Standard Versus Augmented Corticosteroid Dosing in Mechanically Ventilated Patients due to COVID-19

Introduction: Corticosteroids have been shown to improve outcomes in patients with acute respiratory distress syndrome (ARDS) secondary to coronavirus disease 2019 (COVID-19). However, the optimal regimen for severe COVID-19 remains unclear. This study evaluated the efficacy and safety of standard dosing (SD) dexamethasone 6 mg daily (or glucocorticoid equivalent) versus augmented dosing (AD) regimens (>6mg dexamethasone daily). We hypothesized that an AD regimen of corticosteroids would be associated with greater ventilator-free days at 28 days.


Methods: This international, multicenter, retrospective, cohort study included adult patients with PCR-confirmed COVID-19 requiring intubation and treated with corticosteroids between June 1, 2020, and June 30, 2021, at 30 medical centers. Data points were extracted electronically and via manual chart review. Inverse probability treatment weighting (IPTW) analysis was used to balance baseline characteristics. Weighted generalized linear and logistic models were used to analyze the primary, secondary, and safety outcomes.


Results: Of the 1405 patients included, 1032 (73%) received a SD regimen and 373 (27%) received an AD regimen. Unadjusted ventilator free days were significantly lower with SD compared to AD (0 [0-20]) vs 0 [0-16]; RR 0.91; 95% CI 0.84, 0.98). After IPTW adjustment, there was no significant difference in ventilator-free days at 28 days between SD and AD groups (0 [0 – 19] vs 0 [0 – 16]; aRR 0.93; 95% CI 0.86, 1.00). In addition, no significant difference was seen between SD and AD in all-cause in-hospital mortality (48.9% vs 49.3%; aOR 1.03; 95% CI 0.81, 1.30) or ICU-free days (16 [8-22] vs 16 [8-22]; aRR 0.97; 95% CI 0.88, 1.08). When safety outcomes were adjusted, patients receiving SD compared to AD experienced less hyperglycemia (72.4% vs 79.2%; aOR 1.51; 95% CI 1.13, 2.02), more gastrointestinal hemorrhage (8.2% vs 4.8%; aOR 0.54; 95% CI 0.32, 0.92), similar incidence of delirium (47.6 vs 51.2; aOR 1.14; 95% CI 0.90, 1.46), and similar rates of infection at 90 days (41.5% vs 41.6%; aOR 1.01; 95% CI 0.79, 1.28).


Conclusions: Daily corticosteroid doses greater than dexamethasone 6 mg or equivalent were not associated with reduced ventilator-free days among mechanically ventilated patients with COVID-19.