Late Breaking Abstract - Morphine for dyspnea in advanced pulmonary arterial hypertension

Abstract

Background: Whether morphine is useful for improving dyspnea and exercise capacity in advanced pulmonary arterial hypertension (PAH) is unclear. Methods: Patients with PAH with WHO FC III symptoms despite therapy were enrolled in a randomized, cross-over study of oral morphine sulfate 5mg versus no drug prior to two six-minute walk tests (6MWT) performed within 7 days. The primary outcome was peak Borg dyspnea score. Safety outcomes were symptom scores and changes in vital signs. Data were analyzed using a paired t-test. Results: 12 patients were enrolled and 2 were withdrawn (one due to syncope on a control 6MWT and one due to intercurrent illness). Among those completing the study, median disease duration was 4.6 years and 90% were on dual or triple targeted PAH therapy. The peak Borg dyspnea score did not differ with morphine versus control (4.7 vs 5.0, p=0.34). Borg scores at 2, 4 and 6 minutes of the 6MWT were lower with morphine but did not reach statistical significance. The mean 6MWD was 349m with morphine versus 342m with control (p=0.38). No significant differences in clinically important symptoms or side effects were detected with morphine. Changes in systolic blood pressure response (+22 vs +11mmHg, p=0.18), heart rate response (+38 vs +35bpm, p=0.36), and nadir oxygen saturation (86 vs 86%, p=1) with exercise did not differ (morphine vs control). Conclusion: Oral morphine did not improve peak dyspnea scores or exercise capacity in patients with advanced PAH. The improvement in submaximal dyspnea scores with morphine did not achieve statistical significance. Limitations relate to small subject numbers and absence of blinding. Morphine was not associated with side effects or worsening of vital signs.