Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: current status

Delayed ischemic neurological deficit or clinical vasospasm remained a major cause for delayed neurological morbidity and mortality for patients with aneurysmal subarachnoid hemorrhage (SAH). Magnesium is a cerebral vasodilator. In experimental model of drug or SAH-induced vasospasm, magnesium blocks voltage-dependent calcium channels and reverses cerebral vasoconstriction. Furthermore, its antagonistic action on N-methyl-D-aspartate receptor in the brain prevents glutamate stimulation and decreases calcium influx during ischemic injury. Clinically, the protective effect of magnesium has also been found useful in women with preeclampsia, a condition thought to be due to cerebral vasospasm. Initial experimental result in human was found to safe and effective as compared to historical data. In our pilot study, 60 patients were randomly allocated to receive either magnesium sulfate infusion 80 mmol/day or saline infusion for 14 days. The incidence of symptomatic vasospasm decreased from 13/30(43%) in the saline group to 7/30(23%) in the patients receiving magnesium sulfate infusion, p = 0.10, odds ratio 0.398, 95% CI 0.131-1.211. Favorable outcome (Good recovery and moderate disability, as defined by Glasgow Outcome Scale) was achieved in 20 of 30 (67%) patients receiving magnesium sulfate infusion and 16 of 30 (53%) patients receiving placebo treatment, p = 0.292, odds ratio 1.750, 95% CI 0.616-4.974.From literature review, a total of 441 patients from four studies (including ours) were grouped for analysis. Using random effects model (Mantel-Haenszel, Robins-Breslow-Greenland), the pooled odds ratio for symptomatic vasospasm or delayed cerebral ischemia is, 0.620, 95% CI 0.389-0.987, statistically significant. Similarly, the pooled odds ratio for favorable outcome is 1.598, 95% CI 1.074-2.377, statistically significant. There are two multi-center phase III studies (IMASH and MASH2) being carried out to assess the clinical effects, in which IMASH has finished data collection on 30th June 2009.