Liver Transplantation

OVERVIEW

Liver transplantation is almost a routine procedure in ICU now, with >90% 1-year survival

  • Orthotopic liver transplantation (OLT) involves recipient hepatectomy, revascularisation of the donor graft and biliary reconstruction
  • 1 in 5 have rejection in first year, most occur early post-op (85% in first month)

TYPES OF LIVER TRANSPLANTATION

Techniques

  • vena cava preservation (piggy back technique)
  • portal bypass (internal temporary porto-venal shunt or external veno-venous bypass)

These usually involve end-to-end anastomosis of:

  • hepatic artery
  • portal venous anastomosis
  • biliary duct (if not possible then choledochojejunostomy may be needed; T-tube for external drainage is rarely performed now)

Gall bladder is routinely removed

Graft types

  • full graft
  • reduced size graft
  • right or left split graft (one liver split between two recipients; higher risk of bile leaks, bleeding, collections)
  • auxillary graft (subtotal recipient hepatectomy + reduced size graft; for metabolic disorders or acute hepatic failure where liver may regenerate; auxillary liver degenerates following withdrawal of immunosuppression)

Type of donation

  • after brain death
  • non-beating heart donor (warm ischemia time must be <30 min)
  • living donor transplantation

DISEASE LEADING TO POSSIBLE TRANSPLANTATION

Acute

  • fulminant hepatic failure (paracetamol and non-paracetamol)
  • trauma
  • post-operative

Chronic

  • alcoholic liver disease (must be abstinent for > 6 months)
  • chronic hepatitis (Hep B and C, autoimmune)
  • primary biliary cirrhosis
  • primary sclerosing cholangitis
  • hepatocellular carcinoma
  • liver metastasis (primary tumour fully resected)

Children

  • biliary atresia
  • metabolic diseases causing cirrhosis (Wilson, alpha 1 anti-trypsin deficiency)
  • primary hepatic tumours
  • fulminant hepatitis

CRITERIA FOR TRANSPLANTATION IN CHRONIC LIVER DISEASE (MELD/PELD Scores)

Child Pugh B and C

  • bilirubin >3-5mg/dL
  • albumin < 28
  • INR > 1.7
  • hepatic encephalopathy
  • refractory ascites

(BRAIN = bili, refractory ascites, alb, INR, eNcephalopathy)

Co-morbidities

  • hepatorenal syndrome
  • variceal bleeding
  • SBP
  • hepatocellular carcinoma

CRITERIA FOR ACUTE TRANSPLANTATION (King’s College Criteria)

Paracetamol induced fulminant hepatic failure

  • pH < 7.3 or INR > 6 (PT > 100s)
    +
  • Cr > 300mmol/L
    +
  • grade III or IV encephalopathy

Non-paracetamol induced fulminant hepatic failure

  • INR > 6 (PT > 100s) or any 3 of the following variables:

(1) age < 10 or > 40 yrs
(2) aetiology – non A, non B hepatitis, halothane hepatitis, idiosyncratic drug reactions
(3) duration of jaundice before encephalopathy > 7 days
(4) INR > 3.5 (PT > 50s)
(5) bilirubin > 0.3mmol/L

CONTRAINDICATIONS

Absolute

  • severe infections/sepsis
  • extra-hepatic malignancy
  • severe cardiorespiratory disease
  • ongoing ETOH or drug use
  • AIDS
  • non-compliance

Relative

  • severe chronic renal disease (consider renal + liver transplant)
  • previous extensive biliary tract surgery
  • HIV positive
  • psychosocial issues

The following are NOT contra-indications:

  • hepatocellular carcinoma (up to 7cm)
  • hepatopulmonary syndrome
  • portopulmonary syndrome
  • portal venous thrombosis

COMPATIBILITY WORK UP

  • complicated!
  • recipient: disease state (urgency and severity), cardiorespiratory function, psychiatrist/social work, nephrologist, infectious diseases, dentist
  • weight of donor (BMI is a surrogate for fatty liver)
  • blood compatibility
  • investigations: CXR, Doppler sonography, selective angio/MRI, ECHO, cardiopulmonary testing, ECG, PFTs

PREOPERATIVE ASSESSMENT

Clinical Features

  • co-morbidities: diabetes, other organ dysfunction
  • jaundice
  • ascites
  • pleural effusions
  • cardiac failure
  • poor nutritional state
  • hepatorenal syndrome
  • portopulmonary syndrome (right ventricular failure from severe portal and pulmonary hypertension)
  • hepatopulmonary syndromes (hypoxaemia with intrapulmonary shunting)
  • cerebral oedema
  • bleeding (some subgroups are prothrombotic, e.g. Budd-Chiari syndrome)

Investigations

  • hyponatraemia
  • coagulopathy
  • hypoalbuminaemia
  • hypoglycaemia
  • low platelet count
  • fibrinolysis
  • anaemia
  • blood products; 10U cross-match, 12 FFP

MANAGEMENT OVERVIEW

  • correction of coagulopathy
  • high risk precautions
  • altered pharmacology: low first pass, Vd changed, increased free drug, enzyme dysfunction, slow metabolism and clearance

INTRAOPERATIVE MANAGEMENT

  • establish type of surgery: full transplant, sub-total, piggy-back, portal bypass, argon beam (blood sparing)
  • establish large bore IV access pre-induction (swan sheath, RICC line) -> expect massive blood loss
  • standard induction (RSI)
  • soft NG tube (beware of varices)
  • fulminant liver failure = raised ICP (manage accordingly)
  • invasive monitoring
  • venovenous bypass lines (femoral and RIJ -> 21Fr)
  • actively warm
  • transfuse RBCs:FFP (1:2)
  • monitoring coags frequently and TEG
  • maintain glucose with IV dextrose
  • monitor Ca2+ closely
  • use cell salvage
  • use anti-fibrinolytic (tranexamic acid 15mg/kg bolus -> 5mg/kg/hr)
  • haemodynamic instability from:

1. cardiac involvement (alcoholic cardiomyopathy)
2. pericardial effusion
3. systemic vasodilation

Stage 1 (Preparation)

  • prophylactic antibiotics
  • start SDD (selective digestive decontamination)
  • TXA2 (plasmin inhibitor)
  • laparotomy
  • dissection
  • slings placed around major vessels

Stage 2 (Anhepatic)

  • division of hepatic artery, portal vein, hepatic vein, bile duct
  • removal of liver and part of IVC -> anastomoses of donor and recipient vena cava and portal vein
  • venous return is severely compromised -> haemodynamic instability
  • keep Hb 60-80g/L
  • venovenous bypass (femoral to RIJ) to help
  • in acute hepatic failure patients may become hypoglycaemic
  • prednisolone 500mg IV

Stage 3 (Reperfusion)

  • re-establishment of blood flow through liver (portal vein to IVC)
  • post-reperfusion syndrome
    -> cytokine release, complement activation
    -> hypothermia, arrhythmias, hypotension, hyperkalaemia, bradycardia, cardiac arrest
    -> usually resolves <5 min, can last longer and need inopressors
    -> associated with: cold potassium-rich preservation fluids, long preservation times
  • hepatic artery re-anastomosis and bile duct reconstruction
  • will need inotropes

POST OPERATIVE

Key history in all transplant patients:

  • underlying diagnosis/ indication
  • type of transplant
  • medications and compliance (anti-rejection meds, anti-infectives, ulcer prophylaxis, other e.g. aspirin)

Key investigations to remember:

  • FBC, UEC, LFTs, Coags
  • Blood cultures (even without fever)
  • CMV PCR
  • drug levels
  • ultrasound (with doppler)

General

  • consider protective isolation (immunosuppressed)
  • aim for early enteral nutrition if no bowel anastomosis
  • avoid unnecessary moving of the patient initially, as liver may twist on vessels

Cardiovascular

  • keep Hb 60-80g/L
  • judicious fluid management (avoid hepatic oedema, impaired graft function)
  • inotropic support
  • avoid lactate containing fluids

Respiratory

  • aim for extubation early
  • pneumonia and TRALI common

Renal

  • optimal renal perfusion
  • urinary output measurement

Analgesia

  • PCA
  • RSC
  • paracetamol 0.5g QID

Medications

  • Cefuroxime 1.5g TDS – 3/7
  • Metronidazole 500mg TDS – if bilio-intestinal anastomosis
  • SSD regime
  • PPI
  • Immunosuppression (methylprednisolone, cyclosporine A, azathioprine, tacrolimus/sirolimus, monoclonal antibody therapy) – lower dose than other transplants as liver is relatively immunotolerant, about 10% of patients require no immunosuppression in the longterm

Haematology

  • platelets >50
  • heparin to APTT 40-60
  • blood products if bleeding

Graft Function

  • improving coagulation profile
  • decreasing transaminases
  • normal glucose
  • haemodynamic stability
  • adequate urine output
  • bile production (via T drain)
  • daily ultrasound to look for patency of blood flow
  • if concern about rejection -> liver biopsy (get ultrasound first)

COMPLICATIONS

Early – especially post-operative complications

  • bleeding/coagulopathy -> massive transfusion, hypocalcaemia
  • hypothermia
  • respiratory: hypoxia, pleural effusions, atelectasis, right hemidiaphragm palsy, TRALI, infections, pulmonary oedema
  • cardiovascular: haemorrhage, vasodilation, 3rd spacing
  • electrolytes and acid-base derangements
  • neurological: encephalopathy, cerebral oedema, central pontine myelinolysis
  • renal: may require RRT
  • small for size syndrome: hyperbilirubinaemia, graft dysfunction, ascites, portal hypertension, end-organ dysfunction
  • primary graft failure: fast decompensation, SIRS -> MODS
  • biliary leak -> collections, abscesses: check wounds and drains; use USS/ CT -> require OT or ERCP, Rx with ABX
  • biliary duct stricture -> altered LFTs (obstructive) -> OT or ERCP
  • hepatic artery thrombosis (often devastating): high fever, elevated LFT’s, graft failure, coagulopathy -> US doppler/CT angio -> thrombectomy, retransplant, angioplasty
  • portal vein thrombosis: hepatic dysfunction, massive ascites, renal failure, portal hypertension -> thombectomy, thrombolysis, endoscopic therapy
  • sepsis
  • hyperacute (rare) or acute rejection (day 7)

Late (>6 months) – longterm medical conditions and disease recurrence become important

  • sepsis due to immunosuppression (bacterial, viral (CMV, EBV), fungal, protozoal)
  • HTN
  • renal failure
  • chronic rejection
  • disease recurrence
  • DM
  • post-transplant lymphoproliferative disease (due to immunosuppression, and promoted by EBV)
  • malignancies
  • require immunisations: tetanus, diphtheria, influenza, pneumococcal, hepatitis A and B

SMALL FOR SIZE SYNDROME

  • occurs following transplant of reduced size graft, steatotic grafts, or if small donor or after partial hepatectomy
  • characterised by portal hyperemia and arteriolar constriction
  • hyperbilirubinemia, graft dysfunction, ascites, portal hypertension and MODS
  • management is controversial e.g. arterial vasodilators, treat/ prevent portal hypertension

References and Links

Textbooks and journal articles

  • Bersten AD, Soni N. Oh’s Intensive Care Manual (6th edition), Butterworth-Heinemann 2009. [Google Books Preview]

Social media and web resources


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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