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

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Article Reviewed:

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Heliox Therapy in Infants With Acute Bronchiolitis

Martinón-Torres F, Rodríguez-Núñez A, Martinón-Sánchez JM.

Pediatrics 2002; 109:68-73. [abstract; full-text for subscribers/AAP members]

Reviewed by Hiren Trivedi MD , and Katherine Biagas MD, Columbia University, New York, NY

Review posted September 24, 2002

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I. What is being studied?:

The study objective:

To assess the therapeutic effects of Heliox 70:30 in infants with bronchiolitis.

The study design:

Prospective, non-randomized comparison of treatment

The patients included:

Thirty-eight infants, 1 month to 2 years old, admitted to PICU with moderate to severe respiratory distress, attributable to RSV positive bronchiolitis

The patients excluded:

Patients who had underlying cardiopulmonary disease, who suffered from bronchiolitis and /or persistent airway hyperreactivity in the 3 months before the study, or who had received corticosteroids and/or bronchodilators within 2 hours of the initiation of the study were excluded.

The interventions compared:

Conventional treatment (oxygen, fluids, nebulized epinephrine) versus conventional treatment plus Heliox 70:30 administration. However, not all patients in the Heliox group received the same concentration of helium. Heliox 70:30 was administered through a non-rebreather reservoir face mask. Patients who did not maintain oxygen saturations > 90% under this condition had additional oxygen delivered by a nasal cannula placed under the face mask. This diluted the concentration of helium and increased the concentration of oxygen delivered.

The outcomes evaluated:

Primary outcomes were changes in M-WCAS (modified Wood's Clinical Asthma Score) and PICU length of stay. Secondary outcomes were changes in SaO2, heart rate, respiratory rate and end tidal CO2.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

No. The first 19 consecutive patients who fulfilled the inclusion criteria during early winter 1999 were enrolled as a conventional treatment group. The next 19 consecutive patients who fulfilled the inclusion criteria constituted the experimental treatment group.

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

Was followup complete?

Yes, until PICU discharge, however, no criteria for PICU discharge were provided.

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

There was no randomization, however patients were analyzed in the groups they were assigned.

Secondary questions:

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

No. A blinded study is difficult but not impossible to do. Hollman et al (1) used a gas delivery system with three sources of gas flow i.e. oxygen, air and helium. Helium or air administration was accomplished by the respiratory therapist by adjusting a one-way valve located at the junction of the helium and air sources. Blinding was maintained by covering the on-off valves with the tapes, such that the respiratory therapist was the only individual knowledgeable of its position.

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

Yes. Both the groups were similar in baseline characteristics like age, length of the disease course before admission, M-WCAS, heart rate, respiratory rate, SatO2 and EtCO2.

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

Unable to determine as there is no mention about the comparison of conventional treatment like frequency of nebulized epinephrine and FiO2 administered between the two groups. This is particularly important since the study is not blinded, and the use of nebulized epinephrine was given at the discretion of the attending physician. Guidelines for giving epinephrine are not provided. The number of epinephrine treatments received during the study period was not compared between the 2 groups.

III. What were the results?

1. How large was the treatment effect?

M-WCAS, heart rate, respiratory rate and oxygen saturation improved over time in both groups. After 1 hour, M-WCAS was lower in the heliox group compared with the control group. The mean difference in M-WCAS between the groups was 1.9 points. The score continued to decline in both groups although differences in M-WCAS between the heliox and control group remained statistically significant at the end of the observation period. Only data for the first 4 hours was provided in the figures and in the text. The text states that the differences were significant at the end of the "observation period" however the data described in the text is at the 4-hour time point. The difference between the mean scores at the 4 hour time point is: 4.07 Ð 2.39 = 1.68.

The other primary outcome i.e. PICU length of stay was significantly shorter in the heliox group (3.5 ± 1.1 days) compared with the control group (5.4 ± 1.6 days; P < 0.01), the difference between the means being 1.9 days. However, there are no criteria for PICU discharge provided. The secondary outcomes, heart rate and respiratory rate, were also significantly lower in the heliox group compared with the control group during the first 4 hours of treatment. No differences in oxygen saturation and EtCO2 were noted between the two groups.

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

The 95% confidence interval of difference between the two mean for M-WCAS at 1 hour was 1.22 to 2.58. The 95% confidence interval of difference between the two mean for M-WCAS at 4 hour was 1.16 to 2.20. The 95% confidence interval of difference between the two mean for PICU LOS was 1 to 2.8.

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

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

Yes and No. The mean W-CSA score in experimental treatment group and conventional treatment group were 6.7 and 6.6 at baseline indicating patients had moderate to severe respiratory distress. However, most patients with bronchiolitis in our PICU either have underlying cardiopulmonary disease or require mechanical ventilation, or both and none of these patients in this study did. This makes the applicability to my patients questionable.

The improvement in asthma score at the end of 1 hour of treatment was higher in the experimental treatment group than in the conventional treatment group and these differences continued to be significant at the end of the observation period. However the clinical asthma score is a subjective measurement and use of this score in nonrandomized and non-blinded study makes it hard to accept the results as valid. Whether improvement in M-WCAS beyond 4 hours is sustained is not shown. Since criteria for PICU discharge is not provided and the study is not blinded, the validity of this outcome variable is questionable.

2. Were all clinically important outcomes considered?

The modified Wood's clinical asthma score includes subjective measurements. The other primary outcome studied was PICU LOS. The discharge criteria from PICU are not defined and lack of blinding weakens the observation of a difference. The other important outcome to be considered is need for intubation and mechanical ventilation, however no patient required intubation in either group so the impact of the study intervention on this outcome is unknown.

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

The main disadvantage of using heliox is the cost and process of setting up the system for delivery. The most common risks of heliox administration are hypothermia secondary to high thermal conductivity of helium and hypoxemia because of high FiO2 requirement in many infants with bronchiolitis. The small sample size, lack of blinding and randomization makes it difficult to justify its routine use in the treatment of bronchiolitis.

References

1. Hollman G, Shen G, Zeng L, et al. Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis. Crit Care Med. 1998;26(10):1731-6. [abstract]

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