Introduction to Critical Care Management of Children With COVID-19
Last Updated: May 31, 2022
COVID-19 may lead to critical illness in children, including hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS), septic shock, cardiac dysfunction, thromboembolic disease, hepatic or renal dysfunction, central nervous system disease, and exacerbation of underlying comorbidities. In addition, multisystem inflammatory syndrome in children (MIS-C) is a rare, postinfectious complication of SARS-CoV-2 and is frequently associated with critical illness.
Data informing the optimal management of children with acute COVID-19 or MIS-C are limited. In general, management should follow the principles of pediatric critical care usually applied to non-COVID-19-related illness, such as the Pediatric Acute Lung Injury Consensus Conference (PALICC) recommendations and the Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. For patients with COVID-19 in the intensive care unit (ICU), treatment often requires managing underlying illnesses other than COVID-19 that may have contributed to the need for ICU admission, as well as managing COVID-19 complications. Finally, prevention of ICU-related complications is critical to achieving optimal clinical outcomes for any patient admitted to the ICU.
Selected Clinical Manifestations of COVID-19 Critical Illness
Patients with COVID-19 may develop a hyperinflammatory state, which appears to be distinct from classic “cytokine storm” syndromes (e.g., macrophage activation syndrome in juvenile idiopathic arthritis, familial hemophagocytic lymphohistiocytosis). This phenomenon is less well-described in children than in adults.
Multisystem Inflammatory Syndrome in Children
MIS-C is a rare, postinfectious complication of SARS-CoV-2 that is characterized by persistent fever, systemic inflammation, and multisystem organ dysfunction. The majority of children with MIS-C require ICU-level care, primarily for shock and for vasopressor and inotropic support.1-3 For details on the definition of MIS-C, clinical features, and recommended treatments, see Special Considerations in Children and Therapeutic Management of Hospitalized Pediatric Patients With Multisystem Inflammatory Syndrome in Children (MIS-C) (With Discussion on Multisystem Inflammatory Syndrome in Adults [MIS-A]).
Cardiac Dysfunction, Including Myocarditis
Although cardiac involvement is common in patients with MIS-C,2,4 cardiac manifestations have rarely been described in children with acute COVID-19. Myocarditis, cardiac conduction abnormalities, and coronary artery aneurysms have been reported in patients with MIS-C. Myocarditis may also occur after SARS-CoV-2 vaccination, particularly in adolescent males, although the clinical course generally is relatively mild.5
Limited data characterize the prevalence of thromboembolic disease in children with COVID-19 or MIS-C. In a multicenter, retrospective cohort study including 814 hospitalized patients with COVID-19 or MIS-C, thromboembolic events were detected in 2.1% of patients with COVID-19 and 6.5% of patients with MIS-C.6 The same study conducted a multivariable analysis and found that the following variables were associated with increased risk of thromboembolic events: children aged ≥12 years, MIS-C, central venous catheters, and underlying malignancies. See Antithrombotic Therapy in Patients With COVID-19 for additional recommendations.
Acute Kidney Injury
Acute kidney injury is estimated to occur in 12% to 44% of hospitalized children with COVID-19 or MIS-C, but the need for renal replacement therapy is extremely rare.7-10
Neurologic involvement is common in children with COVID-19 or MIS-C and is estimated to occur in approximately 30% to 40% of children hospitalized with these conditions.2,11 Severe neurologic manifestations, including severe encephalopathy, stroke, demyelinating conditions, cerebral edema, and Guillain-Barré syndrome, have also been described.11
Important Considerations in the Care of Critically Ill Patients With COVID-19
Considerations for the care of children with COVID-19 or MIS-C should generally follow the usual principles of pediatric critical care. Sedation management and considerations related to post-intensive care syndrome–pediatric (PICS-p) are discussed below. See Oxygenation and Ventilation for Children, Hemodynamic Considerations for Children, and Extracorporeal Membrane Oxygenation for Children for more information on pediatric critical care.
Guidelines for the management of pain, agitation, neuromuscular blockade, delirium, and early mobility (PANDEM) in infants and children admitted to the pediatric ICU have recently been published.12 In general, children with COVID-19 or MIS-C who require mechanical ventilation should be managed per the usual critical care for patients with respiratory failure who require mechanical ventilation. The usual care includes sedation with the minimal effective dose required to tolerate mechanical ventilation, optimize gas exchange, and minimize the risk of ventilator-induced lung injury. Using validated pain and sedation scales, the critical care team should set a sedation/pain target based on the phase of ventilation.
Two large randomized controlled trials examined the use of protocols to manage sedation titration in children receiving mechanical ventilation.13,14 In both studies, participants received usual care or protocol-driven care implemented by nurses. The studies found that the use of the protocols did not demonstrate a significant benefit on outcomes, such as the duration of ventilation. However, a patient’s risk of harm from protocolized sedation is generally low, which led the Society of Critical Care Medicine to issue a conditional recommendation, based on low-level evidence, in its PANDEM clinical practice guidelines suggesting the use of protocolized sedation in children who are critically ill and receiving mechanical ventilation.12
Studies evaluating data on the effect of early mobility protocols on critically ill children are limited. One trial evaluated the safety and feasibility of early mobilization in 58 patients who were randomized to receive usual care or early physical therapy, occupational therapy, and speech therapy consultation within 72 hours of admission to the pediatric ICU.15 Although no differences between the arms were demonstrated for clinical, functional, or quality of life outcomes, the study found that the early rehabilitation consultations were safe and feasible.
Ongoing trials are measuring the effect of early mobilization on patient-centered outcomes in children receiving mechanical ventilation. The PANDEM guideline statement issued by the Society of Critical Care Medicine conditionally recommends, based on a low quality of evidence, implementing early mobilization strategies in children when feasible, which likely would apply to children with COVID-19 or MIS-C.12
Post-Intensive Care Syndrome
In recent years, there has been a growing awareness that PICS can occur in pediatric patients. PICS-p has been demonstrated to have a multifaceted effect on the physical, cognitive, emotional, and social health of child survivors of critical illness and their families.16 Furthermore, many pediatric survivors of sepsis or ARDS manifest significant impairments in physical, cognitive, and emotional health.17-19 Although no clear data characterize the prevalence of PICS-p or long-term morbidity in children with COVID-19 or MIS-C, the prevalence is expected to be similar to that observed in other populations with similar illness severities.
For these pediatric recommendations, the COVID-19 Treatment Guidelines Panel integrated the recommendations from pediatric-specific guidelines, including the European Society of Paediatric and Neonatal Intensive Care’s recommendations20 for the care of critically ill children with COVID-19 and the Surviving Sepsis Campaign’s perspective on managing sepsis in children with COVID-19.21 In addition, recommendations from several non-COVID-19-specific treatment guidelines, such as the Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children,22 the PALICC recommendations,23 and the Society of Critical Care Medicine’s PANDEM guidelines,12 were integrated.
- Abrams JY, Oster ME, Godfred-Cato SE, et al. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health. 2021;5(5):323-331. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33711293.
- Feldstein LR, Tenforde MW, Friedman KG, et al. Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. JAMA. 2021;325(11):1074-1087. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33625505.
- Alsaied T, Tremoulet AH, Burns JC, et al. Review of cardiac involvement in multisystem inflammatory syndrome in children. Circulation. 2021;143(1):78-88. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33166178.
- Valverde I, Singh Y, Sanchez-de-Toledo J, et al. Acute cardiovascular manifestations in 286 children with multisystem inflammatory syndrome associated with COVID-19 infection in Europe. Circulation. 2021;143(1):21-32. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33166189.
- Jain SS, Steele JM, Fonseca B, et al. COVID-19 vaccination-associated myocarditis in adolescents. Pediatrics. 2021;148(5):e2021053427. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34389692.
- Whitworth H, Sartain SE, Kumar R, et al. Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood. 2021;138(2):190-198. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33895804.
- Raina R, Chakraborty R, Mawby I, et al. Critical analysis of acute kidney injury in pediatric COVID-19 patients in the intensive care unit. Pediatr Nephrol. 2021;36(9):2627-2638. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33928439.
- Kari JA, Shalaby MA, Albanna AS, et al. Acute kidney injury in children with COVID-19: a retrospective study. BMC Nephrol. 2021;22(1):202. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34059010.
- Basalely A, Gurusinghe S, Schneider J, et al. Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19. Kidney Int. 2021;100(1):138-145. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33675848.
- Bjornstad EC, Krallman KA, Askenazi D, et al. Preliminary assessment of acute kidney injury in critically ill children associated with SARS-CoV-2 infection: a multicenter cross-sectional analysis. Clin J Am Soc Nephrol. 2021;16(3):446-448. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33144276.
- LaRovere KL, Riggs BJ, Poussaint TY, et al. Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome. JAMA Neurol. 2021;78(5):536-547. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33666649.
- Smith HAB, Besunder JB, Betters KA, et al. 2022 Society of Critical Care Medicine clinical practice guidelines on prevention and management of pain, agitation, neuromuscular blockade, and delirium in critically ill pediatric patients with consideration of the ICU environment and early mobility. Pediatr Crit Care Med. 2022;23(2):e74-e110. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35119438.
- Curley MA, Wypij D, Watson RS, et al. Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute respiratory failure: a randomized clinical trial. JAMA. 2015;313(4):379-389. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25602358.
- Blackwood B, Tume LN, Morris KP, et al. Effect of a sedation and ventilator liberation protocol vs usual care on duration of invasive mechanical ventilation in pediatric intensive care units: a randomized clinical trial. JAMA. 2021;326(5):401-410. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34342620.
- Fink EL, Beers SR, Houtrow AJ, et al. Early protocolized versus usual care rehabilitation for pediatric neurocritical care patients: a randomized controlled trial. Pediatr Crit Care Med. 2019;20(6):540-550. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30707210.
- Manning JC, Pinto NP, Rennick JE, Colville G, Curley MAQ. Conceptualizing post intensive care syndrome in children—the PICS-p framework. Pediatr Crit Care Med. 2018;19(4):298-300. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29406379.
- Herrup EA, Wieczorek B, Kudchadkar SR. Characteristics of postintensive care syndrome in survivors of pediatric critical illness: a systematic review. World J Crit Care Med. 2017;6(2):124-134. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28529914.
- Keim G, Watson RS, Thomas NJ, Yehya N. New morbidity and discharge disposition of pediatric acute respiratory distress syndrome survivors. Crit Care Med. 2018;46(11):1731-1738. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30024428.
- Watson RS, Asaro LA, Hutchins L, et al. Risk factors for functional decline and impaired quality of life after pediatric respiratory failure. Am J Respir Crit Care Med. 2019;200(7):900-909. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31034245.
- Rimensberger PC, Kneyber MCJ, Deep A, et al. 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. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33003177.
- Weiss SL, Peters MJ, Agus MSD, et al. Perspective of the Surviving Sepsis Campaign on the management of pediatric sepsis in the era of coronavirus disease 2019. Pediatr Crit Care Med. 2020;21(11):e1031-e1037. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32886460.
- Weiss SL, Peters MJ, Alhazzani W, et al. Surviving Sepsis Campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med. 2020;21(2):e52-e106. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32032273.
- Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2015;16(5):428-439. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25647235.