Administering hydrocortisone early improves survival in community-acquired pneumonia patients

Scientists from the Regional University Hospital Center in Tours, France, and the National Institute of Health and Medical Research (INSERM) set out to determine if the anti-inflammatory and immunomodulatory effects of glucocorticoids could reduce mortality in patients with severe community-acquired pneumonia (CAP). After a phase 3, multicentre, double-blind, randomized and controlled trial, they demonstrated hydrocortisone administered early does indeed improve survival. These results were very encouraging considering “the high prevalence of pneumonia in the general population and the good control of hydrocortisone,” noted INSERM in a press release. Read: Triggers of pneumonia in rheumatoid arthritis CAP remains a major public health problem. There were 489 million cases of lower respiratory tract infections worldwide in 2019. In the same year, CAP was the ninth leading cause of death in the United States and the leading cause of death from infection (about 50,000 deaths). In more economically developed countries, the monthly death rate among patients hospitalized with CAP is 10-12%; this rate can reach 30% in patients using from mechanical ventilation. CAP “can lead to intense lung and systemic inflammation, which results in impaired gas exchange, sepsis and organ failure, as well as an increased risk of death. Glucocorticoids have potent anti-inflammatory and immunomodulatory activities that mitigate the consequences of pneumonia,” the researchers note in the study published in the New England Journal of Medicine. Read: Several southern Ontario public health units warn whooping cough on the rise They point out that the medical literature shows that synthetic corticosteroids facilitate the development of less severe CAP (not hospitalized in intensive care). For severe forms, an improvement in survival has already been mentioned, but without definitive proof. Funded by the French Ministry of Health, the CAPE COD trial (Community-Acquired Pneumonie: Evaluation of COrticosteroiDs) was therefore intended to determine whether hydrocortisone could provide a benefit in the management of severe forms by reducing mortality at 28 days in patients admitted to an intensive care unit. It was conducted in 31 French hospitals with a total of 800 participants—including all adult patients admitted to the intensive care unit for severe CAP, unless they were not intubable, had septic shock or if the pneumonia was caused by influenza. All received care in accordance with the recommendations (care, antibiotic therapy, respiratory care, etc.). They were separated into two randomized groups: the first received continuous IV hydrocortisone (200 mg/day for four days), the second a placebo. Depending on the clinical improvement, the medical team then decided to continue the corticosteroids for four or 10 additional days, the dose being gradually reduced and then interrupted when leaving intensive care. Increase in survival rates After four weeks, mortality was 6.2% in patients treated with hydrocortisone, and 11.9% in those who received placebo, a statistically significant difference (p=0.006). Mortality at 90 days remained lower in the group treated with hydrocortisone. The proportion of patients who had been intubated was also lower in the hydrocortisone group (18% versus 29.5%) as well as among those who received vasoconstrictor drugs (15.3% versus 25%). In terms of tolerance, 70 adverse events were recorded on day 28 in the hydrocortisone group and 99 in the placebo group. The frequency of nosocomial infections and gastrointestinal bleeding was similar in the two groups. Patients treated with hydrocortisone also received higher doses of insulin during the first seven days of treatment. “Thus, this study clearly shows an increase in survival in patients with severe community-acquired pneumonia admitted to intensive care," noted the INSERM release. "This is a major result, because this suspected effect had never been proven to date . . .. Hydrocortisone is an old drug, with a perfectly known safety profile, little expense and is readily available." The mechanisms explaining this effectiveness still remain poorly understood. The researchers point to “an effect of reduction of the pulmonary inflammation, a modulation of the response of the immune system, and undoubtedly other mechanisms.” More analysis will be carried out in France in order to better understand these mechanisms. This article has been translated from its original French and first appeared on our sister site Profession Santé.

Administering hydrocortisone early improves survival in community-acquired pneumonia patients

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