2. suzanne schuh

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

Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 1999;282(15):1440-6. 2. Langley JM, LeBlanc JC, Smith B, Wang EE. Increasing incidence of hospitalization for bronchiolitis among Canadian children, 1980-2000. J Infect Dis 2003;188(11):1764-7. 3. Smyth RL, Openshaw PJ. Bronchiolitis. Lancet 2006;368(9532):312-22. Bajaj L, Turner CG, Bothner J. A randomized trial of home oxygen therapy from the emergency department for acute bronchiolitis. Pediatrics 2006;117(3):633-40. 5. Adcock PM, Sanders CL, Marshall GS. Standardizing the care of bronchiolitis. Arch Pediatr Adolesc Med 1998;152(8):739-44. 6. Rodriguez WJ. Management strategies for respiratory syncytial virus infections in infants. J Pediatr 1999;135(2 Pt 2):45-50. 7. Harrison AM, Boeing NM, Domachowske JB, Piedmonte MR, Kanter RK. Effect of RSV bronchiolitis practice guidelines on resource utilization. Clin Pediatr (Phila) 2001;40(9):489-95. 8. Kotagal UR, Robbins JM, Kini NM, Schoettker PJ, Atherton HD, Kirschbaum MS. Impact of a bronchiolitis guideline: a multisite demonstration project. Chest 2002;121(6):1789-97. 9. Mallory MD, Shay DK, Garrett J, Bordley WC. Bronchiolitis management preferences and the influence of pulse oximetry and respiratory rate on the decision to admit. Pediatrics 2003;111(1):e45-51. 10. Rebuck AS, Chapman KR. The P90 as a clinically relevant landmark on the oxyhemoglobin dissociation curve. Am Rev Respir Dis 1988;137(4):962-3. 11. Barker SJ. Pulse Oximetry. In: Anesthesia Equipment: Principles and Applications. St. Louis, MO: Ehrenwerth J, Eisenkraft JB, eds.; 1993. p. 249-63. 12. Diagnosis and management of bronchiolitis. Pediatrics 2006;118(4):1774-93. Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev 2006(2):CD000052. 14. Cotterell EM, Gazarian M, Henry RL, O'Meara MW, Wales SR. Child and parent satisfaction with the use of spacer devices in acute asthma. J Paediatr Child Health 2002;38(6):604-7. 15. Newhouse MT, Dolovich MB. Control of asthma by aerosols. N Engl J Med Tal A, Golan H, Grauer N, Aviram M, Albin D, Quastel MR. Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction. J Pediatr 1996;128(4):479-84. 17. Chua HL, Collis GG, Newbury AM, Chan K, Bower GD, Sly PD, et al. The influence of age on aerosol deposition in children with cystic fibrosis. Eur Respir J 1994;7(12):2185-91. 18. Wildhaber JH, Dore ND, Wilson JM, Devadason SG, LeSouef PN. Inhalation therapy in asthma: nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children. J Pediatr 1999;135(1):28-33. 19. Coates AL, MacNeish CF, Lands LC. Factors influencing the rate of drug output during the course of wet nebulization. J Aerosol Med 1998;11:101-11. 20. Leung K, Louca E, Coates AL. Comparison of breath-enhanced to breath-actuated nebulizers for rate, consistency, and efficiency. Chest 2004;126(5):1619-27. 21. Wildhaber JH, Devadason SG, Hayden MJ, Eber E, Summers QA, LeSouef PN. Aerosol delivery to wheezy infants: a comparison between a nebulizer and two small volume spacers. Pediatr Pulmonol 1997;23(3):212-6. 22. Kerem E, Levison H, Schuh S, O'Brodovich H, Reisman J, Bentur L, et al. Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. J Pediatr 1993;123(2):313-7. 23. Tien I, Dorfman D, Kastner B, Bauchner H. Metered-dose inhaler: the emergency department orphan. Arch Pediatr Adolesc Med 2001;155(12):1335-9. 24. Osmond MH, Gazarian M, Henry RL, Clifford TJ, Tetzlaff J. Barriers to metered- dose inhaler/spacer use in Canadian pediatric emergency departments: a national survey. Acad Emerg Med 2007;14(11):1106-13. 25. Leversha AM, Campanella SG, Aickin RP, Asher MI. Costs and effectiveness of spacer versus nebulizer in young children with moderate and severe acute asthma. J Pediatr 2000;136(4):497-502. 26. Ploin D, Chapuis FR, Stamm D, Robert J, David L, Chatelain PG, et al. High- dose albuterol by metered-dose inhaler plus a spacer device versus nebulization in preschool children with recurrent wheezing: A double-blind, randomized equivalence trial. Pediatrics 2000;106(2 Pt 1):311-7. 27. Qureshi F, Pestian J, Davis P, Zaritsky A. Effect of nebulized ipratropium on the hospitalization rates of children with asthma. N Engl J Med 1998;339(15):1030-5. 28. Schuh S, Johnson DW, Callahan S, Canny G, Levison H. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma. J Pediatr 1995;126(4):639-45. 29. Scarfone RJ, Fuchs SM, Nager AL, Shane SA. Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics 1993;92(4):513-8. 30. Ratto D, Alfaro C, Sipsey J, Glovsky MM, Sharma OP. Are intravenous corticosteroids required in status asthmaticus? Jama 1988;260(4):527-9. 31. McFadden ER, Jr. Inhaled glucocorticoids and acute asthma: therapeutic breakthrough or nonspecific effect? Am J Respir Crit Care Med 1998;157(3 Pt 1):677-8. 32. Schimmer BP, Parker KL. Adrenocorticotropic hormone: adrenocortical steroids and their symthetic analogs, inhibition of the synthesis of actions of adrenocortical hormone. In: Hardman JG, editor. The pharmacological basis of therapeutics. New York: McGraw-Hill; 1996. p. 1459. 33. Schuh S, Reisman J, Alshehri M, Dupuis A, Corey M, Arseneault R, et al. A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma. N Engl J Med 2000;343(10):689-94. 34. 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Am J Respir Crit Care Med 1999;159:1029-30. 45. Travers A, Jones AP, Kelly K, Barker SJ, Camargo CA, Rowe BH. Intravenous beta2-agonists for acute asthma in the emergency department. Cochrane Database Syst Rev 2001(2):CD002988. 46. Keahey L, Bulloch B, Becker AB, Pollack CV, Jr., Clark S, Camargo CA, Jr. Initial oxygen saturation as a predictor of admission in children presenting to the emergency department with acute asthma. Ann Emerg Med 2002;40(3):300-7. 47. Qureshi F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. J Pediatr 2001;139(1):20-6. 48. Toogood JH, Baskerville J, Jennings B, Lefcoe NM, Johansson SA. Bioequivalent doses of budesonide and prednisone in moderate and severe asthma. J Allergy Clin Immunol 1989;84(5 Pt 1):688-700.

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First CJKMI(Oct., 1999, Suzhou, China) Beijing: Xue Yuan Publishing house © 1999. All right reservedProceedings of The F irst China-Japan-Korea Joint Symposium on Medical Informatics(CJKMI’99),1999,177-181 HCSL: a Human-Computer Commonly Understandable and Communicatable Medical Language Han-Fei Bao computer network center Shanghai University of Traditional Chinese Me

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