Medical ICU Paper-based Dynamic Insulin Protocol

Impact of a Paper-based Dynamic Insulin Infusion Protocol on Glycemic Variability, Time in Target and Hypoglycemic Risk: a Stepped Wedge Trial in Medical ICU Patients

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).

Study Overview

• Status: Completed
• Conditions: Stress Hyperglycemia
• Intervention / Treatment: Other: dynamic insulin protocol; Other: static insulin protocol

• Study Type: Observational
• Enrollment (Actual): 131

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
dynamic insulin protocol; patients received intravenous insulin infusion according to a dynamic insulin protocol	Other: dynamic insulin protocol; Adaptation of insulin infusion rate according to hourly capillary blood glucose and dynamic insulin protocol
static insulin protocol; patients received intravenous insulin infusion according to a static insulin protocol	Other: static insulin protocol; Adaptation of insulin infusion rate according to hourly capillary blood glucose and static insulin protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MAGE (mean amplitude of glycemic excursion) index	calculated during the 5 first days after beginning of insulin infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
MAG: mean absolute glucose change	calculated during the 5 first days after beginning of insulin infusion
LI: lability index	calculated during the 5 first days after beginning of insulin infusion
SD: standard deviation of glycemia	calculated during the 5 first days after beginning of insulin infusion
CV: coefficient of variation of glycemia	calculated during the 5 first days after beginning of insulin infusion
LBGI: low blood glucose index	calculated during the 5 first days after beginning of insulin infusion
HBGI: high blood glucose index	calculated during the 5 first days after beginning of insulin infusion
GRADE: glycemic risk assessment diabetes equation	calculated during the 5 first days after beginning of insulin infusion
M-Value	calculated during the 5 first days after beginning of insulin infusion
mean blood glucose	calculated during the 5 first days after beginning of insulin infusion
time spent in the target range (140 to 180 mg/dL - 7.7 to 9.9 mmol/L)	calculated during the 5 first days after beginning of insulin infusion
low blood glucose episodes (less than 80 and 60 mg/dL - 4.4 and 3.3 mmol/L) (n/patient)	measured during the 5 first days after beginning of insulin infusion
severe hypoglycemia (less than 40 mg/dL - 2.2 mmol/L) (n/patient)	measured during the 5 first days after beginning of insulin infusion
time before the first glucose value in the target range (h)	calculated during the 5 first days after beginning of insulin infusion

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Investigators: Study Chair: damien du cheyron, PhD, University Hospital, Caen

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: July 27, 2016
• First Posted (Estimate): July 28, 2016

Study Record Updates

• Last Update Posted (Estimate): July 28, 2016
• Last Update Submitted That Met QC Criteria: July 27, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: VARIREA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided