The role of magnesium in the management of cerebral vasospasm.

Mitchell J Odom,J Mocco,Scott L Zuckerman

doi:10.1155/2013/943914

Abstract

Subarachnoid hemorrhage (SAH) is characterized by bleeding into the subarachnoid space, often caused by ruptured aneurysm. Aneurysmal rupture occurs in 700,000 individuals per year worldwide, with 40,000 cases taking place in the United States. Beyond the high mortality associated with SAH alone, morbidity and mortality are further increased with the occurrence of cerebral vasospasm, a pathologic constriction of blood vessels that can lead to delayed ischemic neurologic deficits (DIND). Treatment of cerebral vasospasm is a source of contention. One extensively studied therapy is Magnesium (Mg) as both a competitive antagonist of calcium at the N-methyl D-aspartate (NMDA) receptor, and a noncompetitive antagonist of both IP3 and voltage-gated calcium channels, leading to smooth muscle relaxation. In our literature review, several animal and human studies are summarized in addition to two Phase III trials assessing the use of intravenous Mg in the treatment of SAH (IMASH and MASH-2). Though many studies have shown promise for the use of Mg in SAH, there has been inconsistency in study design and outcomes. Furthermore, the results of the recently completed clinical trials have shown no significant benefit from using intravenous Mg as adjuvant therapy in the treatment of cerebral vasospasm.

Highlights

Subarachnoid hemorrhage (SAH) due to ruptured aneurysm occurs in 700,000 individuals a year [1], with nearly 40,000 of those cases occurring in the United States [2]
Despite having been recorded in patients treated for aneurysmal subarachnoid hemorrhage in 1951 [9], cerebral vasospasm (CVS) still remains a prevalent and morbid complication of SAH [10]
To identify the role of magnesium in animal models, we have summarized several studies in Table 1, demonstrating magnesium’s dilatory effects on vertebral arteries after established SAH and observed CVS

Summary

Introduction

Subarachnoid hemorrhage (SAH) due to ruptured aneurysm occurs in 700,000 individuals a year [1], with nearly 40,000 of those cases occurring in the United States [2]. In terms of a therapeutic role for magnesium in vasospasm, its function as a physiologic calcium antagonist and a potent vasodilator has been of most interest, though some neuroprotective effects have been observed [21,22,23,24]. The protection afforded to the neurovascular unit or to neuronal functioning is most likely due to the attenuation of the glutamate surge in a postischemic setting [29] This prevents a postischemia excitotoxic phase from occurring and preserves brain parenchyma from further harm. The goal of this review is to assess the current state of research regarding magnesium, its role as both a calcium antagonist and neuroprotective agent when used to treat cerebral vasospasm. These two domains will be the main focus of this review, as they provide the greatest wealth of data to direct future studies

Experimental Data

Clinical Data

Findings

Future Directions