Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial

Abstract

Introduction: Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol.

Methods: Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM.

Results: The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without hypoglycemia (<4 mM) during either therapy.

Conclusions: Fully automated closed-loop control based on subcutaneous glucose measurements is feasible and may provide efficacious and hypoglycemia-free glucose control in critically ill adults.

Trial registration: ClinicalTrials.gov Identifier, NCT01440842.

Figure 1

Components of the closed-loop glucose-control system.

Figure 2

User interface of the closed-loop system.

Figure 3

Cumulative distribution of reference glucose values obtained during closed-loop and local treatment protocol. Dashed vertical lines indicate the primary study target range from 6.0 to 8.0 mM. Vertical fine dashed lines indicate the wider target from 4.0 to 10.0 mM.

Figure 4

An example of the 48-hour closed-loop study. Darker red continuous line represents sensor glucose. Lighter red squares represent reference glucose measurements used for sensor calibration. Blue line represents insulin infusion. Thin red dashed lines indicate primary target. Dextrose infusion was not required in this study.

Figure 5

Mean reference glucose per subject during closed-loop (n = 12) and local treatment protocol (n = 12). Horizontal black line indicates the mean reference glucose in each intervention arm.

Figure 6

Glucose and insulin values during infusion. Top panel: Glucose profiles (median and interquartile range) during closed-loop and local treatment protocol. Bottom panel: Median insulin infusion rates during closed-loop and local treatment protocol. The dashed lines indicate the primary target range from 6 to 8 mM.