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Management of Hyperglycemia and Diabetes in the Hospital: Case Studies. Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Atlanta, Georgia. Hyperglycemia in Hospitalized Patients. Hyperglycemia occurred in 38% of hospitalized patients 26% had known history of diabetes
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Managementof Hyperglycemia and Diabetes in the Hospital: Case Studies Bruce W. Bode, MD, FACE Atlanta Diabetes AssociatesAtlanta, Georgia
Hyperglycemia in Hospitalized Patients • Hyperglycemia occurred in 38% of hospitalized patients • 26% had known history of diabetes • 12% had no history of diabetes • Newly discovered hyperglycemia was associated with: • Longer hospital stays • Higher admission rates to intensive care units • Less chance to be discharged to home (required more transitional or nursing home care) Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978–982.
Hyperglycemia Is an Independent Marker of Inpatient Mortality in Patients With Undiagnosed Diabetes P < 0.01 P < 0.01 In-hospital Mortality Rate (%) Patients With Normoglycemia Patients With History of Diabetes Newly Discovered Hyperglycemia Adapted from Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978–982.
66% of AMI patients have IGT or previously undiagnosed T2DM on 75 g OGTT (35% IGT; 31% DM) Percentage of Population (n = 1181) Prevalence of Hyperglycemia in 181 Cardiac Patients Without Known Diabetes Norhammar A. Lancet. 2002;359:2140-2144.
Hospital Costs Account for Majority of Total Costs of Diabetes Per Capita Healthcare Expenditures (2002) Diabetes Without diabetes Hogan P, et al. Diabetes Care. 2003;26:917–932.
Case 1: Patient With an Acute MI • 53-year-old man with DM 2 on SU, metformin, and glitazone presents with an acute MI • BG random is 220 mg/dL • What do you recommend for glucose control? • Sliding-scale rapid analog? • Basal/bolus insulin therapy? • IV insulin drip?
Case 1: Patient With an Acute MI • What is your glycemic goal? • 80 to 110 mg/dL • 80 to 140 mg/dL • 80 to 180 mg/dL
Glycemic Threshold in Acute MI and Intervention (PTCA) • DIGAMI supports BG <180 mg/dL • Minimal other data: • PTCA reflow better with BG 159 than 209 mg/dL Malmberg K. BMJ. 1997;314:1512-1515. Iwakura K, et al. J Am Coll Cardiol. 2003;41:1-7.
DIGAMI Study:Diabetes, Insulin Glucose Infusion in Acute Myocardial Infarction (1997) • Acute MI with BG >200 mg/dL • Control vs Intensive Insulin Treatment • Intensive Insulin Treatment IV insulin for >24 hours followed by 4 insulin injections/day for >3 months Malmberg K, et al. BMJ. 1997;314:1512-1515.
Cardiovascular Risk:Mortality After MI Reduced by Insulin Therapy in the DIGAMI Study Standard treatment IV insulin 48 hours, then4 injections daily All Subjects Low-risk and Not Previously on Insulin .7 .7 (N=272) (N=620) .6 .6 Risk reduction (51%) Risk reduction (28%) .5 .5 P=0.011 P=0.0004 .4 .4 .3 .3 .2 .2 .1 .1 0 0 0 1 2 3 4 5 0 1 2 3 4 5 Years of Follow-up Years of Follow-up Malmberg K, et al. BMJ. 1997;314:1512-1515.
DIGAMI 2 Study • 48 hospitals in 6 countries • 3 groups: • Group 1: GIK for 24 hours followed by home insulin Rx (N = 474) • Group 2: GIK infusion followed by standard glucose control (N = 473) • Group 3: Routine metabolic management based on local practice (N = 306) Malmberg K et al DIGAMI 2. European Heart J 2005; 26 (650-61)
Conclusion • Overall mortality was lower than expected • Overall mortality similar to nondiabetic population • The 3 glucose management strategies did not result in differences of metabolic control • Target glucose levels not achieved in the intensively insulin treatment group
1977 Heng 8.3 0.0 0.6 0.2 1978 Stanley 7.3 16.4 -2.5 2.8 1983 Rogers 6.5 12.3 -1.9 2.4 1987 Satler 0.0 0.0 0.0 0.0 P = 0.007 1965 Mittra 11.8 28.3 -7.0 6.8 1967 Pilcher 13.9 29.3 -2.6 3.4 1968 Pentecost 15.0 16.0 -0.5 6.5 1968 MRC 21.4 23.6 -5.1 41.5 P = 0.07 1971 Hjermann 10.6 20.0 -4.8 6.8 P = 0.004 All Patients 16.1 21.0 -24.0 70.4 Overview of GIK Therapy for Acute MI: A 30year Perspective Odds Ratio and Cls Year Study Mortality Rate (%) GIK Better Placebo Better GIK Control O-E Variance 1 GIK = glucose–insulin–potassium; MI = myocardial infarction; CI = confidence interval. Fath-Ordoubadi F, Beatt KJ.Circulation. 1997;96:1152–1156. Reprinted with permission (http://lww.com)
CREATE-ECLA • Worldwide study with over 20,000 subjects with ST-elevation MI (STEMI) • GIK infusion vs Control • Outcome: 30 day CV events Mehta, S et al: JAMA 293: 437- 446, 2005
Baseline Glucose Associated with Mortality JAMA 293:437, 2005 % mortality Lowest Middle Highest Glucose Tertile
Case 1: Patient With an Acute MI • For acute MI with elevated glucose, you can either give: 1. IV insulin variable drip or 2. GIK in type 2’s who are easily controlled or 3. ? Intensive SC delivery
Case 1: Patient With an Acute MI Now Plans to Go for CABG • What is your glycemic goal? • 80 to 110 mg/dL • 80 to 140 mg/dL • 80 to 180 mg/dL
Mortality of DM Patients Undergoing CABG Furnary AP, et al. J Thorac Cardiovasc Surg. 2003;123:1007-1021.
Glycemic Threshold in CABG • Portland data suggest BG: • <150 mg/dL for mortality • <175 mg/dL for infection • <125 mg/dL for atrial fibrillation Furnary AP, et al. J Thorac Cardiovasc Surg. 2003;123:1007-1021.
Costs of Hyperglycemia in the Hospital For each 50 mg/dL rise in glucose: Length of Stay increases by 0.76 days Hospital Charges increase by $2824 Hospital Costs increase by $1769 Furnary et al Am Thorac Surg 2003;75:1392-9
Surgical ICU MortalityEffect of Average BG P=0.0009 BG>150 110<BG<150 P=0.026 BG<110 Van den Berghe G, et al. Crit Care Med. 2003;31:359-366.
Mortality Sepsis Dialysis Blood Transfusion Polyneuropathy Percent Reduction 34% 41% 44% 46% 50% Intensive Insulin Therapy in Critically Ill Patients—Morbidity and Mortality Benefits van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.
Target Blood Glucose • 80–110 mg/dL ICU patients • 80–140 mg/dL in other surgical and medical patients • 70–100 mg/dL in pregnancy
Threshold Blood Glucose for Starting IV Insulin Infusion • Perioperative care > 140 mg/dL • Surgical ICU care > 110-140 mg/dL* • Nonsurgical illness > 140-180 mg/dL† • Pregnancy > 100 mg/dL *Van den Berghe’s study supports 110 mg/dL; Finney’s study supports 145 mg/dL. †If drip indication is failure of SQ therapy, use 180 mg/dL; if indication is specific condition (DM 1/ NPO, MI, etc ), use 140 mg/dL.
The Ideal IV Insulin Protocol • Easily ordered (signature only) • Effective (gets to goal quickly) • Safe (minimal risk of hypoglycemia) • Easily implemented • Able to be used hospital-wide
Essentials of a Good IV Insulin Algorithm • Easily implemented by nursing staff • Dilution of insulin per hospital policy (0.5 or 1U/cc) • Able to seek BG range via: • Hourly BG monitoring • Adjusts to the insulin sensitivity of the patient • Contains transition orders to SC insulin when stable
Practical Closed Loop Insulin Delivery A System for the Maintenance of Overnight Euglycemia and the Calculation of Basal Insulin Requirements in Insulin-Dependent Diabetics 1/slope = Multiplier = 0.02 6 5 4 Insulin Rate (U/hr) 3 2 1 0 0 100 200 300 400 Glucose (mg/dL) White NH, et al. Ann Intern Med. 1982;97:210-214.
Continuous Variable Rate IV Insulin Drip • Starting rate units/hour = (BG – 60) x 0.02 where BG is current blood glucose and 0.02 is the multiplier • Check glucose every hour and adjust drip • Adjust multiplier to keep in desired glucose target range (80 to 110 mg/dL or 100 to 140 mg/dL)
Continuous Variable Rate IV Insulin Drip • Adjust multiplier (initially 0.02) to obtain glucose in target range 80 to 110 mg/dL • If BG >110 mg/dL and not decreased by 15%, increase by 0.01 • If BG <80 mg/dL, decrease by 0.01 • If BG 80 to 110 mg/dL, no change in multiplier • If BG is <80 mg/dL, give D50 cc = (100 – BG) x 0.4 • Give continuous rate of glucose in IVFs (do not feed meals on drip without bolus SC) • Once eating, continue drip till 2 hours post SQ insulin
Glucommander Average and Standard Deviation of of All Runs 1985 to 1998; 5808 runs, 120,618 BG’s Davidson et al, Diabetes Care 28(10): 2418-2423, 2005
Typical Glucommander Run Glucose Glucose Hi Low Multiplier Multiplier Insulin Insulin Hours Davidson et al, Diabetes Care 28(10): 2418-2423, 2005
Case 1: Patient With an Acute MI Now Post-CABG and Ready to Eat • Currently on IV insulin at ~2 units IV/hr • What do you now do? • Sliding scale rapid acting insulin only? • Basal/bolus insulin therapy? • Premixed insulin therapy? • Basal insulin?
Physiologic Serum Insulin Secretion Profile 75 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
Basal/Bolus Treatment Program With Rapid-acting and Long-acting Analogs 75 Breakfast Lunch Dinner Aspart, Lispro or Glulisine Aspart, Lispro, or Glulisine Aspart, Lispro, Or Glulisine 50 Plasma insulin (μU/mL) Glargine or Detemir 25 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time
Converting to SC Insulin • If >0.5 U/hr IV insulin required with normal BG, start long-acting insulin (glargine) • Must start SC insulin at least 2 hours before stopping IV insulin • Some centers start long-acting insulin on initiation of IV insulin or the night before stopping the drip
IV Insulin Infusion Under Basal Conditions Correlates Well With Subsequent SC Insulin Requirement Total Intravenous vs Subcutaneous 24-HourInsulin Requirements (units) Subcutaneous (units) Intravenous Units IV Hawkins JB Jr, et al. Endocr Pract. 1995;1:385-389.
Converting to SC Insulin • Establish 24-hour insulin requirement • Extrapolate from average over last 4-8 hours,if stable • Give half the amount as basal • Give PC boluses based on CHO intake • Start at CHO/ins 1 CHO = 1.5 units rapid-acting insulin • Monitor AC TID, HS, and 3 AM • Correction bolus for all BG >140 mg/dL • (Bg-100)/(1700/daily insulin requirement)
Case 2: A Person on steroids with new hyperglycemia (BG ~225 mg/dl) • What is the best insulin treatment for this patient on steroids? (BG 150 to 300 mg/dL) • Sliding scale only with rapid-acting insulin? • IV insulin variable rate infusion? • NPH or 70/30 twice a day? • Basal Insulin once a day? • Bolus insulin premeal? • Basal Bolus insulin therapy?
Basal/Bolus Treatment Program With Rapid-acting and Long-acting Analogs 75 Breakfast Lunch Dinner Aspart, Lispro or Glulisine Aspart, Lispro, or Glulisine Aspart, Lispro, Or Glulisine 50 Plasma insulin (μU/mL) Glargine or Detemir 25 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time
How to Initiate MDI • Starting dose = 0.5 x wt in kg • Basal dose (glargine) = 40% to 50% of starting dose given at bedtime or anytime • Bolus dose (aspart/lispro) = 15% to 20% of starting dose at each meal • Correction bolus = (BG - 100)/correction factor, where CF=1700/total daily dose
How to Initiate MDI • Starting dose = 0.5 x wt in kg • Weight is 100 kg; 0.5 x 100 = 50 units • Basal dose (glargine) = 50% of starting dose at HS; 0.5 x 50 = 25 units at HS • Total bolus dose (aspart / lispro) = 50% of starting dose ÷ 3; 0.5 x 50 = 25 ÷ 3 = 8 units AC (TID) • Correction bolus = (BG - 100)/ CF, where CF=1700/total daily dose; CF=30
250 – 10030 = 5.0 units Correction Bolus Formula Current BG - Ideal BG Glucose correction factor • Example: • Current BG: 250 mg/dL • Ideal BG: 100 mg/dL • Glucose correction factor: 30 mg/dL
Case 3: A Person With Diabetes on Tube Feedings • What is the best insulin treatment for a DM patient on tube feedings? (BG 150 to 300 mg/dL) • Sliding scale only with rapid-acting insulin? • IV insulin variable rate infusion? • NPH or 70/30 every 8 hours? • Glargine every 12 hours? • Regular insulin every 6 hours?
Case 3: A Person With Diabetes on Tube Feedings (cont’d) • What is the best insulin treatment for a DM patient on tube feedings? (BG 150 to 300 mg/dL) If unstable, first give IV insulin and determine the requirement over 24 hours and then change to SC basal (glargine q12h) with supplemental rapid-acting every 4 to 6 hours Can also use NPH q8h or regular q6h as the basal dose
Case 4: A Person With Diabetes on TPN • What is the best insulin treatment for a DM patient on TPN? (BG 150 to 300 mg/dL) If unstable, first give IV insulin variable drip and determine the requirement over 24 hours and then add all the insulin to the TPN bag Continue to supplement every 4 to 6 hours with SC rapid-acting insulin using BG – 100 / CF where CF is equal to 3000 divided by weight in kg. On average, CF = 30 to 40
Case 5: DM 1 Patient Going for Outpatient Surgery • What do you tell the patient to do? • Hold insulin • Take half their dose • Take their basal only with supplement if needed (>140 mg/dL) • Hold insulin and will start IV insulin
Case 6: DM 1 Patient in DKA(ph 7.0; BG 400 mg/dL: weight 80 kg) • What amount of fluids do you give immediately? • 1 liter saline • 2 liters saline • 1 liter 0.45% saline • 2 liters 0.45% saline
Case 6: DM 1 Patient in DKA (ph 7.0; BG 400 mg/dL: weight 80 kg) • Do you give NaCO3? • When do you start potassium and how much? • When do you start dextrose and how much? My preference is 2 liters saline followed by D50.45 saline with 40 meq KCL/liter at 250 mL/hr. Monitor electrolytes q4-8h