Off-label-use of sulfur-hexafluoride in voiding urosonography for diagnosis of vesicoureteral reflux in children: A survey on adverse events.

Aim: To evaluate the risk profile of sulfur hexafluoride in voiding urosonography (VUS) based on a large cohort of children.
Methods: Since 2011 sulfur hexafluoride (SH, SonoVue ^® , Bracco, Italy) is the only ultrasound contrast available in the European Union and its use in children has not been approved. Within a 4-year-period, 531 children with suspected or proven vesicoureteral reflux (f/m = 478/53; mean age 4.9 years; 1 mo-25.2 years) following parental informed consent underwent VUS with administration of 2.6 ± 1.2 mL SH in a two-center study. A standardized telephone survey on adverse events was conducted three days later.
Results: No acute adverse reactions were observed. The survey revealed subacute, mostly self-limited adverse events in 4.1% (22/531). The majority of observed adverse events (17/22) was not suspected to be caused by an allergic reaction: Five were related to catheter placement, three to reactivated urinary tract infections, five were associated with perineal disinfection before voiding urosonography or perineal dermatitis and four with a common cold. In five patients (0.9%) hints to a potential allergic cause were noted: Perineal urticaria was reported in three interviews and isolated, mild fever in two. These were minor self-limited adverse events with a subacute onset and no hospital admittance was necessary. Ninety-six point two percent of the parents would prefer future VUS examinations with use of SH.
Conclusion: No severe adverse events were observed and indications of self-limited minor allergic reactions related to intravesical administration of SH were reported in less than 1%.
Competing Interests: Conflict-of-interest statement: Thorsten Bley: Consultancy for GSK and MSD; Speakers bureau: Bayer, Bracco, GE, Guerbet, HeartFlow, Siemens; Research funding: Deutsche Forschungsgesellschaft DFG: BL 1132/1-2; Research cooperation: Siemens, Noras, Rapid. The remaining authors of this manuscript have no conflicts of interest to disclose.