FRCA Notes

Chronic liver disease

The curriculum is conscise regarding this topic: 'Demonstrates knowledge of hepatic failure'.

A March 2021 CRQ on sedation in liver disease (69% pass rate), saw examiners lament poor answers on 'the effects of liver disease on cardiovascular/respiratory systems & pharmacokinetics'.

In a CRQ topic on 'liver disease' from September 2022 (77% pass rate), candidates 'struggled with the pharmacological component of the question.'

Resources

  • Liver disease encapsulates a spectrum of pathological processes that cause impaired hepatic synthetic or metabolic functions

  • Chronic liver failure is the progressive deterioration of hepatic function over a period >28 weeks
  • As the disease progresses, a cyclical process of liver parenchyma inflammation - destruction - regeneration ensues
  • This subsequently leads to fibrosis, distortion of normal hepatic architecture and cirrhosis

  • Any cause of acute liver failure could lead to chronic failure, but typically alcohol, viral hepatitis, autoimmune hepatitis or metabolic liver disease is responsible
  • Liver disease can be classified according to aetiology, but perhaps more commonly it is done so temporally

Acute liver failure

  • This triad of jaundice, coagulopathy and encephalopathy describes new onset liver injury in a patient without pre-existing liver disease/cirrhosis
  • It can be further sub-classified using the O'Grady system, which describes the disease in terms of time from jaundice to encephalopathy
    • <7 days = hyperacute
    • <28 days = acute
    • <12 weeks = subacute
  • It is covered further in the ICM section of the site (see link above)

Chronic liver failure

  • A progressive deterioration of hepatic function over a period >28 weeks

Acute-on-chronic liver failure

  • A syndrome of rapid onset hepatic (and extra-hepatic) organ dysfunction in the context of known chronic liver disease
  • Characterised by severe, systemic inflammation and extra-hepatic organ failure
  • Carries a high 28-day mortality
  • Acute decompensation can occur due to a number of factors, such as:
    • Vascular e.g. hypovolaemia or hypotension, variceal bleeding
    • Infection inc. SBP, flare of hepatitis, new infection
    • Impaired homeostasis e.g. electrolyte or fluid imbalance from diuretic drugs, drinking
    • Excessive dietary protein

Respiratory

  • Mechanical compression of the lungs from hepatomegaly/ascites leads to alveolar hypoventilation, atelectasis and reduced FRC
  • Hepatic hydrothorax
  • Transudative pleural effusions

  • Hepato-pulmonary syndrome (up to 20%)
    • Release of hepatic endothelin-1, as well as other vasoactive molecules such as NO and CO, causes aberrant pulmonary vasodilation
    • Consequent intra-pulmonary arteriovenous shunting and enhanced angiogenesis leads to:
      • Dyspnoea
      • Orthodexia
      • Hypoxaemia

  • Porto-pulmonary hypertension syndrome (4 - 6%)
    • A pulmonary hypertension arising due to:
      • Impaired metabolism of pulmonary vasoconstrictors
      • Vascular remodelling due to hyperdynamic pulmonary circulation and therefore increased shear stress
      • Increased circulating inflammatory cytokines
      • Thromboembolic phenomena arising from the portal circulation
    • Associated with a high mortality

Cardiac

  • High cardiac output and low SVR = hyperdynamic circulation
  • Relative hypovolaemia due to vasodilation in systemic and splanchnic vasculature
  • Cardiomyopathy may be alcoholic, cirrhotic or from infiltrative disease e.g. haemochromatosis
  • Cirrhotic cardiomyopathy
    • Diastolic dysfunction + prolonged QTc + blunted contractile response to stress

Neurological

  • Hepatic encephalopathy
    • A reversible neuropsychiatric abnormality
    • Caused by decreased neurotoxin metabolism within the liver; ammonia, short-chain fatty acids and mercaptans
  • Grading:
    • Grade Description
    I Confused
    II Inappropriate, drowsy
    III Stuporous but rousable, very confused or agitated
    IV Coma

Renal

  • AKI leading to CKD
    • A blend of pre-renal and intrinsic renal in nature

  • Hepatorenal syndrome
    • A reduced and declining GFR in a patient with advanced liver disease
    • It is defined by a Cr >133μmol/L in a patient with cirrhosis and ascites, of no other possible aetiology
    • Caused by generalised vasodilation (NO, CO, endothelin-1) and hormone release (RAAS, ADH, catecholamines) which subject the kidneys to hypotension, hypovolaemia and vasoconstriction
    • Classified into two types by speed of onset:
      • HRS Type 1 - rapidly progressive (<2 weeks), severe deterioration typically triggered by some inciting event which often causes decompensation of the existing liver disease too
      • HRS Type 2 - slowly progressive and more moderate deterioration in renal function - patients often have refractory ascites

Gastrointestinal

  • Portal hypertension (>10mmHg)
    • Increased pressure gradient between portal vein and hepatic veins
    • Manifests as varices, splenomegaly and ascites
  • Spontaneous bacterial peritonitis

Nutritional and metabolic

  • Malnutrition
  • Muscle wasting/sarcopaenia
  • Impaired wound healing
  • Hypoglycaemia
  • Hypoalbuminaemia

Haematological - coagulopathy

  • Patients historically thought to be at high risk of bleeding
    • There may certainly be anaemia following GI blood loss
  • More recent evidence suggests patients exist in a dynamic, altered balance of pro-coagulant and anti-coagulant factors
  • The loss of anti-coagulant factors is offset by alterations in pro-coagulant factor synthesis
  • The INR provides a poor representation of haemostatic balance and risk of bleeding in these patients
Pro-coagulant factors Anti-coagulant factors
↑ vWF ↓ platelet number (splenic sequestration & reduced thrombopoietin)
↓ ADAMTS-13 ↓ Factors II, V, VII, IX, X and XI
↑ Factor VIII Vitamin K deficiency
↓ Protein C&S Hypofibrinogenaemia
↓ Antithrombin III ↑ t-PA
↓ Plasminogen

Endocrine

  • Adrenal insufficiency
  • Secondary hyperaldosteronism
    • Water retention
    • Hyponatraemia

Perioperative management of the patient with chronic liver disease


  • Surgery in patients with chronic liver disease carries high morbidity and mortality
  • They are at an increased risk of multiple complications; bleeding, infection, impaired wound healing, AKI, hepatic decompensation
  • As such, the decision to perform surgery should be weighed carefully and appropriate risk assessments should take place

History and examination

  • One should establish
    1. Aetiology and severity of liver disease
    2. Presence and degree of extra-hepatic manifestations of chronic liver disease
    3. Degree of compensation, or the presence of acute-on-chronic liver disease

  • Other facets of management will be determined by disease-specific aspects e.g. perioperative steroid replacement in patients with autoimmune hepatitis
  • Examination should elicit
    • Stigmata of liver disease e.g. jaundice, caput medusae, spider naevi, hepatosplenomegaly, asterixis, encephalopathy
    • Signs that may compromise anaesthesia e.g. large volume ascites, pleural effusions

Investigations

  • Bloods should include FBC, U&E, LFT and coagulation profile including fibrinogen and TEG/ROTEM
  • CXR ± lung function tests
  • ECG
  • TTE if concerns re: cardiomyopathy
  • CPET testing
  • Once can measure the hepatic venous pressure gradient to assess the degree of portal hypertension

Risk assessment

  • There is no universally accepted scoring systems to assess patients with chronic liver disease prior to surgery
  • Surgical factors, such as degree of urgency and risk of perioperative bleeding, will influence outcome

  • Child-Turcotte-Pugh Score
    • A familiar score using bilirubin, albumin, INR, severity of encephalopathy and ascites
    • It predicts post-operative morbidity and mortality for both hepatic and extra-hepatic intra-abdominal surgery

    Score Child-Pugh Grade Perioperative Mortality
    5 - 6 A <5 - 10%
    7 - 9 B 25%
    10 - 15 C >50%

  • Other scores include:

  • Emergency surgery, unless life- or limb-threatening, should be deferred to allow optimisation ± transfer to a tertiary liver centre
  • Elective surgery depends on the patients clinical condition and risk score:
    • Acute liver failure or injury → defer or cancel surgery, use alternative non-surgical management
    • Child-Pugh A (MELD <10) → optimise and proceed with caution
    • Child-Pugh B (MELD 10 - 15) → optimise ± proceed with caution
    • Child-Pugh C (MELD >15) → defer or cancel surgery, use alternative non-surgical management

Optimisation

  • Optimisation will be based on which extra-hepatic manifestations of chronic liver disease are present

    • Respiratory

  • Consider pleural aspiration for pleural effusions that compromise respiratory function (hepatic hydrothorax)
  • Reduce pulmonary artery pressures and PVR e.g. PDE-inhibitors, prostacyclin analogues, endothelin antagonists (porto- or hepato-pulmonary hypertension)

    • Cardiac

  • Optimise fluid balance
  • Optimise RV function (porto- or hepato-pulmonary hypertension)
  • Consider β-blocker in cirrhotic cardiomyopathy or portal hypertension (e.g. propranolol to reduce portal pressures)

    • Neurological

  • Aggressively treat infection contributing to encephalopathy (low threshold to treat fungal infection)
  • Dietary protein restriction may aid encephalopathy
  • Use laxatives, rifaximin and/or haemofiltration to reduce ammonia
    • Lactulose acidifies the gut, converting ammonia to non-absorbable ammonium
  • Correct electrolyte abnormalities

    • Renal

  • Remove risk factors for AKI e.g. fluid balance issues, nephrotoxic drugs
  • Consider use of albumin and terlipressin in hepato-renal syndrome

    • Gastrointestinal

  • If hepatic portal venous gradient >10mmHg consider TIPS
  • Consider prophylactic variceal ligation
  • Treat ascites with salt/water retention, diuretics, paracentesis + albumin, or TIPS if refractory
  • Consider prophylactic Abx in patients with history of SBP

    • Nutritional and metabolic

  • Optimise glucose control
  • Perioperative nutritional supplementation, including trace elements/vitamins

    • Haematological

  • Limit excessive use of blood products and use viscoelastic assays to guide transfusion
  • Consider vitamin K or PCC
  • No evidence for routine use of FFP to correct INR and reduce bleeding risk in cirrhotic patients prior to elective procedures; may cause hypercoagulable state
  • Correct anaemia to Hct >0.25
  • Consider platelet transfusion if <50x109/L
  • Consider cryoprecipitate if fibrinogen <1.0g/L

Monitoring

  • Close monitoring of haemodynamics and organ perfusion is required owing to:
    • Altered haemodynamics associated with chronic liver disease
    • Fluid shifts secondary to drug-induced vasodilation or ascitic drainage
    • High risk of post-operative AKI and hepatorenal syndrome

  • AAGBI
  • Invasive BP monitoring
  • Wide bore cannulae, with access to rapid transfuser, if high blood loss anticipated
  • Low threshold for CVC, especially in major surgery
  • ± Cardiac output monitoring, bearing in mind that oesophageal varices are a contraindication to oesophageal Doppler

Choice of technique

  • Liver disease in the absence of coagulopathy is not a contraindication to neuraxial anaesthesia
  • No strong evidence to support routine use of neuraxial over general techniques; both can cause hypotension and impair hepatic & renal blood flow
  • Intra-operative hypoxia is common, owing to the presence of pleural effusions and/or hepatopulmonary syndrome
    • This may make GA preferable in order to optimise ventilation

Anaesthetic drug choices

  • Hepatic impairment will affect performance of most anaesthetic agents
  • In general, reduced doses of short-acting agents with minimal hepatic metabolism are preferred
  • No strong evidence volatile or TIVA is superior; naturally avoid halothane and its hepatitis-inducing ways

Fluid management

  • Use warmed, balanced crystalloid guided by dyanmic responsiveness indicies to replace fluid loss in the first instance
  • Viscoelastic haemostatic assays should guide use of FFP, cryoprecipitate or fibrinogen
  • HAS may be used for volume expansion
  • RBCs may be required, although the volume of transfusion correlates directly with post-operative complications and mortality

Opioid analgesia

  • Remifentanil may be the safest opioid as muscle/RBC esterases are preserved in patients with hepatic disease
  • Fentanyl is the preferred post-operative opioid (inc. as PCA) as it has no active metabolites and is renally excreted
  • Oxycodone is an alternative option

  • Morphine's elimination is delayed and should be used with caution
  • Alfentanil, although short-acting, suffers in hepatic disease from:
    • Reduced plasma protein binding due to reduced ɑ1-acid glycoprotein concentrations
    • Lower rate of elimination due to increased volume of distribution

Care bundle

  • Prophylactic antibiotics
  • Maintenance of normothermia
  • Close monitoring of glycaemic state; avoid hypoglycaemia

Analgesia

  • Reduced-dose paracetamol can be used safely (unless it is the precipitant cause of acute liver injury)
  • Avoid NSAIDs due to risk of nephrotoxicity, GI bleeding and altered platelet function
  • Utilise regional anaesthetic techniques
  • Fentanyl and oxycodone may be the most appropriate opioids if carefully titrated

Disposition

  • HDU/ITU post-operative unless well-compensated disease (Child-Pugh A) and only a minor procedure
  • Close monitoring for:
    • Signs of decompensation (ascites, jaundice, encephalopathy, coagulopathy)
    • Glucose levels
    • Renal function
    • Sedation level in the context of opioid analgesia

Other

  • VTE prophylaxis on an individual basis; high INR does not preclude patient being in a hypercoagulable state
  • Laxatives to reduce risk of hepatic encephalopathy e.g. lactulose 20-30ml QDS
  • Aggressive treatment of (typically Gram-negative) sepsis if it develops