office of evidence based practice specific care question ...€¦ · or = 0.33, 95% ci [0.09, 1.14]...

Office of Evidence Based Practice – Specific Care Question: Dexamethasone vs. Prednisone for a Pediatric Asthma Exacerbation

If you have questions regarding this Specific Care Question – please contact [email protected]

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.

mailto:[email protected]



2

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).




3

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




4

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




5

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





6

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





7

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




8

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


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


- 50 fewer per

1000 (from (0.69

fewer to 10 more)

⨁⨁◯◯

LOW

CI: Confidence interval; OR: Odds ratio; MD: Mean difference




9

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




10

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.




11

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

–

?

–

+

–

?

?




12

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



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]


Risk of bias legend






(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




13

Figure 4. Oral dexamethasone vs. oral prednisone/olone, Outcome: Vomiting

Study or Subgroup

Cronin 2015

Greenberg 2008

Qureshi 2001

Total (95% CI)

Total events



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]


Risk of bias legend






(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




14

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


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






(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%


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






(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




15

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).

Canadian Thoracic Society 2012 guideline update: Diagnosis and management of asthma in preschoolers, children and adults: Executive summary. Canadian Respiratory Journal : Journal of the Canadian Thoracic Society, 19(6), e81-e88.

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




16

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




17

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.




18

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%


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


office of evidence based practice specific care question ...€¦ · or = 0.33, 95% ci [0.09, 1.14]...

Documents