The prevalence of asthma in childhood in Australia and New Zealand ranks among the highest in the world.1^–3 Numerous institutions and organisations have developed paediatric guidelines for asthma management.4 5 In many countries, evidence-based national guidelines have been developed and disseminated.6^–11 Australian guidelines6 from the National Asthma Council and New Zealand guidelines7 from the Paediatric Society of New Zealand acknowledge building on British guidelines8 from the British Thoracic Society and the Scottish Intercollegiate Guidelines Network. Although guidelines are often valuable, evidence supporting practice guidelines can be based on expert clinical panels rather than randomised clinical trials (RCTs).12 13 Doctors may not be aware of guidelines, many do not follow guidelines,14^–16 and evidence that practice guidelines improve health outcomes has been mixed.13

A number of management strategies for acute asthma have seen limited implementation or are based on limited or conflicting scientific evidence. These controversial areas of acute asthma management include: use of metered-dose inhalers with spacers (MDISs) versus nebulisers for delivery of β2-agonists6 7 17^–22; use of ipratropium bromide23^–26; the role of intravenous (IV) bronchodilators including salbutamol,5–7 27 ^–37 aminophylline5^–8 33,34 38^–41 and magnesium sulphate.6–8 42 43

Recently, 11 institutions with large paediatric emergency departments (EDs) in Australia and New Zealand, including all tertiary paediatric centres, formed a research collaborative (PREDICT: Paediatric Research in Emergency Departments International Collaborative).44 PREDICT aims to conduct multi-centre collaborative research to address acute severe conditions in which low incidence may hamper other research methodologies.

In this study we set out to establish the current status of clinical practice guidelines (CPGs) for acute childhood asthma and physician practice at PREDICT sites in comparison with national asthma guidelines6 7 to create hypotheses and determine controversies and barriers for future asthma RCTs.

METHODS

This study was undertaken in two parts: (a) a compilation and review of CPGs for acute childhood asthma from PREDICT sites; (b) a standardised survey of senior emergency doctors at PREDICT sites investigating their management of acute childhood asthma. This project was approved as an audit by the ethics committee of the Royal Children’s Hospital, Melbourne, Australia.

Data were collected from the 11 PREDICT EDs, located at all eight tertiary children’s hospitals and three large mixed hospitals in Australia and New Zealand, with a total annual ED census of 350 000.

The survey tool was reviewed by all site representatives to capture local management variation. Some survey questions were presented in the form of brief clinical scenarios followed by multiple-choice drug management responses, and others allowed open responses, with a total of 27 asthma-related items.

Staff surveyed were consultants practicing paediatric emergency medicine or general emergency medicine at PREDICT sites. After two mailings, questionnaires were returned from November 2005 to February 2006. Responses to the questionnaire were anonymous but site coded. Respondents were asked about their college affiliations, gender, years practicing emergency medicine, and professional appointment.

Each site representative was requested to submit a copy of their site’s current CPGs by November 2005.

Definitions of asthma severity in the questionnaire were based on current asthma CPGs at the Royal Children’s Hospital in Melbourne.45

Data were descriptively analysed.

RESULTS

All 11 PREDICT sites participated in the survey. Completed surveys were returned by 78 out of 83 (94%) senior doctors. Forty (51%) were fellows of the Royal Australasian College of Physicians (FRACP), 28 (36%) were fellows of the Australasian College of Emergency Medicine (FACEM), and 10 (13%) were fellows of both colleges. Respondents reported practising in paediatric emergency practice for a mean (SD) of 6.0 (4.8) years (range 1–22). Thirty-nine (50%) were male, and 38 (49%) practiced emergency medicine full time. All PREDICT sites had unique CPGs for asthma management. All sites differentiated mild, moderate, severe and critical asthma with similar but not identical definitions of severity. Management recommendations were generally stated as “recommend” or “consider” in each CPG.

Mild asthma

The guidelines for management of mild asthma were consistent across the 11 sites (fig 1). All reviewed CPGs recommended salbutamol via MDIS and prednisolone orally. The recommended dose of prednisolone was 1–2 mg/kg for 1–5 days. In the questionnaire, 74 (95%) doctors reported using MDIS for salbutamol delivery, and only 41 (53%) reported steroid administration.

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Figure 1 Clinical practice guideline (CPG) recommendations and survey responses for management of mild and moderate asthma at PREDICT sites (CPGs, n = 11; respondents, n = 78). IV, intravenous; MDI, metered-dose inhaler; Neb, nebuliser.

Moderate asthma

All 11 CPGs for moderate asthma recommended use of salbutamol by MDIS and oral prednisolone orally as the steroid of choice. Practice reported by doctors was consistent with this (fig 1). Only three site CPGs recommended ipratropium for moderate asthma. At the two sites that suggested use of ipratropium by MDIS, 93% of doctors surveyed reported its use. Conversely, only 25% of doctors at the remaining sites reported use of ipratropium for moderate asthma.

For a “5-year-old with a mild to moderate asthma exacerbation”, salbutamol via MDIS would have been used in a dose range of 4–12 puffs (100 μg/puff), with 63 (83%) of the 76 doctors who would have used MDIS administering six puffs. Ipratropium for this patient would be administered by MDIS by 40 of the 48 (83%) doctors using ipratropium, with 18 (45%) using two puffs (21 μg/puff) and 21 (53%) using four puffs. Seventy-seven (99%) doctors would have used oral prednisolone as the steroid of choice at a dose of 1–2 mg/kg, with two-thirds (67%) using 1 mg/kg. Sixty-three (81%) doctors said they would “always”, and another 14 (18%) would “often”, prescribe further outpatient doses of corticosteroid for children presenting with mild to moderate asthma. Seventy-seven (99%) doctors would have prescribed oral prednisolone in a dose range of 1–2 mg/kg for 1–7 days without taper, with 58% reporting a preference for 1 mg/kg for 3 days.

Severe asthma

CPG recommendations for management of severe asthma showed greater inter-site variability than those for mild–moderate asthma (fig 2). All sites recommended salbutamol and ipratropium, but delivery methods varied.

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Figure 2 Clinical practice guidelines (CPG) recommendations and survey responses for management of severe and critical asthma at PREDICT sites (CPGs, n = 11; respondents, n = 78). IV, intravenous; MDI, metered-dose inhaler; Neb, nebuliser; salb, salbutamol.

All respondents would have used salbutamol and 64 (82%) would have used ipratropium for severe asthma, with two-thirds using these agents in nebulised form. Seven (64%) site CPGs recommended IV salbutamol for severe asthma, but, for the clinical scenario describing severe asthma, only 27 (35%) doctors would have used IV salbutamol.

Critical asthma

For critical asthma, all site CPGs recommended use of continuous nebulised salbutamol, nebulised ipratropium, IV corticosteroids and IV salbutamol (fig 2). In addition, nine sites (82%) recommended IV aminophylline and five (46%) IV magnesium. Seventy-seven (99%) doctors would administer inhaled salbutamol for the scenario of a “5-year-old with severe to critical asthma”, 62 (79%) by nebulisation and 10 (13%) by MDIS or nebuliser or both. Doses of nebulised salbutamol were 2.5–20 mg, with 52 (71%) doctors using 5 mg. For the initial treatment of such a patient, 68 (88%) would use ipratropium, 60 (77%) nebulised, and eight (11%) via MDIS or nebulised. Nebulised ipratropium dosage was 50–500 μg, although 55 (81%) would have used 250 μg.

All sites recommended nebulised administration of ipratropium, with one site suggesting MDIS as an alternative. Seven sites recommended a dose of 250 μg regardless of age or weight, and three recommended a larger dose (500 μg) for larger children (>20 kg or >6 years). One site recommended 125 μg for children under 5 and 250 μg for older children.

CPGs recommended a variety of different steroid regimens: hydrocortisone (five sites); methylprednisolone (four sites); hydrocortisone or methylprednisolone (one site); and hydrocortisone, methylprednisolone or prednisolone (one site). IV methylprednisolone was recommended at a dose of 1 mg/kg every 4–8 h, with most sites recommending 6-hourly doses. Hydrocortisone was recommended at a dose of 4–5 mg/kg, with most sites recommending 4 mg/kg 4–6 hourly. Steroid use reported by doctors for severe to critical asthma reflected site CPGs: intramuscular (IM)/IV hydrocortisone (58%), IM/IV methylprednisolone (36%), oral prednisolone (4%) and IM/IV dexamethasone (3%).

Dosing regimens for IV salbutamol differed in all but two site CPGs. Overall 68 (87%) of doctors reported use of IV salbutamol for critical asthma. Dosing for IV salbutamol was also highly variable. Thirty-nine different dosing regimens were reported by doctors. Bolus administration followed by continuous infusion was recommended in all CPGs and used by 78% of doctors. Bolus practices were similarly variable for both CPGs and doctors in terms of dosage (range 1.5–15 μg/kg/min), bolus duration (range 1–60 min) and total amount of drug administered (range 10–600 μg/kg). Subsequent continuous infusion rates also varied from 0.5 to 15 μg/kg/min in CPGs and 0.5 to 20 μg/kg/min reported by doctors. The most commonly used bolus and continuous infusion combination used by doctors was 5 μg/kg/min over 60 min followed by continuous infusion at a rate of 1–2 μg/kg/min (13 doctors, 22%). For CPGs, the recommended smallest and largest amount of maximum medication delivered in the first hour of therapy varied by a factor of 12 between sites (from 75 to 900 μg/kg), and that for minimum medication in the first hour varied by a factor of 4.5 (from 65 to 300 μg/kg).

Overall, nine sites and 35 (45%) respondents recommended or reported use of aminophylline for critical asthma. Use by site varied from no doctors to 90% of doctors, with 59% of respondents in agreement with their site’s CPG recommendations. Of 43 doctors providing their preferred regimen for IV aminophylline use in critical asthma, 23 (55%) used a bolus followed by continuous infusion, 17 (41%) used a bolus only, and three (7%) used bolus or bolus and continuous infusion. The most frequently used bolus doses were 9–10 mg/kg administered over 20–60 min at seven of the nine sites using the agent and by 14 (33%) respondents and 5–6 mg/kg administered over 20–60 min by 13 (30%) respondents. Seven sites and 24 (57%) doctors used an infusion rate of 0.9–1.1 mg/kg/h.

Five site CPGs recommended the use of IV magnesium. Three recommended a bolus (50 mg/kg over 20 min) followed by a continuous infusion (30 mg/kg/h), and two sites suggested a bolus only (dose range 25–100 mg/kg over 20 min). Overall, 43 responding doctors (55%) would use magnesium for critical asthma. Forty-nine (96%) of the 51 doctors who answered the question said they would administer a bolus only. A dose of 40–50 mg/kg over 20–60 min was used by 32 (65%) doctors (range 15–75 mg/kg over 10–60 min). At the five sites where CPGs recommended the drug for critical asthma, 46% of respondents reported its use. Conversely, 62% of respondents at the remaining sites reported magnesium use.

DISCUSSION

This is the first study to compare asthma-related CPG recommendations and self-reported patterns of physician practice at major paediatric EDs. All sites located in Australia and New Zealand had unique CPGs for the management of asthma. CPGs and responses of doctors were broadly similar and, in general, consistent with national Australian and New Zealand guidelines.6 7 This was particularly true for the management of moderate asthma, with the near-universal use of salbutamol by MDIS and oral steroids in the ED and at discharge, indicating an increase in these practices compared with prior data from some of the same centres.15 46 Variation in CPGs and in physician practice and divergence from CPGs increased with disease severity.

In contrast with US practice described by Tien et al,18 doctors in our study overwhelmingly used MDIS for mild and moderate asthma, consistent with Australian, New Zealand and British recommendations6^–8 and with scientific evidence17 19 20^–22 indicating outcomes at least equivalent to nebuliser delivery and improved outcomes by some measures. The role of ipratropium bromide has been investigated in a systematic review23 suggesting that multiple doses, administered concurrently with inhaled β2-agonist therapy, improved lung function and decreased hospital admission in children with severe asthma. However, a subsequent RCT in hospitalised patients found no difference in asthma scores.24 Concurring with national guidelines,6 7 no site recommended ipratropium for mild asthma, but all sites recommended it for severe and critical asthma. The role of ipratropium in moderate asthma remains unclear,6 23 25 26 although three sites and 42% of respondents suggested its use for this indication.

We found that all PREDICT CPGs agreed on the use of IV salbutamol for severe and critical asthma. Although a Cochrane review28 of IV β2-agonists including mainly adult studies concluded that there was no evidence to support the parenteral use of these agents in severe asthma, IV salbutamol has been shown to improve a number of outcomes in paediatric RCTs.29 35 In addition, Australian6 and New Zealand7 as well as British8 national guidelines recommend IV salbutamol if there is no response to continuous nebulised salbutamol in severe and critical asthma. The variety of dosing regimens used in CPGs in our study is amplified by the survey responses, with 39 different regimens. The amount of drug delivered in the first hour of treatment varied by a factor of 10 (doctors) to 12 (CPGs). This may reflect the inconsistencies in target populations (severity and setting) and dosing regimens used and debated in the paediatric literature.27 29^–33 35^–37 For example, although both authors are from Australian PREDICT sites, Browne et al29 35 used 15 μg/kg over 10 min without a subsequent infusion in two ED-based salbutamol RCTs, whereas Shann30 31 advocates a much higher loading dose of 300 μg/kg, given as 5 μg/kg/min for 1 h, followed by 1 μg/kg/min. National guidelines in Australia6 recommend 15 μg/kg IV bolus over 10 min followed by 1 μg/kg/min infusion similar to British guidelines,8 whereas in New Zealand7 15 μg/kg over 1–2 min are recommended. The role of IV salbutamol versus other IV bronchodilators is not directly addressed in either of these guidelines, and comparative evidence is limited.33 34

National guidelines in both Australia and New Zealand6 7 recommend paediatric aminophylline use only in a paediatric intensive care unit (ICU), and an Australian national survey of ED asthma care5 excluded aminophylline as controversial and only recommended in the ICU setting. However, the agent is clearly used in the ED setting as second or third line therapy in severely ill asthmatic children. A Cochrane review40 and recent RCTs34 38 39 have shown its efficacy in improving a number of important outcomes.33 Overall, 45% of doctors reported its use for critically asthmatic children, although geographical differences are noted. No respondents reported use of aminophylline in either of the two New South Wales sites, whereas over 60% of respondents reported use at the three Victorian sites. Dosing regimens across most sites recommending aminophylline were similar to corresponding data from a large paediatric RCT38 and to Australian national guidelines (10 mg/kg loading dose, followed by 1.1 mg/kg/h infusion if under 9 years and 0.9 mg/kg/h if 9 years and over).6 In the paediatric section of the UK national guidelines, a loading dose of 5 mg/kg is recommended followed by 1 mg/kg/h regardless of age.8 In contrast with a UK non-ICU consultant survey,41 overall, fewer sites recommended and fewer doctors used IV aminophylline (45%) than IV salbutamol (87%). The one paediatric trial with a good trial design comparing IV salbutamol and IV aminophylline34 found aminophylline to result in a reduced length of stay and a lower intubation rate (4% vs 11%).

A recent meta-analysis43 of the use of IV magnesium sulphate for acute asthma in children found it effective in preventing hospitalisation and in improving short-term pulmonary function tests and clinical symptom scores. National Australian guidelines describe IV magnesium as providing additional benefit in children with severe asthma,6 whereas New Zealand guidelines do not include the agent in paediatric care.7 Our results reflect the conflicting evidence. Five PREDICT sites recommended magnesium for critically asthmatic children, and 55% of respondents used the agent whether recommended by local CPGs or not. Although three of the five sites recommended magnesium regimens with bolus followed by continuous infusion, almost all doctors who used it would only use a single bolus, most often in a dose of 40–50 mg/kg in the mid-range of the available literature43 and similar to the bolus dosage in current Australian6 and British8 guidelines.

This study has some limitations. Principally, it is difficult to determine whether survey responses correlate with actual clinical practice. The findings also reflect physician practice at one point in time, but practice patterns constantly evolve. This survey reports the practice of senior doctors, who may not provide the bulk of care, and at mainly tertiary institutions with dedicated paediatric EDs.

This study has highlighted areas of asthma management where there is wide variation in practice and a limited evidence base. These areas include the role of ipratropium in moderate asthma, optimal dosing of IV salbutamol, and the role of IV salbutamol, IV aminophylline and IV magnesium in severe to critical asthma. The comparative efficacy of IV bronchodilators in particular would benefit from a high-powered, multi-centred trial. At the same time, variation in CPGs and physician practice, in particular regarding salbutamol dosing and use of aminophylline, is the most foreseeable obstacle to multi-centred RCTs.

All PREDICT participating institutions had unique yet largely similar CPGs for acute paediatric asthma management, with recommendations similar to national guidelines.6 7 The creation of guidelines is time consuming, in particular the comprehensive literature reviews and appraisal required.4 Collaborative, evidence-based and regularly updated CPGs based on national guidelines6 7 but focusing on the severe and critical spectrum of childhood asthma would potentially avoid duplication of effort, reduce time and costs of development, and enhance patient outcomes.