HAP PA-HEN Achieving More Together Managing Hyperglycemia in the Hospital: Strategies for Safe and Effective Care Pennsylvania Patient Safety Authority
Managing Hyperglycemia in the Hospital: Strategies for Safe and Effective Care Scott R. Drab, PharmD, CDE, BC-ADM Director, University Diabetes Care Associates Associate Professor of Pharmacy & Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh, Pennsylvania 2
Learning Objectives Describe the current guidelines for treating hyperglycemia in critically ill and non-critically ill patients Develop strategies to prevent hypoglycemia in the inpatient setting Outline processes and procedures for an appropriate transition from the hospital to outpatient care 3
Patients with Unknown Diabetes are a Significant Percentage ICU Admissions 15,737 patients in 9 ICUs Patients with diabetes had significantly more glycemic control challenges than patients without diabetes 5,635 patients diabetes diagnosis in ICU 1,460 (26%) of these had unknown diabetes and were: 41.0% of patients with an hemoglobin A1c > 6.5% 9.3% of all ICU patients. Higher likelihood of requiring an insulin infusion (44.3% vs 29.3%; p<0.0001) Higher average blood glucose (172 vs 126 mg/dl; p<0.0001) More hyperglycemia (19.7% vs 7.0%; blood glucose > 180 mg/dl; p<0.0001) More hypoglycemia (8.9% vs 2.5%; blood glucose < 70 mg/dl; p<0.0001), Higher glycemic variability (55.6 vs 28.8, average of patient SD of glucose; p<0.0001) Compared to patients without diabetes, patients with diabetes had significantly higher risk of mortality (13.8% vs 11.4%; p = 0.01) Carpenter DL, et al. Crit Care Med. 2015;43(12):e541-550. 4
Causes of Hospital-related Hyperglycemia Text boxes with % s can be animated Known diabetes (uncontrolled, undertreated) 70-80% of patients with diabetes and critical illnesses, and cardiac surgery have hyperglycemia Undiagnosed diabetes Stress hyperglycemia (transient physiologic response to the stress of acute illness or injury) Iatrogenic (corticosteroids, catecholamines, parenteral and enteral nutrition, reduced exercise) ~33% of patients have significant hyperglycemia without diabetes Corsino L et G, et al., In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-2014. Available at http://www.ncbi.nlm.nih.gov/books/nbk279093/?report=printable. Accessed December 29, 2015. 5
Patient-days (%) Glycemic Control in Hospitals* in the United States 35 32.2 30 25 20 28.2 Hyperglycemia prevalence (>180 mg/dl) Hypoglycemia prevalence (<70 mg/dl) 15 10 5 5.6 6.1 0 ICU Non-ICU *N=635 A total of 51,375,764 POC-BG measurements (non-icu, 39,197,762; ICU, 12,178,002) from 2,612,966 patients (non-icu, 2,415,209; ICU, 575,084) Bersoux S et al. Endocr Pract. 2015;21(9):986-992. 6
Uncontrolled Hyperglycemia is Associated with Poorer Outcomes in Hospitalized Patients in Different Clinical Situations Significant Hyperglycemia-related Outcomes Clinical Situations Mortality risk Total parenteral nutrition 1 Noncardiac surgery 2 Critical care 3 Cardiac surgery 4,5 Aneurysmal subarachnoid hemorrhage 6 Chronic obstructive pulmonary disease 7 Surgery-specific risk, surgical complications Noncardiac surgery 2 Critical care 3 Infections Total parenteral nutrition 1 Cardiac surgery 4,5 Critically injured trauma patients 8 Length of stay Critically injured trauma patients 7 Chronic obstructive pulmonary disease 8 Community-acquired pneumonia 9 Impaired prognosis/adverse outcomes (e.g., complications, renal failure, ventilator time, etc.) Total parenteral nutrition 1 Aneurysmal subarachnoid hemorrhage 6 Chronic obstructive pulmonary disease 8 Community-acquired pneumonia 1. Pasquel FJ et al. Diabetes Care. 2010;33(4):739 741. 2. Frisch A et al. Diabetes Care. 2010;33(8):1783 1788. 3. Falciglia M et al. Crit Care Med. 2009;37(12):3001-3009. 4. Furnary AP et al. J Thorac Cardiovasc Surg. 2003;125(5):1007-1021. 5. Furnary AP et al. Ann Thorac Surg. 199;67(2)352-360. 6. Schlenk F et al. Neurocrit Care. 2009;11(1):56 63. 7. Baker EH et al. Thorax. 2006;61(4):284 289. 8. Bochicchio GV et al. J Trauma. 2007;63(6):1353 13587. 9. McAllister FA et al. Diabetes Care. 2005;28(4):810 815. 7
Diagnosis and Recognition of Hyperglycemia and Diabetes in the Hospital Setting Admission Assess all patients for a history of diabetes Obtain laboratory BG testing on admission No history of diabetes BG <140 mg/dl No history of diabetes but BG >140 mg/dl History of diabetes Initiate POC BG monitoring according to clinical status Start POC BG monitoring x 24 48 hours Check A1C level BG monitoring A1C level 6.5% POC BG = point-of-care blood glucose testing. Umpierrez GE et al; Endocrine Society. J Clin Endocrinol Metab. 2012;97(1):16 38. 8
Current Recommendations for Hospitalized Patients All critically ill patients in intensive care unit settings BG level 140 180 mg/dl Pre-meal: < 140 mg/dl Intravenous insulin preferred Non critically ill patients Random: < 180 mg/dl Scheduled SC insulin preferred Sliding-scale insulin discouraged Hypoglycemia Reassess the regimen if BG level is < 100 mg/dl Modify the regimen if BG level is < 70 mg/dl AACE and ADA Consensus Statement on Inpatient Statement on Inpatient Glycemic Control. Endocr Pract. 2009;15:353 369. Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Setting: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2012;97:16 38. 9
Insulin is the Preferred Treatment for Hyperglycemia in the Hospital Setting Critically ill patients in the ICU Use IV insulin infusion to treat persistent hyperglycemia Non-critically ill patients Scheduled subcutaneous insulin therapy with basal, nutritional, and correctional components ICU=intensive care unit; IV=intravenous Handelsman Y, et al. Endocrine Practice. 2015;21(suppl 1):1-87.; Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):353 369. American Diabetes Association. Diabetes Care. 2009;32(suppl 10 1):S1 S110.
Why Insulin is the Most Appropriate Agent for Critically Ill Hospitalized Patients Most potent glucose-lowering agent Critically Ill Patients IV Insulin Rapidly effective Easily titratable (up or down) No significant contraindications Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):353 369. American Diabetes Association. Diabetes Care. 2009;32(suppl 1):S1 S110. 11
Successful IV Insulin Protocol Reaches and maintains BG successfully within a prespecified target range Includes a clear algorithm for making temporary corrective changes in the IV insulin rate as patient requirements change Incorporates the rate of change in BG, not just the absolute values Incorporates the current IV insulin rate Minimizes hypoglycemia; provides specific directions for its treatment when it occurs Provides specific guidelines for timing and selection of doses for the transition to SC insulin Does your institution have an IV insulin protocol in place? Clement S et al. Diabetes Care. 2004;27(2):553 591. 12
Safe Use of IV Insulin Therapy Insulin infusion concentrations and protocols should be standardized within a hospital. All MDs/RNs should be trained with competence and assessed regularly. Accurate bedside BG monitoring done hourly (and if stable, every 2 hours). Potassium should be monitored and given if necessary. Clement S et al. Diabetes Care. 2004;27(2):553 591. 13
Pharmacological Treatment of Hyperglycemia in Non- ICU Setting Antihyperglycemic Therapy SC Insulin Recommended for most medical-surgical patients OADs Not Generally Recommended Continuous IV Infusion Selected medical-surgical patients ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006 & 2009 Umpierrez et al, Endocrine Society Non-ICU Guideline. J Clin Endocrinol Metabol. 97: January 2012 Smiley et al. HospMed. 2010;5:212 217. 14
Plasma Insulin ( U/mL) Basal-bolus Therapy Is Effective for the Maintenance of Glycemic Control Effective insulin therapy may contain basal, bolus, and supplemental doses to achieve target goals. 1 75 50 25 Breakfast Lunch Dinner Bolus (nutritional) insulin Basal insulin Correction insulin Basal-bolus is more effective at glycemic control vs SSI therapy in medical and surgical patients. 3,4 0 0 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time Adapted from Bray et al. 2 1. Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):353 369. 2. Bray B. Consult Pharm. 2008;23(suppl B):17 23. 3. Roberts G et al. Med J Aust. 2012;196(4):266 269. 4. Umpierrez GE et al. Diabetes Care. 2011;34(2):256 261. 15
SC Insulin Administration Scheduled (SSI only uses this component) Correction Basal Bolus (Nutritional) Correction Total daily insulin needs Basal Nutritional Long-acting insulin Rapid-acting insulin Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):353 369. Clement S et al. Diabetes Care. 2004;27:553 591. 16
SC Correction Insulin Algorithms Does NOT replace scheduled insulin Rather, it corrects for changing needs Based on the insulin sensitivity of the patient Inferred from total daily insulin requirement, or Inferred from weight/bmi Utilize same rapid-acting analog as that of the nutritional (bolus) insulin Need rapid onset and short duration of action Umpierrez GE et al; Endocrine Society. J Clin Endocrinol Metab. 2012;97(1):16 38. 17
Supplemental Insulin Scale BG (mg/dl) Insulin-sensitive Usual Insulin-resistant >141 180 2 4 6 181 220 4 6 8 221 260 6 8 10 261 300 8 10 12 301 350 10 12 14 351 400 12 14 16 >400 14 16 18 The numbers in each column indicate the number of units of regular or rapid-acting insulin analogs per dose. Supplemental dose is to be added to the scheduled insulin dose. Give half of supplemental insulin dose at bedtime. If a patient is able and expected to eat all or most of his/her meals, supplemental insulin will be administered before each meal following the usual column dose Start at insulin-sensitive column in patients who are not eating, elderly patients, and those with impaired renal function Start at insulin-resistant column in patients receiving corticosteroids and those treated with more than 80 U/day before admission Custom scales can be created, however, they are not the norm Umpierrez GE et al; Endocrine Society. J Clin Endocrinol Metab. 2012;97(1):16 38. 18
Why Not Sliding Scale Insulin? Definition Use of a mealtime insulin, typically regular insulin, as the sole insulin for managing a patient s diabetes Potential problems Poor control of hyperglycemia (does not address basal insulin needs) Insulin stacking Hypoglycemia Not preferred method of SC insulin delivery American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14 S80. Browning LA, Dumo P. Am J Health Syst Pharm. 2004;61(15):1611 1614. Hirsch IB. JAMA. 2009;301(2):213 214. 19
Blood Glucose (mg/dl) Blood Glucose (mg/dl) Glucose Levels During Basal-bolus and SSI Treatment Changes in BG concentration after the first day of treatment with basal-bolus with glargine once daily plus glulisine before meals ( ) and with SSI 4 times daily ( ). *P <0.001, P = 0.02, P = 0.01. A 220 200 180 160 140 * * B 120 Randomization 220 1 2 3 4 5 6 7 8 9 Duration of Treatment (days) Glucose levels before meals and bedtime. Premeal and bedtime glucose levels were higher throughout the day in the SSI group ( ) compared with basal-bolus regimen ( ). 200 180 160 140 * * * * 120 Breakfast Lunch Dinner Bedtime Duration of Treatment (days) Umpierrez G E et al. Diabetes Care. 2011;34(2):256 261. Diabetes care by AMERICAN DIABETES ASSOCIATION Reproduced with permission of AMERICAN DIABETES ASSOCIATION. in the format Republish in continuing education materials via Copyright Clearance Center. 20
RABBIT-2 Surgery: Composite Hospital Complications and Outcomes: SSI vs Basal-bolus Insulin 30 25 26 Sliding Scale Insulin 20 Basal Bolus Insulin 19.6 15 ICU length of stay 3.19 vs 1.23 days; P = 0.003 SSI vs BB 11 11 12.5 10 9 5 0 Number of patients with complications* 3 Wound infections** 3 0 Pneumonia 5 1 Acute respiratory failure 4 Acute renal failure 2 1 1 1 Bacteremia Mortality Postsurgery ICU admission *P = 0.003; **P = 0.050. Umpierrez G E et al. Diabetes Care. 2011;34(2):256 261. 21
Benefits of Insulin Analogs vs Human Insulin Insulin analogs are derivatives of human insulin that have undergone one or more chemical modifications to alter the time-action profile of the insulin Time-action profile of SC human insulin does not always match physiologic demand Insulin analogs were designed to more closely mimic normal physiologic insulin secretion patterns 22
Insulin Analogs Approved in the US Rapid Acting Insulin lispro (U-100, U- 200) Insulin aspart Insulin glulisine Long Acting Insulin detemir Insulin degludec (U-100, U-200) Insulin glargine (U-100, U- 300) 23
Serum Insulin Level Basal Analogs Offer Advantages Theoretical insulin profile 1 Basal analog NPH Compared with NPH, basal insulin analogs provide 2 : Reduced rate of hypoglycemia Once-daily dosing in T2DM Similar reduction in FPG 0 24 Time (hours) FPG = fasting plasma glucose; NPH = neutral protamine Hagedorn. 1. Brunton S et al. J Fam Pract. 2005;54(5):445 452. 2. Tanwani LK. Am J Geriatr Pharmacother. 2011;9(11):24 36. 24
Relative Insulin Effects Advantages of Rapid-acting Insulin Analogs Theoretical insulin profile 1 * Rapid-acting insulin analogs Regular Human Insulin (RHl) Compared with RHI, rapid-acting insulin analogs 2,3 : Provide a more physiologic response Have a more rapid onset and shorter duration of action Are associated with less severe episodes of hypoglycemia 0 10 20 Time (hours) * Theoretical representations of insulin levels over time. Adapted from Freeman JS. 1 1. Freeman JS. J Am Osteopath Assoc. 2009;109(1):26 36. 2. Tanwani LK. Am J Geriatr Pharmacother. 2011;9(11):24 36. 3. Handelsman Y et al; AACE Task Force for Developing Diabetes Comprehensive Care Plan. Endocr Pract. 2011;17(suppl 2):1 53. 25
Avoiding Hypoglycemia 26
Essential Part of Any Insulin Use: A Hypoglycemia Protocol Clear definition of hypoglycemia Glucose level (ADA) <70 mg/dl Nursing order to treat without delay Stop insulin infusion (if patient is on one) Oral glucose (if patient is able to take POs) IV dextrose or glucagon (if patient is unable to take POs) Repeat BG monitoring 15 minutes after treatment for hypoglycemia and repeat treatment if BG not up to target Directions for when and how to restart insulin Look for the cause of hypoglycemia and determine if changes in the antihyperglycemic treatment strategy are needed ACE/ADA Task Force on Inpatient Diabetes. Endocr Pract. 2006;12(4):458 468. American Diabetes Association. Diabetes Care. 2009;31(suppl 1):S1 S110. Umpierrez GE et al; Endocrine Society. J Clin Endocrinol Metab. 2012;97(1):16 38. 27
Hypoglycemia Orders Nurse treat per protocol, treat if bedside BG level <70 mg/dl; notify resident Juice, intravenously administered dextrose, or intramuscularly administered glucagon depending on ability to take oral nutrition and intravenous access Recheck bedside BG level in 15 minutes and repeat as necessary Adapted from Schnipper JL et al. Endocr Pract. 2010;16(2):209 218. 28
Transitions of Care 29
Transition to Outpatient Status Begin discharge planning early Stabilize blood glucose prior to discharge Obtain A1C for discharge planning if the result is not available from the previous 2 to 3 months A1C can now be used as a means to make the diagnosis of diabetes Moghissi ES, et al. Endocr Pract. 2009;15:353 369. 30
Transition to Outpatient Status Provide instruction Medication use / Injection technique if using insulin Basics on diet plan Glucose monitoring Hypoglycemia prevention and treatment Refer patient to a certified diabetes educator Clarify insurance reimbursement to ensure availability of medications at discharge Schedule a follow-up visit with clinician and provide emergency number to call if problems Moghissi ES, et al. Endocr Pract. 2009;15:353 369. 31
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