Anesthesia and the HepatoBiliary System

1. Anesthesia and the HepatoBiliary System Gurdip Bhatia, MD Charles E. Smith, MD MetroHealth Medical Center Case Western Reserve University Cleveland, Ohio March 30, 2004

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