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Anesthesia and the HepatoBiliary System 1 Objectives • Hepatic Physiology – Mechanisms of Hepatocellular Injury • Acute Parenchymal Liver Disease – Assessment of Liver Function – Preoperative Considerations – Intraoperative Considerations 2 Objectives • Chronic Parenchymal Liver Disease – Preoperative Considerations – Intraoperative Considerations • Postoperative Liver Dysfunction – Anesthetic Considerations 3 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 4 Splanchnic Circulation Fig 17.1 5 Hepatic Microcirculation • Portal Axis consists of a terminal portal venule, a hepatic arteriole and a bile ductule • Liver Acinus functional 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 6 Microvascular Structure Fig 17.3 7 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 8 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 9 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 10 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 11 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 12 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 13 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 14 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 15 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 16 Algorithm for Abnormal Transaminase levels fig 54-1A 17 Algorithm for Abnormal Transaminase levels fig 54-1B 18 Algorithm for Abnormal Transaminase levels fig 54-1C 19 Chronic Liver Disease or 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 20 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 21 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 22 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 23 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 24 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 25 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 26 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 DDAVP27 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 28 Summary-I • Liver functions include – – – – – Protein synthesis Drugs, fat and hormone metabolism Immunologic function Bilirubin formation and excretion Glucose homeostasis 29 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 30 Summary-III • In Chronic Liver disease pre-op issues include – – – – GI hemorrhage Ascites, electrolyte imbalances Hypoglycemia, Coagulopathy and bleeding disorder 31 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 32 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 33 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 34 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 35