International study clarifies role of hydrocortisone in the management of patients with septic shock

Hydrocortisone is not associated with a significant decrease in mortality from any cause 90 days after treatment in adults with septic shock, but still has other benefits, according to results published in NEJM Evidence today.

The meta-analysis, involving almost 8,000 participants was a collaboration between the Raymond Poincaré AP-HP Hospital, Versailles SQY University, Paris-Saclay University and Inserm, in conjunction with The George Institute for Global Health in Sydney, Australia and the University of California, San Francisco, USA.

Professor Djillali Annane, Director of the Department of Intensive Care at Raymond Poincaré AP-HP Hospital, said it was the first time the effects of hydrocortisone for the treatment of patients with septic shock had been studied by analysing individual data from the main randomised trials published to date.^1,2

“The results suggest that even if the effect of hydrocortisone on mortality is modest, it may reduce patients’ exposure to other drugs and prevent their complications,” he said.

Sepsis³ affects 55 million people worldwide and causes 11 million deaths per year. Treatments include early recognition, controlling the source of the infection, antibiotics, fluids, vasopressors (drugs that cause the constriction of blood vessels, thereby elevating low blood pressure), and other add-on therapies.

Hydrocortisone has been studied as a supplement to other therapies for septic shock for more

than 50 years. While multiple studies have assessed whether the addition of corticosteroids might reduce mortality or be associated with other benefits such as reducing the duration of the condition, the number of days requiring mechanical ventilation and length of stay in ICU, some uncertainty remains.

In this meta-analysis, the research team pooled individual data from studies conducted between 1998 and 2019 including 7882 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 main measurement used to determine the effect of hydrocortisone was 90-day mortality from any cause.

Researchers also looked at mortality while in ICU and after discharge from hospital. They also considered the number of days without the need for vasopressor drugs to maintain cardiovascular function, without the need for mechanical ventilation, and the number of days without vital organ failure.

“We saw that hydrocortisone was not associated with a significant reduction in mortality for patients with septic shock compared to placebo,” said Prof Pirracchio, from the University of California, San Francisco.

“But hydrocortisone was associated with a significant increase, an average of 1.24, in the number of days without the need for vasopressor drugs,” he added.

The study also suggests that adding fludrocortisone - a corticosteroid with a strong action on the regulation of water and sodium - along with hydrocortisone might reduce mortality.

Associate Professor Anthony Delaney, Senior Staff Specialist in Intensive Care Medicine, at Royal North Shore Hospital, Sydney, and Professorial Fellow, The George Institute for Global Health, said that hydrocortisone was an important supplementary treatment for patients with septic shock.

“Less time on vasopressors, less time spent on a ventilator and fewer days in the ICU will be important for both patients and the health care system,” he said.

“But whether fludrocortisone in conjunction with hydrocortisone is better than hydrocortisone alone, needs to be further tested in a larger randomised controlled trial,” he added.

References

1. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med 2018; 378:809-818. DOI: 10.1056/NEJMoa1705716.
2. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 2018; 378:797-808. DOI: 10.1056/NEJMoa1705835
3. Acute state of dysregulation of the body's response to an infection (bacterial, viral, fungal or parasitic) resulting in the loss of organ function and a vital risk for the patient.

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