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Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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1
Specific Care Question :
Is dexamethasone better than prednisolone/prednisone for a pediatric asthma exacerbation?
Question Originator: Jeff Michael, DO, FAAP
Plain Language Summary from The Office of Evidence Based Practice:
Children with an asthma exacerbation present to the Emergency Department/Urgent Care Center (ED/UCC) with wheezing, tightness in their
chest and difficulty breathing. Glucocorticosteroids (CS) are a first line medication used to reduce inflammation and reduce the symptoms of asthma. However, CS can have side effects, and reducing the side effects of a treatment is an important goal. The recommendation of the
Asthma in the ED CPG (2012) team is to use prednisone/prednisolone over dexamethasone. It is based on the recommendation of The National
Asthma Education and Prevention Program, Expert Panel Report: Guidelines for the Diagnoses and Management of Asthma (NAEP-EPR-3, 2007). The recommendations of various national and professional society guideline creators were compiled (See Table 1). There is no consensus across
the guidelines on which CS to use for an asthma exacerbation.
There are two major types of CS that can be used. One is dexamethasone and the other is either prednisone (table) prednisolone (syrup). The medications are similar in how well and how quickly they decrease asthma symptoms. Prednisone and/or prednisolone have been the preferred
medications to treat acute asthma because it is believed there are fewer side effects, such as hyperactivity, nausea, and reduced growth.
Dexamethasone is a long acting steroid medication that is 5 times stronger than prednisone/prednisolone and has a longer half-life (Hendeles, 2003). A smaller, less frequent dose of the stronger medication may increase the ability of the child to take the medication.
Therefore, the choice of using one CS over the other is based not on efficacy, but on outcomes that are not well studied, such as believed
compliance to treatment and adverse events including (a) vomiting in the ED, (b) vomiting at home, and (c) adrenal suppression in children with
frequent asthma exacerbations. Since the previous systematic review and abbreviated meta-analysis on this question, three studies (1 RCT and 3 meta-analyses) have been published (Cronin et al., 2015; Keeney et al., 2014; (Meyer, Riese, & Biondi, 2014); Normansell, Kew, & Mansour,
2016). They are added to this critically appraised topic.
Review by Outcome For the comparison PO dexamethasone vs. PO prednisone/olone, (Normansell et al., 2016) includes the studies in (Keeney et al., 2014) and
includes a new study (Cronin et al., 2015). Therefore, Normansell et al. (2016) will be used in this analysis. For the comparison IM
dexamethasone vs. PO prednisone/olone (Keeney et al., 2014) reported on IM plus PO dexamethasone versus PO prednisone/olone. For this analysis, only PO dexamethasone versus PO prednisone will be included. The Risk of Bias Summary is found in Figure 1.
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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The following outcomes are included in this analysis 1. PO dexamethasone vs. PO prednisone/olone
a. Hospital admission at initial presentation
b. Relapse or new exacerbation during the follow up period c. Vomiting
2. IM dexamethasone vs. PO prednisone/olone a. Relapse or new exacerbation during the follow up period
b. Vomiting in the ED
c. Vomiting at home
PO Dexamethasone vs. PO Prednisone/olone Hospital admission at initial presentation. Three studies are included for this outcome (Altamimi et al., 2006; Cronin et al., 2015;
Qureshi, Zaritsky, & Poirier, 2001). The quality of the evidence for this outcome is low. The studies are downgraded for risk of bias (selection, performance, and detection bias). The studies are also downgraded for imprecision since the confidence intervals for the estimate of the effect
cross the line of no effect, and the number of events is low(See Table 2). There is no difference in the odds of being hospitalized at the initial
presentation at the ED for an asthma exacerbation whether treated with PO dexamethasone of PO prednisolone, OR= 1.08, 95% CI [0.74, 1.58] (See Figure 2.).
Relapse or new exacerbation during the follow up period. Four studies are included for this outcome (Altamimi et al., 2006; Cronin et al., 2015; Greenberg, Kerby, & Roosevelt, 2008; Qureshi et al., 2001). The quality of the evidence for this outcome is very low. The
studies are downgraded for risk of bias (selection, performance, and detection bias). The studies are also downgraded for inconsistency as the
follow periods ranged from 5-30 days, and imprecision since the confidence intervals for the estimate of the effect cross the line of no effect, and the number of events is low (See Table 2). There no difference in the odds of having a relapse or new exacerbation during the follow- up periods
whether treated with PO dexamethasone or PO prednisone/olone, OR = 0.85, 95% CI [0.54, 1.34] (See Figure 3). Vomiting. Three studies are included for this outcome (Cronin et al., 2015; Greenberg et al., 2008; Qureshi et al., 2001). The quality of
evidence for this outcome is very low. The studies are downgraded for risk of bias (selection, performance, and detection bias). Since the studies included vomiting in the ED and at home, the studies are also downgraded for inconsistency. Finally, the studies are downgraded for imprecision
since the estimate of the effect crosses the line of no effect, and the number of events is low. There is no difference between vomiting after
treatment with PO dexamethasone or PO prednisone/olone. OR = 0.33, 95% CI [0.09, 1.14] (see Figure 4).
IM dexamethasone vs. PO prednisone/olone Relapse or new exacerbation during the follow up period. Three studies are included in for this outcome (Gordon, Tompkins, &
Dayan, 2007; Gries, Moffitt, Pulos, & Carter, 2000; Klig, Hodge, & Rutherford, 1997). The quality of evidence for this outcome is low. The studies
are downgraded for risk of bias (selection, detection, and performance bias). There are no events of relapse or unscheduled visits to a clinic, ED, or hospital in 2 of the three studies, therefore due to the low number of events; the evidence is downgraded for imprecision; the estimate of the
effect crosses the line of no effect, and the number of events is low. There is no difference in relapse or unscheduled visits after treatment with IM dexamethasone or PO prednisone/olone, OR= 0.71, 95% CI [0.29, 1.74] (See Figure 5).
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Vomiting in the ED. One study is included for this outcome (Gordon et al., 2007) Unable to grade this evidence as there is only one study for this outcome, and the number of events is low. Gordon et al. (2007) shows that the odds of vomiting in the ED significantly less with
dexamethasone OR = 0.05, 95% CI [0.00, 0.87] (See Figure 5). Our confidence in the estimate of the effect is low due to only one study being
included in the body of evidence for vomiting in the ED. Note that Keeney et al (2014) included Altamini (2006) for this outcome. It is excluded from this analysis because data for this outcome was not reported.
Vomiting at home. Two studies are included for this outcome (Gordon et al., 2007 and Altamimi et al., 2006). T he quality of this evidence is low. The studies are downgraded for risk of bias (performance and attrition bias). There are no events of vomiting at home in the
dexamethasone group and only one event of vomiting at home in the prednisone/olone group in each included study. Therefore, due to the very
low number of events, the evidence is downgraded for imprecision. There is no difference in vomiting at home in children treated with IM dexamethasone or PO prednisone/olone, OR = 0.32, 95% CI [0.03, 3.08] (See Figure 6).
EBP Scholar’s responsible for analyzing the literature: Helen Murphy – BHS RRT AE-C
EBP team member responsible for reviewing, synthesizing, and developing this literature:
Nancy H Allen, MS, MLS, RD, LD
Search Strategy and Results:
("Steroids"[Mesh] OR "Glucocorticoids"[Mesh] OR "Glucocorticoids"[Pharmacological Action] OR "dexamethasone 21-phosphate"[Supplementary
Concept] OR "Dexamethasone"[Mesh] OR "Prednisone"[Mesh] OR "Prednisolone"[Mesh] OR "Methylprednisolone"[Mesh]) AND "Asthma/drug therapy"[Majr] AND (("2014/01/01"[PDAT] : "2016/12/31"[PDAT]) AND English[lang] AND ("infant"[MeSH Terms] OR "child"[MeSH Terms] OR
"adolescent"[MeSH Terms]))
104 results
Studies included in this review: (Keeney et al., 2014)
Altamimi et al., 2006
Gordon, Tompkins, & Dayan, 2007 Greenberg, Kerby, & Roosevelt, 2008
Klig, Hodge, & Rutherford, 1997
Qureshi, Zaritsky, & Poirier, 2001 (Meyer et al., 2014)
Altamimi et al., 2006 Gordon, Tompkins, & Dayan, 2007
Gries, et al., 2000
Greenberg, Kerby, & Roosevelt, 2008 Klig, Hodge, & Rutherford, 1997
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Qureshi, Zaritsky, & Poirier, 2001 (Normansell et al., 2016)
Altamimi et al., 2006
Cronin et al., 2015 Gordon et al. 2007
Greenberg, Kerby, & Roosevelt, 2008 Qureshi, Zaritsky, & Poirier, 2001
Hendeles (2003) is used as background information Studies not included in this review with rationale for exclusion:
Study Reason for Exclusion
Cross 2011 Narrative review
Goleva 2012 Cohort study of steroid resistant vs. steroid sensitive
Shefrin 2009 Narrative review
Sutherland 2008 Does not answer the question. Outcome include non-smoking adult lung function, BMI, and spirometric response to
medication
(Watnick, Fabbri, &
Arnold, 2016)
Cohort study
Method Used for Appraisal and Synthesis: The Cochrane Collaborative computer program, Review Manager (RevMan 5.3.5), was used to synthesize the XXX included studies.
Updated: May 27 2016; June 8 2016
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Table 1
Guideline Comparison: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
Guidelines Prednisone Dexamethasone
EPR 3 2007
Recommendation based
on Hendeles (2003)
Prefers prednisone over dexamethasone
Does not mention dexamethasone for an exacerbation.
For long term control medications it states dexamethasone is likely to be as effective as prednisolone. It goes on to say: --
or patients unable to tolerate the liquid preparations,
dexamethasone syrup at 0.4 mg/kg/d may be an alternative. Studies are limited, however, and the longer duration of
activity increases the risk of adrenal suppression
Canadian guideline Prednisone/prednisolone (oral)
Dose:1-2 mg/kg (max 50 mg)
Duration: 3 to 5 days
Does not mention dexamethasone
Colorado 2011
Treat with Prednisone(or equivalent)
Dose: 2 mg/kg orally (80 mg max for inpatient) Dose: 2 mg/kg orally (60 mg max for outpatient)
Duration 3-10 days
Does not mention dexamethasone
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Seattle Children’s
Hospital
Recommendation based
on Keeney et al. (2014) and Meyer et al.
(2014)
Prednisone or equivalents for Inpatient use Prednisone
Dose:2 mg/kg/d PO QD Max60 mg Duration: 5-10 days of total steroids
Prednisolone
Dose :2 mg/kg/d PO QD Max 60 mg Duration: 5-10 days of total steroids
Methylprednisolone Dose: 1 mg/kg. IV q 6 (Max 60 mg per dose)
Duration: not stated
Dexamethasone for ED use
Dose: 0.6 mg/kg/d PO QD (16 mg max dose) Duration not stated
Should be given within one hour of entering the ED
Children’s Hospital of Philadelphia
Emergency Department
Recommendation made
based on Keeney et al. (2014)
Severe: ESI 1-2
Prednisone/olone/Methylprednisolone Dose:
Prednisone/ Methylprednisolone: 2 mg/kg p.o./IV MAX 60
mg Duration: not stated
Mild: ESI Triage 4
Consider dexamethasone tablet (alternative prednisone/olone) Moderate: ESI Triage 3
Dexamethasone tablet (alternative prednisone/olone) Dose:
Dexamethasone: Mild to moderate flare, ,
5-8 years 4 mg
>8-12 years
6 mg
> 12 years
8 mg
Duration: repeat in 24-48 hours
Children’s Hospital of
Philadelphia Inpatient
Steroid management: prednisone/prednisolone q 12 hours
after initial systemic corticosteroid administration discontinued inhaled corticosteroid.
Severe:
Continue prednisone/prednisolone/ Methylprednisolone Moderate:
Continue prednisone/prednisolone
Mild: Continue prednisone
Does not mention dexamethasone
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Global Initiative for
Asthma (GINA) 2015
For children, an OCS dose of 1–2 mg/kg up to a maximum of
40 mg/day is adequate.
Oral dexamethasone for 2 days can also be used, but there
are concerns about metabolic side effects if it is continued beyond 2 days
British Thoracic Society/ Scottish Intercollegiate
Guidelines Network (BTS/SIGN)
2014
Oral prednisone is the steroid of choice for asthma attacks in
children unless the patient is unable to tolerate the dose 2-5 years 20 mg/kg
>5 years 30-40 mg Intravenous hydrocortisone (4 mg/kg, repeated four hourly)
should be reserved for severely affected children who are
unable to retain oral medication
Insufficient evidence to suggest that dexamethasone offers an advantage over prednisolone
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Table 2
Grade Summary of Normansell et al. (2016) Question: Should dexamethasone be used in acute asthma exacerbation in children?
Studies included in the meta-analysis: (Altamimi et al., 2006; Cronin et al., 2015; Gordon et al. 2007; Greenberg, Kerby, & Roosevelt, 2008; Qureshi, Zaritsky, & Poirier, 2001)
Quality assessment № of patients Effect
Quality № of studies
Study design
Risk of
bias Inconsistency Indirectness Imprecision
Other considerations
Oral dexamethasone
Prednisone Relative
(95% CI)
Absolute (95%
CI)
Hospital admission at initial presentation
3 randomized trials
serious 1
not serious not serious serious 2 none 63/508 (12.4%) 58/499 (11.6%)
OR 1.08 (0.74 to 1.58)
8 more per
1,000 (from 28 fewer to 56 more)
⨁⨁◯◯
LOW
New exacerbation during the follow-up period
4 randomized trials
serious 1
not serious not serious serious 2 none 39/475 (8.2%) 49/506 (9.7%)
OR 0.85 (0.54 to
1.34)
13 fewer
per 1,000
(from 29 more to
42 fewer)
⨁⨁◯◯
LOW
Vomiting
3 randomized trials
serious 1
not serious not serious serious 2 none 11/446 (2.5%) 32/421 (7.6%)
- 50 fewer per
1000 (from (0.69
fewer to 10 more)
⨁⨁◯◯
LOW
CI: Confidence interval; OR: Odds ratio; MD: Mean difference
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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1. Downgraded once for risk of bias, Cronin et al. (2015) 8% of subjects were enrolled twice. Quereshi et al. (2001) was considered to be at high or unclear risk of selection bias, while performance and detection bias were noted in both Qureshi et al. (2001) and Cronin et al. (2015).
2. Confidence cross the line of no effect; unsure if a clinically important event is present, and which treatment it favors
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Table 3
Grade Summary of (Keeney et al. (2014) Question: Should dexamethasone be used in acute asthma exacerbation in children?
Studies included in the meta-analysis: (Altamimi et al., 2006; Gordon, Tompkins, & Dayan, 2007; Greenberg, Kerby, & Roosevelt, 2008; Klig, Hodge, & Rutherford, 1997; Qureshi, Zaritsky, & Poirier, 2001)
Quality assessment Summary of findings
Importance No of patients Effect
Quality No of
studies Design Limitations Inconsistency Indirectness Imprecision
Other
considerations
Dexa-
methasone control
Relative (95%
CI)
Absolute
Relapse rate 5 days (follow-up 5 days; number who returned for treatment of exacerbation)
4 randomized trials
serious1,2 serious3,4 no serious indirectness
no serious imprecision
none
14/167
(8.4%)
15/169
(8.9%)
RR 0.90
(0.46 to 1.78)
9 fewer per 1000
(from 48 fewer to
69 more)
⨁⨁OO
LOW CRITICAL
Relapse rate 10-14 days (follow-up 10-14 days; number who returned for treatment of exacerbation)
3 randomized
trials
serious1,2 serious3,4 no serious
indirectness
no serious
imprecision
none
47/391
(12%)
40/372
(10.8%)
RR 1.13
(0.77 to 1.67)
14 more
per 1000
(from 25 fewer to
72 more)
⨁⨁OO
LOW CRITICAL
Vomiting in the ED (follow-up 2-4 hours)
4 randomized
trials
serious1,2 serious3,4 no serious
indirectness
no serious
imprecision
none
6/506
(1.2%)
27/511
(5.3%)
RR 0.29 (0.12 to
0.69)
38 fewer
per 1000 (from 16
fewer to
46 fewer)
⨁⨁OO
LOW IMPORTANT
1 There is poor reporting of allocation concealment in half of the studies. 2 One third of the studies blinded the participants, and in only one study were outcome assessors blinded. 3 The I2 statistic low (0- 18.7) but there were differences in the treatments, Three studies used a single IM dose of dexamethasone, one study used a single oral dose and two studies used multiple oral doses. 4 The dose of IM dexamethasone ranged from 0.3 mg/kg with a mix of 15 mg IM X 1 dose to 1.7 mg/kg 1.7 mg/kg (max 36 mg) IM X 1 dose. The range of oral dexamethasone ranged from 0.3 mg/kg (max 15 mg) PO X 1 dose to 0.6 mg/kg (max 16 mg) PO once daily X 2 days.
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Figures:
Figure 1. Risk of bias summary
Rand
om s
eque
nce
gene
ratio
n (s
elec
tion
bias
)
Altamimi 2006 +
Cronin 2015 –
Gordon 2007 +
Greenberg 2008 ?
Gries 2000 ?
Klig 1997 +
Qureshi 2001 –
Allo
catio
n co
ncea
lmen
t (se
lect
ion
bias
)
+
?
+
+
–
?
–
Blin
ding
(per
form
ance
bia
s an
d de
tect
ion
bias
)
+
–
–
+
?
–
–
Inco
mpl
ete
outc
ome
data
(attr
ition
bias
)
–
?
–
+
?
?
–
Sele
ctive
repo
rting
(rep
ortin
g bi
as)
+
?
+
?
?
–
?
Oth
er b
ias
–
?
–
+
–
?
?
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Figure 2. Oral dexamethasone vs. oral prednisone/olone, Outcome: Hospital admission at initial presentation
Figure 3. Oral dexamethasone vs. oral prednisone/olone, Outcome: New exacerbation during the follow up period
Study or Subgroup
Altamimi 2006
Cronin 2015
Qureshi 2001
Total (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 0.81, df = 2 (P = 0.67); I² = 0%
Test for overall effect: Z = 0.00 (P = 1.00)
Events
6
18
34
58
Total
67
123
309
499
Events
9
16
34
59
Total
67
122
319
508
Weight
12.5%
28.4%
59.1%
100.0%
M-H, Random, 95% CI
0.63 [0.21, 1.89]
1.14 [0.55, 2.35]
1.04 [0.63, 1.71]
1.00 [0.68, 1.47]
Dexamethasone Predinisone/olone Odds Ratio
Risk of bias legend
(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding (performance bias and detection bias)
(D) Incomplete outcome data (attrition bias)
(E) Selective reporting (reporting bias)
(F) Other bias
+ + + – + –
– ? – ? ? ?
– – – – ? ?
Risk of Bias
A B C D E F
Odds Ratio
M-H, Random, 95% CI
0.005 0.1 1 10 200
PO Dexamethasone PO Prednisone/olone
Study or Subgroup
Altamimi 2006
Cronin 2015
Greenberg 2008
Qureshi 2001
Total (95% CI)
Total events
Heterogeneity: Tau² = 0.00; Chi² = 2.16, df = 3 (P = 0.54); I² = 0%
Test for overall effect: Z = 0.70 (P = 0.48)
Events
4
17
8
20
49
Total
61
122
51
272
506
Events
1
17
3
18
39
Total
56
120
38
261
475
Weight
4.1%
38.8%
10.4%
46.7%
100.0%
M-H, Random, 95% CI
3.86 [0.42, 35.62]
0.98 [0.48, 2.03]
2.17 [0.54, 8.80]
1.07 [0.55, 2.07]
1.17 [0.75, 1.85]
Dexamethasone Predinisone/olone Odds Ratio
Risk of bias legend
(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding (performance bias and detection bias)
(D) Incomplete outcome data (attrition bias)
(E) Selective reporting (reporting bias)
(F) Other bias
+ + + – + –
– ? – ? ? ?
? + + + ? +
– – – – ? ?
Risk of Bias
A B C D E F
Odds Ratio
M-H, Random, 95% CI
0.01 0.1 1 10 100
Dexamethasone Prednisone/olone
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Figure 4. Oral dexamethasone vs. oral prednisone/olone, Outcome: Vomiting
Study or Subgroup
Cronin 2015
Greenberg 2008
Qureshi 2001
Total (95% CI)
Total events
Heterogeneity: Tau² = 0.62; Chi² = 4.29, df = 2 (P = 0.12); I² = 53%
Test for overall effect: Z = 1.76 (P = 0.08)
Events
0
5
6
11
Total
123
51
272
446
Events
14
7
11
32
Total
122
38
261
421
Weight
14.9%
39.6%
45.5%
100.0%
M-H, Random, 95% CI
0.03 [0.00, 0.51]
0.48 [0.14, 1.65]
0.51 [0.19, 1.41]
0.33 [0.09, 1.14]
Dexamethasone Predinisone/olone Odds Ratio
Risk of bias legend
(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding (performance bias and detection bias)
(D) Incomplete outcome data (attrition bias)
(E) Selective reporting (reporting bias)
(F) Other bias
– ? – ? ? ?
? + + + ? +
– – – – ? ?
Risk of Bias
A B C D E F
Odds Ratio
M-H, Random, 95% CI
0.01 0.1 1 10 100
PO Dexamethasone PO Prednisone/olone
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Figure 5. IM Dexamethasone vs. oral prednisone/olone Outcome: Vomiting in the ED
Figure 6. Figure 5. IM Dexamethasone vs. oral prednisone/olone Outcome: Vomiting at home
Study or Subgroup
Gordon 2007
Total (95% CI)
Total events
Heterogeneity: Not applicable
Test for overall effect: Z = 2.06 (P = 0.04)
Events
0
0
Total
89
89
Events
9
9
Total
93
93
Weight
100.0%
100.0%
M-H, Fixed, 95% CI
0.05 [0.00, 0.87]
0.05 [0.00, 0.87]
Dexamethasone Prednisone/olone Odds Ratio
Risk of bias legend
(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding (performance bias and detection bias)
(D) Incomplete outcome data (attrition bias)
(E) Selective reporting (reporting bias)
(F) Other bias
+ + – – + –
Risk of Bias
A B C D E F
Odds Ratio
M-H, Fixed, 95% CI
0.001 0.1 1 10 1000
IM Dexamethasone PO Predinsione/olone
Study or Subgroup
Altamimi 2006
Gordon 2007
Total (95% CI)
Total events
Heterogeneity: Chi² = 0.00, df = 1 (P = 1.00); I² = 0%
Test for overall effect: Z = 0.99 (P = 0.32)
Events
0
0
0
Total
56
57
113
Events
1
1
2
Total
54
55
109
Weight
50.0%
50.0%
100.0%
M-H, Fixed, 95% CI
0.32 [0.01, 7.92]
0.32 [0.01, 7.92]
0.32 [0.03, 3.08]
Dexamethasone Prednisone/olone Odds Ratio
Risk of bias legend
(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding (performance bias and detection bias)
(D) Incomplete outcome data (attrition bias)
(E) Selective reporting (reporting bias)
(F) Other bias
+ + + – + –
+ + – – + –
Risk of Bias
A B C D E F
Odds Ratio
M-H, Fixed, 95% CI
0.01 0.1 1 10 100
IM Dexamethasone PO Predinsione/olone
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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References
Altamimi, S., Robertson, G., Jastaniah, W., Davey, A., Dehghani, N., Chen, R., . . . Colbourne, M. (2006). Single-dose oral dexamethasone in the emergency management of children with exacerbations of mild to moderate asthma. Pediatr Emerg Care, 22(12), 786-793.
doi:10.1097/01.pec.0000248683.09895.0800006565-200612000-00003 [pii]
Cronin, J. J., McCoy, S., Kennedy, U., An Fhaili, S. N., Wakai, A., Hayden, J., . . . O'Sullivan, R. (2015). A Randomized Trial of Single-Dose Oral Dexamethasone Versus Multidose Prednisolone for Acute Exacerbations of Asthma in Children Who Attend the Emergency Department.
Ann Emerg Med. doi:10.1016/j.annemergmed.2015.08.001 Gordon, S., Tompkins, T., & Dayan, P. S. (2007). Randomized trial of single-dose intramuscular dexamethasone compared with prednisolone for
children with acute asthma. Pediatr Emerg Care, 23(8), 521-527. doi:10.1097/PEC.0b013e318128f82100006565-200708000-00001 [pii] Greenberg, R. A., Kerby, G., & Roosevelt, G. E. (2008). A comparison of oral dexamethasone with oral prednisone in pediatric asthma
exacerbations treated in the emergency department. Clin Pediatr (Phila), 47(8), 817-823.
doi:10.1177/00099228083169880009922808316988 [pii] Gries, D. M., Moffitt, D. R., Pulos, E., & Carter, E. R. (2000). A single dose of intramuscularly administered dexamethasone acetate is as effective
as oral prednisone to treat asthma exacerbations in young children. J Pediatr, 136(3), 298-303. doi:10.1067/mpd.2000.103353 Hendeles, L. (2003). Selecting a systemic corticosteroid for acute asthma in young children. J Pediatr, 142(2 Suppl), S40-44.
Keeney, G. E., Gray, M. P., Morrison, A. K., Levas, M. N., Kessler, E. A., Hill, G. D., . . . Jackson, J. L. (2014). Dexamethasone for acute asthma
exacerbations in children: a meta-analysis. Pediatrics, 133(3), 493-499. doi:10.1542/peds.2013-2273 Klig, J. E., Hodge, D., 3rd, & Rutherford, M. W. (1997). Symptomatic improvement following emergency department management of asthma: a
pilot study of intramuscular dexamethasone versus oral prednisone. J Asthma, 34(5), 419-425. Lougheed, M. D., Lemiere, C., Ducharme, F. M., Licskai, C., Dell, S. D., Rowe, B. H., . . . Canadian Thoracic Society Asthma Clinical, A. (2012).
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Meyer, J. S., Riese, J., & Biondi, E. (2014). Is dexamethasone an effective alternative to oral prednisone in the treatment of pediatric asthma
exacerbations? Hosp Pediatr, 4(3), 172-180. doi:10.1542/hpeds.2013-0088 NAEP-EPR-3. (2007). Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. Bethesda MD: U.S. Department of Health
and Human Services, National Institutes of Health. Normansell, R., Kew, K. M., & Mansour, G. (2016). Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev, 5,
CD011801. doi:10.1002/14651858.CD011801.pub2
Qureshi, F., Zaritsky, A., & Poirier, M. P. (2001). Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. The Journal of pediatrics, 139(1), 20-26. doi:10.1067/mpd.2001.115021
Watnick, C. S., Fabbri, D., & Arnold, D. H. (2016). Single-dose oral dexamethasone is effective in preventing relapse after acute asthma exacerbations. Ann Allergy Asthma Immunol, 116(2), 171-172. doi:10.1016/j.anai.2015.11.015
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Appendix
Understanding GRADE (Grading of Recommendations Assessment, Development, and Evaluation)
The following concepts are utilized when applying GRADE to a literature analysis that answers a clinical question. The quality of the evidence (High, Medium, Low, or Very Low) reflects the confidence in the estimate of effect for an outcome to support the recommendation.
When the evidence is only from RCTs the GRADE starts as High quality evidence.
The RCTs are read and assessed upon the criteria below. Risk of Bias, looks specifically for:
o Randomization
o Concealment of allocation o Blinding (participants, providers, outcome assessor)
o How subjects who did not complete the study were handled o Selective reporting
Inconsistency (heterogeneity) is present when:
o Variation of point estimates across the included studies is reported?
o The confidence intervals of the included studies do not overlap, or have minimal overlap o The p value of the statistical tests for heterogeneity (Chi2) is low (p< 0.05)
o The I2 statistic is roughly interpreted as (note the overlap in the ranges below; I2 is not a precise measure): 0%-40% the heterogeneity might not be a factor
30-60% may indicate moderate heterogeneity
50-90% may indicate substantial heterogeneity 75-100% indicates considerable heterogeneity
Indirectness is present when:
o Studies with a direct comparison are not available, and the included studies are combined to indirectly look at the comparison of interest. Example: The Migraine in the Emergency Department Clinical Practice Guideline compares dexamethasone to magnesium
sulfate IV for the outcome pain relief at 2 hours. Studies have been identified that compare (a) dexamethasone to magnesium sulfate (IV), and (b) prochlorperazine to magnesium sulfate (IV). If they are used to compare dexamethasone to prochlorperazine
the evidence is indirect. (See Figure A1)
o Studies predominantly include (a) participants, (b) methods- such as doses, (c) outcomes that are different from the question asked by the guideline panel. In pediatrics, this is most often seen when adult population studies are applied to children.
Imprecision is present when:
o The included studies have less than ~ 400 subjects cumulatively (this is a rule of thumb) o The included studies have a small number of events. For example, for the outcome mortality, if there are only 2 deaths across all
studies, the evidence will be downgraded for imprecision.
o The 95% confidence interval of the cumulative effect includes the line of no effect and the confidence intervals of the included study are wide
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Publication Bias is evident when:
o Literature is systematically over- or underestimate of the treatment effect due to which studies are selected for publication
Studies with small sample sizes are less likely to be published Negative studies are less likely to be published
All the studies have strong links to commercial enterprises that might benefit from the results o Publication bias is assessed by evaluating funnel plots
EXAMPLE
For each criterion, if present, the quality of evidence is reduced by one. For example, four studies have been located for the comparison dexamethasone versus magnesium sulfate (IV) to treat refractory migraine in the ED. The outcome is Hospitalization. The studies start as High
quality for grading summary (See Table A1). The studies have:
Risk of Bias- the study is methodologically strong- Low risk of bias- not downgraded
Inconsistency- confidence intervals overlap and the I2 is 0%- Low risk of inconsistency- not downgraded (See Figure A2)
Indirectness- no direct comparison, extrapolated from comparison to another drug- High risk of indirectness- downgraded to Moderate
Imprecision- there are four studies, the cumulative number of subjects is 299, and the number of events (number of subjects hospitalized
is 11). Imprecision is high because (a) the effect size crosses the line of no effect, and (b) the number of subjects and the number hospitalized are low, therefore the evidence has High risk of imprecision- downgraded to Low (See Figure A2.)
Publication Bias- unable to assess, only four small studies are included- Stays at Low
For this outcome, using the GRADE criteria, the quality of evidence for this comparison is Low.
Table A1. Grade Summary for the Example
Quality of Evidence for this Outcome GRADE
High Starting point Moderate Downgrade to Moderate due to Indirectness
Low Downgrade to Low due to Imprecision Very Low
Note: this evidence was not downgraded for risk of bias, inconsistency or publication bias.
Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation
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Figure A1. Example of Indirectness
Figure A2. Meta-analysis example for Grade
Reference: Schünemann H, Santesso, N. (2016). How to GRADE the Evidence. Retrieved from http://training.cochrane.org/
Dexamethasone
vs.
Prochlorperazine
Prochlorperazine vs. Magnesium Sulfate IV
Dexamethasone vs. Magnesium Sulfate IV
Study or Subgroup
STUDY 1
STUDY 2
STUDY 3
STUDY 4
Total (95% CI)
Total events
Heterogeneity: Chi² = 0.95, df = 3 (P = 0.81); I² = 0%
Test for overall effect: Z = 0.03 (P = 0.98)
Events
1
1
2
2
6
Total
30
37
40
52
159
Events
1
2
1
1
5
Total
36
29
26
49
140
Weight
16.9%
41.6%
22.5%
19.1%
100.0%
M-H, Fixed, 95% CI
1.20 [0.08, 18.38]
0.39 [0.04, 4.11]
1.30 [0.12, 13.62]
1.88 [0.18, 20.13]
1.02 [0.32, 3.25]
TREATMENT A TREATMENT B Risk Ratio Risk Ratio
M-H, Fixed, 95% CI
0.01 0.1 1 10 100
TREATMENT A TREATMENT B
Indirect comparison