The effectiveness of glucocorticoids in treating croup: meta-analysis
BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7210.595 (Published 04 September 1999) Cite this as: BMJ 1999;319:595
Data supplement
Table A Characteristics of randomised controlled trials of treatments for croup included in the meta-analysis
Trial
No of patients
Setting
Intervention
Control
Outcomes
Jadad score*
Allocation Concealment†
Cruz 1995w1
45
Accident and emergency
Intramuscular dexamethasone 0.6 mg/kg
Placebo
Clinical improvement, visits to the doctor, readmissions
2
1
Eden 1964w2
50
Hospital
Intramuscular methylprednisolone
4 mg/kg/day
Placebo
Clinical improvement, use of mist tent and antibiotics
3
3
Eden 1967w3
50
Hospital
Intramuscular dexamethasone 0.4 mg/kg/day
Placebo
Stridor, dyspnoea, retractions, and cyanosis
3
3
Fitzgerald 1996w4
67
Hospital
Nebulised budesonide 2 mg
L-epinephrine 4 mg
Modified Westley croup score, use of epinephrine and steroids, length of hospital stay
3
2
Geelhoed 1995w5
80
Accident and emergency
Nebulised budesonide 2 mg
Oral dexamethasone 0.6 mg/kg
Placebo
Stridor and retractions, use of epinephrine, length of stay in observation unit
3
3
Geelhoed 1995aw6
60
Accident and emergency
Oral dexamethasone 0.6 mg/kg
Oral dexamethasone 0.3 mg/kg
Stridor and retractions, use of epinephrine, length of stay in observation unit
3
3
Geelhoed 1995bw6
60
Accident and emergency
Oral dexamethasone 0.3 mg/kg
Oral dexamethasone 0.15 mg/kg
Proportion hospitalised in 24 hours
Geelhoed 1996w7
100
Accident and emergency
Oral dexamethasone 0.15 mg/kg
Placebo
Return to accident and emergency department for symptoms of croup
2
3
Godden 1997w8
87
Hospital
Nebulised budesonide 2 mg initially, then 1 mg every 12 hours during hospitalization
Placebo
Modified Westley croup score, use of epinephrine and intubation, length of stay
4
3
Husby 1993w9
37
Hospital
Nebulised budesonide 1mg/dose for two doses 30 minutes apart
Placebo
Modified Westley croup score, use of antibiotics
3
3
James 1969w10
88
Hospital
Intramuscular dexamethasone
4 -12 mg
Placebo
Use of mist tent or antibiotics, tracheostomy
4
3
Johnson 1996w11
55
Accident and emergency
Nebulised dexamethasone
10-20 mg
Placebo
Modified Westley croup score, admission rate
4
1
Johnson 1998w12
144
Accident and emergency
Nebulised budesonide 4 mg
Placebo
Westley croup score, use of epinephrine and mist treatment
2
1
Klassen 1998w13
198
Accident and emergency
Nebulised budesonide 2 mg Nebulised budesonide 2 mg and oral dexamethasone 0.6 mg/kg
Oral dexamethasone 0.6 mg/kg
Westley croup score, use of epinephrine and steroids, length of stay, admission rates
5
1
Klassen 1994w14
54
Accident and emergency
Nebulised budesonide 2 mg
Placebo
Westley croup score, use of epinephrine and steroids, length of stay, admission rates
5
1
Klassen 1996w15
50
Accident and emergency
Nebulised budesonide 2 mg and oral dexamethasone 0.6 mg/kg
Oral dexamethasone 0.6 mg/kg
Westley croup score, use of epinephrine and steroids, length of stay, admission rates
5
1
Koren 1983w16
78
Hospital
Intramuscular dexamethasone 0.6 mg/kg
Placebo
Respiratory rate
2
3
Kuusela 1988w17
72
Hospital
Intramuscular dexamethasone 0.6 mg/kg,
Intramuscular dexamethasone 0.6 mg/kg, and
L-epinephrine 2.25% 0.25 ml/kg
L-epinephrine 2.25% 0.25 ml/kg
Dyspnoea and cough, length of stay
3
1
Leipzig 1979w18
30
Hospital
Intramuscular dexamethasone
0.3 mg/kg/dose for two doses
Placebo
Stridor, cyanosis, retractions, respiratory rate, heart rate Use of epinephrine and intubation Length of stay
3
3
Martinez 1993w19
66
Hospital
L-epinephrine,
L-epinephrine and intramuscular dexamethasone 0.5 mg/kg, intramuscular dexamethasone 0.5 mg/kg
Placebo
Stridor, dyspnoea, cough, cyanosis, use of mist treatment
3
1
Massicotte 1973w20
42
Hospital
Intravenous methylprednisolone 4 mg at 0, 4, and 8 hours
Placebo
Clinical improvement, use of antibiotics and tracheostomy
4
1
Muhlendahl 1982w21
406
Hospital
Oral dexamethasone 6 mg
Placebo
Westley croup score, clinical improvement, tracheostomy, length of stay
2
3
Skowron 1966w22
200
Hospital
Subcutaneous dexamethasone
4 or 6 mg
Placebo
Use of mist treatment, antibiotics, tracheostomy
2
3
Super 1989w23
29
Hospital
Intramuscular dexamethasone 0.6 mg/kg
Placebo
Westley croup score, clinical improvement, use of epinephrine, steroids, mist treatment, length of stay
5
1
Tibballs 1992w24
73
Intensive care unit (intubated patients)
Nasogastric prednisolone
2 mg/kg/day until 24 hours after extubation
Placebo
Length of intubation reintubation rate
4
1
*Five point scale.
†Scored as 1=adequate, 2=inadequate, 3=unclear.
References:
w1 Cruz MN, Stewart G, Rosenberg N. Use of dexamethasone in the outpatient management of acute laryngotracheitis. Pediatrics 1995;96:220-3.
w2 Eden AN, Larkin VP. Corticosteroid treatment of croup. Pediatrics 1964;33:768-9.
w3 Eden AN, Kaufman A, Yu R. Corticosteroids and croup: controlled double-blind study. JAMA 1967;200:403-4.
w4 Fitzgerald D, Mellis C, Johnson M, Allen H, Cooper P, Van Asperen P. Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup. Pediatrics 1996;97:722-5.
w5 Geelhoed GC, Macdonald WB. Oral and inhaled steroids in croup: a randomized, placebo-controlled trial. Pediatr Pulmonol 1995;20:355-61.
w6 Geelhoed GC, Macdonald WB. Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg. Pediatr Pulmonol 1995;20:362-8.
w7 Geelhoed GC, Turner J, Macdonald WB. Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial. BMJ 1996;313:140-2.
w8 Godden CW, Campbell MJ, Hussey M, Cogswell JJ. Double blind placebo controlled trial of nebulised budesonide for croup. Arch Dis Child 1997;76:155-8.
w9 Husby S, Agertoft L, Mortensen S, Pedersen S. Treatment of croup with nebulised steroid (budesonide): a double blind, placebo controlled study. Arch Dis Child 1993;68:352-5.
w10 James JA. Dexamethasone in croup: a controlled study. Am J Dis Child 1969;117:511-6.
w11 Johnson DW, Schuh S, Koren G, Jaffe DM. Outpatient treatment of croup with nebulized dexamethasone. Arch Pediatr Adolesc Med 1996;150:349-55.
w12 Johnson DW, Jacobson S, Edney PC, Hadfield P, Mundy ME, Schuh S. A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. N Engl J Med 1998;339:498-503.
w13 Klassen TP, Craig WR, Moher D, Osmond MH, Pasterkamp H, Sutcliffe T, et al. Nebulized budesonide and oral dexamethasone for treatment of croup: a randomized controlled trial. JAMA 1998;279:1629-32.
w14 Klassen TP, Feldman ME, Watters LK, Sutcliffe T, Rowe PC. Nebulized budesonide for children with mild-to-moderate croup. N Engl J Med 1994;331:285-9.
w15 Klassen TP, Watters LK, Feldman ME, Sutcliffe T, Rowe PC. The efficacy of budesonide in dexamethasone-treated outpatients with croup. Pediatrics 1996;97:463-6.
w16 Koren GF. Corticosteroid treatment of laryngotracheitis v spasmodic croup in children. Am J Dis Child 1983;137:941-44.
w17 Kuusela AL, Vesikari T. A randomized double-blind, placebo-controlled trial of dexamethasone and racemic epinephrine in the treatment of croup. Acta Paediatr Scand 1988;77:99-104.
w18 Leipzig B, Oski FA, Cummings CW, Stockman JA, Swender P. A prospective randomized study to determine the efficacy of steroids in treatment of croup. J Pediatr 1979;94:194-6.
w19 Martinez Fernandez A, Sanchez Gonzalez E, Rica Etxebarria I, Echaniz Urcelay I, Alonso Diez M, Vilella Ciriza M, et al. [Randomized double-blind study of treatment of croup with adrenaline and/or dexamethasone in children]. Anales Españoles de Pediatría1993;38:29-32. (In Spanish.)
w20 Massicote P, Tetreault L. [Evaluation of methyl-prednisolone in the treatment of acute laryngitis in children]. Union Med Can 1973;102:2064-72. (In French.)
w21 Von Muhlendahl KE, Kahn D, Spohr HL, Dressler F. Steroid treatment in pseudo-croup. Helv Paediatr Acta 1982;37:431-6.
w22 Skowron PN, Turner JA, McNaughton GA. The use of corticosteroid (dexamethasone) in the treatment of acute laryngotracheitis. Can Med Assoc J 1966;94:528-31.
w23 Super DM, Cartelli NA, Brooks LJ, Lembo RM, Kumar ML. A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis. J Pediatr 1989;115:323-9.
w24 Tibballs J, Shann FA, Landau LI. Placebo-controlled trial of prednisolone in children intubated for croup. Lancet 1992;340:745-8.
Appendix 1
Literature searchTwo computerised bibliographic databases were searched to find all publications examining and exploding glucocorticoid therapy (and each one of the names of the corticosteroids) of croup. MEDLINE database from January 1966 through August 1997 and Excerpta Medica database from January 1974 through August 1997. Only randomised controlled trials were selected using the Cochrane Collaborative Review Group search strategy (Dickersin 1994), in anywhere of the manuscript. Studies published in any language were included. Relevant studies were identified through handsearching by the Acute Respiratory Infection Review Group. The Clinical Trials Cochrane database was also reviewed <Cochrane 1997>. The number of unique references retrieved were 363
Database: Medline <1966 to August 1997>.
Set Search 1 exp glucocorticoids/ 2 hydrocortisone.tw,rn. 3 hydroxypregnenolone.tw,rn. 4 pregnenolone.tw,rn. 5 tetrahydrocortisol.tw,rn. 6 hydrocortisone.tw,rn. 7 cortodoxone.tw,rn. 8 cortisone.tw,rn. 9 corticosterone.tw,rn. 10 hydroxycorticosteroids.tw,rn. 11 glucocorticoids.tw,rn. 12 exp glucocorticoids, synthetic/ 13 triamcinolone.tw,rn. 14 prednisone.tw,rn. 15 prednisolone.tw,rn. 16 paramethasone.tw,rn. 17 methylprednisolone.tw,rn. 18 methylprednisolone hemisuccinate.tw,rn. 19 dexamethasone.tw,rn. 20 clobetasol.tw,rn. 21 beclomethasone.tw,rn. 22 betamethasone.tw,rn. 23 glucocorticoids, synthetic.rn. 24 glucocorticoid$.tw. 25 exp glucocorticoids, topical/ 26 pregnenediones/ 27 budesonide.tw,rn. 28 corticosteroid$.tw. 29 or/1-28 30 croup/ or croup.tw. 31 laryngotracheitis.tw. 32 or/30-31 33 29 and 32 34 exp laryngitis/ 35 29 and 34...192 Database: Embase <1980 to Wk 32 1997>
Set Search 1 exp glucocorticoid/ 2 hydrocortisone.tw,hw,tn,rn. 3 hydroxypregnenolone.tw,hw,tn,rn. 4 pregnenolone.tw,hw,tn,rn. 5 tetrahydrocortisol.tw,hw,tn,rn. 6 hydrocortisone.tw,hw,tn,rn. 7 cortodoxone.tw,hw,tn,rn. 8 cortisone.tw,hw,tn,rn. 9 corticosterone.tw,hw,tn,rn. 10 hydroxycorticosteroids.tw,hw,tn,rn. 11 glucocorticoid$.tw,hw,tn,rn. 12 triamcinolone.tw,hw,tn,rn. 13 prednisone.tw,hw,tn,rn. 14 prednisolone.tw,hw,tn,rn. 15 paramethasone.tw,hw,tn,rn. 16 methylprednisolone.tw,hw,tn,rn. 17 dexamethasone.tw,hw,tn,rn. 18 clobetasol.tw,hw,tn,rn. 19 beclomethasone.tw,hw,tn,rn. 20 betamethasone.tw,hw,tn,rn. 21 pregnenedione$.tw,hw,tn,rn. 22 budesonide.tw,hw,tn,rn. 23 corticosteroid$.tw.,hw,tn,rn. 24 or/1-23 25 exp laryngitis/ 26 laryngitis.tw,hw. 27 croup.tw,hw. 28 laryngothracheitis.tw,hw. 29 pseudocroup.tw,hw. 30 or/25-29 31 24 and 30...236 A Cochrane search was made in August 1997. Thirty references were retrieved. The total number of references retrieved from the three data bases were 458. The duplicates were 95. The clean and merge database was composed by 363 unique articles.
To determine the studies to be assessed two independent observers (AS,TK) reviewed the title, methods section and keywords of every article's reference. With this method 84 articles were collected to be assessed. A set of 10 additional references were identified. Two additional unpublished studies were achieved. After exclude 43 reviews articles finally we got a set of 53 potentially relevant articles.
Letters to the authors were written in order to get additional references, or obtain dispersion measures not reported in the original trials.
Two different observers (AS, TK) went through these references using a relevance form with 4 items: 1. diagnosis of croup 2. Treatment with glucocorticoids versus placebo or any other active treatment 3. Clinical outcome measure 4. Randomisation. All the studies included in the systematic review should fulfilled the 4 items.
This information appears as supplied by the authors
Appendix 2
List of randomised controlled trials included in figure 1: pooled effect sizes of glucocorticoid treatment for croup versus placebo.Budesonide versus placebo at 6 hours
Husby 93,w9 Godden 97,w8 Klassen 94,w14 Geelhoed 95,w5 and Johnson 98.w12
Budesonide versus placebo at 12 hours
Godden 97w8 and Geelhoed 95.w5
Dexamethasone versus placebo at 6 hours
Cruz 95,w1 Kuusela 88,w17 von Mulhlendahl 82,w21 Koren 83,w16 Johnson 96,w11 Martinez 93,w19 Geelhoed 95,w6 and Johnson 98.w12
Dexamethasone versus placebo at 12 hours
Kuusela 88,w17 von Mulhlendahl 82,w21 Martinez 93,w19 Super 89,w23 and Geelhoed 95.w6
Dexamethasone versus placebo at 24 hours
von Mulhlendahl 82,w21 Martinez 93,w19 Super 89,w23 and Leipiz 79.w18
Budesonide or dexamethasone versus placebo at 6 hours
Husby 93,w9 Godden 97,w8 Klassen 94,w14 Geelhoed 95,w5 Johnson 98,w12 Cruz 95,w1 Kuusela 88,w17 Mulhlendahl 82,w21 Koren 83,w16 Johnson 96,w11 Martinez 93,w19 Geelhoed 95,w6 and Johnson 98.w12
Budesonide or dexamethasone versus placebo at 12 hours
Godden 97,w8 Geelhoed 95,w5 Kuusela 88,w17 von Mulhlendahl 82,w21 Martinez 93,w19 Super 89,w23 and Geelhoed 95.w6
Budesonide or dexamethasone versus placebo at 24 hours
Godden 97,w8 von Mulhlendahl 82,w21 Martinez 93,w19 Super 89,w23 and Leipiz 79.w18
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