Approach Considerations
The selection of laboratory studies depends on historical data and patient condition. Tests that should be performed in patients with status asthmaticus include the following:
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Complete blood cell (CBC) count
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Arterial blood gas (ABG) analysis
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Serum electrolyte levels
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Serum glucose levels
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Peak expiratory flow measurement
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Chest radiography
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Electrocardiogram (in older patients)
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Blood theophylline levels (if indicated)
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IgE level in selected patients
Chest Radiography
Obtain a chest radiograph to evaluate for pneumonia, pneumothorax, pneumomediastinum, congestive heart failure (CHF), and signs of chronic obstructive pulmonary disease, which would complicate the patient's response to treatment or reduce the patient's baseline spirometry values.
Chest radiography is indicated in patients who have an atypical presentation or in those who do not respond to therapy.
CBC Count
Obtain a CBC count and differential to evaluate for infectious causes (eg, pneumonia, viral infections such as croup), allergic bronchopulmonary aspergillosis, and Churg-Strauss vasculitis. When elevated, serum lactate levels (when obtained early at the onset of status asthmaticus) can correlate with improved lung function.
A CBC count and differential may demonstrate an elevated white blood cell count, with or without a shift to the left. The CBC count may also indicate a bacterial infection. However, beta-agonists and corticosteroids may result in demargination of white cells with an increase in the peripheral white cell count. [10, 11]
Arterial Blood Gas
An ABG value can be obtained to assess the severity of the asthma attack and to substantiate the need for more intensive care. However, the use of blood gas determination is controversial. The information generated by this measurement may be helpful in determining whether or not to intubate a patient with asthma. However, such decisions are usually made on the basis of clinical grounds in a patient who is either in respiratory arrest or impending respiratory arrest.
If a patient with acute asthma has adequate peripheral oxygen saturation, is receiving further therapy, and does not warrant immediate intubation, then the usefulness of blood gas data should be weighed against the potential pain and agitation that running this test may cause in a child. Improvement or deterioration in acute asthma can generally be followed clinically. Indwelling arterial catheters reduce the pain issue and generate highly reliable and reproducible information.
ABG determinations are indicated when the peak expiratory flow (PEF) rate or the forced expiratory volume in 1 second (FEV1) is less than or equal to 30% of the predicted value or when the patient shows evidence of fatigue or progressive airway obstruction despite treatment.
The 4 stages of blood gas progression in persons with status asthmaticus are as follows:
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Stage 1 - Characterized by hyperventilation with a normal partial pressure of oxygen (PO2)
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Stage 2 - Characterized by hyperventilation accompanied by hypoxemia (ie, a low partial pressure of carbon dioxide [PCO2] and low PO2)
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Stage 3 - Characterized by the presence of a false-normal PCO2; ventilation has decreased from the hyperventilation present in the second stage; this is an extremely serious sign of respiratory muscle fatigue that signals the need for more intensive medical care, such as admission to an ICU and, probably, intubation with mechanical ventilation.
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Stage 4 - Characterized by a low PO2 and a high PCO2, which occurs with respiratory muscle insufficiency; this is an even more serious sign that mandates intubation and ventilatory support.
Serum Electrolyte and Serum Glucose Levels
Serum electrolyte measurement, particularly of serum potassium levels, is important. Medications used to treat status asthmaticus may cause hypokalemia. A low pH may result in a transient elevation of potassium.
Serum glucose levels may become elevated from stress, the use of beta-agonist agents, such as epinephrine, and the use of corticosteroids. Because of poor stores, however, hypoglycemia may develop in younger children in response to stress.
Blood Theophylline Levels
Blood theophylline levels provide an important monitoring component in patients taking this medication (either at home or while hospitalized) and especially in patients who have received a bolus infusion of theophylline followed by continuous intravenous (IV) infusion. The volume of distribution of theophylline is 0.56 mg/L in children and adults. A dose of 1 mg/kg of theophylline raises the serum level by approximately 2 mg/dL.
If the patient has been receiving theophylline at home, obtain a serum theophylline level before therapy. Following a loading dose (if needed), obtain a serum level 30 minutes after the end of the infusion. For serum theophylline steady-state levels, obtain a serum sample at 24-36 hours in children younger than 6 months, at 12-24 hours for those aged 6 months to 12 years, and at 24 hours for children aged 12 years and older.
Factors that decrease theophylline clearance (increase levels) include cimetidine, erythromycin and other macrolide antibiotics, viral infections, cirrhosis, fever, propranolol, and ciprofloxacin.
Factors that increase theophylline clearance (decrease levels) are IV isoproterenol, phenobarbital, smoking, [12] phenytoin, and rifampin.
Pulmonary Function Testing
PEF, FEV1, and spirometry
Also see Pulmonary Function Testing.
The most important and readily available test to evaluate the severity of an asthma attack is the measurement of peak expiratory flow (PEF). PEF monitors are commonly available to patients for use at home and they provide asthmatic patients with a guideline for changes in lung function as they relate to changes in symptoms. In most patients with asthma, a decrease in peak flow as a percentage of predicted value correlates with changes in spirometry values.
Although the forced expiratory volume in one second (FEV1) is also used to monitor the degree of airway obstruction, in patients who are acutely ill, PEF monitoring is more commonly performed. Note that spirometry is more accurate (sensitive and reproducible).
According to the guidelines of the National Heart, Lung, and Blood Institute/National Asthma Education and Prevention Program, [13] hospitalization is generally indicated when the PEF or FEV1 after treatment is greater than 50%, but less than 70%, of the predicted value. Hospitalization in an ICU is dependent on the severity of symptoms, use of accessory muscles, and ABG results, as well as an FEV1 less than 50%.
A drop in the FEV1 to less than 25% of the predicted value indicates a severe airway obstruction. A patient with an FEV1 of greater than 60% of the predicted value may be treated in an outpatient setting, depending on the clinical situation. Some with associated fixed obstruction may have abnormal spirometry at baseline. Also, in very obese patients, FEV1 may be diminished. Thus, evaluation of the FEV1/FVC is quite helpful. However, if the patient's FEV1 or PEF rate drops to less than 50% of predicted, admission to the hospital is recommended.
Spirometry can be employed to monitor the progression of asthma. As the results indicate improvement, treatment may be adjusted accordingly. If a portable spirometry unit is not available, a PEF rate of 20% or less of the predicted value (ie, usually < 100 L/min) suggests severe airflow obstruction and impending respiratory failure.
Pulse oximetry
Pulse oximetry provides a continuous evaluation of oxygen saturation, which is vitally important because the primary cause of death in status asthmaticus is hypoxia.
The advantages of pulse oximetry are that pulse oximetry is readily available, it is noninvasive, it provides continuous monitoring, and it is a good indicator of hypoxemia resulting from a ventilation/perfusion mismatch.
The disadvantages of pulse oximetry are that movement artifact can be significant and the modality may provide an erroneous reading when pulsatile flow is inadequate (ie, shock with poor perfusion) or in the presence of anemia. Also, by the time desaturation occurs, there is significant reduction in oxygen and the use of a nebulized beta2 agonist can result in reduction in oxygen saturation secondary to increase in V/Q mismatch.
Other
Findings may be diminished in other pulmonary function tests (eg, maximum expiratory flow rate, mid-maximum expiratory flow rate, forced vital capacity). Functional residual capacity and residual volume increase because of air trapping, However, these tests require the child being in a body plethysmograph, which is impractical in the severely ill child.
Impulse Oscillometry Testing
In patients with reactive airways, Saadeh et al reported that impulse oscillometry detects false-negative spirometry values and provides a sensitive index of asthma control over the spectrum of mild to severe, persistent asthma. [14]
Patients can be shown the results of forced oscillation testing that occur with peripheral airway inflammation and obstruction. Review the test results with patients and show them the improvement with inhaled corticosteroids and the deterioration when they are not compliant with anti-inflammatory medications. This information may materially enhance patients' awareness of the need for continuing treatment, despite an absence of wheezing.
Technique
With forced oscillation testing using the impulse oscillometry system (IOS), patients are tested for 30-40 seconds during quiet breathing, without forced respiratory efforts. A small loudspeaker pushes "burps" of air into patients and pulls them back from the mouthpiece 5 times each second.
The measurement of airflow resistance during normal breathing requires no maximal forced expiratory efforts and does not subject patients to bronchoprovocation from forced expiration. Resistance is distributed between large airways and smaller, more peripheral airways, with distinct patterns attributable to each.
Bronchospasms and increased large-airway resistance appear as increases in resistance at higher (25-35 cycles/s) components of oscillation frequency. Additionally, a pattern of increased resistance with increasing airflow is typical of a large-airway bronchospasm. In such patients, resistance at the beginning and end of inspiration and expiration is at its minimum, with increased levels during midinspiration and midexpiration. In such patients, a deep inspiration is often followed by reflex bronchoconstriction and increased resistance for 30 seconds or more, signaling increased airway reactivity.
Peripheral airway inflammation and obstruction are signaled by increased resistance at low (5 cycles/s) oscillation frequencies that are decreased at higher oscillation frequencies (15 or 20 cycles/s). In association with the fall in resistance from 5-15 cycles per second, the magnitude of respiratory reactance in peripheral airway inflammation and obstruction increases.
Careful attention must be paid to whether patients have their lips fully closed around the mouthpiece. Patients with acute dyspnea may feel constrained when breathing through a mouthpiece and may reflexively open their mouths to increase airflow during late inspiration. This is analogous to flaring alae nasi with dyspnea and results in characteristic airflow leak patterns. This causes underestimation of true airflow resistance. IOS tests with such airflow leak patterns must be repeated after reassuring the patient and ensuring closure of the lips around the mouthpiece.
Histologic Findings
Autopsy results from patients who died from status asthmaticus of brief duration (ie, developed within hours) show neutrophilic infiltration of the airways. In contrast, results from patients who developed status asthmaticus over days show eosinophilic infiltration; this is more common and is associated with eosinophil up-regulation. Autopsy results also show extensive mucus production and severe bronchial smooth muscle hypertrophy. However, the predominant response, based on results from bronchoalveolar lavage studies, is eosinophilic in nature.
The eosinophil itself can lead to epithelial destruction through its own degrading products (eg, cationic proteins). This destruction can result in inflammation and, later, a neutrophilic response.
Staging
The 4 stages of status asthmaticus are based on ABG progressions in status asthma. Patients in stage 1 or 2 may be admitted to the hospital, depending on the severity of their dyspnea, their ability to use accessory muscles, and their PEF values or FEV1 after treatment (>50% but < 70% of predicted values).
Patients with ABG determinations characteristic of stages 3 and 4 require admission to an ICU. The PEF value or FEV1 is less than 50% of the predicted value after treatment.
Stage 1
Patients are not hypoxemic, but they are hyperventilating and have a normal PO2. Data suggest that to possibly facilitate hospital discharge, these patients may benefit from ipratropium treatment via a handheld nebulizer in the emergency setting as an adjunct to beta-agonists.
Stage 2
This stage is similar to stage 1, but patients are hyperventilating and hypoxemic. Such patients may still be discharged from the emergency department, depending on their response to bronchodilator treatment, but will require systemic corticosteroids.
Stage 3
These patients are generally ill and have a normal PCO2 due to respiratory muscle fatigue. Their PCO2 is considered a false-normal value and is a very serious sign of fatigue that signals a need for expanded care. This is generally an indication for elective intubation and mechanical ventilation, and these patients require admission to an ICU. Parenteral corticosteroids are indicated, as is the continued aggressive use of an inhaled beta2-adrenergic bronchodilator. These patients may benefit from theophylline.
Stage 4
This is a very serious stage in which the PO2 is low and the PCO2 is high, signifying respiratory failure. These patients have less than 20% of predicted lung function or FEV1 and require intubation and mechanical ventilation.
Patients in stage 4 should be admitted to an ICU. Switching from inhaled beta2-agonists and anticholinergics to metered-dose inhalers (MDIs) via mechanical ventilator tubing is indicated. Parenteral corticosteroids are essential, and theophylline may be added, as with patients in stage 3.
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Figure depicting antigen presentation by the dendritic cell, with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.
