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Home , Acute severe asthma

European Review for Medical and Pharmacological Sciences 2011; 15: 711-716 in children: treatment in emergency

P. PAVONE, M.R. LONGO, R. TAIBI, G. NUNNARI*, C. ROMANO, E. PASSANITI, R. FALSAPERLA

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: Introduction Asthma is one of the most common chronic dis- eases, leading to an increased rate of hospital- ization. Asthma is one of the most common chronic Material and Methods: The aim of this re- diseases, leading to an increased rate of hospital- port is to review the current concepts and treat- ization. Frequent respiratory infections, personal ment of asthmatic children, focusing our atten- or familial , disease severity and young tion on the treatment of children in a Department age are important factors leading to hospitaliza- of Pediatric Emergency. tion. However, regular clinical follow-up and use Discussion: Frequent respiratory infections, personal or familial allergy, disease severity and of inhaled , the IgE levels and O2 young age are important factors leading to hos- saturation may reduce the probability of hospital- pitalization. However, regular clinical follow-up ization during asthma attacks. The aim of this re- and use of inhaled corticosteroids, the IgE lev- port is to review the current concepts and treat- els and O2 saturation may reduce the probability ment of asthmatic children, focusing our atten- of hospitalization during asthma attacks. The di- tion on the treatment of children in a Department agnosis of asthma in children is based on rec- ognizing a characteristic pattern of episodic res- of Pediatric Emergency. piratory symptoms and signs, in the absence of A correct diagnosis of asthma is the first step an alternative explanation for them. The pres- toward attaining disease control. In general, a di- ence of these factors increases the probability agnosis of asthma is established if episodic that a child with respiratory symptoms will have symptoms of airflow obstruction or airway hy- asthma. These factors include age at presenta- per-responsiveness are present, airflow obstruc- tion; sex; severity and frequency of previous tion is at least partially reversible, and alternative wheezing episodes; coexistence of atopic dis- ease; family history of ; and abnormal lung diagnoses are excluded. The guidelines recom- function. mend the use of a detailed medical history, the Conclusion: Asthma is a chronic condition results of a physical examination (focusing on that often remains uncontrolled for reasons that the upper , chest, and skin), and may be related to the disease process itself, the the results of spirometry (for patients aged 5 management decisions of clinicians, the patien- years or older) in making the diagnosis. Particu- t’s perceptions of disease control or self-man- agement behaviors, the cost of medications, or larly important factors that should be addressed a combination of all of these factors. To this end, as part of the medical history include the fre- patients with asthma should be educated not to quency of symptoms (eg, perennial, seasonal, or accept a certain level of symptoms or activity both; continual, episodic, or both; diurnal varia- limitations as an inevitable consequence of tions), precipitating factors (such as the presence asthma. Both the levels of current impairment of allergic triggers), and a family history of asth- and the future risks (of asthma exacerbations or ma, allergy, or other atopic disorders. Although adverse medication effects) should be used to inform decisions about appropriate levels of recurrent and wheezing often result from asthma therapy, and physicians should be aware asthma, other causes of of the new medication recommendations. should be considered in the initial diagnosis, or if the patient does not respond to initial therapy. Key Words: Several other conditions may coexist, or compli- Asthma, Childhood, Emergency, Treatment. cate the diagnosis or management of asthma. The diagnosis of asthma is confirmed by a positive

Corresponding Author: Piero Pavone, MD; e-mail: [email protected] 711 P. Pavone, M.R. Longo, R. Taibi, G. Nunnari, C. Romano, E. Passaniti, R. Falsaperla response to asthma medication, and treatment Table II. Clinical features that lower the probability of asthma. should follow the usual stepwise approach to asthma management1-6,9,10. • Symptoms with colds only, with no interval symptoms The diagnosis of asthma in children is based • Isolated cough in the absence of wheezing or difficulty on recognizing a characteristic pattern of episod- breathing ic respiratory symptoms and signs (Table I) in • History of moist cough • Prominent dizziness, light-headedness, peripheral the absence of an alternative explanation for tingling them (Tables II and III). • No response to a trial of asthma therapy The presence of these factors increases the probability that a child with respiratory symp- toms will have asthma. These factors include age risk of adverse effects from medication”1-15. In as- at presentation; sex; severity and frequency of sessing impairment, asthma severity should be previous wheezing episodes; coexistence of evaluated using the following categories: atopic disease; family history of atopy; and ab- normal lung function. • Intermittent asthma severity Once the diagnosis has been established, the • Persistent asthma severity (mild, moderate, se- focus is on classifying to the severity of asthma vere). so that therapy can be initiated, and on monitor- ing control over time so that therapy can be ad- justed. According to the new guidelines, severity Clinical Assessment and control should be assessed separately, but both are classified on the basis of the domains of Before starting treatment for acute asthma in current impairment and future risk. Impairment is any setting, it is essential to assess accurately the defined as “the frequency and intensity of symp- severity of their symptoms. The following clini- toms and functional limitations the patient is ex- cal signs should be recorded: periencing currently or has recently experienced,” whereas risk is defined as “the likelihood of ei- • Pulse rate ther asthma exacerbations, progressive decline in • Respiratory rate and degree of breathlessness lung function (or, for children, lung growth), or • Use of accessory muscles of respiration • Amount of wheezing Table I. Clinical features that increase the probability of • Degree of agitation and conscious level asthma. Clinical signs do not always correlate with the More than one of the following symptoms: wheezing, severity of airways obstruction. Some children cough, difficulty breathing, chest tightness, particularly with do not appear dis- if these symptoms: tressed. • Are frequent and recurrent • Are worse at night and in the early morning • Occur in response to exercise or other triggers or Pulse oximetry: accurate measurements of oxy- emotions gen saturation are essential in the assessment • Occur apart from colds of all children with acute wheezing. Personal history of atopic disorder Family history of atopic disorder and/or asthma Consider intensive inpatient treatment for chil- History of improvement in symptoms or lung function dren with SpO2 <92% in air after initial bron- in response to adequate therapy chodilator 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 < 50-60 < 160 > 50-60 > 160 1-5 years < 40 < 120 > 40 > 120 > 50 > 140 > 6 years < 30 < 110 > 30 > 110 > 40 > 120

712 Acute asthma in children: treatment in emergency

PEF: a measurement of <50% predicted PEF or Doses can be repeated every 20-30 min. Con- β forced expiratory volume (FEV), with poor tinuous nebulised 2-agonists are of no greater improvement after initial treat- benefit than the use of frequent intermittent dos- ment is predictive of a more prolonged asthma es at the same total hourly dosage. If there is β attack. poor response to the initial dose of 2-agonists, Chest X-ray: A chest X-ray should be performed subsequent doses should be given in combination if there is subcutaneous emphysema, persisting with nebulised ipratropium bromide. unilateral signs suggesting , lobar collapse or consolidation and/or life threatening Ipratropium Bromide asthma not responding to treatment. There is good evidence for the safety and effi- Blood gases: Blood gas measurements should be cacy of frequent doses of ipratropium bromide β considered if there are threatening features not (every 20-30 min) used in addition to 2-agonists responding to treatment. Normal or raised for the first 2 hours of a severe asthma attack.

pCO2 levels are indicative of worsening asth- Benefits are more apparent in the most severe pa- ma. A more easily obtained free-flowing ve- tients. Frequent doses up to every 20-30 minutes

nous blood pCO2 measurement <45 mmHg ex- (250 μg/dose mixed with 5 mg of so- cludes . lution 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 Treatment of Acute Asthma in Children thereafter, according to the clinical response. The Aged Over 2 years ipratropium dose should be reduced to four to six hourly or discontinued. There is good evidence supporting recommen- dations for the initial treatment of acute asthma presenting to primary and secondary healthcare Steroid Therapy resources. There is less evidence to guide the use of second line therapies to treat the small number Steroid Tables of severe cases poorly responsive to first line The early use of steroids in Emergency De- measures. Despite this, the risk of death and oth- partments and assessment units reduce the need er adverse outcomes after admission to hospital for Hospital admission and prevent relapse in are extremely small irrespective of the treatment symptoms after initial presentation. Benefits can options chosen. be apparent within 3 or 4 hours. Children with severe or life threatening asth- Give prednisone early in the treatment of acute ma should be transferred to Hospital urgently1-20. asthma attacks. Use a dose of 1-2 mg/kg/day (max 40 mg/dose) 2 to 3 times. Betamethasone Oxygen 0.1-0.2 mg/kg/day (max 4 mg/dose), in 2 to 3 ad- Children with life threatening asthma or SpO2 ministrations. Intravenous administration of 1-2 <94% should receive high flow oxygen via a mg/kg/6-8 hours (max 40 mg dose). tight fitting face mask or nasal cannula at suffi- Oral and intravenous steroids are of similar ef- cient flow rates to achieve normal saturations. ficacy21. Intravenous hydrocortisone (5-10 mg/kg/6-8 h; 4 mg/kg repeated every 4 hours β Inhaled 2-Agonists should be reserved for severely affected children (Salbutamol/Terbutaline) who are unable to retain oral medication. β Inhaled 2-agonists are the first line treatment Treatment for up to 3 days is usually suffi- β for acute asthma. Children receiving a 2-agonist cient, but the length of course should be tailored via pressurized metered dose inhaled (pMDI) + to the number of days necessary to bring about spacer are less likely to have and hy- recovery. Weaning is unnecessary unless the poxia than the same drug given via a nebulizer. course of steroids exceeds 14 days. Children with severe or life threatening asth- Formulations such as hydrocortisone and ma (SpO2 <92%) should receive frequent doses methylprednisolone can be given parenterally. of nebulised driven by oxygen Studies have found these routes to be equally ef- (2.5-5 mg salbutamol or 5-10 mg terbutaline), al- fective, with the oral route being less painful and though children with mild symptoms can benefit invasive21,23. Prednisone is given for 5 days at a from lower doses. dose of 1 to 2 mg/kg daily (maximum 50

713 P. Pavone, M.R. Longo, R. Taibi, G. Nunnari, C. Romano, E. Passaniti, R. Falsaperla mg/dose). Dexamethasone can be given for 1 to ready receiving oral treatment and in those re- 5 days at a dose ranging from 0.3 to 0.6 mg/kg ceiving prolonged treatment. daily. Dexamethasone is a long-acting glucocor- Intravenous magnesium sulphate is a safe ticoid with a half-life of 36 to 72 hours, and is 6 treatment for acute asthma, but its place in times more potent than prednisone. Prednisone is management is not yet established. Doses of up shorter acting, with a half-life of 18 to 36 to 40 mg//kg/day (maximum 2 g) by slow infu- hours22. sion have been used. Studies of efficacy for se- In our practice in the Department of Pediatric vere childhood asthma unresponsive to more Emergency we are accustomed to seeing 18% to conventional therapies have been inconsistent. 20% of our patients with different degrees of Children can be discharged when stable on 3-4 asthmatic attack. After therapy almost 90-95% of hourly inhaled bronchodilators. This treatment them return home and 5% of the patients need can be continued at home. PEF and/or FEV hospitalization. should be >75% of best of predicted, and SpO2 >94%. Receptor Antagonists There is no clear evidence to support the use of leukotriene receptor antagonists for moderate Assessment of Acute Asthma in Children to severe acute asthma in the Emergency Depart- aged Less Than 2 Years ment. Leukotriene receptor antagonists is impor- tant as a chronic support therapy, but not in an The assessment of acute asthma in early child- acute attack. At the moment we do not have suf- hood can be difficult. Intermittent wheezing at- ficient data to determine if this drug could be tacks are usually due to viral infection and re- used during the acute follow-up phase with some sponse to asthma medication is inconsistent. Pre- dosing modifications. The use of these treat- maturity and low birth weight are risk factors for ments is beyond the scope of our review. recurrent wheezing. The differential diagnosis of symptoms includes aspiration , , , tracheomalacia, and Second Line Treatment of Acute Asthma complications of underlying conditions, such as in Children Aged Over 2 Years congenital anomalies and .

Children with continuing severe asthma de- β spite frequent nebulised 2-agonists and iprat- Treatment of Acute Asthma in Children ropium bromide plus oral steroids, and those Aged Less Than 2 Years with life threatening features, need urgent review β by a specialist with a view to transfer to a high 2-Agonist Bronchodilators β dependency unit or paediatric Intensive Care Inhaled 2-agonists are the initial treatment of Unit (ICU) to receive second line intravenous choice for acute asthma. Close fitting face masks therapies. There are three options to consider: are essential for optimal drug delivery. The dose salbutamol, and magnesium sul- received is increased if the child is breathing ap- phate. propriately, and not taking large gasps because of The early addition of a single bolus of intra- distress and screaming. venous salbutamol (5 μg/kg over 10 min) should There is good evidence that pMDI + spacer is be considered in severe cases where the patient as effective as, if not better than, nebulisers for has not responded to initial inhaled therapy. treating mild to moderate asthma in children Aminophylline is not recommended in chil- aged <2 years. β dren with mild to moderate acute asthma. Oral 2-agonists are not recommended for Aminophylline should be considered for children acute asthma in infants. with severe or life threatening bronchospasm un- responsive to maximal doses of bronchodilators Steroid Therapy plus steroids. Consider steroid tablets as early treatment of A 5 mg/kg loading dose should be given over severe episodes of acute asthma in the hospital 20 minutes with ECG monitoring, followed by a setting. Steroid tablet therapy (1-2 mg/kg of solu- continuous infusion at 1 mg/kg/hour. Serum ble prednisolone for up to 3 days) is the preferred theophylline should be measured in patients al- steroid preparation for use in this age group.

714 Acute asthma in children: treatment in emergency

ACUTE ASTHMA ATTACKS

Light Moderate Severe

Salbutamol spray Salbutamol spray Salbutamol spray (200 mcg) or via a (200-400 mcg) or via a (200-400 mcg) Incomplete nebulizer (0,1 mg/kg) in nebulizer (0.1 mg/kg) in 3 Over 20 minutes; plus response Worsening ipratropium bromide 3 administration or somministration or in case 250 mcg/dose in case of need of need; plus ipratropium every 20-30 min bromide 250 mcg/dose + every 20-30 min Prednisolone 1-2 mg/kg/die If there is a good response (max 40-50 mg/dose)

Incomplete response Good or incomplete response Good response Worsening Continue salbutamol Salbutamol spray (200-400 mcg) or via a nebulizer (0.1 mg/kg) in 3 somministrations or Resolution in case of need Hospitalization + Incomplete Prednisolone 1-2 mg/kg/day response or (max 40-50 mg/dose) worsening

Figure 1.

–––––––––––––––––––– Ipratropium Bromide Acknowledgements Inhaled ipratropium bromide should be con- β We are grateful to Prof. Lorenzo Pavone (Catania) for sidered in combination with inhaled 2-agonist for more severe symptoms. the helpful suggestions and the critical review of the manuscript. We also wish to thank International Sci- Many children with recurrent episodes of vi- ence Editing Co, Shannon Ireland, for editing the man- ral-induced wheezing in infancy do not go on to uscript. 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. References Parents of wheezy infants should receive ap- propriate discharge plans, along similar lines to 1) BRITISH THORACIC SOCIETY; SCOTTISH INTERCOLLEGIATE those given for older children. GUIDELINES NETWORK. British guidelines on the man- Figure 1 summarizes the therapy in an asthma agement of asthma. Thorax 2003; 58(Suppl 1): attack. The use of other new medicaments like S1-94. omalizumab monoclonal antibody seems to re- 2) KROEGEL C. Global initiative for asthma (GINA) guidelines: 15 years of application. Expert Rev duce the asthmatic attack in 50% of patients in Clin Immunol 2009; 5: 239-249. the first year with a good tolerability in children 6-11 years old, but is still controversial, and 3) NORTH OF ENGLAND EVIDENCE BASED GUIDELINES DEVEL- OPMENT PROJECT: SUMMARY VERSION OF EVIDENCE BASED more studies are needed to better clarify the safe- GUIDELINE FOR THE PRIMARY CARE MANAGEMENT IN ADULTS. ty of this therapy. The use of these treatments is North of England Asthma Guidelines Develop- beyond the scope of our review. ment Group. Br Med J 1996; 312: 762-766.

715 P. Pavone, M.R. Longo, R. Taibi, G. Nunnari, C. Romano, E. Passaniti, R. Falsaperla

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