Dexamethasone lowers mortality, ventilation use in acute respiratory disease syndrome

Treatment with intravenous (IV) dexamethasone for 10 days significantly reduces duration of mechanical ventilation at 28 days and 60-day mortality in patients with established moderate-to-severe acute respiratory disease syndrome (ARDS) compared with no dexamethasone, results of the DEXA-ARDS trial have shown.

“At the end of the study, patients treated with dexamethasone [have] more ventilator-free days—an absolute difference of 5 days,” said lead researcher Jesus Villar, from Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III in Madrid, Spain, who presented the findings at the Critical Care Reviews Meeting 2021 (eCCR21).

For all-cause mortality, “again the dexamethasone group has an absolute reduction of 15 percent mortality rate,” he added.

This DEXA-ARDS trial was conducted in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain and included patients with moderate-to-severe ARDS, defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of ≤200 mm Hg, assessed with a positive end-expiratory pressure of ≥10 cm H₂O or more and FiO₂ of ≥0.5 at 24 h after ARDS onset.

Some 277 patients were enrolled between 28 March 2013 and 31 Dec 2018, of whom 139 were randomized to the dexamethasone group and 138 to continued routine intensive care (control group). Patients in the dexamethasone group received an IV dose of 20 mg once daily from day 1 to 5, which was reduced to 10 mg from day 6 to 10. Both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial.

The data safety monitoring board stopped the trial due to the low enrolment rate after having enrolled >88 percent (277/314) of the planned sample size.

Patients in the dexamethasone group had higher mean number of ventilator-free days than those in the control group (12.3 vs 7.5 days; between-group difference, 4.8 days, 95 percent confidence interval [CI], 2.57–7.03; p<0.0001). Twenty-nine patients in the dexamethasone group and 50 in the control group had died within 60 days (21 percent vs 36 percent; between-group difference, –15.3 percent, 95 percent CI, –25.9 to –4.9; p=0.0047). [Lancet Respir Med 2020;8:267-276]

No significant between-group difference was seen in the number of adverse events. Hyperglycaemia in the ICU was the most common adverse event (105 [76 percent] in the dexamethasone group vs 97 [70 percent] in the control group), followed by new infections in the ICU (eg, pneumonia or sepsis; 33 [24 percent] vs 35 [25 percent]) and barotrauma (14 [10 percent] vs 10 [7 percent]).

“The DEXA-ARDS trial provides strong evidence that dexamethasone provides a benefit in both ventilator-free days at 28 days and in 60-day mortality for patients with moderate-to-severe ARDS,” the researchers said. [https://www.emra.org/emresident/article/critcare-alert-dexa-ards/]

“The mortality benefit found in the DEXA-ARDS trial is both large and notably similar to that seen in a meta-analysis of previous trials that used other steroids and did not necessarily use lung-protective ventilation,” they added. [J Int Care 2018;6:53]

The current study was limited by its unblinded design, discontinuation due to slow enrolment, and the exclusion of patients who had been treated already with steroids or with common comorbidities.