Efficacy and safety of antiviral therapy in critically ill patients with mechanical ventilation: a meta-analysis with trial sequential analysis of randomized controlled trials

Abstract

Objectives: Viral reactivation is frequently detected in critically ill patients undergoing mechanical ventilation and is associated with worse outcomes. However, the efficacy and safety of antiviral therapy in these patients remain unknown. This review aims to assess the effects of antiviral therapy on mortality, viral reactivation, and adverse events in critically ill patients undergoing mechanical ventilation.

Methods: Data sources were Medline, Embase, the Cochrane Library, and reference lists. The study included randomized controlled trials that compared antiviral therapy with placebo, standard care, or no treatment. Participants were critically ill patients undergoing mechanical ventilation. Intervention was antiviral therapy. Assessment of risk of bias used the Cochrane risk of bias tool. For methods of data synthesis, risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis with trial sequential analysis.

Results: Nine trials with a broad spectrum of critically ill patients were included. No association was found between antiviral therapy and all-cause mortality at the longest follow-up (nine trials, 1790 patients, RR 0.93, 95%CI 0.79-1.11, I² 3%). Trial sequential analysis showed that the cumulative Z curve crossed the futility boundary establishing sufficient evidence. No association was also found between antiviral therapy and 28-day mortality, in-hospital mortality, 60-day mortality, or 90-day mortality. However, antiviral therapy was associated with a reduction in viral reactivation (five trials, 644 patients, RR 0.23, 95%CI 0.14-0.37, I² 0%). Trial sequential analysis showed that the cumulative Z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient evidence. Antiviral therapy was not associated with an increased risk of renal insufficiency (eight trials, 1574 patients, RR 0.88, 95%CI 0.73-1.05, I² 0%).

Conclusions: No association between antiviral therapy and mortality was found, but antiviral therapy reduced viral reactivation without increasing the risk of renal insufficiency in critically ill patients with mechanical ventilation.

Keywords: Adverse effects; Antiviral agents; Critical illness; Meta-analysis; Mortality; Trial sequential analysis; Viral reactivation.