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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Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis.

Osmond MH, Klassen TP.

Acad Emerg Med 1995; 2:651-656 [abstract]

Reviewed by Al Torres, MD, MS

Review posted November 23, 1998

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I. Are the results of the study valid?

A. Primary questions:

1. Did the overview address a focused clinical question?

Yes. The question was "does ipratropium bromide provide an additive, clinically important improvement in children with acute asthma who are being treated with beta-agonists". Main outcome measures varied between studies. Clinical rating score, admission rate, and length of stay in hospital were the major clinical outcomes evaluated. Minor outcome measures included change in forced expiratory volume in 1 second (FEV1) and number of doses of nebulized medicine required.

2. Were the criteria used to select articles for inclusion appropriate?

Yes. Studies included in the meta-analysis met the following selection criteria:

1. Children < 18 years of age who had an acute, unprovoked asthma attack,
2. Treatment with either inhaled ipratropium bromide and a beta-agonist, or treatment with placebo and a beta-agonist,
3. Any measured clinical or physiologic outcome, and
4. Study designed as a randomized, double-blind, placebo-controlled trial.

The authors do not comment much more on study design except to state the dosage of ipratropium employed and the beta-agonist used. For example, no mention is made about single vs. repeated dosing and duration of follow up.

B. Secondary questions:

3. Is it unlikely that important, relevant studies were missed?

Maybe. MEDLINE searches from 1962 to 1992, Science Citation Index from 1986 to 1992, bibliographic reviews of primary research and review articles, and correspondence with authors of recent articles were the approaches included in the meta-analysis. However, there is no mention of the results of the correspondence and no foreign language articles were included in the review.

4. Was the validity of the included studies appraised?

Yes. Methodologic quality of studies was assessed using the following criteria:

1. The study population was considered ideal if it consisted of children with appropriate diagnostic criteria for asthma. The authors, however, failed to define what was meant by "appropriate diagnostic criteria for asthma".
2. ideal baseline comparison of treatment and placebo groups including age, gender, medications, and clinical scores,
3. ideal description of therapeutic regimen if complete and detailed description of the treatment and control interventions was given,
4. ideal outcome measure if it demonstrated validity and reliability,
5. ideal spirometric measurement if patients had previously shown ability to carry out the maneuver, and
6. scientific quality ranked using a Likert scale (1 = extensively flawed to 7 = minimally flawed).

Three of the 6 chosen studies had a low validity score by the authors' asssessment. The maximum score was 7. Two studies scored 3 and one study scored 4.

5. Were assessments of studies reproducible?

Yes. Two reviewers assessed each of the articles included in this meta-analysis. 80 of the 310 initially identified articles were considered possibly relevant by at least one of two reviewers. All 80 of these were reviewed as complete articles by both reviewers. Agreement on which articles to include was 100%. Only six studies were selected for inclusion. In addition, methodologic quality was assessedindependently by the 2 reviewers. A final validity rating was then reached by consensus.

6. Were the results similar from study to study?

Maybe. Outcome measures varied from FEV1 to number of admissions to hospital. Three studies were assessed as having a high methodologic quality (i.e., 6 out of 7 on their Likert scale) and had their data pooled. Statistical homogeneity was good for the three studies of highest quality. Prior to interpreting the results, the reviewers evaluated the studies with a test of homogeneity. A non-significant test of homogeneity suggests that any difference in outcomes between individual studies is likely to be due to chance rather than due to differences in study design. The result of the test of homogeneity for the six studies was p > 0.10. The clinical outcomes, e.g., admission rates, LOS, etc., were similar from study to study.

II. What are the results?

1. What are the overall results of the review?

None of the studies showed a statistically significant difference between treatment and control groups with respect to vital signs, clinical rating score, number of repeat nebulizations, admission rate, length of admission or side effects. The 3 studies with the highest validity all used FEV1 as a main outcome measure. All 3 showed improvement in the percent predicted FEV1 from baseline in the ipratropium group compared to controls. The combined weighted mean difference showed a 12.5% percent improvement in percent predicted FEV1 in the ipratropium group. The overall effect size is 0.88. This is the overall difference between the ipratropium and control groups expressed as the number of standard deviations separating the 2 groups.

2. How precise were the results?

Good. The pooled effect size (95% CI) was 0.88 (0.42 to 1.34) which translates to an improvement in percentage predicted FEV1 of 12.5% (6.6 - 18.4).

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

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

Perhaps. Although none of the studies reviewed included patients admitted to a PICU, there seems little reason to presume the results are not applicable to PICU patients. However, one of the 6 studies suggested that ipratropium bromide may actually cause PEFR to deteriorate in patients with severe airway obstruction.

2. Were all clinically important outcomes considered?

Almost. Although the only significant improvement noted was in FEV1, it may be unreasonable to expect the addition of ipratropium as an adjunctive agent would result in observable improvement in such "important" outcomes as admission rates and length of hospitalization with the small number of patients studied. Admission to the PICU and cost were not addressed.

3. Are the benefits worth the harms and costs? Unclear. The only benefit identified was the reduction in FEV1 at 60 minutes post-treatment. There was no difference in occurrence of side-effects and no information is provided regarding cost.

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Related Reviews:

Qureshi F, Pestian J, Davis P, Zaritsky A. Effect of Nebulized Ipratropium on the Hospitalization Rates of Children with Asthma. New Engl J Med 1998; 339: 1030-35.

• Review, by A. Torres, K. Bysani

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