Acute asthma in children: treatment in emergency

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1 European Review for Medical and Pharmacological Sciences Acute asthma in children: treatment in emergency P. PAVONE, M.R. LONGO, R. TAIBI, G. NUNNARI*, C. ROMANO, E. PASSANITI, R. FALSAPERLA 2011; 15: Department of Pediatrics and Pediatric Emergency, University Hospital Policlinico-Vittorio Emanuele, Catania (Italy) *Department of Infectious Diseases, University Hospital Garibaldi, Catania (Italy) Abstract. Background and Objective: Asthma is one of the most common chronic diseases, leading to an increased rate of hospitalization. Material and Methods: The aim of this report is to review the current concepts and treatment of asthmatic children, focusing our attention on the treatment of children in a Department of Pediatric Emergency. Discussion: Frequent respiratory infections, personal or familial allergy, disease severity and young age are important factors leading to hospitalization. However, regular clinical follow-up and use of inhaled corticosteroids, the IgE levels and O 2 saturation may reduce the probability of hospitalization during asthma attacks. The diagnosis of asthma in children is based on recognizing a characteristic pattern of episodic respiratory symptoms and signs, in the absence of an alternative explanation for them. The presence of these factors increases the probability that a child with respiratory symptoms will have asthma. These factors include age at presentation; sex; severity and frequency of previous wheezing episodes; coexistence of atopic disease; family history of atopy; and abnormal lung function. Conclusion: Asthma is a chronic condition that often remains uncontrolled for reasons that may be related to the disease process itself, the management decisions of clinicians, the patient s perceptions of disease control or self-management behaviors, the cost of medications, or a combination of all of these factors. To this end, patients with asthma should be educated not to accept a certain level of symptoms or activity limitations as an inevitable consequence of asthma. Both the levels of current impairment and the future risks (of asthma exacerbations or adverse medication effects) should be used to inform decisions about appropriate levels of asthma therapy, and physicians should be aware of the new medication recommendations. Key Words: Asthma, Childhood, Emergency, Treatment. Introduction Asthma is one of the most common chronic diseases, leading to an increased rate of hospitalization. Frequent respiratory infections, personal or familial allergy, disease severity and young age are important factors leading to hospitalization. However, regular clinical follow-up and use of inhaled corticosteroids, the IgE levels and O 2 saturation may reduce the probability of hospitalization during asthma attacks. The aim of this report is to review the current concepts and treatment of asthmatic children, focusing our attention on the treatment of children in a Department of Pediatric Emergency. A correct diagnosis of asthma is the first step toward attaining disease control. In general, a diagnosis of asthma is established if episodic symptoms of airflow obstruction or airway hyper-responsiveness are present, airflow obstruction is at least partially reversible, and alternative diagnoses are excluded. The guidelines recommend the use of a detailed medical history, the results of a physical examination (focusing on the upper respiratory tract, chest, and skin), and the results of spirometry (for patients aged 5 years or older) in making the diagnosis. Particularly important factors that should be addressed as part of the medical history include the frequency of symptoms (eg, perennial, seasonal, or both; continual, episodic, or both; diurnal variations), precipitating factors (such as the presence of allergic triggers), and a family history of asthma, allergy, or other atopic disorders. Although recurrent cough and wheezing often result from asthma, other causes of airway obstruction should be considered in the initial diagnosis, or if the patient does not respond to initial therapy. Several other conditions may coexist, or complicate the diagnosis or management of asthma. The diagnosis of asthma is confirmed by a positive Corresponding Author: Piero Pavone, MD; ppavone@unict.it 711

2 P. Pavone, M.R. Longo, R. Taibi, G. Nunnari, C. Romano, E. Passaniti, R. Falsaperla response to asthma medication, and treatment should follow the usual stepwise approach to asthma management 1-6,9,10. The diagnosis of asthma in children is based on recognizing a characteristic pattern of episodic respiratory symptoms and signs (Table I) in the absence of an alternative explanation for them (Tables II and III). The presence of these factors increases the probability that a child with respiratory symptoms will have asthma. These factors include age at presentation; sex; severity and frequency of previous wheezing episodes; coexistence of atopic disease; family history of atopy; and abnormal lung function. Once the diagnosis has been established, the focus is on classifying to the severity of asthma so that therapy can be initiated, and on monitoring control over time so that therapy can be adjusted. According to the new guidelines, severity and control should be assessed separately, but both are classified on the basis of the domains of current impairment and future risk. Impairment is defined as the frequency and intensity of symptoms and functional limitations the patient is experiencing currently or has recently experienced, whereas risk is defined as the likelihood of either asthma exacerbations, progressive decline in lung function (or, for children, lung growth), or Table I. Clinical features that increase the probability of asthma. More than one of the following symptoms: wheezing, cough, difficulty breathing, chest tightness, particularly if these symptoms: Are frequent and recurrent Are worse at night and in the early morning Occur in response to exercise or other triggers or emotions Occur apart from colds Personal history of atopic disorder Family history of atopic disorder and/or asthma History of improvement in symptoms or lung function in response to adequate therapy Table II. Clinical features that lower the probability of asthma. Symptoms with colds only, with no interval symptoms Isolated cough in the absence of wheezing or difficulty breathing History of moist cough Prominent dizziness, light-headedness, peripheral tingling No response to a trial of asthma therapy risk of adverse effects from medication In assessing impairment, asthma severity should be evaluated using the following categories: Intermittent asthma severity Persistent asthma severity (mild, moderate, severe). Clinical Assessment Before starting treatment for acute asthma in any setting, it is essential to assess accurately the severity of their symptoms. The following clinical signs should be recorded: Pulse rate Respiratory rate and degree of breathlessness Use of accessory muscles of respiration Amount of wheezing Degree of agitation and conscious level Clinical signs do not always correlate with the severity of airways obstruction. Some children with acute severe asthma do not appear distressed. Pulse oximetry: accurate measurements of oxygen saturation are essential in the assessment of all children with acute wheezing. Consider intensive inpatient treatment for children with SpO 2 <92% in air after initial bronchodilator treatment. Table III. Value of respiratory and cardiac rate in acute asthma. Light Moderate Severe AGE R.R. C.R. R.R. C.R. R.R. C.R. < 12 months < < 160 > > years < 40 < 120 > 40 > 120 > 50 > 140 > 6 years < 30 < 110 > 30 > 110 > 40 >

3 Acute asthma in children: treatment in emergency PEF: a measurement of <50% predicted PEF or forced expiratory volume (FEV), with poor improvement after initial bronchodilator treatment is predictive of a more prolonged asthma attack. Chest X-ray: A chest X-ray should be performed if there is subcutaneous emphysema, persisting unilateral signs suggesting pneumothorax, lobar collapse or consolidation and/or life threatening asthma not responding to treatment. Blood gases: Blood gas measurements should be considered if there are threatening features not responding to treatment. Normal or raised pco 2 levels are indicative of worsening asthma. A more easily obtained free-flowing venous blood pco 2 measurement <45 mmhg excludes hypercapnia. Treatment of Acute Asthma in Children Aged Over 2 years There is good evidence supporting recommendations for the initial treatment of acute asthma presenting to primary and secondary healthcare resources. There is less evidence to guide the use of second line therapies to treat the small number of severe cases poorly responsive to first line measures. Despite this, the risk of death and other adverse outcomes after admission to hospital are extremely small irrespective of the treatment options chosen. Children with severe or life threatening asthma should be transferred to Hospital urgently Oxygen Children with life threatening asthma or SpO 2 <94% should receive high flow oxygen via a tight fitting face mask or nasal cannula at sufficient flow rates to achieve normal saturations. Inhaled β 2 -Agonists (Salbutamol/Terbutaline) Inhaled β 2 -agonists are the first line treatment for acute asthma. Children receiving a β 2 -agonist via pressurized metered dose inhaled (pmdi) + spacer are less likely to have tachycardia and hypoxia than the same drug given via a nebulizer. Children with severe or life threatening asthma (SpO 2 <92%) should receive frequent doses of nebulised bronchodilators driven by oxygen (2.5-5 mg salbutamol or 5-10 mg terbutaline), although children with mild symptoms can benefit from lower doses. Doses can be repeated every min. Continuous nebulised β 2 -agonists are of no greater benefit than the use of frequent intermittent doses at the same total hourly dosage. If there is poor response to the initial dose of β 2 -agonists, subsequent doses should be given in combination with nebulised ipratropium bromide. Ipratropium Bromide There is good evidence for the safety and efficacy of frequent doses of ipratropium bromide (every min) used in addition to β 2 -agonists for the first 2 hours of a severe asthma attack. Benefits are more apparent in the most severe patients. Frequent doses up to every minutes (250 μg/dose mixed with 5 mg of salbutamol solution in the same nebulizer) should be used for the first few hours of admission. The salbutamol dose should be reduced to one to two hourly thereafter, according to the clinical response. The ipratropium dose should be reduced to four to six hourly or discontinued. Steroid Therapy Steroid Tables The early use of steroids in Emergency Departments and assessment units reduce the need for Hospital admission and prevent relapse in symptoms after initial presentation. Benefits can be apparent within 3 or 4 hours. Give prednisone early in the treatment of acute asthma attacks. Use a dose of 1-2 mg/kg/day (max 40 mg/dose) 2 to 3 times. Betamethasone mg/kg/day (max 4 mg/dose), in 2 to 3 administrations. Intravenous administration of 1-2 mg/kg/6-8 hours (max 40 mg dose). Oral and intravenous steroids are of similar efficacy 21. Intravenous hydrocortisone (5-10 mg/kg/6-8 h; 4 mg/kg repeated every 4 hours should be reserved for severely affected children who are unable to retain oral medication. Treatment for up to 3 days is usually sufficient, but the length of course should be tailored to the number of days necessary to bring about recovery. Weaning is unnecessary unless the course of steroids exceeds 14 days. Formulations such as hydrocortisone and methylprednisolone can be given parenterally. Studies have found these routes to be equally effective, with the oral route being less painful and invasive 21,23. Prednisone is given for 5 days at a dose of 1 to 2 mg/kg daily (maximum

4 P. Pavone, M.R. Longo, R. Taibi, G. Nunnari, C. Romano, E. Passaniti, R. Falsaperla mg/dose). Dexamethasone can be given for 1 to 5 days at a dose ranging from 0.3 to 0.6 mg/kg daily. Dexamethasone is a long-acting glucocorticoid with a half-life of 36 to 72 hours, and is 6 times more potent than prednisone. Prednisone is shorter acting, with a half-life of 18 to 36 hours 22. In our practice in the Department of Pediatric Emergency we are accustomed to seeing 18% to 20% of our patients with different degrees of asthmatic attack. After therapy almost 90-95% of them return home and 5% of the patients need hospitalization. Leukotriene Receptor Antagonists There is no clear evidence to support the use of leukotriene receptor antagonists for moderate to severe acute asthma in the Emergency Department. Leukotriene receptor antagonists is important as a chronic support therapy, but not in an acute attack. At the moment we do not have sufficient data to determine if this drug could be used during the acute follow-up phase with some dosing modifications. The use of these treatments is beyond the scope of our review. Second Line Treatment of Acute Asthma in Children Aged Over 2 Years Children with continuing severe asthma despite frequent nebulised β 2 -agonists and ipratropium bromide plus oral steroids, and those with life threatening features, need urgent review by a specialist with a view to transfer to a high dependency unit or paediatric Intensive Care Unit (ICU) to receive second line intravenous therapies. There are three options to consider: salbutamol, aminophylline and magnesium sulphate. The early addition of a single bolus of intravenous salbutamol (5 μg/kg over 10 min) should be considered in severe cases where the patient has not responded to initial inhaled therapy. Aminophylline is not recommended in children with mild to moderate acute asthma. Aminophylline should be considered for children with severe or life threatening bronchospasm unresponsive to maximal doses of bronchodilators plus steroids. A 5 mg/kg loading dose should be given over 20 minutes with ECG monitoring, followed by a continuous infusion at 1 mg/kg/hour. Serum theophylline should be measured in patients already receiving oral treatment and in those receiving prolonged treatment. Intravenous magnesium sulphate is a safe treatment for acute asthma, but its place in management is not yet established. Doses of up to 40 mg//kg/day (maximum 2 g) by slow infusion have been used. Studies of efficacy for severe childhood asthma unresponsive to more conventional therapies have been inconsistent. Children can be discharged when stable on 3-4 hourly inhaled bronchodilators. This treatment can be continued at home. PEF and/or FEV should be >75% of best of predicted, and SpO 2 >94%. Assessment of Acute Asthma in Children aged Less Than 2 Years The assessment of acute asthma in early childhood can be difficult. Intermittent wheezing attacks are usually due to viral infection and response to asthma medication is inconsistent. Prematurity and low birth weight are risk factors for recurrent wheezing. The differential diagnosis of symptoms includes aspiration pneumonitis, pneumonia, bronchiolitis, tracheomalacia, and complications of underlying conditions, such as congenital anomalies and cystic fibrosis. Treatment of Acute Asthma in Children Aged Less Than 2 Years β 2 -Agonist Bronchodilators Inhaled β 2 -agonists are the initial treatment of choice for acute asthma. Close fitting face masks are essential for optimal drug delivery. The dose received is increased if the child is breathing appropriately, and not taking large gasps because of distress and screaming. There is good evidence that pmdi + spacer is as effective as, if not better than, nebulisers for treating mild to moderate asthma in children aged <2 years. Oral β 2 -agonists are not recommended for acute asthma in infants. Steroid Therapy Consider steroid tablets as early treatment of severe episodes of acute asthma in the hospital setting. Steroid tablet therapy (1-2 mg/kg of soluble prednisolone for up to 3 days) is the preferred steroid preparation for use in this age group. 714

5 Acute asthma in children: treatment in emergency ACUTE ASTHMA ATTACKS Light Moderate Severe (200 mcg) or via a nebulizer (0,1 mg/kg) in 3 administration or in case of need If there is a good response Incomplete response ( mcg) or via a nebulizer (0.1 mg/kg) in 3 somministration or in case of need; plus ipratropium bromide 250 mcg/dose every min Worsening ( mcg) Over 20 minutes; plus ipratropium bromide 250 mcg/dose every min + Prednisolone 1-2 mg/kg/die (max mg/dose) Continue salbutamol Resolution Good response Incomplete response ( mcg) or via a nebulizer (0.1 mg/kg) in 3 somministrations or in case of need + Prednisolone 1-2 mg/kg/day (max mg/dose) Good or incomplete response Incomplete response or worsening Worsening Hospitalization Figure 1. Ipratropium Bromide Inhaled ipratropium bromide should be considered in combination with inhaled β 2 -agonist for more severe symptoms. Many children with recurrent episodes of viral-induced wheezing in infancy do not go on to have chronic atopic asthma. The majority do not require treatment with regular inhaled steroids. Parents should be advised about the relationship between cigarette smoke exposure and wheezy illnesses. Parents of wheezy infants should receive appropriate discharge plans, along similar lines to those given for older children. Figure 1 summarizes the therapy in an asthma attack. The use of other new medicaments like omalizumab monoclonal antibody seems to reduce the asthmatic attack in 50% of patients in the first year with a good tolerability in children 6-11 years old, but is still controversial, and more studies are needed to better clarify the safety of this therapy. The use of these treatments is beyond the scope of our review. Acknowledgements We are grateful to Prof. Lorenzo Pavone (Catania) for the helpful suggestions and the critical review of the manuscript. We also wish to thank International Science Editing Co, Shannon Ireland, for editing the manuscript. References 1) BRITISH THORACIC SOCIETY; SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK. British guidelines on the management of asthma. Thorax 2003; 58(Suppl 1): S ) KROEGEL C. Global initiative for asthma (GINA) guidelines: 15 years of application. Expert Rev Clin Immunol 2009; 5: ) NORTH OF ENGLAND EVIDENCE BASED GUIDELINES DEVEL- OPMENT PROJECT: SUMMARY VERSION OF EVIDENCE BASED GUIDELINE FOR THE PRIMARY CARE MANAGEMENT IN ADULTS. North of England Asthma Guidelines Development Group. Br Med J 1996; 312:

6 P. Pavone, M.R. Longo, R. Taibi, G. Nunnari, C. Romano, E. Passaniti, R. Falsaperla 4) CANE RS, RANGANATHAN SC, MCKENZIE SA. What do parents of wheezy children understand by wheeze? Arch Dis Child 2000; 82: ) DODGE R, MARTINEZ FD, CLINE MG. Early childhood respiratory symptoms and the subsequent diagnosis of asthma. J Allergy Clin Immun 1996; 98: ) MARTINEZ FD, WRIGHT AL, TAUSSIG LM, HOLBERG CJ, HALONEN M, MORGAN WJ. Asthma and wheezing in the first years of life. The group Health Medical Associates. N Engl J Med 1995; 322: ) CASTRO-RODRIGUEZ JA, HOLBERG CJ, WRIGHT AL, MAR- TINEZ AD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000; 162: ) SCHONBERGER H, VAN SCHAYCK O, MURIS J, BOR H, VAN DEN HOOGEN H, KNOTTNERUS A, VAN WEEL C. Towards improving the accuracy of diagnosing asthma in early childhood. Eur J Gen Pract 2004; 10: ) CHILDHOOD ASTHMA MANAGEMENT PROGRAM RESEARCH GROUP. The management of the childhood asthma. Grants for clinical trials. www. ClinicalTrials.gov. Accessed April 30, ) NATIONAL ASTHMA EDUCATION AND PREVENTION PRO- GRAM. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR-3). f Accessed March 30, ) CHAPMAN KR, BOULET LP, REA RM, FRANSSEN E. Suboptimal asthma control: prevalence, detection and consequences in general practice. Eur Respir J 2008; 31: ) RABE KF, ADACHI M, LAI CK, SORIANO JB, VERMEIRE PA, WEISS KB, WEISS ST. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol 2004; 114: ) STEMPEL DA, MCLAUGHIN TP, STANFORD RH, FUHLBRIGGE AL. Patterns of asthma control: a 3- year analysis of patient claims. J Allergy Clin Immunol 2005; 115: ) SAPRA SJ, BRODER MS, CHANG E. Alignement with the revised NHLBI 2007 asthma guidelines, Expert Panel Report 3 (EPR 3) in a large payer database. J Allergy Clin Immunol 2009; 123(Suppl 1): S ) HOLGATE ST, PRICE D, VALOVIRTA E. Asthma out of control? A structured review of recent patient surveys. BMC Pulm Med 2006; 6(Suppl 1): S2-S5. 16) HORNE R, PRICE D, CLELAND J, COSTA R, COVEY D, GRUFFYDD-JONES K, HAUGHNEY J, HENRICHSEN SH, KA- PLAN A, LANGHAMMER A, ØSTREM A, THOMAS M, VAN DER MOLEN T, VIRCHOW JC, WILLIAMS S. Can asthma control be improved by understanding the patient s perspective? BMC Pulm Med 2007; 7: 8. 17) BARNES PJ. The size of the problem of managing asthma. Respir Med 2004; 98(suppl 2): S4-S8. 18) OHAR JA, DONOHUE JF. Mono- and combination therapy of long-acting bronchodilators and inhaled corticosteroids in advanced COPD. Semin Respir Crit Care Med 2010; 31: ) US DEPARTMENT OF HEALTH AND HUMAN SERVICES, NA- TIONAL INSTITUTES OF HEALTH, NATIONAL HEART LUNG AND BLOOD INSTITUTE, NATIONAL ASTHMA EDUCATION AND PREVENTION PROGRAM. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No Bethesda, MD: US Dept of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; Accessed May 15, ) LONG AA. Addressing unmet needs in asthma care. P&T Digest 2005; 2: ) SHEFRIN AE, AND GOLDMAN RD. Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric patients. Can Fam Phys 2009; 55: ) BARNETT PL, CAPUTO GL, BASKIN M, KUPPERMAN N. Intravenous versus oral corticosteroids in the management of acute asthma in children. Ann Emerg Med 1997; 29: ) BECKER JM, ARORA A, SCARFONE RJ, SPECTOR ND, FONTANA-PENN ME, GRACELY E, JOFFE MD, GOLDSMITH DP, MALATACK JJ. Oral versus intravenous corticosteroids in children hospitalized with asthma. J Allergy Clin Immunol 1999; 103:

Asthma - Chronic. Presentations of asthma Cough Wheeze Breathlessness Chest tightness

Asthma - Chronic. Presentations of asthma Cough Wheeze Breathlessness Chest tightness Asthma - Chronic Definition of asthma Chronic inflammatory disease of the airways 3 components: o Reversible and variable airflow obstruction o Airway hyper-responsiveness to stimuli o Inflammation of