Respiratory Problems In Pregnancy

MAISSA SHARAFELDIN,phd,fccp Prof. of Pulmonary Medicine Faculty of Medicine, Cairo University

INTRODUCTION

The respiratory system undergoes a number of anatomic and physiologic changes during the course of a normal pregnancy. Some of these changes may predispose the patient to developing several acute pulmonary disorders, such as aspiration, thromboembolic disease, pulmonary edema, and amniotic fluid embolism. Pregnancy can also affect the course of some chronic pulmonary diseases, most notably, asthma. Conversely, these pulmonary conditions, if poorly controlled, can adversely affect pregnancy. This chapter describes these anatomic and physiologic alterations, and reviews the clinical presentation and treatment of acute and chronic pulmonary diseases that occur during pregnancy. CARDIORESPIRATORYPHYSIOLOGY AND PREGNANCY A number of anatomic and physiologic changes that occur during pregnancy affect the cardiorespiratory system. The upper airway becomes hyperemic, leading to nasal obstruction, increased mucous secretion, and occasionally epistaxis(1). These changes may be more pronounced in patients with preexisting atopic disease, chronic sinusitis, or preeclampsia, and they are more evident during the thirdtrimester. Blood volume gradually increases from the 6th week to the end of pregnancy, when it is approximately 40% above normal(2,3). The increase is largely due to increased plasma volume, as red blood cell mass remains the same. The result is hemodilution, anemia, and decreased serum protein levels (4). Extracellular fluid also increases, contributing to peripheraledema(5,6). Cardiovascular changes include an increased heart rate, increased stroke volume, and decreased peripheral resistance with an attendant increase in cardiac output (7,8,9,10,11,12). The increase in stroke volume begins around the 10th week and peaks at 20 to 24 weeks, where it is maintained until term (3,13,14). Heart rate begins to increase at 5 to 12 weeks, reaching a maximum value of 10% to 30% above prepregnancy values at 32 weeks (9,10,11,12). In the supine position, the gravid uterus compresses the inferior vena cava, causing decreased venous return and consequently a lower stroke volume and cardiac output. This does not occur in the left lateral decubitus position(13,14). Because of lower systemic vascular resistance, systemic blood pressure may be lower, most notably in midpregnancy. The decrease in diastolic pressure is greater than the decrease in systolic pressure, and hence there is a widened pulse pressure (13,14). Blood pressure generally rises during pregnancy but usually remains below prepregnancy levels. Central venous pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure generally do not change duringpregnancy (12). The anatomic changes of pregnancy also affect pulmonary function (Fig. 1). As the uterus enlarges it can cause up to a 4 cm elevation of the diaphragm, although it does not appear to affect diaphragmatic function (15,16). The anteroposterior and transverse diameters of the thoracic cage also increase by 2 cm, in part offsetting the volume loss due to diaphragm elevation (17). Because the diaphragm is displaced upward, there is a decrease in residual volume and expiratory reserve volume, resulting in a decreased functional residual capacity. Conversely, inspiratory capacity and tidal volume increase, so that vital capacity and total lungcapacity remain the same The effect of pregnancy on pulmonary function. There is a gradual decrease in residual volume ( RV) and functional residual capacity ( FRC ), while vital capacity ( VC) and total lungcapacity ( TLC) remain the same. Usually, spirometric measurements of the forced expiratory volume in one second (FEV1), forced vital capacity, and flow rates do not change (4,18,19,20,22). Likewise, there are no changes in lung compliance in a normal pregnancy (23). There may be a slight increase in the carbon monoxide diffusing capacity during early pregnancy, although it usually decreases to normal or slightly below normal as pregnancy progresses (24). The mechanism of these changes isunclear. A 20% to 50% increase in minute ventilation occurs toward the end of the first trimester and remains constant throughout pregnancy. The increase is thought to be caused by increased progesterone levels, (15,18,25,26) and is related to an increase in tidal volume rather than an increase in respiratory rate (7). The arterial oxygen tension is usually greater than 100 during pregnancy, although it may decreasecloser to term (28-38). DYSPNEA IN THE PREGNANTPATIENT Dyspnea is a common complaint during pregnancy, affecting 60% to 70% of women with no previous history of cardiac or pulmonary disease.18,21,39,40 Although the etiology is unknown, it is thought to be related to physiologichyperventilation.40 Physiologic dyspnea usually occurs early in pregnancy and improves closer to term. Patients are able to perform daily activities and are usually not dyspneic with rest. Pathologic dyspnea, however, usually worsens with time and it is often due to upward displacement of the diaphragm (13,41,42,43). ACUTE PULMONARY DISEASE IN PREGNANCYPneumonia Pneumonia, although infrequent, is the most common nonobstetric infection to cause complications as well as maternal and fetal mortality in the peripartum period (44). The microorganisms that cause pneumonia in the pregnant patient are not unique; however, pregnant women may be more susceptible to organisms that are controlled by cell-mediated immune processes, such as viruses, fungi, and mycobacteria (45). For example, pregnant patients had a higher mortality rate due to influenza A during the 1918, 1957 and H1N1 epidemics. Coccidioidomycosis is the most extensively studied fungal infection in pregnancy. Although coccidioidomycosis is rare and does not affect the outcome of pregnancy unless it becomes disseminated, several studies suggest that the risk of dissemination is higher in pregnant women than in the general population, especially in the third trimester (46,47-64).BACTERIAL PNEUMONIA. Fever, chills, and cough productive of purulent sputum are the most common complaints in bacterial pneumonia. The two most common bacterial pathogens include Streptococcus pneumoniae (Pneumococcus) and Haemophilus influenzae. Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae also occur, but their incidence in pregnancy is unknown. When bacterial pneumonia complicates viral pneumonia,Staphylococcus aureus or gram- negative organisms should beconsidered as potential pathogens. Most community acquired pneumonias can be treated in the outpatient setting with an orally active antibiotic, preferably one that is penicillin-related or a cephalosporin. Erythromycin should be added if Mycoplasma or Legionella are a concern. These antibiotics are classified as category B by the Food and Drug Administration (FDA). If the patient appears severely ill, however, hospital admission should be considered and antibiotics should be administered intravenously. Intravenous aminoglycosides, used for gram-negative bacteria, can cause toxicity to fetal auditory function. Vancomycin, which should be used only for resistant gram-positive infections, may cause renal and auditory nerve damage to the fetus. Antibiotics to be avoided in pregnancy include tetracycline, which can affect fetal skeletal and dental development; chloramphenicol, which can cause newborn “gray syndrome”; and trimethoprim with sulfamethoxazole, which can interfere with folic acid metabolism and has caused cleftpalates in rats (47). Aspiration Pneumonia Aspiration pneumonia is a significant cause of maternal morbidity and mortality. Factors that predispose the pregnant patient to aspiration during labor and delivery include increased intragastric pressure caused by abdominal compression, decreased gastroesophageal sphincter tone due to progesterone effects, delayed gastric emptying, repeated abdominal palpations during examinations, and alteration of consciousness secondary to analgesics and anesthesia (47,73). Most cases of aspiration occur if general anesthesia or endotracheal intubation is needed. Aspiration of gastric acid is usually followed by chemical pneumonitis and pulmonary edema due to increased vascular permeability. The clinical presentation includes tachypnea, cyanosis, hypoxemia, hypotension, tachycardia, and bronchospasm. The chest radiograph shows either isolated or diffuse infiltrates. Large volumes can cause immediate asphyxiation. The pH of the aspirate is also important. Minimal injury has been found whenthe pH is greater than 2.5 (74). The treatment of aspiration pneumonia is supportive, and consists of oxygen, bronchodilators, and if needed, ventilatory support. (75); however, the condition may also progress to respiratory failure and ARDS.Tuberculosis Tuberculosis (TB) is caused by inhalation of aerosol droplets carrying the organism. Tubercle bacilli multiply in the lung and migrate via the lymphatic and cardiovascular system to other organs including the spleen, liver, bones, meninges, joints, genitalia, endometrium, and placenta. The incidence of mycobacterial disease has increased in recent years, possibly because of the increased rate of HIV infection, increased numbers of immigrants from endemic countries, and a decline in public health services Diagnosis is usually obtained by direct smear and culture from expectorated sputum (67,68,69,70) Treatment in nonpregnant patient involves four medications: isoniazid, rifampin, and pyrazinamide plus either streptomycin sulfate or ethambutol. Since streptomycin sulfate can interfere with fetal auditory development and can cause congenital deafness, its use is not recommended in the pregnant patient. Although there are no data on the teratogenicity of pyrazinamide, it should be avoided if possible in the pregnant patient. The pregnant patient, who is not at high risk for drug-resistant TB, should be treated with isoniazid, rifampin, and ethambutol for a total of 9 months. If the risk of drug resistance is high, pyrazinamide may be added with the understanding there are unknown risks. Pyridoxine should be given to all patients receiving isoniazid toavoid nerve damage to the mother. Congenital TB of the newborn occurs as a result of placental transmission to the fetus via the umbilical vein or by aspiration of infected amniotic fluid (71). A tuberculin skin test is usually negative in the newborn, but it may turn positive after 1 to 3 months (67). Congenital TB has a high mortality rate, especially if there is a delay in establishing the diagnosis andstarting antibiotic therapy (72-78). Deep Vein Thrombosis and Pulmonary Embolism There is similar risk for venous thromboembolism (VTE) in all 3 trimesters of pregnancy, although the incidence of deep venous thrombosis (DVT) is approximately 3 times higher than that of PE during pregnancy. Pulmonary embolism (PE) is a leading cause of death among pregnant women in the developed world. The fact that PE remains such a threat is a clear indication of the difficulty in diagnosing it. The coexistence of pregnancy makes the workup and management of PE even more problematic, for many reasons. First, there are 2 patients at risk rather than 1. Second, overdiagnosis results in unnecessary, dangerous treatments that jeopardize both patients and makes the pregnancy and delivery far more complicated. Third, the usual imaging modalities, which we use without a second thought in nonpregnant patients, suddenly become more complicated inpregnant patients. All 3 elements of Virchow's triad are present during pregnancy and the early postpartum period; they are hypercoagulability, vascular damage, and venous stasis. Pregnant patients are at increased risk for thromboembolic disease for several reasons: (1) decreased venous tone and blood flow in the lower extremities, leading to venous stasis (80,81); (2) compression of the inferior vena cava and left iliac vein by the uterus, leading to venous outflow obstruction and stasis (81,82); and (3) an increase in several clotting factors and a decrease in fibrinolytic activity, leading to a hypercoagulable state(83). A normal D-dimer level appears to have a high negative predictive value in patients with a low clinical suspicion for VTE, but false-positive levels are very common.The decision to use imaging modalities that produce radiation exposure in pregnant patients is difficult because of concerns with teratogenicity. Radiation exposure of 1 Gy at any stage of pregnancy is regarded as the level above which the risk for induction of congenital abnormalities is possible. The following is a list of imaging tools commonly used in PEdiagnosis. Clinical symptoms of pulmonary embolism (PE) include the sudden onset of dyspnea, tachypnea, tachycardia, and pleuritic chest pain. In massive PE, arrhythmias, syncope, and cardiovascular collapse may develop. The best diagnostic test to diagnose PE is the pulmonary angiogram, although it has the disadvantage of being an invasive test (88,89). Ventilation and perfusion lung scanning is a reliable noninvasive test used to determine the presence of PE, but the results may be difficult to interpret in some cases. While a normal scanexcludes PE (90) and a high- probability scan usually indicates PE, approximately 40% to 70% of all patients have scans interpreted as low to intermediate probability (88,91,92). The presence of a DVT increases the likelihood that thepatient has a PE. Treatment of DVT and PE involves the use of anticoagulants. Since warfarin is contraindicated in pregnancy, heparin is the drug of choice. Heparin can be given by intravenous infusion or subcutaneously, and the dose should be adjusted by maintaining the patient's partial thromboplastin time at a level 1.5 to 2.5 times the control. Treatment should be given for the duration of pregnancy and continued for approximately 4 to 6 weeks after delivery. If thrombosis occurs late in the pregnancy, treatment may be required for up to 3 months after delivery. Patients who have a history of a previous DVT or PE can be managed prophylactically by either empiric treatment with subcutaneous heparin at a dose of 5000 units every 12 hours or by weekly surveillance with impedance plethysmography or duplex ultrasonography (93,94,95,96). Pregnancy is a relative contraindication to the use of thrombolytic therapies such as streptokinase, urokinase, and tissue plasminogen activator, and these should be used only in patients suffering from massive PE and cardiovascular instability (98,99,100). The use of vena cava filters is indicated for those patients who cannot be anticoagulated or for those who have recurrent PE whileon adequate anticoagulant therapy. Other acute catastrophic respiratory problems inpregnancyAthough rare they are fatal as; - Amniotic Fluid Embolism(101-105). - Tocolytic-Induced Pulmonary Edema (106-110). - Adult Respiratory Distress Syndrome(111-117)Asthma Asthma affects approximately 7% to 10% of adults of all ages and is one of the most common medical conditions complicating pregnancy (118). Asthma may develop de novo during the childbearing years, or it may exist as a persistent abnormality sincechildhood In many patients, adult- onset asthma actually represents a recurrence of disease that was originally present during childhood but went into remission during adolescence (119). For unknown reasons, asthma severity appears to be greater in women versus men between the ages of 20 and 50years (120). Experience suggests that pregnancy has a variable effect on the course of asthma. Different studies have suggested that asthma may improve, worsen, or remain the same during pregnancy (121,122,123,124). As a rule, however, women with severe asthma before pregnancy are at greater risk of having their asthma worsen during pregnancy (121,122,123,124). Moreover, the effect of pregnancy on asthma symptoms is likely to be consistent during successive pregnancies in an individual patient (122,125). Although unproven, it is suspected that hormonal changes associated with pregnancy may be related to improvement in symptomsin some patients. Pregnancy- associated deterioration in asthma, however, may be linked to an increased incidence of viral respiratory infections, increased gastroesophageal reflux, and changes in glucocorticoid-receptor responsiveness. It also seems likely that the changes in ventilatory mechanics that occur during pregnancy (i.e., breathing at low lung volumes, where some airways are closed or near closure) may result in increased symptoms when superimposed on the underlying airway obstruction associatedwith asthma. Some studies suggest that asthma may have an adverse effect on pregnancy in terms of an increased rate of preterm births, decreased birth weight, and increased rates of neonatal and maternal mortality(126,127). Although other factors may be involved, poor asthma control seems the most likely explanation for these epidemiologic findings(128). Patients with impaired pulmonary function or those requiring hospitalizations for asthma during pregnancy tend to have infants with lower birth weight than asthmatics whose disease is better controlled(129,130). Although the mechanisms for these findings are unclear, maternal hypoxia and alkalosis due to hypocapnia and the hyperventilation of pregnancy mayplay a role.MANAGEMENT. It is important to note that asthma is heterogeneous with respect to severity, natural history, and response to therapy. Accordingly, therapy should be tailored to the individual patient, monitored regularly, and adjusted to meet thecurrent level of severity. Although pharmacologic therapy is a vital component of good management, patient education and avoidance of asthma triggersare also important. Goals of asthma therapy inpregnancy :• Control of asthma is essential• Monitor symptoms by PEFR • Educate the patient to avoidtriggers• Medicate appropriately• Avoid hospitalization• Avoid acute severe asthma • Prevent/avoid side effects ofmedications for mother/fetus •Establish communication between you and doctor managing pregnancy The medication used in asthma exacerbation during pregnancy areessentially the same as in non- pregnant asthmatics. The difference is that now fetal health is important as well. Untreated asthma represents more risk to both motherand fetus than any drug treatment. Drugs currently available to treat asthma may be classified as “reliever” or “controller” agents, depending on their principalpharmacodynamic effect. Short- acting bronchodilators such as inhaled β-agonists are considered reliever agents, because they are to be taken for acute symptom relief on an as-needed basis. Corticosteroids, leukotrine receptor modifiers, sustained-release theophylline, and long-acting β-agonists are considered controller agents, because they are used to achieve and maintain control of symptoms and are used daily on a long-term basis. In general, medications that are commonly used for chronic management of asthma may be taken safely by thepregnant patient (131,132,133). Inhaled β2-adrenergic agonists are the drugs of choice foracute symptoms (134). Short- acting β-agonists provide rapid bronchodilatation and have a 3- to 6-hour duration of activity. Tachycardia, palpitations, and tremor may be seen with excessive dosing, and hypokalemia may occur at even higher doses. There is no evidence that their use is associated with adverse outcomesfor the mother or fetus (135). Long-acting inhaled β-agonists (LABA) have at least a 12-hour duration of activity and are considered controller agents and should be given twice daily on along-term basis Theophylline was used for many years as first-line treatment for asthma. More recently, however, slow-release theophylline has been used primarily as added therapy in patients whose symptoms fail to abate with inhaled corticosteroids. Theophylline has relatively weak bronchodilator activity in therapeutic doses, and recent evidence suggests that it may also have anti-inflammatory properties (136). Recent studies have shown that the use of slow-release theophylline during pregnancy was not associated with an increased risk of premature contractions, placenta previa, placental abruption, prolonged third phase of delivery, or postpartum hemorrhage (137). In the same study, an increased incidence of preeclampsia and neonatal jaundice was observed in asthmatics taking theophylline, compared to asthmatics not taking theophylline and to nonasthmatic pregnant controls. Patients who are taking theophylline may also breastfeed, since less than 1% of the theophylline diffuses fromplasma to breast milk (138). Glucocorticoids are the most effective agents available for moderate to severe asthma (139). Glucocorticoids are available for systemic or inhalational use. Side effects such as adrenal suppression, osteoporosis, weight gain, hypertension, diabetes, dermal thinning, cataracts, myopathy, and psychotic reactions are dose related and are usually seen with systemic steroids. Local side effects, including oral thrush and dysphonia, may occur at lower doses of inhaled glucocorticoids. Although chronic use of oral or systemic glucocorticoids has been associated with decreased birth weight,140 similar effects have not been reported with inhaled glucocorticoids. Optimal management requires a stepwise approach to drug therapy based on disease severity.141 Such an approach recognizes that severity may vary over time, and it considers treatment an ongoing process whereby increments and decrements in therapy are made in accordance with changes in severity. Although errors in management are often related to undertreatment with drugs, overtreatment can also be a problem, especially in patients with moderate to severe asthma, who tend to remain on a static treatment regimen even after they have achieved symptom control and clinical stability. Principles of management in the pregnant asthmatic patient have been thoroughly reviewed in the Report of the Working Group on Asthma and Pregnancy, written by an expert panel of specialists in obstetrics and gynecology, pulmonology,allergy, and pharmacology (142). Safety of asthma drugs inpregnancy (143-151): - Terbutaline and Formeterol: safe drugs Category B - Salbutamol and salmeterol: used only in life-threatening situations Category C - Epinepherine : It is used since 1956 without observed teratogeniceffect Category B - Theophyllines cross the placenta. It may prolong labor because it increase cAMP which inhibits uterine contractions. This has no clinical significance. It is excreted inbreast milk. It is Category B - Anticholinergics : safe drugsCategory B ASTHMA MANAGEMENTDURING LABOR AND DELIVERY. As a rule, asthma exacerbations are uncommon during labor and delivery (122). It is recommended that stable patients be given their usual medications during labor and delivery. In patients with uncontrolled asthma during labor, however, continuous electronic fetalmonitoring is advised. Oxytocin is not associated with bronchoconstriction and is therefore the drug of choice for labor induction. Analogs of prostaglandin F2α (PGF2α) and PGE2, however, are known to cause bronchospasm in asthmatics and should be avoided (152,153). For relief of pain and anxiety during labor, the narcotic analgesic fentanyl is preferred over morphine because of the histamine-releasing properties of the latter. Regional analgesia by the lumbar epidural approach is also recommended for asthmatics because it reduces minute ventilation, respiratory alkalosis, and increased risk of fetal hypoxia. If general anesthesia is required for surgical delivery, halogenated anesthetics in low doses are recommended because of their bronchodilator properties (156,157). Ketamine is the preferred anesthetic agent for use during induction, since it, too, has bronchodilator effects (158). If muscle relaxation is required, pancuronium is the preferred agent because of the histamine-releasing properties ofsuccinylcholine (159).CONCLUSION Physiologic dyspnea and hyperventilation are common symptoms of pregnancy, but they are usually benign and not reflective of serious underlying pathology. Several serious pulmonary complications of pregnancy may occur, however, and because they can adversely affect outcomes for both mother and fetus, physicians should be aware of their occurrence and familiar with prevention and treatment strategies. Thromboembolic disease, amniotic fluid embolism, aspiration, pneumonia, and pulmonary edema are the most commonly encountered serious complications. Chronic pulmonary diseases, most notably asthma and sarcoid, can adversely affect pregnancy if disease is poorly controlled; conversely, pregnancy can often affect the clinical course of patients with these chronic conditions. Although pregnant patients with pulmonary disorders are often treated with medications commonly used in the nongravid patient, the effects of many of these medications on pregnancy and fetal development are unknown. More studies of the effects of new therapies are needed in pregnant women to ensure patient access to the most effective treatments, and to provide knowledge of the risks ofsuch treatments (160).