Evidence Based Management of Bronchiolitis

Celeste A. Tarantino, M.D.

Childrens Mercy Hospital and Clinics

Objectives
To review the etiology, epidemiology and pathophysiology of bronchiolitis To define and review the clinical presentation of bronchiolitis To review the evidence in the management of bronchiolitis Infection control, prevention and prophylaxis will not be covered

Infant A History
A 9 wk old female presents with a CC of congestion. She has a 2 day history of cold, congestion, runny nose, tactile temperature and decreased breastfeeding. No V/D. Good UO. PMH-full term infant, P/L/D non-complicated, SVVD. Birth Wt 7#. FH/SH-lives with both parents & 2 siblings in a non-smoking home; no daycare; both siblings are ill with same sxs; neg asthma.

Infant A Physical Exam

VS-Temp 38.3, HR 140, RR 48 Alert, vigorous, nonill, mild IC & SC retractions Copious clear nasal secretions Diffuse coarse BS with UAC and expiratory wheezes Oxygen saturation > 95% on room air RSV screen positive

Infant A Clinical Course

Infant had her nostrils suctioned with saline using a bulb suction She breast fed well & was observed for 1 hr She had no increase in respiratory difficulty She did not develop an oxygen need She was discharged with a diagnosis of bronchiolitis and fever The parents were instructed to continue to bulb suction with saline, return for poor feeding, poor color or difficulty breathing and to see their PCP the next day

Infant B History
A 4 wk old male infant & his twin brother present with a CC of spitting up. Parents report a 2 day history of decrease po intake & spitting up with feeds. Mom reports an episode where the infant stopped breathing & had brief duskiness after a feed. She denies any respiratory difficulty & says the baby began breathing after 10-15 secs. Sleeping more than usual. Denies runny nose, cough or fever. Twin has a cough. PMH-Twin A, born @ 37 wks via repeat c-section, P/L/D noncomplicated. B Wt 5# 13oz. FH/SH-lives with both parents, twin & 2 older siblings in a nonsmoking home; older sibling has cold symptoms

Infant B Physical Exam

VS-T 37.0, HR 178, RR 44, Wt. 3.29 Pink, good tone, a little sleepy BS clear, good aeration, no increased WOB, rare cough Oxygen saturation 100% on room air RSV screen positive

Infant B Clinical Course

After a long discussion with the parents both infants were admitted due to age, poor feeding & parental concern Shortly after arrival to the floor the patient developed witnessed episodes of apnea with bradycardia and cyanosis that responded well to stimulation Infant placed on L O2 via NC and transferred to the PICU CXR showed hyperinflation vs. viral process He had no further events and was discharged to home after 2 day LOS

Definition
Bronchiolitis is a common disease in infants and young children due to inflammatory obstruction of the bronchioles resulting from a viral lower respiratory tract infection (LRTI)

Definition
Bronchiolitis is a constellation of clinical symptoms and signs including a viral upper respiratory prodrome followed by increased respiratory effort and wheezing in children less than 2 years of age

AAP, Subcommittee on Diagnosis and Management of Bronchiolitis. Pediatrics. 2006; 118 (4): 1774-1793

Etiology
Respiratory Syncytial Virus (RSV) accounts for > 50% of infections RSV is an enveloped RNA paramyxovirus Other viral pathogens include parainfluenza, metapneumovirus, influenza & adenovirus No evidence of a bacterial cause for bronchiolitis

Epidemiology
Most common LRTI in the 1st 2 years of life Approximately 100,000 hospitalizations annually in U.S. Highest rate of infection occurs between Dec-March 90% of children become infected with RSV by age 2 40% of children infected with RSV will have LRTI Infection with RSV does not give life-long immunity Infection in older children & adults presents as URI

Epidemiology
Humans are the only source of infection Transmission occurs by direct or close contact with contaminated secretions RSV is unstable in the environment, surviving only a few hrs RSV may persist for > 30mins on hands; readily inactivated with soap & water and disinfectants Spread among household & child care contacts is common Incubation period averages 4-6 days (range 2-8) Viral shedding lasts 3-8 days, may be as long as 3-4 wks

Pathophysiology
Not all infected infants develop LRTI Bronchiolar obstruction with edema, mucous & cellular debris Minor bronchiolar wall thickening may significantly affect airflow (R=1/r4)

Signs and Symptoms

URI Rhinorrhea Congestion Sneezing Cough Poor appetite Fever Respiratory difficulty Tachypnea Wheezing Crackles Apnea

Physical Exam Findings

Rhinorrhea Congestion Cough Tachypnea (RR > 60) Respiratory distress-retractions, nasal flaring and grunting Crackles Wheezes Poor aeration

Differential Diagnosis for a Wheezing Infant

Viral bronchiolitis Other pulmonary infections (eg, pneumonia, Mycoplasma, Chlamydia, tuberculosis) Laryngotracheomalacia Foreign body, esophageal or aspirated Gastroesophageal reflux Congestive heart failure Vascular ring Allergic reaction Cystic fibrosis Mediastinal mass Bronchogenic cyst Tracheoesophageal fistula

Goals in Assessment
Differentiation of infants with probable bronchiolitis from those with other disorders Estimation of the severity of illness

Diagnosis of Bronchiolitis
AAP Clinical Practice Guidelines
Clinicians should diagnose bronchiolitis & assess disease severity on the basis of HX & PE. Clinicians should not routinely order laboratory & radiographic studies for diagnosis Clinicians should assess risk factors for severe disease such as age < 12 weeks, a hx of prematurity, underlying cardiopulmonary disease, or immunodeficiency when making decisions about evaluation & management of children with bronchiolitis

Risk Factors for Severe Disease

Several studies have identified prematurity (< 37 wks EGA) & young age (< 6-12 wks) with increased risk of severe disease Young infants may develop apnea Increased risk of severe disease or mortality Congenital heart disease Chronic lung disease (BPD, CF, congenital anomaly) Immunocompromised state

What About Apnea?

Retrospective study of 691 hospitalized infants < 6 mos age Apnea in 19 (2.7%) Identified risk criteria
History of apneic episode Young age
< 1 month age for term infants < 48 wks postconceptional age for premature infants

Factors Associated with Severe Illness

Ill or toxic appearance Oxygen saturation < 95% Gestational age < 34 weeks RR > 70 breaths/min Age < 3 months Co morbidities Rapid progression of symptoms

Chicken or Egg?
Unclear whether severe viral illness early in life predisposes children to develop recurrent wheezing or if infants who experience severe bronchiolitis have an underlying predisposition to recurrent wheezing

Treatments to Consider
Is laboratory testing necessary to diagnose infants with bronchiolitis? Is a chest x-ray necessary for infants with bronchiolitis? Should bronchodilators be used routinely in the treatment of bronchiolitis? Should racemic epineprhine be used routinely in the treatment of bronchiolitis? Is nasal suctioning beneficial in the treatment of bronchiolitis? Should antibiotics be used routinely in the treatment of bronchiolitis? Is there a role for hypertonic saline?

What does the evidence say about lab testing?

No evidence to support routine CBC & Diff w/ platelets No evidence to support routine BMP RSV routine testing is generally not indicated Numerous studies demonstrate rapid RSV testing with high sensitivity & specificity No evidence to support routine RSV testing affects clinical outcomes in typical disease

RSV Testing
Rapid Ag
Rapid results Sensitivity 70-90%, specificity > 95%

Resp Viral Panel PCR

Results within 1 day Detects both live & dead virus High sensitivity & specificity Reserve for use inpatient testing if highly suspicious and other testing neg

RSV Testing
Resp Viral Cx Gold standard to detect viral infection Includes tube and shell vial culture Isolation affected by specimen collection or transport Positive results in 1-2 days, final in 10 days Common respiratory viruses grow in shell vial Reserve tube cx for immunocompromised & severly ill Resp Shell Vial Cx RSV grows readily in shell vial cx Best choice for resp viruses (RSV, Flu A & B, Adenovirus, Parainfluenza 1, 2 & 3, hMPV) Positive results in 2 days

RSV Testing CO$T

RSV rapid Ag=$144 RSV PCR=$667 Respiratory viral Cx=$686
If positive, add $188 for identification

Respiratory shell vial=$188

If positive, add $188 for identification

Evidence on use of routine chest x-rays

Swingler et al-RCT of 522 infants & children aged 2-59 months, CXR + vs. CXR CXR+: more likely to be diagnosed with pneumonia or URI & receive antibiotics CXR-: more likely to be dxed bronchiolitis Median time to recovery 7 days both groups

Evidence of use of routine CXR

Prospective study of pts 2-23 months in ED showed low yield of routine CXR In 2 of 265 uncomplicated pts, routine CXR identified findings inconsistent with bronchiolitis Findings did not change acute management

CXR Findings
Approximately 25% of hospitalized infants with bronchiolitis have radiographic evidence of atelectasis or infiltrates often misinterpreted as possible bacterial pneumonia Bacterial pneumonia in infants with bronchiolitis without consolidation is unusual

Reviewing the evidence: bronchodilators

RCTs failed to demonstrate consistent benefit Cochrane systematic review found 8 RCTs involving 394 children Some studies included children with prior wheezing Some studies used ipratropium & metaproterenol other than albuterol & epinephrine 1 in 4 demonstrated transient response

What about Albuterol specifically?

Studies have demonstrated improvement in O2 saturation and/or clinical scores 2 studies show improvement in O2 saturation & clinical scores shortly after completion of treatment. No measurements over time Klassen et al. evaluated clinical score & O2 saturation 30 & 60 mins after a single treatment. Improvement in clinical score but not O2 sat at 30 minutes but no change after 60 mins Gadomski et al.-no difference between albuterol & placebo after 2 nebulized treatements given 30 mins apart

Albuterol in the hospital

Dobson et al. conducted a RCT in infants hospitalized with viral bronchiolitis failed to demonstrate clinical improvement Two meta-analyses could not directly compare inpatient studies of abuterol because of widely differing methodology. Overall, the studies reviewed did not show the use of albuterol in infants with bronchiolitis to be beneficial in shortening duration of illness or length of hospital stay

What about Epinephrine?

Multicenter study by Wainwright et al. concluded epinephrine did not impact the overall course of illness measured by hospital length of stay Several studies compared epinephrine to albuterol or epinephrine to placebo. Racemic epinephrine has demonstrated slightly better clinical effect than albuterol. Meta-analysis by Hartling et al suggests epineprhine may be favorable to albuterol Cochrane review There is insufficient evidence to support the use of epineprine for the treatement of bronchiolitis among inpatients. There is some evidence to suggest that epinephrine may be favorable to albuterol and placebo among outpatients.

The Role of Bronchodilators

AAP Clinical Practice Guidelines
Bronchodilators should not be used routinely in the management of bronchiolitis A carefully monitored trial of -adreneric & adrenergic medication is an option. Inhaled bronchodilators should be continued only if there is a documented positive clinical response to the trial using an objective means of evaluation.

What does the evidence show for steroids?

Available evidence suggests that corticosteroid therapy is not of benefit in this patient group Cochrane data base review included 13 studies & 1198 patients
Decrease LOS of 0.38 days-not statistically significant No benefits in LOS or clinical score in infants & young children treated with steroids vs placebo 2 available studies evaluated inhaled corticosteroids showed no benefit in the course of acute disease 3 studies evaluated hospital admission rates
No difference in respiratory rate No difference in O2 saturation No difference in hospital revisit rate No difference in readmission rate

The Role of Corticosteroids

AAP Clinical Practice Guidelines
Corticosteroid medications should not be used routinely in the management of bronchiolitis

Cochran Review of Hypertonic Saline

Hypertonic saline=concentration > 3% 4 RCT, 254 infants: 189 inpatients & 65 outpatients Infants < 24 mos age with acute bronchiolitis Confirmation of viral etiology not necessary Excluded pts with recurrent wheezing

Cochran Review of Hypertonic Saline

Nebulized hypertonic saline alone vs. nebulized 0.9% saline Nebulized hypertonic saline + bronchodilator vs. nebulized 0.9% saline Nebulized hypertonic saline + bronchodilator vs. nebulized 0.9% saline + same bronchodilator Nebulized hypertonic saline + bronchodilator vs. no intervention

Cochran Review of Hypertonic Saline

Nebulized hypertonic saline produces a 25.9% reduction (0.94 days) in mean length of hospital stay vs. nebulized normal saline in hospitalized infants No adverse side affects Nebulized hypertonic saline + bronchodilators should be considered effective & safe treatment for infants with viral bronchiolitis

What is Ribavirin?
Guanosine analogue with broad spectrum antiviral activity Approved by FDA in 1985 Approved for use in nebulized form in infants & children with RSV VERY expensive Potentially teratogenic in pregnant caregivers

Reviewing the Evidence: Ribavirin

A recent Cochrane review of RCT comparing Ribavirin to placebo
Decrease in mortality rate was not statistically significant Decrease in risk of respiratory deterioration was not statistically significant Decrease in hospital days was not statistically significant Decrease in ventilator days was not statistically significant

What does the evidence show for antibiotics? Several retrospective studies indentified low rates of SBI (0-3.7%) in patients with bronchiolitis and/or infections with RSV
More likely to be UTI than bacteremia or meningitis 2396 infants with RSV bronchiolitis,
39 patients with SBI (1.6 %) 69% of the 39 patients with SBI had a UTI

What does the evidence show for antibiotics? Prospective studies of SBI in bronchiolitis and/or RSV infections also show low rates (1-12%)
Infants < 28 days, risk of SBI 10.1% in RSV + vs 14.2% in RSV Infants 29-60 days RSV +, all SBIs were UTIs Infants 29-60 days, rate of UTI 5.5% in RSV+ vs 11.7% in RSV -

The Role of Antibiotics

AAP Clinical Practice Guideline
Antibiotics medications should be used only in children with bronchiolitis who have specific indications of the coexistence of a bacterial infection. When present, bacterial infection should be treated in the same manner as in the absence of bronchiolitis

The Role of Supplemental O2

AAP Clinical Practice Guideline
Supplemental oxygen is indicated if oxyhemoglobin saturation (SpO2) falls persistently < 90% in previously healthy infants. As the childs clinical course improves, continuous measurement of SpO2 is not routinely needed. Infants with a known history of hemodynamically significant heart of lung disease and premature infants require close monitoring as the oxygen is weaned.

Hydration Status
AAP Clinical Practice Guideline
Clinicians should assess hydration & ability to take fluids orally

The Role of Chest Physiotherapy

AAP Clinical Practice Guideline
Chest physiotherapy should not be used routinely in the management of bronchiolitis

The Role of Suctioning

Common practice at CMH No evidence to support the benefit of suctioning

Reasons to Suction
Inability to cough effectively WITH one of the following:
Oxygen requirement Increased RR Increased WOB (retractions, head bobbing, nasal flaring)

Retention of secretions WITH one of the following:

Oxygen requirement Increased RR Increased WOB (retractions, head bobbing, nasal flaring)

Suctioning Quick Tips

Nasal Aspiration
First line of defense, try this before nasopharyngeal suctioning Common practice at CMH is to use saline
No evidence to support or disprove the use of saline in nasal suctioning

Adverse Effects of Suctioning

Mucosal trauma Hypoxia Emotional distress to parent or child Atelectasis Discomfort Tachycardia Apnea Increased bronchospasm Vagal stimulation Increased blood pressure Pneumothorax Increased Intracranial pressure

Summary of the Evidence

Bronchiolitis is primarily a clinical diagnosis Treatment is primarily supportive care & includes oxygen, suctioning and if necessary intubation and mechanical ventilation Clinicians should not routinely order labs & x-rays
X-rays may be useful when the hospitalized patient does not improve as expected

Bronchodilators should not be used routinely in the treatment of bronchiolitis

It may be reasonable to administer a nebulized bronchodilator & evaluate clinical response Racemic epinephrine may be beneficial

Evidence does not support the use of steroids Antibiotics should only be used to treat coexisting bacterial infections

Shortfalls in Care: Variation in Care

Significant practice variation & resource over-utilization exits Antibiotic use in US ED estimated 37-53%
Resistant bacteria Unnecessary cost

Short acting B-agonist use 53% Systemic steroids use 13% Use of ineffective therapies: anticholinergics, theophylline & OTC decongestants CXR use 46-72%

References
American Academy of Pediatrics. Bronchiolitis. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006; 560-566. American Academy of Pediatrics, Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and Management of Bronchiolitis. Pediatrics. 2006; 118:1774-1793. Bordley WC, Viswanathan M, King V, et al. Diagnosis and testing in bronchiolitis: A systematic review. Arch Pediatr Adolesc Med. 2004; 158:119-126. Childrens Mercy Hospital & Clinics Clinical Practice Guidelines for Bronchiolitis.

References
Center for Disease Control & Prevention website @ www.cdc.gov, National Center for Infectious Diseases, Respiratory and Enteric Viruses Branch. The Cochrane Collaboration, Cochrane Reviews @ www.cochrane.org. Colditz PB, Henry RL, DeSilva LM. Apnoea and bronchiolitis due to respiratory syncytial virus. Aust Paediatr J 1982; 18:53-54. Corneli HM, Mahajan P, Shaw KN, Zorc JJ, Kuppermann N. Oral Dexamethasone in Bronchiolitis: A Multicenter Randomized Controlled Trial. Abstract in Pediatr Emerg Care. 2006; 22:683. Goodman D. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Text Book of Pediatrics. 17th ed. Philadelphia, PA: Saunders; 2004; 1415-1417.

References
Kneyber MC, Brandenburg AH, de Groot R, Joosten KF, Rothbarth PH, Ott A, Moll HA. Risk factors for respiratory synctial virus associated apnoea. Eur J Pediatr. 1998. 157:331-5. Kupperman N, Bank DE, Walton EA, Senac MO, McCaslin I. Risks for bacteremia and urinary tract infections in young febrile children with bronchiolitis. Arch Pediatr Adolesc Med. 1997. 151:1207-1214. Levine DA, Platt SL, Dayan PS, et. al. Risk of serious bacterial infection in young febrile infants with respiratory synctial virus infections. Pediatrics. 2004. 113:1728-1734. Willwerth BM, Harper MB, Greenes DS. Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea. Ann Emerg Med. 2006. 48:441-7.