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Heliox for croup in children

  1. Irene Moraa1,*,
  2. Nancy Sturman2,
  3. Treasure McGuire3,
  4. Mieke L van Driel2,4,5

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 7 DEC 2013

Assessed as up-to-date: 12 NOV 2013

DOI: 10.1002/14651858.CD006822.pub4


How to Cite

Moraa I, Sturman N, McGuire T, van Driel ML. Heliox for croup in children. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD006822. DOI: 10.1002/14651858.CD006822.pub4.

Author Information

  1. 1

    Pharmacy Australia Centre of Excellence, School of Pharmacy, Woolloongabba, Australia

  2. 2

    The University of Queensland, Discipline of General Practice, School of Medicine, Brisbane, Queensland, Australia

  3. 3

    Bond University, Faculty of Health Sciences and Medicine, Gold Coast, Queensland, Australia

  4. 4

    Bond University, Centre for Research in Evidence-Based Practice, Gold Coast, QLD, Australia

  5. 5

    Ghent University, Department of General Practice and Primary Health Care, Ghent, Belgium

*Irene Moraa, School of Pharmacy, Pharmacy Australia Centre of Excellence, 20 Cornwall Street, Woolloongabba, Australia. imoraa@yahoo.com.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 7 DEC 2013

SEARCH

 
Characteristics of included studies [ordered by year of study]
Terregino 1998

MethodsRandomised controlled trial


Participants15 participants (8 intervention, 7 controls) who presented to the ED with features of croup, aged 6 months to 4 years. Excluded if severe respiratory distress, oxygen saturation < 95% on 2 L/min oxygen, or other causes of upper airway obstruction


InterventionsIntervention group: humidified helium-oxygen mixture (70%/30%) for 20 minutes

Control group: humidified oxygen (30%) for 20 minutes


OutcomesPrimary: change in croup score at 20 minutes

Secondary: change in heart rate, respiratory rate, oxygen saturation


NotesNo information on funding source or potential conflict of interest of the authors has been provided


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskUse of sequentially, sealed envelopes available only to the respiratory therapist

Allocation concealment (selection bias)Low riskAllocation was adequately concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants and outcome assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo evidence of missing outcome data

Selective reporting (reporting bias)Low riskAll expected study outcomes were reported

Other biasUnclear riskConvenience sample used

Weber 2001

MethodsRandomised controlled trial


Participants29 participants (14 intervention, 15 controls) who presented to the ED with features of moderate to severe croup (corresponding to a modified Taussig croup score ≥ 5), aged 6 months to 3 years. Excluded if known congenital cardiac or tracheo-broncho-pulmonary disease or if other causes of stridor


InterventionsAll patients received intramuscular dexamethasone 0.6 mg/kg

Intervention group: helium-oxygen inhalation (70%/30%) and up to 2 doses of nebulised normal saline over 3 hours

Control group: oxygen (100%) and up to 2 doses of nebulised racaemic epinephrine over 3 hours


OutcomesPrimary: change in croup score at 30, 60, 90,120, 150, 180, 240 minutes

Secondary: change in heart rate, respiratory rate, oxygen saturation


Notes"This study was funded, in part, by the Hurley Respiratory Therapy Department, Hurley Medical Center."

No information on authors' conflict of interest provided


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskUse of computer-generated randomisation scheme

Allocation concealment (selection bias)Low riskAllocation was adequately concealed

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants and outcome assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskLack of ITT analysis

Selective reporting (reporting bias)High riskLack of reporting of some of the expected outcome data

Other biasUnclear riskGiven the described patient selection process there may be a further potential risk of bias

Pardillo 2009

MethodsProspective, randomised, open clinical trial


Participants47 participants (23 control, 24 intervention) with moderate croup (Taussig score between 5 to 8) aged 6 to 36 months. Excluded - patients with congenital or acquired cardiac conditions, bronchopulmonary dysplasia or stenosis or malformations of the trachea, bronchospasm at diagnosis, intolerance of oral dexamethasone or children treated with corticosteroids in the previous 2 weeks


InterventionsAll patients received oral dexamethasone 0.3 mg/kg to max of 10 mg. Rescue treatment was nebulised epinephrine and oxygen via nasal route if saturation fell below 92%

Control group - no treatment

Intervention group - heliox 70%/30% via a mask with a reservoir to prevent re-inhalation flow rate of 10 L/min for 1 hour


OutcomesPrimary outcomes: change in croup score and respiratory rate at 60 and 120 minutes

Secondary outcomes: need for nebulised rescue epinephrine, admission rate, re-consultation within the following 72 hours


NotesNo information on funding source or potential conflict of interest of the authors has been provided


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskUse of a computer-generated randomisation scheme

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
High riskOpen-label study; assessors knew which arms of the study participants belonged to

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere were no participants lost to follow-up

Selective reporting (reporting bias)High riskResults for the patients who required rescue epinephrine reported, but outcomes for those who were admitted or who re-presented at 72 hours were not reported

Other biasUnclear riskAssessors may have influenced overall outcomes due to the lack of blinding

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Beckmann 2000Case report (2009 and 2013 searches)

Brown 2002Review (from 2013 search)

Choi 2012Review (from 2013 search)

DiCecco 2004Case report

Duncan 1979Case series (2009 and 2013 searches)

Frazier 2010Review (from 2013 search)

Gupta 2005Review

Iglesias 2007Cohort study

Johnson 2009Review

Kaditis 1998Not RCT (from 2013 search)

Kline-Krammes 2012Review (from 2013 search)

Myers 2004Review

Myers 2006Review (2009 and 2013 searches)

Nelson 1982Case series

Nicolai 2012Review (from 2013 search)

Pitluk 2011Not RCT (from 2013 search)

Rosekrans 1998Not RCT (from 2013 search)

Smith 1999Case reports

Wald 2010Not RCT (from 2013 search)

Wright 2005Not RCT (from 2013 search)

 
Comparison 1. Heliox versus oxygen 30%

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mean change in croup score115Mean Difference (IV, Fixed, 95% CI)0.83 [-0.70, 2.36]

 2 Westley croup score at 20 min115Mean Difference (IV, Fixed, 95% CI)-0.57 [-1.46, 0.32]

 3 Heart rate at 20 min115Mean Difference (IV, Fixed, 95% CI)14.5 [-8.49, 37.49]

 4 Respiratory rate at 20 min115Mean Difference (IV, Fixed, 95% CI)6.40 [-1.38, 14.18]

 5 Oxygen saturation at 20 min115Mean Difference (IV, Fixed, 95% CI)-0.40 [-1.68, 0.88]

 
Comparison 2. Heliox versus placebo or no treatment

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Need for rescue adrenaline147Odds Ratio (M-H, Fixed, 95% CI)0.16 [0.02, 1.46]

 2 Taussig croup score at 60 min147Mean Difference (IV, Fixed, 95% CI)-1.12 [-2.06, -0.18]

 3 Taussig croup score at 120 min147Mean Difference (IV, Fixed, 95% CI)-0.71 [-1.72, 0.30]

 4 Respiratory rate at 60 min147Mean Difference (IV, Fixed, 95% CI)-4.94 [-9.66, -0.22]

 5 Respiratory rate at 120 min147Mean Difference (IV, Fixed, 95% CI)-3.17 [-7.83, 1.49]

 6 Number of children admitted147Odds Ratio (M-H, Fixed, 95% CI)0.46 [0.04, 5.41]

 7 Number of re-presentations to ED147Odds Ratio (M-H, Fixed, 95% CI)0.95 [0.12, 7.41]

 
Table 1. Summary of studies table

AuthorsNumber of participantsCroup severityPre-randomisation treatmentIntervention and duration of administrationComparison and duration of administrationOutcome time points

Terregino 199815MildNoneHumidified helium-oxygen mixture 70%/30% over 20 minutesHumidified oxygen 30% over 20 minutesImmediate - 20 minutes post-treatment

Weber 200129Moderate to severeIntramuscular dexamethasone 0.6 mg/kgHelium-oxygen inhalation (70%/30%) and up to 2 normal saline nebulisers over 3 hoursOxygen (100%) and up to 2 doses of nebulised racaemic epinephrine over 3 hoursImmediate - 30 minutes, medium - 60 and 90 minutes, long-term 120, 180 and 240 minutes

Pardillo 200947ModerateOral dexamethasone 0.3 mg/kgHelium-oxygen 70%/30% over 1 hourNo treatmentImmediate - no, medium - 60 minutes, long-term - 120 minutes