1. Inpatient Bronchiolitis: So Much Time and So Little To Do Alan Schroeder, MD Director, PICU Chief, Pediatric Inpatient Services Santa Clara Valley Medical Center

2. Case – urgent care Otherwise healthy 6 month old with 3 days cough, runny nose, fussiness, decreased PO intake but normal wet diapers. Otherwise healthy 6 month old with 3 days cough, runny nose, fussiness, decreased PO intake but normal wet diapers. On PE, T=101, RR = 50, O2 Sat = 94%, HR = 160, fussy but consolable, adequately hydrated, lots o’ snot, expiratory wheezes, mild SC&IC rtxns On PE, T=101, RR = 50, O2 Sat = 94%, HR = 160, fussy but consolable, adequately hydrated, lots o’ snot, expiratory wheezes, mild SC&IC rtxns

3. Results SPO2 = 94% RR = 50 (n=119) SPO2 = 94% RR = 65 (n=125) SPO2 = 92% RR = 50 (n=124) SPO2 = 92% RR = 65 (n=117) Would admit (%) 43588385 Bronchodilator (%) 92959798 O2 (%) 34397981 Nasal Suction (%) 80828580 Steroids (%) 76811 Abx (%) 2223 Mallory, Pediatrics, 2003

4. Management Dilemmas in Bronchiolitis Nebs? Nebs? Albuterol vs racemic epinephrine? Albuterol vs racemic epinephrine? Hypertonic saline? Hypertonic saline? Suctioning (+/- saline)? Suctioning (+/- saline)? Chest Physiotherapy? Chest Physiotherapy? If febrile, R/O SBI? If febrile, R/O SBI? CXR? CXR? Steroids? Steroids? Decongestants? Decongestants? Abx? Abx? When to admit? When to admit? O2 Sat criteria? O2 Sat criteria? Risk of apnea? Risk of apnea? Safe to eat? Safe to eat? When to discharge? When to discharge?

5. Bronchiolitis Overview #1 cause of infant hospitalization #1 cause of infant hospitalization 1/3 of all children get bronchiolitis in first 2 years 1/3 of all children get bronchiolitis in first 2 years 1/30 children get hospitalized 1/30 children get hospitalized 150,000 hospitalizations per year 150,000 hospitalizations per year 1.5M annual outpatient visits for RSV alone 1.5M annual outpatient visits for RSV alone $500-700M/year $500-700M/year

6. Bronchiolitis – Definition “a seasonal viral illness characterized by fever, nasal discharge, and dry, wheezy cough. On examination there are fine inspiratory crackles and/or high-pitched expiratory wheeze” www.nottingham.ac.uk/paediatric-guideline/breathingguideline.pdf.

7. Why have hospitalization rates increased? Increased survival of children with comorbidities Increased survival of children with comorbidities ? Virulence ? Virulence Increase in daycare Increase in daycare Changes in hospitalization criteria Changes in hospitalization criteria

8. Bronchiolitis seasonality MMWR, 2009

9. Pathophysiology Inflammed/ edematous bronchial walls Inflammed/ edematous bronchial walls WBC’s (mostly monos) infiltrate bronchiolar epithelium WBC’s (mostly monos) infiltrate bronchiolar epithelium Mucus plugs block airway Mucus plugs block airway http://www.health-healths.com/tag/prevention/page/5

10. Pathphysiology Mucus plugging  one-way valve  hyperinflation  absorption atalectasis --> V:Q mismatch Mucus plugging  one-way valve  hyperinflation  absorption atalectasis --> V:Q mismatch Smooth-muscle constriction (bronchiolespasm) not a factor Smooth-muscle constriction (bronchiolespasm) not a factor

11. Clinical presentation URI symptoms first URI symptoms first Spreads to LRT – cough, tachypnea more present Spreads to LRT – cough, tachypnea more present Fever in ~ 50% Fever in ~ 50% Poor po intake, decreased UOP Poor po intake, decreased UOP

12. Exam

13. Concerning clinical findings Lethargy/extreme irritability Lethargy/extreme irritability Dehydration Dehydration Respiratory distress Respiratory distress Apnea Apnea

14. Outline

15. SCVMC and MARC-30 study MARC = Multicenter Airway Research Collaboration MARC = Multicenter Airway Research Collaboration Part of Emergency Medicine Network (EMNet) Part of Emergency Medicine Network (EMNet) Prospective, multicenter. Prospective, multicenter. 16 sites, 2200 patients over 3 winters (11/07 – 4/10) 16 sites, 2200 patients over 3 winters (11/07 – 4/10) NIH funded (NIAID) NIH funded (NIAID) PI: Carlos Camargo (Mass General), Jonathan Mansbach (Boston Children’s) PI: Carlos Camargo (Mass General), Jonathan Mansbach (Boston Children’s) Aims: Aims: Elucidate role of co-infections Elucidate role of co-infections Identify predictors of PPV Identify predictors of PPV Establish evidence-based discharge criteria Establish evidence-based discharge criteria

17. Viral co-infections

18. Virology - Implications Cohorting/isolation? Cohorting/isolation? Comfort of diagnosis? Comfort of diagnosis? Utilization of resources? Utilization of resources? Hospital charges: Hospital charges: Flu A, B, RSV ($220) Flu A, B, RSV ($220) Para 1,2,3 ($220) Para 1,2,3 ($220) Bordetella pertussis, B. parapertussis ($95) Bordetella pertussis, B. parapertussis ($95)

19. Virology - implications My conclusion: run-of-the-mill bronchiolitis does not warrant viral testing My conclusion: run-of-the-mill bronchiolitis does not warrant viral testing Possibly for influenza Possibly for influenza only 19/2200 (~1% of patients in cohort) only 19/2200 (~1% of patients in cohort) Same goes for CXR, labs, even if febrile Same goes for CXR, labs, even if febrile UA/Urine Cx if < 90 days? [Ralston, Arch Pediatr Adol Med 2011] UA/Urine Cx if < 90 days? [Ralston, Arch Pediatr Adol Med 2011]

20. Outline

21. Steroids? 2003 Cochrane (Patel et al): 2003 Cochrane (Patel et al): “Available evidence suggests that corticosteroid therapy is not of benefit in this patient group” “Available evidence suggests that corticosteroid therapy is not of benefit in this patient group” 13 trials 13 trials AAP recs (2005): AAP recs (2005): “Corticosteroids should not be used routinely in the management of bronchiolitis” “Corticosteroids should not be used routinely in the management of bronchiolitis”

22. B-agonists Cochrane 2010 (Gadomski and Brower): Cochrane 2010 (Gadomski and Brower): 28 trials (1912 infants) 28 trials (1912 infants) No reduction in admission or length of hospitalization No reduction in admission or length of hospitalization Transient reduction in clinical score Transient reduction in clinical score AAP (2005): AAP (2005): “bronchodilators should not be used routinely in the management of bronchiolitis…” “bronchodilators should not be used routinely in the management of bronchiolitis…” “…A carefully monitored trial of beta or alpha agonist is an option” “…A carefully monitored trial of beta or alpha agonist is an option”

23. Epinephrine Cochrane 2011 (Hartling et al) Cochrane 2011 (Hartling et al) 19 studies, 2256 patients 19 studies, 2256 patients RR admissions on Day 1 in outpatients =.67 (.50-.89) vs placebo RR admissions on Day 1 in outpatients =.67 (.50-.89) vs placebo Shorter LOS for epi vs salbutamol Shorter LOS for epi vs salbutamol

24. Epi + dexamethasone? Pediatric Emergency Research Canada RCT [Plint et al, NEJM 2009] Pediatric Emergency Research Canada RCT [Plint et al, NEJM 2009] 800 kids 800 kids 4 arms: 4 arms: Decadron Decadron Racemic epi Racemic epi Decadron + epi Decadron + epi Placebo Placebo Marginal benefit in admission rate by 7 days in decadron + epi group (17% vs 26%) Marginal benefit in admission rate by 7 days in decadron + epi group (17% vs 26%)

25. Hypertonic saline Zhang et al, Cochrane 2008 Zhang et al, Cochrane 2008 4 trials, 254 patients, with/without bronchodilators 4 trials, 254 patients, with/without bronchodilators ↓LOS by 1 day ↓LOS by 1 day Reduced clinical score in outpatients Reduced clinical score in outpatients 4 additional RCTs 4 additional RCTs 2 with some benefit (Al-Ansari et al, J Peds 2010; Luo et al, Clin Microb Inf, 2011) 2 with some benefit (Al-Ansari et al, J Peds 2010; Luo et al, Clin Microb Inf, 2011) 2 with no benefit (Kuzik et al, CJEM 2010; Grewal et al, Arch Pediatr Adol Med 2009) 2 with no benefit (Kuzik et al, CJEM 2010; Grewal et al, Arch Pediatr Adol Med 2009)

26. Hypertonic saline Bronchodilators necessary? [Ralston et al, Pediatrics, 2010] Bronchodilators necessary? [Ralston et al, Pediatrics, 2010] 1 episode of bronchospasm in 377 doses of HS without bronchodilator 1 episode of bronchospasm in 377 doses of HS without bronchodilator So why not? So why not? (We’ve been down this path before…) (We’ve been down this path before…)

27. Pediatrics, 2011 Increasing inpatient bronchiolitis volume  reduced steroids, xrays, laboratory tests Increasing inpatient bronchiolitis volume  reduced steroids, xrays, laboratory tests

28. Pediatrics 2000 6 RCTs, included 2 trials that did not exclude prior wheezers 6 RCTs, included 2 trials that did not exclude prior wheezers Conclusion: “Published reports of the effect of systemic corticosteroids on the course of bronchiolitis suggest a statistically significant improvement in clinical symptoms, LOS, and DOS.” Conclusion: “Published reports of the effect of systemic corticosteroids on the course of bronchiolitis suggest a statistically significant improvement in clinical symptoms, LOS, and DOS.”

29. Nasal decongestants Ralston et al, J Peds 2008 Ralston et al, J Peds 2008 41 infants, phenylephrine vs placebo 41 infants, phenylephrine vs placebo No benefit No benefit

30. Chest PT Gajdos et al, PLOS, 2010 Gajdos et al, PLOS, 2010 Multicenter RCT of CPT (forced expiratory techniques and assisted cough) vs nasal suction Multicenter RCT of CPT (forced expiratory techniques and assisted cough) vs nasal suction 496 infants, no benefit 496 infants, no benefit Roque, Cochrane 2012 Roque, Cochrane 2012 9 trials (5 vibration/percussion, 4 passive expiratory) 9 trials (5 vibration/percussion, 4 passive expiratory) No benefit No benefit

31. Heliox Less turbulent airflow through resistant airways Less turbulent airflow through resistant airways When given in ED with racemic epi + via HFNC, small improvement in clinical scores but no reduction in admission or LOS [Kim et al, APAM 2011] When given in ED with racemic epi + via HFNC, small improvement in clinical scores but no reduction in admission or LOS [Kim et al, APAM 2011] Mixed results in ICU setting [Martinon-Torres et al, Pediatrics 2002; Liet et al, J Peds 2005] Mixed results in ICU setting [Martinon-Torres et al, Pediatrics 2002; Liet et al, J Peds 2005]

32. O2 Sat: why does it matter? It can be easily fixed!! It can be easily fixed!! May predict respiratory failure or ICU transfer in early phase of disease May predict respiratory failure or ICU transfer in early phase of disease May predict readmission May predict readmission ?May be deleterious to the developing brain? ?May be deleterious to the developing brain? Commentary to 2005 AAP guidelines (Cutoff = “persistently below 90%”): “It is unfortunate that the recommendation fails to address another significant consideration, viz, the impact of chronic or intermittent hypoxia on later cognitive and behavioral outcomes.”[Bass, Pediatrics 2007] Commentary to 2005 AAP guidelines (Cutoff = “persistently below 90%”): “It is unfortunate that the recommendation fails to address another significant consideration, viz, the impact of chronic or intermittent hypoxia on later cognitive and behavioral outcomes.”[Bass, Pediatrics 2007] Site articles suggesting some detriment at 90-94% (in pts with CHD or OSA!!!) Site articles suggesting some detriment at 90-94% (in pts with CHD or OSA!!!)

33. Oxygen LOS prolonged by perceived need for O2 LOS prolonged by perceived need for O2 26% - 57% of hospitalized patients [Schroeder, Archives Ped Adol Med 2004; Unger, Pediatrics 2008] 26% - 57% of hospitalized patients [Schroeder, Archives Ped Adol Med 2004; Unger, Pediatrics 2008] AAP: AAP: “As child’s course improves, continuous O2 monitoring is not routinely needed” “As child’s course improves, continuous O2 monitoring is not routinely needed” Ongoing RCT of continuous vs intermittent pulse oximetry Ongoing RCT of continuous vs intermittent pulse oximetry

34. Summary No frittering No frittering Resist temptation to treat all wheezing Resist temptation to treat all wheezing Racemic epinephrine instead of albuterol? Racemic epinephrine instead of albuterol? Limited utility of NP swabs Limited utility of NP swabs Search for the holy grail continues Search for the holy grail continues

35. More to come from MARC-30 Predicting safe discharge Predicting safe discharge Predicting PPV Predicting PPV Better understanding of apnea and the associated viruses Better understanding of apnea and the associated viruses Role of vitamin D levels Role of vitamin D levels Development of asthma after bronchiolitis Development of asthma after bronchiolitis