Severe pre-eclampsia and eclampsia

BaillieÁre's Clinical Obstetrics and Gynaecology Vol. 14, No. 1, pp 57±71, 2000

doi:10.1053/beog.1999.0063, available online at http://www.idealibrary.com on

4 Severe pre-eclampsia and eclampsia James J. Walker

MD, FRCOG, FRCP (Edin, Glas)

Professor Department of Obstetrics and Gynaecology, St James University Hospital, Beckett Street, Leeds, UK

The mainstay of the management of severe pre-eclampsia is early referral, stabilization of the mother with antihypertensive therapy and anticonvulsants if required, full assessment of the mother and the baby, and delivery on the best day in the best way. It is to be remembered that delivery is the long-term cure, but most women get worse after delivery and most maternal deaths occur postpartum. It is important that doctors have the training to be aware of the dangers of this condition, guidelines to follow and senior support. Lowering blood pressure has been associated with a reduction in the mortality from cerebrovascular accident and early use of antihypertensive agents is bene®cial to both mother and baby. The main cause of death is now pulmonary oedema, with renal failure a rare complication. It is important that, after delivery, vigilance is maintained and ¯uid replacement is given with care. It is better to `run them dry' than to give ¯uid replacement that may encourage pulmonary oedema. Followup is required with counselling about what has happened and the prospects of recurrence. Key words: pre-eclampsia; eclampsia; hypertension; pulmonary oedema; maternal mortality; antihypertensive drugs; anticonvulsants; ¯uid therapy.

The latest con®dential enquiry into maternity mortality in the UK con®rmed that hypertension in pregnancy remains one of the two most common causes of direct death.1 The number of deaths in the last triennium was 20, exactly the same as was reported for the previous 3 years. However, since 1950, there has been a dramatic fall in the maternal mortality associated with pre-eclampsia/eclampsia (Figure 1), and any further improvement will require even higher levels of vigilance and care. Compared with many other parts of the world, the complications of pre-eclampsia have steadily lessened, the incidence of eclampsia in the UK continually falling2 and now being only 4.9 per 10 000 deliveries.3 These reductions in mortality and morbidity coincided with introduction of the National Health Service and free, generalized antenatal care for all at the point of access. Thus, one of the main reasons for the reduction of maternal morbidity is not the improvement of the management of the acute disease, but the screening and intervention that comes with organized antenatal care and the improved health of the nation. This is the mainstay of obstetric practice, and any changes in antenatal care must maintain this level of vigilance. At the present time in the UK, most hypertensive women are diagnosed early in the disease process when intervention can reduce the incidence of severe disease and eclampsia. A consequence of the reduction in the incidence of the severe disease is the concomitant reduction of the experience of its management obtained by the majority 1521±6934/00/010057+15 $35.00/00

c 2000 Harcourt Publishers Ltd. *

Figure 1. Maternal mortality associated with pre-eclampsia/eclampsia since 1950.

58 J. J. Walker

Severe pre-eclampsia and eclampsia 59 Table 1. The maternal sequelae of severe hypertension in pregnancy. Major Cerebrovascular accident Convulsions Haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) Liver failure Liver rupture Complications of treatment Sedation and aspiration Fluid overload

Occipital lobe blindness Pulmonary oedema Aspiration syndrome Renal failure Deep venous thrombosis Postpartum haemorrhage

Caesarean section

of obstetricians. The average consultant will only see a woman with eclampsia once every 4 years and, even then, usually after the event. This increases the importance of the development of regularly updated consensus guidelines to ensure an adequate level of care. The Con®dential Enquiry persistently reports a high level of inappropriate management. Much of the problem is related to a lack of understanding of the disease process. Pre-eclampsia is more than just hypertension.4 There are many other problems encountered that put the mother's life at risk (Table 1)5, and the guidelines must cover all aspects of the disease, particularly pulmonary oedema, which has now become the main cause of maternal death and morbidity (Table 2).1 As far as the baby is concerned, perinatal mortality and morbidity are related to placental insuciency and the complications of premature delivery.6 The level of maternal blood pressure and the severity of disease are less signi®cant except when they necessitate a premature delivery. Because of these multifaceted problems, the management of severe pre-eclampsia/ eclampsia requires multiple, separately targeted strategies that are part of a step-wise system of management of pregnancy hypertension (Table 3). There needs to be an easy method of referral from the community into a monitoring system7 so that any a€ected woman can be seen early and intervention therapy commenced to reduce the maternal risk and damage associated with more severe disease.8 It is not just high blood pressure that requires intervention: other clinical signs must also be screened for. This is a multisystem disorder with many similarities to an Table 2. The causes of maternal death documented in the Con®dential Enquiries into Maternal Mortality over the past 23 years. Year

Cerebral

Pulmonary

Hepatic

Renal

Other

70±72 73±75 76±78 79±81 82±84 85±87 88±90 91±93 94±96

25 23 21 17 21 11 14 5 7

8 7 4 8 3 12 10 11 9

5 14 5 8 0 1 1 0 3

3 1 0 0 0 1 0 1 0

6 4 3 3 1 2 2 3 1

Total

144

72

37

6

25

60 J. J. Walker Table 3. The step-wise management of pregnancy hypertension. Screening Screening women for the risk or signs of hypertension at the antenatal clinic Refer those at risk for monitoring in an antenatal day unit Prior to delivery Follow regularly updated management guidelines Early involvement of senior medical sta€ Lower blood pressure if required Prophylactic steroid administration if the pregnancy is of less than 34 weeks' gestation Consider the need for magnesium sulphate Continuing monitoring for signs of disease progression Delivery of the baby on the best day, in the best way and in the best place

in¯ammatory disease.9 This leads to a multiplicity of clinical signs and symptoms. The development of proteinuria, increasing oedema or the addition of clinical symptoms such as headache, visual disturbance or abdominal pain should lead to immediate admission and further investigation. Similarly, any pregnant woman with a presenting symptom of headache, abdominal pair or nausea, or who is just feeling unwell, should have her blood pressure checked and her urine tested for proteinuria as pre-eclampsia can be present in many guises. If there is concern, immediate referral to the obstetric unit is mandatory to allow full assessment and a consideration of intervention therapy and the appropriate timing of delivery.

IMMEDIATE ASSESSMENT AND CARE On ®rst presentation, it is the maternal hypertension that is the primary concern and needs to be controlled. It was once thought that lowering the blood pressure was potentially dangerous for the baby, and there were reports to support this.10,11 Since 1980, there has been an increase in the use of antihypertensive drugs by obstetricians12, and this has been associated with a reduction in maternal and neonatal death from pre-eclampsia, particularly in the number of maternal deaths related to cerebral pathology (see Table 2 above).1 A recent meta-analysis of antihypertensive therapy in pregnancy has shown that early treatment reduces not only the incidence of hypertensive crisis, but also neonatal complications such as respiratory distress syndrome.13 Therefore, an early aggressive use of antihypertensive therapy to stabilize the maternal condition would appear to be bene®cial not only to the mother, but also to her baby. The meta-analysis does not compare di€erent drugs. It probably does not matter which drugs are used as long as attendant sta€ are experienced in their use and the drugs are thought to be safe. The most common drugs used in the UK are hydralazine, methyldopa, labetalol and nifedipine.11,12 No one therapy can control all patients, and increasing doses and combinations of drugs are usually required.14 Care should be taken not to reduce the blood pressure too quickly as side-e€ects can occur. Intravenous drugs should be avoided if the woman can tolerate oral therapy. The latter is commonly used in hypertensive crises in non-pregnant patients.15 In randomized trials, oral labetalol16 and nifedipine17 have been shown to be as e€ective as and more predictable than parental hydralazine. Oral therapy appears to provide a smoother, more predictable

Severe pre-eclampsia and eclampsia 61 Table 4. A suggested antihypertensive regimen. Acute management Labetalol 200 mg orally repeated hourly until control is achieved or Nifedipine 10 mg orally (not sublingual) or Labetalol 50 mg by slow intravenous bolus followed by Labetalol infusion starting at a rate of 60 mg per hour doubling every 15 minutes until control is achieved or a maximum of 480 mg is reached Starting daily dose for chronic therapy Labetalol 200 mg three times daily increasing to Labetalol 300 mg four times daily with the addition of Nifedipine retard 10 mg twice a day increasing to Nifedipine retard 60 mg per day in divided doses

fall in blood pressure. The use of intravenous hydralazine is associated with a sudden drop in blood pressure, with abnormalities of fetal heart rate.18 Studies have suggested that this may be due to a combination of acute vasodilatation in women with a reduced plasma volume. To reduce this complication, hydralazine has been used in combination with plasma expansion, but the results are no better than those with oral antihypertensive therapy alone.19 Oral labetalol and nifedipine appear to be at least as good as hydralazine16,18 without the need for plasma expansion and invasive monitoring. In Yorkshire, there is a consensus protocol that uses oral labetalol with a starting dose of 200 mg three times daily (Table 4). This can be steadily increased to a maximum of 300 mg four times a day. If control is not achieved, 10 mg oral nifedipine retard can be given twice a day, increasing to a maximum of 60 mg per day. These drugs have been shown in animal experiments not to reduce placental or maternal peripheral blood ¯ow in human pregnancy.11 Nifedipine can also be used as the primary therapy, but care should be taken as, especially with sublingual usage, sudden falls in blood pressure can sometimes be seen.20 The oral route is safer and as e€ective. The combination of nifedipine and magnesium sulphate was thought to be potentially dangerous because of synergism, but many centres have had extensive experience with this combination without any problems. If oral therapy is unsuccessful, intravenous labetalol 50 mg given by slow bolus injection followed by labetalol infusion will lower the blood pressure in the majority of patients.21 The aim of therapy is not to normalize the level, but to stop the rise of blood pressure and achieve a moderate fall, a drop of around 10 mmHg diastolic pressure being the primary aim. Once this has been achieved, there is usually a need for an increase in drug dosage every few days as this is a progressive disease. Since women with severe pre-eclampsia/eclampsia often present acutely out of clinic hours, it is important that all sta€ are familiar with the management guidelines and the aims of therapy. Blood pressure control must, if at all possible, be achieved prior to delivery, but especially before intubation for general anaesthetic, before caesarean section as an acute blood pressure rise can occur.22

62 J. J. Walker

THE USE OF ANTICONVULSANT AGENTS Although eclampsia is a common presentation in many parts of the world, it is now a rare occurrence in the UK, occurring in 1 in 2000 of all pregnant women.3 If people do su€er a convulsion, the majority of patients convulse only once.5 The risks to the mother and baby from eclampsia appear to be more related to the degree of preexisting pre-eclampsia than to the eclampsia itself. Although evidence of prodromal signs, particularly headache and abdominal pain, is present in many women prior to the convulsion, about 20% of patients convulse unexpectedly, often with normal blood pressure, and no sign is speci®c for the development of eclampsia.5 The widely used clinical assessment of hyperre¯exia has never been demonstrated as being an accurate predictor even though it is widely used as such. However, it is of great value as a clinical measure of magnesium toxicity. If the re¯exes are absent, magnesium toxicity should be suspected and the medication stopped. If convulsions have occurred, anticonvulsant therapy is required. A large multicentre study has shown that magnesium sulphate is superior to both phenytoin and diazepam.5 Both the reconvulsion and maternal death rates were found to be signi®cantly reduced compared with either diazepam or phenytoin. Although there is now no doubt what preparation to use (Table 5), it is important to note that no treatment will completely prevent seizures, reconvulsion rates varying between 5% and 20%.5 Both the intravenous and intramuscular regimens used in the study were similar to those previously published. There is no evidence to suggest that one route is superior to any other. Both regimens use a slow intravenous loading dose of 5 g magnesium sulphate that can be used to treat the convulsion. This should be given over 20 minutes as a faster bolus may produce cardiac arrest. There is no need to use diazepam initially to stop the seizure. Whether the intramuscular or the intravenous maintenance dosage is used depends on the preference and facilities of the centre. The intramuscular route has the advantage of ease of use, although intravenous therapy may provide better blood levels. Many obstetricians are concerned about the possibility of magnesium toxicity. The study cited here used clinical evaluation alone, showing that the toxicity did not occur and the side-e€ects from magnesium were no worse than Table 5. Anticonvulsant therapy to be used in the eclamptic patient. Either the intravenous or the intramuscular regimen can be used. Intravenous regimen Loading dose of 5 g intravenously over 20 minutes Infusion of 1 g per hour for 24 hours Intramuscular regimen Loading dose of 4 g intravenously over 20 minutes 5 g into each buttock intramuscularly A further 5 g intramuscularly every 4 hours (Provided the respiratory rate was over 16 per minute, the urinary output over 25 ml per hour and knee jerks were present) For recurring convulsions A further 2±4 g given intravenously over 10 minutes If magnesium toxicity is suspected Suggested by the absence of re¯exes 1 g calcium gluconate should be given

Severe pre-eclampsia and eclampsia 63

those from diazepam, being signi®cantly less than those found with phenytoin. Therefore, using these dose regimens, there is no need to check magnesium levels or to have this facility available at all times. Magnesium levels are useful in the management of treatment failure to test whether an increased dosage might be of bene®t. There is thus good evidence to support the ecacy of magnesium sulphate therapy for women with eclampsia.23 However, the role of prophylactic magnesium sulphate in women with pre-eclampsia is less clear. If in doubt, it is probably safer to give it than not, but magnesium is not without its own risks and, in some series, the only deaths have arisen from magnesium toxicity. The risk of eclampsia in women with preeclampsia is probably around 1 in 200, and there is no evidence that magnesium will reduce this.24 However, if a prophylactic anticonvulsant is to be used, magnesium sulphate is the drug of choice.25 There have been concerns expressed over the e€ect of magnesium therapy on the ecacy of labour. Compared with phenytoin, magnesium sulphate given for the intrapartum treatment of pregnancy-induced hypertension did not signi®cantly a€ect labour outcome26, but did necessitate a higher dose of oxytocin.27

WHAT TO DO ONCE THE PATIENT HAS BEEN STABILIZED Once the patient has been stabilized, a plan of action should be made by a senior doctor. After convulsion has occurred, the continuation of pregnancy cannot be justi®ed in the UK setting, but there is no hurry to deliver the baby. The mother needs to be assessed and stabilized prior to delivery as this will reduce the severity of her postpartum exacerbation. The fetus may present with acute distress after a maternal convulsion, but will quickly recover. A carefully planned delivery over the next few hours should be carried out so that all the relevant carers are in place and ready to look after both mother and baby. Transfer of the mother to a more appropriate setting may further improve the ability to care for her and her baby after delivery. In the absence of convulsions, prolongation of the pregnancy is possible, in most cases, for an average of 15 days.11 This has been shown to improve the outcome for the baby without detriment to the mother. Rushing the delivery in the maternal interest may not be of bene®t to the mother and can lead to increased morbidity for the baby, as it is the gestation at delivery more than any other parameter that in¯uences the baby's outcome.6 Even in cases of HELLP syndrome, there is no di€erence in outcome compared with gestation-matched controls with severe pre-eclampsia alone19 or those born prematurely for other reasons.28 However, it is important that the mother's condition is stable so that the prolongation of pregnancy does not jeopardize her life. The situation should be constantly reassessed and the management plan reviewed by a senior doctor (Table 6). A woman who is stable may not remain so. The plan of management is more along the lines of `not needing delivery now' rather than `let's deliver her tomorrow'. If delivery within the next few days is thought to be a possibility and the gestation is less than 34 weeks, prophylactic steroids should be given to induce fetal lung maturity. Two doses of dexamethasone 12 mg intramuscularly given 12 hours apart is the regimen used in Yorkshire guidelines. The aim is to prolong the pregnancy for at least 48 hours to achieve maximum e€ect, although even if the delivery is earlier, some bene®t will be gained.

64 J. J. Walker Table 6. Management plan for the continuing care of the woman with severe pre-eclampsia. Maternal management Keep blood pressure controlled with antihypertensive drugs Use the average of four blood pressure readings for monitoring At least twice-weekly serum uric acid level, platelet count and liver function tests Test for the presence of proteinuria with or without quanti®cation Fetal management Prophylactic steroids given if the gestation is below 34 weeks Initial ultrasound assessment of fetal weight Doppler ultrasound assessment of umbilical blood ¯ow velocity twice a week Daily cardiotocographs At least twice-weekly ultrasound for liquor volume Care after delivery Continuing close monitoring of the mother within a closely monitored environment by experienced carers Careful ¯uid balance and early use of diuretics if required Reduction of antihypertensive agents as indicated Stop anticonvulsant therapy after 48 hours if stable Follow-up Long-term follow-up to make sure that the problem with blood pressure resolves Discussion concerning what has gone on and its signi®cance for the future Referral for counselling to local experts and future planning

Delivery should be carried out before 48 hours have elapsed if there are strong maternal or fetal reasons. After 48 hours, if a further prolongation for more than a week is not thought to be achievable, delivery should be carried out when the mother is stable and the baby is well and has received maximum bene®t from the prophylactic steroids. Transfer of the mother prior to delivery may be necessary for the optimum care of the mother or her newborn, possibly premature baby. ASSESSMENT OF THE HYPERTENSIVE WOMAN (TABLE 6) Antihypertensive therapy lowers blood pressure and should not be expected to do anything else. It is important to emphasize that if pregnancy is going to be continued, close monitoring of the mother is required using blood pressure monitoring, proteinuria, maternal uric acid levels29 and platelet count30 to monitor disease progression. Fetal well-being should be followed using cardiotocography and ultrasound for fetal growth, umbilical artery Doppler velocity waveforms and liquor volume estimations. Blood pressure measurement Abnormality of blood pressure is, for obvious reasons, the primary diagnostic criterion in hypertension in pregnancy. However, blood pressure is a variable and can ¯uctuate on a minute-to-minute basis.31 A single, elevated blood pressure reading thus needs to be con®rmed before management decisions are made.14 The average of several readings allows a more accurate estimation of the true blood pressure measurement. Automatic blood pressure recorders often measure a diastolic blood pressure several mmHg lower than a normal sphygmomanometer, and this should be taken into account when these machines are being used in the acute situation.

Severe pre-eclampsia and eclampsia 65

The presence of hypertension can, in itself, put the mother at increased risk of cerebrovascular accident, but it is the presence of systemic involvement that is the hallmark of pre-eclampsia as it implies that the hypertension is part of a progressive disorder. The major morbidity factors such as pulmonary oedema, liver failure and coagulation defects are associated with these systemic changes. Proteinuria The testing of the urine for proteinuria is the simplest and most available test. The association of protein with eclampsia has been known for over 100 years. Urine stick testing will overestimate the presence of proteinuria, and this should always be con®rmed by a 24-hour collection for quanti®cation. The importance of proteinuria is that it helps to con®rm the diagnosis of pre-eclampsia with the concomitant increased risks.6 The proteinuria is a sign not of renal damage but of the presence of a capillary leak that is associated with the development of oedema ¯uid throughout the body. Once protein is present, a change in the amount does not re¯ect increasing severity of disease and should not in¯uence the decision to deliver on its own, but it can signal an increased risk of pulmonary oedema. Lowering blood pressure is associated with a reduction in proteinuria; similarly this does not imply that the risks have diminished, but instead re¯ects a reduced renal perfusion pressure. Uric acid measurement Uric acid rises in pre-eclampsia and is a better predictor of fetal morbidity than is blood pressure itself.29 The reason for the rise in uric acid is not totally clear but appears partly to be caused by renal tubular function impairment, reducing its excretion. This renal involvement is probably the result of renal medularly ischaemia and is not a sign of renal failure, urea and creatinine levels both remaining normal until late in the disease process. Some of the rise in uric acid is due to increased production secondary to tissue damage caused by ischaemia. Therefore, uric acid is partly a surrogate marker of tissue involvement in pre-eclampsia and a useful adjunct to other monitoring tests. Serial testing is of particular bene®t as a rising level is indicative of disease progression and increased risk. Platelet count Platelet counts fall in pre-eclampsia and are associated with progressive disease and worsening outcome.30 In recent years, the combination of Haemolysis, Elevated Liver enzymes and Low Platelets has been described as the HELLP syndrome.32 Although this is undoubtedly associated with increased maternal morbidity, it is not a new phenomenon, but instead a new description of previously described and accepted pathological ®ndings and is a marker of severe systemic involvement. Serial samples should be taken to observe developing trends. Falling platelet counts are of concern and can give some guidance on the timing of the delivery. If a platelet count of below 100 is found, a full coagulation screen, blood ®lm and liver function tests should be carried out as this can give further information about the progression of the disease and the future maternal risk.28 The presence of HELLP syndrome is particularly worrying and usually implies the need for delivery, although cases of conservative management have been reported.33 If the platelet count is higher than 100, it is

66 J. J. Walker

unlikely that the coagulation screen will be abnormal. In such a case, there is no need to carry out a coagulation screen and no risk in the use of epidural analgesia. Liver function tests These are not true liver function tests, but are measurements of enzymes contained largely in liver cells. The disruption of these cells leads to release of enzymes into the circulation and hence a rise in their levels. The most sensitive change is seen in aspartate transaminase (Ast), but there is also a rise in alanine transaminase (Alt), which is easier to measure in an emergency laboratory. A rise in liver enzyme levels is always signi®cant and needs to be followed carefully, Severe liver impairment can be associated with liver swelling, which causes the epigastric pain and can lead to liver rupture, a rare but potentially fatal outcome. In pre-eclampsia, disseminated intravascular coagulation is a rare complication in the absence of an abruption. The coagulation defects seen are usually related to HELLP syndrome, liver function impairment leading to an intrinsic coagulation defect and low platelet count. The loss of red cells is due to intravascular haemolysis caused by an increased red cell fragility possibly associated with free radical damage.34 ASSESSMENT OF THE FETUS (TABLE 6) The assessment of the maternal disease does not give accurate information about the well-being of the baby. Once the mother has been stabilized, speci®c fetal assessment tests should be carried out. The main risks to the fetus are placental insuciency and prematurity. Investigations are directed at the assessment of fetal health, fetal growth and placental blood ¯ow. Cardiotocography Cardiotocography is the mainstay of fetal monitoring in most units. It gives information concerning fetal well-being at that time, but has little predictive value. It can be repeated regularly and easily without the need for expensive equipment or highly skilled personnel, and can be particularly reassuring to the mother herself. Although tracings from fetuses less than 30 weeks' gestation can be misleading, it is the change in the trace that is most informative. As long as the tracing is reactive with good variability, there is no evidence of fetal hypoxia. If accelerations or variability are lost, this implies a deterioration in the fetal state, and the presence of decelerations must be seen as sinister at any time. Cardiotocography should be repeated as often as thought necessary depending on the severity of the situation, but taking daily tracings from women hospitalized on antihypertensive therapy would seem sensible. Fetal ultrasound assessment An ultrasound assessment of fetal size is valuable as a one-o€ measurement to assess fetal growth at the time of the initial admission. It also gives the paediatricians useful information about the expected fetal weight if the baby is to be delivered, as well as allowing estimates of the chances of survival of the baby that can be used in a discussion with the parents about management decisions. Serial growth studies are of

Severe pre-eclampsia and eclampsia 67

less value as they should not be carried out more often than every 2 weeks and the average length of prolongation of pregnancy in severe disease is only 15 days.35 Liquor volume estimation is of less value in earlier gestations where close fetal assessment is usually being carried out36, although reduced liquor volume is associated with fetal growth restriction. Serial estimations are of value as a decreasing volume of liquor can be indicative of increasing fetal compromise. Placental blood ¯ow Reduced uterine artery Doppler end diastolic ¯ow is associated with an increased incidence of placental insuciency and pre-eclampsia.37 It can be used as a screening test in normal pregnancy. In established disease, it is of less value38, but it still can give an indication of whether fetal growth restriction is likely to be present. Umbilical Doppler artery assessment is of greater value39 where serial investigations can be used to follow pregnancies under treatment. If end-diastolic ¯ow is present, therapy can be continued in an attempt to prolong the pregnancy as the baby will normally be able to tolerate a prolongation of pregnancy and maternal antihypertensive therapy.39 Monitoring protocol (Table 6) Although single tests can give information about maternal and fetal well-being, serial sampling adds to this by demonstrating the rate of progression. Proteinuria should be quanti®ed and serial uric acid levels and platelet counts taken at least on a twiceweekly basis. A cardiotocograph should be carried out daily, and at least twice-weekly ultrasound estimations of liquor volume and umbilical artery Doppler velocity waveforms should be made. A particular area of concern is that of liver impairment and the development of HELLP syndrome. Liver function tests or a minimum of at least Alt or Ast level should be carried out on a twice-weekly basis. This, along with the platelet count, will screen for early signs. If the liver function tests and platelet count remain normal, HELLP syndrome and coagulation abnormalities are not present. If HELLP syndrome is thought to be developing, a full coagulation screen and a blood ®lm, looking for fragmented red cells and evidence of haemolysis, should be carried out. PLANNING THE DELIVERY Delivery is the ultimate cure for pre-eclampsia, the timing of delivery a€ecting the outcome for both mother and baby. However, most maternal deaths occur postpartum. A rushed delivery in an unstable patient adds to rather than reduces her risk and is often associated with maternal mortality.1 A delay in delivery in a sick patient may also be associated with maternal death. Any transfer of the woman should be at an early stage while she is stable, and communication should occur between senior doctors in each hospital. If delivery has been decided upon before 32 weeks, it should be carried out by elective caesarean section unless this is more dangerous for the mother. A long induced labour can add to the problems of ¯uid overload and the diculties of blood pressure control, vaginal delivery being successful in fewer than 50% of cases.40 If it occurs after 34 weeks' gestation, a vaginal delivery is aimed for, particularly when the probability of this being successful has been greatly increased by the use of vaginal

68 J. J. Walker

prostaglandins. Antihypertensive therapy should be continued throughout labour to help to control blood pressure. The choice of anaesthetic in caesarean section is important. General anaesthetic can add to the risk to the mother since intubation and extubation can cause a rise in both systolic and diastolic blood pressure as well as heart rate.22 An epidural or spinal block would seem far safer, allowing delivery to take place with the patient awake, and also speeds recovery. Care should be taken that the ¯uid load is kept to a minimum, and a colloid solution may be preferable to a crystalline one which passes quickly across the capillaries into the interstitial space. Women with pre-eclampsia already have an increase of ¯uid in this compartment and are extremely sensitive to excessive ¯uid.41,42 During labour, an epidural is also bene®cial, but not to lower blood pressure as this is a pathological rather than a physiological e€ect. By allowing adequate pain relief, it can stop the rise in blood pressure often associated with labour. It also allows a planned delivery and easy transition to caesarean section if this is deemed necessary. There is no reason routinely to shorten the second stage of labour by instrumental delivery as long as the mother is pushing well and remains stable. After delivery, drugs containing ergometrine should not be used in the third stage of labour, intravenous Syntocinon being the preferred option. POST-PARTUM CARE Since most maternal death and signi®cant morbidity occur after delivery1,2, continued close monitoring is required in a suitable environment. An initial improvement is often seen, but around 60% of women will to some extent worsen within 48 hours. Women with severe disease should be kept in the high-dependency areas and not be transferred to the postnatal wards until their parameters begin to return to normal. With the increased use of blood pressure control and the reduction of cerebral bleeding as a cause of death, the main cause of maternal mortality in this condition is now pulmonary oedema (see Table 2 above)1, probably caused by various underlying mechanisms within the woman with pre-eclampsia, including a low albumin level and an increased capillary leakage.41,42 Although labetalol has been blamed, since it may interfere with cardiac output, studies have shown that it is an increase in interstitial ¯uid volume rather than a reduction in cardiac function that is at fault.42 The risk of pulmonary oedema is aggravated by exogenous ¯uid given in the belief that these women are at risk of renal failure. Renal failure is, in fact, unusual in pure pre-eclampsia and is usually associated with additional problems such as haemorrhage and sepsis.43 If it does occur, the morbidity and mortality are low (see Table 2 above) as it is usually an acute tubular necrosis that can be managed easily.43 Post-delivery, a relative oliguria is not uncommon, occurring in about 30% of patients with severe disease. This does not require therapy as urinary output will recover in its own time. If there is any doubt about renal function, urinary osmolality can be checked. If the urine is concentrated, renal function is satisfactory and the reduced output is related to a reduced renal perfusion, which will gradually improve over time. If the urine is not concentrated, renal failure is present and a renal failure regimen should be put in place. There is no evidence, however, that oliguria, especially in the presence of concentrated urine, leads to renal failure. Fluid challenges are potentially dangerous in pre-eclampsia as much of the ¯uid will be lost from the vessels into the interstitial ¯uid, aggravating the existing tissue oedema. If ¯uid is to be given, colloid should be used up to a maximum of 500 ml and not repeated unless an

Severe pre-eclampsia and eclampsia 69

adequate urinary response has been achieved. In Yorkshire, our initial analysis of the ®rst 40 women with severe pre-eclampsia managed by our consensus guidelines showed that the only women who experienced pulmonary oedema were those given a ¯uid challenge because of a reduced urinary output. Invasive monitoring is usually not necessary, and centre venous pressure (CVP) lines can be misleading.44 In pre-eclampsia, pulmonary oedema, because of increased interstitial ¯uid, can occur in the presence of a low CVP. If a central line is used, it is important that the CVP level is no higher than 5 mmHg or 7 cm H2O. If the CVP is higher than this, diuretics should be used to reduce it. One of the best methods of assessing pulmonary oedema is the continuous measurement of oxygen saturation using a pulse oximeter. If there is a requirement for facial oxygen to maintain an adequate oxygen saturation, there is probably pulmonary oedema present and a diuresis will improve the oxygen carriage. It is far safer and more sensible to run a patient `dry' and restrict intravenous ¯uids than to run the risk of pulmonary overload. Total ¯uid replacement should not exceed an hourly rate of 80 ml. Most of the problems of ¯uid overload begin around 16 hours after delivery, severe problems occurring between 24 and 48 hours. This is associated with a failure of the normal postpartum diuresis. If the patient is in positive balance or there is evidence of pulmonary oedema, 40 mg frusemide should be given, which usually produces an adequate urine output but can be repeated if necessary. This can be followed by 20 g mannitol to reduce tissue ¯uid. This will lower the probability of pulmonary oedema, increase oxygen saturation, reduce cerebral oedema and improve blood pressure control. Therefore, after delivery, management should be aimed at maintaining blood pressure control and carefully monitoring the ¯uid balance. If convulsions occur, anticonvulsant therapy can be added. The majority of postnatal convulsions occur within the ®rst 24 hours, so anticonvulsant therapy is usually continued for 48 hours postdelivery. If the patient is well, especially if a prophylactic anticonvulsant is being used in the absence of any convulsions, this therapy can be stopped at 24 hours. Antihypertensive therapy should be reduced after delivery depending on the blood pressure. There may be a signi®cant drop within the ®rst 24 hours with a rise again after 48 hours. Antihypertensive drugs may be necessary for some weeks after delivery. It has been claimed that postpartum curettage can be curative in women with persistent disease.45 However, follow-up studies have demonstrated that nifedipine therapy is as good as uterine curettage in accelerating recovery from severe preeclampsia, although uterine curettage may be more e€ective in rapidly resolving the thrombocytopenia associated with severe pre-eclampsia.35 An acute re-presentation can occur some days after apparent improvement, although this is uncommon.46 Women with persistent headaches, malaise, nausea and vomiting are more likely to have a recurrence of their symptoms and should be assessed accordingly.47 FOLLOW-UP The patient should be followed up until normal blood pressure has returned. The diagnosis of the underlying cause of the hypertension in pregnancy may not be apparent until after the pregnancy is over. If blood pressure has not returned to normal by 6 weeks postpartum, the patient should be referred for further investigation as the cause is unlikely to have been pre-eclampsia. A postnatal visit should be carried out to assess the recovery of the woman and to discuss the signi®cance of what

70 J. J. Walker

happened and what might happen in the future. It should be remembered that women with severe pre-eclampsia have a 30% chance of a recurrent problem, but it is usually less severe and occurs 2±3 weeks later than in the previous pregnancy.

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