Author: Harry Nonez, MD
Edited by: Nicole Anthony, MD

You are a senior resident working in the critical care area of a busy ED. You are juggling eight patients, and the triage nurse pulls you aside to evaluate another one. The patient is a 35-year-old woman at 37 weeks gestation who is presenting with a severe headache and acute abdominal pain. She had a routine prenatal visit four days ago at which she was asymptomatic, and her prenatal care has been uncomplicated thus far. On your initial evaluation, the blood pressure is 165/110 mm Hg; the patient is alert and oriented, her abdomen is gravid and tender in the right upper quadrant, there is no fundal tenderness, and there is 2+ pitting edema to the knees bilaterally.

Although we don’t see many pregnant patients over 20 weeks gestation in our ED, it is important to know how to manage this very common obstetrical emergency. Hypertensive disorders are among the most common medical complications of pregnancy, affecting about 7-10% of all pregnant women. 

Understanding Types of Hypertensive Disorders in Pregnancy

When it comes to hypertension in pregnancy, it’s important to know the different sub-categories ranging from mild to dangerous. The mildest condition is chronic hypertension. Chronic hypertension is usually present before pregnancy or diagnosed within the first 20 weeks of gestation. Pregnancy-related hypertension usually resolves following delivery, although the exact timeline for resolution is unknown. One should suspect occult chronic hypertension if elevated pressures persist more than 12 weeks postpartum.[1]

Hypertensive disorders of pregnancy make up a spectrum of disorders that stem from the pregnancy itself and, by definition, are limited to new hypertension diagnosed after 20 weeks gestation. The American College of Obstetrics and Gynecology defines mild-range hypertension in pregnancy as a systolic blood pressure ≥140 mm Hg and/or a diastolic pressure ≥90 mm Hg on two occasions at least 4 hours apart in a woman who previously had normal blood pressure; when this occurs at >20 weeks gestation, the patient is diagnosed with gestational hypertension.[1] On the other end of the spectrum are the more dangerous entities, preeclampsia and eclampsia. 

Preeclampsia is diagnosed when a patient meets gestational hypertension criteria AND has proteinuria (≥300 mg in 24 hrs or a random urine protein/creatinine ratio ≥ 0.3).[2] Preeclampsia is an inflammatory vascular disorder caused by the placental-fetal unit and systemically impacts all end organ systems. Even in the absence of proteinuria, a woman can be diagnosed with preeclampsia if severe features are present (reflecting injury and dysfunction of an end organ) or severe-range blood pressures (≥160 mm Hg systolic or ≥110 mm Hg diastolic on two occasions at least four hours apart OR sustained for 15 minutes requiring IV antihypertensive therapy).

This disease increases the risk for complications such as liver capsule hematoma/rupture, stroke, coagulopathy, hemolysis, placental abruption, and seizure.

Eclampsia is a neurologic manifestation of severe preeclampsia, defined by tonic-clonic focal/multifocal seizures without another cause and often preceded by a headache, altered mental status, or visual disturbance.[1,3] Eclampsia may occur at any point during the puerperium but is most likely to occur during the intrapartum period or within 48 hours after delivery.[4,5] Patients with eclampsia may have an increased risk for the development of cardiovascular and cerebrovascular disease and diabetes later in life.[6,7] Progression of preeclampsia to eclampsia is unpredictable, can occur suddenly, and is not contingent upon severe dysfunction in the other organ systems. All preeclamptic patients should be closely monitored.[5] 

HELLP syndrome is another life-threatening obstetric complication considered to be a variant of preeclampsia that impacts the hepatic and hematologic organ systems.[8] HELLP is an acronym that reflects the diagnostic features of the disease:

★ Hemolysis (usually LDH ≥ 600 IU/L)
★ Elevated Liver enzymes (LFT > 2x upper limit of normal)
★ Low Platelets (Plt < 100 x 109/L)

HELLP syndrome is characterized by hepatic and coagulation cascade involvement, increased vascular tone, and platelet aggregation.[9] It is important to note that this disorder can have an insidious onset and up to 15% of cases occur in the absence of hypertension or proteinuria. Severe cases can result in consumptive coagulopathy and liver hemorrhage/necrosis, placing the patient at risk for developing liver capsule hematomas and rupture. 

Evaluation

First and foremost, make sure you are cycling the patient’s blood pressure every hour (at a minimum), and as frequently as every 15 minutes if the pressure is severe-range. Assess maternal mental status and look for symptoms and signs of end-organ damage, such as severe headache, visual disturbance, hypoxemia, pulmonary crackles, and right upper quadrant or epigastric pain. After assessing the patient, assess the fetus by confirming fetal movement and obtaining the heart rate. A fetal heart rate that is too low (<110/min) or too high (>160/min) may indicate fetal distress and need for urgent maternal resuscitation or delivery. Although these patients should, ideally, be transferred from the ED to the Labor and Delivery unit for further management by our Obstetric colleagues, it is imperative to know how to diagnose and stabilize a preeclamptic patient if necessary. 

While most preeclampsia occurs during the third trimester, women are still at risk in the second trimester and the immediate postpartum period. If a recently postpartum patient comes in with tell-tale signs of preeclampsia, don’t rule out the disease simply because she has delivered – i.e. if it looks like a duck and quacks like a duck, it’s probably a duck!

Testing

The laboratory workup for a patient with suspected preeclampsia focuses on identifying end-organ dysfunction. 

1. BMP (renal – creatinine)
2. Hepatic panel
3. CBC (heme – platelets)
4. Random urine protein/creatinine ratio (renal)
5. LDH (heme)
6. Uric acid (renal)
7. Type & Screen
8. Consider PT, aPTT, fibrinogen (heme)

You are unlikely to obtain a full 24-hour urine protein collection in the ED, so a random urine protein is the more practical and common testing method.

Serum uric acid is not part of the diagnostic criteria for preeclampsia but is another marker of renal dysfunction and can be seen in patients developing preeclampsia.[10,11]

Since these patients may require delivery, a T&S should always be sent.

A peripheral smear of the blood may also identify signs of microangiopathic hemolysis such as schistocytes and burr cells. Prothrombin time, partial thromboplastin time, and fibrinogen levels are usually normal, but if coagulation times are prolonged and fibrinogen levels are decreased, disseminated intravascular coagulation should be suspected.

Treatment  

Since all hypertensive disorders of pregnancy stem from the pregnancy itself, the ultimate treatment is DELIVERY. In the ED, your objective is to comprehensively assess the patient, make the diagnosis, and stabilize the patient to minimize the risk of sequelae (think – stroke and seizure prevention)! Of course, don’t forget to call OB emergently for severe-range blood pressure or signs of eclampsia. 

In the meantime, systolic and diastolic blood pressure should be maintained below the severe-range (SBP < 160 and DBP < 110 mm Hg).[4,5] If a patient is having sustained (persistent readings 15 minutes apart), severe-range hypertension, immediately treat with an immediate-acting agent, such as intravenous labetalol or hydralazine to help prevent stroke.[12] Start with monotherapy until you reach the maximum dose before adding a second agent. Oral immediate-release Nifedipine is an alternative if immediate IV access cannot be established.[12] Since timely treatment is crucial to reducing maternal morbidity, simple algorithms have been established for the management of acute hypertensive emergencies in pregnancy by ACOG’s Safe Motherhood Initiative (there’s an app for that)! These algorithms guide you through the dosing of each antihypertensive agent, the timing of redosing, and the timing for transitioning to an alternative agent in refractory cases.

 

Labetalol Algorithm

 

Hydralazine Algorithm

 

Nifedipine Algorithm

While controlling the blood pressure in your severely preeclamptic patient, you should also be preparing magnesium sulfate for eclampsia prophylaxis. Magnesium sulfate is given as a loading dose of 4  to 6 g IV followed by 2 g per hour for at least 24 hours postpartum. Oliguria from renal dysfunction (which can be seen in pre-eclampsia and eclampsia) may lead to toxic magnesium levels, so it is important to track the patient’s urine output during magnesium therapy.

Clinical assessment should be done serially to assess for magnesium toxicity, and the infusion should be discontinued if there is suspicion of toxicity. The serum magnesium level may not always correlate with toxicity (but many institutions still require getting a magnesium level), so correlate with the following symptoms: 

★ loss of reflexes (occurs at a serum level > 9 mg/dL) [1,13] respiratory depression (occurs at a serum level > 12 mg/dL) [1,13] ★ cardiac arrest (occurs at a serum level > 30 mg/dL)[1]

If you cannot administer magnesium intravenously, administer 5 grams intramuscularly in each buttock for a total of 10 grams, followed by 5 grams every 4 hours to achieve maintenance. There is a higher rate of magnesium toxicity associated with intramuscular administration.

Calcium gluconate (1 g) is the antidote for magnesium toxicity.

Disposition

Whether a patient with a hypertensive disorder of pregnancy can go home or needs admission to Obstetrics depends on the degree of blood pressure elevation.[8]

Mild elevations in blood pressure and no evidence of proteinuria or end-organ dysfunction (i.e. chronic or gestational hypertension): discharge home with close follow-up and home blood pressure monitoring.

Chronic hypertension in pregnancy: can have blood pressures in mild-range (SBP > 140 mm Hg or DBP > 90 mm Hg) as long as they are below severe-range (SBP ≥ 160 mmHg and/or DBP ≥110 mm Hg on 2 occasions ≥4 hours apart OR sustained 15 minutes apart).
➡ If during the ED stay, the patient is consistently in high- or mild-range (SBP > 150 mm Hg or DBP > 100 mm Hg), you can initiate labetalol 200 mg twice daily or nifedipine XL 30 mg daily.
Gestational hypertension is not treated with maintenance oral antihypertensive medications as you do NOT want to mask progression to preeclampsia.

Preeclampsia: admission for close observation, further management, and possible delivery.

Case Summary

A 35-year-old woman at 37 weeks gestation (with uncomplicated prenatal care) presented with severe headache and acute abdominal pain. Her initial blood pressure was 165/110 mm Hg and 172/110 mm Hg 15 minutes later. Her labs were notable for mild transaminitis and an elevated urine protein/creatinine ratio of 0.35. Obstetrics was consulted, and the patient was stabilized with 20 milligrams of intravenous labetalol followed by additional 40 milligrams with resolution of severe-range hypertension. She was transferred to the Labor and Delivery unit by the ED team and delivered a few hours later. Mom and baby recovered well. 

KEY POINTS

1. Preeclampsia currently remains one of the leading causes of death and severe maternal morbidity.
2. Mild-range hypertension in pregnancy is a systolic blood pressure of ≥ 140 mm Hg and/or a diastolic pressure of ≥ 90 mm Hg on two occasions at least 4 hours apart in a woman who previously had normal blood pressure.
3. Severe-range hypertension in pregnancy is a systolic blood pressure of ≥ 160 mm Hg and/or a diastolic blood pressure ≥110 mm Hg on two occasions ≥4 hours apart OR sustained 15 minutes apart.
4. Look for end-organ dysfunction by checking the following labs: hepatic panel, CBC, random urine protein/creatinine, LDH, Uric acid, T&S, PT/INR, aPTT.
5. Download ACOG’s Safe Motherhood Initiative app for algorithms as a guide for the dosing of each antihypertensive agent, or visit it online.
6. New-onset seizures that occur between 48 hours and 4 weeks after delivery should be considered late-onset eclampsia until proven otherwise.
7. Although a patient with preeclampsia may look well, they should all be considered for admission and close monitoring.

Resources

1. Hypertension in pregnancy: Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122:1122.
2.
Brown MA. Lindheimer MD. de Swiet M. Van Assche A. Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). [Review] [8 refs] [Consensus Development Conference. Editorial. Review] Hypertension in Pregnancy. 20(1):IX-XIV, 2001.
3. Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ. 1994;309:1395-1400.
4. Mattar F, Sibai BM. Eclampsia. VIII. Risk Factors for maternal morbidity. Am J Obstet Gynecol. 2000;182:307-12
5. Katz VL, Farmer R, Kuller J. Preeclampsia into eclampsia: a New paradigm. Am J Obstet Gynecol. 2000;182:1389-96.
6. Sibai BM, Mercer B, Sarinoglu C. Severe preeclampsia in the second trimester: recurrence risk and long-term prognosis. Am J Obstet Gynecol 1991; 165:1408.
7. Behrens I, Basit S, Lykke JA, et al. Association Between Hypertensive Disorders of Pregnancy and Later Risk of Cardiomyopathy. JAMA 2016; 315:1026.
8. Keadey M, Houry D. Complications In Pregnancy Part II: Hypertensive Disorders Of Pregnancy And Vaginal Bleeding May 2009; Volume 11, Number 5.
9. Khalid F, Tonismae T. HELLP Syndrome. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
10. Bainbridge SA, Roberts JM. Uric acid as a pathogenic factor in preeclampsia. Placenta. 2008 Mar;29 Suppl A(Suppl A):S67-72. doi: 10.1016/j.placenta.2007.11.001. Epub 2008 Feb 21. PMID: 18093648; PMCID: PMC3319018.
11. Johnson RJ, Kanbay M, Kang DH, Sánchez-Lozada LG, Feig D. Uric acid: a clinically useful marker to distinguish preeclampsia from gestational hypertension. Hypertension. 2011 Oct;58(4):548-9. doi: 10.1161/HYPERTENSIONAHA.111.178921. Epub 2011 Aug 29. PMID: 21876074; PMCID: PMC3203211.
12. Podymow T, August P. Update on the use of antihypertensive drugs in pregnancy. Hypertension. 2008;51(4):960-969.
13. Grissinger M. Preventing Magnesium Toxicity in Obstetrics. P T. 2009 Aug;34(8):403. PMCID: PMC2799127.

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