Magnitude of the Problem

Each year in the United States, acute asthma accounts for approximately 1.8 million emergency department visits, 497,000 hospitalizations, and 3800 deaths.¹ All too commonly, failure to achieve adequate outpatient control lies at the crux of the problem. Asthma control is achieved in a minority of patients, largely due to the underuse of antiinflammatory agents, and poor control is a risk factor for asthma exacerbation.² More than half of current asthmatics had one or more attacks during the preceding year, and there appears to be a subset of patients who are prone to exacerbations. Factors underlying the exacerbation-prone phenotype include cigarette smoking, medication nonadherence, psychosocial factors, poverty, obesity, and alterations in host cytokine response to viral infections.³ The rate of asthma death is higher in blacks than whites and in patients aged 65 and older. Patients who require mechanical ventilation for asthma have a mortality rate of less than 10% and are most likely to die of tension pneumothorax or nosocomial infection.⁴ Fortunately, the rate of asthma death (which had increased from 1980 to 1995) has decreased each year since 2000. Risk factors for fatal or near-fatal asthma are listed in Table 60-1.

TABLE60-1 Risk Factors for Fatal or Near-Fatal Asthma

Pathophysiology of Acute Airflow Obstruction

Less than 15% of asthmatics have rapid-onset exacerbations. These are predominantly bronchospastic events resulting in significant airflow obstruction within minutes to a few hours. They occur from exposure to an allergen or irritant, stress, inhalation of illicit drugs, or the use of a nonsteroidal antiinflammatory agent or beta-blocker in susceptible patients. The trigger is generally not infectious and may remain unidentified.

Asthma attacks most commonly evolve over 24 hours and are associated with increasing airway wall inflammation and mucus plugs. These exacerbations are commonly triggered by viral infections (e.g., rhinovirus, influenza virus, respiratory syncytial virus) or mycoplasma and take longer to resolve.

Regardless of the tempo of the attack, acutely ill asthmatics develop critical airflow obstruction. The time available for expiration (less than 2 seconds in a patient breathing 30/min) is insufficient for full exhalation, resulting in gas trapping and dynamic lung hyperinflation (DHI). Trapped gas elevates alveolar volume and pressure relative to mouth pressure at end-expiration, a state referred to as auto-PEEP.⁵ Auto-PEEP must be overcome by forcefully lowering pleural pressure during spontaneous inspiration, which increases the inspiratory work of breathing. At the same time, dynamic hyperinflation increases elastic work of breathing. Dynamic hyperinflation also decreases diaphragm force generation by placing the diaphragm in a mechanically disadvantageous position. Dynamic hyperinflation may be self-limiting because increases in lung volume increase lung elastic recoil pressure and airway diameter to augment expiratory flow. In the end, an imbalance between increased respiratory system load (both resistive and elastic) and decreased respiratory muscle strength may result in respiratory failure.⁶

Hypoxemia results from decreased ventilation () to perfused () alveolar-capillary units. The severity of hypoxemia roughly tracks the severity of obstruction, but in recovering patients, airflow rates may improve faster than PaO₂ and inequality, indicating that larger airways recover faster than smaller airways. Multiple inert gas elimination technique (MIGET) analysis also demonstrates small areas of high relative to and slightly increased physiologic dead space in acute asthma. This may result from decreased blood flow to hyperinflated lung units. Elevated dead space and decreased minute ventilation in the critically hyperinflated and fatiguing patient underlie the development of hypercapnia in severe exacerbations.

Large swings in intrathoracic pressure accentuate the normal inspiratory fall in systolic blood pressure, a phenomenon referred to as pulsus paradoxus. During vigorous inspiration, intrathoracic pressure falls, lowering right atrial and right ventricular pressures and thereby augmenting right ventricular (RV) filling. Enhanced right-sided filling shifts the intraventricular septum leftward, causing a conformational change in the left ventricle (LV), LV noncompliance, and incomplete LV filling. Furthermore, LV filling may be impeded by dynamic hyperinflation, causing tamponade-like physiology; LV emptying is impaired by large negative pleural pressures and increased LV afterload.

During forced expiration, high intrathoracic pressures impede right-sided filling during asthma exacerbations. The net result of cyclical changes in pleural pressure is pulsus paradoxus. Importantly, however, an increase in pulsus paradoxus does not occur when decreased respiratory muscle strength limits the magnitude of pleural pressure change.

Clinical Features

Dyspnea, cough, wheeze, and increased work of breathing are the hallmarks of acute asthma. Patients with moderate to moderately severe attacks are tachypneic and in mild to moderate respiratory distress. They have expiratory phase prolongation, difficulty speaking in long sentences, and audible wheezes. Arterial blood gases commonly reveal hypoxemia and acute respiratory alkalosis. A more severe attack leads to upright positioning, diaphoresis, monosyllabic speech, respiratory rate above 30/min, accessory muscle use, pulse above 120/min, pulsus paradoxus greater than 25 mm Hg, hypoxemia, and normo- or hypercapnia. Depressed mental status, paradoxical respiration, bradycardia, absence of pulsus paradoxus from respiratory muscle fatigue, and a quiet chest signal an impending arrest. The emergence of wheezes in these patients is generally a good marker that airflow has improved. Thus posture, speech, and mental status allow for a quick appraisal of severity, response to therapy, and need for intubation.⁷

The common cardiac response to acute asthma is sinus tachycardia. Supraventricular and ventricular arrhythmias occur rarely. Severe exacerbations may also cause right heart strain and myocardial ischemia.

Differential Diagnosis

“All that wheezes is not asthma” is an adage worth remembering. In heavy smokers over the age of 40, consider an acute exacerbation of chronic obstructive pulmonary disease. In patients with congestive heart failure, bear in mind that elevated left atrial pressure can cause wheezing. Pulmonary embolism rarely causes wheeze, but this possibility should be considered when dyspnea is out of proportion to signs and measures of expiratory flow. Vocal cord dysfunction (and other causes of upper airway obstruction) should be considered when there is stridor, normal oxygenation, or resolution of airflow obstruction after intubation. Tracheal stenosis (e.g., subglottic stenosis from prior intubation or bronchogenic cancer) may also present with breathlessness and wheezing. Finally, foreign-body aspiration should be considered in the very young and old, in individuals with altered mental status or neuromuscular disease, and if symptoms developed after eating or dental work. Pneumonia should be considered in the febrile patient with cough and phlegm when there are localizing signs on physical examination, and hypoxemia does not correct with low-flow oxygen.

Peak Flow Measurements

To avoid underestimating the severity of an asthma exacerbation, it is important to objectively measure the degree of airflow obstruction. Clinicians often underestimate the degree of obstruction and may alter therapy after peak expiratory flow rate (PEFR) determination. Patients perform slightly better than clinicians at estimating severity, but there is still variability in perception. Peak flow measurements should be deferred in patients with severe exacerbations; the maneuver can worsen bronchospasm even to the point of arrest.

The change in PEFR or FEV₁ (forced expiratory volume in the first second of expiration) predicts the need for hospitalization. Several studies have demonstrated that failure of initial therapy to improve expiratory flow significantly after 30 to 60 minutes predicts a refractory course requiring continued treatment in the emergency department (ED) or hospitalization.

Acid-Base Status

Arterial blood gas determination is recommended in patients with severe attacks (e.g., when FEV₁ is less than 1 L or PEFR is less than 200 L/min). However, serial blood gases are generally not necessary unless the patient is mechanically ventilated. Hypoxemia and respiratory alkalosis are common in mild to moderate exacerbations. Eucapnia and hypercapnia indicate a severe exacerbation, but they are in and of themselves not sufficient reasons for intubation, because these patients may still respond adequately to pharmacotherapy. Conversely, the absence of hypercapnia does not preclude a life-threatening attack.

In response to acute respiratory alkalosis of sufficient duration, there may be renal wasting of bicarbonate and development of a post-hypocapnic metabolic acidosis. Lactic acidosis occurs, particularly in patients with labored breathing who receive parenteral β-agonists.

Chest Radiography

In classic cases of acute asthma, the chest x-ray rarely affects management. A chest x-ray should be obtained when there are localizing signs on examination, concerns regarding barotrauma, or questions regarding diagnosis. Chest x-rays are also indicated in intubated patients to confirm proper endotracheal tube position.

Emergency Department Disposition

Asthmatic patients with inadequate response to albuterol in the ED invariably require hospital admission or prolonged treatment in an ED holding area (see later).⁸ Approximately one-third of patients are nonresponders to albuterol (Figure 60-1), which is not necessarily explained by prior heavy use of this medication. Rather, nonresponsiveness suggests a significant component of airway wall inflammation and the presence of intraluminal mucus. Albuterol nonresponders have negligible (i.e., <10%) changes in their PEFR after 30 to 60 minutes of therapy. These patients should be admitted to the hospital, as should patients with other markers of a severe attack such as a PEFR less than 40% of predicted or personal best PEFR, or deterioration despite ED treatment. Patients with respiratory failure, need for frequent albuterol treatments, fatigue, altered mental status, and cardiac arrhythmias require intensive care unit admission. Patients with an incomplete response to treatment in the ED, defined by improved but persistent symptoms and a PEFR or FEV₁ between 40% and 69% of predicted, should be considered for admission, although selected patients safely return home with appropriate treatment and follow-up. Patients with a good response to treatment may be discharged home with appropriate instructions for anti-inflammatory therapy. These patients have a PEFR ≥ 70% an hour after their last treatment, a clear chest, and are in no distress.

Figure 60-1 Dose-response relationship to albuterol 4 puffs (400 µg) every 10 minutes in 116 acute asthmatics. Sixty-seven percent of patients obtained discharge criteria after administration of 2.4 mg albuterol within 1 hour; half of responders met discharge criteria after 12 puffs. Patients with a blunted cumulative dose-response relationship were hospitalized.

(Reproduced with permission from Rodrigo C, Rodrigo G. Therapeutic response patterns to high and cumulative doses of salbutamol in acute severe asthma. Chest. 1998;113:593.)

Oxygen

Supplemental oxygen should be provided to maintain arterial oxygen saturations greater than 90% (>95% in pregnancy). This improves oxygen delivery to tissue beds including the respiratory muscles and reverses hypoxic pulmonary vasoconstriction. Oxygen further protects against β-agonist-induced pulmonary vasodilation and increased blood flow to low units. Oxygen saturation should be monitored until there is clear clinical progress, remembering that improved oxygenation may lag behind improved airflow rates.

Pharmacologic Management

Selected drugs used in the treatment of acute asthma are presented in Table 60-2. Brief discussions of a few of the more common therapeutic agents employed to treat severe asthma exacerbation follow.

TABLE60-2 Selected Drugs Used in the Treatment of Acute Asthma