Blinded Patient Preference for Morphine Compared to Placebo in the Setting of Chronic Refractory Breathlessness--An Exploratory Study

Abstract

Context: Patients' preference for morphine therapy has received little attention in the setting of chronic refractory breathlessness. However, this is one important factor in considering longer term therapy.

Objectives: The aim of this secondary analysis was to explore blinded patient preference of morphine compared to placebo for this indication and to define any predictors of preference.

Methods: Data were pooled from three randomized, double-blind, crossover, placebo-controlled studies of morphine (four days each) in chronic refractory breathlessness. Blinded patient preferences were chosen at the end of each study. A multivariable regression model was used to establish patient predictors of preference.

Results: Sixty-five participants provided sufficient data (60 men; median age 74 years; heart failure 55%, chronic obstructive pulmonary disease 45%; median Eastern Cooperative Oncology Group performance status 2). Forty-three percent of participants preferred morphine (32% placebo and 25% no preference). Morphine preference and younger age were strongly associated: odds ratio = 0.85, 95% confidence interval 0.78-0.93; P < 0.001). There was also an inverse association between morphine preference and sedation (odds ratio = 0.77, 95% confidence interval 0.60-0.99; P < 0.05). An inverse association was also seen between nausea and morphine preference in the univariate model only (P < 0.05). No association was seen between morphine preference and breathlessness intensity, either at baseline or change from baseline.

Conclusion: Participants preferred morphine over placebo for the relief of chronic refractory breathlessness. Morphine offers clinically important improvement, but net benefit can be easily outweighed by side effects, reducing net benefits. Side effects require aggressive management to allow more patients to realize benefits.

Keywords: COPD; Patient preference; breathlessness; morphine; palliative care; randomized controlled trial.