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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 Oxygen
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, Corticosteroids
Systemic corticosteroids are the only proven treatment for theinflammatory component of asthma, but the onset of their Initial Stabilization
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 (Circulation. 2005;112:IV-139-IV-142.)
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 http://www.circulationaha.org
likelihood of admission to the hospital, particularly in patients DOI: 10.1161/CIRCULATIONAHA.105.166567
who were not receiving concomitant systemic steroids. But IV-139
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the meta-analysis concluded that there is insufficient evi- Heliox
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 Adjunctive Therapies
deposition of nebulized albuterol.26 Although recent meta-analysis of 4 clinical trials did not support the use of heliox in Anticholinergics
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 Magnesium Sulfate
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 Inhaled Anesthetics
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- Mechanical Ventilation
Endotracheal intubation does not solve the problem of smallairway constriction in patients with severe asthma. In addi- Ketamine
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
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(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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