Elsevier

American Heart Journal

Volume 176, June 2016, Pages 114-121
American Heart Journal

Curriculum in Cardiology
The on- and off-target effects of morphine in acute coronary syndrome: A narrative review

https://doi.org/10.1016/j.ahj.2016.04.004Get rights and content

With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, morphine is the analgesic mainstay for patients with nitrate resistant chest pain due to acute Myocardial Infarction (MI). However, observational data suggest that morphine administration during MI may have negative consequences. While vomiting, hypotension and respiratory depression are established side effects, recent reports have demonstrated attenuated and delayed oral anti-platelet agent absorption, as well as suboptimal reperfusion after MI, all of which may translate into adverse cardiovascular outcomes. These data have resulted in reduced support for morphine in recent European and U.S. clinical practice guidelines for MI; despite the absence of any prospective randomized outcomes trials addressing this question. As such, randomized trials are now necessary to confirm whether or not morphine, which is administered in up to 30% of MI cases, causes adverse clinical outcomes in these patients. However, given that placebo-controlled randomized trial designs evaluating morphine in MI are limited by an ethical requirement for appropriate analgesia, alternative investigational approaches may be necessary. In this article we review the updated evidence for morphine in MI and outline novel strategies that may facilitate future investigation of this clinical dilemma.

Section snippets

STEMI guidelines (Table I)

The 2013 ACCF/AHA guidelines state that ‘In the absence of a history of hypersensitivity, morphine sulfate is the drug of choice for pain relief in patients with ST-segment elevation MI (STEMI)’, as, ‘it can alleviate the work of breathing, reduce anxiety, and favourably affect ventricular loading conditions’.4 However, the ACCF/AHA STEMI guideline provides no formal class of recommendation (COR) or level of evidence (LOE) designation.

According to the latest ECS guidelines for the management of

Pharmacologic considerations

Derived from the flowering poppy plant, Papaver somniferum, opioids have been used as analgesics for centuries. In the modern era, the pharmacology of endogenous opiates and opiate receptor systems was established in a number of elegant experiments on rodents and other mammals performed in the 1970s.11, 12, 13 All opiate receptors demonstrate considerable structural homology both with one another and with other G-protein coupled receptors.14 Opiate drugs exert their analgesic effects at

Analgesia

Chest pain is the most frequent presenting complaint in acute MI.17 A relationship between the duration of the pain and infarct size has been hypothesized. However, in the individual patient, one cannot predict the size of the infarction from the severity of the pain.18, 19 Theoretically, pain, via sympathetic nervous system activation, can increase myocardial oxygen demand and subsequently infarct size. Therefore pain control in ACS is of critical importance.

There are few head-to-head trials

Nausea and vomiting

Nausea and vomiting are common side effects of morphine. Studies have shown vomiting can occur in up to 15% of patients who are administered morphine compared to 2% in those who do not receive the medication in the setting of acute MI.9 The emetogenic effects of opioids are thought to occur through multiple mechanisms but principally by direct stimulation of the chemoreceptor trigger zone (CTZ), inhibition of gut motility, and stimulation of the vestibular apparatus.26, 27 Opioid’s inhibition

Future implications

Despite the enormous burden of ACS in western civilisations and the data described above, there is a dearth of prospective outcomes research on the optimal analgesic strategy for pain relief in MI. However, the design of the necessary randomized placebo control trials is substantially hindered by the ethical requirement for adequate analgesia. While the recently reported IMPRESSION trial was the first randomized placebo controlled study to assess morphine in this context, it lacked power to

Conclusion

Morphine remains the mainstay analgesic for severe chest pain in MI. Clinicians should be aware of emerging concerns regarding morphine administration in ACS, namely the adverse effect on gastrointestinal absorption of oral antiplatelet agents and the potential for increases adverse outcomes demonstrated in observational data. While morphine should be used where necessary, we believe that, pending the necessary randomized trials, this agent should be reserved only for ACS patients with chest

Acknowledgements

The authors report that they have nothing to disclose. No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents

References (55)

  • E.A. Amsterdam et al.

    Aha/acc guideline for the management of patients with non-st-elevation acute coronary syndromes: A report of the american college of cardiology/american heart association task force on practice guidelines

    J Am Coll Cardiol

    (2014)
  • P.T. O'Gara et al.

    Accf/aha guideline for the management of st-elevation myocardial infarction: Executive summary: A report of the american college of cardiology foundation/american heart association task force on practice guidelines

    Circulation

    (2013)
  • P.G. Steg et al.

    Esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation

    Eur Heart J

    (2012)
  • M. Roffi et al.

    2015 esc guidelines for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation: Task force for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation of the european society of cardiology (esc)

    Eur Heart J

    (2016)
  • E.L. Hobl et al.

    Morphine decreases clopidogrel concentrations and effects: A randomized, double blind, placebo-controlled trial

    J Am Coll Cardiol

    (2013)
  • G. Parodi et al.

    Morphine is associated with a delayed activity of oral antiplatelet agents in patients with st-elevation acute myocardial infarction undergoing primary pci

    Circ Cardiovasc Interv

    (2015)
  • S. de Waha et al.

    Intravenous morphine administration and reperfusion success in st-elevation myocardial infarction: Insights from cardiac magnetic resonance imaging

    Clin Res Cardiol

    (2015)
  • J.A. Lord et al.

    Endogenous opioid peptides: Multiple agonists and receptors

    Nature

    (1977)
  • W.R. Martin et al.

    Morphine physical dependence in the dog

    J Pharmacol Exp Ther

    (1974)
  • G.W. Pasternak

    Pharmacological mechanisms of opioid analgesics

    Clin Neuropharmacol

    (1993)
  • T.L. Yaksh

    Pharmacology and mechanisms of opioid analgesic activity

    Acta Anaesthesiol Scand

    (1997)
  • R.A. Shepher

    Neurotransmitters, anxiety and benzodiazepines: A behavioural review

    Neurosci Behav Rev

    (1986)
  • B.W. Karlson et al.

    Patients admitted to the emergency room with symptoms indicative of acute myocardial infarction

    J Intern Med

    (1991)
  • J. Herlitz et al.

    Enzymatically and electrocardiographically estimated infarct size in relation to pain in acute myocardial infarction

    Cardiology

    (1984)
  • B. Everts et al.

    A comparison of metoprolol and morphine in the treatment of chest pain in patients with suspected acute myocardial infarction--the memo study

    J Intern Med

    (1999)
  • J.R. Nielsen et al.

    Analgesic treatment in acute myocardial infarction. A controlled clinical comparison of morphine, nicomorphine and pethidine

    Acta Med Scand

    (1984)
  • J.J. Rouby et al.

    Hemodynamic and metabolic effects of morphine in the critically ill

    Circulation

    (1981)
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      Citation Excerpt :

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    The authors report that they have nothing to disclose.

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