Acute liver failure resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Vendhan Ramanujam M.B.B.S [2]

Definitions

Acute Liver Failure

Evidence of coagulation abnormality (INR ≥1.5) and any degree of alteration in mental status in the absence of pre exisiting chronic liver disease, cirrhosis and any illness of <26 weeks duration is defined as acute liver failure. Few exceptions that are included in spite of their presentation with cirrhosis are Wilson disease, vertically-acquired HBV, and autoimmune hepatitis if they have been recognized for <26 weeks. When the above presentation duration is up to 26 weeks, acute liver failure is the better terminology to be used when compared to terms like fulminant hepatic failure, fulminant hepatitis or necrosis, hyperacute, acute and subacute liver failure.

Hepatic Encephalopathy

Based on their clinical manifestation, different grades of hepatic encephalopathy are defined as follows

Grades	Clinical Features
I	Changes in behavior, minimal changes in level of consciousness
II	Inappropriate behavior, gross disorientation, drowsiness, possibly asterixis
III	Marked confusion, incoherent speech, mostly sleeping but arousable to vocal stimuli
IV	Comatose, unresponsive to pain, decorticate or decerebrate posturing

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Cocaine
• Idiosyncratic hypersensitivity reactions
• Mushroom poisoning
• Shock or hypoperfusion

Common Causes

• Autoimmune hepatitis
• Acetaminophen toxicity
• Viral hepatitis
• Shock or hypoperfusion

Do's

General Management

• At transplant center, place the patient immediately on the transplant list if progression of the disease is rapid
• During initial evaluation
  • In detailed H/o: Include H/o viral infection exposure, drug and toxin intake
  • In detailed PE: Look for stigmata of chronic liver disease
  • In lab tests: Calculate bilirubin:alkaline phosphatase ratio if Wilson disease suspected (e.g., in patients <40 years without obvious explanation for ALF). Include hepatitis E virus serology in migrants from endemic region.
• During monitoring for cerebral edema and increased ICP
  • Include ICP monitoring when patient meets all eligible criteria for liver transplantation, encephalopathy is grade IV, CT head is consistent with edema without hemorrhage, PT is corrected to INR <1.5, and platelet count >100,000/mm3
  • Rule out or correct coagulopathy
  • Rule out intracerebral hemorrhage and other intracranial causes of altered mental status with CT head
  • ICP monitors are placed preferably in subdural space in OR
  • Other methods of monitoring that are in various stages of evaluation are transcranial doppler ultrasonography, near-infrared spectrophotometry, and measurement of serum S-100 beta and neuronal specific enolase
  • Target values during monitoring: ICP <20-25 mmHg and CPP 50-60 mmHg
• Administer 3% NS at 0.1-1 ml/kg/hr i.v infusion to prevent cerebral edema and increased ICP. Maintain serum sodium between 145-155 mEq/dL and hold if serum osmolality is >360 mOsm/L
• For coagulopathy prevention
  • Administer 5-10 mg of Inj. Vitamin K SC
  • Administer cryoprecipitate if serum fibrinogen <100 mg/dL
  • Maintain platelet count around 20,000/mm3
• While avoiding drugs, specifically avoid aminoglycosides
• Prophylactic antibiotics (Cefotaxime: 100-200 mg/kg/day i.v; every 6-8 hours/ If allergic to penicillin, meropenem: 20-40 mg/kg i.v; every 8 hours/ Flucanazole: 3-12 mg/kg i.v; daily/ In case of catheter related sepsis and suspected MRSA, vancomycin: 40 mg/kg/day i.v; every 6-8 hours) when
  • Infectious surveillance is positive
  • Encephalopathy is progressing to grade III/IV
  • There is gastrointestinal bleeding
  • Hypotension is refractory
  • Components of systemic inflammatory response syndrome (SIRS) are present
• For anticipated acetaminophen toxicity administer NAC: 150 mg/kg IV over first 1 hour, 50 mg/kg IV over next 4 hours, 100 mg/kg IV over next 16 hours, 150 mg/kg IV over next 24 hours. Thereafter administer 70 mg/kg PO daily until discharge or transplantation
• To avoid nutritional deficiency include
  • Eternal feeding
    • Protein 60 g/day
    • Hold if ammonia >200 mcg/dL
  • If eternal feeding is contraindicated, start parental feeding
    • IV D10 1/4 NS, maintain sodium <3 mEq/kg/day
    • Protein 0.5 g/kg/day
    • Hold if ammonia >200 mcg/dL

Etiology Specific Management

• Acetaminophen or suspected acetaminophen toxicity:
  • Administer activated charcoal (1g/kg PO) within 1 hour after drug ingestion. May be beneficial even when administered within 3-4 hours after ingestion.
  • Plot a nomogram that helps determining the likelihood of serious liver damage, but does not exclude possible toxicity
  • Administer NAC within 8 hours, beneficial even when administered within 48 hours after drug ingestion
    • 140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h (17 doses) or
    • 150 mg/kg in 5% dextrose IV over 15 minutes, then maintenance dose of 50 mg/kg IV over 4 hours and then 100 mg/kg IV over 16 hours
    • Anticipate allergic reactions
• Autoimmune hepatitis:
  • Administer 40-60 mg/day of prednisolone
  • While on steroids, prepare the patient for transplantation
• Budd-Chiari:
  • Rule out malignancy and malignancy associated coagulopathy before transplantation
• Malignant infiltration:
  • Look for carcinoma of breast, small cell carcinoma of lung, lymphoma and melanoma
• Mushroom poisoning:
  • Penicillin G (300,000 1 MU/kg/day)
  • Europe and South America: Silibinin or silymarin; North America: Milk thistle
• Viral:
  • Positive HBsAg: Possible reactivation, so administer lamivudine or adefovir x 6 months
  • Pregnancy and immunocompromised patients: Suspect herpes, so confirm with liver biopsy and administer acyclovir

Complication Specific Management

• Ascites:
  • Administer lasix (160 mg) and aldactone (400 mg) at 1:2.5
• Cerebral edema and increased ICP:
  • Mannitol: 0.5-1 g/kg; once or twice daily; hold if serum osmolality is >320 mOsm/L
  • Hyperventilate to PaCO2 of 25-30 mmHg
  • 3% NS: 0.1-1 ml/kg/hr; maintain serum sodium between 145-155 mEq/dL; hold if serum osmolality is >360 mOsm/L
• Coagulopathy:
  • Platelet transfusion until platelet count >50,000/mm3
  • rFVIIa: 40 mg/kg IV
• Hemodynamic instability:
  • Fluid resuscitation with target mean arterial pressure 50-60 mmHg and target CPP 60-80 mmHg
  • Add hydrocortisone in case of septic shock
• Grade II hepatic encephalopathy:
  • Add short acting BZD only when there is unimmaginable agitation
  • Ammonia >200 mcg/dL:
    • Lactulose 30-45 mg/d PO; 3-4 times a day
    • Target <50 mcg/dL
  • Persistently ammonia >50 mcg/dL:
    • Neomycin <12y≥ rifaximin
  • Persistently ammonia >200 mcg/dL:
    • Continuous venovenous hemodialysis for 3-4 hours
• Renal failure:
  • Continuous venovenous hemodialysis following symptomatic uremia, untraceable hyperkalemia and metabolic acidosis
• Add neurology, neurosurgery, hepatology, nephrology and transplant surgeon consult as needed.

Dont's

• Do not use penicillamine in the treatment of acute liver failure caused by Wilson disease.
• Stop administering mannitol if serum osmolality is >320 mOsm/L.
• Stop administering 3% NS if serum osmolality is >360 mOsm/L.
• Do not use sedatives in encephalopathy except during unimmaginable agitations during grade II hepatic encephalopathy.

References

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