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
16.00%
16.0%
14.00%
12.00%
10.00%
8.00%
6.00%
4.00%
2.00%
0.00%
1.7%
Normoglycemia
3.0%
Known Diabetes
New
Hyperglycemia
•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 deepsternal 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
16.00%
14.5%
14.00%
12.00%
10.00%
Mortality
8.00%
6.0%
6.00%
4.1%
4.00%
2.00%
0.00%
2.3%
0.9%
1.3%
<150 150175
175200
200225
225- >250
250
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
12.00%
10.00%
ARR-3.4%
ARR-3.7%
8.00%
Intensive
Conventional
6.00%
4.00%
2.00%
0.00%
ICU
In-Hospital
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
Plasma insulin (µU/ml)
Physiological Serum Insulin
Secretion Profile
Breakfast
Lunch
Dinner
50
25
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
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
Onset
Lispro/Aspart
Regular
NPH/Lente
Glargine
Peak
Effective
Duration
<15 min
1 hr
3 hr
1/2-1 hr
2-3 hr
3-6 hr
2-4 hr
7-8 hr
10-12 hr
1-2 hr Flat/Predictable 24 hr
Short-Acting Insulin Analogs
Aspart
400
350
300
250
200
150
100
Regular
50
0
0
30 60 90 120 150 180 210 240
Plasma insulin (pmol/L)
Plasma insulin (pmol/L)
Lispro
500
450
400
350
300
250
200
150
100
50
0
Regular
0
50
Time (min)
Meal
SC injection
100 150
200
Time (min)
Meal
SC injection
Heinemann, et al. Diabet Med. 1996;13:625–629; Mudaliar, et al. Diabetes Care.
1999;22:1501–1506.
250
300
Glargine vs NPH Insulin
Glucose utilization rate
(mg/kg/h)
6
NPH
Glargine
5
4
NPH
3
2
Glargine
1
0
0
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
Plasma insulin
Breakfast
Lunch
Lispro
Dinner
Lispro
Lispro
Glargine
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
Insulin Requirements

Basal Insulin
 Baseline insulin needed
 ex. Glargine (Lantus®)

whether eating or NPO
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
130-170
171-220
221-270
271-320
>320
Lispro
Insulin
1 unit
2 units
3 units
4 units
5 units
40 units insulin/day
Premeal
BG
130-170
171-220
221-270
271-320
>320
Lispro
Insulin
1 unit
3 units
5 units
7 units
9 units
41-80 units insulin/day
Correction Factor Insulin
Premeal
BG
130-170
171-220
221-270
271-320
>320
Lispro
Insulin
3 unit
5 units
7 units
9 units
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

Make daily
adjustments of basal
insulin based on
fasting (AM) BG
Fasting BG Change to
Glargine
<70
71-90
90-130
131-180
181-230
231-280
>281
↓ 20%
↓10%
no change
↑ by 10%
↑ 20%
↑ 30%
↑ 40%
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 hyperglycemiamay 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 12%. 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

How much basal insulin (Lantus) should you
give?
 30

kg X 0.6 units/kg = 60 units
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?
Premeal Lispro
 Medium
Dose Algorithm
BG
130-170
171-220
221-270
271-320
>320
Insulin
1 unit
3 units
5 units
7 units
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

Decrease glargine (Lantus®) by 10%: 54 units SC
glargine daily
 Adjust

basal insulin
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
covered!
(Lantus) and Lispro (Humalog) now
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?

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)
ALERT & EATING
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. 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.