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Magnesium Sulfate in Eclampsia and Pre-Eclampsia

Pharmacokinetic Principles

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Abstract

Magnesium sulfate (MgSC4) is the agent most commonly used for treatment of eclampsia and prophylaxis of eclampsia in patients with severe pre-eclampsia. It is usually given by either the intramuscular or intravenous routes. The intramuscular regimen is most commonly a 4g intravenous loading dose, immediately followed by 10g intramuscularly and then by 5g intramuscularly every 4 hours in alternating buttocks. The intravenous regimen is given as a 4g dose, followed by a maintenance infusion of 1 to 2 g/h by controlled infusion pump.

After administration, about 40% of plasma magnesium is protein bound. The unbound magnesium ion diffuses into the extravascular-extracellular space, into bone, and across the placenta and fetal membranes and into the fetus and amniotic fluid. In pregnant women, apparent volumes of distribution usually reach constant values between the third and fourth hours after administration, and range from 0.250 to 0.442 L/kg. Magnesium is almost exclusively excreted in the urine, with 90% of the dose excreted during the first 24 hours after an intravenous infusion of MgSO4. The pharmacokinetic profile of MgSO4 after intravenous administration can be described by a 2-compartment model with a rapid distribution (α) phase, followed by a relative slow β phase of elimination.

The clinical effect and toxicity of MgSO4 can be linked to its concentration in plasma. A concentration of 1.8 to 3.0 mmol/L has been suggested for treatment of eclamptic convulsions. The actual magnesium dose and concentration needed for prophylaxis has never been estimated. Maternal toxicity is rare when MgSO4is carefully administered and monitored. The first warning of impending toxicity in the mother is loss of the patellar reflex at plasma concentrations between 3.5 and 5 mmol/L. Respiratory paralysis occurs at 5 to 6.5 mmol/L. Cardiac conduction is altered at greater than 7.5 mmol/L, and cardiac arrest can be expected when concentrations of magnesium exceed 12.5 mmol/L. Careful attention to the monitoring guidelines can prevent toxicity. Deep tendon reflexes, respiratory rate, urine output and serum concentrations are the most commonly followed variables.

In this review, we will outline the currently available knowledge of the pharmacokinetics of MgSO4 and its clinical usage for women with pre-eclampsia and eclampsia.

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Acknowledgements

The authors would like to thank Xiaomei Cao and Jinqiu Xu for their assistance in preparing the manuscript, and Dr Cyprian O. Onyeji for his review.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Jingling Hospital, Nanjing P.R., China

    Jian F. Lu

  2. Pharmacy Research, Hartford Hospital, Hartford, Connecticut, USA

    Jian F. Lu & Charles H. Nightingale

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  1. Jian F. Lu
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  2. Charles H. Nightingale
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Correspondence to Jian F. Lu.

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Lu, J.F., Nightingale, C.H. Magnesium Sulfate in Eclampsia and Pre-Eclampsia. Clin Pharmacokinet 38, 305–314 (2000). https://doi.org/10.2165/00003088-200038040-00002

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