Software-guided versus nurse-directed blood glucose control in critically ill patients: the LOGIC-2 multicenter randomized controlled clinical trial

Jasperina Dubois, Tom Van Herpe, Roosmarijn T van Hooijdonk, Ruben Wouters, Domien Coart, Pieter Wouters, Aimé Van Assche, Guy Veraghtert, Bart De Moor, Joost Wauters, Alexander Wilmer, Marcus J Schultz, Greet Van den Berghe, Dieter Mesotten, Jasperina Dubois, Tom Van Herpe, Roosmarijn T van Hooijdonk, Ruben Wouters, Domien Coart, Pieter Wouters, Aimé Van Assche, Guy Veraghtert, Bart De Moor, Joost Wauters, Alexander Wilmer, Marcus J Schultz, Greet Van den Berghe, Dieter Mesotten

Abstract

Background: Blood glucose control in the intensive care unit (ICU) has the potential to save lives. However, maintaining blood glucose concentrations within a chosen target range is difficult in clinical practice and holds risk of potentially harmful hypoglycemia. Clinically validated computer algorithms to guide insulin dosing by nurses have been advocated for better and safer blood glucose control.

Methods: We conducted an international, multicenter, randomized controlled trial involving 1550 adult, medical and surgical critically ill patients, requiring blood glucose control. Patients were randomly assigned to algorithm-guided blood glucose control (LOGIC-C, n = 777) or blood glucose control by trained nurses (Nurse-C, n = 773) during ICU stay, according to the local target range (80-110 mg/dL or 90-145 mg/dL). The primary outcome measure was the quality of blood glucose control, assessed by the glycemic penalty index (GPI), a measure that penalizes hypoglycemic and hyperglycemic deviations from the chosen target range. Incidence of severe hypoglycemia (<40 mg/dL) was the main safety outcome measure. New infections in ICU, duration of hospital stay, landmark 90-day mortality and quality of life were clinical safety outcome measures.

Results: The median GPI was lower in the LOGIC-C (10.8 IQR 6.2-16.1) than in the Nurse-C group (17.1 IQR 10.6-26.2) (P < 0.001). Mean blood glucose was 111 mg/dL (SD 15) in LOCIC-C versus 119 mg/dL (SD 21) in Nurse-C, whereas the median time-in-target range was 67.0% (IQR 52.1-80.1) in LOGIC-C versus 47.1% (IQR 28.1-65.0) in the Nurse-C group (both P < 0.001). The fraction of patients with severe hypoglycemia did not differ between LOGIC-C (0.9%) and Nurse-C (1.2%) (P = 0.6). The clinical safety outcomes did not differ between groups. The sampling interval was 2.3 h (SD 0.5) in the LOGIC-C group versus 3.0 h (SD 0.8) in the Nurse-C group (P < 0.001).

Conclusions: In a randomized controlled trial of a mixed critically ill patient population, the use of the LOGIC-Insulin blood glucose control algorithm, compared with blood glucose control by expert nurses, improved the quality of blood glucose control without increasing hypoglycemia.

Trial registration: ClinicalTrials.gov, NCT02056353 . Registered on 4 February 2014.

Keywords: Blood glucose control; Computer algorithm; Glycemic penalty index; Infection; Quality of blood glucose control; Sepsis; Time-in-target.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol and informed consent documents were approved by the Belgian Federal Agency for Medicines and Health Products (80 M0563) (Additional file 2) and the institutional review boards of each participating center. The trial was registered on ClinicalTrials.gov (NCT02056353) on 4 February 2014.

Consent for publication

Not applicable.

Competing interests

Tom Van Herpe, Bart De Moor and Greet Van den Berghe are inventors on EP1487518. Bart De Moor and Greet Van den Berghe are inventors on US2005171503. Roosmarijn T.M. van Hooijdonk reports consulting work for Medtronic Inc., GlySure Ltd and research support from Medtronic Inc. and Optiscan Biomedical - all fees and financial support were paid to the institution. Marcus J. Schultz reports receiving consultant fees from Medtronic Inc., GlySure Ltd, Edwards Life Sciences and Roche Diagnostics, and financial support from Medtronic Inc. and OptiScan Biomedical - all fees and financial support were paid to the institution. All other authors declare that they have no competing interests.

Publisher’s Note

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Figures

Fig. 1
Fig. 1
Recruitment of patients into the study. All patients admitted to the ICU in the three participating centers from 24 February 2014 until 17 December 2014, in whom blood glucose control needed to be initiated, were screened for eligibility. This resulted in 1550 patients who were randomized and analyzed (923 patients after cardiac surgery and 627 patients for other reasons as predefined). All patients were included in the primary analysis. LOGIC-C patients randomized to algorithm-guided blood glucose control, Nurse-C patients randomized to blood glucose control by trained nurses
Fig. 2
Fig. 2
Blood glucose control and numbers of patients in the two randomized groups during the first 3 days in the ICU, per study center. Upper panels overall mean blood glucose levels (mg/dL) for both the algorithm-guided (dashed line) and the nurse-directed (solid line) blood glucose control group per center during the first 72 h in the ICU, which is the median ICU stay. The average blood glucose is computed over all glucose samples (per center) belonging to the previous 4-h time slot. The glycemic target range was 80–110 mg/dL for Leuven and Hasselt, unlike Amsterdam where the glycemic target range was 90–145 mg/dL. Lower panels the number of patients for the Nurse-C group (Nurse) (black bars) and LOGIC-C group (LOGIC) (gray bars)

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