Pico journal article presentationMaria Nguyen

BACKGROUND 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 Helium was first isolated from atmospheric air in 1895

Barach first described clinical use of heliox 1935› Heliox is less dense than air › improves flow turbulent laminar flow› decrease work of breathing

Heliox therapy in asthmatics› improved oxygenation› Increase carbon dioxide elimination› Increase expiratory flow› Decrease work of breathing› Enhanced delivery of aerosolized medications to the

peripheral alveoli

Structured Clinical Question

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

Finding the Evidence 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

ObjectiveSingle centered (ED of an urban tertiary care children’s hospital)

Time: between October 2001 to May 2002

Randomized, blind controlled trial

Evaluate the efficacy of heliox versus oxygen in driving continuous albuterol nebulization in children with moderate to severe asthma

Inclusion Criteria Ages 2 to 18 years Pulmonary index (PI) score ≥ 8 Diagnosis of asthma consent

Exclusion Criteria 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

Study

Intervention

Albuterol (continuous) using

PI score was performed at 30 min intervals by a blinded investigator

Study continued until discharge or for 240 minutes

Treatment:

Heliox (70:30)

Control:

Oxygen (100%)

Statistical Analysis 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

Results

ResultsThe mean change in PI score from baseline to 240 minutes

Primary Outcome

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.

Secondary Outcome

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)

0

10

20

30

40

50

60

70

80

ED discharge Discharged < 12 hours after admission

perc

enta

ge (%

)

Heliox Oxygen

CONCLUSION

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

Benefit 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

Drawbacks 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

Objective Single-centered September 1998 to Nov

1998

Primary Outcome› difference in a

modified dyspnea index b/w the 2 groups after 10 and 20 minutes of continuous nebulized albuterol

Secondary› Endotreacheal

intubation in the ED› Admissions to the

hospital

Inclusion Criteria Age 3 to 16 years

previous hx of asthma

a modified dyspnea index of ≥ 4

Exclusion criteria Hx of any other chronic pulmonary disease

Suspected foreign body in the airways

pulmonary edema

Chronic cardiac diseases

CNS disease

Genetic disorder

Immunocompromised states

Method 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)

Modified dyspnea index score was performed at 10 and 20 minutes after treatment

Treatment:

30% O2: 70% helium

Control

30% O2:70% air

Statistical analysis Sample size:

› Detect difference in the modified dyspnea index ≥ 2

› alpha 0.05 › Power: 0.8

N: 17 in each group (total of 34)

Results: Baseline Characteristics

No statistical difference in baseline characteristics b/w the study groups.

Results: Primary Outcome

no significant difference in the median modified dyspnea index scores were noted b/w the study

groups

Results: Secondary Outcomes

0102030405060708090

Intubation Rate of Admission

Perc

ent (

%)

Heliox Oxygen

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)

Conclusion

Albuterol nebulized with heliox offered no clinical benefit over standard therapy in

the initial treatment of moderately severe asthma in the ED

Advantages 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

Drawbacks Low powered study

Short follow-up › Only 20 minutes› After only 1 dose of a continuous albuterol

Adverse effect not addressed

Objective 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

Study Design Prospective

Randomized

Placebo-controlled trial

single centered

May 2006 to December 2007

Inclusion Criteria Age 2 to 21 years

Hx of asthma

Modified Becker Clinical Asthma Score (CAS ≥ 3)

Admission to PICU or asthma ward

Exclusion Criteria 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%

Intervention

Albuterol (continuous or intermittent) using

CAS score was performed at 4 hour intervals by a blinded investigator

Study continued until participants were discharged

Treatment:

Heliox (70:30)

Control:

Air/oxygen (70:30)

Statistical Analysis 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

Results

No significant baseline clinical or demographic differences between the 2 study groups

Primary OutcomeThere were no significant difference in

CAS between the two study groups at any time point after randomization

Primary OutcomeHospital length of stay was not different b/w the 2 groups

Secondary OutcomeThere 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

Secondary Outcomes: PICU subgroups

No differences in time to CAS < 3, PICU length of stay, duration of treatment,

or time of discharge eligibility

Secondary Outcomes: Adverse Events

No difference in the rates of adverse events b/w the 2 groups

Conclusion

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

Advantages Largest pediatric trial involving heliox-

powered albuterol in the treatment

Looks at hospitalization duration

PICU subset

assessment of CAS performed by blind investigator

Drawbacks 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

SUMMARY

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)

FINAL SUMMARY

Based on these data, heliox-powered albuterol cannot be recommended for regular use in the treatment of children with moderate to severe

asthmaticus