Status Asthmaticus

Updated: Jun 17, 2020 Author Constantine K Saadeh, MD President,

Typically, patientsAllergy
presentARTS,
a fewLLP;
daysPrincipal
after the
Investigator, Amarillo Center for Clinical Research, Ltd
onset of a viral respiratory illness, following
exposure to a potent allergen or irritant, or
Practice Essentials
after exercise in a cold environment.
Status asthmaticus is considered a medical
Frequently, patients have underused or have
emergency. It is the extreme form of asthma
been underprescribed anti-inflammatory
exacerbation that can result in hypoxemia,
therapy. Illicit drug use may play a role in poor
hypercarbia, and secondary respiratory
adherence to anti-inflammatory therapy. (See
failure. In practice, the role of the physician is
Etiology and Presentation.)
to prevent this from happening through
patient compliance with controller
A study published in 2004 [2] noted the
medications (eg, steroid inhalers) in an
number of patients with status asthmaticus
outpatient setting.
requiring intensive care admissions had
declined over 10 years. The trend was toward
Patient education plays a very major role in
less advanced presentations. This may reflect
preventing recurrent attacks of status
improvements in medication compliance,
asthmaticus. In a study by Rice et al, [1]
education, or access to medical care.
inpatient asthma education was studied in
Nonetheless, concern has been raised more
children and adolescents following status
recently about an increase that has since been
asthmaticus. Subjects were enrolled in two
observed in the severity of asthma symptoms
groups. One group received the usual
and the need for more intensive care
posthospitalization instructions and the other
management. [3] (See Prognosis, Workup,
group received additional education by lay
Treatment, and Medication.)
asthma education volunteers. The group that
received the additional education had better
Treatment goals
compliance in the outpatient setting.
Management goals for status asthmaticus are
(1) to reverse airway obstruction rapidly
Background through the aggressive use of beta2-agonist
Status asthmaticus is an acute exacerbation of agents and early use of corticosteroids, (2) to
asthma that remains unresponsive to initial correct hypoxemia by monitoring and
treatment with bronchodilators. Status administering supplemental oxygen, and (3)
asthmaticus can vary from a mild form to a to prevent or treat complications such as
severe form with bronchospasm, airway pneumothorax and respiratory arrest.
inflammation, and mucus plugging that can
cause difficulty breathing, carbon dioxide Etiology
retention, hypoxemia, and respiratory failure. Exposure to an allergen or trigger causes a
(See Prognosis and Presentation.) characteristic form of airway inflammation in
susceptible individuals, exemplified by mast
Patients report chest tightness, rapidly cell degranulation, release of inflammatory
progressive shortness of breath, dry cough, mediators, infiltration by eosinophils, and
and wheezing and may have increased their activated T lymphocytes. Multiple
beta-agonist intake (either inhaled or inflammatory mediators may be involved,
nebulized) to as often as every few minutes. including interleukin (IL)–3, IL-4, IL-5, IL-6, IL-
(See Presentation.) 8, IL-10, and IL-13, leukotrienes, and
granulocyte-macrophage colony-stimulating

1
factors (GM-CSFs). These, in turn, incite neutrophils, and basophils, to attach to the
involvement of mast cells, neutrophils, and epithelium and endothelium and
eosinophils. (See the diagram below.) subsequently migrate into the tissues of the
airway. Eosinophils release eosinophilic

Physiologically, acute asthma has two cationic protein (ECP) and major basic protein
components: an early, acute bronchospastic (MBP). Both ECP and MBP induce
aspect marked by smooth muscle desquamation of the airway epithelium and
bronchoconstriction and a later inflammatory expose nerve endings. This interaction
component resulting in airway swelling and promotes further airway hyperresponsiveness
edema. in asthma. This inflammatory component may
even occur in individuals with mild asthma
Early bronchospastic response exacerbation.
Within minutes of exposure to an allergen,
mast cell degranulation is observed along with Bronchospasm, mucus plugging, and edema
the release of inflammatory mediators, in the peripheral airways result in increased
including histamine, prostaglandin D2, and airway resistance and obstruction. Air
leukotriene C4. These substances cause trapping results in lung hyperinflation,
airway smooth muscle contraction, increased ventilation/perfusion (V/Q) mismatch, and
capillary permeability, mucus secretion, and increased dead space ventilation. The lung
activation of neuronal reflexes. The early becomes inflated near the end-inspiratory
asthmatic response is characterized by end of the pulmonary compliance curve, with
bronchoconstriction that is generally decreased compliance and increased work of
responsive to bronchodilators, such as beta2- breathing.
agonist agents.
The increased pleural and intra-alveolar
Later inflammatory response pressures that result from obstruction and
The release of inflammatory mediators primes hyperinflation, together with the mechanical
adhesion molecules in the airway epithelium forces of the distended alveoli, eventually
and capillary endothelium, which then allows lead to a decrease in alveolar perfusion. The
inflammatory cells, such as eosinophils, combination of atelectasis and decreased
2
perfusion leads to V/Q mismatch within lung Medications - Including beta-blockers, aspirin,
units. The V/Q mismatch and resultant and nonsteroidal anti-inflammatory drugs
hypoxemia trigger an increase in minute (NSAIDs)
ventilation. Cold temperature
Exercise
Complications
In the early stages of acute asthma, Epidemiology
hyperventilation may result in respiratory Occurrence in the United States
alkalosis. This is because obstructed lung units Asthma affects up to 10% of the US
(slow compartment) are relatively less population. Prevalence has increased by 60%
numerous than unobstructed lung units (fast in all ages in the past two decades. A
compartment). Hyperventilation allows significant rise in hospitalization and asthma
carbon dioxide removal via the fast mortality rates has accompanied the
compartment. However, as the disease increased incidence.
progresses and more lung units become
obstructed, an increase in the slow Status asthmaticus is usually more common
compartments occurs, resulting in decreased among persons in low socioeconomic groups,
ability for carbon dioxide removal and regardless of race, as they have less access to
eventually causing hypercarbia. regular specialist medical care. [4] People who
live alone are particularly affected.
Risk factors
Asthma results from a number of factors, International occurrence
including genetic predisposition and The worldwide incidence of asthma is unclear
environmental factors. Patients often have a but is estimated to be about 20 million cases.
history of atopy. The severity of asthma has The dramatic rise in incidence has been
been correlated with the number of positive attributed, in part, to pollution and
skin test results. industrialization.

Gastroesophageal reflux disease is another Demographics

risk factor for asthma, with studies indicating In the United States, asthma prevalence is
that the reflux of gastric contents with or higher among children, women, blacks, and
without aspiration can trigger asthma in persons with reported income below the
susceptible children and adults. Animal federal poverty level.
studies have shown that the instillation of
even minute amounts of acid into the distal Prognosis
esophagus can result in marked increases in In general, unless a complicating illness such
intrathoracic pressure and airway resistance. as congestive heart failure or chronic
This response is thought to be due to vagal obstructive pulmonary disease is present,
and sympathetic neural responses. status asthmaticus has a good prognosis if
appropriate therapy is administered. A delay
Risk factors for asthma also include the in initiating treatment is probably the worst
following: prognostic factor. Delays can result from poor
Viral infections access to health care on the part of the patient
Air pollutants - Such as dust, cigarette smoke, or even delays in using corticosteroids.
and industrial pollutants

3
Patients with acute asthma should use with recent poorly controlled asthma, or with
corticosteroids early and aggressively. a history of prior intubation. One study links
Complications exposure to the common mold Alternaria
Complications of asthma can include the alternata and mortality in asthma.
following:
Cardiac arrest Patient Education
Respiratory failure or arrest Asthma is a chronic illness. Patients and their
Hypoxemia with hypoxic ischemic central families must be provided with a team that
nervous system (CNS) injury can offer education and follow-up care. Prior
Pneumothorax or pneumomediastinum to discharge, the team that provides asthma
Toxicity from medications education should meet with the family and
the patient to impart information regarding
Pneumothorax may complicate acute asthma maintenance, monitoring, and measures for
because of increased airway pressure or as a environmental control. Early identification of
result of mechanical ventilation. exacerbations and the importance of
Superimposed infection can also occur in adherence with therapy are paramount.
intubated patients. Patients may require a
chest tube for pneumothorax or aggressive Studies have also demonstrated the
antibiotic therapy for a superimposed importance of an asthma education plan.
infection. Guidelines regarding this literature have been
published. [8]
Mortality
The mortality rate from asthma has increased Patients require instruction in the appropriate
at an alarming rate. From 1993-1995, the use of inhalers, to be compliant with therapy,
overall annual age-adjusted death rate for and to practice stress-avoidance measures.
asthma increased 40%. The rise in the Stress factors (ie, triggers of asthma attacks)
mortality rate has been even higher among include pet dander, house dust, and mold.
blacks, among people living in poverty, and Strongly discourage patients from smoking,
among children aged 4 years or younger and this habit should be avoided at all costs.
those aged 9-16 years. More recently, asthma
mortality rates are trending lower. [6] History
Patients with status asthmaticus have severe
The mortality risk is also particularly high in dyspnea that has developed over hours to
patients who delay medical treatment, days. In most cases, there is a lead time of
especially treatment with systemic several days. [8] Frequently, these individuals
corticosteroids. Patients with other have a previous history of endotracheal
preexisting conditions (eg, restrictive lung intubation and mechanical ventilation,
disease, congestive heart failure, chest frequent emergency department visits, and
deformities) are at particular risk of death previous use of systemic corticosteroids.
from status asthmaticus. Patients who smoke
regularly have chronic inflammation of the If the physician does not obtain a thorough
small airways and are also at greater risk of history for a patient with asthma, he or she
death from status asthmaticus. Data also may not recognize a person with high risk
suggest higher mortality in persons of lower factors for acute and severe decompensation.
socioeconomic status, with psychiatric illness, This failure may prevent the aggressive use of

4
bronchodilators, corticosteroids, and ▪ History of syncope or seizures during
monitoring. When obtaining the history from acute exacerbation
a patient presenting with an acute ▪ Oxygen saturation below 92% despite
exacerbation of asthma, the following should supplemental oxygen
be determined: Subgroup of asthma patients who are poor
perceivers of dyspnea are a greater risk of
▪ Presence of current illness, such as intubation and death [9]
upper respiratory tract infection or
pneumonia Determine whether the patient has a severe
▪ History of chronic respiratory diseases asthma exacerbation without wheezing (i.e.,
(e.g., bronchopulmonary dysplasia, the silent chest). Such patients may have such
chronic lung disease of infancy) severe airway obstruction or be so fatigued
▪ Severe previous respiratory syncytial that they are unable to generate enough
virus (RSV) disease airflow to wheeze. This is an ominous sign of
▪ History of atopy impending respiratory failure.
▪ History of allergies
▪ Family history of asthma Physical Examination
▪ Presence of pets or smokers in the
Patients are usually tachypneic upon
home
examination and, in the early stages of status
▪ Known triggering factors
asthmaticus, may have significant wheezing.
▪ Home medications - Obtain a detailed
Initially, wheezing is heard only during
list of medications being taken at
expiration, but wheezing later occurs during
home and, if possible, their timing and
expiration and inspiration.
dosage
The chest is hyperexpanded, and accessory
Risk factors for developing severe or muscles, particularly the
persistent status asthmaticus include the sternocleidomastoid, scalene, and intercostal
following: muscles, are used. Later, as
bronchoconstriction worsens, the wheezing
▪ History of increased use of home may disappear, which may indicate severe
bronchodilator treatment without airflow obstruction.
improvement or effect
Normally, the difference in systolic blood
▪ History of previous intensive care unit
pressure between inspiration and expiration
(ICU) admissions, with or without
does not exceed 15 mm Hg. In patients with
intubation and mechanical ventilatory
severe asthma, a difference of greater than 25
support
mm Hg usually indicates severe airway
▪ Asthma exacerbation despite recent or
obstruction.
current use of corticosteroids
▪ Frequent emergency department An inability to speak more than one or two
visits and/or hospitalization (implies words at a time may also be observed in the
poor control) later stages of an acute asthma episode.
▪ Less than 10% improvement in peak Ventilation/perfusion mismatch results in
expiratory flow rate (PEFR) from decreased oxygen saturation and hypoxia.
baseline despite treatment Vital signs may show tachycardia and
hypertension. The peak flow rate should be

5
included in the vital signs in patients who are volume is compromised and hypotension and
able to cooperate and who are able to tolerate bradycardia may be observed.
the peak flow maneuver without significant
CNS status ranges from wide awake to
distress.
lethargic and from agitated to comatose. As
The patient’s level of consciousness may hypoxemia progresses, lethargy progresses to
progress from lethargy to agitation, air agitation caused by air hunger. As more lung
hunger, and even syncope and seizures. If units become obstructed, hypoxemia worsens
untreated, prolonged airway obstruction and and hypercarbia develops. Both hypoxemia
marked increase in the work of breathing may and hypercarbia can lead to seizures and
eventually lead to bradycardia, coma and are late signs of respiratory
hypoventilation, and even cardiorespiratory compromise.
arrest.
Examination of the respiratory system
General examination
Wheezing occurs from air moving through
The peak flow rate is a standard measure of narrowed, obstructed airways. Thus
airflow obstruction and is relatively simple to exhalation results in turbulent airflow and
perform. Most patients with more than a mild produces wheezes. Although asthma is the
exacerbation of asthma have hypoxia and most common cause of wheezing, anything
decreased oxygen saturation due to V/Q that causes airway obstruction and narrowing
mismatch. Oxygen saturation may increase that results in turbulent airflow may generate
following the use of bronchodilators wheezes. Therefore, not all wheezing is
secondary to an increase in V/Q mismatch. asthma.
Some patients prefer to remain seated and
Auscultation often reveals bilateral expiratory
leaning forward, rather than assuming a
and possibly inspiratory wheezes and crackles.
supine position.
Air entry may or may not be diminished or
Retractions (i.e., intercostal and subcostal) absent, depending on severity. Remember,
and the use of abdominal muscles may be the silent chest may herald impending
observed in patients with status asthmaticus. respiratory failure in a patient too obstructed
The use of accessory muscles has been shown or fatigued to generate wheezing.
to correlate with the severity of airflow
If tension pneumothorax develops, signs of
obstruction. An abnormally prolonged
tracheal deviation to the opposite side,
expiratory phase with audible wheezing can
decreased or absent air entry on the affected
be observed. Patients with moderate to
side, shift of the location of heart sounds, and
severe asthma are often unable to speak in full
hypotension may be evident. Air leaks may
sentences.
also result in pneumomediastinum and
Dehydration can occur in adults, but is subcutaneous emphysema.
observed less frequently than in children.
In moderate to severe status asthmaticus,
Cardiovascular symptoms may include abdominal muscle use can cause symptoms of
tachycardia or hypertension in mild to abdominal pain.
moderate asthma. With worsening
Pulsus paradoxus (a decrease in the systolic
hypoxemia, hypercarbia, marked air trapping,
blood pressure during inspiration) results
and hyperinflation, the ventricular stroke
from a decrease in cardiac stroke volume with
inspiration due to greatly increased left-
6
ventricular afterload. This increase is the onset of status asthmaticus) can correlate
generated by the dramatic increase in with improved lung function.
negative intrapleural and transmural pressure
A CBC count and differential may demonstrate
in a patient struggling to breathe against
an elevated white blood cell count, with or
significant airways obstruction. Pulsus
without a shift to the left. The CBC count may
paradoxus of greater than 20 mm Hg
also indicate a bacterial infection. However,
correlates well with the presence of severe
beta-agonists and corticosteroids may result
airways obstruction (ie, forced expiratory
in demargination of white cells with an
volume in 1 second [FEV1] < 60% predicted).
increase in the peripheral white cell count.
Approach Considerations [10, 11]
The selection of laboratory studies depends Arterial Blood Gas
on historical data and patient condition. Tests
An ABG value can be obtained to assess the
that should be performed in patients with
severity of the asthma attack and to
status asthmaticus include the following:
substantiate the need for more intensive care.
▪ Complete blood cell (CBC) count However, the use of blood gas determination
▪ Arterial blood gas (ABG) analysis is controversial. The information generated by
▪ Serum electrolyte levels this measurement may be helpful in
▪ Serum glucose levels determining whether or not to intubate a
▪ Peak expiratory flow measurement patient with asthma. However, such decisions
▪ Chest radiography are usually made on the basis of clinical
▪ Electrocardiogram (in older patients) grounds in a patient who is either in
▪ Blood theophylline levels (if indicated) respiratory arrest or impending respiratory
▪ IgE level in selected patients arrest.
Chest Radiography If a patient with acute asthma has adequate
peripheral oxygen saturation, is receiving
Obtain a chest radiograph to evaluate for
further therapy, and does not warrant
pneumonia, pneumothorax, pneumo-
immediate intubation, then the usefulness of
mediastinum, congestive heart failure (CHF),
blood gas data should be weighed against the
and signs of chronic obstructive pulmonary
potential pain and agitation that running this
disease, which would complicate the patient's
test may cause in a child. Improvement or
response to treatment or reduce the patient's
deterioration in acute asthma can generally
baseline spirometry values.
be followed clinically. Indwelling arterial
Chest radiography is indicated in patients who catheters reduce the pain issue and generate
have an atypical presentation or in those who highly reliable and reproducible information.
do not respond to therapy.
ABG determinations are indicated when the
CBC Count peak expiratory flow (PEF) rate or the forced
expiratory volume in 1 second (FEV1) is less
Obtain a CBC count and differential to
than or equal to 30% of the predicted value or
evaluate for infectious causes (e.g.,
when the patient shows evidence of fatigue or
pneumonia, viral infections such as croup),
progressive airway obstruction despite
allergic bronchopulmonary aspergillosis, and
treatment.
Churg-Strauss vasculitis. When elevated,
serum lactate levels (when obtained early at

7
The 4 stages of blood gas progression in patients for use at home and they provide
persons with status asthmaticus are as asthmatic patients with a guideline for
follows: changes in lung function as they relate to
changes in symptoms. In most patients with
Stage 1 - Characterized by hyperventilation
asthma, a decrease in peak flow as a
with a normal partial pressure of oxygen (PO2)
percentage of predicted value correlates with
Stage 2 - Characterized by hyperventilation
changes in spirometry values.
accompanied by hypoxemia (i.e., a low partial
pressure of carbon dioxide [PCO2] and low Although the forced expiratory volume in one
(PO2) second (FEV1) is also used to monitor the
Stage 3 - Characterized by the presence of a degree of airway obstruction, in patients who
false-normal PCO2; ventilation has decreased are acutely ill, PEF monitoring is more
from the hyperventilation present in the commonly performed. Note that spirometry is
second stage; this is an extremely serious sign more accurate (sensitive and reproducible).
of respiratory muscle fatigue that signals the
According to the guidelines of the National
need for more intensive medical care, such as
Heart, Lung, and Blood Institute/National
admission to an ICU and, probably, intubation
Asthma Education and Prevention Program,
with mechanical ventilation.
[13] hospitalization is generally indicated
Stage 4 - Characterized by a low PO2 and a
when the PEF or FEV1 after treatment is
high PCO2, which occurs with respiratory
greater than 50%, but less than 70%, of the
muscle insufficiency; this is an even more
predicted value. Hospitalization in an ICU is
serious sign that mandates intubation and
dependent on the severity of symptoms, use
ventilatory support.
of accessory muscles, and ABG results, as well
Serum Electrolyte and Serum Glucose Levels as an FEV1 less than 50%.
Serum electrolyte measurement, particularly A drop in the FEV1 to less than 25% of the
of serum potassium levels, is important. predicted value indicates a severe airway
Medications used to treat status asthmaticus obstruction. A patient with an FEV1 of greater
may cause hypokalemia. A low pH may result than 60% of the predicted value may be
in a transient elevation of potassium. treated in an outpatient setting, depending on
the clinical situation. Some with associated
Serum glucose levels may become elevated
fixed obstruction may have abnormal
from stress, the use of beta-agonist agents,
spirometry at baseline. Also, in very obese
such as epinephrine, and the use of
patients, FEV1 may be diminished. Thus,
corticosteroids. Because of poor stores,
evaluation of the FEV1/FVC is quite helpful.
however, hypoglycemia may develop in
However, if the patient's FEV1 or PEF rate
younger children in response to stress.
drops to less than 50% of predicted, admission
to the hospital is recommended.

Pulmonary Function Testing Spirometry can be employed to monitor the

progression of asthma. As the results indicate
PEF, FEV1, and spirometry
improvement, treatment may be adjusted
The most important and readily available test accordingly. If a portable spirometry unit is
to evaluate the severity of an asthma attack is not available, a PEF rate of 20% or less of the
the measurement of peak expiratory flow predicted value (ie, usually < 100 L/min)
(PEF). PEF monitors are commonly available to

8
suggests severe airflow obstruction and treatment (>50% but < 70% of predicted
impending respiratory failure. values).
Pulse oximetry Patients with ABG determinations
characteristic of stages 3 and 4 require
Pulse oximetry provides a continuous
admission to an ICU. The PEF value or FEV1 is
evaluation of oxygen saturation, which is
less than 50% of the predicted value after
vitally important because the primary cause
treatment.
of death in status asthmaticus is hypoxia.
Stage 1
The advantages of pulse oximetry are that
pulse oximetry is readily available, it is Patients are not hypoxemic, but they are
noninvasive, it provides continuous hyperventilating and have a normal PO2. Data
monitoring, and it is a good indicator of suggest that to possibly facilitate hospital
hypoxemia resulting from a discharge, these patients may benefit from
ventilation/perfusion mismatch. ipratropium treatment via a handheld
nebulizer in the emergency setting as an
The disadvantages of pulse oximetry are that
adjunct to beta-agonists.
movement artifact can be significant and the
modality may provide an erroneous reading Stage 2
when pulsatile flow is inadequate (ie, shock
This stage is similar to stage 1, but patients are
with poor perfusion) or in the presence of
hyperventilating and hypoxemic. Such
anemia. Also, by the time desaturation occurs,
patients may still be discharged from the
there is significant reduction in oxygen and
emergency department, depending on their
the use of a nebulized beta2 agonist can result
response to bronchodilator treatment, but
in reduction in oxygen saturation secondary to
will require systemic corticosteroids.
increase in V/Q mismatch.
Stage 3
Other
These patients are generally ill and have a
Findings may be diminished in other
normal PCO2 due to respiratory muscle
pulmonary function tests (eg, maximum
fatigue. Their PCO2 is considered a false-
expiratory flow rate, mid-maximum expiratory
normal value and is a very serious sign of
flow rate, forced vital capacity). Functional
fatigue that signals a need for expanded care.
residual capacity and residual volume
This is generally an indication for elective
increase because of air trapping, However,
intubation and mechanical ventilation, and
these tests require the child being in a body
these patients require admission to an ICU.
plethysmograph, which is impractical in the
Parenteral corticosteroids are indicated, as is
severely ill child.
the continued aggressive use of an inhaled
Staging beta2-adrenergic bronchodilator. These
patients may benefit from theophylline.
The 4 stages of status asthmaticus are based
on ABG progressions in status asthma. Stage 4
Patients in stage 1 or 2 may be admitted to the
This is a very serious stage in which the PO2 is
hospital, depending on the severity of their
low and the PCO2 is high, signifying
dyspnea, their ability to use accessory
respiratory failure. These patients have less
muscles, and their PEF values or FEV1 after
than 20% of predicted lung function or FEV1

9
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