Dual Steroid Treatment Adds Benefit in Septic Shock, Study Finds


Researchers found a significant decrease in mortality or discharge to hospice with the hydrocortisone-fludrocortisone combination versus hydrocortisone alone in septic shock cases.

Initiation of two steroids (hydrocortisone and fludrocortisone) in patients with septic shock is associated with lower rates of death and discharge to hospice compared to hydrocortisone alone, according to the findings of a recent analysis.

Sepsis is a life-threatening inflammatory condition caused by the body’s response to a widespread infection. Severe cases of sepsis that require certain medications to manage dangerously low blood pressure are classified as septic shock. In these instances, estimated rates of patient fatality are higher than 30% in U.S. hospitals.

To combat widespread inflammation in septic shock, international guidelines suggest initiating steroid therapy, specifically hydrocortisone. Hydrocortisone is sometimes paired with another steroid, fludrocortisone. Combination therapy is not reflected in septic shock guidelines, however, and the benefit is unclear.

Researchers from Boston University and the University of Toronto sought to better understand the role of combination therapy in septic shock treatment.

“We used target trial emulation and a large retrospective multicenter database to compare the use of hydrocortisone alone to hydrocortisone and fludrocortisone in patients with septic shock,” lead author Nicholas Bosch, M.D., M.Sc., assistant professor at the Boston University Chobanian & Avedisian School of Medicine, told Formulary Watch.

The team analyzed 88,275 septic shock patients from 2016 to 2020, comparing those who received hydrocortisone-fludrocortisone treatment to those who received hydrocortisone alone. The two cohorts were compared on the primary outcome, which was patient death or a discharge to hospice.

“We found a significant ~3 % decrease in mortality or discharge to hospice with the use of combination hydrocortisone-fludrocortisone versus hydrocortisone alone,” Bosch explained. In addition, patients receiving combination hydrocortisone-fludrocortisone experienced significantly fewer days in the hospital than those on hydrocortisone alone.

Reassuringly, there was no significant differences in the safety profile of either regimen, suggesting that adding a second steroid did not present additional or more severe side effects.

While future randomized trials comparing dual and monotherapy corticosteroids for septic shock would be helpful to confirm the difference in outcomes, this study highlights the potential benefits and low risks associated with the hydrocortisone-fludrocortisone combination.

“In the context of existing evidence and the results from our study, it is reasonable to add fludrocortisone to hydrocortisone in patients with septic shock in whom clinicians plan to start corticosteroids,” Bosch said.

The study was published in JAMA Internal Medicine and was funded by the National Institute of Health.

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