Off-label-use of SonoVue in voiding urosonography for the diagnosis of vesicoureteric reflux in children: a survey on side effects

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1 Off-label-use of SonoVue in voiding urosonography for the diagnosis of vesicoureteric reflux in children: a survey on side effects Poster No.: C-0661 Congress: ECR 2014 Type: Scientific Exhibit Authors: A. V. Sauer 1, I. Platzer 1, S. Veldhoen 1, R. Kaiser 2, M. Beer 3, H. Neubauer 1, A. Löser 1, T. A. Bley 1, C. Wirth 1 ; 1 Wuerzburg/DE, 2 Singen/DE, 3 Ulm/DE Keywords: DOI: Drugs / Reactions, Contrast agent-other, Ultrasound, Urinary Tract / Bladder, Kidney /ecr2014/C-0661 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 9

2 Aims and objectives In the last few years many studies have demonstrated the comparable or higher sensitivity of voiding urosonography (VUS) compared to the most common vesicoureteral reflux (VUR) examination, the fluoroscopic voiding cystourethrography (VCUG). Moreover VUS is a nonionising imaging modality. Until its withdrawal in 2011 Levovist (Bayer-Schering Pharma, Berlin, Germany) was commonly used for VUS, which is the most frequent paediatric application of US contrast agent (US-CA). Since that time SonoVue (Bracco Imaging, Milan, Italy) has remained as the only available US-CA in the EU. Unfortunately, it has not been approved for the use in children. SonoVue is a second-generation US-CA composed of stabilized aqueous suspension of sulphur hexafluoride microbubbles with a phospholipid shell. VUS implies the intravesical administration of SonoVue and normal saline. Followed by several scans of the bladder and kidneys during and after bladder filling and finally during voiding. Hereby the observer assess whether microbubles ascend to the ureters and/or the kidneys. In literature there are only a few studies concerning the safety profile of intracavity use of SonoVue in children. There is more data available for the intravenous administration in adults. Here anaphylactoid reactions have been reported at a rate of less than 0.002%. The aim of this ongoing study is to evaluate the risk profile of SonoVue in voiding urosonography in a large cohort of children with suspected or proven VUR. Images for this section: Page 2 of 9

3 Fig. 1: VCUG (left) vs. VUS (right) of bilateral vesicoureteral reflux; the VUS scan shows the US-CA microbubbles in the left renal pelvis (agent detection mode) Page 3 of 9

4 Methods and materials In this prospective study the indication for voiding urosonography was the first confirmed febrile urinary tract infection and the follow-up of previously detected VUR (based on the guidelines of the European Association of Urology/European Society for Paediatric Urology) in children. Parents were informed about the off-label use of SonoVue prior to VUS. There was a written consent for all examinations. Parents were also asked for a standardized telephone survey, which was conducted three days after the VUS by an radiology technician (MTRA). This study was performed in a tertiary care university hospital and a secondary care hospital. The telephone survey was based on a panel of six specific questions/items, where occurance and duration longer than 24 hours were asked for (skin rash, itching, wheals, fever, shortness of breath, consultation of a doctor). Two final questions concerning willingness of repeated VUS with Sono Vue and desire to use VCUG as alternative for forthcomming VUR examinations completed the survey. This ongoing study was performed over a period of 30 month. Images for this section: Page 4 of 9

5 Fig. 2: Protocol for the standardized telephone survey Page 5 of 9

6 Results Between May 2011 and October children (35 male, 305 female; mean age 5.1 years +/- 4.9 years) underwent VUS with intravesical administration of 2.4 +/- 1.1 ml SonoVue. The interviews could be completed for all examined children. No allergic reactions were observed during the examination. In the survey parents described subsequent side effects in 5% (n=17). 2.6% showed unspecific symptoms of illness (n=9; such as feeling of dizzines, symptoms of common cold) and medical consultation was attended in one case. Hints for a potential allergic reaction were reported in 2.4% (n=8; skin irritations, mild fever) and led to a medical consultation in one case. All reported symptoms disappeared within 24 hours. There was no hospital admittance due to allergic reactions. 94.7% of the parents would approve and prefer further VUS examinations with the use of SonoVue. Only 4.4% (n=13) of the parents would agree with VCUG as an alternative imaging modality for further examinations if necessary. Images for this section: Page 6 of 9

7 Fig. 3: Reported side effects Page 7 of 9

8 Conclusion The present study did not show any severe side effects of intravesical administration of SonoVue for VUS in children and reported a high level of acceptance for its off-label-use. This increasing awareness of the negative effects of radiation supports the use of US- CAs also in paediatric imaging. In this context VUS has clinical importance and a high sensitivity for the diagnosis of vesicoureteral reflux. Moreover it seems to have a good safety profile. However, some restrictions of this survey have to be addressed. Although this is an ongoing multi-center study (one tertiary and one secondary care center) cooperation with further departments of paediatric radiology in order to collect more data is necessary. Moreover the duration of this ongoing survey is still limited with 30 month. Additionally the prompted items concerning potential allergic reactions relied in the vast majority on the subjective assessment of parents and not on the consultation of a doctor including additional labaratory data. Nevertheless, the present survey did not show any severe side effect in intravesical administration of SonoVue in children during VUS and no allergic reaction was observed during the examination. Further multicenter surveys with consequently larger cohorts of patients and a systematic clinical assessment of potential allergic reactions after the intravesical administration of SonoVue are necessary. The good safety profile in intravesical use in children, the abscence of ionizing radiation and the high sensitivity and specificity in detection of VUR demonstrates the demand for SonoVue in paediatric radiology and consequently for an approval in paediatric application. Personal information References Riccabona M.: Application of a second-generation US contrast agent Page 8 of 9

9 in infants and children-a European questionnaire-based survey. Pediatr Radiol (2012) 42: Darge K, Grattan-Smith JD, Riccabona M.: Pediatric uroradiology: state of the art. Pediatr Radiol. (2011) Jan; 41 (1) :82-91 Darge K.: Voiding urosonography with US contrast agent for the diagnosis of vesicoureteric reflux in children: an update. Pediatr Radiol (2010) 40: Darge K.: Voiding urosonography with ultrasound contrast agents for the diagnosis of vesicoureteric reflux in children. Pediatr Radiol (2008) 38:40-53 Riccabona M, Avni FE, Blickman JG, Dacher JN, Darge K, Lobo ML, Willi U.: Imaging recommendations in paediatric uroradiology: minutes of the ESPR workgroup session on urinary tract infection, fetal hydronephrosis, urinary tract ultrasonography and voiding cystourethrography, Barcelona, Spain, June Pediatr Radiol. (2008) Feb; 38 (2) : Page 9 of 9