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Magnesium for Aneurysmal Subarachnoid Haemorrhage (MASH-2): A Randomized Placebo-Controlled Trial
Study Question: Is there an improved clinical outcome with the use of intravenous magnesium sulfate in patients with aneurysmal subarachnoid haemorrhage?
Methods: This was a three phase randomized, multi-center, placebo-controlled trial. Adult patients admitted to a neurological or neurosurgical ICU within 4 days of haemorrhage and a diagnosis of aneurysmal subarachnoid haemorrhage were included. Patients were randomized to magnesium sulfate therapy or placebo (blinded) by a computer generated code. Those receiving magnesium sulfate therapy were administered a regimen of 64 mMol/day IV over 24 hours for 20 days after haemorrhage onset, until hospital discharge, or death, whichever occurred sooner. Local treatment protocols were used which included nimodipine 360 mg/day, aneurysm occlusion, bed rest, and normovolemia. The primary outcome was dependence (defined as Rankin Scale score of 4 or 5) or death, 3 months after haemorrhage.
Results: A total of 1204 patients were enrolled and randomized to magnesium (n=606) or placebo (n=597). Baseline data did not differ between the groups. Results showed no significant difference in the primary outcome, symptoms or mRankin Scale score between groups.
Conclusion: Based on the results of this trial, authors recommend against the routine use of IV magnesium (64 mMol/day) to prevent delayed cerebral ischemia following aneurysmal subarachnoid haemorrhage, due to lack of beneficial outcome.
Perspective: Magnesium has mechanisms of neuroprotection that are thought to help prevent delayed cerebral ischemia. However, as the authors note in discussion, this effect may not be adequate enough to overcome other complications of aneurysmal subarachnoid haemorrhage that play a role in outcome. Results of this study are consistent with other trial data that IV magnesium sulfate does not affect outcome after aneurysmal subarachnoid haemorrhage.