Update in the Treatment of Bronchiolitis Natalie Napolitano, MPH, RRT-NPS, FAARC Research Clinical Specialist Respiratory Therapy Department The Children’s Hospital of Philadelphia

Disclosures Research Relationships: Dräger Aerogen Actuated Medical GeNO Smiths Medical Aerogen sponsoring me to be here

Objectives Define Disease AAP Guidelines New Evidence Summarize Care Recomendations

Definition: Acute, infectious, inflammatory process of both the upper and lower airways causing mucus production and obstruction of the smaller airways It may occur at all ages Highest admission rates are among those infants between the ages of 3 to 6 months Def: Viral/bacterial process causes edema and tissue necrosis of the epithelial cells lining the small airways – causing more debris in the airways increasing mucus production to try and remove it. Adults with Bronchiolitis - larger airways of adults and older children can accommodate the mucus and inflammation and not exhibit such severe symptoms as infants

Etiology & Epidemiology: Most common agent that causes Bronchiolitis is Respiratory Syncytial Virus (RSV) (50-80%) Other agents that cause Bronchiolitis are: Human enterovirus/rhinovirus (16-18%) Influenza (10-15%) Human metapneumovirus (3-19%) Parainfluenza virus (1-7%) RSV - detected in approximately 75% of infants hospitalized with Bronchiolitis under the age of 2 Bronchiolitis is primarily from a viral etiology but in rare cases can be caused from a bacteria

Etiology & Epidemiology: The infections that cause Bronchiolitis are contagious Spread via airborne droplets (sneeze, cough, and laugh) or via contact with an object that has been contaminated (tissue, toys, telephone) RSV can survive on the surface for several hours

Signs & Symptoms: In adults and older children: In infants: symptoms are those of an upper respiratory infection. In infants: high fever, severe cough, wheezing, tachypnea, retractions, nasal flaring, possible cyanosis and in infants less that 1 month, hypothermia may find otitis media, retractions, fine diffuse rales, and fine wheezing 28% of infants with have apnea – 10% will need mechanical ventilation URI Symptoms: stuffy or runny nose, sore throat, mild headache, mild cough, low-grade fever, and a general feeling of sickness Infants - symptoms can be quite severe and can lead to requiring mechanical ventilation and even death

Risk Factors: Age (less than 2 years; especially age 3 – 6 months) No history of being breast feed Prematurity Exposure to cigarette smoke Crowded living conditions (including day care) Risk factors for contracting Bronchiolitis

Treatment: Treat symptoms while the virus runs it’s course Antibiotics – if bacterial process Primary therapy: IV fluids Management of secretions Oxygen Viral process lasts 7-10 days from onset of symptoms Fluids - commonly have mild to moderate dehydration because of a decreased fluid intake secondary to respiratory distress O2 - Hypoxemia is common due to the ventilation perfusion mismatch with collapsed lower airways and/or secondary to the inability of turbulent airflow entering the lungs via obstructed airways.

AAP 2014 Guidelines for Diagnosis and Treatment: Diagnosis on history & physical examination – (1c) should NOT routinely order laboratory and radiographic studies Should NOT administer albuterol (or salbutamol) Should NOT administer epinephrine (a)Nebulized hypertonic saline should NOT be administered in the emergency department (b)may administer nebulized hypertonic saline during inpatient hospitalization 1. CXR may be helpful when not improving as expected, if the severity of illness requires further testing or if another diagnosis is expected. Randomized trails showed routine usage of CXR increased antibiotics usage without a difference in time to recovery. 2. One in four children treated with bronchodilators may have improvement in clinical scores. The use of albuterol showed to not be beneficial in shortening length of illness or hospital stay (LOS). Evaluation of pre and post therapy assessment should be evaluated during a medication trial and continuation of the medication only if there is a documented clinical response 3. studies showed no benefit in LOS or clinical score between systemic corticosteroids and placebo. Inhaled corticosteroids also showed no benefit in the acute stage of the disease. 4. therapy has marginal benefit, if any, combines with cumbersome delivery, potential health risks for caregivers, and high costs. Rolston SL, et al. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis. Pediatrics. 2014;34(5):e1474-e1502.

AAP 2014 Guidelines for Diagnosis and Treatment: 5. Should NOT administer systemic corticosteroids 6. (a)Oxygen for SpO2 < 90% in previously healthy infants (b)Continuous SpO2 monitoring is not routinely needed 7. Should NOT use CPT 8. Should NOT administer antibiotics unless concomitant bacterial infection 9. SHOULD administer NG or IV fluids when infant can not maintain hydration 6b. No clinical benefit was found with both vibration and percussion techniques. No evidence to support routine deep suctioning to the lower pharynx or larynx. 7. Airway edema and respiratory epithelial cell sloughing causes ventilation and perfusion mismatching and in turn reduction in oxygenation. Before delivering O2 therapy, the infant’s nose and mouth should be suctioned. Administration should only occur if SpO2 remains below 90%. Study out of UCSD determined that utilization on SpO2 prolonged hospitalization by an average of 1.6 days when continuous pulse oximetry was used. Our protocol discontinues the use of continuous monitoring after 24 hours or once O2 usage is discontinued (whichever is later).

AAP 2014 Guidelines for Diagnosis and Treatment: 10. Palivizumb prophylaxis ONLY to select infants with CLD, a history of prematurity, or CHD in first year of life 11. Proper hand hygiene to decreasing the spread of contaminating agents – soap and water preferred 12. Exposure to passive or second hand smoke should be eliminated or minimized 8. administered in 5 monthly doses beginning in November or December.

What can we treat with?

High Flow Nasal Cannula: McKiernan et al: a single center retrospective chart review of infants admitted to the PICU with bronchiolitis The goal of the review was to determine if the use of HFNC was related to a decrease in the rates of intubation 115 infants Rate of intubation was 23% before HFNC and 9% after HFNC (p=0.043) number needed to treat of 7 Median length of stay in the PICU reduced from 6 to 4 days (p=0.0058) The goal of the review was to determine if the use of HFNC was related to a decrease in the rates of intubation for every 7 infants treated with HFNC 1 intubation will be avoided McKiernan C, et al. High flow nasal cannula therapy in infants with bronchiolitis. J Pediatr 2010;156(4):634-638.

Why Hypertonic Saline: Mandelberg and Amirav reviewed the mechanism of action and rationale for use of hypertonic saline or high volume normal saline for viral bronchiolitis Mucus clearance failure - hydration is a key part of ensuring adequate mucus clearance via the normal mechanisms of the mucocilliary escalator Rationale for use in treatment of bronchiolitis - viral infection of the airways including the epithelium there is epithelial cell necrosis, mucosal edema, & an increase in mucus development - increases the mucin/water ratio that causes relative dehydration of the Airway Surface Liquid Layer. They reiterated the role of hydration of the airway surface liquid layer of the mucosa and how nebulized hypertonic saline is an effective therapy for this rehydration. Mucus clearance failure – not only in CF but most airway diseases Mandelberg A, Amirav I. Hypertonic saline or high volume saline for viral bronchiolitis: mechanisms and rational. Pediatr Pulmonol. 2010;45(1):36-40.

Why Hypertonic Saline: Review prior studies & determined that a decreased length of stay & improved clinical score with the use of hypertonic saline (3%) & that its use with bronchodilators is considered safe and effective Confirms that high volume normal saline or hypertonic saline does improve mucus clearance and is not a function of saline concentration but the result of total mass of NaCl added to the airway surface So 3cc 3% saline or 15cc normal saline

What’s New since 2014?

Hypertonic Saline Heikkilä & Renko 2018 Meta-analysis on hypertonic saline in bronchiolitis LOS difference 12 hours Given in ED reduced the risk of admission – margional Overall HS statistically beneficial but little clinical benefit. Hard to know which infants need intervention and which do not 25 studies Heikkilä P & Renko M. Hypertonic saline inhalations in bronchiolitis – a cumulative meta-analysis. Ped Pulm 2018;53:233-242.

Risk Factors Dadlez et al examined the early predictors of respiratory decompensation in hospitalized infants. Single center retrospective study Review of 1217 infants < 24 months admitted for bronchiolitis April 2011-March 2015 9.9% respiratory decompensation 24% Hx prematurity Bivariate analysis to determine risk factors associated with respiratory decompensation All received HFNC or higher support Dadlez NM, et al. Risk factors for respiratory decompensation among healthy infants with bronchiolitis. Hospital Pediatrics 2017;7(9):530-535.

Risk Factors

Risk Factors Created a bronchiolitis risk score to predict decompensation – tested against population Median Bronchiolitis Risk score 1.18 Increase by 1 associated with 2.7 increase in the odds of decompensation

Compared actual decompensation with the calculated risk score for each patient

Risk Factors Conclusion: Need for additional monitoring and quicker escalation for infants with risk factors: < 6 months of age Black race Hypoxemia in ED Retractions or accessory muscle use in ED Risk factors were all independent so having any of these makes the child as higher risk for decompensation

Discharge criteria Garcia-Mauriño, et al assessed the impact of a a standardized discharge protocol for infants admitted with infectious bronchiolitis. Includes O2 weaning pathway (SpO2 > 90%) & objective clinical criteria for D/C Implemented in ID unit and not other ward units Compared LOS and readmission rates within 2 weeks. Adequate hydration and D?C follow-up Garcio-Mauriño C, et al. Discharge Criteria of Bronchioitis: An Unmet Need, Ped Infectious Disease 2017. published ahead of print.

Discharge criteria Discharge Criteria: SpO2 > 90% 6-12 hours Improved/no tachypnea (WHO definition) Afebrile 24 hours or 12 with a down trend Adequate hydration and urine output Social Miscellaneous Reduced LOS 2 vs 2.8 days (p<0.001) Do difference in readmission rates Social: safe home environment and journey there and no physician concerns Misc stable or baseline mental status and tolerate home regimen.

QI Project Sustainability Multicenter QI collaborative to develop and implement bronchiolitis Quality Improvement Project with pre and post analysis design Pre data collected for 1 season Development of protocol form AAP guidelines Implemented for next season – data collected Sustainability data collected 1 year later Included pathways, order sets, and scoring systems Shadman KA, et al. Sustainability in the AAP bronchiolitis Quality Improvement project. J Hosp Med 2017;12(11):905-910.

QI Project Sustainability Showed improvement in all metric areas after implementation Sustain year – maintained all metric improvements Respiratory score use: 6.6% - 73.9% - 70.7% # bronchodilator doses: 3.1 - 1.0 - 0.8 Orders for intermittent oximetry: 40% - 68.6% - 79.2% Baseline – intervention - sustain

What was not addresses?

Mucolytics: Boogaard et al: performed a multicenter, randomized, double-blind, controlled trial studying 225 hospitalized infants with RSV bronchiolitis requiring oxygen treated with rhDNase or placebo 2.5 mg rhDNase or placebo BID until discharge no difference between placebo and inhaled rhDNase in LOS and Duration of oxygen dependence

summary Supportive therapy Watch a small group a bit closer and escalate care quicker HFNC & 3% Hypertonic Develop pathway or protocol for best practices and monitor compliance and QI outputs after implementation.

?QUESTIONS? napolitanon@email.chop.edu