Morphine versus midazolam as upfront therapy to control dyspnea perception in cancer patients while its underlying cause is sought or treated

Context: Cancer patients with dyspnea may be able to have the symptom pharmacologically controlled while its underlying cause is sought or treated.

Objectives: This study was done to determine whether symptom control can be achieved while the cause is evaluated or treated and whether morphine or midazolam would be more suitable in this setting.

Methods: Sixty-three ambulatory patients with advanced cancer and dyspnea were clinically characterized and then randomized to receive either oral morphine or oral midazolam. A fast in-clinic drug titration scheme was implemented followed by an ambulatory five-day period in which the patients received the effective dose that relieved their dyspnea. During this period, the patients were followed daily while the underlying causes of dyspnea were sought out or treated.

Results: Thirty-one patients with dyspnea entered the morphine arm and 32 patients entered the midazolam one. During the initial in-clinic phase, dyspnea was alleviated by at least 50% in all patients, whether they received morphine or midazolam. During the ambulatory phase, midazolam was superior to morphine in controlling baseline and breakthrough dyspnea. Both treatments were well tolerated, with mild somnolence being the most common adverse event. Neither morphine nor midazolam affected the outcome and/or implementation of additional diagnostic and/or therapeutic interventions.

Conclusion: Our results suggest that cancer-related dyspnea in ambulatory patients can be pharmacologically treated while its most probable specific cause is sought and/or while an etiology-oriented intervention is implemented. In this setting, midazolam appeared to be a better option than morphine for the immediate and long-term relief of the symptom.