Prospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Pediatr. Feb 8, 2017; 6(1): 52-59
Published online Feb 8, 2017. doi: 10.5409/wjcp.v6.i1.52
Off-label-use of sulfur-hexafluoride in voiding urosonography for diagnosis of vesicoureteral reflux in children: A survey on adverse events
Alexander Sauer, Clemens Wirth, Isabel Platzer, Henning Neubauer, Simon Veldhoen, Alexander Dierks, Reinhard Kaiser, Andreas Kunz, Meinrad Beer, Thorsten Bley
Alexander Sauer, Clemens Wirth, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
Isabel Platzer, Henning Neubauer, Simon Veldhoen, Alexander Dierks, Andreas Kunz, Thorsten Bley, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
Reinhard Kaiser, Department of Pediatrics, Hegau-Bodensee-Hospital Singen, 78224 Singen, Germany
Meinrad Beer, Department of Diagnostic and Interventional Radiology, University Hospital Ulm, 89081 Ulm, Germany
Author contributions: Wirth C and Beer M designed the research; Sauer A, Wirth C, Platzer I, Neubauer H, Veldhoen S, Dierks A Kaiser R and Beer M performed the research; Sauer A, Wirth C, Platzer I, Neubauer H, Veldhoen S, Dierks A and Bley T analyzed the data; Sauer A performed statistical analysis and wrote the manuscript; Kunz A was responsible for language editing; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Medical Faculty of the University of Wuerzburg.
Informed consent statement: All study participants, or their legal guardian, provided written consent prior to study enrollment.
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.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Alexander Sauer, Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Wuerzburg, Oberduerrbacher Straße 6, 97080 Wuerzburg, Germany. sauer_a4@ukw.de
Telephone: +49-40931-201634001
Received: June 13, 2016
Peer-review started: June 13, 2016
First decision: July 4, 2016
Revised: October 26, 2016
Accepted: November 16, 2016
Article in press: November 17, 2016
Published online: February 8, 2017
Processing time: 235 Days and 10.7 Hours
Abstract
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%.

Keywords: Voiding urosonography; Ultrasound contrast agent; Vesicoureteral reflux; SonoVue; Adverse events; Sulfur hexafluoride

Core tip: This was a two-center study on 531 children with suspected or proven vesicoureteral reflux undergoing off-label voiding urosonography using sulfur hexafluoride (SH). We investigated the SH risk profile with intravesical administration. No acute allergic adverse event was observed with the off-label-use of SH for radiation free assessment of vesicoureteral reflux. Only a few subacute, minor-to-moderate adverse events were reported (4.1%). Hints of self-limited minor allergic reaction related to intravesical administration of sulfur hexafluoride were reported in less than 1%. This underlines the demand for an approval of SH in pediatric applications.