Tanaka, K., Shima, Y., Kakinuma, R., Kubota, K., Ohe, Y., Hojo, F., . . . Nishiwaka, Y. (1999). Effect of nebulized morphine in cancer patients with dyspnea: a pilot study. Japanese Journal of Clinical Oncology, 29, 600–603.

To test the theory that the local benefit of opioids is related to opioid binding sites in peripheral bronchus.

Patients were given 20 mg of morphine dissolved in 5 mL of normal saline administered through an ultranebulizer. If no subjective relief resulted, the dose was increased to 40 mg and was tried again after four hours.

• The sample was comprised of 15 patients with thoracic cancer without cognitive changes who had dyspnea that was difficult to control with standard treatment (e.g., pleural drainage, antibiotics, and diuretics). 
• Median age was 61 years. 
• Seven patients were on continuous oxygen by cannula.
• Ten patients were already on systemic opioids.

Inpatient hospital in Japan

This was a pilot, open-label, nonrandomized, uncontrolled study.

• Dyspnea visual analog scale (VAS) was measured at baseline and at 60 minutes after inhalation.
• Outcome criteria was an improvement greater than 10% decrease in VAS.
• Respiratory rate (RR), hemoglobin, and oxygen saturation were also measured.
• A questionnaire about adverse effects and preferences was administered.

Significant decrease occurred in VAS after nebulization (p = 0.005). Eight of 15 patients evaluated treatment effective and requested continuation. No significant change occurred in RR or oxygenation. A not statistically significance tendency was found for patients on systemic opioids to benefit more compared to nonopioid patients.

• The study had a small sample size and was uncontrolled.
• The intervention placebo effect cannot be ruled out.
• The dose increase without a washout period possibly contaminated the findings.