FSHP Disclosure Strategies for Glycemic Management in the Inpatient Setting: Guidelines vs. Reality Melissa Marshall, PharmD, BCPS Jeffrey Ruff, PharmD We do not have (nor does any immediate family member have) a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias our presentation. 1 2 Pharmacist Objectives 1. Identify the health consequences of uncontrolled hyperglycemia 2. Discuss the guidelines regarding inpatient management of hyperglycemia in noncritically ill patients 3. Compare treatment strategies including Basal-Bolus, Basal-Plus and Correctional 4. Identify obstacles to implementation of guideline-driven hyperglycemia management 5. Discuss strategies and options for implementation Technician Objectives Diabetes Prevalence & Burden Affects more than 340 million globally U.S. in 2012 29.1 million (9.3%); >20% of adults 1 in 3 by 2050 3-fold greater chance of hospitalization vs. no DM 7.7 million hospital stays 38% - 46% of non-critically ill hospitalized patients DM remains the 7 th leading cause of death 1. Identify the health consequences of uncontrolled hyperglycemia 2. Recall the guidelines regarding inpatient management of hyperglycemia in noncritically ill patients 3. Recognize different treatment strategies with insulin: Basal-Bolus, Basal-Plus and Correctional $176 billion (43% inpatient care) 4. Discuss key safety precautions associated with insulin use Corsino L, et al. [Updated 2014 Oct 4]. In: De Groot LJ, et al., editors. Endotext [internet]. South Dartmouth 3 (MA):MDText.com, Inc.;2000-. Available from: https://ww.ncbi.nlm.nih.gov/books/nbk279093/ 4 Pathogenesis of Hyperglycemia in the Hospital Failure to optimize insulin regimen/sole use of sliding scale Excess exogenous glucose and steroids Corticosteroids IV Dextrose Total Parenteral Nutrition Enteral Nutrition Excess stress hormones Cortisol Glucagon Catecholamines (vasopressors) Growth hormone Non-compliance to anti-diabetic regimen prior to admission Health Consequences of Hyperglycemia in the Hospital Osmotic diuresis Volume depletion/electrolyte loss Hypo-perfusion Decreased renal function Acid/base disturbances Immune system dysfunction / Inflammation Risk of infection Impaired wound healing Increased mortality Prolonged hospital stay Readmissions POOR OUTCOMES! Corsino L, et al. [Updated 2014 Oct 4]. In: De Groot LJ, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.;2000-. Available from: https://www.ncbi.nlm.nih.gov/books/nbk279093/ 2017 ISMP Guidelines for Optimizing Safe Subcutaneous Insulin Use in Adults. https://www.ismp.org/tools/guidelines/. Accessed 2017 May 18. Corsino L, et al. [Updated 2014 Oct 4]. In: De Groot LJ, et al., editors. Endotext [Internet]. South Dartmouth 5 (MA): MDText.com, Inc.;2000-. Available from: https://www.ncbi.nlm.nih.gov/books/nbk279093/ 6 1
Hyperglycemia and Adverse Events A Case for Early Detection and Prompt Glycemic Control Mortality Mortality N=6595 N=12,663 *P<0.01 Kotagal M, et al. Ann Surg. 2015 Jan;261(1):97-103. Umpierrez GE, et al. J Clin Enocrinol Metab (2002) 87(3):978-982. 7 8 Detecting Diabetes on Admission ADA recommends: A1C on admission if not performed in past 3 months Diagnostic A1C 6.5% Goal A1C ~7% Identifies High-risk patients Poorly controlled diabetics (may require treatment intensification during stay and or at discharge) Note: RBC transfusions falsely decrease A1C levels Glycemic Threshold and Targets Hyperglycemia defined as BG >140mg/dL When should insulin be started? On admission for known or newly diagnosed diabetics A1C 6.5% Persistent hyperglycemia of 180 mg/dl Target ranges (ADA, AACE) 140 180 mg/dl critically ill (A) and non-critically ill (C) Non-critically ill: Pre-meal <140 mg/dl, if hypoglycemia safely avoided (C) Magaji V, et al. Clinical Diabetes 2011; 29(1):3-9. Magaji V, et al. Clinical Diabetes 2011; 29(1):3-9. 9 10 Inpatient Glycemic Management Poor oral intake/npo 1. Basal insulin OR 2. Basal plus correctional Good nutritional intake ( basal-bolus ) 1. Basal 2. Nutritional (prandial/mealtime) and 3. Correctional insulin components Efficacy of Basal-Bolus Insulin Meta-analysis of hospitalized non-critically ill T2DM patients Basal-Bolus Insulin (BBI) versus Sliding Scale Insulin (SSI) N=12 studies systematic review; N=5 meta-analysis Study Mean Diff, 95% CI Weight Mean difference, Blood glucose (mg/dl), 95% CI Mader 2013-28.90 [-44.50, -13.30] 9.7 % Schroeder 2012-14.00 [-15.51, -12.49] 46.6 % RABBIT-2 2007-27.00 [-42.26, -11.74] 10.0 % RABBIT-2 Surg 2011-19.00 [-29.36, -8.64] 17.5 % Basal Plus 2013-16.00 [-27.04, -4.96] 16.1 % Total -17.94 [-23.37, -12.52] 100% -50-25 0 25 50 Favors BBI Favors SSI Christensen MB, et al. Diabetes Metab Res Rev. 2017;e2885. 11 12 2
Risk of Severe Hypoglycemia Basal/Bolus Regimen Most Physiologic Approach Study Risk Ratio, 95% CI Weight Risk Ratio, Hypoglycemia, BG 40 mg/dl, 95% CI Mader 2013 3.00 [0.13, 71.34] 31.5 % RABBIT-2 2007 NA (0 events) 0 % RABBIT-2 Surg 2011 9.26 [0.50, 169.82] 37.4 % Basal Plus 2013 1.55 [0.06, 37.63] 31.1 % Total 3.72 [0.63, 22.05] 100 % All had Glycemic Target (Fasting and Premeal) of 100 140 mg/dl 0.01 0.1 1 10 100 Favors BBI Favors SSI Plasma insulin μu/ml Breakfast Normal Lunch Dinner Short-acting insulin bolus Long-acting insulin insulin basal coverage profile 4am 8am Noon 4pm 8pm Midnight 4am 8am Christensen MB, et al. Diabetes Metab Res Rev. 2017;e2885. 13 Magaji V, et al. Clinical Diabetes 2011; 29(1):3-9. 14 Basal/Bolus Subcutaneous Insulin Regimen 1. Basal long-acting; covers fasting glucose produced by liver; insulin glargine (Lantus, Basaglar ), detemir (Levemir ), degludec (Tresiba ) 2. Nutritional/Prandial mealtime, bolus, rapid-acting, insulin Lispro (Humalog ), aspart (Novolog ), glulisine (Apidra ) 0 15 min. before meal Omitted if NPO 3. Correctional rapid-acting, insulin Lispro (Humalog ), aspart (Novolog ), glulisine (Apidra ) Given as a single injection along with scheduled prandial dose Based on low, med, high scale May be given with Basal insulin only for poor oral intake Inpatient Glycemic Management Total daily dose of insulin (TDDI) 1.Home dose, if controlled 2.Weight-based if insulin naïve TDDI Determination for Insulin-Naïve Patients 0.3 units/kg Underweight, older age, hemodialysis 0.4 units/kg Normal weight 0.5 units/kg Overweight 0.6 units/kg Obese, insulin resistant, glucocorticoids Requires daily monitoring/adjustment Magaji V, et al. Clinical Diabetes 2011; 29(1):3-9. 15 16 Insulin Safety Considerations Hypoglycemia (BG 70mg/dL) Identify risk factors Prompt detection and treatment ADA 2017 clinically significant hypoglycemia < 54 mg/dl Severe associated with severe cognitive impairment regardless of level Nurse-driven protocol Should prompt dose adjustment <100 mg/dl TJC Glucometrics Moghissi ES, et al. Endocrine Practice 2009.; 15(4). RISK FACTORS OF HYPOGLYCEMIA Changes in nutrition/npo Changes in corticosteroids Sole use of sliding scale Lack of daily monitoring Kidney dysfunction Use of sulfonylureas β-blockers Inability to report symptoms Poor coordination of testing and admin. of insulin with meals Other Safety Considerations Transitions from IV to Subcutaneous insulin Give SQ basal insulin 2 hrs prior to stopping infusion Insulin Pens vs. Vials Prevent inadvertent sharing of pens risk of disease transmission Nursing double-check system Streamline insulin formulary to avoid multiple types/concentrations which can cause mix-ups (i.e. U-300, U-500, LASA*) Management strategies for planned and unplanned interruptions in nutrition Patient s Own Insulin Pumps Preventing readmissions Self-management education / survival skills Start insulin at discharge for admission A1C >9% *LASA Look alike sound alike 2017 ISMP Guidelines for Optimizing Safe Subcutaneous Insulin Use in Adults. 17 18 https://www.ismp.org/tools/guidelines/. Accessed 2017 May 18. 3
Concentrated Insulins Insulin Storage U-500-500 units/ml - 300 unit dose = 0.6 ml Humulin R Vials* Humulin R KwikPen U-300-300 units/ml - 300 unit dose = 1 ml dose Toujeo (glargine) SoloStar Pre-Filled Pen U-200-200 units/ml - 300 unit dose = 1.5 ml dose Humalog (lispro) KwikPen Tresiba (degludec) FlexTouch Pen May vary according to insulin type and presentation Do not freeze discard Vials/Pens Room Temp (opened or unopened): 28 days (BUD) Refrigerated unopened: until expiration date Pens: Do not refrigerate once in-use U-100-100 units/ml - 300 unit dose = 3 ml dose All others 2017 ISMP Guidelines for Optimizing Safe Subcutaneous Insulin Use in Adults. https://www.ismp.org/tools/guidelines/. Accessed 2017 May 18. 19 20 Managing Special Situations Enteral/Parenteral Feedings 1 unit insulin for every 10-15 g carbs (or ~50% of TDDI) Basal still important; a must for T1DM (insulin-dependent) Continuous enteral scheduled q4h if rapid or q6h if short acting If bolus feeds prior to feed TPN add to bag if >20 units of correctional in past 24 hrs (insulin-r) Glucocorticoid Therapy Perioperative Care Transitions of Care DKA Preventing admissions/readmissions Self-management education / survival skills Start insulin at discharge for admission A1C >9% FSHP Strategies for Hyperglycemic Management in the Inpatient Setting: Guidelines v Reality Jeffrey Ruff, PharmD 21 22 Buy-in and financial support from hospital administration is required for promoting a rational systems approach to inpatient glycemic management. Short-term increase in cost: o Increase in time for Physicians, Pharmacists, Nurses Long-term cost savings o Improved Clinical Outcomes, Decreased; LOS, Inpatient Complications, and Re-admissions Obstacles: Financial o Labor cost, drug cost Staffing o Physician, Pharmacist, Nursing Resistance o Physician, Pharmacy, Nursing staff Education o Lack of understanding Adverse Drug Events o Hypoglycemia Pract. 2009;15(No. 4) 23 Pract. 2009;15(No. 4) 24 4
Treatment strategies Inpatient Considerations o Severity of illness o Medications Corticosteroids o Nutritional Status Enteral/Parenteral Inconsistent dietary intake o Type and treatment of diabetes present o Hyperglycemia without diabetes Treatment strategies Oral v Parenteral o Discontinue oral upon admission o Initiate insulin Basal-Bolus Basal-Bolus Correctional Preferred Sliding scale Should not be used as single treatment strategy Hyperglycemic management in the hospital setting. Hassan, E. Am J Health-Syst Pharm. 2007; 64:S9-14 25 Pract. 2009;15(No. 4) 26 Implementation: Financial justification o Cost avoidance Decreased rate of infection Decreased Length of Stay Improved Outcomes o Bill for clinical diabetes management Accurate documentation and coding of unrecognized or uncontrolled diabetes, and diabetes complications. Implementation: Establish: o Hospital Protocols/Standing Orders o Owners Individual Physician, Pharmacist, Nursing Team approach Utilization of all members of healthcare team o Safety High Alert Medication Serious consequences of hypoglycemia Pract. 2009;15(No. 4) Hospital protocols for targeted glycemic control: Development, implementation, and Enhancing insulin-use safety in hospitals: Practical recommendations from an ASHP models for cost justification. Magee, M. Am J Health-Syst Pharm. 2007; 64:S15-20 Foundation expert consensus panel. Cobaugh, D., et al. Am J Health-Syst Pharm. 2013; 27 28 70:1404-13 Tools o Standing Orders Provides guidance Assist practitioners to meet guidelines Protocols built in Streamlines process Increased safety Eliminates Free Text Enhancing insulin-use safety in hospitals: Practical recommendations from an ASHP Foundation expert consensus panel. Cobaugh, D., et al. Am J Health-Syst Pharm. 2013; 70:1404-13 Parrish Medical Center: Basal/Bolus Order Set; Ruff, Swanson 2013 29 30 5
31 32 33 34 If pt has been on insulin prior to admission: Consider pts previous control (Hemoglobin A1c will be helpful) and increase dose as needed for stress/infection, decrease dose as needed for decreased intake American Diabetes Association Goals For non-critically ill medical and surgical patients: pre-meal = 100-140 mg/dl, all values < 180 mg/dl Anticipate changes: Status: severity of illness, surgery, stressors, ischemia, pre- and post-delivery Change in kidney, liver, cardiac function: SCr, electrolytes, urine output, fluid status Medications: changes in steroid dose, pressors, oral diabetic medications held or restarted Nutrition: changing oral intake, change in rates of D5W, TPN, tube feeds Who? Team o Physician, Nurse, Pharmacist o Each have role in implementing guidelines and patient care 35 36 6
Roles: Physician o Initiation of Standing Order Nurse o Monitor BG, Coordinate Meals. Pharmacist led Multiple Variations o Diabetes Management Team (DMT) o Inpatient blood glucose monitoring o Pharmacist-managed glucose collaborative practice agreement Pharmacist o Ongoing monitoring and dose adjustments Implementation of a pharmacist-led,multidisciplinary diabetes management team. Warrington, L. et al. Am J Health-Syst Pharm. 2012; 69:1240-5 Frontline Pharmacist Implementation of inpatient blood glucose monitoring by clinical pharmacists. Chapman, J. et al. Am J Health-Syst Pharm. 2013; 70:1480-81 Outcomes of a pharmacist-managed glucose collaborative practice agreement. Pugazhenthi, V. et al. Am J Health-Syst Pharm. 2016; 73(suppl 6):S148-54 37 38 What to do? Implementation a must o Improves outcomes and saves money Tailor approach to health system and available resources Use of Standing Orders and attached critical protocols Question and Answer Session AACE/ADA Consensus Statement on Inpatient Glycemic Control. Moghissi, ES et al. Endocr Pract. 2009;15(No. 4) 39 40 7