›In vitro data showing NAC partially prevents glutathione depletion
›Animal models showing reduced hepatocellular necrosis
›No controlled human trials; empiric use recommended given mechanism
›IV NAC protocol
›Loading dose
›150 mg/kg IV in 200 mL D5W over 60 minutes
›Second infusion
›50 mg/kg IV in 500 mL D5W over 4 hours
›Third infusion
›100 mg/kg IV in 1000 mL D5W over 16 hours
›Continue until hepatic injury resolves or stabilizes
›Anaphylactoid reactions
›Occur in up to 15% of IV NAC administration
›Stop infusion and treat with antihistamine and corticosteroid
›Resume at slower rate when reaction resolves
Supportive care and hemodynamic management
›Fluid resuscitation
›Balanced crystalloid preferred
›Lactated Ringer's or Plasma-Lyte
›Normal saline avoidance in metabolic acidosis
›Cautious approach in pulmonary edema
›Avoid fluid overload in ARDS pattern
›Target CVP and urine output guided
›Vasopressor therapy
›Norepinephrine as first line vasopressor
›Starting dose 0.1 to 0.2 mcg/kg/minute
›Titrate to MAP >= 65 mmHg
›Maximum 1 to 2 mcg/kg/minute before adding second agent
›Vasopressin as second agent
›0.03 to 0.04 units/minute fixed dose
›Added for norepinephrine-refractory shock
›Avoid phenylephrine
›Potentiates EDB nephrotoxicity in animal models
›Class of evidence: animal model data
›Metabolic acidosis management
›Sodium bicarbonate
›pH < 7.10 with cardiovascular instability
›1 to 2 mEq/kg IV as bolus
›Risk of hypernatremia and fluid overload
›Renal replacement therapy
›CRRT preferred in hemodynamic instability
›Correction of refractory acidosis and volume overload
Hepatic failure management
›Hepatic support measures
›Glucose supplementation
›10% dextrose infusion for hypoglycemia prevention
›Target glucose 5 to 10 mmol/l
›Hourly glucose monitoring in fulminant failure
›Coagulopathy management
›Fresh frozen plasma for active bleeding or procedures
›Vitamin K 10 mg IV once
›Avoid prophylactic FFP as it masks coagulopathy severity
›Hepatic encephalopathy
›Lactulose 15 to 30 mL every 4 to 6 hours titrated to 2 to 3 soft stools per day
›Rifaximin 550 mg PO twice daily if tolerated
›Low ammonia generating protein restriction short term
›Liver transplant consideration
›Early referral to transplant center in fulminant hepatic failure
›Contact transplant hepatology within 24 hours
›King's College criteria adapted assessment
›Contraindications to transplant
›Ongoing suicidal intent without psychiatric support
›Multisystem failure with poor expected outcome
›AKI management
›Nephrotoxic medication avoidance
›NSAIDs contraindicated
›ACE inhibitors and ARBs held
›Aminoglycosides avoided
›Drug dosing adjustment
›Creatinine-based dosing adjustments
›Pharmacist consultation for critical medications
›Renal replacement therapy initiation criteria
›Refractory hyperkalemia (K+ > 6.5 mmol/l)
›Refractory metabolic acidosis
›Fluid overload with pulmonary edema
›BUN > 35 mmol/l with uremic symptoms
›Contraindicated and cautioned medications
›CYP2E1 inducers
›Avoid isoniazid during acute poisoning management
›Ethanol potentiates toxic metabolite formation
›Aldehyde dehydrogenase inhibitors
›Disulfiram significantly increases EDB toxicity
›Cyanamide similarly contraindicated
›Alpha-adrenergic agonists
›Phenylephrine potentiates nephrotoxicity
›Use norepinephrine instead for vasopressor support
›Hepatotoxic drugs
›Avoid statins, azole antifungals, amiodarone acutely
›Review all medications for hepatic metabolism burden