Introduction Stress-induced hyperglycaemia is prevalent in critical care. Control of blood glucose levels to within a 4.4 to 6.1 mmol/L range or below 7.75 mmol/L can reduce mortality and improve clinical outcomes. The Specialised Relative Insulin Nutrition Tables (SPRINT) protocol is a simple wheel-based system that modulates insulin and nutritional inputs for tight glycaemic control.

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Targeted, tight model-based glycemic control in critical care patients that can reduce mortality 18 -45% is enabled by prediction of insulin sensitivity, S I . However, this parameter can vary significantly over a given hour in the critically ill as their condition evolves. A stochastic model of S I variability is constructed using data from 165 critical care patients. Given S I for an hour, the stochastic model returns the probability density function of S I for the next hour. Consequently, the glycemic distribution following a known intervention can be derived, enabling pre-determined likelihoods of the result and more accurate control.Cross validation of the S I variability model shows that 86.6% of the blood glucose measurements are within the 0.90 probability interval, and 54.0% are within the interquartile interval. "Virtual Patients" with S I behaving to the overall S I variability model achieved similar predictive performance in simulated trials (86.8% and 45.7%).Finally, adaptive control method incorporating S I variability is shown to produce improved glycemic control in simulated trials compared to current clinical results. The validated stochastic model and methods provide a platform for developing advanced glycemic control methods addressing critical care variability.

ARTICLE IN PRESSCOMM 2642 1-11 c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e x x x( 2 0 0 7 ) xxx-xxx j o u r n a l h o m e p a g e : w w w . i n t l . e l s e v i e r h e a l t h . c o m / j o u r n a l s / c m p b The proposed protocol is simple, cost effective, repeatable and highly correlated to the gold-standard clamp. Monte

Intensive insulin therapy (IIT) and tight glycaemic control (TGC), particularly in intensive care units (ICU), are the subjects of increasing and con-