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OJHAS Vol. 9, Issue 4:
(Oct-Dec, 2010) |
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| Should Magnesium
Sulphate Prophylaxis be Used in all Cases of Severe Preeclampsia? |
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Sohini Bhattacharya, Associate Professor, Dept of Obstetrics and Gynecology,
Animesh Naskar, Assistant Professor, Dept of Obstetrics and Gynecology,
Sukanta Mondal, Assistant Professor,
Dept of Community Medicine,
Ajanta Samanta, Post Graduate Trainee, Dept of Obstetrics and Gynecology,
Pati Shyama Pada,
Professor and Head, Dept of Obstetrics and Gynecology,
North Bengal Medical College, Shushrutanagar, Darjeeling, India. |
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Address For Correspondence |
76, Rashbehari Sarani,
Khelaghar
More,
Hakimpara, Siliguri,
Darjeeling -734001,
West Bengal, India.
E-mail:
drsohinibhattacharya@yahoo.co.in |
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Bhattacharya S, Naskar A, Mondal S, Samanta A, Pati SP. Should Magnesium
Sulphate prophylaxis be used in all cases of severe preeclampsia?
Online J Health Allied Scs.
2010;9(4):12 |
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Submitted: Nov 27,
2010; Accepted: Dec 28, 2010; Published: Jan 20, 2011 |
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| Abstract: |
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A case control study, undertaken
in the department of Obstetrics and Gynecology in a tertiary referral
centre, was designed to administer standard dose of magnesium sulphate
to 50 randomly selected severely preeclamptic women in labor (Group
1). 48 women who formed the control group did not receive the drug (Group
2). The admission – delivery interval, rate of Cesarean section showed
no statistically significant difference. Four patients developed convulsions
in Group 1 in contrast to twelve patients in Group 2. Efficacy of magnesium
sulphate at preventing eclampsia was calculated as 68%. Mild respiratory
depression occurred in two cases and oliguria in eight cases in Group
1. Both the conditions improved on suspending further doses of magnesium
sulphate. No patient had post partum haemorrhage in Group 1 although
4% patients had it in Group 2. Neonatal outcome was comparable in both
the groups. Hence magnesium sulphate may be regarded as a fairly safe
and effective prophylactic agent for eclampsia when used in severe preeclampsia
in labor.
Key Words:
Preeclampsia;
Prophylactic magnesium sulphate
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Eclampsia is regarded as one
of the most dangerous complications of preeclampsia and accounts for
most of the maternal deaths in our country. Since the pathogenesis of
eclampsia is not exactly known, the strategies for prevention are limited.
Anticonvulsants are given to women with preeclampsia with the belief
that they will prevent the onset of eclampsia and so improve the outcome
for both mother and baby. Magnesium sulphate is a significantly better
drug than either Diazepam or phenytoin for preventing recurrent seizures
in eclamptic patients and is now considered as the drug of choice in
treating eclampsia.(1) Magnesum sulpate has diverse cardiovascular
and neurological effects. It alters calcium metabolism and crosses the
placental barrier too. It has also to be kept in mind that even if eclampsia
is prevented, it does not mean that other serious complications of preeclampsia
can be avoided with this drug.(2) Hence the risk-benefit ratio has
to be judged before routine administration of this drug in all women
with preeclampsia. It is recommended that individual units determine their own
protocols and monitor outcomes.(3)
Objective of the
study: To determine the efficacy and safety of magnesium sulphate
in preventing the development of eclampsia in the severely preeclamptic
patients in labor.
The study was undertaken from
March 2009 to February 2010 in the department of Obstetrics and Gynecology
of our institution which is a tertiary referral centre catering to four
northern districts of West Bengal. The design of the study was an analytical
case control type. Patients with severe preeclampsia, with blood pressure
above 159/109mm of mercury were taken for the study. 50 patients were
randomly selected to receive magnesium sulphate. We used Pritchard’s
protocol by which a loading dose of 4g was given intravenously followed
by intramuscular dose of 5g in each buttock. 5g of intramuscular dose
was repeated every four hours upto 24 hours after delivery. 48 women
who formed the control group, did not receive this drug. Hypertension
was controlled with IV labetalol in either group. Both the study
and control group were monitored for the duration of labor, mode of
delivery, maternal complications like convulsions, respiratory depression,
oliguria, hematuria, postpartum hemorrhage, and fetal outcome was judged
by the Apgar score at five minutes of birth and duration of stay at
neonatal care unit (NICU).
Statistical analysis: All statistical analyses are
done by the SPSS software version 17. Comparison between maternal demographic
profiles and maternal and neonatal outcome between the two groups is
done by Chi-Square test.
Table 1 shows that both the
study and control groups were comparable as regards their age, gravida,
gestational age on admission and duration of hypertension. Table 2 shows
there doesn’t seem to be any significant prolongation of labor in
the study group in comparison to the control group, since the admission
delivery interval are similar. 50% (25 out of 50) of women in Group
1 had a vaginal delivery out of which 20% (10 women) had forceps application.
In contrast, in Group 2, out of the 45.2% (22 women) who had vaginal
delivery, 4.2% (2 women) needed forceps applications. (p<0.05, Chi-Square
= 5.66). This difference seems to be significant statistically. The
incidence of Cesarean section was similar in both the groups – 50%
in Group 1 and 54.2% in Group 2. Indication of operative delivery as
labor dystocia, 22.85% in Group 1, which was more than Group 2, at 7.14%
is not statistically significant (Chi-Square=2.32,p>0.05). Fetal
distress occurred equally in both the groups (Chi-Square=0.75, p>0.05).
Four patients developed convulsions in Group 1 which is significantly
lower than in Group2 that had an incidence of convulsion in 12 patients
(Chi-Square=5.79,p<0.05). Mild respiratory depression occurred in
two cases and oliguria in 8 cases in the Group 1. The condition improved
in all cases by suspending further doses of magnesium sulphate. The
incidence of Apgar score 7-10 between Group1, at 40% and Group 2 at
47.9% is comparable (Chi-Square=o.62, p>0.05). Significantly more
neonates were having an Apgar score 3-6 in Group 1 than in Group 2,
32% versus 10.4% respectively (Chi-Square=6.78,p<0.01).
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Table 1: Comparison of socio-demographic
and antenatal variables between Group 1 and Group 2. |
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Group 1 |
Group 2 |
Total |
P value |
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Age group |
| 15-20 |
30 |
29 |
59 |
Chi-Square= 0.25
p>0.05 |
| 20-25 |
17 |
15 |
32 |
| >25 |
3 |
4 |
7 |
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Gravida
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| G1 |
38 |
40 |
78 |
Chi-Square= 0.24
p>0.05 |
| G2 |
11 |
8 |
19 |
| G3 |
1 |
0 |
1 |
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Gestational
age on admission |
| 28-36 weeks |
20 |
18 |
38 |
Chi-Square= 1.08
p>0.05 |
| 37-40 weeks |
27 |
28 |
55 |
| >40 weeks |
1 |
0 |
1 |
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Duration
of hypertension |
| <2 weeks |
2 |
3 |
5 |
Chi-Square= 3.06
p>0.05 |
| 2-4 weeks |
30 |
25 |
55 |
| >4 weeks |
2 |
0 |
2 |
| Unknown
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16 |
20 |
36 |
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Table2: Comparison of the different
obstetric outcome between Group 1 and Group 2. |
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Group1 (n=50) |
Group 2(n=48) |
Total |
P value |
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Admission
delivery interval (hours) |
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1-5 |
15 |
17 |
32 |
Chi-Square= 4.27
p>0.05 |
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6-10 |
17 |
10 |
27 |
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11-20 |
0 |
2 |
2 |
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16-20 |
5 |
7 |
12 |
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>20 |
13 |
12 |
25 |
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Mode
of delivery |
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Spontaneous
vaginal |
15 (30%) |
20 (41%) |
35 |
Chi-Square= 1.45 p>0.05 |
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Forceps application |
10 (20%) |
2 (4.2%) |
12 |
Chi-Square= 5.66 p<0.05 |
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Cesarean
section |
25 (50%) |
26 (54.2%) |
51 |
Chi-Square= 0.17 p>0.05 |
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Indication
of operative delivery (Forceps and Cesarean section) |
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Indications
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n= 35 |
n=28 |
Total |
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Uncontrolled
hypertension |
15 (42.8%) |
14(50%) |
29 |
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Uncontrolled
convulsion |
2 (5.7%) |
5 (17.8%) |
7 |
Chi-Square= 2.32 p>0.05 |
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Dystocia
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8 (22.8%) |
2(7.14%) |
10 |
Chi-Square= 2.88 p>0.05 |
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Fetal distress |
10 (28.5%) |
7 (25%) |
17 |
Chi-Square= 0.75 p>0.05 |
Incidence of Apgar score <3
appears to be higher in Group 2 (41.6%) than in Group1 (22.2%) but not
significantly (Chi-Square=0.08,p>0.05).
Efficacy of magnesium sulphate
for preventing the incidence of convulsion [=(Incidence of convulsion
among Group 2 - incidence of convulsion in Group
1) × 100/Incidence of convulsion in Group 2)] was calculated to be 68%. [(25-8)×100/25 = 68]
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Table 3: Maternal outcome in
Group 1 and Group 2 |
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Maternal
complications |
Group1 |
Group 2 |
Total |
P value |
| Convulsion
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4 (8%) |
12 (25%) |
16 |
Chi-Square= 5.79
p<0.05 (for convulsion) |
| Oliguria
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8 (16%) |
5 (10.4%) |
13 |
| Hematuria
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3 (6%) |
5 (10.4%) |
8 |
| Respiratory
depression |
2 (4%) |
0 (0%) |
2 |
| Blurred vision
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2 (4%) |
1 (2%) |
3 |
| PPH |
0 (0%) |
2 (4.1%) |
2 |
| No complications |
31 |
26 |
57 |
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Table 4: Neonatal outcome in
Group 1 and Group 2 |
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Group 1 (n=50) |
Group 2 (n=48) |
Total |
P value |
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Apgar
score at five minutes of birth |
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7-10 |
20 (40%) |
23 (47.9%) |
43 |
Chi-Square= 0.62 p>0.05 |
|
3-6 |
16 (32%) |
5 (10.4%) |
21 |
Chi-Square= 6.78 p<0.01 |
|
<3 |
12 (24%) |
20 (41.6%) |
32 |
Chi-Square= 1.77 p>0.05 |
| Still
birth |
2 (4%) |
0 (0%) |
2 |
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| Total
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50 |
48 |
98 |
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Stay
at NICU |
| <24 hours |
4 |
5 |
9 |
Chi-Square= 0.08
p>0.05 |
| >24 hours |
14 |
15 |
29 |
| Total
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18 |
20 |
38 |
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Eclampsia remains a complex
and partially understood disease and its prophylaxis is the area of
greatest controversy. Although magnesium sulphate is a proven anticonvulsant
in eclampsia, its role in prophylaxis is less certain.
The American College of Obstetrician
and Gynecologists recommends the use of magnesium sulphate in every
woman with a diagnosis of preeclampsia during labor and the post partum
period.(4) Hence it is the practice in different institutions to administer
prophylactic magnesium sulphate to all women with preeclampsia during
labor and for 24 hours postpartum.(2,5,6) But many have expressed concern
at the potentially lethal side effects exerted by magnesium sulphate
at the high doses that are to be attained to prevent convulsions.(2)
The four large randomized trials discussed by Sibai BM shows a lower
rate of eclampsia in those assigned to magnesium sulphate (0.6% versus
2.0%). Thus the number of women needed to treat to prevent one case
of eclampsia is 71.(7) Follow up data from Magpie Trial, where 9996
women were randomized in 33 countries to receive either magnesim sulphate,
or placebo, shows a 58% lower risk of eclampsia in the group made to
receive magnesium sulphate. The number of women with preeclampsia who
needed to be treated to prevent one case of ecclampsia was 324 in high
GNI countries but 43 in low GNI countries. Restricting this prophylaxis
for severe preeclampsia would lower the expenditure considerably.(8,9)
We had a much higher incidence of eclampsia in the severely preeclamptic
mothers not receiving magnesium sulphate than the group receiving it
(25% versus 8%). Efficacy of magnesium sulphate to control convulsion
is found to be 68%. Maternal respiratory depression has been a
serious concern.(7,10) Two women receiving the drug had respiratory
depression but it was not significant when analyzed statistically. Although PPH
has been reported to be associated with prophylactic magnesium sulphate
use (11), we had no patient with PPH although 4% in the control group.
Magnesium sulphate did not affect the outcome of labor like admission
delivery intervals and rate of Cesarean section. This conforms with
some of the previous studies.(11,12) While one study reports a high
rate of Cesarean section (68.5%) done mostly due to fetal distress (38.6%)
(13), we had a Cesarean delivery rate of 50% in the group receiving
magnesium sulphate, mostly done for uncontrolled hypertension (42.8%)
and fetal distress (28.5%). But the rate in the control group was similar
with no statistically significant difference. Since magnesium sulphate
crosses the placental barrier, there has been concern about its safety
for the neonates. Some are of the opinion that the high cumulative doses
of magnesium sulphate may be associated with infant mortality.(14)
Even Sibai BM states that prophylactic magnesium sulphate has no significant
benefit in perinatal outcome.(7) The overall neonatal outcome was better
in our study group as regards the Apgar scores and duration of stay
at NICU with only two still births (4%). This is in accordance to some previous
studies.(8,11)
The Magpie Trial showed no
substantitive harmful effects on babies born to mothers on prophylactic
magnesium sulphate in the short term. Follow up study done on the same
subjects has further proved no death or neurosensory disability at the age of 18
months for such babies.(15)
Magnesium sulphate is a fairly
safe and effective prophylactic agent for eclampsia when used during
labor and 24 hours postpartum in women with severe preeclampsia. At
the same time it should be accepted that even when given to women with
the highest risk of eclampsia, it fails to prevent the onset of convulsion
in all of them. Further studies are needed till we find the perfect
antidote to this dreadful obstetric condition.
- Anthony J, Johanson
RB, Duley L. Role of magnesium sulfate in seizure prevention in patients
with eclampsia and preeclampsia. Drug Saf. 1996 Sep;15(3):188-99.
- Hall DR, Odendaal
HJ, Smith M. Is the prophylactic administration of magnesium sulphate
in women with preeclampsia indicated prior to labour? British Journal
of Obstetrics & Gynecology. July 2000;107:903-908.
- Lowe SA, Brown MA,
Dekker GA et al. Guidelines for the management of hypertensive disorders
of pregnancy 2008. Australian and New Zealand Journal of Obstetrics
and Gynecology 2009;49:242-246.
- American College
of Obstetricians and Gynecologists:Management of preeclampsia. Technical
Bulletin 1986;No 91.
- Repke JT, Friedman
SA, Kaplan PW. Prophylaxis of eclamptic seizures: current controversies.
Clin Obstet Gynecol 1992 Jun;35(2):365-374.
- Sibai BM. Diagnosis
and management of gestational hypertension and preeclampsia. Obstetrics
& Gynecology: High-risk pregnancy series: An expert’s view. Jul
2003;102(1):181-192.
- Sibai BM. Magnesium
sulfate prophylaxis in preeclampsia: Lessons learned from recent trials.
Am J Obstet Gynecol. 2004 Jun;190(6):1520-6.
- Altman D, Carroli
G, Duley L et al. Magpie Trial Collaborative Group. Do women with preeclampsia,
and their babies benefit from magnesium sulphate? The Magpie Trial:
a randomized placebo controlled trial. Lancet. 2002 Jun;359(9321):1877-1890.
- Simon J, Gray A,
Duley L Magpie Trial Collaborative Group. Cost-effectiveness of prophylactic
magnesium sulphate for 9996 women with preeclampsia from 33 contries:
economic evaluation of te Magpie Trial. BJOG 2006 Feb;113(2):144-151.
- Rozenberg P. Magnesium
sulphate for the management of preeclampsia. Gynecol Obstet Fertil 2006
Jan;34(1):54-59.
- Whitlin AG, Friedman
SA, Sibai BM. 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 Mar;176(3):623-627.
- Leveno KJ, Alexander
JM, McIntire DD. Does magnesium sulfate given for prevention of eclampsia
affect the outcome of labor? Am J Obstet Gynecol. 1998 Apr;178(4):707-712.
- Hall DR, Odendaal
HJ, Smith M. Is the prophylactic administration of magnesium sulphate
in women with pre-eclampsia indicated prior to labour? BJOG 2000 Jul;107(7):903-908.
- Azaria E, Tsatsaris
V, Goffinet F et al. Magnesium sulfate in obstetrics: current data.
J Gynecol Obstet Biol Reprod (Paris) 2004 Oct;33(6 Pt 1):510-517.
- Magpie Trial Follow
up Study Collaborative Group - The Magpie Trial: a randomized trial comparing
magnesium sulfate with placebo for preeclampsia outcome for children
at 18 months. BJOG 2007 Mar;114(3):289-299.
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