202
Management of Severe
Pre-eclapmsia and Eclampsia
INTRODUCTION
Hypertension is a common problem occurring in
around 12–15% of all pregnancies1. It remains one of
the major causes of maternal mortality2. Because of
the difficulty in deciding who has a problem and
who does not, obstetricians often admit a patient to
hospital for closer observation. This approach can
cause much inconvenience to the patient and her
family. In-patient management may vary between
different hospitals but the cornerstone is hospitali-
zation in order to maintain close monitoring.
The outcome of pre-eclampsia changes depends
on severity. Maternal and perinatal mortality and
morbidity in the hospitalized case with mild pre-
eclampsia are extremely low and approach those of
normotensive pregnancies. In contrast, in the case of
severe pre-eclampsia, maternal and perinatal
mortality is very high. Sibai and colleagues3 reported
that the corrected perinatal mortality rate in severe
pre-eclampsia is 135 in 1000. In this study, the
perinatal survival rate was zero in those cases up to
28 weeks’ gestation, but rose to 100% after 36 weeks’
gestation, especially in cases of pre-eclampsia with
hemolysis, elevated liver enzymes and low platelet
(HELLP) syndrome when the perinatal mortality
ranged from 77 to 600 per thousand and maternal
mortality from 0% to 24%. Based on this experience,
prompt delivery was recommended after stabilizing
maternal condition4,5.
C Sen
Doppler studies on uterine artery and fibronectin
measurements in maternal blood have been
predictive methods for pre-eclampsia with 77% and
90% sensitivity, respectively6,7 . In these high-risk
patients low-dose aspirin can be given as a
prophylaxis, but recent studies have shown that there
is no apparent beneficial effect on clinical outcome8,9.
At the present time there is no effective method that
can prevent the complications of pre-eclampsia, and
clinical management of severe cases is becoming an
important issue.
The most important therapy for severe pre-
eclampsia and eclampsia is delivery of the fetus and
placenta and there is universal agreement that all
such patients should be delivered at or after 32–34
weeks’ gestation and, in cases of severe pre-
eclampsia, delivery has to be taken into account
between 28 and 32 weeks’ gestation, depending on
the situation. At this stage, the neonatal mortality
rate is not very high depending on the ability and
experience of the neonatal intensive care unit 10 .
Timing the delivery in cases of severe pre-eclampsia
at a gestational age of less than 28 weeks is a difficult
decision for the mother and obstetrician to make.
Aggressive management with immediate delivery
will result in extremely high neonatal mortality and
morbidity. In contrast, attempts to prolong pregnancy
may result in fetal demise and high maternal
morbidity and mortality. The perinatal survival rate
 Management of Severe Pre-eclampsia and Eclampsia
is poor when the disease develops before 24 weeks’
gestation (2%); however, after that stage the survival
rate is good (50%)11.
In a study with 252 cases of hypertension in
pregnancy, the maternal mortality rate was 0.4%
(eclamptic case with Cesarean section). Overall
perinatal mortality in those cases with hypertension
in pregnancy was 182/1000 which is 2.5-fold higher
compared to the perinatal mortality at this hospital12.
In those cases of severe pre-eclampsia, the perinatal
mortality was about 300/1000. Most of the cases had
not received any antenatal care or were referred
patients who had received conservative management
with antihypertensive therapy over a long period.
In this study, the perinatal mortality was 116/1000
in those cases after 32 weeks’ gestation and 686/1000
in those of less than 32 weeks’ gestation. The rate of
intrauterine growth retardation (IUGR) in patients
with severe pre-eclampsia was 92.3% for those cases
below 32 weeks’ gestation and 40% in those cases
above 32 weeks’ gestation. The average rate of IUGR
was 54.2% in the severe pre-eclamptic cases. For this
reason maximum attention should be paid to the fetus
(e.g. non-stress test (NST), Doppler assessment). In
addition, there was no beneficial effect of Cesarean
delivery on perinatal mortality in case of pre-
eclampsia and eclampsia.
Maternal mortality in the case of eclampsia is
usually associated with mismanaged or complicated
cases. Maternal morbidity is greater in multigravidae
than in primigravidae. This difference may be due
to a higher incidence of chronic hypertension and
underlying renal disease in multigravidae. The
complication rate is also higher in patients who have
had no antenatal care. The fetus of the eclamptic
woman is particularly at risk from abruptio placentae,
preterm delivery, IUGR and fetal distress during
seizure. In a study from Turkey13, the rate of maternal
mortality in cases of hypertension in pregnancy
varied in the different regions, while the rate of
maternal mortality was about 0.52–1.20% in urban
areas; in the rural areas, where antenatal care is not
satisfactory, the perinatal mortality was 2.90–5.20%.
2691
The clinical course of patients with severe pre-
eclampsia may be associated with progressive
deterioration in maternal and fetal condition. In the
case of severe pre-eclampsia, both the mother and
the fetus are at risk for morbidity and mortality. Some
clinical signs and symptoms, such as hypertension,
proteinuria, edema or other parameters, might
indicate the level of pathophysiology in relation to
the severity of the disease and endothelial cell
damage. With regard to endothelial cell damage and
vascular pathology, the risk of vascular damage for
the mother would appear to increase after the
diastolic blood pressure had reached 110 mmHg,
whereas an increased risk to the baby has been
shown to correlate with a diastolic blood pressure
above 95 mmHg14. There is universal agreement that
all such patients should be delivered at or after 32–
34 weeks’ gestation, or if there is any evidence of
premature rupture of membranes, IUGR,
oligohydramnios or fetal and/or maternal distress
at any gestational age. However, there is
disagreement on the management of patients with
severe pre-eclampsia before 32 weeks’ gestation.
Some authors consider delivery as a definitive
therapy for all patients with severe pre-eclampsia
regardless of gestational age; others recommend
expectant management3,15. In the literature it is not
always possible to compare the studies because their
design differs in definition, clinical decision and
follow-up and studies are retrospective. There is also
no agreement on the classification of hypertension
in pregnancy. ACOG and ISSHP (International Society
for the Study of Hypertension in Pregnancy)
classifications are mostly used, but both are not
clinically well applicable. The outcome of severe pre-
eclamptic cases differs depending on definition and
clinical management. If the pathology is severe
enough in the case of severe pre-eclampsia, the
maternal morbidity and mortality are very high. In
some cases with severe pre-eclampsia where the
blood pressure is high but the other clinical
parameters are not severe, the pathophysiology may
not be severe enough to put the mother at risk of
2692 Textbook of Perinatal Medicine
severe morbidity or mortality. We need to
differentiate therefore between which patient should
have expectant management and induction of labor,
and which criteria we should apply to make a decision
for delivery in the case of expectant manage-ment
with severe pre-eclampsia.
EXPECTANT MANAGEMENT
IN SEVERE PRE-ECLAMPSIA
There is no controversy on the management of the
cases with chronic hypertension, gestational
hypertension and mild pre-eclampsia at any
gestational age. These cases consist of a mild group
and maternal–perinatal mortality and morbidity
(mild pre-eclampsia has high perinatal morbidity) are
not high and patients are delivered at term. In severe
cases, because the maternal–perinatal morbidity and
mortality are very high, delivery should be after 32
weeks’ gestation when fetal lung maturity is
completed. However, there is controversy in the
literature on management of the cases with severe
pre-eclampsia at a gestational age of less than 32
weeks because of high perinatal mortality. While
delivery has long been felt to be the best therapeutic
regimen for the mother with severe pre-eclampsia,
in certain cases remote from term it may not be the
best for the fetus. As methods for monitoring both
maternal and fetal well-being have been improved,
expectant management in an attempt to prolong
gestation is an alternative option.
When the extent of the maternal antenatal
management is compared with the costs of neonatal
intensive care, it is obvious that intensive care for
prolonged periods of time is more complicated and
also therefore more costly. For developing countries
with limited resources available for sophisticated
treatment, expectant management is recommended
providing that the level of care is adequate to detect
any maternal complications early. The expectant
management can be beneficial to the fetus without
exposing the mother to severe risks.
In a study 16 a randomized clinical trial was
conducted in which patients with severe pre-
eclampsia between 26 and 36 weeks’ gestation were
assigned to be treated with either nifedipine or
hydralazine. The authors found better control of
blood pressure and a lower incidence of fetal distress
in the group managed with nifedipine. In addition,
the group managed with nifedipine had a better
perinatal outcome than those receiving hydralazine.
They concluded that nifedipine is a safe and effective
drug in the management of patients with severe pre-
eclampsia remote from term.
Odendaal and colleagues17 described the results
of conservative management in 129 patients with
severe pre-eclampsia before 34 weeks’ gestation. The
patients were managed with bed rest, anti-
hypertensive therapy and frequent evaluation of
maternal and fetal well-being. These pregnancies
were prolonged for an average of 11 days. The
overall perinatal mortality was 326/1000.
MODERATE AND SEVERE PRE-ECLAMPSIA
Some authors suggest that severe pre-eclampsia cases
at a gestational age of between 26 and 32 weeks can
be managed conservatively in a close follow-up at
the hospital, but in the literature there is no clear
definition of which case is suitable for expectant
management.
In order to evaluate and properly manage the
cases with hypertension in pregnancy we should
identify which case is at high risk. In our practice we
classify cases with hypertension in pregnancy as
follows:
1. Chronic hypertension;
2. Gestational hypertension (hypertension in this
pregnancy without proteinuria);
3. Mild pre-eclampsia (hypertension < 10 mmHg
diastolic pressure and proteinuria > 0.5 g/l and
< 5 g/l);
4. Moderate pre-eclampsia (hypertension
= 110 mmHg diastolic pressure and proteinuria
< 5 g/l, no other clinical/laboratory signs for
severity);
5. Severe pre-eclampsia (hypertension = 110 mmHg
and/or proteinuria > 5 g/l, and/or clinical/
laboratory sign for severity such as oliguria,
scotomata, headache, confusion, epigastric pain,
 Management of Severe Pre-eclampsia and Eclampsia
retinal hemorrhage, pulmonary edema, HELLP
syndrome) or a moderate pre-eclampsia which
cannot be controlled by antihypertensive
therapy;
6. Superimposed pre-eclampsia;
7. Eclampsia.
The cases with moderate pre-eclampsia, as
classified above, can be managed with expectant
management. At this stage of the pathophysiology
the blood supply from mother to the placenta and
hence to the fetus can be achieved by increased blood
pressure. The pathophysiology is not generally
systemic and the organ systems of the mother are
not compromised. There is no increased risk for the
mother but fetal morbidity and mortality are very
high. The method of assessment for the fetus at risk
will be discussed later on (NST, Doppler, fetal blood
sampling). Another important point is that the
expectantly managed pregnant woman should be
hospitalized and followed intensively for the
probability of a severe form of pre-eclampsia which
can cause severe maternal morbidity and mortality.
For this purpose the patients are hospitalized and
given special care in the hospital. For the moderate
pre-eclampsia, proteinuria should not be higher than
5 g/l with no other clinical/laboratory sign for
severity. After bed rest in the hospital, the diastolic
blood pressure might be decreased to less than 110
mmHg without any medication. If not, an anti-
hypertensive drug such as nifedipine can be given to
keep the diastolic pressure level between 90 and 100
mmHg. If the patient is treated by antihypertensive
therapy this may cause relatively decreased blood
flow in the uterine artery and fetal hypoxia. Also,
fetal demise should be expected if the blood pressure
is prominently decreased. We should remember that
in both moderate and severe cases, perinatal
morbidity such as IUGR (45.8%) is higher than in
mild cases (10.2%) 12 . The evidence of IUGR and
oligohydramnios is an indication for induction of
labor in the case of moderate pre-eclampsia.
If any of the following signs is becoming evident,
the case should be categorized as severe pre-eclampsia
and labor should be induced: diastolic pressure more
2693
than 110 mmHg in spite of antihypertensive therapy,
increased proteinuria to 5 g/l or more, any clinical/
laboratory sign for severity during follow-up in the
hospital. In that case, delivery should be the
recommended approach to the patient because of high
maternal morbidity and mortality as well as high
perinatal mortality.
The aim of expectant management for cases with
moderate pre-eclampsia is to gain more time for the
fetus to mature. It can be possible to prolong the
pregnancy approximately 7–10 days but usually no
longer. It should be expected that the patient with
expectant management may move to the severe
category at any time. Daily NST and Doppler
assessment should be carried out. Biochemical
parameters for severe pre-eclampsia (uric acid,
platelets, Hb, bilirubin, transaminases, fundoscopic
evaluation) should be checked at least every other
day. Close clinical follow-up and blood pressure
monitoring at least four times a day are essential
clinical work up. These moderate cases should be
managed by a person who has experience of these
cases, preferably at a tertiary center.
FETAL SURVEILLANCE
The NST is a useful test, which has 88% specificity
and 50% sensitivity for fetal well-being 18,19 . The
oxytocin challenge test (OCT) has no extra value
compared to the NST and also can be hazardous.
Doppler study and NST are both more accurate in
IUGR and oligohydram-nios cases. In a study20,21 of
IUGR cases with oligo-hydramnios, 90% of the cases
with abnormal Doppler findings were acidemic. In
cases of oligohydramnios without IUGR with normal
findings, both Doppler and NST were 20% acidemic.
We should remember that in the case of IUGR, the
risk for fetal hypoxemia is very high and delivery is
mandatory. In the case of oligohydramnios there is
high risk for fetal hypoxemia which remains up to
20%. Fetal blood sampling may help to rule out the
risk of fetal hypoxia or acidemia in a tertiary center.
Fetal biophysical profile (FBP) may also help in high-
risk cases but is time consuming. Meanwhile the
combination of NST and amniotic fluid volume
2694 Textbook of Perinatal Medicine
measurement (AFV) is a reliable and time-saving
method with similar sensitivity and specificity rates
as FBP22. In any category of pre-eclampsia, any case
with IUGR and oligohydramnios should be
delivered. In some cases with moderate pre-eclampsia
and borderline IUGR without oligohydramnios at a
gestational age of less than 28 weeks, if NST and
Doppler findings are normal, can be managed
conservatively. Recently, it has been shown23 that
monitoring of the fetal venous circulation represents
a more accurate method of determining the optimum
time of delivery than antenatal cardiotocograph and
also can predict fetal compromise earlier than
antenatal cardiotocography. It should be kept in mind
that another important risk is abruptio placentae and
eclampsia that should be taken into consideration in
moderate pre-eclampsia managed expectantly.
ANTIHYPERTENSIVE THERAPY IN MODERATE/
SEVERE PRE-ECLAMPSIA
In severe pre-eclampsia, a blood pressure more than
180/110 mmHg, mainly a diastolic pressure of more
than 110 mmHg is a risk factor for intracerebral
bleeding, tissue hypoxia and abruptio placentae
which can cause maternal or fetal morbidity and
mortality. In this situation, to control the blood
pressure, antihypertensive medications should be
given to the mother until delivery.
Pre-eclampsia might be better explained and
defined as a platelet/endothelial cell disorder rather
than a primary hypertensive disease. For that reason
using antihypertensive drugs is not the best treatment
for the disease. The clinical manifestations of
moderate or severe pre-eclampsia are consistent with
a systemic disorder in which severe hypertension is
only one aspect of the pathophysiology. Patients
presenting with such multiorgan disease are often
both a diagnostic and a therapeutic challenge. For
that reason treating the mother by antihypertensive
medications should not be the main therapeutic
approach. The control of hypertension may prevent
some complications such as intracerebral hemorrhage
and cardiac failure in which severe proteinuria and
other compromised systemic organ functions are not
evident. The aim of antihypertensive therapy in the
case of moderate pre-eclampsia at less than 32 weeks’
gestation is to gain more time and to reduce the risk
of respiratory distress syndrome. If there is IUGR
and oligohydramnios, the fetus is probably at risk
as well as the mother. For that reason there is no
indication for using antihypertensive therapy and in
that situation the best option is delivery at any
gestational age.
Different types of antihypertensive agents have
been used for the long- or short-term treatment of
hypertension in pregnancy. Methyldopa is one of the
antihypertensive agents whose long-term safety for
both the mother and the fetus have been adequately
assessed. It reduces systemic vascular resistance
without significant physiological changes on heart
or cardiac output, while renal blood flow is
maintained. Plasma half-life and also peak plasma
levels after oral administration are approximately 2
h. However, decrease in arterial pressure is maximal
about 4–8 h after an oral dose of methyldopa. The
usual dose is 1–2 g/day given in four divided doses
although sometimes 4 g/day are needed.
Clonidine is a potent a2 receptor to central
stimulator and has some side-effects such as sedation,
dry mouth and rebound hypertension following an
abrupt discontinuation. The usual oral dose is 0.1–
0.3 mg/day given in two divided doses and up to a
maximum of 1.2 mg/day as needed. Horvath and
co-workers25 studied this drug and concluded that
clonidine was a safe and effective antihypertensive
agent.
Sodium nitroprusside is a potent arterial and
venous dilator, which is used extensively in the
treatment of cases with malignant hypertension in
non-pregnant patients. It has a rapid onset and a
short duration of action. This agent should be used
only in extreme emergencies in pregnancy because
of the potential risks of fetal cyanide poisoning and
metabolic acidosis26.
b-blockers (propanolol, metropolol and atenolol)
have different hemodynamic effects that depend on
their receptor selectivity. The type of action of b-
blockers is competitive inhibition of catecholamines
 Management of Severe Pre-eclampsia and Eclampsia
at b1 (heart) and b2 (peripheral circulation, bronchi
and uterus) adrenoreceptors. Side-effects are
bronchial spasm, hypoglycemia, cold extremities and
a disturbance in lipid metabolism, neonatal
bradycardia, neonatal hyper-glycemia, fetal growth
retardation and neonatal respiratory depression27 .
Because of the concern regarding side-effects such
as fetal growth retardation, the use of this drug
should be limited.
Labetalol is a combined a- and b-adrenoreceptor
blocker. The additional property of a-blockade
induces vasodilatation improving the primary
vasospasm in this disorder. The usual dose is 33 mg
daily up to 2400 mg/day as required. It appears to
be safe like methyldopa for short-term use in the
third trimester, but it has an increased incidence of
fetal growth retardation in the case of long-term
use28.
Diuretics decrease the blood pressure by
decreasing the intravascular volume and cardiac
output. The most commonly used diuretics of the
non-pregnant hypertensives are the thiazide
diuretics. However, the use of diuretics in case of
pre-eclampsia should be restricted to the patients
whose pregnancy is complicated by pulmonary edema
or excessive fluid retention or to certain patients with
renal disease.
Hydralazine has a direct relaxation effect on
arterial smooth muscle and is associated with
stimulation of the sympathetic nervous system
resulting in an increased heart rate and contractility.
Maternal side-effects are headache, flushing,
palpitations, nausea and vomiting. Drug-induced
lupus syndrome is generally observed only after
long-term oral use. Uteroplacental blood flow may
decrease following parenteral administration, which
can cause fetal distress. Hydralazine may accumulate
after continuous intravenous infusion resulting in
hypertension and therefore it should be administered
in small intravenous amounts of 5–10 g at intervals
because the onset of the effect may be delayed for
15–20 min.
Comparative trials between hydralazine,
nifedipine and labetalol have not shown one agent
2695
to be superior in the acute management of severe
hypertension16,28,29. Calcium channel blockers (such
as nifedipine, nicardipine, isradipine, nimodipine and
verapamil) are potent antihypertensive agents that
depress the myogenic tone of precapillary arterioles.
The most frequent side-effects associated with these
drugs are secondary to the acute vasodilatation.
Nicardipine has been studied30 and demonstrated
to reduce maternal blood pressure without increasing
neonatal morbidity. Additionally, Doppler flow
studies of the umbilical artery were not significantly
affected by nicardipine therapy. Long-term therapy
was well tolerated by the mother with no adverse
fetal/neonatal side-effects.
Intravenous isradipine studied by Ingemarsson
and associates 31 was found to normalize blood
pressure 15–30 min after injection. There was no
change in Doppler velocimetry of the umbilical
arteries. Wide-Swensson and co-workers 32
performed a randomized placebo-controlled trial of
a slow-release form of isradipine in women with
gestational hypertension. Again, they demonstrated
the effect of isradipine on decreasing maternal blood
pressure without demonstrating an effect on vascular
flow.
Belfort and colleagues 33 studied the
hemodynamic effects of verapamil administration in
nine women with proteinuric hypertension. These
patients had an intravenous infusion of verapamil,
after plasma volume expansion with dextran-70, until
a 20% reduction in mean arterial pressure was
obtained. They concluded that verapamil is a good
antihypertensive agent to be used in hypertension
in pregnancy but deemed that caution was indicated
when it was used in combination with magnesium
sulfate.
Nifedipine was found to be extremely effective
in the acute treatment of severe hypertension in
pregnancy. In patients treated with daily nifedipine
and serially followed by maternal blood pressure
and fetal Doppler studies, it was demonstrated that
a significant decrease occurred in maternal blood
pressure without any change in resistance index in
the umbilical and uterine arteries or in the fetal aorta.
2696 Textbook of Perinatal Medicine
The Apgar scores and arterial blood gases were not
consistent with fetal compromise. In a retrospective
study, Sibai and colleagues 34 studied the effect of
nifedipine on 200 women between 26 and 36 weeks’
gestation. Nifedipine was associated with
significantly lower blood pressure and good perinatal
outcome.
Many of the calcium channel blocker agents have
been found to inhibit platelet aggregation, both in
vivo and in vitro. Rubin and colleagues35 studied ten
women with proteinuric gestational hypertension
and noted a statistically significant increase in the
mean platelet count which they attributed to
nifedipine. They concluded that nifedipine reversed
thrombocytopenia and controlled blood pressure in
patients with gestational hypertension.
In conclusion, calcium channel blockers such as
nifedipine have been used for many years in pregnant
women with good effect. In many cases, they are
effective and safe for the mother and the fetus when
used carefully and are inexpensive. Additional
benefits may be derived from vasodilator and anti-
aggregational effects. In the acute situation, calcium
channel blockers such as nifedipine can be given
sublingually 10 mg two or three times at 15-min
intervals. Blood pressure decreases slowly to an
appropriate level and then is maintained with 10 mg
three or four times a day at 6–8-h intervals. The onset
of action occurs within 10 min of administration and
the peak action occurs after 30 min, with the blood
pressure control maintained for approximately 4 h.
It should be remembered that the daily maximum
dose should not exceed 120 mg/day because of
maternal side-effects. Mild side-effects and a short
half-life, plus a rapid but not very deep response,
make this drug preferable to others. In moderate
pre-eclampsia there is no need to add any alternative
antihypertensive agent. In this situation the case
should be classified as severe pre-eclampsia and be
delivered after stabilization of the mother.
MATERNAL VOLUME EXPANSION
The clinical consequences of vasodilatation without
volume expansion include precipitous falls in blood
pressure as well as the onset of peripheral ischemia,
most clearly evident as a fall in renal output and the
development of fetal distress 36 . Preloading the
patient prior to vasodilatation is known to prevent
these complications and also facilitates subsequent
vasodilatation.
Fluid therapy in pre-eclampsia has traditionally
been monitored by the use of central venous pressure
(CVP) lines, but CVP readings, while acting as a good
index of overall intravascular volume, do not give
any indication of the left ventricular response to acute
volume expansion. Central monitoring, to be
meaningful, requires right heart catheterization in
order to measure pulmonary capillary wedge
pressure. In practice, these severe patients should
never be exposed to acute plasma volume expansion
of more than 30 ml of fluid.
ECLAMPSIA
Eclampsia is associated with multiple organ
dysfunction. The question of whether or not
eclampsia is a preventable complication is
controversial. Campbell and co-workers37 studied
factors leading to the development of eclampsia in
66 women and concluded that convulsions were not
preventable in 42% of the cases.
The first action should be to control convulsions.
As a first line, 10 mg intravenous diazepam can be
given as a bolus and then 3–4 mg of magnesium
sulfate be administered as a bolus. After convulsions
have been abolished, the magnesium sulfate
perfusion should be maintained at 1–1.5 g/h for at
least 24 h. Arterial blood gas measurements,
magnesium level in the blood and a chest radiograph
should be obtained to ensure adequate maternal
oxygenation and to avoid over-perfusion of
magnesium. Hypoxemia and acidemia should be
corrected. Hydralazine or labetalol can be
intravenously administered, or sublingual/oral
calcium channel blockers can be used to control the
blood pressure. Intensive care of the patient is
necessary. Occasionally it is not possible to control
the convulsions. In that situation the woman should
be cared for in the intensive care unit under the
 Management of Severe Pre-eclampsia and Eclampsia
perfusion of sodium thiopental. The seizures can be
prevented with this therapeutic approach.
In some cases, fetal bradycardia or signs of fetal
distress can be seen during or just after seizures. In
this situation, there is no hurry to perform immediate
Cesarean section. Because of maternal distress, the
placental flow is not in the optimum condition and
temporary fetoplacental insufficiency is present. After
abolishing the seizures, maternal oxygenation and
hemodynamic condition recover. At this stage, any
sign of fetal distress disappears and fetal well-being
returns. Immediate maternal oxygenation and control
of seizures and blood pressure are significant steps
for fetal well-being. Fetal heart rate usually returns
to normal once convulsions cease. If the bradycardia
persists or the uterus is hypertonic, placental
abruption should be suspected. Following
stabilization of maternal conditions, the next step
should be delivery of the fetus. Induction of labor
with oxytocin is often successful. The fetal heart rate
and uterine activity must be closely monitored.
Eclampsia is not an indication for Cesarean section.
Cesarean section solely for this indication should be
avoided. In the cases of seizure or just after
convulsion, it can cause harmful effects on the
maternal system and increase the maternal morbidity
and the heart rate.
MAGNESIUM SULFATE PROPHYLAXIS IN
SEVERE PRE-ECLAMPSIA
Considerable conflict exists regarding the need for
seizure prophylaxis, the optimal anticonvulsant for
this purpose and the type of hypertension in
pregnancy that increases the patient’s risk. The
recommendations from the literature state that the
essential management of pre-eclampsia includes
preventing convulsions, which involves the use of
parenteral magnesium sulfate38. Magnesium sulfate
is the drug of choice in the United States whilst it is
less frequently used in other countries. Instead,
standard anticonvulsants such as phenytoin,
diazepam and phenobarbital are used frequently for
the treatment of seizures. In Turkey, magnesium
sulfate is the most preferred and used anticonvulsant
2697
for the treatment of convulsions and also for the
prophylaxis of convulsions in the case of severe pre-
eclampsia.
Moodley and Moodley40 addressed the necessity
of anticonvulsant therapy in hypertension in
pregnancy. They randomized 228 women with severe
pre-eclampsia to receive magnesium sulfate with
antihypertensive therapy versus antihypertensive
therapy alone. There was no significant difference
in the number of convulsions, birth weight, Apgar
score or maternal complications between these two
groups. In 1993, Friedman and associates 41
performed a randomized clinical trial on the use of
phenytoin versus magnesium sulfate in 105 patients
with severe pre-eclampsia or eclampsia. They found
that patients receiving phenytoin had more rapid
cervical dilatation and a decreased incidence of
postpartum anemia. There were no seizures in either
group after initiation of therapy.
In 1995 the Eclampsia Trial Collaborative Group
published data42 on the anticonvulsant medication
for the treatment of eclampsia and compared the
efficacy of magnesium sulfate, phenytoin and
diazepam in respect to reduction of seizures in
women with eclampsia. They concluded that
magnesium sulfate is a more effective agent than
either of the other two medications in the prevention
of further seizures, as well as being equally safe. The
use of magnesium sulfate for the prevention of
eclamptic seizures is not entirely without risk.
Magnesium toxicity can culminate in cardio-
respiratory arrest if it is not prevented or treated
immediately. In addition, some studies have reported
low Apgar scores, respiratory depression and
hyperflexia in preterm neonates of mothers receiving
magnesium sulfate43.
Recently, Odendaal and Hall44 performed a study
on maternal and perinatal outcomes by using
prophylactic administration of magnesium sulfate to
patients with early severe pre-eclampsia. They
concluded that the prophylactic use of magnesium
sulfate in patients with severe pre-eclampsia,
especially when they are not in labor, is questionable,
and that, although the use of magnesium sulfate did
2698 Textbook of Perinatal Medicine
not cause severe morbidity, it is a potentially harmful
drug that should be reserved for specific indications.
Cases with severe pre-eclampsia or eclampsia that
present with cerebral or visual disturbances, right
quad-rant abdominal pain, severe headache,
unconsciousness, acute exacerbation in blood
pressure or uncontrolled blood pressure should have
prophylatic therapy because of high seizure risk. Also
in the case of severe pre-eclampsia or eclampsia
during labor or first day of the postpartum period,
prophylactic therapy should be initiated. This
prophylactic therapy can be administered as 3–4 g
magnesium sulfate intravenously given as a bolus
with a caution of side-effects and then perfused 1.5
g/h for 24 h. Under these circumstances there is no
evidence or reason for continuing prophylactic
therapy more than 24 h.
INTRAPARTUM AND POSTPARTUM
MANAGEMENT
Pre-eclampsia or eclampsia alone should not be an
indication for Cesarean section. All women with
severe pre-eclampsia should receive anticonvulsant
prophylaxis during labor or postpartum. In our
institute magnesium sulfate is administered by
controlled intravenous infusion with a loading dose
of 3 or 4 g over 20 min, followed by a maintenance
dose of 1.5 g/h. The infusion is continued throughout
labor and delivery, and at least 12 h postpartum. All
patients should be monitored very closely with special
attention given to fluid intake and output. Patients
with severe pre-eclampsia and eclampsia, particularly
uncontrolled, or those remote from term and those
with the HELLP syndrome are at increased risk for
the development of pulmonary edema and acute renal
failure4.
REFERENCES
1. Cunningham FG, Lindheimer MD. Hypertension in
pregnancy. N Engl Med J 1992;326:927–32.
2. Redman CWG. Eclampsia still kills. Br Med J
1988;296:1209–10.
3. Sibai BM, Spinnato JA, Watson DL, et al. Pregnancy
outcome in 303 cases with severe pre-eclampsia. Obstet
Gynecol 1984;64:319–23.
4. Sibai BM, Taslimi MM, el Nazer A, et al. Maternal–
perinatal outcome associated with the syndrome of
hemolysis, elevated liver enzymes, and low platelet in
severe pre-eclampsia. Am J Obstet Gynecol
1986;155:501–4.
5. Lopez-Llera M, Linares GR, Horta JL. Maternal
mortality rates in eclampsia. Am J Obstet Gynecol
1976;124:149–55.
6. Harrington K, Cooper D, Lees C, et al. Doppler
ultrasound of the uterine arteries: the importance of
bilateral notching in the prediction of pre-eclampsia,
placental abruption or delivery of a small-for-
gestational-age baby. Ultrasound Obstet Gynecol
1966;7:182–8.
7. Sen C, Madazli R, Kavuzlu C, et al. The value of
antithrombin-III and fibronectin in hypertensive
disorders of pregnancy. J Perinat Med 1994;22:29–38.
8. CLASP (Collaborate low-dose Aspirin study in
Pregnancy). A randomized trial of low dose aspirin for
the prevention and treatment of pre-eclampsia among
9384 pregnant women. Lancet 1994;343:619–29.
9. Italian study of aspirin in pregnancy. Low-dose aspirin
in prevention and treatment of intrauterine growth
retardation and pregnancy induced hypertension.
Lancet 1993;341:753–4.
10. Pattinson RC, Odendaal HJ, Dutoit R. Conservative
management of severe proteinuric hypertension before
28 weeks’ gestation. S Afr Med J 1988;73:516–19.
11. Sibai BM, Akl S, Fairlie F, et al. A protocol for managing
severe preeclampsia in the second trimester. Am J
Obstet Gynecol 1990;163:733–5.
12. Sen C, Karagozlu F, Ocak V. Clinical management of
hypertension in pregnancy – Gebelik ve
Hipertansiuonda klinik yonetim. J Perinatol (In Turkey)
1993;1:37–44.
13. Erden AC, Yayla M. Maternal–fetal mortality and
morbidity in preeclampsia and eclampsia. J Perinatol (In
Turkey) 1993;1:24–30.
14. Goldby FS, Beilin LJ. Relationship between arterial
pressure and the permeability of arterioles to carbon
particles in acute hypertension. Cardiovasc Res
1972;6:384–8.
15. Odendaal HJ, Pattinson RC, Bam R. Aggressive or
expectant management for patients with severe
preeclampsia between 28–34 weeks’ gestation: a
randomized controlled trial. Obstet Gynecol
1990;76:1070–3.
16. Fenakel K, Fenakel E, Appleman Z, et al. Nifedipine in
the treatment of severe preeclampsia. Obstet Gynecol
1991;77:331–4.
17. Odendaal HJ, Pattinson RC, Dutoit RD. Fetal and
neonatal outcome in patients with severe preeclampsia
before 34 weeks. S Afr Med J 1987;71:555–8.
18. Ocak V, Sen C, Demirkiran F, et al. FHR monitoring
and perinatal mortality in high-risk pregnancies. Eur J
Obstet Gynecol Reprod Biol 1992;44:59–63.
 Management of Severe Pre-eclampsia and Eclampsia
19. Ocak V, Demirkiran F, Sen C, et al. The predictive value
of fetal heart rate monitoring: retrospective analysis of
2165 high-risk pregnancies. Eur J Obstet Gynecol Reprod
Biol 1992;44:53–8.
20. Sen C. Oligohydramnios and its management. Presented
at the XII International Congress – The Fetus as a Patient.
Grado, Italy, May 1996.
21. Sen C, Uludag S, Madazli R, et al. Doppler flow measure-
ments, NST and fetal blood sampling in the prediction
of fetal acidaemia. Prenat Neonat Med 1996;1(Suppl 1):9.
22. Ocak V, Sen C, Madazli R. Is fetal biophysical profile
with all parameters needed? Matern Fetal Invest
1994;4:37–41.
23. Hecker K, Hackeloer BJ. Cardiotocogram compared to
Doppler investigation of the fetal circulation in the
premature growth-retarded fetus: longitudinal
observations. Ultrasound Obstet Gynecol 1997;9:152–61.
24. Cockburn J, Moar VA, Ounsted NM, et al. Final report
of the study on hypertension during pregnancy: the
effects of specific treatment on the growth and
development of the children. Lancet 1982;1:647–9.
25. Horvath JS, Phippard A, Korda A, et al. Clonidine-
hydrochloride: a safe and effective antihypertensive
agent in pregnancy. Obstet Gynecol 1985;66:634–8.
26. Naulty JN, Cefalo RJ, Lewis PE. Fetal toxicity of
nitroprusside in the pregnant ewe. Am J Obstet Gynecol
1981;139:708–11.
27. Van Zwieten PA, Timmermans PB. MVM: differential
phar-macological properties of beta adrenoreceptor
blocking drugs. J Cardiovasc Pharmacol
1983;5(Suppl):55–7.
28. Blouin PF, Breart GL, Maillard F, et al. Comparison of
antihypertensive efficacy and perinatal safety of
labetalol and methyldopa in the treatment of
hypertension in pregnancy: a randomised controlled
trial. Br J Obstet Gynaecol 1988;95:868–76.
29. Mabie WC, Gonzales AR, Sibai BM, et al. A comparative
trial of labetalol and hydralazine in the acute
management of severe hypertension complicating
pregnancy. Obstet Gynecol 1987;70:328–33.
30. Carbonne B, Jannet D, Touboul C, et al. Nicardipine
treatment of hypertension during pregnancy. Obstet
Gynecol 1993;81:908–14.
31. Ingermarsson I, Wide-Swensson D, Andersson KR, et
al. Maternal and fetal cardiovascular changes after
intravenous injection of isradipine to pregnant women.
Drugs 1990;40:58–9.
32. Wide-Swensson DH, Ingermarsson I, Lunell NO, et al.
Calcium channel blockade (isradipine) in the treatment
2699
of hypertension in pregnancy: a randomized placebo-
controlled study. Am J Obstet Gynecol 1995;173:872–8.
33. Belfort MA, Anthony J, Buccimazza A, et al.
Hemodynamic changes associated with intravenous
infusion of calcium antagonist verapamil in the
treatment of severe gestational proteinuric
hypertension. Obstet Gynecol 1990;75:970–4.
34. Sibai BM, Barton JR, Akl S, et al. A randomized
prospective comparison of nifedipine and bed rest
versus bed rest alone in the management of
preeclampsia remote from term. Am J Obstet Gynecol
1992;167:879–84.
35. Rubin PC, Butters L, McCabe R. Nifedipine and platelets
in preeclampsia. Am J Hypertens 1988;1:175–7.
36. Belfort MA, Anthony J, Kirshon B. respiratory function
in severe gestational proteinuric hypertension: the
effects of rapid volume expansion and subsequent
vasodilatation with verapamil. Br J Obstet Gynaecol
1991;98:964–72.
37. Campbell DM, Templeton AA. Is eclampsia preventable.
In Bonnar J, MacGillivary I, Symonds EM, eds.
Pregnancy Hypertension. Baltimore: University Park
Press, 1980:483–9.
38. American College of Obstetricians and Gynecologists.
Management of Preeclampsia. Technical Bulletin 91.
Washington DC: American College of Obstetricians and
Gynecologists, 1986.
39. Madazli R, Sen C, Ocak V. Clinical management of
eclampsia (Eklampside klinik yonetim). J Perinatol (In
Turkey) 1993;1:45–9.
40. Moodley J, Moodley VV. Prophylactic anticonvulsant
therapy in hypertensive crises of pregnancy – the need
for a large, randomized trial. Hypertens Preg
1994;13:245–52.
41. Friedman SA, Lim KH, Baker CA, et al. Phenytoin
versus magnesium sulphate in preeclampsia: a pilot
study. Am J Obstet Perinatol 1993;10:233–8.
42. Eclampsia Trial Collaborative Group. Which
anticonvulsant for women with eclampsia? Evidence
from the Collaborative Eclampsia Trial. Lancet
1995;345:1455–63.
43. McGuiness GA, Weinstein MM, Cruikshank DP, et al.
Effects of magnesium sulphate treatment on perinatal
clacium metabolism. II. Neonatal responses. Obstet
Gynecol 1980;56:595–600.
44. Odendaal HJ, Hall DR. Is magnesium sulphate
prophylaxis really necessary in patients with severe
preeclampsia? J Matern Fetal Invest 1996;6:14–18.