Antiviral Therapy in the ICU for Critical Care Medicine
Primary Recommendation
For critically ill ICU patients with viral infections, remdesivir is the only antiviral with proven benefit in severe COVID-19 requiring supplemental oxygen but not yet on invasive mechanical ventilation (200 mg IV loading dose day 1, then 100 mg IV daily for 5 days), while oseltamivir should be initiated for suspected or confirmed severe influenza regardless of symptom duration. 1, 2, 3
COVID-19 Antiviral Management
Remdesivir Indications and Dosing
Administer remdesivir to critically ill COVID-19 patients requiring supplemental oxygen but NOT yet on invasive mechanical ventilation: 200 mg IV loading dose on day 1, followed by 100 mg IV daily for 5 days 1, 2, 4
Do NOT continue remdesivir in patients who progress to invasive mechanical ventilation beyond the initial treatment course, as no survival benefit has been demonstrated in this subgroup 1, 4
Remdesivir provides modest clinical improvement and reduces risk of clinical worsening within 28 days, but makes little or no difference to mortality 1, 4
Contraindications and Monitoring
Contraindicated in severe hepatic impairment or ALT ≥5 times upper limit of normal 4
Monitor hepatic transaminases, bilirubin, and eGFR during therapy 2
Potential adverse events include hyperglycemia, liver dysfunction, and renal failure 4
Renal Dose Adjustments
In critically ill patients with renal impairment, pharmacokinetic alterations are significant and must be considered 5
Standard remdesivir dosing does not require renal adjustment, but monitor closely for adverse effects 2
Influenza Antiviral Management
Oseltamivir Dosing
Initiate neuraminidase inhibitors (oseltamivir or zanamivir) immediately for suspected or confirmed severe influenza, regardless of symptom duration 2, 3
Standard adult dosing: 75 mg PO twice daily for 5 days 3
Pediatric dosing (1-12 years): Weight-based dosing from 30-75 mg twice daily for 5 days 3
Renal Adjustments for Oseltamivir
Critical renal dosing adjustments are essential 3:
- Moderate impairment (CrCl 30-60 mL/min): 30 mg twice daily for 5 days
- Severe impairment (CrCl 10-30 mL/min): 30 mg once daily for 5 days
- ESRD on hemodialysis: 30 mg immediately, then 30 mg after every hemodialysis cycle (max 5 days)
- ESRD on CAPD: Single 30 mg dose immediately
Monitoring
Monitor for neuropsychiatric effects including delirium and abnormal behavior, particularly in pediatric patients 3
Renal dose adjustment and monitoring are critical as renal clearance exceeds glomerular filtration rate 3
Other Viral Infections in the ICU
Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV)
Acyclovir is first-line for severe HSV and VZV infections in critically ill patients 2
Monitor renal function, neurologic toxicity, and weekly CBC during therapy 2
Cytomegalovirus (CMV)
Ganciclovir or foscarnet for CMV viremia in high-risk populations (transplant recipients, severe immunosuppression) 2
Longer antiviral courses and CMV surveillance recommended in immunocompromised patients 2
Critical Pitfalls to Avoid
What NOT to Use
Do NOT use lopinavir/ritonavir for COVID-19 - trial data shows no benefit and it is specifically recommended against 5, 1, 2
Do NOT use oseltamivir for COVID-19 - it has no activity against coronaviruses 1
Do NOT use Paxlovid (nirmatrelvir/ritonavir) in critically ill ICU patients with COVID-19 1
Avoid hydroxychloroquine - limited benefit with significant cardiac toxicity (QT prolongation, ventricular tachycardia) especially when combined with azithromycin 5
Timing Considerations
Initiate antiviral therapy early - effectiveness decreases significantly after 48-72 hours of symptom onset for influenza 2
Antiviral timing is critical for effectiveness in all viral infections 2
Antimicrobial Stewardship in Viral Infections
Co-infection Management
Co-infection rates with influenza in COVID-19 patients are low (4-5%) 1
Rapidly de-escalate empirical anti-influenza therapy based on negative testing and clinical response 1
Do NOT routinely add empirical antibiotics with antivirals unless: critically ill with septic shock, mechanically ventilated, or procalcitonin >0.5 ng/mL with clinical deterioration 2
Bacterial Co-infection in Influenza
Bacterial secondary infection occurs in 20% of severe influenza cases 6
Streptococcus pneumoniae and Staphylococcus aureus remain the prevalent pathogens 6
If antimicrobial treatment is considered, beta-lactam providing coverage for S. pneumoniae ± MSSA should be first option (amoxicillin-clavulanate or third-generation cephalosporins) 5
Pharmacokinetic Considerations in Critical Illness
Altered Drug Handling
In critically ill patients, higher than standard loading doses of hydrophilic antimicrobials may be needed due to increased volume of distribution from the dilution effect, independent of renal function 5
Drug pharmacokinetics are significantly altered in critically ill patients due to sepsis pathophysiology 5
Tissue hypoperfusion from shock and/or vasoconstrictors may modify tissue pharmacokinetics, causing extended time to reach equilibrium between plasma and tissue compartments 5
Therapeutic Drug Monitoring
Consider therapeutic drug monitoring (TDM) for anti-infective agents in critically ill patients to overcome suboptimal drug exposure during early therapy 7
TDM may assist in optimizing treatment outcomes, particularly for drugs with narrow therapeutic windows 7
Special Populations
Pregnancy
Oseltamivir is safe for severe influenza in pregnancy 2
Acyclovir is safe for disseminated HSV/VZV in pregnancy 2