Intensive Management of Inpatient Hyperglycemia Nicole L. Artz, MD “The conventional view serves to protect us from the painful job of thinking.” John Kenneth Galbraith (1908-2006)

Outline Background Data Insulins Protocols Cases

Hyperglycemia – Scenarios Patient with known diabetes defined as FBG > 126 mg/dl or random BG >= 200 on 2 or more occasions. Patient with previously undiagnosed diabetes HgbA1C abnormal and/or hyperglycemia persists after hospital discharge. Stress hyperglycemia

Background Prevalence of DM in hospitalized patients- 12-26% Prevalence of inpatient hyperglycemia- 38% (chart review of 1886 medical and surgical pts at community teaching hospital) 1/3 with newly discovered hyperglycemia References: Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-91. Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87(3):978-82.

Background Why do we care about inpatient hyperglycemia?

Total In-patient Mortality Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87(3):978-82.

Additional studies correlating hyperglycemia with morbidity/mortality…. Acute MI- Increased risk of CHF, cardiogenic shock, and mortality… Cardiac Surgery- Greater mortality, increased deep-sternal wound infections, and more overall infections.. Acute CVA- Increased risk of mortality, poor functional recovery, and increased final infarct size… Elective Surgery- Increased risk of nosocomial infection w/ early postoperative hyperglycemia Capes SE, Lancet. 2000;355(9206):773-8. Capes SE, Stroke. 2001;32(10):2426-32. Parsons MW, Ann Neurol. 2002;52(1):20-8. Furnary, AP Circulation. 1999/100(#18)I-591. Pomposelli, JJ et al. J of Parenteral and Enteral Nurtrition, 1997: 22(2) 77-81.

Cause or Effect? Intervention Studies

Post-CABG Patients Portland Protocol Study On-going,17 year pre-post intervention study comparing conventional treatment with subcutaneous insulin (1987-1991) vs. continuous insulin infusion (1992-2001) in patients with diabetes. CII therapy normalized the rates of hospital mortality (2.5%) and DSWI rates (0.8%) in pts with DM to those of nondiabetic patients. Furnary, et al. J Thoracic Cardiovascular Surgery 125: 1007-1021, 2003

Average postoperative glucose (mg/dl) 14.5% Mortality 6.0% 4.1% 2.3% 1.3% 0.9% Average postoperative glucose (mg/dl)

Effect on Healthcare Resources… Length of Stay 3-BG (3 day average post-op BG) independently predictive of longer LOS: 1 day increased LOS for each 50 mg/dL increase in 3-BG. Cost of Care Conservatively estimated savings of $680 per patient. Furnary, et al. J Thoracic Cardiovascular Surgery 125: 1007-1021, 2003

SICU patients Randomized controlled trial of intensive insulin infusion therapy to maintain BG 80-110 mg/dl vs conventional therapy to maintain BG 180-200 mg/dl in mechanically ventilated surgical ICU pts. 60% were cardiac surgery patients. Van den Berghe G, et al. N Engl J Med. 2001;345(19):1359-67.

Mortality ARR-3.4% ARR-3.7% Intensive therapy also reduced episodes of bacteremia, acute renal failure requiring dialysis, # of blood transfusions, and critical illness polyneuropathy. Reduced ICU length of stay by 3 days for pts requiring >5 days of ICU care.

NO to Sliding Scales!! WHY? Sliding scale regimen ordered on admission is usually used throughout the hospital stay without modification Ineffective- Treats hyperglycemia after it has already occurred, instead of preventing the occurrence of hyperglycemia This “reactive” approach can lead to rapid changes in blood glucose levels, exacerbating both hyperglycemia and hypoglycemia Queale, W. Arch Intern Med/Vol 157, Mar 10, 1997, 545-552. Smith, WD, Am J Health Syst Pharm. 2005 Apr 1; 62(7): 714-9. Schoeffler JM, Ann Pharmacother. 2005 Oct; 39(10) 1606-9.

Basal/Bolus Concept In healthy patients, pancreas secretes large amounts of insulin with meals (“bolus or prandial”) However, it also makes smaller amount of insulin in between meals (when fasting, overnight, etc) to suppress liver glucose production (“basal”) We try to mimic this as much as possible with current therapy

Physiological Serum Insulin Secretion Profile Breakfast Lunch Dinner 50 Plasma insulin (µU/ml) 25 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time

The Basal/Bolus Insulin Concept Basal insulin Suppresses glucose production between meals and overnight 40% to 50% of daily needs Bolus insulin (prandial/mealtime) Limits hyperglycemia after meals Immediate rise and sharp peak at 1 hour 10% to 20% of total daily insulin requirement at each meal

Pharmacokinetics of Current Insulin Preparations Effective Onset Peak Duration Lispro/Aspart <15 min 1 hr 3 hr Regular 1/2-1 hr 2-3 hr 3-6 hr NPH/Lente 2-4 hr 7-8 hr 10-12 hr Glargine 1-2 hr Flat/Predictable 24 hr

Short-Acting Insulin Analogs Aspart Lispro 400 500 450 350 400 300 350 250 300 Plasma insulin (pmol/L) 200 Plasma insulin (pmol/L) 250 150 200 150 100 Regular 100 50 Regular 50 30 60 90 120 150 180 210 240 50 100 150 200 250 300 Time (min) Time (min) Meal SC injection Meal SC injection Heinemann, et al. Diabet Med. 1996;13:625–629; Mudaliar, et al. Diabetes Care. 1999;22:1501–1506.

Glargine vs NPH Insulin 6 NPH 5 Glargine 4 NPH Glucose utilization rate (mg/kg/h) 3 2 Glargine 1 10 20 30 Time (h) after SC injection End of observation period Lepore, et al. Diabetes. 1999;48(suppl 1):A97.

Basal/Bolus Treatment with Rapid-acting & Long-acting Insulin Analogs Breakfast Lunch Dinner Lispro Lispro Lispro Plasma insulin Glargine 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time

Insulin Requirements Basal Insulin Prandial Insulin Baseline insulin needed whether eating or NPO ex. Glargine (Lantus®) Prandial Insulin Also referred to as bolus or mealtime insulin, usually administered before eating ex. Lispro (Humalog®) and Aspart (Novolog®) Correction or Supplemental Insulin Insulin used to treat hyperglycemia that occurs before meals or between meals Given in addition to scheduled insulin At bedtime, often is given at a reduced dose in order to avoid nocturnal hypoglycemia With NPO patients or patient who is receiving scheduled nutritional and basal insulin but not eating meals

Initial Approach…. Check HgbA1C Accuchecks QAC and HS Discontinue Oral Diabetes Medications Cannot gain rapid control of hyperglycemia Sulfonylureas- Increased risk of hypoglycemia w/ decrease in po intake Metformin- Increased risk of lactic acidosis if ARF Thiazolidinediones- may be contraindicated by development of chf, edema

Calculating Basal/Bolus Insulin Type 2 DM on insulin- Add all insulin doses together (this is the Total Daily Dose) Type 2 DM new to insulin OR Newly Discovered Hyperglycemia- Calculate starting Total Daily Dose of 0.6 units/kg/day. In general, 50% of the total insulin should be basal and 50% mealtime insulin, the latter divided in 3 doses for each meal

BASAL Insulin Cut the TDD in half and give as insulin Glargine (Lantus®). This is Basal insulin. May give insulin Glargine (Lantus®) at any time and then re-dose every 24 hours.

PRANDIAL Insulin When the patient is eating, give the remaining 50% of the TDD as rapid acting insulin lispro (Humalog). Give 1/3 AFTER each meal. This is prandial insulin Cut the prandial dose in ½ if the patient only eats ½ the meal. Hold prandial dose if patient does not eat.

Correction Factor Insulin…the new, improved “sliding scale” To correct pre-meal hyperglycemia Given in addition to scheduled mealtime insulin as one injection after the meal Give if pt NPO Algorithms based upon the total insulin dose per day

Correction Factor Insulin Premeal BG Lispro Insulin 130-170 1 unit 171-220 2 units 221-270 3 units 271-320 4 units >320 5 units Premeal BG Lispro Insulin 130-170 1 unit 171-220 3 units 221-270 5 units 271-320 7 units >320 9 units 40 units insulin/day 41-80 units insulin/day

Correction Factor Insulin Premeal BG Lispro Insulin 130-170 3 unit 171-220 5 units 221-270 7 units 271-320 9 units >320 11 units >80 units insulin/day

Correction Factor Insulin Only HALF correction dose is given at bedtime

Goals for Ward Patients Pre-prandial BS 90-130 mg/dL All BS <180 mg/dl

Adjusting Basal Insulin Fasting BG Change to Glargine <70 ↓ 20% 71-90 ↓10% 90-130 no change 131-180 ↑ by 10% 181-230 ↑ 20% 231-280 ↑ 30% >281 ↑ 40% Make daily adjustments of basal insulin based on fasting (AM) BG

Adjusting Prandial Insulin Recalculate prandial insulin dose using new basal insulin amount divided by 3

If the Patient is NPO or unable to eat Insulin glargine (Lantus) should still be given Accuchecks every 6 hours Prandial insulin not needed Correction insulin should still be given BG goal 90-130 mg/dl

Patients without History of Diabetes In patients without a history of diabetes and normal hemoglobin A1C insulin glargine dose can be TAPERED by 20% of the first dose per day and they can be discharged without treatment

Transition from Drip to SQ Insulin Patient should be stable on the same IV drip rate for 3 hours Multiply the drip rate/hour X 20  Give this as daily dose of Glargine (Lantus®) SQ Discontinue the IV drip 2 hours after the insulin Glargine (Lantus®) dose May give insulin Glargine (Lantus®) at any time and then re-dose every 24 hours This is Basal insulin

Transition from Drip to SQ Insulin When patient is able to eat Insulin drip stable at a rate of 3 units/hour Glargine calculated as 3 X 20 = 60 units Glargine 60 units SQ given and drip stopped 2 hours later Patient to start eating Total lispro dose to be 60 units per day so 60/3  20 units with each meal

If the Patient is on Tube Feeds Consult Endocrine. If continuous, ALL insulin requirements should be supplied by Glargine. If suddenly stopped, immediately begin infusion of D10 at same rate tube feeds were running to avoid hypoglycemia.

If the Patient is on Steroids Consult Endocrine Increased post-prandial hyperglycemia- may need to use much greater prandial insulin doses, or change to NPH.

Discharge Patient with Type 2 Diabetes HbA1C >7% represents suboptimal diabetic control and anti-diabetic Rx should be improved prior to discharge. Each oral diabetic agent will only lower HbA1C by 1-2%. A pt w/ HbA1C of 12% on 2 oral agents will require insulin to reach goal <7%. Note: Illinois public aid now covers Lispro (Humalog) and Glargine (Lantus) for outpaients.

Practice Cases 45 yr old woman with h/o DM type 2 admitted for elective cholecystectomy. At home, taking glipizide 10 mg bid and Metformin 1000 mg po bid. Weight is 100 kg.

Case 1 Cont… What is her Total Daily Insulin Requirement? 100 kg X 0.6 units/kg = 60 units How much basal insulin (Lantus) should you give? 30 units (50% of TDD) How much prandial insulin will she need with each meal? 10 units given AFTER each meal.

Case 1 Cont… Which correction factor algorithm will she require? Medium Dose Algorithm Premeal BG Lispro Insulin 130-170 1 unit 171-220 3 units 221-270 5 units 271-320 7 units >320 9 units 41-80 units insulin/day

Case 1 Cont…. Post-operative Day 1 her fasting blood glucose is 170. Calculate her new basal and bolus insulin doses. Lantus 33 units Q 24 hours. Lispro 11 units after each meal.

Case 1 Cont… She does well and is ready for discharge on POD #3 Her HbA1C ordered at admission was 10%. She states that she takes her pills consistently at home. Discharge regimen?

Case 1 Cont… What additional things must happen before discharge? Patient diabetes education- DVD, patient handouts Ability to use glucometer appropriately Ability to give insulin injections Scripts for test strips, lancets, insulin, needles, and syringes!) Ensure f/u apt with PCP w/in 2 weeks

Case 2 58 y/o male with h/o DM type 2 previously treated with oral diabetes medications now admitted to D6 ICU after CABG. Started on insulin infusion per RN-initiated protocol. Determined ready for transfer out of the ICU to the floor on POD 2.

Case 2 The pt is on an insulin gtt at 3 units/hr. The nurse asks you for transfer insulin orders. What do you need to know to write these? Has the pt been on a stable drip rate for the last 3 hrs? Is the patient eating, or NPO?

Case 2 The nurse reports the insulin gtt has been stable at 3 units/hr for the past 3 hrs and the patient’s most recent BG was 116. Calculate the initial dose of insulin glargine. 3 X 20 = 60 units glargine When will you discontinue the insulin gtt? 2 hours after glargine is given

Case 2 Order prandial insulin for this patient. Lispro 20 units SQ given after each meal Order a correction factor insulin- which algorithm will you choose? High Dose Algorithm (>80 units insulin/day)

Case 2 You are called by the patient’s nurse. The patient’s pre-meal glucose was 140 but the patient did not eat his lunch. She is not sure how much insulin to give. What should you tell her? Hold the prandial insulin but give the correction factor insulin

Case 2 The following day, the patient’s fasting BG is 88. How will you adjust his insulin? Adjust basal insulin Decrease glargine (Lantus®) by 10%: 54 units SC glargine daily Adjust prandial insulin 54 units/3 = 18 units lispro (Humalog®) SC after each meal

Case 2 You follow the protocol, adjusting insulin doses daily until the patient is ready for discharge. Hgb A1C checked at time of admission was 10%. Current insulin regimen is: Glargine (Lantus®) 40 units daily Lispro (Humalog®) 13 units tid after meals

Case 2 Should this patient go home on insulin? Yes! (HgbA1C of 10%) Patient has Medicaid insurance. What insulin will you send him home on? Glargine (Lantus) and Lispro (Humalog) now covered!

Case 3 57 year old diabetic woman POD #4 who has been transitioned to SQ insulin 2 days ago but is still not eating. FBG this AM was 220. Current glargine dose is 20 units per day and lispro correction factor at low dose algorithm.

Case 3 Correction dose lispro of 2 units given now. The nurse wants to hold the glargine b/c the patient is not eating. What should you tell her? Give the Glargine! How much? Increase daily glargine dose by 20% so by 4 units  24 units glargine daily. The patient starts eating the next day. What dose of lispro should you order?

Case 3 Glargine dose is 24 units daily so total daily lispro dose will also be 24  24 units/3  lispro 8 units after each meal Next day, you are called because the patient’s BG at lunch is 65. She is awake and not symptomatic. How do you treat this?

Give 30 grams of carbohydrate Give 15 grams of carbohydrate To Treat HYPOGLYCEMIA ( Blood Glucose Less than 70 mg/dl ) If Patient is: Blood Glucose Treatment: ALERT & EATING BG is less than 50 mg/dl Give 30 grams of carbohydrate   ( 8 oz. of juice) BG = 50 - 69 mg/dl Give 15 grams of carbohydrate ( 4 oz. of juice ) NPO or NOT ALERT BG less than 70 mg/dl Give 25 grams (1 amp) D50 W IVP Notify MD!

Case 4 64 year old male who has no known history of diabetes and hemoglobin A1C of 5.4%. Transferred from the ICU on glargine 15 units per day. He will start eating today. How much lispro will you start?

Case # 3 Total daily lispro dose should be 15 units. Divided by 3 for dose of 5 units lispro with each meal. On the next day, insulin dose should be decreased by 20% glargine 12 units q day lispro 4 units with meals

Change has a considerable psychological impact on the human mind Change has a considerable psychological impact on the human mind. To the fearful it is threatening because it means things may get worse. To the hopeful it is encouraging because things may get better. To the confident it is inspiring because the challenge exists to make things better. King Whitney Jr.