Oxygen
Oxygen should be administered in hypoxic infants with bronchiolitis, and administered via nasal cannulae or a face mask [
1]. However, there is no consensus on what level of oxygen saturation (SpO
2) oxygen support should be aiming at, and no randomized controlled trials have compared alternative oxygen supplementation regimes [
1,
40]. In the UK, oxygen is commonly given to achieve a SpO
2 of 92-95%, while the AAP recommends a limit of SpO2 of 90% in otherwise healthy children [
1‐
3,
7,
39]. Observational studies, however, indicate that a goal of 90%, as compared to 94%, has the potential to significantly reduce length of hospital stay [
41,
42], and the AAP guidelines recommend a reduced level of monitoring as the infants improve [
3].
Fluid and nutrition
Maintaining hydration is an important part of the care of infants with bronchiolitis. The respiratory distress due to increased work of breathing may cause inadequate feeding and eventually lead to poor hydration [
1]. Further, tachypnoe and fever increases fluid loss, potentially worsening the dehydration [
43,
44]. Oral feeding may be sustained in milder cases, if needed by small volume frequent feed, and breastfeeding should be encouraged. However, a substantial part of infants hospitalized for bronchiolitis will be in need of fluid supplementation, either as intravenous (IV) fluid or with enteral feeding by gastric tube (GT) [
1,
2,
44]. Traditionally, IV fluid has been given in many countries, and is also recommended in the present AAP guidelines [
3]. The advantage of IV fluids could be a decreased risk of aspiration and no interference with breathing [
45,
46], but with the disadvantage of possibly creating a catabolic state due to low calorie intake, and bearing a higher risk of fluid overload and electrolyte imbalance [
43,
44,
46]. Through GT feeding, infants may achieve a better nutritional status and nitrogen balance, which may be beneficial for recovery, and may be a route for giving expressed breast milk [
44,
47]. Feeding by GT may be given as boluses, or continuously in case of major respiratory distress [
1].
Currently there is not sufficient evidence for or against the use of GT feeding in infants with bronchiolitis [
46], and in a recent large study from Australia no differences in major outcomes were found between the two methods [
48]. However, feeding by GT has been increasingly adopted, and used as routine in some countries [
41,
49,
50], including the recent guidelines of the Norwegian Paediatric society [
51]. In a large Scottish study of bronchiolitis, no children received IV fluids, and no complications related to feeding by GT were reported [
41]. Recently, a minor randomized pilot study comparing IV fluid and feeding of GT showed no difference regarding the duration of oxygen supplementation or length of stay between the two methods [
43].
Few studies have addressed the appropriate amount of fluid to be given during replacement in bronchiolitis. Guidelines recommend that infants should receive enough fluid to restore fluid loss and avoid dehydration, and the amount should not exceed 100% of daily fluid requirements, normally set to 100 ml/kg for infants < 10 kg [
3]. However, fluid retention due to inappropriate secretion of antidiuretic hormone has been reported in bronchiolitis, and clinicians should be aware of the possibility of overhydration [
1,
52,
53]. Consequently, 70-80% of the daily requirements may be recommended, especially in those with severe disease [
1,
3,
44]. In these children, close monitoring of weight, serum and urine-osmolality and serum electrolytes may guide treatment [
1]. Probably, possible overhydration will be a less problem during enteral feeding, permitting the body to absorb the needed amount of fluid and electrolytes.
Inhaled saline
Inhaled normal saline (0.9%) is commonly used for children with bronchiolitis to increase clearing of mucous, and is included as placebo in many studies evaluating the effect of bronchodilators or hypertonic saline. However, we are not aware of any randomised study comparing normal saline with no treatment, and normal saline is not suggested in current guidelines and reviews [
1‐
3,
6,
39]. Consequently, no recommendations can be given.
Inhaled hypertonic saline has, in patients with various diseases, shown to increase mucociliary clearance possibly through induction of an osmotic flow of water to the mucus layer and by breaking ionic bonds within the mucus gel [
54]. Recent metaanalyses including more than 1000 infants with mild to moderate bronchiolitis, concluded that the use of hypertonic saline (3-5%) may reduce the length of hospital stay and the rate of hospitalization [
55,
56]. However, due to the possible side effect of bronchospasm, all but few patients received a combination with a bronchodilator. The optimal delivery interval, concentration and delivery device remain unclear. The short term effect was conflicting, as four trials showed no such effect [
55]. In a recent study, 7% hypertonic saline with epinephrine did not have any effect on the clinical severity score [
57].
A recommendation of hypertonic saline inhalations based on the current evidence must include a bronchodilator. As recent evidence strongly supports the “minimal handling” approach to infants with bronchiolitis [
23], we do not support such a recommendation at this time. Several trials with hypertonic saline without bronchodilators are ongoing, from which results may adjust guidelines [
1].
Inhalations with bronchodilators
In addition to bronchodilation, inhalation with adrenaline may reduce mucosal swelling, which has led to frequent use in infants with bronchiolitis. However, a clinically important, significant effect has been documented for neither adrenaline nor beta-2-agonists. Studies on short-term effects show conflicting results. A recent Cochrane review concludes that inhaled (racemic) adrenaline does not improve important clinical outcomes such as length of hospital stay or the use of supportive care in moderate to severe bronchiolitis inpatients [
58]. This is supported by a recent large Norwegian randomised controlled trial (RCT) of 404 infants [
23]. In this study, treatment “as needed” rather than on a fixed schedule resulted in less inhalations (12 vs. 17 per day), shorter hospital stay (47.6 vs. 61.3 hours), less use of supplemental oxygen (38.3 vs. 48.7%) and less ventilatory support (4.0 vs. 10.8%). The effect was predominantly seen in children <3 months (25 hours reduced hospital stay), which also tended to have a negative effect of adrenaline compared to saline, supporting a conservative approach particularly in this age group. Adrenaline is therefore not recommended as a standard treatment in infants with bronchiolitis, but a trial might be performed in children >3 months, with critical evaluation of effect with respect to continuation of administration [
23]. Beta-2-agonists are not recommended for infants with bronchiolitis [
59,
60].
Additional medication
Antibiotics is commonly used in children with lower respiratory tract infections, but a Cochrane review including 543 infants concludes that there is no evidence for the use of antibiotics in general [
64]. However, antibiotics may more frequently be warranted due to concurrent bacterial infections in infants with severe disease, especially those needing mechanical ventilation [
65]. There is no role for antiviral therapy in bronchiolitis [
66].
Surfactant therapy has been suggested for critically ill patients on mechanical ventilation. So far, this has been evaluated in only three small studies, and a recent Cochrane review concluded that there is insufficient evidence for such treatment [
67]. The use of recombinant human deoxyribonuclease has not been efficacious on any of the outcome variables in children with bronchiolitis [
68].
Non-invasive and invasive ventilation
Continuous positive airway pressure (CPAP) with a nasal tube or a nasal mask has been widely used in children with moderate or severe bronchiolitis. CPAP may act by recruiting collapsed airways and the corresponding alveoli, giving a reduction in mean airway resistance. This further increases the emptying of the lungs during expiration, resulting in a decreased hyperinflation and work of breathing, and improved gas exchange [
69,
70].
Contrasting the widely use, the documentation for the use of CPAP in bronchiolitis is sparse. A recent systematic review concluded that the evidence supporting the use of CPAP to reduce PCO
2 and respiratory distress is of low quality, and it has not been shown that the use of CPAP reduces the need for invasive ventilation [
69]. Only two small RCTs have been performed [
71,
72], the other studies have a before-after design [
73‐
77]. However, these studies have found that the use of CPAP in bronchiolitis is safe, and on average reduces the capillary PCO
2 from before to shortly after CPAP is initiated with 0.8 to 1.3 kPa [
69].
The pressure used during ventilation with CPAP is commonly set to 4–8 cm H
2O, and a pressure of 5 cm H
2O has been efficient in reducing PCO
2. Recently, a prospective study suggested that a nasal CPAP level of 7 cm H
2O was most efficient in reducing respiratory distress and improving the breathing pattern [
78].
Heliox is a mixture of helium and oxygen and a low-density gas. It may have a beneficial role in bronchiolitis by transforming turbulent into laminar gas flow and thereby improving oxygenation and the washout of CO
2[
79]. The combination of heliox and CPAP (CPAP-He) has been evaluated in three studies. All the studies included few children, one quasi RCT and two before-after studies [
69,
80‐
82]. All three studies showed a significantly decrease in transcutaneous or arterial PCO
2 and respiratory distress. However, as no blinded RCT has been performed, it must be concluded that more evidence is needed before CPAP-He can be included in guidelines [
69]. Heliox therapy without the use of a tight CPAP or combined with a nasal cannulae has been shown to be ineffective [
83].
Though no uniform criteria have been published, common criteria for which children should be treated with CPAP are respiratory distress, high oxygen requirement or increasing pCO
2 and apnoeas [
1]. In a recent study, the strongest predictors for CPAP treatment were oxygen requirement, low oxygen saturation, younger age and higher respiratory rate [
84].
The use of heated humidified high-flow nasal cannulae (HFNC) has increasingly been introduced as an alternative to nasal CPAP [
85‐
91], also in a general paediatric ward [
92]. The method is currently used in neonatal medicine [
93], and may generally act by increasing the pharyngeal pressure, leading to a reduction in respiratory efforts and improving respiratory distress [
94]. Based on the current literature, a recent review concludes that HFNC may be feasible in infants with bronchiolitis and may decrease the need for intubation [
87,
90]. HFNC may be better tolerated than nasal CPAP [
86,
89,
95], and larger paediatric units have replaced CPAP with HFNC as the first-line non-ventilatory support in bronchiolitis [
86]. However, no randomized trial has yet evaluated the effect in bronchiolitis patients, and the most recent study concludes that there is insufficient evidence to determine the effectiveness of HFNC in infants with bronchiolitis [
96]. Serious air leak syndrome has been shown in some cases of children treated with HFNC [
97].
The safety of HFNC and CPAP may be arguments for the early introduction of non-ventilatory support in children with moderate bronchiolitis [
69]. However, mechanical ventilation may still be necessary in infants with insufficient support by nasal CPAP or HFNC. Risk factors include prematurity, low birth weight and bronchopulmonary dysplasia, and further those with apnoe, low oxygen saturation, poor oral intake and severe retractions on admission [
98,
99].
There is no consensus on which ventilator technique is the best for children with bronchiolitis [
70,
100]. Both volume and pressure cycled ventilation has been used, with a large variation in ventilator rates (10–60 beats per minute), maximum pressure (20–50 cm H
2O) and tidal volume (6–20 ml/kg) [
70]. The use of PEEP is also varying, from 0 to 15 cm H
2O. The use of high frequency oscillation has been successful in some case reports [
101]. However, it is suggested that infants with hyperinflation may benefit from slower rates and longer expiratory times [
70].
For those very few not controlled on mechanical ventilation (in most cases associated with severe bronchopulmonary dysplasia), extracorporeal membrane oxygenation has been shown to have some benefit [
70,
98].