›Duration extended to 6 days if clinical response inadequate
›Mechanism
›Blocks hepatic uptake of alpha-amanitin via membrane transporter inhibition
›Free radical scavenging activity
›Hepatoprotective through multiple pathways
›Access in the US
›Not FDA-approved for routine use in the US
›Available via emergency IND from FDA — contact Poison Control immediately
›Survival rate approximately 90% with silibinin vs. 59% with supportive care alone
›Evidence level
›ACG Acute Liver Failure Guidelines — first-line recommendation
›Class IIa recommendation based on large case series
›IV Penicillin G — second-line or combination therapy
›Dosing
›Day 1: 1,000,000 IU/kg IV as continuous infusion
›Days 2-3: 1,500,000 IU/kg/day IV as continuous infusion
›Mechanism
›Blocks hepatic uptake of alpha-amanitin via OATP transporter inhibition
›Reduces hepatocellular toxin loading
›Evidence
›Combined penicillin plus silibinin protocol: only 1.5% treatment failure
›Silibinin alone: 41.7% treatment failure in one large series
›Contraindicated in documented penicillin allergy; use silibinin alone
›IV N-Acetylcysteine (NAC) — adjunctive therapy
›Dosing protocol
›150 mg/kg IV over 15 minutes loading dose
›Then 50 mg/kg IV over 4 hours
›Then 100 mg/kg IV over 16 hours
›Continue beyond standard protocol based on clinical response
›Mechanism
›Glutathione replenishment and free radical scavenging
›Hepatoprotective in ALF from multiple etiologies
›Adverse effects
›Anaphylactoid reaction incidence approximately 5%
›Slow infusion rate or premedicate with antihistamine if reaction occurs
›Evidence
›Class IIa recommendation for ALF of non-acetaminophen etiology
›Systematic review supports use in amatoxin poisoning
ICU supportive management
›Hepatic encephalopathy management
›Lactulose (if enteral access)
›25-30 mL PO/NG q4-6h; titrate to 3-4 soft stools per day
›Reduces ammonia production
›Rifaximin
›550 mg PO/NG BID as adjunctive bowel decontamination
›Intracranial pressure monitoring (Grade III-IV encephalopathy)
›Consider epidural or subdural ICP monitor
›Target ICP <20-25 mmHg, CPP >60 mmHg
›Head of bed elevation 30 degrees
›Minimize agitation and stimulation
›Coagulopathy management
›Do NOT correct INR prophylactically
›INR is a critical prognostic marker; normalization obscures trajectory
›Reserve FFP for active bleeding only
›FFP 10-15 mL/kg IV for active hemorrhage
›Target fibrinogen >1.5 g/L with cryoprecipitate if depleted
›Vitamin K 10 mg IV daily
›Correct if deficiency component present
›Platelet transfusion for platelet count <50 x10^9/L with active bleeding
›Hypoglycemia management
›Continuous glucose monitoring
›Blood glucose q1-4h
›IV dextrose 10% infusion for persistent hypoglycemia
›Target glucose 4-8 mmol/L
›IV dextrose 50% 50 mL bolus for acute hypoglycemia <2.5 mmol/L
›Renal replacement therapy
›Indications for hemodialysis or CRRT
›AKI with creatinine >350 mmol/L or oliguria unresponsive to fluids
›Severe electrolyte disturbances
›Metabolic acidosis pH <7.2 unresponsive to treatment
›Hemoperfusion and plasmapheresis
›Limited benefit for toxin removal (amatoxins rapidly absorbed and renally excreted)
›Plasmapheresis may serve as bridge to transplant for coagulopathy management
›Indications
›Irreversible acute liver failure meeting transplant criteria
›Ganzert criteria: creatinine >106 mmol/L and PT >100 seconds days 3-10
›Escudie criteria: prothrombin index <25% with creatinine >106 mmol/L from day 3
›King's College: INR >6.5 or any 3 unfavorable criteria
›Timing imperative
›Early listing — do not wait for encephalopathy
›Survival rates significantly better with early transplantation
›Contraindications to transplantation
›Severe sepsis or multi-organ failure precluding surgery
›Active uncontrolled infection
›Hemodynamic instability requiring high-dose vasopressors
›Malignancy or other terminal illness
›Post-transplant management considerations
›Standard calcineurin inhibitor immunosuppression
›Tacrolimus or cyclosporine-based protocol
›Long-term outcome
›Excellent 1-year survival post-transplant for amatoxin ALF
›Hepatotoxic medications — discontinue or avoid
›Acetaminophen — absolute contraindication
›Any dose adds hepatotoxic burden
›Statins
›Myopathy and hepatotoxicity risk
›NSAIDs
›Renal impairment and antiplatelet effects
›Antibiotics with hepatic metabolism
›Tetracyclines, macrolides — use alternatives when needed