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Liberal Glucose Control in ICU Patients With Diabetes: A Before-and-After Study*

Luethi, Nora MD1; Cioccari, Luca MD1; Biesenbach, Peter MD1; Lucchetta, Luca MD1; Kagaya, Hidetoshi MD1; Morgan, Rhys MD1; Di Muzio, Francesca MD1,2; Presello, Barbara MD1,3; Gaafar, Duaa MD1; Hay, Alison MD1; Crisman, Marco MD1,3; Toohey, Roisin BSc1; Russell, Hollie BSc1; Glassford, Neil J. MRCP1,4; Eastwood, Glenn M. PhD1,4; Ekinci, Elif I. MBBS, PhD5,6; Deane, Adam M. MD, PhD7; Bellomo, Rinaldo MD1,4; Mårtensson, Johan MD, PhD1,8

doi: 10.1097/CCM.0000000000003087
Clinical Investigations

Objectives: To assess the feasibility, biochemical efficacy, and safety of liberal versus conventional glucose control in ICU patients with diabetes.

Design: Prospective, open-label, sequential period study.

Setting: A 22-bed mixed ICU of a tertiary hospital in Australia.

Patients: We compared 350 consecutive patients with diabetes admitted over 15 months who received liberal glucose control with a preintervention control population of 350 consecutive patients with diabetes who received conventional glucose control.

Interventions: Liberal control patients received insulin therapy if glucose was greater than 14 mmol/L (target: 10–14 mmol/L [180–252 mg/dL]). Conventional control patients received insulin therapy if glucose was greater than 10 mmol/L (target: 6–10 mmol/L [108–180 mg/dL]).

Measurements and Main Results: We assessed separation in blood glucose, insulin requirements, occurrence of hypoglycemia (blood glucose ≤ 3.9 mmol/L [70 mg/dL]), creatinine and white cell count levels, and clinical outcomes. The median (interquartile range) time-weighted average blood glucose concentration was significantly higher in the liberal control group (11.0 mmol/L [8.7–12.0 mmol/L]; 198 mg/dL [157–216 mg/dL]) than in the conventional control group (9.6 mmol/L [8.5–11.0 mmol/L]; 173 mg/dL [153–198 mg/dL]; p < 0.001). Overall, 132 liberal control patients (37.7%) and 188 conventional control patients (53.7%) received insulin in ICU (p < 0.001). Hypoglycemia occurred in 6.6% and 8.6%, respectively (p = 0.32). Among 314 patients with glycated hemoglobin A1c greater than or equal to 7%, hypoglycemia occurred in 4.1% and 9.6%, respectively (p = 0.053). Trajectories of creatinine and white cell count were similar in the groups. In multivariable analyses, we found no independent association between glucose control and mortality, duration of mechanical ventilation, or ICU-free days to day 30.

Conclusions: In ICU patients with diabetes, during a period of liberal glucose control, insulin administration, and among patients with hemoglobin A1c greater than or equal to 7%, the prevalence of hypoglycemia was reduced, without negatively affecting serum creatinine, the white cell count response, or other clinical outcomes. (Trial Registration: Australian New Zealand Clinical Trials Registry; ACTRN12615000216516).

1Department of Intensive Care, Austin Hospital, Heidelberg, VIC, Australia.

2Department of Anesthesia and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli, Roma, Italy.

3Department of Perioperative, Intensive Care and Emergency Medicine, Università degli Studi di Trieste, Ospedale di Cattinara, Strada di Fiume, Trieste, Italy.

4Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Prahran, VIC, Australia.

5Department of Endocrinology and Diabetology, Austin Hospital, Heidelberg, VIC, Australia.

6Department of Medicine Austin Health, The University of Melbourne, Melbourne, VIC, Australia.

7Department of Intensive Care, Royal Melbourne Hospital, Parkville, VIC, Australia.

8Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.

*See also p. 1019.

This work was performed at Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, VIC, Australia.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Supported, in part, by grants from the Austin Hospital Intensive Care Trust Fund. The Avant Doctors-In-Training Research Scholarship supported Dr. Glassford.

Drs. Hay and Martensson’s institution received funding from the Austin Hospital Intensive Care Trust Fund. Dr. Glassford received other support from AVANT Mutual, Doctors in Training, Scholarship 2014–2015 (paid research salary). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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