What is the best intervention for fever-related discomfort in children?

In children with fever-associated discomfort, pharmacological interventions appear safe and effective, while physical methods provide limited benefits, suggest the results of a systematic review.

However, “the available evidence is limited by the small number of studies, methodological heterogeneity, and concerns about risk of bias and outcome measurement inconsistency,” the investigators said.

This systematic review followed the PRISMA guidelines. The investigators searched the databases of PubMed, Embase, and Cochrane Library up to 31 January 2025 for studies involving children aged 29 days to 18 years that evaluated interventions for fever-related discomfort. Five randomized controlled trials (RCTs) and three observational studies met the eligibility criteria.

The investigators assessed risk of bias using Cochrane and STROBE tools. They then synthesized results narratively and grouped these according to the type of intervention.

The eight eligible studies included a total of 1,877 children. Variations were noted in research design, including dosage of antipyretics and quality, across studies. [Br J Clin Pharmacol 2025;91:3323-3329]

Studies that compared ibuprofen with paracetamol showed conflicting results, but one trial reported that combination of the two medications appeared more effective than using a single drug. On the other hand, physical methods such as tepid sponging appeared to increase discomfort in children despite reducing body temperature. Serious adverse events were not reported.

“While multiple RCTs have assessed the efficacy of pharmacological and nonpharmacological interventions in lowering body temperature, as summarized in a ... meta-analysis that included 31 RCTs addressing the effects of strategies to reduce body temperature in children with fever, we identified only five RCTs, which considered as outcome the reduction of discomfort,” the investigators said. 

“This gap in research further supports a misalignment between clinical practice guidelines and the available scientific evidence,” they added. [Pediatrics 2024;154:e2023065390; Acta Paediatr 2019;108:1393-1397; Eur J Pediatr 2023;182:651-659]

Discomfort definition

In addition, the available studies varied in the interventions tested, as well as in the tools used to measure discomfort, according to the investigators.

Five studies defined discomfort through behavioural and clinical parameters, such as crying, irritability, shivering, altered sleep–wake cycles, and caregiver-reported sickness behaviour, while other conflated discomfort with pain and provided no clear-cut definition. [Ann Trop Paediatr 1997;17:283-288; J Nepal Paedtr Soc 2018;37:129-133; BMJ 2008;337:a1302; Cureus 2023;15:e46907]

“This variability complicates cross-study comparisons and reflects broader inconsistencies in clinical practice, where subjective interpretations might drive treatment decisions,” the investigators said.

Pharmacological interventions

Paracetamol and NSAIDs, such as ibuprofen, were the most studied drugs, with one study showing ibuprofen to be more effective in relieving discomfort and two others reporting no significant difference between these medications. [Eur J Clin Pharmacol 1997;51:367-371; BMJ 2008;337:a1302; Drugs 1993;46(Suppl 1):231-233]

“Given these mixed findings, further high-quality trials are needed to determine the most effective pharmacological approach for managing discomfort,” the investigators said. 

Furthermore, “the use of paracetamol and ibuprofen was associated in all trials with no or mild adverse events, confirming their well-known safety profile,” they added. 

“By contrast, their use to manage fever-associated discomfort should be cautiously considered in patients at higher risk of adverse events (eg, kidney damage associated to the use of NSAIDs in children with relevant dehydration),” according to the investigators.