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 ( )

2. Outline
Background Data
Insulins
Protocols
Cases

3. 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

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. 2004;27(2):
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):

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. 2002;87(3):

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. 2000;355(9206):773-8.
Capes SE, Stroke. 2001;32(10):
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)

8. Cause or Effect? Intervention Studies

9. Post-CABG Patients Portland Protocol Study
On-going,17 year pre-post intervention study comparing conventional treatment with subcutaneous insulin ( ) vs. continuous insulin infusion ( ) 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: , 2003

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

11. 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: , 2003

12. SICU patients
Randomized controlled trial of intensive insulin infusion therapy to maintain BG mg/dl vs conventional therapy to maintain BG 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):

13. 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.

14. 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,
Smith, WD, Am J Health Syst Pharm Apr 1; 62(7):
Schoeffler JM, Ann Pharmacother Oct; 39(10)

15. 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

16. 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

17. 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

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

19. 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.

20. Glargine vs NPH Insulin6
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.

21. 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

22. 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

23. 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

24. 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

25. 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.

26. 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.

27. 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

28. Correction Factor Insulin
Premeal BG
Lispro
Insulin
1 unit
2 units
3 units
4 units
>320
5 units
Premeal BG
Lispro
Insulin
1 unit
3 units
5 units
7 units
>320
9 units
40 units insulin/day
41-80 units insulin/day

29. Correction Factor Insulin
Premeal BG
Lispro
Insulin
3 unit
5 units
7 units
9 units
>320
11 units
>80 units insulin/day

30. Correction Factor Insulin
Only HALF correction dose is given at bedtime

31. Goals for Ward Patients
Pre-prandial BS mg/dL
All BS <180 mg/dl

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

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

34. 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 mg/dl

35. 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

36. 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

37. 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

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. Case 1 Cont… Which correction factor algorithm will she require?
Medium Dose Algorithm
Premeal BG
Lispro
Insulin
1 unit
3 units
5 units
7 units
>320
9 units
41-80 units insulin/day

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

45. 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?

46. 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

47. 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.

48. 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?

49. 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

50. 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)

51. 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

52. 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

53. 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

54. 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!

55. 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.

56. 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?

57. 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?

58. 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 = 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!

59. 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

61. 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.