Paul M. Szumita, PharmD BCPS Clinical Pharmacy Practice Manager Brigham & Women’s Hospital Boston, MA

1. Glucose Management for Inpatients: A multidisciplinary approach Paul M. Szumita, PharmD BCPS Clinical Pharmacy Practice Manager Brigham & Women’s Hospital Boston, MA

2. Learning Objectives • Review the benefits and risks of insulin therapy in the hospital setting • Identify the essential elements that need to be addressed when implementing a glycemic control program • Propose critical elements that should be addressed when transitioning a patient from one setting to another

3. Case 1: 60 y/o with T2DM • Home regimen • glipizide 10 mg/day, metformin 1 g bid • Admitted to GMS with CAP • Good appetite • 60 kg • Lab glucose 250 (A1C 7%), creatinine 1.0 How should this patients diabetes be Managed in-house?

4. Case 2: 65 y/o Female • 80 kg, no history of diabetes • Admitted to SICU post CAGB • First Glucose value = 153 How should this patients glucose be In-house?

5. Continuum of Risk • Clear association between hyperglycemia and bad outcome • Morbidity and mortality • So, what is the “best” glucose level? • Maximize efficacy • Minimize adverse events from both hyperglycemia and hypoglycemia

6. Intensive Insulin Therapy in Surgical/Medical ICU Patients Van den Berghe G et al. N Engl J Med. 2001; 345:1359-67. Van den Berghe G et al. N Engl J Med. 2006; 354:449-61.

7. Post hoc Analysis of Surgical ICU Mortality: Effect of Average BG BG>150 110<BG<150 p=0.0009 p=0.026 BG<110 BG = blood glucose in mg/dL Van den Berghe G et al. Crit Care Med. 2003; 31:359-66.

8. Four-Year Follow Up p Intensive Treatment Cumulative 4-Year Survival Conventional Treatment Days after ICU Admission Ingels C et al. Eur Heart J. 2006 Apr 11 [Epub ahead of print].

9. Hyperglycemia and Mortality: Intensive Care Units Mortality Rate (%) Mean Glucose Value (mg/dL) Krinsley JS. Mayo Clin Proc. 2003; 78:1471-8.

10. Non-ICU Patients • No randomized controlled trials available • Currently rely on data from observational studies • Hyperglycemia in general medical and surgical units associated with the following: • Up to an 18-fold increase in in-hospital mortality • Longer length of stay (9 vs. 4.5 days) • More subsequent nursing home care • Greater risk of infection Umpierrez GE et al. J Clin Endocrinol Metab. 2002; 87:978-82.

11. Hyperglycemia: An Independent Marker of In-Hospital Mortality in Patients withOR WITHOUT Established Diabetes Total In-patient Mortality 16.0% * Mortality (%) 3.0% 1.7% Normoglycemia Known New Diabetes Hyperglycemia * p < 0.01 Umpierrez GE et al. J Clin Endocrinol Metabol. 2002; 87:978-82.

12. Potential Benefits of Improved Inpatient Glycemic Control • Improving hyperglycemia may improve or avoid • Complications of myocardial infarction and stroke • Complications of vascular and cardiac surgery • Dehydration, venous thromboembolism (VTE), electrolyte disturbances • Gastric emptying, nausea, emesis • Infection, healing rates

13. Inpatient Target Plasma Glucose Levels (mg/dL) ACE ADA • American College of Endocrinology. Endocrine Practice 2004; 10: 77-82. • American Diabetes Association. Diabetes Care. 2008; 31:S1-S110.

14. Creating the Glycemic Target at Your Institution? • Clear association between hyperglycemia and bad outcomes… But… • Should different patients have different goals? • How long should control be maintained? • Is the glucose control or the therapeutic use of insulin responsible for beneficial effects? • What is the most effective and safest way to control glucose in different settings? • Many other questions

15. Best Practices • Glucose control teams/champions • Assess current quality • Standardized insulin protocols/order sets • Decision support for protocols • Address Safety issues • Comprehensive educational programs • Continuous quality assessment and quality improvement • Data/information sharing

16. Glycemic Control Team/Champions • Hospitalists • Pharmacists • Endocrinologists • Intensivists • Nurses • Administrator • Informatics • Food service / nutrition / diabetes educators • Local champions ACE/ADA Task Force on Inpatient Diabetes.Diabetes Care. 2006; 29:1955-62. Szumita PM. Pharmacy Times. 2007;(April):110-22.

17. Glycemic Control Team • Team will be the driving force for: • Institution’s goal/target • Ambulatory • ICU • Non-ICU • Establish policies working with hospital committees • Create/adopt protocols • QA & QI projects • Addressing safety issues • Formulary decisions • Education programs • Overcome barriers ACE/ADA Task Force on Inpatient Diabetes.Diabetes Care. 2006; 29:1955-62. Szumita PM. Pharmacy Times. 2007;(April):110-22. Shojania K. JAMA. 2006; 296 (4); 427-440

18. Assess Current Quality or“Glucometrics” • Glycemic control • A1c • Glucose • Hypoglycemia rates • Medication use patterns • Documentation and plan for improvement

19. Types of Protocols/Order Sets • Ambulatory Patients • Non-ICU SC insulin regimen order set • Non-pregnant • Pregnant/OB • Emergency Department • PACU/OR • Incorporating many different scenarios • NPO • Tube Feeds • Half meals • Full meals • TPN

20. Types of Protocols/Order Sets • DKA/HHS order set • ICU (Non-DKA/HHS) order set • IV insulin protocol • Transition to SC from IV (ICU) • Hypoglycemia order set • Transition to out-patient

21. Decision Support • Informatics solutions • Reminder “pop-ups” for patients: • With hyperglycemia  order protocol • With hyperglycemia on protocol adjust insulin dose • With hypoglycemia on protocol  adjust insulin dose • At risk for hyperglycemia  order protocol • At risk of hypoglycemia order protocol • Patient lists • By team or unit • Nurse-protocols (institution-wide) • Limits decision by team • Opt-out protocols

22. Safety Issues • Oral agents • Class side effects • Insulin is perennially on the list of medication responsible for errors in hospitals • IV Drips preparation/storage • SC insulin devices • Bar code scanning • Hypoglycemia protocol with all meds known to cause hypoglycemia • Smart pump technology • Computerized multiplication factor IV insulin protocols • Limit formulary

23. Insulin Vial to Device • 2005 ASHP Recommendations for Safe Use of Insulin in Hospitals • Floor stock insulin should be minimized or eliminated • Pharmacy should provide insulin devices or draw up individual doses of basal insulins • Enhance nurse and patient safety • “Automatic” safety needle (no recapping) • Bar-coding • Infection control issue • Economic benefit • Less waste (3 mL vs. 10 mL) American Society of Health-System Pharmacists. Available at: http://www.ashp.org/emplibrary/Safe_Use_of_Insulin.pdf

24. Education • Educate the educators to allow for local ownership • All levels and professions • MD • PA • RN • NP • RPh • Dietitians • PCA • Continuous education • Feedback with metrics and improvements initiatives • Patient education

25. Continuous quality assessment and quality improvement • Perfection may not be attainable with the first improvement project • Document incremental improvement • Pilots allows opportunities for controlled assessment in a small number of patients • Evaluate, efficacy, safety and costs of each change • Repeat • Repeat

26. Continuous quality assessment and quality improvement • Lessons learned from experience • No protocol or treatment algorithm is perfect • Goals of quality improvement: • Achieves goals better than existing practice • As safe or safer

27. Data Sharing • Share data or “metrics” of quality improvement initiatives • Diabetes committee/ Glycemic Control Team • ICU, Surgical, Hospitalists leadership • P&T committee • Nurse administration • Nurse educators • Nurse clinical practice • Bedside clinicians • Share Data via institution to institution • Publication • Colleague to colleague

28. Role of the Pharmacist • Physical/local champions • Active member of glucose control team • Political lobbying within institution • Protocol selection/development • Formulary decisions • Education • Implementation of protocols • Work with local IS teams • Bedside advocate • Safety initiatives • Quality assessment/improvement leader Szumita PM. Pharmacy Times. 2007;(April):110-22. Shojania K. JAMA. 2006; 296 (4); 427-440

29. Just Some Barriers • Lack of institutional consensus regarding goals • No standardized approach to testing and treatment • Inadequate insulin drip protocol • Non-adherence to national guidelines • Fear of hypoglycemia • Culture • POCT and lab • Communication • Health-care resources Anger KE et al. Pharmacotherapy. 2006; 26:214-28. Szumita PM. Pharmacy Times. 2007;(April):110-22. ACE/ADA Task Force on Inpatient Diabetes.Diabetes Care. 2006; 29:1955-62. Shojania K. JAMA. 2006; 296 (4); 427-440

30. Fear of Hypoglycemia • Fear of hypoglycemia may impede • Willingness of clinicians to target lower glucose values • Clinicians should fully understand • Hyperglycemia and its associated morbidity and mortality • Hypoglycemia and its associated morbidity and mortality • Risk factors for hypoglycemia • Inadequate glucose intake • Infrequent glucose monitoring • Lack of communication • Inability to report symptoms • Concomitant drug therapy • Nothing-by-mouth status • Underlying disease states Anger KE et al. Pharmacotherapy. 2006; 26:214-28.

31. Ways to AddressFear of Hypoglycemia • Address hypoglycemia in glucose management guideline • Treatment • Prevention • Guideline should have laboratory and point-of-care testing (POCT) monitoring frequencies • Instructions on how to restart insulin therapy • Education, Education, Education

32. Overcoming Barriers • Multidisciplinary approach • By in for all • Incorporate best practices strategies to overcome each barrier • No single barrier is impossible to overcome

33. Glycemic Control in the Hospital: Clinical

34. General Principals • Acute hyperglycemia is bad • Treating hyperglycemia in the hospital setting • Avoid oral agents • Insulin is generally the treatment of choice • Insulin in tops on the list of medication errors in hospitals • Need protocolized care throughout institution

35. Approach to Hyperglycemia in Hospitalized Patients • Inpatient situations are unstable • Change from home to inpatient regimen • No single algorithm suitable for all patients • Review BBG  adjust meds frequently • Reassess medications at dischargechange back to outpatient (home) regimen

36. Medications in the Inpatient Setting • Insulin drips • indicated for most ICU patients • Oral agents • should RARELY be used • SubQ insulin • indicated for MOST non-ICU patients

37. Creating and Implementing an Effective I.V. Insulin Protocol • American Diabetes Association (ADA) goal glucose in the ICU is less than 110 mg/dL • In the “real world,” this goal is VERY DIFFICULT

38. No Ideal Protocol in the Literature • Many have been described • Few have been rigorously evaluated • Few are designed to reach goal of 80-110 mg/dL

39. The “Fixed” Protocol

40. Intensive Insulin Therapy in Critically Ill Patients No serious hypoglycemic events. Van den Berghe G et al. N Engl J Med. 2001; 345:1359-67. Van den Berghe G et al. N Engl J Med. 2006; 354:449-61.

41. “Multiplier” Protocol Concept: A Simple Calculation • (Blood glucose – 60) X multiplication factor = new insulin infusion rate for that hour • The multiplication factor changes depending on the change in glucose value Osburne RC et al. Diabetes Educ. 2006; 32:394-403. Davidson PC et al. Diabetes Care. 2005; 28:2418-23.

42. Paper “Multiplier” Protocol Lien LF et al. Endocr Pract. 2005; 11:240-53.

43. Outcomes of Electronic “Multiplier” Protocol Davidson PC et al. Diabetes Care. 2005; 28:2418-23.

44. BHIP Protocol *Never stop the insulin. The minimum rate should be 0.5 units/hour.

45. Case 2: 65 y/o Female • 80 kg, no history of diabetes • Admitted to SICU post CAGB • First Glucose value = 153 How should this patients glucose be In-house?

46. Lessons Learned • Implement a protocol which achieves goals better than existing protocol • The new protocol has got to be safe • We need to continue to further improve protocols in the literature • Consider computer protocol No Protocol is Perfect

47. Approach to Hyperglycemia in Hospitalized Patients • Inpatient situations are unstable • Change from home to inpatient regimen • No single algorithm suitable for all patients • Review BBG  adjust meds frequently • Reassess medications at dischargechange back to outpatient (home) regimen

48. Problems with Oral Agents in the Hospital • Sulfonylureas (e.g., glyburide, glipizide, etc.) • Hypoglycemia (long acting) • ? Coronary artery disease • Metformin • Lactic acidosis risk • Renal insufficiency, hypotension, heart failure • GastrointestinaI • Nausea, abdominal pain, diarrhea • Thiazolidinediones (TZDs or “glitazones”) (e.g., rosiglitazone) • Possible liver toxicity • Fluid overload, heart failure • Inability to titrate (very slow onset of action)

49. Effective SubQ Insulin Regimens Have THREE COMPONENTS • Basal insulin • Controls fasting and pre-meal glucose • Nutritional insulin • Controls glucose from nutritional sources such as discrete meals, tube feeds, or TPN • Supplemental/Correction insulin • Used to cover unexpected hyperglycemia that was not controlled by scheduled basal and nutritional insulin

50. Summary of Three Components of Effective Insulin Regimens Programmed/Scheduled Supplemental