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

Management

Altered mental status & PT prolongation by 4-6 sec or INR ≥1.5 presenting w/ nonspecific abdominal Sx w/o preexisting chronic liver disease, cirrhosis & any illness of <26 wks duration

Acute liver failure

Mandatory hospital admission

w/o altered mental status, significant coagulopathy & abnormal LFT

w/ altered mental status

High dependency ward admission

Worsening mental status

ICU admission

w/ or progression to grade I/II hepatic encephalopathy

Transfer to transplant center

Initial evaluation: Detailed H/o and PE Labs: CBC, PT/INR, serum BCH, ABG, ammonia, acetaminophen & tox screen for other drugs/toxins, viral serology (A-E), autoimmune markers, amylase, lipase, bilirubin:alkaline phosphatase, blood grouping & typing, HIV status

General management

Etiology specific management

Complication specific management

General Management

Continuous monitoring under quite environment w/ preventive treatment strategies

Cerebral edema & increased ICP

Coagulopathy

Drugs

GI bleeding

Hemodynamic instability

Hepatic encephalopathy

Infections

Metabolic disturbances

NAC

Nutritional deficiency

Renal failure

*Monitor ICP, CPP & cerebral oxygenation *Elevate head end to 30° *Monitor fluid status *3% NS *Avoid NGT and suction

*Platelet count & coagulation profile (12th hourly) *Inj. Vit. K *Cryoprecipitate

*Discontinue medications *Avoid nephrotoxic & hepatotoxic drugs

*Ranitidine *PPI's

Monitor CVP w/ central venous catheter

Frequent monitoring of mental status

*CBC (12th hourly) *CXR; sputum, blood & urine cultures (daily) *Cefotaxime, meropenem, fluconazole or vancomycin

*Serum BCH, ABG, lactate (12th hourly) *Serum glucose (2nd hourly)

NAC (IV × 2d then P.O.)

*Eternal feeding *Parental feeding

Urinary I/O

Etiology Specific Management

Etiology specific management

*H/o acetaminophen intake *Suspected if no H/o but elevated aminotransferase (>3500 IU/L)

*Jaundice, coagulopathy, thrombocytopenia ± hypoglycemia *Hypertension & proteinuria *+ Steatosis during liver imaging or biopsy

*Elevated aminotransferase responding to fluid resuscitation *Associated renal dysfunction & muscle necrosis

*+ Serum autoantibodies *+ Liver biopsy

*Abdominal pain, ascites and hepatomegaly *+ Liver imaging (CT/MRV/venogram/doppler USG)

*H/o hepatotoxic drug intake (<6m) *Unlikely if H/o intake >1 or 2 years

*Massive hepatomegaly *+ Liver imaging & biopsy

*H/o mushroom intake *Suspected if no H/o but severe GI Sx (NVD)

*+ Hepatitis serology *+ Liver biopsy for HSV

Serum bilirubin >20g/dL, bilirubin:alkaline phosphatase >2.0, low serum ceruloplasmin, elevated serum & urine copper, + KF ring, + liver biopsy

Etiology undetermined

Acetaminophen toxicity

Acute fatty liver of pregnancy/HELLP

Acute ischemic injury

Autoimmune

Budd-Chiari

Drug induced

Malignant infiltration

Mushroom poisoning

Viral

Wilson's disease

Intermediate etiology

*Activated charcoal *NAC

Deliver immediately

Manage the cause of ischemia

*Prednisolone *Transplantation

Transplantation

Discontinue all possible medications except essential drugs

Supportive Rx

*Activated charcoal & gastric lavage *Penicillin G or Silibinin *Fluid resuscitation

*Supportive Rx *Lamivudine or adefovir *Acyclovir

*Dialysis or hemofiltration or plasmapheresis or plasma exchange *Transplantation

*Incomplete drug or toxin intake H/o *Transjugular biopsy to R/o mailgnancy, Wilson's disease, autoimmune hepatitis or viral hepatitis

Complication Specific Management

Complication specific management

Ascites

Cerebral edema & increased ICP

Coagulopathy

Hemodynamic instability

Hepatic encephalopathy

Metabolic disturbances

Renal failure

*Therapeutic paracentesis w/ 25% albumin *<3 mEq/kg of Na daily *Lasix & aldactone

ICP >25 mmHg

+ Bleeding or prior to surgery

*Colloid, dextrose in crystalloid (if hypoglycemic) & 1/2 NS w/ 75 mg/L HCO3 (if acidotic) *Norepinephrine ± vasopressin *Hydrocortisone

Grade

Rx acidosis, alkalosis, hypophosphatemia, hypomagnesemia, hypokalemia or hypoglycemia accordingly

*Urinary catheterization *Continuous venovenous hemodialysis

SjO2

*Platelet transfusion (if ≤50,000/mm2) *FFP /+ rFVIIa (if INR≥1.5)

I

II

III/IV

<80

>80

2nd hourly monitoring in quiet environment in high dependency ward

*ICU management *Stat CT to R/O ICH *Short acting BZD *Lactulose

ICU management *Intubation & mechanical ventilation *Propofol *Elevate head end to 30° *Quiet environment monitoring for CVP, hemodynamic & renal parameters, serum electrolytes, acid base status & neurological status

20% mannitol

No improvement

Hyperventillation

Worsening

3% NS

Transfer to ICU

Reduce core temperature to 32°-34° (monitor for arrhythmias)

Thiopental 125 mg IV bolus

Improvement or refractory

Transplantation

Do's

General Management

• Transplant center:
  • Place patient immediately on the transplant list if progression of 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
• To prevent cerebral edema and increased ICP:
  • Administer 3% NS at 0.1-1 ml/kg/hr IV infusion
  • Maintain serum sodium between 145-155 mEq/dL and hold if serum osmolality is >360 mOsm/L
• To prevent coagulopathy:
  • Administer 5-10 mg of Inj. vitamin K SC
  • Administer cryoprecipitate if serum fibrinogen <100 mg/dL
  • Maintain platelet count around 20,000/mm3
• Avoid drugs:
  • Especially aminoglycosides
• Prophylactic antibiotics
  • Cefotaxime: 100-200 mg/kg/day IV; every 6-8 hours/ If allergic to penicillin, meropenem: 20-40 mg/kg IV; every 8 hours/ Flucanazole: 3-12 mg/kg IV; daily/ In case of catheter related sepsis and suspected MRSA, vancomycin: 40 mg/kg/day IV; every 6-8 hours
  • Administer 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 prevent nutritional deficiency:
  • 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 administer protein if ammonia >200 mcg/dL.
• 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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