Asian Intensive Care: problems & solutions
International Intensive Care conference, Hong Kong, November 28th-30th 2007
Click here for details

Management of patients with liver impairment presenting for surgery

Management of patients for liver transplantation

Halothane hepatitis

Further reading

• largest organ in body
• 25% of cardiac output (about 1.5l/min)
• dual blood supply: 30% via hepatic artery and 70% via hepatic vein
• hepatic blood flow:

• Metabolism of nutrients (Glucose, lipids, chol, bile acids,protein)
• Bio-synthesis (Albumin, globulins, clotting factors, TG’s, Chol, lipoproteins)
• Bio-transformation
• Haem metabolism and bile production
• Drug and toxin metabolism
  PHASE I : - in Zone 3 of lobule – Centrilobular – lowest O2 saturation
  - alteration of intrinsic molecular structure
  - OXIDATION/ REDUCTION/ HYDROLYSIS
  PHASE II: - in Zone I – Periportal – highest O2 saturation
  - conjugation with second substance to increase polarity)
• Reticulo-endothelial system (10% liver mass is Kuppffer cells)
• Storage (Glycogen, proteins, vitamins A, D, B12, K, Copper)

Usually disrupted due to:

• reduced hepatic blood flow
• porto-systemic shunting
• impaired metabolic activity
• lowered albumin
• changes in Vd
• altered receptor kinetics
• decreased renal function
• changes in BBB

Drugs with HIGH EXTRACTION RATIO (>0.7) depend on hepatic blood flow – e.g. MORPHINE, PETHIDINE, PROPRANOLOL, GTN

Therefore reduce dose but not frequency of dosing

Drugs with LOW EXTRACTION RATIO (<0.3) depend on metabolic capability of liver – e.g. BDZ, WARFARIN, THEOPHYLLINE

Therefore lengthen time between dose administration, but not dose

? risk factors

? clinically icteric, signs of liver failure, hepatomegaly

Look specifically for:

• ascites. Indicates advanced hepatic disease and should be controlled prior to surgery although diuresis can produce its own problems. Note that hyponatraemia may be due to excess water retention or total body depletion of sodium secondary to diuresis
• hypoxaemia. Due to: ventilation-perfusion mismatch, pleural effusions (low colloid oncotic pressure) and abnormal basal pulmonary capillary vasodilation.
• CVS instability. Advanced liver disease associated with combination of increased cardiac output, decreased peripheral vascular resistance and decreased cardiac reserve
• GI bleeding. Portal hypertension predisposes to oesophageal varices and upper GI bleeding – acute bleeding needs aggressive resuscitation (with blood + FFP + cryoprecipitate + platelets) +/- OGD & injection of varices +/- octreotide infusions +/- Sengstaken tube placement +/- surgery as a last resort. May also be chronic bleeding.

• esp. USS, OGD, ERCP, CT

• AST, ALT – no correlation between levels and damage

• Conjugated bilirubin, gamma-GT, Alk Phos

• Albumin (half life >20days)
• Pre-albumin (half life ~1.5days)
• Clotting factors V, VII, (half life ~ 1.5days)
• Prothrombin time increases

Patients have abnormal haemostatic function because of:

• decreased platelet count
• decreased platelet adhesiveness
• decreased synthesis of clotting factors
• qualitative alterations in clotting factors
• circulating fibrinolysins (sometimes present)
• rarely DIC

Vitamin K rarely helpful in patients with advanced liver disease.

• based on Child's score:

• incidence of post-operative renal failure increased by 3 pre-operative factors:
• high bilirubin (> 120 mcmol/l),
• Gm -ve bacteraemia,
• hypokalaemia. Clearly latter factor exacerbated by diuretics and co-existing metabolic alkalosis.

• Difficult because:
• abnormal clotting may preclude regional technique
• raised intra-abdominal pressure may restrict positioning of patient

Probably safest:

• Induce with propofol (CARE: with CVS instability)
• Intubate and use IPPV as pre-op V/Q mismatch and raised intra-abdominal pressure may exacerbate hypoxaemia
• If performing a rapid sequence induction, be aware that probable reduced plasma cholinesterase concentration may prolong suxamethonium activity
• Use atracurium as metabolism is via Hoffman degradation
• Use inhalational agents not significantly metabolised (e.g. isoflurane)
• Use opioids at lower doses
• Use local anaesthetic agents at lower doses
• Invasive monitoring essential (IABP, CVP, +/- PAFC)
• Maintain good diuresis (>50mls/hr), but avoid Na+ rich fluids

Consider ICU care post op, but keep ventilated for as short a time as possible, as IPPV and PEEP decrease hepatic blood flow

HOMOGRAFT - same species

ALLOGRAFT - same individual

XENOGRAFT - other species

ORTHOTOPIC – site occupied by native organ

HETEROTOPIC – adjacent, or remote, from native organ

• Brainstem death diagnosed
• No known contraindications:
• HIV/HBV/HCV infection (??homosexuality)
• Known active viral infection
• IVDA
• Malignancy (excl. Iy CNS tumour)
• Bacterial sepsis
• DM with target organ involvement
• Prolonged cardiac arrest with organ damage
• Age: 1 month - 65 yrs

Needs coordination of:

• donor team
• retrieval team
• recipient team

HENCE need for transplant coordinators

• aim is to keep organ out of body for as short as time as possible, in as physiologically normal state as possible.
• Use of solutions e.g. University of Wisconsin solution to bathe organ during transfer:

• has end stage disease. Most common cause is paracetamol overdose
• exclusions similar to those for donors ( HIV etc)
• immunosuppressed state – usually with Cyclosporin, but predisposes to infections (both bacterial, opportunistic and reactivation of latent viruses [e.g. herpes zoster]) and malignancies (esp. sarcomas and lymphomas)

Should include correction of :

• coagulopathy
• fluid resuscitation
• metabolic imbalance

• induce with propofol (carefully)
• paralyse with atracurium
• maintain with N20 / O2 / Isoflurane
• opioid analgesia per- and post op
• INVASIVE MONITORING – ALL lines put in under strict asepsis
• Correct coagulopathies aggressively – use of TEG per-operatively
• Maintain urine output
• "Rule of 100’s":
• SYS BP >100mmHg
• Urine output >100mls/hr
• PaO2 > 100mmHg (13Kpa)
• Hb > 100g/l

ICU post-op, paying particular care to signs of:

• hepato-renal syndrome
• sepsis
• rejection:
  • rising liver trans-aminases and bilirubin
  • fever, raised WCC, CVS instability

Usually triple therapy:

• CORTICOSTEROIDS (induces lipocortin which inhibits phospholipase A2, therefore decreasing COX activity, and decreasing PG’s, TXA-A2, Prostacyclins. Mainly act on polymorphs and macrophages. Side effects: PUD, Cushing’s syndrome, glucose intolerance, hypertension and hypokalaemia, adrenal suppression and osteoporosis)
• AZATHIOPRINE (converted to mercaptopurine, which acts as an antimetabolite and inhibits DNA synthesis. Side effects: bone marrow suppression [anaemia / thrombocytopaenia / granulocytopaenia] hepatic fibrosis / pulmonary infiltrates)
• CYCLOSPORIN A (obtained form soil fungi and inhibits T-cell proliferation and cell mediated immunity. Side effects: nephrotoxicity / hepatotoxicity / neurotoxicity / hirsutism / hypertension / skin rashes).

Anaesthetising a post liver transplant patient for an unrelated surgical procedure, requires full pre-op assessment as usual. Anaesthetise the patient as if they had liver impairment (i.e. care with fluids, strict asepsis for lines and maintenance of good urine output). Also, discussion with team where patient had original transplant performed prior to anaesthesia, as transfer of patient pre-op may be appropriate.

First reported 1958

Incidence is controversial. Less common in children, more common in obese females, with repeated exposure to halothane anaesthetics. ??Genetic predisposition??

A history of unexplained pyrexia or jaundice following halothane exposure is contra-indication to future use.

Hepatitis reported with: Halothane >> Enflurane >> Isoflurane (only one case isoflurane hepatitis reported)

2 types of hepatic damage:

MILD:

• Incidence ~5 – 20%.
• Occurs 1 – 3 days post exposure.
• Mild elevation in liver transminases.
• Usually asymptomatic

SEVERE:

• Incidence 1 in 6,000 to 1 in 30,000.
• Occurs 5 – 15 days post exposure. Mortality of 50 – 80%.
• Mechanism of action??:
  • direct reduction in hepatic blood flow causing transient hepatic hypoxia and therefore switch of halothane metabolism from oxidative pathway to reductive pathway. Production of Tri-fluoro-acetyl halide (TFA) which acts as a hapten, stimulating cell mediated immune response (Type IV hypersensitivity) and fulminant hepatic failure

CSM recommendations (1986)

Avoid halothane in patients:

• who have had a halothane anaesthetic in last 3 months
• who have had a previous episode of unexplained jaundice or pyrexia following halothane exposure
• who have had a previous exposure and had previous adverse reactions

With the advent of newer inhalational anaesthetic agents and TIVA, halothane is becoming obselete, and therefore the incidence of halothane hepatitis is falling

• Brown BR. Liver disease. Current Opinions in Anaesthesiology 1991: 4: 430-2
• Calvey TN. and Williams NE. Principles and Practice of Pharmacology for Anaesthetists. Blackwell Science
• Elliot RH, Strunin L. Hepatoxicity of volatile anaesthetics. Br. J. Anaesth. 1993: 70; 339-48
• Epstein M. The hepatorenal syndrome – newer perspectives. N Eng J Med. 1992; 327: 1810-1
• Hayes PC. Liver disease and drug disposition. Br. J. Anaesth. 1992: 68: 459-61

© Peter Dzendrowskyj October 1999

Forthcoming BASIC courses: February - London, Kuala Lumpur; March - Hawkes Bay, Sun City; April - Beijing, Brisbane
Click here for details

©Charles Gomersall, March, 2007 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
Copyright policy    Contributors