Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose?

Objective: Studies showing improved outcomes with tight glycemic control in the intensive care unit (ICU) have resulted in a substantial number of new insulin delivery algorithms being proposed. The present study highlights mechanisms used in the better-known approaches, examines what might be critical differences among them, and uses systems theory to characterize the conditions under which each can be expected to perform best. Methods: Algorithm dose (ΔI/ΔG) and step (response to a persistent elevation in glucose) response curves were calculated for written instruction algorithms, developed at the Providence Heart and Vascular Institute (Portland [P] protocol), the University of Washington (UW), and Yale University (Y), together with similar curves for the Glucommander (GM) and proportional integral derivative (PID) computer algorithms. From the simulated curves, different mechanisms used to adjust insulin delivery were identified. Results: All algorithms increased insulin delivery in response to persistent hyperglycemia, but the mechanism used altered the algorithm's sensitivity to glucose, or gain, in the GM, UW, and Y protocols, while leaving it unchanged for the P protocol and PID algorithm. Conclusions: The increase in insulin delivery in response to persistent hyperglycemia observed with all the algorithms can be expected to bring subjects who respond to insulin to targeted glucose ranges. However, because the PID and P protocols did not alter the insulin delivery response curves, these algorithms can be expected to take longer to achieve target glucose levels in individuals who are insulin resistant and/or are exposed to increased carbohydrate loads (e.g., glucose infusions). By contrast, the GM, UW, and Y algorithms can be expected to adapt to the insulin resistance such that the time to achieve target levels is unchanged if the time for insulin to act does not change. If the insulin resistance is accompanied by a longer time for insulin to act, the UW, Y, and GM algorithms may increase the risk of hypoglycemia. Under these conditions, the longer time required for the PID and P protocols to achieve a target glucose level may be a reasonable trade-off for no increase in the risk of hypoglycemia.

[1]  D. Elahi In Praise of the Hyperglycemic Clamp: A method for assessment of β-cell sensitivity and insulin resistance , 1996, Diabetes Care.

[2]  R S Parker,et al.  The intravenous route to blood glucose control. , 2001, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[3]  B Wayne Bequette,et al.  Analysis of Algorithms for Intensive Care Unit Blood Glucose Control , 2007, Journal of diabetes science and technology.

[4]  Malgorzata E. Wilinska,et al.  Tight glycaemic control by an automated algorithm with time-variant sampling in medical ICU patients , 2008, Intensive Care Medicine.

[5]  J. Halter,et al.  Potentiation of insulin secretory responses by plasma glucose levels in man: evidence that hyperglycemia in diabetes compensates for imparied glucose potentiation. , 1979, The Journal of clinical endocrinology and metabolism.

[6]  M. Molitch,et al.  Inpatient management of hyperglycemia: the Northwestern experience. , 2006, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[7]  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.

[8]  G M Steil,et al.  Modeling insulin action for development of a closed-loop artificial pancreas. , 2005, Diabetes technology & therapeutics.

[9]  Liu Xinbing,et al.  Intensive insulin therapy for the critically ill patients with stress hyperglycemia , 2008 .

[10]  Bruce Buckingham,et al.  Glucose control in pediatric intensive care unit patients using an insulin-glucose algorithm. , 2007, Diabetes technology & therapeutics.

[11]  Bruce W Bode,et al.  Glucommander: a computer-directed intravenous insulin system shown to be safe, simple, and effective in 120,618 h of operation. , 2005, Diabetes care.

[12]  J. Weinreb,et al.  Intensive Insulin Therapy in Critical Care , 2007, Diabetes Care.

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

[14]  Yingxing Wu,et al.  Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project. , 2004, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[15]  S. Braithwaite,et al.  Description and evaluation of a glycemic management protocol for patients with diabetes undergoing heart surgery. , 2002, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[16]  R. Bergman,et al.  Accurate Assessment of β-Cell Function: The Hyperbolic Correction , 2002 .

[17]  James D Dziura,et al.  Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. , 2004, Diabetes care.

[18]  R. Bergman,et al.  Accurate assessment of beta-cell function: the hyperbolic correction. , 2002, Diabetes.

[19]  Katsuhiko Ogata,et al.  Modern control engineering (3rd ed.) , 1996 .

[20]  Malgorzata E. Wilinska,et al.  Intensive insulin therapy: enhanced Model Predictive Control algorithm versus standard care , 2008, Intensive Care Medicine.

[21]  Andrea Tura,et al.  Assessing insulin secretion by modeling in multiple-meal tests: role of potentiation. , 2002, Diabetes.

[22]  P. Davidson,et al.  Improving Hyperglycemia Management in the Intensive Care Unit , 2006, The Diabetes educator.

[23]  Irl B Hirsch,et al.  The rationale and management of hyperglycemia for in-patients with cardiovascular disease: time for change. , 2003, The Journal of clinical endocrinology and metabolism.

[24]  H. Tymkew,et al.  A randomized study in diabetic patients undergoing cardiac surgery comparing computer-guided glucose management with a standard sliding scale protocol. , 2008, Journal of cardiothoracic and vascular anesthesia.

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