Acute asthma exacerbations in children: Outpatient management ] Dr. hala alrifaee

INTRODUCTION Clinical decision making in the management of the child with an acute asthma exacerbation includes the following questions How sick is the child? Which drugs should be used for treatment? What are the optimal doses and delivery routes? When is more aggressive management necessary

ASSESSMENT OF SEVERITY Clinical findings, occasionally supplemented by objective tests, should be used to assess the severity of an acute asthma exacerbation Clinical evaluation should be repeated frequently during the management of an acute asthma exacerbation to assess response to therapy

The history should include The time of onset of exacerbation Current medications and allergies Recent use of beta 2agonists

Risk factors for severe, uncontrolled disease, such as emergency department visits, hospital and intensive care unit admissions, repeated courses of oral glucocorticoids, and history of intubation, rapidly progressive episodes, or food allergy

The focused examination should include Vital signs and pulse oximetry Assessment of level of consciousness, anxiety, and agitation Assessment of breathlessness, wheezing, air entry, accessory muscle use, and retractions

Pulmonary index The Pulmonary Index Score (PIS) is an asthma score based on five clinical variables: respiratory rate, degree of wheezing, inspiratory to expiratory ratio, accessory muscle use, and oxygen saturation Each variable is assigned a score from 0 to 3 Total scores range from 0 to 15

As a general rule, a score of 7 to 11 indicates an exacerbation of moderate severity and a score of ≥12 indicates a severe attack. However, the PIS may underestimate the degree of illness in an older child; bradypnea, caused by a prolonged expiratory phase, will result in fewer points for the respiratory rate component

The PIS has been validated and used as an outcome measure in several clinical trials It can be used to assess initial severity, judge response to treatment, and facilitate admission and discharge planning

Peak flow rate A peak flow meter may be used to assess airflow obstruction, providing an objective assessment of disease severity. However, children younger than six years may not be able to cooperate with peak expiratory flow rate (PEFR) assessments and severely ill children may not be able to stand and provide three consecutive recordings, as is recommended. In addition, the reading is most helpful when the child's personal best PEFR measurement is known

Chest radiograph Chest radiographs (CXRs) rarely provide information that alters the management of children with acute asthma exacerbation Viral upper respiratory tract infections are the most common trigger for wheezing in children and the presence of low grade fever in children with acute asthma exacerbation often prompts clinicians to obtain chest radiographs to exclude pneumonia.

the rate of specific chest radiograph findings in this setting is extremely low, except in the presence of focal examination findings (eg, rales or decreased breath sounds), fever (>39ºC), or severe disease

Arterial blood gas — It is rarely necessary to obtain arterial blood gas (ABG) samples in children with acute asthma. Oxygen saturation can be assessed with pulse oximetry

severely ill children have hypercapnia on arrival to the emergency department (ED), but this usually improves after therapy. In children who require admission to the intensive care unit (ICU), measurement of PaCO2 via ABG after a clinical plateau has been reached provides an objective measure of disease severity. In moderately or severely ill children, ABG's obtained before aggressive intervention often are abnormal, but rarely affect management.

OVERVIEW OF TREATMENT The goals of therapy for acute severe asthma include Rapid reversal of airflow obstruction by repeated administration of inhaled bronchodilators and early institution of systemic glucocorticoids

Correction of hypoxemia and/or severe hypercapnia; hypoxemia is alleviated by administration of supplemental oxygen as necessary; hypercapnea usually improves with reversal of airflow obstruction. Reduction of likelihood of recurrence by intensifying baseline therapy

Supportive care Supportive care for children with acute asthma exacerbations includes administration of supplemental oxygen and fluids as necessary, and frequent monitoring of response to therapy.

Oxygen therapy — Nearly all patients with acute asthma have hypoxemia as a result of ventilationperfusion (V/Q) mismatch. Beta2 agonists may worsen this mismatch by causing pulmonary vasodilation in areas of the lung that are poorly ventilated. Humidified oxygen should be provided as needed to maintain an oxygen saturation of ≥92 percent

All nebulized medications should also be delivered with oxygen, generally at a flow rate of 6 to 8 L/min"

Monitoring The clinical status of children who are being treated for acute asthma should be monitored frequently. The frequency of monitoring varies depending upon the severity of illness and response to initial therapy, but for most patients is typically every 20 to 30 minutes for the first hour of therapy. Patients who require continuous nebulizer therapy continue to be monitored every 20 to 30 minutes.

Ongoing monitoring of respiratory and heart rates, oxygen saturation, degree of alertness, accessory muscle use, retractions, and PEFR (in children who are able to perform it) is crucial to decisions regarding disposition

The approach to the management of acute asthma exacerbations in the emergency department Initial treatment (beta 2agonist therapy and oral glucocorticoids) may be provided in the primary care setting

However, children with moderate to severe exacerbations require close observation for clinical deterioration, frequent treatments, and repeated evaluation. Thus, most children with moderate or severe asthma exacerbations should be managed in an emergency department setting

Inhaled shortacting beta 2agonists are the mainstay of emergent treatment of acute asthma exacerbations. For children with mild exacerbations, systemic glucocorticoids are usually added if the symptoms and signs of airway obstruction fail to resolve after the first treatment with inhaled beta 2agonists

Children with moderate or severe exacerbations should receive systemic glucocorticoids as soon as possible. Additional pharmacotherapeutic agents that may be indicated in children with moderate or severe asthma include nebulized ipratropium bromide, magnesium sulfate, and parenteral beta 2agonists,

Mild exacerbation For children with mild asthma exacerbation (PIS <7, we suggest the following Albuterol inhalation therapy administered via small volume nebulizer (SVN) at a dose of 0.15 mg/kg (maximum 5 mg) or metered dose inhaler (MDIS) at a dose of onequarter to onethird puff/kg (maximum eight puffs). If repeated doses are needed, they should be given every 20 to 30minutes for three doses

Moderate exacerbation For children with moderate asthma exacerbation (PIS 7 to 11, Administration of supplemental oxygen if oxygen saturation ≤92 percent in room air. Albuterol nebulization (0.15 mg/kg, maximum 5 mg) combined with ipratropium bromide (250 microgram/dose if 20 kg) every 20 to 30 minutes for three doses or continuously

Administration of systemic glucocorticoids soon after arrival in the emergency department or after the first inhalation therapy is initiated Administration of IV magnesium sulfate (75 mg/kg, maximum 2.5 g administered over 20 minutes) if there is clinical deterioration despite treatment with beta 2agonists, ipratropium bromide, and systemic glucocorticoids

Severe exacerbation For children with severe asthma exacerbation (PIS ≥12 Administration of supplemental oxygen if oxygen saturation is ≤92 percent in room air Albuterol nebulization (0.15 mg/kg, maximum 5 mg) combined with ipratropium bromide (250 microgram/dose if 20 kg), every 20 to 30 minutes for three doses or continuously.

Alternatively, epinephrine or terbutaline (0.01 mL/kg of a 1 mg/mL solution) with a maximum dose of 0.4 mg (0.4 mL) may be administered intramuscularly or subcutaneously for children with poor inspiratory flow or children who cannot cooperate with nebulized therapy

Patients who have received three doses of intermittent therapy and require additional albuterol therapy may be treated intermittently every 30 to 45 minutes or may be switched to continuous therapy.

Subsequent management depends upon response to initial therapy For patients with a poor response to initial treatment, we recommend Administration of IV methylprednisolone (1 to 2 mg/kg, maximum 125 mg Administration of IV magnesium sulfate (75 mg/kg, maximum 2.5 g administered over 20 minutes

For patients who do not respond to these interventions, administration of IV terbutaline may be indicated: bolus with 10 microgram/kg over ten minutes, then 0.3 to 0.5 microgram/kg per minute; infusion may beincreased by 0.5 microgram/kg per minute every 30 minutes to a maximum of 5 microgram/kg minute

PHARMACOTHERAPY Inhaled beta agonists — Inhaled shortacting beta 2agonists are the mainstay of emergent treatment of acute asthma exacerbations Albuterol is the most widely used shortacting beta 2agonist in the acute setting.

Inhaled beta 2agonists can be administered by intermittent nebulization, continuous nebulization, or metereddose inhaler with a spacer (MDIS). These delivery systems are discussed in detail separately

Nebulizer versus MDIS — When administering inhaled beta 2agonists intermittently, clinicians may use either small volume nebulizers (SVNs) or MDIS. These methods appear to be equally effective for children of all ages and with a wide range of illness severity. Advantages of SVN delivery compared to MDIS include the ability to simultaneously deliver humidified oxygen and ipratropium bromide and to passively administer drug therapy to a child in respiratory distress

Clinical trials and metaanalyses indicate that the administration of beta 2agonists via MDIS (4 to 12 puffs) is at least as effective, and possibly superior to delivery of medication by SVN in reversing bronchospasm in infants and children

Continuous delivery — Studies comparing continuous versus intermittent nebulized delivery of beta 2agonists have found similar outcomes and side effect profiles with both methods young children may not tolerate wearing a face mask for long periods of time.

When administering inhaled beta 2agonists, clinicians may begin with either intermittent or continuous administration. However, continuous therapy insures that the goal of three treatments within the first hour of care for moderately ill children is met. Therefore, we recommend continuous therapy over intermittently nebulized or MDIS therapy for children who require multiple treatments in the first hour or for an extended period

Intermittent albuterol nebulization — The standard dose for nebulized albuterol is 0.15 mg/kg (minimum 2.5 mg; maximum 5 mg Nebulized albuterol can be administered every 20 to 30 minutes for three doses

frequency of therapy may be limited by side effects, such as tachycardia, hypertension, or tremors. Patients who have shown little or no improvement after three doses and who are not experiencing significant adverse effects may be treated every 30 to 45 minutes or switched to continuous therapy.

Drug delivery is maximized by having a total solution volume of 3 to 4 mL and an oxygen flow rate of 6 to 8 L/min

Continuous albuterol nebulization — The optimal dose for continuous albuterol nebulization therapy has not been determined. One dosing schedule stratified by weight is: For children who weigh 5 to 10 kg, the dose is 10 mg/hr For children who weigh 10 to 20 kg, the dose is 15 mg/hr For children who weigh >20 kg, the dose is 20 mg/hr

The 2007 National Asthma Education and Prevention Program (NAEPP) guidelines state that "equivalent bronchodilation can be achieved either by high doses (4 to 12 puffs) of a shortacting beta agonist by MDS with a valved holding chamber or by nebulizer"; they suggest a dose of 4 to 8 puffs

To maximize drug delivery, a spacer should be employed by all patients and infants and young children should use a spacer with a face mask, low dead space, and a low resistance valve ( picture 1 ). Mouthpieces are preferable to face masks for older children to avoid nasal filtering of drug, which may reduce lung deposition

Glucocorticoids The antiinflammatory action of glucocorticoids effectively reduces the airway edema and secretions associated with acute asthma exacerbations

Systemic glucocorticoids are indicated for most children who present to the ED with acute asthma exacerbation. benefit of early administration (within one hour) of systemic glucocorticoids versus placebo in patients presenting to the ED with acute asthma exacerbation was evaluated in a metaanalysis of 12 trials involving 863 patients

Early administration of systemic glucocorticoids reduced admission rates Oral versus IV/IM — The NAEPP guidelines suggest that oral administration of glucocorticoids is preferred to intravenous administration because oral administration is less invasive and the effects are equivalent

Intramuscular administration of glucocorticoids may be warranted in patients who vomit orally administered glucocorticoids, yet do not require an intravenous line for other purposes

Children with acute asthma exacerbation who are critically ill usually require placement of an IV catheter for the administration of medications other than glucocorticoids. We suggest that children with acute asthma exacerbation who have an IV catheter, or are likely to need one placed because of critical illness, receive systemic glucocorticoids intravenously. We suggest that children with acute asthma exacerbation who do not require intravenous access for other reasons, receive systemic glucocorticoids orally. Oral dexamethasone phosphate is an alternative for children who vomit oral prednisone or prednisolone

Dose Oral prednisone. The initial dose of oral prednisone is 2 mg/kg (maximum 60 mg). In a controlled trial, 2 mg/kg of prednisone (maximum 60 mg) administered early in the course of ED care resulted in a significant reduction in the need for hospitalization among the sickest patients

Dexamethasone phosphate. Dexamethasone phosphate is another glucocorticoid that can be administered orally It has a longer halflife than prednisone (36 to 72 hours versus 18 to 36 hours The dose is 0.6 mg/kg (maximum dose 16 mg

Methylprednisolone. The usual does of intravenous methylprednisolone for acute asthma exacerbations is 1 to 2 mg/kg (maximum 60 mg

Inhaled glucocorticoids The use of inhaled glucocorticoids to treat children with acute asthma is an area of ongoing clinical research. Studies comparing the use of oral to inhaled glucocorticoids in the ED management of children with acute asthma have thus far had mixed results, as illustrated below:

Some studies have found benefits of inhaled glucocorticoids compared to oral glucocorticoids (eg, earlier discharge from the ED, less vomiting, decreased relapse rate, improved clinical parameters, improved pulmonary function

Other studies have found oral glucocorticoids and inhaled glucocorticoids to have similar outcomes

One study found improved pulmonary function and a lower relapse rate with oral prednisone compared to inhaled fluticasone One randomized trial found no additional benefit to adding nebulized budesonide to standard therapy (systemic glucocorticoids, and inhaled albuterol and ipratropium ) early in the course of treatment

Until more conclusive data are available, we do not suggest the routine use of inhaled glucocorticoids in addition to, or instead of, systemic glucocorticoids in the management of acute asthma exacerbation in children.

Ipratropium bromide Ipratropium bromide is an anticholinergic agent. provide bronchodilation through smooth muscle relaxation Ipratropium is indicated in the treatment of children with moderate to severe asthma exacerbations.

multiple doses of inhaled ipratropium combined with inhaled beta 2agonists have been shown to reduce hospital admissions and improve lung function in children with severe asthma exacerbations. In contrast, ipratropium has not been shown to reduce the length of hospital stay or to prevent admission to the ICU

A systematic review of 13 randomized trials comparing combined inhaled beta 2agonists and anticholinergic agents ( atropine sulfate and ipratropium bromide) with inhaled beta 2agonists alone found the following result

Single doses of combination therapy improved lung function 60 and 120 minutes after therapy, but did not reduce hospitalization Multiple doses of combined therapy reduced the risk of hospital admissionin children with moderate and severe exacerbations; Multiple doses of combined therapy also resulted in improved percent predicted FEV1

The use of combination therapy did not result in increased incidence of nausea, vomiting, or tremor compared to the use of beta 2agonists alone

We recommend that children with moderate to severe asthma exacerbations be treated with ipratropium bromide (250 microgram per dose for children who weigh <20 kg; 500 microgram per dose for children who weigh >20 kg

Magnesium sulfate There is accumulating evidence that intravenous magnesium sulfate benefits adults and children with severe asthma We suggest that magnesium sulfate be used in children with severe asthma exacerbations and in children with moderate asthma exacerbations who have clinical deterioration despite treatment with beta 2agonists, ipratropium bromide, and systemic glucocorticoids. We use a dose of 75 mg/kg (maximum 2.5 g) IV administered over 20 minutes

Parenteral beta 2agonists include epinephrine and terbutaline ; these drugs may be administered subcutaneously, intramuscularly, or intravenously

The rapid subcutaneous or intramuscular administration of beta 2agonists may be superior to inhaled beta 2agonists for children with severe exacerbations and poor inspiratory flow or anxious young children who are uncooperative with or have suboptimal response to initial aerosolized therapy

The dose of subcutaneous or intramuscular terbutaline for bronchodilation is 0.01 mg/kg per dose (0.01 mL/kg of a 1 mg/mL solution) with a maximum dose of 0.4 mg (0.4 mL); the dose may be repeated every 20 minutes for three doses

The dose of subcutaneous or intramuscular epinephrine for bronchodilation is 0.01 mg/kg (0.01 mL/kg of 1:1000 solution (1 mg/mL)), with a maximum dose of 0.4 mL (0.4 mg); the dose may be repeated every 20 minutes for three doses, then every two to six hours as needed

Intravenous — Severely ill patients who are poorly responsive to conventional therapy may be treated with a combination of intravenous (IV) beta 2agonists and inhaled beta 2agonists

Dosing for intravenous terbutaline in the emergency department setting is as follows: 10 microgram/kg bolus over 10 minutes, followed by 0.3 to 0.5 microgram/kg per minute; every 30 minutes the infusion may be increased by 0.5 microgram/kg per minute to a maximum of 3 microgram/kg per minute

There are insufficient data to support the routine administration of heliox, ketamine, or leukotriene receptor antagonists in the treatment of children with acute asthma

Heliox — A mixture of helium and oxygen theoretically may enhance beta 2agonist delivery because the lower gas density would result in decreased flow resistance

the patients were randomly assigned to receive continuous albuterol nebulization delivered by heliox or oxygen. At 240 minutes, patients in the heliox group had greater decrease in PIS score from baseline (decrease of 7 versus 3 points). In addition, more patients in the heliox group were discharged from the hospital in less than 12 hours (73 versus 33 percent).

Leukotriene receptor antagonists — The data do not support the routine use of leukotriene receptor antagonist (LTRA) therapy to treat children with acute asthma exacerbations requiring urgent or emergent care LTRA add on therapy in acute asthma has shown promise in adults [

Intravenous montelukast was effective in improving FEV1 in two randomized trials of adults with acute asthma but similar results were not seen in Children

Discharge to home Children who have marked improvement in clinical parameters within the first one to two hours of therapy may be discharged home Marked improvement is manifest by diminished or absent wheezing and retracting and increased aeration that is sustained at least 60 minutes after the most recent albuterol dose

Discharge meds guidelines state that discharged patients should be treated with beta 2agonists and oral systemic glucocorticoids for 3 to 10 days Whether inhaled glucocorticoids should be added to inhaled albuterol and oral glucocorticoids at the time of discharge from the ED for patients who are not already receiving glucocorticoids as controller therapy is a question that remains unanswered

Continued treatment and observation Children with some, but incomplete improvement within the first two hours of therapy require continued observation. Incomplete response is manifest by modest, but insufficient benefits in degree of wheezing, retracting, and aeration

During continued observation, patients with partial improvement should continue to receive albuterol nebulizations every 30 to 45 minutes (or continuously) for another one to two hours, after which a decision regarding hospitalization or discharge home is made

Hospitalization Patients who were moderately to severely ill on arrival and who have little improvement, and or continued need for supplemental oxygen after initial therapy with beta 2agonists and systemic glucocorticoids require hospitalization.

This includes patients who continue to have significant wheezing and retracting, poor aeration, or altered mental status, such as drowsiness or agitation.

Followup — Patients discharged from the ED should have followup in one to four weeks with their primary care provider

General approach The immediate goals of treatment of acute asthma exacerbation include rapid reversal of airflow obstruction and correction of severe hypercapnia or hypoxemia Inhaled shortacting beta 2agonists are the mainstay of management of acute asthma exacerbation. Systemic glucocorticoids are added if the signs and symptoms of airway obstruction fail to improve after the first treatment with inhaled beta 2agonists

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