Klassen, T. P. Recent advances in the treatment of bronchiolitis and laryngitis. Pediatric Clinics of North America, 44:249, 1997. INTRODUCTION 1. Acute respiratory disease is the leading cause of hospitalization in children less than 4 years old, and effective interventions have potential to avoid or shorten hospital admissions. 2. Recent randomized controlled trials provide strong evidence for use of sympathomimetics and glucocorticoids in treatment of croup and bronchiolitis, especially with development of more potent inhaled glucocorticoids such-as budesonide.-- BRONCHIOLITIS 3. Most commonly caused by viruses including RSV, human parainflUenza virus type 3, adenovirus and others. 4. Restricted, to children less than 2 years old, bronchiolitis is defined for research purposes as "first time wheezing associated with clinical evidence of viral infection in infants." 5. Disease process results from inflammatory changes. Relative contributions of smooth muscle contraction and inflammatory airway narrowing provide rational for use of bronchodilators and glucocorticoids. 6. Recent review of effectiveness of bronchodilators suggested that patients are experiencing some benefit, based on clinical scoring system (Kellner, et al. 1996). Criticism of this study includes the lack of differentiation between anticholinergic and adrenergic agents. 7. Beta-adrenergic agents provide mild benefit; Epinephrine, with potent alpha and beta effects, is much more effective. 8. Sanchez, et al. (1993) in double-blind randomized study found a significant decrease in clinical score 30 minutes after racemic epi but not after salbutamol treatment. Both drugs decreased respiratory rate. Racemic epi also decreased pulmonary resistance. 9. Menon, et al. (1995) also found a significant improvement in patients treated with L-epinephrine as compared with salbutamol on the basis of oxygenation, heart rate and discharge rate from the ED. 10. Conclusion: Epinephrine is the preferred bronchodilator compared with salbutamol or placebo 11. Recent randomized controlled trial examined use of dexamethasone in infants hospitalized with bronchiolitis and treated with salbutamol. No significant difference was found on any clinical outcome measure or length of stay in hospital (Klassen, et al., 1996). Another study found similar results (Roosevelt, et al., 1996). 12. Conclusion: Use of glucocorticoids in acute bronchiolitis is not supported by current evidence. CROUP 13. Incidence of 3/100 in children less than 6. 1.3% of children hospitalized annually with estimated cost for human parainfluenza virus types 1 and 2 of $56 million in US every year. Two most common syndromes are spasmodic croup and laryngotracheobronchitis, primarily occurring in children 6 months to 6 years. Distinction between spasmodic croup and laryngotracheobronchitis is of questionable value in deciding whether to treat a patient with croup. 15. Randomized trials and a meta-analysis have provided recent evidence to support use of glucocorticoids in patients hospitalized with croup. 16. Kuusela and Vesikari (1988) found more rapid improvement in symptoms and shorter hospital stays in 72 children treated with dexamethasone versus placebo. 17. Similar results found by Super, et al. (1989) with dexamethasone versus placebo, and by Tibballs, et al. (1992) with oral prednisone versus placebo. 18. Recent meta-analysis showed reduced incidence of intubation and greater likelihoods of clinical improvement at 12 and 24 hours with glucocorticoid treatment versus placebo (Kairys, et al., 1989). 19. Husby, et al (1993) compared nebulized budesonide with nebulized epi and concluded that safety and efficacy were similar. 20. Klassen, et al (1994) found decreased croup scores, shorter ED stays and reduced hospitalization rates in croup patients treated with budesonide versus placebo. 21. Two studies compared dexamethasone (nebulized or IM) in outpatients and found "some benefit" to dexamethasone use but also an unacceptably high risk of complications (i.e., bacterial tracheitis) especially with nebulized dexamethasone.. 22. Geelhoed, et al. (1995) found oral dexamethasone and nebulized budesonide to be superior to placebo but not significantly different from each other in clinical benefit for croup patients treated in ED. Study criticized for small sample'size. 23. There is a "growing body of evidence" that supports the concept of safe discharge, after a 3 hour period of observation,.for patients who receive racemic epinephrine in the ED, especially if they also receive glucocorticoids. 24. Waiisman, et al. (1992) found no difference in heart rate, blood pressure or croup score between patients treated with racemic epi versus L-epinephrine. PHARMACOLOGY 25. Dexamethasone: Doses of 0.15-0.6 mg/kg as a single dose are safe and effective with no evidence of advese events. 26. Budesonide:-.]Benefit within 1-2 hours of administration, low systemic bioavailability, inhibits bradykinin-induced vascular permeability. Dose of 2 mg (4mL) has been used in all studies. Doses of 2 mg bid for up to three days "seem to be safe." 27. Epinephrine: Reduces secretions and mucosal edema, smooth muscle relaxation, reduces inflammation. L-epinephrine 1:1000 dose is 5 mL for croup, and 3 mL for bronchiolitis. Racemic epi dose is 0.1 mL/kg. Tachycardia is NOT noted as a side effect and L-epi and racemic epi are not significantly different. Peak effects 30 minutes; duration 120 minutes. 28. Salbutamol: Smooth muscle relaxation, reduced inflammation, enhanced mucociliary function. Single dose of 0.3 mL/kg (1-5 mg/kg) for bronchiolitis. Hypoxemia as transient side effect due to worsening VQ mismatch. MDI with spacer or nebulizer equally effective. SUMMARY 29. Bronchiolitis Salbutamol (nebs) causes significant short-term improvement in clinical scores, but--no reduction in admission rates or length of hospital stay. Epi (nebs) results in significant improvement in clinical scores and airway resistance, as well as-, acute improvement in oxygenation, decreased time in ED and reduced admission rates. There is no evidence to support the use of glucocorticoids in patients hospitalized with bronchiolitis. 30. Croup Budesonide nebs or oral dexamethasone reduced need for hospitalization and provided acute.clinical improvement in outpatients with mild to moderate illness. Combined Budesonide nebs and oral dexamethasone may provide the best clinical outcome. Required does of oral dexamethasone for best outcome may range from 0.15-0.6 mg/kg. Patients who receive L-epi or racemic epi concomitant with glucocorticoids in the ED, may be safely discharged after a 3 hour.*observation period if clinical circumstances allow. Use of IM dexamethasone is difficult to justify in patients able to take oral medication.