Magnesium Sulfate Cuts Eclampsia Risk
The study involved about 10,000 women hospitalized with preeclampsia. Half of them were randomly assigned to receive magnesium sulfate, and the others were given a placebo. Forty women in the magnesium sulfate group and 96 in the placebo group had an eclamptic convulsion during the study. The 58-percent reduction in the risk for eclampsia translated into 11 fewer cases of the pregnancy complication per 1,000 women.
Compared with placebo, magnesium sulfate therapy seemed to lower the risk for placental abruption. In all, abruptio placentae occurred in 90 women in the magnesium sulfate group and 141 in the placebo group. The risk reduction corresponded to 12 fewer cases of placental abruption per 1,000 women.
A report describing the study appears in the June 1 Lancet.
Women who participated in the studydubbed the Magnesium Sulphate for Prevention of Eclampsia, or MAGPIE, trialwere recruited from 175 hospitals in 33 countries. Eligible participants were pregnant or had given birth within 24 hours of enrollment and had two or more diastolic blood-pressure readings of at least 90 mm Hg or systolic blood-pressure readings of at least 140 mm Hg.
Another eligibility requirement was that "clinical uncertainty" existed about whether magnesium sulfate would benefit the patient. According to the research team, this requirement reduced the recruitment of women with severe preeclampsia from countries where the disorder is commonly treated with magnesium sulfate. In countries where magnesium sulfate is not the standard of care for the treatment of severe preeclampsia, women with the condition were available to participate in the study.
Identical-appearing magnesium sulfate and placebo treatment packs were prepared by an independent supply company and allocated to the clinical sites. Magnesium sulfate was supplied in 10-mL ampules, each containing 5 g of magnesium sulfate heptahydrate at a concentration of 2 mmoL of magnesium per milliliter. Each ampule of placebo contained 10 mL of normal saline.
In most cases, treatment consisted of an 8-mL loading dose of magnesium sulfate or placebo diluted in 0.9 percent sodium chloride injection and delivered intravenously for 1015 minutes. For maintenance therapy, diluted drug or placebo was infused intravenously for 24 hours at 2 mL (1 g) per hour.
Study sites were also given the option to administer the maintenance doses as intramuscular injections, a practice used at facilities in 15 countries. According to the report, reasons to choose the intramuscular route probably included cost, safety, and the availability of trained staff. The risks of eclampsia and neonatal death were higher at these facilities than at study centers where the treatment was administered intravenously, but intramuscular magnesium sulfate still outperformed placebo.
Half of the study participants in each treatment group were discharged from the hospital by day six. Follow-up data were collected for each patient until discharge from the hospital.
The research team reported that 317 women in the magnesium sulfate group and 118 in the placebo group asked to stop treatment early or stopped taking the study medication because of adverse events. Adverse effects associated with magnesium sulfate treatment included flushing, nausea, vomiting, and muscle weakness. Twenty-four percent of the women in the magnesium sulfate group and 4 percent of the women who received placebo had at least one adverse event during the study.
Eleven women in the magnesium sulfate group and 20 in the placebo group died during the study, representing a 45-percent reduction in the risk of death for women treated with magnesium sulfate.
A commentary in the same issue of Lancet urged international organizations to use the study findings to promote the use of magnesium sulfate for preventing eclampsia in women at risk for the complication. The commentators pointed out that the drug's cost$5 or less per patientmakes the treatment feasible even in developing countries.