Magnesium sulfate in aneurysmal subarachnoid hemorrhage: a randomized controlled trial.
OBJECTIVE
Magnesium reverses cerebral vasospasm and reduces infarct volume after experimental subarachnoid hemorrhage (SAH) in rats. We aimed to assess whether magnesium reduces the frequency of delayed cerebral ischemia (DCI) in patients with aneurysmal SAH.


METHODS
Patients were randomized within 4 days after SAH. Magnesium sulfate therapy consisted of a continuous intravenous dose of 64 mmol/L per day, to be started within 4 days after SAH and continued until 14 days after occlusion of the aneurysm. The primary outcome DCI (defined as the occurrence of a new hypodense lesion on computed tomography compatible with clinical features of DCI) was analyzed according to the "on-treatment" principle. For the secondary outcome measures "poor outcome" (Rankin >3) and "excellent outcome" (Rankin 0), we used the "intention-to-treat" principle.


RESULTS
A total of 283 patients were randomized. Magnesium treatment reduced the risk of DCI by 34% (hazard ratio, 0.66; 95% CI, 0.38 to 1.14). After 3 months, the risk reduction for poor outcome was 23% (risk ratio, 0.77; 95% CI, 0.54 to 1.09). At that time, 18 patients in the treatment group and 6 in the placebo group had an excellent outcome (risk ratio, 3.4; 95% CI, 1.3 to 8.9).


CONCLUSIONS
This study suggests that magnesium reduces DCI and subsequent poor outcome, but the results are not yet definitive. A next step should be a phase III trial to confirm the beneficial effect of magnesium therapy, with poor outcome as primary outcome.
van den Bergh
Walter M
WM
Department of Neurology, Room G03.124 University Medical Center Utrecht, PO Box 85500 3508 GA Utrecht, The Netherlands. w.m.vandenbergh@neuro.azu.nl
Algra
A
A
van Kooten
F
F
Dirven
C M F
CM
van Gijn
J
J
Vermeulen
M
M
Rinkel
G J E
GJ
D002545:Brain Ischemia / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis / Q000188:drug therapy*
D008278:Magnesium Sulfate