Anesthesia and the HepatoBiliary System

1. Anesthesia and the HepatoBiliary System

2. Objectives • Hepatic Physiology • Mechanisms of Hepatocellular Injury • Acute Parenchymal Liver Disease • Assessment of Liver Function • Preoperative Considerations • Intraoperative Considerations

3. Objectives • Chronic Parenchymal Liver Disease • Preoperative Considerations • Intraoperative Considerations • Postoperative Liver Dysfunction • Anesthetic Considerations

4. Hepatic Physiology • Liver Blood Flow • 25% of Cardiac output • Hepatic artery ~25% of blood flow • Portal vein ~ 75% of blood flow • Hepatic Veins empty into the inferior vena cava

5. Splanchnic Circulation Fig 17.1

6. Hepatic Microcirculation • Portal Axis consists of a terminal portal venule, a hepatic arteriole and a bile ductule • Liver Acinusfunctional microvascular unit • Zone 1- rich in Oxygen, mitochondria • Oxidative metabolism, synthesis of glycogen • Zone 2- transition • Zone 3- lowest in Oxygen, anaerobic metabolism, Cytochrome P-450 • Biotransformation of drugs, chemicals, and toxins • Most sensitive to damage due to ischemia, hypoxia, congestion

7. Microvascular Structure Fig 17.3

8. Regulation of Liver Blood Flow • Intrinsic Regulation • Autoregulation • Metabolic control • Hepatic Arterial Buffer Response • Decreases in portal blood flow causes increased hepatic arterial blood flow • Extrinsic Regulation • Neural Control • Hormones • Effects of Anesthesia

9. Regulation of Liver Blood Flow • Individual anesthetics • Isoflurane and Sevoflurane preserve Hepatic blood flow • Upper Abdominal Surgery • Hepatic blood flow reduced by 60 % • Regional Subarachnoid Block of T4 • Reduces 20% of Hepatic blood flow

10. Functions of the Liver - I • Metabolic • Protein: Albumin major protein, Coagulation factors except Factor VIII • Carbohydrates: Glucose homeostasis via gluconeogenesis and glycogenolysis • Lipids: Degraded to Acetylcoenzyme, a key molecule in synthesis of ATP, Cholesterol and Phospholipids

11. Functions of the Liver-II • Bilirubin conjugation and secretion • Bile formation • Hematologic function • Hematopoiesis 9th to 24th week gestation • Clears Fibrin Degradation Products and Lactate • Important in shock and massive blood loss and transfusion

12. Functions of the Liver-III • Humoral function • Insulin degraded 50% in the first pass • T4 to T3 conversion • Aldosterone, estrogen, androgen, ADH all are inactivated by the liver • Liver disease thus, results in endocrine abnormalities • Immunologic function • Kupffer cells phagocytose antigens

13. Functions of the Liver-IV • Drug Biotransformation • Make drugs more polar for efficient elimination • Phase I Reaction • Cytochrome P450 system • Oxidation/reduction • Mixed –Function Oxidases • Phase II Reaction • Conjugation most commonly catalyzed by UDP-glucuronyl transferase

14. Factors Affecting Hepatic Drug Metabolism • Drugs with high extraction ratio are affected more by changes in HBF • Propranolol, Lidocaine, Meperedine • Poorly extracted drugs are more sensitive to intrinsic ability of the liver to eliminate a drug • Diazepam, Phenytoin, Coumadin • Anesthesia • Ketamine induces its own metabolism, therefore rapid tolerance can occur

15. Evaluation of Liver Function • Laboratory Tests: • ALT, AST, Alkaline phosphatase with 5’-nucleotidase • Serum Albumin, Gamma-globulin • PT (best estimate of hepatic function) • Antinuclear Antibody • Chronic Active Hepatitis 75% • Antimitochondrial antibody • Primary biliary cirrhosis 100% • Radiologic Techniques • Cholangiography, Radionuclide and Ultra sound

16. Acute Viral Hepatitis • Postpone elective surgery • High mortality and morbidity • Acute encephalopathy, avoid premed sedatives • Frequent blood glucose monitoring for hypoglycemia • Correction of Coagulopathy with Vit K, FFP and platelet transfusion

17. Algorithm for Abnormal Transaminase levels fig 54-1A

18. Algorithm for Abnormal Transaminase levels fig 54-1B

19. Algorithm for Abnormal Transaminase levels fig 54-1C

20. Chronic Liver Diseaseor Cirrhosis PreOp considerations • Portal hypertension may lead to GI hemorrhage • Rx Fluid resuscitation • Must be done carefully to avoid rebleeding of varices • Vasopressin and Octreotide constrict splanchnic arteriolar bed

21. Chronic Liver Disease PreOp • Ascites is due to portal hypertension and sodium retention that occurs with cirrhosis • Rx with Sodium and water restriction and diuretics • Diuretics • Cause hyponatremia and hyperkalemia • Check and correct electrolytes

22. Chronic Liver Disease /PreOp • Paracentesis of Ascites • Not exceed 1 Liter/day for a daily weight loss of 0.5 to 1.0 kg • 1 liter of ascites fluid contains 10 grams of Albumin • Each liter of ascites removed must be replaced by 50 ml of 25% Albumin

23. Chronic Liver Disease /PreOp • Hepatorenal syndrome can be precipitated • By aggressive paracentesis, potent diuretics like Zaroxolyn • Avoid aminoglycosides (contraindicated), NSAIDS, renal contrast, volume depletion • Hepatic Encephalopathy • Dysarthria, flapping tremor, hyperreflexia • Avoid long acting benzodiazepines, high dose opiates and diuretics

24. Chronic Liver Disease /PreOp • Child-Turcotte-Pugh Classification • Lab and clinical criteria to predict operative survival in patients with Cirrhosis • Class C, Surgical risk of Mortality rate 50% • Serum bilirubin > 3 mg/dl • Albumin < 3 g/dl • PT > 6 sec of control • Ascites uncontrolled, encephalopathy advanced, nutrition poor

25. Chronic Liver Disease /IntraOp • Optimum drugs or techniques are unknown • Avoid or reduce dose of drugs excreted via the liver such as Lidocaine, Meperidine, Morphine • Succinylcholine acceptable, effects are not prolonged significantly • NDMB may have prolonged duration of action • Atracurium may be better as it is eliminated by Hoffman elimination • Vecuronium < 0.6 mg/kg, Atracurium < 0.15 mg/kg • Avoid Pancuronium

26. Chronic Liver Disease/IntraOp • Most IV induction agents are metabolized by the liver but recovery depends on redistribution. Safe to use Propofol, Thiopental • For Inhalational agents, Isoflurane and Sevoflurane are better than Halothane as Hepatic Blood Flow is decreased to a lesser degree • Fentanyl and Sufentanil single dose bolus does not change elimination half life • Remifentanil is a safer choice as it is degraded by tissue and RBC Esterases

27. Chronic Liver Disease/IntraOp • Laparotomy with Abdominal Paracentesis of Ascites • Maintain Intravascular volume, • Rx with Albumin • Patients with GI hemorrhage • Receiving blood products may have decreased clearance of Citrate which can lead to hypocalcemia • Bleeding diathesis • Rx with FFP or Prothrombin complex to correct PT within 3 secs of normal • Transfuse if platelets < 100,000/uL, Rx with DDAVP

28. PostOp Complications • Reversible minor changes are common • PostOp Jaundice may be due to hemolysis of transfused blood • Shock Liver syndrome can occur if prolonged hypotension persisted • Marked by severe hepato-cellular necrosis • SerumTransaminases levels increased > 10 fold • Bleeding, Sepsis, Renal failure

29. Summary-I • Liver functions include • Protein synthesis • Drugs, fat and hormone metabolism • Immunologic function • Bilirubin formation and excretion • Glucose homeostasis

30. Summary-II • For Acute Hepatitis • Postpone all elective procedures as the mortality rate is very high • For unexpected high Transaminase levels • Repeat LFTs, if stable or decreasing may proceed with surgery • Otherwise GI consult should be obtained

31. Summary-III • In Chronic Liver disease pre-op issues include • GI hemorrhage • Ascites, electrolyte imbalances • Hypoglycemia, • Coagulopathy and bleeding disorder

32. Summary-IV • In Chronic liver disease intra-operatively • Avoid or reduce drugs that are eliminated by liver • IV inductions agents are considered safe • Inhalational agents • Use Isoflurane, avoid Halothane • Avoid Sevoflurane if risk of Hepato-Renal Syndrome • Muscle Relaxants all are acceptable • Vecuronium and Rocuronium have increased duration of action

33. Summary-V • In Chronic liver disease intra-operatively • Opioids can be used • Maintain Intravascular volume • Consider replacing 50 mL of 25% Albumin for each liter of ascites fluid removed • Blood products can cause hypocalcemia and Calcium need to be replaced

34. Summary-VI • Post-Op Liver dysfunctions • Reversible minor changes are common • Post op Jaundice may be due to hemolysis, but other causes should be sought • Shock Liver syndrome presented by hepatocellular necrosis can occur due to prolonged hypotension

35. References • Anesthesia, Fifth Edition/ Ronald D. Miller, Hepatic Physiology, Chapter 17 & Anesthesia and the Hepatobiliary System, Chapter 54. • Anesthesia and Co-Existing Disease, Fourth Edition/ Robert K Stoelting, Stephen F. Dierdorf, Diseases of the Liver and Biliary Tract, Chapter 18. • Clinical Anesthesia, Fourth Edition/ Paul G. Barash, et.al., Anesthesia and the Liver, Chapter 39