Gestational hypertension is the elevation of blood pressure during the second half of pregnancy or in the first 24 hours postpartum, without proteinuria and without symptoms. Treatment is generally not warranted since most patients will have only mild hypertension. Gestational hypertension at term in and of itself, has little effect on maternal or perinatal morbidity or mortality. However, approximately 40% to 50% of patients diagnosed with preterm mild gestational hypertension will develop preeclampsia (5). Parturients with severe gestational hypertension are at risk for adverse maternal and perinatal outcomes and management of these patients should be similar to those with severe preeclampsia (5). If a woman with gestational hypertension is considered to have a severe disease, she should receive antihypertensive therapy. Therefore, antihypertensive drugs should not be used during ambulatory management of these women (1,5,6).

Preeclampsia is defined as gestational hypertension plus proteinuria developing after 20 weeks of gestation. Preeclampsia can be mild or severe (Table 28-1). If a 24-hour urine collection is not possible, then proteinuria is defined as a concentration of at least 30 mg/dL (1+ on dipstick) on two occasions at least 4 hours apart.

Another severe form of preeclampsia is eclampsia, which is the occurrence of seizures not attributable to other causes.

The traditional criteria to confirm a diagnosis of preeclampsia are the presence of proteinuric hypertension (new onset of hypertension and new onset of proteinuria after 20 weeks of gestation). However, recent data suggest that in some women, preeclampsia and even eclampsia may develop in the absence of either hypertension or proteinuria (7). In many of these women, there are usually other manifestations of preeclampsia such as the presence of signs and symptoms or laboratory abnormalities. Criteria for atypical preeclampsia are described below:

In the absence of proteinuria, the syndrome of preeclampsia should be considered when gestational hypertension is present in association with persistent symptoms, or with abnormal laboratory tests. It is also important to note that 25% to 50% of women with mild gestational hypertension will progress to preeclampsia (5,7). The rate of progression depends on gestational age at onset of hypertension, that is, the rate approaches 50% when gestational hypertension develops before 32 weeks of gestation (4,5). In these women, the majority will result in preterm delivery and/or fetal growth restriction (5,7). Therefore, such women require close observation with frequent prenatal visits and serial evaluation of platelets and liver enzymes) and/or fetal growth (serial ultrasound).

A particularly severe form of preeclampsia is HELLP syndrome, which is an acronym for hemolysis (H), elevated liver enzymes (EL), and low platelet count (LP). The diagnosis may be deceptive because blood pressure may be only marginally elevated (8). A patient diagnosed with HELLP syndrome is automatically classified as having severe preeclampsia.

Hypertension is considered to be the hallmark for the diagnosis of preeclampsia; however, recent evidence suggests that in some patients with preeclampsia, the disease may manifest itself in the form of a capillary leak with proteinuria, ascites, pulmonary edema, generalized edema and excessive weight gain, or a spectrum of abnormal hemostasis with multiple organ dysfunction. Therefore, women with capillary leak syndrome with or without hypertension should be evaluated for platelet, liver enzyme, or renal abnormalities (7,9).

Hypertension complicating pregnancy is considered chronic if a patient is diagnosed with hypertension before pregnancy, if hypertension is present prior to 20 weeks of gestation, or if it persists longer than 6 weeks after delivery (10). Women with chronic hypertension are at risk of developing superimposed preeclampsia. Superimposed preeclampsia is defined as an exacerbation of hypertension and new onset of proteinuria (10).

Since the early 1980s, there have been several studies attempting to define the hemodynamic changes associated with severe preeclampsia. Almost all were prospective observational studies that used invasive hemodynamic monitoring with pulmonary artery (PA) catheters. These studies have provided valuable insight into the hemodynamic profiles in severe preeclampsia before and after the initiation of treatment with antihypertensives and fluids. Furthermore, the various etiologic factors and pathophysiologic changes contributing to the development of pulmonary edema in severe preeclampsia had been identified, thus facilitating the appropriate choice of treatment of this severe life-threatening complication.

In normotensive pregnant women, the limited data available from earlier studies show that cardiac output (CO), heart rate (HR), and stroke volume (SV) are significantly higher compared with nonpregnant values with no appreciable changes in central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) (34). Systemic and pulmonary vascular resistances (SVR and PVR) decrease (Table 28-3). In addition, plasma oncotic pressure (POP) drops
with narrowing of POP–PCWP gradients. Left ventricular function remains within normal limits with no evidence of hyperdynamic changes. These changes are outlined in detail in Chapter 1.

In patients with severe preeclampsia, the findings vary based on whether or not they had received any treatment with fluids or antihypertensives. Untreated preeclamptic patients almost always have the classic, uniform pattern consisting of low CVP, low PCWP, and CO, and a significantly elevated SVR indicating widespread vasoconstriction, decreased intravascular volume, and low filling pressures (35) (Table 28-4). Interestingly, pooled data from five different studies indicate that 86% of these untreated patients have the ventricular function curve shifted to the left indicating hyperdynamic left ventricular function (Fig. 28-3) (36).

Preeclamptic patients, who had received treatment with fluids and antihypertensive drugs, have no uniform hemodynamic pattern; they have either abnormally high or low values thus making the hemodynamic pathophysiology less clear. In most studies, CO, SV, HR, and PCWP are in the normal to high range with significantly elevated SVR (37,38,39) (Table 28-4). Furthermore, pooled data from various studies involving 89 treated preeclamptic patients show that 65 (73%) had hyperdynamic circulatory pattern, 18 patients (20%) had normal function, and 6 patients (7%) had depressed left ventricular function (Fig. 28-4) (36).

In untreated preeclamptic patients, there is a modest correlation between CVP and PCWP whereas in treated patients the situation is different. In patients receiving treatment, for any given CVP value, there is a wide variation in PCWP. This discrepancy had been well demonstrated by prior studies (40,41,42). The normal difference between PCWP and CVP is 4 and 5 mm Hg. In treated preeclamptic patients this value may vary widely between -1.6 and 17 mm Hg. In the majority of patients, PCWP–CVP differences tend to be significantly higher than normal limits (Table 28-5). A small increase in CVP may lead to a significant and disproportionate rise in PCWP and pulmonary edema. The etiology for this discrepancy and lack of correlation between CVP and wedge pressures is unclear, presumably related to factors such as slow equilibration of volume between the left and the right ventricles, “stiff” left ventricle with high left ventricular filling pressures (diastolic dysfunction), and the markedly elevated SVR (40,41,42).

Given the abovementioned hemodynamic changes, until a decade ago, invasive monitoring with PA catheters was considered crucial for the peripartum management of patients with severe preeclampsia. However, PA catheter placement is associated with significant risks including, life-threatening complications such as pneumothorax and pulmonary artery rupture. There is no evidence that invasive monitoring improves patient outcome in severe preeclampsia (43,44). Furthermore, most obstetric units lack the obstetric intensive care units (ICUs) and trained ICU nurses to monitor the patients. At present, the use of invasive techniques with PA catheters is recommended only for specific indications such as pulmonary edema, persistent oliguria, and massive hemorrhage (2).

More recently, noninvasive techniques such as echocardiography (ECHO) and Doppler ultrasound have gained popularity due to the accuracy and reliability and the excellent correlation with invasive techniques (45,46,47). Studies of central hemodynamics using ECHO mostly mirrors prior findings from invasive studies, and show a significant increase in SVR and other cardiac indices based on whether or not patients received treatments with fluids and antihypertensives. ECHO is particularly useful in the diagnosis and treatment of patients with pulmonary edema as discussed in the following section.

Pulmonary edema is one of the most serious complications of severe preeclampsia and is associated with high maternal and fetal morbidity and mortality. The incidence is 3% and the condition is largely preventable. Pulmonary edema in preeclampsia can be noncardiogenic or cardiogenic (45,47).

Noncardiogenic pulmonary edema is caused by increased capillary permeability due to the widespread endothelial damage of all vascular beds including the pulmonary vasculature. In addition, POP is significantly lower in preeclampsia with values of 17 mm Hg or less (compared to 18 to 21 mm Hg in healthy pregnant women), presumably due to hypoalbuminemia from hepatic dysfunction and ongoing renal loss. After delivery, POP can decrease to values as low as 13 mm Hg or less, possibly from iatrogenic fluid overload. This causes further narrowing of POP–PCWP difference leading to pulmonary edema. Noncardiac pulmonary edema is often self-limiting and responds well to standard treatment with no need for long-term interventions.

Cardiogenic pulmonary edema is caused by left ventricular systolic or diastolic dysfunction. In a landmark study, Mabie et al. (47) studied a group of 45 patients with pulmonary edema admitted to the obstetric ICU in our institution. The authors performed two-dimensional and M-Mode ECHO and continuous pulsed color Doppler ECHO in all patients. They identified three therapeutically and prognostically distinct groups: Those with systolic dysfunction; those with normal systolic function, but increased left ventricular mass and diastolic dysfunction; and the third group with normal hearts.

Those with systolic dysfunction, have severely depressed left ventricular contractile function. Such patients tend to be older, multiparous, and may have pre-existing cardiac diseases such as chronic hypertension and dilated cardiomyopathy. Pulmonary edema may occur in the antepartum or postpartum period. These patients should be admitted to the ICU and treatment with furosemide, digoxin, and oxygen should be initiated. Early and aggressive treatment is needed to stop the progression of the disease and worsening of the condition. The long-term prognosis in such patients is poor (47).

Patients with isolated diastolic dysfunction have a different hemodynamic profile. Typically, such patients have a normal left ventricular stroke volume and cardiac output. They have a significant left ventricular hypertrophy and normal SVR. The “stiffness” of the left ventricle results in high filling pressures, that is, even a small increase in filling volume, causes disproportionately large increases in left ventricular end-diastolic pressure and PCWP leading to pulmonary edema. These patients are usually obese and multiparous, with a history of chronic hypertension. They are overly sensitive to intravascular volume shifts. Treatment options include: Diuretics, antihypertensives, β-adrenergic blockers, and calcium channel antagonists. The long-term survival is better, compared to those with systolic dysfunction.

Not uncommonly, patients with pulmonary edema may have both systolic and diastolic dysfunction. Patients with normal hearts have noncardiogenic pulmonary edema as discussed earlier. Thus, patients with pulmonary edema pose a challenge and the accurate diagnosis of the different subtypes of cardiac dysfunction as well as the differentiation of cardiac and non cardiogenic pulmonary edema is difficult with routine clinical examination and chest x-rays (47). In such patients, it is imperative that the ECHO is performed to aid the management.

Generalized edema of preeclampsia involves the upper airway and a difficult tracheal intubation should be anticipated. Any incidental upper respiratory infection can also cause severe airway obstruction and shortness of breath in these patients.
Earlier studies showed that maternal oxygen dissociation curve is shifted to the left due to a decrease in 2,3-diphosphoglycerate level and increased carboxyhemoglobin derived from increased catabolism of red blood cells (Figs. 28-5 and 28-6) (48,49).

Central nervous system manifestations include severe headache, blurred vision, hyper-reflexia, and the most serious of all, eclamptic seizures (Fig. 28-7). Eclampsia is one of the major causes of maternal mortality, especially in the developing world. The exact etiology of eclampsia remains an enigma just as it is for preeclampsia. Available data suggest two opposing factors namely, the syndrome of hypertensive encephalopathy or alternatively, cerebral vasospasm causing areas of cerebral ischemia (50). In preeclampsia, the larger proximal cerebral blood vessels autoregulate blood flow in the distal smaller vessels. Episodes of high systemic blood pressures overwhelm the autoregulatory capacity causing hyperperfusion and forced overdistension of cerebral blood vessels. Failure of autoregulation results in vasogenic edema. Cerebral blood flow velocity is significantly elevated and shows a positive correlation with high systemic blood pressures (50). On the other hand, hypoperfusion and areas of ischemia from cerebral vasoconstriction can also contribute to the CNS symptoms. Other findings include a differential vascular sensitivity in the occipital lobes, especially in eclampsia leading to visual disturbances and even transient blindness.

Syndrome of posterior reversible encephalopathy (PRES) is worth mentioning because it is being recognized now as a syndrome, which involves headache, confusion, seizures, and visual disturbances, very similar to eclampsia but can occur in the absence of high blood pressures (51). Visual loss is the major finding. Retinal hemorrhages, disc edema, and macular exudates may be present. An MRI is crucial for the correct diagnosis. Correction of the etiologic factors is the only treatment for this condition (51).

Preeclampsia is associated with microvascular endothelial damage and enhanced clotting. The most common hematologic abnormality is thrombocytopenia. Platelet activation, increased platelet consumption, and decreased platelet lifespan are common features (Fig. 28-8). The incidence of thrombocytopenia with platelet counts <150,000 is 15% to 20%, and may be as high as 50% in severe cases. Platelets play a crucial role in the pathogenesis of preeclampsia by causing severe vascular endothelial damage with clumping and obstruction in the microvasculature (52,53). This results in areas of ischemia in vital organs such as liver, kidneys, heart, and brain. One earlier study suggested that thrombocytopenia may be due to increased platelet destruction caused by an autoimmune mechanism as evidenced by the increased platelet associated immunoglobulin concentrations which correlated inversely with the severity of thrombocytopenia (52,53). In a recent case-control study, Macey et al. compared activated platelets, platelet–monocyte/neutrophil aggregates, platelet microparticles, and four different markers of thrombin generation capacity in a group of patients with (n = 46) and without (n = 46) preeclampsia and nonpregnant controls (n = 42) (54). The authors found that all values were significantly elevated in preeclamptic patients compared with normotensive pregnant women. It is important to note that in normotensive pregnant women, although thrombin generation was increased, there was no evidence of platelet activation or formation of platelet leucocyte aggregates and microparticles, whereas in the preeclampsia group, significant platelet activation was present with further increase in thrombin generation capacity (54).

In addition to thrombocytopenia, preeclampsia adversely affects the platelet function. The presence of platelet dysfunction independent of the number platelets is a unique problem in preeclampsia. Platelet aggregometry studies, considered the gold standard for evaluating platelet function, have clearly demonstrated reduced platelet aggregation in preeclamptics compared with healthy pregnant women (55). However, aggregometry studies are time-consuming and not available at bedside. Other tests such as the template bleeding time, an in vivo platelet function test also showed prolongation despite the presence of adequate platelet counts (56) and is no longer used clinically.

Recently, the use of thromboelastography (TEG) (Hemoscope, Skokie, IL) and platelet function analyzer (PFA-100) has become popular. These tests are used to assess the platelet function in severe preeclampsia. The use of TEG parameters and platelet count in 52 healthy pregnant women, 140 patients with mild preeclampsia, and 114 patients with severe preeclampsia (57) showed that the incidence of thrombocytopenia with platelet count <1,000,000 mm³ was 3% in mild preeclamptic group and 30% in severely preeclamptic patients. The authors concluded that “severe preeclamptic women with platelet counts <100,000 mm³ are hypocoagulable, when compared to healthy pregnant women and other preeclamptic women” (57). TEG measures whole blood coagulation providing an assessment of all clotting factors including platelets but, not specific for platelet dysfunction, because the maximum amplitude (MA) values, one of the parameters of TEG is a composite of platelet activity and fibrinogen, and a relatively high fibrinogen level can compensate for the deficiencies in other clotting factors including platelets. Since the platelet dysfunction is the primary defect in preeclampsia, some authors question the use of TEG as the assessment tool for hemostasis before obstetric regional anesthesia (58). Yet there are some institutions that routinely use TEG prior to regional techniques in severe preeclamptic patients.

The platelet function analyzer (PFA-100) (Dade-Behring, Marburg, Germany) is a point-of-care device for platelet function assessment (59). The derived parameter closure time (CT) indicates platelet function. The PFA-100 device has been found to be as sensitive and specific as platelet aggregometry and is independent of fibrinogen levels. In a prospective observational study comparing hemostatic function in healthy pregnant women and preeclamptic patients using the PFA-100 and TEG devices, Davies and colleagues found that increasing severity of preeclampsia was associated with increasing prolongation of CT even in the presence of normal platelet counts. In the severe preeclampsia group, the CT was 155 ± 65 seconds, which far exceeded the 95% reference interval of the control group 70 to 139 seconds.
In contrast, TEG maximum amplitude (MA) values in the severe preeclampsia group 71 ± 8 mm remained within the 95% reference interval of 64 to 82 mm for MA values in the control group. In a post hoc analysis to determine the effect of low platelet count in lengthening CT, the data was analyzed after excluding patients with platelet counts less than 100,000 mm³. The mean CT was 105 ± 18 seconds in the control group (n = 92), while in mild preeclamptics (n = 22) the CT was 114 ± 22 seconds whereas it was significantly prolonged in the severe preeclampsia group (n = 22) with the CT value 135 ± 48 seconds (p < 0001) (59). The findings from this report unequivocally confirm, the presence of a primary hemostatic dysfunction in patients with severe preeclampsia, which is independent of the number of platelets. Other studies using the PFA-100 have shown similar findings (60,61).

Platelet count, liver enzymes, and serum creatinine are the required laboratory tests in patients with preeclampsia. Other coagulation tests are not needed in the presence of normal platelet count and liver enzymes or in the absence of placental abruption (62). Prolonged PT, aPTT, and decreased fibrinogen may be present in patients with platelet counts <100,000 mm³ (63) and therefore, these tests are recommended to evaluate hemostasis in such patients specifically, if regional anesthesia is planned. Thrombocytopenia persists after delivery and spontaneous resolution occurs within 67 ± 25 hours after delivery and 44 ± 17 hours after platelet nadir (64). In this study, the platelet counts were >100,000 mm³ by 111 hours after delivery and by 88 hours after platelet nadir in all patients in this study (64).

Hepatic damage in patients with severe preeclampsia is caused by vasospasm resulting in mid-zonal necrosis and multiple areas of infarctions. Subcapsular hemorrhages cause right upper quadrant pain (Fig. 28-9). Formation of a large subcapsular hematoma and rupture can sometimes occur in patients with HELLP syndrome. Lesions seen in liver biopsy and at autopsy show periportal hemorrhages, ischemic lesions, and fibrin depositions (Fig. 28-10). Elevated liver enzymes and serum bilirubin and decreased albumin levels are commonly present (8). Plasma pseudocholinesterase levels are found to be lower in severe preeclampsia although clinically, this does not seem to significantly affect the metabolism and duration of action of drugs such as succinylcholine (65).