Glycemic Control in Acutely Ill Patients

1. Glycemic Control in Acutely Ill Patients Martin J. Abrahamson, MD FACP Associate Professor of Medicine, Harvard Medical School Senior Vice President for Medical Affairs, Joslin Diabetes Center

2. Questions to Ask • Is hyperglycemia associated with increased morbidity/mortality in acutely ill patients? • Will lowering glucose improve outcomes for acutely ill patients? • What glucose levels should be attained in the acutely ill patient? • How do we best do this?

3. Mortality Increases with Increases in Average ICU BG (1826 consecutive ICU patients 10/99 thru 4/02) Krinsley JS: Mayo Clin Proc. 2003;78:1471-1478.

4. Intensive Insulin Therapy and Mortality in Patients Admitted to SICU • 1548 consecutive admissions to SICU • Randomly assigned (with stratification based on type of critical illness) to conventional vs intensive insulin treatment Van de Berghe G, et al. NEJM 2001;345:1359-1367

5. Intensive Insulin Therapy and Mortality in Patients Admitted to SICU • Conventional treatment • Standardized nutritional therapy and intravenous insulin therapy if BG >215 mg/dl to maintain blood glucose <200 mg/dl. • Intensive therapy • Standardized nutritional therapy and intravenous insulin therapy if BG>110 mg/dl to maintain glucose 80 - 110 mg/dl.

6. Intensive Insulin Therapy in Critically Ill Surgical Patients Van den Berghe et al. NEJM 2001; 345:1359-1367 Glucose in mg/dL

7. Intensive Insulin Therapy in Surgical ICU Patients Reduces Mortality 100 Intensive treatment 96 4.6% mortality 92 8% mortality Survival in ICU (%) Conventional treatment 88 84 80 0 0 20 40 60 80 100 120 140 160 Days after Admission Conventional: insulin when blood glucose > 215 mg/dL mean BG = 153 mg/dL Intensive: insulin when glucose > 110 mg/dL and maintained at 80-110 mg/dL mean BG = 103 mg/dL Van den Berghe, G. NEJM. 2001;345:1359–1367.

8. Intensive Insulin Therapy in Surgical ICU Patients Reduces Morbidity and Mortality Mortality Sepsis Dialysis Blood Transfusion Polyneuropathy Percent Reduction 34% 41% 44% 46% 50% Van den Berghe, G. NEJM. 2001;345:1359–1367.

9. What about Intensive Therapy in the MICU? • 1,200 patients who “were considered to need intensive care for at least 3 days” • Randomized to two groups: • IV insulin to achieve glucose 80-110 mg/dl • Conventional therapy using insulin for blood glucose > 215 mg/dl and tapered when < 180 mg/dl • 16.9% of these patients had diabetes NEJM 354:449, 2006

10. Intensive Insulin Therapy in Critically Ill Medical Patients Van den Berghe et al. NEJM 2006; 354:449-460 Glucose in mg/dL

11. A. Intention-to-Treat Group (n = 1,200) 100 80 Intensive treatment 60 Conventional treatment In-Hospital Survival (%) 100 40 80 60 20 40 First 30 days 0 0 10 20 30 0 0 100 200 300 400 500 Days Intensive Insulin in the MICU Does Not Decrease Mortality • In-hospital deaths • Conventional Therapy: 40% • Intensive Insulin Therapy: 37.3% P = 0.33 NEJM 354:449, 2006

12. B. Subgroup in ICU ≥3 Days (n = 767) 100 80 Intensive treatment 60 In-Hospital Survival (%) 100 Conventional treatment 40 80 60 20 40 First 30 days 0 0 10 20 30 0 0 50 100 150 200 250 300 350 500 Days Subgroup in ICU ≥ 3 days (n = 767) • In-hospital deaths • Conventional Therapy: 52.5% • Intensive Insulin Therapy: 43.0% P = 0.009 NEJM 354:449, 2006

13. A Weaning from Mechanical Ventilation Discharge from ICU Discharge from Hospital 4.0 4.5 5.0 P=0.03 P=0.04 P=0.05 4.0 3.5 4.0 Intensive treatment 3.5 3.0 3.0 2.5 3.0 Cumulative Hazard 2.5 2.0 2.0 2.0 1.5 1.5 Conventional treatment 1.0 1.0 1.0 0.5 0.5 0.0 0.0 0.0 80 80 500 0 10 20 30 40 50 60 70 90 0 20 40 60 100 0 010 200 300 400 600 Days After Admission to ICU > 3 days in ICU (n = 767) B Weaning from Mechanical Ventilation Discharge from ICU Discharge from Hospital 4.0 3.5 P<0.001 5.0 P=0.01 P=0.04 3.5 3.0 Intensive treatment 4.0 3.0 2.5 2.5 3.0 2.0 Cumulative Hazard 2.0 1.5 2.0 1.5 1.0 Conventional treatment 1.0 1.0 0.5 0.5 0.0 0.0 0.0 80 0 20 40 60 100 0 10 20 30 40 50 60 70 80 90 500 0 100 200 300 400 600 Days After Admission to ICU Effect of Intensive Insulin Therapy on Morbidity NEJM 354:449, 2006

14. Conclusions • Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the MICU. • Although the risk of subsequent death and disease was reduced in patients treated for ≥3 days, these patients could not be identified before therapy. NEJM 354:449, 2006

15. Diabetes Care in the Hospital: NICE-SUGAR Study (1) • Largest randomized controlled trial to date • Tested effect of tight glycemic control (target 81–108 mg/dL) on outcomes among 6,104 critically ill participants • Majority (>95%) required mechanical ventilation ADA. IX. Diabetes Care in Specific Settings. Diabetes Care. 2013;36(suppl 1):S46.

16. Diabetes Care in the Hospital: NICE-SUGAR Study (2) • In both surgical/medical patients, 90-day mortality significantly higher in intensively treated vs conventional group (target 144–180 mg/dL) • Severe hypoglycemia more common(6.8% vs 0.5%; P<0.001) • Findings strongly suggest may not be necessary to target blood glucose levels<140 mg/dL; highly stringent target of<110 mg/dL may be dangerous ADA. IX. Diabetes Care in Specific Settings. Diabetes Care. 2013;36(suppl 1):S46.

17. So what glycemic target should be attempted for acutely ill patients admitted with diabetes?

18. ADA Recommendations • Critically ill patients: • 140 – 180 mg/dL • Start iv insulin when glucose exceeds 180 mg/dL • Goal of 110 – 140 mg/dL may be appropriate for some patients if there is no risk of hypoglycemia • Non-critically ill • Premeal < 140 mg/dL mg/dL • Random <180 mg/dL

19. So how do we manage someone who requires insulin and is NPO or too ill to eat?

20. Using Sliding Scale SC Insulin is Like Being on a Roller Coaster! IT IS A RELIC FROM THE PAST AND SHOULD BE AVOIDED WHEREVER AND WHENEVER POSSIBLE!!

21. Estimating Insulin Dose for Infusion • Infusion of 1.0 - 2.0 units/hrusually maintains blood glucose in 120 - 180mg/dL range • Insulin requirements depend on • Previous therapy • Degree of control • Use of steroids • Presence of sepsis • Type of surgery • Increased insulin requirements for renal transplant and open heart surgery

22. Guidelines for Insulin Infusion • Decreased insulin needs • Patients requiring diet and/or oral agents • Patients taking less than 50 U of insulin per day • Increased insulin needs • Obesity, hepatic disease (x 1.5) • Steroid therapy (x2) • Sepsis (x2) • Renal transplant (x 2) • Open heart surgery (x 3-5)

23. Insulin Infusion Algorithm • Decision to initiate iv insulin • If BG < 200 mg/dL start with D5 ½ N Saline at 60 – 100 cc/hr • If BG > 300 mg/dL give iv regular insulin 0.1U/kg stat • Initiate at an hourly rate of total daily dose of insulin / 24 • For patients not usually on insulin start at 0.02 U/kg/hr • Check BG hourly

24. Adjustment of Insulin is dependent on current glucose, previous glucose and rate of change of glucose

25. Transitioning to SC Insulin • Do not stop iv insulin before giving some short acting insulin sc • Usually continue iv infusion by about 1 hour after administration of short acting sc insulin • Plan to stop iv after a meal – preferably during the day • Ensure that there is always intermediate or long acting insulin given to cover basal requirements

26. Remember – Insulin Requirements.. • Basal • Prandial/Nutritional • Correction or Supplemental

27. Summary • Hyperglycemia is associated with increased morbidity and mortality in acutely ill patients • Maintaining glucose levels between 140 and 180 mg/dL in acutely ill patients is associated with the least morbidity and optimal outcomes • Using iv insulin infusion to achieve this in the ICU is the preferred modality of administering insulin