Use of an intravascular continuous blood glucose sensor during post operative icu care of cardiac surgery patients K. Prasada, P. Gopalb, B. Cranec, A. Mackenziec and N. Barwellc Contact email address: bcrane@glysure.com Introduction Close monitoring and control of blood glucose concentrations within defined limits has been advocated for all ICU patients, a practice referred to as Tight Glycaemic Control (TGC). Several clinical studies have demonstrated that there is a close correlation between control of blood glucose concentrations and improved clinical outcomes.1-4 Van den Berghe's research, involving post operative cardiac surgery patients, showed highly variable blood glucose concentrations which reinforced the need for a continuous blood glucose monitoring system. Recent research has showed an association between both hypoglycemic events and glucose variability and mortality has increased the need for continuous systems which can provide early warnings of hypoglycaemia and effectively measure variability.5-8 GlySure Limited has developed an intravascular glucose monitoring system to simplify the application of hospital protocols for TGC at the point of care. The GlySure Continuous Glucose Monitoring System comprises two main parts, a monitor and a sterile sensor set which includes an integrated fiber-optic sensor/introducer and a fully automated calibration module. The continuous glucose sensor contains a fluorescent glucose receptor, which produces a signal that is proportional to the glucose concentration in the patient's blood. The reversible nature of the glucose-receptor interaction enables monitoring without the consumption of the patient’s glucose. The CGM sensor is placed in intensive care patients via a central venous catheter (CVC).  As central venous access is required on nearly all ICU patients, the sensor does not require any additional access lines. Method The study used GlySure sterile, single use sensors and monitor systems to measure the blood glucose concentration in 24 ICU patients continuously and in real time. Before use each sensor was calibrated using the GlySure software controlled calibration system which calibrates the sensor whilst maintaining sensor sterility. A custom made 5 lumen CVC, 9.5 Fr CVC, device allowed the fluorescence optical based sensor to be placed into the patient’s right internal jugular vein through a dedicated proximal lumen of the catheter. The other 4 lumens were used for sampling or infusions. Blood samples were taken at regular intervals and the glucose concentration was measured on a Yellow Spring Instrument [YSI]. At the time of sampling the monitor was time stamped to allow subsequent statistical analysis between the continuous GlySure sensor and the intermittent YSI values. Administration of drugs and other therapies were also time stamped on the monitor such that any interference to the sensor performance by the administration of these therapies could be detected. Monitoring ceased when indicated by the patients condition or removal from the ICU. Figure 3. Customised 5 lumen CVC Figure 1. Schematic showing the system configuration Latest clinical data The data presented here are from 24 recent cardiac patients during postoperative ICU care. The patients were all between 27 and 72 years old and underwent either a coronary artery bypass graft (CABG) or mitral valve repair (MVR). The full breakdown of patient profiles is shown in Table 1. Data from recent clinical trials; A shows the data from a patient that had undergone a CABG procedure and was diabetic; B shows the data from a patient that had undergone a CABG+IABP procedure and was both diabetic and hypertensive. Figure 6. Average Min Max Male % 75 Age 56.1 24 72 Height 162.7 146 174 Weight 67.1 34 86 BMI / kg.m-2 25.4 15.95 33.69 Runtime 49.0 21.6 88.3 A B Table 1. Patient Statistics Matched pairs of data from the 24 patients are shown on a Clark Error Grid (Figure 4). 99.5% of the data fell within the A+B region and 92.7% fell within region A . The MARD was calculated to be 7.70%. The sensors monitored the patient's blood glucose levels for the entirety of the stay in the ICU. The MARD, from the 24 patients combined, was analysed vs. time (Figure 5 and Table 3). Over a period of 3 days the average MARD is fairly consistent, rising from 3.76% for the first day of monitoring to 9.42% for the third day of monitoring. These figures indicate that the sensor is not being temporally affected by being placed in vivo. Figure 4. Combined Clark Error Grid Figure 5. MARD vs. Time Day n MARD Mean Min Max 1 208 6.93 3.76 12.92 2 115 8.06 0.18 15.04 3 19 11.45 9.42 13.41 Table 3. Combined MARD vs. Time Conclusions The results demonstrate good correlation with the accepted standard of blood glucose determination in ICU practice. This can dramatically reduce need for frequent intermittent sampling and early prediction of hypoglycemic excursions. GlySure’s continuous intravascular glucose sensor could enable Safe, Accurate, Fast and Effective (S.A.F.E.) implementation of TGC protocols and trending. References/Acknowledgements 1. G. Van den Berghe, NEJM, 2001, 345, 19, 1359-1367. 2. G. Van den Berghe, Crit. Care. Med., 2003, 2, 359-66. 3. G. Van den Berghe, J. Clin. Invest., 2004, 1114, 1187-1195. 4. J.S. Krinsley, Mayo. Clin. Proc., 2004, 79, 992-1000. 5. M. Egi, R. Bellomo, E. Stachowski, C.J. French, G. Hart, Anesthesiology, 2006, 105, 244–252. 6. I. Mackenzie, T. Whitehouse, P. Nightingale, Intensive Care Med., 2011, 37, 3, 435-443. 7. J.S. Krinsley, Crit. Care Med., 2008, 36, 3008–3013. 8. J.S. Krinsley, Critical Care, 2011, 15, R173. aCare Hospitals, Hyderabad, India. bApollo Hospitals, Hyderabad, India. cGlySure Ltd, Abingdon, UK.