Magnesium sulfate for the treatment of eclampsia: a brief review

Abstract

Background and purpose: Magnesium sulfate is used extensively for prevention of eclamptic seizures. Empirical and clinical evidence supports the effectiveness of magnesium sulfate; however, questions remain as to its safety and mechanism. This review summarizes current evidence supporting the possible mechanisms of action and several controversies for magnesium sulfate treatment.

Summary of review: Several mechanisms are presented, including the effects of magnesium sulfate on peripheral and cerebral vasodilation, blood-brain barrier protection, and as an anticonvulsant.

Conclusions: Though the specific mechanisms of action remain unclear, the effect of magnesium sulfate in the prevention of eclampsia is likely multi-factorial. Magnesium sulfate may act as a vasodilator, with actions in the peripheral vasculature or the cerebrovasculature, to decrease peripheral vascular resistance or relieve vasoconstriction. Additionally, magnesium sulfate may also protect the blood-brain barrier and limit cerebral edema formation, or it may act through a central anticonvulsant action.

Figures

Figure 1. Vascular Effects of Magnesium Sulfate

Magnesium is a potent vasodilator of uterine and mesenteric arteries, and aorta, but has minimal effect on cerebral arteries. In vascular smooth muscle, magnesium competes with calcium for binding sites, in this case for voltage-operated calcium channels (VOCC). Decreased calcium channel activity lowers intracellular calcium, causing relaxation and vasodilation. In endothelium, magnesium has been shown to increase production of prostaglandin I2 (through unknown mechanisms), which in turn decreases platelet aggregation. Magnesium also increases NO production causing vasodilation.

Figure 2. Effect of Magnesium Sulfate on Cerebral Edema and the Blood-brain Barrier

The calcium antagonistic effects of magnesium can also affect the cerebral endothelium that forms the blood-brain barrier. Decreased cell calcium inhibits endothelial contraction and opening of tight junctions that are linked to the actin cytoskeleton. Decreased tight junction permeability limits paracellular transport of vascular contents, ions and proteins, which can promote vasogenic edema and seizures. It is also possible that magnesium sulfate diminishes transcellular transport by limiting pinocytosis that is known to occur rapidly during acute hypertension. Magnesium may also downregulate aquaporin 4 (AQP4), a water channel protein localized to astrocytic endfeet, and possibly cerebral endothelium, that is associated with cerebral edema formation (through unknown mechanisms).

Figure 3. Anticonvulsant Activity of Magnesium Sulfate

Seizures consist of an excessive release of excitotoxic neurotransmitters including glutamate. Excessive glutamate can activate the N-methyl-d-aspartate (NMDA) receptor, leading to massive depolarization of neuronal networks and bursts of action potentials. Magnesium may act to increase the seizure threshold by inhibiting NMDA receptors, thereby limiting the effect of glutamate.