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Effectiveness and safety of morphine administration for refractory dyspnoea among hospitalised patients with advanced heart failure: the Morphine-HF study
  1. Yasuhiro Hamatani1,
  2. Moritake Iguchi1,
  3. Kenji Moriuchi2,
  4. Yuta Anchi2,
  5. Yasutaka Inuzuka3,
  6. Ryusuke Nishikawa4,
  7. Kiyotaka Shimamura5,
  8. Hirokazu Kondo6,
  9. Hibiki Mima7,
  10. Yugo Yamashita4,
  11. Kensuke Takabayashi8,
  12. Kotoe Takenaka8,
  13. Kengo Korai9,
  14. Yuichi Kawase10,
  15. Ryosuke Murai11,
  16. Hidenori Yaku12,
  17. Kazuya Nagao13,
  18. Mariko Kitano14,
  19. Yuya Aono15,
  20. Takeshi Kitai2,
  21. Yukihito Sato16,
  22. Takeshi Kimura8 and
  23. Masaharu Akao1
  1. 1 Cardiology, National Hospital Organisation Kyoto Medical Center, Kyoto, Japan
  2. 2 Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
  3. 3 Cardiovascular Medicine, Shiga Medical Center for Adults, Moriyama, Japan
  4. 4 Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
  5. 5 Cardiology, Shizuoka General Hospital, Shizuoka, Japan
  6. 6 Cardiology, Tenri Hospital, Tenri, Japan
  7. 7 Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan
  8. 8 Cardiology, Hirakata Kohsai Hospital, Hirakata, Japan
  9. 9 Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan
  10. 10 Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan
  11. 11 Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
  12. 12 Cardiology, Mitsubishi Kyoto Hospital, Kyoto, Japan
  13. 13 Cardiology, Osaka Red Cross Hospital, Osaka, Japan
  14. 14 Cardiovascular Center, Kitano Hospital, Osaka, Japan
  15. 15 Cardiology, Kansai Electric Power Hospital, Osaka, Japan
  16. 16 Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
  1. Correspondence to Dr Yasuhiro Hamatani, Cardiology, National Hospital Organisation Kyoto Medical Center, Kyoto 612-8555, Japan; y.hamatani1114{at}


Objectives Morphine is effective in alleviating dyspnoea in patients with cancer. We aimed to investigate the effectiveness and safety of morphine administration for refractory dyspnoea in patients with advanced heart failure (HF).

Methods We conducted a multicentre, prospective, observational study of hospitalised patients with advanced HF in whom morphine was administered for refractory dyspnoea. Morphine effectiveness was evaluated by dyspnoea intensity changes, assessed regularly by both a quantitative subjective scale (Visual Analogue Scale (VAS; graded from 0 to 100 mm)) and an objective scale (Support Team Assessment Schedule—Japanese (STAS-J; graded from 0 to 4 points)). Safety was assessed by vital sign changes and new-onset severe adverse events, including nausea, vomiting, constipation and delirium based on the Common Terminology Criteria for Adverse Events.

Results From 15 Japanese institutions between September 2020 and August 2022, we included 28 hospitalised patients with advanced HF in whom morphine was administered (mean age: 83.8±8.7 years, male: 15 (54%), New York Heart Association class IV: 26 (93%) and mean left ventricular ejection fraction: 38%±19%). Both VAS and STAS-J significantly improved from baseline to day 1 (VAS: 67±26 to 50±31 mm; p=0.02 and STAS-J: 3.3±0.8 to 2.6±1.1 points; p=0.006, respectively), and thereafter the improvements sustained through to day 7. After morphine administration, vital signs including blood pressure, pulse rate and oxygen saturation did not change, and no new-onset severe adverse events occurred through to day 7.

Conclusions This study suggested acceptable effectiveness and safety for morphine administration in treating refractory dyspnoea in hospitalised patients with advanced HF.

  • Heart failure
  • dyspnoea
  • pharmacology
  • quality of life

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Contributors YH, YY, HY and MA were involved in the conception and study design. MI, KM, YAn, YI, RN, KS, HK, HM, YY, KTaka, KTake, KK, YK, RM, HY, KN, MK and YAo were involved in the data collection process. YH cleaned and analysed the data. YH and MI prepared the original draft. TKit, YS, TKim and MA supervised the original draft. All authors contributed to reviewing and editing the final draft. YH is the guarantor of the content.

  • Funding This study was supported by JSPS KAKENHI (Grant Number JP20K17169) (YH).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.