Acute Exacerbation of Asthma Case File

Acute Exacerbation of Asthma Case File

Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS

Case 11

At 3 AM the paramedics call to inform you that they are en route to the emergency department with a 33-year-old asthmatic. As she is brought in, you immediately notice that she is struggling to breathe. Sweat pours from her face and body as her neck and chest heaves in an attempt to inhale another breath. Her efforts are ultimately futile as consciousness slips away and she becomes apneic.

⯈ What are your initial priorities in the management of this patient?

⯈ What are your standard treatment options in managing her emergency medical condition?

ANSWER TO CASE 11:

Acute Exacerbation of Asthma

Summary: This is a case of a 33-year-old woman experiencing a severe asthma attack. Respiratory arrest is imminent.

• Initial Priorities: The first priority in this patient’s management is addressing the ABCs (airway, breathing, circulation). Based on this presentation, immediate protection of her airway with rapid-sequence endotracheal intubation is indicated. Simultaneously, this patient should be placed on a cardiac monitor with automated blood pressure measurement, establishment of IV access, and continuous pulse oximetry.
• Standard treatment options: Basic treatment options include adrenergic agonists (eg, albuterol, terbutaline), anticholinergic agents, and corticosteroids. Intravenous magnesium sulfate is often given to patients with severe asthma exacerbations.

ANALYSIS

Objectives

1. Understand the pathophysiology of respiratory distress caused by acute asthma exacerbation.
2. Describe the key historical and physical examination features.
3. Be able to discuss treatment options for the patient with acute bronchospasm caused by asthma.

Considerations

This 33-year-old asthmatic patient has progressive respiratory difficulty until she becomes apneic. Regardless of the underlying etiology, airway and breathing are the most important initial concerns in any patient. Attention to the airway is critical, and in this case, rapid-sequence endotracheal intubation is the best option. Because airway issues may arise at any given time, the emergency room physician must be skilled, rehearsed, and have equipment to perform endotracheal intubation at any given time. Protection of the airway and mechanical ventilation is the best therapy in this instance. Administration of beta-agonist agents, corticosteroids, anticholinergic agents, and search for the trigger are likewise important.

Approach To:

Asthma

Epidemiology and Pathophysiology

In the United States, asthma accounts for more than 2 million emergency department (ED) visits, 456,000 hospitalizations, and 3500 deaths each year. Overall, between 4% and 8% of all adults carry a diagnosis of asthma, with a higher prevalence reported in children, the elderly, and in Hispanic and African Americans. It is the most common chronic disease in children and adolescents and the third leading cause of preventable hospitalizations in the United States. Asthma results in more than 10 million lost school and workdays per year, and results in $30 billion of medical expenses per year.

Asthma is considered a chronic inflammatory disorder of the airways. It consists of narrowing of the airway leading to reduced airflow and can be induced by smooth muscle contraction, thickening of the airway wall, and the presence of secretions within the airway lumen in response to an inciting allergen. In susceptible individuals, these changes result in recurrent episodes of wheezing, breathlessness, chest tightness, and cough.

Two distinct phases of asthma have been described. The early (or immediate) phase of asthma consists of acute airway hyperresponsiveness and reversible bronchoconstriction. Following allergen challenge, the lungs begin to constrict within 10 minutes. Peak bronchoconstriction occurs at 30 minutes and either spontaneously or with treatment resolves within 1 to 3 hours. With continued allergen challenge or with refractory bronchoconstriction, this initial phase can progress into the late phase of asthma. This late (or delayed) phase of asthma begins 3 to 4 hours after the allergen challenge and constitutes the inflammatory component seen with acute asthma. Inflammatory cell recruitment, bronchial edema, mucoserous secretion, and further bronchoconstriction all play key roles in the development and propagation of late-phase asthma. Whereas beta-2 agonists target the immediate phase of asthma, corticosteroids target the delayed phase.

Diagnosis

The typical asthma exacerbation is characterized by cough, chest tightness, dyspnea, and wheezing in a patient with a known asthma history. Formal diagnosis is made by spirometry with 75% of asthmatics diagnosed before age 7. Although wheezing characterizes airway obstruction and is often thought of as the hallmark finding in asthma, it is not specific to asthma, and can be absent during severe asthma exacerbations. The history and physical examination should focus on excluding other diagnoses while evaluating the severity of the current asthma exacerbation. Key features to elicit are the nature and time course of the symptoms, precipitating triggers (Table 11–1), use of medication prior to arrival, and any high-risk historical features (Table 11–2).

The evaluation of an asthmatic patient begins with the general appearance of the patient. Those who are extremely anxious or drowsy, unable to speak in full sentences secondary to respiratory distress, or are using accessory muscles of inspiration (tripod position/inability to lay supine) are at significant risk for rapid decompensation. Additional worrisome features are signs of central cyanosis, hypoxia (pulse oximetry <90%), significant tachypnea (>30 breaths per minute), tachycardia, diaphoresis, diffuse or absent wheezing, and poor air entry on pulmonary examination.

Although extremely helpful, physical examination findings are not sensitive indicators of a clinically severe exacerbation. Since asthmatics have a propensity for deteriorating quickly, an objective measure of severity should be sought whenever possible. Bedside testing that measures peak expiratory flow rate (PEFR) or 

fractional expiratory volume at 1 second (FEV1) are simple, inexpensive ways of measuring the severity of airway obstruction and are commonly used to monitor response to treatment in the ED. Severe asthma is defined as an FEV1 of less than 50% of predicted (typically <200 L/min in an adult) or one’s own personal best measurement.

Routine laboratory investigations (eg, complete blood count, basic metabolic panel), arterial blood gas (ABG) analysis, chest radiography, and cardiac monitoring are not required in the uncomplicated asthmatic. Table 11–3 suggests indications for each of these modalities.

MANAGEMENT

Immediate priorities in the management of all asthma patients include an initial assessment of the patient’s airway, breathing, and circulation status. Patients in extremis require placement of peripheral intravenous lines, continuous supplemental oxygen therapy, and cardiac monitoring. While these interventions are underway, the physician should ascertain a history, perform a physical examination, and initiate appropriate therapy.

Oxygen, Compressed Air, and Heliox

Oxygen should be provided to maintain a pulse oximetry reading of at least 90% in adults and at least 95% in infants, pregnant women, and patients with coexisting heart disease. Oxygen is often used as the delivery vehicle for nebulized medications, although compressed air and helium-oxygen mixtures (heliox) can also be used.

Heliox mixtures produce a more laminar airflow and potentially deliver nebulized particles to more distal airways, but they have not been shown to consistently lead to improved ED outcomes for all asthmatic patients. A systematic review concluded that heliox may be beneficial only in patients who present with severe asthma that is refractory to initial treatment.

Adrenergic Agents

Inhaled albuterol, through nebulization or metered-dose inhaler (MDI) with spacer device, is the mainstay of treatment for acute asthma. Typically 2.5 to 5 mg of albuterol is intermittently nebulized every 15 to 20 minutes for the first hour of therapy and then repeated every 30 minutes thereafter for 1 to 2 more hours. Continuous nebulization with higher doses (10-20 mg/h) of albuterol benefits severe asthmatics. Beta-2 agonists bind pulmonary receptors and activate adenyl cyclase which results in an increase in intracellular cyclic adenosine monophosphate (cAMP). This results in a drop in myoplasmic calcium and subsequent bronchial smooth-muscle relaxation. In addition, beta-2 agonists are thought to have some anti-inflammatory properties by inhibiting inflammatory mediator release. Side effects of these agents are generally mild and include tachycardia, nervousness, and shakiness or jitteriness.

Alternatively, albuterol can be administered with an MDI and spacer device. In the ED, patients can receive 4 to 8 puffs every 15 to 20 minutes for the first hour of therapy and then every 30 minutes thereafter for 1 to 2 more hours. MDI with spacer device therapy is therapeutically equivalent to nebulizer therapy in adults and may be more efficacious than nebulizer therapy in children as less medication is lost to the environment. Implementation of MDI with spacer device therapy for asthmatics in the ED is also associated with decreased health care cost.

Although inhalation therapy is optimal, occasionally patients with severe obstruction or who cannot tolerate inhalation therapy (eg, children) are given subcutaneous administration of epinephrine or terbutaline. Epinephrine is given in a dose of 0.3 to 0.5 mg subcutaneously every 20 minutes to a maximal combined total dose of 1 mg. Terbutaline is given 0.25 mg subcutaneously every 20 minutes up to a maximum of three doses. Generally, terbutaline is preferable because of its beta-2 selectivity and fewer cardiac side effects.

Levalbuterol, the R-isomer of racemic albuterol, was developed because in vitro studies suggested that the S-isomer may have deleterious effects on airway smooth muscle. However, randomized trials have not shown a significant clinical advantage of levalbuterol over racemic albuterol for the treatment of acute asthma in the emergency department. National asthma treatment guidelines currently consider levalbuterol equally safe and effective to racemic albuterol and endorse its use for the treatment of acute asthma exacerbations.

Anticholinergic Agents

When added to albuterol, anticholinergic agents lead to a modest improvement in pulmonary function and decrease the admission rate in patients with moderate to severe asthma exacerbations. Anticholinergics decrease intracellular cyclic guanosine monophosphate (cGMP) concentrations, which reduce vagal nerve-mediated bronchoconstriction on medium- and larger-sized airways. Additionally, anticholinergic agents may have some minor anti-inflammatory properties that help to stabilize capillary permeability and inhibit mucous secretion. The typical dose for ipratropium bromide is two puffs from a MDI with spacer device, or 0.5 mL of the 0.02% solution. Anticholinergics can be combined with beta agonists in nebulization devices and should be given to those not responding to initial beta-agonist therapy and those with severe airway obstruction. Since there is little systemic absorption, inhaled anticholinergics are associated with few side effects.

Corticosteroids

Corticosteroids have been used to treat chronic asthma since 1950 and acute exacerbations of the disease since 1956. Although a tremendous amount of research has been done on the value of corticosteroids in asthma, many fundamental issues have yet to be resolved, such as the optimal dose, route, and timing of steroids. It is generally agreed that corticosteroids should be initiated early in the treatment of the following cases:

• Acute asthma in patients with moderate/severe asthma attack
• Worsening asthma over many days (>3 days)
• Mild asthma not responding to initial bronchodilator therapy or asthma that develops despite daily inhaled corticosteroid use.

Some authors believe that more liberal use of corticosteroids is warranted and advocate steroids for any patient whose symptoms fail to resolve with a single albuterol treatment. Even more liberal asthmatologists prefer that steroids be given for every asthma patient who is sick enough to warrant ED evaluation.

Steroids act on the delayed phase of asthma and modulate the inflammatory response. They have been shown to improve pulmonary function, decrease the rate of hospital admission, and decrease the rate of relapse in patients that receive them early in their ED treatment course. Oral administration of prednisone (dose 40-60 mg) is usually preferred to intravenous methylprednisolone (dose 125 mg), because it is less invasive and the effects are equivalent. Intravenous steroids, however, should be administered to patients with severe respiratory distress who are too dyspneic to swallow, patients who are vomiting, or patients who are agitated or drowsy. For patients who will be discharged, a single intramuscular dose of methylprednisolone (dose 160 mg) may be given when there is a history of medication noncompliance. A 2-day course of oral dexamethasone (dose 16 mg) is also an option because it has been shown to be equivalent to five days of prednisone. Alternative steroids include hydrocortisone 150 to 200 mg IV, dexamethasone 6 to 10 mg IV, or oral dexamethasone 0.6 mg/kg (maximum dose 16 mg) in pediatric patients.

Leukotriene Antagonists

The development of leukotriene antagonists represents an important advancement in the treatment of chronic asthma. Studies involving zileuton (Zyflo Filmtab), zafirlukast (Accolate), and montelukast (Singulair) demonstrate that their daily use over the course of several months can lead to improvement in pulmonary function and decrease in asthma symptomatology. However, the role of leukotriene antagonists in the treatment of acute asthma exacerbations remains unclear. A randomized study of intravenous montelukast showed that it significantly improved FEV1 when added to standard asthma therapy, but this improvement in lung function did not translate to lower hospitalization rates. At this time, asthma treatment guidelines recommend the use of leukotriene antagonists only in the management of chronic asthma.

Magnesium

Although no benefit has been shown in mild to moderate asthmatics, magnesium sulfate given intravenously at dosages of 2 to 4 g benefits asthmatics with severe airway obstruction. Magnesium is thought to compete with calcium for entry into smooth muscle, inhibit the release of calcium from the sarcoplasmic reticulum, prevent acetylcholine release from nerve endings, and inhibit mast cell release of histamine. Additionally, there is some evidence that magnesium may directly inhibit smooth muscle contraction, but this is controversial. The onset of magnesium is quick and effects can be seen 2 to 5 minutes after initiation of therapy. The effects are short lived and diminish quickly when the infusion is stopped. The dose of magnesium is 2 to 4 g IV in adults and 30 to 70 mg/kg IV in children given over 10 to 15 minutes. Magnesium has minimal side effects. The most commonly reported are hypotension, a flushing sensation, and malaise. It is contraindicated in renal failure and in cases of hypermagnesemia as it can cause significant muscle weakness.

Other Agents—Methylxanthines, Antibiotics

The marginal benefit, significant side effects, and difficulty achieving a therapeutic dose of theophylline argue against its routine use in acute asthma. A systematic review concluded that the addition of aminophylline to treatment with beta agonists and glucocorticoids improved lung function, but did not significantly reduce symptoms or length of hospital stay. Therefore, methylxanthines are not recommended in the treatment of acute asthma exacerbations. The routine administration of antibiotics has also not been shown to decrease symptomatology in asthma patients without concurrent bacterial lower respiratory infection or sinusitis.

Positive Pressure Ventilation

Positive pressure ventilation (PPV), with either invasive or noninvasive methods, is indicated for patients with respiratory failure or impending failure who are not responsive to therapy. Several studies have suggested that bi-level positive airway pressure (BiPAP) may be beneficial in severe asthma exacerbations. For example, a randomized trial enrolled severe asthmatics (defined as FEV1 <60% and RR>30) to receive BiPAP and found significant improvements in pulmonary function and reduced rates of hospitalization. Severe asthmatics with impending respiratory failure should receive a trial of BiPAP prior to being intubated. The BiPAP machine should be set at inspiratory pressure 8 to 15 cm H2O and expiratory pressure 3 to 5 cm H2O. Patients who fail to improve over 30 to 60 minutes will likely require intubation. Furthermore, contrary to prior teaching, a short trial (30 minutes) of BiPAP is considered acceptable for mild to moderate altered level of consciousness attributed to hypercapnea.

Immediate rapid-sequence endotracheal intubation should be reserved for unconscious or near-comatose patients with respiratory failure. In an awake patient, an appropriate induction agent (eg, ketamine) and paralytic agent (eg, succinylcholine) should be used prior to intubation. Ketamine is the induction agent of choice because it stimulates the release of catecholamines and causes relaxation of bronchial smooth muscle, leading to bronchodilation. Numerous case reports have also demonstrated that a ketamine infusion may be useful when severe asthmatics fail to respond to conventional treatments. Ketamine is given as an intravenous bolus of 1 mg/kg, followed by a continuous infusion of 0.5 to 2 mg/kg/h.

Once an asthmatic patient is intubated, the ventilator should be set to promote the goal of permissive hypercapnea which aims at minimizing dynamic hyperinflation (ie, breath stacking or auto-PEEP [positive end-expiratory pressure]) with low tidal volumes, and increased time for expiration, while limiting plateau pressures. It is critical to recognize that mechanically ventilated asthmatic patients are at high risk for hyperinflation and auto-PEEP which can result in life threatening complications such as tension pneumothorax or cardiac arrest. Suggested initial settings are Assist Control mode at a respiratory rate of 8 to 10 breaths per minute, tidal volume 6 to 8 mL/kg, no extrinsic PEEP, inspiratory-to-expiratory (I/E) ratio of 1:4, and an inspiratory flow rate of 80 to 100 L/min. To prevent barotrauma, plateau pressures should not exceed 30 cm H2O. Following initiation of PPV, blood-gas analysis can be used to modify ventilator or BiPAP settings.

ADMISSION/DISCHARGE CRITERIA

Acute asthma is a heterogeneous condition and as such patients should be individualized when it comes to disposition decisions. Patients who respond well to therapy by improved subjective and objective criteria (eg, symptoms resolved, normal or near-normal pulmonary examination) are suitable candidates for discharge. Patients should be on room air and moving about the emergency department before finalizing the decision to discharge the patient. An improvement of PEFR or FEV1 to greater than 70% predicted or personal best can also be used as a sign of objective improvement. Hospital admission should be considered in patients that fail to respond to therapy (ie, PEFR or FEV1 < 50% predicted) after 4 to 6 hours of treatment or patients with partial response to therapy (ie, PEFR or FEV1 between 50% and 70% predicted) and one or all of the following:

1. New-onset asthma
2. Multiple prior hospitalizations or ED visits
3. Have comorbidity from coronary artery disease
4. Have significant medical or social issues that impair access to health care, personal judgment, or understanding of their disease.

Asthmatics who are discharged from the ED should receive albuterol, an MDI spacer device, and a 5- to 10-day course of oral steroids. Most patients should be treated for at least 1 week, but can stop their oral steroids based on resolutions of their symptoms and self-monitored peak flow values. Tapering is not necessary if the duration of steroid treatment is less than 3 weeks, if inhaled steroids are concomitantly prescribed for preventative ongoing therapy, or as long as the patient has not recently been on steroid therapy.

Inhaled corticosteroids (ICS) should be prescribed to anyone with frequent beta-agonist MDI use and is symptomatic enough to warrant urgent medical evaluation. Several studies have demonstrated that ICS improve lung function, diminish symptoms, and decrease “rescue use” of beta agonists. Beneficial effects of ICS can be observed after a single dose and therapeutic effects are achieved with chronic administration. Furthermore, one can initiate treatment alongside oral steroids without fear of added systemic toxicity. Recent studies have documented a significant reduction in relapse rates when combining oral and inhaled steroids. For patients who continue to have poorly controlled asthma and recurrent exacerbations despite maximal therapy, other medications may be added such as long-acting inhaled beta agonists, oral leukotriene antagonists, and omalizumab (a monoclonal anti-IgE antibody).

While awaiting discharge, MDI with spacer device technique should be reviewed with the patient, and the patient should be instructed on how to monitor peak flow readings at home. Additionally, patients should be educated about the common asthma precipitants and how to avoid them, as well as receive written and verbal instructions on when to return to the ED. Finally, patients should be referred for a follow-up medical appointment in a timely manner. Arranging ongoing care with an asthma specialist or a clinic focusing on asthma patients is more likely to reduce subsequent emergency department visits. Patients who are unable to follow up with their primary physician can be instructed to return to the ED for a recheck of their symptoms.

COMPREHENSION QUESTIONS

11.1 A 24-year-old man is brought into the ED complaining of an exacerbation of his asthma. Which of the following is the most appropriate method of assessing the severity of his disease?

A. Spirometry

B. Measurement of the diffusion capacity of the lungs

C. Measurement of the peak expiratory flow

D. Measurement of the alveoli oxygen tension

11.2 A 19-year-old woman is admitted to the hospital for an exacerbation of asthma likely precipitated by pollen and colder weather. Her inpatient regimen includes both intravenous and inhalant medications. Which of the following medications is most likely to be used as part of discharge plan?

A. Theophylline

B. Antibiotics

C. Magnesium

D. Histamines

E. Corticosteroids

11.3 Which of the following initial ventilator settings is appropriate for intubated asthmatics?

A. IMV mode, rate 16, tidal volume 6 to 8 mL/kg

B. IMV mode, rate 16, tidal volume 10 to 12 mL/kg

C. AC mode, rate 8 to 10, tidal volume 6 to 8 mL/kg

D. AC mode, rate 8 to 10, tidal volume 10 to 12 mL/kg

E. AC mode, rate 16, tidal volume 6 to 8 mL/kg

ANSWERS

11.1 C. The peak expiratory flow is a reliable and fairly accurate method of assessing asthma severity. Spirometry, although providing important information, is rarely available in the ED.

11.2 E. Corticosteroids are often used after a hospitalization. Other standard medications include beta-agonists and oral leukotriene antagonists. None of the other medications are used routinely for discharged asthma patients.

11.3 C. The initial settings for patients with obstructive lung disease should be AC mode, rate 8 to 10, tidal volume 6 to 8 mL/kg. Low volumes and small tidal volumes are used to prevent air stacking and barotrauma.

CLINICAL PEARLS

⯈ Initiate therapy with albuterol while obtaining history and performing a physical examination for patients with significant asthma.

⯈ Glucocorticosteroids should be administered early for asthmatic exacerbations and continued for at least 1 week.

⯈ Measure peak flow to help assess asthma severity and monitor progression during treatment.

⯈ Use lower than traditional ventilator settings to prevent barotrauma in the intubated asthmatic.

⯈ Most asthmatics should be discharged from the ED with inhaled corticosteroids for ongoing preventative therapy.

⯈ The individual who presents with an initial episode of “wheezing” may have etiologies other than asthma, for example, foreign body, pneumonia, or congestive heart failure.

⯈ Absence of wheezing can sometimes be misleading in the individual in extremis because of very little air movement.

References

Akinbami LJ, Moorman JE, Liu X. Asthma prevalence, health care use, and mortality: United States, 2005-2009. National Health Statistics 2011:32. 

Camargo CA, Rachelefsky G, Schatz M. Managing asthma exacerbations in the emergency department: Summary of the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines for the management of asthma exacerbations. J Allergy Clin Immunol. 2009;124:S5-S14. 

Keenan SP, Sinuff T, Cook DJ, et. al. Does noninvasive positive pressure ventilation improve outcome in acute hypoxemia respiratory failure? A systematic review. Crit Care Med. 2004;32(12):2516-2523. 

Krishnan JA, Davis SQ, Naureckas ET, et al. An umbrella review: Corticosteroid therapy for adults with acute asthma. Am J Med. 2009;122(11):977-991. 

National Heart, Lung, and Bood Institute, National Asthma Education Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma: full report 2007. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf). Accessed March 1, 2011. 

Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: A systematic review with meta-analysis. Thorax. 2005;60:740-746. 

Schatz M, Rachelefsky G, Krishnan JA. Follow-up after acute asthma episodes: What improves future outcomes? J Emerg Med. 2009;37:S42-S50.

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