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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Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis

Hollman G, Shen G, Zeng L, et al.

Crit Care Med 1998;26:1731-36. [abstract]

Reviewed by Kate G. Ackerman, M.D., Children's Hospital, Boston

Review posted June 12, 1999

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I. What is being studied?:

The study objective:

To determine the efficacy of a helium-oxygen mixture for improving overall respiratory status in children admitted to the pediatric intensive care unit with acute Respiratory Syncytial Virus (RSV) bronchiolitis.

The study design:

Randomized, double-blind, controlled, crossover study and nonrandomized, prospective study.

The patients included:

18 nonintubated children (ages 3 weeks to 24 months) with signs of acute lower respiratory tract infection and a positive rapid immunoassay for RSV admitted to the pediatric intensive care unit at Wisconsin Children's Hospital. Patients were included if FiO2 was < 0.50.

The patients excluded:

Patients were excluded if they had signs of upper airway obstruction or if they were intubated.

Three "eligible" patients were excluded for technical difficulty setting up the gas delivery system (n=1) or marked agitation (n=2).

The interventions compared:

Treatment with either helium-oxygen or air-oxygen for 20 minute time blocks. The subset of nonrandomized patients received helium-oxygen as initial therapy and were then scored at 20 minutes into therapy.

The outcomes evaluated:

A modified version of Wood et al.'s (1) Clinical Asthma Score was used. The Clinical Asthma Score includes evaluation of cyanosis, inspiratory breath sounds, accessory muscle use, expiratory wheezing, and cerebral function. The investigators modified the score to add further distinctions between degrees of accessory muscle use and expiratory wheezing.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes and No. The mild - moderate group of 13 bronchiolitics were randomized as to the order which they received treatment. The more severe bronchiolitics (n=5) were not randomized; they received treatment immediately. The randomization for the less severe group was done by coin toss.

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

Was followup complete?

Yes. All 18 patients who were entered into the study were included in the data analysis.

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

The randomized patients crossed over. The variable that was being controlled was the timing of the intervention. The randomized less severe patients and the nonrandomized more severe patients were analyzed both together and as separate groups. The analysis of the severe bronchiolitics included one patient from the randomized group with a high clinical asthma score, and this patient was excluded from one analysis of the other randomized patients (correlation of baseline score with change in score).

Secondary questions:

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

Yes and No. For the randomized group, patients and health care staff other than respiratory therapists were blinded to the treatment. The study investigator recording the Clinical Asthma Score, respiratory rate, heart rate, and SpO2 was blinded to the gas mixture. The staff treating and evaluating the nonrandomized patients were not blinded to the treatment.

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

Unclear. All of the patients were had clinical findings of lower respiratory tract disease and RSV positive rapid tests on nasopharyngeal swab samples. However, there were 5 patients with congenital heart disease and two patients with histories significant for upper airway obstruction (surgically corrected laryngomalacia, Treacher Collins syndrome). Although all patients with underlying disease were at home in their usual state of health before developing bronchiolitis, it is unclear whether they were differentially distributed between the two groups.

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

For the most part, it seems that the patients were treated equally. The bronchodilators were not administered during the trial. Most (all but one) patients had been off bronchodilators for one hour prior to the study.

The FiO2 administered during the study was kept constant per study patient, but may have differed between patients.

III. What were the results?

1. How large was the treatment effect?

The treatment effect for the entire study group (18 patients including 5 nonrandomized) was a decrease in the Clinical Asthma Score of 1.23 from baseline (mean 4.25) during helium-oxygen administration (p < .01). The treatment effect for the 13 randomized (less severe disease) patients was a decrease in the Clinical Asthma Score of 0.46 (p < .05). The effect for the more severe group (5 nonrandomized, nonblinded patients and 1 randomized, blinded) was a decrease of 2.67. (The Clinical Asthma Score's maximum value is 10.)

The correlation of baseline Clinical Asthma Score to degree of change in score was reported; the correlation coefficient was 0.72 (p=.009). This was reported for randomized patients only (and excluded the most severely affected patient).

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

The values reported reached statistical significance. The confidence intervals are not reported.

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

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

This study makes it difficult to make an argument to use helium-oxygen mixtures in mild to moderate bronchiolitics (Clinical Asthma Score < 6). The clinical asthma score may not be valid for bronchiolitis as it was developed for asthmatics. The statistically significant change that was noted in the randomized, blinded group was small when one considers the point values assigned in that scale. A change of 0.46 (out of 10 possible points) may mean a change from moderate to mild expiratory wheezing or moderate to mild accessory muscle use. Not only are these changes subjective measurements, the duration of the changes and overall improvement of the patient in the long term is unknown. The study does make an argument for trying oxygen-helium on the more severe bronchiolitics, as they showed possibly clinically significant improvement. However, the small group size (n=6), lack of randomization and blinding may have led to spuriously positive results in this subgroup.

2. Were all clinically important outcomes considered?

This study did not address changes in long term outcome or need for intubation because all patients received the study gas, helium-oxygen. Length of ICU hospitalization and risk for intubation were not considered. A study to answer this question would need to be a prospective, randomized trial containing a moderately large number of patients, as the individual variability of bronchiolitis is great.

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

The main disadvantage to using a helium-oxygen gas mixture is the cost and process of setting up the system for delivery. It is difficult to know whether this cost will be justified in more severe bronchiolitics as the data presented in this study is of insufficient quality in that subgroup. At the current time, it is difficult to justify the cost and labor of helium-oxygen in mild or moderate bronchiolitic patients.

References

1. Wood DW, Downes JJ, Lecks HI. A clinical scoring system for the diagnosis of respiratory failure. Preliminary report on childhood status asthmaticus. Am J Dis Child 1972; 123:227-228. [full PubMed citation]

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