Evaluating the safety of oral methylene blue during swallowing assessment: a systematic review

B. Tariq*, S.R. Simon, W. Pilz, A. Maxim, B. Kremer, L.W.J. Baijens

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review


Objective Methylene blue (MB) is frequently administered during fiberoptic endoscopic evaluation of swallowing (FEES) to enhance visualization of pharyngeal bolus transit. However, the safety of MB is being questioned since serious adverse events (AEs) such as hemodynamic instability, hemolysis, and serotonin syndrome were reported. The aim of this study is a systematic analysis of the literature to obtain an evidence-based overview of AEs due to oral administration of MB and to determine its safety as a food dye during swallowing assessment. Methods A systematic literature search was carried out in PubMed, Embase, and Cochrane Library. Two reviewers independently selected articles describing oral administration of MB as a main diagnostic/therapeutic intervention, dosage, and AEs. Expert opinions, conference papers, sample size < 10, and animal studies were excluded. Level of evidence of the included studies was determined. Results A total of 2264 unduplicated articles were obtained. Seventeen studies met the inclusion criteria with 100% agreement between the two reviewers. Among these, twelve studies were randomized controlled trials. In a pooled population of 1902 patients receiving oral MB, three serious AEs were reported related to MB. Non-serious AEs showed a dose-related trend and were usually mild and self-limiting. A meta-analysis could not be performed as studies were methodologically too heterogeneous. Conclusion Serious AEs due to oral administration of MB are rare (n = 3, 0.16%). MB-related non-serious AEs are mild, self-limiting, and show a dose-related trend. These findings indicate that it is safe to use small amounts of MB as a food dye during swallowing examinations.
Original languageEnglish
Pages (from-to)3155-3169
Number of pages15
JournalEuropean Archives of Oto-Rhino-Laryngology
Issue number9
Early online date2 Jan 2021
Publication statusPublished - Sept 2021


  • adverse events
  • aspiration
  • bioavailability
  • chloroquine
  • combination
  • controlled-trial
  • dye procedure
  • dysphagia
  • efficacy
  • fiberoptic endoscopic evaluation
  • fiberoptic endoscopic evaluation of swallowing
  • methylene blue
  • safety
  • uncomplicated falciparum-malaria
  • videofluoroscopy
  • Fiberoptic endoscopic evaluation of swallowing
  • Adverse events
  • Dysphagia
  • Safety
  • Methylene blue

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