Open Access Study protocol

Scottish and Newcastle Antiemetic Pre-treatment for paracetamol poisoning study (SNAP)

H K Ruben Thanacoody1, Alasdair Gray2, James W Dear34, Judy Coyle2, Euan A Sandilands4, David J Webb3, Steff Lewis5, Michael Eddleston34, Simon HL Thomas1 and D Nicholas Bateman4*

Author Affiliations

1 Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne, & Royal Victoria Infirmary, Newcastle upon Tyne, UK

2 Emergency Department, Royal Infirmary of Edinburgh, Edinburgh, UK

3 University/BHF Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK

4 NPIS Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK

5 Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK

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BMC Pharmacology and Toxicology 2013, 14:20  doi:10.1186/2050-6511-14-20

Published: 4 April 2013



Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen.


We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course.


This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk.

Trial registration

EudraCT number 2009-017800-10, IdentifierNCT01050270

Paracetamol; Acetylcysteine; Overdose; Antidotes; Hepatotoxicity