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Management of Diabetes and Hyperglycemia in the Hospital Patient: Focus on subcutaneous insulin use in the non-critically ill, adult patient Lead authors: Gregory Maynard MD, MS David H. Wesorick MD For the SHM Glycemic Control Task Force The SHM Glycemic Control Task Force Hospitalists Representing The Society of Hospital Medicine: Gregory Maynard, MD Alpesh Amin, MD, MBA, FACP Lakshmi Halasyamani, MD Kevin Larsen, MD Cheryl O'Malley, MD Jeffrey L. Schnipper, MD, MPH David H. Wesorick, MD Mitchell J. Wilson, MD Education Marcia D. Draheim, RN, CDE Sharon Mahowald, RN, CDE Pharmacy Stuart T. Haines, Pharm.D., FASHP, FCCP, BCPS Representing the American Society of Consultant Pharmacists: Donald K Zettervall, RPh, CDE, CDM Case Management Endocrinologists Representing the American Diabetes Association: Andrew J. Ahmann, MD Michelle F. Magee, MD Representing the American Association of Clinical Endocrinologists: Richard Hellman, MD, FACP, FACE Representing the American College of Physicians Doron Schneider, MD Endocrinology Expert Panel: Susan Shapiro Braithwaite, MD, FACP, FACE Mary Ann Emanuele, MD, FACP Irl B. Hirsch, M.D. Robert Rushakoff, MD Representing the Case Management Society of America Cheri Lattimer, RN, BSN Nancy Skinner, RN, CCM Dietetics Carrie Swift, MS, RD, BC-ADM Visit the Society of Hospital Medicine’s Glycemic Control Resource Room at www.hospitalmedicine.org for more Information on the Task Force Members. Objectives For This Exercise • Appreciate the obstacles to achieving good glycemic control in hospital patients • Understand and apply the best practice of inpatient hyperglycemia/diabetes management using subcutaneous insulin, including the use of anticipatory, physiologic insulin dosing in a variety of clinical situations • Understand the common deviations from the best practices of insulin management in the hospital • Learn how to prevent and manage hyperglycemia and hypoglycemia Managing Diabetes in the Hospital Presents Different Challenges than Managing Diabetes in the Outpatient Arena! The hospital is associated with: - Nutritional and clinical instability The need for changes from the home diabetes medical regimen Acute illness, “stress-related” hyperglycemia Use of medications that impact glycemic control Why Should We Care? • Hyperglycemia occurs frequently in hospital patients, and is associated with poor outcomes • Hypoglycemia occurs frequently in hospital patients, and is unpleasant and dangerous • Adequate metabolic control is an attainable goal for hospital patients Hyperglycemia is Undesirable! Umpierrez et al. Journal of Clinical Endocrinology and Metabolism 2002; 87: 978-82. • Hyperglycemia in the hospital is associated with adverse outcomes • Hyperglycemia can occur in patients without a known diagnosis of diabetes – Undiagnosed diabetes – Illness-related hyperglycemia • Patients with hyperglycemia without a known diagnosis of diabetes experienced even worse outcomes than the known diabetes patients in this study Hyperglycemia and Poor Hospital Outcome Metabolic stress response stress hormones and peptides Glucose Insulin Reactive O2 species Immune dysfunction Infection dissemination FFA Ketones Lactate Secondary mediators Cellular injury/apoptosis Inflammation Tissue damage Altered tissue wound repair Clement et al, Diabetes Care 27:553-591, 2004 Transcription factors Prolonged hospital stay Disability / Death Hyperglycemia is Undesirable! • Epidemiologic and uncontrolled observational studies suggest that hyperglycemia is associated with adverse outcomes in a wide range of hospital patients • Interventional trials have shown that improved glycemic control is associated with improved outcomes in several different patient populations, including those with: – Acute myocardial infarction – Cardiac surgery – Critical illness • The evidence supporting metabolic control in inpatients has been reviewed (Diabetes Care 2004; 27: 553-91, Endocrine Practice 2004; 10: 77-82, and Diabetes Care 2006; 29: 1955-62) How Can Diabetes and Hyperglycemia be Controlled in the Hospital? • Oral agents = often inappropriate for hospital patients • IV insulin = most often used in the intensive care unit setting (or in other defined populations) • Subcutaneous insulin = the drug of choice for controlling hyperglycemia in the majority of non-critically ill patients Oral Antidiabetes Agents in the Hospital • Oral agents can be continued in stable patients with normal nutritional intake, normal blood glucose levels, and stable renal and cardiac function. However, there are several potential disadvantages to using these medications in hospital patients: – Disadvantages of most oral agents: • Slow-acting/difficult to titrate – Disadvantages of insulin secretagogues (e.g. sulfonylureas and meglitinides such as glyburide, glypizide, repaglinide, etc.): • Hypoglycemia if caloric intake is reduced • Some are long-acting (hypoglycemia may be prolonged) – Disadvantages of metformin: • Lactic acidosis can occur when used in the setting of renal dysfunction, circulatory compromise, or hypoxemia • Slow onset of action • GI complications: Nausea, diarrhea Oral Antidiabetes Agents in the Hospital, continued… – Disadvantages of thiazoladinediones (e.g. rosiglitazone, pioglitazone): • Slow onset of action (2-3 weeks) • Can cause fluid retention (particularly when used with insulin), and increase risk for CHF – Disadvantages of alpha-glucosidase inhibitors (e.g. acarbose, miglitol) • Abdominal bloating and flatus • Need pure glucose to treat hypoglycemia – Disadvantages of GLP-1 mimetics (e.g. exenatide) • Newer agents without data to support use in the hospital • Abdominal bloating and nausea secondary to delayed gastric emptying Diabetes and Hyperglycemia Require Proactive Management • Diabetes requires proactive management in all hospital patients. There are no “autopilot” insulin regimens • Insulin is a “high alert” medication that is frequently associated with medication errors in the hospital, and JCAHO considers insulin to be one of the highest risk medications in the hospital (JCAHO Website, 2006) The Issue of Hypoglycemia • Fear of hypoglycemia often results in the use of nonphysiologic insulin regimens (e.g. sliding scale insulin, alone) • Using too little insulin and purposefully allowing hyperglycemia would only be appropriate if hyperglycemia were entirely benign or if adequate metabolic control were an unattainable goal • It has been demonstrated that rates of hypoglycemia in the hospital can be reduced by using standardized, physiologic insulin regimens What is the Appropriate Glycemic Control Target for Inpatients? • Controversial! ICU Non-ICU, Preprandial Non-ICU, Maximum ACCE/ACE 110 mg/dl 110 mg/dl 180 mg/dl ADA 110 mg/dl 90-130 mg/dl 180 mg/dl Selecting a Non-ICU Glycemic Target For Your Practice/Institution • Examples of target ranges set by some institutions: – 90-150 mg/dL – Pre-prandial target 90-130 mg/dL; Random glucose < 180 mg/dL – Pre-prandial target 80-130 mg/dL for most patients; preprandial target 90-150 mg/dL for patients with hypoglycemia risk factors Current Practice ≠ “Best Practice” • Dependence on non-physiologic insulin prescribing (as opposed to insulin that mimics physiologic insulin secretion) • Dependence on reactive strategies (e.g. sliding-scale insulin) • Overemphasis on simplicity (particularly simplicity from the perspective of the ordering physician) • Overemphasis on avoidance of hypoglycemia • Lack of standardization of insulin use in the hospital What is the “Best Practice” for Managing Diabetes and Hyperglycemia in the Hospital? • The answer is anticipatory, physiologic insulin dosing, prescribed as a basal/bolus insulin regimen • This means giving the right type of insulin, in the right amount, at the right time, to meet the insulin needs of the patient The Components of a Physiologic Insulin Regimen • Basal insulin • Nutritional insulin • Correctional insulin Physiologic Insulin Secretion: Basal/Bolus Concept Nutritional (Prandial) Insulin Insulin (µU/mL) 50 25 Basal Insulin 0 Breakfast Glucose (mg/dL) 150 Lunch Supper Nutritional Glucose 100 50 0 Suppresses Glucose Production Between Meals & Overnight Basal Glucose 7 8 9 101112 1 2 3 4 5 6 7 8 9 A.M. P.M. Time of Day The 50/50 Rule Providing Exogenous Basal Insulin • Long-acting, non-peaking insulin is preferred as it provides continuous insulin action, even when the patient is fasting • Required in ALL patients with type 1 diabetes • Many patients with type 2 diabetes will require basal insulin in the hospital • Can be estimated to be about 1/2 of the total daily dose of insulin (TDD) Which Insulins are Best for Basal Coverage? Insulin Effect NPH Detemir (Levemir) Glargine (Lantus) Regular Lispro (Humalog) Aspart (Novolog) Glulisine (Apidra) Inhaled insulin 0 6 12 Time (hours) 18 24 Providing Exogenous Nutritional Insulin • Usually given as rapid-acting analogue (preferred in most cases) or regular insulin, for those patients who are eating meals • Must be matched to the patient’s nutrition • Should not be given to patients who are not receiving nutrition (e.g. NPO) • Can be estimated to be about ½ of the total daily dose of insulin (TDD) Which Insulins are Best for Nutritional Coverage? Insulin Effect NPH Detemir (Levemir) Glargine (Lantus) Regular Lispro (Humalog) Aspart (Novolog) Glulisine (Apidra) Inhaled insulin 0 6 12 Time (hours) 18 24 Providing Exogenous Correctional Insulin • Correctional insulin is extra insulin that is given to correct hyperglycemia • Usually rapid-acting or regular insulin (usually the same as the nutritional insulin) • Often written in a “stepped” format that is used in addition to basal and nutritional insulin • Customized to the patient using an estimate of the patient’s insulin sensitivity • If correctional insulin is required consistently, or in high doses, it suggests a need to modify the basal and/or nutritional insulin doses Using Exogenous Insulin to Imitate Physiologic Insulin Secretion: Summary • Basal insulin: Use non-peaking, longer acting insulins – Glargine or detemir are preferred – NPH also possible • Nutritional insulin: Depends on the type of nutrition – Rapid-acting insulin is preferred when patients are eating meals – Regular insulin also possible • Correctional insulin: Use rapid-acting (or regular) insulin – Usually the same as the nutritional insulin Which Patients Should be Treated with a Physiologic Insulin Regimen? During hospitalization • Any patient with blood glucose levels consistently above the target range Immediately at the time of admission • All patients with type 1 diabetes • Patients with type 2 diabetes if… – They are known to be insulin-requiring – They are known to be poorly controlled despite treatment with significant doses of oral agents – They are known to require high doses of oral agents that will be held in the hospital A Stepwise Approach to Physiologic Insulin Dosing in the Hospital 1. Estimate the amount of insulin the patient would need over one day, if getting adequate nutrition = Total Daily Dose (TDD) 2. Assess the patient’s nutritional situation 3. Decide which components of insulin the patient will require, and which percentage of the TDD each should represent 4. Assess blood glucoses at least daily, adjusting insulin doses as appropriate STEP 1: Estimate the Amount of Insulin the Patient Would Need Over One Day, If Getting Adequate Nutrition = Total Daily Dose (TDD) • Insulin drip-based estimate (for patients treated with an insulin infusion- see below) • For patients already treated with insulin, consider the patient’s preadmission subcutaneous regimen and glycemic control on that regimen • Weight-based estimate: – TDD = 0.4 units x Wt in Kg – Adjust down to 0.3 units x Wt in Kg for those with hypoglycemia risk factors, including kidney failure, type 1 diabetes (especially if lean), frail/low body weight/ malnourished elderly, or insulin naïve patients – Adjust up to 0.5-0.6 units (or more) x Wt in Kg for those with hyperglycemia risk factors, including obesity and high-dose glucocorticoid treatment Conditions Associated with Hypoglycemia in Hospitalized Patients • Known sensitivity to insulin recognized as low TDD of insulin (e.g. type 1 diabetes) or lean body habitus • Malnutrition or low body weight • Specific medical conditions, including renal failure (ESRD), liver disease, heart failure, malignancy, circulatory failure (shock), adrenal insufficiency, burns, alcoholism • Prior hypoglycemia or labile blood glucose control • Medications: sulfonylureas, pentamidine, quinine, or lowering of the doses of glucocorticoids • Decreases in nutritional intake (e.g. those related to physician orders, delays in food delivery, sudden discontinuation of parenteral or enteral nutrition, or patientspecific factors such as nausea, etc) • Advanced age Conditions Associated with Hyperglycemia in Hospitalized Patients • Known insulin resistance recognized by high TDD of insulin or obesity • Medications: glucocorticoids, catecholamines, tacrolimus, cyclosporine • Significant illness: “Stress response” related to the release of counter-regulatory hormones • Increases in nutritional intake (e.g. restarting a diet, starting enteral or parenteral nutrition) STEP 2: Assess the Patient’s Nutritional Situation • Eating meals or receiving bolus tube feeds • Eating meals but with unpredictable intake • Getting continuous tube feeds • Getting tube feeds for only part of the day • Getting parenteral nutrition • NPO STEP 3: Decide Which Components of Insulin the Patient Will Require, and Which Percentage of the TDD Each Should Represent • Basal insulin can generally be estimated to be 1/2 of the TDD • Nutritional insulin makes up the remaining 1/2 of the TDD STEP 3: Decide Which Components of Insulin the Patient Will Require, and Which Percentage of the TDD Each Should Represent, Continued… • In most cases, basal insulin should be provided • In most cases, well-designed corrective insulin regimens should be provided • When a patient is not receiving nutrition, nutritional insulin should not be given • Nutritional insulin needs must be matched to the actual nutritional intake STEP 4: Assess Blood Glucoses at Least Daily, Adjusting Insulin Doses as Appropriate • Blood glucose targets can only be achieved via continuous management of the insulin program • There is no “autopilot” insulin regimen for a hospitalized patient! Example Cases • Introduction to the Cases Case 1 56 year old woman with DM2 admitted with a diabetes-related foot infection which may require surgical debridement in the near future, eating regular meals. - Weight: 100 kg - Home medical regimen: Glipizide 10 mg po qd, Metformin 1000 mg po bid, and 20 units of NPH q HS - Control: A recent HbA1c is 10%, POC glucose in ED 240 mg/dL What are your initial orders for basal and nutritional insulin? How would you manage the oral agents? Case 1: Solution • Bedside glucose testing AC and HS • Discontinue oral agents • Total daily dose 100 kg x 0.6 units/kg/day = 60 • Basal: Glargine 30 units q HS • Nutritional: Rapid-acting analogue 10 units q ac at the first bite of each meal • Correction: Rapid-acting analogue per scale q ac and HS (Note: Use correctional insulin with caution at HS, reduce the daytime correction by up to 50% to avoid nocturnal hypoglycemia) Case 1 Continued… The patient is made NPO after midnight for a test, but is expected to be able to resume her diet at lunch or dinner the next day. What changes would you make to her management program regarding glucose monitoring and her insulin program? Would you provide dextrose in her IV fluids? Case 1 continued: Solution • Change bedside glucose checks to q 6 hours, as the patient will not be eating meals • Continue basal insulin: If using glargine, continue as is. If using NPH, continue in equal twice daily doses with a dose reduction of 1/3-1/2 while NPO. • Hold nutritional insulin while NPO • Provide a low level of intravenous dextrose (e.g. 75-125 cc/hr of a D5 containing solution) • Continue appropriate correctional insulin for hyperglycemia Case 2 56 year old woman with type 1 diabetes admitted with a diabetesrelated foot infection. The wound is an infected ulcer on the fifth digit with necrosis. The plan is for amputation first thing in the morning, so the patient will be NPO after midnight. However, she is expected to resume a regular diet at lunch the following day after surgery. - Weight: 70 kg - Home medical regimen: 70/30 insulin 14 units BID - Control: A recent HbA1c is 9%, POC glucose in ED is 240 mg/dL It is now dinner time, and the patient took her last dose of insulin before breakfast. What insulin would you give her now (before dinner) and how would you modify her regimen given the plan for NPO after midnight? Case 2: Solution • Bedside glucose testing AC and HS while eating, and q 6 hours when NPO • TDD by weight = 70 kg x 0.4 units/kg/day = 28 units • Her home TDD is 28, but patient has very poor control on this regimen, so increase (arbitrarily) by 20% = 34 units • IV dextrose infusion while NPO (e.g. D5 at 75-150 cc/hr) • Basal: Glargine 17 units q HS • Nutritional: Rapid-acting insulin 6 units q ac at the first bite of each meal • Correction: Rapid-acting insulin per scale q ac and HS Case 3 A 54 yo m with DM2 presents with acute pancreatitis (1 Ranson criteria). You make him NPO as part of your plan. - Weight: 100 kg (BMI 35) - Home medical regimen: 70/30 insulin 15 units at breakfast and 15 units at dinner - Control: A recent HbA1c was 9.2%, admission glucose is 166 What insulin orders would you write? Case 3: Solution • Bedside glucose checks Q6 hrs • TDD = 100kg x 0.5 = 50 • Basal: Glargine 25 units HS • Nutritional: None (NPO) • Appropriate correctional insulin scale • D5 ½ NS at 100 cc/hr continuous Case 3 Continued… Hospital day 3, the patient’s abdominal pain is worse, although he is otherwise stable. You decide to start TPN. The patients blood glucoses have been in the mid to high 100’s on the initial insulin regimen described above (see next slide). How would you manipulate this patient’s insulin as you initiate TPN? Prior Day Glucose 8 AM Noon Supper Bedtime 150 195 172 198 Insulin Totals Lispro Mealtime Lispro Correctional Glargine TDD 2u 2u 2u 6u 25 u 25 u 31 u Case 3 Continued: Solution • Parenteral nutrition often causes hyperglycemia and often requires insulin treatment, even in patients who would not require insulin otherwise • An intravenous insulin infusion, separate from the nutritional infusion, is a rational way of managing this patient that will allow good initial control of the patient’s blood glucose, and accurate insulin dose-finding • Stop SC insulin when starting the insulin infusion Case 3 Continued… Initially the insulin drip is adjusted frequently but, after 6 hours, stabilizes to a steady state, using 2-3 units per hour. Over the subsequent 12 hours the patient uses 31 units of insulin total (see next slide). You want to try to discontinue the separate intravenous infusion. How much insulin do you put in the TPN bag for the subsequent day? What other orders do you write to assure that hyperglycemia does not ensue? 8 AM Prior Day Glucose Noon Supper Bedtime Glucoses averaging 130 over last 12 hours Insulin totals Lispro Mealtime Lispro Correctional Glargine Infusion TDD 2-3 units per hour for a total of 31 units over the last 12 hours 62 u 62 u Case 3 Continued: Solution • Add the majority (e.g. 80%) of the patients daily insulin to the next 24 hour bag = 48 units regular insulin (31 units in 12 hours x 2 = 62 x 0.8 = 48) • In addition, appropriately dosed correctional insulin, given SC, with glucose checks every 4-6 hours would be appropriate Case 4 A 62 y/o woman with a history of type 2 diabetes was admitted to the ICU with urosepsis. Her admission glucose was 311 and her admission systolic blood pressure was 60. Over the first day, she was treated with IV fluids, antibiotics, an IV insulin infusion, and pressors (which were weaned off after a few hours). She stabilized and was able to eat a small amount of dinner that evening. On the morning of the second hospital day, she remains stable and the ICU team calls you to transfer this patient out of the ICU to your service. You decide to change her to a subcutaneous insulin program. - Weight: 90 kg - Home medical regimen: 70/30 NPH/regular insulin 10 units BID - Control: She says that her outpatient blood glucoses are usually in the 200’s, but she does not know her HbA1c level. Her insulin and glycemic data for the prior day are shown on the next slide. What subcutaneous insulin orders would you write? Time 10 Events Admit Glucose 311 201 154 134 118 98 112 Insulin Drip Rate 6u 4u 3u 2u 2u 1u 2u Time 11 12 13 14 15 16 17 18 19 20 108 188 211 155 1u 3u 4u 3u Dinner 21 22 23 00 1 2 3 4 5 6 7 Glucose 119 X 110 98 X 109 119 104 98 110 120 Insulin Drip Rate 2u 2u 1u 1u 1u 1u 2u 1u 1u 1u 2u Meals Stepwise Approach to Moving from IV to SC Insulin • Calculate how much IV insulin the patient has been requiring • Recognize which component of the physiologic insulin requirement the IV insulin represents, and translate that to a SC regimen • Consider any nutritional changes that may be implemented at the time of the transition off of the drip • Make sure SC insulin is given before discontinuation of the IV insulin Case 4 Solution • TDD prior to admission = 20 (Poor control) • Weight-based TDD = 45 (90 x 0.5) • Drip-based estimate: 1 unit/hr estimate of basal needs while fasting overnight x 20 = 20 units basal insulin. Therefore, TDD estimate = 40 units • Her condition is improving, therefore her insulin requirements may decrease • Glucose check AC and HS • Basal: Glargine 20 units daily • Nutritional: rapid-acting analogue 7 units with meals • DC the insulin drip an appropriate time after the subcutaneous insulin is administered Case 4 Continued… The patient receives basal insulin at bedtime and the insulin infusion is discontinued. She is scheduled to receive 7 units of a rapid-acting insulin with each meal. The next morning her breakfast tray arrives, and the bedside glucose is 112. The nurse calls you because the patient says she does not feel like can eat much of the food that is being provided. The nurse asks if you still want the patient to receive the 7 units of rapidacting insulin. What is your response? Case 4 Continued: Solution = Post-Meal Rapid Acting Analogue • The ideal solution in this case is to have the nurse give the patient a chance to eat, and then reassess her caloric intake. The rapid-acting insulin can then be given immediately after the patient eats, in a dose proportional to the amount of carbohydrates consumed. Case 5 You are consulted by the neurology service for diabetes management on a 79 y/o M who suffered a large stroke, leaving him with severe dysphagia. He has type 2 diabetes, on maximum doses of metformin, glipizide, and rosiglitazone at home. A PEG was placed and he is up to his goal of 60 cc/hr on continuous tube feeds, but is now hyperglycemic (see next slide). - Weight: 100 kg (BMI 35) - Current medical regimen: “High” sliding-scale (orals all held) - Control: Glucoses consistently in the mid to high 200’s, a recent HbA1c is 9.6% What insulin regimen will you choose? Does the distinction between basal and nutritional insulin still make sense with continuous feeding? Prior Day Glucose 8 AM Noon Supper Bedtime 254 295 238 291 Insulin Total Lispro Mealtime Lispro Correctional 8u 8u 6u 8u 30 u Glargine TDD ? Case 5: Solution • TDD = 100 x 0.6 units/kg/day = 60 units • Provide this TDD to meet basal and continuous nutritional insulin requirements • There is no scientific evidence suggesting one way is better than another • Examples: – – – – – – – Glargine 60 units daily Glargine 24 units daily (basal) + rapid-acting insulin 6 units q4 hrs (nutritional) Glargine 24 units daily (basal) + regular 9 units q6 hrs (nutritional) 70/30 20 units q8 hrs Regular insulin 15 units q6 hrs Rapid-acting insulin 10 units q 4 hrs Other combinations Transitioning to the Outpatient Arena • Deciding on a home regimen – HbA1c – Anticipating clinical improvement – Patient factors: Financial, social, abilities, wishes • Patient education – Changes made in the hospital – Diabetes/insulin survival skills • Communication with outpatient physicians Systems for Improving the Quality of Insulin Use in Inpatients • Protocols • Standardized order sets • Physician, midlevel provider, and nurse education Summary Understanding these basic principles of physiologic, anticipatory insulin will allow clinicians to formulate rational insulin regimens in virtually any clinical situation! A printable summary sheet can be accessed via a link located in the “Teaching and Learning” section of the Glycemic Control Resource Room, just below the link you used to access this presentation. Key Review Articles • Clement and colleagues. Diabetes Care 2004; 27: 553-91. • American College of Endocrinology Position Statement on Inpatient Diabetes and Metabolic Control. Endocrine Practice 2004; 10: 77-82. • American College of Endocrinology and American Diabetes Association Consensus Statement on Inpatient Diabetes and Glycemic Control. Diabetes Care 2006; 29: 1955-62.