Pre-eclampsia, eclampsia and the anaesthetist

Pre-eclampsia, Eclampsia and the Anaesthetist

P. R. Howell

and A. P. Rubin

frequently received a variety of treatments, and this creates difficulties in comparing the results of different studies. He stresses the need for standardisation and also for large multi-centre trials to be established. The traditional triad of proteinuria, oedema and hypertension are no longer considered essential for the diagnosis of PET by most workers, and oedema is omitted from most current criteria since it commonly occurs in normal pregnancy, and is difficult to quantify. Sibai, in the USA, advocates the use of an elevated diastolic blood pressure (DBP), using Korotkoff phase IV sound, and the presence of >3OOmg proteinuria in a 24-h period.2 In the UK, the diagnosis is usually based on the criterion of an elevated DBP above 90mmHg, although this will inevitably include some women with chronic (nonpregnancy related) hypertension.3 Redman suggests the combined use of an early DBP below 90mmHg, an increase of at least 25mmHg, and a maximum reading of at least 90mmHg, as criteria which more accurately identify the women with PET.”

Pre-eclampsia (PET) is a common condition which complicates approximately 15% of primigravid pregnancies. Eclampsia, much less common, occurs in approximately 0.04% of deliveries. Since the publication of the first Report on Confidential Enquiries into Maternal Deaths in England and Wales (CEMD) in 1955. these two interlinked conditions have repeatedly been shown to be amongst the most frequent causes of maternal death, and associated with significant maternal and fetal morbidity. * Whilst the aetiology is still poorly understood, the clinical consequences as a multi-system disorder are much more clearly appreciated. As such, they are of considerable relevance to the anaesthetist who may become involved in the management of these patients if simple conservative therapy fails during labour or delivery. Since the severe forms of these conditions are rare but complex and life-threatening, and individual obstetricians, midwives and anaesthetists are likely to have had little previous experience in their management, it has been recommended that each Region should establish an advisory team with special expertise.’ This does not yet appear to have been achieved by all Regional Health Authorities.

Mortality Over the past 30 years there have been considerable improvements in the provision and quality of perinatal care, which are reflected in the fall in the overall maternal mortality rate from 69.1 (per 100000 total births) in 1955 to 8.6 in 1984. However, although the absolute number of deaths from PET and eclampsia has fallen to 25 in the last triennium reported, these disorders remain, with pulmonary embolism, the most common direct causes of maternal death.’ Twenty-one of these patients died of cerebral complications, which implies ineffective control of blood

Diagnosis of pre-eclampsia There is much confusion regarding the definition of PET and there are presently no internationallyagreed diagnostic criteria. Sibai, in a review of world literature, highlights the inconsistencies in terminology, blood pressure measurements, diagnosis and populations studied.2 Patients within studies have Dr P. R. Howell, Dr A. P. Rubin, Department of Anaesthesia, Charing Cross Hospital, Fulham Palace Road, London W6 Current Ana&mia 0

1991 Longman

and Critical Care (1991) 2. 101-107 Group

UK Ltd

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pressure. In addition, three patients in this period died after presenting in late pregnancy with vomiting and upper abdominal pain or headache, in the presence of normal or only mildly elevated blood pressures. These are important symptoms of fulminant disease which may rapidly progress to severe hepatic impairment and eclampsia. Their significance in the third trimester despite the lack of hypertension should not be underestimated, and these patients need careful monitoring of their hepatic function, blood pressure and level of consciousness, all of which may alter rapidly.

Patho-physiology The aetiology of PET is still poorly understood, although present thought suggests there to be an autosomal recessive genetic predisposition which promotes an immune response within the placenta. Failure of normal placental implantation leads to reduced uteroplacental perfusion and function. This results in reduction in prostacyclin formation, and a relative rise in the vasoconstrictor, thromboxane AZ, which gives rise to endothelial damage, loss of plasma volume, intravascular coagulation and diminished organ perfusion. The pathophysiological background to PET is well described in an excellent review article by Brown.4 The histological post-mortem changes seen include cerebral haemorrhages and areas of cerebral oedema, placental thrombotic lesions, pulmonary oedema, and a wide range of hepatic changes. Although hepatic necrosis was the cause of death in only one patient in the latest triennium, it was seen on autopsy in eight patients, and it would appear to be a much more common occurrence in PET than is generally realised.’

Prevention of pre-eclampsia Exciting advances are being made in the field of prevention, and several studies have observed a reduced incidence of PET in women at high risk who were given low-dose aspirin during pregnancy. The appropriate dose of aspirin is, as yet, undetermined, but 50-1OOmg daily would appear to suppress the production of thromboxane AZ from platelets, whilst having a much lesser effect on prostacyclin. The large, multi-centre ‘CLASP’ (Collaborative Lowdose Aspirin Study in Pregnancy) trial is presently under way in the United Kingdom in order to evaluate the benefits and safety of aspirin in the antenatal period. In spite of excellent early results, Cunningham and Gant, in a leading article, have counselled caution in the prophylactic antenatal prescribing of aspirin until further result are obtained.5

Predictive testing in pre-eclampsia A reliable predictive test for PET would be of immense value in isolating those patients who might benefit most from prophylactic measures in pregnancy, and also those who may need closer antenatal monitoring. Unfortunately, although a great number of clinical, biophysical or biochemical tests have been proposed, the wide scatter of results and lack of agreement between tests suggest that most are inappropriate. O’Brien proposes that the most reliable risk factors are nulliparity and a positive family history, and that the rollover test (positive for PET where the DBP increases when the patient changes from the left lateral recumbent position to supine) is the most effective in vivo test.6 In addition, plasma fibronectin concentration, and the urinary calcium: creatinine ratio, are new tests which need further investigation, but appear to hold promise for the future. In established PET, abnormal maternal creatinine, platelet, bilirubin and aspartate transaminase (AST) levels will detect the development of sub-clinical Elevated maternal levels of organ dysfunction. plasma urate have been shown to correlate with the risk of fetal mortality and are widely used as an indication for early delivery.’

Clinical problems Fluid management

It is well established that the pre-eclamptic patient has a reduced intravascular volume in spite of a frequently normal central venous pressure (CVP) and pulmonary artery wedge pressure (PAWP), and this suggests that the vascular capacitance is also reduced. Venoconstriction results in an increase in right-sided filling pressure (CVP), transudation of fluid into the interstitial space (causing oedema) and a reduction of intravascular volume.8 Superimposed on this is the effect of hypoproteinaemia, and reduced plasma oncotic pressure, which may lead to tissue or of these pulmonary oedema. The management patients is not easy, and there were three deaths in the latest triennium due to fluid overload.’ Expert advice on intravenous fluid administration is needed in these sick patients. In a study of eight patients with severe PET, Wasserstrum et al showed that rather rapid infusion of 500ml5% albumin lead to a reduction in systemic vascular resistance (SVR), a rise in cardiac output, and maintenance of the mean arterial pressure.g Unlike the systemic circulation, though, there was no concomitant fall in pulmonary vascular resistance, and the mean pulmonary artery (PA) pressures rose significantly. They were careful to use patients whose PAWP were less than 12mmHg, and concluded that acute volume expansion in these patients may attenuate the unstable hypotensive responses to

PRE-ECLAMPSIA, ECLAMPSIA AND THE ANAESTHETIST

vasodilator agents that is seen in PET. Belfort showed similar results with plasma volume expansion, particularly when followed by vasodilation with dihydralazine, whereupon a fall in SVR, PAWP and blood pressure were accompanied by a rise in cardiac index.lO Brown advocates the use of volume expansion except in the presence of significant oedema, since this is potentially the subset of patients with increasd capillary permeability at greatest risk of pulmonary oedema if overloaded.4 These and other studies suggest that providing the PAWP is not allowed to rise abnormally, controlled volume expansion may be beneficial in PET. The question of whether to use crystalloid or colloid solutions is still unclear, and the traditional choice of albumin infusion is presently under question. Although this may improve the plasma oncotic pressure (POP), and theoretically reduce the risk of pulmonary oedema by increasing the POP-PAWP gradient, other factors may be involved.” Transpulmonary leakage of large protein molecules may occur in PET which predisposes to the development of pulmonary oedema, particularly if further exogenous fluid is given. ‘* In addition, p lacental blood flow in the hypoalbuminaemic, pre-eclamptic patient may not improve with intravenous albumin infusion.13 Cotton, in the USA, now advocates not attempting to correct the POP with colloid unless it is less than or equal to 12mmHg or a prolonged negative POPPAWP gradient is present.‘” Colloid solutions are also more frequently associated with anaphylactoid reactions especially when rapidly infused, and hence, on balance, crystalloid solutions may be more appropriate to use for pre-loading these patients prior to epidural anaesthesia.

Renal function

Oliguria is a common complication and likely to be a result of both intravascular hypovolaemia and renal hypoperfusion. Clark et al described a subset of oliguric patients with high cardiac outputs and adequate filling pressures, in whom there appeared to be a degree of selective renal arterial spasm.15 The administration of hydralazine and, where appropriate, fluids led to improvement in the oliguria. Renovascular doses of dopamine (l-5 kg. kg-‘.min-‘) have been used in oliguric patients to improve the urine flow, presumably by acting preferentially on renal dopaminergic receptors.16 In this small study, there was a concomitant rise in cardic output associated with a lowering of the SVR and a stable blood pressure. The renovascular benefits of dopamine in sick non-obstetric patients is well accepted, and larger studies are needed to confirm its role in the oliguric pre-eclamptic patient. In severe PET, acute renal failure requiring dialysis is not uncommon.‘7

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Cardiovascular monitoring

There has been considerable debate regarding the need for invasive monitoring in severe PET to guide haemodynamic manipulation for control of blood pressure, urine output or during anaesthesia. In addition, the indications for PA monitoring in preference to CVP measurement are still contentious. Two relatively large studies confirm there to be a spectrum of haemodynamic profiles associated with severe PET, with the majority of patients having normal PAWPs, high-normal or elevated SVRs and hyperdynamic left ventricles (LV).s%‘* However, a minority had high PAWP pulmonary oedema and an overloaded intravascular compartment. The CVP may represent a more accurate index of hypovolaemia but the ability of the LV to handle intravascular expansion may best be evaluated by measuring the PAWP.” One study showed a modest correlation between PAWP and CVP (r = 0.59). but Benedetti et al, demonstrated that the CVP frequently does not correlate with the PAWP when the CVP is over 6mmHg.l’ Clark and Cotton suggest that it is clinically impossible to detect those patients in which the left and right sided filling pressures do not correlate, and that the CVP is an unacceptable measure of pre-load in a patient with severe PET.19 They advocate either simple clinical management or the insertion of a PA catheter to obtain a valid assessment of LV pre-load. Their three main indications for PA catheterisation are resistant hypertension prior to aggressive afterload reduction, the presence of pulmonary oedema, and oliguria. Mabie et al however, consider that most patients may be managed without PA catheterisation, but include the induction of epidural anaesthesia and massive haemorrhage as indications for its use.8 Pulmonary oedema complicating PET is rare, but frequently associated with serious medical, surgical or obstetric complications.17 When present, the maternal and fetal morbidity and mortality is high, and these patients need aggresive monitoring and intervention. The management of patients with cardiogenic (high PAWP) and non-cardiogenic (low PAWP) forms of pulmonary oedema is different, and PA catheterisation would seem mandatory when pulmonary oedema exists to guide therapy. Over 60% of the patients who developed pulmonary oedema did so over 48 h after delivery, indicating the need for continued close observation of these patients post-natally. The balance of evidence would suggest that when the CVP is low the PAWP is unlikely to be raised. Oliguria may respond to initial fluid infusion, but if it does not, CVP monitoring should be instituted. If the CVP exceeds 6mmHg, or if pulmonary oedema is present, PA catheterisation is indicated. Additional useful information about cardiac output, and sys-

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temic or pulmonary vascular resistance may then be obtained to aid patient management.

Control of blood pressure

Controlled reduction of blood pressure is primarily required to reduce the cerebral complications of pre-eclamptic hypertension, and treatment is indicated when the pressures exceed 170/110mmHg.20 However, excessive hypotension potentially jeopardises placental perfusion, the control of which is presently poorly understood. Since the maternal circulation is a high vascular resistance, low plasma volume state, there is a significant risk of severe hypotension on initiating therapy. Wasserstrum et al advocate fluid loading prior to vasodilator therapy to minimise this haemodynamic instability.’ Intravenous hydralazine, by bolus or infusion, presently forms the mainstay of acute treatment in most units, tachycardias frequently although undesirable develop. Newer agents include nifedipine which is convenient to use and effective. Early results suggest that it is safe in pregnancy, although interactions may occur with other negatively inotropic agent.*’ Labetolol avoids reflex maternal tachycardias, and has no bradycardic or hypotensive effects on the fetus.*l It is rapid in onset, and effective in most patients, although further investigation into the dose regimen and overall safety are required. Captopril has been shown to cause high fetal mortality in animal experiments and Redman considers it to be contraindicated in clinical use. *’ Magnesium sul p hate is not currently popular in the UK and is discussed under eclampsia.

Coagulopathy

A variety of disorders of coagulation have been seen in PET, the most common being a low platelet count and prolongation of the thrombin time. This may be the result of a low-grade, subclinical disseminated intravascular coagulopathy (DIC) which may persist or progress rapidly. Fibrin D-dimer analysis has been proposed as a more sensitive and early indicator of intravascular coagulation and fibrinolysis than standard coagulation tests. ** These workers also postulated that the presence of the D-dimer may help identify the ‘severe’ pre-eclamptic patient at an early stage.

HELLP

syndrome

The association of haemolysis, elevated liver enzymes and low platelets in PET is commonly labelled the HELLP syndrome. However, there has been no consistency in the terminology or diagnostic criteria used to describe this syndrome, and in his review Sibai calls for standardisation.23 Although

commonly diagnosed in hypertensive, proteinuric patients, it has also been seen in patients without these features and patients may present with a variety of symptoms, most commonly malaise, nausea and vomiting or upper adominal pain.24 The morbidity associated with HELLP is high, and includes hepatic rupture, acute renal failure, DIC and abruption. 25 The consequences for the fetus are also serious, and in one study the perinatal mortality reached 367 per 1000. 25 Early sub-clinical cases may be detected by simple blood tests, and a low threshold of suspicion in all pre-eclamptic patients should be maintained. Eclampsia

The effective management of eclampsia requires control of convulsions, blood pressure and airway, where appropriate, and early delivery of the fetus. Magnesium sulphate has been the mainstay of treatment for convulsions in North America for many years, but has not become popular in Europe, where more specific anti-convulsant and anti-hypertensive agents are preferred. Diazepam is generally accepted as the drug of choice in the acute situation, but there is much debate regarding the best prophylactic regimen. Current practice in the UK is to use intravenous diazepam or chlormethiazole infusions to maintain anticonvulsant therapy.*’ However, both these drugs may produce excessive sedation and respiratory depression in mother and baby. Excessive sedation contributed to the deaths of three patients from respiratory arrest in the last triennium.’ For these reasons there is increasing interest in the use of other anti-convulsants such as intravenous phenytoin. It is rather difficult to give, requiring a relatively large loading dose usually in excess of 1 gram, and may cause cardiac arrythmias, hypotension or pain on injection, but does not leave the patient sedated. There is great need for large randomised multicentre studies to evaluate magnesium sulphate and other alternatives. To date, there appear to have been only two comparative studies published. Crowther, in could demonstrate no significant Zimbabwe, difference between treating eclampsia with magnesium sulphate or diazepam in terms of morbidity or recurrent fits. 26 In a study of 22 patients, Dommisse in South Africa suggested that phenytoin is a less effective anticonvulsant in eclampsia than magnesium sulphate and four out of eleven patients had further seizures after starting phenytoin.27 Unfortunately, since both these studies were performed at tertiary referral centres, the majority of patients had already received some treatment prior to entering the studies, which may confuse the results. Ryan et al in Canada used four different regimes of phenytoin as prophylaxis in severe pre-eclampsia, and found that in appropriate dosage, therapeutic levels were rapidly achieved with minimal side effects and no subsequent seizures.28

PRE-ECLAMPSIA,

Critics of magnesium sulphate cite the 10% incidence of breakthrough convulsions on treatment, the fact that it has never been shown to be an effective anti-convulsant, the widely varying dose recommendations, the need for regular plasma magnesium analyses, its toxicity at high plasma levels, and the interactions with muscle relaxants, as cogent reasons to avoid its use in eclampsia.29 However, careful comparative evaluation of magnesium sulphate needs to be made, since it may well yet prove to be better than anything else that is available in the UK.

Choice of anaesthesia In a contentious article in the New England Journal of Medicine, Lindheimer and Katz claim ‘Epidural block should be avoided since in pre-eclampsia it is associated with sudden and marked falls in blood pressure and on occasions with vascular collapse’.30 This statement prompted Gutsche to collect opinions from several eminent anesthesiologists and obstetricians, and the resultant correspondence demonconfidence in epidural strated considerable anaesthesia.31 Indeed, Shnider et al demonstrated a fall in maternal adrenaline levels after the establishment of epidural blockade,32 and Jouppila showed there to be increased mean intervillous blood flow under well controlled epidural anaesthesia in PET.33 There appears to be little disagreement that epidural modern anaesthetists amongst anaesthesia is the technique of choice for labour or Caesarean section in PET, wherever possible. However, where eclamptic convulsions are considered likely a general anaesthetic is indicated, since the consequences of a convulsing patient during an epidural Caesarean section could be disastrous. In view of the severe and rapid haemodynamic changes which may be precipitated by spinal anaesthesia, this technique is not generally considered appropriate in pre-eclampsia or eclampsia. Epidural anaesthesia

The use of adrenaline containing solutions is controversial, and there is a strong body of opinion that they should not be used in the pre-eclamptic patient owing to the perceived increased risk of placental hypoperfusion. The evidence for this occurring, however, is not extensive, but there would seem to be little real advantage in using an adrenaline-containing solution in pre-eclampsia, a controversial enough question in normal parturients! Ramanathan et al showed that the clearance of epidural lignocaine is reduced in pre-eclamptic women, and consider it to be a result of alterations in hepatic blood flow, hepatocellular function and protein binding.34 Similar effects are likely with other amide local anaesthetic agents. An increasing number of patients are presenting to the anaesthetist on low-dose aspirin therapy. The

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effect on maternal haemostasis produced is usually insignificant, but occasionally may be unexpectedly pronounced. Thus a counsel of caution would advocate performing a platelet count, or preferably a bleeding time (a good in-vivo test of platelet function), prior to epidural anaesthesia. There are, as yet, no clear guidelines for acceptable safe limits, but a level of platelets > 100000 mmp3 or a bleeding time cl0 min is commonly used. Although the bleeding time correlates well with the platelet count when
Careful control of blood pressure is required to avoid excessive hypotension, or more commonly, a severe rise in blood pressure which may occur as a response to laryngoscopy, surgery or extubation. Sudden rises in blood pressure may increase the risks of cerebral haemorrhage and oedema, cardiac failure, myocardial infarction or pulmonary oedema. However, in spite of the potential problem, there have been few reports of laryngoscopy-related hypertensive sequelae in the literature, and it is unclear how great is the actual risk. Many different techniques have been proposed over the years to attenuate the hypertensive response to laryngoscopy including hydralazine, trimetaphan, nitroprusside and nitroglycerine. Intravenous lignoCaine is a predominantly North American practice whose mode of action is unclear. Connell et al showed that in South African patients with severe PET or incipient eclampsia, a standard technique of IV lignocaine 1 mg. kg-‘, etomidate, suxamethonium, alcuronium and halothane given after trimetaphan and practolol resulted in a mean systolic blood pressure rise of 56mmHg.36 Better results were achieved in the majority of patients by Lawes et al from the same establishment, when fentanyl and droperidol were added to a similar regime, although five out of 24 patients still showed an unmodified response to laryngoscopy with rises in systolic pressure between 40-70mmHg.37 The control of blood pressure at the end of the procedure on extubation was also considered unsatisfactory by the authors. In a group of mild to moderate pre-eclamptic patients, Ramanathan et al demonstrated labetolol lmg.kg-’ to have some effect on attenuating the pressor response to laryngoscopy with no maternal or

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AND CRITICAL CARE

fetal side-effects.38 Further studies in patients with more severe disease and possibly larger drug dosages are required. Alfentanil O.Olmg.kg-’ has been used successfully to modify the cardiovascular response to intubation, at the cost of increased post-operative nausea and potential neonatal depression.39 A recent study from South Africa suggests fentanyl to be an effective alternative to alfentanil.40 Although there is, as yet, no clear answer to the problem, a potent intravenous opioid prior to induction may be the technique of choice, although naloxone may be necessary for the neonate. Post operative care Although delivery of the placenta is the sole curative manoeuvre, it must not be forgotten that the postoperative period is crucial in the safe management of these patients. PET is associated with a number of serious, life-threatening conditions which may all present for the first time in the puerperium. The overall condition of the patient often worsens for 3 or 4 days post-partum, and convulsions, hypertension, haemorrhage and cardiac decompensation may all occur in this period. Sibai et al showed that 60% of patients who developed pulmonary oedema did so more than 48h post-partum.17 Hence continued therapy and close monitoring are required for several days in the severe pre-eclamptic patient.

Conclusions Pre-eclampsia is a common condition which may progress to a severe multi-system disorder, and which, when established, is frequently fatal to mother and baby. It is asymptomatic for the majority of its course, and hence all patients require careful antenatal screening to allow early diagnosis and treatment. Once symptoms develop, hepatic dysfunction, coagulopathy and fulminent eclampsia may rapidly ensue. Whilst the majority of patients require minimal intervention, the severe pre-eclamptic patient needs expert care with access to invasive monitoring and therapy in an intensive care situation. Ultimately, the successful management of these patients is dependent on the teamwork and communication of the obstetrician, midwife and anaesthetist, all of whom have important roles to play.

1. Report on confidential enquiries into maternal deaths in England and Wales 198284. HMSO 1989; 34 2. Sibai BM. Pitfalls in diagnosis and management of preeclampsia. Am J Obstetand Gynecol 1988; 159: l-5 3. Redman CWG. Jefferies M. Revised definition of ureeclampsia. Lancet 1988; April 9: 809-812 4. Brown MA. Pregnancy-induced hypertension: Current concepts. Anaesth Intens Care 1989; 17: 18.5-197 5. Cunningham FG, Gant NF. Prevention of pre-eclampsia - a reality? N Engl J Med 1989; 321: 606-607

6. O’Brien WF. Predicting pre-eclampsia. Obstet Gynecol 1990; 75,3: 445-452 7. Redman CWG, Beilin LJ, Bonnar J, Wilkinson RH. Plasmaurate measurements in predicting fetal death in hypertensive pregnancy. Lancet 1976; June 26: 1370-1373 8. Mabie WC, Ratts TE, Sibai BM. The central hemodynamics of severe pre-eclampsia. Am J Obstet Gynecoll989; 161: 1443-1448 9. Wasserstrum N, Kirshon B, Willis RS, Moise KJ, Cotton DB. Quantitative hemodynamic effects of acute volume expansion in severe pre-edampsia. Obstet Gynecoll989; 73: 546-550 10. Belfort M, Uys P, Dommisse J, Davey DA. Haemodynamic changes in gestational proteinuric hypertension: the effects of rapid volume expansion and vasodilator therapy. Br J Obstet Gynaecol 1989; 96: 634641 11. Ramanathan S. Pre-eclampsia. In: Ramanathan S. Obstetric Anesthesia. Philadelphia: Lea and Febiger 1988; 151-166 12. Benedetti TJ, Kates R, Williams V. Hemodynamic observations in severe pre-eclampsia complicated by pulmonary oedema. Am J Obstet Gynecol 1985; 152: 330-334 13. Jouppila P, Jouppila R, Koivula A. Albumin infusion does not alter the intervillous blood flow in severe pre-eclampsia. Acta Obstet Gynecol Stand 1983; 62: 345-348 14. Cotton DB. Haemodynamic management of pregnancyinduced hypertension. Personal presentation at: ACOG Postgraduate course, San Francisco, 3rd June 1988 15. Clark SL, Greenspoon JS, Aldahl D, Phelan JP. Severe pre-eclampsia with persistent oliguria: Management of hemodynamic subsets. Am J Obstet Gynecoi 1986; 154: 490-494 16. Kirshon B, Lee W, Mauer MB, Cotton DB. Effects of low-dose dopamine therapy in the oliguric patient with preeclampsia. Am J Obstet Gynecol 1988; 159: 604-607 17. Sibai BM, Mabie WC, Harvey CJ, Gonzalez AR. Pulmonary edema in severe pre-eclampsia-eclampsia: Analysis of thirtyseven consecutive cases. Am J Obstet Gynecol 1987; 156: 1174-1179 18. Cotton DB, Lee W, Huhta JC, Dorman KF. Hemodynamic profile of severe pregnancy-induced hypertension. Am J Obstet Gynecol 1988; 158: 523-529 19. Clark SL, Cotton DB. Clinical indications for pulmonary artery catheterization in the patient with severe preeclampsia. Am J Obstet Gynecol 1988; 158: 453-458 20. Redman CWG. Hypertension in pregnancy. In: de Swiet, ed. Medical Disorders in Obstetric Practice. Blackwell Scientific Publications 1989; 249-305 21. Mabie WC, Gonzalez AR, Sibai BM, Amon E. A comparative trial of labetolol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol 1987; 70: 328-333 22. Trofatter KF, Howell ML, Greenberg CS, Hage ML. Use of the fibrin D-dimer in screening for coagulation abnormalities in pre-eclampsia. Obstet Gynecol 1989; 73, 3: 435-439 23. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): Much ado about nothing? Am J Obstet Gynecol 1990; 162: 31 l-316 24. Aarnoudse JG. Houthoff HJ. Weits J. Vellenea E. Huisies HJ. A syndrome of liver damage and intravas&lar’ * coagulation in the last trimester of normotensive pregnancy. A clinical and histopathological study. Br J Obstet Gynaecol 1986; 93: 145-155 25. Sibai BM, Taslimi MM, El-Nazer A, Amon E, Mabie WC, Ryan GM. Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe pre-eclampsia-eclampsia. Am J Obstet Gynecol 1986; 155: 501-509 26. Crowther C. Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial. Br J Obstet Gynaecol 1990; 97: 110-117 27. Dommisse J. Phenytoin sodium and magnesium sulphate in the management of eclampsia. Br J Obstet Gynaecol 1990; 97: 104-109 28. Ryan G, Lange IR, Naugler MA. Clinical experience with phenytoin prophylaxis in severe pre-eclampsia. Am J Obstet Gynecol 1989; 161: 1297-1304 29. Kaplan PW, Fisher RS. Does magnesium sulfate treat eclamptic seizures? Arch Neural 1988; 45: 1361-1364 30. Lindheimer MD, Katz AL, Current concepts: Hypertension in pregnancy. N Engl J Med 1985; 313: 675-680

PRE-ECLAMPSIA, 31. Gutsche B. The experts opine: is epidurai block for labor and delivery and for Cesareau section a safe form of analgesia in severe pre-eclampsia or eclampsia? Surv Anesthes 1986; 30: 304-311 32. Shnider SM, Abboud TK, Artal R, Henriksen EH, Stefani SJ, Levinson G. Maternal catecholamines decrease during labour after epidural anesthesia. Am J Obstet Gynecol 1983; 147: 13-15 33. Jouppila P, Jouppila R, Hollmen A, Koivula A. Lumbar epidural analgesia to improve intervillous blood flow during labor in severe pre-eclampsia. Obstet Gynecol 1982; 59: 158-161 34. Ramanathan R, Bottorff M, Jeter JN, Khalil M, Sibai BM. The pharmacokinetics and maternal and neonatal effects of epidural lidocaine in pre-eclampsia. Anesth Analg 1986; 65: 120-126 35. Ramanathan J, Sibai BM, Vu T, Chauhan D. Correlation between bleeding times and platelet counts in women with pre-eclampsia undergoing Cesarean section. Anesthesiol 1989; 71: 188-191

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36. Connell H, Dafgleish JG, Downing JW. General anaesthesia in mothers with severe pre-eclampsia/echunpsia. Br J Anaesth 1987; 59: 1375-1380 37. Lawes EG, Downing JW, Duncan PW, Bland B, Lavies N, Gane GAC. Fentanyl-droperidol supplementation of rapid sequence induction in the presence of severe pregnancyinduced and pregnancy aggravated hypertension. Br J Anaesth 1987; 59: 1381-1391 38. Ramanathan J, Sibai BM, Mabie WC, Chauhan D, Ruiz AG. The use of labetolol for attenuation of the hypertensive response to endotracheal intubation in pre-eclampsia. Am J Obstet Gynecol 1988; 159: 650-654 39. Dann WL, Hutchinson A, Cartwright DP. Maternal and neonatal responses to alfentanil administered before induction of general anaesthesia for Caesarean section. Br J Anaesth 1987; 59: 1392-1396 40. Rout CC, Rocke DA. Effects of alfentanil and fentanyl on induction of anaesthesia in patients with severe pregnancyinduced hypertension. Br J Anaesth, 1990; 65: 468-474