2. Hyperglycemia Management in the Hospital Tools to Make the Journey Safer & More Comfortable Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Member of the SIG of GHA for Diabetes

3. Objectives l Understand the need for protocols for managing hyperglycemia and diabetes in the hospital l Present what the Georgia Hospital Association (GHA) has done to date and what tools we are using to accomplish this task

4. GHA Special Interest Group for Diabetes l Formed in 2003 with the mission to monitor, evaluate and enhance diabetes care in the state of Georgia l Team composed of over 50 medical specialists with interest in diabetes care in the hospital l Team members are MDs, RNs, RDs, PharmDs, Administrators, Insurance Reps, etc

6. Key Elements of Inpatient Orders l Conforms with the current guidelines (AACE) l Simple and user friendly l Identifies patients needing initiation or modification of insulin therapy l Addresses the administration requirements for insulin infusion and the unique nutritional requirements l Addresses consultation/educational needs for patients

7. The Increasing Rate of Diabetes Among Hospitalized Patients 48% Available at: http://www.cdc.gov/diabetes/statistics/dmany/fig1.htm. Accessed June 15, 2004.

8. Hyperglycemia in Hospitalized Patients l Hyperglycemia (>200 mg/dL x 2) occurred in 38% of hospitalized patients –26% had known history of diabetes –12% had no history of diabetes l Newly discovered hyperglycemia was associated with: –Longer hospital stays – higher admission rates to intensive care units –Less chance to be discharged to home (required more transitional or nursing home care) Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978–982.

9. Hyperglycemia Is an Independent Marker of Inpatient Mortality in Patients With Undiagnosed Diabetes Adapted from Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978–982. In-hospital Mortality Rate (%) Newly Discovered Hyperglycemia Patients With History of Diabetes Patients With Normoglycemia P < 0.01

10. Prevalence of Hyperglycemia in 181 Cardiac Patients Without Known Diabetes Norhammar A. Lancet. 2002;359:2140-2144. Percentage of Population (n = 1181) 66% of AMI patients have IGT or previously undiagnosed T2DM on 75 g OGTT (35% IGT; 31% DM) 66% of AMI patients have IGT or previously undiagnosed T2DM on 75 g OGTT (35% IGT; 31% DM)

11. Hyperglycemia in Hospitalized Patients –Surgery –Catheters –Intravenous Access Problems with wound healing Problems with tissue and organ perfusion High-risk for bacterial infection

12. Hospital Costs Account for Majority of Total Costs of Diabetes Hogan P, et al. Diabetes Care. 2003;26:917 – 932. Per Capita Healthcare Expenditures (2002) DiabetesWithout diabetes

13. Benefits of Improved Glucose Control in the Hospital l Aggressive insulin treatment improves –ICU outcomes –Outcomes post-MI –Cardiac surgery outcomes

14. Mortality of DM Patients Undergoing CABG Furnary et al J Thorac Cardiovasc Surg 2003;123:1007-21

15. Costs of Hyperglycemia in the Hospital For each 50 mg/dL rise in glucose: Length of Stay increases by 0.76 days Hospital Charges increase by $2824 Hospital Costs increase by $1769 Furnary et al Am Thorac Surg 2003;75:1392-9

16. Intensive Insulin Therapy in Critically Ill PatientsMorbidity and Mortality Benefits van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367. Percent Reduction MortalitySepsisDialysisPolyneuropathy Blood Transfusion 34% 46% 41% 44% 50%

17. P=0.000 9 P=0.026 BG<110 110<BG<150 BG>150 Surgical ICU Mortality Effect of Average BG Van den Berghe et al (Crit Care Med 2003; 31:359-366)

18. Hyperglycemia and Hospital Mortality 1826 consecutive ICU patients 10/99 thru 4/02, Stamford CT Krinsley JS: Mayo Clin Proc 78: 1471-1478, 2003

19. Intensive Insulin Management in Medical-Surgical ICU (n = 1600) Krinsley SK. Mayo Clin Proc. 2004;79(8):992-1000. Mean BG Levels (mg/dL) P < 0.001 Nursing Requirements (hrs/patient day) P = NS Hospital Mortality (%) P < 0.002 29.3% Reduction

20. Glycemic threshold in ICU Patients l BG < 110 mg/dl Van den Berghe et al Crit Care Med 2003; 31(2):359-66 Finney SJ et al JAMA 2003;290(15):2041-47 Krinsley SK. Mayo Clin Proc. 2004;79(8):992-1000

21. What About Medical Patients?

22. Cardiovascular Risk Mortality After MI Reduced by Insulin Therapy in the DIGAMI Study Malmberg, et al. BMJ. 1997;314:1512-1515. All Subjects (N = 620) Risk reduction (28%) P =.011 Standard treatment 0.3.2.4.7.1.5.6 01 Years of Follow-up 2345 Low-risk and Not Previously on Insulin (N = 272) Risk reduction (51%) P =.0004 IV Insulin 48 hours, then4 injections daily 0.3.2.4.7.1.5.6 01 Years of Follow-up 2345 6-11

23. Other Medical Conditions l Infection data supports BG < 130 mg/dl Hartford ICU study 125 mg/dl vs 179 mg/dl 10X decrease in infections l Stroke data supports BG < 130 mg/dl l Pregnancy data supports BG < 100 mg/dl

24. Target blood glucose in mg/dL l 80 – 110 in ICU patients l 80 – 140 in other Surgical and Medical Patients l 70 – 100 in Pregnancy Bode et al Endocrine Practice July 2004

25. Hospital Targets for Glucose AACE and ADA Guidelines: Dec 2003 80–110 mg/dL ICU <110 mg/dL preprandial and <180 mg/dL post meal in other units Modify if: cardiac disease (unstable) hypoglycemic unawareness recurrent hypoglycemia New

26. Conclusion All hospital patients should have normal glucose

27. Insulin The agent we have to control glucose only most powerful

28. Methods For Managing Hospitalized Persons with Diabetes l Continuous Variable Rate IV Insulin Drip Major Surgery, NPO, Unstable, MI, DKA, Hyperglycemia, Steroids, Gastroparesis, Delivery, etc l Basal / Bolus Therapy (MDI) when eating

29. Threshold blood glucose in mg/dL for starting IV insulin infusion l Peri-operative care:> 140 l ICU care: > 110 - 140 * l Non-surgical illness:> 140 - 180 * * l Pregnancy> 100 * Van den Berghes study supports 110; Finneys study supports 145 * * If drip indication is failure of SQ therapy, use 180 ; if indication is specific condition ( DM 1/ NPO, MI, etc ), use 140

30. The Ideal IV Insulin Protocol l Easily ordered (signature only) l Effective (Gets to goal quickly) l Safe (Minimal risk of hypoglycemia) l Easily implemented l Able to be used hospital wide

31. Essentials of a good IV Insulin Algorithm l Easily implemented by nursing staff l Able to seek BG range via: - Hourly BG monitoring - Adjusts to the insulin sensitivity of the patient

32. Various Protocols Exist l DIGAMI (studied in acute MI setting) l van den Berghe (studied in critical care setting) l Portland Protocol (used in surgical setting) l Markovitz (studied in postoperative heart surgery patients) l Yale Protocol (studied in medical intensive care setting)

33. A System for the Maintenance of Overnight Euglycemia and the Calculation of Basal Insulin Requirements in Insulin-Dependent Diabetics Practical Closed Loop Insulin Delivery 1/slope = Multiplier = 0.02 0 1 2 3 4 5 6 0100200300400 Glucose (mg/dl) Insulin Rate (U/hr) NEIL H. WHITE, M.D., DONALD SKOR, M.D., JULIO V. SANTIAGO, M.D.; Ann Int Med 1982 ;97:210-214

34. Continuous Variable Rate IV Insulin Drip l Mix Drip with 125 units Regular Insulin into 250 cc NS (0.5 U/cc) or 1 U/cc l Starting Rate Units / hour = (BG – 60) x 0.02 where BG is current Blood Glucose and 0.02 is the multiplier l Check glucose every hour and adjust drip l Adjust Multiplier to keep in desired glucose target range (80 to 110 in ICU; 100 to 140 on floor)

35. Continuous Variable Rate IV Insulin Drip l Adjust Multiplier (initially 0.02) to obtain glucose in target range 100 to 140 mg/dL If BG > 140 mg/dL and has not decreased by 15% in the last hour, increase by 0.01 If BG < 100 mg/dL, decrease by 0.01 If BG 100 to 140 mg/dL, no change in Multiplier l If BG is < 80 mg/dL, Give D50 cc = (100 – BG) x 0.4 l Give continuous rate of Glucose in IVFs l Once eating, continue drip till 2 hours post SQ insulin

36. Multiplier Principles Insulin Units / Hour Glucose mg/ dl Davidson et al, Diabetes Care 28(10): 2418-2423, 2005

37. Computerized Insulin Delivery l In 1984, R Dennis Steed computerized our insulin drip orders into Glucommander l Glucommander used extensively since 1985 in our hospitals as well as 40 plus DTCA hospitals l In 1996, Roche and MiniMed purchased the rights to use Glucommander in their combined meter pump system. Multi-center trials done and successful. l Product died when IV insulin had not been FDA approved

38. Glucommander Average and Standard Deviation of of All Runs 1985 to 1998; 5808 runs, 120,618 BGs Davidson et al, Diabetes Care 28(10): 2418-2423, 2005

39. Hours Glucose Multiplier Insulin Glucose Typical Glucommander Run Hi Low Davidson et al, Diabetes Care 28(10): 2418-2423, 2005

40. 1 Center Experience with Glucommander over a 1 year period (2004 to 2005) l East Carolina University – 750 bed hospital with 7 ICUs l Glucommander initiated in all ICU patients with BG >140 mg/dL l 7 FTEs hired to implement the program l Average BG went from 167 to 126 mg/dl l LOS decreased in ICU by 1 day; in Hospital by 0.3 days l No central line infections l Net savings to hospital 2 million dollars (470% Return on Investment) Personal Communication with Chris Newton, MD FACE

41. Current Status Of Glucommander l Being studied in 8 hospitals vs Hirsh et al drip l Discussions are on going with several groups to bring the device to all interested hospitals l Available for research purposes via www.glucommander.com

47. Converting to SC insulin l If More than 0.5 u/hr IV insulin required with normal BG, start long-acting insulin (glargine) Exception: if no prior DM and normal A1C, may not need SC insulin Exception: if no prior DM and normal A1C, may not need SC insulin l Must start SC insulin at least 1 to 2 hours before stopping IV insulin l Some centers start long-acting insulin on initiation of IV insulin or the night before stopping the drip

48. Intravenous Insulin Infusion Under Basal Conditions Correlates Well With Subsequent Subcutaneous Insulin Requirement Hawkins et al. Endocr Pract. 1995;1:385–389. Units IV Units SQ Total Intravenous vs. Subcutaneous 24-hour Insulin Requirements, units 275 250 225 200 175 150 125 100 75 50 25 0 2752502252001751501251007550250

50. The Physiological Insulin Profile Adapted from Polonsky, et al. 1988. 10 20 30 Insulin (mU/l) 0 40 50 60 70 Short-lived, rapidly generated prandial insulin peaks Low, steady, basal insulin profile Normal free insulin levels from genuine data (mean) 060009001200150018002100240003000600 BreakfastLunchDinner

51. 4:0016:0020:0024:004:00 BreakfastLunchDinner 8:00 12:008:00 Time Glargine or Detemir Lispro Lispro Lispro Aspart, Aspart, Aspart, or Plasma insulin Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs Glulisine Glulisine Glulisine

52. Insulin Requirements in Health and Illness Relative Proportion of Insulin Requirement (%)* *Estimations for illustrative purposes: requirements may vary widely. Clement S, et al. Diabetes Care. 2004;27:553–591. Illness-Related HealthySick/ Eating Sick/ NPO

53. Converting from IV to SC insulin l Establish 24 hr Insulin Requirement –Extrapolate from average over last 6-8 hr if stable l Give One-Half Amount As Basal l Give One-Half Amount As Total Bolus –Give post meal based on portion of food consumed or –Give 1.5 units Rapid-acting for every CHO consumed l Monitor a.c. tid, hs, and 3 am l Correction Bolus for All BG >140 mg/dl

54. Correction Bolus (Supplement) l Must determine how much glucose is lowered by 1 unit of rapid-acting insulin l This number is known as the correction factor (CF) l Use the 1700 rule or Weight to estimate the CF l CF = 1700 divided by the total daily dose (TDD) [ex: if TDD = 50 units, then CF = 1700/50 = ~30 meaning 1 unit will lower the BG ~30 mg/dl ] l CF = 3000 divided by Weight in kg

55. Correction Bolus Formula Example: –Current BG:250 mg/dl –Ideal BG: 100 mg/dl –Glucose Correction Factor: 30 mg/dl Current BG - Ideal BG Glucose Correction factor 250 - 100 30 = 5.0u

58. Initiating SC Basal Bolus l Starting total dose = 0.5 x wgt. in kg Wt. is 100 kg; 0.5 x 100 = 50 units l Basal dose (glargine) = 50% of starting dose at HS 0.5 x 50 = 25 units at HS l Bolus doses (aspart / lispro) = 50% of starting dose 0.5 x 50 = 25 divided by 3 = ~8 units pc (tid) l Correction bolus = (BG - 100)/ CF, where CF = 1700/total daily dose; CF = 30

59. Protocol for Treatment of Hypoglycemia l Any BG <80 mg/dl: D50 = (100-BG) x 0.4 ml IV l Recheck in 15 minutes and retreat if needed l If eating, may use 15 gm of rapid CHO (prefer glucose tablets) (prefer glucose tablets) l Do Not Hold Insulin When BG Normal

60. TPN or Enteral Feedings l Determine insulin requirement via IV Insulin needs l For TPN, add insulin to TPN bag with correction SC every 4 to 6 hours l For enteral feedings, give Glargine every 12 hours or NPH every 8 hours or Regular every 6 hours with correction SC every 4 to 6 hours.

64. Hospital Diabetes Plan What Can We Do For Patients Admitted To Hospital? l Pathway Protocols For All Hyperglycemia and Diabetes Patients l Finger Stick BG ac qid on ALL Admissions with BG >140 mg/dL or history of DM or high risk (ICU, Cardiac, Vascular, CVA, etc) l Check All Steroid Treated Patients l Diagnose Diabetes FBG >126 mg/dl Any BG >200 mg/dl

65. Hospital Diabetes Plan What Can We Do For Patients Admitted To Hospital? l Document Diagnosis in Chart Hyperglycemia Is Diabetes Until Proven Bring to All Physicians Attention Note on Problem List and Face Sheet l Check Hemoglobin A1C in all hyperglycemic patients l Hold Metformin; Hold TZD with CHF l Start Insulin in All Hospitalized Patients with BG >140 mg/dl

66. l Treat Any Patient With BG >140 mg/dl With Insulin –Treat Any BG >140 mg/dl with Rapid-acting Insulin (BG-100) / (3000 / wt kg) or 1700 / total daily insulin –Treat Any Recurrent BG >180 mg/dl with IV Insulin if failing SC therapy or >110 to 140 mg/dl if NPO, acute MI, perioperative, ICU, or >100 mg/dl if pregnant l If More than 0.5 u/hr IV Insulin Required with Normal BG Start Long Acting Insulin Hospital Diabetes Plan Protocol for Insulin in Hospitalized Patient

67. Hospital Diabetes Plan Protocol for Insulin in Hospitalized Patient Hospital Diabetes Plan Protocol for Insulin in Hospitalized Patient l Daily Total: Pre-Admission or Weight (kg) x 0.5 u –50% as Glargine (Basal) –50% as Total Rapid-acting insulin (Bolus) Give in Proportion to Meals CHO EatenGive in Proportion to Meals CHO Eaten l BG >140 mg/dl: (BG-100) / CF CF = 1700 / Total Daily Insulin or 3000 / Wt (kg) Do Not Use Sliding Scale As Only Diabetes Management

68. Hospital Diabetes Plan What Can We Do For Patients Admitted To Hospital? l Get Diabetes Education Consult l Instruct Patient in Monitoring and Recording See That Patient Has Meter on Discharge l Decide on Case Specific Program for Discharge l Arrange Early F/U with PCP

69. Conclusion l Our journey is not over, it has only begun l We must normalize glucose in all hospital patients l By implementing, assessing and revising protocols/pathways for hyperglycemic management, we can achieve this ultimate goal of normal glycemia

70. For Further Information l Guidelines –American Academy of Clinical Endocrinology: www.aace.com/pub/ICC/inpatientStatement l Protocols –Georgia Hospital Association: www.gha.orgwww.gha.org –Atlanta Diabetes Associates: www.adaendo.comwww.adaendo.com –Glucommander: www.glucommander.com