4/10/2015. Foundations to Managing Inpatient Hyperglycemia. Learning Objectives

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1 Foundations to Managing Inpatient Hyperglycemia Module A 1 Learning Objectives Develop strategies to identify patients with hyperglycemia or diabetes in the inpatient setting Establish glycemic goals to minimize episodes of hyperglycemia and hypoglycemia in your institution Compare and contrast sliding-scale insulin (SSI) therapy with scheduled subcutaneous (SC) insulin therapy Outline processes and procedures to ensure appropriate glycemic management in the inpatient setting 2 Trends in Glycemic Control Over a 2-year Period in 126 US Hospitals; Improvements in Non-ICU Patients 3 Point-of-care blood glucose (POC BG) test results at 126 hospitals Patient-days (%) >200 > >200 >250 >300 >350 >400 Bersoux S et al. J Hosp Med. 2013;8(3): Journal of Hospital Medicine by John Wiley & Sons. Reproduced with permission of John Wiley & Sons in the format Republish in continuing education materials via Copyright Clearance Center Glucose Level (mg/dl)

2 Glycemic Control in Hospitals in the United States Patient-days (%) Hyperglycemia prevalence (>180 mg/dl) Hypoglycemia prevalence (<70 mg/dl) 0 ICU Non-ICU 49,191,313 POC-BG measurements (12,176,299 ICU and 37,015,014 non-icu values) were obtained from 3,484,795 inpatients (653,359 in the ICU and 2,831,436 in non-icu areas). Swanson CM et al. Endocr Pract. 2011;17(6): Hyperglycemia During Hospitalization and Poor Outcomes in Numerous Settings: A Few Examples Citation Patient Population Significant Hyperglycemia-related Outcomes 1 Total parenteral nutrition (TPN) Mortality risk, pneumonia risk, acute renal failure 2 Noncardiac surgery Mortality risk, surgery-specific risk 3 Aneurysmal subarachnoid hemorrhage Mortality risk, impaired prognosis 4 Critically injured trauma patients LOS, mortality risk, ventilator time, infection 5 Chronic obstructive pulmonary disease (COPD) LOS, mortality risk, adverse outcomes 6 Community-acquired pneumonia LOS, mortality risk, complications 1. Pasquel FJ et al. Diabetes Care. 2010;33(4): Frisch A et al. Diabetes Care. 2010;33(8): Schlenk F et al. Neurocrit Care. 2009;11(1): Bochicchio GV et al. J Trauma. 2007;63(6): Baker EH et al. Thorax. 2006;61(4): McAllister FA et al. Diabetes Care. 2005;28(4): 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 hours Check A1C level BG monitoring A1C level 6.5% POC BG = point-of-care blood glucose testing. 6 2

3 Causes of Hospital-related Hyperglycemia Known diabetes (uncontrolled, undertreated) Undiagnosed diabetes Stress hyperglycemia (transient physiologic response to the stress of acute illness or injury) Iatrogenic (corticosteroids, catecholamines, parenteral and enteral nutrition, reduced exercise) 7 Patient Example: Severe Hyperglycemia on Admission in a Patient With Diabetes 59-year-old obese male patient with prior history of T2DM controlled on metformin, glipizide, and sitagliptin; admitted to the critical care unit with sepsis On presentation BG = 329 mg/dl BP = 108/56 mm Hg HR = 95 bpm Respiration = 18 breaths per minute Patient weight = 220 lb; height = 5 10 ; BMI = 31.6 kg/m 2 How would you manage this patient? BG = blood glucose; BMI = body mass index; BP = blood pressure;hr = heart rate; T2DM = type 2 diabetes mellitus. 8 Insulin is the Most Appropriate Agent for Critically Ill Patients Most potent glucose-lowering agent Critically Ill Patients IV Insulin Rapidly effective Easily titratable (up or down) No real contraindications Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4): American Diabetes Association. Diabetes Care. 2009;32(suppl 1):S1 S

4 Current Recommendations for Hospitalized Patients: Critically Ill Patients Hyperglycemia BG level mg/dl Intravenous insulin preferred Hypoglycemia Reassess the regimen if BG level is <100 mg/dl Modify the regimen if BG level is <70 mg/dl Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4): Admission Orders All patients with diabetes admitted to the hospital should have their diabetes clearly identified in the medical record All patients with diabetes should have an order for blood glucose monitoring, with results available to all members of the health care team American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14 S A1C Testing 12 Consider obtaining an A1C level in patients with: diabetes admitted to the hospital if the result of testing in the previous 2 3 months is not immediately available risk factors for undiagnosed diabetes who exhibit hyperglycemia in the hospital Examples of when results may be inaccurate Recent blood transfusion Hemoglobinopathy Certain anemias Splenectomy ESRD (especially if on erythropoietin-based therapy) Pregnancy ESRD = end-stage renal disease. American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14 S80. Schnipper JL et al. Endocr Pract. 2010;16(2):

5 Patient Example: Severe Hyperglycemia on Admission in a Patient With Diabetes A1C ordered Results are 8.8% Admission glucose was 329 mg/dl Given 3 units of regular insulin IV push Started on regular insulin 3 units/hour Standard drip 100 units/100 ml 0.9% NaCl BG monitoring every 1 hour until stable, then q 2 hours Once the patient is stable, will be moved out of the ICU and will begin scheduled meals 13 Insulin Infusion Protocols Published protocols vary by Patient characteristics Target glucose level Time to achieve target glucose level Incidence of hypoglycemia Rationale for adjusting the rates of insulin infusion Methods of BG measurements To determine insulin infusion protocol for an institution, evaluate Type of patients in critical care units Mean baseline glucose levels Available resources Krikorian A et al. Curr Opin Clin Nutr Metab Care. 2010;13(2): Nazer LH et al. Endocr Pract. 2007;13(2): 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):

6 Sources of Insulin Protocols American Association of Clinical Endocrinologists Society of Hospital Medicine ign/html/12clinical_tools/04_insulin_ordersiv.cfm 16 Successful Implementation of Protocols Successful implementation of protocols requires: Buy-in from key stakeholders (critical care physicians, house staff, nursing, pharmacy, hospital administration, etc) Appropriate education through in-servicing of hospital staff Ongoing monitoring of results Support from endocrinologists for specific questions or when a patient does not respond to the protocol as expected It is important to keep in mind that these algorithms have not been directly compared in clinical trials. 17 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):

7 TRANSITION FROM IV TO SC INSULIN 19 Considerations for Transition From IV to SC Insulin Which patients on IV insulin will need a transition to scheduled SC insulin? T1DM T2DM on insulin prior to admission T2DM (or new hyperglycemia ) requiring 2 units/hour of insulin T1DM = type 1 diabetes mellitus. 20 Transition From IV Insulin to SC Insulin IV insulin should be transitioned to SC basal-bolus insulin therapy When patient begins to eat and BG levels are stable Because of short half-life of IV insulin, SC basal insulin should be administered at least 1 2 hours prior to discontinuing the drip If short-acting insulin also administered, IV insulin may be able to be stopped sooner, eg, after 1 hour 21 7

8 Calculating the SC Insulin Dose Establish the 24-hour insulin requirement by extrapolating from the average IV insulin dose required over the previous 6 8 hours (if stable) Take 80% of the total daily dose (TDD) and give one half as an intermediate-acting or long-acting insulin for basal coverage and one half as a short-acting or rapid-acting insulin in divided doses before meal (If patient is not eating, just give intermediate/longacting insulin.) 22 Basal-bolus Insulin Regimen in Noncritically Ill Patients Starting insulin calculate TDD as follows: U/kg/day in patients >70 years and/or GFR <60 ml/min 0.4 U/kg/day if BG between 140 and 200 mg/dl and not meeting above criteria 0.5 U/kg/day if BG between 201 and 400 mg/dl and not meeting above criteria Distribute 50% of TDD as basal insulin and 50% as nutritional insulin: Give basal insulin (glargine/detemir) once daily or NPH twice daily at the same time each day Give nutritional insulin (rapid-acting insulin analog) in 3 divided doses before each meal, so long as consistent carbohydrate intake is ensured. Hold if patient is not able to eat Provide supplemental (correction) insulin in addition to basal and nutritional Adjust insulin dose(s) according to results of bedside BG measurements GFR = glomerular filtration rate. 23 Current Recommendations for Hospitalized Patients: Noncritically Ill Patients Hyperglycemia Random: <180 mg/dl Premeal: <140 mg/dl Scheduled SC insulin preferred SSI discouraged Hypoglycemia Reassess the regimen if BG level is <100 mg/dl Modify the regimen if BG level is <70 mg/dl Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):

9 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 Clement S et al. Diabetes Care. 2004;27: Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4): 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 Plasma Insulin ( U/mL) 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, :00 12:00 16:00 20:00 24:00 4:00 8:00 Time Adapted from Bray et al Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4): Bray B. Consult Pharm. 2008;23(suppl B): Roberts G et al. Med J Aust. 2012;196(4): Umpierrez GE et al. Diabetes Care. 2011;34(2): 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 They are produced by recombinant DNA (rdna) technology 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 27 9

10 Basal Analogs Offer Advantages Theoretical insulin profile 1 Serum Insulin Level 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): Tanwani LK. Am J Geriatr Pharmacother. 2011;9(11): Advantages of Rapid-acting Insulin Analogs Relative Insulin Effects Theoretical insulin profile 1 * Rapid-acting insulin analogs Regular Human Insulin (RHl) Time (hours) 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 * Theoretical representations of insulin levels over time. Adapted from Freeman JS Freeman JS. J Am Osteopath Assoc. 2009;109(1): Tanwani LK. Am J Geriatr Pharmacother. 2011;9(11): Handelsman Y et al; AACE Task Force for Developing Diabetes Comprehensive Care Plan. Endocr Pract. 2011;17(suppl 2): Insulin Analogs First Generation Rapid Acting Insulin lispro Insulin aspart Insulin glulisine Long Acting Insulin glargine Insulin detemir Second Generation Rapid Acting FIAsp (NN1218) insulin* aspart with addition of L-arginine and nicotinamide as an absorption modifier Long Acting Glargine U-300 Insulin degludec* PEGylated insulin lispro (LY )* *Investigational, not approved by the FDA

11 Time-action Profiles of Available Insulin Products Insulin aspart, insulin glulisine, insulin lispro 4 6 hours Regular 6 8 hours NPH hours Plasma Insulin Levels Insulin glargine, insulin detemir up to 24 hours Hours Hirsch IB. N Engl J Med. 2005;352: The New England journal of medicine by MASSACHUSETTS MEDICAL SOCIETY Reproduced with permission of MASSACHUSETTS MEDICAL SOCIETY, in the format reuse in CME materials via Copyright Clearance Center. 31 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 32 Supplemental Insulin Scale BG (mg/dl) Insulin-sensitive Usual Insulin-resistant > > 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 33 11

12 Sliding-scale Insulin (SSI) 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): Hirsch IB. JAMA. 2009;301(2): 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 = 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 ( ). A Blood Glucose (mg/dl) B Blood Glucose (mg/dl) * Randomization * Breakfast * Duration of Treatment (days) * * * Lunch Dinner Bedtime Duration of Treatment (days) Umpierrez G E et al. Diabetes Care. 2011;34(2): 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. 35 RABBIT-2 Surgery: Composite Hospital Complications and Outcomes: SSI vs Basal-bolus Insulin Sliding Scale Insulin 20 Basal Bolus Insulin ICU length of stay 3.19 vs 1.23 days; P = SSI vs BB Number of patients with complications* *P = 0.003; **P = Umpierrez G E et al. Diabetes Care. 2011;34(2): Wound infections** 3 0 Pneumonia 5 1 Acute respiratory failure 4 Acute renal failure Bacteremia Mortality Postsurgery ICU admission 36 12

13 Non-insulin Therapies in the Hospital Sulfonylureas may lead to hypoglycemia if nutrition is interrupted. Metformin contraindicated in setting of altered renal function, dehydration, acidosis, hypoxia, surgery, and following the use of iodinated contrast dye. Thiazolidinediones are not rapidly effective. They are associated with edema and congestive heart failure. Incretin-based therapies (GLP-1 receptor agonists, DPP-4 inhibitors) have a greater effect on postprandial glucose so would be effective mainly in eating patients. The former are associated with nausea. There is not extensive published experience with non-insulin agents in the hospital. DPP-4 = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1. ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006;29(8): Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4): Case Study Example Moving to Stepdown Unit Patient is stable; will be moved out of the ICU and will begin scheduled meals The average dose of IV insulin was 1.5 units/hour over the past 8 hours TDD is ~40 units 80% of 40 = 32 units Basal insulin = 50% of TDD = ~16 units (glargine/detemir) Nutritional = 50% of TDD = ~5 units per meal (x 3 meals) (lispro/glulisine/aspart) Doses are then titrated against actual glucose levels. 38 Medical Nutrition Therapy (MNT) MNT should be a component of the glycemic management program for all hospitalized patients with DM and hyperglycemia Consistent amount of carbohydrates at each meal can be useful in coordinating doses of rapid-acting insulin to carbohydrate ingestion Dietitian to provide carbohydrate content of meals If amount of carbohydrates vary, fixed insulin doses will be either too much or too little, resulting in fluctuations in blood glucose levels 39 13

14 Striking the Right Balance Hyperglycemia Hypoglycemia 40 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 Documentation! 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): American Diabetes Association. Diabetes Care. 2009;31(suppl 1):S1 S 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):

15 Causes of Treatment-related Hypoglycemia Incidence percentage of proximate causes of hypoglycemia Excess insulin Inadequate monitoring Diet change Administration error Hyperkalemia treatment Physician computer entry error Elliott MB et al. J Diabetes Sci Technol. 2012;6(2): Scenarios Prompting Increased Monitoring and Possible Decreases in Insulin Dose Patient is switched to NPO status Reduction in food intake Discontinuation of enteral feeding or TPN Discontinuation or reduction in IV dextrose Timing of premeal insulin if meal disrupted due to medical procedures or patient transport Reduction in corticosteroid administration NPO = nothing by mouth; TPN = total parenteral nutrition. 44 Transition From Hospital to Outpatient Care? Preparation for transition to the outpatient setting should begin at the time of hospital admission Multidisciplinary team: bedside nurse, clinical pharmacist, registered dietitian, case manager Clear communication with outpatient providers is critical for ensuring safe and successful transition to outpatient management 45 15

16 Transition to Discharge Does patient have a glucose monitor for home use? Does patient know how to inject insulin and how to prevent and to treat hypoglycemia? Is patient clear about the diabetes therapy after discharge? Does patient have appropriate outpatient follow-up appointment with primary care or specialist? 46 Predischarge Checklist Diet information Monitor/strips & Rx Rx for/supplies of medications, insulin, needles Treatment goals Contact phone numbers Medi-Alert bracelet Survival Skills training 47 Survival Skills to Be Taught Before Discharge Basic understanding of what diabetes is How and when to take diabetes medications Basic knowledge of effect of carbohydrates on glucose levels Recognition, treatment, and prevention of hypoglycemia Self-monitoring of BG and implication of results What to do during illness How to dispose of lancets and insulin syringes Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):

17 Case Study: Severe Hyperglycemia on Admission in a Patient with Diabetes 59-year-old obese male patient with prior history of T2DM controlled on metformin, glipizide, and sitagliptin; admitted to the critical care unit with sepsis On presentation BG = 329 mg/dl BP = 108/56 mm Hg HR = 95 bpm Respiration = 18 breaths per minute Patient weight = 220 lb; height = 5 10 ; BMI = 31.6 kg/m 2 BG = blood glucose; BMI = body mass index; BP = blood pressure;hr = heart rate; T2DM = type 2 diabetes mellitus. 49 Case Study Resolution Patient prepares for discharge A1C level is 8.8% Patient was on 3 oral agents prior to hospital stay How would you manage this patient? 50 Possibilities for Discharge Hyperglycemia Regimen Based on hemoglobin A1C: Home regimen Titration of home regimen Or new insulin regimen (if last option, simple regimen with aggressive patient education and prompt follow-up) 51 17

18 Case Study Resolution Discharge plan Discuss with the patient the need for basal insulin in addition to his oral agents Educator to provide hands-on instruction on administration techniques Provide education to caregiver/family if possible Comprehensive outpatient education should be scheduled 52 Key Learning Points Insulin remains the most appropriate agent for a majority of hospitalized patients. In critically ill patients, insulin is given as a continuous IV infusion. In noncritically ill inpatients, hyperglycemia is best managed using scheduled SC basal-bolus insulin regimens supplemented with correction doses as needed and adjusted daily with the guidance of frequent BG monitoring. Prevention of hypoglycemia is equally as important to patient outcomes and is an equally necessary part of any effective glucose control program. 53 Key Learning Points Modern insulin analogs offer advantages over the older human insulins (eg, regular and NPH insulin) because their time-action profiles more closely correspond to physiological basal and prandial insulin requirements, and have a lower propensity for inducing hypoglycemia than human insulin formulations. Long-acting basal insulin analogs (glargine, detemir) are suitable and preferred for the basal component of therapy; rapid-acting insulin analogs (aspart, lispro, glulisine) are recommended for bolus and correction doses. Sliding-scale insulin (SSI) regimens are not recommended, specifically because they exclude a basal insulin component from the therapy

19 Resources American Association of Clinical Endocrinologists Inpatient Glycemic Resource Center Institute for Safe Medication Practices American Society of Hospital Pharmacists: Safe Use of Insulin in Hospitals hhtp:// Society for Hospital Medicine Resource Center miccontrol.cfm 55 19