in this issue of critical care , totapally et al .   evaluated the effect of albuterol on tidal breathing loops of 20 infants with respiratory syncytial virus ( rsv ) bronchiolitis .
they found that the wheeze score and the pulmonary function tests were not significantly affected by albuterol .
this is the latest of 12 randomised controlled trials in 12 years , involving 843 infants , that evaluated the effect of bronchodilators on bronchiolitis .
after so many trials , have we resolved whether bronchodilators have a role in the management of bronchiolitis , and have pulmonary function measurements been helpful ?
of the 12 most recent randomised controlled trials published in english , evaluating the effect of salbutamol or albuterol on bronchiolitis , nine ( 75% ) showed that bronchodilators had no effect . in three of these studies ,
some difference had been observed , yet it resulted in only a small transient improvement in the acute clinical score and had no effect on hospital admission rates or duration of stay in hospital . in one of these three studies , ex - premature infants who might have had some mild underlying chronic lung disease , which might have resulted in the response to bronchodilators , were not excluded .
several studies reported an increase in heart rate   or a decrease in oxygen saturation   after salbutamol or albuterol .
the effect of ipratropium bromide ( either alone or in combination with salbutamol or albuterol ) on bronchiolitis has been evaluated in four recent randomised controlled trials   and none has shown any significant effect .
in contrast , there have been five published randomised controlled trials in the last 10 years , involving 225 infants , evaluating the effect of nebulised adrenaline ( epinephrine ) on bronchiolitis .
all five ( 100% ) have shown significant clinical improvement in infants with bronchiolitis , with decreases in oxygen requirement , respiratory rate , wheeze and retractions .
the incidence of side effects is no more frequent with nebulised adrenaline than with salbutamol .
the 90-minute heart rate was often significantly lower in the adrenaline group , and although pallor was noted more frequently it was transient and of no known clinical significance .
these results suggest that mucosal swelling and mucous plugging make a greater contribution to the increased airway resistance observed in bronchiolitis than constriction of bronchial smooth muscle .
barr et al .   found a beneficial effect of inhaled adrenaline in an infant with rsv bronchiolitis who was also receiving -adrenergic receptor blockade with propranolol .
this indicates that it was most probably the -adrenergic stimulation that was improving airway obstruction by inducing arteriolar vasoconstriction in the airway mucosa and thus reducing bronchial mucosal thickness .
of the 12 randomised studies evaluating the effect of bronchodilators on bronchiolitis , only in those by totapally et al .   and sly et al .   were any pulmonary function measurements made .
totapally used tidal breathing flow - volume loops to assess the effect of albuterol on infants with bronchiolitis , and they found no significant change .
two main calculations were made : the exhaled time to reach peak expiratory flow as a fraction of total expiratory time ( tptef / te ) and the tidal volume exhaled at peak tidal expiratory flow as a fraction of total tidal volume ( vptef / ve ) .
the time needed to reach peak tidal expiratory flow is highly influenced by the activity of the laryngeal abductors and adductors , abdominal and intercostal expiratory muscles , post - inspiratory activity of the diaphragm and intercostal muscles , and vagal nerve tone .
changes in these muscle activities could cause significant alterations in tptef / te independently of changes in the resistance and compliance of airways and lung .
thus tptef / te is an insensitive measure of airway function in infants and children in comparison with vmaxfrc ( maximal flow at functional residual capacity produced by forced expiration as a result of a rapid chest compression ) and other more invasive techniques .
sly et al .   performed a randomised trial of salbutamol in infants with bronchiolitis and measured vmaxfrc and found no significant change .
sanchez   also conducted pulmonary function tests in a crossover trial comparing salbutamol with racemic adrenaline . as in other studies , administering salbutamol resulted in no change , whereas adrenaline significantly decreased pulmonary resistance .
sanchez et al . used a more invasive technique , measuring transpulmonary pressures ( with an oesophageal catheter ) , flow and volume to determine pulmonary resistance by a least - mean - square technique .
they excluded breaths in which the leak was greater than 10% , the correlation coefficient was less than 0.95 or the tidal volume was less than 0.5 ml / kg , to eliminate the analysis of shallow breaths and artefacts . leaks around the mask or around an uncuffed endotracheal tube can cause major errors in the pulmonary function measurements and lead to gross overestimation of compliance and resistance . the inspired and expired volumes need to be within 10% of each other to allow an accurate analysis .
ideally , absolute lung volume should also be measured to help in the interpretation of resistance changes ; however , this is invasive and difficult to perform .
although totapally et al . should be commended for performing pulmonary function measurements to assess further the effect of albuterol on infants with bronchiolitis , the pulmonary function results need to be interpreted with a degree of caution
. however , in view of the general lack of effect of bronchodilators in bronchiolitis in other studies , i do not think that any significant effect of albuterol on pulmonary function was missed in this study .
it also highlights the urgent need for a simple non - invasive test that can measure lung function in infants more accurately . in summary , there is no compelling evidence that bronchodilators have a role in the routine management of infants with bronchiolitis .
there is better evidence for the use of nebulised adrenaline , which results in a reduction of the airway mucosal oedema , leading to symptomatic improvement , improved pulmonary function and shorter hospital admissions .
rsv = respiratory syncytial virus ; tptef / te = exhaled time to reach peak expiratory flow as a fraction of total expiratory time ; vmaxfrc = maximal flow at functional residual capacity produced by forced expiration as a result of a rapid chest compression ; vptef / ve = tidal volume exhaled at peak tidal expiratory flow as a fraction of total tidal volume .
 over the past 12 years there have been 12 randomised control trials , involving 843 infants , evaluating the effect of salbutamol or albuterol on bronchiolitis . of these , 
 nine ( 75% ) showed that bronchodilators had no effect . in three studies a small transient improvement in the acute clinical score 
 was seen . 
 ipratropium bromide had no significant effect . 
 there have been five recent randomised trials involving 225 infants , evaluating the effect of nebulised adrenaline ( epinephrine ) on bronchiolitis . 
 all five ( 100% ) have shown significant clinical improvement , with reductions in oxygen requirement , respiratory rate and wheeze after nebulised adrenaline . 
 two showed lower hospital admission rates and earlier discharge with adrenaline . 
 a significant improvement in pulmonary resistance was observed after nebulised adrenaline but not after salbutamol or albuterol . 
 currently there is no compelling evidence that bronchodilators have a role in the routine management of infants with bronchiolitis . 
 there is better evidence for the use of nebulised adrenaline . 
None
Salbutamol, albuterol and ipratropium bromide
Nebulised adrenaline
Pathophysiology
Pulmonary function tests
Conclusion
Competing interests
Abbreviations