Abstract
Patients with asthma, infection, respiratory failure, or cystic fibrosis and patients who smoke cigarettes may have reversible airway obstruction. In patients with airway hyperresponsiveness, tracheal intubation provides one of the most significant stimuli for bronchospasm during the perioperative period. Inhaled beta 2 -adrenergic agonists are the most effective therapy for perioperative bronchospasm. Most bronchodilators also produce uterine relaxation. However, their administration by aerosol should minimize their effects on uterine tone. Neuraxial anesthesia is often the anesthetic technique of choice in patients with respiratory disease because it does not require tracheal intubation. Techniques of neuraxial anesthesia should be modified to reduce the likelihood of a high thoracic motor block in patients with significant respiratory disease.
Keywords
Asthma, Cigarette smoking, Cystic fibrosis, Respiratory failure, Pregnancy, Neuraxial anesthesia
Chapter Outline
Asthma, 1231
Definition, 1231
Epidemiology, 1231
Pathophysiology, 1231
Diagnosis, 1233
Interaction with Pregnancy, 1233
Medical Management, 1234
Obstetric Management, 1236
Anesthetic Management, 1236
Cigarette Smoking, 1238
Epidemiology, 1238
Pathophysiology, 1238
Interaction with Pregnancy, 1238
Medical Management, 1238
Anesthetic Management, 1239
Cystic Fibrosis, 1239
Epidemiology, 1239
Pathophysiology, 1239
Diagnosis, 1239
Interaction with Pregnancy, 1239
Medical Management, 1240
Obstetric Management, 1240
Anesthetic Management, 1240
Respiratory Failure, 1240
Epidemiology, 1240
Pathophysiology, 1240
Diagnosis, 1241
Interaction with Pregnancy, 1241
Medical Management, 1241
Obstetric Management, 1242
Anesthetic Management, 1242
Asthma
Definition
Asthma is defined by the presence of the following three characteristic findings: (1) reversible airway obstruction, (2) airway inflammation, and (3) airway hyperresponsiveness. Airway obstruction produces the clinical manifestations of wheezing, cough, and dyspnea. Airway inflammation modulates the course of asthma by independently producing airway obstruction and enhancing airway hyperresponsiveness. Airway hyperresponsiveness is marked by exaggerated responses to a wide variety of bronchoconstrictor stimuli, including histamine, methacholine, prostaglandin F 2α , hypo-osmotic solutions, and cold air.
Epidemiology
Asthma is an increasingly common problem among young, otherwise healthy women of childbearing age. From 2001 to 2010, the prevalence of asthma in the United States increased from 7.3% to 8.4%.
The prevalence of asthma in women of childbearing age also continues to rise. The rate was approximately 3% in the 1990s and has increased to approximately 8.8% in the early 2000s.
Pathophysiology
Asthma is believed to occur under a variety of environmental influences in the presence of genetic susceptibility. The underlying defect that produces the clinical syndrome of asthma is unknown. The most important potential mechanisms are (1) an enhancement of contractility or an impairment of relaxation of airway smooth muscle, (2) a neural imbalance, (3) airway inflammation, and (4) changes in the function of the airway epithelium.
Airway Smooth Muscle
Contraction of airway smooth muscle is believed to be the most important factor in producing acute airway obstruction. For many years, an enhancement of airway smooth muscle responsiveness to contractile agonists was assumed to be a major mechanism of asthma. To test this hypothesis, investigators attempted to correlate airway responsiveness in vivo and in vitro in humans and in the basenji-greyhound dog model of asthma. These studies did not demonstrate a significant correlation between the airway response to histamine or cholinergic agonists in vivo and airway smooth muscle contraction in vitro. Some studies actually demonstrated a negative correlation between the in vivo and in vitro responses, suggesting that diminished responsiveness may represent a chronic adaptive response of airway smooth muscle.
Instead of an enhancement in responsiveness to contractile stimuli, a reduction in responsiveness to relaxant stimuli may contribute to airway obstruction. One study demonstrated impaired relaxant responses to isoproterenol in airway smooth muscle from human asthmatic subjects in comparison with the responsiveness of airway smooth muscle from controls. Other evidence substantiates the presence of impaired airway relaxation in asthmatic subjects in vivo. Although the mechanism for this effect is poorly understood, a reduction in airway sensitivity to beta-adrenergic agonists could contribute to airway hyperresponsiveness by altering the balance between constricting and dilating influences.
Neural Components
A balance between constricting and dilating influences also exists with respect to the autonomic nervous system. A shift in this balance, with an increase in constricting influences, may be a mechanism of asthma.
The parasympathetic nervous system provides the dominant constrictor input to the airways ( Fig. 52.1 ). Efferent cholinergic fibers travel in the vagus nerve to synapse in ganglia within the airway wall. Postganglionic fibers release acetylcholine to activate muscarinic receptors and stimulate airway smooth muscle contraction. A negative feedback system limits release of acetylcholine from nerve terminals. Muscarinic autoreceptors, or receptors on the nerve ending, also are activated by acetylcholine and inhibit further release of acetylcholine from the nerve terminal.
The importance of exaggerated cholinergic efferent activity in the pathogenesis of airway hyperreactivity has been debated extensively. The relatively limited efficacy of anticholinergic agents in relieving clinical bronchospasm, as well as growing evidence supporting other mechanisms, suggests that this pathway has a limited role in the pathophysiology of asthma. However, this mechanism appears to be very important in the perioperative management of asthmatic subjects. Reflex stimulation of airway smooth muscle by placement of a tracheal tube represents one of the most important causes of bronchospasm in the perioperative period.
An alternative mechanism by which the parasympathetic nervous system may contribute to airway hyperresponsiveness is through dysfunction of the muscarinic autoreceptors. Dysfunction of these receptors allows increased postganglionic release of acetylcholine after reflex stimulation. This mechanism is well established in a guinea pig model of viral infection and may explain the airway hyperresponsiveness that occurs for several weeks after an upper respiratory tract infection, although additional autoreceptor-independent mechanisms may also be present. The role of this mechanism in the pathophysiology of clinical asthma is unclear.
The sympathetic nervous system primarily acts to decrease airway tone. In contrast to the parasympathetic nervous system, sympathetic innervation of airway smooth muscle in human subjects is either sparse or absent. Circulating catecholamines activate beta-adrenergic receptors in airway smooth muscle and provide the primary sympathetic efferent input to human airways. Because airways of normal human subjects do not become hyperresponsive after beta-adrenergic blockade, it is unlikely that impaired catecholamine secretion contributes significantly to the pathogenesis of asthma.
The alpha-adrenergic system is thought to play a relatively minor role in determining the state of airway responsiveness. Although alpha-adrenergic receptors are present in human airways, the protective effects of alpha-adrenergic antagonists have been disappointing and can be attributed to other properties, such as antihistamine activity.
In addition to cholinergic and adrenergic input, a third neural system, the nonadrenergic noncholinergic (NANC) system, provides efferent nerves to the airways. Both constricting and dilating pathways have been identified. Nitric oxide serves as the inhibitory NANC neurotransmitter in human airways. Potentially, a relative increase in constricting influences or a decrease in dilating influences in the NANC system could contribute to asthma. However, asthmatic subjects demonstrated no deficit in NANC inhibitory pathways, and inhibition of NANC excitatory neurotransmission did not improve airway hyperresponsiveness. Thus, current evidence does not support imbalance of the NANC system as a major mechanism of asthma.
Airway Inflammation
Airway inflammation appears to serve primarily as a modulating influence in asthma. Inflammation is certainly present in some but not all asthmatic subjects. The process of inflammation involves the occurrence of airway wall edema and infiltration of the mucosa by a variety of inflammatory cells, including neutrophils, mast cells, helper T lymphocytes, macrophages, and eosinophils. These cells produce and release mediators of inflammation, such as histamine, leukotrienes, platelet-activating factor, prostaglandins, thromboxanes, cytokines, serotonin, and nitric oxide. Mediators can modulate airway responsiveness by stimulating airway smooth muscle contraction, directing migration of inflammatory cells, modifying neural control of the airways, increasing mucosal permeability, or disrupting airway epithelium. In addition, airway inflammation can reduce airway diameter. Airway hyperresponsiveness is correlated with increased baseline airway tone. The overall importance of inflammation in asthma has been debated. Although inflammation appears to modulate the course of asthma, other factors certainly contribute to the pathogenesis.
Airway Epithelium
The epithelium provides a barrier to protect the subepithelial layers against stimuli that could provoke bronchospasm. Airways of asthmatic subjects demonstrate areas of epithelial destruction, and the clinical significance of this finding has been demonstrated.
The epithelium not only serves as a barrier but also plays an active role in the maintenance of airway tone. The epithelium produces constricting and dilating factors. An alteration in the balance between these factors could alter airway responsiveness. The relative importance of alterations in epithelial function in the pathogenesis of asthma is unknown.
Diagnosis
Medical History
The classic symptoms of asthma include wheezing, cough, dyspnea, and chest tightness. A patient’s medical history also should include information about the pattern and severity of the symptoms, precipitating and aggravating factors, and the duration and course of these symptoms.
Physical Examination
Physical examination is directed to the respiratory tract. Auscultation of the chest may reveal wheezing and a prolonged phase of expiration.
Laboratory Studies
Laboratory studies that aid in the diagnosis of asthma depend on findings from the medical history and physical examination. In general, pulmonary function tests are useful to document the severity and establish the reversibility of obstruction ( Box 52.1 ). In the absence of additional findings, other tests are not as useful in establishing the diagnosis of asthma. Bronchoprovocation tests (with agents such as methacholine or histamine) are used when the history and physical examination strongly suggest the presence of asthma but spirometry does not show airway obstruction.
Forced Vital Capacity (FVC)
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The volume of gas exhaled after maximal inspiration
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May be reduced in asthma
Forced Expiratory Volume in 1 Second (FEV 1 )
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The volume exhaled in the first second after maximal inspiration
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May be reduced in asthma
FEV 1 /FVC < 0.75 in Asthma
Interaction with Pregnancy
Effects of Pregnancy on Asthma
The overall course of asthma has been reported to improve, worsen, or remain the same during pregnancy. Although earlier evidence suggested that patients with more severe asthma are more likely to experience deterioration during pregnancy, other studies indicate that asthma severity during pregnancy is similar to severity during the year before pregnancy, provided that patients continue to use their prescribed medication during pregnancy. Even mild asthma can become significantly more severe if women discontinue their prescribed medication during pregnancy. A likely reason for the variation in the results of published studies is the difference in methods of assessing the severity of asthma. Most studies have used either clinical symptoms or requirements for pharmacologic therapy as indicators of the course of the disease. These measures do not correlate with objective measures of airway obstruction. Juniper et al. measured methacholine sensitivity before, during, and after pregnancy. Measurements of sensitivity to methacholine made during the second and third trimesters were lower than preconception or postpartum measurements ( Fig. 52.2 ). Although these findings suggest a reduction in airway hyperresponsiveness during pregnancy, the limited study population (16 subjects) makes extrapolation of the data to the general population unclear. Conversely, a small ( n = 20) prospective study showed temporary declines in pulmonary function between 21 and 28 weeks’ gestation that returned to baseline later in the pregnancy. Exacerbations of asthma during labor and delivery occur in as many as 20% of subjects.
A number of mechanisms may be responsible for the changes in the clinical course of asthma during pregnancy ( Box 52.2 ). An increase in the progesterone level is thought to be one mechanism that improves asthma during pregnancy. Progesterone relaxes uterine and gastrointestinal smooth muscle and may or may not have similar effects on airway smooth muscle. However, Juniper et al. did not demonstrate a strong association between methacholine responsiveness and progesterone levels during pregnancy, suggesting that progesterone does not play a central role in attenuating airway hyperresponsiveness. In contrast, progesterone may actually worsen asthma by enhancing inflammation. Thus, effects of pregnancy on asthma appear to involve a number of factors other than direct effects of hormones on airway smooth muscle.
Factors That May Improve Asthma
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Progesterone-induced relaxation of airway smooth muscle
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Increased production of bronchodilating prostaglandins
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Higher circulating cortisol level
Factors That May Worsen Asthma
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Decreased sensitivity to beta-adrenergic agonists
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Increased production of bronchoconstricting prostaglandins
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Reduced sensitivity to circulating cortisol because of binding of steroid hormones (e.g., progesterone) to cortisol receptors
Effects of Asthma on the Parturient and Fetus
Many investigators have questioned whether maternal asthma adversely affects perinatal outcome. Differences in study design (e.g., retrospective, prospective) and differences in severity and treatment of asthma may account for different study results. Some studies have reported an increased incidence of preeclampsia, cesarean delivery, low-birth-weight (LBW) infants, preterm labor, antepartum and postpartum hemorrhage, and perinatal mortality. Diabetes mellitus appears to be more common among asthmatic patients treated with corticosteroids. Severe or poorly controlled asthma is a predictor of adverse outcome. Although asthma in pregnancy is associated with an increased risk for adverse perinatal outcomes, a meta-analysis of cohort studies suggested that active asthma management, which is intended to reduce the exacerbation rate, may reduce the risk for perinatal complications, particularly preterm delivery. No controlled studies have documented better perinatal outcome with aggressive asthma treatment. Potential mechanisms of increased perinatal morbidity and mortality in patients with uncontrolled asthma include hypoxemia and hypocapnia, inflammation, and altered placental function from asthma-associated mediator release. Siddiqui et al. have documented an association between preeclampsia and airway hyperresponsiveness and have proposed that the mechanism involves an interaction between mast cells and smooth muscle. A large prospective study is needed to confirm this association.
Medical Management
Pharmacologic therapy for asthma during pregnancy is directed toward avoiding acute exacerbations and episodes of status asthmaticus. Ideally, management should begin before conception. Although general principles typically dictate that unnecessary medication should be avoided during pregnancy, studies investigating the effects of asthma on perinatal outcome suggest that the risks for uncontrolled asthma are significantly higher than medication-associated risks. Medications that are currently used to treat asthma fall into two general categories: bronchodilators and antiinflammatory agents. These agents generally are safe for the fetus. The prophylactic use of antibiotics is unnecessary.
Bronchodilators
Beta-adrenergic agonists exert beneficial effects in asthmatic patients by activation of β 2 -adrenergic receptors, which mediate a number of processes ( Box 52.3 ). Short-acting beta-adrenergic agonists represent the most effective therapy for acute exacerbations of asthma. Daily use of long-acting beta-adrenergic agonists is controversial. Long-acting beta-adrenergic agonist therapy is associated with a significant increase in the risk for death, but controlled studies have not confirmed a cause-and-effect relationship. Certain genetic polymorphisms affect responses to short-acting but not long-acting beta-adrenergic agonists, leading to hopes that a personalized approach to therapy would improve clinical efficacy. Although regular use of beta-adrenergic agonists in asthma may be beneficial in conjunction with other forms of therapy, these agents do not appear to provide optimal control when used alone. Conversely, no compelling evidence requires that beta-adrenergic agonists be discontinued after conception or that their use be reserved for treatment of an acute exacerbation.
