title: Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.
abstract: 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.
authors.forename: Djillali
authors.initials: D
authors.lastname: Annane
authors.forename: Alain
authors.initials: A
authors.lastname: Cariou
authors.forename: Virginie
authors.initials: V
authors.lastname: Maxime
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Gilles
authors.initials: G
authors.lastname: D'honneur
authors.forename: Jean François
authors.initials: JF
authors.lastname: Timsit
authors.forename: Yves
authors.initials: Y
authors.lastname: Cohen
authors.forename: Michel
authors.initials: M
authors.lastname: Wolf
authors.forename: Muriel
authors.initials: M
authors.lastname: Fartoukh
authors.forename: Christophe
authors.initials: C
authors.lastname: Adrie
authors.forename: Charles
authors.initials: C
authors.lastname: Santré
authors.forename: Pierre Edouard
authors.initials: PE
authors.lastname: Bollaert
authors.forename: Armelle
authors.initials: A
authors.lastname: Mathonet
authors.forename: Roland
authors.initials: R
authors.lastname: Amathieu
authors.forename: Alexis
authors.initials: A
authors.lastname: Tabah
authors.forename: Christophe
authors.initials: C
authors.lastname: Clec'h
authors.forename: Julien
authors.initials: J
authors.lastname: Mayaux
authors.forename: Julie
authors.initials: J
authors.lastname: Lejeune
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
mesh_terms: 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
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005438:Fludrocortisone; D006854:Hydrocortisone