Q4 Urgent Caring- Management of Acute Asthma Exacerbations in Urgent Care

EB Medicine

Treatment

Oxygen

Oxygen is the first-line treatment agent in the management of hypoxic patients with undifferentiated dyspnea who have low saturations at the initial assessment. Judicious use of oxygen is recommended per Global Initiative for Asthma guidelines to achieve target oxygen saturation (SpO2) levels of 93% to 95% for adults with asthma.29 Hyperoxia can have deleterious effects, and controlled oxygen therapy is associated with lower mortality.13,29,32,33 Oxygen can be administered via nasal cannula or mask with or without a rebreathing device, depending on patient preference, tolerance, and saturations during the initial assessment phase. 

Pharmacologic Agents

First-line medications for acute asthma exacerbations are SABAs, anticholinergics, and corticosteroids. Other medications should be considered as second- and third-line treatments. These pharmacologic agents are discussed in the following sections.

Beta Agonists

Inhaled SABAs, such as albuterol, are first-line medications for acute asthma exacerbations, and are safe in high doses.13 SABAs induce pulmonary smooth muscle relaxation, with a peak effect at 30 minutes.41 The deleterious effects of SABA are tachycardia, tremors, and anxiety. Levalbuterol, the active enantiomer of albuterol, was not found to have any significant clinical advantages despite its higher cost, and it has largely fallen out of use.34

The 2023 report of the Global Initiative for Asthma, Global Strategy for Asthma Management and Prevention, 2023, recommends inhaled corticosteroids with long-acting beta agonists (LABAs) in moderate to severe asthma exacerbations.29

Metered-Dose Inhalers Versus Nebulizers

Multiple studies have evaluated the efficacy of metered-dose inhalers (MDIs) and nebulizer treatment to determine the best mode of delivery. A Cochrane review analyzed 39 trials to compare efficacy of inhaled beta-2 agonist therapy delivered via MDI with spacer versus nebulization. The review demonstrated that MDI with spacer therapy, compared to nebulization, was not associated with a significant difference in hospital admission rates or length of stay for adults with mild to moderate asthma exacerbation. In children, the length of stay, tremor development, and pulse rate were significantly lower when using MDI with spacer compared to nebulizer treatment. The quality of this evidence was noted to be moderate.35 The risk for transmission of respiratory pathogens also appears to be greater with the use of nebulization.36 Given current health precautions with COVID-19 and resource utilization, we recommend use of MDI with spacer for Urgent Care treatment, if readily available, for patients with mild to moderate asthma.

Intermittent Versus Continuous Nebulizer Treatments

Evidence shows that continuous beta agonist therapy may reduce the rate of hospitalization and improve pulmonary function in moderate to severe exacerbations.33,37,38 A study of children hospitalized for severe asthma exacerbation demonstrated that continuous treatments were more successful than intermittent nebulization.39 For adults, continuous nebulization is done by giving 5 to 10 mg of albuterol over 1 hour, as opposed to intermittent dosing of 2.5 mg every 30 minutes. Side effects may include nervousness, shakiness, headache, throat or nasal irritation and tachycardia. We recommend the use of continuous nebulization as safe and effective treatment for moderate to severe asthma exacerbations, while considering and setting up transport to the ED for continued management and monitoring.

Anticholinergics

Inhaled anticholinergic medications promote smooth-muscle relaxation and bronchodilation.32 The most used anticholinergic medication is ipratropium, with an onset of action within 15 minutes. Current evidence suggests that patients with acute asthma exacerbation treated with short-acting anticholinergics combined with SABA, instead of monotherapy with SABA, have better improvement in pulmonary function and are less likely to be admitted to the hospital. This is particularly evident in patients with moderate to severe exacerbations.29,33,40 Pediatric asthma patients have also been found to benefit from combination therapy with short-acting anticholinergics and SABA.41 Patients receiving combination therapy may experience more adverse effects such as tremors, agitation, and palpitations;40 however, ipratropium has a good safety profile and has been shown to be efficacious when administered along with SABAs. We recommend the use of 1 ipratropium dose with the first SABA treatment in patients with moderate to severe asthma exacerbations. In suspected COVID-19 infection, we suggest MDI with spacer; otherwise, both nebulizer and MDI options are equally effective.

Corticosteroids

Systemic corticosteroids are an essential first-line component of acute asthma exacerbation management. They reduce airway inflammation and may be administered via IV, oral, or inhaled routes. Evidence suggests that IV, intramuscular (IM), and oral routes have equivalent effects and bioavailability in most patients. IM and oral administrations are typically readily available in the Urgent Care setting and are less expensive and invasive than IV administration.13,16,29,32 IM injections do carry some additional risks, including pain, infection, traumatic fat necrosis, hematoma, nerve injury, and muscle wasting. Oral administration is easy and effective, with fewer potential side effects than IM, if the patient can swallow and tolerate oral intake. Inhaled corticosteroids are considered a mainstay of treatment for chronic asthma but are not effective for acute exacerbations.42 A Cochrane review found that corticosteroids administered within 1 hour of presentation significantly reduced hospitalization rates, especially in patients with severe exacerbations.43 Continuing oral corticosteroids after discharge has been shown to reduce the rate of repeat ED and Urgent Care visits.13,26

The standard of care for patients discharged after presentation for acute asthma exacerbation has included 3 to 10 days of oral corticosteroids, usually prednisone or prednisolone.13,29 However, since 1997, multiple randomized controlled trials in the pediatric literature have demonstrated that 1 or 2 doses of oral dexamethasone are equivalent to a 5-day regimen of prednisone/prednisolone in preventing relapse.44,45 Dexamethasone has a longer half-life than prednisone (36-72 hours vs 12-36 hours), and is better tolerated, with a lower incidence of vomiting. A 2014 meta-analysis incorporating 6 of these pediatric studies demonstrated no difference in relative risk of relapse at any of the endpoints used in these studies (5 days, 10-14 days, or 30 days).44 Most recently, Cronin et al compared a single dose of oral dexamethasone to 5 days of prednisolone in children and found no difference in symptoms at day 4, or in rate of admission or return to a provider within 14 days.45 Both of these studies showed a lower rate of vomiting among patients in the dexamethasone arm.

Regarding adult patients, the literature is not as robust, although there have been several recent studies demonstrating equivalence of oral dexamethasone to prednisone. Kravitz et al compared 2 days of oral dexamethasone (1 dose in the ED and 1 dose 24 hours later) to 5 days of oral prednisone. They found no difference in relapse at 14 days and an earlier return to normal activities in the dexamethasone group.46 A noninferiority trial by Rehrer et al comparing 1 dose of oral dexamethasone, given in the ED, to 5 days of oral prednisone barely failed to demonstrate noninferiority of dexamethasone.47 The upper limit of the confidence interval favored prednisone by 8.6%, while the noninferiority margin was preset at 8%. Still, the authors concluded that the convenience to patients and improved compliance of 1 ED dose of dexamethasone would likely translate to equivalence of the 2 treatment regimens.           

We feel that the literature supports 1 or 2 doses of oral dexamethasone in pediatric patients as a viable option for patients discharged after an acute exacerbation. For adult patients, dexamethasone needs further study, but it can be considered an option for patients with mild exacerbations and good follow-up.

Magnesium Sulfate

Magnesium sulfate, although not available in most Urgent Care clinics, can treat asthma through anti-inflammatory effects, smooth muscle relaxation, and bronchodilation.48 It is generally administered intravenously and has a rapid onset of action and rapid renal clearance.49 A Cochrane review with a high quality of evidence illustrated that IV magnesium sulfate administered for acute exacerbations significantly reduced hospital admission rates in patients who did not respond adequately to standard treatment. It demonstrated a reduction of 7 hospital admissions for every 100 patients treated. Adverse effects reported consisted of flushing, fatigue, headache, and hypotension.50 Patients included in all studies were of at least moderate severity. Inhaled magnesium sulfate has shown potential benefit without serious adverse events;51 however, the efficacy of treatment remains uncertain.

Pediatric literature also demonstrates improvement with administration of magnesium sulfate. Multiple studies have demonstrated improvement in pulmonary function, reduced hospital admission rate, and shorter length of stay in pediatric patients treated with IV magnesium sulfate along with standard treatment. This treatment is typically provided during moderate to severe exacerbations.52-55 IV magnesium sulfate was also shown in one study to be cost-effective in the treatment of asthma exacerbations.56

Epinephrine

Epinephrine is a potent bronchodilator secondary to beta-2 agonist activity and may reduce mucus production, airway edema, and inflammation via alpha-1 agonism.40 Epinephrine may be considered in severe asthma, or under certain defined conditions such as exacerbations related to anaphylaxis or angioedema, by national and international consensus guidelines,13,29 but is not recommended for routine, first-line treatment. Many researchers and clinicians recommend that it be considered in severe, life-threatening asthma, by IM, nebulized, or IV route.32,57,58,59

Nonetheless, there is not a substantial body of high-quality evidence to support the addition of epinephrine to standard treatments in the management of severe asthma. A systematic review and meta-analysis of 38 studies, involving over 2200 patients, found no difference in rate of treatment failure for epinephrine by any route as compared to selective beta-2 agonists by any route.60 In addition, the researchers found a low certainty of evidence due to a high incidence of bias and high degree of heterogeneity of the studies. None of the studies evaluated the addition of IM epinephrine to standard treatments, and the 2 studies that evaluated subcutaneous epinephrine in addition to standard care found no evidence of added benefit.

Several studies have evaluated the risk for adverse events from parenteral epinephrine in the treatment of severe asthma.61-63 These studies found some minor adverse effects (anxiety, palpitations, nausea) and some episodes of transient, uncomplicated hypertension and/or tachycardia, but minimal incidence of clinically significant adverse effects. Each of these studies concluded that epinephrine was safe to use in severe asthma.

Given its favorable safety profile, we recommend the use of epinephrine (0.3-0.5 mg of 1 mg/mL concentration given IM into the anterolateral thigh) for severe, life-threatening asthma that is not responding to standard treatments, or if suspected to be related to anaphylaxis and/or angioedema. The IM route is preferred over the subcutaneous route.32,59 For patients who are profoundly hypotensive or refractory to IM treatment, IV epinephrine may be considered, at a dose of 5 to 20 mcg every 2 to 5 minutes, followed by an infusion of 0.1 to 0.5 mcg/kg/min.59 For this situation, referral and transfer via EMS to the nearest ED should be performed immediately. Additionally, we feel that further prospective studies are needed to evaluate the efficacy and safety profile of parenteral epinephrine in these patients.

Special Populations

Pregnant Patients

Asthma is the most common respiratory condition in pregnancy, affecting 5% to 8% of pregnancies in the United States and 8% to 13% worldwide.64,65 It is associated with increased risk for pregnancy-induced hypertension, pre-eclampsia, gestational diabetes, placenta previa, placental abruption, postpartum hemorrhage, preterm birth, and low birth weight.64-68 Poorly controlled asthma increases the likelihood of these complications.

Management of asthma in pregnancy is the same as for nonpregnant patients.69 None of the standard asthma medications has been shown to pose a risk to the fetus; however, it is estimated that up to 40% of pregnant patients are noncompliant with asthma treatments.65 Well-controlled asthma can lead to normal maternal and fetal outcomes, and it is incumbent on clinicians to manage pregnant asthma patients appropriately.66,70

Asthma Patients With COVID-19

According to the United States Centers for Disease Control and Prevention (CDC), “people with moderate to severe asthma may be at higher risk of getting very sick from COVID-19,” because COVID-19 can cause asthma attacks and possibly lead to pneumonia or acute respiratory disease.71 However, multiple studies have shown a low prevalence of asthma among patients with severe COVID-19, when compared to those with non-severe disease or the general population.72-75 Furthermore, studies have shown that patients with asthma and COVID-19 do not have higher rates of admission, ICU admission, or mortality.73,75-79

Although some have argued that the use of inhaled corticosteroids may lead to a decreased expression of the angiotensin converting enzyme 2 (ACE2) receptor, which is thought to be a major entry point of the virus into human cells, the clinical significance of this remains unclear.74,75,80 

References

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Excerpted from: Flax J, Wilson M, Ring H. Management of acute asthma exacerbations in Urgent Care. Evidence-Based Urgent Care. 2023 November;2(11):1-25. Reprinted with permission of EB Medicine.