Pregnancy

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Chapter 76 Pregnancy

The pregnant patient who has pulmonary disease is unique because of altered maternal physiology, the occurrence of diseases specific to pregnancy, and the need to consider two patients in all therapeutic decisions. This chapter focuses on the changes in pulmonary physiology associated with pregnancy, certain pregnancy-specific disorders, and other pulmonary problems encountered in the pregnant patient.

Pulmonary Physiology

Physiologic Changes in Pregnancy

Hormonal changes in pregnancy affect the upper respiratory tract and cause airway hyperemia and edema resulting in symptoms of rhinitis. Estrogens are likely responsible for many of these effects because they produce capillary congestion and mucous gland hyperplasia. Changes to the thoracic cage result from both the enlarging uterus and the hormonal effects producing ligamentous laxity. The diaphragm is displaced cephalad by up to 4 cm, but the potential loss of lung capacity is partially offset by an increase in the anteroposterior and transverse diameters and by widening of the subcostal angle (Figure 76-1). Despite these anatomic changes, diaphragmatic function remains normal, diaphragmatic excursion is not reduced, and the maximum transdiaphragmatic inspiratory pressures that can be generated near term are similar to values generated by patients who are not pregnant. The changes in the chest wall return to normal within 6 months of delivery, although the costal angle may remain widened.

These changes in the thorax produce a progressive decrease in functional residual capacity (FRC) by 10% to 25% by term (Figure 76-2). Residual volume decreases slightly, but the major change is in expiratory reserve volume. These alterations are measurable as early as 16 to 24 weeks of gestation and progress to term. The increased diameter of the thoracic cage and the preserved respiratory muscle function allow the vital capacity to remain unchanged, and total lung capacity decreases only minimally. Measurements of airflow and lung compliance are not affected, but chest wall and total respiratory compliance are reduced in the third trimester because of the chest wall changes and increased abdominal pressure. Inconsistencies in results reported for diffusing capacity during pregnancy likely arise from the effects of anemia, variable changes in intravascular volume, and the increase in cardiac output. A small increase may be noted in early pregnancy with a subsequent decrease to normal values by term.

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Figure 76-2 Physiologic changes in pregnancy. Shown are some of the physiologic changes that occur during pregnancy and the postpartum period.

(From Lapinsky SE, Kruczynski K, Slutsky AS: Critical care in the pregnant patient, Am J Respir Crit Care Med 152:427–490, 1995.)

Minute ventilation increases greatly in pregnancy, beginning in the first trimester and reaching 20% to 40% above baseline at term (Figure 76-2), produced mainly by an increase in tidal volume of approximately 30% to 35%. These changes are mediated by the increase in respiratory drive that results from elevated serum progesterone levels. A respiratory alkalosis with compensatory renal excretion of bicarbonate results, with arterial carbon dioxide tension (PaCO2) falling to 28 to 32 mm Hg and plasma bicarbonate falling to 18 to 21 mEq/L. Alveolar-arterial oxygen tension difference (PO2[A−a]) is similar to nonpregnant values, and mean PaO2 usually exceeds 100 mm Hg at sea level throughout pregnancy. Mild hypoxemia and an increased PO2(A−a) may develop in the supine position because of airway closure, because FRC diminishes near term. One study suggests that shunt is normally increased in the third trimester to approximately 15% and is not changed significantly by posture. Oxygen consumption increases, beginning in the first trimester, and reaches 20% to 33% above baseline by the third trimester because of fetal demands and maternal metabolic processes. The combination of a reduced FRC and increased oxygen consumption lowers oxygen reserve, which renders the pregnant patient susceptible to the rapid development of hypoxia in response to hypoventilation or apnea.

During labor, hyperventilation increases, and tachypnea (caused by pain or anxiety) may result in marked respiratory alkalosis, augmented in some patients by volume depletion or vomiting. Alkalosis adversely affects fetal oxygenation by reducing uterine blood flow. In some patients, severe pain and anxiety may lead to rapid, shallow breathing with alveolar hypoventilation, atelectasis, and mild hypoxemia. Achieving adequate pain relief with narcotics or epidural analgesia blunts the ventilatory response and can correct the gas exchange abnormalities associated with active labor. The pregnancy-associated changes in lung function reverse significantly in the first 72 hours postpartum and return to baseline within a few weeks.

Changes occur to the pregnant woman’s immune system, to facilitate tolerance to paternally derived fetal antigens. Some suppression of cell-mediated immunity occurs; maternal lymphocytes demonstrate a diminished proliferative response to soluble antigens and to allogeneic lymphocytes, and decreased numbers of T-helper cells have been documented. These effects are balanced by an intact or slightly enhanced humoral immune response. These alterations to maternal immunity result in a predisposition to more severe manifestations of some viral and fungal infections.

Complications and Disorders of Pregnancy

Pregnancy-Specific Disorders

Amniotic Fluid Embolism

Amniotic fluid embolism is a rare obstetric complication (between 1 in 8000 and 1 in 80,000 live births) that carries a mortality rate of 10% to 86% and may account for 10% of maternal deaths. Amniotic fluid embolism is usually associated with labor and delivery, but it may also occur with uterine manipulations or uterine trauma or in the early postpartum period. The mechanism seems to involve amniotic fluid that enters the vascular circulation through endocervical veins or uterine tears. Particulate cellular contents and humoral factors in the amniotic fluid produce acute pulmonary hypertension, predominantly by causing vascular spasm (Figure 76-3). Acute right ventricular dysfunction results from the increased afterload and myocardial dysfunction mediated by humoral factors, associated with secondary left ventricular (LV) failure. The cardiovascular changes of amniotic fluid embolism may resemble those of anaphylaxis, and sensitivity to amniotic fluid contents may be responsible.

The clinical presentation usually involves the sudden onset of severe dyspnea, hypoxemia, and cardiovascular collapse, often accompanied by seizures. Less common presentations include hemorrhage caused by disseminated intravascular coagulation (DIC) and fetal distress. Up to one half of patients may die within the first hour, and cardiac arrest during this period is common.

The diagnosis of amniotic fluid embolism is usually made on the basis of observing the typical clinical picture. Fetal squames in a wedged pulmonary capillary aspirate have been used to confirm the diagnosis, but this is not a specific finding. Less invasive diagnostic tests, such as maternal serum zinc coproporphyrin or sialyl-Tn levels, have been investigated but are not currently in use. The differential diagnosis includes septic shock, pulmonary thromboembolism, abruptio placentae (placental abruption), tension pneumothorax, and myocardial ischemia.

Preeclampsia and Pulmonary Edema

Pulmonary edema may rarely occur in association with preeclampsia (i.e., perhaps 3% of preeclamptic patients). The preeclamptic patient is usually volume-depleted, and pulmonary edema usually occurs in the early postpartum period, often associated with aggressive, intrapartum fluid replacement. Other factors that may contribute to the pathogenesis include reduced serum albumin, elevated LV afterload, and systolic and diastolic myocardial dysfunction (Figure 76-4). Increased capillary permeability may also occur, aggravated by concomitant conditions such as sepsis, placental abruption, or massive hemorrhage.

Pulmonary edema has been described in chronically hypertensive, obese, pregnant patients in whom preeclampsia develops. Diastolic LV dysfunction results from both the hypertension and the obesity, and pulmonary edema is precipitated by volume overload of pregnancy and hemodynamic stresses of preeclampsia.

Preeclampsia is characterized by hypertension, proteinuria, and peripheral edema, usually in the third trimester. The presentation of pulmonary edema is with acute respiratory distress in the preeclamptic patient, often in the early postpartum period.

Tocolytic Pulmonary Edema

Beta-adrenergic agonists, as well as several other drugs, including nifedipine, indomethacin, atosiban, and magnesium sulfate, may be used to inhibit uterine contractions in preterm labor. Use of these agents has become less common, however, because a number of studies have demonstrated that tocolysis does not improve neonatal outcome. A complication of these drugs during pregnancy, particularly the β-agonists, is the development of pulmonary edema. The frequency of tocolytic-induced pulmonary edema varies from 0.3% to 9%. Postulated mechanisms include prolonged exposure to catecholamines causing myocardial dysfunction, increased capillary permeability, large volumes of intravenous (IV) fluid administration (often in response to maternal tachycardia), reduced osmotic pressure, and hypotension induced by β-adrenergic stimulation. Glucocorticoids are often administered in preterm labor to enhance fetal lung maturity and may compound fluid retention.

The clinical presentation is of acute respiratory distress with features of pulmonary edema. No specific features characterize tocolytic pulmonary edema. The diagnosis is a clinical one, made in the presence of acute pulmonary edema occurring in the appropriate clinical situation. The differential diagnosis includes cardiogenic pulmonary edema, amniotic fluid embolism, and other conditions (Table 76-1). Failure of the pulmonary edema to resolve in 12 to 24 hours requires a search for alternative causes.

Table 76-1 Acute Respiratory Distress Caused by Complications of Pregnancy and Labor

Disorder Distinguishing Features
Amniotic fluid embolism Cardiorespiratory collapse, seizures, disseminated intravascular coagulation
Pulmonary edema caused by preeclampsia Hypertension, proteinuria
Tocolytic pulmonary edema Tocolytic administration, rapid improvement with discontinuation
Aspiration pneumonitis Vomiting, aspiration
Peripartum cardiomyopathy Gradual onset, signs of heart failure
Venous thromboembolism Evidence of deep venous thrombosis; radiologic investigations
Pneumomediastinum Occurs during delivery; subcutaneous emphysema
Air embolism Related to sexual intercourse or cesarean section; associated hypotension

Other Pulmonary Disorders in Pregnancy

Asthma

Asthma affects 5% to 10% of the population and is therefore the most common pulmonary disorder in pregnancy. During pregnancy, the altered hormonal milieu may affect asthma control variably; patients may improve, worsen, or remain unchanged. Although pregnancy does not affect airflow in normal subjects, airway hyperreactivity in asthmatic subjects can be increased. Asthma severity usually returns to prepregnancy levels within 3 months postpartum.

The clinical features of asthma during pregnancy are the same as those in patients who are not pregnant. To differentiate from the dyspnea of pregnancy, objective assessment that uses pulmonary function tests to assess the degree of airflow limitation is essential. Gastroesophageal reflux (GER) is increased in both frequency and severity during pregnancy, and the symptoms of GER should be sought as a contributing factor.

Treatment and Prognosis

Management of the pregnant patient with asthma is similar to that in patients who are not pregnant and includes adequate monitoring, avoidance of precipitating factors, and patient education.

Although physicians may be reluctant to prescribe medications during pregnancy, poorly controlled asthma is potentially more dangerous for the fetus. Inhaled corticosteroids remain the mainstay of therapy, and are considered safe in pregnancy in moderate or low doses (Table 76-2). One study suggests a small increased risk of congenital malformation in women using high-dose therapy in the first trimester. The use of a spacer device is encouraged to reduce local side effects and systemic absorption. Although animal data suggest a small risk of cleft palate with systemic corticosteroid use, this has not been demonstrated in humans. Short courses of prednisone should be used to manage poorly controlled asthma when clinically indicated. Inhaled β-agonists seem safe and should be used as required for symptomatic relief. GER, a potentially preventable cause of worsening asthma, is frequently overlooked. Antireflux measures may greatly reduce asthmatic symptoms. Acute attacks are treated by ensuring adequate oxygenation, closely monitoring the fetus, and administering appropriate medications. Concerns over fetal effects of drugs should not cause physicians and patients to avoid use of effective pharmacologic therapy. Updated management algorithms are available through the Working Group on Asthma and Pregnancy of the National Asthma Education and Prevention Program (NAEPP).

Table 76-2 Safety Classification of Asthma Therapy in Pregnancy

Drug FDA Class
Inhaled bronchodilators  
Albuterol (salbutamol) C
Terbutaline B
Ipratropium B
Salmeterol C
Formoterol C
Tiotropium C
Inhaled corticosteroids  
Beclomethasone C
Budesonide B
Fluticasone C
Leukotriene antagonists  
Zafirlukast B
Montelukast B
Other agents  
Theophylline C
Cromolyn B
Systemic corticosteroids C

Data from U.S. Food and Drug Administration (FDA) classification of drug safety in pregnancy; note that the FDA is in the process of revising this approach to labeling. Categories are as follows: A, Human studies fail to demonstrate fetal harm. B, Animal studies fail to demonstrate harm, but no human studies or animal studies demonstrate risk not shown in human studies. C, Animal studies demonstrate risk, or insufficient data available; drugs may be used if benefit outweighs risk. D, Human studies demonstrate risk; drugs may be used if benefits justify the risks. X, Contraindicated in pregnancy.

Poor asthma control has been reported to increase the incidence of preterm birth, low birth weight, and perinatal mortality. Acute exacerbations may be associated with hypoxemia, which in turn may compromise the fetus.

Pulmonary Thromboembolic Disease

The incidence of venous thromboembolic disease related to pregnancy is 200 per 100,000 woman-years. The incidence is five times greater in the postpartum period than during pregnancy, and it remains an important cause of maternal mortality. Pulmonary embolism results from a hypercoagulable state associated with pregnancy, as well as from hormonally mediated venous stasis and local pressure effects of the uterus on the inferior vena cava (IVC). Pulmonary embolism occurs more frequently in the early postpartum period than during pregnancy, particularly after cesarean section.

The presentation is similar to that in the patient who is not pregnant. However, the clinical diagnosis of deep venous thrombosis (DVT) and pulmonary embolism is notoriously inaccurate. An overwhelming predilection for DVT in the left leg in the pregnant patient results from anatomic factors.

Investigation of suspected pulmonary embolism follows a similar approach to that in the patient who is not pregnant, and the diagnosis must be pursued aggressively. Duplex ultrasonography is useful for the diagnosis of DVT, although venous Doppler can give false-positive results because of venous obstruction by the gravid uterus. Ventilation-perfusion scanning can be performed with less than 0.5 mGy (<50 mrad) exposure to the fetus and, if necessary, a computed tomography (CT) pulmonary angiogram may be performed with similarly low fetal exposure (Figure 76-5). Teratogenicity is generally thought to require exposure greater than 50 to 100 mGy (5-10 rad), but an increased incidence of childhood leukemia may occur with fetal radiation exposures of 20 to 50 mGy (2-5 rad).

The use of radiologic investigations during pregnancy remains a concern for the fetus. However, the risk perceived by pregnant women and their husbands usually far exceeds the actual risk, and it is important to allay these concerns. It is important to establish a diagnosis of pulmonary embolism because of the major implications if such a diagnosis is missed and the potential effects of unnecessary therapy on the health of mother and fetus.

Treatment and Prognosis

Warfarin therapy during the first trimester has been associated with an embryopathy, and central nervous system abnormalities have been described with second- and third-trimester exposure. Accordingly, warfarin is usually avoided (Table 76-3). The anticoagulant of choice is heparin, which does not cross the placenta, is not associated with adverse fetal outcome, and can be readily reversed. Low-molecular-weight (LMW) heparins do not seem to cross the placenta and are both safe and effective in pregnancy.

Table 76-3 Management of Thromboembolic Disease in Pregnancy

Therapy FDA Class* Comments
Heparin C Bone demineralization after prolonged use
Low-molecular-weight heparin B/C Good evidence of safety
Warfarin D/X Teratogenic, central nervous system abnormalities and bleeding occur, although the risk appears low
Sometimes used in second trimester
Alteplase (r-tPA) C Consider in acute, life-threatening situations

* See Table 76-2 for U.S. Food and Drug Administration classification of drug safety in pregnancy.

When administered with adequate precautions, streptokinase, urokinase, and tissue plasminogen activator (tPA) have been used successfully without major hemorrhagic complications or significant adverse effects on the fetus or placenta. Nevertheless, use of these agents should be limited to life-threatening situations. When clinically indicated, an IVC filter can be placed transvenously, although there is some risk of dislodgment because of the dilated venous system and pressure effects during labor.

Women who have a known hypercoagulable state and those with a previous thromboembolism are at increased risk and should receive prophylaxis with anticoagulation throughout pregnancy.

Lower Respiratory Tract Infections

Lower respiratory tract infections are an infrequent occurrence but an important cause of indirect obstetric death. The pregnant patient is susceptible to the usual bacterial pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae and is at increased risk of complications such as respiratory failure and empyema. Pregnant women are at increased risk of developing severe respiratory disease related to influenza, particularly the 2009 pandemic H1N1 strain. Less common infections such as varicella pneumonia and coccidioidomycosis may be associated with more severe disease than in nonpregnant patients. These effects are caused by subtle changes in cell-mediated immunity as a result of the pregnant state. Pneumocystis jirovecii (previously P. carinii) pneumonia may be seen in human immunodeficiency virus (HIV)–positive patients. Pregnancy does not seem to affect the course or incidence of reactivation of tuberculosis.

The clinical features of lower respiratory infection are similar to those in nonpregnant patients. Although dyspnea and increased minute ventilation are common in pregnancy, the respiratory rate is not significantly elevated by the pregnant state.

A chest radiograph is essential for the diagnosis of lower respiratory tract infections and must be considered in any pregnant woman who has a clinical presentation suggestive of pneumonia. Delayed radiography may be partly responsible for the increased morbidity in the pregnant patient population. Further diagnostic investigations include the usual microbiologic cultures, sputum microscopy, and serologic tests as indicated.

Treatment and Prognosis

Usual antibiotic guidelines may be followed, although tetracyclines should be avoided in pregnancy. Quinolones are usually avoided in pregnancy because of an association with arthropathy, but the risk seems to be low. Pregnant women should receive the influenza vaccine, and if disease occurs, treatment with oseltamivir is appropriate. Treatment of varicella pneumonitis is with acyclovir, which decreases mortality and has not been associated with fetal anomalies. Coccidioidomycosis is associated with an extremely high mortality rate, and disseminated disease should be treated with antifungal agents. P. jirovecii pneumonia requires treatment with trimethoprim-sulfamethoxazole with folate supplementation, as well as with corticosteroids, if indicated clinically. Although folic acid antagonists and sulfa drugs carry risks for the fetus, pentamidine is associated with higher risks for mother and fetus. Tuberculosis treatment is with isoniazid and rifampin (rifampicin), which have a low risk of adverse fetal effects, as well as ethambutol initially, until sensitivities are available. Pyrazinamide has been used in pregnancy and is recommended by some authorities.

Although pneumonia is associated with an increased risk of mortality, this is probably attributable to underlying diseases rather than to the pneumonia. Fetal complications may occur, as may preterm labor. Transplacental transmission of varicella-zoster virus (VZV) occurs infrequently (<5%) but can produce limb deformities and neurologic involvement. The nonimmune pregnant woman exposed to VZV should receive prophylaxis with VZV immunoglobulin within 96 hours of exposure, as well as acyclovir if clinical disease develops. Unlike the treatment of active disease, tuberculosis prophylaxis can usually be deferred until after pregnancy, except in the case of recent exposure or skin test conversion.

When investigating and managing lower respiratory tract infections, it is important to consider effects on the fetus (radiation exposure, drug toxicities), but necessary evaluations and interventions should not be avoided inappropriately.

Acute Respiratory Distress Syndrome in Pregnancy

The pregnant patient is at risk for development of ARDS from a number of pregnancy-associated problems (Box 76-1). Gastric acid aspiration is a particular risk because of the increased intraabdominal pressure, reduced lower esophageal sphincter tone, and supine position during delivery. Iatrogenic factors such as excessive fluid administration and tocolytic therapy may contribute, as well as reduced albumin level.

The clinical features are similar to those in the nonpregnant patient. The diagnosis is by the usual criteria of hypoxemia in the presence of diffuse pulmonary infiltrates and in the absence of LV failure. A detailed history is critical for identification of the underlying problem.