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

J Ultrasound Med. 2017 Mar;36(3):531-538. doi: 10.7863/ultra.15.11075. Epub 2017 Jan 10.


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.

Keywords: adverse reactions; contrast-enhanced sonography; general and abdominal ultrasound; safety; sulfur hexafluoride microbubbles; ultrasound contrast agent.

MeSH terms

  • Abdomen / diagnostic imaging*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Contrast Media / adverse effects*
  • Female
  • Humans
  • Image Enhancement / methods*
  • Male
  • Microbubbles / adverse effects*
  • Middle Aged
  • Phospholipids / adverse effects*
  • Retrospective Studies
  • Sulfur Hexafluoride / adverse effects*
  • Ultrasonography / methods*
  • Young Adult


  • Contrast Media
  • Phospholipids
  • contrast agent BR1
  • Sulfur Hexafluoride