
Asthma is a common, potentially life-threatening
condition

Accounts for 2 million pediatric ED visits annually

500, 000 hospitalizations

~ $ 6 billion in total healthcare expenditures on an
annual basis

high morbidity and mortality associated with status
asthmatics

Helium was first isolated from atmospheric air in 1895

Barach first described clinical use of heliox 1935

Heliox therapy in asthmatics
› Heliox is less dense than air
› improves flow turbulent  laminar flow
› decrease work of breathing
›
›
›
›
›
improved oxygenation
Increase carbon dioxide elimination
Increase expiratory flow
Decrease work of breathing
Enhanced delivery of aerosolized medications to the
peripheral alveoli

Patient: Pediatric Patients with moderate to
severe asthma requiring albuterol

Intervention: albuterol nebulized in heliox

Comparison: Albuterol in oxygen/air

Outcome:
› Clinical improvement
› Admission rate
› Duration of hospitalization

Search: Pubmed

Key words: Asthma, heliox nebulized albuterol/b-2 agonist

Limit the search to:
›
›
›
›
a. Birth to 18 years
b. English language
c. Randomized Clinical Trial
d. Humans

Results: 43

3 studies:
›
Helium/oxygen-driven albuterol nebulization in the treatment of children with moderate to severe
asthma exacerbations: A randomized, Controlled Trial
›
Albuterol nebulized in heliox in the initial ED treatment in pediatric asthma: a blinded, randomized
controlled trial
›
Helium/oxygen-driven albuterol nebulization in the management of children with status
asthmaticus: A randomized, placebo-controlled trial
Single
centered (ED of an urban tertiary care
children’s hospital)
Time:
between October 2001 to May 2002
Randomized,
Evaluate
blind controlled trial
the efficacy of heliox versus oxygen
in driving continuous albuterol nebulization in
children with moderate to severe asthma
Ages 2 to 18 years
 Pulmonary index (PI) score ≥ 8
 Diagnosis of asthma
 consent


Presence of cyanotic heart disease

concurrent bronchiolitis (+ RSV)

lobar pneumonia on CXR

Croup

foreign-body aspiration

Pre-existing chronic lung disease

Underlying chronic medical conditions

Pregnancy/nursing

Intolerance of nonrebreather face mask

Use of oral or parenteral corticosteroids within the preceding 72 hours
Albuterol (continuous) using
Treatment:
Control:
Heliox (70:30)
Oxygen (100%)

PI score was performed at 30 min intervals by a
blinded investigator

Study continued until discharge or for 240 minutes

Clinical improvement in PI defined as an
decrease of ≥ 2 units over study time

Sample size calculated
› 2 units were considered to the minimum
relevant difference
› alpha: 0.05
› power 80%

N: 30 with 15 in each group
The mean change in PI score from baseline to 240 minutes
At 125 minutes, the heliox group showed a clinically significant
absolute mean PI improvement compared with the oxygen
group (p< 0.05).
A clinically significant difference of absolute mean PI scores (p
< 0.01) was sustained at 150, 180 and 240 minutes.
Heliox
Oxygen
80
percentage (%)
70
60
50
40
30
20
10
0
ED discharge
Discharged < 12 hours after admission

67% patients in heliox group were discharged from the ED compared
with 33% in the oxygen group (P = 0.07)—not statistically significant

73% patients in the heliox group were discharged home from hospital
in < 12 hours compared with 33% in the conventional group (P < 0.05)
Continuously nebulized albuterol delivered
by heliox was associated with a greater
degree of clinical improvement
compared with that delivered by
oxygen among children with moderate
to severe asthma

Randomized

Blinded

Follow up was completed:
› Telephone f/u at 24-hour and 7 day (none
returned to ED or had unscheduled visit to
PMD

Lack of blinding by the patient may have affected the PI score
›
›
patient’s sense of dyspnea can be affected by knowing
this knowledge can in turn influence respiratory rate and retractions 
affect PI score

Lack of blinding for the attending physician who determined
admission, ED discharge and hospital discharge

Albuterol 15 mg/hour of continuous albuterol to all patients (weight
based: 0.45 mg/kg/hour )
›
4 in heliox and 5 in oxygen group received > than the dose recommended

Not adequately powered for secondary outcomes

Adverse effects not measured

Use of face mask for delivering aerosolized medications may limit
applicability to younger-aged children who may not tolerate face
masks

Single-centered

September 1998 to Nov
1998

Primary Outcome

Secondary
›
difference in a
modified dyspnea
index b/w the 2 groups
after 10 and 20 minutes
of continuous
nebulized albuterol
Endotreacheal
intubation in the ED
› Admissions to the
hospital
›

Age 3 to 16 years

previous hx of asthma

a modified dyspnea index of ≥ 4

Hx of any other chronic pulmonary disease

Suspected foreign body in the airways

pulmonary edema

Chronic cardiac diseases

CNS disease

Genetic disorder

Immunocompromised states

all patients received:
3 doses of aerosolized albuterol
› IVF at maintenance
› 2mg/kg IV methylprednisolone
›


continuous albuterol therapy (0.45 mg/kg, maximum dose 15 mg/hr)
Treatment:
Control
30% O2: 70% helium
30% O2:70% air
Modified dyspnea index score was performed at 10 and 20 minutes
after treatment

Sample size:
› Detect difference in the modified dyspnea
index ≥ 2
› alpha 0.05
› Power: 0.8

N: 17 in each group (total of 34)
No statistical difference in baseline
characteristics b/w the study groups.
no significant difference in the median
modified dyspnea index scores were noted
b/w the study groups
Heliox
Oxygen
90
80
Percent (%)
70
60
50
40
30
20
10
0
Intubation
Rate of Admission
None of the study subjects were intubated during their ED stay
Rate of admission was 60% in heliox group and 81% in the oxygen group (p = 0.181)
Albuterol nebulized with heliox offered no
clinical benefit over standard therapy in
the initial treatment of moderately
severe asthma in the ED

Randomized

Blinding was maintained
› children did not speak with the study
investigator assigning the modified dyspnea
index scores
› tanks remained covered during assessment

Adequately powered to detect changes
for primary outcome

Low powered study

Short follow-up
› Only 20 minutes
› After only 1 dose of a continuous albuterol

Adverse effect not addressed

Primary outcome:
› Effect of heliox-powered albuterol therapy
on hospital length of stay and clinical status
in children with moderate to severe status
asthmatics

Secondary outcome
› Length of time required to reach a CAS ≤ 3
› Adverse event rate
› PICU length of stay

Prospective

Randomized

Placebo-controlled trial

single centered

May 2006 to December 2007

Age 2 to 21 years

Hx of asthma

Modified Becker Clinical Asthma Score
(CAS ≥ 3)

Admission to PICU or asthma ward

need for invasive or non-invasive
mechanical ventilation

Impending respiratory failure (PaCO2 >
60, AMS)

Need for supplemental oxygen with an
FiO2 ≥ 0.4 to maintain oxygen saturations
> 90%
Albuterol (continuous or intermittent) using
Treatment:
Control:
Heliox (70:30)
Air/oxygen (70:30)

CAS score was performed at 4 hour intervals by a
blinded investigator

Study continued until participants were discharged

Sample size: N 348 (174 participants in
each group)
› 0.5 day reduction in hospital length of stay
› power of 80%
› Alpha 0.05

P value ≤ 0.05 is considered significant
No significant baseline clinical or demographic differences between the 2 study
groups
There were no significant difference in CAS
between the two study groups at any
time point after randomization
Hospital length of stay was not different b/w the 2 groups
There were no difference between groups in the time to CAS < 3
No difference b/w the groups in CAS score at 24-hour and at the end of
the study
No differences in time to CAS < 3, PICU
length of stay, duration of treatment, or
time of discharge eligibility
No difference in the rates of adverse events b/w the 2
groups
Heliox-powered nebulized albuterol
therapy does not reduce the duration of
hospitalization nor hasten the time to
clinical improvement for children
admitted to the hospital with moderate
to severe status asthmaticus

Largest pediatric trial involving helioxpowered albuterol in the treatment

Looks at hospitalization duration

PICU subset

assessment of CAS performed by blind
investigator

Excluded patients with CAS < 3 inpatient
(may have been CAS ≥ in ED)

Underpowered (low enrolment)

Healthcare team involved in therapeutic
decision-making as well as transfer and
discharge assessments were not blinded

albuterol nebulized with heliox offered no clinical benefit
over standard therapy in the initial treatment of moderately
severe asthma in the ED (2nd study)

Continuously nebulized albuterol delivered by heliox was
associated with a greater degree of clinical improvement
compared with that delivered by oxygen among children
after the initial ~ 2 hours (1st study)

Heliox-powered nebulized albuterol therapy does not
reduce the duration of hospitalization nor hasten the time to
clinical improvement for children admitted to the hospital
with moderate to severe status asthmaticus (3rd study)
Based on these data, heliox-powered albuterol
cannot be recommended for regular use in the
treatment of children with moderate to severe
asthmaticus