Abstract Rationale There is increasing evidence for the beneficial impact of dexamethasone administration for acute respiratory distress syndrome (ARDS), which may augment endogenous glucocorticoid production and blunt the dysregulated inflammatory response in ARDS. Prior research demonstrates that both endogenous glucocorticoid production and host inflammatory markers vary based on an innate circadian rhythm, and studies of other disease states suggest that the dose-timing of medications or vaccines modulates their efficacy. We hypothesized that the dose-timing of dexamethasone for ARDS might be associated with the drug’s relationship with mortality. Methods We used electronic medical record data from the Emory Healthcare system to identify a cohort of patients who received mechanical ventilation between October 1, 2022 to February 28, 2025. We included adult patients who had a minimum arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FIO2 P/F ratio) = 200 while on mechanical ventilation (IMV) and who received intravenous dexamethasone within 24 hours of IMV initiation. Our primary exposure of interest was dexamethasone dose-timing, which was defined as morning (07:00 Eastern Time) versus evening (19:00 Eastern Time) dose-timing based on minimizing the difference between the observed and above dose-times. We regressed dose-time on in-hospital mortality with the following covariates: Covid-19 status, non-respiratory SOFA score, BMI, race, sex, and age. Results Our cohort included 482 patients who were 37.3% White, 51.0% male, and who had a mean age of 58 years. Eighty (16.6%) of patients were Covid-19 positive and 129 (26.8%) of patients died during the hospitalization. 273 (59.6%) of patients were assigned to the morning group. Mean mortality varied throughout by hour of dexamethasone administration, with patients receiving dexamethasone from midnight to 04:00 or from 16:00 to 20:00 having lower mortality (Figure 1). In adjusted analysis, dexamethasone dose-time was not associated with mortality (OR 0.84, CI 0.40-1.73). Conclusions Dose-timing of dexamethasone was not associated with mortality when modeled as a dichotomous variable intended to reflect time from peak cortisol. Further research is needed to determine the ideal dexamethasone administration-time and if additional patient factors or biomarkers could be used to personalize dexamethasone treatment for ARDS. This abstract is funded by: Supported by the Stimulating Access to Research in Residency of the National Institutes of Health under Award Number R38AI174306
Rzewnicki et al. (Fri,) studied this question.