Evidence Based Management of Severe Acute Asthma in Young Children Suzanne Schuh, MD, FRCP(C), FAAP, ABPEM
Research Director, Division of Paediatric Emergency Department
The Hospital for Sick Children, Toronto, Canada
Professor of Pediatrics, University of Toronto, Toronto, Canada
A definitive diagnosis of asthma is difficult to make in young children. While there are children with recurrent wheeze who subsequently do not develop signs and symptoms that match the criteria for the accepted diagnosis of asthma, their acute care in the Emergency Department (ED) is the same as that for their true asthmatic counterparts. Some of the common issues facing the ED physicians are a) what young children with acute recurrent wheezing require supplemental oxygen? b) what are the barriers to implementation of the use of the MDIs in the paediatric EDs? c) what corticosteroids should be used in the ED? d) what other agents should be considered in children not responding to standard therapy? Most literature related to oxygen therapy in young wheezing children comes from the population with bronchiolitis but much of it is likely relevant to infants with recurrent wheezing/asthma as well. Transcutaneous oximetry has been routinely used since the mid 1980s and may have led to new criteria for hospitalization. Since then, the rate of hospitalization for bronchiolitis has increased by nearly 250% but mortality has remained unchanged(1). Several experts hypothesize that the use of frequent/ continuous oximetry as well as its inconsistent interpretation with respect to when to initiate oxygen therapy may be largely responsible for this trend(1‐3). There is little evidence as to when supplemental oxygen is required, with guidelines ranging from 90%-94%(4-8), without evidence delineating the associated risks and benefits. As a result, many infants with mild distress with saturations mildly diminished in the lower 90s are admitted for oxygen therapy, regardless of the degree of respiratory distress, duration of desaturation, or state of wakefulness. However, mild hypoxemia in bronchiolitis need not be accompanied by significantly increased work of breathing. Oxygen saturation seems to have emerged as an overriding criterion for hospitalization from the ED and for discharge from the inpatient ward(9). A survey of the American Academy of Pediatrics (AAP) members on their treatment preferences in bronchiolitis found that a minimal and physiologically insignificant difference in oxygen saturation between 92% and 94%(10, 11) with identical respiratory rates produces a two-fold increase in intended hospitalization rates(9). This study illustrates that small differences in oxygen saturation have major impact on disposition. Recent AAP guidelines on bronchiolitis management suggest that previously healthy children with saturation 90% or higher are unlikely to benefit from supplemental oxygen(12). However, this
recommendation consists of an expert consensus based on physiological principles and has not been prospectively validated.
It is well known that bronchodilators delivered by metered dose inhalers (MDIs) with valved holding chambers (VHCs) are at least as effective as those delivered by nebulizers in children with acute asthma. A recent Cochrane review shows that the use of MDIs results in a shorter length of ED stay, smaller increase in heart rate and a trend toward lower hospitalization rates compared to the nebulizer(13). Furthermore, the MDIs are preferred by both children and parents over nebulizer in the paediatric ED setting(14). Young children have more rapid respiratory rates, lower inspiratory flows and smaller airways compared to their older counterparts, and breathe through the nose, limiting drug penetration into the lungs and necessitating relatively large doses of β2 agonists(15, 16). The lung deposition of salbutamol from both the MDI and nebulizer is significantly lower in younger children than in older children(16-18). Therefore, in children weighing less than 15 kg the minimum recommended dose of salbutamol via nebulizer is 2.5 mg(18, 19). The salbutamol dose for via an MDI needed to accomplish a comparable lung deposition is approximately six times lower, at 400 mcg(20, 21). The burden of non- pulmonary side effects of therapy via an MDI is lower than that associated with the nebulizers, since the VHC reduces drug deposition in the upper airway(22). Despite this evidence, the majority of paediatric EDs in Canada and the United States have not adopted the MDIs for acute asthma treatment(23). A recent survey of 10 Canadian paediatric EDs shows that at 2 sites then MDIs are never used and at 6 sites they are used only rarely(24). The major perceived barriers to implementation are the safety and feasibility of reusing VHCs, the cost to the ED, parental expectations, nursing workload and lack of a physician champion to implement the change. Interestingly, the staff at the 2 user sites found they were able to reuse and sterilize VHCs to keep the costs down, and that the parents are more satisfied with the MDIs which is also supported by the literature(25, 26). However, the relative nursing time and associated costs involved in providing the MDI versus nebulizer treatment needs to be studied, as does the safety of sterilizing VHCs. It is also documented that inhaled ipratropium bromide improves lung function and decreases hospitalizations in children with severe disease(27, 28). However, we do not know if ipratropium provides any additional benefit when salbutamol is delivered by the MDI/VHC since near maximal bronchodilation may be achieved in many children with salbutamol alone. Systemic corticosteroids used in severe asthma improve symptoms, airway obstruction and oxygenation, and decrease likelihood of admission to hospital from the ED(29). As the oral and intravenous routes of administration are equally effective(30), IV therapy is only indicated in children with persistent vomiting and with very severe disease. In some patients corticosteroids work as early as 2 hours after administration since they upregulate the ß2 receptors and decrease airway edema(31). Oral prednisone/prednisolone has a bitter taste and its use frequently results in vomiting. However dexamethasone
syrup is a very palatable alternative for use in the ED. Dexamethasone has a biologic half-life of 48-54 hours(32) and on a per milligram basis is six times more potent than prednisolone. Thus a dose of 0.3 mg/kg of dexamethasone is roughly equivalent to 2.0 mg/kg of prednisone/prednisolone. Studies in children with both severe and mild acute asthma have shown that these agents are less effective than oral corticosteroids(33, 34). Inhaled corticosteroids alone should not be used for stabilization of acute asthma exacerbations in children; systemic corticosteroids remain the therapy of choice in these situations(35). Intravenous magnesium is a useful and safe adjunct in children with critical asthma severity and in those not responding well to the aforementioned pharmacotherapy. Magnesium acts primarily by inhibition of calcium release from sarcoplasmic reticulum and attendant relaxation of airway smooth muscle as well as by reduction of the neutrophilic burst associated with the inflammatory response(36-38). A recent meta-analysis showed a significant improvement in respiratory function and a 30% decrease in hospitalizations compared to placebo(39). Although the response to magnesium usually occurs quickly, its half-life is short and the infusion may have to be repeated. The authors recommend this agent as a standard treatment for severe asthma not responding to the initial bronchodilator therapy which is not when it is usually considered. A more relevant question may be if magnesium prevents high-risk outcomes such as ICU admissions, IV salbutamol therapy or ventilation in patients not responding to corticosteroids. The evidence regarding the efficacy of inhaled magnesium in acute asthma is inconclusive since only two small studies have enrolled children exclusively and they suggest non-significant impact on outcomes(40, 41). Therefore this agent cannot be currently recommended. Patients who are refractory to treatment with corticosteroids and magnesium are candidates for IV salbutamol therapy. This mode of therapy is usually given in the ICU setting(42, 43). IV salbutamol is usually administered together with inhaled salbutamol, either as a trial to prevent intubation and ventilation, or as an adjunct to ventilator therapy(44). There is currently no evidence that IV salbutamol should routinely replace the use of inhaled salbutamol in the ED management of severe asthma, and it should only be used in patients not responding to inhaled salbutamol(45). Children experiencing persistent respiratory distress 4 hours after corticosteroids usually require hospitalization, as do those with baseline oxygen saturations below 89%(46). Consideration for extended observation/hospitalization should also be given in patients whose parents have initiated hourly inhaled salbutamol due to lack of response and those already on systemic corticosteroids prior to arrival, children with chronic poor asthma control and those with previous ICU admissions. The ED staff also need to educate patients and parents about the proper use of the MDI/VHC, outline therapeutic plan and initiate follow up. Salbutamol via MDI/VHC can be continued up to every 4 hours for several days, 400 mcg per dose is likely advisable for 24-48 hours after discharge from the ED to provide optimal bronchodilation. Prednisone/prednisolone can be used daily for 5-7 days, tapering is usually not necessary.
Two consecutive daily dexamethasone doses offer comparable benefits to a six-day course of prednisone, with fewer side effects and greater compliance(47). Inhaled corticosteroids alone do not provide adequate benefit after discharge. However, they should be used as prophylactic agents for several weeks to prevent further exacerbations (48). References:
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