Safety of intrathecal fluorescein in the repair of anterior skull base fluid fistulas: An umbrella review

Abstract BACKGROUND. The use of intrathecal fluorescein to detect cerebrospinal fluid (CSF) fistulas remains controversial, as it is employed empirically and not authorized for intrathecal administration due to concerns about its safety via this route. OBJECTIVE. This study evaluates the available evidence on the safety of intrathecal fluorescein for diagnosing and localising nasal cerebrospinal fluid leaks. MATERIAL AND METHODS. An umbrella review was independently conducted by two researchers, following the appropriate methodology and PRISMA guidelines, to evaluate the available evidence on the safety of intrathecal fluorescein for diagnosing and localising cerebrospinal fluid leakage. Articles were searched in databases including Scopus, PUBMED, Google Scholar, Mendeley, and ScienceDirect (“intrathecal fluorescein” AND (“CSF fistula” OR “cerebrospinal fluid leak”) AND (“repair” OR “diagnosis”)) from January 2015 to January 2025. Selected articles were evaluated using the ASMTAR Scale 2 rating. RESULTS. Of 446 studies reviewed, only 3 met the inclusion criteria. The results suggest that intrathecal fluorescein is safe when used with proper dosing and protocols, although concerns remain regarding its long-term safety. The need for standardization in dosing and further studies to evaluate chronic effects is emphasized. CONCLUSION. Its use at low doses (10-25 mg) is generally safe, though standardization and long-term data on adverse effects are lacking. Despite its advantages, further research is essential to establish uniform protocols and enhance its safety in clinical practice.