Journal Club 17/09/13 Rob Morton

Heliox Therapy in Bronchiolitis: Phase III Multicentre double blind RCT Chowdhury et al. Pediatrics 2013; 131:661-669

Bronchiolitis season in Sheffield Photo removed for copyright reasons

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 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 air or “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/ £223 Best 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?