Glucose Control In Cardiac Surgery

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Glucose Control In Cardiac Surgery

• Mike Poullis

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Overview

• Glucose basics
• Basic science
• Clinical diabetes
• Glucose control and cardiac surgery trial
• GIK
• GIK in cardiology patients
• GIK in surgical patients

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Glucose metabolism
Glucose
Rest of body
Muscle
Liver
Insulin
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Hormonal Control

• Insulin Liver and muscle
• Glucagon Liver
• Somatostatin
• Site of action
• Muscle and liver blood flow

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Glucose metabolism

• Glucose uptake depends on
• Serum glucose
• Blood flow
• Insulin availability
• Glucose doesnt always cause acidosis
• Diabetic hyperosmolar coma

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Energy use in the body
Glucose
Pyruvate
TCA cycle
Oxygen
ATP
Energy
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Basic science
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Metabolism

• Glycolysis
• TCA
• Lactate
• Cori cycle
• Fat
• Ketone production
• Anion Gap
• Heart metabolism
• Terms
• Glycolysis
• Glycogenolysis
• Glycogenesis
• Gluconeogenesis

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Carbohydrate metabolism
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Glycolysis
TCA
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Lactate
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Lactic acid
Glucose
No oxygen
Lactic acid
Pyruvate
TCA cycle
Oxygen
ATP
Energy
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Lactic acidosis

• Increased production
• Tissue Hypoxia
• Circulatory shock
• Decreased utilisation
• Liver failure
• Circulatory shock
• Acidosis dangerous, Lactate harmless
• BE as surrogate marker

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Pyruvate
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Lactate metabolism and Cori cycle
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Gluconeogenesis
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Glucose
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Fat
Trigylceride Glycerol and 3 Fas Fatty
acid
FA
FA
Glycerol
FA
FA
n
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Fat metabolism glucose and lactate regulate
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Ketone productionStarvation andInsulin lack
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Lack insulin causes increased lipolysis.
Peripheral tissues cant cope. FFA are
metabolised in liver to ketones
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Acidosis - Ketones Lactic Acid
Cardiac Surgery Patients
Ketones
Lactic Acid
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Anion gap

• What you cant measure
• (Na K ) - (Cl - HCO3 -)
• Causes KUSMAL
• Ketones
• Uraemia
• Salicylates
• Methyl alcohol
• Acid poisoning
• Lactate

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Heart Metabolism Omnivore

• Fatty acids provide 60 to 100 energy
• Lactate
• Carbohydrate fuels have better response to
  ischaemic events
• Free Fatty acids thought to be bad
• Toxic
• Membrane damage
• Arrhythmias
• Metabolic inefficiency
• Decreased cardiac function

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Clinical Diabetes

• Normal Abnormal Glucose Levels
• Glucose Tolerance Test
• Types of diabetes
• Types of Oral Medication
• Insulin Regimes
• Alberti regime
• Our PROTOCOL
• ? Problems with our protocol
• Fluids in Diabetes
• Monitoring Diabetics
• Infection in Diabetes
• Healing in Diabetic Sternums
• Dangers High and Low BM Acutely
• EXPLAIN Hypoglycaemia
• High BM on Bypass / ITU
• Inotropes and BMs

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Normal Abnormal Glucose Levels

• Random
• Fasting
• Glucose tolerance test
• Whole blood or plasma
• Normal, impaired, Impaired fasting glycaemia,
  diabetic

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• Diabetic
• Fasting plasma gt 7.8 mmol/L
• GTT gt 11.1 mmol/L _at_ 2 hours
• Impaired
• Fasting plasma 5.5 to 7.8 mmol/L
• GTT 7.8 to 11.1 mmol/L _at_ 2 hours
• Impaired fasting glycaemia
• Fasting 6.1 to 6.9 mmol/L
• GTT lt7.8 mmol/L _at_ 2 hours
• Normal
• Random 3 to 5.5 mmol/L
• Fasting lt5.5 mmol/L
• GTT lt 7.8 mmol/L _at_2 hours

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Glucose Tolerance Test

• Full
• Mini
• Full
• Fast for 12 hours water allowed
• 75g Glucose (Lucozade)
• Glucose _at_ 2 hours and fasting
• Mini
• ? can of lucozade and BM _at_ 30 minutes
• Only TWO indications
• Fasting BM gt 6.1
• Or fasting BM lt 6.1 but diabetic symptoms

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Types of diabetes

• Diet
• Type I Insulin dependent
• Type II Insulin resistance
• MODY

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Types of Oral Medication

• Biguanide
• Metformin
• Sulphonyureas
• Chlorpropamide, glibenclamide, gliclazide,
  tolbutamide
• Glucosidases inhibitor
• Acarbose
• Thiazolidinedione
• Troglitazone
• Can mix with insulin
• Beta blockers in diabetes

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• Sulphonyureas
• Increase beta cell sensitivity to insulin
• Can cause hypoglycaemia
• Glibenclamide blocks myocardial k channels
• Biguanide
• reduce hepatic glucose production
• lactic acidosis
• do not cause hypoglycaemia
• Glucosidases inhibitor
• Brush border of the small intestine
• Inhibits glucose absorption
• Thiazolidinedione
• increases the sensitivity of peripheral tissues
  to insulin

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Insulin Regimes

• SC
• IV
• Insulin regimes
• Sliding scale
• Alberti regime
• SSSI
• Converting to sc regimes
• Must be eating and drinking normally
• Add up previous 24 Hr total units
• od, bd, tds
• 2/3 given am 1/3 given pm
• 2/3 intermediate acting 1/3 quick acting

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Alberti regime

• The substitute for intermittent subcutaneous
  injections is a single-bag intravenous solution
• 10 aqueous dextrose solution, regular insulin,
  and potassium (ie, glucose-insulin-potassium
  GIK solution)
• The scientific rationale for this is an attempt
  to closely mimic steady-state physiology
• 5-10 g of dextrose, 1-2 U of insulin, and 100-125
  mL of fluid per hour to matches glucose
  production, insulin secretion, and replacement of
  insensitive fluid losses.
• Safety feature inadvertent over infusion or
  under infusion delivers equal proportions of
  dextrose and insulin.

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Our PROTOCOL

• 10 Dextrose _at_ 60 ml/hr
• Insulin 50U/50mL
• K APP
• Inotrope solution adjusted to take account of
  calories in dextrose
• No Hartmanns (lactate) as can cause lactic
  acidosis
• BM aim for 5 to 12 mmol/L

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? Problems with our protocol

• 10 Dextrose _at_ 60 ml/hr (1400ml)
• More accurate control and prevent hypos
• Insulin 50U/50mL
• K APP
• Inotrope solution adjusted to take account of
  calories in dextrose
• 140 350g/24 Hr but 1.4L 10 Dextrose 140g
• Ignores the rest energy requirement fat / protein
• Why use TPN ?
• No Hartmanns (lactate) as can cause lactic
  acidosis
• BM aim for 5 to 12 mmol/L

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Phase Locked Loop

• Sports car vs Morris minor _at_ 30 mph analogy

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Fluids in Diabetes

• If BM gt10 0.9 NaCl, then change to Dextrose
  NaCl
• Hartmanns in Off pump non diabetics ? Physio
  replacement
• Fatty liver disease, non-alcoholic
  steatohepatitis, and non-alcoholic fatty liver
  disease (FLD, NASH and NAFLD)
• Liver impairment
• retain sodium 2nd hyperaldosteronism
• ? lactate metabolism important

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Monitoring Diabetics

• Clinical eg feet, BP, fundoscopy, urine
• BM
• U and Es, 24 Hr urine protein
• HbA1c
• Fructosamine

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Infection in Diabetes

• Neutrophils
• Blood supply
• Microvascular
• Macrovascular
• No pain

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Healing in Diabetic Sternums

• Irrespective of LIMA / RIMA / BIMA / Diathermy /
  Wax
• Glucose control
• Neutrophils
• Blood supply
• Microvascular
• Macrovascular
• Obese
• Fracture Healing
• Renal failure
• Cardiac output
• Liver disease
• Nutrition

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Dangers High and Low BM Acutely

• High glucose damages already damaged brain
• If low brain only organ irreversibly damaged

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EXPLAIN Hypoglycaemia

• EX Exogenous insulin or drugs
• P Pituitary
• L Liver
• A Adrenal / autoantibodies
• I Insulinoma
• N Neoplasia

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High BM on Bypass / ITU

• Diabetic
• Impaired
• Poor perfusion
• Large insulin boluses due to perfusion problem
• No evidence insulin lack or resistance post op

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Inotropes and BMs

• Liver flow
• Beta2
• neuroglycopenic response
• Beta blockers
• Alpha (inhibit insulin release)
• neuroglycopenic response
• Peripheral perfusion (muscle)
• Fluid they are made up in

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JTCVS trial

• Continuous insulin infusion reduces mortality in
  patients with diabetes undergoing coronary artery
  bypass grafting.
• JTCVS. 2003125(5)1007-21

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Study

• 15 year period
• Diabetic patients
• N3554 CABG
• Cross clamp fibrillation (ischaemic model)
• 1987-1997 sc insulin, 1992-2001 civ insulin
• Sliding scale
• BM target 100 to 150 mg/dL

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Results

• Mortality 2.5 (CIV) vs 5.3 (SC)
• Glucose control 177 vs 213
• Multivariate analysis CIV protective effect
  against death
• ? Any one stupid enough today to rely on SC
  insulin on a cardiac surgery patient ITU ???
• BM target 100 to 150 mg/dL is only 5.5 to 8.3
  mmol/L

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GIK (Glucose-insulin-potassium)

• 40 year old concept initially based on ecg
  changes
• Reduction infarct size and increased survival
• Different GIK regimes (delay in administration,
  amount and duration)
• 30 glucose, 50 U insulin, 80 mmol KCL _at_1.5
  ml/(kg.h)
• Volume infusion important in heart failure
• Most studies not in diabetics
• Unstable angina, MI, post MI, angioplasty,
  surgery
• A number of negative studies

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Mechanism of GIK

• Debated
• Energy substrate for mechanically overloaded
  heart
• Decreases FFA concentration
• Increases glycolytic ATP production
• Reduction reperfusion apoptosis
• May act via up regulating GLUT-1 receptor

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KILLIP Classification

• Killip Class I
• - no symptoms with normal activities, clear lungs
• Killip Class II
• - normal activities initiate symptoms, but
  subside with rest
• IIA - crackles lt 1/3
• IIB - crackles gt 1/3
• Killip Class III
• - symptoms on minimal activity or rest /
  pulmonary oedema
• Killip Class IV
• - cardiogenic shock

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GIK

• Glucose-insulin-potassium infusion inpatients
  treated with primary angioplasty for acute
  myocardial infarction the glucose-insulin-potassi
  um study a randomized trial.
• J Am Coll Cardiol. 2003 Sep 342(5)784-91

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Study

• 1998 to 2001
• N940 acute MI eligible for acute PTCA
• Randomised to either GIK infusion over 8 to 12
  hours or nothing
• 30 day mortality

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All Patients in GIK trial
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Killip class I patients
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Breakdown by Risk Factor
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Results

• Overall no difference
• Killip class I 1.2 (GIK) vs 4.2 (control)
• Killip class gt2 36 (GIK) vs 26.5 (control)
• Killip I are the survivors anyway !

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GIK and Cardiac Surgery

• Texas Heart Institute
• 322 consecutive patients
• Refractory heart failure post cardiac surgery
• Standard care vs standard care GIK
• Standard care Inotropes and IABP
• Mortality reduced from 26.6 to 17.6

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Thank you