Glucocorticoids for acute viral bronchiolitis in infants and young children - PubMed (original) (raw)

Review

Glucocorticoids for acute viral bronchiolitis in infants and young children

Ricardo M Fernandes et al. Cochrane Database Syst Rev. 2013.

Abstract

Background: Previous systematic reviews have not shown clear benefit of glucocorticoids for acute viral bronchiolitis, but their use remains considerable. Recent large trials add substantially to current evidence and suggest novel glucocorticoid-including treatment approaches.

Objectives: To review the efficacy and safety of systemic and inhaled glucocorticoids in children with acute viral bronchiolitis.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 12), MEDLINE (1950 to January week 2, 2013), EMBASE (1980 to January 2013), LILACS (1982 to January 2013), Scopus® (1823 to January 2013) and IRAN MedEx (1998 to November 2009).

Selection criteria: Randomised controlled trials (RCTs) comparing short-term systemic or inhaled glucocorticoids versus placebo or another intervention in children under 24 months with acute bronchiolitis (first episode with wheezing). Our primary outcomes were: admissions by days 1 and 7 for outpatient studies; and length of stay (LOS) for inpatient studies. Secondary outcomes included clinical severity parameters, healthcare use, pulmonary function, symptoms, quality of life and harms.

Data collection and analysis: Two authors independently extracted data on study and participant characteristics, interventions and outcomes. We assessed risk of bias and graded strength of evidence. We meta-analysed inpatient and outpatient results separately using random-effects models. We pre-specified subgroup analyses, including the combined use of bronchodilators used in a protocol.

Main results: We included 17 trials (2596 participants); three had low overall risk of bias. Baseline severity, glucocorticoid schemes, comparators and outcomes were heterogeneous. Glucocorticoids did not significantly reduce outpatient admissions by days 1 and 7 when compared to placebo (pooled risk ratios (RRs) 0.92; 95% confidence interval (CI) 0.78 to 1.08 and 0.86; 95% CI 0.7 to 1.06, respectively). There was no benefit in LOS for inpatients (mean difference -0.18 days; 95% CI -0.39 to 0.04). Unadjusted results from a large factorial low risk of bias RCT found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions by day 7 (baseline risk of admission 26%; RR 0.65; 95% CI 0.44 to 0.95; number needed to treat 11; 95% CI 7 to 76), with no differences in short-term adverse effects. No other comparisons showed relevant differences in primary outcomes.

Authors' conclusions: Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admissions or length of hospitalisation. Combined dexamethasone and epinephrine may reduce outpatient admissions, but results are exploratory and safety data limited. Future research should further assess the efficacy, harms and applicability of combined therapy.

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Conflict of interest statement

AP, HP, DJ and TK are authors of one or more RCTs included in this review. Assessment of eligibility, risk of bias and strength of evidence of these trials were performed by other review authors. The review authors declare no other real or perceived conflicts of interest.

Figures

1

1

Flow of citations through the search and screening procedures of the 2009 review and this 2012 update, studies included in the review and comparisons addressed (GC: glucocorticoids)

2

2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.* *For multi‐arm studies (Barlas 1998, Kuyucu 2004 and Plint 2009), we included one overall assessment for all trial comparisons, and two assessments for each separate comparison of glucocorticoids versus placebo (with or without protocolised bronchodilator, or with epinephrine or salbutamol).

3

3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.* *For multi‐arm studies (Barlas 1998, Kuyucu 2004 and Plint 2009), we included one overall assessment for all trial comparisons, and two assessments for each separate comparison of glucocorticoids versus placebo (with or without protocolised bronchodilator, or with epinephrine or salbutamol).

4

4

Funnel plot of comparison: 1 Steroid versus placebo, outcome: 1.1 Admissions (days 1 and 7) (outpatients) ‐ review primary outcome.

5

5

Funnel plot of comparison: 1 Steroid versus placebo, outcome: 1.2 Length of stay (inpatients) ‐ review primary outcome.

6

6

Forest plot of comparison: 1 Steroid versus placebo, outcome: 1.1 Admissions (days 1 and 7) (outpatients) ‐ review primary outcome.

7

7

Forest plot of comparison: 1 Steroid versus placebo, outcome: 1.4 Clinical scale scores (outpatients) (change from baseline data).

8

8

Forest plot of comparison: 1 Steroid versus placebo, outcome: 1.2 Length of stay (inpatients) ‐ review primary outcome.

9

9

Forest plot of comparison: 1 Glucocorticoid versus placebo, outcome: 1.6 Clinical scores (inpatients) (change from baseline data).

1.1

1.1. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 1 Admissions (days 1 and 7) (outpatients) ‐ review primary outcome.

1.2

1.2. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 2 Length of stay (inpatients) ‐ review primary outcome.

1.3

1.3. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 3 Length of stay (outpatients).

1.4

1.4. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 4 Clinical scores (outpatients).

1.5

1.5. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 5 Clinical scores (inpatients).

1.6

1.6. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 6 O2 saturation (outpatients).

1.7

1.7. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 7 O2 saturation (inpatients).

1.8

1.8. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 8 Respiratory rate (outpatients).

1.9

1.9. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 9 Respiratory rate (inpatients).

1.10

1.10. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 10 Heart rate (outpatients).

1.11

1.11. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 11 Heart rate (inpatients).

1.12

1.12. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 12 Hospital readmissions (inpatients).

1.13

1.13. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 13 Return healthcare visits (inpatients).

1.14

1.14. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 14 Return healthcare visits (outpatients).

1.15

1.15. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 15 Admissions at day 1 (outpatients) ‐ subgroup analysis protocolised use of bronchodilator.

1.16

1.16. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 16 Admissions within 7 days (outpatients) ‐ subgroup analysis protocolised use of bronchodilator.

1.17

1.17. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 17 Admissions at day 1 (outpatients) ‐ subgroup analysis age.

1.18

1.18. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 18 Admissions within 7 days (outpatients) ‐ subgroup analysis age.

1.19

1.19. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 19 Length of stay (inpatients) ‐ subgroup analysis protocolised use of bronchodilator.

1.20

1.20. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 20 Length of stay (inpatients) ‐ subgroup analysis age.

1.21

1.21. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 21 Length of stay (inpatients) ‐ subgroup analysis RSV status.

1.22

1.22. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 22 Admissions (days 1 and 7) (outpatients) ‐ sensitivity analysis with only low overall RoB.

1.23

1.23. Analysis

Comparison 1 Glucocorticoid versus placebo, Outcome 23 Length of stay (inpatients) ‐ sensitivity analysis with only low overall RoB.

2.1

2.1. Analysis

Comparison 2 Glucocorticoid and epinephrine versus placebo, Outcome 1 Admissions (days 1 and 7) (outpatients) ‐ review primary outcome.

2.2

2.2. Analysis

Comparison 2 Glucocorticoid and epinephrine versus placebo, Outcome 2 Clinical scores (outpatients).

2.3

2.3. Analysis

Comparison 2 Glucocorticoid and epinephrine versus placebo, Outcome 3 O2 saturation (outpatients).

2.4

2.4. Analysis

Comparison 2 Glucocorticoid and epinephrine versus placebo, Outcome 4 Respiratory rate (outpatients).

2.5

2.5. Analysis

Comparison 2 Glucocorticoid and epinephrine versus placebo, Outcome 5 Heart rate (outpatients).

2.6

2.6. Analysis

Comparison 2 Glucocorticoid and epinephrine versus placebo, Outcome 6 Return healthcare visits (outpatients).

3.1

3.1. Analysis

Comparison 3 Glucocorticoid and salbutamol versus placebo, Outcome 1 Admissions (day 1) (outpatients) ‐ review primary outcome.

3.2

3.2. Analysis

Comparison 3 Glucocorticoid and salbutamol versus placebo, Outcome 2 Clinical scores (outpatients).

3.3

3.3. Analysis

Comparison 3 Glucocorticoid and salbutamol versus placebo, Outcome 3 O2 saturation (outpatients).

3.4

3.4. Analysis

Comparison 3 Glucocorticoid and salbutamol versus placebo, Outcome 4 Heart rate (outpatients).

4.1

4.1. Analysis

Comparison 4 Glucocorticoid versus epinephrine, Outcome 1 Admissions (days 1 and 7) (outpatients) ‐ review primary outcome.

4.2

4.2. Analysis

Comparison 4 Glucocorticoid versus epinephrine, Outcome 2 Clinical scores (outpatients).

4.3

4.3. Analysis

Comparison 4 Glucocorticoid versus epinephrine, Outcome 3 O2 saturation (outpatients).

4.4

4.4. Analysis

Comparison 4 Glucocorticoid versus epinephrine, Outcome 4 Respiratory rate (outpatients).

4.5

4.5. Analysis

Comparison 4 Glucocorticoid versus epinephrine, Outcome 5 Heart rate (outpatients).

5.1

5.1. Analysis

Comparison 5 Glucocorticoid versus salbutamol, Outcome 1 Admissions (day 1) (outpatients) ‐ review primary outcome.

5.2

5.2. Analysis

Comparison 5 Glucocorticoid versus salbutamol, Outcome 2 Clinical scores (outpatients).

5.3

5.3. Analysis

Comparison 5 Glucocorticoid versus salbutamol, Outcome 3 O2 saturation (outpatients).

5.4

5.4. Analysis

Comparison 5 Glucocorticoid versus salbutamol, Outcome 4 Heart rate (outpatients).

6.1

6.1. Analysis

Comparison 6 Glucocorticoid and epinephrine versus salbutamol, Outcome 1 Admissions (day 1) (outpatients) ‐ review primary outcome.

6.2

6.2. Analysis

Comparison 6 Glucocorticoid and epinephrine versus salbutamol, Outcome 2 Clinical scores (outpatients).

6.3

6.3. Analysis

Comparison 6 Glucocorticoid and epinephrine versus salbutamol, Outcome 3 Respiratory rate (outpatients).

6.4

6.4. Analysis

Comparison 6 Glucocorticoid and epinephrine versus salbutamol, Outcome 4 Heart rate (outpatients).

7.1

7.1. Analysis

Comparison 7 Glucocorticoid and salbutamol versus epinephrine, Outcome 1 Admissions (day 1) (outpatients) ‐ review primary outcome.

7.2

7.2. Analysis

Comparison 7 Glucocorticoid and salbutamol versus epinephrine, Outcome 2 Clinical scores (outpatients).

7.3

7.3. Analysis

Comparison 7 Glucocorticoid and salbutamol versus epinephrine, Outcome 3 O2 saturation (outpatients).

7.4

7.4. Analysis

Comparison 7 Glucocorticoid and salbutamol versus epinephrine, Outcome 4 Respiratory rate (outpatients).

7.5

7.5. Analysis

Comparison 7 Glucocorticoid and salbutamol versus epinephrine, Outcome 5 Heart rate (outpatients).

8.1

8.1. Analysis

Comparison 8 Glucocorticoid versus glucocorticoid (prednisolone versus budesonide), Outcome 1 Admissions (day 1) (outpatients) ‐ review primary outcome.

8.2

8.2. Analysis

Comparison 8 Glucocorticoid versus glucocorticoid (prednisolone versus budesonide), Outcome 2 Clinical scores (outpatients).

8.3

8.3. Analysis

Comparison 8 Glucocorticoid versus glucocorticoid (prednisolone versus budesonide), Outcome 3 O2 saturation (outpatients).

8.4

8.4. Analysis

Comparison 8 Glucocorticoid versus glucocorticoid (prednisolone versus budesonide), Outcome 4 Heart rate (outpatients).

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