Mineralocorticoid magic? Evaluating fludrocortisone in septic shock

The use of adjunctive steroids for septic shock has been controversial since the turn of the century. The largest clinical trial evaluating adjunctive corticosteroids in septic shock failed to report a mortality benefit while comparing a continuous intravenous hydrocortisone infusion to placebo despite shortening the time to shock resolution. Alternatively, two clinical trials evaluating a combination of intravenous hydrocortisone and enteral fludrocortisone in septic shock reported a mortality benefit. Robust data on the outcomes associated with the addition of fludrocortisone to hydrocortisone compared to hydrocortisone alone are sparse. Likewise, significant practice variation exists regarding the prescription of steroids for septic shock. For this manuscript, we completed a comprehensive search of the utility of the combination of fludrocortisone and hydrocortisone for the management of septic shock. The purpose of the review is to explore the pharmacology, pharmacokinetics and pharmacodynamics of fludrocortisone and to evaluate the present literature to aid clinicians in making personalized treatment decisions for this controversial topic.