Original Article
A Comparison of Magnesium Sulfate and Nimodipine for the Prevention of Eclampsia
N Engl J Med 2003; 348:304-311January 23, 2003
- Abstract
Objective
Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. Our objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia.
Methods
We conducted an unblinded, multicenter trial in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic–clonic seizure.
Results
Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001).
Conclusions
Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia.
Media in This Article
Table 1
Base-Line Characteristics of the Study Population.Table 2
Maternal Complications.Article Activity
- Article
Cerebral infarction and hemorrhage still account for the majority of deaths from eclampsia and preeclampsia.1,2 Preeclampsia causes regional vasoconstriction, and many believe that eclampsia results from cerebral vasospasm and resultant ischemia.3-6 Magnesium sulfate is generally accepted as the treatment of choice for eclampsia.7-9 The use of magnesium sulfate to prevent eclampsia has been common in the United States for decades10,11 but has not been internationally adopted. The placebo-controlled Magnesium Sulphate for Prevention of Eclampsia (MAGPIE) trial12 recently confirmed the prophylactic action of magnesium sulfate and is likely to increase the use of this agent in women with preeclampsia worldwide.
Since magnesium sulfate has a cerebral vasodilator effect,13 one explanation for its antieclamptic action is that it decreases ischemia by reducing cerebral vasospasm. We hypothesized that if eclampsia is caused by cerebral ischemia, nimodipine, a calcium-channel blocker that is a specific cerebral vasodilator,14,15 would be an ideal alternative drug. Potential advantages of nimodipine also include its oral route of administration, minimal toxicity, and antihypertensive effect. Therefore, we compared the efficacy of nimodipine with that of magnesium sulfate for the prevention of seizures in patients with severe preeclampsia.
Methods
We conducted an unblinded, randomized, controlled trial between 1995 and 2000. We enrolled women with severe preeclampsia at 14 sites in eight countries (see the Appendix). The protocol was approved by the local review board at each site. All patients provided written informed consent. Patients with severe preeclampsia in whom the decision had been made to effect delivery were eligible provided they had not already received magnesium sulfate and did not have a preexisting seizure disorder. The diagnostic criteria16 are described in detail in the Supplementary Appendix. Severe preeclampsia was defined as elevated blood pressure (at least 140/90 mm Hg) with proteinuria (a dipstick reading of 1+ or more) in association with one or more of the following: headache, clonus, visual disturbances, epigastric pain or pain in the right upper quadrant, oliguria (urinary output of less than 500 ml per 24 hours), pulmonary edema, elevated liver aminotransferase levels (an alanine aminotransferase or aspartate aminotransferase level of more than 40 U per liter), elevated creatinine level (at least 1.5 mg per deciliter [133 μmol per liter]), hemolysis, thrombocytopenia, intrauterine growth restriction, or oligohydramnios. A blood pressure of 160/110 mm Hg or higher with proteinuria in the absence of any of the other features was also classified as severe preeclampsia. Patients were randomly assigned according to center (Epistat Services) in blocks of six, with the use of sealed opaque envelopes, to receive either nimodipine (60 mg orally every four hours) or magnesium sulfate according to the institutional protocol (a 6-g loading dose followed by an intravenous infusion of 2 g per hour, or a 4-g loading dose followed by an infusion of 1 g per hour). Treatment was continued for up to 24 hours ante partum (after which the protocol called for cesarean section unless delivery was imminent) and for 24 hours post partum. Measurement of blood levels of magnesium sulfate was not required. Blood pressure was measured with the use of automated monitors or manual sphygmomanometry (Korotkoff phase V). Urinary protein was measured with use of a semiquantitative method (dipstick) or, if available, a 24-hour urine collection.
The study was not blinded, because of logistic and economic constraints. The primary outcome measure (eclampsia) was binary, objective, and not subject to observer or measurement bias. Patients were treated according to the usual routine of each hospital, with no interference by the research group. Blood pressure was controlled with intravenous hydralazine for women whose systolic blood pressure was at least 160 mm Hg, whose diastolic blood pressure was at least 110 mm Hg, or whose overall blood pressure was at least 160/110 mm Hg for more than 20 minutes after the initiation of treatment.
The primary outcome measure was eclampsia (defined as a witnessed tonic–clonic convulsion) at any time from the initiation of study-drug administration until 24 hours post partum. Secondary outcome measures included blood-pressure control, complications and adverse drug effects, complications of labor and delivery, and indicators of fetal and neonatal condition. Postpartum hemorrhage (as recorded in the chart) was defined as estimated blood loss in the 24 hours after delivery of more than 500 ml in the case of vaginal delivery and of more than 1000 ml in the case of cesarean delivery.
Women in the nimodipine group who had a seizure received magnesium sulfate. Women who had a seizure while receiving magnesium sulfate continued to receive this drug according to the institutional regimen.
We initially planned to study 1000 patients per group, with interim analyses conducted every six months by an independent trial monitor and adjusted for multiple analyses with use of the Lan–DeMets method. The study was terminated early (August 2000) when a planned interim analysis showed a significantly higher rate of seizure in the nimodipine group.
All statistical analyses were performed with the use of SAS software (version 8, SAS Institute). The Wilk–Shapiro test was used to check the normality of distribution. The two groups were compared with use of analysis of variance, the two-sample t-test, Wilcoxon's rank–sum test, Fisher's exact test, the chi-square test, or logistic regression, as appropriate. Univariate analyses were conducted to identify demographic and clinical variables associated with the occurrence of seizures. Statistically significant variables were identified with the use of Fisher's exact test and univariate logistic regression. Variables that were significantly associated with seizure in the univariate analyses were included as covariates in a multiple logistic-regression analysis, along with other selected variables that were considered to warrant evaluation.
The type of anesthesia was classified as none or local infiltration only, regional (epidural or spinal), and general. The type of anesthesia was excluded from the overall analysis of seizures and was analyzed only in the group of patients who had a postpartum seizure (these patients were all in the nimodipine group). The antepartum effect of anesthesia could not be analyzed, because of uncertainty about the timing of the administration of anesthesia (before or after the seizure).
The odds ratios calculated from logistic regression were considered to provide a reasonable estimate of the risk ratio.17 In comparisons that contained a zero frequency cell, the logit estimator used for the risk ratio incorporated a correction of 0.5 in every cell and a confidence interval could not be obtained. All significance tests were two-tailed, with an α level of 0.05.
Bayer provided the nimodipine. This sponsor was not involved with the design of the study, the interpretation of the data, or the writing of this report. The investigators had full access to the data.
Results
We enrolled 1750 patients from July 1995 until November 2000. The Appendix shows the number of patients enrolled and the number who received study drug at each site. Data were available for 1650 of 1750 patients (94.3 percent): 819 of the 1650 were given nimodipine, and 831 were given magnesium sulfate. A total of 99 patients were enrolled, were assigned a study number, and underwent randomization but did not receive either drug. In most cases this was because they gave birth before the drug could be administered or because of logistic issues that prevented timely administration of the study drug. Hence, data sheets were not completed on these patients. One patient in the magnesium sulfate group was withdrawn from the study because the induction of labor was stopped and conservative management instituted. The median antepartum duration of treatment was 8.8 hours in the magnesium sulfate group and 8.1 hours in the nimodipine group.
Base-line demographic and clinical characteristics were generally similar in the two groups (Table 1Table 1
Base-Line Characteristics of the Study Population.); the only exception was that base-line systolic blood pressure was slightly higher in the magnesium sulfate group (P=0.04). No significant differences between groups were found in any of the recorded laboratory variables: hematocrit, platelet count, alanine aminotransferase level, aspartate aminotransferase level, uric acid level, creatinine level, blood urea nitrogen level, sodium level, or potassium level (data not shown).Patients given nimodipine were significantly more likely to have a seizure than those who received magnesium sulfate (2.6 percent vs. 0.8 percent, P=0.01) (Table 2Table 2
Maternal Complications.); the crude relative risk of seizure associated with nimodipine use, as compared with magnesium sulfate use, was 3.0 (95 percent confidence interval, 1.3 to 7.1). Twelve of the 21 patients in the nimodipine group who had a seizure did so in the antepartum period; 9 had a postpartum seizure. All seven of the women who had a seizure while receiving magnesium sulfate did so in the antepartum period. Although the nimodipine group had a higher rate of antepartum seizure than the magnesium sulfate group (1.5 percent vs. 0.8 percent), the difference was not significant (P=0.26). In the postpartum period, however, patients given nimodipine had a significantly higher rate of seizure than those who received magnesium sulfate (9 of 819 vs. 0 of 831; 1.1 percent vs. 0 percent; P=0.01). Three patients who initially received nimodipine had further seizures despite subsequent treatment with magnesium sulfate in the postpartum period.Women who received magnesium sulfate were more likely than women who received nimodipine to require hydralazine for blood-pressure control and to have flushing after drug administration (Table 2). There was also a higher incidence of postpartum hemorrhage in the magnesium sulfate group. There was a tendency toward more respiratory difficulty in the magnesium sulfate group, although this difference was not significant (P=0.06). Other maternal and neonatal outcomes did not differ significantly between groups (Table 2 and Table 3Table 3
Type of Delivery and Neonatal Complications.).After adjustment for the covariates listed in Table 4Table 4
Risk Factors for Seizure., the adjusted risk ratio associated with the use of nimodipine, as compared with that of magnesium sulfate was similar to the unadjusted risk ratio (3.1; 95 percent confidence interval, 1.3 to 7.3). Table 4 shows the statistically significant risk factors that were found to be associated with eclampsia.There were no significant differences between groups in the type of anesthesia they received (P=0.24). Only in the nimodipine group was the risk of postpartum seizure related to the type of anesthesia (P<0.01). None of the 250 women who received either no anesthesia or local anesthesia for delivery had a seizure, whereas seizure occurred in 3 of 392 patients who had regional anesthesia (0.8 percent) and in 6 of 86 who had general anesthesia (7.0 percent).
There was no significant difference between the two groups in the mean arterial pressure recorded before an antepartum seizure (mean [±SD], 124±17 mm Hg among 12 patients in the nimodipine group and 115±11 mm Hg among 7 patients in the magnesium sulfate group; P=0.22). In addition, the 19 women who had an antepartum seizure did not have a significantly higher mean arterial pressure at admission than those who did not have an antepartum seizure (131±20 mm Hg vs. 125±16 mm Hg, P=0.35). Base-line blood pressures and overall blood-pressure readings were similar in the two groups (data not shown), although the magnesium sulfate group more often required hydralazine. Among the patients whose initial mean arterial pressure exceeded 126 mm Hg, fewer in the nimodipine group than in the magnesium sulfate group required hydralazine for blood-pressure control (57.8 percent vs. 66.7 percent, P=0.04). Patients in the nimodipine group who required hydralazine were more likely to have eclampsia than patients in the magnesium sulfate group who required hydralazine (4.0 percent vs. 1.1 percent, P=0.01). Among patients who did not receive hydralazine, the rate of eclampsia was 1.4 percent in the nimodipine group and 0.5 percent in the magnesium sulfate group (P=0.30). Patients who required hydralazine had significantly higher blood-pressure values on admission than those who did not require hydralazine (data not shown). The increased risk of seizure associated with nimodipine persisted after adjustment for hydralazine use and systolic blood pressure at admission (Table 4).
The mean arterial pressure in the nimodipine group was reduced by a mean of 8.2 percent in the first hour after drug administration, and this reduction was maintained at three hours (8.3 percent). There was a 4.2 percent decrease in mean arterial pressure during the first hour in the magnesium sulfate group, and a 7.2 percent decrease within three hours.
Discussion
This study showed that parenterally administered magnesium sulfate is significantly better than oral nimodipine at preventing eclamptic seizures in women with severe preeclampsia. This difference was especially apparent in the postpartum period.
Although we compared magnesium sulfate with nimodipine, the recent MAGPIE trial12 compared magnesium sulfate with placebo in women with mild or severe preeclampsia and also demonstrated a beneficial effect of magnesium sulfate. In that study, there was also a lower maternal mortality rate in the magnesium sulfate group, although the difference was not significant. On the basis of these findings, there is now a considerable effort to promote the prophylactic use of magnesium sulfate in countries where its use was previously not the norm. Despite this, neither the cause of eclampsia nor the mechanism of action of magnesium sulfate as a seizure prophylactic is known.
It has been hypothesized that cerebral vasospasm and resultant ischemia are the predominant cause of eclampsia. If this were true then a specific cerebral vasodilator would be more effective at relieving vasospasm (and thus a better drug to prevent eclampsia) than magnesium sulfate. Our findings do not support this hypothesis.
A recent report18 on the cerebral hemodynamic changes in patients with preeclampsia may explain our findings, since it suggests that elevated cerebral perfusion pressure, rather than decreased cerebral blood flow, is the primary cause of injury. Increased cerebral perfusion pressure is believed to result in “cerebral barotrauma” and vasogenic (and, rarely, cytotoxic) edema. Nimodipine has been shown to increase cerebral perfusion pressure in patients with preeclampsia, whereas magnesium sulfate decreases it.19 Our finding that nimodipine is less effective than magnesium sulfate in preventing seizures suggests that seizures in patients with eclampsia that are not the result of obvious hemorrhage are more likely to be due to overperfusion (hypertensive encephalopathy)18,20-24 than ischemia. The higher rate of seizure in the nimodipine group may be explained on the basis of the nimodipine-induced reduction in protective vasoconstriction, which initiated or worsened overperfusion. This effect may be amplified in the postpartum period when the levels of constrictor substances released by the placenta25 are reduced. We observed a higher rate of seizure post partum, but not ante partum, in the nimodipine group than in the magnesium sulfate group.
The increased risk of seizure associated with elevated cerebral perfusion pressure may be compounded by the use of anesthetic agents or potent vasodilator drugs that interfere with cerebral autoregulation26 or by clinically significant volume expansion (such as through iatrogenic infusion of fluid or autologous uterine transfusion at the time of uterine contraction post partum). We found that women who required hydralazine for blood-pressure control were more likely to have a convulsion when they were given nimodipine than when they were given magnesium sulfate. Although the number of patients studied was small and the implications of this finding are not clear, in these patients the combination of a potent specific cerebral vasodilator (nimodipine) and a drug that prevents functional cerebral autoregulation (hydralazine)26 may have caused hypertensive encephalopathy.
Magnesium sulfate has been traditionally thought to have a transient hypotensive effect.27 In a third of women whose mean arterial pressure exceeded 126 mm Hg at admission, no drug other than magnesium sulfate was required for blood-pressure control. Although this difference may simply represent the effect of bed rest, a change in position, or the use of anesthesia, this observation warrants further study. The fact that no patient in this study died, had an intracranial hemorrhage, or had permanent renal or liver failure suggests that the degree of blood-pressure reduction associated with the administration of magnesium sulfate can be regarded as safe.
Although our analysis suggested that magnesium sulfate was associated with an increased risk of postpartum hemorrhage and respiratory difficulty, we do not believe that these are major risks of this therapy. These findings came to light as the result of post hoc analyses and were not anticipated a priori. The average estimated blood loss was similar in the two groups at the time of delivery, and we did not collect data on the need for blood transfusion. Respiratory difficulty was not objectively measured, and we relied on the subjective assessment of the delivery team. Neither of these two complications was reported as being associated with magnesium sulfate in the MAGPIE trial.12
We also found that chronic hypertension, a systolic blood pressure of more than 180 mm Hg at admission, the need for additional hydralazine, low blood sodium levels, and a young age were independent risk factors for eclampsia in women with severe preeclampsia. Although underlying hypertension, extremely elevated blood pressure, and young age have been previously reported as risk factors for eclampsia,28 the association of eclampsia with low sodium levels is less well known. The findings that regional and general anesthesia were associated with a higher risk of seizure than either no anesthesia or local anesthesia among patients taking nimodipine raise the possibility that these medications have an additive cerebral excitatory interrelation that magnesium sulfate does not. Given that these secondary findings were not the result of a priori hypotheses and may be the result of confounding factors, they should be regarded as hypothesis-generating observations.
Our study demonstrates that magnesium sulfate is more effective than nimodipine in preventing eclampsia in women with severe preeclampsia and reinforces the use of magnesium sulfate as the standard of care against which potential alternatives should be measured. Finally, the lack of effectiveness of nimodipine, a cerebral vasodilator, supports the hypothesis that eclampsia may be caused by cerebral overperfusion rather than decreased cerebral blood flow.
Supported by a grant from the Orphan Products Division of the Food and Drug Administration and by a grant from Bayer.
Source Information
From the Departments of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City (M.A.B.); Intermountain Health Care Utah Valley Regional Medical Center, Provo, Utah (M.A.B.); the University of Cape Town, Cape Town, South Africa (J.A.); the University of Texas Medical Branch, Galveston (G.R.S.); and the University of Texas School of Public Health, Houston (J.C.A.).
Address reprint requests to Dr. Belfort at 1034 N. 500 West, Provo, UT 84604, or at uvmbelfo@ihc.com.
The members of the study group are listed in the Appendix.
Appendix
The members of the Nimodipine Study Group were as follows (the numbers in parentheses are the numbers of patients who received at least one dose of study drug and the total numbers enrolled): John Anthony, University of Cape Town, Cape Town, South Africa (806/882); Maria Nobrega de Oliveira, Maternidade Escola J. Cicco, Natal, Brazil (282/303); Michael A. Belfort, Baylor College of Medicine, Houston (158/159); Omur Taskin, Inonu University School of Medicine, Malatya, Turkey (79/79); Jack Moodley, Nelson Mandela Medical School, Durban, South Africa (56/56); Jorge Carillo, Hospital Padre Hurtado, Santiago, Chile (51/52); Mario Festin, University of the Philippines, Manila (53/53); Liliana Voto, Fundacion Miguel Marguiles, Buenos Aires, Argentina (39/39); David Adair, Louisiana State University Medical Center, Shreveport (34/34); Baha Sibai, University of Tennessee, Memphis (33/34); Bjorn Uys, Frere Hospital, East London, South Africa (22/22); Jose Garrido Calderon, Esquina J.J. Perez, Santo Domingo, Dominican Republic (15/15); James W. Van Hook, University of Texas Medical Branch, Galveston (12/12); and Claudia Maria Vilas Freire, Maternidade Odete Valadares, Bello Horizonte, Brazil (10/10).
- References
References
1
Panchal S ,Arria AM ,Labhsetwar SA . Maternal mortality during hospital admission for delivery: a retrospective analysis using a state-maintained database. Anesth Analg 2001;93:134-141
CrossRef | Web of Science | Medline2
Sawhney H ,Aggarwal N ,Biswas R ,Vasishta K ,Gopalan S . Maternal mortality associated with eclampsia and severe preeclampsia of pregnancy. J Obstet Gynaecol Res 2000;26:351-356
CrossRef | Medline3
Will AD ,Lewis KL ,Hinshaw DB Jr , et al. Cerebral vasoconstriction in toxemia. Neurology 1987;37:1555-1557
Web of Science | Medline4
Trommer BL ,Homer D ,Mikhael MA . Cerebral vasospasm and eclampsia. Stroke 1988;19:326-329
CrossRef | Web of Science | Medline5
Horn EH ,Filshie M ,Kerslake RW ,Jaspan T ,Worthington BS ,Rubin PC . Widespread cerebral ischaemia treated with nimodipine in a patient with eclampsia. BMJ 1990;301:794-794
CrossRef | Web of Science | Medline6
Van den Veyver IB ,Belfort MA ,Rowe TF ,Moise KJ . Cerebral vasospasm in eclampsia: transcranial Doppler ultrasound findings. J Matern Fetal Med 1994;3:9-13
CrossRef7
Pritchard JA . The use of the magnesium ion in the management of eclamptogenic toxemias. Surg Gynecol Obstet 1955;100:131-140
Web of Science | Medline8
Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995;345:1455-1463[Erratum, Lancet 1995;346:258.]
Web of Science | Medline9
Sibai BM . Magnesium sulfate is the ideal anticonvulsant in preeclampsia-eclampsia. Am J Obstet Gynecol 1990;162:1141-1145
Web of Science | Medline10
Coetzee EJ ,Dommisse J ,Anthony J . A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. Br J Obstet Gynaecol 1998;105:300-303
CrossRef | Medline11
Lucas MJ ,Leveno KJ ,Cunningham FG . A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201-205
Full Text | Web of Science | Medline12
Do women with pre-eclampsia, and their babies, benefit from magnesium sulfate? The Magpie Trial: a randomised, placebo-controlled trial. Lancet 2002;359:1877-1890
CrossRef | Web of Science | Medline13
Belfort MA ,Moise KJ Jr . Effect of magnesium sulfate on maternal brain blood flow in preeclampsia: a randomized, placebo-controlled study. Am J Obstet Gynecol 1992;167:661-666
Web of Science | Medline14
van Gijn J ,Rinkel GJ . Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001;124:249-278
CrossRef | Web of Science | Medline15
Belfort MA ,Saade GR ,Moise KJ Jr , et al. Nimodipine in the management of preeclampsia: maternal and fetal effects. Am J Obstet Gynecol 1994;171:417-424
Web of Science | Medline16
ACOG technical bulletin no. 219. Washington, D.C.: American College of Obstetricians and Gynecologists, January 1996.
17
Fleiss JL. Statistical methods for rates and proportions. 2nd ed. New York: John Wiley, 1981:64-5.
18
Belfort MA ,Varner MW ,Dizon-Townson DS ,Grunewald C ,Nisell H . Cerebral perfusion pressure, and not cerebral blood flow, may be the critical determinant of intracranial injury in preeclampsia: a new hypothesis. Am J Obstet Gynecol 2002;187:626-634
CrossRef | Web of Science | Medline19
Belfort MA ,Saade GR ,Yared M , et al. Change in estimated cerebral perfusion pressure after treatment with nimodipine or magnesium sulfate in patients with preeclampsia. Am J Obstet Gynecol 1999;181:402-407
CrossRef | Web of Science | Medline20
Richards A ,Graham D ,Bullock R . Clinicopathological study of neurological complications due to hypertensive disorders of pregnancy. J Neurol Neurosurg Psychiatry 1988;51:416-421
CrossRef | Web of Science | Medline21
Donaldson JO . Eclamptic hypertensive encephalopathy. Semin Neurol 1988;8:230-233
CrossRef | Web of Science | Medline22
Schwartz RB ,Jones KM ,Kalina P , et al. Hypertensive encephalopathy: findings on CT, MR imaging, and SPECT imaging in 14 cases. AJR Am J Roentgenol 1992;159:379-383
Web of Science | Medline23
Zeeman GG ,Twickler DM ,Cunningham FG . Pathogenesis of cerebral lesions in eclampsia as determined by magnetic-resonance and diffusion-weighted imaging. Am J Obstet Gynecol 2001;185:Suppl:S168-S168 abstract.
Web of Science24
Morriss MC ,Twickler DM ,Hatab MR ,Clarke GD ,Peshock RM ,Cunningham FG . Cerebral blood flow and cranial magnetic resonance imaging in eclampsia and severe preeclampsia. Obstet Gynecol 1997;89:561-568
CrossRef | Web of Science | Medline25
Boura AL ,Walters WA . Autacoids and the control of vascular tone in the human umbilical-placental circulation. Placenta 1991;12:453-477
CrossRef | Web of Science | Medline26
Overgaard J ,Skinhoj E . A paradoxical cerebral hemodynamic effect of hydralazine. Stroke 1975;6:402-410
CrossRef | Web of Science | Medline27
Cotton DB ,Gonik B ,Dorman KF . Cardiovascular alterations in severe pregnancy-induced hypertension: acute effects of intravenous magnesium sulfate. Am J Obstet Gynecol 1984;148:162-165
Web of Science | Medline28
Mahmoudi N, Graves SW, Solomon CG, Repke JT, Seely EW. Eclampsia: a 13-year experience at a United States tertiary care center. J Women's Health Gend Based Med 1999;8:495-500.
- Citing Articles (65)
Citing Articles
1
Caren G. Solomon, Ellen W. Seely. (2011) Hypertension in Pregnancy. Endocrinology & Metabolism Clinics of North America 40:4, 847-863
CrossRef2
Mary A. Vadnais, Sarosh Rana, Hayley S. Quant, Saira Salahuddin, Laura E. Dodge, Kee-Hak Lim, S. Ananth Karumanchi, Michele R. Hacker. (2011) The impact of magnesium sulfate therapy on angiogenic factors in preeclampsia. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health
CrossRef3
Susanne Herroeder, Marianne E. Schönherr, Stefan G. De Hert, Markus W. Hollmann. (2011) Magnesium—Essentials for Anesthesiologists. Anesthesiology 114:4, 971-993
CrossRef4
Projestine S Muganyizi, Mohammed S Shagdara. (2011) Predictors of extra care among magnesium sulphate treated eclamptic patients at Muhimbili National Hospital, Tanzania. BMC Pregnancy and Childbirth 11:1, 41
CrossRef5
Sung Wook Kang, Seok-Keun Choi, Eunkuk Park, Su-Jin Chae, Samjin Choi, Hyo Jin Joo, Gi-Ja Lee, Hun-Kuk Park. (2011) Neuroprotective effects of magnesium-sulfate on ischemic injury mediated by modulating the release of glutamate and reduced of hyperreperfusion. Brain Research 1371, 121-128
CrossRef6
John W. Kevill, Eduardo Gonzalez-Toledo. 2011. Epilepsy and Pregnancy. , 91-121.
CrossRef7
Dimitris P. Papadopoulos, Iordanis Mourouzis, Costas Thomopoulos, Thomas Makris, Vasilios Papademetriou. (2010) Hypertension crisis. Blood Pressure 19:6, 328-336
CrossRef8
Lelia Duley, A Metin Gülmezoglu, David J Henderson-Smart, Doris Chou, Lelia Duley. 2010. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. .
CrossRef9
Santiago Ortega-Gutierrez, Stephan A. Mayer. (2010) Is the Magnesium Era for Aneurysmal Subarachnoid Hemorrhage Over?. Current Neurology and Neuroscience Reports 10:6, 420-422
CrossRef10
Gary A. Dildy, Michael A. Belfort. 2010. Complications of Pre-eclampsia. , 438-465.
CrossRef11
Lelia Duley, Hosam E Matar, Muhammad Qutayba Almerie, David R Hall, Lelia Duley. 2010. Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia. .
CrossRef12
Susan W. Lee, Steve S. Chung. (2010) A review of the effects of vitamins and other dietary supplements on seizure activity. Epilepsy & Behavior 18:3, 139-150
CrossRef13
Belinda Jim, Shuchita Sharma, Tewabe Kebede, Anjali Acharya. (2010) Hypertension in Pregnancy. Cardiology in Review 18:4, 178-189
CrossRef14
Li Ma, Wei-guo Liu, Jian-min Zhang, Gao Chen, Jing Fan, Han-song Sheng. (2010) Magnesium sulphate in the management of patients with aneurysmal subarachnoid haemorrhage: A meta-analysis of prospective controlled trials. Brain Injury 24:5, 730-735
CrossRef15
Liewei Wang. (2010) Pharmacogenomics: a systems approach. Wiley Interdisciplinary Reviews: Systems Biology and Medicine 2:1, 3-22
CrossRef16
Xu-Dong Zhao, Yi-Ting Zhou, Xin Zhang, Zong Zhuang, Ji-Xin Shi. (2009) A meta analysis of treating subarachnoid hemorrhage with magnesium sulfate. Journal of Clinical Neuroscience 16:11, 1394-1397
CrossRef17
Jeffrey J. Fletcher, Andreas H. Kramer, Thomas P. Bleck, Nina J. Solenski. (2009) Overlapping Features of Eclampsia and Postpartum Angiopathy. Neurocritical Care 11:2, 199-209
CrossRef18
M Klein, G Fesl, H-W Pfister, A Straube, H Brückmann, L-A Hoffmann, T Pfefferkorn. (2009) Intra-arterial nimodipine in progressive postpartum cerebral angiopathy. Cephalalgia 29:2, 279-282
CrossRef19
P. Diemunsch, B. Langer, E. Noll. 2009. Principes généraux de la prise en charge hospitalière de la prééclampsie. , 95-111.
CrossRef20
G. Beucher, T. Simonet, M. Dreyfus. 2009. Devenir à court terme des patientes ayant développé une prééclampsie sévère. , 259-269.
CrossRef21
Gerda G. Zeeman, Marilyn J. Cipolla, F. Gary Cunningham. 2009. Cerebrovascular (Patho)Physiology in Preeclampsia/Eclampsia. , 227-247.
CrossRef22
Jason G. Umans, Edgardo J. Abalos, Marshall D. Lindheimer. 2009. Antihypertensive Treatment. , 369-387.
CrossRef23
Kenneth J. Leveno, F. Gary Cunningham. 2009. Management. , 389-414.
CrossRef24
Kentaro Mori, Masahiro Miyazaki, Junko Iwata, Takuji Yamamoto, Yasuaki Nakao. (2008) Intracisternal infusion of magnesium sulfate solution improved reduced cerebral blood flow induced by experimental subarachnoid hemorrhage in the rat. Neurosurgical Review 31:2, 197-203
CrossRef25
Sanne M. Dorhout Mees, . (2008) Magnesium in aneurysmal subarachnoid hemorrhage (MASH II) phase III clinical trial MASH-II study group. International Journal of Stroke 3:1, 63-65
CrossRef26
Alison G. Cahill, George A. Macones, Anthony O. Odibo, David M. Stamilio. (2007) Magnesium for Seizure Prophylaxis in Patients With Mild Preeclampsia. Obstetrics & Gynecology 110:3, 601-607
CrossRef27
Robert A Dyer, Jenna L Piercy, Anthony R Reed. (2007) The role of the anaesthetist in the management of the pre-eclamptic patient. Current Opinion in Anaesthesiology 20:3, 168-174
CrossRef28
Bibi Shahnaz Aali, Payam Khazaeli, Fatemeh Ghasemi. (2007) Ionized and total magnesium concentration in patients with severe preeclampsia-eclampsia undergoing magnesium sulfate therapy. Journal of Obstetrics and Gynaecology Research 33:2, 138-143
CrossRef29
Jeffrey J. Pasternak, William L. Lanier. (2007) Neuroanesthesiology Review-2006. Journal of Neurosurgical Anesthesiology 19:2, 70-92
CrossRef30
Andrew R. Haas, Paul E. Marik. (2006) CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Current Diagnosis and Management of Hypertensive Emergency. Seminars in Dialysis 19:6, 502-512
CrossRef31
Martina Stippler, Elizabeth Crago, Elad I. Levy, Mary E. Kerr, Howard Yonas, Michael B. Horowitz, Amin Kassam. (2006) Magnesium infusion for vasospasm prophylaxis after subarachnoid hemorrhage. Journal of Neurosurgery 105:5, 723-729
CrossRef32
F.J. González Sendra, J. Jurado Palomo, M. Mora Rillo, R.M. Regojo Zapata, J.I. Bernardino de la Serna, J. García Puig. (2006) Crisis convulsiva generalizada de origen metabólico. Revista Clínica Española 206:9, 451-452
CrossRef33
Michael A. Belfort, Steven L. Clark, Baha Sibai. (2006) Cerebral Hemodynamics in Preeclampsia: Cerebral Perfusion and the Rationale for an Alternative to Magnesium Sulfate. Obstetrical & Gynecological Survey 61:10, 655-665
CrossRef34
Richard M. Weinshilboum, Liewei Wang. (2006) Pharmacogenetics and Pharmacogenomics: Development, Science, and Translation. Annual Review of Genomics and Human Genetics 7:1, 223-245
CrossRef35
Lelia Duley, David J Henderson-Smart, Shireen Meher, Lelia Duley. 2006. Drugs for treatment of very high blood pressure during pregnancy. .
CrossRef36
Jennifer Hirshfeld-Cytron, Chun Lam, S Ananth Karumanchi, Marshall Lindheimer. (2006) Late Postpartum Eclampsia: Examples and Review. Obstetrical & Gynecological Survey 61:7, 471-480
CrossRef37
Samuel Liévano, Lourdes Alarcón, Bibiana Chávez–Munguía, Lorenza González–Mariscal. (2006) Endothelia of term human placentae display diminished expression of tight junction proteins during preeclampsia. Cell and Tissue Research 324:3, 433-448
CrossRef38
George K. C. Wong, Matthew T. V. Chan, Wai S. Poon, Ronald Boet, Tony Gin. (2006) Magnesium therapy within 48 hours of an aneurysmal subarachnoid hemorrhage: neuro-panacea. Neurological Research 28:4, 431-435
CrossRef39
Robert Schmid-Elsaesser, Matthias Kunz, Stefan Zausinger, Stefan Prueckner, Josef Briegel, Hans-Jakob Steiger. (2006) Intravenous Magnesium versus Nimodipine in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized Study. Neurosurgery 58:6, 1054-1065
CrossRef40
George K. C. Wong, Matthew T. V. Chan, Ronald Boet, Wai S. Poon, Tony Gin. (2006) Intravenous Magnesium Sulfate After Aneurysmal Subarachnoid Hemorrhage: A Prospective Randomized Pilot Study. Journal of Neurosurgical Anesthesiology 18:2, 142-148
CrossRef41
R Mittendorf, O Dammann, K-S Lee. (2006) Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor. Journal of Perinatology 26:1, 57-63
CrossRef42
Michael A. Proschan, Eric Leifer, Qing Liu. (2005) Adaptive Regression. Journal of Biopharmaceutical Statistics 15:4, 593-603
CrossRef43
M. Todd Fontenot, David F. Lewis, J. Brian Frederick, Yuping Wang, Emily A. DeFranco, Lynn J. Groome, Arthur T. Evans. (2005) A prospective randomized trial of magnesium sulfate in severe preeclampsia: Use of diuresis as a clinical parameter to determine the duration of postpartum therapy. American Journal of Obstetrics and Gynecology 192:6, 1788-1793
CrossRef44
Baha M Sibai. (2005) Magnesium Sulfate Prophylaxis in Preeclampsia: Evidence From Randomized Trials. Clinical Obstetrics and Gynecology 48:2, 478-488
CrossRef45
S. R. Wilson, N. P. Hirsch, I. Appleby. (2005) Management of subarachnoid haemorrhage in a non-neurosurgical centre. Anaesthesia 60:5, 470-485
CrossRef46
L TSEN. (2005) What?s new and novel in obstetric anesthesia? Contributions from the 2003 scientific literature. International Journal of Obstetric Anesthesia 14:2, 126-146
CrossRef47
J Andrew McKee, Randall P. Brewer, Gary E. Macy, Barbara Phillips-Bute, Kurt A. Campbell, Cecil O. Borel, James D. Reynolds, David S. Warner. (2005) Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia*. Critical Care Medicine 33:3, 661-666
CrossRef48
Kjersti M Aagaard-Tillery, Michael A Belfort. (2005) Eclampsia: Morbidity, Mortality, and Management. Clinical Obstetrics and Gynecology 48:1, 12-23
CrossRef49
Lelia Duley. (2005) Evidence and practice: the magnesium sulphate story. Best Practice & Research Clinical Obstetrics & Gynaecology 19:1, 57-74
CrossRef50
Marian H. Ascarelli, Venessia Johnson, Holly McCreary, Julie Cushman, Warren L. May, James N. Martin. (2005) Postpartum Preeclampsia Management With Furosemide: A Randomized Clinical Trial. Obstetrics & Gynecology 105:1, 29-33
CrossRef51
Peter W. Kaplan. (2004) Neurologic aspects of eclampsia. Neurologic Clinics 22:4, 841-861
CrossRef52
Peter G Pryde, Susan Janeczek, Robert Mittendorf. (2004) Risk–benefit effects of tocolytic therapy. Expert Opinion on Drug Safety 3:6, 639-654
CrossRef53
Nikolaus A. Haas, Jan Kemke, Ingram Schulze-Neick, Peter E. Lange. (2004) Effect of increasing doses of magnesium in experimental pulmonary hypertension after acute pulmonary embolism. Intensive Care Medicine 30:11, 2102-2109
CrossRef54
Baha M Sibai. (2004) Magnesium sulfate prophylaxis in preeclampsia: lessons learned from recent trials. American Journal of Obstetrics and Gynecology 190:6, 1520-1526
CrossRef55
Ruth Landau, Jason A. Scott, Richard M. Smiley. (2004) Magnesium-induced vasodilation in the dorsal hand vein. BJOG: An International Journal of Obstetrics and Gynaecology 111:5, 446-451
CrossRef56
R. Mittendorf, P.G. Pryde, N. Roizen. (2004) Second overview of relationships between antenatalpharmacologic magnesium sulfate and neurologic outcomes in children. Journal of Perinatal Medicine 32:3, 201-210
CrossRef57
Jeanette A.M Maier, Daniela Bernardini, Yves Rayssiguier, Andrzej Mazur. (2004) High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1689:1, 6-12
CrossRef58
Joanne Douglas, Alison Macarthur. (2003) Best evidence in anesthetic practice Prevention: Magnesium sulfate reduces the risk of eclampsia in women with pre-eclampsia. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 50:10, 1035-1038
CrossRef59
Antonio E Frias, Michael A Belfort. (2003) Post Magpie: how should we be managing severe preeclampsia?. Current Opinion in Obstetrics and Gynecology 15:6, 489-495
CrossRef60
Michael A. Sloan, Barney J. Stern. (2003) Cerebrovascular disease in pregnancy. Current Treatment Options in Neurology 5:5, 391-407
CrossRef61
(2003) Prevention of Eclampsia. New England Journal of Medicine 348:21, 2154-2155
Full Text62
Lelia Duley, A Metin Gülmezoglu, David J Henderson-Smart, Lelia Duley. 2003. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. .
CrossRef63
K.T. Shiverick, W. Slikker, S.J. Rogerson, R.K. Miller. (2003) Drugs and the Placenta—A Workshop Report. Placenta 24, S55-S59
CrossRef64
(2003) Hot Papers in the Literature. Journal of Women's Health 12:2, 193-198
CrossRef65
Greene, Michael F., . (2003) Magnesium Sulfate for Preeclampsia. New England Journal of Medicine 348:4, 275-276
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