Introduction
The motivation for producing guidelines for treating adult asthma is the same as that for children; the belief being that a more uniform approach ensures that the greatest number of asthmatics are offered the most effective and affordable management of their condition. Guidelines published in other countries are not necessarily directly applicable to the South African situation. In this chapter the guidelines for both chronic persistent asthma and for acute asthma are combined.
Management of chronic persistent asthma
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Aims of management
The aims of management in adults are:
- to recognise asthma
- to abolish symptoms
- to restore normal (or best possible) long-term function of the lung
- to reduce the risk of a severe attack.
These aims are achieved by avoiding recognised causes or aggravating factors and by using the lowest effective dose of convenient treatment with minimal short- and long-term side-effects. Emphasis is placed upon the early use of anti-inflammatory drugs, objective monitoring of the progress of asthma using peak expiratory flow meters, and active patient involvement in monitoring and managing their condition.
Treatment is undertaken in a step-wise manner as described below (and in Fig. 1), commencing at the point appropriate to the severity of the patient’s condition. All changes of treatment should be made on the basis of objectively recorded measures of response, i.e. the clinical condition, as well as measures of lung function. A short course of oral corticosteroids may be needed at any tome to control asthma. See below:
Avoidance
If agents such as allergens, occupational sensitising chemicals, and certain drugs, e.g. aspirin and non-steroidal anti-inflammatory drugs, are known to induce asthma in a patient, they should be avoided if possible. Beta-blockers are contraindicated in patients with asthma. Avoidance of day to day triggers such as exercise and cold air generally imposes inappropriate restrictions on life-style, and it may be preferable to adjust treatment to cover exposure to these (see ‘Special clinical situations’ below). Both active and passive smoking should be discouraged.
Treatment with short courses of oral steroids (prednisone)Short courses of oral steroids may be needed to control exacerbations of asthma; these courses are usually given for 2 weeks only. Indications are:
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Bronchodilators
In chronic persistent asthma, a B-2-agonist should be used ‘as required’ or regularly in recommended doses. Patients with mild and infrequent symptoms should preferably be treated with a B-2-agonist as required. When symptoms become persistent, the regular use of B-2-agonists as well as anti-inflammatory agents is recommended. Inhalation is the preferred means of administration; the drug is delivered direct to the airway, doses are small, and side-effects are minimised. In patients with normal lung function who have only infrequent symptoms and no sleep disturbance, B-2-agonists may be used as required.
Inhaled anti-inflammatory agents
Patients who need to inhale a bronchodilator more than once daily or who have night-time symptoms require regular inhaled anti-inflammatory drugs. Options include corticosteroids, sodium cromoglycate and nedocromil sodium. Inhaled steroids are the drugs of choice (because of their universal effectiveness and relatively low cost); the sarting dose of either beclomethasone dipropionate or budesonide is 100-400 ug twice daily. For patients with poor inhaler technique, dry powder steroid devices may be prescribed although these are more expensive. Patients with persistent symptoms (especially nocturnal asthma), a continuing need for inhaled bronchodilators and sub-optimal peak flow rates may require a higher or more frequent dose of inhaled steroids. Once symptoms and peak flow have improved and stabilised for a month or longer, the dose of inhaled steroids is gradually reduced to the minimum that maintains countrol. If control is not achieved (as judged in terms of frequent symptoms, increased use of an inhaled B-2-agonist, and low peak expiratory flow), compliance should be questioned and the patient’s inhaler technique checked. If these are found not to be readily correctable, consideration should be given to a dry powder formulation or the substitution of oral corticosteroids.
Additional therapy
Failure to control symptoms with regular inhaled B-2-agonists in combination with standard doses of inhaled steroids (up to 800 ug per day, using standard dosage formulations) leaves one with three therapeutic options: (i) the additon of xanthines or slow-release oral B-2-agonists or long-acting inhaled B-2-agonists; (ii) low-dose oral prednisone therpay, using an alternate-day regimen not exceeding 10 mg per day in the long term; and (iii) a further increase in the dose of inhaled corticosteroids (up to 1 mg per day). It should be noted that if the dose of inhaled corticosteroids exceeds 1000 ug per day, the potential advantages of the inhaled route are lost since unwanted effects (e.g. suppression of the adrenal-pituitary-hypothalamic axis and oral candidiasis) become more prominent; in additon the much greater expense of hihg doses of inhaled corticosteroids would warrant the use of oral prednisone.
Oral B-2-agonists or long-acting inhaled B-2-agonists or xanthines should not be used as first-line (step 1) drugs. Their main indication is the presence of symptoms (often at night) which are not controlled by anti-inflammatory drugs and standard doses of inhaled B-2-agonists. A single nocturnal dose of slow-release preparation may be adequate but a twice-daily regimen may be necessary. Any of these three types of bronchodilator may be effective and each may be tried in turn, in indivudal patients. Each patient should however be shown to benefit from the treatment before including it as part of their long-term treatment. For optimal effect, the individual’s correct therapeutic dose xanthine should be determined through monitoring of blood xanthine concentrations. Long-acting oral and inhaled B-2-agonists should not normally be used without concurrent anti-inflammatory treatmetn and it should be recognised that they add significantly to the drug bill.
Caution regarding bronchodilator preparations
Combination tablets
Although these are often relatively inexpensive, their formulation and constituents are far from ideal, may have harmful effects and may tend to be of low potency in controlling chronic asthma. Most contain a relatively lose dose of xanthine. Some contain ephedrine and sedatives like phenobarbitone which have no place in the modern management of asthma. In addition, phenobarbitone increases the metabolism of xanthine and renders it less effective.
Duplications of drugs within one class
This is hazardous and practitioners should be well acquainted with the trade names of preparations in diffrent classes. The use of more than one type of short-acting B-2-adrenergic inhalant or more than one type of oral xanthine is potentially hazardous.
Maintenance treatment with high-dose (>10 mg prednisone-prednisolone) oral corticosteroids.
While highly effective and inexpensive, these agents have serious dose-related side-effects. Careful efforts should therefore be made to establish the lowest dose (preferably a single alternate-day dose regimen) which achieves satisfactory control. Patients who require high-dose oral corticosteroids (>10 mg per day) should preferably be referred to a specialist.
Step-down
When symptoms and use of bronchodilators is low and pulmonary function tests (e.g. PEFR) suggest that the asthma is well controlled, a step-wise redution in the dose of anti-inflammatory drugs may be possible. Patients on oral steroids for control of chronic persistent asthma should be stable for 3-6 months before slow, step-wise reduction (at a rate of not more than 5 mg prednisone a month) may be undertaken. Lung function should be monitored during the step-down periods, and patients should be given written instructions about the action to take if PEFR results get worse.
Other drugs and unproven treatments
Antihistamines, including ketotifen, have proved disappointing in clincal practice. Immunosuppressive treatment is not recommended as a routine treatment. There is anecdotal evidence that some patients have benefited from the use of ionisers, exclusion diets, acupuncture or homeopathy, but controlled clinical trials have so far been disappointing. Conventional treatment should be continued if these treatments are tried. Hyposensitisation (immunotherapy) is not indicated in the management of asthma and may be hazardous.
Cost compromises
The above outline of management is viewed as ideal therapy. However, faced with the high cost of some therapeutic agents, the following compromises may be considered.
- Oral prednisone is significantly cheaper than high-dose inhaled corticosteroid preparation.
- Xanthine preparations may be used as first-line drugs. However they are significantly less effective than those in the protocol (see Fig. 1). In addition, a major difficulty with the use of xanthines is the determination of the correct dose for each patient. The use of usual ‘recommended doses’ results in sub-optimal blood levels in a large proportion of patients.
- Short-acting xanthine preparations are significantly less expensive than slow-release preparations. However, the latter promote compliance and have a better absorption profile.
- Use of dry powder formulations for inhalation therapy is more expensive than metered-dose inhaler treatment. However, in patients who have poor co-ordination, some of the dry powder formulations may have significant advantages over the metered-dose inhalers.
- Doctors are encouraged to consider the cost-effectiveness of agents at all stages of treatment. Efforts should be made to avoid concurrent use of expensive agents with marginal additional advantages. Although newer agents may have individual merits, their use involves considerable cost with a generally small gain over less expensive alternatives.
Special clinical situations
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Nocturnal asthma
This is usually an indication that the asthma is poorly controlled, and is associated with a high risk of death. Therapy should include stabilisation of the baseline with adequate anti-inflammatory therapy (preferably inhaled or oral corticosteroids) as well as long-acting bronchodilators (step III in Fig. 1).
Exercise-induced asthma (EIA)
EIA, in association with other manifestations of poor control, should be managed in the same way as nocturnal asthma. As an isolated symptom, effective control may be achieved with inhaled B-2-adrenergic agents 15-20 minutes before exercise. Sodium cromoglycate is an alternative and might provide additional protection against EIA. However, it is effective in a smaller proportion of patients than is the B-2-agonist.
Elderly patients
The elderly are particularly susceptible to xanthine toxicity. Ipratropium bromide has significant advantages over B-2-adrenoceptor agents, both in terms of efficacy and tolerance. Special caution should be employed in the use of oral steroids as these may lead to fluid retention and accelerated osteoporosis.
Cardiac disease and hypertension
Patients with cardiac disease and hypertensive patients are prone to certain side-effects of asthma preparations. Oral corticosteroids may precipitate fluid retention and induce hypokalaemia. The latter may also result from oral and intravenous B-2-agonist use and might compound diuretic-induced hypokaelamia, as well as causing arrhythmias.
Pulmonary tuberculosis
The routine use of isoniazid in patients with radiographic evidence of ‘healed’ pulmonary tuberculosis (whether previously treated or not) is not recommended, as the risk of reactivation has not been shown to increase with corticosteroid use.
Diabetes mellitus
Special caution is required when introducing oral corticosteroids.
Thyrotoxic patients
These patients are particularly prone to the side-effects of B-2-agonist which in turn might be misinterpreted as signs of inadequately treated thyrotoxicosis. Worsening asthma is a feature of uncontrolled throtoxicosis and improves when the patient is rendered euthyroid.
Pregnancy
No modification of recommended treatment is necessary during pregnancy. Pregnant asthmatics require closer supervision and better control, because hypoxia during episodes of acute severe asthma is hazardous to the foetus.
Menstruation
This is often associated with transient worsening of the asthma. If such worsening is severe, it may be relieved or avoided by the use of a short course of low-dose corticosteroids towards the end of each menstrual cycle.
Surgery and general anaesthesia
These are sometimes associated with worsening asthma. The anaesthetist should always be warned that the patient is an asthmatic. Patients on corticosteroids should receive an additional dose before and/or during induction and be closely monitored post-operatively for possible unstable asthma.
Acid reflux
This is an established cause of bronchospasm in a minority of patients. Investigations for acid gastic reflux are indicated in patients with symptoms suggestive of reflux and may be appropriate in some cases of severe, brittle asthma.
Nebulised B-2-agonist
The routine prescription of nebulised B-2-agonists should be avoided. Patients’ perceived need for a nebuliser usually reflects poor control, which can be rectified by conventional treatment, including intensification of anti-inflammatory therapy accompanied by education about maintenance treatment and a ‘crisis plan’ (see below).
Guidelines for giving nebulised bronchodilators for chronic persistent asthma
This is not a form of maintenance therapy. Before prescribing nebulised bronchodilators:
(i) the diagnosis should be reviewed and confirmed; (ii) other steps in management should be optimised, including a short course of increased maintenance oral steroids; (iii) use of the nebuliser must have been shown to achieve improved bronchodilatation, without significant side-effects.
Re-assessment: Use at home should be reviewed after 3 weeks with a view to withdrawing nebulised B-2-agonsit therapy. If use of the nebuliser is required more than 3 times a day, hospital admission is indicated.
Supervision: Verbal and written instructions should be given to the patient on the method and frequency of use, the action to be taken in the event of worsening asthma, and when to attend for follow-up visits. Supervision should normally entail regular visits to a doctor and should include evaluation of peak expiratory flow rates, monitoring of prescriptions, and bi-annual servicing of the compressor.
Guidelines for self-management of asthma
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Patients are encouraged to participate in informed decision-making as regards treatment. The guidelines for self-management of asthma are as follows:
- The overall aim is to train patients as far as possible to recognise alterations in the pattern of their asthma and to make time timeous and appropriate changes to their therapy.
- Patients should have an understanding of the nature of asthma and its treatment, including
- (I) training in the proper use of inhaled drugs and the use of a peak flow meter;
- (ii) knowledge of the difference between palliative (пїЅrelieverпїЅ) and anti- inflammatory (пїЅpreventerпїЅ) treatment; and
- (iii) instruction to ensure recognition of signs that asthma is worsening. Patients should be conscious of the importance of nocturnal symptoms and changes in peak expiratory flow rate.
- Patients should be given clear instructions to avoid tobacco smoke and other recognised precipitants of asthma.
- Patients should be given realistic goals and should have a balanced view of the possible side-effects of the treatments.
- Education and training of patients are the responsibility of the doctor but can be shared with specially trained health care professionals. Advice should be consistent and repeated; it may be supported with written or audio-visual material.
- Patients who have required or who are likely to require a course of systemic corticosteroids should be trained to initiate or increase doses of inhaled and oral corticosteroids themselves under specified pre-arranged circumstances, as outlined in a self-management plan.
- The three elements of a self-management plan are: (I) monitoring of symptoms, peak flow, and drug usage leading to (ii) the patient taking pre-arranged action according to (iii) written guidance. Such self-management plans should be carefully discussed with the patient and written down.
- A written crisis-management plan should be given to each patient; it should include details of how to obtain access to immediate medical attention.
- Patients should regard the plan of management as subject to a process of continuing but orderly review in which they plan an active part. A review of the patientпїЅs progress at a pre-arranged visit to the doctor should take cognisance of the following: (I) symptoms – especially nocturnal; (ii) interference with normal activities (e.g. work loss); (iii) the patientпїЅs own record of treatment changes; (iv) peak flow recordings; (v) understanding of asthma; (vi) understanding of management; (vii) inhalation skills; and (viii) the action to be taken by the patient if signs of deterioration develop.
- Requests for help from a patient with asthma should be accorded high priority by doctors. Other health care workers should be aware that medical help may be required promptly in the event of worsening asthma.
- Arrangements should be made for a пїЅMedic-AlertпїЅ bracelet or locket to be issued to asthmatic patients, particularly those who are steroid-dependent, those know to be hypersensitive to non-steroidal anti-inflammatory drugs, and those with пїЅbrittleпїЅ asthma.
Referral to a specialist physician
Referral to a specialist should be considered in the following situations (i) patients in whom there is doubt about the diagnosis, e.g. the elderly; smokers or former smokers with a wheeze; those with unexplained persistent cough;
(ii) patients with possible occupational asthma; and
(iii) patients with asthma who present a problem in management, e.g. those who have recently been discharged from hospital; those with catastrophic or sudden severe attacks of asthma (i.e. пїЅbrittleпїЅ) asthma; those with continuing symptoms despite high doses of inhaled steroids; those being considered for long-term treatment with nebulised bronchodilators; pregnant women with worsening asthma; and patients whose asthma is interfering with their life-style.
Patients with asthma need regular supervision and support from a doctor who is knowledgeable about the condition. Arrangements for referral and long-term care vary from district to district and according to the special interests of general practitioners, but there should be regular liaison between the specialist and primary health care provider.
Management of acute asthma
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Acute asthma (;acute asthma attackпїЅ) is usually an exacerbation of chronic asthma, and presents as worsening shortness of breath, cough, wheeze and chest tightness, or combinations of these symptoms often with apparent non-responsiveness to usual bronchodilator treatment. It may range from mild to life-threatening and is always associated with a fall in expiratory airflow measured as peak expiratory flow rate (PEF) or forced expiratory volume in one second (FEV1). The latter serve as more reliable indicators of severity of airflow obstruction than the severity of symptoms.
Exacerbations usually develop over hours or days, but occasionally occur precipituously over minutes either spontaneously or after exposure to allergens, noxious agents or other trigger factors. Slower deterioration usually reflects failure of long-term management.
Aims of management of acute asthma
Prevention of even mild exacerbations is the goal of maintenance treatment. The treatment of acute asthma is crisis- and hosptial-orientated; besides carrying a greater risk of death, brain damage, barotrauma and other complications of resuscitation, it is more costly. Fear , anxiety and disruption of normal activities are inevitable. Fatal attacks are often associated with: (I) under-estimation of the severity of the attack by patients, their relatives and their doctors, (ii) failure to initiate treatment promptly; and (iii) under-treatment of the exacerbation. Aims of management are to prevent this morbidity and mortality by: (I) relieving airflow limitation as rapidly as possible; (ii) relieving hypoxaemia; (iii) restoring lung function to normal as soon as possible by treating airway inflammation and reactivity; (iv) providing a suitable plan to avoid future relapses; and (v) providing a written action plan to be followed early in future attacks. The current guidelines apply to acute asthma and not to chronic bronchitis and emphysema caused by cigarette smoking. Although some of the principles of treatment in these conditions are similar, there are important differences. For example, in the latter, airflow obstruction is largely irreversible, and the free use of oxygen may precipitate carbon dioxide retention and worsen respiratory failure.
Recognition and assessment of severity of attacks
The assessment is based upon a variety of clinical signs and measurement of PEF or FEV1 (in all cases), and when available, assessment of blood gas status or oxygen saturation (Table 1). The table serves only as a guideline for deciding the initial course of action. CAUTION: Patients with severe or life-threatening attacks may not appear distressed and not all features of a severe attack may be present. The presence of any of these features indicates deterioration to the corresponding grade of severity. A severe grade should be assumed if the attack progresses quickly or if, on the basis of his/her history, the patient is considered to be at high risk of an asthma-related death.
PEF measurements
Lower PEF rates are most easily interpreted when expressed as a percentage of the predicted normal value for the individual (Table II) or of the patientпїЅs best value obtained previously when on optimal treatment. If neither of these is known, a decision must be made on the basis of the absolute value recorded, remembering that normal values vary with age, sex, height; older people, women, and shorter people have a lower normal range. Values for PEF and FEV1 expressed as percentages of the predicted normal are less useful in patients with chronically impaired lung function.
Arterial blood gases
Arterial blood gases should be measurement:
(i) all patients with clinical features of severe or life-threatening asthma (including all in the high -risk category and with PEF or FEV1 <50% for the predicted value or the patientпїЅs best); and
(2) oxygen saturation on pulse oximetry of less than 90%.
The determination of arterial blood gas status must not delay initiation of treatment.
| Moderate | Severe life-threatening | Respiratory arrest imminent (if any of listed signs present) | |
|---|---|---|---|
| PEF after initial bronchodilator* | Approx. 50-75% | <50% | <100 1/min |
| Breathlessness | Talking Prefers sitting |
At rest Hunched forward |
Exhaustion |
| Talks in | Phrases | Words | |
| Alertness | Usually agitated | Usually agitated | Drowsy or confused |
| Respiratory rate | Increased | Often >30/min | |
| Accessory muscles and supraternal retraction | Usually | Usually | Paradoxical thoraco-abdominal movement |
| Wheeze | Loud | Usually loud | Absence of wheeze |
| Pulse/min | 100-120 | >120 | Bradycardia |
| Pulses paradoxus (inspiratory fall in systolic blood pressure) | May be present 10-25 mmHg | Often present | Absence suggests respiratory muscle fatigue |
| PaO2 (on air) | >8 kPa (60 mmHg) | >25 mmHg <8kPa Possible cyanosis | Cyanosis |
| PaCO2 | <6kPa (45 mmHg) | >6kPa | |
| SaO2 (on air) | 91-95% | <90% |
| Blood gases are advised for all patients admitted to hospital with features suggesting severe asthma. *PEF expressed as percentage of normal value (read off Table II (Contact us for this table); according to age, sex and height, or the patientпїЅs best PEF value obtained when on optimal treatment. |
Assessment of high risk
Patients with the following history are at high risk of respiratory arrest and any attack must be considered severe: (I) current use of, or recent withdrawal from systemic corticosteroids; (ii) emergency care and/or hospitalisation for asthma in the past year or recent treatment for acute asthma; (iii) previous resuscitation and intubation for acute severe asthma; and (iv) previous sudden severe attack/s with few or no warning features in spite of regular treatment. When these attacks occur repeatedly it is termed “brittle asthma”.
Management of exacerbations
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Home management of exacerbations (Fig.2)
All patients with chronic asthma should have a written plan of action outlining how to recognise warning signs of deteriorating asthma, adjust treatment and obtain emergency medical care.
Warning signs of worsening asthma
These are: (I) increased need for and use of bronchodilator; (ii) apparently decreased effectiveness of a bronchodilator (partial or short-lived response); (iii) symptoms of asthma at nigh (disturbing sleep); (iv) early morning waking (“morning dipping”); (v) persistent cough; (vi) impaired ability to perform daily activities; (vii) increased diurnal variation in PEF rate; and a downward trend in PEF readings.
Adjusting treatment
The scheme of advice given to patients is presented in diagrammatic form in Fig.2. Initial treatment involves immediate use of repeated high doses of inhaled B-2-agonists. Where the response is incomplete or short-lived, additional therapy is indicated. However, even when the response is good, full recovery is often gradual, and modification of maintenance asthma medication is necessary.
Emergency medical care
Patients should seek medical help without delay if: (I) they have been identified as at high risk – they should be aware of this; (ii) the exacerbation is severe (Table 1); (iii) the response to bronchodilator is not prompt or not sustained for at least 3 hours; (iv) there is no sustained improvement in PEF within 4 – 6 hours of corticosteroid treatment; or (v) there is further deterioration.
Management of exacerbations by medical/nursing personnel
The observations that follow apply to treatment given by medical and/or nursing personnel at the clinics, consulting rooms, emergency departments or hospital.
Principles of Treatment
1. Begin treatment immediately:
2. Oxygen
Use the highest concentration mask and set at a high flow rate. Oxygen nasal cannulas may be used if a mask is not tolerated but they only deliver low concentrations of oxygen. Retention of carbon dioxide is not aggravated by treatment with oxygen in patients with acute severe asthma. The target oxygen saturation is 90% or more.
3. Primary drug treatment for acute asthma
This entails: (I) repeated use of high doses of inhaled B-2-agonists to relieve bronchospasm; and (ii) corticosteroids (usually by mouth or intravenously) to reduce bronchial inflammation and hyperactivity. High doses of inhaled B-2-agonists are given by nebulization or through a large spacer device attached to a metered dose inhaler (MDI). To ensure oxygenation, oxygen-driven nebulisation is recommended over air driven nebulisation. The initial treatment is one dose every 20 minutes for 1 hour. Dosing of nebuliser solutions (diluted 1:4 with normal saline) is as follows: fenoterol 1 mg, hexoprenaline 0.25 mg or salbutamol 5 mg. Subsequently, hourly administration or even continuous nebulisation should be given if the episode is severe.
If a nebuliser is not available, a large dose of B-2-agonist can be given via multiple actuations of an MDI into a large spacer device up to the total dose delivered by nebuliser. The spacer device should have a volume greater than 500 ml. Commercial models include Volumatic (Allen and Hanbury) and Nebuhaler (Astra), and doses may be administered through a mouthpiece or specially designed mask. Where these spacers are not available, a plastic bottle of similar size, with the base cut out to fit snugly over the mouth and nose, may be used. The patient is instructed to take several deep breaths from the spacer after each pair of actuations. In the home 4-10 puffs are recommended but may be repeated within minutes if the response remains poor, and while transport to a doctor or clinic is being arranged. (Fig.2) In the emergency room a total of 20 or more puffs (with limit of 50 puffs) may be given.
The early use of systemic corticosteroids is strongly recommended; their under-use has been linked with asthma deaths and early relapse. They speed up resolution and prevent relapse and should be commenced without delay, as they take at least 4 hours to produce clinical improvement. An advantage of intravenous over oral treatment has not been demonstrated and the former is considerably more expensive. However, because gastro-intestinal absorption is suspect in severe attacks, the intravenous route is advised, at least for the initial dose to ensure early peak dosing.
Corticosteroids benefit all patients but are essential when:
(i) the exacerbation is moderate;
(ii) the initial inhaled B-2-agonist dose fails to achieve significant improvement;
(iii) the patient develops acute asthma despite the regular use of oral corticosteroids; or
(iv) previous exacerbations required oral corticosteroids.
Usual doses are prednisolone, methylprednisolone or prednisone 30-60 mg as a single oral daily dose (usually in the morning) or hydrocortisone 200 mg intravenously 4-6 hourly, or methylprednisolone 125 mg twice daily intravenously. Corticosteroids should be continued for a 125 mg twice daily intravenously. Corticosteroids should be continued for a week after all symptoms of asthma have disappeared, i.e. at least 10 days. By that time the long-term preventive treatment plan should have been commenced or re-established. In patients taking inhaled steroid therapy, short courses of oral corticosteroid may be stopped abruptly without пїЅtaperingпїЅ the dose, as they are not associated with sustained adrenal suppression. However, when a patient has been taking oral steroids constantly or frequently, slow reduction of the dose is advisable. Due attention should also be paid to pre-existing conditions that might be adversely affected by higher doses, e.g. peptic ulceration and diabetes mellitus.
4. Additional bronchodilators
Anticholinergic drugs have a different mechanism of action to B-2-agonists and provide additional bronchodilatation in acute asthma. They should not be used alone, but may be used combination or alternating with the latter, either by nebulisation or in high dose from an MDI attached to a spacer. Their use is not associated with significant side-effects and is preferred to other bronchodilators. They should be used in all patients with severe episodes that require hospitalisation and who fail to improve on the standard regimen, as well as in those intolerant of high doses of B-2-agonists. The usual dose is 0.5 mg ipratropium bromide nebuliser solution 4-hourly or 2 puffs from an MDI repeated to a total of 20 puffs every 4 hours. It may be discontinued when it is clear that the patient is responding.
Intravenous theophylline is a significantly less effective bronchodilator than B-2-agonists and ipratropium bromide. Serious limitations to its use include: (I) a high incidence of acute nausea, vomiting and other side effects when administered rapidly; (ii) serious side-effects if a patient has previously been on long-acting slow-release theophyllines and has therefore been rendered acutely toxic; (iii) the fact that additional benefit beyond that obtained with nebulized B-2-agonist and steroid alone has not been clearly demonstrated; and (iv) the fact that standard recommended doses for intravenous infusions of theophylline are unreliable given the large number of factors that influence its metabolism. Monitoring blood levels is desirable if not essential. Lower doses are required in patients with liver disease or heart failure and in those taking cimetidine, ciprofloxacin, erythromycin and most other macrolide antibiotics. Higher doses are required in smokers. Although the unit cost of aminophylline is lower than for B-2-agonists and ipratropium bromide, this is offset by the additional cost of needles, syringes, infusion sets, blood level monitoring and treatment of complications.
The dose regimen for aminophylline is as follows:
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(i) loading dose 6 mg/kg over 30 minutes. (this must be withheld, or the dose must be halved in patients on oral theophyllines);
(ii) average maintenance dose: 0.6 mg/kg/h = approximately 1000 mg/24 h (see (v) and (vi) for dosage adjustments);
(iii) never use more than 1000 mg/d without monitoring blood levels;
(iv) individual clearance in normal adults varies widely, i.e. individual dosages vary from 300 to 3000 mg/d;
(v) increase dose by one-third in patients with congestive cardiac failure, the elderly, patients with liver disease and patients on most macrolide antibiotics, ciproflaxacin or cimetidine.
B-2-agonists administered intramuscularly, subcutaneously or by continuous intravenous infusion have not been shown to be superior to inhaled B-2-agonists and are associated with more side-effects. They may be considered in severe attacks where nebulised B-2-agonists fail to achieve a sustained response. A loading dose, followed by constant infusion, is recommended, the rate of which is adjusted according to improvement in the PEF. Side-effects include tachycardia and hypokalaemia. Serum potassium should be measured at least daily. The infusion should be stopped when the patient shows sustained improvent (usually not be continued longer than 24 hours).
Usual doses are: salbutamol 0.5 mg IMI or subcutaneously, or 0.25 mg slowly intravenously. This may be repeated 4-hourly as required or once followed by an infusion of 3-20 ug/min of a solution 5 mg/5ml diluted in 500 ml dextrose water or normal saline.
Adrenalin injected subcutaneously is indicated for acute treatment of anaphylaxis, angio-edema and occasionally, for asthma when severe exacerbations are not relieved by inhaled B-2-agonists and ipratropium bromide. Being less B-2-agonist specific, it has several side-effects, and its advantage over B-2 specific agonists is doubtful.
The following drugs do not form part of the routine management of exacerbations:
- Antibiotics are indicated only for patients with fever and purulent sputum (due to polymorphs, not eosinophils) that suggest bacterial infection.
- Inhaled mucolytics should not be used as they worsen cough and airflow obstruction.
- Sedation is contraindicated because of its respiratory depressant effect.
- Antihistamines have no role in the treatment of exacerbations.
- Percussive chest physiotherapy is not beneficial and may actually provoke bronchospasm and worsen the attack.
- Hydration with large volumes of fluids is unnecessary in adults and older children
Periodic assessments
A nurse or doctor should remain with the patient for at least 15 minutes after admission and until improvement is observed. The following should be monitored at frequent intervals: PEF should be measured at 15-30 minutes after starting treatment, and at 2 hours and thereafter, before and after each treatment with nebulised B-2-agonist (at least 4 times daily) throughout the admission. Other clinical features for assessing severity of asthma (Table 1) should be measured hourly in severe cases, 4-hourly in those showing a satisfactory response. Blood gas measurements should be repeated only if the patientпїЅs condition appears to be deteriorating, of if it fails to improve after 2 or 4 hours in patients in whom the initial PaO2 was low and initial PaCO2 was normal raised. Anxiety should be relieved by verbal reassurance and care. Where treatments have similar efficacy and safety, non-invasive and non-painful methods should be used. Thus, inhaled or oral B-2-agonists and corticosteroids are preferred over arterial blood gas measurements. Routine chest radiography is not necessary, but should be performed if pneumonthorax, atelectasis, pneumonia or pulmonary oedema is suspected, or if the patient fails to respond promptly to treatment. Plasma electrolytes and urea values should be measured during prolonged attacks and when the development of hypokalaemia is possible (e.g. during systemic B-2-agonist use). The need for other investigations e.g. blood counts, electrocardiography, should be judged on an individual basis.
Criteria for admission to hospital (longer stay).
Both medical and social factors must be considered. When in doubt, admit. Factors suggesting the need for hospitalisation include: (I) inadequate response to therapy within 1-2 hours of treatment. (Fig.3 (Available on request)); (ii) persistent severe airflow limitation (PEF less than 50% of predicted or personal best); (iii) past history of severe asthma, particularly if hospitalisation was required; (iv) recurrence after recent exacerbation; (v) presence of high risk-factors; (vi) prolonged symptoms before current emergency room visit; (vii) any of the following social and personal factors: inadequate access to medical care and medication, difficult home conditions, difficulty obtaining transport to hospital in event of further deterioration, difficulty following asthma management plan. An overnight stay is advised when the patients are seen in the afternoon or evening rather than earlier in the day.
Criteria for admission to intensive care unit
Patients are considered in need of intensive care when either of the following is present: (I) little response to initial therapy in clinic or hospital; or (ii) signs of imminent respiratory arrest, such as cyanosis, exhaustion, drowsiness, confusion, silent chest, bradycardia, rising PaCO2 and persistent acidosis. (Table II).
It is preferable to err on the side of caution. Not all patients admitted to the intensive care unit need intubation and ventilation. Although it is desirable to avoid ventilation, delaying tracheal intubation until the patient suffers respiratory and/or cardiac arrest is a serious error of judgement. Intubation is indicated where there is progressive deterioration in clinical features despite optimal therapy, the patient is exhausted and/or acidotic and/or the PaCO2 continues to rise. Intubation of the distressed asthmatic requires considerable skill. It should be unhurried and performed by the most experienced person available.
Management prior to discharge
Early discharge after moderate episodes of acute asthma is indicated where, as defined in Fig 3 (Available on request), exacerbations respond rapidly to initial treatment, provided that the patientпїЅs PEF or FEV1 has returned to 75% or more of predicted or personal best, physical examination is normal and the patient feels both undistressed and recovered. Patients admitted for severe attacks should not be discharged until their symptoms have cleared, lung function tests stabilised or returned to their usual best (PEF >75%, diurnal variability <25%) and nocturnal symptoms have been alleviated. Diurnal variability is calculated as follows: highest PEF minus lowest PEF in each 24-hour period, divided by highest PEF and multiplied by 100.
All patients considered ready for discharge require the following:
(i) regular inhaled B-2-agonists (4-hourly). Change from nebulizer to standard MDI 24-48 hours before discharge. Check patientsпїЅ inhaler technique;
(ii) to commence or continue inhaled anti-inflammatory drug, usually a corticosteroid;
(iii) to continue the booster course of oral corticosteroid for at least a week after symptoms of asthma have disappeared, or until the follow up visit;
(iv) an appointment to visit the family practitioner or usual physician within days or, at most, 2 weeks, and a discharge note stating details of treatment and discharge PEF rate;
(v) to have ready access to emergency medical care should a recurrence occur within days;
(vi) a self-management plan with instructions about recognising deterioration, self-adjustment to treatment, early notification of their doctor and self referral for emergency treatment. Some patients may benefit from provision of a peak flow meter to guide their self-management plan; and
(vii) a review of the circumstances leading to this admission, and sound advice in this regard. Was there an avoidable precipitating cause e.g. upper respiratory tract infection or inhaled agent in home or workplace?
Give advice on trigger factors. What was the pattern of deterioration: acute and sudden or with recognisable slow deterioration? Did the patient (and/or relatives) react appropriately? Was the patient compliant with regular treatment? Was medical management in the emergency room and hospital appropriate? Review the asthma action plan to ensure that doses of regular medications are appropriate.
These guidelines are modelled on the “The International Consensus Report on Diagnosis and Treatment of Asthma” published by the US Department of Health and Human Services (publication number 92-3091, June 1992),
Guidelines for management of asthma in adults: I Chronic persistent asthma (BMJ 1990; 301: 651-653) and
Acute severe asthma in adults and children published by the British Thoracic Society (Thorax 1993; 48: Supplement S12-S24).
They have previously been published in S Afr Med J 1992; 81: 319-322 and
S Afr Med J 1994; 84: 332-338.
Permission by the editors and publishers of these reports is gratefully acknowledged.