Asthma exacerbations · 5: Assessment and management of severe asthma in adults in hospital
Free- Sarah Aldington1,
- Richard Beasley1,2
- 1Medical Research Institute of New Zealand, Wellington, New Zealand
- 2Wellington Hospital, Capital and Coast District Health Board, Wellington, New Zealand
- Correspondence to:
Professor Richard Beasley
Medical Research Institute of New Zealand, P O Box 10055, Wellington, New Zealand; richard.beasley{at}mrinz.ac.nz
Abstract
It is difficult to understand why there is such a huge discrepancy between the management of severe asthma recommended by evidence-based guidelines and that observed in clinical practice. The recommendations are relatively straightforward and have been widely promoted both in guidelines and reviews. Specialist physicians need to be more proactive in their implementation of such guidelines through the use of locally derived protocols and assessment sheets, reinforced by audit. The common occurrence of severe asthma and its considerable burden to the community would support such an approach.
- CPAP, continuous positive airway pressure
- FEV1, forced expiratory volume in 1 s
- HDU, high dependency unit
- ICU, intensive care unit
- NIPPV, non-invasive positive pressure ventilation
- Pao2, Paco2, arterial oxygen and carbon dioxide tension
- PEF, peak expiratory flow
- PVCD, paradoxical vocal cord dysfunction
- Spo2, oxygen saturation
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- CPAP, continuous positive airway pressure
- FEV1, forced expiratory volume in 1 s
- HDU, high dependency unit
- ICU, intensive care unit
- NIPPV, non-invasive positive pressure ventilation
- Pao2, Paco2, arterial oxygen and carbon dioxide tension
- PEF, peak expiratory flow
- PVCD, paradoxical vocal cord dysfunction
- Spo2, oxygen saturation
Over the last two decades, British guidelines on the management of asthma have provided evidence-based recommendations for the assessment and management of severe asthma in hospitals.1–3 Practical assessment and management algorithms have been provided, supported by clear advice regarding their implementation. Despite their availability and widespread promotion, repeated audits have indicated that there is a major discrepancy between the standard of current medical management of severe asthma in hospitals and that recommended in the guidelines.4–6 Common problems include inadequate assessment and recognition of severity, confusion over the use and interpretation of investigations, insufficient use of systemic steroids, over-reliance on bronchodilators, delayed specialist or intensivist referral and poor follow-up arrangements including communication with the general practitioner [GP] [table 1].
Table 1
Hospital management of severe asthma: the problems
Recognition of these problems provides a good basis for determining priorities for the hospital care of patients with severe asthma [table 2]. In this review we focus on these issues and the clinical approaches that might be used to improve the management of severe asthma in adults in hospital. We also highlight the use of assessment sheets and treatment protocols in the emergency department to illustrate how the guidelines can be implemented in a simple and practical manner. The review also raises issues of clinical uncertainty that need to be considered in updated versions of the guidelines and where further research is required.
Table 2
Hospital management of severe asthma: the priorities
HISTORY
A brief history can be obtained while the patient is being initially examined as part of the clinical assessment. The priority is to identify quickly the patient at increased risk of serious morbidity and mortality from asthma, and this can be achieved by asking a few questions to determine the background chronic asthma severity and the severity of the acute attack [table 3]. Among the markers of an increased baseline risk of death that have been identified, a hospital admission in the previous 12 months is the most reliable and easily ascertained, with the occurrence of multiple hospital admissions for asthma signifying a greatly increased risk.7–9 The amount of β-agonist regularly used by the patient is also informative, based on epidemiological evidence that increasing use is associated with a progressively greater likelihood of a hospital admission and/or risk of death.10 For example, the Saskatchewan study reported that the risk of death increased markedly with the use of more than two β-agonist inhalers per month.10 The factor which identifies patients at greatest long-term risk of death is a previous life-threatening attack [ever], which is most easily documented by obtaining a history of a previous intensive care unit [ICU] admission for asthma.11
Table 3
Markers of risk of an adverse outcome in asthma
The amount of inhaled β-agonist self-administered during the exacerbation is a good marker of the severity of the acute attack and risk of a poor outcome. It also gives the attending doctor an indication of the likelihood of a response to further inhaled β-agonist treatment and requirement for systemic steroid treatment. In a study of adult patients admitted to hospital with severe asthma,12 about half had used at least 30 doses from their β-agonist inhaler in the 24 h before presentation and about 20% had used over 60 doses. Most patients who had access to both an inhaler and nebuliser had used the nebuliser more than four times, as well as at least 20 doses of their inhaler during the 24 h period before admission. The likely poor response to further inhaled bronchodilator and the requirement for hospital admission and systemic steroid treatment could be predicted from such heavy prior β-agonist use.
For those patients who have monitored their peak flow during the attack, marked variability in peak flow with falls of >50% from baseline is a marker of risk of sudden death.13,14
The perceived speed of onset of the attack is also informative for recognising asthmatic patients with “precipitate attacks” who are likely to present with more severe asthma but have a greater improvement with treatment.15–17 Overall precipitate attacks are uncommon, representing around one in eight presentations at the emergency department when defined as an onset of symptoms within 3 h of presentation. The more common presentation is that of a gradual deterioration over many days before a more rapid worsening just before presentation.
Additional history will be required, including markers of poor long-term control [such as nocturnal wakening] and precipitating factors, of which viral upper respiratory tract infections are most common. In cases of precipitate asthma, allergen exposure, use of non-steroidal anti-inflammatory drugs and psychological stress are important factors to consider.15–17 In addition to documentation of the routine medications [including compliance with inhaled corticosteroid therapy], consideration of other issues such as continuity of primary care, adverse behavioural or psychosocial problems and the presence of comorbid conditions is required.18
It is also informative to ask the patient to describe the sequence of events in the 24 h period before admission to establish if there was a significant delay in the recognition of the severity of the attack and whether earlier medical review should have occurred. This provides the opportunity to discuss “what should have happened in this attack” and recommend what steps might be taken to ensure a better outcome in the next attack. This advice may also serve as the basis for implementing a self-assessment and management plan prior to discharge.
Consideration should also be given to other disorders which may mimic or coexist with asthma. Particular consideration should be given to paradoxical vocal cord dysfunction [PVCD],19,20 which is normally recognised by patients attending the emergency room frequently with poorly reproducible lung function measurements and predominant wheezing during both expiration and inspiration originating from the larynx rather than the chest. Other distinctive features include a predominance in women, a background of psychological or psychiatric problems, and a lack of response to standard asthma management. Careful elicitation of symptoms and signs of PVCD at presentation may be helpful in its subsequent investigation, which is based on laryngoscopy and flow-volume loops. This is important not only because PVCD is amenable to treatment, but also because it can reduce the risk of substantial morbidity with intensive treatment including long-term oral corticosteroids.
CLINICAL EXAMINATION
The priority of the clinical examination is to confirm the diagnosis of asthma quickly and to assess its severity. The general appearance of the patient, including difficulty in talking, respiratory rate and heart rate form the basis of the clinical assessment of severity.21,22 Increasing pulse rate has a close correlation with worsening asthma severity, and it is incorrect to assume that the tachycardia is due to β-agonist treatment. Studies of the response to high-dose β-agonist treatment in severe asthma have shown that the heart rate falls in association with the bronchodilator response.21,23
While it is generally well recognised that some patients may have a poor perception of the severity of their asthma,24,25 it is less well appreciated that such patients may also appear deceptively well, despite the presence of severe airflow obstruction.26 These factors contribute both to delay in seeking medical help by the patient and a tendency for the doctor not to appreciate the severity when the patient does present. This underlies the importance of lung function measurements in severe asthma, as well as eliciting other clinical signs such as the difficulty a patient may have in talking,21 blood pressure paradox, accessory muscle use and tracheal tug. In acute severe asthma, the marked hyperinflation and associated greater inspiratory muscle effort is responsible for the patient’s perception that the difficulty in breathing is predominantly inspiratory rather than expiratory.27 The inspiratory muscle work may increase up to tenfold in patients with severe asthma in whom the FEV1 is 15 mm Hg] should alert the doctor to the presence of a severe attack.21,29 Although difficulties in their interpretation and wide observer variability have led to a reduced emphasis on their use, these clinical examination features are informative when carefully elicited, and clinicians are encouraged to develop and maintain these clinical examination skills. Other clinical signs which indicate life-threatening asthma include patients assuming the upright position [or an inability to lie supine], cyanosis and sweating.21 Confusion or a reduced level of consciousness may be a premorbid sign, although many patients remain fully conscious until immediately before a fatal cardiac arrest.
The clinical severity markers that should alert the assessing doctor to the presence of a life-threatening attack are outlined in table 4. While these criteria appear practical and simple to apply, they have inherent limitations.26 First, the clinical symptoms and signs of severe asthma often do not correlate with the severity of physiological impairment and, as a result, their absence is not necessarily reassuring. Another limitation is that the components do not develop simultaneously or at unique levels of impairment. It is recommended that it is wise to base management on the “worst” abnormality and not be reassured because another feature does not fall within the definition of severe.18 In this way, some patients may be admitted unnecessarily or be overtreated, but some “preventable” deaths from asthma can be avoided.
Table 4
Levels of severity of acute asthma exacerbations
Lung function tests
Lung function tests are the basis for assessment of the severity of the asthmatic attack [table 4].3,18,22 Preferably, this should be undertaken by spirometry with measurement of the forced expiratory volume in 1 s [FEV1] expressed as a percentage of predicted normal values. The National Health and Nutrition Examination Survey [NHANES] reference prediction equations should be used rather than the traditional European Coal and Steel normal values which are now acknowledged to be out of date and underestimate normal reference values by about 15%.30
Measurement of the peak expiratory flow [PEF], with values expressed as predicted normal values, represents an alternative if spirometry is not available. The normal reference values sourced from the Nunn and Gregg nomogram are recommended for the calculation of “percent predicted” PEF values.31 Contrary to current dogma, the PEF and FEV1 are not equivalent when expressed as a percentage of predicted values, with the FEV1 being on average 5–10 percentage points lower than the PEF [ie, FEV1 of 30% predicted is equivalent to PEF of 35–40%].32,33 There is also marked intra-patient variability in the relationship, with 95% confidence intervals of around 50 percentage points. This means that major differences in the classification of asthma severity may occur [and the treatment recommended on the basis of this classification], depending on the lung function measurement used. This caution particularly applies to the assessment and management of life-threatening asthma in which FEV1 values are 4–10% lower than the PEF across the FEV1 range of 20–33% predicted.34,35
While recognising the poor correlation between clinical signs and physiological measures, an FEV1 of 5.3 kPa [40 mm Hg], a quiet chest with the absence of audible wheezing, respiratory rate >30/min or pulsus paradoxus >20 mm Hg.21,36,37
Importantly, the magnitude of the improvement in lung function following initial bronchodilator treatment represents the most informative measure of severity of the acute episode and likely requirement for hospital admission.38 As a result, severity may be best defined in terms of outcome rather than the patient’s initial presentation.26
If one accepts that the FEV1 is the “gold standard” method of assessing airflow obstruction in asthma, and that lung function measurements are essential in the assessment of asthma, a strong case can be made for the provision of spirometers in all hospital emergency departments. This case is further strengthened when one considers the use of spirometry in the assessment of other respiratory disorders and the costs and relative benefits of other medical equipment used in emergency departments. Peak flow measurements are preferred for monitoring lung function following admission to the ward.
While the measurement of the magnitude of hyperinflation is not indicated in the acute setting, it is informative to be aware that, in severe asthma, the residual volume can approach 400% and functional residual volume can be double the expected values.37
Oxygen assessment and other tests
Measurement of oxygen saturation by pulse oximetry should be undertaken in all patients with severe asthma presenting to hospital. In the absence of oxygen therapy, arterial desaturation and hypercarbia occur concurrently and normally only develop in life-threatening asthma.37 As a result, pulse oximetry is a suitable means for the routine assessment of ventilatory status. Analysis of arterial blood gases can be selectively reserved for those patients with oxygen saturations on room air of 2.5 mg every 20 min.53 This regime has equivalent bronchodilator efficacy to 7.5 mg salbutamol every 20 min in acute severe asthma. If there is an inadequate response to this regime, the best option is to proceed to continuous β-agonist nebulisation.23,54
Metered dose inhalers with a holding chamber [spacer] produce outcomes that are at least equivalent to nebuliser therapy in severe asthma.55–57 This finding includes those with life-threatening asthma, with an FEV1 50–60% predicted, or if clinical features of severe asthma persist, admission is recommended. Patients may also require admission if, despite achieving an FEV1 >60%, there are other concerns, as outlined in table 6.3 Depending on resources, admission to a respiratory ward is preferable as this is likely to lead to a higher standard of care and better outcome than admission to a general medical ward.84
Table 6
Criteria for admission
A doctor and/or nurse should remain with the patient after initial treatment has started, or at least until clear improvement is seen. The patient should be assessed regularly, with measurement of lung function and heart rate. The frequency of these measurements will be dictated by the response—at least every 15 min initially. Once improvement has occurred, a suitable regimen would be to monitor these measurements before and after bronchodilator treatment. Patients who are stable can be transferred to a medical ward where oxygen can be continued if hypoxic and nebulised β-agonists given every 2–4 h. There is no major advantage in continuing inhaled ipratropium bromide treatment beyond the initial 12–24 h period.85
Oral steroids should be continued throughout the admission. A single morning dose of steroid may not adequately protect the circadian narrowing of the airways experienced at night. The peak effect of oral steroids occurs at around 9 h and then declines and, as a result, may not provide sufficient effect throughout the 24 h dosing interval.86 The clinical significance of this time course of effect is suggested by a small study in which a small dose of prednisolone given at 15:00 hours was shown to be more effective in protecting against nocturnal bronchoconstriction than an 08:00 or 20:00 hours dosing regime.87 To overcome this problem, the preferred dosing regime in hospital is twice daily, in contrast to the once morning regime routinely used as an outpatient. As discussed, the effective daily dose of oral prednisolone is between 30 and 50 mg.88
On average, it takes 7–10 days for symptoms and lung function to stabilise after an asthma exacerbation and, for this reason, a 10–14 day course is usually recommended. Unless the patient is on maintenance oral steroids, tapering the dose at the end of the course is unnecessary. Studies comparing abrupt cessation with a tapering regime found no difference in lung function or relapse rate between the two groups.89,90 Suppression of the hypothalamic pituitary axis is not clinically significant after a short course in a patient who is not on maintenance steroids.
Treatment with inhaled corticosteroids should be continued throughout the admission as there is evidence that it may have efficacy in this situation79,80 and to reinforce the importance of this long-term treatment to patients.
The prescription of sedatives has been associated with sudden death due to their effect in reducing respiratory drive and alertness, and they are therefore contraindicated outside the ICU.13,14 Percussive physiotherapy is likely to distress a severely ill asthmatic patient and is contraindicated in the initial stages, although relaxation techniques to achieve control over the rate, depth and pattern of breathing may be helpful in the recovery phase.
Antibiotics should not be routinely prescribed as bacterial infections seldom provoke exacerbations [in contrast to viral respiratory tract infections], and their routine prescription does not influence outcome in exacerbations of asthma.91 Consideration may need to be given to use of a macrolide if chronic Mycoplasma or Chlamydia pneumoniae infection are suspected in chronic unstable disease; however, data to support this approach are not yet conclusive.92
It is difficult to determine the optimal duration of hospital stay for an admission for severe asthma. Because of the widespread under-resourcing of medical inpatient beds, there is often considerable management pressure to discharge patients early. However, in the case of asthma, this approach is not without risk, not least because there is an increased risk of early relapse and readmission in the two to three months after admission.93 Perhaps the best predictor of outcome is the PEF variability in the 24 h before discharge, for which it has been shown that a diurnal variation in PEF of >20% is associated with an increased risk of further severe attacks requiring repeat hospital admission.94
One approach which facilitates early discharge is the use of nebulised β-agonist treatment according to an “as required” regime rather than a regular 4-hourly regime from 24 h after hospital admission.95 Implementation of this “as required” regime has similar efficacy but results in an average reduction in the length of hospital stay of about 1 day. This outcome is achieved with about half the total dose of β-agonist administered, a reduced incidence of side effects and a strong patient preference for this regime. At least 24 h before scheduled discharge, the patient should be changed from nebulised to their routine aerosol or dry powdered metered dose inhaler to ensure that clinical stability is maintained on this lower dose of β-agonist.
As improvement is achieved, the emphasis shifts to investigation of the causes and circumstances of the severe attack, and arrangements are made for management following discharge, long term treatment, the institution of a self-management plan and appropriate follow-up arrangements.
DISCHARGE ARRANGEMENTS
Whether the discharge occurs from the emergency department or hospital ward, it is crucial that doctors address the problems that may have led to the hospital admission. Patients admitted to hospital with asthma and those who make frequent attendances at the emergency department are recognised as a particularly high-risk group of patients who have poor self-management skills and often have inadequate medical follow-up in the community. For this reason, doctors should ensure that patients are prescribed regular inhaled corticosteroids and that their inhaler technique is checked before discharge. It is also worthwhile to provide simple advice on what to do if their asthma worsens again. This can be achieved by giving patients a peak flow meter with instructions concerning the level at which to seek medical care either from their GP or, if necessary, the emergency department. Doctors are also encouraged to prescribe a course of oral steroids, based on the evidence that in this situation it greatly improves outcome with a fourfold reduction in relapse rate in the following week.96 This recent systematic review reported that about 15 patients need to be treated to prevent relapse requiring medical care after discharge from the emergency department with an exacerbation of asthma.96
Written communication with the GP via letter or email concerning the details of the ED attendance and/or hospital admission is essential to help address the problem of discontinuity of care. Alternatively, it may be advisable to phone if there is a delay in letters being typed and sent out, due to the high rate of relapse in the first week following discharge. Arrangements need to be made for medical follow-up both with the GP and with the respiratory specialist in the case of life-threatening asthma. An open access self-admission service should be considered in patients who have experienced a life-threatening or precipitate attack. The advantages of such a service, which may require prior arrangement with the ambulance service, have been shown.97
ASSESSMENT SHEETS AND TREATMENT PROTOCOLS
One approach which has been used to facilitate clinical practice in accordance with guidelines is the implementation of assessment sheets and treatment protocols.98,99,100,101,102,103 When used in the emergency department, they have been shown to identify rapidly individuals at risk of an adverse outcome, ensure a high standard of management, facilitate the appropriate referral to respiratory wards and medical ICU and improve outcomes such as length of stay and number of subsequent return visits. Treatment protocols are traditionally limited to algorithm-based flow charts, but the addition of an assessment sheet facilitates their implementation. This is particularly the case with severe asthma in which management is determined by asthma severity and in which doctors seem to have major difficulties in following this approach.
A guideline-based asthma assessment and associated treatment algorithm is shown in figs 1 and 2. The assessment sheet is designed to encourage a quick focused history to identify baseline and acute risk, an objective assessment of asthma severity, and repeat clinical examination and measures of FEV1. The response to treatment can thus be assessed and a decision made on whether the patient requires admission or can be discharged. In this case, a structured approach is provided to address issues relating to long-term care and advice on when the patient should present again if their asthma deteriorates further.
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Figure 1
Asthma Assessment Sheet currently in use in the Wellington Hospital Emergency Department, Wellington, New Zealand. FEV1, forced expiratory volume in 1 s; ICU, intensive care unit; VC, vital capacity; Paco2, arterial carbon dioxide tension; Pao2, arterial oxygen tension; PEF, peak expiratory flow.
Key points
The management of asthma in the emergency department can be improved through the use of simple assessment and treatment protocols.
Assessment of asthma severity should be based primarily on the measurement of FEV1, expressed as the percentage of normal predicted values.
For most patients, initial treatment with high-flow oxygen, nebulised β-agonist and oral corticosteroids is sufficient.
Currently available evidence does not support the routine use of intravenous theophylline or intravenous β-agonist treatment in acute asthma; magnesium is the preferred intravenous bronchodilator in life-threatening asthma.
Patients with any feature of a severe attack persisting after initial treatment should be admitted; patient circumstances should also be considered.
For patients who are discharged, long-term management should be reviewed and medical follow-up arranged.
The algorithm recommended in the British guidelines, based on peak flow, is shown in fig 3. Modification of the current protocols and assessment sheets for use in general practice is encouraged, where similar problems in the assessment and management of severe asthma may also be encountered.104
CONCLUSIONS
It is difficult to understand why there is such a huge discrepancy between the management of severe asthma recommended by evidence-based guidelines and that observed in clinical practice. The recommendations are relatively straightforward and have been widely promoted both in guidelines1–3 and reviews.18,22,26,105 It is likely that the problems are related in part to the inexperience of the junior medical staff who are commonly delegated responsibility for the hospital care of patients with severe asthma, and to inadequate senior medical supervision. Specialist physicians need to be more proactive in their implementation of such guidelines through the use of locally derived protocols and assessment sheets, reinforced by audit.
REFERENCES
- ↵
British Thoracic Society. Guidelines for management of asthma in adults: II – Acute severe asthma. BMJ1990;301:797–800.
British Thoracic Society. Guidelines on the management of asthma. Thorax1993;48 [Suppl 1] :S1–24.
- ↵
British Thoracic Society/Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. Thorax. 2003;58[Suppl I].
- ↵
Pearson MG, Ryland I, Harrison BDW. Comparison of the process of care of acute severe asthma in adults admitted to hospital before and 1 yr after the publication of national guidelines. Respir Med1996;90:539–45.
Ulahannan T, Hardern RD, Hamer DW. Do accident and emergency senior house officers know the British guidelines on the management of acute asthma? Postgrad Med J1996;72:162–3.
- ↵
Hart SR, Davidson AC. Acute adult asthma: assessment of severity and management and comparison with British Thoracic Society Guidelines. Respir Med1999;93:8–10.
- ↵
Crane J, Pearce N, Burgess C, et al. Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma. Int J Epidemiol1992;21:737–44.
Rea HH, Scragg R, Jackson R, et al. A case-control study of deaths from asthma. Thorax1986;41:833–9.
- ↵
Turner MO, Noertjojo K, Vedal S, et al. Risk factors for near-fatal asthma: a case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med1998;157:1804–9.
- ↵
Spitzer WO, Suissa S, Ernst P, et al. The use of β-agonists and the risk of death and near death from asthma. N Engl J Med1992;326:501–6.
- ↵
Marquette CH, Saulnier F, Leroy O, et al. Long-term prognosis of near-fatal asthma: a 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis1992;148:76–81.
- ↵
Windom HH, Burgess CD, Crane J, et al. The self-administration of inhaled beta agonist drugs during severe asthma. NZ Med J1990;103:205–7.
- ↵
Hetzel MR, Clark TJH, Branthwaite MA. Asthma: analysis of sudden deaths and ventilatory arrests in hospital. BMJ1977;1:808–11.
- ↵
Bateman JAM, Clark SW. Sudden death in asthma. Thorax1979;34:40–4.
- ↵
Rodrigo GJ, Rodrigo C. Rapid-onset asthma attack: a prospective cohort study about characteristics and response to emergency department treatment. Chest2000;118:1547–52.
Barr RG, Woodruff PG, Clark S, et al. Sudden-onset asthma exacerbations: clinical features, response to therapy, and 2-week follow-up. Eur Respir J2000;15:266–73.
- ↵
Salmeron S, Liard R, Elkharrat D, et al. Asthma severity and adequacy of management in accident and emergency departments in France: a prospective study. Lancet2001;25:629–35.
- ↵
Harrison BDW. Acute severe asthma. In: Gibson GJ, Geddes DM, Costabel U, et al eds. Respiratory medicine. 3rd ed. Volume 2. Oxford: Elsevier Science, 2003:1378–95.
- ↵
Goldman J, Muers U. Vocal cord dysfunction and wheezing. Thorax1991;46:401–4.
- ↵
Christopher KL, Wood RP, Eckert RC, et al. Vocal cord dysfunction presenting as asthma. N Engl J Med1983;308:1566–70.
- ↵
Neville E, Gribbin H, Harrison BDW. Acute severe asthma. Respir Med1991;85:463–74.
- ↵
Harrison BDW. Guidelines for management of acute asthma in adults. In: O’Byrn P, Thompson NC, eds. Manual of asthma management. London: WB Saunders & Co, 1995:557–76.
- ↵
Lin RY, Sauter D, Newman T, et al. Continuous versus intermittent albuterol nebulization in the treatment of acute asthma. Ann Emerg Med1993;22:1847–53.
- ↵
Rubinfeld AR, Pain MC. Perceptions of asthma. Lancet1976;i:882–4.
- ↵
Kendrick AH, Higgs CM, Whitfield MJ, et al. Accuracy of perception of the severity of asthma: patients treated in general practice. BMJ1993;307:422–4.
- ↵
McFadden ER Jr. Acute severe asthma. Am J Respir Crit Care Med2003;168:740–59.
- ↵
Morris MJ. Asthma – expiratory dyspnoea? BMJ1981;283:838–9.
- ↵
Martin JG, Shore SA, Engel LA. Mechanical load and inspiratory muscle action during induced asthma. Am Rev Respir Dis1983;128:455–60.
- ↵
Rebuck AS, Read J. Assessment and management of severe asthma. Am J Med1971;51:788–98.
- ↵
Roca J, Burgos F, Sunyer J, et al. Reference values for fixed spirometry. Eur Respir J1998;11:1354–62.
- ↵
Nunn AJ, Gregg I. New regression equations for predicting peak expiratory flow in adults. BMJ1989;298:1068–70.
- ↵
Sawyer G, Miles J, Lewis S, et al. Classification of asthma severity: should the international guidelines be changed? Clin Exp Allergy1998;28:1565–70.
- ↵
Llewellin P, Sawyer G, Lewis S, et al. The relationship between FEV1 and PEF in the assessment of the severity of airways obstruction. Respirology2002;7:333–7.
- ↵
Nowak RM, Tomlonorich MC, Sarker DD, et al. Arterial blood gases and pulmonary function testing in acute bronchial asthma: predicting patient outcomes. JAMA1983;249:2043–6.
- ↵
Harrison BDW, Swarbrick EJ. Peak flow percentage in asthma. Lancet1971;ii:492.
- ↵
McFadden ER, Lyons HA. Arterial blood gas tensions in asthma. N Engl J Med1968;278:1027–32.
- ↵
McFadden ER, Kiser R, De Groot WJ. Acute bronchial asthma: relations between clinical and physiologic manifestations. N Engl J Med1973;288:221–5.
- ↵
Kelsen SE, Kelsen DP, Fleegler BF, et al. Emergency room assessment and treatment of patients with acute asthma. Adequacy of the conventional approach. Am J Med1978;64:622–8.
- ↵
Carruthers DM, Harrison BDW. Arterial blood gas analysis or oxygen saturation in the assessment of acute asthma. Thorax1995;50:186–8.
- ↵
Zieverink SE, Harper AP, Holden RW, et al. Emergency room radiography of asthma: an efficacy study. Radiology1982;145:27–9.
- ↵
White CS, Cole RP, Lubetsky HW, et al. Acute asthma: admission chest radiography in hospitalised adult patients. Chest1991;100:14–6.
- ↵
Thomson AJ, Webb DJ, Maxwell SRJ. Oxygen therapy in acute medical care: the potential dangers of hyperoxia need to be recognised. BMJ2002;324:1406–7.
- ↵
Chien JW, Ciufo R, Novak R, et al. Uncontrolled oxygen administration and respiratory failure in acute asthma. Chest2000;117:728–33.
- ↵
Downs JB. Has oxygen administration delayed appropriate respiratory care? Fallacies regarding oxygen therapy. Respir Care2003;48:611–20.
- ↵
Downs JB, Smith RA. Increased inspired oxygen concentration may delay diagnosis and treatment of significant deterioration in pulmonary function. Crit Care Med1999;27:2844–6.
- ↵
Kass JE, Terregino CA. The effect of heliox in acute severe asthma: a randomized controlled trial. Chest1999;116:296–300.
- ↵
Manthous CA, Hall JB, McImed A, et al. Heliox improves pulsus paradoxus and peak expiratory flow in non-intubated patients with severe asthma. Am J Respir Crit Care Med1995;151:310–4.
- ↵
Henderson SO, Acharya P, Kilaghbian T, et al. Use of heliox-driven nebulizer therapy in the treatment of acute asthma. Ann Emerg Med1999;33:141–6.
- ↵
Ho AM, Lee A, Karmakar MJ, et al. Heliox vs air-oxygen mixtures for the treatment of patients with acute asthma: a systematic overview. Chest2003;123:882–90.
- ↵
Rodrigo GJ, Rodrigo C, Pollack CV, et al. Use of helium-oxygen mixtures in the treatment of acute asthma: a systematic review. Chest2003;123:891–6.
- ↵
Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in acute asthmatic attack. Chest2003;123:1018–25.
- ↵
Meduri GU, Cook TR, Turner RE, et al. Non-invasive positive pressure ventilation in status asthmaticus. Chest1996;110:767–74.
- ↵
Emerman CL, Cydulka RK, McFadden ER. Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthma. Chest1999;115:92–6.
- ↵
Shrestha M, Bidadi K, Gourlay S, et al. Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults. Chest1996;110:42–7.
- ↵
Idris AH, McDermott MF, Raucci JC, et al. Emergency department treatment of severe asthma: metered-dose inhaler plus holding chamber is equivalent in effectiveness to nebulizer. Chest1993;103:665–72.
Cates CJ, Bara A, Crilly JA, et al. Holding chambers versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database System Rev2005;[3]:1–58.
- ↵
Colacone A, Afilalo M, Wokove N, et al. The comparison of albuterol administered by metered dose inhaler and holding chamber or wet nebuliser in acute asthma. Chest1993;104:835–41.
- ↵
Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax2005;60:740–6.
- ↵
Fitzgerald JM, Grunfeld A, Pare PD, et al. The clinical efficacy of combination nebulized anticholinergic and adrenergic bronchodilators vs nebulized adrenergic bronchodilator alone in acute asthma. Chest1997;111:311–5.
- ↵
Ind PW, Dixon CMS, Fuller RW, et al. Anticholinergic blockade of beta-blocker induced bronchoconstriction. Am Rev Respir Dis1989;139:1390–4.
- ↵
Beasley R, Burgess C, Holt S. Call for worldwide withdrawal of benzalkonium chloride from nebuliser solutions. J Allergy Clin Immunol2001;107:222–3.
- ↵
Rafferty P, Beasley R, Holgate ST. A comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebuliser solution. Thorax1988;43:446–50.
- ↵
Beasley R, Fishwick D, Miles JF, et al. Preservatives in nebuliser solutions: risks without benefit. Pharmacotherapy1998;18:130–9.
- ↵
Hughes R, Goldkorn A, Masoli M, et al. Use of isotonic nebulised magnesium sulphate as an adjuvant to salbutamol in the treatment of severe asthma in adults: randomised placebo-controlled trial. Lancet2003;361:2114–7.
- ↵
Blitz M, Blitz S, Hughes R, et al. Aerosolized magnesium sulphate for acute asthma: a systematic review. Chest2005;128:337–44.
- ↵
Rudnitsky GS, Eberlein RS, Schoffstall JM, et al. Comparison of intermittent and continuously nebulized albuterol for treatment of asthma in an urban emergency department. Ann Emerg Med1993;22:842–6.
- ↵
Douglas JG, Rafferty P, Fergusson RJ, et al. Nebulised salbutamol without oxygen in severe acute asthma: how effective and how safe? Thorax1985;40:180–3.
- ↵
Salmeron S, Brochard L, Mal H, et al. Nebulised versus intravenous albuterol in hypercapnic acute asthma. Am J Respir Crit Care Med1994;149:1466–70.
Travers A, Jones AP, Kelly K, et al. Intravenous β2-agonists for acute asthma in the emergency department. Cochrane Database Syst Rev2005;[3]:1–45.
- ↵
Swedish Society of Chest Medicine. High dose inhaled versus intravenous salbutamol combined with theophylline in severe acute asthma. Eur Respir J1990;3:163–70.
- ↵
Parameswaran K, Belda J, Rowe BH. Addition of intravenous aminophylline to β2-agonists in adults with acute asthma. Cochrane Database Syst Rev2005;[3]:1–44.
- ↵
Rowe BH, Bretzlaff JA, Bourdon C, et al. Magnesium sulphate for treatment of acute asthma exacerbations in the ED. Cochrane Database Syst Rev2002;[1].
- ↵
Rowe BH, Spooner CH, Ducharme FM, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev2005; [3] :1–37.
- ↵
Manser R, Reid D, Abramson M. Corticosteroids for acute severe asthma in hospitalised patients. Cochrane Database Syst Rev2002;[2]:1–29.
- ↵
Bowler SD, Mitchell CA, Armstrong JG. Corticosteroids in acute severe asthma: effectiveness of low doses. Thorax1992;47:584–7.
- ↵
Rowe BH, Keller JL, Oxman AD. Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Am J Emerg Med1992;10:301–10.
- ↵
Harrison BDW, Stokes RC, Hart GJ, et al. Need for intravenous hydrocortisone in addition to oral prednisolone in patients admitted to hospital with severe asthma without ventilatory failure. Lancet1986;i:181–4.
- ↵
Edmonds ML, Camargo CA Jr, Brenner BE, et al. Inhaled steroids for acute asthma following emergency department discharge. Cochrane Database Syst Rev2005;[3]:1–43.
- ↵
Levy ML, Stevenson C, Maslen T. Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care. Thorax1996;51:1087–92.
- ↵
Rodrigo GJ. Comparison of inhaled fluticasone with intravenous hydrocortisone in the treatment of adult acute asthma. Am J Respir Crit Care Med2005;171:1231–6.
- ↵
Banner AS, Shad RS, Addington WW. Rapid prediction of need for hospitalisation in acute asthma. JAMA1976;235:1337–8.
- ↵
Tuxen D. Intensive care management of severe asthma including assisted ventilation. In: Holgate ST, Boushey HA, Fabbri LM, eds. Difficult asthma. London: Martin Dunitz, 1999:307–31.
- ↵
Corbridge TC, Hall JB. The assessment and management of adults with status asthmaticus. Am J Respir Crit Care Med1995;151:1296–316.
- ↵
Bucknall CE, Robertson C, Moran F, et al. Differences in hospital asthma management. Lancet1988;i:748–50.
- ↵
Brophy C, Ahmed B, Bayston S, et al. How long should Atrovent be given in acute asthma? Thorax1998;53:363–7.
- ↵
Ellul-Micallef R, Johansson SA. Acute dose response studies in bronchial asthma with a new corticosteroid, budesonide. Br J Clin Pharmacol1983;15:419–22.
- ↵
Beam WR, Weiner DE, Martin RJ. Timing of prednisone and alterations of airways inflammation in nocturnal asthma. Am Rev Respir Dis1992;145:1524–30.
- ↵
Webb JR. Dose response of patients to oral corticosteroid treatment during exacerbations of asthma. BMJ1986;292:1045–7.
- ↵
O’Driscoll BR, Kalra S, Wilson M, et al. Double-blind trial of steroid tapering in acute asthma. Lancet1993;341:324–7.
- ↵
Hatton MQF, Vathenen AS, Allen MJ, et al. A comparison of ‘abruptly stopping’ with ‘tailing off’ oral corticosteroids in acute asthma. Respir Med1995;89:101–4.
- ↵
Graham VAL, Milton AF, Knowles GK, et al. Routine antibiotics in hospital management of acute asthma. Lancet1982;i:418–20.
- ↵
Sutherland ER, Martin RJ. Is infection important in the pathogenesis and clinical expression of asthma? In: Johnson SL, Holgate ST, eds. Asthma: critical debates Oxford: Blackwell Science, 2002:69–84.
- ↵
Pearson MG, Ryland I, Harrison BD. National audit of acute severe asthma in adults admitted to hospital. Standards of Care Committee, British Thoracic Society. Qual Health Care1995;4:24–30.
- ↵
Udwadia ZF, Harrison BD. An attempt to determine the optimal duration of hospital stay following a severe attack of asthma. J R Coll Physicians Lond1990;24:112–4.
- ↵
Bradding P, Rushby I, Scullion J, et al. As-required versus regular nebulized salbutamol for the treatment of acute severe asthma. Eur Respir J1999;13:290–4.
- ↵
Rowe BH, Spooner CH, Ducharme FM, et al. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev2005; [3] :1–22.
- ↵
Crompton GK, Grant IWB. Edinburgh emergency asthma admission service. BMJ1975;4:680–2.
- ↵
Emond SD, Woodruff PG, Lee EY, et al. Effect of an emergency department asthma program on acute asthma care. Ann Emerg Med1999;34:321–5.
- ↵
Wrenn K, Rodewald L, Lumb E, et al. The use of structured, complaint-specific patient encounter forms in the emergency department. Ann Emerg Med1993;22:55–62.
- ↵
Town I, Kwong T, Holst P, et al. Use of a management plan for treating asthma in an emergency department. Thorax1990;45:702–6.
- ↵
McFadden ER Jr, Elsanadi N, Dixon L, et al. Protocol therapy for acute asthma: therapeutic benefits and cost savings. Am J Med1995;99:651–61.
- ↵
Goldberg R, Chan L, Haley P, et al. Critical pathway for the emergency department management of acute asthma: effect of resource utilization. Ann Emerg Med1998;31:562–7.
- ↵
Robinson SM, Harrison BD, Lambert MA. Effect of a preprinted form on the management of acute asthma in an accident and emergency department. J Accid Emerg Med1996;13:93–7.
- ↵
Pinnock H, Johnson A, Young P, et al. Are doctors still failing to assess and treat asthma attacks? An audit of the management of acute attacks in a health district. Respir Med1999;93:397–401.
- ↵
McFadden ER Jr, Hejal R. Asthma. Lancet1995;345:1215–20.