Obstentrics_Williams

Obstentrics_Williams. Pulmonary edema may follow shortly after eclamptic convulsions or to several hours later. This up usually is caused by aspiration pneumonitis from gastric-content inhalation during vomiting that frequently accompanies convulsions. In some women, pulmonary edema may be caused by ventricular failure from increased aterload that results from severe hypertension. Both pulmonary edema and hypertension can be further aggravated by vigorous intravenous fluid administration (Dennis, 2012b). Such pulmonary edema from ventricular failure is more common in morbidly obese women and in those with previously unappreciated chronic hypertension. Occasionally, sudden death occurs synchronously with an eclamptic convulsion, or it follows shortly thereafter. Most often in these cases, a massive cerebral hemorrhage is the cause (see Fig. 40-10). Hemiplegia may result from sublethal hemorrhage. Cerebral hemorrhages are more likely in older women with underlying chronic hypertension.


Obstentrics_Williams

Obstentrics_Williams. In approximately 10 percent of eclamptic women, some degree of blindness follows a seizure. The causes of blindness or impaired vision were discussed earlier (p. 724). Blindness with severe preeclampsia without convulsions usually stems from retinal detachment (Vigil-De Gracia, 2011). Conversely, blindness with eclampsia is typically due to occipital lobe edema (Cunningham, 1995). In both instances, however, the prognosis for return to normal function is good and is usually complete within 1 to 2 weeks postpartum. Up to 5 percent of women with eclampsia have substantively altered consciousness, including persistent coma, following a seizure. This is due to extensive cerebral edema, and associated trans tentorial herniation may cause death (p. 723).


Obstentrics_Williams

Obstentrics_Williams. Rarely, eclampsia is followed by psychosis, and the woman becomes violent. This may last for several days to 2 weeks. The prognosis for return to normal function is good, provided there was no preexisting mental illness. It is presumed to be similar to postpartum psychosis discussed in Chapter 61 (p. 1179). Antipsychotic medications have proven efective in the few cases of posteclampsia psychosis treated at Parkland Hospital. Generally, eclampsia is more likely to be diagnosed too frequently rather than overlooked. Epilepsy, encephalitis, meningitis, brain rumor, neurocysticercosis, amnionic fluid embolism, postdural puncture cephalalgia, and ruptured cerebral aneurysm during late pregnancy or in the puerperium may simulate eclampsia. Until other such causes are excluded, however, all pregnant women with convulsions should be considered to have eclampsia.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 40-18 Fetal heart rate tracing shows fetal bradycardia following an intrapartum eclamptic convulsion. Bradycardia resolved and beat-to-beat variability returned approximately 5 minutes following the seizure. • Management of Eclampsia Magnesium sulfate is highly efective to prevent convulsions in women with preeclampsia and to stop them in those with eclampsia. In his review, Chesley (1978) cited observational data by Pritchard and colleagues (1955, 1975) from Parkland Hospital and from his own institution. At that time, most eclampsia regimens in the United States adhered to a similar philosophy, and it is still in use today: 1. Control of convulsions using an intravenously administered loading dose of magnesium sulfate that is followed by a maintenance dose, usually intravenous, of magnesium sulfate 2. Intermittent administration of an antihypertensive medication to lower blood pressure whenever it is considered dangerously high 3.


Obstentrics_Williams

Obstentrics_Williams. Intermittent administration of an antihypertensive medication to lower blood pressure whenever it is considered dangerously high 3. Avoidance of diuretics unless pulmonary edema is obvious, limitation of intravenous luid administration unless fluid loss is excessive, and avoidance of hyperosmotic agents 4. Delivery of the fetus to resolve preeclampsia. • Magnesium Sulfate to Control Convulsions Magnesium sulfate administered parenterally is an efective anticonvulsant that avoids producing central nervous system depression. It may be given intravenously by continuous inusion or intramuscularly by intermittent injection (Table 40-11). The dosages for severe preeclampsia are the same as for eclampsia. Because labor and delivery is a more likely time for convulsions to develop, women with preeclampsia-eclampsia usually are given magnesium sulfate during labor and for 24 hours postpartum.


Obstentrics_Williams

Obstentrics_Williams. In the United States, magnesium sulfate is almost universally administered intravenously. Of concern, magnesium sulfate solutions, although inexpensive to prepare, are not readily available in all parts of the developing world. And even when the solutions are available, the technology to infuse them may not be. herefore, it should not be overlooked that the drug can be administered intramuscularly and that this route is as efective as intravenous administration (Salinger, 20l3). In two reports from India, intramuscular regimens were nearly equivalent in preventing recurrent convulsions and maternal deaths in women with eclampsia (Chowdhury, 2009; lana, 20l3). hese observations comport with earlier ones from Parkland Hospital (Pritchard, 1975, 1984).


Obstentrics_Williams

Obstentrics_Williams. Magnesium suate is not given to treat hypertension. Magnesium most likely exerts a specific anticonvulsant action on the cerebral cortex. Typically, the mother stops convulsing after the initial 4-g loading dose. By an hour or two, she regains consciousness suiciently to be oriented to place and time.


Obstentrics_Williams

Obstentrics_Williams. he magnesium sulfate dosage regimens presented in Table 40-11 usually result in plasma magnesium levels illustrated in Figure 40-19. When magnesium sulfate is given to arrest eclamptic seizures, 10 to 15 percent of women will have a subsequent convulsion. If so, an additional 2-g dose of magnesium sulfate in a 20-percent solution is slowly administered intravenously. In a small woman, this additional 2-g dose may be used once, but it can be given twice if needed in a larger woman. In only 5 of 245 women with eclampsia at Parkland Hospital was it necessary to use alternative supplementary anticonvulsant medication to control convulsions (Pritchard, 1984). For these, an intravenous barbiturate is given slowly. Midazolam or lorazepam may also be given in a small single dose, but prolonged use is avoided because it is associated with a higher mortality rate from aspiration pneumonia (Royal College of Obstetricians and Gynaecologists, 2006).


Obstentrics_Williams

Obstentrics_Williams. TABLE 40-1 1. Magnesium Sulfate Dosage Schedule for Severe Preeclampsia and EclampSia Give 4-to 6-g loading dose of magnesium sulfate diluted in 100 mL of IV fluid administered over 15-20 min Begin 2 g/hr in 100 mL of IV maintenance infusion. Some recommend 1 g/hr Monitor for magnesium toxicity: Assess deep tendon reflexes periodically Some measure serum magnesium level at 4-6 hr and adjust infusion to maintain levels between 4 and 7 mEq/L (4.8 to 8.4 mg/dL) Measure serum magnesium levels if serum creatininen::1.0 mg/dL Magnesium sulfate is discontinued 24 hr ater delivery Give 4 g of magnesium sulfate (MgS04·7H20 USP) as a 20% solution intravenously at a rate not to exceed 1 g/min


Obstentrics_Williams

Obstentrics_Williams. Give 4 g of magnesium sulfate (MgS04·7H20 USP) as a 20% solution intravenously at a rate not to exceed 1 g/min Follow promptly with 109 of 50% magnesium sulfate solution, one half (5 g) injected deeply in the upper outer quadrant of each buttock through a 3-inch-long 20-gauge needle. (Addition of 1.0 mL of 2% lidocaine minimizes discomfort.) If convulsions persist ater 15 min, give up to 2 g more intravenously as a 20% solution at a rate not to exceed 1 g/min. If the woman is large, up to 4 g may be given slowly. Every 4 hr thereater, give 5 g of a 50% solution of magnesium sulfate injected deeply in the upper outer quadrant of alternate buttocks, but only after ensuring that: The patellar reflex is present, Respirations are not depressed, and Urine output the previous 4 hr exceeded 100 mL Magnesium sulfate is discontinued 24 hr after delivery :J01500 250 deficits, prolonged coma, or atypical eclampsia (Sibai,r2012) . 200 • Clinical Findings with Eclampsia


Obstentrics_Williams

Obstentrics_Williams. 200 • Clinical Findings with Eclampsia Eclamptic seizures may be violent, and the woman must be protected, especially her air150 C way. So forceful are the muscular movements J,.. U :L,that the woman may throw herself out of her -0 bed, and if not protected, her tongue is bitten aby the violent action of the jaws (Fig. 40-16). his phase, in which the muscles alternately contract and relax, may last approximately a minute. Gradually, the muscular movements become smaller and less frequent, and finally the woman lies motionless. After a seizure, the woman is postictal, but in some, a coma of variable duration ensues. When the convulsions are infrequent, the


Obstentrics_Williams

Obstentrics_Williams. After a seizure, the woman is postictal, but in some, a coma of variable duration ensues. When the convulsions are infrequent, the Days after treatment woman usually recovers some degree of con sciousness ater each attack. As the woman arouses, a semiconscious combative state may nase (ASn levels in women with HELLP syndrome assigned to receive treatment with dexamethasone or placebo. (Data from Katz, 2008.) with saline aforded the same interval-to-delivery timing (Sibai,r2017).


Obstentrics_Williams

Obstentrics_Williams. Preeclampsia complicated by generalized tonic-clonic convulsions appreciably raises the risk to both mother and fetus. In an earlier report, Mattar and Sibai (2000) described outcomes in 399 consecutive women with eclampsia from 1977 through 1998. Major maternal complications included placental abruption-10 percent, neurological deicits-7 percent, aspiration pneumonia-7 percent, pulmonary edema-5 percent, cardiopulmonary arrest-4 percent, and acute renal failure4 percent. Moreover, 1 percent of these women died. Several subsequent reports similarly described excessive maternal morbidity and mortality rates with eclampsia that also included HELLP syndrome, pulmonary embolism, and stroke (Andersgaard, 2006; Knight, 2007). In he Netherlands, there were three maternal deaths among 222 eclamptic women (Zwart, 2008). Data from Ireland and Australia are similar (O'Connor, 2013; Thornton, 2013). In perspective, this is a thousandfold increase above the overall maternal death rates for these


Obstentrics_Williams

Obstentrics_Williams. women (Zwart, 2008). Data from Ireland and Australia are similar (O'Connor, 2013; Thornton, 2013). In perspective, this is a thousandfold increase above the overall maternal death rates for these countries.


Obstentrics_Williams

Obstentrics_Williams. Almost without exception-but at times unnoticed-preeclampsia precedes the convulsion onset. Eclampsia is most common in the last trimester and becomes increasingly frequent as term approaches. In more recent years, the incidence of postpartum eclampsia has declined. his is presumably related to improved access to prenatal care, earlier detection of antepartum preeclampsia, and prophylactic use of magnesium sulfate (Chames, 2002). Importantly, other diagnoses should be considered in women with convulsions more than 48 hours postpartum or in women with focal neurological ensue. In severe cases, coma persists from one convulsion to another, and death may result. In rare instances, a single convulsion may be followed by coma from which the woman may never emerge. As a rule, however, death does not occur until after frequent convulsions. Finally and also rarely, convulsions continue unabatedstatus epilepticus-and require deep sedation and even general anesthesia to obviate anoxic


Obstentrics_Williams

Obstentrics_Williams. death does not occur until after frequent convulsions. Finally and also rarely, convulsions continue unabatedstatus epilepticus-and require deep sedation and even general anesthesia to obviate anoxic encephalopathy.


Obstentrics_Williams

Obstentrics_Williams. he respiratory rate ater an eclamptic convulsion is usually increased and may reach 50 or more per minute in response to hypercarbia, lactic acidemia, and transient hypoxia. Cyanosis may be observed in severe cases. High fever is a grave sign as it likely emanates from cerebrovascular hemorrhage. Proteinuria is usually, but not always, present as discussed earlier (p. 720). Urine output may be diminished appreciably, FIGURE 40-16 Hematoma of tongue from laceration during an eclamptic convulsion. Thrombocytopenia may have contributed to the bleeding. :s, FIGURE 40-19 Serum magnesium concentration in normotensive and preeclamptic women following a 4-g loading dose of magnesium sulfate and 2 g/h infusion. (Data from Brookfield, 2016.)


Obstentrics_Williams

Obstentrics_Williams. :s, FIGURE 40-19 Serum magnesium concentration in normotensive and preeclamptic women following a 4-g loading dose of magnesium sulfate and 2 g/h infusion. (Data from Brookfield, 2016.) Maintenance magnesium sulfate therapy has traditionally been continued for 24 hours after delivery. For eclampsia that develops postpartum, magnesium sulfate is administered for 24 hours after the onset of convulsions. A few investigators have truncated this therapy duration to 12 hours and found no seizures (Anjum, 2016; Ehrenberg, 2006; Kashanian, 2016). And more recently, Ludmir and colleagues (2017) described salutary outcomes when magnesium sulfate therapy was stopped after delivery. That said, these studies are small, and the abbreviated magnesium regimen needs further study before being routinely implemented.


Obstentrics_Williams

Obstentrics_Williams. Using United States Pharmacopeia (USP) standards, magnesium sulfate USP is MgS04·7H20, and it contains 8.12 mEq magnesium per 1 g. Parenterally administered magnesium is cleared almost totally by renal excretion, and magnesium intoxication is unusual when the glomerular iltration rate is normal or only slightly reduced. Adequate urine output usualy correlates with preserved glomerular iltration rates. That said, magnesium excretion is not urine Row dependent, and urinary volume per unit time does not, per se, predict renal unction. Thus, serum creatinine leves must be mesured to etect a decreased glomeruar iltration rate.


Obstentrics_Williams

Obstentrics_Williams. Eclamptic convulsions are almost always prevented or arrested by plasma magnesium levels maintained at 4 to 7 mEq/L, 4.8 to 8.4 mg/dL, or 2.0 to 3.5 mmollL. But, one review of magnesium pharmacokinetics showed that most regimens result in much lower serum magnesium levels (Okusanya, 2016). This was especially true if only 1 g/hr was infused (Yefet, 2017). Importantly, the obesity epidemic has afected these observations (Cunningham, 2016). Tudela and colleagues (2013) described our observations from Parkland Hospital with magnesium administration to obese women. More than 60 percent of women whose body mass index (BMI) exceeded 30 kg/mrand who were receiving the 2 g/hr dose had sub therapeutic levels at 4 hours. hus, obese women would require 3 gl hr to maintain efective plasma levels. That said, most currently do not recommend routine magnesium level measurements (American College of Obstetricians and Gynecologists, 2013; Royal College of Obstetricians and Gynaecologists, 2006).


Obstentrics_Williams

Obstentrics_Williams. Patellar reRexes disappear when the plasma magnesium level reaches 10 mEq/L-about 12 mgl dL-presumably because of a curariform action. This sign serves to warn of impending magnesium toxicity. When plasma levels rise above 10 mEq/L, breathing becomes weakened. At 12 mEq/L or higher levels, respiratory paralysis and respiratory arrest follow (Somjen, 1966). Treatment with cacium gluconate or cacium chloride, 1 g intravenousy, along with discontinuation of forther manesium suate, usualy reverses mid-to-moderate respiratory depression. One of these agents should be readily available whenever magnesium is being infused. Unfortunately, the efects of intravenously administered calcium may be short-lived if there is a steady-state toxic level. For severe respiratory depression and arrest, prompt tracheal intubation and mechanical ventilation are lifesaving. Direct toxic efects on the myocardium from high levels of magnesium are uncommon (McCubbin, 1981; Morisaki, 2000).


Obstentrics_Williams

Obstentrics_Williams. Because magnesium is cleared almost exclusivey by renal excre . tion, the dosages described wil become excessive if glomerular il tration is substantialy decreased. The initial 4-g loading dose of magnesium sulfate can be safely administered regardless of renal function. It is important to administer the standard load ing dose and not to reduce it under the mistaken conception that diminished renal function requires it. This is because after distribution, a loading dose achieves the desired therapeutic level, and the infusion maintains the steady-state level. Thus, ony the maintenance infusion rate should be altered with dimin ished glomerular iltration rate. Renal function is estimated by measuring plasma creatinine. Whenever plasma creatinine lev els arer> 1.0 mg/mL, serum magnesium levels are determined to guide the infusion rate.


Obstentrics_Williams

Obstentrics_Williams. After a 4-g intravenous dose administered over 15 minutes, mean arterial pressure falls slightly, accompanied by a 13-percent rise in cardiac index (Cotton, 1986b). Thus, magnesium lowers systemic vascular resistance and mean arterial pressure. At the same time, cardiac output is increased. These indings are coincidental with transient nausea and Rushing, and the cardiovascular efects persist for only 15 minutes despite continued magnesium infusion. Thurnau and associates (1987) showed that magnesium therapy led to a small but signiicant rise in the total magnesium concentration in the cerebrospinal Ruid. The magnitude of the elevation was directly proportional to the corresponding serum concentration.


Obstentrics_Williams

Obstentrics_Williams. Magnesium has anticonvulsant and neuroprotective efects in several animal models. Some proposed mechanisms of action include: (1) reduced presynaptic release of the neurotransmitter glutamate, (2) blockade of glutamatergic N-methyl-D-aspartate (NMDA) receptors, (3) potentiation of adenosine action, (4) improved calcium bufering by mitochondria, and (5) blockage of calcium entry via voltage-gated channels (Arango, 2008; Wang, 2012). In the uterus, relatively high serum magnesium concentrations depress myometrial contractility both in vivo and in vitro. With the suggested regimen, myometrial depression has not been observed, except for a transient decline in activity during and immediately ater the initial intravenous loading dose (Leveno, TABLE 40-12. Randomized Comparative Trials of Magnesium Sulfate Versus Phenytoin and Diazepam to Prevent Recurrent Eclamptic Convulsions


Obstentrics_Williams

Obstentrics_Williams. TABLE 40-12. Randomized Comparative Trials of Magnesium Sulfate Versus Phenytoin and Diazepam to Prevent Recurrent Eclamptic Convulsions Recurrent seizuresa 60/453 (1n3%) 126/452 (28%) 22/388 (5.6%) 66/389 (1n7%) Matenal deathsb 10/388 (2.6%) 20/387 (5.2%) 17/453 (3.8%) 24/452 (5.3%) aA11 comparisons p < 0.01n. blndividual comparisons nonsignificant, combined comparison p < .05. Data from Eclampsia Trial Collaborative Group, 1995. 1998; Szal, 1999; Witlin, 1997). Blood loss at delivery is not increased by standard magnesium treatment (Graham, 2016). However, inhibition of uterine contractility is magnesium dose dependent, and serum levels of at least 8 to 10 mEq/L are necessary to inhibit uterine contractions (Watt-Morse, 1995).


Obstentrics_Williams

Obstentrics_Williams. Magnesium administered parenterally promptly crosses the placenta to achieve equilibrium in fetal serum and less so in amnionic fluid (Hallak, 1993). Levels in amnionic luid rise with the duration of maternal infusion (Gortzak-Uzan, 2005). Magnesium sulfate has small but signiicant efects on the fetal heart rate pattern-specifically beat-to-beat variability (Hallak, 1999). Duy and associates (2012) reported a lower heart rate baseline that was within the normal range; decreased variability; and fewer prolonged decelerations. They noted no adverse outcomes.


Obstentrics_Williams

Obstentrics_Williams. Overall, maternal magnesium therapy appears safe for perinates (Drassinower, 2015). One MFMU Network study of more than 1500 exposed preterm neonates found no association between the need for neonatal resuscitation and cord blood magnesium levels Qohnson, 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. The study showed that neonatal depression occurs only if hypermagnesemia at delivery is severe.


Obstentrics_Williams

Obstentrics_Williams. Observational studies suggest a protective efect of magnesium against the development of cerebral palsy in very-Iowbirthweight newborns (Nelson, 1995; Schendel, 1996). At least ive randomized trials have also assessed neuroprotective efects in preterm neonates. These findings are discussed in detail in Chapter 42 (p. 824). Nguyen and colleagues (2013) expanded this possibility to include term newborn neuroprotection, but data were insuicient to draw conclusions. Last, in cases of preterm labor, magnesium has been given for several days for tocolysis (Chap. 42, p. 826). Administration in these instances has been associated with neonatal osteopenia (American College of Obstetricians and Gynecologists, 20 16c).


Obstentrics_Williams

Obstentrics_Williams. The multinational Eclampsia Trial Collaborative Group study (1995) involved 1687 women with eclampsia randomly allocated to one of three diferent anticonvulsant regimens: magnesium sulfate, diazepam, or phenytoin (Table 40-12). 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). Importantly, the aggregate maternal death rate of 3.2 percent with magnesium sulfate was signiicantly lower than that of 5.2 percent for the other two regimens.


Obstentrics_Williams

Obstentrics_Williams. In their review of more than 9500 treated women, Smith and coworkers (2013) reported the overall rate of absent patellar tendon reflexes to be 1.6 percent; respiratory depression, 1.3 percent; and calcium gluconate administration, 0.2 percent. Only one mother died due to magnesium toxicity. Our experiences are similar. In the more than 60 years of magnesium use at Parkland Hospital, only one woman has died from an overdose (P ri tchard, 1984). Dangerous hypertension can cause cerebrovascular hemorrhage and hypertensive encephalopathy, and it can trigger eclamptic convulsions in women with preeclampsia. Other complications include placental abruption and congestive heart failure induced by elevated hypertensive afterload.


Obstentrics_Williams

Obstentrics_Williams. Because of these serious sequelae, the working group for the National High Blood Pressure Education Program (NHBPEP) (2000) and the 2013 Task Force recommend treatment to lower systolic pressures to or below 160 mm Hg and diastolic pressures to or below llO mm Hg. Martin and associates (2005, 2016) reported provocative observations that highlight the importance of treating systolic hypertension. They described 28 selected women with severe preeclampsia who sufered an associated stroke. Most (93 percent) were hemorrhagic strokes, and all women had systolic pressures > 160 mm Hg before sufering their stroke. By contrast, only 20 percent of these same women had diastolic pressures > 110 mm Hg.


Obstentrics_Williams

Obstentrics_Williams. From other observations, it seems likely that at least half of serious hemorrhagic strokes associated with preeclampsia are in women with chronic hypertension (Cunningham, 2005). Long-standing hypertension results in development of CharcotBouchard aneuysms in the deep penetrating arteries of the lenticulostriate branch of the middle cerebral arteries. hese vessels supply the basal ganglia, putamen, thalamus, and adjacent deep white matter, as well as the pons and deep cerebellum. These unique aneurysmal weakenings predispose these small arteries to rupture during sudden hypertensive episodes.


Obstentrics_Williams

Obstentrics_Williams. Several drugs are available to rapidly lower dangerously elevated blood pressure in women with pregnancy-associated hypertension. he three most commonly employed are hydralazine, labetalol, and nifedipine. For years, parenteral hydralazine was the only one of these three available. But when parenteral labetalol was later introduced, it was proven to be equally efective for obstetrical use. Orally administered nifedipine has since also gained popularity. ll three of these are recommended as first-line agents by the American College of Obstetricians and Gynecologists (2017 a).


Obstentrics_Williams

Obstentrics_Williams. This is probably still the most commonly used antihypertensive agent in the United States for treatment of women with severe gestational hypertension. Hydralazine is administered intravenously with a 5-to 10-mg initial dose, and this is followed by 10-mg doses at 15-to 20-minute intervals until a satisfactory response is achieved. Although we will administer a third dose, the American College of Obstetricians and Gynecologists (2017 a) recommends labetalol therapy if severe hypertension persists after the second dose. Antepartum or intrapartum, the target response is a decline in systolic pressure to < 160 mm Hg and diastolic blood pressure to 90 to 110 mm Hg. Lower diastolic pressures risk compromised placental perfusion. Hydralazine has proven remarkably efective to prevent cerebral hemorrhage. Its onset of action can be as rapid as 10 minutes. Although repeated administration every 15 to 20 minutes may theoretically lead to undesirable hypotension, this has not been our experience


Obstentrics_Williams

Obstentrics_Williams. Its onset of action can be as rapid as 10 minutes. Although repeated administration every 15 to 20 minutes may theoretically lead to undesirable hypotension, this has not been our experience when given in these 5-to 10-mg increments.


Obstentrics_Williams

Obstentrics_Williams. At Parkland Hospital, between 5 and 10 percent of all women with intrapartum hypertensive disorders are given a parenteral antihypertensive agent. Antepartum, we usually give hydralaxine as described. We do not limit the total dose, and seldom is a second antihypertensive agent needed. We estimate that by severe superimposed preeclampsia, and hydralazine was injected more frequently than recommended. Her blood pressure in less than 1 hour dropped from 240-270/130-150 mm Hg to 1r10/80 mm Hg. Fetal heart rate decelerations characteristic of utero placental insuiciency became evident. Decelerations persisted until her blood pressure was increased with rapid crystalloid infusion. In some cases, this fetal response to diminished uterine perfusion may be confused with placental abruption and may result in unnecessary and potentially dangerous emergency cesarean delivery.


Obstentrics_Williams

Obstentrics_Williams. This efective intravenous antihypertensive agent is an Q-and nonselective 3-blocker. Some prefer its use over hydralazine because of fewer side efects. At Parkland Hospital, we give 10 mg intravenously initially. If the blood pressure has not decreased to the desirable level in 10 minutes, then 20 mg is given. The next 10-minute incremental dose is 40 mg and is followed by another 40 mg if needed. If a salutary response is not achieved, then an 80-mg dose is given. Sibai (2003) recommends 20 to 40 mg every 10 to 15 minutes as needed and a maximum dose of 220 mg per treatment cycle. The American College of Obstetricians and Gynecologists (2017a) recommends starting with a 20-mg intravenous bolus. If not efective within 10 minutes, this is followed by 40 mg, then 80 mg every 10 minutes. If hypertension persists, hydralazine is then given.


Obstentrics_Williams

Obstentrics_Williams. Comparative studies of hydralazine versus labetalol show equivalent results (Umans, 2015). In one trial, labetalol lowered blood pressure more rapidly, and associated tachycardia was minimal. But, hydralazine lowered mean arterial pressures to safe levels more efectively (Mabie, 1987). In another trial, maternal and neonatal outcomes were similar (Vigil-De Gracia, 2007). Hydralazine causes significantly more maternal tachycardia and palpitations, whereas labetalol more frequently leads to maternal hypotension and bradycardia. Both drugs have been associated with a reduced frequency of fetal heart rate accelerations (Cahill, 2013). Labetalol is not given to asthmatic women.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 40-20 Hydralazine was given at 5-minute intervals instead of 15-minute intervals. The there is a tendency to give a larger initial dose of hydralazine. But, this must be avoided. The response 100 not be predicted by hypertension severity. Thus, our protocol is to o 15 30 45 15 always administer 5 mg as the ini-Time (hours) tial dose. n adverse response to exceeding this initial dose is shown mean arterial pressure dropped from 180 to 90 mm Hg within 1 hour and was associated with in Figure 40-20. This woman had fetal bradycardia. Rapid crystalloid infusion raised the mean pressure to 115 mm Hg, and the fetus chronic hypertension complicated recovered.


Obstentrics_Williams

Obstentrics_Williams. his orally administered calcium-channel blocking agent has become popular because of its eicacy to control acute pregnancy-related hypertension. he American College of Obstetricians and Gynecologists (2017a), the NHBPEP Working Group (2000), and the Royal College of Obstetricians and Gynaecologists (2006) recommend a 10-mg initial immediate-release oral dose to be followed in 20 to 30 minutes with 10 to 20 mg if necessary. If not satisfactory, this is followed by labetalol. Nedipine given sublingualy is no longer recommended. his route is associated with dangerously rapid and extensive efects. Randomized trials that compared nifedipine with labetalol found neither drug definitively superior, but nifedipine lowered blood pressure more quickly (Scardo, 1999; Shekhar, 2016; Vermillion, 1999). Finally, nifedipine does not potentiate magnesium-related efects (Magee, 2015).


Obstentrics_Williams

Obstentrics_Williams. A few other generally available antihypertensive agents have been tested in clinical trials but are not widely used (Umans, 2015). These include verapamil, nitroglycerin, nitroprusside, ketanserin, nicardipine, and nimodipine (Belfort, 1990, 2003; Bolte, 2001; Cornette, 2016). There are also experimental antihypertensive drugs that may become useful for preeclampsia treatment (Lam, 2013). Potent loop diuretics can further compromise placental perfusion. Immediate efects include redistribution of the intravascular volume, which most oten is already reduced in severe preeclampsia (p. 718). herefore, before delivery, diuretics are not used to lower blood pressure (Zeeman, 2009; Zondervan, 1988). We use antepartum furosemide or similar drugs solely to treat pulmonary edema.


Obstentrics_Williams

Obstentrics_Williams. Lactated Ringer solution is administered routinely at a rate between 60 and 125 mL per hour, unless luid loss is unusual from vomiting, diarrhea, or diaphoresis, or, more likely, excessive blood loss with delivery. Oliguria is common with severe preeclampsia. hus, coupled with the knowledge that maternal blood volume is likely constricted compared with that of normal pregnancy, it is tempting to administer intravenous fluids more vigorously. But controlled, conservative luid administration is preferred for the typical woman with severe preeclampsia who already has excessive extracellular luid that is inappropriately distributed between intravascular and extravascular spaces. Infusion of large luid volumes enhances the maldistribution and thereby appreciably elevates the risk of pulmonary and cerebral edema (Dennis, 2012a; Sciscione, 2003; Zinaman, 1985). hus, for preeclamptic women with anuria, small incremental boluses can be given to maintain urine output above 30 mL per hour.


Obstentrics_Williams

Obstentrics_Williams. and cerebral edema (Dennis, 2012a; Sciscione, 2003; Zinaman, 1985). hus, for preeclamptic women with anuria, small incremental boluses can be given to maintain urine output above 30 mL per hour. Diminished intravascular volume from hemorrhage or luid loss from vomiting or fever can similarly be replaced by gradual incremental boluses. For labor analgesia with neuraxial analgesia, crystalloid solutions are infused slowly in graded amounts (Chap. 25, p. 496).


Obstentrics_Williams

Obstentrics_Williams. Women with severe preeclampsia who develop pulmonary edema most often do so postpartum (Cunningham, 1986, 2012; Zinaman, 1985). With suspected pulmonary edema in the eclamptic woman, aspiration of gastric contents, which may be the result of convulsions, anesthesia, or oversedation, should be excluded. here are three common causes of pulmonary edema in women with severe preeclampsia syndromepulmonary capillary permeability edema, cardiogenic edema, or a combination of the two.


Obstentrics_Williams

Obstentrics_Williams. Some women with severe preeclampsia-especially if given vigorous fluid replacement-will have mild pulmonary congestion secondary to permeability edema. his is caused by normal pregnancy changes magnified by the preeclamp�ia syndrome. Importantly, plasma oncotic pressure drops appreciably in normal term pregnancy because of decreased serum albumin concentration, and oncotic pressure falls even more with preeclampsia (Zinaman, 1985). Moreover, both increased extravascular luid oncotic pressure and increased capillary permeability are found in women with preeclampsia (Brown, 1989; 0ian, 1986).


Obstentrics_Williams

Obstentrics_Williams. Knowledge concerning cardiovascular and hemodynamic pathophysiological alterations associated with severe preeclampsia-eclampsia has accrued from studies done using invasive monitoring and a low-directed pulmonary artery catheter (see Fig. 40-5). Two conditions frequently cited as indications are preeclampsia associated with oliguria and that associated with pulmonary edema (Clark, 2010). Somewhat ironically, it is usually vigorous treatment of the former that results in most cases of the latter. The Task Force (2013) recommends against routine invasive monitoring. Such monitoring is best reserved for severely preeclamptic women with accompanying cardiac disease, renal disease, or both or with refractory hypertension, oliguria, and pulmonary edema.


Obstentrics_Williams

Obstentrics_Williams. Because the preeclampsia syndrome is associated with hemoconcentration, some have inused various fluids, starch polymers, albumin concentrates, or combinations thereof to expand blood volume (Ganzevoort, 2004). Older observational studies describe serious complications-especially pulmonary edema-with volume expansion (Benedetti, 1985; LOpez-Llera, 1982; Sibai, 1987b).


Obstentrics_Williams

Obstentrics_Williams. he Amsterdam randomized study reported by Ganzevoort and coworkers (2005a,b) was a well-designed investigation done to evaluate volume expansion. A total of216 women with severe preeclampsia were enrolled between 24 and 34 weeks' gestation. he study included women whose preeclampsia was complicated by HELLP syndrome, eclampsia, or fetal-growth restriction. In the group randomly assigned to volume expansion, each woman was given 250 mL of 6-percent hydroxyethyl starch infused over 4 hours twice daily. heir outcomes were compared with a control group, and none of these outcomes were significantly diferent (Table 40-13). Importantly, serious maternal morbidity and a substantive perinatal mortality rate accompanied their "expectant" management (see Table 40-9). Pulmonary edema 2.9 Placental abruption 3.8 l.0 Prolongation of pregnancy (mean) 11n.6 d 6.7 d EGA at death (mean) 26.7 wk 26.3 wk Prolongation of pregnancy (mean) 10.5 d 7.4 d EGA at delivery (mean) 31.6 wk 31.4 wk


Obstentrics_Williams

Obstentrics_Williams. Prolongation of pregnancy (mean) 11n.6 d 6.7 d EGA at death (mean) 26.7 wk 26.3 wk Prolongation of pregnancy (mean) 10.5 d 7.4 d EGA at delivery (mean) 31.6 wk 31.4 wk Neonatal death (%) 7.6 8.1 0.05. EGA = estimated gestational age; HELLP = hemolysis, elevated liver enzyme levels, low platelet count; RDS = respiratory distress syndrome. Data from Ganzevoort, 2005a, b. • Neuroprophylaxis-Prevention of Seizures aL studies, magnesium suate was reported to be superior to the Several randomized trials have tested the eicacy of seizure comparator agent to prevent eclampsia. Four of the larger studies prophylxis for women with gestational hypertension, with or are summarized in Table 40-14. In the study from Parland without proteinuria. In most of these, magnesium sulfate was Hospital, magnesium sulfate therapy was superior to phenycompared with another anticonvulsant or with a placebo. In toin to prevent eclamptic seizures in women with gestational


Obstentrics_Williams

Obstentrics_Williams. TABLE 40-14. Randomized Comparative Trials of Prophylaxis with Magnesium Sulfate and Placebo or Another Anticonvulsant in Women with Gestational Hypertension No. with Seizures/Total No. Treated (%) Gestational hypertensionb 0/1n049 (0) 10/1n089 (0.9) P < 0.001 Severe preeclampsia 1/345 (0.3) 1n1/340 (3.2) RR = 0.09 (0.1-0.69) Severe preeclampsia 40/5055 (0.8) 96/5055 (1n.9) RR = 0.42 (0.26-0.60) Severe preeclampsia 7/831 (0.8) 21/819 (2.6) RR = 0.33 (0.14-0.77) aAIl comparisons significant p < 0.05. blncluded women with and without proteinuria and those with all severities of preeclampsia. (Magpie Trial Collaboration Group, 2002. RR = relative risk.


Obstentrics_Williams

Obstentrics_Williams. blncluded women with and without proteinuria and those with all severities of preeclampsia. (Magpie Trial Collaboration Group, 2002. RR = relative risk. hypertension or preeclampsia (Lucas, 1995). In another, magnesium sulfate and nimodipine-a calcium-channel blocker with specific cerebral vasodilator activity-were compared in 1650 women with severe preeclampsia (Belfort, 2003). The rate of eclampsia was more than threefold higher for women allocated to the nimodipine group-2.6 versus 0.8 percent.


Obstentrics_Williams

Obstentrics_Williams. he largest comparative study was Manesium Suate or 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. In follow-up data of infants born to these mothers given magnesium sulfate, child behavior at approximately 18 months did not difer in those exposed compared with those not exposed to magnesium sulfate (Smyth, 2009). Who Should Be Given Magnesium Sulfate?


Obstentrics_Williams

Obstentrics_Williams. Who Should Be Given Magnesium Sulfate? Magnesium will prevent proportionately more seizures in women with correspondingly worse disease. However, severity is diicult to quantiy, and thus deciding which individual woman might benefit most from neuroprophylaxis is diicult. The 2013 Task Force recommends that women with either eclampsia or severe preeclampsia should be given magnesium sul ate prophylaxis. Again, criteria that establish "severity" are not totally uniform (see Table 40-2). At the same time, however, the 2013 Task Force suggests that women with "mild" preeclampsia do not need magnesium sulfate neuroprophylaxis. The conundrum is whether or not to give neuroprophylaxis to any of these women with "nonsevere" gestational hypertension or preeclampsia (Alexander, 2006).


Obstentrics_Williams

Obstentrics_Williams. In most other countries, and principally following dissemination of the Magpie Trial Collaboration Group (2002) study results, magnesium sulfate is now recommended for women with severe preeclampsia. In some, however, debate continues concerning whether therapy should be reserved for women who have an eclamptic seizure. We believe that eclamptic seizures are dangerous (pp. 722 and 745). Maternal mortality rates of up to 5 percent have been reported even in recent studies. Moreover, perinatal mortality rates are substantially increased (Abd EI Aal, 2012; Knight, 2007; Ndaboine, 2012; Schutte, 2008; von Dadelszen, 2012). Finally, the possibility of adverse longterm neuropsychological and vision-related sequelae of eclampsia have raised additional concerns that eclamptic seizures are not "benign."


Obstentrics_Williams

Obstentrics_Williams. Because of the foregoing, there is uncertainty about which women with nonsevere gestational hypertension should be given magnesium sulfate neuroprophylaxis. An opportunity to address these questions was aforded by a change in our prophylaxis protocol at Parkland Hospital. Before this time, the risk of eclampsia without magnesium prophylaxis was approximately 1 in 100 for women with mild preeclampsia (Lucas, 1995). Up until 2000, all women with gestational hypertension were given magnesium prophylaxis intramuscularly. Mter 2000, we instituted a standardized protocol for intravenously administered magnesium sulfate (Alexander, 2006). At the same time, we TABLE 40-15. Selective versus Universal Magnesium Sulfate Prophylaxis: Parkland Hospital Criteria to Define Severe Gestational In a woman with new-onset proteinuric hypertension, at least one of the following criteria is required: Systolic BP : 160 r diastolic BP : 110 mm Hg Proteinuria :2+ by dipstick in a catheterized urine


Obstentrics_Williams

Obstentrics_Williams. Systolic BP : 160 r diastolic BP : 110 mm Hg Proteinuria :2+ by dipstick in a catheterized urine Serum creatininen> 1n.1 mg/dL Platelet count < 1OO,OOO/1L above upper limit of normal range BP = blood pressure. Criteria based on those from [Jational High Blood Pressure Education Program Working Group, 2000; American (ollege of Obstetricians and Gynecologists, 2012; cited by Alexander, 2006. also changed our practice of universal seizure prophylaxis for all women with gestational hypertension to one of selective prophylaxis given only to women who met our criteria for severe gestational hypertension. These criteria, shown in Table 40-15, included women with :2+ proteinuria measured by dipstick in a catheterized urine specimen.


Obstentrics_Williams

Obstentrics_Williams. Following this protocol change, 60 percent of 6518 women with gestational hypertension during a 4Y2-year period were given magnesium sulfate neuroprophylaxis. The remaining 40 percent with nonsevere hypertension were not treated, and of these, 27 women developed eclamptic seizures-1 in 92. The seizure rate was only 1 in 358 for 3935 women with criteria for severe disease who were given magnesium sulfate, and thus these cases were treatment failures.


Obstentrics_Williams

Obstentrics_Williams. To assess morbidity, outcomes in 87 eclamptic women were compared with outcomes in all 6431 noneclamptic severely hypertensive women (Alexander, 2006). lthough most maternal outcomes were similar, almost a fourth of women with eclampsia who underwent emergent cesarean delivery required general anesthesia. his is a great concern because eclamptic women have laryngotracheal edema and are at a higher risk for failed intubation, gastric acid aspiration, and death. Neonatal outcomes were also a concern because the composite morbidity was increased tenfold in eclamptic compared with noneclamptic women-12 versus 1 percent, respectively. These outcomes included cord artery pH <7.0; 5-minute Apgar score <4; or unanticipated admission of a term newborn to an intensive care nursery.


Obstentrics_Williams

Obstentrics_Williams. Thus, if one uses the Parkland criteria for nonsevere gestational hypertension, approximately 1 of 100 such women who are not given magnesium sulfate prophylaxis can be expected to have an eclamptic seizure. A fourth of these women likely will require emergent cesarean delivery with attendant maternal and perinatal morbidity and mortality 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? he answer appears to be yes as suggested by the 20 13 Task Force. At Parkland Hospital, we only give magnesium neuroprophylxis to women with severe criteria.


Obstentrics_Williams

Obstentrics_Williams. During the past 20 years, the use of conduction analgesia for women with preeclampsia syndrome has proven ideal. Initial problems with this method included hypotension and diminished uterine perfusion caused by sympathetic blockade in preeclamptic women, with already attenuated hypervolemia. But pulmonary edema was mitigated by techniques that used slow induction of epidural analgesia with dilute solutions of anesthetic agents. his countered the need for rapid infusion of large volumes of crystalloid or colloid to correct maternal hypotension from neural blockade (Hogg, 1999; Wallace, 1995). These techniques are described in detail in Chapter 25 (p. 496). Importantly, epidural blockade avoids general anesthesia, in which the stimulation of tracheal intubation may cause sudden severe hypertension. Such blood pressure spikes, in turn, can cause pulmonary edema, cerebral edema, or intracranial hemorrhage. Finally, tracheal intubation may be particularly diicult and thus hazardous in


Obstentrics_Williams

Obstentrics_Williams. Such blood pressure spikes, in turn, can cause pulmonary edema, cerebral edema, or intracranial hemorrhage. Finally, tracheal intubation may be particularly diicult and thus hazardous in women with airway edema due to preeclampsia (American College of Obstetricians and Gynecologists, 20 17b).


Obstentrics_Williams

Obstentrics_Williams. At least three randomized studies have been performed to compare these methods of analgesia and anesthesia. Wallace and colleagues (1995) studied 80 women at Parkland Hospital with severe preeclampsia who were to undergo cesarean delivery. They had not been given labor epidural analgesia and were randomly assigned to receive general anesthesia, epidural analgesia, or combined spinal-epidural analgesia. heir average preoperative blood pressures approximated 170/110 mm Hg, and all had proteinuria. Maternal and perinatal outcomes in each group were similar. Maternal hypotension resulting from regional analgesia was managed with judicious intravenous fluid administration. In women undergoing general anesthesia, maternal blood pressure was managed to avoid severe hypertension. here were no serious maternal or fetal complications attributable to any of the three anesthetic methods. It was concluded that all three are acceptable for use in women with pregnancies complicated by severe


Obstentrics_Williams

Obstentrics_Williams. no serious maternal or fetal complications attributable to any of the three anesthetic methods. It was concluded that all three are acceptable for use in women with pregnancies complicated by severe preeclampsia if steps are taken to ensure a careful approach to the selected method.


Obstentrics_Williams

Obstentrics_Williams. Another randomized study included 70 women with severe preeclampsia receiving spinal analgesia versus general anesthesia for cesarean delivery (Dyer, 2003). Their maternal and fetal outcomes were equivalent. In a third study, 116 women with severe preeclampsia received either epidural or patient-controlled intravenous meperidine analgesia during labor (Head, 2002). More women-9 percent-from the group assigned to epidural analgesia required ephedrine for hypotension. As expected, pain relief was superior in the epidural group. Maternal and neonatal complications were similar between groups, and one woman in each group developed pulmonary edema. Importantly, epidural analgesia is not considered treatment of preeclampsia (Lucas, 2001; Ray, 2017).


Obstentrics_Williams

Obstentrics_Williams. Judicious fluid administration is essential in severely preeclamptic women who receive regional analgesia. Vigorous crystalloid infusion with epidural blockade in women with severe preeclampsia elevates pulmonary capillary wedge pressures (Newsome, 1986). Aggressive volume replacement in preeclamptic women raises their risk for pulmonary edema, especially in the first 72 hours postpartum (Clark, 1985; Cotton, 1986a). Finally, most cases of pharyngolaryngeal edema are related to aggressive volume therapy (Heller, 1983). Hemoconcentration or lack of norml pregnancy-induced hyper volemia is an almost predictable feature of severe preeclampsia eclampsia (see Fig. 40-7) (Zeeman, 2009). These women, who consequenty ack nomal pregnany hypervoemia, are much less toer ant of even normal blood oss than are nomotensive pregnant women.


Obstentrics_Williams

Obstentrics_Williams. Importantly, an appreciable fall in blood pressure soon ater delivery most oten 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 identiied, hemorrhage should be treated appropriately by crystalloid and blood transusion.


Obstentrics_Williams

Obstentrics_Williams. Although severe postpartum hypertension usually follows labor and delivery complicated by hypertension, 8 percent of women develop de novo hypertension postpartum (Goel, 2015). In either case, if diiculty arises in controlling severe hypertension or if intravenous hydralazine or labetalol are being used repeatedly, then oral regimens can be given. Examples include labetalol or another 3-blocker, or nifedipine or another calcium-channel blocker (Sharma, 2017). Women so treated are less likely to require readmission (Hirshberg, 2016). Persistent or refractory hypertension is likely aggravated by mobilization of pathological interstitial fluid and redistribution into the intravenous compartment, underlying chronic hypertension, or usually both (Sibai, 2012; Tan, 2002). Chronic, but not sporadic, administration of some nonsteroidal antiinflammatory drugs, namely ibuprofen, may aggravate postpartum hypertension in those with preeclampsia (Vigil-De Gracia, 2017; Viteri, 2017). In women with


Obstentrics_Williams

Obstentrics_Williams. administration of some nonsteroidal antiinflammatory drugs, namely ibuprofen, may aggravate postpartum hypertension in those with preeclampsia (Vigil-De Gracia, 2017; Viteri, 2017). In women with chronic hypertension and let-ventricular hypertrophy, severe postpartum hypertension can cause pulmonary edema from cardiac failure (Cunningham, 1986,2012; Sibai, 1987a).


Obstentrics_Williams

Obstentrics_Williams. Because persistence of severe hypertension corresponds to the onset and length of diuresis and extracellular fluid mobilization, it seems logical that furosemide-augmented diuresis might serve to hasten blood pressure control. One randomized trial included 264 postpartum preeclamptic women who, ater onset of spontaneous diuresis, were assigned to 20-mg oral furosemide given daily or to no therapy (Ascarelli, 2005). Women with mild disease had similar blood pressure control regardless of whether they received treatment or placebo. However, ater 2 days, women with severe preeclampsia who were treated, compared with those receiving placebo, had a lower mean systolic blood pressure-142 versus 153 mm Hg. They also less frequently required supplemental antihypertensive therapy during the remainder of hospitalization-14 versus 26 percent, respectively. In a recent randomized study, Veena and colleagues (2017) treated severe postpartum eclampsia with nifedipine plus furosemide or nifedipine


Obstentrics_Williams

Obstentrics_Williams. of hospitalization-14 versus 26 percent, respectively. In a recent randomized study, Veena and colleagues (2017) treated severe postpartum eclampsia with nifedipine plus furosemide or nifedipine alone. They reported that this prophylactic therapy signiicantly lowered the need for an additional antihypertensive-26 versus 8 percent, respectively.


Obstentrics_Williams

Obstentrics_Williams. We use a simple method to estimate excessive extracellular! interstitial luid. he posparum weight is compared with the most recentprenatal weight, either from the last clinic visit or on admission for delivery. Typically, soon ater delivery, maternal weight should be reduced by at least 10 to 15 pounds depending on newborn and placental weight, amnionic luid volume, and blood loss. Because of various interventions, especially intravenous crystalloid inusions given with labor epidural analgesia or during operative vaginal or cesarean delivery, women with severe preeclampsia oten have an immediate postpartum weight in excess of their st prenatal weight. If this weight increase is associated with severe persistent postpartum hypertension, then diuresis with intravenous urosemide is usually helpul in controlling blood pressure.


Obstentrics_Williams

Obstentrics_Williams. Occasionally, women have an atypical syndrome in which severe preeclampsia-eclampsia persists despite delivery. Martin and colleagues (1995) described 18 such women whom they encountered during a 10-year period. hey advocate single or multiple plasma exchange for these women. In some cases, 3 L of plasma was exchanged three times-a 36-to 45-donor unit exposure for each patient-before a response was forthcoming. Others have described plasma exchange performed in postpartum women with HELLP syndrome (Forster, 2002; Obeidat, 2002). In all of these cases, however, the distinction between HELLP syndrome and thrombotic thrombocytopenic purpura or hemolytic uremic syndrome was not clear (Tsai, 2016).


Obstentrics_Williams

Obstentrics_Williams. In our experiences with more than 50,000 women with gestational hypertension among nearly 450,000 pregnancies cared for at Parkland Hospital through 2017, we have encountered very few women with persistent postpartum hypertension, thrombocytopenia, and renal dysfunction who were diagnosed as having a thrombotic micro angiopathy (Dashe, 1998). hese latter syndromes complicating pregnancy were reviewed by Martin (2008) and George (2013) and their colleagues, who conclude that a rapid diagnostic test for ADAMTS-13 enzyme activity might be helpful to diferentiate most of these syndromes.


Obstentrics_Williams

Obstentrics_Williams. his is another cause of persistent hypertension, "thunderclap" headaches, seizures, and central nervous system indings. It is a form of postpartum angiopathy. Reversible cerebral vasoconstriction syndrome is characterized by difuse segmental constriction of cerebral arteries and may be associated with ischemic and hemorrhagic strokes. his syndrome has several inciting causes that include pregnancy, and particularly preeclampsia (Ducros, 2012). It is more common in women, and in some cases, vasoconstriction may be so severe as to cause cerebral ischemia and infarction. he appropriate management is not known at this time (Edlow, 2013).


Obstentrics_Williams

Obstentrics_Williams. Defective remodeling of the spiral arteries in some placentas is posited as a cause of at least one preeclampsia phenotype. Specifically, lack of deep placentation is linked with preeclampsia, placental abruption, fetal-growth restriction, and preterm birth (Wikstrom, 2011). With this type of "overlap syndrome," hypertensive disorders may serve as markers for subsequent preterm labor and fetal-growth restriction. For example, even in subsequent nonhypertensive pregnancies, women who had preterm preeclampsia are at higher risk for preterm birth and growth-restricted neonates (Bramham, 2011; Connealy, 2014; Palatnik, 2016).


Obstentrics_Williams

Obstentrics_Williams. In addition, women who have had either gestational hypertension or preeclampsia risk developing hypertension in future pregnancies (Lykke, 2009b). Generally, the earlier preeclampsia is diagnosed during the index pregnancy, the greater the likelihood of recurrence. And, the recurrence risk for preeclampsia is elevated further in women with the metabolic syndrome (Stekkinger, 2015). Sibai and colleagues (1986, 1991) found that nulliparas diagnosed with preeclampsia before 30 weeks had a recurrence risk as high as 40 percent during a subsequent pregnancy. In a prospective study of 500 women previously delivered for preeclampsia at 37 weeks, the recurrence rate in a subsequent gestation was 23 percent (Bramham, 2011).


Obstentrics_Williams

Obstentrics_Williams. As perhaps expected, women with HELLP syndrome have a substantive risk for recurrence in subsequent pregnancies. In two studies, the risk ranged from 5 to 26 percent, but the true recurrence risk likely lies beween these two extremes (Habli, 2009; Sibai, 1995). 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; Hnat, 2002).


Obstentrics_Williams

Obstentrics_Williams. Evidence has accrued that the preeclampsia syndrome is a marker for subsequent long-term cardiovascular and related morbidity and mortality (Table 40-16). hus, women with hypertension identified during pregnancy should be evaluated during the first several months postpartum. he working group of the NHBPEP (2000) concluded that hypertension attributable to pregnancy should resolve within 12 weeks of delivery. Hypertension persisting beyond this time is considered chronic (Chap. 50, p. 976). he Magpie Trial Follow-Up Collaborative Group (2007) reported that 20 percent of 3375 preeclamptic women seen at a median of 26 months postpartum had hypertension. Importantly, even if hypertension does not persist in the short term, convincing evidence suggests a higher risk for long-term cardiovascular morbidity.


Obstentrics_Williams

Obstentrics_Williams. Any hypertension during pregnancy is a risk marker for morbidity and mortality in later life (American College of Obstetricians and Gynecologists, 2013; Bellamy, 2007). In a case-control study from Iceland, Arnadottir and associates (2005) reported TABLE 40-16. Some Long-Term Consequences in Women with Preeclampsia Syndrome the prevalences of ischemic heart disease-24 versus 15 percent, and stroke-9.5 versus 6.5 percent, were significantly increased in women who had gestational hypertension compared with normotensive controls. In a Swedish population study of more than 400,000 women, those with recurrent preeclampsia have systolic dysfunction and a greater incidence of ischemic heart disease (Valensise, 2016). Diastolic dysfunction is also more common (Bokslag, 2017). Preeclampsia is also a risk for coronary artery calciication and idiopathic cardiomyopathy (Behrens, 2016; White, 2016).


Obstentrics_Williams

Obstentrics_Williams. Lyke and associates (2009a) cited indings from a Danish registry of more than 780,000 nulliparas. After a mean followup of almost 15 years, the incidence of chronic hypertension was fivefold higher in those who had gestational hypertension, 3.5-fold greater after mild preeclampsia, and sixfold higher after severe preeclampsia. After two hypertensive pregnancies, this incidence rose sixfold. Moreover, these women with pregnancy-associated hypertension are at increased risk for ype 2 diabetes (Rice, 2016). And, preeclampsia is a risk factor for later diabetic retinopathy and retinal detachment (Auger, 2017; Beharier,r2016). As emphasized by several investigators, other cofactors or comorbidities are related to acquisition of these long-term adverse outcomes (Gastrich, 2012; Harskamp, 2007; Hermes, 2012; Spaan, 2012b). These include the metabolic syndrome, diabetes, obesity, dyslipidemia, and atherosclerosis (Kajantie, 2017; Orabona, 2016; Stekkinger, 2015).


Obstentrics_Williams

Obstentrics_Williams. Individuals who are born pre term have greater ventricular mass later in life (Lewandowski, 20l3). And, women who have preeclampsia and who develop chronic hypertension later in life have an increased ventricular mass index before they become hypertensive (Ghossein-Doha, 2013). Finally, in at least some of these women, hypertensive cardiovascular pathologies appear to have begun near the time of their own births. A similar phenomenon is associated with preterm birth and with fetal-growth disorders.


Obstentrics_Williams

Obstentrics_Williams. Preeclampsia is also a marker for subsequent renal disease. lmost 15 percent of previously preeclamptic women have renal dysfunction (Lopes van Balen, 2017). In a 40-year study of Norwegian birth and end-stage renal disease linked registries, although the absolute risk of renal failure was small, preeclampsia was associated with a fourfold greater risk (Vikse, 2008). Women with recurrent preeclampsia had an even higher risk. These data need to be considered in light of the indings 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, Spaan and coworkers (2009) compared formerly preeclamptic women with a cohort of women who were normotensive at delivery. At 20 years following delivery, preeclamptic women were signiicantly more likely to be chronically hypertensive-55 versus 7 percent-compared with control women. They also had higher peripheral vascular and renovascular resistance and


Obstentrics_Williams

Obstentrics_Williams. women were signiicantly 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 low. These data do not permit conclusions as to cause versus efect.


Obstentrics_Williams

Obstentrics_Williams. Until recently, eclamptic seizures were believed to have no signiicant long-term sequelae. However, this may not be the case (heilen, 2016). Recall that almost all eclamptic women have multifocal areas of perivascular edema, and approximately a fourth also have areas of cerebral infarction (Zeeman, 2004a).


Obstentrics_Williams

Obstentrics_Williams. In several long-term follow-up studies in women with severe preeclampsia and eclampsia, brain white-matter lesions that followed eclamptic convulsions persist (Aukes, 2007, 2009, 2012). Speciically, when studied with MR imaging at a mean of 7 years, 40 percent of formerly eclamptic women had more numerous and larger aggregate white matter lesions compared with 17 percent of normotensive control women. These investigators later also observed these white-matter lesions in preeclamptic women without convulsions (Aukes, 2012). And, Siepmann and associates (2017) documented temporal lobe white matter changes and reduced cortical volume in previously preeclamptic women. In studies designed to assess clinical relevance, formerly eclamptic women had subjectively impaired cognitive functioning (Postma, 2014). Wiegman and associates (2012) reported that formerly eclamptic women at approximately 10 years had lower vision-related quality of life compared with control subjects. This likely


Obstentrics_Williams

Obstentrics_Williams. (Postma, 2014). Wiegman and associates (2012) reported that formerly eclamptic women at approximately 10 years had lower vision-related quality of life compared with control subjects. This likely coincides with an elevated risk for retinopathy described by Auger and colleagues (2017). Because no baseline studies were done before these women sufered from preeclampsia or eclampsia, the investigators appropriately concluded that a cause versus an efect of these white-matter lesions remains unknown.


Obstentrics_Williams

Obstentrics_Williams. Abalos E, Duley L, Steyn DW, et al: Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2:CD002252, 2014 Abbassi-Ghanavati M, Alexander ]M, McIntire DD: Neonatal efects of magnesium sulfate given to the mother. Am] Perinatol 29(10):795, 2012 Abd EI Aal DE, Shahin AY: Management of eclampsia at Assiut University Hospital, Egypt. Int] Gynaecol Obstet 116(3):232, 2012 Abdel-Hady ES, Fawzy M, EI-Negri M, et al: Is expectant management of early-onset severe preeclampsia worthwhile in low-resource settings? Arch Gynecol Obstet 282(1):23, 2010 Abdul-Karim R, Assali NS: Pressor response to angiotonin in pregnant and nonpregnant women. Am] Obstet Gynecol 82:246, 1961 Abenhaim HA, Bujold E, Benjamin A, et al: Evaluating the role of bedrest on the prevention of hypertensive disease of pregnancy and growth restriction. Hypertens Pregnancy 27(2):197,s2008 .


Obstentrics_Williams

Obstentrics_Williams. Abenhaim HA, Bujold E, Benjamin A, et al: Evaluating the role of bedrest on the prevention of hypertensive disease of pregnancy and growth restriction. Hypertens Pregnancy 27(2):197,s2008 . Abramovici D, Friedman SA, Mercer BM, et al: Neonatal outcome m severe preeclampsia at 24 to 36 weeks' gestation: does the HELLP (hemolysis, elevated liver enzyme, and low platelet count) syndrome matter? Am ] Obstet Gynecol 180:221, 1999 Airoldi ], Weinstein L: Clinical significance of proteinuria in pregnancy. Obstet Gynecol Surv 62: 11 ,2007 Ajne G, WolfK, Fyhrquist F, et al: Endothelin converting enzyme (ECE) aCtIvity in normal pregnancy and preeclampsia. Hypertens Pregnancy 22:215, 2003s Alanis MC, Robinson C], Hulsey TC, et al: Early-onset severe preeclampSia: induction of labor vs elective cesarean delivery and neonatal outcomes. Am ] Obstet Gynecol 199:262.e1, 2008


Obstentrics_Williams

Obstentrics_Williams. Alanis MC, Robinson C], Hulsey TC, et al: Early-onset severe preeclampSia: induction of labor vs elective cesarean delivery and neonatal outcomes. Am ] Obstet Gynecol 199:262.e1, 2008 Alexander ]M, Bloom SL, McIntire DD, et al: Severe preeclampsia and the very low-birthweight infant: is induction of labor harmful? Obstet Gynecol 93:485, 1999 Alexander ]M, Cunningham FG: Management. In Taylor RN, Roberts ]M, Cunningham FG (eds): Chesley's Hypertensive Disorders in Pregnancy, 4th ed. Amsrerdam, Academic Press, 2015 Alexander ]M, McIntire DD, Leveno K], et al: Magnesium sulfate for the prevention of eclampsia in women with mild hypertension. Am ] Obstet Gynecol 189:S89, 2003 Alexander ]M, McIntire DD, Leveno K], et al: Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women with gestational hypertension. Obstet Gynecol 108:826,2006


Obstentrics_Williams

Obstentrics_Williams. Alexander ]M, McIntire DD, Leveno K], et al: Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women with gestational hypertension. Obstet Gynecol 108:826,2006 Alexander ]M, Sarode R, McIntire DD, et al: Use of whole blood in the management of hypovolemia due to obstetric hemorrhage. Obstet Gynecol 113(6): 1320,s2009 AmbiaM, Yule CS, Wells E: Does fetal bradycardia during eclamptic seizure necessitate emergent cesarean delivety? Unpublished data, 2018 American College of Obstetricians and Gynecologists: Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 122: 1122, 2013 American College of Obstetricians and Gynecologists: Fetal growth restriction. Practice Bulletin No. 134, May 2013, Reairmed 2015 American College of Obstetricians and Gynecologists: Antepartum fetal surveillance. Practice Bulletin No. 145, ]uly 2014, Reairmed 2016a


Obstentrics_Williams

Obstentrics_Williams. Practice Bulletin No. 134, May 2013, Reairmed 2015 American College of Obstetricians and Gynecologists: Antepartum fetal surveillance. Practice Bulletin No. 145, ]uly 2014, Reairmed 2016a American College of Obstetricians and Gynecologists: Low-dose aspirin and prevention of preeclampsia: updated recommendations. Practice Advisory July 11, 2016b American College of Obstetricians and Gynecologists, Society �or Mat�r�alFetal Medicine: Magnesium sulfate use in obstetrics. Committee OpmlOn No. 652, January 2016c American College of Obstetricians and Gynecologists: Emergent therapy for acute onset, severe hypertension during pregnancy and the postpartum period. Committee Opinion No. 692, April 2017 a . . American College of Obstetricians and Gynecologists: Obstetric analgesia and anesthesia. Practice Bulletin No. 177, April 2017b


Obstentrics_Williams

Obstentrics_Williams. American College of Obstetricians and Gynecologists: Obstetric analgesia and anesthesia. Practice Bulletin No. 177, April 2017b Amorim MM, Santos LC, Faundes A: Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Am ] Obstet Gynecol 180:1283,s1999 Andersgaard AB, Herbst A, Johansen M, et al: Eclampsia in Scandinavia: incidence, substandard care, and potentially preventable cases. Acta Obstet Gynecol 85:929, 2006 Anjum S, Goel N, Shrama R, et al: Maternal outcomes after 12 hours and 24 hours of magnesium sulfate therapy for eclampsia. Int ] Gynaecol Obstet 132(1):68,s2016 Arango MF, Mejia-Mantilla ]H: Magnesium for acute traumatic brain injury.


Obstentrics_Williams

Obstentrics_Williams. Arango MF, Mejia-Mantilla ]H: Magnesium for acute traumatic brain injury. Cochrane Database Syst Rev 4:CD005400, 2008 rnadottir GA, Geirsson RT, Arngrimsson R, et al: Cardiovascular death in women who had hypertension in pregnancy: a case-control study. B]OG 112:286,2005 Ascarelli MH, Johnson V, McCreary H, et al: Postpartum preeclampsia management with furosemide: a randomized clinical trial. Obstet Gynecol 105:29,s2005 Askie LM, Henderson-Smart D], Stewart A: Antiplatelet agents for the prevention of preeclampsia: a meta-analysis of individual data. Lancet 369: 179, 2007 Auger N, Fraser WD, Paradis G, et al: Preeclampsia and long-term risk of maternal retinal disorders. Obstet Gynecol 129(1):42, 2017 Aukes AM, de Groot]c, Aarnoudse ]G, et al: Brain lesions several years after eclampsia. Am] Obstet Gynecol 200(5):504.el, 2009 AukesM, de Groot]C, Wiegman M], et al: Long-term cerebral imaging after pre-eclampsia. B]OG 119(9):1117,2012


Obstentrics_Williams

Obstentrics_Williams. Aukes AM,sWessei I, Dubois M, et al: Self-reported cogllltive functlonmg in formerly eclamptic women. Am] Obstet Gynecol 197(4):365.el, 2007 Bahado-Singh RO, Akolekar R, Mandai R, et al: First-trimester metabolomic detection of late-onset preeclampsia. Am ] Obstet Gynecol 208(1):58.e1, 2013 Bainbridge SA, Sidle EH, Smith GN: Direct placental efects of cigarette smoke protect women from pre-eclampsia: the specific roles of carbon monoxide and antioxidant systems in the placenta. Med Hypotheses 64: 17,s2005 Baltajian K, Bajracharya S, Salahuddin S, et al: Sequential plasma angiogenic factors levels in women with suspected preeclampsia. Am] Obstet Gynecol 215(I):89.e1,2016 Barakat R, Pelaez M, Cordero Y, et al: Exercise during pregnancy protects against hypertension and macrosomia: randomized clinical trial. Am ] Obstet GynecoIs214:649.e1, 2016 Barton CR, Barton ]R, O'Brien ]M, et al: Mild gestational hypertension: differences in ethnicity are associated with altered outcomes in women


Obstentrics_Williams

Obstentrics_Williams. clinical trial. Am ] Obstet GynecoIs214:649.e1, 2016 Barton CR, Barton ]R, O'Brien ]M, et al: Mild gestational hypertension: differences in ethnicity are associated with altered outcomes in women who undergo outpatient treatment. Am] Obstet Gynecol 186:896,2002


Obstentrics_Williams

Obstentrics_Williams. Barton ], Barton L, Istwan N, et al: Elective delivery at 34°17 to 366r weeks' gestation and its impact on neonatal outcomes in women with stable mild gestational hypertension. Am] Obstet Gynecol 204(1):44.e1, 2011 Bartsch E, Medcalf E, Park AL, et al: Clinical risk factors for preeclampSia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BM] 353:i 1753, 2016 Bdolah Y, Palomaki GE, Yaron Y, et al: Circulating angiogenic proteins in trisomy 13. Am] Obstet Gynecol 194(1):239,2006 Beharier 0, Davidson E, Sergienko R, et al: Preeclampsia and future risk for matenal ophthalmic complications. Am] Perinatol 33(7):703, 2016 Behrens I, Basit S, Lykke ]A, et al: Association between hypertensive disorders of pregnancy and later risk of cardiomyopathy.s]AMA 315(10)1026,s2016 Belfort M, Anthony], Saade G, et al: A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl] Med 348:304, 200�


Obstentrics_Williams

Obstentrics_Williams. Belfort MA, Anthonys], Buccimazza A, et al: HemodynamiC changes assocIated with intravenous infusion of the calcium antagonist verapamil in the treatment of severe gestational proteinuric hypertension. Obstet Gynecol 75:970, 1990 Belghiti], Kayem G, Tsatsaris V, et al: Benefits and risks of �xpectan� management of severe preeclampsia at less than 26 weeks gestation: the Impact of gestational age and severe fetal growth restriction. Am ] Obstet Gynecol 205(5):465.e1,s2011 Bellamy L, Casas ]P, Hingorani AD, et al: Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BM] 335:974, 2007 Benedetti T], Kates R, Williams V: Hemodynamic observations in severe preeclampsia complicated by pulmonary edema. Am ] Obstet Gynecol 152:330, 1985 Berg C], Harper MA, Atkinson SM, et al: Preventability of pregnancy-related deaths. Obstet Gynecol 106: 1228, 2005


Obstentrics_Williams

Obstentrics_Williams. Berg C], Harper MA, Atkinson SM, et al: Preventability of pregnancy-related deaths. Obstet Gynecol 106: 1228, 2005 Berks D, Steegers A, Molas M, et al: Resolution of hypertension and proteinuria after preeclampsia. Obstet Gynecol 114(6):1307,2009 Bloom SL, Leveno K]: Corticosteroid use in special circumstances: preterm ruptured membranes, hypertension, fetal growth restriction, multiple fetuses. Clin Obstet Gynecol 46: 150, 2003 Bokslag A, Franssen C, Teunissen PW, et al: Higher prevalence of diasto�ic dysfunction in women who have had a decade ago early onset preeclampSia. Abstract No. 66, Am] Obstet Gynecol 216:S47, 2017 Bolte AC, van Eyck], Gafar SF, et al: Ketanserin for the treatment of preeclampsia. ] Perinat Med 29: 14, 2001


Obstentrics_Williams

Obstentrics_Williams. Bolte AC, van Eyck], Gafar SF, et al: Ketanserin for the treatment of preeclampsia. ] Perinat Med 29: 14, 2001 Bombrys AE, Barton ]R, Habli 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] Perinatol 26:441, 2009 Bombtys E, Barton ]R, Nowacki EA, et al: Expectant management of severe preeclampsia at less than 27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management. Am] Obstet Gynecol 199:247.e1, 2008 Bramham K, Briley AL, Seed P, et al: Adverse maternal and perinatal outcomes in women with previous preeclampsia: a prospective study. Am ] Obstet GynecoIn204(6):512.e1,n2011 Brewer ], Owens MY, Wallace K, et al: Posterior reversible encephalopathy syndrome in 46 of 47 patients with eclampsia. Amn] Obstet Gynecol 208(6):468.e1,n2013


Obstentrics_Williams

Obstentrics_Williams. Brewer ], Owens MY, Wallace K, et al: Posterior reversible encephalopathy syndrome in 46 of 47 patients with eclampsia. Amn] Obstet Gynecol 208(6):468.e1,n2013 Broekhuijsen K, van Baaren G], van Pampus MG, et al: Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial. Lancet 385(9986):2492, 2015 Brookield F, Su F, Elkomy MH, et al: Pharmacokinetics and placental transfer of magnesium sulfate in pregnant women. Am J Obstet Gynecol 214:737.e1,n2016 Brosens I, Pijnenborg R, Vercruysse L, et al: The "Great Obstetrical Syndromes" are associated with disorders of deep placentation. Am ] Obstet GynecoI204(3):193,n2011 Brown CE, Purdy P, Cunningham FG: Head computed tomographic scans in women with eclampsia. Am] Obstet Gynecol 159(4):915, 1988


Obstentrics_Williams

Obstentrics_Williams. Brown CE, Purdy P, Cunningham FG: Head computed tomographic scans in women with eclampsia. Am] Obstet Gynecol 159(4):915, 1988 Brown A, Zammit VC, Lowe SA: Capillary permeabiliry and extracellular Auid volumes in pregnancy-induced hypertension. Clin Sci 77:599, 1989 Brownfoot Fe, Hastie R, Hannan N], et al: Metformin as a prevention and treatment for preeclampsia: efects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction. Am J Obstet Gynecol 214(3):356.e1, 2016 Budden A, Wilkinson L, Buksh M], et al: Pregnancy outcomes in women presenting with pre-eclampsia at less than 25 weeks gestation. Aust N Z ] Obstet GynaecoIn46(5):407, 2006 Bush KD, O'Brien JM, Barton JR: The utility of umbilical artery Doppler investigation in women with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol 184: 1087, 200n1


Obstentrics_Williams

Obstentrics_Williams. Buurma A], Turner R], Driessen ]H, et al: Genetic variants in pre-eclampsia: a meta-analysis. Hum Reprod Update 19(3):289,n2013 Cahill A, Odibo A, Roehl K, et al: Impact of intrapartum antihypertensives on electronic fetal heart rate (EFM) patterns in labor. Abstract No. 615, Am J Obstet Gynecoln208(1 Suppi):S262, 2013 Caritis 5, Sibai B, Hauth J, et al: Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl ] Med 338(1n1):70, 1998 Carty OM, Siwy J, Brennand JE, et al: Urinary proteomics for prediction of preeclampsia. Hypertension 57(3):561, 2011 Chaiworapongsa T, Robero R, Korzeniewski SJ, et al: Maternal plasma concentrations of angiogeniclantiangiogenic factors in the third trimester of pregnancy to identiy the patient at risk for stillbirth at or near term and severe late preeclampsia. Am J Obstet GynecoI208(4):287.e1, 2013


Obstentrics_Williams

Obstentrics_Williams. Chambers A, Cain W: Postpartum blindness: two cases. Ann Emerg Med 43:243, 2004 Chames MC, Livingston ]C, Ivester TS, et al: Late postpartum eclampsia: a preventable disease? Am] Obstet Gynecol 186: 1174, 2002 Chase L, McBride CA, Badger, et al: Association of pre-pregnancy and longitudinal change in angiotensin-II with preterm preeclampsia. Abstract No. 934, Am] Obstet Gynecol 216:5530, 2017 Chavarria ME, Lara-Gonzalez L, Gonzalez-Gleason A, et al: Prostacyclin/ thromboxane early changes in pregnancies that are complicated by preeclampsia. Am ] Obstet Gynecol 188:986, 2003 Chen BA, Parviainen K, Jeyabalan A: Correlation of catheterized and clean catch urine protein/creatinine ratios in preeclampsia evaluation. Obstet Gynecol 11n2:606,n2008 Chesley LC: Diagnosis of preeclampsia. Obstet Gynecol 65:423, 1985 Chesley LC (ed): Hypertensive Disorders in Pregnancy. Appleton-CenturyCrofts, New York, 1978


Obstentrics_Williams

Obstentrics_Williams. Chesley LC: Diagnosis of preeclampsia. Obstet Gynecol 65:423, 1985 Chesley LC (ed): Hypertensive Disorders in Pregnancy. Appleton-CenturyCrofts, New York, 1978 Chesley Le, Williams LO: Renal glomerular and tubular function in relation to the hyperuricemia of preeclampsia and eclampsia. Amn] Obstet Gynecol 50:367, 1945 Chowdhury ]R, Chaudhuri 5, Bhattacharyya N, et al: Comparison of intramuscular magnesium sulfate with low dose intravenous magnesium sulfate regimen for treatment of eclampsia.] Obstet Gynaecol Res 35:119,n2009 Christiansen M, Hedley PL, Placing 5, et al: Maternal serum resistin is reduced in irst trimester preeclampsia pregnancies and is a marker of clinical severity. Hypertens Pregnancy 34(4):422,n2015 Churchill 0, Beever GO, Meher S, et al: Diuretics for preventing preeclampsia. Cochrane Database Syst Rev 1 :CD004451, 2007 Cipolla MJ: Brief review: cerebrovascular function during pregnancy and eclampsia. Hypertension 50: 14, 2007


Obstentrics_Williams

Obstentrics_Williams. Cochrane Database Syst Rev 1 :CD004451, 2007 Cipolla MJ: Brief review: cerebrovascular function during pregnancy and eclampsia. Hypertension 50: 14, 2007 Cipolla MJ, Smith J, Kohlmeyer MM, et al:· SKCa and IKCa channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: efect of ischemia and reperfusion. Stroke 40(4): 1451,n2009 Cipolla M], Zeeman GG, Cunningham FG: Cerebrovascular (patho)physiology in preeclampsia/eclampsia. In Taylor RN, Roberts ]M, Cunningham FG (eds): Chesley's Hypertensive Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2015 Clark SL, Dildy GA III: Pulmonary artery catheterization. In Belfort M, Saade GR, Foley MR, et al (eds): Critical Care Obstetrics, 5th ed. West Sussex, Wiley-Blackwell, 2010 Clark SL, Cotton DB, Wesley L, et al: Central hemodynamic assessment of normal term pregnancy. m] Obstet Gynecol 161:1439, 1989


Obstentrics_Williams

Obstentrics_Williams. Clark SL, Cotton DB, Wesley L, et al: Central hemodynamic assessment of normal term pregnancy. m] Obstet Gynecol 161:1439, 1989 Clark SL, Divon MY, Phelan ]P: Preeclampsia/eclampsia: hemodynamic and neurologic correlations. Obstet Gynecol 66:337, 1985 Cleary KL, Roney K, Costantine M: Challenges of studying drugs in pregnancy for of-label indications: pravastatin for preeclampsia prevention. Semin PerinaroIn38:523,n2014 Cnossen ]5, de Ruyter-Hanhijavi H, van der Post JA, et al: Accuracy of serum uric acid determination in predicting pre-eclampsia: a systematic review. Acta Obstet Gynecol Scand 85(5):519, 2006 Coetzee EJ, Dommisse J, Anthony]: A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. B]OG 105(3):300, 1998


Obstentrics_Williams

Obstentrics_Williams. Coetzee EJ, Dommisse J, Anthony]: A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. B]OG 105(3):300, 1998 Conde-Agudelo A, Romero R, RobertS JM: Tests to predict preeclampsia. In Taylor RN, Roberts ]M, Cunningham FG (eds): Chesley's Hypertensive Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2015 Connealy B, Carreno e, Kase B, et al: A history of prior preeclampsia as a risk factor for preterm birth. Am J Perinatol 31(6):483, 2014 Conrad P, Stillman I, Lindheimer MD: he kidney in normal pregnancy and preeclampsia. In Taylor N, Roberts ]M, Cunningham FG (eds): Chesley's Hypenensive Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2015 Conelis T, Odutayo A, Keunenn], et al: he kidney in normal pregnancy and preeclampsia. Semin Nephrol 31(1):4, 2011


Obstentrics_Williams

Obstentrics_Williams. Conelis T, Odutayo A, Keunenn], et al: he kidney in normal pregnancy and preeclampsia. Semin Nephrol 31(1):4, 2011 Cornetten], Buijs EA, Duvekot J], et al: Hemodynamic efects of intravenous nicardipine in severely preeclamptic women with a hypertensive crisis. Ultrasound Obstet GynecoIn47(1):89, 2016 Costantine MM, Cleary K, Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Units Network: Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol 121(2 Pt 1):349,n2013 Costantine MM, Cleary K, Hebert MF, et al: Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. Am] Obstet Gynecol 214:720. e1,n2016


Obstentrics_Williams

Obstentrics_Williams. Cotton DB, Jones MM, Longmire 5, et al: Role of intravenous nitroglycerine in the treatment of severe pregnancy-induced hypertension complicated by pulmonary edema. Am J Obstet Gynecol 154:91, 1986a Cotton DB, Longmire 5, Jones MM, et al: Cardiovascular alterations in severe pregnancy-induced hypertension: efects of intravenous nitroglycerin coupled with blood volume expansion. Am J Obstet Gynecol 154: 1053, 1986b Creanga AA, Syverson C, Seed K, et al: Pregnancy-related mortaliry in the United States, 2006-2010. Obstet Gynecol 130(2):366,n2017 Crowther CA, Bouwmeester AM, Ashurst HM: Does admission to hospital for bed rest prevent disease progression or improve fetal outcome in pregnancy complicated by non-proteinuric hypertension? B]OG 99:13, 1992 Cunningham FG: Liver disease complicating pregnancy. Williams Obstetrics, 19th ed. (Suppl 1). Norwalk, Appleton & Lange, 1993 Cunningham FG: Peripartum cardiomyopathy: we've come a long way, but ...n. Obstet Gynecol 120(5):992, 2012


Obstentrics_Williams

Obstentrics_Williams. Cunningham FG: Peripartum cardiomyopathy: we've come a long way, but ...n. Obstet Gynecol 120(5):992, 2012 Cunningham FG: Severe preeclampsia and eclampsia: systolic hypertension is also important. Obstet Gynecol 105(2):237,n2005 Cunningham FG, Fenandez CO, Henandez C: Blindness associated with preeclampsia and eclampsia. Am] Obstet Gynecol 172: 1291, 1995 Cunningham FG, Lowe T, Guss 5, et al: Erythrocyte morphology in women with severe preeclampsia and eclampsia. Am ] Obstet Gynecol 153:358, 1985 Cunningham FG, Nelson DB: Disseminated intravascular coagulation syndromes in obstetrics. Obstet Gynecol 126(5):999,n2015 Cunningham FG, Nelson DB: Magnesium sulphate: too much of a good thing? B]OG 123:356,n2016 Cunningham FG, Pritchard JA, Hankins GO, et al: Peripartum heart failure: idiopathic cardiomyopathy or compounding cardiovascular events? Obstet :157, 1986 Cunningham FG, T wiclder 0: Cerebral edema complicating eclampsia. Am J Obstet Gynecol 182:94, 2000


Obstentrics_Williams

Obstentrics_Williams. Cunningham FG, T wiclder 0: Cerebral edema complicating eclampsia. Am J Obstet Gynecol 182:94, 2000 D'Anna R, Baviera G, Corrado F, et al: Plasma homocysteine in early and late pregnancy complicated with preeclampsia and isolated intrauterine growth restriction. Acta Obstet Gynecol Scand 83: 155, 2004 Dar P, Gebb J, Reimers L, et al: First-trimester 3-dimensional power Doppler of the uteroplacental circulation space: a potential screening method for preeclampsia. Am J Obstet Gynecol 203(3):238.e1, 2010 Dashe JS, Ramin SM, Cunningham FG: The long-term consequences of thrombotic microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy. Obstet GynecoIn91:662, 1998


Obstentrics_Williams

Obstentrics_Williams. Davidge S, de Groot C, Taylor N: Endothelial cell dysfunction and oxidative stress. In Taylor N, Roberts JM, Cunningham FG (eds): Chesley's Hypertensive Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2015 de Almeida Pimenta EJ, Silva de Paula CF, Duarte Bonini Campos JA, et al: hree-dimensional sonographic assessment of placental volume and vascularization in pregnancies complicated by hypertensive disorders. J Ultrasound Med 33(3):483, 2014 Demers S, Bujold E, Arenas E, et al: Prediction of recurrent preeclampsia using first-trimester uterine artery Doppler. Am J Perinatol 31 (2):99, 2014 Dennis AT, Castro J, Carr e, et al: Haemodynamics in women with untreated pre-eclampsia. Anaesthesia 67(10):1105, 2012a Dennis AT, Solnordal CB: Acute pulmonary oedema in pregnant women. Anaesthesia 67(6):646, 2012b


Obstentrics_Williams

Obstentrics_Williams. Dennis AT, Solnordal CB: Acute pulmonary oedema in pregnant women. Anaesthesia 67(6):646, 2012b De Paco e, Kametas N, Rencoret G, et al: Maternal cardiac output between 11 and 13 weeks of gestation in the prediction of preeclampsia and small for gestational age. Obstet Gynecol 111:292,n2008 De Snoo K: The prevention of eclampsia. Am J Obstet GynecoIn34:911, 1937 de Vries JI, van Pampus MG, Hague M: Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia: the FRUIT-RCT. J hromb Haemost 10(1):64, 2012


Obstentrics_Williams

Obstentrics_Williams. De Wolf F, De Wolf-Peeters e, Brosens I, et al: he human placental bed: electron microscopic study of trophoblastic invasion of spiral arteries. Am J Obstet Gynecoln137:58, 1980 DiFederico E, Genbacev 0, Fisher SJ: Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. m J PathoIn155:293, 1999 Drakeley AJ, Le Roux PA, Anthony J, et al: Acute renal failure complicating severe preeclampsia requiring admission to an obstetric intensive care unit. Am J Obstet Gynecol 186:253,n2002 Drassinower D, Friedman M, Levin H, et al: Does magnesium exposure afect neonatal resuscitation? Am J Obstet Gynecol 213:424.el, 2015 Duckworth S, Griin M, Seed PT, et al: Diagnostic biomarkers in women with suspected preeclampsia in a prospective multicenter study. Obstet Gynecol 128(2):245,n2016 Ducros A: Reversible cerebral vasoconstriction syndrome. Lancet Neurol 11(10):906,n2012 Duy CR, Odibo AO, Roehl A, et al: Efect of magnesium sulfate on fetal heart


Obstentrics_Williams

Obstentrics_Williams. Obstet Gynecol 128(2):245,n2016 Ducros A: Reversible cerebral vasoconstriction syndrome. Lancet Neurol 11(10):906,n2012 Duy CR, Odibo AO, Roehl A, et al: Efect of magnesium sulfate on fetal heart rate patterns in the second stage oflabor. Obstet GynecoIn119(6): 1129, 2012 Durr JA, Lindheimer MD: Control of volume and body tonicity. In Lindheimer MD, Roberts JM, Cunningham FG (eds): Chesley's Hypertensive Disorders in Pregnancy, 2nd ed. Stamford, Appleton & Lange, 1999 Dyer A,Els I, Farbas J, et al: Prospective, randomized trial comparing general with spinal anesthesia for cesarean delivery in preeclamptic patients with a nonreassuring fetal heart trace. Anesthesiology 99:561,n2003 Easterling TR, Benedetti TJ, Schmucker Be, et al: Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol 76:1061, 1990 Eclampsia Trial Collaborative Group: Which anticonvulsant for women with eclampsia? Evidence from the collaborative eclampsia trial. Lancet


Obstentrics_Williams

Obstentrics_Williams. a longitudinal study. Obstet Gynecol 76:1061, 1990 Eclampsia Trial Collaborative Group: Which anticonvulsant for women with eclampsia? Evidence from the collaborative eclampsia trial. Lancet 345:1455, 1995 Edlow JA, Caplan LR, O'Brien K, et al: Diagnosis of acute neurological emergencies in pregnant and post-partum women. Lancet Neurol 12(2): 175, 2013 Ehrenberg HM, Mercer BM: Abbreviated postpartum magnesium sulphate therapy for women with mild preeclampsia: a randomized controlled trial. Obstet Gynecol 108(4):833,n2006 Eichelberger Y, Baker Ml, Woodham PC, et al: Second-trimester maternal serum paraxanthine, CYP 1A2 activity, and the risk of severe preeclampsia. Obstet Gynecol 126(4):725,n2015 Erlebacher A: Immunology of the maternal-fetal interface. Annu Rev Immunol 31:387,n2013 Evans CS, Gooch L, Flotta 0, et al: Cardiovascular system during the postpartum state in women with a history of preeclampsia. Hypertension 58:57, 2011 Everett TR, Mahendru A, McEniery CM, et al: Raised


Obstentrics_Williams

Obstentrics_Williams. CS, Gooch L, Flotta 0, et al: Cardiovascular system during the postpartum state in women with a history of preeclampsia. Hypertension 58:57, 2011 Everett TR, Mahendru A, McEniery CM, et al: Raised uterine artery impedance is associated with increased maternal arterial stifness in the late second trimester. Placenta 33(7):572,n2012 Faas MM, Schuiling GA, Linton A, et al: Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia. Am J Obstet Gynecol 182:351,n2000


Obstentrics_Williams

Obstentrics_Williams. Facco FL, Parker CB, Reddy UM, et al: Association between sleep-disordered breathing and hypertensive disorders of pregnancy and gestational diabetes mellitus. Obstet GynecoIn129(1):31, 2017 Finnerty FA, Buchholz JH, Tuckman J: Evaluation of chlorothiazide (Diuril) in the toxemias of pregnancy. JAMA 166:141, 1958 Fisher S, Roberts JM: The placenta in normal pregnancy and preeclampsia. In Taylor RN, Roberts JM, Cunningham FG (eds): Chesley's Hypertensive Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2015 Fleischer A, Schulman H, Farmakides G, et al: Uterine artery Doppler velocimetry in pregnant women with hypertension. Am J Obstet Gynecol 154:806, 1986 Flowers CE, Grizzle JE, Easterling E, et al: Chlorothiazide as a prophylaxis against toxemia of pregnancy. A double-blind study. Am ] Obstet Gynecol 84:919, 1962


Obstentrics_Williams

Obstentrics_Williams. Flowers CE, Grizzle JE, Easterling E, et al: Chlorothiazide as a prophylaxis against toxemia of pregnancy. A double-blind study. Am ] Obstet Gynecol 84:919, 1962 Fonseca JE, Mendez F, Catano e, et al: Dexamethasone treatment does not improve the outcome of women with HELLP syndrome: a doubleblind, placebo-controlled, randomized clinical trial. Am J Obstet Gynecol 193:1591, 2005 Forster JG, Peltonen S, Kaaja R, et al: Plasma exchange in severe postpartum HELLP syndrome. Acta Anaesthesiol Scand 46:955,n2002 Fugate JE, Rabinstein A: Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 14(9):914, 2015 Gallo OM, Wright 0, Casanova e, et al: Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19-24 weeks' gestation. Am J Obstet GynecoI214:619.el, 2016


Obstentrics_Williams

Obstentrics_Williams. Gallo OM, Wright 0, Casanova e, et al: Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19-24 weeks' gestation. Am J Obstet GynecoI214:619.el, 2016 Gant NF, Chand S, Worley RJ, et al: A clinical test useful for predicting the development of acute hypertension in pregnancy. Am J Obstet Gynecol 120:1, 1974 Ganzevoort W, Rep A, Bonsel G], et al: A randomized trial of plasma volume expansion in hypertensive disorders of pregnancy: influence on the pulsatile indices of the fetal umbilical artery and middle cerebral artery. m J Obstet Gynecol 192:233, 2005a Ganzevoort W, Rep A, Bonsel GJ, et al: Plasma volume and blood pressure regulation in hypertensive pregnancy. J Hypertens 22: 1235, 2004 Ganzevoort W, Rep A, PERT A investigators, et al: A randomized controlled trial comparing two temporizing management strategies, one with and one without plasma volume expansion, for severe and early onset pre-eclampsia. BJOG 112:1337, 2005b


Obstentrics_Williams

Obstentrics_Williams. Gastrich MD, Gandhi SK, Pantazopoulos J, et al: Cardiovascular outcomes after preeclampsia or eclampsia complicated by myocardial infarction or stroke. Obstet GynecoIn120(4), 823, 2012 Gaugler-Senden IP, Huijssoon AG, Visser W, et al: Maternal and perinatal outcome of preeclampsia with an onset before 24 weeks' gestation. Audit in a tertiary referral center. Eur] Obstet Gynecol Reprod BioI 128:216, 2006 George IN, Charania RS: Evaluation of patients with microangiopathic hemolytic anemia and thrombocytopenia. Semin Thromb Hemost 39(2): 153, 2013 Gervasi MT, Chaiworapongsa T, Pacora P, et al: Phenotypic and metabolic characteristics of monocytes and granulocytes in preeclampsia. Am J Obstet Gynecol 185:792,n2001 Ghidini A, Locatelli A: Monitoring of fetal well-being: role of uterine artery Doppler. Semin Perinatol 32:258, 2008


Obstentrics_Williams

Obstentrics_Williams. Ghidini A, Locatelli A: Monitoring of fetal well-being: role of uterine artery Doppler. Semin Perinatol 32:258, 2008 Ghossein-Doha C, Peeters L, van Jeijster S, et al: Hypertension ater preeclampsia is preceded by changes in cardiac structures and function. Hypertension 62(2):382, 2013 Gillis EE, Mooney IN, Garrett MR, et al: Sildenafil treatment ameliorates the maternal syndrome of preeclampsia and rescues fetal growth in the Dahl salt-sensitive rat. Hypertension 67(3):647, 2016 Gilstrap Le, Cunningham FG, Whalley PJ: Management of pregnancyinduced hypertension in the nulliparous patient remote from term. Semin PerinatoIn2:73, 1978


Obstentrics_Williams

Obstentrics_Williams. Goel A, Maski MR, Bajracharya S, et al: Epidemiology and mechanisms of de novo and persistent hypertension in the postpartum period. Circulation 132(18):1726,n2015 Gortzak-Uzan L, Mezad 0, Smolin A: Increasing amniotic fluid magnesium concentrations with stable maternal serum levels. A prospective clinical trial. J Reprod Med 50:817, 2005 Graham NM, Gimovsky AC, Roman A, et al: Blood loss at cesarean delivery in women on magnesium sulfate for preeclampsia. J Matern Fetal Neonatal Med 29(11):1817,n2016 Groom K, McCowan L, MacKay L, et al: Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history: a randomized trial. Am J Obstet Gynecol 216(3):296.e1, 2017 Groom M, North A, Stone PR, et al: Patterns of change in uterine artery Doppler studies between 20 and 24 weeks of gestation and pregnancy outcomes. Obstet Gynecol 113(2):332, 2009


Obstentrics_Williams

Obstentrics_Williams. Guirguis GF, Aziz MM, Boccia Liang C, et al: Is preeclampsia an independent predictor of diastolic dysfunction: a retrospective cohort study. Pregnancy Hypertens 5(4):359, 2015 Habli M, Eftekhari N, Wiebracht E, et al: Long-term maternal and subsequent pregnancy outcomes 5 years after hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Am] Obstet GynecoI201(4):385.e1, 2009 Haddad B, Barton ]R, Livingston ]C, et al: Risk factors for adverse maternal outcomes among women with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am] Obstet Gynecol 183:444,n2000 Haddad B, Kayem G, Deis S, et al: Are perinatal and maternal outcomes dif ferent during expectant management of severe preeclampsia in the presence of intrauterine growth restriction? Am] Obstet Gynecol 196:237.e1, 2007


Obstentrics_Williams

Obstentrics_Williams. Haddad B, Winer N, Chitrit Y, et al: Enoxaparin and aspirin compared with aspirin alone to prevent placenta-mediated pregnancy complications. Obstet GynecoIn128(5):1053,n2016 Haggerty CL, Seifert ME, Tang G: Second trimester anti-angiogenic proteins and preeclampsia. Pregnancy Hypertens 2(2): 158, 2012 Hallak M, Berry SM, Madincea F, et al: Fetal serum and amniotic luid magnesium concentrations with maternal treatment. Obstet GynecoI81:185, 1993 Hallak M, Martinez-Poyer], Kruger ML, et al: he efect of magnesium sulfate on fetal heart rate parameters: a randomized, placebo-controlled trial. Am ] Obstet GynecoIn181:1122, 1999 Handor H, Daoudi R: Images in clinical medicine. Hypertensive retinopathy associated with preeclampsia. N Engl] Med 370(8):752,n2014