Severe Acute Asthma 329 Early studies evaluating the impact of asthma on pregnancy outcome showed signifi cant adverse effect. The majority of these papers were retrospective, and were based on birth certifi cate data [32,33] . Patients were classifi ed according to the presence or absence of the diagnostic code for asthma and not on the severity of the asthma. These studies showed an increased risk of preterm birth, low birth weight, pregnancy - induced hypertension, pre- eclampsia, hemorrhage, perinatal mortality and congenital mal- formations in patients with asthma [2,27,32,34,35] . The fi ndings were supported by Liu et al [36] . in a retrospective cohort study which employed an administrative database with over 2000 asthma patients and 8000 controls. These authors also found an increased risk of preterm labor, pregnancy - induced hyperten- sion, small for gestational age, abruption, chorioamniotis, and cesarean delivery in patients with asthma [36] . Demissie et al. [33] in their case – control study, controlled for confounding factors such as age, education, parity, race, diabetes, hyperten- sion, cigarette use, alcohol and drug use. They also showed an increase in the risk of preterm birth, small for gestation, pregnancy - induced hypertension, previa, congenital anomalies, and cesarean delivery in patients with asthma [33] . While these studies all demonstrated increased risk of perinatal compli- cations in patients with asthma, none controlled for the severity of asthma or possible impact of the medications used as treatment. More recently, several studies have been specifi cally designed to address the impact of asthma severity and medication use on pregnancy outcome. In Kallen ’ s population study [37] , patients were subdivided into those without asthma, those with asthma of any severity, and those with severe asthma. Patients with asthma Effect of p regnancy on a sthma The classic statement in regards to the impact of pregnancy on asthma is the one - third rule: one - third improve, one - third worsen, and one - third remain unchanged. This generality is sup- ported by several recent studies [25,1] . Dombrowski et al. have the most detailed information in their recent prospective study where the asthma group was subdivided by severity [1] . They found that in general 23% improved, 30.3% worsened and 46.7% remained unchanged [1] . It was also noted that as severity increased so did the rate of exacerbation and need for hospitaliza- tion [1] (Table 23.3 ). Exacerbations are most frequent from 17 – 24 weeks, and appear to be less severe during the last 4 weeks of pregnancy [26 – 31] . Effect of a sthma on p regnancy The effect of asthma on pregnancy is an area of ongoing debate with some studies showing little to no impact, and others sug- gesting signifi cant risk. –2000 –1000 0 1000 2000 3000 4000 Non- pregnancy Late pregnancy Inspiratory reserve Tidal volume Expiratory reserve Residual volume Inspiratory capacity Functional residual capacity Vital capacity mL Figure 23.1 Lung volumes. Table 23.3 Exacerbation and hospitalization rates in pregnancy based upon severity in a large prospective observation cohort study. * Mild asthma Moderate asthma Severe asthma Asthma exacerbation rate (%) 12.6 25.7 51.9 Asthma hospitalization rate (%) 2.3 6.8 26.9 * From Dombrowski MP et al. [1] . Chapter 23 330 in the uterus, airways, and vasculature [48] . While asthma may be associated with signifi cant risk in some (but not all) cases, it does appear that close observation and aggressive management of moderate to severe asthma can result in improved pregnancy outcome. Management Prepregnancy As asthma severity and degree of control clearly impact preg- nancy outcome, the optimization of care prior to pregnancy is of great importance. In this regard, given the importance of home monitoring in the management of these cases, review of the appropriate operation of a peak fl ow meter and the recording of peak expiratory fl ow rates will be of benefi t to the patient. This information should be evaluated regularly and therapy optimized prior to conception. Patients need to be educated on the impor- tance of continuing all medications once pregnancy is achieved to avoid exacerbation of their asthma. Pregnancy As discussed above, it is important to maintain tight asthma control to decrease the risk of pregnancy complications. To this end, some discussion of the patient ’ s asthma control should be documented at each prenatal visit. It is important to educate the pregnant patient at the fi rst visit that well controlled asth- matics have little increased risk, yet poor control may signifi - cantly increase risk to both mother and fetus [49] . Hence, more critical evaluation of symptoms and reliable objective measure- ment of pulmonary function by PEFR assessment are vital. As PEFR does not change in pregnancy (typically 380 – 550 L/min), it can continue to be used to monitor lung function, and to separate asthma - associated dyspnea from pregnancy - associated dyspnea (which does not alter the PEFR). Patients should be asked to perform twice daily (on awakening and at midday) PEFR measurements and record these values for review at each prenatal visit. During these visits, it is recommended that pro- viders verify proper peak fl ow meter and inhaler use, as well as review asthma management plans with a fl exible approach to making adjustments when necessary. Due to the risk of growth restriction, especially in those requiring oral steroids, routine ultrasound should be performed, and antenatal testing should be considered at all levels of severity, but especially in those with severe asthma or recent exacerbation. The NAEEP Working group on Asthma in Pregnancy emphasizes the following fi ve aspects of care: 1 objective evaluation of maternal/fetal condition 2 avoidance/control of triggers such as smoke, dust and pollutants 3 pharmacological treatment 4 educational support, especially with regard to early recognition of symptoms 5 psychological support. of any severity showed an increase in risk of 15 – 20% for pre - eclampsia, preterm delivery and low birth weight. This risk was higher (30 – 100% increase) in those with severe disease [37] (Table 23.4 ). This study is limited by its retrospective nature and the impact of medication use was not addressed. Perlow et al. [38] addressed the impact of steroid use in a retrospective case – con- trol study. Patients with asthma were subdivided based upon the use of long - term steroids. All patients with asthma were found to have an increased risk of cesarean delivery for fetal distress, and for preterm delivery < 37 weeks when compared with controls [38] . Among oral steroid - dependent asthmatics, there was a sig- nifi cant increase in the risk of gestational diabetes and low birth weight [38] . Dombrowski et al. published a prospective observa- tional cohort study in 2004 in which they used the NAEEP Working group on Asthma in Pregnancy defi nitions for mild, moderate and severe asthma. Over 800 patients were included in each of the groups (control, mild, and moderate to severe asthma) and the patients were followed through pregnancy with monthly visits. No difference was found in antepartum, delivery, or post- partum outcomes including preterm delivery less than 32 or less than 37 weeks in patients with any form of asthma [1] . There was an increase in cesarean delivery in patients with moderate to severe asthma [1] . When only severe asthmatics were evaluated, an increased risk of gestational diabetes and preterm delivery prior to 37 weeks was found. However, the study was not designed to control for steroid use [1] . Thus, despite multiple studies and a tremendous amount of published information, there continues to be controversy regard- ing the extent of the impact of asthma on pregnancy. There are data suggesting that asthma can be associated with increased risk of pre - eclampsia, pregnancy induced hypertension and preterm birth [27] . and asthma severity has clearly been shown to have an impact on the complication risk in pregnancy [28,30,33,34,38 – 41] . However, in those studies where asthma was prospectively managed and controlled, such risks were minimized [4,39,41 – 47] . It remains unclear as to whether these risks are the result of maternal hypoxia and hypocapnia secondary to medication use, or whether they are the result of a fundamental abnormality of smooth muscle in asthmatics which manifests as increased tone Table 23.4 Odds ration (95% CI ) for pregnancy outcomes in patients with asthma versus control in a large population - based study. * Outcome All subjects with asthma (n = 36 985) Severe asthma (n = 1396) Perinatal mortality 1.21 (1.08 – 1.35) 1.28 (0.76 – 2.17) Pre - eclampsia 1.15 (1.08 – 1.23) 1.42 (1.09 – 1.86) Preterm birth ( < 37 weeks) 1.15 (1.09 – 1.21) 1.56 (1.27 – 1.90) Low birth weight ( < 2500 g) 1.21 (1.14 – 1.29) 1.98 (1.52 – 2.59) Congenital malformations 1.05 (0.99 – 1.10) 1.08 (0.83 – 1.4) * From Kallen B, Rydhstroem H, Aberg A [37] . Severe Acute Asthma 331 linergic, is known to cause signifi cant fetal tachycardia when used systemically and is therefore not recommended [59,60] . Maintenance Methylxanthines The most commonly used methylxanthine in pregnant women is theophylline, which is traditionally employed as an add - on therapy to inhaled steroids in patients with moderate persistent asthma [39] . A number of studies have confi rmed that this agent is not associated with an increased risk of congenital malforma- tions or poor perinatal outcomes [34,39] . However, theophylline has a narrow range between the therapeutic and toxic concentra- tions and use of this drug requires close monitoring of serum levels. This situation is made more compelling in pregnancy due to the decreased albumin binding noted in pregnant women and this increases the proportion of free drug in the circulation. With more drug available for metabolism, the total level (free plus bound) falls [61] . To complicate matters more, the clearance of theophylline is reduced by 20% in the third trimester [34,39,62] . Taking the physiologic changes of pregnancy into account, it is recommended that target levels be adjusted in pregnant women to 8 – 12 mcg/mL instead of the 10 – 15 used outside of pregnancy [61] . Monitoring of maternal blood levels is not only important for the mother ’ s health, but is similarly important for fetal health. Theophylline crosses the placenta and leads to fetal tachycardia, as well as neonatal irritability, jitteriness, and vomiting if the level is elevated [63,64] . Cromolyn s odium Cromolyn sodium is a mast cell stabilizer/inhaled non - steroidal agent. It blocks both early - and late - phase pulmonary responses to an allergen challenge, and also prevents the development of airway hyperresponsiveness [65] . It is effective when taken prior to exposure but does not relieve symptoms once they have occurred [39] . Cromolyn sodium is effective in mild intermittent asthma in combination with short - acting β - agonists [54] . There is no increased risk of fetal malformation or poor pregnancy outcome, and this drug should be continued during pregnancy if it has been shown to be effective outside of pregnancy [34,39] . However, since it is not as effective as steroid therapy, cromolyn sodium should not be a fi rst - line agent for managing asthma in pregnancy [34] . Inhaled c orticosteroids Inhaled corticosteroids are considered the mainstay of treatment for persistent asthma [34,54] . Budesonide (Pulmicort ® ) and beclomethasone (Qvar ® ) are the two agents with the most data available regarding use during pregnancy [34,60] . Studies have shown that the use of these inhaled steroids in standard doses is not associated with malformations, fetal growth restriction, still- birth, or fetal mortality [34,39] . However when used in high doses, greater than 1000 – 1500 mcg/day, systemic effects such as increased intraocular pressure, cataracts, bone loss, growth restriction, and hypothalamic – pituitary – adrenal (HPA) suppres- Medications Prior to discussing therapy recommendations, it may be useful to review the potential impact of asthma medications on pregnancy. In general, it is recommended that patients remain on the same drugs and dosages that are used outside of preg- nancy. Inhaled agents are preferred over oral agents to reduce systemic effects and minimize any possible fetal effects [32,50,51] . Medications for asthma are divided into two types: (i) rescue (those used to treat acute bronchospasm and give symptomatic relief without treating the underlying cause of the bronchospasm) and (ii) maintenance (those that help control airway hyperreac- tivity and treat the underlying infl ammation). Rescue m edications Short - acting β - agonists These drugs are key to asthma management. Short - acting β - agonists include metaproteronol (Alupent ® ), terbutaline (Brethine ® ), and albuterol (Ventolin ® , Proventil ® ). These inhala- tion agents are good for acute and mild intermittent asthma, as they have a rapid onset resulting in maximum bronchodilation with minimal side effects [52,53] . Side effects of these drugs include tremulousness, palpitations and/or anxiety. However, such side effects can be minimized by the use of a spacer and mouth rinsing after inhalation [54] . Studies have shown no asso- ciation between short - acting β - agonist use and increased risk of congenital malformations or adverse pregnancy outcome [34,55,56] . Long - acting β – agonists While much has been published on the short - acting β - agonists, less is known with regard to long - acting β - agonists. These agents include salmeterol (Serevent discus ® ) and formoterol (Foradil ® ). Long - acting β - agonists are commonly used as add - on therapy for those not controlled with inhaled steroids [39] . There are cur- rently few data addressing safety in humans, and animal studies have not been particularly reasurring [39] . Of the two drugs, salmeterol appears more promising than formoterol [39] . Currently, consensus recommendations support the use of long - acting β - agonists in patients with moderate to severe asthma who demonstrate a good response to these agents in their prepreg- nancy state, or as an add - on therapy in patients already using inhaled steroids and who need additional therapy [39] . Anticholinergics The main anticholinergic drug used in asthma therapy is ipratro- pium (Atrovent ® ) which, in its nebulized form, has shown syn- ergistic bronchodilator effect when added to inhaled β - agonists [57,58] . Despite the facts that both animal and human studies have shown negligible adverse effects on the fetus, and that these drugs are felt to be safe, they are not being used widely [59,60] . Anticholinergic use may be appropriate as additional therapy in cases of acute asthma that do not improve signifi cantly after an initial β - agonist treatment [39] . Atropine, a well known anticho- Chapter 23 332 gested a teratologic effect, but zafi rlukast showed no teratogenic- ity at oral doses 160 times greater than the maximum human dose [39,60] . Current ACOG guidelines suggest that any leukotriene modifi er except zileuton can be used in pregnant patients who require this class of drug because of resistance to other medica- tions [34] . Combination d rugs These include Advair Discus ® and Combivent ® . Advair ® is a com- bination of salmeterol, a long - acting β - agonist, and fl uticasone, an inhaled steroid. Combivent ® is composed of albuterol, a short - acting β - agonist, and ipratropium, an anticholinergic agent. The individual drugs have been discussed in detail above. Current recommendations are for these medications to be continued in patients who are well controlled on them. However, since each combination medication contains at least one component for which few pregnancy data are available, such drugs should only be initiated in pregnancy if benefi ts outweigh the risk. Immunotherapy Allergen immunotherapy can be helpful in those patients whose specifi c allergy triggers are known, and whose symptoms persist despite optimal avoidance of triggers, and appropriate drug therapy. While there has never been a direct association seen between immunotherapy and poor pregnancy outcome, the risk of a systemic reaction with fi rst - time exposure remains a signifi - cant risk [76] . Thus, for those who began therapy prior to preg- nancy, who clearly benefi t from such treatment, and who have no reaction on a maintenance dose, most authorities would support continuance of the therapy [59,76] . Some authors have recommended that doses should be signifi cantly reduced to avoid a systemic reaction, but this advice is not uniformly supported [77] . It is not currently recommended for patients to initiate immunotherapy during pregnancy because of the above - men- tioned potential for systemic reaction [78] . Other m edications The infl uenza vaccination is recommended for all pregnant patients and especially so in those with respiratory disease. All patients who will be pregnant between October through May should received the inactivated injectable infl uenza vaccine. The intranasal form is a live virus form and therefore should not be administered in pregnancy [14] . Allergic rhinitis is a common upper respiratory disorder and can induce an asthma exacerbation. Intranasal steroids such as loratadine (Claritin ® ) and cetirizine (Zyrtec ® ) are effective treat- ment for this and have no known impact on pregnancy. While decongestant use is common in pregnancy secondary to nasal hyperemia, inhaled decongestants and steroids are recommended over the oral forms of decongestant since the latter have been associated with gastroschisis when used in the fi rst trimester [74] . Pregnancy - induced hypertension is commonly seen in preg- nancy and the incidence appears to be slightly increased in patients with asthma. In many cases the drug of choice for treat- sion have been reported [54] . Other medications in this group, including triamcinolone (Azmacort ® ), glunisolide, or fl uticasone (Flovent ® ), are less well studied regarding safety of use in preg- nancy. Despite this, most agree that it is not unreasonable to continue their use in patients who are well controlled on the medication prior to becoming pregnant [34,39] . Regardless of the medication used, oral candidiasis (thrush) is a recognized side effect which can be signifi cantly decreased by oral rinsing after inhalation or by using a spacer which maximizes the delivery to the bronchi while minimizing oropharyngeal deposition. Systemic c orticosteroids In contrast to the low incidence of risk with inhaled corticoste- roids, systemic corticosteroid use is associated with defi nite pregnancy complications. Studies have consistently shown that systemic steroids increases the risk of low birth weight, preterm delivery, pregnancy - induced hypertension, pre - eclampsia, and gestational diabetes [31,37 – 39,56,66 – 71] . Some, but not all, studies have reported an association with antepartum and post- partum hemorrhage, and an increased rate of infection [31,34] . One of the most controversial fi ndings is that of the impact of systemic steroid use on the rate of fetal malformation. Early studies found a signifi cantly increased risk of cleft lip and palate when these drugs were taken during pregnancy [69] . However, this study did not classify the outcomes according to the trimester of exposure. In large case control trials stratifi ed by trimester of exposure, a 0.2 – 0.3 - fold increase (20 – 30%) risk of oral clefting was seen in patients who had experienced fi rst - trimester exposure [39,69,72,73] . This was not confi rmed however in a large case control trial [74] in which exposure was stratifi ed by gestational month of exposure. In this study, there was no association with increased risk when steroids were taken during the second and third months of pregnancy [74] . Despite the potential for a small increase in fetal risk, it has been the recommendation of at least two working groups (ACOG and NAEPP) that if oral steroids are needed to control severe asthma, the benefi ts of using these medi- cations during pregnancy may outweigh the risks. The same two Working Groups also recommend the use of oral steroids for long - term management of patients with severe asthma and in those women with severe asthma who experience exacerbations during pregnancy [14,39] . Leukotriene m odifi ers Leukotrienes are potent chemical mediators of the allergic response in asthma. They stimulate bronchoconstriction and mucus hypersecretion, and promote microvascular leakage, edema formation, and eosinophil chemoattraction. Medications which modify and diminish the effects of leukotrienes have been found to allow better asthma control. This class of drugs (leaukotriene modifi ers) includes zileuton (Zylfo ® ), zafi rlukast (Accolade ® ), and montelukast (Singulair ® ). While few data are available regarding their use in pregnancy, the Human Merck Registry has not shown any increased risk of malformation [39,75] . There are animal studies on zileuton which have sug- Severe Acute Asthma 333 Table 23.5 Asthma treatment in pregnancy. ± Asthma severity Recommended therapy * Alternative therapy Mild intermittent No daily therapy needed β 2 agonist for symptoms − Mild persistent Low - dose inhaled corticosteroid (budesonide preferred) Cromolyn Leukotriene receptor antagonist Theophylline Moderate persistent Either: Low - dose inhaled corticosteroid and long - acting inhaled β 2 agonist or Medium - dose inhaled corticosteroid with or without long - acting β 2 agonist Low - dose inhaled corticosteroid and theophylline or leukotriene receptor antagonist Severe persistent High - dose inhaled corticosteroid and long - acting inhaled β 2 agonist and oral steroid if needed High - dose inhaled corticosteroid and theophylline * Short - acting bronchodilator for all types: 2 – 4 puffs short - acting inhaled β 2 agonist as needed for symptoms q4 – 6 ° . ± From the National Institutes of Health [14] . ment is a β − blocker such as labetolol. While such a medication would ordinarily be contraindicated in patients with asthma, if this class of antihypertensive is deemed essential to control the hypertension, a risk/benefi t evaluation should be undertaken. Treatment Treatment plans are essential in the care of asthmatic patients. They allow for patients to become more involved in their own care and assist in the formation of an action plan for use in the event of an asthma attack. Treatment recommendations are given for each type of asthma in Table 23.5 . Initiation of care can either start at the level appropriate to the patient ’ s severity and move up if not controlled, or start at a level above that suggested by severity in order to gain rapid control of the attack and then move down when stable for several weeks [59] . Action plans are based on the best PEFR that a patient has ever obtained. A commonly used action plan for an acute asthma attack is shown in Figure 23.2 . Patients with acute asthma who present to the emergency department require expeditious evaluation and care. Initial care is no different than in non - pregnant patients and includes oxygen, nebulized β - agonists, nebulized anticholiniergic drugs such as ipratropium, as well as oral and/or intravenous steroids as needed. Fetal evaluation should be performed if the baby is beyond 23 – 24 weeks and in those at lesser gestational age confi rmation of heart beat should be documented. There should be a low threshold for admission, and guidelines for admission include a PEFR < 60% of their baseline, PO 2 < 70 mmHg at sea level, PCO 2 > 35 mmHg, heart rate > 120 bpm, or a respiratory rate > 22/min. It is impor- tant to remember that a PCO 2 > 40 mmHg in pregnancy suggests impending respiratory failure as normal levels are 27 – 32 mmHg, and thus such patients should be admitted to an ICU where immediate airway management and ventilation options are avail- able. For those who do not respond to initial β - agonist therapy, an oral steroid burst is indicated regardless of severity. This is done by administrating 40 – 60 mg of oral prednisone per day for 1 week followed by a taper over 7 – 14 days. Patients who require admission secondary to concern about potential respiratory failure(P a CO 2 > 40 or PEFR < 25% of pre- dicted) should be admitted to an intensive care unit and an inten- sivist should be consulted. When the fetus is beyond 23 – 24 weeks, continuous fetal heart rate monitoring is recommended. It is important to note that maternal hypercapnia could result in fetal respiratory acidosis and a shift in the fetal hemoglobin dissocia- tion curve to the right. This limits the ability of fetal hemoglobin to bind oxygen. Because of this, the NAEPP Working Group recommends that patients should be intubated and ventilated if any of the following criteria are fulfi lled: 1 Inability to maintain a P a O 2 > 60 mmHg with 90% saturation despite supplemental oxygen. 2 Inability to maintain a P a CO 2 < 40 mmHg. 3 Maternal exhaustion. 4 Worsening acidosis despite bronchodilator therapy (pH7.2 – 7.25). 5 Altered maternal consciousness. An approach to the care of a pregnant patient presenting to an emergency room for an acute asthma attack is shown in Figure 23.3 . Delivery Women with asthma do not require any alterations in the man- agement of labor or mode of delivery based simply on their affl ic- tion. However, additional care is needed in order to avoid specifi c complications that can occur at the time of delivery. These patients should continue the same inhalation therapy during labor as they have been taking in the preceeding weeks [78,79] . Only patients who used oral corticosteroids in the 4 weeks prior to delivery require additional rescue dose steroid therapy, because Chapter 23 334 Anesthesia consultation is recommended at the time of admis- sion for women with a history of moderate to severe asthma. Postpartum Following delivery, patients should continue their inhaled medi- cations in the same dosage and route as they previously used. Those on oral steroids may require intravenous dosing as described above until oral medications are tolerated. Breastfeeding is not contraindicated in the presence of any of the medications used for the treatment of asthma since only small amounts of these drugs enter the breast milk [85] . However, in patients who use theophylline, there is the possibility that sensitive neonates can experience vomiting, jitteriness, tachycardia, and feeding dif- fi culties, and the neonatologist should be aware of the maternal medication exposure history. Summary Patients with asthma can expect an uneventful pregnancy for the most part. It is important, however, for each patient to under- stand the impact of poorly controlled asthma on her pregnancy of potential hypothalamic – pituitary – adrenal axis (HPA) sup- pression. These patients should receive intravenous hydrocorti- sone (100 mg every 6 – 8 hours) during labor until either 24 hours after delivery or until oral medications are tolerated [80] . For labor induction and augmentation oxytocin and prostaglandin E 2 are safe [60,81] . While prostaglandin E 2 is a bronchodilator, pros- taglandin F 2 α is a bronchoconstrictor and therefore should not be used in these patients, even for severe postpartum hemorrhage unless the risk of death from bleeding outweighs the potential risk of precipitating a severe asthma attack [60,81 – 84] . Ergonovine and other ergots also cause bronchospasm and should also not be used if at all possible [81] . In the management of asthmatic patients with preterm labor, magnesium sulfate is safe (since it has bronchodilator effects). Indomethacin (Indocin ® ) can induce bronchospasm in aspirin - sensitive patients and therefore should be used with caution [10] . While pain management is strongly encouraged there are some drugs that should be avoided since they cause histamine release (morphine and meperidine). More appropriate alternatives include butorphanol and fentanyl [59,81] . For those who require general anesthesia, ketamine and halogenated anesthetics are preferred due to their bronchodila- tory effect [59,81] . Continue short-acting β 2 agonist every 3–4 hours for 14–48 hours For patients on inhaled steroid, double dose for 7–10 days Contact physician for follow-up Short-acting β 2 agonist Treatment 2 more times Repeat PEFR If PEFR persists 50–80% predicted +continued decreased fetal movement seek emergency care Repeat β 2 agonist and seek emergency care Good Response PEFR >80% predicted No wheezing or shortness of breath Normal fetal activity Incomplete Response PEFR 50–80% predicted Persistent wheezing Persistent shortness of breath Decreased fetal activity Initial Treatment 2–4 puffs by MDI of short-acting inhaled β 2 agonist Perform PEFR Poor Response PEFR <50% predicted Marked wheezing Shortness of breath Decreased fetal movement Figure 23.2 Home action plan in the management of acute asthma exacerbations. Reproduced from National Institutes of Health [14] . Severe Acute Asthma 335 2 Alexander S , Dodds L , Armson BA . Perinatal outcomes in women with asthma during pregnancy . Obstet Gynecol 1998 ; 92 : 435 – 440 . 3 Kwon HL , Belanger K , Bracken M . Asthma prevalence among preg- nant and childbearing - aged women in the United States: estimates from national health surveys . Ann Epidemiol 2003 ; 13 : 317 – 324 . 4 Schatz M , Zeiger RS , Hoffman CP . Intrauterine growth is related to gestational pulmonary function in pregnant asthmatic women. Kaiser - Permanente Asthma and Pregnancy Study Group . Chest 1990 ; 98 : 389 – 392 . 5 Fanta CH , Fletcher SW . Diagnosis of asthma . In: Rose BD , ed. UpToDate . Wellesley, MA : UpToDate , 2006 . 6 Global Initiative for Asthma Management and Prevention . NHLBI/ WHO Workshop Report. Bethesda, MD: US Department of Health and Human Services. National Institutes of Health, 1995 . 7 Weinberger SE , Schatz M . Physiology and clinical course of asthma in pregnancy . In: Rose BD , ed. UpToDate . Wellesley, MA : UpToDate , 2006 . (increased risk of complications including preterm birth, preg- nancy - induced hypertension, pre - eclampsia and growth restric- tion). To avoid such outcomes frequent prenatal visits with close attention to asthma symptoms are essential along with regular ultrasound evaluation of fetal growth. Patients should be encour- aged to closely monitor their symptoms by the routine use of peak expiratory fl ow measurements and to seek attention early if wors- ening symptoms do not respond to initial β - agonist treatment. Through this close observation and early intervention successful pregnancy outcomes are not only possible but routine. References 1 Dombrowski MP , Schatz M , Wise R , et al. Asthma during pregnancy . Obstet Gynecol 2004 ; 103 : 5 – 12 . Intubation and mechanical ventilation with 100% O 2 Nebulized short-acting inhaled β 2 agonist Inhaled ipratropium bromide Intravenous steroids FEV 1 or PEFR ≥70% Sustained 1 hour after last treatment No distress Normal PE Reasurring fetal status Continue short-acting β 2 agonist Continue course of oral steroid Step up baseline therapy until follow-up Short-acting β 2 agonist Ipratropium bromide Systemic steroid Oxygen Monitor PEFR/FEV 1 , O 2 sat Continue fetal assessment until stable History and physical PEFR Fetal assessment if viable Either BPP or continuous EFM Short-acting inhaled β 2 agonist up to three doses in first hour Oxygen to achieve O 2 sat ≥95% Oral steroid if no immediate response or recently taken by patient High-dose short-acting inhaled β 2 agonist every 20 minutes for 1 hour Inhaled ipratropium bromide Systemic steroid Oxygen to achieve O 2 sat>95% FEV 1 or PEFR ≥50% but <70% Mild or moderate symptoms Reassurring fetal status FEV 1 or PEFR <50% PCO 2 >42 mmHg Severe symptoms Initial Assessment FEV 1 or PEFR >50% FEV 1 or PEFR <50% Impending or Actual Respiratory Arrest Repeat Assessment Admit to ICU Incomplete Response Poor Response Good Response Discharge Home Individualize need for hospitalization Admit to Hospital Figure 23.3 Emergency room care of a pregnant patient with acute asthma. Reproduced from National Institutes of Health [14] . Chapter 23 336 30 Schatz M , Dombrowski MP , Wise R , et al. Asthma morbidity during pregnancy can be predicted by severity classifi cation . J Allergy Clin Immunol 2003 ; 112 : 283 . 31 Nelson - Piercy C . Asthma in pregnancy . Thorax 2001 ; 56 : 325 . 32 Bahna SL , Bjerkedal T . The course and outcome of pregnancy in women with bronchial asthma . Acta Allergol 1972 ; 27 : 397 – 406 . 33 Demissie K , Breckenridge MB , Rhoads GG . Infant and maternal out- comes in the pregnancies of asthmatic women . Am J Respir Crit Care Med 1998 ; 158 : 1091 – 1095 . 34 Tan KS , Thomson NC . Asthma in pregnancy . Am J Med 2000 ; 209 : 727 . 35 Schatz M , Dombrowski M . Outcomes of pregnancy in asthmatic women . Immunol Allergy Clin North Am 2000 ; 20 : 715 – 727 . 36 Liu S , Wen S , Demissie K , et al. Maternal asthma and pregnancy outcomes: a retrospective cohort study . Am J Obstet Gynecol 2001 ; 184 : 90 – 96 . 37 Kallen B , Rydhstroem H , Aberg A . Asthma during pregnancy – a population based study . Eur J Epidemiol 2000 ; 16 : 167 . 38 Perlow JH , Montgomery D , Morgan MA , et al. Severity of asthma and perinatal outcome . Am J Obstet Gynecol 1992 ; 167 : 963 – 967 . 39 Namazy JA , Schatz M . Update in the treatment of asthma during pregnancy . Clin Rev Allergy Immunol 2004 ; 26 : 139 – 148 . 40 Sorensen TK , Dempsey JC , Xiao R , et al. Maternal asthma and risk of preterm delivery . Ann Epidemiol 2003 ; 13 : 267 – 272 . 41 Greenberger PA , Patterson R . The outcome of pregnancy complicated by severe asthma . Allergy Proc 1988 ; 9 : 539 – 543 . 42 Schatz M . Interrelationships between asthma and pregnancy: a litera- ture review . J Allergy Clin Immunol 1999 ; 103 : S330 – 336 . 43 Jana N , Vasishta K , Saha SC , Khunnu B . Effect of bronchial asthma on the course of pregnancy,labour and perinatal outcome . J Obstet Gynaecol 1995 ; 3 : 227 – 232 . 44 Schatz M , Zeiger RS , Hoffman GP , et al. Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis . Am J Respir Crit Care Med 1995 ; 151 : 1170 – 1174 . 45 Stenius - Aarniala B , Piirila P , Teramo K . Asthma and pregnancy: a prospective study of 198 pregnancies . Thorax 1988 ; 43 : 12 – 18 . 46 Lao T , Huengsburg M . Labour and delivery in mothers with asthma . Eur J Obstet Gynecol Reprod Biol 1990 ; 35 : 183 – 190 . 47 Doucette JT , Bracken MB . Possible role of asthma in the risk of preterm labor and delivery . Epidemiology 1993 ; 2 : 143 – 150 . 48 Landau R , Xie HG , Dishy V , Stein CM . β 2 - Adrenergic receptor genotype and preterm delivery . Am J Obstet Gynecol 2002 ; 187 : 1294 . 49 National Asthma Education and Prevention Program: Expert Panel Report 2 . Guidelines for the Diagnosis and Management of Asthma . NIH Publication No. 97 - 4051 . Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, 1997 . 50 Clark SL . Asthma in pregnancy. National Asthma Education Program Working Group on Asthma and Pregnancy. National Institutes of Health, National Heart, Lung, and Blood Institute . Obstet Gynecol 1993 ; 82 : 1036 – 1040 . 51 Schatz M , Patterson R , Zeitz S . Corticosteroid therapy for the preg- nant asthmatic patient . JAMA 1975 ; 233 : 804 – 807 . 52 Shim C , Williams MH . Bronchial response to oral versus aerosol metaproterenol in asthma . Ann Intern Med 1981 ; 93 : 428 . 53 Shim C , Williams MH . Comparison of oral aminophylline and aerosol metaproterenol in asthma . Am J Med 1981 ; 71 : 452 . 54 Fanta CH , Fletcher SW . Overview of asthma management . In: Rose BD , ed. UpToDate . Wellesley, MA : UpToDate , 2006 . 8 Bailey WC , Manzella BA . Learn Asthma Control in Seven Days . Birmingham, AL : Board of Trustees of the University of Alabama , 1989 . 9 Harding SM . Recent clinical investigations examining the association of asthma and gastroesophageal refl ux . Am J Med 2003 ; 115 ( Suppl 3A ): 39S . 10 Dombrowski MP . Asthma and pregnancy . Obstet Gynecol 2006 ; 108 : 667 – 681 . 11 Enright PL , Lebowitz MD , Cockcroft DW . Physiologic measures: pul- monary function test . Am J Respir Crit Care Med 1994 ; 149 : S9 . 12 Irvin CG , Eidelman D . Airways mechanics in asthma . In: Holgate S , Busse W , eds. Rhinitis and Asthma . Boston : Blackwell Scientifi c Publications , 1995 . 13 Fergusson DM , Horwood LJ , Shannon FT . Parental asthma, parental eczema and asthma and eczema in early childhood . J Chronic Dis 1983 ; 36 : 517 . 14 National Institutes of Health, National Heart, Lung and Blood Institute, National Asthma Education and Prevention Program . Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment, Update 2004 . Available at: www.nhlbi.nih.gov?health/prof/lung/asthma/astpreg. htm . 15 Turner AF . The chest radiograph in pregnancy . Clin Obstet Gynecol 1975 ; 18 : 65 . 16 Thomson K , Cohen M . Studies on the circulation in normal preg- nancy: II. Vital capacity observations in normal pregnant women . Surg Gynecol Obstet 1938 ; 66 : 591 . 17 Gilroy RJ , Mangura BT , Lavietes MH . Rib cage and abdominal volume displacements during breathing in pregnancy . Am Rev Respir Dis 1988 ; 137 : 668 . 18 Toppozada H , Michaels L , Toppozada M , et al. The human respira- tory nasal mucosa in pregnancy. An electron microscopic and histo- chemical study . J Laryngol Otol 1982 ; 96 : 613 . 19 Bende M , Hallgarde M , Sjogren U , Uvnas - Moberg K . Nasal conges- tion during pregnancy . Clin Otolaryngol 1989 ; 14 : 385 . 20 Bonica J . Principles and Practice of Obstetric Analgesia and Anesthesia . Philadelphia : FA Davis , 1962 . 21 Bonica JJ . Maternal respiratory changes during pregnancy and partu- rition . Clin Anesth 1974 ; 10 : 1 . 22 Weinberger SE , Weiss ST , Cohen WR , et al. Pregnancy and the lung . Am Rev Respir Dis 1980 ; 121 : 559 . 23 Norregaard O , Schultz P , Ostergaard A , Dahl R . Lung function and postural changes during pregnancy . Respir Med 1989 ; 83 : 467 . 24 Stenius - Aarniala B . Pulmonary function during pregnancy in health and in asthma . In: Schatz M , Zeiger RS , eds. Asthma and Allergy in Pregnancy and Early Infancy . New York : Marcel Dekker , 1993 : 53 – 62 . 25 Gluck JC , Gluck PA . The effects of pregnancy on asthma: a prospec- tive study . Ann Allergy 1976 ; 37 : 164 – 168 . 26 Stenius - Aarniala B , Hedman J , Teramo K . Acute asthma during preg- nancy . Thorax 1996 ; 51 : 411 . 27 Murphy VE , Gibson PG , Smith R , Clifton VL . Asthma during preg- nancy: mechanisms and treatment implications . Eur Respir J 2005 ; 25 : 731 . 28 Gluck JC . The change of asthma course during pregnancy . Clin Rev Allergy Immunol 2004 ; 26 : 171 . 29 Kwon HL , Belanger K , Bracken MB . Effect of pregnancy and stage of pregnancy on asthma severity: a systematic review . Am J Obstet Gynecol 2004 ; 190 : 1201 . Severe Acute Asthma 337 69 Park - Wyllie L , Mazzotta P , Pastuszak A , et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta - analysis of epidemiological studies . Teratology 2000 ; 62 : 385 . 70 Bracken MB , Triche EW , Belanger K , et al. Asthma symptoms, sever- ity, and drug therapy: a prospective study of 2205 pregnancies . Obstet Gynecol 2003 ; 102 : 739 . 71 Reinisch JM , Simon NG , Karow WG , Gandelman R . Prenatal expo- sure to prednisone in humans and animals retards intrauterine growth . Science 1978 ; 202 : 436 . 72 Robert E , Vollset SE , Botto L , et al. Malformation surveillance and maternal drug exposure: the Madre Project . Int J Risk Safety Med 1994 ; 6 : 75 – 118 . 73 Carmichael SL , Shaw GM . Maternal corticosteroid use and risk of selected congenital anomalies . Am J Med Genet 1999 ; 86 : 242 – 244 . 74 Czeizel AE , Rockenbauer M . Population - based case - control study of teratogenic potential of corticosteroids . Teratology 1997 ; 56 : 335 – 340 . 75 Schatz M . Asthma during pregnancy: interrelationships and manage- ment . Ann Allergy 1992 ; 68 : 123 – 133 . 76 Metzer MJ , Turner E , Patterson R . The safety of immunotherapy during pregnancy . J Allergy Clin Immunol 1978 ; 61 : 268 – 272 . 77 Metzger MJ . Indications for allergen immunotherapy during preg- nancy . Compr Ther 1990 ; 16 : 17 – 26 . 78 Liccardi G , Cazzola M , Canonica GW , et al. General strategy for the management of bronchial asthma in pregnancy . Respir Med 2003 ; 97 : 778 – 789 . 79 Juniper EF , Daniel EE , Roberts RS , et al. Improvement in airway responsiveness and asthma severity during pregnancy. A prospective study . Am Rev Respir Dis 1989 ; 140 : 924 . 80 Nelson - Piercy C . Respiratory disease . In: Nelson - Piercy C . Handbook of Obstetric Medicine . Oxford : Isis Medical Media , 1997 : 45 – 65 . 81 Schatz M , Weinberger S . Management of asthma during pregnancy . In: Rose BD , ed. UpToDate . Wellesley, MA : UpToDate , 2006 . 82 Nelson - Piercy C , DeSwiet M . Asthma during pregnancy . Fetal Maternal Med Rev 1994 ; 6 : 181 – 189 . 83 Smith AP . The effects of intravenous infusion of graded doses of prostaglandin F2 α and E2 on lung resistance in patients undergoing termination of pregnancy . Clin Sci 1973 ; 44 : 17 – 25 . 84 Crawford JS . Bronchospasm following ergometrine . Anesthesiology 1980 ; 35 : 397 – 398 . 85 American Academy of Pediatrics Committee on Drugs . Transfer of drugs and other chemicals into human milk . Pediatrics 1989 ; 84 : 924 – 936 . 55 Michigan Medicaid Study , Briggs GG , Freeman RA , Yaffe SJ . Drugs in Pregnancy and Lactation , 4th edn . Baltimore, MD : Williams and Wilkins , 1994 . 56 Schatz M , Zeiger RS , Harden K , et al. The safety of asthma and allergy medications during pregnancy . J Allergy Clin Immunol 1997 ; 100 : 301 – 306 . 57 Schuh S , Johnson DW , Callahan S , et al. Effi cacy of frequent nebu- lized ipratropium bromide added to frequent high - dose albuterol therapy in severe childhood asthma . J Pediatr 1995 ; 126 : 639 – 645 . 58 Lin RY , Pesola GR , Bakalchuk L , et al. Superiority of ipratropium plus albuterol over albuterol alone in the emergency department manage- ment of adult asthma: a randomized clinical trial . Ann Emerg Med 1998 ; 31 : 208 – 213 . 59 National Asthma Education and Prevention Program Expert Panel Executive Summary Report . Guidelines for the Diagnosis and Management of Asthma, Update on Selected Topics 2002 . Publication No. 02 - 5075 . Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute, 2002 . 60 Busse WW . NAEPP Expert Panel Report . J Allergy Clin Immunol 2005 ; 115 : 34 . 61 Connelly TJ , Ruo TI , Frederiksen MC , Atkinson AJ . Characterization of theophylline binding to serum proteins in pregnant and nonpreg- nant women . Clin Pharmacol Ther 1990 ; 47 : 68 . 62 Schatz M , Dombrowski MP , Wise R , et al. The relationship of asthma medication use to perinatal outcomes . J Allergy Clin Immunol 2004 ; 113 : 1040 . 63 Labovitz E , Spector S . Placental theophylline transfer in pregnant asthmatics . JAMA 1982 ; 247 : 786 – 788 . 64 Arwood LL , Dasta JF , Friedman C . Placental transfer of theophylline: two case reports . Pediatrics 1979 ; 63 : 844 – 846 . 65 Cockcroft DW , Murdock KY . Comparative effects of inhaled salbu- tamol, sodium cromoglycate, and beclomethasone dipropionate on allergen - induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine . J Allergy Clin Immunol 1987 ; 79 : 734 – 740 . 66 Namazy JA , Schatz M , Long L , et al. Use of inhaled steroids by preg- nant asthmatic women does not reduce intrauterine growth . J Allergy Clin Immunol 2004 ; 113 : 427 . 67 Bakhireva LN , Jones KL , Schatz M , et al. Asthma medication use in pregnancy and fetal growth . J Allergy Clin Immunol 2005 ; 166 : 503 . 68 Fitzsimons R , Greenberger PA , Patterson R . Outcome of pregnancy in women requiring corticosteroids for severe asthma . J Allergy Clin Immunol 1986 ; 78 : 349 . 338 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 24 Acute Lung Injury and Acute Respiratory Distress Syndrome ( ARDS ) During Pregnancy Antara Mallampalli , Nicola A. Hanania & Kalpalatha K. Guntupalli Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA Introduction Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are uncommon but important causes of acute hypox- emic respiratory failure during pregnancy. Current literature regarding these complications in pregnancy is limited largely to case series, and most of our current approach to the management of ALI/ARDS during pregnancy is based on data from studies performed in non - pregnant patients. This chapter reviews the current understanding of these syndromes, focusing on the defi - nition, clinical presentation, etiologies, and impact of ALI and ARDS, as well as on treatment approaches during pregnancy. Defi nitions The fi rst cohesive description of the acute respiratory distress syndrome was published in 1967 by Ashbaugh and colleagues [1] , who used the term ARDS in describing a series of 12 patients with acute onset of hypoxemic respiratory failure characterized by diffuse pulmonary infi ltrates on CXR, severe hypoxemia not responsive to supplemental oxygen, and reduced lung compli- ance. Although initially termed “ adult respiratory distress syn- drome ” in the literature (to distinguish it from the neonatal respiratory distress syndrome seen in prematurity), the condition was later renamed “ acute ” respiratory distress syndrome when it became clear that the same clinical and pathophysiological process can occur in children as well as adults. Early literature on the syndrome used a variety of criteria to make the diagnosis, but these were not well standardized. In 1994, the fi ndings of the American - European Consensus Conference on ARDS were pub- lished and laid out the criteria currently in use to defi ne ARDS (see Table 24.1 ): (i) acute onset of respiratory distress, (ii) a P a O 2 / F i O 2 ratio of ≤ 200 (regardless of PEEP), (iii) bilateral pulmonary infi ltrates on chest X - ray, and (iv) a pulmonary artery occlusion (wedge) pressure ≤ 18 mmHg or absence of clinical evidence of left atrial hypertension [2] . The consensus conference also defi ned the term “ acute lung injury ” (ALI) to refer to the same clinical syndrome when associated with a milder degree of gas exchange abnormality, i.e. a P a O 2 /F i O 2 ≤ 300 [2] . It is important to note that a pulmonary artery catheter is not required to make the diagnosis in the absence of clinical suspicion of left heart dysfunction. However, cardiogenic pulmonary edema and volume overload are always important considerations in the differential diagnosis of ALI and ARDS, and may be especially an issue in pregnancy because of the greater predisposition of these patients for developing volume overload and/or concomitant peripartum cardiomyopathy. Epidemiology of ALI and ARDS The reported incidences of ALI and ARDS have varied over the years due in part to changes in the accepted defi nitions of the syndromes. Several epidemiologic studies have since been pub- lished utilizing the now accepted American - European Consensus Conference defi nitions, allowing more uniform comparisons. One early study from Sweden, Denmark, and Iceland reported an incidence of 17.9 per 100 000 person - years for ALI and 13.5 per 100 000 person - years for ARDS [3] . In the United States, a recent study using the screening data from the ARDS Network clinical trials found an estimated incidence of 64.2 per 100 000 person - years for ALI [4] . There is only limited data on the incidence of ALI and ARDS in pregnancy. Catanzarite and colleagues reported an incidence of 1 per 6227 deliveries based on their series of 28 patients [5] . Other studies in the obstetric population also have reported similar numbers for ALI/ARDS incidence [6,7] . Clinical p resentation and p athophysiology of ALI / ARDS Patients with ALI and ARDS typically present with acute hypox- emic respiratory failure, with symptoms including dyspnea, . 23.2 . Patients with acute asthma who present to the emergency department require expeditious evaluation and care. Initial care is no different than in non - pregnant patients and includes. requiring corticosteroids for severe asthma . J Allergy Clin Immunol 1986 ; 78 : 349 . 338 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy Treatment Treatment plans are essential in the care of asthmatic patients. They allow for patients to become more involved in their own care and assist in the formation of an action plan