Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers.

OBJECTIVES: We aimed to evaluate the safety of the ultrasound contrast agent sulfur hexafluoride microbubbles in a large group of patients referred for routine contrast-enhanced ultrasound (CEUS). METHODS: A retrospective assessment was made of all patients that received sulfur hexafluoride microbubbles intravenously for CEUS at 24 centers between January 2006 and April 2019. Patient demographic details, examination type, and the dose of sulfur hexafluoride microbubbles administered were recorded with specific adverse events (AEs) documentation tools at each center. All AEs were recorded as serious or non-serious. Non-serious AEs were classified by intensity as mild, moderate, or severe according to ACR criteria. The frequencies of AEs across patient subgroups were compared using the chi-square test. RESULTS: A total of 463,434 examinations were evaluated. Overall, 157 AEs (153 [0.033%] non-serious; 4 [0.001%] serious) were reported after sulfur hexafluoride microbubbles administration, giving an AE frequency of 0.034% (157/463,434). Among the non-serious AEs, 66 (0.014%) were mild, 70 (0.015%) moderate, and 17 (0.004%) severe in intensity. The liver was the most common examination site, presenting an AE frequency of 0.026%. The highest AE frequency (0.092%) was for patients undergoing CEUS for vascular disease. There were no significant gender differences in either the total number or the severity of non-serious AEs (chi-square = 2.497, p = 0.287). The onset of AEs occurred within 30 min of sulfur hexafluoride microbubbles administration in 91% of cases. CONCLUSION: The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare, confirming that sulfur hexafluoride microbubbles are appropriate for routine CEUS applications. KEY POINT: • The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare.

Safety of Sulfur Hexafluoride Microbubbles in Sonography of Abdominal and Superficial Organs: Retrospective Analysis of 30,222 Cases.

OBJECTIVES: The purpose of this study was to investigate the safety of the sulfur hexafluoride microbubble contrast agent SonoVue (Bracco SpA, Milan, Italy) and to implement precautions with the intent of further improving the safety of this contrast agent. METHODS: A total of 30,222 patients undergoing contrast-enhanced sonography of abdominal and superficial organs in our hospital from January 2005 to December 2014 were retrospectively investigated. SonoVue was used as the ultrasound contrast agent. The symptoms and treatments of adverse reactions occurring during the contrast-enhanced sonographic examinations were reviewed and analyzed. RESULTS: No patient died as a result of any adverse reaction. Six patients (0.020%) had adverse reactions of varying degrees, including 2 patients (0.007%) who had signs of early anaphylactic shock (chest tightness, palpitations, sweating, and rapid and weak pulse, followed by cyanosis, a disappearing pulse, and a drop in blood pressure) that improved after active rescue. The remaining 4 patients developed the following: redness and a rash on the arm above the injection site, nasal bleeding and nausea, nausea and vomiting, and back pain with numbness of the lips and limbs. Symptoms in these 4 patients self-resolved after a period of rest. CONCLUSIONS: Contrast-enhanced sonography with sulfur hexafluoride microbubbles had good clinical safety, but rare adverse reactions were observed. A comprehensive emergency plan and rescue measures for adverse reactions should be prepared and made available to minimize the occurrence of negative clinical outcomes.

A retrospective study on adverse events of intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications in 83,778 patients.

OBJECTIVES: To investigate the rate of adverse events (AEs) caused by intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications retrospectively and to explore practical measures for prevention and treatment of them. MATERIALS AND METHODS: This study enrolled 83,778 contrast-enhanced ultrasound (CEUS) examinations using sulfur hexafluoride microbubbles intravenously performed during 11 years. Age, gender, and target organs of all CEUS patients were recorded. For cases of AEs, their medical history and laboratory results were also collected. The process of AEs was assessed and categorized. Besides, the management of AEs were recorded. RESULTS: Twenty patients had sulfur hexafluoride microbubbles-related AEs. The AE rate was 0.024%. No significant difference was observed between patients with AEs and the whole group for age and sex distribution. All AEs happened in liver examinations. Among them, 7 (35%) were mild, 8 (40%) were moderate, and 5 (25%) were severe. They were categorized into 15 allergic-like reactions and 5 physiologic reactions. The manifestations of mild and moderate AEs mainly include urticaria, chills, and mild hypoxia, which could be eased by simple management. Severe cases had anaphylactic shock, generalized convulsions, and diffuse erythema with hypotension respectively. They need close monitoring and oxygen inhalation with anti-shock and anti-anaphylactic treatment. Most cases started within 30 min and recovered within 1 day. CONCLUSIONS: Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications was safe with rare AEs. AEs were more likely to happen in abdominal applications than superficial ones. A well-designed emergency plan should be available for clinical use of sulfur hexafluoride microbubbles to reduce AEs and to deal with AEs properly. CRITICAL RELEVANCE STATEMENT: Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications reported few AEs and could be considered safe but severe AEs are life-threatening. We analyzed the influence factors of AEs and propose some methods for prevention and treatment of them, which can further improve the safety of sulfur hexafluoride microbubbles in clinical practice. KEY POINTS: • The AE rate of sulfur hexafluoride microbubbles in abdominal and superficial applications was 0.024%. • Patients were more likely to have AEs in abdominal applications than superficial ones. • Severe AEs are life-threatening and need prompt identification and treatment. • We summarized some detailed suggestions for clinical prevention and treatment of AEs.

Improving Prognostic and Chronicity Evaluation of Chronic Kidney Disease with Contrast-Enhanced Ultrasound Index-Derived Peak Intensity.

The capability of contrast-enhanced ultrasound (CEUS) to assess the prognosis and chronicity of chronic kidney disease (CKD) was evaluated in patients diagnosed with CKD in 2014 at Ren Ji Hospital, Shanghai, China. Time-intensity curves and quantitative indexes were created using QLab quantification software. Kidney biopsies were analyzed with α-smooth muscle actin immunohistochemistry. According to the renal chronicity score, patients were divided into four groups: minimal (n = 14), mild (n = 73), moderate (n = 49) and severe (n = 31). Multivariate logistic regression analysis revealed that the derived peak intensity (DPI) was independently associated with the renal chronicity score. Of 167 CKD patients (median follow-up: 30.4 ± 18.7 mo), 31 (18.6%) exhibited CKD progression, with a decline in the glomerular filtration rate of more than 25% or end-stage renal disease. Multivariate Cox regression analysis revealed that a lower DPI was independently associated with CKD progression. This study indicates that DPI is a reliable CEUS parameter for evaluating chronic renal changes and an independent prognostic factor of CKD.