Acute hepatic failure

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Acute hepatic failure PB Sherren ST7 ICM

Transcript of Acute hepatic failure

Page 1: Acute hepatic failure

Acute hepatic failure

PB Sherren ST7 ICM

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Learning Objective

• Understand the different types of Acute hepatic failure (AHF)• Acute Liver Failure (ALF)• Acute-on-Chronic Liver Failure (AoCLF)• Post-hepatectomy liver failure

• Appropriate therapies and support of the liver

• Role of transplantation and other advanced support

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ALF definition

Development of severe hepatic dysfunction within 6 months of the onset of symptoms in the absence of chronic liver disease• Acute Hepatitis with elevation AST/ALT• INR>1.5• Encephalopathy

Hyperacute, Acute or Subacute

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ALF

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Common causes of ALF

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AoCLF

Acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites +/- encephalopathy in a patient with previously chronic liver disease

Bil >85 μmol/L and INR >1.5 mandatory

AoCLF vs end stage CLF

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AoCLF

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Precipitants of AoCLF

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Post hepatectomy liver failure

Impaired ability of the liver to maintain its synthetic, excretory and detoxifying functions characterised by impaired coagulation and hyperbilirubinaemia on or after postoperative day 5.

50/50 definition - PT >50% and Bilirubin >50μmol/L

Grade A, B and C

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Caring for the liver patient

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Don’t forget the basics!

History and Examination

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Send bloods ++• FBC• Coag, fibrinogen, TEG/ROTEM• Biochemistry• LFTs and GGT• Paracetamol/salicylate level• Arterial ammonia• Blood gases (Lact/glucose)• β-HCG• Viral hepatitis serology• Autoimmune screen, copper and caeruloplasmin• AFP• HIV test

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Other investigations

• Liver US and doppler ASAP

• +/- CT/MRI

• Liver Bx?

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Management

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Good ICU Housekeeping• Stop hepatotoxic drugs• Optimise haemodynamics for oxygen delivery• Steriods?• CVC/Vascath/arterial line early with US. PAC?• Invasive ventilation +/- neuroprotection?• 30o head up• Early enteral nutrition (protein 1-1.5g/kg/day)• Stress ulcer prophylaxis (PPI)• Aperients• Antimicrobials• Glycaemic control

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Specific Rx

• Paracetamol – NAC• Budd Chiarri – Anticoagulation/TIPS• Autoimmune – Steroids• Acute Fatty Liver of pregnancy – Delivery

baby•Wilsons – Chelating agents• Lamivudine and Aciclovir

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Paracetamol OD• Common poisoning

• <1% cases of OD result in significant hepatotoxicty

• CYP450 convert paracetamol to NAPQI

• NAPQI EXTREMELY hepatotoxic

• Usually conjugated with hepatic glutathione

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Paracetamol OD

• Bad• Malnutrition, ETOH abuse, enzyme inducing drugs• Large staggered OD• Delayed presentation and initiation of NAC

• N-acetylcysteine augments glutathione levels

• NAC highly effective if delivered within 8-12hrs

• Prescott normogram used to determine risk

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Cardiovascular• Hyperdynamic and hypervolaemic

•Moderate incidence adrenal dysfunction

• CO monitoring and fluid responsiveness

• PAC • Right ventricular cardiomyopathy• Hepatopulmonary shunt and pulm Ht

• Noradrenaline

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Variceal bleed• Restore Blood volume• Correction of coagulopathy• Reduce portal vascular resistance• Terlipressin/octreotide• 5/7 Abx (Tazcoin/cephalosporin)

• PPI?• OGD• Banding• Glue• Stenting

• Sengstaken• TIPS

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Coagulopathy• Coagulation• Low fibrinogen• Low levels of II, V, VII, IX, X, APC, Protein C/S• Mixed fibrinolytic/antifibrinolytic effects

• ‘Auto-anticoagulation’ vs prothrombotic• NO routine correction of INR (incl for lines)• Thromboelastometry helpful (TEG vs ROTEM) • Everything changes if bleeding • Generally platelets/fib 1st• FFP/cyro vs PCC/FCC• TXA and Calcium

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Ventilation

• Hepatopulmonary syndrome and shunting• Pulmonary hypertension may need ↓PVR• IAH/IACS

• Early intubation for Grade III/IV HE• Neuroprotection vs standard ARDsnet• LRTI/VAP common, low threshold for Abx• Consider paracentesis in IACS

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Encephalopathy and cerebral oedema

• Common in ALF and grade III/IV HE and NH4 >150• Cytotoxic and vasogenic/hyperaemic in origin• Poor autoregulation• ICP>25mmHg and CPP<50mmHg bad prognosis• Sepsis/SIRS detrimental• Reverse Jugular venous oximetry • ICP bolt risk vs benefit• TBI like ICP management• NO evidence for neuromonitoring• CRRT/plasma exchange

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Hepatorenal Syndrome• Not the commonest cause of AKI in AHF• ATN/nephrotoxic drugs/glomerulonephritis/IACS

• HRS diagnosis of exclusion• Type 1 vs Type 2• Results from reduced perfusion• Splanchnic vasodilation• Poor autoregulation • ↓ renal prostaglandin synthesis and other vasoactive mediators

• HAS/terlipressin• Early CRRT

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Renal Replacement Therapy• Haemofiltration vs HD/HDF?

• Some low level evidence for NH4+ clearance

• Start early

• Esp if Grade III/IV HE and NH4+>150

• Aim for dose of 35ml/kg/hr (Calculated vs actual dose received?)

• No evidence for high volume haemofiltration

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Microbiology• Highly susceptible to infection (LRTI/SBP/urinary/lines/wounds)

• SIRS/hyperdynamic/endotoxin translocation vs Bacteraemia

• Proven rates of 80% bacterial and 30% fungal

• Gram +ve in 1st 3-4 days followed by gram –ve and fungal infections

• Prophylaxis offers no mortality benefit

• Maintain high vigilance

• Refer to local guidelines and micro team

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ALF transplant Criteria• Paracemol vs non paracetamol• King’s college criteria

• Paracetamol• pH <7.3 >24hrs post overdose• Grade III/IV HE + Creat >300 + PT >100s

• Non Paracetamol• pH <7.3 or PT >100s• HE III/IV with any 3 of the following

• Age <10 or >40• Bil >300• Jaundice to HE time <7 days• PT >50s• Seronegative hepatitis or drug induced

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Transplant• Multidisciplinary decision

• Specialised service managed at supraregional centres

• If in doubt=refer/discuss

• Outcomes from transplant depend on ALF vs AoCLF vs CLF

• Live donor vs DBD vs DCD. Orthotopic and Domino Tx

• Complex anaesthetic+++

• Protocolised ICU post op management • TEM guided coagulation (balance bleeding vs HA/anastomosis flow)• Antibiotics• Immunomodulation• Early US and dopplers• MDT approach

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Artificial Liver Support• Bridge to transplant or recovery?

• Evidence?

• Detoxifying systems• Albumin dialysis• MARS (albumin dialysis/detoxifying and de-ionising columns)• Plasmaphoresis with FFP promising in ALF

• Bioartificial Systems• Extracorporeal liver perfusion old technology• Other systems using hepatocytes• ELAD study pending publication

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Questions?

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Conclusion

• Don’t forget the basics• Resuscitate the patient • Good ICU house keeping• ALF vs AoCLF vs CLF• Antidotes/Specific Rx where appropriate• Complex/systemic disease with multi-organ

effects • EARLY referral/discussion with a liver unit