Pico journal article presentation Maria Nguyen

1. Pico journal article presentation Maria Nguyen

2. 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

3. 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

4. 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

5. 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

7. Objective • Single 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

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

9. 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

11. Study

12. 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%)

13. 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

14. Results

15. Results The mean change in PI score from baseline to 240 minutes

16. 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.

17. 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)

18. 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

19. 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

20. 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

22. 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

23. Inclusion Criteria • Age 3 to 16 years • previous hx of asthma • a modified dyspnea index of ≥ 4

24. 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

26. 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 Control 30% O2:70% air Treatment: 30% O2: 70% helium

27. 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)

28. Results: Baseline Characteristics No statistical difference in baseline characteristics b/w the study groups.

29. Results: Primary Outcome no significant difference in the median modified dyspnea index scores were noted b/w the study groups

30. Results: Secondary Outcomes 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)

31. Conclusion Albuterol nebulized with heliox offered no clinical benefit over standard therapy in the initial treatment of moderately severe asthma in the ED

32. 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

33. Drawbacks • Low powered study • Short follow-up • Only 20 minutes • After only 1 dose of a continuous albuterol • Adverse effect not addressed

35. 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

36. Study Design • Prospective • Randomized • Placebo-controlled trial • single centered • May 2006 to December 2007

37. Inclusion Criteria • Age 2 to 21 years • Hx of asthma • Modified Becker Clinical Asthma Score (CAS ≥ 3) • Admission to PICU or asthma ward

38. 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%

40. 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)

41. 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

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

43. Primary Outcome There were no significant difference in CAS between the two study groups at any time point after randomization

44. Primary Outcome Hospital length of stay was not different b/w the 2 groups

45. Secondary Outcome 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

46. Secondary Outcomes: PICU subgroups No differences in time to CAS < 3, PICU length of stay, duration of treatment, or time of discharge eligibility

47. Secondary Outcomes: Adverse Events No difference in the rates of adverse events b/w the 2 groups

48. 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

49. Advantages • Largest pediatric trial involving heliox-powered albuterol in the treatment • Looks at hospitalization duration • PICU subset • assessment of CAS performed by blind investigator

50. 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