Tight Glucose Control in Critically Ill Patients Using

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 > 10 mmol/L not uncommon in some critical care units (over length of stay) § Tight control better outcomes: § Reduced mortality 27 -43% (4. 0 -7. 75 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/m. L)

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

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 AIC 4 Protocol Mayo Clinic Protocol (Krinsley) • Goal #1 = SPRINT ≥ Best Clinical Practice • Goal #2 = Effectiveness of AIC 4 with ease of Leuven Protocol (van den Berghe et al) Bath University Protocol Yale University Protocol CDHB Insulin Sliding Scale Protocol Aggressive Insulin Sliding Scale Protocol • Use same virtual trial cohort as previously to test all protocols Insulin rate BG level Standard Aggressive < 4 mmol/L 0 U/hr 4 – 5. 9 mmol/L 1 U/hr 6 – 7. 9 mmol/L 2 U/hr 8 – 9. 9 mmol/L 3 U/hr 4 U/hr 10 – 11. 9 mmol/L 4 U/hr 6 U/hr 12 – 13. 9 mmol/L 5 U/hr 6 U/hr >= 14 mmol/L 6 U/hr

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 4 -6. 1 mmol/L = 59. 363% Time in 4 -7. 0 mmol/L = 86% Time in 4 -7. 75 mmol/L = 94% Extremely tight control ! • Percentage of measurements < 4 mmol/L = 1. 8% • Percentage of measurements < 3 mmol/L = 0. 0% • Minimum 3. 1 mmol/L

Clinical Results • Average Insulin = 2. 6 U/hr • Average Feed = 62% = 1150 kcal/day!!!! – versus prior hospital rate of 58%! • Age: Mean = 55, Range = 27 -84 • • 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 -5 x on variation – Better average glucose for same or less insulin – Much more critically ill cohort

Acknowledgements Jessica Lin & AIC 3 Thomas Lotz Assoc. Prof. Geoff Chase Jason Wong & AIC 4 Dunedin Dr Kirsten Mc. Auley AIC 2 & Dr. G. Shaw Mike Willacy Aaron Le Compte The Danes Prof Steen Andreassen Prof Jim Mann Maths and Stats Gurus Dr Dom Lee Dr Bob Broughton. Prof Graeme Wake Dr Chris Hann