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Liver Disease and Anaesthesia

Dr R Djagbletey
Department of Anaesthesia Korle-Bu Teaching Hospital

Anaesthesia and surgery in patients with problems related to the liver cause concern because of the central role of the liver in many of the body's metabolic and synthetic functions. The process of anaesthesia may adversely effect these functions and equally the patient's response to anaesthetic drugs and surgery may be influenced by hepatic dysfunction. It is therefore necessary for those practicing anaesthesia anywhere in the world to have an understanding of liver function in normal physiology.

Functions of the liver

The liver conjugates bilirubin, produced from the degradation of the haemoglobin of red cells This now water-soluble form of bilirubin is then excreted into the bile ducts and thence into the small intestine.

Also passed to the gut are the bile salts produced by the liver and necessary for the absorption of the fat-soluble vitamins A, D, E and K.
Vitamin K is essential for the production of prothrombin and some other protein factors that are essential for the normal clotting of blood.

Synthesis of many proteins takes place in the liver including most clotting factors and many carrier proteins, such as albumin, which to a varying degree bind drugs used during anaesthesia.

The liver is also central in lipid metabolism with cholesterol and triglycerides synthesised here.
The synthesis and breakdown of glycogen in the liver is pivotal in carbohydrate metabolism. The liver stores glycogen and releases glucose into the blood when the blood glucose falls for any reason.

The liver is responsible for the biotransformation of drugs either by oxidation or conjugation in order to render them water-soluble and therefore more easily excreted in the urine or bile.

Impaired liver function

Impaired liver function gives rise to effects directly attributable to the failing liver itself and also to indirect effects expressed via other organ systems. Effects directly attributable include hypoglycaemia, lactic acidosis, azotemia and impaired urea synthesis. Jaundice appears when serum bilirubin exceeds 35 mol/l and defects in cholesterol metabolism together with intrahepatic cholestasis may lead to production of poor quality bile and malabsorbtion of fat and fat-soluble vitamins.

There is reduced synthesis of proteins such as albumin, clotting factors, thyroid binding globulin and pseudocholinesterase. Impaired hormone biotransformation, reduced production of modulator proteins and reduced protein binding lead to increased circulating levels of hormones such as insulin, thyroxine, T3, aldosterone and oestrogen. Impaired hormone modulation, failure to clear by-products of metabolism, activation of cytokines and release of vasoactive substances from the damaged liver result in pathophysiological changes in many organ systems

Cardiovascular changes

Vasodilatation and vascular shunting are almost invariable in ESLD. Low systemic vascular resistance (SVR) results in high cardiac output and high mixed venous oxygen saturations. Pulmonary hypertension may develop while portal venous hypertension can lead to portosystemic shunting, varices and variceal bleeding. Variceal bleeding may be life threatening Low flow in the portal vein can result in portal venous thrombosis..

Pulmonary changes

Pulmonary problems are both vascular and mechanical. Intra- pulmonary shunt dilatation (hepato-pulmonary syndrome) Impaired hypoxic vaso-constriction and ventilation perfusion mismatch lead to arterial desaturation and clubbing if chronic. Pleural effusions together with ascites can cause considerable mechanical embarrassment of respiration and a reduction in functional residual lung capacity

Electrolytes and Renal

There are numerous causes of renal impairment in liver failure, including hepato-renal syndrome

sepsis and renin-angiotensin activation.

Hypoalbuminaemia and oedema are common.

Hepato-renal Syndrome

It may be related to pre and peroperative dehydration and hypovolaemia, falls in renal blood flow during surgery, a direct effect of the excess conjugated bilirubin on the renal tubules or possibly an increased absorption of endotoxin from the gut. The key to managing this condition is to avoid it developing by ensuring adequate hydration and a urine flow of at least 0.75mls/Kg/Hr or 50mls/hr in the average adult patient. In most patients with moderately elevated bilirubin this can be achieved with simple fluid loading for 12 hours before surgery using 0.9% NaCl and during the operation. If the urine output is not maintained in this way mannitol 10% should be administered until an adequate diuresis is achieved.

Neurological problems

Mechanisms leading to deepening encephalopathy, loss of vascular auto-regulation, cerebral oedema and death are incompletely understood. A number of processes may act in parallel, but can be summarised as the accumulation of neurotoxic compounds penetrating an impaired blood-brain barrier. At the same time, lack of nutrients and substrates may impair brain metabolism and alter neuro-transmitter synthesis.


Anaemia may be the result of nutritional deficiency, toxic bone marrow depression or gastrointestinal bleeding from varices or erosions. Coagulation defects arise from thrombocytopenia, platelet dysfunction and decreased levels of circulating clotting factors. Clotting factor levels fall because of impaired synthesis, vitamin K malabsorbtion and intravascular consumption. The short half-life of clotting factors means that INR or Prothrombin Ratio (PTR) can reliably be used to evaluate residual hepatic function.

Susceptibility to infection

There may be a wide variety of defects in host defences that can contribute to a substantial risk of sepsis, with up to 80% of patients with Fulminant Hepatic Failure developing bacterial sepsis (frequently Gram positive organisms) and 30% fungal sepsis.

Clearly, particular attention must be paid to aseptic technique when inserting lines.



Infection Viral A-E, Non A-E Drugs e.g. paracetamol, rifampicin, phenytoin, halothane Toxins Amanita phalloides Miscellaneous Wilson's Disease Fatty liver of pregnancy HELLP Lymphoma Sepsis Reye's syndrome Heatstroke

Infection Viral A-E, Non A-E Drugs e.g. paracetamol, rifampicin, phenytoin, halothane Toxins Amanita phalloides Miscellaneous Wilson's Disease Fatty liver of pregnancy HELLP Lymphoma Sepsis Reye's syndrome Heatstroke

Obstructive Jaundice

Biliary obstruction is the most likely cause of jaundice to be encountered by the anaesthetist in the developing world. It can result from a stone in the common bile duct, pancreatic tumour or ascending cholangitis where the bile and biliary tree are infected. Hepatocellular function is normal (although it may deteriorate in prolonged obstruction) so the excess plasma bilirubin is chiefly conjugated. As conjugated bilirubin is water-soluble it will be excreted in the urine which becomes dark. Stools are pale as a result of poor lipid absorption. Although protein synthesis is normal, the production of vitamin K dependant clotting factors will be reduced, as the absorption of vitamin K is dependent on the excretion of bile salts into the small intestine. The clotting time can, therefore, be prolonged but this can be readily reversed by parenteral administration of vitamin K. Surgery in these cases is to remove or bypass the obstruction or to drain infected obstructed bile.

Halothane and Jaundice

It was discovered that some adult patients can,very rarely, become jaundiced from severe hepatic damage after a second halothane anaesthetic. The incidence of this halothane hepatitis in adults is thought to be 1:7000-30,000 halothane anaesthetics. It is even rarer in paediatric patients and with the newer volatile agents. The risk is thought to be higher in women, the middle aged and the obese. The cause of so-called halothane hepatitis is not fully established and may be multifactorial. Factors inplicated toxic metabolites immunological cause. Reduced hepatic blood flow and hypoxia In most cases of post operative jaundice halothane is unlikely to be the cause so given the rarity of the condition, and the limited choice of agents in the developing world, anaesthetists under these circumstances should not hesitate to use halothane whenever it is appropriate.

In biliary obstruction There is no significant alteration in drug handling and Normal doses of thiopentone, opiates, benzodiazepines and muscle relaxants are given. Although the nondepolarising muscle relaxant vecuronium is partly cleared through the bile, the normal rapid uptake by the liver cells is unchanged and there is no effect on the half-life.

In contrast, where there is significant hepatocellular dysfunction as in advanced cirrhosis or acute hepatitis, drug handling can be disturbed. Decreased synthesis leads to lowered levels of carrier proteins in the blood. This means that for the same dose of a highly protein bound drug, such as thiopentone, there will be a greater level of unbound and therefore active drug. Smaller doses are required.

The liver produces serum cholinesterase, responsible for the breakdown of suxamethonium, but a reduction of 50% is required for any clinically significant prolongation of the effect of this drug, which is uncommon. Drugs that are metabolised in the liver may have prolonged halflives when hepatocellular function is poor. This may lead to accumulation of drugs given by infusion and where drugs given in repeat or top up doses, such as muscle relaxants, the interval between doses should be prolonged. Ideally drugs such as induction agents should be titrated to effect and neuromuscular blockade should be monitored with a peripheral nerve stimulator

Aetiology. Previous anaesthetic history CVS: exercise tolerance, oedema, orthopnoea RS: dyspnoea, ascites / pleural taps GI: bleeding, haematemesis, maelaena, piles Sepsis / urine output Medication:diuretics / antibiotics

Palor, jaundice, fever, cyanosis, oedema clubbing, temperature,muscle mass
CVS: pulse rate, venous pressure, BP RS: resp. rate, effusions, sputum Abdo: ascites, spleen, caput medusae CNS grade of consciousness ICP: unconscious patient

Grade 1: mild confusion, fully coherent when roused
Grade 2: increasing confusion, arousable,able to be rational Grade 3: sleeping mostly, roused to command, may be agitated or aggressive

Grade 4: unrousable, reacts to pain, ?signs of cerebral oedema


Full Blood count BUE & Cr GXM Blood and FFPs Blood sugar LFTs ECG CXR Clotting Profile Blood - electrolytes, sugar, albumin, creatinine, gas, SpO2, lactate, INR (PTR) Viral serology; Ultrasound - abdominal (portal flow, pressure, ascites) AND cardiac (myocard wall movement, pericardial effusion) Endoscopy, Microbiology

Child-Pugh Score
Points scored

Encephalopathy grade Ascites

1-2 Mild

3-4 Moderate to severe >60 mol/l <28 g/l >6 secs [>2.3]

none Absent

Bilirubin Albumin PT (secs prolonged) INR

<35 mol/l >35 g/l 1-4 secs [<1-7]]

36-60 mol/l 28-35 g/l 4-6 secs [1.7-2.3]

Child-Pugh A Score < 6, Child-Pugh B Score 7-9, Child-Pugh C Score >10

Medium risk patients - Child-Pugh Group A High risk patients - Child-Pugh Group B/C

Pre-operative preparation

Adequate hydaration 1L 5% dextrose/ day for 2 days prior to surgery IV Vit K 10mg daily at least 5 days prior to surgery Coagulopathy may require correction with fresh frozen plasma and platelets Sedative premedicants should be avoided in the encephalopathic patient. Other drugs may be needed pre-operatively and include antibiotics and H2 receptor antagonists. Delayed gastric emptying is not uncommon. The oral or intravenous route should be used for administering drugs intramuscular injections should be avoided.


Reduced doses in hepatic dysfunction Propofol is a useful induction agent as it undergoes considerable extra-hepatic Thiopentone Ethomidate

Inhalational agents

Isoflurane prefered as it preserves hepatic blood flow

sevoflurane and desflurane are acceptable.

Neuromascular blocker

Atracurium prefered as clearance is independent of liver metabolism


Morphine Pethidine fentanyl

Regional Anaesthesia

Spinal and epidural anaesthesia carries the risk of epidural haematoma and paralysis if there is abnormal clotting but there are otherwise no special precautions. The half-life of lignocaine is prolonged in liver failure but this is not significant when used in regional anaesthesia.

Post-operative management

HDU / ICU admission Monitoring Supplemental oxygen Fluids Analgesia