Epidural therapy for severe pregnancy induced hypertension to reduce morbidity and mortality in the mother and infants

What is the issue?

Pre-eclampsia is a serious pregnancy-related, multiorgan disorder which effects both mother and baby generally in the third trimester. High blood pressure and protein in the urine are early indications of pre-eclampsia. If severe, women can develop headache, visual disturbance, pain in the stomach or upper abdomen regions, nausea and vomiting. They are at high risk of seizures, haemolysis (breakdown of red blood cells) elevated liver enzymes and low platelets (HELLP) syndrome, oedema in the lungs, widespread activation of blood clotting, loss of vision, renal or liver failure and placental abruption where the placenta separates from the uterus. The leakage of fluid out of the blood vessels and into the surrounding tissues causes swelling, reduced volume of circulating blood and blood flow to vital organs. The baby is at risk of restricted growth, stillbirth, preterm birth or death around the time of birth or soon after. The common cause appears to be a decrease in the blood flow to the uterus and placenta.

Why is this important?

Women with severe pre-eclampsia are treated with drugs to lower their blood pressure, magnesium sulphate or other anticonvulsants to prevent seizures (eclampsia), and drugs to control blood clotting.

Extended epidural anaesthesia may have a role in reducing the risk of stroke or cerebral bleeding, kidney and liver failure with severe pre-eclampsia. This could give time for optimal planning of delivery so that outcomes are improved for the mother and her baby. Blood flow to the uterus and placenta may be increased so that birth outcomes are improved. Extended epidural analgesia has also been reported to be well-tolerated for up to one week. The purpose of this review was to evaluate the use of epidural therapy as a treatment modality for severe pre-eclampsia and to compare this therapy with other established treatments.

What evidence did we find?

We searched for evidence in July 2017 and identified one small randomised controlled study (involving 24 women) for inclusion in this review. The women were at 30 weeks of gestation or more, diagnosed with severe pre-eclampsia, and being cared for in an intensive care unit. They were randomly assigned to an epidural block plus their other medications or a drug to treat their high blood pressure plus their other medications. After six hours of treatment they all underwent a caesarean section.

The included study did not report on any of the important outcomes of interest in this review such as death of the mother, death of her baby (before or after being born), serious illness for the mother or her baby, the mother developing eclampsia or seizures, or side effects of the intervention.

The study authors did report difference in the infant Apgar scores between the two groups The study authors also reported a clear drop in the diastolic blood pressure in the epidural group compared to the other group. Systolic and mean blood pressures were similar in the two groups of women. However, the study did not report on any other mother or baby outcomes of interest in this review.

What does this mean?

There is not enough evidence from randomised controlled trials to evaluate the use of epidural therapy in severe pre-eclampsia to improve outcomes for the mother or her baby. High-quality trials are needed to evaluate the efficacy, safety and cost of epidural therapy in severe pre-eclampsia. Future studies could report on important outcomes such as those listed in this review.

Authors' conclusions: 

Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women.

High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.

Read the full abstract...
Background: 

Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required.

Objectives: 

To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.

This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour.

Search strategy: 

We searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies.

Selection criteria: 

Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of these, were eligible for inclusion. Trials using a cluster design, and studies published in abstract form only are also eligible for inclusion in this review. Cross-over trials were not eligible for inclusion in this review.

Data collection and analysis: 

The two review authors independently assessed trials for inclusion and trial quality. There were no relevant data available for extraction.

Main results: 

We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding.

The included study did not report on any of this review's important outcomes. Meta-analysis was not possible.

For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema.

For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention.

Reported outcomes

The included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups.

The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups.

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