BET 1: In paracetamol overdose, is oral N-acetylcysteine as effective as intravenous N-acetylcysteine?

Correspondence to Dr Bernard A Foex, University of Manchester and Manchester Royal Infirmary, Manchester M13 9WL, UK; [email protected]

Three-part question

In (patients who need treatment for paracetamol poisoning), is (oral N-acetylcysteine (NAC) as safe and effective as intravenous NAC) at (preventing liver damage and death)?

Clinical scenario

A 17-year-old woman has presented to the ED after taking forty 500 mg tablets of paracetamol. Her 4-hour plasma paracetamol levels are above the treatment line. However, she is needle-phobic and refusing intravenous treatment. You want to treat her with an oral antidote and wonder if oral NAC is as effective as intravenous.

Search strategy

Medline via OVID interface searched to week 2 February 2018.

[exp acetaminophen OR acetaminophen.mp OR paracetamol.mp OR paracetamol$.mp] AND [exp poisoning OR poisoning.mp OR poison$.mp OR overdose.mp OR overdose$.mp] AND [exp. Acetylcysteine OR acetylcytseine.mp OR N-acetylcysteine.mp OR parvolex.mp OR antidote.mp] LIMIT human AND english language

Cochrane Database of Systematic Reviews searched to week 2 February 2018.

[paracetamol.mp] AND [Overdose.mp] AND [N-acetylcycsteine.mp]

Search outcome

Medline: 746 papers were identified. There were two systematic reviews and one comparative study published after the most recent review. Three other studies were included for further relevant information.

Cochrane Database: Three papers were identified, of which one was relevant. It was also identified by the Medline search.

One additional systematic review did not appear on Medline but was found through the Wikipedia entry for acetylcysteine.

Data from the studies are shown in table 1.

Table 1

In paracetamol overdose, is oral N-acetylcysteine as effective as intravenous N-acetylcysteine?

Author, year and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study weaknesses
Buckley et al,4 1999, USA	An observational study: 981 patients who presented with paracetamol overdose, 205 of whom required treatment with NAC which was given intravenously. Meta-analysis: systematic search of Medline up to December 1998. No randomised trials were identified. Seven case series were included (four presented data on patients treated with intravenous NAC and three presented data on patients treated with oral NAC).	Observational study and a meta-analysis.	Hepatotoxicity (transaminase >1000 IU/L)/L.	279/1462 (19%) of patients treated with oral NAC vs 60/341 (17.5%) of patients treated with intravenous NAC.	Guidelines on the management of paracetamol overdose have since been changed. Variations in the...