Dexamethasone Recommended for Mechanically Ventilated COVID-19 Patients

July 1, 2020

Dexamethasone should also be used for up to 10 days in patients with COVID-19 who require supplemental oxygen but are not mechanically ventilated.

The COVID-19 Treatment Guidelines Panel recommends using dexamethasone in patients with coronavirus disease 2019 (COVID-19) who are mechanically ventilated.

The Panel also suggested the drug be used at a dose of 6 mg per day for up to 10 days in patients with COVID-19 who required supplemental oxygen but who were not mechanically ventilated. However, they suggested dexamethasone not be used in patients with COVID-19 who did not require supplemental oxygen.

The recommendations were based on the findings of a preliminary, unpublished analysis from a large, multicenter, randomized, open-label trial for hospitalized patients in the United Kingdom demonstrated patients who were randomized to receive dexamethasone had a reduced rate of mortality compared to those who received standard of care. The benefit was greatest in patients who required mechanical ventilation at the time of enrollment. There was no benefit among patients who did not require supplemental oxygen at enrollment.

In the Randomised Evaluation of COVID-19 Therapy (RECOVERY) study sponsored by the National Health Service, hospitalized patients with clinically suspected or laboratory-confirmed COVID-19 were randomized to receive 1 of several potential treatments. One study arm was administered dexamethasone 6 mg daily either orally or intravenously for 10 days.

Investigators performed an initial analysis on 6425 participants—2104 participants in the dexamethasone group and 4321 in the control arm. The mean age was 66.1 years old, 64% were male, and 56% had at least 1 major comorbidity. At baseline, 16% of the participants needed invasive mechanical ventilation, 60% received supplemental oxygen but no invasive ventilation and 24% did not need oxygen supplementation.

The primary endpoint of the study was 28-day mortality. Among those included, 21.6% of participants in the dexamethasone cohort and 24.6% of those in the control arm died with 28 days of enrollment (age-adjusted rate ratio [RR], .83; CI, .74-.92; P <.001). There was a significant interaction between baseline severity of COVID-19 and the effect of dexamethasone.

For patients in the dexamethasone group who required invasive mechanical ventilation, there was a greater survival benefit: 29% of such participants died within 28 days of study enrollment compared with 40.7% in the control arm (RR, .65; 95% CI, .51-.82; P <.001). Of the dexamethasone-treated patients, 21.5% who required supplemental oxygen at enrollment died within 28 days compared with 25% in the control arm (RR, 1.22; 95% CI, .93-1.61; P=.14).

Respiratory support status varied by age at the time of randomization. Those who received mechanical ventilation were more likely to be less than 70 years old. For the patients who were older than 80 years old, only 1% were mechanically ventilated, while 62% were in the oxygen group and 37% were in the no oxygen group. Due to this, the survival benefit of dexamethasone for mechanically ventilated patients who were older than 80 years remained unclear.

Although the full analysis of the study is still ongoing and the results have not yet been published in a peer-reviewed journal, investigators are still looking to find the results of other key endpoints, potential adverse events, and the efficacy of dexamethasone.


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