Researchers saw no difference in ventilator-free days between low- and high-dose dexamethasone in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. However, their study suggests that a 10-day course of high-dose intravenous dexamethasone, compared with the recommended low dose, could improve the time required to liberate patients from a ventilator. These were among the study findings recently published in the Journal of Intensive Care Medicine.
This open-label, multicenter, randomized clinical trial in 4 intensive care units (ICUs) in Argentina enrolled 98 adult patients who: (1) had ARDS according to the Berlin Definition criteria; (2) had confirmed SARS-CoV-2 infection identified by reverse transcription polymerase chain reaction; and (3) were receiving mechanical ventilation for less than 72 hours. Prior use of dexamethasone for COVID-19 (>5 days) and terminal disease were among the exclusion criteria.
The investigators randomized 49 patients to the high-dose dexamethasone cohort, (age 63.57 ± 13.59; 26% female) and 49 patients to the control cohort (age 60.04 ± 13.08; 33% female). High-dose patients were given 16 mg dexamethasone intravenously daily for 5 days followed by 8 mg dexamethasone daily for 5 days, and low-dose patients received 6 mg dexamethasone intravenously daily for 10 days.
Researchers found ventilator-free days within 28 days of inclusion in the trial was not different between the study groups (0 [0-14] vs. 0 [0-1] days for the high- and low-dose dexamethasone groups; P= .231). Hospital and ICU mortality were also similar between groups.
Notably, this trial was prematurely terminated due to low enrollment rate. The study required 142 patients in each group to detect a difference of 3 ventilator-free days between groups, assuming a mean and a standard deviation of 9 days with a 2-sided α level of .05 and a power of 80%. The length of stay in the ICU in the high-dose dexamethasone group was 15 (9-28) days vs 24 (10-36) days for the low-dose group (P= .137), and the difference between these medians was −9 (bootstrap 95% CI, −20 to 0) days, which, due to low enrollment, according to researchers, “suggests that a 10-day course of high-dose intravenous dexamethasone improved the time required to liberate these patients from the ventilator compared with the recommend low-dose treatment.” The hospital length of stay was not affected by the treatment allocation.
Maskin LP, Bonelli I, Olarte GL, et al. High- versus low-dose dexamethasone for the treatment of COVID-19-related acute respiratory distress syndrome: a multicenter, randomized open-label clinical trial. J Intensive Care Med. Published online December 13, 2021. doi:10.1177/08850666211066799