Roosmarijn T. M. van Hooijdonk

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. 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. 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). 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. ClinicalTrials.gov, NCT02056353 . Registered on 4 February 2014.

Background Point-of-care testing of blood glucose (BG-POCT) is essential for safe and effective insulin titrations in critically ill patients under glucose control with insulin. The costs associated with this practice are considered substantial, especially when more frequent blood glucose (BG) testing is needed, as with more strict glucose control (SGC) aiming for lower BG levels. Objective The objective of this study was to estimate, from a hospital perspective, the incremental cost effectiveness of an SGC guideline, aiming for BG levels of 4.4-6.1 mmol/L, compared to the situation before implementation of that guideline (aiming for BG levels 6.1 mmol/L), 'hypoglycaemia' (defined as BG levels <4.4 mmol/L) and 'in-hospital death' was developed to compare expected costs, number of patients within target and number of life-years saved before and after implementation of the SGC guideline. The effectiveness estimates are based on empirical data from 3195 patients 12 and 24 months before and after implementation of the guideline, respectively. All costs have been converted to price year 2013, and are estimated based on hospital data, the literature and available price lists. Results The number of BG POCT increased from 4.8 [interquartile range (IQR) 2.6-6.7] to 8.0 [IQR 4.1-11.2] per patient per day, accruing 58 % higher costs for BG POCT (13.56 vs. 8.57 per patient) in the SGC protocol versus the situation before implementation. When taking total hospital costs and clinical effects into account, implementation of the SGC guideline increased total hospital costs per patient by 1.8 %, i.e. 355 (from 20,617 to 20,972) during the inpatient stay, while the number of patients in target glucose levels increased by 1.4 % (i.e. from 881 to 895 per 1000 patients). This translates to an incremental cost-effectiveness ratio of 25 per additional patient within the target glucose level. The model outcomes are most sensitive to changes in ICU length of stay. Conclusion The increase in the number of patients and time within target glucose levels is achieved with a small increase in total direct hospital cost

Introduction: There is a need for continuous glucose monitoring in critically ill patients. The objective of this trial was to determine the point accuracy and reliability of a device designed for continuous monitoring of interstitial glucose levels in intensive care unit patients. Methods: We evaluated point accuracy by comparing device readings with glucose measurements in arterial blood by using blood gas analyzers. Analytical and clinical accuracy was expressed in Bland-Altman plots, glucose prediction errors, and Clarke error grids. We used a linear mixed model to determine which factors affect the point accuracy. In addition, we determined the reliability, including duration of device start-up and calibration, skips in data acquisition, and premature disconnections of sensors. Results: We included 50 patients in whom we used 105 sensors. Five patients from whom we could not collect the predefined minimum number of four consecutive comparative blood draws were excluded from the point accuracy analysis. Therefore, we had 929 comparative samples from 100 sensors in 45 patients (11 (7 to 28) samples per patient) during 4,639 hours (46 (27 to 134) hours per patient and 46 (21 to 69) hours per sensor) for the accuracy analysis. Point accuracy did not meet the International Organization for Standardization (ISO) 14971 standard for insulin dosing accuracy but did improve with increasing numbers of calibrations and was better in patients who did not have a history of diabetes. Out of 105 sensors, 60 were removed prematurely for a variety of reasons. The device start-up time was 49 (43 to 58) minutes. The number of skips in data acquisition was low, resulting in availability of real-time data during 95% (89% to 98%) of the connection time per sensor. Conclusions: The point accuracy of a device designed for continuous real-time monitoring of interstitial glucose levels was relatively low in critically ill patients. The device had few downtimes, but one third of the sensors were removed prematurely because of unresolved sensor- or device-related problems. Trial registration: Netherlands Trial Registry number: NTR3827. Registered 30 January 2013.

In critically ill patients, glucose control with insulin mandates time– and blood–consuming glucose monitoring. Blood glucose level fluctuations are accompanied by metabolomic changes that alter the composition of volatile organic compounds (VOC), which are detectable in exhaled breath. This review systematically summarizes the available data on the ability of changes in VOC composition to predict blood glucose levels and changes in blood glucose levels.