Relief of Incident Dyspnea in Palliative Cancer Patients: A Pilot, Randomized, Controlled Trial Comparing Nebulized Hydromorphone, Systemic Hydromorphone, and Nebulized Saline

Acute episodic breathlessness in patients receiving palliative care is a distressing symptom with little evidence-base to inform management. This pilot, double-blind, controlled, crossover study compared the effects of nebulized hydromorphone, systemic hydromorphone and nebulized saline for the relief of episodic breathlessness in advanced cancer patients. On three occasions of acute breathlessness, patients randomly received either nebulized hydromorphone, a systemic breakthrough dose of hydromorphone or nebulized saline together with a blinding agent. Breathlessness was scored before and 10, 20, 30, and 60 minutes post-treatment completion using a 100 mm visual analog scale. Twenty patients completed the trial. Ratings did not differ significantly across pretest treatments. Change in ratings from pretest to 10 minutes after completion of nebulization (about 20 minutes after administration of systemic hydromorphone) indicated that each of the treatments resulted in statistically significant improvements in breathlessness, with no significant differences between treatments. Over time, breathlessness decreased significantly for all treatments, with no significant differences between treatments. Only nebulized hydromorphone produced a rapid improvement in breathlessness that reached a magnitude considered to be clinically important. Interpretation of these results is considered in relation to our definition of clinical significance, the dose of hydromorphone used and the possibility of a placebo effect. This study can serve to inform the design of future trials to investigate the management of incident breathlessness.