Tight Glucose Control in Critically Ill Patients Using a Specialized Insulin- Nutrition Table Development Implementation of the SPRINT Protocol T. Lonergan, J.G. Chase, A. Le Compte, M. Willacy et al. Department of Mechanical Engineering Centre for Bio-Engineering University of Canterbury Christchurch, New Zealand

Overview Background – Stress-induced hyperglycaemia – Active Insulin Control (AIC) SPRINT – Introduction – Development Clinical Testing and Results

Background  Stress-Induced hyperglycaemia prevalent in critical care  Impaired endogenous insulin production  Increased effective insulin resistance  Average blood glucose values > 10mmol/L not uncommon in some critical care units (over length of stay)  Tight control  better outcomes :  Reduced mortality 27-43% ( mmol/L) [van den Berghe et al, 2001; Krinsley, 2004; …]  Reduced length of stay and length of mechanical ventilation Goal: Keep Blood Glucose ~Normal (4.0 – 6.0 mmol/L, 75 – 110 dg/mL)

AIC 5 Develop new protocol with same (or better) control Easy to implement in clinical environment Compare to international protocols Active Insulin Control Evolution AIC 4 Computerised Control Protocol  Insulin + Nutrition AIC 1 – 3 Development of Mathematical Model + 1 st Trials  Insulin-only

SPRINT Step 1 = Feed Rate Table Requires current glucose measurement and last hour change in glucose

SPRINT Step 2 = Insulin Table If feed rate = 0 use only insulin wheel Requires current glucose measurement, last hour change and last hours insulin bolus

Clinical Testing Virtual trials using fitted long term patient data to create virtual patient responses – Tests algorithms and methods safely – Provides insight into potential long term usage 33+ Clinical trials in Christchurch ICU – Clinical proof of concept – Ethical consent granted by Canterbury Ethics Committee – Process Improvement Change

Development & Protocol Comparison SPRINT Protocol AIC4 Protocol Mayo Clinic Protocol (Krinsley) Leuven Protocol (van den Berghe et al) Bath University Protocol Yale University Protocol CDHB Insulin Sliding Scale Protocol Aggressive Insulin Sliding Scale Protocol Insulin rate BG level Standard Aggressive < 4 mmol/L0 U/hr0 U/hr0 U/hr 4 – 5.9 mmol/L1 U/hr1 U/hr 6 – 7.9 mmol/L2 U/hr2 U/hr 8 – 9.9 mmol/L3 U/hr4 U/hr 10 – 11.9 mmol/L4 U/hr6 U/hr 12 – 13.9 mmol/L5 U/hr6 U/hr >= 14 mmol/L6 U/hr6 U/hr Goal #1 = SPRINT ≥ Best Clinical Practice Goal #2 = Effectiveness of AIC4 with ease of Leuven Protocol Use same virtual trial cohort as previously to test all protocols

Protocol Comparison Results 45% 25% Bad! Very Bad! Also Bad! Not Trying?

Clinical Results 4688 total hours of control 3578 measurements (47.4% two-hourly) Overall Average BG = 5.9 +/- 0.9 mmol/L Time in mmol/L = % Time in mmol/L = 86% Time in mmol/L = 94% Percentage of measurements < 4 mmol/L = 1.8% Percentage of measurements < 3 mmol/L = 0.0% Minimum 3.1 mmol/L Extremely tight control !

Clinical Results Average Insulin = 2.6 U/hr Average Feed = 62% = 1150 kcal/day!!!! – versus prior hospital rate of 58%! Age: Mean = 55, Range = APACHE II (Risk of Death) = 20 (36.7%) APACHE III = 58 SAPS II (Risk of Death) = 43 (33.3%) Mortality (at ICU discharge) = 24.2%

Conclusions Implemented tight glycaemic control into the ICU – Developed a simple, easy-to-use system: SPRINT – High compliance by clinical staff due to ease of use – Performance amongst the best in the world – 33+ patients and growing Clinical results match desired outcomes – Exceed published protocols by 3-5x on variation – Better average glucose for same or less insulin – Much more critically ill cohort

Acknowledgements Maths and Stats Gurus Dr Dom Lee Dr Bob Broughton Dr Chris Hann Prof Graeme Wake Thomas Lotz Jessica Lin & AIC3 AIC2 & Dr. G. Shaw Jason Wong & AIC4 The Danes Prof Steen Andreassen Dunedin Dr Kirsten McAuley Prof Jim Mann Assoc. Prof. Geoff Chase Aaron Le Compte Mike Willacy