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Intensive Care Management of Severe Pre-eclampsia and Eclampsia
Review Article
INTENSIVE CARE MANAGEMENT OF SEVERE PRE-ECLAMPSIA AND ECLAMPSIA V. Murlidhar* and Sameer Bolia** Senior Consultant*, Senior Resident**, Department of Anaesthesia, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. Correspondence to: Dr. V. Murlidhar, Senior Consultant, Department of Anaesthesia, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. Pregnancy induced hypertension is a common medical complication of pregnancy and is a significant contribution to maternal and perinatal morbidity and mortality. Early diagnosis, increased patient awareness and appropriate medical intervention, especially intensive care management of severe preeclampsia and eclampsia have led to marked fall in mortality in this group of patients. In this review article, the pathophysiology, effect on different organ systems, choice of drugs (anticonvulsants and antihpertensives), support of a critically ill patient in the intensive care, monitoring, anaesthetic considerations and management of the neonate are discussed. Key words: Intensive care, Pre-eclampsia, Eclampsia, Pregnancy induced hypertension, anticonvulsants, HELLP syndrome, Convulsions.
INTRODUCTION HYPERTENSIVE disorders are the most common medical complication of pregnancy[1,2]. Two basic types of hypertension occur during pregnancy: chronic hypertension and pregnancy-induced hypertension (PIH). Chronic hypertension is that which predates pregnancy or continues beyond 42 weeks postpartum. Pregnancy-induced hypertension generally occurs after 20 weeks of pregnancy. Clinically chronic hypertension and pregnancy-induced hypertension (PIH) may coexist. Further, PIH is classified according to the maternal organ systems affected. Preeclampsia is the progression of PIH and is classified as severe or mild based on maternal and fetal clinical findings (Table 1). Eclampsia is defined as the development of convulsions and/or unexplained coma during pregnancy or postpartum in patients with signs and symptoms of pre-eclampsia. In the western world, the reported incidence of eclampsia ranges from 1 in 2,000 to 1 in 3,448 pregnancies. The reported incidence is usually higher in tertiary referral centres, in multifetal gestation, and in populations with no prenatal care[3,4]. Current definitions place less reliance on the presence of pre-eclampsia as eclampsia can develop without preceding symptoms or signs in up to 38% of cases.extra. Late postpartum eclampsia is defined as eclampsia that occurs more than 48 hours, but less than 4 weeks, after delivery[5]. The cause is a pregnancy specific, underlying multiorgan disorder involving vascular endothelial damage, intravascular coagulation, and vasoconstriction leading to Apollo Medicine, Vol. 3, No. 1, March 2006
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end organ ischaemia. There may be a variety of presentations and classic features are not always present. Changes have occurred in the recommended treatment for eclamptic seizures and are considerably different from other seizure disorders (including management of hypertension and careful fluid balance). INCIDENCE, MORTALITY AND MORBIDITY A significant contributor to maternal and perinatal morbidity and mortality[6,7], hypertension is estimated to complicate approximately 7-10% of all pregnancies[8]. In the developing and underdeveloped world, the incidences are thought to be 20 times more than in the developed world. Eclampsia is responsible for approximately 50,000 maternal deaths worldwide each year. A prospective descriptive survey of every case of eclampsia in the UK was carried out in 1992[9]. Two hundred and seventy nine consultant led obstetric units were surveyed. Five hundred and eighty two possible cases were reported and 383 were subsequently confirmed as cases of eclampsia. This gave a rate of 4.9 per 10 000 maternities. This incidence is similar to that reported in the USA in 1983-1986 of 4.3 per 10 000 [10]. Sixty eight per cent of seizures occurred in hospital; 44% were postpartum; 18% were intrapartum. The remainder were antepartum. A recent study at the All India Institute of Medical Sciences (AIIMS) shows the incidence of toxaemia including eclampsia to be 16.4% (1995-1997) in 46,443 admissions (116 maternal death)[11]. A study at
Review Article
Table 1: Features under mild and severe pre-eclampsia. Abnormality
Mild
Severe
Diastolic blood pressure
<100
>110 or higher
Proteinuria
Trace to 1+
Persistent 2+ or more
Headache
Absent
Present
Visual disturbances
Absent
Present
Upper abdominal pain
Absent
Present
Oliguria
Absent
Present
Convulsions
Absent
Present (eclampsia)
Sr. creatinine
Normal
Elevated
Thrombocytopenia
Absent
Present
Liver enzymes elevation
Minimal
Marked
Fetal growth restriction
Absent
Obvious
Pulmonary edema
Absent
Present
Safdarjung Hospital (1975-84) studied the various causes of maternal mortality and morbidity between 1975 to 1984 and came up with the following facts: (a) Mortality rate of eclampsia was 7.05/1000 births (197584); (b) Rising eclampsia mortality from 10.2% (1975) to 15.02% (1984). Managing them in an intensive care unit (1984-86) led to a marked fall in mortality [12]. This is supported by a number of studies and it is mandatory to manage severe pre-eclampsia and eclampsia in the ICU. Eclampsia and pre-eclampsia continue to be responsible for very high morbidity and mortality in the developing world due to inadequate antenatal care, absence of a referral network and management in ill-equipped centres. Pregnancies complicated by eclampsia are also associated with increased rates of maternal morbidities [13], such as abruptio placentae (7-10%), disseminated intravascular coagulopathy (7-11%), pulmonary edema (3-5%), acute renal failure (5-9%), aspiration pneumonia (2-3%), and cardiopulmonary arrest (2-5%). Adult respiratory distress syndrome and intracerebral haemorrhage are rare complications among eclamptic series reported from the developed world. The risks of diffuse intravascular coagulation (8%); haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (10-15%); and liver haematoma (1%) are similar in eclamptic and severely preeclamptic patients. It is important to note that maternal complications are significantly higher among women who develop antepartum eclampsia, particularly among those who develop eclampsia remote from term.
OBJECTIVES OF INTENSIVE CARE MANAGEMENT 1. Organ support and management of multiorgan failure 2. Prevention and management of the critical incidents such as airway obstruction, aspiration etc. 3. Medical and obstetric management of a potentially reversible and manageable state 4. Neonatal management The understanding of the disease has changed considerably in the last two decades. It was realized that early shifting of these patients to an intensive care unit led to a drastic fall in the mortality and morbidity. The question arises at what point of time these patients should be shifted to an intensive care unit. Sengupta, et al[12] were using the criteria of (a) severe hypertension, (b) prolonged unconsciousness, (c) multiple convulsions, (d) respiratory distress and respiratory failure. But these criteria have expanded with the understanding of the disease and have grown to include hepatic and renal problems. Even signs of cerebral irritation should be considered a warning sign and necessitate close monitoring. The individual predictive value of these risk factors for risk identification has been questioned. In a recent study Nisell, et al have identified factors predicting maternal and fetal complications[14]. The only factor, which they found to be of predictive value, was diastolic blood pressure. Severe pre-eclampsia and eclampsia need to be referred and managed in a well-equipped center. The center should have facilities to diagnose and define the disease and its complications. It should have facilities to intensively manage various problems, e.g., ICU with facilities for
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management of the critically ill patients, operation theatre, a well-equipped blood bank and neonatal intensive care. PATHOPHYSIOLOGICAL BASIS OF CRITICAL CARE IN SEVERE PRE-ECLAMPSIA AND ECLAMPSIA (Table 2) 1. Central nervous system (CNS) (a) Cerebral irritation and convulsions In severe pre-eclampsia and eclampsia, there is an increased CNS irritability (headache, visual disturbances, hyperreflexia, convulsions). The occurrence of convulsions is not related to an elevation in blood pressure as compared to hypertensive encephalopathy (40% seizures are post natal, 38% seizures are antepartum, 18% seizures are intrapartum). Also, retinal changes are less common in preeclampsia and eclampsia as compared to hypertensive encephalopathy. Some of the etiologic mechanisms that are implicated in the pathogenesis of eclamptic convulsions have included cerebral vasoconstriction or vasospasm hypertensive encephalopathy, cerebral edema or infarction, cerebral haemorrhage, and metabolic encephalopathy. However, it is not clear whether these findings are causes or an effect of the convulsions. Prophylaxis for convulsions should be started with signs of cerebral irritability such as headache, visual disturbances, epigastric pain or hyperreflexia. Following a single eclamptic convulsion, prophylaxis with magnesium sulphate should always be instituted, unless there are major contraindications. Conclusions may occur at moderately elevated blood pressures and blood pressure alone is a poor predictor of the likelihood of occurrence of a convulsion. Although phenytoin was widely used in past for the prevention and control of eclamptic convulsions, recent evidence no longer supports its use. Table 2: Pathophysiology of PIH. CNS
Ischemic foci; CVA; ICP may be raised
CVS
Vasospasm; hypertension; poor perfusion;diastolic dysfunction
Respiratory
V/Q imbalance; airway oedema (pulmonary and laryngeal)
Renal
Protenuria; renal failure
GIT
Periportal necrosis; oedema; reduced metabolism
Coagulation
Low platelets; DIC
Haemodynamics
Raised PCV; low blood volume
Feto-placental Unit
Reduced IUBF; IUGR; abruptio placenta
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The first priority in the management of eclampsia is to prevent maternal injury and to support respiratory and cardiovascular functions. During or immediately after the acute convulsive episode, supportive care should be given to prevent serious maternal injury and aspiration, assess and establish airway potency, and insure maternal oxygenation. During this time, the bed’s side rails should be elevated and padded, a padded tongue blade is inserted between the teeth (avoid inducing gag reflex), and physical restraints may be needed[15]. To minimize the risk of aspiration, the patient should lie in lateral decubitus position, and vomitus and oral secretion are suctioned as needed. Left lateral position is used while transporting and nursing an unconscious patient to avoid airway obstruction and aspiration. If the airway reflexes are diminished, then the patient may need endotracheal intubation for airway protection. During the convulsive episode, hypoventilation and respiratory acidosis often occur. Although the initial seizure lasts only a few minutes, it is important to maintain oxygenation by supplemental oxygen administration via a face-mask with or without oxygen reservoir at 8-10 L/min [15]. After the convulsion has ceased, the patient begins to breathe again and oxygenation is rarely a problem. However, maternal hypoxemia and acidosis may develop in women who have had repetitive convulsions and in those with aspiration pneumonia, pulmonary edema, or a combination of these factors. Transcutaneous pulse oximetry to monitor oxygenation should be used in all eclamptic patients. Arterial blood gas analysis is required if the pulse oximetry results are abnormal (oxygen saturation at or below 92%). The next step in the management of eclampsia is to prevent recurrent convulsions. Magnesium sulphate (MgSO4) IV is preferred for controlling convulsions. It is used as an anticonvulsant in eclampsia due to a generalized depression of the nervous system. Magnesium sulphate does not seem to be an anticonvulsant but is known to be a potent cerebral vasodilator. It is thought to reverse cerebral vasoconstriction by blocking calcium influx through the NMDA (N-methyl-D-aspartate) subtype of the glutamate channel. Magnesium sulphate increases the uteroplacental blood flow and behaves as a mild tocolytic agent. It has a number of side effects which includes flushing, reddening of the face and respiratory depression. The loading dose is 4 g (IM) plus 5 g in each buttock. For an IV loading dose it is administered 4-6 g IV. The maintenance dose is 5 g IM every four hourly and 1-2 g/hr infusion respectively. Approximately 10% of eclamptic women will have a second convulsion after receiving MgSO4. In these women, another bolus of 2 g magnesium sulfate can be given intravenously over 3-5 minutes A magnesium level of
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4-6 mmol/L causes nausea, vomiting, somnolence, double vision, slurred speech, and loss of patellar reflex. A rise to 6.5-7.5 mmol/L can cause muscle paralysis and respiratory arrest. If it rises above 10 mmol/L then there is a high chance of a cardiac arrest. A serum magnesium level of more than 5 mmol/L is a warning (physiological level: 0.75-1.1 mmol/L, therpeutic 2-4 mmol/L). Some points to be kept in mind are (a) Hourly measurement of patellar reflex, respiratory rate and volume are carried out to avoid toxicity. If deep tendon reflexes are absent, withhold MgSO4 until reflexes return. (b) Significant respiratory depression is treated with calcium gluconate 1 g IV over 10 minutes. (c) Monitoring of Mg level to be considered in patients with oliguria (urine output <100 mL/4 hr). Therapeutic Mg range is 2-4 mmol/L. If serum levels are not available the maintenance dose should be reduced to 0.5 g/hr. (d)If seizure continue despite MgSO4, use diazepam or thiopentone infusion. Thiopental is preferred in the prepartum period since large doses of diazepam may be associated with neonatal hypotonia and impaired thermoregulation Intravenous solutions of diazepam also contain sodium benzoate, which may compete with bilirubin for binding sites on albumin. This is particularly hazardous for the preterm neonate in whom diazepam administration may precipitate kernicterus. (e) Intubation may become necessary in order to protect airway and ensure adequate oxygenation. Further seizures should be managed by IPPV and muscle relaxation. (f ) The next step in the management of eclampsia is to reduce the blood pressure to a safe range but at the same time avoid significant hypotension. The objective of treating severe hypertension is to avoid loss of cerebral autoregulation and to prevent congestive heart failure without compromising cerebral perfusion or jeopardizing uteroplacental blood flow that is already reduced in many women with eclampsia. (g) Parenteral MgSO4 should be continued for at least 24 hours after delivery and/or for at least 24 hours after the last convulsion[16]. Choice of anticonvulsant[17,18] The Collaborative Eclampsia Trial [16] was an international multicentre randomised trial involving 1680 women with eclampsia. The trial was divided into two arms. The first compared magnesium sulphate with diazepam and the second compared magnesium sulphate with phenytoin in the prevention of recurrent seizures. Maternal and
neonatal morbidity and mortality were the outcome measures. This study concluded that magnesium sulphate should be the drug of choice for eclampsia. Phenytoin appeared to cause more maternal and neonatal morbidity and diazepam and phenytoin were associated with increased recurrence of seizures compared with magnesium sulphate. (b) Cerebrovascular accidents Patients having convulsion and unconsciousness may have a spectrum of intracranial changes e.g., petichial haemorrhages, white matter oedema, intraventricular haemorrhage. Studies in these patients with MRI has shown lesions most common in the distribution of posterior cerebral artery and are associated with visual disturbances. Lesions in the basal ganglia and deep white matter are less common and are associated with mental changes. Intaventricular haemorrhages are the most severe form leading to prolonged unconsciousness. Cerebral imaging (MRI & CT) is not indicated in eclampsia. However, imaging is necessary to exclude haemorrhage and other serious abnormalities in women with focal neurological deficits or prolonged coma[19]. (c) Raised intracranial pressure Some patients may have a raised intracranial pressure and this may be managed on standard guidelines: (a) elevated head 30º, (b) mannitol, (c) IPPV with normocarbia or mild hypocarbia (hyperventilation) with PCO2 not less than 25 mmHg. (d) Prolonged unconsciousness An unconscious patient needs nursing care to protect eyes, pressure points, feeding etc. Monitoring of the level of unconsciousness may be done with Glasgow coma scale. 2. Cardiovascular system The haemodynamic changes of pre-eclampsia can be described as hypertension, increased systemic vascular resistance, decreased intravascular volume and decreased cardiac output. Pulmonary edema may occur because of iatrogenic fluid overload, decreased left ventricular function, increased capillary permeability and narrowing of the colloid osmotic-pulmonary capillary wedge pressure gradient. This is more likely to occur after delivery, particularly in patients who are older or multiparous or have preexisting hypertension. Haemodynamic monitoring and assessment Blood pressure measurement: The cuff size used for the measurement of blood pressure has to be appropriate as this could lead to fallacies in the diagnosis. The cuff has to be appropriate to the arm circumference. A regular cuff size
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(12 × 23 cm) is used if the arm circumference is less than 33cms. A larger cuff (15 × 33 cm) is used if the arm circumference is 33-41 cm and a thigh cuff (18 × 36 cm) must be used if the arm circumference is greater than 41 cm. The sphyngomanometer and the heart must be at the same level while measuring the blood pressure. Korotokoff 4 sounds may be better in defining the level of diastolic pressure[20].
increased sensitivity to circulating adrenaline, noradrenaline and angiotensin II. In addition to the low plasma volume, the plasma albumin is also reduced as a result of loss in urine and loss across leaky capillaries leading to a reduced colloid osmotic pressure. A normal colloid osmotic pressure is 22 mmHg in normotensive patients at term. The colloid osmotic pressure in moderate to severe preeclampsia drops to 15-20 mmHg.
Invasive blood pressure monitoring should be used while administering intravenous antihypertensive agents.
Control of hypertension
Central venous pressure monitoring Controversy exists as to whether central venous pressure monitoring is helpful, as it may not accurately reflect pulmonary capillary wedge pressure. Most cases are managed without such monitoring. One study, using invasive monitoring in 49 patients with severe preeclampsia, demonstrated normal or high cardiac output in the presence of normal wedge and central venous pressure, and inappropriately high systemic vascular resistance [20]. It concluded, that because filling pressures were normal, fluid should be given cautiously to avoid precipitating pulmonary oedema. In patients with severe pre-eclampsia or eclampsia, induction of anaesthesia or starting a labour epidural can be done after the CVP is brought to a level of 6-7 cm of water. This would avoid precipitous falls in blood pressure. When an internal jugular or a subclavian cannulation is planned, one has to keep the coagulation disorders these patients could have in mind and it has to be performed by an experienced person. It may be preferable to insert central venous catheter via a peripheral site such as the antecubital fossa. Pulmonary artery catheterization The central haemodynamic changes occurring in patients with severe pre-eclampsia or eclampsia have been studied by Mabie, et al and in these patients there is a generalized arterial vasospasm with a 30-40% decrease in blood volume[21]. Systemic vascular resistance (SVR) is increased with increased left ventricular stroke work index (LVSWI) leading to left ventricular strain due to chronic hypertension. There is also a low pulmonary capillary wedge pressure (PCWP). Consequently there may be a left ventricular diastolic dysfunction with poor correlation between CVP and PCWP. Measurement/monitoring of these parameters needs a pulmonary artery catheter (SwanGanz) in pulmonary oedema, intractable HTN, refractory oliguria, haemorrhagic hypovolaemia requiring massive fluid resusctitation. Catheter as only a central venous pressure monitoring may be unreliable guide for fluid replacement in a small percentage of cases. There is an Apollo Medicine, Vol. 3, No. 1, March 2006
Aim is to keep mean arterial pressure between 100-140 mmHg (130/90-170/110 mmHg) to maintain adequate placental blood flow. Management includes: (a) Bed rest with avoidance of aortocaval compression may be all that is required. (b) Vasodilation should be preceded by intravascular expansion to avoid fall in blood pressure. (c) Pain management using epidural catheter may be used if there is no coagulopathy. (d) Antihypertensive drug therapy: It is preferable to use invasive blood pressure monitoring when intravenous antihypertensive drugs are used. Hydralazine: This is the first line drug if available. Administered as increments of 5 mg titrated against blood pressure. Onset is seen in 15 minutes. Therefore 15-20 minutes intervals should be allowed between increments or severe hypotension may occur. Hypotension and tachycardia generally respond to fluids. Hydralazine crosses the placenta and can cause neonatal hypotension. Hydralazine has been seen to produce fetal tachycardia with late decelerations. Neonatal thrombocytopenia has also been reported in association with the use of hydralazine. Needs fetal monitoring. Its duration of action is six to eight hours. Side effects include hypotension, tachycardia, tremor, headache, nausea, and vomiting. Unfortunately, this may mimic impending eclampsia. Nifedipine: Principal use has been in acute management of very high blood pressures with 5-10 mg (orally) being the usual dose and can be repeated after 30 minutes. This drug may be administered orally or sublingually. This can be used in graded doses sublingually to achieve the necessary clinical effect. Rebound hypotension could be a problem if the dose is excessive. It has also been seen to exacerbate the effect of MgSO4. Methyldopa: Reserved for patients with an element of chronicity to their hypertension. Labetelol: One mg/kg of labetelol blocks response to endotracheal intubation without neonatal effects. The drug may be administered in progressively increasing doses (20, 40, 80 mg) every 10-15 minutes to a maximum dose of
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300 mg. This may cause fetal bradycardia, hypotension, and hypoglycemia. Fear of the effects of betablockade on the fetus makes the use of other betablocking drugs in the high risk pregnancies unadvisable. Needs fetal monitoring. This is contraindicated in patients with history of asthma and first degree heart block. This drug improves uteroplacental perfusion, decreases uterine vascular resistance. Sodium Nitroprusside: This drug has limited use due to fear of cyanide toxicity in the fetus. There are also doubts as to its safety in the presence of raised intracranial pressure such as may occur in a patient who has had several convulsions. Nitroglycerine: Acts on venous capacitance vessels. Does not prevent response to intubation. Patients receiving volume expansion are markedly resistant. Initial intravenous infusion rate is 5 mg/min and titrated to desired response by doubling the dose every 5 minutes. Side effects include tachycardia, nausea, vomiting, pallor, sweating, headache and methaemoglobinaemia. Once delivery has occurred, other oral antihypertensive agents such as labetalol or nifedipine can be used to keep systolic blood pressure below 155 mm Hg and diastolic blood pressure below 105 mm Hg. The recommended dose of oral labetalol is 200 mg every 8 hours (maximum dose of 2,400 mg/d), and the recommended dose of nifedipine is 10 mg orally every 6 hours (maximum dose of 120 mg/d). We would prefer oral nifedipine because it offers the benefit of improved diuresis in the postpartum period[16]. Fluid management Fluid management is a challenge in severe preeclamptics and eclamptics complicated by decreased urine output, poor CVP-PCWP correlation, and wide variability of haemodynamic profile. In severe pre-eclamptics and eclamptics, low plasma oncotic pressure and left ventricular dysfunction can combine to produce high incidence of pulmonary oedema and cerebral oedema. Diuretics and the administration of high concentrations of colloid solutions (albumin, hetastarch) should not be used to decrease peripheral edema caused by further depletion of intravascular volume and an increased risk of pulmonary edema and uteroplacental insufficiency. Severe preeclamptics poorly tolerate overhydration (preloading) before regional anaesthesia if ventricular dysfunction is present. They are also sensitive to sympathetic blockade as a result of regional anaesthesia due to decreased blood volume. However, 400-500 colloid preloading prior to regional anaesthesia may reduce the risk of hypotension and fetal distress. 3. Hepatic In hepatic disorders raised enzymes may occur due to
periportal or focal necrosis with large hyaline deposits of fibrin-like material in sinusoids. Decreased synthesis of pseudo cholinesterase may prolong suxamethonium, chloroprocaine or tetracaine. Hyperbilirubinemia, however, is not a common feature. Hepatic dysfunction may form part of the HELLP syndrome, which complicates 0.3% of all pregnancies and up to 20% of women with severe pre-eclampsia. The syndrome comprises haemolysis, increased liver enzymes, and low platelets with epigastric or right upper quadrant pain. Thrombocytopenia (platelets <100,000/mL) and also qualitative platelet dysfunction can occur[20,22,23]. Subcapsular hematoma of the liver can cause intense epigastric pain and, rarely, the liver may rupture. Disseminated intravascular coagulation occurs in 7% of patients with eclampsia but the cause is unclear[23]. More than 50% patients may need blood or blood products if they develop HELLP syndrome. Massive transfusion may be required in some case of HELLP syndrome. These patients may manifest a number of problems associated with massive transfusion. In cases where patients have a coagulopathy, regional anaesthesia is contraindicated. Deferential diagnosis is preeclampsia versus acute fatty liver of pregnancy, viral hepatitis and other hepatic disorders. Assessments and management of the woman diagnosed with HELLP syndrome are the same as for the woman with severe preeclampsia. 4. Renal Glomerular involvement, probably due to a vascular basis of the disease leads to proteinuria. Examination shows subendothelial deposits, electron dense droplets in the glomerular epithelial cells that contain albumin, immunoglobolin, fibrinogen and complement. Oligouria is common due to hypoproteinaemia and decreased renal blood flow rather than a primary renal pathology[24]. This may be due to prerenal cause and may be distinguished from other causes by giving a fluid challenge. But one has to avoid giving repetitive, unmonitored fluid challenges. Dopamine may be started in a low dose 2-3 mcg/kg/min to improve renal perfusion. Progression to acute renal failure is common especially with hypertension and HELLP syndrome. Renal outcomes are usually good. 5. Pulmonary Respiratory assessments are performed to identify signs of pulmonary oedema, respiratory compromise, or magnesium toxicity. Respiratory rate is evaluated for rate quality and pattern, especially if receiving MgSO4, to identify early signs of toxicity. Laboured respiration or use of the accessory muscles is assessed; pulmonary oedema can develop very quickly. Tachypnoea and tachycardia are early signs of evolving pulmonary oedema. Skin color and mucous membranes are assessed for the presence of
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cyanosis, which may indicate problems with oxygenation. Oxygenation status is assessed with pulse oximetry. However, pulse oximetry should not replace clinical assessments. During active convulsion, maternal injury should be avoided. Since the woman may have vomiting, the airway must be protected. Maintain adequate oxygenation. Once the convulsion has stopped and the patient has begun spontaneous respirations, oxygenation status is monitored. If spontaneous respirations are not present, ventilatory support will be required. Minimize the risk of aspiration. The woman should be positioned to facilitate drainage from the mouth. Suction equipment should be readily available and in working order. Also, if supplemental oxygen is being administered by facemask, be aware of the possibility of vomiting and aspiration. Correct maternal acidaemia. Blood gas analysis will allow monitoring oxygenation and pH status. Respiratory acidaemia is possible after convulsion, but sodium bicarbonate is not administered unless the pH is less than 7.10[12]. Ensuring adequate respiratory status is essential. Since all anticonvulsant drugs are respiratory depressants and may interact with each other, polypharmacy should be avoided. Respiratory failure is diagnosed clinically and by blood gas analysis. A fall in PaO2 to less than 60 mmHg or/and a rise in PCO2 to more than 45 mmHg would need mechanical support. Airway is protected with a cuffed endotracheal tube. Ventilation is also required temporarily after emergency lower segment caesarean section or in uncontrollable convulsive states. Once the delivery has occurred the blood gas analysis is satisfactory and convulsions are controlled, and other systems are in an acceptable condition, a decision to wean off is taken. Patient is weaned from the ventilator and is put on T-piece trial. Once the reflexes have returned Table 3: Indications of immediate delivery. 1. Non-reassuring fetal status 2. Vaginal bleeding
and the patient is conscious and oriented (after withdrawal of sedation) and able to breathe around the tube, the trachea is extubated. MANAGING THE NEONATE Ultimate goal of any protocol for management of preeclampsia must be maternal safety first followed by delivery of a live, mature (if possible) newborn in optimal condition (Table 3)[25-28]. Essentially two management options are available: • •
Immediate delivery for maternal benefit and subsequent neonatal intensive care. Pregnancy prolongation (expectant management or 4 hour delay with corticosteroid therapy for maturation of lungs). The study by Witlin, et al has the following results[29].
1. No correlation between severity of maternal disease and fetal outcome. 2. No correlation between fetal variables (5 min APGAR, cord pH, PDA, O2 requirements, necrotizing enterocolitis) and fetal outcome. 3. Incidence of RDS (respiratory distress syndrome) is inversely proportional to gestational age. 4. Expectant management and steroid use did not decrease RDS. 5. Incidence of RDS is directly proportional to cesarean delivery (incidence of cesarean decreased with increased gestation). 6. Birth weight was the most important determinant of survival (IUGR decreased survival). 7. Any delivery after 34 weeks is safe as the lung is mature after this period. LABOUR ANALGESIA Mild to moderate preeclampsia may be allowed to proceed with normal labour. Epidural block may be instituted early if the coagulation parameters are normal. This may be useful in controlling stress and pain. It is also thought that an epidural block may improve the placental intervillous blood flow.
3. Uncontrolled severe hypertension
ANAESTHETIC CONSIDERATIONS
4. Pulmonary oedema
1. Airway assessment to predict a difficult mask ventilation or intubation is a must. Mallampatti scoring must be done prior to anaesthesia. Post convulsion laceration of the tongue or mucosa may be predictive of a difficult ventilation or intubation. Presence of a stridor or excessive facial oedema may be predictive of airway oedema. In these patients it is important to take care that the endotracheal tube used is smaller than usual and
5. Persistent severe headache or visual changes 6. Compromised renal function 7. Platelet count of <100,000/mm3 or raised liver enzymes (AST/ALT) 8. Uncontrolled seizures 9. Attainment of 34 weeks of gestation
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extreme care is taken to avoid trauma during intubation. However, in many of these patients it is not possible to predict all the problems and there may be an unanticipated difficult airway so the anaesthesiologist must be ready with the equipment needed in this situation (introducers, bougie, laryngeal masks, surgical airway, fiberoptic bronchoscopes etc.). Awake intubation may be necessary in predicted difficult airway but nasotracheal intubation requires a normal coagulation status. 2. A rapid sequence induction is carried out and general anaesthesia is preceded with a 3-minute preoxygenation. Theopentone 4-5 mg/kg or etomidate 0.2 mg/kg with suxamethonium (1-1.5 mg/kg) with Sellick’s maneuver should be used for achieving rapid airway access. 3. Haemodynamic response to intubation can cause a dangerous rise in blood pressure and drugs to control this may have to be used in some cases. Lignocaine, betablockers, opioids, nitroglycerine and sodium nitroprusside have been seen to affect the fetus. Newer narcotics such as alfentanil when administered prior to suxamethonium can decrease the haemodynamic response to intubation and has a short duration of action in the fetus. 4. When MgSO4 or nifedepine has been administered to the patient there may be an interaction with the nondepolarising muscle relaxant in causing a prolonged block. Neuromuscular monitoring is preferable in these cases. 5. Regional anaesthesia is contraindicted in patients with abnormal coagulation parameters, patients with a history of convulsions or unconsciousness. The other contraindications to regional anaesthesia also apply in these situations. The patients must be well hydrated prior to anaesthesia as there could be precipitous fall in blood pressure. Newer techniques like the combined spinal epidural are preferable to a single dose spinal as there is a better control over the haemodynamics.
maternal or fetal complications were attributable to any method if steps are taken to ensure careful approach to the method used. 2. Vasopressor and fluid requirements are more with regional anaesthesia. Delivery is the ultimate care for the maternal disease. However, maternal benefits must be weighed against the neonatal risks of preterm delivery. Delivery of infants less than 24 weeks gestation with immature fetal pulmonary profiles result in intensive and prolonged neonatal care associated with significant neonatal mortality and morbidity. CONCLUSION Eclampsia is the commonest obstetritic condition requiring ICU admission in the developing countries. Women diagnosed with the HELLP syndrome or eclampsia present a variety of management issues and problems for the health care provider. Regardless of the diagnosis, severe pre-eclampsia, the HELLP syndrome, or eclampsia can profoundly affect the woman and her fetus. The underlying pathophysiology must be evaluated and treated with both patients in mind at all times. Nurses caring for the woman diagnosed with severe preeclampsia, the HELLP syndrome, and eclampsia must be fully aware of the risk factors, diagnostic criteria, appropriate management regimes, and the potential complications for both the woman and her fetus. The Collaborative Eclampsia Trial has shown that magnesium sulphate is the drug of choice for routine anticonvulsant management of women with eclampsia; a similar study is warranted to establish the antihypertensive drug of choice. REFERENCES
6. Depending on the preoperative problems and the conditions of the patient, postoperative ventilation and supportive intensive care are continued in the postoperative period. All patients with severe preeclampsia need intensive care for 24-48 hours in the postoperative period. The same standard of care must be continued. One must remember that convulsions can occur upto 7 days in the postoperative period.
1. Poole J. Legal and professional issues in critical care obstetrics. Crit Care Nurs Clin North Am 1992; 4: 687-690. 2. Sibai B. Hypertension in pregnancy. In: Gabbe S, Niebyl J, Simpson J, eds. Obstetrics: Normal & Problem Pregnancies. 3rd ed. New York: Churchill Livingstone; 1996: 935-996. 3. Makhseed M, Musini VM. Eclampsia in Kuwait 1981-1993. Aust N Z J Obstet Gynaecol 1996; 36: 258-263. 4. Sibai BM. Eclampsia. VI. Maternal-perinatal outcome in 254 consecutive cases. Am J Obstet Gynaecol 1990; 163:1049-1055. 5. Lubarsky SL, Barton JR, Friedman SA, Nasreddine S, Ramaddan MK, Sibai BM. Late postpartum eclampsia revisited. Obstet Gynaecol 1994; 83: 502-505.
In a randomized study by Wallace, et al three groups of 27 patients received GA, epidural or Combined spinal epidural[22].
6. Wilcox L, Marks J. From Data to Action: CDC’s Public Health Surveillance for Women, Infants, and Children. Washington, DC,: US Department of Health & Human Services, Public Health Services, Centres for Disease Control and Prevention; 1994: 412.
1. All methods are equally acceptable and no serious
7. American College of Obstetricians and Gynaecologists.
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8. Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. Br J Obstet Gynaecol 1992; 99: 547-553.
20. Mushambi MC, Halligan AW, Williamson K. Recent development in the pathophysiology and management of pre-eclampsia. Br J Anaesth 1996; 133-148.
9. Douglas KA, Redman CWG. Eclampsia in the United Kingdom. BMJ 1994; 309:1395-1400.
21. Mabie WC, Ratts, Sibai BM. The Central Haemodynamics of Severe Pre-eclampsia. Am J Obstet Gynaecol 1989; 161: 1443-1448.
10. Saftlas AF, Olson DR, Franks AL, et al. Epidemiology of pre-eclampsia and eclampsia in the United States, 19791986. Am J Obstet Gynaecol 1990; 163: 460-465.
22. Poole JH. HELLP Syndrome and coagulopathies of pregnancy. Clin North Am 1993; 5: 475-487.
11. Anand LPN, Bukshee K. Maternal mortality in a referral hospital of northern India-A 16 years review. J Fam Welfare 1997; 43, 3.
23. Leduc L, Wheeler JM, Krishon B, Cotton DB. Coagulation profile in severe pre-eclampsia. Obstet Gynaecol 1992; 79: 14-18.
12. Sengupta A, Murlidhar V, Bhattacharya A, Gode AG. Intensive care management of severe eclamptic patientsAn overview. XIX International Congress on Pathophysiology of Pregnancy. Jamshedpur; 1987.
24. Clark SL, Greenspoon JS, Aldhal D, Phelan JP. Severe pre-eclampsia with persistent oliguria: management of haemodynamic subsets. Am J Obset Gynaecol 1986; 154: 490-94.
13. Mattar F, Sibai BM. Eclampsia. VIII. Risk factors for maternal morbidity. Am J Obstet Gynaecol 2000; 182: 307-312
25. Friedman SA, Schiff SA, Kao L, Sibai BM. Neonatal outcome after preterm delivery for preeclampsia. Am J Obstet Gynaecol 1993; 169: 1096-101.
14. Nisell H, Palm K, Wolff K. Prediction of Maternal and Fetal Complications in Preeclampsia. Acta Obstetricia et Gynecologica Scandinavica 2000; 79: 19-23.
26. Chari RS, Friedman SA, Schiff E, Frangich AT, Sibai BM. Is fetal neurologic and physical development accelerated in pre-eclampsia? Am J Obstet Gynaecol 1996; 174 829832.
15. Sibai BM. Hypertension. In: Gabbe SG, Niebyl JR, Simpson JL, editors. Obstetrics: normal and problem pregnancies. 4th ed. New York (NY); Churchill Livingstone; 2002; p. 945-1004.
27. Schiff E, Friedman SA, Sibai BM. Conservative management of severe pre-eclampsia remote from term. Obstet Gynaecol 1994; 84: 626-630.
16. Baha M. Sibai. Diagnosis, Prevention, and Management of Eclampsia Obstetrics & Gynaecology 2005; 105: 402-410.
28. Tubman TRJ, Rollins MD, Halliday HL. Increased incidence of respiratory distress syndrome in babies of hypertensive mothers. Arch Dis Child 1991; 66:52-54.
17. Dudley L. Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia: Evidence from the collaborative eclampsia trial. Lancet 1995; 345:14551463. 18. Repke JT, Friedman SA, Kaplan PW. Prophylaxis of eclamptic seizures: Current controversies. Clin Obstet Gynaecol 1992; 35:365-74 19. Dahmus MA, Barton JR, Sibai BM. Cerebral imaging in eclampsia: magnetic resonance imaging versus
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29. Saade GR, Mattar F, Sibai BM. Predictors of neonatal outcome in women with severe preeclampsia or eclampsia between 24 and 33 weeks gestation. Am J Obstet Gynaecol 2000; 607-611. 30. Wallace DH, Leveno KJ, Cunningham B, Giesecke AH, Shearer V, Sidwai JE. Randomised Comparison of General and Regional Anaesthesia for Cesarean Delivery in Pregnancies Complicated by Severe Preeclampsia. Obstet Gynaecol 1995; 86: 193-199.
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INTENSIVE CARE MANAGEMENT OF SEVERE PRE-ECLAMPSIA AND ECLAMPSIA V. Murlidhar* and Sameer Bolia** Senior Consultant*, Senior Resident**, Department of Anaesthesia, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. Correspondence to: Dr. V. Murlidhar, Senior Consultant, Department of Anaesthesia, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. Pregnancy induced hypertension is a common medical complication of pregnancy and is a significant contribution to maternal and perinatal morbidity and mortality. Early diagnosis, increased patient awareness and appropriate medical intervention, especially intensive care management of severe preeclampsia and eclampsia have led to marked fall in mortality in this group of patients. In this review article, the pathophysiology, effect on different organ systems, choice of drugs (anticonvulsants and antihpertensives), support of a critically ill patient in the intensive care, monitoring, anaesthetic considerations and management of the neonate are discussed. Key words: Intensive care, Pre-eclampsia, Eclampsia, Pregnancy induced hypertension, anticonvulsants, HELLP syndrome, Convulsions.
INTRODUCTION HYPERTENSIVE disorders are the most common medical complication of pregnancy[1,2]. Two basic types of hypertension occur during pregnancy: chronic hypertension and pregnancy-induced hypertension (PIH). Chronic hypertension is that which predates pregnancy or continues beyond 42 weeks postpartum. Pregnancy-induced hypertension generally occurs after 20 weeks of pregnancy. Clinically chronic hypertension and pregnancy-induced hypertension (PIH) may coexist. Further, PIH is classified according to the maternal organ systems affected. Preeclampsia is the progression of PIH and is classified as severe or mild based on maternal and fetal clinical findings (Table 1). Eclampsia is defined as the development of convulsions and/or unexplained coma during pregnancy or postpartum in patients with signs and symptoms of pre-eclampsia. In the western world, the reported incidence of eclampsia ranges from 1 in 2,000 to 1 in 3,448 pregnancies. The reported incidence is usually higher in tertiary referral centres, in multifetal gestation, and in populations with no prenatal care[3,4]. Current definitions place less reliance on the presence of pre-eclampsia as eclampsia can develop without preceding symptoms or signs in up to 38% of cases.extra. Late postpartum eclampsia is defined as eclampsia that occurs more than 48 hours, but less than 4 weeks, after delivery[5]. The cause is a pregnancy specific, underlying multiorgan disorder involving vascular endothelial damage, intravascular coagulation, and vasoconstriction leading to Apollo Medicine, Vol. 3, No. 1, March 2006
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end organ ischaemia. There may be a variety of presentations and classic features are not always present. Changes have occurred in the recommended treatment for eclamptic seizures and are considerably different from other seizure disorders (including management of hypertension and careful fluid balance). INCIDENCE, MORTALITY AND MORBIDITY A significant contributor to maternal and perinatal morbidity and mortality[6,7], hypertension is estimated to complicate approximately 7-10% of all pregnancies[8]. In the developing and underdeveloped world, the incidences are thought to be 20 times more than in the developed world. Eclampsia is responsible for approximately 50,000 maternal deaths worldwide each year. A prospective descriptive survey of every case of eclampsia in the UK was carried out in 1992[9]. Two hundred and seventy nine consultant led obstetric units were surveyed. Five hundred and eighty two possible cases were reported and 383 were subsequently confirmed as cases of eclampsia. This gave a rate of 4.9 per 10 000 maternities. This incidence is similar to that reported in the USA in 1983-1986 of 4.3 per 10 000 [10]. Sixty eight per cent of seizures occurred in hospital; 44% were postpartum; 18% were intrapartum. The remainder were antepartum. A recent study at the All India Institute of Medical Sciences (AIIMS) shows the incidence of toxaemia including eclampsia to be 16.4% (1995-1997) in 46,443 admissions (116 maternal death)[11]. A study at
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Table 1: Features under mild and severe pre-eclampsia. Abnormality
Mild
Severe
Diastolic blood pressure
<100
>110 or higher
Proteinuria
Trace to 1+
Persistent 2+ or more
Headache
Absent
Present
Visual disturbances
Absent
Present
Upper abdominal pain
Absent
Present
Oliguria
Absent
Present
Convulsions
Absent
Present (eclampsia)
Sr. creatinine
Normal
Elevated
Thrombocytopenia
Absent
Present
Liver enzymes elevation
Minimal
Marked
Fetal growth restriction
Absent
Obvious
Pulmonary edema
Absent
Present
Safdarjung Hospital (1975-84) studied the various causes of maternal mortality and morbidity between 1975 to 1984 and came up with the following facts: (a) Mortality rate of eclampsia was 7.05/1000 births (197584); (b) Rising eclampsia mortality from 10.2% (1975) to 15.02% (1984). Managing them in an intensive care unit (1984-86) led to a marked fall in mortality [12]. This is supported by a number of studies and it is mandatory to manage severe pre-eclampsia and eclampsia in the ICU. Eclampsia and pre-eclampsia continue to be responsible for very high morbidity and mortality in the developing world due to inadequate antenatal care, absence of a referral network and management in ill-equipped centres. Pregnancies complicated by eclampsia are also associated with increased rates of maternal morbidities [13], such as abruptio placentae (7-10%), disseminated intravascular coagulopathy (7-11%), pulmonary edema (3-5%), acute renal failure (5-9%), aspiration pneumonia (2-3%), and cardiopulmonary arrest (2-5%). Adult respiratory distress syndrome and intracerebral haemorrhage are rare complications among eclamptic series reported from the developed world. The risks of diffuse intravascular coagulation (8%); haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (10-15%); and liver haematoma (1%) are similar in eclamptic and severely preeclamptic patients. It is important to note that maternal complications are significantly higher among women who develop antepartum eclampsia, particularly among those who develop eclampsia remote from term.
OBJECTIVES OF INTENSIVE CARE MANAGEMENT 1. Organ support and management of multiorgan failure 2. Prevention and management of the critical incidents such as airway obstruction, aspiration etc. 3. Medical and obstetric management of a potentially reversible and manageable state 4. Neonatal management The understanding of the disease has changed considerably in the last two decades. It was realized that early shifting of these patients to an intensive care unit led to a drastic fall in the mortality and morbidity. The question arises at what point of time these patients should be shifted to an intensive care unit. Sengupta, et al[12] were using the criteria of (a) severe hypertension, (b) prolonged unconsciousness, (c) multiple convulsions, (d) respiratory distress and respiratory failure. But these criteria have expanded with the understanding of the disease and have grown to include hepatic and renal problems. Even signs of cerebral irritation should be considered a warning sign and necessitate close monitoring. The individual predictive value of these risk factors for risk identification has been questioned. In a recent study Nisell, et al have identified factors predicting maternal and fetal complications[14]. The only factor, which they found to be of predictive value, was diastolic blood pressure. Severe pre-eclampsia and eclampsia need to be referred and managed in a well-equipped center. The center should have facilities to diagnose and define the disease and its complications. It should have facilities to intensively manage various problems, e.g., ICU with facilities for
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management of the critically ill patients, operation theatre, a well-equipped blood bank and neonatal intensive care. PATHOPHYSIOLOGICAL BASIS OF CRITICAL CARE IN SEVERE PRE-ECLAMPSIA AND ECLAMPSIA (Table 2) 1. Central nervous system (CNS) (a) Cerebral irritation and convulsions In severe pre-eclampsia and eclampsia, there is an increased CNS irritability (headache, visual disturbances, hyperreflexia, convulsions). The occurrence of convulsions is not related to an elevation in blood pressure as compared to hypertensive encephalopathy (40% seizures are post natal, 38% seizures are antepartum, 18% seizures are intrapartum). Also, retinal changes are less common in preeclampsia and eclampsia as compared to hypertensive encephalopathy. Some of the etiologic mechanisms that are implicated in the pathogenesis of eclamptic convulsions have included cerebral vasoconstriction or vasospasm hypertensive encephalopathy, cerebral edema or infarction, cerebral haemorrhage, and metabolic encephalopathy. However, it is not clear whether these findings are causes or an effect of the convulsions. Prophylaxis for convulsions should be started with signs of cerebral irritability such as headache, visual disturbances, epigastric pain or hyperreflexia. Following a single eclamptic convulsion, prophylaxis with magnesium sulphate should always be instituted, unless there are major contraindications. Conclusions may occur at moderately elevated blood pressures and blood pressure alone is a poor predictor of the likelihood of occurrence of a convulsion. Although phenytoin was widely used in past for the prevention and control of eclamptic convulsions, recent evidence no longer supports its use. Table 2: Pathophysiology of PIH. CNS
Ischemic foci; CVA; ICP may be raised
CVS
Vasospasm; hypertension; poor perfusion;diastolic dysfunction
Respiratory
V/Q imbalance; airway oedema (pulmonary and laryngeal)
Renal
Protenuria; renal failure
GIT
Periportal necrosis; oedema; reduced metabolism
Coagulation
Low platelets; DIC
Haemodynamics
Raised PCV; low blood volume
Feto-placental Unit
Reduced IUBF; IUGR; abruptio placenta
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The first priority in the management of eclampsia is to prevent maternal injury and to support respiratory and cardiovascular functions. During or immediately after the acute convulsive episode, supportive care should be given to prevent serious maternal injury and aspiration, assess and establish airway potency, and insure maternal oxygenation. During this time, the bed’s side rails should be elevated and padded, a padded tongue blade is inserted between the teeth (avoid inducing gag reflex), and physical restraints may be needed[15]. To minimize the risk of aspiration, the patient should lie in lateral decubitus position, and vomitus and oral secretion are suctioned as needed. Left lateral position is used while transporting and nursing an unconscious patient to avoid airway obstruction and aspiration. If the airway reflexes are diminished, then the patient may need endotracheal intubation for airway protection. During the convulsive episode, hypoventilation and respiratory acidosis often occur. Although the initial seizure lasts only a few minutes, it is important to maintain oxygenation by supplemental oxygen administration via a face-mask with or without oxygen reservoir at 8-10 L/min [15]. After the convulsion has ceased, the patient begins to breathe again and oxygenation is rarely a problem. However, maternal hypoxemia and acidosis may develop in women who have had repetitive convulsions and in those with aspiration pneumonia, pulmonary edema, or a combination of these factors. Transcutaneous pulse oximetry to monitor oxygenation should be used in all eclamptic patients. Arterial blood gas analysis is required if the pulse oximetry results are abnormal (oxygen saturation at or below 92%). The next step in the management of eclampsia is to prevent recurrent convulsions. Magnesium sulphate (MgSO4) IV is preferred for controlling convulsions. It is used as an anticonvulsant in eclampsia due to a generalized depression of the nervous system. Magnesium sulphate does not seem to be an anticonvulsant but is known to be a potent cerebral vasodilator. It is thought to reverse cerebral vasoconstriction by blocking calcium influx through the NMDA (N-methyl-D-aspartate) subtype of the glutamate channel. Magnesium sulphate increases the uteroplacental blood flow and behaves as a mild tocolytic agent. It has a number of side effects which includes flushing, reddening of the face and respiratory depression. The loading dose is 4 g (IM) plus 5 g in each buttock. For an IV loading dose it is administered 4-6 g IV. The maintenance dose is 5 g IM every four hourly and 1-2 g/hr infusion respectively. Approximately 10% of eclamptic women will have a second convulsion after receiving MgSO4. In these women, another bolus of 2 g magnesium sulfate can be given intravenously over 3-5 minutes A magnesium level of
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4-6 mmol/L causes nausea, vomiting, somnolence, double vision, slurred speech, and loss of patellar reflex. A rise to 6.5-7.5 mmol/L can cause muscle paralysis and respiratory arrest. If it rises above 10 mmol/L then there is a high chance of a cardiac arrest. A serum magnesium level of more than 5 mmol/L is a warning (physiological level: 0.75-1.1 mmol/L, therpeutic 2-4 mmol/L). Some points to be kept in mind are (a) Hourly measurement of patellar reflex, respiratory rate and volume are carried out to avoid toxicity. If deep tendon reflexes are absent, withhold MgSO4 until reflexes return. (b) Significant respiratory depression is treated with calcium gluconate 1 g IV over 10 minutes. (c) Monitoring of Mg level to be considered in patients with oliguria (urine output <100 mL/4 hr). Therapeutic Mg range is 2-4 mmol/L. If serum levels are not available the maintenance dose should be reduced to 0.5 g/hr. (d)If seizure continue despite MgSO4, use diazepam or thiopentone infusion. Thiopental is preferred in the prepartum period since large doses of diazepam may be associated with neonatal hypotonia and impaired thermoregulation Intravenous solutions of diazepam also contain sodium benzoate, which may compete with bilirubin for binding sites on albumin. This is particularly hazardous for the preterm neonate in whom diazepam administration may precipitate kernicterus. (e) Intubation may become necessary in order to protect airway and ensure adequate oxygenation. Further seizures should be managed by IPPV and muscle relaxation. (f ) The next step in the management of eclampsia is to reduce the blood pressure to a safe range but at the same time avoid significant hypotension. The objective of treating severe hypertension is to avoid loss of cerebral autoregulation and to prevent congestive heart failure without compromising cerebral perfusion or jeopardizing uteroplacental blood flow that is already reduced in many women with eclampsia. (g) Parenteral MgSO4 should be continued for at least 24 hours after delivery and/or for at least 24 hours after the last convulsion[16]. Choice of anticonvulsant[17,18] The Collaborative Eclampsia Trial [16] was an international multicentre randomised trial involving 1680 women with eclampsia. The trial was divided into two arms. The first compared magnesium sulphate with diazepam and the second compared magnesium sulphate with phenytoin in the prevention of recurrent seizures. Maternal and
neonatal morbidity and mortality were the outcome measures. This study concluded that magnesium sulphate should be the drug of choice for eclampsia. Phenytoin appeared to cause more maternal and neonatal morbidity and diazepam and phenytoin were associated with increased recurrence of seizures compared with magnesium sulphate. (b) Cerebrovascular accidents Patients having convulsion and unconsciousness may have a spectrum of intracranial changes e.g., petichial haemorrhages, white matter oedema, intraventricular haemorrhage. Studies in these patients with MRI has shown lesions most common in the distribution of posterior cerebral artery and are associated with visual disturbances. Lesions in the basal ganglia and deep white matter are less common and are associated with mental changes. Intaventricular haemorrhages are the most severe form leading to prolonged unconsciousness. Cerebral imaging (MRI & CT) is not indicated in eclampsia. However, imaging is necessary to exclude haemorrhage and other serious abnormalities in women with focal neurological deficits or prolonged coma[19]. (c) Raised intracranial pressure Some patients may have a raised intracranial pressure and this may be managed on standard guidelines: (a) elevated head 30º, (b) mannitol, (c) IPPV with normocarbia or mild hypocarbia (hyperventilation) with PCO2 not less than 25 mmHg. (d) Prolonged unconsciousness An unconscious patient needs nursing care to protect eyes, pressure points, feeding etc. Monitoring of the level of unconsciousness may be done with Glasgow coma scale. 2. Cardiovascular system The haemodynamic changes of pre-eclampsia can be described as hypertension, increased systemic vascular resistance, decreased intravascular volume and decreased cardiac output. Pulmonary edema may occur because of iatrogenic fluid overload, decreased left ventricular function, increased capillary permeability and narrowing of the colloid osmotic-pulmonary capillary wedge pressure gradient. This is more likely to occur after delivery, particularly in patients who are older or multiparous or have preexisting hypertension. Haemodynamic monitoring and assessment Blood pressure measurement: The cuff size used for the measurement of blood pressure has to be appropriate as this could lead to fallacies in the diagnosis. The cuff has to be appropriate to the arm circumference. A regular cuff size
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(12 × 23 cm) is used if the arm circumference is less than 33cms. A larger cuff (15 × 33 cm) is used if the arm circumference is 33-41 cm and a thigh cuff (18 × 36 cm) must be used if the arm circumference is greater than 41 cm. The sphyngomanometer and the heart must be at the same level while measuring the blood pressure. Korotokoff 4 sounds may be better in defining the level of diastolic pressure[20].
increased sensitivity to circulating adrenaline, noradrenaline and angiotensin II. In addition to the low plasma volume, the plasma albumin is also reduced as a result of loss in urine and loss across leaky capillaries leading to a reduced colloid osmotic pressure. A normal colloid osmotic pressure is 22 mmHg in normotensive patients at term. The colloid osmotic pressure in moderate to severe preeclampsia drops to 15-20 mmHg.
Invasive blood pressure monitoring should be used while administering intravenous antihypertensive agents.
Control of hypertension
Central venous pressure monitoring Controversy exists as to whether central venous pressure monitoring is helpful, as it may not accurately reflect pulmonary capillary wedge pressure. Most cases are managed without such monitoring. One study, using invasive monitoring in 49 patients with severe preeclampsia, demonstrated normal or high cardiac output in the presence of normal wedge and central venous pressure, and inappropriately high systemic vascular resistance [20]. It concluded, that because filling pressures were normal, fluid should be given cautiously to avoid precipitating pulmonary oedema. In patients with severe pre-eclampsia or eclampsia, induction of anaesthesia or starting a labour epidural can be done after the CVP is brought to a level of 6-7 cm of water. This would avoid precipitous falls in blood pressure. When an internal jugular or a subclavian cannulation is planned, one has to keep the coagulation disorders these patients could have in mind and it has to be performed by an experienced person. It may be preferable to insert central venous catheter via a peripheral site such as the antecubital fossa. Pulmonary artery catheterization The central haemodynamic changes occurring in patients with severe pre-eclampsia or eclampsia have been studied by Mabie, et al and in these patients there is a generalized arterial vasospasm with a 30-40% decrease in blood volume[21]. Systemic vascular resistance (SVR) is increased with increased left ventricular stroke work index (LVSWI) leading to left ventricular strain due to chronic hypertension. There is also a low pulmonary capillary wedge pressure (PCWP). Consequently there may be a left ventricular diastolic dysfunction with poor correlation between CVP and PCWP. Measurement/monitoring of these parameters needs a pulmonary artery catheter (SwanGanz) in pulmonary oedema, intractable HTN, refractory oliguria, haemorrhagic hypovolaemia requiring massive fluid resusctitation. Catheter as only a central venous pressure monitoring may be unreliable guide for fluid replacement in a small percentage of cases. There is an Apollo Medicine, Vol. 3, No. 1, March 2006
Aim is to keep mean arterial pressure between 100-140 mmHg (130/90-170/110 mmHg) to maintain adequate placental blood flow. Management includes: (a) Bed rest with avoidance of aortocaval compression may be all that is required. (b) Vasodilation should be preceded by intravascular expansion to avoid fall in blood pressure. (c) Pain management using epidural catheter may be used if there is no coagulopathy. (d) Antihypertensive drug therapy: It is preferable to use invasive blood pressure monitoring when intravenous antihypertensive drugs are used. Hydralazine: This is the first line drug if available. Administered as increments of 5 mg titrated against blood pressure. Onset is seen in 15 minutes. Therefore 15-20 minutes intervals should be allowed between increments or severe hypotension may occur. Hypotension and tachycardia generally respond to fluids. Hydralazine crosses the placenta and can cause neonatal hypotension. Hydralazine has been seen to produce fetal tachycardia with late decelerations. Neonatal thrombocytopenia has also been reported in association with the use of hydralazine. Needs fetal monitoring. Its duration of action is six to eight hours. Side effects include hypotension, tachycardia, tremor, headache, nausea, and vomiting. Unfortunately, this may mimic impending eclampsia. Nifedipine: Principal use has been in acute management of very high blood pressures with 5-10 mg (orally) being the usual dose and can be repeated after 30 minutes. This drug may be administered orally or sublingually. This can be used in graded doses sublingually to achieve the necessary clinical effect. Rebound hypotension could be a problem if the dose is excessive. It has also been seen to exacerbate the effect of MgSO4. Methyldopa: Reserved for patients with an element of chronicity to their hypertension. Labetelol: One mg/kg of labetelol blocks response to endotracheal intubation without neonatal effects. The drug may be administered in progressively increasing doses (20, 40, 80 mg) every 10-15 minutes to a maximum dose of
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300 mg. This may cause fetal bradycardia, hypotension, and hypoglycemia. Fear of the effects of betablockade on the fetus makes the use of other betablocking drugs in the high risk pregnancies unadvisable. Needs fetal monitoring. This is contraindicated in patients with history of asthma and first degree heart block. This drug improves uteroplacental perfusion, decreases uterine vascular resistance. Sodium Nitroprusside: This drug has limited use due to fear of cyanide toxicity in the fetus. There are also doubts as to its safety in the presence of raised intracranial pressure such as may occur in a patient who has had several convulsions. Nitroglycerine: Acts on venous capacitance vessels. Does not prevent response to intubation. Patients receiving volume expansion are markedly resistant. Initial intravenous infusion rate is 5 mg/min and titrated to desired response by doubling the dose every 5 minutes. Side effects include tachycardia, nausea, vomiting, pallor, sweating, headache and methaemoglobinaemia. Once delivery has occurred, other oral antihypertensive agents such as labetalol or nifedipine can be used to keep systolic blood pressure below 155 mm Hg and diastolic blood pressure below 105 mm Hg. The recommended dose of oral labetalol is 200 mg every 8 hours (maximum dose of 2,400 mg/d), and the recommended dose of nifedipine is 10 mg orally every 6 hours (maximum dose of 120 mg/d). We would prefer oral nifedipine because it offers the benefit of improved diuresis in the postpartum period[16]. Fluid management Fluid management is a challenge in severe preeclamptics and eclamptics complicated by decreased urine output, poor CVP-PCWP correlation, and wide variability of haemodynamic profile. In severe pre-eclamptics and eclamptics, low plasma oncotic pressure and left ventricular dysfunction can combine to produce high incidence of pulmonary oedema and cerebral oedema. Diuretics and the administration of high concentrations of colloid solutions (albumin, hetastarch) should not be used to decrease peripheral edema caused by further depletion of intravascular volume and an increased risk of pulmonary edema and uteroplacental insufficiency. Severe preeclamptics poorly tolerate overhydration (preloading) before regional anaesthesia if ventricular dysfunction is present. They are also sensitive to sympathetic blockade as a result of regional anaesthesia due to decreased blood volume. However, 400-500 colloid preloading prior to regional anaesthesia may reduce the risk of hypotension and fetal distress. 3. Hepatic In hepatic disorders raised enzymes may occur due to
periportal or focal necrosis with large hyaline deposits of fibrin-like material in sinusoids. Decreased synthesis of pseudo cholinesterase may prolong suxamethonium, chloroprocaine or tetracaine. Hyperbilirubinemia, however, is not a common feature. Hepatic dysfunction may form part of the HELLP syndrome, which complicates 0.3% of all pregnancies and up to 20% of women with severe pre-eclampsia. The syndrome comprises haemolysis, increased liver enzymes, and low platelets with epigastric or right upper quadrant pain. Thrombocytopenia (platelets <100,000/mL) and also qualitative platelet dysfunction can occur[20,22,23]. Subcapsular hematoma of the liver can cause intense epigastric pain and, rarely, the liver may rupture. Disseminated intravascular coagulation occurs in 7% of patients with eclampsia but the cause is unclear[23]. More than 50% patients may need blood or blood products if they develop HELLP syndrome. Massive transfusion may be required in some case of HELLP syndrome. These patients may manifest a number of problems associated with massive transfusion. In cases where patients have a coagulopathy, regional anaesthesia is contraindicated. Deferential diagnosis is preeclampsia versus acute fatty liver of pregnancy, viral hepatitis and other hepatic disorders. Assessments and management of the woman diagnosed with HELLP syndrome are the same as for the woman with severe preeclampsia. 4. Renal Glomerular involvement, probably due to a vascular basis of the disease leads to proteinuria. Examination shows subendothelial deposits, electron dense droplets in the glomerular epithelial cells that contain albumin, immunoglobolin, fibrinogen and complement. Oligouria is common due to hypoproteinaemia and decreased renal blood flow rather than a primary renal pathology[24]. This may be due to prerenal cause and may be distinguished from other causes by giving a fluid challenge. But one has to avoid giving repetitive, unmonitored fluid challenges. Dopamine may be started in a low dose 2-3 mcg/kg/min to improve renal perfusion. Progression to acute renal failure is common especially with hypertension and HELLP syndrome. Renal outcomes are usually good. 5. Pulmonary Respiratory assessments are performed to identify signs of pulmonary oedema, respiratory compromise, or magnesium toxicity. Respiratory rate is evaluated for rate quality and pattern, especially if receiving MgSO4, to identify early signs of toxicity. Laboured respiration or use of the accessory muscles is assessed; pulmonary oedema can develop very quickly. Tachypnoea and tachycardia are early signs of evolving pulmonary oedema. Skin color and mucous membranes are assessed for the presence of
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cyanosis, which may indicate problems with oxygenation. Oxygenation status is assessed with pulse oximetry. However, pulse oximetry should not replace clinical assessments. During active convulsion, maternal injury should be avoided. Since the woman may have vomiting, the airway must be protected. Maintain adequate oxygenation. Once the convulsion has stopped and the patient has begun spontaneous respirations, oxygenation status is monitored. If spontaneous respirations are not present, ventilatory support will be required. Minimize the risk of aspiration. The woman should be positioned to facilitate drainage from the mouth. Suction equipment should be readily available and in working order. Also, if supplemental oxygen is being administered by facemask, be aware of the possibility of vomiting and aspiration. Correct maternal acidaemia. Blood gas analysis will allow monitoring oxygenation and pH status. Respiratory acidaemia is possible after convulsion, but sodium bicarbonate is not administered unless the pH is less than 7.10[12]. Ensuring adequate respiratory status is essential. Since all anticonvulsant drugs are respiratory depressants and may interact with each other, polypharmacy should be avoided. Respiratory failure is diagnosed clinically and by blood gas analysis. A fall in PaO2 to less than 60 mmHg or/and a rise in PCO2 to more than 45 mmHg would need mechanical support. Airway is protected with a cuffed endotracheal tube. Ventilation is also required temporarily after emergency lower segment caesarean section or in uncontrollable convulsive states. Once the delivery has occurred the blood gas analysis is satisfactory and convulsions are controlled, and other systems are in an acceptable condition, a decision to wean off is taken. Patient is weaned from the ventilator and is put on T-piece trial. Once the reflexes have returned Table 3: Indications of immediate delivery. 1. Non-reassuring fetal status 2. Vaginal bleeding
and the patient is conscious and oriented (after withdrawal of sedation) and able to breathe around the tube, the trachea is extubated. MANAGING THE NEONATE Ultimate goal of any protocol for management of preeclampsia must be maternal safety first followed by delivery of a live, mature (if possible) newborn in optimal condition (Table 3)[25-28]. Essentially two management options are available: • •
Immediate delivery for maternal benefit and subsequent neonatal intensive care. Pregnancy prolongation (expectant management or 4 hour delay with corticosteroid therapy for maturation of lungs). The study by Witlin, et al has the following results[29].
1. No correlation between severity of maternal disease and fetal outcome. 2. No correlation between fetal variables (5 min APGAR, cord pH, PDA, O2 requirements, necrotizing enterocolitis) and fetal outcome. 3. Incidence of RDS (respiratory distress syndrome) is inversely proportional to gestational age. 4. Expectant management and steroid use did not decrease RDS. 5. Incidence of RDS is directly proportional to cesarean delivery (incidence of cesarean decreased with increased gestation). 6. Birth weight was the most important determinant of survival (IUGR decreased survival). 7. Any delivery after 34 weeks is safe as the lung is mature after this period. LABOUR ANALGESIA Mild to moderate preeclampsia may be allowed to proceed with normal labour. Epidural block may be instituted early if the coagulation parameters are normal. This may be useful in controlling stress and pain. It is also thought that an epidural block may improve the placental intervillous blood flow.
3. Uncontrolled severe hypertension
ANAESTHETIC CONSIDERATIONS
4. Pulmonary oedema
1. Airway assessment to predict a difficult mask ventilation or intubation is a must. Mallampatti scoring must be done prior to anaesthesia. Post convulsion laceration of the tongue or mucosa may be predictive of a difficult ventilation or intubation. Presence of a stridor or excessive facial oedema may be predictive of airway oedema. In these patients it is important to take care that the endotracheal tube used is smaller than usual and
5. Persistent severe headache or visual changes 6. Compromised renal function 7. Platelet count of <100,000/mm3 or raised liver enzymes (AST/ALT) 8. Uncontrolled seizures 9. Attainment of 34 weeks of gestation
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extreme care is taken to avoid trauma during intubation. However, in many of these patients it is not possible to predict all the problems and there may be an unanticipated difficult airway so the anaesthesiologist must be ready with the equipment needed in this situation (introducers, bougie, laryngeal masks, surgical airway, fiberoptic bronchoscopes etc.). Awake intubation may be necessary in predicted difficult airway but nasotracheal intubation requires a normal coagulation status. 2. A rapid sequence induction is carried out and general anaesthesia is preceded with a 3-minute preoxygenation. Theopentone 4-5 mg/kg or etomidate 0.2 mg/kg with suxamethonium (1-1.5 mg/kg) with Sellick’s maneuver should be used for achieving rapid airway access. 3. Haemodynamic response to intubation can cause a dangerous rise in blood pressure and drugs to control this may have to be used in some cases. Lignocaine, betablockers, opioids, nitroglycerine and sodium nitroprusside have been seen to affect the fetus. Newer narcotics such as alfentanil when administered prior to suxamethonium can decrease the haemodynamic response to intubation and has a short duration of action in the fetus. 4. When MgSO4 or nifedepine has been administered to the patient there may be an interaction with the nondepolarising muscle relaxant in causing a prolonged block. Neuromuscular monitoring is preferable in these cases. 5. Regional anaesthesia is contraindicted in patients with abnormal coagulation parameters, patients with a history of convulsions or unconsciousness. The other contraindications to regional anaesthesia also apply in these situations. The patients must be well hydrated prior to anaesthesia as there could be precipitous fall in blood pressure. Newer techniques like the combined spinal epidural are preferable to a single dose spinal as there is a better control over the haemodynamics.
maternal or fetal complications were attributable to any method if steps are taken to ensure careful approach to the method used. 2. Vasopressor and fluid requirements are more with regional anaesthesia. Delivery is the ultimate care for the maternal disease. However, maternal benefits must be weighed against the neonatal risks of preterm delivery. Delivery of infants less than 24 weeks gestation with immature fetal pulmonary profiles result in intensive and prolonged neonatal care associated with significant neonatal mortality and morbidity. CONCLUSION Eclampsia is the commonest obstetritic condition requiring ICU admission in the developing countries. Women diagnosed with the HELLP syndrome or eclampsia present a variety of management issues and problems for the health care provider. Regardless of the diagnosis, severe pre-eclampsia, the HELLP syndrome, or eclampsia can profoundly affect the woman and her fetus. The underlying pathophysiology must be evaluated and treated with both patients in mind at all times. Nurses caring for the woman diagnosed with severe preeclampsia, the HELLP syndrome, and eclampsia must be fully aware of the risk factors, diagnostic criteria, appropriate management regimes, and the potential complications for both the woman and her fetus. The Collaborative Eclampsia Trial has shown that magnesium sulphate is the drug of choice for routine anticonvulsant management of women with eclampsia; a similar study is warranted to establish the antihypertensive drug of choice. REFERENCES
6. Depending on the preoperative problems and the conditions of the patient, postoperative ventilation and supportive intensive care are continued in the postoperative period. All patients with severe preeclampsia need intensive care for 24-48 hours in the postoperative period. The same standard of care must be continued. One must remember that convulsions can occur upto 7 days in the postoperative period.
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