Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

Abstract

Heart failure affects nearly 65million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151735 participants), resulting in 15 more per 1000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09- 6.80; low certainty of evidence; four observational studies, n=167847 participants), resulting in 45 more per1000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews ortrials. Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.