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There is moderate quality evidence that inhaled epinephrine substantially improves short-term outcomes for outpatients presenting with bronchiolitis, when bronchiolitis is defined as the first episode of wheezing in children under two years of age. Epinephrine substantially reduces hospital admissions within the first day of treatment, and these findings are supported by positive results from other clinical outcomes, especially an improvement in clinical score within the first one and two hours of treatment. Most direct comparisons between epinephrine and other active interventions (bronchodilators and glucocorticoids) were not significant, and compared to placebo, neither bronchodilators nor glucocorticoids improved short-term outcomes. In this overview, we did not include outpatient measures of clinical severity at 24, 48 or 72 hours, as these time-points are often too delayed to be clinically relevant in an outpatient setting. However, it is worth noting that for outpatients with bronchiolitis, 3 hypertonic saline leads to large, statistically significant reductions in clinical severity at all three of the indicated time-points (78). Results suggest that combining inhaled epinephrine with the systemic glucocorticoid dexamethasone (as opposed to stand-alone therapy with either drug alone) may be effective in improving the longer-term outcome of outpatient admissions within seven days. However, this finding should be interpreted with caution as this conclusion was based on a small number of events from a single trial, therefore resulting in low strength of evidence. These positive results should be balanced against data on harms. There are safety concerns when considering the widespread use of epinephrine, and especially glucocorticoids, in young children with viral wheezing. High-dose glucocorticoids (i.e. dexamethasone), such as the dosages used in the glucocorticoid and epinephrine reviews (0.6–1.0 mg/kg), are potentially dangerous, and the effects of glucocorticoids and/or epinephrine on children with comorbid illnesses are currently unknown (83,84). The results from the randomized control trials (RCTs) included in this overview do not suggest any serious short-term adverse effects of epinephrine administered either with or without glucocorticoids, and data from RCTs and observational studies on a related illness – croup – also suggest a favorable short-term safety profile for both epinephrine and dexamethasone (85,86). However, it should be noted that no studies had long-term follow-ups assessing the harms of glucocorticoids, and many of the studies would have been unable to detect important differences in adverse events due to limited power. Furthermore, RCTs do not adequately address all drug safety concerns (87). In summary, epinephrine is the most effective treatment for outpatients presenting with bronchiolitis, and appears to be superior to both bronchodilators and glucocorticoids. The benefits and risks of adding glucocorticoids to epinephrine for longer-term benefits needs to be further clarified, along with whether results from combination therapies are generalizable to lower doses of glucocorticoids and glucocorticoids other than dexamethasone. The above findings likely apply to outpatients presenting to the emergency department with moderate to severe bronchiolitis.
This overview presents the most current Cochrane evidence regarding the efficacy and safety of interventions for acute viral bronchiolitis in different treatment settings. Treatment of bronchiolitis is a controversial topic in pediatrics, and current best practice guidelines recommend supportive measures as the mainstay of management (9,57,58). In both ambulatory and hospital settings, this includes adequate oxygenation combined with attention to nasal obstruction, fluid intake and nutrition. However, there are many additional therapies that clinicians try in an effort to reduce the tremendous number of hospital admissions, and this may explain the wide variation in bronchiolitis treatment, despite the absence of clear evidence for many therapeutic approaches. Recent evidence presented in this overview provides some clarity as to the current most effective interventions for outpatients, inpatients, and ICU patients. This evidence must be weighed against possible harms, and its interpretation must be viewed in light of the methodological limitations of research within the field.
For inpatients, epinephrine versus bronchodilator led to a significantly lower clinical score at both 60 minutes (4 trials; 248 participants) and 120 minutes (1 trial; 140 participants). Inpatients treated with chest physiotherapy or 3 hypertonic saline both had significantly lower clinical scores at 1–3 days (1 trial; 87 participants, and 3 trials; 183 participants).
Objectives: This updated overview of reviews aims to synthesize evidence from the Cochrane Database of Systematic Reviews (CDSR) on the effectiveness and safety of 11 pharmacologic and non-pharmacologic treatments to improve bronchiolitis symptoms in outpatient, inpatient and intensive care populations.
For inpatients, nebulized epinephrine versus bronchodilator and 3 hypertonic saline versus 0.9 saline each decreased length of stay: epinephrine decreased length of stay by seven hours (4 trials; 261 participants), and 3 hypertonic saline decreased length of stay by 28 hours (4 trials; 282 participants). Outpatients treated with epinephrine or epinephrine and glucocorticoid combined both had significantly lower clinical scores at 60 minutes (4 trials; 900 participants, and 1 trial; 399 participants).
Authors’ Conclusions: For outpatients with bronchiolitis, nebulized epinephrine can be effective in avoiding hospitalization. Systemic glucocorticoids such as dexamethasone cannot be recommended as a routine therapy given the current level of evidence and potential for adverse events. For inpatients, regular nebulized hypertonic saline (3) driven using oxygen may reduce the length of hospital stay. Chest physiotherapy, nebulized epinephrine and systemic and inhaled glucocorticoids cannot be recommended for inpatients given the weak level of evidence. For the sickest of patients in the intensive care unit, intravenous immunoglobulin, heliumoxygen mixtures (heliox) and extrathoracic pressure cannot be recommended due to lack of available evidence and/or methodological flaws of reviews.
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