Should ondanestron be used as the first-line anti-emetic in paracetamol overdose

Date First Published:
January 25, 2008
Last Updated:
January 25, 2008
Report by:
Emma Jenkinson,, Foundation Year One (City Hospital, Birmingham, UK)
Search checked by:
Nigel Langford,, City Hospital, Birmingham, UK
Three-Part Question:
In [a patient with nausea and vomiting after paracetamol intoxication] is [ondansetron better than other anti-emetics] at [reducing the incidence of vomiting]?
Clinical Scenario:
A 19-year-old girl attends the emergency department six hours after ingesting 80 paracetamol tablets. Her serum paracetamol level is above the treatment line and acetylcysteine is administered intravenously. She experiences nausea and vomiting. You have heard that ondansetron is more effective than other anti-emetics in this patient group and wonder whether this should be your first-line option.
Search Strategy:
Medline 1950 to August week 5 2007 (OVID interface)
The Cochrane Library Issue 3 2007
Search Details:
Medline: (ondansetron.mp or exp Ondansetron/) AND (paracetamol.mp or exp Acetaminophen/), 20 records.

Cochrane: ondanstron (ti, ab.kw.) AND paracetamol (ti, ab.kw.)—nine records; ondansetron (ti, ab.kw.) AND acetaminophen (ti, ab.kw.)—11 records.
Outcome:
None of the papers identified in the Cochrane search were relevant. Four of the articles identified using Medline were relevant
Relevant Paper(s):
Study Title Patient Group Study type (level of evidence) Outcomes Key results Study Weaknesses
The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning. Clark RF, Chen R, Williams SR, et al. 1996, USA 6 Patients (18–65 years) with nausea and at least one episode of vomit after laboratory confirmed paracetamol overdose
Ingested doses/paracetamol levels not specified.
8 mg ondansetron IV administered (single dose).		 Prospective observational study (single arm) Reduction in nausea (as perceived by patient) All patients reported a reduction in nausea after ondansetron. No patient vomited after ondansetron Small patient numbers. Single arm with no control. Reliant on subjective patient reports therefore subject to bias
Study supported by drug company research grant
Ondansetron for treating nausea and vomiting in the poisoned patient. Reed MD, Marx CM. 1994, USA 2 Patients with overdose: 13-year-old with ingestion of unknown amount paracetamol, levels at 12.5 hours 82.6 mg/l Case report Successful anti-emesis Effective anti-emesis with ondansetron after chlorpromazine had failed Isolated case report
Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions. Scharman EJ. 1998, USA 78 Patients with laboratory-verified paracetamol toxicity and vomiting (25 with and 53 without coningestant). Patient ages ranged from 13 to 50 years (mean 21.5)
Range of paracetamol levels not specified
Four patients received 0.15 mg/kg ondansetron, dose not specified for other patients		 Retrospective study Successful anti-emesis 33.3% given non-ondansetron anti-emetic failed therapy, 16.7% given ondansetron failed therapy<br><br>Of those with isolated paracetamol overdose, 59.6% given non-ondansetron anti-emetic failed therapy and 12.5% given ondansetron failed therapy<br><br>Concluded that ondansetron should be second-line therapy Retrospective No randomisation. Large number of uncontrolled variables
No attempt to determine statistical significance of results
Author states that ondansetron has lower failure rate than other anti-emetics but do not indicate the statistical significance of this difference. High-dose ondansetron administered (where stated)
Ondansetron to prevent emesis following N-acetylcysteine for acetaminophen intoxication. Tobias JD, Gregory DF, Deshpande JK. 1992, USA 1 17-year-old with paracetamol overdose 300 mg/kg ingested.
Ondansetron 0.15 mg/kg IV TDS (total 3 doses)		 Case report Successful anti-emesis Successful anti-emesis after single dose Isolated case report
Author Commentary:
All four articles report that ondansetron is an effective anti-emetic in patients with vomiting after paracetamol overdose. Two of these are isolated case reports( Reed, Tobias) Another is a single-arm study involving only small numbers of patients (Clark)

A larger study attempts to compare ondansetron against other anti-emetics (Scharman). The methodology is insufficiently robust to allow direct comparison in the table. The author concludes, however, that ondansetron should be used as a second rather than a first-line therapy because of cost implications. (The current costs of single intravenous ampoules for anti-emetics in the United Kingdom are as follows: cyclizine 50 mg £0.54, metoclopramide 10 mg £0.26 and ondansetron 4 mg £5.99. (BNF).

Furthermore, it is not clear what dose of ondansetron is required to control emesis in paracetamol overdose. The papers identified quote doses of 7.5 mg and 8 mg in adults and 0.15 mg/kg in a paediatric patient. The British National Formulary recommends 8 mg intravenous therapy for emetogenic chemotherapy and 4 mg for postoperative nausea.
Bottom Line:
Although ondansetron appears to be effective at treating vomiting secondary to paracetamol overdose, there is currently no direct evidence to support the use of ondansetron as a first-line anti-emetic therapy.
References:
  1. British National Formulary Committee. Section 4.6.. Drugs used in nausea and vertigo.
  2. Clark RF, Chen R, Williams SR, et al.. The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning.
  3. Reed MD, Marx CM.. Ondansetron for treating nausea and vomiting in the poisoned patient.
  4. Scharman EJ.. Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions.
  5. Tobias JD, Gregory DF, Deshpande JK.. Ondansetron to prevent emesis following N-acetylcysteine for acetaminophen intoxication.