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

OBJECTIVES: 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. METHODS: We searched the literature to collect all of the published studies reporting the IV administration of a second-generation US contrast agent in children. RESULTS: 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. CONCLUSIONS: Our results support the idea that the IV use of US contrast agents in children is safe, feasible, diagnostically robust, and effective.