The safety of morphine in patients with acute heart failure: A systematic review and meta-analysis

Clin Cardiol. 2021 Sep;44(9):1216-1224. doi: 10.1002/clc.23691. Epub 2021 Jul 8.


While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether the application of morphine to those patients is reasonable. We aim to conduct a systematic review and meta-analysis to assess the safety of morphine in patients with AHF. We searched PubMed, Cochrane Library, and Embase electronic databases from inception through March 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes. Seven studies with 172, 226 patients were included. The results showed that morphine usage was not associated with increased in-hospital mortality (OR: 1.94; 95% CI 0.93 to 4.03; p = 0.08). However, the use of morphine significantly increased the risk of invasive ventilation (OR: 2.72; 95% CI 1.09 to 6.80; p = 0.03). Furthermore, the subgroup analysis indicated that the application of morphine was not associated with increased 7-day all-cause mortality in patients with AHF (OR: 1.69; 95% CI 0.80 to 3.22; p = 0.11) but significantly increased the risk of 30-day all-cause mortality (OR: 1.59; 95% CI 1.16 to 2.17; p = 0.004). Based on current evidence, our results suggested that although morphine therapy did not significantly increase the risk of short-term death (in the hospital or within 7 days) in patients with AHF, the risk of long-term death and invasive ventilation were significantly increased. This result needs to be further confirmed by an ongoing randomized control trial.

Keywords: acute heart failure; all-cause mortality; in-hospital mortality; invasive ventilation; morphine.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Hospital Mortality
  • Humans
  • Morphine* / adverse effects


  • Morphine