Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.
BACKGROUND
Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear.


OBJECTIVE
To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone.


METHODS
A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France.


METHODS
Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days.


METHODS
In-hospital mortality.


RESULTS
Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50).


CONCLUSIONS
Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality.


BACKGROUND
clinicaltrials.gov Identifier: NCT00320099.
Annane
Djillali
D
Cariou
Alain
A
Maxime
Virginie
V
Azoulay
Elie
E
D'honneur
Gilles
G
Timsit
Jean François
JF
Cohen
Yves
Y
Wolf
Michel
M
Fartoukh
Muriel
M
Adrie
Christophe
C
Santré
Charles
C
Bollaert
Pierre Edouard
PE
Mathonet
Armelle
A
Amathieu
Roland
R
Tabah
Alexis
A
Clec'h
Christophe
C
Mayaux
Julien
J
Lejeune
Julie
J
Chevret
Sylvie
S
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005438:Fludrocortisone; D006854:Hydrocortisone