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Managing Hyperglycemia in Inpatients: Ensuring Success
Hospitalizations Account for Largest
Portion of Direct Cost of Diabetes Care
Current Guidelines and
Evidence for Inpatient
Hyperglycemic Control
2012 Total direct cost: $176 billion
Hospitalizations
Nursing home
31%
Curtis L. Triplitt, Pharm.D., CDE
Associate Director
Diabetes Research Center
Texas Diabetes Institute
Associate Professor
Department of Medicine, Division of Diabetes
University of Texas Health Science Center at San Antonio
San Antonio, Texas
Office visits
43%
ER visits
5%
Outpatient clinics
4%
9%
8%
Outpatient meds and
supplies
American Diabetes Association. Diabetes Care. 2013; 36:1033-46.
Enlargement on page 6
At what glucose level does your ICU
implement an IV insulin protocol, and
what is the glycemic target?
Guidelines from Professional Organizations on
ICU Blood Glucose (BG) Goal
Year
Patient
Population
Organization
BG Treatment
Threshold
(mg/dL)
BG
Target
(mg/dL)
BG
Hypoglycemia
Definition
(mg/dL)
Updated
since NICESUGAR,
2009
<70
Yes
2009
AACE and ADA
ICU
patients
180
140–180
2013
Surviving Sepsis
Campaign
ICU
patients
180
<180
2009
Institute for Healthcare
Improvement
ICU
patients
180
<180
<40
Yes
2012
American College of
Critical Care Medicine
(ACCM)
ICU
150
<150
(Trauma)
<180
(Stroke+)
<70
Yes
2013
American College of
Physicians
ICU patient
Not stated
140–200
Not stated
Yes
American Heart
Association
ICU
patients
with ACS
180
90–140
2008
Kavanagh BP et al. N Engl J Med. 2010; 363:2540-6.
Qaseem A et al. Ann Intern Med. 2011; 154:260-7.
Not stated
Not stated
a.
b.
c.
d.
e.
f.
Yes
No
Jacobi J. Crit Care Med. 2012; 40:3251-76.
Finfer S et al. N Engl J Med. 2009; 360:1283-97.
2009 AACE/ADA Target Inpatient Glucose
Levels and Hypoglycemia Definitions
BG Value
BG >200 mg/dL, target 80-110 mg/dL
BG >200 mg/dL, target 80-140 mg/dL
BG >180 mg/dL, target 140-180 mg/dL
BG in 200s mg/dL, target 140-180 mg/dL
Have protocol, but none of these fit
Have no ICU protocol or I don’t know
Definition
Guidelines for the use of an insulin infusion for
the management of hyperglycemia in critically ill
patients (ACCM)
Implications
>140 mg/dL
Hyperglycemia*
Premeal levels persistently above this
level may necessitate treatment
>180 mg/dL
Hyperglycemia
No random blood glucose levels should
be, in general, above this goal
<70 mg/dL
Hypoglycemia
Standard definition in outpatients,
correlates with the initial threshold for
release of counterregulatory hormones
<40 mg/dL
Severe
hypoglycemia
Increased mortality risk, cognitive
impairment begins at 50 mg/dL in normal
individuals
 In the population of critically ill injured (trauma) ICU patients, we
suggest that BG ≥ 150 mg/dL should trigger initiation of insulin
therapy, titrated to keep BG < 150 mg/dL for most adult trauma
patients and to maintain BG values absolutely < 180 mg/dL, using a
protocol that achieves a low rate of hypoglycemia (BG ≤ 70 mg/dL)
to achieve lower rates of infection and shorter ICU stays in trauma
patient
Hypoglycemia
 We suggest that a BG ≥ 150 mg/dL triggers initiation of insulin
therapy for most patients admitted to an ICU with the diagnoses
of ischemic stroke, intraparenchymal hemorrhage, aneurysmal
subarachnoid hemorrhage, or traumatic brain injury, titrated to
achieve BG values absolutely < 180 mg/dL with minimal BG
excursions <100 mg/dL, to minimize the adverse effects of
hyperglycemia
*Reassess insulin regimen if BG levels fall below 100 mg/dL
Occasional patients may be maintained with BG below and/or above these cut-points
AACE = American Association of Clinical Endocrinologists
ADA = American Diabetes Association
Moghissi ES et al.
Endocr Pract. 2009; 15:353-69.
Jacobi J et al. Crit Care Med. 2012; 40:3251-76.
1
Managing Hyperglycemia in Inpatients: Ensuring Success
Guidelines for the use of an insulin infusion for
the management of hyperglycemia in critically ill
patients (ACCM)
Guidelines for the use of an insulin infusion for
the management of hyperglycemia in critically ill
patients (ACCM)
 We suggest that BG ≤ 70 mg/dL are associated
with an increase in mortality, and that even brief
severe hypoglycemia (BG ≤ 40 mg/dL) is
independently associated with a greater risk of
mortality and that the risk increases with
prolonged or frequent episodes
 We suggest continuous insulin infusion (1 unit/mL)
therapy should be initiated after priming new
tubing with a 20-mL waste volume
 Subcutaneous (SC) insulin may be acceptable in
the ICU if BG goals are maintained
 Test and adjust BG every 1-2 hours - this has
not been studied prospectively
Jacobi J et al. Crit Care Med. 2012; 40:3251-76.
Jacobi J et al. Crit Care Med. 2012; 40:3251-76.
Surviving Sepsis:
Guidelines Differences
Surviving Sepsis Campaign
1. A protocolized approach to BG management in ICU
patients with severe sepsis commencing insulin
dosing when
 Initiate at 180 mg/dL, but no lower
threshold for glycemic control except
hypoglycemia
2 consecutive BG levels are >180 mg/dL
This protocolized approach should target an upper BG
≤180 mg/dL rather than an upper target BG ≤110 mg/dL
(grade 1A)
 No evidence for 140-180 mg/dL range
versus 110-140 mg/dL range except for
hypoglycemia
2. BG values should be monitored every 1–2 hr until
glucose values and insulin infusion rates are stable
and then every 4 hr thereafter (grade 1C)
3. Glucose levels obtained with point-of-care testing of
capillary blood should be interpreted with caution, as
such measurements may not accurately estimate
arterial blood or plasma glucose values (this
statement is ungraded)
Although all evidence taken into account,
NICE-SUGAR is the main trial that influences
Dellinger RP et al. Crit Care Med. 2013; 41:580-637.
Dellinger RP et al. Crit Care Med. 2013; 41:580-637.
American College of Physicians
American College of Physicians
 Recommendation 1: ACP recommends not using
intensive insulin therapy to strictly control blood
glucose in non-surgical intensive care unit
(SICU)/medical intensive care unit (MICU) patients
with or without diabetes mellitus (Grade: strong
recommendation, moderate-quality evidence)
 Recommendation 2: ACP recommends not using
intensive insulin therapy to normalize blood glucose
in SICU/MICU patients with or without diabetes
mellitus (Grade: strong recommendation, highquality evidence)
 Current evidence does not show a mortality benefit
associated with use of IIT to achieve a target of
normoglycemia (blood glucose levels of 4.4 to 6.1
mmol/L [80 to 110 mg/dL])
 Current evidence does not support 80 to 180 mg/dL compared with
higher or unspecified targets using a variety of intensive insulin
therapy regimens for patients with myocardial infarction, stroke, or
acute brain injury or those under perioperative care
 A nonsignificant reduction in the incidence of infection has been
observed
 Although the target blood glucose levels in the current trials ranged
widely, avoiding targets less than 7.8 mmol/L (<140 mg/dL) should
be a priority because harms are likely to increase at lower blood
glucose targets
 Evidence from some studies showed an increase in
mortality associated with IIT and hypoglycemia. Data on
the effects of IIT targeted to normoglycemia on reduction
in length of ICU stay are mixed
IIT = intensive insulin therapy
Qaseem A et al. Ann Intern Med. 2011; 154:260-7.
2
Qaseem A et al. Ann Intern Med. 2011; 154:260-7.
Managing Hyperglycemia in Inpatients: Ensuring Success
American College of Physicians
Striking the Right Balance
 Recommendation 3: ACP recommends a target blood
glucose level of 7.8 to 11.1 mmol/L (140 to 200 mg/dL)
if insulin therapy is used in SICU/MICU patients
(Grade: weak recommendation, moderate-quality
evidence)
 Summary - poorly controlled glucose worsens outcomes
 Evidence is not sufficient to give a precise range for blood glucose
levels
Hyperglycemia
Hypoglycemia
 140 to 200 mg/dL is associated with similar mortality outcomes as
intensive insulin therapy targeted at blood glucose levels of 80 to 110
mg/dL and is associated with a lower risk for hypoglycemia
 Current studies do not provide enough information to determine
whether allowing blood glucose levels to increase above 10.0 to 11.1
mmol/L (180 to 200 mg/dL) is associated with similar outcomes to
those seen at lower target levels
Qaseem A et al. Ann Intern Med. 2011; 154:260-7.
NICE-SUGAR:
Baseline Characteristics
NICE-SUGAR Study
 Multicenter-multinational randomized, controlled trial
(Australia, New Zealand, and Canada; N=6104 ICU
patients)





− Intensive BG target: 4.5-6.0 mmol/L (81-108 mg/dL)
− Conventional BG target: <10.0 mmol/L (180 mg/dL)
 Primary outcome: Death from any cause within 90
days after randomization
 Patient population
−
−
−
−
Age: ~60 years
Gender: ~36% female
Diabetes: ~20% (BMI ~28 kg/m2)
Interval, ICU admission to randomization: 13.4 hr
Reason for ICU admission
− Operative* ~37%
− Non-operative† ~63%
 Sepsis: ~22%
 Trauma: ~15%
Mean APACHE II score: ~21; APACHE >25: 31%
Reason for ICU admission: surgery: ~37%, medical: 63%
History of DM: 20% (T1DM: 8%, T2DM: 92%)
At randomization: sepsis: 22%, trauma: 15%
*No significant number of cardiothoracic surgery patients
†No significant number of CCU patients
Finfer S et al. N Engl J Med. 2009; 360:1283-97.
Finfer S et al. N Engl J Med. 2009; 360:1283-97.
Enlargement on page 6
Intensive Glycemic Control in Critically Ill
Adults: Severe Hypoglycemia Risk
NICE-SUGAR Study Outcomes
Intensive
Group
Conventional
Group
Morning BG (mg/dL)
118 ± 25
145 ± 26
Hypoglycemia
(BG ≤ 40 mg/dL)
206/3016
(6.8%)
15/3014
(0.5%)
28-Day mortality (P=0.17)
22.3%
20.8%
90-Day mortality (P=0.02)
27.5%
24.9%
Outcome Measure
Meta-analysis of 26 Randomized Controlled Trials (13,567 patients)
Study
Severe
Hypoglycemia
(≤ 40 mg/dL)
Favors IIT
Favors conventional control
Van den Berghe et al.8
Henderson et al.31
Bland et al.25
Van den Berghe et al.9
Mitchell et al.35
Azevedo et al.22
De La Rosa Gdel et al.12
Devos et al.13
Oksanen et al.36
Brunkhorst et al.11
Iapichino et al.32
Arabi et al.10
Mackenzie et al.33
NICE‐SUGAR18
Overall
0.1
1
10
Risk Ratio (95% CI)
Griesdale DE et al. CMAJ. 2009; 180:821-7.
Finfer S et al. N Engl J Med. 2009; 360:1283-97.
3
Managing Hyperglycemia in Inpatients: Ensuring Success
Pharmacists Need to Clearly
Understand
Guidelines from Professional
Organizations: Non-ICU Goals
Treatment goals
Treatment options
Treatment protocols
Potential medication errors and methods to
reduce errors
 Their important role on multidisciplinary team in
ensuring safe and effective management of
hyperglycemia in the hospital setting




Year
Organization
Patient
Population
2009
AACE and
ADA
Consensus
Statement
Noncritically ill
patients
2012
Endocrine
Society
Clinical
Practice
Guideline
Noncritically ill
patients
BG
Treatment
Threshold
BG
Target
Premeal
180 mg/dL <140
mg/dL
Premeal
180 mg/dL <140
mg/dL
BG Definition
of
Hypoglycemia
Updated
since
NICESUGAR
<70 mg/dL
(Reassess
treatment if
<100 mg/dL)
Yes
(Reassess
treatment if
<100 mg/dL)
Yes
Moghissi ES et al. Endocr Pract. 2009; 15:353-69.
Umpierrez GE et al. J Clin Endocrinol Metab. 2012; 97:16-38.
Adapted from Kelly JL. Am J Health-Syst Pharm. 2010; 67(Suppl 8):S9-16.
Discharge Planning:
New Hyperglycemia
Transition to Outpatient Status
 Begin discharge planning early
A1C
 Obtain A1C for discharge planning if result
not available from previous 2 to 3 months
<5.7%
− A1C can now also be used as a means
to make the diagnosis of diabetes
− This is often missed by inpatient team
5.7% to 6.4%
Patient has pre-diabetes (at risk); follow up
advisable; consider diabetes prevention strategies
6.5% to 7%
Patient has diabetes; can be treated with lifestyle
and consider metformin
7% to 9%
 Stabilize blood glucose before discharge
General Guidelines
Patient does not have diabetes nor pre-diabetes
>9%
Patient has diabetes and pharmacotherapy is
indicated
Most patients would likely benefit from basal-bolus
insulin regimen at discharge
Society of Hospital Medicine Glycemic Control Task Force.
Workbook for Improvement. URL in ref list.
Discharge Planning:
Diagnosed Diabetes
A1C
<7%
7% to 8%
Transition from Hospital to Home
 Reinstitute preadmission insulin regimen or oral
and non-insulin injectable antidiabetic drugs at
discharge for patients with acceptable
preadmission glucose control
General Guidelines
Continue pre-admission diabetes management
therapy plan
Increase dose of preadmission diabetes medications
and/or add a second or third oral agent or basal
insulin at bedtime
>8%
If on 2 diabetes medications, add basal insulin at
bedtime
>9% to 10%
Most patients should be on basal-bolus insulin at
discharge
 Initiate insulin administration in those for whom it
is indicated at least one day before discharge to
allow assessment of efficacy and safety of this
transition
 Provide patients and their families or caregivers
with both oral and written instructions regarding
glycemic regimen
Society of Hospital Medicine Glycemic Control Task Force.
Workbook for Improvement. URL in ref list.
4
Managing Hyperglycemia in Inpatients: Ensuring Success
“Survival Skills”
to Teach Before Discharge
 How and when to take
medication or insulin
− What to expect from the
medication
− Confirm insurance
reimbursement
 How and when to test BG
− What are target glucose
levels
 Basics on meal planning
 How to treat and prevent
hypoglycemia
Conclusion
 Hyperglycemia
− Common in critically ill patients, both with and without
diabetes
− Predictor of adverse outcomes, including mortality
 Sick-day management plan
 Date and time of
follow-up visits
− Including diabetes
education
 Good, but not stringent, glucose control is most
common strategy among different guidelines
 When and who to call on
the health care team
 Hypoglycemia should be avoided, as adverse
mortality consequences may result
− Schedule follow up with
clinician (timely manner)
− Emergency numbers
− Available community
resources
 Pharmacists can and should be part of
multidisciplinary glycemic control team and
discharge planning in their institution
Moghissi E et al. Endocr Pract. 2009; 15:353-69.
Umpierrez GE et al. J Clin Endocrinol Metab. 2012; 97:16-38.
5
Managing Hyperglycemia in Inpatients: Ensuring Success
Guidelines from Professional Organizations on
ICU Blood Glucose (BG) Goal
Year
Patient
Population
Organization
BG Treatment
Threshold
(mg/dL)
BG
Target
(mg/dL)
BG
Hypoglycemia
Definition
(mg/dL)
Updated
since NICESUGAR,
2009
<70
Yes
2009
AACE and ADA
ICU
patients
180
140–180
2013
Surviving Sepsis
Campaign
ICU
patients
180
<180
2009
Institute for Healthcare
Improvement
ICU
patients
180
<180
<40
Yes
2012
American College of
Critical Care Medicine
(ACCM)
ICU
150
<150
(Trauma)
<180
(Stroke+)
<70
Yes
2013
American College of
Physicians
ICU patient
Not stated
140–200
Not stated
Yes
2008
American Heart
Association
ICU
patients
with ACS
180
90–140
Kavanagh BP et al. N Engl J Med. 2010; 363:2540-6.
Qaseem A et al. Ann Intern Med. 2011; 154:260-7.
Not stated
Not stated
Yes
No
Jacobi J. Crit Care Med. 2012; 40:3251-76.
Finfer S et al. N Engl J Med. 2009; 360:1283-97.
Intensive Glycemic Control in Critically Ill
Adults: Severe Hypoglycemia Risk
Meta-analysis of 26 Randomized Controlled Trials (13,567 patients)
Study
Severe
Hypoglycemia
(≤ 40 mg/dL)
Favors IIT
Favors conventional control
Van den Berghe et al.8
Henderson et al.31
Bland et al.25
Van den Berghe et al.9
Mitchell et al.35
Azevedo et al.22
De La Rosa Gdel et al.12
Devos et al.13
Oksanen et al.36
Brunkhorst et al.11
Iapichino et al.32
Arabi et al.10
Mackenzie et al.33
NICE‐SUGAR18
Overall
0.1
1
10
Risk Ratio (95% CI)
Griesdale DE et al. CMAJ. 2009; 180:821-7.
6
Managing Hyperglycemia in Inpatients: Ensuring Success
Enlargement on page 13
Types of Insulin
Practical Approach to
Inpatient Glycemic Control
Kevin W. Box, Pharm.D.
Senior Clinical Pharmacist
UC San Diego Health System
San Diego, California
Diabetes Education Online: Diabetes Teaching Center at the University of California,
San Francisco. Table of insulin action. URL in ref list. Used with permission.
HPI: 54 y/o, 100-kg man with T2DM x 8 yr
admitted with diabetes-related foot
infection, eating regular meals
 Outpatient Meds
On admission what would you do?
a. Continue home regimen of metformin,
glipizide, and NPH
b. Continue metformin and glipizide at half of
outpatient dose
c. Withhold oral meds; start glargine 30 units
daily, lispro 10 units qac, and moderate
correctional scale
d. Withhold oral meds; start high correctional
scale only
 Pertinent Labs
− Glipizide 10 mg po daily
− Metformin 1000 mg po
twice daily
− NPH insulin 20 units
subcutaneously at
bedtime
− A1C 10%
− BG in ED 240 mg/dL
Stepwise Approach to Physiologic
Insulin Dosing
Withhold All Oral Agents
 Non-insulin agents are inappropriate in
most hospitalized patients
Moghissi ES et al. Diabetes Care. 2009; 32:1119-31.
7
Step 1
Estimate amount of insulin patient would need
over one day, if getting adequate nutrition =
total daily dose (TDD)
Step 2
Assess patient’s nutritional situation
Step 3
Decide which components of insulin the patient
will require and percentage of TDD each should
represent
Step 4
Assess blood glucose at least daily, adjusting
insulin doses as appropriate
Managing Hyperglycemia in Inpatients: Ensuring Success
STEP 1: Estimate the amount of insulin the
patient would need over one day, if getting
adequate nutrition = TDD
Our Patient
 Calculate TDD
 Insulin drip-based estimate (for patients treated with an insulin
infusion)
 For patients already treated with insulin, consider the patient’s
preadmission subcutaneous regimen and glycemic control on that
regimen
 Weight-based estimate
− No drip
− On orals and NPH as outpatient
− Weight
 100 kg (0.6 units/kg) = 60 units
 100 kg (0.5 units/kg) = 50 units
− TDD = 0.4 units/kg x Wt in kg
− Adjust down to 0.3 units/kg x Wt in kg for those with hypoglycemia
risk factors, including kidney failure, type 1 diabetes (especially if lean),
frail/low body weight/ malnourished elderly, or insulin naïve patients
− Adjust up to 0.5-0.6 units/kg (or more) x Wt in kg for those with
hyperglycemia risk factors, including obesity and high-dose
glucocorticoid treatment
Enlargement on page 13
Which pattern of nutrition does your
patient fit into?
STEP 2: Assess the patient’s nutritional
situation
 Eating meals or receiving bolus tube feedings
Eating
 Eating meals but with unpredictable intake
 Getting continuous tube feedings
 Getting tube feedings for only part of the day
 Getting parenteral nutrition
 NPO
Tube
feedings
NPO
STEP 3: Decide which components of
insulin the patient will require and percentage
of TDD each should represent
Our Patient
 Eating regular meals
 Basal insulin can generally be estimated to be
half of the TDD
 Nutritional insulin makes up remaining half of
the TDD
50:50
8
Managing Hyperglycemia in Inpatients: Ensuring Success
STEP 3: Decide which components of
insulin the patient will require and percentage
of TDD each should represent
Our Patient
 Step 1: TDD
− Weight 100 kg (0.6 units/kg) = 60 units
 In most cases, basal insulin should be provided
 Step 2: Nutrition pattern
 When a patient is not receiving nutrition, nutritional
insulin should not be given
 Step 3: Insulin components and ratio
− Eating regular meals
 Nutritional insulin needs must be matched to the
actual nutritional intake
− 50:50
 In most cases, well-designed corrective insulin
regimens should be provided
− Bolus – lispro 10 units qac
− Basal – glargine 30 units
− Correction scale - lispro qac and qhs (moderate-high)
qac = before every meal
qhs = at bedtime
Enlargement on page 14
Correction Insulin
Low Dose Correction
STEP 4: Assess blood glucose at least daily,
adjusting insulin doses as appropriate
Moderate Dose Correction
 Blood glucose targets can only be achieved via
continuous management of the insulin program
1:50 >150 mg/dL qac
and >200 mg/dL qhs
High Dose Correction
1:25 >150 mg/dL qac
and >200 mg/dL qhs
There is no “autopilot” insulin regimen for a
hospitalized patient!
1:25 >150 mg/dL, starting at 3 units qac and >200mg/dL, starting at 4 units qhs
What insulin regimen would you
use now?
Our Patient
 Overnight the patient decompensated on
the floor (blood pressure 98/55 mm Hg),
and a rapid response was called
a. Continue current glycemic regimen
b. Withhold all subcutaneous insulin and
start IV insulin infusion
c. Restart home NPH of 20 units
subcutaneous at bedtime
d. 2 units regular insulin every 1 hour
subcutaneous until BG <150 mg/dL
− Transferred to ICU, started on norepinephrine
drip at 10 mcg/min, and intubated
 Blood glucose levels during the night
− 201 mg/dL (2400)
− 248 mg/dL (0600)
9
Managing Hyperglycemia in Inpatients: Ensuring Success
Enlargement on page 14
Our Patient:
Glucose Management Report
Our Patient
 Patient extubated, off pressors
 Team would like recommendations to
transfer off insulin drip so he can go to
floor
Transition Step 1
Our Patient: IV Insulin Administration
BG
(mg/dL)
Insulin infusion rate
(units/hr)
Is the patient ready for transition?
Patient is not critically ill or requiring pressors
Blood glucose in target range all of last 6 hours
Transition Step 2
No
Yes
Continue Insulin
Drip
Continue to step
2
Transition Step 3
Does patient need scheduled subcutaneous insulin?
Calculate total daily dose insulin requirement
(TDD)
No
Patients with no history of diabetes and A1c <6%
Yes
All patients with T1DM
Patients with T2DM and insulin rate >1 unit/hour
Patients with A1c >6%
TDD = (average drip rate)_____ units/hr x 20 hr
Note: approximately 80% of 24 hr = 20 hr
No
Yes
Transition to correction
scale only
Continue to Step 3
10
Managing Hyperglycemia in Inpatients: Ensuring Success
Transition Step 3
Approximate 6-hour total = 14.7 units
BG
(mg/dL)
Insulin
infusion rate
(units/hr)
Calculate total daily dose insulin requirement
(TDD)
14.7 units / 6 hours = 2.5 units/hour
TDD = (average drip rate) 2.5 units/hr x 20 hr
TDD = 50 units
Transition Step 4
Full Nutrition
 Full nutrition: Patient is currently eating
>50% of his/her meals, on goal parenteral
nutrition or tube feedings, dextrose IV fluid
>50 mL/hr
• Patient currently eating
>50% of his/her meals
• On goal TPN or tube
feeds
• Dextrose IV fluid >50
mL/hr
 Minimal nutrition: Patient is currently NPO,
eating <50% of his/her meals, is on a zero
carbohydrate clear liquid diet, or 6 hours
used in step 3 calculation is a period of
fasting (overnight)
Minimal Nutrition:
Our Patient:
Designing Transition Regimen
Calculated insulin = basal insulin
• Patient currently NPO
or eating<50% of his/her
meals
• Zero carbohydrate clear
liquid diet
• 6 hours used in step 3
calculation is period of
fasting (overnight)
• Give 50% of TDD as
basal insulin 2 hr
before stopping
infusion
• Give 50% of TDD as
nutritional insulin
divided TID if tolerating
meals (lispro) or every
6 hr if on continuous
tube feeds (regular)
• Correction scale
 Transition step 1: Patient is ready to transition
 Transition step 2: A1C 10%, patient needs scheduled
insulin
 Transition step 3: TDD = 50 units (weight based 50-60
units)
• Give 100% TDD as
basal insulin 2 hr
before stopping
infusion
• Add nutritional
insulin when
clinically indicated
• Correction scale
 Transition step 4: Eating regular meals
Insulin components and ratio
50:50
− Basal – glargine 25 units
− Bolus – lispro 8 units qac
− Correction scale – lispro qac and qhs (moderate)
11
Managing Hyperglycemia in Inpatients: Ensuring Success
Transition Step 5
Conclusion
 Protocols every institution should have
 Assess blood glucose values at least daily,
adjusting insulin doses as appropriate
− How to initiate a basal-bolus insulin regimen
− Continuous IV insulin infusion
− Transition from IV insulin infusion to a basal
bolus regimen
− Hypoglycemia
− Nutrition on hold unexpectedly
− Diabetic ketoacidosis
− Continuous quality improvement monitoring
12
Managing Hyperglycemia in Inpatients: Ensuring Success
Types of Insulin
Diabetes Education Online: Diabetes Teaching Center at the University of California,
San Francisco. Table of insulin action. URL in ref list. Used with permission.
Which pattern of nutrition does your
patient fit into?
Eating
Tube
feedings
NPO
13
Managing Hyperglycemia in Inpatients: Ensuring Success
Correction Insulin
Low Dose Correction
1:50 >150 mg/dL qac
and >200 mg/dL qhs
Moderate Dose Correction
High Dose Correction
1:25 >150 mg/dL qac
and >200 mg/dL qhs
1:25 >150 mg/dL, starting at 3 units qac and >200mg/dL, starting at 4 units qhs
Our Patient:
Glucose Management Report
14
Managing Hyperglycemia in Inpatients: Ensuring Success
Overview
Issues and Special
Populations for Inpatient
Glycemic Management
 Identify controversies in goal glucose
values in patient specific populations
 Determine whether patients in specific
situations are at greater or lesser risk of
hyperglycemia or hypoglycemia
 Examine approaches for managing
hyperglycemia in special populations of
hospitalized patients
Paul M. Szumita, Pharm.D., BCPS
Clinical Pharmacy Practice Manager
Director, Critical Care Pharmacy Residency
Brigham and Women’s Hospital
Boston, Massachusetts
What is your opinion on the goal
glucose in critical care setting?
a. Guidelines have it right on the money
b. Would like goal glucose higher than
current guideline
c. Would like goal glucose lower than
current guideline
d. Would like another large RCT to put
controversy to bed
ICU Goal Glucose Controversy
Hypoglycemia and Mortality:
Australian Database Analysis
Hyperglycemia and Mortality:
Stamford Hospital Analysis
45
Mortality Rate (%)
40
Hypoglycemia
35
Incidence
(%)
Hospital
Mortality (%)
Adjusted OR
(95% CI)*
30
None
92.9
15.7%
1.0
25
< 73 mg/dL
6.2
29.5%
1.5 (1.3-1.6)
< 40 mg/dL
0.9
57.4%
2.6 (2.1-3.2)
20
15
*Covariate adjustment for age, sex, surgical status, primary diagnosis, comorbid illness,
APACHE II, mechanical ventilation, acute kidney injury, and hospital site
10
5
0
80–99
100–119
120–139
140–159
160–179
180–199
200–249
250–299
Similar trends were seen when patients were stratified by MICU, SICU,
cardiothoracic ICU, and sepsis
> 300
Mean Glucose Value (mg/dL)
Database analysis of 24 Australian ICUs and 66,184 adult ICU admissions for >24
hours from January 1, 2000, to December 31, 2005
Single center retrospective analysis of 1,826 consecutive MICU/SICU patients, whole blood
glucose values during ICU stay, October 1, 1999 - April 4, 2002
Krinsley JS. Mayo Clin Proc. 2003; 78:1471-8.
Bagshaw SM et al. Crit Care Med. 2009; 37:463-70.
15
Managing Hyperglycemia in Inpatients: Ensuring Success
Enlargement on page 23
Leuven I
Leuven II
VISEP
Glucontrol
NICE SUGAR
SICU
MICU
Sepsis Mixed
ICU
Mixed
Protocol Heterogeneity
Mixed
Centers
1
1
18
19
42
Sample size
1548
1200
488/537
1011
~6030
Diabetic
~13%
~17
~30%
~19%
~20%
Excluded
14
863
1,612
?
34,067
Stopped early
No
No
Yes
Yes
No
Primary diet
TPN 85%
TPN 85%
60% TPN
27% TPN
25% TPN
APACHE II
~9
~23
~20
~15
~21
Mortality
ICU: ~ 7%
Hos: ~10%
ICU: ~25%
Hos: ~40%
28 Day: ~27%
ICU: ~16%
Hos: ~22%
28 Day: ~21%
Hypoglycemia
IIT: 5%
Control: 2%
IIT: 18.7 %
Control: 3.1%
IIT: 17%
Control: 4.1 %
IIT: 9.8
Control: 2.7%
IIT: 6.8 %
Control: 0.5%
Protocol
Leuven
Leuven
Leuven
Variable ?
NICE
Target (mg/dL)
80-110
80-110
80-110
80-110
81-108
Control (mg/dL)
Timing
Duration
< 180
< 180
< 180
140-180
144-180
ICU admit
ICU admit
< 12 hrs
?
< 24 hrs
ICU stay
ICU stay
ICU/ 21 days
ICU or 56 days
Eating or 90
days
Mortality in RCTs Targeting 80-110 mg/dL
30
Mortality Rate (%)
ICU
25
5
Mortality Rate (%)
27.5
24.9
25.6
8
4.8
P = 0.31
P = 0.74
Leuven
MICU*
VISEP**
P = 0.5
P = 0.02
P < 0.04
Glucontrol*
NICESUGAR***
van den Berghe G et al. N Engl J Med. 2001; 345:1359-67; van den Berghe G et al. N Engl J
Med. 2006; 354:449-61; Brunkhorst FM et al. N Engl J Med. 2008; 358:125-39; Preiser JC et al.
Intensive Care Med. 2009; 35:1738-48; Finfer S et al. N Engl J Med. 2009; 360:1283-97.
Intensive Insulin Therapy in
Critically Ill Surgical Patients
38.1
31.3
Mortality
Sepsis
Dialysis
Blood
Transfusion
Polyneuropathy
22.122.3
20.2
10.6
Not available
P = 0.05
Reduction
(%)
Not available
P = 0.95
34%
Leuven SICU Leuven MICU
> 5days*
> 3 days*
31% of cohort
Control
16.7
15.2
10
Mortality in Patients with Extended
ICU Stay
*ICU
Intensive Control
P = 0.005
24.7
15
Leuven
SICU*
van den Berghe G et al. N Engl J Med. 2001; 345:1359-67;
van den Berghe G et al. N Engl J Med. 2006; 354:449-61; Brunkhorst FM et al. N Engl J Med. 2008; 358:125-39;
Preiser JC et al. Intensive Care Med. 2009; 35:1738-48; Finfer S et al. N Engl J Med. 2009; 360:1283-97.
**28 day
***90 day
Intensive
26.8
24.2
20
0
IIT = intensive insulin therapy
45
40
35
30
25
20
15
10
5
0
*ICU
**28 day
***90 day
63% of cohort
VISEP > 5
days**
Glucontrol*
NICESUGAR***
41%
46%
44%
50%
92% of cohort
van den Berghe G et al. N Engl J Med. 2001; 345:1359-67; van den Berghe G et al. N Engl J
Med. 2006; 354:449-61; Brunkhorst FM et al. N Engl J Med. 2008; 358:125-39; Preiser JC et al.
Intensive Care Med. 2009; 35:1738-48; Finfer S et al. N Engl J Med. 2009; 360:1283-97.
van den Berghe G et al. N Engl J Med. 2001; 345:1359-67.
Intensive Insulin Therapy in
Medical ICU Patients
NICE SUGAR:
More Morbidity = More Mortality?
 Mortality
Morbidity Outcome
- Significantly reduced in patients in ICU ≥ 3 days
Days mechanical
ventilation, mean ± SD
 Morbidity significantly reduced in all patients
- Decreased weaning time from mechanical ventilation
- Decreased time to discharge from ICU
- Decreased time to discharge from the hospital
Intensive
n=3014
Conventional
n=3011
P Value
6.6 ± 6.6
6.6 ± 6.5
0.56
(+) Blood culture
12.8%
12.4%
0.57
Renal-replacement therapy
15.4%
14.5%
0.34
Red blood cell transfusion
42.1%
41.3%
0.56
Polyneuropathy not reported
What is the mechanism behind the small, but statistically significant increase
in mortality with intensive insulin therapy at 90 days in NICE SUGAR?
van den Berghe G et al. N Engl J Med. 2006; 354:449-61.
Finfer S et al. N Engl J Med. 2009; 360:1283-97.
16
Managing Hyperglycemia in Inpatients: Ensuring Success
Glycemic Separation in “Good”
RCTs Targeting 80-110 mg/dL
Intensive
Hypoglycemia in RCTs Targeting
80-110 mg/dL
Control
Hypoglycemia defined < 40 mg/dL
153
160
153
151
140
120
100
80
103
P < 0.001
112
111
P < 0.001
P < 0.001
147
145
119
118
P < 0.001
P < 0.001
% Patients
Mean glucose (mg/dL)
180
60
40
20
71 vs. 33 units/day
59 vs. 10 units/day
32 vs. 5 units/day
43 vs. 10 units/day
50 vs. 17 units/day
Leuven
MICU*
VISEP*
Glucontrol
NICESUGAR*
0
Leuven
* AM glucose SICU*
Intensive
Control
18.7
17
All variables P < 0.001
9.8
6.8
5
2
3.1
4.1
2.7
0.5
Leuven SICU Leuven MICU
VISEP
Glucontrol NICE-SUGAR
van den Berghe G et al. N Engl J Med. 2001; 345:1359-67; van den Berghe G et al. N Engl J
Med. 2006; 354:449-61; Brunkhorst FM et al. N Engl J Med. 2008; 358:125-39; Preiser JC et al.
Intensive Care Med. 2009; 35:1738-48; Finfer S et al. N Engl J Med. 2009; 360:1283-97.
van den Berghe G et al. N Engl J Med. 2001; 345:1359-67; van den Berghe G et al. N Engl J Med.
2006; 354:449-61; Brunkhorst FM et al. N Engl J Med. 2008; 358:125-39; Preiser JC et al.
Intensive Care Med. 2009; 35:1738-48; Finfer S et al. N Engl J Med. 2009; 360:1283-97.
Barriers to Inpatient Glucose
Management
No Ideal Protocol in the Literature
 Many have been described
 Few have been rigorously evaluated
 Few published protocols were ever
designed to reach blood glucose goal of
80-110 mg/dL
Heath care system and workers
No consensus regarding goals
No published “how to”
No standardized approach to testing and treatment
Inadequate insulin drip protocol
Lack of compliance
Fear of hypoglycemia
Culture
Accuracy of point-of-care testing (POCT)
Lack of education
Poor communication
Lack of health care resources












20
18
16
14
12
10
8
6
4
2
0
Anger KE et al. Pharmacotherapy. 2006; 26:214-28.
Examples of Published IV Insulin
Protocols





Yale1
Markovitz2
Leuven3
Portland4
Texas Diabetes Council5





The “Fixed” Protocol
Blood
Glucose
(mg/dL)
DIGAMI6
University of Washington7
Krinsley8
Rush University Protocol9
Northwestern University10
< 50
1Goldberg
PA et al. Diabetes Care. 2004; 27:461-7.
2Markovitz LJ et al. Endocr Pract. 2002; 8:10-8.
3van den Berghe G et al. N Engl J Med. 2001; 345:1359-67.
4Furnary AP et al. Endocr Pract. 2004; 10(Suppl 2):21-33.
5Texas Diabetes Council. October 25, 2007. URL in ref list.
6Malmberg K et al. Circulation. 1999; 99:2626-32.
7Ku SY et al. Jt Comm J Qual Patient Saf. 2005; 31:141-7.
8Krinsley JS. Mayo Clin Proc. 2004; 79:992-1000.
9Donaldson S et al. Diabetes Educ. 2006; 32:954-62.
10DeSantis AJ et al. Endocr Pract. 2006; 12:491-505.
Action
• Stop insulin; give 25 mL of 50% dextrose; recheck BG in 30 minutes
• When BG >75 mg/dL, restart with rate 50% of previous rate
50 – 75
• Stop insulin; if previous BG >100 mg/dL, then give 25 mL of 50%
dextrose; recheck BG in 30 minutes
• When BG >75 mg/dL, restart with rate 50% of previous rate
76 –100
• If <10 mg/dL lower than last test, decrease rate by 0.5 units/hr
• If >10 mg/dL lower than last test, decrease rate by 50%
• If ≥ last test result, maintain same rate
101 – 150
• Same rate
151 – 200
• If 20 mg/dL lower than previous test, same rate
• If higher than previous test, increase by 0.5 units/hr
> 200
• If ≥30 mg/dL lower than last test, use same rate
• If <30 mg/dL lower than last test (OR if higher than last test), increase
rate by 1 unit/hr
Furnary AP et al. Endocr Pract. 2004; 10(Suppl 2):21-33.
17
Managing Hyperglycemia in Inpatients: Ensuring Success
Multiplication Factor Concept
“Multiplier” Protocol Concept:
A Simple Calculation
CURRENT RATE
X
ADJUSTMENT FACTOR
 (Blood glucose – 60) X multiplication factor
= new insulin infusion rate for that hour
- The multiplication factor used in the equation
changes depending on the rate of change in
glucose value over time
(this factor based on rate of change in
BBG over time)
=
NEW RATE
Osburne RC et al. Diabetes Educ. 2006; 32:394-403.
Davidson PC et al. Diabetes Care. 2005; 28:2418-23.
BBG = bedside blood glucose
What is your opinion on the
importance of the diagnosis of
diabetes on goal glucose?
Non-Diabetics vs. Diabetics
 Adaptive mechanisms developed in the setting
of chronic hyperglycemia in diabetic patients
may decrease morbidity and mortality
associated with stress-induced hyperglycemia
a. All patients should have the same goal
(regardless of diagnosis of diabetes)
b. Patients with diabetes should have lower
goal
c. Patients without diabetes should have
lower goal
Krinsley JS et al. Curr Opin Clin Nutr Metab Care. 2012; 15:151-60.
Krinsley JS et al. Crit Care. 2013; 17:R37.
Association Between Mean Blood
Glucose and In-Hospital Mortality
No diabetes
0.8
Without Diabetes
0.4
All patients
Diabetes
0.2
0
With Diabetes
50
50
Percentage Mortality
0.6
Percentage Mortality
Mortality Rate
Patients With Diabetes vs.
Patients Without Diabetes
25
0
80-110
110-140
140-180
Mean BG (mg/dL)
>180
25
0
80-110
110-140
140-180
>180
Mean BG (mg/dL)
Mean Glucose (mg/dL)
Krinsley et al. Crit Care. 2013; 17:R37 (adapted).
Kosiborod M et al. Circulation. 2008; 117:1018-27 (adapted).
18
Managing Hyperglycemia in Inpatients: Ensuring Success
Diabetes vs. No Diabetes
2013 DM vs. No-DM in ICU
Diabetics
 Trial design
0.16
Mortality Probability
- Multi-center, retrospective, cohort analysis from 12
ICUs in eight different hospitals part of the
Intermountain Healthcare system
- Approved by the Intermountain investigational review
board
0.14
80-110 mg/dL
0.12
0.10
0.08
90-140 mg/dL
0.06
0.04
0.02
0
0 2
4
6
8 10 12 14 16 18 20 22 24 26 28 30
Days Post ICU Admission
Lanspa MJ et al. Chest. 2013; 143:1226-34.
Lanspa MJ et al. Chest. 2013; 143:1226-34 (adapted).
Insulin Needs in Special Patient
Populations
Diabetes vs. No Diabetes
Non‐diabetics
Mortality Probability
0.16
 Patients receiving high dose steroids
 Patients receiving enteral or parenteral
nutrition
 Patients undergoing surgery
90-140 mg/dL
0.14
0.12
0.10
0.08
80-110 mg/dL
0.06
0.04
0.02
0
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30
Days Post ICU Admission
Lanspa MJ et al. Chest. 2013; 143:1226-34 (adapted).
Optimizing Care of the Inpatient
with Hyperglycemia Is Challenging!
Case Scenario: Steroids
 78-year-old woman hospitalized for
worsening dyspnea and cough
 Inpatient situations are unstable
 No single algorithm is suitable for all
patients
 Many scenarios require increased
monitoring and possible adjustments in
insulin dose
 Chronic obstructive pulmonary disease
(COPD) since age 55
 No prior history of diabetes
- A1C 6.2%
 Started on methylprednisolone 40 mg IV
every 6 hr
 BG on day 2 climbs to 210 mg/dL
19
Managing Hyperglycemia in Inpatients: Ensuring Success
Basal Bolus Therapy with Emphasis
on Nutritional Insulin
Hyperglycemia and Steroids
 Common complication of glucocorticoid therapy
- Prevalence 20-50% among patients without prior history of
diabetes
 Medium-dose glucocorticoids (40-60
mg/day) tend to cause minimal increase in
FPG and marked elevation in PPG
 Results from
- Increases in hepatic glucose production
- Impairment of glucose uptake in peripheral tissues
 All of this contributes to increases in postprandial
glucose
 Predictors
- Total glucocorticoid dose
- Duration of glucocorticoid therapy
- Increasing age
FPG = fasting plasma glucose
PPG = postprandial plasma glucose
Umpierrez GE et al. J Clin Endocrinol Metab. 2012; 97:16-38.
Clore JN et al. Endocr Pract. 2009; 15:469-74.
Clement S et al. Diabetes Care. 2004; 27:553-91.
Moghissi ES et al. Endocr Pract. 2009; 15:353-69.
Hyperglycemia and Glucocorticoid
Therapy: Summary
Case Scenario: Total Parenteral
Nutrition (TPN)
 Institute glucose monitoring for at least 48
hours in all patients
 55-year-old obese man admitted for
hemorrhagic pancreatitis, no prior
history of diabetes
 BG 200 mg/dL on admission
 A1C 7.5% (previously unrecognized DM)
 Patient not eating, anticipated he will not
be able to eat for one week
 Total parenteral nutrition started
- Add or adjust insulin regimen based on
monitoring results
 During initiation and tapering of steroid
therapy, proactive adjustment of insulin
therapy can help avoid uncontrolled
hyperglycemia and hypoglycemia
Umpierrez GE et al. J Clin Endocrinol Metab. 2012; 97:16-38.
Moghissi ES et al. Endocr Pract. 2009; 15:353-69.
General Recommendations: Hyperglycemia
Associated with Parenteral Nutrition (PN)
TPN, Glucose, and Patient Mortality
Study
Hyperglycemia
Definition
(mg/dL)
 For patients receiving PN, regular insulin
administered as part of PN formulation can be both
safe and effective
 Subcutaneous correction-dose insulin is often used
in addition to insulin mixed with the PN
- When starting PN, the initial use of a separate
insulin infusion can help in estimating the
required total daily dose of insulin
 Separate IV insulin infusions may be needed to treat
marked hyperglycemia during PN
Mortality
Odds Ratio
Cheung (2005)
> 164
10.9
Lin (2007)
Sarkisian (2010)
> 180
≥ 180
5.0
7.22
Pasquel (2010)
> 180
2.80
Olveira (212)
> 180
5.6
Cheung NW et al. Diabetes Care. 2005; 28:2367-71.
Lin LY et al. Am J Med Sci. 2007; 333:261-5.
Sarkisian S et al. Can J Gastroenterol. 2010; 24:453-7.
Pasquel FJ et al. Diabetes Care. 2010; 33:739-41.
Olveira G et al. Diabetes Care.35
2013; 36:1061-6.
Umpierrez GE et al. J Clin Endocrinol Metab. 2012; 97:16-38.
Moghissi ES et al. Endocr Pract. 2009; 15:353-69.
20
Managing Hyperglycemia in Inpatients: Ensuring Success
Case Scenario: Tube Feedings
Complications of Enteral Nutrition
Prospective and observational study in 64 patients (mean age 76.2 yr)
receiving EN on internal medicine inpatient unit
Percent of patients
 70-year-old woman admitted with
a stroke
 Prior history of type 2 diabetes mellitus
- Controlled on oral agents
 BG 150 mg/dL on admission, A1C 7%
 Currently unable to swallow
 Continuous enteral nutrition started on
hospital day 2
60%
50%
40%
30%
20%
10%
0%
49%
Most frequent complications
46%
35%
33%
30%
20%
13%
3%
Should blood glucose levels be checked in patients receiving enteral nutrition?
Pancorbo-Hidalgo PL et al. J Clin Nurs. 2001; 10:482-90.
Glycemic Management of the
Patient Receiving Enteral Nutrition
Case Scenario: Surgery
 60-year-old woman with type 2 diabetes
mellitus treated with insulin is admitted for
hip fracture
 Continuous enteral nutrition (EN)
- Basal: 40-50% of TDD as long- or intermediate-acting insulin
given once or twice a day
- Short-acting insulin 50-60% of TDD given every 6 hr
- Admission glucose = 180 mg/dL
 Cycled enteral nutrition
- Intermediate-acting insulin given together with a rapid- or short-acting
insulin with start of tube feeding
- Rapid- or short-acting insulin administered every 4-6 hr
for duration of EN administration
- Correctional insulin given for BG above goal range
 Bolus enteral nutrition
- Rapid-acting or short-acting insulin given prior to each bolus feeding
Umpierrez GE et al. J Clin Endocrinol Metab. 2012; 97:16-38.
Basal-Bolus vs. Sliding Scale Insulin
in RABBIT 2 Surgery Study
Basal-Bolus Superior to Sliding Scale Insulin (SSI)
Treatment for Inpatient Hyperglycemia
Mean BG (mg/dL)
240
Achievement of
Glucose Goals
220
*
200
*
*
180
†
†
†
†
140
Basal-bolus
insulin
120
100
2
3
4
5
6
7
8
9
10
Days of Therapy
No differences in rate of hypoglycemia or hospital length of stay
*P
Hospital
Complications*
BG <70
mg/dL
BG <40
mg/dL
Basal
bolus
8.6%
23.1%
3.8%
Sliding
scale
24.3%
4.7%
0%
P value
0.003
< 0.001
0.057
SSI
160
Admit 1
Outcomes and Hypoglycemia
*Composite of postoperative complications
including wound infection, pneumonia,
bacteremia, respiratory, and acute renal
failure
< 0.01, †P < 0.05. Error bars denote standard deviation.
Insulin glargine + glulisine: 0.4 units/kg for BG 140-200 mg/dL; 0.5 units/kg
for BG 201-400 mg/dL (1/2 daily dose given as basal insulin)
SSI = regular insulin 4 times daily for BG > 140 mg/dL
Umpierrez GE et al. Diabetes Care. 2007; 30:2181-6.
Umpierrez GE et al. Diabetes Care. 2011; 34:256-61.
21
Managing Hyperglycemia in Inpatients: Ensuring Success
Example Hypoglycemia Protocol
Essential Part of Insulin Therapy:
Hypoglycemia Protocol
If patient CAN safely swallow
without aspirating
 Clear definition of hypoglycemia
If patient CANNOT safely
swallow or patient has NPO
status
- (BG < 70 mg/dL)
 Nursing order to treat without delay
- Stop insulin infusion (if patient on one - unless type 1
diabetes mellitus)
- Oral glucose (if patient able to take oral)
- IV dextrose or glucagon (if patient unable to take oral)
- Repeat BG monitoring 15 min after treatment for
hypoglycemia and repeat treatment if BG not up to target
- Directions for when and how to restart insulin
If BG 50-69 mg/dL: Give 4
oz. juice or regular soda
If BG 50-69 mg/dL: Give
D50W 25-50 mL (12.5-25
g dextrose) IV push
If BG ≤49 mg/dL: Give 8 oz.
juice or regular soda
If BG ≤ 49 mg/dL: Give 1
mg glucagon IM
• Recheck BG in 15-20 min. If BG <70 mg/dL, then continuously repeat until BG ≥70
mg/dL and notify provider.
• Once BG >70 mg/dL, repeat BG monitoring in 1 hour and check again in 2 hours.
Notify provider of insulin adjustments and changes in BG monitoring.
 Look for cause of hypoglycemia and determine if other
treatment changes are needed
• If BG level has not remained ≥70 mg/dL for both BG checks, notify provider for
further insulin adjustments and changes in BG level monitoring.
Moghissi ES et al. Endocr Pract. 2009; 15:353-69.
Roe ED et al. Hosp Pract (1995). 2012; 40:116-25.
Daily Dose Adjustment
Conclusion
 “Best” blood glucose goal for ICU patients is yet
to be established
 Not All IV insulin protocols are created equal
(regardless of the goal)
 Non-diabetes patients MAY BE different from
patients with diabetes and may benefit from tight
glycemic control
 Large prospective, RCT of non-diabetic patients
following tight glycemic control with multiplication
factor protocol intervention is warranted
 All efforts to reduce hypoglycemia are warranted
• Determine yesterday’s total insulin dose
actually administered
• Review yesterday’s glycemic control
• Calculate today’s scheduled insulin dose
– Some BG values < 90 mg/dL
80% of
yesterday’s total
– BG values 90-179 mg/dL
100% of
yesterday’s total
– Some BG values ≥ 180 mg/dL, no BG < 90
mg/dL
110% of yesterday’s total
McDonnell ME et al. Supplement to ACP Hospitalist.
December 15, 2009: pages 24-30. URL in ref list.
22
Managing Hyperglycemia in Inpatients: Ensuring Success
Leuven I
Leuven II
VISEP
Glucontrol
Sepsis Mixed
ICU
Mixed
NICE SUGAR
Centers
Protocol Heterogeneity
Mixed
1
1
18
19
42
Sample size
1548
1200
488/537
1011
~6030
Diabetic
~13%
~17
~30%
~19%
~20%
Excluded
14
863
1,612
?
34,067
ICU
Stopped early
SICU
MICU
No
No
Yes
Yes
No
Primary diet
TPN 85%
TPN 85%
60% TPN
27% TPN
25% TPN
APACHE II
~9
~23
~20
~15
~21
Mortality
ICU: ~ 7%
Hos: ~10%
ICU: ~25%
Hos: ~40%
28 Day: ~27%
ICU: ~16%
Hos: ~22%
28 Day: ~21%
Hypoglycemia
IIT: 5%
Control: 2%
IIT: 18.7 %
Control: 3.1%
IIT: 17%
Control: 4.1 %
IIT: 9.8
Control: 2.7%
IIT: 6.8 %
Control: 0.5%
Protocol
Leuven
Leuven
Leuven
Variable ?
NICE
Target (mg/dL)
80-110
80-110
80-110
80-110
81-108
144-180
Control (mg/dL)
Timing
Duration
< 180
< 180
< 180
140-180
ICU admit
ICU admit
< 12 hrs
?
< 24 hrs
ICU or 56 days
Eating or 90
days
ICU stay
ICU stay
ICU/ 21 days
IIT = intensive insulin therapy
van den Berghe G et al. N Engl J Med. 2001; 345:1359-67;
van den Berghe G et al. N Engl J Med. 2006; 354:449-61; Brunkhorst FM et al. N Engl J Med. 2008; 358:125-39;
Preiser JC et al. Intensive Care Med. 2009; 35:1738-48; Finfer S et al. N Engl J Med. 2009; 360:1283-97.
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