Methods
In approaching this topic, a search of PubMed was done using index terms: paracetamol; acetylcysteine; dose; toxicity; massive paracetamol overdose.
Of the many thousand references identified the author has manually chosen those that specifically deal with the areas to be covered in this discussion and identified references also using a large personal collection that are relevant.
A focus on the 3 areas most apposite to the issue of increasing doses of NAC in large paracetamol overdose has been adopted, these being evidence that:-
  1. larger doses of paracetamol cause increased toxicity even with NAC therapy
  2. increasing NAC dose may have efficacy in large paracetamol overdoses
  3. the various modes of action suggested for NAC that may be relevant to any increased efficacy from a larger NAC dose.