Tight Glycemic Control Implementation, the key to success by txi18521

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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
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1921   to   2001




                   60
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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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