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DEFINITION :

CLASSIFICATION OF ASTHMA
Classifying asthma severity and initiating treatment in youths greater than or equal to 12 years of
age and adults
Classification of asthma severity (12 years of age)
Components of severity
Persistent
Intermittent
Mild
Moderate
Severe
Impairment
>2 days/week
Throughout
Symptoms
2 days/week
Daily
but not daily
the day
Normal
>1x/week
Often
FEV1/FVC: Nighttime awakenings 2x/month
3-4x/month
but not
7x/week
nightly
LASSIFICA Short-acting beta >2 days/week
2
TION-19 yr
but not daily,
Several times
85 percent agonist use for
2 days/week and not more Daily
per day
symptom control (not
than 1x on any
20-39 yr 80 prevention of EIB)
day
percent
Interference with
Minor
Some
Extremely
None
normal activity
limitation
limitation
limited
40-59 yr 75 Lung function
Normal FEV1 FEV1 80
FEV1 >60 FEV1 <60
percent
between
percent
but <80
percent
exacerbations predicted
percent
predicted
60-80 yr 70
predicted
percent
FEV1 >80
FEV1/FVC
FEV1/FVC
percent
reduced >5

predicted
FEV1/FVC
normal

Risk

Exacerbations
requiring oral
systemic
corticosteroids

Recommended step for initiating


treatment

normal

FEV1/FVC
percent
reduced 5
percent

0-1/year (see
2/year (see footnote)
footnote)
Consider severity and interval since last exacerbation
Frequency and severity may fluctuate over time for
patients in any severity category
Relative annual risk of exacerbations may be related to
FEV1
Step 3
Step 4 or 5
And consider short course
Step 1
Step 2
of oral systemic
corticosteroids
In 2-6 weeks, evaluate level of asthma control that is
achieved and adjust therapy accordingly.

Pathophysiology of Asthma
Genetic and environmental factors
IgE-dependent mechanisms important
Triggers are non-specific (eg cold, exercise) or specific (dust mites, pollen, animal danders), stress
or
emotion
Two patterns:
Acute severe asthma, symptoms over hours/days on background of poor control. Slower to respond
to
treatment, ?due to greater contribution from mucous and bronchial wall inflammation
Hyperacute: very quick, less common, younger male patients, high bronchial reactivity to triggers
responding quicker to bronchodilators
Respiratory impact:
work of breathing from airways resistance and compliance (due to hyperinflation). Mechanical
disadvantage due to lung volume close to TLC respiratory muscle failure with ventilation
V/Q mismatch due to airway narrowing: further increases MV requirements work of breathing
Haemodynamic effects:
Inspiratory pleural pressures as low as -35 cmH20 venous return RV volume LV
volume
Hypoxic pulmonary vasoconstriction, acidosis, lung volume RV afterload LV preload
Negative intrapleural pressures LV afterload
Pulsus paradoxus: in systolic blood pressure during inspiration of > 10 mmHg (typically 15 25
mmHg, normal = 5 mmHg)

Key Pathophysiology
Chronic inflammatory disorder of the airways is associated with bronchoconstriction, airway
edema, and hyperresponsiveness.
Chronic inflammation can lead to persistent changes and remodeling including subbasement
membrane fibrosis, mucus hypersecretion, epithelial cell injury, smooth muscle hypertrophy, and
angiogenesis.
This is characterized by inflammatory cell infiltration with neutrophils, eosinophils,
lymphocytes, and mast cells and their mediators.
It leads to recurrent episodes of wheezing, coughing, chest tightness, widespread reversible
variable airflow obstruction, and V/Q mismatch.
In asthmatic crisis, air trapping can lead to high FRC, total lung capacity (TLC), and residual
volume, with tidal breathing occurring near the upper limit of TLC.
Often the hyperinflation is dynamic and the respiratory system is often not able to reach
equilibrium at the end of expiration before the next inspiration begins resulting in an auto-PEEP.
This leads to increased work of breathing, decreased preload, and an accentuation of the normal
inspiratory reduction in LV stroke volume.
In asthma, airflow limitation is intermittent and reversible, whereas in chronic obstructive
pulmonary disease (COPD) there is progressive airflow obstruction.
Exposure to certain allergens and respiratory viruses early in life is thought to play a role in
development of asthma.

Differential Diagnosis

COPD
Bronchitis
Left ventricular failure
Upper airway obstruction
Pulmonary embolism
Anaphylaxis
Management and Treatment
Most patients will have a history of gradually worsening shortness of breath though some, often
younger patients, may develop life-threatening bronchospasm and respiratory failure over minutes
to hours.
Wheezing is detectable with mild and moderate obstruction, but as airflow decreases, may
disappear with severe obstruction.

Danger signs that signify impending ventilatory failure include the following:
Deteriorating mental status
Silent chest
Arterial pulses paradoxus > 15 to 20 mmHg
Severe hyperinflation
CO2 retention/elevated PaCO2
Acidosis
Cyanosis
Hypoxemia
A compensated asthma attack will usually illicit mild hyperventilation resulting in a slight
respiratory alkalosis and mild to moderate hypoxemia.
The two most common modalities for monitoring asthma are peak expiratory flow rate (PEFR)
that can be performed at the bedside and spirometry that cannot be done at the bedside.
PEFR is the greatest flow velocity that can be obtained during a forced exhalation starting with
lungs fully inflated and can be measured with a handheld device.
This is an effort-dependent measurement reliable only when effort is maximal.
FEV1/FVC < 0.7 indicates airflow obstruction.

TABLE 11.3 Typical Physical Examination and Laboratory Findings in Asthma by Severity

Respiratory
arrest
imminent

Finding

Mild

Moderate

Severe

Breathless

Walking

Talking

At rest

Can lie down

Prefers
sitting

Hunched
forward

Speaks in

Sentences

Phrases

Words

Alertness

May be
agitated

Usually
agitated

Usually
agitated

Respiratory
rate

Increased

Increased

>30
breaths/
min

Accessory
muscle use
and
retractions

Usually not

Usually

Usually

Wheeze

Moderate,
often endexpiratory

Loud

Usually
loud

Absent

Pulse

<100

100-120

>120

Bradycardia

Drowsy or
confused

(beats/min)

(<60)

Pulsus
paradoxus

Absent (<10
mm Hg)

May be
present
(10-25 mm
Hg)

Often
present
(>25 mm
Hg)

PEF
%predicted

>80%

60%-80%

<60%

PaO2

Normal

>60 mm
Hg

<60 mm
Hg

PaCO2

<45 mm Hg

<45 mm
Hg

>45 mm
Hg

SaO2

>95%

91%-95%

<90%

Absence
suggests
respiratory
muscle fatigue

PEF, peak expiratory flow.

Though much of the pharmacologic therapy used in acute asthma exacerbations focuses on the
treatment of bronchospasm, attenuating the inflammatory response, edema, and secretions is also
important.
Management of an acute attack often includes both inhaled and oral therapy.
Aerosol drug therapy can be administered via metered-dose-inhaler or nebulizer.
The dose of bronchodilators delivered via nebulizer is much greater than that delivered via MDI
(but the bronchodilator response is the same with both devices as long as the MDI is used with a
spacer).
In the breathless or obtunded patients, nebulization is generally preferred.
Short-acting B2 agonists are often used as first-line treatment for their bronchodilating
properties.

The effect is achieved by cyclic adenosine monophosphate (cAMP)-mediated relaxation of


bronchial smooth muscles via B2 adrenergic receptors.
Side effects include tachycardia, tremors, hyperglycemia, hypokalemia, hypomagnesemia, and
hypophosphatemia.
Albuterol is the most frequently used inhaled B2 agonist.
Levalbuterol (Xopenex) is a highly selective B2 agonist that may cause less tachycardia.
It is important to remember that in patients with severe bronchospasm inhaled therapy may not
be able to reach its intended site of action.
Long-acting B2 agonists may be used in treatment of chronic asthma but do not have a place in
the management of the acute asthma exacerbation.
Parental B2 agonists such as epinephrine or terbutaline may be given (SQ or IV) in patients who
do not respond to inhaled B2 agnosists.
Inhaled anticholinergics (ipratropium bromide) are often used in combination with B2
agonists and may be especially useful as adjunctive treatment in the setting of B2-mediated
tachycardia, when B2 tachyphylaxis is suspected, or when there is a vagally mediated cause of
bronchospasm.
Effect is achieved through blockade of muscarinic receptors in the airways.
Side effects include dry mouth, blurred vision, and/or mental status changes.
Anisocoria associated with nebulized ipratropium is not an infrequent finding.
Corticosteroids should be given to virtually every patient requiring ICU admission for asthma.
They act via complex and incompletely understood pathways to help reduce inflammation, thin
secretions, and block components of the allergic response.
The beneficial effects will not be seen for 4 to 6 hours after a bolus dose of steroids with
maximum effect at 12 to 16 hours.
Side effects include mood and sleep disturbance, hyperglycemia, immunosuppression, and
neuromyopathy.
Methylxanthines (theophylline and amniophyline) may be used cautiously as adjunctive therapy
in resistant cases or for status asthmaticus for their bronchodilatory effects.
True mechanism is not fully known; however, bronchodilation is thought to be mediated by
inhibition of phosphodiesterase III and phosphodiesterase IV.
These drugs have a small therapeutic index and can cause heart failure, arrhythmias, agitation,
seizures, and hepatic disease.
As critically ill patients often cannot report symptoms of toxicity like nausea and abdominal
pain, serum levels must be monitored.
The benefit of magnesium sulfate therapy in refractory asthma is unclear.
Its mild bronchodilatory properties are likely due to blockade of calcium channels and resulting
smooth muscle relaxation.
Side effects are minimal and usually limited to mild muscle weakness.
Volatile anesthetics may be used for refractory severe status asthmaticus.
Secretion retention is a problem in asthma and can result in mucus plugs; therefore, airway
humidification and chest physiotherapy can be helpful.
Inhaled mucolytics such as acetylcysteine and hypertonic NaHCO3 may irritate the airways and

thus must be used in close conjunction with an inhaled bronchodilator.


Noninvasive ventilation, though not as clearly helpful as with COPD exacerbation, may help the
fatigued patient until pharmacologic therapy with bronchodilators and corticosteroids can take
effect.
Patients must be carefully monitored and those who deteriorate despite aggressive treatment
should be intubated.
Ventilator management must take into consideration gas trapping and resulting hyperinflation,
which if not managed appropriately can lead to hemodynamic compromise and barotrauma with
resulting pneumothorax or pneumomediastinum.
Decreased ventilation, increased expiratory time, and decreasing resistance can all help to
decrease hyperinflation.
Measured auto-PEEP in the intubated patient may be falsely low if extensive plugging prevents
airways from communicating with the circuit.
Adding some PEEP may possibly improve bronchodilator penetration and open occluded
airways though careful attention must be paid to peak and mean alveolar pressures.

Aerosol Drug Therapy


Drug aerosols play a major role in the management of obstructive airways diseases. There are two
basic designs for aerosol generators in clinical medicine: the jet nebulizer and the metered-dose
inhaler. The operation of these devices is illustrated in Figure 24.1

Jet Nebulizer
The pneumatic or jet nebulizer uses the same principle as the air-entrainment device in Figure
22.5 (see page 435). A high-pressure gas source (e.g., 50 psi from a wall outlet) is passed through a
narrow opening in the nebulizer, creating a high-velocity (jet) stream of gas that is passed over the
opening of a narrow tube submerged in a drug solution. The gas jet draws the drug solution up the
tube (by creating viscous drag) and then pulverizes the solution to create an aerosol spray that is
inhaled by the patient. Standard jet nebulizers have a reservoir volume of 36 mL, and can
completely aerosolize the reservoir volume in less than 10 minutes (6). A larger version (with a
reservoir volume >200 mL) is available for continuous aerosol therapy (see later).
FIGURE 24.1 Devices used for aerosol drug therapy. See text for explanation.
LUNG DEPOSITION: Although small-volume nebulizers can completely aerosolize a drug
solution, only a fraction of the drug aerosol reaches the lungs. This is demonstrated in Table 24.1,
which shows the distribution of aerosolized albuterol with different aerosol generator systems (7).
When the nebulizer is used, most of the aerosol impacts on the delivery apparatus or is exhaled, and
only 12% of the intended dose reaches the lungs. Inefficient drug delivery is a characteristic feature
of aerosol drug therapy, and is not specific for the jet nebulizer.

Metered-Dose Inhaler
A metered-dose inhaler (MDI) operates like a canister of hair spray. The MDI has a pressurized
canister that contains a drug solution with a boiling point below room temperature. When the
canister is squeezed between the thumb and fingers, a valve opens that releases a fixed volume of
the drug solution. The liquid immediately vaporizes when it emerges from the canister, and a liquid
propellant in the solution creates a high-velocity spray.

LUNG DEPOSITION: The spray emerging from an MDI can have a velocity in excess of 30 meters
per second (over 60 miles per hour) (8), and when this high-velocity spray is delivered directly into
the mouth, most of the spray impacts on the posterior wall of the oropharynx and is not inhaled.
This inertial impaction is reduced by using a spacer device or holding chamber to reduce the
velocity of aerosol delivery. The influence of a holding chamber on drug delivery is shown in Table
24.1. When the MDI is used alone, 80% of the drug aerosol is deposited in the oropharynx, but
when a holding chamber is used with the MDI, drug deposition in the mouth is almost completely
eliminated, and the drug dose reaching the lungs is doubled. Results like this are the reason
that holding chambers are recommended for all bronchodilator treatments with MDIs (6).
Table 24.1 Distribution of Inhaled Albuterol by Delivery System

Nebulizer vs. Metered-Dose Inhaler


One of the notable features of aerosol drug therapy is the equivalent bronchodilator responses
produced by nebulizers and MDIs despite a large difference in drug dosage. This is demonstrated
in Figure 24.2, which compares the bronchodilator response to albuterol delivered by nebulizer and
MDI (with a holding chamber) in patients with acute exacerbation of asthma (9). There is no
difference in the response in each of the 3 treatments. Using the distribution patterns in Table 24.1,
the dose of albuterol deposited in the lungs in Figure 24.2 would be 12% of 2.5 mg or 250 g for
the nebulizer and 20% of 360 g or 72 g for the MDI with holding chamber. Thus, there is a 3.5fold difference in drug dose in the airways, yet the bronchodilator responses are equivalent.

Laboratory Findings
Pulmonary Function Findings
OBJECTIVE MEASURES OF AIRFLOW OBSTRUCTION
In addition to clinical assessments, a peak expiratory flow rate (PEFR), the forced expiratory volume in 1 second (FEV 1 ), or both should be measured in all patients with asthma who can tolerate
such measurements. These measurements can be safely performed in many patients, typically at
presentation and 15 to 20 minutes after bronchodilator therapy; however, one should defer such
measurements if severe airway obstruction or overt respiratory failure is clinically obvious, as these

maneuvers can precipitate cardiopulmonary arrest in severe asthmatic patients. Although a PEFR
< 150 L/minute or an FEV 1 < 1 L confirms severe obstruction, comparison to baseline pulmonary
function measurements (if available) is even more helpful. A PEFR 33% to 50% of predicted
indicates a severe asthma exacerbation, whereas PEFR < 25% predicted before treatment or < 40%
predicted after treatment suggests a life-threatening exacerbation and identifies patients requiring
hospitalization and admission to an ICU.
A decrease in airflow rates throughout the vital capacity is the cardinal pulmonary function abnormality during an asthmatic episode. The peak expiratory flow rate (PEFR), the forced expiratory volume in the first second
(FEV 1 ), and the maximal mid-expiratory flow rate (MMEFR) are all
decreased in asthma (Chapter 85). In severe asthma, dyspnea may be so
severe as to prevent the patient from performing a complete spirogram. In
this case, if 2 seconds of forced expiration can be recorded, useful values for
PEFR and FEV 1 can be obtained. Gradation of attack severity (Table 87-1)
must be assessed by objective measures of airflow; no other methods yield
accurate and reproducible results. As the attack resolves, the PEFR and the
FEV 1 increase toward normal together while the MMEFR remains substantially depressed; as the attack resolves further, the FEV 1 and the PEFR may
normalize while the MMEFR remains depressed (see Fig. 87-1). Even when
the attack has resolved clinically, residual depression of the MMEFR is not
uncommon; this depression may resolve during a prolonged course of treatment. If the patient is able to cooperate such that more complete measurements of lung function can be made, lung volume measurements made
during an attack demonstrate an increase in both total lung capacity and
residual volume; the changes in total lung capacity and residual volume
resolve with treatment. Because of the extra cooperation needed for this
testing, it is not advised during an acute asthmatic event; such testing is,
however, indicated between episodes of asthma.
Exhaled NO
The fraction of NO in the exhaled air (Fe NO ) is elevated in patients with
asthma. Although the exact concentration considered elevated will vary
with the details of the technique, a concentration of 15 parts per billion is a
convenient and reliable level that can be used to distinguish normal subjects
from patients with untreated asthma. However, the measurement of exhaled
nitric oxide has not been shown to be of value in the day-to-day management
of asthma. 1-3
Arterial Blood Gases
Table 140.8 Staging Severe Asthma Crisis by Arterial Blood Gases
Stage 1Stage 2
Stage 3
Stage 4
Stage 5
PaCO Normal PaCO2
PaCO2
Normal
PaCO2
(respiratory
failure)
PaO2 NormalNormal PaO2
PaO2 (hyperventilation PaO2
PaO2. These
(hyperventilation has is now unable to
(inspiratory
findings indicate
led to normalization of compensate totally for a fatigue is now an impending
PaO2).
widened P(A a)O2.
prominent).
respiratory arrest.
Blood gas analysis need not be undertaken in individuals with mild asthma.
If the asthma is of sufficient severity to merit prolonged observation, however,

blood gas analysis is indicated; in such cases, hypoxemia and hypocapnia are
the rule. With the subject breathing ambient air, the Pao 2 is usually between
55 and 70 mm Hg and the Paco 2 between 25 and 35 mm Hg. At the onset
of the attack, an appropriate pure respiratory alkalemia is usually evident;
with attacks of prolonged duration, the pH returns toward normal as a result
of a compensatory metabolic acidemia. A normal Paco 2 in a patient with
moderate to severe airflow obstruction is reason for concern because it may
indicate that the mechanical load on the respiratory system is greater than
can be sustained by the ventilatory muscles and that respiratory failure is
imminent. When the Paco 2 increases in such settings, the pH decreases
quickly because the bicarbonate stores have become depleted as a result of
renal compensation for the prolonged preceding respiratory alkalemia.
Because this chain of events can take place rapidly, close observation is indicated for asthmatic patients with normal Paco 2 levels and moderate to
severe airflow obstruction.
Other Blood Findings
Asthmatic subjects are frequently atopic; thus, blood eosinophilia is common
but not universal. In addition, elevated serum levels of immunoglobulin E
(IgE) are often documented; epidemiologic studies indicate that asthma is
unusual in subjects with low IgE levels. If indicated by the patients history,
specific radioallergosorbent tests, which measure IgE directed against specific
offending antigens, can be conducted. In rare instances during severe asthma
attacks, serum concentrations of aminotransferases, lactate dehydrogenase,
muscle creatine kinase, ornithine transcarbamylase, and antidiuretic hormone
may be elevated.
Radiographic Findings
The chest radiograph of a subject with asthma is often normal. Severe asthma
is associated with hyperinflation, as indicated by depression of the diaphragm
and abnormally lucent lung fields. Complications of severe asthma, including
pneumomediastinum or pneumothorax, may be detected radiographically. In
mild to moderate asthma without adventitious sounds other than wheezing,
a chest radiograph need not be obtained; if the asthma is of sufficient severity
to merit hospital admission, a chest radiograph is advised.
Electrocardiographic Findings
The electrocardiogram, except for sinus tachycardia, is usually normal in
acute asthma. However, right axis deviation, right bundle branch block, P
pulmonale, or even ST-T wave abnormalities may arise during severe asthma
and resolve as the attack resolves.
Sputum Findings
The sputum of the asthmatic patient may be either clear or opaque with a
green or yellow tinge. The presence of color does not invariably indicate
infection, and examination of a Gram-stained and Wright-stained sputum
smear is indicated. The sputum often contains eosinophils, Charcot-Leyden
crystals (crystallized eosinophil lysophospholipase), Curschmanns spirals
(bronchiolar casts composed of mucus and cells), or Creola bodies (clusters
of airway epithelial cells with identifiable cilia that, in fresh samples, can
often be seen to beat), which can affect color without the presence of
infection.
DIAGNOSIS
Differential Diagnosis
Asthma is easy to recognize in a young patient without comorbid medical
conditions who has exacerbating and remitting airway obstruction accompa-

nied by blood eosinophilia. A rapid response to bronchodilator treatment is


usually all that is needed to establish the diagnosis. However, in the patient
with cryptic episodic shortness of breath, an elevated Fe NO can help establish
a diagnosis of asthma. However, in the absence of an elevated Fe NO , other
causes of wheezing (see Table 83-3 in Chapter 83) should be investigated.
TREATMENT :

Table 48.2 Objective Assessment of Airway Obstruction After Initial Intensive Therapy
PEFR or FEV1
Interpretation
70% predicted
Good response
40% but 69% predicted
Incomplete response
< 40% predicted
Poor response
FEV1, forced expired volume in 1 second; PEFR, peak expiratory flow
rate.
Medication

Dose

Comments

2.55 milligrams every


20 min for three doses,
then 2.510 milligrams
every 14 h, as needed,
or 1015 milligrams/h as
continuous nebulization.

Only selective B2 agonists are


recommended. For optimal delivery,
dilute aerosols to minimum of 3 mL at
gas flow of 68 L/min. Use large volume
nebulizers for continuous administration.
May mix with ipratropium nebulizer
solution.

Inhaled B2 Agonists
Albuterol
Nebulizer solution (0.63
milligram/3 mL, 1.25
milligrams/3 mL, 2.5
milligrams/3 mL, 5.0
milligrams/mL)

MDI (90 micrograms/puff) 48 puffs every 20 min In mild-to-moderate exacerbations, MDI


up to 4 h, then every 14 plus valved holding chamber is as
h as needed.
effective as nebulized therapy with
appropriate administration technique and
coaching by trained personnel.
Bitolterol
Nebulizer solution (2
milligrams/mL)

See albuterol dose.

Has not been studied in severe asthma


exacerbations. Do not mix with other
drugs.

MDI (370
micrograms/puff)

See albuterol MDI dose.

Has not been studied in severe asthma


exacerbations.

1.252.5 milligrams
every 20 min for three
doses, then 1.255
milligrams every 14 h,
as needed.

Levalbuterol administered in one half the


milligram dose of albuterol provides
comparable efficacy and safety. Has not
been evaluated by continuous
nebulization.

Levalbuterol (R-albuterol)
Nebulizer solution (0.63
milligram/3 mL, 1.25
milligrams/3 mL)

Medication

Dose

Comments

MDI (45 micrograms/puff) See albuterol MDI dose.


Pirbuterol
MDI (200
micrograms/puff)

See albuterol MDI dose.

Has not been studied in severe asthma


exacerbations.

Systemic (Injected) B2 Agonists


Epinephrine
1:1000 (1 milligram/mL)

0.30.5 milligram every


20 min for three doses
SC.

No proven advantage of systemic therapy


over aerosol.

0.25 milligram every 20


min for three doses SC.

No proven advantage of systemic therapy


over aerosol.

Terbutaline
(1 milligram/mL)

Anticholinergics/Combinations
Ipratropium bromide
Nebulizer solution (0.25
milligram/mL)

0.5 milligram every 20


May mix in same nebulizer with
min for three doses, then albuterol. Should not be used as first-line
as needed.
therapy; should be added to SABA
therapy for severe exacerbations. The
addition of ipratropium has not been
shown to provide further benefit once the
patient is hospitalized.

MDI (18 micrograms/puff) Eight puffs every 20 min, Should use with valved holding chamber
as needed, up to 3 h.
and face mask for children <4 y. Studies
have examined ipratropium bromide MDI
for up to 3 h.
Ipratropium with albuterol
Nebulizer solution (each 3- 3 mL every 20 min for
mL vial contains 0.5
three doses, then as
milligram ipratropium
needed.
bromide and 2.5 milligrams
albuterol.)

May be used for up to 3 h in the initial


management of severe exacerbations. The
addition of ipratropium has not been
shown to provide further benefit once the
patient is hospitalized.

MDI (each puff contains 18 Eight puffs every 20 min Should use with valved holding chamber
micrograms ipratropium
as needed up to 3 h.
and face mask for children <4 y.
bromide and 90 micrograms
of albuterol.)
Systemic Corticosteroids

Applies to all three corticosteroids for


oral medications.

Prednisone

For inpatients: oral


"burst," use 4080
milligrams/d in one or
two divided doses until
PEF reaches 70% of
predicted or personal
best.

For outpatients: oral "burst," use 4060


milligrams in single or two divided doses
for 510 d.

Methylprednisolone

IV: 1 milligram/kg every For outpatients: a single IM dose of 150

Medication

Prednisolone

Dose

Comments

46 h.

milligrams depot methylprednisolone


may be used.23

12 milligrams/kg/d for
510 d; may be divided
twice daily.

More frequently used over prednisone in


children due to increased palatably of
available liquid formulations.

Albuterol is the most widely used short-acting 2-agonist for the acute management of asthma
(1,14,15). Aerosolized albuterol has a rapid onset of action (less than 5 minutes), and a
bronchodilator effect that lasts 25 hours (18).Levalbuterol is the R-enantiomer of albuterol (a more
active form of the drug) that is equally effective at half the dose. However, clinical studies have not
shown an advantage with levalbuterol over albuterol (1,14).

Aerosol Regimens
The following regimens of aerosolized albuterol are recommended for acute exacerbations of
asthma (1,14,15):
1. The initial treatment involves up to three 20-minute treatments using 2.5 to 5 mg albuterol by
nebulizer or 48 puffs (90 mg al-buterol per puff) by MDI with a holding chamber. Nebulizer
delivery is preferred for patients with severe airflow obstruction (1), even though there is no
evidence that nebulizers produce better bronchodilator responses than MDIs in acute asthma (19).
2. If further therapy is needed, albuterol can be given hourly for up to 3 hours, or can be given by
continuous nebulization using doses of 515 mg/hr. Continuous aerosol therapy is popular, and may
be more effective than intermittent aerosol therapy in patients with severe airflow obstruction (20).
3. For patients who are admitted to the hospital, albuterol (2.55 mg by nebulizer or 48 puffs by
MDI) is given every 46 hours for the duration of the hospital stay.

Parenteral Therapy
For the rare asthmatic patient who does not tolerate bronchodilator aerosols (usually because of
excessive coughing) parenteral therapy can be given using subcutaneous epinephrine (0.3 to 0.5 mg
every 20 minutes for 3 doses) or subcutaneous terbutaline (0.25 mg every 20 minutes for 3 doses)
(1). However, it is important to emphasize that parenteral -agonist therapy is not more effective
than aerosol therapy, and is more likely to produce unwanted side effects (21).

Side Effects
High-dose aerosol therapy with 2-agonists can produce a number of side effects, including
tachycardia, tremors, hyperglycemia, and a decrease in serum potassium, magnesium, and
phosphate levels (22,23). Cardiac ischemia has been reported, but is rare (22). The decrease in
serum potassium is the result of a -Receptor-mediated shift of potassium into cells. This effect is
notable because large doses of inhaled 2-agonists (e.g., 20 mg albuterol) have been used for the
acute management of hyperkalemia (24). (Note: This is not a favored treatment for hyperkalemia
because of the side effects of high-dose 2-agonists.)

Anticholinergic Agents
Anticholinergic agents offer only marginal benefits in acute asthma, and their use is restricted to
combination therapy with short-acting 2-agonists for severe exacerbations, and only for the first 3
4 hours of management (1,25). The only anticholinergic agent approved for use in the United States
is ipatropium bromide, a derivative of atropine that blocks muscarinic receptors in the airways. The
dose in acute asthma is 0.5 mg (which can be mixed with albuterol in the nebulizer) every 20
minutes for 3 doses, then as needed, or 8 puffs (18 g per puff) by MDI every 20 min as needed for
up to 3 hours (1). Systemic absorption is minimal, and there is little risk of anticholinergic side
effects (e.g., tachycardia, dry mouth, blurred vision, urinary retention). Ipatropium has no proven
benefit beyond the first few hours of management, and it should be discontinued in patients who are
admitted for continued asthma management (1).

Corticosteroids
Corticosteroids are considered a staple in the management of both acute and chronic asthma. In
acute asthma, the bulk of evidence shows that corticosteroids accelerate the rate of resolution and
reduce the risk of relapses (26), although not all studies show a benefit from corticosteroids (27,28).
The following features of steroid therapy deserve mention:
1. There is no difference in efficacy between oral and intravenous steroids (26,29).
2. The beneficial effects of steroids are often not apparent until 12 hours after therapy is started
(29), so steroid therapy will not influence the clinical course of asthma in the emergency
department.
3. There is no apparent dose-response curve for steroids (29), and no evidence that doses above 100
mg of prednisone daily (or equivalent doses of other steroids) provide added benefit in acute asthma
(26).
4. A 10-day course of steroids can be stopped abruptly without a tapering dose (26,30).

Regimen in Acute Asthma


The National Asthma Education Program includes the following recommendations for
corticosteroid therapy in acute exacerbations of asthma (1).

1. Steroids are recommended for all patients who do not show a satisfactory response after one or
two bronchodilator treatments.
2. Oral steroids are recommended for patients who can tolerate oral medications.
3. The recommended dose is 4080 mg daily of prednisone (for oral therapy)
or methylprednisolone (for intravenous therapy) in one or two divided doses, which is continued
until there is evidence of satisfactory resolution.
4. If the duration of therapy is less than 10 days, there is no need for a steroid taper.
5. Inhaled corticosteroids can be started at any time during treatment of an acute exacerbation of
asthma, and are continued after systemic steroids are discontinued to reduce the risk of relapses.

Mechanism of Action?
Acute asthma is considered more of an inflammatory condition than a bronchospastic condition, and
the beneficial effects of steroids are attributed to their anti-inflammatory actions. However, as
shown in Table 24.3, dexamethasone is the most potent anti-inflammatory corticosteroid, yet it is
not recommended for the treatment of asthma. This is either an oversight, or it raises questions
about the mechanism of action of steroids in asthma.
Table 24.3 Comparison of Therapeutic Corticosteroids

Steroid Myopathy
An acute myopathy has been reported in ventilator-dependent asthmatic patients treated with highdose steroids and neuromuscular blocking agents (31). Unlike the traditional steroid myopathy,
which is characterized by proximal muscle weakness, this condition involves both proximal and
distal muscles, and is often associated with rhabdomyolysis. The muscle weakness can be
prolonged (although it usually resolves) and can hamper weaning from mechanical ventilation.
Because of the risk of this myopathy, it seems wise to avoid neuromuscular paralysis whenever
possible in steroid-treated ventilator-dependent asthmatic patients.

Additional Considerations
The following are some additional considerations for the management of acute asthma:
1. Asthma exacerbations are often triggered by viral infections, and empiric antibiotic therapy is not
advised the absence of a treatable infection (1).
2. Intravenous magnesium (2 grams over 20 min) has mild bronchodilator effects (possibly as a
result of calcium channel blockade), and can be used as an adjunctive measure for severe

exacerbations of asthma (1). However, magnesium administration has no impact on the clinical
course of acute asthma (32).
3. An arterial blood gas is advised for patients who do not show a satisfactory response to
bronchodilators in the emergency department. A normal PCO2 in acute asthma indicates severe
airflow obstruction, and warrants admission to the ICU.
4. Intubation and mechanical ventilation can be problematic in acute exacerbations of asthma; this
aspect of management is described in the final section of the chapter.

Management of Asthma (cicm NOTES 2013)


Oxygen:
Humidified O2 so sats > 90%
Emerging evidence of harms of hyperoxia in some: pulmonary hypoxic vasoconstriction,
worsening V/Q mismatch PCO2
Short acting -agonists:
Salbutamol (relatively 2 selective), terbutaline, isoprenaline, epinephrine
Cause smooth-muscle mediated bronchodilation and may mucosal oedema
MDIs with spacer may be better than nebuliser (< 10% reaches the lungs even under ideal
conditions)
Little evidence to support IV -agonists they have a theoretical advantage of reaching less
ventilated
lung. Typical dose is 5 20 g/min. SE include: tachycardia, arrhythmia, hypertension, hypotension,
tremor, hypokalaemia, hyperglycaemia, and lactic acidosis (in 70% after 2 4 hours, reaching 4
12
mmol/l and may significantly add to respiratory acidosis and distress. Settles 4 6 hours after
cessation)
Anticholinergics:
parasympathetic-mediated cholinergic bronchomotor tone bronchodilation
Ipratropium is a quaternary derivative of atropine. Clear evidence of incremental benefit and few
extra side-effects
Respiratory 115
Optimal dose unknown recommended 0.5 mg every 2 6 hours (although more frequent initial
dosing has been used)
Corticosteroids:
responsiveness, inflammatory cell response, mucus secretion
Effects within 6 12 hours, oral as effective as IV, no benefit from > 800 mg hydrocortisone/day. If
IV, convert to declining oral dose of prednisone 0.5 mg/kg within 4 7 days
Use inhaled steroids from day 1
SE: hyperglycaemia, K, hypertension, acute psychosis, myopathy, infection risk (including
legionella, PCP and varicella)
Aminophylline:
Conflicting studies. Inferior bronchodilator with narrow therapeutic range and frequent side-effects
(headache, nausea, vomiting, restlessness; arrhythmias and seizures at serum levels > 0.2 mmol/l or
40
mg/l). Structural and pharmacological similarity to caffeine
Cochrane Review 2012 (Travers et al) of 11 studies comparing 350 patients getting IV -agonists or
aminophylline. No difference in outcomes. More side effects with aminophylline
Initial loading dose of 3 mg/kg (omitted if already taking theophylline) and infuse at 0.5 mg/hour.
Reduce if cirrhosis, CHF, COPD or if on cimetidine, erythromycin or antiviral vaccines. Check drug
levels every 24 hours (30 80 mol/l)

Magnesium Sulphate: blocks ca channels smooth-muscle relaxation. 5 10 mmol slowly over 20


mins.
SE: hypotension, flushing, sedation, weakness, arreflexia, respiratory depression and arrhythmias at
high
levels
Non-established rescue treatments:
Adrenaline: No benefit found over salbutamol. Really need central access
Heliox: 70% helium, 30% oxygen. Mixed results from trials. Reduces gas density and turbulence
with airflow resistance
Volatile anaesthetic
Ketamine: may cause some bronchodilation. Useful induction agent (1 2 mg/kg). SE secretions,
hyperdynamic cardiovascular response and hallucinations (reduced with benzodiazepines)
Leukotriene Antagonists: evidence in chronic asthma. Only some evidence in acute asthma
Inhaled mucolytics: no benefit and may worsen obstruction
Antibiotics: not unless there is evidence of infection
Sedation: clear association with avoidable deaths
Ventilation of Asthma
Dynamic Hyperinflation:
Incomplete exhalation traps gas lungs dont return to FRC progressive accumulation of
trapped gas
Equilibrium reached when small airway calibre and lung elastic recoil increase enough to allow
tidal volume to be exhaled
Adaptive in mild obstruction as allows desired Vt to be achieved
Trapped gas exerts a positive pressure on the alveoli = PEEPi or autoPEEP. Measured PEEPi
underestimates true PEEPi as less obstructed airways only remain in communication with major
airways
during exhalation. See Measurement of Lung Mechanics73
As airway obstruction worsens, static hyperinflation rises (due to airway closure)
NIV:
Theoretical advantages:
External PEEP overcomes PEEPi and therefore reduces the inspiratory threshold work of
breathing
Augmentation of inspiration with NIV work of breathing
Shorter inspiratory time less DHI
Inspiratory augmentation + PEEP airspace opening V/Q mismatch
Experimental works suggest main effect is to unload inspiratory muscles
No large RCTs
Contraindications: LOC, haemodynamic instability, inability to protect airway and clear secretions
and high risk of aspiration
Start at CPAP of 5 and IPAP of 13 15 aiming for respiratory rate < 25 and exhaled tidal volume of
7
ml/kg. Favourable response is usually apparent within the first hour
Complications: nasal bridge ulceration, mask discomfort, nasal congestion, gastric insufflation,
aspiration, hypotension and pneumothorax (lower risk than with intubation)
116 CICM Study Notes
Invasive Ventilation:
A patient who complains of exhaustion is likely to need intubation
Intubate with largest tube possible and bag slowly ( 8 10 /min)
Initial settings:
Minute ventilation < 115 ml/kg/min (< 8 l/min in a 70 kg patient), eg Vt of 5 7 ml/kg and RR of
10 12, short inspiratory time to ensure expiratory time > 4 secs (requires volume-controlled
inspiratory flow rate of 70 100 l/min)

Results in a high peak airway pressure but will lower DHI and Pplat and reduce barotrauma
PEEP will further increase lung volume and should not be used initially
This will cause hypoventilation respiratory acidosis respiratory distress so will need heavy
sedation
If significant hypotension treat by reducing the respiratory rate ( DHI) and intravascular
loading
Assessing DHI:
Measure Pplat: airway pressure after transient expiratory pause at the end of inspiration
Intrinsic PEEP is the airway pressure during occlusion of expiratory flow at the end of expiration
If transient rate reduction to 4 6 breaths/min for 2 4 min or during apnoea of 60 seconds
significant increase in BP and in CVP then DHI has been suppressing circulation
Adjusting ventilation:
Use minimum amount of hypoventilation to achieve a safe level of DHI in association with less
sedation and minimal of no use of NMBAs
Adjust ventilation based on DHI, not on PaCO2 or pH. If Pplat > 25 then reduce rate. If Pplat is
low then rate or reduce sedation and allow spontaneous breathing
Hypercapnia is usually well tolerated. No evidence of benefit from bicarbonate but some
recommend for PCO2 < 7.1 to reduce acidaemia induced respiratory distress
Pressure support of 10 16 cmH2O when obstruction improves. CPAP of 3 7 will assist
ventilator triggering and work of breathing
Complications of invasive ventilation:
Risks pulmonary hyperinflation and aggravation of bronchospasm
Hypotension cause by sedation, DHI, pneumothoaces, arrhythmias or hypovolaemia
PEA arrest: a small number of patients can rapidly develop excessive DHI during initial
uncontrolled mechanical ventilation. Immediately disconnect from the ventilator (apnoea) for 60
seconds or hypoventilate 2 3 breaths/min to diagnose and improve
Pneumothorax: as soon as it is suspected, reduce RR to protect the other lung from over-inflation.
Always insert intercostal catheter by blunt dissection.
Acute necrotising myopathy: in patients who also receive NMBAs or very deep sedation
(exacerbated by steroids). Weakness, EEG evidence of myopathy, and CK. Muscle biopsy
diagnostic

Ventilator Strategies
The goal of management in status asthmaticus is to unload the respiratory muscles, correct
hypoxemia, provide adequate ventilation, and minimize lung injury, particularly from DHI, while
treating the underlying airway inflammation and bronchoconstriction.
Noninvasive Ventilation

Although the concept of treating acute asthma (an air trapping disease) with additional
airway pressure at the end of expiration seem counterintuitive, a number of studies have indicated
that it may actually reduce work of breathing during exacerbations of bronchospasm. Bilevel
positive airway pressure (BiPAP) also enhances bronchodilatory effect of albuterol.

Data regarding the use of noninvasive positive pressure ventilation (NIPPV) in severe
asthma are limited.

NIPPV with either continuous positive airway pressure or BiPAP may be considered
as initial treatment of patients presenting to the emergency department with status asthmaticus who
are alert, cooperative, and able to protect their airways while tolerating a full face mask.
P.73

Initial BiPAP settings, inspiratory positive airway pressure (IPAP) of 8 and expiratory

positive airway pressure (EPAP) of 5, and adjusted promptly to achieve patient comfort and
compliance and decrease work of breathing (decreased respiratory rate, increased tidal volume)
without exceeding IPAP of 15 and EPAP of 5.

Aerophagia with subsequent vomiting and aspiration is potential complications of


NIPPV, and patients should be closely monitored and kept fasting.

Clinical improvement after initiation of NIPPV (decreased respiratory rate, improved


air movement, decreased PaCO2) should be documented shortly after initiation of NIPPV and
pharmacologic treatment (within 30 minutes).

Lack of improvement should prompt the clinician to the need for intubation and
mechanical ventilation. Once deemed necessary, intubation should not be delayed.

instability.

NIPPV is contraindicated in patients with decreased mental status and hemodynamic

TABLE 11.4 Initial Ventilator Settings in Status Asthmaticus


Parameter
Setting
Mode
Volume controlled
Minute ventilation
10 L
Tidal volume
7-8 mL/kg
Respiratory rate
12-14 breaths/min
Inspiratory flow rate
60-80 LPM
PEEP
0-5 cm H2O
FiO2
Titrate to keep SpO2 >90%
LPM, liters per minute; PEEP, positive end-expiratory pressure.
Invasive Ventilation
Ventilator strategies should concentrate on allowing adequate expiratory time to avoid DHI and
barotrauma. Mechanical ventilation with volume-controlled ventilation is preferable. Suggested
initial settings are listed in Table 11.4. A lung protective and permissive hypercapnia strategy should
be employed, targeting a plateau pressure <30 cm H2O. iPEEP should be monitored by performing
an end-expiratory hold maneuver. The iPEEP is equal to total PEEP minus set PEEP (set on
ventilator) (Fig. 11.1). The goal should be to maintain iPEEP <20 cm H2O.
ADDITIONAL CONSIDERATIONS
Hypotension during or post-intubation is common in status asthmaticus because of multiple factors,
including the application of positive pressure throughout the respiratory cycle in patients with preexisting DHI and iPEEP, hypovolemia, and sedation. It should be managed with sedatives and
liberal intravenous fluids (IVF) as well as the aforementioned ventilatory strategies to minimize
DHI. If needed, with close monitoring of SpO2, the patient can be disconnected from the ventilator
circuit to allow adequate exhalation of trapped gas and decrease intrathoracic pressure.
Neuromuscular blockade should be considered in patients with status asthmaticus on mechanical
ventilation who demonstrate considerable patient-ventilator dyssynchrony with unacceptably high
plateau pressures and iPEEP despite adequate sedation and analgesia. Neuromuscular blocking
agents should be given as
P.74
intermittent boluses with neuromuscular (train of four) monitoring. Administration of
neuromuscular blocking agents as continuous infusions should be avoided because of the increased
risk of myopathy associated with concurrent corticosteroid use.

Figure 11.1. Intrinsic positive end-expiratory pressure (PEEP). Ppk, peak pressure; Pplat, plateau
pressure

TABLE 75.E1 n TheophyllineDosinginAdultswithAcuteBronchospasm


DOSING INTRAVENOUS AMINOPHYLLINE*
Loading Dose (over 20 minutes) 5 mg/kg predicted body weight (PBW)
History of theophylline use:
None
Oral theophylline use 03 mg/kg PBW
Maintenance Dose
Patient category:
Nonsmoker 0.6 mg/kg PBW/h
Smoker 0.3 mg PBW/kg/h
Critically ill 0.6 mg PBW/kg/h
Congestive heart failure 0.2 mg PBW/kg/h
Severe pneumonia 0.2 mg PBW/kg/h
*Dosing expressed in aminophylline equivalents (theophylline dose = 0.8 aminophylline dose).
If possible, serum theophylline levels should be obtained before administration, especially if there
is a history of
theophylline use.
Predicted body weight (PBW) for adults can be estimated from formulas in footnotes of Table
17.1 or Table
73.2 or from Appendix Fs Tables of PBW according to height of women and men.
Theophylline levels should be measured 12 to 24 hours after loading and more frequently if
symptoms or signs
of theophylline toxicity are evident. Target level = 8 to 10 g/mL. A 1-mg/kg PBW aminophylline
dose will
increase the serum concentration by approximately 2 g/mL.
From Dellinger RP: Life-threatening asthma. In Parillo JE, Dellinger RP (eds): Critical Care
Medicine:
Principles of Diagnosis and Management in the Adult, 2nd ed. St Louis: Mosby, 2001, p
729.INTRODUCTION Asthma is one of the most common medical conditions encountered
during pregnancy, occurring in 3 to 8 percent of pregnant women [1-5]. Pregnancy may be
associated with changes in the course of asthma, and asthma may affect the outcome of pregnancy.
The management of asthma in pregnancy, including general management issues, the safety data for
specific asthma medications, and recommended pharmacotherapy for acute and chronic asthma in
pregnancy, is reviewed here. The physiology and clinical course of asthma in pregnancy are
discussed separately. (See "Physiology and clinical course of asthma in pregnancy".)
OVERVIEW OF MEDICATIONS IN PREGNANCY Two important considerations arise with
the use of any medication in pregnancy:
Are there potential adverse effects of the medication on the developing fetus?
Does pregnancy alter the metabolism or the bioavailability of the medication?
Potential adverse effects Medications administered during pregnancy have been associated with
an increased risk of several adverse outcomes, which are not independent, including:

Miscarriage
Fetal death
Congenital malformation (especially first trimester exposure)
Reduced fetal growth
Impaired function of developing organs, such as the central nervous system or kidney
Reduced uteroplacental blood flow
Increased risk of preterm delivery
Drug related side effects in the newborn

Information about potential adverse effects must be interpreted with an understanding that the
baseline frequency of complications in pregnancy is relatively high, even in the absence of asthma
or other disorders. In the United States, major congenital anomalies occur in 3 percent of liveborn
infants; miscarriages, in 10 to 15 percent of clinically diagnosed pregnancies; 12 percent of births
are preterm; one in 200 pregnancies end in stillbirth; and mental retardation (IQ <70) is diagnosed
in 1 to 2 percent of children/adults [6-9].
There is a small but significant increase in complications of pregnancy in asthmatic women [10].
The largest study reported to date suggests that asthmatic patients, on average, have a 15 to 20
percent increased risk of perinatal mortality, preeclampsia, preterm delivery, or low birth weight
infants compared to non-asthmatic women, and that patients with more severe asthma have a 30 to
100 percent increased risk (table 1) [10]. This study did not find an increased risk of congenital
malformations in the infants of asthmatic mothers.
Relatively few drugs have been proven harmful in pregnancy and less than 1 percent of congenital
malformations can be attributed to drugs; however, statistical and ethical considerations make it
unlikely that any drug will ever be "proven safe" [11,12]. Although unnecessary use of medication
during pregnancy should be avoided, the risks of untreated disease must be considered in parallel.
Fortunately, a relatively large body of evidence supports the use of several important therapies for
asthma during pregnancy.
Assessing risk of medications The risk associated with use of a specific medication in pregnancy
can be assessed using several sources of information.
Human data Human data exist in the form of case reports, cohort studies, and case-control
studies [12]. Case reports, in which an exposure and an outcome are presented, provide
limited data regarding cause and effect. Cohort studies prospectively evaluate exposed and
non-exposed populations to determine outcome, and case-control studies retrospectively
evaluate affected and non-affected subjects for whether or not they were exposed.
Negative cohort studies are reassuring. However, they rarely include sufficient numbers of
exposed individuals to rule out a small (but important) increase in adverse pregnancy
outcome, particularly when dealing with outcomes such as specific malformations, the most
common of which may only occur in 3 per 1000 births [13].
Positive cohort or case-control studies do not prove causation and generally suggest
hypotheses requiring independent confirmation [12,14,15]. Nonetheless, when effective
alternatives are available, drugs that have been implicated as causing adverse effects in
cohort or case-control studies should be avoided.
Animal data Animal teratology experiments can be useful in evaluating human drug risks,
although animals differ from humans in a number of ways. Animal studies are designed to
maximize the response of the system to potential toxic effects of the test agent by using large
doses [11].
It is believed that a testing scheme using appropriate doses in at least two species, one of
which is a non-rodent, is sufficient to raise suspicion of human developmental risk. There
are, in fact, no known human developmental toxicants that would not have been identified in
this manner [11]. Thus, if an agent is appropriately tested in animals and found not to be a
developmental toxicant, its potential for human developmental toxicity is low [16].
By comparison, positive data in animal studies are not as useful because it is frequently not
possible to know whether species differences, the clinically irrelevant high doses used, or
maternal toxicity was responsible for the adverse effects on the offspring [11].
FDA categories The United States Food and Drug Administration established five

categories to describe a drug's potential for causing adverse effects during pregnancy (table
2) and mandated that newly approved drugs introduced after November 1, 1980 be classified
into one of these categories in the package insert [15]. The categories are based on the
results of animal studies, human data, and consideration of whether the benefit of the drug's
use during pregnancy outweighs the risk.
No asthma or allergy medication labeled to date meets the requirements for category A.
Most category B drugs are labeled as such because of reassuring animal studies without
"adequate and controlled" human data. As an example, budesonide is classified as a category
B drug based on reassuring data from the population-based Swedish Medical Birth Registry
[17]. One may wish to choose class B versus C drugs among equally effective alternatives
due to the reassuring animal studies. Category D provides a strong relative contraindication
to use in pregnancy, and category X drugs should not be used. Over the years, increasing
dissatisfaction has arisen regarding the clinical usefulness of these categories [18], and the
FDA is currently developing a new, more descriptive system of pregnancy labeling [19].
Other considerations A topical medication would appear to be preferable to a systemic one
due to reduced likelihood of fetal penetration. An older medication with a "track record"
may be preferable to a newer one. Finally, absolute and relative efficacy must also be
considered in the choice of a medication for use during pregnancy.
Altered pharmacokinetics The issue of altered pharmacokinetics of medications during
pregnancy is relevant to theophylline and aminophylline. (See 'Methylxanthines' below.)
GENERAL CARE Asthma may improve, worsen, or remain unchanged in severity during
pregnancy. The potential mechanisms involved and clinical implications of these findings are
discussed separately. (See "Physiology and clinical course of asthma in pregnancy".)
The two primary goals of asthma management, ie, prevention of acute episodes and optimization of
ongoing pulmonary function, are unchanged in the setting of pregnancy, and should serve to
maximize both maternal and fetal health [20]. Prevention of acute episodes should prevent
potentially harmful acute hypoxia, hypocapnia, alkalosis, and dehydration. Optimization of chronic
maternal pulmonary function should reduce the potential for chronic hypoxia, maternal symptoms,
as well as the likelihood of acute episodes.
Careful follow-up by clinicians experienced in managing asthma is essential. Asthmatic women
requiring regular medication should be evaluated at least monthly. All pregnant patients should have
ready access to their clinician should their symptoms change or increase. It is also important that
effective communication exists among the clinician managing the asthma, the patient, and the
obstetrician.
The Expert Panel Report of the Working Group on Asthma and Pregnancy stressed the following
four important components of effective therapy [21]:
Objective monitoring of maternal lung function and fetal wellbeing as a guide to therapy
(see "An overview of asthma management", section on 'Monitoring patients with
asthma' and "Peak expiratory flow rate monitoring in asthma" and "Overview of fetal
assessment")
Proper control of environmental and other triggers for asthma (see "Trigger control to
enhance asthma management")
Patient education (see "What do patients need to know about their asthma?")
Pharmacologic therapy
Monitoring lung function Diminished pulmonary function during pregnancy is associated with
adverse perinatal outcomes [22,23]; it is therefore important to monitor pulmonary function in
patients with asthma. Normal pregnancy-related changes in pulmonary function are discussed
separately. (See "Respiratory tract changes during pregnancy".)

Asthmatic symptoms are often greatest at night, leading to nocturnal awakening, or when waking up
in the morning. Functional assessment by the patient during times of worsening symptoms may
provide a more accurate reflection of the patient's condition than spirometric measurements at the
clinician's office.
Although monitoring pulmonary function using spirometry can be useful, measurement of peak
expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV1), using a portable
device offers the advantages of less expense and greater ease of serial measurements at home.
Ideally, patients with asthma should measure their PEFR twice a day: upon awakening and
approximately 12 hours later. (See "Peak expiratory flow rate monitoring in asthma".)
An additional issue for pregnant women with asthma is the difficulty differentiating an exacerbation
of asthma symptoms from the normal sensation of dyspnea experienced during pregnancy. The
presence of cough and wheezing suggests asthma. Objective information can also be obtained by
measurement of the PEFR or FEV1; reductions in either suggest an asthma exacerbation. (See
"Dyspnea during pregnancy" and "Diagnosis of asthma in adolescents and adults", section on
'Pulmonary function testing'.)
Smoking cessation It is critical for the pregnant asthmatic woman to discontinue smoking during
pregnancy [24]. First, smoking may predispose the patient to asthma exacerbations, bronchitis or
sinusitis, and therefore necessitate an increased need for medication [25]. Second, the increased
perinatal morbidity attributed to smoking may be additive to the baseline risk conferred by
uncontrolled maternal asthma [23]. (See "Smoking and pregnancy", section on 'Smoking
cessation'.)
Environmental control Control of environmental triggers is an important component of the
management of asthma during pregnancy. This includes avoiding exposure to allergens and to
nonspecific airway irritants, such as tobacco smoke, dust, and environmental pollutants. Particular
allergens of concern are dander from pets and antigens from household dust mites. (See "Allergen
avoidance in the treatment of asthma and allergic rhinitis" and "Trigger control to enhance asthma
management".)
Patient education The principles of patient education are generally similar for the pregnant and
nonpregnant patient with asthma. Important issues include early recognition of signs and symptoms
of an asthma exacerbation, avoidance of precipitating factors, correct use of medications, and
development of a treatment plan for acute exacerbations.
The primary issues that are specific for pregnancy are education about the interrelationships
between asthma and pregnancy and the safety of asthma medications during pregnancy. The
clinician should clearly explain that it is safer for pregnant women with asthma to take asthma
medications than to have ongoing symptoms or exacerbations of asthma [22,26].
Asthma may add to the stress of normal pregnancy, and the stress of pregnancy may aggravate
asthma [27]. It is important that anxiety regarding asthma and its impact on pregnancy be reduced
by giving women the opportunity to express their concerns and then providing appropriate
information [28]. Women should be reassured that safe and adequate asthma treatment is possible
during pregnancy and that good asthma control can help to minimize the risk of complications.
Educational material for pregnant asthmatic patients has been published [29]. General and
pregnancy-specific patient information is provided separately. (See "What do patients need to know
about their asthma?" and "Patient information: Asthma and pregnancy (Beyond the Basics)".)
SAFETY OF SPECIFIC MEDICATIONS Experience with many of the medications used to treat
asthma suggests minimal or no known adverse effects for their use during pregnancy [13,7,14,17,21,30-34]. Most drugs used in the treatment of asthma fall into categories B or C.
Additional information and links to national databases for reproductive teratology are provided
separately. (See "Principles of teratology".)

Overview Cohort studies are reassuring and show a lack of adverse effects on human pregnancy
outcomes with the following drugs [21]:

Albuterol [14,31]
Metaproterenol [35]
Theophylline [14,30,36]
Cromolyn sodium [30,37]
Beclomethasone [30,32]
Budesonide [17,38]

In contrast, data regarding the use of oral glucocorticoids during pregnancy have not been totally
reassuring. (See 'Oral/Systemic' below.)
For a number of asthma medications, there are minimal or no published human data. These include
drugs with reassuring animal studies (formoterol, salmeterol, ipratropium, nedocromil, zafirlukast,
and montelukast) and those with non-reassuring animal studies (zileuton). Each of the major classes
of medication currently in use for asthma is discussed below.
Inhaled beta-adrenergic agonists The majority of reports provide reassurance regarding the use
of inhaled beta-agonists during pregnancy [14,31,35]. Clinical experience is greater with the older
agents (eg, albuterol) than with the newer ones (eg, formoterol, salmeterol).
Short-acting beta-adrenergic agonists The short-acting, selective beta-2 adrenergic
bronchodilators (SABAs) are used to provide quick relief of asthma symptoms and appear to be
relatively safe during pregnancy.
In animal studies, some of the SABAs have been teratogenic when given in high doses, but there
has been no clear evidence of teratogenicity in humans. In a study of 259 pregnant asthmatic
women, for example, no adverse effects on the fetus were noted with the use of an inhaled SABA
(primarily metaproterenol) when compared with control subjects, even though 180 of the women
used these agents during the first trimester [35]. However, in a case-control study, a small increased
risk of gastroschisis was reported among infants exposed in utero to bronchodilators [39]. An
association with cardiac defects was noted in a cohort study that examined the effect of exposure to
bronchodilator therapy during pregnancy [40]. One problem with assessing the consequences of
bronchodilator use in pregnancy is confounding introduced by indication; SABA use is a marker for
poorly-controlled asthma and more frequent exacerbations, which may independently contribute to
the development of congenital anomalies [26].
Systemic betaadrenergic agonists have also been used as tocolytic agents (ie, as inhibitors of
uterine contraction) in the setting of premature labor. When given for this indication, the major
maternal concern is resultant hyperglycemia. Prenatally exposed neonates have been found to have
tachycardia, hypoglycemia, and tremor; these effects in the neonate, however, have been treatable,
are reversible, and are therefore not considered a contraindication to use. (See "Inhibition of acute
preterm labor", section on 'Beta-adrenergic receptor agonists'.)
There is preliminary evidence that the use of SABAs during pregnancy could have other beneficial
effects for some asthmatic women. In one nested case-control cohort study [41], SABA use during
pregnancy was associated with a significantly reduced risk of gestational hypertension (ie,
hypertension without proteinuria), although the risk of overt preeclampsia (ie, hypertension with
proteinuria) was not affected. Further studies are needed to establish causality, since nonasthmatic
pregnant controls were not included in this observational study and residual confounding could
therefore not be excluded. Inhaled SABAs, however, can reduce diastolic blood pressure in nonpregnant patients, a finding that could provide a plausible biologic mechanism for this effect [42].
These findings are preliminary; clinicians should continue with the goal of minimizing use of
SABAs in both pregnant and non-pregnant patients.
Long-acting beta-adrenergic agents Clinical experience with inhalation of the long-acting,

selective beta-2 adrenergic bronchodilators (LABAs) during pregnancy is less extensive than with
the short-acting bronchodilators (SABAs). Salmeterol is not expected to increase the risk of
congenital anomalies, based on data from animal studies and limited human experience [43].
Animal studies are also reassuring for formoterol, although data from human pregnancies is very
limited [44,45].
Given these findings, continuation of a LABA during pregnancy is reasonable if a LABA has been
needed to achieve asthma control before pregnancy [46,47].
The indications for LABA therapy in asthma, the importance of combining LABA therapy with an
inhaled glucocorticoid, and the controversy regarding the safety of LABA therapy are discussed
separately. (See "Treatment of moderate persistent asthma in adolescents and adults", section on
'Medium-dose inhaled GCs plus a LABA' and "Treatment of severe asthma in adolescents and
adults", section on 'Combination inhaled GC/LABA' and "Beta agonists in asthma: Controversy
regarding chronic use", section on 'Long-acting beta agonists'.)
Epinephrine Concern has been raised that the alphaadrenergic effects of epinephrine might
cause vasoconstriction in the uteroplacental circulation. Although there is no objective evidence that
this is a problem in humans, the Working Group on Pregnancy and Asthma recommended that
epinephrine generally be avoided during pregnancy except in the setting of anaphylaxis [21]. For
the rare patient who requires use of a systemic beta-agonist to treat asthma, subcutaneous
administration of terbutaline is a reasonable choice (table 3).
Glucocorticoids Because of their importance in the treatment of a variety of inflammatory
conditions, systemic glucocorticoids have been used fairly extensively during pregnancy. Similarly,
inhaled glucocorticoids are frequently used for asthma control during pregnancy, although
randomized trials have not been performed.
Oral/Systemic Several potential areas of concern have been raised with the use of systemic
glucocorticoids: congenital malformations (primarily cleft palate), preeclampsia, gestational
diabetes, low birth weight, and neonatal adrenal insufficiency. A few studies exist in which systemic
glucocorticoids were used for the management of asthma during pregnancy [14,30,31,48-50]. Some
showed a slightly increased risk of prematurity and a slightly higher risk of low birth weight (less
than 2500 g) [14,31,49].
Congenital malformations Data from animal studies in several species suggest that high
dose systemic glucocorticoids may lead to cleft palate. Palatal closure is usually complete by
the 12th week of pregnancy, so potential risk would be limited to administration during the
first trimester. Human studies are less concerning but a possible effect cannot be dismissed.
A meta-analysis was performed of (1) cohort studies that evaluated the relationship between
first trimester maternal oral glucocorticoid use and total congenital malformations and (2)
case-control studies evaluating the relationship between first trimester maternal oral
glucocorticoid use and oral clefts (cleft lip with or without cleft palate) [51]. No definite
increased association of systemic glucocorticoids with total malformations was identified
from the six cohort studies (summary odds ratio = 1.45, 95% CI of 0.80, 2.60). However, a
meta-analysis of the four case-control studies revealed an association of oral clefts in infants
of oral glucocorticoid-treated mothers (summary odds ratio = 3.35, 95% CI of 1.97, 5.69).
In a cohort study, the outcomes of 311 pregnancies with systemic glucocorticoid use for
various indications during the first trimester were compared with those of 790 controls
without teratogenic exposure; the rate of major anomalies did not differ significantly
between the groups [52]. No oral cleft abnormalities were noted in the glucocorticoid group.
Preterm birth and low birth weight A large, prospective, cohort study of 2123 pregnant
women with asthma recruited from 16 centers in the United States in the period from
December 1994 to February 2000 found that oral glucocorticoid use was significantly
associated with preterm birth (odds ratio 1.54, 95% CI of 1.02 to 2.33) and low birth weight

(odds ratio 1.80, 95% CI of 1.13 to 2.88) [14]. Increased prematurity and/or lower birth
weights have been noted in other studies as well [31,48,49,51-54]. The authors did not
evaluate the relationship between these effects and the dose or duration of therapy.
Other adverse outcomes Preeclampsia has been attributed to oral glucocorticoid use in
several studies [30,55,56]. Neonatal adrenal insufficiency following maternal administration
of glucocorticoids is distinctly unusual, probably because the nonhalogenated
glucocorticoids do not readily cross the placenta [27]. Gestational diabetes and hypertension
are additional potential maternal complications of systemic glucocorticoid administration
[53].
However, it is difficult to exclude an adverse pregnancy effect due to asthma in studies of patients
with asthma symptoms severe enough to require oral glucocorticoids. In addition, the potential
gestational risks of oral glucocorticoids must be balanced against the risks to the mother or the
infant of inadequately treated disease. In the case of asthma, the risks of severe uncontrolled disease
(which may include maternal or fetal mortality) are generally considered to be the greater risk,
suggesting that oral glucocorticoids should still be used when indicated for the management of
severe gestational asthma [21,34].
Inhaled In contrast to oral/systemic glucocorticoids, the safety data on inhaled glucocorticoids
are reassuring [14,17,32,48,56-65]. The safety of these medicines was best assessed in a registrybased cohort study of 2014 Swedish women who used inhaled budesonide during early pregnancy
[17]. The rate of congenital malformations was not different from that of the general population (3.8
versus 3.5 percent). Additional data from the Swedish Medical Birth Registry reported no clinically
significant effects of inhaled budesonide on fetal mortality, gestational age, or fetal growth [38].
Based largely upon these findings, budesonide is currently the only inhaled glucocorticoid with a
pregnancy category B rating [21].
In addition, a separate study of 13,280 pregnancies in women with asthma confirmed that low to
moderate doses of inhaled glucocorticoids were NOT associated with an increased risk of
congenital malformations. However, the use of high doses (>1000 mcg/day) during the first
trimester was associated with a 63 percent increase in risk of all congenital malformations [62]. The
strength of this observation is limited because the study was underpowered to assess the risk of
specific malformations, such as cleft palate, which has been associated with maternal use of
systemic glucocorticoids. In addition, the authors could not exclude the possibility that greater
asthma severity contributed to the overall increased risk of malformations. Benefit-risk
considerations favor the use of high dose inhaled glucocorticoids over a lower dose when needed
for asthma control to avoid the use of systemic oral glucocorticoids, with the potential risks listed
above. (See 'Oral/Systemic' above.)
Two randomized controlled trials support the efficacy of inhaled glucocorticoids during pregnancy.
One study assessed 84 pregnant women who were managed with or without inhaled
beclomethasone after discharge following an asthma hospitalization during pregnancy [66]. Use of
this medication significantly decreased the rate of readmission for asthma (12 versus 33 percent),
and no adverse events or outcomes were reported. A more recent study compared inhaled
beclomethasone to theophylline in the management of moderate asthma during pregnancy [59].
Although exacerbation rates were similar in the two groups, pulmonary function was better in the
beclomethasone group and fewer patients in the beclomethasone group discontinued therapy due to
side effects.
Anticholinergic agents Anticholinergic agents, such as atropine, glycopyrrolate, and ipratropium,
are not generally used as a primary form of therapy for asthma. However, questions may arise about
their safety during pregnancy.
Fetal tachycardia can occur with the systemic administration of atropine to the mother; however, the
minimal chronotropic effect of inhaled ipratropium in the mother suggests that the inhaled
preparation should have negligible chronotropic effects on the fetus. Gestational animal studies are

also reassuring for ipratropium [27]. Consequently, inhaled ipratropium, the most commonly used
drug in this category, is felt to be safe during pregnancy [21,67].
Methylxanthines Extensive clinical experience suggests that theophylline and its
ethylenediamine complex, aminophylline, do not increase the risk of adverse effects during
pregnancy [13,30,36,68]. However, the clinical use of these medications is limited because of the
potential for altered metabolism during pregnancy and the need for drug level monitoring.
Moreover, inhaled glucocorticoids have been shown to be more effective than theophylline for
persistent asthma in non-pregnant patients and at least as effective as theophylline with fewer side
effects in pregnant patients [21,59]. Thus, theophylline could be considered as an add-on therapy to
inhaled glucocorticoids for pregnant women if needed [21].
Alterations in drug metabolism There are two changes of potential clinical importance in the
bioavailability and metabolism of theophylline during pregnancy. Decreased binding to albumin
results in an increased proportion of free drug in the circulation [69]. The free drug concentration
itself does not change because the decrease in binding means that more free drug is available for
metabolism. However, the total (free plus bound) theophylline concentration falls. As a result, target
plasma levels during pregnancy are 8 to 12 rather than 10 to 15 micrograms/mL. This can be
achieved without change in drug dose due to the relative constancy of the free drug concentration.
(See "Theophylline use in asthma".)
A second change is that the clearance of theophylline appears to decrease during the third trimester,
possibly requiring a reduction in the maintenance dose [70]. With an intravenous
aminophylline infusion during the third trimester, for example, the loading dose of 5 to 6 mg/kg is
unchanged, but the maintenance infusion rate is decreased from 0.9 mg/kg/hr to approximately 0.5
mg/kg/hr; the dose is then adjusted to maintain the desired plasma level of 8 to 12 micrograms/mL.
Like the beta-2 adrenergic agonists, theophylline can also inhibit uterine muscle contraction in
vitro. This effect is presumably mediated by an inhibitory action of increased cyclic AMP (due to
theophylline-induced phosphodiesterase inhibition) on uterine smooth muscle, but has not been
shown to be clinically important.
Effect on the fetus The methylxanthines are transferred across the placenta, leading to
theophylline concentrations in neonatal and cord blood that are similar to those in maternal blood
[71]. Transient tachycardia and irritability have been reported in some neonates of mothers
receiving methylxanthines.
Cromoglycates Animal data and limited data in human pregnancies (n = 318) have not
demonstrated an increase in fetal malformations or other adverse effects with cromolyn
sodium [30,67]. The one study that reported an increase in musculoskeletal abnormalities with
maternal use of chromones had a very small number of exposures (n = 5), limiting the strength of
the observation [7]. Human data are not available for nedocromil, although preclinical animal
studies suggest that this drug does not increase the risk of adverse effects in pregnancy [21]. (See
"The use of chromones (cromoglycates) in the treatment of asthma".)
The availability of the cromoglycates, cromolyn sodium, and nedocromil, is limited and varies from
one country to another. (See "The use of chromones (cromoglycates) in the treatment of asthma",
section on 'Limitations on availability'.)
Leukotriene modifiers Zafirlukast and montelukast (leukotriene receptor antagonists) and
zileuton (a 5lipoxygenase inhibitor) are agents that affect leukotriene synthesis or action. (See
"Agents affecting the 5-lipoxygenase pathway in the treatment of asthma".)
Data on the use of these agents in pregnancy are limited, but accumulating evidence, particularly
about montelukast, is reassuring.
The first prospective, controlled study of the use of leukotriene receptor antagonists in
pregnancy followed 96 women taking these medications, 122 women taking SABAs only,

and 346 women without asthma. No increase in major birth defects or adverse outcomes was
detected in the offspring of patients receiving these medications [72]. A subsequent study
with similar design described 180 montelukast-exposed pregnancies compared to 180
disease matched controls and 180 pregnancies in non-asthmatic women. In this study,
montelukast did not appear to increase the baseline rate of major malformations, although
lower birth weights were seen in both asthmatic groups [73]. Larger studies are needed to
detect small increases in adverse pregnancy outcomes or rare birth defects.
Data from the Merck Pregnancy Registry that have not been published describe 401
prospective reports of mothers exposed to montelukast during pregnancy, in which 203
reports were complete and reported pregnancy outcomes. There were 250 live births (three
sets of twins), four miscarriages, and two elective abortions. Congenital limb defects have
rarely been reported in children whose mothers were exposed to montelukast during
pregnancy, but a causal association has not been established. The overall rates of congenital
malformations, preterm births, and small-for-dates infants in the Merck prospective registry
were 2.8, 11, and 5 percent, respectively. These results are consistent with those expected in
the general population.
No teratogenicity was observed with montelukast given to rats or rabbits at doses greater
than 300 times the maximum human daily oral dose on an mg/m2 basis [74].
Animal data on zafirlukast have shown no teratogenicity at oral doses up to 160 times the
maximum human daily oral dose on a mg/m2 basis [75].
There are currently no adequate and wellcontrolled studies of zileuton in pregnant women,
and animal studies have not been reassuring [76].
Thus, until further information is available, we suggest use of montelukast in preference to the other
leukotriene modifiers, and would reserve this agent for add-on therapy to inhaled glucocorticoids,
especially in patients who had a good response to this medication prior to pregnancy [21].
Immunotherapy for allergic asthma The initiation of allergen immunotherapy is not
recommended during pregnancy based upon risk-benefit considerations [29]. However, aside from
the risk of systemic reactions, allergy immunotherapy appears to confer minimal additional risk
during pregnancy. Thus, allergen immunotherapy can be continued during pregnancy in patients
already receiving it who appear to be deriving benefit, who are not prone to systemic reactions, and
who are receiving a maintenance concentration or at least a substantial dosage. Immunotherapy
during pregnancy is discussed in more detail elsewhere. (See "Recognition and management of
allergic disease during pregnancy", section on 'Allergen immunotherapy'.)
OVERVIEW OF ASTHMA MANAGEMENT IN PREGNANCY The general principles of
pharmacologic therapy for asthma during pregnancy are similar to those in nonpregnant patients
and involve a step-wise approach, as recommended by the "The National Asthma Education and
Prevention Program: Expert Panel Report 3 (figure 1 and table 4 and table 5) [77]. The details of
this approach are discussed separately. (See "An overview of asthma management".)
The Working Group on Asthma and Pregnancy of the National Asthma Education Program
reviewed the available data on asthma medications and made recommendations regarding
medication preferences in the management of chronic asthma, acute asthma, respiratory infections,
and peripartum care during pregnancy [21,77,78].
Chronic asthma The NAEPP 2007 recommendations for the management of chronic asthma
during pregnancy are shown in the table (table 6). The following points are emphasized:
Either medium dose inhaled glucocorticoids or combination low dose inhaled
glucocorticoids plus a long acting beta agonist (LABA) are recommended for the initial
management of moderate persistent asthma; our preference is for the former due to the

greater experience with inhaled glucocorticoids than with LABAs during pregnancy.
Albuterol is recommended as the short-acting beta agonist of choice.
Because there are more published gestational human data for budesonide [17,79], it is the
preferred inhaled glucocorticoid for use during pregnancy. However, other inhaled
glucocorticoids could be continued if the patient was well-controlled on one of these
medications prior to pregnancy.
Salmeterol is recommended as the inhaled long-acting beta agonist of choice in the United
States due to the longer duration of clinical experience with this agent compared with
formoterol.
Montelukast or zafirlukast could be considered as alternative but NOT preferred therapy for
mild persistent asthma or as add-on therapy to inhaled glucocorticoids, especially for
patients who have shown a uniquely favorable response prior to pregnancy.

Acute exacerbations The recommended pharmacotherapy of acute asthma during pregnancy


does not differ substantially from the management in non-pregnant patients (table 3) [80]. Intensive
monitoring of both mother and fetus is essential. (See "Overview of fetal assessment".)
Supportive care Supplemental oxygen (initially 3 to 4 L/min by nasal cannula) should be
administered, adjusting the fraction of inspired oxygen (FiO2) to maintain an arterial oxygen
tension (PaO2) of at least 70 mmHg and/or oxygen saturation by pulse oximetry of 95 percent or
greater [81]. Intravenous fluids (containing glucose if the patient is not hyperglycemic) are
administered, if needed to ensure adequate hydration. Pregnant patients with acute asthma should
rest in a seated, rather than supine, position.
Continuous fetal heart rate monitoring as well as maternal monitoring is essential, and the fetal
heart rate tracing should be evaluated by a clinician experienced in fetal heart rate assessment.
Interpretation of arterial blood gases The changes in blood gases that occur secondary to acute
asthma during pregnancy are superimposed on the "normal" respiratory alkalosis of pregnancy.
Thus, an arterial carbon dioxide tension (PaCO2) >35 mmHg or an arterial oxygen tension (PaO2)
<70 mmHg associated with acute asthma represent more severe compromise during pregnancy than
in the non-gravid state. (See "Physiology and clinical course of asthma in pregnancy".)
Medications The recommended agents for management of acute asthma exacerbations in
pregnant patients include inhaled beta agonists, inhaled anticholinergic agents, oral or intravenous
glucocorticoids, and, if appropriate, intravenous magnesium sulfate (table 3). (See "Treatment of
acute exacerbations of asthma in adults".) Additional points regarding pharmacotherapy include the
following:
Dosages of systemic glucocorticoids for acute asthma exacerbations in pregnancy are not
different than those recommended for non-pregnant patients [82]. (See "Treatment of acute
exacerbations of asthma in adults", section on 'Systemic glucocorticoids'.)
Intravenous aminophylline/theophylline is NOT generally recommended for use in the
emergency management of acute gestational asthma because it has been demonstrated that
aminophylline/theophylline provides no additional benefit to optimal inhaled beta agonist
and intravenous glucocorticoid therapy [66,81]. In addition, when used in combination with
intensive inhaled beta-agonist therapy, intravenous aminophylline causes increased adverse
side effects [81].
Intravenous magnesium sulfate may be beneficial in acute severe asthma as an adjunct to
inhaled beta agonists and intravenous glucocorticoids, especially in patients with coexistent
hypertension or preterm uterine contractions [82]. Magnesium sulfate is among the most
extensively studied medications in pregnancy. It is routinely given to prevent eclamptic
seizures in the mother and appears to have neuroprotective effects for the neonate if
administered prior to preterm birth. (See "Treatment of acute exacerbations of asthma in

adults", section on 'Magnesium sulfate' and "Neuroprotective effects of in utero exposure to


magnesium sulfate".)
A more detailed discussion of the treatment of acute exacerbations of asthma, including status
asthmaticus, is provided separately. (See "Treatment of acute exacerbations of asthma in adults".)
Respiratory infections Most respiratory infections that trigger an exacerbation of asthma are viral
rather than bacterial and do not require antibiotic therapy [77]. The treatment of respiratory
infections during pregnancy is discussed separately. (See "Treatment of respiratory infections in
pregnant women".)
Peripartum care A few additional issues are relevant to the peripartum management of the
asthmatic patient [81]:
Oxytocin is the drug of choice for induction of labor and control of postpartum hemorrhage
[83]. (See "Management of postpartum hemorrhage at vaginal delivery", section on
'Uterotonic drugs' and "Management of postpartum hemorrhage at cesarean delivery",
section on 'Initial management' and "Principles of labor induction", section on 'Guidelines'.)
Analogs of prostaglandin F2alpha can cause bronchoconstriction [84,85] and should not be
used for termination of pregnancy, cervical ripening, induction of labor, or control of uterine
hemorrhage. Prostaglandin E2 (in gel or suppository form) and prostaglandin E1
(misoprostol) have not been reported to cause bronchoconstriction and are safer analogs if
prostaglandin treatment is required [86].
For peripartum pain control, morphine and meperidine should be avoided, if possible, since
they can induce histamine release, however, evidence of acute bronchoconstriction caused
by these agents is lacking. Butorphanol or fentanyl may be appropriate alternatives.
Epidural anesthesia is preferred for the asthmatic patient who opts for pain control during
labor because it reduces oxygen consumption and minute ventilation in the first and second
stage of labor and usually can provide adequate anesthesia if cesarean delivery becomes
necessary.
If general anesthesia is required, ketamine and halogenated anesthetics are preferred,
because they may have a bronchodilatory effect.
Use of ergot derivatives for postpartum bleeding or headache should be avoided because of
their potential to cause bronchoconstriction.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials,
The Basics and Beyond the Basics. The Basics patient education pieces are written in plain
language, at the 5th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who want a general
overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade
reading level and are best for patients who want in-depth information and are comfortable with
some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient information: Asthma and pregnancy (The Basics)")
Beyond the Basics topics (see "Patient information: Asthma treatment in adolescents and
adults (Beyond the Basics)" and "Patient information: Asthma and pregnancy (Beyond the
Basics)" and "Patient information: Trigger avoidance in asthma (Beyond the Basics)" and
"Patient information: How to use a peak flow meter (Beyond the Basics)" and "Patient
information: Asthma inhaler techniques in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS

Asthma may improve, worsen, or remain unchanged in severity during pregnancy. The
potential mechanisms involved and clinical implications of these findings are discussed
separately. (See "Physiology and clinical course of asthma in pregnancy".)
The two primary goals of asthma therapy during pregnancy are the prevention of acute
exacerbations and optimization of ongoing pulmonary function. (See 'General care' above.)
The four important components of effective asthma therapy during pregnancy are (see
'General care' above):
Objective monitoring of maternal lung function and fetal wellbeing as a guide to therapy
(see "An overview of asthma management", section on 'Monitoring patients with
asthma' and "Overview of fetal assessment")
Proper control of environmental and other triggers for asthma (eg, cigarette smoking, animal
allergen exposure) (see "Trigger control to enhance asthma management")
Patient education (see "What do patients need to know about their asthma?")
Pharmacologic therapy
Studies are reassuring regarding a lack of adverse effects on human pregnancy outcomes
with albuterol, metaproterenol, theophylline, beclomethasone, and budesonide. Reassuring
animal studies have been reported with salmeterol, formoterol, ipratropium, nedocromil,
zafirlukast, and montelukast, but published experience in human pregnancy with these
agents is limited. (See 'Overview' above.)
The general principles of pharmacologic therapy for asthma during pregnancy are similar to
those in nonpregnant patients and involve a step-wise approach, as recommended by the
"The National Asthma Education and Prevention Program (NAEPP): Expert Panel Report 3
(figure 1 and table 4 and table 5 and table 6). (See 'Overview of asthma management in
pregnancy' above and "An overview of asthma management".)
A few medication preferences have been identified for asthma management during
pregnancy based on greater experience in treating patients with these medications (see
'Chronic asthma' above):
For relief of acute asthma symptoms, we suggest using the short-acting beta agonist (SABA)
albuterol, rather than other SABAs (Grade 2C).
For patients who require a long-term controller for asthma, we suggest using budesonide as
the preferred inhaled glucocorticoid (Grade 2C). However, other inhaled glucocorticoids can
be continued if the patient was well-controlled on one of these medications prior to
pregnancy or if a higher dose of inhaled glucocorticoid is needed than is available with
budesonide.
For the initial management of moderate persistent asthma, national guidelines suggest either
medium dose inhaled glucocorticoids or the combination of low dose inhaled
glucocorticoids plus a long acting beta agonist (LABA); we suggest using medium dose
inhaled glucocorticoids due to the greater experience with inhaled glucocorticoids than with
LABAs during pregnancy (Grade 2C). (See 'Chronic asthma' above and "Treatment of
moderate persistent asthma in adolescents and adults", section on 'Preferred options'.)
The management of acute asthma exacerbations during pregnancy does not differ
substantially from that of non-pregnant patients and includes inhaled short-acting beta
agonist albuterol, inhaled anticholinergic agents, oral or intravenous glucocorticoids, and, if
appropriate, intravenous magnesium sulfate (table 3). Intensive monitoring of both mother
and fetus is essential. (See 'Acute exacerbations' above.)
Potential areas of concern have been raised with the use of systemic glucocorticoids,
including slightly increased risks of congenital malformations (primarily cleft palate),
preeclampsia, low birth weight, and neonatal adrenal insufficiency. However, these potential
risks of systemic glucocorticoids are small compared with the substantial risk to the mother

and fetus of severe, uncontrolled asthma. Dosages of glucocorticoids for treatment of acute
asthma exacerbations in pregnancy are not different than those for non-pregnant patients.
(See 'Oral/Systemic' above.)
For the rare patient who requires use of a systemic beta-agonist to treat asthma, we suggest
subcutaneous administration of terbutaline rather than epinephrine (table 3) (Grade 2C). This
is based on a concern about potential uterine artery vasoconstriction with systemic
administration of epinephrine (table 3). (See 'Epinephrine' above.)
We recommend not initiating allergen immunotherapy during pregnancy (Grade 1B).
However, allergen immunotherapy can be continued during pregnancy in patients already
receiving it who appear to be deriving benefit, who are not prone to systemic reactions, and
who are receiving a maintenance concentration or at least a substantial dosage. (See
'Immunotherapy for allergic asthma' above.)
For pharmacologic induction of labor and control of postpartum hemorrhage in patients with
asthma, oxytocin appears to be safe in pregnancy. (See 'Peripartum care' above and
"Management of postpartum hemorrhage at vaginal delivery", section on 'Uterotonic
drugs' and "Principles of labor induction", section on 'Oxytocin'.)
For patients with asthma who require prostaglandin treatment for termination of pregnancy,
cervical ripening, induction of labor, or control of uterine hemorrhage, we recommend using
prostaglandin E1 or E2, rather than analogs of prostaglandin F2alpha (Grade 1B). This
recommendation is based on the risk of bronchoconstriction associated with the latter agent.
(See 'Peripartum care' above.)