N Engl J Med 2023 Mar 21
Hydrocortisone in Severe Community-Acquired Pneumonia.
Abstract
Background
Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear.
Methods
In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days.
Results
A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [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 (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment.
Conclusions
Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).
Related Questions
When would you consider glucocorticoids as adjunctive therapy for for community-acquired pneumonia outside of the ICU setting?
Thank you for bringing this new study to my attention; I hadn't seen it yet. After reviewing the article, my practice regarding steroids remains unchanged. While the trial was well-executed, and it is laudable to see such research coming out of a limited-resource setting, that environment differs si...
When do you consider a trial of steroids for acute hypoxemic respiratory failure when there are no other clear indications for its use (i.e., COVID, COPD, organizing pneumonia, etc.)?
We will consider a trial of systemic corticosteroids in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) within 14 days of onset—even when no other clear indications are present (such as COVID-19, COPD, or organizing pneumonia). This is supported by the 2024 American Thora...
Have you incorporated the use of steroids for patients with severe community-acquired pneumonia?
Yes, the evidence is pointing toward starting steroids (hydrocortisone at 200mg total daily dose) early (in the first 24 hours) in patients with severe CAP who do NOT have influenza. In septic shock caused by CAP, steroid recs follow the septic shock guidelines. Dequin et al., PMID 36942789 showed t...
Do you start steroid therapy in a patient with pure ARDS without septic shock, or would you only consider steroids only in those with severe community acquired pneumonia?
I do not routinely start corticosteroids for pure ARDS, septic shock, or severe community-acquired pneumonia. In my mind, the DEXA-ARDS study was underpowered to answer the question. The recently published ESCAPE and CAPE-COD trials yielded conflicting results in CAP. In my mind, before adopting cor...