Eclampsia: a global problem
Eclampsia: a global problem |
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Oshiomeghe K. Ogah, Senior Registrar; Munir-deen A. Ijaiya, Consultant
Obstetrician & Gynaecologist; Peter A. Aboyeji, Consultant Obstetrician &
Gynaecologist; Samuel A. Esuga, Senior Registrar
Department of obstetrics and gynaecology,
University of Ilorin Teaching Hospital, Maternity Hospital Wing, PMB. 1339,
Ilorin, Nigeria.
Key words: Eclampsia, global, obstetric problem,
management
Introduction
Eclampsia has been identified as a clinical condition since the times of
Hippocrates1. But it was not till the 17th century that the convulsions in
pregnancy were distinguished from tonic clonic fits in the non-pregnant state1.
The term Eclampsia appeared in a treatise on gynaecology written by Varandaeus
in 1619 and clonic spasms in association with pregnancy were described by Dew in
16942. It is a life threatening disease3. Globally it remains one of the leading
causes of maternal morbidity and mortality with higher incidence in developing
than developed countries due to inadequate and poor utilization of maternal
health care facilities3,4. Therefore it is a public health issue. Unfortunately,
there has been little progress in preventing the disorder compared to advances
made in eliminating other major obstetric complications5.
Definition
The International Society for the Study of Hypertension in Pregnancy (ISSHP)
defines eclampsia as the occurrence of generalized convulsion(s) associated with
signs of pre-eclampsia during pregnancy, labour or within 7 days of delivery and
not caused by epilepsy or other convulsive disorders6. It is termed atypical
eclampsia when convulsions occur after seven days of delivery or in the absence
of hypertension7.
Incidence
The incidence and maternal mortality rate associated with eclampsia varies from
locality to locality depending on the prevailing level of maternity care. The
incidence of eclampsia is high in developing countries e.g. Accra, Ghana 13.0
per 1,000 deliveries8; Lagos, Nigeria 16.8 per 1000 deliveries9; while a low
incidence is recorded in developed countries e.g. 4.9 per 10,000 deliveries in
the United Kingdom10. The maternal death rate for eclampsia for some developing
countries may be more than 25% while it is between 1.8% and 7.2% for developed
countries10,11,12.
Pathophysiology
Eclampsia was once thought to be one of the pregnancy toxaemias caused by a
circulating toxin that acted on nerve centre13. In 1916, Zweifel first termed
“toxaemia” the disease of theories, as with pre-eclampsia the exact aetiology of
eclampsia is not well understood14. There is a growing body of evidence
attributing eclamptic seizures to cerebral platelet thrombi; hypoxia due to
localized vasoconstriction; cerebral oedema, ischaemia and petechial
haemorrhages14. There is also a mistaken tendency to equate eclampsia with
hypertensive encephalopathy, but features of hypertensive encephalopathy
(retinal haemorrhages, exudates and papilloedema) are uncommon in eclampsia,
where fundoscopic changes are minimal15.
Usually eclampsia follows poorly controlled pre-eclampsia5, however, it is
difficult to predict which pre-eclamptic woman may go on to convulse and there
is poor correlation between the degree of hypertension present in pre-eclampsia
and occurrence of seizure7. However, the underlying pre-eclampsia is usually
severe, although it can occur in patients with only mild hypertension7.
Clinical features
People at risk of eclampsia include primigravida, teenagers, mothers older than
40 years, negro race, multiple pregnancies, molar pregnancy, women with a
history of diabetes, hypertension or renal disease and those that did not
receive antenatal care3,10.
In most cases, the initial presentation of eclamptic patients is similar to the
patient with severe pre-eclampsia with subsequent development of symptoms and
signs of impending eclampsia which include: severe frontal headache; epigastric
pain; tightening of the chest; nausea/vomiting; visual blurring; hyper-reflexia/sustained
clonus; severe uncontrollable hypertension; oliguria and significant
proteinuria7.
Eclamptic seizures itself are typically grand-mal tonic-clonic convulsions
usually not preceded by an aura and patient may have one or multiple seizures5.
Unconsciousness lasts for a variable period of time. The patient hyperventilates
after the seizure to compensate for the respiratory and lactic acidosis that
develops during apneic phase16. Eclampsia becomes much more frequent as term
approaches. About 50% of eclamptic seizures occur before delivery, 25% during
labour and 25% within 48 hours post-partum10.
Other significant morbidity relates to eclampsia being just one manifestation of
a multisystemic disorder, usually with severe hypertension which may result in
liver dysfunction, HELLP syndrome, disseminated intravascular coagulopathy (DIC),
cerebrovascular accident, haemorrhage, acute renal failure and adult respiratory
distress syndrome (ARDS)7. In addition, there are significant perinatal risks
such as abruptio placenta, foetal distress/demise, perinatal asphyxia and
neonatal death. There is also a background risk of premature delivery and its
attendant problems in pre-term antepartum eclamptics17.
Differential diagnosis
Other conditions that can cause convulsions and coma should be taken into
consideration. These include: epilepsy; hypertensive encephalopathy;
intracranial haemorrhage and thrombosis; meningitis and encephalitis; uraemic
encephalopathy; cerebral tumours and rupture of a cerebral aneurysm17.
Investigation
The diagnosis of eclampsia is clinical and additional diagnostic evaluation is
not always necessary in cases where typical pre-eclampsia precedes the seizure.
Investigations performed should include a haemoglobin level, total white blood
cell count and differential, platelet count, urea, electrolyte status,
creatinine and uric acid level, a coagulation screen, 24 hours total urinary
protein and liver function tests. Cardiotocogram for foetal monitoring when the
fetus is alive7. These tests are done to detect presence of complications and
possible prognosis. When the presentation is not classical and facilities are
available, imaging studies such as brain-computed tomography, magnetic resonance
imaging can be helpful in identifying complications or other seizure
aetiologies18.
Treatment
Eclampsia should be managed in a specialized, well-equipped centre by a combined
team of an obstetrician, obstetric anaesthetist, neonatologist, haematologist
and intensive care nurse with adequate expertise and experience in management of
eclamptic patients17.
The principles of management of Eclampsia include:
1. Control of convulsion
2. Control of hypertension
3. Prompt delivery, if undelivered
The treatment of eclampsia consists of simultaneous: Prompt and effective
resuscitatory care
This involves maintenance of a patent airway preferably with an oropharyngeal
airway. Left lateral positioning to limit aspiration and help maintain airway.
Ensure adequate circulation preferably with central venous pressure monitoring
to prevent fluid overload as eclampsia is associated with intravascular space
contraction. Ringer’s lactate is the intravenous fluid of choice7. Close
monitoring of urine output due to potential risk of acute renal failure and
continuous oxygen administration. Eclamptics require a meticulous surveillance
as the cardiovascular system is extremely labile; as such continuous monitoring
of blood pressure, pulse rate and electrocardiogram as they are prone to
ventricular arrhythmias. Close monitoring of foetal parameters is also
necessary.
Control of convulsions
Eclampsia is best managed in a quiet, darkened environment as loud noise and
bright lights can trigger eclamptic convulsions19. The convulsion is best
controlled with magnesium sulphate, diazepam, chlormethiazole or clonazepam.
Magnesium Sulphate
Magnesium sulphate is the anticonvulsant drug of choice in eclamptics and
popularized by Pritchard et al7. The MgS04 regimens used in Eclampsia include
Pritchard protocol7 in which a loading dose of 4grams over 3-5 minutes is given
intravenously with 5grams given intramuscularly into each buttock, followed by a
maintenance dose of 5grams 4 hourly given intramuscularly. Zuspan et al7
describes giving a loading dose of 4grams over 5-10 minutes intravenously and a
maintenance dose of 1-2grams hourly given intravenously. Sibai7 in South Africa
describes a less cumbersome regimen in which 6grams is given intravenously over
20 minutes as a loading dose and 2grams hourly also intravenously as a
maintenance dose.
Before administration of each dose, it is essential that: urine output is above
30ml/hour, deep tendon reflexes are intact and respiratory rate is above 12
cycles per min.
The above parameters are used in monitoring magnesium sulphate therapy, also the
serum magnesium is measured approximately 4 hours after commencing therapy and
the level kept within 4-8mg/dl therapeutic range. However, it should be measured
hourly if there is evidence of decreased urine output. The maintenance dose of
magnesium sulphate is decreased to 1g/hour if the serum magnesium is >10mg/dl or
patellar reflexes become depressed and increased to 3g/hour if urine output is
brisk or serum magnesium level is falling and/or <4mg/dl. Seizures can occur
while receiving magnesium sulphate. If it occurs within 20 minutes after loading
dose, the convulsion is usually short and no treatment is indicated, however if
the seizure occurs more than 20 minutes after loading dose, an additional 2-4g
of magnesium sulphate may be given19.
Clinical features of magnesium toxicity include: loss of patellar reflex, renal
failure, flushing, somnolence, slurred speech, muscular paralysis, respiratory
difficulty and cardiac arrest17. The antidote for magnesium sulphate overdose is
10mls of 10% calcium chloride or calcium gluconate given intravenously. The
remedial effect occurs within seconds19.
Diazepam
Intravenous diazepam 10mg given over 1-2 minutes is an acceptable initial
alternative to magnesium sulphate. It is easier to administer, more widely
available, cheaper and quicker acting if convulsion is continuing19.
Diazepam causes respiratory depression, apnea, hypotonia, thermo-regulatory
problems, poor sucking reflex and decreased beat-to-beat rate variability in the
newborn. Also, its sodium benzoate preservative competes with bilirubin for
albumin binding thus predisposing the infant to neonatal jaundice and
kernicterus19.
Other anti convulsants in use include phenytoin and chlormethiazole.
The risk of recurrent convulsions with magnesium sulphate therapy is in the
order of 10-15%, while diazepam about 20%17. Anticonvulsant therapy is continued
for 48 hours after the last fit. And where diazepam is employed it is tailed off
gradually7.
Control of hypertension
Blood pressure is very labile in eclamptics and sensitive to rapid-acting anti-hypertensives.
High blood pressure should be treated urgently but slowly in a gradual fashion.
Antihypertensive is indicated when the diastolic blood pressure is ˇ110mmHg. It
is advisable that diastolic blood pressure should not be lowered by more than
30mmHg or mean arterial pressure by 25% because of risk of iatrogenic utero-placental
hypoperfusion and secondary fetal distress17,19. Diastolic blood pressure should
be maintained preferably between 90 and 100mmHg, combination hypotensive agents
should be avoided since they may have a compound effect. The following drugs can
be used:
Hydralazine
Is the drug of choice for treatment of hypertension in eclamptics. It is a
direct arteriolar vasodilator that causes a secondary baroreceptor-mediated
sympathetic discharge resulting in tachycardia and increased cardiac output.
This increases uterine blood flow and blunts the hypotensive responses making it
difficult to give an overdose19.
A test dose of 5mg intravenously is given slowly over 2-5 minutes to preclude
idiosyncratic reaction, subsequently, 10mg intravenously is given slowly over
5-10 minutes when diastolic blood pressure is ˇ110mmHg. The onset of action is
15 minutes while peak effect occurs within 30-60 minutes and duration of action
is 4-6 hours.
Side effects include flushing, fluid retention, headaches, dizziness,
palpitations, tachyphylaxis, angina and an idiosyncratic lupus like syndrome in
patients when >200mg/day is given19. It also causes neonatal thrombocytopenia2.
Labetalol
This is an alternative first-line drug. It is a non-selective beta-blocker and
post-synaptic alpha adrenergic blocking agent available for both oral and
intravenous use. It reduces blood pressure smoothly and rapidly.
Nifedipine
This is a calcium-channel blocker administered sublingually which can cause
rebound hypotension so it is best avoided in cases of intrauterine growth
restriction and abnormal fetal heart rate patterns.
Other anti-hypertensives in clinical use are diazoxide, sodium nitroprusside,
nitroglycerin and trimethaphan. When blood pressure control is difficult,
co-management with physician is necessary.
Labour and delivery
Timing and Mode of Delivery: Delivery within 6 hours of admission is advocated7
and corroborated by De La Motte who in 17722, recognized that prompt delivery
of pregnant women with convulsions favoured their recovery. Once the patient is
stabilized delivery should be effected either by induction/augmentation of
labour or caesarean section.
Vaginal delivery is preferred except if delivery is not imminent in 6 hours and
in the presence of other obstetric indications for caesarean section17,19.
Regional anaesthesia either epidural or spinal is preferred anaesthesia. Care is
required to avoid hypotension. Regional anaesthesia is contraindicated in
disseminated intravascular coagulopathy. If general anaesthesia is used
important issues are: difficult intubation due to laryngeal oedema; reflex
hypertension associated with endotracheal intubation, airway suctioning and
extubation; risk of aspiration/regurgitation7. Post-caesarean management is best
done in an intensive care unit to reduce the risks of hypoxia, pulmonary oedema,
further convulsions and aspiration.
Labour management: Labour should be managed actively, close fetal heart rate and
maternal vital signs monitoring, assisting the second stage with instrumental
delivery preferably obstetric forceps to minimize bearing down, oxytocin is
recommended for the active management of third stage of labour while ergometrine
is contraindicated. Neonatologist is required at delivery for resuscitation.
Conclusion
An eclamptic episode is a distressing and frightening occurrence and should be
prevented as much as possible. In the absence of an underlying medical problem
such as chronic hypertension and diabetes mellitus, the risk of recurrence is
low. However patients who had atypical eclampsia or continuous seizures despite
anticonvulsant therapy will require neurological follow-up. More research is
required to unravel the aetiology and prevention of this deadly condition.
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