What antiviral medications, such as oseltamivir (generic name) or remdesivir (generic name), are recommended for critically ill patients with viral infections, such as influenza or COVID-19, in the Intensive Care Unit (ICU)?

Antiviral Therapy in the ICU

COVID-19: Remdesivir for Severe Disease

For critically ill patients with severe COVID-19 requiring supplemental oxygen but not yet on invasive mechanical ventilation, remdesivir is the recommended antiviral agent, administered as 200 mg IV loading dose on day 1 followed by 100 mg IV daily for 5 days. 1

Patient Selection Criteria

• Severe COVID-19 is defined as hospitalized patients with respiratory rate >30 breaths/min, respiratory distress, SpO2 <94% on room air, or need for supplemental oxygen 1
• The WHO provides a weak/conditional recommendation for remdesivir in this population, emphasizing modest benefits on clinical improvement and reduction in need for invasive mechanical ventilation 1

Critical Limitation

• Do not use remdesivir in patients already requiring invasive mechanical ventilation or ECMO, as the WHO suggests against its use in this subgroup due to lack of benefit on survival or other patient-important outcomes 1
• This is a crucial distinction: remdesivir may help prevent progression to mechanical ventilation but does not benefit those already intubated 1

Contraindications and Monitoring

• Contraindicated in severe hepatic impairment or ALT ≥5 times upper limit of normal 1
• Monitor for hyperglycemia, liver dysfunction, and renal failure 1
• Treatment duration extends to 10 days only if patient progresses to requiring invasive mechanical ventilation/ECMO during the initial 5-day course 1

Evidence Quality

• Remdesivir probably makes little or no difference to mortality but increases chance of clinical improvement slightly and decreases risk of clinical worsening within 28 days 1
• The Surviving Sepsis Campaign found insufficient evidence to recommend other antiviral agents (including lopinavir/ritonavir) in critically ill COVID-19 patients, and specifically suggests against routine use of lopinavir/ritonavir 2

COVID-19: Paxlovid Not for ICU Patients

Paxlovid (nirmatrelvir/ritonavir) is NOT recommended for critically ill ICU patients with COVID-19. 3

• Paxlovid is indicated only for outpatients or those with mild-to-moderate COVID-19 at high risk for progression, when treatment can be initiated within 5 days of symptom onset 1, 3
• Guidelines explicitly state Paxlovid should not be prescribed for patients hospitalized primarily for COVID-19 3
• The drug's role is prevention of hospitalization, not treatment of established severe disease 3

Influenza: Oseltamivir Remains Standard

For critically ill patients with confirmed or suspected influenza, oseltamivir 75 mg PO/NG twice daily should be initiated immediately, even if >48 hours from symptom onset. 4

Dosing and Administration

• Standard dose: 75 mg twice daily for 5 days 5
• Renal dose adjustments required: For CrCl 30-60 mL/min, reduce to 30 mg twice daily; for CrCl 10-30 mL/min, reduce to 30 mg once daily 5
• Can be administered via nasogastric tube in intubated patients 5

Evidence in Critical Illness

• While efficacy in critically ill patients is based on observational studies rather than RCTs, oseltamivir remains the standard of care 4
• Early initiation is associated with reduced mortality in severe influenza, even when started >48 hours after symptom onset 4
• Pharmacokinetic concerns exist in critically ill patients, with limited data on drug absorption and bioavailability in this population 4

Resistance Monitoring

• Selection of A(H1N1)pdm09 resistant variants to oseltamivir is particularly problematic in ICU patients 4
• Consider alternative neuraminidase inhibitors (peramivir, zanamivir) if resistance suspected, though data in critically ill patients are scarce 4

Alternative Neuraminidase Inhibitors

• Peramivir (IV formulation) may be considered when enteral administration is not feasible, though evidence in critically ill patients is limited 4
• Zanamivir (inhaled) has minimal data in mechanically ventilated patients and is generally not recommended in ICU settings 4

Common Pitfalls to Avoid

COVID-19 Specific

• Do not use oseltamivir for COVID-19: Multiple early pandemic guidelines explicitly recommended against oseltamivir for SARS-CoV-2, as it has no activity against coronaviruses 2
• Do not continue remdesivir in patients who progress to mechanical ventilation beyond the initial treatment course, as no benefit has been demonstrated 1
• Avoid lopinavir/ritonavir: The Surviving Sepsis Campaign suggests against its routine use based on trial data showing no benefit 2

Influenza Specific

• Do not withhold oseltamivir based on time from symptom onset in critically ill patients—benefit has been observed even with delayed initiation 4
• Do not assume adequate absorption of enteral oseltamivir in patients with shock, ileus, or requiring vasopressors—pharmacokinetic data are limited 4

Co-infection Considerations

• Empirical oseltamivir was commonly given during early COVID-19 pandemic because laboratory diagnosis takes time, but co-infection rates with influenza in COVID-19 patients are low (approximately 4-5%) 2
• Rapidly de-escalate empirical anti-influenza therapy based on negative testing and clinical response 2