Gamborg, H., Riis, J., Christrup, L., & Krantz, T. (2013). Effect of intraoral and subcutaneous morphine on dyspnea at rest in terminal patients with primary lung cancer or lung metastases. Journal of Opioid Management, 9, 269–274.

To compare the effectiveness of orally administered red morphine drops (RMD) and subcutaneous morphine (SCM) in patients with advanced lung cancer

Patients were randomized to two groups. Group 1 received oral RMD and a subcutaneous injection of isotonic saline. Group 2 received a placebo oral RMD and a subcutaneous injection of morphine. All injections were given in the leg in a location without edema. Patients were instructed to hold the RMD or placebo RMD solution in their mouths as long as possible before swallowing. The study preparations included a) morphine hydrochloride at 2 g, ethanol 96% at 5 g, cochenille tincture PhD.48 10 g, purified water up to 100 g (one drop corresponded to 0.6 mg morphine), b) ethanol 96% at 5 g, cochenille tincture PhD.48 10 g and purified water up to 100 g, c) injectable morphine 20 mg/ml, and d) isotonic saline. Measurements were taken at baseline and five, 10, 15, 20, 30, and 60 minutes after medication administration. Patients were not allowed to take any opioid within four hours prior to the experiment.

• N = 20  
• MEAN AGE = 69 years (range = 42–84 years)
• MALES: 10%, FEMALES: 90%
• KEY DISEASE CHARACTERISTICS: Lung cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Terminally ill patients receiving opioids for pain; resting dyspnea of at least 3 on 0–10 Visual Analog Scale at rest

• SITE: Single site    
• SETTING TYPE: Not specified  
• LOCATION: Denmark

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Double-dummy randomized, controlled trial

• Visual Analog Scale (VAS) 0–10 to assess the severity of dyspnea
• Respiratory rate
• Oxygen saturation
• Pulse rate

There was no significant difference in dyspnea between the two groups. Both RMD and SCM showed a significant decrease in dyspnea (time p = 0.0451, and treatment p < 0.0001). In addition, RMD and SCM were associated with significant decreases in pulse rate (p = 0.0410). Although it was not statistically significant, patients receiving SCM showed a more rapid decline in dyspnea. Patients in the RMD group received 3.3%–8.6% of their total 24-hour opioid dose. Patients in the SCM group received 1.5%–5.5% of their total 24-hour opioid dose.

Both RMD and SCM improved dyspnea in terminally ill patients.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Other limitations/explanation: Primarily women in the sample; baseline dyspnea was 1 higher in the RMD group

RMD is a reasonable alternative to SCM and should be considered as part of patient preference at the end of life. Subcutaneous administration may provide more rapid relief. It is noteworthy that opioid use relieves dyspnea for patients receiving regular opioids for pain management. The most effective dosage of RMD is not yet known. Additional research to understand the pharmacokinetics of RMD is needed.