Hydrocortisone Reduced Mortality in Patients With Severe Pneumonia

For patients admitted to the intensive care unit with severe community-acquired pneumonia, treatment with hydrocortisone led to a lower risk of death at 28 days versus placebo, a phase III randomized trial in France showed.

Among nearly 800 patients who received standard therapy, death had occurred by day 28 in 6.2% of those in the hydrocortisone group compared with 11.9% of those in the placebo group (P=0.006), reported Pierre‑François Dequin, MD, PhD, of Hôpital Bretonneau in Paris, and colleagues in the New England Journal of Medicine.

Results were consistent across subgroups. For example, among the patients who did not receive mechanical ventilation at baseline, endotracheal intubation was performed in 18% of those in the hydrocortisone group versus 29.5% of those in the placebo group (HR 0.59, 95% CI 0.40-0.86).

For the patients who were not receiving vasopressors at baseline, this therapy was initiated in 15.3% of the hydrocortisone group compared with 25% of the placebo group (HR 0.59, 95% CI 0.43-0.82).

Those treated with hydrocortisone also had better survival outcomes at day 90, with a mortality rate of 9.3% in the hydrocortisone group versus 14.7% in the placebo group.

“Our data do not indicate any particular safety issues, including no between-group difference in the occurrence of hospital-acquired infections,” Dequin and team wrote, adding that hydrocortisone also did not result in any increased gastrointestinal bleeding.

However, they noted, patients in the hydrocortisone group did receive higher doses of insulin during the first 7 days of treatment, “which is consistent with the pharmacodynamic effects of glucocorticoids.”

The results of another recent trial in critically ill patients with severe community-acquired pneumonia showed that methylprednisolone did not significantly reduce mortality by day 60 versus placebo (adjusted OR 0.90, 95% CI 0.57-1.40).

“The pharmacodynamic properties of glucocorticoids may differ, including the balance between mineralocorticoid and glucocorticoid effects,” Dequin and colleagues suggested.

In the U.S., more than 1.5 million adults are hospitalized for community-acquired pneumonia every year. Among high-income countries, the monthly death rate for patients who are hospitalized with community-acquired pneumonia is about 10% to 12%, and can reach as high as 30% for those who receive any type of mechanical ventilation.

This double-blind trial was conducted across 31 centers in France from October 2015 to March 2020. The researchers included 795 patients in the final analysis. Median age was 67, and about 70% were men. Comorbidities included chronic obstructive pulmonary disease, asthma, and diabetes.

All patients received “state-of-the-art” standard therapy, including antibiotics and supportive care. Patients in the treatment group received 200 mg of intravenous hydrocortisone for 8 or 14 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days.

Dequin and colleagues noted that the observed mortality rate in the control group was lower than anticipated, “which may indicate a lower severity of illness than expected.”