PURPOSE Episodic breathlessness is frequent in palliative cancer patients. Opioids are the only pharmacological agents with sufficient evidence in treatment. In Denmark, the main recommendation is red morphine drops (RMD), an off-label solution of morphine, ethanol, and red color (cochenille) described since 1893 (Pharmacopoea Danica). In 2015, the Danish Medicines Agency increased focus on off-label medicines and recommended registered morphine drops without ethanol instead. However, our palliative patients told us that RMD was better. For that reason, we conducted a clinical trial to clarify any perceived difference between the two types of drops. METHODS We conducted a randomized, double blinded, crossover trial. Patients were asked to perform standardized activity (2-min walk) aiming to provoke breathlessness. Primary endpoint (breathlessness NRS) and secondary endpoints (saturation, pulse, respiratory frequency) were measured before (t = 0) and after test medicine at t = 1, t = 3, t = 5, t = 10, and t = 20 min. After 2-4 days (washout period), the patients repeated the test, receiving the alternative drops in a blinded setup (crossover). RESULTS In the first 3 min, the relative drop in breathlessness for morphine drops with ethanol (RMD) was significant more than for morphine drops without ethanol. We found no significant difference in secondary endpoints. CONCLUSIONS A conclusion could be that ethanol might facilitate morphine absorption in the mouth. Our results needs further research of opioid absorption in the mouth as well as trials, testing morphine vs. more lipophilic opioids. The RMD drops are cheap, easy to use, and noninvasive and keep the patient independent of health care professionals.

中文翻译：

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口服吗啡滴剂可快速缓解晚期癌症患者的呼吸困难-硫酸吗啡口服滴眼液与盐酸吗啡滴眼液与乙醇（红色吗啡滴眼液）的随机，双盲，交叉试验。

目的在姑息性癌症患者中经常发生阵发性呼吸困难。阿片类药物是唯一在治疗中有充分证据的药物。在丹麦，主要推荐使用红色吗啡滴剂（RMD），这是自1893年以来就被描述的吗啡，乙醇和红色（cochenille）的脱标签溶液（Pharmacopoea Danica）。2015年，丹麦药品管理局（Danish Medicines Agency）更加注重非标药物，并建议注册不含乙醇的吗啡滴剂。但是，我们的姑息患者告诉我们RMD更好。因此，我们进行了一项临床试验，以弄清两种滴剂之间的任何可察觉差异。方法我们进行了一项随机，双盲，交叉试验。要求患者进行标准化的活动（步行2分钟），以引起呼吸困难。在t = 1，t = 3，t = 5，t = 10和t = 20的测试药物之前（t = 0）和之后测量主要终点（呼吸困难NRS）和次要终点（饱和度，脉搏，呼吸频率）分钟 2-4天（冲洗期）后，患者重复测试，并在不知情的情况下接受替代滴剂（交叉）。结果在开始的3分钟内，含乙醇的吗啡滴剂（RMD）的相对呼吸困难度明显高于不含乙醇的吗啡滴剂。我们发现次要终点没有显着差异。结论结论可能是乙醇可能促进吗啡在口腔中的吸收。我们的结果需要进一步研究阿片类药物在口腔中的吸收以及试验，以测试吗啡与更多的亲脂性阿片类药物。RMD滴剂价格便宜，易于使用，