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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. [ABSTRACT FROM AUTHOR]