Severe Preeclampsia Case File

Severe Preeclampsia Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 17

An 18-year-old G1P0 Hispanic female at 28 weeks’ gestation comes into the obstetrical triage unit complaining of decreased fetal movement and headache. Her prenatal history is unremarkable. Her blood pressures in the first trimester was in the 100/60 mm/Hg range. On examination, her BP is 170/110 mm Hg, HR 98 beats per minute, temperature 98.4°F, and RR 12 breaths/min. Her heart and lung examinations are normal. The abdomen is nontender and the fundal height is 27 cm. The fetal heart tones are in the 135 beats per minute range with occasional variable decelerations on external fetal monitoring. There are no uterine contractions. The vaginal examination reveals that the cervix is closed, long, and posterior. The CBC shows a hemoglobin level of 12 g/dL, plt = 110,000, glucose = 98 mg/dL, SGOT = 32 IU/L and SGPT = 28 IU/L, and LDH = 102 mg/dL. Serum creatinine level is 0.6 mg/dL. The urinalysis shows 3+ protein on dipstick.

➤ What is the most likely diagnosis?

➤ What are your next steps?

➤ What are the important considerations in managing her pregnancy?

ANSWERS TO CASE 17:

Severe Preeclampsia

Summary: An 18-year-old G1P0 Hispanic female at 28 weeks’ gestation has decreased fetal movement and headache. Her BP is 170/110 mm Hg, and fundal height is 27 cm. The fetal heart tones are in the 135 beats per minute range with occasional variable decelerations without contractions. The cervix is unfavorable. The CBC shows a hemoglobin level of 12 g/dL, plt 110,000/mm3, glucose 98 mg/dL, SGOT 32 IU/L, SGPT 28 IU/L, LDH 102 mg/dL, and creatinine 0.6 mg/dL. The urinalysis shows 3+ protein on dipstick.

➤ Most likely diagnosis: Severe preeclampsia.

➤ Next steps: (1) Initiate bed rest and serial blood pressure measurements, (2) fetal ultrasound and biophysical profile, and (3) characterization of the headache to assess for severe neurologic threat.

➤ Important management considerations: If the patient is felt to have severe preeclampsia of sufficient threat to either maternal or fetal well-being, then magnesium sulfate should be initiated, and plans made to proceed with delivery. However, often with bed rest, the blood pressure and headache will subside. If the patient can be stabilized and fetal well-being is assured, expectant management may be considered. If expectant management is chosen, then it would be appropriate to begin magnesium sulfate, administer corticosteroids, start a 24-hour urine protein collection, and begin serial laboratory studies to evaluate the patient for HELLP syndrome.

ANALYSIS

Objectives

1. Be able to describe the diagnostic criteria of preeclampsia and severe preeclampsia.
2. Be able to describe the diagnostic and management approach to preeclampsia.
3. Be able to discuss the considerations of managing severe preeclampsia in a preterm gestation.
4. Be able to describe the complications of severe preeclampsia.

Considerations

The first responsibility of the obstetrician to any patient with preeclampsia is to stabilize the mother and assess the well-being of her fetus. This patient’s severe hypertension will need to be treated aggressively if it is not responsive to bed rest alone. The goal of antihypertensive therapy is to keep the systolic blood pressure less than 160 mm Hg and the diastolic pressure less than 100 mm Hg. Apresoline (hydralazine), labetalol, or nifedipine are antihypertensive medications that are commonly used for control of blood pressure. Her platelet count of 110,000/mm3 is concerning for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and these labs will need to be followed closely for significant changes. Her headache is concerning for the possibility of an impending seizure. If it does not resolve with bed rest or if she has other signs of CNS irritability, such as visual disturbances, clonus, or change in mental status, then magnesium sulfate for seizure prophylaxis should be started immediately. Urinary output should be measured on an hourly basis and collected for measurement of urinary protein. Fetal assessment is also critical. Continuous electronic fetal monitoring, a biophysical profile, or Doppler assessment of the fetal vessels are common ways to assess the fetus for evidence of uteroplacental insufficiency and significant compromise. Evaluation of the fetus for intrauterine growth restriction should be done as well. Delivery is the only “cure” for her preeclampsia.

In cases of fetal immaturity (< 34 wk gestation), expectant management may be considered if the fetal status is reassuring, the maternal condition can be stabilized, and the patient is in a carefully monitored care unit with experienced nurses and physicians. The primary consideration in this case would be gaining time to administer antenatal corticosteroids for the benefit of the premature fetus. There are no maternal benefits to expectant management. Assuming that the diagnosis of severe preeclampsia is confirmed, magnesium sulfate should be started, and the patient’s blood pressure should be kept less than 160/100 mm/Hg. Betamethasone or dexamethasone should be started as soon as possible. Diminished urine output is common and while excessive proteinuria (> 5 g/24 h) is indicative of severe disease, it alone is not an indication for delivery. Further decrease in her platelet count, increase in her liver enzymes, or elevation of her LDH are all signs of worsening HELLP syndrome. At this point, expectant management should be reassessed and delivery considered. Poorly controlled hypertension, seizures, evidence of pulmonary edema, placental abruption, or signs of fetal compromise would be indications for delivery irrespective of gestational age. Once a course of corticosteroids for the fetus has been completed, the situation should be reevaluated. Further delay may be considered if the maternal and fetal status are stable and the benefits of delay outweigh the risks of continuing the pregnancy. Vaginal delivery is not contraindicated, but rapid deterioration of the fetal status and/or maternal condition may dictate an expedited delivery by cesarean section. The anesthesiologist should be made aware of the mother’s status and neonatology should be present for the delivery of this premature infant.

APPROACH TO

Severe Preeclampsia

Preeclampsia is a complication of human pregnancies occurring in 5% to 8% of all pregnant patients, and is a leading cause of maternal and fetal morbidity and mortality. Preeclampsia is, by definition, the development of new-onset hypertension (BP ≥140/90 mm Hg) and proteinuria (greater than 300 mg/24 h) in the mother after the 20th week of gestation. Currently, preeclampsia is designated as “mild” or “severe” based on several clinical and laboratory parameters. Mild preeclampsia is defined as a systolic blood pressure ≥ 140 mm Hg and a diastolic blood pressure ≥ 90 mm Hg in a previously normotensive pregnant patient, and the presence of ≥ 300 mg of protein in a 24-hour urine collection in a patient without previous renal disease.1 In addition to these clinical parameters, the patient should have no other complaints or laboratory abnormalities and her fetus should exhibit normal growth. Severe preeclampsia is defined as a systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 110 mm Hg, ≥ 5 g of urinary protein excretion per 24 hours, plus evidence of other organ system involvement such as impaired liver function, thrombocytopenia, oliguria (≤ 500 mL in 24 h), pulmonary edema, epigastric or right upper quadrant pain, cerebral or visual disturbances, and/or fetal growth restriction.1 In some cases, patients with chronic hypertension may have superimposed preeclampsia. Gestational hypertension is new-onset hypertension after the 20th week of gestation without the development of proteinuria. Lastly, the development of grand mal seizures in a patient with preeclampsia is defined as eclampsia. Our discussion will focus on severe preeclampsia.

Risk Factors and Etiology

Preeclampsia is unique to human pregnancies and generally thought of as a disease of nulligravid women. Seventy-five percent of cases are seen in pregnancies near term or intrapartum.2 These cases are generally mild and not usually associated with significant complications or adverse outcomes. Cases of severe preeclampsia are often seen in patients with underlying maternal diseases and usually occur earlier in the third trimester of pregnancy. Commonly accepted risk factors for the development of preeclampsia include maternal obesity, advanced maternal age, chronic hypertension, diabetes, multifetal gestation, and African American ethnicity.8 A maternal history of connective tissue disease, thrombophilia, or a family history of preeclampsia also increases a person’s risk of preeclampsia. Pregnancy-related risk factors include molar pregnancies, fetal triploidy, a previous pregnancy complicated by preeclampsia or gestational hypertension, and unexplained fetal growth restriction.8 There are no tests which are reliable in predicting the onset or severity of the disease.5

The etiology of preeclampsia is unknown. In the early 20th century, it was thought to be caused by fetal “toxins” which crossed the placenta and entered the maternal circulation.3 Today, it is thought of as a multifactorial process involving abnormal trophoblast invasion of the uterine vessels, immunologic intolerance, maternal maladaptation to cardiovascular or inflammatory changes of pregnancy, and genetic influences.4 These abnormalities lead to reduced uteroplacental blood flow, endothelial cell dysfunction, an imbalance of pro- and antiangiogenic factors, and alterations in prostaglandin production.8 The result is intense vasospasm, systemic hypertension, capillary leakage, and other changes which result in multiorgan dysfunction. While the etiology is still uncertain, several studies have looked at various treatment modalities to prevent preeclampsia. Unfortunately no reliable treatment or supplementation regimen has shown consistently favorable results.5

Diagnosis and Differential Diagnosis

The diagnosis of preeclampsia requires regular assessment of the pregnant patient and a high degree of suspicion. Properly performed blood pressure measurements are essential for the proper diagnosis. Measurements must be performed with the appropriate size blood pressure cuff to be accurate. The patient should be sitting and allowed to rest for a few minutes before checking her blood pressure. Judgment should not be made with just one abnormal reading, and serial measurements will often clarify the clinical picture. The patient may have several complaints or be completely asymptomatic. The hypertensive patient should be questioned for the presence of a severe, longlasting, frontal or occipital headache, blurry vision, or scotomata. It is also important to know if she has abdominal or epigastric pain, nausea, vomiting, or decreased fetal movement. On physical examination, significant weight gain over a short period of time may be an important clinical sign, as is pronounced edema in nondependent areas. On abdominal examination one should look for right upper quadrant abdominal pain or uterine tenderness and an appropriate fundal height. While fetal growth abnormalities are not diagnostic of preeclampsia, the presence for intrauterine growth restriction in patients with preeclampsia is indicative of severe disease. Signs of hyperreflexia are worrisome for an impending seizure. Proteinuria may be variable and, if more than 1+ on a urine dipstick, a 24-hour urine collection for total urinary protein and creatinine clearance should be started. Once the patient is thoroughly evaluated and laboratory assessments are complete, a determination can then be made as to whether or not the patient has preeclampsia and if so, if it is mild or severe disease.

The differential diagnosis of preeclampsia may include pyelonephritis, cholelithiasis, appendicitis, gastroenteritis, and/or renal stones. Most of these conditions can be distinguished by a complete medical history, thorough physical examination, and appropriate laboratory studies. Although rare, other conditions may mimic severe preeclampsia. These conditions include acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, systemic lupus erythematosus with lupus nephritis, systemic viral sepsis, and systemic inflammatory response syndrome.6 These microangiopathic disorders have many of the same clinical and laboratory findings as severe preeclampsia with HELLP syndrome. Each disorder has some distinguishing features which can be identified if the diagnosis is suspected. Treatment strategies are based on the specific disease process and delivery may or may not be indicated.

Management

If the patient is found to have blood pressures ≥ 160 mm Hg systolic or ≥ 110 mm Hg diastolic, proteinuria ≥ 5 g in a 24-hour urine collection, oliguria (≤ 500 cc/24 h), cerebral or visual disturbances, epigastric or right upper quadrant abdominal pain, pulmonary edema, thrombocytopenia (< 100,000/mm3), or fetal growth restriction, she/he meets the criteria for severe preeclampsia.1 Management of severe preeclampsia calls for careful monitoring of both the maternal and fetal condition, and may be influenced by the gestational age of the fetus at the time of diagnosis. Delivery is the only cure, and the health of the mother should be the primary concern. Blood pressures should be kept below 160/100 mm Hg to avoid cerebral vascular accidents in the mother. Labetalol has replaced hydralazine as the drug of choice for treating severe hypertension in many centers. It may be given as 20 to 40 mg IV every 10 to 15 minutes for a maximum of 220 mg. Invasive cardiovascular hemodynamic monitoring is rarely necessary. Urinary output must be closely monitored for the development of severe oliguria. Urinary excretion of protein should be measured on a regular basis. Seizure prophylaxis with magnesium sulfate is recommended, especially if there are signs of CNS irritation.

Most protocols for magnesium sulfate recommend an IV bolus of 4 to 6 g over 20 minutes, followed by an infusion of 1 to 2 g per hour. This is usually continued throughout labor and for the first 24 hours of the postpartum period. The patient should be monitored closely for respiratory depression, a primary concern with magnesium sulfate therapy. Laboratory studies to screen for HELLP syndrome are important as changes in these parameters may be unrecognized clinically. The presence of right upper quadrant or epigastric abdominal pain is concerning for liver swelling and potential rupture. Severe thrombocytopenia may predispose the patient to bleeding problems and may be an indication for delivery. Platelet transfusion may be necessary if signs of coagulation problems are evident clinically, if the platelet count is < 20,000 mm3, or if a surgical procedure is planned. If the pregnancy is more than 34 weeks of gestation in a well-dated pregnancy, there is no benefit to delaying delivery once the mother’s condition is stabilized.7 Delivery should take place in a facility that can provide neonatal support if necessary.

Severe preeclampsia is not a contraindication to a vaginal delivery. Vaginal delivery, however, is not recommended in pregnancies less than 30 weeks gestation with HELLP syndrome and a Bishop score of less than 5.8 Pitocin (Oxytocin) or prostaglandins may be used to induce labor. Epidural anesthesia for labor is not contraindicated unless severe thrombocytopenia is present. After delivery, the disease process usually begins to improve quickly. Within the first 48 hours, many laboratory values will have begun to return to normal, urinary output should have increased dramatically, and the proteinuria usually will have diminished significantly. In spite of these improvements, seizures can still occur up to 48 hours after delivery. Magnesium sulfate should be continued for the first 24 hours postpartum or until the patient has demonstrated a significant and sustained diuresis. It may be continued longer if neurologic symptoms persist and there is ongoing concern for seizure. If HELLP syndrome was a complicating factor, those laboratory abnormalities should be followed until they begin to show improvement. Hypertension may persist after delivery for several weeks to months and may require ongoing treatment.

Management Remote from Term

Pregnancies complicated by severe preeclampsia remote from term pose more difficult clinical decisions. In these pregnancies, the desire to delay the delivery in hopes of improving the fetal outcome is understandable. Expectant management has been advocated by some authors in those pregnancies with severe preeclampsia and less than 34 weeks of gestation where the mother can be safely stabilized and there is no evidence of fetal compromise. The immediate goal of expectant management is to delay delivery for 24 to 48 hours in order to give antenatal steroids to improve fetal lung function. Longer delays may have other benefits to the fetus, especially in the case of the extremely premature infant. In a retrospective study by Sibai and others, expectant management resulted in prolonging pregnancies between 27 and 33 6/7 weeks’ gestation by a median of 5 days. While the neonatal outcomes were favorable, maternal morbidity was seen in 25% of mothers.9 Conditions such as pulmonary edema, renal failure, eclampsia, DIC, or nonreassuring fetal status necessitate delivery at any gestational age once the patient is stabilized. Previable pregnancies or pregnancies at the edge of viability which are complicated by severe preeclampsia pose even more difficult moral and ethical decisions. Again, maternal well-being must be the first consideration in these difficult cases and early termination of the pregnancy may be indicated.

Complications

Much like the disease itself, the complications of severe preeclampsia are protean in nature. Complications commonly listed include pulmonary edema, renal failure, DIC, abruptio placentae, adult respiratory distress syndrome, subcapsular liver hematoma, and retinal detachment (see Table 17-1). All of these complications are more common in pregnancies complicated by HELLP syndrome. Maternal deaths are still encountered as a result of eclamptic seizures, liver rupture, or cerebral vascular accidents. Fetal and neonatal morbidity and mortality result from intrauterine growth restriction, preterm delivery, and complications associated with placental abruptions. Patients in whom preeclampsia is diagnosed early in gestation have a higher complication rate. Future pregnancies may also be complicated by preeclampsia.10

The syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) deserves special consideration as this syndrome adds to the complexity of severe preeclampsia. The acronym of HELLP was coined by Weinstein in 1985, but Pritchard and others had described many features of the syndrome much earlier.11,12 While this syndrome is usually associated with the typical features of preeclampsia, 10% to 15% of patients with HELLP syndrome will lack proteinuria or hypertension.13 The hemolysis is due to a microangiopathic hemolytic process. The elevated liver enzymes are the result of liver ischemia and periportal necrosis. The thrombocytopenia is variable and related to platelet activation, aggregation, and consumption. Diagnostic tests for these problems include evaluation of liver enzymes (AST and ATL), a CBC and platelet count, and an LDH level. Some or all of these changes may be diagnosed in the individual patient. The clinical course is usually progressive and is associated with increased rates of maternal and fetal morbidity and mortality. Thrombocytopenia is a particularly worrisome development that predisposes the patient to significant risks. The development of a subcapsular liver hematoma and subsequent rupture often has devastating consequences. Special care and expertise are often needed to manage these very difficult cases. The abnormalities resolve fairly quickly after delivery and usually without permanent organ damage. Women with a history of HELLP syndrome have an increased risk of preeclampsia in their subsequent pregnancies, especially if the onset of the disease was in the second trimester.14

aThis study included women with previous preeclampsia.The other studies included only nulliparous women.

bThese rates are for delivery at less than 34 weeks.

Comprehension Questions

17.1 Which of the following is a criteria for the diagnosis of severe preeclampsia?

A. Presence of 3+ edema

B. Maternal blood pressure > 160/110 mm Hg on two separate occasions

6 hours apart

C. The excretion of 700 mg of protein in a 24-hour urine collection

D. Decreased fetal movement

17.2 A 22-year-old G1P0 woman at 29 weeks’ gestation is noted to have a diagnosis of HELLP syndrome. Which of the following finding is most likely to be present in this patient?

A. Seizures/convulsions

B. Oliguria

C. Low platelets

D. Subcapsular liver hematoma

17.3 Magnesium sulfate is given to the preeclamptic patient for which of the following?

A. Control blood pressure

B. Improve urinary output

C. Reduce peripheral edema

D. Prevent seizures

17.4 A 28-year-old nullipara at 29 weeks’ gestation is diagnosed with severe preeclampsia based on persistent blood pressures of 220/140 mm Hg range and 3+ proteinuria. Her first-trimester blood pressures were in the 100/60 mm Hg range. She is counseled regarding the risks and benefits of expectant management versus delivery. Which of the following statement is most accurate for this patient?

A. Delivery is generally not indicated until after 34 weeks of gestation.

B. Delivery is generally performed for the benefit of the mother.

C. Expectant management is associated with a higher rate of maternal complications.

D. Control of the blood pressures with antihypertensive agents are associated with improved fetal outcome.

ANSWERS

17.1 B. The diagnosis of severe preeclampsia is most often made in the presence of severe hypertension (systolic blood pressure of > 160 mm Hg and diastolic blood pressure > 110 mm Hg) and significant proteinuria (> 5 g of urinary protein per 24 h urine collection). By definition, the severe hypertension should be persistent and seen on two readings 6 hours apart. While the presence of significant edema may be present in the severely preeclamptic patient, it is not part of the diagnostic criteria. The same may be said for decreased fetal movement.

17.2 C. The diagnostic criteria for HELLP syndrome include hemolysis, elevated liver enzymes, and low platelets. The preeclamptic patient with HELLP syndrome may have oliguria and is at risk for a subcapsular liver hematoma, but these are complications of her disease, not part of the diagnostic criteria. Eclampsia is, by definition, a seizure in a preeclamptic patient.

17.3 D. Magnesium sulfate is given for seizure prophylaxis only. It may lower the blood pressure slightly but other drugs should be used to treat severe hypertension. Magnesium sulfate therapy frequently reduces urinary output; therefore urine production should be closely monitored. Magnesium sulfate does not help in reducing peripheral edema.

17.4 B. Expectant management of the patient with severe preeclampsia only benefits the fetus. There are no maternal benefits, only a higher risk of maternal complications. Expectant management should only be considered for the fetus less than 34 weeks’ gestation. Most authorities feel that after 34 weeks of gestation there are few benefits to further delay. While expectant management may reduce the risk of some complications of prematurity to the fetus, there is no guarantee that complications related to prematurity will not occur.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ Severe preeclampsia by proteinuria alone is not an indication for delivery (Level II-2).

➤ Eclampsia may be seen only in patients who slighted elevated blood pressures (Level III).

➤ Magnesium sulfate is not a CNS depressant for the mother or the fetus (Level II-1).

➤ A persistent headache and abdominal pain are clinical signs of worsening disease (Level III).

➤ Urine dipstick testing for protein has a poor predictive value and a high false-positive rate (Level II-2).

➤ Calcium gluconate 1 g IV should be given to reverse toxicity symptoms of magnesium sulfate (Level II-1).

➤ Methergine for control of postpartum bleeding/hemorrhage is contraindicated in the preeclamptic patient (Level III).

➤ The use of antenatal corticosteroids may result in a temporary improvement in abnormal laboratory values of HELLP syndrome (Level II-2).

REFERENCES

1. American College of Obstetricians and Gynecologists. Diagnosis and management of preeclampsia and eclampsia, ACOG Practice Bulletin, No. 33. 2002;33. 

2. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003;102:181. 

3. Williams W J. Complications resulting directly from pregnancy. In: Obstetrics. New York and London: D. Appleton and Co.; 1903:455-466. 

4. Sibia B, Dekker G, Kupferminc M. Preeclampsia. Lancet. 2005;365:785-799. 

5. Barton J, Sibai B. Prediction and prevention of recurrent preeclampsia. Obstet Gynecol. 2008; 112:359-372. 

6. Sibai M. Imitators of Severe Pre-eclampsia. Semin Periantol. 2009;33:196-205. 

7. Royal College of Obstetricians and Gynaecologists. The Management of Severe Pre-eclampsia/Eclampsia. Guideline No.10 (A), March 2006. 

8. Gabbe SG, Niebyl JR, Simpson JL. Preeclampsia. In: Obstetrics: Normal and Problem Pregnancies. 5th ed. New York, NY: Churchill Livingstone; 2007:866-890. 

9. Bombrys AE, Barton JR, Hable M, Sibai BM. Expectant management of severe preeclampsia at 27 0/7 to 33 6/7 weeks’ gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management. Am Journ Perinatol. 2009;26:441-446. 

10. Sibai BM, El-Nazer A, Gonzalez-Ruiz AR. Severe preeclampsia-eclampsia in young primigravid women: subsequent pregnancy outcome and remote prognosis. Am J Obstet Gynecol. 1986;155:1011. 

11. Weinstein L. Preeclampsia-eclampsia with hemolysis, elevated liver enzymes, and thrombocytopenia. Obstet Gynecol. 1985;66:657. 

12. Pritchard JA, Weisman R J, Ratnoff OD, et al. Intravascular hemolysis, thrombocytopenia and other hematologic abnormalities associated with severe toxemia of pregnancy. N Engl J Med. 1954;250:87. 

13. Martin JN, Rinehart B, May WL, et al. The spectrum of severe preeclampsia: comparative analysis by HELLP syndrome classification. Am J Obstet Gynecol. 1999;180:1373. 

14. Van Pampus MG,Wolf H, Mayruhu G, et al. Long-term follow-up in patients with a history of (H)ELLP syndrome. Hypertens Pregnancy. 2001;20:15. 

15. Hauth JC, Ewell MG, Levine RJ, et al. Pregnancy outcomes in healthy nulliparas who developed hypertension. Obstet Gynecol 2000;95(1):24-8. 

16. Buchbinder A, Sibai, Caritis S, et al. Adverse perinatal outcomes are signifcantly higher in severe gestational hypertension than in mild preeclampsia. Am J Obstet Gynecol 2002;186(1):66-71. 

17. Hnat MD, Sibai BM, Caritis S, et al. Perinatal outcome in women with recurrent preeclampisa compared wtih women who developed preeclampsia as nulliparas. Am J Obstet Gynecol 2003;189(1):244.

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