Magnesium sulphate: too much of a good thing?

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The use of magnesium sulphate for the prevention of eclampsia is now considered a universal practice in obstetrics. Still, which women require magnesium prophylaxis and which regimen to use remain elusive. Given the substantial knowledge gaps concerning the pharmacological properties of magnesium therapy, a number of dosing practices have been proposed over the past 50 years. Remarkably, a consistent regimen that has been proven to be both effective and safe has yet to be clearly defined. In the current article, Okusanya et al. provide a comprehensive and critical review of the numerous dosing regimens and resultant drug concentrations in the context of two landmark protocols—intravenous (Zuspan) and intramuscular (Pritchard). Despite marked heterogeneity of study design and variable reporting of pertinent pharmacokinetic results, the authors coherently summarise the anticipated serum magnesium concentrations when using any number of regimens. To summarise their findings, bioavailability for both intravenous and intramuscular regimens is rapid with overall diminished but more consistent steady-state levels for the intravenous regimen. From this point, they posit that magnesium may be efficacious, namely preventing a seizure, even at levels lower than previously thought necessary. We find their suggestion of moderation reminiscent of the Shakespearean comedy As You Like It, wherein Rosalind asks, ‘Can one desire too much of a good thing?’ We applaud the efforts of Okusanya et al. in sifting through the important, but oft-forgotten, literature upon which contemporary practices are now based; however, we find several important caveats regarding clinical efficacy to be considered while reviewing their analysis. First—and especially important because of the current obesity epidemic—little attention is given to the significance of maternal size and its effects on the volume of distribution and resultant serum magnesium levels. Tudela et al. (Obstet Gynecol 2013;121:314–20) studied more than 5300 women given magnesium prophylaxis and reported that maternal habitus had a significant effect on serum magnesium levels—indeed, over half of obese women had a serum level considered subtherapeutic 4 hours after a loading dose of 6 g. Second, clinical efficacy is difficult to define given the relative rarity of eclamptic events in treated women. Put another way, what defines efficacy—a measured serum level or prevention of an eclamptic event? An equally important consideration beyond efficacy is safety. It is imperative to remember two tenets of magnesium therapy, regardless of which regimen is administered. First, magnesium is cleared almost exclusively by renal excretion, so levels can be dangerously elevated in the setting of compromised glomerular filtration. Second, although it is uncontested that excessive magnesium sulphate can be toxic to the mother, the authors did not address any neonatal consequences (Abassi-Ghanavati et al. Am J Perinatol 2012; 29:795–800). As concluded by Okusanya et al., there are more questions to be answered concerning eclampsia prophylaxis using magnesium sulphate. We laud these investigators for their work in distilling more than 50 years of magnesium sulphate protocols into a comprehendible summary recognising that derivatives of these protocols now act as the underpinnings for contemporary practices. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.