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Obtain a cardiopulmonary assessment on every patient with an acute asthma exacerbation on arrival to the ED. The choice and intensity of therapy depends on the severity of the exacerbation and the patient's response to initial treatment. Recommended doses for asthma therapies are summarized in Table 34-4. Consider applying oxygen in all ED patients with an acute exacerbation of their asthma. Hypoxia can lead to hypoventilation and acidosis, which can cause pulmonary vasoconstriction, pulmonary hypertension, and right heart failure. Check for signs of dehydration due to decreased intake or vomiting and provide intravenous (IV) fluids if needed. However, in acute asthma exacerbation, there may be increased secretion of antidiuretic hormone and increased capillary permeability, thus IV fluids should be used in moderation to avoid overhydration resulting in pulmonary edema. Antibiotics should be used only if evidence of concurrent infection exists. However, most exacerbations are secondary to viral upper respiratory infections (URIs) and hence antibiotics are rarely indicated.
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The aims of pediatric asthma treatment should be effective acute phase treatment, prevention of recurrent exacerbations, minimization of medication side effects, prevention of recurrent visits to the ED or hospitalizations, and optimization of long-term management. The use of a severity assessment clinical algorithm with an asthma care pathway can reduce hospital length of stay, reduce physician prescribing errors, and improve patient education, without a corresponding increase in treatment costs.13 Figure 34-1 provides an example of a treatment algorithm which can be used in an ED.
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β-Adrenergic Agonists
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Short-acting adrenergic bronchodilators are the first line of emergency treatment of asthma. Bronchodilation is produced by stimulation of β2-adrenoreceptors, which mediate an increase in cyclic AMP via the enzyme adenyl cyclase. Cyclic AMP stimulates binding of calcium ions to the cell membrane, reducing the mycoplasmal calcium concentration with resultant bronchodilation (smooth muscle relaxation), and stabilization of mast cells (Fig. 34-3). Stabilization of mast cells retards the release of histamine and other inflammatory products. β-adrenergic agonist, when given efficiently and in high doses, will quickly relieve acute bronchospasm without many side effects.14
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Albuterol (also known as salbutamol) is most commonly used in the United States. It is a short-acting β2-agonist (SABA). Aerosol therapy is most commonly used. It is as effective as IV or SC therapy and more effective than oral therapy.15 There are two main methods of delivering aerosolized medications. Numerous studies suggest comparable efficacy of metered dose inhalers (MDIs) and nebulization.16,17 MDIs are less expensive and more convenient, but require a cooperative child who understands the technique of administration. The concurrent use of an aero chamber or spacer will allow the younger children to use an MDI more effectively. For a child under 3 years of age, apply a mask to the mouthpiece of the spacer device to help administer the medications. The inhaler is actuated into the spacer device and the child inhales the medication immediately using five tidal breaths. Doses of 0.5 puffs/kg with a maximum of 10 to 12 puffs per dose are recommended for treatment of an acute exacerbation. The transition from general clinical use of jet nebulization to spacer/MDI in pediatric asthma has been categorized as slow but consistent, with concerns (unfounded) raised around cost, efficacy, and safety of spacer/MDI.18,19
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Particles generated by aerosolization vary in size. Only those in the 1 to 5 μm range are useful drug vehicles and are deposited in the lower airways. These represent only 10% of the output from an MDI, and 1% to 5% from jet nebulizer. The rest escape into the room, or are dissolved in mucous membranes and swallowed. Low flow rates and greater breath-holding periods optimize drug deposition in the lower airways. Oxygen flow rates of 6 to 7 L/min are recommended. Since so much of the drug escapes into the atmosphere, especially when being delivered to very young children, many physicians will administer “unit doses” (usually, 2.5 or 5 mg albuterol/3 mL NS) to all patients regardless of size. Larger nebulizer chambers allow for multiple drug unit doses (such as albuterol and ipratropium bromide) to be placed in the chamber and run over a period of time. This is less time-consuming for ED staff and avoids breaks in therapy in patients with moderate or severe exacerbations. Doses of 7.5 mg of albuterol mixed with 500 μg ipratropium for patients weighing less than 35 kg, and 15 mg albuterol with 1000 μg ipratropium in children weighing more than 35 kg can be mixed in the holding chamber and run over 1 hour. Continuous nebulization of albuterol, typically reserved for severe/critical asthma, at initial rates of greater than 3 mg/kg/h appears to be safe and effective.20 Continuous nebulization is usually started at approximately 0.5 mg/kg/h and titrated up or down as needed. The repeat assessments of the patient's clinical status and response should guide the frequency of aerosols and the rate of continuous nebulization.
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Other Adrenergic Agonists
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It has been hypothesized that IV bronchodilators may result in a more rapid clinical response due to the potentially higher systemic distribution of the medication.21 The role of IV adrenergic agonists, such as IV salbutamol, in addition to nebulized solutions remains unclear. They are currently recommended in international asthma treatment guidelines as second-line treatment in children who do not respond to regular inhaled β-agonist and corticosteroid therapy. A Cochrane review in 2001 concluded that there was little evidence to support IV use over any other regimens in the management of acute severe asthma.15 It further reported no significant clinical improvements whether given by continuous infusion or by bolus and also resulted in more clinical side effects. IV terbutaline (also a β2-selective agent) is safe and effective in both adult and pediatric patients with severe asthma exacerbations.22,23 However, more recently, a randomized double-blind placebo controlled trial recommended the physician exercise caution in its use and advised further trials to investigate its efficacy and safety.24
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Salmeterol is a long-acting β2-agonist (LABA) that has a longer duration of action but slower onset than albuterol. It is used primarily in the management of chronic moderately severe asthma to reduce the need for SABA. It is not intended for frequent repetitive administration or use in acute asthmatic exacerbation.
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Levalbuterol (Levosalbutamol or Xopenex) is the R-enantiomer of the SABA albuterol. It is promoted as an alternative to racemic albuterol to decrease the incidence of side effects. However, no studies have demonstrated such a benefit from this medication.25–27
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Inhaled epinephrine does not have any advantages over inhaled albuterol in acute asthma exacerbations.28 Epinephrine is also available as a SC injection. It is more toxic and no more effective than inhalation of a β2-selective drug. Parenteral administration (0.01 mL/kg up to 0.3 mL of the 1:1000 solution SC) should be reserved for those patients who are unable to generate adequate tidal volume to deliver aerosolized drug to the bronchial tree such as in severe asthma exacerbations. SC terbutaline (0.01 mg/kg up to 0.25 mg), which is more β2-specific, may be used as an alternative to SC epinephrine.
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Side effects associated with all β-adrenergic agonists are largely due to sympathomimetic effects and include tremors, anxiety, nausea, headache, vomiting, tachycardia, arrhythmia, hypertension, and hypotension. Non-sympathomimetic side effects include decreased oxygen saturation (secondary to altered V/Q matching), which is common, and paradoxical bronchospasm, which is rare. Metabolic side effects include hypokalemia, hypophosphatemia, hyperglycemia, and lactic acidosis. These side effects are often related to dose and route of administration and rarely require cessation of therapy. However, all patients receiving prolonged high-dose β-adrenergic therapy or IV adrenergic therapy should have their oxygen saturation, heart rate, blood pressure, and serum electrolytes monitored closely.
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Asthmatics have profound bronchoconstriction in response to cholinergic agonists; thus, anticholinergic agents play an important role in the treatment of asthma (Fig. 34-4). There has been a resurgence of interest in the use of anticholinergic agents due to better understanding of the cholinergic mechanisms that control airway caliber, and the development of synthetic analogs that are not appreciably absorbed across mucous membranes, minimizing side effects. Ipratropium bromide is a quaternary amine that fits into this category. It is a less potent bronchodilator, has a slower onset of action than the more commonly used β-adrenergic agonists, and is not recommended as first-line treatment in an acute exacerbation of asthma.29 Its use in combination with multiple dosing of β-agonists in pediatric patients is helpful in reducing rates of hospitalization.30 It is most efficacious when given as two to three doses in combination with the initial two to three albuterol treatments. This study included school-age children with asthma only. A 2005 review concluded that the indiscriminate use of anticholinergic agents was not advantageous in the treatment of wheezing children under the age of 2 years.31 Reported side effects of anticholinergic agents include dry mouth and a metallic taste.
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Multiple studies have demonstrated the effectiveness of corticosteroids in the treatment of asthma. Benefits include rate of improvement measured by clinical scores and pulmonary function studies, decreased duration of symptoms, decreased hospitalization rates, decreased relapse rates, and decreased need for β-agonists.32,33 A clearer understanding of the inflammatory mechanisms involved in the pathogenesis of even mild asthma has led to a greater emphasis on the use of steroids. Corticosteroids have multiple mechanisms of action in improving asthmatic patients. They restore responsiveness to β-adrenergics by increasing receptor numbers and lowering their threshold. Two mechanisms by which they reverse inflammation are inhibition of arachidonic acid metabolites via phospholipase and suppression of the polymorphonuclear response to chemotactic stimuli. Oral corticosteroids are preferred over parenteral corticosteroids in children as they are less invasive and equally efficacious.34 IV dosing is reserved for those patients who cannot tolerate oral medications, require continuous β-agonist therapy, or have impending respiratory failure. Following a short course of corticosteroid therapy, adrenal suppression is minimal and clinically insignificant. Toxicity is chiefly related to duration of use and not to dose. Therefore, doses at the top of the dose–response curve should be used and they should be stopped as soon as clinically allowable.
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Early administration of corticosteroids improves outcomes for asthma patients.35,36 A recent study showed that administration of systemic corticosteroids within 75 minutes of triage reduced admission rates and length of active treatment.37 Prednisone is the most commonly used corticosteroid; doses vary from 1 to 2 mg/kg/day for a duration of 3 to 5 days. Prednisone has a bitter taste and one of its most common side effects, whether taken in tablet or liquid form, is vomiting. There is some concern regarding the compliance of children and their caregivers in completing the 5-day course of prednisone. One study found that at least 7% of children seen in a pediatric ED never have their prescriptions filled.38 In another study, caregivers reported adherence to the prescribed length of oral corticosteroid therapy only 64% of the time.39 Investigators and clinicians have sought alternatives to this traditional therapy. Several clinical trials have examined the use of dexamethasone as an alternative.40–46 A dosage of 0.6 mg/kg of dexamethasone was used in two of these studies, giving a second dose on the following day.43,46 Three studies chose the intramuscular route for the administration of dexamethasone.42,44,45 Each of these seven studies found dexamethasone to be equally effective as a course of prednisone. One study further examined the cost-effectiveness of a dexamethasone versus prednisone regimen on relapse rates, representations, and hospital admissions and found a decreased rate of return visits to the ED, a reduction in subsequent hospitalizations, and significant cost savings in the dexamethasone group.47 The use of inhaled corticosteroids in the acutely ill asthmatic patient has been investigated but no significant benefit has been reported.48
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In patients who have not responded to the above therapy, one should consider administering magnesium sulfate. Magnesium produces bronchodilation via counteraction of calcium-mediated smooth muscle constriction. There is conflicting literature on its benefits for pediatric patients with an acute asthma exacerbation.49,50 A systematic review of the literature on IV magnesium for asthmatics of all ages did demonstrate a decrease in admission rate for those with severe acute asthma exacerbations.51 Doses of 25 to 75 mg/kg IV over 20 minutes are recommended for patients with a moderate or severe asthma exacerbation who do not respond to initial therapy with albuterol and ipratropium. More recently the MAGNETIC study, a double-blind randomized placebo controlled trial comparing the use of nebulized magnesium to nebulized placebo following standard acute asthma management, has shown a reduction in asthma severity scores in children. The greatest difference in scores was seen in children who had the shortest duration of exacerbation at time of presentation.52 A recent well-designed clinical Argentinian study examined the use of intravenous magnesium within the first hour of initiation of standard treatment in acute severe asthma.53 They found a significant reduction in the number of patients requiring ventilation compared with those managed with standard treatment and no IV magnesium. A further magnesium study in adults, the 3MG trial, a double-blind randomized controlled trial comparing nebulized and IV magnesium in acute severe asthma, showed no benefit from magnesium.54
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IV methylxanthines, for example, aminophylline, historically played an important role in the management of acute severe asthma. However, there is little consensus on their current use in the management of acute severe asthma.55 One randomized trial found aminophylline use to be of equivocal benefit when compared with IV β-adrenergic use.56 A Cochrane review in 2005 concluded that the addition of IV aminophylline to the routine treatment plan of β2-agonists and corticosteroids showed an improvement in lung function within 6 hours, but did not show a reduction in symptoms, in hospital length of stay, or nebulized treatments required.57 The review also concluded no role for methylxanthines in the management of mild-to-moderate asthma.
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Leukotriene Antagonists
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There is, as yet, no basis to recommend routine use of leukotriene antagonists in the ED management of asthma exacerbations. Early treatment with oral montelukast in the management of a mild asthma exacerbation, after ED care in a multi-center, randomized, placebo controlled study resulted in a reduction in asthma signs and symptoms and also a reduction in the need for further health care visits and in school absenteeism.58 Its utility has not yet been proven for moderate-to-severe acute asthma.59,60 Doses of 5 to 10 mg have been recommended depending on age of the child.
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Inhalation of a blend of helium and oxygen may be helpful for severe asthmatic patients unresponsive to other therapies. Current published literature is inconclusive as to its benefit and has not shown any significant complications with its use.61,62 New evidence suggests certain beneficial effects in patients with more severe obstruction. Since these conclusions are based upon between-group comparisons and small studies, they should be interpreted with caution.63
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Hypertonic saline nebulization use and its benefits are well described for the treatment of bronchiolitis and cystic fibrosis. Its use in the treatment of acute asthma is much newer. A recent randomized controlled double-blind study compared albuterol nebulization mixed with hypertonic saline (5%) with albuterol mixed with normal saline.64 It found that regular albuterol with hypertonic saline nebulization resulted in a shorter length of stay and a lower admission rate in preschool children.
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Intubation/Mechanical Ventilation
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Indications for intubation of an asthmatic patient include decreased level of consciousness, apnea, exhaustion, rising PaCO2 after treatment, PaO2 <60 mm Hg, and pH <7.2. An asthmatic may not immediately improve with intubation, since intubation does nothing to change lower airway obstruction. Intubation and mechanical ventilation may also put the patient at risk for serious complications. When intubating an asthmatic patient, the largest-diameter tube appropriate for the patient's size is used to avoid further increasing resistance. Although sedation is normally contraindicated in patients with asthma,5 sedation and paralysis may be indicated to avoid barotrauma secondary to the child struggling during passage of the endotracheal (ET) tube. A modified rapid sequence induction should be used. The dissociative anesthetic ketamine is known to have bronchodilatory properties and therefore is a good choice for a sedative. Paralysis with succinylcholine may increase secretions but is not contraindicated. Vecuronium or rocuronium are recommended by most authors, when muscle paralysis is indicated in a pediatric patient with a severe asthmatic exacerbation. Once intubated, patients will require sedation and paralysis to maintain effective ventilation. They also require a long expiratory time to avoid air trapping due to airway obstruction. Otherwise, the ventilator may be providing a second inspired breath before the first breath has been fully expired (stacking breaths). Intrinsic PEEP may cause an increase in intrathoracic pressure that leads to decreased venous return to the heart and can cause hypotension. Intubated asthmatic patients need to be watched carefully for the development of pneumothorax, or pneumomediastinum. Sudden changes in their respiratory or hemodynamic status may be due to a tension pneumothorax until proven otherwise. Ventilator settings should be adjusted to provide for adequate oxygenation with as low a peak pressure and PEEP as possible. The use of permissive hypercapnea (PCO2) levels (as high as 70–90 mm Hg) has been associated with decreased morbidity and mortality rates in intubated asthmatic patients.
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Challenges in Preschool Wheezers
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One area that continues to challenge emergency physicians is the treatment of preschool wheezers due to a number of factors including difficult clinical assessment, their inconsistent response to the usual asthma medications, and frequent intermittent wheeze secondary to a primary viral infection such as RSV or adenovirus. This leads to episodic wheezing with no inter-illness symptoms or signs. Bronchiolitis is the main diagnostic consideration for such presentations in this age group. There is now a body of evidence which supports the hypothesis that the pathophysiology underlying wheezing in the preschool population is different to that in atopic asthma in the school-age population.65,66
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The treating physician can give a trial of a bronchodilator in an infant under 2 years presenting with recurrent symptoms. If there is no response to the inhaled β-agonist treatment, then the differential diagnosis should be reviewed and other treatment measures considered. In infants, in whom a diagnosis of mild-to-moderate asthma is suspected, the use of inhaled β-agonist MDI medication with a spacer device is equally as effective, if not better, than nebulized formulations.67,68 Oral β-agonist treatment is not recommended in this age group as it does not affect symptom scores or length of stay when compared with placebo.69 No clinical benefit has been found for oral corticosteroids for episodic wheezing in preschool children,70,71 and oral corticosteroids should only be prescribed for critically ill preschoolers with wheezing.72