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September - December 2004: 
Volume 17, Issue 3

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Treatment of children with asthma, bronchiolitis or laryngotracheobronchitis at the emergency room
Abstract
The aim of this study was to investigate treatment regimens of bronchial asthma, bronchiolitis and laryngotracheobronchitis at a pediatric emergency room. This is a retrospective study of children with bronchial asthma, bronchiolitis or laryngotracheobronchitis who presented to the pediatric emergency room of a tertiary care teaching hospital over a 12month period (year 2001). The demographic characteristics, diagnosis and treatment were recorded. During the study period, 881 children with the above mentioned respiratory disorders were examined. It was found that bronchodilators were administered to 89% of them, corticosteroids (inhaled or systemic) to 71%; a combination of bronchodilators and corticosteroids was used in 70% of the patients. The most commonly used bronchodilators were nebulized epinephrine in patients with laryngotracheobronchitis (90%) and salbutamol alone or in combination with ipratropium bromide in those with asthma or bronchiolitis (86% and 70%, respectively). Forty seven per cent of the children received 3 or more medications. We conclude that treatment of asthma and laryngotracheobronchitis with bronchodilators is in accordance with the guidelines of the Hellenic Thoracic Society; inappropriate use of inhaled steroids is though observed. Bronchiolitis is not consistently treated according to current guidelines. Pneumon 2004, 17(3):311-318.
Full text

Introduction

Respiratory infections, i.e. bronchial asthma, acute bronchiolitis and acute laryngitis or laryngotracheobronchitis, are among the most common conditions treated at the emergency room of a hospital.1-7 A significant proportion of children with mild-to-moderate disease are effectively treated at the emergency room with rapid symptom relief, and are then discharged.1 Severe disease may persist despite indicated treatment so that admission to hospital is unavoidable. Evidence regarding the efficacy of various treatment regimens in acute respiratory disorders, especially bronchiolitis, is often controversial.8,9 Furthermore, the introduction of new agents in the management of respiratory diseases sometimes results in practices based on personal evaluation and experience or unconfirmed reports rather than on established evidence.6-9 This may lead to misuse of certain drugs and increased cost of care.

The objective of the present study was to investigate the kind of drugs used and the relative frequency of use of these drugs in the treatment of children with asthma, acute bronchiolitis or acute laryngotracheobronchitis in the emergency room of a university department of pediatrics.

Patients and methods

The medical records of all children with respiratory symptoms who presented to the emergency room of the 4th Department of Pediatrics of the "AHEPA" Hospital of the Aristotle University of Thessaloniki from January 1 through December 31, 2001 were retrospectively reviewed. According to the diagnosis made by duty doctors, children were divided into three diagnostic groups: i) bronchial asthma, ii) acute bronchiolitis, and iii) acute laryngotracheobronchitis. Asthma was diagnosed in children with a history of chronic airway inflammation that manifests itself with exacerbations of asthmatic symptoms that respond to asthma treatment in the absence of other chronic pulmonary disease.10 Bronchiolitis was defined as the first episode of wheezing with tachypnea and hypoxemia in infants aged <2 years with fine crackles and possibly wheezing sounds on auscultation, and radiographic findings of hyperinflation with concurrent upper airway symptoms (nasal congestion, rhinorrhea). The diagnosis of acute laryngotracheobronchitis was based on the presence of "seal-like" barking cough, hoarseness, inspiratory stridor and possibly difficult breathing.10

The age and gender of reviewed children, the administration of bronchodilators and steroids in the emergency room, and the rate of hospitalization according to the condition and provided treatment were recorded.

Statistical analysis: Comparisons between proportions were made using the Fisher's exact test.

Results

In the year 2001, a total of 881 children with bronchial asthma, acute bronchiolitis or laryngotracheobronchitis were treated (Table 1). The treatment regimens applied to the patients who presented to the emergency room are shown in Table 1. Eighty nine per cent of the patients received inhaled nebulized bronchodilators; 71% were offered corticosteroids, either systemic or inhaled. A combination of salbutamol and ipratropium bromide was used in 398 (45%) children. The bronchodilator most commonly used in bronchial asthma and bronchiolitis was salbutamol alone or in combination with ipratropium bromide (in 86% and 70% of patients with asthma or bronchiolitis, respectively); however, inhaled adrenaline was used in 89% of children with laryngotracheobronchitis. Adrenaline was combined with corticosteroids, except in some cases with of laryngotracheobronchitis (n=17) and few patients with bronchial asthma (n=2) or bronchiolitis (n=5) who received adrenaline alone. No child received ipratropium bromide alone. Corticosteroids were frequently used in all three conditions (63%-82%). Systemic corticosteroids were dexamethasone and methylprednisolone; budesonide was the inhaled steroid. Inhaled and systemic corticosteroids were concurrently used in 150 (17%) children. Six hundreds fifteen (70%) children received both bronchodilators and steroids (Table 1).

 

 

Table 1. Age and management of patients at the emergency room.

                                                               Total              Bronchial           Bronchiolitis       Laryngotracheo-

                                                                                      asthma                                            bronchitis

Νο. of patients                                     881                  380  (43%)           221  (25%)          280 (32%)

Age (years, x±SD)                               3.89±3.3          5.36±3.34            0.88±0.55              4.16±2.9

Drug treatment

Epinephrine*                                        290  (33%)        18    (5%)             23  (10%)          249 (89%)

Salbutamol**                                         488  (55%)      327  (86%)           155  (70%)              6   (2%)

Salbutamol + ipratropium bromide        398  (45%)      248  (65%)           145  (66%)              5   (2%)

(± steroids)

Ipratropium bromide + steroids                5    (1%)          4    (1%)               1    (0,45%)         0

Inhaled corticosteroids                         453  (51%)      189  (50%)           118  (53%)          146 (52%)

Oral corticosteroids                                25    (3%)          9    (2%)               9    (4%)              7   (2%)

Combination of oral + inhaled corticosteroids 150         (17%) 43               (11%) 28                (7%) 79   (28%)

Bronchodilators alone (no steroids)     164  (19%)      112  (29%)             25  (11%)            27 (10%)

Steroids alone (no bronchodilators)       13    (1%)          7    (2%)               2    (1%)              4   (1%)

One bronchodilator + corticosteroid     280  (32%)        41  (11%)             20    (9%)          219 (78%)

Two bronchodilators + corticosteroid   335  (38%)      193  (51%)           133  (60%)              9   (3%)

No drug treatment                               90  (10%)        28    (7%)             41  (19%)            21   (7)

* alone or in combination with steroids,  ** alone or in combination with ipratropium bromide or/and steroids

The number of drugs used for the treatment of each of the three conditions is shown in Table 2. Nearly half of the children were given at least three drugs and 7% received more than three drugs. The frequency of using more than two drugs was higher in the bronchiolitis group (61%) (Table 2).

 

Table 2. Number of drugs given to patients presenting to the emergency room.

                                  Total               Bronchial asthma          Bronchiolitis        Laryngotracheobronchitis

Νο. of patients        881                           380 (43%)                 221 (25%)                     280 (32%)

No drug                    90 (10%)                   28   (7%)                   41 (19%)                       21   (7%)

1 drug                      81   (9%)                   41 (11%)                   10   (5%)                       30 (11%)

2 drugs                   297 (34%)                 115 (30%)                   36 (16%)                     146 (52%)

3 drugs                   353 (40%)                 166 (44%)                 106 (48%)                       81 (29%)

>3 drugs                   60   (7%)                   30   (8%)                   28 (13%)                         2   (1%)

Admission to hospital was necessary in 71/881 (9%) children. The proportion of admitted children according to diagnosis is shown in Table 3. The analysis of the treatment given at the emergency room to the children who eventually required hospitalization showed that 42/791 (5%) children who received drug treatment, and 33/90 (37%) who received no drug treatment were admitted (p <0.0001). Hospital admissions by diagnosis and treatment at the emergency room are shown in Table 3. In the bronchial asthma and bronchiolitis groups, the rate of hospitalization was significantly higher among those who were given no drugs at the emergency room compared with those who did receive drugs (p<0.001 and p<0.0001, respectively). In the laryngotracheobronchitis group, too, the rate of hospitalization was higher among those who did not receive drug therapy; however, the difference was not statistically significant due to the low number of admissions (Table 3).

 

 

Table 3. Hospital admissions according to disease and drug treatment at the emergency room.

                                                Total           Bronchial asthma     Bronchiolitis    Laryngotracheobronchitis

No. of patients                      881                       380 (43%)              221 (25%)                280 (32%)

Total admissions (n)               75   (9%)              15   (4%)                54 (24%)                    6   (2%)

Received drug treatment (n) 791 (90%)            352 (93%)              180 (81%)                259 (93%)

Admitted                                 42   (5%)                9   (3%)                28 (16%)                    5   (2%)

Received no drug treatment (n) 90 (22%)             28   (7%)                41 (19%)                  21   (8%)

Admitted                                 33 (37%)                6 (21%)                26 (63%)                    1   (5%)

p*                                          <0.0001                <0.001                 <0.0001                        NS

* for the difference in the rate of hospital admission between patients who received drug treatment and those who did not. NS: not significant.

 

Discussion

The three conditions studied have many common pathogenetic features, which account for the similarity observed in their management. In the present study, we found a similar rate of bronchodilator (80%-91%) and corticosteroid use (63%-82%) in the management of patients in all three groups. Nevertheless, there were differences in the specific agents that were selected for the treatment of each condition. The most commonly used bronchodilator in laryngotracheobronchitis is inhaled adrenaline (89%); in asthma and bronchiolitis salbutamol alone or in combination with ipratropium bromide is the preferred bronchodilator.

Most of the patients with asthma received a combination of the above-mentioned drugs; less than one every five patients received one drug or no drugs at all. Fernantes and Goldie justify the use of combination therapy indicating that, in view of the complexity of the disease, monotherapy cannot provide optimal asthma management.11 Short-acting β2-agonists, e.g. salbutamol, are the well-tried choice in the management of an asthma attack.10 In our study, β2-agonists were given in 86% of children with asthma; in two every three patients β2-agonists were combined with an anticholinergic agent. As demonstrated by Jacoby and Fryer,12 the airways sustain an increased cholinergic load during an asthma attack; hence, the use of anticholinergic agents, i.e. ipratropium bromide, is very effective in the management of asthma attacks. Nevertheless, monotherapy with anticholinergic agents either in the management of asthma attacks or in the long-term treatment for the prevention of asthma symptoms is not warranted.11 Their addition to the combination of salbutamol with corticosteroids significantly reduces the rate of hospitalization.13 The administration of inhaled epinephrine in a percentage, although small, of children with bronchial asthma may be due to the difficulty in differentiating between bronchiolitis and bronchial asthma. There is no consensus in the definitions of the two conditions, in particular bronchiolitis; in addition, the first attack of bronchial asthma may be mistaken for bronchiolitis.10

Following the establishment of the role of airway inflammation in conjunction with bronchospasm in the pathogenesis of bronchial asthma, the use of corticosteroids rose sharply.14 Taking into account available evidence, the Hellenic Thoracic Society recommends the use of oral corticosteroids in children presenting with an asthma attack; the dose of oral corticosteroids is adjusted according to the severity of the asthma attack and the previous use of corticosteroids. The efficacy of inhaled steroids in the management of asthma attacks is questionable.10 In our study, corticosteroids were given in two every three children, more often than not in combination with bronchodilators. However, inhaled corticosteroids (budesonide 0.25 mg/mL) were the preferred choice despite current recommendations. Moreover, in severe cases, comprising about 19% of the study population, systemic corticosteroids, e.g. methylprednisolone, were concurrently given.

Acute bronchiolitis is a viral infection most commonly caused by the respiratory syncytial virus (RSV) and characterized by inflammatory changes probably with concurrent smooth muscle contraction.16 Therefore, it would be expected that the use of bronchodilators and anti-inflammatory drugs in the management of bronchiolitis be justified. Several studies have shown that β2-agonists provide only a slight improvement of the clinical status and oxygenation of infants with bronchiolitis.17,18 Still, other studies failed to demonstrated clinical improvement nor reduced rate of hospital admissions with the use of β2-agonists.19 Despite controversy about their efficacy, in our study bronchodilators, primarily β2-agonists such as salbutamol, were given in 80% of the infants presenting to the emergency room with bronchiolitis. With regard to the use of anticholinergic agents in the management of acute bronchiolitis, ipratropium bromide was added to salbutamol in a significant proportion of infants with bronchiolitis, although the available evidence does not suggest any additional benefit from this combination.20 Epinephrine was administered in less than 10% of infants with bronchiolitis; however, many studies have shown that the use of inhaled epinephrine is safe and effective, in that it causes marked clinical improvement, and faster than β2-agonists too.21,22 The low rate of epinephrine use suggests that most of the cases included in our study had mild-to-moderate bronchiolitis. Much of the controversy regarding the use of bronchodilators in infants with bronchiolitis has been attributed to the varying severity of the cases included in different studies.16 A systematic meta-analysis aiming to answer relevant questions concluded that the use of bronchodilators in mild-to-moderate bronchiolitis leads to a slight short-term improvement.23,24 This conclusion is in accordance with the general experience of pediatricians that bronchodilators do indeed improve symptoms in most infants. Therefore, bronchodilators are currently given to most infants with bronchiolitis, as demonstrated in the present study as well; however, their use should be limited to a single agent at a time. According to the Greek Consensus, a trial dose of a β2-agonist may be used and, if there is response, the dose may be repeated accordingly.10

Corticosteroids may theoretically be helpful in the management of bronchiolitis, since airway inflammation is the primary pathologic lesion. However, their efficacy in the management of this condition has not been established.20,25-29 Previous studies had failed to demonstrate a favorable effect of oral steroids.25-28 Still, a recent randomized double blind study that included 70 infants presenting to the emergency room with bronchiolitis showed a significantly lower rate of hospitalization among infants treated with oral dexamethasone compared to those who received placebo.20 Furthermore, the same study showed a significant clinical improvement within 4 hours, but not at day 7 after drug treatment. Similarly, a recent meta-analysis indicated a significantly more marked improvement in hospitalized infants who received steroids compared with those who did not.29 Evidence regarding the use of inhaled steroids in the acute management of bronchiolitis is scant and does not suggest a short- or long-term favorable effect.20 The Greek Consensus on the management of bronchiolitis discourages the use of corticosteroids on previously healthy infants with acute bronchiolitis.10 In our study, the use of corticosteroids, mainly inhaled (66%), but both inhaled and systemic in 13%, for the acute phase treatment in two thirds of infants with bronchiolitis, was discordant with published evidence or the Greek Consensus recommendations. Overuse of corticosteroids may partly be attributed to the lack of a universally accepted definition of bronchiolitis that makes it difficult for duty doctors to eliminate the possibility of bronchial asthma in infants with recurrent bronchiolitis. At the same time, however, the need for continuing education and update of pediatricians is stressed. A significant progress toward this direction is the publication of the Greek Consensus for the management of the three respiratory diseases dealt with in the present study; this publication was made by the Hellenic Thoracic Society two years after the completion of our study.

Laryngotracheobronchitis was the second most common respiratory disease among children presenting to the emergency room. In the past, the management of this condition was based on breathing water vapor-rich air, but the efficacy of such a treatment has not been verified.16,31 Epinephrine is the drug of choice; its effect lasts for about 2 hours, after which the symptoms of the disease may recur.10,32,33 Eighty nine per cent of the children who presented to the emergency room with laryngotracheobronchitis received inhaled adrenaline; steroids were added to adrenaline in 81% of the children. There is ample evidence that children presenting to the emergency room with laryngotracheobronchitis should receive corticosteroids as soon as possible. The use of corticosteroids has been shown to conduce to better outcomes and lower rates of hospitalization.33-36 Dexamethasone is considered the agent of choice. Dexamethasone was given to less than 1 every three children with laryngitis, whereas inhaled corticosteroids were inappropriately given to almost 4/5 of the children. Certainly, inhaled corticosteroids too are effective in the management of acute laryngotracheobronchitis37-39 and their addition to dexamethasone enhances response to dexamethasone.35 Hence, Hellenic Thoracic Society recommends the use of oral dexamethasone in acute laryngotracheobronchitis; in moderate-to-severe disease oral dexamethasone should be combined with inhaled corticosteroids.10

In our study, the rate of hospitalization among children who received no drugs at the emergency room was significantly higher compared to children who were treated with drugs. The difference was significant (p<0.0001) in infants and children who presented with asthma or bronchiolitis. These results, although suggestive of the effectiveness of treatment at the emergency room with regard to the reduction of the rate of hospital admissions, should be evaluated with caution, since the study was not designed so as to show such an effect. It is hence likely that infants with severe disease were admitted before any treatment was initiated at the emergency room. Individual studies, as well as meta-analyses indicate that bronchodilators have no effect on the rate of hospital admissions among children with bronchiolitis;19,23 however, there are reports of reduced rate of hospital admissions among infants and children with bronchial asthma or bronchiolitis who received combination therapy with β2-agonists and corticosteroids.13,20

Conclusively, the use of bronchodilators in children presenting at the emergency room with asthma or laryngotracheobronchitis is in accordance with the guidelines of the Hellenic Thoracic Society, but corticosteroids are inappropriately used. As regards the management of bronchiolitis, there is no consensus for the appropriate treatment; nevertheless, the current guidelines are not consistently adhered to. Inhaled corticosteroids are often overused in all three patient groups; this may be due to the impression that inhaled drugs have a faster onset of action. Continuing education and update of pediatricians on new scientific evidence and the establishment of evidence-based treatment protocols in accordance with the Hellenic Thoracic Society guidelines will concur to a more rational use of drugs in the management of these respiratory diseases in the acute care setting. This will not only lead to more rapid symptom relief and lower rates of hospitalization, but will further limit overuse of certain drugs and thus incurred cost of care. Certainly, we are aware that our results have a limited potential of extrapolation since they come from the emergency room of a single hospital in the Prefecture of Thessaloniki and reflect the care provided during a certain year. Nevertheless, if similar studies were to be conducted in the emergency rooms of all hospitals in Northern Greece, it is quite likely that similar results would be obtained, since the center that conducted the present study is the cradle of training in pediatrics in Northern Greece.

 

 

REFERENCES

1. Asher MI. Infections of the upper Respiratory tract. In: Taussig LM, Laudau LI, Eds, Pediatric Respiratory Medicine. St Louis, The CV Mosby Co 1999; 530-547.

2. Von Mutius E, Morgan WJ. Acute, chronic and wheezy brochiolitis. In: Taussig LM, Laudau LI, Eds, Pediatric Respiratory Medicine. St Louis, The CV Mosby Co 1999; 547-56.

3. Denny FW. Acute lower respiratory tract infections. General considerations. In: Taussig LM, Laudau LI, Eds, Pediatric Respiratory Medicine. St Louis, The CV Mosby Co 1999; 556-572.

4. Everard ML. Acute brochiolitis and pneumonia in infancy resulting from the respiratory syncytial virus. In: Taussig LM, Laudau LI, Eds, Pediatric Respiratory Medicine. St Louis, The CV Mosby Co 1999; 580-595.

5. Miller MA, Beu-Ami T, Daum RS. Bacterial pneumonia in neonates and older children. In: Taussig LM, Laudau LI, Eds, Pediatric Respiratory Medicine. St Louis, The CV Mosby Co 1999; 595-664.

6. Herendeen NE, Szilagy PG. Infection of the upper respiratory tract. In: Behrman RE, Kliegman RM, Jenson HB. Eds, Nelson Textbook of Pediatrics. Philadelphia, W.B. Saunders Co 2000; 1261-1266.

7. Orenstein DM. Acute inflammatory upper airway obstruction. In: Behrman RE, Kliegman RM, Jenson HB. Eds, Nelson Textbook of Pediatrics. Philadelphia, W.B. Saunders Co 2000; 1274-1279.

8. Turner TWS, Evered LM. Are bronchodilators effective in bronchiolitis? Ann Emerg Med 2003, 42:709-711.

9. Nelson R. Bronchiolitis drugs lack convincing evidence of efficacy. Lancet 2003; 361:939.

10. Ελληνική Πνευμονολογική Εταιρεία. Ελληνικές Ομοφωνίες για τη διάγνωση και αντιμετώπιση ασθματικού παροξυσμού, οξείας βρογχιολίτιδας, οξείας λαρυγγοτραχειοβρογχίτιδας. Αθήνα 2003.

11. Fernandes LB, Goldie RG. The single mediator approach to asthma therapy: is it so unreasonable? Curr Opin Pharmacol 2003; 3:251-256.

12. Jacoby DB, Fryer AD. Anticholinergic therapy for airway diseases. Life Sciences 2001; 68:2565-2572.

13. Qureshi F, Pestian J, Davis P, Zaritsky A. Effect of nebulized ipratropium on the hospitalization rates of children with asthma. N Engl J Med 1998; 339:1030-1035.

14. de Blic J, Scheinmann P. Early use of inhaled corticosteroids in infancy. Pediatr Respir Rev 2000, 1: 368-371.

15. Tinkelman D. Beta agonists: present use and controversies. Respir Immunol 1998; 149:197-200.

16. Wright RB, Pomerantz WJ, Luria JW. New approaches to respiratory infections in children. Bronchiolitis and Croup. Emerg Med Clin N Am 2002; 20:93-114.

17. Klassen TP, Rowe PC, Sutcliffe T, Ropp Lj, McDowell Iw, Li MM. Randomized trial of salbutamol in acute bronchiolitis. J Pediatr 1991; 118:807-811.

18. Schuh S, Canny G, Reisman JJ, Kerem G, Bentur L, Petric M, Levison H. Nebulized albuterol in acute bronchiolitis. J Pediatr 1990; 117:633-637.

19. Patel H, Gouin S, Platt RW. Randomized, double-blind, placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis. J Pediatr 2003; 142: 509-514.

20. Schuh S, Coates AL, Binnie R, Allin T, Goia C, Corey M, Dick PT. Efficacy of oral dexamethasone in outpatients with acute bronchiolitis. J Pediatr 2002; 140: 27-32.

21. Sanchez I, De Koster J, Powell RE, Wolstein R, Chemick V. Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis. J Pediatr 1993; 122: 145-151.

22. Reijonen TM, Korppi Μ, Pitkakangas S, Tenhola S, Renes K. The clinical efficacy of nebulized racemic epinephrine and albuterol in acute bronchiolitis. Arch Pediatr Adolesc Med 1995; 149:686-692.

23. Kellner J, Ohlsson A, Gadomski AM, Wang EEL. Efficacy of bronchodilator therapy in bronchiolitis: a meta-analysis. Arch Pediatr Adolesc Med 1996; 150:1166-1172.

24. Kellner JD, Ohlsson A, Gadomski AM, Wand EEL. Bronchodilator therapy in bronchiolitis. In: The Cochrane Library, issue 4. Oxford: Update Software, 1998.

25. Springer C, Bar-Yishay E, Uwayyed K, Avital A, Vilozni D, Godfrey S. Corticosteroids do not affect the clinical or physiological status of infants with bronchiolitis. Pediatr Pulmonol 1990; 9:181-185.

26. Berger I, Argaman Z, Schwartz SB, Sagal E, Kiderman A, Branski D, Kerem E. Efficacy of corticosteroids in acute bronchiolitis: short-term and long-term follow-up. Pediatr Pulmonol 1998; 26:162-166.

27. Law BJ, DeCharvalho V. Pediatric investigators collaborative network on infections in Canada. Respiratory syncytial virus infection in hospitalized Canadian children: regional differences in patient populations and management practices. Pediatr Infect Dis J 1993; 12:659-663.

28. Roosevelt G, Sheehan K, Grupp-Phelan J, Tanz RR, ListernickR. Dexamethasone in bronchiolitis: a randomized clinical trial. Lancet 1996; 348:292-295.

29. Garrison MM, Christakis DA, Harvey E, Cummins P, Davis RL. Systemic corticosteroid in infant bronchiolitis: a metaanalysis. Pediatrics 2000; 105:E44

30. Cade A, Brownlee KG, Konway SP, Haigh D, Short A, Brown J, Dassu D, Mason SA, Philips A, Eglin R, Graham M, Chetcuti A, Chatrath M, Hudson N, Thomas A, Chetcuti PA. Randomized placebo controlled trial of nebulized corticosteroids in acute respiratory syncytial virus bronchiolitis. Arch Dis Child 2000; 82:126-130

31. Lebecque P. Childhood croup. Arch Pediatr 1999; 6:768-774.

32. Kristjansson S, Berg-Kelly K, Winso E. Inhalation of racemic adrenaline in the treatment of mild and moderately severe croup: Clinical symptom score and oxygen saturation measurements for the evaluation of treatment effects. Acta Paediatr 1994; 83:1156-60.

33. Ledwith CA, Shea LM, Mauro RD. Safety and efficacy of nebulized racemic epinephrine in conjunction with oral dexamethasone and mist in the outpatient treatment of croup. Ann Emerg Med 1995; 25:331-37.

34. Johnson DW, Jacobson S, Edney PC, Hadfield P, Mundy ME, Schuh S. A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. N Engl J Med 1998; 339:498-503.

35. Klassen TP, Watters LK, Feldman ME, Sutcliffe T, Rowe PC. The efficacy of nebulized budesonide in dexamethasone treated outpatients with croup. Pediatrics 1996; 97: 463-466.

36. Geelhoed GC, Macdonald WBG. Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg. Pediatr Pulmonol 1995; 20:362-368.

37. Fitzgerald D, Mellis C, Johnson M, Allen H, Cooper P, Van Asperen P. Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup. Pediatrics 1996; 5:722-725.

38. Godden CW, Campbell MJ, Hussey M, Cogswell JJ. Double blind placebo controlled trial of nebulised budesonide for croup. Arch Dis Child 1997; 76:155-158.

39. Husby S, Agertoft L, Mortensen S, Pedersen S. Treatment of croup with nebulized steroid (budesonide): A double-blind, placebo-controlled study. Arch Dis Child 1993; 68:352-355.

References