Is hydrocortisone and fludrocortisone (Flu Cortizone) more effective than hydrocortisone alone in patients with septic shock?

From the Guidelines

Hydrocortisone alone is the recommended treatment for septic shock, not hydrocortisone with fludrocortisone (which I assume is what "flu Cortizone" refers to). For patients with septic shock, intravenous hydrocortisone at a dose of 200-300 mg per day, typically divided into 3-4 doses or given as a continuous infusion for 5-7 days or until vasopressor support is no longer needed, is the standard approach. Adding fludrocortisone to hydrocortisone does not provide additional benefit in most septic shock cases and is not routinely recommended. The rationale is that hydrocortisone alone at these doses provides sufficient glucocorticoid and mineralocorticoid effects to help restore vascular tone, increase blood pressure, and potentially improve responsiveness to vasopressors in septic shock. While some older studies suggested a potential benefit of combination therapy, more recent evidence indicates that hydrocortisone monotherapy is equally effective and simpler to administer, as suggested by the guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients 1.

Some key points to consider when treating septic shock with hydrocortisone include:

• The dose of hydrocortisone should be less than 400 mg per day, as higher doses do not provide additional benefits and may increase the risk of adverse effects 1
• Hydrocortisone should be administered for at least 3 days at the full dose, or longer in adult patients with septic shock that is not responsive to fluid and moderate to high-dose vasopressor therapy 1
• The use of fludrocortisone in combination with hydrocortisone is not recommended, as it does not provide additional benefits and may increase the risk of adverse effects 1
• Treatment should be initiated early in patients with septic shock who remain hypotensive despite adequate fluid resuscitation and vasopressor therapy, as suggested by the surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016 1.

Overall, the current evidence suggests that hydrocortisone alone is the preferred treatment for septic shock, and that combination therapy with fludrocortisone is not necessary.

From the Research

Comparison of Hydrocortisone and Fludrocortisone vs Hydrocortisone Alone

• The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain 2.
• A systematic review and network meta-analysis of randomized controlled trials found that fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence) 2.
• Another study found that the 28-day mortality rate was reduced after dual corticosteroid treatment with hydrocortisone and fludrocortisone (risk ratio, 0.88; 95% confidence intervals [CI], 0.78-0.99) 3.
• However, a retrospective observational study found that patients who received hydrocortisone had higher hospital mortality (52% vs 38%; P < .01) compared to those who did not receive hydrocortisone, although the study noted that patients who received hydrocortisone were more severely ill than those who did not 4.

Efficacy of Hydrocortisone Therapy

• A multicenter, randomized, double-blind, placebo-controlled trial found that hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed 5.
• The use of stress dose corticosteroids, specifically hydrocortisone, in septic shock is heterogeneous, and current clinical trials yield conflicting results 4.

Clinical Utilization of Corticosteroids

• The care of patients with worsening septic shock involves multiple treatment decisions involving vasopressor choices and adjunctive treatments, including corticosteroids 6.
• A systematic review and meta-analysis found that patients who underwent dual corticosteroid treatment with hydrocortisone and fludrocortisone had lower long-term mortality rates and higher rate of shock reversal after 28 days compared to control patients 3.