Pediatric delirium in times of COVID-19

Roberta Esteves Vieira de Castro Miguel Rodríguez-Rubio Maria Clara de Magalhães-Barbosa Arnaldo Prata-Barbosa About the authors

Introduction

Delirium is defined as a neurocognitive syndrome characterized by the acute onset of brain dysfunction with fluctuations in the basal mental state, inattention and disorganized thinking or altered levels of consciousness.(11 Bettencourt A, Mullen JE. Delirium in children: identification, prevention, and management. Crit Care Nurse. 2017;37(3):e9-18.,22 De Castro RE, de Magalhães-Barbosa MC, Cunha AJ, Cheniaux E, Prata-Barbosa A. Delirium detection based on the clinical experience of pediatric intensivists. Pediatr Crit Care Med. 2020;21(9):e869-73.) It is a frequent complication in intensive care units (ICUs).(33 Page VJ, Ely EW. Delirium in critical care. 2nd ed. Cambridge, UK: Cambridge University Press; 2015.) Its occurrence is strongly predictive of an increase in the duration of mechanical ventilation (MV), length of stay in the ICU and hospital, risk of falls, hospital costs and mortality.(44 Marra A, Boehm LM, Kotfis K, Pun BT. Monitoring for delirium in critically ill adults. In: Hughes C, Pandharipande P, Ely EW, editors. Delirium. Acute brain dysfunction in the critically ill. Cham, Switzerland: Springer; 2020. p. 13-25.)

Data from the literature show that the exact incidence of delirium in pediatric patients is still unknown and ranges from 0.84% to 66%. The prevalence is also quite variable at between 13% and 66% and has been well characterized since the implementation of valid screening tools for delirium in pediatric populations. Higher prevalence values of between 50% and approximately 70% were reported in critically ill children under 5 years of age, those on MV, during the postoperative period of cardiac surgery and during the immediate postoperative period after general anesthesia and elective surgery. However, underdiagnosis or incorrect diagnosis of delirium may occur when it is based only on the clinical experience of the team, without the use of a valid and reliable tool.(22 De Castro RE, de Magalhães-Barbosa MC, Cunha AJ, Cheniaux E, Prata-Barbosa A. Delirium detection based on the clinical experience of pediatric intensivists. Pediatr Crit Care Med. 2020;21(9):e869-73.,55 Barnes SS, Gabor C, Kudchadkar SR. Epidemiology of Delirium in Children: Prevalence, Risk Factors, and Outcomes. In: Hughes C, Pandharipande P, Ely EW (eds) Delirium. Cham: Springer; 2020. p. 93-102.,66 Smith HA, Williams SR. Pediatric delirium assessment, prevention, and management. In: Hughes C, Pandharipande P, Ely EW, editors. Delirium. Acute brain dysfunction in the critically ill. Cham, Switzerland: Springer; 2020. p. 73-92.)

Considering the high prevalence of delirium in the ICU, it is believed to be affect at least one quarter of patients aged 65 years or older infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more than two-thirds of patients with the most severe cases of coronavirus disease 2019 (COVID-19).(77 Oldham MA, Slooter AJ, Cunningham C, Rahman S, Davis D, Vardy ER, et al. Characterising neuropsychiatric disorders in patients with COVID-19. Lancet Psychiatry. 2020;7(11):932-3.) However, delirium occurs not only in adults and the elderly but also in children and adolescents and has been associated with a wide spectrum of deleterious outcomes at all ages.(88 Schieveld JN, Janssen NJ, Strik JJ. On the importance of addressing pediatric delirium phenotypes and neurocognitive functioning: pediatric critical illness brain injury in COVID times. Crit Care Med. 2020;48(12):1911-3.)

Although the number of pediatric patients affected by COVID-19 is small compared to the number of affected adult and geriatric patients, children are also at risk of becoming seriously ill, especially in the presence of underlying diseases.(88 Schieveld JN, Janssen NJ, Strik JJ. On the importance of addressing pediatric delirium phenotypes and neurocognitive functioning: pediatric critical illness brain injury in COVID times. Crit Care Med. 2020;48(12):1911-3.) Numerous studies have described these patients as less vulnerable and more predisposed to mild COVID-19. However, even with recent data on the reduced lethality of COVID-19 in pediatric patients in 2021 compared to 2020, children and adolescents may develop severe conditions, such as acute respiratory distress syndrome or multisystemic inflammatory syndrome.(99 Rimensberger PC, Kneyber MC, Deep A, Bansal M, Hoskote A, Javouhey E, Jourdain G, Latten L, MacLaren G, Morin L, Pons-Odena M, Ricci Z, Singh Y, Schlapbach LJ, Scholefield BR, Terheggen U, Tissières P, Tume LN, Verbruggen S, Brierley J; European Society of Pediatric and Neonatal Intensive Care (ESPNIC) Scientific Sections’ Collaborative Group. Caring for Critically Ill Children with Suspected or Proven Coronavirus Disease 2019 Infection: Recommendations by the Scientific Sections’ Collaborative of the European Society of Pediatric and Neonatal Intensive Care. Pediatr Crit Care Med. 2021;22(1):56-67.

10 Prata-Barbosa A, Lima-Setta F, Santos GR, Lanziotti VS, de Castro RE, de Souza DC, Raymundo CE, de Oliveira FR, de Lima LF, Tonial CT, Colleti J Jr, Bellinat AP, Lorenzo VB, Zeitel RS, Pulcheri L, Costa FC, La Torre FP, Figueiredo EA, Silva TP, Riveiro PM, Mota IC, Brandão IB, de Azevedo ZM, Gregory SC, Boedo FR, de Carvalho RN, Castro NA, Genu DH, Foronda FA, Cunha AJ, de Magalhães-Barbosa MC; Brazilian Research Network in Pediatric Intensive Care, (BRnet-PIC). Pediatric patients with COVID-19 admitted to intensive care units in Brazil: a prospective multicenter study. J Pediatr (Rio J). 2020;96(5):582-92.
-1111 Sociedade Brasileira de Pediatria (SBP). Nota Técnica. Dados Epidemiológicos da COVID-19 em Pediatria. 17 de março de 2021. Disponível em: https://www.sbp.com.br/fileadmin/user_upload/22972b-NT_-_Dados_Epidem_COVID-19_em_Pediatria.pdf
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Although there are still many difficulties in determining the best COVID-19 management strategy, the need to maintain good clinical management practices is undeniable, especially during the pandemic.(1212 Devlin JW, O’Neal HR Jr, Thomas C, Barnes Daly MA, Stollings JL, Janz DR, et al. Strategies to optimize ICU liberation (A to F) bundle performance in critically ill adults with coronavirus disease 2019. Crit Care Explor. 2020;2(6):e0139.

13 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJ, 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):e825-73.
-1414 O’Hanlon S, Inouye SK. Delirium: a missing piece in the COVID-19 pandemic puzzle. Age Ageing. 2020;49(4):497-8.) In this context, the occurrence of delirium in critically ill children with COVID-19 must be monitored. Delirium is a frequent manifestation in infectious conditions and can be considered an early marker of acute disease, in addition to being associated with long-term cognitive complications.(1313 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJ, 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):e825-73.,1515 Vázquez JC, Redolar-Ripoli D. Delirium in severe acute respiratory syndrome - coronavirus-2 infection: a point of view. J Clin Immunol Immunother. 2020;6(4):039.) Due to the development of valid and reliable tools for the diagnosis of delirium in pediatrics, it is now known that one in four children hospitalized in the ICU is likely to present it.(55 Barnes SS, Gabor C, Kudchadkar SR. Epidemiology of Delirium in Children: Prevalence, Risk Factors, and Outcomes. In: Hughes C, Pandharipande P, Ely EW (eds) Delirium. Cham: Springer; 2020. p. 93-102.) Its prevalence may be higher in special subgroups, such as patients undergoing cardiac surgery or extracorporeal membrane oxygenation.(55 Barnes SS, Gabor C, Kudchadkar SR. Epidemiology of Delirium in Children: Prevalence, Risk Factors, and Outcomes. In: Hughes C, Pandharipande P, Ely EW (eds) Delirium. Cham: Springer; 2020. p. 93-102.,1616 Patel AK, Biagas KV, Clarke EC, Gerber LM, Mauer E, Silver G, et al. Delirium in children after cardiac bypass surgery. Pediatr Crit Care Med. 2017;18(2):165-71.) The recognition of delirium in pediatrics is extremely relevant because it has been independently associated with increased costs in the pediatric ICU, prolonged hospital stays and increased in-hospital mortality.(55 Barnes SS, Gabor C, Kudchadkar SR. Epidemiology of Delirium in Children: Prevalence, Risk Factors, and Outcomes. In: Hughes C, Pandharipande P, Ely EW (eds) Delirium. Cham: Springer; 2020. p. 93-102.,1717 Traube C, Silver G, Gerber LM, Kaur S, Mauer EA, Kerson A, et al. Delirium and mortality in critically ill children: epidemiology and outcomes of pediatric delirium. Crit Care Med. 2017;45(5):891-8.,1818 Traube C, Mauer EA, Gerber LM, Kaur S, Joyce C, Kerson A, et al. Cost associated with pediatric delirium in the ICU. Crit Care Med. 2016;44(12):e1175-9.)

Risk factors for delirium in patients with COVID-19

Often, delirium is triggered by more than one risk factor. The probability of its occurrence increases with the increase in the number of these factors, and an understanding of this association is essential for identifying potentially reversible causes. Delirium emerges as the result of an intricate relationship between vulnerability factors and precipitating factors, i.e., a patient with high vulnerability may develop it in the presence of a minor injury, while one with few predisposing factors may require more intense injuries to develop it.(1919 Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA. 1996;275(11):852-7.)

Important factors that predispose pediatric patients to the development of delirium include age less than 2 years and a history of neurodevelopmental delay. Patients with immature or abnormal brains are more prone to developing delirium, as are elderly individuals and patients with underlying dementia.(2020 Patel AK, Bell MJ, Traube C. Delirium in pediatric critical care. Pediatr Clin North Am. 2017;64(5):1117-32.) Other predisposing factors are previous comorbidities, the severity of the underlying disease, malnutrition (associated with a serum albumin level below 3.0g/dL) and MV dependence. Predisposing factors are inherent to the patient and cannot be modified. The most frequent precipitating factors in pediatrics include the use of benzodiazepines and anticholinergic drugs, cardiac bypass surgeries, bed immobilization, prolonged hospitalization in the pediatric ICU, use of physical restraints, pain and withdrawal syndrome. These factors act as triggers and can be modified by the health team in many cases.(2020 Patel AK, Bell MJ, Traube C. Delirium in pediatric critical care. Pediatr Clin North Am. 2017;64(5):1117-32.,2121 Harris J, Ramelet AS, van Dijk M, Pokorna P, Wielenga J, Tume L, 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(6):972-86.)

The development of delirium is closely related to the severity of the disease. In the context of SARS-CoV-2 infection, recent studies have shown that delirium may be triggered by factors such as hypoxia and the resulting deficiency in cerebral oxygenation; neuronal inflammation due to the cytokine storm resulting from an unbalanced immune system activation; and/or direct invasion of the central nervous system by the virus, which has neuronal toxicity.(1515 Vázquez JC, Redolar-Ripoli D. Delirium in severe acute respiratory syndrome - coronavirus-2 infection: a point of view. J Clin Immunol Immunother. 2020;6(4):039.) In addition to factors associated with COVID-19, such as neuroinflammation, multiple organ failure and increased risk of thrombosis, treatment-related factors may increase the risk of delirium. These factors include the use of prolonged MV with deep sedation and the iatrogenic environment of the pediatric ICU, which is marked by intense sleep deprivation.(88 Schieveld JN, Janssen NJ, Strik JJ. On the importance of addressing pediatric delirium phenotypes and neurocognitive functioning: pediatric critical illness brain injury in COVID times. Crit Care Med. 2020;48(12):1911-3.,2222 Castro RE, Garcez FB, Avelino-Silva TJ. Patient care during the COVID-19 pandemic: do not leave delirium behind. Braz J Psychiatry. 2021;43(2):127-8.) In addition to these factors, there is the need for isolation imposed by COVID-19 to reduce the exposure of health professionals, which decreases contact with the team and may be aggravated by the scarcity of personal protective equipment (PPE). Although this isolation is understandable given the intensity of the pandemic, this reality increases patients’ isolation and immobility and, when associated with the numerous complications of the disease, produces an extremely iatrogenic environment with a high risk of delirium.(2323 LaHue SC, James TC, Newman JC, Esmaili AM, Ormseth CH, Ely EW. Collaborative delirium prevention in the age of COVID-19. J Am Geriatr Soc. 2020;68(5):947-9.)

Strategies for the prevention and management of delirium in pediatric ICUs during the COVID-19 pandemic

The measures adopted to prevent the spread of SARS-CoV-2, such as the use of PPE and restrictive visitation policies, in addition to the scarcity of professionals available for care (which reduces the time available for evaluations), may hinder the recognition of delirium and create barriers for the implementation of recommended nonpharmacological strategies. In addition, these measures may impair patient orientation and are a significant risk factor for the development of delirium.(2222 Castro RE, Garcez FB, Avelino-Silva TJ. Patient care during the COVID-19 pandemic: do not leave delirium behind. Braz J Psychiatry. 2021;43(2):127-8.)

Although extremely relevant, delirium is often unrecognized, and the pandemic has presented numerous obstacles to its diagnosis.(1212 Devlin JW, O’Neal HR Jr, Thomas C, Barnes Daly MA, Stollings JL, Janz DR, et al. Strategies to optimize ICU liberation (A to F) bundle performance in critically ill adults with coronavirus disease 2019. Crit Care Explor. 2020;2(6):e0139.,2222 Castro RE, Garcez FB, Avelino-Silva TJ. Patient care during the COVID-19 pandemic: do not leave delirium behind. Braz J Psychiatry. 2021;43(2):127-8.,2323 LaHue SC, James TC, Newman JC, Esmaili AM, Ormseth CH, Ely EW. Collaborative delirium prevention in the age of COVID-19. J Am Geriatr Soc. 2020;68(5):947-9.) A team effort is required to adopt strategies that reduce these barriers. One of the most efficient resources is the adequate use of validated tools for screening for delirium in critically ill children.(88 Schieveld JN, Janssen NJ, Strik JJ. On the importance of addressing pediatric delirium phenotypes and neurocognitive functioning: pediatric critical illness brain injury in COVID times. Crit Care Med. 2020;48(12):1911-3.) The diagnostic criteria for delirium represent a valid and operationalized construct with high reliability and remarkable clinical application. The use of homogeneous and validated nomenclature can help the team avoid vague terms, such as “altered mental state”, thus enabling the incorporation of standardized strategies for the management of delirium while facilitating communication with patients, family members and among themselves and other health professionals.(77 Oldham MA, Slooter AJ, Cunningham C, Rahman S, Davis D, Vardy ER, et al. Characterising neuropsychiatric disorders in patients with COVID-19. Lancet Psychiatry. 2020;7(11):932-3.)

Table 1 presents some proposed measures for the prevention and management of delirium in pediatric patients that have been adapted to the context of the pandemic. These measures do not require the implementation of complex actions and do not increase the risk of exposure for health professionals. It is believed that, as with any serious childhood disorder, the prevention, evaluation and treatment of delirium should be part of the approach taken for pediatric patients with COVID-19. Investing time in this approach can avoid costs and associated complications.

Table 1
Recommendations for the diagnosis, prevention and treatment of delirium in pediatric patients with COVID-19

References

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    Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA. 1996;275(11):852-7.
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Publication Dates

  • Publication in this collection
    24 Jan 2022
  • Date of issue
    2021

History

  • Received
    04 Apr 2021
  • Accepted
    01 Aug 2021
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