Palliation of chronic breathlessness with morphine in patients with fibrotic interstitial lung disease – a randomised placebo-controlled trial

BACKGROUND: Patients suffering from fibrotic interstitial lung diseases (fILD) have a poor prognosis and a high symptom burden. Palliative treatment includes relief of symptoms such as breathlessness. There is no evidence-based treatment for chronic breathlessness but opioids are often used despite concerns due to the hypothetical risk of respiratory depression. This study investigated the effect of oral morphine drops in patients with fILD on chronic breathlessness and safety. METHODS: In a double-blinded placebo-controlled study, 36 patients with fILD were randomised to either four daily doses of 5 mg of oral morphine drops or placebo for 1 week. Endpoints and safety parameters were obtained at baseline, at follow-up after 1 h and 1 week. RESULTS: The primary endpoint, the visual analogue score (VAS) of dyspnea was reduced by 1.1 ± 0.33 cm in the morphine group at follow-up compared to baseline (P < 0.01), whereas the reduction was 0.35 ± 0.47 cm in the placebo group. However, the difference between the two groups was not statistically significant (p = 0.2). Oral morphine drops did not affect respiratory frequency, pulse rate, blood pressure, peripheral saturation or the 6-min walk test. More patients treated with morphine reported constipation, nausea and confusion. CONCLUSION: Oral administration of morphine drops, 20 mg a day, in patients with fILD did not significantly reduce dyspnea VAS score during 1 week compared to placebo. Oral morphine did not induce respiratory depression, but was related to an increased risk of constipation, nausea and confusion. TRIAL REGISTRATION: The trial is registered in clinicaltrials.gov (Identifier: NCT02622022). Registered 4 December 2015.