Off-Label Use of Ultrasound Contrast Agents for Intravenous Applications in Children: Analysis of the Existing Literature.

Abstract

The purpose of this study was to collect and analyze the published data related to intravenous (IV) use of ultrasound (US) contrast agents in children. We searched the literature to collect all of the published studies reporting the IV administration of a second-generation US contrast agent in children. We analyzed 9 case series and 5 case reports, as well as 5 individual cases, of pediatric contrast-enhanced US use reported in a study group that also included adults. We found that 502 children underwent contrast-enhanced US examinations (mean age, 9.7 years; range, 1 day-18 years). Most patients (89%) were injected with the sulfur hexafluoride contrast agent SonoVue (Bracco SpA, Milan, Italy). The mean dose used was 1.5 mL (range, 0.1-9.6 mL). Only 10 patients (2%) had adverse reactions related to the contrast agent administration: 1 life-threatening anaphylactic shock and 9 mild transitory adverse effects. We additionally found 38 papers in which the study groups included at least 1 child; thus, we obtained a total of 540 reported cases of off-label use of IV US contrast agents in children. The most frequent target organ was the liver, and most indications were related to space-occupying lesion characterization and abdominal evaluations after blunt trauma. Some studies also evaluated the diagnostic performance of contrast-enhanced US in different clinical scenarios and found very good accuracy. Concordance between contrast-enhanced US imaging and the respective reference-standard imaging methods ranged between 83% and 100% in different studies. Our results support the idea that the IV use of US contrast agents in children is safe, feasible, diagnostically robust, and effective.