What is the recommended critical care management for an adult patient with a confirmed diagnosis of COVID-19, potentially with severe symptoms, including respiratory status, oxygen saturation, and overall clinical condition, considering treatment options such as antiviral medications like remdesivir, corticosteroids like dexamethasone, and convalescent plasma therapy?

Critical Care Management of Severe COVID-19

Immediate Respiratory Support Strategy

For adults with severe COVID-19 requiring critical care, initiate supportive oxygen therapy targeting SpO2 88-95%, use systemic corticosteroids (dexamethasone 6 mg daily) for those requiring supplemental oxygen, and consider remdesivir within 7 days of symptom onset, while avoiding routine convalescent plasma therapy. 1, 2, 3

Defining Severe COVID-19

Severe disease in adults is defined by meeting any of the following criteria 1:

• Respiratory rate ≥30 breaths/min
• Oxygen saturation ≤93% on room air at rest
• PaO2/FiO2 ≤300 mmHg
• Progressive worsening with >50% lung lesion progression within 24-48 hours

Oxygen and Respiratory Support Algorithm

Non-Invasive Support

• High-flow nasal oxygen (HFNC) or non-invasive positive pressure ventilation (NIPPV) should be initiated for patients with SpO2 <90% despite conventional oxygen therapy 1
• Monitor closely for worsening respiratory status and perform early intubation in a controlled setting if deterioration occurs after 1-2 hours of failed HFNC/NIPPV trial 1, 4
• Target SpO2 88-95% to avoid hyperoxia while ensuring adequate tissue oxygenation 4

Mechanical Ventilation Settings

If intubation becomes necessary 1, 4:

• Tidal volume: 4-8 mL/kg predicted body weight (strong recommendation)
• Plateau pressure: <30 cmH2O (strong recommendation)
• Higher PEEP strategy: >10 cmH2O for moderate-to-severe ARDS (strong recommendation)
• Conservative fluid strategy targeting net-even to negative fluid balance once hemodynamically stable (weak recommendation)

Advanced Respiratory Interventions

• Prone positioning for 12-16 hours daily in moderate-to-severe ARDS improves oxygenation and reduces mortality 1, 4
• Use intermittent boluses of neuromuscular blocking agents as needed to facilitate lung-protective ventilation, reserving continuous infusion only for persistent ventilator dyssynchrony or high plateau pressures 1, 4
• VV-ECMO should be considered for refractory hypoxemia despite optimized ventilation, neuromuscular blockade, and prone positioning, but only in carefully selected patients at experienced centers 1, 4

Pharmacologic Management

Corticosteroids (First-Line Therapy)

Dexamethasone 6 mg daily is strongly recommended for mechanically ventilated COVID-19 patients with ARDS, as it decreases mortality. 1, 2, 4

• Use systemic corticosteroids in mechanically ventilated patients with ARDS (weak recommendation, but majority consensus supports use in sickest patients) 1
• Avoid corticosteroids in mechanically ventilated patients with respiratory failure but without ARDS 1, 4
• Consider combining glucocorticoids with tocilizumab for hospitalized patients to reduce disease progression and mortality 2

Remdesivir (Antiviral Therapy)

Remdesivir should be initiated as soon as possible after diagnosis and within 7 days of symptom onset. 3

Dosing for adults and pediatric patients ≥40 kg 3:

• Loading dose: 200 mg IV on Day 1
• Maintenance: 100 mg IV once daily from Day 2

Treatment duration 3:

• 10 days for patients requiring invasive mechanical ventilation and/or ECMO
• 5 days for hospitalized patients not requiring invasive mechanical ventilation/ECMO (may extend up to 10 days total if no clinical improvement)

Administration requirements 3:

• Must be administered by IV infusion only in settings with immediate access to medications for severe infusion/hypersensitivity reactions and ability to activate emergency medical system
• Perform hepatic laboratory testing and prothrombin time before starting and monitor during treatment
• No dosage adjustment needed for any degree of renal impairment, including dialysis patients

Combined therapy: Remdesivir plus dexamethasone in severe patients requiring HFOT or NIV was associated with reduced 28-day intubation rate (19.7% vs 48.5%) without increased laboratory abnormalities or clinical complications 5

Convalescent Plasma (NOT Recommended)

Convalescent plasma should NOT be routinely used in critically ill COVID-19 patients, as high-quality evidence demonstrates it does not improve outcomes. 1, 6, 7

• The Surviving Sepsis Campaign suggests against routine use of convalescent plasma in critically ill adults 1
• A large RCT (REMAP-CAP) with 2,011 critically ill patients found convalescent plasma had a 99.4% posterior probability of futility, with no improvement in organ support-free days (median 0 vs 3 days) or mortality (37.3% vs 38.4%) 6
• Cochrane systematic review of 33 RCTs with 24,861 participants confirms convalescent plasma does not reduce mortality (RR 0.98,95% CI 0.92-1.03) and has little to no impact on clinical outcomes in moderate to severe disease (high-certainty evidence) 7

Exception: Early convalescent plasma (within first few days) in elderly patients with mild COVID-19 may be considered, as one study showed reduced mortality (13% vs 55%) when given early versus late 1, 8. However, this does not apply to critically ill patients already requiring intensive care.

Other Pharmacologic Considerations

• Empiric antimicrobials/antibacterial agents should be used in mechanically ventilated patients with respiratory failure, with daily assessment for de-escalation based on microbiology results and clinical status 1
• Acetaminophen/paracetamol for temperature control in critically ill patients who develop fever 1
• Avoid routine use of standard intravenous immunoglobulins (IVIG) 1
• Avoid routine use of lopinavir/ritonavir 1
• Insufficient evidence for hydroxychloroquine, chloroquine, or tocilizumab as monotherapy in critically ill patients 1

Supportive Care Essentials

All COVID-19 patients require 1, 2:

• Bed rest with adequate nutritional support
• Fluid support ensuring water-electrolyte balance and internal environment stability
• Symptomatic treatments including antipyretic and analgesic therapy as needed

Common Pitfalls to Avoid

• Do not delay intubation in patients failing HFNC/NIPPV—early intubation in a controlled setting after 1-2 hours of failed trial is preferred over emergent intubation 1, 4
• Do not use high tidal volumes (>8 mL/kg)—this increases mortality in ARDS 1, 4
• Do not use staircase (incremental PEEP) recruitment maneuvers if recruitment maneuvers are employed (strong recommendation against) 1
• Do not routinely use inhaled nitric oxide in mechanically ventilated COVID-19 ARDS patients 1
• Do not give corticosteroids to mechanically ventilated patients without ARDS 1, 4
• Do not use convalescent plasma in critically ill patients—the evidence clearly demonstrates futility 1, 6, 7
• Do not administer remdesivir by any route other than IV infusion, and ensure appropriate monitoring capabilities are available 3

Monitoring Parameters

• Respiratory rate, SpO2, and work of breathing continuously or at minimum every 1-2 hours initially 9
• Arterial blood gases if clinical condition appears worse than SpO2 suggests or concern for hypercapnia 9
• Hepatic function and prothrombin time before and during remdesivir treatment 3
• Daily assessment for antimicrobial de-escalation 1
• Plateau pressures and driving pressures in mechanically ventilated patients 1, 4