Tight Glucose Control in Tight Glucose Control in Critically Ill Patients Using a Critically Ill Patients Using a Specialized Insulin-Nutrition Specialized Insulin-Nutrition

TableTable

Development Implementation of the SPRINT Protocol

T. Lonergan, J.G. Chase, A. Le Compte, M. Willacy et al.

Department of Mechanical EngineeringCentre for Bio-EngineeringUniversity of Canterbury

Christchurch, New Zealand

OverviewOverview

• Background– Stress-induced hyperglycaemia– Active Insulin Control (AIC)

• SPRINT– Introduction– Development

• Clinical Testing and Results

BackgroundBackground

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% (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/mL)

AIC 5

• Develop new protocol with same (or better) control

• Easy to implement in clinical environment

• Compare to international protocols

Active Insulin Control Active Insulin Control EvolutionEvolution

AIC 4 Computerised Control Protocol

Insulin + Nutrition

AIC 1 – 3 Development of Mathematical Model + 1st Trials

Insulin-only

SPRINT Step 1 = Feed Rate SPRINT Step 1 = Feed Rate Table Table

Requires current glucose measurement and last hour change in glucose

SPRINT Step 2 = Insulin TableSPRINT 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 TestingClinical 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 Development & Protocol ComparisonComparison

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/L 0 U/hr 0 U/hr 0 U/hr

4 – 5.9 mmol/L 1 U/hr 1 U/hr

6 – 7.9 mmol/L 2 U/hr 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 6 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

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0 2 4 6 8 10 12 14 16 18 20

Blood glucose level [mmol/L]

Den

sity

of

mea

sure

men

ts

SPRINT

AIC4

Bath

Leuven

Mayo Clinic

Yale

Sliding Scale

Aggressive sliding scale

Protocol Comparison Protocol Comparison ResultsResults

45%

25%

Bad!

VeryBad!

Also Bad!

Not Trying?

Clinical ResultsClinical 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%

• 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 ResultsClinical 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%

ConclusionsConclusions• 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

AcknowledgementsAcknowledgements

Maths and Stats Gurus

Dr Dom LeeDr Bob Broughton Dr Chris Hann

Prof Graeme Wake

Thomas LotzJessica 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