With preeclampsia affecting 10% of all pregnancies and rates rising by 25% in the past two decades, it is important to test your knowledge and ensure that all your patients have a strong understanding of the dangers of preeclampsia. This is part II of a two-part series. Part I focused on definitions, risks, prevention and diagnosis of preeclampsia; part II focuses on HELLP syndrome, treatment, eclampsia, future risk and resources.

The Preeclampsia Foundation reports that one in 12 pregnancies in the United States will be impacted by preeclampsia. Globally, preeclampsia is responsible for 76,000 maternal deaths and 500,000 infant deaths annually − approximately 5 deaths every hour. Preeclampsia needs to be recognized as a strong contributor to these statistics as maternal mortality rates continue to rise in the U.S. Preeclampsia is a leading cause of maternal morbidity and mortality and a major contributor of preterm birth. Consequences of preeclampsia include stroke, seizures, permanent organ damage, preterm birth, future cardiovascular disease, and maternal death. These outcomes highlight recognition and treatment failures within our healthcare system.

Preeclampsia is a disease unique to pregnancy and postpartum; it typically occurs after 20 weeks of pregnancy and impacts both mother and baby. Preeclampsia/eclampsia can occur up to 6 weeks postpartum, and it even impacts future maternal health and pregnancies. There are 100 serious non-fatal preeclamptic events for every preeclamptic-related death; hence, the seriousness of the disease cannot be overlooked. It is a progressive systemic vascular disease that impacts all organ systems. Previously, it was thought to be a blood pressure disease only occurring during pregnancy, cured by delivery of the baby, and requiring proteinuria for diagnosis; newer information highlights that it is not just a blood pressure disease, proteinuria is not required for diagnosing preeclampsia, and delivery of the baby does not resolve vascular damage and long-term sequelae. Early recognition, early intervention, and standardization of care for these patients does help to improve outcomes. 

Preeclampsia Treatment 

Standardized preeclampsia treatment has shown to improve maternal outcomes. Treatment takes into consideration maternal-fetal status; it becomes a balancing act regarding management and timing of delivery. Treatment considerations include: fetal status and gestational age, maternal status, labor status, severity of the disease, and availability of resources. Any patient experiencing blood pressure issues should have close monitoring and comprehensive maternal-fetal management. Antepartum testing should be initiated.

Newer recommendations suggest delivery at 37 weeks, which improves both maternal and fetal outcomes. Less favorable outcomes result from waiting for a favorable cervix and/or approaching 39 weeks and beyond. Diagnosis of preeclampsia does not require cesarean section for delivery; if mother and baby are stable, a trial of labor is appropriate. Induction of labor is attempted if there are no contraindications. Regional anesthesia is recommended at the time of delivery, as general anesthesia can be a risk for the patient with severe hypertension and preeclampsia. It is recommended to place the epidural early in the patient in the intrapartum setting so it will be ready and functional in case platelets continue to drop.

Preeclampsia without severe features may be managed at home when the patient is reliable. Ongoing outpatient testing of maternal-fetal status is acceptable. Women with barriers to follow-up and ongoing care should be hospitalized for observation. (Reminder: anti-hypertensives do not prevent evolution of the disease.)

The patient with severe features who is preterm is best managed in a tertiary care facility. MFM experts and a high-risk perinatal team will provide oversight of fetal surveillance and appropriate timing for delivery. Administration of antenatal corticosteroids should be given to all women with severe preeclampsia because of the strong possibility of preterm birth. Antenatal corticosteroid administration guidelines can be reviewed in the ACOG Committee Opinion Bulletin “Antenatal Corticosteroid Therapy for Fetal Maturation,” No. 677, October 2016.

Discretion is needed with preeclampsia that is superimposed on preexisting chronic hypertension because it leads to a worse prognosis. Also, be alert and look for new-onset proteinuria, sudden increase of a BP that was previously well controlled, thrombocytopenia, increased liver enzymes or fetal growth restriction. Once preeclampsia is diagnosed, antepartum testing is essential until 37 weeks; then delivery is indicated. Delivery is always best for maternal health.

Intrapartum treatment goals are to prevent seizures and control hypertension. Magnesium sulfate is given to control seizures, not to control blood pressure, and is used for both preeclampsia and eclampsia. Anti-hypertensive therapy is aggressive and swift.

While controlling the blood pressure is important, it does not halt the disease progression; the disease continues to evolve even with blood pressure correction. Risk reduction and safe outcomes require prompt hypertensive management with the use of standardized treatment. Severe hypertension needs to be treated within 30-60 minutes of diagnosis of severe hypertension. (Severe hypertension is a BP >160/110 that persists for 15 minutes.) ACOG and CMQCC have emphasized the importance of expediency of diagnosis and treatment regarding blood pressure elevation in order to prevent maternal stroke or hemorrhage. Fast and swift action is imperative to reduce the incidence of poor maternal outcomes.

In April 2017, ACOG released standardized treatment guidelines for treatment of severe hypertension. Institutions should have protocols in place that address the importance of fast, standardized emergency intervention to decrease blood pressure in a hypertensive crisis. Treatment with a first-line drug agent should occur within 30-60 minutes of confirmed severe hypertension to reduce the chance of stroke. Labetalol, hydralazine, and oral nifedipine will become your closest allies in fighting fight severe blood pressures. Pregnant patients or patients in the postpartum period with severe hypertension need to be treated with first-line agents of IV labetalol or IV hydralazine; immediate-release oral nifedipine may also be considered as a first-line agent if IV access is not available. (Oral labetalol can be a consideration if IV access has not been established and oral nifedipine is not accessible.) 

See the ACOG Committee Opinion “Emergent Therapy for Acute-Onset Severe Hypertension During Pregnancy and Postpartum Period” (Number 692, April 2017) for first-line medication dosing, standardized order sets, guidelines for escalation of treatment, and frequency of VS checks. There are also easily readable algorithms that review each medication listed in the ACOG Maternal Safety Bundle for Hypertension 2015. These easy-to-follow algorithms help give clarity to administering the medications, waiting for response, and frequency of evaluation of BP. It is highly recommended to laminate these algorithms and post them on your unit.

Hospitals need to ensure that RNs from L&D, ED, AP and PP are all able to access these order sets and give the appropriate first-line medications without having to wait to transfer a patient to another unit prior to administration. It is important for the RN to immediately notify the physician of the elevated BP, take swift action to provide first-line medications within 30-60 minutes, and initiate fetal surveillance as soon as possible.

Each first-line medication does pose potential risks. IV hydralazine increases the chance of maternal hypotension with a systolic BP of 90 or less. IV labetalol may cause neonatal bradycardia and should be avoided in women with asthma, heart disease or congestive heart failure. Nifedipine can cause maternal tachycardia and overshoot hypotension. Nifedipine should not be give SL, as it can cause hypotension. None of these three medications have shown any change in umbilical blood flow to the fetus.

The goal of treatment is not to normalize BP, but rather to get it into an acceptable range of 140-150/90-100 or lower in order to prevent prolonged exposure to elevated levels that cause loss of cerebral vasculature autoregulation. In the event of a prolonged, uncontrolled hypertensive crisis, it is necessary to achieve maternal stabilization prior to delivery. If there is going to be a transfer to a tertiary care setting, BP stabilization and initiation of magnesium sulfate should occur prior to transfer. Magnesium sulfate is not used to control BP, but it is used for seizure prophylaxis in both preeclampsia and eclampsia. Since intubation is known to increase BP, it should not be started until steps have been taken to try to eliminate or minimize a hypertensive response to intubation. ACOG recommends judicious fluid administration even in the case of oliguria.

In the rare instance that one of these three agents fails to decrease the BP when given in successive appropriate doses, then emergency consultation of an MFM specialist, anesthesiologist or critical care subspecialist should be considered to address emergency second-line recommendations. Considerations for treatment of resistant hypertension include nicardipine or esmolol by infusion pump. Nipride is reserved for extreme emergencies in the severest of cases because of the concerns of fetal toxicity or the chance of increasing cerebral edema in the patient.

HELLP Syndrome

HELLP syndrome, which is an acronym for hemolysis, elevated liver enzymes, low platelets, greatly increases the incidence of maternal morbidity and mortality; it occurs in 20% of women diagnosed with preeclampsia and is considered the severest form of preeclampsia.

HELLP syndrome is further divided into three classes by abnormal lab findings, which reflect the condition of the mother’s blood vessels and liver.

• Class I:     Platelets <50K, AST ≥70 IU/L, LDH ≥600 IU/L
• Class II:    Platelets >50K and <100K, AT >70, LDH >600 IU/L
• Class III: Mild thrombocytopenia platelets nadir between 100K and 150K, AST >40 IU/L, LDH >600 IU/L

Ten percent to 80% of patients are diagnosed between 28 and 36 weeks, and 30% are diagnosed within 48 hours post-delivery. Twenty percent of HELLP patients will develop DIC, and 20% will be absent of hypertension. It is important to note that up to 15% of HELLP patients will not have an elevated blood pressure and up to 25% have absence of proteinuria. Hence, elevated BP and proteinuria are not necessary for diagnosis of HELLP. Classic features of unremitting headache, epigastric pain, nausea, vomiting or vision changes should prompt further evaluation to rule out disease progression and the need for immediate delivery. The most common reasons for the mother to become critically ill with HELLP syndrome are liver rupture or stroke, which is due to either cerebral edema or cerebral hemorrhage. Outcomes are improved by early diagnosis and delivery.

In addition to DIC, HELLP syndrome predisposes the patient to a multitude of comorbidities, including: preterm birth, hepatic hematoma, placental abruption, renal failure, and maternal and fetal death; fetal death can occur in up to 35% of cases. (Delay of delivery in the patient with HELLP syndrome is usually not recommended; however, if maternal-fetal status is stable, waiting 24-48 hours to provide ACS is reasonable.)

Eclampsia

Mortality rates for both mother and baby increase when eclampsia occurs. As the disease progresses, uric acid and creatinine toxins start to build up because they are not being cleared by the kidneys. These poisonous toxins can lead to a seizure, sometimes even a secondary seizure. During a seizure, there is the potential for an obstructed airway, loss of respirations and development of metabolic acidemia. Airway management should be your number one priority and should take precedence over mag sulfate administration. Many of the sequelae of seizures such as brain hemorrhage and maternal hypoxia leading to fetal hypoxia are due to cessation of respirations. The fetus will experience bradycardia for 3-8 minutes post-maternal seizure. Maternal stabilization and intrauterine resuscitation will most likely be needed.

Reminder: Magnesium sulfate is the medication of choice. However, magnesium is cleared by the kidneys, and if the patient has renal compromise and poor renal perfusion, magnesium levels will need to be monitored closely to ensure that toxic levels do not occur. Calcium gluconate is the antidote, and it should be readily available. Magnesium is a high-alert medication requiring 2 RNs for identification and an RN present at bedside during administration of the loading dose. The loading dose is 4gm; maintenance is 2-3 gm/hr or 6 gm loading and then 3gm/hr per infusion pump. Since magnesium is a calcium channel blocker, it should not be given with other calcium channel blockers.

Future Risk

Patients with preeclampsia are at an increased lifetime risk for cardiovascular disease. Women who have had preeclampsia are at double the risk for heart disease and stroke over the next 5 to 15 years. Reoccurrence rates for preeclampsia range from 5% to 70%. Women who experience a repeat diagnosis of preeclampsia in another pregnancy are at even greater lifetime risk for cardiovascular issues.

Many of the problems surrounding preeclampsia and its outcomes come down to the very basics of our health provider education. The following are some basics that apply to many scenarios, but they are truly crucial regarding preeclampsia and eclampsia and their consequences.

• Know the current preeclampsia practice updates and terminology.
• Recognize risk factors for preeclampsia.
• Know and identify the signs/symptoms of preeclampsia.
• Aim for early recognition and intervention.
• Closely monitor BP and understand BP history (know your baseline early pregnancy and pre-pregnancy values).
• Know when to call for help and seek expert counsel.
• Severe hypertension requires rapid intervention within 30-60 minutes of dx with first-line meds.
• Have the support of an experienced team that has practiced drills and simulations on how to manage eclampsia.
• Use standardized evidenced-based treatment and guidelines as seen in the CMQCC preeclamptic toolkit and ACOG’s Safe Motherhood Initiative safety bundles for hypertension

(algorithms for suspected preeclampsia, treatment and eclampsia care, tool for early recognition of preeclampsia, etc.).

• Provide postpartum discharge education with warning signs/symptoms so patients are aware of them.
• Ensure adequate post-delivery follow-up and include interdisciplinary team (cardiologist, etc.).
• Make sure the patient is aware of the long-term sequelae and that future follow-up will be necessary.
• Encourage patients to have healthy lifestyle choices, an awareness of risk factors, an awareness of their health histories and family health histories, and to know their blood pressures and lab values.

Patient Education

Patients need to know that this disease can strike quickly and have devastating consequences for both mother and baby. They need to be educated to recognize the signs and symptoms and know when to seek help in order to help reduce poor outcomes. Women should know that any of the following signs/symptoms require immediate medical attention:

• Swelling of hands or feet
• Weight gain of >5 pounds in one week
• Unrelenting headache not resolved with OTC medications
• Vision changes
• Sudden nausea or vomiting
• Right upper quadrant abdominal or chest pain
• Cough
• Difficulty breathing or shortness of breath

It is also important to know that some women do not experience any of the traditional warning signs and symptoms; hence, the importance of compliancy with attending all prenatal visits. Early risk identification and early intervention with continued maternal-fetal surveillance will help to mitigate disease severity. Engaging institutions to utilize best practices and standardized tools such as those provided by ACOG Safe Motherhood Initiative safety bundle for severe hypertension and the toolkit in the CMQCC pack provide the opportunity to optimize outcomes.

At the time of postpartum discharge, women need to be notified of the importance of a blood pressure check in the next 3-4 days, and they need to be educated about the warning signs and symptoms of eclampsia. Eclamptic seizures can occur up to 6 weeks post-delivery. Seventy-eight percent of postpartum eclampsia occurs in women with no history of hypertensive disease in pregnancy. But it is helpful to know that 69% of these patients present with headache; any woman presenting to the ED for headache who has had a recent pregnancy should be evaluated for delayed preeclampsia.

Discharge instructions to the postpartum preeclamptic or eclamptic patient are crucial; the CMQCC toolkit provides standardized examples.

Women need to be aware that they are at increased risk for all forms of preeclampsia in subsequent pregnancies. The rate of recurrent HELLP syndrome ranges from 2%-19%. The rate of preeclampsia in subsequent pregnancies is 16%-52%. Patients who do experience another pregnancy and have preeclampsia are at even higher risk for long-term cardiovascular issues.

It should also be recognized that short intervals between pregnancies is recommended because intervals protect from future preeclampsia severity. The thought is that a short pregnancy interval is safer because the vasculature of the uterus has already been remodeled, but waiting long intervals between pregnancies causes the vessels to return to a state similar to the original pregnancy. If there is short interval spacing to a subsequent pregnancy, sFlt can be reduced by as much as 30%, which decreases the chance of ischemia.

The Preeclampsia Foundation raises public awareness to the disease and helps to catalyze research that will improve healthcare practices and outcomes. Their website provides information about the latest research updates on the disease and provides links to many valuable resources. Patients who have experienced preeclampsia first-hand should share their knowledge and experiences with the preeclampsia registry.

HCP Resources

The California Preeclampsia Toolkit, released in January, 2014, was developed by the California Maternal Quality Care Collaborative (CMQCC) Preeclampsia Task Force, co-chaired by ACOG District IX Fellows Maurice Druzin, MD and Laurence Shields, MD and CMQCC Clinical Director Nancy Peterson, RNC, PNNP.

First Trimester Risk Assessment for Early-Onset Preeclampsia. ACOG Committee Opinion for Obstetrics Number 638, issued by ACOG and endorsed by the Society for Maternal-Fetal Medicine in September 2015, are guidelines developed by the Committee on Obstetric Practice for providers.

Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. ACOG Committee Opinion Number 692, issued by ACOG in April 2017, are guidelines developed by the Committee on Obstetrics Practice for providers.

California Preeclampsia Toolkit

Maternal Safety Bundle for Severe Hypertension in Pregnancy, issued on January 14, 2014, is a slide set for ob-gyns and healthcare providers developed as part of the Safe Motherhood Initiative, a collaborative project of ACOG, District II, and the New York State Department of Health’s Bureau of Women’s Health.

Task Force Report on Hypertension in Pregnancy

ACOG’s Continuing Commitment to Preeclampsia Progress by James N. Martin, Jr, MD. In this article, published on May 23, 2014, Dr. Martin, who served as ACOG President from 2011 to 2012, provides insight into the origins of preeclampsia task force report—and a road map for future progress.

Patient Resources

Preeclampsia and High Blood Pressure During Pregnancy. Issued by ACOG in August, 2011.

Organizations

The Preeclampsia Foundation is a non-profit organization that provides patient education and support for people whose lives have been or will be affected by preeclampsia: mothers, babies, fathers, and their families. ACOG is a Preeclampsia Month Awareness Partner with the foundation.

The University of Oxford's iHOPE project aims to improve preeclampsia research by developing a core set of maternal and offspring outcomes that would be common to all future preeclampsia research and that would to enable healthcare professionals to provide better treatments and care for pregnant women and their babies.

The Council on Patient Safety in Women’s Health Care’s Severe Hypertension Patient Safety Bundle focuses on the implementation of the ‘4 R’ domains: Readiness, Recognition, Response, and Reporting. The Alliance for Innovation on Maternal Health (AIM) Program created a series of AIM eModules based on the Severe Hypertension Patient Safety Bundle.

Patient Safety Bundle: Severe Hypertension