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 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
“Controls”
• “Heliox” via tight fitting face
mask
• Nasal cannulae if not tolerated
• CPAP if requiring >4L/min O2
flow rate (mask), or >2L/min
(NC)
• “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?
Previous bronchiolitis
Time from start of symptoms?
Co-morbidities?
How are they fed? Bottle/ NG/ IV?
Time since admission?
• 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?