Status asthmaticus

Status asthmaticus is considered a medical emergency. It is the extreme form of an

asthma exacerbation that can result in hypoxemia, hypercarbia, and secondary respiratory
failure.
Status asthmaticus is an acute exacerbation of asthma that remains unresponsive to initial
treatment with bronchodilators. Status asthmaticus can vary from a mild form to a severe
form with bronchospasm, airway inflammation, and mucus plugging that can cause
difficulty breathing, carbon dioxide retention, hypoxemia, and respiratory failure.
Patients report chest tightness, rapidly progressive shortness of breath, dry cough, and
wheezing and may have increased their beta-agonist intake (either inhaled or nebulized)
to as often as every few minutes.
Typically, patients present a few days after the onset of a viral respiratory illness, following
exposure to a potent allergen or irritant, or after exercise in a cold environment.
Frequently, patients have underused or have been underprescribed anti-inflammatory
therapy. Illicit drug use may play a role in poor adherence to anti-inflammatory therapy.

A study published in 2004 noted the number of patients with status asthmaticus requiring
intensive care admissions had declined over 10 years. The trend was toward less
advanced presentations. This may reflect improvements in medication compliance,
education, or access to medical care.Management goals for status asthmaticus are
(1) to reverse airway obstruction rapidly through the aggressive use of beta2-agonist
agents and early use of corticosteroids,
(2) to correct hypoxemia by monitoring and administering supplemental oxygen, and
(3) to prevent or treat complications such as pneumothorax and respiratory arrest.

Etiology
Exposure to an allergen or trigger causes a characteristic form of airway inflammation in
susceptible individuals, exemplified by mast cell degranulation, release of inflammatory
mediators, infiltration by eosinophils, and activated T lymphocytes. Multiple inflammatory
mediators may be involved, including interleukin (IL)3, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-
13, leukotrienes, and granulocyte-macrophage colony-stimulating factors (GM-CSFs).
These, in turn, incite involvement of mast cells, neutrophils, and eosinophils.
 Fi
gure depicting antigen presentation by the dendritic cell, with the lymphocyte and cytokine
response leading to airway inflammation and asthma symptoms.

Physiologically, acute asthma has two components: an early, acute bronchospastic aspect
marked by smooth muscle bronchoconstriction and a later inflammatory component
resulting in airway swelling and edema.
Early bronchospastic response
Within minutes of exposure to an allergen, mast cell degranulation is observed along with
the release of inflammatory mediators, including histamine, prostaglandin D2, and
leukotriene C4. These substances cause airway smooth muscle contraction, increased
capillary permeability, mucus secretion, and activation of neuronal reflexes. The early
asthmatic response is characterized by bronchoconstriction that is generally responsive to
bronchodilators, such as beta2-agonist agents.
Later inflammatory response
The release of inflammatory mediators primes adhesion molecules in the airway
epithelium and capillary endothelium, which then allows inflammatory cells, such as
eosinophils, neutrophils, and basophils, to attach to the epithelium and endothelium and
subsequently migrate into the tissues of the airway. Eosinophils release eosinophilic
cationic protein (ECP) and major basic protein (MBP). Both ECP and MBP induce
desquamation of the airway epithelium and expose nerve endings. This interaction
promotes further airway hyperresponsiveness in asthma. This inflammatory component
may even occur in individuals with mild asthma exacerbation.
Bronchospasm, mucus plugging, and edema in the peripheral airways result in increased
airway resistance and obstruction. Air trapping results in lung hyperinflation,
ventilation/perfusion (V/Q) mismatch, and increased dead space ventilation. The lung
becomes inflated near the end-inspiratory end of the pulmonary compliance curve, with
decreased compliance and increased work of breathing.
The increased pleural and intra-alveolar pressures that result from obstruction and
hyperinflation, together with the mechanical forces of the distended alveoli, eventually lead
to a decrease in alveolar perfusion. The combination of atelectasis and decreased
perfusion leads to V/Q mismatch within lung units. The V/Q mismatch and resultant
hypoxemia trigger an increase in minute ventilation.
Complications
In the early stages of acute asthma, hyperventilation may result in respiratory alkalosis.
This is because obstructed lung units (slow compartment) are relatively less numerous
than unobstructed lung units (fast compartment). Hyperventilation allows carbon dioxide
removal via the fast compartment. However, as the disease progresses and more lung
units become obstructed, an increase in the slow compartments occurs, resulting in
decreased ability for carbon dioxide removal and eventually causing hypercarbia.
Risk factors
Asthma results from a number of factors, including genetic predisposition and
environmental factors. Patients often have a history of atopy. The severity of asthma has
been correlated with the number of positive skin test results.
Gastroesophageal reflux disease is another risk factor for asthma, with studies indicating
that the reflux of gastric contents with or without aspiration can trigger asthma in
susceptible children and adults. Animal studies have shown that the instillation of even
minute amounts of acid into the distal esophagus can result in marked increases in
intrathoracic pressure and airway resistance. This response is thought to be due to vagal
and sympathetic neural responses.
Risk factors for asthma also include the following:
Viral infections
Air pollutants - Such as dust, cigarette smoke, and industrial pollutants
Medications - Including beta-blockers, aspirin, and nonsteroidal anti-inflammatory
drugs (NSAIDs)
Cold temperature
Exercise
CLINICAL MENIFESTATION
Wheezing Initially, wheezing is heard only during
expiration, but wheezing later occurs during expiration and
inspiration.
Chest hyperexpanded accessory muscles, particularly the
sternocleidomastoid, scalene, and intercostal muscles, are
used.
An inability to speak more than one or two words at a time
may also be observed in the later stages of an acute asthma
episode.
Ventilation/perfusion mismatch results in decreased oxygen
saturation and hypoxia.
Vital signs may show tachycardia and hypertension.
The patients level of consciousness may progress from
lethargy to agitation, air hunger, and even syncope and
seizures.

If untreated, prolonged airway obstruction and marked

increase in the work of breathing may eventually lead to
bradycardia, hypoventilation, and even cardiorespiratory
arrest.
Retractions (ie, intercostal and subcostal) and the use of
abdominal muscles may be observed.
unable to speak in full sentences.
Dehydration
Lethargic
Agitated
Comatose
Air hunger
Inspiratory wheezes and crackles
If tension pneumothorax develops, signs of tracheal
deviation to the opposite side, decreased or absent air entry
on the affected side, shift of the location of heart sounds,
and hypotension may be evident. Air leaks may also result
in pneumomediastinum and subcutaneous emphysema.
In moderate to severe status asthmaticus, abdominal
muscle use can cause symptoms of abdominal pain.
Pulsus paradoxus (a decrease in the systolic blood
pressure during inspiration) results from a decrease in
cardiac stroke volume with inspiration due to greatly
increased left-ventricular afterload. This increase is
generated by the dramatic increase in negative intrapleural
and transmural pressure in a patient struggling to breathe
against significant airways obstruction.
 Pulsus paradoxus of greater than 20 mm Hg correlates well
with the presence of severe airways obstruction (ie, forced
expiratory volume in 1 second [FEV1] < 60% predicted).

i. 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
ii. Complete blood count (CBC)
A CBC and differential may demonstrate an elevated white blood
cell count,. 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.
iii. Arterial blood gas (ABG)
An ABG value can be obtained to assess the severity of the
asthma attack and to substantiate the need for more intensive
care.
The 4 stages of blood gas progression in persons with
status asthmaticus are as follows:
Stage 1 - Characterized by hyperventilation with a normal
partial pressure of oxygen (PO2)
Stage 2 - Characterized by hyperventilation accompanied by
hypoxemia (ie, a low partial pressure of carbon dioxide
[PCO2] and low PO2)
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.
 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.
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 FEV 1 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 PCO 2 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 PO 2 is low and the PCO2
is high, signifying respiratory failure. These patients have less
than 20% 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 steroids are essential, and theophylline may be
added, as with patients in stage 3.
iv. Serum Electrolyte
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.
v. Serum Glucose Levels
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.
vi. Blood theophylline levels
Blood theophylline levels provide an important monitoring
component in patients taking theophylline (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.

vii. Pulmonary Function Testing

PEF and FEV1
The most important and readily available test to evaluate the
severity of an asthma attack is the measurement of 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 FEV1 is also used to monitor the degree of airway
obstruction, in patients who are acutely ill, peak flow monitoring
is more commonly performed.
According to the guidelines of the National Heart, Lung, and
Blood Institute/National Asthma Education and Prevention
Program, 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 FEV 1 of
greater than 60% of the predicted value may be treated in an
outpatient setting, depending on the clinical situation. However,
if the patient's FEV1 or PEF rate drops to less than 50% of
predicted, admission to the hospital is recommended.
Pulse oximetry and spirometry
Pulse oximetry and spirometry values should be used 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 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 V/Q mismatch.

Management
assessing the severity of an asthma attack, direct treatment
toward controlling bronchoconstriction and inflammation. Beta-
agonists, corticosteroids, and theophylline are mainstays in the
treatment of status asthmaticus. Sevoflurane, a potent
inhalation agent, was successful in a single case report in which
it was used when conventional treatment failed in a woman
aged 26 years.
Fluid replacement
Hydration, with intravenous normal saline at a reasonable rate,
is essential. Special attention to the patient's electrolyte status
is important.
Hypokalemia may result from either corticosteroid use or beta-
agonist use. Correcting hypokalemia may help to wean an
intubated patient with asthma from mechanical ventilation.
Hypophosphatemia may result from poor oral intake and is also
an important consideration when weaning such patients.
Antibiotics
The routine administration of antibiotics is discouraged. Patients
are administered antibiotics only when they show evidence of
infection (eg, pneumonia, sinusitis). In some situations, sinus
imaging using computed tomography (CT) scanning or plain
radiography may be essential to rule out chronic sinusitis.
Oxygen monitoring and therapy
Monitoring the patient's oxygen saturation is essential during
the initial treatment of status asthmaticus. Arterial blood gas
(ABG) values are usually used to assess hypercapnia during the
patient's initial assessment. Oxygen saturation is then
monitored via pulse oximetry throughout the treatment protocol.
Oxygen therapy is essential, with hypoxia being the leading
cause of death in children with asthma. Oxygen therapy can be
administered via a nasal canula or mask, although patients with
dyspnea often do not like masks. With the advent of pulse
oximetry, oxygen therapy can be easily titrated to maintain the
patient's oxygen saturation above 92% (>95% in pregnant
patients or those with cardiac disease).
In the event of significant hypoxemia, non-rebreathing masks
may be used to deliver as much as 98% oxygen. Tracheal
intubation and mechanical ventilation are indicated for
respiratory failure.
Chest tube placement
Chest tube placement may be necessary in the management of
pneumothorax.
Nitrate oxide
Nitrate oxide has been employed in a child with refractory
asthma. The future role of this therapy remains to be
determined.
Leukotriene modifiers
Leukotriene modifiers are useful for treating chronic asthma but
not acute asthma. This treatment may be beneficial if used via a
nebulizer, but it remains experimental. Most studies have
examined intravenous use, such as that by
ICU admission criteria
Indications for ICU admission include the following:
Altered sensorium
Use of continuous inhaled beta-agonist therapy
Exhaustion
Markedly decreased air entry
Rising PCO 2 despite treatment
Presence of high-risk factors for a severe attack
Failure to improve despite adequate therapy
Surgery
Status asthmaticus is generally managed by means of medical
therapy, with some exceptions. For example, thoracostomy is
indicated in pneumothoraces.
Some children may have asthma that is primarily exacerbated
by gastroesophageal reflux disease. Some patients can be
treated with a combination of antireflux (eg, proton pump
inhibitors) and histamine 2 (H2)receptor antagonist agents.
However, surgery, such as Nissen fundoplication, is occasionally
required.
Anesthesia support is needed if inhaled anesthetic agents are
considered for refractory severe intubated status asthmaticus.
If all other support modalities fail and extracorporeal membrane
oxygenation (ECMO) is required, surgical support for cannula
placement should take place at an established pediatric ECMO
center.

Diet
Some children with asthma may have episodes triggered by food
allergies. Consultation with a nutritionist may be necessary to
provide appropriate dietary management

Medication
The following agents are used in the pharmacologic treatment of status
asthmaticus:
Beta2-agonists - The first line of therapy in status asthmaticus
 Anticholinergics - Are believed to work centrally by suppressing
conduction in vestibular cerebellar pathways
Glucocorticosteroids - Among other therapeutic activities, can
decrease mucus production, improve oxygenation, reduce beta-
agonist or theophylline requirements, and activate properties that
may prevent late bronchoconstrictive responses to allergies and
provocation
Bronchodilators - Methylxanthines are weaker bronchodilators
than beta-agonists and have many adverse effects. Intravenous
magnesium sulfate can relax smooth muscle and hence cause
bronchodilation by competing with calcium at calcium-mediated
smooth muscle binding sites.

Enoximone is an imidazole phosphodiesterase III inhibitor that has

been used in patients with heart failure. In a limited report of eight
patients with status asthmaticus, and after exhausting maximal
treatment in six of these patients, enoximone was noted to be effective
via intravenous administration. It allowed the patients to improve
without the need of invasive treatment such as mechanical ventilation.
Its role in the future needs to be further investigated.