PET & eclampsia
Around the world, each year about half a million women die of pregnancy related causes. 99% of these occur in the developing world, usually of infection or haemorrhage, but in the developed countries, HT is the major preventable cause of fetal and maternal morbidity and mortality, affecting up to 5% of pregnancies. Worldwide, toxaemia accounts for about 10% of maternal deaths (Duley 1992), or 50 000 maternal deaths per year.
During pregnancy, generalised vasodilation and the large area of low-resistance shunt in the placental bed, result in increased cardiac output (40%) due to increased stroke volume. There are also increases in extracellular and blood volumes, renal blood flow, and glomerular filtration rate (50% at 16 weeks), and changes in renal tubular function. These are thought to be due to the effects of circulating prostaglandins. The net effect is a 10% decrease in BP in the first half of the pregnancy, with a gradual return to normal values by term. During labour, and continuing for a few days, BP can rise acutely due to increased preload with contractions, and pain and fear, with up to 12% of otherwise normal women having diastolic pressures exceeding 100mmHg. Also, 50 - 80% normotensive women are reported to have oedema at term.
Definition & Incidence
Pre-eclamptic toxaemia (PET) is defined as any two of three criteria:
BP>140/90 or an increase of 30/15 from baseline BP
proteinuria >1+, or >300mg / L over 24 hours
oedema
but may present as "HELP" (hepatic enzyme elevation & low platelets) syndrome, to indicate the other features that may occur in severe PET; including raised uric acid (>0.35mmol/L), CNS irritability, papilloedema and A-V nipping, poor urinary output, haemoconcentration, haemolysis, and coagulopathy.
PET will occur in 6% of first and 2% of subsequent pregnancies, especially if family history of PET, HT, or auto-immune disease. Risk also increased if multiple, large, or abnormal infants, maternal diabetes, or poor nutritional state of mother.
PET requires admission to an obstetric unit for close monitoring of mother and infant. The condition will often improve with bedrest, but if severe, and eclampsia seems imminent, urgent delivery is warranted regardless of gestation.
Eclampsia is fitting during or shortly after pregnancy. It may progress to status epilepticus, with cerebral oedema or haemorrhage, pulmonary oedema, cardiac failure, aspiration pneumonitis, liver and renal failure, and DIC. It is vital to realise that Eclampsia can occur without preceding signs, but that it is often preceded by:
- severe generalised headache
- visual disturbance eg. photophobia, blurred
- restlessness, agitation
- epigastric pain, nausea, vomiting
- hyper-reflexia and clonus
- altered level of consciousness, confusion
- rapid progression of PET
Prophylaxis:
Diuretics
12 randomised trials, 7000 women no clear evidence of benefit in progression of PET or perinatal death, no serious side effects reported
Antithrombotic and antiplatelet agents
Studies of asprin +/- dipyridamole are encouraging, but at this time do not substantially improve outcomes. Heparin is inconvenient, and increases bleeding complications, for no proven benefit
Dietary Measures
No evidence to support protein or calorie modification benefit
Calcium intake in excess of 2000mg daily is associated with a reduced risk of developing HT in pregnancy, insufficient evidence to support improved outcome as a result
No proven benefit in salt reduction or water restriction
Treatment of mild/mod. PET or HT
Bed rest
Socially costly and usually stressful, may be financially costly
2 controlled trials, with conflicting results
Elective confinement
1 small trial suggesting the outcomes for the mother are improved, but are worsened for the infant. No clear guidelines reached, although generally accepted to deliver at term.
Antihypertensives
Clearly reduce blood pressure, no effect on oedema or proteinuria, may slightly reduce risk of neonatal death.
Reduce the risk of hospital readmission and emergency delivery.
Methyldopa is the most widely used, onset 4 hrs. clonidine works similarly, but within 30 mins.
Beta-blockers reduce cardiac output, and may slightly increase the risk of IUGR.
Randomised trials of calcium channel blockers are so far too small to give useful estimates of their effects, as are studies of prostaglandin precursers.
Treatment of severe PET/Toxaemia
Antihypertensives
Hydrallazine most commonly used, then beta-blockers, and diazoxide less often.
Direct comparisons (nifedipine vs hydralazine, labetalol vs hydralazine, labetalol vs diazoxide, and prostacyclin vs dihydralazine) fail to show a clear preference.
Diazoxide may cause a rapid drop in arterial pressures & fetal hyperglycaemia, labetalol may cause fetal bradycardia
Plasma volume expanders
Non-crystalloid solutions (eg. dextran, albumin) have been used to restore the circulating plasma volume of severe PET. Uncontrolled trials suggest by doing so, other drug doses can be minimised, reducing side-effects. Insufficient data to reliably exclude an increased risk of cerebral or pulmonary oedema as a consequence.
Anti-convulsants
Librium and diazepam have been used since 1960s. Cheap, and readily available but are slowly metabolised by the infant, and apnoeas, hypotonia, poor sucking may last days. rate of infusion is titrated to maternal level of consciousness, so difficult to nurse.
Phenytoin is only recommended for prevention of convulsions, so used in conjunction with diazepam if required. most established infusion protocols rely on dose/weight, impractical in the acute setting. requires cardiac monitoring.
Magnesium first used in 1906 (intrathecally), the drug of choice in the USA (Consensus 1990). It can cause cardio-respiratory arrest, so close monitoring is needed, including serology, with calcium readily available as an antidote. Wide safety margin, cheap, with rapid onset. The Collaborative Eclampsia Trial (Lancet 1995), and Lucas et al (NEJM 1995) have compared MgSO4 to diazepam and/or phenytoin, and found significantly lower risks of recurrant seizures
(52% < diazepam,67%< phenytoin group) with a significantly lower risk of needing ICU +/- intubation, of developing pneumonia, or of infants needing SCU +/- intubation.
Motor vehicle accidents
Injuries are less severe if seat belts are worn, but are then usually lower abdominal trauma. Abruption can occur several hours after the impact, so if high speed MVA consider admitting for 48 hours fetal monitoring.
Diabetic coma
Ketoacidotic coma is rare in pregnancy and fetal outcome very poor. Hypoglycaemic collapse is more common and usually causes little fetal impact as insulin does not cross the placenta. Treat with IV or IM glucagon.
Sue Page is a general practioner obstetrician in Lennox Head, NSW, Australia