Long-term health effects of antipyretic drug use in the ageing population: protocol for a systematic review

Background: Fever is suppressed with drugs due to discomfort and risk of organ damage. However, there is some compelling evidence for the benefits of fever. The elderly are a special population in this regard as they have a blunted fever response. The benefit-harm balance of antipyretic use in this population is unclear.   This study aims to provide the synthesized best evidence regarding long-term health effects of antipyretic treatment in the elderly during infections, investigating the onset/worsening of common chronic diseases, for e.g., thyroid disorders, connective tissue diseases and chronic obstructive pulmonary disease/asthma. Methods: A systematic review will be performed to establish the best evidence available regarding antipyretic treatment in the elderly, searching databases such as Medline, Embase and Cochrane CENTRAL from their inception till date for all types of studies. Studies that consider the drugs in analgesic role will be excluded. The search will be reported following the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) guidelines. Randomized control trials, quasi experimental studies, observational studies, case series and reports will be included. The primary outcome measure being onset/worsening of chronic inflammatory diseases. Other outcomes include relief of symptoms, length of hospital stay, patient satisfaction, mortality, blood/immune parameters indicative of morbidity and complications of the infection. Risk of biases in randomized studies will be assessed through the Cochrane risk of bias tool. For other study types, appropriate tools such as CASP/QUIPS/Cochrane non-randomised studies tool will be used. Meta-analysis will be conducted on the Cochrane RevMan software and where pooling of data is not possible, a narrative synthesis will be performed. Overall certainty of evidence will be assessed through the GRADE approach. Discussion: The study aims to provide evidence regarding benefit-harm balance of antipyretic use in the elderly population to inform clinical practice and future research.  Systematic review registration: PROSPERO CRD42020160854.