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

  • Contrast Media
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Abstract

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.

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Abbreviations

ACR:

American College of Radiology

AEs:

adverse events

CEUS:

Contrast-Enhanced Ultrasound

UEAs:

Ultrasound Enhancing Agents

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Funding

This study has received funding from the International Science & Technology Cooperation Program of China (No. 2015DFA30920), the National Natural Science Foundation of China (No. 81771856), and the Major Field Technical Innovation Program Project of the Affiliated Hospital of Army Medical University (No. SWH2016ZDCX4101).

Author information

Authors and Affiliations

  1. Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China

    Yongning Shang, Chunlin Tang, Deng Liu, Kejing Fang & Yanli Guo

  2. Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute for the Study of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Xiaoyan Xie

  3. Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu, China

    Yan Luo

  4. Department of Medical Ultrasonics, Lanzhou University Second Hospital, Lanzhou, China

    Fang Nie

  5. Department of Ultrasound, Chinese PLA General Hospital, Beijing, China

    Yukun Luo

  6. Department of Ultrasound, Tianjin Third Central Hospital, Tianjin, China

    Xiang Jing

  7. Department of Medical Ultrasonics, Xiang Ya Hospital, Central South University, Changsha, China

    Jintang Liao

  8. Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    Rongqin Zheng

  9. Department of Ultrasound in Medical, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Rong Wu

  10. Department of Medical Ultrasound, Yunnan Cancer Hospital, Kunming, China

    Xiaomao Luo

  11. Department of Ultrasound Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

    Zhiyi Chen

  12. Department of Ultrasound, Ningbo First Hospital, Ningbo, China

    Youfeng Xu

  13. Department of Medical Ultrasonics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Ruifang Zhang

  14. Department of Ultrasound, China-Japan Union Hospital, Jilin University, Changchun, China

    Hui Wang

  15. Department of Ultrasonography, The People’s Hospital of Zhengzhou University, Zhengzhou, China

    Jianjun Yuan

  16. Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Hongxia Zhang & Wen He

  17. Department of Ultrasound, Peking University People’s Hospital, Beijing, China

    Jiaan Zhu

  18. Department of Ultrasound, The Third Affiliated Hospital of Guangxi Medical University, Nanjing, China

    Wei Zhang

  19. Department of Ultrasound Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China

    Litao Ruan

  20. Department of Ultrasound, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

    Min Yang

  21. Department of Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

    Zhiyan Li

  22. Department of Ultrasound, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

    Hong Luo

  23. Department of Ultrasonic Medicine, West China Second University Hospital, Sichuan University, Chengdu, China

    Qin Chen

  24. Department of Ultrasound, People’s Hospital of Shanxi Province, Taiyuan, China

    Jiping Yan

  25. Department of Ultrasound, Southwest Hospital, Army Medical University (Third Military Medical University), Gaotanyan street No.30, Shapingba Distract, Chongqing, China

    Yanli Guo

  26. Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili No.6, Dongcheng District, Beijing, China

    Wen He

Authors
  1. Yongning Shang
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  2. Xiaoyan Xie
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  3. Yan Luo
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  4. Fang Nie
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  5. Yukun Luo
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  6. Xiang Jing
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  8. Rongqin Zheng
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  9. Rong Wu
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  10. Xiaomao Luo
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  13. Ruifang Zhang
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  14. Hui Wang
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  15. Jianjun Yuan
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  16. Hongxia Zhang
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  17. Jiaan Zhu
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  18. Wei Zhang
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  19. Litao Ruan
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  20. Min Yang
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  21. Zhiyan Li
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  22. Hong Luo
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  23. Qin Chen
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  24. Jiping Yan
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  25. Chunlin Tang
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  26. Deng Liu
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  27. Kejing Fang
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  28. Yanli Guo
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  29. Wen He
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Corresponding authors

Correspondence to Yanli Guo or Wen He.

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Guarantor

The scientific guarantor of this publication is Yanli Guo M.D. (Department of Ultrasound, Southwest Hospital, Army Medical University, Chongqing, 400038, China) and Wen He M.D. (Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China).

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in J Ultrasound Med. In the prior study, we reported on 30 222 patients included in the current study. The prior report evaluated the rate of adverse reactions. The current study expands on this by having a larger patient number and a multicenter study.

Methodology

• retrospective

• observational

• multicenter study

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Shang, Y., Xie, X., Luo, Y. et al. Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers. Eur Radiol 33, 988–995 (2023). https://doi.org/10.1007/s00330-022-09108-4

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