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Journal of Paediatric Respirology and Critical Care Evidence based management of acute bronchiolitis Sou-Chi SIT
Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong
Bronchiolitis is a common acute lower respiratory tract routine use of salbutamol is not recommended judging disease affecting infants. It is associated with viral infection and respiratory syncytial virus is the mostfrequently identified microorganism. Bronchiolitis As compared with salbutamol, ipratropium bromide remains one of the major reason for hospitalisation is less controversial. No significant effect on the in children younger than 1-year. Its presentation is clinical outcomes was documented with ipratropium characterised by fever, coryza, cough, expiratory bromide in two systemic reviews by Schindler et al wheezing and distress. There were numerous clinical and King et al respectively.4,5 Therefore, use of s t u d i e s p u b l i s h e d o n t h e e ff i c a c y o f v a r i o u s ipratropium bromide in bronchiolitis is not advised.
medications used in managing this disease. However,the results of many of these studies were conflicting.
Hence, controversies still exist concerning thepharmacological treatment of bronchiolitis. In this A recently published meta-analysis by Hartling et al article, the current evidence from the recently investigated the efficacy of epinephrine in treating published literature on different drugs given for acute bronchiolitis.6 Fourteen randomised controlled trial bronchiolitis will be discussed. These include were included of which they were further categorised salbutamol, ipratopium bromide, epinephrine, steroid, into inpatient and outpatient studies for analysis.
Clinical score was the only outcome found to befavouring epinephrine with the standardised mean Bronchodilator
difference (SMD) of -0.52 (CI -1.00, -0.03) among theinpatient studies comparing epinephrine and placebo.
There were four meta-analyses and one systemic For the outpatient studies (3 trials), 5 outcomes review investigating the efficacy of bronchodiliators including the clinical score at 60 minutes, change in in treating bronchiolitis. Salbutamol was the most oxygen saturation at 30 minutes, respiratory rate at frequently used bronchodilator among the clinical 30 minutes and improvement favoured epinephrine.
studies. Kellner et al found in his two meta-analyses There was no significant difference in admission rate that bronchodilator produced short term improvement between the treatment and control group. The authors in the clinical score.1,2 Its administration was not also compared the effect of epinephrine and associated with any significant adverse effect.
salbutamol in both inpatient and outpatient studies.
However, the magnitude of reduction in clinical score Respiratory rate at 30 minutes was the only outcome was small between the treatment and control group out of seven detected to be improved in the adrenaline (pooled difference in clinical score -0.2; 95% CI -0.37 group with weighted mean difference of -5.12 (95% to -0.1). The clinical importance is therefore CI -6.83, -3.41). Among the four outpatient studies, questionable. There was also no significant difference change in oxygen saturation at 60 minutes, heart rate observed in the rate and duration of hospitalisation at 90 minutes, respiratory rate at 60 minutes and between both groups. For the remaining three studies, "improvement" favoured epinephrine over salbutamol.
the authors did not find any evidence to suggest that The evidence is not sufficient to support use of use of salbutamol was associated with consistent epinephrine in the treatment of bronchiolitis among c l i n i c a l i m p r o v e m e n t i n h o s p i t a l i s a t i o n r a t e , inpatients. There is some evidence to suggest the physiological parameters or clinical scores.3-5 Thus, efficacy of epinephrine among outpatients but all thestudies only investigated short term effect. A largeand high quality trials is needed to substantiate the Author to whom correspondence should be addressed.
effect of epinephrine. Meanwhile, use of nebulised epinephrine should not be routinely recommended.
steroid in managing severe bronchiolitis. Owing to theconflicting evidence, steroid should only be given to The trials for steroid in the management of acute patients with severe bronchiolitis after careful bronchiolitis can be classified according to the types of patients involved in the studies namely inpatients,outpatients and intensive care patients.
A meta-analysis by Garrison et al concluded that A recent systemic review by King and his colleagues systemic steroid was beneficial for treatment of included 10 trials to investigate the effect of ribavirin bronchiolitis by demonstrating improvement in length for treatment of bronchiolitis.5 No significant difference of stay and duration of symptoms.7 However, five out on days of hospitalisation, length of time for intensive of six included studies showed little or no beneficial supportive interventions and duration of illness was effect and the actual benefit demonstrated was detected. Three out of six trials reporting clinical score qualitatively small, i.e. less than half a day difference and symptoms as their outcome did not find any in hospitalisation. Hence, the result of this meta- improvement after treatment with ribavirin. The results analysis should be interpreted cautiously. In addition, of the remaining three trials reporting positive effect two other inpatient trials published in recent few years were not entirely consistent. The authors therefore failed to document any positive effect with the use of concluded that no evidence of ribavirin use led to steroid.8,9 There is currently inadequate evidence to consistent or more than transient improvements in support routine use of steroid in hospitalised patients In another systemic review published in Cochrane In contrast to the inpatient studies, three recently Library 2004, the investigators found reduction in published trials performed in the emergency mortality (OR 0.58; 95% CI 0.18 to 1.85), probability department have shown that systemic steroid was of respiratory deterioration (OR 0.37; 95% CI 0.12 to effective in reduction of clinical score, duration of 1.18), days of hospitalisation (weight mean difference symptoms and hospitalisation.10-12 The corticosteroid (WMD) of 1.9 days; 95% CI -4.6 to +0.9) and days of used in the trials included 2 mg/kg of prednisolone ventilation (WMD of 1.8 days; 95% CI -3.4 to -0.2) in for 3 to 5 days and one dose of 1 mg/kg of dexa- infants and young children with respiratory syncytial methasone. Weinberger et al commented that the virus infection of the lower respiratory tract with the observed effect could have been explained by the use of ribavirin.17 However, the included trials were early treatment provided in the emergency department small and lacked sufficient power to provide reliable when the inflammation of airway was still reversible.13 estimate of the effects. A large RCT on ribavirin A large and well designed RCT is certainly required treatment for severe bronchiolitis is indicated to further to confirm the efficacy on early initiation of steroid therapy. Though, the existing evidence may not besufficient to recommend routine administration of Montelukast
steroid to patients with bronchiolitis in the outpatientsetting, its use may be considered taking into account Bisgaard and his groups described their observation on the effect of montelukast on symptoms of RSVbronchiolitis.18 Infants were free of any symptoms on In the subgroup analysis of two separate studies by 22% of the days and nights after receiving 28 days of van Woensel et al, systemic steroid shortened the montelukast therapy whereas patients on placebo had duration of mechanical ventilation, supplemental 4% of symptom-free days and nights (p=0.015). Also, oxygen and hospital stay in bronchiolitis patients the day time cough was reduced and exacerbation requiring mechanical ventilation.14,15 However, another was delayed significantly in the montelukast-treated trial performed on critical ill patients with bronchiolitis group. However, this study was designed to evaluate did not detect any significant difference in clinical the treatment effect on postbronchiolitis symptom and outcomes of the steroid treated group.16 Further large its role on acute symptom has not been addressed.
scale trial is warranted to document the benefit of To date, this study is the only trial reporting the use Journal of Paediatric Respirology and Critical Care of montelukast in the management of bronchiolitis.
CS, et al. Long and short-term effect of prednisolone in More studies are needed to determine the efficacy of hospitalized infants with acute bronchiolitis. J Paediatr Child montelukast on acute symptoms of bronchiolitis before any recommendation can be made on its use.
10. Goebel J, Estrada B, Quinonez J, Nagji N, Sanford D, Boerth RC. Prednisolone plus albuterol versus albuterolalone in mild to moderate bronchiolitis. Clin Pediatr (Phila) In summary, many studies identified for drugs given in bronchiolitis were underpowered and their results 11. Schuh S, Coates AL, Binnie R, Allin T, Goia C, Corey M, et were not uncommonly conflicting. Large trials on al. Efficacy of oral dexamethasone in outpatients with acute individual medications are definitely indicated to bronchiolitis. J Pediatr 2002;140:27-32.
provide clinicians with adequate guidance for an 12. Csonka P, Kaila M, Laippala P, Iso-Mustajarvi M, Vesikari evidence based approach in management of this T, Ashorn P. Oral prednisolone in the acute management common disease of paediatric patients.
of children age 6 to 35 months with viral respiratoryinfection-induced lower airway disease: a randomized, References
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14. van Woensel JB, Wolfs TF, van Aalderen WM, Brand PL, 2. K e l l n e r J D , O h l s s o n A , G a d o m s k i A M , Wa n g E E .
Kimpen JL. Randomised double blind pacenbo controlled Bronchodilators for bronchiolitis (Cochrane Review). In: The trial of prednisolone in children admitted to hospital with Cochrane Library, Issue 4 2002. Oxford: Update Software.
respiratory syncytial virus bronchiolitis. Thorax 1997;52: 3. Flores G, Horwitz RI. Efficacy of beta 2 agonists in bronchiolitis: a reappraisal and meta-analysis. Pediatrics 15. van Woensel JB, van Aalderen WM, de Weerd W, Jansen NJ, van Gestel JP, Markhorst DG, et al. Dexamethasone 4. Schindler M. Do bronchodilators have an effect on for treatment of patients mechanically ventilated for lower bronchiolitis? Crit Care 2002;6:111-2.
respiratory tract infection caused by respiratory syncytial 5. King VJ, Viswanathan M, Bordley WC, Jackman AM, Sutton SF, Lohr KN, et al. Pharmacologic treatment of bronchiolitis 16. Buckingham SC, Jafri HS, Bush AJ, Carubelli CM, Sheeran in infants and children: a systematic review. Arch Pediatr P, Hardy RD, et al. A randomized, double-blind, placebo- controlled trial of dexamethasone in severe respiratory 6. Hartling L. Epinephrine for bronchiolitis (Review). The syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome. J Infect Dis 2002;185:1222-8.
7. Garrison MM, Christakis DA, Harvey E, Cummings P, Davis 17. Ventre K, Randolph A. Ribavirin for respiratory syncytial RL. Systemic corticosteroids in infant bronchiolitis: a meta- virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev 2004; 8. Berger I, Argaman Z, Schwartz SB, Sagal E, Kiderman A, Branski D, et al. Efficacy of corticosteroids in acute 18. Bisgaard H; Study Group on Montelukast and Respiratory bronchiolitis: short-term and long-term follow-up. Pediatr Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir 9. Zhang L, Ferruzzi E, Bonfanti T, Auler MI, D'avila NE, Faria



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