Article Text


Oral or intravenous antidote for paracetamol overdose
  1. Simon Clarke, Specialist Registrar,
  2. Katrina Herren, Research Fellow
  1. Department of Emergency Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK;
  1. kevin.mackway-jones{at}


A short cut review was carried out to establish whether there was any evidence to decide between oral or intravenous antidote in paracetamol (acetaminophen) poisoning. Altogether 330 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

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Report by Simon Clarke,Specialist RegistrarChecked by Katrina Herren, Research Fellow

Clinical scenario

A 23 year old woman attends an emergency department having taken sixty 500 mg paracetamol tablets. Her four hour paracetamol levels are above the treatment line. She does not want to be treated with intravenous therapy. You wonder whether oral antidote is as effective.

Three part question

In [patients who need an antidote for paracetamol overdose] is [intravenous therapy better than oral therapy] at [preventing liver damage and death]?

Search strategy

Medline 1966 to 12/01 using the OVID interface. [exp acetylcysteine OR OR OR exp methionine/ OR OR exp antidote OR] AND [exp overdose/ OR overdos$.mp OR exp poisons OR poison$.mp OR acute intoxic$.mp OR acute toxic$.mp] AND [exp acetamoniphen OR OR exp paracetamol OR OR (co-codamol OR co-dydramol OR co-proxamol).mp] LIMIT to human AND English language.

Search outcome

Altogether 330 papers were identified, of which two were directly relevant to the question (table 1).

Table 1


Perry's study used historical controls although the demographic characteristics of the two groups were remarkably similar. It was not included in Buckley's meta-analysis because the patients were not recruited sequentially and it was unclear whether the patients were treated solely at the study centre (possible variations in other treatment modalities could act as confounding factors).

There have been no RCTs in this area. A meta-analysis of observational studies has failed to show a difference in efficacy between the oral and intravenous routes. However, these studies do not address other factors that may influence the choice of route, which include: activated charcoal adsorbs antidote and therefore precludes its use; the IV regimen is shorter than the oral (24 hours and 52 hours respectively); the IV route is safer with patients with altered levels of consciousness (for example due to coingestants) who may subsequently lose their airway protective reflexes.


The IV route is the treatment of choice for paracetamol poisoning, but the oral route has a similar efficacy and is a suitable alternative if IV access is difficult (for example IV drug abusers) or refused by the patient.

Report by Simon Clarke,Specialist RegistrarChecked by Katrina Herren, Research Fellow


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