Lack of evidence for a beneficial effect of antipyretic drugs.

‘During the time we used (a pure antipyretic in Vienna), not only was this disease not shortened in its duration…but, on the contrary, it ran a more protracted course’ was a reply to Medical Records, New York, 1886;30(15): 415. This paragraph illustrates the already long history of debate surrounding studies on antipyretics published in medical journals. We thank the recent study by Milani et al.1 to try to untangle the knot that is strangling fever, which enhances the immune response and induces stress on pathogens. We would like to take this opportunity to express our opinion in line with this old idea that fever has existed longer than antipyretic drugs and that while some fish or lizards will intentionally raise their temperature in response to infection, humans are the only species that will intentionally lower their temperature in this situation. Contrary to their statement that they aim to implement educational interventions to avoid misconceptions about antipyretics and to ensure that medical students subscribe in the long term to evidence-based management of the feverish child, Milani et al. teach their students that they should consider the child's discomfort (rather than body temperature) as a valid criterion for treating fever. A 2002 Cochrane review concludes that it is not clear whether paracetamol is effective when compared to placebo or physical methods in fever reduction, and a 2013 Cochrane review2 reports that the only trial that assessed child discomfort found no difference in this measure between the treatment regimens (paracetamol plus ibuprofen, paracetamol alone or ibuprofen alone). Most research has examined evidence of the benefits and harms of reducing fever through descriptive analyses or experimental animal studies. Conversely, Kramer et al.3 conducted a double-blind trial of symptoms such as hunger, fluid intake, mood or comfort in 226 febrile children randomly treated with a placebo or paracetamol; only 52% of parents were able to correctly guess that their child took the placebo, and 45% of them guessed that their child took paracetamol; a coin toss would have resulted in a more precise outcome. Since one cannot conclude that antipyretic drugs would improve outcomes for distressed febrile children, a more evidence-based, less ambivalent and less confusing approach would be to educate medical students that fevers generally are harmless; antipyretics provide no known benefit to children with fever and feeling unwell, and even that in either the short or long term may be to their detriment. This study was not supported by any funders. Sergio Verd contributed to concept and design. Marianna Mambié contributed to acquisition, analysis or interpretation of data. Carla Rodríguez-Trabal contributed to drafting of the first manuscript. All authors have been involved in drafting the final manuscript and revising it critically and have given final approval of the version to be published. No disclosures were reported.