Intensive Management of Inpatient Hyperglycemia Nicole L' Artz, MD

1
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)
2
Outline

• Background Data
• Insulins
• Protocols
• Cases

3
Hyperglycemia Scenarios

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

4
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. 200427(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. 200287(3)978-82.

5
Background

• Why do we care about inpatient hyperglycemia?

6
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. 200287(3)978-82.

7

• 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. 2000355(9206)773-8. Capes SE,
Stroke. 200132(10)2426-32. Parsons MW, Ann
Neurol. 200252(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.
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Cause or Effect?Intervention Studies
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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

10
14.5
Mortality
6.0
4.1
2.3
1.3
0.9
Average postoperative glucose (mg/dl)
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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

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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.
2001345(19)1359-67.
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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 gt5 days of ICU
care.
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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.
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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

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Physiological Serum Insulin Secretion Profile
Breakfast
Lunch
Dinner
50
Plasma insulin (µU/ml)
25
400
800
1200
1600
2000
2400
400
800
Time
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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

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Pharmacokinetics of Current Insulin Preparations

• Effective
• Onset Peak Duration
• Lispro/Aspart lt15 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

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Short-Acting Insulin Analogs
Aspart
Lispro
400
500
450
350
400
300
350
250
300
Plasma insulin (pmol/L)
200
250
Plasma insulin (pmol/L)
200
150
150
100
Regular
100
50
Regular
50
0
0
0
30
60
90
120
180
210
150
240
0
50
100
150
200
300
250
Time (min)
Time (min)
Meal SC injection
Meal SC injection
Heinemann, et al. Diabet Med. 199613625629
Mudaliar, et al. Diabetes Care. 19992215011506.
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Glargine vs NPH Insulin
6
NPH
5
Glargine
4
NPH
Glucose utilization rate (mg/kg/h)
3
2
Glargine
1
0
0
10
20
30
Time (h) after SC injection
End of observation period
Lepore, et al. Diabetes. 199948(suppl 1)A97.
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Basal/Bolus Treatment with Rapid-acting
Long-acting Insulin Analogs
Breakfast
Lunch
Dinner
Lispro Lispro Lispro
Plasma insulin
Glargine
400
1600
2000
2400
400
800
1200
800
Time
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Insulin Requirements

• Basal 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

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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

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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

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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.

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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.

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Correction Factor Insulinthe 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

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Correction Factor Insulin
40 units insulin/day
41-80 units insulin/day
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Correction Factor Insulin
gt80 units insulin/day
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Correction Factor Insulin

• Only HALF correction dose is given at bedtime

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Goals for Ward Patients

• Pre-prandial BS 90-130 mg/dL
• All BS lt180 mg/dl

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Adjusting Basal Insulin

• Make daily adjustments of basal insulin based on
  fasting (AM) BG

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Adjusting Prandial Insulin

• Recalculate prandial insulin dose using new basal
  insulin amount divided by 3

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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

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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

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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

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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

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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.

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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.

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Discharge

• Patient with Type 2 Diabetes
• HbA1C gt7 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 lt7.
• Note Illinois public aid now covers Lispro
  (Humalog) and Glargine (Lantus) for outpaients.

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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.

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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.

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Case 1 Cont

• Which correction factor algorithm will she
  require?
• Medium Dose Algorithm

41-80 units insulin/day
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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.

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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?

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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

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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.

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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?

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Case 2

• The nurse reports the insulin gtt has been stable
  at 3 units/hr for the past 3 hrs and the
  patients 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

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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 (gt80 units insulin/day)

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Case 2

• You are called by the patients nurse. The
  patients 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

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Case 2

• The following day, the patients 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

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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

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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!

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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.

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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?

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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 patients BG
  at lunch is 65. She is awake and not
  symptomatic. How do you treat this?

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To Treat HYPOGLYCEMIA ( Blood Glucose Less than
70 mg/dl )
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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?

60
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

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• 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.