Corticosteroid Treatment and Intensive Insulin Therapy for Septic Shock in Adults
A Randomized Controlled Trial
- The COIITSS Study Investigators*
- *Authors/COIITSS Study Investigators writing committee: Djillali Annane, MD, General ICU, Hôpital Raymond Poincaré, Assistance Publique–Hôpitaux de Paris, Garches; Alain Cariou, MD, General ICU, Hôpital Cochin, AP-HP, Paris; Virginie Maxime, MD, General ICU, Hôpital Raymond Poincaré, AP-HP, Garches; Elie Azoulay, MD, General ICU, Hôpital Saint Louis, AP-HP, Paris; Gilles D’honneur, MD, Department of Anesthesiology, Hôpital Jean Verdier, AP-HP, Bondy; Jean François Timsit, MD, General ICU, Hôpital A. Michallon, Grenoble; Yves Cohen, MD, General ICU, Hôpital Avicenne, AP-HP, Bobigny; Michel Wolf, MD, General ICU, Hôpital Bichat, AP-HP, Paris; Muriel Fartoukh, MD, ICU, Hôpital Tenon, AP-HP, Paris; Christophe Adrie, MD, General ICU, Hôpital Delafontaine, Saint Denis; Charles Santré, MD, General ICU, Centre Hospitalier d’Annecy, Annecy; Pierre Edouard Bollaert, MD, General ICU, Hôpital Central, Nancy; Armelle Mathonet, MD, General ICU, Hôpital Cochin, AP-HP, Paris; Roland Amathieu, MD, Department of Anesthesiology, Hôpital Jean Verdier, AP-HP, Bondy; Alexis Tabah, MD, General ICU, Hôpital A. Michallon, Grenoble; Christophe Clec’h, MD, General ICU, Hôpital Avicenne, AP-HP, Bobigny; Julien Mayaud, MD, General ICU, Hôpital Saint Louis, AP-HP, Paris; and Julie Lejeune, PharmD, and Sylvie Chevret, MD, Département de Biostatistique et Informatique, Médicale Hôpital Saint Louis, AP-HP, Paris, France.
Abstract
Context Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear.
Objectives 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.
Design, Setting, and Patients A multicenter, 2 × 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.
Interventions 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-μg tablets once a day, each for 7 days.
Main Outcome Measure 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.
Trial Registration clinicaltrials.gov Identifier: NCT00320099
