Hydrocortisone therapy for patients with septic shock.
BACKGROUND
Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.


METHODS
In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test.


RESULTS
Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.


CONCLUSIONS
Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.)
Sprung
Charles L
CL
Hadassah Hebrew University Medical Center, Jerusalem, Israel 91120. sprung@cc.huji.ac.il
Annane
Djillali
D
Keh
Didier
D
Moreno
Rui
R
Singer
Mervyn
M
Freivogel
Klaus
K
Weiss
Yoram G
YG
Benbenishty
Julie
J
Kalenka
Armin
A
Forst
Helmuth
H
Laterre
Pierre-Francois
PF
Reinhart
Konrad
K
Cuthbertson
Brian H
BH
Payen
Didier
D
Briegel
Josef
J
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005045:Etomidate / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D017211:Treatment Failure
D018686:Anesthetics, Intravenous; D000893:Anti-Inflammatory Agents; D006728:Hormones; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D005045:Etomidate