A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. A safer and more effective treatment regimen for eclampsia. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Expectant management in severe preeclampsia: does magnesium sulfate prevent the development of eclampsia? Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. [Anticonvulsant treatment in severe preeclampsia. Comparison between diazepam and magnesium sulfate]. Efficacy of magnesium sulphate and phenytoin in the management of eclampsia.
To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclampsia in women with severe pre-eclampsia.
                Randomised controlled trial.
                A tertiary referral obstetric unit.
                Eight hundred and twenty-two women with severe pre-eclampsia requiring termination of pregnancy by induction of labour or caesarean section.
                The women were randomised to receive either placebo (saline) or magnesium sulphate intravenously. The investigators were blinded to the contents of the pre-mixed solutions.
                The occurrence of eclampsia in the two groups.
                The data of 699 women were evaluated. Fourteen were withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of 345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95% confidence interval 0.01-0.69; P = 0.003).
                The use of intravenous magnesium sulphate in the management of women with severe pre-eclampsia significantly reduced the development of eclampsia. In a prospective controlled trial 91 consecutive women with eclampsia were randomly allocated either to a magnesium sulphate and nifedipine regime or to a lytic cocktail and nifedipine group. The type and severity of disease, details of labour and delivery, and the maternal and perinatal outcomes and complications related to the 2 treatment regimens were compared. Recurrence of fits, aspiration pneumonia and sudden hypotension were significantly reduced when patients were treated with the new magnesium sulphate and nifedipine regimen compared with the lytic cocktail plus nifedipine regimen. No patient treated with the new regimen died or had respiratory depression; in the other group there were 2 maternal deaths plus 1 case of severe hypoxic brain damage. No difference was observed in duration of labour or mode of delivery. Perinatal mortality was significantly lower in the magnesium sulphate plus nifedipine treated group. The synergistic action of magnesium sulphate and nifedipine in the dosage employed in this study may be used to reduce maternal and perinatal mortality and morbidity in women with eclampsia. Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.
                Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat.
                Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89).
                Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term. Although magnesium sulfate has been traditional or standard treatment for severe preeclampsia and eclampsia to prevent convulsions, its efficiency has always been in doubt and its induced side-effects also make it controversial for use. In this study, 64 patients, diagnosed with severe preeclampsia, were randomized into group I (34 patients) managed with MgSO4, and group II (30 patients) managed without MgSO4. There were no occurrences of eclampsia in either group. Although there was no statistical significance in the final delivery method, group I had a higher rate in cesarean section, in which most were significantly due to fetal distress (p < 0.05). Furthermore, group I had significantly more babies with poor apgar score than group II (p = 0.019). During the treatment period for those with a gestational age of less than 34 weeks, there were two patients with abruptio placentae in group I and the treatment periods were noted to be longer in group II than in group I. From the results of monitoring serum magnesium level in group I, when therapeutic level was achieved, magnesium sulfate induced great discomfort which might have led to the deterioration of the patients' condition. According to this study, magnesium sulfate's minimal efficiency, and its adverse side-effects, also make magnesium sulfate a poor choice in the management of preeclampsia. Therefore, because of our poor understanding of the etiology of preeclampsia, suitable management should be undertaken without magnesium sulfate. Improvement of the patient's pathophysiological condition or termination of pregnancy as early as possible, is recommended. This randomized controlled trial compared the use of magnesium sulphate with diazepam as anticonvulsant in 51 eclamptic women. The use of magnesium sulphate was associated with less serious morbidity (in terms of recurrence of convulsions, cardiopulmonary problems, disseminated intravascular coagulopathy, and acute renal failure) but the difference was not statistically significant (relative risk 0.6; 95% CI 0.3 to 1.2). The one maternal death occurred in the magnesium sulphate group. Convulsions recurred in five (21%) women in the magnesium sulphate group and seven (26%) women in the diazepam group. Urine output poor enough to prompt diuretic stimulation was less frequent in the magnesium sulphate group than in the diazepam group (RR 0.3; 95% CI 0.1 to 0.9). Significantly fewer infants born in the magnesium sulphate group had low Apgar scores (less than 7 at 1 min) compared with those in the diazepam group (RR 0.6; 95% CI 0.4 to 0.9). There were two early neonatal deaths in the magnesium sulphate group, and three stillbirths in the diazepam group. This study suggests that magnesium sulphate has advantages over diazepam for the mother and the infant in the treatment of eclampsia, but the trial is small and should be replicated on a larger scale. Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality. Although it is standard practice to use an anticonvulsant for management of eclampsia, the choice of agent is controversial and there has been little properly controlled evidence to support any of the options. 1687 women with eclampsia were recruited into an international multicentre randomised trial comparing standard anticonvulsant regimens. Primary measures of outcome were recurrence of convulsions and maternal death. Data are available for 1680 (99.6%) women: 453 allocated magnesium sulphate versus 452 allocated diazepam, and 388 allocated magnesium sulphate versus 387 allocated phenytoin. Most women (99%) received the anticonvulsant that they had been allocated. Women allocated magnesium sulphate had a 52% lower risk of recurrent convulsions (95% CI 64% to 37% reduction) than those allocated diazepam (60 [13.2%] vs 126 [27.9%]; ie, 14.7 [SD 2.6] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was non-significantly lower among women allocated magnesium sulphate. There were no significant differences in other measures of serious maternal morbidity, or in perinatal morbidity or mortality. Women allocated magnesium sulphate had a 67% lower risk of recurrent convulsions (95% CI 79% to 47% reduction) than those allocated phenytoin (22 [5.7%] vs 66 [17.1%] ie, 11.4 [SD 2.2] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was nonsignificantly lower among women allocated magnesium sulphate. Women allocated magnesium sulphate were also less likely to be ventilated, to develop pneumonia, and to be admitted to intensive care facilities than those allocated phenytoin. The babies of women who had been allocated magnesium sulphate before delivery were significantly less likely to be intubated at the place of delivery, and to be admitted to a special care nursery, than the babies of mothers who had been allocated phenytoin. There is now compelling evidence in favour of magnesium sulphate, rather than diazepam or phenytoin, for the treatment of eclampsia. Magnesium sulfate is used widely to prevent eclamptic seizures in pregnant women with hypertension, but few studies have compared the efficacy of magnesium sulfate with that of other drugs. Anticonvulsant prophylaxis with phenytoin for eclampsia has been recommended, but there are virtually no data to support its efficacy. Our objective was to compare magnesium sulfate with phenytoin in preventing seizures in hypertensive women during labor.
                We randomly assigned women with hypertension who were admitted for delivery to receive either magnesium sulfate or phenytoin. The magnesium sulfate regimen consisted of a 10-g intramuscular loading dose followed by a maintenance dose of 5 g given intramuscularly every four hours. For women with severe preeclampsia, an additional 4-g loading dose was given intravenously. The phenytoin regimen included a 1000-mg loading dose infused over a period of 1 hour, followed by a 500-mg oral dose 10 hours later. With either regimen, anticonvulsant therapy was continued for 24 hours post partum.
                Ten of 1089 women randomly assigned to the phenytoin regimen had eclamptic convulsions, as compared with none of 1049 women randomly assigned to magnesium sulfate (P = 0.004). There were no significant differences in any risk factors for eclampsia between the two study groups. Maternal and infant outcomes were also similar in the two study groups.
                Magnesium sulfate is superior to phenytoin for the prevention of eclampsia in hypertensive pregnant women. These results validate the long-practiced use of magnesium sulfate in the prevention of eclampsia. The objective was to compare the materno-fetal effects between Diazepam and Magnesium sulfate used as anticonvulsivant therapy in cases of severe pre-eclampsia. The study was prospective, comparative, longitudinal, randomized clinical trial. The study was done at Centro Medico Nacional Instituto Mexicano del Seguro Social. Division of Obstetrics and Gynecology, Torreon, Coah, Mexico. The patients were all the women admitted to the labor and delivery ward with diagnosis of severe pre-eclampsia and viable conceptus were assigned at random to receive either Diazepam (Group A, n = 19) or Magnesium sulfate (group B, n = 19). There were no significant differences between both groups. All of the patients remained alert, conscious and well oriented. None of the newborns showed hiporreflexia, flaccidity or neonatal respiratory distress that could be implicated to the anticonvulsivant therapy. It is concluded that Diazepam and Magnesium sulfate are good alternatives as anticonvulsivant therapy in cases of severe pre-eclampsia. Fifty pregnant women admitted with diagnosis of eclampsia were randomly allocated to magnesium sulphate (Group A) or phenytoin sodium (Group B) treatment group. Incidence of recurrence of seizures maternal as well as perinatal morbidity and mortality were compared in both the groups. Mean maternal age, parity and gestational age was similar in both the groups. Mean birth weight was significantly lower in Group B compared to Group A. Seizure frequency prior to hospitalization was 5.4 +/- 4.7 in Group A and 4.8-3.6 in Group B. Mean time interval between occurrence of first seizure and hospitalization was 9.6 +/- 3.5 hours in Group A and 11.8 +/- 9.3 hours in Group B, the difference was not statistically significant. Women treated with phenytoin had a higher incidence of recurrent seizures (10/25-40%) than those treated with magnesium sulphate (2/25-8%). Majority of the women treated with phenytoin (6/10-60%) had single convulsion after initiation of anticonvulsant therapy and 1 woman of each group had recurrent convulsions (75). There was no significant difference in perinatal outcome in both the groups. Maternal morbidity was comparable in both the groups and there was no maternal death in either of the groups.
Although strong evidence supports the use of magnesium sulphate for prevention and treatment of eclampsia, trials comparing alternative treatment regimens are too small for reliable conclusions.