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Corticosteroides intramusculares versus orales para reducir las recaídas después del alta del servicio de urgencias para el asma aguda

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References

Referencias de los estudios incluidos en esta revisión

Al‐Wahadneh 2006 {published data only}

Al‐Wahadneh A, Jboor S, Dahabreh M. A comparison of efficacy and safety of a single dose of intramuscular dexamethasone acetate with oral prednisolone in the management of asthma exacerbations in children. Journal of the Royal Medical Services 2006;13(1):15‐8. CENTRAL

Chan 2001 {published data only}

Chan JS, Cowie RL, Lazarenko GC, Little C, Scott S, Ford GT. Comparison of intramuscular betamethasone and oral prednisone in the prevention of relapse of acute asthma. Canadian Respiratory Journal 2001;8(3):147‐52. [PUBMED: 11420590]CENTRAL

Gordon 2007 {published data only}

Gordon S, Tompkins T, Dayan PS. Randomized trial of single‐dose intramuscular dexamethasone compared with prednisolone for children with acute asthma. Pediatric Emergency Care 2007;23(8):521‐7. [DOI: 10.1097/PEC.0b013e318128f821]CENTRAL

Gries 2000 {published data only}

Gries DM, Moffitt DR, Pulos E, Carter ER. A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone to treat asthma exacerbations in young children. Journal of Pediatrics 2000;136(3):298‐303. [DOI: 10.1067/mpd.2000.103353]CENTRAL

Hoffman 1988 {published data only}

Hoffman IB, Fiel SB. Oral versus repository corticosteroid therapy in acute asthma. Chest 1988;93(1):11‐3. [PUBMED: 3275525]CENTRAL

Klig 1997 {published data only}

Klig JE, Hodge D, Rutherford MW. Symptomatic improvement following emergency department management of asthma: a pilot study of intramuscular dexamethasone versus oral prednisone. Journal of Asthma 1997;34(5):419‐25. [PUBMED: 9350159]CENTRAL

Lahn 2004 {published data only}

Lahn M, Bijur P, Gallagher EJ. Randomized clinical trial of intramuscular vs oral methylprednisolone in the treatment of asthma exacerbations following discharge from an emergency department. Chest 2004;126(2):362‐8. [DOI: 10.1378/chest.126.2.362]CENTRAL

Lee 1993 {published data only}

Lee CH, Lee CJ, Lan RS, Tsai YH, Chiang YC, Wang WJ, et al. Repository dexamethasone in the treatment of acute bronchial asthma. Changgeng Yi Xue Za Zhi [Chang Gung Medical Journal] 1993;16(1):25‐9. [PUBMED: 8490772]CENTRAL

Schuckman 1998 {published data only}

Schuckman H, DeJulius DP, Blanda M, Gerson LW, DeJulius AJ, Rajaratnam M. Comparison of intramuscular triamcinolone and oral prednisone in the out‐patient treatment of acute asthma: a randomized controlled trial. Annals of Emergency Medicine 1998;31(3):333‐8. [PUBMED: 9506490]CENTRAL

Referencias de los estudios excluidos de esta revisión

Andrews 2012 {published data only}

Andrews AL, Wong KA, Heine D, Scott RW. A cost‐effectiveness analysis of dexamethasone versus prednisone in pediatric acute asthma exacerbations. Academic Emergency Medicine 2012;19(8):943‐8. [DOI: 10.1111/j.1553‐2712.2012.01418.x]CENTRAL

Droszcz 1985 {published data only}

Droszcz W, Piotrowska B. Comparison of oral prednisolone and intramuscular depot triamcinolone in patients with severe chronic asthma. Thorax 1985;40(3):207‐8. [PUBMED: PMC460032]CENTRAL

Ducharme 2004 {published data only}

Ducharme FM, Rowe BH. Intramuscular versus oral methylprednisolone in asthma. Lancet 2004;364(9450):2000‐1. [DOI: 10.1016/S0140‐6736(04)17526‐0]CENTRAL

Green 1995 {published data only}

Green SS, Lamb GC, Schmitt S, Kaufman J. Oral versus repository corticosteroid therapy after hospitalization for the treatment of asthma. Journal of Allergy and Clinical Immunology 1995;95(1):15‐22. [PUBMED: 7822659 ]CENTRAL

Hofmann 2008 {published data only}

Hofmann M, Rodríguez JE, Klatt C. What is the best treatment for an adult whose asthma exacerbation has not completely responded to 5 days of oral corticosteroids?. Evidence‐Based Practice 2008;11(8):4. CENTRAL

Kelso 2014 {published data only}

Kelso JM. Question 1: prednisolone or dexamethasone for acute exacerbations of asthma: do they have similar efficacy in the management of exacerbations of childhood asthma?. Pediatrics 2014;134:S179. [DOI: 10.1542/peds.2014‐1817AAAA]CENTRAL

Ozpenpe 2011 {published data only}

Ozpenpe O, Aydogan M, Iraneci R. Comparison of the efficacy and side effects of intramuscular, intravenous and oral methylprednisolone used in the acute exacerbation of childhood asthma: A randomized clinical trial. Allergy 2011;66(S94):668. [DOI: 10.1111/j.1398‐9995.2011.02650.x]CENTRAL

Razi 2006 {published data only}

Razi E, Moosavi GA. A comparative efficacy of oral prednisone with intramuscular triamcinolone in acute exacerbation of asthma. Iran Journal of Allergy, Asthma and Immunology 2006;5(1):17‐22. [DOI: 05.01/ijaai.1722]CENTRAL

Watnick 2016 {published data only}

Watnick CS, Fabbri D, Arnold DH. Single‐dose oral dexamethasone is effective in preventing relapse after acute asthma exacerbations. Annals of Allergy, Asthma & Immunology 2016;116(2):171‐2. [DOI: 10.1016/j.anai.2015.11.015]CENTRAL

White 2010 {published data only}

White S. BET 2 Dexamethasone versus prednisolone in asthma. Emergency Medicine Journal 2010;27(9):716‐7. [DOI: 10.1136/emj.2010.101212]CENTRAL

Referencias de los estudios en espera de evaluación

Droszcz 1981 {published data only}

Droszcz W, Lech B, Piotrowska B, Garlicki A. Clinical evaluation of betamethasone depot. Pneumonologia Polska 1981;49(8‐9):645‐8. [PUBMED: 7029485]CENTRAL

Referencias adicionales

Alangari 2014

Alangari AA. Corticosteroids in the treatment of acute asthma. Annals of Thoracic Medicine 2014;9(4):187‐92. [10.4103/1817‐1737.140120]

Castro‐Rodriguez 2016

Castro‐Rodriguez JA, Beckhaus AA, Forno E. Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: systematic review with meta‐analysis. Pediatric Pulmonology 2016;51(8):868‐76. [DOI: 10.1002/ppul.23429]

CDC 2011

CDC. Asthma in the U.S. CDC Vital Signs. www.cdc.gov/vitalsigns/asthma.May 2011.

Croisant 2014

Croisant S. Epidemiology of asthma: prevalence and burden of disease. Advances in Experimental Medicine and Biology 2014;795:17‐29. [DOI: 10.1007/978‐1‐4614‐8603‐9_2]

Ducharme 1993

Ducharme FM, Kramer MS. Relapse following emergency treatment for acute asthma: can it be predicted or prevented?. Journal of Clinical Epidemiology 1993;46(12):1395‐402. [PUBMED: 8263566]

Ducharme 2011

Ducharme FM, Zemek RL, Chalut D, McGillivray D, Noya FJ, Resendes S, et al. Written action plan in pediatric emergency room improves asthma prescribing, adherence, and control. American Journal of Respiratory and Critical Care Medicine 2011;183(2):195‐203. [DOI: 10.1164/rccm.201001‐0115OC]

Emerman 1999

Emerman CL, Woodruff PG, Cydulka RK, Gibbs MA, Pollack CV, Camargo CA. Prospective multicenter study of relapse following treatment for acute asthma among adults presenting to the emergency department. MARC investigators. Multicenter Asthma Research Collaboration. Chest 1999;115(4):919‐27. [PUBMED: 10208187]

Emerman 2001

Emerman CL, Cydulka RK, Crain EF, Rowe BH, Radios MS, Camargo CA, et al. Prospective multicenter study of relapse after treatment for acute asthma among children presenting to the emergency department. Journal of Pediatrics 2001;138(3):318‐24. [DOI: 10.1067/mpd.2001.111320]

GINA 2017

Global Initiative for Asthma. Global Initative for Asthma. Global Strategy for Asthma Management and Prevention, 2017. ginasthma.org/2017‐gina‐report‐global‐strategy‐for‐asthma‐management‐and‐prevention/ (accessed 12 September 2016).

GRADEpro GDT [Computer program]

McMaster University (developed by EvidencePrime). GRADEpro GDT. Version accessed 24 November 2016. Hamilton (ON): McMaster University (developed by EvidencePrime), 2015.

Higgins 2011

Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Krishnan 2009

Krishnan JA, Davis SQ, Naureckas ET, Gibson P, Rowe BH. An umbrella review: corticosteroid therapy for adults with acute asthma. American Journal of Medicine 2009;122(11):977‐91. [DOI: 10.1016/j.amjmed.2009.02.013]

Moher 2009

Moher D, Liberati A, Tetzlaff J, Altman D. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Medicine 2009;6(7):e1000097. [DOI: 10.1371/journal.pmed.1000097]

Normansell 2016

Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/14651858.CD011801.pub2]

Paniagua 2017

Paniagua N, Lopez R, Muñoz N, Tames M, Mojica E, Arana‐Arri E, et al. Randomized trial of dexamethasone versus prednisone for children with acute asthma exacerbations. Journal of Pediatrics 2017;191:190‐6.e1. [DOI: doi.org/10.1016/j.jpeds.2017.08.030]

Review Manager 2014 [Computer program]

Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Rowe 1999

Rowe BH, Travers AH, Holroyd BR, Kelly KD, Bota GW. Nebulized ipratropium bromide in acute pediatric asthma: does it reduce hospital admissions among children presenting to the emergency department?. Annals of Emergency Medicine 1999;34(1):75‐85. [PUBMED: 10381998]

Rowe 2001

Rowe BH, Spooner C, Ducharme F, Bretzlaff J, Bota G. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database of Systematic Reviews 2001, Issue 1. [DOI: 10.1002/14651858.CD002178]

Rowe 2007a

Rowe BH, Spooner C, Ducharme F, Bretzlaff J, Bota G. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/14651858.CD000195.pub2]

Rowe 2007b

Rowe BH, Wong E, Blitz S, Diner B, Mackey D, Ross S, et al. Adding long‐acting beta‐agonists to inhaled corticosteroids after discharge from the emergency department for acute asthma: a randomized controlled trial. Academic Emergency Medicine 2007;14(10):833‐40. [DOI: 10.1197/j.aem.2007.06.020]

Rowe 2009

Rowe BH, Voaklander DC, Wang D, Senthilselvan A, Klassen TP, Marrie TJ, et al. Asthma presentations by adults to emergency departments in Alberta, Canada: a large population‐based study. Chest 2009;135(1):57‐65. [DOI: 10.1378/chest.07‐3041]

Rowe 2015

Rowe BH, Villa‐Roel C, Majumdar SR, Abu‐Laban RB, Aaron SD, Stiell IG, et al. Rates and correlates of relapse following ED discharge for acute asthma: a Canadian 20‐site prospective cohort study. Chest 2015;147(1):140‐9. [DOI: 10.1378/chest.14‐0843]

Rowe 2017

Rowe BH, Kirkland SW, Vandermeer B, Campbell S, Newton A, Ducharme FM, et al. Prioritizing systemic corticosteroid treatments to mitigate relapse in adults with acute asthma: A systematic review and network meta‐analysis. Academic Emergency Medicine 2017;24(3):371‐81. [DOI: 10.1111/acem.13107]

Topal 2014

Topal E, Gücenmez OA, Harmanci K, Arga M, Derinoz O, Turktas I. Potential predictors of relapse after treatment of asthma exacerbations in children. Annals of Allergy, Asthma and Immunology 2014;112(4):361‐4. [DOI: 10.1016/j.anai.2014.01.025]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Al‐Wahadneh 2006

Methods

A prospective, randomised, non‐blinded clinical trial

Comparison of IM dexamethasone to oral prednisolone

Randomisation and allocation concealment methods were reported but methods were not described

Participants

Patients with known history of asthma who presented to the ED with a moderate asthma exacerbation who did not require admission on presentation and had no evidence of varicella exposure or fever and did not take any systemic corticosteroids within 2 weeks of the start of the study

A locally modified scoring system based on GINA guidelines for the management of asthma was used to evaluate the clinical response at presentation, and 5 days after treatment.

Ages: enrolled patients 9 months to 14 years. Mean age of IM corticosteroid group: 79.7 months. Mean age of oral corticosteroid group: 45.4 months

Reported enrolling patients with mild‐moderate exacerbations. Unable to assess exacerbation severity based on baseline PEF

Set in Jordan

Sex: 20 men, 9 women

Interventions

  • Interventions: single IM dose of dexamethasone (1.7 mg/kg; mean steroid dosage: 24 mg) versus oral prednisolone (2 mg/kg/day; mean steroid dosage: 19.2 mg per day) for 5 days. No placebo was provided for either group

  • Co‐interventions in the ED: not reported

  • Co‐interventions at discharge: salbutamol (100 mcg/puff; 1 puff every 4 to 6 hours as needed)

Outcomes

  • Change in clinical asthma score from day 1 through day 5 of treatment.

  • Relapse (defined as unscheduled patient returns due to symptoms and signs requiring treatment with systemic corticosteroids after initial clearance within 21 days of treatment)

  • Clearing of an asthma exacerbation (defined as resolving of asthma symptoms and signs, the use of salbutamol less than 2 puffs per day and an additional course of systemic corticosteroids were not considered necessary)

Notes

Authors did not respond to requests for clarification.

No registered protocol was identified.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided on how patients were randomised.

Quote (p. 16): "Patients were randomised to receive either a single Intramuscular (IM) dose of dexamethasone acetate (1.7 mg/kg) or prednisolone taken orally each day for 5 days (2 mg/kg//day)."

Allocation concealment (selection bias)

Unclear risk

Study did not comment on allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Reported as a non‐blinded study.

Quote (p. 16): "The study is prospective randomised and non‐blinded."

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Reported as a non‐blinded study.

Quote (p. 16): "The study is prospective randomised and non‐blinded."

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient reporting of attrition/exclusions to permit a judgement.

Selective reporting (reporting bias)

Unclear risk

No protocol available.

Other bias

Unclear risk

Source of funding not provided. Baseline imbalance detected, dexamethasone group significantly older than prednisolone group.

Quote (p. 16): "Males out‐numbered females in both groups (13:4 in the dexamethasone group, and 7:5 in the second group). Patients in dexamethasone acetate group were older than those in prednisolone group (P = 0.007), which can risk of bias ably be explained by the small‐sized sample and the random assignment of patients to either group."

Chan 2001

Methods

A prospective, randomised, double‐blinded, controlled clinical trial

Comparison of IM betamethasone versus oral prednisone

Randomisation was reported but method was not described.

Allocation concealment: pharmacy provided randomised, sequentially numbered, sealed kits that contained an injection of betamethasone 2 mL and 7 placebo capsules, or an injection of saline 2 mL and 7 capsules of prednisone 50 mg each

Participants

Patients who presented to the ED with an exacerbation of asthma and had no contraindication to prednisone or betamethasone and were likely to be discharged after treatment.

The diagnosis of asthma was made clinically by the ED physician.

Patients who received oral or parenteral corticosteroids within 24 hours of enrolment were not excluded from study.

Ages: enrolled patients 18 years and above. Mean age of IM corticosteroid group: 31.6 years (SD: 13.1). Mean age of oral corticosteroids group: 21.1 years (SD: 10.7)

Exacerbation severity not discussed. Exacerbation severity estimated as mild/moderate based on baseline PEF

Set in Canada

Sex: 77 men, 94 women

Interventions

  • Interventions: single IM dose of betamethasone (12 mg) followed by 7 oral placebo capsules for 7 days versus oral prednisone (50 mg/day for 7 days), in addition to a single IM placebo injection

  • Co‐interventions in the ED: supplemental oxygen, nebulized salbutamol and in some cases, intravenous (IV) or oral systemic corticosteroids

  • Co‐interventions at discharge: not standardized. Recommendations for the use of current medications including beta₂‐agonists, ICS, and theophylline were left to the discretion of the attending physician.

Outcomes

  • Primary outcome: proportion of patients in each group who relapsed at 7 and 21 days (defined as an unscheduled visit to the ED, medical clinic or the patient’s own family physician for treatment of continuing or worsening symptoms of asthma)

  • Secondary end points: symptom score, peak flows and adverse effects (simplified asthma scoring system (1 to 10) was obtained at 7 and 21 days consisting of shortness of breath, cough, wheeze, activity limitation and sleep disturbance. The patients were asked to score their symptoms in addition to morning and evening peak flow readings.)

Notes

No registered protocol was identified; however study authors were contacted and provided the study protocol.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided on how patients were randomised.

Quote (p. 148): "The hospital pharmacy provided sequentially numbered, sealed kits that were randomised to contain either ...."

Allocation concealment (selection bias)

Low risk

Pharmacy‐controlled central allocation. Drug kits were sealed and sequentially numbered.

Quote (p. 148): "The hospital pharmacy provided sequentially numbered, sealed kits that were randomised to contain either an injection of betamethasone 2 mL and seven placebo capsules, or an injection of saline 2 mL and seven capsules containing prednisone 50 mg each."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double blinded study. Drug kits opened by nurse not involved in study patient. Medication names were obscured so neither staff or patients knew medication name.

Quote (p. 149): "After consent was obtained, a kit was opened by a nurse who was not involved with the study patient. This nurse drew up the 2 mL solution and placed a translucent sleeve over the syringe to obscure the medication but to allow the graduations to be seen. The primary nurse involved with the patient was given the covered syringe and capsules, and administered the intramuscular injection."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessment completed by study coordinator blinded to treatment allocation. All instances of suspected relapses reviewed by investigators before un‐blinding.

Quote (p. 149): "Patients were contacted by telephone on day 7 and 21 by a study coordinator blinded to the treatment allocation, and asked if they sought treatment for their asthma since the initial ED visit." "Before un‐blinding, all instances of suspected relapse were reviewed by two of the investigators."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Detailed information on study attrition provided in flow diagram provided (p. 149). Excluded patients balanced between groups.

Quote (p. 149‐50): "During the study, 176 patients with acute asthma agreed to participate in the trial. After random assignment, five patients were subsequently excluded: three patients required hospitalisation before ED discharge; one was discovered to be on chronic prednisone; and one refused the injection." "At day 7, three patients were lost to follow‐up ‐ two in the prednisone group and one in the betamethasone group. By day 21, 12 patients were lost to follow‐up ‐ four in the prednisone group and eight in the betamethasone group. At the completion of the study, follow‐up information was available for 159 patients (93%)."

Selective reporting (reporting bias)

Low risk

Protocol made available to authors by study investigators (protocol not registered). All pre‐selected outcomes reported.

Other bias

Low risk

Study appears to be free of other sources of bias. Source of funding stated.

Quote (p. 152): "Supported by a grant by Research and Development of the University of Calgary, Calgary, Alberta."

Gordon 2007

Methods

A prospective, randomised, non‐blinded controlled clinical trial

Comparison of a single dose of IM dexamethasone versus oral prednisolone

Randomization was reported but method was not described.

Allocation concealment method was accomplished using sequentially numbered opaque study packets containing group assignments.

Participants

Patients with known history of asthma who presented to the ED with moderate asthma exacerbation who did not require admission on presentation.

Asthma was defined as at least 2 prior episodes of respiratory illness treated with bronchodilators.

Clinical asthma score adapted from a previous pulmonary score was used to evaluate asthma children aged from 5 to 17 years measuring: respiratory rate, retractions and wheezing.

Reported enrolling patients with moderate exacerbations. Unable to assess exacerbation severity based on baseline PEF

Ages: enrolled patients 18 months to 7 years. Median age of IM corticosteroid group: 38 months (IQR: 29‐59). Median age of oral corticosteroid group: 42 months (IQR: 28‐60.5)

Patients who received IV therapy (not due to vomiting but to severity of asthma) were excluded from study.

Set in United States

Sex: 110 men, 71 women

Interventions

  • Interventions: single IM dose of dexamethasone (0.6 mg/kg to a maximum of 16 mg) versus oral prednisolone (2 mg/kg to a maximum of 50 mg once daily for 5 days). No placebo treatment was provided. A single dose of IV methylprednisolone (2 mg/kg) was given for patients who had repeated vomiting within 30 min after receiving oral prednisolone.

  • Co‐interventions in the ED: supplemental oxygen, albuterol, and ipratropium nebulization treatments

  • Co‐interventions at discharge: not standardized. The decision to provide patients with Inhaled beta₂‐agonists or ICS was left to the discretion of the attending physician. The use of additional systemic corticosteroids post‐discharge was allowed if prescribed by another physician.

Outcomes

  • Primary outcome: change in asthma score from the initial score on presentation to ED to the score assigned at day 4 of follow‐up visit

  • Secondary outcomes: hospital admission, respiratory signs, and need for unplanned medical visits during the 2 weeks after enrolment

Notes

Authors were not contacted

No registered protocol was identified

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided on how patients were randomised.

Quote (p. 521): "After written informed consent was obtained, we randomised patients to 1 of 2 treatment groups in blocks of 6, 8, or 10."

Allocation concealment (selection bias)

Low risk

Allocation concealment ensured via sequentially numbered opaque packets containing group assignments kept in ED and opened by physician immediately after enrolment.

Quote (p. 522): "Allocation concealment was maintained by use of sequentially numbered opaque study packets containing group assignments, which were kept in the ED and opened by the treating physician immediately after enrolment."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Non‐blinded study.

Quote (p. 522): "Treating physicians were not masked to study group." "At the time of disposition from the ED or 3 hours after enrolment for those patients still in the ED, physicians not blinded to group assignment performed a standardized repeat physical examination including the assessment of a second asthma score." Quote (p. 527): "The only people masked to group assignment in this study were the investigators who assigned follow‐up scores at the 4‐day return visit."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessment completed via physician blinded to group assignment and not involved in patient's care on the initial visit.

Quote (p. 523): "At the 4‐day follow‐up visit, a physician masked to group assignment and not involved in the patient's care on the initial visit performed a standard examination, including assignment of an asthma score. Physicians and guardians were instructed not to engage in any conversation before completion of the physical examination. After completing and recording this physical examination, the physician administered a structured interview regarding interim use of bronchodilators and ICS, guardian's perception of bronchodilators and ICS, guardian's perception of clinical improvement, need for further medical care since enrolment, and compliance with oral steroid regimen."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Detailed information on study attrition provided in flow diagram provided (p. 523). Excluded patients balanced between groups.

Quote (p. 523, 525‐6): "Of 194 randomised patients, 13 were subsequently excluded from the study (7 in the dexamethasone arm and 6 in the prednisolone arm) for the following reasons: 6 had initial asthma scores of only 2, 4 had previously participated, 1 had only one prior episode of wheezing, 1 had taken prednisolone within the previous month, and 1 patient was randomised to the dexamethasone group, but inappropriately given prednisolone in the ED. The guardians of 2 included patients randomised to dexamethasone withdrew their consent for further participation during the ED visit (one before drug administration, one afterward)."

Selective reporting (reporting bias)

Unclear risk

No available protocol

Other bias

Unclear risk

Source of funding was not stated.

Gries 2000

Methods

A prospective, randomised, non‐blinded controlled clinical trial with blinded outcome assessors

Comparison of single dose of IM dexamethasone versus oral prednisolone

Randomization and allocation concealment were reported but methods were not discussed.

Participants

Patients with known history of asthma who presented to the ED with mild to moderate asthma exacerbation who did not require admission on presentation

Asthma was defined as recurrent coughing, wheezing, or shortness of breath responsive to corticosteroids or β₂‐agonists.

Asthma exacerbation was defined as increased asthma signs and symptoms unresponsive to the patient’s routine asthma medications and additional β₂‐agonist therapy.

Clinical asthma score was defined as a composite score of wheeze and cough scores ranging from 0 to 8.

Reported to enrolling patients with mild‐moderate exacerbations. Unable to assess exacerbation severity based on baseline PEF

Ages: enrolled patients 6 months to 7 years. Mean age of IM corticosteroid group: 38 months (SD: 18). Mean age of oral corticosteroid group: 36 months (SD: 22)

Patients were excluded from study if they received IV corticosteroids on the ED initial visit.

Set in United States

Sex: 23 men, 9 women

Interventions

  • Interventions: single IM dose of dexamethasone (˜ 1.7 mg/kg) versus oral prednisolone (˜ 2 mg/kg/day for 5 days, twice daily). No placebo treatment was provided.

  • Co‐interventions in the ED: albuterol nebulization treatments. The use of systemic corticosteroids prior to enrolment were permitted (reported but not discussed).

  • Co‐interventions at discharge: albuterol (2 mg/ml suspension, 100 µg/puff by meted‐dose inhaler, or 5% nebulizer solution) every 4 to 6 hours as needed

Outcomes

  • Primary outcomes: change in asthma signs or symptoms (clinical asthma score) from days 1 through 5 of treatment, number of patients whose clinical status returned to baseline by day 5, albuterol use, and tolerance of the corticosteroid medication

  • Follow up days 3, 5, 7, 14, and 28

  • Relapse defined as within 14 days of resolution of the initial asthma exacerbation; the patient had another exacerbation requiring treatment with corticosteroids

Notes

Authors were not contacted.

No registered protocol was identified.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided on how patients were randomised.

Quote (p. 299): "Once enrolled in the study, patients were randomised to receive either a single IM dose of dexamethasone acetate (Dalalone, Forest Pharmaceuticals, 16 mg/mL) or prednisone (either suspension 3 mg/mL or tablets—patient’s choice) taken orally each day for 5 days."

Allocation concealment (selection bias)

Unclear risk

No information on allocation concealment provided.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Non‐blinded study.

Quote (p. 300‐1): "The study investigators were blinded to the patient’s treatment arm. Patients and parents were not blinded. The nurses in the paediatric clinic who administered the IM injections did not discuss the patients with the study investigators." "Investigator blinding was achieved in all but 4 patients. For 2 of these children, the nurses told an investigator that they had administered a shot, and the other 2 children disclosed what they had received (one IM Dex and one oral Pred). A second investigator, who was still blinded, completed the assessments."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessors were blinded to group assignment.

Quote (p. 300): "The study investigators were blinded to the patient’s treatment arm"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Study attrition provided. Excluded patients balanced between groups.

Quote: (p. 300): "From September 1996 through February 1997, we approached 35 children (age range, 8 months to 7 years) and their legal guardians concerning enrolment, and all but 2 agreed to participate in the study. Sixteen children received IM Dex, and 17 were randomised to receive oral Pred. One child, a 16‐month‐old (randomised to IM Dex), was withdrawn on her second study day for treatment of a persistent cough by an emergency department physician who noted no wheezing or respiratory distress but gave her an additional IM injection of dexamethasone."

Selective reporting (reporting bias)

Unclear risk

No protocol available.

Other bias

Unclear risk

No source of funding provided.

Hoffman 1988

Methods

A prospective, randomised, double‐blinded controlled clinical trial

Comparison of IM methylprednisolone versus oral methylprednisolone

Randomization and allocation concealment were reported but methods were not described.

Participants

Patients who presented to the ED with an acute asthma and were discharged after ED treatment

Inclusion criteria required eligible patients to fulfil the American Thoracic Society for the diagnosis of asthma.

Ages: enrolled patients 15 to 55 years. Mean age of IM corticosteroid group: 42 years (SEM: 4). Mean age of oral corticosteroid group: 37 years (SEM:4)

Exacerbation severity not discussed. Exacerbation severity estimated as severe based on baseline PEF

Patients who received corticosteroids at the time of presentation were excluded from study.

Patients who needed admission or remained in ED for more than 6 hours were excluded from study.

Set in United States

Sex: 11 men, 7 women

Interventions

  • Interventions: single IM injection of methylprednisolone sodium acetate (80 mg) followed by 7 days of oral placebo therapy versus oral methylprednisolone (64 mg days 1 and 2, 32 mg day 3, 24 mg day 4, 16 mg day 5, 12 mg day 6, and 4 mg day 7), in addition to a IM placebo injection

  • Co‐interventions in the ED: inhaled metaproterenol, subcutaneous epinephrine (0.3 mL) at 20 min intervals (up to 3 doses), IV aminophylline (5.6 mg/kg over 20 min) followed by a maintenance drip between 0.3 and 0.7 mg/kg/hr, nasal oxygen at 2 L/min to 3 L/min, and all patients received IV methylprednisolone sodium succinate 4 mg/kg (before enrolment into the study)

  • Co‐interventions at discharge: oral anhydrous long‐acting theophylline at a dose of 300 mg twice a day, inhaled beta₂‐agonists as needed

  • The use of additional systemic and ICS other than what was provided to patients at discharge were not permitted.

Outcomes

Follow‐up between days 5 and 7

  • Symptoms (wheeze or cough)

  • Drug compliance

  • Adverse reactions

  • Fischl index

  • Relapse (defined as a need for further emergency care within 10 days of entry into the study)

  • PEF measurements reported and discussed

Notes

Authors did not respond to requests for clarification.

No registered protocol was identified.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided on how patients were randomised.

Quote (p. 11): "All subjects were given an IV injection of 4 mg/kg of methylprednisolone sodium succinate, then randomised in double‐blind fashion to receive either an IM injection of methylprednisolone sodium acetate..."

Allocation concealment (selection bias)

Unclear risk

No information on allocation concealment provided.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Double‐blind study. Oral placebo and oral methylprednisolone was indistinguishable from each other but unsure if IM placebo and IM methylprednisolone was indistinguishable.

Quote (p. 11): "All subjects were given an IV injection of 4 mg/kg of methylprednisolone sodium succinate, then randomised in double‐blind fashion to receive either an IM injection of methylprednisolone sodium acetate..." "Oral placebo and oral methylprednisolone were indistinguishable, and the dosage and tapering schedule were the same as in our previous study."

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information on blinding of outcome assessment

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Missing patients balanced between groups.

Quote (p. 12): "Follow‐up was obtained by return visit in seven of eight patients in group 1, and in nine of ten patients in group 2."

Selective reporting (reporting bias)

Unclear risk

No protocol available

Other bias

Unclear risk

No source of funding provided

Klig 1997

Methods

A prospective, randomised, non‐blinded clinical trial with blinded outcome assessors

Comparison of IM dexamethasone versus oral prednisone

Randomization was stated but method was not described.

Allocation concealment was accomplished using sealed opaque packets.

Participants

Patients, who had 2 prior episodes of wheezing and were treated with beta‐2‐adrenergic agents, presented to ED with mild to moderate wheezing and did not require admission to hospital

Enrolment of patients was based on the pulmonary index (0 to 3), assessment of a clinical score for asthma, and pulse oximetry on arrival to ED.

Ages: enrolled patients 3 to 16 years. Mean age of IM corticosteroid group: 82 months (SD: 46). Mean age of oral corticosteroid group: 63 months (SD: 36)

Reported enrolling patients with mild‐moderate exacerbations. Unable to assess exacerbation severity based on baseline PEF

Patients were excluded from study if they received corticosteroids within the last month or were hospitalised for asthma treatment within the last 2 months prior to the study.

Set in United States

Sex: 24 men, 18 women

Interventions

  • Interventions: single IM dose of dexamethasone (0.3 mg/kg, maximum of 15 mg) versus oral prednisone (2 mg/kg/day, maximum of 100 mg) for 3 days. No placebo treatment was provided.

  • Co‐interventions in the ED: nebulized albuterol (5 mg/mL solution) 0.5 mL in 2 mL of normal saline by oxygen face mask set at 6 L of flow every 20 to 30 min

  • Co‐interventions at discharge: albuterol (liquid, nebulized, or metered dose inhaler (MDI) 4 times a day until follow‐up was completed

  • Additional systemic corticosteroids were not permitted.

Outcomes

Followed up on day 5 either by assessment in out‐patient clinic or via telephone interview

  • Primary outcome: symptomatic improvement on follow‐up 5 days after initial treatment and relapse and/or clinical deterioration within 5 days after discharge from ED (relapse was defined as the worsening of respiratory symptoms after discharge from ED, visits to the out‐patient clinic or emergency department, or admission to the hospital)

  • Secondary outcome: pulmonary index scores on discharge from ED, and further corticosteroid use after the follow‐up evaluation

Notes

Author was contacted and provided clarification on allocation concealment and source of funding

No registered protocol was identified

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided on how patients were randomised. Study authors confirmed via personal communication that randomisation was in blocks.

Quote (p. 421): "Patients were randomly assigned by sealed packets to receive either oral prednisone tablets 2 mg/kg or IM dexamethasone 0.3 mg/kg."

Personal communication: "Randomization was in blocks."

Allocation concealment (selection bias)

Low risk

Allocation concealment ensured via sealed packets. Study authors confirmed via personal communication that the sealed packets were opaque.

Quote (p. 421): "Patients were randomly assigned by sealed packets to receive either oral prednisone tablets 2 mg/kg or IM dexamethasone 0.3 mg/kg."

Personal communication: "Sealed packets were opaque"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Non‐blinded study.

Quote (p. 421): "The assigned corticosteroid was administered in an unblinded manner immediately after enrolment in the study."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessors blinded. Stated that Investigators (Physicians) were blinded to patient's treatment.

Quote (p. 422): "Patient follow‐up was conducted on the fifth day after discharge from the PED by a physician blinded to group assignment."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Patient exclusions balanced between groups.

Quote (p. 422): "Forty‐four patients participated in the pilot study of whom 23 received a single dose of IM dexamethasone and 21 received 3 days of oral prednisone. Two patients from the IM dexamethasone group were admitted to the hospital shortly after enrolment and therefore were removed from the study. The remaining 42 patients were discharged to home, resulting in an even distribution between the IM dexamethasone and oral prednisone groups."

Selective reporting (reporting bias)

Unclear risk

No protocol available.

Other bias

Low risk

The study appears to be free of other sources of bias. Study authors confirmed via personnel communication that the study was not funded.

Personal communication: "Study was funded via supplies only (decadron from Merck Pharmaceuticals)."

Lahn 2004

Methods

A prospective, randomised, double blinded, placebo‐controlled clinical trial

Comparison of single dose of IM methylprednisolone versus oral methylprednisolone

Randomisation was accomplished using computer‐generated random set of numbers (20 blocks).

Allocation concealment was maintained by research pharmacist using computer generated set of numbers to package medications in balanced blocks (20). Intramuscular injection (methylprednisolone and placebo) with similar appearances and covered content were prepared and administered by a nurse who was not involved in the study. Oral methylprednisolone and placebo were identical in appearance and were given in identical containers.

Participants

Patients diagnosed with asthma (based on the American Thoracic Society Guidelines (1962), PEF ≤ 70% predicted during the ED visit with a minimum PEF ≥ 40% predicted, and included both clinical symptoms and physical examination findings), who presented with an asthma exacerbation and were expected to be discharged after the ED treatment

Exacerbation severity not discussed. Exacerbation severity estimated as mild/moderate based on baseline PEF

Ages: enrolled patients 18 to 45 years. Mean age of IM corticosteroid group: 33 years (SD: 8). Mean age of oral corticosteroid group: 33 years (SD: 8)

Patients who received systemic corticosteroids (within 1 month prior to the study), theophylline or inhaled anticholinergic agents were excluded from study.

Set in United States

Sex: 56 men, 131 women

Interventions

  • Interventions: single IM dose of methylprednisolone (160 mg) followed by 8‐day supply of tapering oral placebo versus oral methylprednisolone (8‐day tapering dose: day 1, 32 mg; day 2, 32 mg; day 3, 24 mg; day 4, 24 mg; day 5, 16 mg; day 6, 16 mg; day 7, 8 mg; day 8, 8 mg) in addition to a IM placebo injection

  • Co‐interventions in the ED: nebulized beta₂‐agonist agents and IV injection of 1 mg/kg methylprednisolone

  • Co‐interventions at discharge: albuterol MDI

  • Patients were permitted to use ICS post‐discharge if patients had been using them previously

  • Patients were instructed to continue all other medications without further clarification

Outcomes

  • Primary end point: relapse within 10 days of discharge (defined as the need to seek unscheduled care at the doctor’s office, a clinic, or ED for symptoms of persistent or worsening asthma, determined by phone contact)

  • Secondary end point: relapse between 11 and 21 days

  • Self‐reported pain of IM injection and the development of bruising, swelling, or continued pain for more than 7 days at the site of injection were reported and discussed

  • Intention‐to‐treat and sensitivity analysis were reported and discussed

Notes

Authors were contacted, but were unable to provide protocol

No registered protocol was identified

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation completed via block randomised computer generated numbers.

Quote (p. 363): "The medication was prepared and block‐randomised by a research pharmacist who used a computer‐generated set of random numbers to package the medications in balanced blocks of 20 (i.e., each block of 20 medication packets contained 10 packets of oral methylprednisolone plus an IM placebo and 10 packets of IM methylprednisolone plus oral placebo."

Allocation concealment (selection bias)

Low risk

Pharmacy‐controlled central allocation.

Quote (p. 363): "The randomisation code was held by the pharmacist and was not broken during the course of the study." "To the best of our knowledge, allocation concealment was maintained."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double blinded study. Corticosteroids administered to patients via a study nurse not involved with the patient. Intramuscular injection was administered in a private setting with no one else present. Nurse instructed not to provide patients or staff information on contents of the syringe. Nurse covered the syringe so that other staff or patients could not see what was in the syringe. Oral placebo and corticosteroids was identical in appearance.

Quote (p. 363): "The injection was reconstituted and administered by an ED nurse who was not blinded to the treatment but who had no involvement in any aspect of the study. This individual was instructed not to provide the patient, physician, or study personnel with any information about the contents of the syringe. Although the placebo and methylprednisolone injections were similar in appearance, the nurse also was instructed not to allow anyone to see the contents of the syringe. The injection was administered in a private setting with no one else present. The oral methylprednisolone and oral placebo were identical in appearance and were given to patients in identical containers. To the best of our knowledge, allocation concealment was maintained."

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided on blinding of outcome assessment.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Detailed information on study attrition provided in flow diagram provided (p. 364). Excluded patients balanced between groups.

Quote (p. 364): "One hundred ninety patients were entered into the study over a 60‐month period from November 1997 to November 2002. As shown in the diagram of the Consolidated Standards of Reporting trials, three patients (all in the oral methylprednisolone/IM placebo group) were removed after study entry due to protocol violations. One patient’s asthma was too severe to be discharged safely from the ED, a second patient did not receive a ‐agonist prescription at ED discharge, and a third patient was instructed by the primary physician to discontinue the study medication at day 5. Seven patients (IM administration group, three patients; oral administration group, four patients) were lost to follow‐up and were excluded from the primary efficacy analysis. The remaining 180 patients, 92 of whom received IM methylprednisolone plus oral placebo, and 88 of whom received oral methylprednisolone plus IM placebo, completed the protocol and were available for follow‐up at 10 days. All patients reached for follow‐up at 10 days were successfully contacted again for follow‐up at 21 days. No patients who were lost to follow‐up at 10 days were available for follow‐up at 21 days."

Selective reporting (reporting bias)

Unclear risk

No protocol available.

Other bias

Low risk

Study funded by pharmaceutical company. Authors state that pharmaceutical company just provided financial support, and was not involved in the design, execution, data analysis, or manuscript preparation. Quote (p. 362): "This research was funded in part by an unrestricted grant from Pharmacia & Upjohn (currently, Pfizer), who, other than providing financial support, were not involved in any way with the design, execution, data analysis, or manuscript preparation."

Lee 1993

Methods

A prospective, randomised, double blinded, placebo‐controlled clinical trial

Comparison of single dose of IM dexamethasone versus oral dexamethasone

Randomization was accomplished using computer‐generated random set of numbers (9 blocks).

Allocation concealment was reported but method was not described.

Participants

Patients diagnosed with asthma (based on the American Thoracic Society criteria, 1962), presented to ED with acute asthma and did not require hospital admission

Exacerbation severity not discussed. Exacerbation severity estimated as mild/moderate based on baseline PEF

Ages: enrolled patients 16 to 60 years. Mean age of IM corticosteroid group: 37 years (SD: 4). Mean age of oral corticosteroid group: 40 years (SD: 4)

Patients who received systemic corticosteroids prior to enrolment in the study were excluded.

Set in Taiwan

Sex: 20 men, 16 women

Interventions

Patients were divided into 3 groups (A, B, and C)

  • Group A received single IM placebo versus oral placebo treatment for 7 days.

  • Group B received single IM dexamethasone (10 mg) versus oral placebo treatment for 7 days.

  • Group C received single IM placebo versus oral dexamethasone 1.5 mg twice a day for 7 days.

Tapering of dexamethasone was as follows: 3.0 mg day 1 and 2, 2.0 mg day 3, 1.5 mg day 4, 1.0 mg day 5, 0.75 mg day 6 and 0.5 mg day 7)

  • Co‐interventions in the ED: oxygen, IV aminophylline, and fenoterol inhalation

  • Co‐interventions at discharge: oral anhydrous long‐acting theophylline 250 mg twice daily, beta₂‐agonist inhaler as needed

  • The use of ICS and supplemental corticosteroids were not permitted

Outcomes

Primary and secondary outcomes were not defined.

  • Relapse (defined as a need for another ED visit) within 7 days and between 11 and 21 days

  • Symptoms (coughing, wheezing) and the number of daily beta₂‐agonist inhaler use

  • PEF and FEV1/FVC (%)

Notes

Attempts to contact the authors failed

No registered protocol was identified

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Patients randomised via block randomised computer generated numbers.

Quote (p. 26): "The subjects were randomly assigned into one of three groups using a double blind model. Randomisation was by means of a set of computer‐generated set of random‐numbers in blocks of nine."

Allocation concealment (selection bias)

Unclear risk

No information on allocation concealment provided.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Double‐blinded study. Oral corticosteroids and oral placebo were indistinguishable from each other but no information provided as to whether IM corticosteroids were indistinguishable from IM placebo.

Quote (p. 26): "The subjects were randomly assigned into one of three groups using a double blind model." "The oral dexamethasone and oral placebo were indistinguishable."

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided on outcome assessment blinding.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Study did not report attrition/exclusions.

Selective reporting (reporting bias)

Unclear risk

No protocol available.

Other bias

Unclear risk

Source of funded not provided.

Schuckman 1998

Methods

A prospective, randomised, double‐blinded, placebo‐controlled clinical trial

Comparison of IM triamcinolone versus oral prednisone

Randomization was accomplished using computer‐generated random numbers.

Allocation concealment was reported and discussed as pharmacy controlled by using computerized generated set of numbers to package medications and placebo into sequentially numbered kits.

Participants

Patients presented to the ED with an asthma exacerbation that had an initial PEF < 350 L/min and did not require admission to hospital on ED presentation

The diagnosis of asthma was according to the American Thoracic Society criteria (1987)

Patients were excluded from study if had received corticosteroids within 2 weeks prior to ED presentation or were unable or unwilling to attend follow‐up evaluation.

Ages: Enrolled patients 18 to 50 years. Mean age of IM corticosteroid group: 31 years (SD: 9). Mean age of oral corticosteroid group: 32 years (SD: 9)

Exacerbation severity not reported. Exacerbation severity estimated as mild/moderate based on baseline PEF

Set in United States

Sex: 47 mean, 107 women

Interventions

  • Interventions: single IM dose of triamcinolone (40 mg) followed by 10 placebo tablets twice daily for 5 days versus oral prednisone (20 mg twice daily) for 5 days, in addition to a single IM placebo injection. Placebo was provided for both groups

  • Co‐interventions in the ED: albuterol, oral or IV corticosteroids

  • Co‐interventions at discharge: beta‐2‐agonist MDI at least 4 times daily, albuterol MDI, regular medications including those for asthma including ICS, cromolyn sodium, ipratropium bromide MDI, and oral antibiotics

Outcomes

Patients were followed up 7 to 10 days after ED enrolment.

  • Primary outcome: relapse (defined as an unscheduled or emergency visit to a physician’s office to the ED for persistent or worsening symptoms of asthma within 7 days of the initial ED visit)

  • Secondary outcome: difference in symptom severity on the fifth day post‐discharge

  • Compliance (defined as having an empty pill bottles at the follow‐up visit)

  • PEF

Notes

Author was contacted and provided clarification on the methodology of blinding and outcome data. Was unable to provide copy of the study protocol.

No registered protocol was identified.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation completed via computer generated set of random numbers.

Quote (p. 334): "A computer‐generated set of random numbers was used by the hospital pharmacy to package the active medications and placebos into sequentially numbered kits."

Allocation concealment (selection bias)

Low risk

Pharmacy controlled allocation concealment. Medications and placebos packaged in sequentially numbered kits.

Quote (p. 334): "A computer‐generated set of random numbers was used by the hospital pharmacy to package the active medications and placebos into sequentially numbered kits."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded study. Study authors confirmed via personnel communication that the study medications were indistinguishable from each other.

Personal communication: "Syringes were prefilled and tablets looked similar for placebo and prednisone. Each patient received injection and pill bottle. They brought their bottle to follow‐up."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessors (physicians) were blinded to the patient's group assignment.

Quote (p. 335): "Physicians evaluating patients at follow‐up remained blinded to drug group assignment."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Detailed information on study attrition provided in flow diagram provided (p. 337). Excluded patients balanced between groups.

Quote (p. 335‐6): "We approached 186 patients who were potentially eligible; 15 (9%) refused to participate, and 3 (2%) resided out of town and could not return for follow‐up. A total of 168 patients were enrolled, 82 in the triamcinolone group and 86 in the prednisone group. Fourteen patients were withdrawn from analysis: 6 (3 in each group) for protocol violations because the patient was older than 50 years of age, and 8 (1 in the triamcinolone group and 7 in the prednisone group) because they were lost to follow‐up. The final study population was 154 patients, 78 in the triamcinolone group and 76 in the prednisone group."

Selective reporting (reporting bias)

Unclear risk

No protocol available.

Other bias

Low risk

No other potential source of bias found. Source of funding provided.

Quote (p. 333): "Research supported by the Summa Health System Foundation."

Abbreviations

ED: emergency department

FEV1: forced expiratory volume

FVC: forced vital capacity

ICS: inhaled corticosteroids

IM: intramuscular

MDI: metered dose inhaler

PEF: peak expiratory flow

IV: intravenous

SD: standard deviation

SEM: standard error of mean

IQR: interquartile range

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Andrews 2012

Did not compare IM versus oral corticosteroids

Droszcz 1985

Not an RCT/CCT

Ducharme 2004

Not an RCT/CCT

Green 1995

Did not provide a single dose of intramuscular corticosteroids

Hofmann 2008

Did not compare IM versus oral corticosteroids

Kelso 2014

Not an RCT/CCT

Ozpenpe 2011

Patients not discharged from ED

Razi 2006

Did not provide a single dose of intramuscular corticosteroids

Watnick 2016

Not an RCT/CCT

White 2010

Not an RCT/CCT

Characteristics of studies awaiting assessment [ordered by study ID]

Droszcz 1981

Methods

No abstract for full publication available. Unable to assess

Participants

No abstract for full publication available. Unable to assess

Interventions

No abstract for full publication available. Unable to assess

Outcomes

No abstract for full publication available. Unable to assess

Notes

No abstract for full publication available. Unable to make assessment on study eligibility

Data and analyses

Open in table viewer
Comparison 1. Intramuscular versus oral corticosteroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Relapse Show forest plot

9

804

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.24]

Analysis 1.1

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 1 Relapse.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 1 Relapse.

2 Relapse intention to treat Show forest plot

9

821

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.72, 1.26]

Analysis 1.2

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 2 Relapse intention to treat.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 2 Relapse intention to treat.

3 Subgroup analysis: children versus adults Show forest plot

9

804

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.24]

Analysis 1.3

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 3 Subgroup analysis: children versus adults.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 3 Subgroup analysis: children versus adults.

3.1 Children

4

245

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.48, 1.53]

3.2 Adults

5

559

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.71, 1.33]

4 Subgroup analysis: relapse within 10 days and over 10 days post‐discharge Show forest plot

9

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 1.4

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 4 Subgroup analysis: relapse within 10 days and over 10 days post‐discharge.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 4 Subgroup analysis: relapse within 10 days and over 10 days post‐discharge.

4.1 Within 10 days post‐discharge

7

742

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.51, 1.07]

4.2 Greater than 10 days post‐discharge

5

556

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.74, 1.33]

5 Subgroup analysis: mild/moderate versus severe exacerbations Show forest plot

5

557

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.70, 1.32]

Analysis 1.5

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 5 Subgroup analysis: mild/moderate versus severe exacerbations.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 5 Subgroup analysis: mild/moderate versus severe exacerbations.

5.1 Mild/moderate exacerbations

4

539

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.71, 1.34]

5.2 Severe exacerbations

1

18

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.01, 4.47]

6 Sensitivity analysis: risk of bias Show forest plot

5

559

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.71, 1.33]

Analysis 1.6

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 6 Sensitivity analysis: risk of bias.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 6 Sensitivity analysis: risk of bias.

7 Sensitivity analysis: oral corticosteroid prescriptions greater than 5 days Show forest plot

8

762

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.24]

Analysis 1.7

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 7 Sensitivity analysis: oral corticosteroid prescriptions greater than 5 days.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 7 Sensitivity analysis: oral corticosteroid prescriptions greater than 5 days.

8 Sensitivity analysis: fixed effects Show forest plot

9

804

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.69, 1.19]

Analysis 1.8

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 8 Sensitivity analysis: fixed effects.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 8 Sensitivity analysis: fixed effects.

9 Sensitivity analysis: corticosteroids in ED Show forest plot

5

320

Risk Ratio (M‐H, Random, 95% CI)

0.76 [0.45, 1.29]

Analysis 1.9

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 9 Sensitivity analysis: corticosteroids in ED.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 9 Sensitivity analysis: corticosteroids in ED.

10 Serious adverse events; hospitalization following discharge Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.10

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 10 Serious adverse events; hospitalization following discharge.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 10 Serious adverse events; hospitalization following discharge.

11 Adverse events Show forest plot

5

404

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.64, 1.07]

Analysis 1.11

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 11 Adverse events.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 11 Adverse events.

12 Adverse events: nausea/vomiting/GI distress Show forest plot

3

320

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.09, 3.59]

Analysis 1.12

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 12 Adverse events: nausea/vomiting/GI distress.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 12 Adverse events: nausea/vomiting/GI distress.

13 Adverse events: insomnia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.13

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 13 Adverse events: insomnia.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 13 Adverse events: insomnia.

14 Adverse events: personality changes Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.14

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 14 Adverse events: personality changes.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 14 Adverse events: personality changes.

15 Adverse events: pain Show forest plot

2

181

Risk Ratio (M‐H, Random, 95% CI)

1.75 [0.32, 9.66]

Analysis 1.15

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 15 Adverse events: pain.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 15 Adverse events: pain.

16 Adverse events: swelling Show forest plot

2

180

Risk Ratio (M‐H, Random, 95% CI)

4.76 [0.57, 39.84]

Analysis 1.16

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 16 Adverse events: swelling.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 16 Adverse events: swelling.

17 Adverse events: redness Show forest plot

2

175

Risk Ratio (M‐H, Random, 95% CI)

13.5 [0.77, 235.63]

Analysis 1.17

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 17 Adverse events: redness.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 17 Adverse events: redness.

18 Pulmonary function: peak expiratory flow (L/min) Show forest plot

4

272

Mean Difference (IV, Random, 95% CI)

‐7.78 [‐38.83, 23.28]

Analysis 1.18

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 18 Pulmonary function: peak expiratory flow (L/min).

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 18 Pulmonary function: peak expiratory flow (L/min).

19 Pulmonary function: FEV₁/FVC (%) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.19

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 19 Pulmonary function: FEV₁/FVC (%).

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 19 Pulmonary function: FEV₁/FVC (%).

20 Symptom persistence Show forest plot

3

80

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.14, 1.20]

Analysis 1.20

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 20 Symptom persistence.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 20 Symptom persistence.

21 Symptom persistence: cough Show forest plot

3

178

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.17, 2.73]

Analysis 1.21

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 21 Symptom persistence: cough.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 21 Symptom persistence: cough.

22 Symptom persistence: wheezing Show forest plot

3

177

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.14, 2.52]

Analysis 1.22

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 22 Symptom persistence: wheezing.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 22 Symptom persistence: wheezing.

23 24‐hour beta agonist use Show forest plot

2

48

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.21, 1.37]

Analysis 1.23

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 23 24‐hour beta agonist use.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 23 24‐hour beta agonist use.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

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

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 1 Relapse.
Figures and Tables -
Analysis 1.1

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 1 Relapse.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 2 Relapse intention to treat.
Figures and Tables -
Analysis 1.2

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 2 Relapse intention to treat.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 3 Subgroup analysis: children versus adults.
Figures and Tables -
Analysis 1.3

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 3 Subgroup analysis: children versus adults.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 4 Subgroup analysis: relapse within 10 days and over 10 days post‐discharge.
Figures and Tables -
Analysis 1.4

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 4 Subgroup analysis: relapse within 10 days and over 10 days post‐discharge.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 5 Subgroup analysis: mild/moderate versus severe exacerbations.
Figures and Tables -
Analysis 1.5

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 5 Subgroup analysis: mild/moderate versus severe exacerbations.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 6 Sensitivity analysis: risk of bias.
Figures and Tables -
Analysis 1.6

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 6 Sensitivity analysis: risk of bias.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 7 Sensitivity analysis: oral corticosteroid prescriptions greater than 5 days.
Figures and Tables -
Analysis 1.7

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 7 Sensitivity analysis: oral corticosteroid prescriptions greater than 5 days.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 8 Sensitivity analysis: fixed effects.
Figures and Tables -
Analysis 1.8

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 8 Sensitivity analysis: fixed effects.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 9 Sensitivity analysis: corticosteroids in ED.
Figures and Tables -
Analysis 1.9

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 9 Sensitivity analysis: corticosteroids in ED.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 10 Serious adverse events; hospitalization following discharge.
Figures and Tables -
Analysis 1.10

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 10 Serious adverse events; hospitalization following discharge.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 11 Adverse events.
Figures and Tables -
Analysis 1.11

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 11 Adverse events.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 12 Adverse events: nausea/vomiting/GI distress.
Figures and Tables -
Analysis 1.12

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 12 Adverse events: nausea/vomiting/GI distress.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 13 Adverse events: insomnia.
Figures and Tables -
Analysis 1.13

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 13 Adverse events: insomnia.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 14 Adverse events: personality changes.
Figures and Tables -
Analysis 1.14

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 14 Adverse events: personality changes.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 15 Adverse events: pain.
Figures and Tables -
Analysis 1.15

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 15 Adverse events: pain.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 16 Adverse events: swelling.
Figures and Tables -
Analysis 1.16

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 16 Adverse events: swelling.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 17 Adverse events: redness.
Figures and Tables -
Analysis 1.17

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 17 Adverse events: redness.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 18 Pulmonary function: peak expiratory flow (L/min).
Figures and Tables -
Analysis 1.18

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 18 Pulmonary function: peak expiratory flow (L/min).

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 19 Pulmonary function: FEV₁/FVC (%).
Figures and Tables -
Analysis 1.19

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 19 Pulmonary function: FEV₁/FVC (%).

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 20 Symptom persistence.
Figures and Tables -
Analysis 1.20

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 20 Symptom persistence.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 21 Symptom persistence: cough.
Figures and Tables -
Analysis 1.21

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 21 Symptom persistence: cough.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 22 Symptom persistence: wheezing.
Figures and Tables -
Analysis 1.22

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 22 Symptom persistence: wheezing.

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 23 24‐hour beta agonist use.
Figures and Tables -
Analysis 1.23

Comparison 1 Intramuscular versus oral corticosteroids, Outcome 23 24‐hour beta agonist use.

Summary of findings for the main comparison. Intramuscular corticosteroids compared to Oral corticosteroids for acute asthma

Intramuscular corticosteroids compared to Oral corticosteroids for acute asthma

Patient or population: patients with acute asthma
Settings: Acute care settings
Intervention: Intramuscular corticosteroids
Comparison: Oral corticosteroids

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Oral corticosteroids

Intramuscular corticosteroids

Relapse

201 per 1000

12 fewer per 1000
(from 56 fewer to 48 more)

RR 0.94
(0.72 to 1.24)

804
(9 studies)

⊕⊕⊝⊝
low1,2

Relapse within 10 days postdischarge

154 per 1000

40 fewer per 1000

(from 75 fewer to 11 more)

RR 0.74
(0.51 to 1.07)

742
(7 studies)

⊕⊕⊕⊝
moderate1

Relapse occurring after 10 days postdischarge

245 per 1000

2 fewer per 1000
(from 64 fewer to 81 more)

RR 0.99
(0.74 to 1.33)

556
(5 studies)

⊕⊕⊝⊝
low1,2

Adverse events

294 per 1000

50 fewer per 1000
(from 106 fewer to 21 more)

RR 0.83
(0.64 to 1.07)

404
(5 studies)

⊕⊕⊝⊝
low1,3

Pulmonary function: Peak expiratory flow

The mean pulmonary function: peak expiratory flow ranged across control groups from
304 to 419 litres/min

The mean pulmonary function: peak expiratory flow in the intervention groups was
7.78 liters/min lower
(38.83 lower to 23.28 higher)

272
(4 studies)

⊕⊕⊕⊝
moderate2

Symptom persistence

537 per 1000

317 fewer per 1000
(from 461 fewer to 107 more)

RR 0.41
(0.14 to 1.2)

80
(3 studies)

⊕⊕⊝⊝
low1,3

24hour beta agonist use

375 per 1000

172 fewer per 1000
(from 296 fewer to 139 more)

RR 0.54
(0.21 to 1.37)

48
(2 studies)

⊕⊕⊝⊝
low1,3

*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% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk 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.

1 Downgraded 1 level for risk of bias. Majority of studies received an unclear risk of bias for random sequence generation and selective outcome reporting
2 Downgraded 1 level for imprecision including wide confidence intervals (including both benefit, harm, and no effect)
3 Downgraded 1 level for Imprecision including wide confidence intervals (including both benefit, harm, and no effect) and few events

Figures and Tables -
Summary of findings for the main comparison. Intramuscular corticosteroids compared to Oral corticosteroids for acute asthma
Table 1. Exacerbation severity

Studies

Pulmonary function: Eligibility criteria

Exacerbation severity

Al‐Wahadneh 2006

Severity estimated using modified scoring system based on GINA guidelines. Reported to enrolling patients with mild‐moderate exacerbations, however baseline pulmonary function of the groups was not reported.

Unable to assess

Chan 2001

Reported mean baseline PEF greater than 200 L/min: IM group: 270 L/min (SD: 103); oral group: 261 L/min (SD: 104).

Mild/moderate

Gordon 2007

Reported to enrolling patients identified as moderate exacerbations, however baseline pulmonary function was not reported.

Unable to assess

Gries 2000

Applied adapted exacerbation severity score (unspecified). Reported to enrolling patients rated as mild/moderate, however baseline pulmonary function of the groups was not reported.

Unable to assess

Hoffman 1988

Reported baseline mean PEF of enrolled patients of less than 150 L/min: IM group: 129 L/min (SD:14); oral group: 141 L/min (SD: 14).

Severe

Klig 1997

Exacerbation severity estimated via pulmonary index score. Study reported to enrolling patients with mild/moderate exacerbations, however baseline pulmonary function was not reported.

Unable to assess

Lahn 2004

Eligibility criteria required patients to have a PEFR of ≤ 70% predicted with a minimum PEFR of ≥ 40%. Reported PEF of enrolled patients was ≥ 200 L/min: IM group: 205 L/min (SD: 70); oral group: 209 L/min (SD: 72).

Mild/moderate

Lee 1993

Reported mean baseline PEF of ≥ 200 L/min: IM group: 210 L/min (SD: 30); oral group: 208 L/min (SD: 26).

Mild/moderate

Schuckman 1998

Reported mean baseline PEF of ≥ 200 L/min: IM group: 243.6 L/min (SD: 64); oral group: 244.7 L/min (SD: 83).

Mild/moderate

Abbreviations:

GINA = Global Initiative for Asthma; PEF = Peak expiratory flow; PEFR = Peak expiratory flow rate; IM = intramuscular; SD = standard deviation

Figures and Tables -
Table 1. Exacerbation severity
Table 2. Study characteristics of included studies

Studies

Location/setting

Co‐interventions

Corticosteroid doses and durations

Methyprednisolone equivalency

Relapse outcome

Al‐Wahadneh 2006

Jordan, ED

Provided in ED: not stated

Provided at discharge: SABA

Dexamethasone (IM)

1.7 mg/kg

Mean dose: 24 mg

Single dose

Prednisolone (oral)

2 mg/kg/day for 5 days

Mean dose: 19.2 mg per day

Total dose: 96 mg

IM

Methylprednisone equivalency: 120 mg

Duration: intermediate half‐life (12 to 36 hours)

Oral

Methylprednisone equivalency:

76.8 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

1/16

Day 21

Oral group

3/14

Day 21

Chan 2001

Canada, ED

Provided in ED: SABA, methylxanthines, supplemental oral/IV corticosteroids

Provided at discharge: Methylxanthines, unspecified inhaled beta₂‐agonists, and ICS

Betamethasone (IM)

12 mg

Single dose. Received placebo capsules over 7 days.

Prednisone (oral)

50 mg a day for 7 days. Received a single placebo injection

Total dose: 350 mg

IM

Methylprednisone equivalency:

72 mg

Duration: intermediate half‐life (12 to 36 hours)

Oral

Methylprednisone equivalency:

280 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

12/86

Day 7

Oral group

19/82

Day 7

Gordon 2007

United States, Pediatric ED

Provided in ED: SABA, ipratropium bromide. IV corticosteroids for patients who vomited oral corticosteroids.

Provided at discharge: Inhaled beta₂‐agonists and ICS

Dexamethasone (IM)

0.6 mg/kg (max 16 mg)

Single dose

Prednisolone (oral)

2 mg/kg (max 50 mg) daily for 5 days

Total: 250 mg

IM

Methylprednisone equivalency:

80 mg

Duration: intermediate half‐life (12‐36 hours)

Oral

Methylprednisone equivalency:

200 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

8/69

Day 4

Oral group

11/73

Day 4

IM group

15/68

Day 14

Oral group

16/73

Day 14

Gries 2000

United States, Tertiary medical center

Provided in ED: SABA

Provided at discharge: SABA

Dexamethasone (IM)

Patients 6 to 12 months old received 16 mg.

Patients 13 to 35 months old received 24 mg.

Children ≥ 36 months received 36 mg.

Single dose

Prednisone (oral)

2 mg/kg a day for 5 days

Total dose: unclear

IM

Methylprednisone equivalency:

Unable to assess

Oral

Methylprednisone equivalency:

Unable to assess

IM group

1/15

Day 28

Oral group

3/17

Day 28

Hoffman 1988

United States, ED

Provided in ED: SABA, epinephrine, methylxanthines, IV corticosteroids

Provided at discharge: Methylxanthine and inhaled beta₂‐agonists

Methylprednisonlone (IM)

80 mg

Single dose. Received placebo capsules for 7 days

Methylprednisolone (oral)

Tapering dose over 7 days.

Total dose: 216 mg

Received placebo injection

IM

Methylprednisone equivalency:

80 mg

Duration: intermediate half‐life (12 to 36 hours)

Oral

Methylprednisone equivalency:

216 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

0/8 day

Day 7

Oral group

2/10

Day 7

Klig 1997

United States, Pediatric ED

Provided in ED: SABA

Provided at discharge: SABA

Dexamethasone (IM)

0.3 mg/kg

Total dose: 15 mg

Single dose

Prednisone (oral)

2 mg/kg a day for 3 days

Total dose: 100 mg

IM

Methylprednisone equivalency:

75 mg

Duration: intermediate half‐life (12 to 36 hours)

Oral

Methylprednisone equivalency:

80 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

0/21

Day 5

Oral group

0/21

Day 5

Lahn 2004

United States, ED

Provided in ED: inhaled beta₂‐agonists, IV corticosteroids

Provided at discharge: SABA

Methylprednisolone (IM)

160 mg

Single dose. Received placebo capsules for 8 days

Methylprednisolone (oral)

Tapering dose over 8 days.

Total dose: 160 mg (tapering dose 32 mg day 1).

Received placebo injection

IM

Methylprednisone equivalency:

80 mg

Duration: intermediate half‐life (12 to 36 hours)

Oral

Methylprednisone equivalency:

80 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

13/92

Day 10

Oral group

12/88

Day 10

IM group

17/92

Day 21

Oral group

20/88

Day 21

Lee 1993

Taiwan, ED

Provided in ED: SABA, methylxanthines

Provided at discharge: Methylxanthine and inhaled beta₂‐agonists

Dexamethasone (IM)

10 mg

Single dose. Received placebo capsules for 7 days

Dexamethasone (oral)

Tapering dose over 7 days.

11.75 mg total. Received placebo injection

IM

Methylprednisone equivalency:

50 mg

Duration: intermediate half‐life (12 to 36 hours)

Oral

Methylprednisone equivalency:

58.8 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

1/17

Day 7

Oral group

0/19

Day 7

Schuckman 1998

United States, ED

Provided in ED: SABA, oral/IV corticosteroids

Provided at discharge: SABA, antibiotics, ICS, cromolyn sodium, ipratropium bromide

Triamcinolone (IM)

40 mg

Single dose. Received placebo capsules for 5 days

Prednisone (oral)

40 mg a day for 5 days.

Total dose: 160 mg

Received placebo injection

IM

Methylprednisone equivalency:

40 mg

Duration: intermediate half‐life (12 to 36 hours)

Oral

Methylprednisone equivalency:

160 mg

Duration: intermediate half‐life (12 to 36 hours)

IM group

7/78

Day 7

Oral group

11/76

Day 7

ED = emergency department; SABA = short‐acting beta₂‐agonists; LABA = long‐acting beta₂‐agonists; IV = intravenous; IM = intramuscular; ICS = inhaled corticosteroids

Figures and Tables -
Table 2. Study characteristics of included studies
Comparison 1. Intramuscular versus oral corticosteroids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Relapse Show forest plot

9

804

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.24]

2 Relapse intention to treat Show forest plot

9

821

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.72, 1.26]

3 Subgroup analysis: children versus adults Show forest plot

9

804

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.24]

3.1 Children

4

245

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.48, 1.53]

3.2 Adults

5

559

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.71, 1.33]

4 Subgroup analysis: relapse within 10 days and over 10 days post‐discharge Show forest plot

9

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Within 10 days post‐discharge

7

742

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.51, 1.07]

4.2 Greater than 10 days post‐discharge

5

556

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.74, 1.33]

5 Subgroup analysis: mild/moderate versus severe exacerbations Show forest plot

5

557

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.70, 1.32]

5.1 Mild/moderate exacerbations

4

539

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.71, 1.34]

5.2 Severe exacerbations

1

18

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.01, 4.47]

6 Sensitivity analysis: risk of bias Show forest plot

5

559

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.71, 1.33]

7 Sensitivity analysis: oral corticosteroid prescriptions greater than 5 days Show forest plot

8

762

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.24]

8 Sensitivity analysis: fixed effects Show forest plot

9

804

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.69, 1.19]

9 Sensitivity analysis: corticosteroids in ED Show forest plot

5

320

Risk Ratio (M‐H, Random, 95% CI)

0.76 [0.45, 1.29]

10 Serious adverse events; hospitalization following discharge Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

11 Adverse events Show forest plot

5

404

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.64, 1.07]

12 Adverse events: nausea/vomiting/GI distress Show forest plot

3

320

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.09, 3.59]

13 Adverse events: insomnia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

14 Adverse events: personality changes Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

15 Adverse events: pain Show forest plot

2

181

Risk Ratio (M‐H, Random, 95% CI)

1.75 [0.32, 9.66]

16 Adverse events: swelling Show forest plot

2

180

Risk Ratio (M‐H, Random, 95% CI)

4.76 [0.57, 39.84]

17 Adverse events: redness Show forest plot

2

175

Risk Ratio (M‐H, Random, 95% CI)

13.5 [0.77, 235.63]

18 Pulmonary function: peak expiratory flow (L/min) Show forest plot

4

272

Mean Difference (IV, Random, 95% CI)

‐7.78 [‐38.83, 23.28]

19 Pulmonary function: FEV₁/FVC (%) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

20 Symptom persistence Show forest plot

3

80

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.14, 1.20]

21 Symptom persistence: cough Show forest plot

3

178

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.17, 2.73]

22 Symptom persistence: wheezing Show forest plot

3

177

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.14, 2.52]

23 24‐hour beta agonist use Show forest plot

2

48

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.21, 1.37]

Figures and Tables -
Comparison 1. Intramuscular versus oral corticosteroids