Lung & Pregnancy

Lungs & Pregnancy In Health & Disease: 

Lungs & Pregnancy In Health & Disease

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Introduction: Pregnancy induces profound changes in the mother, resulting in significant alterations in normal physiology. The anatomical & functional changes affect the respiratory & cardiovascular systems. Management of respiratory diseases in pregnancy requires an understanding of these changes for interpretation of clinical & laboratory manifestations of disease states.

Respiratory Physiology: 

Respiratory Physiology

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Anatomical Changes : Hormonal changes in pregnancy affect the URT & airway mucosa, producing hyperemia , mucosal edema , hypersecretion , & increased mucosal friability. Estrogen is responsible for producing tissue edema , capillary congestion , & hyperplasia of mucous glands. The enlarging uterus & the hormonal effects produce anatomical changes to the thoracic cage. As the uterus expands, the diaphragm is displaced cephalad by as much as 4 cm ; the A/P & transverse diameter of the thorax increases , which enlarges chest wall circumference. Diaphragm function remains normal , & diaphragmatic excursion is not reduced.

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Pulmonary Function : Anatomical changes to the thorax produce a progressive decrease in FRC , which is reduced 10-20% by term. The RV can decrease slightly during pregnancy, but this finding is not consistent; decreased expiratory reserve volume definitely changes. The increased circumference of the thoracic cage allows the VC to remain unchanged, & the TLC decreases only minimally by term. Hormonal changes do not significantly affect airway function. Pregnancy does not change lung compliance, but chest wall & total respiratory compliance are reduced at term.

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Ventilation : The MV increases significantly, beginning in the first trimester & reaching 20-40% above baseline at term. Alveolar ventilation increases by 50-70%. The increase in ventilation occurs because of increased metabolic CO2 production & because of increased respiratory drive due to the high serum progesterone level. The VT increases by 30-35%. The respiratory rate remains relatively constant or increases slightly.

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Arterial Blood Gases : Physiological hyperventilation results in respiratory alkalosis with compensatory renal excretion of bicarbonate. The arterial CO2 pressure reaches a plasma level of 28-32 mmHg & bicarbonate is ↓ to 18-21 mmol/L , maintaining an arterial pH in the range of 7.40-7.47. Mild hypoxemia might occur when the patient is in the supine position.

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Arterial Blood Gases : Oxygen consumption ↑ at the beginning of the first trimester & ↑ by 20-33% by term because of fetal demands & ↑ maternal metabolic processes. In active labor, hyperventilation ↑ & tachypnea caused by pain & anxiety might result in marked hypocapnia & respiratory alkalosis , adversely affecting fetal oxygenation by reducing uterine blood flow. In some patients, severe pain & anxiety can lead to rapid shallow breathing with alveolar hypoventilation , atelectasis , & mild hypoxemia.

Alterations In Normal Physiology During Pregnancy : 

Alterations In Normal Physiology During Pregnancy

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Hemodynamic Changes : Changes begin in the 1 st trimester of pregnancy & continue into the postpartum period. Maternal blood volume ↑ progressively, peaking at a value of approximately 40% above baseline by the 3 rd trimester. Plasma volume ↑ by 45-50% , & red cell mass ↑ by 20-30% , resulting in anemia of pregnancy. The ↑ blood volume is associated with ↑ cardiac output by 30-50% above baseline levels by 25 wks.

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Hemodynamic Changes : The heart rate ↑ & reaches a maximal value of 10-30% above baseline values by 32 wks. Systemic blood pressure ↓ slightly during pregnancy, with the diastolic pressure falling approximately 10-20% & reaching a nadir at 28 wks. Plasma colloid oncotic pressure ↓ because of the dilution of plasma proteins; the critical pulmonary capillary pressure at which pulmonary edema forms also ↓ . SVR & PVR ↓ by 20-30%.

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Dyspnea During Pregnancy : Dyspnea during pregnancy is quite common, occurring in approximately 60% of women with exertion & < 20% at rest. Physiologic dyspnea can occur early in pregnancy & does not interfere with daily activities. Although mechanical impediment by the gravid uterus is often blamed, hyperventilation due to ↑ progesterone levels is the most important mechanism.

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Dyspnea During Pregnancy : Distinguishing physiologic dyspnea from breathlessness caused by disorders complicating pregnancy or diseases that might coexist with pregnancy is essential. Actual exercise tolerance despite dyspnea is not greatly affected. The presence of other symptoms & signs of cardiopulmonary disease indicates a possible pathologic nature of dyspnea, & the patient should be evaluated.

Pulmonary Pharmacology During Pregnancy: 

Pulmonary Pharmacology During Pregnancy

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Absorption During Pregnancy : Both the rate of gastric emptying & the rate of gastric motility are decreased in the gravid patient. Thus, absorption properties are usually altered. The decreased intestinal motility can favor increased absorption. First-pass metabolism by the portal circulation is unchanged in pregnancy.

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Distribution During Pregnancy : The distribution of a drug is affected by the rate of perfusion of blood to the individual organs , lipid solubility , & the degree of binding to the proteins or tissue receptors. Because the physiologic volume of distribution is larger in pregnancy, high loading doses of the drug might be needed.

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Protein Binding During Pregnancy : During pregnancy, plasma protein binding usually decreases. This can cause higher circulating levels of free drug when normally protein-bound medication is administered.

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Elimination During Pregnancy : The clearance of drugs via direct extraction by the liver is not altered ; however, pregnancy can increase the hepatic metabolism of certain drugs, resulting in a decrease in plasma concentration. Because the glomerular filtration rate increases during gestation, drugs primarily eliminated by renal excretion are cleared more rapidly during pregnancy.

Pulmonary Medications During Pregnancy: 

Pulmonary Medications During Pregnancy

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Drugs & Pregnancy: Category (A) Drugs which have been taken by a large number of pregnant women & women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed. Category (B) Drugs that have been taken by only a limited number of pregnant women & women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Category (C) Drugs that, owing to their pharmacological effects, have caused, or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Category (D) Drugs that have caused, are suspected to have caused, or may be expected to cause an increased incidence of human fetal malformations, or irreversible damage. These drugs may also have adverse pharmacological effects. Category (X) Drugs that have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy, or when there is a possibility of pregnancy

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Methylxanthines During Pregnancy : Both theophylline & aminophylline readily cross the placenta , but no fetal ill effects or malformations have been reported. Theophylline pharmacokinetics are unaffected by pregnancy, and this drug is also secreted in breast milk.

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Beta Agonists During Pregnancy : β -agonists have little systemic absorption & a more potent bronchodilatory effect via inhalation. Data on the use of inhaled β -agonists showed no difference in perinatal mortality , congenital malformations , birth weight , or Apgar scores.

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Anticholinergics during Pregnancy : The use of anticholinergics proved to be safe during pregnancy & have been associated with no adverse fetal outcomes.

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Bronchodilators In Pregnancy : Generic Name Safety Category Theophyllines C Salmeterol C Ipratropium B Tiotropium No data available Terbutalin B Formoterol C Montelukast B

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Corticosteriods During Pregnancy : The use of corticosteroids during pregnancy continues to be controversial, although numerous reports confirm their use without adverse fetal effects. In 3 reports on human pregnancies, no congenital malformations or adverse fetal effects were found from ICS. Prednisone has been used extensively during pregnancy for a variety of conditions. It is associated with an increased incidence of cleft palates in animals but not in humans.

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Corticosteroids In Pregnancy : Generic Name Safety Category Budesonide B Fluticasone C Beclomethasone C Hydrocortisone C Prednisolone C Dexamethasone C Betamethasone C

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Antibiotics in Respiratory Infections : The major antibiotics considered safe during pregnancy are penicillin , cephalosporins , & erythromycin. Although penicillin & ampicillin readily cross the placenta, no adverse effects to the fetus are reported. Cephalosporins traverse the placenta to a moderate degree, but no adverse fetal effects occur. Erythromycin crosses the placenta to a low degree but achieves high levels in breast milk. The estolate formulation is contraindicated due to potential maternal hepatic toxicity. Antibiotics that have relative contraindications include sulfonamides , trimethoprim , aminoglycosides , nitrofurantoin , tetracyclines , & quinolones .

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Teratogens used in Pulmonary Diseases : These drugs include iodine-containing compounds . Brompheniramine , antihistamine , & coumarin cause various teratogenic effects. Ciprofloxacin , sulfonamides , tetracyclines , chloramphenicol , streptomycin , & rifampin have been associated with various effects.

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Antibiotics In Pregnancy : Generic Name Safety Category Penicillin B Cephalosporins B Imipenem/cilastatin C Meropenem B Aztreonam B Metronidazole B Clindamycin B Clarithromycin C Erythromycin/Azithromycin B Tetracyclines D Sulfonamides/Trimethoprim C Quinolones C Vancomycin C Chloramphenicol C

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Antihistaminic In Pregnancy : Generic Name Safety Category Chlorpheniramine B Loratadine B Ebastine Not established Desloratadine Not established Cetrizine Not established

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Cough Preparations In Pregnancy : Generic Name Safety Category Bromhexine Not established Acetylcysteine B Ambroxol Not established

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Teratogens used in Pulmonary Diseases : Ionizing radiation exposure to the fetus is associated with growth retardation , CNS effects , microcephaly , & eye malformations. Maternal radiation exposure of <0.05Gy is associated with no adverse effects, a dose of 0.05-0.1Gy is considered the gray zone & exposure to >0.1Gy is associated with significant fetal effects. Fetal ionizing radiation might cause ↑ in childhood leukemia. A CXR results in 0.002Gy exposure; perfusion lung scan 0.002Gy ; ventilation lung scan 0.004Gy ; pulmonary angiography 0.004Gy & venography 0.004Gy.

Pregnancy-Specific Pulmonary Disorders: 

Pregnancy-Specific Pulmonary Disorders

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Amniotic Fluid Embolism: Amniotic fluid embolism is a rare (1 per 8000-80,000) but potentially catastrophic complication, with a mortality rate of 10-80%. This usually occurs with labor & delivery but can be associated with uterine manipulation, uterine trauma, & the early postpartum period. Amniotic fluid containing particulate cellular elements enters the vascular circulation through endocervical veins or uterine tears , obstructs the pulmonary vessels, & causes vascular spasms, resulting in pulmonary hypertension. Acute left ventricular failure might occur, probably due to humoral events mediated by cytokines.

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Tocolytic Pulmonary Edema: β -adrenergic agonists, particularly terbutaline , are used to inhibit uterine contractions & preterm labor. These might cause pulmonary edema during pregnancy. The frequency varies from 0.3-9%. Mechanisms include prolonged exposure to catecholamines (which causes myocardial dysfunction), increased capillary permeability , & a large volume of intravenous fluid that may have been administered in response to maternal tachycardia. Glucocorticoids administered in preterm labor can also contribute to fluid retention.

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Gestation Trophoblastic Disease: Pulmonary hypertension & pulmonary edema can complicate benign hydatidiform pregnancy due to trophoblastic pulmonary embolism. This commonly occurs during evacuation of the uterus , & the incidence of pulmonary complications is higher in later gestations. Molar pregnancy can be associated with choriocarcinoma , which commonly produces multiple discrete pulmonary metastases & occasional pleural effusions.

Asthma & Pregnancy: 

Asthma & Pregnancy

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Asthma in Pregnancy: Asthma is one of the most common coexisting medical conditions affecting reproductive-aged woman. The course of asthma during pregnancy is variable; one third of patients improve , one third remain stable , & one third worsen. In patients with symptomatic asthma, gestational weeks 24-36 tend to be the most difficult.

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Asthma in Pregnancy: Only 10% of women experience asthma exacerbation during labor & delivery , and the severity tends to revert to that of pregnancy by 3 months' postpartum. Asthma is generally expected to follow a similar course during successive pregnancies. Infant outcome might be worse as asthma severity increases & that outcome with aggressive asthma management is usually good.

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Asthma in Pregnancy: Asthma exacerbations occur primarily in the late second trimester & are either triggered by viral infection or non-adherence to ICS. Severe exacerbations during pregnancy are a significant risk factor for a low birth weight baby and ICS use may reduce the risk. Clinical features of asthma during pregnancy are the same as those in the non-pregnant patient.

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Fetal Outcome in Asthma with Pregnancy: Asthma can have a number of deleterious effects on pregnancy outcome. An increased incidence of preterm births , low birth weight , & increased prenatal mortality largely related to poor asthma control has been reported.

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Acute Asthma Exacerbation with Pregnancy: Acute exacerbations that necessitate emergency department visits typically require a course of systemic corticosteroids. Oxygen should be used liberally, & the oxygen saturation should be maintained ≥ 95% to ensure fetal well-being. A beta-agonist with or without ipratropium should be given via MDI with a spacer or in nebulized form. Theophylline has limited use in acute exacerbations.

Venous Thromboembolic Disease & Pregnancy: 

Venous Thromboembolic Disease & Pregnancy

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The incidence of venous thromboembolism is estimated at 0.76-1.72/1000 pregnancies , which is four times as great as the risk in the non-pregnant population. Current estimates of deaths from pulmonary embolism are 1.1-1.5/100,000 deliveries in the US & Europe. Delayed diagnosis , delayed or inadequate treatment , & inadequate thromboprophylaxis account for many of the deaths due to venous thromboembolism Venous Thromboembilic Disease & Pregnancy:

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Diagnostic Algorithm for VTD in Pregnancy:

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Venous Thromboembilic Disease & Pregnancy:

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Venous Thromboembilic Disease & Pregnancy:

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Venous Thromboembilic Disease & Pregnancy:

ARDS & Pregnancy: 

ARDS & Pregnancy

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Pregnant patients are at risk of developing ARDS from obstetric complications & from non-obstetric conditions. Obstetric complications, such as amniotic fluid embolism , chorioamnionitis , trophoblastic embolism , & placental abruption , can produce acute lung injury. Pregnancy predisposes the patient to other pulmonary insults that can cause ARDS, such as gastric aspiration , pneumonia , air embolism , & massive hemorrhage. ARDS & Pregnancy:

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An association between pyelonephritis & the development of ARDS has been described in pregnancy. The mechanism is unclear , but iatrogenic factors, such as excessive fluid administration & tocolytic therapy , might be responsible. The reduced albumin level & resultant reduced plasma oncotic pressure occurring in pregnancy lowers the critical pulmonary capillary pressure at which pulmonary edema develops. ARDS & Pregnancy:

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No major differences exist in the management of pregnant & non-pregnant patient with ARDS. Fetal risk must be considered when pharmacological therapy is administered. Adequate maternal oxygen saturation is essential for fetal well-being. Excessive alkalosis can have adverse effects on placental perfusion , while maternal acidosis appears to be reasonably well tolerated by the fetus. Survival appears similar to ARDS in the general population. ARDS & Pregnancy:

Tuberculosis & Pregnancy: 

Tuberculosis & Pregnancy

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Untreated TB represents a far greater hazard to a pregnant woman & her fetus than does treatment of the disease. Infants born to women with untreated TB may be of lower birth weight than those born to women without TB &, rarely , the infant may acquire congenital TB. Thus, treatment of a pregnant woman with suspected TB should be started if the probability of TB is moderate to high. Administration of antituberculosis drugs is not an indication for termination of pregnancy. Tuberculosis & Pregnancy:

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HIV infection & drug-resistant TB present special challenges in pregnancy. Knowledge of drug interactions & teratogenic effects of antiretrovirals & 2 nd line antituberculosis agents is needed to treat these patients properly. TB in pregnancy is treated with isoniazid & rifampin & ethambutol . These drugs may cross the placental barrier, but they are associated with a low risk of adverse fetal effects. Streptomycin & other injectable antituberculous drugs are contraindicated because of fetal toxicity & potential teratogenic effects. Tuberculosis & Pregnancy:

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Isoniazid (Pregnancy Category A ) may cause cutaneous hypersensitivity , hepatitis , peripheral neuropathy. The risk of INH-induced hepatitis may be 2.5 times higher in pre-natal patients than the general population. Pyridoxine 25 mg/day , should be given to pregnant women receiving INH. INH given for treatment of latent TB (chemoprophylaxis) is considered safe & is recommended especially where the risk of developing disease is higher, e.g., with HIV co-infection or with a history of recent contact. Tuberculosis & Pregnancy:

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Rifampicin (Pregnancy Category C ) causes bleeding due to hypoprothrominaemia in infants & mothers especially if adminsterated in late pregnancy. Vitamin K is given to both the mother & the infant postpartum if rifampicin is used in the last few weeks of pregnancy. Rifampicin may cause nausea , vomiting & hepatitis. Tuberculosis & Pregnancy:

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Ethambutol (Pregnancy Category A ) is recommended for use in pregnancy. Retrobulbar neuritis occurs in <1% of cases on a daily dose of 15 mg /kg of Ethambutol. Tuberculosis & Pregnancy:

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There are no reports of fetal malformations attributable to pyrazinamide. The absence of such safety data is the reason that the CDC guidelines do not endorse pyrazinamide in pregnancy. Pyrazinamide may produce gastrointestinal upsets , arthralgia , hyperuricemia & hepatitis. If PZA is not included in the initial treatment regimen, the minimum duration of therapy is 9 months. Tuberculosis & Pregnancy:

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Streptomycin may commonly cause vertigo in mother apart from ototoxicity & nephrotoxicity , related to serum concentration & total dose of administered drug. Thus it is not recommended during pregnancy. Tuberculosis & Pregnancy:

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Breastfeeding should not be discouraged for women being treated with first-line agents , because the small concentrations of these drugs in breast milk do not produce toxic effects in the nursing infant. Conversely, drugs in breast milk should not be considered to serve as effective treatment for active TB or latent TB infection in a nursing infant. Tuberculosis & Breast Feeding:

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The use of Isoniazid , Rifampicin , Ethambutol , & Pyrazinamide , has been considered safe for breast feeding , but safety of PAS & injectable forms is unproven. Supplementary pyridoxine is recommended for the nursing mother receiving INH. The administration of the fluoroquinolones during breastfeeding is not recommended. The effect of these drugs gets minimized, if the mother breast feeds before taking the drugs & substitutes the next feed with formula preparation. Tuberculosis & Breast Feeding:

Obstructive Sleep Apnea & Pregnancy: 

Obstructive Sleep Apnea & Pregnancy

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High circulating level of progesterone during pregnancy ↑ ventilatory drive , which has a potentially protective effect. Obesity predisposes to SRBD & weight gain & ↑ nasal obstruction during pregnancy contributory to SDB. The enlarging uterus alters diaphragmatic function , thus resulting in ↓ FRC & causing shunting & hypoxemia leading to hypoxemia during hypoventilation in sleep. Pregnancy may precipitate or worsen sleep apnea. OSAS & Pregnancy:

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Pregnancy, if complicated by OSA , is associated with potential adverse effects for both the mother & the fetus. In general, apnea & hypopnea are uncommon in pregnancy because of the respiratory stimulatory effect of progesterone. Nocturnal hypoxemia adversely affects the fetus & poor fetal growth occurs in patients with this condition. nCPAP is a safe & effective treatment of SDB during pregnancy. OSAS & Pregnancy:

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