Journal Club17/09/13

Rob Morton

Heliox Therapy in Bronchiolitis:Phase III Multicentre double blind RCT

Chowdhury et al. Pediatrics 2013; 131:661-669

Bronchiolitis season in Sheffield

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Bronchiolitis season in Sheffield

Photos removed for copyright reasons

Heliox

• Airways in bronchiolitis oedematous and inflamed, lined/blocked with mucus.

• Mix of 21% O2 and 79% Helium- Lighter than air or O2.

• Promotes laminar rather than turbulent flow in congested airways. Also has a higher CO2/02 binary coefficient, may promote alveolar gas exchange.

• Safe, inert

• ? Cheap- $70 dollars a canister- 3-5 canisters a day• = £219 per day

Heliox Cochrane review(2010)Liet et al. Heliox inhalation therapy for bronchiolitis in infants. Cochrane Database Syst Rev.

2010(4):DD006915

• 4 trials including children < 2 years• All on intensive care units• 3 studies showed improvements in symptoms scores at 1 hr

of age• Concluded insufficient evidence, need for a large RCT

BREATHE trial(The Bronchiolitis Randomized Controlled Trial Emergency-Assisted Therapy with Heliox—

An Evaluation )

•4 centres- UK & Australia

• ? 3 Bronchiolitis seasons 2005-2008

Inclusion Criteria

• All infants (<12months) with clinically diagnosed bronchiolitis by a doctor from A&E or wards

• O2 sats <93% in airor

• “Respiratory distress”

• Requiring hospital admission

Randomised to 2 groups

Intervention

• “Heliox” via tight fitting face mask• Nasal cannulae if not tolerated• CPAP if requiring >4L/min O2

flow rate (mask), or >2L/min (NC)

“Controls”

• “Airox”- same delivery criteria

Outcomes

Primary• “Length of time to alleviate hypoxia and respiratory distress”- time

from start of trial gas to clinical stability out of O2 for 1 hour

Secondary• Proportion of each treatment group requiring CPAP• Woods asthma score

CASP(Critical Appraisal Skills Programme)

• 1. Did the trial address a clearly focused issue?

• Yes/No. • Does Heliox improve length of treatment in bronchiolitis?• Is that the relevant issue? Length of stay more important.• ? Severe/ mild bronchiolitics?

• 2. Was the assignment of patients to treatments randomised?

• ?Yes

• Randomised but ?? not all accountable

• ? Not all patients eligible approached for trial?

• 4 centres, 3 seasons = 30 bronchiolitics per year.Adelaide has a population of 1.3million, Sheffield 0.5 million!

• 3. Were all of the patients who entered the trial properly accounted for at the end of the trial?

• ?Yes

But…

Is it worth continuing??

• ………?...........Yes

• 4. Were patients, health workers and study personnel “blind” to the treatment?

• Yes- Good blinding process. Canisters A & B.

• ? Any smell to heliox? Presumably not.

• 5. Were the groups similar at the start of the trial?

Were the groups similar?

• Admitted from A&E? How are they fed? Bottle/ NG/ IV?

• Previous bronchiolitis

• Time from start of symptoms? Time since admission?

• Co-morbidities?

• 6. Apart from the experimental intervention, were the groups treated equally?

• ?- No mention of feeds, other cares. As study well blinded we can presume they were equal across the 2 groups.

• How much O2 was required in each group, how severe were the patients? % O2 has an effect on use of Heliox.

What are the results?

• 7. How large was the treatment effect?

What are the results?

Outcomes

• Length of treatment- Decreased in group who tolerated facemask, particularly those who are RSV+ve.

• If tolerates facemask, and RSV+ve, LOT 1.46 vs 2.01 days, reduces length of treatment by 0.5 days

• ? Decreases need for CPAP (not statistically significant and small numbers)

• “ Reduced respiratory distress”, significant from 8 hrs.?? Take their word for it.

• 8. How precise was the treatment effect?

• No Confidence intervals, IQR instead, as using medians.

What are the results?

9. Can the results be applied to our local population?

• Developed country, same patients and pathology

• Standard care does not usually involve facemasks or CPAP on wards.

• No comparison to standard care.

• ? Can be used for bronchiolitics who are RSV +ve, if they can tolerate a face mask. May prevent need for CPAP & HDU admission?

10. Were all the clinically important outcomes considered?• No.

• Length of treatment of limited use as no comparison to normal care. Need to know length of stay in hospital (impossible to do in this study as no admission/ discharge times)

• Eg., does the intervention/ mask lead to a decrease in feeds and prolong admission?

• How much heliox was used?

11. Are the benefits worth the harms and costs?• How much Heliox was actually used?

5 canisters seems a lot per day/ per patient.= $350 per day/ £223Best intervention group = £312 (1.4 days)

• How much extra cost for the nursing care to fit face mask?

• How much cost for the additional HDU beds?

So….How should a bronchiolitis trial be done?

SABRE: Hypertonic Saline in Acute Bronchiolitis: A Randomised Controlled Trial and Economic Evaluation

BREATHE

• O2 <93% or resp distress • No time limit to recruit• No time of discharge• No economic evaluation

SABRE

• O2 <92% on admission• Strict 90 minute limit to recruit• Criteria for “SABRE” fit for

discharge- includes feeds• Full economic evaluation

Questions?