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Cochrane Database of Systematic Reviews

Intravenous magnesium sulfate for treating children with acute asthma in the emergency department

Information

DOI:
https://doi.org/10.1002/14651858.CD011050.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 29 April 2016see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Airways Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Benedict Griffiths

    Evelina London Children’s Hospital, St Thomas' Hospital, London, UK

  • Kayleigh M Kew

    Correspondence to: Population Health Research Institute, St George's, University of London, London, UK

    [email protected]

Contributions of authors

Ben Griffiths wrote the background and managed the clinical implications of the methods. Kayleigh Kew wrote the methods. Review authors extracted the data independently, and constructed the analyses and assessed the evidence together. Both review authors contributed to and approved the final draft.

Sources of support

Internal sources

  • Kayleigh Kew, UK.

    St George's, University of London

External sources

  • NIHR, UK.

    This project was supported by the National Institute for Health Research, via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to the Airways Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS, or the Department of Health.

Declarations of interest

Benedict Griffiths: None known

Kayleigh Kew: None known

Acknowledgements

Chris Cates was the Editor for this review and commented critically on the review. Elizabeth Stovold designed the search strategy.

We would like to thank Clare Michell and Liza Kirtchuk for contributing to the design of the review question, which was written alongside the adult version of this review.

The Background and Methods sections of this review are based on a standard template used by Cochrane Airways.

Version history

Published

Title

Stage

Authors

Version

2016 Apr 29

Intravenous magnesium sulfate for treating children with acute asthma in the emergency department

Review

Benedict Griffiths, Kayleigh M Kew

https://doi.org/10.1002/14651858.CD011050.pub2

2014 Apr 25

Intravenous magnesium sulfate for treating children with acute asthma in the emergency department

Protocol

Benedict Griffiths, Kayleigh M Kew, Clare I Michell, Liza Kirtchuk

https://doi.org/10.1002/14651858.CD011050

Differences between protocol and review

We were not able to pool more than 10 studies, and so could not create and examine a funnel plot to explore possible small‐study and publication biases. Since there were only three studies in the primary analysis (and fewer in the secondary), we did not consider the planned subgroup and sensitivity analyses to be justified.

We did not use an independent assessor as planned to classify the study populations as having moderate, severe, and life‐threatening exacerbations because we were not able to perform the associated subgroup analysis. Instead, the classification was made for descriptive purposes only by one of the review authors (BG). If additional studies allow the subgroup analysis to be undertaken in a future update of this review, this will be done by an assessor blinded to the study results.

We did not specify 'Return to the emergency department within 48 hours' as an outcome in the protocol for this systematic review, but chose to present the results because it is related to other named outcomes which were not well reported across studies.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 IV MgSO4 versus placebo, Outcome 1 Hospital admissions.
Figures and Tables -
Analysis 1.1

Comparison 1 IV MgSO4 versus placebo, Outcome 1 Hospital admissions.

Comparison 1 IV MgSO4 versus placebo, Outcome 2 ED treatment time (minutes).
Figures and Tables -
Analysis 1.2

Comparison 1 IV MgSO4 versus placebo, Outcome 2 ED treatment time (minutes).

Comparison 1 IV MgSO4 versus placebo, Outcome 3 Return to ED within 48 hours.
Figures and Tables -
Analysis 1.3

Comparison 1 IV MgSO4 versus placebo, Outcome 3 Return to ED within 48 hours.

Comparison 1 IV MgSO4 versus placebo, Outcome 4 Hospital length of stay (hours).
Figures and Tables -
Analysis 1.4

Comparison 1 IV MgSO4 versus placebo, Outcome 4 Hospital length of stay (hours).

Summary of findings for the main comparison. MgSO4 compared to placebo for treating children with acute asthma in the emergency department

MgSO4 compared to placebo for treating children with acute asthma in the emergency department

Patient or population: children with acute asthma in the emergency department
Settings: emergency departments
Intervention: MgSO4
Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

MgSO4

Hospital admissions

767 per 1000

513 per 1000
(315 to 709)

OR 0.32
(0.14 to 0.74)

115
(3 studies)

⊕⊕⊝⊝
low1,2

MgSO4 reduced hospital admissions, but low confidence due to inconsistency and small numbers.

Random‐effects sensitivity analysis:

OR 0.18, 95% CI 0.02 to 1.59

ED treatment time (minutes)

The mean ED treatment time in the placebo group was

96 minutes

The mean ED treatment time in the intervention group was
5 minutes more

(24 less to 34 more)

27
(1 study)

⊕⊕⊝⊝

low3

No clear benefit of MgSO4.

Based on the subset of children who were discharged home, not those who were admitted

Return to ED within 48 hours

22 per 1000

9 per 1000
(0 to 186)

OR 0.4
(0.02 to 10.3)

85
(2 studies)

⊕⊕⊝⊝
low3

No clear benefit of MgSO4

Hospital length of stay (hours)

The mean hospital length of stay (hours) in the placebo group was
18.9 hours

The mean hospital length of stay (hours) in the intervention group was
5.3 hours lower
(9.46 to 1.14 lower)

47
(1 study)

⊕⊕⊝⊝
low4,5

Possible benefit of MgSO4 but based on 1 small study

4 of the planned outcomes were not reported in a way that could be meta‐analysed in any of the included studies (intensive care admissions, vital signs, spirometry, validated paediatric symptom scores, and adverse events)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ED: emergency department; OR: odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Test for heterogeneity P = 0.07, I2 = 63% (‐1 inconsistency).
2Total number of children included in analysis low with concurrent low event rate, and a sensitivity analysis using random effects seriously reduced the precision of the estimate (‐1 imprecision).
3Very imprecise estimate based on data from a single small study. 'Return to ED within 48 hours' analysis included two studies, but Ciarallo 1996 did not observe any events (‐2 imprecision).
4Only study included limiting the precision of the result (‐1 imprecision).
5Two other studies reported hospital admission but not length of hospital stay (‐1 publication bias).

Figures and Tables -
Summary of findings for the main comparison. MgSO4 compared to placebo for treating children with acute asthma in the emergency department
Table 1. Summary characteristics of included studies

Study ID

Country (centres)

Total N

Study design

Age range (yrs)

Dose (infusion)

Comedications

Ciarallo 1996

USA (2)

30

R, DB, PC

6 to 18

25 mg/kg

20 minutes

3 nebulised bronchodilators (albuterol, ipratropium bromide, or both)
IV methylprednisolone (2 mg/kg) if not yet given corticosteroids

Ciarallo 2000

USA (1)

31

R, DB, PC

6 to 18

40 mg/kg

20 minutes

3 nebulised beta‐2 adrenergic treatments

IV methylprednisolone (2 mg/kg) if not yet given corticosteroids

Devi 1997

India (1)

47

R, DB, PC

1 to 12

0.2 ml of 50%

35 minutes

Nebulised salbutamol

Oxygen, IV aminophylline, corticosteroids

Gürkan 1999

Turkey (1)

20

R, DB, PC

6 to 16

40 mg/kg

20 minutes

3 beta‐2 adrenergic nebuliser treatments

Scarfone 2000

USA (3)

54

R, DB, PC

1 to 18

75 mg/kg

20 minutes

Nebulised albuterol

Oxygen, methylprednisolone

R = randomised; DB = double‐blind; PC = placebo‐controlled

Figures and Tables -
Table 1. Summary characteristics of included studies
Table 2. Baseline characteristics

Study ID

Inclusion

Group

Age (SD)

% Male

% PEF

FEV1

Other

Classification

Ciarallo 1996

PEF < 60% predicted

(after 3 beta‐2 adrenergic nebuliser treatments)

MgSO4

10.8

46.7

43.8

33.1

RR = 35 BP = 120 SaO2 = 92

Moderate

Placebo

11.9

43.8

43.0

45.1

RR = 30 BP = 123 SaO2 = 94

Ciarallo 2000

PEF < 70% predicted

(after 3 nebulised bronchodilating treatments)

MgSO4

10.9

68.8

29.9

28.9

BP = 120, SaO2 = 92

Severe

Placebo

12.0

50.0

33.1

31.3

BP = 114, SaO2 = 92

Devi 1997

"Inadequate or poor response to 3 doses of nebulized salbutamol"

MgSO4

6.7

79.2

30.1

NR

HR = 142

Severe

Placebo

6.8

73.9

27.1

NR

HR = 138

Gürkan 1999

PEF < 60% predicted

(after 3 beta‐2 adrenergic nebuliser treatments)
"moderate to severe acute asthma exacerbation"

MgSO4

10.4

60

46.8

NR

HR = 118 BP = 118 SaO2 = 91.8

Moderate

Placebo

11.2

50

46.2

NR

HR = 120 BP = 116 SaO2 = 91.4

Scarfone 2000

"moderate to severe asthma exacerbation"

MgSO4

6.8

58

NR

NR

SaO2 = 93.9

Moderate

Placebo

4.8

47

NR

NR

SaO2 = 94.1

SD = standard deviation; % PEF = percentage predicted peak expiratory flow; FEV1 = forced expiratory volume in one second; HR = heart rate; RR = respiration rate; BP = systolic blood pressure; SaO2 = oxygen saturation; NR: not reported

Figures and Tables -
Table 2. Baseline characteristics
Comparison 1. IV MgSO4 versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Hospital admissions Show forest plot

3

115

Odds Ratio (M‐H, Fixed, 95% CI)

0.32 [0.14, 0.74]

2 ED treatment time (minutes) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3 Return to ED within 48 hours Show forest plot

2

85

Odds Ratio (M‐H, Fixed, 95% CI)

0.40 [0.02, 10.30]

4 Hospital length of stay (hours) Show forest plot

1

47

Mean Difference (IV, Fixed, 95% CI)

‐5.30 [‐9.46, ‐1.14]

Figures and Tables -
Comparison 1. IV MgSO4 versus placebo