Impact of morphine use in acute cardiogenic pulmonary oedema on mortality outcomes: a systematic review and meta-analysis

Background: Morphine is commonly used in the management of acute cardiogenic pulmonary oedema. The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) do not recommend the routine use of opioids in acute heart failure (AHF) due to dose-dependent side effects. However, the effect of morphine remains unclear. Our study aims to investigate the link between morphine use in acute cardiogenic pulmonary oedema and mortality. Methods: PubMed and Embase databases were searched from inception to October 2021. All studies were included (randomized, non-randomized, observational, prospective and retrospective). The references for all the articles were reviewed for potential articles of interest with no language restrictions. Studies looking at in-hospital mortality along with other outcomes were chosen. The Newcastle–Ottawa scale was used to appraise the studies. Heterogeneity was assessed using I2. Meta-analysis was conducted using the Review Manager Software version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), by computing odds ratios (ORs) for pooled in-hospital mortality and clinical outcomes. Results: Six observational studies out of the 73 publications identified were eligible for the meta-analysis giving a total sample size of 152,859 (mean age 75, males 48%). Of these, four were retrospective analyses. The use of morphine in acute cardiogenic pulmonary oedema was associated with an increased rate of in-hospital mortality [OR = 2.39, confidence interval (CI) = 1.13 to 5.08, p = 0.02], increased need for invasive ventilation (OR = 6.14, CI = 5.84 to 6.46, p < 0.00001), increased need for non-invasive ventilation (OR = 1.85, CI = 1.45 to 2.36, p < 0.00001) and increased need for vasopressors/inotropes (OR = 2.93, CI = 2.20 to 3.89, p < 0.00001). Conclusion: Based on the observational studies, morphine use in acute cardiogenic pulmonary oedema is associated with worse outcomes. Further randomized controlled trials are needed to confirm any causative effect of morphine on mortality rates in acute cardiogenic pulmonary oedema.