Best Practice & Research Clinical Obstetrics and Gynaecology

Vol. 19, No. 1, pp. 5774, 2005

doi:10.1016/j.bpobgyn.2004.10.010
available online at http://www.sciencedirect.com

6
Evidence and practice: the magnesium
sulphate story
Lelia Duley*

MD (Hons), MSc (Epid), FRCOG

Obstetric Epidemiologist
Resource Centre for Randomised Trials, Institute of Health Sciences, Old Road, Oxford OX3 7LF, UK

There is now strong evidence from systematic reviews of randomised trials to support the use of
magnesium sulphate for the prevention and treatment of eclampsia. Magnesium sulphate more than
halves the risk of eclampsia for women with pre-eclampsia (relative risk (RR) 0.41, 95% confidence
interval (CI) 0.290.58; number needed to treat (NNT) 102 (95% CI 72173) compared to
placebo. For treatment of eclampsia, magnesium sulphate lowers the risk of maternal death
(RR 0.59, 95% CI 0.370.94) and of recurrence of further fits (RR 0.44, 95% CI 0.340.57)
compared to diazepam. Magnesium sulphate also reduces the risk of further fits compared
to phenytoin (RR 0.31, 95% CI 0.200.47) and to lytic cocktail (RR 0.09, 95% CI 0.030.24).
Key words: magnesium sulphate; eclampsia; pre-eclampsia; systematic reviews.

Eclampsia is defined as the occurrence of one or more convulsions superimposed on

the syndrome of pre-eclampsia. Pre-eclampsia is relatively common, complicating 28%
of pregnancies.1 Although a major cause of maternal morbidity, perinatal death, and
premature delivery, it is only rarely associated with maternal death. Eclampsia occurs
far less frequently, complicating between 1 in 100 and 1 in 1700 pregnancies in the
developing world13, and about 1 in 2000 pregnancies in Europe and other developed
countries.4 Compared to pre-eclampsia it carries a much higher risk of death for the
woman and her baby, however. In the UK, for example, 1 in 50 of the women who have
eclampsia will die.4
Over half a million women die each year of pregnancy-related causes, 99% of these
deaths occur in the developing world.5,6 Put another way, women in industrialised
countries have an average lifetime risk (calculated as the average number of pregnancies
multiplied by the risk associated with each pregnancy) of dying from pregnancy-related
causes of between 1 in 4000 and 1 in 10 000, whereas women in low- to middle-income
countries have a risk that is between 1 in 15 and 1 in 50. In poor countries, maternal
* Tel.: C44 1865 226 642; Fax: C44 1865 227173.
E-mail address: lelia.duley@ndm.ox.ac.uk
1521-6934/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved.

58 L. Duley

mortality is 100200 times higher than in Europe and North America.7 There is no
other public health statistic for which the disparity between developed and developing
countries is so wide. Although rare, eclampsia probably accounts for 50 000 maternal
deaths a year worldwide. In areas where maternal mortality is high, infection and
haemorrhage are the main causes of death but, as deaths from these causes become
less common, those associated with eclampsia and pre-eclampsia assume greater
importance. In the UK, eclampsia is a factor in 15% of direct maternal deaths.8
This chapter tells the story of magnesium sulphate for the prevention and treatment
of eclampsia. The story begins at the turn of the 19th century. It includes the evolution
of our understanding of the underlying disease, salutary lessons about the delays in
proper evaluation of care9, and concludes with a summary of the evidence from
systematic reviews. The incomplete postscript is about how to get this evidence into
practice.

EVOLUTION OF CARE FOR PREVENTION AND TREATMENT

OF ECLAMPSIA
The occurrence of seizures during pregnancy has been noted since ancient Egyptian
times, but was thought to be a form of epilepsy.10 In 1843, eclampsia was shown to be
associated with proteinuria and was assumed to be a disease of the kidneys during
pregnancy, a form of pregnancy nephritis.11 Measurement of blood pressure did not
begin until around 1910, so hypertension was not part of the diagnosis until much later.
Before the mid-19th century, management of eclampsia consisted largely of bleeding
and purging. Sedatives such as morphine and chloral hydrate were introduced but did
little to reduce the very high mortalitybetween 20 and 30%associated with
eclampsia.11,12 It was recognised that convulsions often ceased after delivery, and
interventions to expedite delivery became popular.
In the early 20th century, two contrasting approaches to the care of women with
eclampsia emerged. One was based on the belief that prompt termination of the
pregnancy would prevent disease progression and obstetric intervention should
therefore be maximal and early, the other aimed to prevent further fits and avoid
operative delivery.13,14 The rationale behind early policies for expectant management
was that heavy sedation would stabilise the woman and prevent further convulsions.
Later, agents believed to have a more specific anticonvulsant action were introduced.
One of the first drugs suggested to have a specific anticonvulsant effect for eclampsia
was magnesium sulphate (Horn 1906, from Ref. 12). Reports of the successful control
of convulsions due to tetanus gave impetus to its introduction for eclampsia.14,15 By the
1920s, magnesium sulphate was being used for eclampsia in Europe12 and in the United
States.1517 Although not everyone reported favourable results18, magnesium sulphate
administration became established clinical practice in several parts of the world. It
became the drug of choice in North America19 although, until recently, supported only
by data from uncontrolled case series.20,21 Despite the lack of adequate controls, these
reports had a huge influence on the clinical practice of several generations of
obstetricians.22 This use of magnesium sulphate was rapidly extended to women with
pre-eclampsia17,23, in the hope it would prevent the onset of eclampsia and so improve
outcome.24,25
For decades there has been huge geographical variation in the use of magnesium
sulphate. Places that looked to the United States for guidance used magnesium sulphate

Evidence and practice: magnesium sulphate 59

for both eclampsia and pre-eclampsia. In other countries, it was used hardly at all, more
conventional anticonvulsants such as diazepam or phenytoin being preferred. Part of
the scepticism about magnesium sulphate was the lack of any plausible hypothesis for
how it might work. The mode of action for magnesium sulphate is still not clearly
understood, but it might cause vasodilatation with subsequent reduction of cerebral
ischaemia26, and/or block some of the neuronal damage associated with ischaemia.27,28
A possible mechanism for vasodilatation is relaxation of smooth muscle. It has been
suggested that magnesium might have a generalised effect on all smooth muscle,
including the peripheral vasculature and uterus, hence the hypotheses that it might also
have antihypertensive and tocolytic effects. Alternatively, any effects of magnesium
sulphate in control of eclamptic convulsions might be, wholly or partially, through its
role as a blocker of N-methyl-D-aspartate (NMDA) receptors in the brain.27 These
NMDA receptors are activated in response to asphyxia, leading to calcium influx into
the neurons, which causes cell injury. Magnesium might block these receptors, so
reducing calcium influx and protecting the neurones.27,28
Case control studies have suggested that in utero exposure to magnesium
sulphate might reduce the risk of cerebral palsy for low birthweight (!1500 g)
babies.29 Later, there was concern that magnesium sulphate exposure for these
vulnerable babies might be associated with an increased mortality.30 It has been
argued that a link between exposure to magnesium sulphate before preterm birth
and an increase in mortality is unlikely31, and there are now data from a
randomised trial suggesting that such exposure is associated with a moderate
improvement in paediatric outcome.32
Two large collaborative trials have evaluated policies for the use of anticonvulsants
for the prevention and treatment of eclampsia.33,34 Magnesium sulphate is now the drug
of choice for both the prevention and treatment of eclampsia.35

PREVENTING THE ONSET OF ECLAMPSIA

The first question about magnesium sulphate as a prophylactic anticonvulsant for
women with pre-eclampsia is whether it reduces the risk of eclampsia. Even if it
does, additional information is required before magnesium sulphate can safely be
recommended for clinical practice; in particular, information is needed about the
size of any risk reduction, effects on other important outcomes for the woman and
child, and the disease severity at which benefits outweigh the risks. The methods
for the systematic review summarised below are described in detail elsewhere.36 In
brief, the review included randomised trials (Table 1) of any anticonvulsant for
women with pre-eclampsia, regardless of whether before or after delivery, whether
a singleton or multiple pregnancy, or whether an anticonvulsant had been given
before trial entry.
Magnesium sulphate versus placebo or no anticonvulsant
Six trials (11 444 women) compared magnesium sulphate with placebo or no
anticonvulsant. Magnesium sulphate is associated with more than a halving in the risk
of eclampsia (relative risk (RR) 0.41, 95% confidence intervals (CI) 0.290.58; risk
difference (RD) K0.01, 95% CI K0.02 to K0.01, number needed to treat (NNT) 102
(95% CI 72173) compared with placebo or no anticonvulsant. This relative risk is

Trial

Methods

Anticonvulsant versus none

Central telephone service (2037 women), or
consecutively numbered, sealed treatment
Magpie Trial
packs, stratified by centre (8104). Computer2002 (nZ
generated sequence. Five women excluded: 4
10 141)33
no data, 1 entered into wrong trial. 175
centres in 33 countries. 85% women from lowto middle-income countries
Sealed opaque envelopes containing cards
South Africa
labelled A or B. Cards consecutively num1998 (nZ
bered. Batches of 20, with equal A and B.
822)45
Identity of A and B changed periodically. 137
women (17%) excluded after randomisation
South Africa
Consecutively numbered sealed opaque
1994 (nZ
envelopes
46
228)
Taiwan 1995
(nZ64)47
USA-Memphis
1997 (nZ
135)48

Participants

Interventions

Uncertainty about whether to use MgSO4,

before birth or 24-hour postpartumCDBP
R90 mmHg, SBP R140 mmHg !2 30
60 minutes apart, R1Cproteinuria. Excluded:
hypersensitivity to Mg, hepatic coma with risk
of renal failure, myasthenia gravis

MgSO4: 4 g i.v. bolus. Then either 1 g/hour

infusion or 10 g i.m. followed by 5 g every
4 hours. Continued for 24 hours. Two centres
used 5 g i.m. then 2.5 g every 4 hours. Placebo:
by identical regimen. Dose halved if oliguria

Severe PE: R2 of DBP 110 mmHg, proteinuria,

symptoms of imminent eclampsia. Also, O16
years and no prior anticonvulsant

MgSO4: 4 g i.v. in 200 ml over 20 minutes, then

1 g/hour until 24 hours after delivery. Control:
placebo by same regimen. Both groups had
clonazepam at trial entry

DBP: 110 mmHg for 46 hoursCprotein and

delivery planned. Excluded if prior anticonvulsant (except phenobarbitone)

MgSO4: 4 g i.v. over 20 minutes, 10 g i.m., then

5 g i.m. every 4 hours for 24 hours. Control:
no anticonvulsant
MgSO4: 4 g i.v. over 10 minutes, then 1 g/hour
until 24 hours after delivery. Control: no
anticonvulsant

Randomised, no other information

BP 150/100 mmHg and R1 of 11 features of

PE. Excluded if IUD, or chronic HT

Sealed, sequentially numbered opaque envelopes

R37 weeks gestation with recent onset PE (BP

140/90 mmHg and proteinurea 300 mg in
24 hours). Excluded if severe PE, fetal malpresentation, congenital anomaly, non-reassuring fetal testing

MgSO4: 6 g i.v. bolus over 1520 minutes, then

infusion of 2 g/hour. Continued until 12 hours
postpartum. Placebo: saline solution by identical regimen

222 women with mild PE during labour.

Excluded: chronic HT, severe PE

MgSO4: 6 g i.v., then infusion of 2 g/hour.

Placebo: matching regimen

USA-TennesRandomised placebo-controlled trial. No

see 2003 (nZ
further information
49
222)
Magnesium sulphate versus phenytoin

60 L. Duley

Table 1. Characteristics of trials evaluating anticonvulsants for women with pre-eclampsia.

USA-Texas
1995 (nZ
2138)50

Numbered opaque envelopes

BP 140/90 mmHg. Excluded if postpartum,

delivery imminent or epilepsy

USA-Alabama
1995 (nZ54)51

Blinded computer-generated random number

tables

Singleton pregnancy, medical induction for PIH,

unfavourable cervix

USA-Maryland
1993a (nZ
115)52

Sealed opaque envelopes. 12 exclusions after

trial entry

BP 140/90 mmHg, or rise SBP 30 mmHg or

DBP 15 mmHg. Excluded if prior MgSO4 or
seizure disorder

MgSO4: 10 g i.m., then 5 g every 4 hours. If

severe PE, 4 g before first i.m. dose. Phenytoin:
1000 mg i.v. over 1 hour. 10 hours later,
500 mg orally
MgSO4: 4 g i.v., then infusion 2 g/hour. Phenytoin: 15 mg/kg over 2 hours then 200 mg i.v.
every 8 hours
MgSO4: 6 g i.v., then infusion 2 g/hour for
24 hours. Phenytoin: 10001500 mg, depending on weight. Serum levels to determine next
dose, for 24 hours

Magnesium sulphate versus diazepam

Mexico 1992
(nZ38)53

Numbered opaque envelopes

Denmark 2000
(nZ33)56

Numbered sealed opaque envelopes. Two

exclusions from MgSO4 group (1 withdrawal, 1
given methyl dopa)

DBP R110 mmHg plus proteinuria

MgSO4: 4 g i.v. over 15 minutes, then 1 g/hour

infusion. Diazepam: 30 mg in 500 ml 5%
glucose at 60 mg/hour
MgSO4: Pritchards regimen. Diazepam: not
stated

Antepartum women with severe PE and no

previous therapy. BP R140/90, R1Cproteinurea, R1 sign or symptom of imminent
eclampsia

MgSO4: either 6 g i.v. and 2 g/hour or 4 g i.v.

and 1 g/hour. Nimodipine: 60 mg 4 hourly,
orally. Continued for up to 24 hours postpartum

Nulliparous, singleton pregnancy and BP O

140/90 mmHg !2 over 3 hours. Excluded:
pre-existing HT, cardiac or renal disease, BP O
180/120 mmHg after hydralazine

MgCl2: 80 mmol i.v. in 24 hours, 40 mmol in

next 24 hours. Then 15 mmol/day MgOH2
orally until 3 days after delivery. Methyl dopa:
250 mg !4/day. After delivery reduced by
250 mg/day

BP, blood pressure; DBP, diastolic blood pressure; HT, hypertension; i.m., intramuscular; IUD, intrauterine death; i.v., intravenous; MgOH2, magnesium hydroxide;
MgSO4, magnesium sulphate; PE, pre-eclampsia; PIH, pregnancy-induced hypertension; PPH, postpartum haemorrhage; SBP, systolic blood pressure.
a
Women with eclampsia in these trials not included in this review.

Evidence and practice: magnesium sulphate 61

Malaysia 1994a
Consecutive sealed envelopes
(nZ28)54
Magnesium sulphate versus nimodipine
Nimodipine
Study Group
Sealed opaque envelopes. Blocks of 6
2003 (nZ
55
1750)
Magnesium sulphate versus methyl dopa

28 weeks, SBP R150 mmHg, DBP

R110 mmHg, proteinuria, at least one symptom. No epilepsy

Magnesium
n/N

01 severe pre-eclampsia
1/345
South Africa 1998
15/1297
South Trial 2002
15/112
South Africa 1994
1754
Subtotal (95% Cl)
Total events: 17 (Magnesium), 48 (Control)
2
Test for heterogeneity: Chi =3.73, df=2(P=0.15),I2=46.4%
Test for overall effect: Z=3.58 (P=0.0003)
02 not severe pre-eclampsia
USA - Tennessee 2003
0/109
Taiwan 1995
0/34
Magpie Trial 2002
25/3758
USA - Memphis 1997
1/67
3968
Subtotal (95% Cl)
Total events: 26 (Magnesium), 59 (Control)
Test for heterogeneity: Chi2=1.46, df=1(P=0.23),I2=31.7%
Test for overall effect: Z=3.53 (P=0.0004)
5722
Total (95% Cl)
Total events: 43 (Magnesium), 107 (Control)
Test for heterogeneity: Chi2=5.22, df=4(P=0.27),I2=23.4%
Test for overall effect: Z=5.02 (P<0.00001)

Control
n/N

RR (fixed)
95% cl

RR (fixed)
95% cl

11/340
37/1345
0/116
1801

0.09 [0.01, 0.69]

0.42 [0.23, 0.76]
3.11 [0.13, 75.76]
0.37 [0.22, 0.64]

0/113
0/30
59/3710
0/68
3921

Not estimable
Not estimable
0.42 [0.26, 0.67]
3.04 [0.13, 73.42]
0.44 [0.28, 0.69]

5722

0.41 [0.29, 0.58]

0.1

0.2

0.5

Favours magnesium

10

Favours control

Figure 1. Magnesium sulphate versus placebo or no anticonvulsant: effect on eclampsia (subgrouped by severity of pre-eclampsia).

62 L. Duley

Study
or sub-category

Evidence and practice: magnesium sulphate 63

consistent regardless of severity of pre-eclampsia (Figure 1) or of whether the women

were antepartum at trial entry, or of gestation at trial entry (data not shown).
Two trials (10 795 women) reported maternal deaths. Risk of dying was reduced by
46% for women allocated magnesium sulphate rather than placebo or no anticonvulsant, although this did not achieve statistical significance (RR 0.54, 95% CI 0.26
1.10). For the two trials (10 332 women) reporting serious maternal morbidity, the
relative risk was 1.08 (95% CI 0.891.32). For the individual measures of serious
morbidity, such as pneumonia, renal failure and liver failure, there was also no clear
evidence of an overall difference in effect between the two groups. There was a small
(3%) reduction in the need for antihypertensive therapy associated with the use of
magnesium sulphate rather than placebo or no anticonvulsant (RR 0.97, 95% CI 0.95
0.99).
For women randomised before delivery, the relative risk of placental abruption
was reduced if they were allocated magnesium sulphate rather than placebo (RR
0.64, 95% CI 0.500.83; RD K0.01, 95% CI K0.02 to 0.00; NNT 100, 95% CI 50
1000). Women allocated magnesium sulphate had a small (5%) increase in the risk
of caesarean section compared to those allocated placebo or no anticonvulsant (RR
1.05, 95% CI 1.011.10; RD 0.03, 95% CI 0.010.04; NNT 34, 95% CI 10025).
There was no evidence of a clinically important effect on the risk of induction of
labour (RR 0.99, 95% CI 0.941.04), postpartum haemorrhage (RR 0.96, 95% CI
0.881.05) or manual removal of placenta (RR 0.90, 95% CI 0.721.12).
For the babies, there was no overall difference in the risk of stillbirth or neonatal
death (three trials, 9961 women), although a small increase or decrease in mortality
associated with the use of magnesium sulphate remains possible (RR 1.04, 95% CI 0.93
1.15) (Figure 2). The result is consistent regardless of gestation at trial entry (data not
shown). For the composite outcome of death or in special care baby unit for O7 days,
there is also no clear evidence of a clinically important difference (RR 1.01, 95% CI
0.951.08). There was no clear evidence of any difference in neonatal morbidity
between the two groups.
Toxicity was uncommon, occurring in around 1% of women given magnesium
sulphate and 0.5% of those allocated placebo. There was no clear evidence of an
overall difference in the risk of absent or reduced tendon reflexes (RR 1.00, 95%
CI 0.701.42). Although respiratory depression and other respiratory problems
were rare (52/5344 versus 26/5333), the relative risk of these was increased for
women allocated magnesium sulphate (RR 1.98, 95% CI 1.243.15; NNT 206, 95%
CI 1000100). A quarter of women allocated magnesium sulphate had side effects
(24 versus 5%; RR 5.26, 95% CI 4.596.03; NNT 6, 95% CI 65). By far the most
common side effect was flushing. Problems at the injection site were more
common for women allocated magnesium sulphate than those allocated placebo,
and for those who had intramuscular (i.m.) as opposed to intravenous (i.v.)
treatment (i.m. 12 versus 8%; i.v. 5 versus 2%).
Magnesium sulphate versus phenytoin
Two trials (2241 women) compared magnesium sulphate with phenytoin.
Magnesium sulphate appears to be better than phenytoin at reducing the risk of
eclampsia (RR 0.05, 95% CI 0.000.84; RD 0.01, 95% CI K0.02 to 0.00; NNT 111,
95% CI 67333), although the number of events was small (0 versus 10).
Magnesium sulphate was associated with a greater risk of caesarean section than

64 L. Duley

Study
or sub-category

Magnesium
n/N

01 severe pre-eclampsia
South Africa 1994
20/117
234/1185
Magpie Trial 2002
38/348
South Africa 1998
Subtotal (95% Cl)
1650
Total events: 292 (Magnesium), 293 (Control)
Test for heterogeneity: Chi2=2.42, df=2(P=0.30),I2=17.5%
Test for overall effect: Z=0.30 (P=0.77)
02 not severe pre-eclampsia
Magpie Trial 2002
342/3353
3353
Subtotal (95% Cl)
Total events: 342 (Magnesium), 318 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z=0.63 (P=0.53)
5003
Total (95% Cl)
Total events: 634 (Magnesium), 611 (Control)
Test for heterogeneity: Chi2=2.50, df=3(P=0.48),I2=0%
Test for overall effect: Z=.067 (P=0.50)

Control
n/N

RR (fixed)
95% cl

RR (fixed)
95% cl
0.81 [0.48, 1.37]
1.00 [0.85, 1.18]
1.38 [0.87, 2.20]
1.02 [0.88, 1.18]

25/118
230/1219
28/354
1691

318/3267
3367

1.05 [0.91, 1.21]

1.05 [0.91, 1.21]

4958

1.04 [0.93, 1.15]

0.1

0.2

0.5

Favours magnesium

10

Favours control

Figure 2. Magnesium sulphate versus placebo or no anticonvulsant: effect on stillbirths and neonatal deaths (subgrouped by severity of pre-eclampsia).

Evidence and practice: magnesium sulphate 65

phenytoin (RR 1.21, 95% CI 1.051.41; RD 0.05, 95% CI 0.010.08; NNT 21 95%
CI 8312). There is no information on other important measures of maternal
morbidity. Confidence intervals for estimates of the differential effects on measures
of morbidity and mortality for the baby are wide, and cross the no effect line.
Magnesium sulphate versus nimodipine
One trial compared magnesium sulphate with nimodipine (1750 women). Fewer
women allocated magnesium sulphate, rather than nimodipine, had eclampsia (RR 0.33,
95% CI 0.140.77). Mortality for the baby is not reported.
Comparisons of other agents
Two trials (66 women) have compared magnesium sulphate with diazepam and another
has compared magnesium chloride with methyl dopa (31 women).
Discussion
There is strong evidence from placebo-controlled trials that, for women with preeclampsia, magnesium sulphate more than halves the relative risk of eclampsia. It
seems likely that it also leads to a clinically important reduction in the risk of
maternal death. The only other effects associated with magnesium sulphate are a
reduction in the risk of placental abruption and a small (5%) increase in the risk of
caesarean section. Side effects from magnesium sulphate are common, but
unpleasant rather than serious. There is no substantive effect on stillbirth or
neonatal mortality. Longer-term follow-up of the children is required to provide
reassurance that this apparent short-term safety continues into childhood, and to
test the hypothesis that exposure to magnesium sulphate might reduce the risk of
cerebral palsy for low birthweight infants. Such data from the Magpie Trial37 should
be available by the end of 2004.
The relative effect on eclampsia is consistent regardless of the severity of preeclampsia. Eclampsia is more common in women with severe pre-eclampsia than in
those with moderate or mild pre-eclampsia. Therefore, fewer women need to be
treated to prevent one case of eclampsia for severe pre-eclampsia, than for nonsevere pre-eclampsia. Few women in this review had mild pre-eclampsia, as the
non-severe category primarily includes women with moderate disease. The number
of women who would need to be treated to prevent one case of eclampsia is likely
to be considerably higher for mild pre-eclampsia. Although unpleasant side effects
are common with magnesium sulphate, toxicity is rare. Almost all these data are
based on a 24-hour treatment regimen, clinical monitoring (of tendon reflexes,
respiratory rate and urine output), and either intramuscular maintenance therapy,
or an intravenous infusion of 1 g/hour. The reassurance about safety and lack of
serious side effects cannot, therefore, be extrapolated to higher doses, longer
duration or serum monitoring.
In the comparisons of magnesium sulphate with alternative agents, magnesium is
clearly better than either phenytoin or nimodipine. The remaining trials are too small
for any firm conclusions.

66 L. Duley

Table 2. Characteristics of trials evaluating anticonvulsants for women with eclampsia.

Trial

Methods

Participants

Interventions

Consecutively numbered sealed identical

treatment packs. Five
women excluded

Eclampsia: 54% allocated MgSO4 had anticonvulsant before entry,

as had 50% allocated
diazepam. 30% randomised after delivery

MgSO4: 4/5 g i.v. over 5 minutes.

Then either 10 g i.m. and 5 g every
4 hours for 24 hours or 1 g/hour
for 24 hours. For recurrent fits, 2 g
i.v. Diazepam: 10 mg i.v. bolus, then
40 mg in 500 ml for 24 hours. 20 mg
in 500 ml for a further 24 hours. For
recurrent fits, 10 mg i.v.

Randomly allocated,
no further details

105 women with

eclampsia and 13 with
imminent eclampsia.
For eclampsia, 44 allocated MgSO4 were
recruited before delivery, and 29 allocated
diazepam

MgSO4: 4-6 g i.v. Then 12 g/hour i.

v. 1 g if !55 kg, 2 g if O55 kg.
Diazepam: 1020 mg i.v. over 2
5 minutes. Then 2030 mg in
500 ml i.v. to keep woman drowsy
until delivery

Magnesium sulphate versus diazepam

Collaborative Trial
1995 (nZ
910)34

Egypt 1993
(nZ105)67

India 2001
(nZ100)57

Randomly distributed,
no further details

Eclampsia: 70 women in
first pregnancy and 79
recruited before delivery

MgSO4: 4 g in 25% MgSO4 over

10 minutes. 5 g i.m. 4 hourly until
24 hours after delivery or, if postpartum at randomisation, for
24 hours. Diazepam: 10 mg i.v.
bolus, 40 mg/500 ml i.v. for
24 hours. 20 mg/500 ml for a
further 24 hours. Then 10 mg i.m.,
changed when possible to oral. For
recurrent fits, 10 mg i.v.

Malaysia
1994 (nZ
11)54

Consecutive sealed
envelopes

Eclampsia

MgSO4: Pritchards regimen. Diazepam: not stated

Zimbabwe
1990 (nZ
51)58

Consecutively numbered sealed envelopes.

Blocks of 6, no stratification

Antepartum eclampsia:
R28 weeks, live fetus.
67% had diazepam
before entry; 71% of
those allocated MgSO4,
and 63% diazepam

Zimbabwe
1998 (nZ
69)59

Consecutively numbered sealed treatment

packs

Eclampsia: 40% of
women had already had
an anticonvulsant and
43% had delivered

MgSO4: 4 g i.v. over 35 minutes

and 10 g i.m. Then 5 g every 4 hours
for 24 hours. For recurrent fits, 2 g
i.v. Diazepam: 10 mg i.v. bolus, then
80 mg in 1 l for 24 hours. 40 mg in
1 l for a further 24 hours. For
recurrent fits, 10 mg i.v.
MgSO4: Either (a) 4/5 g i.v. over
5 minutes and 10 g i.m. Then 5 g i.m.
every 4 hours for 24 hours. Or (b)
4/5 g i.v. over 5 minutes, then 1 g/
hour for 24 hours. If recurrent fits
2 g i.v. Diazepam: 10 mg i.v. bolus.
Then infusion of 40 mg/500 ml for
24 hours. 20 mg/500 ml for next
24 hours. If recurrent fits, 10 mg i.v.
(continued on next page)

Evidence and practice: magnesium sulphate 67

Table 2 (continued)
Trial

Methods

Participants

Interventions

Collaborative Trial
1995 (nZ
777)34

Consecutively numbered sealed identical

treatment packs. Two
women lost to follow
up

Eclampsia: 76% allocated MgSO4 had anticonvulsant before trial

entry, and 80% allocated phenytoin. 19%
postpartum centres in
South Africa and India

India 1999
(nZ50)60

Sealed envelopes.
Sequence generated by
computer

Eclampsia: 29 women
had an anticonvulsant
before entry

South
Africa 1990
(nZ22)61

Random number tables

Antepartum eclampsia.
No prior anticonvulsant

South
Africa 1996
(nZ24)62

Computer-generated
random numbers in
sealed envelopes

Eclampsia

USA-Maryland 1993
(nZ2)63

Sealed opaque envelopes

USA-Memphis 1995
(nZ24)64

Randomly allocated

MgSO4: 4/5 g i.v. over 5 minutes.

Then, either 10 g i.m. and 5 g every
4 hours for 24 hours or 1 g/hour
for 24 hours. For recurrent fits, 2 g
i.v. Phenytoin: 1 g i.v. over 20 minutes, then 100 mg every 6 hours for
24 hours. For fits, diazepam 10 mg
MgSO4: 4 g i.v.C8 g i.m. Then 4 g i.
v. 4 hourly, until 24 hours after
delivery. Phenytoin: 15 mg/kg at
50 mg/min10 mg/kg initially then
5 mg/kg 2 hours later. 500 mg i.v.
12 hours later. Then 250 mg either
i.v. or oral, 12 hourly for 4 doses. All
women: 10 mg diazepam i.v. for fits,
5 mg nifedipine sl at entry
MgSO4: 4 g i.v. over 2030 minutes,
then 12 g/hour for 24 hours. Phenytoin: 500 or 1000 mg i.v. at max
50 mg/minute. Then 500 mg over
4 hours, 12 hours later, 500 mg
over 4 hours. All had clonazepam at
trial entry
MgSO4: 4 g i.v. and 10 g i.m.
Phenytoin: 1 g in 200 ml over 15
20 minutes. Both described as
loading dose only
MgSO4: 6 g i.v. bolus then infusion of
2 g/hour. Phenytoin: infusion of
1000, 1250, or 1500 mg
MgSO4: 6 g i.v. over 15 minutes,
then 2 g/hour to keep serum levels
4.89.6 mg/dl. Phenytoin: 1-1.5 g i.v.
Additional doses to keep serum
levels 1020 m/ml

Magnesium sulphate versus phenytoin

Antepartum eclampsia
(103 with PE included in
PE review)
Eclampsia: 9 women
allocated MgSO4 and 5
phenytoin had MgSO4
before trial entry. 79%
not delivered

Magnesium sulphate versus lytic cocktail

India 1994
(nZ91)65

Sealed, numbered, opaque envelopes in blocks

of 8. One woman
excluded

Eclampsia

MgSO4: 4 g i.v.C8 g i.m., then 4 g 4

hourly until 24 hours after delivery.
If recurrent fits, 1.5 g i.v. Lytic
cocktail: pethidine, promethazine
and chlorpromazine as described
by Menon

(continued on next page)

68 L. Duley

Table 2 (continued)
Trial

India 1995
(nZ108)66

Methods

Randomly allocated.
No other information

Participants

Interventions

Eclampsia

MgSO4: 4 g i.v.C10 g i.m. loading

dose, then 5 g 4 hourly up to
24 hours after delivery. Lytic cocktail: 100 mg pethidineC25 mg
chlorpromazine i.v. and 50 mg
chlorpromazineC25 mg promethazine i.m. 100 mg pethidine i.v. over
24 hours, 25 mg promethazine 4
hourlyC50 mg chlorpromazine 8
hourly for 48 hours i.m.

i.m., intramuscular; i.v., intravenous; MgSO4, magnesium sulphate; PE, pre-eclampsia; sl, sublingual.

CONTROLLING THE ACUTE CONVULSION AND PREVENTING

RECURRENCE OF ECLAMPSIA
When a woman has eclampsia, the immediate question is how best to control the acute
fit. Once the first fit has subsided, the next question is how best to reduce the risk of
her having further fits.
Currently, immediate care for women with eclampsia is to give a loading dose of
anticonvulsant. If the woman is still fitting this will, usually, control the acute fit. It also
ensures therapeutic levels are achieved rapidly. Maintenance therapy is then started,
with the aim of reducing the risk of further fits. This is usually continued for 24 hours,
although some advocate continuing until 24 hours after delivery. The choice of
anticonvulsant has been controversial but magnesium sulphate is now the drug of
choice.34,38
Systematic reviews have compared magnesium sulphate with diazepam39, phenytoin40 and lytic cocktail.41 Methods for these reviews are described in detail
elsewhere.3941 In brief, they include trials (Table 2) comparing alternative anticonvulsant regimens for eclampsia regardless of whether the first fit was before or after
delivery, whether the pregnancy was singleton or multiple, and irrespective of whether
an anticonvulsant had been given before trial entry.
Magnesium sulphate versus diazepam
Seven trials (1441 women) compared magnesium sulphate with diazepam. Magnesium
sulphate is associated with a reduction in the risk of maternal death compared to
diazepam, although the confidence intervals are wide (RR 0.59, 95% CI 0.370.94). For
recurrence of convulsions, there is a substantial reduction in risk associated with
magnesium sulphate (RR 0.44, 95% CI 0.340.57) (Figure 3). So, on an average, for every
seven women treated with magnesium sulphate rather than diazepam, one recurrence
of convulsions will be prevented (95% CI 610 women). There is no clear difference in
any other measure of maternal morbidity.
For the baby, the only statistically significant differences associated with the use of
magnesium sulphate, rather than diazepam, are a reduction in the risk of an Apgar score

Study
or sub-category

Magnesium
n/N

01 magnesium sulphate versus diazepam

Malaysia 1994
0/6
Egypt 1993
0/59
India 2001
0/60
Bangladesh 1998
5/100
Collab Trail 1995
60/453
Zimbabwe 1998
1/35
Zimbabwe 1990
5/24
Subtotal (95% Cl)
737
Total events: 71 (Magnesium), 162 (other)
Test for heterogeneity: Chi2=5.47, df=4(P=0.24),I2=26.8%
Test for overall effect: Z=6.34 (P<0.00001)

03 magnesium sulphate versus lytic cocktail

India 1995
3/51
India 1994
1/45
Subtotal (95% Cl)
96
Total events: 4 (Magnesium), 49 (Other)
2
Test for heterogeneity: Chi =0.00, df=1(P=0.98),I2=0%
Test for overall effect: Z=4.88 (P<0.00001)

RR (fixed)
95% cl

RR (fixed)
95% cl

0/5
0/46
2/40
26/100
125/452
2/34
7/27
704

Not estimable
Not estimable
0.13 [0.01, 2.73]
0.19 [0.08, 0.48]
0.48 [0.36, 0.63]
0.49 [0.05, 5.11]
0.80 [0.29, 2.20]
0.44 [0.34, 0.57]

4/11
10/25
2/13
66/387
1/11
447

0.11 [0.01, 1.85]

0.20 [0.05, 0.82]
0.23 [0.01, 4.40]
0.33 [0.21, 0.53]
0.85 [0.06, 12.01]
0.31 [0.20, 0.47]

38/57
11/45
102

0.09 [0.03, 0.27]

0.09 [0.01, 0.68]
0.09 [0.03, 0.24]

0.1

0.2

0.5

Favours magnesium

Favours control

Figure 3. Alternative anticonvulsants for eclampsia: effect on further fits.

10

Evidence and practice: magnesium sulphate 69

02 magnesium sulphate versus phenytoin

Siuth Africa 1990
0/11
India 1999
2/25
USA-Memphis 1995
0/11
Collab Trail 1995
22/388
South Africa 1996
1/13
Subtotal (95% Cl)
448
Total events: 25 (Magnesium), 83 (Control)
Test for heterogeneity: Chi2=1.56, df=4(P=0.82),I2=0%
Test for overall effect: Z=5.48 (P<0.00001)

other
n/N

70 L. Duley

!7 at 5 minutes (RR 0.72, 95% CI 0.550.94), and in length of stay in special care baby
nursery O7 days (RR 0.66, 95% CI 0.460.95.
Magnesium sulphate versus phenytoin
Six trials (897 women) compared magnesium sulphate with phenytoin. Magnesium
sulphate is associated with a 69% reduction in the relative risk of recurrent convulsions,
compared to phenytoin (RR 0.31, 95% CI 0.200.47) (Figure 3). On an average, for
every eight women treated with magnesium sulphate rather than phenytoin, one
recurrence of convulsions will be prevented (95% CI 613 women). The trend in
maternal mortality favours magnesium sulphate (RR 0.50, 95% CI 0.241.05).
Magnesium sulphate is also associated with a lower risk of pneumonia (RR 0.44, 95%
CI 0.240.79), ventilation (RR 0.66, 95% CI 0.490.90) and admission to an intensive
care unit (RR 0.67, 95% CI 0.500.89) than phenytoin.
Babies whose mothers were allocated magnesium sulphate, rather than phenytoin,
had fewer admissions to a special care baby unit (RR 0.73, 95% CI 0.580.91) and fewer
died or were in special care for O7 days (RR 0.77, 95% CI 0.630.95).
Magnesium sulphate versus lytic cocktail
Two trials (199 women) compared magnesium sulphate with lytic cocktail, usually a
mixture of chlorpromazine, promethazine and pethidine. Magnesium sulphate is
substantially better for preventing further fits than lytic cocktail (RR 0.09, 95% CI
0.030.24; RD 0.43, 95% CI K0.53 to K0.34; NNT 3, 95% CI 23) (Figure 3).
Although magnesium sulphate is associated with fewer maternal deaths than lytic
cocktail, the numbers are small and the difference is not statistically significant (RR
0.25, 95% CI 0.041.43). Both trials report data on respiratory depression, the risk
of which was reduced with magnesium sulphate (RR 0.12, 95% CI 0.020.91).
There were no cases of respiratory depression in the magnesium sulphate group
(0/96 versus 8/102). Other measures of maternal morbidity were reported by only
one trial.
Discussion
Magnesium sulphate is the drug of choice for women with eclampsia. There is
strong evidence that it is better than either diazepam or phenytoin, and reasonable
evidence that it is preferable to lytic cocktail. Women allocated magnesium
sulphate had magnesium sulphate for treatment of the acute fit, for maintenance
therapy and for control of any recurrence. It has been argued that diazepam
should be used for control of the acute fit42, but this view is not supported by
evidence.43
In these trials, women allocated magnesium sulphate for treatment of eclampsia
largely had the same regimens as those discussed above for pre-eclampsia; loading dose
of 4 g i.v., and then either intramuscular injections or an infusion of 1 g/hour, continued
for 24 hours, with clinical monitoring. Higher dose or longer duration are unlikely to
confer greater benefit but would almost certainly be associated with more side effects
and a greater risk of toxicity.

Evidence and practice: magnesium sulphate 71

CONCLUSIONS
After decades of dispute about whether to use an anticonvulsant for prophylaxis of
eclampsia, and which one to use for treatment of eclamptic fits, both these issues have
been resolved.44 This achievement is due largely to the collaboration of women,
clinicians and researchers in the conduct of two large randomised trials: one involved
1687 women and their carers in 27 hospitals in nine developing countries34, the other
10 141 women (85% from developing countries) and their carers in 175 hospitals in 33
countries.33 Thanks to their collective efforts, we now have reliable evidence that
magnesium sulphate can both prevent and control eclamptic convulsions. Medical,
midwifery or nursing staff, provided they are appropriately trained, can perform the
administration and clinical monitoring of magnesium sulphate. As this is an inexpensive
drug, it is especially suitable for use in low-income countries: it is time for concerted
action to ensure that women all over the world benefit from the results of the
important research on magnesium sulphate.44

Practice points
magnesium sulphate is the anticonvulsant of choice for women with eclampsia
magnesium sulphate should be considered for women with pre-eclampsia for
whom there is concern about the risk of eclampsia
intravenous administration is preferable, as side effects and injection site
problems seem lower
duration of treatment should not normally exceed 24 hours and if maintenance
therapy is by intravenous infusion this should not exceed 1 g/hour
women should have clinical monitoring before and during treatment
whether a loading dose of magnesium sulphate should be used at primary care
level before transfer to hospital is unclear. Other factors in this decision are
likely to include how long it will take to get the woman to hospital, how ill she is
and what support is available during transfer

Research agenda

what is the minimum effective dose of magnesium sulphate?

when is the optimal time to start prophylaxis?
what is the role of magnesium sulphate at the primary care level?
is magnesium sulphate for prevention of pre-eclampsia cost effective?
what are the long-term consequences of exposure for the mother and her
child?
any new agents for the prophylaxis or treatment of eclampsia should be
compared with magnesium sulphate in large randomised trials before being
introduced into clinical practice
theories about the pathogenesis of eclampsia need to take account of these
data

72 L. Duley

REFERENCES
1. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy.
Geographic variation in the incidence of hypertension in pregnancy. Am J Obstet Gynecol 1988; 158: 8083.
2. Crowther CA. Eclampsia at Harare Maternity Hospital. An epidemiological study. S Afr Med J 1985; 68:
927929.
3. Bergstrom S, Povey G, Songane F & Ching C. Seasonal incidence of eclampsia and its relationship to
meteorological data in Mozambique. J Perinat Med 1992; 20: 153158.
4. Douglas KA & Redman CW. Eclampsia in the United Kingdom. BMJ 1994; 309: 13951400.
*5. Mahler H. The safe motherhood initiative: a call to action. Lancet 1987; 1: 668670.
6. Rosenfield A & Maine D. Maternal mortalitya neglected tragedy. Where is the M in MCH? Lancet 1985;
2: 8385.
7. World Health Organization and UNICEF. Revised 1990 Estimates of Maternal Mortality. Geneva: WHO;
1990.
*8. The National Institute for Clinical Excellence, The Scottish Executive Health Department, The
Department of Health Social Services and Public Safety Northern Ireland. Why Mothers Die 19971999:
The Fifth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. London: RCOG
Press; 2001.
9. Chalmers I & Grant A. Salutary lessons from the Collaborative Eclampsia Trial. Evidence-Based Med 1996;
1: 3940.
10. Chesley LC. A short history of eclampsia. Obstet Gynecol 1974; 43: 559602.
11. Loudon I. Death in Childbed: An International Study of Maternal Care And Maternal Mortality 18001950.
Oxford: Clarendon Press; 1992.
12. Chesley L. Survey of management and case fatality. In Chesley L (ed.) Hypertensive disorders of pregnancy.
New York: Appelton Century Crofts, 1978, pp. 309340.
13. Eden TW. Eclampsia: a commentary on the reports presented to the British Congress of Obstetrics and
Gynaecology, June 29th 1922. J Obstet Gynaecol Br Emp 1922; 29: 386401.
14. Stroganoff W & Davidovitch O. Two hundred cases of eclampsia treated with magnesium sulphate. A
preliminary report. J Obstet Gynaecol 1937; 44: 289299.
15. Lazard EM. A preliminary report on the intravenous use of magnesium sulphate in puerperal eclampsia.
Am J Obstet Gynecol 1925; 9: 178188.
16. Dorsett L. The intramuscular injection of magnesium sulfate for the control of convulsions in eclampsia.
Am J Obstet Gynecol 1926; 11: 227231.
17. Lazard EM. An analysis of 575 cases of eclamptic and pre-eclamptic toxemias treated by intravenous
injections of magnesium sulphate. Am J Obstet Gynecol 1933; 26: 647656.
18. Irving FC. The treatment of eclampsia by plasmaphaeresis. N Engl J Med 1930; 203: 10701072.
19. Gifford R, August P, Chesley L et al. National high blood pressure education program working group
report on high blood pressure in pregnancy. Am J Obstet Gynecol 1990; 163: 16911712.
20. Pritchard JA & Pritchard SA. Standardized treatment of 154 consecutive cases of eclampsia. Am J Obstet
Gynecol 1975; 123: 543552.
21. Pritchard JA, Cunningham FG & Pritchard SA. The Parkland Memorial Hospital protocol for treatment of
eclampsia: evaluation of 245 cases. Am J Obstet Gynecol 1984; 148: 951963.
22. Sibai BM. Magnesium sulfate is the ideal anticonvulsant in preeclampsiaeclampsia. Am J Obstet Gynecol
1990; 162: 11411145.
23. Eastman NJ & Steptoe PP. The management of preeclampsia. Can Med Assoc J 1945; 52: 562568.
24. Zuspan FP. Problems encountered in the treatment of pregnancy-induced hypertension. A point of view.
Am J Obstet Gynecol 1978; 131: 591597.
25. Pritchard JA. The use of the magnesium ion in the management of eclamptogenic toxemias. Surg Gynecol
Obstet 1955; 100: 131140.
26. Belfort MA & Moise Jr. KJ. Effect of magnesium sulfate on maternal brain blood flow in preeclampsia: a
randomized, placebo-controlled study. Am J Obstet Gynecol 1992; 167: 661666.
27. Sadeh M. Action of magnesium sulfate in the treatment of preeclampsiaeclampsia. Stroke 1989; 20: 1273
1275.

Evidence and practice: magnesium sulphate 73

28. Goldman RS & Finkbeiner SM. Therapeutic use of magnesium sulfate in selected cases of cerebral
ischemia and seizure. N Engl J Med 1988; 319: 12241225.
29. Nelson KB & Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight
infants? Pediatrics 1995; 95: 263269.
30. Scudiero R, Khoshnood B, Pryde PG et al. Perinatal death and tocolytic magnesium sulfate. Obstet Gynecol
2000; 96: 178182.
31. Grether J, Hoogstrate J, Selvin S & Nelson KB. Magnesium sulphate tocolysis and risk of neonatal death.
Am J Obstet Gynecol 1998; 178: 16.
*32. Crowther C, Hiller J, Doyle L, Haslam R & for the Australasian Collaborative Trial of Magnesium Sulphate
(ACTOMgSO4) Collaborative Group. Effect of magnesium sulfate given for neuroprotection before
preterm birth. JAMA 2003; 290: 26692676.
*33. Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium
sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002; 359: 18771890.
*34. Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the
Collaborative Ecampsia Trial. Lancet 1995; 345: 14551463.
35. Roberts JM, Villar J & Arulkumaran S. Preventing and treating eclamptic seizures. Magnesium sulphate is
effective and recommended for use. BMJ 2002; 325: 609610.
*36. Duley L, Gulmezoglu AM & Henderson-Smart DJ. Magnesium sulphate and other anticonvulsants for
women with pre-eclampsia. The Cochrane Library12003;: CD000025.
37. Magpie Trial Follow Up Study Management Group. The Magpie Trial Follow Up Study: outcome after
discharge from hospital for women and children recruited to a trial comparing magnesium sulphate with
placebo for pre-eclampsia [ISRCTN86938761]. BMC Pregnancy and Childbirth 2004; 4(5).
38. Robson SC. Magnesium sulphate: the time of reckoning. Br J Obstet Gynaecol 1996; 103: 99102.
*39. Duley L & Henderson-Smart D. Magnesium sulphate versus diazepam for eclampsia. The Cochrane Library
2004; 1: CD000127.
*40. Duley L & Henderson-Smart D. Magnesium sulphate versus phenytoin for eclampsia. The Cochrane Library
2004; 1: CD000128.
*41. Duley L & Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. The Cochrane Library
2004; 1: CD002960.
42. Fox R & Draycott T. Prefer diazepam for initial control of pre-eclamptic fits. BMJ 1995; 311: 1433.
43. Duley L. Magnesium sulphate should be used for eclamptic fits. BMJ 1996; 312: 639.
*44. Sheth SS & Chalmers I. Magnesium for preventing and treating eclampsia: time for international action.
Lancet 2002; 359: 18721873.
45. 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: 300303.
46. Moodley J & Moodley J. Prophylactic anticonvulsant therapy in hypertensive crises of pregnancythe
need for a large randomized trial. Hypertens Pregnancy 1994; 13: 245252.
47. Chen F, Chang S & Chu KK. Expectant management in severe preeclampsia: does magnesium sulfate
prevent the development of eclampsia. Acta Obstet Gynecol Scand 1995; 74: 181185.
48. Witlin A, Friedman S & Sibai B. The effect of magnesium sulfate therapy on the duration of labor in women
with mild preeclampsia at term: a randomized double-blind, placebo-controlled trial. Am J Obstet Gynecol
1997; 176: S15.
49. Livingston J, Livingston L, Ramsey R et al. Magnesium sulfate in women with mild preeclampsia: a
randomised controlled trial. Obstet Gynecol 2003; 217220.
50. Lucas M, Leveno K & Cunningham M. A comparison of magnesium sulfate with phenytoin for the
prevention of eclampsia. New Engl J Med 1995; 333: 201205.
51. Atkinson M, Guinn D, Owen J & Hauth J. Does magnesium sulfate affect the length of labor induction in
women with pregnancy-associated hypertension? Am J Obstet Gynecol 1995; 173: 12191222.
52. Friedman S, Kee-Hak L, Baker C & Repke J. Phenytoin versus magnesium sulphate in pre-eclampsia: a pilot
study. Am J Perinatol 1993; 10: 233238.
53. Walss RR & Levario A. Anticonvulsant treatment of severe pre-eclampsia: comparison of diazepam and
magnesium sulfate. Gynecol Obstet Mexico 1992; 60: 331335.
54. Adeeb N, Hatta A & Shariff J. Comparing magnesium sulphate to diazepam in managing severe preeclampsia and eclampsia. Proceedings of 10th World Congress International Society for the Study of
Hypertension in Pregnancy 1996; 246.

74 L. Duley
55. Belfort M, Anthony J, Saade G, Allen J & for tNSG. A comparison of magnesium sulfate and nimodipine for
the prevention of eclampsia. N Engl J Med 2003; 348: 304311.
56. Rudnicki M, Frolich A, Pilsgaard K et al. Sanchez Mea. Comparison of magnesium and methyl dopa for the
control of blood pressure in pregnancies complicated with hypertension. Gynecol Obstet Invest 2000; 49:
231235.
57. Rani M, Sharma D, Prakash A. Maternal and perinatal outcome in eclampsia: diazepam vs magnesium
sulphate regimen (a prospective trial). Personnal Communication.
58. Crowther C. Magnesium sulphate versus diazepam in the management of eclampsia: a randomized
controlled trial. Br J Obstet Gynaecol 1990; 97: 110117.
59. Duley L & Mahomed K. Magnesium sulphate in eclampsia. Lancet 1998; 351: 10611062.
60. Sawhney H, Sawhney I, Mandal R et al. Efficacy of magnesium sulphate and phenytoin in the management
of eclampsia. J Obstet Gynaecol Res 1999; 25: 333338.
61. Dommisse J. Phenytoin sodium and magnesium sulphate in the management of eclampsia. Br J Obstet
Gynaecol 1990; 97: 104109.
62. Naidu S, Payne A, Moodley J et al. Randomised study assessing the effect of phenytoin and magnesium
sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound. Br J Obstet
Gynaecol 1996; 103: 111116.
63. Friedman S, Lim K, Baker C & Repke J. Phenytoin vs magnesium sulfate in preeclampsia: a pilot study. Am
J Perinatol 1993; 10: 233238.
64. Friedman S, Schiff E, Kao L & Sibai B. Phenytoin versus magnesium sulfate in patients with eclampsia:
preliminary results from a randomized trial. Am J Obstet Gynecol 1995; 172: 384.
65. Bhalla A, Dhall G & Dhall K. A safer and more effective treatment regimen for Eclampsia. Aust N Z J Obstet
Gynaecol 1994; 34: 144148.
66. Jacob S, Gopalakrishnan K & Lalitha K, Standardised clinical trial of magnesium sulphate regime in comparison
with M.K.K. Menons lytic cocktail regime in the management of eclampsia Proceedings of the 27th British
Congress of Obstetrics and Gynaecology, 47 July 1995, Dublin 1995 p. 303.
67. Sayed EH, Sayed GH, Abdel Aal DM et al, A comparative trial of magnesium sulphate and diazepam in the
management of eclampsia Proceedings of 10th Annual Scientific Conference of Assiut Faculty of Medicine April
1993.