Clinical question: Do the anti-inflammatory and immunomodulatory effects of glucocorticoids decrease mortality among patients with severe community-acquired pneumonia (CAP)?
Background: CAP remains a major public health issue. Seven randomized controlled trials have shown that glucocorticoids have positive effects in patients with CAP of varying severity. However, except for one trial, none of them have shown a between-group difference regarding mortality. The Community-Acquired Pneumonia: Evaluation of Glucocorticoids (CAPE COD) trial evaluated whether early treatment with hydrocortisone reduced mortality at 28 days among patients admitted to intensive care for severe CAP.
Study design: Double-blind, randomized, controlled, superiority trial
Setting: 31 French centers by the members of the Clinical Research in Intensive Care and Sepsis-Trial Group for Evaluation and Research in Sepsis Network
Synopsis: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients showed that by day 28, death had occurred in 25 of 400 patients (6.2%; 95% CI, 3.9 to 8.6) in the hydrocortisone group, and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group. In the treatment group, patients received 200 mg daily hydrocortisone for either four or seven days as determined by clinical improvement, followed by tapering for a total of eight or 14 days.
Patients were classified as severe CAP if they met at least one of four criteria: the initiation of mechanical ventilation (invasive or non-invasive) with a positive end-expiratory pressure of at least 5 cm of water; the initiation of the administration of oxygen through a high flow nasal cannula with a ratio of the partial pressure of arterial oxygen to the inspired fraction of oxygen (PaO2:FIO2) of less than 300, with a FIO2 of 50% or more; for patients wearing non-breathing mask, an estimated PAO2:FiO2 ratio of less than 300, according to prespecified charts; or a score of more than 130 on the Pulmonary Severity Index. Patients with septic shock were excluded because the pathophysiological processes and role of glucocorticoids may differ.
Bottom line: Among patients with severe CAP being treated in the intensive care unit, those who received hydrocortisone had a lower risk of death by day 28 than those who received a placebo.
Citation: Dequin PF, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-41.
Dr. Shah is co-medical director of hospital medicine at High Point Medical Center in High Point, N.C., a hospitalist at Atrium Health Wake Forest Baptist, and an assistant professor in hospital medicine at Wake Forest University School of Medicine, both in Winston-Salem, N.C.