Download Glucose control in cardiac surgery

Glucose Control In Cardiac
Surgery
Mike Poullis
Overview
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Glucose basics
Basic science
Clinical diabetes
Glucose control and cardiac surgery trial
GIK
GIK in cardiology patients
GIK in surgical patients
Glucose metabolism
Glucose
Liver
Muscle
Insulin
Rest of body
Hormonal Control
• Insulin
• Glucagon
Liver and muscle
Liver
– Somatostatin
• Site of action
• Muscle and liver blood flow
Glucose metabolism
• Glucose uptake depends on
– Serum glucose
– Blood flow
– Insulin availability
• Glucose doesn’t always cause acidosis
– Diabetic hyperosmolar coma
Energy use in the body
Glucose
Pyruvate
TCA cycle
Oxygen
ATP
Energy
Basic science
Metabolism
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Glycolysis
TCA
Lactate
Cori cycle
Fat
Ketone production
Anion Gap
Heart metabolism
• Terms
– Glycolysis
– Glycogenolysis
– Glycogenesis
– Gluconeogenesis
Carbohydrate metabolism
Glycolysis
TCA
Lactate
Lactic acid
Glucose
No oxygen
Pyruvate
Lactic acid
TCA cycle
Oxygen
ATP
Energy
Lactic acidosis
• Increased production
– Tissue Hypoxia
– Circulatory shock
• Decreased utilisation
– Liver failure
– Circulatory shock
• Acidosis dangerous, Lactate harmless
• BE as surrogate marker
Pyruvate
Lactate metabolism and Cori cycle
Gluconeogenesis
Glucose
Fat
Trigylceride
Glycerol and 3 Fa’s
FA
FA
Glycerol
FA
Fatty acid
FA
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Fat metabolism glucose and lactate regulate
Ketone production
Starvation
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Insulin lack
Lack insulin causes increased lipolysis.
Peripheral tissues can’t cope.
FFA are metabolised in liver to ketones
Acidosis - Ketones & Lactic Acid
Ketones
Cardiac
Surgery
Patients
Lactic Acid
Anion gap
• What you can’t measure
• (Na+ + K +) - (Cl - + HCO3 -)
• Causes “KUSMAL”
– Ketones
– Uraemia
– Salicylates
– Methyl alcohol
– Acid poisoning
– Lactate
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
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
Normal & Abnormal Glucose Levels
• Random
• Fasting
• Glucose tolerance test
• Whole blood or plasma
• Normal, impaired, Impaired fasting glycaemia,
diabetic
• Diabetic
– Fasting plasma > 7.8 mmol/L
– GTT > 11.1 mmol/L @ 2 hours
• Impaired
– Fasting plasma 5.5 to 7.8 mmol/L
– GTT 7.8 to 11.1 mmol/L @ 2 hours
• Impaired fasting glycaemia
– Fasting 6.1 to 6.9 mmol/L
– GTT <7.8 mmol/L @ 2 hours
• Normal
– Random 3 to 5.5 mmol/L
– Fasting <5.5 mmol/L
– GTT < 7.8 mmol/L @2 hours
Glucose Tolerance Test
• Full
• Mini
• Full
– Fast for 12 hours water allowed
– 75g Glucose (Lucozade)
– Glucose @ 2 hours and fasting
• Mini
– ? can of lucozade and BM @ 30 minutes
• Only TWO indications
– Fasting BM > 6.1
– Or fasting BM < 6.1 but diabetic symptoms
Types of diabetes
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Diet
Type I Insulin dependent
Type II Insulin resistance
MODY
Types of Oral Medication
• Biguanide
– Metformin
• Sulphonyureas
– Chlorpropamide, glibenclamide, gliclazide, tolbutamide
• Glucosidases inhibitor
– Acarbose
• Thiazolidinedione
– Troglitazone
• Can mix with insulin
• Beta blockers in diabetes
• 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
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
Alberti regime
• The substitute for intermittent subcutaneous injections is a singlebag 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 steadystate 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.
Our PROTOCOL
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10 % Dextrose @ 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
? Problems with our protocol
• 10 % Dextrose @ 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
Phase Locked Loop
Sports car vs Morris minor @ 30 mph analogy
Fluids in Diabetes
• If BM >10 0.9 % NaCl, then change to Dextrose NaCl
• Hartmanns in Off pump non diabetics ? Physio replacement
• Fatty liver disease, non-alcoholic steatohepatitis, and nonalcoholic fatty liver disease (FLD, NASH and NAFLD)
– Liver impairment
– retain sodium 2nd hyperaldosteronism
– ? lactate metabolism important
Monitoring Diabetics
• Clinical eg feet, BP, fundoscopy, urine
• BM
• U and Es, 24 Hr urine protein
• HbA1c
– Fructosamine
Infection in Diabetes
• Neutrophils
• Blood supply
– Microvascular
– Macrovascular
• No pain
Healing in Diabetic Sternums
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Irrespective of LIMA / RIMA / BIMA / Diathermy / Wax
Glucose control
Neutrophils
Blood supply
– Microvascular
– Macrovascular
• Obese
• Fracture Healing
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Renal failure
Cardiac output
Liver disease
Nutrition
Dangers High and Low BM Acutely
• High glucose damages already damaged
brain
• If low brain only organ irreversibly damaged
EXPLAIN Hypoglycaemia
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Exogenous insulin or drugs
Pituitary
Liver
Adrenal / autoantibodies
Insulinoma
Neoplasia
High BM on Bypass / ITU
• Diabetic
• Impaired
• Poor perfusion
• Large insulin boluses due to perfusion problem
• No evidence insulin lack or resistance post op
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
JTCVS trial
• Continuous insulin infusion reduces mortality
in patients with diabetes undergoing coronary
artery bypass grafting.
• JTCVS. 2003;125(5):1007-21
Study
• 15 year period
• Diabetic patients
• N=3554 CABG
• Cross clamp fibrillation (ischaemic model)
• 1987-1997 sc insulin, 1992-2001 civ insulin
• Sliding scale
• BM target 100 to 150 mg/dL
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
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 @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
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
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 < 1/3
IIB - crackles > 1/3
Killip Class III
- symptoms on minimal activity or rest / pulmonary oedema
Killip Class IV
- cardiogenic shock
GIK
• Glucose-insulin-potassium infusion
inpatients treated with primary angioplasty
for acute myocardial infarction: the glucoseinsulin-potassium study: a randomized trial.
• J Am Coll Cardiol. 2003 Sep 3;42(5):784-91
Study
• 1998 to 2001
• N=940 acute MI eligible for acute PTCA
• Randomised to either GIK infusion over 8 to
12 hours or nothing
• 30 day mortality
All Patients in GIK trial
Killip class I patients
Breakdown by Risk Factor
Results
• Overall no difference
• Killip class I 1.2 %(GIK) vs 4.2 %(control)
• Killip class >2 36 %(GIK) vs 26.5 %(control)
• Killip I are the survivors anyway !
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 %
Thank you