Liver Transplantation

Speaker: Dr S. N Bhagirath

Moderated by Dr Jayanth

History

• First human liver transplantation – 1963

• Attempted by Thomas Starzl

• First recipient was a three year old – unsuccessful

• First Successful transplant was in 1967

Team Work

PERSONNEL INVOLVED

SURGEONS

NEPHROLOGISTS

PAEDIATRICIAN

RADIOLOGIST

PATHOLOGIST

PHYSICIAN

TRANSPLANT CO-ORDINATOR

NURSES

BLOOD BANK PERSONNEL

ANAESTHESIOLOGISTS

SPECIALISTS IN INFECTIOUS DISEASE

HEPATOLOGISTS & INTENSIVISTS

Indications

73%

21%

4%

2%

Decompensated Cirrhosis

Malignancy

Acute Liver FailureMetabolic Disease

Pathophysiology

Chronic Parenchymal Inflammation & Necrosis

Fibrosis

Disruption of hepatic architectureIncreased resistance to blood flow

Portal HTN

Formation of vascular shunts between portal & systemic shunts

10 – 12 mm of Hg of pressure gradient between portal & hepatic veins

Complications

Ascites, Esophageal Varices, Encephalopathy, Hepatorenal Syndrome

Complications - Cardiovascular

Portal HTN

Vasodilators

• Natriuretic Peptides

• VIP• Endotoxin• Glucagon• Nitric Oxide

Circulating volume sequestered into splanchnic circulation

• Low SVR/ Low Arterial Blood Pressure

• Hyperdynamic Circulation – High CO

• Blunted response to Sympathetic stimulation

Cirrhotic Cardiomyopathy

Complications - Cardiovascular

Cirrhotic Cardiomyopathy

• Systolic dysfunction – inability to increase CO

• Diastolic dysfunction – Vulnerability to Heart failure

• Resistance to β-adrenergic stimulation

• Electro physiologic abnormalities

• Autonomic dysfunction

Chronotropic/ Hemodynamic incompetence

Prolonged QTc interval

• Increased risk of CAD

Complications - Pulmonary

Two Entities

Hepatopulmonary Syndrome Porto-Pulmonary Syndrome

• Fluid retention

• Pleural Effusion

• Decreased lung capacity sec to large volume ascites

• α – 1 Antitrypsin deficiency

Broad Etiology

Complications – Pulmonary – Hepatopulmonary Syndrome

Diagnostic Criteria

• Portal HTN• PaO2 < 80 mm of Hg on room air

orAlveolar – Arterial O2 gradient > 15 mm of Hg

• Evidence of Intrapulmonary Vascular Dilatation (IPVD)

More about IPVD • Normally, Micro bubbles/ Albumin injected into venous

circulation get trapped in pulm. capillary bed

• But with IPVD, these are no longer trapped

• They re-appear in left atrium (2D Echo)

• Suggestive of increase in pulm. capillary diameter from

between 8 – 15 μm to 50 – 500 μm

• This compromises O2 diffusion causing hypoxia

Complications – Pulmonary – Porto-pulmonary Syndrome

Definition • Pulm. HTN in presence of Portal HTN

Diagnostic Criteria

• Clinical evidence of Portal HTN• Mean Pulm. artery pressure of 25 mm of Hg. at rest or 30

mm of Hg. during exercise• Mean Pulm. artery occlusion pressure < 15 mm of Hg• PVR > 240 Dyn Sq. Cm2 or 3 Wood units.

Implication • Poor prognosis for liver transplantation (without treatment)

• Post – treatment P.A. pressure < 35 mm of Hg.&PVR < 400 Dyn Sq. Cm2

Favourable candidates for

Liver transplantation

Complications – Renal – Hepatorenal Syndrome

Definition • Pre-renal abnormality due to circulatory derangements

Etiology • NO & other vasodilators which divert circulation thus compromising renal perfusion.

Type I HRS Type II HRS

• Rapidly progressive Renal Failure• Doubling of Creatinine over 2 weeks• Precipitating causes: Sepsis, Peritonitis, Surgical Stress• Median survival – 2 – 4 weeks.

• Median survival – 6 months

Treatment 1. Arginine – Vasopressin2. Nor-Epinephrine, Somatostatin3. Midodrine4. Volume expansion5. TIPS 6. Definitive treatment – Liver Transplantation.

Focus not on renal vasodilation but on

splanchnic vasoconstriction

Complications – Hepatic Encephalopathy

Definition • Serious, reversible neuro-psychiatric complication

Etiology• Hyperammonemia• Gut – derived neurotoxins• γ – Amino butyric Acid• Oxidative stress, Inflammatory mediators• Hyponatremia• Abnormal Serotonin/ Histamine Neurotransmitters

Treatment1. Non-absorbable Disaccharide - Lactulose2. Non-absorbable Antibiotics – Neomycin, Metronidazole,

Rifaximin.3. Floral washout reduces production of Ammonia.

Etiology • Uremia – Sepsis• Glucose & Electrolyte abnormalities• Endocrinopathies• Infections• Vascular lesions

Complications – Ascites

Etiology • Cirrhosis• Malignancy• Cardiac Failure• Renal disease• Pancreatitis• Tuberculosis

Eventuality May progress to Spontaneous Bacterial Peritonitis

Management• Serial Paracentesis• Liver Transplantation• TIPS placement• Peritoneovenous shunt• Never rapidly correct Hyponatremia–Central Pontine Myelinosis

Complications – Varices

Definition • Dilatation of Porto – Systemic shunts sec to Portal HTN

Diagnosis• Wedge Hepatic Venous Pressure (WHVP) > 10 – 12 mm of Hg.• Gold standard – Esophago-gastro duodenoscopy

Acute Variceal Bleeding

1. Intravascular volume resuscitation2. Correction of severe coagulopathy3. Pharmacologic manipulation of portal

pressure (eg. Vasopressin & Somatostatin)

4. Endoscopic variceal ligation5. Elective Intubation6. Balloon Tamponade

Treatment • Non selective β - Blockers (β1 reduces Cardiac Output & β2 causes Splanchnic Vasoconstriction)

• Endoscopic Ligation• TIPS

Buy time until Liver

Transplantation.!

Complications - Hemostasis

• Imbalance between Pro and Anticoagulant factors

• Thrombocytopenia (Splenic sequestration)

• Altered Fibrinolysis (TEG)

• DIC

Why are all these important..?

Liver Transplant Recipient

AUTONOMIC DYSFUNTION HEPATORENAL

SYNDROME

HEPATIC ENCEPHALOPATHY

ASCITES

VARICES

ACUTE VARICEAL BLEEDING

COGULATION ABNORMALITIES

PRE-EXISTENT CO-MORBIDITY

HEPATOPULMONARY SYNDROME

PORTOPULMONARY HYPERTENSION

BUNTED RESPONSE TO SYMPATHETIC STIMULATION

CIRRHOTIC CARDIOMYOPATHY

For Pre-operative preparation

Alert the Blood Bank

Neurologist consultation

Nephrologist consultationCardiologist

consultation, Inotropic

Support, etc.

Pulmonologist consultation

Oral immunosuppresants

/ bowel decontamination

antibiotics

Preoperative considerations

1. Complete Blood Work Up

• Hb, Platelets, WBCs, INR, Coagulation profile with Fibrinogen and PTT, ABG

• Electrolytes – Na+, K+, Cl-, Mg2+ Ca2+, Phosphate

2. Liver Function Tests

• Albumin (drug binding and oncotic pressure)

3. Renal Function Tests

• Urea and Creatinine

5. Baseline Cytomegalovirus and Epstein Barr Virus status.

6. Blood cultures

7. Chest X Ray

• Fluid overload, Infection

5. 2D Echo (Pulm. HTN/ Hepatopulmonary Syndrome)

6. Complexity of previous surgery (e.g.: Kasai’s Procedures)

Preoperative considerations

1. Specific Medication

• Immunosuppressants: Tacrolimus 0.2 mg/kg, Cyclosporine 5 mg/kg

• Mycostatin: 2 – 5 ml

• Depending on Coagulation status: transfuse 1 FFP.

2. Premedication

• Anxiolysis (especially in children): 0.25 – 0.5 mg/kg

• Supplemental O2 (in presence of HPS)

3. Counseling

• Psychological counseling to dispel fears and answer any lingering doubts.

Intraoperative considerations - Preliminaries

1. Rapid Sequence Induction

2. Arterial Blood Pressure monitoring

3. CVP

4. PA Cath (?)

5. TEE

6. Rapid Infusion Systems

7. Volatile Anaesthetic – 0.5 to 1.0 MAC (preferably Isoflurane as it

preserves Splanchnic Circulation)

8. Opioid (Fentanyl)

9. Muscle Relaxant (Cis-atracurium)

Intraoperative considerations – Stages of surgery

1. Preanhepatic stage

Surgical Incision Vascular exclusion of native liver

2. Anhepatic stage

Vascular occlusion Graft Reperfusion

(inflow to liver obstructed)

3. Neohepatic stage

Post reperfusion via portal vein

Preanhepatic stage (Dissection)

Subcostal Incision dissection of liver retaining the vascularity.

1. Trial clamping of infrahepatic IVC for 30 – 60 seconds

2. Anesthesiologist should judge CVS effects, adequacy of blood replacement and

patients ability to withstand drop in preload.

3. If SBP falls by 70% of pre-existent values, then bypass support may be needed.

Trial Clamping

Preanhepatic stage (Dissection Phase) Considerations

1. Blood loss, Manipulation of liver hilum and direct compression of IVC.

2. Adequate volume resuscitation (blood & colloid) is required.

3. Calcium chloride is preferred over Calcium Gluconate.

Anhepatic stage

Clamping of

• Suprahepatic IVC

• Infrahepatic IVC

• Portal Vein

• Hepatic Artery

Diversion of portal

flow via Venovenous

bypass to axillary v.

Clamping of vessels before hepatectomy.

Anhepatic stage

Order of anastomosis

• IVC Clamp – Suprahepatic,

then Infrahepatic IVC

• Portal Vein

• Hepatic Artery

Order of clamping

1. Suprahepatic IVC

2. Infrahepatic IVC

3. Portal Vein

4. Infrahepatic IVC

Removal of Vascular clamps

• Portal Vein

• Suprahepatic IVC

• Infrahepatic IVC

Anhepatic stage

DisadvantagesAdvantages

Venovenous bypass

1. Prevention of precipitous

reduction in preload

2. Improves Renal Perfusion

Pressure

3. Lessens Splanchnic

Congestion

4. Delays development of

Metabolic Acidosis

1. Air Embolism

2. Thromboembolism

3. Inadvertent decannulation

4. Delays development of

Metabolic Acidosis

Fibrinolysis during anhepatic stage is a risk due to unopposed action of tissue

plasminogen activator.

Neohepatic stage

1. When was it harvested i.e. Graft Ischemia time.?

2. Is the Graft compatible.?

3. Is the donor an adult or child.? (dictates requirement of size down surgery on

the side and consequent blood loss)

4. Has the new liver been washed to minimize reperfusion effects.? (washed

with Stabilized Human Serum, Ringers Lactate or Albumin)

5. If the Liver was cut down, how was the free edge sealed (This has an impact

on blood loss following revascularisation)

What do we need to know about the new liver..?

Neohepatic stage

Reperfusion of graft through portal vein

Consequences of Reperfusion

1. Hyperkalemia

• ECG changes

• Calcium Chloride/ Sodium Bicarbonate – treatment

• Albuterol & Insulin

• Intraoperative Dialysis

2. Hydrogen ion concentration increases

3. Increase in preload

4. Decrease in SVR, decrease in B.P.

Post – Reperfusion Syndrome

Azathioprine,Medrol 10 mg/kg

Antibiotics

Neohepatic stage

Systemic Hypotension + Pulmonary HTN (5 mins)

1. Probable Causes

• Hyperkalemia

• Acidosis

• Hypothermia

• Air/ Thrombotic emboli

• Vasoactive substances

• First venous reperfusion, then arterial anastomosis and biliary reconstruction comes later.

Post – Reperfusion Syndrome

1. Risk factors for PRS

• Elevated Preanhepatic K+ levels

• Use of “donated after cardiac death” liver

• Suboptimal grafts i.e.

> 50 yrs. of age h/o Cardiac arrest Hypotension Need for high dose inotropes > 5 days of ICU stay Elevated Liver fat content

• Graft Cold Ischemia time > 6 hours

Steps & Implications

HypovolemiaColloid

Infusion

Bleeding/ Coagulopathy

1. FFP after Incision

2. Prothrombin Complex Concentrates (PCCs)

3. Recombinant activated factor VII

4. Parameters to assess

• TEG

• PT

• Fibrinogen

• Platelet Count

Risk of TRALI, Circ. Overload

Thrombo-embolic complications

I. Abdominal Incision & Drainage of Ascites

II. Hyponatremia Central Pontine Myelinosis

Steps & Implications

Hyperkalemia

III. Blood Transfusions - Citrate Intoxication

VII. Other precautions

Hypocalcaemia, Hypomagnesaemia

IV. Reperfusion

1. Hourly blood gases

2. Electrolytes, Glucose, Ionised Ca2+ and Hb levels

3. Maintain Urine Output

V. Hyperglycaemia Wound site infection

Diuretics, Insulin + Glucose or last resort Dialysis

VI. Massive Infusions Hypothermia Heated Venovenous bypass

1. Preanhepatic stage

2. Anhepatic stage

3. Neohepatic stage

Bleeding

Cardiovascular Compromise

Hypoglycemia

Hypoglycaemia

Hypocalcemia

Severe Hypotension

Bradycardia

Arrhythmia

Dyselectrolytemia

Signs of successful graft function

1. Decreased Ca2+ requirements.

2. Improvements in acidosis.

3. Increased Urine Output.

4. Rise in core temperature.

5. Bile Output.

Antifibrinolytics

Graft Endothelial cell

Tissue Plasminogen activator

releases

Severe Fibrinolysis Treatment with Antifibrinolytics & cryoprecipitates.

Post Operative Care

Broad Based goals

1. Hemodynamic Stability

2. Metabolic Homeostasis

3. Analgesia• Opioids• Patient Controlled infusion • Epidural analgesia is contraindicated (Coagulopathy)

4. Monitoring Graft Function• Transaminase levels• PT• Bilirubin levels• Bile• Urine Output• Acid Base Status

Post Operative Care

Broad Based goals

5. Watch out for

• Bleeding

• Bile leaks

• Vascular thrombosis

• Primary Non-function

• Hyperglycemia (steroid usage)

6. Bear in mind

• Derangement of Transaminase levels (first 2 -3 days) is common.

Persistence beyond this period should raise suspicion of Hepatic

Artery Thrombosis.

• No clear guidelines for early extubation.

Organ Matching and allocation

Primary Criteria

1. ABO Blood type

2. Graft Size

• ABO incompatible is for emergent situations.

• Disease severity decides que priority

• Disease severity was earlier assessed by Child – Turcott – Pugh Score

1 2 3

Encephalopathy None 1-2 3-4

Ascites Absent Slight Moderate

Prothrombin time <4 4-6 >6

Albumin >3.5 2.8 – 3.5 <2.8

Bilirubin <2 2-3 >3

Organ Matching and allocation

• Presently Disease severity is assessed by MELD score

1. Serum Bilirubin

2. Creatinine level

3. INR

• MELD score fails to recognise HCC patients early on so they are given priority.

• MELD score between 12 – 14 benefit most from Liver Transplantation.

Living Liver Donor

1. First introduced in 1988

2. Full regeneration in 2 – 3 weeks

3. For pediatric recipients – left lobe is preferred

4. For adult recipients – right lobe is preferred

Anaesthetic Management

1. G.A.+ IPPV + Muscle relaxant

2. Adequate Venous Access

3. Arterial line

4. Nasogastric Tube

Living Liver Donor

1. During mobilization of liver watch for hypotension and bradycardia

2. To minimize blood loss

• Maintain low CVP (<5 cms H2O) (decreases Graft Edema)

• However, newer surgical techniques no longer require low CVP.

Anaesthetic Management

Blood Saving Strategies

1. Cell salvage technique

2. Preop donation of 1 – 2 units of autologous blood.

3. Intraoperative isovolemic hemodilution with retrieval of 1 – 2 units of

blood.

Living Liver Donor

1. Living donors can be extubated

2. Discontinuation of Mechanical ventilation reduces intrathoracic

pressure which reduces congestion.

3. Maintain optimal perfusion of liver by

• Adequate CO

• Avoidance of Hypovolemia

• Anemia

• Hypothermia induced coagulopathy

4. Post op analgesia

• Epidural Placement is advised (risk of hematoma due to coagulopathy have to be weighed)

5. Statistical

• R Hepatectomy has higher complication than L Hepatectomy.

Gracias