Magnesium Concentration in Cerebrospinal and Brain Interstitial Fluid Correlates with Serum Level in Induced Hypermagnesemia

Kajetan L Von Eckardstein,Veit Rohde,Jürgen C W Kiwit,Ulf Westhause

doi:10.4236/ojmn.2016.62015

Kajetan L Von Eckardstein, Veit Rohde + Show 2 more

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https://doi.org/10.4236/ojmn.2016.62015

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Abstract

Being a modulator of the N-methyl-D-aspartate (NMDA) receptor function magnesium has been studied for its neuroprotective and vasodilatative properties in acute and delayed brain ischemia due to vasospasm in aneurysmal subarachnoid haemorrhage (aSAH) and stroke. A number of clinical phase II and III studies have correlated serum magnesium concentrations after intravenous continuous application to clinical outcome and have failed to show a positive therapeutic effect. However, no study supported its conclusion by providing evidence for a local increase in magnesium, i.e. in the cerebrospinal fluid (CSF) and the brain parenchyma. The objective of our observational study was to compare magnesium levels in serum, CSF, and brain microdialysis samples (MDS) in patients with aSAH. Seventeen patients with aSAH at World Federation of Neurosurgeons (WFNS) grade IV and V were included. According to our internal standard treatment protocols, all patients received a ventricular catheter, a frontal intracerebral microdialysis probe, and a continuous intravenous application of 80 mmol MgSO4 per 24 hours. Magnesium concentrations of serum, CSF, and MDS were recorded. We found a positive and significant correlation of increased serum levels of magnesium to CSF and MDS magnesium concentrations. These pharmacokinetic findings may serve as a basis for further discussion of the concept of induced hypermagnesemia in patients with aSAH, especially in the context of recent level A evidence of the lack of clinical benefit.

Highlights

Interest in magnesium as a neuroprotectant and antivasospastic agent for the therapy in cerebral aneurysmal subarachnoid haemorrhage and stroke, and in perinatal hypoxia, has risen over the last couple of years, but declined after publication of a phase III international multicenter placebo controlled trial (MASH-2) [1] and a meta-analysis [2] in 2012, both concluding that prophylactic intravenous magnesium does not improve neurological outcome in patients with aSAH
Patients with Magnesium Application We identified 17 (6 male/11 female) consecutive patients with a World Federation of Neurosurgeons (WFNS) grade IV (8 patients) and V (9 patients) aSAH who received a standard ventricular drain, a frontal implantation of a microdialysis probe, and an intravenous continuous magnesium application
We were able to show that a continuous intravenous application of magnesium sulphate does result in an increase of [Mg2+]cerebrospinal fluid (CSF) and [Mg2+]microdialysis samples (MDS), the latter presumably representing an increase of [Mg2+]ecf

Summary

Introduction

Interest in magnesium as a neuroprotectant and antivasospastic agent for the therapy in cerebral aneurysmal subarachnoid haemorrhage (aSAH) and stroke, and in perinatal hypoxia, has risen over the last couple of years, but declined after publication of a phase III international multicenter placebo controlled trial (MASH-2) [1] and a meta-analysis [2] in 2012, both concluding that prophylactic intravenous magnesium does not improve neurological outcome in patients with aSAH. Since the first description of reversal of delayed cerebral vasospasm by magnesium in rats [3] and a pilot study on the management of patients with a Fisher Grade 3 aSAH [4], numerous case studies [5] and larger dose finding clinical study [6] were published, partially with good and promising clinical outcomes [7]. An animal study on transient focal cerebral ischemia in rats concluded that a serum magnesium level between 2.0 and 3.0 mmol/L offered best protection [8]. The rational of magnesium application for the treatment of cerebral vasospasm and stroke is mainly based upon the voltage-dependent blockage of the N-methyl-D-aspartate (NMDA) receptor [9] which effects cellular energy metabolism, vascular tone, and cell membrane transport [10]. Magnesium causes vasodilatation by stimulation of endothelial prostacyclin release and prevents vasoconstriction by a variety of mediators [11]

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