Part 10.5: Near-Fatal Asthma
Asthma accounts for Ͼ2 million emergency department Primary Therapy
visits and 5000 to 6000 deaths annually in the United
States, many occurring in the prehospital setting.1 Severe
Provide oxygen to all patients with severe asthma, even those
asthma accounts for approximately 2% to 20% of admissions
with normal oxygenation. Titrate to maintain SaO Ͼ
to intensive care units, with up to one third of these patients
noted above, successful treatment with ␤-agonists may ini-
requiring intubation and mechanical ventilation.2 This section
tially cause a decrease in oxygen saturation because the
focuses on the evaluation and treatment of patients with
resultant bronchodilation may initially increase the
Pathophysiology Inhaled ␤2-Agonists
The pathophysiology of asthma consists of 3 key
Albuterol (or salbutamol) provides rapid, dose-dependent
bronchodilation with minimal side effects. Because the ad-
ministered dose depends on the patient’s lung volume and
inspiratory flow rates, the same dose can be used in most
patients regardless of age or size. Although 6 adult studies5
and 1 pediatric study6 showed no difference in the effects of
Complications of severe asthma, such as tension pneumo-
continuous versus intermittent administration of nebulized
thorax, lobar atelectasis, pneumonia, and pulmonary edema,
albuterol, continuous administration was more effective in the
can contribute to fatalities. Cardiac causes of death are less
subset of patients with severe exacerbations of asthma,7,8 and
it was more cost-effective in a pediatric trial.6 A Cochranemeta-analysis showed no overall difference between the
Clinical Aspects of Severe Asthma
effects of albuterol delivered by metered dose inhaler (MDI)-
Wheezing is a common physical finding, but severity does
spacer or nebulizer,9 but MDI-spacer administration can be
not correlate with the degree of airway obstruction. The
difficult in patients in severe distress. The typical dose of
absence of wheezing may indicate critical airway obstruction,
albuterol by nebulizer is 2.5 or 5 mg every 15 to 20 minutes
whereas increased wheezing may indicate a positive response
intermittently or continuous nebulization in a dose of 10 to 15
Oxygen saturation (SaO2) levels may not reflect progressive
Levalbuterol is the R-isomer of albuterol. It has recently
alveolar hypoventilation, particularly if O2 is being adminis-
become available in the United States for treatment of acute
tered. Note that the SaO2 may initially fall during therapy
asthma. Some studies have shown equivalent or slight im-
because ␤-agonists produce both bronchodilation and vaso-
provement in bronchodilation when compared with albuterol
dilation and may initially increase intrapulmonary shunting.
in the emergency department.10 Further studies are needed
Other causes of wheezing are pulmonary edema, chronic
before a definitive recommendation can be made.
obstructive pulmonary disease (COPD), pneumonia, anaphy-laxis,3 foreign bodies, pulmonary embolism, bronchiectasis,
Systemic corticosteroids are the only proven treatment for theinflammatory component of asthma, but the onset of their
anti-inflammatory effects is 6 to 12 hours after administra-
Patients with severe life-threatening asthma require urgent
tion. A comprehensive search of the literature by the Coch-
and aggressive treatment with simultaneous administration of
rane approach (including pediatric and adult patients) deter-
oxygen, bronchodilators, and steroids. Healthcare providers
mined that the early use of systemic steroids reduced rates of
must monitor these patients closely for deterioration. Al-
admission to the hospital.11 Thus, providers should administer
though the pathophysiology of life-threatening asthma con-
steroids as early as possible to all asthma patients but should
sists of bronchoconstriction, inflammation, and mucous im-
not expect effects for several hours. Although there is no
paction, only bronchoconstriction and inflammation are
difference in clinical effects between oral and intravenous
amenable to drug treatment. If the patient does not respond to
(IV) formulations of corticosteroids,12 the IV route is prefer-
therapy, consultation or transfer to a pulmonologist or inten-
able because patients with near-fatal asthma may vomit or be
unable to swallow. A typical initial adult dose of methylpred-nisolone is 125 mg (dose range: 40 to 250 mg).
Incorporation or substitution of inhaled steroids into this
scheme remains controversial. A Cochrane meta-analysis of 7
randomized trials (4 adult and 3 pediatric) of inhaled corti-
This special supplement to Circulation is freely available at
costeroids concluded that steroids significantly reduced the
likelihood of admission to the hospital, particularly in patients
who were not receiving concomitant systemic steroids. But
IV-139 IV-140 Circulation December 13, 2005
the meta-analysis concluded that there is insufficient evi-
dence that inhaled corticosteroids alone are as effective as
Heliox is a mixture of helium and oxygen (usually a 70:30
helium to oxygen ratio mix) that is less viscous than ambientair. Heliox has been shown to improve the delivery and
deposition of nebulized albuterol.26 Although recent meta-analysis of 4 clinical trials did not support the use of heliox in
the initial treatment of patients with acute asthma,27 it may be
Ipratropium bromide is an anticholinergic bronchodilator that
useful for asthma that is refractory to conventional therapy.28
is pharmacologically related to atropine. It can produce a
The heliox mixture requires at least 70% helium for effect, so
clinically modest improvement in lung function compared
if the patient requires Ͼ30% oxygen, the heliox mixture
with albuterol alone.14,15 The nebulizer dose is 0.5 mg. It has
a slow onset of action (approximately 20 minutes), with peakeffectiveness at 60 to 90 minutes and no systemic side effects. Methylxanthines
It is typically given only once because of its prolonged onset
Although previously a mainstay in the treatment of acute
of action, but some studies have shown clinical improvement
asthma, methylxanthines are infrequently used because of
only with repeated doses.16 Given the few side effects,
erratic pharmacokinetics and known side effects.
ipratropium should be considered an adjunct to albuterol. Tiotropium is a new, longer-acting anticholinergic that is
Leukotriene Antagonists Leukotriene antagonists improve lung function and decrease
currently undergoing clinical testing for use in acute
the need for short-acting ␤-agonists during long-term asthma
therapy, but their effectiveness during acute exacerbations of
asthma is unproven. One study showed improvement in lung
IV magnesium sulfate can modestly improve pulmonary
function with the addition of IV montelukast to standard
function in patients with asthma when combined with nebu-
therapy,29 but further research is needed.
lized ␤-adrenergic agents and corticosteroids.18 Magnesium
causes bronchial smooth muscle relaxation independent of
Case reports in adults30 and children31 suggest a benefit of
the serum magnesium level, with only minor side effects
inhalation anesthetics for patients with status asthmaticus
(flushing, lightheadedness). A Cochrane meta-analysis of 7
unresponsive to maximal conventional therapy. These anes-
studies concluded that IV magnesium sulfate improves pul-
thetic agents may work directly as bronchodilators and may
monary function and reduces hospital admissions, particu-
have indirect effects by enhancing patient-ventilator syn-
larly for patients with the most severe exacerbations of
chrony and reducing oxygen demand and carbon dioxide
asthma.19 The typical adult dose is 1.2 to 2 g IV given over 20
production. This therapy, however, requires an ICU setting,
minutes. When given with a ␤2-agonist, nebulized magne-
and there have been no randomized studies to evaluate its
sium sulfate also improved pulmonary function during acute
asthma but did not reduce rate of hospitalization.20
Parenteral Epinephrine or Terbutaline Assisted Ventilation
Epinephrine and terbutaline are adrenergic agents that can be
Noninvasive Positive-Pressure Ventilation
given subcutaneously to patients with acute severe asthma.
Noninvasive positive-pressure ventilation (NIPPV) may offer
The dose of subcutaneous epinephrine (concentration of
short-term support to patients with acute respiratory failure
1:1000) is 0.01 mg/kg divided into 3 doses of approximately
and may delay or eliminate the need for endotracheal intu-
0.3 mg given at 20-minute intervals. The nonselective adren-
bation.32,33 This therapy requires an alert patient with ade-
ergic properties of epinephrine may cause an increase in heart
quate spontaneous respiratory effort. Bi-level positive airway
rate, myocardial irritability, and increased oxygen demand.
pressure (BiPAP), the most common way of delivering
But its use (even in patients Ͼ35 years of age) is well-
NIPPV, allows for separate control of inspiratory and expi-
tolerated.21 Terbutaline is given in a dose of 0.25 mg
subcutaneously and can be repeated in 30 to 60 minutes. These drugs are more commonly administered to childrenwith acute asthma. Although most studies have shown them
Endotracheal Intubation With
to be equally efficacious,22 one study concluded that terbutal-
Endotracheal intubation does not solve the problem of smallairway constriction in patients with severe asthma. In addi-
tion, intubation and positive-pressure ventilation can trigger
Ketamine is a parenteral dissociative anesthetic that has
further bronchoconstriction and complications such as breath
bronchodilatory properties. Ketamine may also have indirect
stacking (auto-PEEP [positive end-expiratory pressure]) and
effects in patients with asthma through its sedative properties.
barotrauma. Although endotracheal intubation introduces
One case series24 suggested substantial effectiveness, but the
risks, elective intubation should be performed if the asthmatic
single randomized trial published to date25 showed no benefit
patient deteriorates despite aggressive management.
of ketamine when compared with standard care. Ketamine
Rapid sequence intubation is the technique of choice. The
will stimulate copious bronchial secretions.
provider should use the largest endotracheal tube available
Part 10.5: Near-Fatal Asthma IV-141
(usually 8 or 9 mm) to decrease airway resistance. Immedi-
of experienced providers in an intensive care setting. Some
ately after intubation, confirm endotracheal tube placement
tertiary centers can offer experimental therapies as a last resort,
by clinical examination and a device (eg, exhaled CO2
and transfer should be considered for patients with near-fatal
detector) and obtain a chest radiograph.
asthma that is refractory to aggressive medical management. Troubleshooting After Intubation References
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CURRICULUM VITAE DATE OF BIRTH : ADDRESS : TELEPHONE/FAX : 01822 855471 (Home) [email protected] EDUCATION : Secondary Education: The Kings School, Macclesfield, Cheshire. MEDICAL EDUCATION : Charing Cross Hospital Medical School, London. Elective period in Radiotherapy at Centre Leon Berard, Lyon, France QUALIFICATIONS : Certificat de conn
Father Murray Watson – St. Peter’s Seminary, London, Ontario Ask an average Catholic what the word “Pentecost” conjures up in their minds, and you’re bound to hear a lot about tongues of fire and speaking in tongues. You might hear something about the gifts of the Holy Spirit, the sacrament of Confirmation or “the birthday of the Church”. Some might even mention the fiery red vestm