Beyond Pre-Anaesthetic Testing

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

17. Interpretation of Biochemical results

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

19. Hypoalbuminaemia • SignificanceAnaesthesiaWound healingeffusion formation • CausesIncreased lossReduced productionEffusion 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 infectionsFIV, FIP, Felv • B-cell derived neoplasiaLymphoma, myeloma, (plasmacytoma) • Non indigenous infectionsLeishmania, 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 dogEpistaxis 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 dogEpistaxis 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 agentsProduction of coagulation proteins

28. Diagnostic evaluation of liver disease Is liver disease present? • Hepatocellular damageALT • CholestasisALP

29. Hepatocyte Enzyme Distribution

30. Hepatic Lobule Anatomy

31. Cholestatic Enzyme Markers

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

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

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 criteriaHistory, 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

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, CatEHBDO 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 byRate of NH4 formation (protein breakdown)Rate of hepatic conversion to ureaRate 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 causeshypovolaemia, shock, reduced cardiac output, hypoadrenocorticism • Renal causescongenital, inflammatory, toxic, renal ischaemia, neoplasia • Post renal causesurinary 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. Increasingly common with age Need not be associated with leuconuria Leucocyte dipstick gives false positive Urinary Tract Infection In Cats

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