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Higher dexamethasone dose of no benefit in critically ill COVID-19 patients

Rod Tucker
28 October, 2021  

Doubling the dose of dexamethasone dose in COVID-19 patients hospitalised with severe hypoxia had no effect on 28-day mortality.

Increasing the dexamethasone dose from 6 mg to 12 mg/day in hospitalised patients with COVID-19 and severe hypoxia, has no effect on overall mortality. This was the conclusion of a randomised trial undertaken by researchers from the COVID STEROID 2 Trial group, Department of Intensive Care, Rigshospitalet, Copenhagen, Denmark. The value of dexamethasone in hospitalised patients with COVID-19 was shown in an open-label trial published in February 2021, which found that dexamethasone 6mg/daily for 10 days, resulted in a lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen. Guidance from the World Health Organisation also recommends a dexamethasone dose of 6 mg/daily either orally or intravenously.

Whether a higher dexamethasone dose would be more beneficial to those with severe COVID-19 is uncertain. However, some evidence suggests that in patients with acute respiratory distress syndrome (which can be induced by infection with the virus) initial dexamethasone doses of 20 mg for five days, could reduce the duration of mechanical ventilation and overall mortality. Thus, the purpose of the COVID STEROID 2 trial was to evaluate the efficacy and safety of a higher dose of dexamethasone in hospitalised adult patients with COVID-19 and severe hypoxia. The researcher’s working hypothesis was that a higher dexamethasone dose would increase the number of days alive without life support. The study was conducted at 26 hospitals in four countries and included patients who required supplemental oxygen, and both non-invasive and invasive mechanical ventilation. Participants were randomised 1:1 to receive either 6 or 12 mg of dexamethasone daily as a bolus injection for up to 10 days after randomisation. Patients were assessed after 28 days with the primary outcome set as the number of days alive without life support (i.e., invasive mechanical ventilation, circulatory support or kidney replacement therapy) after 28 days. There were several secondary outcomes, including the number of days alive without life support at 90 days.

Findings

A total of 982 randomised patients were included in the final analysis with a median age of 65 years (31% female). The most common co-morbidities were diabetes (27% in the 12 mg dexamethasone group, 34% in the 6 mg group) and ischaemic heart disease or heart failure (14% in both groups). After 28 days, the median number of days alive without life support was 22 days in those with a dexamethasone dose of 12 mg and 20.5 days in the dexamethasone 6 mg group (adjusted mean difference, aMD  = 1.3 days, p = 0.07). The 28-day mortality was 27.1% and 32.3% (dexamethasone 12 mg vs 6 mg). Similarly after 90 days the corresponding number of days was 84 and 80 days (dexamethasone 12 mg vs 6 mg) and this difference was not statistically significant.

The authors concluded that doubling the dexamethasone dose did not improve the number of days alive but suggested that they trial might have been underpowered to identify a significant difference.

Citation

The COVID STEROID 2 Trial Group. Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomised Trial. JAMA 2021