International Journal of Gynecology and Obstetrics 132 (2016) 6871

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International Journal of Gynecology and Obstetrics

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CLINICAL ARTICLE

Maternal outcomes after 12 hours and 24 hours of magnesium sulfate

therapy for eclampsia
Shaheen Anjum , Namarata Goel, Rajyashri Sharma, Zehra Mohsin, Nidhi Garg
Department of Obstetrics and Gynecology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To assess the effectiveness of a reduced duration (12 hours) of magnesium sulfate (MgSO4) adminis-
Received 14 January 2015 tration for eclampsia. Methods: In a prospective randomized study, women with eclampsia (prepartum,
Received in revised form 16 June 2015 intrapartum, or postpartum) attending Jawaharlal Nehru Medical College, Aligarh, India, between January
Accepted 30 September 2015 2012 and September 2013 were enrolled. The inclusion criteria were blood pressure of at least 140/90 mm Hg
after 20 weeks, proteinuria (dipstick value + 1), and seizures not attributed to other causes. Participants
Keywords:
were assigned to control and study groups according to the time of enrollment (6-month blocks). All patients re-
Convulsions
Eclampsia
ceived a MgSO4 loading dose (4 g, intravenously), followed by maintenance doses (1 g/hour) for 12 hours (study
Magnesium sulfate group) and 24 hours (control group). The primary outcome was recurrent convulsions after completion of MgSO4
therapy. Patients with treatment failure were excluded from analyses. Results: Analyses included 132 patients
in the study group and 72 patients in the control group. No convulsions recurred in either group after the com-
pletion of treatment. Conclusion: For women with eclampsia, 12 hours of magnesium sulfate could effectively
prevent recurrent convulsions.
2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction instead of 24 hours after the last t or delivery is effective in improving

Eclampsia is an important cause of maternal morbidity and mortali-
ty, especially in low-resource countries. Together, pre-eclampsia and
eclampsia account for 40 000 maternal deaths worldwide every year
[1]. In India, these conditions account for 5% of all maternal deaths [1].
The accepted therapeutic management includes: prevention of
seizures; adequate control of blood pressure; stabilization of cardiovas-
cular, renal, and electrolyte status; and prompt delivery. Administration
of magnesium sulfate (MgSO4) for 24 hours after the last t or delivery
(whichever is later) is considered best empirical practice, but it has
not been properly subjected to scientic scrutiny [2]. Decreasing the
duration of MgSO4 infusion would benecial to both the patient
and healthcare systems. One randomized controlled trial [3] showed
that seizures can be effectively controlled in cases of eclampsia by
giving only a loading dose of MgSO4: the recurrent convulsion rate
was found to be almost the same among patients who received the
loading dose (3.96%) and among those who received the standard reg-
imen (3.51%; P N 0.05).
The aim of the present study was therefore to determine whether
decreasing the duration of the intravenous MgSO4 regimen to 12 hours
Corresponding author at: Department of Obstetrics and Gynecology, Jawaharlal Nehru
Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002,
India. Tel.: +91 9319861442; fax: +91 01123844992.
E-mail address: shahanjum73@gmail.com (S. Anjum).
maternal outcome in eclampsia.
2. Materials and methods
In the present prospective randomized study, women with eclamp-
sia attending the Department of Obstetrics and Gynecology at Jawaharlal
Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh,
India, were enrolled between January 1, 2012, and September 30, 2013.
The inclusion criteria were: prepartum, intrapartum, or postpartum
eclampsia with a blood pressure of 140/90 mm Hg or higher after
20 weeks of pregnancy; proteinuria with a dipstick value of + 1 or
higher; and seizures not attributed to other causes among women
with pre-eclampsia. The exclusion criteria were eclampsia with compli-
cations (e.g. acute renal failure, HELLP syndrome [hemolysis, elevated
liver enzymes, and low platelet count], or pulmonary edema) or associ-
ated maternal disease, contraindication to MgSO4 (e.g. drug hypersensi-
tivity, myasthenia gravis, anuria, or oliguria), prior intake of any other
anticonvulsant, and a history of epilepsy. The study was approved by
the Ethical Committee of the institution, and patients provided informed
consent before the administration of MgSO4.
Patients with eclampsia who were admitted during the study period
were randomly assigned to either the study group (12 h MgSO4) or
the control group (24 h MgSO4) as follows: patients admitted in the
rst 6 months were enrolled into the control group, and those admitted
in the next 6 months were enrolled into the study group. This alter-
nating pattern of enrollment was followed for the duration of study.

http://dx.doi.org/10.1016/j.ijgo.2015.06.056
0020-7292/ 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
 S. Anjum et al. / International Journal of Gynecology and Obstetrics 132 (2016) 6871
Participants were not told which group they had been assigned to, but
because the groups received treatments for different lengths of time,
full masking was not possible. Investigators and data analysts were
not masked to group assignment.
All women were examined at the time of admission and a detailed
history was taken. Complete blood counts, coagulograms, liver and
renal function tests, and urine protein measurements were performed.
Women in the study group were given a loading dose of 4 g of intra-
venous MgSO4, followed by a maintenance dose of 1 g per hour for
12 hours after the last t or delivery (whichever was later). Those in
the control group were given a loading dose of 4 g of intravenous
MgSO4, followed by a maintenance dose of 1 g per hour for 24 hours
after the last t or delivery.
All women were monitored for the entire duration of MgSO4 infu-
sion by trained obstetricians and gynecologists for blood pressure,
patellar reexes, respiratory rate, urine output, and reoccurrence of con-
vulsions. In the case of MgSO4 toxic effects, the plan of management was
to stop further infusions of MgSO4, to inject 1 g of calcium gluconate
(10 mL of 10% solution) intravenously, and to switch the therapy to
another anticonvulsant. These patients were considered to have treat-
ment failure. After completion of the MgSO4 infusion, patients were
monitored every 4 hours until normalization of blood pressure, and
then every 12 hours until discharge.
Labetalol was used as an antihypertensive drug as per the manage-
ment protocol of the study institute. The participants were induced,
allowed to undergo spontaneous labor, or underwent cesarean delivery
depending on the obstetric indication and the patients general condition.
The primary outcome was recurrent convulsions once the MgSO4
therapy was completed. If a repeat convulsion occurred before comple-
tion of therapy, the patient was infused with a 2 g loading dose of
MgSO4, and women in the study group were switched to a maintenance
dose of MgSO4 for 24 hours. If a second convulsion was observed during
the therapy, the treatment was switched from MgSO4 to phenytoin and
considered as an MgSO4 failure.
Secondary outcomes were related to patient recovery, which was
analyzed in terms of total dose of MgSO4 given, duration of hospital
stay, and duration of Foley catheterization. The patients were followed
up until discharge from hospital.
The study data were analyzed by SPSS version 21 (IBM, Armonk, NY,
USA). The study and control groups were compared by t test and 2 test
as appropriate. Patients with treatment failures were excluded from
analysis. P b 0.001 was considered signicant.
3. Results
During the study period, there were 5705 deliveries, among which
eclampsia was recorded in 223 (3.9%). All women with eclampsia
were monitored in the high dependency unit and transferred to the
intensive care unit if their general condition deteriorated. In a few
cases, the systolic blood pressure of the patients ranged from 130 to
140 mm Hg, but there were no cases of eclampsia without proteinuria.
There were 15 maternal deaths due to eclampsia, giving a case fatality
rate of 6.7%.
After the exclusion of 15 cases of complicated eclampsia, 208 patients
were included in the study (Fig. 1). There were 162 (77.9%) cases
of prepartum eclampsia, 7 (3.4%) of intrapartum eclampsia, and
39 (18.8%) of postpartum eclampsia. Among the study participants,
2 (1.0%) had a history of prenatal care, 146 (70.2%) came from a rural
background, 8 (3.8%) were literate, and 206 (99.0%) were unbooked.
Several of the patients who were referred to the study hospital had epi-
sodes of convulsions that were not witnessed by any member of the fam-
ily, although two to three episodes of convulsions before admission had
been the reported by relatives for most women (data not shown).
Among the study participants, 132 were assigned to the study group
and received the 12-hour regime of MgSO4, and 76 were assigned to the
control group and received the conventional 24-hour regime of MgSO4.
69
However, 10 patients in the control group had repeat convulsions
during the rst 2 hours of therapy. Six of these patients responded
to a repeat loading dose of 2 g of MgSO4 and then underwent
24 hours of MgSO4; the remaining four patients were switched to phe-
nytoin therapy. These four cases were categorized as treatment failures
and excluded from the study analysis. Thus, the failure rate of MgSO4
therapy was 1.9%.
Among the patients included in analyses, those in each of the two
groups were similar in terms of age, number of previous pregnancies,
and length of pregnancy (Table 1). In addition, systolic blood pressure,
diastolic blood pressure, and albuminuria on admission and at discharge
were similar in the two groups.
Regarding the primary outcome, no convulsions recurred in either
group after the completion of MgSO4 for 12 hours or 24 hours. Re-
garding the secondary outcomes, signicantly higher total amounts
of MgSO4, duration of Foley catheterization, and duration of monitoring
were noted in the control group when compared with the study group
(P b 0.001 for all) (Table 2). No patients developed complications attrib-
uted to eclampsia after admission.
Among a total of 169 deliveries after eclampsia onset, 79 (46.7%)
occurred vaginally and 90 (53.3%) by cesarean. Overall, 113 (66.9%)
had live births, 31 (18.3%) had intrauterine death, and 25 (14.8%) had
neonatal death. Apgar scores and admission to the neonatal intensive
care unit were not recorded.
Among patients with vaginal delivery, the mean duration of hospital
stay was 5.3 0.8 days in the study group as compared with 7.5
1.5 days in the control group (P b 0.001). A similar difference in the
mean duration of hospital stay was seen among patients who delivered
by cesarean (7.7 0.9 vs 10.5 1.5 days; P b 0.001).
No toxic effects of MgSO4 were noted in either group.
4. Discussion
In the present study, no convulsions were recorded after either
MgSO4 infusion for 12 hours or 24 hours after delivery or the last seizure
(whichever occurred later) among women with eclampsia. This nding
could represent a breakthrough in the management of patients with
eclampsia in low-resource nations where the incidence of this disorder
is high and puts an increased burden on health care.
The incidence of eclampsia was 3.9% in the present study, which is
higher than previously reported values of 0.7%, 0.87%, and 3.2% [46].
The incidence of eclampsia in the present study might be higher because
the study was conducted in a referral center for a large rural population
where patients are often admitted at a complicated stage of labor, which
might also be responsible for the high case fatality rate (6.7%). Notably,
99% of the study participants were unbooked or unregistered. It was
noted as far back as 1952 that eclampsia would be a clinical rarity if
effective prenatal care were made available [7].
Previous studies have assessed the minimum amount and duration
of MgSO4 for preventing recurrent convulsions in cases of eclampsia.
For example, in a large study on low-dose MgSO4, Sardesai et al. [8] re-
ported that convulsions were controlled in 94% of cases of eclampsia.
Similarly, Begum et al. [3] reported that eclamptic convulsions were
controlled in 98% of women treated with a modied (Dhaka) regime
of MgSO4.
In the present study, 10 patients had repeat convulsions during the
rst 2 hours of therapy. Six of them responded to a repeat loading
dose of 2 g MgSO4, but four were switched to phenytoin in accordance
with the protocol of the hospital. After completion of therapy, no re-
current convulsions occurred in either group. To our knowledge,
there are no previous data on the recurrence of convulsions after the
completion of 24 hours of therapy. In the present study, patients
who had repeat convulsions in the rst 2 hours of therapy were rou-
tinely given 24 hours of MgSO4. Further studies are needed to deter-
mine the effects of decreasing the dose and duration of MgSO4 in
complicated eclampsia cases.
70 S. Anjum et al. / International Journal of Gynecology and Obstetrics 132 (2016) 6871

Total deliveries
(n=5705)

Women without eclampsia

(n=5482)

Women with
eclampsia (n=223)

Complicated cases (n=15)

Uncomplicated
cases (n=208)

Assigned to receive Assigned to receive

12 h MgSO4 (n=132) 24 h MgSO4 (n=76)

Repeat convulsion
during therapy (n=10)

Responded to 2 g Treatment failure

loading MgSO4 (n=6) (n=4)a

Analyzed (n=132) Analyzed (n=72)

Fig. 1. Flow of participants through the study. a Treatment failure was dened as more than two episodes of convulsions despite treatment with magnesium sulfate.

In the present study, the mean duration of monitoring was 19.3 Early Foley catheter removal has substantial advantages for the early
4.9 hours in the 12-hour group as compared with 31.8 4.7 hours in mobilization of a patient, and indicates better bladder function. The
the 24-hour group. This reduction will be benecial at the level of mean duration of Foley catheterization in the present study was
tertiary-care centers, district hospitals, and primary healthcare centers 19.6 hours in the 12-hour group as compared with 31.5 hours in the
in many low-resource countries. It will reduce the burden on the 24-hour group.
healthcare staff and allow appropriate motherchild bonding. The Among patients with vaginal delivery, the mean duration of hospital
mean amount of MgSO4 administered was 23.2 2.8 g in the 12-hour stay was 5.3 days in the study group as compared with 7.5 days in the
group as compared with 34.9 3.2 g in the 24-hour group. In the control group. A similar reduction in hospital stay was seen among pa-
Collaborative Eclampsia Trial [9], the mean dose of MgSO4 was 38 tients who had cesarean delivery (7.7 days vs 10.7 days). A shortened
9.7 g, which is similar to that seen in the 24-hour group in the present hospital stay is benecial for both patients and healthcare centers
study. The lower dose of MgSO4 administered in the 12-hour group because it decreases the overall cost of treatment, reduces unnecessary
would safeguard patients against MgSO4 toxic effects. exposure to nosocomial infections, and allows better utilization of
available health resources.
Some limitations of the present study should be noted. There were
Table 1 no prespecied criteria for the assessment of the advantages of early
Baseline characteristics.a mobilization. Additionally, a Foley tip culture could have been analyzed
Characteristic 12 h MgSO4 24 h MgSO4 to quantitatively assess the reduction in the risk of urinary tract infec-
(n = 132) (n = 76) tion as a result of early removal of the Foley catheter.
On admission
Maternal age, y 23.8 3.4 24.5 3.6
Gravidity Table 2
1 94 (71.2) 60 (78.9) Secondary outcomes.a
24 30 (22.7) 14 (18.4)
Outcome 12 h MgSO4 24 h MgSO4 t value P value
5 8 (6.1) 2 (2.6)
(n = 132) (n = 72)
Length of pregnancy, wk 35.6 1.2 36.5 1.6
Systolic blood pressure, mm Hg 166.7 18.8 161.6 21.5 Total amount of MgSO4, g 23.2 2.8 34.9 3.2 24.9 0.001
Diastolic blood pressure, mm Hg 102.2 8.7 99.7 9.7 Duration of Foley catheterization, h 19.6 2.5 31.5 3.2 27.6 0.001
Proteinuria, dipstick value 2.97 0.4 2.77 0.7 Duration of monitoring, h 19.3 4.9 31.8 4.7 16.2 0.001
On discharge Hospital stay
Mean systolic blood pressure, mm Hg 126.6 7.6 125.4 8.0 Vaginal delivery, d 5.3 0.8 7.5 1.5 8.1 0.001
Mean diastolic blood pressure, mm Hg 86.4 3.5 84.8 5.0 Cesarean delivery, d 7.7 0.9 10.5 1.9 9.0 0.001

Abbreviation: MgSO4, magnesium sulfate. Abbreviation: MgSO4, magnesium sulfate.

a a
Values are given as mean SD or number (percentage). Values are given as mean SD unless indicated otherwise.
 S. Anjum et al. / International Journal of Gynecology and Obstetrics 132 (2016) 6871
In summary, 12 hours of MgSO4 therapy was found to be effective in
preventing recurrent convulsions among women with eclampsia. The
lower dose led to shorter durations of monitoring and catheterization,
and shorter hospital stays, which are important considerations in the
provision of health care in low-resource countries.
Conict of interest
The authors have no conicts of interest.
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