Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Efficacy of magnesium sulphate and phenytoin in the management of eclampsia. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. Randomised study assessing the effect of phenytoin and magnesium sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Phenytoin sodium and magnesium sulphate in the management of eclampsia. A safer and more effective treatment regimen for eclampsia. A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. Phenytoin versus magnesium sulfate in preeclampsia: a pilot study.
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. 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. 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. 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. 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. 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. 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. 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. A randomized clinical trial was designed to determine whether there are clinically demonstrable advantages of phenytoin over magnesium sulfate in preeclamptic patients because of the latter drug's uterine relaxant properties. An intravenous infusion, immediately after randomization, of either phenytoin or magnesium sulfate, with subsequent measurement of serum concentrations and maintenance of therapeutic levels was given to 103 preeclamptic and two eclamptic women. Observed were the rate of cervical dilation during active labor and change in hematocrit between predelivery and 24-hour postdelivery values and the incidence of side effects ascertained by interview. Compared with those receiving magnesium sulfate, patients receiving phenytoin had more rapid cervical dilation (3.3 cm/hr versus 1.5 cm/hr, p = 0.016) and a smaller fall in hematocrit after delivery (-4.7% versus -7.6%, p = 0.034). A significantly lower incidence of hot flushes (15% versus 46%, p < 0.005) and a trend toward less dyspnea and weakness were reported by phenytoin-treated patients. Our phenytoin regimen produced acceptable serum phenytoin levels (10 to 25 micrograms/ml) in 96% of patients.
Magnesium sulphate, rather than phenytoin, for women with eclampsia reduces the risk ratio of recurrence of seizures, probably reduces the risk of maternal death, and improves outcome for the baby. Magnesium sulphate is the drug of choice for women with eclampsia. The use of phenytoin should be abandoned.