Toxin:: [[Paracetamol overdose]] see: [Goldfrank - N-Acetylcysteine](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=518) and [Murray N-acetylcysteine](x-devonthink-item://DA1896AC-D57C-4A67-B2C7-65B1D27BB53E?page=444) # When to use - paracetamol - mushrooms (amanita phalloides aka [[Death Cap mushroom]]) - etc?? - "NAC is indicated for its antioxidant properties for use in poisonings by a variety of other agents, including paraquat, acrylonitrile, cyclophosphamide, amanita mushrooms and hydrocarbons including carbon tetrachloride, chloroform and essential oils" # mechanism of action - prodrug to L-cystine, sulfydryl group donor → restores hepatic *glutathione levels* to reduce NAPQI levels - reduction of NAPQI back to paracetamol - directly bind NAPQI (glutathione substrate) - increase sulfation - anti-inflammatory effect on liver (unclear mechanism) for fulminant liver disease and prevents further injury from murray: 1. increased glutathione availability 2. direct binding to NAPQI 3. provision of inorganic sulfate 4. reduction of NAPQI back to paracetamol. "The antioxidant properties of NAC may offer benefit in a number of other poisonings in which oxidative stress is an important toxic mechanism and may also explain its beneficial effects in liver failure of any cause." # When to start? - paracetamol level over nomogram - \> 8 hours have already passed and suspected # Dose 2 bag regimen used essentially universally in Australia (decreases anaphylactoid reactions, but not clearly superior to three-bag regimen): - 200mg/kg (to 110kg) in 1000mL 5% dextrose over 4 hours - 100mg/kg in 1L dextrose over 16 hours (*double to 200mg/kg* if massive ingestion > double dose of second bag of NAC if massive overdose (2x nomogram or >30g); d/w toxicologist if dose >50g ## Extended NAC infusion see: [Austin Tox - Extended NAC](x-devonthink-item://474B0403-CD47-41DD-9058-2A361A341DF4) **Indications for extended treatment with NAC:** Following initial 20-hour NAC infusion: - ALT >50 AND rising - APAP concentration detectable AND \> 10 mg/L (> 66 umol) **Indications for discontinuation of NAC (ALL criteria must be met)** - ALT or AST concentration decreasing - INR < 2 - Patient clinically well - APAP concentration <10mg/L (< 66 umol/L) # Special considerations **Pregnancy:** NAC crosses the placenta. When indicated, it is beneficial for both mother and fetus. **Paediatric:** the dose of NAC is the same as for adults. However, it should be infused in smaller volumes of 5% glucose (use 0.45% sodium chloride with 5% glucose if there are concerns about development of hyponatraemia). *Children <20 kg body weight:* - 200 mg/kg NAC (1 mL/kg of 200 mg/mL NAC solution) in 100 mL 5% glucose IV over 4 hours followed by - 100 mg/kg NAC (0.5 mL/kg of 200 mg/mL NAC solution) in 250 mL 5% glucose over 16 hours. *Children 20–50 kg body weight:* - 200 mg/kg NAC (1 mL/kg of 200 mg/mL NAC solution) in 250 mL 5% glucose IV over 4 hours followed by - 100 mg/kg NAC (1 mL/kg of 200 mg/mL NAC solution) in 500 mL 5% glucose IV over 16 hours. # Endpoint can stop tx when: - ALT < 50 u/L - paracetamol <10mg/L stopped earlier if the risk of hepatotoxicity is excluded. NAC should be continued beyond 20 hours in patients if paracetamol remains detectable at the end of the infusion or if there is biochemical evidence of hepatotoxicity. > Repeat the final dose of 100 mg/kg NAC in 1000 mL of 5% glucose IV over 16 hours until paracetamol is undetectable, transaminases stabilise or improve and the patient is clinically well. # side effects - [[anaphylactoid]] reaction (~10% of patients) - rarely progresses to anaphylaxis; does not routinely require adrenaline - temporarily pause infusion, give antihistamines, IVF, bronchodilators as needed - infusion may be **restarted** when symptoms improved