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

• Free EM Talks — Julia Weldon: Management of liver transplant (2011)
• Free EM Talks — Brian Lin: The Liver Transplant Patient – What’s Different (2011)
• Free EM Talks — Rob Rogers: Transplant Patients in the ED (2004)