AUTHOR INFORMATION

Section 1 of 11

Authored by Carlos A Camargo, Jr, MD, DrPH, Director, EMNet Coordinating Center, Associate Professor of Medicine & Epidemiology, Harvard Medical School, Department of Emergency Medicine, Massachusetts General Hospital

Coauthored by Barry Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, and Professor of Anatomy and Neurobiology, Research Director, Department of Emergency Medicine, University of Arkansas for Medical Sciences

Carlos A Camargo, Jr, MD, DrPH, is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Emergency Physicians, American College of Epidemiology, American College of Physicians, American Heart Association, American Medical Association, American Public Health Association, American Thoracic Society, Massachusetts Medical Society, Society for Academic Emergency Medicine, and Society for Epidemiologic Research

Edited by Edward Bessman, MD, Chairman, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Paul Blackburn, DO, Program Director, Department of Emergency Medicine, Maricopa Medical Center; Assistant Professor, Department of Surgery, University of Arizona; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Author's Email:	Carlos A Camargo, Jr, MD, DrPH
Editor's Email:	Edward Bessman, MD

eMedicine Journal, August 1 2006, VOLUME 7, Number 8

INTRODUCTION

Section 2 of 11

Background: Asthma is a common disorder that accounts for almost 2 million ED visits each year in the United States. On average, this represents approximately 2% of all ED visits. In urban centers, however, acute asthma may comprise up to 10% of all ED visits.

Pathophysiology: Asthma is a condition characterized by paroxysmal narrowing of the bronchial airways due to inflammation of the bronchi and contraction of the bronchial smooth muscle. The inflammatory component is central to the pathogenesis of symptoms: dyspnea, cough, and wheezing.

Another important mechanism underlying acute asthma involves antigen-antibody interactions, which activate membrane phospholipase and result in production of arachidonic acid. Arachidonic acid is metabolized by cyclooxygenase to vasoactive prostaglandins (eg, thromboxanes, prostacyclins) or leukotrienes and their precursors. Several are potent smooth muscle contractors that produce airway hyperresponsiveness and inflammation. The pharmacologic inhibition of leukotriene synthesis and/or action has a beneficial effect on induced and spontaneous asthma, demonstrating that leukotrienes can be important mediators of acute asthma and reactive airway disease (RAD).

Aspirin, a cyclooxygenase inhibitor, produces severe bronchospasm in sensitive individuals. Leukotriene inhibitors reverse this sensitivity, providing further evidence that leukotrienes are important mediators of asthma.

A balance between the adrenergic and cholinergic systems controls bronchomotor tone. Beta-agonist stimulation induces bronchodilation, and beta-blockers cause bronchoconstriction. More specific beta2-agonists have been developed to avoid the tachycardia associated with nonspecific beta-agonist agents. Cholinergic stimulation may cause bronchoconstriction. Anticholinergic agents (eg, ipratropium) produce bronchodilation.

The airway narrowing in acute asthma manifests itself most commonly in adults as wheezing; in children, nocturnal cough is a very common presentation. The initial component is generally rapidly reversible bronchospasm of the smooth muscles that develops into more refractory inflammation of the airways characterized by bronchial edema, tenacious viscid secretions, mucous plugging, and atelectasis. Common causes of acute asthma include viral upper respiratory infections; exposure to allergens (eg, dustmites, animal dander); smoke inhalation; and cold, dry weather. A strong association had been thought to exist in women between the perimenstrual phase of their cycle and asthma symptoms, but the latest data suggest a more complex association between female sex hormones and asthma.

Frequency:

• In the US: Incidence of acute asthma, defined as the number of persons who develop asthma within a specific time period, is approximately 0.2-0.4% annually. Childhood asthma persists into adulthood in approximately 50% of cases. Those with symptoms persisting into the second decade of life usually have asthma throughout adulthood. Asthma prevalence is 6-10% (ie, 20-25 million persons); one half of these cases are children (ie, 8-20% of all children).

• Internationally: Asthma prevalence varies from 1-30% across nations; the prevalence increases with increased urbanization and affluence. Over the past decade, asthma mortality has been stable in many countries, including Australia, Israel, New Zealand, and the United Kingdom.

Mortality/Morbidity: The death rate from acute asthma increased from 13 deaths per million in 1982 to 19 deaths per million in 1991. Since the early 1990s, however, US asthma mortality rates have been on the decline. Approximately 4,500 Americans die from asthma each year.

Race: Prevalence of asthma in African American and Puerto Rican Hispanic populations is higher than that in Caucasians. The lower average socioeconomic condition of these groups helps to explain the increased prevalence; however, in other countries, asthma is associated with affluence.

Sex: In children younger than 10 years, the male-to-female ratio is 2:1. Between the ages of 18 and 54 years, the ratio is reversed, with women being affected twice as often as men. Women visit the ED and are hospitalized for acute asthma twice as often as men. Previous data suggested that 40% of these hospitalizations occur during the premenstrual phase of the cycle; more recent data from larger studies have not borne out these initial findings. Indeed, some studies suggest a peak in asthma exacerbations shortly before ovulation, when estrogen levels are rising (and not falling).

Age: Asthma symptoms usually begin in early childhood (eg, 80-90% experience symptoms by age 6 y); however, asthma can present at any age, including elderly persons. Children younger than 10 years constitute approximately 50% of all cases.

CLINICAL

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History: Specific historical factors are key in the assessment of acute asthma. The patient should be asked about the following aspects of their disease to help gauge the severity of this episode.

• Precipitating factors may include the following:

• Viral upper respiratory infection

• Allergen exposure (dustmite, animal dander, mold)

• Smoke inhalation

• Change in weather

• Current medications and compliance (eg, frequency of inhaled beta-agonist treatments, use and dose of inhaled corticosteroids)

• Past asthma-related healthcare utilization, including both the frequency of events in last 12 months and the length of time since most recent event:

• Systemic corticosteroids for an asthma exacerbation

• ED visits for asthma exacerbation

• Overnight hospitalization or other admissions for asthma exacerbation

• ICU admission for severe asthma exacerbation

• Endotracheal intubation

• Duration of present symptoms (eg, hours to days): Duration of more than 2 days is associated with a higher admission rate than duration of less than 2 days. Sudden-onset exacerbations (ie, < 3 hours since symptom onset) tend to be more severe but also tend respond better to treatment in the ED and an inpatient setting.

• Degree of dyspnea, cough, wheezing; whether new productive cough is present

• Ask about a patient’s baseline peak flow or personal best peak flow. Many patients know these values, and they can serve as a comparison against current peak flow and help set a goal for improvement in the ED.

• The clinician should address whether the condition is truly asthma. Many other causes of dyspnea, cough, and wheezing exist and include the following:

• Chronic obstructive pulmonary disease (COPD), which usually requires smoking more than 20 pack-years of cigarette smoking

• Bronchopulmonary dysplasia, cystic fibrosis, sarcoidosis, or other pulmonary disease

• History of heart disease (cardiac asthma)

• Presence of chest pain or pleuritis, which may suggest a complication of more severe exacerbations

Physical:

• Level of alertness

• Ability to lie flat: Patients with mild acute asthma are able to lie flat. In more severe cases, the patient assumes a sitting position. As the severity increases, the patient increasingly assumes a hunched-over sitting position with the hands supporting the torso, termed the tripod position. If symptomatology becomes more severe, profuse diaphoresis occurs. The diaphoresis presents concomitantly with a rise in PCO₂ and hypoventilation. In the most severe form of acute asthma, the patient may struggle for air and/or be bradypneic and be profusely diaphoretic; almost no breath sounds may be heard, and the patient is willing to lie recumbent.

• Ability to speak/staccato speech

• Stridor

• Accessory muscle use - In children, also look for supraclavicular and intercostal retractions and nasal flaring as well as abdominal breathing.

• Central cyanosis

• Peripheral edema

• Subcutaneous emphysema

• Bilateral breath sounds

• Wheezing: Inspiration-expiration ratio reveals prolongation of the expiratory phase (eg, 1:1 mild, 1:3 severe). Wheezing may be absent both during a severe presentation with very poor air exchange or in mild exacerbations. In a situation with mild exacerbation, request rapid forced expiration to see if a wheeze becomes audible.

• Peak flow measurements: A peak flow value should be obtained early in the course of the ED visit to document severity as well as to serve as a baseline against which improvement may be measured.

Causes:

• Respiratory infections (most common reason for exacerbations)

• Allergen exposure, particularly cats

• Exercise

• Weather, including cold and dry air, weather changes, significant increases in humidity

• Air pollution

• Aspirin ingestion

• Yellow dyes, particularly tartrazine, found in yellow gelatins

• Organic particle exposure, including the following:

• Cotton (byssinosis)

• Detergent manufacture (Bacillus subtilis)

• Red cedar

• Grains

• Chemical irritants (ie, toluene diisocyanate) may be related to nocturnal asthma.

• The worst bronchospasm is usually at about 4 am, and the best airflow is at approximately 4 pm; therefore, asthma control is labile. The explanation for this circadian pattern is not clear, but it involves factors beyond acid reflux, sinusitis, or postnasal dripping during sleep. Nonetheless, all of these nocturnal factors can worsen asthma status.

DIFFERENTIALS

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Chronic Obstructive Pulmonary Disease and Emphysema

Other Problems to be Considered:

Anaphylaxis (adult, pediatric)
Bronchiolitis (pediatric)
Foreign body ingestion (pediatric, adult incompetent, neurologically impaired)
Polyarteritis nodosa
Adrenal insufficiency if steroids stopped too abruptly
Congestive heart failure and myocarditis
Pulmonary embolism (especially multiple)
Upper airway disease
Panic disorder and hyperventilation syndrome
Pneumonia, bronchitis

WORKUP

Section 5 of 11

Lab Studies:

• Laboratory studies are not indicated for most ED patients with acute asthma, and they should not delay treatment for someone in respiratory distress.

• The white blood cell (WBC) count may be elevated if the patient is taking prednisone, has received catecholamines (ie, epinephrine), or has been under significant stress.

• Eosinophilia may be helpful in diagnosing asthma in a patient with new-onset wheezing and bronchospasm reversible with beta2-agonists.

• Although potassium may be diminished with beta2-agonist treatment, this hypokalemia rarely produces any clinically significant effects.

• Serum theophylline levels are helpful in monitoring patient compliance and excluding inadvertent theophylline toxicity.

• Arterial blood gas

• Arterial blood gas (ABG) measurement provides important information in acute asthma. This test may reveal dangerous levels of hypoxemia or hypercarbia secondary to hypoventilation; typically, results are consistent with respiratory alkalosis.

• Because of the accuracy and utility of pulse oximetry, only patients whose oxygenation is not restored to over 90% with oxygen therapy require an ABG. The clinical picture usually obviates ABGs for most ED patients with acute asthma.

• Venous levels of PCO₂ have been tested as a substitute for arterial measurements, and a venous PCO₂ of >45 mm may serve as a screening test but cannot substitute for the ABG evaluation of respiratory function.

• Hypercarbia is of concern in that it reflects inadequate ventilation and may indicate the need for mechanical ventilation if the PCO₂ is elevated as a result of patient exhaustion; however, the decision to proceed with endotracheal intubation and mechanical ventilation is a clinical assessment.

Imaging Studies:

• Chest radiography

• Chest radiography of patients with acute asthma rarely reveals clinically significant findings, although it may show streaky infiltrates or hyperinflation of the lung fields. It may be helpful in suggesting the diagnosis of asthma in the ED or in unclear causes of dyspnea.

• Patients with pleuritic chest pain require a chest film to exclude pneumothorax or pneumomediastinum, particularly if subcutaneous emphysema is present.

• Chest radiography is indicated in those with fever to rule out pneumonia. Acute sinusitis may exacerbate asthma, and sinus radiograph results are frequently positive in patients who have acute asthma and a fever. However, the nonspecificity of sinus films should temper enthusiasm for this imaging study.

• With new-onset asthma and eosinophilia, a radiograph may be useful in identifying prominent streaky infiltrates persisting less than 1 month, indicating Loeffler pneumonia. The infiltrates of Loeffler pneumonia are peripheral with central sparing of the lung fields. These findings have been described as the radiographic negative of pulmonary edema.

Other Tests:

• Electrocardiogram and ECG monitoring

• Patients with asthma who are severely symptomatic should have ECG monitoring, as with any seriously ill patient.

• Sinus tachycardia and ECG evidence of right heart strain are common in patients with acute asthma. The use of beta2-agonist therapy will cause a paradoxical decrease in heart rate as pulmonary function improves and symptoms are relieved.

• Supraventricular tachycardia raises the consideration of theophylline toxicity.

• Arrhythmias, other than supraventricular tachycardia, are rare.

• Pulse oximetry

• Pulse oximetry measurement is desirable in all patients with acute asthma to exclude hypoxemia. The hypoxemia of uncomplicated acute asthma is readily reversible by oxygen administration. Oxygenation decreases 4-10 mm Hg with beta-agonist inhalant therapy due to increases in V/Q mismatch. Therefore, all patients with acute asthma should have oxygen saturation measured by pulse oximetry, or they simply should be placed on oxygen therapy.

• In children, pulse oximetry is often used to grade severity of acute asthma. Oxygen saturation of 97% or above constitutes mild asthma, 92-97% constitutes moderate asthma, and less than 92% signifies severe asthma. Although an isolated pulse oximetry reading at triage is not predictive in most cases (with the notable exception of severe attacks that usually are self-evident on visual inspection), serial monitoring of pulse oximetry status can provide more subtle evidence for or against the need for hospital admission.

• Spirometry provides a physiologic assessment of airflow and degree of bronchospasm. It gives a more objective assessment of the level of bronchospasm than subjective findings of dyspnea and degree of wheezing. Although valuable in adults, obtaining accurate values in the emergency setting is often difficult (or impossible) among most children younger than 6 years.

• Peak expiratory flow (PEF) measurement is common in the ED because it is inexpensive and portable. Serial measurements document response to therapy and, along with other parameters, are helpful in determining whether to admit the patient to the hospital or discharge from the ED. A limitation of PEF is that it is dependent on effort by the patient. Forced expiratory volume in one second (FEV1) is also effort dependent but less so than PEF. FEV1 is not often used in the ED except in research settings.

• PEF in the ED can be compared with asymptomatic (baseline) PEF, if known. Unfortunately, patients often do not know their asymptomatic PEF. Moreover, the reference group for the ideal PEF percent predicted (based on age, sex, height) may not be accurate for the patient population seen in many inner city EDs since most equations are based on white populations.

TREATMENT

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Prehospital Care: Therapy for acute asthma can be initiated in the prehospital setting consistent with EMS providers’ legally authorized scope of practice and local medical direction. The primary treatment approach is administration of supplemental oxygen and inhaled bronchodilators. The latter treatment most often involves inhaled beta2-agonists given by hand-held nebulizer or using a metered-dose inhaler (MDI) with spacer (holding chamber). If these delivery devices are not available, subcutaneous epinephrine or terbutaline can be given for severe exacerbations.

When initiating bronchodilator use, EMS personnel should not delay patient transport to the appropriate medical facility—which remains a high priority. If necessary, and again consistent with the scope of practice and local medical direction, bronchodilator treatments may be repeated while transporting patients. Prolonged transport times (eg, in rural settings or during transport on congested urban streets) may necessitate multiple bronchodilator treatments before arrival to the medical facility. To improve prehospital care, ambulance services are encouraged to develop protocols for the management of acute asthma in children and adults. Recently, a model protocol was developed by a CDC-funded workgroup to help advance this process.

Emergency Department Care:

• The mainstay of ED therapy for acute asthma is inhaled beta2-agonists. The most effective particle sizes are 1-5 mm. Larger particles are ineffective because they are deposited in the mouth and central airways. Particles smaller than 1 mm are too small to be effective since they move in the airways by Brownian motion and do not reach the lower airways.

• Standard delivery systems and routes are as follows:

• Albuterol 2.5-5 mg every 20 minutes for 3 doses, then 2.5-10 mg every 1-4 hours as needed. Dilution of 2.5 mg in 3-4 mL of saline or use of premixed nebules is standard. Oxygen or compressed air delivery of the inhaled beta-agonists should be at a rate of 6-8 L/min. For children, use 0.15 mg/kg (minimum dose 2.5 mg) every 20 minutes for 3 doses then 0.15-0.3 mg/kg up to 10 mg every 1-4 hours as needed.

• An equivalent method of beta-agonist delivery in mild-to-moderate exacerbations is the MDI used in conjunction with a spacer or holding chamber. For severe exacerbations, it is less clear if nebulized versus MDI/spacer delivery is truly equivalent. Each puff delivers a standard 90 mcg of albuterol. The dose is 4-8 puffs every 20 minutes up to 4 hours, then every 1-4 hours as needed. A potential advantage of the MDI/holding chamber is that it requires little or no assistance from the respiratory therapist once the patient understand how to use administer the medication; the patient can be discharged from the ED with the same spacer and albuterol canister. This modality is especially effective in areas where patients may be unable to afford their inhaled beta-agonists.

• Continuous nebulization may be superior to the MDI/holding chamber method in a patient with severe exacerbations (eg, PEF <200 L/min). The dose of albuterol is 10-15 mg in 70 mL of isotonic saline. For children, this method is reserved for severe asthma at an albuterol dose of 0.5 mg/kg/h. Based on meta-analyses, there is no advantage of intravenous albuterol over inhaled albuterol, even in severe asthma. However, the role of parenteral beta-agonists in addition to inhaled beta-agonist treatments is uncertain.

• Side effects may include tremor and a slight tendency toward tachycardia. However, many patients who present with acute asthma and tachycardia actually decrease their heart rate with inhaled beta-agonist therapy. Also, inhaled beta-agonists decrease potassium by an average of 0.4 mEq/L.

• Patients who respond poorly or not at all to an inhaled beta-agonist regimen may respond to parenteral beta 2-agonists, such as 0.25 mg terbutaline or 0.3 mg of 1:1000 concentration of epinephrine administered subcutaneously. This treatment should be reserved for patients who are seriously ill and not responding to serial treatments with inhaled beta-agonist/anticholinergic therapy and other more established therapies.

• Ipratropium 0.5 mg has had variable benefit in controlled trials demonstrating most consistent efficacy in children and smokers with comorbid COPD. The 1997 and 2002 NAEPP guidelines recommend its use in severe exacerbations only. Ipratropium should be given in combination with albuterol every 20 minutes for 3 doses then as needed. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized.

• For severe asthma exacerbations, intravenous magnesium sulfate has been shown to be beneficial. The usual dose is 2 g over 20 minutes; the effect of higher and faster doses is uncertain. These larger doses have demonstrated safety for almost 50 years in the obstetrics literature, with rates as high as 1 g/min for 3 g. Intravenous magnesium sulfate has little (if any) value in mild-to-moderate exacerbations and should not be used in that setting.

• Research studies suggest that inhaled corticosteroids may one day have a role in the management of acute asthma, in addition to the important role they play in preventing exacerbations in the first place. Data are limited, but randomized trials suggest that the use of inhaled corticosteroids in the ED can result in improved pulmonary function in approximately 90 minutes and thereby decrease risk of hospital admission. This therapeutic approach is experimental and thought to work through nonspecific vasoconstriction in the airways. The time to pulmonary function benefit (90-120 min) is too short to support an anti-inflammatory effect mediated by the traditional effects of corticosteroids within a cell. The potential role of inhaled corticosteroids in acute asthma remains under investigation.

• Heliox is a helium-oxygen (80:20 or 70:30) mixture that may provide dramatic benefit for ED patients with severe exacerbations.
  • Helium is about 25% as dense as room air and, consequently, it travels more easily down narrowed passages. This property makes heliox of particular value to patients at risk of intubation—by quickly decreasing the work of breathing and, when the gas mixture is used to drive the nebulizer, by better delivery of the inhaled bronchodilator.

  • Despite considerable promise, the literature shows mixed results. Potential explanations include the large number of small trials (low statistical power) and suboptimal delivery of albuterol to the patient. Briefly, heliox-driven nebulizer treatments should have the gas set at a rate of 8-10 L/min and with double the usual amount of albuterol. These adjustments result in the delivery of the appropriate amount of albuterol to the patient but with particles being delivered in the heliox mixture instead of oxygen or room air. When patients need supplemental oxygen, one can deliver it via nasal prong. Of course, as the supplemental oxygen is increased, the benefits of using heliox decrease. Oxygen requirements should determine the ideal mix. The role of heliox in acute asthma remains under investigation.

• Intravenous leukotriene modifiers (such as montelukast 7 mg IV) provide rapid bronchodilation (within 10 min), but they are not yet available outside of phase II/III research trials. Montelukast 10 mg orally may produce an increase in FEV1 in severe asthma exacerbations, but, given the pharmacokinetics of the drug, this benefit may not be seen for approximately 90 minutes. The role of leukotriene modifiers in acute asthma is an active area of research.

• In life-threatening exacerbations, to avoid intubation, many of these therapies (including inhaled albuterol, inhaled ipratropium, intravenous and inhaled corticosteroids, intravenous magnesium sulfate, parenteral terbutaline, heliox, and oral montelukast) may be administered simultaneously. Although the individual contribution of each treatment is uncertain, most of these agents contribute to bronchodilation in different ways, and each likely adds a little to what may be an important overall improvement.

• Despite the best efforts of the ED, some patients will require endotracheal intubation. Approximately 5-10% of all asthma hospitalizations are to an intensive care unit—for further care of already intubated patients or for close supervision of patients at very high risk of intubation. Mechanical ventilation of patients with acute asthma presents special challenges, such as the risk of high pressures lowering systemic blood pressure (auto-PEEP) and less commonly, complications such as barotrauma, pneumothorax, or pneumomediastinum. The role of permissive hypercapnia goes beyond the scope of this article but is a ventilator strategy used in the ICU management of some patients with severe asthma exacerbations.

• In general, 3-4 hours in the ED is adequate time to determine if a patient with acute asthma has improved symptomatically and demonstrates pulmonary flow rates sufficiently improved for safe discharge. To allow time for corticosteroids to take effect, extended treatment in a clinical holding area has been demonstrated to be effective. Such observation units have avoided 60% of admissions to the hospital for acute asthma by treating and observing the patient for as long as 12 hours. These units are appropriate if nursing care and monitoring are adequate. They provide an excellent site for specialized asthma education.

• In one holding unit, asthma study patients were discharged within 12 hours at 50% of predicted PEF if they had no high-risk relapse factors (see list above) or at 60% of predicted PEF if they had one or more high-risk relapse factors. At time of discharge, patients were given albuterol inhalers and prednisone tablets, avoiding delay and inconvenience of filling the prescriptions and possible noncompliance. At 2 weeks following the ED visit, a 9% relapse rate was noted, considerably less than the 20% for most EDs.

• Inability to obtain medications due to socioeconomic factors should lower the threshold for hospital admission for patients who have asthma and PEF of 50-69% of predicted or personal best.

MEDICATION

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The goals of therapy are to maintain SaO₂ greater than 92% and to treat dehydration only if it is clinically apparent. Routine hydration is not indicated.

Antibiotics should be administered only if bacterial sinusitis, bronchitis, or pneumonia is suspected clinically. Asthma exacerbation severity and therapeutic choices instituted should be evaluated according to the percent of predicted FEV1 or PEF. The 2002 National Asthma Education and Prevention Program (NAEPP) cutpoints are less than 50% (severe exacerbation), 50-79% (moderate exacerbation), and 80% or higher (mild exacerbation). Some experts believe that more appropriate cutpoints are less than 40% as “severe” (because that is the approximate percentage predicted where several adjunct therapies, such as continuous nebulization and intravenous magnesium, begin to work) and 70% or higher as “mild” (because that is the target PEF for discharge of patients from the ED).

Drug Category: Corticosteroids -- These anti-inflammatory agents have myriad effects, including restoration of beta2-agonist receptors in the bronchial smooth muscles and, therefore, improved response to beta2-agonists.

Corticosteroids are indicated in all patients with severe exacerbations and in the vast majority of patients with moderate exacerbations. If response to the first or second beta2-agonist inhaler treatment is incomplete, this too is an indication for corticosteroids in most patients.

Additional high-risk patients for whom corticosteroids may be recommended are those who require frequent ED visits, have been admitted with asthma exacerbations, have been intubated, are already on outpatient steroids, or have been experiencing an episode for longer than 2-3 days.

The onset of action of corticosteroids is approximately 4-6 hours. The bioavailability of orally and parenterally administered steroids is the same, and numerous randomized double-blind trials have demonstrated this equivalence. A primary reason to use intravenous corticosteroids is the adage to avoid medications by mouth when intubation is imminent. However, for most ED patients with acute asthma, the use of oral corticosteroids obviates placement of an intravenous line.

Drug Name	Prednisone (Deltasone, Orasone, Meticorten) -- Useful in treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.
Adult Dose	40-60 mg PO (often administered once in ED in place of IV/IM corticosteroids) followed by discharge from hospital with 40-50 mg/d for 5-10 d; 50-mg tab provides a very convenient and effective prescription: 1 tab, once daily for 5 d
Pediatric Dose	1-2 mg/kg PO qd (maximum 60 mg/d) for 3-10 d
Contraindications	Documented hypersensitivity; viral, fungal, connective tissue, or tubercular skin infections; peptic ulcer disease; hepatic dysfunction; GI disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation after >10 d of corticosteroid treatment may cause adrenal crisis; adverse effects include hyperglycemia, edema, myopathy, hypokalemia, euphoria, psychosis, myasthenia gravis, and infections

Drug Name	Methylprednisolone (Solu-Medrol, Depo-Medrol) -- For treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. Depo-Medrol is long-lasting and avoids compliance problems and financial issues that may affect patients' ability to obtain outpatient corticosteroids.
Adult Dose	80-125 mg IV, then 40-80 mg IV in 1 or 2 divided doses until PEF reaches 70% of predicted or personal best
Pediatric Dose	2 mg/kg IV, then 1 mg/kg/dose IV in 2 divided doses (maximum 60 mg/d) until PEF 70% of predicted or personal best
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia if taking concurrent diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hyperglycemia, edema, hypokalemia, euphoria, psychosis, myopathy, and infections are possible complications

Drug Name	Triamcinolone (Aristocort) -- Decreases inflammation by suppressing migration of PMNs and reversing capillary permeability.
Adult Dose	60 mg IM, followed by additional doses of 20-100 mg IM; doses given when signs and symptoms recur
Pediatric Dose	<6 years: Not recommended 6-12 years: 0.03-0.2 mg/kg IM at 1- to 7-d intervals >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; fungal, viral, and bacterial skin infections
Interactions	Coadministration with barbiturates, phenytoin, or rifampin decreases effects
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Multiple complications (eg, severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression) may occur; abrupt discontinuation after >10 d of corticosteroid treatment may cause adrenal crisis

Drug Category: Bronchodilators -- Their primary action is to decrease muscle tone in both small and large airways in lungs, thus increasing airflow and ventilation. This category includes beta-adrenergic, methylxanthine, and anticholinergic medications.

Drug Name	Albuterol (Proventil, Ventolin) -- Bronchodilator in reversible airway obstruction due to asthma. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on heart rate.
Adult Dose	2.5-5 mg q20min for 3 doses, then 2.5-10 mg q1-4h prn; dilute 2.5 mg in 3-4 mL of saline or use premixed nebules
Pediatric Dose	0.15 mg/kg (minimum dose 2.5 mg) q20min for 3 doses, then 0.15-0.3 mg/kg up to 10 mg q1-4h prn
Contraindications	Documented hypersensitivity
Interactions	Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, or sympathomimetic agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism; excessive use may result in tolerance and hypokalemia and hypomagnesemia; adverse reactions may occur more frequently in children aged 2-5 y

Drug Name	Epinephrine (EpiPen, TwinJect) -- Alpha-agonist effects increase peripheral vascular resistance and reverse peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta-agonist activity of epinephrine produces bronchodilatation. IM route (outer thigh) probably provides faster and more consistent epinephrine delivery than SC route.
Adult Dose	0.3-0.5 mg IM q20min for up to 3 doses.
Pediatric Dose	0.01 mg/kg up to 0.3-0.5 mg IM q20min for up to 3 doses
Contraindications	Documented hypersensitivity; cardiac arrhythmias; angle-closure glaucoma; use as local anesthetic in areas such as fingers or toes (vasoconstriction may produce sloughing of tissue); use during pregnancy (decreases uterine blood flow causing uteroplacental insufficiency)
Interactions	Increases toxicity of halogenated inhalational anesthetics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias; caution in elderly persons and hyperthyroidism

Drug Name	Terbutaline (Brethaire, Bricanyl) -- Selective beta2-agonist acts directly on beta2-receptors, relaxing bronchial smooth muscle, relieving bronchospasm, and reducing airway resistance.
Adult Dose	0.25 mg SC q20min for up to 3 doses 2 puffs MDI q4-6h 5 mg PO tid; not to exceed 15 mg/d
Pediatric Dose	<12 years: 0.25 mg SC q20min for up to 3 doses; 2 puffs MDI q4-6h; 0.05 mg/kg/dose PO tid, not to exceed 5 mg/d >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; tachycardia resulting from cardiac arrhythmias
Interactions	Concomitant beta-blockers may inhibit bronchodilating, cardiac, and vasodilating effects of beta-agonists; concomitant MAOIs may result in hypertensive crisis; concurrent oxytocic drugs such as ergonovine may result in severe hypotension
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Through intracellular shunting, terbutaline may decrease serum potassium levels, which can produce adverse cardiovascular effects; decrease is usually transient and may not require supplementation

Drug Name	Ipratropium (Atrovent) -- Anticholinergic agent with antisecretory properties. When applied locally, inhibits secretions from serous and seromucous glands lining nasal mucosa. Ipratropium has been found effective in severe asthma exacerbations only. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized.
Adult Dose	Nebulizer: 0.5 mg q20min for 3 doses then prn MDI: 8 puffs q20min prn up to 3 h
Pediatric Dose	Nebulizer: 0.25-5 mg q20min for 3 doses, then prn MDI: 4-8 puffs q20min up to 3 h
Contraindications	Documented hypersensitivity
Interactions	Drugs with anticholinergic properties, such as dronabinol, may increase toxicity; albuterol increases effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Not indicated for single-agent treatment of acute bronchospasm given its relatively slow onset (20 min); caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

Drug Name	Ipratropium and albuterol (Combivent) -- Anticholinergic agent with anti-secretory properties. When applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Ipratropium has been found effective in severe asthma exacerbations only. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized. Albuterol is a beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility. Recommended to "test spray" 3 times before using first time and in cases where aerosol has not been used for >24 h.
Adult Dose	Nebulizer: 3 mL q20min for 3 doses, then prn MDI: 4-8 puffs q20min prn up to 3 h
Pediatric Dose	Nebulizer: 1.5 mL q20min for 3 doses, then prn MDI: 4-8 puffs q20min prn up to 3 h
Contraindications	Documented hypersensitivity
Interactions	Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol increases effects of ipratropium Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

Drug Name	Theophylline (Theo-Dur, Theo-24, Aminophylline) -- Purported efficacy thought to be due to potentiation of exogenous catecholamines, stimulation of endogenous catecholamine release, and diaphragmatic muscular stimulation. Effects as bronchodilator are mild, and toxicity (levels >20 mg/dL) is common.
Adult Dose	Loading dose: 6 mg/kg lean body weight IV over 20-30 min Drip (1 g in 250 mL D5W): 0.5-0.7 mg/kg/h IV
Pediatric Dose	1 mg/kg/h IV
Contraindications	Documented hypersensitivity; uncontrolled arrhythmias; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders
Interactions	Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism; do not inject IV solution faster than 25 mg/min; patients with pulmonary edema or liver dysfunction at greater risk of toxicity because of reduced drug clearance

Drug Name	Ketamine (Ketalar) -- Acts on cortex and limbic system, decreasing bronchospasm. A dissociative anesthetic agent.
Adult Dose	Initial dose: 1-4.5 mg/kg IV Maintenance dose: One third to one half initial dose IV
Pediatric Dose	Initial dose: 0.5-2 mg/kg IV Maintenance dose: One third to one half initial dose
Contraindications	Documented hypersensitivity; thyrotoxicosis
Interactions	Increases CNS effects of narcotics, barbiturates, and hydroxyzine; thyroid hormones and muscle relaxants increase toxicity
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in patients with intracranial hypertension; may increase bronchial secretions, prompting some practitioners to administer concomitant antisecretory agent (ie, glycopyrrolate) routinely as preventive measure Resuscitative equipment should be immediately available when administering this medication

Drug Category: Inhaled volatile anesthetics -- These agents may aid in smooth muscle relaxation.

Drug Name	Halothane (1-2%) -- Leads to moderate effects on bronchial muscular relaxation and causes bronchodilation.
Adult Dose	24 years: 0.84 MAC 42 years: 0.76 MAC 81 years: 0.64 MAC
Pediatric Dose	Infants: 1.08 MAC 3 years: 0.91 MAC 10 years: 0.87 MAC 15 years: 0.92 MAC
Contraindications	Documented hypersensitivity
Interactions	Caution when administering epinephrine or norepinephrine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hepatic dysfunction may occur

FOLLOW-UP

Section 8 of 11

Further Outpatient Care:

• In general, the patient may be discharged from the hospital if the PEF or the patient's personal best expiratory flow rate is 70% or more of predicted rate and if symptoms are minimal or absent.

• Patients who have mild symptoms but have PEF of 50-69% of predicted or personal best could be considered for discharge if high-risk factors for relapse are not present. However, patients with PEF of 50-69% of predicted or personal best who may be unable to obtain medications for socioeconomic reasons have a lower admission threshold.

• Consider referral to an asthma specialist, as consultation and guidance have been shown to reduce the risk of future ED visits.

• ED staff should emphasize the importance of follow-up care after the ED visit for education about asthma and for initiation of environmental and pharmacologic interventions that can prevent future exacerbations and otherwise improve the patient’s quality of life.

• Asthma education efforts after the ED visit usually can address a much larger number of issues than during the actual ED visit, when teaching needs to be extremely focused. Nevertheless, a preventive message should be delivered at all clinical encounters.

• At the more comprehensive post-ED visit session—in the allergist or pulmonologist office, or in special asthma programs set up by the ED—potential topics include asthma triggers (viral URIs, allergens such as cats), the proper use of inhaler medications, the use of spacers and value of oral rinsing after use of inhaled corticosteroids, and the significance of nocturnal exacerbations (10-fold more asthmatics are intubated at night). The patient should have a written action plan telling him or her what to do in response to certain symptoms or certain PEF values. Many educational sessions are based on the action plan and its use.

• ED staff also should emphasize the importance of not running out of medications or even running low on medications (note MDI only reliable for number of actuations listed on the canister; almost no patient counts the number of actuations, and floating techniques for canister are unreliable and no longer recommended). Tell the patient to keep an extra canister, especially of inhaled beta-agonists.

• In general, discharging a patient on effective inhaled corticosteroids (eg, medium-dose budesonide or fluticasone) is beneficial. Most ED patients will not follow up with a primary care physician (PCP) in the weeks after the ED visit and will not receive inhaled corticosteroids unless it is started at ED or hospital discharge.

Complications:

• Complications of severe asthma include the following:

• Respiratory distress/arrest

• Death

Prognosis:

• The prognosis is excellent if compliant with proper therapies.

• Risk factors for death from asthma include labile asthma, history of more than 3 ED visits or more than 2 hospitalizations, either ICU admission or endotracheal intubation within the past year, recent withdrawal from corticosteroids, current use of systemic corticosteroids, comorbid conditions (eg, heart disease, psychiatric disease, drug abuse), and concomitant adverse socioeconomic conditions.

Patient Education:

• For excellent patient education resources, see eMedicine's Asthma Center. Also, visit eMedicine's patient education articles Asthma, Asthma FAQs, Asthma in Children, and Understanding Asthma Medications.

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• Presumptive diagnosis of asthma, especially new onset. Asthma may actually be a misdiagnosis and may reflect CHF, myocarditis, multiple pulmonary emboli, surreptitious vocal cord dysfunction, or panic disorder/hyperventilation.

TEST QUESTIONS

Section 10 of 11

CME Question 1: Paramedics bring a 21-year-old woman with acute asthma to the ED after she wheezed most of the night. She has been treated with inhaled beta-agonists en route. She has an intravenous access site, is receiving supplemental oxygen, and is on an ECG monitor. On arrival she is profusely diaphoretic, highly agitated, uncooperative, and pulls off her oxygen mask repeatedly. She is wheezing faintly and moving air poorly. She cannot speak. Which of the following would be the most important immediate maneuver?

A: Arterial blood gas (ABG) measurement
B: Discussion with her primary care provider for further history
C: Preparation for rapid sequence intubation
D: Systemic corticosteroids
E: Inhaled ipratropium

The correct answer is C: This patient is presenting with severe hypoxia and probable hypercarbia. Central cyanosis also would be present. The patient is close to being too agitated to perform further treatments by a nebulizer. She needs oxygen immediately to avert a respiratory arrest. An ABG would take precious time to perform and would provide only baseline objective data that corroborates the patient’s clinical presentation. Speaking to her private physician at this point in her presentation would be irrelevant. Systemic corticosteroids and ipratropium are important but can wait until the patient is oxygenated adequately.

CME Question 2: A 21-year-old, nonsmoking, obese woman who is 10 weeks postpartum presents with a history of asthma recently diagnosed by her primary care provider. She has no history of allergies or atopic dermatitis. She denies having an upper respiratory infection (URI). She has had 3-4 ED visits over the last month since her diagnosis of asthma. She is on inhaled beta-agonists, inhaled corticosteroids, and prednisone 60 mg/d. Her asthma has been under only fair control despite this regimen. She awakens several times each night to use her inhaler. She presents today with wheezing for the previous 12 hours, BP 160/80, pulse 120, respirations 32, and temperature 98.8°F. Pulse oximetry on room air reveals an oxygen saturation of 72%. PEF is 36% of predicted. She has staccato speech. Mild central cyanosis is observed. She is using accessory muscles, is not diaphoretic, and is sitting up in a tripod position.

Examination reveals an increased S1 heart sound; inspiratory wheezing greater than expiratory wheezing; and 2+ pitting peripheral edema. In addition to beta-agonists and admission, what is the appropriate treatment for this patient?

A: Prompt endotracheal intubation
B: Measurement of serum potassium to exclude life-threatening hypokalemia
C: Intravenous ketamine
D: Consider anticoagulation
E: Arterial blood gas (ABG) measurement

The correct answer is D: That the presumed asthma was new onset and the patient was not atopic, had no URI, and had not responded well to the usual asthma medications (including 60 mg of prednisone) leads to consideration of diagnoses other than asthma. Hypoxemia out of proportion to the severity of asthma, along with risk factors for thromboembolic disease (eg, obesity, postpartum), suggest the presence of multiple pulmonary emboli. The peripheral edema also suggests deep vein thrombosis. Multiple pulmonary emboli may present with wheezing in up to 10% of cases and may simulate acute asthma. Without anticoagulation, this disease has a mortality rate of 50%. This patient does need prompt supplemental oxygenation. ABGs are indicated if the PEF is less than 25% of predicted.

Pearl Question 1 (T/F): A gender difference exists in hospitalization rates of adults with acute asthma.

The correct answer is True: The female-to-male ratio for adult admissions is 2:1.

Pearl Question 2 (T/F): The most common acid-base abnormality in patients with acute asthma is acute respiratory alkalosis.

The correct answer is True: Acute respiratory alkalosis is the most common acid-base abnormality in acute asthma. This is due to hypocapnia secondary to hyperventilation.

Pearl Question 3 (T/F): The absence of wheezing signifies that asthma is not present.

The correct answer is False: The absence of wheezing and a silent chest may signify that the asthma is so severe that air movement is inadequate to generate the sound of a wheeze.

Pearl Question 4 (T/F): If 2-3 inhalations of beta-agonists have not decreased bronchospasm, prednisone has been demonstrated to reliably improve airflow within the 3 hours of a typical ED stay.

The correct answer is False: Prednisone probably will not affect bronchospasm for up to 6 hours, with initial effects seen after 3-4 hours in some patients. Adjunct therapies for severe exacerbations that appear refractory to inhaled beta-agonists include inhaled ipratropium, intravenous magnesium sulfate. Although data are sparse, the fastest relief might come from intramuscular epinephrine, administered as 0.3-0.5 mL (0.3-0.5 mg) of 1:1000 solution.

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Section 11 of 11

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