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;26:183; 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: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;174:240; 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.
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.