1. Spotlight Case May 2004 Too Tight Control: The Risks of Intensive Insulin Therapy

2. 2 Source and Credits This presentation is based on the May 2004 AHRQ WebM&M Spotlight Case in Medicine CME credit is available through the Web site See the full article at http://webmm.ahrq.govhttp://webmm.ahrq.gov –Commentary by: Haya Rubin, MD, PhD, The Johns Hopkins University; Vera Fajtova, MD, Harvard Medical School –Editor, AHRQ WebM&M: Robert Wachter, MD –Spotlight Editor: Tracy Minichiello, MD –Managing Editor: Erin Hartman, MS

3. 3 Objectives At the conclusion of this educational activity, participants should be able to: Appreciate the advantages and potential complications of intensive insulin therapy in the hospitalized patient List hospital-based safeguards available to prevent insulin-related hypoglycemia Understand the difference between efficacy and effectiveness with regards to results of clinical trials

4. 4 Case: Too Much of a Good Thing A 28-year-old man with insulin-dependent diabetes mellitus was admitted with hyperglycemia and an infected foot ulcer. Due to new hospital initiatives aimed at tighter glucose control, he was started on an insulin drip rather than subcutaneous (SQ) insulin. The patient eventually required 8 units of regular insulin per hour to maintain a fingerstick glucose in the 180-220 mg/dL range.

5. 5 Adverse Effects of Hyperglycemia Hyperglycemia > 200 mg/dL is associated with more infections in patients undergoing “clean” surgery In vitro, ambient glucose > 200 mg/dL reduces macrophage migration and phagocytosis Pomposelli JJ, et al. J Parenter Enteral Nutr. 1998;22:77-81; Rayfield EJ, et al. Am J Med. 1982;72:439-50.

6. 6 Intensive Insulin Therapy in the Critically Ill Patient Wound infection rate decreased from 3% to 1% using nurse-managed IV insulin protocol to keep blood glucose < 200 mg/dL for 72 hours after heart surgery Furnary AP, et al. Ann Thorac Surg. 1999;67:352-62.

7. 7 Intensive Insulin Therapy in the Critically Ill Patient 1500 critically ill patients randomized to: –Intensive insulin therapy IV drip for BG > 110 mg/dL, goal 80-110 –Traditional insulin therapy IV insulin reserved for BG > 215 mg/dL Decreased morbidity and mortality in intensive insulin group Van den Berghe G, et al. N Engl J Med. 2001;345:1359-67.

8. 8 Conventional vs. Intensive Therapy Van den Berghe G, et al. N Engl J Med. 2001;345:1359-67.

9. 9 SQ Insulin for Non-Critically Ill Patients Physiologic control of glucose requires basal insulin and supplementation with fast-acting agent with meals New insulin analogs meet both basal and mealtime insulin needs –Daily insulin Glargine for basal (no adjustment for NPO status) –Insulin Aspart or Lispro with meals adjusted for nutritional intake

10. 10 IV intensive insulin therapy may result in more frequent hypoglycemia The use of intensive IV insulin has NOT been examined in the non-critically ill population IV Insulin for Non-Critically Ill Patients

11. 11 Case (cont.): Too Much of a Good Thing On hospital day 2, orthopedic surgery evaluated the patient and decided the wound needed surgical debridement. The orthopedic resident notified the cross-covering medicine resident that the patient would go to the OR the next day. In preparation for surgery, the orthopedic service made the patient “NPO after midnight.” At 2 am, when the nurse came to measure the hourly fingerstick, the patient was somnolent, tremulous, and diaphoretic, with a fingerstick glucose of 20 mg/dL.

12. 12 What Went Wrong? Communication breakdown Efficacy vs. Effectiveness

13. 13 Communication Breakdown Orthopedic surgery wrote the NPO order; medicine wrote the insulin drip order Having multiple providers write orders can result in errors and poor outcomes –Delays in diagnosis or treatment –Unnecessary or duplicative testing Potential role of hospitalist in streamlining order writing and communication Pollack MM, et al. Crit Care Med. 2003:31:1620-9; Wachter RM. Ann Int Med. 1999;130:338-42.

14. 14 Efficacy vs. Effectiveness Clinical trials often achieve lower rates of adverse events than seen in practice –Patients rarely monitored as closely outside of trial –Clinicians may apply therapy to patients excluded from trials Broadening inclusion criteria can lead to a lesser benefit in actual practice (effectiveness) than that seen in the trial (efficacy) Katzan IL, et al. JAMA. 2000;283:1151-8.

15. 15 Intensive Insulin Therapy in the Non- Critically-Ill Patient? Hypoglycemia is most common complication of any insulin therapy Oral intake in the perioperative population is variable increasing risk of hypoglycemia Clinical trials thus far have used strict protocols Broad use of intensive insulin therapy outside of intensive care setting requires safeguards be put in place

16. 16 Improved Glycemic Control as a Quality Improvement Measure Most quality improvement efforts focused on the “underuse” of effective therapies Institute for Healthcare Improvement suggests monitoring a single, central outcome to help make QI projects practical Must remember to consider the potential adverse effects of increased use and increase monitoring/surveillance accordingly The Institute for Healthcare Improvement Web siteThe Institute for Healthcare Improvement Web site; QualityHealthCare.org Web site. QualityHealthCare.org Web site

17. 17 Intensive Insulin Therapy in the Non- Critically-Ill Patient Protocols should clearly outline: –Drip adjustment at specific blood glucose levels –Alterations in rate and IV fluid type if patient is NPO –Frequency of glucose monitoring Lillis K. Health Manag Technol. 2003;24:36-7; Bradley EH, et al. Jt Comm J Qual Saf. 2003;29:409-15.

18. 18 Potential Interventions to Improve Safety of Intensive Insulin Therapy Automated order sets and preprinted order sheets –Effective in reducing medication errors related to chemotherapy dosing –Effective in ensuring appropriate therapy for myocardial infarction in emergency departments Where CPOE available, standard order sets for all patients with diabetes or with IV insulin drip ordered Automatic adjustments to drip and/or MD notification of change to NPO status (forcing function) Lillis K. Health Manag Technol. 2003;24:36-7; Bradley EH, et al. Jt Comm J Qual Saf. 2003;29:409-15; Farbstein K, Clough J. Jt Comm J Qual Improv. 2001;27:123-37.

19. 19 The patient was treated with 1 ampule of D50 and his insulin drip was held. He recovered completely from this event. Case (cont.): Too Much of a Good Thing

20. 20 Take-Home Points Both IV and SQ insulin can be safe and effective in controlling blood glucose in hospitalized patients when standard protocols are followed Recent data support the practice of tighter control with IV insulin in the surgical ICU –Unclear if these results generalize to patients outside of the ICU Safety in clinical trials differs from safety in practice

21. 21 Take-Home Points Insulin drip protocols that have been tested should be implemented hospital-wide Various strategies (standard order sets, decision support, computerized forcing functions) can help prevent adverse events Quality improvement efforts that focus on “tight control” of physiologic parameters must incorporate efforts to monitor and prevent the most common adverse events of over-treatment