Raymond O. Powrie
Part I: Hypertensive Disorders of Pregnancy
Hypertension during pregnancy has been classified by the American College of Obstetricians and Gynecologists into four distinct categories: (a) pre-eclampsia and eclampsia, (b) chronic hypertension (hypertension that was present before pregnancy), (c) chronic hypertension with superimposed pre-eclampsia or eclampsia, and (d) latent or transient hypertension of the third trimester (1). Most chronic hypertensive pregnant patients have essential hypertension, which has no appreciable effect during pregnancy unless end-organ damage is present. Chronic hypertension is seen in a critical care unit typically only when a patient has a hypertensive urgency/emergency unrelated to pregnancy, or if the patient has a secondary cause of hypertension that represents a short-term risk to maternal health. Similarly, latent or transient hypertension is also relatively benign, occurring in the last trimester or the immediate postpartum period, with a return of normotension by the first 3 weeks after delivery. It is pre-eclampsia and eclampsia (whether occurring de novo or superimposed upon pre-existing hypertension) that is most likely to require critical care support, and therefore will be the focus of this section.
Pre-eclampsia/Eclampsia
Pre-eclampsia is a multisystem disorder unique to human pregnancies. Its pathophysiology is not well understood, and its cause is unknown. It is associated with an increased risk of fetal loss, intrauterine growth restriction, and preterm birth, and remains a leading cause of maternal death worldwide. Eclampsia refers to pre-eclampsia that is complicated by seizures, but it is our present understanding that the underlying condition is the same (2).
Although much of the care of the pre-eclamptic patient will fall into the domain of the obstetrician, familiarity with the manifestations and management of pre-eclampsia is important for any critical care physician for two reasons. First, pre-eclampsia is far more common among women with medical problems such as chronic hypertension, thrombophilia, renal disease, diabetes, and collagen vascular disease, which are precisely the women that intensivists are most likely to care for during a pregnancy. Second, intensivists are often called to assist with the maternal medical manifestations of severe pre-eclampsia, and the help they provide will be greatly enhanced by an understanding of the underlying condition.
Risk Factors for Pre-eclampsia
Five percent of pregnancies are complicated by pre-eclampsia. It typically occurs in the final weeks prior to the due date, and is very rare prior to 20 weeks of gestation. The risk factors for pre-eclampsia are listed in Table 98.1. The diverse nature of the risk factors suggests that pre-eclampsia may be a common end point for a variety of processes related to placental dysfunction (3).
Etiology/Pathophysiology
Pre-eclampsia is believed to be an abnormal vascular response to the formation of the placenta. It is associated with endothelial cell dysfunction, activation of the coagulation system, enhanced platelet aggregation, and increased systemic vascular resistance. The maternal effects of these changes are manifest in the cardiovascular system, kidneys, lungs, and brain. Pathologic examination of affected maternal organs reveals areas of edema, endothelial swelling, microinfarctions, and microhemorrhages. The cardiovascular features of pre-eclampsia include decreased plasma volume (despite an increase in total body water and salt retention) and colloid osmotic pressure (largely due to a drop in serum albumin) (4,5). Generalized arteriolar vasospasm accounts for the hypertension in pre-eclampsia, which is often very labile.
The etiology of pre-eclampsia is one of medicine's greatest mysteries. Our present understanding suggests that the condition begins early in pregnancy and that there are three distinct, sequential phases that are necessary for its evolution (6,7). The first phase is incomplete invasion of the trophoblast into the endometrium, perhaps due to a maladaptive immune response in the mother, followed by inadequate “placentation” (formation of the placenta), which leads to the second phase in which decreases in the levels of angiogenic growth factors and increased placental debris are found in the maternal circulation. This stage of the development of pre-eclampsia is not associated with any clinical symptoms or signs. However, decreases in placental growth factor (PlGF) and elevations of fms-like tyrosine kinase 1 (sFlt) and endoglin can be detected (8,9,10). These changes incite a maternal inflammatory response. The third phase that leads to the maternal pre-eclamptic syndrome, as detected clinically, is the response of the maternal endothelium and cardiovascular system to these stressors, which is modulated by the woman's own level of metabolic and cardiovascular health. Although this response is manifested predominantly as hypertension and proteinuria, it is typically the less common cardiac, pulmonary, hematologic, neurologic, and hepatic effects of pre-eclampsia that present to intensivists. The importance of this model for the etiology of pre-eclampsia is the underlying concept that pre-eclampsia is evolving long before it becomes clinically apparent in the maternal syndrome.
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Table 98.1 Risk factors for pre-eclampsia |
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Clinical Features
Pre-eclampsia can manifest both as a fetal syndrome (abnormal fetal oxygenation, reduced amniotic fluid, and fetal growth restriction) and a maternal syndrome (proteinuria and hypertension with or without other multisystem abnormalities). In most patients, both the fetal and maternal syndrome will be apparent, but one or the other will often predominate in an individual case. This chapter will focus on the maternal manifestations.
Pre-eclampsia is defined by the maternal manifestations of hypertension and proteinuria occurring in the second half of pregnancy. The presentation and diagnostic features of this condition are reviewed in Tables 98.2A and 98.2B (11,12,13,14,15,16). Although hypertension >140/90 mm Hg and proteinuria >300 mg/24 hour are required for the diagnosis of pre-eclampsia, some cases may present initially without these features, or may present—as in the case of postpartum eclampsia—after some of these features have already resolved.
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Table 98.2A Clinical features of pre-eclampsia |
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Table 98.2B Laboratory features of pre-eclampsia |
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Severe pre-eclampsia is defined by one or more of the following: systolic blood pressure greater than 160 mm Hg; diastolic blood pressure greater than 110 mm Hg; mean arterial pressure greater than 120 mm Hg; proteinuria greater than 5 g/24 hours; oliguria less than 500 mL/24 hours; and headaches, visual disturbances, epigastric pain, pulmonary edema, or cyanosis. Eclampsia results when seizures occur that are not related to other underlying disorders. These features describe a group of patients with an increased risk of fetal and maternal morbidity for whom delivery should be strongly considered. Pre-eclamptic patients who lack any of the features of severe pre-eclampsia may have to be observed without moving toward delivery if the fetus is significantly premature and the mother remains under close observation; however, such patients are rarely seen in intensive care settings.
Life-threatening maternal complications of pre-eclampsia include severe hypertension, seizure, cerebral hemorrhage, pulmonary edema, disseminated intravascular coagulopathy (DIC), acute renal failure (ARF), and hepatic failure and/or rupture. Although these complications occur in the minority of cases of pre-eclampsia, they are reviewed here, as it is these complications that are most likely to require the care of a critical care physician.
Severe Hypertension
Although most clinicians would agree that the treatment goal for chronic hypertension in pregnancy is to keep the blood pressure below at least 160/100, the level at which elevated blood pressure should be treated in the setting of confirmed pre-eclampsia is controversial. All experts would agree that blood pressures greater than 180 mm Hg (systolic) and 110 mm Hg (diastolic) should be treated urgently, and that in the setting of obvious hypertensive end-organ damage (retinal hemorrhage, papilledema, pulmonary edema, severe headache, or renal failure), the blood pressure should be kept under 160/100 mm Hg. Beyond this consensus, opinions vary considerably.
Although no evidence suggests that treating blood pressures between 160/100 and 180/110 mm Hg in the setting of pre-eclampsia improves maternal or fetal outcomes, many experts believe that the risks for seizure, placental abruption, and cerebral hemorrhage are decreased by bringing blood pressures down into the normal or mildly hypertensive range. Other experts believe that because pre-eclampsia is a dynamic vasospastic disorder with associated target-organ ischemia, the safest approach is to let blood pressures run in a moderately severe range to avoid worsening ischemia in areas of regional vasospasm. This is a particularly important consideration if one believes that part of the reason for maternal hypertension in pre-eclampsia may be to improve placental perfusion. In the absence of direct evidence of end–target-organ damage from severe hypertension, it is our practice to treat all blood pressures over 160/105 mm Hg. However, although we treat these blood pressures urgently, we are careful to avoid any severe, sudden decreases in maternal blood pressure that may adversely affect uteroplacental and cerebral perfusion.
If urgent blood pressure reduction is required, intravenous labetalol or intravenous hydralazine can be used. Increasing evidence indicates that labetalol may be the better choice of the two; it is our preferred agent, although both agents are still acceptable (17). Hydralazine has been associated with an increased risk of an emergency cesarean in women who receive it while still pregnant and with lower Apgar scores in the infants of mothers who have been given this agent prior to delivery. Short-acting oral nifedipine is also used at some centers as an alternative to labetalol or hydralazine for the acute treatment of severe hypertension. Although its use in medical patients is now discouraged, its use for control of blood pressure in young pregnant or postpartum women without coronary artery disease remains an acceptable practice. Previous concerns about a drug interaction between magnesium and calcium channel blockers appear to be ill-founded (18). Diuretics should not be used in this setting unless pulmonary edema is present because, despite the edema that is so common in pre-eclamptic patients, most hemodynamic studies of pre-eclamptic women suggest that they are actually intravascularly volume depleted.
Once the patient has delivered, any antihypertensive agent can be used for blood pressure control. At that point, nitroprusside and nitroglycerin are excellent choices because of their very short half-lives.
Seizures
Seizures are the most well-known severe manifestation of pre-eclampsia. The risk of an eclamptic seizure in a patient with untreated pre-eclampsia is estimated to be about 1 in 200. Because of early identification of pre-eclampsia and the widespread use of magnesium prophylaxis, the incidence of eclampsia in the United States ranges from 1 in 1,000 to 1 in 20,000 deliveries. When it does occur, eclampsia is associated with a maternal mortality rate of 5% and a perinatal mortality rate between 13% and 30%.
Eclamptic seizures are typically of the grand mal variety, with clonic-tonic muscular activity followed by a postictal period. However, focal, jacksonian-type and absence seizures have been described. Most eclamptic seizures occur in the setting of established pre-eclampsia with hypertension and proteinuria. Classically, they are preceded by evidence of neuromuscular irritability such as tremulousness, agitation, nausea, vomiting, and/or clonus. However, some patients will present with seizure as their first manifestation of pre-eclampsia, usually occurring in the absence of hypertension or proteinuria.
The onset of eclamptic convulsions can be antepartum (38%–53%), intrapartum (18%–36%), or postpartum (11%–44%). Postpartum eclamptic seizures generally occur in the first 48 hours after delivery, but it is not unusual to see them occur anytime in the first week after delivery. Eclamptic seizures have been reported as late as 23 days postpartum.
The underlying pathophysiology of the eclamptic seizure is unclear. They cannot be attributed simply to severe hypertension, because eclampsia can be seen in patients with only mild elevations in blood pressure. Electroencephalograms may show epileptiform abnormalities, but usually show only a nonspecific diffuse slowing that may persist for weeks after delivery. Computed tomography (CT) and magnetic resonance imaging (MRI) of the eclamptic patient can be normal, or may show findings ranging from diffuse edema to focal areas of hemorrhage or infarction in the subcortical white matter and adjacent gray matter of the parieto-occipital lobes. The MRI is more sensitive in detecting abnormalities in eclamptic patients, but both CT and MRI of the brain can be normal, particularly if done in the first 24 hours after the seizure. When radiologic changes are present, some—but not all—of these changes usually resolve with time (19).
Management of eclamptic seizures
While moving toward delivery, a pre-eclamptic woman should receive an anticonvulsant to prevent eclamptic seizures. Magnesium sulfate is the drug of choice for this purpose (20). It halves the risk of eclampsia in patients with pre-eclampsia and lowers the risk of recurrent seizures and maternal death in women with eclampsia. It is superior to phenytoin and benzodiazepines in preventing further seizures. Magnesium is typically given as an intravenous bolus of 4 to 6 g, followed by a continuous intravenous infusion of 1 to 4 g/hour. Some clinicians will monitor plasma concentrations (which should run between 4 and 7 mmol/L), but others will simply administer the magnesium and monitor the patient for symptoms and signs of toxicity (hypotension, muscular weakness, and respiratory depression). Carefully monitoring for toxicity is important, particularly in patients with worsening renal function. Severe respiratory depression in a patient on magnesium should be treated with intravenous calcium. The only role of magnesium in pre-eclampsia is that of an anticonvulsant. Despite the possibility of a transient decrease in blood pressure with its initial administration, magnesium has no significant sustained effect on blood pressure. Its mechanism of action remains unclear, but it does not seem to have any intrinsic anticonvulsant effect, and may actually prevent seizures through its action as a cerebral vasodilator.
If the woman does have an acute eclamptic seizure, intravenous benzodiazepine is indicated to acutely stop the seizure, and magnesium should then be initiated if this has not already occurred. If an eclamptic convulsion occurs while a patient is receiving magnesium, most clinicians will add phenytoin to the regimen. Continued seizures should warrant the involvement of neurology and consideration of the use of phenobarbital or other hypnotic agents. Anticonvulsant therapy can generally be stopped once postpartum diuresis has begun and the manifestations of pre-eclampsia have started to improve.
Most patients with eclamptic seizures should have their head imaged with CT or MRI to rule out an intracerebral hemorrhage; the timing of these neuroimaging tests should be determined by the level of clinical suspicion for this diagnosis, and should not substantially delay delivery.
Cerebrovascular Accidents
Cerebrovascular accidents are three to seven times more common in pregnancy. Pre-eclampsia accounts for over a third of the strokes that do occur during pregnancy. At least half of the deaths from pre-eclampsia in the developed world are due to stroke. Most of the strokes in patients with pre-eclampsia will be related to intracerebral hemorrhage, but can also occur due to vasospastic ischemia (21). Pre-eclampsia-related stroke is often, but not always, associated with severe hypertension and/or eclamptic convulsions. Sudden onset or worsening of a headache, a change in mental status, or any focal neurologic complaint occurring in the context of pre-eclampsia should lead to consideration of this diagnosis and urgent neuroimaging.
Pulmonary Edema
Pulmonary edema occurs in about 3% of cases of pre-eclampsia, and can cause significant maternal morbidity (22,23). It occurs as a result of the interplay of pre-eclampsia-related pulmonary endothelial damage and the low plasma oncotic pressure seen in all pregnancies. Excessive intravenous fluid is also typically a contributing factor. It is often seen in the postpartum period after a patient has received a substantial amount of intravenous fluid in labor (or with cesarean delivery) and when mobilization of fluid from the involuting uterus begins. Pulmonary edema in this setting is often amenable to gentle diuresis but may be severe enough to warrant mechanical ventilation.
Echocardiographic studies demonstrate that transient systolic or diastolic ventricular dysfunction is present in up to one third of pre-eclampsia cases associated with pulmonary edema. This pre-eclampsia-related myocardial dysfunction is believed to be a manifestation of vasospastic coronary ischemia, and usually resolves rapidly with resolution of the pre-eclampsia. The author considers this to be a distinct entity from peripartum cardiomyopathy and does not believe there is a substantial recurrence risk of cardiac disease for these patients in a subsequent pregnancy.
Prevention and treatment of pulmonary edema
It is important to avoid excessive fluid administration to patients with pre-eclampsia because of their propensity for pulmonary edema. Ideally, one individual should be designated to approve and monitor all fluid administration in these patients. Regular auscultation of the lungs and use of transcutaneous pulse oximetry in patients with severe pre-eclampsia will help identify cases of pulmonary edema as they evolve. This careful observation should be continued in the postpartum period because pulmonary edema often occurs as late as 2 to 3 days after delivery. Acute treatment of pulmonary edema should involve supplemental oxygen, low-dose furosemide, and, if needed, morphine (23,24). Blood pressure control may help treat pulmonary edema by decreasing afterload. An echocardiogram should be obtained to look for an underlying cardiac contribution. Intubation and mechanical ventilation may become necessary if the above measures do not improve the patient's oxygenation.
Disseminated Intravascular Coagulation
Disseminated intravascular coagulation (DIC) can occur as a late and severe complication of pre-eclampsia or eclampsia (25). Because most patients with pre-eclampsia-related DIC have low platelet counts or elevated transaminase levels, DIC screening in the absence of these abnormalities is generally not necessary (26). However, a DIC screen should be ordered in all pre-eclamptic patients with rising liver enzymes, dropping platelet counts, and/or any abnormal bleeding. This is particularly important if there is a possibility of an operative delivery.
Acute Renal Failure
Pre-eclampsia is often associated with a mild degree of renal impairment manifesting as a slightly elevated creatinine or a decreased urine output. This is due to a combination of intravascular volume depletion, renovascular vasospasm, and a pre-eclampsia-related glomerular lesion known as glomerular endotheliosis. This mild renal impairment usually resolves rapidly after delivery.
Acute renal failure in pre-eclampsia is not common. If it does occur, acute tubular necrosis (ATN) and partial or total cortical necrosis are the most likely underlying lesions, and are thought to be caused by pre-eclampsia-related, vasospasm-induced renal ischemia. A history of transient hypotension is also typically present in these cases. The differential diagnosis includes ATN from sepsis or hemorrhage, an entity known as postpartum renal failure, or renal failure from causes unassociated with pregnancy such as hemolytic uremic syndrome, medication effects, or acute glomerulonephritis.
Most renal failure in the setting of pre-eclampsia is rapidly reversible, but if significant hypotension has occurred (as may happen with placental abruption or DIC-related hemorrhage), ATN or renal cortical necrosis may result and necessitate dialysis. In persons with sustained oliguria in the setting of pre-eclampsia, fluid challenges should be given cautiously because of the risk of pulmonary edema. Poor outcomes in pre-eclampsia are far more commonly related to pulmonary edema than they are to decreased urine output. Diuretics to improve urine output should be avoided in the absence of pulmonary edema because of the intravascular volume depletion present in most patients with pre-eclampsia.
If the patient is unresponsive to small fluid boluses, the use of central venous pressure monitoring may be a helpful, if not completely reliable, guide. The role of the pulmonary artery catheter in this context is unproven, and should only be used by nurses and physicians who are trained and experienced in its use. Increasing data from randomized control trials have shown that pulmonary artery catheters are of less benefit than previously believed in nonpregnant patients, and there is little reason to believe this tool has a uniquely beneficial role in the pregnant population.
Sustained oliguria in pre-eclampsia is unusual, and therefore significant and rapid peripartum renal deterioration should also lead to consideration of differential diagnoses that include the hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura, and an entity known as postpartum renal failure. It is therefore advisable to perform careful microscopic examination of urinary sediment and a peripheral smear in all pregnant or postpartum patients with oliguria (27).
HELLP Syndrome
A distinct clustering of the manifestations of pre-eclampsia is the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts). This constellation of findings represents a particularly severe form of pre-eclampsia with significant risk for maternal illness and fetal injury or death (28,29). HELLP occurs in up to 20% of cases of severe pre-eclampsia. The hemolysis is microangiopathic, and therefore schistocytes (fragmented erythrocytes) are seen on peripheral smears of the blood. Lactate dehydrogenase levels are usually increased. The liver enzymes may run into the hundreds. The thrombocytopenia can be precipitous and severe. High-dose dexamethasone is often given to treat patients with HELLP, but it is not clear that this intervention has clinically significant effects on outcomes, and the treatment remains supportive care coupled with delivery (30,31).
Hepatic Rupture or Hemorrhage
Epigastric or right upper quadrant pain and elevation of hepatic enzymes due to pre-eclampsia are common. When these factors are present, it suggests severe disease and pre-eclampsia-related hepatic edema and ischemia. It generally is associated with no more than a two- to fourfold increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT). When pain is severe and/or hepatic enzymes rise above this level, pre-eclampsia-related hepatic infarction, hemorrhage, and rupture should be considered and investigated with a hepatic ultrasound or CT (32). Acute fatty liver of pregnancy (AFLP) is also part of the differential diagnoses in these cases.
Diabetes Insipidus
Diabetes insipidus is a rare complication of pre-eclampsia with significant hepatic involvement. It can also be seen with acute fatty liver of pregnancy. It has been hypothesized that the acute liver dysfunction in these patients reduces the degradation of vasopressinase (an enzyme which itself degrades vasopressin), and results in a state of relative vasopressin deficiency (33). The course of the condition follows that of the underlying disorder and can be treated with additional vasopressin until it resolves.
The Role of Arterial Lines, Central Venous Pressure Monitors, and Pulmonary Artery Catheters in Pre-eclamptic Patients
Most severe pre-eclamptic patients have normal or hyperdynamic left ventricular function with normal pulmonary artery pressure. Thus, a central venous pressure (CVP) monitor usually is adequate to assess volume status and left ventricular function. However, severely pre-eclamptic patients may develop cardiac failure, progressive and marked oliguria, or pulmonary edema. In such cases, some authors suggest that a pulmonary artery (PA) catheter may be helpful for proper diagnosis and treatment, because right and left ventricular pressures may not correlate (34,35). Given that evidence has evolved that the routine use of pulmonary artery catheters may not be as beneficial in the care of nonobstetric patients as once believed, the rather limited literature about their use in obstetric populations cannot help but be questioned (36,37). No clear consensus exists as to their role in the management of pre-eclampsia (38). We rarely employ them in any obstetric patients, as the risks—especially on labor and delivery units where the personnel have less experience in their placement and interpretation—seem to outweigh the evidence justifying their use. When questions arise as to whether cardiac dysfunction is contributing to a pre-eclamptic patient's pulmonary edema and/or renal failure, we obtain an urgent bedside echocardiogram to guide our care and, in the absence of a significant cardiac cause, manage these patients clinically.
An intra-arterial catheter monitor may be indicated for protracted severe hypertension during therapy with potent antihypertensive agents or when there is a significant disparity between automated and manual cuff measurements of blood pressure.
Part II: Cardiac Disease
Cardiac disease during pregnancy has an incidence rate of 0.4% to 4%, and is associated with a maternal mortality of 0.4% to 6%, depending on the cardiac lesion being discussed (39). It, therefore, remains one of the leading causes of maternal mortality, and may actually be increasing as a cause of maternal mortality in the developed world. While rheumatic heart disease is far less of a concern in the West than it was several decades ago, it remains a problem, along with peripartum cardiomyopathy, pulmonary hypertension, adult congenital heart disease, and myocardial ischemia. These conditions will be the focus of this section. While many of the patients with cardiac disease who end up under the care of a critical care physician will have cardiac disease that was identified prior to pregnancy, a significant portion of patients will also have their cardiac disease present for the first time during pregnancy. The physiologic changes of pregnancy may exacerbate, and thereby unmask, previously undiagnosed cardiac disease, and pregnancy can predispose patients to the onset of certain cardiac diseases such as peripartum cardiomyopathy or ischemic heart disease. Some of the physiologic changes associated with pregnancy are reviewed below and are summarized in Table 98.3.
Physiologic Changes
1. Maternal blood volume gradually increases during pregnancy to 150% of nonpregnant levels (40). The increase in plasma volume (45%–55%) is greater than the increase in red blood cell volume (20%–30%), resulting in a relative anemia of pregnancy. This increase in blood volume is associated with an increase in cardiac output, which begins early in gestation and peaks at levels 30% to 40% over nonpregnant values between 20 and 30 weeks (40). The increase then plateaus until term.
2. The increase in cardiac output with gestation is dependent on heart rate and stroke volume. Heart rate gradually increases throughout pregnancy, starting as early as 4 weeks' gestation, with a 10% to 15% increase by term. Stroke volume, in contrast, peaks during the second trimester, with a 20% to 40% increase over the nonpregnant state.
3. During labor, cardiac output rises another 15% to 45% above prelabor values with an additional increase of 10% to 25% during uterine contractions. The increase in cardiac output in labor during contractions versus that seen between contractions is greater late in the first stage (34%) versus early in the first stage (16%) (41).
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Table 98.3 Hemodynamic changes in pregnancy |
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4. Oxygen consumption increases 20% during pregnancy, and may increase as much as 40% to 100% during active labor. In the immediate postpartum period, cardiac output increases 30% to 40% over the labor period or 60% to 80% over the nonpregnant state, with the increased blood volume shifting to the central circulation from the contracted uterus, as well as alleviation of aortocaval compression and a slight decrease in total peripheral resistance.
5. Cardiac output and other hemodynamic parameters are thought to return to their baseline prepregnant state by 6 weeks after delivery. However, cardiac output may remain elevated for up to 12 weeks (42).
6. Systemic arterial pressure decreases by 10 to 15 mm Hg over the first two trimesters and then gradually returns to baseline by term. Systemic vascular resistance decreases 10% to 20% during pregnancy. Moreover, systemic vascular resistance may remain decreased for at least 12 weeks post partum.
7. Venous pressure in the lower extremities increases and peaks near term as the gravid uterus compresses the inferior vena cava—especially when the patient is supine—while central venous pressure remains unchanged. Total body water increases by about 2 kg throughout pregnancy.
8. Invasive PA catheterization in low-risk, near-term pregnant patients (36–38 weeks) reveals a significant decrease in pulmonary vascular resistance, colloid oncotic pressure (COP), and COP–pulmonary artery occlusion pressure (PAOP) gradient, with no change in PAOP or left ventricular stroke work index (43).
9. With a significant increase in oxygen consumption, especially during labor, along with a decrease in functional residual capacity, the importance of adequate preoxygenation before rapid sequence induction of anesthesia cannot be overemphasized. Morbidity and mortality statistics from England and Wales reveal that anesthetic-related maternal mortality is predominantly caused by the inability to intubate the trachea or by pulmonary aspiration during general anesthesia (44). Thus, an awake orotracheal intubation should be considered when airway patency is suspect. The most experienced person available should typically be the individual who intubates pregnant women on a regular basis.
10. Despite an average 200- to 500-mL blood loss for routine, uncomplicated vaginal deliveries and an 800- to 1,000-mL blood loss for cesarean section deliveries, blood transfusions are seldom necessary because of the increased blood volume and the autotransfusion of approximately 500 mL of blood from the contracted uterus in the postpartum period. Although this increase in blood volume protects against blood loss at delivery, pulmonary congestion and cardiac failure can result in patients with underlying cardiac dysfunction.
11. Pregnant women have a predisposition to pulmonary edema. Physiologic changes in pregnancy that favor the development of pulmonary edema include an increase in intravascular volume, decreased blood viscosity (“physiologic anemia of pregnancy”), decreased COP, and fluid shifts, especially in the immediate postpartum period.
12. Patients with minimal cardiac reserve may tolerate early pregnancy, and subsequently decompensate from increasing blood volume and cardiac output in the late second trimester and early third trimester. Patients with moderate cardiac reserve may tolerate pregnancy well until labor and delivery or the puerperium. Thus, cardiac patients should continue to be closely monitored in the postpartum period because cardiac decompensation most frequently occurs during this time; the prepregnant baseline state may not be reached for as long as 12 weeks after delivery.
13. The enlarging uterus in the third trimester predisposes to aortocaval compression and decreased cardiac output in supine patients. Inferior vena cava compression occurs in up to 90% of near-term parturients in the supine position. However, only about 10% to 15% of patients manifest the supine hypotensive syndrome because of shunting of venous blood away from the caval system to the azygous system by the intervertebral plexus of veins. Patients most susceptible to supine hypotension are those with polyhydramnios and multiple gestation. However, in most patients in the lateral position, cardiac output is maintained. Turning from the supine to the lateral decubitus position increases cardiac output from 8% at 20 to 24 weeks to as much as 30% near term (45). Therefore, to avoid aortocaval compression, measures such as uterine displacement by maternal position (lateral decubitus), bed position (left lateral tilt), or uterine displacement devices are imperative, especially in the last trimester. Moreover, maternal hypotension and placental hypoperfusion from aortocaval compression can be compounded by regional anesthesia that interferes with compensatory sympathetic nervous system mechanisms (46).
14. As a consequence of these cardiovascular changes, normal symptoms of pregnancy can include fatigue, dyspnea, decreased exercise capacity, and light-headedness. Cardiac signs that may be seen in normal pregnancies include distended neck veins, peripheral edema, loud first heart sound, loud third heart sound, systolic ejection murmurs, and continuous murmurs (cervical venous hums and mammary souffle). Fourth heart sounds and diastolic murmurs occur rarely in normal pregnancy and should be considered pathologic unless proven otherwise. These changes are reviewed in Table 98.4. Therefore, the normal signs and symptoms of pregnancy may simulate pathologic disease states, thereby rendering the diagnosis of heart disease difficult.
15. Normal chest radiographic findings demonstrate increased lung markings (prominent pulmonary vasculature partly due to both increased blood volume and increased breast shadow). Electrocardiographic (ECG) changes may include a left QRS axis deviation and nonspecific ST-segment and T-wave changes.
Who is Most at Risk, and When is That Risk Greatest?
Table 98.5 classifies the risk of various cardiac lesions in pregnancy. When we speak about “risk” for these patients, we refer to congestive heart failure, arrhythmias, stroke, and death. Overall, about 13% of cardiac patients will suffer one of these outcomes in pregnancy. The presence of pulmonary hypertension is always associated with an increased risk, and this risk is commensurate to its degree of severity. Other factors associated with an increased risk of cardiac complications in pregnancy include the following (47):
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Table 98.4 Normal cardiac symptoms and signs in pregnancy |
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1. New York Heart Association (NYHA) functional class. This is perhaps the most important predictor of pregnancy outcome. Patients with NYHA class I and II cardiac disease generally have a good prognosis during pregnancy. Patients with NYHA class III and IV are more likely to experience complications and may require special management around the time of delivery.
2. Left-sided obstructive cardiac lesions. Patients with lesions such as aortic stenosis may have difficulty accommodating the increased blood volume and cardiac output seen in pregnancy, and become increasingly symptomatic. Interestingly, patients with regurgitant valvular lesions may have less difficulty in pregnancy, as cardiac output in these cases may benefit from the decrease in systemic vascular resistance seen in pregnancy.
3. Cyanosis
4. Left ventricular systolic dysfunction
5. Prior cardiac events or previous arrhythmia
Although pregnant women with cardiac disease may experience complications at any point during pregnancy, there are three periods of particular risk:
1. At the end of the second trimester when cardiac output has increased to its peak
2. At the time of labor and delivery when cardiac work may be increased dramatically by both pain and the autotransfusion of blood from the placenta and uterus with each contraction
3. In the first 72 hours following delivery when the uterine involution and resolution of pregnancy-related edema leads to mobilization of large amounts of fluid.
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Table 98.5 Peripartum risk of various cardiac lesions |
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General Management of Cardiac Patients During Pregnancy
Management of patients with cardiac disease in pregnancy in general should include good preconception counseling to assess and inform the patient of the risks associated with a pregnancy. Although no woman should be told that she “should never get pregnant,” a clear discussion of the risk is essential. With cases such as severe pulmonary hypertension or Eisenmenger syndrome, the patient should be strongly cautioned against pursuing a pregnancy. Women with congenital heart disease need also be informed that they are at increased risk of giving birth to a child with congenital heart disease.
If a woman with cardiac disease decides to pursue a pregnancy after a clear discussion of risk, the cardiologist should ensure that her cardiac status is clearly delineated and optimized. Ideally, any necessary investigations or interventions should be carried out prior to conception.
Once a woman is pregnant, regular visits with a medical specialist and an obstetrician trained in the care of high-risk pregnancies to watch for evidence of heart failure and arrhythmias are essential. Consultation with an obstetric anesthesiologist prior to delivery is also prudent.
As stated earlier, most cardiac medications can be used in pregnancy when indicated. Table 98.7 lists many common cardiac medications, and classifies them as to which drugs we know the most about regarding their safe use during pregnancy and which drugs we know the least. However, it should be emphasized that among the more commonly used cardiac medications, only angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and warfarin are known or strongly suspected to be human teratogens. Amiodarone has had mixed data with respect to its safety in pregnancy, with some reports of congenital hypothyroidism, goiter, prematurity, hypotonia, and bradycardia (48,49). While use in an acute setting is appropriate, it is not a first-line agent for maintenance therapy in pregnancy. Angiotensin-converting enzymes and angiotensin receptor blockers both have been associated with fetal anomalies, fetal loss, oligohydramnios, cranial ossification abnormalities, and neonatal renal failure. Although their use in the first trimester was once supported, recent evidence suggests they should not be used at any time in gestation (50). Warfarin is associated with a high risk of miscarriage and anomalies of the eyes, hands, neck, and central nervous system (51). Again, the guiding principle of managing critical illness in pregnancy should be that because fetal well-being is dependent upon maternal well-being, medications that are of benefit to maternal health should also be considered to be in the fetus' best interest. Useful references for reviewing the available safety data for medications during pregnancy and with breastfeeding are listed in Table 98.6.
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Table 98.6 Reviews of drug safety data for pregnancy and lactation |
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For any structural cardiac lesion, we typically will obtain an echocardiogram as a baseline early in pregnancy, in the third trimester, and with any change in clinical status. Additional investigations and interventions should be dictated by the patient's clinical status, and no needed test or procedure should be withheld during gestation. In particular, pregnancy should not limit necessary diagnostic testing (52). Ultrasound has a long history of safe use in pregnancy. The radiation exposure associated with plain film radiographs, nuclear medicine scans, angiography, and CT scans are all well below what is deemed acceptable during pregnancy. Contrast agents appear to be well tolerated by the fetus. Magnetic resonance imaging has not been associated with any ill effects in human pregnancies. Because fetal well-being is dependent on maternal well-being, more harm will generally be caused to a mother and her fetus by withholding necessary investigations than by obtaining them.
Women with congenital heart disease should undergo a detailed fetal ultrasound in the early second trimester to allow early diagnosis of congenital heart disease in the fetus. This will allow informed decision making by the mother, and will prepare the neonatology team should a problem be present.
Labor and delivery and the first 72 hours post partum warrant special consideration with respect to assembling the appropriate team and determining what monitoring will be needed. For most cardiac patients, a multidisciplinary patient care conference should be assembled well in advance of the anticipated time of delivery and a written care plan developed for the peripartum management of the patient. This team should generally include representation from critical care, nursing, anesthesia, obstetrics, and cardiology. The plans that are developed should be explicit and detailed and recognize that the labor and delivery room is a place where cardiac care is not commonly provided. Even the best-trained obstetricians and obstetric nurses will lack the volume of experience in the management of cardiac cases that is common among cardiac and critical care providers. It is our conviction that joint nursing of such patients by obstetric and cardiac-trained nurses during labor and delivery, followed by postpartum care in a cardiac or critical care unit, seems the ideal approach when possible. Table 98.8 offers a check list of parameters to be considered and addressed in a patient care conference dedicated to developing a delivery plan for a cardiac patient.
The mode of delivery should not generally be determined by medical concerns. The need for cesarean deliveries is generally dictated by obstetric concerns, and vaginal deliveries should generally be viewed as the safest and best option for cardiac patients. The choice between spontaneous labor and elective induction of labor should be made both on the likelihood of successful induction and the availability of medical expertise and resources should a cardiac patient go spontaneously into labor during the off hours and weekends.
Most patients should be kept in neutral fluid balance over the course of their delivery period, and careful monitoring of both input and output will be essential. Early and good anesthesia is important to decrease the cardiac work of delivery, and most patients should receive regional anesthesia in a manner that will minimize the need for the fluid boluses typically given to decrease the hypotension associated with establishing regional anesthesia. It is also important to consider that certain lesions, such as an aortic stenosis, may be highly volume dependent and require this additional fluid support.
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Table 98.7 Commonly used cardiac medications and their safety in pregnancy |
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Intra-arterial lines are advisable for cardiac lesions for which moment-to-moment monitoring of blood pressure might be desirable, such as severe aortic stenosis. The role of the pulmonary artery catheter in the laboring patient remains unclear and, in the absence of clear benefit, it is this author's opinion that their use during delivery should be limited to the most severe cardiac cases, if it is used at all.
Bacterial endocarditis prophylaxis is no longer recommended by the American Heart Association for vaginal or cesarean deliveries because the bacteremia associated with delivery is unlikely to cause endocarditis (53). If done at all, endocarditis prophylaxis should be reserved for patients with prosthetic heart valves, a prior history of subacute bacterial endocarditis, complex cyanotic congenital heart disease, or surgically constructed systemic pulmonary shunts or conduits, and an agent active against enterococci such as penicillin, ampicillin, or vancomycin should be utilized.
It is critical that all team members recognize that the cardiac patient remains at risk for at least 72 hours postpartum, so despite the sense of completion that comes with a successful delivery, caregivers need to remain vigilant for early signs of deterioration in the days following the birth.
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Table 98.8 Cardiac patient delivery plan check list |
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Specific Lesions
Mitral Stenosis
Rheumatic heart disease remains a common form of heart disease in pregnancy despite its declining incidence in the developed world. Mitral stenosis (MS) accounts for approximately 90% of the rheumatic valvular lesions in pregnancy. It often presents for the first time in pregnancy; risk factors include atrial fibrillation, pulmonary edema, and thromboembolic stroke. Most patients will experience some worsening of symptoms during pregnancy (54). Complication rates were found in one study to be 38% in moderately severe MS and 67% in severe cases (55). Avoidance of tachycardia, increased PA pressure, decreased systemic vascular resistance, and increased central blood volume are essential to patient management. For this reason, many patients will benefit from β-blockade to improve filling time during pregnancy (56). Echocardiograms in these patients should be done once every trimester and with any change in status in these patients. Careful attention should be paid to pulmonary pressures (although echocardiography may provide a less reliable estimate of pulmonary pressures in pregnancy). Pulmonary edema should be treated with diuretics and β-blockade. If symptoms persist despite optimal medical management, percutaneous mitral balloon valvuloplasty, commissurotomy, or even valve replacement may be warranted; all have been successfully performed in pregnancy (57,58,59). Open procedures may be associated with a higher risk of miscarriage, fetal loss, and preterm labor, and thus balloon valvuloplasty may be preferable at centers experienced with this procedure. Although surgery can be performed at any point in the pregnancy, the risk to the fetus is lowest in the second trimester.
If atrial fibrillation occurs, it should be treated promptly to decrease tachycardia and the associated risk of a low cardiac output state or degeneration into more malignant dysrhythmias. Rate control, full anticoagulation with heparin, and consideration of either medical or electrical cardioversion remain the core management principles in pregnant women with atrial fibrillation as they are for nonpregnant women.
For labor, vaginal delivery or cesarean, excellent pain control is important and is best achieved with early establishment of regional anesthesia. Control of pain will limit the undesirable effects of labor on heart rate and blood pressure. A conservatively dosed lumbar epidural anesthetic with special attention to fluid status, left uterine displacement, and careful use of α-adrenergic agents to treat hypotension is often helpful. These patients are dependent on high left ventricular filling pressures for their cardiac output (60,61). Obstetricians will generally try to limit the second stage of delivery (the “pushing” stage) and assist a prolonged second stage through the use of vacuum extractors or forceps to decrease maternal work. The role of pulmonary artery catheters and intra-arterial lines for cardiac patients in labor was discussed previously and remains unclear. If there is a group who benefits from these interventions, it will likely be those patients with severe obstructive lesions or very poor ejection fractions. If the pulmonary artery catheter is used for patients with mitral stenosis, it will be important to remember that the PAOP may overestimate left ventricular end-diastolic pressure.
Aortic Stenosis
Aortic stenosis is a valvular lesion rarely seen during pregnancy, and can be of rheumatic or congenital origin. Although bicuspid aortic valves are common, they are unlikely to be associated with significant stenosis in the childbearing years. They are, however, associated with an increased risk of both coarctation and dissection. While mild to moderate aortic stenosis is generally well tolerated in pregnancy, severe stenosis (defined as <1.0 cm2) carries a significant fetal and maternal risk. The rate of complication varies from 10% to 31% (62,63). Ideally, symptomatic aortic stenosis should be repaired prior to pregnancy. If the patient is classified as NYHA functional class III or IV while pregnant, consideration should be given to percutaneous valvuloplasty, surgical repair, or valve replacement. Ideally, such procedures are best done in the middle of the pregnancy but, if necessary, can be done at any time. When severe disease is identified after the first trimester, it is important to be aware that both labor and delivery and a late termination are associated with significant risks. Due to the fixed outflow obstruction, these patients will not tolerate sudden drops in volume or preload, and their peripartum period should be managed in such a way as to minimize the risk of such events and ensure the ability to respond rapidly if and when they do occur. Arterial lines are strongly advised, and the use of pulmonary artery catheters, while not proven, may be of benefit.
In the past, with severe stenotic lesions of the aorta, regional anesthesia has been avoided because of the resulting local anesthetic–induced sympathectomy, which can lead to bradycardia and decreased venous return. However, good results have been obtained in patients with severe aortic stenosis managed during labor with a carefully titrated epidural anesthetic (64,65).
Mitral and Aortic Insufficiency
Mitral insufficiency is the second most common valvular lesion seen in pregnancy, and is typically due to rheumatic heart disease (65). Aortic insufficiency is less common, and may be due to rheumatic, infectious, or rheumatologic conditions. These lesions, when found in isolation, tend to do well in pregnancy unless there is associated ventricular decompensation. Treatments when symptomatic may include diuretics, digoxin, or calcium channel blockers, but angiotensin receptor blockers should not be used despite the benefits of afterload reduction. Increases in systemic vascular resistance, decreased heart rate, atrial arrhythmias, and myocardial depressants may be poorly tolerated. Perhaps the most important peripartum issue for these patients is early regional anesthesia to prevent pain-associated increases in systemic vascular resistance.
Congenital Heart Disease
Approximately 25% of heart disease in pregnancy is congenital. It can be categorized as left-to-right shunt, right-to-left shunt, and aortic lesions.
Left-to-right Shunt
The most common congenital heart lesions are atrial septal defects (ASDs) and ventricular septal defects (VSDs), which are usually well tolerated in pregnancy. The risk of cardiac complications is greatest in patients with large defects. Congestive heart failure (due to increased blood volume in pregnancy leading to cardiac decompensation), atrial arrhythmias, shunt reversal (occurring due to sudden systemic hypotension), and thromboembolic disease are all possible complications seen with ASD and VSD in pregnancy. Ideally, hemodynamically significant septal defects should be repaired prior to pregnancy. However, when symptomatic septal defects present in pregnancy, the principles of management include (a) acetylsalicylic acid (ASA) 81 mg daily to prevent thromboembolism, (b) use of diuretics and digoxin to treat heart failure, (c) avoidance of hypotension with epidural administration or postpartum blood loss, and (d) rapid rate control with any arrhythmia.
Right-to-left Shunt and Pulmonary Hypertension
The high-risk congenital disorders in pregnancy include right-to-left shunts, as seen in Eisenmenger syndrome (any congenital heart lesion with a bidirectional or right-to-left shunt at the atrial, ventricular, or aortic level), and any other lesions associated with significant pulmonary hypertension. Patients with uncorrected cyanotic heart disease have increased spontaneous abortion rates, pulmonary embolization, congestive heart failure, and incidence for congenital heart defects in the fetus. A high hematocrit (≥65%) is not only an indication of the severity of the cardiac disease, but also in itself has a poorer prognosis secondary to complications from hyperviscosity (decreased cardiac output, organ hypoperfusion, and thrombosis).
During pregnancy, right-to-left shunting is increased because of decreased systemic vascular resistance, resulting in decreased pulmonary artery perfusion and hypoxia. A review on maternal and fetal outcome in patients with Eisenmenger syndrome reveals maternal mortality rates of 25% to 52% and fetal loss as high as 44% (66,67,68,69). Because of the grim prognosis for these pregnancies, these women should be strongly warned about the dangers of pursuing a pregnancy and, if they do become pregnant, should be offered the opportunity for an early termination. If they continue with the pregnancy, they may warrant hospitalization from 20 weeks onward. Oxygen should be administered for dyspnea, and prophylactic heparin should be considered throughout pregnancy and for 6 weeks postpartum. The mode of delivery should be determined on the basis of obstetric indications. Pulmonary artery catheterization can carry additional risks in patients with significant pulmonary hypertension, and should probably be avoided in these patients. Active efforts should be made to avoid sudden decreases in systemic vascular resistance, blood volume, and venous return. Increased pulmonary vascular resistance promotes right-to-left shunting; therefore, hypercapnia and hypoxia are to be avoided. How best to provide peripartum anesthesia to these patients is not clear, and discussion of this matter is beyond the scope of this chapter. What is clear is that if regional anesthesia is used, care must be taken to prevent precipitous drops in venous return. Patients with pulmonary hypertension and/or Eisenmenger syndrome should be observed for 72 hours postpartum in a cardiac setting, as many of the maternal deaths associated with these conditions will occur during this period.
Aortic Disease
Coarctation of the aorta and aortic manifestations of Marfan syndrome pose significant problems in pregnancy (70,71). The physiologic changes during pregnancy, including increased blood volume and increased blood pressure during labor and delivery, may promote aortic dissection in either of these conditions. Patients with coarctation of the aorta may also suffer from worsening hypertension or congestive heart failure in pregnancy.
Marfan syndrome is often associated with aortic dilation, aortic valve regurgitation, and mitral valve disease. Aortic dissection occurs in about 10% of patients with Marfan syndrome who undergo a pregnancy, and is most likely to occur if the aortic root measures beyond 4.5 cm in diameter (72,73). Ideally, women with this severity of aortic root dilation should have their aorta repaired prior to pregnancy. However, if they have not, serial echocardiography during pregnancy to watch for worsening dilation should be performed. If the root is increasing in size, aortic repair should be considered. The activity of patients with significant aortic dilation in pregnancy should be limited, and they should be placed on β-blockers to decrease shear stresses upon the vessel wall (74,75). Although we generally teach that the indications for cesarean delivery are obstetric and not medical, it is common practice to deliver women with aortic roots dilated beyond 4.0 cm by cesarean to avoid additional stressors on the aorta associated with the pain and pushing of a vaginal delivery. However, it is worth noting that the majority of aortic dissections in these patients occur prior to the onset of labor.
Aortic coarctation in pregnancy is associated with an increased risk of worsening hypertension and, less commonly, congestive heart failure or pre-eclampsia (76,77). It is much less likely to be associated with aortic dissection than Marfan syndrome, but dissection can and does occur. Blood pressure should be kept less than 160/100 mm Hg in these patients but not brought below 120/70 mm Hg, as there may be a significant gradient between blood pressure measurement in the arm and the estimated blood pressure of the placenta circulation that is distal to the aortic narrowing. β-Blockers are the preferred antihypertensives for these patients. Patients with coarctation can undergo a vaginal delivery but should have a limited second stage (i.e., prolonged pushing should be avoided by the use of vacuum extractor or forceps).
Tetralogy of Fallot
Tetralogy of Fallot is the most common cyanotic congenital heart disease. It consists of a ventricular septal defect, an overriding aorta, infundibular pulmonary stenosis, and secondary right ventricular hypertrophy. Patients with uncorrected tetralogy have significant complications in pregnancy including biventricular failure, arrhythmias, stroke, and risk of shunt reversal with worsening cyanosis. Preconception surgical repair should be undertaken if at all possible. If these patients do proceed with a pregnancy unrepaired, they should be managed in a manner similar to patients with Eisenmenger syndrome.
Patients with a surgically corrected tetralogy of Fallot who enter a pregnancy with a good functional status generally tolerate pregnancy well. The main risks are right-sided heart failure and arrhythmias. Their volume status should be watched throughout pregnancy and complaints of palpitations or syncope investigated with an event monitor. Delivery should include cardiac monitoring (78,79,80,81).
Other Repaired Congenital Heart Conditions
An increasing number of women with congenital heart problems that were repaired in childhood are reaching adulthood and undergoing pregnancy. In general, these patients' course in pregnancy is readily predictable by the parameters outlined earlier in this chapter. The majority will have a good pregnancy outcome for both themselves and their offspring if they enter the pregnancy with a good functional status.
Peripartum Cardiomyopathy
The National Heart, Lung, and Blood Institute (NHLBI) defines peripartum cardiomyopathy (PPCM) as the new onset of systolic dysfunction occurring in the absence of other plausible causes anytime between the final month of pregnancy up to 5 months postpartum. The incidence is between 1 in 3,000 and 1 in 15,000 pregnancies, and may be increasing (82,83). It is most commonly found in women who have twins, women who have pre-eclampsia/eclampsia, and older multiparous women. It is not clear if race is an independent risk factor for PPCM, but it is clear that African American women are more likely to die of PPCM than Caucasian women when it does occur. It is generally quoted that one third of these patients have complete resolution in the year following delivery, one third are left with residual cardiac dysfunction, and one third have progressive cardiac decompensation. The mortality rate is between 9% and 56%, and is highest in the subset of patients with persistent cardiomegaly beyond 6 months. Mortality can be due to end-stage heart failure, arrhythmia, or thromboembolism.
Pathologic findings include four-chamber enlargement with normal coronary arteries and valves. Light microscopic findings include myocardial hypertrophy and fibrosis with scattered mononuclear infiltrates. Clinical signs include symptoms of ventricular failure with possible associated arrhythmias and/or pulmonary emboli. Treatment includes bed rest, sodium restriction, diuresis, and preload/afterload reduction with a calcium channel blocker and hydralazine while pregnant and an angiotensin-converting enzyme inhibitor post partum. Patients with an ejection fraction less than 35% should be considered for anticoagulation with low-molecular-weight heparin while pregnant and warfarin post partum. Antidysrhythmics should be utilized in a manner similar to what would be done for any patient with an idiopathic cardiomyopathy. Although the exact risk remains unclear, there is evidence that peripartum cardiomyopathy may recur or worsen with subsequent pregnancies (84).
Hypertrophic Cardiomyopathy
During pregnancy, the course of hypertrophic cardiomyopathy (HCM) is variable because while the normal increase of blood volume is beneficial, the decrease in systemic vascular resistance and the increase in heart rate may be detrimental. Several large case series have highlighted the risks for these patients during pregnancy (85,86,87). Complications are not common but include congestive heart failure, chest pain, supraventricular tachycardias, ventricular tachycardia, and sudden death. Complications can occur at any point in the pregnancy or during labor as a result of stress, pain, and increased circulating catecholamines. Moreover, the immediate postpartum period can increase risk due to blood loss and decrease in systemic vascular resistance. Atrial fibrillation and supraventricular tachycardias are a common feature of this cardiac anomaly; thus, cardioselective β-blockers and verapamil are usually administered to these patients. Tocolytics, sympathomimetic agents, and digoxin should be avoided in these patients, as they may increase the risk of arrhythmia. The peripartum period should include cardiac monitoring and use of forceps or vacuum extractor so that the mother has to do little or no pushing. If regional anesthesia is employed, it should be done incrementally and with agents that minimize the risk of a sudden drop in preload.
Ischemic Heart Disease in Pregnancy
Although myocardial infarction in pregnancy is uncommon, with an incidence estimated at between 1 in 10,000 and 1 in 35,700, it does appear to be increasing. Risk factors include advancing age, pre-eclampsia, multiparity, chronic hypertension, and diabetes. Myocardial infarctions associated with pregnancy can occur at any time during gestation, with one report finding that 38% occurred antepartum, 21% intrapartum, and 41% in the first 6 weeks postpartum. Maternal mortality rate ranges from 7% to 35%, with a disproportionate number of deaths occurring among the antenatal cases (88,89,90). A large portion of pregnancy-associated myocardial infarctions are not due to atherosclerotic heart disease but instead due to coronary artery in situ thrombus formation, dissection, or spasm.
Diagnosis of ischemic heart disease in pregnancy does require considering it as part of the differential diagnosis, even in the absence of traditional risk factors. Clinicians should also be aware that creatine phosphokinase (CPK) and creatine kinase-MB (CK-MB) can be mildly elevated following a cesarean delivery and that troponin is a more specific marker of cardiac disease in the peripartum period. All forms of stress testing can be safely carried out in pregnancy, including nuclear imaging, although many centers prefer exercise echocardiography for this population. Diagnostic coronary angiography can and should be performed on pregnant women for the same indications as for nonpregnant patients.
Treatment of coronary artery disease remains largely unchanged in pregnancy. None of the medications commonly used to treat ischemic heart disease has been shown to cause adverse effects in the fetus. There is broad experience with low-dose aspirin, nitrates, β-blockers, and heparins in pregnancy. The paucity of data regarding the use of clopidogrel and the platelet glycoprotein IIb/IIIa inhibitors should limit their use in pregnancy to clinical scenarios with proven benefits. Coronary angiography, angioplasty and stenting, and thrombolysis have been and can be carried out safely throughout pregnancy (91,92,93,94).
The management of laboring patients with ischemic heart disease should be the same for other cardiac patients as discussed in the section above on general principles of management of cardiac disease at the time of delivery, and has strong parallels with the management of the cardiac patient undergoing general surgery.
Cardiac Arrhythmias in Pregnancy
Arrhythmias during gestation, and especially labor and delivery, appear to be more common than in the nonpregnant population (95). Hormonal changes, stress, and anxiety are contributing factors; however, most arrhythmias are not serious unless they are associated with organic heart disease.
Atrial Fibrillation
Atrial fibrillation occurring in pregnancy is usually associated with underlying disease such as mitral stenosis, peripartum cardiomyopathy, hypertensive heart disease, thyroid disease, or atrial septal defects. Patients with acute atrial fibrillation and significant hemodynamic changes require direct current cardioversion. Cardioversion appears to have no adverse effects on the fetus. Most patients, however, will require only medical management with rate-controlling or rhythm-restoring antidysrhythmics. β-Adrenergic blockers such as metoprolol, calcium channel blockers such as diltiazem or verapamil, and agents such as procainamide or digoxin can all be used safely during pregnancy. Amiodarone would not be considered a first-line agent for hemodynamically stable atrial fibrillation because of its possible effects on the fetal thyroid, but its use in pregnancy is not absolutely contraindicated. Anticoagulation for atrial fibrillation in pregnancy has the same indications as in nonpregnant patients, but the agent that must be used is heparin (usually in the form of subcutaneous low-molecular-weight heparin) because warfarin is associated with adverse fetal effects throughout gestation.
Supraventricular Tachycardia
Supraventricular tachycardias (SVTs) during pregnancy can occur with or without organic heart disease. Four percent of women with SVT report that their condition was first identified in pregnancy, and up to 22% state that pregnancy exacerbated their condition (96). In the absence of underlying cardiac disease, these tachycardias are not usually associated with increased morbidity. However, in patients with underlying structural cardiac disease or cardiomyopathy, SVT can lead to heart failure and death. Treatment protocols for supraventricular tachycardia remain unchanged in pregnancy and include carotid sinus massage, adenosine (97), calcium channel blockers, β-blockers, and direct current cardioversion (98,99).
Ventricular Arrhythmias
Ventricular arrhythmia during pregnancy may be associated with cocaine use, peripartum or any other form of cardiomyopathy, ischemic heart disease, and digitalis toxicity. Antiarrhythmic agents for which we have the most pregnancy data are lidocaine, β-blockers, and procainamide. Amiodarone is associated with an increased risk of fetal thyroid disease and, although its use in pregnancy is permissible, it should not be considered a first-line agent. Implantable defibrillators can and should be used when indicated in pregnancy, although they will need to be turned off during surgical procedures that require the use of cautery.
Bradycardia
Bradyarrhythmias during pregnancy are rare and may result from Lyme disease, hypothyroidism, myocarditis, and drug-induced, or congenital or acquired heart blocks. Permanent pacemakers are indicated for hemodynamically significant bradycardia. Patients with pre-existing pacemakers may need to have their baseline rate increased during pregnancy to mimic the normal physiologic changes of pregnancy.
Antiarrhythmic Drugs
Table 98.7 classifies the commonly used antiarrhythmic agents on the basis of what is known about their safety in pregnancy. Although there are obviously agents that we know more about than others, it is important to re-emphasize here that both mother and fetus benefit from the use of the best agent to control cardiac symptoms in pregnancy, and treatment should never be withheld from a pregnant woman based on theoretic fears of fetal harm.
Cardiac Surgery During Pregnancy
As in other semi-elective nonobstetric surgery during pregnancy, if nonurgent cardiac surgery is necessary, it should ideally take place during the second trimester. Deferring when possible until after the first trimester avoids the period of organogenesis and the risk of miscarriage. Third-trimester surgery carries the risk of precipitating preterm labor. However, surgery that is important to a patient's short-term well-being and survival should be done at any point in gestation as required. Coronary artery bypass grafts, valvuloplasties, valvular replacements, and aortic root replacements have all been done in pregnancy with good outcomes for mother and baby. When medical management can ameliorate the disease process, surgery may be postponed until the patient has recovered at least 4 to 6 weeks post partum; however, such decisions should be based on the best plan of action for the mother's safety rather than a cultural discomfort related to performing surgery in pregnancy.
Special intraoperative considerations in pregnant patients include (a) fetal monitoring during and after surgery, (b) maintenance of high flow and systemic mean arterial pressure (during cardiopulmonary bypass), and (c) uterine displacement devices if the patient is in the supine position for a median sternotomy. Although the pregnant patient has fared well with open heart procedures, fetal mortality rate can be high. Generally, better results are seen in closed heart procedures. Postoperatively, fetal monitoring should be continued and maternal analgesia maintained to avoid precipitating labor from accelerated postoperative pain.
Pregnancy after Prosthetic Valve Surgery
Patients with mechanical heart valve prostheses pose a significant risk during pregnancy as a result of their coagulation status. Fewer maternal and fetal complications occur with bioprosthetic valves but the need for reoperation on these valves for degenerative changes means they are not commonly used in women of reproductive age.
Heparin, typically low-molecular-weight heparin (LMWH), is the anticoagulant agent of choice during pregnancy because its molecular weight prevents placental crossover, and it is not teratogenic. It is now well established as the anticoagulant of choice in pregnancy for all indications except for mechanical heart valves. Questions still remain as to whether LMWH provides the same level of protection against mechanical valve thrombosis as warfarin. Although warfarin and its derivatives are associated with an increased risk of central nervous system anomalies and warfarin embryopathy, it may be that the risk is worth taking to prevent the catastrophic consequences of valve thrombosis (100,101,102). Some experts therefore recommend that women with mechanical heart valves use LMWH during the period of organogenesis, switch to warfarin for the majority of the pregnancy, and then switch back to LMWH close to term to avoid both fetal and maternal bleeding associated with delivery. Other experts would use LMWH but carry out frequent testing of the peak and trough heparin levels (also known as anti-Xa levels) to ensure that the patient is adequately anticoagulated.
Cardiac Transplant Patients
With the increasing number and survival of heart transplant recipients, increasing numbers of women who have undergone this procedure have become pregnant (40,41). The pregnancy experience with solid tissue transplant patients in general has found a 25% risk of maternal complications (with over half of these complications being hypertension), a 29% risk of miscarriage, and a 41% risk of prematurity (103). The best data specific to cardiac transplantation describes 32 U.S. pregnancies in women who had undergone cardiac transplantation, and found a 44% rate of hypertension, a 22% risk of rejection, and a 13% risk of worsening renal function. Neonatal complications were similar to the data described above for all solid tissue transplants (104). In light of these data, women who have undergone cardiac transplantation are warned of the possible risks of a pregnancy, and are encouraged to wait 2 years after transplantation before becoming pregnant to ensure that the transplant has been a success. Drugs used to prevent rejection should be continued during pregnancy; evidence of their safety is accumulating. If antirejection treatment is continued, pregnancy does not appear to increase the risk of rejection (104,105). The peripartum management should be dictated by the quality of left ventricular function in a manner similar to that discussed previously in this chapter.
Cardiopulmonary Resuscitation
Pregnancy poses some unique problems during cardiopulmonary resuscitation (CPR). In the third trimester and particularly near term, the gravid uterus impairs venous return. Thus, during CPR, the uterus should be displaced (i.e., left uterine tilt). Moreover, if defibrillation is required, the left breast needs to be displaced because of marked enlargement during pregnancy. The unlikely but theoretical possibility that there may be electrical arcing between a defibrillator and any fetal monitoring devices means that fetal monitoring devices should be removed prior to defibrillation. Otherwise, the Advanced Cardiac Life Support (ACLS) protocols, including medications and the use of the defibrillator, should be followed as done in a nonpregnant patient. Some experts would suggest that the use of amiodarone should be deferred in cardiac resuscitation until alternative appropriate agents have failed. However, in the context of a cardiac arrest, this author would support the use of any recommended ACLS medication, as the one-time use of any of these agents is very unlikely to be of any harm, and may be of great benefit to both mother and fetus.
Data about the risk and benefits of an emergency cesarean delivery in the context of maternal resuscitation are very limited. The present-day view is that if the fetus has reached a point in the pregnancy where survival after delivery is possible (typically more than 24 weeks' gestation), emergency cesarean should be considered a part of the resuscitative efforts. Evacuation of the gravid uterus, with the concomitant release of pressure on the inferior vena cava and removal of the low-resistance circulatory unit that is the placenta, may improve the efficacy of chest compressions and improve the outcome for both mother and baby. Present recommendations are for consideration of cesarean delivery in pregnant women greater than 24 weeks' gestation who have had a cardiac arrest and failed to respond to 5 minutes of aggressive and appropriate resuscitative efforts (106).
An extensive review of this topic is available on the American Society of Anesthesiology website.
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