Discussion
The FAST-MAG phase 3 trial did not confirm the primary hypothesis that prehospital initiation of magnesium sulfate in patients with a suspected stroke during the hyperacute phase would reduce the level of disability at 90 days. There was no significant difference in mortality, and the overall number of serious adverse events was similar in the magnesium group and the placebo group. The study achieved its systems aim of delivering the study agent to patients with stroke faster than in previous phase 3 trials, with nearly three quarters of the patients treated in the “golden hour,” the first 60 minutes after the onset of stroke.20
There are several potential explanations for the neutral results with respect to magnesium sulfate. Magnesium trafficking across the blood–brain barrier is not immediate. The concentration of magnesium in the cerebrospinal fluid peaks 4 hours after parenteral administration in the presence of an intact blood–brain barrier and more quickly in regions of focal ischemia where the blood–brain barrier is disrupted.9 Magnesium sulfate may not have accumulated in brain tissues quickly enough to yield a benefit despite rapid attainment of increased serum levels. In addition, a single neuroprotective agent may not interdict enough pathways in the molecular elaboration of ischemic injury, and combinations of agents or agents with highly pleiotropic effects may be required.