Evaluation and Enhancement of an Intraoperative Insulin Infusion Protocol via In-Silico Simulation

Abstract

Intraoperative glycemic control, particularly in cardiac surgical patients, remains challenging. Patients with impaired insulin sensitivity and/or secretion (i.e., type 1 diabetes mellitus) often manifest extremely labile blood glucose measurements during periods of stress and inflammation. Most current insulin infusion protocols are developed based on clinical experiences and consensus among a local group of physicians. Recent advances in human glucose metabolism modeling have established a computer model that invokes algorithms representing many of the pathways involved in glucose dysregulation for patients with diabetes. In this study, we used an FDA approved glucose metabolism model to evaluate an existing institutional intraoperative insulin infusion protocol via closedloop simulation on the virtual diabetic population that comes with the computer model. A comparison of simulated responses to actual retrospective clinical data from 57 type 1 diabetic patients undergoing cardiac surgery managed by the institutional protocol was performed. We then designed a proportional-derivative controller that overcomes the weaknesses exhibited by our old protocol while preserving its strengths. In-silico evaluation results show that our proportionalderivative controller more effectively manages intraoperative hyperglycemia while simultaneously reducing hypoglycemia and glycemic variability. By performing insilico simulation on intraoperative glucose and insulin responses, robust and seemingly efficacious algorithms can be generated that warrant prospective evaluation in human subjects. KeywordsIntraoperative glycemic control, in-silico evaluation, proportional-derivative controller, insulin infusion protocol, computer model Abstract-Intraoperative glycemic control, particularly in cardiac surgical patients, remains challenging. Patients with impaired insulin sensitivity and/or secretion (i.e., type 1 diabetes mellitus) often manifest extremely labile blood glucose measurements during periods of stress and inflammation. Most current insulin infusion protocols are developed based on clinical experiences and consensus among a local group of physicians. Recent advances in human glucose metabolism modeling have established a computer model that invokes algorithms representing many of the pathways involved in glucose dysregulation for patients with diabetes. In this study, we used an FDA approved glucose metabolism model to evaluate an existing institutional intraoperative insulin infusion protocol via closedloop simulation on the virtual diabetic population that comes with the computer model. A comparison of simulated responses to actual retrospective clinical data from 57 type 1 diabetic patients undergoing cardiac surgery managed by the institutional protocol was performed. We then designed a proportional-derivative controller that overcomes the weaknesses exhibited by our old protocol while preserving its strengths. In-silico evaluation results show that our proportional-derivative controller more effectively manag...

An Intraoperative Glucose Control Benchmark for Formal Verification

“…The PD controller (see Kohl et al (2013)) calculates the insulin or glucose dose based on two plasma glucose readings: the current value y(k) and the last reading y(k−1) sampled 30 minutes before; those are the same glucose inputs required by the IIP. The PD controller updates uc(k), ub(k), and m(k) based on y(k) and y(k − 1) according to the rules defined in Table 3.…”

“…In this section, we introduce the FDA-accepted T1DMS model (Man et al (2007); Dalla Man et al (2014)) modified for the intraoperative clinical scenario and a clinically validated glucose control protocol ( Kohl et al (2013)). …”

“…Our previous work identifies the weaknesses of the IIP and proposes a proportional-derivative (PD) controller that reduces intraoperative hypoglycemia while preserving the IIP's strengths in simulation studies. The clinicians who developed the IIP believed that the results warrant prospective in-vivo evaluations of the PD controller (Kohl et al (2013)). …”

“…Our team has collaborated with clinicians in the Division of Critical Care at the Hospital of the University of Pennsylvania in order to evaluate an intraoperative insulin protocol (IIP) that manages the glucose level for cardiac surgery patients (Kohl et al (2013)). Our previous work identifies the weaknesses of the IIP and proposes a proportional-derivative (PD) controller that reduces intraoperative hypoglycemia while preserving the IIP's strengths in simulation studies.…”

“…Data suggests that specialized inpatient glucose level management within a safe range can minimize the hypoglycemia risk and improve clinical outcomes (Subramaniam et al (2009); Lazar et al (2004)). Clinicians currently follow rule-based protocols to administer insulin and glucose during surgeries (e.g., see Kohl et al (2013)), but those protocols are still far from foolproof (Meijering et al (2006)). Thus, verifying that intraoperative glycemic controllers avoid severe hypoglycemia/hyperglycemia events across a diabetic population is imperative.…”