1. Beyond Pre-Anaesthetic Testing Nick Carmichael BVM&S, BSc VetSci(Hons), Diploma VCS(Syd), Diploma RCPath, Diplomate ECVCP, MRCVS

2. Aims of pre-anaesthetic testing Screen for the presence of intercurrent disease Allow adjustments in anaesthetics/ drugs used to be made Provide baseline data if problem develops later

3. Benefits of pre-anaesthetic testing Safer anaesthesia Appropriate perioperative management Early identification of clinically silent problems

4. Drawbacks of pre-anaesthetic testing Cost benefit analysis “False positive” screening test results Inappropriate labelling of cases “False negative” screening test results Decision time pressure

5. Cost Benefit Analysis Detection rate of abnormalities ~ 1-11% veterinary Detection rate of abnormalities~ 2% man Evidence of reduced anaesthetic morbidity and mortality~ ??

6. What are the major anaesthetic risks? Excessive anaesthetic administered Hypotension Cardiac rhythm abnormalities/ arrest Ventilation/perfusion imbalances Would pre- anaesthetic bloods predict / ameliorate these?

7. Pre-anaesthetic testing requirements Sensitive Specific Relate to organ function Low cost

8. Diagnostic Profiles Contains grouped tests related to organ function Tests provide complimentary information Tests included relate to a presenting sign Assists in localisation/ narrowing of the DDx Screens Contains a single test per organ Single most sensitive test included Test array is fixed Provides yes/no information regarding normality SCREENS VS PROFILES

9. Pre-anaesthetic screen components FBC Total protein Urea ALT ALP Glucose (Electrolytes)

10. Full Blood Count abnormalities in Pre-anaesthetic screens

11. Tiny, boxer male 3yr Total protein 68 g/L (54.0 -77.0 ) Urea 3.3 mmol/L (2.0 -9.0 ) Creatinine 91 umol/L (40.0 -106.0) Alk Phos * 707 U/L High (0.0 -150.0 ) ALT * 233 U/L High (0.0 -25.0 ) Total bilirubin 6 umol/L (0.0 -20.0 ) Glucose 5.3 mmol/L (3.5-6.5)

12. Tiny, boxer male 3yr RBC * 2.83 x10^12/L Low (5.0 -8.5 ) Hb * 6.9 g/dl Low (12.0 -18.0 ) HCT *21.9 % Low (37.0 -55.0 ) MCV 77.0 fl (60.0 -80.0 ) MCH 24.3 pg (19.0 -26.0 ) MCHC 31.5 g/dl (31.5 -37.0 ) Platelets * 66 x10^9/L Low (160 -500 ) WBC * 1.89 x10^9/L Low (6.0 -15.0 ) Neutrophils * 39% 0.74 x10^9/L Low (3.0 -11.5 ) Lymphocytes 57% 1.08 x10^9/L (1.0 -4.8 ) Monocytes 3% 0.06 x10^9/L (0.0 -1.3 ) Eosinophils 1% 0.02 x10^9/L (0.0 -1.25 )

13. FBC abnormalities White Cells : Atypical Lymphocytes

14. FBC abnormalities Red Cells: Schistocytes

15. FBC abnormalities Platelets: Thrombocytopenia & Platelet Clumps

16. Daisy, CKCS FN 2yrs Total protein ↑86 68g/L Albumin 32 32 g/L Globulin ↑54 36g/L Total calcium 2.86 2.70 mmol/L Phosphate ↑3.51 2.10 mmol/L Urea ↑14.9 ↑13.3mmol/L Creatinine 101 ↑152umol/L Alk Phos ↑578 ↑455U/L GLDH ↑87 12 U/L Gamma GT 25 25 U/L Total bilirubin ↑30 6umol/L Bile acids ↑26.7 9.7umol/L Glucose 6.4 5.6mmol/L

17. Interpretation of Biochemical results

18. Total Protein Normal TP 50:50 alb:globNormal TP, 10:90 AG

19. Hypoalbuminaemia Significance Anaesthesia Wound healing effusion formation Causes Increased loss Reduced production Effusion formation

20. Hypoalbuminaemia Investigation Evidence of effusion /exudation Evidence of increased renal/ GI loss? Evidence of inflammation? Evidence of impaired hepatic function?

21. Hyperglobulinaemia Associated with Inflammation Viral infection Neoplasia

22. Severe Hyperglobulinaemia Effects Impaired primary haemostasis Blood hyperviscosity Differentials Feline viral infections FIV, FIP, Felv B-cell derived neoplasia Lymphoma, myeloma, (plasmacytoma) Non indigenous infections Leishmania, Ehrlichia, Borrelia

23. Hyperglobulinaemia Diagnostic evaluation Clinical examination FBC – smear evaluation Viral screening Serum protein electrophoresis Non indigenous infection serology/ PCR testing

24. Tess 11y, FN Cross breed dog Epistaxis for 1 year, NAD on skull Xray RBC ↓ 3.67 x10^12/L 5 - 8.5 Hb ↓ 9.0 g/dl 12 - 18 HCT ↓ 27.8 % 37 - 55 MCV 76.0 fl 60 - 80 MCH 24.5 pg 19 - 26 MCHC 32.4 g/dl 31.5 - 37 Platelets 357 x10^9/L 160 - 500 WBC 8.46 x10^9/L 6 - 15 Neutrophils 77% 6.5x10^9/L 3 - 11.5 Lymphocytes 20% 1.6x10^9/L 1 - 4.8 Monocytes 0.% 0.0x10^9/L 0 - 1.3 Eosinophils 3% 0.2x10^9/L 0 - 1.25

25. Rouleaux

26. Tess 11y, FN Cross breed dog Epistaxis for 1 year, NAD on skull Xray Total protein ↑ 138 g/L 54.0 - 77.0 Albumin ↓ 22 g/L 25.0 - 37.0 Globulin ↑ 116 g/L 25.0 - 52.0 A:G ratio ↓ 0.2 0.6 - 1.5 Total calcium 2.60 mmol/L 2.0 - 3.0 Corrected Calcium 2.96 mmol/l 2.0 - 3.0 Urea ↑ 9.4 mmol/L 2.0 - 9 Creatinine 97 umol/L 40 - 106 Alk Phos 4 U/L 0 - 150 ALT ↑ 45 U/L 0 - 25 Total bilirubin 7 umol/L 0 - 20 Glucose 5.7 mmol/L 3.5 - 6.5

27. Diagnostic evaluation of liver disease Useful information Is there liver disease present likely to be exacerbated by anaesthetic agents? Is liver function significantly impaired? Metabolising/clearing anaesthetic agents Production of coagulation proteins

28. Diagnostic evaluation of liver disease Is liver disease present? Hepatocellular damage ALT Cholestasis ALP

29. Hepatocyte Enzyme Distribution

30. Hepatic Lobule Anatomy

31. Cholestatic Enzyme Markers

32. Hepatocellular ALT:High Low ALP 1/2 life:66 hours 6 hours Steroid induced ALP:Yes No Bilirubinuria:Normal Abnormal Cholangiohepatitis:Rare Common Liver Enzymes in Dogs and Cats

33. Transaminases & Dehydrogenases ALT AST GLDH Measure integrity of cell membranes Degree of increase correlates with number of hepatocytes involved AST increases correlate with more severe hepatocelullar injury Measure integrity of cell membranes Degree of increase correlates with number of hepatocytes involved AST increases correlate with more severe hepatocelullar injury

35. Interpreting liver Enzymes Increased ALT Primary hepatic disease? Reactive hepatopathy? Induced change? Derived from muscle?

36. Interpreting liver Enzymes Increased ALP Primary cholestatic problem? Reactive hepatopathy? Induced change? Hepatic lipidosis? Canine benign hepatic nodular hyperplasia? Physiological increase?

37. Interpreting liver Enzymes Differentiating primary and secondary hepatopathies Clinical criteria History, physical exam Presence of hyperbilirubinaemia Extent of increase in ALT Changes in endogenous liver function indicators  OFTEN FURTHER TESTING WILL BE REQUIRED

38. Liver Function Tests Endogenous Albumin, urea, Glucose, Cholesterol, Coagulation Factors, NH3 Endogenous Albumin, urea, Glucose, Cholesterol, Coagulation Factors, NH3

39. “Alarm” blood screen abnormalities in liver disease Marked increases in ALT Increased bilirubin Reductions in urea, albumin, A:G ratio, cholesterol Microcytosis +/- anaemia

40. Further investigation of liver abnormalities Review history and physical findings Run a liver profile with FBC Include post prandial bile acids Consider abdominal imaging

41. Liver Function Tests

42. Darby Pandy Total protein 67 64 g/L Albumin 33 33 g/L Globulin 34 31 g/L AG ratio 1.0 1.1 Urea 2.5 4.3 mmol/L Creatinine 76 87 umol/L Alk Phos ↑ 302 865 U/L ALT ↑ 81 46 U/L AST 27 26 U/L GLDH ↑ 12 7 U/L Gamma GT 1 11 U/L Total bilirubin 9 5 umol/L Glucose 5.6 5.8 mmol/L Cholesterol 6.5 5.7 mmol/L Bile acids ↑ 162.2 0.9 umol/L Post bile acids ↑ 270.8 20.8 umol/L

43. Tinker, 11y, DSH, Cat EHBDO Oct June Total protein 55 67 g/L Albumin ↓20 - g/L Globulin 35 - g/L AG ratio 0.6 - Sodium 157 154 mmol/L Potassium ↓3.5 4.3 mmol/L Na:K ratio ↑ 45 36 Urea 4.7 11.1 mmol/L Creatinine 114 138 umol/L Alk Phos ↑ 324 89 U/L ALT ↑ 1798 64 U/L Total bilirubin ↑ 78 -umol/L Bile acids ↑ 388.0 -umol/L

44. Evaluating renal function Urea used as a sentinel molecule for nitrogenous waste in blood Urea concentration is affected by Rate of NH4 formation (protein breakdown) Rate of hepatic conversion to urea Rate of renal clearance Rate of intestinal excretion Serum urea represents a composite of these factors

45. Evaluating renal function Urea is more sensitive but less specific for renal function than creatinine Hypovolaemia allows increased renal reabsorption of urea Protein load from GI tract is variable GI bleeding may result in dogs in urea increase unrelated to GFR

46. Causes of azotaemia Prerenal causes hypovolaemia, shock, reduced cardiac output, hypoadrenocorticism Renal causes congenital, inflammatory, toxic, renal ischaemia, neoplasia Post renal causes urinary tract obstruction or leakage

47. Investigation of renal disease Document persistence of the azotaemia Urinalysis SG, dipstick, sediment (culture) Complete the profile

48. Urine Refactometer

49. Urinary Tract Infection In Cats Increasingly common with age Need not be associated with leuconuria Leucocyte dipstick gives false positive

50. Reduced serum urea Reduced protein intake Reduced protein absorbtion Reduced hepatic synthesis of urea Increased renal clearance of urea

51. Serum Electrolytes Sodium Potassium Chloride

52. Hypokalaemia Predominantly K+ is intracellular Serum K+ is insensitive for depletion of total body potassium Most common in polyuric cats associated with increased GFR Muscle weakness, anorexia, vomiting, cardiac arrythmias

53. Tabatha, 16y, DSH,FN Weight loss, needs dental preOp check Total protein 66 g/L 54.0 - 80.0 Albumin 26 g/L 21 - 39 Globulin 40 g/L 15 - 57 Sodium 147 mmol/L 125 - 160 Potassium 3.3 mmol/L 3.6 - 6.0 Na:K ratio 45 32 - 41 Total calcium 2.28 mmol/L 2.0 - 3.0 Urea 8.7 mmol/L 4.0 - 12.0 Creatinine 111 umol/L 80 - 180 Alk Phos ↑ 291 U/L 0 - 50 ALT ↑ 136 U/L 0 - 40 Total bilirubin 5 umol/L 0 - 10 Glucose 15.5 mmol/L 3.5 - 6.6 Total T4 ↑ 167.0 nmol/L 5.0 - 50.0

54. Hyperkalaemia May accompany hypoaldosteronism in Addison’s disease Affected by blood pH Increased in renal insufficiency and urinary obstruction Occasionally seen with severe muscle damage Cardiac conduction disturbances, depression, weakness

55. Investigation of Electrolyte Abnormalities Exclude artefacts preanalytical, analytical Check for underlying disease Correct pre-operatively

56. Hypercalcaemia  Closely controlled element involved in neuromuscular transmission  Minor deviations may be significant  Present as free, protein bound and chelated forms in blood  Malignant neoplasia, parathyroid neoplasia, Addisons, CRF

57. Preanaesthetic blood testing

58. Elective blood Testing Sampling at consultation or vaccination Removes time pressure for medical decision making Allows further testing if required ahead of anaesthesia Increases flexibility of test procedures Improves client communication and understanding

59. Elective blood Testing Aims Screen for clinically occult disease where early intervention is beneficial Provides baseline data Retained for future use To guide additional testing Facilitate improved perioperative management

60. Elective blood testing Test selection is based on History, signalment, physical findings Screen or profile may be appropriate incorporate appropriate additional tests Ensure pre-analytical & analytical error is minimised Retain and compare data for an individual over time