Elsevier

International Journal of Cardiology

Volume 202, 1 January 2016, Pages 870-873
International Journal of Cardiology

Review
Morphine in the treatment of acute pulmonary oedema — Why?

https://doi.org/10.1016/j.ijcard.2015.10.014Get rights and content

Highlights

  • Morphine has commonly been used in the treatment of pulmonary oedema.

  • Studies indicate that morphine may cause harm in patients with acute pulmonary oedema.

  • The evidence for a vasodilatory effect is poor.

  • Reliable studies must clarify the role of morphine in pulmonary oedema.

Abstract

Morphine has for a long time, been used in patients with acute pulmonary oedema due to its anticipated anxiolytic and vasodilatory properties, however a discussion about the benefits and risks has been raised recently. A literature search in Medline and Embase using the keywords “pulmonary oedema” OR “lung oedema” OR “acute heart failure” AND “morphine” was performed. A certain vasodilation has been described after morphine administration, but the evidence for this mechanism is relatively poor and morphine-induced anxiolysis may possibly be the most important factor of morphine in pulmonary oedema and therefore some authors have suggested benzodiazepines as an alternative treatment. Respiratory depression seems to be a less relevant clinical problem according to the literature, whereas vomiting is common, which may cause aspiration. In the largest outcome study, based on the ADHERE registry, morphine given in acute decompensated heart failure was an independent predictor of increased hospital mortality, with an odds ratio of 4.8 (95% CI: 4.52–5.18, p < 0.001). Other, smaller studies have shown a significant association between morphine administration and mortality, which was lost after adjusting for confounding factors.

Morphine is still used for pulmonary oedema in spite of poor scientific background data. A randomised, controlled study is necessary in order to determine the effect – and especially the risk – when using morphine for pulmonary oedema. Since the positive effects are not sufficiently documented, and since the risk for increased mortality cannot be ruled out, one can advocate that the use should be avoided.

Introduction

Acute pulmonary oedema is a common condition in the emergency room, associated with considerable mortality [1], [2]. The oedema develops when the left ventricle fails, making the hydrostatic pressure in the pulmonary circulation increase, and therefore fluid builds up in the pulmonary insterstitium and alveoli. The condition is defined by severe respiratory distress that worsens in supine position, crackles over the lung and signs of pulmonary congestion on chest X-ray [3]. Peripheral oxygen saturation is usually below 90% prior to treatment.

Pharmacological treatment of pulmonary oedema aims at treating the increased hydrostatic pressure in the pulmonary circulation, primarily by lowering filling pressure (preload), and by lowering the peripheral arterial pressure (afterload) — achieved through venous and arterial dilation [4]. Traditionally there has also been emphasis on removing excess fluid through increased diuresis [5].

Since the 1960s, three drugs have been most frequently used to achieve these effects, alongside oxygen treatment. It is furosemide, which inhibits reabsorption of sodium in Henle's loop and distal tubuli and thereby increasing excretion of fluids through the kidney. Then there is nitroglycerin, which via cGMP and smooth muscle relaxation induces vasodilatation — at low doses only venous, at high doses also causing arterial relaxation [6], [7].

The third drug, morphine, has been used due to its anticipated anxiolytic and vasodilatory properties. During the last decade, a discussion about the benefits and especially the risks accompanying the use of morphine in cases of pulmonary oedema has been raised [1], [4], [8], [9], [10], [11]. In a retrospective study from 2008 based on the ADHERE registry, morphine given in acute decompensated heart failure was an independent predictor of increased hospital mortality, with an odds ratio of 4.8 (95% CI: 4.52–5.18, p < 0.001) [2].

A literature search in Medline using the keywords “pulmonary oedema” OR “lung oedema” OR “acute heart failure” AND “morphine” was performed. The search was conducted in February 2014 and gave 263 results. A similar search was performed in Embase, where Medline articles were excluded and the search was limited to articles written in English (191 results). We were particularly interested in studies that documented the outcome after using morphine in the treatment of acute pulmonary oedema as well as studies and review articles in which the physiological effects of the drug were discussed. A total of 24 articles were discretionarily picked out after reviewing abstracts [2], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26].

Section snippets

Guidelines

The European heart failure guideline from 2012 state that one can consider giving 4–8 mg of morphine intravenously (repeated as needed) if the patient suffers from severe anxiety or distress caused by pulmonary oedema (Fig. 1) [27]. The American Heart Failure Society does not include morphine in its recommendations from 2010 and comments that the drug should be used with caution if administered [28]. The collaboration American College of Cardiology Foundation/American Heart Association does not

Physiological effects of morphine

Morphine induces depression of the central nervous system via opiate receptors in the brain, which causes both sedation and analgesia [12]. In addition to this, morphine has a supposed anxiolytic effect, which together with the sedative effect reduces the activity of the sympathetic nervous system and causes a reduction of both the filling pressure and the arterial pressure [4].

It is believed that morphine has a vasodilating effect in pulmonary oedema [3], [13], [28]. The background of this

Adverse physiological effects

The most common adverse effects of morphine are constipation and nausea. While constipation has no significance in acute medical context, it is described that between one-fifth and one-third of patients experience nausea when using opioids [35], [36]. Vomiting occurs about half as frequently as nausea. European guidelines recommend the addition of 10 mg of metoclopramide to counteract nausea if morphine is administered [27]. Nausea in pulmonary oedema is a disadvantageous side effect because of

Heterogeneous prognoses

In a review article from 2008 Sosnowski [11] emphasises that there seems to be a correlation between the use of morphine and worsening of the patient's condition, based on five studies from 1987 to 2003 [10], [21], [22], [23], [24]. One of these is a small trial of prehospital treatment of pulmonary oedema. It showed that 38% of patients treated with morphine and furosemide, experienced subjective deterioration compared with none of the patients who received nitroglycerin and furosemide [10].

Conclusion

Morphine is still used for pulmonary oedema in spite of relatively poor scientific background data. A randomised, controlled study is necessary in order to determine the effect – and especially the risk – when using morphine for pulmonary oedema. Since the positive effects are not sufficiently documented, and since the risk for increased mortality cannot be ruled out, one can advocate that the use should be avoided.

Conflict of interest

C. Ellingsrud: No conflict of interest. S. Agewall: Speaker fees, Honoraria, Consultancy, Advisory Board fees from AstraZeneca, ThermoFischer, Boehringer Ingelheim.

References (42)

  • N. Rawal et al.

    Present state of extradural and intrathecal opioid analgesia in Sweden. A nationwide follow-up survey

    Br. J. Anaesth.

    (1987)
  • J.C. Huffman et al.

    The use of benzodiazepines in the treatment of chest pain: a review of the literature

    J. Emerg. Med.

    (2003)
  • A. Gray et al.

    Diuretic, opiate and nitrate use in severe acidotic acute cardiogenic pulmonary oedema: analysis from the 3CPO trial

    QJM

    (2010)
  • W.F. Peacock et al.

    Morphine and outcomes in acute decompensated heart failure: an ADHERE analysis

    Emerg. Med. J.

    (2008)
  • M.S. Nieminen et al.

    Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology

    Eur. Heart J.

    (2005)
  • S. Grayson et al.

    CHF treatment: is furosemide on the way out? Rethinking the pulmonary edema cocktail

    EMS World

    (2012)
  • J.C. Coons et al.

    Pharmacotherapy for acute heart failure syndromes

    Am. J. Health Syst. Pharm.

    (2011)
  • M. Hall et al.

    Is morphine indicated in acute pulmonary oedema?

    Emerg. Med. J.

    (2005)
  • G.N. Cattermole et al.

    Opiates should be avoided in acute decompensated heart failure

    Emerg. Med. J.

    (2009)
  • M.A. Sosnowski

    Review article: lack of effect of opiates in the treatment of acute cardiogenic pulmonary oedema

    Emerg. Med. Australas.

    (2008)
  • M.R. Johnson

    Acute pulmonary edema

    Curr. Treat. Options Cardiovasc. Med.

    (1999)
  • Cited by (27)

    • Clinical outcomes of opioid administration in acute and chronic heart failure: A meta-analysis

      2022, Diabetes and Metabolic Syndrome: Clinical Research and Reviews
      Citation Excerpt :

      The observed increased risk for in-hospital mortality indicates that morphine use may alleviate treatment effectiveness during hospitalization and that it is acutely harmful. In addition to its vasodilatory properties, the use of morphine as an anxiolytic (owing to its sedative properties) also explains its use as part of the treatment for breathlessness in patients with AHF [45–47]. However, our meta-analysis of breathlessness scores among patients with AHF was not significant.

    • Pre-treatment with morphine prevents lipopolysaccharide-induced acute respiratory distress syndrome in rats via activation of opioid receptors

      2022, Experimental Cell Research
      Citation Excerpt :

      Opioid analgesics, such as morphine, primarily bind to mu-opioid receptor (MOR) [8]. In addition, morphine has been applied in patients with acute pulmonary edema for a long time because of its anticipated anxiolytic and vasodilatory properties [9]. Therefore, we suspected that morphine could exert similar pulmonary protective effects against ARDS by binding to MOR in the brain.

    • Phytomedicine and phytonanocomposites-An expanding horizon

      2021, Phytomedicine: A Treasure of Pharmacologically Active Products from Plants
    • Misconceptions in acute heart failure diagnosis and Management in the Emergency Department

      2018, American Journal of Emergency Medicine
      Citation Excerpt :

      For example, morphine may have been given more frequently to patients with more severe heart failure. Also, determining if morphine was actually associated with increased intubation versus use as a sedative after intubation is difficult to ascertain [105]. Though there are confounders, physicians have many other options to improve preload and afterload in pulmonary edema and AHF, such as NIPPV and nitrate therapy [54,57,58].

    View all citing articles on Scopus
    View full text