Washington University Emergency Medicine Journal Club– July 2023
Vingnette:
You’re working a typical shift in TCC one when encounter Mr. B, a 63-year-old male
with a history of hypertension, hyperlipidemia, and COPD. He presents with 3 days
of gradually worsening shortness of breath and cough productive of white sputum.
His shortness of breath has been minimally relieved by nebulized albuterol at home,
but has continued to worsen in spite of its use. He has been compliant with his
Spiriva and Advair.
On arrival to the ED, his oxygen saturation was 86% and is now improved to 93%
with 3 L of oxygen by nasal cannula (he is not on home oxygen). His lung sounds are
diminished with some faint wheezes and he is not in any distress, but does become
dyspneic when speaking.
You order the patient albuterol/atrovent duonebs, oral steroids, and azithromycin
for a presumed COPD exacerbation. His chest x-ray reveals hyper-expanded lungs
with no consolidation or infiltrates and his ECG is non-ischemic. Labs are normal
(aside from a chronically elevated bicarbonate level of 35) and his COVID test is
negative.
He has had some improvement in symptoms with treatment, but is still requiring
supplemental oxygen. You place an admit order to medicine for further management
and the medicine team calls and ask if you would given him some IV magnesium.
While well aware of the benefits of IV magnesium in acute asthma exacerbations,
you were not aware it was helpful for COPD. After ordering 2 grams of magnesium
sulfate, you decide to check the literature and see for yourself…
PICO Question
Population: Adults patients presenting to the ED with acute exacerbations of COPD
with no contraindication to IV magnesium infusion
Intervention: IV magnesium
Comparison: Standard or care or placebo
Outcome: Need for mechanical ventilation, need for hospital admission, need for
ICU admission, ED length of stay, hospital length of stay, mortality, and adverse
events
Search Strategy
A PubMed Clinical Queries search, using the terms “COPD magnesium” with the
“Therapy” filter and “Broad” scope, was performed, which resulted in 63 citations
(https://tinyurl.com/5n6jfx4v). Of these, three relevant randomized controlled
trials and one systematic review and meta-analysis were chosen for review
Article 1: Jahanian F, Khatir IG, Ahidashti HA, Amirifard S. The Effect of Intravenous
Magnesium Sulphate as an Adjuvant in the Treatment of Acute Exacerbations of
COPD in the Emergency Department: A Double-Blind Randomized Clinical Trial.
Ethiop J Health Sci. 2021 Mar;31(2):267-274. Answer Key.
Article 2: Vafadar Moradi E, Pishbin E, Habibzadeh SR, Talebi Doluee M, Soltanifar A.
The Adjunctive Effect of Intravenous Magnesium Sulfate in Acute Exacerbation of
Chronic Obstructive Pulmonary Disease: A Randomized Controlled Clinical Trial.
Acad Emerg Med. 2021 Mar;28(3):359-362. Answer Key.
Article 3: Ni H, Aye SZ, Naing C. Magnesium sulfate for acute exacerbations of
chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2022 May
26;5(5):CD013506. Answer Key.
Article 4: Skorodin MS, Tenholder MF, Yetter B, Owen KA, Waller RF, Khandelwahl S,
Maki K, Rohail T, D’Alfonso N. Magnesium sulfate in exacerbations of chronic
obstructive pulmonary disease. Arch Intern Med. 1995 Mar 13;155(5):496-500.
Answer Key.
Bottom Line
Intravenous infusions of magnesium sulfate have been used for years in the management of acute asthma exacerbations in both pediatric and adult patients. A Cochrane review from 2014 found that IV magnesium was associated with a reduction in the need for hospital admission and improved pulmonary function when used in the ED for adults with acute asthma exacerbations who failed to respond to other standard therapies (i.e. oxygen, inhaled beta-agonists, and corticosteroids). The use of IV magnesium for asthma in the ED is supported by ACEP policy “to supplement routine therapy in severe cases.” Its mechanism of action in asthma is primarily bronchodilation via smooth muscle relaxation (Spivey 1990), as well as some possible anti-inflammatory effects (Cairns 1996). While current guidelines do not mention the use of IV magnesium in management of acute exacerbation of COPD (AECOPD), the presence of significant overlap between COPD and asthma has led some to suggest a possible role in treatment. A 1995 randomized controlled trial conducted at 2 hospitals in the Veterans Affairs system (Skorodin 1995) found that administration of 1.2 grams of IV magnesium sulfate among 72 patients was associated with a significantly larger decease in peak expiratory flow at 30 and 45 minutes compared with placebo (25.1±35.7 L/min vs. 7.4±33.3 L/min; p = 0.03). There was no significant difference in changes in dyspnea score or maximum inspiratory or expiratory force; while there was a trend toward decreased hospital admission in the magnesium group (28.1% vs. 41.9%), this did not achieve statistical significance (p = 0.25). This study included almost entirely male patients and predated the routine use of inhaled ipratropium and systemic corticosteroids for AECOPD, which are now considered standard treatments (external validity). 3 Two single-center Iranian studies, published in 2021, have also evaluated the use of IV magnesium in AECOPD in a randomized, controlled fashion. The first of these (Jahanian 2021) included 60 patients randomized 1:1 to receive 2 grams of IV magnesium sulfate or normal saline alone. At 45 minutes (T2) and 6 hours after the intervention (T3), there was no significant difference in changes in FEV1, oxygen saturation, Borg scores, respiratory rate, or pulse rate between the two groups. Unfortunately, this study did not assess more patient-centered outcomes, such as need for hospital admission, need for mechanical ventilation, or length of stay. The second study from Iran (Vafadar 2021) included 77 patients, of whom 39 received magnesium sulfate (2.5 mg in 50 mL of saline) and 38 received normal saline. The primary outcome was change in respiratory rate (RR), dyspnea severity score (DSS), oxygen saturation (SpO2), and peak expiratory flow rate (PEFR) thirty minutes after a third nebulized treatment (60 minutes after initiation of study treatment). While there was no significant difference in the change in SpO2 between groups, the change in mean PEFR was larger in the magnesium group (15.67 vs. 5.03, p < 0.001), as were mean changes in DSS (-3.69 vs. -2.05, p < 0.001) and mean change in RR (-7.74 vs. -6.84, p = 0.045), although these later two differences do not appear to be clinically significant. A greater proportion of patients in the magnesium group were discharged home, but this difference did not achieve statistical significance (64.1% vs. 42.1%; OR 2.45, 95% CI 0.98 to 6.14). These studies are limited primarily by the use of surrogate outcomes and by small sample sizes. There was a trend toward decreased need for hospitalizationIn in the two studies in which this was measured, although neither study was sufficiently powered to demonstrate statistical significance. This latter finding highlights the importance of the subsequent systematic review and meta-analysis conducted by the Cochrane Collaboration (Ni 2022). This review identified 11 trials, of which 10 trials comprising 762 total participants were included in the quantitative synthesis. Among 3 studies reporting hospital admission rates (n = 170), IV magnesium was associated with a reduction in the need for hospitalization (OR 0.45, 95% CI 0.23-0.88; I2 = 0%). The associated number needed to treat (NNT) to prevent one admission was 7. There was also a reduction in hospital length of stay associated with IV magnesium (mean difference -2.7 days, 95% CI -4.73 to -0.66; I2 = 0%). There was no significant difference in need for noninvasive ventilation (n = 52) and none of the studies measured ED length of stay or all-cause mortality. Two studies reported adverse events, with none observed in the magnesium groups. While the authors of this meta-analysis conclude that the certainty of evidence for their findings was either low (hospital admission, inpatient length of stay) or very low (need for noninvasive ventilation or intubation) based on the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria, this represents the best evidence on this clinical question to date. Given that the associated risks of administering IV magnesium to patients without impaired renal function appears to be very low, it is reasonable to consider administering IV magnesium for patients presenting to the ED with AECOPD, in addition to standard treatment with oxygen, short-acting nebulized beta agonists, and systemic steroids