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LOGIC-InsulinBlood glucose control in the intensive care unit

Tom Van Herpe, PhD

tom.vanherpe@esat.kuleuven.be

+32 (0) 16 340987

Intensive Care Unit

• Hyperglycaemia(independent of diabetes)

• > 4 mio patients/y(USA and Europe)

• Increased mortality risk & complications

• Quality indicator in many countries

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Tight Glucose Control (TGC) in the ICU

• 3 clinical studies in Leuven:

• TGC lowers mortality (surgical ICU: 8.0% � 4.6%)1

• TGC lowers complications (e.g. blood stream infections: -46%)1

• TGC lowers costs (surgical ICU: -2638 € per patient)2

• Expert-nurse-driven TGC

1 Van den Berghe et al. New England Journal of Medicine 20012 Van den Berghe et al. Critical Care Medicine 2006

• Clinical community: sensor + algorithm

• Clinical studies outside Leuven: mixed findings• TGC increases mortality 3

• TGC ‘looks’ unsafe (increase of hypoglycaemia episodes)

3 Finfer et al. New England Journal of Medicine 2009

Blood glucose control in the ICU

Glucose sensor

Glycaemia control system

Patient

Insulin delivery Complex

interplay

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LOGIC-Insulin

Why LOGIC-Insulin?

• ‘Leuven’ nurses into an algorithm

• Modifiable blood glucose target range

• Patent protected algorithm (EU + USA)

• Very user-friendly graphical user interface

• … and clinically validated !

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Clinical validation of LOGIC-Insulin

1. Randomized Controlled Trial 1 (single-centre)

• Patient recruitment from 22 August to 16 December 2011� 300 patients

� Heterogeneous mix (surgical and medical ICU)

• Written informed consent within 24h after admission

• Random allocation:� Nurse-Controlled

� LOGIC-Controlled

• Tight Glycemic Control (TGC): 80–110 mg/dL

• TGC discontinued when:� Start oral intake

� At discharge

� No arterial line

� Switch to palliative care

� Recurrent severe hypoglycemia (< 40 mg/dL)

• Max study duration = 14 days

Clinical validation of LOGIC-Insulin

1. Randomized Controlled Trial 1 (single-centre)• Blood glucose:

� Arterial line

� Blood gas analyser (ABL 700, Radiometer)

• Nutrition:� No change in treatment

• LOGIC-Controlled patient group:

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Clinical validation of LOGIC-Insulin

1. Randomized Controlled Trial 1 (single-centre)

Nurse

controlled

LOGIC-Insulin

controlled

Patients 151 149

Age Mean (std) 62 (14) 65 (15)

GenderMale

Female

93 (62%)

58 (38%)

88 (59%)

61 (41%)

BMI (kg/m2) Mean (std) 25.9 (4.8) 26.5 (5.5)

DiabetesNo

Yes

119 (78.8%)

32 (21.2%)

117 (78.5%)

32 (21.5%)

APACHE II Median (IQR) 24 (10) 23 (10)

Admission type

Post-cardiac surgery - N (%)

Transplantation - N (%)

Medical - N (%)

Other surgery - N (%)

74 (49.0%)

25 (16.6%)

23 (15.2%)

29 (19.2%)

76 (51.0%)

19 (12.8%)

26 (17.4%)

28 (18.8%)

Clinical validation of LOGIC-Insulin

1. Randomized Controlled Trial 1 (single-centre)• 300 patients

• More efficient and safer glucose control than Leuven nurses

• Van Herpe et al. Diabetes Care 2013

LOGIC-ControlledExpert nurses

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Nurse

controlled

LOGIC-Insulin

controlledP-value

Patients 151 149

Study period Median (IQR) 1.9 (1.1-3.7) days 1.9 (1.2-4.7) days P=0.42

Efficacy

Blood glucoseMean (std)

MinMax

107 (11) mg/dL28 mg/dL328 mg/dL

106 (9) mg/dL45 mg/dL

272 mg/dL

P=0.36

Glycemic Penalty Index

[Ideally < 23]Median (IQR) 12.4 (8.2-18.5) 9.8 (6.0-14.5) P<0.0001

Hyperglycemic Index

[Ideally < 10 mg/dl]Median (IQR) 4.2 (1.5-7.4) mg/dL 2.5 (1.2-4.4) mg/dL P=0.0028

Time in Target Mean (std) 60.1 (18.8) % 68.6 (16.7) % P=0.00016

Time to Reach Target Median (IQR) 2.9 (1.0-6.2) h 1.9 (0-3.8) h P=0.0035

Mean of Maximum Delta

Glycemia per day Median (IQR) 37 (27-46) mg/dL 31 (24-45) mg/dL P=0.045

Safety

Hypoglycemia

(patient)

# (%) of patients with at least 1 hypo

< 70 mg/dL< 60 mg/dL< 40 mg/dL

73 (48.3 %)27 (17.9 %)

5 (3.3 %)

48 (32.2 %)21 (14.1 %)

0 (0 %)

P=0.0048P=0.43

P=0.060

Hypoglycemia (samples)

# glycemia < 70 mg/dL# glycemia < 60 mg/dL# glycemia < 40 mg/dL

170 (3.8 %)52 (1.2%) 6 (0.1%)

142 (2.3 %)39 (0.6%)

0 (0%)

P<0.0001P=0.0071P=0.015

Workload

Sampling interval Mean (std) 2.5 (0.5) h 2.2 (0.4) h P<0.0001

Clinical validation of LOGIC-Insulin

1. Randomized Controlled Trial 1 (single-centre)

• 300 patients

• More efficient and safer glucose control than Leuven

nurses

• Van Herpe et al. Diabetes Care 2013

2. Randomized Controlled Trial 2 (multi-centre)

• 1550 patients

� UZ Leuven

� Jessa Hasselt

� AMC Amsterdam

• Ongoing

1. Randomized Controlled Trial 1 (single-centre)

• 300 patients

• More efficient and safer glucose control than Leuven

nurses

• Van Herpe et al. Diabetes Care 2013

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First impressions RCT 2

• Design of new CE-proof graphical user interface� Stable, clear and easy-to-use

� Risk management analysis

� Test procedures

• Easy and remote installation� Server-based

� Cloud-based

• Easy implementation� > 500 nurses trained

� Nurses’ satisfaction high

• Flexible blood glucose targets� UZ Leuven – target blood glucose 80-110 mg/dL

� Jessa Hasselt – target blood glucose 80-110 mg/dL

� AMC Amsterdam – target blood glucose 90-145 mg/dL

• Feb 24, 2014 – ongoing� No safety issues

� No stability issues

• Results: � Q1 2015

• Tight blood glucose control saves lives and reduces costs…

…but difficult implementation in clinical practice

Conclusion

• Therefore, we developed LOGIC-Insulin: – Medical software that assists the ICU nurse in this complex

process

– Strong clinical validation

– RCT 1:• 300 critically ill patients

• More efficient and safer glucose control than ‘gold standard’ nurses

– RCT 2:• 1550 critically ill patients

• Ongoing

• Ongoing process of CE-marking this medical device

• LOGIC-Insulin will be available soon!

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• ICU - Nursing staff

• Team LOGIC-Insulin• Dieter Mesotten, MD, PhD

• Guy Veraghtert, MSc

• Pieter Wouters, MSc

• Jan Vermeyen, RN

• Sylvia Van Hulle, RN

• Alexandra Hendrickx, RN

• Jeroen Herbots, MD

• Evy Voets, MD

• Jo Buyens, MD

• Bart De Moor, PhD

• Greet Van den Berghe, MD, PhD

Acknowledgements

Thank you