Prehospital Use of Magnesium Sulfate as Neuroprotection in Acute Stroke

Jonathan Frazier, PharmD Candidate 2015 Mercer University College of

Pharmacy According to the Centers for Disease Control and Prevention (CDC), stroke is one of the leading causes of death in the United States, claiming nearly 130,000 lives each year.1 Unfortunately, studies show that not only are our current available therapies all reperfusion based, but they are also only moderately effective.2,3 It is believed that neuroprotection agents, such as magnesium sulfate, are promising treatment strategies that can be used complementary to reperfusion treatments. In this case, magnesium sulfate is thought to be effective in its abilities to produce vasodilation in systemic and pulmonary circulation by inhibiting calcium ion influx4 and by decreasing platelet aggregation and increasing bleeding time.5

Primary Outcome MeasureDegree of disability 90 days after a stroke as measured with the use of a modified Rankin scale.

Title: Prehospital Use of Magnesium Sulfate as Neuroprotection in Acute Stroke
Design Multicenter, randomized, double-blind, placebo-controlled; 1700 participants.
Objective Initiation of the neuroprotection agent magnesium sulfate by paramedics in the field would improve the long-term functional outcome of patients.
Study groups 1700 patients underwent randomization into two study groups: Magnesium sulfate: 857 patients Placebo: 843 patients
Methods Patients had to have a suspected stroke as determined with the use of the modified Los Angeles Prehospital Stroke Screen (LAPSS) and treatment initiation had to occur within two hours after the patient was last known to be free of stroke symptoms. Then patients were randomly assigned in a 1:1 ratio into either a study group (magnesium infusion) or placebo group. Magnesium sulfate: 4 g of magnesium sulfate in 54 ml of normal saline infused over 15 minutes followed by a maintenance infusion of 16 g of magnesium sulfate in 240 ml of normal saline infused over 24 hours. Concomitant stroke therapy followed national practice guidelines from the American Heart Association (AHA) and American Stroke Association (ASA).
Duration January 2005 through December 2012
Baseline Characteristics Magnesium (857): mean age 69+13, female sex 358 (41.8%), glucose level on arrival at hospital 133.7 mg/dl + 50.5 mg/dl, LAMS score before treatment* 3.7+1.3, medical history: hypertension 671 (78.3%), diabetes 189 (22.1%), hyperlipidemia 398 (46.4%), myocardial Infarction 94 (11%) Placebo (843): mean age 69+14, female sex 367 (43.5%), glucose level on arrival at hospital 136.5 mg/dl + 52.0 mg/dl, LAMS score before treatment* 3.7+1.3, medical history: hypertension 648 (76.9%), diabetes 188 (22.3%), hyperlipidemia 407 (48.3%), myocardial Infarction 82 (9.7%) * Scores on the Los Angeles Motor Scale (LAMS) range from 0 to 10, with higher scores indicating more severe motor weakness.
Results Modified Rankin scale levels: Level 0: Magnesium 18.7%, Placebo 18.4% Level 1: Magnesium 16.3%, Placebo 16.2% Level 2: Magnesium 18.4%, Placebo 18.3% Level 3: Magnesium 13.3%, Placebo 13.3% Level 4: Magnesium 10.5%, Placebo 10.6% Level 5: Magnesium 10.1%, Placebo 10.2% Level 6: Magnesium 12.7%, Placebo 13.0% P = 0.28 by the Cochran-Mantel-Haenszel test
Adverse Events Common Adverse Events:N/A
Serious Adverse Events:Magnesium: 439 (51.2%) patients reported adverse effects across all organ systems: blood and lymphatic system disorders 15 (1.8%), cardiac disorders 199 (13.9%), gastrointestinal disorders 59 (6.9%), infections and infestations 68 (7.9%), nervous system disorders 245 (28.6%), respiratory, thoracic and mediastinal disorders 68 (7.9%) and vascular disorders 92 (10.7%)
Percentage that Discontinued due to Adverse Evens:N/A
Study Author Conclusions Based on the findings of this study, the authors conclude that although magnesium sulfate therapy is safe and did not prevent the start of therapy within 2 hours after the onset of stroke symptoms, it did not improve disability outcomes at 90 days. Furthermore, there were no significant differences in mortality and the overall number of serious adverse events was similar in both the magnesium and placebo group.

Overall this study did not show positive results for magnesium as a neuroprotective agent. Neuroprotective agents are being studied in stoke management due to their potential to improve patient’s quality of life. The key to their success requires that they first and foremost be safe and beneficial, but that they can also be given within the first two hours of stroke symptoms without hindering imaging. Although magnesium sulfate did not show promising results, there are still other drug therapies undergoing testing.

References

1. http://www.cdc.gov. Stoke. 2015 Available at: http://www.cdc.gov/stroke/statistics_ maps.htm. Accessed February 27, 2015.
2. Adeoye O, Hornung R, Khatri P, et al. Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke 2011;42:1952-5.
3. Saver JL. Improving reperfusion therapy for acute ischaemic stroke. J Thromb Haemost 2011;9:Suppl 1:333-43.
4. Durlah J. Magnesium deficiency thrombus. Lancet 1967;1:1362.
5. Ramussen HS, Larsen OG, Meior K. Haemodynamic effects of intravenously administered magnesium sulphate in patients with ischaemic heart disease. Clin Cardiol 1998;11;824-8.
6. Saver JL, Starkman S, Eckstein M, et al. Prehospital use of magnesium sulfate as neuroprotection in acute stroke. N Engl J Med. 2015;372(6):528-36.

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