1. THE LOWER AIRWAYS Pediatric Respiratory Emergencies

2. Case 1 2M male 3 day history of URTI associated with fever (38.5) Onset of difficulty feeding, increased WOB today Vitals - HR 160 RR 65 SpO2 90% on R/A T 37.9 TT, indrawing, nasal flaring, diffuse crackles and wheezes

3. Differential diagnosis of Wheeze Infection (Bronchiolitis, pneumonia) Asthma Cystic Fibrosis CHF Foreign body Anaphylaxis Croup Epiglottis Vocal cord dysfunction GERD Bronchopulmonary dysplasia

4. You think he has bronchiolitis What do you tell his parents about his illness and its natural history?

5. Bronchiolitis Viral infection  RSV, influenza, parainfluenza, echovirus, rhinovirus, adenovirus  Mycoplasm, Chlamydia Children < 2 years, peak at 2 M October to May Contact/Droplet Peak at 3-5 d Resolves 2 weeks

6. Bronchiolitis Inflammation of terminal and respiratory bronchioles  Mucus plug + edema  Airway narrowing  Decrease compliance, increase resistance  Atelectasis and overdistention

7. Bronchiolitis Clinical presentation  Wheeze, tachypnea, indrawing  URT symptoms  Fever  Hypoxemia  Apnea

8. What factors put children at increased risk of severe bronchiolitis? History of  Prematurity  BPD  CF  Congenital heart disease  Immunocompromised

9. Management You start oxygen and encourage feeding When patient not feeding well you give 20 mL/kg bolus RT asks you if you want this child to be treated with bronchodilators or steroids… What do you think?

10. Controversial Many trials done to examine use of  Epinephrine  ß-adrenergics  Steroids  IV  PO  Inhaled

11. Evidence for Epinephrine Epinephrine vs. placebo or salbutamol 5/8 showed short term improvement in clinical scores 1/8 showed fewer hospitalization 1/8 showed shorter duration of hospitalization

12. Evidence for Epinephrine Hartling et al, 2003  Meta-analysis  Epinephrine vs. bronchodilators or placebo  RCT, infants<2 years, quantitative outcome  14 studies, 7 inpatient, 6 outpatient, 1 unknown  Outpatient results  Epi better than placebo or other bronchodilators in short term (O2 saturation, RR, clinical score)

13. Evidence for Epinephrine Cochrane Systematic Review 14 RCT (1966-2003) Inpatient and outpatient treatment Epinephrine vs. placebo - outpatient (3)  Improvement at 60 minutes (1/3studies)  No difference in admission or O2 saturation Epinephrine vs. Salbutamol - outpatient (4)  O2 saturation, HR, RR improved at 60 minutes  No difference in admission

14. 13 RCT Bronchodilators vs. placebo or ipatropium 1/13 showed decreased admission 4/13 showed some clinical improvement Evidence for Bronchodilators

15. Cochrane Systematic Review 22 RCT (1966-2005) Bronchodilators vs. placebo No difference in admission or duration of hospitalization Minor improvement in oximetry and symptoms in outpatient treatment

16. Previous studies used larger doses of epinephrine  Effect may not be due to alpha affects, but higher delivery of ß-agonist

17. RCT comparing racemic epinephrine, racemic albuterol, normal saline in equivalent doses in mild/moderate bronchiolitis N = 65 (23-albuterol, 17 epi, 25 NS) 5mg of drug in 3 mL at 0 and 30 minutes Clinical assessment pre and post 3 rd dose at 60 minutes if RDAI >8 or O2 saturation < 90% R/A Final assessment at either 60 or 90 minutes

18. Required admission/home oxygen  61% albuterol, 59% epinephrine, 64% NS No difference in admission rates No difference in O2 saturation, RR ß-agonist not useful in Rx bronchiolitis

19. “ß-agonists should not be used routinely in management of bronchiolitis” Level B “A carefully monitored trial of alpha adrenergic or ß- adrenergic medications is an option…and continued only if there is a documented positive clinical response using objective means of evaluation” Level B “…it would be more appropriate that a bronchodilator trial…use salbutamol rather than racemic epinephrine”

20. What about steroids?

21. Systematic review Oral, IV and inhaled steroids Oral  6 RCT involving prednisone (1) prednisolone (2) Dexamethasone (2) Prednisolone and albuterol vs. Placebo and albuterol  Various outcomes (hospitalization, clinical score, length of stay, duration of ventilation)  1 found decreased rate of admission, 1 found increased rate of admission,1 found shorter duration of ventilation, 1 found improved clinical status  Felt data was inconclusive

22. IV  2 RCT  Dexamethasone to placebo  No benefit  Clinical score, admission, time to resolution, duration of oxygen therapy

23. Inhaled  6 RCT  Mostly used budesonide  Worse wheeze/cough at 12 months in 1  Increase readmission  No benefit shown

24. Cochrance Systematic Review 13 RCT No difference  RR  O2 saturation  Admission  Length of stay  Subsequent visits  Readmission Evidence for Steroids

25. RCT  Comparing admission to hospital and RACS 4 hours after dose of dexamethasone (1mg/kg) versus placebo January 2004 - April 2006 N = 600 (305 dexamethasone, 295 placebo) Admission  39.7% in dex vs. 41% in placebo - no difference RACS - sum of change in RDAI minus standardized score for change in RR (negative value = good response)  No difference

26. “Corticosteroid medications should not be used routinely in the management of bronchiolitis” Level B

27. CANBEST study  RDBCT  N=800  4 treatment arms  Primary outcome  Hospital admission up to 7 days after enrollment  Epi + Dex NNT 11.4 to prevent one hospitalization

28. Palivizumab Humanized, mouse monoclonal anti-RSV antibody Monthly X 5 months, 15 mg/kg IM Prevention of serious RSV lower respiratory tract infection  Children < 2 years  Chronic lung disease of prematurity  Premature ≤ 32 weeks  Hemodynamically significant cyanotic or acyanotic congenital heart disease

29. Any novel treatments?

30. Hypertonic saline Mechanism incompletely understood  Osmotic hydration  Reduction of cross-linking  Edema reduction

31. RCT, multicentre (KGH, VGH) comparing length of stay in admitted patients receiving treatment with 3% HS vs. NS N=93 (47 - HS, 49 - NS) Doses q 2h X3, q4h X5, q6h until D/C Any other treatments mixed with appropriate solution

32. Length of stay  HS 2.6 days +/- 1.9 days  NS 3.5 days +/- 2.9 days  26% reduction in LOS  P = 0.05

33. RCT comparing epinephrine 1.5 mg in 4 mL NS vs. epinephrine 1.5 mg in 4 mL of HS N = 53 (25 NS, 27 HS) Length of stay, change in clinical severity NS 4 +/- 1.9, HS 3 +/- 1.2, p < 0.05

34. Case 3 6 yo M with PMH of asthma URTI X4 days, using blue puffer Increase WOB today HR 130, RR 35, 90% on R/A Indrawing, Audible wheeze Decreased breath sounds to R Wheeze

35. How do you want to treat this child?

36. New therapies Chest 2006 129(2)246-256 RDBCT N=697 (age 11-79) Budesonide/Formoterol vs. budesonide + terbutaline Budesonide/Formoterol as maintenance/reliever  54% decrease in severe exacerbation  90% fewer hospitalizations/ED visits  77% fewer days with oral steroids

37. Evidence for Anti-cholinergics NEJM 1998 RDBCT Albuterol vs. albuterol+ IB x 2 dose N=434 (2-18 years) IB  Decreased hospitalization (27 vs 36%, p = 0.05)  Similar hospitalization rates in moderate exacerbation  Markedly different rates in severe exacerbations

38. Evidence for Anti-cholinergics 32 studies, 16 pediatric 10 studies - admission (1786 children)  Lower admission rate  NNT =13, 7 if only severe exacerbations included 9 studies - spirometry  1 or 2 doses had FEV1 difference of 12.4%  >2 doses had FEV1 difference of 16.3%

39. Evidence for Anti-cholinergics Cochrane Systematic Review 2000 13 trials Multiple doses decreased risk of admission by 25% Single doses improved lung function at 60 and 120 minutes, but no admission NNT= 12 to avoid 1 admission in kids with either moderate or severe exacerbation NNT = 7 if severe exacerbations

40. Nebulizer vs. MDI/Spacer RDBCT N = 168 (2m to 24 months) Nebulizer vs. Spacer Primary outcome  Admission rates Results  Controlled for difference in PIS  Spacer group admitted less  5% vs. 20% p=0.05

41. Nebulizer vs. MDI/Spacer RDBCT N=90 (5 -17 years) baseline FEV1 50-79% Treatment groups  6-10 puffs  2 puffs  0.15mg/kg nebulized Primary outcome  Improvement in % predicted FEV1 Results  No significant difference in % predicted FEV1 between groups

42. Nebulizer or MDI/Spacer Cochrane Systematic Review 2006 Beta agonist via wet nebulizer vs. spacer 25 outpatient trials N = 2066 children, 614 adults MDI+spacer was equivalent to wet nebulizer wrt hospital admission rates MDI+spacer in kids  Decreased length of stay in ED

43. Continuous vs. Intermittent Cochrane Systematic Review 2003 Continuous or near continuous (q 15 minutes or >4 treatments/h) vs. intermittent nebulization Continuous beneficial  Decreased admission  Most pronounced if severe exacerbation

44. Evidence for use of steroids Cochrane Systematic Review 2001 Benefit of treatment within 1 hour of ED presentation 12 trials N = 863 Reduced admission rates, NNT = 8 Most benefit  Not currently Rx with steroids  Severe exacerbation Oral steroids worked well for kids

45. Evidence for MgSO4 5 trials IV MgSO4 at any dose vs. placebo in patients < 18 y treated with beta-agonists and steroids MgSO4 reduced hospitalization NNT=4 for avoiding hospitalization

46. Evidence for MgSO4 Cochrane Systematic Review 7 trials (5 adult, 2 pediatric) N= 665 In severe subgroup  Improved PEFR, FEV1, admission rates  Improvements not seen if all patients included

47. Evidence for MgSO4 Cochrane Systematic Review 2005 Inhaled MgSO4 6 trials N=296 (2 pediatric) Heterogenous studies therefore difficult to make definitive conclusion MgSO4 with beta-agonists showed benefit  Pulmonary function  Admission rates  In severe exacerbations

48. Evidence for IV Salbutamol Cochrane Systematic Review 2001 IV salbutamol in addition to other Rx vs. placebo 15 trials N=584 No benefit  Pulmonary function  Arterial gases  Vital signs  AE  Clinical success

49. Other treatments Heliox NIPPV

50. Case 3 5 M Male Cough, fever, decreased energy and intake Tachypnea, increased wob SpO2 90% on R/A, RR 60 Crackles in RLL CXR  Consolidation in RLL

51. Epidemiology 4% of kids/y in U.S.  Decreases with increasing age < 2 years – 80% viral > 4 years – 40% viral

52. Clinical features Cough, fever, CP, tachypnea, grunting (infants), increased wob (indrawing, seesaw) Typical presentation - bacterial  Rapid onset  Fever, chills, chest pain, cough Atypical presentation – viral  Gradual onset  Malaise, h/a, cough, fever (low-grade) Significant overlap

53. Pneumonia bugs

54. Specific bugs B. pertussis 3 stages Catarrhal phase Coryza, cough lasting 1-2 weeks Paroxysmal phase Coughing fits associated with gagging, cyanosis Whoop is uncommon in infants Lasts ~ 4 weeks Recovery Cough improves over months Treatment

55. Specific bugs S. aureus  Rapid and severe C. trachomatis  50% of exposed will get conjunctivitis  5-20% pneumonia  2-19 weeks  Rarely febrile or systemically unwell  Staccatto cough

56. CXR in ambulatory setting N = 522 (2M to 59M) Randomized to CXR or no CXR Primary outcome Results  Median 7 days to recovery in both groups  CXR group  More diagnosed with pneumonia  60% vs. 52% treated with antibiotics  More follow-up appts.  No difference in consultation, admission, repeat CXR at 28 days

57. CXR Bacterial  Lobar or segmental consolidation Viral and atypical bacterial  Interstitial infiltrates  Peribronchial thickening  Atelectasis Significant overlap  Not useful in determining etiological agent

58. CXR May want to avoid in mild acute LRTI Use if 39 or toxic

59. Admission SpO2<90-93% Young age Toxic Immunocompromised RR>70 (infant), >50 (older children) Respiratory distress Apnea/grunting Not feeding or dehydrated Social concerns

60. Acknowledgements Thanks to Sarah McPherson and Jeremy Wojtowicz