Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study

What is already known on this topic Dexamethasone decreased day-28 mortality in the randomised controlled trial RECOVERY in patients admitted for COVID-19, including 74% who required oxygen and 16% invasive mechanical ventilation (iMV). Other trials targeting critically ill patients did not replicate this finding, leaving uncertainty about the benefits of dexamethasone. What this study adds In our large observational cohort of critically ill COVID-19 patients, of whom 61% required iMV, early systemic dexamethasone was not associated with lower day-28 mortality compared to no steroids. However, early dexamethasone was associated with less need for iMV, more days alive and off iMV, and a higher frequency of ventilator-associated pneumonia in the iMV sub-group. How this study might affect research, practice, or policy This study suggests that early dexamethasone may be warranted in critically ill COVID-19 patients, provided those receiving iMV are monitored closely for ventilatory-associated pneumonia.

Background

Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19

Methods

We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events

Results

Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively; P  = 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio [aHR], 1.06; 1.04–1.09; P  < 0.001), worse SOFA score (aHR, 1.13; 1.06–1.20; P  < 0.001), and immunocompromised status (aHR, 1.59; 1.01–2.50; P  = 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%, P  < 0.001) and more ventilator-free days by day 28 (22 [2–28] vs. 17 [1–28] days, P  = 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 [1.01–1.63], P  = 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding

Conclusions

Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.