Reported safety events from ultrasound enhancing agents: a critical reappraisal.

Abstract

Background: Reported adverse events (AEs) to the Food and Drug Administration Adverse Event Reporting System (FAERS) have suggested an increased rate of serious AEs (SAEs) during the COVID-19 pandemic, but the extent to which this may be related to overall changes in reporting during this time period is uncertain. Accordingly, we aimed to evaluate trends in SAE reporting across commercially available ultrasound enhancing agent (UEA) brands as a function of overall trends in AE reporting.

Methods: We retrospectively analyzed the FAERS public database, 2014-2024, to evaluate risks of UEAs overall and by brand, compared to similar contrast media.

Results: Between 2014 and 2024, 21,960,760 AEs were reported to FAERS, of which 11,450,891 (52.1%) were categorized as SAEs. Overall SAE reports to FAERS increased from 678,953 in 2014 to 1,368,393 in 2021 before subsequently declining to 1,065,845 in 2024 (-7.9% change from 2021 to 2024). During the same period, overall death reports to FAERS increased from 124,055 in 2014 to 195,207 in 2018 before declining to 147,046 in 2024. During this period of decline, there was a 23.9% relative increase in SAEs to UEAs which peaked in 2023 at 350 before declining to 326 in 2024. Deaths attributed to SAEs increased from 1 in 2014 to 19 in 2023 before declining to 9 in 2024. Overall, these data suggest that 11.2% of the observed increase in SAEs to UEAs can be attributed to reporting changes. Despite changes in relative risks for SAEs, absolute SAE rates remained small and lower than other types of contrast media.

Conclusions: In this analysis of the FAERS dataset, 2014-2024, 11.2% of SAEs to UEAs were attributable to temporal changes in AE reporting. Absolute risks are small and declining, suggesting broad safety of UEAs as a class. Collectively, these results support continued use of UEAs, but motivate improved safety screening and preparedness to mitigate small but existing risks.