Anesthesia and the HepatoBiliary System

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Objectives

• Hepatic Physiology– Mechanisms of Hepatocellular Injury

• Acute Parenchymal Liver Disease– Assessment of Liver Function– Preoperative Considerations– Intraoperative Considerations

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Objectives

• Chronic Parenchymal Liver Disease– Preoperative Considerations– Intraoperative Considerations

• Postoperative Liver Dysfunction– Anesthetic Considerations

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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

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Splanchnic Circulation Fig 17.1

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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

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Microvascular Structure Fig 17.3

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Algorithm for Abnormal Transaminase levels fig 54-1A

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Algorithm for Abnormal Transaminase levels fig 54-1B

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Algorithm for Abnormal Transaminase levels fig 54-1C

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Summary-I

• Liver functions include– Protein synthesis– Drugs, fat and hormone metabolism– Immunologic function– Bilirubin formation and excretion– Glucose homeostasis

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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

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Summary-III

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

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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

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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

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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

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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