Continuous Glucose Monitors and the Burden of Tight Glycemic Control in Critical Care: Can They Cure the Time Cost?

Background: Tight glycemic control (TGC) in critical care has shown distinct benefits but has also proven to be difficult to obtain. The risk of severe hypoglycemia (<40 mg/dl) raises significant concerns for safety. Added clinical burden has also been an issue. Continuous glucose monitors (CGMs) offer frequent automated measurement and thus the possibility of using them for early detection and intervention of hypoglycemic events. Additionally, regular measurement by CGM may also be able to reduce clinical burden. Aim: An in silico study investigates the potential of CGM devices to reduce clinical effort in a published TGC protocol. Methods: This study uses retrospective clinical data from the Specialized Relative Insulin Nutrition Titration (SPRINT) TGC study covering 20 patients from a benchmark cohort. Clinically validated metabolic system models are used to generate a blood glucose (BG) profile for each patient, resulting in 33 continuous, separate BG episodes (6881 patient hours). The in silico analysis is performed with three different stochastic noise models: Two Gaussian and one first-order autoregressive. The noisy, virtual CGM BG values are filtered and used to drive the SPRINT TGC protocol. A simple threshold alarm is used to trigger glucose interventions to avert potential hypoglycemia. The Monte Carlo method was used to get robust results from the stochastic noise models. Results: Using SPRINT with simulated CGM noise, the BG time in an 80–110 mg/dl band was reduced no more than 4.4% to 45.2% compared to glucometer sensors. Antihypoglycemic interventions had negligible effect on time in band but eliminated all recorded hypoglycemic episodes in these simulations. Assuming 4–6 calibration measurements per day, the nonautomated clinical measurements are reduced from an average of 16 per day to as low as 4. At 2.5 min per glucometer measurement, a daily saving of ~25–30 min per patient could potentially be achieved. Conclusions: This paper has analyzed in silico the use of CGM sensors to provide BG input data to the SPRINT TGC protocol. A very simple algorithm was used for early hypoglycemic detection and prevention and tested with four different-sized intravenous glucose boluses. Although a small decrease in time in band (still clinically acceptable) was experienced with the addition of CGM noise, the number of hypoglycemic events was reduced. The reduction to time in band depends on the specific CGM sensor error characteristics and is thus a trade-off for reduced nursing workload. These results justify a pilot clinical trial to verify this study.

[1]  G. Van den Berghe,et al.  Intensive insulin therapy in the medical ICU. , 2006, The New England journal of medicine.

[2]  Deborah J. Cook,et al.  Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data , 2009, Canadian Medical Association Journal.

[3]  James D Dziura,et al.  Experience with the continuous glucose monitoring system in a medical intensive care unit. , 2004, Diabetes technology & therapeutics.

[4]  Christopher E. Hann,et al.  Model-based glycaemic control in critical care - A review of the state of the possible , 2006, Biomed. Signal Process. Control..

[5]  Christopher E. Hann,et al.  Stochastic modelling of insulin sensitivity and adaptive glycemic control for critical care , 2008, Comput. Methods Programs Biomed..

[6]  J Geoffrey Chase,et al.  A Benchmark Data Set for Model-Based Glycemic Control in Critical Care , 2008, Journal of diabetes science and technology.

[7]  Claudio Cobelli,et al.  The hot IVGTT two-compartment minimal model: indexes  of glucose effectiveness and insulin sensitivity. , 1997, American journal of physiology. Endocrinology and metabolism.

[8]  Marcus J. Schultz,et al.  Tight glycaemic control: a survey of intensive care practice in the Netherlands , 2006, Intensive Care Medicine.

[9]  Christopher E. Hann,et al.  Integral-based filtering of continuous glucose sensor measurements for glycaemic control in critical care , 2006, Comput. Methods Programs Biomed..

[10]  C. Strange,et al.  Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit* , 2006, Critical care medicine.

[11]  Boris Kovatchev,et al.  Evaluating the clinical accuracy of two continuous glucose sensors using continuous glucose-error grid analysis. , 2005, Diabetes care.

[12]  Pascale Carayon,et al.  A human factors engineering conceptual framework of nursing workload and patient safety in intensive care units. , 2005, Intensive & critical care nursing.

[13]  J. Geoffrey Chase,et al.  Impact of Human Factors on Clinical Protocol Performance: A Proposed Assessment Framework and Case Examples , 2008, Journal of diabetes science and technology.

[14]  R. Hovorka,et al.  Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT. , 2002, American journal of physiology. Endocrinology and metabolism.

[15]  D. Klonoff Continuous glucose monitoring: roadmap for 21st century diabetes therapy. , 2005, Diabetes care.

[16]  F. Chee,et al.  Expert PID control system for blood glucose control in critically ill patients , 2003, IEEE Transactions on Information Technology in Biomedicine.

[17]  B. Bistrian,et al.  Hyperglycemia and infection: which is the chicken and which is the egg? , 2001, JPEN. Journal of parenteral and enteral nutrition.

[18]  Boris Kovatchev,et al.  Analysis, Modeling, and Simulation of the Accuracy of Continuous Glucose Sensors , 2008, Journal of diabetes science and technology.

[19]  J. Krinsley,et al.  Glycemic variability: A strong independent predictor of mortality in critically ill patients* , 2008, Critical care medicine.

[20]  Ben Zarzaur,et al.  Performance of a dose-defining insulin infusion protocol among trauma service intensive care unit admissions. , 2006, Diabetes technology & therapeutics.

[21]  V. Gracias,et al.  Glycemic control needs a standard reference point. , 2006, Critical care medicine.

[22]  A. Malhotra,et al.  Stress-induced hyperglycemia. , 2001, Critical care clinics.

[23]  T. Evans,et al.  Glucose control and mortality in critically ill patients. , 2004, JAMA.

[24]  Iain Mackenzie,et al.  Tight glycaemic control: a survey of intensive care practice in large English hospitals , 2005, Intensive Care Medicine.

[25]  F. Chee,et al.  Closed-loop glucose control in critically ill patients using continuous glucose monitoring system (CGMS) in real time , 2003, IEEE Transactions on Information Technology in Biomedicine.

[26]  Thomas Lotz,et al.  A simple insulin-nutrition protocol for tight glycemic control in critical illness: development and protocol comparison. , 2006, Diabetes technology & therapeutics.

[27]  A. Kitabchi,et al.  Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. , 2002, The Journal of clinical endocrinology and metabolism.

[28]  Rinaldo Bellomo,et al.  Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients , 2006, Anesthesiology.

[29]  Iain Mackenzie,et al.  Hypoglycemia and cardiac arrest in a critically ill patient on strict glycemic control. , 2006, Anesthesia and analgesia.

[30]  James Stephen Krinsley,et al.  Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. , 2003, Mayo Clinic proceedings.

[31]  James Stephen Krinsley,et al.  Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. , 2004, Mayo Clinic proceedings.

[32]  H. Gerstein,et al.  Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview , 2000, The Lancet.

[33]  Jaap E Tulleken,et al.  Towards a feasible algorithm for tight glycaemic control in critically ill patients: a systematic review of the literature , 2006, Critical care.

[34]  M Schetz,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[35]  Geoffrey M. Shaw,et al.  Hypoglycemia Detection in Critical Care Using Continuous Glucose Monitors: An in Silico Proof of Concept Analysis , 2010, Journal of diabetes science and technology.

[36]  Christopher E. Hann,et al.  Stochastic modelling of insulin sensitivity variability in critical care , 2006, Biomed. Signal Process. Control..

[37]  B.W. Bequette,et al.  A Dual-Rate Kalman Filter for Continuous Glucose Monitoring , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[38]  Stephane Heritier,et al.  Intensive versus conventional glucose control in critically ill patients. , 2009, The New England journal of medicine.

[39]  J Geoffrey Chase,et al.  Model-based insulin and nutrition administration for tight glycaemic control in critical care. , 2007, Current drug delivery.

[40]  David C Klonoff,et al.  A review of continuous glucose monitoring technology. , 2005, Diabetes technology & therapeutics.

[41]  B A Mizock,et al.  Alterations in fuel metabolism in critical illness: hyperglycaemia. , 2001, Best practice & research. Clinical endocrinology & metabolism.

[42]  B. Bistrian,et al.  Intensive insulin therapy in critically ill patients. , 2002, The New England journal of medicine.