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

Lookup NU author(s): Dr Harry Thanacoody, Professor Simon Thomas

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Abstract

Background: Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. An effective antidote, acetylcysteine (NAC) was introduced in the 1970s and the intravenous (IV) regimen introduced at that time has continued effectively unchanged since. This antidotal therapy involves three different infusion regimens (dose and time) of antidote and lasts over 20 hours. The same weight-related dose of NAC is used in all patients irrespective of paracetamol dose. Recognised complications include a high incidence of nausea and vomiting, anaphylactoid reactions and dosing errors. A simpler, shorter regimen has the potential to improve patient safety and reduce hospital length of stay. We therefore designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard and modified regimens of NAC. Methods/Design: We designed a double blind clinical trial using a 2 x 2 factorial design involving four parallel groups. Here, we compared pre-treatment with ondansetron 4 mg intravenously against placebo on nausea and vomiting following the standard (20.25 hour) regimen of NAC, or a novel 12 h regimen, in patients with paracetamol poisoning. Each regimen delivered a total dose of 300 mg/kg bodyweight NAC. Patients were stratified on paracetamol dose, perceived risk factors, and time to presentation, and randomisation performed to balance entry into the four trial groups. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions was documented, and end of treatment liver function assessed. Where clinically necessary, further doses of NAC were administered as per standard UK protocols at the end of the first antidote course. Discussion: This study is the first attempt to formally examine new methods of administering IV NAC in patients with paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new regimen. In addition since the rate of an anaphylactoid response appears to relate to plasma concentration of both NAC and paracetamol anaphylactoid reactions should also be less likely. This study is not powered to assess the relative efficacy of the modified regimen compared to standard treatment, however it will give useful information upon which 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 who have ingested overdoses of paracetamol, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk.


Publication metadata

Author(s): Thanacoody HKR, Gray A, Dear JW, Coyle J, Sandilands EA, Webb DJ, Lewis S, Eddleston M, Thomas SHL, Bateman DN

Publication type: Article

Publication status: Published

Journal: BMC Pharmacology and Toxicology

Year: 2013

Volume: 14

Issue: 1

Pages: 20

Print publication date: 04/04/2013

Date deposited: 15/04/2013

ISSN (electronic): 1471-2210

Publisher: BioMed Central Ltd.

URL: http://dx.doi.org/10.1186/2050-6511-14-20

DOI: 10.1186/2050-6511-14-20


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