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

Sissel Kronborg-White, Charlotte Uggerhøj Andersen, Charlotte Kohberg, Ole Hilberg, Elisabeth Bendstrup, Sissel Kronborg-White, Charlotte Uggerhøj Andersen, Charlotte Kohberg, Ole Hilberg, Elisabeth Bendstrup

Abstract

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.

Keywords: Interstitial lung disease; Morphine; Palliation.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of the study. Vitals: pulse, blood pressure, respiratory rate; PFT: pulmonary function test; VAS: visual analogue scale; 6 MWT: 6 min walking test
Fig. 2
Fig. 2
Changes in VAS dyspnea score during the previous week and questionnaires from baseline to follow-up. Box and whiskers plot of change in VAS dyspnea score during the previous week (a), KBILD score (b), GAD7 score (c), and Leicester cough score (d) from baseline to follow-up

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