Clinical Review & Education

JAMA Pediatrics | JAMA Pediatrics Clinical Evidence Synopsis

Glucocorticoids for Croup in Children

Allison Gates, PhD; David W. Johnson, MD; Terry P. Klassen, MD

CLINICAL QUESTION For children with croup, do glucocorticoids reduce clinical symptoms,
minimize return visits and/or (re)admissions to the hospital, shorten lengths of stay, or reduce
the need for additional treatments?

BOTTOM LINE Glucocorticoids reduce symptoms of croup at 2 hours and for at least 24 hours,
reduce return visits to care, and shorten hospital stays by about 15 hours. Serious adverse
events are infrequent.

Introduction ostomy (RD, 0; 95% CI, −0.01 to 0.01; 11 trials; 1090 children).
Croup, a common cause of upper airway obstruction in children, Thirteen trials (50%) that compared glucocorticoids with placebo
poses a large burden on health care systems. This article summa- collected adverse events data. Four trials reported rare occur-
rizes a Cochrane systematic review 1 of glucocorticoids for rences of secondary infections (eg, pneumonia, otitis media).
croup in children published in 19992,3 and updated in 20044 and Other adverse effects were neither severe nor frequent.
2011.5
In 2018, an update was undertaken to incorporate new evi-
dence, add outcomes (eg, any adverse events, 2-hour change in Discussion
croup score, 2-hour patient improvement), and incorporate Glucocorticoids are indicated for croup of any severity in inpatient
evaluations of risk of bias and certainty of evidence. Included and outpatient settings; evidence of their beneficial effects is stable.
were randomized clinical trials of participants age 0 to 18 years
that compared 1 or more glucocorticoids with placebo or another
active pharmacologic agent. Three databases and 2 trial registers
were searched and 5 new trials (which included 330 children)
were added.
Evidence Profile

No. of randomized clinical trials: 43

Summary of Findings
Of the 26 trials that compared any glucocorticoid with placebo,
23 (88%) studied dexamethasone (0.6 mg/kg taken orally; range,
0.15-0.6 mg/kg) or budesonide (2 mg nebulized; range, 2-4 mg).
Treatment with glucocorticoids resulted in greater reductions in
clinical croup scores after 2 hours (standardized mean difference
[SMD], −0.65; 95% CI, −1.13 to −0.18; 7 trials; 426 children;
moderate-certainty evidence). The effect lasted at least 24 hours
(SMD, −0.86; 95% CI, −1.4 to −0.31; 8 trials; 351 children; low-
certainty evidence) (Table). Compared with placebo, glucocorti-
coids reduced the rate of return visits and/or (re)admissions to
the hospital (risk ratio, 0.52; 95% CI, 0.36-0.75; 10 trials; 1679
children; moderate-certainty evidence) (Table). The number
needed to treat for an additional beneficial outcome was 7 chil-
dren (95% CI, 5-12). Glucocorticoids reduced the length of stay by
an average of 15 hours (mean difference, −14.90; 95% CI, −23.58
to −6.22; 8 trials; 476 children). There was no significant differ-
ence between children provided placebos and those treated with
glucocorticoids in the use of antibiotics (relative difference [RD],
0; 95% CI, −0.04 to 0.04; 3 trials; 202 children), epinephrine
(RD, −0.03; 95% CI, −0.08 to 0.01; 9 trials; 709 children), supple-
mental glucocorticoids (risk ratio, 0.61; 95% CI, 0.36-1.03; 6 trials;
305 children), or a mist tent (RD, −0.20; 95% CI, −0.87 to
0.47; 2 trials; 84 children), nor in the rate of intubation or trache-
Study years: Published: 1964 to 2013; literature search: current to
April 3, 2018
No. of participants: 4565 children
Male: Median, 69% (range, 50%-80%)
Race/ethnicity: Not reported
Mean age: 15 to 41 months (range of means across studies)
Setting: Inpatients (49%) and outpatients (51%, emergency
departments and physicians’ offices)
Countries: Australia, United States, Canada, Denmark, Israel,
Turkey, England, Finland, Germany, Greece, Iran, Netherlands,
Saudi Arabia, Spain, Thailand
Comparisons: Any glucocorticoid vs placebo, any glucocorticoid vs
epinephrine, dexamethasone vs budesonide, dexamethasone vs
beclomethasone, dexamethasone vs prednisolone, dexametha-
sone and budesonide vs dexamethasone, dexamethasone and
budesonide vs budesonide, oral vs intramuscular dexamethasone,
oral vs nebulized dexamethasone, 0.30 mg/kg vs 0.15 mg/kg
dexamethasone, 0.60 mg/kg vs 0.30 mg/kg dexamethasone,
0.60 mg/kg vs 0.15 mg/kg dexamethasone
Primary outcomes: Change in croup score (at 2, 6, 12, and
24 hours), return visits, and/or (re)admissions to the hospital
Secondary outcomes: Length of stay in the hospital, patient im-
provement (at 2, 6, 12, and 24 hours), additional treatments, and
any adverse events

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 Clinical Review & Education JAMA Pediatrics Clinical Evidence Synopsis

Table. Summary of Findings for Any Glucocorticoid Compared With Placebo for Croup Abbreviations: GRADE, Grading of
Recommendations Assessment,
No. of Relative Certainty of Development, and Evaluation;
Participants Anticipated Absolute Effectsa (95% CI) Effect the Evidence
NA, not applicable; RCT, randomized
(Studies) Outcomes Placebo Any Glucocorticoid (95% CI) (GRADE)b Commentsc
clinical trial; RR, risk ratio.
426 Change in croup Change in croup Change in croup NA Moderate An SD
a
(7 RCTs) score score, mean, score, mean (SD): I2 = 81% of 0.65 The risk in the intervention group
Assessed with range: −1.50 to 0.65 more (1.13 represents a (and its 95% CI) is based on the
different scores in −0.81 more to 0.18 more) moderate assumed risk in the comparison
different studies difference
between group and the relative effect of the
Lower scores mean intervention (and its 95% CI).
fewer symptoms groups
b
(follow-up, 2 h) GRADE working group grades of
959 Change in croup Change in croup The mean change in NA Moderate An SD evidence: (1) high certainty: we are
(11 RCTs) score score, mean, croup score was 0.76 I2 = 83% of 0.76 very confident that the true effect is
Assessed with range: −3.23 to SDs more (1.12 more represents a close to that of the estimate of the
different scores in −0.65 to 0.40 more) large effect; (2) moderate certainty: we
different studies difference
between are moderately confident in the
Lower scores mean effect estimate; the true effect is
fewer symptoms groups
(follow-up, 6 h) likely to be close to the estimate of
571 Change in croup Change in croup Change in croup NA Moderate the effect, but there is a possibility
An SD
(8 RCTs) score score, mean, score, mean (SD): I2 = 86% of 1.03 that it is substantially different;
Assessed with range: −7.62 to 1.03 more (1.53 represents (3) low certainty: our confidence in
different scores in −1.00 more to 0.53 more) a large the effect estimate is limited; the
different studies difference true effect may be substantially
Lower scores mean between
groups different from the estimate of the
fewer symptoms effect; and (4) very low certainty:
(follow-up, 12 h)
we have very little confidence in the
351 Change in croup Change in croup The mean change in NA Low An SD effect estimate; the true effect is
(8 RCTs) score score, mean. croup score was 0.86 I2 = 81% of 0.86
range: −2.56 to SDs more (1.40 more represents a likely to be substantially different
Assessed with
different scores in −1.05 to 0.31 more) large from the estimate of effect.
different studies difference c
We used the Cohen interpretation
Lower scores mean between
groups of effect sizes to determine the
fewer symptoms magnitude of the difference
(follow-up, 24 h)
between groups (0.2 represents a
1679 Return visits and/or Study population RR, 0.52 Moderate NA small effect, 0.5 represents a
(10 RCTs) (re)admissions 204 per 1000 106 per 1000 (0.36-0.75) I2 = 52%
medium effect, and 0.8 represents
(74-153) a large effect).

Dexamethasone is the mainstay of treatment for croup6 and evi-
dence shows nebulized budesonide is an effective alternative. Evi-
dence for the effects of other glucocorticoids is limited.
Limitations
Most included studies (42 of 43 [98%]) were at unclear or high
risk of bias, but the certainty of evidence was rarely downgraded
because of risk of bias. Uncertainty remains for the optimal
type, dose, and mode of administration of glucocorticoids for
croup.
Comparison of Findings With Current Guidelines
Current guidance recommends that glucocorticoids be adminis-
tered to children with croup of any severity.7 Our findings are con-
sistent with this guidance.
Areas in Need of Future Study
Trials comparing dexamethasone administered in different
ways and different doses of dexamethasone and budesonide are
warranted to inform clinical practice. Trials that compare 1
and multiple days of glucocorticoid treatment may be of interest.

ARTICLE INFORMATION
Author Affiliations: Alberta Research Centre for
Health Evidence, Department of Pediatrics, University
of Alberta, Edmonton, Alberta, Canada (Gates);
Departments of Pediatrics, Emergency Medicine,
and Physiology and Pharmacology, Cumming
School of Medicine, the Alberta Children’s Hospital
Research Institute, University of Calgary, Calgary,
Alberta, Canada (Johnson); George & Fay Yee
Centre for Health Care Innovation, Children’s
Hospital Research Institute of Manitoba, Depart-
ment of Pediatrics and Child Health, University of
Manitoba, Winnipeg, Manitoba, Canada (Klassen).
Corresponding Author: Terry P. Klassen, MD,
Children’s Hospital Research Institute of Manitoba,
513-715 McDermot Ave, Winnipeg, Manitoba R3E
3P4, Canada (tklassen@chrim.ca).
Published Online: April 29, 2019.
doi:10.1001/jamapediatrics.2019.0834
Conflict of Interest Disclosures: Drs Klassen and
Johnson were authors on 4 and 3 of the trials
included in the systematic review, respectively. Dr
Klassen receives grant support from Translating
Emergency Knowledge for Kids (TREKK). No other
disclosures are reported.
Additional Contributions: We thank Michelle
Gates, PhD, Lisa Hartling, PhD, Ben Vandermeer,
MSc, and Cydney Johnson, BSc, University of
Alberta, for helping to complete the systematic
review. We thank Robin Featherstone, MLIS, for
implementing the update searches; Gabrielle
Zimmermann, PhD, Devonne Brandys, MSc, and
Bita Mesgarpour, MD, for translating the
non-English studies; and Jennifer Pillay, MSc, for
assisting with GRADE (University of Alberta).
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Glucocorticoids for croup in children. Cochrane
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