What antiviral medications are used in the ICU for patients with viral infections like influenza, COVID-19, or herpes simplex virus, especially those with impaired renal function?

Antiviral Therapy in the ICU

For critically ill ICU patients, antiviral selection depends on the specific viral pathogen: use remdesivir for COVID-19 patients requiring supplemental oxygen (but not yet mechanically ventilated), oseltamivir for severe influenza regardless of symptom duration, and acyclovir for severe HSV/VZV infections. 1, 2

COVID-19 Antiviral Management

Remdesivir is the only antiviral with proven benefit in critically ill COVID-19 patients, but only for those requiring supplemental oxygen who are not yet on invasive mechanical ventilation. 1, 2

• Dosing regimen: 200 mg IV loading dose on day 1, followed by 100 mg IV daily for 5 days 1, 3
• Clinical benefit: Remdesivir provides modest clinical improvement and reduces risk of clinical worsening within 28 days, but makes little or no difference to mortality 1, 4
• Critical limitation: 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

Renal Impairment Considerations for Remdesivir

No dosage adjustment is required for remdesivir in patients with any degree of renal impairment, including those on dialysis. 3

• Exposures of remdesivir metabolites (GS-441524 and GS-704277) and the excipient SBECD are increased in patients with renal impairment, but safety data from Study GS-US-540-5912 (163 subjects with renal impairment including those on dialysis) support use without dose adjustment 3
• Monitor hepatic transaminases, bilirubin, and eGFR during therapy 2

Antivirals to AVOID in COVID-19

Do not use lopinavir/ritonavir for COVID-19, as the Surviving Sepsis Campaign specifically recommends against its routine use based on trial data showing no benefit. 5, 4

• Trial data showed no significant difference in time to clinical improvement, viral load reduction, or 28-day mortality compared to standard care 5
• Do not use oseltamivir for COVID-19, as it has no activity against coronaviruses 4
• Do not use Paxlovid (nirmatrelvir/ritonavir) for critically ill ICU patients with COVID-19 4
• Insufficient evidence exists for other antiviral agents including chloroquine, hydroxychloroquine, interferons, and tocilizumab 5

Influenza Antiviral Management

Initiate oseltamivir immediately for suspected or confirmed severe influenza in ICU patients, regardless of symptom duration or time since symptom onset. 1, 2

• Standard dosing: 75 mg PO twice daily for 5 days 1
• Timing is critical: Antiviral effectiveness decreases significantly after 48-72 hours of symptom onset, but treatment should still be initiated in critically ill patients even beyond this window 2
• Renal dose adjustment required: Monitor renal function and adjust dose accordingly 2
• Monitor for neuropsychiatric effects: Including delirium and abnormal behavior, particularly in pediatric patients 1, 2

Pharmacokinetic Challenges in Critical Illness

Limited data on oseltamivir pharmacokinetics is available in critically ill patients, and absorption may be impaired in those with gastrointestinal dysfunction 6

• Consider higher loading doses of hydrophilic antimicrobials in critically ill patients due to increased volume of distribution from the dilution effect 1
• Therapeutic drug monitoring should be considered to overcome suboptimal drug exposure during early therapy 1

Resistance Concerns

The selection of A(H1N1)pdm09 resistant variants to oseltamivir is particularly problematic in critically ill patients hospitalized in ICUs 6

Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV)

Acyclovir is the first-line agent for severe HSV and VZV infections in critically ill patients. 1, 2

• Monitor renal function, neurologic toxicity, and weekly CBC during therapy 2
• Acyclovir is safe for disseminated HSV/VZV in pregnancy 1, 2

Cytomegalovirus (CMV)

Ganciclovir or foscarnet should be used for CMV viremia in high-risk populations, such as transplant recipients or patients with severe immunosuppression. 1, 2

• Longer antiviral courses and CMV surveillance are recommended in immunocompromised patients (hematologic malignancies, transplant recipients) 2

Co-Infection Management and Antimicrobial Stewardship

Do not routinely add empirical antibiotics with antivirals unless the patient is critically ill with septic shock, mechanically ventilated, or has procalcitonin >0.5 ng/mL with clinical deterioration. 2

• Co-infection rates with influenza in COVID-19 patients are low (approximately 4-5%) 4
• Rapidly de-escalate empirical anti-influenza therapy based on negative testing and clinical response 4
• Obtain comprehensive microbiologic workup before starting empirical antibiotics to facilitate early de-escalation 2
• If empiric antimicrobials are initiated, assess for de-escalation daily and re-evaluate duration and spectrum based on microbiology results and clinical status 5

Special Populations

Oseltamivir is safe for severe influenza in pregnancy, and acyclovir is safe for disseminated HSV/VZV in pregnancy. 1, 2

• In geriatric patients (≥65 years), no dosage adjustment is required for remdesivir, but exercise appropriate caution given greater frequency of decreased hepatic, renal, or cardiac function 3

Critical Pitfalls to Avoid

• Never use oseltamivir for COVID-19 - it has no activity against coronaviruses 4
• Never continue remdesivir after progression to mechanical ventilation - no benefit demonstrated 1, 4
• Never use lopinavir/ritonavir for COVID-19 - trial data shows no benefit and it is specifically recommended against 5, 4
• Never delay oseltamivir for severe influenza - initiate immediately regardless of symptom duration 1, 2