 10) 5-14
  • 50 Kusumi I, Boku S, Takahashi Y. Psychopharmacology of atypical antipsychotic drugs: From the receptor binding profile to neuroprotection and neurogenesis. Psychiatry Clin Neurosci 2015; 69 (05) 243-258
  • 51 Dremencov E, Weizmann Y, Kinor N, Gispan-Herman I, Yadid G. Modulation of dopamine transmission by 5HT2C and 5HT3 receptors: a role in the antidepressant response. Curr Drug Targets 2006; 7 (02) 165-175
  • 52 Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 2008; 13 (01) 27-35
  • 53 Turkel S, Hanft A, Epstein D, Jacobson J. Review of delirium in the pediatric intensive care unit. J Pediatr Intensive Care 2013; 2 (04) 169-176
  • 54 Siafis S, Tzachanis D, Samara M, Papazisis G. Antipsychotic drugs: from receptor-binding profiles to metabolic side effects. Curr Neuropharmacol 2018; 16 (08) 1210-1223
  • 55 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 2010; 38 (02) 419-427
  • 56 Girard TD, Pandharipande PP, Carson SS. et al; MIND Trial Investigators. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 2010; 38 (02) 428-437
  • 57 Girard TD, Exline MC, Carson SS. et al; MIND-USA Investigators. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med 2018; 379 (26) 2506-2516
  • 58 Page VJ, Ely EW, Gates S. 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 (07) 515-523
  • 59 Burry L, Hutton B, Williamson DR. et al. Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev 2019; 9: CD011749
  • 60 Ben Amor L. Antipsychotics in pediatric and adolescent patients: a review of comparative safety data. J Affect Disord 2012; 138 (suppl): S22-S30
  • 61 Kishk OA, Simone S, Lardieri AB, Graciano AL, Tumulty J, Edwards S. Antipsychotic treatment of delirium in critically ill children: a retrospective matched cohort study. J Pediatr Pharmacol Ther 2019; 24 (03) 204-213
  • 62 Brown RL, Henke A, Greenhalgh DG, Warden GD. The use of haloperidol in the agitated, critically ill pediatric patient with burns. J Burn Care Rehabil 1996; 17 (01) 34-38
  • 63 Ratcliff SL, Meyer III WJ, Cuervo LJ, Villarreal C, Thomas CR, Herndon DN. The use of haloperidol and associated complications in the agitated, acutely ill pediatric burn patient. J Burn Care Rehabil 2004; 25 (06) 472-478
  • 64 Slooff VD, van den Dungen DK, van Beusekom BS. et al. Monitoring haloperidol plasma concentration and associated adverse events in critically ill children with delirium: first results of a clinical protocol aimed to monitor efficacy and safety. Pediatr Crit Care Med 2018; 19 (02) e112-e119
  • 65 Harrison AM, Lugo RA, Lee WE. et al. The use of haloperidol in agitated critically ill children. Clin Pediatr (Phila) 2002; 41 (01) 51-54
  • 66 Schieveld JN, Leentjens AF. Delirium in severely ill young children in the pediatric intensive care unit (PICU). J Am Acad Child Adolesc Psychiatry 2005; 44 (04) 392-394 , discussion 395
  • 67 Carlton EF, Mahowald MK, Malas N. Management of multifactorial infant delirium with intravenous haloperidol in the setting of over sedation and poor enteral absorption. J Child Adolesc Psychopharmacol 2017; 27 (03) 289-290
  • 68 Capino AC, Thomas AN, Baylor S, Hughes KM, Miller JL, Johnson PN. Antipsychotic use in the prevention and treatment of intensive care unit delirium in pediatric patients. J Pediatr Pharmacol Ther 2020; 25 (02) 81-95
  • 69 Madden K, Turkel S, Jacobson J, Epstein D, Moromisato DY. Recurrent delirium after surgery for congenital heart disease in an infant. Pediatr Crit Care Med 2011; 12 (06) e413-e415
  • 70 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 (02) 49-54
  • 71 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 (02) 126-130
  • 72 Groves A, Traube C, Silver G. Detection and management of delirium in the neonatal unit: a case series. Pediatrics 2016; 137 (03) e20153369
  • 73 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 (03) 121-126
  • 74 Traube C, Augenstein J, Greenwald B, LaQuaglia M, Silver G. Neuroblastoma and pediatric delirium: a case series. Pediatr Blood Cancer 2014; 61 (06) 1121-1123
  • 75 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 (09) 666-670
  • 76 Spina E, Hiemke C, de Leon J. Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics. Expert Opin Drug Metab Toxicol 2016; 12 (04) 407-422
  • 77 Campbell CT, Grey E, Munoz-Pareja J, Manasco KB. An evaluation of risperidone dosing for pediatric delirium in children less than or equal to 2 years of age. Ann Pharmacother 2020; 54 (05) 464-469
  • 78 Edwards LE, Hutchison LB, Hornik CD, Smith PB, Cotten CM, Bidegain M. A case of infant delirium in the neonatal intensive care unit. J Neonatal Perinatal Med 2017; 10 (01) 119-123
  • 79 Karnik NS, Joshi SV, Paterno C, Shaw R. Subtypes of pediatric delirium: a treatment algorithm. Psychosomatics 2007; 48 (03) 253-257
  • 80 Hutchins LM, Shipman A, Zimmerman KO, Heath TS. Evaluation of QTc interval effects of antipsychotic medications for intensive care unit delirium in pediatric patients. J Pediatr Pharmacol Ther 2021; 26 (01) 87-91
  • 81 Cerovecki A, Musil R, Klimke A. et al. Withdrawal symptoms and rebound syndromes associated with switching and discontinuing atypical antipsychotics: theoretical background and practical recommendations. CNS Drugs 2013; 27 (07) 545-572
  • 82 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 (11) 1481-1501
  • 83 Koriyama H, Duff JP, Guerra GG, Chan AW. Sedation Withdrawal and Analgesia Team. Is propofol a friend or a foe of the pediatric intensivist? Description of propofol use in a PICU*. Pediatr Crit Care Med 2014; 15 (02) e66-e71
  • 84 Ho KM, Ng JY. The use of propofol for medium and long-term sedation in critically ill adult patients: a meta-analysis. Intensive Care Med 2008; 34 (11) 1969-1979
  • 85 Lonardo NW, Mone MC, Nirula R. et al. Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care Med 2014; 189 (11) 1383-1394
  • 86 Jakob SM, Ruokonen E, Grounds RM. et al; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012; 307 (11) 1151-1160
  • 87 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 (22) 2644-2653
  • 88 Riker RR, Shehabi Y, Bokesch PM. et al; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009; 301 (05) 489-499
  • 89 Pereira JV, Sanjanwala RM, Mohammed MK, Le ML, Arora RC. Dexmedetomidine versus propofol sedation in reducing delirium among older adults in the ICU: a systematic review and meta-analysis. Eur J Anaesthesiol 2020; 37 (02) 121-131
  • 90 Hughes CG, Mailloux PT, Devlin JW. et al; MENDS2 Study Investigators. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med 2021
  • 91 Louis C, Godet T, Chanques G. et al; AZUREA network. Effects of dexmedetomidine on delirium duration of non-intubated ICU patients (4D trial): study protocol for a randomized trial. Trials 2018; 19 (01) 307
  • 92 Playfor SD, Venkatesh K. Current patterns of propofol use in PICU in the United Kingdom and North America. Paediatr Anaesth 2004; 14 (06) 501-504
  • 93 Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med 2007; 8 (02) 115-131
  • 94 Piastra M, Pizza A, Gaddi S. et al. Dexmedetomidine is effective and safe during NIV in infants and young children with acute respiratory failure. BMC Pediatr 2018; 18 (01) 282
  • 95 Whalen LD, Di Gennaro JL, Irby GA, Yanay O, Zimmerman JJ. Long-term dexmedetomidine use and safety profile among critically ill children and neonates. Pediatr Crit Care Med 2014; 15 (08) 706-714
  • 96 Hauber JA, Davis PJ, Bendel LP. et al. Dexmedetomidine as a rapid bolus for treatment and prophylactic prevention of emergence agitation in anesthetized children. Anesth Analg 2015; 121 (05) 1308-1315
  • 97 Makkar JK, Bhatia N, Bala I, Dwivedi D, Singh PM. A comparison of single dose dexmedetomidine with propofol for the prevention of emergence delirium after desflurane anaesthesia in children. Anaesthesia 2016; 71 (01) 50-57
  • 98 Shukry M, Clyde MC, Kalarickal PL, Ramadhyani U. Does dexmedetomidine prevent emergence delirium in children after sevoflurane-based general anesthesia?. Paediatr Anaesth 2005; 15 (12) 1098-1104
  • 99 Sun Y, Liu J, Yuan X, Li Y. Effects of dexmedetomidine on emergence delirium in pediatric cardiac surgery. Minerva Pediatr 2017; 69 (03) 165-173
  • 100 Sperotto F, Mondardini MC, Dell'Oste C. et al; Pediatric Neurological Protection and Drugs (PeNPAD) Study Group of the Italian Society of Neonatal and Pediatric Anesthesia and Intensive Care (SARNePI). Efficacy and safety of dexmedetomidine for prolonged sedation in the PICU: a prospective multicenter study (PROSDEX). Pediatr Crit Care Med 2020; 21 (07) 625-636
  • 101 Paterson R. Accuracy of delirium assessments in critically ill children: A prospective, observational study during routine care. Aust Crit Care 2020; 34 (03) 226-234