Journal Logo

What to D.O.

What to D.O.

Steer Clear of Magnesium for COPD

Pescatore, Richard DO

doi: 10.1097/01.EEM.0000754796.51054.ab
    Figure
    Figure:
    COPD, magnesium, Dutch hypothesis
    Figure
    Figure

    Knowingly or not, we in emergency medicine tend to lean into the Dutch hypothesis, a 1960s postulate that asthma and COPD are part of a spectrum of common disease (chronic obstructive lung disease), and should be considered a single disease with common genetic origins. It's an approach that allows us to cognitively coordinate the management of obstructive pulmonary disease to some degree.

    Both patient populations universally receive the inhaled beta agonists and anticholinergics we reflexively call for as well as a hefty dose of corticosteroids and a call to the respiratory therapist to initiate bi-level positive airway ventilation. Nebs. Steroids. BiPAP.

    But growing clinical experience understands these conditions as separate entities, which for all of their similarities uniting bronchoconstriction, bronchorrhea, and hypoventilation, have marked differences in the pattern of inflammation that occurs in the respiratory tract, with different inflammatory cells recruited, different mediators produced, distinct consequences of inflammation, and, importantly, differing responses to further therapy. (Breathe. 2011;7:229; https://bit.ly/3dja1VQ.) These pathophysiological differences underscore an important divergence in the treatment algorithm of obstructive pulmonary diseases—the use of magnesium.

    Possibility of Harm

    Magnesium has become somewhat of a darling in emergency medicine over the past few years. It has long been used for obstetric emergencies, but the medication has found growing use as an adjunct for treating headaches (Am J Emerg Med. 2021;39:28; https://bit.ly/3adOf4a), cardiac emergencies (Acad Emerg Med. 2019;26[2]:183; https://bit.ly/3mQpH65), and, of course, asthma, where use in severe cases has been shown to decrease hospitalization and improve peak expiratory flow. (Cochrane Database Syst Rev. 2000[2]:CD001490.) No data, however, support using magnesium to manage COPD exacerbations, and the real possibility of harm remains.

    Multiple randomized trials have undertaken the task of determining which effect, if any, magnesium may have in treating patients with acute exacerbations of COPD presenting to the emergency department. Some investigations have suggested mildly improved pulmonary function measures, but none has convincingly demonstrated a viable patient-oriented benefit to the medication's administration. Such discordance in therapeutic response demands skepticism about the Dutch hypothesis and recognition of the underlying pathophysiologic principles that drive a lack of benefit—and potential harm—from magnesium.

    The airway narrowing of asthma is predominantly due to contraction of airway smooth muscle as a result of multiple bronchoconstrictor mediators released from inflammatory cells, particularly mast cells. By contrast, the airflow limitation of COPD results from structural changes of small airways and closure of small airways as a result of disrupted alveolar attachments, resulting in air trapping and dyspnea. (Am J Respir Crit Care Med. 2006;174[3]:240; https://bit.ly/2PZwrCW.) The dominant pathology in asthma is mainly located in the larger conducting airways, while COPD predominantly affects the small airways and lung parenchyma.

    No Justification

    Recall that the purported reason for magnesium administration in asthma is calcium channel-mediated smooth muscle relaxation, leading to relief of bronchoconstriction and opening of the large airways. Given that COPD's smooth muscle pathophysiology principally targets smaller airways and alveoli, it's clear that a patient in extremis is unlikely to benefit from magnesium administration. The non-reversible airflow limitations of COPD could also potentially worsen as fibrotic distal airways are further incapacitated by hamstrung smooth muscle.

    Magnesium is often touted as a relatively cheap and benign intervention, but the reality is that its administration carries the real risk of harm, ranging from mild hypotension and flushing to pulmonary edema, not a good complication in a patient already in respiratory distress. Where physiologic benefit (large airway dilatation) cannot be found, only pathologic adversity remains.

    The Dutch hypothesis allows emergency physicians to approach life-threatening respiratory illness with a common set of tools and pathophysiologic principles. Rapid initiation of these resuscitative measures can make the difference in severe illness and significant distress. The addition of magnesium, however, represents a divergence from the Dutch hypothesis. Magnesium administration cannot be justified by the underlying structural causes of COPD and the available literature investigating its use.

    Dr. Pescatoreis the chief physician for the Delaware Division of Public Health and an emergency physician at Einstein Healthcare Network in Philadelphia. He is also the host with Ali Raja, MD, of the podcast EMN Live, which focuses on hot topics in emergency medicine:http://bit.ly/EMNLive. Follow him on Twitter@Rick_Pescatore, and read his past columns athttp://bit.ly/EMN-Pescatore.

    Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
    • kfrumkin10:15:58 AM<div></div><div>Dr. Pescatore, I have often appreciated your contributions to EMN. However, I take issue with your unsupported condemnation of magnesium for COPD. Even accepting your basic argument, “the absence of evidence is not evidence,” in my 36 years in both academic EM and busy community hospitals, I have used magnesium in COPD (which is rarely just COPD) and asthma probably thousands of times and never regretted it. Adding the times I’ve used it for other indications, the worst response I recall ever directly attributing to IV mag was some flushing. I never considered withholding it, and I’m convinced It helped me avoid intubation and admission on innumerable occasions. I recognize an appropriate academic skepticism of experience-based medicine. Yet my experience has always served my patients better than unreferenced opinion-based medicine from consultants and others. You offer no references. We can agree to disagree, but I hate to see magnesium’s use so strongly disparaged to such a wide audience without comment. In the absence of data, your opinion and advice to your many well-earned readers seem, objectively, to carry at least no more scientific weight than mine&#58; which has been, “Try it, you’ll like it!” and “We give it [in larger doses] to pregnant women.” </div><div><br></div><div>Best wishes, Ken Frumkin, PhD, MD</div><br>References&#58;<br>Skorodin, M. S., et al. (1995). Magnesium sulfate in exacerbations of chronic obstructive pulmonary disease. Arch Intern Med 155(5)&#58; 496-500. “CONCLUSION&#58; Magnesium sulfate, 1.2 g over 20 minutes after beta-agonist administration, is safe and modestly efficacious in the treatment of acute exacerbations of chronic obstructive pulmonary disease, and its bronchodilator effect is greater than that of a beta-agonist given alone and lasts beyond the period of magnesium sulfate administration.”<br><br>Shivanthan, M. C. and S. Rajapakse (2014). Magnesium for acute exacerbation of chronic obstructive pulmonary disease&#58; A systematic review of randomised trials. Ann Thorac Med 9(2)&#58; 77-80 ““Magnesium sulphate given intravenously did not seem to have an immediate bronchodilatory effect; however it appears to potentiate the bronchodilatory effect of inhaled beta-2 agonists. Increase in peak expiratory flow rate (PEFR) at 30 and 45 min was greater in those who received magnesium sulphate compared to placebo (P = 0. 03)”<br><br>Vafadar Moradi, E., et al. (2021). &quot;The Adjunctive Effect of Intravenous Magnesium Sulfate in Acute Exacerbation of Chronic Obstructive Pulmonary Disease&#58; A Randomized Controlled Clinical Trial.&quot; Acad Emerg Med 28(3)&#58; 359-362. 167 patients were screened and 77 were analyzed. . . &quot;The study group experienced significant improvement in PEFR, Dyspnea Severity Score, and RR. We did not observe any serious adverse events in either groups. None of the enrolled subjects required intubation. . . a greater [but non-significant] proportion of patients were discharged from ED in the Mg group (64. 1%) compared to the control group (42. 1%;)<br><br>Mukerji, S., et al. (2015). &quot;Intravenous magnesium sulphate as an adjuvant therapy in acute exacerbations of chronic obstructive pulmonary disease&#58; a single centre, randomised, double-blinded, parallel group, placebo-controlled trial&#58; a pilot study.&quot; N Z Med J 128(1425)&#58; 34-42. “17 patients were given saline, and 13 received 2 g of magnesium sulphate intravenously. . . Greater improvements were seen in FEV1 at T0, T60 and T120 compared to TB [std rx] in magnesium group (at T120, mean percentage change in FEV1 was 27.07% with magnesium versus 11.39% in the placebo group, 95%CI 3.7 to 27.7, p=0.01). Similar significantly greater improvements were noted with FVC in the magnesium group”<br><br>