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Word of the Day

Evidence for combination antipyretics is limited

Clinical Question:
Are combinations of antipyretics more effective than single agents in treating febrile children?

Bottom Line:
Overall, only a few studies have evaluated combinations of antipyretics. Although the existing studies were of reasonable quality, and a few found some signs that combination treatment might be better than a single agent at controlling fever, the differences are small and no study has shown that children are better off. (LOE = 2a-)

Purssell E. Systematic review of studies comparing combined treatment with paracetamol and ibuprofen, with either drug alone. Arch Dis Child 2011;96(12):1175-1179.  [PMID:21868405]

Study Design:
Systematic review

Unknown/not stated

Various (meta-analysis)

This author flew solo and searched MEDLINE, Embase, and the references of the American Academy of Pediatrics and the United Kingdom National Institute for Health and Clinical Excellence guidelines for managing fever to identify randomized trials comparing the effectiveness of any dose of combined paracetamol (acetaminophen) and ibuprofen versus either drug alone. The author used the CONSORT statement to assess the quality of the included studies. The main outcomes of interest were fever control, comfort measures, and evidence of side effects or toxicity. The author identified 7 studies with CONSORT scores ranging from 17 to 22 points (of a possible 22 points). Unfortunately, the author never tells us how many patients were in the studies. The included studies were highly variable in dosages, follow up, and definitions for temperature response. No study that reported temperature changes found a difference between combined treatment and monotherapy in the first 3 hours, but combined treatment lowered temperature slightly more at 4 and 5 hours (0.6 and 0.8 degrees Celsius), but not at 6 hours. The proportion of children who become afebrile is similar at 6 hours, while slightly more children using combination medication became afebrile by 8 hours, even though the maximum temperature decline was about the same. Only 2 studies assessed the parents' perceptions of their children's comfort. One study found no difference, while the other reported that there was no difference on the first day but that combination treatment was slightly better on subsequent days.


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