Palliative and Supportive Services, Flinders University, Bedford Park, Australia.
J Palliat Med. 2013 Aug;16(8):881-6. doi: 10.1089/jpm.2012.0591. Epub 2013 Jun 8.
While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern.
This secondary analysis used breathlessness intensity scores (100 mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved <10% improvement over their own baseline at one week (10 mg) were titrated to 20 mg and if no response, another week later to 30 mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling.
Of the 83 participants, 17/52 responders required >10 mg: 13 participants (20 mg) and 4 (30 mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3 mm/day (p=0.16); the average improvement in the first 24 hours of response was 10.9 mm (7.0 to 14.7; p<0.0001), with continued improvement of 2.2 mm/day (p<0.001) for six more days.
When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered.
虽然有证据支持使用缓释吗啡治疗慢性难治性呼吸困难，但对于人们获得症状缓解时呼吸困难强度的纵向模式知之甚少。本研究旨在描述这种模式。
这是一项前瞻性、递增剂量研究的二次分析，该研究评估了每日一次（早晨）缓释吗啡治疗慢性难治性呼吸困难的疗效。对于在一周内（10mg）自身基线水平改善<10%的患者，滴定至 20mg，如果没有反应，一周后再滴定至 30mg，持续一周。时间标准化为参与者开始出现症状缓解的一周的第一天，这会产生症状缓解前后一周的每日两次数据。分析采用随机效应混合模型。
在 83 名参与者中，17/52 名有反应者需要>10mg：13 名参与者（20mg）和 4 名参与者（30mg），共贡献了 634 个 VAS 观察值。在反应前的一周，平均 VAS 评分恶化了 0.3mm/天（p=0.16）；反应开始的前 24 小时平均改善为 10.9mm（7.0 至 14.7；p<0.0001），随后的 6 天每天继续改善 2.2mm（p<0.001）。
在使用每日一次缓释吗啡治疗慢性难治性呼吸困难时，应根据疗效滴定剂量，因为剂量不足可能导致无反应；并且在初始反应后，至少一周内不应再增加剂量。人们对剂量的反应是否会在第六天之后进一步获益，以及进一步增加剂量会有什么净效应，这些问题仍有待回答。
