ISSN: 1524-4539 Copyright ? 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/CIRCULATIONAHA.105.166567 2005;112;139-142; originally published online Nov 28, 2005; Circulation Part 10.5: Near-Fatal Asthma http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-139 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/static/html/reprints.html Reprints: Information about reprints can be found online at journalpermissions@lww.com Street, Baltimore, MD 21202-2436. Phone 410-5280-4050. Fax: 410-528-8550. Email: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, 351 West Camden http://circ.ahajournals.org/subsriptions/ Subscriptions: Information about subscribing to Circulation is online at by on February 21, 2006 circ.ahajournals.orgDownloaded from Part 10.5: Near-Fatal Asthma A sthma accounts for H110222 million emergency department visits and 5000 to 6000 deaths annually in the United States, many occurring in the prehospital setting. 1 Severe asthma accounts for approximately 2% to 20% of admissions to intensive care units, with up to one third of these patients requiring intubation and mechanical ventilation. 2 This section focuses on the evaluation and treatment of patients with near-fatal asthma. Pathophysiology The pathophysiology of asthma consists of 3 key abnormalities: ● Bronchoconstriction ● Airway inflammation ● Mucous impaction Complications of severe asthma, such as tension pneumo- thorax, lobar atelectasis, pneumonia, and pulmonary edema, can contribute to fatalities. Cardiac causes of death are less common. Clinical Aspects of Severe Asthma Wheezing is a common physical finding, but severity does not correlate with the degree of airway obstruction. The absence of wheezing may indicate critical airway obstruction, whereas increased wheezing may indicate a positive response to bronchodilator therapy. Oxygen saturation (SaO 2 ) levels may not reflect progressive alveolar hypoventilation, particularly if O 2 is being adminis- tered. Note that the SaO 2 may initially fall during therapy because H9252-agonists produce both bronchodilation and vaso- dilation and may initially increase intrapulmonary shunting. Other causes of wheezing are pulmonary edema, chronic obstructive pulmonary disease (COPD), pneumonia, anaphy- laxis, 3 foreign bodies, pulmonary embolism, bronchiectasis, and subglottic mass. 4 Initial Stabilization Patients with severe life-threatening asthma require urgent and aggressive treatment with simultaneous administration of oxygen, bronchodilators, and steroids. Healthcare providers must monitor these patients closely for deterioration. Al- though the pathophysiology of life-threatening asthma con- sists of bronchoconstriction, inflammation, and mucous im- paction, only bronchoconstriction and inflammation are amenable to drug treatment. If the patient does not respond to therapy, consultation or transfer to a pulmonologist or inten- sivist is appropriate. Primary Therapy Oxygen Provide oxygen to all patients with severe asthma, even those with normal oxygenation. Titrate to maintain SaO 2 H1102292%. As noted above, successful treatment with H9252-agonists may ini- tially cause a decrease in oxygen saturation because the resultant bronchodilation may initially increase the ventilation-perfusion mismatch. Inhaled H9252 2 -Agonists 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 studies 5 and 1 pediatric study 6 showed no difference in the effects of continuous versus intermittent administration of nebulized albuterol, continuous administration was more effective in the subset of patients with severe exacerbations of asthma, 7,8 and it was more cost-effective in a pediatric trial. 6 A Cochrane meta-analysis showed no overall difference between the effects of albuterol delivered by metered dose inhaler (MDI)- spacer or nebulizer, 9 but MDI-spacer administration can be difficult in patients in severe distress. The typical dose of albuterol by nebulizer is 2.5 or 5 mg every 15 to 20 minutes intermittently or continuous nebulization in a dose of 10 to 15 mg/h. Levalbuterol is the R-isomer of albuterol. It has recently become available in the United States for treatment of acute asthma. Some studies have shown equivalent or slight im- provement in bronchodilation when compared with albuterol in the emergency department. 10 Further studies are needed before a definitive recommendation can be made. Corticosteroids Systemic corticosteroids are the only proven treatment for the inflammatory component of asthma, but the onset of their anti-inflammatory effects is 6 to 12 hours after administra- tion. A comprehensive search of the literature by the Coch- rane approach (including pediatric and adult patients) deter- mined that the early use of systemic steroids reduced rates of admission to the hospital. 11 Thus, providers should administer steroids as early as possible to all asthma patients but should not expect effects for several hours. Although there is no difference in clinical effects between oral and intravenous (IV) formulations of corticosteroids, 12 the IV route is prefer- 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- costeroids concluded that steroids significantly reduced the likelihood of admission to the hospital, particularly in patients who were not receiving concomitant systemic steroids. But (Circulation. 2005;112:IV-139-IV-142.) ? 2005 American Heart Association. This special supplement to Circulation is freely available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.105.166567 IV-139 the meta-analysis concluded that there is insufficient evi- dence that inhaled corticosteroids alone are as effective as systemic steroids. 13 Adjunctive Therapies Anticholinergics Ipratropium bromide is an anticholinergic bronchodilator that is pharmacologically related to atropine. It can produce a clinically modest improvement in lung function compared with albuterol alone. 14,15 The nebulizer dose is 0.5 mg. It has a slow onset of action (approximately 20 minutes), with peak effectiveness at 60 to 90 minutes and no systemic side effects. It is typically given only once because of its prolonged onset of action, but some studies have shown clinical improvement only with repeated doses. 16 Given the few side effects, ipratropium should be considered an adjunct to albuterol. Tiotropium is a new, longer-acting anticholinergic that is currently undergoing clinical testing for use in acute asthma. 17 Magnesium Sulfate IV magnesium sulfate can modestly improve pulmonary function in patients with asthma when combined with nebu- lized H9252-adrenergic agents and corticosteroids. 18 Magnesium causes bronchial smooth muscle relaxation independent of the serum magnesium level, with only minor side effects (flushing, lightheadedness). A Cochrane meta-analysis of 7 studies concluded that IV magnesium sulfate improves pul- monary function and reduces hospital admissions, particu- larly for patients with the most severe exacerbations of asthma. 19 The typical adult dose is 1.2 to2gIVgiven over 20 minutes. When given with a H9252 2 -agonist, nebulized magne- sium sulfate also improved pulmonary function during acute asthma but did not reduce rate of hospitalization. 20 Parenteral Epinephrine or Terbutaline Epinephrine and terbutaline are adrenergic agents that can be given subcutaneously to patients with acute severe asthma. The dose of subcutaneous epinephrine (concentration of 1:1000) is 0.01 mg/kg divided into 3 doses of approximately 0.3 mg given at 20-minute intervals. The nonselective adren- ergic properties of epinephrine may cause an increase in heart rate, myocardial irritability, and increased oxygen demand. But its use (even in patients H1102235 years of age) is well- 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 children with acute asthma. Although most studies have shown them to be equally efficacious, 22 one study concluded that terbutal- ine was superior. 23 Ketamine Ketamine is a parenteral dissociative anesthetic that has bronchodilatory properties. Ketamine may also have indirect effects in patients with asthma through its sedative properties. One case series 24 suggested substantial effectiveness, but the single randomized trial published to date 25 showed no benefit of ketamine when compared with standard care. Ketamine will stimulate copious bronchial secretions. Heliox Heliox is a mixture of helium and oxygen (usually a 70:30 helium to oxygen ratio mix) that is less viscous than ambient air. 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 useful for asthma that is refractory to conventional therapy. 28 The heliox mixture requires at least 70% helium for effect, so if the patient requires H1102230% oxygen, the heliox mixture cannot be used. Methylxanthines Although previously a mainstay in the treatment of acute asthma, methylxanthines are infrequently used because of erratic pharmacokinetics and known side effects. Leukotriene Antagonists Leukotriene antagonists improve lung function and decrease the need for short-acting H9252-agonists during long-term asthma therapy, but their effectiveness during acute exacerbations of asthma is unproven. One study showed improvement in lung function with the addition of IV montelukast to standard therapy, 29 but further research is needed. Inhaled Anesthetics Case reports in adults 30 and children 31 suggest a benefit of inhalation anesthetics for patients with status asthmaticus unresponsive to maximal conventional therapy. These anes- thetic agents may work directly as bronchodilators and may have indirect effects by enhancing patient-ventilator syn- chrony and reducing oxygen demand and carbon dioxide production. This therapy, however, requires an ICU setting, and there have been no randomized studies to evaluate its effectiveness. Assisted Ventilation Noninvasive Positive-Pressure Ventilation Noninvasive positive-pressure ventilation (NIPPV) may offer short-term support to patients with acute respiratory failure and may delay or eliminate the need for endotracheal intu- bation. 32,33 This therapy requires an alert patient with ade- quate spontaneous respiratory effort. Bi-level positive airway pressure (BiPAP), the most common way of delivering NIPPV, allows for separate control of inspiratory and expi- ratory pressures. Endotracheal Intubation With Mechanical Ventilation Endotracheal intubation does not solve the problem of small airway constriction in patients with severe asthma. In addi- tion, intubation and positive-pressure ventilation can trigger further bronchoconstriction and complications such as breath stacking (auto-PEEP [positive end-expiratory pressure]) and barotrauma. Although endotracheal intubation introduces risks, elective intubation should be performed if the asthmatic patient deteriorates despite aggressive management. Rapid sequence intubation is the technique of choice. The provider should use the largest endotracheal tube available IV-140 Circulation December 13, 2005 (usually 8 or 9 mm) to decrease airway resistance. Immedi- ately after intubation, confirm endotracheal tube placement by clinical examination and a device (eg, exhaled CO 2 detector) and obtain a chest radiograph. Troubleshooting After Intubation When severe bronchoconstriction is present, breath stacking (so-called auto-PEEP) can develop during positive-pressure ventilation, leading to complications such as hyperinflation, tension pneumothorax, and hypotension. During manual or mechanical ventilation use a slower respiratory rate (eg, 6 to 10 breaths per minute) with smaller tidal volumes (eg, 6 to 8 mL/kg), 34 shorter inspiratory time (eg, adult inspiratory flow rate 80 to 100 mL/min), and longer expiratory time (eg, inspiratory to expiratory ratio 1:4 or 1:5) than would typically be provided to nonasthmatic patients. Mild hypoventilation (permissive hypercapnia) reduces the risk of barotrauma. Hypercapnia is typically well tolerated. 35 Sedation is often required to optimize ventilation and mini- mize barotrauma after intubation. Delivery of inhaled medi- cations may be inadequate before intubation, so continue to administer inhaled albuterol treatments through the endotra- cheal tube. Four common causes of acute deterioration in any intu- bated patient are recalled by the mnemonic DOPE (tube Displacement, tube Obstruction, Pneumothorax, and Equip- ment failure). This mnemonic still holds in the patient with severe asthma. If the patient with asthma deteriorates or is difficult to ventilate, verify endotracheal tube position, eliminate tube obstruction (eliminate any mucous plugs and kinks), and rule out (or decompress) a pneumothorax. Only experienced providers should perform needle decompression or insertion of a chest tube for pneumothorax. Check the ventilator circuit for leaks or malfunction. High end-expiratory pressure can be quickly reduced by separating the patient from the ventilator circuit; this will allow PEEP to dissipate during passive exhalation. To minimize auto-PEEP, decrease inhalation time (this increases exhalation time), decrease the respiratory rate by 2 breaths per minute, and reduce the tidal volume to 3 to 5 mL/kg. Continue treatment with inhaled albuterol. Cardiac Arrest in the Asthmatic Patient When the asthmatic patient experiences a cardiac arrest, the provider may be concerned about modifications to the ACLS guidelines. There is inadequate evidence to recommend for or against the use of heliox during cardiac arrest (Class Indeter- minate). 36 There is insufficient evidence to recommend com- pression of the chest wall to relieve gas trapping if dynamic hyperinflation occurs. 37 Summary When treating patients with severe asthma, providers should closely monitor patients to detect further deterioration or development of complications. When there is no improve- ment and intubation is required, these patients require the care of experienced providers in an intensive care setting. 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