N-acetyle cysteine (Parvolex)

see also:

• paracetamol overdose

• MJA 2019 guidelines - WH intranet only
• MJA 2019 guideline summary - WH intranet only
• appears to result in much lower incidences of anaphylactoid reactions than the 3 bag regime (2% vs 8%) ⁴⁾
• all potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine.
• 200 mg/kg (max. 22g) in 500mL (child 7mL/kg to max 500mL) 5% dextrose or 0.9% saline given IV over 4 hours, then
• 100 mg/kg (max. 11g) in 1000mL (child 14mL/kg to max 1000mL) 5% dextrose or 0.9% saline given IV given over 16 hours, OR, if “increased NAC dose indicated” then use 200mg/kg over 16hrs instead:
  • increased NAC dose indications:
    • massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line
    • patients ingesting ≥ 30 g or ≥ 500 mg/kg
    • NB. contact Poisons Info for further advice if either:
      • modified release paracetamol overdoses of > 50g or 1g/kg
      • paracetamol concentration more than triple the nomogram line
      • serial paracetamol concentrations remain unchanged or increasing
      • ALT > 1000 U/L
      • neonatal paracetamol poisonings
• ALT and paracetamol concentration are required in ALL patients before ceasing acetylcysteine infusion.
  • Continue acetylcysteine treatment at the rate of the second infusion if:
    • Paracetamol concentration > 10 mg/L (66 μmol/L), OR
    • ALT > 50 U/L and increasing (if baseline ALT > 50 U/L) BUT small fluctuations in ALT (e.g. +/- 20 U/L or +/-10%) are common and do not on their own indicate the need for ongoing acetylcysteine.
  • Cease the ongoing infusion if ALL of the following apply:
    • ALT or AST are decreasing
    • INR < 2.0
    • Patient clinically well
    • for modified-release ingestions and those with an initial paracetamol concentration greater than double the nomogram line, paracetamol concentration has fallen below 10 mg/L (66 μmol/L)
• Patients should be advised if they develop abdominal pain, nausea or vomiting further assessment is required.
• Consult the Liver Transplant Unit (or your local gastroenterology unit) if ANY of:
  • INR > 3.0 at 48 hours or > 4.5 at any time
  • oliguria or creatinine > 200 μmol/L,
  • persistent acidosis (pH < 7.3) or arterial lactate > 3 mmol/L
  • systolic hypotension with BP < 80mmHg, despite resuscitation
  • hypoglycaemia, severe thrombocytopenia or encephalopathy of any degree,
  • or any alteration of consciousness (GCS < 15) not associated with sedative co-ingestions.
• DO NOT GIVE clotting factors unless bleeding or after discussion with a Liver Transplant Unit

• may cause nausea and vomiting but if given with anti-emetics and tolerated, appears to be as effective as iv NAC
• unfortunately substantial number of paracetamol overdose patients are already vomiting, have decreased GCS from-co-ingestants, unable to swallow oral meds, or are non-compliant, thus most centres opt for iv NAC.

• dose should be based on actual body weight not lean body weight as previously used, and maximum weight for calculations is 110kg
• MJA 2015 NAC infusion guidelines for adults is for 3 infusions over a 21 hour period:
  • 150mg/kg in 200ml 5% dextrose IV over 15mins (usually 60min),
    • BUT this is usually given over 1 hour to minimise anaphylactoid reactions, then,
  • 50mg/kg in 500ml 5% dextrose IV over 4 hours, then,
  • 100mg/kg in 1000ml 5% dextrose IV over 16 hours (consider doubling this dose to 200mg/kg if paracetamol concentration more than double the nomogram line)
  • acetylcysteine should be continued longer if the ALT level is increasing (greater than50 U/L) or the paracetamol concentration is greater than 10 mg/L (66 μmol/L)
• MJA 2015 guidelines for children:
  • weight < 20kg:
    • 150mg/kg NAC in 3ml/kg 5% dextrose over 15min (usually 60min)
    • then 50mg/kg NAC in 7ml/kg 5% dextrose over 4hrs
    • then 50mg/kg NAC in 7ml/kg 5% dextrose over 8hrs
    • then 50mg/kg NAC in 7ml/kg 5% dextrose over 8hrs
  • weight > 20kg:
    • 150mg/kg NAC in 100ml 5% dextrose over 15min (usually 60min)
    • then 50mg/kg NAC in 250ml 5% dextrose over 4hrs
    • then 50mg/kg NAC in 250ml 5% dextrose over 8hrs
    • then 50mg/kg NAC in 250ml 5% dextrose over 8hrs