Liver transplantation is a complex procedure that requires careful anaesthetic management due to the pathophysiological changes associated with end-stage liver disease. Key considerations include monitoring for haemodynamic instability, coagulopathy and metabolic disturbances. Frequent intraoperative monitoring and correction of abnormalities are important to assess graft function and optimize patient outcomes.

1. ANAESTHESIA FOR LIVER
TRANSPLANT
Dr.Sandeep
Narayana medical college
Nellore.

2. OVERVIEW
• INTRODUCTION
• INDICATIONS AND CONTRAINDICATIONS
• SCORING SYSTEMS
• PATHOPHYSIOLOGY OF END-STAGE LIVER DISEASE
• PREOPERATIVE EVALUATION AND COMPLICATIONS
• INTRAOPERATIVE MANAGEMENT
• MAINTENANCE OF ANAESTHESIA
• PRE-ANHEPATIC PHASE
• ANHEPATIC PHASE
• POST ANHEPATIC PHASE
• HAEMOSTATIC DISORDERS AND MANAGEMENT
• POSTOPERATIVE CARE

3. INTRODUCTION
• Liver transplant surgery is a fairly uncommon procedure in our
country.
• Liver replacement is the sole life saving procedure for patients
with end stage liver disease(ESLD).
• The most commonly used technique is orthotopic
transplantation

4. • The two major goals of liver transplantation are
– to prolong survival and
– to improve quality of life.
• Improvements in organ preservation, surgical technique, the
advent of better immunosuppressive agents, the management of
coagulopathy, and the Rx of infections, has resulted in a great
expansion of this procedure

5. INDICATIONS
Acute liver failure
• Acute hepatitis A
• Acute hepatitis B
• Drug/toxin hepatotoxicity
Cirrhosis from chronic liver diseases
• Chronic hepatitis B virus and chronic
hepatitis C virus infection
• Alcoholic liver disease
• Autoimmune hepatitis
• Cryptogenic liver disease
• Primary biliary cirrhosis and primary
sclerosing cholangitis
• Secondary biliary cirrhosis
Metabolic Disorders
• Alpha-1 antitrypsin deficiency
• Hereditary hemochromatosis
• Wilson’s disease
• Glycogen-storage disorders
• Type 1 hyperoxaluria
• Familial homozygous
hypercholesterolemia
Malignancy
• Primary hepatic cancer:
hepatocellular carcinoma and
cholangiocarcinoma
• Metastatic: carcinoid tumors and islet
cell tumors
Miscellaneous
• Polycystic liver disease
• Budd-Chiari syndrome

6. CONTRAINDICATIONS
Absolute contraindications
• Brain death
• Extrahepatic malignancy
• Active uncontrolled infection
• Active alcoholism and substance abuse
• AIDS
• Severe cardiopulmonary disease-CAD, PULM. HTN,
• Uncontrolled sepsis
• Inability to comply with medical regimen
• Lack of psychosocial support
• Anatomic abnormalities precluding liver transplantation
• Compensated cirrhosis without complications
Relative contraindications
• Cholangiocarcinoma
• Portal vein thrombosis
• Psychologic instability

7. TESTS TO EXCLUDE
CONTRAINDICATIONS
• INFECTIOUS DISORDERS : HIV, Syphilis, EBV, CMV, Toxoplasmosis
• MALIGNANCY :
– Colonoscopy / ERCP in primary sclerosing cholangitis
– In HCC: bone scan, lung CT (metastatic work-up) Screening (colon,
breast, cervical, prostate cancer)
• CARDIOPULMONARY STATUS : CXR, ECG,2D-ECHO, Thallium
stress test, coronary angiography, PFT

8. SCORING SYSTEMS
• Child-Turcotte-Pugh (CTP) classification

9. DRAWBACKS:-
• Ascites and encephalopathy, are subjective because they are
assessed by physical examination alone.
• Second, when other methods are used (ultrasonography,
psychometric testing, EEG), a different degree of severity is
diagnosed
• The absence of an assessment of renal function, which is a
well-established prognostic marker in cirrhosis

10. MODEL FOR END-STAGE LIVER DISEASE (MELD)
SCORE:-
It is a mathematical formula based on the following factors:
1. Creatinine (for adult patients undergoing dialysis twice a
week within the last week, the creatinine value would be
automatically set to 4 mg/dL)
2. Bilirubin (mg/dL)
3. International normalized ratio

11. • Predictive of 3-month mortality in patients
with chronic liver disease.

12. • Pediatric End-Stage Liver Disease (PELD)
scoring system incorporates the following criteria :
– Albumin
– Total bilirubin
– INR
– Growth failure
– Age (<1 y)
• PELD score = 0.436 (age [<1 y]) – 0.687 x Log e
(albumin g/dL) + 0.480 x Log e (total bilirubin mg/dL)
+ 1.857 x Log e (INR) + 0.667 (growth failure [<-2 SD
present])

13. PATHOPHYSIOLOGY
CNS CHANGES:
• Hepatic encephalopathy and Raised ICP are common
• Accumulation of NH3 and Mn leads to alteration in NT like GABA,
Glutamate and NO.
• The enzymes of the urea cycle are absent in the brain.
• The resulting accumulation of glutamine, an osmotic compound,
targets the glial astrocytes and results in cerebral edema in acute liver
failure
• Recently, the blood breakdown products hemin and protoporphyrin IX
have been suggested as possible endogenous BDZ contributing to
hepatic encephalopathy because they are potent activators of GABA
receptors

14. CARDIOVASCULAR SYSTEM
• Hyperdynamic state characterized by increased cardiac output
and arteriolar vasodilatation
• Vasoactive substances bypassing normal hepatic metabolism
are most likely responsible.
• Cannabinoids, Nitric oxide and guanosine 3,5-cyclic
monophosphate (cGMP) have been implicated as mediators
• Cardiomyopathy has been associated with alcoholic cirrhosis
and hemochromatosis

15. • Rhythm disturbances may result from electrolyte or acid–base
abnormalities.
• Evaluate for IHD-
– Dobutamine stress echo (DSE) is the preferred preoperative
screening study because it assesses the adequacy of
myocardial oxygen supply, valvular function, and the
presence of intrapulmonary shunting or portopulmonary
hypertension

16. PULMONARY SYSTEM
• Restrictive lung disease
• Intrapulmonary shunts
• Pulmonary hypertension

17. PULMONARY SYSTEM
HEPATOPULMONARY SYNDROME
Decreased oxygenation (PaO2 <70 mm Hg or a PAO2 - PaO2
gradient >20 mm Hg on room air) associated with
intrapulmonary vascular dilation.
• A hallmark of this syndrome is intrapulmonary shunting.
• Presence of orthodeoxia is a significant clue
• Resolves spontaneously after liver transplant

18. PULMONARY SYNDROME
PORTOPULMONARY HYPERTENSION:
(1) Mean pulmonary arterial pressure greater than 25 mm Hg,
(2) Pulmonary vascular resistance greater than 120 dyne · sec ·
cm-5, and
(3) Pulmonary capillary wedge pressure less than 15 mm Hg in
the setting of portal hypertension

19. RENAL SYSTEM
• Renal dysfunction is usually the result of
– Primary renal disease
– Acute tubular necrosis
– Hepatorenal syndrome(HRS).
• For diagnosis of HRS
– A urinary sodium level <10 mEq/L or a fractional excretion
of sodium <1% ,
– Creatinine level of more than 1.5 mg/dl,
– A urine volume of less than 500 mL/day

20. • Spontaneous bacterial peritonitis is considered the most
frequent cause of renal failure in patients with cirrhosis
• The mechanism of hepatorenal syndrome is thought to be a
combination of reversible renal vasoconstriction in
structurally normal kidneys and changes in vasoconstrictor
and vasodilator factors.

21. • There are two types of hepatorenal syndrome.
• Type I :
– Rapid onset over weeks, progressive and has high
mortality.
– Renal function may recover spontaneously when liver
function improves
– Most common in patients with acute liver failure, alcoholic
hepatitis, or acute decompensation of CLD
• Type II
– Less acute
– Seen in patients who become resistant to diuretic therapy.

22. HEMATOLOGICAL
– Hypocoagulability and Impaired synthesis of coagulation
factors (except factor VIII, Von Willebrand Factor)
– Hypofibrinogenaemia occurs in the terminal stages of liver
failure
– Impaired synthesis of coagulation inhibitors
– Synthesis of abnormal clotting proteins
(dysfibrinogenaemia)
– Insufficient clearance of activated and degraded clotting
products
– Vitamin K deficiency

23. • Enhanced fibrinolytic activity
– Increased levels of circulating t-PA activity(impaired
hepatic clearance, secondary to coagulation activation,
induced by portal hypertension)
– Diminished synthesis of fibrinolysis inhibitors(alpha 2
antiplasmin, PAI-1)
• Quantitative and qualitative platelet defects
– Increased splenic pooling
– Accelerated immune mediated platelet destruction
– Thrombin dependent platelet consumption
– Defective bone marrow destruction
– Disturbed platelet vessel wall interaction

24. Gastrointestinal System
• Portal pressure increases
• Once a critical level of portal hypertension is reached, portosystemic
collaterals form to decompress the portal system.
• Problems related to Portal Hypertension
a) Oesophageal Varices
b) Hypersplenism
c) Ascites
d) Spontaneous Bacterial Peritonitis (SBP)

25. Hepatic Synthetic Function
• Plasma concentrations of
– albumin,
– plasma cholinesterase and
– coagulation proteins
are decreased in patients with liver disease

26. Metabolic dysfunction
• Glucose metabolism :-
– Diminished hepatic glycogen stores as well as impaired
gluconeogenesis in patients with liver disease may result in
severe hypoglycaemia.
– Hence high dose IV glucose infusions must be continued
during patient transport as well as intraoperatively, and
blood glucose concentrations should be measured
frequently during surgery.

27. • Ammonia –
– It is produced by deamination of amino acids and other
organic amines and is converted to urea by the liver.
– The BUN level may therefore be low in patients with ESLD,
whereas the ammonia concentration may be markedly
elevated.
– Ammonia itself is neurotoxic and its accumulation in the
blood is associated with hepatic encephalopathy

28. PHARMACOLOGY

29. Surgical procedure
• Dissection phase
• Anhepatic phase
• Reperfusion (neohepatic) phase

30. PREOPERATIVE CONSIDERATIONS
• Most tests are likely to show that either the patient is fit for
surgery without any further medical therapy, or medical
management is needed before liver transplantation.
• Screening for any new infections on the day of surgery also is
crucial because new-onset or uncontrolled ongoing infections
may require postponement of surgery.
• Avoid intramuscular injectons

31. Common investigations are
• Full blood count – to establish anaemia,
thrombocytopenia or evidence of infection.
• Pro-thrombin time –PT may also be raised due to
vitamin K deficiency;
• Baseline renal function – in patients with cirrhosis a
creatinine in the normal range may indeed represent renal
impairment.
• S.Electrolytes

32. • ECG and echocardiography - to help establish ventricular
function and the presence of cardiomyopathy, valvular lesions or
raised pulmonary vascular pressure.
• Exercise ECG or stress echo – the chronic state of
vasodilatation may mask ischaemia by limiting ventricular workload,
stress testing may be useful where undiagnosed ischaemia is
suspected.
• CXR or ultrasound imaging of chest - to establish the
presence of effusions amenable to preoperative drainage, may be
helpful in optimising peri-operative respiratory function.
• Pulmonary function tests -

33. BLOOD PRODUCTS
• 10 U Of Red Blood Cells
• 10 U Of Fresh Frozen Plasma
• 4 U Of Single-donor Platelets
• 10 U Of Cryoprecipitate

34. • Prepare the theater

35. INTRAOPERATIVE MANAGEMENT
• Hemodynamic monitoring
• Adequate fluid flow sheets should be maintained.
• The frequency of blood sampling for laboratory analysis is
dictated by the medical condition of the patient, progress of
the procedure, and experience of the transplant team

36. LidCo
Monitor

37. • i.v access
• No epidural- deranged coagulopathy
• Pulmonary artery catheter, TEE, IBP and CVP monitoring, after
induction

38. Induction
• The patient should only be transported to the operating
theatre once the donor organ has been harvested and deemed
suitable for transplantation.
• Premedication
• Induction- Propofol, Thiopentone, Etomidate with or without
opioid and short or intermediate acting NMBD

39. Issues
• An increased risk of pulmonary aspiration.
• Nasotracheal intubation is contraindicated
• Appropriate tracheal tube size and positioning are especially
important in infants and children undergoing LT.
• Alterations in hepatic drug metabolising capacity in patients
with liver disease will influence the rate of elimination but not
the duration of action after a single IV injection.

40. • ESLD results in
– changes in hepatic blood flow,
– decreased ability to biotransform certain drugs,
– hypoalbuminemia, and
– altered volume of distribution.
• Sufentanil and Propofol have extrahepatic metabolism.
• Cisatracurium or atracurium

41. • A rapid-sequence induction is often warranted
• Postinduction hypotension may occur as a result of the very
low systemic vascular resistance and relative hypovolemia of
these patients.
• Avoid Halothane.

42. • After induction get advanced venous access
• Correction of severe coagulopathy before line placement may
be considered
• Intraarterial line, central venous cannulation, pulmonary
artery catheter, large bore i.v cannulas
• Cardiac output monitoring

43. Advanced Venous Access

45. Ventilatory monitoring:-
• Inspired/ expired gas oxygen
• Vapour monitoring- Isoflurane/ Sevoflurane
• Airway pressure
• End tidal CO2- changes in pulmonary blood flow ( cardiac
output) to detect air embolism
• Minute ventilation

46. ICP MONITORING
• It is indicated in patients with severe encephalopathy and is
initiated in the ICU to determine the need for and assess
response to therapies like hyperventilation, osmotic diuresis
and barbiturate administration.
• Persistence of increased ICP and reduced CPP despite such
therapies may preclude LT, particularly because ICP has been
shown to increase following reperfusion of the liver graft.

47. • An orogastric/nasogastric tube is placed to decompress the
stomach and improve surgical exposure.
• Before the incision is made, appropriate antibiotic and
immunosuppressive (e.g., steroid administration) coverage
should be ensured.
• Maintain normothermia (prolonged exposure, major fluid shifts,
and the implantation of a cold organ)

48. Blood sampling:-
TEG, ABG analysis including electrolytes, blood glucose, haemoglobin
– Baseline
– Hourly in pre anhepatic phase
– 15 minutes before anhepatic
– 1 hour into anhepatic
– 5 minutes before reperfusion
– 15 minutes after reperfusion
– Hourly after reperfusion in OT
– Post operatively in Liver ICU
ENSURE TO PREVENT HEPARIN CONTAMINATION FOR TEG

49. Maintainence
• A balanced technique using volatile anesthetics in an
oxygen/air mixture and opioids results in stable intraoperative
hemodynamics.
• A combination of opioids and BDZ and TIVA with propofol also
have been used for liver transplantation.
• N2Oshould not be used to avoid intestinal distention, and
because in selected cases (not always predictable) a Roux-en-
Y choledochojejunostomy is done at the end of the
procedure.

50. • Significant coagulopathy, blood loss, and electrolyte and
metabolic derangements require frequent intraoperative
laboratory tests.
• Measurement of ABG, blood glucose, electrolytes (sodium,
potassium, and ionized calcium), and Hct is routine in most
transplant centers.
• Monitoring of ABG allows one to assess oxygenation and base
deficits and possibly lactate levels.
• Correction of the base deficit and reduction in lactate levels
may be indirect indicators that the donor liver is functioning
adequately.

51. • Glucose metabolism may worsen during liver transplantation,
and progressive hyperglycemia may ensue, especially in the
reperfusion phase.
• Several mechanisms have been implicated, including
enhanced glycogenolysis by the donor liver, decreased
glucose use, and insulin resistance

52. • The PT,INR, PTT, fibrinogen, and platelets are measured
by
– Thromboelastography
– Activated clotting time
• Severe coagulopathy and intraoperative blood
loss remain the most significant problems

53. • The administration of FFPs, RBCs, platelets, and
cryoprecipitate remains the mainstay of therapy for blood loss
and coagulopathy during liver transplantation.
• Aprotinin, aminocaproic acid, tranexamic acid, and conjugated
estrogen
• Recombinant factor VIIa

54. Dissection phase
• The surgical goals of the dissection phase are to mobilize the
vascular structures around the liver
• Manipulation of the liver and sudden decompression of the
abdomen can cause hypotension
• Adequate fluid replacement is essential

55. • Diuresis should be maintained with mannitol / dopamine/
fenoldopa/loop diuretics
• During the end of the dissection stage, the donor organ,
which is stored in preservation solution, is flushed with
crystalloid or colloid solution on a separate table

56. Anhepatic phase
• During the anhepatic stage, the new liver is primarily
implanted by either Infracaval Interposition Or
Piggyback Technique.
• The choice of surgical technique has important anesthetic
implications.

57. INFRACAVAL INTERPOSITION
• Complete vascular occlusion is established by clamping the
hepatic artery, portal vein, infrahepatic vena cava, and
suprahepatic vena cava

58. • Because the IVC is occluded, cardiac preload becomes
dependent on collateral flow
• Cardiac output often decreases significantly with an
accompanying increased heart rate.
• If VVBP is not used, volume loading with a target CVP of 10 to
20 mm Hg and occasionally small infusions of vasopressors
(e.g., phenylephrine) are needed before the infrahepatic and
suprahepatic caval clamps are placed to prepare for the
anhepatic phase.

59. • As the response to caval occlusion may differ among patients,
a temporary “test clamp” on the IVC may guide management
before vascular clamps are permanently placed.
• Alternatively, VVBP can be instituted before vascular exclusion
of the liver is established.
• Bypass is usually accomplished by cannulation of the femoral
and portal veins with diversion to the suprahepatic vena cava
through the axillary, subclavian, or jugular vein

60. • Advantages of VVBP include
– improved hemodynamic stability,
– improved perfusion of organs during the anhepatic phase,
– decreased red blood cell and fluid requirements,
– splanchnic decompression,
– reduced renal impairment,
– limited metabolic impairment, and
– a reduced incidence of pulmonary edema
• Lymphocele, hematoma, major vascular injury, nerve injury,
pulmonary air embolism, and death have been associated
with VVBP

61. PIGGYBACK TECHNIQUE
• The vena cava is partially occluded during the anhepatic
phase.
• Although improved hemodynamics has been shown, it is
considered surgically more difficult than caval interposition,
and may lead to greater technical complications.

62. • The anhepatic stage begins with excision of the native liver
and control of bleeding.
• The ice-cold liver donor graft is placed into the surgical field.
• The suprahepatic, infrahepatic, and portal vein anastomoses
are completed in that order.
• The hepatic artery anastomosis can be performed before
reperfusion or after restoration of blood flow .
• Profound acidosis and hypocalcemia frequently develop
during the anhepatic stage, so laboratory parameters should
be monitored closely.

63. • Fluid management can be challenging, and the return of
significant volume when the clamps are released at completion
of the vascular anastomoses must be anticipated.
• Aggressive fluid management to maintain adequate B.P, may
result in fluid overload with possible cardiopulmonary
compromise and considerable liver and intestinal swelling.
• An engorged liver and intestines may pose a significant technical
challenge for the surgeon during the reperfusion phase,
especially when performing a Roux-en-Y
choledochojejunostomy.

64. • At the end of the anhepatic phase, the vascular clamps are
removed in staged fashion, and each anastomosis is inspected
for leakage.
• The return of preload by establishment of continuous caval flow
results in normal or supranormal filling pressure.
• Removal of the portal vein clamp allows blood flow from the
splanchnic circulation into the donor liver and constitutes the
BEGINNING OF THE REPERFUSION PHASE.
• The most critical part of the reperfusion phase is the period
immediately after the vascular clamps are removed from the
liver graft.
• Significant hemodynamic instability and cardiac arrest can occur
within seconds to minutes of unclamping, particularly after
unclamping the portal vein.

65. • Reduced cardiac contractility, arrhythmias, severe
bradycardia, profound hypotension, and hyperkalemic arrest
all have been reported, and anesthetic management is
directed at maintaining or recovering cardiovascular stability.
• This goal may require immediate pharmacologic intervention,
such as the administration of epinephrine, atropine, calcium,
or occasionally sodium bicarbonate.
• Methylene blue has been shown in one small study to
attenuate hemodynamic changes of the reperfusion
syndrome.
• Preoperative placement of external pads may be helpful for
immediate postreperfusion cardiac arrest.

66. Reperfusion syndrome
• The exact mechanism is unknown and remains elusive.
– High potassium concentrations in the preservative solution (UW
solution),
– Donor demographics,
– The surgical technique, and
– Decreased systemic vascular resistance.
– Hypothermia,
– Metabolic acidosis,
– Endogenous vasoactive peptides from the intestine, and
– Sudden atrial stretching in response to unclamping and reperfusion.

68. • After the 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.

69. • Laboratory analysis and clinical evidence of surgical bleeding
should guide management of the coagulopathy.
• When adequate hemostasis is established, the abdomen is
closed.
• Hypertension may develop toward the end of the procedure
in some patients, and treatment should be initiated before
leaving the operating room.

70. Hemostatic management
Dissection phase:-
• Intrinsic haemostatic deficiencies can be worsened by
iatrogenic haemodilution.
• During this stage patients may exhibit enhanced fibrinolytic
activity as monitored by TEG.

71. ANHEPATIC PHASE
• Hyperfibrinolysis is the most striking abnormality and it occurs
late during the anhepatic phase and worsens with
revascularisation of the new liver.
• Frank fibrinolysis with evidence of diffuse bleeding may occur
in up to 20% of patients.
• Fibrinolysis is caused by abrupt increases in tissue
plasminogen activator from graft endothelial cell release and
the lack of hepatic clearance during the anhepatic period.

72. Treatment
• RBCs are transfused to maintain a Hct around 30%.
• FFP is given to maintain the PT below 1.2-1.5 times normal.
• Platelets are kept above 50X109 L-1.
• TEG based coagulation therapy has also been proposed where
administration of a fluid mixture of packed cells, FFP`s, and
crystalloids in a ratio of 3:2:2.5 for volume replacement.
• The infusion of platelets for maximum amplitude less than
40mm; cryoprecipitate for poor clot formation rate and
additional FFP for prolonged reaction time(>12min).
• Those in favour of this TEG based therapy argue that blood
requirements decreased significantly compared to controls.

73. Postoperative considerations
1.Post operative bleeding
2.Liver Function
– Favourable signs regarding hepatic function in the immediate
postoperative period include the following:
1. Hemodynamic stability
2. Awakening from anaesthesia
3. Clearance of lactate
4. Resolution of hypoglycaemia
5. Normalization of coagulation profile (prothrombin time)
6. Resolution of elevated transaminases
7. Good renal function
3.Vascular complications
4.Rejection

74. Postoperative care
• Postoperative tracheal intubation is no longer mandatory
• Fluid shifts or blood loss perse should not be considered an
indication for postoperative intubation
• Analgesic requirements in patients with ESLD undergoing liver
transplantation appear to be significantly decreased
compared with other major abdominal surgery

75. • Frequent assessment of cardiac and pulmonary function,
serum glucose and electrolytes, RFT, LFT, and coagulation and
the blood count is crucial.
• Patients who have adequate postoperative liver function and
have received steroids tend to be hyperglycemic, which may
warrant an infusion of insulin.
• Immunosuppression

76. THANK YOU