Recent Advances in High Risk Pregnancy Dilip Kumar Dutta
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1Obstetrics Complications2

Pre-eclampsia and EclampsiaCHAPTER 1

PN Nobis
Pre-eclampsia is a commonly encountered disorder during pregnancy. It is a multisystem disorder affecting almost all the vital systems of the body. It is unique to human pregnancy.1 Pre-eclampsia and eclampsia are associated with a high maternal and perinatal mortality and morbidity worldwide. The term pre-eclampsia is used to describe a wide spectrum of patient who may have only mild elevation in blood pressure (BP) or severe hypertension with various organ dysfunction.2 The etiopathogenesis of pre-eclampsia is still illusive and hence management is early detection, symptomatic treatment and delivery at an opportunate time.
Pre-eclampsia is primarily defined as gestational hypertension plus proteinuria.3 Proteinuria is defined as concentration of > 300 mg/24-hour period, or a concentration of 30 mg/dl (1+on dipstik) or more in at least at two random urine samples collected 4 hours apart. The concentration of urinary protein in random urine sample correlate poorly with proteinuria found in 24-hours urine. Therefore, the definitive test to diagnose proteinuria should be quantitative protein excretion in a 24 hour period.2
Edema is not regarded as a criteria for diagnosis of pre-eclampsia. However, sudden appearance of gross edema with hypertension and proteinuria heralds onset of severe pre-eclampsia.
The incidence of pre-eclampsia varies from 3 to 7 percent of all pregnancies. Pre-eclampsia may superimpose in pregnancy with essential hypertension. When pre-eclampsia is superimposed in those cases of chronic essential hypertension blood pressure rises high, there appears significant proteinuria. It is estimated that 25% of hypertensive women develop pre-eclampsia4, while another estimate put it as 70%.2
 
 
Risk Factor for Development of Pre-eclampsia
  • Maternal age < 20 or > 35 years of age.
  • Family history of hypertension, pre-eclampsia, eclampsia
  • Primigravida4
  • Hydatidiform mole
  • Multiple pregnancy
  • Pre-existing hypertension
  • Diabetes mellitus
  • Pre-existing kidney disease
  • Obesity
  • Previous history of pre-eclampsia or eclampsia
  • Fetal hydrops
  • Pre-existing vascular disease, thrombophilia
  • Fetal trisomy.
 
ETIOLOGY AND PATHOPHYSIOLOGY
The etiology of pre-eclampsia is still eluding the obstetricians. In different times several etiological factors have been suggested, but no one could satisfy the scientific world. Few widely discussed theories are mentioned here.
 
PLACENTAL BED
Pre-eclampsia is peculiar to pregnancy. Trophoblast and the placenta with or without a fetus play the central role in the genesis of pre-eclampsia. It is well known that during normal pregnancy trophoblastic cells invade the spiral arteries and brought about vascular changes like breaking down the endothelium, internal elastic lamina and the muscular coat replaced mostly by fibrinoid material.5 These changes take place during the first trimester of gestation. Again in early second trimester there occurs a second wave of trophoblastic invasion transforming the arteries of the myometrial segment. These physiological changes transform the spiral arteries into wide sinusoids, increasing blood supply to the fetus and the placenta. In pre-eclampsia only one half to two-thirds of the spinal arteries undergo these changes and second wave of invasion fail to occur.6 Extent of failure of trophoblastic invasion of the spiral arteries correlate with the severity of hypertension. These typical vascular lesions of the placental bed is termed as “acute atherosis”, because of appearance of foam cell in the vessel wall.7 But it is not specific to pre-eclampsia only. Similar changes are observed in intrauterine growth restriction (IUGR) also. Endothelial damage is observed through out the maternal fetal boundary in decidua outside the placental bed also.8
The reason behind the abnormal placentation is not known. Different suggestions have been put forward. These include reduced expression of histocompetable antigen HLA C, cytokine regulation of integrin expression and local cellular inflammatory reaction.5
 
Oxidative Stress
Another popular theory regarding etiopathogenesis of pre-eclampsia is oxidative stress. The increased production of reactive oxygen species can damage the cell membrane, protein and DNA. Cytokines, tumor necrosis factor α (TNFα) and interleukins contribute to the oxidative stress of pre-eclampsia. It is observed that oxidative stress from reduced placental perfusion lead to endothelial dysfunction in pre-eclampsia.
Nitric oxide is an important free redical. It has an unpaired electron in its outer orbital. The unpaired electron makes the molecule highly reactive and it readily combines with oxygen to produce nitrogen dioxide, a potent oxidizing agent.9 Normally vascular endothelium regulates release of vasoactive substances which control thromboresistance and tone in the vessel wall. Moreover, it inhibits blood coagulation by synthesizing thrombomodulin and heparin sulphate.9 Vascular endothelial dysfunction is likely to be a principal abnormality leading to pathophysiological menifestations of different organ systems. During normal pregnancy, maternal vasculature demonstrates decreased responsiveness to vasoactive peptides like angiotensin II. But in pre-eclampsia vessels show hyper-responsiveness to these hormones. Vascular reactivity and altered coagulation system are result of endothelial dysfunction. The cause of vascular endothelial dysfunction is not clear. It might be that oxidative stress is responsible to a great extent.
Some other factors have also been implicated in the genesis of pre-eclampsia. These are, to name few, platelet activation, circulating lipids, some dietary elements and genetic factor. Circulating lipids have diverse effects on vascular endothelium. Low density lipoprotein (LDL) oxidation may play some role in endothelial dysfunction.10 Several studies have shown platelet activation in association with pre-eclampsia. There occurs increased release of thromboxane, a potent vasoconstrictor prior to onset of the disease. Studies have been conducted to explore relation of dietary deficiency or excess in the genesis of pre-eclampsia. These studies include role of vitamin C and E. Calcium deficiency is thought to cause gestational hypertension.11,12
Calcium supplementation was tried to prevent pre-eclampsia without definite result. Fish oil was given to modify the abnormal prostaglandin balance. But fish oil was also found to be ineffective in preventing onset of pre-eclampsia.13
An inherited maternal component is thought to increase the susceptibility of some women to develop pre-eclampsia,14 wide range of studies have been carried out to find a link between pre-eclampsia and genetic abnormality. But results so far, are in consistent.6
 
Investigation
Complete blood count should be carried out as microangiopathic anemia may be present.
Platelet count is important and a count <100,000/mm3 is significant. It should be repeated twice weekly during the period of observation. When thrombocytopenia is present fibrinogen level, prothrombin time and partial thromboplastin time should be evaluated. Abnormality might be due to disseminated intravascular coagulopathy or consumptive coagulopathy complicating severe pre-eclampsia.
Renal function - there is about 25 percent reduction of glomerular filtration rate (GFR) in pre-eclampsia due to vasospasm and glomerular capillary endothelial swelling. Uric acid level is more sensitive than serum creatinine level. Serum uric acid level of > 5 mg/dl is abnormal.
In hepatic function mild elevation of serum transaminase is common in pre-eclampsia. In early stage bilirubin level is rarely elevated.
 
Classification
Pre-eclampsia can be classified into mild and severe varities. In mild variety blood pressure remain below 160/110 mm Hg. In severe variety systolic blood pressure is 160/110 mm Hg or above recorded at least on two occasions 6 hours apart and the patient being at rest. Blood pressure should be recorded preferably in sitting position or in lying down position with a 30 degree tilt of the body, so that the heart remains at the same level with the BP cuff.
Twenty-four hours urinary protein is ≥ 5 gm and 24 hours urinary output is 400 ml or less. Patient complains of blurring of vision and epigastric pain, nausea and vomiting. Other more serious findings are abnormal liver function tests, thrombocytopenia and pulmonary edema. Liquor volume is usually less (oligohydramnios) with intrauterine growth restricted fetus. Severe pre-eclampsia may lead to eclampsia.
Aspartate aminotransferase (SGOT) and lactate dehydrogenase level may be elevated. Elevated liver enzymes is a part of HELLP syndrome, a severe complication of pre-eclampsia.
Examination of urine for proteinuria by dipstick method is not dependable. If the dipstick test shows proteinuria of ≥ 2+, quantitative estimation of protein in 24 hours collection of urine should be performed. Proteinuria of ≥ 300 mg/day is significant.
 
Management
Termination of pregnancy is the definitive step to cure from pre-eclampsia. The decision to deliver the baby is taken for the best interest of the mother. Few7 factors need consideration before taking the decision to deliver the baby. These are severity of pre-eclampsia, duration of gestation, maternal and fetal conditions.
Management of mild pre-eclampsia: A patient with mild pre-eclampsia can be treated as out patient. However, for proper evaluation of maternal and fetal conditions and for ensuring adequate monitoring these patients may need hospitalization. Adequate monitoring is required because they are at risk of developing severe pre-eclampsia, abruption of placenta. The fetus may be in a compromised state due to reduced utero-placental blood flow and/or intrauterine growth restriction. Hospitalization of a patient with mild pre-eclampsia remote from term enhances fetal survival.
In hospital patient is allowed to take average diet. Sedative or antihypertensive drugs are not used. There is report that use of antihypertensive drug may lead to reduce birth weight.16 Subsequent management depends upon gestational age and maternal response. Monitoring of the mother and the fetus is important during her stay in hospital.
  • Patient is asked to report immediately if she feels headache, visual disturbances or epigastric pain.
  • Blood pressure should be checked every 4 hours during the day.
  • Measurement of weight at least twice weekly to detect sudden excessive weight gain.
  • Urinary output in 24 hours should be measured weekly.
  • Laboratory investigations include measurement of urinary protein, hematocrit, platelet count and liver function test to be repeated twice a week. These investigations are important because thromobocytopenia and abnormal liver function may develop even with mild pre-eclampsia.
 
Delivery
In woman with favorable cervix at or near term labor should be induced with oxytocin drip or with prostaglandin. Pregnancy should not be allowed to continue beyond term. In women with mild pre-eclampsia remote from term pregnancy is allowed to continue till 37 weeks, under strict monitoring, for better fetal survival.
Between 34 to 37 weeks of pregnancy induction of labor is indicated in patients with IUGR, ruptured membrane or in anticipation of fetal jeopardy, evident from monitoring procedures. During the period of observation induction is carried out in patients completing 40 weeks of gestation or after 37 weeks with favourable cervix and when there appears signs of worsening of maternal and fetal condition.
 
For evaluation of fetal condition following are important
  • Daily fetal movement count.8
  • Serial ultrasonography for fetal growth every 3 weeks.
  • Non-stress test and fetal biophysical profile weekly.
 
Severe Pre-eclampsia
Pre-eclampsia is considered to be severe when hypertension above 160/100 mm Hg is associated with proteinuria or hypertension is associated with severe proteinuria i.e. > 5 gm/24 hours urine. Multisystem involvement is usually a feature of severe form of pre-eclampsia. It may be associated with persistent epigastric or right hypochondrial pain from acute enlargement of liver, abnormal liver function tests, oliguria, pulmonary edema and central nervous system symptoms like persistent headache, blurred vision or even temporary blindness. (Box 1.1).
 
Management
Once severe pre-eclampsia is diagnosed patients should be hospitalized, preferably in labor ward. Initial maternal and fetal evaluation is done and decision is taken whether to carry out termination of pregnancy or not. The only cure of pre-eclampsia is termination of pregnancy, however, delay may be made in the interest of the mother or the fetus or both. Every case should be judged on its own merit, keeping in mind the risks involved in continuing pregnancy. The aims of management are:1
  • Prevention of complication like pulmonary edema, intracranial hemorrhage, cardiovascular accident etc.
  • Prevention of eclampsia.
  • Delivery of a healthy baby and to minimize maternal morbidity.
Following initial evaluation patients are managed with magnesium sulphate to prevent convulsion and antihypertensive to lower systolic blood pressure to about 140-155 mm Hg and diastolic BP to 90-105 mm Hg. During the period of observation strict maternal and fetal monitoring to be continued and dicision is9 taken regarding delivery of the baby. To achieve adequate lung maturity of the baby betamethasone 12 mg intramuscularly is administered, two doses 24 hours apart.
 
Magnesium Sulphate for Seizure Prophylaxis
Use of magnesium sulphate as seizure prophylaxis is recommended in diagnosed cases of severe pre-eclampsia. But its use is recommended only during labor and for 12-24 hours postpartum.16 Results of four randomized trials using magnesium sulphate or placebo or no treatment showed significantly lower rate of eclampsia in the group using magnesium sulphate.24,25 Antihypertensive drugs were used in majority of patients in both groups. The Magpie trial25 showed that the low dose magnesium sulphate protocol was more effective to prevent seizure in imminent eclampsia. In this group of patients the number of patients to be treated to prevent one case of eclampsia was 36. And in patients without symptoms of imminent eclampsia the number was 129. In another study, there was 1.5 percent patient develop seizure among 318 pre-eclamptic women who received magnesium sulphate prophylaxis.26 Higher rate of eclampsia in women with severe pre-eclampsia (2%) justifies use of magnesium sulphate prophylaxis.27 In women with mild pre-eclampsia risk of developing eclampsia without magnesium sulphate prophylaxis was 1 in 100 or less.28 Presently owing to lack of adequate evidence in patients with mild pre-eclampsia magnesium sulphate prophylaxis is not recommended.29
The dose schedule of magnesium sulphate for prophylaxis is same as that for treatment of eclampsia. Here the loading dose is not required. In low dose regimen 2 gm magnesium sulphate is administered intravenously slowly. It is repeated every three hourly. The prophylaxis should be continued for further 12 — 24 hours postpartum. Magnesium sulphate can be administered by a controlled intravenous infusion. This method permits better control of the patients blood level and avoids pain of IM injection.15 In intravenous infusion magnesium sulphate is given at a rate of 2 gm in 100 ml of fluid per hour.
 
ANTIHYPERTENSIVE AGENTS
Different antihypertensive agents are available. Among these oral administration of methyldopa, labetalol and long acting nifedepine are accepted as drug of choice for hypertensive pregnant women.17,18 Of course, in developed countries hydralazine is used extensively.
Methyldopa: Methyldopa is the drug of first choice.19 It is effective and has best maternal safety. It is a centrally acting drug. The usual initial dose is 250 mg, orally, three times a day. Dose can be increased to four times a day, maximum daily dose should not exceed 3 gm/day.2010
Nifedepine: Nifedepine is a calcium channel blocker and is used extensively during pregnancy. It exerts its antihypertensive effect by vasodilatation by relaxation of smooth muscles. The dose of slow release tablets is 20-30 mg orally, four times a day, not to exceed 120 mg/day. Capsules of 10-30 mg, orally, thrice a day can be given for fast action. Maximum dose should not exceed 120 mg/day. If there is no substantial decrease in BP another 10 mg capsule can be given after 30 minutes. Concomitant use of nifedepine and magnesium sulphate may lead to transient neuromuscular weakness.21,22
Labetalol: Labetalol is a combination of alpha and beta-adrenoceptor. It is a peripheral vasodilator and is an effective antihypertensive in pre-eclampsia. The usual oral dose is 100 mg thrice a day up to a maximum of 800 mg/day. Labetalol and methyldopa administered orally was found to be effective in significantly lowering blood pressure compared with no medication.20 For lowering severe blood pressure in severe pre-eclampsia or eclampsia intravenous labetalol 20 mg can be administered, increasing the dose to 40 mg or even 80 mg every 30 minutes, if required. Maximum dose should not exceed 200 mg/day. It is contraindicated in hepatic disorder. There is risk of neonatal hypotension, oliguria and bradycardia with parenteral labetalol.23
Hydralazine: To treat severe hypertension in pre-eclampsia intravenous hydralazine is being used for a long time. In this situation this is regarded as a drug of first choice.17,18 The dose is 5 mg given slowly intravenously, can be repeated after 20 minutes with 10 mg, if needed, the total dose being 20 mg. Blood pressure should be checked every 5 minutes. Intramuscularly, 10-20 mg can be given every 4-6 hours. The dose can be increased to 40 mg. Side effects are headache, nausea and vomiting. Clinical trial showed that maternal hypotension may be more common with parental hydralazine.23
 
Severe Pre-eclampsia at or after 34 weeks of Pregnancy
Clinical course of severe pre-eclampsia may deteriorate jeopardizing both maternal and fetal condition. These patients should be delivered at 34 weeks of pregnancy. Fetal lung maturity should be ensured before delivery, if needed betamethasone should be administered. Delivery is also indicated in rupture of membrane, labour and severe IUGR.15
 
Patients before 24 weeks of Pregnancy
In this group of patients perinatal survival rate is very low.3032 So, in patients developing severe pre-eclampsia before 24 weeks of pregnancy, termination of pregnancy is recommended. Labour should be induced and maternal condition is closely monitored during labor.11
 
Patients Presenting between 24 and 34 weeks of Pregnancy
Opinion differs as to management of patients with severe pre-eclampsia between 24 and 34 weeks of gestation. Some workers favour termination of pregnancy irrespective of period of gestation. The other group favors conservative management to prolong pregnancy until maternal or fetal indication for delivery, fetal lung maturity is achieved or at 34 weeks of gestation.2 Patients for conservative management in severe pre-eclampsia should be selected carefully. Moreover, proper counseling of the patient and her husband is required. Patients should be admitted in tertiary care center with facilities for adequate intensive care. Patients are treated with magnesium sulphate, antihypertensive drugs and frequent monitoring of maternal and fetal condition. With expectant treatment neonatal survival rate was 65 percent compared with 24 percent in termination of pregnancy following steroids, to achieve fetal lung maturity.15 With expectant management prolongation of pregnancy was achieved from 2-35 days, the median number of days prolonged was 7 day.33
Mode of delivery depends on period of gestation, fetal condition, presence of labour and cervical Bishop score. Vaginal delivery should be attempted in all women with mild pre-eclampsia and in majority of the women with severe disease particularly when the period of gestation is beyond 30 weeks.17 Elective cesarean section should be considered for women with severe pre-eclampsia below 30 weeks of gestation, not in labour, fetal growth restriction and with unfavorable cervix at less than 32 weeks of gestation. During vaginal delivery second stage of labour should be cut short with obstetric forceps or ventouse. Methyl ergometrin should be avoided during the third stage of labor.
 
Maternal Outcome in Pre-eclampsia
Severe pre-eclampsia is associated with maternal mortality rate of 0.2 percent and morbidity rate of 5 percent.2 Eclampsia is a major complication of pre-eclampsia. Increased mortality and morbidity may be again due to cardiovascular accident, pulmonary edema, HELLP syndrome, acute renal failure, disseminated intravascular coagulation etc. These complications are more common in early onset pre-eclampsia.16
 
Perinatal Outcome in Pre-eclampsia
Perinatal mortality and morbidity in severe pre-eclampsia are very high. The causes of increased mortality and morbidity of the neonates are intrauterine growth restriction, prematurity, abruptio placentae and even intrauterine fetal death. Rate of operative delivery is more due to increased rate of induction of labour.1612
Perinatal outcome also depends on the period of gestation during the onset of the disease. Perinatal outcome is worse in early onset pre-eclampsia. In mild form of the disease perinatal outcome is almost similar to those in normotensive pregnancy.
 
ECLAMPSIA
Eclampsia is defined as the development of convulsion and/or unexplained coma during pregnancy or postpartum in patients with signs and symptoms of pre-eclampsia.29 Its occurrence varies widely. Reported incidence of eclampsia in Western world is from 1 in 2000 to 1 in 3448 pregnancies.34,35 In India reports from different hospitals quote a higher incidence ranging from 0.5 to 3.7%.3638 In about 90% of the cases eclampsia develop during the third trimester of pregnancy and within 48 hours of delivery. Rarely eclampsia may develop before 20 weeks of gestation, specially in cases with hydatidiform mole and as late as 23 days postpartum.2
The cause of eclampsia is unknown. To explain the neurological manifestations brain imaging is carried out. Findings of these studies show evidence of vasogenic edema of brain. This suggests that hypertensive encephalopathy plays central role in causation of convulsion in eclampsia.29
 
Diagnosis
Diagnosis of eclampsia is not difficult when there is convulsion in a pregnant woman with hypertension, proteinuria and generalized edema. Women developing eclampsia may present with varied signs and symptoms. There may be severe hypertension, severe proteinuria and generalized edema or there may be absent or minimal hypertension, no proteinuria or no edema.39 Hypertension may be severe in 20-54 percent of cases,35,40 while there may be no hypertension in 16 percent of cases.40 Severe proteinuria is present in about 48 percent of cases and there may be no proteinuria in 26 percent of cases.
Other symptoms like persistent frontal headache, blurred vision, epigastric or right hypochondrial pain, altered mental status may occur even after onset of seizure. At least one of these symptoms are present in about 59-75 percent of patients with eclampsia.
 
TYPE OF ECLAMPSIA
Eclampsia is described as antepartum, intrapartum and postpartum. Antepartum eclampsia is reported to range from 38 to 53 percent and postpartum eclampsia ranged from 11 to 44 percent.35,40,42 Patients with late postpartum eclampsia13 should have extensive neurological evaluation to rule out cerebral pathology. Similarly eclampsia developing at or before 20 weeks of gestation is likely to create confusion in diagnosis. Other condition simulating eclampsia are hypertensive encephalopathy, other convulsive disorders and thrombotic thrombocytopenic purpura. In a pregnant women when convulsion develops in association with hypertension and proteinuria should be diagnosed as eclampsia and treated accordingly until proved otherwise. Same should be the policy in late postpartum eclampsia also.42,43 In these two types of atypical eclampsia cerebral imaging like CT scan or MRI is helpful to exclude any cerebral pathology. Imaging is also indicated for patients with focal neurological deficit or prolonged coma.2
 
Management
A woman with eclampsia should be managed in a tertiary level hospital. The objectives for management of eclampsia include:
  • Control of convulsion.
  • Prevent further convulsion.
  • Control of blood pressure.
  • Delivery after adequate stabilization of the patient.
During or immediately after a convulsive episode care should be taken to prevent maternal injury, proper maintenance of airway, to prevent aspiration of vomitus or secretion and to ensure maternal oxygenation. Care to be taken during or immediately after a convulsion
  • Put the patient in left lateral position. This position prevents aspiration of vomitus, if vomiting occurs or oropharyngal secretion.
  • Airway is secured, if needed with nasogastric suction
  • Administer oxygen with a face mask.
  • Padded tongue blade to be introduced to prevent tongue bite.
  • Bed's side rails should be elevated to prevent maternal injury.
  • Pulse oxymetry should be used to monitor oxygenation in the patient.
  • Wide bore peripheral intravenous line should be started to administer anticovulsant.
  • Anticovulsant administered to prevent further convulsion.
 
Anticonvulsant
In the past few drugs like Lytic Cocktail, Diazepam, Phenytoin sodium were used to control convulsion in eclampsia. Presently magnesium sulphate is accepted world wide as the anticonvulsant of choice.4446 And subsequently findings of the Collaborative Eclampsia Trial confirmed the superiority of magnesium sulphate over phenytoin and diazepam in management of convulsion in eclampsia.4714
 
Dosage of Magnesium Sulphate
Different dosage schedule have been suggested by different workers (Table 1.1).
Table 1.1   Magnesium sulphate regimens
Pritchard et al44
Loading dose
:
4 gm as 20% solution IV, 1 gm/min
Maintenance
:
5 gm IM 4 hourly
Zuspan et al48
Loading dose
:
4 gm IV over 3-5 mins
Maintenance
:
1-2 gm/hour, IV
Sibai46
Loading dose
:
6 gm IV over 20 mins
Maintenance
:
2 gm/hour IV
If there is recurrence of convulsion a bolus dose of 2 gm magnesium sulphate is administered IV over 3-5 minutes. In ten percent of cases there may be recurrence of convulsion.29 In rare cases if convulsion continues sodium amobarbital 250 mg may be given intravenously over a period of 3-5 mins.29 Sodium amobarbital should be administered very carefully with arrangement for intubation and positive pressure ventilation, preferably in presence of an expert anesthetist. The maintenance therapy is continued for 24 hours after delivery or the last convulsion.
The exact dose of magnesium sulphate to control and then to prevent further convulsion is not ascertained. There is controversy regarding the “therapeutic” dose and the serum level suggested by different workers varies between 3-6 mg/dl and 2-4 m mol/l.14 So, routine use of serum level of magnesium is not recommended, except in cases of renal dysfunction and absent reflexes.29 It was proposed by Pritchard that the dose of magnesium sulphate should be limited in women of small size. In view of the smaller size and less weight of an average Indian woman a modified low dose regimen is tried with equally effective results.49
 
Magnesium Sulphate Toxicity
Magnesium sulphate is excreted in urine, so, urinary output should be measured accurately. In therapeutic dose magnesium sulphate slows neuromuscular conduction and thereby, depresses central nervous system irritability. Maternal respiratory rate, deep tendon reflex and state of consciousness must be monitored frequently. Table 1.2 shows the manifestations of magnesium sulphate toxicity with plasma level of magnesium sulphate.2
 
Management
  • Discontinue MgSO4
  • Obtain magnesium serum level
  • If magnesium level > 15 mg/dl give 1 gm calcium gluconate IV15
    Table 1.2   Magnesium sulphate toxicity
    Manifestations
    Plasma level
    Loss of patellar reflex
    8-12 mg/dl
    Feeling of warmth, flushing
    9-12 mg/dl
    Somnolence
    10-12 mg/dl
    Slurred speech
    10-12 mg/dl
    Muscular paralysis
    15-17 mg/dl
    Respiratory difficulty
    15-17 mg/dl
    Cardiac arrest
    30-35 mg/dl
  • Intubation
  • Assist ventilation
In presence of renal insufficiency care should be taken in administering MgSO4 and frequent monitoring is required. In case of intramuscular administration of MgSO4 the following to be monitored before each injection.
  • Patellar reflex - present
  • Respiration rate- 16 or more/minute
  • Urine output during the previous 4 hours is 100 ml or more.
Other anticonvulsants which were used to control convulsion in eclampsia include lytic cocktail, phenytoin sodium and diazepam. Presently these drugs are not used as magnesium sulphate is shown to be a superior alternative.
 
Dosage
Diazepam—Initially 10-20 mg intravenously slowly over a period of 1-2 minute, then 40 mg in slow intravenous infusion. In case of recurrence of convulsion another 10-20 mg IV slowly.
Phenytoin sodium—Initially 600 mg of phenytoin sodium diluted in 200 ml of normal saline or 5% dextrose and administered slowly intravenously over a period of 25-30 minutes. Followed by 100 mg IV slowly every 6 hours for 24 hours.
 
Control of Hypertension
In a woman with eclampsia blood pressure should be lowered to a safe level. It should not be lowered too rapidly as there may be reduction in cerebral perfusion pressure and reduction in uteroplacental blood flow increasing fetal jeopardy.1,29 The systolic blood pressure should be lowered to 140-150 mm Hg and diastolic pressure to 90-100 mm Hg. To bring the blood pressure to a desired level hydralazine 5-10 mg intravenously or labetalol 20-40 mg intravenously is administered, if there is tachycardia. Labetalol can be given in infusion 120 micro gm/min. Hydralazine can be repeated every 15 minutes as needed.16 As16 an alternative nifedepine is given orally every 30 minutes for a maximum dose of 50 mg in one hour. Other antihypertensive agents like diazoxide, sodium nitroprusside and nitroglycerine are rarely needed in an eclamptic patient. The only indication of diuretics in eclampsia is presence of pulmonary edema.
Careful monitoring of intravenous fluids used in pre-eclampsia and eclampsia is needed. Intake and output chart should be maintained and assessed frequently. Ringer lactate solution is used routinely. Amount of fluid infused depends on urinary output. There should be 100 ml or more urine output in 4 hours period. If urinary output during this period is less than 100 ml the dose of MgSO4 and intravenous fluid should be reduced. Care should be taken to avoid circulatory overload. Ringer's lactate is recommended at a rate of 100 ml/hour.1
 
Delivery
Following stabilization of the patient with eclampsia delivery should be planned. Before deciding the mode of delivery the factors to be considered are gestational period, fetal condition in utero, Bishop score and whether the patient is in labor or not. The obstetrician should take the decision regarding the mode of delivery considering the risks involved and the benefits for both the mother and the child. Patients in labour or with ruptured membranes are allowed to deliver vaginally. In other patients with gestational age of 30 weeks or more are also planned for vaginal delivery, labour should be induced with oxytocin drip or prostaglandin. In another group of patient with gestational age less than 30 weeks but with Bishop score of more than 5, labour should be induced.
Eclampsia per se is not an indication of cesarean section. It is indicated in situations like patients with other indication for cesarean section, vaginal delivery is unlikely to occur within 6-8 hours of first convulsion and fetal distress. Eclampsia developing before 30 weeks of gestation is prone to have IUGR, abruptio placentae and fetal distress during labour. These patients are better delivered by elective cesarean section.15
During a convulsion maternal hypoxia occurs and leads to hypercarbia. Both hypoxia and hypercarbia bring about some changes in fetal heart rate pattern and in uterine activity.50 Altered fetal heart rate pattern include bradycardia, transient late deceleration, decreased beat-to-beat variability and compensatory tachycardia. Changes in uterine activity include increased frequency of uterine contraction and increased tone. These are temporary changes and resolve within 3-10 minutes after cesation of convulsion. However, if bradycardia and/or recurrent late bradycardia persist more than 10-15 minutes fetal jeopardy is warranted.17
During vaginal delivery second stage of labour should be cut short and methylergometrine is better avoided in third stage of labor.
Regional anesthesia like spinal or epidural anesthesia is favored by many. Regional anesthesia is contraindicated in presence of coagulopathy or severe thrombocytopenia. In an eclamptic woman general anesthesia increases the risk of aspiration or failed intubation due to laryngeal edema.
 
Care after Delivery
After delivery an eclamptic patient should be kept under close observation. During this period the vital signs, fluid intake and output and other symptom should be observed for at least 24 hours. Patient with abnormal renal function and having abruptio placentae are prone to develop pulmonary edema, mostly due to intravenous fluid infusion and shifting of fluid from extracellular compartment to intravascular compartment. Magnesium sulphate should be continued for at least 24 hours after delivery or after the last convulsion. Antihypertensive drug should be started again according to BP.
 
Maternal and Perinatal Outcome
Eclampsia is associated with high maternal and perinatal mortality and morbidity. In developed countries maternal mortality ranges from 0-1.8%,35,40,41,44 while in India it ranges from 2.63 to 14%.36,41,47,49,51 The risk of death from eclampsia is higher in women older than 30 years of age, early onset of eclampsia, multiple convulsion, women of low socioeconomic condition and with no antenatal care. The main causes of death are cardiovascular accident, pulmonary edema, abruptio placentae and HELLP syndrome. Similarly causes of high morbidity are abruptio placentae, pulmonary edema, acute renal failure, disseminated intravascular coagulation and aspiration pneumonia.35,40
Perinatal mortality and morbidity are also high in eclampsia. In developed countries perinatal mortality ranges from 5.6 to11.8%.35,39 The reported mortality in India ranges from 18 to 40%.47,49,51,52 High rate of mortality is related to prematurity, birth asphyxia, IUGR and abruptio placentae.
 
HELLP SYNDROME
HELLP syndrome is a variant of pre-eclampsia. This is characterized by hemolysis, elevated liver enzymes and low platelet count. Platelet count of >100,000/mm3 is the most consistent finding in HELLP syndrome. This syndrome occurs in about 2-12% of pre-eclamptic patient1 and in about 30% patients with eclampsia.1518
 
Criteria for Diagnosis of HELLP Syndrome2
Hemolysis (at least two of these findings)
Peripheral smear (schistocytes, burr cell)
Serum bilirubin (>1.2 mg/dl)
Low serum heptoglobin
Severe anemia unrelated to blood loss
Elevated liver enzymes
AST or ALT > twice upper limit of normal
LDH > twice upper limit of normal
Low platelet count.
 
Maternal and Perinatal Outcome
Presence of HELLP syndrome further deteriorate the maternal and perinatal outcome. Reported maternal mortality is about 1% and perinatal death rate ranges from 7.4 to 20.4%.2
 
Management
Management of woman with HELLP syndrome is same as for severe pre-eclampsia. Patient should be delivered at any gestational period. After initial assessment patient should be stabilized coagulopathy, if any, should be corrected before attempt to deliver. Sometimes delivery may be delayed by 24-48 hours for administration of corticosteroid for lung maturity of the baby. All patients with HELLP syndrome should be followed up with repeated platelet count. Platelet count should be maintained greater than 20,000/mm3 for vaginal delivery and 40,000/mm3 for cesarean section.2 To increase platelet count platelet transfusion may be required. Post delivery monitoring is same as in severe pre-eclampsia.
 
REMOTE PROGNOSIS
Long-term follow up of women who developed pre-eclampsia/eclampsia do not show increase in hypertension among them. Pre-eclampsia/eclampsia does not cause hypertension who were normotensive before the eclamptic pregnancy.15 However, recurrent pre-eclampsia and eclampsia in subsequent pregnancies were found to be 22% and 1-1.9% respectively.53,54 The incidence of pre-eclampsia and eclampsia is much higher in subsequent pregnancies in women who had eclampsia remote from term.
 
Prevention
We do not know the cause of pre-eclampsia and eclampsia. Hence our efforts of prevention are limited. All we can do is close monitoring of the pregnant woman with high risk factors for development of pre-eclampsia. There is no medication19 to prevent pre-eclampsia. Once the disease is detected, medications are needed to control blood pressure and to prevent eclampsia in diagnosed cases. During the last few years different pharmacological agent and food supplementations are tried to prevent pre-eclampsia. These include low dose aspirin, use of protein, zinc, magnesium, calcium, vitamin C and E and fish oil supplementation. But the results showed minimal or no benefit in preventing pre-eclampsia.13 Presently to prevent development of eclampsia in a diagnosed case of pre-eclampsia much stress is given on early detection of gestational hypertension or pre-eclampsia. Use of antihypertensive drugs to keep the blood pressure under control, finaly delivery and use of prophylactic magnesium sulphate during labour and immediately after delivery.16 Prophylactic magnesium sulphate is effective in preventing approximately 50% of the cases of developing eclampsia in diagnosed cases of pre-eclampsia.29
Pre-eclampsia and eclampsia are major causes of increased maternal and perinatal mortality in India. Preventive measures are also not very helpful. Early detection of gestational hypertension or pre-eclampsia is the mainstay to improve the maternal and perinatal outcome. It is essential to improve public health facilities, female education and improvement in socio-economic standards. In hospitals every maternity unit should have a well formulated management protocol with intensive care unit for both the mother and the child.
REFERENCES
  1. Paruk F, Moodely J. Treatment of severe pre-eclampsia/eclampsia syndrome. Progress in Obstetrics & Gynaecology. 14, Edited by John Studd. Philadelphia  Churchill Livingstone;  2000;(14)102–19.
  1. Labib M, Sibai BM. Gestational Hypertension - pre-eclampsia and eclampsia. Management of High Risk pregnancy. 5th Ed.;Blackwell Publishing Ltd.  Machachusetts  2007;271–79.
  1. Sibai BM. Diagnosis and management of gestational hypertension and pre-eclampsia. Obstet Gynecol 2003;102:181–92.
  1. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289(19):2560–72.
  1. Bronsen I, Dixon HG. The Anatomy of the maternal side of the placenta. J. obstet Gynecol Br Commow 1966;73:357–63.
  1. Khong TY, de Wolf F, Robertson WB, et al. Inadequate maternal vascular response to placentation in pregnancies complicated by pre- eclampsia and by small for-gestational age infants Br J Obstet Gynecol 1986;93:1049–59.
  1. Labarrere CA. Acute Atherosis: a histopathological landmark of immune aggression. Placenta 1988;9:95–108.
  1. Shanklin DR, Sibai BM. Ultrastuctural aspect of Pre-eclampsia. Am J obstet Gynecol 1 1989;61:735–41.
  1. Morris NH, Eaton BM, Dekker G. Nitric Oxide, the endothelium, pregnancy and pre-eclampsia. Br J Obstet Gynecol 1996;103:4–15.

  1. 20 Desai PD. Reducing systems in pre-eclampsia Recent Advances in Obstet and Gynaecolgy, Jaypee Brothers Medical Publishers (P) Ltd.  New Delhi,  2003:79–98.
  1. Leela R, Yasodhara P, Ramaraja LA. Calcium and magnesium in pregnancy. Nutr. Res. 1991;11:1231–36.
  1. Prada JA, Ross R, Clark KE. Hypocalcemia and pregnancy induced hypertension produced by maternal fasting. Hypertension 1992;20:620–26.
  1. Sibai BM. Prevention of Pre-eclampsia: a big disappointment. Am J Obstet Gynecol 1998,179:1275–78.
  1. Greer IA. Pregnancy induced hypertension. In Turnbull's Obstetrics. 3rd Ed. Churchill Living stone,  London.  2002;333–53.
  1. Sibai BM. Hypertension in Pregnancy. Obstetrics. Normal and problem pregnancies. 4th Ed. Churchill Livingstone,  Philadelphia, PA  2002;573–96.
  1. Sibai B. M. Diagnosis and management of gestational hypertension and pre-eclampsia. Obstet Gynecol 2003;102:181–92.
  1. Report of the National High Pressure Education Program. Working group report on high blood pressure in pregnancy. Am J Ob stet Gynecol 2000;183:S1–S22.
  1. Brown MD, Haque WM, Higgins J, et al. The detection, investigation and management of hypertension in pregnancy executive summary. Aus NZ J Obstet Gynecol 2000;40: 133–8.
  1. Magee LA. Treating hypertension in women of child bearing age and during pregnancy. Drug safety 2001;24(6):457–74.
  1. Sibai BM, Mabie WC, Shamsa E, et al. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Am J Obstet Gynecol. 199;162(4):960–66.
  1. Ben AM, Giladi Y, Shalev E. The combination of magnesium sulphate and nifedepine, a cause of neuromuscular blockade. Br J Obstet Gynecol 1994;101:262–3.
  1. Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulphate and nifedepine. Br J Obstet Gynecol 1989;161:35–36.
  1. Magee LA, Ornstein MP, Von Dadelszen P, Fortnightly review: management of hypertension in pregnancy. BMJ 1999;318:1332–36.
  1. Sibai BM. Magnesium sulphate prophylaxis in pre-eclampsia: lessons learned from recent trials Am J Obstet Gynecol 2004;1901520–26.
  1. The Magpie Trial Collaborative group. Do Women with pre-eclampsia and their babies benefit from magnesium sulphate? The Magpie Trial: a randomized placebo - controlled trial.   Lancet  2002;359:1877–90.
  1. Hall DR, Odendaal HJ, Smith M. Is the prophylactic administration of magnesium sulphate in women with pre-eclampsia indicated prior to labour. Br J Obstet Gynecol 2000a;107:903.
  1. Rozenberg P. Magnesium sulphate prophylaxis in pre-eclampsia. Gynecol Obstet Fertil. 2006.
  1. Lucas MJ, Leveno KJ, Cunninghum FG. A comparison of magnesium sulphate with phenytoin for the prevention of eclampsia. N Eng J Med 1995;333:201.
  1. Sibai BM. Diagnosis, Prevention and Management of Eclampsia. Obstet & Gynecol. Clinical expert Series and current commentaries; Year Book 2005;1–9.
  1. Oden dall HJ, Pattinson RC, Du Toit R. Fetal and neonatal outcome in patients with severe pre-eclampsia before 34 weeks. S Afr Med J 1987;71:555–58.
  1. Sibai BM, Taslima M, Abdella TN, et al. Maternal and Perinatal outcome of conservative management of of severe pre-eclampsia in the mid-trimester. Am J Obstet Gynecol 1985:152:32–37.

  1. 21 Moodely J, Korateng SA, Rout C. Expectant management of early onset of severe pre-eclampsia in Durban, South Africa. S Afr Med J 1993;83:584–87.
  1. Haddad B. Expectant management of severe pre-eclampsia remote from term. Clin Obstet Gynecol 2005;48:430–40.
  1. Saftlas AF, Olson DR, Franks AC, at al. Epidemiology of pre-eclampsia and eclampsia in the United States. 1979-1986 Am J Obstet gynecol 1990;163:460–65.
  1. Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ 1994;309:1395–400.
  1. Nobis PN. Maternal Outcome in Eclampsia Asian J Obset Gynecol Practice 2002;1(6):25–28.
  1. Suman G, Somegowda S. Maternal and perinatal outcome in eclampsia in a district hospital, J Obstet Gynecol, India 2007, 57,4: 324–326.
  1. Samel S, Gupta U, Agarwal P. Management of eclampsia with magnesium sulphate and Nifedepine. J Obstet Gynecol India 2001;51(3):71–74.
  1. Sibai BM. Eclampsia VI. Maternal and perinatal outcome in 254 consecutive cases. Am J Obstet Gynecol 1990;163:1049–55.
  1. Mattar F, Sibai BM. Eclampsia VIII Risk factor for maternal morbidity. Am J obstet Gynecol 2000;182–307–12.
  1. Katz VL, Farmer R, Kuller J. Pre-eclampsia into eclampsia: toward a new paradigm. Am J obstet Gynecol 2000;182:1389–96.
  1. Chames MC, Livingston JC, Invester TS, et al. Late postpartum eclampsia: a preventable disease? Am J Obstet Gynecol 2002;186:1174–77.
  1. Lubarsky SL, Barton JR, Friedman SA, et al Late post partum eclampsia revisited. Obstet Gynecol 1994;83:502–05.
  1. Pritchard JA, Pritchard SA, Cunningham FG. The Parkland Memorial Hospital protocol for treatment of eclampsia: Evaluation of 245 cases. Am J Obstet Gynecol 1984;148:951.
  1. Domissee J. Phenytoin sodium and magnesium sulphate in the management of Eclampsia. Brit J Obstet Gynecol 1990;97:104–109.
  1. Witlin AG, Sibai BM. Magnesium sulphate in pre-eclampsia and eclampsia. Obstet Gynecol 1998;92:883–9.
  1. Doley L, Carroli G, Belijan J, et al. Which articonvulsant for women with Eclampsia? Evidence from the collaborative Eclampsia Trial Lancet 1995:345:1455–69.
  1. Zuspan FP. Problems encountered in the treatment of pregnancy induced hypertension. Am J Obstel Gynecol 1978;131:591–96.
  1. Sardesai S, Maira S, Patil A et al. Low dose magnesium sulphate therapy for eclampsia and imminent eclampsia, Regime tailored for Indian women. J Obstet Gynecol India. 2003;53(6):546–50.
  1. Paul RH, Kee Sk, Bernstein SG. Changes in fetal heart rate and uterine contraction pattern associated with eclampsia. Am J Obstet Gynecol 1978;130:165–9.
  1. Gupta G, Gupta Ch, Manhas K. A comparative study of Magnesium Sulphate and lytic cocktail therapy in managemnt of eclampsia. Asian J Obstet Gynec practice 2009;7(3&4):34–37.
  1. Nobis PN. Perinatal mortality in eclampsia. The J obstet Gynecol India 1988;38(1)38–42.
  1. Sibai BM, Sarinoglu C, Meror BM et al. Eclampsia VII Pregnancy outcome after eclampsia and long-term Prognosis. Am J Obstet Gynecol 1992:166;1757–63.
  1. Chesley LC. Remote prognosis: Hypertensive disorders in pregnancy Appleton -century Craft. New York; 1978;421–43.