Epinephrine for bronchiolitis

L Hartling, N Wiebe, K Russell, H Patel, T P Klassen
Cochrane Database of Systematic Reviews 2004, (1): CD003123

BACKGROUND: Bronchodilators are commonly used in the management of bronchiolitis. A recent systematic review showed that bronchodilators produce modest short-term benefit among patients with mild or moderate bronchiolitis.

OBJECTIVES: To compare epinephrine versus placebo and other bronchodilators in infants less than 2 years of age with bronchiolitis.

SEARCH STRATEGY: Electronic searches were conducted on the following bibliographic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to May 2003), and EMBASE (January 1988 to May 2003). The reference lists of all selected articles were examined for relevant studies. Primary authors were contacted for information on additional trials.

SELECTION CRITERIA: Studies were included if they: 1) were RCTs comparing epinephrine with placebo or other bronchodilator; 2) involved children less than two years with bronchiolitis; 3) presented at least one quantitative outcome.

DATA COLLECTION AND ANALYSIS: Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted by one reviewer using a structured form and checked by a second. Separate analyses were conducted for the two types of control groups (placebo, non-epinephrine bronchodilators) and for patient status (inpatient, outpatient).

MAIN RESULTS: Fourteen studies were included. Quality ranged from one to five (Jadad scale) with a median of three (inter-quartile range: two to three). Allocation concealment was adequate in six trials and unclear in eight. Among inpatient studies comparing epinephrine and placebo (n = five), there was one significant outcome favouring epinephrine: change in clinical score at 60 minutes post-treatment (SMD -0.52; 95% CI -1.00,-0.03). For outpatient studies (n = three), change in clinical score at 60 minutes (SMD -0.81; -1.56,-0.07), change in oxygen saturation at 30 minutes (WMD 2.79;1.50,4.08), respiratory rate at 30 minutes (WMD -4.54;-8.89-0.19), and "improvement" (OR 25.06; 4.95,126.91) favoured epinephrine. Heart rate at 60 minutes post-treatment favoured placebo (WMD 11.80; 5.20,18.40). Admission rates and change in oxygen saturation at 60 minutes post-treatment were not significantly different. For inpatient studies comparing epinephrine and salbutamol (n = four), only one of the seven outcomes was statistically significant: respiratory rate at 30 minutes favoured epinephrine (WMD -5.12; -6.83;-3.41). Among outpatient studies (n = four), change in oxygen saturation at 60 minutes (WMD 1.91; 0.38,3.44), heart rate at 90 minutes (WMD -14.00; -22.95;-5.05), respiratory rate at 60 minutes (WMD -7.76; -11.35,-4.17) post-treatment and "improvement" (OR 4.51; 1.93,10.53) favoured epinephrine. Admission rates were not significantly different (OR 0.40; 0.12,1.33). Pallor at 30 minutes post-treatment was significantly higher in the epinephrine group (OR 6.00; 1.33,27.00).

REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among inpatients. There is some evidence to suggest that epinephrine may be favourable to salbutamol and placebo among outpatients. A number of large, multi-centered trials are required to examine the effectiveness of epinephrine compared to placebo and salbutamol for infants presenting to outpatient settings. There is a need to develop a validated, reliable scoring system that is sensitive to important clinical changes in patients with bronchiolitis.

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