Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.
BACKGROUND
Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.


OBJECTIVE
To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.


METHODS
Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.


METHODS
Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.


METHODS
Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.


METHODS
Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).


RESULTS
One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.


CONCLUSIONS
In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events.
Service de Réanimation Médicale, Hôpital Raymond Poincaré, 104 Blvd Raymond Poincaré, 92380 Garches, France. djillali.annane@rpc.ap-hop-paris.fr
Djillali
D
Annane
Véronique
V
Sébille
Claire
C
Charpentier
Pierre-Edouard
PE
Bollaert
Bruno
B
François
Jean-Michel
JM
Korach
Gilles
G
Capellier
Yves
Y
Cohen
Elie
E
Azoulay
Gilles
G
Troché
Philippe
P
Chaumet-Riffaud
Philippe
P
Chaumet-Riffaut
Eric
E
Bellissant
D000309:Adrenal Insufficiency / Q000150:complications* / Q000175:diagnosis; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005438:Fludrocortisone / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D014662:Vasoconstrictor Agents; D005438:Fludrocortisone; D006854:Hydrocortisone