Last Updated: April 21, 2021
Severe cases of COVID-19 may be associated with hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS), septic shock, cardiac dysfunction, elevation in multiple inflammatory cytokines, thromboembolic disease, and/or exacerbation of underlying comorbidities. In addition to pulmonary disease, patients with COVID-19 may also experience cardiac, hepatic, renal, and central nervous system disease. Because patients with critical illness are likely to undergo aerosol-generating procedures, they should be placed in airborne infection isolation rooms, when available.
Guidance on diagnostic testing for SARS-CoV-2 can be found in the Testing for SARS-CoV-2 Infection section.
Most of the recommendations for the management of critically ill patients with COVID-19 are extrapolated from experience with other causes of sepsis.1 Currently, there is limited information to suggest that the critical care management of patients with COVID-19 should differ substantially from the management of other critically ill patients; however, special precautions to prevent environmental contamination by SARS-CoV-2 are warranted.
As with any patient in the intensive care unit (ICU), successful clinical management of a patient with COVID-19 includes treating both the medical condition that initially resulted in ICU admission and other comorbidities and nosocomial complications.
Certain attributes and comorbidities (e.g., older age, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, cancer, renal disease, obesity , sickle cell disease, receipt of a solid organ transplant) are associated with an increased risk of severe illness from COVID-19.2
Bacterial Superinfection of COVID-19-Associated Pneumonia
Limited information exists about the frequency and microbiology of pulmonary coinfections and superinfections in patients with COVID-19, such as hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Some studies from China emphasize the lack of bacterial coinfections in patients with COVID-19, while other studies suggest that these patients experience frequent bacterial complications.3-8 There is appropriate concern about performing pulmonary diagnostic procedures such as bronchoscopy or other airway sampling procedures that require disruption of a closed airway circuit in patients with COVID-19. Thus, while some clinicians do not routinely start empiric broad-spectrum antimicrobial therapy for patients with severe COVID-19 disease, other experienced clinicians routinely use such therapy. However, empiric broad-spectrum antimicrobial therapy is the standard of care for the treatment of shock. Antibiotic stewardship is critical to avoid reflexive or continued courses of antibiotics.
Inflammatory Response Due to COVID-19
Patients with COVID-19 may express increased levels of pro-inflammatory cytokines and anti-inflammatory cytokines, which has previously been referred to as “cytokine release syndrome” or “cytokine storm,” although these are imprecise terms. However, these terms are misnomers because the magnitude of cytokine elevation in patients with COVID-19 is modest compared to that in patients with many other critical illnesses, such as sepsis and ARDS.9,10
Patients with COVID-19 and severe pulmonary involvement are well described to also manifest extrapulmonary disease and to exhibit laboratory markers of acute inflammation. Patients with these manifestations of severe pulmonary disease typically progress to critical illness 10 to 12 days after the onset of COVID-19 symptoms.Multisystem Inflammatory Syndrome in Adults
In addition, there are case reports describing patients who had evidence of acute or recent SARS-CoV-2 infection (documented by a nucleic acid amplification test [NAAT] or antigen or antibody testing) with minimal respiratory symptoms, but with laboratory markers of severe inflammation (e.g., elevated C-reactive protein [CRP], ferritin, D-dimer, cardiac enzymes, liver enzymes, and creatinine) and various other symptoms, including fever and shock; and signs of cardiovascular, gastrointestinal, dermatologic, and neurologic disease. This constellation of signs and symptoms has been designated multisystem inflammatory syndrome in adults (MIS-A).11 To date, most adults in whom MIS-A has been described have survived. This syndrome is similar to a syndrome previously described in children (multisystem inflammatory syndrome in children [MIS-C]).MIS-A is defined by the following criteria:
- A severe illness requiring hospitalization in an individual aged ≥21 years;
- Current or past infection with SARS-CoV-2;
- Severe dysfunction in one or more extrapulmonary organ systems;
- Laboratory evidence of elevated inflammatory markers (e.g., CRP, ferritin, D-dimer, interleukin [IL]-6);
- Absence of severe respiratory illness; and
- Absence of an alternative unifying diagnosis.11
Because there is no specific diagnostic test for MIS-A, diagnosis of this inflammatory syndrome is one of exclusion after other causes (e.g., septic shock) have been eliminated. Although there are currently no controlled clinical trial data in patients with MIS-A to guide treatment of the syndrome, case reports have described the use of intravenous immunoglobulin, corticosteroids, or anti-IL-6 therapy.
COVID-19-Induced Cardiac Dysfunction, Including Myocarditis
A growing body of literature describes cardiac injury or dysfunction in approximately 20% of patients who are hospitalized with COVID-19.4,6,12-15 COVID-19 may be associated with an array of cardiovascular complications, including acute coronary syndrome, myocarditis, arrythmias, and thromboembolic disease.16
Thromboembolic Events and COVID-19
Critically ill patients with COVID-19 have been observed to have a prothrombotic state, which is characterized by the elevation of certain biomarkers, and there is an apparent increase in the incidence of venous thromboembolic disease in this population. In some studies, thromboemboli have been diagnosed in patients who received chemical prophylaxis with heparinoids.17-19 Autopsy studies provide additional evidence of both thromboembolic disease and microvascular thrombosis in patients with COVID-19.20 Some authors have called for routine surveillance of ICU patients for venous thromboembolism.21 See the Antithrombotic Therapy in Patients with COVID-19 section for a more detailed discussion.
Renal and Hepatic Dysfunction Due to COVID-19
Although SARS-CoV-2 is primarily a pulmonary pathogen, renal and hepatic dysfunction are consistently described in patients with severe COVID-19.4 In one case series of patients with critical disease, >15% of the patients required continuous renal replacement therapy.6 See the Acute Kidney Injury and Renal Replacement Therapy section for a more detailed discussion.
Considerations in Children
Several large epidemiologic studies suggest that rates of ICU admission are substantially lower for children with COVID-19 than for adults with the disease. However, severe disease does occur in children.22-27 The risk factors for severe COVID-19 in children have not yet been established. Data from studies of adults with COVID-19 and extrapolation from data on other pediatric respiratory viruses suggest that children who are severely immunocompromised and those with underlying cardiopulmonary disease may be at higher risk for severe COVID-19.
MIS-C, the postinfectious complication of COVID-19 seen in some children, has been described.28,29 Certain symptoms of MIS-C often require ICU-level care, including blood pressure and inotropic support. These symptoms include severe abdominal pain, multisystem inflammation, shock, cardiac dysfunction, and, rarely, coronary artery aneurysm. A minority of children with MIS-C meet the criteria for typical or atypical Kawasaki disease. For details on MIS-C clinical features and the treatments that are being investigated, see the Special Considerations in Children section.
Interactions Between Drugs Used to Treat COVID-19 and Drugs Used to Treat Comorbidities
All ICU patients should be routinely monitored for drug-drug interactions. The potential for drug-drug interactions between investigational medications or medications used off-label to treat COVID-19 and concurrent drugs should be considered.
Sedation Management in Patients with COVID-19
International guidelines provide recommendations on the prevention, detection, and treatment of pain, sedation, and delirium.30,31 Sedation management strategies, such as maintaining a light level of sedation (when appropriate) and minimizing sedative exposure, have shortened the duration of mechanical ventilation and the length of stay in the ICU for patients without COVID-19.32,33The Society of Critical Care Medicine’s (SCCM’s) ICU Liberation Campaign promotes the ICU Liberation Bundle (A-F) to improve post-ICU patient outcomes. The A-F Bundle includes the following elements:
- Assess, prevent, and manage pain;
- Both spontaneous awakening and breathing trials;
- Choice of analgesia and sedation;
- Delirium: assess, prevent, and manage;
- Early mobility and exercise; and
- Family engagement and empowerment.
The A-F Bundle also provides frontline staff with practical application strategies for each element.34 The A-F Bundle should be incorporated using an interprofessional team model. This approach helps standardize communication among team members, improves survival, and reduces long-term cognitive dysfunction of patients.35 Despite the known benefits of the A-F Bundle, its impact has not been directly assessed in patients with COVID-19; however, the use of the Bundle should be encouraged, when appropriate, to improve ICU patient outcomes. Prolonged mechanical ventilation of COVID-19 patients, coupled with deep sedation and potentially neuromuscular blockade, increases the workload of ICU staff. Additionally, significant drug shortages may force clinicians to use older sedatives with prolonged durations of action and active metabolites, impeding routine implementation of the PADIS Guidelines. This puts patients at additional risk for ICU and post-ICU complications.
Post-Intensive Care Syndrome
Patients with COVID-19 are reported to experience prolonged delirium and/or encephalopathy. Risk factors that are associated with delirium include the use of mechanical ventilation; the use of restraints; the use of benzodiazepine, opioid, and vasopressor infusions; and the use of antipsychotics.36,37 Neurological complications are associated with older age and underlying conditions, such as hypertension and diabetes mellitus.38 Autopsy studies have reported both macrovascular and microvascular thrombosis, with evidence of hypoxic ischemia.39 Adequate management requires careful attention to best sedation practices and vigilance in stroke detection.
Post-intensive care syndrome (PICS) is a spectrum of cognitive, psychiatric, and/or physical disability that affects survivors of critical illness and persists after a patient leaves the ICU.40 Patients with PICS may present with varying levels of impairment; including profound muscle weakness (ICU-acquired weakness); problems with thinking and judgment (cognitive dysfunction); and mental health problems, such as problems sleeping, post-traumatic stress disorder (PTSD), depression, and anxiety. ICU-acquired weakness affects 33% of all patients who receive mechanical ventilation, 50% of patients with sepsis, and ≤50% of patients who remain in the ICU for ≥1 week.41-43 Cognitive dysfunction affects 30% to 80% of patients discharged from the ICU.44-46 About 50% of ICU survivors do not return to work within 1 year after discharge.47 Although no single risk factor has been associated with PICS, there are opportunities to minimize the risk of PICS through medication management (using the A-F Bundle), physical rehabilitation, follow-up clinics, family support, and improved education about the syndrome. PICS also affects family members who participate in the care of their loved ones. In one study, a third of family members who had main decision-making roles experienced mental health problems, such as depression, anxiety, and PTSD.48
Early reports suggest that some patients with COVID-19 who have been treated in the ICU express manifestations of PICS.49 Although specific therapies for COVID-19-induced PICS are not yet available, physicians should maintain a high index of suspicion for cognitive impairment and other related problems in survivors of severe or critical COVID-19 illness.
Other Intensive Care Unit-Related Complications
Patients who are critically ill with COVID-19 are at risk for nosocomial infections and other complications of critical illness care, such as VAP, HAP, catheter-related bloodstream infections, and venous thromboembolism. When treating patients with COVID-19, clinicians also need to minimize the risk of conventional ICU complications to optimize the likelihood of a successful ICU outcome.
Advance Care Planning and Goals of Care
The advance care plans and the goals of care for all critically ill patients must be assessed at hospital admission and regularly thereafter. This is an essential element of care for all patients. Information on palliative care for patients with COVID-19 can be found at the National Coalition for Hospice and Palliative Care website.
To guide shared decision-making in cases of serious illness, advance care planning should include identifying existing advance directives that outline a patient’s preferences and values. Values and care preferences should be discussed, documented, and revisited regularly for patients with or without prior directives. Specialty palliative care teams can facilitate communication between clinicians and surrogate decision makers, support frontline clinicians, and provide direct patient care services when needed.
Surrogate decision makers should be identified for all critically ill patients with COVID-19 at hospital admission. Infection-control policies for COVID-19 often create communication barriers for surrogate decision makers, and most surrogates will not be physically present when discussing treatment options with clinicians. Many decision-making discussions will occur via telecommunication.
The Surviving Sepsis Campaign (SSC), an initiative supported by the SCCM and the European Society of Intensive Care Medicine, issued Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) in March 2020.1 The COVID-19 Treatment Guidelines Panel (the Panel) has based the recommendations in this section on the SSC COVID-19 Guidelines with permission, and the Panel gratefully acknowledges the work of the SSC COVID-19 Guidelines Panel. The Panel also acknowledges the contributions and expertise of Andrew Rhodes, MBBS, MD, of St. George’s University Hospitals in London, England, and Waleed Alhazzani, MBBS, MSc, of McMaster University in Hamilton, Canada.
- Alhazzani W, Moller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 20200;48(6):e440-e469. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32224769.
- Centers for Disease Control and Prevention. Evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from COVID-19. 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/evidence-table.html. Accessed December 8, 2020.
- Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32167524.
- Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. JAMA. 2020;323(16):1612-1614. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32191259.
- Bhatraju PK, Ghassemieh BJ, Nichols M, et al. COVID-19 in critically ill patients in the Seattle region—case series. N Engl J Med. 2020;382(21):2012-2022. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32227758.
- Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32105632.
- Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32217556.
- Du Y, Tu L, Zhu P, et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational study. Am J Respir Crit Care Med. 2020;201(11):1372-1379. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32242738.
- Leisman DE, Ronner L, Pinotti R, et al. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med. 2020;8(12):1233-1244. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33075298.
- Sinha P, Matthay MA, Calfee CS. Is a "cytokine storm" relevant to COVID-19? JAMA Intern Med. 2020;180(9):1152-1154. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32602883.
- Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection—United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(40):1450-1456. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33031361.
- Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802-810. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32211816.
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31986264.
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32171076.
- Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32031570.
- Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020;17(9):543-558. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32690910.
- Llitjos JF, Leclerc M, Chochois C, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost. 2020;18(7):1743-1746. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32320517.
- Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-1098. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32367170.
- Klok FA, Kruip M, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32291094.
- Menter T, Haslbauer JD, Nienhold R, et al. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32364264.
- Tavazzi G, Civardi L, Caneva L, Mongodi S, Mojoli F. Thrombotic events in SARS-CoV-2 patients: an urgent call for ultrasound screening. Intensive Care Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32322918.
- Sun D, Li H, Lu XX, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J Pediatr. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32193831.
- Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 Among Children in China. Pediatrics. 2020;145(6). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32179660.
- Centers for Disease Control and Prevention. Coronavirus disease 2019 in children—United States, February 12–April 2, 2020. 2020. Available at: https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm. Accessed January 5, 2021.
- Chao JY, Derespina KR, Herold BC, et al. Clinical characteristics and outcomes of hospitalized and critically ill children and adolescents with coronavirus disease 2019 (COVID-19) at a tertiary care medical center in New York City. J Pediatr. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32407719.
- Zachariah P, Johnson CL, Halabi KC, et al. Epidemiology, clinical features, and disease severity in patients with coronavirus disease 2019 (COVID-19) in a children's hospital in New York City, New York. JAMA Pediatr. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32492092.
- DeBiasi RL, Song X, Delaney M, et al. Severe COVID-19 in children and young adults in the Washington, DC metropolitan region. J Pediatr. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32405091.
- Whittaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32511692.
- Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32410760.
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