Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial

Abstract

Introduction: Critically ill patients can develop hyperglycaemia even if they do not have diabetes. Intensive insulin therapy decreases morbidity and mortality rates in patients in a surgical intensive care unit (ICU) and decreases morbidity in patients in a medical ICU. The effect of this therapy on patients in a mixed medical/surgical ICU is unknown. Our goal was to assess whether the effect of intensive insulin therapy, compared with standard therapy, decreases morbidity and mortality in patients hospitalised in a mixed ICU.

Methods: This is a prospective, randomised, non-blinded, single-centre clinical trial in a medical/surgical ICU. Patients were randomly assigned to receive either intensive insulin therapy to maintain glucose levels between 80 and 110 mg/dl (4.4 to 6.1 mmol/l) or standard insulin therapy to maintain glucose levels between 180 and 200 mg/dl (10 and 11.1 mmol/l). The primary end point was mortality at 28 days.

Results: Over a period of 30 months, 504 patients were enrolled. The 28-day mortality rate was 32.4% (81 of 250) in the standard insulin therapy group and 36.6% (93 of 254) in the intensive insulin therapy group (Relative Risk [RR]: 1.1; 95% confidence interval [CI]: 0.85 to 1.42). The ICU mortality in the standard insulin therapy group was 31.2% (78 of 250) and 33.1% (84 of 254) in the intensive insulin therapy group (RR: 1.06; 95%CI: 0.82 to 1.36). There was no statistically significant reduction in the rate of ICU-acquired infections: 33.2% in the standard insulin therapy group compared with 27.17% in the intensive insulin therapy group (RR: 0.82; 95%CI: 0.63 to 1.07). The rate of hypoglycaemia (< or = 40 mg/dl) was 1.7% in the standard insulin therapy group and 8.5% in the intensive insulin therapy group (RR: 5.04; 95% CI: 1.20 to 21.12).

Conclusions: IIT used to maintain glucose levels within normal limits did not reduce morbidity or mortality of patients admitted to a mixed medical/surgical ICU. Furthermore, this therapy increased the risk of hypoglycaemia.

Trial registration: clinicaltrials.gov Identifiers: 4374-04-13031; 094-2 in 000966421.

Trial registration: ClinicalTrials.gov NCT00966421.

Figure 1

Flow of participants through the trial.

Figure 2

Nutrition administered to all 504 patients during the first 10 days of intensive care. Feeding at 0 represents the administration of nutrition between admission and 7 a.m., and 1 represents feeding on the first day after admission, from 7 a.m. onwards. Nutrition in the two groups was similar. (a) Total caloric intakes areexpressed as mean values (with the 95% confidence intervals indicated by the error bar). (b) Nutrition administered by the enteral route are expressed as mean values, (with the 95% confidence intervals indicated by the error bar). (c) Nutrition administered by the parenteral route are expressed as mean values (with the 95% confidence intervals indicated by the error bar).

Figure 3

Daily blood glucose levels during the first 10 days of intensive care. Medians and interquartile ranges (IQR) during the ICU stay (time) are shown for the two treatment arms.