D3 Blood Glucose Control in Critically Ill Patients:  Rationale and Measurement for Improvement - P. Dodek
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D3 Blood Glucose Control in Critically Ill Patients: Rationale and Measurement for Improvement - P. Dodek

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D3 Blood Glucose Control in Critically Ill Patients: Rationale and Measurement for Improvement - P. Dodek Presentation Transcript

  • 1. Glycemic Control in Critical Care Rationale for Critically Ill Patients and Measurement for Quality Improvement Peter Dodek, MD MHSc
  • 2. 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
  • 3. Hyperglycemia – traditional view• “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”
  • 4. Hyperglycemia in Critical Illness Bochicchio et al. Adv Surg 2008
  • 5. 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
  • 6. 34% relative reduction in risk of in-hospital death
  • 7. Risk of death not significantly different at any time point
  • 8. In critically ill adultpatients, tight glucosecontrol is not associatedwith significantly reducedhospital mortality but isassociated with anincreased risk ofhypoglycemia.JAMA. 2008;300(8):933-944
  • 9. The NICE-SUGAR Study
  • 10. 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
  • 11. NICE-SUGAR: Average (95%CI) time- weighted blood glucose 10 9 Conventional Therapy Blood Glucose Level 8 7 Intensive Therapy 6 5 4 Baseline 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Day after Randomisation Conventional 2995 2233 1380 909 583 Intensive 2989 2260 1428 908 562© The NICE SUGAR StudyInvestigators 2009 NICE-SUGAR investigators NEJM 2009
  • 12. NICE-SUGAR: Mortality Outcomes Intensive Conventional Odds ratio Glucose Glucose Control Control (95% CI)Dead at 28 670/3010 627/3012 1.09 p = 0.17 days 22.3% 20.8% (0.96 - 1.23)Dead at 90 829/3010 751/3012 1.14 p = 0.02 days 27.5% 24.9% (1.02 - 1.28) Adjusted for operative Adjusted admission, geographic 1.14mortality at region, age, admission p = 0.04 90 days source, APACHE II score, (1.01 - 1.29) mechanical ventilation© The NICE SUGAR Study NICE-SUGAR investigators NEJM 2009Investigators 2009
  • 13. NICE-SUGAR: Survival© The NICE SUGAR Study NICE-SUGAR investigators NEJM 2009Investigators 2009
  • 14. NICE-SUGAR: Severe hypoglycemia (≤2.2mmol/L: ≤40mg/dL) Intensive Conventional Odds ratio Glucose Glucose Control Control (95% CI) 206/3016 15/3014 14.7 Patients p <0.001 6.8% 0.5% (9.0 – 25.9)Episodes per 272/3016 16/3014 p <0.001100 patients 9.0 per 100 0.5 per 100Hypoglycemia associated with all deaths, and deaths due to cardiovascular or infectious diseases© The NICE SUGAR StudyInvestigators 2009 •NICE-SUGAR investigators NEJM 2009
  • 15. The Meaning of Glucose Control1. Accurate measures of glucose concentration2. Sensible and feasible approach to titration of insulin in patients who are hyperglycemic Insulin protocol/algorithm3. Summary measures over time
  • 16. Measures of Glucose Control1. Central Tendency – Average, time-average glucose (area under curve), hyperglycemic index (area under curve above a threshold), median glucose2. 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
  • 17. Hyperglycemic Index Vogelzang M et al. Crit Care 8: R122-R127, 2004.
  • 18. Glycemic Penalty Index Van Herpe et al Crit Care 2004Each value of glucose outside the desired range is given penalty point(s)
  • 19. Glucose Variability—1 Hermanides et al. Crit Care Med. 2010
  • 20. Glucose Variability—2 Hermanides et al. Crit Care Med. 2010
  • 21. 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
  • 22. Example 1: All observations included: Method I Method II (%) Method III (%) (Area under curve above (Total hours when Glucose > (Total number of observations when threshold/ hours 10/ hours observed) Glucose>10/ observed) Total number of observations) 1.41 45.4% 52.9% (9/17)
  • 23. Example 1 : Removing a few observations Method I Method II (%) Method III (%) (Area under curve above (Total hours when Glucose > (Total number of observations when threshold/ hours 10/ Glucose>10/ observed) Total hours observed) Total number of observations) 1.35 43.5% 42.8% (6/14)
  • 24. Example 2 : All observations includedMethod I Method II (%) Method III (%)(Area under curve above (Total hours when Glucose > (Total number of observations whenthreshold/ hours observed) 10/ Glucose>10/ Total hours observed) Total number of observations)0.78 37.6% 32.3% (11/34)
  • 25. Example 2 : Removing a few observationsMethod I Method II (%) Method III (%)(Area under curve above (Total hours when Glucose > (Total number of observations whenthreshold/ hours observed) 10/ Glucose>10/ Total hours observed) Total number of observations)0.79 37.6% 25.8% (8/31)
  • 26. 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
  • 27. 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)
  • 28. 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.