Pre-eclampsia
Pre-eclampsia is a multisystem disease, typically featuring hypertension and proteinuria occurring after 20 weeks’ gestation in a previously normotensive woman. It occurs in 5–8% of pregnancies.
It is caused by failure of placental implantation early in pregnancy, resulting in endothelial damage and dysfunction. This is thought to cause the release of vasoactive substances that promote vasoconstriction and organ hypoperfusion. Pre-eclamptic women also have increased sensitivity to circulating catecholamines and an imbalance in the thromboxane:prostacyclin ratio.
Pre-eclampsia can progress to HELLP (a syndrome encompassing haemolysis, elevated liver enzymes, and a low platelet count) and eclampsia. Eclampsia occurs in 1–2% of patients with pre-eclampsia in the UK, and it may be the first presentation of the condition. Forty per cent of eclamptic fits may occur post-delivery.
The only cure for pre-eclampsia is delivery of the fetus and placenta. As a consequence, pre-eclampsia is associated with prematurity of the neonate. However, the decision for delivery is for maternal indications. Treatment of hypertension does not alter the course of the underlying disease process, but it may reduce the morbidity and mortality caused by uncontrolled hypertension.
There is a significant risk of pre-eclampsia recurring in subsequent pregnancies (one in four if severe pre-eclampsia), and NICE have recommended the use of aspirin 75 mg daily from the 12th week of gestation until birth to reduce the recurrence.
1 Discuss the recognition and initial management of pregnancy-induced hypertension
2 Outline different anti-hypertensive therapies in the parturient
3 Discuss the operative management and post-operative care of the eclamptic patient.
2B02; 2B05
A 28-year-old primigravida presents at 27 + 5 weeks’ gestation, with hypertension (160/95 mmHg) and 3+ proteinuria. She is usually fit and well and has had an uncomplicated pregnancy thus far. She takes no medications, has no allergies, and is a non-smoker. Her BMI is 26, and airway examination does not indicate any potential difficulties. A BP profile done on the day assessment unit confirms her hypertension. She feels well and has no complaints on systemic enquiry.
The combination of hypertension and proteinuria is indicative of pre-eclampsia, risk factors for which include:
◆ Primigravida patients
◆ Family history of pre-eclampsia
◆ New partner
◆ Chronic hypertension
◆ Multiple pregnancy
◆ Previous pre-eclampsia
◆ Glucose intolerance and diabetes
◆ Obesity
◆ Molar pregnancy
◆ Antiphospholipid syndrome
◆ Cardiotocography (CTG): assessment of fetal well-being
◆ Departmental ultrasound scan (USS) to assess Doppler flow in the umbilical artery and to assess fetal growth. Pre-eclampsia is associated with intrauterine growth restriction (IUGR) and prematurity
◆ Blood samples:
• FBC: thrombocytopenia may be present
• Coagulation screen: disseminated intravascular coagulation (DIC) can occur
• Biochemistry: renal impairment may exist; elevated urate levels is a marker of pre-eclampsia; deranged liver function as a component of HELLP syndrome can occur
◆ Urine: proteinuria is defined as >0.3 g of protein in a 24-hour urine collection. Urinary Alb:Cr ratio ≥30 mg/mmol may be used also to predict for pre-eclampsia.
Absolute values of systolic pressure over 140 mmHg or diastolic pressure over 90 mmHg or an increase in BP by >30 mmHg, compared to booking BPs. The BP should be raised on two separate occasions before treatment is initiated. An isolated reading of diastolic BP >110 mmHg is also an indication to commence treatment.
◆ Labetalol
◆ Oral nifedipine
◆ Methyldopa
Her hypertension settles on treatment, and her blood results are normal, except for a urate of 0.41 mmol/L. She is discharged home but is readmitted at 28 + 6 weeks gestation, with a BP of 180/100 mmHg and 4+ proteinuria. She is now symptomatic, and biochemistry results demonstrate that her urate has now risen to 0.5 mmol/L. FBC shows Hb 102 g/L, WCC 12.4 × 109/L, Plt 113 × 109/L, down from a previous value of 247. Her urea is 5.6 mmol/L, and liver function tests (LFTs) and coagulation screen are normal.
◆ Cerebral: headache, visual disturbance, hyperreflexia, altered consciousness, clonus
◆ Respiratory: dyspnoea, cyanosis, pulmonary oedema, hoarseness
◆ Liver: epigastric, right upper quadrant pain/vomiting
◆ Renal: oliguria
◆ Generalized oedema
◆ Biochemistry: elevated urate, urea, creatinine
◆ Deranged LFTs
◆ Thrombocytopenia
◆ DIC
◆ Severe constant uterine pain, secondary to placenta abruption
She receives several doses of antihypertensive agents, but her BP remains elevated at 166/102 mmHg, although her symptoms seem to have improved.
◆ Labetalol infusion
◆ Hydralazine: this can be given IV as 5 mg boluses or initiated as an infusion. Hydralazine may cause a marked drop in BP, as the patient is often intravascularly volume-deplete. It may also cause tachycardia and cause the patient to feel tremulous.
The patient should ideally be managed in a high dependency setting, with an arterial line sited to monitor the efficacy of antihypertensive therapy and to facilitate frequent blood sampling. She should be catheterized, and hourly urine volumes should be documented. Typically, fluid intake is restricted to around 80 mL/hour to minimize the risk of pulmonary oedema developing. Neurological observations, including ankle reflexes for the development of clonus, should be monitored hourly. Regular ranitidine should be prescribed, and due consideration given as to the need to fast the patient in the event that emergency surgery is required. Regular blood tests, typically 6-hourly, should be taken, assessing for deterioration in renal function and possible further fall in platelets.
Fetal issues should be discussed with the neonatologist, including the optimal time of delivery and the administration of steroids for lung maturation, as necessary, to optimize the outcome of such a preterm infant. As the patient is likely to require imminent delivery, magnesium sulphate should be considered for neural protection of the fetus, as it is under 30 weeks’ gestation. This will also be useful in treating the mother, as she has severe pre-eclampsia.
Over the course of the next 12 hours, this lady starts to complain of severe frontal headache and abdominal pain. She appears jittery and agitated. Her BP is controlled at 148/96 mmHg. This woman has severe pre-eclampsia, and discussion around urgent delivery is required.
Magnesium sulphate, 4 g IV loading dose, should be administered over 15–20 min, then 1 g/hour for 24 hours from its commencement, as this has been demonstrated to reduce the incidence of eclampsia by 50%.
The decision is made to deliver this lady urgently by Caesarean section. Her most recent bloods show a further fall in her platelets to 64 × 109/L.
This case should involve a consultant anaesthetist due to the risks of haemorrhagic and neurological complications. In view of her platelet count, regional anaesthesia is relatively contraindicated, and therefore general anaesthesia is favoured.
◆ Anti-aspiration prophylaxis: IV ranitidine and oral sodium citrate
◆ Pre-oxygenate for 3 min
◆ Obtund pressor response to laryngocopy: opioid cover is commonly given during pre-oxygenation: either alfentanil 7–10 micrograms/kg bolus or remifentanil infusion with bolus of 1 microgram/kg. Other options are labetalol 10–20 mg, fentanyl 1–4 micrograms/kg, or magnesium sulphate 30 mg/kg
◆ RSI with thiopentone and suxamethonium
◆ Be prepared for potentially difficult intubation, due to laryngeal oedema, with smaller tracheal tubes, e.g. 6.0 and 6.5 mm, as well as the usual adjuncts for anticipated difficult intubation
◆ Consider a lower dose of a non-depolarizing neuromuscular blocker, as a patient who has had magnesium sulphate therapy has a prolonged action of muscle relaxants. A nerve stimulator should be used prior to reversal and waking the patient
◆ Uterotonics: IV Syntocinon® bolus 5–10 IU at delivery. Ergometrine is contraindicated, due to its hypertensive effects. An IV Syntocinon® infusion 40 IU over 4 hours, as there is a higher risk of haemorrhage in women with pre-eclampsia, exacerbated by co-existing thrombocytopenia
◆ Antibiotics should be given to the mother, following cord clamping, as she is at <32 weeks’ gestation
◆ A longer-acting opiate should be given for post-operative analgesia, following delivery of the fetus
◆ Fluid restrict: give the volume of fluid lost as a bolus, then maintain at 80 mL/hour
◆ TAP blocks are relatively contraindicated in view of thrombocytopenia
◆ Prior to extubation, you should assess for a leak around the tracheal tube, as laryngeal oedema may be considerable, necessitating the patient being admitted to intensive care for elective ventilation until this resolves.
Assuming the patient was extubated uneventfully, she should be ideally cared for in a high dependency setting. Antihypertensives should be continued, and magnesium sulphate should continue for a total of 24 hours from commencement. In the face of normotension, fluid restriction to 80 mL/hour should be continued, with hourly measurements of urine volumes.
A standard post-operative analgesic regimen includes regular paracetamol and morphine PCA. NSAIDs should be avoided, as these can cause renal dysfunction.
This should be managed initially with a fluid challenge of 250 mL of crystalloid. This should only be given once, as repeated boluses may precipitate pulmonary oedema. Colloid is avoided, as this may precipitate pulmonary oedema because the larger molecules pass into the pulmonary interstitial space.
A central venous catheter (CVC) should be inserted to guide subsequent fluid management. If the CVP is <4 mmHg, further 250 mL fluid boluses should be titrated in, until the CVP is in the 4–8 mmHg range; then subsequent urine output should be assessed. If the CVP is >8 mmHg, a single dose of furosemide should be considered.
Summary
Patients with pre-eclampsia benefit from regional anaesthesia for labour and delivery. Regional anaesthesia cannot be performed, however, if the platelet count is <80 × 109/L. If regional anaesthesia is possible, the dosage of drugs may need to be adjusted in relation to the gestation. The smaller the fetus, the less aortocaval compression, and the less subsequent compression of the cerebrospinal fluid (CSF) and epidural space. Larger local anaesthetic doses are therefore required to achieve adequate block height in earlier gestations. Vasopressors are less likely to be required and should be given in a lower dose than normal, as the patients are more sensitive to catecholamines (e.g. phenylephrine dose of 20 micrograms, compared to 40 micrograms in normal women).
Altman D, Carroli G, Duley L, et al. (2002). Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet, 359, 1877–90.
Anonymous (1995). Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet, 345, 1455–63.