Epidemiology

Asthma is one of the most common pulmonary problems in pregnant women; recent studies report that approximately 8% are affected.³ The disease is characterized by hyperactive airways leading to episodic bronchoconstriction. The role of inflammatory mediators in the pathogenesis of asthma has become apparent in recent years, leading to earlier use of inflammatory medications in the treatment of exacerbations.

The cause of asthma is unknown; however, it has been observed that its prevalence in the general population is increasing.

Effects of Asthma on Pregnancy

Asthma may be triggered by environmental allergens, medications, especially aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), or stress.⁴ Most exacerbations are marked by cough, wheezing, and dyspnea. Rapid therapeutic intervention at the time of an exacerbation is imperative to prevent impaired maternal and fetal oxygenation, because uncontrolled asthma can increase maternal morbidity. In several studies, even after controlling for confounding variables, adverse pregnancy outcomes are more pronounced in patients with asthma. These include low birth weight, preeclampsia, preterm birth, and stillbirth.^5,6

Whereas historical data have shown an increase in perinatal death and low birth weight,⁷ Fitzsimmons and colleagues observed low birth weight in only those patients treated for status asthmaticus.⁸ In addition, Schatz and colleagues noted that intrauterine growth restriction was directly related to lung function as measured by FEV₁.⁹

Effect of Pregnancy on Asthma

Numerous studies have observed that the course of asthma may be affected by pregnancy. Gluck et al. found that on average, asthma improved in 36% of women during pregnancy, remained unchanged in 41%, and worsened in 23%.¹⁰ Schatz et al., in an analysis of 366 pregnancies in which patient status was followed by objective criteria, found that asthma improved in 28%, remained unchanged in 33%, and worsened in 35%. Fifty-nine percent of the patients had similar asthma control in successive pregnancies.¹¹

Fetal sex may influence asthma in pregnancy. In one study, mothers who gave birth to boys were more likely to report improved asthma symptoms.¹² Dodds and colleagues also found that the use of medications to treat asthma was less common in mothers of boys.¹³ While a number of hypotheses have been proposed, including alterations in progesterone and the role of leukotrienes, changes in not one of these mediators can explain the varied course of the pregnant asthmatic.¹⁴

Management

The National Asthma Education and Prevention Program (NAEP) issued specific guidelines regarding asthma treatment. In 1993, the Working Group on Asthma and Pregnancy established criteria for diagnosis and treatment in the gravid population (Figure 160-2).¹⁵

Figure 160-2 Treatment during pregnancy.

The goals of treatment during pregnancy are to control exacerbation and prevent status asthmaticus, thereby reducing maternal and fetal hypoxemia. The initial step in treatment involves monitoring pulmonary function, and FEV₁ is the single best measure. Physical examination and chest radiography are poor measures of disease severity. A portable hand-held peak flowmeter gives a quick, accurate assessment by measuring the PEFR. Most authorities believe that airways remain essentially unchanged throughout pregnancy; therefore, every patient with asthma should be given a peak flowmeter and be educated in its use. The patient should obtain a baseline PEFR during a quiescent period. The severity of disease is determined by the occurrences of exacerbations and the changes in FEV₁ and PEFR. The PEFR can be used as a guide to refer the patient for emergency care.

Pharmacologic therapy is the mainstay of asthma treatment. Most drugs used in the treatment of asthma are thought to be safe in pregnancy. Inhaled β-agonists are the most frequently used in asthma treatment. A prospective study of inhaled β-agonists in 259 pregnancies showed no change in the rate of congenital malformation, perinatal mortality, low birth weight, or complications of pregnancy.¹⁶ There is little role for the use of oral β-agonists, which may have more adverse systemic symptoms and are no more effective than inhaled drugs.

Inhaled corticosteroid therapy remains the mainstay of antiinflammatory treatment of asthma. Corticosteroids have also been advocated as first-line therapy in patients with mild asthma.¹⁷ Studies have demonstrated that with asthma, those taking an inhaled corticosteroid were four times less likely than their nontreated counterparts to suffer an exacerbation.¹⁸ Another randomized study noted that there was a 55% reduction in readmission rates for acute asthma in patients using inhaled beclomethasone.¹⁹ Inhaled corticosteroids can increase the effectiveness of β-adrenergic agents by inducing the formation of new β receptors. Because beclomethasone is the most studied of the inhaled corticosteroids in pregnancy, it is recommended as first-line therapy.¹⁵ However, if patients are well controlled on other corticosteroid preparations, it is suggested they be continued on their current medication, because all inhaled corticosteroids are labeled by the U.S. Food and Drug Administration (FDA) as pregnancy class C. Other antiinflammatory medications used in the treatment of asthma (e.g., cromolyn sodium and nedocromil sodium) appear to be less effective than inhaled corticosteroids in reducing asthma symptoms.

Systemic corticosteroids should be reserved for the periodic treatment of acute asthma exacerbations. Chronic oral corticosteroid therapy may increase the risks of gestational diabetes mellitus, preterm labor, low-birthweight infants, and preeclampsia; however, it is evident that the benefits of controlled severe asthma outweigh the potential risks to the mother and fetus.

Intravenous corticosteroids have no increased benefits over oral corticosteroids in the treatment of acute exacerbations.²⁰ Methylprednisolone, hydrocortisone, and prednisone are safe for use in pregnancy, unlike betamethasone or dexamethasone, because very little active drug crosses the placenta.

Leukotriene pathway moderators have been shown to improve pulmonary function, as measured by FEV₁.²¹ Zafirlukast and montelukast are rated FDA category B; however, there is little experience with these drugs in pregnancy, and their role is undetermined.

The treatment of asthma requires patient education to provide optimization in the preconceptional period and during the pregnancy to provide optimum outcome. Box 160-1 offers a suggested schematic for the treatment of asthma in pregnancy.

Status Asthmaticus

Status asthmaticus is a rare complication in pregnancy. Diagnosis is established by a PaO₂ of less than 70 mm Hg, a PaCO₂ of greater than or equal to 35 mm Hg, or a measured expiratory flow of less than 25% of expected. Because of impending respiratory failure, these patients should be managed in a critical care unit. Aggressive treatment of status asthmaticus is mandatory to protect the mother and fetus. Maternal mortality may be as high as 7% and fetal mortality as high as 11% despite adequate treatment. Epinephrine is not contraindicated in pregnancy during a respiratory emergency. Criteria for intubation in the gravida with status asthmaticus include (1) inability to maintain PaO₂ of greater than 60 mm Hg despite supplemental oxygen; (2) inability to maintain a PCO₂ of less than 40 mm Hg; (3) evidence of maternal exhaustion, with worsening acidosis (pH < 7.2) despite intensive bronchodilator therapy; and (4) altered maternal consciousness.¹⁵

When traditional treatment proves to be ineffective, a number of therapies have been reported beneficial. The use of a helium-oxygen mixture that has been reported to be effective in nonpregnant studies has been used safely in pregnancy.²²

Etiology

There are a number of causes of pulmonary edema in pregnancy. Some are pathologic in their process, others are due to idiopathic causes. One of the most common associations with pulmonary edema during pregnancy is hypertensive disease. In patients with hypertensive disease, pulmonary edema may be cardiogenic due to fluid overload or left ventricular dysfunction, or noncardiogenic due to decreased oncotic pressure.

Another common cause of pulmonary edema in pregnancy is tocolytic therapy. Most cases described have resulted from the intravenous use of beta sympathomimetics. The use of magnesium sulfate therapy as well as the use of corticosteroids in association with tocolysis for preterm labor has been shown to exacerbate the condition. The incidence of edema is increased in multiple gestations and in patients with subclinical infection.

Other causes of acute pulmonary edema in pregnancy include amniotic fluid embolism, aspiration, and the need for massive transfusion after hemorrhage.²³

Treatment

The treatment of pulmonary edema during pregnancy depends on its etiology. Determination of the cause is best obtained by the use of pulmonary artery catheterization and measurement of pulmonary capillary wedge pressure. Although all patients may not require this intervention, it is recommended in patients in whom the clinical picture may be unclear (e.g., those with hypertensive disease) and in those who do not respond to standard diuretic therapy.

For patients who do not improve rapidly with diuretic therapy, intubation and ventilation with positive pressure is recommended. In addition to the use of diuretic therapy, reduction of preload and afterload may be achieved by the use of vasodilators such as nitrates, hydralazine, or calcium channel blockers. All are safe for use in pregnancy.

Box 160-2 offers a guide for treatment of patients with pulmonary edema.

Etiology

The causes of acute respiratory distress syndrome (ARDS)^24–27 in pregnancy include preeclampsia, sepsis, aspiration, pyelonephritis, intrauterine infections, acute fatty liver of pregnancy, and amniotic fluid embolism.²⁸ In a review of 83 cases of ARDS associated with pregnancy, it was noted that among the causes of ARDS, 35 cases were attributed to uniquely obstetric conditions.²⁹ In addition, it was noted that varicella pneumonia and pyelonephritis were associated with ARDS. These conditions rarely trigger ARDS in immunocompetent adults. De Vaciana et al. pointed out that development of lung injury in pregnancy correlates with known physiologic changes including increased blood volume, decreased colloid osmotic pressure, and an unchanged critical lung closing volume despite a diminished FRC.³⁰

Management

Management of ARDS includes diagnosis, maternal stabilization, fetal monitoring, investigation and treatment of underlying causes, and in many cases, evaluation for delivery.²⁹

Maternal stabilization includes intubation for mechanical ventilation if necessary. The clinician should consider intubation sooner rather than later in the presence of respiratory deterioration, keeping in mind that decreased FRC exacerbates respiratory distress.

Contemporary thinking regarding the treatment of ARDS has found that a lung-protective ventilator strategy is the first therapy that has been found to improve outcomes in ARDS. It has been noted in numerous studies that decreasing the VT from the standard of 12 mL/kg to 6 mL/kg or less and peak inspiratory pressures to less than 30 cm H₂O from 50 cm H₂O have resulted in decreased morbidity and mortality in patients with ARDS.³¹ There has been much discussion in the literature concerning permissive hypercapnia and its use in preventing lung injury. However, there have been no controlled studies in pregnancy, and it is the opinion of the author that increasing PaCO₂ in the pregnant patient should be undertaken with caution.

Judicious use of fluids is important in the management of ARDS. Although some authors have advocated the use of fluid restriction, the clinician must consider the volume-dependent status of pregnancy. It is recommended that fluid management be carefully guided by the use of hemodynamic monitoring.

Whereas oxygenation is important, it should be noted that oxygen should be used at the lowest concentration possible because it is toxic to lung tissue in high doses. The goal of therapy is to keep the SaO₂ ≥ 95%.

A number of other methods have been discussed in the treatment of ARDS, including inhaled nitric oxide, prostacyclin, surfactant, and inverse ratio ventilation. Currently these modalities cannot be recommended, because they have not been shown to decrease morbidity and mortality. Other trials considering prone ventilation and corticosteroids in late ARDS appear promising but have not been proven in large prospective randomized trials.^32–34

Fetal surveillance during ARDS may be more difficult because drugs used to sedate the mother can affect fetal heart rate and variability. Sedatives, anxiolytics, hypnotics, and nondepolarizing agents are not contraindicated in pregnancy. In addition, preterm contractions and labor may present a problem due to maternal hypoxemia. The clinician is cautioned against starting tocolytic therapy before achieving adequate maternal oxygenation. If tocolysis in needed, β-agonists such as terbutaline should be avoided because of the risk of increased pulmonary capillary permeability and increased demands on cardiac load. Magnesium sulfate is not strictly contraindicated but also may increase pulmonary capillary permeability. The use of NSAIDs may be the best choice for tocolysis because they have been proven to improve ARDS in animal models.²⁹ Consultation with a maternal-fetal specialist is recommended to assist the intensivist in caring for these complex patients.

The timing of delivery of the patient with ARDS is a question that must be addressed by the clinician. Some authors advocate delivery after maternal stabilization, citing the possible “therapeutic effect” of delivery. Whitty and colleagues failed to demonstrate any significant benefit to delivery.³³ It is this author’s opinion that delivery should be considered on a case-by-case basis, carefully weighing the risk/benefit ratio to the mother and fetus.

Box 160-3 represents a reasonable management scheme for the patient with ARDS.