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Methylprednisolone IV

Question 7:

In the child hospitalized with an asthma exacerbation, should methylprednisolone/ prednisolone/prednisone vs. dexamethasone be used to improve pulmonary function?


Inpatient asthma team recommendation: Based on high quality evidence, we recommend a 5-day course of oral prednisolone/prednisone for acute asthma exacerbations. The National guideline (EPR-3, 2007) states dexamethasone is not preferred due to the increased duration of drug activity that increases the risk of adrenal suppression. For this recommendation, we placed a high value on decreasing unscheduled re-evaluations, re- admissions, and cost of treatment. 

Literature (see Appendix D) supporting this recommendation:
Since EPR-3 (2007) a meta- analysis of six studies by Keeney et al. (2014) reported that relapse rate at 5 days and 10-14 days post treatment for asthma exacerbation were similar for children treated with dexamethasone or prednisolone/prednisone. The forest plots of the studies included in Keeney are included in Figures 2 and 4. In addition, they reported that vomiting was significantly less in the groups treated with dexamethasone. GRADing the Keeney et al., (2014) paper shows the following (see Table 3 and Table 4). 

For the vomiting comparison, treatment with dexamethasone was intramuscular in three of the four studies, while treatment with prednisolone/prednisone was PO in all studies. Prednisolone/prednisone doses were either singular or multiple oral doses

  1. Doses of corticosteroids varied widely across studies:

    • 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 (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.

  2. The studies were not powered on the outcome vomiting. 

Therefore, the asthma inpatient team does not recommend the use of dexamethasone over prednisolone/prednisone at this time. Future research will change our confidence in the estimate of the effect. 


Tables

TABLE 3
GRADE assessment of studies included in (Keeney et al., 2014).

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, 3 studies used a single IM dose of dexamethasone, 1 study used a single oral dose and 2 studies used multiple oral doses. 
4 The dose of IM dexamethasone ranged from 0.3 mg/kg with a maximum 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.
5Low number of subjects and low number of events 


Table 4 
Dose and duration of Intervention and Comparison of the studies included in Keeney et al., (2014

Author

Intervention

Comparison

Single IM dose

 

 

(Gries, Moffitt, Pulos, & Carter, 2000)

Dexamethasone 1.7 mg/kg (max 36 mg) IM X 1 dose

Prednisone or prednisolone 1 mg/kg (max 20 mg) PO twice daily X 5 days

(Gordon, Tompkins, & Dayan, 2007)

Dexamethasone 0.6 mg/kg (max 15 mg) IM X 1 dose

Prednisolone 2 mg/kg (max 50 mg) PO daily X 5 days

(Klig, Hodge, & Rutherford, 1997)

Dexamethasone 0.3 mg/kg (max 15 mg) IM X 1 dose

Prednisone 2 mg/kg (max 100 mg) PO X 1 dose, then 1 mg/kg PO daily  X 2 days

Single Oral Dose

 

 

(Altamimi et al., 2006)

Dexamethasone 0.6 mg/kg (max 18 mg) PO X 1 dose, then placebo PO twice daily for 5 days

Prednisone or prednisolone 1 mg/kg (max 30 mg) PO X 1 dose, then 1 mg/kg PO twice daily X 5 days

Multiple Oral Dose

 

 

(Greenberg, Kerby, & Roosevelt, 2008)

Dexamethasone 0.6 mg/kg (max 16 mg) PO once daily X 2 days

Prednisone 2 mg/kg (max 80 mg) PO X 1 dose, then 1 mg/kg(max 30 mg) PO twice daily  X 4 days

(Qureshi, Zaritsky, & Poirier, 2001)

Dexamethasone 0.6 mg/kg (max 16 mg) PO once daily X 2 days

Prednisone or prednisolone 2 mg/kg (max 60 mg) PO X 1 dose, then 1 mg/kg (max 60 mg) PO daily X 4 days


Figures

Figure 2. Dexamethasone vs. Prednisone/prednisolone, Outcome Relapse. All studies except Gordon et al. (2007) compare administration by mouth. Gordon et al. (2007) compared dexamethasone intramuscularly vs. prednisone/prednisolone by mouth.

Figure 3. Dexamethasone vs. Prednisone/Prednisolone, Outcome Vomiting in the ED. All studies except Gordon et al., (2007) compare administration by mouth. Gordon et al., (2007) compared dexamethasone intramuscularly vs. prednisone/prednisolone by mouth.

Figure 3a. Dexamethasone vs. Prednisone/Prednisolone, Outcome Vomiting in the ED (Gordon et al., 2007)

Figure 4. Dexamethasone vs. Prednisone/Prednisolone, Outcome Vomiting at home. All studies except Gordon et al., (2007) compare administration by mouth. Gordon et al., (2007) compared dexamethasone intramuscularly vs. prednisone/prednisolone by mouth.

These guidelines do not establish a standard of care to be followed in every case. It is recognized that each case is different and those individuals involved in providing health care are expected to use their judgment in determining what is in the best interests of the patient based on the circumstances existing at the time. It is impossible to anticipate all possible situations that may exist and to prepare guidelines for each. Accordingly these guidelines should guide care with the understanding that departures from them may be required at times.