ACUTE EXACERBATION

OF ASTHMA
Dr. TROOB SULTANA
MO ER PSSHMC
Case:
• At 3 AM a 33-year-old known asthmatic presented in ER. As she is
brought in, you immediately notice that she is struggling to breathe.
Sweat pours from her face and body as her neck and chest heaves in
an attempt to inhale another breath. Her efforts are ultimately futile
as consciousness slips away and she becomes apneic.
• This is a case of a 33-year-old woman experiencing a severe asthma
attack. Respiratory arrest is imminent.
• The first priority in this patient’s management is addressing the ABCs
(airway, breathing, circulation). Based on this presentation, immediate
protection of her airway with rapid-sequence endotracheal
intubation is indicated. Simultaneously, this patient should be placed
on a cardiac monitor with automated blood pressure measurement,
establishment of IV access, and continuous pulse oximetry.
HIGH-RISK HISTORICAL FACTORS:
Prior intubation for asthma
• Prior hospitalization or ICU admission
• Frequent ED visits
• Frequent albuterol metered-dose inhaler (MDI) use
• Use of inhaled or oral corticosteroids at home
• Comorbid conditions (CAD, COPD, psychiatric)
• Low socioeconomic status
• Illicit drug use, especially inhaled cocaine
Trigger Factors:
Pathophysiology:
• Two distinct phases of asthma have been described.
• The early (or immediate) Phase of asthma consists of acute airway hyperresponsiveness
and reversible bronchoconstriction. Following allergen challenge, the lungs begin to
constrict within 10 minutes. Peak bronchoconstriction occurs at 30 minutes and either
spontaneously or with treatment resolves within 1 to 3 hours. With continued allergen
challenge or with refractory bronchoconstriction, this initial phase can progress into the
late phase of asthma.
• This late (or delayed) phase of asthma begins 3 to 4 hours after the allergen challenge and
constitutes the inflammatory component seen with acute asthma. Inflammatory cell
recruitment, bronchial edema, mucoserous secretion, and further bronchoconstriction all
play key roles in the development and propagation of late-phase asthma.
• Whereas beta-2 agonists target the immediate phase of asthma, corticosteroids target the
delayed phase.
Diagnosis:
• The evaluation of an asthmatic patient begins with the general
appearance of the patient. Those who are extremely anxious or
drowsy, unable to speak in full sentences secondary to respiratory
distress, or are using accessory muscles of inspiration (tripod
position/inability to lay supine) are at significant risk for rapid
decompensation. Additional worrisome features are signs of central
cyanosis, hypoxia (pulse oximetry <90%), significant tachypnea (>30
breaths per minute), tachycardia, diaphoresis, diffuse or absent
wheezing, and poor air entry on pulmonary examination.
• Bedside testing that measures peak expiratory flow rate (PEFR) or
fractional expiratory volume at 1 second (FEV1) are simple,
inexpensive ways of measuring the severity of airway obstruction and
are commonly used to monitor response to treatment in the ED.
• Severe asthma is defined as an FEV1 of less than 50% of predicted
(typically <200 L/min in an adult) or one’s own personal best
measurement.
• Formal diagnosis is made by spirometry
SUGGESTED INDICATIONS FOR
ANCILLARY TESTING:
ABG
• • To determine degree of hypercapnea or assess degree of deterioration in tiring patient not yet
sick enough to warrant endotracheal intubation.
CXR
• • Temp >38°C
• • Unexplained chest pain
• • Leukocytosis
• • Hypoxemia
• • Comorbidities/alternative diagnosis
ECG
• • Persistent tachycardia
• • Comorbidities/alternative diagnosis
Becker Asthma Score:
Management:
• Immediate priorities in the management of all asthma patients
include an initial assessment of the patient’s airway, breathing, and
circulation status. Patients in extremis require placement of
peripheral intravenous lines, continuous supplemental oxygen
therapy, and cardiac monitoring. While these interventions are
underway, the physician should ascertain a history, perform a physical
examination, and initiate appropriate therapy.
Oxygen, Compressed Air, and Heliox
• Oxygen should be provided to maintain a pulse oximetry reading of at
least 90% in adults and at least 95% in infants, pregnant women, and
patients with coexisting heart disease. Oxygen is often used as the
delivery vehicle for nebulized medications.
• Compressed air and helium-oxygen mixtures (heliox) can also be used.
Heliox mixtures produce a more laminar airflow and potentially deliver
nebulized particles to more distal airways, but they have not been
shown to consistently lead to improved ED outcomes for all asthmatic
patients. A systematic review concluded that heliox may be beneficial
only in patients who present with severe asthma that is refractory to
initial treatment.
Adrenergic Agents:
• Inhaled albuterol, through nebulization or metered-dose inhaler (MDI) with spacer
device, is the mainstay of treatment for acute asthma. Typically 2.5 to 5 mg (4 to 8
puffs )of albuterol is intermittently nebulized every 15 to 20 minutes for the first hour
of therapy and then repeated every 30 minutes thereafter for 1 to 2 more hours.
Continuous nebulization with higher doses (10-20 mg/h) of albuterol benefits severe
asthmatics.
• Beta-2 agonists bind pulmonary receptors and activate adenyl cyclase which results in
an increase in intracellular cyclic adenosine monophosphate (cAMP). This results in a
drop in myoplasmic calcium and subsequent bronchial smooth-muscle relaxation. In
addition, beta-2 agonists are thought to have some anti-inflammatory properties by
inhibiting inflammatory mediator release.
• Side effects of these agents are generally mild and include tachycardia, nervousness,
and shakiness or jitteriness.
• Although inhalation therapy is optimal, occasionally patients with
severe obstruction or who cannot tolerate inhalation therapy (eg,
children) are given subcutaneous administration of epinephrine or
terbutaline.
• Epinephrine is given in a dose of 0.3 to 0.5 mg subcutaneously every
20 minutes to a maximal combined total dose of 1 mg.
• Terbutaline is given 0.25 mg subcutaneously every 20 minutes up to a
maximum of three doses. Generally, terbutaline is preferable because
of its beta-2 selectivity and fewer cardiac side effects.
Anticholinergic Agents:
• When added to albuterol, anticholinergic agents lead to a modest improvement in pulmonary
function and decrease the admission rate in patients with moderate to severe asthma
exacerbations.
• Anticholinergics decrease intracellular cyclic guanosine monophosphate (cGMP)
concentrations, which reduce vagal nerve-mediated bronchoconstriction on medium- and
larger-sized airways. Additionally, anticholinergic agents may have some minor anti-
inflammatory properties that help to stabilize capillary permeability and inhibit mucous
secretion.
• The typical dose for ipratropium bromide is two puffs from a MDI with spacer device, or 0.5 mL
of the 0.02% solution. Anticholinergics can be combined with beta agonists in nebulization
devices and should be given to those not responding to initial beta-agonist therapy and those
with severe airway obstruction.
• Since there is little systemic absorption, inhaled anticholinergics are associated with few side
effects.
Corticosteroids:
• It is generally agreed that corticosteroids should be initiated early in the
treatment of the following cases:
• • Acute asthma in patients with moderate/severe asthma attack
• • Worsening asthma over many days (>3 days)
• • Mild asthma not responding to initial bronchodilator therapy or asthma
that develops despite daily inhaled corticosteroid use.
• Steroids act on the delayed phase of asthma and modulate the
inflammatory response. They have been shown to improve pulmonary
function, decrease the rate of hospital admission, and decrease the rate of
relapse in patients that receive them early in their ED treatment course.
• Oral administration of prednisone (dose 40-60mg) is usually preferred to intravenous
methylprednisolone (dose 125 mg), because it is less invasive and the effects are
equivalent. Intravenous steroids, however, should be administered to patients with
severe respiratory distress who are too dyspneic to swallow, patients who are
vomiting, or patients who are agitated or drowsy.
• For patients who will be discharged, a single intramuscular dose of
methylprednisolone (dose 160 mg) may be given when there is a history of medication
noncompliance.
• A 2-day course of oral dexamethasone (dose 16 mg) is also an option because it has
been shown to be equivalent to five days of prednisone.
• Alternative steroids include hydrocortisone 150 to 200 mg IV, dexamethasone 6 to 10
mg IV, or oral dexamethasone 0.6 mg/kg (maximum dose 16 mg) in pediatric patients.
Leukotriene Antagonists:
• The development of leukotriene antagonists represents an important
advancement in the treatment of chronic asthma. Studies involving zileuton
(Zyflo Filmtab), zafirlukast (Accolate), and montelukast (Singulair) demonstrate
that their daily use over the course of several months can lead to improvement
in pulmonary function and decrease in asthma symptomatology.
• However, the role of leukotriene antagonists in the treatment of acute asthma
exacerbations remains unclear.
• A randomized study of intravenous montelukast showed that it significantly
improved FEV when added to standard asthma therapy, but this improvement in
lung function did not translate to lower hospitalization rates. At this time,
asthma treatment guidelines recommend the use of leukotriene antagonists only
in the management of chronic asthma.
Magnesium:
• Although no benefit has been shown in mild to moderate asthmatics, magnesium sulfate given
intravenously at dosages of 2 to 4 g benefits asthmatics with severe airway obstruction.
• Magnesium is thought to compete with calcium for entry into smooth muscle, inhibit the release of
calcium from the sarcoplasmic reticulum, prevent acetylcholine release from nerve endings, and
inhibit mast cell release of histamine. Additionally, there is some evidence that magnesium may
directly inhibit smooth muscle contraction, but this is controversial.
• The onset of magnesium is quick and effects can be seen 2 to 5 minutes after initiation of therapy.
The effects are short lived and diminish quickly when the infusion is stopped.
• The dose of magnesium is 2 to 4 g IV in adults and 30 to 70 mg/kg IV in children given over 10 to 15
minutes.
• Magnesium has minimal side effects. The most commonly reported are hypotension, a flushing
sensation, and malaise.
• It is contraindicated in renal failure and in cases of hypermagnesemia as it can cause significant
muscle weakness.
Other Agents—Methylxanthines, Antibiotics:
• The marginal benefit, significant side effects, and difficulty achieving a
therapeutic dose of theophylline argue against its routine use in acute
asthma. A systematic review concluded that the addition of
aminophylline to treatment with beta agonists and glucocorticoids
improved lung function, but did not significantly reduce symptoms or
length of hospital stay. Therefore, methylxanthines are not
recommended in the treatment of acute asthma exacerbations.
• The routine administration of antibiotics has also not been shown to
decrease symptomatology in asthma patients without concurrent
bacterial lower respiratory infection or sinusitis.
Positive Pressure Ventilation:
• Positive pressure ventilation (PPV), with either invasive or noninvasive methods, is
indicated for patients with respiratory failure or impending failure who are not responsive
to therapy. Several studies have suggested that bi-level positive airway pressure (BiPAP)
may be beneficial in severe asthma exacerbations. For example, a randomized trial
enrolled severe asthmatics (defined as FEV1 <60% and RR>30) to receive BiPAP and found
significant improvements in pulmonary function and reduced rates of hospitalization.
• Severe asthmatics with impending respiratory failure should receive a trial of BiPAP prior
to being intubated. The BiPAP machine should be set at inspiratory pressure 8 to 15 cm
H2O and expiratory pressure 3 to 5 cm H2O.
• Patients who fail to improve over 30 to 60 minutes will likely require intubation.
Furthermore, contrary to prior teaching, a short trial (30 minutes) of BiPAP is considered
acceptable for mild to moderate altered level of consciousness attributed to hypercapnea.
• Immediate rapid-sequence endotracheal intubation should be reserved for
unconscious or near-comatose patients with respiratory failure.
• In an awake patient, an appropriate induction agent (eg, ketamine) and
paralytic agent (eg, succinylcholine) should be used prior to intubation.
Ketamine is the induction agent of choice because it stimulates the release
of catecholamines and causes relaxation of bronchial smooth muscle,
leading to bronchodilation. Numerous case reports have also
demonstrated that a ketamine infusion may be useful when severe
asthmatics fail to respond to conventional treatments.
• Ketamine is given as an intravenous bolus of 1 mg/kg, followed by a
continuous infusion of 0.5 to 2 mg/kg/h.
• Once an asthmatic patient is intubated, the ventilator should be set to promote the
goal of permissive hypercapnea which aims at minimizing dynamic hyperinflation (ie,
breath stacking or auto-PEEP [positive end-expiratory pressure]) with low tidal
volumes, and increased time for expiration, while limiting plateau pressures.
• It is critical to recognize that mechanically ventilated asthmatic patients are at high
risk for hyperinflation and auto-PEEP which can result in life threatening
complications such as tension pneumothorax or cardiac arrest. Suggested initial
settings are Assist Control mode at a respiratory rate of 8 to 10 breaths per minute,
tidal volume 6 to 8 mL/kg, no extrinsic PEEP, inspiratory-to-expiratory (I/E) ratio of
1:4, and an inspiratory flow rate of 80 to 100 L/min.
• To prevent barotrauma, plateau pressures should not exceed 30 cm H2O. Following
initiation of PPV, blood-gas analysis can be used to modify ventilator or BiPAP settings.
ADMISSION/DISCHARGE CRITERIA:
• Acute asthma is a heterogeneous condition and as such patients should be individualized when it comes to
disposition decisions. Patients who respond well to therapy by improved subjective and objective criteria (eg,
symptoms resolved, normal or near-normal pulmonary examination) are suitable candidates for discharge.
• Patients should be on room air and moving about the emergency department before finalizing the decision
to discharge the patient. An improvement of PEFR or FEV1 to greater than 70% predicted or personal best
can also be used as a sign of objective improvement.
• Hospital admission should be considered in patients that fail to respond to therapy (ie, PEFR or FEV1 < 50%
predicted) after 4 to 6 hours of treatment or patients with partial response to therapy (ie, PEFR or FEV1
between 50% and 70% predicted) and one or all of the following:
• 1. New-onset asthma
• 2. Multiple prior hospitalizations or ED visits
• 3. Have comorbidity from coronary artery disease
• 4. Have significant medical or social issues that impair access to health care, personal judgment, or
understanding of their disease.