DOSE OPTIMIZATION OF INTRAVENOUS MAGNESIUM-SULFATE AFTER ACUTE STROKE

Background and Purpose-Parenterally administered MgSO4 is neuroprotect ive in standard animal models of focal cerebral ischemia and in many o ther paradigms of brain injury. Previous small clinical trials in stro ke patients have explored the safety and tolerability of different inf usion regimens. This study was undertaken to optimize the regimen for a multicenter trial. Methods-Within 24 hours of the onset of clinicall y diagnosed stroke, patients were randomized to receive placebo or one of three intravenous MgSO4 infusions: a loading infusion of 8, 12, or 16 mmol, followed by 65 mmol over 24 hours. Cardiovascular parameters , serum magnesium concentrations, and blood glucose concentrations wer e determined. Outcome at 30 and 90 days was recorded. Results-Twenty-f ive patients were recruited and treated at a mean time of 20 hours aft er stroke. No tolerability problems were identified. No effects of mag nesium on heart rate, blood pressure, or blood glucose were evident. S erum magnesium concentrations rose to target levels most rapidly in th e highest loading infusion group and were maintained in all groups for at least 24 hours. Conclusions-MgSO4 infusions that rapidly elevate t he serum magnesium concentration to potentially therapeutic levels are well tolerated and have no major hemodynamic effects in patients with acute stroke. The 16-mmol loading infusion achieved target serum conc entrations most rapidly and has been chosen for further trials.