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

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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?

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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

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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)

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Is Hyperglycemia bad?

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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

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Let’s look at the evidence ..

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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

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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

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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.

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Hyperglycemia & Stroke Capes et al, Stroke 2001Kiers 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

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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

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Pregnancy & Hyperglycemia

• It is well-known that pregnancy complicated by uncontrolled diabetes results in poor fetal outcomes

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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

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Pediatric evidence …2 Hyperglycemia (>126 mg/dl)

Very Common:

86%

MORTALITYHigher peak &

longer duration of

Hyperglycemia in Non-survivors

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Pediatric evidence …35.7 times

more likely to DIE

for highest BS > 120 mg/dl in first

10 days

Hyperglycemia (>120 mg/dl)

Very Common:

75%

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Yes, Hyperglycemia =

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If HYPERGLYCEMIA is bad …

Is NORMOGLYCEMIA good?

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The Case for Normglycemia / Tight Glyemic control (TGC)

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1921–Face of Insulin

Millions of diabetic lives saved ..

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Face of Insulin: today

? Millions of Non-diabetic lives too ?

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DIGAMI trialDiabetes 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%)

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2001

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• 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

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42% reduced Mortalit

y

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IIT Reductions in Morbidity

41%

46%

44%

25%

35%

35%

Transfusions: 50%

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Portland Diabetic ProjectFurnary 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)

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Connecticut StudyKrinsley 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%).

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Is it really true?

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Pathophysiologic Basis

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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

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Pathophysiologic basis for benefitsInsulin ..

• regulates vasomotor function and contractility of the myocardium

• stimulates nitric oxide production,

• improves endothelial function

• lowers cytokines

• improves protein balance and fat metabolism

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• complementary or synergistic

• overall improvements in immune, hemodynamic, and metabolic functions

InfusingInsulin

Lowering BS

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So What’s the catch?

How tight is too tight?

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Hypoglycemia

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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

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Implementing (TGC)

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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

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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

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Insulin Protocols: Bottom line

42So what’s happening at UMMS?

SICU 19 beds

Neuro ICU 10 beds

CT ICU 12 beds

Multitrauma ICU 12 beds

Neurotrauma ICU 12 beds

MICU 10 to 29 beds

CCU 15 beds

PICU 10

8 ICU’s

100 ICU beds!

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UMMS: Tight Glycemic Control

• Multidisciplinary team

• UMMS protocol: couple of years

• Implementation attempted …….

• Let’s look at the protocol

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UMMS Challenges

• Badia Faddoul, RN, Dept of Clinical Effectiveness

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What’s going on in the PICU?

• Before July 11, 2005• NOTHING!

• After July 8, 2005• A LOT!• Approached to

develop a computer version

• July 8: Multidisciplinary team

• July 9, 10: Movie tickets

• July 11th prototype & first patient

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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

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Anesthesia & TGC

Anestheisa Implications

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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.

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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

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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

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This ICU has not yet implemented tight glucose control!

Until then, please pardon the inconvenience of our 40% increased Mortality Rate!

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We have come a long way !

Best & Banting, 1921

… Gluc. Optimizer

2005

Berghe 2001

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• 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– ……..

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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

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Thank you !

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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.

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1921 to 2001

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C254H377N65O76S6

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• 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

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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

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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

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Causes of…

INSULINRESISTANCE• Pressors• Corticosteroids• Sepsis• Uremia• Cirrhosis• Obesity• Bed rest

INSULINDEFICIENCY• Advanced age• Hypothermia• Hypoxemia• DM• Pancreatitis