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7/29/2019 LIVER DISEASE IN ANESTHESIA
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Liver Disease and Anaesthesia
Dr R Djagbletey
Department of AnaesthesiaKorle-Bu Teaching Hospital
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Introduction
Anaesthesia and surgery in patients with problems related to theliver cause concern because of the central role of the liver inmany 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 andsurgery may be influenced by hepatic dysfunction.
It is therefore necessary for those practicing anaesthesiaanywhere in the world to have an understanding of liver
function in normal physiology.
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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 thebile 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 andsome other protein factors that are essential for the normalclotting of blood.
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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 drugsused during anaesthesia.
The liver is also central in lipid metabolism withcholesterol and triglycerides synthesised here.
The synthesis and breakdown of glycogen in the liver ispivotal in carbohydrate metabolism.
The liver stores glycogen and releases glucose into theblood when the blood glucose falls for any reason.
The liver is responsible for the biotransformation of drugseither by oxidation or conjugation in order to render themwater-soluble and therefore more easily excreted in theurine or bile.
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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 µmol/l
and defects in cholesterol metabolism together with intra-
hepatic cholestasis may lead to production of poor quality bileand malabsorbtion of fat and fat-soluble vitamins.
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There is reduced synthesis of proteins such as albumin,
clotting factors, thyroid binding globulin and pseudo-cholinesterase.
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 vasoactivesubstances from the damaged liver result in patho-physiological changes in many organ systems
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Cardiovascular changes Vasodilatation and vascular shunting are almost
invariable in ESLD.
Low systemic vascular resistance (SVR) results in highcardiac output and high mixed venous oxygensaturations.
Pulmonary hypertension may develop
while portal venous hypertension can lead to porto-systemic shunting, varices and variceal bleeding.
Variceal bleeding may be life threatening Low flow in the portal vein can result in portal venous
thrombosis..
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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.
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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 bilirubinon the renal tubules or possibly an increased absorptionof endotoxin from the gut.
The key to managing this condition is to avoid it
developing by ensuring adequate hydration and a urineflow of at least 0.75mls/Kg/Hr or 50mls/hr in the averageadult patient.
In most patients with moderately elevated bilirubin this
can be achieved with simple fluid loading for 12 hoursbefore surgery using 0.9% NaCl and during theoperation.
If the urine output is not maintained in this way mannitol10% should be administered until an adequate diuresisis achieved.
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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 besummarised 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.
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Haematological
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.
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Susceptibility to infection
There may be a wide variety of defects in host defences
that can contribute to a substantial risk of sepsis, with upto 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.
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CHRONIC
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
ACUTE
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
CAUSES OF LIVER FAILURE
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Obstructive Jaundice
Biliary obstruction is the most likely cause of jaundice to beencountered by the anaesthetist in the developing world.
It can result from a stone in the common bile duct, pancreatictumour or ascending cholangitis where the bile and biliary treeare infected.
Hepatocellular function is normal (although it may deterioratein 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 vitaminK dependant clotting factors will be reduced, as theabsorption of vitamin K is dependent on the excretion of bilesalts into the small intestine.
The clotting time can, therefore, be prolonged but this can bereadily reversed by parenteral administration of vitamin K.Surgery in these cases is to remove or bypass the obstruction
or to drain infected obstructed bile.
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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 theobese.
The cause of so-called halothane hepatitis is not fully established andmay 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 thecause so given the rarity of the condition, and the limited choice of agents in the developing world, anaesthetists under thesecircumstances should not hesitate to use halothane whenever it isappropriate.
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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.
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In contrast, where there is significant hepatocellular dysfunction
as in advanced cirrhosis or acute hepatitis, drug handling can bedisturbed.
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.
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The liver produces serum cholinesterase, responsible for thebreakdown of suxamethonium, but a reduction of 50% is requiredfor any clinically significant prolongation of the effect of this drug,which is uncommon.
Drugs that are metabolised in the liver may have prolonged half-lives when hepatocellular function is poor.
This may lead to accumulation of drugs given by infusion andwhere 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 effectand neuromuscular blockade should be monitored with aperipheral nerve stimulator
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Examination 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
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Encephalopathy 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
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Child-Pugh Score Points scored
1 2 3Encephalopathy grade none 1-2 3-4
Ascites Absent Mild Moderate to
severe
Bilirubin <35 µmol/l 36-60
µmol/l
>60 µmol/l
Albumin >35 g/l 28-35 g/l <28 g/l
PT (secs prolonged) 1-4 secs 4-6 secs >6 secs
INR [<1-7]] [1.7-2.3] [>2.3]
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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
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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 andplatelets
Sedative premedicants should be avoided in the encephalopathicpatient.
Other drugs may be needed pre-operatively and include antibiotics andH2 receptor antagonists. Delayed gastric emptying is not uncommon.
The oral or intravenous route should be used for administering drugs -intramuscular injections should be avoided.
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Induction 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.
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Neuromascular blocker Atracurium prefered as clearance is independent of liver
metabolism
Analgesia Morphine
Pethidine
fentanyl
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Regional Anaesthesia
Spinal and epidural anaesthesia carries the risk of epidural
haematoma and paralysis if there is abnormal clotting but thereare otherwise no special precautions.
The half-life of lignocaine is prolonged in liver failure but this is
not significant when used in regional anaesthesia.
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Post-operative management
HDU / ICU admission
Monitoring
Supplemental oxygen
Fluids
Analgesia
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THANK YOU
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