2025 Southeastern Residency Conference

Title: Dexamethasone versus dexamethasone and fludrocortisone in patients with septic shock and acute respiratory distress syndrome


Authors: Gabrielle Cromley, PharmD; Audrey Johnson, PharmD, BCCCP; Eric K. Shaw PhD; Stephanie Lesslie, PharmD, BCPS, BCCCP


Objective: The purpose of this study was to compare duration of vasopressors within 30 days in patients with septic shock and ARDS who received either dexamethasone or dexamethasone and fludrocortisone.


Self Assessment Question: By what mechanism does mineralocorticoid activity improve septic shock?


Background:
Corticosteroids are recommended for both septic shock and moderate to severe acute respiratory distress syndrome (ARDS). Hydrocortisone is recommended in septic shock requiring vasopressors and it has both glucocorticoid and mineralocorticoid effects. Its mineralocorticoid effect provides additional benefit in septic shock by increasing fluid retention and peripheral vascular resistance. Dexamethasone is recommended for ARDS given the findings of the DEXA-ARDS trial which showed decreased duration of mechanical ventilation and all-cause mortality. Dexamethasone exhibits pure glucocorticoid activity and does not have mineralocorticoid activity. For patients with septic shock and ARDS, the ideal corticosteroid regimen is not clearly defined. The addition of fludrocortisone to dexamethasone may be beneficial in these patients given its mineralocorticoid effects. The purpose of this study is to determine if the addition of fludrocortisone to dexamethasone reduces vasopressor duration in patients with septic shock and ARDS.
 
Methodology: 
This single-center, retrospective cohort study was conducted at a 711-bed academic medical center. All data was collected from electronic medical records (EMR) by individual chart review. EMR reports of dexamethasone and fludrocortisone administrations between May 2020 through September 2024 were generated. Mechanically ventilated adult patients were included if they met all of the following criteria: PaO₂:FiO₂ < 200; receiving antibiotic therapy; requiring vasopressor support ≥ 10 mcg/min norepinephrine equivalent; administration of dexamethasone for ARDS with or without fludrocortisone for ≥ 48 hours. Patients were excluded if they met any of the following criteria: cardiogenic shock, chronic corticosteroid use, brain death, pregnant, or incarcerated. Patients who received concomitant fludrocortisone and dexamethasone were excluded if fludrocortisone was initiated > 5 days after starting dexamethasone. The primary outcome was the duration of vasopressors within 30 days. Secondary outcomes included all-cause mortality, ICU mortality, duration of mechanical ventilation in ICU survivors, ICU length of stay, and cumulative norepinephrine equivalent (NEE) dose, and fluid balance.
 
Results:
Twenty-nine patients were included in the dexamethasone only group and 15 patients were included in the dexamethasone/fludrocortisone group. Median duration of vasopressors within 30 days was 5 days (IQR 3.5 – 13) in dexamethasone/fludrocortisone group and 5 days (IQR 3 – 10) in the dexamethasone only group (p = 0.81). All-cause mortality was similar with 10 (66.%7) in the dexamethasone/fludrocortisone group and 18 (62.1%) in the dexamethasone only group (p = 0.76). ICU mortality was also similar with 9 (60%) in the dexamethasone/fludrocortisone group and 18 (62.1%) in the dexamethasone only group (p = 0.89). Median ICU length of stay was 11 days (IQR 8.5 – 26.5) for dexamethasone/fludrocortisone versus 12 days (IQR 8 – 21) in the dexamethasone only group (p = 0.84). Median duration of mechanical ventilation was 5 days (IQR 4 – 8) in the dexamethasone/fludrocortisone group compared to 7 days (IQR 6 – 12) in the dexamethasone only group (p = 1.0). The dexamethasone/fludrocortisone group required a median of 55,684 mcg NEE (IQR 36,132 – 86,663) cumulatively compared to 41,651 mcg NEE (IQR 13,686 – 62,784) with dexamethasone only (p = 1.0). Median difference in fluid balance after corticosteroids was +1.9 L (IQR -2.8 – 6.5) in the dexamethasone/fludrocortisone group and +0.54 L (IQR -2.6 – 4.9) in the dexamethasone only group (p = 1.0).
 
Conclusion: 
Patients with septic shock and ARDS had similar duration of vasopressors within 30 days whether they received dexamethasone/fludrocortisone or dexamethasone alone. There were no differences in all-cause mortality, ICU mortality, or ICU length of stay between groups. Patients who received dexamethasone/fludrocortisone had numerically shorter duration of mechanical ventilation and more positive fluid balance but these findings were not statistically significant. This study was underpowered and limited by its small sample size. Larger randomized controlled trials are needed to investigate the effects of fludrocortisone and dexamethasone in patients with ARDS and septic shock.


Resident contact: garbrielle.cromley@hcahealthcare.com