Viral bronchiolitis (Part two)
Viral bronchiolitis: Clinical Features, Diagnosis, Management of acute illness.
The clinical syndrome of bronchiolitis typically begins with an upper respiratory tract infection manifest by fever and coryza. After 2–3 days, the lower respiratory tract involvement becomes obvious with worsening cough and shortness of breath. Apnoea is a frequent complication and may occur in up to 20% of cases, particularly in premature infants. Clinical examination findings include increased respiratory effort, wheezing and fine crackles on auscultation, and dehydration.
Most infants show signs of improvement within 3–4 days after the onset of lower respiratory tract disease.
Otitis media is frequently seen in association with RSV bronchiolitis. However, serious bacterial infection rarely accompanies RSV bronchiolitis. Routine antibiotic treatment does not improve the recovery of infants with RSV lower respiratory infection. The chest x-ray, if performed, typically shows hyperinflation. Consolidation is found in up to 25% of cases but generally, the severity of the infant’s illness is not mirrored by radiological changes.
Diagnosis can be confirmed by finding evidence of RSV infection from nasopharyngeal aspirates. Rapid diagnosis is available using immunofluorescence, both direct and indirect, which has high sensitivity and specificity, and enzyme-linked immunosorbent assay (ELISA) which has slightly less sensitivity. Cell culture generally takes too long (4–5 days) to be of use clinically. Serological diagnosis is not appropriate in infants as there may be a poor serological response and seroconversion may take weeks.
Management of acute illness
The diagnosis is usually a clinical one and investigations are not generally needed to confirm the diagnosis. Confirmation of RSV infection can be made by isolation of the virus from nasopharyngeal aspirates by immunofluorescence or ELISA. This is particularly useful if infants are to be nursed in the same room or by the same nurse, as RSV is a major nosocomial pathogen in pediatric wards. It is not necessary to perform a chest x-ray routinely on infants as it does not predict severity and does not alter management. Infants requiring assisted ventilation by continuous positive airways pressure (CPAP) or full ventilation may benefit from a chest x-ray. Blood tests are not usually helpful in the management and should not be routinely performed.
Treatment is largely supportive, paying attention to hydration and maintaining satisfactory oxygenation (Table 2).
The oxygen saturation level should at least be kept above 92%. Some units elect to maintain the oxygen saturation above 95%. There are no systematic reviews (or) randomized controlled trials on the use of oxygen, but extrapolated evidence from case-control studies shows hypoxemia as a risk factor for near-fatal asthma. Antibiotics As mentioned above, there is no place for the routine use of antibiotics in infants with bronchiolitis. They do not alter the course of the disease. Although the risk of serious bacterial infection is low in infants with RSV bronchiolitis, many clinicians would elect to add antibiotics to the regimen of infants requiring assisted ventilation.
Bronchodilators are used frequently in the management of bronchiolitis. In the UK, ipratropium bromide is used frequently, while in the USA salbutamol (albuterol) is used more often. Systematic reviews have shown there is only modest benefit from bronchodilators in short-term clinical scores. The significance of this effect is not clear, particularly as the studies in the systematic reviews used different agents and different outcome measures. Many units elect to give a trial of a bronchodilator and, if there is no positive response, it is discontinued. As some of these first-time wheezing infants may have asthma, this does not seem an unreasonable approach.
Adrenaline (epinephrine) has both alpha and beta-adrenergic properties and the alpha-adrenergic effect, via vasoconstriction of the pulmonary vessels and reduction in oedema, has been considered a possible useful action in the treatment of bronchiolitis. One study found that adrenaline substantially improved respiratory system resistance but not oxygenation or ventilation indices. Most of the studies of adrenaline show it has a good safety profile, although there is one report of non-fatal myocardial infarction in a child who presented with croup and was given repeated doses of nebulised adrenaline. In studies where a benefit has been seen in bronchiolitis (in the outpatient setting), only limited doses of adrenaline have been given. A systematic review on the use of nebulized adrenaline in bronchiolitis has shown some benefits in the outpatient setting (such as clinical score improvements and improved oxygenation) but little convincing evidence for its use in the inpatient setting. The authors concluded that large multicentre randomised controlled trials are necessary to address fully the usefulness of adrenaline in the treatment of bronchiolitis. Like bronchodilators, a trial may be appropriate to assess the individual infant’s response.
Steroids (inhaled and oral) have been used in the acute management of bronchiolitis in an attempt to reduce both acute symptoms and post-bronchiolitic wheeze (see below). Despite studies with varying results, a systematic review has failed to show any benefit from steroids in the acute management of bronchiolitis. Studies, where positive effects have been shown, have often failed to exclude infants with recurrent wheeze who may have asthma and so respond to steroids. There is no evidence to support the use of steroids in the acute management of bronchiolitis.
There is no compelling evidence on the effectiveness of chest physiotherapy in bronchiolitis and a Cochrane review is currently underway. Minimal handling is thought by many to be important in the acute management of bronchiolitis and without any evidence to support the use of chest physiotherapy, it should not be part of routine management.
Ribavirin is a purine nucleoside analogue. It is believed to interfere with the normal function of viral nucleic acid. Ribavirin has activity towards RSV, influenza, and hepatitis C. Systematic reviews have failed to show any effect from the use of ribavirin in the acute setting, although there is a suggestion of benefit (although not significant) in those with severe disease requiring intensive care. Although early guidelines suggested that it be administered as an aerosol for 12–18 hours daily, it has been used in shorter bursts (two hours three times per day) in the same dose of 6 g/day. It is given for 3–5 days. The short burst regimen cannot be used in ventilated patients as it causes increased deposition in ventilator circuits. Ribavirin is expensive and difficult to administer and, as a result, its use is generally restricted to those patients who are at risk of severe infection. Ribavirin is potentially toxic not only to the patient but also to those in close contact with the patient. It has been shown to be teratogenic in animal studies and pregnant women should avoid contact with patients receiving the drug. The difficulty of administration along with the potential toxicity and the limited evidence supporting its use means ribavirin is not widely used as a treatment for acute bronchiolitis.
RSV immunoglobulin (RSV Ig) is derived from adult donors with high anti-RSV titers. It has a low risk of blood-borne viral transmission because of the sterilization process it goes through. RSV Ig has been used for the acute treatment of bronchiolitis and for prevention (see below). There is currently no evidence to support the use of RSV Ig in the acute management of bronchiolitis. A systematic review is planned.
Palivizumab is a humanized monoclonal antibody produced with recombinant DNA technology and has similar activity against both strains (A and B) of RSV. There is no evidence that palivizumab is effective in the acute treatment of bronchiolitis. It has been used to prevent RSV bronchiolitis (see below). Assisted ventilation RSV bronchiolitis can cause severe respiratory compromise and occasionally ventilatory support is necessary. Many units have the facility for continuous positive airway pressure (CPAP) in a high dependency area and there is good supportive evidence for this practice. Some infants require full ventilation in an intensive care setting.
Other treatments including interferon, vitamin A, and recombinant human deoxyribosenuclease 1 (rhDNase1) have been tried but have shown no benefit. Chinese herbs, surfactants, and Heliox possibly warrant further investigation. On current evidence, surfactant and Heliox (helium and oxygen) should be reserved for use in patients in paediatric intensive care units.