Current Paediatrics (1996) 6, 252 256 1996 Pearson Professional Ltd

Serial: Bronehiolitis

Management of acute bronchiolitis

M . S. C. W e b b , L. J. R e y n o l d s

The onset of winter heralds the annual influx of babies with acute bronchiolitis requiring admission to paediatric wards all over the country, resulting in the familiar severe pressure on cots and consequent high stress levels in medical and nursing staff. In our district general hospital, with a birth rate of 4000 per year and serving a child population of 70 000, we admit about 150 such babies each winter, the vast majority of whom (90-96%) are respiratory syncytial virus (RSV)-positive. Bronchiolitis can cause significant morbidity in previously healthy infants and is potentially lethal, especially to babies with severe cardiorespiratory disease or immunological compromise. Despite a global effort and enormous resources devoted to research into both the RSV itself and various treatments for bronchiolitis, we are little further advanced in our management of the condition than in 1963 when Reynolds and Cook made the much cited observation that 'oxygen is vitally important in bronchiolitis and there is little convincing evidence that any other therapy is consistently or even occasionally useful'? There are, however, a number of treatments that are promoted; with more or less evidence to justify their use, and it is on these treatments that this review will concentrate.

bronchiolitis. In the U K and Australia, and for the purposes of this article, bronchiolitis is defined clinically as an infant, usually in the first few months of life, who presents with a 2-3 day upper respiratory prodrome leading to increasing respiratory difficulty manifested by tachypnoea associated with chest hyperinflation, widespread fine crepitations and often, but not always, audible wheeze and scattered rhonchi on auscultation? The confusion arises because in the USA and in some European countries, bronchiolitis includes older children with recurrent attacks of wheezing, or what we would almost certainly call asthma, thereby confounding the interpretation of trials of different treatments.

AETIOLOGY AND PATHOPHYSIOLOGY Acute bronchiolitis is caused by infection with RSV in over 90% of cases in our experience; viruses such as parainfluenza, influenza and adenovirus can cause an indistinguishable clinical picture. Co-infection with other organisms such as Chlamydia trachomatis and Mycoplasma pneumoniae can occur and should be sought and treated in the atypical or severe case. Secondary bacterial infection is rare? The virus invades the bronchiolar epithelium, resulting in destruction of cilia and necrosis of epithelial cells, leading to intraluminal plugging with secretions and cellular debris. Airway obstruction, further exacerbated by submucosal oedema, leads to widespread atelectasis and hyperinflation. This produces a ventilation/perfusion mismatch which, with the simultaneous increase in work of breathing due to a rise in respiratory resistance and fall in dynamic compliance, causes increasing hypoxia and hypercapnia. These changes will occur more rapidly and to a greater degree in any infant with pre-existing cardiorespiratory disease.

DEFINITION Much of the controversy surrounding aspects of management of this common condition arises out of the range of clinical entities ascribed the term

Michael S. C. Webb FRCE Consultant Paediatrician, Lucy J. Reynolds, MRCP, Registrar, Department of Paediatrics, Gloucestershire Royal Hospital, Great Western Road, Gloucester GL1 3NN. Correspondence and requests for offprints to MSCW.

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Management of acute bronchiolitis CLINICAL PRESENTATION AND DIAGNOSIS Typically, the illness begins with 1-3 days of coryzal symptoms, progressing to cough and tachypnoea with or without wheeze. It is often the onset of difficulty in feeding, associated with increasing respiratory distress, that precipitates hospital admission and by that stage the baby appears to the parents to be quite seriously ill. The child may well have been seen by the general practitioner (GP) once or twice prior to admission and a diagnosis of upper respiratory tract infection (URTI) made. It is important that injudicious comments by hospital staff implying that the diagnosis of bronchiolitis is obvious, thereby undermining the GP's credibility, should not be made. On admission, the child is usually not toxic but has fast shallow breathing, a barrel-shaped chest with subcostal retractions and sometimes an audible wheeze. Auscultation reveals widespread fine crepitations, often but not always with rhonchi. Cyanosis may be present. The liver is often displaced downwards by the hyperinflation. Less common presentations, preceding any respiratory symptoms or signs, can be hypothermia, a septic shock appearance or apnoea (especially inthe very young or in ex-premature babies)? Diagnosis is based primarily on the clinical picture and is straightforward in a typical case during the RSV season. However, it is precisely during that period, when droves of babies are being admitted, that diagnostic complacency can set in. Vigilance is required to pick up the occasional baby whose presentation or course is unusual and who may therefore have another underlying condition or a different primary diagnosis. In the majority of cases, the only justifiable routine investigation is to obtain nasopharyngeal secretions to detect RSV or other viral antigen on exfoliated respiratory epithelial cells by direct immunofluorescence. Traditionally this has been done by taking a nasopharyngeal aspirate (NPA). It has recently been suggested that nasopharyngeal lavage, using 2 ml of phosphate buffered saline into each nostril, has as good a positive and negative predictive value as NPA but, more importantly, is better tolerated by the infant. 5 There is no statistical correlation between chest X-ray changes and clinical severity6 and therefore chest X-ray is only indicated where the diagnosis is in doubt or where underlying disease is suspected. Similarly, routine full blood count or biochemistry seldom alters management but dehydration or inappropriate antidiuretic hormone (ADH) secretion can occur and should be assessed biochemically if clinically indicated.

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main aims of management must be to anticipate and prevent these. The presence of crackles, a respiratory rate greater than 70 breaths/min, cyanosis or an ill or toxic-looking child all correlate with more severe disease. 7,8Any of these may therefore aid the GP in deciding to admit the child. However, once the child is ill enough to require admission, there is a very poor correlation between clinical signs (other than overt cyanosis) and hypoxia and therefore all children should undergo oxygen saturation (Sao2) monitoring by pulse oximetry. Saturation monitoring is superficially a simple procedure but all units should be aware of the pitfalls. Medical and nursing staff should know of the variability of baseline oxygenation and brief respiratory pauses with desaturation that occur in normal healthy term and ex-premature infants2 ,~ Inappropriate sensor application which allows light to bypass the tissue bed can lead to significant underreading of oxygen saturation. 11 Pulse oximetry is unreliable if Sao 2 is below 80%, or if there is significant anaemia, hypotension or hypothermia. Infants at risk of severe disease are listed in Table 1. These infants should be admitted to hospital more readily, they should be monitored more intensively, including apnoea monitoring, and there should be a lower threshold for admitting them to the intensive care unit.

TREATMENT The management of babies with acute bronchiolitis is almost entirely that of good nursing care, with the minimum disturbance and handling that is compatible with necessary monitoring and fluid administration. Babies' respiration often appears less distressed in the prone position, although some parents find this alarming in view of current advice about supine sleeping in relation to reduced risk of sudden infant death. A range of specific treatments must be considered for each individual case (Table 2). Oxygen Oxygen is the single most important and least controversial treatment. Warmed and humidified oxygen

Table 1 Infants at risk of severe disease

ASSESSMENT AND MONITORING OF SEVERITY Hypoxia and respiratory failure are the most serious complications of acute bronchiolitis and one of the

Age less than 6 weeks Premature birth Bronchopulmonary dysplasia or chronic lung disease of prematurity Other pre-existing lung disease, e.g. cystic fibrosis Congenital heart disease, especially associated with pulmonary hypertension or cyanosis Immunocompromised

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Current Paediatrics North American researchers, often by including older children with a history of recurrent chestiness and a low percentage RSV-positive, demonstrate a beneficial outcome from the use of bronchodilators, notably ~-agonists and adrenaline. Clinical trials claiming benefit have studied a range of outcome measures, such as various lung function parameters and clinical scoring systems, but have not shown a reduction in hospital stay. British and Australian authors, on the other hand, consistently fail to confirm these positive findings on younger babies with acute viral bronchiolitis, the vast majority of whom have RSV infection. Interested readers wishing to explore this dichotomy further are referred to two brief commentaries and their references, I3,~4both of which advocate no role for bronchodilators. The very few more recently published trials can be criticized for the same design flaws and do not suggest that this view should be altered. In summary, therefore, the routine use of bronchodilators is not indicated in acute viral bronchiolitis. In clinical practice, however, it is not always quite so clear-cut. In the older child, perhaps over 6 months, if there is a history of recurrent chestiness or if wheeze and rhonchi predominate over crepitations, and even if the child is known to be RSV-positive, it would seem reasonable to give a trial of bronchodilator. This could be continued if there appeared to be clinically relevant benefit. Ipratropium bromide, or possibly a ~3-agonist, should be offered by spacer and mask in preference to nebulizer because of the risk of short-term deterioration with the latter, and a careful watch kept on respiration and oxygen saturation. If a nebulizer must be used, it should be driven by oxygen to minimize any increase in ventilation/perfusion mismatch. Babies with bronchopulmonary dysplasia may also benefit from a similar trial of bronchodilator.
Ribavirin

Table 2 Treatmentof acute bronchiolitis

Provenbenefit/routinemanagement Oxygen Maintenancefluids Unprovenbenefit/selectedpatients only Bronchodilators Ribavirin Complicatedcases Assistedventilation Antibiotics No role at all Corticosteroids Chest physiotherapy

(30-40%) delivered via a headbox is well-tolerated and will usually correct hypoxia and thereby substantially relieve agitation and distress in the majority of infants. S a o 2 levels of 93-95% should be maintained in the acute phase. A higher concentration of inspired oxygen may be required to achieve these levels, but although this does not of itself increase the risk of hypercapnia, increasing oxygen requirements may be a sign of impending respiratory failure and arterial gases should be monitored.
Fluids

Babies who are feeding adequately by mouth may continue to do so, with appropriate volumes for age. However, many babies are admitted at the stage when feeding is becoming a problem. This raises the question of whether to continue with frequent small-volume feeds by mouth, at the risk of the baby tiring or aspirating, or to feed nasogastrically or give intravenous fluids. Theoretically, a nasogastric tube which partially or totally blocks one nostril will increase the work of breathing in an already compromised individual and some would argue that this should never be done in babies with bronchiolitis?2 In practice, however, provided that the initial insertion of the tube does not cause undue distress, a considerable majority of babies will tolerate nasogastric feeds perfectly well, with small-volume boluses if necessary. Intravenous fluids should be given to the sickest infants with severe respiratory distress and to those who do not tolerate nasogastric feeds. Dextrose and electrolytes usually suffice in this relatively short-lived condition. A balance needs to be struck between the risk of dehydration in a tachypnoeic infant and the possibility of inappropriate A D H secretion which can occur, particularly in seriously ill infants. It may be advisable in these to restrict fluids to 70-80% of maintenance and to monitor creatinine and electrolytes.
Bronchodilators

It is over the role of bronchodilators that the differing definitions of the term bronchiolitis have created most confusion.

gibavirin is a broad-spectrum antiviral drug with in vitro inhibitory activity against replication of RSV, influenza, parainfluenza, adenovirus, measles and some other more exotic viruses. It is licensed for use against RSV infection in humans. Ribavirin is administered as aerosolized particles small enough to reach the lower respiratory tract. The drug is delivered through a small-particle aerosol generator (SPAG) into a headbox, usually at a dose of 6 g in 300 ml water over 12-18 h per day. The drug can be administered through a ventilator but tends to crystallize out in the circuits, particularly the expiratory line, thus requiring special filters to be inserted. It is expensive, costing 250 per 6-g vial. There are concerns about safety, notably in relation to possible teratogenic side-effects in pregnant eaters, leading some authors to suggest fairly draconian protective measures for staff. The major controversy, however, relates to efficacy. Early studies in the 1980s suggested significant benefit

Management of acute bronchiolitis in moderate or severe RSV infection in a wide range of patients. This led the American Academy of Pediatrics (AAP), in 1993, to recommend what they called a selective policy towards prescribing ribavirin. The criteria were, however, fairly broad and the drug became widely used across the USA. No specific or authoritative guidelines were issued in this country at that time, but prescribers were probably more circumspect. More recent studies have attempted to address some of the original papers' design flaws and have seriously challenged whether ribavirin has any part to play in the treatment of RSV infection at all. They have shown that both in previously healthy and in high-risk infants (with the possible exception of immunocompromised infants), ribavirin does not reduce lengths of hospital stay, days in the intensive care unit or days on a ventilator and in some instances it actually increases these outcome measures. Mortality from bronchiolitis used to be quoted at 1-2% of all admissions and 30M0% for high-risk babies. More recent estimates suggest much lower figures of well under 1% for previously healthy infants and 3 4 % in immunocompetent high-risk patients, though significantly higher rates are reported for immunocompromised patients. The AAP and Committee on Infectious Diseases have therefore reviewed and revised their recommendations? 5 The wording has been changed from the previous 'should be used' to 'may be considered', but their recommendations for those infants who should be 'considered' for treatment are still wideranging. These include all infants listed in Table 1, plus any severely ill infant and any infant with an underlying condition such as multiple congenital abnormalities or certain neurological or metabolic diseases. Despite the AAP stopping well short of recommending that ribavirin should no longer be used (which they say they considered), there seems to us to be very little justification for using this expensive drug, which is complicated to administer. A probable exception would be in the immunocompromised patient with a high mortality risk. We are aware that a number of paediatric intensive care units around the country are no longer using ribavirin routinely, even in the sickest infants. There is an urgent need for multicentre trials to assess possible efficacy in highly selected high-risk infants.
Assisted ventilation

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no absolute criteria for defining respiratory failure; rather it is a combination of arterial blood-gas measurements and physical signs, especially of altered conscious level or exhaustion, that will inform the decision. Babies with carbon dioxide tension levels as high as 12 kPa can be appropriately managed without ventilatory support. Any baby requiring, or likely to require, assisted ventilation should be transferred to a paediatric intensive care unit. Continuous positive airways pressure through nasal prongs may be tolerated and effective in some babies and is worth considering relatively early in babies with bronchopulmonary dysplasia with their unstable airways. Ventilation is safe in skilled hands? 6 Using time-cycled, pressure-limited ventilators, highish peak inspiratory pressures (up to 40 cm H20 ) and slow rates (15-25) with I:E ratios of 1:2 may be required. Permissive hypercapnia, i.e. achieving a satisfactory pH (>7.25) irrespective of carbon dioxide level, is now an accepted aim. Babies should be weaned off the ventilator as soon as possible. Extracorporeal membrane oxygenation is now a realistic option for those babies in whom conventional ventilation is proving unsuccessful. 17
Corticosteroids

There is no published evidence to suggest that steroids, inhaled or systemic, affect either the course of the acute illness or the long-term outcome.
Antibiotics

Secondary bacterial infection is rare and therefore antibiotics are not routinely indicated. However, any baby who presents with a septic shock appearance, even if there are specific pointers towards the diagnosis of RSV infection, should be covered with broadspectrum antibiotics until bacterial infection is excluded by appropriate cultures. It is also difficult not to offer antibiotics to severely ill babies who have patchy infiltrates on chest X-ray, though these changes can be entirely consistent with isolated RSV infection.
Miscellaneous

Ventilatory support is required in a small proportion of babies admitted to a district general hospital, the majority of whom will be in the high-risk group (Table 1). In a significant number, particularly ex-premature and very young babies, the indication for ventilation is severe recurrent apnoea with desaturation. In the remainder, it is increasing respiratory failure leading to deteriorating respiratory acidosis. There are

Sedation should very seldom be necessary and may be dangerous. Correction of hypoxia and skilled nursing care, the cornerstones of management, should settle an agitated infant. Chest physiotherapy not only produces no benefit but constitutes significant handling and as such can cause acute deterioration. A study comparing a 7-day intravenous infusion of the Chinese herb Shuang Huang Lian, either alone or with antibiotics, produced a more rapid improvement and a shorter hospital stay than antibiotics alone! Given that at least there were no recorded side-effects, perhaps this remedy merits further exploration.

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REFERENCES 1. Reynolds E O R, Cook C D. The treatment of bronchiolitis. J Pediatr 1963; 63: 1205-1207. 2, Phelan P D, Olinsky A, Robertson C E Respiratory illness in children. Oxford: Blackwell Scientific Publications. 1994: p 52-93. 3. Hall C B, Powell K R, Schnabel K C, Gala C L, Pincus C H. Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection. J Pediatr 1988; 113: 266-271. 4. Njoku D B, Kleigman R M. Atypical extrapulmonary presentations of severe respiratory syneytial virus infection requiring intensive care. Clin Pediatr 1993; 32: 455460. 5. Balfour-Lynn I M, Girdhar D H, Aitken C. Diagnosing respiratory syncytial virus by nasal lavage. Arch Dis Child 1995; 72: 58-59. 6. Dawson K P, Long A, Kennedy J, Mogridge N. The chest radiograph in acute bronchiolitis. J Pediatr Child Health 1990; 26: 209-211. 7. Mulholland E K, Olinsky A, Shann F A. Clinical findings and severity of acute bronchiolitis. Lancet 1990; 335: 1259-1261. 8. Shaw K N, Bell L M, Sherman N H. Outpatient assessment of infants with bronchiolitis. Am J Dis Child 1991; 145: 151-155. 9. Stebbens V A, Poets C F, Alexander J R, Arrowsmith W A, Southall D R Oxygen saturation and breathing patterns in infancy. 1: Full term infants in the second month of life. Arch Dis Child 1991; 66: 569-573. 10. Poets C F, Stebbens V A, Alexander J R, Arrowsmith W A, Salfield S A W, Southall D R Oxygen saturation and breathing patterns in infancy. 2: Preterm infants at discharge from special care. Arch Dis Child 1991; 66: 574-578. 11. Southall D P, Samuels M. Inappropriate sensor application in pulse oximetry. Lancet 1992; 340: 481482. 12. Sporik R. Why block a small hole? The adverse effects of nasogastric tubes. Arch Dis Child 1994; 71: 393-394. 13. Archivist. Salbutamol in bronchiolitis. Arch Dis Child 1991; 66: 1183. 14. Tsai Goodman B, Chambers T L. Bronchodilators for bronchiolitis? Lancet 1993; 341: 1380. 15. American Academy of Pediatrics; Committee on Infectious Diseases. Reassessment of the indications for ribavirin therapy in respiratory syncytial virus infections. Pediatrics 1996; 97: 137-140. 16. Lebel M H, Gauthier M, Lacroix J, Rousseau E, Buithieu M. Respiratory failure and mechanical ventilation in severe bronchiolitis. Arch Dis Child 1989; 64: 1431-1437. 17. Khan J Y, Kerr S J, Tometzki A et al. Role of ECMO in the treatment of respiratory syncytial virus bronchiolitis: a collaborative report. Arch Dis Child 1995; 73: F91-F94.

PREVENTION

RSV infection is highly contagious and nosocomial spread commonly occurs. Transmission is mainly on the hands of ward staff, rather than by aerosolized droplet inhalation, and thorough hand washing is therefore the most crucial preventive measure. Other steps such as cohort nursing and gowns and gloves add little to the protective effect. Extra efforts should be made to protect high-risk infants admitted to paediatric wards for other reasons during the RSV season. A quarter of a century has been devoted to developing a vaccine against the RSV, but due to the remarkable antigenic heterogeneity of the virus and an incomplete understanding of the virus-host interaction, a safe and effective vaccine is probably still a long way off. Early Clinical trials of an RSV immune globulin (RSVIG) given to preterm infants have suggested that this might be a safe and effective prophylaxis in highrisk patients. Animal work on monoclonal antibodies to one of the RSV proteins also looks promising. None of these, nor the vaccine, would protect against the other viruses that cause bronchiolitis.

PROGNOSIS

Babies often take a couple of weeks after discharge to recover fully from their primary illness. Up to 80% of infants hospitalized in the first year of life with bronchiolitis will have recurrent episodes of coughing and wheezing, often mild but clinically indistinguishable from asthma, in the subsequent year. This figure gradually declines towards the background prevalence of asthma by early school years. Lung function abnormalities are detectable in these children beyond 10 years of age. Parents of infants being discharged from hospital after RSV bronchiolitis should be warned of this prognosis and advised appropriately.