July 5, 2022
High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure.
What was the research question?
Does high-dose dexamethasone after 60-day all-cause mortality compared to standard dose in patients with severe COVID-19 pneumonia and acute hypoxemic respiratory failure?
Dose respiratory support using High Flow Nasal Oxygen (HFNO2) or Continuous Positive Airway Pressure (CPAP) affect the occurrence of invasive mechanical ventilation compared to oxygen support standard of care therapy (O2sc) in patients with severe COVID-19 pneumonia and acute hypoxemic respiratory failure?
How did they do it?
A multicenter, placebo-controlled randomized clinical trial at 19 ICUs in France with a 2 × 3 factorial randomization design for dexamethasone and oxygenation strategies.
Total of 841 patients with severe COVID-19 infection and hypoxemic respiratory failure (PO2<70 mm Hg, O2 Sat <90 on room air, respiratory distress, RR >30 breaths/min, labored breathing) were included in the study.
546 were randomized to receive high-dose dexamethasone at 20 mg at day 1-5, then 10 mg at day 6-10 (270 patients), or standard dexamethasone at 6 mg daily (or placebo prior to RECEVERY trial) for 10 days (276 patients). The primary outcome was 60-day all-cause mortality.
333 patients who were not already on invasive mechanical ventilation (IMV), were randomized to receive O2sc therapy (109 patients including 56 patients on standard dexamethasone), CPAP (109 patients including 57 on standard dexamethasone), or HFNO2nasal oxygen (114 patients including 56 on standard dexamethasone). The primary outcome was cummime to invasive mechanical ventilation requirement.
What did they find?
60-day mortality was not significantly different in the high-dose dexamethasone group compared to the standard dexamethasone group (HR 0.96 [95% CI, 0.69-1.33]; P= 0.79).
Cumulative incidence of IMV at day 28 was not significantly different in the O2sc group compared to CPAP (HR 1.08[95% CI, 0.71-1.63]); or HFNO2 (HR 1.04 [95% CI, 0.69-1.55]).
60-day mortality was not significantly different in the O2sc group compared to CPAP (HR, 0.97 [95% CI, 0.58-1.61]); or HFNO2 (HR 0.89 [95% CI, 0.53-1.47]).
Are there any limitations?
17% lack of adherence to allocated oxygen therapy.
58 patients fulfilled criteria for intubation but were not intubated.
Lower experience with CPAP in some center.
Awake proning was not standardized or recorded.
Underpowered for 8% difference in intubation rate as per RECOVERY-RS trial).
What does it mean?
In patients with COVID-19 infection and acute hypoxemic respiratory failure, high dose dexamethasone therapy did not significantly alter 60-day mortality and different respiratory support strategy did not affect 28-day requirement for invasive mechanical ventilation.
Continue to use dexamethasone at 6 mg daily dose in COVID patients with hypoxemia and utilize the oxygen support strategy that is most comfortable for the patient.