CLINICAL QUESTION

Is a single dose of a combination of ibuprofen and acetaminophen better than either treatment alone for fever in children?

BOTTOM LINE

Although there are good arguments against treating fever associated with a presumed infection, alternating or combined treatment with acetaminophen and high-dose ibuprofen seems to be better than either treatment alone, with a number needed to treat of 3 to 4 for short-term benefit. (Level of Evidence = 1a−)

SYNOPSIS

The authors followed PRISMA guidelines for a network meta-analysis and searched three databases (including Cochrane CENTRAL) with two clinical trial registries, Google Scholar, and conference abstracts. They identified 31 randomized controlled studies of 5,009 children that compared ibuprofen (high and low dose) with acetaminophen, separately, alternating, or together to reduce the presence of fever and discomfort after a single dose in an outpatient setting. A network analysis allowed the authors to compare response rates among studies that did not directly compare all options. For fever clearance after 4 hours and 6 hours, combined and alternating therapies were more effective than ibuprofen alone, which was more effective than acetaminophen alone. In six studies that evaluated general patient discomfort, the scores were not different among treatments. Parent discomfort has not been studied. The risk of bias was high for some studies and concerning for others—only one study was deemed to be at low risk. An analysis that excluded studies with high risk of bias did not show different results.