Guidelines for the emergency management of asthma in adults

Canadian Medical Association Journal 1996; 155: 25-37

Résumé

© 1996 Canadian Medical Association (text and abstract/résumé)

Abstract

Most deaths from asthma are associated with the patient's and physician's failure to recognize the severity of the attack.[6-8,13] The implication of such observations is that inappropriate or suboptimal therapy results in poor disease control.

Although most deaths from asthma occur outside hospital, appropriate management of acute asthma in the emergency department will have an important impact.[7,14,15] Two recent Canadian reviews concluded that asthma was often undertreated in the emergency department and that the importance of routine spirometry in patients with acute asthma was generally underappreciated.[16,17] Optimal management of acute asthma in the emergency department includes aggressive treatment of the particular episode, recognition of the patient as being at high risk for future life-threatening attacks[18] and provision of a clearly written asthma management plan (including instructions for follow-up) to the patient at the time of discharge from the emergency department.[7] A survey report published in 1992 showed that 32% of patients with asthma presenting to a Canadian emergency department had never discussed a plan of asthma management with their physician and that an additional 37% had no plan at all.[19] Other investigators have found evidence of poor asthma control both before and after visits to the emergency department by patients with acute asthma.[16,17,20-24]

Although most people with asthma have a primary care physician, they still use the emergency department as an important point of contact with health care providers. Therefore, physicians, nurses and respiratory technologists in the emergency department can have a positive influence on asthma control, beyond the treatment of the acute attack.

There have been several large-scale attempts to develop asthma management guidelines,[25-30] but their focus has been on maintenance therapy with an emphasis on preventive strategies. Only a few have addressed the emergency management of acute asthma.[26-28] Also, previous efforts in developing guidelines have demonstrated weaknesses in the methods of evaluating the evidence and a lack of involvement of potential users in the development process.

The guidelines presented in this article were developed by the CAEP/CTS Asthma Advisory Committee, a committee of emergency physicians and respirologists representing the Canadian Association of Emergency Physicians (CAEP) and the Canadian Thoracic Society (CTS), who used the evidence-based approach recommended by the CMA.[31] The executive of CAEP appointed a chair and cochair to create a plan for assessing the need for guidelines, setting terms of reference and recruiting an advisory committee. A questionnaire evaluating practice norms and compliance with consensus statements available at that time was sent to CAEP members and all directors of emergency departments across Canada in November 1992. Emergency physicians from tertiary care centres and community hospitals across Canada were invited to participate in the development of the guidelines. The CTS and the College of Family Physicians of Canada were asked to appoint representatives to the advisory committee. Previously published guidelines, articles identified through a search of MEDLINE and Emergency Medical Abstracts, and information from committee members were the sources of evidence used in the development of the guidelines. The levels of evidence established by the Canadian Task Force on the Periodic Health Examination were applied.[32] Two consensus meetings were held in 1993 to review the proposed guidelines. A poster summary of the guidelines was reviewed by committees at CAEP and the CTS before final approval was granted by the executive of both organizations.

These guidelines concur with the opinions expressed in a recent review of the assessment and management of status asthmaticus[33] and share the principles of three recently published consensus statements (two national and one international).[26-28] However, only the evidence supporting the CAEP/CTS guidelines was graded. Differing philosophies of therapy and, to some extent, availability of certain drugs account for some of the variations between countries. (A table summarizing the similarities and differences of the guidelines and consensus statements is available from the corresponding author upon request.)

Recommendations

Therapy with ß2-agonists

Inhaled ß2-agonists produce the quickest relief of acute bronchospasm, with the fewest side effects.[34,47,49] Prior treatment with inhaled ß2-agonists (with the use of a metered-dose inhaler or a wet nebulizer) does not preclude successful reversal of airflow limitation in the emergency department.[41]

Drug administration

The inhaled route is preferred for the administration of bronchodilators in acute episodes of asthma. This has been confirmed in several small trials,[34,35,37,52-54] and two multicentre trials have clearly demonstrated that inhaled salbutamol is more effective and safer than intravenously administered salbutamol.[50,51] In the few studies claiming that the parenteral route was more efficacious,[57,58] the dose of inhaled bronchodilators was low by current standards.[26-29] Intravenous use of bronchodilators should be considered only if the response to nebulization is poor or the patient is coughing excessively, is moribund at presentation or becomes so despite inhalation therapy.

2b.  Bronchodilators should be titrated to effect using objective and clinical measures of airflow to guide the dose and frequency of administration (grade A recommendation; four level I trials[38,59-61] and two level II studies[62,63] [see also recommendations 5 and 6]).

The dose of inhaled or intravenously administered ß2-agonists needed to reverse an asthma attack cannot be standardized. A patient's ability to use the inhaled route, the efficiency of the delivery system, the relative amounts of bronchospasm versus airway narrowing due to inflammatory mucosal edema and secretions, and unpredictable patient factors such as reduced sensitivity or down-regulation of ß2-agonists in severe asthma all influence drug dosing.

Relief of bronchospasm with inhaled bronchodilators is best achieved if the principle of cumulative dosing is followed: sequential doses build upon the therapeutic effects of previously administered doses.[64-66] The frequency of dosing will be determined by the patient's response and by the time required to nebulize the dose completely, so that administering a dose every 15 to 20 minutes with a wet nebulizer, or even continuous administration with a wet nebulizer, may be necessary initially, because of the inherent low efficiency of these devices.[38,60-62,66,67] The optimal number of puffs from a metered-dose inhaler is not known. The British Thoracic Society states that 20 to 40 puffs may be necessary.[28] We recommend 4 to 8 puffs every 15 to 20 minutes in most cases of acute asthma. However, it may be necessary to increase the dosage to 1 puff every 30 to 60 seconds (up to 20 puffs if required). The dosage should be adjusted according to objective measures of airflow limitation and symptoms. Once maximum relief has been achieved, further administration of bronchodilators by any route will provide no further clinical benefit and, in fact, may result in toxic effects.

2c.  The use of a metered-dose inhaler, with or without a chamber (valved spacer device), is preferred over the use of a wet nebulizer for patients with mild to moderate asthma; a spacer device is recommended whenever the metered-dose inhaler is used for severe asthma (grade A recommendation; three level I trials,[59,68,69] four level II studies[70-73] and three level III reports[74-76]). Aerosol bronchodilator therapy given by wet nebulizer or metered-dose inhaler is at least equally effective for acute asthma.[59,70-74,77-79] For mild to moderate asthma, the addition of a spacer device to the metered-dose inhaler is not necessary because the inhaler on its own can be effective provided a multiple-puffing regimen is used.[74,80]

Two studies have claimed that the wet nebulizer was better than the metered-dose inhaler with a spacer device,[75,76] probably because eight to nine times more medication was administered with the nebulizer. It has been shown that more rapid and more profound bronchodilation is achieved when sufficient doses are given with a metered-dose inhaler plus spacer device than when conventional doses are administered with a wet nebulizer,[59,68,71] even in patients with the most severe airflow limitation (forced expiratory volume at 1 second [FEV1 of less than 0.67 L).[59] In one study[71] patients with severe asthma (those with an FEV1 of less than 30% of predicted) had significantly faster (30 minutes v. 60 minutes) and greater relief of airflow limitation and used seven times less salbutamol with a metered-dose inhaler plus spacer device than with a wet nebulizer. In another study[68] 6.5 times more salbutamol on average was required with the use of a wet nebulizer than with a metered-dose inhaler plus spacer device to achieve a maximum response.

All the studies demonstrating the superiority of metered-dose inhalers plus spacer devices showed similar therapeutic response plateaus, with maximum bronchodilation occurring after 800 to 1600 µg (8 to 16 puffs) of salbutamol.[59,68,71]

Compared with wet nebulizers, metered-dose inhalers plus spacer devices offer the advantages of greater cost savings, faster access to therapy, more efficient use of paramedic staff time and quicker achievement of maximum bronchodilation.[81-83] Administration of salbutamol with a metered-dose inhaler plus spacer device takes about 2 to 3 minutes for each treatment, as compared with 10 to 20 minutes for each treatment with a wet nebulizer. Quicker achievement of maximum bronchodilation permits earlier triage and discharge decisions.

Anticholinergic therapy

In all 10 controlled, double-blind studies of ipratropium bromide therapy for acute asthma in adults, the combination of ipratropium bromide with a ß2-agonist was superior to a ß2-agonist alone.[84-93] This combination was especially beneficial to patients with the most severe airflow limitation (an FEV1 of less than 1 L or a peak expiratory flow rate [PEFR] of less than 140 L/min): the mean increase in the FEV1 was 55.6%, as compared with 38.9% with a ß2-agonist alone.[85-88] In one study the combination of ipratropium bromide plus nebulized salbutamol, in addition to producing greater bronchodilation, was associated with fewer adverse effects (e.g., tachycardia and tremor) than were larger doses of ß2-agonists alone.[85]

In three trials nebulized ipratropium bromide alone produced initial bronchodilation equivalent to that achieved with an inhaled ß2-agonist (salbutamol or fenoterol), but because of its slower response time, ipratropium bromide alone is not recommended.[84,92,93] It may be particularly useful in treating bronchospasm provoked by ß-blockers.[94]

The optimal dose of nebulized ipratropium bromide for acute asthma is not clearly known, but it is generally accepted that 500 µg will produce the peak bronchodilator response in acute asthma (level III evidence).[95]

There have been no randomized studies of ipratropium bromide therapy for acute asthma administered with a metered-dose inhaler, with or without a spacer device, but one can reasonably expect that this method would be as effective as a wet nebulizer, provided adequate dosing is achieved (level III evidence; consensus opinion).

Aminophylline therapy

Aminophylline does not usually provide a significant, additive bronchodilator effect compared with adequate doses of inhaled ß2-agonists in cases of acute asthma[34,36,47,96,97] and, in fact, appears to be associated with an increased risk of adverse effects.[36,46,47]

Intravenous aminophylline therapy may have a role, however, in the treatment of patients with severe acute asthma admitted to hospital once the initial crisis in the emergency department has passed.[98,99]

It has been suggested that aminophylline may improve respiratory muscle function in acute asthma.[98,100] Indirect evidence that supports this role comes from a placebo-controlled study showing that despite no change in the FEV1 there was a reduction in the number of hospital admissions from the emergency department among patients given aminophylline.[101]

The weight of evidence is against the routine use of aminophylline early in the treatment of acute asthma. This conclusion is supported by a meta-analysis of 13 adequately designed trials involving patients with severe acute asthma.[96]

Intubation

5.  Ketamine and succinylcholine are recommended agents for rapid sequence intubation (RSI) in cases of life-threatening asthma (grade B recommendation; 11 level II-3 or level III reports[102-112]).

Since the patient's condition can deteriorate rapidly, once the decision has been made intubation should be accomplished as quickly and with as much control as possible using a modified RSI technique. Ketamine is recommended as the agent of choice because it has a rapid response time, provides good levels of anesthesia and is a good bronchodilator (level III evidence).[102-104] Ketamine has been reported to be useful in the treatment of severe bronchospasm refractory to conventional bronchodilators and may obviate the need for endotracheal intubation in this setting.[105-110] Pretreatment with benzodiazepines helps prevent the occasional emergence reactions (hallucinogenic episodes) associated with ketamine.

Immediately after administration of the sedative, paralysis should be induced with succinylcholine because it has the fastest response time and the shortest duration of action of drugs in its class. This is important if the intubation is unsuccessful. Paralysis following intubation should be maintained using vecuronium (0.15 mg/kg intravenously). Bag-and-mask ventilation does not precede intubation in an RSI technique and should be used only in failed attempts. It is difficult or even impossible to use bag-and-mask ventilation in cases of acute asthma because of severe hyperinflation and it may cause harm by provoking gastric distention and an increased risk of aspiration.

Management of refractory cases

Parenteral bronchodilator therapy is 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 (level III evidence; expert panel [see recommendations 2 a and b]).

Patients with bronchospasm receiving ventilation who do not respond to conventional bronchodilator therapy may benefit from an inhaled anesthetic agent with bronchodilating properties, such as ether,[113] halothane,[114-117] enflurane[117] and isoflurane.[118,119] 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 for a successful outcome.[32,120-122] Because of extreme hyperinflation, it is often difficult or nearly impossible to use ventilation because of the combination of severe restrictive and obstructive defects. Ventilation strategies emphasize caution with attempts to abruptly reduce the partial pressure of carbon dioxide to normal levels.[120-122] It is advisable to follow a controlled mechanical hypoventilation approach that accepts moderate to high degrees of hypercarbia until lung function improves, with occasional intravenous administration of bicarbonate in order to keep the pH level above [7.2.120-122] The risk of barotrauma and volutrauma (shock) can be minimized with slow machine rates (6 to 8 breaths/min) allowing a low inspiration/expiration ratio and with low tidal volumes (6 to 8 mL/kg). With ventilation patients may also require frequent suctioning of mucous secretions often seen in life-threatening attacks.

Objective measurement of airflow

It has been consistently shown that the severity of airflow limitation in asthma attacks correlates poorly with the traditionally assessed clinical signs (e.g., wheezing). Many patients may have near-normal physical findings yet will have clinically important signs of airflow limitation when spirometric tests are performed. Similarly, changes in clinical signs after treatment do not always reflect changes in spirometric test results. Furthermore, it has been shown that physician estimates of PEFR are frequently inaccurate.[123]

The standard outcome measures used in the emergency department to assess the severity of airflow limitation are the FEV1 and the PEFR.[128] There is a high correlation between these two measurements following bronchodilator therapy.[129] When possible, the best value of three attempts at each measurement should be recorded. Because optimal results depend on patient effort, specially trained personnel (respiratory therapist, nurse and physician) should be present to monitor the test procedure.[128] The measurement of FEV1 and PEFR is not recommended in moribund patients or those who appear confused, cyanotic or exhausted.

7b.  The optimal way to record the FEV1 or PEFR is the percent of predicted or, ideally, the percent of previous best (grade C recommendation; three level III reports[26-28] and consensus opinion).

Results from two studies suggest that the percent predicted values are not more useful than absolute values in making clinical decisions.[129,130] However, the subjects were less than 40 years of age and were unlikely to have had any component of fixed airway obstruction (e.g., chronic obstructive pulmonary disease). To be consistent with all patient groups we recommend that the FEV1 and the PEFR be recorded as the percent of previous best, if known, or the percent of predicted based on simple nomograms. This is consistent with other consensus guidelines.[26-28]

7c.  The FEV1 or the PEFR should be measured before bronchodilator therapy has been started and after it has been completed (grade A recommendation; one level I trial,[131] one level II study[129] and two level III reports[127,132]).

Physician estimates of response to therapy are often inaccurate in acute asthma.[123] Several studies have shown that failure of initial bronchodilator therapy to improve the FEV1 or the PEFR substantially is predictive of a more prolonged attack course, or even of the need for hospital admission.[36,132] Thus, objective measurement after the completion of bronchodilator therapy is the best method of predicting outcome of the asthma attack (see recommendation 8).

7d.  All patients should be informed of their post-treatment spirometric test results when they are discharged (grade C recommendation; consensus opinion).

Patients will be able to pass this information along to other clinicians. Knowledge of the spirometric test results may allow both the patient and the clinician to determine the most appropriate approach to the disposition of the patient after treatment of subsequent asthma attacks.

Discharging patients from the emergency department

• Patients with a pretreatment FEV1 or a PEFR of less than 25% of previous best or of predicted (an FEV1 of less than 1.0 L or a PEFR of less than 100 L/min) usually require admission to hospital (grade B recommendation; one level II study[132]).
• Patients with a post-treatment FEV1 or a PEFR of less than 40% of previous best or of predicted (an FEV1 of less than 1.6 L or a PEFR of less than 200 L/min) usually require admission to hospital (grade A recommendation; one level I study[131]).
• Patients with a post-treatment FEV1 or a PEFR of 40% to 60% of previous best or of predicted (an FEV1 of 1.6 to 2.1 L or a PEFR of 200 to 300 L/min) are possible candidates for discharge (grade C recommendation; consensus opinion).
• Patients with a post-treatment FEV1 or a PEFR of more than 60% of previous best or of predicted (an FEV1 greater than 2.1 L or a PEFR greater than 300 L/min) are likely candidates for discharge (grade A recommendation; one level I trial[131] and two level II studies[129,133]).

Important factors that define a patient at high risk for relapse include the following: (a) hospital admission or visit to the emergency department in the previous 12 months, (b) recent corticosteroid use, (c) use of multiple categories of asthma medication, (d) previous severe or life-threatening asthma attack, (e) presence of psychosocial problems[7,10,134] and (f) the frequent, regular use of inhaled ß2-agonists.[135-137]

Corticosteroid therapy

Corticosteroid therapy has been shown to be clinically efficacious in the treatment of acute episodes of asthma. In placebo-controlled trials corticosteroids were found to be associated with rapid resolution of airflow limitation in admitted patients[138] and a decrease in the relapse rate among those discharged from the emergency department.[139,140] No subgroup of emergency patients have been prospectively identified who do not benefit from corticosteroid therapy. Post-hoc analysis in a study of the role of corticosteroids in patients discharged from the emergency department[140] suggested that the effect of oral corticosteroids in reducing the relapse rate may be confined to patients with an FEV1 of less than 60% of predicted on discharge. On the basis of expert consensus opinion (grade C recommendation), systemic corticosteroid therapy may be omitted in occasional cases of very mild asthma (an FEV1 or a PEFR of more than 60% of predicted), in which the patient has no markers of risk for asthma-related death or for readmission.

9b.  Corticosteroids should be administered as soon as possible after initiation of bronchodilator therapy (grade A recommendation; meta-analysis[141] of three level I trials[142-144]).

Despite a conflicting conclusion in one study,[138] a meta-analysis[141] of three relevant studies[142-144] revealed that the early administration of corticosteroids (within 30 minutes) significantly reduces hospital admission rates.

9c.  Oral and intravenous routes of corticosteroid administration are equally efficacious (grade A recommendation; four level I trials[145-148]).

For admitted patients intravenous corticosteroid therapy has no advantage over oral therapy regarding the rate of resolution of airflow limitation.[148] Since the onset of anti-inflammatory effects of corticosteroids are not seen for several hours, it is sufficient to administer corticosteroids orally to most patients in the emergency department. 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 readily absorb an oral dose (e.g., because of vomiting). For patients with severe symptoms intravenous corticosteroid therapy may have an early effect (within 1 to 6 hours) by reversing ß2-receptor down regulation seen in chronic ß2-agonist use.[149]

In studies involving patients admitted to hospital, no clear trends emerged regarding the appropriate intravenous dose of corticosteroids. Studies that failed to delineate a benefit between high-dose and low-dose intravenous corticosteroid therapy were not double-blind (level II studies),[150-153] had samples that were too small to achieve adequate statistical power (level II study),[152] involved patients with mild disease[154] or had cointervention or variable doses of oral corticosteroid in the low-dose groups.[155] Only one level I trial[156] has shown a positive dose-response relation between high-dose and low-dose regimens. The findings of two reviews indicated that a sufficient intravenous dose is 100 to 200 mg of methylprednisolone (or equivalent) per day or 500 to 1000 mg of hydrocortisone (or equivalent) per day.[157,158] Methylprednisolone is the more expensive of the two but has less mineralocorticoid activity. It is likely that any parenterally administered corticosteroid (dexamethasone, methylprednisolone, hydrocortisone) will be equally efficacious if given in equivalent doses. If the oral route is chosen, doses equivalent to 40 mg of prednisone orally are recommended.[141]

Oral corticosteroid therapy after discharge

Out-patients with exacerbations of asthma have been found to respond, in a dose-related fashion, to increased doses of prednisone from 0.2 to 0.6 mg/kg per day (14 to 42 mg of prednisone per day for a 70-kg adult).[159] Placebo-controlled trials of oral corticosteroid therapy involving patients discharged from the emergency department have shown a decrease in the relapse rate with the use of a dose equivalent to 40 mg of prednisone per day.[139,140] No trials have compared oral prednisone regimens starting at doses higher than 40 mg/d. It is not known whether a higher initial dose of prednisone would be efficacious; however, some experts recommend up to 60 mg as the initial dose.[158] The range of 30 to 60 mg/d reflects a dose of 0.6 mg/kg per day for patients 50 to 100 kg. The minimum duration of oral corticosteroid therapy following discharge that has been studied has been 8 days,[139,140] but up to 14 days of treatment may be needed to achieve a maximum response.[159] No tapering appears to be required to prevent a recurrence of asthma symptoms during this period.[159] Physicians should individualize the drug regimen. Longer than 14 days of treatment may be required for patients with a history of corticosteroid dependence or multiple recent exacerbations. These patients should be referred to an asthma specialist or clinic for close out-patient follow up.

Inhaled corticosteroid therapy

In one study, inhaled corticosteroid therapy was compared with a placebo after a 14-day nontapered course of oral corticosteroid therapy in ambulatory patients with unstable asthma.[161] The other study compared tapering and nontapering of corticosteroid therapy in patients with acute episodes of asthma receiving inhaled corticosteroid therapy.[160] The conclusions of the two studies were similar: there was no significant worsening of spirometric test results after termination of the nontapered oral regimen in patients receiving inhaled corticosteroid therapy. The inhaled dose varied from 1500 µg/d61 to a mean of 908 µg/d (range 400 to 2000 µg/d).[160]

The recommended dose at discharge of inhaled corticosteroids (beclomethasone or budesonide) is 500 to 1000 µg/d, but this may depend on the dose and duration of oral corticosteroid therapy (grade C recommendation; expert panel opinion). The more markers of risk for asthma-related death or readmission in the patient's history,[18,134,136] the higher the recommended dose of inhaled corticosteroids.

Discharge treatment plan and follow-up care

Most experts believe that educating patients about asthma is the key to optimal disease control.[7,11,26-28,33] Proper drug-delivery technique should be ensured and compliance optimized through improved understanding of the pathophysiologic features of asthma and the pharmacologic characteristics of the drugs. Although there are practical and theoretical deterrents to comprehensive education in the emergency department, the principles used in the development of action plans should be applicable in any situation. Asthma clinics and teaching centres have been successful in reducing absenteeism, the number of hospital admissions and visits to the emergency department, and the use of corticosteroids and ß2-agonists.[162-167] Whenever possible, emergency staff should develop brief written treatment plans with clear instructions for follow-up care and review of drug- delivery techniques (grade C recommendation; level III evidence [consensus opinion]).

This project was sponsored by the Canadian Lung Association, Glaxo Canada Inc., Astra Pharma Inc. and Fisons Pharmaceuticals.

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