Management in the emergency department
The management of exacerbations of asthma requires rapid access to facilities or personnel capable of delivering bronchodilators appropriately, defining the severity of the asthma episode objectively, ensuring appropriate monitoring of oxygen delivery and instituting safe referral and disposition. Bronchodilators should be titrated using clinical and objective measurements, and systemic glucocorticosteroids should be given to almost all patients who must seek treatment in the emergency department. In addition to relief of symptoms and objective improvement in measures of airflow, a detailed review of risk factors for severe asthma is needed and an educational intervention offered or arranged.
Patient assessment (all ages)
The use of structured forms has been shown to improve documentation,[1, 2] and patient outcomes are improved when physicians are given a brief educational program on asthma guidelines with a poster summary.[3, 4]
Objective measurement of airflow (all patients more than 5 years of age)
Physicians' estimates of response to therapy are often inaccurate in acute asthma.5 Failure of initial bronchodilator therapy to significantly improve the FEV1 or PEF is predictive of a more prolonged attack course or the need for hospital admission.[6–11] The (SaO2) may correlate with PEF and, in some level III studies, correlates with the likelihood of admission.[12–19] Low (SaO2) may indicate a need for admission to hospital, but normal levels do not exclude severe asthma or the possibility of relapse. Measurement of (SaO2) may help to guide treatment in adult patients, but no studies have shown that arterial blood gases or (SaO2) predict outcome.
Drug therapy
Oxygen therapy will help normalize oxygen content while fixed airway obstruction related to airway inflammation and ventilation-perfusion mismatching resolve. This reduces the catecholamine response that can cause tachycardia and increased blood pressure.
Inhaled β2-agonists produce the most rapid relief from acute bronchospasm with the fewest side-effects.[20–22] Before treatment with inhaled β2-agonists (using a metered-dose inhaler [MDI] or wet nebulizer) does not preclude successful reversal of airflow limitation in the emergency department.23
Salbutamol is more effective and safer when inhaled than when taken intravenously.[20, 24–32] Intravenous use of bronchodilators should be considered only if the response to the inhaled drug is poor or if the patient is coughing excessively, is moribund or becomes so despite inhalation therapy.
The dosage of inhaled bronchodilators should be adjusted based on objective measures of airflow limitation and symptoms. It may be necessary to increase the dose to 1 puff every 30-60 seconds. There may not be a maximum dose, depending on the response to treatment, but some have suggested that 20-40 puffs may be required.[33, 34] Sometimes continuous wet nebulizer treatment is indicated. Relief of bronchospasm with inhaled bronchodilators is best achieved if the principle of cumulative dosing is followed: sequential doses build on the therapeutic effects of previously administered doses.[35–37] Prehospital treatment with inhaled β2-agonists (using an MDI or a wet nebulizer) does not preclude successful reversal of airflow obstruction in the emergency department.
Once a plateau is achieved (i.e., no further improvement noted after subsequent doses), continued administration of bronchodilators by any route is not likely to provide further clinical benefit and may result in toxic effects. Patients with severe asthma (i.e., FEV1 or PEF < 40% of previous best or predicted value), who fail to improve by clinical or objective assessment, require more frequent administration of bronchodilators and continuous monitoring. The plateau must be defined in relation to attack severity and improvement in terms of a combination of clinical and objective measures (≥15% improvement in FEV1 or PEF).
Three meta-analyses of level I studies in children38 and adults[39, 40] evaluating MDI and wet nebulization indicate that the use of an MDI with a chamber or spacer is associated with a more rapid onset of bronchodilation, shorter duration of emergency department treatment, fewer side-effects and greater patient preference.[38–41] More rapid and profound bronchodilation is achieved when sufficient doses are given with an MDI plus spacer device than when conventional doses are administered with a wet nebulizer.[42–44] This was true even in patients with the most severe airflow limitation (FEV1 < 0.67 L).42 The dry-powder inhaler (DPI) is at least as effective as an MDI or wet nebulization for acute asthma.[45, 46]
In 2 meta-analyses of placebo-controlled trials,[47, 48] glucocorticosteroids resulted in more rapid resolution of airflow limitation in admitted patients49 and decreased relapse rate among those discharged from the emergency department. Systemic glucocorticosteroids should be given as soon as possible in all patients with moderate or severe asthma (i.e., FEV1 or PEF < 60% of predicted value).
For patients in the emergency department or hospital, intravenous glucocorticosteroid therapy has no advantage over oral therapy in terms of rate of resolving airflow limitation.47 The parenteral route is preferred if patients are unable to take medication orally (e.g., they are too breathless or are intubated) or if they are unable to absorb an oral dose readily (e.g., because of vomiting). The recommended oral dose is 40-60 mg of prednisone47 or equivalent and the single intravenous dose is 125 mg solumedrol or 200 mg hydrocortisone.[50, 51]
In 4 meta-analyses[52–55] of double-blind studies of therapy for acute asthma in adults and children, the combination of ipratropium bromide with a β2-agonist was superior to a β2-agonist alone in improving lung function. This combination was especially beneficial to patients with the most severe airflow limitation (i.e., FEV1 < 1 L or PEF < 140 L/min): the mean increase in FEV1 was 55.6% with the combination therapy, compared with 38.9% using a β2-agonist alone.[56–61] In one study,56 the combination of ipratropium bromide plus nebulized salbutamol not only produced greater bronchodilation but was also associated with fewer adverse effects (e.g., tachycardia and tremor) than larger doses of β2-agonists alone. At least 4 level I studies[62–65] have reported no clinical benefit from adding anticholinergics. A systematic review of the use of anticholinergics in children[54, 55] and a recent level I study66 showed clear evidence of improvement in lung function and a 30% reduction in hospital admission rates in children with severe asthma. Studies of the treatment of mild to moderate asthma with single doses of ipratropium bromide have not shown any clinical benefit,67 but lung function improvements in moderate asthma may warrant the use of this drug, particularly if it reduces both the need for frequent β2-agonists and some of the related side-effects.
A meta-analysis of 13 level I studies of the use of aminophylline concluded that it does not provide a significant, additive bronchodilator effect compared with adequate doses of inhaled β2-agonists in cases of acute asthma and appears to be associated with an increased risk of adverse effects.68
Management of refractory cases
Three randomized controlled trials[69–71] and a systematic review72 showed additional benefit when magnesium was given to patients with severe asthma exacerbations who had not responded to standard β-agonist therapy. Two level I studies[73, 74] that found no such benefit did not limit treatment to unresponsive cases. The safety of magnesium and the potential benefit justify its use in people with severe asthma who fail to respond to titrated bronchodilators and glucocorticosteroids.
Parenteral bronchodilator therapy may be indicated when the inhaled route is not practical: for example, in patients who are coughing excessively, are too weak to inspire adequately or are moribund.
Intubated patients with asthma who do not respond to conventional bronchodilator therapy may benefit from an inhaled anesthetic agent with bronchodilating properties, such as ether,75 halothane,[76–78] enflurane79 or isoflurane.[80, 81] Hypotension and cardiac dysrhythmias are associated with the use of these agents and are more likely to occur in hypoxemic patients.
The mode of ventilation for status asthmaticus may be a crucial factor in a successful outcome.[82–85] It is often difficult or nearly impossible to use ventilation because of the extreme hyperinflation associated with severe restrictive and obstructive defects. Ventilation strategies emphasize caution in attempts to reduce the partial pressure of carbon dioxide abruptly to normal levels.[83–85] It is advisable to use a controlled mechanical hypoventilation approach that accepts moderate to high degrees of hypercarbia until lung function improves, with occasional intravenous administration of bicarbonate to keep pH above 7.2.[83–85] The risk of barotrauma and volutrauma (shock) can be minimized with slow machine rates (6-8 breaths/min) allowing a low inspiration-to-expiration ratio and with low tidal volumes (6-8 mL/kg). With ventilation, patients may also require frequent suctioning of mucous secretions that are often seen in life-threatening attacks.
The efficacy of heliox has not been confirmed in a randomized controlled trial.[86, 87] Benefit was reported in an observational study86 and some believe that it has a role in refractory asthma.87
Ketamine is recommended as the agent of choice for intubation using a modified rapid-sequence intubation technique. It has a rapid response time, provides good levels of anesthesia and is a good bronchodilator (level IV evidence).[88–90] Pretreatment with benzodiazepines helps prevent the occasional reactions (hallucinogenic episodes) associated with ketamine.91
Immediately after administration of the sedative(s) (ketamine, benzodiazepine), paralysis should be induced with succinylcholine because it has the fastest response time and the shortest duration of action of drugs in its class. Paralysis following intubation should be maintained using vecuronium (0.15 mg/kg intravenously). Bag-and-mask ventilation does not precede intubation in a rapid-sequence intubation technique. It is difficult or even impossible to use bag-and-mask ventilation in cases of acute asthma because of severe hyperinflation. It may also cause harm by provoking gastric distension and an increased risk of aspiration. If there is a failure to successfully intubate, bag-and-valve-mask ventilation should be initiated while preparing for other airway interventions.
In children, pretreatment with atropine is recommended to prevent bradycardia that may occur with the use of succinylcholine.
Discharge treatment plan and follow-up care
Spirometry and clinical assessment are used to establish risk of relapse. Important risk factors include admission to hospital or a visit to the emergency department in the previous 12 months, recent use of glucocorticosteroids, use of multiple categories of asthma medication, a previous severe or life-threatening asthma attack and the presence of psychosocial problems.[92–97] The most compelling evidence for using oral glucocorticosteroids comes from a Cochrane Collaboration review48 showing that the pooled odds ratio for treatment with oral glucocorticosteroids after discharge is 0.35 (95% CI 0.17-0.78) or a 65% reduction in relapses. Tapering doses of oral glucocorticosteroid has been popular in the past, but there is level I evidence that this is not necessary when duration of use is 15 days or less.[47, 48, 98] The recommended dose of inhaled glucocorticosteroid (beclomethasone or budesonide) at the time of discharge is 500-1000 μg/d, but this may depend on the dose and duration of oral glucocorticosteroid therapy (level IV). The more indicators of risk of asthma-related death or readmission to hospital in the patient's history the higher the recommended dose of inhaled glucocorticosteroids.[94, 96, 99]
Expert opinion indicates that high-dose inhaled glucocorticosteroid alone at discharge may be a reasonable choice in some cases after an asthma exacerbation. However, until further prospective trials confirm these findings, the use of oral and inhaled glucocorticosteroid at discharge is recommended.
Most experts believe that educating patients about asthma is the key to optimum disease control.[92, 100–104] Whenever possible, emergency staff should develop brief written treatment plans with clear instructions for follow-up care and a review of drug-delivery techniques.
Management of acute asthma in hospital
Response to emergency treatment, clinical features that reflect the current attack and past disease severity, socioeconomic risk factors and pulmonary function tests are all used to determine the need for admission to hospital. Normally, patients over 5 years of age who achieve 60%-70% of predicted or previous best lung function (based on measures of PEF or FEV1) will not require admission to hospital unless clinical factors indicating risk of relapse are significant. Important factors that define a patient at high risk for relapse include admission to hospital or a visit to the emergency department in the previous 12 months, recent use of systemic glucocorticosteroids, use of multiple categories of asthma medication, previous severe or life-threatening asthma attack, presence of psychosocial problems and the frequent, regular use of inhaled β2-agonists.
The principles of inpatient management incorporate the spectrum of treatment options that are used in both acute and long-term phases of asthma management. Opportunities exist to evaluate the need for education and to review barriers to compliance with treatment plans.
Systemic glucocorticoids are effective in reducing the duration and severity of asthma exacerbations.[47, 48] Administration of glucocorticosteroids orally is preferred over the intravenous route, except when the patient is unable to absorb the medication due to dehydration or vomiting or in severely unresponsive patients who are critically ill. The question of administering inhaled glucocorticoids to patients in hospital has not been specifically addressed in a randomized controlled trial. As they are the mainstay of treatment in moderate and severe asthma, expert opinion indicates that early initiation of treatment or continuation of prescribed inhaled glucocorticoids reinforces the importance of the treatment.
Rapid onset of action, ability to titrate, reduced cost, more effective use of hospital staff and better side-effect profile all make MDIs or DPIs preferable to wet nebulization in all age groups.[105–107] The MDI with a spacer has been shown to be at least as effective or superior to wet nebulization in all age groups at all levels of severity, and the device is associated with fewer side-effects and greater patient acceptance.[38, 41, 108] Attempts to establish optimum level and frequency of dose in acute asthma have failed to reveal any clearly superior schedule of drug therapy.[40, 42, 109] Continuous or higher doses on a fixed schedule are associated with more side-effects110 without clear superiority in terms of clinical outcome or pulmonary function. Following maximum bronchodilation, the schedule of therapy should be based on a combination of serial measurement of PEF, and any worsening of symptoms. Symptom-based treatment alone can lead to overuse of β-agonists. This can be prevented by confirming the association between PEF or FEV1 and the patient's perception of the need for treatment.
Inpatient management with an MDI or DPI allows for dose titration, reinforcement of drug delivery technique, greater involvement of the patient in self-management and lower fixed and variable cost to hospitals.105
Respiratory therapy time is more efficiently spent carrying out objective measurements and educating patients than simply administering wet nebulization treatments.
Over the last 10 years, every published guideline on asthma management[33, 34, 101–103, 111, 112] has recommended the use of spirometry for accurate diagnosis and to aid in admission or discharge decisions, as both the perception of patients and physician assessment of airway obstruction have been shown to be poorly correlated with lung function.[113, 114]
Unrecognized, persistently poor lung function can lead to unsafe treatment choices or inappropriate discharge plans. Continued treatment with high, fixed doses of bronchodilators after maximum bronchodilation or a return to normal lung function is an inefficient use of hospital staff and is likely to cause unnecessary side-effects. Titration of any medication is best achieved through serial objective measurements until the endpoint is reached. Relying on symptoms alone increases the risk of under- or over-treatment.
Increased pressure on Canadian facilities to use inpatient beds efficiently has led to the early discharge of patients with many types of problems. Patients with asthma should be discharged only if a safe level of relapse risk has been established using such objective criteria as pulmonary function tests.
In patients with severe asthma, PEF should be measured at any sign of deterioration and before and after administration of bronchodilators until their condition is stable. All patients admitted to hospital due to acute asthma should have daily pulmonary function tests to help establish parameters for safe discharge and drug doses.
The inability to predict rapid deterioration in acute asthma is described in case-control series for fatal and near-fatal asthma. Controlled trials to evaluate the question of management of patients on the hospital ward versus the intensive care unit are neither ethical nor necessary.
Intubated asthmatic patients clearly require admission to an intensive care unit for appropriate management. Controlled hypoventilation or permissive hypercapnia is recommended to avoid barotrauma in the intubated patient with asthma[83–85] Inhaled anesthetics,[75–81] ketamine,[88–90] magnesium sulfate,[69–72, 115] intravenous β2-agonists,116 aminophylline[117, 118] and heliox86 are all considerations in the ventilated or severely unresponsive or deteriorating patient with asthma. Prospective blinded and unblinded trials have all confirmed some improvement in airway pressure or indices of oxygen delivery for all these agents. Consultation with a critical care or asthma specialist is strongly advised when using these types of agents, particularly if the patient is not responding.
The primary indicators of inadequate response to treatment are a persistent requirement for oxygen to maintain SaO2 > 94%, the need for frequent doses of titrated bronchodilators to control symptoms or a PEF of 40% or less of predicted value despite adequate doses of inhaled bronchodilators.
The monitoring of arterial blood gases is the most accurate way to confirm oxygen content, ventilatory insufficiency and metabolic derangements associated with inadequate oxygen delivery. The decision to intubate is based primarily on clinical status, but deterioration of arterial blood gases or failure to improve may provide another indicator of risk of deterioration or the need for management in the intensive care unit.
Initiation of asthma education should occur during the stay in hospital. Reduced admission rates, and less school and work absenteeism are expected benefits.[119–121]
Presumably, the patient with severe persistent asthma or frequent severe attacks has failed to improve due to lack of compliance with treatment, poor understanding of the condition or a brittle disease pattern. It has been suggested that asthma outcome may be better in patients seen by specialists.122 Studies of the effectiveness of asthma education indicate that it increases patient satisfaction and reduces the need for admission to hospital and emergency department visits, especially in patients with severe asthma or those who have frequent treatment failures.[119, 123] Because education programs are usually organized and monitored by asthma specialists, it follows that their involvement in the follow-up of severe asthma is recommended.
The criteria for safe discharge from hospital are essentially the same as those for discharge from the emergency department. The main differences may relate to the fact that some people with asthma are admitted to hospital due to clinical risk factors or socioeconomic circumstances, rather than pulmonary function criteria.[33, 96, 97, 123, 124] The need to establish a clear action plan and ensure delivery of appropriate drug therapy is important for all patients with asthma, but patients in hospital are a particularly important group if admission is part of an ongoing pattern of poor disease control.125
Recommendations
• A structured management plan should be used to treat patients with asthma in the emergency department (level III).
• The severity of airflow limitation should be determined objectively using spirometry (the preferred method), PEF measures or both, before and after bronchodilator therapy (level III), unless the patient is too young (< 6 years), uncooperative or moribund. These measurements should not postpone necessary treatment (level IV).
• The arterial oxygen saturation (SaO2) should be measured before and after treatment (level III).
Recommendations
• Supplemental oxygen should be used in treating patients with acute asthma to maintain (SaO2) > 94% (level IV).
• Short-acting β2-agonists should be considered the primary class of medication for the management of exacerbations. It should be administered by inhalation and titrated using objective and clinical measures of airflow obstruction as guides (level I).
• The choice of delivery device (MDI with spacer, wet nebulization, dry-powder inhaler) will depend on the need for expedient treatment, availability of staff and the individual patient of any age (level I).
• The use of an MDI with a chamber (valved spacer device) is preferred over the use of a wet nebulizer for patients of all ages at all levels of severity (level I).
• All patients treated in the emergency department for an acute episode of asthma should be considered candidates for systemic glucocorticosteroid therapy (oral or intravenous) and receive it as soon as possible (level I).
• An anticholinergic drug should be added to β2-agonist therapy for severe acute asthma and β-blocker-induced bronchospasm and may also help in cases of moderate acute asthma (level I).
• Aminophylline is not usually recommended for use as a bronchodilator in patients of any age during the first 4 hours of asthma management in the emergency department (level I).
Recommendations
• Epinephrine (intramuscular or intravenous), salbutamol (intravenous) and inhaled anesthetics are recommended as alternatives to conventional therapy in unresponsive cases of life-threatening asthma (level II).
• Intravenous magnesium sulfate (level I) and heliox (level III) may be useful in addition to usual therapy for refractory asthma.
• Ketamine and succinylcholine are recommended for rapid-sequence intubation in cases of life-threatening asthma (level I).
• Intubation should be performed by physicians experienced with this procedure (level IV).
Recommendations
• Consideration for discharge should be based on results of spirometry (percent of previous best, or percent of predicted or absolute value) and assessment of clinical risk factors for relapse (level III).
♦ Patients with a pretreatment FEV1 or PEF below 25% of previous best level or the predicted value (i.e., FEV1 < 1.0 L or PEF < 100 L/min) usually require admission to hospital.
♦ Patients with a post-treatment FEV1 or PEF below 40% of previous best level or the predicted value (i.e., FEV1 < 1.6 L or PEF < 200 L/min) usually require admission to hospital.
♦ Patients with a post-treatment FEV1 or PEF between 40% and 60% of previous best level or predicted value (i.e., FEV1 = 1.6-2.1 L or PEF = 200-300 L/min) are possible candidates for discharge.
♦ Patients with a post-treatment FEV1 or PEF above 60% of previous best level or predicted value (i.e., FEV1 > 2.1 L or PEF > 300 L/min) are likely candidates for discharge.
• Adults discharged from the emergency department who require glucocorticosteroid therapy should be given 30-60 mg/d of prednisone orally (or equivalent) for 7-14 days. No tapering is required over this period (level I). Children should receive 1-2 mg/kg a day of prednisone or equivalent (up to a maximum of 50 mg) for 3-5 days (level I).
• Inhaled glucocorticosteroids are an integral component of asthma therapy and should be prescribed for almost all patients at discharge, including those receiving oral glucocorticosteroids (level I).
• A treatment plan and clear instructions for follow-up should be given to patients discharged from the emergency department. Patients with high-risk factors, poor lung function or indications of chronic poor control should be referred to an asthma education clinic (level IV).
Recommendations
• All patients admitted to hospital for acute asthma should be given systemic glucocorticosteroids, preferably by the oral route (level I).
• All patients should receive inhaled glucocorticosteroids in addition to systemic glucocorticoids (level IV).
• Bronchodilators should be administered by the inhaled route and their need should be determined using objective measurements. The choice of delivery device (MDI with spacer, wet nebulization, DPI) will depend on the need for expedient treatment, the availability of staff and patient selection (level I). Rapid onset, the possibility of titration, reduced cost, more effective use of hospital staff, better side-effect profile and increased opportunities for education all make MDIs or DPIs preferable to nebulization in all age groups (level I).
• Inhaled anticholinergics should be added to β2-agonist therapy for 24-48 hours in cases of severe asthma and possibly moderate asthma (level I).
• Response to treatment and criteria for discharge should be based on serial pulmonary function studies and control of symptoms (level III).
• Patients with severe airflow obstruction (FEV1 or PEF < 40% of previous best or predicted value following emergency treatment) or those who are hypercapnic, are unresponsive to treatment, deteriorating or have been intubated must have continuous care in the emergency department or a unit capable of frequent or continuous monitoring of oxygenation until their condition is stable or improved (level IV).
• Supplemental oxygen guided by oximetry to achieve SaO2 > 94% is recommended (level IV).
• Serial administration of arterial blood gases is recommended for critically ill patients and those with severe asthma if SaO2 is persistently low (< 90%) or if there is suspicion of hypercapnia (level IV).
• Patient education, including a formal written action plan for treatment after discharge, should occur during the hospital stay (level I).
• After discharge, patients should continue systemic glucocorticosteroids (30-60 mg/d for adults and 1-2 mg/kg daily for children) for at least 3-5 days for children and 7-10 days for adults (level I).
• Patients should continue to take inhaled glucocorticosteroids after discharge with adjustment of the dose according to the action plan or on the advice of a physician at a follow-up visit (level I).
• Follow-up arrangements with the primary care physician or asthma specialist must be made before discharge (level IV).
• Patients with severe disease (FEV1 or PEF < 40% of previous best or predicted post-treatment value and/or frequent attacks) should be seen by a specialist during the hospital stay or as a follow-up after discharge (level IV).
• Patients who have achieved more than 70% of predicted or previous best pulmonary function, who have access to the required medication, whose inhaled drug delivery technique is confirmed to be adequate and who have a written action plan can be discharged from hospital (level IV).
References
- 1.↵
- 2.↵
- 3.↵
- 4.↵
- 5.↵
- 6.↵
- 7.
- 8.
- 9.
- 10.
- 11.↵
- 12.↵
- 13.
- 14.
- 15.
- 16.
- 17.
- 18.
- 19.↵
- 20.↵
- 21.
- 22.↵
- 23.↵
- 24.↵
- 25.
- 26.
- 27.
- 28.
- 29.
- 30.
- 31.
- 32.↵
- 33.↵
- 34.↵
- 35.↵
- 36.
- 37.↵
- 38.↵
- 39.↵
- 40.↵
- 41.↵
- 42.↵
- 43.
- 44.↵
- 45.↵
- 46.↵
- 47.↵
- 48.↵
- 49.↵
- 50.↵
- 51.↵
- 52.↵
- 53.
- 54.↵
- 55.↵
- 56.↵
- 57.
- 58.
- 59.
- 60.
- 61.↵
- 62.↵
- 63.
- 64.
- 65.↵
- 66.↵
- 67.↵
- 68.↵
- 69.↵
- 70.
- 71.↵
- 72.↵
- 73.↵
- 74.↵
- 75.↵
- 76.↵
- 77.
- 78.↵
- 79.↵
- 80.↵
- 81.↵
- 82.↵
- 83.↵
- 84.
- 85.↵
- 86.↵
- 87.↵
- 88.↵
- 89.
- 80.↵
- 91.↵
- 92.↵
- 93.
- 94.↵
- 95.
- 96.↵
- 97.↵
- 98.↵
- 99.↵
- 100.↵
- 101.↵
- 102.
- 103.↵
- 104.↵
- 105.↵
- 106.
- 107.↵
- 108.↵
- 109.↵
- 110.↵
- 111.↵
- 112.↵
- 113.↵
- 114.↵
- 115.↵
- 116.↵
- 117.↵
- 118.↵
- 119.↵
- 120.
- 121.↵
- 122.↵
- 123.↵
- 124.↵
- 125.↵