OBJECT: Vasospasm remains a significant source of neurological morbidity and 
mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances 
in current medical, surgical, and endovascular therapies. Magnesium sulfate 
therapy has been demonstrated to be both safe and effective in preventing 
neurological complications in obstetrical patients with eclampsia. Evidence 
obtained using experimental models of brain injury, cerebral ischemia, and SAH 
indicate that Mg may also have a role as a neuroprotective agent. The authors 
hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on 
vasospasm and, ultimately, on neurological outcome following aneurysmal SAH.
METHODS: A prospective randomized single-blind clinical trial of high-dose MgSO4 
therapy following aneurysmal SAH (Hunt and Hess Grades II-IV) was performed in 
40 patients, who were enrolled within 72 hours following SAH and given 
intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were 
maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical 
management principles were the same between groups (including early use of 
surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis 
and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings 
were obtained, and clinical outcomes were measured using the Glasgow Outcome 
Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using 
the independent t-test. Forty patients were enrolled in the study: 20 (15 female 
and five male patients) received treatment and 20 (11 female and nine male 
patients) comprised a control group. The mean ages of the patients in these 
groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades 
were 2.6 +/- 0.68 in the MgSO4 treatment group and 2.3 +/- 0.73 in the control 
group (mean +/- standard deviation [SD], p = 0.87). Fisher grades were similar 
in both groups. Mean middle cerebral artery velocities were 93 +/- 27 cm/second 
in MgSO4-treated patients and 102 +/- 34 cm/second in the control group (mean 
+/- SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in 
six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. 
Mean GOS scores were 3.8 +/- 1.6 and 3.6 +/- 1.5 (mean +/- SD, p = 0.74) in the 
treatment and control groups, respectively. Significant adverse effects from 
treatment with MgSO4 did not occur.
CONCLUSIONS: Administration of high-dose MgSO4 following aneurysmal SAH is safe, 
and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. 
This treatment does not interfere with neurological assessment, administration 
of anesthesia during surgery, or other aspects of clinical care. We observed a 
trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in 
the group treated with MgSO4, but the trend did not reach a statistically 
significant level. A larger study is needed to evaluate this trend further.