1. Among patients with severe community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), hydrocortisone reduced the risk of death compared to placebo.
2. The frequency of adverse events was similar between the hydrocortisone and placebo groups.
Evidence Rating Level: 1 (Excellent)
Study Rundown: CAP is a prevalent lower respiratory infection affecting millions of individuals worldwide on an annual basis. The death rates of hospitalized and ICU patients with CAP remain significant despite advancements in care. Notably, the pathophysiology of pneumonia-related morbidities and mortality involves severe inflammation. Therefore, glucocorticoids have been investigated as a potential treatment for these patient populations. Despite some clinical benefits, mortality benefits have not been established. The current study was a placebo-controlled phase three trial to assess the effect of intravenous hydrocortisone, in addition to standard of care, among adult patients admitted to the ICU due to severe CAP. By 28 days, hydrocortisone resulted in a significantly lower risk of death than placebo, alongside lower intubation and vasopressor administration rates. The frequencies of hospital-acquired infections and gastrointestinal bleeding (major glucocorticoid-associated adverse events) were similar between the two groups. Hydrocortisone recipients received higher daily doses of insulin, however. The study was limited by the low observed mortality in the control group, exclusion of septic shock patients, and a low number of immunocompromised patients. Nevertheless, these results demonstrated a clear 28-day mortality benefit of hydrocortisone for ICU patients with severe CAP.
In-Depth [randomized controlled trial]: The current study was a randomized controlled trial assessing the impact of hydrocortisone on the clinical status of adult patients admitted to the ICU for severe CAP. The severity of pneumonia was defined as the presence of at least one of mechanical ventilation, high-flow oxygen administration, nonrebreathing mask usage, or a score ≥130 on the Pulmonary Severity Index. Exclusion criteria included a do-not-intubate order, influenza-related pneumonia, and septic shock. The primary outcome was all-cause mortality by day 28. Overall, 800 patients were randomized to receive intravenous hydrocortisone 200mg daily as guided by clinical improvement or a placebo. By 28 days, the mortality rate was 6.2% in the hydrocortisone group and 11.9% in the placebo group (absolute difference -5.6 percentage points; 95% Confidence Interval [CI], -9.6 to -1.7; p=006). The rate of endotracheal intubation among those not receiving mechanical ventilation at baseline was lower in the hydrocortisone group compared to placebo (hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86). Similarly, the rate of vasopressor initiation was lower in the hydrocortisone group (HR, 0.59; 95% CI, 0.40 to 0.86). The rates of serious adverse events, ICU-acquired infections, and gastrointestinal bleeding were comparable between the two groups. However, in the first week of therapy, hydrocortisone recipients received a higher median daily insulin dose than those receiving placebo. In summary, these results demonstrated a mortality benefit of early treatment with hydrocortisone among adults admitted to the ICU with severe CAP.
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