- Email: [email protected]
Corticosteroid treatment for acute croup
EVIDENCE-BASED EMERGENCY MEDICINE/SYSTEMATIC REVIEW ABSTRACT
EBEM Commentator Brian H. Rowe, MD, MSc From the Division of Emergency Medicine, University of Alberta, Edmonton, Alberta, Canada.
Corticosteroid Treatment for Acute Croup [Ann Emerg Med. 2002;40:353-355.]
S Y S T E M AT I C R E V I E W SOURCE
This is a systematic review abstract, a regular feature of the Annals’ Evidence-Based Emergency Medicine (EBEM) series. Each features an abstract of a systematic review from the Cochrane Database of Systematic Reviews and a commentary by an emergency physician knowledgeable in the subject area. The source for this systematic review abstract is: Ausejo M, Saenz A, Pham B, Kellner JD, Johnson DW, Moher D, Klassen TP. Glucocorticoids for croup (Cochrane Review). In: The Cochrane Library. Issue 3. Oxford, United Kingdom: Update Software; 2001. The Annals’ EBEM editors prepared the abstract of this Cochrane systematic review as well as the Evidence-Based Medicine Teaching Points. Copyright © 2002 by the American College of Emergency Physicians. 0196-0644/2002/$35.00 + 0 47/3/127085 doi:10.1067/mem.2002.127085
SEPTEMBER 2002
40:3
OBJECTIVE
To determine the effect of corticosteroids in the treatment of children with croup.
ANNALS OF EMERGENCY MEDICINE
D ATA S O U R C E S
The Controlled Trials Register of the Cochrane Library was searched; it includes studies identified by the Acute Respiratory Infection Review Group through the hand searching of key journals. In addition, studies were identified by searching MEDLINE, Excerpta Medica, and EMBASE (to August 1997). Reviewers wrote to study authors to inquire about published and unpublished articles. The review is considered updated to June 1999. STUDY SELECTION
Studies were included if they were randomized controlled trials using any glucocorticoid therapy in the treatment of acute croup in children. Independent review of the trials was completed by 2 reviewers for possible relevance and then again for inclusion. D ATA E X T R A C T I O N
One reviewer extracted data, and 2 reviewers independently assessed trial quality. Authors were contacted for missing data. Risk difference (RD), effect size (ES), and number needed to treat (NNT) with 95% confidence intervals (CIs) are reported.
3 5 3
EBEM/SYSTEMATIC REVIEW ABSTRACT
M A I N R E S U LT S
Comunidad de Madrid
Twenty-four studies involving 2,221 patients were included in this updated review; 10 trials involved outpatients. Corticosteroid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of –1.0 (95% CI –1.5 to –0.6) and at 12 hours of –1.0 (95% CI –1.6 to –0.4); at 24 hours, this improvement was no longer significant (–1.0; 95% CI –2.0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with corticosteroids: a decrease of 9% (95% CI 2% to 16%) among those treated with budesonide and of 12% (95% CI 4% to 20%) among those treated with dexamethasone. There was also a significant decrease in the number of hours spent in the emergency setting (–11 hours; 95% CI –18 to 4), and inpatient hospital stay was reduced by 16 hours (95% CI –31 to 1 hour). Finally, patients discharged from the emergency department after corticosteroid treatment were less likely to relapse (0.46; 95% CI 0.35 to 0.61). Publication bias appears to play an important role in the interpretation of these results.
c/o Donnell 50
CONCLUSIONS
Both dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer cointerventions are used and the length of time spent in the hospital is decreased in children treated with glucocorticoids. Cochrane Systematic Review Author Contact M. Ausejo, MD Head, Pharmaceutical’s Expenditure Evaluation Service Consejuria de Sanidad
3 5 4
Madrid, Spain E-mail [email protected]
C O M M E N TA R Y: C L I N I C A L I M P L I C AT I O N
Acute presentations of viral croup account for a significant proportion of ED visits in children younger than 10 years of age. The vast majority (>90%) of these patients are discharged after ED care, and a small proportion of these patients experience a return visit within the next week.1,2 Overall, a very small percentage (<1%) require interventions to control the airway. Nonetheless, impairments in sleep and quality of life for parents and children have stimulated considerable interest in possible treatments for this disease. Epinephrine and racemic epinephrine have both been used for the treatment of severe croup, and moist humidified air has been advocated without much evidence. In the late 1980s, a systematic review identified the benefit of systemic corticosteroids for the treatment of hospitalized children with croup.3 This evidence was sufficient to be endorsed as a standard of care in some countries.4 Despite this, there remains debate regarding which patients benefit from corticosteroid treatment and whether this treatment should be administered to patients with a relatively benign disease. This systematic review searched for the best available evidence regarding the use of corticosteroids in the treatment of croup. Their analysis demonstrated that corticosteroids work rather quickly (within 6 hours) when administered early in the ED management of croup by improving croup severity scores. These findings are similar to the treatment of asthma, where benefit
has been observed with the use of both systemic5 and inhaled6 corticosteroids within 6 hours of presentation to the ED. The primary analysis also demonstrated a reduction in admissions and length of stay for corticosteroid-treated patients; this benefit was clearly of clinical importance and not offset by any increase in side effects attributed to the medications. Although the use of mist tents and intubation complications were not changed by corticosteroid administration, the numbers in these subgroups were small. Most importantly, discharged patients were far less likely to return to the ED for a relapse in the subsequent 48 hours. Overall, the review provides strong support for the use of corticosteroids in croup. The review failed to demonstrate a clear superiority of one agent over others. However, the ease of administration of oral dexamethasone compared with the delivery of nebulized or intramuscular agents makes its choice an easy one; dexamethasone is also the cheapest agent in this setting. Fortunately, the effectiveness of both other delivery routes provides the clinician with the option of using nebulized or intramuscular agents in the face of complicated croup requiring admission or resulting in vomiting. What is not answered from this review is whether children with very mild croup benefit from corticosteroid therapy; further research in this setting is currently under way. TA K E H O M E M E S S A G E
Treatment of croup with corticosteroids is an effective therapy for children seen in the ED with croup. Both systemic (oral, intramuscular) corticosteroids (eg, predominantly dexamethasone) and inhaled budesonide are effective agents. Because
ANNALS OF EMERGENCY MEDICINE
40:3
SEPTEMBER 2002
EBEM/SYSTEMATIC REVIEW ABSTRACT
of their cost, the use of inhaled corticosteroids should be reserved for select patients (patients who cannot tolerate dexamethasone or oral intake).
is rounded to 8, and the 95% CI is often also reported. The result represents the number of patients who would need to receive active treatment to prevent one adverse outcome.
EBEM Commentator Contact Brian H. Rowe, MD, MSc
REFERENCES
Division of Emergency Medicine
1. Kaditis AG, Wald ER. Viral croup: current diagnosis and treatment. Pediatr Infect Dis J. 1998;17:827834.
University of Alberta 1G1.63 WMC, 8440-112 Street Edmonton, Alberta T6G 2B7 Canada E-mail [email protected]
EVIDENCE-BASED MEDICINE TEACHING POINTS Updates of Cochrane reviews. Coch-
rane reviews are regularly updated when new research information becomes available. This may be in the form of trials that were inadvertently missed in the original search or production of new research data. This feature of Cochrane reviews represents a major methodologic advantage compared with paperbased reviews, which are “old” at the time of publication. This feature permits reviews to be revised to reflect changes in the literature and is particularly important in emerging therapies. NNT. Many methods are used to express the overall therapeutic benefit/harm in randomized trials and systematic reviews, including odds ratios (ORs), relative risks (RRs), P values, 95% CIs, and absolute and relative risk reduction. Debates rage regarding their strengths and weaknesses, which further confuse clinicians and readers of research. One alternative is to report the NNT, which is the inverse of the difference between the control event rate (CER) and the treatment event rate (TER). In a study in which the CER equals 25% (0.25) and the TER equals 12% (0.12), the NNT is 1/0.13 or 7.6. This number
SEPTEMBER 2002
40:3
2. Marx A, Torok TJ, Holman RC, et al. Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics. J Infect Dis. 1997;176:1423-1427. 3. Kairys SW, Olmstead EM, O’Connor GT. Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials. Pediatrics. 1989;83:683-693. 4. Steroid therapy for croup in children admitted to hospital. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. Can Med Assoc J. 1992;147:429-432. 5. Rowe BH, Spooner C, Ducharme FM, et al. Early emergency department treatment of acute asthma with systemic corticosteroids (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford, United Kingdom: Update Software; 2002. 6. Edmonds ML, Camargo CA Jr, Pollack CV Jr, et al. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford, United Kingdom: Update Software; 2002.
ANNALS OF EMERGENCY MEDICINE
3 5 5
EBEM Commentator Brian H. Rowe, MD, MSc From the Division of Emergency Medicine, University of Alberta, Edmonton, Alberta, Canada.
Corticosteroid Treatment for Acute Croup [Ann Emerg Med. 2002;40:353-355.]
S Y S T E M AT I C R E V I E W SOURCE
This is a systematic review abstract, a regular feature of the Annals’ Evidence-Based Emergency Medicine (EBEM) series. Each features an abstract of a systematic review from the Cochrane Database of Systematic Reviews and a commentary by an emergency physician knowledgeable in the subject area. The source for this systematic review abstract is: Ausejo M, Saenz A, Pham B, Kellner JD, Johnson DW, Moher D, Klassen TP. Glucocorticoids for croup (Cochrane Review). In: The Cochrane Library. Issue 3. Oxford, United Kingdom: Update Software; 2001. The Annals’ EBEM editors prepared the abstract of this Cochrane systematic review as well as the Evidence-Based Medicine Teaching Points. Copyright © 2002 by the American College of Emergency Physicians. 0196-0644/2002/$35.00 + 0 47/3/127085 doi:10.1067/mem.2002.127085
SEPTEMBER 2002
40:3
OBJECTIVE
To determine the effect of corticosteroids in the treatment of children with croup.
ANNALS OF EMERGENCY MEDICINE
D ATA S O U R C E S
The Controlled Trials Register of the Cochrane Library was searched; it includes studies identified by the Acute Respiratory Infection Review Group through the hand searching of key journals. In addition, studies were identified by searching MEDLINE, Excerpta Medica, and EMBASE (to August 1997). Reviewers wrote to study authors to inquire about published and unpublished articles. The review is considered updated to June 1999. STUDY SELECTION
Studies were included if they were randomized controlled trials using any glucocorticoid therapy in the treatment of acute croup in children. Independent review of the trials was completed by 2 reviewers for possible relevance and then again for inclusion. D ATA E X T R A C T I O N
One reviewer extracted data, and 2 reviewers independently assessed trial quality. Authors were contacted for missing data. Risk difference (RD), effect size (ES), and number needed to treat (NNT) with 95% confidence intervals (CIs) are reported.
3 5 3
EBEM/SYSTEMATIC REVIEW ABSTRACT
M A I N R E S U LT S
Comunidad de Madrid
Twenty-four studies involving 2,221 patients were included in this updated review; 10 trials involved outpatients. Corticosteroid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of –1.0 (95% CI –1.5 to –0.6) and at 12 hours of –1.0 (95% CI –1.6 to –0.4); at 24 hours, this improvement was no longer significant (–1.0; 95% CI –2.0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with corticosteroids: a decrease of 9% (95% CI 2% to 16%) among those treated with budesonide and of 12% (95% CI 4% to 20%) among those treated with dexamethasone. There was also a significant decrease in the number of hours spent in the emergency setting (–11 hours; 95% CI –18 to 4), and inpatient hospital stay was reduced by 16 hours (95% CI –31 to 1 hour). Finally, patients discharged from the emergency department after corticosteroid treatment were less likely to relapse (0.46; 95% CI 0.35 to 0.61). Publication bias appears to play an important role in the interpretation of these results.
c/o Donnell 50
CONCLUSIONS
Both dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer cointerventions are used and the length of time spent in the hospital is decreased in children treated with glucocorticoids. Cochrane Systematic Review Author Contact M. Ausejo, MD Head, Pharmaceutical’s Expenditure Evaluation Service Consejuria de Sanidad
3 5 4
Madrid, Spain E-mail [email protected]
C O M M E N TA R Y: C L I N I C A L I M P L I C AT I O N
Acute presentations of viral croup account for a significant proportion of ED visits in children younger than 10 years of age. The vast majority (>90%) of these patients are discharged after ED care, and a small proportion of these patients experience a return visit within the next week.1,2 Overall, a very small percentage (<1%) require interventions to control the airway. Nonetheless, impairments in sleep and quality of life for parents and children have stimulated considerable interest in possible treatments for this disease. Epinephrine and racemic epinephrine have both been used for the treatment of severe croup, and moist humidified air has been advocated without much evidence. In the late 1980s, a systematic review identified the benefit of systemic corticosteroids for the treatment of hospitalized children with croup.3 This evidence was sufficient to be endorsed as a standard of care in some countries.4 Despite this, there remains debate regarding which patients benefit from corticosteroid treatment and whether this treatment should be administered to patients with a relatively benign disease. This systematic review searched for the best available evidence regarding the use of corticosteroids in the treatment of croup. Their analysis demonstrated that corticosteroids work rather quickly (within 6 hours) when administered early in the ED management of croup by improving croup severity scores. These findings are similar to the treatment of asthma, where benefit
has been observed with the use of both systemic5 and inhaled6 corticosteroids within 6 hours of presentation to the ED. The primary analysis also demonstrated a reduction in admissions and length of stay for corticosteroid-treated patients; this benefit was clearly of clinical importance and not offset by any increase in side effects attributed to the medications. Although the use of mist tents and intubation complications were not changed by corticosteroid administration, the numbers in these subgroups were small. Most importantly, discharged patients were far less likely to return to the ED for a relapse in the subsequent 48 hours. Overall, the review provides strong support for the use of corticosteroids in croup. The review failed to demonstrate a clear superiority of one agent over others. However, the ease of administration of oral dexamethasone compared with the delivery of nebulized or intramuscular agents makes its choice an easy one; dexamethasone is also the cheapest agent in this setting. Fortunately, the effectiveness of both other delivery routes provides the clinician with the option of using nebulized or intramuscular agents in the face of complicated croup requiring admission or resulting in vomiting. What is not answered from this review is whether children with very mild croup benefit from corticosteroid therapy; further research in this setting is currently under way. TA K E H O M E M E S S A G E
Treatment of croup with corticosteroids is an effective therapy for children seen in the ED with croup. Both systemic (oral, intramuscular) corticosteroids (eg, predominantly dexamethasone) and inhaled budesonide are effective agents. Because
ANNALS OF EMERGENCY MEDICINE
40:3
SEPTEMBER 2002
EBEM/SYSTEMATIC REVIEW ABSTRACT
of their cost, the use of inhaled corticosteroids should be reserved for select patients (patients who cannot tolerate dexamethasone or oral intake).
is rounded to 8, and the 95% CI is often also reported. The result represents the number of patients who would need to receive active treatment to prevent one adverse outcome.
EBEM Commentator Contact Brian H. Rowe, MD, MSc
REFERENCES
Division of Emergency Medicine
1. Kaditis AG, Wald ER. Viral croup: current diagnosis and treatment. Pediatr Infect Dis J. 1998;17:827834.
University of Alberta 1G1.63 WMC, 8440-112 Street Edmonton, Alberta T6G 2B7 Canada E-mail [email protected]
EVIDENCE-BASED MEDICINE TEACHING POINTS Updates of Cochrane reviews. Coch-
rane reviews are regularly updated when new research information becomes available. This may be in the form of trials that were inadvertently missed in the original search or production of new research data. This feature of Cochrane reviews represents a major methodologic advantage compared with paperbased reviews, which are “old” at the time of publication. This feature permits reviews to be revised to reflect changes in the literature and is particularly important in emerging therapies. NNT. Many methods are used to express the overall therapeutic benefit/harm in randomized trials and systematic reviews, including odds ratios (ORs), relative risks (RRs), P values, 95% CIs, and absolute and relative risk reduction. Debates rage regarding their strengths and weaknesses, which further confuse clinicians and readers of research. One alternative is to report the NNT, which is the inverse of the difference between the control event rate (CER) and the treatment event rate (TER). In a study in which the CER equals 25% (0.25) and the TER equals 12% (0.12), the NNT is 1/0.13 or 7.6. This number
SEPTEMBER 2002
40:3
2. Marx A, Torok TJ, Holman RC, et al. Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics. J Infect Dis. 1997;176:1423-1427. 3. Kairys SW, Olmstead EM, O’Connor GT. Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials. Pediatrics. 1989;83:683-693. 4. Steroid therapy for croup in children admitted to hospital. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. Can Med Assoc J. 1992;147:429-432. 5. Rowe BH, Spooner C, Ducharme FM, et al. Early emergency department treatment of acute asthma with systemic corticosteroids (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford, United Kingdom: Update Software; 2002. 6. Edmonds ML, Camargo CA Jr, Pollack CV Jr, et al. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford, United Kingdom: Update Software; 2002.
ANNALS OF EMERGENCY MEDICINE
3 5 5