Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

Highlighted lines and questions below provide links to the pertinent description of criteria in The EBM User's Guide, now available at the Canadian Centres for Health Evidence

Article Reviewed:

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Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma

Qureshi F, Zaritsky A, Poirier MP.

J Pediatr. 2001;139(1):20-6. [abstract]

Reviewed by Al Torres, MD, MS, University of Illinois College of Medicine at Peoria

Review posted March 9, 2003

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I. What is being studied?:

The study objective:

To determine whether two days of oral dexamethasone (DEX) is more effective than five days of oral prednisone/prednisolone in improving symptoms and preventing relapse in children with acute asthma.

The study design:

A prospective, quasi-randomized, unblinded trial

The patients included:

628 children, aged 2 to 18 years, with a known history of asthma (2 or more episodes of wheezing treated with beta agonists + steroids) who presented to the tertiary care facility's emergency department. Children were enrolled if they required at least 2 doses of nebulized albuterol in the ED.

The patients excluded:

Children were excluded if they reported use of oral steroids with the prior 4 weeks, had a history of intubation, had a varicella exposure within the last 3 weeks, had stridor, had the possible presence of a foreign body, chronic respiratory disease (e.g., cystic fibrosis), cardiac disease, or the need for immediate intervention. Those who vomited 2 doses of the steroids (a second dose was given in case the first dose was vomited within 30 minutes of taking it) were also excluded. Of 1231 eligible patients, 561 patients (46%) were excluded because they met the criteria.

The interventions compared:

On odd enrollment days, the subjects received oral PRED (2 mg/kg. maximum dose 60 mg) and on even enrollment days the subjects received DEX (0.6 mg/kg, maximum single dose 16 mg). Children in the PRED group (n = 261) received liquid prednisolone (Prelone 15 mg/5 mL) or prednisone (USP 10 mg or 20 mg tablets). Children in the DEX group discharged home received a single dose of DEX for the following morning and the children in the PRED group discharged home received a prescription for 4 days of prednisone/prednisolone.

The outcomes evaluated:

The primary outcome measure was the rate of relapse, defined as an unscheduled visit to a medical facility resulting from the patient's or parent's perception of persistent, worsening, or recurrent asthma symptoms in the ten days after discharge from the ED. Secondary outcome measures were the rate of hospitalization (both initially from the ED and after relapse), frequency of vomiting, reported medication compliance, persistence of symptoms, and school or workdays missed.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

No. This is a quasi-randomized study using alternate-day allocation. Patients received oral PRED on odd enrollment days and patients received oral DEX on even enrollment days. This schema was most likely used to improve recruitment and may have led to a more representative sample. Even those patients not enrolled either got DEX or PRED in almost equal distribution.

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

Was followup complete?

Of the 628 patients enrolled, only 533 completed the study. Seventy-two patients were admitted (34 from DEX and 38 from the PRED groups), 12 vomited the medication in the ED (1 DEX vs. 11 PRED, p = 0.008), and two (0.6%) patients in the DEX group and 9 (3%) in the PRED group were lost to follow-up.

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

Yes. The patients lost to follow-up and those enrolled patients excluded for vomiting were included in an intention-to-treat analysis (results discussed below).

Secondary questions:

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

No. The two treatments were given on alternating days and were given in different forms. However, it is unlikely that the treatments being unblinded resulted in a difference in the primary outcome measure, rate of relapse, since it was entirely up to the parent whether they would return with their child to the ED. However, the patients and parents were also not blinded; biases they carried could have potentially affected the outcome.

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

Yes. The two groups were similar in gender, race, vital signs on arrival, previous medications, and initial asthma severity. There was a trend in the DEX subjects towards being younger and weighing less.

5. Aside from the experimental intervention, was the group treated consistently?

Yes. All the children received the first 3 albuterol nebulizations at 20 minute intervals (2.5 mg if weight < 20 kg or 5 mg if weight > 20 kg), and subsequent doses were given as ordered by the physician. Ipratropium bromide was added to 2 or 3 of the initial albuterol nebulizations depending on asthma severity. Oral corticosteroids were given with the second dose of nebulized albuterol. Oxygen was administered to maintained the patient's oxygen saturation ≥ 94%.

III. What were the results?

1. How large was the treatment effect?

The relapse rate was 7.4% (20/272) in the DEX group compared to 6.9% (18/261) in the PRED group (p = 0.84). The intention-to-treat analysis of relapse rates, assuming all those lost to follow-up or who were excluded for vomiting all had relapsed, favored the DEX group, but the difference was not significant [8.7% (24/276) in DEX group vs. 13.5% (38/281) in the PRED group, p = 0.07].

The odds ratio of relapsing if you received DEX instead of PRED was 0.61 (95% CI 0.35 to 1.05). Remember that if a 95% CI of an odds ratio contains one, then the risk or rate of improvement are the same between the two groups and, therefore, not statistically significant.

It is not clear why the authors choose to report the odds ratio; in a prospective controlled trial, the relative risk (RR) is the more appropriate measure. With a relatively low incidence condition (relapse) and large enough population, in this case the OR and RR are quite similar.

There was no significant difference in clinical course in the ED between the two groups (e.g. number of nebulizers administered, time in ED, or asthma severity at discharge).

The one secondary outcome that was significantly different between the two groups was that more parents reported not giving the medication prescribed for home in the PRED group than in the DEX group (4% vs. 0.4%, p = 0.004). However, the children in the PRED group may have not performed significantly different than the DEX group children in this outcome if they were also discharged home with the actual drug instead of a prescription, which required a trip to the drugstore. It is not clear why the investigators risked affecting the trial by only giving the drug to one group, and requiring the other group to obtain the medication on their own.

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

See above.

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

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

Yes, patients with an acute asthma exacerbation presenting to the local ED would likely have a similar outcome if they received DEX vs. PRED. What has not been studied and, therefore, remains unknown is whether the outcome of asthmatic children admitted to the hospital would be similar following PRED vs. DEX.

2. Were all clinically important outcomes considered?

Yes. Cost was not specifically discussed but both medications are rather inexpensive and not likely to differ much.

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

Yes. Patients are more likely to be compliant if they only need to administer one dose of DEX the following day after discharge from the ED which they were given as they were leaving. The risk of adrenal suppression with longer acting corticosteroids such as DEX needs to be appreciated if patients receive prolonged courses or multiple doses within a short period of time.

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