The aim of the Corticosteroids and Intensive Insulin Therapy for Septic Shock (COIITSS) open-label study was to evaluate the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone, since corticosteroid therapy has the potential to induce hyperglycaemia. As a secondary objective, the benefit of fludrocortisone in this setting was also investigated as there is scant data for this intervention.

The study investigators enrolled 509 adults with septic shock who presented with multiple organ dysfunction (Sequential Organ Failure Assessment score of 8 or more) and who were treated with hydrocortisone, from January 2006 to January 2009, in 11 intensive care units in France.

Patients were randomised to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone (n=126), continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone (n=129), conventional insulin therapy with hydrocortisone alone (n=138), or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone (n=116). 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. The primary outcome measure was in-hospital mortality or 90 –day mortality, and the follow up period was 180 days.

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 = 0.50).

Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycaemia (<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 = 0.003).

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 = 0.50).

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

An accompanying editorial discusses the implications of this study.