Potential Efficacy of Midazolam as Second-Line Treatment for Terminal Dyspnea in Patients with Cancer: Secondary Analysis of a Multicenter Prospective Cohort Study

Introduction: Opioids are widely used as first-line treatment for dyspnea in terminally-ill patients with advanced cancer (terminal dyspnea), but the merit of second-line treatment for persistent terminal dyspnea despite opioid titration is not clear. Objectives: To explore whether the adjunctive us...

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Main Authors: Satoru Miwa, Masanori Mori, Takashi Yamaguchi, Kozue Suzuki, Yoshinobu Matsuda, Ryo Matsunuma, Hiroaki Watanabe, Tomoo Ikari, Yoshihisa Matsumoto, Kengo Imai, Naosuke Yokomichi, Toshihiro Yamauchi, Soichiro Okamoto, Satoshi Inoue, Akira Inoue, Tatsuya Morita, Eriko Satomi
Format: Article
Language:English
Published: Mary Ann Liebert 2024-10-01
Series:Palliative Medicine Reports
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Online Access:https://www.liebertpub.com/doi/10.1089/pmr.2023.0076
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Summary:Introduction: Opioids are widely used as first-line treatment for dyspnea in terminally-ill patients with advanced cancer (terminal dyspnea), but the merit of second-line treatment for persistent terminal dyspnea despite opioid titration is not clear. Objectives: To explore whether the adjunctive use of low-dose midazolam as second-line treatment for terminal dyspnea is associated with dyspnea relief compared with further opioid titration. Methods: In this preplanned secondary analysis of a multicenter prospective cohort study that consecutively enrolled patients with advanced cancer and terminal dyspnea, we included patients with persistent dyspnea despite opioid titration for whom palliative care physicians added low-dose midazolam (≤10 mg/day) continuously as adjunctive treatment (midazolam group) or titrated opioids further (opioid group). We examined dyspnea intensity (Integrated Palliative care Outcome Scale; IPOS) at the baseline and after six hours. Results: Of the 108 patients enrolled in the main study, 19 exhibited persistent dyspnea despite opioid titration. Four patients were treated with low-dose midazolam, and 15 were treated with further opioid titration. The mean dyspnea IPOS scores decreased from 3.3 [standard error (SE) = 0.2] to 1.3 (0.05) [difference = 2.0 (95% confidence interval [CI] = −0.1 to 3.9); p = 0.07] in the midazolam group and significantly decreased from 2.7 (0.1) to 1.3 (0.2) [difference = 1.4 (95% CI = 0.8 to 2.0); p < 0.001] in the opioid group. No significant between-group differences were noted in the mean IPOS scores at the baseline or after six hours. Treatment-related adverse events were rare. Conclusion: Continuous low-dose midazolam as adjunctive treatment to opioids may serve as second-line treatment for persistent terminal dyspnea. Future randomized-controlled trials are warranted.
ISSN:2689-2820