Severe asthma exacerbation in adults

Magnitude of the problem and risk factors

Each year in the United States, acute asthma accounts for approximately 1.8 million emergency department (ED) visits, 190,000 hospitalizations, and 3500 deaths. Although death rates have decreased slightly over the last 20 years, African Americans, women, and older patients continue to be at increased risk. For the subgroup of patients requiring hospital admission, in-hospital mortality is very low in patients not requiring ventilatory support. Mortality in intubated and mechanically ventilated patients is often associated with out-of-hospital cardiopulmonary arrest. ^,

Inadequate outpatient asthma control increases the risk of poor outcomes, including death. Risk factors for an exacerbation-prone phenotype include cigarette smoking, medication nonadherence, psychosocial factors, poverty, obesity, severe sinus disease, frequent infections, and alterations in host cytokine response to viral infections. However, even patients with mild asthma are at risk for serious exacerbations. Risk factors for fatal or near-fatal asthma are listed in Table 63.1 .

Pathophysiology of acute airflow obstruction

Rapid-onset exacerbations are a rare but distinct form of acute asthma. These exacerbations are predominantly bronchospastic events that evolve over minutes to hours and follow exposure to allergens or irritants, stress, illicit drugs, or the use of nonsteroidal antiinflammatory agents or beta-blockers in susceptible patients. They are generally not triggered by infection. More commonly, asthma attacks evolve over 24 hours or longer and are associated with increased airway wall inflammation, bronchospasm, and mucous plugs. These exacerbations take longer to resolve and may be triggered by viral infections or Mycoplasma pneumoniae.

Regardless of trigger or tempo, the common endpoints of a severe exacerbation include critical expiratory airflow obstruction, inadequate expiratory time, dynamic hyperinflation (DHI), increased work of breathing, and decreased diaphragm force generation. A patient with a respiratory rate (RR) in the high twenties or thirties has less than 2 seconds to exhale the tidal breath. If this time is insufficient to fully exhale, lung volumes increase and tidal breathing occurs at higher lung volumes, where respiratory system compliance is low and the respiratory muscles that drive inflation are less efficient. DHI is self-limiting if hyperinflation increases lung elastic recoil pressure and airway diameter to enhance expiratory flow. At the end of exhalation, incomplete gas emptying elevates alveolar volume and pressure, a state referred to as auto–positive end-expiratory pressure (auto-PEEP). Overcoming the effects of auto-PEEP requires increased inspiratory work to drop pleural pressures enough to generate inspiratory flow. Concurrent with increases in resistive and elastic loads is decreased diaphragm force generation from the mechanical effects of DHI, fatigue, and acidemia, increasing the risk of respiratory arrest and death.

Hypoxemia results from a decrease in ventilation ( $\stackrel{·}{V_A}$ ) relative to perfusion ( $\stackrel{·}{Q}$ ) in alveolar-capillary units. Hypoxemia severity generally tracks the severity of airflow obstruction, but in recovering patients, spirometry and peak flow may improve faster than partial pressure of oxygen (Pao ₂ ) and $\stackrel{·}{V_A}/\stackrel{·}{Q}$ inequality, indicating that larger airways recover faster than smaller airways. Acutely ill asthmatics may also have small areas of high $\stackrel{·}{V_A}$ relative to $\stackrel{·}{Q}$ and increased physiologic dead space when blood flow decreases to hyperinflated units. Although elevated physiologic dead space can contribute to hypercapnia, alveolar hypoventilation is the more likely cause in acute asthma.

Large swings in intrathoracic pressure accentuate the normal inspiratory fall in systolic blood pressure, a phenomenon called pulsus paradoxus (PP). During forceful inspiration, intrathoracic pressure falls, lowering right atrial and right ventricular (RV) pressures and augmenting RV filling. Enhanced right-sided filling shifts the intraventricular septum leftward. This results in decreased left ventricular (LV) compliance and incomplete LV filling. DHI further impedes LV filling by causing tamponade-like physiology, and it increases LV afterload.

Forced exhalation increases intrathoracic pressures and impedes right-sided filling. The net result of these cyclical changes in pleural pressure is increased PP. A decline in PP generally signals improvement, with the important exception that fatigue and inability to generate large pleural pressure swings also drop PP.

Clinical features

The hallmarks of a moderate to moderately severe exacerbation are tachypnea and respiratory distress. Patients may have difficulty speaking in long sentences and present with wheezing and prolongation of the expiratory phase. Hypoxemia and respiratory alkalosis occur commonly. Severe exacerbations are signaled by upright positioning, diaphoresis, monosyllabic speech, RR over 30/min, accessory muscle use, tachycardia, and a PP greater than 25 mm Hg. ^, Hypoxemia with normocapnia or hypercapnia indicates a severe exacerbation. Decreased mental status, paradoxical breathing, bradycardia, absence of PP from fatigue, and a quiet chest signal impending arrest. Severe exacerbations may also be complicated by tachyarrhythmias, RV strain, and myocardial ischemia. Posture, speech, and mental status allow for quick appraisal of severity, response to therapy, and need for intubation. The emergence of wheezes in patients presenting initially with a quiet chest from poor air movement suggests improved airflow rates and clinical status. Additionally, it is worth considering that “all that wheezes is not asthma.” Table 63.2 lists other diagnostic considerations.

Peak flow measurements

Early measurement of the peak expiratory flow rate (PEFR) or forced expiratory volume in the first second of expiration (FEV ₁ ) helps characterize exacerbation severity. Severe exacerbations are characterized by a PEFR or FEV ₁ ≤50% of predicted or personal best, and alternative diagnoses should be considered when lung function is preserved. Failure of pharmacotherapy to improve expiratory flow significantly after the initial 30–60 minutes further predicts a refractory course requiring sustained treatment in the ED or hospitalization. Measurements of expiratory flow are not required in every patient. They are not likely to alter therapy in patients presenting with classic signs and symptoms of acute asthma, and obtaining peak expiratory flow measurements in a tenuous patient can worsen bronchospasm to the point of respiratory arrest.

Acid-base status

Arterial blood gases are indicated in patients with severe asthma exacerbations that are not responding significantly to initial therapy. Serial blood gases are generally not required unless the patient is mechanically ventilated. Although a venous blood gas can provide a reasonable approximation of arterial pH and a quick screen for hypercapnia, the poor correlation between arterial and venous partial pressure of carbon dioxide (PCO ₂ ) is a notable limitation of relying solely on venous blood gases in the critically ill patient with asthma. Hypoxemia and respiratory alkalosis are common in mild to moderate exacerbations. Eucapnia and hypercapnia suggest a severe exacerbation, but not necessarily the need for intubation, as even hypercapnic patients may respond to pharmacotherapy and/or noninvasive ventilation.

Renal compensation in response to respiratory alkalosis of adequate duration manifests as a normal anion gap metabolic acidosis. Lactic acidosis can result from increased work of breathing and the use of either high-dose nebulized or parenteral beta-agonist therapy. ^,

Chest radiography

Chest imaging rarely affects management in classic cases of asthma exacerbation. Indications for chest imaging include localizing signs on examination, concerns regarding barotrauma, questions regarding alternative diagnoses, and assessment of endotracheal tube position.

Emergency department disposition

Patients demonstrating an inadequate response to albuterol over the first 30–60 minutes of therapy in the ED invariably require hospital admission or prolonged treatment in the ED. Approximately one-third of patients fall into this “nonresponder” category ( Fig. 63.1 ). Along these lines, the Global Initiative for Asthma (GINA) report recommends hospital admission for patients presenting with a PEFR less than 50% of predicted or 50% of the patient’s personal best on presentation and <60% after initial treatment. Intensive care unit (ICU) admission is required for respiratory failure, the need for frequent albuterol treatments, deterioration despite treatment, fatigue, altered mental status, and cardiac complications. Patients with a PEFR between 60% and 80% of predicted or personal best after treatment may be eligible for discharge from the ED on appropriate therapy, although clinical judgment may favor admission, especially when the outpatient setting is suboptimal or noncompliance favors directly observed therapy. Patients with a good response can be discharged with appropriate maintenance therapy and instructions for follow-up.

Oxygen

Supplemental oxygen should be administered to maintain oxygen saturations above 90%. Doing so improves oxygen delivery to tissues, including the respiratory muscles, and reverses hypoxic pulmonary vasoconstriction. Oxygen further protects against desaturation consequent to beta-agonist-induced pulmonary vasodilation with increased blood flow to low $\stackrel{·}{V_A}/\stackrel{·}{Q}$ units.