Hypertension in pregnancy is diagnosed either by raised absolute values of systolic or diastolic pressure (> 140 mmHg and > 90 mmHg respectively) or by increases in systolic or diastolic pressures above those at booking (> 30 mmHg and > 15 mmHg respectively). Pressures should be raised on two separate occasions using appropriate methods of measurement (see below).
Hypertensive disorders of pregnancy are divided into chronic hypertension, gestational hypertension and pre-eclampsia.
Chronic hypertension and gestational hypertension
Chronic hypertension occurs in 3-5% of pregnancies, though the incidence is increasing in the UK as maternal age increases. It is diagnosed by pre-existing hypertension, hypertension that occurs before 20 weeks’ gestation (although the diagnosis may be masked by the normal slight fall in blood pressure that occurs in early pregnancy, and pre-eclampsia may rarely present earlier than 20 weeks), or hypertension that develops in pregnancy and persists postpartum. The risk of pre-eclampsia is approximately doubled, and there is also a greater risk of abruption and fetal growth restriction, but if the blood pressure is controlled, women with chronic hypertension would be expected to have good outcomes.
Gestational hypertension describes hypertension after 20 weeks’ gestation without any features of pre-eclampsia, and occurs in 6-7% of pregnancies. The risk of pre-eclampsia is increased slightly, this risk increasing the earlier the hypertension develops. Blood pressure usually returns to normal within 1-2 months of delivery.
Pre-eclampsia
Pre-eclampsia is now defined as hypertension that develops after 20 weeks’ gestation in a previously normotensive woman, that is associated with proteinuria or impairment of one or more organ system. This may include renal, hepatic, respiratory, neurological, haematological or uteroplacental disease. Because of practical difficulties in quantifying 24-hour proteinuria, measurement of a random urine protein/creatinine ratio (PCR) is often done instead, a PCR above 30 mg/mmol correlating with a 24-hour protein excretion greater than 300 mg. It is possible to develop non-proteinuric pre-eclampsia, and also to have eclamptic seizures with minimal or even no hypertension. Pre-eclampsia occurs in 5-6% of pregnancies overall (up to 25% in patients with pre-existing hypertension).
Pre-eclampsia/eclampsia is a major cause of direct maternal death worldwide. The pathophysiology of pre-eclampsia is still only partially understood, but it is known that failure of placentation occurs early in pregnancy and this leads to vascular endothelial cell damage and dysfunction. The endothelial cell damage is thought to lead to release of vasoactive substances, which promote generalised vasoconstriction and reduced organ perfusion. This is exacerbated by an increased sensitivity to circulating catecholamines. Preeclamptic women demonstrate an imbalance of the normal thromboxane/prostacyclin ratio and increased free radical activity.
Pre-eclampsia encompasses HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome, eclampsia and possibly acute fatty liver of pregnancy. Although the disease is progressive, a mother may be asymptomatic until she presents with an eclamptic fit, and although pre-eclampsia is a disease of pregnancy, terminated only by delivery, preeclampsia, HELLP syndrome and eclampsia may all present for the first time after delivery.
There have been many attempts to prevent development of pre-eclampsia, for example with dietary vitamins, antioxidants and minerals, with no clear benefit found. There is evidence that low-dose aspirin may be beneficial in selected high-risk women.
Problems and special considerations
Blood pressure measurements should be made with the mother sitting (or on her side in late pregnancy) to avoid aortocaval compression. Most automated blood pressure measuring devices have not been validated in pregnancy, and many tend to under-read blood pressure, especially in pre-eclampsia, giving a false sense of security (though they can be used to monitor trends, so long as manual measurements are taken at intervals). If manual methods of measurement are used, it is now recommended that Korotkoff phase V sounds should be used to measure diastolic pressure, not phase IV, since the former are more reproducible and better correlated with true diastolic pressure in pregnancy.
Pre-eclampsia is frequently asymptomatic despite significant disease. Symptoms are often non-specific and include headache (commonly frontal), visual disturbance and epigastric or right upper quadrant pain. The most commonly occurring signs are hypertension, oedema and hyperreflexia, although the last of these is subjective and unreliable as a prognostic indicator (though sustained clonus is pathological). Severe pre-eclampsia is characterised by features of significant end-organ dysfunction that may include pulmonary oedema, cerebral haemorrhage, elevated transaminases (doubling of the normal level or ALT > 70 IU/L), renal dysfunction (proteinuria > 5 g/24 h, 3+ protein dipstick or doubling of serum creatinine in the absence of other pathology) or coagulopathy, e.g. thrombocytopenia, haemolytic anaemia or DIC. Oedema may also affect the airway, and pleural and pericardial effusions may occur. Occasionally the clinical presentation may be dramatic - ruptured liver has been reported.
Chronic impairment of uteroplacental blood flow causes fetal growth restriction, and this maybe one of the first signs of pre-eclampsia. There is an increased risk of prematurity. Placental abruption may occur in severe disease.
The normal expansion of blood volume that takes place in early pregnancy fails to occur in pre-eclamptic women, and there is therefore a relatively hypovolaemic state. This is exacerbated by leaky capillaries, which allow inappropriate fluid shifts between compartments. Colloid osmotic pressure is low in women with pre-eclampsia, and any increased hydrostatic pressure due to iatrogenic fluid overload, impaired left ventricular function or postpartum fluid shifts may therefore readily precipitate pulmonary oedema.
Results of the numerous studies (both invasive and non-invasive) of the haemodynamic changes occurring in pre-eclampsia are confusing. There is generalised vasoconstriction and therefore systemic vascular resistance is usually increased. Cardiac index and cardiac output may be high, low or normal but this is frequently a reflection of drug therapy. In severe pre-eclampsia, especially if there is pulmonary oedema, right atrial pressure may not accurately reflect pulmonary artery pressure, and central venous pressure monitoring may therefore be an unreliable guide to treatment.
In the UK, approximately 1-2% of pre-eclamptic women develop eclampsia (~2—3 per 10,000 births), though the incidence is higher in the developing countries. Forty per cent of eclamptic fits occur after delivery, most commonly within the first 3 days and rarely more than 1 week postpartum. In approximately a third of cases, there are minimal prodromal signs or symptoms, and only ~40% have proteinuria or hypertension in the preceding week. Recurrent seizures are associated with increased maternal morbidity and mortality. Twenty per cent of eclamptic patients experience pre-eclampsia in the next pregnancy, and 2% have eclampsia.
Posterior reversible encephalopathy syndrome (PRES) is a particular complication that is not specific to pregnancy or to pre-eclampsia, but is increasingly described in association with the latter. Clinical features include headache, convulsions, confusion and visual loss. Several mechanisms for PRES have been hypothesised; it is thought to be a manifestation of cerebral oedema caused either by impaired cerebral autoregulation with accelerated hypertension, or by cerebral vasospasm that results in reduced cerebral blood flow and cytotoxicity. Magnetic resonance imaging (MRI) is the gold standard for diagnosis and follow-up and should be obtained ideally 1—2 days after the initial event. T2-weighted imaging typically reveals bilateral hyperintensities, predominantly in the parieto-occipital region. Magnesium sulfate is the first line of treatment and may be used concomitantly with antihypertensive therapy. Recovery usually takes several days, though neurological deficits may persist.
Management options
The management of chronic and gestational hypertension consists of antihypertensive drugs and close monitoring for development of pre-eclampsia or fetal growth restriction.
The reports of the Confidential Enquiries into Maternal Deaths (CEMD) strongly recommend that every obstetric unit should have written guidelines for the management of pre-eclampsia and eclampsia. There have also been recommendations that every obstetric unit should have an ‘eclampsia pack’ containing everything necessary to treat eclamptic women with magnesium.
Women who do not present with severe features or major fetal compromise are usually offered a trial of vaginal delivery, while those with severe pre-eclampsia (especially < 37 weeks’ gestation) are likely to be delivered by caesarean section (although some evidence exists to support expectant care). The anaesthetist should assess the mother, paying particular attention to any symptoms of pre-eclampsia, drug treatment, the airway, the level of hypertension, the results of haematological and biochemical investigations, and the proposed mode of delivery.
Hypertension
Treatment of hypertension does not modify the course of the underlying disease process but may reduce the morbidity and mortality attributable to uncontrolled hypertension. Whether treatment of mild hypertension during pregnancy is worthwhile is unclear, but because of the risk of haemorrhagic stroke most guidelines suggest treating a systolic blood pressure of 160 mmHg or more. The first-line treatment of hypertension includes methyldopa, which has a long safety record for the fetus, labetalol, nifedipine and other β- adrenoreceptor blockers such as metoprolol and propranolol. Patients already receiving angiotensin-converting enzyme inhibitors or anti-angiotensin receptor agents should have them withdrawn because of their fetotoxic effects.
Hydralazine is the most commonly used agent for management of acute hypertension. Administration of small repeated intravenous boluses (e.g. 5 mg) is preferable to continuous infusion. Hydralazine acts primarily as a vasodilator and should therefore be used with caution and preferably in conjunction with gentle volume replacement, since acute vasodilatation may cause an uncontrolled fall in blood pressure and thus provoke fetal distress. (Reduction in maternal blood pressure is associated with a significantly greater percentage reduction in uteroplacental perfusion.)
Labetalol (10 mg boluses) may be used parenterally in the acute situation, and oral nifedipine (5-10 mg) has also been used, acting within 15-30 minutes. Although there have been concerns over sublingual nifedipine and the risk of uncontrolled hypotension, particularly in combination with magnesium sulfate, this is not thought to be a common problem, especially with slow-release preparations.
Nitroprusside and glyceryl trinitrate may be used for acute control of hypertension but are not commonly used in the UK.
Angiotensin-converting enzyme inhibitors are contraindicated in pre-eclampsia, as their use is associated with unacceptably high fetal morbidity and mortality.
Convulsions
Magnesium sulfate has been shown to reduce the incidence of eclampsia in pre-eclampsia by approximately half, although whether it should be offered routinely to women with preeclampsia is controversial, since only 1-2% of them go on to develop eclampsia in the UK, and a significant proportion of eclamptics cannot be identified beforehand (see Chapter 87, Magnesium sulfate).
In women who have had a convulsion, magnesium sulfate reduces the incidence of recurrent convulsions by about half compared with phenytoin and diazepam, and ‘magnesium packs’ should be available on every labour ward.
The optimum treatment of convulsions themselves is less clear. Both magnesium sulfate and diazepam have been used, though some authorities claim that eclamptic fits are self-limiting and that no treatment other than initiation of the magnesium sulfate regimen is needed.
Analgesia for labour
Regional analgesia is the method of choice, since it prevents hypertensive episodes associated with contraction pain and may be beneficial to the compromised fetus by improving uteroplacental perfusion. Although epidural analgesia may lower blood pressure, it should not be considered a treatment for hypertension. A combination of low-dose local anaesthetic and opioid may be given by continuous epidural infusion or intermittent boluses, and this can be supplemented as necessary should instrumental or operative delivery be required.
The platelet count should be measured before insertion of the epidural (if trends suggest that platelet numbers are decreasing significantly, a platelet count should be repeated immediately before epidural insertion; otherwise, a platelet count within the last ~4 hours is usually considered adequate). Current opinion suggests that a platelet count of at least 75 x 109/1 is advisable before instituting central neural blockade, although any stated lower safe limit is entirely arbitrary, and the relative risks and benefits of regional analgesia and anaesthesia must be considered for each patient. Several studies have confirmed that if the platelet count is at least 100 x 109/l there is no need to perform further coagulation studies. In some centres, thromboelastography/thromboelastometry or similar techniques are used to assist decision making concerning epidural insertion.
If epidural analgesia is contraindicated, it is important to control the blood pressure by using appropriate agents (hydralazine, nifedipine, labetalol) and to provide alternative analgesia. Patient-controlled intravenous opioids offer the mother the psychological benefit of being in control of her analgesia and are more predictable than intramuscular opioids.
Anaesthesia for caesarean section
Regional anaesthesia
Regional is preferable to general anaesthesia, both for the mother and for the fetus. Although the use of spinal anaesthesia in pre-eclampsia was traditionally avoided because of the fear of causing severe hypotension, there is now evidence that so long as there is no hypovolaemia, cardiovascular stability is maintained better in pre-eclamptic patients than in non-pre-eclamptic ones. Furthermore, there is evidence that uterine artery velocity and neonatal condition are unaffected by spinal anaesthesia if systolic arterial pressure remains at least 80% of baseline.
Combined spinal-epidural anaesthesia confers the benefits of dense anaesthesia (especially of the sacral nerve roots) with the flexibility of epidural anaesthesia and postoperative analgesia.
The untreated pre-eclamptic mother may exhibit greater sensitivity to vasoconstrictors than the normotensive mother. Adrenaline-containing epidural solutions are sometimes avoided in severe cases, although their use appears to be safe.
General anaesthesia
General anaesthesia may be necessary if there is great urgency to deliver the mother or if regional anaesthesia is contraindicated by coagulopathy or major haemorrhage. Extreme prematurity does not contraindicate regional anaesthesia, and nor does eclampsia.
The additional risks of general anaesthesia for caesarean section (see Chapter 36) are compounded in the pre-eclamptic woman by the potential for a significantly compromised airway and the hypertensive response to intubation and extubation. There may also be potential drug interactions, especially between magnesium sulfate and neuromuscular blocking agents.
Laryngeal oedema is uncommon but may be sufficient to obscure all normal anatomy at laryngoscopy. Each obstetric theatre should include small-sized tracheal tubes on the intubation trolley for this eventuality.
Uncontrolled hypertension in response to tracheal intubation may provoke cardiac arrhythmias, myocardial ischaemia or cerebrovascular catastrophe. Numerous agents have been used to attenuate this response, but the most commonly used agents in the UK are fentanyl 1-4 μg/kg or alfentanil 7-10 μg/kg and labetalol 10-20 mg. Other opioids, β- blockers and lidocaine may be used; magnesium sulfate 30 mg/kg also appears to be effective.
Monitoring and fluid therapy
All women with moderate or severe pre-eclampsia should have continuous electronic fetal monitoring. Direct arterial pressure monitoring is more accurate than non-invasive methods, because of the inaccuracy of most non-invasive monitors. The relative benefits of intraarterial monitoring must be balanced against the familiarity of midwifery staff with its use. Central venous pressure catheters may provide guidance for fluid administration during regional anaesthesia, although their use is uncommon in the UK. Access via the antecubital fossa rather than via neck veins is sometimes recommended, especially in the undelivered mother. Pulmonary artery catheterisation is rarely used. Transthoracic echocardiography has an increasing role in the assessment of volume status and ventricular function in patients with severe disease.
All pre-eclamptic women should have a urinary catheter inserted and an accurate hourly fluid balance recorded. Fluid management is controversial. The risks of volume overload and iatrogenic pulmonary oedema must be balanced against the risk of hypotension if vasodilators are given without concomitant volume replacement. In general, the emphasis has shifted away from liberal use of fluids in order to encourage urine output, towards careful restriction, since long-term problems from renal failure are rare, whereas deaths from pulmonary oedema are well reported.
Postoperative management
In both HELLP syndrome and eclampsia, the risks of deterioration in blood pressure control do not end immediately with delivery of the placenta. Women with pre-eclampsia with severe features should be monitored in a high-dependency environment for at least 24-48 hours after delivery. Invasive monitoring and antihypertensive treatment should be continued during this time.
Key points
• Hypertensive disorders of pregnancy are divided into chronic hypertension, gestational hypertension and pre-eclampsia.
• Pre-eclampsia and eclampsia are major causes of maternal death.
• Although the classic presentation of the disease is hypertension and proteinuria occurring after 20 weeks of pregnancy, pre-eclampsia is a multisystem disease and may present atypically.
• HELLP syndrome is part of the spectrum of pre-eclampsia and may not be preceded by significant pre-eclampsia.
• Pre-eclampsia can only be effectively treated by delivery of the placenta, although symptomatic treatment attenuates maternal morbidity.
• Effective control of hypertension in pre-eclampsia reduces cardiovascular and cerebrovascular morbidity and mortality.
• Eclampsia may occur without premonitory symptoms or signs, and 40% of eclamptic fits occur after delivery.
Further reading
Dennis AT, Castro JM. Hypertension and haemodynamics in pregnant women: is a unified theory for pre-eclampsia possible? Anaesthesia 2014; 69: 1183-9.
Hofmeyr R, Matjila M, Dyer R. Preeclampsia in 2017: obstetric and anaesthesia management. Best Pract Res Clin Anaesthesiol 2017; 31: 125-38.
Leffert LR. What’s new in obstetric anesthesia? Focus on preeclampsia. Int J Obstet Anesth 2015; 24: 264-71.
Mol BWJ, Roberts CT, Thangaratinam S, et al. Pre-eclampsia. Lancet 2016; 387: 999-1011.
National Institute for Health and Care Excellence. Hypertension in Pregnancy: Diagnosis and Management. Clinical Guideline 107. London: NICE, 2010. www.nice.org.uk/guidance/CG107 (accessed December 2018).
Stocks G. Preeclampsia: pathophysiology, old and new strategies for management. Eur J Anaesthesiol 2014; 31: 183-9.