Safety of the contrast enhancement agent sulfur hexafluoride in ultrasound: Analysis of the Federal Drug Administration Adverse Event Reporting System database

Abstract

Background and Objectives Sulfur hexafluoride is an inert gas that creates microbubbles to enhance diagnostic accuracy in a variety of ultrasound (US) studies and is widely used in EUS. We analyzed the reported adverse events (AEs) of the US contrast agent, sulfur hexafluoride, extensively used during EUS procedures using a US national database. Methods From December 2008 to January 2024, AEs reported in the Federal Drug Administration Adverse Event Reporting System database for sulfur hexafluoride were examined. Results There were 1069 individual reports analyzed. Reports were excluded if they contained drugs other than sulfur hexafluoride. Echocardiogram (70.9%) was the common diagnostic study in which sulfur hexafluoride was administered. The most common AE reported was anaphylactic reaction (n = 179, 16.7%), followed by hypotension (n = 162, 15.2%), cardiac arrest (n = 161, 15.1%), and dyspnea (n = 159, 14.9%). The most common gastrointestinal AE was nausea (n = 135, 12.6%). Severity of AEs ranged from nonserious to death. Death associated with sulfur hexafluoride use was reported in 58 patients (5.4% of AE reports). Conclusions Anaphylactic reaction was the most common AE reported with sulfur hexafluoride use, and severe AEs including death may be more common than prior large, retrospective, observational studies to date have suggested.