J Ayub Med Coll Abbottabad;16(2)
MAGNESIUM SULPHATE IN THE PROPHYLAXIS AND TREATMENT OF ECLAMPSIA
Shehla Noor*, Mussarat Halimi, Nasreen Ruby Faiz, Fouzia Gull, Nasreen Akbar
Department
of Gynaecology, *
Background: Magnesium
Sulphate is considered to be the agent of choice for the control of eclamptic
seizures in pregnant women. Our objectives were to determine frequency of
eclampsia and pre-eclampsia in our unit and to determine the effect of initial
loading dose of magnesium sulphate on maternal and fetal outcome. Methods: This study was carried out in
Department of Gynaecology at
INTRODUCTION
Eclampsia and pre-eclampsia
are important causes of morbidity and mortality during pregnancy childbirth and
puerperium.1 The prevention
of seizure activity in pre-eclampsia and recurrent seizures in eclampsia is an
essential aspect of management.2 A number of different
anticonvulsants are used to control eclamptic fits and to prevent future
seizures.3 In North America, parenteral
magnesium sulphate is the drug of choice for the prevention and treatment of
eclamptic convulsions.4 Magnesium sulphate appears to act as a
cerebral vasodilator (particularly on the small diameter vessels) in patients
with pre eclampsia. With its potential to relieve cerebral ischemia this
vasodilatation may help explain why magnesium sulphate has anti seizure
activity in pre-eclampsia.5 Its dosing schedules and effectiveness
however is empiric, because no randomized trials have demonstrated whether it
works and what is the therapeutic level that might prevent seizure.6 After
the report of collaborative eclampsia trial role of magnesium sulphate for the
control of seizures in eclampsia has been firmly established. In lancet it was
reported six years ago that since magnesium sulphate is cheap and easy to
produce its ready availability should be a priority for all those concerned
with maternal health and the essential drug list of World Health Organization,
and other bodies need to be amended accordingly”.7 But still women
in developing countries are being treated with diazepam and phenytoin, main
problem being the continuous supply of drug. The question whether magnesium
sulphate reduces the risk of eclampsia in women with pre-eclampsia and its
benefits was at last answered by MAGPIE TRIAL conducted by Royal college of Gynaecology, which concludes that Magnesium sulphate
reduces the risk of eclampsia, and it is likely that it also reduces the risk
of maternal death.8 Magnesium sulphate is not a benign drug it is
associated with complications and although most studies have shown that it does
not increase the duration of labour ,maternal blood
loss or caesarean delivery rate, it does change intrapartum
and postpartum care and does affect many maternal and fetal parameter.9 The
aim of this study was to determine the frequency of eclampsia and pre-eclampsia
and to evaluate the maternal and fetal outcome of patients with pre-eclampsia
and eclampsia treated with initial loading dose of magnesium sulphate.
MATERIAL AND METHODS
Hospital history sheets of
all those patients who received magnesium Sulphate from January 2000 to
December 2000 were reviewed and scrutinized. Descriptive statistics were
obtained after chart analysis and review of all notes. Patient who did not
receive Magnesium sulphate were excluded. Frequency of eclampsia was calculated
out of total number of deliveries in one year in that unit.
Magnesium
sulphate was given by intramuscular regimen as described by Pritchard10
and colleagues i.e. loading dose of 4 gm intravenously as 20% solution over
10-15 minutes followed by 5gm into each buttock intramuscularly. As the main
problem with magnesium sulphate was its availability, therefore the dose of
magnesium sulphate was modified. Only loading dose was given, and 5 gm
intramuscular was repeated only if either signs of impending eclampsia
developed or convulsions occurred. Patient was monitored clinically with
respiratory rate (>16/ minutes), urine output (>25ml/hour) and patellar
reflex. Hypertension was controlled with methyldopa and nifedipine.
Induction was started in all cases of eclampsia and severe pre-eclampsia
provided they were not already in labour,
irrespective of gestational age. Maternal outcome was measured regarding
recurrence of convulsions, mode of delivery, any complications during labor ,
delivery and puerperium who were admitted before
delivery of baby, development of complications such as pulmonary edema, cardiac
arrest, respiratory depression, pneumonia, renal failure, disseminated
intravascular coagulation, cerebrovascular accident,
liver failure and maternal death.
Fetal outcome was
measured in terms of perinatal morbidity (Apgar score
<7 at 5 minutes interval, intubations at the time of delivery, nursery
admissions) and mortality.
RESULTS
There were 6693 obstetric
admission from January to December 2000. Total deliveries were 3342. This included 307(4.58%) cases of
hypertension associated with pregnancy, the distribution of whom is given in
table-1.
Total patients
treated with Magnesium sulphate were 133 that included 53 (39.8%) cases of
eclampsia and 80 (60.15%) cases of pre-eclampsia.
Eclampsia and
pre-eclampsia was found to be common in the reproductive age rather than at the
extremes of age as shown in table 2. Eclampsia was common in first pregnancy
i.e. (54.7%) but pre-eclampsia was found to be frequent among grand multigravidae (40%) and multigravidae
(35%) as shown in table 2.
40 patients with
eclampsia were admitted as antenatal cases and 13 as postnatal eclampsia, while
76 cases of pre-eclampsia were antenatal, and 4 were postnatal. Only 9(16.98%) patients
of eclampsia were of more than 37 weeks gestation while 46 (57.5%) patients of
pre-eclampsia were of more than 37 weeks gestation. Majority of patients were
admitted with sever hypertension as shown in table 3(A).
6 patients of
eclampsia had no protienuria. Two patients who were
labeled as cases of pregnancy induced hypertension with mild hypertension of
160/100mmHg respectively and no protienuria,
developed fits in the hospital. One during labour and
another soon after delivery. Both were administered diazepam during the acute
attack and then loading dose of magnesium sulphate.
24 (45.20%)
patients of eclampsia were induced with prostaglandin vaginal pessary while 40(50%) of patients of pre-eclampsia were
already in labour, and labour
was only augmented. 11(13.75%) patients of pre-eclampsia underwent caesarean
section. These were performed purely for obstetrical reasons., 5 patients had
failure to progress, 4 for obstructed labour and 1
each for neglected transverse lie and brow presentation. All these case were
referred from periphery in advanced labour. 24
(45.2%) of eclampsia and 52(65%) of pre eclampsia had normal vaginal deliveries
while 20 (15%) had instrumental deliveries as shown in table 4(b).
6 patients with pre eclampsia and gestational age less than 34 weeks ,who were administered loading dose of magnesium sulphate and anti hypertensive drugs were discharged on conservative treatment after their all clinical and laboratory parameters were improved. One patient with sever preeclampsia left against medical advise.
Table-1: Frequency out of 6693 obstetric admissions
|
|
No. |
% (n=6693) |
Ratio (n=3342) |
|
Eclampsia |
131 |
1.95% |
1 in 25.5 deliveries |
|
Pre-Eclapsia |
97 |
1.44% |
1 in 34.5 deliveries |
|
Pregnancy Induced
Hypertension |
52 |
0.77% |
1 in 64.2 deliveries |
|
Essential Hypertension |
27 |
0.4% |
1 in 123.77 deliveries |
|
Total |
307 |
4.5% |
3342 deliveries |
Table-2: Patient Characteristics
|
|
Eclampsia |
Preeclampsia |
|
A) Age |
||
|
Teenage |
04(7.5%) |
01(1.25%) |
|
20 – 30 |
34(64%) |
43(53.75%) |
|
31 – 40 |
15(28.3%) |
34(42.5%) |
|
Above |
NIL |
02(2.5%) |
B)Parity
|
||
|
Primegravida |
29(54.7%) |
20(25%) |
|
Multigravida |
12(22.6%) |
28(35%) |
|
Grandmulti-gravida |
12(22.6%) |
32(40%) |
|
Total |
53 |
80 |
C) Gestational
Age
|
||
|
<30 |
08 |
07 |
|
30 -34 |
08 |
08 |
|
34-37 |
15 |
15 |
|
<37 |
31(58.49%) |
30(37.50%) |
|
>37 |
09(16.98%) |
46(57.50%) |
|
Postnatal |
13(24.50%) |
04(5%) |
Table-3: Level of Blood Pressure and Albuminuria at Admission
|
|
Eclampsia |
Preeclampsia |
|
A)Hypertension |
||
|
Mild |
18(33.90%) |
14(17.5%) |
|
Severe |
35(66%) |
66(82.5%) |
B)Protienuria
|
||
|
0 |
06 |
NIL |
|
+1 |
13 |
17 |
|
+2 |
09 |
28 |
|
+3 |
12 |
24 |
|
+4 |
13 |
11 |
|
TOTAL |
53 |
80 |
Table-4: Pregnancy & Labour Outcome
|
|
Eclampsia |
Preeclampsia |
Total |
|
A)
Induction |
|||
|
Prostaglandin |
24(45.20) |
15(18.75%) |
39 |
|
ARM+Oxytocin |
05(9.40%) |
09(11.25%) |
14 |
|
Augm-ented |
11(20.75%) |
40(50%) |
51 |
|
Conservative
Treatment=6(Went Home) |
|||
|
Lama =1 |
|||
B)Mode Of Delivery
|
|||
|
NVD |
24(45.20%) |
52(65%) |
76 |
|
Forceps |
09(16.98%) |
03(3.75%) |
2O |
|
Vacuum |
05(9.40) |
03(3.75%) |
|
|
Cesarean |
NIL |
11(13.75%) |
|
In 22(41.5%) and 57(71.2%) cases of eclampsia and preeclampsia. babies were born alive, while 2(3.77%) babies of eclampsia and 8(10%) babies of pre-eclampsia needed nursery admissions. Perinatal mortality was 19(35.8%) in eclampsia and 16(20%) in pre-eclampsia.
Table-5: Perinatal outcome
|
|
Eclampsia |
Preeclampsia |
|
Alive |
24(41.50%) |
57(71.20%) |
|
Fresh Stillbith |
15(28.30%) |
10(12.50%) |
|
Macerated Stillbirth |
01(1.80%) |
02(2.50%) |
|
Neonatal Death |
03(5.60%) |
04(05%) |
|
Perinatal Mortality Rate |
19(35.80%) 358/1000 |
16(20%)200/1000 |
|
Nursery Admission |
02(3.77%) |
08(10%) |
Total 9 patients
died. 8 were of eclampsia and 1 was of pre-eclampsia.One
patient of pre-eclampsia who was admitted with twin pregnancy of 30 weeks
gestation and APH developed postpartum hemorrhage and acute renal failure. She
was transfused fresh frozen plasma and haemodialysed
twice. She recovered completely. Another patient of pre –eclampsia developed
pulmonary edema soon after delivery. She was treated and recovered.
One patient of preeclampsia who had normal vaginal delivery became
unconscious after delivery. She did not have any kind of fits. She was shifted
to I.C.U put on ventilator but expired after 11 hours of delivery probably due
to C.V.A.
Total 8 patients
of eclampsia died. 3 were admitted as postnatal eclampsia (2 were four days
postnatal while one was one day postnatal) All had history of multiple fits and
were deeply unconscious. 3patients who were antenatal were induced. One was
admitted with a full blown HELLP syndrome while 2 were admitted with sever
pulmonary edema. Although all possible emergency measures were taken but died
despite intensive care. 2 patients of eclampsia died undelivered. All these
patients were admitted with history of multiple fits in a very serious
condition and were referred from periphery.
DISCUSSION
This study was a descriptive
study to find about the maternal and fetal outcomes that were treated with
magnesium sulphate. Eclampsia and pre-eclampsia are important causes of
morbidity and mortality during childbirth, and puerperium.1
Eclampsia accounts for approximately 50,000 maternal deaths worldwide annually.11
In Europe and other developed countries eclampsia complicates about 1 in 2000
deliveries while in developing countries estimates vary widely from 1 in 100 to
1 in 1700.3 Thus eclampsia is now largely regarded as disease of developing
countries. And it is one of the leading causes of maternal mortality after
hemorrhage and sepsis. In our study frequency was 1 in 34.4 deliveries of
pre-eclampsia and 1 in 25.5 deliveries of eclampsia. Only two patients of
pre-eclampsia were booked. The high frequency of these conditions reflects the
lack of antenatal care and lack of functioning health care system at primary
and secondary levels. It is also because ours is the only easily accessible
main referral centre for whole of the province. Two patients with pregnancy
induced hypertension without protienuria developed
convulsions in the hospital. Thus on one hand lack of antenatal care may be one
of the predisposing factor for such a high frequency of eclampsia but on the
other hand it may not be easy to predict seizures in cases of pregnancy induced
hypertension. Study by Katz et al questions the traditions that eclampsia
evolves in a fairly linear manner from mild preeclampsia
to sever preeclampsia to seizures. It also question
the assumption that seizures are predictable.9 Mattar
and Sibai conclude that women with mild hypertension
or mild preeclampsia either before labour or intrapartum continuous
evaluation of maternal symptoms and educations of patients and nurses regarding
reporting of these symptoms and the need for immediate medical response to any
of these symptoms are extremely important.12 Most patients with
pregnancy induced hypertension do not progress to seizures.13
In this study six
patients of eclampsia had no protienuria, thus
hypertension and protienuria are neither the only nor
necessarily the most important signs of pre-eclampsia. Douglas and Redman had
noted that protienuria was the only premonitory sign
in 10% of cases and that one third of women had only mild hypertension before
the onset of convulsion.14 Renal function tests, thrombocytopenia,
and abnormal plasma concentration of liver enzymes gives important information
about the extent to which the maternal system is affected.14 Because
of lack of hospital resources and trained laboratory staff in evening and night
these biochemical markers were often not available in the evening and night
time for patients admitted as emergency cases. According to Douglas et al
confirmatory signs should be sought assiduously in the first 48 hours after a
fit even if there are no features of preeclampsia previously.
Thus convulsions may be unheralded by warning sign and symptoms.
A major problem
for preventing and treating eclampsia is that the pathogenesis of this
condition is not known.7 As pre-eclampsia had no preventive
strategy, its management relies on early detection, control of its
manifestation, such as hypertension and ultimately on the delivery of the fetus
and placenta.15
In this study
vaginal delivery was the preferred mode of delivery. Caesarean sections which were
performed in case of pre-eclampsia were mainly done for obstetrical
indications. Thus this study also showed that magnesium sulphate does not
increase the duration of labour, maternal blood loss
or caesarean delivery rate. Perinatal mortality was very high in eclampsia
i.e19 (35.8%) as compared to pre eclampsia i.e. 16(20%). Main cause of this
high perinatal mortality was prematurity and antepartum hemorrhage. Comparatively perinatal mortality
was low, considering the gestational ages. This may be attributed to the affect
of magnesium sulphate on very low birth weight babies. Schendel
et al reported that a reduced risk for cerebral palsy and possibly mental
retardation, among very low birth weight children is associated with prenatal
magnesium sulphate exposure.16 Nelson and Grether
also revealed an 80% reduction in the risk for cerebral palsy associated with intrapartum magnesium sulphate exposure that appeared to be
independent of a variety of perinatal conditions including pre-eclampsia and
number of known risk factors for cerebral palsy.17
Anticonvulsants
are given to women with severe pre-eclampsia with the aim of preventing the
first fit although whether this does more good than harm is unclear.7 Anticonvulsants
are used to prevent recurrence of seizures in patients with eclampsia as well
as in fulminating pre-eclampsia for prophylaxis against seizures.1 There
is now compelling evidence in favor of magnesium sulphate, rather than diazepam
or phenytoin for the treatment of eclampsia.7 Results from the
MAGPIE8 trial demonstrate clearly that magnesium sulphate is
effective in considerably reducing the risk of eclampsia for women with preeclampsia. But still in developing countries such as
ours, diazepam is being used as an
anticonvulsant. The main problem is the free availability of the drug. In our
study patient did not develop convulsions after only the loading dose was
given. In only 2 patients who developed fits dose had to be repeated. Thus the
dose of magnesium sulphate and duration of therapy should be further evaluated
according to the individual and geographical differences, as it is quite
plausible that higher dose will increase the hazards (such as respiratory
arrest without any increase in the benefits associated with the use of
magnesium sulphate..18 Sibai had reported
that approximately 10% to 15% of women with eclampsia will have a second
convulsion after receiving the loading dose of magnesium sulphate. Pritchard et
al reported that 12% who had eclampsia treated before delivery again suffered
convulsions shortly after an initial injection of the loading dose.10
8 patients of
eclampsia and 1 patient of pre eclampsia died, who developed sudden unconciouness. All patients of eclampsia had multiple fits
and were brought to the hospital in very late stage. studies
from
Our study raises
question regarding the routine prophylaxis of magnesium sulphate in
pre-eclampsia and dosage and duration of magnesium sulphate in eclampsia.
Magnesium sulphate is the
drug of choice in eclampsia. Initial loading dose of magnesium sulphate is
effective in prevention and treatment of Eclampsia. As it is cheaper and easy
to administer, and subsequent nursing is easier, it may be appropriate for use
at primary health level so as to reduce maternal morbidity and mortality. As
eclampsia is considered to be a disease of developing countries, prospective
studies are needed regarding dosage and duration of magnesium sulphate therapy.
REFERENCES
1.
Chien PF,
2.
Anthony J, Johanson
RB, Duley L. Role of magnesium sulphate in seizure
prevention in patients with eclampsia and pre eclampsia. Drug saf 1996;15(3):188-99.
3.
Duley L,
Henderson-Smart D. Magnesium sulphate versus diazepam for eclampsia (Cochrane
review). In the Cochrane library, issue 3, 2003
4.
Sibai BM. Magnesium
sulphate is the ideal anticonvulsant in pre eclampsia-eclampsia. Am J Obst Gynecol 1990;162:1141-5.
5.
6.
Burrows RF, Burrows EA. The feasibility of a
control population for a randomized control trial of seizure prophylaxis in the
hypertensive disorders of pregnancy. Am J Obst Gynecol 1995;173:929-35.
7.
Duley L. Which
anticonvulsant for women with eclampsia? Evidence from the collaborative eclampsia
trial. The Lancet. 1995; 345:1455-63.
8.
Duley L. Do women with
pre-eclampsia and their babies benefit from Magnesium sulphate? The MagPie Trial: a randomized placebo-controlled trial. Lancet
2002;359:(9321):1877-90
9.
Katz VL, Farmer R, Kuller
JA. Pre eclampsia into eclampsia. Towards a new paradigm. Am J Obst Gynecol 2000;182:1389-96.
10.
Pritchard JA, Cunnigham
FG, Pritchard SA. Parkland Memorial Hospital Protocol for treatment of Eclampsia.Evaluation of 245 cases. Am J Obst
Gynecol 1984;148:951-63.
11.
Fugate SR, Chow GE. Eclampsia. Retracted from
e-Medicine.
12.
Mattar F, Sibai BM. Risk factors for maternal morbidity. Am J Obst Gynecol 2000; 182:307-12.
13.
14.
15.
Steer PJ. The definition of pre eclampsia.
Commentary. Br J Obstet Gynecol
1999;106:753-5.
16.
17.
Nelson Kb, Grether JK.
Can Magnesium sulphate reduce the risk of cerebral palsy in very Low birth
weight infants? Pediatrics 1995;95:263-9.
18.
Duley L. Magnesium
sulphate regimen for women with eclampsia. Messages from the collaborative
Eclampsia trial. Br J Obstet Gynecol
1996;103:103-5.
______________________________________________________________________________
Address For Correspondence
Dr Shehla Noor, Assistant
Professor, Department of Gynaecology,