International Journal of Pediatrics Table 2: Evidence-based treatment options for bronchiolitis. Outpatient Nebulized Epinephrine Source: Bialy et al. [32] and Levin et al. [33]. Inpatient Nebulized Hypertonic Saline (3%) Intensive Care Unit No speciﬁc recommendations Consider empiric antibiotics for infants with respiratory failure 3 Not eﬀective Bronchodilators Glucocorticoids In a study of otherwise healthy 69 children hospitalized with bronchiolitis in Italy, none of whom required admission to the intensive care unit or treatment with bronchodilators, sinoatrial blocks were signiﬁcantly more likely to occur in RSV-positive patients than in RSV-negative patients. Fortu- nately, these sinoatrial blocks were always asymptomatic and 24-hour Holter ECG monitoring demonstrated complete regression of the sinoatrial blocks at 28 ± 3 days. This suggests that direct cardiac involvement can occur from RSV infection rather than secondary to lung alterations alone [30]. A study of 34 mechanically ventilated children with RSV bronchiolitis who did not have CHD reported that 20% had reduced right ventricular function and cardiac troponins were elevated in 41%. However, in this same study, there was no evidence of left ventricular dysfunction nor was there any relationship to elevations in myocardial or hepatic levels of troponin or transaminases, respectively, making it diﬃcult to speciﬁcally attribute RSV as the cause of cardiac ﬁndings [31]. 2.4. Treatment of Bronchiolitis. Historically the treatment of bronchiolitis has been supportive. Maintaining adequate oxygen saturation and preventing dehydration has been the mainstay of treatment for several decades. An overview of bronchiolitis treatment in various clinical settings can be found in Table 2. In outpatients with bronchiolitis, nebulized epinephrine reduced the likelihood of hospitalization and improved clinical severity scores at 60 and 120 minutes after treatment when compared to placebo. In the inpatient setting, the only intervention that has been shown to lead to clinically meaningful outcomes such as a reduction in length of stay was nebulized hypertonic saline (3%). Chest physiotherapy demonstrates some improvement in clinical score at 1–3 days but the evidence of beneﬁt is weak. Although there is not a recommended strategy for patients in an ICU setting, surfactant and immunoglobulin therapies along with standardized ventilation protocols may hold promise in the future [32]. It should be emphasized that the successful treatment options presented in Table 2 have excluded children with CHD, so caution is warranted when attempting to form more generalized conclusions regarding the eﬀectiveness of these therapeutic options. Rates of bacterial pneumonia can be 20% or higher in patients with RSV infection and respiratory failure. Therefore it appears reasonable to start empiric antibiotics for 24 to 48 hours pending culture results in this group of patients [33]. A common clinical scenario that health care providers face is how to evaluate and treat the presence of fever in infants with bronchiolitis, particularly those under the age of three months. Fortunately, the overall frequency of serious bacterial infections (SBIs) in a study of over 4000 patients <2 years of old, hospitalized with bronchiolitis, was low. The overall frequency of SBIs was 1.0% in RSV-positive patients and 0.7% in RSV-negative patients (not statistically signiﬁcant). The most common SBI was a urinary tract in- fection, and there were no cases of positive cerebrospinal ﬂuid cultures [7]. Currently, respiratory support interventions for patients with severe bronchiolitis are being examined to reduce the need for mechanical ventilation but the choice of modalities is still largely based on clinical judgment and larger clinical trials are needed to deﬁne optimal strategies. In this regard, a recent retrospective study that examined heated, humidiﬁed, high-ﬂow nasal cannula (HFNC) demonstrated a signiﬁcant 68% reduction in the need for intubation in infants with bronchiolitis. HFNC allows the delivery of high inspired gas ﬂows, with or without an increased oxygen concentration, and provides a variable degree of continuous positive airway pressure that leads to decreased work of breathing. However, prospective randomized trials are needed [34]. 3. Immunoprophylaxis 3.1. Palivizumab. Palivizumab is a humanized murine mon- oclonal antibody directed against the fusion protein of RSV that in preclinical trials was able to neutralize both subtypes of RSV strains and was 50- to 100-fold more potent than respiratory syncytial virus immune globulin administered intravenously (RSV-IGIV) [35]. The use of RSV-IVIG, containing high levels of RSV-neutralizing anti- body, became contraindicated in the use of children with cyanotic CHD due to an increased frequency of cyanotic events. This increase in frequency of cyanotic episodes may relate to increased blood viscosity, secondary to reactive polycythemia, commonly seen in patients with a right-to-left cardiac shunt [36]. In a multinational, randomized, double-blind, placebo- controlled trial, children ≤24 months of age who had hemodynamically signiﬁcant congenital heart disease were administered either 15 mg/kg of palivizumab or an iden- tically appearing placebo every 30 days for a total of 5 doses during four consecutive RSV seasons (1998–2002). Pa- livizumab recipients experienced a signiﬁcant 45% rela- tive reduction in RSV hospitalizations when compared to placebo (9.7% hospitalization rate in placebo group vs. 5.3% in palivizumab group). Palivizumab recipients also spent signiﬁcantly less days in the hospital and had less days requiring oxygen supplementation. There was also a trend for decreased need of intensive care and mechanical ventilation. The mortality rate was 3.3% in palivizumab