Intensive care unit (ICU) patients commonly display hyperglycemia, even without previously known diabetes. It was demonstrated that hyperglycemia was associated with increased hospital mortality in various medical and surgical ICU situations. However, discrepant results from recent randomized, clinical trials of tight blood glucose control in ICUs have not allowed conclusions regarding whether there is a causal link between hyperglycemia and ICU mortality. In addition to the mean blood glucose level, glucose variability has recently been emphasized as an independent predictor of ICU and hospital mortality. This concept has been described in a wide variety of medical, surgical and trauma ICU patients. In all of these settings, glycemic variability was measured with various indices but was steadily associated with ICU and/or hospital mortality in non-diabetic ICU patients. Conversely, glycemic variability was either weakly or not associated with mortality in ICU patients with previously known diabetes. Notably, all of these data have been observational, and interventional trials remain lacking to assess the impact of glycemic variability reduction on ICU mortality and thus to demonstrate causality. However, glycemic variability was considered sufficiently important to be mentioned in recent international guidelines for the management of hyperglycemia in critically ill patients. In these publications, experts from the American College of Critical Care Medicine emphasized that glycemia should be maintained at less than 9.9 mmol/L in ICU patients while avoiding hypoglycemia and minimizing glycemic variability. To achieve these goals, computer-based insulin infusion protocols have demonstrated their superiority to paper-based protocols. Glucose concentrations, variation per unit of time between the last and current glucose measurements, insulin dosage, and carbohydrate intake were the main input variables used in these different computerized algorithms. However, such protocols are not widely available because commercial systems have licensing fees and academic protocols do not always go beyond the pilot phase.

To address this issue, the investigators adapted a previously validated, paper-based, dynamic protocol (DP) to an actual recommended glycemic target range. Our aim was to assess the efficacy, safety, feasibility and acceptance by nurses of this dynamic insulin protocol, compared to a paper-based, sliding scale static protocol (SP).

Inclusion Criteria:

• Male or female adult patient admitted to intensive care unit
• Intensive care unit stay > 48 hours
• Stress hyperglycemia above 9.9 mmil/L indicating the need of continuous intravenous insulin infusion

Exclusion Criteria:

• Previous diabetes
• Acute metabolic event (ketoacidosis or hyperosmolarity)
• Insulin/dextrose infusion for hyperkalemia treatment

This prospective trial involved adult patients who were admitted to the medical intensive care department of a French university hospital to compare the effects of two continuous intravenous insulin infusion (CIII) protocols on glycemic variability. According to the local protocol, patients with two consecutive capillary blood glucose measurements greater than 180 mg/dL (9.9 mmol/L), one hour apart, were considered to require CIII and were included in the trial. All of the patients or their family members received written information about the trial.