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Timing of antidote in paracetamol overdose

Three Part Question

In [patients with paracetamol overdose] does [the early use of n-acetyl cysteine rather than delaying until levels are known] reduce [mortality and hepatotoxicity]

Clinical Scenario

A patient arrives in the emergency department claiming to have taken 100 paracetamol about an hour ago. Concerned that the dosage taken is quite high you wonder whether it would be better to start acetyl cysteine now rather than wait the three hours to check levels.

Search Strategy

Medline 1966-4/week 4 05 using the OVID interface
[{exp Acetaminophen OR OR} AND {exp poisoning/ or exp overdose/ or exp suicide/ or exp suicide, attempted/ or poiso$.af. or parasuicid$.mp. or para-suicid$.mp. or overdos$.af. or suicid$.af. or (deliberate adj5 self adj5 harm).af. or} AND {exp Acetylcysteine OR acetyl OR OR OR}]LIMIT to human AND English Language

Search Outcome

332 papers found none of which directly addressed the three part question.


No papers address the issue of whether starting acetylcysteine within 4 hours of overdose is beneficial, the only evidence shows that before 10 hours is better than after. Other studies have shown that levels are frequently below that expected from the stated overdose and acetylcysteine is not without risk. It should also be considered that if 4 hours are required for sufficient absorption to assess peak levels one would expect that glutathione depletion and subsequent liver damage may take longer still.

Clinical Bottom Line

No evidence suggests acetylcysteine should be started before levels are known and therefore local guidelines should be followed.