Providing intravenous stress-dose hydrocortisone for 1 week reduced the rate of hospital-acquired pneumonia among intubated patients with multiple trauma, according to a report in the March 23/30 issue of JAMA.
The treatment also decreased the number of days on mechanical ventilation, the incidence of acute respiratory distress syndrome, and the length of stay in the ICU, said Dr. Antoine Roquilly of the departments of anesthesiology and intensive care medicine, University Hospital of Nantes (France), and his associates.
The researchers evaluated stress-dose hydrocortisone therapy in a double-blind clinical trial because it was thought that the treatment might "attenuate the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection." They postulated that this would be particularly helpful in reducing the prevalence of hospital-acquired pneumonia, the major cause of infection among trauma patients.
A total of 150 intubated patients with multiple trauma who were aged older than 15 years and were expected to require mechanical ventilation for more than 48 hours were enrolled at seven ICUs in France over a 3-year period. Half were randomly assigned to receive stress-dose (200 mg/day) IV hydrocortisone and half to receive placebo infusions for 7 days.
The study’s primary end point was the rate of hospital-acquired pneumonia within 28 days. The subjects were evaluated twice daily for the development of pneumonia during the first month in the ICU.
Of the 73 patients treated with hydrocortisone who completed the trial, 26 (36%) developed pneumonia, a significantly lower rate than the 39 (51%) of 76 patients in the placebo group who developed pneumonia. The findings were similar in an intention-to-treat analysis, Dr. Roquilly and his colleagues said (JAMA 2011;305:1201-9).
When the analysis was restricted to the 103 patients who showed corticosteroid insufficiency at baseline, the results were similar: a 36% rate of pneumonia with hydrocortisone therapy and a 54% rate with placebo.
"Subgroup analysis suggests that hydrocortisone was particularly effective for patients with traumatic brain injury," the investigators noted.
Among those with traumatic brain injury who presented with corticosteroid insufficiency, 41% in the hydrocortisone group developed pneumonia, compared with 71% in the placebo group.
The short duration of exposure to IV hydrocortisone did not adversely affect the 47 patients who did not have corticosteroid insufficiency at baseline, they pointed out.
Patients who received hydrocortisone were weaned from mechanical ventilation earlier (12 vs. 16 days) and had a shorter length of ICU stay (18 vs. 24 days) than did those who received placebo. Three patients (4%) in the hydrocortisone group developed acute respiratory distress syndrome, compared with 11 (14%) in the placebo group.
The two groups did not differ with respect to mortality, the rate of other infections, the number of organ failures, or the duration of vasopressor support.
Both these beneficial effects and the safety of hydrocortisone therapy must be confirmed in future studies of ICU patients, particularly in those with traumatic brain injury, Dr. Roquilly and his associates said.
This study was sponsored by the University of Nantes. The French Ministry of Health provided additional support. No financial conflicts of interest were reported.
"In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune inflammatory response after injury would better guide this therapeutic approach," they noted.
Dr. Bulger and Dr. Cuschieri are in the department of surgery at the University of Washington, Seattle. They reported no financial conflicts of interest.