ANAESTHETIC IMPLICATIONS IN ACUTE PARENCHYMAL LIVER DISEASE

1. ANAESTHETIC IMPLICATIONS IN ACUTE PARENCHYMAL LIVER DISEASE Dr. MansiArora University College of Medical Science & GTB Hospital, Delhi

2. Modified Child-Pugh Score

3. CHILD SCORE AND SURGERY • Child A - safely undergo elective surgery. • Child B - may undergo elective surgery after optimisation with caution. accepted criterion for listing to OLT. • Child C - contraindication for elective surgery.

4. MELD SCORE • Objective score ( no interindividual variation in contrast to child –pugh score that has 2 subjective component). • Designed to predict survival after TIPS 2 control bleeding varices but now used for prioritizing patients for OLT. MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL)] + 6.43 (x 0 for alcoholics/cholestasis) (x 1 for remainder)

5. MELD SCORE AND SURGERY • Meld < 10 - safely undergo elective surgery. • Meld10 -15 - may undergo elective surgery after optimisation with caution. accepted criterion for listing to OLT • Meld > 15 - contraindication for elective surgery

6. ANAESTHETIC IMPLICATIONSIN ACUTE PARENCHYMALLIVER DISEASE By-Mansi Arora Moderator-Dr. Sharmila Ahuja

7. SPECIAL CONCERNS • Advanced liver disease may impair the elimination, prolong the half life & potentiate the effects of several drugs. • So drugs with their adjusted dosages should be used cautiously • Data suggests that patient with acute hepatitis are at increased risk for hepatic failure and death after elective surgery. • Post op. jaundice may occur as a result of intraop. Hepatobilliary injury, anaesthetic induced hepatotoxicity, severe hepatic hypoperfusion and medications (Miller’s,7ed)

8. ANAESTHETIC GOALS • In a patient with acute parenchymal liver disease - main objective is to Minimize physiological insult to liver and kidney. Achieved by- • Maintain HBF • Maintain O2 supply-demand relationship in liver. Adequate pulmonary ventilation and CVS function

9. ANAESTHETIC GOALS(cont…) • Maintain renal perfusion Avoid- • Hypotension (adequate fluid balance) • Hypoxia • Hypocarbia/Hypercarbia • Hypothermia/Hyperthermia • Hypoglycaemia/ Hyperglycaemia .

10. Various anaesthetic drugs & techniques affect the hepatic function by alteration in HBF(mainly) or directly causing hepatocellular injury. AND • Hepatic dysfunction also alters the pharmacokinetic -s of the drug. So altering their dosages , clearance and metabolism.

11. EFFECT OF VARIOUS ANAESTHETIC DRUGS ON LIVER

12. VolatileAnaesthetics • All volatile anaesthetics decrease total hepatic blood flow. • THBF= PBF + HABF • Techniques of measuring PBF/HABF :- • Plasma clearance of Indocynine green dye • TEE • Doppler • Most profound decrease in hepatic blood flow :-Halothane

13. Volatile Anaesthetics(cont.) • Mechanism of decrease in THBF - • Decrease in MAP. • Decrease in CO • HALOTHANE - more effect on HABF : Hepatic artery vasoconstriction. • Disrupt compensatory mech.- Hepatic arterial buffer response. • Also decreases hepatic O2 delivery & hepatic venous O2 saturation.

14. Volatile Anaesthetics(cont…) • ISOFLURANE - Increase flow velocity in hepatic sinusoids Preserve microvascular blood flow • DESFLURANE, SEVOFLURANE Preserve total hepatic blood flow

16. EFFECT OF VOLATILE AGENTS ON HBF

17. INTRAVENOUS AGENTS • THIOPENTONE – capacity limited drug. Dose has to be reduced for induction because of decreased protein binding & reduction in enzyme activity. • Thiopentone- Higher dose is needed in alcoholic with compensated liver disease because of CYP-450 enzyme induction by alcohol. • Duration of action of single dose will not be prolonged as the major determinant of a single dose is redistribution

18. INTRAVENOUS AGENTS(cont..) KETAMINE-Flow limited drug having high extraction ratio & high hepatic clearance. • Maintains the CO by sympathomimetic action. • So maintains the HBF ETOMIDATE-Highly protein bound drug with high vd & clearance. • Maintains the CO & MAP-so minimal effect on HBF. • Metabolism by-hepatic microsomal enzymes and esterases-so dosages should be decreased in hepatic dysfunction.

19. INTRAVENOUS AGENTS(cont..) • Metabolism of PROPOFOL is dependent on Hepatic blood flow as it is primarily metabolized in liver . • Propofol cause the maximum decrease in HBF among the induction agents. Thus resulting in prolongation of action even after single dose. • Propofol in contrast to other iv induction agents has extrahepatic metabolism. • Slow titrated dose of induction agents with smooth intubation will have little impact on the HBF.

20. Effect of Hepatic Dysfunction on the Drug Pharmacokinetics

21. MUSCLE RELAXANTS • Succinylcholine– Duration of action rarely gets prolonged despite reduced pseudocholinesterase level. • Duration of action of Pancuronium and Rocuronium gets prolonged because of increased Vd and impaired hepatic metabolism (altered pharmacokinetics). • Duration of action of Vecuronium (<0.15mg/kg) may be slightly prolonged or unaffected as it is excreted in bile (30%). • Duration of action of Mivacurium gets prolonged because of the reduced plasma cholinesterase level.

22. MUSCLE RELAXANTS(cont..) • Atracurium and cis-atracurium – Duration of action not affected as both the drugs undergo organ independent elimination – Ester hydrolysis and Hoffmans degradation. • Duration of action of above drugs are infact reduced because of increased Vd & increased binding to globulins.

23. To prevent residual muscle weakness in the post op. period because of altered pharmacokinetics, careful monitoring of the neuromuscular function is needed.

24. OPIOIDS • Morphine- Hepatic metabolism Extrahepatic metabolism • Decreased plasma protein binding- increased bioavailability. • Interval of dosages-should be increased to 1.5-2 fold. • Spasm of sphincter of Oddi. • Should be used cautiously in pts. with liver disease.

25. OPIOIDS • Fentanyl and Sufentanil- Duration of action of single dose is not altered in compensated liver disease. • Alfentanil- Duration of action is prolonged because of the increased free fraction of the drug. • Remifentanil- Duration of action is unaffected as it is metabolised by nonspecific esterase. • Meperidine- 50% decrease in clearance leading to doubling of half life.

26. NITROUS OXIDE • Nitrous Oxide containing anaesthetics does not cause liver injury in the absence of impaired hepatic oxygenation. • Nitrous Oxide may exacerbate hepatic damage in the presence of impaired hepatic oxygenation through sympathetic stimulant action and methionine synthase inhibition.

27. Drugs in Liver Dysfunction

28. Drugs in Liver Dysfunction

29. ANAESTHESIA-RELATED FACTORS • ARTIFICIAL VENTILATION- • Decreases hepatic blood flow • Significant decrease with addition of PEEP. • HYPOXIA- • Arteriolar constriction & decrease in flow. • HYPOCAPNIA & HYPERCAPNIA- • Both causes decrease in HBF.

30. Factors Affecting HBF • Supine posture Postprandial state • Acidosis Acute hepatitis • Beta agonist Phenobarbitone • Glucagon Dopamine Wylie and churchill-Davidson

31. Factors Affecting HBF Upright posture Hypocarbia Hypoxia IPPV/PEEP Sepsis Haemorrhage Mesentric traction Alpha agonist Beta blockers Volatile anaesthetics I/V induction agents Regional anaesthesia

32. SURGERY RELATED FACTORS • Nature and extent of surgery - Most important determinant of hepatic blood flow & postop. Hepatic dysfunction. • Risk greatest with- • Abdominal surgery • Billiary surgery • Cardiac surgery • Increased risk of morbidity & mortality of any type of surgery in presence of acute parenchymal liver disease.

33. SURGERY RELATED FACTORS • In case of acute parenchymal liver disease-postpone elective surgery until liver dysfunction is investigated & managed. • In emergency cases- optimize the patient in whatever time available before surgery.

34. AIMS OF INTRAOP. MANAGEMENT • Avoid & minimize physiological insults to the liver. • Avoid renal insults. • Preserve cardiac output with fluid loading. • Maintain- Normovolemia Normocapnia (PaCO2 around 40mmHg) • Monitor acid base disturbances & electrolyte abnormalities. • Preservation of urine output@1-2ml/kg/hr Fluids Mannitol Dopamine

35. AIMS OF INTRAOP. MANAGEMENT(cont..) • Accurate replacement of blood loss - crystalloids/ colloids/packed cells • Maintain normoglycemia- (prone to hypoglycemia). • Maintain normothermia (hypothermia worsens coagulopathy) - warm fluids, humidification, space blankets etc. • Avoid nephrotoxic antibiotics & NSAIDS. • Invasive monitoring may be considered.

36. INTRAOPERATIVE MONITORING • ECG (H.R.), B.P, SpO2 • ETCO2 • CVP • Urine Output • Core body temperature • NM monitoring • ABG with S.E. • Blood Sugar • Blood Loss • If needed- Hb, PT, PTTK

37. INDUCTION OF ANAESTHESIA • Preoxygenation • 3-5 min. with 100% O2 • Choice of Agents • Induction Agents • Thiopentone • Etomidate • Propofol • Muscle Relaxants • Atracurium • Vecuronium • Succinylcholine • Volatile Anaesthetics • Isoflurane • Sevoflurane • Desflurane

38. MAITENANCE OF ANAESTHESIA • O2 + N2O + Inhalational agent + Muscle relaxant. • Controlled ventilation:- • Avoid large tidal volumes. • Resp. rate of 10-12 breaths/min. • Add PEEP if necessary. • Avoid high airway pressure.

39. EMERGENCE FROM ANAESTHESIA • Reversal of NM blockade should be guided by NM monitoring. • Done only when patient completely out of muscle relaxants effects. • Extubate the trachea when patient completely awake. • Reverse with Neostigmine(0.03-0.05mg/kg)and Atropine(0.01mg/kg)

40. POSTOPERATIVE MANAGEMENT • Achieve cardiovascular stability- fluids, dopamine.. • Maintain oxygenation • Supplement O2 up to 12-16 hrs post op. • Continue Mannitol if used intraop. (till 36 hrs postoperatively) • Maintain Urine Output(0.5 ml/kg/hr) • Replace urine losses • Avoid Dyselectrolytemia

41. POSTOPERATIVE MANAGEMENT(cont..) • Adequate analgesia :- • Intravenous agents ( tailored doses) • Regional anaesthesia (if coagulation profile is normal) • Epidural • Intercostal nerve block • Avoid Hypothermia / Hyperthermia • Replace blood/ blood products. • Proper antibiotics in post op. period

42. POSTOPERATIVE COMPLICATIONS • Impaired Consciousness - over sedation. • Impaired Respiration - opioid overdose. • Inadequate reversal. • Chest infection. • Oliguria & renal failure. • Deterioration of hepatic function/ postop. Jaundice.

43. REGIONAL ANAESTHESIA • Coagulation profile should be within normal limits. • If there is marked hypotension (>20% baseline)- • Decreased HBF • Increased chances of renal failure • Dosages of Lignocaine & Bupivacaine should be reduced upto 50%. • Epidural anaesthesia has an added advantage of CVS stability.

44. REGIONAL ANAESTHESIA(cont…) Key Points- • Avoid hypotension. • Maintain adequate fluid balance. • Maintain urine output ≥ 1ml/kg. • Avoid vasopressors (If Warranted Dopamine may be used.)

45. SUMMARY • Patients with acute parenchymal liver injury have increased morbidity & mortality after elective surgery. • Choice of anaesthetic agents & techniques should aim at minimizing physiological insult to liver and kidney. • Dosages of drugs should be altered in accordance with degree of hepatic dysfunction present. • Meticulous post.op monitoring is required with maintenance of oxygenation &circulation.

46. REFERENCES • Miller RD. Miller’s Anaesthesia.7th ed. Anaesthesia and the hepatobiliary system;66. • Wylie and Churchill-Davidson’s-A Practice of Anaesthesia; 7thed.The physiology of liver;17:297-307. • Roberts-Prys. International Practice of anaesthesia. Volume1;70-73. • Friedman LS, Maddrey WC: Surgery in the patient with liver disease. Med Clin North Am 1987 May; 71(3): 453-76. • MorganGE. Clinical Anaesthesiology.4 ed.Hepatic physiology& Anaesthesia;34:773-801

47. THANK YOU

48. ANAESTHETIC GOALS(cont..) Choose an appropriate anaesthetic agent- • Effect on HBF • Metabolism

49. Modified Child-Pugh Score

50. CHILD SCORE AND SURGERY • Child A - safely undergo elective surgery. • Child B - may undergo elective surgery after optimisation with caution. accepted criterion for listing to OLT. • Child C - contraindication for elective surgery.