Is Addition of Fludrocortisone to Steroids Effective in Severe Sepsis?

LISBON — A key unresolved clinical issue regarding the use of corticosteroids in septic shock patients is whether the addition of fludrocortisone to low-dose hydrocortisone provides incremental benefit over hydrocortisone alone, Dr. Djillali Annane said at the 12th International Congress on Infectious Diseases.

“There is evidence of need for mineral corticoid supplementation in severe sepsis, and maybe what hydrocortisone provides is not enough,” observed Dr. Annane of the Versailles Saint-Quentin-en-Yvelines University, Garches, France.

Among the suggestive evidence is a recent 19-site prospective study involving 629 patients with septic shock. The prescription of corticosteroids in this observational study was at the discretion of the treating physicians. Of the total, 163 patients received low-dose hydrocortisone, 249 got hydrocortisone and fludrocortisone, and 217 received no corticosteroids.

The patients in the three study groups were of similar age and disease severity. Yet their death rates were strikingly different, with the best outcomes seen in those who were treated with hydrocortisone plus fludrocortisone. (See chart.)

The findings of this observational study led to the launch earlier this year of an ongoing, multicenter, European randomized trial with a factorial design that is looking at the benefits and risks of combination steroid therapy, compared with hydrocortisone alone, Dr. Annane said at the congress, which was sponsored by the International Society for Infectious Diseases.

Much of the interest in combination steroid therapy in septic shock stems from a French multicenter double-blind trial that Dr. Annane and colleagues reported 4 years ago. In that trial, the researchers randomized 300 adults with septic shock either to hydrocortisone IV at 200 mg/day plus a daily 50-mcg tablet of fludrocortisone, or to matching placebos. The 28-day mortality was significantly lower in the combination steroid arm (JAMA 2002;288:862–71).

Ironically, the only reason fludrocortisone was included in the corticosteroid arm was that the study ethics committee insisted upon it, even though there was little evidence at the time to support that position, he recalled.

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