Browse the corpus

CHAPTER 69:  Acute Asthma and Sta tus Asthma ticus      461 guidelines suggest that a history of spontaneous pneumothorax is a contraindication to underwater diving unless treated by surgical pleu rectomy and normal lung function exists.21 DISPOSITION Discharge to home patients with a primary spontaneous pneumothorax successfully treated with observation or with catheter aspiration if the pneumothorax does not increase in size over 3 to 6 hours and symptoms resolve or do not worsen. Observe for longer or admit the remaining patients. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Acute Asthma and Status Asthmaticus Tadahiro Goto Kohei Hasegawa INTRODUCTION AND EPIDEMIOLOGY Asthma is a chronic inflammatory disorder characterized by increased responsiveness of the airways to multiple stimuli. In susceptible indi viduals, the inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes—acute asthma—usually have wide spread and varying airflow obstruction. Although most acute asthma episodes improve spontaneously or within minutes to hours with treatment, with symptom-free intervals in between, many patients with asthma develop chronic airflow limita tion. This impacts the diagnosis and management of episodes and the attempts to prevent recurrent acute asthma. Asthma affects approximately 8% of the U.S. population, is the most common chronic disease of childhood (9% prevalence), and has a similar prevalence in developed nations around the world. 1-3 Approximately one half of asthma cases develop before the age of 10 years, and another one third develop by the age of 40 years. PATHOPHYSIOLOGY Asthma sufferers have an abnormal accumulation of eosinophils, lym phocytes, mast cells, macrophages, dendritic cells, and myofibroblasts in airways. The pathophysiologic hallmark of asthma is a reduction in airway diameter caused by smooth muscle contraction, vascular congestion, bronchial wall edema, and thick secretions. These changes create pulmonary function changes, increased work of breathing, and abnormal distribution of pulmonary blood flow ( Table 69-1). Large and small airways contain plugs composed of mucus, serum proteins, inflammatory cells, and cellular debris. Inflammation affects all bron chial pulmonary structures. Asthma is a continuum from acute bronchospasm through airway inflammation to permanent airway remodeling. Airway remodeling, with sub-basement membrane thickening, subepithelial fibrosis, airway smooth muscle hypertrophy and hyperplasia, angiogenesis, and mucous gland hyperplasia and hypersecretion, can become a trigger for nonre versible loss of lung function. Acute allergic bronchoconstriction results from immunoglobulin E– dependent release of mediators from mast cells. These mediators include histamine, leukotrienes, tryptase, and prostaglandins that directly CHAPTER contract airway smooth muscle.4 Bronchospasm induced by aspirin and other NSAIDs also involves mediator release from airway cells.4 Airway inflammation occurs as inhaled antigens activate immunoglobulin E, mast cells, dendritic cells, T helper cells, and epithelial cells in the airway and induce inflammatory mediators and cytokines. In turn, this initiates a cascade of inflammatory response, which is multicellular, redundant, and self-amplifying.

4 Airway inflammation occurs as inhaled antigens activate immunoglobulin E, mast cells, dendritic cells, T helper cells, and epithelial cells in the airway and induce inflammatory mediators and cytokines. In turn, this initiates a cascade of inflammatory response, which is multicellular, redundant, and self-amplifying. Acute asthma is an exaggerated airway response to a variety of exter nal exposures. Viral acute respiratory infections are the most common acute asthma stimulus, 5 accounting for 40% to 80% of episodes in adults and 80% in children. 6 Exercise is another common precipitant of acute asthma. Environmental conditions, such as atmospheric pollutants and indoor antigens (e.g., mold, house dust mites, cockroaches, and animal dander), trigger acute asthma and may result in severe cases. Occupa tional exposures, such as metal salt, wood and vegetable dust, pharma ceuticals, industrial chemicals, plastics, biological enzymes, vapors, gases, and aerosols, also may stimulate acute asthma. Agents such as aspirin, β-blockers, and NSAIDs may prompt acute asthma. Exposure to cold air alone can induce acute bronchospasm. Endocrine factors, such as changing levels of estradiol and progesterone during the normal men strual cycle and pregnancy, contribute to the level of airway reactivity. Emotional stress also can produce acute asthma. CLINICAL FEATURES Early recognition of acute asthma and treatment before the exacerbation becomes severe are the essentials of acute asthma management in the ED. Focus the initial assessment on history and physical examination; for most patients, an objective assessment of lung function (e.g., peak expiratory flow rate [PEFR]) aids assessment. The typical symptoms of acute asthma include dyspnea, wheezing, and cough. Many, but not all, patients will relay the history of asthma. Other historical features guide care for acute asthma 8-11 (Table 69-2). In addition, because patients who are at the highest risk for fatal asthma require special attention, seek out risk factors for a fatal exacerbation. The severity of acute asthma is categorized based on clinical features 8-11 (Table 69-3). Physical examination includes general appearance (e.g., respiratory distress, level of consciousness), vital signs (e.g., tachycardia, tachypnea), and chest findings (e.g., wheezing). Wheezing can be an unreliable indicator of airflow obstruction in acute asthma. A silent chest with out wheezing occurs in extremely severe airflow obstruction. 12 Use of accessory muscles, inability to speak in full sentences or phrases, and presence of pulsus paradoxus help identify severe acute asthma. 8 Look also for concomitant illnesses (e.g., pneumonia, pneumothorax) or mimicking conditions such as upper airway obstruction from foreign bodies and vocal cord dysfunction (Table 69-4). The latter is a common reason why patients who fail therapy and have frequent ED return visits get labeled as having “refractory asthma”; such patients simply do not have lower airway disease. TABLE 69-1 Physiologic Consequences of Airflow Obstruction in Acute Asthma •   Increased airway resistance •   Decreased maximum expiratory flow rates •   Air trapping •   Increased airway pressure •   Barotrauma •   Adverse hemodynamic effects •   Ventilation–perfusion imbalance •   Hypoxemia •   Hypercarbia •   Increased work of breathing •   Pulsus paradoxus •   Respiratory muscle fatigue with ventilatory failure Tintinalli_Sec08_p0425-0472.indd 461 8/1/19 2:10 PM

•   Air trapping •   Increased airway pressure •   Barotrauma •   Adverse hemodynamic effects •   Ventilation–perfusion imbalance •   Hypoxemia •   Hypercarbia •   Increased work of breathing •   Pulsus paradoxus •   Respiratory muscle fatigue with ventilatory failure Tintinalli_Sec08_p0425-0472.indd 461 8/1/19 2:10 PM 462 SECTION 8: Pulmonary Disorders TABLE 69-2 Key History Points in Patients With Acute Asthma 8-11 Symptoms Pattern Disease History Risk Factors for Death From Asthma Cough Perennial and/or seasonal Cigarette smoking Past history of severe exacerbation Wheezing Continual or episodic Present management and medications ≥2 hospitalizations for asthma in the past year Shortness of breath Onset Medication regimen adherence >3 ED visits for asthma in the past year Chest tightness Duration History of corticosteroid use (chronic and/or intermittent) >2 canisters per month of inhaled short-acting β2-agonist Sputum production Frequency Intensive care admissions Difficulty perceiving airflow obstruction or its severity Fever Aggravating factors History of intubation Low socioeconomic status or inner-city resident Usual pattern of exacerbation and outcome Best spirometry measures Illicit drug use Psychiatric disease or medical comorbidities TABLE 69-3 Classifying Severity of Acute Asthma in Patients Aged >12 Years Old and Adults*

rity Fever Aggravating factors History of intubation Low socioeconomic status or inner-city resident Usual pattern of exacerbation and outcome Best spirometry measures Illicit drug use Psychiatric disease or medical comorbidities TABLE 69-3 Classifying Severity of Acute Asthma in Patients Aged >12 Years Old and Adults* Symptoms and Signs Initial PEF (or FEV1) Clinical Course Mild Dyspnea only with activity PEF ≥70% predicted or personal best Prompt relief with inhaled SABA. Moderate Dyspnea interferes with or limits usual activity PEF 40%–69% predicted or personal best Relief from frequent inhaled SABA. Symptoms for 1–2 d after oral corticosteroids begun. Severe Dyspnea at rest; interferes with conversation PEF <40% predicted or personal best Partial relief from frequent inhaled SABA. Symptoms for ≥3 d after oral corticosteroids begun. Subset: life-threatening Too dyspneic to speak; perspiring PEF <25% predicted or personal best Minimal or no relief from frequent inhaled SABA; IV steroids; adjunctive therapy; needs ED or intensive care unit. *The presence of several parameters, but not necessarily all, indicates the general classification of the exacerbation. Many of these parameters have not been systemically studied, so they serve only as general guides. Abbreviations: FEV1 = forced expiratory volume in 1 second; PEF = peak expiratory flow; SABA = shortacting β 2-agonist. Source: www.nhlbi.nih.gov/files/docs/guidelines/asthsumm.pdf (National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services: NIH Publication Number 08-5846, October 2007, Fig. 20). Accessed June 15, 2018. TABLE 69-4 Important Asthma Mimickers •   Acute heart failure (“cardiac asthma”) •   Upper airway obstruction •   Pulmonary embolism •   Aspiration of foreign body or gastric acid •   Tumors/disorders causing endobronchial obstruction •   Interstitial lung disease •   Vocal cord dysfunction DIAGNOSIS AND PATIENT MONITORING Physical examination findings and subjective symptoms do not neces sarily correlate well with the severity of airflow obstruction, making objective measures valuable. Forced expiratory volume in 1 second (FEV 1) and PEFR are key objective measures of severity of acute asthma. The FEV1 advantage is that in contrast to PEFR, it can help distinguish between poor effort, restrictive lung disorders, vocal cord dysfunction, and obstructive disorders (e.g., asthma). PEFR measurements using peak flow meter provide a reasonable estimate of the severity of acute asthma in the ED. In addition, PEFR measurements help monitor the response to the treatment. Repeat either FEV 1 or PEFR because comparing measures at ED presentation and 1 hour after treatment is the best predictor of hospitalization in patients with acute asthma. 13,14 Patient education and cooperation are essential for these measurements to be reliable.8-11 Pulse oximetry assesses oxygen saturation during treatment. Arterial blood gas measurement is not needed in patients with mild to moderate asthma exacerbation and should be reserved for suspected hypoventila tion with carbon dioxide retention and respiratory acidosis. With acute asthma, ventilation is stimulated, resulting in a decrease in partial pressure of arterial carbon dioxide (Pa co 2); if a normal or slightly elevated Paco 2 (e.g., >42 mm Hg) exists, think of extreme airway obstruction, fatigue, and potential acute ventilatory failure. Patients with impending respiratory failure almost always have clinical evidence of severe acute asthma or spirometry demonstrating a PEFR or FEV 1 of <25% pre dicted. The use of capnography in acute asthma management is unclear.

ts, think of extreme airway obstruction, fatigue, and potential acute ventilatory failure. Patients with impending respiratory failure almost always have clinical evidence of severe acute asthma or spirometry demonstrating a PEFR or FEV 1 of <25% pre dicted. The use of capnography in acute asthma management is unclear. One small study reported good concordance between expired carbon dioxide levels measured by capnography and arterial carbon dioxide concentration, 15 but another reported differences of up to >10 mm Hg between the two approaches.16 Chest radiographs help to detect pneumothorax, pneumomediasti num, pneumonia, or other causes for symptoms (e.g., acute heart failure) or complications of acute asthma. Plain radiographs are not needed for all patients with acute asthma, but are better selectively used when there is suspicion for the previously mentioned conditions. In patients hospitalized for acute asthma, less than one third of patients have an abnormal chest radiograph. A CBC is not routinely needed and likely will show modest leukocy tosis secondary to administration of β-agonist therapy and/or corticosteroids. For patients with severe acute asthma (e.g., those hospitalized for acute asthma), serum total immunoglobulin E level and eosinophil quantification may aid chronic asthma management using biologic agents (e.g., anti–immunoglobulin E monoclonal antibody). 18,19 Routine ECG is also unnecessary and often normal or nondiagnostic, but may reveal right ventricular strain, abnormal P waves, or nonspecific ST- and T-wave abnormalities, which resolve with treatment. Use cardiac monitoring in older patients and those with coexisting heart disease. ACUTE ASTHMA STANDARD TREATMENT The goal is a rapid reversal of airflow obstruction by repetitive or continuous administration of inhaled β 2-agonists, adequate oxygenation, and decrease in inflammation. 8-11 Figure 69-1 shows the National Asthma Education and Prevention Program ED treatment algorithm.11  β -ADRENERGIC AGENTS Rapid-onset β2-adrenergic agonists are the preferred initial therapy for acute bronchospasm (Table 69-5). Stimulation of β1-receptors increases rate and force of cardiac contraction, whereas β2-adrenergic stimulation promotes bronchodilation and vasodilation. Tintinalli_Sec08_p0425-0472.indd 462 8/1/19 2:10 PM CHAPTER 69:  Acute Asthma and Sta tus Asthma ticus      463

One small study reported good concordance between expired carbon dioxide levels measured by capnography and arterial carbon dioxide concentration, 15 but another reported differences of up to >10 mm Hg between the two approaches.16 Chest radiographs help to detect pneumothorax, pneumomediasti num, pneumonia, or other causes for symptoms (e.g., acute heart failure) or complications of acute asthma. Plain radiographs are not needed for all patients with acute asthma, but are better selectively used when there is suspicion for the previously mentioned conditions. In patients hospitalized for acute asthma, less than one third of patients have an abnormal chest radiograph. A CBC is not routinely needed and likely will show modest leukocy tosis secondary to administration of β-agonist therapy and/or corticosteroids. For patients with severe acute asthma (e.g., those hospitalized for acute asthma), serum total immunoglobulin E level and eosinophil quantification may aid chronic asthma management using biologic agents (e.g., anti–immunoglobulin E monoclonal antibody). 18,19 Routine ECG is also unnecessary and often normal or nondiagnostic, but may reveal right ventricular strain, abnormal P waves, or nonspecific ST- and T-wave abnormalities, which resolve with treatment. Use cardiac monitoring in older patients and those with coexisting heart disease. ACUTE ASTHMA STANDARD TREATMENT The goal is a rapid reversal of airflow obstruction by repetitive or continuous administration of inhaled β 2-agonists, adequate oxygenation, and decrease in inflammation. 8-11 Figure 69-1 shows the National Asthma Education and Prevention Program ED treatment algorithm.11  β -ADRENERGIC AGENTS Rapid-onset β2-adrenergic agonists are the preferred initial therapy for acute bronchospasm (Table 69-5). Stimulation of β1-receptors increases rate and force of cardiac contraction, whereas β2-adrenergic stimulation promotes bronchodilation and vasodilation. Tintinalli_Sec08_p0425-0472.indd 462 8/1/19 2:10 PM CHAPTER 69:  Acute Asthma and Sta tus Asthma ticus      463 FEV1 or PEFR ≥40% (Mild-to-Moderate) • Oxygen to achieve Sao2 ≥90% • Inhaled SA BA by nebulilzer or MDI + valved holding chamber, up to 3 doses in first hour • Oral systemic corticosteroids if no immediate response or if patient recently took oral systemic corticosteroids Good Response • FEV 1 or PEFR ≥70% • Response sustained 60 minutes after last treatment • No distress • Ph ysical exam: normal Incomplete Response • FEV 1 or PEFR 40%–69% • Mild-to-moderate symptoms Poor Response • FEV 1 or PEFR <40% • Pco 2 ≥42 mm Hg • Ph ysical exam: symptoms severe, drowsiness, confusion Individualized decision re: hospitalization Moderate Exacerbation FEV 1 or PEFR 40%–69% predicted/personal best physical exam: moderate symptoms • Inhaled SA BA every 60 minutes • Oral systemic corticosteroid • Continue treatment 1–3 hours, provided there is improvement; make admit decision in <4 hours Severe Exacerbation FEV1 or PEFR <40% predicted/personal best Physical exam: severe symptoms at rest, accessory muscle use, chest retraction History: high-risk patient No improvement after initial treatment • Oxygen • Nebulized SABA+ipratropium, hourly or continuous • Oral systemic corticosteroids • Consider adjunct therapies Discharge Home • Continue treatment with inhaled SABAs. • Continue course of oral systemic corticosteroid. • Continue on ICS. For those not on long-term control therapy, consider initiation of an ICS. • Patient education (e.g., re view medications, review/initiate action plan, recommend close medical follow-up). • Before discharge, schedule follow-up appointment with primary care provider and/or asthma specialist in 1–4 weeks. FEV1 or PEFR <40% (Severe) • Oxygen to achieve Sao2 ≥90% • High-dose inhaled SA BA by MDI plus ipratropium by nebulization every 20 minutes or continuously for 1 hour • Oral systemic corticosteroids Impending or Actual Respiratory Arrest • Intubation and mechanical ventilation with 100% oxygen • Nebulized SABA and ipratropium • IV corticost eroids • See treatment under Status Asthmaticus Discharge Home • Continue treatment with inhaled SABA • Continue cour se of oral systemic corticosteroid • Consider initiation of an ICS • Patient education Review medicine use Review/initiate action plan Recommend close medical follow-up Admit to Hospital Ward • Oxygen • Inhaled SA BA • Systemic (PO or IV) corticosteroid • Consider adjunct therapies • Monitor vital signs, FEV 1 or PEFR, Sao2 Admit to Hospital Intensive Care • Oxygen • Inhaled SA BA hourly or continuously • IV corticost eroid • Consider adjunct therapies • Possible intubation and mechanical ventilation Initial Assessment Brief history, physical examination (auscultation, use of accessory muscles, heart rate, respiratory rate), PEFR or FEV1, oxygen saturation, and other tests as indicated Repeat Assessment Symptoms, physical examination, PEFR, o2 saturation, other tests as needed Admit to Hospital Intensive Care (see box below) Improve Improve FIGURE 69-1. Management of asthma exacerbations: ED and hospital-based care. FEV1 = forced expiratory volume in 1 second; ICS = inhaled corticosteroid; MDI = metered-dose inhaler; PEFR = peak expiratory flow rate; SABA = short-acting β2-agonist; Sao2 = oxygen saturation by pulse oximetry. [Source: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf (National Heart, Lung, and Blood Institute; National Institutes of Health; U.S.

second; ICS = inhaled corticosteroid; MDI = metered-dose inhaler; PEFR = peak expiratory flow rate; SABA = short-acting β2-agonist; Sao2 = oxygen saturation by pulse oximetry. [Source: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf (National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services: National Asthma Education and Prevention Program, Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Publication No. 08-4051. Bethesda, MD, National Institutes of Health, 2007). Accessed November 18, 2014.] Tintinalli_Sec08_p0425-0472.indd 463 8/1/19 2:10 PM

ment of Health and Human Services: National Asthma Education and Prevention Program, Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Publication No. 08-4051. Bethesda, MD, National Institutes of Health, 2007). Accessed November 18, 2014.] Tintinalli_Sec08_p0425-0472.indd 463 8/1/19 2:10 PM 464 SECTION 8: Pulmonary Disorders TABLE 69-5 β-Adrenergic, Anticholinergic, and Steroid Dosages of Drugs for Asthma Medication Dose Comments Inhaled β 2-Agonists Albuterol Nebulizer solution (0.63 milligram/3 mL, 1.25 milligrams/3 mL, 2.5 milligrams/3 mL, 5.0 milligrams/mL) 2.5–5 milligrams every 20 min for 3 doses, then 2.5–10 milligrams every 1–4 h, as needed, or 10–15 milligrams/h as continuous nebulization. Only selective β 2-agonists are recommended. For optimal delivery, dilute aerosols to minimum of 3 mL at gas flow of 6–8 L/min. Use large-volume nebulizers for continuous administration. May mix with ipratropium nebulizer solution. MDI (90 micrograms/puff) 4–8 puffs every 20 min up to 4 h, then every 1–4 h as needed. In mild-to-moderate exacerbations, MDI plus valved holding chamber is as effective as nebulized therapy with appropriate administration technique and coaching by trained personnel. Levalbuterol (R-albuterol) Nebulizer solution (0.63 milligram/3 mL, 1.25 milligrams/3 mL) 1.25–2.5 milligrams every 20 min for 3 doses, then 1.25–5 milligrams every 1–4 h, as needed. Levalbuterol administered in one half the milligram dose of albuterol provides comparable efficacy and safety. Has not been evaluated for continuous nebulization. MDI (45 micrograms/puff) See albuterol MDI dose. Systemic (Injected) Agents Epinephrine (α- and β-agonist) 1:1000 (1 milligram/mL) 0.3–0.5 milligram every 20 min for 3 doses SC or IM. No proven advantage of systemic therapy over aerosol. Terbutaline (β 2-agonist) (1 milligram/mL) 2 micrograms/kg may be given over 5 min, fol lowed by continuous infusion of 5 micrograms/ kg/h. No proven advantage of systemic therapy over aerosol. Anticholinergics/Combinations Ipratropium bromide Nebulizer solution (0.25 milligram/mL) 0.5 milligram every 20 min for 3 doses, then as needed. May mix in same nebulizer with albuterol. Should not be used as first-line therapy; should be added to SABA therapy for severe exacerbations. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized. MDI (18 micrograms/puff) Eight puffs every 20 min, as needed, up to 3 h. Should use with valved holding chamber and facemask for children <4 y. Studies have examined ipratropium bromide MDI for up to 3 h. Ipratropium with albuterol Nebulizer solution (each 3-mL vial contains 0.5 milligram of ipratropium bromide and 2.5 milligrams of albuterol) 3 mL every 20 min for 3 doses, then as needed. May be used for up to 3 h in the initial management of severe exacerbations. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized. MDI (each puff contains 18 micrograms of ipratropium bromide and 90 micrograms of albuterol) Eight puffs every 20 min as needed up to 3 h. Should use with valved holding chamber and facemask for children <4 y. Systemic Corticosteroids   Applies to all 3 corticosteroids for oral medications. Prednisone For inpatients:  oral “burst,”  use 40–80 milligrams/d in 1 or 2 divided doses until PEFR reaches 70% of predicted or personal best. For outpatients: oral “burst,” use 40–60 milligrams in 1 or 2 divided doses for 5–10 d. Methylprednisolone IV: 1 milligram/kg every 4–6 h. For outpatients: a single IM dose of 150 milligrams depot methylprednisolone may be used.19 Prednisolone 1–2 milligrams/kg/d for 5–10 d; may be divided twice daily.

r personal best. For outpatients: oral “burst,” use 40–60 milligrams in 1 or 2 divided doses for 5–10 d. Methylprednisolone IV: 1 milligram/kg every 4–6 h. For outpatients: a single IM dose of 150 milligrams depot methylprednisolone may be used.19 Prednisolone 1–2 milligrams/kg/d for 5–10 d; may be divided twice daily. More frequently used over prednisone in children due to increased palatability of available liquid formulations. Notes: There is no known advantage for higher doses of corticosteroids in severe asthma exacerbations, nor is there any advantage for IV administration over oral therapy provided GI transit time or absorption is not impaired. The course of systemic corticosteroids for an asthma exacerbation requiring an ED visit or hospitalization may last from 3 to 10 days. For corticosteroid courses of <1 week, there is no need to taper the dose. For slightly longer courses (e.g., up to 10 days), there probably is no need to taper, especially if patients are concurrently taking inhaled corticosteroids. Inhaled corticosteroids can be started at any point in the treatment of an asthma exacerbation. Abbreviations: MDI = metered-dose inhaler; PEFR = peak expiratory flow rate. Source: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf (National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services: National Asthma Education and Prevention Program, Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Publication No. 08-4051. Bethesda, MD, National Institutes of Health, 2007). Accessed June 20, 2019. β-Adrenergic drugs cause bronchodilation by stimulation of the enzyme adenyl cyclase, which converts intracellular adenosine triphos phate into cyclic adenosine monophosphate. β-Adrenergic drugs also inhibit mediator release and promote mucociliary clearance. The most common side effect of β-adrenergic drugs is skeletal muscle tremor. Patients also may experience nervousness, anxiety, insomnia, headache, hyperglycemia, palpitations, tachycardia, and hypertension. Clinical toxicity is rare and less common than undertreatment compli cations. Provoking dysrhythmias or myocardial ischemia is sporadic, especially in those without a prior history of coronary artery disease. The early-generation bronchodilators, such as epinephrine, are not β specific and have a short duration of action. Albuterol (racemic mixture) and levalbuterol (isomer form, Xopenex® ) are β2-adrenergic drugs. Both racemic albuterol and levalbuterol can be Tintinalli_Sec08_p0425-0472.indd 464 8/1/19 2:10 PM

ry disease. The early-generation bronchodilators, such as epinephrine, are not β specific and have a short duration of action. Albuterol (racemic mixture) and levalbuterol (isomer form, Xopenex® ) are β2-adrenergic drugs. Both racemic albuterol and levalbuterol can be Tintinalli_Sec08_p0425-0472.indd 464 8/1/19 2:10 PM CHAPTER 69:  Acute Asthma and Sta tus Asthma ticus      465 given as intermittent or continuous nebulization. 20-22 Levalbuterol costs 5 to 25 times more than albuterol, and it has no clear advantage over albuterol regarding improvement in symptoms, hospitalization, or tachycardia. Aerosol therapy with β 2-adrenergic drugs produces excellent bron chodilation and is favored over oral or parenteral routes. The aerosol route achieves topical administration of a relatively small dose of drug, thereby producing local effects with minimum systemic absorption and fewer side effects. Aerosol delivery occurs with a metered-dose inhaler coupled to a spacing device or with a compressor-driven nebulizer. 23 A spacing device attached to the inhaler improves drug deposition; when optimally used, metered-dose inhaler therapy delivers the most drug to target airways, better than nebulized therapy . Even with optimum technique, a maximum of 15% of the drug dose is retained in the lungs, regardless of the aerosol method used. Give aerosol treatments every 15 to 20 minutes or on a continuous basis. 24 SC epinephrine and terbutaline are options for patients unable to coordinate aerosolized or metereddose inhaler treatments, seen often in severe airflow-limited states. IV β-agonist infusions offer no advantage over aerosolized or metered-dose inhaler–delivered agents and carry an increased risk of systemic side effects. Salmeterol xinafoate and formoterol are long-acting β 2-adrenergic agonists that bind with greater affinity to the β 2-receptor site than alb uterol. These are maintenance, not acute, therapy. Bronchodilator effects last at least 12 hours, and tachyphylaxis is undocumented with longterm use. Long-acting β 2-adrenergic agonists are an effective treatment for long-term control of asthma, especially in conjunction with inhaled corticosteroids. Use short-acting β 2-adrenoreceptor agonists (e.g., albuterol) for infrequent or breakthrough symptoms that occur despite the use of long-acting β 2-adrenoreceptor agonists.8-11,24  CORTICOSTEROIDS Corticosteroids produce beneficial effects by restoring β-adrenergic responsiveness and reducing inflammation and are used in all but mild, easily fully reversed episodes of acute asthma. The peak anti-inflammatory effect occurs at least 4 to 8 hours after IV or PO administration. Early use is wise; corticosteroids given within 1 hour of arrival in the ED reduce the need for hospitalization. 26 Although there is disagreement over the optimal dose in acute asthma, an initial dose of PO prednisone of 40 to 60 milligrams or IV methylprednisolone of 1 milligram/kg is sufficient, and higher-dose corticosteroid therapy has no clear advantage.26,27 Give patients who are being discharged home after ED treatment a 5- to 10-day nontapering course of prednisone (40 to 60 milligrams/d in a single daily dose or its equivalent) or a 2-day course of oral dexa methasone (16 milligrams/d in a single daily dose).8-11,28-30 A single dose of depot methylprednisolone, 150 milligrams IM, is another option if compliance is a concern.31 Current recommendations are to use inhaled corticosteroids for all patients with mild persistent asthma or more severe chronic asthma.8-11,32 This means discharging patients with mild persistent or more severe asthma on maintenance inhaled corticosteroids in addition to any systemic bursts.

f compliance is a concern.31 Current recommendations are to use inhaled corticosteroids for all patients with mild persistent asthma or more severe chronic asthma.8-11,32 This means discharging patients with mild persistent or more severe asthma on maintenance inhaled corticosteroids in addition to any systemic bursts. 33-35 Inhaled corticosteroid options are beclomethasone, 80 to 240 micrograms/d; budesonide, 180 to 600 micrograms/d; fluni solide, 500 to 1000 micrograms/d; fluticasone, 88 to 264 micrograms/d; mometasone, 200 micrograms/d; and triamcinolone acetonide, 300 to 750 micrograms/d.  ANTICHOLINERGICS Anticholinergics are additive therapy to β-adrenergic agents in ED patients with acute asthma. Anticholinergics affect large, central air ways, whereas β-adrenergic drugs dilate smaller airways. The anticholinergic commonly used is inhaled ipratropium bro mide, available as a nebulized solution and a metered-dose inhaler or in combination with albuterol 8-11 (Table 69-5). Use an aerosolized ipratropium bromide solution, 0.5 milligram, in ED patients with moderate to severe exacerbation. 8-11 Adding multiple doses of ipratropium bromide to a short-acting selective β-agonist may improve bronchodilation and decrease the rate of hospitalization among patients with moderate-to-severe acute asthma, 36 although this benefit is not universal. 37 Potential side effects with anticholin ergics include dry mouth, tachycardia, restlessness, irritability, confu sion, difficulty in micturition, ileus, blurring of vision, and an increase in intraocular pressure. Long-acting anticholinergic agents have no role in acute asthma care. FOLLOW-UP OF PATIENTS WITH ACUTE ASTHMA Disposition decisions should take into account a combination of subjective parameters, such as resolution of wheezing and improvement in air exchange, as assessed by auscultation and patient opinion; objective measures, such as normalization of PEFR; and historical factors, such as compliance, history of ED use, and hospitalization. Some degree of residual airflow obstruction, airway lability, and inflammation persists after treatment and discharge from the ED. Advise discharged patients to use a short-acting β-agonist on a scheduled basis for several days and to complete any oral corticosteroid regimens. Start inhaled corticosteroids in patients with a history of per sistent asthma not already using this regimen. 33-35 A good response to treatment resolves symptoms and results in PEFR of >70% predicted; these patients can be safely discharged home. Patients with a poor response to treatment have persistent symptoms and FEV 1 or PEFR of <40% predicted; these patients are usually best observed or hospitalized. An incomplete response to treatment, the middle ground, commonly has some persistence of symptoms and FEV 1 or PEFR between 40% and 69% predicted. Most patients with asthma treated in the ED fall into this category and may be discharged home safely, although some benefit from prolonged observation or hospitalization 8-11 (Table 69-2). Patients who fail to improve adequately over a period of several hours because they are in the late phase of their exacerbation and those with significant risk factors for death from acute asthma are best placed in an observation unit or hospital bed. Many patients can be successfully treated in an ED observation unit with evidence-based care protocols. Arrange follow-up care by primary care physician or asthma specialist (within 1 to 4 weeks) to ensure resolution and to review the long-term medication plan for the chronic management of asthma. 8-11 Deliver an appropriate written discharge plan of action that addresses routine care and care of worsening symptoms ( Table 69-6).

ollow-up care by primary care physician or asthma specialist (within 1 to 4 weeks) to ensure resolution and to review the long-term medication plan for the chronic management of asthma. 8-11 Deliver an appropriate written discharge plan of action that addresses routine care and care of worsening symptoms ( Table 69-6). Educate patients on asthma triggers (including smoking cessation education if indicated), and review all discharge medications and the correct use of the inhaler and a peak flow meter (for daily tracking). STATUS ASTHMATICUS (ACUTE SEVERE ASTHMA) Status asthmaticus is an acute severe asthma that does not improve with usual doses of inhaled bronchodilators and corticosteroids. Find ings include hypoxemia, tachypnea, tachycardia, accessory muscle use, and wheezing (although this may be absent when airflow is severely reduced). Rapid and aggressive bronchodilator treatment is the key to preventing cardiopulmonary arrest. In addition to bronchodilators and early corticosteroids, other treatment adjuncts are often necessary.  MAGNESIUM IV magnesium sulfate can aid the management of acute, very severe asthma (FEV 1 or PEFR of <25% predicted). 39 The magnesium dose is 1 to 2 grams IV over 30 minutes. Nebulized magnesium is effective and may improve pulmonary function in severe acute asthma when it follows aggressive β-agonist and corticosteroid therapy. 39-41 Dosing regimens vary; one regimen is 95 milligrams of nebulized magnesium sulfate in four divided doses 20 minutes apart, and another is 384 milligrams of nebulized magnesium sulfate in sterile water. When using magnesium in any form, monitor blood pressure and deep tendon reflexes during administration 42 because hypotension or neuromuscular blockade may occur, although this is exception ally rare in the doses recommended. Tintinalli_Sec08_p0425-0472.indd 465 8/1/19 2:10 PM

lized magnesium sulfate in sterile water. When using magnesium in any form, monitor blood pressure and deep tendon reflexes during administration 42 because hypotension or neuromuscular blockade may occur, although this is exception ally rare in the doses recommended. Tintinalli_Sec08_p0425-0472.indd 465 8/1/19 2:10 PM 466 SECTION 8: Pulmonary Disorders  NONINVASIVE POSITIVE-PRESSURE VENTILATION Noninvasive positive-pressure ventilation (see Chapter 28, “Noninvasive Airway Management and Supraglottic Airways”) improves airflow and respirations compared with usual care. Despite little research, it is commonly used in clinical practice for status asthmaticus. 43,44 Noninvasive positive-pressure ventilation may decrease the need for tracheal intubation and result in clinical improvement. 44 Do not institute noninvasive positive-pressure ventilation when altered sensorium or near respiratory collapse exists; those situations require intubation. Exclude pneumothorax before beginning noninvasive positive-pressure ventilation.  KETAMINE Ketamine inhibits reuptake of noradrenaline and increases circulating catecholamines, aiding some with severe acute asthma. An IV bolus dose of 0.15 milligram/kg followed by an infusion of 0.25 milligram/ kg/h is sometimes used. 45 If intubation is needed, ketamine is a pre medication and/or sedative agent to aid during the procedure and after mechanical ventilation starts. There are limited controlled trial data on ketamine and outcomes in treating severe acute asthma. TABLE 69-6 Checklist for ED Discharge in Patients With Acute Asthma Intervention Dose/Timing Education/Advice MD/RN Initials Inhaled medications (e.g., MDI with valved holding chamber; nebulizer) Select agent, dose, and frequency (e.g., albuterol). Teach purpose. Short-acting β 2-agonist 2–6 puffs every 4 h until symptoms completely resolve. Teach and check technique. Corticosteroids Low to medium dose for patients with chronic persistent asthma. For MDIs, emphasize the importance of using a spacing device or holding chamber. Oral medications Select agent, dose, and frequency (e.g., prednisone 40 milligrams once a day for 5 d). Teach purpose. Teach side effects. Peak flow meter For selected patients: measure a.m. and p.m. peak expiratory flow, and record best of 3 tries each time. Teach purpose. Teach technique. Distribute peak flow diary.

Corticosteroids Low to medium dose for patients with chronic persistent asthma. For MDIs, emphasize the importance of using a spacing device or holding chamber. Oral medications Select agent, dose, and frequency (e.g., prednisone 40 milligrams once a day for 5 d). Teach purpose. Teach side effects. Peak flow meter For selected patients: measure a.m. and p.m. peak expiratory flow, and record best of 3 tries each time. Teach purpose. Teach technique. Distribute peak flow diary. Follow-up visit If possible, make appointment for follow-up care with primary clinician or asthma specialist or advise patient to make appointment in 1–4 wk. Advise patient (or caregiver) of date, time, and location of appointment, ideally within 7 d of hospital discharge. Action plan Before or at discharge. Instruct patient (or caregiver) on simple plan for actions to be taken when symptoms, signs, and peak expiratory flow values suggest recurrent airflow obstruction.

Follow-up visit If possible, make appointment for follow-up care with primary clinician or asthma specialist or advise patient to make appointment in 1–4 wk. Advise patient (or caregiver) of date, time, and location of appointment, ideally within 7 d of hospital discharge. Action plan Before or at discharge. Instruct patient (or caregiver) on simple plan for actions to be taken when symptoms, signs, and peak expiratory flow values suggest recurrent airflow obstruction. Abbreviations: MD = physician; MDI = metered-dose inhaler; RN = nurse. Sources: National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services.  EPINEPHRINE Although epinephrine is standard treatment for anaphylactic asthma, it is an adjunct to treat status asthmaticus. Give epinephrine SC or IM, 0.5 milligram, in adults (standard adult EpiPen ® dose) for refractory situations.11  MECHANICAL VENTILATION If the patient manifests progressive hypercarbia or acidosis or becomes exhausted or confused, intubation and mechanical ventilation (see Chapter 29A and 29B, “Tracheal Intubation and Mechanical Ventilation”) are necessary to prevent respiratory arrest. Mechanical ventilation does not relieve the airflow obstruction—it merely reduces the work of breathing and enables the patient to rest while the airflow obstruction is resolved. The potential complications of mechanical ventilation in patients with acute asthma include high peak airway pressures with subsequent barotrauma and hemodynamic impairment (e.g., decreased preload). Mucous plugging is frequent, leading to increased airway resistance, atelectasis, and obstructive pneumonia. Due to the severity of airflow obstruction during the early phases of treatment, the tidal volume may be larger than the returned volume, leading to air trapping and increased residual volume (intrinsic positive end-expiratory pressure). Using rapid inspiratory flow rates at a reduced respiratory frequency (12 to 14 breaths/min) and allowing adequate time for the expiratory phase can mitigate these effects. Also, it is reasonable to target adequate arterial oxygen saturation (≥90%) without concern for “normalizing” the hypercarbic acidosis. This approach is called controlled mechanical hypoventilation or permissive hypoventilation. Ventilation of patients with acute asthma requires sedation. Neuromuscular blocking agents may be required, but extended use may cause postextubation muscle weakness.  AGENTS OF UNCERTAIN OR NO BENEFIT IN STATUS ASTHMATICUS Heliox A mixture of 80% helium and 20% oxygen (heliox) can lower airway resistance and aid treatment of severe acute asthma. 47 Although there is no role for this intervention in routine care, it is an option for patients who do not respond to standard therapy. 8,48 Methylxanthines Aminophylline (5 milligrams/kg IV over 20 min utes) is no longer a first- or second-line treatment for acute asthma. 49 The most common side effects of methylxanthines are tachycardia, nervousness, nausea, vomiting, anorexia, and headache. At plasma levels >30 milligrams/mL, there is a risk of seizures and cardiac dysrhythmias. Other Agents Mast cell modifiers, such as cromolyn and nedocromil, exert their anti-inflammatory action by blockage of chlorine channels, modulating mast cell mediator release and eosinophil recruitment. These agents inhibit early and late responses to allergen challenge and exercise. Neither is indicated for treatment of acute bronchospasm. Leukotrienes are potent proinflammatory mediators that contract airway smooth muscle, increase microvascular permeability, stimulate mucus secretion, decrease mucociliary clearance, and recruit eosino phils into the airway. Several leukotriene modifiers, such as montelukast, zafirlukast, and zileuton, are available as oral medications for the treatment of asthma.

tors that contract airway smooth muscle, increase microvascular permeability, stimulate mucus secretion, decrease mucociliary clearance, and recruit eosino phils into the airway. Several leukotriene modifiers, such as montelukast, zafirlukast, and zileuton, are available as oral medications for the treatment of asthma. Leukotriene modifiers improve lung function, diminish symptoms, and diminish the need for short-acting β 2-agonists. They may be used as an alternative to low-dose inhaled corticosteroid therapy in mild persistent asthma and as steroid-sparing agents with inhaled corticosteroids in moderate persistent asthma. 7-10 Despite tri als with adjuvant IV montelukast for acute asthma, 50,51 there is limited evidence to support a role for PO or IV leukotriene modifiers in acute asthma management. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Tintinalli_Sec08_p0425-0472.indd 466 8/1/19 2:10 PM