Morphine Use in the Treatment of Acute Cardiogenic Pulmonary Edema and Its Effects on Patient Outcome: A Systematic Review

  • Víctor GilEmail author
  • Alberto Domínguez-Rodríguez
  • Josep Masip
  • W. Frank Peacock
  • Òscar Miró
Emergency Medicine (Frank Peacock, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Emergency Medicine


Purpose of Review

To analyze whether the use of morphine, as initial treatment in acute cardiogenic pulmonary edema (ACPE), has an impact in clinical outcomes and mortality. A systematic review of the literature was performed, including all the studies comparing clinical outcomes in patients with ACPE who were treated or not with morphine.

Recent Findings

Seven studies were selected, none of which were a randomized trial focused on answering the aim of this systematic review. The studies consisted of clinical trial secondary analysis assessing non-invasive ventilation in ACPE, one open non-randomized trial, two propensity score evaluations from large registries, and three clinical case reviews. Most of the studies showed unfavorable results with the use of morphine in terms of adverse events and mortality, and many of them were statistically significant. Finally, the ongoing MIdazolam versus MOrphine in acute cardiogenic pulmonary edema (MIMO) trial was specifically designed to compare the results of morphine use versus midazolam.


The potential hemodynamic and sedative benefit of the use of morphine for vasodilatation and dyspnea amelioration may be opposed by an increase in mortality, ICU admission, and adverse events. Until there is a randomized clinical trial, the use of morphine for ACPE should be limited.


Heart Failure Acute Cardiogenic Pulmonary Edema Morphine Outcomes 



This study was partially supported by grants from the Instituto de Salud Carlos III supported with funds from the Spanish Ministry of Health and FEDER (PI15/01019, PI15/00773, PI18/00393, PI19/00456) and Fundació La Marató de TV3 (2015/2510). The “Emergencies: Processes and Pathologies” research group of the IDIBAPS receives financial support from the Catalonian Government for Consolidated Groups of Investigation (GRC 2009/1385 and 2014/0313).

Compliance with Ethical Standards

Conflict of Interests

VG, ADR, JM, and OM have no conflicts of interest to declare.

WFP declares receiving support from the following research grants: Abbott, Boehringer Ingelheim, Braincheck, CSL Behring, Daiichi-Sankyo, Immunarray, Janssen, Ortho Clinical Diagnostics, Portola, Relypsa, and Roche. He has served as a consultant in the following: Abbott, Astra-Zeneca, Bayer, Beckman, Boehringer-Ingelheim, Ischemia Care, Dx, Immunarray, Instrument Labs, Janssen, Nabriva, Ortho Clinical Diagnostics, Relypsa, Roche, Quidel, and Siemens. He provided expert testimony to Johnson and Johnson. He also has stock/ownership interests in the following: AseptiScope Inc., Brainbox Inc., Comprehensive Research Associates LLC, Emergencies in Medicine LLC, and Ischemia DX LLC.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    Gamero Donis D, Cebrián Patiño E, López C. Heart failure. Acute pulmonary oedema. In: Moya Mir MS, Piñera Salmerón P, Mariné Blanco M, editors. Tratado de Medicina de Urgencias, vol. Volumen 1. Madrid: Menarini. p. 516–31.Google Scholar
  2. 2.
    Cairns CB. Heart failure and pulmonary oedema. In: Tintinalli JE, Kelen GD, Stapczynski JS, editors. Medicina de urgencias. 6ª edit ed. Madrid: McGraw-Hill Interamericana de España; 2006. p. 425–9.Google Scholar
  3. 3.
    Hohman JS, Ingbar D. Cardiogenic shock and pulmonary oedema. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Harrison LJJ, editors. Principles of internal medicine. 3ª ed. Madrid: Elsevier; 2006. p. 185–90.Google Scholar
  4. 4.
    Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart. 2007;93:1137–46.Google Scholar
  5. 5.
    Redfield MM, Jacobsen SJ, Burnett JC, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289:194–202.Google Scholar
  6. 6.
    Bleumink GS, Knetsch AM, Sturkenboom MCJM, Straus SMJM, Hofman A, Deckers JW, et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure: The Rotterdam Study. Eur Heart J England. 2004;25:1614–9.Google Scholar
  7. 7.
    Ceia F, Fonseca C, Mota T, Morais H, Matias F, De Sousa A, et al. Prevalence of chronic heart failure in Southwestern Europe: the EPICA study. Eur J Heart Fail. 2002;4:531–9.Google Scholar
  8. 8.
    Formiga F, Chivite D. Acute heart failure: understanding the patient is essential. Emergencias. 2018;30:145–6.Google Scholar
  9. 9.
    Llorens P. Risk assessment in emergency department patients with acute heart failure: we need to reach beyond our clinical judgment. Emergencias. 2018;30:75–6.Google Scholar
  10. 10.
    García-Gutiérrez S, Quintana López JM, Antón-Ladislao A, Gallardo Rebollal MS, Rilo Miranda I, Morillas Bueno M, et al. External validity of a prognostic score for acute heart failure based on the Epidemiology of Acute heart failure in Emergency Departments registry: the EAHFE-3D scale. Emergencias. 2018;30:84–90.Google Scholar
  11. 11.
    Llauger L, Jacob J, Corominas Lasalle G, Puig Martorell J, González Casquet P, Bullon Chia A. Renal insufficiency and hyperkalemia in acute heart failure. Emergencias. 2018;30:357–8.Google Scholar
  12. 12.
    Carratala JM, Díaz Lobato S, Brouzet B, Más-Serrano P, Espinosa B, Llorens P. Efficacy and safety of high-flow nasal cannula oxygen therapy in patients with acute heart failure. Emergencias. 2018;30:395–9.Google Scholar
  13. 13.
    Harjola P, Harjola VP. Can we do more for patients with acute heart failure before arrival at the hospital? Emergencias. 2017;29:221–2.Google Scholar
  14. 14.
    Miró O, Llorens P, Escalada X, Herrero P, Jacob J, Gil V, et al. Prehospital emergency care of patients with acute heart failure in Spain: the SEMICA study (emergency medical response systems for patients with acute heart failure). Emergencias. 2017;29:223–30.Google Scholar
  15. 15.
    Viejo-Moreno R, Hernández-Corral J, Campos-Espolio MC. Comments on the SEMICA study (emergency medical response systems for patients with acute heart failure). Emergencias. 2017;29:429–30.Google Scholar
  16. 16.
    Gerber Y, Weston SA, Redfield MM, Chamberlain AM, Manemann SM, Jiang R, et al. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Intern Med. 2015;175:996–1004.Google Scholar
  17. 17.
    Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–9.Google Scholar
  18. 18.
    Martín-Sánchez FJ, Rodríguez-Adrada E, Vidan MT, Díez Villanueva P, Llopis García G, González Del Castillo J, et al. Impact of geriatric assessment variables on 30-day mortality among older patients with acute heart failure. Emergencias. 2018;30:149–55.Google Scholar
  19. 19.
    González-Colaço Harmand M, Prada Arrondo PC, Domínguez Rodríguez A. Quality of life for elderly patients with acute heart failure: is it time to talk? Emergencias. 2018;30:363.Google Scholar
  20. 20.
    Aguirre Tejedo A, Miró O. Precipitating factors in acute heart failure: a review. Emergencias. 2017;29:185–93.Google Scholar
  21. 21.
    Llorens P, Escoda R, Miró O, et al. Characteristics and clinical course of patients with acute heart failure and the therapeutic measures applied in Spanish emergency departments: based on the EAHFE registry (epidemiology of acute heart failure in emergency departments). Emergencias. 2015;27:11–22.Google Scholar
  22. 22.
    Llorens P, Miró O, Martín-Sánchez FJ, Herrero-Puente P, Jacob-Rodríguez J, Gil V, et al. Guidelines for emergency management of acute heart failure: consensus of the Acute Heart Failure Working group of the Spanish Society of Emergency Medicine (AHF-SEMES) in 2011. Emergencias. 2011;23:119–39.Google Scholar
  23. 23.
    Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;18(8):891–975.Google Scholar
  24. 24.
    Spinar J, Parenica J, Vitovec J, Widimsky P, Linhart A, Fedorco M, et al. Baseline characteristics and hospital mortality in the Acute Heart Failure Database (AHEAD) main registry. Crit Care. 2011;15:R291.Google Scholar
  25. 25.
    Chioncel O, Vinereanu D, Datcu M, Ionescu DD, Capalneanu R, Brukner I, et al. The Romanian Acute Heart Failure Syndromes (ROAHFS) registry. Am Heart J. 2011;162:142–53.Google Scholar
  26. 26.
    Follath F, Yilmaz MB, Delgado JF, Parissis JT, Porcher R, Gayat E, et al. Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). Intensive Care Med. 2011;37:619–26.Google Scholar
  27. 27.
    Oliva F, Mortara A, Cacciatore G, Chinaglia A, Di Lenarda A, Gorini M, et al. IN-HF outcome investigators. Acute heart failure patient profiles, management and in-hospital outcome: results of the Italian registry on heart failure outcome. Eur J Heart Fail. 2012;14:1208–17.Google Scholar
  28. 28.
    Tavazzi L, Maggioni A, Lucci J, Cacciatore G, Ansalone G, Oliva F, et al. Nationwide survey on acute heart failure in cardiology ward services in Italy. Eur Heart J. 2006;27:1207–15.Google Scholar
  29. 29.
    Logeart D, Isnard R, Resche-Rigon M, Seronde MF, de Groote P, Jondeau G, et al. Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study. Eur J Heart Fail. 2013;15:465–76.Google Scholar
  30. 30.
    Sosnowski MA. Review article: lack of effect of opiates in the treatment of acute cardiogenic pulmonary oedema. Emerg Med Australas. 2008;20(5):384–90.Google Scholar
  31. 31.
    Alison RC. Initial treatment of pulmonary edema: a physiological approach. Am J Med Sci. 1991;302(6):385–91.Google Scholar
  32. 32.
    Johnson MJ, McDonagh TA, Harkness A, McKay SE, Dargie HJ. Morphine for the relief of breathlessness in patients with chronic heart failure—a pilot study. Eur J Heart Fail. 2002;4(6):753–6.Google Scholar
  33. 33.
    Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2016;22(9):659–69.Google Scholar
  34. 34.
    Hoffman JR, Reynolds S. Comparison of nitroglycerin, morphine and furosemide in treatment of presumed pre-hospital pulmonary edema. Chest. 1987;92(4):586–93.Google Scholar
  35. 35.
    Sacchetti A, Ramoska E, Moakes ME, McDermott P, Moyer V. Effect of ED management on ICU use in acute pulmonary edema. Am J Emerg Med. 1999;17(6):571–4.Google Scholar
  36. 36.
    Gray A, Goodacre S, Seah M, Tilley S. Diuretic, opiate and nitrate use in severe acidotic acute cardiogenic pulmonary oedema: analysis from the 3CPO trial. QJM. 2010;103(8):573–81.Google Scholar
  37. 37.
    Peacock WF, Hollander JE, Diercks DB, Lopatin M, Fonarow G, Emerman CL. Morphine and outcomes in acute decompensated heart failure: an ADHERE analysis. Emerg Med J. 2008;25(4):205–9.Google Scholar
  38. 38.
    Iakobishvili Z, Cohen E, Garty M, Behar S, Shotan A, Sandach A, et al. Use of intravenous morphine for acute decompensated heart failure in patients with and without acute coronary syndromes. Acute Card Care. 2011;13(2):76–80.Google Scholar
  39. 39.
    Dominguez-Rodriguez A, Avanzas P, Burillo-Putze G, Abreu-Gonzalez P. Influence of morphine treatment on in-hospital mortality amog patients with acute heart failure. Med Intensiva. 2017;41(6):382–4.Google Scholar
  40. 40.
    Miró Ò, Gil V, Martín-Sánchez FJ, Herrero-Puente P, Jacob J, Mebazaa A, et al. Morphine use in the ED and outcomes of patients with acute heart failure: a propensity score-matching analysis based on the EAHFE registry. Chest. 2017;152(4):821–32.Google Scholar
  41. 41.
    Dominguez-Rodriguez A, Burillo-Putze G, Garcia-Saiz MDM, Aldea-Perona A, Harmand MG, Mirò O, et al. Study design and rationale of “a multicenter, open-labeled, randomized controlled trial comparing MIdazolam versus MOrphine in acute pulmonary edema”: MIMO trial. Cardiovasc Drugs Ther. 2017;31(2):209–13.Google Scholar
  42. 42.
    Domínguez-Rodríguez A, Abreu-González P. Morphine for acute pulmonary edema? Emergencias. 2016;28:418–20.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Víctor Gil
    • 1
    Email author
  • Alberto Domínguez-Rodríguez
    • 2
  • Josep Masip
    • 3
    • 4
    • 5
  • W. Frank Peacock
    • 5
    • 6
  • Òscar Miró
    • 1
    • 4
    • 5
  1. 1.Emergency Department, Hospital ClinicInstitut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  2. 2.Cardiology DepartmentHospital Universitario de CanariasTenerifeSpain
  3. 3.Cardiology DepartmentHospital TeknonBarcelonaSpain
  4. 4.University of BarcelonaBarcelonaSpain
  5. 5.GREAT NetworkRomeItaly
  6. 6.Department of Emergency MedicineBaylor College of MedicineHoustonUSA

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