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Meta-Analysis
. 2018 Aug 22;8(8):CD001955.
doi: 10.1002/14651858.CD001955.pub4.

Glucocorticoids for Croup in Children

Affiliations
Free PMC article
Meta-Analysis

Glucocorticoids for Croup in Children

Allison Gates et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011.

Objectives: To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies.

Selection criteria: We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events.

Data collection and analysis: One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach.

Main results: We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children.

Authors' conclusions: Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.

Conflict of interest statement

Allison Gates: None known. Michelle Gates: None known. Ben Vandermeer: None known. Cydney Johnson: None known. Lisa Hartling: None known. David W Johnson: is an author of three of the included studies (Bjornson 2004; Johnson 1996; Johnson 1998). Terry P Klassen: is an author of four of the included studies (Bjornson 2004; Klassen 1994; Klassen 1996; Klassen 1998).

Figures

1
1
Flow diagram of study selection for the 2018 update searches. In 2014, the review authors identified 30 studies in an interim update search. The review authors included one new study, Dobrovoljac 2012, and excluded one new study, Faghihinia 2007.
2
2
Risk of bias graph: Review authors' judgements of risk of bias for each domain and overall presented as percentages across all included studies.
3
3
Risk of bias summary: Review authors' judgements of risk of bias among seven domains and overall for each included study.
4
4
Cumulative meta‐graph by year for change in croup score six hours after treatment for any glucocorticoid compared to placebo.
5
5
Cumulative meta‐graph by year for return visits or (re)admissions or both for any glucocorticoid compared to placebo.
1.1
1.1
Comparison 1 Any glucocorticoid compared to placebo, Outcome 1 Croup score (change baseline ‐ 2 hours) by score.
1.2
1.2
Comparison 1 Any glucocorticoid compared to placebo, Outcome 2 Croup score (change baseline ‐ 6 hours) by score.
1.3
1.3
Comparison 1 Any glucocorticoid compared to placebo, Outcome 3 Croup score (change baseline ‐ 12 hours) by score.
1.4
1.4
Comparison 1 Any glucocorticoid compared to placebo, Outcome 4 Croup score (change baseline ‐ 24 hours) by score.
1.5
1.5
Comparison 1 Any glucocorticoid compared to placebo, Outcome 5 Croup score (change baseline ‐ 2 hours) by inpatient/outpatient.
1.6
1.6
Comparison 1 Any glucocorticoid compared to placebo, Outcome 6 Croup score (change baseline ‐ 6 hours) by inpatient/outpatient.
1.7
1.7
Comparison 1 Any glucocorticoid compared to placebo, Outcome 7 Croup score (change baseline ‐ 24 hours) by inpatient/outpatient.
1.8
1.8
Comparison 1 Any glucocorticoid compared to placebo, Outcome 8 Croup score (change baseline ‐ 2 hours) by glucocorticoid.
1.9
1.9
Comparison 1 Any glucocorticoid compared to placebo, Outcome 9 Croup score (change baseline ‐ 6 hours) by glucocorticoid.
1.10
1.10
Comparison 1 Any glucocorticoid compared to placebo, Outcome 10 Croup score (change baseline ‐ 12 hours) by glucocorticoid.
1.11
1.11
Comparison 1 Any glucocorticoid compared to placebo, Outcome 11 Croup score (change baseline ‐ 24 hours) by glucocorticoid.
1.12
1.12
Comparison 1 Any glucocorticoid compared to placebo, Outcome 12 Return visits or (re)admissions or both by inpatient/outpatient.
1.13
1.13
Comparison 1 Any glucocorticoid compared to placebo, Outcome 13 Return visits or (re)admissions or both by glucocorticoid.
1.14
1.14
Comparison 1 Any glucocorticoid compared to placebo, Outcome 14 Return visits or (re)admissions or both by croup severity.
1.15
1.15
Comparison 1 Any glucocorticoid compared to placebo, Outcome 15 Length of stay by inpatient/outpatient.
1.16
1.16
Comparison 1 Any glucocorticoid compared to placebo, Outcome 16 Length of stay by glucocorticoid.
1.17
1.17
Comparison 1 Any glucocorticoid compared to placebo, Outcome 17 Improvement (at 2 hours) by inpatient/outpatient.
1.18
1.18
Comparison 1 Any glucocorticoid compared to placebo, Outcome 18 Improvement (at 6 hours) by inpatient/outpatient.
1.19
1.19
Comparison 1 Any glucocorticoid compared to placebo, Outcome 19 Improvement (at 12 hours) by inpatient/outpatient.
1.20
1.20
Comparison 1 Any glucocorticoid compared to placebo, Outcome 20 Improvement (at 24 hours) by inpatient/outpatient.
1.21
1.21
Comparison 1 Any glucocorticoid compared to placebo, Outcome 21 Improvement (at 6 hours) by glucocorticoid.
1.22
1.22
Comparison 1 Any glucocorticoid compared to placebo, Outcome 22 Improvement (at 12 hours) by glucocorticoid.
1.23
1.23
Comparison 1 Any glucocorticoid compared to placebo, Outcome 23 Improvement (at 24 hours) by glucocorticoid.
1.24
1.24
Comparison 1 Any glucocorticoid compared to placebo, Outcome 24 Additional treatments: antibiotics.
1.25
1.25
Comparison 1 Any glucocorticoid compared to placebo, Outcome 25 Additional treatments: epinephrine.
1.26
1.26
Comparison 1 Any glucocorticoid compared to placebo, Outcome 26 Additional treatments: intubation/tracheostomy.
1.27
1.27
Comparison 1 Any glucocorticoid compared to placebo, Outcome 27 Additional treatments: mist tent.
1.28
1.28
Comparison 1 Any glucocorticoid compared to placebo, Outcome 28 Additional treatments: supplemental glucocorticoids.
2.1
2.1
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 1 Croup score (change baseline ‐ 2 hours) by inpatient/outpatient.
2.2
2.2
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 2 Croup score (change baseline ‐ 6 hours) by inpatient/outpatient.
2.3
2.3
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 3 Croup score (change baseline ‐ 12 hours) by inpatient/outpatient.
2.4
2.4
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 4 Croup score (change baseline ‐ 24 hours) by inpatient/outpatient.
2.5
2.5
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 5 Croup score (change baseline ‐ 2 hours) by glucocorticoid.
2.6
2.6
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 6 Croup score (change baseline ‐ 12 hours) by glucocorticoid.
2.7
2.7
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 7 Croup score (change baseline ‐ 24 hours) by glucocorticoid.
2.8
2.8
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 8 Return visits or (re)admissions or both by inpatient/outpatient.
2.9
2.9
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 9 Length of stay by inpatient/outpatient.
2.10
2.10
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 10 Additional treatments: use of epinephrine.
2.11
2.11
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 11 Additional treatments: intubation/tracheostomy.
2.12
2.12
Comparison 2 Any glucocorticoid compared to epinephrine, Outcome 12 Additional treatments: supplemental glucocorticoids.
3.1
3.1
Comparison 3 Dexamethasone compared to budesonide, Outcome 1 Croup score (change baseline ‐ 6 hours) by inpatient/outpatient.
3.2
3.2
Comparison 3 Dexamethasone compared to budesonide, Outcome 2 Croup score (change baseline ‐ 12 hours) by inpatient/outpatient.
3.3
3.3
Comparison 3 Dexamethasone compared to budesonide, Outcome 3 Return visits or (re)admissions or both by inpatient/outpatient.
3.4
3.4
Comparison 3 Dexamethasone compared to budesonide, Outcome 4 Length of stay by inpatient/outpatient.
3.5
3.5
Comparison 3 Dexamethasone compared to budesonide, Outcome 5 Improvement (at 6 hours) by inpatient/outpatient.
3.6
3.6
Comparison 3 Dexamethasone compared to budesonide, Outcome 6 Additional treatments: epinephrine.
3.7
3.7
Comparison 3 Dexamethasone compared to budesonide, Outcome 7 Additional treatments: intubation/tracheostomy.
3.8
3.8
Comparison 3 Dexamethasone compared to budesonide, Outcome 8 Additional treatments: supplemental glucocorticoids.
4.1
4.1
Comparison 4 Dexamethasone compared to beclomethasone, Outcome 1 Return visits or (re)admissions or both by inpatient/outpatient.
5.1
5.1
Comparison 5 Dexamethasone compared to betamethasone, Outcome 1 Croup score (change baseline ‐ 2 hours) by inpatient/outpatient.
5.2
5.2
Comparison 5 Dexamethasone compared to betamethasone, Outcome 2 Croup score (change baseline ‐ 6 hours) by inpatient/outpatient.
5.3
5.3
Comparison 5 Dexamethasone compared to betamethasone, Outcome 3 Return visits or (re)admissions or both by inpatient/outpatient.
5.4
5.4
Comparison 5 Dexamethasone compared to betamethasone, Outcome 4 Additional treatments: use of epinephrine.
6.1
6.1
Comparison 6 Dexamethasone compared to prednisolone, Outcome 1 Croup (change baseline ‐ 6 hours) by inpatient/outpatient.
6.2
6.2
Comparison 6 Dexamethasone compared to prednisolone, Outcome 2 Return visits or (re)admissions or both by inpatient/outpatient.
6.3
6.3
Comparison 6 Dexamethasone compared to prednisolone, Outcome 3 Length of stay by inpatient/outpatient.
6.4
6.4
Comparison 6 Dexamethasone compared to prednisolone, Outcome 4 Additional treatments: epinephrine.
6.5
6.5
Comparison 6 Dexamethasone compared to prednisolone, Outcome 5 Additional treatments: supplemental glucocorticoids.
7.1
7.1
Comparison 7 Budesonide and dexamethasone compared to dexamethasone, Outcome 1 Croup score (change baseline ‐ 6 hours) by inpatient/outpatient.
7.2
7.2
Comparison 7 Budesonide and dexamethasone compared to dexamethasone, Outcome 2 Return visits or (re)admissions or both by inpatient/outpatient.
7.3
7.3
Comparison 7 Budesonide and dexamethasone compared to dexamethasone, Outcome 3 Length of stay by inpatient/outpatient.
7.4
7.4
Comparison 7 Budesonide and dexamethasone compared to dexamethasone, Outcome 4 Improvement (at 6 hours) by inpatient/outpatient.
7.5
7.5
Comparison 7 Budesonide and dexamethasone compared to dexamethasone, Outcome 5 Additional treatments: epinephrine.
7.6
7.6
Comparison 7 Budesonide and dexamethasone compared to dexamethasone, Outcome 6 Additional treatments: mist tent.
7.7
7.7
Comparison 7 Budesonide and dexamethasone compared to dexamethasone, Outcome 7 Additional treatments: supplemental glucocorticoids.
8.1
8.1
Comparison 8 Budesonide and dexamethasone compared to budesonide, Outcome 1 Croup score (change baseline ‐ 6 hours) by inpatient/outpatient.
8.2
8.2
Comparison 8 Budesonide and dexamethasone compared to budesonide, Outcome 2 Return visits or (re)admissions or both by inpatient/outpatient.
8.3
8.3
Comparison 8 Budesonide and dexamethasone compared to budesonide, Outcome 3 Length of stay by inpatient/outpatient.
8.4
8.4
Comparison 8 Budesonide and dexamethasone compared to budesonide, Outcome 4 Improvement (at 6 hours) by inpatient/outpatient.
8.5
8.5
Comparison 8 Budesonide and dexamethasone compared to budesonide, Outcome 5 Additional treatments: epinephrine.
8.6
8.6
Comparison 8 Budesonide and dexamethasone compared to budesonide, Outcome 6 Additional treatments: supplemental glucocorticoids.
9.1
9.1
Comparison 9 Oral compared to intramuscular dexamethasone, Outcome 1 Return visits or (re)admissions or both by inpatient/outpatient.
9.2
9.2
Comparison 9 Oral compared to intramuscular dexamethasone, Outcome 2 Improvement (at 24 hours) by inpatient/outpatient.
9.3
9.3
Comparison 9 Oral compared to intramuscular dexamethasone, Outcome 3 Additional treatments: antibiotics.
9.4
9.4
Comparison 9 Oral compared to intramuscular dexamethasone, Outcome 4 Additional treatments: epinephrine.
9.5
9.5
Comparison 9 Oral compared to intramuscular dexamethasone, Outcome 5 Additional treatments: mist tent.
9.6
9.6
Comparison 9 Oral compared to intramuscular dexamethasone, Outcome 6 Additional treatments: supplemental glucocorticoids.
10.1
10.1
Comparison 10 Oral compared to nebulised dexamethasone, Outcome 1 Return visits or (re)admissions or both by inpatient/outpatient.
11.1
11.1
Comparison 11 Dexamethasone 0.30 mg/kg compared to 0.15 mg/kg, Outcome 1 Return visits or (re)admissions or both by inpatient/outpatient.
11.2
11.2
Comparison 11 Dexamethasone 0.30 mg/kg compared to 0.15 mg/kg, Outcome 2 Additional treatments: epinephrine.
11.3
11.3
Comparison 11 Dexamethasone 0.30 mg/kg compared to 0.15 mg/kg, Outcome 3 Additional treatments: supplemental glucocorticoids.
12.1
12.1
Comparison 12 Dexamethasone 0.60 mg/kg compared to 0.30 mg/kg, Outcome 1 Return visits or (re)admissions or both by inpatient/outpatient.
12.2
12.2
Comparison 12 Dexamethasone 0.60 mg/kg compared to 0.30 mg/kg, Outcome 2 Additional treatments: epinephrine.
12.3
12.3
Comparison 12 Dexamethasone 0.60 mg/kg compared to 0.30 mg/kg, Outcome 3 Additional treatments: supplemental glucocorticoids.
13.1
13.1
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 1 Croup score (change baseline ‐ 2 hours) by inpatient/outpatient.
13.2
13.2
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 2 Croup score (change baseline ‐ 6 hours) by inpatient/outpatient.
13.3
13.3
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 3 Croup score (change baseline ‐ 12 hours) by inpatient/outpatient.
13.4
13.4
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 4 Croup score (change baseline ‐ 24 hours) by inpatient/outpatient.
13.5
13.5
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 5 Return visits or (re)admissions or both by inpatient/outpatient.
13.6
13.6
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 6 Length of stay by inpatient/outpatient.
13.7
13.7
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 7 Additional treatments: epinephrine.
13.8
13.8
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 8 Additional treatments: intubation/tracheotomy.
13.9
13.9
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 9 Additional treatments: mist tent.
13.10
13.10
Comparison 13 Dexamethasone 0.60 mg/kg compared to 0.15 mg/kg, Outcome 10 Additional treatments: supplemental glucocorticoids.

Update of

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    Russell KF, Liang Y, O'Gorman K, Johnson DW, Klassen TP. Russell KF, et al. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001955. doi: 10.1002/14651858.CD001955.pub3. Cochrane Database Syst Rev. 2011. PMID: 21249651 Updated. Review.

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