Introduction Liver transplantation (LT) is the treatment of choice for end-stage liver disease regardless of its aetiology. Ever since the first transplant interventions in the 1960s, mortality rates after LT have significantly improved and have led to an increase in the number of successful procedures and improved outcomes. Significant challenges remain for the transplant team as the procedure is performed on high-risk patients with impaired cardiovascular, pulmonary, renal and coagulation systems. Recent publications have indicated that transplant candidates are older, sicker and with multiple associate co-morbidities and organ dysfunctions compared to those treated in the past. Adequate perioperative care is essential for a prompt graft function which will improve organ system recovery and recipient’s quality of life [1]. Though there is a potential worldwide liver graft shortage, the expansion of the donor pool using marginal donors and increasing donor age has resulted, never the less, in reduced waiting list mortality [2]. A successful LT requires teams with a particular set of skills and competences, including a complete and detailed understanding of the multi-organic pathophysiology of liver failure and its implications and management during the three stages of surgery. There have been many innovations, updates and procedural changes in the anaesthetic management of patients during this time. This article gives an overview of the current literature regarding anaesthetic management during liver transplantation and its singularities during the three stages of surgery. Go to: Indications for liver transplantation The indications for LT in patients with acute and chronic liver failure should be assessed independent of the aetiology and are listed in Table 1 [3]. Table 1 Indications for liver transplantation Class Disease Non-cholestatic liver disease HepatitisB HepatitisC HepatitisD HepatitisA Alcoholic liver disease Autoimmune hepatitis Cryptogenic cirrhosis Non-alcoholic steatohepatitis Other Cholestatic liver disease Primary biliary cirrhosis Secondary biliary cirrhosis (Caroli disease, choledochal cyst) Primary sclerosing cholangitis Other Malignant disease Hepatocellular carcinoma Cholangiocarcinoma Hepatoblastoma Other Extrahepatic biliary atresia or hypoplasia Alagille syndrome Other Metabolic diseases Alpha-1 antitrypsin deficiency Crigler-Najjar disease, Type I Byler’s disease Glycogen storage disease, Type I Wilson’s disease Hemochromatosis Tyrosinemia Wolman’s disease Familial amyloidotic polyneuropathy Primary hyperoxaluria type 1 Other Hepatic vein thrombosis Budd-Chiari Acute hepatic failure Hepatitis Drugs Unknown aetiology Re-transplantation Primary non-function Hepatic artery thrombosis Acute/chronic rejection Open in a separate window The US and European countries have been using the Model for End-Stage Liver Disease (MELD) score for organ allocation since 2007. This is a grading system from 6 to 40 points, which depen

1. ANAESTHESIA FOR LIVER TRANSPLANTATION
Moderator : Dr. Monu ma’am

2. OVERVIEW
• History
• Types of liver transplantation
• Indications and contraindications
• Criteria for recipient selection
• Pre – op assessment of donor
• Patho-physiology of end stage liver disease
• Pre-operative evaluation of recipient and considerations
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3. INTRODUCTION
• History:
• Liver transplantation is the treatment of choice for end-stage liver disease regardless of the aetiology.
• challenging surgery performed on patients with complex physiology profiles, complicated by multi-
system dysfunction.
• 1963 - Thomas Starzl performed the first human liver transplant in a 3-year-old child with biliary atresia,
died in the operating room from massive hemorrhage caused by venous collaterals and uncontrollable
coagulopathy.
• Four years later, Starzl performed the first successful transplant in an 18-month-old infant with
hepatocellular carcinoma.
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4. • TYPES OF LIVER TRANSPLANTATION:
• Orthotopic liver transplantation:
• Donor liver is transplanted in normal anatomic position in recipient.
• Heterotopic liver transplantation:
• Donor liver is placed within abdominal cavity with patients native organ occupying normal anatomic
position.
• Difficult to accommodate an extra organ in abdomen with complex blood supply.
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5. - Auxillary liver transplantation: - Split liver transplantation:
Implanting healthy liver graft either heterotopically
or orthotopically while leaving all or part of native liver
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6. • Indications : • Contraindications:
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7. • Criteria for recipient selection:
• Two commonly used scoring systems assess the severity of liver dysfunction.
• Child-Turcotte-Pugh (CTP) classification has been used to assess severity in cirrhotic patients and a score of
>6 suggests a short life expectancy.
• In 2002, the MELD score replaced the CTP score for liver allocation.
• Survival based on CTP score:
1 year 2 year
Child A 100% 85%
Child B 80% 60%
Child C 45% 35%
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8. • The Model for End-stage Liver Disease (MELD) score predicts 3 month mortality in patients undergoing TIPS
procedure.
• In 2002, the MELD score replaced the CTP score for liver allocation and is less subjective.
• MELD = 9.57 × loge (creatinine) + 3.78 × loge (total bilirubin) + 11.2 × loge (INR) + 6.43.
• This is a grading system from 6 to 40 points.
• MELD > 15 – eligible for liver transplantation.
• For better predictive accuracy :
• MELD - Na
• Integrated MELD – age & albumin.
• PELD – pediatric patients.
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9. • The decision to list a patient for transplantation is based on severity of hepatic dysfunction than the underlying
aetiology.
• “Standard MELD exceptions” are eligible for an upgrade in MELD points and require periodic reassessment.
• Acute liver failure
• Primary graft dysfunction of a recently transplanted liver
• Hepatocellular carcinoma, cholangiocarcinoma
• Hepatopulmonary syndrome & portopulmonary hypertension.
• Milan criteria - selecting patients with primary liver tumours who may benefit from LT.
• Patients with a single tumour of 5 cm or less, or up to 2–3 tumours between 1 -3cms in diameter, are considered
to qualify for LT
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10. • Peri – operative assessment of living donor:
• To ensure donor safety and provide optimal patient outcome.
• Age – 18 to 55 yrs
• ASA 1 or ASA 2 persons
• Medical, surgical, anaesthetic history,
• Physical examination
• Investigations – complete surgical profile.
• Echocardiography or stress test – patients with CAD risk factors.
• Informed & written consent – anaesthetic procedure & need for postop ventilation.
• Blood & blood products
• Psychological support.
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11. • Pre-operative evaluation of recipient:
• According to UNOS, most deaths occurred within first week following OLTX and most common causes –
cardiovascular disease, operative mortality, primary graft failure and hemorrhage.
• Liver cirrhosis is defined as progressive fibrosis and the formation of regenerative nodules, and is the final
common pathway in which hepatocytes are replaced by connective tissue after various, repetitive insults.
• Impairment of synthetic & metabolic function of liver.
• The amount of remaining functional hepatic mass and the degree of architectural distortion determine the
functional state of the liver.
• Patients with cirrhosis are debilitated with multiorgan dysfunction.
• successful procedure requires an excellent understanding of the patho-physiology of liver failure and its
implications.
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12. • Pathophysiology - Chronic parenchymal inflammation and necrosis
areas of fibrosis and disruption of hepatic architecture
resistance to blood flow in liver
portal hypertension and formation of vascular shunts between portal and systemic veins
• When portal hypertension is severe (pressure gradient between the portal and hepatic veins exceeds 10 to 12
mm Hg), CLD becomes systemic disease and affects nearly every other organ system.
• Complications – ascites
varices
cardiovascular
pulmonary
hepatorenal dysfunction
hepatic encephalopathy
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13. • Pre operative evaluation :
 History of CLD
 Admissions
 Decompensations
 Comorbidities
 Medications
 Addictions
 Infections
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14. • Varices:
• cirrhosis increased inflammation portal HTN increased NO
resistance to splanchnic flow and portosystemic collaterals
rupture of collaterals lethal complication
• Portal hypertension - diagnosed by measurement of wedged hepatic venous pressure (by advancing catheter into
hepatic vein to the wedge position)
• Hepatic venous pressure gradient = WHVP – FHVP
• Normal HVPG = 3-5 mm Hg
• In patients with varices, HVPG > 10-12 mm Hg
• Risk of variceal bleeding depends on size of varices & variceal pressure (HVPG).
• Esophagogastroduodenoscopy - gold-standard for diagnosing varices.
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15. • Primary prophylaxis – Nonselective β-adrenergic blockers
Endoscopic ligation (procedure of choice)
• Management of acute variceal bleeding:
• intravascular volume resuscitation,
• elective intubation of trachea for airway protection,
• correction of severe coagulopathy,
• pharmacologic manipulation of portal pressure – giving splanchnic vasoconstrictors
• endoscopic variceal ligation
• Balloon tamponade for resistant variceal bleeding.
• Definitive therapy – surgical shunts, TIPS , liver transplant.
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16. • Ascites:
• Ascites is the most common complication of cirrhosis leading to hospitalization
• Accumulation of serous fluid in peritoneum.
Cirrhosis causes decrease in plasma volume
excessive renal retention of sodium & water
intravascular volume expands
 plasma oncotic pressure decreases, with the liver unable to produce sufficient albumin
 portal hydrostatic pressure increases
Low oncotic pressure + portal hypertension
formation of edema and ASCITES.
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17. • Tense ascites may decrease functional residual capacity (FRC), affecting pulmonary gas exchange and increase
risk of aspiration.
• Hydrothorax or pleural effusions may produce atelectasis.
• A serum-ascites albumin gradient greater than 1.1 mg/dL indicates portal hypertension.
• Treatment :
• Paracentesis
• Diuretics
• Rule out SBP.
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18. • Cardiovascular complications:
• Hyperdynamic circulation:
 high cardiac output
 low arterial blood pressure hallmark of ESLD
 low systemic vascular resistance
• result of portal hypertension-induced production of vasodilators
such as natriuretic peptides, vasoactive intestinal peptide,
endotoxin, glucagon, and nitric oxide.
• overproduction of vasodilators is responsible for reduced
circulatory responsiveness to sympathetic stimulation.
• results in a need for increased doses of vasopressors
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19. Cirrhotic cardiomyopathy :
 Systolic dysfunction - impaired contractile responsiveness to physiologic or pharmacologic stress,
 Diastolic dysfunction - impaired left ventricular relaxation,
 Electrophysiological changes - with prolonged QT interval
 Cardiac resistance to beta adrenergic stimulation.
 EF < 40% - contraindication to transplant.
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20. • Coronary artery disease:
• All liver transplant waitlist patients should be screened for coronary artery disease (CAD).
• Traditional risk factors
• hypertension,
• smoking,
• diabetes,
• hypercholesterolemia,
• obesity and genetic history.
• These comorbidities are especially likely in patients with nonalcoholic fatty liver disease.
• In patients with multiple risk factors or when noninvasive testing is suggestive of ischemia,
coronary angiography is indicated.
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21. • Arrhythmias :
• Atrial fibrillation
• Supra ventricular tachycardia
• QT prolongations
• Arrhythmias may be aggravated by sympathetic stimulation.
• Acid base and electrolyte abnormalities.
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22. • Assessment of patient’s cardiovascular system:
• History & physical examination
• ECG – ST-T changes
arrhythmias
RAE , RVH
QT prolongation
• Echo – LVEF, RWMA, valve abnormalities
• Stress testing – pharmacological DST
• Coronary angiogram.
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23. • Pulmonary complications:
• 50% to 70% of patients with chronic liver disease complain of shortness of breath.
 Ventilation-perfusion abnormalities –
underlying obstructive airways disease,
fluid retention,
hepatic hydrothorax,
decreased lung capacities secondary to large volume ascites
α-1 antitrypsin deficiency
cystic fibrosis.
 Vascular abnormalities - Hepatopulmonary syndrome (HPS)
Portopulmonary hypertension (PPHTN)
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24. • Hepatic hydrothorax:
• Transmigration of fluid through openings in diaphragm.
• Sum of positive intraabdominal pressure and negative intrathoracic pressure determine the flow.
• Mostly right sided.
• Rule out cardiovascular and pleural causes.
• Signs – cough
dyspnea
hypoxemia
respiratory failure
• Management – reduced salt intake
thoracocentesis
cell count of pleural fluid
antibiotics
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25. • Hepatopulmonary syndrome (HPS)
• Diagnostic criteria –
i. portal hypertension,
ii. PaO2 < 70 mm Hg on room air (alveolar-arterial oxygen gradient >15 mm
Hg),
iii. evidence of intrapulmonary vascular dilation
• increase in pulmonary capillary diameter, from between 8 to 15 μm and 50 to 500
μm.
• This increase, together with hyperdynamic circulation of the cirrhotic patient,
allows insufficient time for oxygen diffusion through the entire stream of capillary
blood.
• Results in incomplete oxygenation of blood. This is correctable with the
administration of oxygen.
• Because IPVDs predominate in the bases of the lungs, standing worsens
hypoxemia compared with the supine position (orthodeoxia).
• Improve with liver transplantation.
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26. • Portopulmonary hypertension:
• defined as pulmonary hypertension in the presence of portal hypertension in a patient without other predisposing
factors.
• diagnostic criteria : (1) clinical evidence of portal hypertension
(2) mean PA pressure of 25 mm Hg at rest or 30 mm Hg during exercise;
(3) mean PA occlusion pressure less than 15 mm Hg or transpulmonary gradient (mean PA pressure minus
wedge pressure) greater than 12 mm Hg;
(4) PVR greater than 240 dyn·s·cm−5
• Mean PA > 50mm Hg – contraindication for transplant.
• patients with moderate or severe PPHTN should undergo treatment
for PPHTN before liver transplantation.
• Treatment – Prostacyclin analogues - Epoprostenol
Endothelin receptor antagonist - Bosentan
PDE 5 inhibitor - Sildenafil
Grading Mean PA
mild 25 - 35 mm Hg
moderate 35 - 50 mm Hg
severe > 50 mm Hg
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27. • Assessment of patient’s pulmonary system:
 Pulse oximetry for screening of HPS
 Chest radiography
 Arterial blood gas analysis
 Pulmonary function tests
 ECG – right atrial enlargement or right ventricular hypertrophy
 Echocardiography for POPH – RVSP > 45mm Hg - Right heart catheterisation
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28. • Renal dysfunction (Hepatorenal syndrome):
• is due to renal hypoperfusion and retention of sodium.
• prerenal abnormality caused by circulatory derangements of advanced cirrhosis.
• Pathophysiology - local production of vasodilators - nitric oxide
Splanchnic vasodilation
decrease in the effective circulating blood volume and arterial blood pressure,
activates sympathetic, renin-angiotensin-aldosterone, and vasopressin systems
severe reduction in renal perfusion and glomerular filtration
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29. • Diagnosis –
• Treatment –
• Vasoconstrictor therapy targeting underlying splanchnic vasodilation
• Vasopressin, terlipressin
• somatostatin
• Norepinephrine
• Volume expansion by albumin
• Definitive therapy – renal replacement therapy
liver transplantation.
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30. • Hepatic encephalopathy:
• Chronic liver dysfunction - accumulation of neurotoxins such as
ammonia, short chain fatty acids, and mercaptans.
• Their metabolism is impaired in liver dysfunction. These toxins can
bypass the liver via portosystemic shunts.
• In the central nervous system, ammonia is metabolized to glutamine.
Glutamine increases intra-cellular osmolality and can lead to cerebral
edema.
• Benzodiazepines should be used with care because they may potentiate
this encephalopathy and precipitate hepatic coma.
• Treatment –
• Look for precipitating causes
• nonabsorbable disaccharide lactulose
• nonabsorbable antibiotics - rifaximin can reduce bacterial production
of ammonia
• L- ornithine L- aspartate
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31. • Acute management of hepatic encephalopathy consists of early intubation for airway protection to prevent
aspiration, maintain oxygenation, and prevent hypercarbia.
• Mild hypocapnia and mild hypothermia may be helpful for neuroprotection.
• Monitoring and evaluating patients fluctuation in consciousness and cognition can be graded using West Haven
criteria.
• In order to exclude pre-existing disease – EEG & CT scan are recommended.
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32. • Coagulopathy:
• Liver synthesizes thrombopoietin, procoagulant and anticoagulant factors, with exception of tissue thromboplastin
(III), calcium (IV), and von Willebrand factor (VIII)
• also the site for clearance of activated factors.
• Coagulation dysfunction in liver disease can better be described
as a fragile balance between low levels of both procoagulation
and anticoagulation factors.
• During LT, both bleeding as well as thromboembolic
complications may occur
• Thrombocytopenia
- splenic sequestration in the setting of portal hypertension
- impaired hepatic synthesis of thrombopoietin.
• Fibrinolysis due to decreased clearance of plasminogen activators (tPA)
• Disseminated intravascular coagulation – hypercoagulable state due to inadequate clearance of activated clotting
factors & decreased coagulation inhibitors.
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33. • Tests for hemostatic status:
 Bleeding time
 Prothrombin time
 Activated partial thromboplastin time
 Platelet count
 Thromboelastography –
• quality of clot formation (generation of thrombin)
• clot strength (the effect of fibrinogen and platelets)
• fibrinolysis
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34. • Metabolic abnormalities:
• Acid – base abnormalities –
• Respiratory alkalosis with metabolic acidosis
• Respiratory acidosis in patients with HE
• Electrolyte abnormalities –
• Sodium
• Potassium
• hypomagnesemia
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35. • Pre operative considerations:
- Hematological - Cardiovascular -Respiratory
• Hb ECG pulse oximetry
• TLC, DLC ECHO chest x-ray
• Platelet count DST ABG
• Bleeding & clotting time CAG PFT
• PT, aPTT, INR ECG & ECHO
• TEG
• Liver function tests – liver enzymes, albumin, bilirubin
• Renal function tests – serum urea, creatinine
• Blood cultures
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