A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT TRIAL OF INTRAVENOUS MAGNESIUM-SULFATE IN ACUTE STROKE

Background and Purpose Magnesium ions act as endogenous vasodilators o f the cerebral circulation and act pharmacologically as noncompetitive antagonists of the N-methyl-D-aspartate receptor by virtue of their r ole as endogenous voltage-sensitive blockers of the ion channel. The p reclinical efficacy of magnesium has been demonstrated in standard mod els of stroke. Methods Sixty patients were randomized to magnesium sul fate (8 mmol IV over 15 minutes and 65 mmol over 24 hours) or placebo within 12 hours of clinically diagnosed middle cerebral artery stroke. Pulse, blood pressure, and serum magnesium levels were monitored. Pri mary outcome was death or significant functional impairment (Barthel I ndex score <60) at 3 months. Results Magnesium was well tolerated, wit h no significant adverse effects and no change in blood pressure or pu lse rate. Laboratory and electrocardiographic variables did not differ significantly between placebo- and magnesium-treated groups. Serum ma gnesium rose from 0.76 mmol/L to 1.42 mmol/L over 24 hours and remaine d significantly higher than in the placebo group at 48 hours. Thirty p ercent of magnesium-treated and 40% of placebo-treated patients were d ead or disabled (Barthel Index score <60) at 3 months (P=.42). There w as a decrease in the number of early deaths in the magnesium-treated g roup (P=.066, log-rank test). Conclusions Magnesium sulfate is well to lerated after acute stroke and has no deleterious hemodynamic effects at this dose. Further trials are required to determine efficacy.