Objectives To assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with viral respiratory infections on acute severe adverse outcomes, healthcare utilisation, quality of life and long-term survival.
Design Rapid systematic review.
Participants Humans with viral respiratory infections, exposed to systemic NSAIDs.
Primary outcomes Acute severe adverse outcomes, healthcare utilisation, quality of life and long-term survival.
Results We screened 10 999 titles and abstracts and 738 full texts, including 87 studies. No studies addressed COVID-19, Severe Acute Respiratory Syndrome or Middle East Respiratory Syndrome; none examined inpatient healthcare utilisation, quality of life or long-term survival. Effects of NSAIDs on mortality and cardiovascular events in adults with viral respiratory infections are unclear (three observational studies; very low certainty). Children with empyema and gastrointestinal bleeding may be more likely to have taken NSAIDs than children without these conditions (two observational studies; very low certainty). In patients aged 3 years and older with acute respiratory infections, ibuprofen is associated with a higher rate of reconsultations with general practitioners than paracetamol (one randomised controlled trial (RCT); low certainty). The difference in death from all causes and hospitalisation for renal failure and anaphylaxis between children with fever receiving ibuprofen versus paracetamol is likely to be less than 1 per 10 000 (1 RCT; moderate/high certainty). Twenty-eight studies in adults and 42 studies in children report adverse event counts. Most report that no severe adverse events occurred. Due to methodological limitations of adverse event counts, this evidence should be interpreted with caution.
Conclusions It is unclear whether the use of NSAIDs increases the risk of severe adverse outcomes in patients with viral respiratory infections. This absence of evidence should not be interpreted as evidence for the absence of such risk. This is a rapid review with a number of limitations.
PROSPERO registration number CRD42020176056.
- adverse events
- respiratory infections
- clinical pharmacology
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Contributors PvP and ER developed the protocol with input from all review authors, and PvP coordinated the overall review process. PvP took the lead in putting together the report, supported by ER and all review authors. All other review authors are listed in alphabetical order, with every single one having made significant contributions, both intellectually and in terms of time commitment. JMS and PvP developed the search strategy and conducted the searches. AM, BS, JB, JMS, KG, KS, LMP, PvP, RB and SD screened studies for eligibility, extracted data and assessed risk of bias. AM, ER, JB, JMS and PvP conducted the GRADE assessment. All review authors contributed to the narrative and tabular evidence synthesis and manuscript preparation.
Funding Funded through staff positions and other funds of the Ludwig-Maximilians-Universität München (LMU Munich).
Disclaimer This systematic review was requested by the WHO. The authors alone are responsible for the views expressed in this systematic review and they do not necessarily represent the decisions, policy or views of the WHO.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information. The data supporting the conclusions of this article are included within the article and its additional file.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.