Zeppetella, G. (1997). Nebulized morphine in the palliation of dyspnoea. Palliative Medicine, 11, 267–275.

Nebulized morphine 20 mg mixed with 2 mL of saline was administered using a face mask every four hours for 48 hours.

• The sample was comprised of 17 patients in hospice care with nonreversible dyspnea, either at rest or on exertion, associated with primary or secondary malignant intrathoracic disease; six patients also had chronic obstructive pulmonary disease (COPD).
• Mean age was 68 years.
• Of the patients, 12 (71%) were male.
• Thirteen patients were already taking opioids.
• Fourteen patients completed the trial.

Unknown but assumed to be in a hospital

The study used an open, uncontrolled, nonrandomized design.

The Dyspnea Assessment Questionnaire (DAQ) and a recalled 24-hour visual analog scale (VAS) were used. Three subscales of the DAQ—Total Severity Score, Percentage Total Severity Score (PTSS), and Dyspnea Quality-Quantity Score (DQQS)—were also analyzed. DQQS was the primary outcome measure. Measurements were taken at baseline (one hour before the first dose of nebulized medication) and were repeated at 24 and 48 hours.

Sixteen patients (94%) reported significantly lower (p = 0.0005) DQQS scores at 24 hours. The four opioid-naïve patients showed no significant benefit from the nebulized treatment. (The theory is that the prevalence of binding receptors in airways is influenced by systemic use of opioids.) Improvement appeared greater in the qualitative aspect of dyspnea as shown by PTTS versus VAS. Benefits were noted at 24 hours and did not improve from there. Change in DQQS scores from 24 to 48 hours was not significant (p-value not given).

Qualitative aspects of dyspnea improved more than quantitative aspects.

• The study had a small sample size.
• Due to the uncontrolled nature of the study, the placebo effect cannot be ruled out.
• One patient refused to participate after the first dose, reporting claustrophobia.
• Fourteen patients completed the trial. Three patients dropped out after 24 hours (two because of a dislike for the nebulizer and one because of weakness); otherwise, no significant side effects were reported.
• Six patients who discontinued nebulized treatments after 24 hours did so because of weakness. Weakness appeared to reduce the acceptability of the nebulized intervention.