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Glucose Control In Cardiac Surgery. Mike Poullis. Overview. Glucose basics Basic science Clinical diabetes Glucose control and cardiac surgery trial GIK GIK in cardiology patients GIK in surgical patients. Glucose metabolism . Glucose. Rest of body. Muscle. Liver. Insulin.
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Glucose Control In Cardiac Surgery Mike Poullis
Overview • Glucose basics • Basic science • Clinical diabetes • Glucose control and cardiac surgery trial • GIK • GIK in cardiology patients • GIK in surgical patients
Glucose metabolism Glucose Rest of body Muscle Liver Insulin
Hormonal Control • Insulin Liver and muscle • Glucagon 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
Metabolism • Glycolysis • TCA • Lactate • Cori cycle • Fat • Ketone production • Anion Gap • Heart metabolism • Terms • Glycolysis • Glycogenolysis • Glycogenesis • Gluconeogenesis
Glycolysis TCA
Lactic acid Glucose No oxygen Lactic acid Pyruvate 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
Fat Trigylceride Glycerol and 3 Fa’s Fatty acid FA FA Glycerol FA FA n
Lack insulin causes increased lipolysis. Peripheral tissues can’t cope. FFA are metabolised in liver to ketones
Acidosis - Ketones & Lactic Acid Cardiac Surgery Patients Ketones 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 • 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 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.
Our PROTOCOL • 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 non-alcoholic 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 • Irrespective of LIMA / RIMA / BIMA / Diathermy / Wax • Glucose control • Neutrophils • Blood supply • Microvascular • Macrovascular • Obese • Fracture Healing • 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 • EX Exogenous insulin or drugs • P Pituitary • L Liver • A Adrenal / autoantibodies • I Insulinoma • N 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