Clinical Management of the Preeclampsia Syndrome
BS. Nguyễn Hồng Anh
Preeclampsia remains one of the leading causes of death and severe maternal morbidity. This chapter discusses many clinical aspects of the preeclampsia syndrome and its management after recognition. Also presented are the long-term consequences that may accrue in affected women. The pathophysiology of preeclampsia was detailed in Chapter 40.
DIAGNOSIS AND EVALUATION
■ Diagnosis
In routine prenatal care, gravidas are seen more often during the third trimester, and this aids early detection of preeclampsia. However, it cannot always be diagnosed definitively. Increases in systolic and diastolic blood pressure can be either normal physiological changes or signs of developing pathology. Women without overt hypertension, but in whom the early development of preeclampsia is suspected, are seen more frequently. Heightened surveillance permits recognition of ominous changes in blood pressure, critical laboratory findings, and clinical signs and symptoms. Outpatient surveillance continues unless overt hypertension, proteinuria, headache, visual changes, or epigastric pain supervene. At Parkland Hospital, women with new-onset overt hypertension—either diastolic pressures ≥90 mm Hg or systolic pressures ≥140 mm Hg— are admitted to exclude preeclampsia or to define its severity.
■ Evaluation
With hospitalization, a systematic evaluation begins:
• Detailed examination, which is coupled with daily scrutiny for headache, visual changes, or epigastric pain
• Daily weight measurement to identify rapid weight gain
• Quantification of proteinuria or a urine protein: creatinine ratio
• Blood pressure readings with an appropriate-size cu every 4 hours, unless previously elevated, which would manate more frequent readings
• Measurements of serum creatinine an hepatic transaminase levels an a hemogram that inclues a platelet count. The frequency o testing is etermine by hypertension severity. Although some recommen assessment o serum uric aci an lactate ehyrogenase levels an coagulation, their value has been questione (Chescheir, 2019; Cone-Aguelo, 2015)
• Evaluation o etal size an well-being an amnionic ui volume
• Reuce physical activity may have benets, although evi- ence is not robust. Still investigational as a clinical tool, measurements o placental growth actor (PlGF) an soluble ms-like tyrosine kinase 1 (sF1t-1) levels will likely be available to help preict preeclampsia (Barton, 2020; Chappell, 2013; Zeisler, 2016). Chapter 40 (p. 694) escribes their role in preeclampsia genesis.
In sum, evaluation goals are early ientication o preeclampsia an then management until timely elivery. Complete abatement o all signs an symptoms is uncommon until ater elivery. I severe preeclampsia is iagnose using the criteria in able 40-2 (p. 690), urther management is subsequently escribe.
■ Consideration for Delivery
With gestational hypertension, its morbidity and management vary depending on hypertension severity, presence of preeclampsia, and gestational age of the fetus. The basic management objectives for any pregnancy complicated by preeclampsia are: (1) termination of pregnancy with the least possible trauma to mother and fetus, (2) birth of a healthy newborn that subsequently thrives, and (3) complete restoration of health to the mother. In many with preeclampsia, especially those at or near term, all three objectives are served equally well by induction of labor. Termination of pregnancy is the only known cure for preeclampsia. Headache, visual changes, or epigastric pain are indicative that convulsions may be imminent, and oliguria is another ominous sign. Severe preeclampsia almost always demands anticonvulsant and antihypertensive therapy, followed by delivery. Treatment for eclampsia is identical. Prime objectives are to orestall convulsions, control blood pressure to prevent intracranial hemorrhage and serious damage to other organs, an eliver a healthy newborn. Tis is true even when the cervix is unfavorable. Labor induction is carrie out, usually with preinuction cervical ripening (Chap. 26, p. 488).
Concerns stemming rom an unavorable cervix, a perceive sense o urgency because o preeclampsia severity, an a nee to coorinate neonatal intensive care have le some to avocate or cesarean elivery. In an earlier stuy rom Parklan Hospital, Alexaner an colleagues (1999) reviewe 278 singleton liveborn neonates weighing 750 to 1500 g elivere o women with severe preeclampsia. In hal o the women, labor was inuce, an inuction was successul in accomplishing vaginal elivery in a thir. Similar ata were reporte rom the Consortium on Sae Labor (Coviello, 2019). In this stuy, hal o 914 women with severe preeclampsia unerwent inuction, an hal o these were elivere vaginally. Others have reporte similar observations (Alanis, 2008; Rolan, 2017). For these reasons, we attempt labor inuction an reserve cesarean elivery or other obstetrical inications.
With preeclampsia without severe eatures, optimal elivery timing has not been wiely stuie. A ranomize trial o 756 women with mil preeclampsia supporte elivery ater 37 weeks’ gestation (Koopmans, 2009). Tis practice is also supporte by the American College o Obstetricians an Gynecologists (2020a). At Parklan Hospital, we eliver women with preeclampsia without severe eatures at 38 weeks’ gestation.
With a preterm etus, the tenency is to elay elivery to help reuce the risk o neonatal eath or serious morbiity rom prematurity. Such a policy certainly is justie in miler cases. Assessments o etal well-being an placental unction are perorme, especially when the etus is immature. o assess these, most recommen requent perormance o nonstress testing or biophysical proles, which are escribe in Chapter 20 (p. 392). Te American College o Obstetricians an Gynecologists (2021a,b) recommens consieration or antenatal surveillance twice weekly or those with gestational hypertension an nonsevere eatures an aily testing or those with severe eatures.
With late-preterm etuses, that is, those between 34 an 36 weeks’ gestation, the ecision to eliver is less clear (Barton, 2011; Langenvel, 2011). Te Dutch HYPIA-II stuy ran- omly assigne women with nonsevere hypertension between 34 an 37 weeks to immeiate elivery or to expectant management (Broekhuijsen, 2015). Immeiate elivery reuce the risks or averse maternal outcomes—1.1 versus 3.1 percent.
However, it increase the risk or neonatal respiratory istress synrome— 5.7 versus 1.7 percent. In a more recent stuy, 901 women at 34 to <37 weeks’ gestation with nonsevere preeclampsia were ranomly assigne to early elivery or expectant management (Chappell, 2019). A thir o each group sel-stratie into intervals o 34, 35, an 36 weeks’ gestation. For women in the immeiate elivery group, rates o the primary maternal outcomes, which were eatures o severe preeclampsia, were signicantly lower than in the expectant group. Conversely, rates o averse perinatal outcomes, which were perinatal eaths or neonatal unit amission, were signicantly greater in the immeiate elivery group. Similar nings were reporte by other (Bernares, 2019; Chatzakis, 2021). Last, the PEACOCK stuy oun that angiogenic biomarkers i not help etermine the nee or elivery in latepreterm preeclampsia (Duhig, 2021). At Parklan Hospital, we avor an active management approach given the maternal risks o expectant management. However, i preeclampsia is nonsevere, we routinely inuce ater 38 complete weeks.
■ Inpatient or Outpatient Care
For women with mil to moerate stable hypertension, whether or not preeclampsia has been conrme, monitoring is continue. During surveillance, reuce physical activity throughout much o the ay, at least intuitively, seems reasonable. Complete be rest was not recommene in the prior consensus work o the American College o Obstetricians an Gynecologists’ ask Force on Hypertension in Pregnancy (2013). Also, the Society or Maternal-Fetal Meicine (2020b) suggests that activity restriction not be prescribe or women with hypertensive isorers. Complete be rest is pragmatically unachievable because o the severe restrictions it places on otherwise well women. It likely also preisposes to thromboembolism (Knight, 2007; McCarty-Singleton, 2014).
o reuce activity, several stuies have aresse the benets o inpatient care an outpatient management. Te concept o prolonge hospitalization or women with hypertension arose uring the 1970s. At Parklan Hospital, an inpatient antepartum unit was establishe in 1973 by Dr. Peggy Whalley to provie care or such women. Initial results rom this unit were reporte by Hauth (1976) an Gilstrap (1978) an their coworkers. Most hospitalize women have a benecial response characterize by amelioration or improvement o hypertension. Tese women are not “cured,” and nearly 90 percent have recurrent hypertension beore or during labor. By 2020, more than 10,000 nulliparas with mil to moerate, early-onset hypertension uring pregnancy ha been manage successully in this unit. Tis relatively simple unit requires moest nursing care, no rugs other than iron an olate supplements, an ew essential laboratory tests. Provier costs— not charges—or this care are minimal compare with the cost o neonatal intensive care or a preterm neonate. Importantly, thromboembolic isease has been rare in these women. Many clinicians believe that urther hospitalization is not warrante i hypertension abates within a ew ays, an this has embolene thir-party payers to eny inpatient reimbursement.
Consequently, many women with mil to moerate hypertension are manage at home. For women in vulnerable socioemographic home situations, this strategy may not be easible. In other groups, outpatient management may continue as long as preeclampsia synrome oes not worsen an etal jeopary is not suspecte. Decrease activity is recommene, an women are encourage to report symptoms. Home bloo pressure an urine protein monitoring or requent evaluations by a visiting nurse may be benecial.
o assess this approach, 1182 nulliparas with mil gestational hypertension—20 percent ha proteinuria—were manage with home care (Barton, 2002). Teir mean gestational ages were 32 to 33 weeks at enrollment an 36 to 37 weeks at elivery. Severe preeclampsia evelope in approximately 20 percent, two women ha eclampsia, an 3 percent evelope hemolysis, elevate liver enzyme levels, an low platelet count (HELLP) synrome. Perinatal outcomes were generally goo.
In approximately 20 percent, etal growth was restricte, an the perinatal mortality rate was 4.2 eaths in 1000 births.
Table 41-1 presents two stuies that compare continue hospitalization an outpatient care. In the rst trial, ater hospital evaluation, 218 women with mil gestational nonproteinuric hypertension were ranomly assigne to continue hospitalization versus home care (Crowther, 1992). Te mean hospitalization uration was 22.2 ays or women with inpatient management compare with only 6.5 ays in the home care group. Severe hypertension an preterm elivery beore 34 an beore 37 weeks’ gestation were signicantly increase twool in the outpatient group. Despite this, maternal an newborn outcomes were otherwise similar.
Another approach, popular in Europe, is ay care. In the secon trial (able 41-1), 374 women with gestational hypertension were ranomize to either ay care or inpatient care (urnbull, 2004). Almost 95 percent ha mil to moerate hypertension an 86 women ha ≥1+ proteinuria. Tere were
no perinatal eaths, an none o the women evelope eclampsia or HELLP synrome. Costs or either scheme were not signicantly ierent, an general satisaction avore ay care.
In sum, either inpatient or close outpatient management
is appropriate or a woman with mil e novo hypertension,
incluing those with nonsevere preeclampsia. Keys to success
are close surveillance an patients with home support an
access to care.
■ Antihypertensive Therapy for Mild to Moderate Hypertension
Antihypertensive rugs have been evaluate to prolong pregnancy or moiy perinatal outcomes in pregnancies complicate by various hypertensive isorers. reatment or women with chronic hypertension complicating pregnancy is iscusse in Chapter 53 (p. 949). Drug treatment or early mil preeclampsia has been isappointing (Table 41-2). Sibai an associates (1987a) reporte that women given labetalol ha signicantly lower mean bloo pressures than those given a placebo. However, mean pregnancy prolongation, gestational age at elivery, an birthweights i not ier between groups.
Te cesarean elivery rate an the number o newborns amitte to special-care nurseries also were similar. Te requency o growth-restricted neonates was doubled in women given labetalol compared with placebo—19 versus 9 percent.
Te three other stuies liste in able 41-2 compare labetalol or a calcium-channel blocker rugs against placebo. Except or ewer episoes o severe hypertension, none o these stuies showe any benets rom antihypertensive treatment (Magee, 2015). One review o 49 ranomize trials o antihypertensive therapy or mil to moerate gestational hypertension compare with either no treatment or placebo reache similar conclusions (Abalos, 2014).
■ Expectant Management of Preterm
Severe Preeclampsia
Up through the early 1990s, women with severe preeclampsia were usually immeiately elivere. Subsequently, however, another approach or women with preterm severe preeclampsia was stuie. Te aim o “expectant” management was to improve neonatal outcome without compromising maternal saety. Tis approach always inclues careul aily—an usually more requent—inpatient monitoring o the mother an her etus.
Teoretically, antihypertensive therapy has potential application when severe preeclampsia evelops beore intact neonatal survival is expecte. Such management has been controversial an is potentially angerous (Churchill, 2018). In one o the rst stuies, Sibai an the Memphis group (1985) attempte to prolong pregnancy because o etal immaturity in 60 women with severe preeclampsia between 18 an 27 weeks. Te results were disastrous. Te perinatal mortality rate was 87 percent.
Although no mothers ie, 13 suere placental abruption, 10 ha eclampsia, three evelope renal ailure, two ha hypertensive encephalopathy, one ha an intracerebral hemorrhage, an another ha a rupture hepatic hematoma. Because o their early stuy, the Memphis group reene criteria an perorme a ranomize trial o aggressive versus expectant management or 95 women who ha severe preeclampsia but with more avance gestations o 28 to 32 weeks (Sibai, 1994). Women with HELLP syndrome were excluded rom this trial. Aggressive management inclue glucocorticoi aministration or etal lung maturation ollowe by elivery in 48 hours. Expectantly manage women were observe at be rest an given either labetalol or nieipine orally or severe hypertension. In this stuy, pregnancy was prolonge or a mean o 15.4 ays in the expectant management group. An overall improvement in neonatal outcomes also was reporte.
In women expectantly manage at 23 to 34 weeks’ gestation, serious complications have inclue placental abruption, HELLP synrome, pulmonary eema, renal ailure, an eclampsia (Table 41-3). Moreover, perinatal mortality rates average 90 per 1000 births. Fetal-growth restriction was common, an in stuies rom Te Netherlans, it was an astoun- ing 94 percent (Ganzevoort, 2005a,b). Perinatal mortality rates were isproportionately high in these growth-restricte neonates (Haa, 2007; Shear, 2005).
Following these experiences, expectant management became more commonly practice, with the caveat that women with HELLP synrome or growth-restricte etuses were usually exclue. More recently, a prospective comparative stuy reporte that expectant management o women with “stable” HELLP synrome at <34 weeks may benet mother an etus (Cavaignac-Vitalis, 2019). Te MEXPRE Latin Stuy was a multicenter trial that ranomly assigne 267 women with severe preeclampsia at 28 to 32 weeks’ gestation to prompt elivery or to expectant management (Vigil-De Gracia, 2013). Te perinatal mortality rate approximate 90 per 1000 in each group, an the composite neonatal morbiity outcome was not improve with expectant management. Conversely, etal-growth restriction—22 versus 9 percent—an placental abruption—7.6 versus 1.5 percent—were signicantly higher in the group manage expectantly.
Churchill an colleagues (2018) perorme a Cochrane Database review o six ranomize trials o interventionist versus expectant care or severe preeclampsia between 24 an 34 weeks. Teir review ha nings similar to those in able 41-3 an suggeste that expectant management was benecial to perinatal outcome. However, ata were insufcient to establish conclusions on maternal health.
■ Expectant Management of Midtrimester
Preeclampsia
Several small stuies have ocuse on expectant management o severe preeclampsia synrome beore 28 weeks’ gestation. In one review o eight such stuies, maternal complications were common among nearly 200 women with severe preeclampsia with an onset <26 complete weeks (Bombrys, 2009). Because no neonates survive when elivere beore 23 weeks, most experts recommen pregnancy termination in these cases. For women with slightly more avance pregnancies, however, the ecision is less clear. For example, at 23 weeks’ gestation, the perinatal survival rate was 18 percent, but long-term perinatal morbiity is yet unknown. For women with pregnancies at 24 to 26 weeks, perinatal survival approaches 60 percent, an it averages almost 90 percent or those at 26 weeks. As shown in Table 41-4, maternal complications—especially HELLP synrome—were commonplace an one mother ie. Perinatal mortality exceee 50 percent. At this time, no comparative stuies attest to perinatal benets o such expectant treatment versus early elivery in the ace o serious maternal complications, which approach rates o 50 percent.
Corticosteroids for Lung Maturation
o enhance etal lung maturation, glucocorticois have been aministere to women with severe hypertension who are remote rom term. reatment oes not seem to worsen maternal hypertension, an a lower incience o respiratory istress an improve etal survival rates have been cite. Tat sai, only one ranomize trial has evaluate corticosterois given to hypertensive women or etal lung maturation. Tis trial inclue 218 women who ha severe preeclampsia between 26 an 34 weeks’ gestation an who were ranomly assigne to betamethasone or placebo aministration (Amorim, 1999). Rates o neonatal complications that inclue respiratory istress, intraventricular hemorrhage, an eath were reuce signicantly when betamethasone was given compare with placebo. On the heavily weighted negative side, there were two maternal deaths and 18 stillbirths. We a these nings to buttress our unenthusiastic acceptance o attempts to prolong gestation in many o these women (Alexaner, 2015; Bloom, 2003).
Corticosteroids to Ameliorate HELLP Syndrome
Several observational stuies have inicate that corticosteroi therapy woul ameliorate acets o the HELLP synrome (AñezAguayo, 2018; Martin, 2016). Subsequently, at least three ran- omize trials aime to evaluate the benets o glucocorticois given to improve the laboratory abnormalities associate with HELLP synrome. Fonseca an associates (2005) ranomly assigne 132 women with HELLP synrome to either examethasone or placebo aministration. Outcomes assesse inclue hospitalization length, recovery time o abnormal laboratory test results, resolution o clinical parameters, an complications that inclue acute renal ailure, pulmonary eema, eclampsia, an eath. None o these was signicantly ierent between the two groups. In another stuy, 105 postpartum women with HELLP synrome were assigne to examethasone or placebo treatment. Katz an colleagues (2008) oun no avantage to examethasone (Fig. 41-1). In the thir stuy, preeclamptic women were given either placebo or methylprenisolone i their platelet count was between 50,000 an 150,000/μL (Pourrat, 2016). Again, no benets were gaine rom corticosteroi therapy. A Bolivian stuy i show benets rom corticosteroi therapy, however, it was not ranomize (Añez-Aguayo, 2018).
Because o these nings, the 2013 ask Force oes not recommen corticosteroi treatment to improve thrombocytopenia with HELLP synrome.
■ Expectant Management Recommendations
aken in toto, these stuies o not show overwhelming benets o expectant management o severe preeclampsia in women with gestations rom 24 to 32 weeks compare with maternal risks. Despite these caveats, the Society or Maternal-Fetal Meicine (2011) has etermine that such management is a reasonable alternative in selecte women with severe preeclampsia beore 34 weeks (Fig. 41-2). Te ask Force (2013) supports this recommenation. As shown in Table 41-5, such management calls or inpatient maternal an etal surveillance with elivery prompte by evience or worsening severe preeclampsia or maternal or etal compromise. Although attempts are mae or vaginal elivery in most cases, the likelihoo o cesarean elivery rises with ecreasing gestational age.
Our view is more conservative. Unoubtely, the overri- ing reason to terminate pregnancies with severe preeclampsia is maternal saety. Inee, it seems obvious that a elay to prolong gestation in women with severe preeclampsia may have serious maternal consequences. Tese observations are even more pertinent when consiere with the absence o convincing evience that perinatal outcomes are markely improve by the average prolongation o pregnancy by approximately 1 week. I unertaken, the caveats that manate elivery shown in able 41-5 shoul be strictly heee.
■ Experimental Therapies
In preliminary stuies, therapies have been use to lower serum levels o antiangiogenic actors in hopes to mitigate their averse actions. Some o these inclue therapeutic apheresis to lower sFlt-1 levels (Tahani, 2016; Winkler, 2018). Another novel therapy uses RNA molecules to silence placental sFlt-1 (uranov, 2018). Te proton-pump inhibitor esomeprazole was stuie in women with early-onset preeclampsia (Cluver, 2018). Sildenafl citrate, a phosphoiesterase inhibitor, has been provie to promote vasoilation (rapani, 2016; Vigil-De Gracia, 2016).
Other stuies compare recombinant antithrombin inusion with placebo (Paias, 2020). In general, none o these therapies has shown promise.
SEVERE PREECLAMPSIA AND ECLAMPSIA
Classication o preeclampsia with severe eatures is summarize in able 40-2 (p. 690). Briey, eatures inclue systolic bloo pressure ≥160 mm Hg or iastolic pressure ≥110 mm Hg; liver erangement with transaminitis; thrombocytopenia; renal insufciency; pulmonary eema; new-onset heaache; or visual changes. Eclampsia is ene by new-onset tonic-clonic, ocal, or multiocal seizures in the absence o other causes.
■ Eclampsia
Te evelopment o eclampsia appreciably raises the risk to mother an etus (Fishel-Bartal, 2020). In an earlier report, Mattar an Sibai (2000) escribe outcomes in 399 consecutive women with eclampsia rom 1977 through 1998. Major maternal complications inclue placental abruption—10 percent, neurological ecits—7 percent, aspiration pneumonia—7 percent, pulmonary eema—5 percent, cariopulmonary arrest— 4 percent, an acute kiney injury (AKI)—4 percent. Moreover, 1 percent o these women ie. Several subsequent reports similarly escribe excessive maternal morbiity an mortality rates with eclampsia that also inclue HELLP synrome, pulmonary embolism, an stroke (Anersgaar, 2006; Knight, 2007).
Almost without exception—but at times unnotice— preeclampsia precees convulsions. Eclampsia is most common in the last trimester an becomes increasingly requent as term approaches. Postpartum, the incience o eclampsia has ecline uring the past ecae. Improve access to prenatal care, earlier etection o antepartum preeclampsia, an prophylactic use o magnesium sulate are explanations (Chames, 2002). Other iagnoses shoul be consiere in women with convulsions more than 48 hours postpartum or in women with ocal neurological ecits, prolonge coma, or atypical eclampsia.
■ Clinical Findings with Eclampsia
Eclamptic seizures may be violent, an the woman must be protecte, especially her airway. So orceul are the muscular movements that the woman may throw hersel out o her be, an i not protecte, her tongue is bitten by the violent action o the jaws (Fig. 41-3). Tis phase, in which the muscles alternately contract an relax, may last approximately a minute. Graually, the muscular movements become smaller an less requent, an nally the woman lies motionless. Ater a seizure, the woman is postictal, but in some, a coma o variable uration ensues. When the convulsions are inrequent, the woman usually recovers some egree o consciousness ater each attack. As the woman arouses, a semiconscious combative state may ensue. In severe cases, coma persists rom one convulsion to another, an eath may result.
Rarely, a single convulsion may be ollowe by coma rom which the woman may never emerge. As a rule, however, eath oes not occur until ater requent convulsions. Last, an also rarely, convulsions continue unabate—status epilepticus—an require eep seation an even general anesthesia to obviate anoxic encephalopathy.
Te respiratory rate ater an eclamptic convulsion usually rises an may reach 50 or more per minute in response to hypercarbia, lactic aciemia, an transient hypoxia. Cyanosis may be observe in severe cases. High ever is a grave sign as it likely emanates rom cerebrovascular hemorrhage.
Proteinuria is usually present, an a ourth o women with severe preeclampsia have some egree o AKI (Roriguez, 2021).
Urine output may be iminishe appreciably, an occasionally anuria evelops. Hemoglobinuria may be seen, but hemoglobinemia is rare. Eema may be pronounce (Fig. 41-4). With severe preeclampsia, urinary output rises ater elivery an is usually an early sign o improvement. With renal ysunction, serum creatinine levels are serially monitore.
Proteinuria an eema orinarily isappear within a week postpartum. In most cases, bloo pressure returns to normal within a ew ays to 2 weeks ater elivery (Berks, 2009). As subsequently iscusse, persisting an severe hypertension likely pre- icts unerlying chronic vascular isease.
In antepartum eclampsia, labor may begin spontaneously shortly ater convulsions ensue an may progress rapily. I the seizures evelop uring labor, contractions may increase in requency an intensity, an the uration o labor may be shortene. Because o maternal hypoxemia an lactic aciemia cause by convulsions, etal braycaria oten ollows a seizure (Fig. 41-5). In our experiences, the etal heart rate usually recovers within 2 to 10 minutes. I it persists more than 10 minutes, another cause o braycaria, such as placental abruption, shoul be consiere.
Pulmonary eema may ollow shortly ater eclamptic convulsions or several hours later. Tis complication is urther explore on page 724.
Occasionally, suen eath occurs synchronously with an eclamptic seizure, or it ollows shortly thereater. Most oten in these cases, a massive cerebral hemorrhage is the cause (Fig. 40-11, p. 700). Hemiplegia may result rom sublethal hemorrhage. Cerebral hemorrhages are more likely in oler women with unerlying chronic hypertension. For women with a neurological ecit ater an eclamptic seizure, consieration is given or emergent cranial compute tomography (C) scanning. Up to 5 percent o women with eclampsia have altere consciousness, incluing persistent coma, ollowing a seizure. Tis may be ue to extensive cerebral eema, an associate transtentorial herniation may cause eath (Cunningham, 2000). In approximately 10 percent o eclamptic women, some egree o blin- ness ollows a seizure. Te causes o impaire vision which usually improves postpartum, are iscusse in Chapter 40 (p. 701)
Rarely, eclampsia is ollowe by psychosis, an the woman becomes violent. Tis may last or several ays to 2 weeks. Te prognosis or return to normal unction is goo, provie mental illness was not preexisting. It is presume to be similar to postpartum psychosis iscusse in Chapter 64 (p. 1148). Antipsychotic meications have been eective in the ew cases o posteclampsia psychosis treate at Parklan Hospital.
Generally, eclampsia is more likely to be iagnose too requently rather than overlooke. Epilepsy, encephalitis, meningitis, brain tumor, neurocysticercosis, amnionic ui embolism, postural puncture cephalalgia, an rupture cerebral aneurysm uring late pregnancy or in the puerperium may simulate eclampsia. Until other such causes are exclue, however, all pregnant women with convulsions shoul be consiere to have eclampsia. As a pragmatic rule, loaing with magnesium sulate shoul be consiere while alternate iagnoses are explore.
MANAGEMENT OF SEVERE PREECLAMPSIA-ECLAMPSIA
Most eclampsia regimens in the United States adhere to a similar philosophy:
• Control or prevent convulsions using an intravenous loading dose of magnesium sulfate. This is followed by maintenance fosing, usually given intravenously
• Provide intermittent antihypertensive medication to lower dangerously high blood pressure
• Avoid diuretics unless pulmonary edema is obvious; limit intravenous fluid administration unless fluid loss is excessive; and avoid hyperosmotic agents
• Deliver the fetus to resolve preeclampsia.
■ Magnesium Sulfate
This parenterally administered agent is an effective anticonvulsant and avoids producing central nervous system depression. It may be given intravenously by continuous inusion or intramuscularly by intermittent injection (Table 41-6). A thir option is intermittent, intravenous, 2-g injections (Easterling, 2018). Dosages or severe preeclampsia mirror those or eclampsia. Because labor an elivery is a more likely time or seizures to evelop, women with severe preeclampsia or eclampsia usually are given magnesium sulate uring labor an or 24 hours postpartum. In the Unite States, magnesium sulate is almost universally aministere intravenously. O concern, magnesium sulate solutions, although inexpensive to prepare, are not reaily available in all parts o the eveloping worl.
Even i solutions are available, the technology to inuse them may not be. Tus, the rug can be aministere intramuscularly, an this is as eective as intravenous inusion (Pritchar, 1955, 1975, 1984; Salinger, 2013). Magnesium sulate is not given to treat hypertension. Magnesium ion most likely exerts a specic anticonvulsant action on the cerebral cortex. ypically, the mother stops convulsing ater the initial 4-g loaing ose. By an hour or two, she regains consciousness sufciently to be oriente to place an time.
Te magnesium sulate osage regimens presente in able 41-6 usually result in increase plasma magnesium levels. Data rom Brookel an associates (2016) are illustrate in Figure 41-6. When magnesium sulate is given to arrest an eclamptic seizure, up to 15 percent o women will have a subsequent convulsion. I so, an aitional 2-g ose o magnesium sulate in a 20-percent solution is slowly aministere intravenously. In a small woman, this aitional 2-g ose may be use once, but it can be given twice i neee in a larger woman. In only 5 o 245 women with eclampsia at Parklan Hospital was it necessary to use alternative supplementary anticonvulsant meication to control seizures (Pritchar, 1984). For these, a small ose o a short-acting benzoiazepine such as miazolam or lorazepam is given intravenously. Teir prolonge use is avoie because o an associate higher mortality rate rom aspiration pneumonia (Royal College o Obstetricians an Gynaecologists, 2006).
Maintenance magnesium sulate therapy has traitionally been continue or 24 hours ater elivery. For eclampsia that evelops postpartum, magnesium sulate is aministere or 24 hours ater the onset o convulsions. A ew investigators have truncate this therapy uration to 12 hours an reporte no seizures (Anjum, 2016; Ehrenberg, 2006; Kashanian, 2016).
Outcomes have also been reporte when magnesium sulate therapy was stoppe ater elivery (Lumir, 2017; Vigil-De Gracia, 2018). Tese stuies are relatively small, an the abbreviate magnesium sulate regimens nee urther stuy beore being routinely implemente.
Pharmacology and Toxicology
Parenterally aministere magnesium is cleare almost totally by renal excretion, an magnesium clearance rate is approximately a thir o glomerular ltration rate (GFR) etermine by creatinine clearance. Magnesium intoxication is unusual when the GFR is normal or only slightly reuce. Aequate urine output usually correlates with preserve GFR. Tat sai, magnesium excretion is not urine ow epenent, an urinary volume per unit time oes not, per se, preict renal unction. Tus, serum creatinine levels must be measured to confrm a decreased GFR.
Eclamptic convulsions are almost always prevente or arreste by plasma magnesium levels maintaine at 4 to 7 mEq/L, 4.8 to 8.4 mg/L, or 2.0 to 3.5 mmol/L. However, one review o magnesium pharmacokinetics showe that most regimens result in much lower serum magnesium levels (Okusanya, 2016). Tis was especially true i only 1 g/hr was inuse (Yeet, 2017).
Importantly, the obesity epiemic has aecte these observations (Cunningham, 2016). uela an colleagues (2013) escribe our results rom Parklan Hospital with magnesium aministration to obese women. More than 60 percent o women who ha a boy mass inex (BMI) >30 kg/m2 an who were receiving a 2-g/hr ose ha subtherapeutic levels at 4 hours. Tus, most obese women woul require 3 g/hr to maintain eective plasma levels. Tat sai, most currently o not recommen routine magnesium level measurements (American College o Obstetricians an Gynecologists, 2020a; Royal College o Obstetricians an Gynaecologists, 2006). Patellar reexes isappear when the plasma magnesium level reaches 10 mEq/L—approximately 12 mg/L—presumably because o a curariorm action. Tis sign serves to warn o impening magnesium toxicity. When plasma levels rise above 10 mEq/L, breathing weakens. At 12 mEq/L or higher levels, respiratory paralysis an respiratory arrest ollow (Somjen, 1966). reating with calcium gluconate or calcium chloride, 1 g intravenously, coupled with magnesium sulate discontinuation, usually reverses mild to moderate respiratory depression. One o these agents shoul be reaily available whenever magnesium is being inuse. Unortunately, the eects o intravenously aministere calcium may be short-live i a steay-state toxic magnesium level has been reache. For severe respiratory epression an arrest, prompt tracheal intubation an mechanical ventilation are liesaving. Direct toxic eects on the myocarium rom high levels o magnesium sulate are uncommon (Morisaki, 2000).
Because magnesium is cleared almost exclusively by renal excretion, our described dosages o magnesium sulate will become excessive i the GFR is substantially decreased. Te initial 4- or 6-g loaing ose o magnesium sulate can be saely aministere regarless o renal unction. It is important to aminister the stanar loaing ose an not to reuce it. A loaing ose achieves the esire therapeutic level, an the inusion maintains the steay-state level. Tus, only the maintenance inusion rate should be altered or those with a diminished GFR. Renal function is estimated by measuring plasma creatinine. Whenever plasma creatinine levels are >1.0 mg/mL, serial serum magnesium levels are determined to guide the infusion rate (American College o Obstetricians an Gynecologists, 2020a).
Ater a 4-g intravenous ose is aministere uring 15 minutes, mean arterial pressure alls slightly an is accompanie by a 13-percent rise in cariac inex (Cotton, 1986b). Tus,
magnesium lowers systemic vascular resistance an mean arterial pressure. At the same time, cariac output is increase.
Tese nings are coinciental with transient nausea an ushing, an the cariovascular eects persist or only 15 minutes espite continue magnesium inusion. Magnesium-inuce vasoilation is weaker in placental vessels because o iminishe calcium-channel activity (ang, 2018).
Turnau an coworkers (1987) showe that magnesium therapy le to a small but signicant rise in the cerebrospinal ui’s total magnesium concentration. Te magnitue was irectly proportional to the corresponing serum concentration.
Other Effects
Magnesium has anticonvulsant an neuroprotective eects in animal moels. Some propose mechanisms o action inclue: (1) reuce presynaptic release o the neurotransmitter glutamate, (2) blockae o glutamatergic N-methyl-d-aspartate (NMDA) receptors, (3) potentiation o aenosine action, (4) improve calcium buering by mitochonria, an (5) blockage o calcium entry via voltage-gate channels (Arango, 2008; Wang, 2012).
In the uterus, relatively high serum magnesium concentrations epress myometrial contractility. Inhibition o uterine contractility is magnesium ose epenent, an serum levels o at least 8 to 10 mEq/L are neee to inhibit uterine contractions (WattMorse, 1995). With the suggeste magnesium sulate regimens or seizure prevention, prolonge myometrial epression has not been observe. A transient ecline in activity uring an imme- iately ater the initial intravenous loaing ose can be seen (Leveno, 1998; Witlin, 1997). Bloo loss at elivery is not increase by stanar magnesium sulate treatment (Graham, 2016).
■ Neuroprophylaxis—Prevention of Seizures
Several randomized trials have tested the efficacy of seizure prophylaxis for women with gestational hypertension, with or without proteinuria. In all, magnesium sulfate was superior to the comparator agent to prevent eclampsia. Four of the larger stud- ies are summarized in Table 41-7. In the study from Parkland Hospital, magnesium sulfate therapy was superior to phenytoin to prevent seizures in women with gestational hypertension or preeclampsia (Lucas, 1995). In another study, magnesium sulfate and nimodipine, which is a calcium-channel blocking drug with specific cerebral vasodilator activity, were compared in 1650 women with severe preeclampsia (Belort, 2003). The rate of eclampsia was more than threefold higher for women allocated to the nimodipine group—2.6 versus 0.8 percent.
The largest comparative study was Magnesium Sulfate for Prevention of Eclampsia reported by the Magpie trial Collaboration Group (2002). More than 10,000 women with severe preeclampsia from 33 countries were randomly allocated to treatment with magnesium sulfate or placebo. Women given magnesium had a 58-percent significantly lower risk of eclampsia than those given placebo. Maternal mortality and placental abruption rates also were decreased. Child behavior at 18 months did not differ between groups (Smyth, 2009).
Who Should Be Given Magnesium Sulfate?
Magnesium will prevent proportionately more seizures in women with correspondingly worse disease. However, severity is difficult to quantity, and thus deciding which woman might benefit most from neuroprophylaxis is sometimes diffifcult. The American College of Obstetricians and Gynecologists (2020a) recommends that women with either eclampsia or severe preeclampsia should be given magnesium sulfate prophylaxis. Again, criteria that establish “severity” are not universal. Tus, the conunrum is whether women with “nonsevere” gestational hypertension or preeclampsia shoul receive magnesium neuroprophylaxis. We oun that approximately 1 woman in 100 who has nonsevere preeclampsia but who is not given magnesium sulate prophylaxis can be expecte to have a seizure.
A fourth of these women likely will require emergent cesarean delivery and be exposed to the attendant maternal and perinatal morbidity from general anesthesia. From this, the major question regarding management of nonsevere gestational hypertension remains whether it is acceptable to avoid unnecessary treatment of 99 women to risk eclampsia in one. The answer appears to be yes, as suggested by the American College of Obstetricians and Gynecologists (2020a). At Parkland Hospital, our policy is to give magnesium neuroprophylaxis to women with preeclampsia with severe features, and conservatively to those with proteinuria hypertension (Table 40-1, p. 689).
Fetal and Neonatal Effects
Magnesium administered parenterally promptly crosses the placenta to achieve equilibrium in fetal serum and less so in amnionic fluid (Gortzak-Uzan, 2005; Narasimhulu, 2017). Magnesium sulfate has small but significant effects on the fetal heart rate pattern and specifically on beat-to-beat variability (Hallak, 1999). One study showed a lower baseline heart rate that was within the normal range; Decreased variability; and fewer prolonged decelerations (Duy, 2012).
Overall, maternal magnesium therapy appears safe for perinates (Drassinower, 2015). One study of more than 1500 exposed preterm neonates found no association between the need for neonatal resuscitation and cord blood magnesium levels (Johnson, 2012). Still, a few neonatal adverse events are associated with its use. In a Parkland Hospital study of 6654 mostly term, exposed newborns, 6 percent had hypotonia (Abbassi-Ghanavati, 2012). In addition, exposed neonates had lower 1- and 5-minute Apgar scores, a higher intubation rate, and more admissions to the special care nursery. Neonatal depression occurs only if hypermagnesemia at delivery is severe.
Observational studies suggest a protective effect of magnesium against the development of cerebral palsy in very-lowbirthweight newborns (Crowther, 2017). These beneficial effects may extend to growth-restricted fetuses. Randomized trials have also assessed neuroprotective effects for preterm neonates, and findings are discussed in Chapter 45 (p. 803). One review expanded this possibility to include term newborns, but data were insuficient to draw conclusions (Nguyen, 2013).
Maternal Safety and Efficacy
The multinational Eclampsia trial Collaborative Group study (1995) involved 1687 women with eclampsia randomly allocated to one of three different anticonvulsant regimens: magnesium sulfate, diazepam, or phenytoin (Table 41-8). In aggregate, magnesium sulfate therapy was associated with a significantly lower incidence of recurrent seizures (9.7 percent) compared with women given phenytoin (28 percent) or diazepam (17 percent). Moreover, the aggregate maternal death rate of 3.2 percent with magnesium sulfate was significantly lower than that of 5.2 percent for the other two regimens.
■ Severe Hypertension Treatment
Dangerous hypertension can cause cerebrovascular hemorrhage and hypertensive encephalopathy, and it can trigger eclamptic convulsions. Other complications are placental abruption and congestive heart failure induced by elevated hypertensive aterloa. Studies highlight the importance of treating systolic hypertension when blood pressures are >160 mm Hg (Juy, 2019; Martin, 2005, 2016).
Because o these serious sequelae, the Working Group or the National High Bloo Pressure Eucation Program (2000) an the American College o Obstetricians an Gynecologists (2020a) recommen treatment to lower systolic pressures to a level ≤160 mm Hg an iastolic pressures to ≤110 mm Hg. Lower iastolic pressures can compromise placental perusion.
From other observations, it seems likely that at least hal o serious hemorrhagic strokes associate with preeclampsia are in women with chronic hypertension (Cunningham, 2005; Zokie, 2018). Long-staning hypertension results in evelopment o Charcot–Bouchard aneurysms in the eep penetrating arteries o the lenticulostriate branch o the mile cerebral arteries. Tese vessels supply the basal ganglia, putamen, thalamus, ajacent eep white matter, pons, an eep cerebellum.
Tese unique aneurysmal weakenings preispose these small arteries to rupture uring suen hypertensive episoes. Several rugs are available to rapily lower angerously elevate bloo pressure in women with pregnancy-associate hypertension. Hyralazine, labetalol, an nieipine are recommene as rst-line agents by the American College o Obstetricians an Gynecologists (2020a). Evience supports their value to ecrease stroke risk (Cleary, 2018).
All three agents have equivalent efcacy. Comparative stu- ies o hyralazine an labetalol show similar results (Mable, 1987; Umans, 2015). Hyralazine causes signicantly more maternal tachycaria an palpitations, whereas labetalol more requently leas to maternal hypotension an braycaria. Ran- omize trials that compare nieipine with labetalol oun neither rug enitively superior, but nieipine lowere bloo pressure more quickly (Gainer, 2019; Zuleen, 2019). Both rugs are associate with a reuce requency o etal heart rate accelerations (Cahill, 2013). Last, a stuy comparing nieipine an hyralazine showe similar efcacy (Sharma, 2017).
A ew other generally available antihypertensive agents have been teste in clinical trials but are not wiely use (Umans, 2015). Tese inclue verapamil, nitroglycerin, nitroprussie, ketanserin, nicaripine, an nimoipine (Belort, 2003; Cornette, 2016). Experimental antihypertensive rugs may eventually be useul or preeclampsia treatment (Lam, 2013).
Hydralazine
Tis antihypertensive agent is aministere intravenously or intramuscularly. An initial 5- to 10-mg ose can act as rapily as 10 minutes. I neee, this is ollowe by 10-mg oses at 15- to 20-minute intervals until a satisactory response is achieve (Table 41-9). Although we will aminister a thir ose, the American College o Obstetricians an Gynecologists (2020a) recommens labetalol therapy i severe hypertension persists ater the secon ose. Another regimen continuously inuses hyralazine at a rate o 0.5 to 10 mg/hr.
For higher bloo pressures, the tenency to give a larger initial ose o hyralazine shoul be avoie. Te response to 5- to 10-mg oses cannot be preicte by hypertension severity. Tus, our protocol is to always aminister 5 mg as the initial ose. An averse response to exceeing this initial ose is shown in Figure 41-7. Tis woman ha chronic hypertension complicate by severe superimpose preeclampsia, an hyralazine was injecte more requently than recommene. Her bloo pressure in less than 1 hour roppe rom 270/150 mm Hg to 110/80 mm Hg. Fetal heart rate ecelerations characteristic o uteroplacental insufciency became evient. Decelerations persiste until her bloo pressure was raise with rapi crystalloi inusion. In some cases, this etal response to iminishe uterine perusion may be conuse with placental abruption an may result in unnecessary an potentially angerous emergency cesarean elivery.
Labetalol
Tis eective intravenous antihypertensive agent is an α- an nonselective β-blocker. Some preer its use to hyralazine because o ewer sie eects. Importantly, labetalol is usually not given to asthmatic women. At Parklan Hospital, we give 10 mg intravenously initially. I bloo pressure has not ecline to suitable levels in 10 minutes, 20 mg is given. Te next 10-minute incremental ose is 40 mg an is ollowe by another 40 mg i neee. I a salutary response is not achieve, an 80-mg ose is provie (see able 41-9). Te American College o Obstetricians an Gynecologists (2020a) recommens starting with a 10- to 20-mg intravenous bolus.
I not eective, this is ollowe by 20 to 80 mg every 10 to 30 minutes. I hypertension persists, hyralazine is then given.
Nifedipine
Tis calcium-channel blocking agent is given initially as a 10- to 20-mg oral ose o immeiate release meication. I necessary ater 20 minutes, a 10- to 20-mg oral ose is repeate. With an unsatisactory response, labetalol is provie. Niedipine given sublingually is no longer recommended. Tis route is associate with angerously rapi an extensive eects.
Diuretics
Potent loop iuretics can urther compromise placental per- usion. Immeiate eects inclue reistribution o intravascular volume, which most oten is alreay reuce in severe preeclampsia (p. 724). Tus, beore elivery, iuretics are not use to lower bloo pressure (Zeeman, 2009; Zonervan, 1988). Furosemie or similar rugs are use beore elivery solely to treat pulmonary eema. Discusse on page 725, they may have a role in treatment o postpartum hypertension.
■ Fluid Therapy
Crystalloi solution is aministere routinely at a rate between 60 an 125 mL per hour, unless ui loss is unusual rom vomiting, iarrhea, iaphoresis, or excessive bloo loss. Oliguria is common with severe preeclampsia. Couple with the knowlege that maternal bloo volume is likely constricte compare with that o normal pregnancy, it is tempting to aminister intravenous uis more vigorously. However, controlle, conservative ui aministration is preerre or the typical woman with severe preeclampsia. Tese gravias alreay have excessive extracellular ui that has inappropriately extravasate rom the intravascular compartment. Inusion o large ui volumes enhances the malistribution an thereby elevates the risk o pulmonary an cerebral eema (Sciscioner, 2003; Zinaman, 1985). Tus, or preeclamptic women with anuria, small incremental boluses can be given to maintain urine output above 30 mL/hr. Diminishe intravascular volume rom hemorrhage or ui loss rom vomiting or ever can similarly be replace by graual incremental boluses o crystalloi.
For labor analgesia with neuraxial analgesia, crystalloi solutions are inuse slowly in grae amounts (Chap. 25, p. 479).
Pulmonary Edema
Women with severe preeclampsia who evelop pulmonary eema most oten o so postpartum (Cunningham, 1986, 2012). With pulmonary eema in the eclamptic woman, aspiration o gastric contents, which may be the result o convulsions, anesthesia, or overseation, shoul be exclue. Otherwise, in women with severe preeclampsia, three common causes o pulmonary eema are pulmonary capillary permeability eema, cariogenic eema, or their combination.
First, in women with preeclampsia, both increase capillary permeability an greater extravascular ui oncotic pressure are oun (Brown, 1989; Øian, 1986). I intravenous ui replacement is vigorous, pulmonary congestion can ollow.
Secon, in some women, pulmonary eema may be cause by ventricular ailure rom increase aterloa that results rom severe hypertension. Such pulmonary eema rom ventricular ailure is more common in morbily obese women an in those with chronic hypertension.
Invasive Hemodynamic Monitoring
Knowlege concerning cariovascular an hemoynamic pathophysiological alterations associate with severe preeclampsia–eclampsia has accrue rom stuies one using invasive monitoring an a pulmonary artery catheter (Fig. 40-5, p. 694). wo conitions requently cite as inications are preeclampsia associate with oliguria or with pulmonary eema (Clark, 2010). Somewhat ironically, it is usually vigorous treatment o the ormer that results in most cases o the latter. Te ask Force (2013) recommens against routine invasive monitoring. Tis is best reserve or women with severe preeclampsia an with accompanying cariac isease, renal isease, or both or with reractory hypertension, oliguria, an pulmonary eema. Preliminary ata rom stuies using a noninvasive cardiac monitoring system nee to be verie beore wiesprea clinical application (Lavie, 2018).
■ Plasma Volume Expansion
Because the preeclampsia syndrome is associated with hemoconcentration, some have infused various fluids, starch polymers, albumin concentrates, or combinations to expand blood volume. Older studies escribe serious complications—especially pulmonary edema—with volume expansion (Beneetti, 1985; Sibai, 1987b).
The Amsterdam randomized study reported by Ganzevoort and coworkers (2005a,b) was a well-designed investigation done to evaluate volume expansion. A total of 216 women with severe preeclampsia were enrolled between 24 and 34 weeks’ gestation. The study included women whose preeclampsia was complicated by HELLP syndrome, eclampsia, pulmonary edema, or fetal-growth restriction. In the group randomly assigned to volume expansion, each woman was given 250 mL o 6-percent hydroxyethyl starch infused over 4 hours twice daily. Pregnancy outcomes were compared with a control group, and none of these were significantly different. Importantly, serious maternal morbidity and a substantive perinatal mortality rate accompanied their expectant management.
■ Analgesia and Anesthesia
During the past 25 years, the use o neuraxial analgesia or women with preeclampsia synrome has prove ieal. Ran- omize stuies attest to its saety, an these trials are ully escribe in Chapter 25 (p. 478). Initial problems with neuraxial analgesia inclue hypotension an iminishe uterine perusion cause by sympathetic blockae in preeclamptic women, who alreay have attenuate hypervolemia. However, slow inuction o epiural analgesia with ilute solutions o anesthetic agents counter the nee or rapi inusion o large volumes o crystalloi or colloi to prevent maternal hypotension (Hogg, 1999; Wallace, 1995).
Importantly, epiural blockae avois general anesthesia, in which the stimulation o tracheal intubation may cause su- en severe hypertension. Such bloo pressure spikes can cause pulmonary eema, cerebral eema, or intracranial hemorrhage. Last, tracheal intubation may be particularly ifcult an thus hazarous in women with airway eema ue to preeclampsia (American College o Obstetricians an Gynecologists, 2020b).
Juicious ui aministration is essential in women with severe preeclampsia who receive regional analgesia. Vigorous crystalloi inusion with epiural blockae in women with severe preeclampsia elevates pulmonary capillary wege pressures (Newsome, 1986). Aggressive volume replacement in preeclamptic women raises their risk or pulmonary eema, especially in the rst 72 hours postpartum (Clark, 1985; Cotton, 1986a). Last, most cases o pharyngolaryngeal eema are relate to aggressive volume therapy (Heller, 1983). In sum, general anesthesia, epiural analgesia, or combine spinal-epiural analgesia are acceptable or women severe preeclampsia i steps are taken to ensure a careul approach to the selecte metho. At Parklan Hospital, a gentle bolus is given accompanying epiural placement (Chap. 25, p. 479).
■ Blood Loss at Delivery
Hemoconcentration or lack of normal pregnancy-induced hypervolemia is an almost predictable feature of severe preeclampsia–eclampsia (Fig. 40-7, p. 696) (Zeeman, 2009). These women, who consequently lack normal pregnancy hypervolemia, may poorly tolerate even normal blood loss. Thus, an appreciable fall in blood pressure soon after delivery most often means excessive blood loss and not sudden resolution of vasospasm and endothelial damage. When oliguria follows delivery, the hematocrit should be evaluated frequently to help detect excessive blood loss. If identified, hemorrhage should be treated appropriately by crystalloid and blood transfusion.
■ Persistent Severe Postpartum Hypertension
Postpartum, 8 percent of women develop e novo hypertension (Goel, 2015). At times, controlling severe hypertension may be difficult or intravenous hydralazine or labetalol or oral immediate-release nifedipine are being used repeatedly. In these cases, oral maintenance regimens can be given. Examples include labetalol or another β-blocking agent; nifedipine extended release; amlodipine; or another calcium-channel blocking agent (Sharma, 2017). Women so treated are less likely to require readmission (Stamilio, 2021; Wen, 2019). The Society for Maternal-Fetal Medicine (2020a) has developed a check list for postpartum care of women with hypertensive disorders. Persistent hypertension is likely aggravated by pathological interstitial fluid that is now returning to the intravascular compartment, by underlying chronic hypertension, or by both (Sibai, 2012; an, 2002). Nonsteroidal antiinflammatory drugs do not aggravate postpartum hypertension (Anastasio, 2018; Penel, 2019). In some women with chronic hypertension and left-ventricular hypertrophy, severe postpartum hypertension can cause pulmonary edema from cardiac failure (Cunningham, 1986, 2019; Sibai, 1987a).
Furosemide
Severe hypertension persists epening on the onset an length o extracellular ui mobilization an iuresis. Tus, it seems logical that urosemie-augmente iuresis might serve to hasten bloo pressure control (Ascarelli, 2005). In one ranomize trial o 384 women with hypertensive isorers o pregnancy, a cohort that receive urosemie postpartum ha signicantly lower bloo pressures at 7 ays—6 versus 14 percent—compare with women who receive placebo (Lopes Perigao, 2021). Te nee or antihypertensive treatment to be given at ischarge in the urosemie group also was signicantly reuce. In another ranomize stuy, women with severe postpartum preeclampsia receive nieipine plus urosemie or nieipine alone. Te urosemie regimen signicantly lowere the nee or aitional antihypertensive agents—8 versus 26 percent, respectively (Veena, 2017). Conversely, in one stuy, torsemide ha no signicant benets (Viteri, 2018).
We use a simple metho to estimate excessive extracellular ui. Te postpartum weight is compare with the most recent prenatal weight, either rom the last clinic visit or rom amission or elivery. ypically, soon ater elivery, maternal weight shoul be reuce by at least 10 to 15 pouns epening on newborn an placental weight, amnionic ui volume, an bloo loss. Because o various interventions, especially intravenous crystalloi inusions given with labor epiural analgesia or uring operative vaginal or cesarean elivery, women with severe preeclampsia oten have an immeiate postpartum weight in excess o their last prenatal weight. I this weight increase is associate with severe persistent postpartum hypertension, iuresis with intravenous urosemie can be helpul in controlling bloo pressure.
Thrombotic Microangiopathy
Occasionally, women have an atypical synrome in which severe preeclampsia–eclampsia persists espite elivery. Martin an associates (1995) escribe 18 such women whom they encountere uring a 10-year perio. Tey avocate single or multiple plasma exchange or these women. In some cases, 3 L o plasma was exchange three times beore a response was orthcoming. Tis is a 36- to 45-onor-unit exposure or each patient. Others have escribe plasma exchange perorme in postpartum women with HELLP synrome (Förster, 2002;
Obeiat, 2002). In all o these cases, however, the istinction between HELLP synrome an thrombotic thrombocytopenic purpura or hemolytic uremic synrome was not clear (sai, 2016). In our experiences with more than 55,000 women with gestational hypertension among nearly 500,000 pregnancies care or at Parklan Hospital through 2021, we have encountere very ew women with persistent postpartum hypertension, thrombocytopenia, an renal ysunction who were iagnose as having a thrombotic microangiopathy (Dashe, 1998).
Reversible Cerebral Vasoconstriction Syndrome
Tis is another cause o persistent hypertension, “thunerclap”
heaaches, seizures, an central nervous system nings. Reversible cerebral vasoconstriction syndrome is characterize by iuse segmental constriction o cerebral arteries an may be associate with ischemic an hemorrhagic strokes. Tis synrome has several inciting causes that inclue pregnancy an particularly preeclampsia (Ducros, 2012). It is more requent in women, an long-term sequelae are uncommon. However, in some cases, vasoconstriction may be so severe as to cause cerebral ischemia an inarction (Boitet, 2020). We have encountere only a ew women with a stroke cause by this arteriopathy (Zokie, 2019). Te most appropriate management is unclear (Cho, 2019).
LONG-TERM CONSEQUENCES
■ Future Pregnancies
Women with preeclampsia during an index pregnancy are at risk for hypertensive and other disorders in subsequent pregnancies and later in life (Wang, 2021). In some, but not all women, the risk for hypertension is higher in the first 6 months postpartum (Giorgione, 2021; Muler, 2021). Even in subsequent nonhypertensive pregnancies, women who had preterm preeclampsia have a higher risk for preterm birth and growth-restricted neonates (Connealy, 2014; Palatnik, 2016). Generally, the earlier preeclampsia is diagnosed during the index pregnancy, the greater the likelihood of recurrence. Women with preeclampsia near term had a recurrence risk of 23 percent, but nulliparas diagnosed with preeclampsia before 30 weeks had a recurrence risk as high as 40 percent (Bramham, 2011; Sibai 1986, 1991).
As perhaps expected, women with HELLP syndrome have a substantive risk for recurrence in subsequent pregnancies. Even if HELLP syndrome does not recur with subsequent pregnancies, again incidences of preterm delivery, fetal-growth restriction, placental abruption, and cesarean delivery are increased (Habli, 2009; Malmström, 2020).
■ Cardiovascular Morbidity
The preeclampsia syndrome is also a marker for subsequent long-term cardiovascular morbidity (Table 41-10) (Hamma, 2020; Stuart, 2018; Wang, 2021). Thus, women with hypertension identified during pregnancy should be evaluated during the first several months postpartum. Te Working Group o the NHBPEP (2000) conclue that hypertension attributable to pregnancy shoul resolve within 12 weeks o elivery, an hypertension persisting beyon this time is consiere chronic (Chap. 53, p. 944). Te Magpie rial Follow-Up Collaborative Group (2007) reporte that 20 percent o 3375 preeclamptic women seen at a meian o 26 months postpartum ha hypertension. From one metanaalysis, a 28-percent incience o hypertension was oun within 2 years o eliveries complicate by preeclampsia (Giorgione, 2021). From a Danish registry an ater a mean o almost 15 years, the incience o chronic hypertension was veol higher in those who ha gestational hypertension, ourol greater ater mil preeclampsia, an sixol higher ater severe preeclampsia compare with women without hypertension in pregnancy (Lykke, 2009).
Any hypertension uring pregnancy is a risk marker or car- iovascular morbiity in later lie (Wang, 2021). As shown in ata rom Brouwers an coworkers (2018), the risk is greater in women with recurrent preeclampsia (Table 41-11). In a stuy rom Icelan, the prevalence o ischemic heart isease—24 versus 15 percent, an o stroke—9.5 versus 6.5 percent, were increase in women who ha gestational hypertension compare with normotensive controls (Arnaottir, 2005). In a Sweish population stuy o more than 400,000 women, those with recurrent preeclampsia ha systolic ysunction an a greater incience o ischemic heart isease (Valensise, 2016).
Diastolic ysunction also is more common (Bokslag, 2018). Preeclampsia is also a risk or coronary artery calcication an iiopathic cariomyopathy (Gammill, 2018; White, 2016). Women who have preeclampsia an who evelop chronic hypertension later in lie have an increase ventricular mass inex beore they become hypertensive (Ghossein-Doha, 2013). Last, in at least some women with prior preeclampsia, hypertensive cariovascular pathologies appear to have begun near the time o their own births. A similar phenomenon is associate with preterm birth an with etal-growth isorers.
Other coactors or comorbiities are relate to acquisition o these long-term averse outcomes (Gastrich, 2012; Harskamp, 2007; Hermes, 2012; Spaan, 2012). Tese inclue the metabolic synrome, iabetes, obesity, yslipiemia, an atherosclerosis (Catzov, 2021; Cho, 2019; Kajantie, 2017). Women with pregnancy-associate hypertension are at increase risk or type 2 iabetes (Stuart, 2018). Preeclampsia preisposes or later iabetic retinopathy an retinal etachment (Auger, 2017; Beharier, 2016).
■ Renal Sequelae
Preeclampsia is a marker or subsequent renal isease. Almost 15 percent o women with prior preeclampsia have renal ysunction (Lopes van Balen, 2017). Tis may be relate to AKI associate with preeclampsia (Novotny, 2020; Roriquez, 2021). In a Danish stuy with more than a million women, the chronic renal isease rate was sixol greater in those who ha preeclampsia (Kristensen, 2019). These data need to be considered in light of the findings that 15 to 20 percent of women with preeclampsia who undergo renal biopsy have evidence of chronic renal disease (Chesley, 1978). In another long-term study, women with prior preeclampsia were significantly more likely to be chronically hypertensive—55 versus 7 percent—compared with control women. They also had higher peripheral vascular and renovascular resistance and decreased renal blood flow. These data do not permit conclusions as to cause versus effect (Spaan, 2009).
■ Central Nervous System Sequelae
Eclamptic seizures were once believed to have no significant longterm CNS sequelae. However, this likely is not the case (Bergman, 2021c; Teilen, 2016). Recall that almost all eclamptic women have multifocal areas of perivascular edema, and approximately a fourth also have areas of cerebral infarction (Zeeman, 2004). In several long-term studies in women with severe preeclampsia and eclampsia, white-matter lesions in the brain that followed eclamptic convulsions persist (Aukes, 2009, 2012). Specifically, with magnetic resonance (MR) imaging, 40 percent of women with prior eclampsia had more numerous and larger aggregate white-matter lesions compared with 17 percent of normotensive control women. These white-matter lesions were also found in women with preeclampsia without convulsions (Aukes, 2012). Others found temporal lobe white-matter changes and reduced cortical volume in women with prior preeclampsia (Siepmann, 2017). In some, but not all studies, women with prior eclampsia had subjectively impaired cognitive functioning anf increased risk for dementia (Basit, 2018; Elharram, 2018). They also had a modest increase in the frequency of seizure disorders (Nerenberg, 2017). In another study, women with prior eclampsia had lower vision-related quality of life compared with control women (Wiegman, 2012)
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