Bruera, E., Sala, R., Spruyt, O., Palmer, J. L., Zhang, T., & Willey, J. (2005). Nebulized versus subcutaneous morphine for patients with cancer dyspnea: a preliminary study. Journal of Pain and Symptom Management, 29, 613–618.

To compare subcutaneous (SC) injection versus nebulized morphine (median dose of 45 mg, equal to half of the scheduled equivalent opioid dose) on two separate days; because nebulized morphine is thought to have rapid onset of action and low systemic absorption, adverse effects may be avoided.

• The sample was comprised of 11 patients. 
• Median age was 58 years.
• Patients were included if they
  • Had dyspnea (at least 3 on a scale of 0–10 in which 10 = worst dyspnea not related to acute complication) and advanced cancer with no clinical evidence of bronchospasm (predominant restrictive ventilation)
  • Were receiving regular oral or parenteral opioids
  • Had normal cognition.

The study used a double-blind, randomized crossover trial design.

• Dyspnea self-reports on a 0–10 scale were measured at baseline (end of one hour of rest) and every 15 minutes for 1.5 hours and then every 30 minutes for the next three hours.
• The main outcome was dyspnea score at 60 minutes.
• Blind preference of treatment was assessed by patients and investigators.

Significant improvement occurred in dyspnea scores from baseline to 60 minutes measured at 15-minute intervals for both SC (dyspnea score decreased from 5 to 3; p = 0.025) and nebulized morphine (dyspnea score decreased from 4 to 2; p = 0.007). No significant difference was found between SC and nebulized morphine for each time period. Bronchospasm was not observed in the nebulized treatment group.

Both routes were effective in this sample. The number of patients was insufficient to determine a difference between the routes.

• The study had a very small sample size and insufficient power to rule out a significant difference between the two routes.
• Recruiting patients with continuous dyspnea (at rest) was very difficult.