EAGER: Insulin Delivery for Diabetes Management in the Intensive Care Unit as a Feedback Control Problem

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0938288-GrizzleDiabetes impacts more than 30% of hospitalized patients. Currently, management protocols for monitoring blood glucose in the hospital setting are overly simplistic and often ineffective. An interdisciplinary team consisting of a diabetologist/endocrinologist and a control engineer seeks to improve the regulation of blood glucose levels in patients in the intensive care setting, especially those who are there postoperatively. The current insulin dosing protocols are actually feedback control algorithms for blood glucose levels, but little work has been done to analyze them as such. The central theme of this proposal is that feedback control techniques can lead to better performing and safer insulin dosing protocols. The PIs will build and validate a dynamic model of blood glucose response to intravenous insulin infusion rate that is adapted to various classes of patients seen in the ICU. The model will be based on patient data and will account for important perturbing factors such as dextrose infusion rates, nutrition (oral and parenteral), insulin resistant or sensitizing drugs, patient body temperature and clinical severity when entering the ICU. They will perform an extensive control analysis of existing insulin infusion protocols in closed-loop with the obtained dynamic model, with an emphasis on studying their nominal response as well as their response to a wide range of model parameter variations. On the basis of the model building and closed-loop control analysis performed above, the PIs will propose improvements to the existing protocols, including the so-called paper protocols that are employed in hospitals worldwide, which reflect a superior control law.Intellectual Merit: There have been no published comparisons of various protocols for such factors as rapidity and consistency of reaching targets or frequency of hypoglycemia. Neither has there been a systematic study of robustness of the existing protocols to patient variations such as nutrition (especially carbohydrates), changing vasopressors, steroids and other drugs. Published protocols claim between 46 to 69 % of blood glucose levels reach goal. Hypoglycemia rates can range from 0.3 to 15 % in several studies. A protocol that could bring blood glucose levels to goal quickly, respond appropriately and in a timely manner to changing insulin resistance/sensitivity, and address meals and drug regimes would have a significant impact on patient care. Preempting hypoglycemia by automatically noting the changing insulin sensitivity could address the fear of low blood glucose levels. In an unresponsive sedated patient, this would help minimize the concern for hypoglycemia which is the biggest barrier to the use of insulin. Lastly the ideal protocol in addition to addressing all the above issues would allow the health care provider to titrate a different blood glucose range and sensitivity for patients in different ICU settings (medical, surgical, cardiac, or trauma burn), minimize blood glucose swings with meals or infusions containing dextrose, and prevent hypoglycemia. The work proposed here will take us a significant step toward this goal.Broader Impacts: The general principles developed by this research should be transferable to the outpatient management of diabetes where the scope is of an enormous magnitude and a variety of other settings, including anesthesia and pain management.