"Hydrocortisone in Severe Community-Acquired Pneumonia".

The New England Journal of Medicine. 2023.

Clinical Question

Does the administration of hydrocortisone reduce 28-day mortality in patients with severe community-acquired pneumonia being treated in the ICU?

Bottom Line

In patients with severe community-acquired pneumonia being treated in the ICU, the administration of hydrocortisone resulted in lower 28-day mortality compared with placebo.

Major Points

Guidelines

The results of this study could influence future guidelines on the therapy for severe community-acquired pneumonia in the ICU.

Design

Double-blind, randomized, controlled superiority trial.

Population

795 adults admitted to the ICU for severe community-acquired pneumonia.

Inclusion Criteria
- Adults ≥18 years
- Severe community-acquired pneumonia requiring ICU admission
- Presence of specific severity criteria for pneumonia

Exclusion Criteria
- Do-not-intubate order
- Pneumonia caused by influenza
- Septic shock at baseline
- Other specified criteria

Baseline Characteristics
- Gender distributions, pathogen profiles, and other baseline health characteristics were detailed.

Interventions

Patients randomized to hydrocortisone group received:
- 200mg intravenous hydrocortisone daily for 4 or 7 days based on clinical improvement, followed by tapering over a total of 8 or 14 days
- Standard therapy for severe community-acquired pneumonia (antibiotics and supportive care)

Patients in placebo group received:
- Intravenous saline with an identical regimen to the hydrocortisone group

Outcomes

Primary Outcome:
- 28-day mortality rate (6.2% in the hydrocortisone group versus 11.9% in the placebo group, P=0.006)

Secondary Outcomes:
- 90-day mortality rate
- Length of ICU stay
- Ventilator-free days and vasopressor-free days
- Incidence of endotracheal intubation in patients not ventilated at baseline
- Initiation of vasopressor therapy by day 28
- Changes in the Pao2:Fio2 ratio and SOFA score by day 7
- Quality of life assessed by SF-36 scores

Criticisms

- Lower than expected mortality in the control group suggests lower severity of illness than anticipated.
- No standardized microbiologic evaluation, with many patients with no documented pathogen.
- Exclusion of patients with septic shock.
- Did not evaluate the reversibility of glucocorticoid-induced hyperglycemia.

Funding

Funded by the French Ministry of Health.

Further Reading

Complete trial data and supplementary material are available at NEJM.org.