Adverse dose-dependent effects of morphine therapy in acute heart failure

Int J Cardiol. 2019 Oct 15:293:131-136. doi: 10.1016/j.ijcard.2019.06.015. Epub 2019 Jun 12.

Abstract

Background: Morphine has been a pivotal therapy in acute heart failure (AHF) for more than a century. The evidence for morphine therapy in AHF remains controversial. This study sought to assess the therapeutic effect of morphine on patients with AHF.

Methods: The study used a cohort of 13,788 patients admitted with a primary diagnosis of AHF. Propensity-score-matching was generated using 26 clinical variables. Primary endpoints included in-hospital mortality and invasive mechanical ventilation. Secondary endpoints included non-invasive ventilation, need for inotropes and acute kidney injury (AKI).

Results: 761 (5.5%) patients were treated with morphine in the first day following hospital admission. Propensity score matching yielded 672 patient pairs. The incidence of invasive ventilation was higher in the morphine-treated patients (7.4%) than in matched patients in the no-morphine cohort (3.6%), OR 2.13 (95% CI 1.32-3.57, P = 0.007). In-hospital mortality was also higher in the morphine group (17.4%) than in the matched no-morphine group (13.4%), OR 1.43 (95% CI 1.05 to 1.98, P = 0.024). For both the endpoint of invasive ventilation (Ptrend = 0.005) and mortality (Ptrend = 0.004), there was a significant linear dose-response relationship for the adverse effect of morphine. Morphine was associated with a significant increase in all secondary outcomes: Non-invasive ventilation (OR 2.78, 95% CI 1.95-3.96); Inotrope use (OR 3.50, 95% CI 2.10-5.82) and AKI (OR 1.81, 95% CI 1.39-2.36). A landmark analysis demonstrated no difference in post-discharge survival between cohorts.

Conclusions: Morphine administration is associated with significant dose-dependent risk for in-hospital mortality and need for mechanical ventilation.

Keywords: Heart failure; Mechanical ventilation; Opiates.

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Cohort Studies
  • Databases, Factual / trends
  • Dose-Response Relationship, Drug
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality*
  • Heart Failure / surgery
  • Hospital Mortality / trends*
  • Humans
  • Male
  • Middle Aged
  • Morphine / administration & dosage
  • Morphine / adverse effects*
  • Retrospective Studies

Substances

  • Analgesics, Opioid
  • Morphine