Online link: https://scihubtw.tw/10.1016/j.jpeds.2015.06.038

Multicenter retrospective cohort study

Objectives: To study the comparative effectiveness of dexamethasone vs prednisone/prednisolone in children hospitalized with asthma exacerbation not requiring intensive care.

Study design: This multicenter retrospective cohort study, using the Pediatric Health Information System, included children aged 4-17 years who were hospitalized with a principal diagnosis of asthma between January 1, 2007 and December 31, 2012. Children with chronic complex condition and/or initial intensive care unit (ICU) management were excluded. Propensity score matching was used to detect differences in length of stay (LOS), readmissions, ICU transfer, and cost between groups.

Results: 40 257 hospitalizations met inclusion criteria; 1166 (2.9%) received only dexamethasone. In the matched cohort (N = 1284 representing 34 hospitals), the LOS was significantly shorter in the dexamethasone group compared with the prednisone/prednisolone group. The proportion of subjects with a LOS of 3 days or more was 6.7% in the dexamethasone group and 12% in the prednisone/prednisolone group (P = .002). Differences in all-cause readmission at 7- and 30 days were not statistically significant. The dexamethasone group had lower costs of index admission ($2621 vs $2838; P < .001) and total episode of care (including readmissions) ($2624 vs $2856; P < .001) compared with the prednisone/prednisolone group. There were no clinically significant differences in ICU transfer or readmissions between groups.

Conclusions: Dexamethasone may be considered an alternative to prednisone/prednisolone for children hospitalized with asthma exacerbation not requiring admission to intensive care. (J Pediatr 2015;167:639-44).

Online link: https://scihubtw.tw/10.1016/j.jpeds.2017.08.030

Randomized Control Trial

Objective To determine whether 2 doses of dexamethasone is as effective as 5 days of prednisolone/ prednisone therapy in improving symptoms and quality of life of children with asthma exacerbations admitted to the emergency department (ED).

Study design: We conducted a randomized, noninferiority trial including patients aged 1-14 years who presented to the ED with acute asthma to compare the efficacy of 2 doses of dexamethasone (0.6 mg/kg/dose, experimental treatment) vs a 5-day course of prednisolone/prednisone (1.5 mg/kg/d, followed by 1 mg/kg/d on days 2-5, conventional treatment). Two follow-up telephone interviews were completed at 7 and 15 days. The primary outcome measures were the percentage of patients with asthma symptoms and quality of life at day 7. Secondary outcomes were unscheduled returns, admissions, adherence, and vomiting.

Results: During the study period, 710 children who met the inclusion criteria were invited to participate and 590 agreed. Primary outcome data were available in 557 patients. At day 7, experimental and conventional groups did not show differences related to persistence of symptoms (56.6%, 95% CI 50.6-62.6 vs 58.3%, 95% CI 52.3-64.2, respectively), quality of life score (80.0 vs 77.7, not significant [ns]), admission rate (23.9% vs 21.7%, ns), unscheduled ED return visits (4.6% vs 3.3%, ns), and vomiting (2.1% vs 4.4%, ns). Adherence was greater in the dexamethasone group (99.3% vs 96.0%, P < .05).

Conclusion: Two doses of dexamethasone may be an effective alternative to a 5-day course of prednisone/prednisolone for asthma exacerbations, as measured by persistence of symptoms and quality of life at day 7. (JPediatr 2017;191:190-6).

Online link: https://scihubtw.tw/10.1542/peds.2013-2273

Meta-analysis

Background and objective: Dexamethasone has been proposed as an equivalent therapy to prednisone/prednisolone for acute asthma exacerbations in pediatric patients. Although multiple small trials exist, clear consensus data are lacking. This systematic review and meta-analysis aimed to determine whether intramuscular or oral dexamethasone is equivalent or superior to a 5-day course of oral prednisone or prednisolone. The primary outcome of interest was return visits or hospital readmissions.

Methods: A search of PubMed (Medline) through October 19, 2013, by using the keywords dexamethasone or decadron and asthma or status asthmaticus identified potential studies. Six randomized controlled trials in the emergency department of children ≤18 years of age comparing dexamethasone with prednisone/prednisolone for the treatment of acute asthma exacerbations were included. Data were abstracted by 4 authors and verified by a second author. Two reviewers evaluated study quality independently and interrater agreement was assessed.

Results: There was no difference in relative risk (RR) of relapse between the 2 groups at any time point (5 days RR 0.90, 95% confidence interval [CI] 0.46-1.78, Q = 1.86, df = 3, I2 = 0.0%, 10-14 days RR 1.14, 95% CI 0.77-1.67, Q = 0.84, df = 2, I2 = 0.0%, or 30 days RR 1.20, 95% CI 0.03-56.93). Patients who received dexamethasone were less likely to experience vomiting in either the emergency department (RR 0.29, 95% CI 0.12-0.69, Q = 3.78, df = 3, I2 = 20.7%) or at home (RR 0.32, 95% CI 0.14-0.74, Q = 2.09, df = 2, I2 = 4.2%).

Conclusions: Practitioners should consider single or 2-dose regimens of dexamethasone as a viable alternative to a 5-day course of prednisone/prednisolone.

Online link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923200/

Systematic Review/ Meta-Analysis

Methods: A computerized literature search of PubMed, Embase, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases was carried out till 1st August 2019. Six Randomized controlled trials (RCTs) and 1 quasi-RCT were included. Dosage of dexamethasone and prednisone varied across studies. Studies were grouped based on the follow-up period and duration of dexamethasone administration.

Results: There was no significant difference in the relapse rate between dexamethasone and prednisone at 1–5 days (RR 1.46, 95%CI 0.69–3.7, P = 0.32; I² = 0%) and 10–15 days of follow up (RR 1.16, 95%CI 0.80–1.68, P = 0.44; I² = 0%). Pooled analysis found no significant difference in relapse rates with 1-day (RR 1.15, 95%CI 0.68–1.95, P = 0.60; I² = 0%) and 2-day dosage of dexamethasone (RR 1.25, 95%CI 0.82–1.92, P = 0.30; I² = 0%) compared to prednisone. Hospital readmission rates after initial discharge were not significantly different between the two drugs (RR 1.49, 95%CI 0.56–4.01, P = 0.43; I² = 0%). Frequency of vomiting at ED (RR 0.21, 95%CI 0.05–0.96, P = 0.04; I² = 50%) and at home (RR 0.42, 95%CI 0.25–0.69, P = 0.0007; I² = 0%) was significantly higher with prednisone as compared to dexamethasone.

Conclusion: While our results indicate that both dexamethasone and prednisone have similar relapse rates when used for acute asthmatic exacerbations, strong conclusions cannot be drawn due to paucity of large scale RCTs and limited quality of evidence. Dexamethasone is however associated with lower incidence of vomiting as compared to prednisone. Further homogenous RCTs are needed to provide robust evidence on this topic.

Online link: https://scihubtw.tw/10.1542/hpeds.2013-0088 or https://hosppeds.aappublications.org/content/4/3/172.long

Meta-Analysis

METHODS: A Medline search was conducted on the use of dexamethasone in the treatment of asthma exacerbations in children. The studies selected were clinical trials comparing the efficacy of dexamethasone with prednisone. Meta-analysis was performed examining physician revisitation rates and symptomatic return to baseline.

RESULTS: Six completed pediatric clinical trials met the inclusion criteria. All of the pediatric trials found that prednisone is not superior to dexamethasone in treating mild to moderate asthma exacerbations. Meta-analysis demonstrated homogeneity between the dexamethasone and prednisone groups when examining symptomatic return to baseline and unplanned physician revisits after the initial emergency department encounter. Some studies found potential additional benefits of dexamethasone, including improved compliance and less vomiting.

CONCLUSIONS: The current literature suggests that dexamethasone can be used as an effective alternative to prednisone in the treatment of mild to moderate acute asthma exacerbations in children, with the added benefits of improved compliance, palatability, and cost. However, more research is needed to examine the role of dexamethasone in hospitalized children.

(# of subjects/ studies, cohort definition etc)

-Overall, they looked at 40,257 children who were hospitalized in 42 children’s hospitals for asthma. 1,116 children were given dexamethasone and 39,091 were given prednisone.

-Dexamethasone was given as an either single IM dose or single oral dose during these trials while prednisone was given for 3-6 days at a dosage of 1-2 mg/kg per day.

-Corticosteroid treatment for asthma exacerbation was classified as dexamethasone for children who received dexamethasone only, and as prednisone or for children

who received either prednisone or prednisolone only.

2) Readmission rate of those patients treated with dexamethasone and those treated with prednisone.

3) Treatment cost of acute asthma exacerbation  with dexamethasone vs prednisone.

4) Controlling asthma exacerbations

2) As for readmission rates at 7-30 days, there was no significant difference between the two treatment groups.

3) As for cost, the dexamethasone group had a lower index admission cost when compared to the prednisone group. To be more specific, the median cost in the dexamethasone group was $2621 and in the prednisone group the median cost was $2838.

4) When it came to effectively controlling asthma exacerbations, both groups showed equal effectiveness with no significant difference between the two. There was also no difference in the risk of an asthma relapse at 5, 10-14, or 30 days in both treatment groups.

(2017).

-Patients in the dexamethasone group received 1 oral dose of dexamethasone in the ED, followed by a second dose in 24 hrs. Patients in the prednisone group received a first dose of PO prednisone, followed by 1mg/kg twice daily on days 2-5.

-710 patients met the inclusion criteria for this study but only 590 patients agreed to participate. 294 patients received dexamethasone and the rest of them (296) received prednisone.

-Children were excluded for any of the following reasons: presentation with critical or life-threatening asthma exacerbation, reported use of oral or parenteral corticosteroids in the

previous 4 weeks, or presentation with respiratory failure that

needed further support such as intravenous steroids, intravenous magnesium sulfate, and/or high-flow oxygen and admission to the pediatric intensive care unit

2) Further systematic steroid treatment after treatment with either dexamethasone or prednisone came to an end.

3) Side effects of using prednisone or dexamethasone in children with acute asthma exacerbations.

2) 7.8% of patients in the dexamethasone group needed further systemic steroids when compared to the 6.2% of patients in the prednisone group who also needed further systemic steroid treatment. These differences were deemed not significant by the researchers of this study.

3) As for side effects, the most common one from both treatment groups was emesis. 2.1% of patients in the dexamethasone reported emesis while 4.4% of patients in the prednisone group reported emesis, and this was again deemed not significant by the researchers.

(2014).

-This meta-analysis included a total of 6 RCTs which were all conducted in multiple ED settings. Each of the 6 RCT studies had a mean population of 171 patients with a total population size of 1,026 patients.

-Dexamethasone was given as a single IM dose in 3 studies, a single oral dose in 1 study and as 2 oral doses in the other 2 studies, while prednisone was given as multiple doses in a 5-day course.

2) Rate of hospitalizations after treatment with dexamethasone or prednisone.

3) Difference in relapse rates in both treatment groups.

4) Number of vomiting occurrences in dexamethasone group vs prednisone group.

2) There was also no difference in the rates of hospitalization during the initial ED visit between the two groups.

3) There was no significant difference in the relapse rates in both treatment groups. In the dexamethasone group, there was a 6.6% relapse rate by day 5 and a 13.8% relapse rate by 2 weeks. In the prednisone group, by day 5 the relapse rate was 4.6% and by 2 weeks the relapse rate was 11.9%.

4) Patients in the dexamethasone group were less likely to experience vomiting in either the ED setting or at home than patients in the prednisone group (RR 0.32, 95% CI 0.14– 0.74, Q = 2.38, df = 2, I2 = 4.2%).

-The trials included in this study studied pediatric patients (<18 years old) with acute asthmatic exacerbation who were treated either in ED or ambulatory setting.

-830 patients participated in the dexamethasone group while 824 patients participated in the prednisone group.

– The primary outcome was the relapse rate defined by an unscheduled visit to the ED or clinic. Secondary outcomes were hospital readmission after discharge and incidence of vomiting at ED or home.

-A total of 7 studies (6 RCTs and 1 quasi-RCT) were included in this Systematic Review/ Meta-Analysis. All studies were performed in the ED with varying sample sizes (23–288 patients).

– The dosage of dexamethasone in the included studies was 0.3–0.6 mg/kg with the maximum dose varying from 12 to 18 mg. In comparison, prednisone was administered for 3–5 days at 1–2 mg/kg for a maximum of 30–80 mg across trials.

2) Difference in hospital readmissions after initial discharge.

3) Incident of vomiting in ED.

2) Patients in the dexamethasone group had a re-admission rate of 1.5% while patients in the prednisone group had a re-admission rate of 0.9% which according to the authors of this study this difference was not significant.

3) Those patients who were on dexamethasone reported less frequent vomiting episodes than those patients receiving  prednisone (RR 0.21, 95%CI 0.05–0.96, P = 0.04; I2 = 50%). The frequency of vomiting at home was  significantly higher with prednisone (5.88%) as compared to dexamethasone (2.28%).

systematic reviews, and comparative

and observational studies.

– Meta-analysis was

conducted to compare symptomatic

improvement in the 2 groups (treatment with dexamethasone vs treatment with prednisone) after the

initial ED visit.

-In the end, 6 articles were selected for inclusion in this meta-analysis.

-Primary

outcomes differed between studies

and included relapse rates, patient

and/or parental report of the time

until return to baseline activity, and

changes in asthma scores.

-Participating patients received either a single dose of IM dexamethasone or 5 days of PO prednisolone.

2) Reports of any persistent symptoms that need further medical care.

3) Symptom relapse after 28 days of initial treatment with either dexamethasone or prednisone.

4) Adverse effects reported in the dexamethasone treatment group vs in prednisone treatment group.

5) Compliance rate with medication.

2) After being treated with either dexamethasone or prednisone at the initial ED visits, participating patients were followed up 5 days later by either a clinic visit or telephone. There were no significant differences between the two groups when it came to persistent symptoms that needed further medical care.

3) There was no significant difference between the 2 treatment when it came to relapse symptoms such as cough and wheezing after 28 day follow up.

4) Significant more vomiting episodes were reported in ED for those patients treated with prednisone than those patients who took dexamethasone (3% vs 0.3%; P = 0.008). However, there was no significant difference between the two treatment groups when it came to number of vomiting episodes at home after discharge.

5) The compliance rate was much higher with dexamethasone than with prednisone. This is largely due to the fact that dexameth. can be administered as a single IM dose while prednisone is usually given as a 5-day treatment course.

Another limitation is that in 2 of the studies included in this article had the parents of the participating patient report these data to researcher via telephone which was subjective and therefore can also be bias.