Anesthesia and the HepatoBiliary

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

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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 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

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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 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
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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

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