Researchers find how hydrocortisone improve treatment of septic shock

CALIFORNIA: Sepsis is a global health problem, impacting 55 million patients and killing 11 million people each year. Sepsis treatment may include early detection, source management, antibiotics, fluids, vasopressors, and adjuvant therapy. For more than 50 years, corticosteroids have been studied as an additional therapy for septic shock.

Despite this substantial amount of evidence, questions about the effects of corticosteroids on mortality remain. An international team of researchers from UC San Francisco, Raymond Poincare AP-HP Hospital, Versailles SQY University, Paris-Saclay University and Inserm, and the George Institute for Global Health in Sydney studied the role of hydrocortisone in the management of adult patients with septic shock in a study published in the New England Journal of Medicine

Evidence: They discovered that, while hydrocortisone had a minor effect on overall survival, it was related with a reduction in the requirement for vasopressor medicines and an improvement in survival when given in combination with other corticosteroids.

The study, led by first authors Romain Pirracchio, MD, MPH, PhD, UCSF Professor of Anaesthesia, Djillali Annane, MD, PhD, and senior author Anthony Delaney, MBBS, MSc, PhD, was designed to assess the role of corticosteroids in the management of patients with septic shock, as well as the contradictory effects on mortality observed in previous research and treatment.

The research team performed a meta-analysis of the effect of hydrocortisone on patients with septic shock by pooling individual data from studies conducted between 1998 and 2019 including adult patients with sepsis or septic shock who received intravenous hydrocortisone at a maximum daily dose of 400 mg for at least 72 hours, or a placebo.

Individual patient data were available for 17 studies, and 7 of these provided 90-day mortality data. The primary endpoint was 90-day all-cause mortality. Secondary outcomes included mortality in ICU and discharge from hospital, at 28 and 180 days, and number of days without the need for vasopressor drugs to maintain cardiovascular function, without a ventilator, and the number of days without vital organ failure.

The researchers found that hydrocortisone was not associated with a significant reduction in mortality for patients with septic shock compared to placebo. Hydrocortisone was, however, associated with a significant increase, on average of 1.24 days, in the number of days without the need for vasopressor drugs.

The study also suggests that the association of fludrocortisone, a corticosteroid with a strong action on the regulation of water and sodium, with hydrocortisone might reduce mortality. "For the first time, the hydrocortisone" effects of hydrocortisone for the treatment of patients with septic shock could be studied by analyzing individual data from the main randomized trials published to date," said Pirracchio. "This study shows that if the effect of hydrocortisone on the mortality of septic shock is modest, this treatment makes it possible to spare the exposure of patients to vasopressor drugs and to prevent their complications. The combination of fludrocortisone with hydrocortisone seems to provide a greater benefit in terms of survival."