Article Text

PDF
005
REDUCING ADVERSE EFFECTS FROM INTRAVENOUS N-ACETYLECYSTEINE TREATMENT OF PARACETOMOL POISONING: PRINCIPAL RESULTS OF THE SCOTTISH AND NEWCASTLE ANTEMETIC ORE_TREATMENT FOR PARACETAMOL POISONING (SNAP) RANDOMISED CONTROLLED TRIAL
  1. A Gray1,4,
  2. J Dear5,4,
  3. R Thanacoody7,
  4. S Thomas7,
  5. M Eddleston5,4,
  6. E Sandilands5,
  7. J Coyle1,
  8. J Cooper6,
  9. A Rodriguez2,
  10. I Butcher2,
  11. S Lewis3,
  12. A Vliegenthart4,
  13. A Veiraiah5,
  14. D Webb4,
  15. N Bateman5
  1. 1Department of Emergency Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
  2. 2Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, United Kingdom
  3. 3Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom
  4. 4University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
  5. 5National Poisons Information Service, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
  6. 6Department of Emergency Medicine, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
  7. 7Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom

Abstract

Objectives & Background Paracetamol poisoning is common worldwide. Standard intravenous N-acetylcysteine (NAC) therapy is complex, and commonly associated with concentration-related adverse effects and the potential for administration errors. We aimed to determine whether adverse effect incidence could be reduced by antiemetic pre-treatment and/or a simpler and shorter intravenous N-acetylcysteine regimen.

Methods We delivered, in 3 centres, a randomised factorial trial comparing a modified 12 h (100 mg/kg over 2 h, 200 mg/kg over 10 h) with a standard 20.25 h NAC regimen (150 mg/kg 15 min, 50 mg/kg 4 h, 100 mg/kg 16 h) with and without pre-treatment with ondansetron (4 mg IV). The primary endpoint was absence of retching, vomiting or need for rescue antiemetic at 2 h; secondary endpoints included the incidence of anaphylactoid reactions, the need for medication or treatment interruption, and hepatic toxicity (ALT, INR).

Results In 217 participants, retching and vomiting were less common with ondansetron than placebo (OR 0.406, 97.5% CI 0.205–0.803, p=0.0031) and with the modified compared to the conventional acetylcysteine regimen (OR 0.260, 97.5% CI 0.130–0.518, p<0.0001). Frequency of anaphylactoid reactions was not affected by ondansetron, but less common with modified acetylcysteine; severe reactions 5/108 (4.6%) vs. 31/100 (31%) (p<0.0001). The proportion of patients with a 50% increase in ALT was not significantly different comparing conventional with modified regimens (OR 0.603, 97.5% CI 0.199–1.831), but more common with ondansetron than placebo (OR 3.295, 97.5% CI 1.013–10.723, p=0.0235).

Conclusion In patients with paracetamol poisoning requiring acetylcysteine, adverse effects were substantially reduced by ondansetron pre-treatment and by using a modified, shorter treatment regimen. Ondansetron, but not the modified regimen, increased the frequency of liver function abnormalities. If large effectiveness studies confirm the modified regimen is non-inferior to conventional then shorter and safer treatment would be possible for this common poisoning.

  • emergency care systems
  • emergency care systems
  • emergency care systems
  • emergency care systems
  • emergency care systems
  • emergency care systems

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.