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Improving Glycemic Control in the Hospital

Improving Glycemic Control in the Hospital. Anthony DeSantis, MD Clinical Asst. Professor Division of Metabolism, Endocrinology and Nutrition University of Washington Medical School. Three Types of Hyperglycemic Patient. Known history of diabetes Existing, but unrecognized, diabetes

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Improving Glycemic Control in the Hospital

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  1. Improving Glycemic Control in the Hospital Anthony DeSantis, MD Clinical Asst. Professor Division of Metabolism, Endocrinology and Nutrition University of Washington Medical School

  2. Three Types of Hyperglycemic Patient • Known history of diabetes • Existing, but unrecognized, diabetes • Stress hyperglycemia Clement et al. Diabetes Care. 2004;27:553-591.

  3. Hyperglycemia Adversely Affects Outcomes • Hyperglycemia impacts • Mortality • Morbidity • Rate of infections • Length of stay (LOS)

  4. 38% of Hospital Admissions Exhibit Hyperglycemia 2030 consecutive adult patients admitted between July and October 1998 38% had hyperglycemia* *Hyperglycemia defined as admission or FPG ≥126 mg/dL or random BG ≥200 mg/dL Umpierrez et al. J Clin Endocrinol Metab. 2002;87:978-982.

  5. New-onset Hyperglycemia: Highest Mortality Rates Total Inpatient Mortality ICU Mortality 31%† *P<0.01 n=1886 †P<0.01 n=243 16%* 11% 10% 3% 1.7% Umpierrez et al. J Clin Endocrinol Metab. 2002;87:978-982.

  6. Hyperglycemia Impacts Rate of Infections Note inflection point Rates of deep sternal wound infection in 4864 patients with diabetes who underwent an open-heart surgical procedure P=0.001 Rate of infection, % 3-day average postoperative blood glucose, mg/dL Furnary et al. Endocr Pract. 2004;10(suppl 2):21-33.

  7. HYPERGLYCEMIAIndex of disease severity 14.5% Mortality % 6.0% 4.1% 2.3% 0.9% 1.3% Average post-op glucose Furnary et al J Thorac Cardiovasc Surg 2003;125:1007-21

  8. Hyperglycemia and Mortality Inpatient hyperglycemia clearly associated with increased morbidity and mortality Can interventions, which reduce inpatient hyperglycemia acutely, decrease this increased morbidity and mortality?

  9. Intensive Insulin Therapy in Critically Ill Surgical Patients Improves Survival 100 Intensive treatment 96 92 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. Intensive: insulin when glucose > 110 mg/dL and maintained at 80–110 mg/dL. 9 van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.

  10. Intensive Insulin Therapy in Critically Ill Surgical Patients: Morbidity and Mortality Benefits Intensive therapy to achieve blood glucose levels of 80–110 mg/dL reduced mortality (-34%), sepsis (-46%), dialysis (-41%), blood transfusion (-50%), and polyneuropathy (-44%) Mortality Sepsis Dialysis Blood Transfusion Polyneuropathy N = 1,548 Reduction(%) 34% 41% 44% 46% 50% 10 van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.

  11. The Belgian StudyPost-Hoc Analysis of Various Outcomes by Glucose Levels Achieved in Patients Staying in ICU > 5 Days 11 van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367

  12. Portland Diabetes Project: Mortality 10 CII 8 Patients with diabetes 6 Mortality(%) Patients without 4 diabetes 2 0 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 Year Reprinted from Furnary AP, et al. J Thorac Cardiovasc Surg. 2003;125:1007–1021 with permission from American Association for Thoracic Surgery.

  13. Inpatient Glycemic Goals  American Diabetes Association. Diabetes Care. 2006;29:S4-S42. Garber et al. Endocr Pract. 2004;10:77-82.

  14. Recent Studies Suggest that Perhaps these Targets Are Too Strict Frequency of Hypoglycemia (<40mg/dl) 1van den Berghe G, et al. N Engl J Med. 2001;345:1359 4Preiser &Devos, Crit Care Med 2007;35:S503-S507 2van den Berghe G et al. N Engl J Med 2006;354:449 5NICE-SUGAR Invest, N Engl J Med 2009;360:1283 3Brunkhorst et al., N Engl J Med 2008;358:125-139

  15. The Belgian MICU TrialImpact of Intensive Insulin * Van den Berghe N Engl J Med 2006;354:449-61 * p= 0.009

  16. The Belgian MICU TrialImpact of Intensive Insulin Van den Berghe N Engl J Med 2006;354:449-61

  17. VISEP Trial Overall Survival Blood Glucose 100 Conventional therapy (n=290) 80 200 60 150 Probability of Survival (%) Intensive therapy (n=247) Mean Blood Glucose (mg/dL) 40 100 Conventional therapy 50 20 Intensive therapy 0 0 10 20 30 40 50 60 70 80 90 100 0 0 1 2 9 10 11 12 13 14 3 4 5 6 7 8 Days Days Data from 537 patients: 247 received IIT goal: 80 – 110 mg/dL: mean BG 112 mg/dL 290 received CIT goal: 180 – 200 mg/dL: mean BG 151 mg/dL IIT, intensive insulin therapy; CIT, conventional insulin therapy. Brunkhorst FM et al. N Engl J Med. 2008;358:125-139.

  18. VISEP Trial *SOFA – sequental organ failure assessment Brunkhorst FM et al. N Engl J Med. 2008;358:125-139.

  19. The NICE-SUGAR Study IIT goal: 81 – 108 mg/dL (mean BG 118 mg/dL) CIT goal: <180 mg/dL (mean BG 145 mg/dL) Nice Sugar, NEJM 2009;360:1283

  20. The NICE-SUGAR Study Nice Sugar, NEJM 2009;360:1283 90 day mortality: IIT: 829 patients (27.5%), CIT: 751 (24.9%) Absolute mortality difference: 2.6% (95% CI, 0.4 to 4.8); Odds ratio for death with IIT was 1.14 (95% CI, 1.02 to 1.28; P = 0.02).

  21. Probability of Survival and Odds Ratios for Death, According to Treatment Group Operative Admission Diabetes Severe Sepsis Trauma Apache Score Corticosteroids All deaths at day 90 Favors Favors IIT Conventional Nice Sugar, NEJM 2009;360:1283

  22. Is Hypoglycemia Life-threatening?

  23. Hypoglycemic events Favors IIT Favors Control Griesdale et al., CMAJ 2009;180:821

  24. Favors IIT Favors Control All Mixed ICU 0.99 (0.87-1.12) All Medical ICU 1.00 (0.78-1.28) All Surgical ICU 0.63 (0.44-0.91) ALL ICU 0.93 (0.83-1.04)

  25. Mean Glucose & In-Hospital Mortality in 16,871 Patients with AMI Reference: Mean BG 100-110 mg/dl Kosiborod M et al. Circulation 2008:117:1018

  26. Relationship between Spontaneous and Iatrogenic Hypoglycemia and Mortality in Patients Hospitalized with Acute MI Retrospective analysis of 7820 patients hospitalized with acute MI in 40 hospitals in US 1/01 – 12/05, with glucose levels > 140 mg/dl on admission 4775 never received insulin 3045 received insulin Kosiborod et al., JAMA 2009;301:1556

  27. Hypoglycemia* in Acute MI *Glucose < 60 m/dL Kosiborod et al., JAMA 2009;301:1556

  28. Multivariable Analysis Hypoglycemia in ACS Kosiborod et al., JAMA 2009;301:1556

  29. Is Hypoglycemia Life-threatening? • Hypoglycemia (BG < 40 mg/dl) has been reported in 5 - 28% of patients on CII • Inpatient hypoglycemia is associated with poor clinical outcome • No direct evidence indicating insulin-induced hypoglycemia results in increased mortality • Similar to hyperglycemia, severe hypoglycemia appears to be a marker of poor ICU outcome

  30. GLYCEMIC TARGETS

  31. ADA/AACE Target Glucose Levels in ICU Patients ICU setting: Insulin infusion should be used to control hyperglycemia Starting threshold of no higher than 180 mg/dl Once IV insulin is started, the glucose level should be maintained between 140 and 180 mg/dl Lower glucose targets (110-140 mg/dl) may be appropriate in selected patients   Targets <110 mg/dL are not recommended Not recommended < 110 Acceptable 110-140 Recommended 140-180 Not recommended >180 ADA/AACE Inpatient Task Force Endocrine Practice 2009;15;1-17

  32. ADA/AACE Target Glucose Levels in non-ICU Patients Non-ICU setting: Pre-meal glucose targets <140 mg/dL Random BG <180 mg/dL To avoid hypoglycemia, reassess insulin regimen if BG levels fall below 100 mg/dL Occasional patients may be maintained with a glucose range below or above these cut-points Hypoglycemia= BG < 70 mg/dl Severe hypoglycemia= BG < 40 mg/dl ADA/AACE Inpatient Task Force Endocrine Practice 2009;15:1-17

  33. Achieving Tight Glycemic Targets “Insulin, given either intravenously as a continuous infusion or subcutaneously, is currently the only available agent for effectively controlling glycemia in the hospital.” Insulin is SEXY Again Abe DeSantis, MD ACE Position Statement on Inpatient Diabetes and Metabolic Control, 2004.

  34. Performance Improvement/ QI staff P&T Committee Critical Care physicians Other internists Patient Safety Committee Lab Multidisciplinary Team Extends Beyond Caregivers Chief residents/ residency program directors Departmental committees Biomedical, medical records, CPOE expertise Unit clerks/ secretaries Surgery, Trauma, Orthopedics, Anesthesiology leaders Endocrin-ologists GLYCEMIC CONTROL COMMITTEE Patient Representa- tives Hospitalists • Pharmacists OR or Perioperative Committees Forms Committee • Nursing groups Hospital Informatics Nutritionists/ Dietitians Maynard et al. SHM Glycemic Control Workgroup. Available at: :http://www.hospitalmedicine.org/AM/Template.cfm?Section=Quality_Improvement_Resource_Rooms1&Template=/CM/HTMLDisplay.cfm&ContentID=4337.

  35. Incidence Inpatient HyperglycemiaNMH • Documented serum/capillary blood glucose values NMH admits 9/03 - 10/03. • 26% of admissions with blood glucose value > 200 mg/dl. • Mean BG among those medically treated for DM • 213 mg/dl

  36. Post-operative Check CBG every 4hrs x 48 hours BG <110 mg/dl BG >110 mg/dl BG >200 mg/dl After initial 48 hours, serum fasting glucose qAM Repeat CBG 30 minutes from previous BG <110 mg/dl BG >110 mg/dl Start IV insulin protocol Plans for dietary advance Continue while NPO/Critically ill Consult GMS Monitor glucose; titrate insulin D/C IV insulin; convert to SQ DeSantis, et al Endocr Practice 2006;12:491-505 Consider Nutrition consult Consider Diabetes educator consult

  37. IV Insulin Therapy

  38. IV Insulin Therapy: Recommended Uses • Best method to achieve quick glycemic control • IV insulin recommended over SC administration for • Hyperglycemic emergencies • Critical care illness • MI or cardiogenic shock • Care following cardiac surgical procedures • Type 1 DM NPO • Corticosteroid Therapy SC = subcutaneous; MI = myocardial infarction. Bode et al. Endocr Pract. 2004;10(suppl 2):71-80.

  39. The Ideal IV Insulin Protocol • Easily ordered (signature only) • Effective (gets to goal safely) • Maintains BG within a defined target range • Includes an algorithm for making temporary corrective increments or decrements of insulin infusion rate • Safe (minimal risk of hypoglycemia) • Includes nutritional and electrolyte support • Easily implemented • Can be executed by nursing staff in response to a single physician order Moghissi. Cleve Clin J Med. 2004;71:801-808.

  40. Hyperglycemia ManagementInitiation of Insulin Drip Therapy • 32 yo with Type 1 DM, s/p appendectomy. • NPO • BS= 278. • BG q 1 hour DeSantis, et al Endocr Practice 2006;12:491-505

  41. Hyperglycemia ManagementTitration of Insulin Drip Therapy • Adjust insulin drip based on current BG and rate of BG change • One hour later, BG=310. Previous BG 278. • An increase of 32. DeSantis, et al Endocr Practice 2006;12:491-505

  42. Hyperglycemia ManagementTitration of Insulin Drip Therapy • One hour later, BG= 220 • Previous BG=310, a decrease of 90 DeSantis, et al Endocr Practice 2006;12:491-505

  43. Critical Care Improvement Project – Glucose Control Reduce mortality rate by 20% in the ICUs through the implementation of tight glycemic control. UCL Spread LCL The decrease in the critical care mortality rate is statistical significant. The Chi Squared Test P-value = 0.03 (Prior 12 months compared to Feb’05 – Apr’05) • Baseline Avg Blood glucose 144.3 +/-39 mg/dl • May-05 Avg Blood glucose 112.8 +/- 54 mg/dl

  44. Points to Consider When Transitioning From IV to SC Insulin • What are patients eating? When? • Continue IV insulin until patient is able to tolerate solid-food intake • Continue IV insulin at least 2 hours after first SC injection to cover “gaps” (longer if first injection is basal; consider adding rapid-acting insulin for “gap coverage”) • What are the concomitant therapies? • Oral insulin secretagogues will lower BG faster than other agents, increasing risk of hypoglycemia • Will resolution of the illness alleviate insulin needs? • Decrease in TDD of 20%–33% not uncommon

  45. Subcutaneous InsulinMaintaining Physiologic Insulin Delivery in the Hospital BE THE PANCREAS!

  46. Dark Side  The of Diabetes Management The Sliding Scale • Dose in reaction to a single retrospective blood glucose measurement • Does not provide basal insulin coverage • Provides supplemental insulin after hyperglycemia occurs • Does not consider nutritional changes or diurnal insulin requirements • Nonphysiologic dosing places patients at risk of large fluctuations in blood glucose levels • Increased incidence of hyperglycemic and hypoglycemic episodes1 1. Queale et al. Arch Intern Med. 1997;157:545-552.

  47. RABBIT 2 Trial • Prospective randomized trial of 130 insulin naïve T2DM non-ICU inpatients • Admission blood glucose b/w 140-400 mg/dl • Basal- bolus insulin with glargine and glulisine vs Regular insulin SS

  48. RABBIT 2 Trial Mean Blood glucose mg/dl DAYS Umpierrez, et al Diabetes Care 30;2181-86,2007

  49. RABBIT 2 TRIALn=9 SSI Failures Mean Blood glucose mg/dl DAYS

  50. NPH Detemir (Levemir)  Which insulins are best for basal coverage? Glargine (Lantus) Regular Lispro (Humalog) Aspart (Novolog) Glulisine (Apidra) Insulin Effect Inhaled insulin 0 6 12 18 24 Time (hours)

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