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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 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 • • • • • • • • 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 n Fat metabolism glucose and lactate regulate Ketone production Starvation and 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 • • • • 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 • • • • 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 • • • • 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 P L A I N 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