Transcript Management of Inpatient Hyperglycemia: Facts or Fiction

Management of Inpatient
Hyperglycemia: Review of Recent
Trials and Guidelines
Bruce W. Bode, MD FACE
Atlanta Diabetes Associates
Associate Professor of Medicine
Emory University School of Medicine
Financial Relationships
 Grant/Research Support: Sanofi-Aventis, Lilly
USA, Novo Nordisk
 Consultant: Sanofi-Aventis, Lilly USA, Novo
Nordisk
 Speaker’s Bureau: Sanofi-Aventis, Lilly USA,
Novo Nordisk
 Major Stock Shareholder : Glytec
Diabetes Today: An Epidemic

In 2008, ~26 million Americans
(12% of the population) were diagnosed
with diabetes1

In 2008, 40% of Americans >age 20
have either pre-DM or DM

Complications of diabetes are a major
cause of mortality and morbidity1
 >224,000 deaths
 82,000 lower-limb amputations
 44,000 began treatment for
end-stage kidney disease
 12,000-24,000 new cases of
blindness each year

Total cost in the United States in 2002:
$132 billion1
Hyperglycemia Is Prevalent
at Hospital Admission
38% of all patients at admission have hyperglycemia
– Of those patients, nearly one-third have no history of diabetes
31%
History of diabetes
No history of diabetes
69%
Single-center, retrospective chart review of 1886 patients hospitalized over 15 weeks in a
community teaching hospital. Hyperglycemia defined as BG ≥126 mg/dL on admission or while
fasting, or random BG ≥200 mg/dL on ≥2 occasions.
Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982.
Hospitalizations Account for the Largest Portion of
the Direct Costs of Diabetes Care
2007 Total Direct Cost = $116
billion
Hospitalizations
Nursing home
24%
Office visits
50%
<1%
Outpatient clinics
5%
3%
ER visits
Home health
3%
8%
6%
Hospice
Other (including meds)
American Diabetes Association. Diabetes Care. 2008;31:596-615.
Hyperglycemia: Scope of the Problem
50
Patients, %
40
Diabetes
No Diabetes
50
40
78%
30
30
20
20
10
10
0
0
<110 110-140 140-170 170-200 >200
26%
<110 110-140 140-170 170-200 >200
Mean BG, mg/dL
Kosiborod M, et al. J Am Coll Cardiol. 2007;49(9):1018-183:283A-284A.
Hyperglycemia and Mortality
in the MICU
~3x
Mortality Rate (%)
45
40
~4x
~2x
35
30
25
20
15
10
5
0
80-99
100-119 120-139 140-159 160-179 180-199 200-249 250-299
Mean Glucose Value (mg/dL)
N=1826 ICU patients.
Krinsley JS. Mayo Clin Proc. 2003;78:1471-1478.
>300
Intensive Insulin Management
in Medical-Surgical ICU
P < 0.001
P < 0.002
29.3%
Reduction
Mean BG Levels
(mg/dL)
Baseline group (n = 800)
Hospital
Mortality (%)
Glucose management group (n = 800)
Krinsley JS. Mayo Clin Proc. 79:992-1000, 2004.
Hyperglycemia: A Predictor of Mortality
Following CABG in Diabetics
10
Postop
Mortality
1.8%
P<0.0001
BG >200
n=662
5.0% *
*P<0.001
Adjusted for 19 clinical and operation variables
First Postop Glucose >200
• 2x LOS
• 3x Vent duration
• 7x mortality !!!
CABG, coronary artery bypass graft.
8.6
8
Postop Mortality (%)
BG <200
n=1369
5.8
6
3.8
4
2
1.4
1.7
2.1
0
<150
Furnary AP et al. Circulation. 1999:100 (Suppl I): I-591.
175200225150200
225
250
175
Blood Glucose (mg/dL)
>250
Intensive Insulin Therapy in Critically Ill
Patients: The Leuven SICU Study
Randomized controlled trial: 1548 patients admitted to
a surgical ICU, receiving mechanical ventilation. Patients
were assigned to receive either:
 Conventional therapy: IV insulin only if BG >215 mg/dL
 Target BG levels: 180-200 mg/dL
 Mean daily BG: 153 mg/dL
 Intensive therapy: IV insulin if BG >110 mg/dL
 Target BG levels : 80-110 mg/dL
 Mean daily BG: 103 mg/dL
Van den Berghe et al. N Engl J Med. 2001;345:1359-1367.
Intensive Insulin Therapy in Critically Ill
Patients: SICU
*
*
*
*
*
*
*P<0.01
Van den Berghe et al. N Engl J Med. 2001;345:1359-1367.
Relative Risk Reduction (%)
Benefits of Tight Glycemic Control:
Observational Studies and Early
Intervention Trials
Study
Setting
Population
Clinical Outcome
Furnary, 1999
ICU
DM undergoing open
heart surgery
65%  infection
Furnary, 2003
ICU
DM undergoing CABG
57%  mortality
Krinsley, 2004
Medical/surgical
ICU
Mixed, no Cardiac
29%  mortality
Malmberg, 1995
CCU
Mixed
28%  mortality
After 1 year
Van den Berghe, 2001*
Surgical ICU
Mixed, with CABG
42%  mortality
Lazar, 2004
OR and ICU
CABG and DM
60%  A Fib post op
survival 2 yr
*RCT, randomized clinical trial.
Kitabchi & Umpierrez. Metabolism. 2008;57:116-120.
Medical ICU Study Results
 In-hospital mortality for patients who were in the ICU and on
CII for >3 days was lower (52.5% to 43.0%)
- RRR=18.1%
P=.009
 In-hospital morbidity was lower
- Reduction in newly acquired kidney injury
- Weaning from mechanical ventilation
- Discharge from ICU; discharge from Hospital
 Hypoglycemia was an independent risk factor for mortality
Van den Berghe et al. N Engl J Med. 2006;354:449-461
Tight Glycemic Control Decreased
Morbidity in Medical ICU Patients
Weaning From Mechanical
Ventilation
4.0
4.5
P=.03
3.5
P=.05
P=.04
4
3.5
Intensive
treatment
2.5
3.0
3
2.5
2.0
2.0
Conventional
treatment
1.5
2
1.5
1.0
1.0
0.5
0.5
0
0
0
10
20
30
Discharge From Hospital
5
4.0
3.0
Cumulative hazard
Discharge From ICU
40
50
60 70
80
90
1
0
0
20
40
60
80
100
0
100
200
300
400
500
600
Days after admission to ICU
Prospective, randomized, controlled study of adult patients admitted to the medical ICU, N=1200.
On admission, patients were randomly assigned to intensive treatment or to conventional treatment.
Intensive insulin therapy significantly reduced morbidity but not in-hospital mortality.
Van den Berghe G et al. N Engl J Med. 2006;354:449-461.
14
Intensive Glucose Management in RCT
Trial
N
Setting
Van den Berghe
2006
1200
MICU
HI-5
2006
240
Glucontrol
2007
Primary
Outcome
ARR
RRR
Hospital
mortality
2.7%
7.0%
CCU AMI
6-mo
mortality
-1.8%*
-30%*
1101
ICU
ICU
mortality
-1.5%
Ghandi
2007
399
OR
Composite
VISEP
2008
537
ICU
De La Rosa
2008
504
NICE-SUGAR
2009
6104
*not significant
Odds Ratio
(95% CI)
P-value
0.94*
(0.84-1.06)
NR
N.S.
-10%
1.10*
(0.84-1.44)
N.S.
2%
4.3%
1.0*
(0.8-1.2)
N.S.
28-d
mortality
1.3%
5.0%
N.S.
SICU
MICU
28-d
mortality
-4.2%
0.89*
(0.58-1.38)
NR
ICU
3-mo
mortality
1.14
(1.02-1.28)
< 0.05
*
-13%*
-2.6%
-10.6
N.S.
N.S.
NICE-SUGAR
Trial design: Patients admitted to the ICU were randomized to intensive glucose control
(81-108 mg/dl; n = 3,054) vs. conventional glucose control (<180 mg/dl; n = 3,050). Insulin
was given intravenously and nutrition was given enterally. Mean BG 115 mg vs 144 mg/dL.
Results
(p = 0.02)
30
27.5
(p < 0.001)
24.9
• All-cause mortality at 28 days: 22.3% vs.
20.8% (p = 0.17), respectively
%
• Severe hypoglycemia: 6.8% vs. 0.5% (p <
0.001), respectively
15
6.8
Conclusions
0.5
0
• All-cause mortality at 90 days: 27.5% for
intensive group vs. 24.9% for conventional
group (p = 0.02)
Mortality
All-cause
mortality
at 90 days
Intensive
glucose
control
Severe
hypoglycemia
Severe
hypoglycemia
Conventional
glucose
control
• Among patients admitted to the ICU, intensive
glucose control increased mortality an
absolute 2.6% at 90 days (p = ns; CI 0.4 – 4.8)
• Severe hypoglycemia was more common in
the intensive control group
NICE-SUGAR Investigators. N Engl J
Med 2009;360:1283-97
NICE-SUGAR Study Outcomes
Outcome Measure
Intensive
Group
Conventional
Group
Morning BG (mg/dL)
118 + 25
145 + 26
Hypoglycemia
206/3016
15/3014
(≤ 40mg/dL)
(6.8%)
(0.5%)
28 Day Mortality
(p=0.17)
22.3%
20.8%
90 Day Mortality
(p=0.02)
27.5%
24.9%
The NICE-SUGAR Study Investigators. N Engl J Med. 360:1283-1297, 2009.
NICE-SUGAR: Strengths
1. Large (N=6104)
2. Multicenter
3. Patients characteristic of a general ICU
population
4. Uniformly applied, web-based IV insulin protocol
5. Hard primary endpoint (90-day mortality)
6. Robust analytical plan
NICE-SUGAR: Limitations
1. Specified BG targets & ultimate BG separation
(-27 mg/dl) not as distinct as prior trials
2. Treatment target not achieved in the intensive arm.
3. Variable methods/sources for BG measurement
4. More steroid therapy in intensive arm
5. More hypoglycemia in intensive arm (15-fold)
6. No explanation of increased mortality in intensive
arm (? hypoglycemia)
7. ~ 10% early withdrawls in intensive arm; ‘perprocotol’ (‘completers’) analysis not provided.
Tight Glycemic Control in the Hospital
 By normalizing glucose in the hospital, glucose
toxicity is broken, improving both insulin secretion
and insulin sensitivity
 382 Type 2 DM patients, aged 25–70 years, from
nine hospital centers in China had their glucose
normalized by MDI or CSII for 2 weeks
 Remission rates after 1 year were significantly
higher in the insulin groups (51% in CSII and 44%
in MDI) than in the oral hypoglycaemic agents group
(26%; p=0.0012)
www.thelancet.com Vol 371 May 24, 2008
Intensive Insulin Therapy and Mortality Among
Critically Ill Patients
Favors IIT
Mixed ICU
Medical ICU
Surgical ICU
ALL ICU
Griesdale DE, et al. CMAJ. 2009;180(8):821-827.
Favors Control
Intensive Insulin Therapy and Hypoglycemic
Events in Critically Ill Patients
No. Events/Total No. Patients
Study
IIT
Control
Risk ratio (95% CI)
Van den Berghe et al
Henderson et al
Bland et al
Van den Berghe et al
Mitchell et al
Azevedo et al
De La Rosa et al
Devos et al
Oksanen et al
Brunkhorst et al
Iapichino et al
Arabi et al
Mackenzie et al
NICE-SUGAR
39/765
7/32
1/5
111/595
5/35
27/168
21/254
54/550
7/39
42/247
8/45
76/266
50/121
206/3016
654/6138
6/783
1/35
1/5
19/605
0/35
6/169
2/250
15/551
1/51
12/290
3/45
8/257
9/119
15/3014
98/6209
6.65 (2.83-15.62)
7.66 (1.00-58.86)
1.00 (0.08-11.93)
5.94 (3.70-9.54)
11.00 (0.63-191.69)
4.53 (1.92-10.68)
10.33 (2.45-43.61)
3.61(2.06-6.31)
9.15 (1.17-71.35)
4.11(2.2-7.63)
2.67 (0.76-9.41)
9.18 (4.52-18.63)
5.46 (2.82-10.60)
13.72 (8.15-23.12)
Overall
Hypoglycemic Events
Favors IIT
Favors Control
5.99 (4.47-8.03)
Reproduced with permission from Griesdale DE, et
al. CMAJ. 2009;180(8):821-827.
0.1
1
10
Risk Ratio (95% CI)
Is Hypoglycemia Life Threatening?
Strategies for Preventing Hypoglycemia
Blood Glucose During Hospitalization
and Incidence of Death Within 2 Years
Lowest blood glucose recorded during hospital stay
≤3.0 mmol/L or 55 mg/dL
n+44; 20 deaths
3.1-6.5 mmol/L or 56-119 mg/dL
n=364; 101 deaths
1.93
(1.18-3.17)
Referent
≥6.6 mmol/L or ≥120 mg/dL
n=276; 107 deaths
1.48
-3.5
-2.5
-1.5
-.5
.5
Svensson AM et al. Eur Heart J. 2005 26:1255-1261.
1.5
(1.09-1.99)
2.5
3.5
Severe Hypoglycemia in Critically Ill Patients
Associated With Increased Risk of Mortality
Mortality Rate, %
60
50
40
30
20
10
0
SH
Controls
No SH
Severe hypoglycemia (<40 mg/dL) was associated with an
increased risk of mortality (OR, 2.28; 95% CI, 1.41-3.70; P=.0008)
Krinsley JS, Grover A. Crit Care Med. 2007;35(10):2262-2267.
Blood Glucose & Post-AMI Outcomes
A U-Shaped Relationship?
20
Death
Endpoint at 30 days (%)
18
Death or recurrent MI
P < 0.001 for each endpoint
16
Death, recurrent MI or CHF
13.0
14
12
10.3
10
8.0
8
6
10.2
10.0
4.6
4.1
5.0
5.0
6.0
1.0
2
5.2
3.9
4
1.6
6.3
5.8
4.7
2.4
0
< 81
81 – 99
100 – 125
126 – 149
Blood glucose level (mg/dL)
Pinto DS, et al. J Am Coll Cardiol. 2005;46:178-180.
150 – 199
> 199
Mean Glucose & In-Hospital Mortality
in 16,871 Patients with AMI
(Reference: Mean BG 100-110 mg/dl)
Kosiborod M et al. Circulation 2008:117:1018
Hypoglycemia and Cardiovascular
Events
 Tachycardia and high blood pressure
 Myocardial ischemia
 Silent ischemia, angina, infarction
 Cardiac arrhythmias
 Transiently prolonged corrected QT interval,
 Increased QT dispersion
 Sudden death
Wright RJ, Frier BM, Diabetes Metab Res Rev 2008; 24: 353–363.
Strategies for Preventing
Hypoglycemia in the ICU
• Better protocols and systems to implement insulin
protocols
• Less aggressive BG targets (AACE/ADA Guidelines)
• Improved glucose monitoring devices to analyzed
frequent and accurate real-time CGM
• Inpatient hyperglycemia teams
AACE/ADA Recommended Target
Glucose Levels in ICU Patients
 ICU setting:
 Starting threshold of no higher than 180 mg/dL
 Once IV insulin is started, the glucose level should be
maintained between 140 and 180 mg/dL
 Lower glucose targets (110-140 mg/dL) may be appropriate
in selected patients
 Targets <110 mg/dL or >180 mg/dL are not recommended
Not recommended
<110
Acceptable
110-140
Recommended Not recommended
140-180
>180
Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).
http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.
AACE/ADA Target Glucose Levels
in Non–ICU Patients
 Non–ICU setting:
 Premeal glucose targets <140 mg/dL
 Random BG <180 mg/dL
 To avoid hypoglycemia, reassess insulin regimen if
BG levels fall below 100 mg/dL
 Occasional patients may be maintained with a glucose
range below and/or above these cut-points
Hypoglycemia = BG <70 mg/dL
Severe hypoglycemia = BG <40 mg/dL
Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).
http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf
Methods For Managing Hospitalized
Persons with Diabetes
Continuous Variable Rate IV Insulin Drip
Surgery, NPO, Unstable, MI, DKA,
Hyperglycemia, Steroids, Gastroparesis,
Delivery, etc
Basal / Bolus Therapy (MDI) when
eating
The Ideal IV Insulin Protocol
Easily ordered (signature only or
preferably nurse mandated)
Effective (Gets to goal quickly)
Safe (Minimal risk of hypoglycemia)
Easily implemented
Able to be used hospital wide
Essentials of a good IV Insulin Algorithm
Easily implemented by nursing staff
Able to seek BG range via:
- Hourly BG monitoring
- Adjusts to the insulin sensitivity
of the patient
Various Protocols Exist
 Atlanta Multiplier Method
 Van den Berghe (studied in critical care
setting)
 Portland Protocol (used in surgical setting)
 Markovitz (studied in postoperative heart
surgery patients)
 Yale Protocol (studied in medical intensive care
setting)
Practical Closed Loop Insulin Delivery: Multiplier Method
A System for the Maintenance of Overnight Euglycemia and the
Calculation of Basal Insulin Requirements in Insulin-Dependent
Diabetics
1/slope = Multiplier = 0.02
6
5
4
Insulin Rate (U/hr)
3
2
1
0
0
100
200
300
Glucose (mg/dl)
NEIL H. WHITE, M.D., DONALD SKOR, M.D., JULIO V. SANTIAGO,
M.D.;Ann Int Med 1982 ;97:210-214
400
Continuous Variable Rate IV Insulin Drip
Atlanta Multiplier Method
 Starting Rate Units / hour = (BG – 60) x 0.02
where BG is current Blood Glucose
and 0.02 is the multiplier
 Check glucose every hour and adjust drip
 Adjust Multiplier to keep in desired glucose
target range (90 to 120 in ICU; 100 to 140 on
floor)
Multiplier
Principles
10
9
8
7
Insulin 6
Units / Hour 5
4
3
2
1
0
0
100
200
300
Glucose
mg/ dl
Davidson et al, Diabetes Care 28(10): 2418-2423, 2005
400
500
INSULIN IV INFUSION FOR TARGET 80-110MG/DL
(Nurse Calculated)
Patient Name_____________________________ ID#__________________ Date____________
IV insulin infusion rate (units of insulin/hour) = (BG-60) x (multiplier)
1) Obtain initial BG per hospital, standardized meter
2) Initiate IV insulin drip by applying the current BG and the multiplier 0.02 to the above formula
3) If current BG is greater than 110 and has not dropped at least 15% (see Figure 1) over previous BG,
increase the Multiplier by 0.01
4) If current BG is greater than 110 and has dropped at least 15% (see Figure 1) over previous BG,
use the same Multiplier
5) If BG 80-110, do not change the multiplier but continue adjusting the drip rate according to the formula
6) If BG less than 80 refer to the hypoglycemia algorithm (Figure 2) shown below
(Figure No. 2)
(FIGURE No. 1)
Hypoglycemia Dosing Algorithm
15% DROP IN BLOOD GLUCOSE
BG
Previous BG
451-475
385-450
334-384
290-333
251-289
217-250
188-216
163-187
141-162
121-140
Time
BG
Current BG
Less than 405
Less than 355
Less than 305
Less than 265
Less than 230
Less than 200
Less than 175
Less than 155
Less than 135
Less than 120
Multiplier
Based on formula: (100-BG) x (0.4) = ml D50 IV push
ACTION
D50W
Action
DO
71-79
10 ml IV push
NOT
60-69
15 ml IV push
50-59
20 ml IV push
30-49
25 ml IV push
Under 30
30 ml IV push
CHANGE
MULTIPLIERS
Drip Rate
ml/hr = units/hr
Nurse’s Signature
* Decrease multiplier by 0.01
* Recheck BG in 15 minutes
* Repeat as necessary
* Decrease multiplier by 0.01
* Recheck BG in 15 minutes
* Repeat as necessary
* Contact Physician if BG < 60 for
2 consecutive BG measurements
Notes/Other
(Document all D50W corrections)
(FIGURE No. 1)
TARGET BG 80-110 (1 ml = 1 unit)
DIRECTIONS:
Start infusion using
the drip rate (ml/hr)
in COLUMN No.2
for the current
Blood Glucose Tier
Blood
Glucose
Tiers
To determine the new
drip rate, compare the
current BG Tier to the
previous BG Tier.
Over 450
If current BG Tier is
lower than the
previous BG Tier,
STAY IN THE
SAME COLUMN
If current BG Tier has
not dropped (is the
same or higher),
MOVE 1 COLUMN
TO THE RIGHT
If more than 16
columns are needed:
Refer to page No. 2
When hourly BG is
80-110, stay in the
same column to
determine the new
drip rate.
Do Not Change
Columns
When new BG is
less than 80, Move
1 Column To
The Left and
refer to Figure no. 2
for D50 treatment.
The Column Dosing Chart is the property of the Georgia Hospital
Association’s Diabetes SIG: All Rights Reserved; Copyright Pending
column
column
column
column
column
column
column
column
column
column
column
column
column
column
column
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
column
16
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/Hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
(ml/hr)
4.4
3.6
3
2.5
2.1
1.7
1.4
1.2
1
0.8
0.6
0.5
0.4
0.4
0.3
0.3
0.2
0.2
0.1
0.1
0
8.8
7.2
6
5
4.2
3.4
2.8
2.4
2
1.6
1.2
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0
13.2
10.8
9
7.5
6.3
5.1
4.2
3.6
3
2.4
1.8
1.5
1.3
1.2
1
0.9
0.7
0.6
0.4
0.3
0
17.6
14.4
12
10
8.4
7.2
5.6
4.8
4
3.2
2.4
2
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0
22
18
15
12.5
10.5
8.5
7
6
5
4
3
2.5
2.2
2
1.7
1.5
1.2
1
0.7
0.5
0
26.4
21.6
18
15
12.6
10.2
8.4
7.2
6
4.8
3.6
3
2.7
2.4
2.1
1.8
1.5
1.2
0.9
0.6
0
30.8
25.2
21
17.5
14.7
11.9
9.8
8.4
7
5.6
4.2
3.5
3.1
2.8
2.4
2.1
1.7
1.4
1
0.7
0
35.2
28.8
24
20
16.8
13.6
11.2
9.6
8
6.4
4.8
4
3.6
3.2
2.8
2.4
2
1.6
1.2
0.8
0
39.6
32.4
27
22.5
18.9
15.3
12.6
10.8
9
7.2
5.4
4.5
4
3.6
3.2
2.7
2.3
1.8
1.3
0.9
0
44
36
30
25
21
17
14
12
10
8
6
5
4.5
4
3.5
3
2.5
2
1.5
1
0
48.4
39.6
33
27.5
23.1
18.7
15.4
13.2
11
8.8
6.6
5.5
5
4.4
3.8
3.3
2.7
2.2
1.7
1.1
0
52.8
43.2
36
30
25.2
20.4
16.8
14.4
12
9.6
7.2
6
5.4
4.8
4.2
3.6
3
2.4
1.8
1.2
0
57.2
46.8
39
32.5
27.3
22.1
18.2
15.6
13
10.4
7.8
6.5
5.8
5.2
4.6
3.9
3.2
2.6
1.9
1.3
0
61.6
50.4
42
35
29.4
23.8
19.6
16.8
14
11.2
8.4
7
6.3
5.6
4.9
4.2
3.5
2.8
2.1
1.4
0
66
54
45
37.5
31.5
25.5
21
18
15
12
9
7.5
6.7
6
5.3
4.5
3.7
3
2.2
1.5
0
70.4
57.6
48
40
33.6
27.2
22.4
19.2
16
12.8
9.6
8
7.2
6.4
5.6
4.8
4
3.2
2.4
1.6
0
(mg/dl)
385-450
334-384
290-333
251-289
217-250
188-216
163-187
141-162
121-140
111-120
106-110
101-105
96-100
91-95
86-90
80-85
75-79
71-74
60-70
Under 60
(Figure No.2)
BG
70-79
60-69
D50W
10 ml IV Push
15 ml IV Push
50-59
30-49
Under 30
20 ml IV Push
25 ml IV Push
30 ml IV Push
*
*
*
*
*
*
*
ACTION
If you have not moved 1 column to the left as directed above, do so now
Recheck BG in 15 minutes
Repeat as necessary
If you have not moved 1 column to the left as directed above, do so now
Recheck BG in 15 minutes
Repeat as necessary
Contact physician if BG is under 60 for 2 consecutive BG measurements
(Figure No. 3)
*
*
*
*
*
NOTIFY PHYSICIAN IF:
BG is less than 60 for 2 consecutive BG measurements
BG reverts to greater than 200 for 2 consecutive BG measurements
If an insulin requirement exceeding 24 units/hour does not result in a
lower BG Level or if the drip rate (ml/hr) drops to less than 0.5 units/hr
If the K+ level drops to less than 4
If continuous enteral feeding, TPN, or IV insulin infusion is stopped
Ideal Solution
 Computer directed insulin infusion
 Complexity is moved to the computer
 Standardization is achieved
 Hypoglycemia is minimized
Davidson et al, Diabetes Care 28(10): 2418-2423, 2005
Computer-Guided Vs. Standard ColumnBased Insulin Regimens
Study Aim: To determine differences in glycemic
control between treatment with a computer-guided
algorithm (Glucommander) and a standard paperform algorithm in critically ill patients in the ICU
Design: Multi-center, prospective, randomized trial in
hyperglycemic patients admitted to a medical ICU
Primary outcome: Differences in BG control
Secondary outcomes: Number of hypoglycemic (BG
<60 mg/dL and < 40 mg/dl) and hyperglycemic events
(BG >200 mg/dL), ICU and hospital length of stay
Newton CA et al. Diabetes 57 (Suppl. 1) 136A, 2008.
Glucommander vs. Standard
Mean Glucose Values
Mean Glucose Maintained once Target Achieved
Glucommander = 103.4 ± 9 mg/dL
Standard = 120.4 ± 18 mg/dL
Newton CA et al. Diabetes 57 (Suppl. 1) 136A, 2008.
* p < 0.0001
Glucommander vs. Standard
% of Glucoses Maintained within Target Achieved
Glucommander = 68.6%
Standard = 46.4%*
Newton CA et al. Diabetes 57 (Suppl. 1) 136A, 2008.
* p < 0.0001
% of PATIENTS with LOWEST BG < 40 mg/dL
N
BGmean
523
194
1200
111
537
112
504
*
3034
118
1548
103
79
102
2911
107
3095
121
370
102
30%
25%
20%
All GlucommanderTM
1.1%
18%
17%
NICE-SUGAR
0.27%
U
0%
IC
+
G
G
A
Le
R
uv
en
SI
C
U
M
ed
IC
U
IC
N
D
e
La
ESU
R
os
a
EP
VI
S
A
ra
Le
bi
uv
en
M
IC
U
Other Tight-Control
0.3%
2%
Su
rg
2.9%
0%
U
5.2%
+S
IC
6.8%
G
9%
4
5%
n
10%
28.6%
Ve
rs
io
15%
GlucommanderTM
Strategies for Preventing Hypoglycemia
Algorithm 1
Algorithm 2
BG (mg/dL) Units/hr
BG
(mg/dL)
Algorithm 3
Units/hr
BG
(mg/dL)
Algorithm 4
Units/hr
BG
(mg/dL)
Units/hr
<60 = Hypoglycemia (See below for treatment)
<70
Off
<70
Off
<70
Off
<70
Off
70-109
0.2
70-109
0.5
70-109
1
70-109
1.5
110-119
0.5
110-119
1
110-119
2
110-119
3
120-149
1
120-149
1.5
120-149
3
120-149
5
150-179
1.5
150-179
150-179
7
180-209
2
180-209
9
210-239
2
210-239
12
240-269
3
240-269
16
270-299
3
270-299
20
300-329
4
300-329
24
330-359
4
330-359
8
330-359
14
>360
6
>360
12
>360
16
2
150-179
Reduce
insulin 4
180-209
3
180-209
5
or hold
insulin6
210-239rate 4
210-239
240-269
5
240-269
infusion
at a 8
270-299
6
270-299
10
higher
BG 12
300-329
7
300-329
concentration
Newton CA et al. Diabetes 57 (Suppl. 1) 136A, 2008.
>330
28
Events Triggering Hospital Hypoglycemia
 Transportation off ward, causing meal delay
 Failure to measure blood glucose before insulin doses
 New NPO status
 Interruption of




IV dextrose therapy
Total parenteral nutrition
Enteral feedings
Continuous venovenous hemodialysis
Braithwaite SS, et al. Endocr Pract. 2004;10(suppl 2):89-99.
Features Increasing the Risk of
Hypoglycemia in an Inpatient Setting
 Advanced age
 Renal failure
 Liver disease
 Concurrent illness (cerebral vascular accident,
congestive heart failure, shock, sepsis)
 Ventilator use
 Concurrent medications (-blockers, quinolones,
epinephrine)
D’Hondt NJ. Diabetes Spectrum. 2008;21(4):255-261.
Benefits of a
Nurse-Mandated Protocol
 All patients are screened and treated the
same way
 Standardization can be achieved
 Modification of the protocols can easily
be done based on outcomes and analysis
of the data
Patient Presents With
Hyperglycemia
Previously diagnosed DM
Diabetic ketoacidosis or
hyperglycemic crisis follow
DKA protocol
Modification of therapy to
keep BG at goal
No previous diagnosis of DM
and BG
> 140 mg/dL
Begin BG testing
BG is > 110 mg/dL for a
critically ill patient; notify
physician for initiation of IV
insulin therapy
All patients with hyperglycemia
should have an HbA1C drawn
to aid in transition and discharge therapy
BG is > 140 mg/dL for
noncritically ill patient, notify
physician for initiation of
subcutaneous therapy
Methods of Screening for Hyperglycemia
 Finger stick blood glucose on admission or use of
the glucose done on the biochemical profile
 If glucose >110 mg/dL fasting or >140 mg/dL random,
place in appropriate protocol and continue
monitoring
 Draw Hemoglobin A1C for help in deciding who
needs transition from IV to SC insulin and what
treatment is needed at home, including insulin.
Glycemic Control Orders
NURSING

Height and measured Weight (populated from nursing flow sheet )

Blood Glucose per fingerstick on admission to nursing unit
If Blood Glucose greater the 140 mg/dL → Bedside blood glucose monitoring
AC, HS and 3am
If no DM history and no Blood Glucose is greater than 140 mg/dL again in the
next 24 hours, discontinue BG checks


LABARATORY

If Blood Glucose greater than 140 mg/dL or history of diabetes, draw HbA1c
INSULIN
If BG greater than 140 mg/dL, give rapid acting correction insulin per formula:
(BG – 100)/40 = # units Rapid Acting Insulin SC
 If blood glucose greater than 140 mg/dL x 2 in 24 hours, begin weight based
basal/bolus insulin per formula: weight in kilograms x 0.5 = Total Daily Insulin
Dose. Give 50 % as basal Lantus insulin SC at HS and 50% as Rapid Acting
Insulin bolus insulin divided into 3 equal pre-meal doses with correction dose
(computer calculated).
NOTE: MD TO CHECK BG VALUES DAILY for INSULIN DOSE ADJUSTMENTS
 Insulin as ordered (opens the simplified list of insulins appearing in descending
order with the most commonly ordered appearing first).
 Call MD for IV insulin orders (per Glucommander protocol) if patient scheduled

(computer calculated).
NOTE: MD TO CHECK BG VALUES DAILY for INSULIN DOSE ADJUSTMENTS
 Insulin as ordered (opens the simplified list of insulins appearing in descending
order with the most commonly ordered appearing first).
 Call MD for IV insulin orders (per Glucommander protocol) if patient scheduled
for surgery within 24 hours, NPO, or unable to eat.
 If HgA1c greater than 7, discharge home on insulin
 Insulin per patient’s Insulin Pump according to hospital insulin pump protocol
HYPOGLYCEMIA
Per hospital protocol: if BG <60 mg/dL, ml of D50 IV push = (100 – BG mg/dL) x 0.4
DIETARY
 1800 calorie ADA diet
 Other diet
 Nutrition consult
CONSULTS
Endocrine/Diabetes consult if HbA1c greater than 7 or new to insulin or DKA or
major hypoglycemia (Coma or Seizure) or if
 If new diagnosis of diabetes or new to insulin, Diabetes consult
New diagnosis yes
no
New to insulin yes
no
□ Consult to Diabetes Education Center if on Insulin Pump

DRCShrDataGlyControlRev110707
Results of Nurse-Mandated
Protocol in CV Patients
 ~2000 CV surgery patients have been studied
 On IV insulin BG stabilized at <120 mg/dL in a mean
of 3 hours
 IV insulin was continued for an average of 37 hours
 98% were controlled so that no BG was >200 mg/dL
in the 48 hours following surgery
 2% had transient BG <50 mg/dL; 0% <40 mg/dL
 The mean for all BG in all patients was 107 mg/dL
Davidson PC et al. J Diabetes Sci and Technol. 2008; 2(3):369-375.
Average BG’s ± SD of All Glycemic
Protocol Runs (n = 470)
200
Blood glucose (mg/dL)
180
160
140
120
100
80
60
0
5
10
15
Hours on Glucommander
20
25
Transition to SubQ
Managed by Anesthesiology
in Operating Room
SubQ Basal-Bolus
Glucommander
0
12
24
hours
36
48
60
Transition from Glucommander to Basal-Bolus
Insulin
Glargine and Aspart
Basal: Multiplier * 500; CIR: 0.5 / Multiplier; Correction Factor: 1.7 / Multiplier
220
180
n=209
160
140
120
100
80
60
Hours after IV insulin
Breakfast
72
3:00AM
64
Bedtime
Dinner
56
Lunch
Breakfast
48
3:00AM
40
Bedtime
32
Lunch
Breakfast
24
3:00AM
16
Bedtime
Dinner
8
Lunch
0
Dinner
40
Last GM
Blood Glucose (mg/dl)
200
CVS Hyperglycemia Protocol
Piedmont Hospital 2006
 Reduced post-op length of stay: 0.8 days
 ICU cost per day: $1,244.99
 CVS at Piedmont per year: 998
 Annual savings: 0.8 * $1,245 * 998 = $994,000
 Sites in database of Society of Thoracic Surgeons:
860
 Projected total national savings: $855 million
Converting to SC insulin
 If More than 0.5 u/hr IV insulin required with normal
BG, start long-acting insulin (glargine)
Exception: if no prior DM and normal A1C, may
not need SC insulin
 Must start SC insulin at least 1 to 2 hours before
stopping IV insulin
 Some centers start long-acting insulin on initiation
of IV insulin or the night before stopping the drip
Intravenous Insulin Infusion Under Basal
Conditions Correlates Well With Subsequent
Subcutaneous Insulin Requirement
Total Intravenous vs. Subcutaneous 24-hour
Insulin Requirements, units
Units
SQ
275
250
225
200
175
150
125
100
75
50
25
0
0
25 50 75 100 125 150 175 200 225 250 275
Units IV
Hawkins et al. Endocr Pract. 1995;1:385–389.
Basal/Bolus Treatment Program with
Rapid-acting and Long-acting Analogs
Plasma insulin
Breakfast
4:00
Lunch
Dinner
Aspart, Aspart,
Lispro Lispro
or
Aspart,
Lispro
or
or
Glulisine Glulisine
Glulisine
Glargine
or
Detemir
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
Converting from IV to SC insulin
 Establish 24 hr Insulin Requirement
– Extrapolate from average over last 4 hr if stable
 Give One-Half Amount As Basal
 Give One-Half Amount As Total Bolus
– Give post meal based on portion of food consumed
or
– Give 1.5 units Rapid-acting for every CHO consumed
 Monitor a.c. tid, hs, and 3 am
 Correction Bolus for All BG >140 mg/dl
Initiating SC Basal Bolus
 Starting total dose = 0.5 x wgt. in kg
Wt. is 100 kg; 0.5 x 100 = 50 units
 Basal dose (glargine) = 50% of starting dose at HS
0.5 x 50 = 25 units at HS
 Bolus doses (rapid analog) = 50% of starting dose
0.5 x 50 = 25 divided by 3 = ~8 units pc (tid)
 Correction bolus = (BG - 100)/ CF, where
CF = 1700/total daily dose; CF = 30
Case #1
 Fifty-eight y/o male with:
– Shortness of breath lasting ~48 hours
– Substernal fullness (oppressive feeling) OFF/ON for 4
 T2DMhours
x 8 years
 Metformin plus SU plus TZD (maximum doses)
 CAD with history of MI 3 years ago
 2 vessel stent placements following MI
 Dual oral antiplatelet therapy
 HTN x 8 years
 ACE inhibitor, β-blocker, furosemide
 Dyslipidemia x 8 years
 Statin
SU, 64
sulfonylurea; TZD, thiazolidinedione; CAD, coronary artery disease; HTN, hypertension; ACE, angiotensin
converting enzyme; BMI, body mass index.
BG, mg/dL
Rabbit 2 Trial: Treatment Success With
Basal-Bolus vs. Sliding Scale Insulin
300
280
260
240
220
200
180
160
140
120
100
Sliding-scale
Basal-bolus
Hypoglycemia rate:
 Basal Bolus Group:
 BG < 60 mg/dL: 3%
 BG < 40 mg/dL: none
Admit 1
2
3 4 1 2 3 4
Days of Therapy
5
6
7
Persistent hyperglycemia (BG>240 mg/dl)
is common (15%) during SSI therapy
Umpierrez GE, et al. Diabetes Care. 2007;30(9):2181-2186.
 SSRI:
 BG < 60 mg/dL: 3%
 BG < 40 mg/dL: none
Rabbit 2 Trial: Changes in Glucose Levels With
Basal-Bolus vs. Sliding Scale Insulin
240
220
BG, mg/dL
a
200
a
a
b
180
b
b
b
Sliding-scale
160
140
Basal-bolus
120
100
Admit
aP<.05.
1
2
3
4
5
6
7
8
9
10
Days of Therapy
bP<.05.
• Sliding scale regular insulin (SSRI) was given 4 times daily
• Basal-bolus regimen: glargine was given once daily; glulisine was given before meals.
0.4 U/kg/d x BG between 140-200 mg/dL
0.5 U/kg/d x BG between 201-400 mg/dL
Umpierrez GE, et al. Diabetes Care. 2007;30(9):2181-2186.
Correction Bolus Formula
Current BG - Ideal BG
Glucose Correction factor
Example:
–Current BG:
–Ideal BG:
250 mg/dl
100 mg/dl
–Glucose Correction Factor: 30 mg/dl
250 - 100
= 5.0u
30
4. CORRECTION DOSE INSULIN TYPE:
 Rapid Acting Analog
 Regular Insulin
[ ] Low Dose Algorithm (for thin, elderly, or renal patients) [Blood Glucose (BG) – 100 / 50]
BG ac, hs, 0300h
141-175
176-225
226-275
276-325
326-375
If greater than 375
Additional Insulin
1 unit
2 units
3 units
4 units
5 units
Contact M.D.
[ ] Moderate Dose Algorithm (for average size adult) [BG – 100/ 40]
BG ac, hs, 0300h
141-160
161-200
201-240
241-280
281-320
If great than 320
Additional Insulin
1 unit
2 units
3 units
4 units
5 units
Contact M.D.
[ ] Moderate High Dose Algorithm (for obese or infected patients or those on steroids) [BG-100/30]
BG ac, hs, 0300h
141-145
146-175
176-205
206-235
236-265
296-325
If greater than 326
Additional Insulin
1 unit
2 units
3 units
4 units
5 units
7 units
Contact M.D.
[ ] High Dose Algorithm (for very insulin resistant patients or septic patients) [BG-100/20]
BG ac, hs, 0300h
141- 150
151-170
171-190
191-210
211-230
231-250
251-270
271-290
If greater than 291
Additional Insulin
2 units
3 units
4 units
5 units
6 units
7 units
8 units
9 units
Contact M.D.
*If above correction is not working and BG is persistently >140 mg/dl, consider using an individualized
correction dose algorithm with calculations.
[ ] Calculate the Individualized Correction Dose for BG > 140 mg/dl, using the formula:
Categories of “Never” Events
 Surgical





eg, Amputation of incorrect body part
Product/device
eg, Use of contaminated device
Patient protection
eg, Inability to prevent a patient suicide
Care management
eg, Medication error leading to hypoglycemic
event
Environmental
eg, Patient fall during hospital stay
Criminal
eg, Impersonation of a health care provider
69
National Quality Forum. Serious Reportable Events in Healthcare, 2006 Update: Executive Summary. Washington, DC: NQF; 2007.
Protocol for Treatment of
Hypoglycemia
 Any BG <60 mg/dl: D50 = (100-BG) x 0.4 ml IV
 Recheck in 15 minutes and retreat if needed
 If eating, may use 15 gm of rapid CHO
 Do Not Hold Insulin When BG Normal
Hospital-Acquired Conditions:
“Reasonably Preventable” Events
Foreign object left in
patient postsurgery
Air embolism
Blood incompatibility
Falls and trauma
Pressure ulcers
Vascular catheterrelated infection
Catheter-related urinary
tract infection
Manifestations of poor
glycemic control
Certain orthopedic surgical
site infections
Surgical site infectionmediastinitis following CABG
Bariatric surgical site infections
Deep vein thrombosis or
pulmonary embolism after
orthopedic procedures
Department of Health and Human Services: Centers for Medicare and Medicaid Services. Fed Regist. 2008;73:48433-49084.
TPN or Enteral Feedings
 Determine insulin requirement via IV Insulin
needs
 For TPN, add insulin to TPN bag with correction
SC every 4 to 6 hours
 For enteral feedings, give Glargine or Detemir
every 12 hours or NPH every 8 hours or Regular
every 6 hours with correction SC every 4 to 6
hours.
Hospital Diabetes Plan
What Can We Do For Patients Admitted To
Hospital?
 Pathway Protocols For All Hyperglycemia and
Diabetes Patients
 Finger Stick BG ac qid on ALL Admissions with
BG >140 mg/dL or history of DM or high risk
(ICU, Cardiac, Vascular, CVA, Steroids, etc)
 Check Hemoglobin A1C in all hyperglycemic
patients
Hospital Diabetes Plan
Protocol for Insulin in Hospitalized
Patient
 Treat Any Patient With BG >110 or >140 mg/dl
With Insulin
– If able to eat and not acutely sick, initiate
basal bolus therapy SC
– If unable to eat or acutely ill or unable to
control, pace on an insulin drip
 If known diabetes or A1c >6%, transition
patient to basal bolus therapy once BG at goal
and stable.
Endocrine or Diabetes Consult
 Endocrine/Diabetes consult for any of the
following reasons:
- Glycemic control is not obtained
(i.e. BG’s <70 or >140 mg/dl)
- At the request of nursing services
- At MD request
Diabetes Education and Discharge
Planning
 Diabetes service is contacted for all patients
new to SC insulin.
 Discharge planning is initiated.
 Instruct Patient in Monitoring and Recording
See That Patient Has Meter on Discharge
 Decide on Case Specific Program for
Discharge
 Arrange Early F/U with PCP
Conclusion
 Our journey is not over, it has only begun
 We must normalize glucose in all hospital
patients
 By implementing, assessing, and revising
protocols / pathways for hyperglycemic
management, we can ultimately achieve
this goal of euglycemia