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Hyperglycemic Control in Hospitalized Patients: Best Practice Susan S. Braithwaite Clinical Professor of Medicine University of North Carolina Glycemic Control Resource Room November 5, 2006 Objectives – to discuss: • Relationships of medical outcomes and cost to presence of diabetes, glycemic control, and / or treatment modality • Target range glucose • Intravenous infusion of insulin • Subcutaneous insulin (scheduled and correction therapy) • Prevention of hospital hypoglycemia • Diabetes patient self-management • Moving toward discharge • Managing complexity – orders sets completed by checking off boxes and filling in numbers, protocols activated by a single signature, and computerization Background Observational studies and comparisons of intensified regimens against historical controls show correlation between glycemic control and outcomes • Stagnaro-Green. Mortality in hospitalized patients with hypoglycemia and severe hyperglycemia. Mt. Sinai J Med 1995; 62: 422. • Umperriez. Hyperglycemia: an independent marker of inhospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002; 897: 978-82, 2002. • Finney. Glucose control and mortality in critically ill patients. JAMA 2003; 290: 2041. • Krinsley. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 2004; 79: 992-1000. • Pittas. Insulin Therapy for Critically Ill Hospitalized Patients: A Meta-analysis of Randomized Controlled Trials. Arch Int Med 1004; 164: 2005. • Capes. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001; 32: 2426. • Bruno. Admission glucose level and clinical outcomes in the NINDS rt-PA stroke trial. Neurology 2002; 59: 669. • Gentile. Blood glucose control after actue stroke: a retrospective study. Academic Emergency Medicine 2003; 10: 432. • Baird. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke 2003; 34: 2208. • Leigh. Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy. Stroke 2004; 35: 1903. • Lindsberg. Hyperglycemia in acute stroke. Stroke 2004; 35: 1903. • Gentile. Decreased mortality by normalizing blood glucose after acute ischemic stroke. Academic Emergency Medicine 2006. • Laird. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma 2004; 56: 1058. • Thomas. Early perioperative hyperglycaemia and renal allograft rejection in patients without diabetes. BMC Nephrology 2000;1:1. • Thomas. Early peri-operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study. Transplantation 2001;72:1321. • Melin. Protective effect of insulin on ischemic renal injury in diabetes mellitus. Kidney International 2002;61:1383. • Weiser. Relation between the duration of remission and hyperglycemia in induction chemotherapy for acute lymphocytic leukemia... Cancer 2004;100:1179-85. • Capes. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 355:773-8, 2000 • Foo. A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes. Heart 2003; 89: 512. • Schnell. Intensification of therapeutic approaches reduces mortality in diabetic patients with acute myocardial infarction: the Munich registry. Diabetes Care 2004; 27: 455. • Stranders. Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus. Arch Intern Med 2004; 164: 982. • Meier. Plasma glucose at hospital admission and previous metabolic control determine myocardial infarct size and survival in patients with and without type 2 diabetes. (LAMBDA study). Diabetes Care 2005;28:2551-2553. • Cheung. The hyperglycemia:intensive insulin infusion in infarction (HI5) study: a randomized controlled trial of insulin infusion therapy for myocardial infarction. Diabetes Care 29:2006;765. • Goyal. Prognostic significance of the change in glucose level in the first 24h after acute myocardial infarction: results from the CARDINAL study. European Heart Journal 2006;27:1289-1297. • Barsheshet. Admission blood glucose level and mortality among hospitalized nondiabetic patients with heart failure. Arch Intern Med 2006;166:1613-1619. • Chu. Early predictors of in-hospital death in infective endocarditis. Circulation 2004; 109: 1745. • Thomsen. Diabetes and outcome of community-acquired pneumococcal bacteriemia. Diabetes Care 2004;27: 70. • Falguera. Etiology and outcome of community-acquired pneumonia in patients with diabetes mellitus. Chest 2005; 128: 3233. • Pomposelli. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. J Parenteral and Enteral Nutrition; 1998; 22: 77. • Golden. Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes. Diabetes Care 1999; 22: 1408. • Latham. The association of diabetes and glucose control with surgical- site infections among cardiothoracic surgery patients. Infection Control & Hospital Epidemiology. 2001;10:607. • Vriesendorp. Early post-operative glucose levels are an independent risk factor for infection after peripheral vascular surgery. A retrospective study. Eur J Vasc Endovasc Surg 2004;5 : 520 • Szabo. Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting. Annals of Thoracic Surgery 2002; 74: 712. • Estrada. Outcomes and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting. Ann Thorac Surg 2003; 75: 1392-99. • McAlister. Diabetes and coronary artery bypass surgery: an examination of perioperative glycemic control and outcomes. Diabetes Care 2003; 26: 1518. • Gandhi. Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients. Mayo Clin Proc 2005; 80:862-866. • Furnary. Clinical effects of hyperglycemia in the cardiac surgery population: the Portland Diabetic Project. Endocrine Practice 2006;12(suppl 3): 22-26. • American Diabetes Association. Economic costs of diabetes in the U.S. in 2002. Diabetes Care 2003; 26: 917-932. • Ahmann A. Reduction of hospital costs and length of stay by good control of blood glucose levels. Endocrine Practice 2004; 10 (suppl 2): 53-56. • Vora. Improved perioperative glycemic control by continuous insulin infusion under supervision of an endocrinologist does not increase costs in patients with diabetes. Endocrine Practice 2004; 2: 112-118. • Almbrand B. Cost- effectiveness of intense insulin treatment after acute myocardial infarction in patients with diabetes mellitus: results from the DIGAMI study. Eur Heart J 2000; 21: 733-739. Background Heart surgery Portland: Deep sternal wound infection rate correlates with quartile of blood glucose on postoperative day 1 Zerr. Ann Thorac Surg 1997;63:356-61. Percent of patients on POD 1 with mean BG < 200 mg/dL was increased by using insulin infusion after cardiac surgical procedures 1499 in study group 968 historical controls Furnary Ann Thorac Surg 1999;67:352-62. Blood glucose differed among patients having deep sternal wound infections vs patients having no deep sternal wound infections after cardiac surgical procedures Furnary Ann Thorac Surg 1999;67:352-62. Over time, average postoperative glucose has continued to decline among patients undergoing heart surgery Furnary 2006 BG Introduce Portland Protocol Year Over time, mortality among patients with diabetes has decreased dramatically. Furnary 2006 At higher quintiles of blood glucose, the increase in overall mortality among patients with diabetes was overwhelmingly accounted for by an increase in cardiac-related mortality. Furnary 2003 Cardiac related mortality Non-cardiac related mortality BG < 150 > 250 Myocardial infarction DIGAMI I Study: Mortality was reduced among suspected and known diabetes patients by intensive insulin after acute myocardial infarction (glucose-insulin infusion, followed by at least 3 months of SQ insulin) Malmberg. BMJ 1997;314:1512-15. Hyperglycemia predicts 30-d and 1-year mortality in elderly patients with myocardial infarction, particularly those without recognized diabetes Mortality at given BG level with no diabetes with diabetes with no diabetes with diabetes Direct comparison of risk-adjusted 30-day mortality (A) and 1-year mortality (B) in patients with and without recognized diabetes across range of glucose values Kosiborod, M. et al. Circulation 2005;111:3078-3086 In patients both with and without type 2 diabetes, hyperglycemia at the time of MI is associated with : reduced prospective survival nondiabetes in diabetes, higher A1C Causality cannot be inferred; the authors called for randomized trials at higher of tight control tertile of BG, higher CK Meier. LAMBDA study. Diabetes Care 2005;28:2551-2553. diabetes Surgical ICU Leuven, Belgium: Morning blood glucose was reduced by intensive treatment in Van den Berghe’s ICU trial of insulin infusion ( 13% had previous diabetes ) 200 173 Subgroup on insulin 150 153 All in treatment group 100 103 mg/dL 50 Conventional Intensive Van den Berghe. N Engl J Med 2001;345:1359- 67 Survival increased with intensive insulin therapy ( nondiabetic patients included ) targeting BG 80-110 mg/dL among patients who remained in ICU > 5 days Van den Berghe. N Engl J Med 2001;345:1359- 67 Complications correlated with average blood glucose Filled bars < 110 Shaded bars 110-150 Open bars > 150 mg/dL Van den Berghe, Crit Care Med 2003 Although the Van den Berghe study was not designed to determine the threshold above which mortality increases, mortality was higher at glucose 110-150, compared to glucose < 110 mg/dL. > 150 mg/dL 110-150 < 110 Van den Berghe, Crit Care Med 2003 Hartford: Nosocomial infections in SICU N. Grey. Endocrine Practice 2004 125 vs 179 = av BG ( mg/dL) IV device, blood stream, both, surgical site, UTI, nosocomial pneumonia General and Medical ICU Hospital mortality rate in critically ill patients vs mean BG 45 40 35 30 Mortality Rate (%) 25 20 15 10 5 0 80–99 100–119 120–139 140–159 160–179 180–199 200–249 250–299 > 300 Mean Glucose Value (mg/dL) Krinsley. Retrospective review of 1,826 consecutive intensive care unit patients at The Stamford Hospital, Connecticut. Mayo Clin Proc. 2003;78:1471–1478. Intensive management protocol, reducing mean BG from 152.3 to 130.7 mg/dL in medical-surgical adult ICU patients, reduced mortality Percent reductions were • glucose > 200 mg/dL 56.3 % • new renal insufficiency 75 % • RBC transfusions 18.7 % • mortality 29.3 % • length of ICU stay 10.8 % Krinsley. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79:992-1000. Average blood sugar depicted in critically ill surgical patients at Tufts-New England Medical Center in 1997, before implementation of successive protocols dedicated to aggressively treating hyperglycemia. By Spring of 2002, the mean glucose was < 130 mg/dL. Nasraway. Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 3, 2006 254-258 Hyperglycemia responded to aggressive institution of successive intensive insulin protocols from 1997 to 2002. By 2002, the desired endpoint of blood glucose < 130 mg/dL was achieved. During the same interval, patient mortality was observed to have significantly declined, in spite of increasing severity of illness. Nasraway. Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 3, 2006 254-258 Effect of Intensive Insulin Therapy on Morbidity in Medical ICU Van den Berghe, G. et al. N Engl J Med 2006;354:449-461 Kaplan-Meier Curves for In-Hospital Survival Van den Berghe, G. et al. N Engl J Med 2006;354:449-461 Implication: Hospitals should focus on prevention of hyperglycemia as an important patient safety factor Target range blood glucose (AACE 2004) • Preprandial < 110 mg / dL • Peak postprandial: < 180 mg / dL • Critically ill surgical patients: 80 -110 mg / dL The targets for critically ill patients were determined from the Leuven, Belgium study, in which whole blood glucose methodologies were used Target range blood glucose • Noncritically ill (ADA 2005) Premeal blood glucose as close to 90-130 mg/dL as possible (midpoint 110 mg/dL) Postprandial blood glucose < 180 mg/dL • Critically ill Blood glucose as close to 110 mg/dL as possible and generally < 180 mg/dL These patients generally will require IV insulin Can benefits of glycemic control be shown for diseases sometimes managed outside of the ICU, with subcutaneous therapy ? What specific outcomes might be improved ? For hypoglycemia vs. tight glycemic control, what is the risk - benefit analysis in the setting of the general hospital ward ? Stroke Maintaining near normal BG levels after stroke may improve outcome (n = 765 with ischemic stroke) Percent Mortality Percent mortality by 48-hr BG control among 561 patients with BG 130 or higher on admission Euglycemic (n=204) Hyperglycemic 25 < 130 20 15 60 10 40 5 20 0 0 130-180 >180 Gentile. Blood glucose control after acute stroke: a retrospective study. Academic Emergency Medicine 2003; 10: 432. Persistent poststroke hyperglycemia is independently associated with infarct expansion Baird. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke 2003; 34: 2208. Pneumococcal Sepsis With pneumococcal bacteremia, the 30- d mortality is higher in the presence of diabetes mortality diabetes no diabetes Thomsen. Diabetes and outcome of community-acquired pneumococcal bacteriemia. Diabetes Care 2004;27: 70. Kidney Transplant In 50 patients with diabetes undergoing their first cadaveric renal transplantation, poor perioperative glycemic control in the first 100 postoperative hours was associated with an increased incidence of acute rejection • With mean BG < 200 mg / dL, only 3 of 27 patients had rejection episodes ( 11% ) • With worse control, the majority had rejection episodes ( 58% ) Thomas. Early peri-operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study. Transplantation 2001;72:1321. Among patients with vs without subsequent rejection: mean perioperative glucose in 1st 100 hours differed BG 270 BG 180 these patients had subsequent acute rejection these patients did not 48 – 72h In the 50 patients with diabetes undergoing their first cadaveric renal transplantation, postoperative infection ( POI ) occurred in 35, or 70%, at a mean of 10.8 days after transplantation Every patient with mean BG > 202 mg / dL over 1st 100 h after surgery developed infection ( n = 23 ). BG values below are for postop day 1. • Without POI, mean glucose 167 mg/dL • With POI, mean glucose 248 mg/dL Thomas. Early peri-operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study. Transplantation 2001;72:1321. Acute Lymphocytic Leukemia Duration of complete remission / median survival were shorter among 103 hyperglycemic patients ( 37% ) with acute lymphocytic leukemia Weiser Hyperglycemia: ≥ 2 BG of ≥ 200 mg / dL w / 30 d of induction chemo complete remission : 24 vs 52 mo median survival : 29 vs 88 mo Sepsis or any complicated infection (sepsis, pneumonia, or fungal) appeared more often in the hyperglycemic patients with ALL 38.8 40 Percent Sepsis 30 25.1 20 10 16.5 8 Any complicated infection 0 Nonhyperglycemic Hyperglycemic Weiser. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer 2004; 110:1179. Nosocomial Infections Among 100 consecutive diabetic elective surgery patients, nosocomial infection rate within first 14 postoperative days (overall 25.8 %), correlated significantly with BG on postoperative day 1 (POD 1). 35 31.3 30 25 Percent 20 Developing Infection 15 ≤ 220 > 220 11.5 10 5 0 Preop POD1 POD2 Pomposelli. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. J Parenteral and Enteral Nutrition; 1998; 22: 77. Early hyperglycemia ≥ 200 mg/dL in trauma patients was associated with higher infection and mortality rates independent of injury characteristics 40 34 32 Percent 30 22 20 13 Nonhyperglycemic Hyperglycemic 10 0 Infection Mortality Laird. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma 2004; 56: 1058. Post- operative glucose levels in the first 48 hr were an independent risk factor for infection after peripheral vascular surgery postoperative infection rate BG > 151 mg/ dL BG < 103 Vriesendorp. Early post-operative glucose levels are an independent risk factor for infection after peripheral vascular surgery. A retrospective study. Eur J Vasc Endovasc Surg 2004;5 : 520 Overall Mortality Total inpatient mortality was highest with newly recognized hyperglycemia Umpierrez. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002; 897: 97882, 2002. Length of Stay and Cost Length of stay was highest with newly recognized hyperglycemia 10 9 8 6 Days 5.5 4 4.5 2 0 Normoglycemia Known Diabetes New Hyperglycemia Umpierrez. J Clin Endocrinol Metab 2002; 897: 978-82, 2002. Economic Costs of Diabetes in the US in 2002 Diabetes Care 2003; 26: 917 Per capita medical expenditures per year • Without diabetes: 2, 560 • With diabetes: $ 13, 243 Expenditures in diabetes: $ • Office visits 10.9 % • Nursing home care 15.1% • Inpatient days 43.9% Deciding on a Treatment Plan in the Hospital to Maintain Glucose in the Target Range Deciding whether to maintain the ambulatory treatment plan in the hospital Metformin? Probably contraindicated ! Stop metformin in the hospital Insulin: components of daily requirement defined physiologically Units Stress / Drugs IV's / TF's Prandial True Basal Other orals ? Normal oral intake, drugs not renally excreted, no contraindications ? May be OK to continue other oral agents Healthy Sick Sick / NPO The Pattern of Insulin Requirement during Normal Health, Meal Plan, and Activity is Not Necessarily Reproduced in the Hospital 8 12 6 10 Insulin Requirement Continuous D5, TPN, or tube feeds 6 am 12 pm 6 pm 12 am Insulin Requirement Overnight Enternal Feedings / Daytime “Grazing” 8 12 6 10 Insulin Requirement Transitional Meal Plan with “Grazing” 8 12 6 10 Insulin Requirement High a.m. dose corticosteroids 8 12 6 10 Scheduled subcutaneous insulin Which pattern of carbohydrate exposure describes the patient ? • Discrete meals • Negligible carbohydrate • Continuous carbohydrate exposure • Transitional meal plan / grazing • Daytime grazing / overnight enteral feedings Generalizations about subcutaneous insulin therapy in the hospital Subcutaneous insulin in the hospital has 3 components • basal • nutritional (or prandial) • correction therapy Additional directions are attached to specific scheduled insulin orders, or are specified under protocols • “do not withhold” basal insulin for type 1 diabetes • “hold” or “reduce” prandial insulin for poor oral intake • “hold” nutritional insulin for interruption of dextrose-containing fluids, enteral nutrition, or other exposure to carbohydrate • “hold” regular insulin or rapid acting analog for low BG Standardized order sets are completed with check- marks and numbers Subcutaneous scheduled daily insulin Check appropriate times or meal times to right, and fill in insulin doses below. Rapid-acting insulin analog Short-acting insulin Regular Intermediate-acting insulin NPH Long-acting insulin analog Other insulin: ______________________ 0600 1200 1800 2400 or or or or Lunch Supper Bedtime ________ units ________ units ________ units ________ units ________ units ________ units ________ units ________ units ________ units ________ units ________ units ________ units Breakfast ________ units ________ units ________ units ________ units ________ units ________ units Twilight of the “Sliding Scale,” and “Today’s Insulin” Dawning Relative risk of hyperglycemic episodes (BG >300 mg/dL) among 171 hospitalized diabetes patients was greatest with sliding scale, when comparing antihyperglycemic drug therapies to nontreatment Queale 1997 4 3 2 1 0 Scheduled insulin Conservative Aggressive sliding or oral agents sliding scale alone scale alone A1C monitoring and use of scheduled insulin improved as a result of housestaff education on scheduled insulin combined with prohibition of sliding scale A1C drawn 100 Percent of Patients 75 Scheduled insulin BID Sliding Scale Use: 100 % D50 needed 99 68 Sliding Scale Use: 0% 50 25 32 32 30 26 0 Historical Controls Intervention Group Baldwin. Eliminating inpatient sliding scale. Diabetes Care 2005;28:1008. BG control improved as a result of housestaff education on scheduled insulin combined with sliding scale prohibition for treatment of hyperglycemic patients 250 200 Mean Glucose mg / dL 200 ± 51 150 ± 37 150 100 50 0 Historical Controls Intervention Group Baldwin. Eliminating inpatient sliding scale. Diabetes Care 2005;28:1008. Correction Dose Algorithms Algorithm 1 Algorithm 2 Algorithm 3 Algorithm 4 Algorithm 5 Algorithm 6 Rapid-acting analog [ TDDI ≈ 24 ( < 28 ) units, or wt < 56 kg] Rapid-acting analog [ TDDI ≈ 30 (28–36) units, or wt 56–73.9 kg] Rapid-acting analog [ TDDI ≈ 45 ( 37–55) units, or wt 74–111.9 kg] Rapid-acting analog [ TDDI ≈ 72 (56 –90) units, or wt 112–181.9 kg] Rapid-acting analog [ TDDI ≈ 120 (91–144) units, or wt 182 kg] Rapid-acting analog [ TDDI ≈ 180 ( > 144 ) units] Regular insulin [ TDDI ≈ 20 ( < 23 ) units, or wt < 46 kg] Regular insulin [ TDDI ≈ 25 ( 23–30) units, or wt 46–61.9 kg] Regular insulin [ TDD I ≈ 37½ (31– 46) units, or wt 62–93.9 kg] Regular insulin [ TDDI ≈ 60 (47–75) units, or wt 94–151.9 kg] Regular insulin [ TDDI ≈ 100 ( 76 – 120) units, or wt 152 kg] Regular insulin [ TDDI ≈ 150 ( > 120) units] BG BG BG BG BG BG units units units units units units 150-224 1 150-209 1 150-189 1 150-199 2 150-209 4 150-199 5 225-299 2 210-269 2 190-229 2 200-249 4 210-269 8 200-249 10 300-374 3 270-329 3 230-269 3 250-299 6 270-329 12 250-299 15 375-449 4 330-389 4 270-309 4 300-349 8 330-389 16 450 5 390 5 310-349 5 350-399 10 350-389 6 400 12 390 7 390 20 300-349 20 350 25 Admitting a hyperglycemic patient who is eating Subcutaneous insulin therapy in the hospital for patients eating discrete meals Insulin therapy in normal health (%) Insulin release in normal physiology (%’s) Basal Prandial Basal Prandial Correction Consistent carbohydrate diet ; fixed prandial insulin doses Patients who are eating Glargine ( ~ 50 % ) Rapid- acting analog ( ~ 50 % ) Insulin requirement 8 12 6 10 Advanced carbohydrate counting Glargine Rapid- acting analog 8 12 6 8 12 6 10 Insulin by pump Rapid- acting analog 10 8 12 6 10 A preferred hospital regimen for use with a consistent carbohydrate diet Glargine Lispro / aspart / glulisine 8 12 6 ( ~ 50 % ) ( ~ 50 % ) 10 The patient who is eating and running high blood glucose ... • Use insulin analogs • Use basal – prandial – correction therapy • “Just say no” to sliding scale Insulin analogs are the preferred therapy for patients who are eating Rapid- acting analogs (aspart, lispro, glulisine) are best reserved for prandial and correction dose therapy (not basal), whereas long- acting analog therapy (glargine, detemir) is best reserved for basal coverage (not nutritional) A Bad Practice: 70/30 Insulin plus Sliding Scale Scheduled or routine Sliding Scale • BID, or • Q4HRS, or 0800 & 1700 0200, 0600, 1000, 1400, 1800, 2200 This means 8 shots daily. There is a risk of stacking, & BG tests fail to synchronize: 0200, 0600, 0800, 1000, 1400, 1700, 1800, 2200 Tease out the basal and prandial components for patients admitted on premixed insulins • meal omission is inevitable • premixeds won’t work • the argument for analogs is reduction of hypoglycemia Apportion or reapportion the insulin • About 50% basal • About 50% prandial “ Teasing out ” the basal and prandial components of insulin in type 2 diabetes for a patient admitted on premixed insulin • Suppose Robert normally takes 70 / 30 insulin, 60 units at breakfast and 30 units at supper He sometimes has fairly severe lows • A SQ regimen is needed to permit occasional meal omission Basal insulin in type 2 diabetes is 40- 50 % of the usual total daily dose A regimen of scheduled insulin might be: – glargine 36 units (“cut 50% if NPO”) qHS – aspart 12 units (“hold if NPO”) WMEALS – aspart 2 units prn BG 150 -199 WMEALS, HS, 0300 – aspart 4 units prn BG WMEALS, HS, 0300 >199 “ Teasing out ” and “locking in” the basal insulin component in type 1 diabetes Requirement for exogenous insulin during prolonged fasting may disappear in type 2 DM, but even during prolonged fasting it is absolute in type 1 DM requirement for exogenous basal insulin vs time fasting type 1 DM type 2 DM Corticosteroids High a.m. dose corticosteroids Insulin Requirement Solution a. NPH — R --- 8 12 6 Glargine during cortico steroids ( ~ 30 % ) Solution b. Rapid- acting analog 8 12 10 6 10 8 am 12 6 10 Solution c. NPH added for prednisone “on” days Rapid- acting analog NPH 8 12 Glargine 6 10 Procedures, brief NPO status, or anesthesia < 1hr Lispro, aspart or glulisine Procedures, anesthesia and surgery Glargine Established basal therapy with peakless long- acting insulin analog 8 am 12 6 10 Prolonged NPO status or anesthesia > 1hr Glargine Doses today’s yesterday’s Yesterday’s Glargine Dose 6 am 12 pm 6 pm 12 am Insulin drip 6 am 12 pm 6 pm 12 am Preoperative planning in the office .... For patients receiving insufficient prandial coverage, overdoses of long-acting analog (glargine or detemir) established as home therapy may spell hypoglycemia once the patient is in the hospital ... Glargine or detemir, given daily, playing catchup NPO status BG BG 8 12 6 10 pm 8 12 6 10 pm Glargine or determinr, overdosed to play catchup, plus sliding scale ! BG 8 12 6 10 pm During NPO status, among type 1 diabetes patients, a previously established glargine dose maintains normoglycemia Mucha, Diabetes Care: 2004 Control days Fasting days Requirement for exogenous insulin during prolonged fasting or calorie restriction shows variability in Type 2 DM type 2 DM patient A patient B Long -acting analog > 50% of total insulin? On the night preoperatively, cut long -acting analog dose to be no more than 50% of daily total insulin, and consider 10 -20% further reduction ambulatory plan glargine 72 units qHS metformin sulfonylureas the night preoperatively glargine 36 units Long -acting analog < 50% of total insulin? On the night preoperatively, no dose reduction ambulatory plan glargine 12 units qHS glulisine 6 units WMEALS the night preoperatively glargine 12 units Insulin by pump 8 12 6 10 A 35 year old woman with type 1 diabetes • She is having bariatric surgery • Normally she wears an insulin pump • She is in your office asking for preoperative advice For procedures or NPO status, pump patient can hold the prandial insulin but maintain true basal insulin Lispro or aspart 8 12 6 10 A caution on subcutaneous therapy Delayed response and late snowballing from repeated insulin doses may occur among patients with poor perfusion of subcutaneous sites, as with • hypoalbuminemia • edema • hypotension • pressors Intravenous Infusion of Insulin: the only insulin treatment strategy specifically developed for use in the hospital Indications for intravenous insulin infusion • Diabetic ketoacidosis • Non-ketotic hyperosmolar state • Critical care illness • Myocardial infarction or cardiogenic shock • Post- operative period following heart surgery • NPO status in type 1 diabetes • General pre-, intra- and post- operative care • Organ transplantation • Stroke (possibly) • Exacerbated hyperglycemia during high- dose glucocorticoid therapy • Dose-finding strategy, anticipatory to initiation or reinitiation of subcutaneous insulin in type 1 or type 2 diabetes • Labor and delivery • Any illness for which prompt glycemic control is important to recovery Intravenous Infusion of Insulin: a well- designed protocol damps the swings of BG BG levels with insulin drip with no protocol BG levels with insulin drip with good protocol Using an algorithm that considers BG, insulin rate, and velocity of change, Goldberg and colleagues safely approached target Goldberg et al. Diabetes Care 27: 461, 2004 The BG results compared favorably with those of historical controls Goldberg et al. Diabetes Care 27: 461, 2004 First 72 Hours of Insulin Infusion, 24 Patients, 27 Runs 350 point of care BG, mg / dL, mean and SD 300 70 insulin infusion rate, units / hr, mean and SD 60 insulin infusion rate, mean point of care BG, mean 250 50 200 40 150 30 100 20 50 10 0 0 0 6 12 18 24 30 36 42 48 54 60 66 72 hours of insulin infusion Braithwaite et al. Diabetes Technology and Therapeutics 2006; 8 (4):476 Intravenous Insulin Infusion Targeting BG 80-110 mg/dL Column 1 Column 2 Column 3 Column 4 Column 5 Column 6 BG units/h BG units/h BG units/h BG units/h BG units/h BG units/h < 70 0.05 < 70 0.05 < 70 0.05 < 70 0.05 < 70 0.05 70- 74 0.1 70- 74 0.1 70- 74 0.1 70- 74 0.1 70- 74 0.1 75- 79 0.1 75- 79 0.2 75- 79 0.2 75- 79 0.2 75- 79 0.2 80- 84 0.2 80- 84 0.2 80- 84 0.3 80- 84 0.3 80- 84 0.3 80- 84 0.3 85- 89 0.3 85- 89 0.4 85- 89 0.4 85- 89 0.5 85- 89 0.6 85- 89 0.6 90- 94 0.4 90- 94 0.6 90- 94 0.7 90- 94 0.8 90- 94 1.0 90- 94 1.2 95- 99 0.5 95- 99 0.8 95- 99 1.1 95- 99 1.4 95- 99 1.9 95- 99 2.3 100-104 0.7 100-104 1.3 100-104 1.8 100-104 2.4 100-104 3.3 100-104 4.3 105-109 1 105-109 2 105-109 3 105-109 4 105-109 6 105-109 8 110-127 1.2 110-121 2.3 110-122 3.5 110-127 5 110-122 7 110-127 10 128-144 1.5 122-133 2.6 123-134 4 128-144 6 123-134 8 128-144 12 145-162 1.7 134-144 3 135-147 4.5 145-179 8 135-159 10 145-162 14 163-179 2 145-162 3.5 148-159 5 180-214 10 160-184 12 163-179 16 180-249 3 163-179 4 160-209 7 215-249 12 185-209 14 180-214 20 250-319 4 180-249 6 210-259 9 250-319 16 210-259 18 215-249 24 320-389 5 250-319 8 390 320 6 10 260-309 11 310 13 320-389 20 390 24 260-309 22 310 26 250-319 32 320 40 Braithwaite et al. Diabetes Technology and Therapeutics 2006; 8 (4):476 Blood Glucose (BG) Distribution after First Reaching BG < 110 mg/dL , Analysis Shown Using BG or Patient Run as the Unit of Observation 23 patients, 1537 BG’s, 25 / 27 patient runs; % 50 2 patients did not reach BG < 110 before interruption of infusion 40 BG Patient Run 30 20 10 0 BG < 70 70 ≤ BG < 110 110 ≤ BG BG ≥ 140 < 140 in this series of 1537 BG measurements, among the 23 patients or 25 runs in which target BG < 110 was reached, there were 31 BG measurements < 70 mg/dL, and in this series none < 50 mg/dL. Prevalence of 60 ≤ BG < 70, 16 / 25 runs Prevalence of 50 ≤ BG < 60, 60 ≤ BG < 70 8 / 25 runs 50 ≤ BG < 60 Trauma Patient with Type 2 Diabetes, Tube Feeds at Target 450 70 insulin infusion rate point of care BG 400 60 capillary BG, 350 mg/dL, mean and SD insulin infusion, units / hr, mean and 50 SD Changing to higher column here alters assumed maintenance rate from 4 to 6 units per hour. 300 250 40 Changing to higher column here alters assumed maintenance rate from 6 to 8 units per hour. Changing to lower column here alters assumed maintenance rate from 8 to 6 units per hour. 200 30 150 20 100 10 50 0 0 0 6 12 18 24 30 36 42 hours of insulin infusion 48 54 60 66 72 Insulin to cover TPN • Distribution of insulin, desired – 67-80 % of the insulin in the TPN bag – 20 -33 % as correction therapy by SQ injection or IV infusion • Redistribution strategy – add 2 /3’s of yesterdays correction therapy to today’s bag Intravenous insulin infusion under basal conditions correlates well with subsequent subcutaneous insulin requirement Hawkins. Endocrine Practice: 1995 Total IV vs SQ 24h Insulin Requirements Units SQ Units IV Proposed predictors of successful transition from intravenous insulin to SQ insulin after CABG • Type 2 diabetes or nondiabetes ( hospital hyperglycemia ) • Uncomplicated CABG and / or valve surgery • Patient extubated, no pressor support, eating • Transfer orders written • Stable BG < 130 mg/dL • Insulin infusion ≤ 2 units / h overnight • Projected insulin dose 48 units / d Possible predictors of hyperglycemia after early transition to SQ insulin after heart surgery • Type 1 diabetes • COPD • Morbid obesity • Bilateral internal thoracic artery harvesting • Heart transplant • Ventilator dependency, pressor support, IABP, NPO status • Corticosteroids • No transfer orders written • Glucose > 130 mg / dL while on the insulin infusion • Infusion rate > 2 units / h overnight • Projected insulin dose > 48 units / d Transition off intravenous insulin infusion .... Constructing a profile for scheduled subcutaneous insulin …. Lispro / Aspart / Glulisine SQ Regular NPH Glargine 6 pm 12 am 6 am 12 pm The Time Arrives to Stop Insulin Drip Discrete meals? No NPH and regular insulin Yes Glargine and rapid-acting analog In the following case of a patient who is eating, if transfer orders are written .... what is needed for glycemic management ? Estimating initial SQ basal insulin from drip It is 8 am on the morning of postop day 3 after CABG. The patient is well, still on insulin drip. There were no overnight pressors or dextrose. Since yesterday, as prandial insulin, 4 units aspart are given with each meal. Based on the insulin requirement during 8 hr overnight, if nothing changes, what is the 24h basal requirement? • 12 -2 am 1.5 unit / hr • 2 -4 am 1.0 unit / hr • 4 -6 am 1.5 unit / hr • 6 -8 am 2.0 unit / hr Answer: • Average hourly insulin was 1.5 units / hr • 24 hr basal requirement is 36 units • Consider ~ 20 -33 % basal dose reduction each day during recovery • Adjust prandial doses upward each day • Eventual goal: 50% basal and 50% prandial The hyperglycemic patient receiving continuous exposure to carbohydrate, or no carbohydrate .... Insulin requirement during continuous D5, TPN or enteral feedings 8 12 6 10 Prolonged NPO Status Glargine (not more than basal) Regular (at least 50 %) ---- Regimens for patient while NPO, on IV’s, or receiving continuous enteral feedings 6 NPH 6 12 6 10 2 6 10 2 NPH q 6 hr (~ 67 %) — R --- q 6 hr (~ 33 %, hold if low) 12 6 12 6 12 Long- acting insulin doses should not exceed basal requirements during continuous enteral feedings Prescribe glargine Corpak falls out BG q 2 hr, dextrose if < 120 6 pm 12 am 6 am 12 pm Mixtures of NPH and regular insulin q 6 – 8 h maintain a flat- line, safe and rapidly reversible insulin effect for a patient while NPO, on IV’s, or receiving continuous enteral feedings — NPH q 6 hr (~ 67 %) R q 6 hr (~ 33 %, hold if low) 6 12 6 --- 12 In the following case of a patient not eating, if transfer orders are written... what is needed for glycemic management ? Estimating combined basal and nutritional coverage from drip A stable ventilator- dependent trauma patient has had a tracheostomy and PEG procedure. Over the past 24h he has received 72 units of insulin daily by intravenous infusion to cover enteral feedings, which have been at target for 24 hr. How might subcutaneous orders be written to permit transition off of the insulin infusion? One acceptable answer : • NPH 12 units q 6 h ( hold if tube feeds stop ) • Regular insulin 6 units subcutaneously q 6 h ( hold if tube feeds stop, hold if BG < 100 ) • Correction dose regular insulin “prn” – BG 150 - 199 + 2 units – BG 200 - 249 + 4 units – BG 250 or higher + 6 units • Stop insulin drip 2 h after first dose of subcutaneous insulin Grazing ( transitional meal plans, nutritional supplements ) .... Grazing Insulin Requirement Transitional Meal Plan with “Grazing” NPH and Regular Insulin Transitional Meal Plan with “Grazing” NPH — R --- 8 12 6 10 8 am 12 6 10 Insulin regimen, no tube feeds, for patients attempting to eat ( transitional meal plan with “grazing”) • Estimate daily insulin requirement and split 2/ 3 in AM, 1/ 3 in PM • 2/ 3 of AM dose as NPH, 1/ 3 as regular • 1/ 2 of PM dose as regular at 1700 • 1/ 2 of PM dose as NPH at 2200 • Hold scheduled regular for BG < 90 Example of a “grazing” patient • A postoperative patient receives nutritional supplements between meals and grazes on trays • 36 units of insulin are required daily • Sample insulin orders: – NPH 16 units before breakfast – regular insulin SC 8 units before breakfast – regular insulin SC 6 units before supper – NPH 6 units qHS – regular insulin 2 units prn BG 150 -199 WMEALS, HS – regular insulin 4 units prn BG WMEALS, HS > 199 Overnight tube feeds .... Ovenight enteral feedings / daytime grazing Insulin Requirement NPH and Regular Insulin NPH — R --- 8 12 6 10 8 am 12 6 12 70 / 30 change dose change frequency to “QPM enter additional directions free text pre- med for TF’s, hold if no TF’s select " pre- med" for priority Today’s Insulin Dose How much? • How much to start with? • How much for today? Initial insulin calculation, hospitalized patient, type 2 diabetes No clue where to start ? start low.... • basal insulin requirement 0.15 units /k • basal + prandial insulin 0.3 units /k if eating Known preadmission TDDI (total daily dose of insulin) ? • basal insulin requirement if no longer eating 20 - 25 % of preadmission TDDI During continuous nutritional support or IV dextrose infusion, • provide basal insulin 0.15 units per kilo • provide nutritional insulin, initially estimated as 1 unit per 10 gm carbohydrate • cover both needs continuously For type 2 diabetes -If insulin is required at all • the requirement for exogenous insulin may vanish during caloric restriction or development of organ dysfunction • calculations on a “per kilo” basis may overestimate basal needs when overnutrition ceases How much to start with ? • Melinda: weight 80 kilos • Problem: ovarian carcinoma, type 2 diabetes • Status: postop, NPO, D5 in 0.45 at 100 cc/hr • Basal insulin: ________ units per 24 hr • Insulin to cover D5: ________ units per 24 hr • Total insulin / 24 hr: ________ units per 24 hr Type 2 diabetes, NPO, continuous D 5 W • Melinda: weight 80 kilos • Status: postop, NPO, D5 in 0.45 at 100 cc/hr • Basal insulin: 12 units per 24 hr • Insulin to cover D5: 12 units per 24 hr • Total insulin / 24 hr: 24 units per 24 hr • SQ insulin orders: – 4 units NPH q 6h (hold if D5 stops ) – 2 units regular insulin q 6h (hold if D5 stops, hold if BG < 90 ) – Correction dose algorithm for highs Correction therapy signals the need for a change of scheduled therapy to prevent recurrent hyperglycemia It is common early in the admission to rely excessively on correction doses and to underestimate the need for scheduled insulin when using subcutaneous therapy Units Correction Scheduled Day 1 Day 3 Dose- finding strategy • Determine yesterday’s total insulin dose actually administered • Review yesterday’s glycemic control • Calculate today’s scheduled insulin dose (this example uses peak glucose targets appropriate during D5 or tube feeds) – some BG < 90 80 % of yesterday’s total – BG’s 100 % of yesterday’s total 90 - 179 – some BG ≥ 180, no BG < 90 110 % of yesterday’s total How much for today ? A patient on tube feeds received 6 units NPH and 3 units regular insulin as scheduled every 6 hr, total 36 units for the day, plus the following correction doses of regular insulin: 0600 BG 157 + 1 unit 1200 BG 207 + 2 units 1800 BG 199 + 2 unit 2400 BG 263 + 3 units Assuming nothing else has changed, what is today’s dose of scheduled insulin? A. 24 units B. 34 units C. 44 units D. 48 units Answer (doing it one doctor’s way): • Total dose given yesterday was 44 units • 110 % of yesterday’s dose is 48 units • Today’s insulin dose is 48 units, 8 N, 4 R at 0600, 1200, 1800, and 2400 Prevention of Hospital Hypoglycemia An analysis of proximate causes of hospital hypoglycemia suggests that iatrogenic hypoglycemia usually is predictable and preventable (Fischer): Decreased intake of calories Adjustment of insulin dosage Incorrect dose of insulin given No cause identified Insulin or secretogogue previously prescribed. Triggering Events for Hypoglycemia • Transportation off ward causing meal delay • New NPO status • Interruption of intravenous dextrose • Interruption of TPN • Interruption of enteral feedings • Interruption of continuous renal replacement rx Insulin previously prescribed. Triggering events for hypoglycemia ? Yes No Insulin given? Except for basal insulin in type 1 diabetes and correction doses: Hold insulin Yes Increase BG monitoring to q 2 hr for timeframe of action of the insulin, and: Give carbohydrate for BG < 120 mg/dL -oral, IV dextrose infusion, or, for volume restricted patients, concentrated dextrose Moving toward Discharge Was it just “hospital hyperglycemia?” • Review A1C from first day of admission – > 6.0 % ? – < 5.2% ? • Followup BG in outpatient setting Greci. Diabetes Care 2003 A1C- driven therapeutic modifications were followed by improvement of A1C ( 34 of 98 patients were evaluable after 12 mo ) Baldwin. Eliminating inpatient sliding scale. Diabetes Care 2005;28:1008. How will change be promoted ? Managing Complexity : Standardized Order Sets and Computerized Order Entry • Consistent carbohydrate meal plan • Intravenous infusion of insulin • Diabetes hospital patient self-management • Scheduled subcutaneous insulin • Oral antihyperglycemic agents • Combination insulin / oral antihyperglycemics • Point-of-care glucose monitoring • Correction dose insulin Standardized order sets can guide and teach Summary Summary • Hyperglycemia is a patient safety factor. • At the time of transition from intravenous insulin therapy, “scheduled” or “routine” or “programmed” subcutaneous insulin is the mainstay of glycemic management. • Good care involves discovery and ongoing revision of daily insulin dose, replacing “correction” therapy with “scheduled” subcutaneous insulin. • Hypoglycemia in the hospital is mostly preventable (by means other than undertreatment of diabetes). • Sliding scale is ineffective and dangerous and should be eliminated. • Patients conscious, eating, and experienced in self-management should continue self-management in the hospital. • Nation-wide opportunities for improvement include preadmission and preanesthetic planning, facilitation of insulin drip therapy, protocols for hypoglycemia prevention, standardization of diabetes order sets and correction dose algorithms, computerized order entry that guides and teaches, and enabling policies with safety provisions on patient self-management, patient education, and discharge planning.