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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
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.

Search Outcome

None of the papers identified in the Cochrane search were relevant. Four of the articles identified using Medline were relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Clark 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
Reed et al, 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
Scharman et al, 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 Of those with isolated paracetamol overdose, 59.6% given non-ondansetron anti-emetic failed therapy and 12.5% given ondansetron failed therapy 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)
Tobias et al, 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

Comment(s)

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.

Clinical 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. British National Formulary, 53rd ed. London, UK: Royal Pharmaceutical Society of Great Britain; British Medical Association, 2007 March: 215–21.
2. Clark RF, Chen R, Williams SR, et al. The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning. Clin Toxicol 1996; 34: 163–7.
3. Reed MD, Marx CM. Ondansetron for treating nausea and vomiting in the poisoned patient. Ann Pharmacother 1994; 28: 331–3.
4. Scharman EJ. Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions. Clin Toxicol 1998; 36: 19–25.
5. Tobias JD, Gregory DF, Deshpande JK. Ondansetron to prevent emesis following N-acetylcysteine for acetaminophen intoxication. Paed Emer Care 1992; 8: 345–6.