Hyperglycemia in Hospitalized Patients

1. Robert J. Rushakoff, MD Associate Clinical Professor of Medicine University of California, San Francisco robert.rushakoff@ucsf.edu Hyperglycemia in Hospitalized Patients • Strategies For Implementing Change • Nuts and bolts of management

2. Strategies For Implementing Inpatient Glycemic Control www.rushakoff.com www.endotext.com

3. "Each blind man perceived the elephant as something different: a rope, a wall, tree trunks, a fan, a snake, a spear..."

4. Patient Assessment of Skills, Education Diabetes Assessment Form 1.----------------------------------------------------------------------------- 2.----------------------------------------------------------------------------- 3.----------------------------------------------------------------------------- 4.----------------------------------------------------------------------------- 5.----------------------------------------------------------------------------- 6.----------------------------------------------------------------------------- 7.----------------------------------------------------------------------------- 8.----------------------------------------------------------------------------- 9.----------------------------------------------------------------------------- 10.---------------------------------------------------------------------------- 11.---------------------------------------------------------------------------- 12.---------------------------------------------------------------------------- 13.---------------------------------------------------------------------------- 14.---------------------------------------------------------------------------- 15.---------------------------------------------------------------------------- 16.---------------------------------------------------------------------------- 17.---------------------------------------------------------------------------- 18.---------------------------------------------------------------------------- 19.---------------------------------------------------------------------------- 20.---------------------------------------------------------------------------- 21.---------------------------------------------------------------------------- 22.---------------------------------------------------------------------------- 23.---------------------------------------------------------------------------- Page 1 of 6 Medical Errors JCAHO Coordination of Outpatient Care Home care services Outpatient diabetes classes Jargon CQI ICU Protocols

5. What is inpatient diabetes care? X Primary Diabetes Education RARE Diabetes as Primary Diagnosis X Diabetes Metabolic Floors

6. Benefits of Improved Diabetes Management • Outpatient • DCCT • UKPDS (United Kingdom Prospective Diabetes Study) • Blood pressure control • Lipids • Inpatient/perioperative - ????????

7. Target Glucose Levels Alive

8. Target Glucose Levels No DKA or Hyperosmolar Coma

9. Target Glucose Levels Occasional hypo- and hyperglycemia

10. Target Glucose Levels No hypo- or hyperglycemia • Prevent fluid and electrolyte abnormalities secondary to osmotic diuresis • Improve WBC function • Improve gastric emptying • Decrease surgical complications • Earlier hospital dischange • Decreased post-MI mortality • Decreased post-CABG morbidity and mortality

11. Target Glucose Levels Normal Glucoses Decreased Morbidity and Mortality

12. Problems With High Glucoses

13. Increased Infections Early postoperative glucose control predicts nosocomial infections rate in diabetic patients Pomposelli et al: J Parenteral Ent Nut. 1998; 22:77-81 • Relative risk for “serious” postop infections increased to 5.7 when glucose >220 mg/dl

14. Increased Infections Relative Odds of Wound Infections 121-206 -------207-229 1.17230-252 1.86 253-3531.78 (p<0.05 for upward trend) Perioperative Glycemic Control and the Risk of Infectious Complications in a Cohort of Adults with Diabetes Golden et al: Diabetes Care, 22:1408, 1999 411 diabetics who underwent CABGLeg and chest wounds, pneumonia and UTI

15. Glucose and post-CABG morbidity and mortality Diabetes and Coronary Artery Bypass Surgery. An examination of perioperative glycemic control and outcomes Diabetes Care 2003; 26:1518-1524 • Retrospective Review of 291 patients surviving 24 h post op • 40% with retinopathy, nephropathy or neuropathy Inpatient Complications For each 1 mmol/l (18 mg/dl) increase in postop day 1 over 6.1 mmol/l (110 mg/dl), a 17% increase risk of complications

16. Length of Stay University Healthsystem ConsortiumDiabetes ManagementFinal Data Analysis Report 6/4/1999 IN-CONTROL: glucose 60-250 mg/dlFLUCTUATING: glucose <60 or >250 mg/dl Primary Diagnosis: AMI Length of Stay* In-control (N=26) 4.1 Fluctuating (N=59) 6.7 * (p<0.05)

17. Length of Stay University Healthsystem ConsortiumDiabetes ManagementFinal Data Analysis Report 6/4/1999 IN-CONTROL: glucose 60-250 mg/dlFLUCTUATING: glucose <60 or >250 mg/dl Primary Diagnosis: CABG Length of Stay* In-control (N=18) 6.3 Fluctuating (N=143) 8.2 * NS

18. Length of Stay University Healthsystem ConsortiumDiabetes ManagementFinal Data Analysis Report 6/4/1999 IN-CONTROL: glucose 60-250 mg/dlFLUCTUATING: glucose <60 or >250 mg/dl Primary Diagnosis: CAP Length of Stay* In-control (N=19) 4.5 Fluctuating (N=56) 6.3 * (p<0.05)

19. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes • Retrospective Review • Hyperglycemia in 38% • 26% known diabetes • 12% no known diabetes • Mortality New hyperglycemia 16% Known Diabetes 3% Nondiabetics 1.7% J. Clin Endocrinol. 2002;87:978-982.

20. TPN: Adverse Outcomes Hyperglycemia Is Associated With Adverse Outcomes in Patients Receiving Total Parenteral Nutrition Cheung et al: Diabetes Care, 28:2367-2371, 2005 Risk of complications in relation to mean daily blood glucose level

21. Risk of Complications by glucose level quartile after adjusting for age, sex and presence of preexisting diabetes Cheung et al: Diabetes Care, 28:2367-2371, 2005

22. Intervention Studies

23. Decreased post-CABG morbidity and mortality Intensive Intervention by a Diabetes Team Diminishes Excess Hospital Mortality in Patients with diabetes who undergo CABG Kalin et al. Diabetes Suppl. 47:A87 1998 Diabetes team followed patientPerioperative IV insulin infusionAlgorithm based SQ premeal insulin Mortality during CABG 1993-96 Relative risk National 1.46Beth Israel 1.02

24. Decreased post-MI mortality Effects of insulin treatment on cause-specific one year mortality and morbidity in diabetic patients with acute myocardial infarction. DIGAMI Study Group. Malmberg et al. Eur Heart J 1996 PeriMI IV insulin infusionAlgorithm based SQ premeal insulin for 1 year Mortality (%) 1 year3.4 years Control 26 44 Insulin 19 33

25. DIGAMI2 (European Heart J. Prepublication Feb 2005) • Group 1 – IV insulin then long term SQ insulin • Group 2 – IV insulin then standard treatment • Group 3 – Standard treatment Mortality

26. Decreased Infections Insulin infusion improves neutrophil function in diabetic cardiac surgery patients. Rassias AJ, Marrin CA, Arruda J, Whalen PK, Beach M, Yeager MP. Anesth Analg 1999; 88:1011-6. Perioperative IV insulin infusion Neutrophil phagocytic activity % baseline Control 47 Insulin 75

27. Decreased Infections Glucose control lowers the risk of wound infection in diabetics after open heart operations Zerr et al: Ann Thoracic Surgery, 1997, 63:356-61Furnary et al. Annals of Thoracic Surgery 1999, 67:352-60Furnary et al. J Thoracic Cardiovascular Surgery 2003, 125: 1007-1021 Perioperative IV insulin infusionProtocol to maintain glucoses <200 Incidence of Deep Wound Infections (%) 19971999 Routine Control 2.4 2.0“Tight” Control 1.5 0.8

28. Decreased Infections Glucose control decreases mortality in diabetics after open heart operations Furnary et al. J Thoracic Cardiovascular Surgery 2003, 125: 1007-1021 14.5% 6.0% 4.1% 2.3% 1.3% 0.9%

29. Decreased Morbidity and Mortality Intensive Insulin Therapy in Critically Ill Patients. Van den Berghe G, Wouters P, Weekers F, et al. N Engl J Med 2001; 345:1359-1367. Patients (all) on mechanical Ventilation in ICU Randomly assigned to IV insulin maintaining glucoses between 80-110 mg/dl or conventional treatment (iv insulin if glucose >215 mg/dl then maintain glucose between 180-200.) % given Insulin24 hour doseAM glucose Intensive 99 71U 103 Conventional 39 33U 153

30. Decreased Morbidity and Mortality 12 month mortality Intensive 4.6% Conventional 8.6% Main effect on patients in ICU >5 days Intensive Insulin Therapy in Critically Ill Patients. Van den Berghe G, Wouters P, Weekers F, et al. N Engl J Med 2001; 345:1359-1367. Patients (all) on mechanical Ventilation in ICU Randomly assigned to IV insulin maintaining glucoses between 80-110 mg/dl or conventional treatment (iv insulin if glucose >215 mg/dl then maintain glucose between 180-200.)

31. Decreased Morbidity and Mortality Intensive Insulin Therapy in Critically Ill Patients. Van den Berghe G, Wouters P, Weekers F, et al. N Engl J Med 2001; 345:1359-1367. Patients (all) on mechanical Ventilation in ICU Randomly assigned to IV insulin maintaining glucoses between 80-110 mg/dl or conventional treatment (iv insulin if glucose >215 mg/dl then maintain glucose between 180-200.) • Intensive Treatment reduced: • In hospital mortality 34% • Sepsis 46% • Need for dialysis 41% • Number of transfusions 44%

32. Decreased Morbidity and Mortality Intensive Insulin Therapy in Critically Ill Patients. Van den Berghe G, Wouters P, Weekers F, et al. N Engl J Med 2001; 345:1359-1367. Patients (all) on mechanical Ventilation in ICU Randomly assigned to IV insulin maintaining glucoses between 80-110 mg/dl or conventional treatment (iv insulin if glucose >215 mg/dl then maintain glucose between 180-200.) • Unresolved Questions: • Application in medical ICU patients • Application in children in ICU • Application in surgical patients in regular wards

33. Kaplan-Meier Curves for In-Hospital Survival Van den Berghe, G. et al. N Engl J Med 2006;354:449-461

34. Intensive insulin therapy in patient with severe sepsis and septic shock is associated with an increased rate of hypoglycemia Multicenter German study (the VISEP trial), designed to randomize 600 subjects with medical or surgical severe sepsis to conventional or intensive insulin therapy, was stopped after recruitment of 488 subjects because of no difference in mortality (21.9 vs. 21.6%, p = 1.0) and frequent hypoglycemia in the intensive insulin therapy arm (12.1 vs. 2.1%, p < 0.001) [abstract]. Brunkhorstet al Infection 2005;33:19–20.

35. Hawthorne Effect Initial improvement in a process of production caused by the obtrusive observation of that process.

36. Hawthorne Effect Tight glucose control = investigator commitment and bedside presence, more tests, more attention, more patient visits, more interventions and overall better care

37. Pending Studies NICE-SUGAR 2 multicenter prospective studies Australia and New Zealand Intensive Care Society and the Canadian Critical Care 5000 patients GLUControl Europe 3500 patients

38. AACE Position Statement: Hospital Glycemic Goals Intensive Care Units: 110 mg/dL Non-Critical Care Units: Pre-Prandial 110 mg/dL Max. Glucose 180 mg/dL

39. How to Obtain “Tight” Control • Bedside glucose monitoring • IV insulin drips • Diabetic Flow sheets • Discourage the use of traditional Sliding Scale insulin

40. INSULIN SLIDING SCALE

41. INSULIN SLIDING SCALE

42. Roller Coaster Effect of Insulin Sliding Scale

43. Mr. And Mrs. XXXXX are admitted for Sweet Sixteenitis. Mr. XXXXX has Type 2 diabetes and takes a total of 75 Units insulin per day (2 shots). Glucoses at home are “poorly controlled.” Mrs. XXXXX also has Type 2 diabetes but she has good control taking about 25 units of Lispro premeal and 40 Units NPH at night.

44. Fingerstick qid with regular insulin SQ coverage: FSBG Action < 50 1 amp D50 iv and call HO 51-80 give juice and repeat in 0.5-1 hr 81-200 no coverage 201-250 3U regular insulin SQ 251-300 6U regular insulin SQ 301-350 8U regular insulin SQ 351-400 10U regular insulin SQ >400 12U regular insulin SQ, call HO

45. Advice: May need to increase doses for patients who are septic or treated with steroids (insulin resistance) Hyperglycemia is better than hypoglycemia Patients appreciate changing to FSBG qd once their insulin requirements are established Endocrinologists absolutely HATE sliding scales. They are not meant to treat diabetes, but exist merely to prevent hypoglycemia. Do not discharge patients on insulin sliding scales; instead, find an appropriate outpatient regimen before discharge.

46. Action Without BenefitThe Sliding Scale of Insulin UseSawin, Arch Int Med 157:489, 1997 • Routine multiple measurements of capillary blood glucose levels, along with sliding scale insulin doses, offer no benefit to sick patients with diabetes, and when such patients come to the hospital, they need to follow their previous treatment of insulin or an oral hypoglycemic drug. • Burden of proof is on those who continue to use a sliding scale regimen • Use of sliding scale insulin…had best be avoided

47. INSULIN SLIDING SCALE

48. Postoperative Problems • Stress induced counterregulatory hormones • Varying rates of IV dextrose • Unpredictable eating patterns • Lack of established predictors of insulin needs

49. Optimal Regimen • Target glucose range that would minimize risk of hypoglycemia and avoid undesirable effects of hyperglycemia • Fixed dextrose infusion to reduce chances of hypoglycemia • Simple algorithm for individualizing the rate of the insulin infusion

50. Postoperative Management of Diabetes Mellitus(Diabetes Care 10:722, 1987) Protocol 1. D5 1/2 NS with 20 meq KCl/l at 100 cc/h 2. Insulin 1.5 U/h IV 3. BS checked q2h 4. --- <80 mg/dl: decrease insulin by 0.5 U/h give 25 ml IV 50% dextrose --- 80-119: decrease insulin by 0.5 U/h --- 120-180: no change --- 181-240: increase insulin by 0.5 U/h --- >240: increase insulin by 0.5 U/h and 8 U IV bolus