title: Off-label-use of sulfur-hexafluoride in voiding urosonography for diagnosis of vesicoureteral reflux in children: A survey on adverse events.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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%.
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sauer
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Wirth
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Platzer
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Neubauer
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Veldhoen
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dierks
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kaiser
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kunz
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Beer
authors.affiliation: Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Bley
keywords: Adverse events; SonoVue; Sulfur hexafluoride; Ultrasound contrast agent; Vesicoureteral reflux; Voiding urosonography