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Tight Glycemic Control:
Implementation, the key to success
Vinay Vaidya, MD
-Assistant Professor Pediatrics
-Director, Pediatric Critical Care Fellowship Program
University of Maryland School of Medicine
Some questions
• How common is Diabetes / Hyperglycemia in
hospitalized patient ?
• Is Hyperglycemia Bad?
• Is Normoglycemia Good?
• What’s the pathophysiologic basis?
• How is Tight Glycemic Control (TGC) achieved ?
• What’s going on in ICU’s at UMMS?
• Challenges in implementing TGC?
• What’s going on in the PICU?
• Anesthesia implications ?
• Future directions?
2
Diabetes is common in Hospitals
• 9.5% of all hospital discharges, fourth most
common co-morbid diagnosis in all discharges.
• 29% of cardiac surgery patients
• 2-4 fold increase in rates of hospitalizations
• Increases length of stay by 1-3 days
3
Incidence of Hyperglycemia in
ICU’s
• More than 80 to 90% of ICU patients will
have a blood sugar > 126 mg/dl and
approximately 60% will NOT BE KNOW
DIABETICS
• 98.7% of 1548 patients BS > 110 mg/dl
(Van den Berghe study, 2001)
4
Is Hyperglycemia bad?
5
Not really!
by Conventional logic …
• Physiologically stress = Hyperglycemia
• Hyperglycemia = Marker of illness severity
• Not implicated in directly contributing to
morbidity & mortality
• Largely ignored & untreated unless
BS > ? 200 mg/dl
6
Let’s look at the evidence ..
7
Hyperglycemia in
hospitalized pts
Umpierrez et al J Clin Endocrinol Metab 2002
• 2030 patients on general floor
• Prevalence: 38%
• 10 fold increased mortality (16% vs
1.7%) if BS > 126 mg/dl
• 2 fold Length of Stay
• Higher admission to ICU
• Increased infection risk 8
Hyperglycemia & Acute MI
Capes et al. Lancet. 2000
• Meta-analysis of 15 studies (BG >110
mg/dL with or without a prior diagnosis of
diabetes
• increased in-hospital mortality
• Increased CHF
9
Hyperglycemia in Cardiac
Surgery Patients
Furnary, Circulation 1999
Zerr, Ann Thorac Surg 1997
• Hyperglycemia associated with
increased
– mortality
– deep wound infections
– overall infection
• Hyperglycemia, on postop day 1 & 2 =
single most important predictor of
serious infectious complications.
10
Hyperglycemia & Stroke
Capes et al, Stroke 2001
Kiers et al, J Neuro Neurosurg Psych 1992
• Meta-analysis of 26 studies on stroke: Increased
mortality levels in non-diabetics with
hyperglycemia
• Stroke survivors: BS range 120-145 mg/dl:
Worse functional recovery.
• Patients with known diabetes and/or newly-
discovered hyperglycemia (>140 mg/dl) more
severe strokes with greater mortality
11
High BS is Bad, Is Higher Bader?
Krinsley, Mayo Clinic Proceedings, 2003
• 1,826 ICU patients
• direct and proportional correlation with BS
• BS range from < 100 to > 300: Mortality
10% to 43%
• Even modest hyperglycemia associated
with a substantial increase in mortality in
patients with a wide range of medical and
surgical diagnoses
12
Pregnancy & Hyperglycemia
• It is well-known that pregnancy
complicated by uncontrolled diabetes
results in poor fetal outcomes
13
Pediatric evidence …1
• 50% of 353 critically ill children had initial
glucose >120 mg/dL ()
– Ruiz Magro P, et al [Metabolic changes in critically ill children]. An
Esp Pediatr 1999;51:143-8
14
Pediatric evidence …2 Hyperglycemia
(>126 mg/dl)
Very
Common:
86%
MORTALITY
Higher peak &
longer duration
of
Hyperglycemia
in Non-survivors
15
Pediatric evidence …3
5.7 times
more likely
to DIE
Hyperglycemia for highest BS >
(>120 mg/dl) 120 mg/dl in first
10 days
Very
Common:
75%
16
Yes,
Hyperglycemia =
17
If HYPERGLYCEMIA
is bad …
Is NORMOGLYCEMIA
good? 18
The Case for Normglycemia /
Tight Glyemic control (TGC)
19
1921–Face of Insulin
Millions of diabetic lives saved .. 20
Face of Insulin: today
? Millions of Non-
diabetic lives too ? 21
DIGAMI trial
Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction
Malmberg et al Circulation. 1999
• 620 diabetic patients with acute MI
• 306 randomly assigned patients to
intensive insulin therapy &
• 314 to routine antidiabetic
• 3.5 year follow-up
• significantly reduced long-term mortality
(33% vs. 44%)
22
2001
23
• 1548 Surgical ICU pts
• TREATMENT GROUP:
– target 80 to 110 mg/dl
• CONTROL group:
– target 180 to 200 mg/dL.
• Stopped because of
significant reduction in
mortality 24
42%
reduced
Mortalit
y
25
IIT Reductions in Morbidity
46%
35%
41%
44%
35%
25%
Transfusions: 50% 26
Portland Diabetic Project
Furnary et al. 2004, Endocr Pract
• 17-year prospective, NON randomized 4864
patients with diabetes + open-heart surgery
• Increasing BS levels directly associated with
– death,
– deep sternal wound infections (DSWI),
– length of hospital stay (LOS), and
– hospital cost.
• Continuous INSULIN, target BS < 150 mg/dL for
3- post op days, reduced …
– death by 57%
– DSWI by 66%,
– (P<0.0001 for both)
27
Connecticut Study
Krinsley JS: Mayo Clin Proc, 2004
• 800 patients from a medical surgical ICU
• Target BS < 140 mg/dl
• Mortality decreased 29%
• LOS in ICU decreased 11%
• Renal insufficiency diminished by 75%
• Transfusions patients decreased by 19%
• No increase in nurse staffing
• No significant increase in hypoglycemia
occurred (0.35 vs. 0.34%).
28
Is it really true?
29
Pathophysiologic
Basis
30
Detrimental effects of
Hyperglycemia
• impairs immune function
– neutrophil function is reduced,
– complement binding is attenuated,
– monocyte phagocytic function is
disrupted PMN defect
• proinflammatory & prothrombotic
• cells membranes are altered
31
Pathophysiologic basis for benefits
Insulin ..
• regulates vasomotor function and
contractility of the myocardium
• stimulates nitric oxide production,
• improves endothelial function
• lowers cytokines
• improves protein balance and fat
metabolism
32
Infusing Lowering
Insulin BS
• complementary or synergistic
• overall improvements in immune,
hemodynamic, and metabolic functions
33
So What’s the catch?
How tight is too tight? 34
Hypoglycemia
35
Hypoglycemia
• Incidence
– Van den Berghe 0.05% vs 0.007%
– Krinsley: 0.35 vs. 0.34%
• Prevention
– abrupt interruption of Dextrose or continuous
feeds
– monitoring
• Treatment
• Risk-benefit ratio
36
Implementing (TGC)
37
TGC: Principles
• Insulin: Intravenous & continuous
• BS monitoring: hourly at least initially
• Essentially Nurse-led
• Adjustment protocol based not prn
• … and then, no two protocols are like
38
39
Complexity & variability of
Published Protocol
• Nine protocols reviewed
• From 27 to 800 patients.
• Target: 80-110 mg/dL, to 126-207 mg/dL
• Titration: based only on current BS level, OR
current & previous BS, insulin sensitivity and
concurrent nutrition.
• Insulin adjustments: Units or % of previous dose
• BS checks: hourly, but varied in subsequent
frequency
• Mean time to achieve target 2 to 15 hours.
• Hypoglycemia threshold: from 40 to 70 mg/dl
40
Insulin Protocols: Bottom line
41
Multitrauma Neuro ICU
ICU 12 beds 10 beds
PICU 10 SICU 19
beds
CT ICU 12
8 ICU’s beds
100 ICU beds!
Neurotrauma
ICU 12 beds
MICU 10 to
29 beds
CCU 15 beds
So what’s happening at UMMS? 42
UMMS: Tight Glycemic Control
• Multidisciplinary team
• UMMS protocol: couple of years
• Implementation attempted …….
• Let’s look at the protocol
43
UMMS Challenges
• Badia Faddoul, RN, Dept of
Clinical Effectiveness
44
What’s going on in the PICU?
• Before July 11, 2005 • After July 8, 2005
• NOTHING! • A LOT!
• Approached to
develop a computer
version
• July 8:
Multidisciplinary team
• July 9, 10: Movie
tickets
• July 11th prototype &
first patient
45
46
PICU: Glucose Optimizer pilot ..
• First patient experience
– Over 60 days,
– over 1500 Protocol manipulations
– More than 15 nurses
– Minimal orientation of first few nurses
– Cruise control
– Even travelling nurses, relatively new nurses
– Demo program
– In actual use
47
Anesthesia & TGC
Anestheisa
Implications 48
Intraoperative Glycemia
• Paucity of published studies
– Hyperinsulinemic clamp
• 2004, the American Association of Clinical
Endocrinologists: inpatient & peri-operative
guidelines, ASA input
• 110 mg/dl as the upper limit during the
perioperative period.
• American College of Endocrinology Position Statement on Inpatient
Diabetes and Metabolic Control. Endocrine Practice. 2004;
10(1):77-82.
49
Future
• Address hyperglycemia research on many
fronts
• National online survey
• Comparative study: Paper vs computerized
• Hospital wide implementation: Intranet
• Extremely rapid implementation cycle in
other hospitals, locally, nationally
50
Future directions
• Palm pilot based program
• Integrating program with Glucometer
• Web-based nursing in-service &
competancy
• Will intra-op TGC improve outcomes
• Randomized study in PICU
51
This ICU has not yet implemented tight glucose control!
Until then, please pardon the inconvenience of our 40%
increased Mortality Rate!
52
We have come a long way !
… Gluc.
Optimizer
2005
Best & Banting, 1921 Berghe 2001
53
• A spoonful of sugar
makes the ….
– mortality go up
– infections go up
– ICU stay go up
– transfusions go up
– polyneuropathy
– dialysis go up
– ventilators go up
– costs go up
– ……..
54
Some answers
•Hyperglycemia is v. common
•Hyperglycemia IS Bad
•Normoglycemia IS Good
•Tight Glycemic Control can
be achieved
•We will take the challenge of
implementation at UMMS
•Lot’s going on in the PICU
•Future is exciting
55
Thank you !
56
References
• Finney, SJ, et al. Glucose control & mortality in
critically ill patients. JAMA 290:15, 2003.
• McGowen, KC, et al. Stress induced hyperglycemia.
Critical Care Clinics 17:1, 2001.
• Montori, VM, et al. Hyperglycemia in acutely ill
patients. JAMA 288:17, 2002.
• Van den Berghe, G. Insulin therapy for the critically
ill patient. Clinical Cornerstone 5:2, 2003.
• Van den Berghe, G, et al. Outcome benefit of
intensive insulin therapy in the critically ill: Insulin
dose vs. glycemic control. Critical Care Medicine 31:2,
2003.
57
58
59
1921 to 2001
60
61
62
C254H377N65O76S6
63
• 3,500 diabetic patients, CABG,
– 57% decrease in mortality
– significant decrease in major infectious
complications
• Furnary AP et al. Continuous insulin infusion reduces mortality in
patients with diabetes undergoing coronary artery bypass grafting. J
Thorac Cardiovasc Surg. 2003
64
65
Perioperative outcomes in
cardiac surgery patients
• Intraoperative hyperglycemia is an
independent risk factor for complications,
including death, after cardiac surgery
• Gandhi et al, Mayo Clin Proc. 2005
66
Hyperglycemia in ICU
• Metabolic changes in response to stress
of illness
• insulin secretion
• stress hormones (cortisol,
catecholamines, GH, glucagon)
• cytokines (TNFα , IL-1)
• Results in gluconeogenesis,
glycogenolysis, lipolysis, proteolysis
67
Causes of…
INSULIN INSULIN
RESISTANCE DEFICIENCY
• Pressors • Advanced age
• Corticosteroids • Hypothermia
• Sepsis • Hypoxemia
• Uremia • DM
• Cirrhosis • Pancreatitis
• Obesity
• Bed rest
68
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