Hydrocortisone in Patients With Septic Shock
Sprung CL, Annane D, Keh D, et al
N Engl J Med. 2008;358:111-124
Although hydrocortisone is widely used in patients with septic shock, survival benefits have been reported only in patients who did not respond to the initial administration of corticotropin. So, is hydrocortisone really beneficial at all in patients with septic shock? To answer this question the authors conducted a large multicenter randomized trial comparing 251 patients treated with hydrocortisone (50 mg intravenously every 6 hours for 5 days) with patients treated with a placebo. The study endpoint was death in those patients who were unresponsive to an initial corticotropin stimulus. Mortality rate at the conclusion of the study was similar in the 2 groups of patients who did not have a response to corticotropin: 39% in treated patients vs 36% in controls. Mortality was also the same in the 2 groups who did have an initial response (nearly 29% in both groups). Complications such as superinfection, hyperglycemia, and hypernatremia were more frequent in the treated group.
High-dose corticosteroid therapy for septic shock proved to be ineffective in previous large, randomized trials. This study of low or "physiologic-dose" corticosteroids found similar negative results regardless of the initial adrenal response to corticotropin. One drawback of the trial is that the actual number of patients accrued was smaller than the estimated number (800) that would have been required to rule out a negative result because of inadequate study power. This limitation is understandable as it is difficult to recruit patients for this type of study. In view of the findings, however, it seems unlikely that a larger trial would have given a different result.
Abstract
Sprung CL, Annane D, Keh D, et al
N Engl J Med. 2008;358:111-124
Although hydrocortisone is widely used in patients with septic shock, survival benefits have been reported only in patients who did not respond to the initial administration of corticotropin. So, is hydrocortisone really beneficial at all in patients with septic shock? To answer this question the authors conducted a large multicenter randomized trial comparing 251 patients treated with hydrocortisone (50 mg intravenously every 6 hours for 5 days) with patients treated with a placebo. The study endpoint was death in those patients who were unresponsive to an initial corticotropin stimulus. Mortality rate at the conclusion of the study was similar in the 2 groups of patients who did not have a response to corticotropin: 39% in treated patients vs 36% in controls. Mortality was also the same in the 2 groups who did have an initial response (nearly 29% in both groups). Complications such as superinfection, hyperglycemia, and hypernatremia were more frequent in the treated group.
High-dose corticosteroid therapy for septic shock proved to be ineffective in previous large, randomized trials. This study of low or "physiologic-dose" corticosteroids found similar negative results regardless of the initial adrenal response to corticotropin. One drawback of the trial is that the actual number of patients accrued was smaller than the estimated number (800) that would have been required to rule out a negative result because of inadequate study power. This limitation is understandable as it is difficult to recruit patients for this type of study. In view of the findings, however, it seems unlikely that a larger trial would have given a different result.
Abstract