Anaesthesia for hepatic

transplantation
Dawn Fabbroni MBChB MRCP FRCA
Mark Bellamy MBBS MA FRCA

Liver transplantation has become the treat-
ment of choice for end-stage liver failure and
some cases of acute liver failure. This can be
orthotopic (same place) or heterotopic (other
place). The first successful orthotopic liver
transplant was performed by Starzl in 1963.
Since then, advances in surgical, anaesthetic
and immunological management have resul-
ted in prolonged graft survival and overall
(MELD) score and paediatric end-stage liver Key points
disease (PELD) scores.2 The MELD/PELD
Liver transplantation is the
scores are numerical scales based on the
treatment of choice for end-
patient’s risk of dying while awaiting trans- stage liver failure.
plantation. The MELD score for patients
older than 12 yr is based on bilirubin, inter-
Pre-assessment and careful
patient selection should be
national normalized ratio (INR) and creatin-
performed by a
ine. The PELD score is based on bilirubin, multidisciplinary, anaesthetic,
INR albumin, growth failure and age when

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surgical and hepatology team.
1 yr survival rates >80%.1 Liver transplanta- listed. Indicators of poor prognosis include
There are three phases in the
tion is performed in patients of all ages. renal impairment, hyponatraemia, muscle
physiology of a transplant
Paediatric liver transplantation has a 10 yr wasting, impaired cardiopulmonary function (resection or ‘pre-anhepatic’
survival rate of 80–90%. Good success rates and severe pulmonary hypertension. Mild phase, anhepatic phase and
are also seen in the >70-yr-old population, to moderate pulmonary hypertension (mean post-reperfusion phase).
providing they are carefully selected to take <35 mm Hg) is not a contraindication to These must be understood
account of co-morbidities.1 transplantation; however, mortality increases and managed appropriately.
to around 100% in severe pulmonary hyper- Blood loss is unpredictable; it
Indications for liver tension (mean pulmonary artery pressure can be insignificant or massive.
transplantation >50 mm Hg). New proven hepatopulmonary
Perioperative care should be
syndrome (triad of liver disease, hypoxaemia provided in an appropriate
Indications for liver transplantation include on room air and pulmonary vascular level 3 facility.
chronic progressive liver disease (predomin- dilatation) is not a contraindication to liver
antly, but not exclusively, cirrhosis) and acute transplantation as it may resolve after suc-
hepatic failure (Table 1). The decision to list cessful grafting in a high proportion of cases.3
a patient for transplantation is based more Transplantation for primary hepatobiliary
on the severity of hepatic dysfunction than malignancy is considered in the absence of
the underlying aetiology. Priority is based on metastasis and based on tumour bulk; how-
specific prognostic criteria using a number ever, results are poor (25–40% 2 yr survival).
of scoring systems. Commonly used scores Selection is based on either the ‘Milan
include the model for end-stage liver disease criteria’ (single tumour
5 cm or up to three
Table 1 Indications for orthotopic liver transplantation1 tumours, none >3 cm)4 or the San Francisco
criteria (single lesion
6.5 cm or up to 3
Cirrhotic disease
Virus-related cirrhosis lesions, none >4.5cm and total tumour
Dawn Fabbroni MBChB MRCP FRCA
Alcoholic cirrhosis diameter
8 cm).
Primary biliary cirrhosis
Specialist Registrar in Anaesthesia
Cryptogenic cirrhosis
St James’s University Hospital
Autoimmune hepatitis Preoperative assessment Beckett Street
Cancers
Leeds
Hepatocellular carcinoma A multidisciplinary preoperative assessment LS9 7TF
Cholangiocarcinoma should be performed by a hepatologist, UK
Biliary tract carcinoma surgeon and anaesthetist before listing for Mark Bellamy MBBS MA FRCA
Metastases
Cholestatic disease transplantation. Assessment involves evaluat- Consultant in Anaesthesia and
Acute hepatic failure ing hepatic dysfunction and associated patho- Intensive Care
Metabolic disease St James’s University Hospital
physiological complications and existing Beckett Street
Wilson’s Disease
Haemochromatosis concomitant disease. Leeds
Other LS9 7TF
Budd–Chiari syndrome UK
Preoperative investigations Tel: 0113 206 6813
Benign liver tumours
Failure of previous transplant Fax: 0113 206 4141
A number of investigations are used to esta- E-mail: m.c.bellamy@leeds.ac.uk
(rejection, primary non-function)
blish cardiovascular fitness and risk profile. (for correspondence)

doi:10.1093/bjaceaccp/mkl040
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006 171
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Anaesthesia for hepatic transplantation
As a minimum, an ECG and echocardiography should be
performed in all patients. Underlying ischaemic heart disease
and alcohol-related cardiomyopathy are not uncommon, so full
functional assessment is often required. The assessment regimen
varies between centres. Dobutamine stress echocardiography
and cardiopulmonary exercise testing show promise as indicat-
ors of perioperative risk. Exercise ECG, echocardiography and
radionucleide angiography may assist in identifying patients
with significant ischaemic heart disease or cardiomyopathies and
quantifying their risk of undergoing liver transplantation.
Chest X-ray and pulmonary function tests may reveal
existing lung pathology and pleural effusions. They allow
measurement of a patient’s respiratory reserve and can assist
planning ventilatory management after operation. Formal
pulmonary artery catheter studies are performed in patients
suspected of pulmonary hypertension. Up to 10% of patients
with cirrhosis suffer pulmonary hypertension, often in associ-
ation with portal hypertension.
Hyponatraemia is commonly associated with portal hyper-
tension and ascites as a result of water retention. A serum
sodium <125 mmol litre1 is carefully corrected preoperatively
over days or weeks to reduce the risk of pulmonary oedema and
central pontine myelinolysis associated with acute periopera-
tive sodium shifts. This is achieved through fluid restriction
and use of the aldosterone antagonist, spironolactone.
Hypoalbuminaemia, coagulopathy and thrombocytopenia
are not generally corrected preoperatively except where there
is a specific indication (e.g. active bleeding). There appears to be
relatively little relationship between coagulopathy and intra-
operative blood loss. However, increased perioperative blood
loss is associated with portal hypertension and previous surgery
resulting in higher complication and mortality rates.5
In end-stage liver disease, the hepatorenal syndrome results
in renal impairment and ultimately failure. Albumin and
terlipressin are protective in those with or at risk of hepatorenal
syndrome.6 Perioperative haemofiltration may be required.
Intraoperative management
Premedication
Benzodiazepine premedication appears safe in elective cases
but should be avoided in patients with hepatic encephalopathy.
Monitoring
Routine monitoring ECG, oxygen saturations (SpO2) and non-
invasive blood pressure (NIBP) are established before induction.
Further invasive cardiovascular monitoring may be established
either pre- or post-induction depending on the cardiovascular
stability of the patient. Pulmonary artery flotation catheters,
PiCCO and LIDCO and transoesophageal echocardiography
(TOE) are all used in different centres. TOE is the gold standard
and provides continuous information on ventricular wall motion
172 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006
and embolic phenomena. A nasogastric tube, urinary catheter
and oesophageal temperature probe are inserted. Patients at
risk of raised intra-cranial pressure (ICP) (e.g. fulminant liver
failure) are generally transferred from ICU with ICP monitoring
in situ.
Positioning
The patient is positioned supine with one or both arms abducted
to a maximum of 70 . Abduction beyond this angle can result in
brachial plexus injury. A warming hot air overblanket is used.
The lower chest and abdomen are exposed for surgical access.
Induction of anaesthesia
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An i.v. crystalloid infusion is commenced before induction
and continued as maintenance fluid. The main requirement of
induction is cardiovascular stability. A variety of induction
agents are used in different centres. Increasing interest in early
extubation has lead to the use of shorter-acting drug combina-
tions, including midazolam, propofol and remifentanil.
Maintenance of anaesthesia
After intubation, IPPV is established with a suitable volatile
agent, for example desflurane 4.0–6.5% end-tidal concentration
in oxygen-enriched air. Desflurane has the advantage of a quick
recovery time and low hepatic metabolism. Many centres use
either isoflurane or sevoflurane. Nitrous oxide is avoided to
reduce cardiovascular depression, gut distension and bubble
formation if on veno-venous bypass (VVB). Total i.v. anaesthe-
sia with propofol has been used successfully, but may be
associated with cardiac depression after reperfusion.
A remifentanil infusion (0.05–0.3 mg kg1 min1) provides
intraoperative analgesia with the advantage of a very short
context-sensitive half-life. Alternatives include alfentanil infu-
sion or boluses of morphine. Muscle relaxation with atracurium
(at 30 mg h1) provides adequate relaxation and reliable reversal
after prolonged use. Most relaxants are safe provided neuro-
muscular block is monitored to prevent delayed recovery.
I.V. fluids and blood products
Large bore cannulae are required for rapid transfusion of blood
and fluids. A 3–5 lumen central line is inserted under ultrasound
guidance, including a wide bore port (8G). An alternative is
to use two large bore peripheral cannulae (8F). Where VVB is
used, 18 Fr cannulae are inserted percutaneously into an internal
jugular and femoral vein.
A rapid infusion system (e.g. ‘Level-1’) allows rapid transfu-
sion of warmed fluids (37–38 C) at rates of up to 1500 ml min1.
Fresh frozen plasma (FFP), colloid and electrolyte solutions
are used with packed red cells to achieve a haematocrit of
0.26–0.32. FFP, cryoprecipitate and platelet infusions are
administered if required according to measures of coagulopathy
 Anaesthesia for hepatic transplantation

Table 2 Summary of surgical and anaesthetic aspects of liver transplantation

Surgical details Anaesthetic problems Anaesthetic management

Phase I Inverse T or ‘Mercedes’ incision Haemorrhage may occur from

Dissection of the structures around the liver
and porta hepatis, achieving mobilization
Phase II Division of hepatic artery, portal vein and bile
anhepatic duct. The vena cava is cross-clamped both at
phase the diaphragm and immediately below the liver.
or the hepatic vein isolated,
With or without veno-venous bypass
The liver and portion of vena cava is removed
New liver inserted. Caval and portal
anastomoses fashioned
Phase III Blood re-enters the portal vein and caval
reperfusion clamps are removed
phase Hepatic artery is anastomosed and biliary
system reconstructed
dissection, varices and adhesions
Cardiovascular instability from ascitic
decompression
Worsening coagulopathy. No production
of clotting factors, fibrinogen deficiency.
Thrombocytopenia
Absent citrate/lactate metabolism,
reduced gluconeogenesis and glucose
uptake, worsening acidosis
Hypotension and #SVR
Initial Kþ increase then decrease as
graft takes up Kþ
Metabolic acidosis begins to correct
Fibrinolysis prevented/attenuated by
antifibrinolytics (e.g. aprotinin or
tranexamic acid)
Methylprednisolone 10 mg kg1 before
reperfusion to protect against graft
dysfunction and renal injury
10 mmol CaCl2 immediately before reperfusion to
protect the myocardium from "Kþ.
Epinephrine (25–50 1mg) boluses with or without
infusions of vasopressor or inotropic support

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Kþ supplementation after the initial plasma increase

and clinical bleeding. The rationale for the target haematocrit is
to allow adequate oxygen delivery but to prevent hepatic artery
thrombosis. Many centres use thrombo-elastography (TEG),
Sonoclot or other near patient analysers to guide their
management.
Monitoring of full blood count, clotting, electrolytes and
blood gases is carried out hourly or as clinically indicated.
This guides management of ventilation, calcium and potassium
supplementation, glycaemic and acid–base management, and
blood replacement therapy. Occasionally 10–50% dextrose may
be required to treat hypoglycaemia; this is more likely to occur
in cases of severe acute liver failure.
Surgery falls into three phases (Table 2). Each of the three
phases of liver transplantation poses particular problems for
the anaesthetist.
Phase I (pre-anhepatic)
The surgical approach normally utilizes an inverse
‘Mercedes’ incision. Dissection may be complicated by
and sometimes rapid haemorrhage caused by varices
abdominal wall or adhesions within the abdominal
Fluid shifts may result from ascitic decompression.
Phase II (anhepatic phase)
During the anhepatic phase, there is further physiological
derangement. No hepatic clotting factors are produced, fibrino-
gen is deficient and anti-thrombin concentrations decrease,
leading to worsening coagulopathy and the onset of fibrinolysis.
Thrombocytopenia can develop owing to massive blood
transfusion and platelet consumption, exacerbating preoperative
thrombocytopenia. Fibrinolysis may be prevented or attenuated
by antifibrinolytic agents, such as aprotinin and tranexamic
acid.7
Absent citrate and lactate metabolism results in progressive
acidosis. Hypocalcaemia because of citrate accumulation is
treated by slow i.v. calcium infusion. Ionized calcium should be
maintained between 0.84 and 1.4 mmol litre1 to prevent
coagulopathy and cardiac depression. Magnesium may also
need to be supplemented. There is also reduced gluconeogenesis
and glucose uptake. Protection from gastrointestinal tract
antigens is lost.
Phase III (reperfusion phase)
On reperfusion of the preserved liver there is a sudden massive
release of cold, hyperkalaemic, acidotic fluid into the circula-
tion. CaCl2 is given to prevent potassium related arrhythmias.
Before reperfusion, methyl prednisolone 10 mg kg1 is also given
as a slow i.v. infusion as immunosuppression and to protect
against ischaemia-reperfusion injury.
After reperfusion, there is often systemic vasodilatation and
myocardial depression leading to haemodynamic instability.
Excessive hypotension or decrease in cardiac output requires
small boluses of epinephrine (25–50 mg). A rising central venous
T or pressure may contribute to venous congestion in the graft. Post-
steady reperfusion syndrome (PRS) is defined as a reduction in mean
in the arterial pressure (MAP) of 30% occurring within 5 min of graft
cavity. reperfusion and persisting at least 1 min. This is thought to be
mediated by cytokines, vasoactive substances released by the
reperfused liver and activation of complement. Exposure to the
VVB circuit may increase inflammatory cytokines and increase
the incidence of PRS. Hypotension associated with a low
systemic vascular resistance (SVR) may persist for >1 h.
Patients with concomitant cardiac disease, ongoing bleeding or
vasodilatation may require vasopressor or inotropic support.
After the initial increase in serum Kþ, the functioning graft
avidly takes up potassium, so some patients may require
aggressive potassium supplementation for several hours. Meta-
bolic acidosis begins to correct with restoration of lactate
metabolism and bicarbonate production. Primary non-function
or delayed function of the graft (up to 10% of cases) is indicated
by ongoing metabolic acidosis, coagulopathy and absence of
bile production. Most cases require urgent re-transplantation.

Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006 173
Anaesthesia for hepatic transplantation
Cell saver
The introduction of cell salvage techniques has decreased blood
transfusion requirements. Lost red blood cells are scavenged via
a suction tube, heparinized as they enter the cell saver reservoir,
washed with normal saline, centrifuged and stored directly in a
blood bag ready to be re-infused. Contraindications include
malignant aetiology and infected ascitic fluid.
VVB
Depending on the surgical technique, the portal vein, hepatic
artery and the inferior vena cava, above and below the liver,
may be clamped. This results in a dramatic reduction in the
cardiac filling and cardiac output. The degree of haemodynamic
instability is dependent on cardiovascular reserve and the extent
of collateral veins (azygous, superficial abdominal and epidural
veins). Cirrhotic patients tend to tolerate clamping better than
expected owing to established collaterals. MAP is usually
maintained for up to 1 h because of increased heart rate and a
compensatory increase in SVR. The decreased venous return
after cross-clamping may necessitate high volume infusions or
vasopressor use during caval cross-clamping. Relative volume
overload can occur on caval declamping and right heart
dysfunction can result. High systemic venous pressure on cross-
clamping can reduce renal and splanchnic blood flow and
increase portal pressure, resulting in gut oedema and increased
bleeding.
VVB was introduced to limit haemodynamic instability and
other problems encountered on cross-clamping. It involves an
extracorporeal circuit, removing blood from below the cross-
clamp (from femoral or inferior mesenteric veins) via heparin
bonded tubing to a centrifugal pump. The blood is returned
via a central vein (internal jugular or axillary). Early circuits
required systemic heparinization but were abandoned because
of uncontrolled bleeding. A flow equivalent to 20% of cardiac
output is achieved through the bypass circuit. Adding portal
bypass increases flow to about 40% of cardiac output
(3–4 litres min1). Flow in the circuit is produced by a pressure
of 30–50 mm Hg in the clamped IVC and negative pressure
produced by the pump. Haemodynamic stability is improved,
and the need for acute volume loading reduced by around
3 litres.8
Complications of bypass can result from the bypass circuit
or venous access. They are uncommon but there is potential
for hypothermia, air embolism, clot formation, fragmentation of
red cells and failure of the system. Complications from vascular
access include haematoma, major vascular injury, nerve injury,
air embolism and vessel thrombosis.
There is little consensus between different centres when to
use VVB. Some use bypass routinely, while others only on
selective cases. With an overall complication rate of 1 in
350 cases (related to vascular injury and embolism), there is a
strong case for using VVB selectively, that is borderline cardiac
or renal function and portal hypertension where excessive
174 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006
bleeding or prolonged surgery increases the potential for gut
oedema.
Postoperative care
Transplant recipients require intensive care after operation.
While some patients are suitable for early on-table extubation,9
most will undergo a period of ventilation for a few hours.
Patients are initially kept sedated with propofol and either
alfentanil or remifentanil infusions until ready to extubate. This
allows time to achieve normothermia, correction of metabolic
acidosis and ensure haemodynamic stability. The sickest patients
may require prolonged ICU management.
Specific issues in liver transplant recipients include close
monitoring of potassium concentrations as this may require
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ongoing supplementation for 24–36 h. Tight glycaemic control
is achieved with a sliding scale insulin infusion. Coagulation
tests and full blood count guide further transfusion of blood
and blood products. The haematocrit is maintained between
0.26 and 0.32. Higher levels are associated with an increased
incidence of hepatic artery thrombosis and graft failure.10 In
patients with known hypercoagulable states (Budd–Chiari,
Protein C and S deficiency), anticoagulation with heparin is
required and haematocrit maintained at the lower end of the
range. Some centres use prophylactic low-dose heparin to
prevent hepatic artery thrombosis. Immunosuppression is
commenced early in the postoperative period. Patient-controlled
analgesia or a morphine infusion is used for postoperative pain
relief.
Paediatric liver transplantation
The principles of liver transplantation in children are similar,
but with a few important differences. The major aetiology in
paediatric practice is predominantly biliary cirrhosis secondary
to biliary atresia. Other causes include inborn errors of meta-
bolism, cystic fibrosis and hepatoblastomas.
Small children present their own problems. The donor graft
is often a reduced graft from an adult liver (left lateral segment
or left lobe). The large raw liver surface is sealed with fibrin glue
and has the potential for major haemorrhage. Meticulous
surgical technique is required as a smaller circulating volume
means that even small bleeds can lead to significant blood loss.
Cell salvage is rarely used as the volume of blood loss is not
adequate to use the technique. VVB cannot be used in children
<35–40 kg as there is inadequate flow through the small
cannulae. There is a risk of overloading patients because of fluid
administration during cross-clamping but paediatric patients
tend to be more haemodynamically stable. The vessel calibre of
patients and the donor graft is much smaller in children,
enhancing the risk of hepatic artery thrombosis and graft failure.
Blood and blood products are used cautiously; antifibrinolytics
are usually avoided. The haematocrit is maintained at <0.30,
haemoglobin of 8 g dl1 and serum sodium <140 mmol litre1.

In smaller patients, heparin in flush lines plus release of
endogenous heparin can produce a coagulopathy, demonstrated
by a ‘straight’ TEG. Protamine may be required.
In our centre, most children are extubated at the end of
surgery. However, some continue sedation and ventilation for a
short period. Most require to be in ICU for 24–48 h.
Key References
1. European Liver Transplant Registry 1998–2003. Available at: http://www.
eltr.org
2. Freeman RB, Harper A, Edwards EB. Excellent liver transplant survival
rates under the MELD/PELD system. Transplant Proc 2005; 37: 585–8
3. Mandell MS. Hepatopulmonary syndrome and portopulmonary hyperten-
sion in the model for end-stage liver disease (MELD) era. Liver Transpl
2004; 10 (10 suppl 2): S54–8
4. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the
treatment of small hepatocellular carcinomas in patients with cirrhosis.
N Engl J Med 1996; 334: 693–9
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006
Anaesthesia for hepatic transplantation
5. Massicotte L, Sassine MP, Lenis S, Seal RF, Roy A. Survival rate changes
with transfusion of blood products during liver transplantation. Can J
Anaesth 2005; 52: 148–55
6. Danalioglu A, Cakaloglu Y, Karaca C, et al. Terlipressin and albumin
combination treatment in hepatorenal syndrome. Hepatogastroenterology
2003; 50 (suppl 2): ccciii–cccv
7. Xia VW, Steadman RH. Antifibrinolytics in orthotopic liver transplanta-
tion. Liver Transpl 2005; 11: 10–18
8. Reddy K, Mallett S, Peachy T. Venovenous bypass in orthotopic liver
transplantation: time for a rethink? Liver Transpl 2005; 11: 741–9
9. Mandell MS, Lezotte D, Kam I, Zamudio S. Reduced use of intensive care
after liver transplantation: patient attributes that determine early transfer
to surgical wards. Liver Transpl 2002; 8: 682–7
10. Buckels JA, Tisone G, Gunson BK, McMaster P. Low haematocrit reduces
hepatic artery thrombosis after liver transplantation. Transplant Proc 1989;
21: 2460–1
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Please see multiple choice questions 1–5.
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