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Dexamethasone in salbutamol-treated inpatients with acute bronchiolitis: A randomized, controlled trial

Klassen TP, Sutcliffe TS, Watters LK, Wells GA, Allen UD, Li MM

J Pediatr 1997; 130:191-6. [abstract]

Reviewed by Barry Markovitz, MD, Washington University and St. Louis Children's Hospital

Review posted March 3, 1999

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I. What is being studied?:

The study objective:

To determine whether oral dexamethasone, when used with nebulized salbutamol, causes a clinically significant improvement within 24 hours in children less than 15 months of age who are hospitalized with bronchiolitis.

The study design:

A randomized, double blind controlled trial

The patients included:

67 patients with a first time, short-term (less than 7 days) episode of wheezing with evidence of a viral infection (rhinorrhea or temperature >37.5° C), admitted to an inpatient ward with:

1. Age older than 6 weeks, younger than 15 months
2. oxygen saturations <95% on admission
3. Respiratory Distress Assessment Instrument score > 6

The patients excluded:

1. underlying disease affecting cardiopulmonary status, e.g., cystic fibrosis, BPD, congenital heart disease, immunodeficiency
2. asthma diagnosed by a physician
3. wheezing or cough or both that had previously been treated with bronchodilators (not including the current episode)
4. treatment with steroids within 2 weeks
5. any history of adverse reaction to steroids

The interventions compared:

Treated patients received oral dexamethasone (in 70% sucrose), 0.5 mg/kg on admission, then 0.3 mg/kg per day for two additional days or until discharge, whichever came first. Controls received identical appearing placebo (70% sucrose).

The outcomes evaluated:

The RDAI (Respiratory Distress Assessment Instrument) score, a previously validated instrument in patients with bronchiolitis (1). This is a 17 point ordinal scale that assigns points for expiratory (0-4) and inspiratory (0-2) wheezing, location of wheezing (0-2), and supraclavicular, intercostal, and subcostal retractions (0-3 each).

Secondary outcomes included oxygen saturation, respiratory rate, heart rate, duration of hospitalization, use of cointerventions, and readmission rate following initial hospital discharge.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes. Randomization was by computer generation and stratified by age (younger than or older than 6 months).

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes. All 67 of the patients properly randomized were followed to hospital discharge. At follow up 1 week after discharge, only 2 placebo patients could not be reached - they were assumed to have had a good outcome.

Were patients analyzed in the groups to which they were randomized?

Yes; there were no cross-overs. One placebo patient received intravenous hydrocortisone, though it was not noted when in his/her hospital course this occurred.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

Yes. The randomization list was concealed until data analysis was begun. Treated and control patients received identical appearing and tasting solutions.

4. Were the groups similar at the start of the trial?

Yes. Characteristics reported included age, gender, asthma in family, RSV status, oxygen saturation in room air, RDAI scores, and more.

5. Aside from the experimental intervention, were the groups treated equally?

Apparently. All patients (by protocol) received 35% oxygen by tent and salbutamol (0.15 mg/kg) by nebulizer every 4 hours for the first 24 hours. Although 41% of placebo patients received antibiotics and only 29% of treated patients, this difference was not significant. There was no difference in the number of salbutamol treatments, intravenous hydration, or transfer to the intensive care unit (none in either group).

III. What were the results?

1. How large was the treatment effect?

There were no significant differences between groups in the change of the RDAI score, oxygen saturation, or respiratory rate over time. At 24 hours, of 28 placebo patients remaining in hospital, the RDAI decreased by an average of 1.6 points, compared with 1.4 points in the 33 treated patients remaining (p=0.74). The median length of hospital stay in the placebo patients was 48 hrs (95% CI: 42, 54) vs. 57 hrs (95% CI: 38, 76) for the dexamethasone patients (p=0.19).

Four patients in the dexamethasone group were readmitted to the hospital compared to 1 placebo patient (p=0.36).

2. How precise was the estimate of the treatment effect?

There was not a detectable treatment effect. One questions if their sample size was adequate to detect a treatment effect; they include a sample size analysis that suggested the need for 37 patients per group to detect a 2 point difference in the RDAI, with a power of 90%, and an alpha error of 0.05. Although they did not quite achieve 37 patients per group, there is little indication of any tendency of benefit in their results.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

This study does not lend support for the use of dexamethasone for the treatment of bronchiolitis - at least not orally in the doses employed - in this population of infants hospitalized with mild to moderately severe bronchiolitis. This is consistent with other studies that demonstrate no benefit (2-8), but is in contrast to van Woensel et al. (9) that appeared to show a benefit with prednisolone. It is possible that corticosteroids may offer benefit to a different subset of patients, such as those ill enough to be in the intensive care unit. Since none of the patients in this study were in the intensive care unit, the results may not be applicable to our patients.

2. Were all clinically important outcomes considered?

Most clinicians would probably consider duration of hospital stay as the most important outcome measure, rather than a complex scoring system. However, time to actual discharge is often complicated by non-medical factors. The authors cite a previous study (1) where a 2 point difference in the RDAI "clearly differentiated" patients who were admitted compared to those sent home, so this score may represent a reasonable estimate of readiness for discharge.

3. Are the likely treatment benefits worth the potential harms and costs?

This study did not address the risks or costs of dexamethasone therapy.

References

1. Klassen TP, Rowe PC, Sutcliffe T, Ropp LJ, McDowell IW, Li MM. Randomized trial of salbutamol in acute bronchiolitis. J Pediatr 1991; 118:807-11. [abstract]
2. Dabbous IA, Tkachyk JS, Stamm SJ. A double blind study on the effects of corticosteroids in the treatment of bronchiolitis. Pediatrics 1966;37:477-84. [abstract]
3. Leer JA, Green JL, Heimlich EM, Hyde JS, Moffey HL, Young GA, et al. Corticosteroid treatment in bronchiolitis. A controlled collaborative study in 297 infants and children. Am J Dis Child 1969;117:495-503. [abstract]
4. 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;9:181-5. [abstract]
5. Daugbjerg P, Brenoe E, Forchhammer H, et al. A comparison between nebulized terbutaline, nebulized corticosteroid and systemic corticosteroid for acute wheezing in children up to 18 months of age. Acta Paediatr 1993;82:547-551. [abstract]
6. De Boeck K, Van der Aa N, Van Lierde S, Corbeel L, Eeckels R. Respiratory syncytial virus bronchiolitis: A double-blind dexamethasone efficacy study. The Journal of Pediatrics 1997;131:919-921. [abstract]
7. Richter H, Seddon P. Early nebulized budesonide in the treatment of bronchiolitis and the prevention of postbronchiolitic wheezing. The Journal of Pediatrics 1998;132:849-853. [abstract]
8. Roosevelt G, Sheehan K, Grupp-Phelan J, Tanz R, Listernick R. Dexamethasone in bronchiolitis: a randomised controlled trial. The Lancet 1996;348:292-295. [abstract] [PedsCCM EBJC Review]
9. van Woensel JB, Wolfs TF, van Aalderen WM, Brand PL, Kimpen JL. Randomised double blind placebo controlled trial of prednisolone in children admitted to hospital with respiratory syncytial virus bronchiolitis. Thorax 1997; 52: 634-637 [abstract] [PedsCCM EBJC Review]

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