Asthma

Asthma is a chronic disease characterized by increased airway responsiveness to various stimuli. This causes widespread narrowing of the lower airways that reverses either spontaneously or with treatment. Although the exact path physiology of asthma is complex and poorly understood, inflammation is thought to play a central role. Pathologic changes that occur in asthma include smooth muscle hypertrophy, mucosal edema, and mucous plugging. Asthma affects 4-5% of adults and 10% of children. Onset usually occurs in children and young adults.

Etiology and Risk Factors

• Asthma is commonly classified as allergic (extrinsic) or no allergic (intrinsic).
• Allergic asthma is more common and is responsible for the majority of childhood asthma and a significant portion of adult disease. These patients are sensitive to specific inhaled allergens. Patients with allergic asthma frequently have a personal and family history of allergic diseases, including allergic rhinitis and atopic dermatitis. In contrast to patients with intrinsic asthma, those with allergic asthma have increased levels of immunoglobulin E (IgE). Inhalation of an allergen induces a response in two phases.
• The early response usually begins within minutes of exposure and lasts up to period of several hours. Caused by mast cell degranulation. Mediator release subsequently induces bronchoconstriction and an inflammatory reaction.
• The late response is characterized by airway inflammation that results in further bronchoconstriction and mucous production. Symptoms may persist for days to weeks after the initial exposure.
• No allergic asthma is associated with numerous stimuli including exercise, emotion, air pollution, cigarette smoke, medications, and occupational exposures.

• A definitive diagnosis is made via pulmonary function tests (PFTs) that demonstrate reversible airway obstruction. PFTs are not practical for use in the emergency department (ED) where the diagnosis is made clinically.
• In stable patients, historical information can be obtained that may help guide therapy and disposition. There are several factors associated with poor outcome.
• History of prior intubations for ARF secondary to asthma
• Multiple or recent hospitalization(s) for asthma exacerbation
• Recent use of corticosteroids
• Other important information includes the time of onset, inciting factors, and use of medications prior to arrival.
• Patients generally complain of dyspnea and cough. Severity ranges from mild to life threatening. Note that dyspnea is likely unrelated to hypoxia and may not resolve with supplemental oxygen. The cough can be either dry or productive. Patients with "cough-variant asthma" present with a nonproductive cough that tends to be nocturnal. They may not have audible wheezing. These patients have ventilatory impairments demonstrable with PFTs and usually experience relief with bronchodilator therapy.
• General appearance, vital signs, and pulmonary evaluation should be assessed as previously discussed (see ARF). Patients often have tachypnea and tachycardia that should improve with appropriate asthma treatment. A pulses paradox is associated with acute asthma but is not a practical aspect of the ED evaluation. Common auscultatory findings include wheezing, decreased breath sounds, and prolongation of the expiratory phase. Absence of wheezing may be indicative of severe airway obstruction. Reexamination after bronchodilator therapy in such patients is often notable for increased wheezing. AMS, increased work of breathing, hypoxia, and hypercarbia indicate ARF and mandate immediate intervention.
• While asthma is mainly a clinical diagnosis, hemoptysis, various diagnostic modalities can contribute to management and disposition.
• Pox-Saturation should be continuously monitored on all asthma patients (see Part A, Diagnosis, for discussion of Pox). Any patient with a saturation less than 90% should be considered severely hypoxic and treated accordingly.
• ABG-Blood gas assessment is not routinely indicated but can help guide ventilator management and determine the degree of hypercarbia/hypoxia in patients with severe exacerbation. During an acute exacerbation, the ABG usually shows a respiratory alkalosis. Normal or increasing pCO2 reflects deterioration in ventilation although this should also be clinically evident.
• Pulmonary function testing/Peak flow—As previously discussed, PFTs are not a routine aspect of the ED evaluation. Peak expiratory flow rate (PEFR) provides a means of assessing pulmonary function at the bedside although patient cooperation is required. PEFR values do not correlate well with prognosis, and there is no absolute value that mandates admission. It is best used serially to monitor the effects of therapy on patients with mild to moderate disease. Ideally, PEFR in the ED is compared against the patients known baseline. Measurements can also be compared to predicted levels using nomograms that consider age, sex, and height. In general for adults patients, PEFR less than 300 indicates a mild exacerbation, PEFR less than 200 a moderate exacerbation, and PEFR less than 100 a severe exacerbation.
• CXR—In mild to moderate asthma exacerbations, routine CXR is not necessary. It is helpful for identification of complications such as pneumothorax. CXR is also indicated if the patient does not improve with therapy or has fever, focal findings on pulmonary exam, pleuritic chest pain, or hypoxia. Patients presenting with a first episode of wheezing and those with an unclear diagnosis should have CXR to evaluate for underlying pathology.
• Laboratories rarely influence management and are not routinely indicated. The decision to obtain laboratory screening should be based upon the patient’s age, medication use, and other comorbid conditions. An increased leukocyte count (WBC) is consistent with both infection and steroid use. However, a normal WBC does not exclude infection. Also consider a theophylline level in patients taking that medication.
• Differential Diagnosis
• The emergency physician (EP) must always search for a cause of acute exacerbation especially in those patients with severe symptoms. Allergen exposure is the most likely but respiratory infection, PTX, and pulmonary embolism (PE) are important and potentially fatal problems that must be identified.
• The EP should remember that "all that wheezes is not asthma." Other conditions to consider include COPD, congestive heart failure, allergic reaction, airway obstruction, and pulmonary embolism. A directed history and physical examination, along with proper use of diagnostic testing, will help to differentiate these entities.

Treatment

Respiratory Support

• Oxygen can be given liberally since asthmatic patients do not chronically retain CO2. The amount and route primarily depend upon the patient’s symptoms and degree of hypoxia.
• NPPV has been shown to be effective in improving gas exchange and avoiding intubation in some asthmatic patients (see "Acute Respiratory Failure"). NPPV is not appropriate for patients with AMS and an obviously ineffective respiratory effort.
• Endotracheal Intubation
• The decision to intubate is purely clinical. There are no ABG parameters or CXR findings that mandate this intervention. Patients with severe refractory hypoxia, altered mental status, severely increased work of breathing, and/or ineffective respirations are candidates for immediate intubation.
• In the conscious patient, rapid sequence induction (RSI) is the safest method for endotracheal tube placement. Agents commonly used for RSI include a benzodiazepine in conjunction with a paralytic agent. Ketamine, in addition to its analgesic and anesthetic properties, is a bronchodilator and therefore should be considered the induction agent of choice in young asthmatics. In older patients with coronary artery disease, the cardiovascular risks of ketamine may outweigh the benefits. There are no specific contraindications to paralytic agents during RSI of the acute asthmatic patient.
• Preoxygenation should be attempted prior to intubation. However, this is sometimes not possible for patients in extremis. Furthermore, oxygen saturation may decline very rapidly during intubation.
• Oral intubation is preferred to nasotracheal intubation because a larger tube can be inserted. This allows for adequate suction and for bronchoscopy if needed.
• Ventilator Management
• The intubated asthmatic patient is at risk for barotraumatic complications such as PTX, pneumomediastinum, or subcutaneous emphysema. The goal of mechanical ventilation is to supply the lowest minute ventilation that yields adequate gas exchange keeping peak airway pressures (PAP) below 35 cm H2O. Suggested initial adult ventilator settings include FiO2 of 100%, tidal volume of 6-8 ml/kg, ventilatory rate of 10, and inspiratory time/expiratory time (I/E) ratio of 1:3 or 1:4. FiO2 can be titrated based on Pox and/or ABG.
• Permissive hypercapnia is a strategy sometimes used to help control PAP. Patients are intentionally hypoventilated and airway pressures minimized via low tidal volume and RR. PaCO2 is permitted to rise and pH to fall, generally to a level of around 7.25. In severe cases, pH can be further decreased and a sodium bicarbonate infusion initiated. Oxygenation is maintained via high FiO2.
• After intubation, continued sedation and paralysis allow for maximal relief of the respiratory muscles and for permissive hypercapnia. This can be achieved with longer acting benzodiazepines and paralytic agents. Subsequent dosing of ketamine is also appropriate.
• Patients may also develop hypotension secondary to increased intrathoracic pressure and impaired venous blood return to the right ventricle resulting in decreased cardiac output. This must be differentiated from tension PTX. Both will also cause an elevation of PAP. If the former is suspected, the patient should be disconnected from the ventilator and manually ventilated at a slower rate (6 to 8 breaths per minute). This will allow for exhalation of trapped air. In addition, a CXR should be ordered and the patient suctioned. If a tension PTX is suspected, immediate decompression of the affected side by needle thoracostomy is indicated.

Medications

• Beta2 Agonists
• Inhaled ß2 agonists are the mainstay of therapy for acute asthma exacerbation. These agents relax bronchial smooth muscles and reverse bronchospasm. Albuterol is the most commonly used agent and is generally delivered by nebulizer. Onset of action is less than 5 min, and repetitive administration produces incremental effect. Nebulized albuterol is usually given in 2.5-5 mg increments every 15-20 min as needed. It can be given continuously for patients with severe symptoms. There is no defined maximum dose. Administration is usually limited only by symptoms (tremor, tachycardia, nausea).
• Studies have shown that metered dose inhalers (MDIs) are as effective as nebulizers.
  However proper MDI use is essential and a severe exacerbation may preclude proper use.
• Remember that intubation does not cure asthma. Intubated patients should continue to receive aggressive in-line ß2 agonists.
• Levalbuterol is the single (R) isomer preparation of albuterol, as opposed to traditional racemic albuterol, which is a 50/50 mixture of the (R) and (S) isomers, the (S) component being inactive. It is thought to have similar efficacy to racemic albuterol but fewer nonrespiratory side effects. The cost of levalbuterol is about five times that of racemic albuterol. The benefit of this new preparation over standard albuterol is debatable.
• Although multiple studies have demonstrated the advantages of inhaled ß2 agonists over systemic medications, it has been suggested that inhaled medications may be unable to reach critical areas in patients with severe asthma and profoundly impaired airflow. In these severe circumstances, terbutaline or epinephrine may be administered subcutaneously. The adult dosing for epinephrine is 0.3-0.5 mg of 1:1000 solution every 15-20 min as needed, up to 3 doses. Terbutaline dosage is 0.25-0.5 mg every 15-20 min as needed. Epinephrine should be used with caution in elderly patients and those with cardiovascular disease.
• Inhaled Anticholinergics
• These agents block muscarinic receptors preventing smooth muscle contraction and diminishing mucous gland secretions.
• Ipratropium bromide is the most commonly used agent. It is not to be used as single agent therapy but has been shown to be effective for the severe asthma treatment when added to albuterol. Inhaled ipratropium does not appear to result in significant systemic side effects unlike other anticholinergic agents such as atropine.
• Ipratropium is delivered by nebulization and can be mixed with albuterol. The dose is 0.25-0.50 mg every 15-20 min, up to three doses.
• Most of the studies that support the beneficial effect of ipratropium used with small to moderate doses of albuterol. Thus, it is possible that the same benefit may be obtained by simply using higher doses of albuterol without ipratropium.
• Corticosteroids
• Corticosteroids suppress inflammation and have been shown to improve patient outcomes, prevent relapses, and prevent hospital admission. There is little immediate benefit because of the delayed onset of these agents (about 6 h). Corticosteroids are probably unnecessary in mild asthma, but should be given in moderate to severe cases and in any patient who does not respond promptly to inhaled ß2 agonists.
• Oral prednisone and intravenous (IV) methylprednisolone are the most commonly used agents. There is no difference between these two medications in terms of efficacy or onset of action. Prednisone is less expensive and more easily administered and should be given to the majority of patients. Methylprednisolone is preferred in patients who are unable to take oral medications due to vomiting or respiratory distress. The adult dose of prednisone is 60 mg and methylprednisolone 125 mg.
• Patients discharged from the ED after being treated with corticosteroids should be continued on outpatient therapy for 5-7 days. This dosing regimen does not require tapering.
• Inhaled corticosteroids have few systemic side effects and are beneficial in long-term management but currently have little use in the ED.
• Methylxanthines
• The methylxanthines have multiple effects including bronchodilation and enhancement of diaphragmatic contraction. The mechanisms of action are not well defined. Use of methylxanthines in the ED is discouraged due to side effect profiles, complicated dosing, and lack of established efficacy.
• If the decision is made to use intravenous aminophylline for a patient with refractory disease, frequent serum levels are necessary in order to avoid toxicity. Note that elimination rates are highly variable. For patients already taking theophylline, a baseline level is mandatory before beginning acute therapy.
• Magnesium sulfate (Mg) is a weak bronchodilator and a second-line agent for asthma exacerbations. The most recent data suggests that Mg benefits only the most severe asthmatic patients and should not be given routinely. Mg is inexpensive and safe in patients with normal renal function. The adult dose is 2 g IV over 10-15 min.
• Heli-ox is a combination of helium and oxygen that is usually administered in a 70%/ 30% mixture. Heli-ox is thought to improve laminar gas flow through airways, resulting in improved gas exchange and decreased work of breathing. Although early case reports were positive, subsequent clinical studies have shown little benefit and use of heli-ox remains controversial. Heli-ox is safe and inexpensive, and many physicians use this as adjunctive therapy in severe cases or in intubated patients with elevated PAP.

Disposition

• Disposition is dependent upon the patients response to therapy. In general, patients with complete or near-complete resolution of symptoms and a PFR of at least 300 (or near the patient’s baseline) can be discharged. Patients who don’t meet discharge criteria who have mild to moderate symptoms can be admitted to a ward bed. Patients with more severe symptoms should be admitted to a monitored bed where timely respiratory assessment and therapy is available. Intubated patients and those with the potential for respiratory failure require ICU admission.
• All patients discharged from the ED should receive bronchodilator therapy ± corticosteroids.