Glucose Control In Cardiac Surgery

1. Glucose Control In Cardiac Surgery Mike Poullis

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

3. Glucose metabolism Glucose Rest of body Muscle Liver Insulin

4. Hormonal Control • Insulin Liver and muscle • Glucagon Liver • Somatostatin • Site of action • Muscle and liver blood flow

5. Glucose metabolism • Glucose uptake depends on • Serum glucose • Blood flow • Insulin availability • Glucose doesn’t always cause acidosis • Diabetic hyperosmolar coma

6. Energy use in the body Glucose Pyruvate TCA cycle Oxygen ATP Energy

7. Basic science

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

9. Carbohydrate metabolism

10. Glycolysis TCA

11. Lactate

12. Lactic acid Glucose No oxygen Lactic acid Pyruvate TCA cycle Oxygen ATP Energy

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

14. Pyruvate

15. Lactate metabolism and Cori cycle

16. Gluconeogenesis

17. Glucose

18. Fat Trigylceride Glycerol and 3 Fa’s Fatty acid FA FA Glycerol FA FA n

19. Fat metabolism glucose and lactate regulate

20. Ketone productionStarvationandInsulin lack

21. Lack insulin causes increased lipolysis. Peripheral tissues can’t cope. FFA are metabolised in liver to ketones

22. Acidosis - Ketones & Lactic Acid Cardiac Surgery Patients Ketones Lactic Acid

23. Anion gap • What you can’t measure • (Na+ + K +) - (Cl - + HCO3 -) • Causes “KUSMAL” • Ketones • Uraemia • Salicylates • Methyl alcohol • Acid poisoning • Lactate

24. 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

25. 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

26. Normal & Abnormal Glucose Levels • Random • Fasting • Glucose tolerance test • Whole blood or plasma • Normal, impaired, Impaired fasting glycaemia, diabetic

27. 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

28. 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

29. Types of diabetes • Diet • Type I Insulin dependent • Type II Insulin resistance • MODY

30. Types of Oral Medication • Biguanide • Metformin • Sulphonyureas • Chlorpropamide, glibenclamide, gliclazide, tolbutamide • Glucosidases inhibitor • Acarbose • Thiazolidinedione • Troglitazone • Can mix with insulin • Beta blockers in diabetes

31. 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

32. 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

33. 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.

34. 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

35. ? 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

36. Phase Locked Loop • Sports car vs Morris minor @ 30 mph analogy

37. 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

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

39. Infection in Diabetes • Neutrophils • Blood supply • Microvascular • Macrovascular • No pain

40. 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

41. Dangers High and Low BM Acutely • High glucose damages already damaged brain • If low brain only organ irreversibly damaged

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

43. High BM on Bypass / ITU • Diabetic • Impaired • Poor perfusion • Large insulin boluses due to perfusion problem • No evidence insulin lack or resistance post op

44. 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

45. JTCVS trial • Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. • JTCVS. 2003;125(5):1007-21

46. 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

49. 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

50. 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