ANESTHETIC MANAGEMENT FOR

LIVER TRANSPLANT

PRESENTER
Dr Neha N M
GUIDE
Dr Amod K S
 OVERVIEW
• Introduction
• Indication and Contraindication
• Preoperative Evaluation
• Intraoperative Management
• Maintenance of Anaesthesia
• Complications
• Post Operative Care
• In 1967,Dr Thomas Starzl performed the first successful transplant
in an 18 month old infant with hepatocellular carcinoma.

• Liver replacement is the sole life saving procedure for patients with
end stage liver disease[ESLD]

• Surgical technique, immunosuppression ,management of

coagulopathy and infections, better recipient selection and
advances in anaesthetic and intensive care management.

• Major goals of liver transplantation are:

- to prolong survival.
- to improve quality of life.
TYPES OF TRANSPLANTATION:
1) Orthotopic transplantation:
– Involves replacing a diseased organ with healthy donor organ
in its normal anatomical position.
– It is the most common type Liver transplant.
– Goal is to replace diseased Liver.

2) Heterotopic transplantation:
– The donor organ is placed in a different location, while leaving
the recipients diseased liver in place.
– Goal is to support or allow recovery of native Liver.
Ideal candidates for liver transplant
• Presence of irreversible disease with life expectancy less
than 12 months.
• Chronic liver disease interfering with patients quality life.
• Liver disease related mortality is greater than transplant
related mortality.
Donor Assessment
• A major limitation to clinical transplantation is the
availability of organ donors.
• Avoidance of damage to the graft during the procedure
are essential in securing optimal function of the
transplant.
• Aggressive donor management protocols to minimize the
adverse physiologic consequences of brain death. These
protocols include respiratory and hemodynamic support,
adequate fluid resuscitation and the initiation of hormone
replacement.
• Brain death is associated with significant instability and minute
to minute management by experienced personnel in the
intensive care unit is necessary to ensure adequate perfusion
of all organs.
• In case of brain dead patients, close monitoring of glycemic
status, input-output maintenance, creatinine levels and dys-
electrolytemia should be corrected.
• Donor’s liver function must be determined. Rapid screening and
serial follow up of liver enzymes and synthetic function are
performed to determine the degree of liver injury and predict the
potential for recovery.
• Routine assessment for diseases that might be transmitted by
the liver graft must include hepatitis screening as well as any
history of the use of toxic substances such as long standing
alcohol consumption.
• Although donor age has been shown to have an adverse impact
on outcome, most programs now consider the use of donors
upto 75-80yrs of age. This approach has been necessary
because of the need for lifesaving organs and is supported by
scientific evidence of a relatively slow aging process occuring
within the liver parenchyma.
• It also appears that grafts from donors with serology positive for
a pathogen present in the recipient can be used with results to
those of transplantation with uninfected grafts as long as the
liver does not have established severe hepatitis or fibrosis.
• Donor and recipient matching are based on ABO blood
group compatibility and size. However these barriers may
be crossed when transplantation is urgent.
• Most surgeons try to match donor-recipient age for
pediatric recipients because variation may have an impact
on long term graft survival.
LIVING DONOR TRANSPLANTATION[LDLT]
• Initial reports about LDLT in the early 20th century
established technical feasibility of the procedure.
• The donor hepatectomy can include left lobes, left lateral
segments or extended right lobe. LDLT has some
advantages for the pediatric recipient and the transplant
population as a whole.
• These include increased graft availability and survival and
decreased morbidity, mortality, rejections and cost.
• Potential donor evaluation should include bedside ABO blood
type compatibility with the recipient(the only need in cadaveric
donor).Also necessary is the exclusion of acute, chronic or viral
illness and liver/biliary system function and anatomy
assessment as well as psychological assessment.
• Although the procedure is relatively safe for the donor over
10% of donors have pre-surgical complications. Surgical
experience and technical modifications have resulted in
significant reduction of these complications.
• The mortality risk of hepatic resection in non-cirrhotic
individuals is extremely low when the operation is performed in
an experienced centre.
SPLIT CADAVERIC-DONOR GRAFT
• LT in small children has been limited by the shortage of
suitable cadaveric donor organs.
• The split is done between the adult recipient(using the
extended right lobe) and the pediatric recipient(using the
left lobe) of the cadaveric donor graft.
• Split cadaveric donor graft was the obvious technical
solution to this problem of pediatric graft availability.
Cold Ischemia time – from the time the organ is
preserved in a hypothermic state until transplant.
• Preservative fluid used for liver storage are:-
– University of Wisconsin solution (gold standard)
– HTK solution (Histidine-tryptophan-ketoglutarate)
– Institut Georges lopez-1 solution (IGL-1)
– Celsior solution.
• Stored at 4degree Celsius.
 INDICATIONS
 End stage liver Disease
Hepatocellular disease:
• Chronic viral hepatitis[hepatitis
Vascular Disease:
C]
• Budd-Chiari Syndrome
• Alcoholic liver disease
• Venocclusive disease
• Cryptogenic cirrhosis
• Chronic drug-induced liver Polycystic Liver Disease
disease
Cholestatic Disease:
• Primary sclerosing cholangitis
• Primary biliary cirrhosis
• Biliary atresia(mostly children)
• Familial cholestatic syndromes
 Hepatic Malignancies not amenable to other therapy
Hepatocellular carcinoma
Cholangiocarcinoma
Carcinoid Tumor
 Fulminant hepatic failure
Drug induced
Acute Viral hepatitis[A,B,C,delta]
Metabolic disease-Wilsons disease, organic acidurias
 Metabolic Diseases affecting Liver
Alpha antitrypsin deficiency
Hemochromatosis
Glycogen storage disease
Urea cycle deficiency
 MELD score 14 or PELD score of 16 or more
 CTP score if 8 or more
 CONTRAINDICATIONS
• Absolute
- Brain death
- Extrahepatic malignancy
- Active uncontrolled infection
-Metastatic hepatobiliary tumors
- AIDS
- Advanced cardiopulmonary disease : critical aortic stenosis, recent drug eluting
stent placement.
- Uncontrolled sepsis
- Inability to comply with medical regimen
- Lack of psychosocial support
- Anatomic abnormalities precluding liver transplant
- Compensated cirrhosis without complications
• Relative
-Obesity[BMI>30]
-Moderate Pulmonary hypertension
-Mild to Moderate aortic stenosis
-Advanced chronic renal failure
-Severe hyponatremia
-Portal veins thrombosis
-Active tobacco use
-Active alcohol abuse
-Active drug abuse
-Advanced Malnutrition
PRE-OPERATIVE EVALUATION:
• Severity of liver dysfunction
• Co-existing morbidity
• Type of Surgery
• Monitoring
• Post operative facilities.
• History: thorough history into risk factors., prior h/o jaundice, alcohol
consumption, use of recreational/ illicit drugs, herbal medications
• Symptoms
• Physical examination:
1) state of hydration
2) Nutritional status
3) Neurological status
4) Assessment of associated complications
Common Investigations are:
1)Full blood count - to establish anaemia, thrombocytopenia or
evidence of infection.
2)Pro-thrombin time-may be raised due to vitamin K deficiency
3)Baseline renal function - in patients with cirrhosis, creatinine in the
normal range may indeed represent renal impairment.
4)Serum Electrolytes, Urea and creatinine
5)ECG and echocardiography - to establish ventricular function and
presence of cardiomyopathy, valvular lesions or raised pulmonary
vascular pressure.
6)CXR - to establish the presence of effusions amenable to per-
operative drainage may be helpful in optimising peri-operative
respiratory function.
7)Pulmonary function test.
8)Abdominal ultrasound - assess liver, presence of ascites
Abdominal magnetic resonance imaging[MRI}-liver anatomy
Upper and Lower GI Endoscopies
Doppler ultrasound to determine patency of portal Vein/hepatic
artery
9)Liver function test.
OT Preparation:

• Warm room to 21-26 degree

• Fluid warming devices
• Airway humidifier
• Forced air warming device
• Rapid fluid infusion system,including pressurised devices
• Availability of blood and blood products
• Blood salvaging devices.
• Standard Monitoring:5 lead ECG,pulse oximetry,Non-invasive blood pressure
and temperature.
• Drugs:Atropine,Epinephrine,Calcium,dextrose,insulin,inotropes,NORAD,
sodium bicarbonate,vasopressors.
INTRAOPERATIVE MANAGEMENT
• Hemodynamic Monitoring:
Central line for CVP monitoring and vasopressor infusions.
Large bore peripheral cannula for rapid blood and fluid infusion.
Invasive arterial blood pressure monitoring.
Introducer sheath can be used for pulmonary artery catheter placement in patients with
pulmonary hypertension.
• CO monitoring: Pulse contour analysis for stroke volume variations.
• Transoesophageal echocardiography(TEE)
• Bispectral Index(BIS)
• Jugular venous oxygen saturation
• Neuromuscular monitoring.
• Diuresis checked hourly to ensure good renal function.
• Monitoring urine output.
PREMEDICATION:
• Since coagulation may be abnormal pre-operatively
intramuscular premedication is not advised.
• Hepatic encephalopathy is another contraindication. If
coagulation and level of consciousness are normal,
standard medications are not contraindicated.
• The dose is usually adjusted downward because of
reduced hepatic function including drug elimination.
Premedication is frequently reduced or even omitted.
• Pre-operative counselling for the patients preparation,
allows family interaction with an alert individual before
surgery.
• However, if a patient desires, short-acting benzo-diazepines
are often appropriate.
INDCUTION
• Rapid sequence induction is performed because many of
these patients have ascites and perhaps the equivalent of
a full stomach.
• Delayed gastric emptying often exists in patients taking
cyclosporine orally.
• Thiopental 4mg/kg,propofol 1-2mg/kg or etomidate 0.3-
0.5mg/kg is used.
• Succinylcholine 1-2mg/kg is added to tracheal intubation
while cricoid pressure is maintained.
• The induction agents are protein bound and the free drug
fraction is increased in liver disease.
• When serum albumin is low ,leading to an enhanced
effect.
• Thiopental and etomidate are metabolized in the liver but
their activity is terminated by redistribution. Hence their
duration of action is normal unless the doses are large or
repeated.
• Propofol is frequently used due to its vasodilator effect.
ANESTHETIC MANAGEMENT
• Fentanyl, sufentanil and alfentanil are suitable opioid analgesic
agents because they have short half-lives and inactive
metabolites.
• Fentanyl does not decrease hepatic oxygen and blood supply or
prevent increase in demand when used in moderate
doses(50mg/kg bolus and 0.5mg/kg/min infusion)
• Halothane is avoided in favour of isoflurane for transplant.
• Halothane, enflurane and isoflurane all reduce liver blood flow but
halothane reduces hepatic arterial flow to a greater extent.
• Nitrous oxide has been used for many years without
increased anesthesia related postoperative hepatic
complications.
• However it is often considered counterproductive because
of its sympathomimetic effect and accumulation in the
intestinal lumen.
• Another reason to avoid nitrous oxide is that potential air
emboli created during the vascular anastomosis.
ABNORMALITIES IN ELECTROLYTES LEVELS
• Hyponatremia
• Hypernatremia
• Hypokalemia
• Hyperkalemia
• Hypomagnesemia
STAGES OF LIVER TRANSPLANT:

• PRE-ANHEPATIC
• ANHEPATIC
• NEOHEPATIC
INTRAOPERATIVE MANAGEMENT PRE-ANHEPATIC STAGE

• This stage begins with surgical incision and ends with the occlusion of flow
through the portal vein ,inferior vena cava and hepatic artery.
• This phase involves dissection and mobilization of the liver.
• With abdominal incision and drainage of ascites, hypovolemia typically
occurs. This should be treated with colloid containing fluid to minimize
preload changes,
• In the presence of pre-existing coagulopathy, fresh frozen plasma is indicated
soon after incision.
• Thromboelastography(TEG) or standard laboratory tests(prothrombin time,
fibrinogen and platelet count) are used to guide the correction of
coagulopathy.
• Maintaining a low CVP can represent an option of reducing
bleeding.
• Adequate volume loading is necessary, cirrhotic patients present
with vasodilation which requires use of vasoactive drugs.
• Correct hypothermia and acidosis.
• Treat Hypocalcaemia.
• Maintain potassium below 4mEq/L
• Treat hyperfibrinolysis and then administer fibrinogen 24mg/kg
and platelets.
• Use of recombinant activated factor 7.
• Veno-venous bypass in case of massive bleeding, hemodynamic
instability, myocardial ischemia, pulmonary hypertension.
INTRAOPERATIVE MANAGEMENT ANHEPATIC STAGE:

• This stage begins with the occlusion of vascular inflow to the liver and
ends with graft reperfusion. Occlusion of the vena cava reduces venous
return by as much as 50%.
• Veno-venous bypass, which diverts inferior vena cava and portal venous
flow to the axillary vein, attenuates the decrease in preload ,improves
renal perfusion pressure ,lessens splanchnic congestion and delays the
development of metabolic acidosis.
• At this stage, anaesthetist should optimise the patient for graft
reperfusion by considering:
Keep serum K level below 4mEq/L
Calcium level should be normalised
Inotropes should be readily available
• Corticoid therapy started intraoperatively with bolus dose
of methylprednisolone aceponate 500mg-1g.
• Some centres prefer using mannitol(0.5g/kg)before IVC
clamping in order to avoid liver blood congestion and
intra-abdominal organ edema.
• Hepatectomy is followed by vascular anastomoses of the
supra and infra hepatic IVC and the portal vein.
• Fibrinolysis may begin during this stage due to an
absence of liver produced plasminogen activator inhibitor
resulting in the unopposed action of tissue plasminogen
activator.
INTRAOPERATIVE MANAGEMENT NEOHEPATIC STAGE:

• The reperfusion of the graft begins the neohepatic stage.

Reperfusion is typically via the portal vein, though the
sequence of revascularization may have implications.
• Reperfusion is associated with abrupt elevations in
potassium and hydrogen ion concentration an increase in
preload and a decrease in systemic vascular resistance
and blood pressure.
• Potentially life threating hyperkalaemia requires calcium
chloride(1-2g) and possibly bicarbonate administration.
However even in the absence of treatment, elevated potassium
levels fall spontaneously within minutes due to redistribution.
• FiO2 should be maintained 100% in order to increase oxygen
stores.
• Cardiovascular stability can be improved by administration of
bolus of 5mg ephedrine five minutes before clamping of IVC, to
maintain MAP of 85-100mmhg.
• If intra-cardiac clots observed 3000-5000IU heparin bolus can
be given.
• Close monitoring of coagulation done via viscoelastic testing.
REPERFUSION SYNDROME
• The exact mechanism is unknown but it may be due to
- High potassium concentrations in the preservative solution
- Donor demographics
- The surgical technique
- Decreased systemic vascular resistance
- Hypothermia
- Metabolic acidosis
- Endogenous vasoactive peptides from the intestine
- Sudden arterial stretching in response to unclamping and
reperfusion
• After initial reperfusion phase the hepatic artery anastomosis is
completed the gallbladder is removed and the bile duct is
reconstructed.
• Hepatic artery reconstruction is mostly done by end-to-end
anastomosis or by a jump graft from the aorta.
• Bile drainage is usually accomplished by choledocho-
choledochostomy and occasionally by Roux-en-Y
choledochojejunostomy.
• Attention should be paid to the diagnosis and management of
significant coagulopathy and resultant bleeding in the
reperfusion phase.
• Laboratory analysis and clinical evidence of surgical bleeding
should be guided to management of coagulopathy.
• When adequate hemostasis is established the abdomen is
closed.
• Hypertension may develop toward end of procedure in some
patients.
PEDIATRIC TRANSPLANTATION

• Biliary atresia is the most common primary diagnosis in

pediatric liver transplant recipients, while metabolic liver
disease represents the second largest group.
• Bleeding may not be severe in these patients because
synthetic function is usually preserved.
• The risk of hepatic artery thrombosis in children lead to
less vigorous correction of any clotting defects. Fresh
frozen plasma is used sparingly and antifibrinolytics are
typically avoided.
IMMUNOSUPPRESSIVE DRUGS
• Cyclosporine is the most commonly used maintenance
immunosuppressive drug.
• Steroid are almost invariably added.
• Azathioprine may be used to reduce dose of cyclosporine altogether
when latter is contraindicated or can no longer be used because of
side effects.
• Anti-lymphocyte globulin preparations including the monoclonal
antibody OKT-3 given for specific indications to prevent rejection,OKT-
3 reacts against all mature T lymphocytes.
• The most prominent is tacrolimus which became an established
immunosuppressant agent for primary and rescue therapy in patients
with liver, kidney and pancreas transplants.
MASSIVE
BLOOD
TRANSFUSIO
N PROTOCOL
POST OPERATIVE CONSIDERATIONS
1.Post operative bleeding
2.Liver Function – Favorable signs regarding hepatic function in the immediate
postoperative period include the following:
– Hemodynamic stability
– Awakening from anaesthesia
– Clearance of lactate
– Resolution of hypoglycaemia
– Normalization of coagulation profile (prothrombin time)
– Resolution of elevated transaminases
– Good renal function
3.Vascular complications
4.Rejection
Graft rejection
• Types of rejection
– Hyper acute (occurs within minutes – 24 hrs after transplant)
– Acute (occurs within 10 days – 3 months)
– Chronic (occurs after 3 months)
• Presents with unexplained episodes of fever, edema,
jaundice, abnormal lab investigations, altered urine
output.
• Rejection can be diagnosed only on the basis of liver
biopsy
POSTOPERATIVE CARE
• Postoperative tracheal intubation is no longer mandatory.
• Fluid shifts or blood loss should not be considered an indication for
postoperative intubation.
• Patient with adequate postoperative liver function and on steroids
tend to be hyperglycemic, which may require insulin infusion.
• Immunosuppression Agents.
• Postoperative pain control is generally achieved with
– Opioids via patient-controlled analgesia
– regional techniques such as TAP block, QL block
– Opioid sparing adjuvants such as ketamine, clonidine.
– Non opioid analgesics such as acetaminophen and carefully monitored
use of NSAIDs.
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