A Safer and More Effective Treatment Regimen for Eclampsia

Summary: 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 signficantly 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.     

Maternal and perinatal outcome of eclampsia over a decade at a tertiary hospital in Kuwait

Aims: To determine maternal and perinatal outcome of eclampsia patients over a decade.

Methods: Analysis of case records of all eclampsia cases from January 2005 to December 2014.

Results: There were 30 cases of eclampsia. The most significant risk factors for developing pre-eclampsia are unbooked cases (97%), nulliparity, young age, marriage?≤4 months, history of pre-eclampsia in previous pregnancy, remarriage, preexisting diabetes mellitus, interval between pregnancies?≥10 years, positive family history. The incidence of eclampsia was 0.05%, antepartum eclampsia 15 (50%), intrapartum 6 (20%) and postpartum 9 (30%) with no maternal deaths, and 1 perinatal death. Perinatal mortality was 33.3/1000. 22 (73%) patients received magnesium sulphate (MgSO₄) and 8 patients (27%) received Diazepam, of which 1 had recurrence of convulsions. All 15 antepartum cases were delivered by cesarean section as were 2 intrapartum. 13 (43%) of women delivered vaginally. Only 6 (20%) patients were of low socio-economic status and were primary school educated. Severe maternal complications occurred in 8 (27%), with abruptio placentae being the most common 3 (38%).

Conclusions: Incidence of eclampsia was low, with no maternal deaths. MgSO4 was found to be highly effective. Lack of antenatal care is a major risk factor.     

Efficacy of magnesium sulphate and phenytoin in the management 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 sulphate in the treatment of eclampsia and pre-eclampsia: an overview of the evidence from randomised trials

Objective To evaluate the effectiveness of magnesium sulphate in the treatment of eclampsia and pre-eclampsia by a systematic quantitative overview of controlled clinical trials.
Design Online searching of the MEDLINE database between 1966 and 1995, and scanning of the bibliography of known primary studies and review articles on the use of magnesium sulphate in eclampsia and pre-eclampsia. Study selection, study quality assessment and data extraction were performed independently by two reviewers under masked conditions. Where possible outcome data from trials were pooled and summarised using the Mantel-Haenszel method.
Participants One thousand seven hundred and forty-three women with eclampsia and 2390 with pre-eclampsia included in nine randomised trials that evaluated the effects of magnesium sulphate.
Main outcome measures Seizure activity and maternal death.
Results In eclampsia, recurrence of seizures was less common with magnesium sulphate therapy compared with phenytoin (odds ratio [OR] 0.27, 95% CI 0.17.0.45,   P = 0.00  ) and diazepam (OR 0–41, 95% CI 0.30–0.57,   P = 0.00  ). As indicated by the point estimate, there was a trend towards a reduction in maternal mortality with magnesium sulphate in eclampsia (OR 0.51,95% CI 0.24–1.07,   P = 0.10  versus phenytoin; OR 0.78, 95% CI 0.41–1.45,   P = 0.52  versus diazepam). When used for seizure prophylaxis in pre-eclampsia, magnesium sulphate was found to be more effective than phenytoin (OR 0.15, 95% CI 0.03–0.72,   P = 0.01  ).
Conclusion Magnesium sulphate is a superior drug in preventing the recurrence of seizures in eclampsia and in seizure prophylaxis in pre-eclampsia.     

Preeclampsia into eclampsia: toward a new paradigm

OBJECTIVE: This study was undertaken to characterize aspects of the natural history of eclampsia.Study Design: A retrospective analysis was performed on the records of patients with eclampsia who were delivered at two tertiary care hospitals. RESULTS: Fifty-three pregnancies complicated by eclampsia were identified. Thirty-seven of the women were nulliparous. The mean age was 22 years (range, 15-38 years). Mean gestational age at the time of seizures was 34.2 weeks' gestation (range, 22-43 weeks' gestation). Twenty-eight women had antepartum seizures (53%); 23 of the 28 had seizures at home. Nineteen women had intrapartum seizures (36%). Eight of these women had seizures while receiving magnesium sulfate, and 7 had therapeutic magnesium levels. Six women had postpartum seizures (11%), 4 >24 hours after delivery. Headache preceded seizures in 34 cases. Visual disturbance preceded seizures in 16 cases. The uric acid level was elevated to >6 mg/dL in 43 women. There were no maternal deaths or permanent morbidities. There were 4 perinatal deaths. Two patients had intrauterine fetal deaths at 28 and 36 weeks' gestation. These mothers had seizures at home. One infant died of complications of prematurity at 22 weeks' gestation and one died of respiratory complications at 26 weeks' gestation. There were 4 cases of abruptio placentae, 1 of which resulted in fetal death. Of the 53 cases of eclampsia, only 9 were potentially preventable. One of these was that of a woman who was being observed at home. The other 8 women were hospitalized and had hypertension and proteinuria. Only 7 women could be considered to have severe preeclampsia before seizure (13%), and 4 of these 7 women were receiving magnesium sulfate. CONCLUSIONS: Eclampsia was not found to be a progression from severe preeclampsia. In 32 of 53 cases (60%) seizures were the first signs of preeclampsia. In this series eclampsia appeared to be more of a subset of preeclampsia. Only 9 cases of eclampsia were potentially preventable with current standards of practice. Our paradigm for this disease, as well as our approach to seizure prophylaxis, should be reevaluated.     

Magnesium sulphate for the management of preeclampsia

In case of eclampsia, and especially in case of preeclampsia, no consensus exist in order to treat or to prevent convulsions by routine use of magnesium sulphate, at least in France. However, a large, multicentre, randomised trial compared the efficacy of magnesium sulphate with diazepam or phenytoin in eclamptic women. In this trial, magnesium sulphate was associated with a significantly lower rate of recurrent seizures and lower rate of maternal death than that observed with other anticonvulsants. The primary objective of magnesium sulphate prophylaxis in women with preeclampsia is to prevent or reduce the rate of eclampsia and complications associated with eclampsia. There are 3 large randomised controlled trials comparing the use of magnesium sulphate to prevent convulsions in patients with severe preeclampsia: the first one was vs phenytoin, the second vs placebo, and the third vs nimodipine. Patients receiving magnesium sulphate presented a significant lower risk of eclampsia than that observed with other comparison groups, probably by decreasing the cerebral perfusion pressure, thus avoiding a cerebral barotrauma. However, several arguments balance a wide use of magnesium sulphate: the prevalence of eclampsia in the Western world is very low, the use of magnesium sulphate does not affect the neonatal morbidity and mortality, and it is associated with a high rate of side effects, sometimes severe, such as respiratory depression. Thus, the benefit to risk ratio has to guide the use of magnesium sulphate and is directly correlated to the prevalence of eclampsia according to the risk of considered group. 1) The rate of seizures in women with mild preeclampsia not receiving magnesium sulphate is very low. Magnesium sulphate may potentially be associated with a higher number of adverse maternal effects. Therefore, the benefit to risk ratio does not support routine use of magnesium sulphate prophylaxis in this group. 2) On the other hand, the higher rate of seizures in women with severe preeclampsia (2.0%), especially in those who have imminent eclampsia, justifies prophylaxis with magnesium sulphate.     

Neurological complications in eclampsia: a case series

OBJECTIVES: Neurological abnormalities contribute significantly to maternal mortality in eclampsia. We studied the epidemiology and neurological and obstetric outcome of such patients. METHODS: A retrospective analysis was done at a referral center. 19 cases of eclampsia with recurrent convulsions (n = 8) or coma without convulsions (n = 5) or cerebrovascular accidents (n = 4) or blindness (n = 2) were studied. We excluded cases with primary neurological abnormalities. Management included initial stabilization followed by early delivery. Primary anticonvulsant was magnesium sulphate. RESULTS: The incidence of eclampsia was 0.71%. Among 61 cases, 19 (31.14%) had neurological abnormalities; 15 patients had no antenatal care. Three cases were postpartum. Comatose patients had the highest mean arterial pressure (MAP) (mean 154.66 mm Hg, p = 0.027). Fundoscopy was usually normal. Computerized tomography revealed mild cerebral edema in six cases and accurately diagnosed all cerebrovascular accidents. Phenytoin controlled convulsions in 7/8 cases with recurrent seizures. The cesarean section rate was 37.5% and admission to delivery interval was 10.38 hours. Five perinatal and two maternal deaths were recorded among 19 cases. Neurological recovery was complete in all survivors. CONCLUSIONS: Critical care back-up is essential at tertiary referral centers for a large proportion of neurological abnormalities in eclampsia. High MAP and accompanying thrombocytopenia may be key factors in cerebral pathology. CT scan is a simple and effective investigation in these cases. Phenytoin is an effective second-line anticonvulsant. No maternal death was related directly to cesarean section. Early delivery prevents worsening of systemic status.     

Is the prophylactic administration of magnesium sulphate in women with pre-eclampsia indicated prior to labour?

Objective To determine whether prophylactic magnesium sulphate is necessary to prevent eclampsia and associated complications among women with pre-eclampsia prior to labour.
Design Case series.
Setting Tertiary referral centre.
Population Three hundred and eighteen women with pre-eclampsia (blood pressure > 140/90 mmHg and > 2+ proteinuria) who were not in labour or for planned induction thereof and had not received magnesium sulphate during transfer.
Methods Clinical evaluation of the pregnant women with careful blood pressure control. Magnesium sulphate was withheld even in the presence of imminent eclampsia. During labour, the option of magnesium sulphate prophylaxis was left to the clinician, but magnesium sulphate was administered in cases of eclampsia.
Main outcome measures Eclampsia and related complications.
Results Five women (1.5%) developed eclampsia, although none developed related complications. Women presented at an early gestational age (mean 30 weeks), with high blood pressure, often suffering from headaches. Twenty pregnancies were terminated prior to viability, of which half were terminated for maternal reasons. Ten intrauterine deaths occurred. Most often fetal distress (38.6%) initiated the delivery process, which was mainly by caesarean section (68.5%). With the exception of epigastric discomfort, symptoms and signs of imminent eclampsia decreased after admission. Blood pressure values were significantly lower at delivery although biochemistry results deteriorated from admission to delivery.
Conclusion In women with pre-eclampsia prior to labour, where blood pressure control was carefully applied but magnesium sulphate not given, the eclampsia rate was low and eclampsia did not appear to worsen the existing prognosis for mother or fetus.     

A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use

BackgroundEvidence from RCTs shows that magnesium sulfate reduces the risk of seizures and mortality for women with pre-eclampsia/eclampsia. However, it has been argued that outcomes within trials may not reflect real-world outcomes with the same intervention.ObjectiveTo assess whether outcomes for women with pre-eclampsia/eclampsia who received magnesium sulfate in the real world were comparable to those in RCTs.Search strategyEMBASE and MEDLINE were searched (January 1990–July 2010).Selection criteriaCohort, before-and-after, and serial cross-sectional studies were included. Participants were women with eclampsia who received magnesium sulfate or another anticonvulsant, and women with pre-eclampsia who received magnesium sulfate or no anticonvulsant. Primary outcomes were death (maternal, fetal, neonatal) or recurrent seizures.Data collection and analysisData were extracted independently by 2 reviewers.Main resultsSix studies (1831 women with eclampsia) were included, from academic centers in Bangladesh, India, Pakistan, and Nigeria, together with 2 population-based UK studies. Magnesium sulfate for eclampsia was associated with lower risks of maternal death, recurrent seizure, and major morbidity; for pre-eclampsia, it was associated with lower risks of eclampsia.ConclusionImprovements in maternal outcome with magnesium sulfate for pre-eclampsia/eclampsia in real-world use are comparable to those reported in RCTs.     

Severe pre-eclampsia and eclampsia in Abha, the south west region of Saudi Arabia.

A retrospective study was conducted over a 10-year period on 32,000 maternities at Abha General Hospital, Abha, Saudi Arabia, to estimate the contribution of eclampsia and severe pre-eclampsia to maternal mortality and morbidity and also fetal wastage. It included 18 cases of eclampsia and 297 cases of severe pre-eclampsia. Multiple regression analysis revealed that only the presence of prodromal symptoms significantly affected the occurrence of eclampsia, p < 0.05, while nulliparous patients were a high risk group for eclampsia. Maternal complications including eight cases of massive ascites occurred exclusively in severe pre-eclamptics. Although no maternal deaths were reported, the perinatal mortality rate was 16.6% and 14.1% among the eclamptics and severe pre-eclamptic patients, mainly from prematurity. Regarding the eclamptic patients, 17(94.4%) had the first fit before arrival at the hospital, 13(72.2%) before labour, while 3(16.6%) had fits before and during labour and 1(5.6%) had the fits after delivery. Suggestions are proffered to reducing maternal morbidity and perinatal mortality and morbidity.     

Maternal and fetal outcome in eclamptic patients in Benin City, Nigeria.

Eclampsia is a well-recognised major cause of maternal death and perinatal morbidity and mortality. The incidence of eclampsia, its presentation patterns, maternal and perinatal outcomes were investigated in a retrospective study conducted at the University of Benin Teaching Hospital, Nigeria over an 8-year period, 1995 - 2002. There were 103 cases of eclampsia of 7835 deliveries, giving an incidence of one in 76 (1.32%). The mean age of the women was 27.1 +/- 5.6 years. Eclampsia significantly (P < 0.001) occurred in nulliparous and unbooked mothers. Eighty-nine (86.4%) of the patients developed fits in the predelivery stage; 85 (83%) of the patients had at least one premonitory symptom including headache (82.4%) visual disturbance (10.6%) and epigastric pain (7%). There were nine stillbirths and 16 early neonatal deaths for a perinatal mortality rate of 214/1000. The major causes of perinatal mortality were prematurity and birth asphyxia. Eleven maternal deaths occurred with a maternal case fatality rate of 10.7% and a maternal mortality ratio from eclampsia of 140/100 000. The clinical causes of deaths were cardiopulmonary failure, acute renal failure, haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome and cerebrovascular accident. Timely referral of high-risk patients coupled with availability of emergency obstetric and neonatal care services would reduce the incidence eclampsia associated mortality and morbidity in our facility.     

Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials

In the US, the routine use of magnesium sulfate for seizure prophylaxis in women with preeclampsia is an ingrained obstetric practice. During the past decade, several observational studies and randomized trials have described the use of various regimens of magnesium sulfate to prevent or reduce the rate of seizures and complications in women with preeclampsia. There are only 2 double-blind, placebo-controlled trials evaluating the use of magnesium sulfate in mild preeclampsia. There were no instances of eclampsia among 181 women assigned to placebo, and there were no differences in the percentage of women who progressed to severe preeclampsia (12.5% in magnesium group vs 13.8% in the placebo group, relative risk [RR] 0.90; 95% CI 0.52-1.54). However, the number of women enrolled in these trials is too limited to draw any valid conclusions. There are 4 randomized controlled trials that compare the use of no magnesium sulfate, or a placebo vs magnesium sulfate, to prevent convulsions in patients with severe preeclampsia. The rate of eclampsia was 0.6% among 6343 patients assigned to magnesium sulfate vs 2.0 % among 6330 patients assigned to a placebo or control (RR 0.39; 95% CI 0.28-0.55). However, the reduction in the rate of eclampsia was not associated with a significant benefit in either maternal or perinatal outcome. In addition, there was a higher rate of maternal respiratory depression among those assigned magnesium sulfate (RR 2.06; 95% CI 1.33-3.18). The evidence to date confirms the efficacy of magnesium sulfate in reduction of seizures in women with eclampsia and severe preeclampsia; however, this benefit does not affect overall maternal and perinatal mortality and morbidities. The evidence regarding the benefit-to-risk ratio of magnesium sulfate prophylaxis in mild preeclampsia remains uncertain, and does not justify its routine use for that purpose.     

Maternal and perinatal outcome of eclampsia in tertiary health institution in Southeast Nigeria

Objective: To evaluate the maternal and perinatal outcome in patients with eclampsia at Nnamdi-Azikiwe-University-Teaching-Hospital (NAUTH), Nnewi, Nigeria. Methods: A retrospective study of cases of eclampsia managed at NAUTH over a 10 year period – 1st January, 2000 to 31st December, 2009. Maternal outcome was measured in terms of complications and maternal death. Foetal outcome was assessed in terms of low birth weight, pre-term births, low apgar score, and perinatal deaths. Results: There were 57 cases of eclampsia out of a total of 6,262 deliveries within the study period, giving a prevalence of 0.91%. Majority, 71.7%, had caesarean section. There were 17.4% maternal deaths mainly from pulmonary oedema, 6 (13.0%), acute renal failure, 4 (8.7%), and coagulopathy, 3 (6.5%). Perinatal deaths were 25.5% as a result of prematurity, 42 (82.4%), and low birth weight, 36 (70.6%). Twenty-one (41.2%) of the new born had Apgar score of less than seven at 5?min while 13.0% were severely asphyxiated. Conclusion: Eclampsia was associated with high maternal and perinatal morbidity and mortality in this study. There is need to review existing protocol on eclampsia management with emphasis on appropriate health education of pregnant mothers, good antenatal care, early diagnosis of pre-eclampsia with prompt treatment.     

Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial

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.     

Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial

Summary. 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% CI0.3 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 (<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.     

Management of eclampsia at Assiut University Hospital, Egypt

ObjectiveTo evaluate the protocol used for management of eclampsia at Assiut University Hospital, Assiut, Egypt.MethodsIn a prospective cross-sectional study, data were collected from 1998 women treated for eclampsia at Assiut University Hospital between January 1990 and January 2010, including 1594 cases of prepartum eclampsia, 75 of intrapartum eclampsia, 16 of intercurrent eclampsia, and 313 of postpartum eclampsia. The treatment regimen included use of nifedipine as an antihypertensive, magnesium sulfate as an anticonvulsant, rapid interruption of pregnancy, and admission to the ICU. Data were evaluated for control of blood pressure, prevention and control of convulsions, and maternal and perinatal outcomes.ResultsMagnesium sulfate was effective in controlling convulsions in 98.1% of women. Nifedipine initiated a smooth decline in blood pressure (P > 0.0001). There were 79 maternal deaths (3.95%). Maternal morbidity occurred in 439 (22%) women. Twenty-seven percent of women delivered vaginally (most of these women were admitted postpartum). Perinatal mortality occurred in 7.9% of cases.ConclusionA combination of nifedipine as an antihypertensive drug, magnesium sulfate as an anticonvulsant, rapid interruption of pregnancy, and managing the patients in the ICU resulted in a marked improvement in the outcome for both mother and fetus at Assiut University Hospital.     

Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women with gestational hypertension

OBJECTIVE: To describe the incidence of eclampsia in women with mild gestational hypertension when only women with severe gestational hypertension are given magnesium sulfate prophylaxis. METHODS: This is a prospective 4(1/2)-year observational study. Those women who met our criteria for severe gestational hypertension received intravenous magnesium sulfate prophylaxis, and women with nonsevere hypertension did not. Data were collected at delivery to ascertain the incidence of eclampsia and maternal and neonatal morbidity. RESULTS: A total of 72,004 women were delivered during the study period, 6,431 had gestational hypertension, 3,935 met the criteria for severe disease and were given magnesium sulfate prophylaxis, 2,496 women with nonsevere hypertension were not treated. Eighty-seven women developed eclampsia, for an overall incidence of 1 in 828 deliveries, a 50% increase when compared with 5 preceding years where all women with gestational hypertension were given magnesium sulfate prophylaxis. Of the 2,496 women with nonsevere hypertension who were not treated, 27 had eclampsia (1 in 92). Women with eclampsia were more likely to require general anesthesia for cesarean delivery compared with hypertensive women without eclampsia (23% versus 4%, P < .001), but they had no additional morbidity. Infants of eclamptic mothers had more adverse outcomes than those without convulsions (12% versus 1%, P < .04). CONCLUSION: Selective magnesium sulfate prophylaxis results in an increased overall incidence of eclampsia because of more seizures in women with nonsevere gestational hypertension who are not given magnesium sulfate prophylaxis. LEVEL OF EVIDENCE: II-3.