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Anticholinergic drugs for death rattle in dying patients with cancer: multicentre prospective cohort study
  1. Takashi Yamaguchi1,
  2. Naosuke Yokomichi2,
  3. Takuhiro Yamaguchi3,
  4. Isseki Maeda4,
  5. Ryo Matsunuma5,
  6. Yukako Tanaka-Yagi5,
  7. Asami Akatani1,
  8. Kozue Suzuki6,
  9. Hiroyuki Kohara7,
  10. Tomohiko Taniyama8,
  11. Yosuke Matsuda9,
  12. Nobuhisa Nakajima10,
  13. Tatsuya Morita2,
  14. Satoru Tsuneto11 and
  15. Masanori Mori2
  1. 1 Department of Palliative Medicine, Kobe University Graduate School of Medicine School of Medicine, Kobe, Hyogo, Japan
  2. 2 Department of Palliative and Supportive Care, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
  3. 3 Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
  4. 4 Department of Palliative Care, Senri Chuo Hospital, Toyonaka, Osaka, Japan
  5. 5 Department of Palliative Care, Konan Medical Center, Kobe, Hyogo, Japan
  6. 6 Department of Palliative Care, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
  7. 7 Department of Palliative Care, Hatsukaichi Memorial Hospital, Hatsukaichi, Hiroshima, Japan
  8. 8 Department of Oncology and Palliative Care, Mitsubishi Kyoto Hospital, Kyoto, Japan
  9. 9 Department of Palliative Care, St Luke's International University, Chuo-ku, Tokyo, Japan
  10. 10 Division of Community Medicine and Internal Medicine, University of the Ryukyus Hospital, Nishihara, Okinawa, Japan
  11. 11 Department of Palliative Medicine, Kyoto University, Kyoto, Japan
  1. Correspondence to Professor Takashi Yamaguchi, Department of Palliative Medicine, Kobe University Graduate School of Medicine School of Medicine, Kobe 650-0017, Hyogo, Japan; ikagoro{at}


Background This study aimed to investigate the effectiveness of anticholinergics (AC) for death rattle in dying patients with cancer.

Methods This is a prospective cohort study enrolled Terminally ill adult (20 years or older) patients with cancer who developed substantial death rattle (Back score ≥2) from 23 palliative care units in Japan. AC treatment for death rattle was prescribed according to primary physician’s decision. The primary outcome was the proportion of patients whose death rattle improved, which was defined as a Back score of ≤1. We compared the proportion of improved cases in patients treated with (AC group) and without (non-AC group) AC, controlling potential confounders by employing propensity score weighting.

Results Of the 1896 patients enrolled, we included 196 who developed a substantial death rattle. Of these, 81 received AC. 56.8% in the AC group and 35.4% in the non-AC group had an improved death rattle at 8 hours after baseline. In the weighted analysis, AC group showed significant improvements in death rattle, with an adjusted OR of 4.47 (95% CI 2.04 to 9.78; p=0.0024). All sensitivity analyses achieved essentially the same results. In the subgroup analysis, ACs were strongly associated with death rattle improvement in men, patients with lung cancer, and type 1 death rattle (adjusted OR 5.81, 8.38 and 9.32, respectively).

Conclusions In this propensity score-weighted analysis, ACs were associated with death rattle improvement in terminally ill patients with cancer who developed substantial death rattle.

Trial registration number UMIN-CTR (UMIN00002545).

  • End of life care
  • Hospice care
  • Terminal care

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  • Contributors TY, IM, TM, ST and MM were responsible for conception and design. RM, AA, YT-Y, KS, HK, TT, YM and NN were responsible for collection and assembly of data. TY, NY, TY and MM were responsible for data analysis and interpretation. All authors were responsible for manuscript writing and final approval of manuscript.

  • Funding This study was supported by JPPS KAKENHI (Grant number 21H02829) and a Grant-in-Aid from the Japan Hospice Palliative Care Foundation.

  • Disclaimer The sponsor did not involve the study design, the collection and management of the data, and manuscript writing.

  • 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.