ANESTHESIA FOR

PATIENTS WITH LIVER

DISEASE
PRESENTER : DR RIZWAN ANSARI (AP)
FCPS
BILAWAL MEDICAL COLLEGE LUMHS
INTRODUCTION
• The liver is a large, complex organ with a multitude of different functions.

• Patients with liver failure present a significant challenge to the anaesthetist.

• A good understanding of normal liver physiology, causes of liver dysfunction

and its multi-system impact on patient function is very important in
managing these patients.
FUNCTIONS OF LIVER
• Amino acid synthesis, gluconeogenesis, glycogenolysis, glycogenesis

• Protein metabolism, lipid metabolism, lipogenesis and lipoprotein synthesis

• Coagulation factor production (fibrinogen, prothrombin, V, VII, IX, X and XI,

protein C and protein S)

• Bile production and excretion, IGF-1 and thrombopoietin production.

• Albumin production, hormone synthesis

FUNCTIONS OF LIVER
• Storage of glycogen, vitamin A, D, B12, iron and copper.

• Drug and toxin metabolism:

• PHASE I: oxidation/reduction/hydrolysis, alteration of intrinsic

molecular structure, P450 based drug detoxification

• PHASE II : conjugation with second substance to increase polarity,

gluconeogensis, betaoxidation of fatty acids and cholesterol synthesis
TESTS OF LIVER FUNCTION
• LFTs measure the concentrations of various proteins and enzymes in
the blood that are either produced by liver cells or released when
liver cells are damaged.

• They can be divided into

1. Tests of liver function
2. Tests of cell injury
3. Tests of biliary obstruction
Tests of liver function
Prothrombin time (PT)

• Is a measure of the extrinsic pathway of coagulation, it measures

factors I, II, V, VII and X.

• Prolongation can reflect deficiencies of vitamin K relating to impaired

absorption from poor quality bile production or abnormalities in
factor VII synthesis, both relating to liver dysfunction.
Tests of liver function
Albumin

• Albumin is synthesized in the liver; low serum albumin may reflect

liver dysfunction.

• Hypo-albuminaemia also occurs in malnutrition, nephrotic syndrome,

malabsorptive states and late pregnancy.
Tests of cell injury
Alanine Amino Transferase (ALT) and Aspartate Amino Transferase
(AST)

• These tests are used to detect liver cell damage, however there is no
correlation between levels and degree of damage.

• Elevated ALT and AST out of proportion with the enzymes indicative
of biliary obstruction, suggests an intra-hepatic problem.
Tests of biliary obstruction
• Bilirubin
• Bilirubin is elevated by any of the following: haemolysis, biliary
stricture, hepatitis, cirrhosis, drugs (eg
• antipsychotics and sulphonamides) and Gilberts syndrome. Jaundice
of the sclera becomes noticeable
• when serum levels 2-3 mg/dl, jaundice of the skin indicates even
higher levels.
Tests of biliary obstruction
• Alkaline Phosphatase (ALP)

• ALP is present in all tissues throughout the body. ALP is elevated in

biliary obstruction, pregnancy and as a by-product of osteoblast
activity eg Paget’s disease.
Tests of biliary obstruction
• Gamma Glutamyl Transpeptidase (GGT)
• GGT is present in the cell membrane of many tissues. Elevation is seen in liver,
biliary system and pancreatic disease.

• Isolated elevation may also suggest significant alcohol ingestion.

• GGT is elevated by several drugs including barbiturates, phenytoin, St John’s

Wort and non-steroidal anti-inflammatorydrugs (NSAIDs).

• Elevation is also seen in congestive cardiac failure (CCF).

LIVER FAILURE
• Liver disease has a spectrum of severity from subclinical disease to
end-stage liver disease

• The range of symptoms a patient has depends on whether the disease

presentation is acute or chronic.

• Worldwide the major cause of liver disease is viral infection and

paracetamol overdose
ACUTE LIVER FAILURE
• Acute liver failure ranges from non-specific nausea and abdominal
discomfort to confusion, agitation and coma.

• Diagnosis is confirmed by abnormalities of liver function tests and

coagulation, in conjunction with features of encephalopathy.

• Hepatic encephalopathy is due to the accumulation of toxic products

of protein breakdown and gut bacterial metabolism. When the liver is
unable to clear these substances it can result in elevated ammonia.
GRADES OF ENCEPHALOPATHY
Encephalopathy severity is graded 1 – 4:
• Grade 1 – slow mental function
• Grade 2 – inappropriate behaviour
• Grade 3 – permanent somnolence
• Grade 4 – coma
CHRONIC LIVER DISEASE
• Chronic liver disease involves a disease process of progressive destruction
and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.

• The range of symptoms shown by patients with chronic liver disease is

often superimposed on a background of chronic ill health and poor
nutrition.

• The common complications of chronic liver disease such as ascites, hyper-

splensism and a collateral venous circulation producing lower
oesophageal and gastric varices, all result from portal hypertension.
 CLASSIFICATION OF LIVER DISEASE
• The Childs Pugh system
• This classification can indicate severity of disease and prognosis.
 Child-Pugh A – score <6
 Child-Pugh B – score 7-9
 Child-Pugh C – score >10

Points Class One-year survival Two-year survival

5–6 A 100% 85%
7–9 B 80% 60%
10–15 C 45% 35%
CHILDS PUGH SYSTEM
PERI OPERATIVE ANESTHESIA
MANAGEMENT
• PRE OPERATIVE ASSESSMENT

• INTRA OPERATIVE MANAGEMENT

• POST OPERATIVE CONCERNS

PRE OPERATIVE ASSESSMENT AND
OPTIMIZATION
• Prediction of surgical risk is based on the degree of liver dysfunction,
type of surgery and the preclinical status of the patient.

• The Childs Pugh score can be used to estimate risk of peri-operative

mortality.

• Recent figures suggest patients with Childs A have 5-10% peri-operative

mortality after abdominal surgery, compared to Childs B where it rises
to 25-30% and Childs C where peri-operative mortality is >50% in all
types of abdominal surgery.
PRE OPERATIVE ASSESSMENT AND
OPTIMIZATION
• Patients undergoing emergency surgery are at an even greater risk.

• The lack of opportunity to correct reversible factors such as

electrolyte imbalance, coagulopathy and the clinical manifestations of
portal hypertension such as ascites and encephalopathy all have an
impact.

• The presence of malnutrition, sepsis and significant blood loss

increase risks further still.
PRE OPERATIVE ASSESSMENT AND
OPTIMIZATION
• Full blood count
• Pro-thrombin
• Baseline renal
• Identification and correction of electrolyte disturbances.
• ECG and echocardiography
• Exercise ECG or stress
• CXR or ultrasound imaging of chest
• Pulmonary function tests
PRE OPERATIVE ASSESSMENT AND
OPTIMIZATION
• Optimization of electrolytes, intravascular volume status, coagulation and
infection status may be best achieved by admission to a critical care bed, and
this should be considered on a case by case basis.

• Preoperative vit K and FFP administration to correct the coagulation defect,

and cryoprecipitate may also be required if the PT remains prolonged.

• Bleeding time reduction should be guided by levels, and may need

prophylactic desmopressin (DDAVP) administration, platelet transfusion,
thromboelastogram use and expert haematological advice. Tranexamic acid
may also be helpful.
PRE OPERATIVE ASSESSMENT AND
OPTIMIZATION
• Ascites present at the time of surgery can lead to wound dehiscence,
abdominal wall herniation and respiratory compromise secondary to
diaphragmatic splinting.

• Pre-operative diuresis or aggressive paracentesis may be required.

• Nutritional health should be addressed preoperatively wherever

possible.
PRE OPERATIVE ASSESSMENT AND
OPTIMIZATION
• Dietetic input and vitamin supplementation should occur as early as
possible in the pre-operative process.

• Gastric emptying is often delayed in this population and as such

aspiration is a greater risk, pre-medication with H2 antagonists may
be advisable.

• Sedative premedication should be avoided as it may precipitate

encephalopathy
PRE OPERATIVE ASSESSMENT AND
OPTIMIZATION
• It should be remembered that encephalopathy in the postoperative
period of non-hepatic surgery is associated with greatly elevated
postoperative mortality.
INTRA OPERATIVE MANAGEMENT
Monitoring
• Routine monitoring should be established pre-induction.

• Monitoring of neuromuscular blockade, urine output, lactate, glucose, electrolytes

and temperature, with active warming devices available, should all occur throughout
the intra-operative period

• The potential for significant blood loss means large bore IV access is ideal.

• Invasive monitoring by means of arterial line and CVP can be very helpful and is used
almost universally when dealing with Childs B and C patients.
INTRA OPERATIVE MANAGEMENT
• Oesophageal doppler and trans-esophageal echo (TEE) can be useful,
but the presence of varices may preclude the use of these modalities.

• Use of a PA catheter, or arterial waveform analysis techniques such as

LiDCO is alternatives for cardiac output monitoring.

• All will provide information to aid the maintenance of intravascular

volume and the need for vasopressors to maintain adequate
perfusion pressures.
INTRA OPERATIVE MANAGEMENT
• The increased risk of infection in this group means strict aseptic
technique and antibiotic prophylaxis needs to be carefully considered.

• Depletion of glycogen stores may result in perioperative hypoglycaemia

and a background infusion of dextrose may be required.

• N-acetylcysteine infusion in patients with fulminant hepatic failure may

improve oxygen delivery and consumption and reduce basedeficit.
INTRA OPERATIVE MANAGEMENT
• Anaesthetic choice

• Propofol is probably the most commonly used induction agent in this group as it
undergoes considerable extra-hepatic metabolism.

• If thiopentone is to be used, a reduced dose is again needed, as reduction in plasma

proteins causes an increased unbound fraction of the drug.

• Chronic alcohol use may increase IV anaesthetic requirements however all agents
should beused with care.
INTRA OPERATIVE MANAGEMENT
• In terms of muscle relaxant choice, suxamethonium may have a
prolonged duration of action due to reduced pseudocholinesterase
concentrations slowing its metabolism, although in practise this is
unlikely to be clinically significant.

• Vecuronium and rocuronium have a prolonged elimination phase in

severe disease.

• Atracurium and cisatarcurium are better options as they are not reliant
on hepatic excretion.
INTRA OPERATIVE MANAGEMENT
• Monitoring of neuromuscular blockade is advised whatever the choice of agent.

• Choice of opioids can be difficult.

• The elimination of morphine is delayed in cirrhotic patients due to reduced

hepatic blood flow and extraction ratio.

• In patients with associated renal failure, accumulation of the active metabolite

morphine-6-glucuronide will occur. Morphine may therefore precipitate
encephalopathy and is possibly best avoided in severe liver dysfunction.
INTRA OPERATIVE MANAGEMENT
• Fentanyl in low doses may be a better option as it is renally excreted,
however it will accumulate in larger doses.

• The elimination of alfentanil is reduced whilst its volume of

distribution is increased.

• A deficiency in alpha-1-acid glycoprotein results in reduced protein

binding. These changes mean that the dose of alfentanil should be
reduced.
INTRA OPERATIVE MANAGEMENT
• Remifentanil is commonly used intra-operatively, its metabolism by
tissue and plasma esterases (which are preserved in patients with
severe liver disease) means it does not impact on the post-operative
period.

• Surgical traction, positive pressure ventilation, hypocapnia and

pneumoperitoneum can all reduce hepatic blood flow.

• Catecholamine responses are blunted in liver disease further impacting

on cardiovascular stability.
INTRA OPERATIVE MANAGEMENT
• With regards to the choice of volatile agent, isoflurane, sevoflurane
and desflurane all undergo minimal hepatic metabolism.

• Desflurane has the advantage of being least metabolised and

providing the quickest emergence, it also has minimal effect on the
hepatic arterial buffer response and so relatively preserves hepatic
blood flow.
POST OPERATIVE CONCERNS
• Anaesthesia and surgical interventions in patients with significant liver
dysfunction precipitate decompensation.

• Patients with decompensated liver disease are at increased risk of

postoperative hepatic failure, infection, sepsis, bleeding, poor wound
healing and renal dysfunction.

• Hence postoperative critical care management should be considered

for all Childs A, B and C patients.
POST OPERATIVE CONCERNS
• Post operative pain relief can be challenging.

• The role of regional techniques is very much restricted by the high

incidence of coagulation defects. Placement of epidural catheters
should be undertaken with caution and with careful consideration to
timing of catheter removal.

• Similarly, intra-muscular and subcutaneous injections can lead to

haematoma formation and should be avoided.
POST OPERATIVE CONCERNS
• Non steroidal anti-inflammatory medications and their association
with increased risk of GI bleeding, platelet dysfunction and
nephrotoxicity means they are often avoided.

• Paracetamol is sometimes used in this patient group, depending on

the origin of their liver dysfunction, but this should be done with
caution and appropriate monitoring implemented.
POST OPERATIVE CONCERNS
• Fentanyl PCA is generally well tolerated, but accumulation can occur
over time and the patient needs to be nursed in an appropriate
facility, morphine PCA can also be used but a lower bolus dose may be
needed, again to avoid accumulation.
ALGORITHM FOR ANESTHESIA IN
PATIENTS WITH LIVER DISEASE
SO WHAT IS THE PERI OPERATIVE
GOAL IN THESE PATIENTS ??????
HEPATIC BLOOD FLOW AND OXYGEN
DELIVERY SHOULD BE MAINTAINED

TO AVOID ANY FURTHER

HEPATOCELLULAR INJURY AND
RESULTANT DECOMPENSATION