d3 blood glucose control in critically ill patients: rationale and measurement for improvement - p....

Glycemic Control in Critical Care

Rationale for Critically Ill Patients andMeasurement for Quality

ImprovementPeter Dodek, MD MHSc

Outline

• Hyperglycemia and the need for glucose control

• Trials of glucose control in the ICU• The meaning of glucose control• Measures of glucose control• Advice about point of care testing• Suggestions for action

• “Normal” in critically ill patients. • Acceptable component of the normal stress

response• Short term moderate hyperglycaemia

harmless• Hypoglycaemia is dangerous• “commence insulin if blood glucose

>12mmol/L, maintain in range 6 - 10mmol/L”

Hyperglycemia – traditional view

Hyperglycemia in Critical Illness

Bochicchio et al. Adv Surg 2008

Rationale for Glucose Control

• Hyperglycemia impairs neutrophil function and is associated with increased risk of death, with or without underlying diabetes mellitus

• Hypoglycemia is associated with increased risk of death

• Variability in glucose concentration is also associated with increased risk of death

34% relative reduction in risk of in-hospital death

Risk of death not significantly different at any time point

In critically ill adult patients, tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk of hypoglycemia.

JAMA. 2008;300(8):933-944

The NICE-SUGAR Study

NICE – SUGAR Study

• Hypothesis– there is no difference in the relative risk of death

(at 90 days) between ICU patients assigned a glucose range of 4.5 - 6.0 mmol/L and those assigned a glucose range of 10.0 mmol/L or less

© The NICE SUGAR Study Investigators 2009

NICE-SUGAR: Average (95%CI) time-weighted blood glucose

45

67

89

10

Day after Randomisation

Blo

od

Glu

cose

Le

vel

Conventional Therapy

Intensive Therapy

Baseline 1 2 3 4 5 6 7 8 9 10 11 12 13 14

2995 2233 1380 909 5832989 2260 1428 908 562

ConventionalIntensive

NICE-SUGAR investigators NEJM 2009


NICE-SUGAR: Mortality Outcomes

Intensive Glucose Control

Conventional Glucose Control

Odds ratio

(95% CI)

Dead at 28 days

670/3010

22.3%

627/3012

20.8%

1.09

(0.96 - 1.23)p = 0.17

Dead at 90 days

829/3010

27.5%

751/3012

24.9%

1.14

(1.02 - 1.28)p = 0.02

Adjusted mortality at

90 days

Adjusted for operative admission, geographic region, age, admission

source, APACHE II score, mechanical ventilation

1.14

(1.01 - 1.29)p = 0.04



NICE-SUGAR: Survival



NICE-SUGAR: Severe hypoglycemia(≤2.2mmol/L: ≤40mg/dL)

Intensive Glucose Control

Conventional Glucose Control

Odds ratio

(95% CI)

Patients206/3016

6.8%

15/3014

0.5%

14.7

(9.0 – 25.9)p <0.001

Episodes per 100 patients

272/3016

9.0 per 100

16/3014

0.5 per 100p <0.001

Hypoglycemia associated with all deaths, and deaths due to cardiovascular or infectious diseases

•NICE-SUGAR investigators NEJM 2009

The Meaning of Glucose Control

1. Accurate measures of glucose concentration

2. Sensible and feasible approach to titration of insulin in patients who are hyperglycemic

Insulin protocol/algorithm

3. Summary measures over time

Measures of Glucose Control

1. Central Tendency– Average, time-average glucose (area under curve),

hyperglycemic index (area under curve above a threshold), median glucose

2. Variability (Dispersion)– Mean amplitude of glucose excursion, standard

deviation, coefficient of variation, range, maximum glucose, glucose lability index, absolute rate of change, cumulative sum of hyperglycemic indices, glycemic penalty index

Hyperglycemic Index

Vogelzang M et al. Crit Care 8: R122-R127, 2004.

Glycemic Penalty Index

Each value of glucose outside the desired range is given penalty point(s)

Van Herpe et al Crit Care 2004

Glucose Variability—1

Hermanides et al. Crit Care Med. 2010

Glucose Variability—2

Hermanides et al. Crit Care Med. 2010

Why have we chosen the hyperglycemic index?

• A measure of central tendency that incorporates time

• In one study, highest area under receiver operating characteristic curve for 30-day mortality (optimal sensitivity and specificity)

• The only significant glucose index in a multivariate model for 30-day mortality

Method I (Area under curve above threshold/ hours observed)

Method II (%)(Total hours when Glucose > 10/ hours observed)

Method III (%) (Total number of observations when Glucose>10/Total number of observations)

1.41 45.4% 52.9% (9/17)

Example 1: All observations included:

Example 1 : Removing a few observations


Method II (%)(Total hours when Glucose > 10/Total hours observed)


1.35 43.5% 42.8% (6/14)

Example 2 : All observations included




0.78 37.6% 32.3% (11/34)

Example 2 : Removing a few observations




0.79 37.6% 25.8% (8/31)

Advice about point of care testing…

• Use arterial blood• Ensure that the device corrects for [Hb] and is

accurate over a wide range of PaO2

Suggestions:

• Collect glucose concentration and time data for all patients on insulin infusions

• Use hyperglycemic index (or hyperglycemic time index) as measure of control

• Can also calculate hypoglycemic index (area under curve below a threshold) and glucose variability (mean of absolute rate of change)

References

• Vogelzang M et al. Crit Care 2004; 8: R122-R127.• Eslami S et al. Crit Care 2008; 12: R139-R149.• Van Herpe T et al. Crit Care 2008; 12: R24-R37.• Slater-Maclean L et al. Diabetes Tech Ther. 2008; 10: 169-177.• Krinsley JS. Crit Care Med 2008; 36: 3008-3013.• Bochicchio GV et al. Adv Surg 2008; 42: 261-275.• Meynaar IA et al. Crit Care Med 2009; 37: 2691-2696.• Hermanides J et al. Crit Care Med 2010; 38: 838-842.• Mackenzie IMJ et al. Int Care Med 2011; 37: 435-443.• Egi M et al. Chest 2011; 140: 212-220.

d3 blood glucose control in critically ill patients: rationale and measurement for improvement - p....

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