Barrezueta Román, Roxana ValentinaRosales Cevallos, Alexandra ElizabethPalma Sanchez, Ronald Manuel2026-11-112026-11-112026-09Barrezueta Román, R. V., Rosales Cevallos, A. E., & Palma Sanchez, R. M. (2026). Efficacy and safety of systemic morphine for persistent breathlessness in adults with advanced nonmalignant disease: a systematic review and meta-analysis of randomized trials. Palliative Medicine in Practice, 20, e01326063. https://doi.org/10.5603/pmp.1146212545-0425https://biblioteca.solcaquito.org.ec/handle/123456789/1959Background. Morphine is used for persistent breathlessness despite uncertainty about its efficacy and safety in advanced nonmalignant diseases. We evaluated its symptomatic, functional, physiologic, and adverse effects. Methods. We conducted a systematic review of randomized trials comparing systemic morphine with placebo or usual care in adults with persistent breathlessness due to advanced nonmalignant disease. We excluded acute or cancer-related breathlessness and non-systemic administration. PubMed, Embase, Scopus, and Web of Science were searched through July 2026. PRISMA 2020, RoB 2, and GRADE were applied. Random-effects meta-analyses used the Paule–Mandel estimator with Hartung–Knapp adjustment. Results. Of 2,721 records, 15 reports representing 11 independent cohorts and 840 participants were included; five cohorts contributed to six meta-analyses. Compared with placebo, morphine probably results in little to no difference in worst daily-life breathlessness [mean difference (MD), −0.15; 95% confidence interval (CI), −0.63 to 0.34; moderate certainty] and may result in little to no difference in average breathlessness (MD, −0.09; 95% CI, −0.61 to 0.42; low certainty). Evidence for six-minute walk distance and respiratory rate was very uncertain. Changes in oxygen saturation and carbon dioxide tension were small and of low certainty. Several trials reported more adverse events or discontinuations with morphine, but heterogeneity in outcome measurement precluded pooling. Conclusions. Short-term randomized evidence does not support expecting a clinically important benefit of regular oral morphine for daily-life breathlessness. Any therapeutic trial should be individualized, time limited, and closely monitored. Keywords: dyspnea; morphine; analgesics, opioid; palliative care; systematic reviews as topic; randomized controlled trials as topic; meta-analysis as topicenArticle