Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial. A safer and more effective treatment regimen for eclampsia. Efficacy of magnesium sulphate and phenytoin in the management of eclampsia. A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. Magnesium sulphate versus diazepam in the management of eclampsia. Phenytoin sodium and magnesium sulphate in the management of eclampsia. Randomised study assessing the effect of phenytoin and magnesium sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound. Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality. Intravenous and intramuscular magnesium sulphate regimens in severe pre-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. 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. 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. 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. 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. 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. This clinical trial was conducted to compare the anticonvulsant response of magnesium sulphate and diazepam in the management of eclampsia. The study was carried out at the eclampsia unit of Dhaka Medical College Hospital during the period from October, 1995 to January, 1996. Two hundred consecutive admitted patients were recruited for the study and randomly assigned to two treatment groups: magnesium sulphate and diazepam. One hundred patients received injection magnesium sulphate and another one hundred received injection diazepam. All patients of both the group were matched for baseline characteristics. Convulsion was controlled in 95% of the patients of magnesium sulphate group and 74% of the patients of diazepam group (p < .0005). The mean controlling time is also significantly lower in magnesium sulphate group than diazepam group (8.50 hours vs 9.39 hours). Patients of magnesium sulphate group regain consciousness much earlier (mean time 20.62 hrs.) than the patients of diazepam group (mean time 40.62 hrs.). No significant difference was observed in controlling blood pressure and foetal outcome. The study finding shows that magnesium sulphate has some advantage over diazepam in controlling convulsion and regaining consciousness. If magnesium sulphate can be made available in the market by local production it may be recommended to use this drug in the primary health care without any hazzard before referring to other hospital. Twenty-two patients with eclampsia were randomly allocated to receive either intravenous phenytoin sodium or intravenous magnesium sulphate. The groups were comparable. No side-effects occurred and therapeutic levels were obtained in both groups. While none of the 11 patients managed with magnesium sulphate had further convulsions, four of the 11 treated with phenytoin sodium did and were subsequently effectively treated with magnesium sulphate. These results suggest that phenytoin sodium is not as effective an anticonvulsant in eclampsia as is magnesium sulphate. To assess maternal middle cerebral artery flow velocity patterns as measured by transcranial Doppler ultrasound (TCD) in eclampsia and to investigate the effect of the anticonvulsants magnesium sulphate (MgSO4) and phenytoin on cerebral circulation.
                Prospective randomised study.
                High care obstetric unit, King Edward VIII Hospital, Durban, South Africa.
                Twenty-four eclamptic patients: 13 received MgSO4 and 11 phenytoin.
                Middle cerebral artery flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the transtemporal approach in eclamptic patients, before and 15 minutes after the loading dose of anticonvulsant.
                Magnesium sulphate significantly reduced the pulsatility index (P = 0.002) and mean flow velocity (P = 0.02) in the middle cerebral artery, whereas phenytoin failed to produce any statistically significant effect. However, differences between groups were not statistically significant. Systolic and diastolic blood pressures were reduced in both the MgSO4 and phenytoin groups.
                These findings provide firm evidence that MgSO4 relieves cerebral vasospasm, compared with phenytoin, and may therefore be the better drug for the prevention of eclamptic convulsion. Two hundred patients with acute myocardial infarction were entered into a randomised double-blind trial where they received either intravenous magnesium sulphate or saline for 24 hours after admission to hospital. The incidence of ventricular arrhythmias necessitating treatment was reduced by more than half in the group receiving magnesium sulphate. There were two deaths in the group receiving magnesium sulphate and seven receiving saline placebo. Total cardiac events were significantly reduced in the magnesium treated group. These reductions cannot be attributed to differences in risk factors or therapy between the two groups, either before or during the period of study. These results suggest that magnesium administration reduces the incidence of serious tachyarrhythmias and death after acute myocardial infarction and that this simple regime warrants further study. Patients with severe pre-eclampsia were randomised to receive magnesium sulphate according to an intramuscular (IM) (N = 9) or an intravenous (i.v.) (N = 8) regimen. The IM regimen consisted of a loading dose of 14 g (4 g i.v. and 10 g IM) followed by 5 g 4-hourly. Patients given the IV regimen received a 6 g i.v. loading dose followed by a maintenance infusion of 2 g/h. Clinical outcome, laboratory parameters and serum magnesium levels were recorded for both groups. There were no significant differences between groups with regard to clinical outcome of either mother or child. Similar average serum magnesium concentrations were produced by the regimens the only significant difference was that fluctuations in magnesium levels were greater with the IM than the i.v. regimen. None of the patients had seizures despite levels mostly below 2 mmol/l.
Magnesium sulphate more than halves the risk of eclampsia, and probably reduces maternal death. There is no clear effect on outcome after discharge from hospital. A quarter of women report side effects with magnesium sulphate.