Guidance for the Clinician in Rendering Pediatric Care

CLINICAL PRACTICE GUIDELINE Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis

Shawn L. Ralston, MD, FAAP, Allan S. Lieberthal, MD, FAAP, abstract H. Cody Meissner, MD, FAAP, Brian K. Alverson, MD, FAAP, Jill E. This guideline is a revision of the clinical practice guideline, “Diagnosis Baley, MD, FAAP, Anne M. Gadomski, MD, MPH, FAAP, ” David W. Johnson, MD, FAAP, Michael J. Light, MD, FAAP, and Management of Bronchiolitis, published by the American Academy Nizar F. Maraqa, MD, FAAP, Eneida A. Mendonca, MD, PhD, of Pediatrics in 2006. The guideline applies to children from 1 through FAAP, FACMI, Kieran J. Phelan, MD, MSc, Joseph J. Zorc, MD, 23 months of age. Other exclusions are noted. Each key action state- MSCE, FAAP, Danette Stanko-Lopp, MA, MPH, Mark A. ment indicates level of evidence, benefit-harm relationship, and level Brown, MD, Ian Nathanson, MD, FAAP, Elizabeth of recommendation. Key action statements are as follows: Pediatrics Rosenblum, MD, Stephen Sayles III, MD, FACEP, and Sinsi Hernandez-Cancio, JD 2014;134:e1474–e1502 KEY WORDS bronchiolitis, infants, children, respiratory syncytial virus, evidence-based, guideline DIAGNOSIS ABBREVIATIONS AAP—American Academy of Pediatrics 1a. Clinicians should diagnose bronchiolitis and assess disease se- AOM—acute otitis media verity on the basis of history and physical examination (Evidence CI—confidence interval Quality: B; Recommendation Strength: Strong Recommendation). ED—emergency department KAS—Key Action Statement 1b. Clinicians should assess risk factors for severe disease, such as LOS—length of stay age less than 12 weeks, a history of prematurity, underlying car- MD—mean difference diopulmonary disease, or immunodeficiency, when making decisions PCR—polymerase chain reaction — about evaluation and management of children with bronchiolitis RSV respiratory syncytial virus SBI—serious bacterial infection (Evidence Quality: B; Recommendation Strength: Moderate Rec- This document is copyrighted and is property of the American ommendation). Academy of Pediatrics and its Board of Directors. All authors have 1c. When clinicians diagnose bronchiolitis on the basis of history and filed conflict of interest statements with the American Academy of physical examination, radiographic or laboratory studies should Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of not be obtained routinely (Evidence Quality: B; Recommendation Pediatrics has neither solicited nor accepted any commercial Strength: Moderate Recommendation). involvement in the development of the content of this publication. The recommendations in this report do not indicate an exclusive TREATMENT course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. 2. Clinicians should not administer albuterol (or salbutamol) to in- All clinical practice guidelines from the American Academy of fants and children with a diagnosis of bronchiolitis (Evidence Qual- Pediatrics automatically expire 5 years after publication unless ity: B; Recommendation Strength: Strong Recommendation). reaffirmed, revised, or retired at or before that time. 3. Clinicians should not administer epinephrine to infants and children Dedicated to the memory of Dr Caroline Breese Hall. with a diagnosis of bronchiolitis (Evidence Quality: B; Recommen- dation Strength: Strong Recommendation). www.pediatrics.org/cgi/doi/10.1542/peds.2014-2742 4a. Nebulized hypertonic saline should not be administered to in- doi:10.1542/peds.2014-2742 fants with a diagnosis of bronchiolitis in the emergency depart- ment (Evidence Quality: B; Recommendation Strength: Moderate PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Recommendation). Copyright © 2014 by the American Academy of Pediatrics 4b. Clinicians may administer nebulized hypertonic saline to infants and children hospitalized for bronchiolitis (Evidence Quality: B; Recommendation Strength: Weak Recommendation [based on ran- domized controlled trials with inconsistent findings]).

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5. Clinicians should not administer 29 weeks, 0 days or greater 12b. Clinicians should counsel care- systemic corticosteroids to infants (Evidence Quality: B; Recom- givers about exposing the in- with a diagnosis of bronchiolitis in mendation Strength: Strong fant or child to environmental any setting (Evidence Quality: A; Rec- Recommendation). tobacco smoke and smoking ommendation Strength: Strong Rec- 10b. Clinicians should administer cessation when assessing a ommendation). palivizumab during the first child for bronchiolitis (Evidence 6a. Clinicians may choose not to ad- year of life to infants with he- Quality: B; Recommendation minister supplemental oxygen if modynamically significant heart Strength: Strong). the oxyhemoglobin saturation ex- disease or chronic lung disease 13. Clinicians should encourage ex- ceeds 90% in infants and children of prematurity defined as pre- clusive breastfeeding for at least with a diagnosis of bronchiolitis term infants <32 weeks 0 days’ 6 months to decrease the mor- (Evidence Quality: D; Recommen- gestation who require >21% bidity of respiratory infections. dation Strength: Weak Recommen- oxygen for at least the first (Evidence Quality: B; Recommen- dation [based on low level evidence 28 days of life (Evidence Quality: dation Strength: Moderate Rec- and reasoning from first princi- B; Recommendation Strength: ommendation). ples]). Moderate Recommendation). 14. Clinicians and nurses should ed- 6b. Clinicians may choose not to use 10c. Clinicians should administer ucate personnel and family mem- continuous pulse oximetry for in- a maximum 5 monthly doses bers on evidence-based diagnosis, fants and children with a diagnosis (15 mg/kg/dose) of palivizumab treatment, and prevention in bron- of bronchiolitis (Evidence Quality: during the respiratory syncytial chiolitis. (Evidence Quality: C; obser- D; Recommendation Strength: Weak virus season to infants who vational studies; Recommendation Recommendation [based on low- qualify for palivizumab in the Strength: Moderate Recommenda- level evidence and reasoning from first year of life (Evidence Quality: tion). first principles]). B; Recommendation Strength: 7. Clinicians should not use chest Moderate Recommendation). INTRODUCTION physiotherapy for infants and chil- 11a. All people should disinfect hands dren with a diagnosis of bron- before and after direct contact In October 2006, the American Acad- chiolitis (Evidence Quality: B; with patients, after contact with emy of Pediatrics (AAP) published the Recommendation Strength: Mod- inanimate objects in the direct clinical practice guideline “Diagnosis erate Recommendation). vicinity of the patient, and after and Management of Bronchiolitis.”1 8. Clinicians should not administer removing gloves (Evidence Qual- The guideline offered recommendations antibacterial medications to in- ity: B; Recommendation Strength: ranked according to level of evidence fants and children with a diagno- Strong Recommendation). and the benefit-harm relationship. Since sis of bronchiolitis unless there 11b. All people should use alcohol- completion of the original evidence re- is a concomitant bacterial infec- based rubs for hand decontam- view in July 2004, a significant body of tion, or a strong suspicion of one ination when caring for children literature on bronchiolitis has been (Evidence Quality: B; Recommen- with bronchiolitis. When alcohol- published. This update of the 2006 AAP dation Strength: Strong Recom- based rubs are not available, bronchiolitis guideline evaluates pub- mendation). individuals should wash their lished evidence, including that used in 9. Clinicians should administer naso- hands with soap and water the 2006 guideline as well as evidence gastric or intravenous fluids for (Evidence Quality: B; Recom- published since 2004. Key action state- infants with a diagnosis of bron- mendation Strength: Strong ments (KASs) based on that evidence chiolitis who cannot maintain hy- Recommendation). are provided. dration orally (Evidence Quality: X; 12a. Clinicians should inquire about The goal of this guideline is to provide Recommendation Strength: Strong the exposure of the infant or an evidence-based approach to the di- Recommendation). child to tobacco smoke when agnosis, management, and prevention assessing infants and chil- of bronchiolitis in children from 1 month PREVENTION dren for bronchiolitis (Evidence through 23 months of age. The guideline 10a. Clinicians should not administer Quality: C; Recommendation is intended for pediatricians, family palivizumab to otherwise healthy Strength: Moderate Recom- physicians, emergency medicine spe- infants with a gestational age of mendation). cialists, hospitalists, nurse practitioners,

PEDIATRICS Volume 134, Number 5, November 2014 e1475 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 and physician assistants who care for pneumovirus, influenza, adenovirus, average RSV hospitalization rate was these children. The guideline does not coronavirus, human, and parainflu- 5.2 per 1000 children younger than 24 apply to children with immunodeficien- enza viruses. In a study of inpatients months of age during the 5-year pe- cies, including those with HIV infection and outpatients with bronchiolitis,9 riod between 2000 and 2005.11 The or recipients of solid organ or hema- 76% of patients had RSV, 39% had highest age-specific rate of RSV hos- topoietic stem cell transplants. Children human rhinovirus, 10% had influenza, pitalization occurred among infants with underlying respiratory illnesses, 2% had coronavirus, 3% had human between 30 days and 60 days of age such as recurrent wheezing, chronic metapneumovirus, and 1% had para- (25.9 per 1000 children). For preterm neonatal lung disease (also known as influenza viruses (some patients had infants (<37 weeks’ gestation), the bronchopulmonary dysplasia), neuro- coinfections, so the total is greater than RSV hospitalization rate was 4.6 per muscular disease, or cystic fibrosis and 100%). 1000 children, a number similar to those with hemodynamically significant Bronchiolitis is the most common cause the RSV hospitalization rate for term congenital heart disease are excluded of hospitalization among infants during infants of 5.2 per 1000. Infants born from the sections on management un- the first 12 months of life. Approximately at <30 weeks’ gestation had the less otherwise noted but are included in 100 000 bronchiolitis admissions occur highest hospitalization rate at 18.7 the discussion of prevention. This guide- annually in the United States at an children per 1000, although the small line will not address long-term sequelae estimated cost of $1.73 billion.10 One number of infants born before 30 of bronchiolitis, such as recurrent prospective, population-based study weeks’ gestation make this number wheezing or risk of asthma, which is sponsored by the Centers for Disease unreliable. Other studies indicate the a field with a large and distinct lit- Control and Prevention reported the RSV hospitalization rate in extremely erature. Bronchiolitis is a disorder commonly caused by viral lower respiratory tract infection in infants. Bronchiolitis is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways, and increased mucus production. Signs and symp- toms typically begin with rhinitis and cough, which may progress to tachy- pnea, wheezing, rales, use of accessory muscles, and/or nasal flaring.2 Many viruses that infect the respiratory system cause a similar constellation of signs and symptoms. The most com- mon etiology of bronchiolitis is re- spiratory syncytial virus (RSV), with the highest incidence of infection occurring between December and March in North America; however, regional variations occur3 (Fig 1).4 Ninety percent of chil- dren are infected with RSV in the first 2 years of life,5 andupto40%will experience lower respiratory tract in- fection during the initial infection.6,7 Infection with RSV does not grant per- manent or long-term immunity, with reinfections common throughout life.8 FIGURE 1 Other viruses that cause bronchiolitis RSV season by US regions. Centers for Disease Control and Prevention. RSV activity—United States, include human rhinovirus, human meta- July 2011–Jan 2013. MMWR Morb Mortal Wkly Rep. 2013;62(8):141–144.

e1476 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 FROM THE AMERICAN ACADEMY OF PEDIATRICS preterm infants is similar to that of view encompasses the period from of Family Physicians, and American term infants.12,13 2004 through May 2014. College of Emergency Physicians; other The evidence-based approach to guide- outside organizations; and other in- METHODS line development requires that the evi- dividuals identified by the subcom- dence in support of a policy be identified, mittee as experts in the field. The In June 2013, the AAP convened a new appraised, and summarized and that an resulting comments were reviewed subcommittee to review and revise the explicit link between evidence and rec- by the subcommittee and, when ap- 2006 bronchiolitis guideline. The sub- ommendations be defined. Evidence- propriate, incorporated into the guide- committee included primary care physi- based recommendations reflect the line. cians, including general pediatricians, quality of evidence and the balance of This clinical practice guideline is not a family physician, and pediatric sub- benefit and harm that is anticipated intended as a sole source of guidance specialists, including hospitalists, pul- when the recommendation is followed. in the management of children with monologists, emergency physicians, a The AAP policy statement “Classify- bronchiolitis. Rather, it is intended to neonatologist, and pediatric infectious ing Recommendations for Clinical assist clinicians in decision-making. disease physicians. The subcommit- Practice”14 was followed in designat- It is not intended to replace clinical tee also included an epidemiologist ing levels of recommendation (Fig 2; judgment or establish a protocol for trained in systematic reviews, a guide- Table 1). the care of all children with bronchi- line methodologist/informatician, and a olitis. These recommendations may not parent representative. All panel mem- A draft version of this clinical practice provide the only appropriate approach bers reviewed the AAP Policy on Conflict guideline underwent extensive peer to the management of children with of Interest and Voluntary Disclosure and review by committees, councils, and bronchiolitis. were given an opportunity to declare any sections within AAP; the American potential conflicts. Any conflicts can be Thoracic Society, American College of All AAP guidelines are reviewed every found in the author listing at the end of Chest Physicians, American Academy 5 years. this guideline. All funding was provided by the AAP, with travel assistance from the American Academy of Family Phy- sicians, the American College of Chest Physicians, the American Thoracic Society, and the American College of Emergency Physicians for their liaisons. The evidence search and review included electronic database searches in The Cochrane Library, Medline via Ovid, and CINAHL via EBSCO. The search strategy is shown in the Appendix. Re- lated article searches were conducted in PubMed. The bibliographies of arti- cles identified by database searches were also reviewed by 1 of 4 members of the committee, and references iden- tified in this manner were added to the review. Articles included in the 2003 evidence report on bronchiolitis in preparation of the AAP 2006 guide- line2 also were reviewed. In addition, the committee reviewed articles pub- lished after completion of the sys- FIGURE 2 Integrating evidence quality appraisal with an assessment of the anticipated balance between benefits tematic review for these updated and harms leads to designation of a policy as a strong recommendation, moderate recommendation, guidelines. The current literature re- or weak recommendation.

PEDIATRICS Volume 134, Number 5, November 2014 e1477 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 TABLE 1 Guideline Definitions for Evidence-Based Statements Statement Definition Implication Strong recommendation A particular action is favored because anticipated benefits Clinicians should follow a strong recommendation unless clearly exceed harms (or vice versa), and quality of evidence a clear and compelling rationale for an alternative approach is excellent or unobtainable. is present. Moderate recommendation A particular action is favored because anticipated benefits Clinicians would be prudent to follow a moderate clearly exceed harms (or vice versa), and the quality of recommendation but should remain alert to new evidence is good but not excellent (or is unobtainable). information and sensitive to patient preferences. Weak recommendation (based on A particular action is favored because anticipated benefits Clinicians would be prudent to follow a weak recommendation low-quality evidence clearly exceed harms (or vice versa), but the quality of but should remain alert to new information and very evidence is weak. sensitive to patient preferences. Weak recommendation (based on Weak recommendation is provided when the aggregate Clinicians should consider the options in their decision making, balance of benefits and harms) database shows evidence of both benefit and harm that but patient preference may have a substantial role. appear similar in magnitude for any available courses of action

DIAGNOSIS uation and management of children Action Statement Profile KAS 1b Key Action Statement 1a with bronchiolitis (Evidence Quality: Aggregate B B; Recommendation Strength: Mod- evidence Clinicians should diagnose bronchi- erate Recommendation). quality olitis and assess disease severity Benefits Decreased radiation on the basis of history and physical exposure, noninvasive Action Statement Profile KAS 1b (less procedure-associated examination (Evidence Quality: B; discomfort), decreased Aggregate B Recommendation Strength: Strong antibiotic use, cost savings, evidence time saving Recommendation). quality Risk, harm, cost Misdiagnosis, missed Benefits Improved ability to predict diagnosis of comorbid course of illness, Action Statement Profile KAS 1a condition appropriate disposition Benefit-harm Benefits outweigh harms Risk, harm, cost Possible unnecessary Aggregate evidence B assessment hospitalization parental quality Value judgments None anxiety Benefits Inexpensive, Intentional None Benefit-harm Benefits outweigh harms noninvasive, accurate vagueness assessment Risk, harm, cost Missing other Role of patient None Value judgments None diagnoses preferences Intentional “Assess” is not defined Benefit-harm Benefits outweigh Exclusions Infants and children with vagueness assessment harms unexpected worsening Role of patient None Value judgments None disease preferences Intentional vagueness None Strength Moderate recommendation Exclusions None Role of patient None Differences of None Strength Moderate recommendation preferences opinion Exclusions None Differences of None Strength Strong recommendation opinion Differences of opinion None The main goals in the history and physical examination of infants pre- Key Action Statement 1c senting with wheeze or other lower Key Action Statement 1b When clinicians diagnose bronchi- respiratory tract symptoms, particularly Clinicians should assess risk fac- olitis on the basis of history and in the winter season, is to differentiate tors for severe disease, such as physical examination, radiographic infants with probable viral bronchiolitis age <12 weeks, a history of pre- or laboratory studies should not be from those with other disorders. In ad- maturity, underlying cardiopulmo- obtained routinely (Evidence Qual- dition, an estimate of disease severity nary disease, or immunodeficiency, ity: B; Recommendation Strength: (increased respiratory rate, retractions, when making decisions about eval- Moderate Recommendation). decreased oxygen saturation) should

e1478 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 FROM THE AMERICAN ACADEMY OF PEDIATRICS be made. Most clinicians recognize rate in otherwise healthy children suggesting that it reliably detects hyp- bronchiolitis as a constellation of clin- changes considerably over the first oxemia not suspected on physical ical signs and symptoms occurring in year of life.22–25 In hospitalized children, examination36,40; however, few studies children younger than 2 years, includ- the 50th percentile for respiratory rate have assessed the effectiveness of ing a viral upper respiratory tract decreased from 41 at 0 to 3 months of pulse oximetry to predict clinical out- prodrome followed by increased re- age to 31 at 12 to 18 months of age.26 comes. Among inpatients, perceived spiratory effort and wheezing. Clinical Counting respiratory rate over the need for supplemental oxygen on the signs and symptoms of bronchiolitis course of 1 minute is more accurate basis of pulse oximetry has been as- consist of rhinorrhea, cough, tachypnea, than shorter observations.27 The pres- sociated with prolonged hospitaliza- wheezing, rales, and increased respi- ence of a normal respiratory rate tion, ICU admission, and mechanical ratory effort manifested as grunting, suggests that risk of significant viral ventilation.16,34,41 Among outpatients, nasal flaring, and intercostal and/or or bacterial lower respiratory tract available evidence differs on whether subcostal retractions. infection or pneumonia in an infant is mild reductions in pulse oximetry (<95% The course of bronchiolitis is variable low (negative likelihood ratio approxi- on room air) predict progression of and dynamic, ranging from transient mately 0.5),27–29 but the presence of disease or need for a return obser- events,suchasapnea,toprogressive tachypnea does not distinguish be- vational visit.38 respiratory distress from lower airway tween viral and bacterial disease.30,31 Apnea has been reported to occur with obstruction. Important issues to assess The evidence relating the presence of a wide range of prevalence estimates in the history include the effects of re- specific findings in the assessment of and viral etiologies.42,43 Retrospective, spiratory symptoms on mental status, bronchiolitis to clinical outcomes is hospital-based studies have included feeding, and hydration. The clinician limited. Most studies addressing this a high proportion of infants with risk should assess the ability of the family issue have enrolled children when factors, such as prematurity or neuro- to care for the child and to return for presenting to hospital settings, in- muscular disease, that may have biased further evaluation if needed. History cluding a large, prospective, multicen- the prevalence estimates. One large of underlying conditions, such as pre- ter study that assessed a variety of study found no apnea events for infants maturity, cardiac disease, chronic outcomes from the emergency de- assessed as low risk by using several pulmonary disease, immunodeficiency, partment (ED) and varied inpatient risk factors: age >1 month for full-term or episodes of previous wheezing, should settings.18,32,33 Severe adverse events, infants or 48 weeks’ postconceptional be identified. Underlying conditions that such as ICU admission and need for age for preterm infants, and absence may be associated with an increased mechanical ventilation, are uncommon of any previous apneic event at pre- risk of progression to severe disease among children with bronchiolitis and sentation to the hospital.44 Another or mortality include hemodynamically limit the power of these studies large multicenter study found no asso- significant congenital heart disease, to detect clinically important risk fac- ciation between the specific viral agent chronic lung disease (bronchopulmonary tors associated with disease pro- and risk of apnea in bronchiolitis.42 dysplasia), congenital anomalies,15–17 gression.16,34,35 Tachypnea, defined as The literature on viral testing for bron- in utero smoke exposure,18 and the a respiratory rate ≥70 per minute, has chiolitis has expanded in recent years presence of an immunocompromising been associated with increased risk of with the availability of sensitive poly- state.19,20 In addition, genetic abnormal- severe disease in some studies35–37 but merase chain reaction (PCR) assays. ities have been associated with more not others.38 Many scoring systems Large studies of infants hospitalized for severe presentation with bronchiolitis.21 have been developed in an attempt to bronchiolitis have consistently found Assessment of a child with bronchiolitis, objectively quantify respiratory dis- that 60% to 75% have positive test results including the physical examination, can tress, although none has achieved for RSV, and have noted coinfections be complicated by variability in the dis- widespread acceptance and few have in up to one-third of infants.32,33,45 ease state and may require serial demonstrated any predictive validity, In the event an infant receiving observations over time to fully assess the likely because of the substantial tem- monthly prophylaxis is hospitalized child’s status. Upper airway obstruction poral variability in physical findings in with bronchiolitis, testing should be contributes to work of breathing. Suc- infants with bronchiolitis.39 performed to determine if RSV is the tioning and positioning may decrease Pulse oximetry has been rapidly adopted etiologic agent. If a breakthrough RSV theworkofbreathingandimprovethe into clinical assessment of children infection is determined to be present quality of the examination. Respiratory with bronchiolitis on the basis of data based on antigen detection or other

PEDIATRICS Volume 134, Number 5, November 2014 e1479 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 assay, monthly palivizumab prophylaxis and children with a diagnosis of A recently updated Cochrane system- should be discontinued because of the bronchiolitis (Evidence Quality: B; atic review assessing the impact of very low likelihood of a second RSV Recommendation Strength: Strong bronchodilators on oxygen saturation, infection in the same year. Apart from Recommendation). the primary outcome measure, reported this setting, routine virologic testing is 30 randomized controlled trials in- not recommended. Action Statement Profile KAS 2 volving 1992 infants in 12 countries.56 Infants with non-RSV bronchiolitis, in Aggregate B Some studies included in this review particular human rhinovirus, appear to evidence evaluated agents other than albuterol/ quality salbutamol (eg, ipratropium and meta- have a shorter courses and may rep- Benefits Avoid adverse effects, avoid resent a different phenotype associated ongoing use of ineffective proterenol) but did not include epi- 32 medication, lower costs nephrine. Small sample sizes, lack of with repeated wheezing. PCR assay fi Risk, harm, cost Missing transient bene tof standardized methods for outcome results should be interpreted cautiously, drug given that the assay may detect pro- Benefit-harm Benefits outweigh harms evaluation (eg, timing of assessments), longed viral shedding from an unrelated assessment and lack of standardized intervention Value judgments Overall ineffectiveness (various bronchodilators, drug dosages, previous illness, particularly with rhi- outweighs possible novirus. In contrast, RSV detected by transient benefit routes of administration, and nebuliza- PCR assay almost always is associated Intentional None tion delivery systems) limit the in- vagueness terpretation of these studies. Because with disease. At the individual patient Role of patient None level, the value of identifying a spe- preferences of variable study designs as well as the cific viral etiology causing bronchi- Exclusions None inclusion of infants who had a history of Strength Strong recommendation 33 previous wheezing in some studies, olitis has not been demonstrated. Differences of None Current evidence does not support opinion there was considerable heterogeneity routine chest radiography in children Notes This guideline no longer in the studies. Sensitivity analysis (ie, recommends a trial of with bronchiolitis. Although many including only studies at low risk of albuterol, as was considered fi infants with bronchiolitis have abnor- in the 2006 AAP bronchiolitis bias) signi cantly reduced heterogene- malities on chest radiography, data guideline ity measures for oximetry while having are insufficient to demonstrate that little effect on the overall effect size of – chest radiography correlates well with oximetry (mean difference [MD] 0.38, 95% confidence interval [CI] –0.75 to disease severity. Atelectasis on chest Although several studies and reviews 0.00). Those studies showing benefit57–59 radiography was associated with in- have evaluated the use of bronchodi- are methodologically weaker than other creased risk of severe disease in 1 lator medications for viral bronchiolitis, studies and include older children with outpatient study.16 Further studies, in- most randomized controlled trials have recurrent wheezing. Results of the cluding 1 randomized trial, suggest failed to demonstrate a consistent ben- Cochrane review indicated no benefitin children with suspected lower respi- efitfromα-orβ-adrenergic agents. theclinicalcourseofinfantswith ratory tract infection who had radiog- Several meta-analyses and systematic bronchiolitis who received bronchodi- raphy performed were more likely to reviews48–53 have shown that broncho- receive antibiotics without any differ- dilators may improve clinical symptom lators. The potential adverse effects ence in outcomes.46,47 Initial radiography scores, but they do not affect disease (tachycardia and tremors) and cost of should be reserved for cases in which resolution, need for hospitalization, or these agents outweigh any potential fi respiratory effort is severe enough to length of stay (LOS). Because clinical bene ts. warrant ICU admission or where signs scores may vary from one observer to In the previous iteration of this guideline, of an airway complication (such as the next39,54 and do not correlate with a trial of β-agonists was included as pneumothorax) are present. more objective measures, such as pul- an option. However, given the greater monary function tests,55 clinical scores strength of the evidence demonstrat- TREATMENT are not validated measures of the effi- ing no benefit, and that there is no ALBUTEROL cacy of bronchodilators. Although tran- well-established way to determine an sient improvements in clinical score “objective method of response” to Key Action Statement 2 have been observed, most infants bronchodilators in bronchiolitis, this Clinicians should not administer treated with bronchodilators will not option has been removed. Although it albuterol (or salbutamol) to infants benefit from their use. is true that a small subset of children

e1480 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 FROM THE AMERICAN ACADEMY OF PEDIATRICS with bronchiolitis may have reversible EPINEPHRINE analysis by Hartling et al64 systemati- airway obstruction resulting from Key Action Statement 3 cally evaluated the evidence on this smooth muscle constriction, attempts topic and found no evidence for utility Clinicians should not administer to define a subgroup of responders in the inpatient setting. Two large, epinephrine to infants and children have not been successful to date. If multicenter randomized trials com- with a diagnosis of bronchiolitis a clinical trial of bronchodilators is paring nebulized epinephrine to pla- (Evidence Quality: B; Recommenda- 65 66 undertaken, clinicians should note that the cebo or albuterol in the hospital tion Strength: Strong Recommen- setting found no improvement in LOS variability of the disease process, the host’s dation). or other inpatient outcomes. A recent, airway, and the clinical assessments, par- large multicenter trial found a similar ticularly scoring, would limit the clinician’s fi Action Statement Pro le KAS 3 lack of efficacy compared with pla- ability to observe a clinically relevant re- Aggregate B cebo and further demonstrated lon- sponse to bronchodilators. evidence ger LOS when epinephrine was used quality 60 Chavasse et al reviewed the available Benefits Avoiding adverse effects, lower on a fixed schedule compared with an literature on use of β-agonists for chil- costs, avoiding ongoing use as-needed schedule.67 This evidence dren younger than 2 years with re- of ineffective medication suggests epinephrine should not be Risk, harm, cost Missing transient benefitof current wheezing. At the time of that drug used in children hospitalized for bron- review, there were 3 studies in the Benefit-harm Benefits outweigh harms chiolitis, except potentially as a rescue outpatient setting, 2 in the ED, and 3 assessment agent in severe disease, although for- Value judgments The overall ineffectiveness in the pulmonary function laboratory outweighs possible transient mal study is needed before a recom- setting. This review concluded there benefit mendation for the use of epinephrine fi Intentional None in this setting. were no clear bene ts from the use vagueness of β-agonists in this population. The Role of patient None The role of epinephrine in the out- authors noted some conflicting evi- preferences patient setting remains controver- Exclusions Rescue treatment of rapidly sial. A major addition to the evidence dence, but further study was recom- deteriorating patients mended only if the population could be Strength Strong recommendation base came from the Canadian Bron- 68 clearly defined and meaningful out- Differences of None chiolitis Epinephrine Steroid Trial. opinion This multicenter randomized trial come measures could be identified. enrolled 800 patients with bron- The population of children with bron- chiolitis from 8 EDs and compared chiolitis studied in most trials of hospitalization rates over a 7-day Epinephrine is an adrenergic agent bronchodilators limits the ability to period. This study had 4 arms: neb- with both β-andα-receptor agonist make recommendations for all clinical ulized epinephrine plus oral dexa- activity that has been used to treat scenarios. Children with severe disease methasone, nebulized epinephrine upper and lower respiratory tract ill- or with respiratory failure were gen- plus oral placebo, nebulized placebo nesses both as a systemic agent and erally excluded from these trials, and plus oral dexamethasone, and neb- directly into the respiratory tract, this evidence cannot be generalized to ulized placebo plus oral placebo. The where it is typically administered as these situations. Studies using pulmo- a nebulized solution. Nebulized epi- group of patients who received epi- nary function tests show no effect of nephrine has been administered in nephrine concomitantly with corti- albuterol among infants hospitalized the racemic form and as the purified costeroids had a lower likelihood 56,61 with bronchiolitis. One study in L-enantiomer, which is commercially of hospitalization by day 7 than the a critical care setting showed a small available in the United States for in- double placebo group, although this decrease in inspiratory resistance af- travenous use. Studies in other dis- effect was no longer statistically sig- ter albuterol in one group and leval- eases, such as croup, have found no nificant after adjusting for multiple buterol in another group, but therapy difference in efficacy on the basis of comparisons. was accompanied by clinically signifi- preparation,63 although the compari- The systematic review by Hartling cant tachycardia.62 This small clinical son has not been specifically studied et al64 concluded that epinephrine change occurring with significant ad- for bronchiolitis. Most studies have reduced hospitalizations compared verse effects does not justify recom- compared L-epinephrine to placebo or with placebo on the day of the ED visit mending albuterol for routine care. albuterol. A recent Cochrane meta- but not overall. Given that epinephrine

PEDIATRICS Volume 134, Number 5, November 2014 e1481 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 has a transient effect and home ad- Recommendation [based on ran- for the analysis of LOS with an aggregate ministration is not routine practice, domized controlled trials with 1-day decrease reported, a result largely discharging an infant after observing inconsistent findings]). driven by the inclusion of 3 studies with a response in a monitored setting relatively long mean length of stay of 5 to raises concerns for subsequent pro- Action Statement Profile KAS 4b 6 days. The analysis of effect on clinical gression of illness. Studies have not Aggregate B scores included 7 studies involving 640 found a difference in revisit rates, evidence patients in both inpatient and outpatient although the numbers of revisits are quality settings and demonstrated incremental Benefits May shorten hospital stay if LOS small and may not be adequately is >72 h positive effect with each day posttreat- powered for this outcome. In summary, Risk, harm, cost Adverse effects such as ment from day 1 to day 3 (–0.88 MD on the current state of evidence does not wheezing and excess day 1, –1.32 MD on day 2, and –1.51 MD secretions; cost 73 support a routine role for epineph- Benefit-harm Benefits outweigh harms for on day 3). Finally, Zhang et al found no rine for bronchiolitis in outpatients, assessment longer hospital stays effect on hospitalization rates in the although further data may help to Value judgments Anticipating an individual pooled analysis of 1 outpatient and 3 ED fi child’s LOS is difficult. Most better de ne this question. US hospitals report an studies including 380 total patients. average LOS of <72 h for Several randomized trials published after patients with bronchiolitis. the Cochrane review period further in- HYPERTONIC SALINE This weak recommendation applies only if the average formed the current guideline recommen- Key Action Statement 4a length of stay is >72 h dation. Four trials evaluated admission Nebulized hypertonic saline should Intentional This weak recommendation is rates from the ED, 3 using 3% saline and 1 vagueness based on an average LOS and 74–76 76 not be administered to infants with does not address the using 7% saline. A single trial dem- a diagnosis of bronchiolitis in the individual patient. onstrated a difference in admission rates emergency department (Evidence Role of patient None from the ED favoring hypertonic saline, Quality: B; Recommendation Strength: preferences Exclusions None although the other 4 studies were con- Moderate Recommendation). Strength Weak cordant with the studies included in the Differences of None Cochrane review. However, contrary to the fi opinion Action Statement Pro le KAS 4a studies included in the Cochrane review, Aggregate B none of the more recent trials reported evidence improvement in LOS and, when added to quality Nebulized hypertonic saline is an in- Benefits Avoiding adverse effects, such creasingly studied therapy for acute the older studies for an updated meta- as wheezing and excess viral bronchiolitis. Physiologic evidence analysis, they significantly attenuate the secretions, cost summary estimate of the effect on LOS.76,77 Risk, harm, cost None suggests that hypertonic saline in- Benefit-harm Benefits outweigh harms creases mucociliary clearance in both Most of the trials included in the Cochrane assessment normalanddiseasedlungs.69–71 Because review occurred in settings with typical Value judgments None the pathology in bronchiolitis involves LOS of more than 3 days in their usual Intentional None fi vagueness airway inflammation and resultant care arms. Hence, the signi cant decrease Role of patient None mucus plugging, improved mucocili- in LOS noted by Zhang et al73 may not be preferences ary clearance should be beneficial, al- generalizable to the United States where Exclusions None 10 Strength Moderate recommendation though there is only indirect evidence the average LOS is 2.4 days. One other Differences of None to support such an assertion. A more ongoing clinical trial performed in the opinion specific theoretical mechanism of ac- United States, unpublished except in ab- tion has been proposed on the basis of stract form, further supports the obser- the concept of rehydration of the air- vation that hypertonic saline does not way surface liquid, although again, decrease LOS in settings where expected Key Action Statement 4b evidence remains indirect.72 stays are less than 3 days.78 Clinicians may administer nebulized A2013Cochranereview73 included 11 The preponderance of the evidence sug- hypertonic saline to infants and trials involving 1090 infants with mild to gests that 3% saline is safe and effective at children hospitalized for bron- moderate disease in both inpatient and improving symptoms of mild to moderate chiolitis (Evidence Quality: B; Rec- emergency settings. There were 6 studies bronchiolitis after 24 hours of use and ommendation Strength: Weak involving 500 inpatients providing data reducing hospital LOS in settings in which

e1482 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 FROM THE AMERICAN ACADEMY OF PEDIATRICS the duration of stay typically exceeds 3 respiratory diseases, such as asthma why simultaneous administration of days.Ithasnotbeenshowntobeeffective and croup,82–84 the evidence on corti- these drugs could be synergistic.89–92 at reducing hospitalization in emergency costeroid use in bronchiolitis is nega- However, other bronchiolitis trials of settings or in areas where the length tive. The most recent Cochrane corticosteroids administered by us- of usage is brief. It has not been systematic review shows that cortico- ing fixed simultaneous bronchodila- studied in intensive care settings, steroids do not significantly reduce tor regimens have not consistently and most trials have included only outpatient admissions when compared shown benefit93–97;hence,arecommen- patients with mild to moderate dis- with placebo (pooled risk ratio, 0.92; dation regarding the benefitofcom- ease. Most studies have used a 3% 95% CI, 0.78 to 1.08; and risk ratio, 0.86; bined dexamethasone and epinephrine saline concentration, and most have 95% CI, 0.7 to 1.06, respectively) and therapy is premature. combined it with bronchodilators do not reduce LOS for inpatients (MD The systematic review of cortico- with each dose; however, there is –0.18 days; 95% CI –0.39 to 0.04).85 No steroids in children with bronchiolitis retrospective evidence that the rate other comparisons showed relevant cited previously did not find any dif- of adverse events is similar without differences for either primary or sec- ferences in short-term adverse events bronchodilators,79 as well as pro- ondary outcomes. This review con- as compared with placebo.86 However, spective evidence extrapolated from tained 17 trials with 2596 participants corticosteroid therapy may prolong 2 trials without bronchodilators.79,80 and included 2 large ED-based ran- viral shedding in patients with bron- A single study was performed in the domized trials, neither of which showed chiolitis.17 ambulatory outpatient setting81; how- reductions in hospital admissions with In summary, a comprehensive sys- ever, future studies in the United States treatment with corticosteroids as com- tematic review and large multicenter should focus on sustained usage on pared with placebo.69,86 randomized trials provide clear evi- the basis of pattern of effects dis- One of these large trials, the Canadian dence that corticosteroids alone do cerned in the available literature. Bronchiolitis Epinephrine Steroid Trial, not provide significant benefitto however, did show a reduction in hos- children with bronchiolitis. Evidence CORTICOSTEROIDS pitalizations 7 days after treatment with for potential benefit of combined Key Action Statement 5 combined nebulized epinephrine and corticosteroid and agents with both α β Clinicians should not administer oral dexamethasone as compared with -and -agonist activity is at best systemic corticosteroids to infants placebo.69 Although an unadjusted ana- tentative, and additional large trials with a diagnosis of bronchiolitis in lysis showed a relative risk for hospi- are needed to clarify whether this any setting (Evidence Quality: A; talization of 0.65 (95% CI 0.45 to 0.95; therapy is effective. Recommendation Strength: Strong P = .02) for combination therapy as Further, although there is no evidence Recommendation). compared with placebo, adjustment of short-term adverse effects from for multiple comparison rendered the corticosteroid therapy, other than Action Statement Profile KAS 5 result insignificant (P = .07). These prolonged viral shedding, in infants and children with bronchiolitis, there Aggregate A results have generated considerable evidence quality controversy.87 Although there is no is inadequate evidence to be certain Benefits No clinical benefit, avoiding standard recognized rationale for why of safety. adverse effects Risk, harm, cost None combination epinephrine and dexa- fi fi methasone would be synergistic in Bene t-harm Bene ts outweigh harms OXYGEN assessment infants with bronchiolitis, evidence in Value judgments None adults and children older than 6 Key Action Statement 6a Intentional None vagueness years with asthma shows that adding Clinicians may choose not to ad- Role of patient None inhaled long-acting β agonists to minister supplemental oxygen if the preferences moderate/high doses of inhaled cor- Exclusions None oxyhemoglobin saturation exceeds Strength Strong recommendation ticosteroids allows reduction of the 90% in infants and children with a Differences of None corticosteroid dose by, on average, diagnosis of bronchiolitis (Evidence opinion 60%.88 Basic science studies focused Quality: D; Recommendation Strength: on understanding the interaction be- Weak Recommendation [based on Although there is good evidence of tween β agonists and corticosteroids low-level evidence and reasoning benefit from corticosteroids in other have shown potential mechanisms for from first principles]).

PEDIATRICS Volume 134, Number 5, November 2014 e1483 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 Action Statement Profile KAS 6a associated closely with a perceived do not have impaired intellectual abil- 106–108 Benefits Decreased hospitalizations, need for hospitalization in infants with ities or behavioral disturbance. decreased LOS bronchiolitis.98,99 Additionally, oxygen Supplemental oxygen provided for in- Risk, harm, cost Hypoxemia, physiologic stress, saturation has been implicated as prolonged LOS, increased fants not requiring additional re- hospitalizations, increased a primary determinant of LOS in spiratory support is best initiated with LOS, cost bronchiolitis.40,100,101 nasal prongs, although exact mea- fi fi Bene t-harm Bene ts outweigh harms surement of fraction of inspired oxy- assessment Physiologic data based on the oxyhe- Value judgments Oxyhemoglobin saturation moglobin dissociation curve (Fig 3) gen is unreliable with this method.109 >89% is adequate to demonstrate that small increases in Pulse oximetry is a convenient method oxygenate tissues; the risk of hypoxemia with arterial partial pressure of oxygen are to assess the percentage of hemo- oxyhemoglobin saturation associated with marked improvement globin bound by oxygen in children. >89% is minimal in pulse oxygen saturation when the Pulse oximetry has been erroneously Intentional None vagueness latter is less than 90%; with pulse oxy- used in bronchiolitis as a proxy for Role of patient Limited gen saturation readings greater than respiratory distress. Accuracy of pulse preferences 90% it takes very large elevations in oximetry is poor, especially in the 76% Exclusions Children with acidosis or fever to 90% range.110 Further, it has been Strength Weak recommendation (based arterial partial pressure of oxygen to on low-level evidence/ affect further increases. In infants and well demonstrated that oxygen satu- fi reasoning from rst children with bronchiolitis, no data exist ration has much less impact on re- principles) spiratory drive than carbon dioxide Differences of None to suggest such increases result in any 111 opinion clinically significant difference in physi- concentrations in the blood. There is very poor correlation between re- ologic function, patient symptoms, or spiratory distress and oxygen satu- Key Action Statement 6b clinical outcomes. Although it is well rations among infants with lower Clinicians may choose not to use understood that acidosis, temperature, respiratory tract infections.112 Other continuous pulse oximetry for in- and 2,3-diphosphoglutarate influence than cyanosis, no published clinical fants and children with a diagnosis the oxyhemoglobin dissociation curve, sign, model, or score accurately iden- of bronchiolitis (Evidence Quality: there has never been research to tifies hypoxemic children.113 C; Recommendation Strength: Weak demonstrate how those influences Among children admitted for bronchi- Recommendation [based on lower- practically affect infants with hypox- olitis, continuous pulse oximetry mea- level evidence]). emia. The risk of hypoxemia must be surement is not well studied and weighed against the risk of hospitali- fi potentially problematic for children who Action Statement Pro le KAS 6b zation when making any decisions do not require oxygen. Transient desa- Aggregate C about site of care. One study of hospi- turation is a normal phenomenon in evidence talized children with bronchiolitis, for quality healthy infants. In 1 study of 64 healthy Benefits Shorter LOS, decreased alarm example, noted a 10% adverse error or infants between 2 weeks and 6 months fatigue, decreased cost near-miss rate for harm-causing inter- of age, 60% of these infants exhibited Risk, harm, cost Delayed detection of hypoxemia, 103 delay in appropriate weaning ventions. There are no studies on the a transient oxygen desaturation below of oxygen effect of short-term, brief periods of 90%, to values as low as 83%.105 Aret- fi fi Bene t-harm Bene ts outweigh harms hypoxemia such as may be seen in rospective study of the role of continu- assessment Value judgments None bronchiolitis. Transient hypoxemia is ous measurement of oxygenation in Intentional None common in healthy infants.104 Travel of infants hospitalized with bronchiolitis vagueness healthy children even to moderate alti- found that 1 in 4 patients incur unnec- Role of patient Limited preferences tudes of 1300 m results in transient essarily prolonged hospitalization as Exclusions None sleep desaturation to an average of a result of a perceived need for oxygen Strength Weak recommendation (based 84% with no known adverse con- outside of other symptoms40 and no on lower level of evidence) 105 fi Differences of None sequences. Although children with evidence of bene t was found. opinion chronic hypoxemia do incur devel- Pulse oximetry is prone to errors of opmental and behavioral problems, measurement. Families of infants hospi- Although oxygen saturation is a poor children who suffer intermittent hyp- talized with continuous pulse oximeters predictor of respiratory distress, it is oxemia from diseases such as asthma are exposed to frequent alarms that

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continuous positive airway pressure in bronchiolitis.127–130 Clinical evidence suggests it reduces work of breath- ing131,132 and may decrease need for intubation,133–136 although studies are generally retrospective and small. The therapy has been studied in the ED136,137 and the general inpatient setting,134,138 as well as the ICU. The largest and most rigorous retrospective study to date was from Australia,138 which showed a decline in intubation rate in the sub- group of infants with bronchiolitis (n = 330) from 37% to 7% after the intro- duction of high-flow nasal cannula, while the national registry intubation rate remained at 28%. A single pilot for a randomized trial has been pub- FIGURE 3 139 Oxyhemoglobin dissociation curve showing percent saturation of hemoglobin at various partial lished to date. Although promising, pressures of oxygen (reproduced with permission from the educational Web site www.anaesthesiauk. the absence of any completed ran- com).102 domized trial of the efficacy of high-flow nasal cannula in bronchiolitis precludes specific recommendations on it use at may negatively affect sleep. Alarm fa- cluding 2 randomized trials.118,119 Most present. Pneumothorax is a reported tigue is recognized by The Joint of the studies have been performed in complication. Commission as a contributor toward areas of higher altitude, where pro- in-hospital morbidity and mortality.114 longed hypoxemia is a prime deter- One adult study demonstrated very minant of LOS in the hospital.120,121 CHEST PHYSIOTHERAPY poor documentation of hypoxemia al- Readmission rates may be moderately erts by pulse oximetry, an indicator higher in patients discharged with Key Action Statement 7 of alarm fatigue.115 Pulse oximetry home oxygen; however, overall hospital Clinicians should not use chest phys- probes can fall off easily, leading to use may be reduced,122 although not in iotherapy for infants and children inaccurate measurements and alarms.116 all settings.123 Concerns have been with a diagnosis of bronchiolitis (Evi- False reliance on pulse oximetry may raised that home pulse oximetry may dence Quality: B; Recommendation lead to less careful monitoring of re- complicate care or confuse families.124 Strength: Moderate Recommendation). spiratory status. In one study, contin- Communication with follow-up physi- uous pulse oximetry was associated cians is important, because primary Action Statement Profile KAS 7 with increased risk of minor adverse care physicians may have difficulty de- events in infants admitted to a gen- termining safe pulse oximetry levels Aggregate B evidence 117 – 125 eral ward. The pulse oximetry for discontinuation of oxygen. Addi- quality monitored patients were found to tionally, there may be an increased Benefits Decreased stress from have less-effective surveillance of their demand for follow-up outpatient visits therapy, reduced cost Risk, harm, cost None 124 severity of illness when controlling for associated with home oxygen use. Benefit-harm Benefits outweigh harms other variables. Use of humidified, heated, high-flow assessment There are a number of new approaches nasal cannula to deliver air-oxygen Value judgments None Intentional None to oxygen delivery in bronchiolitis, 2 mixtures provides assistance to in- vagueness of which are home oxygen and high- fants with bronchiolitis through mul- Role of patient None frequency nasal cannula. There is tiple proposed mechanisms.126 There preferences fl Exclusions None emerging evidence for the role of home is evidence that high- ow nasal can- Strength Moderate recommendation oxygen in reducing LOS or admission nula improves physiologic measures Differences of None rate for infants with bronchiolitis, in- of respiratory effort and can generate opinion

PEDIATRICS Volume 134, Number 5, November 2014 e1485 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 Airway edema, sloughing of respiratory Quality: B; Recommendation Strength: Enteritis was not evaluated. Urinary tract epithelium into airways, and general- Strong Recommendation). infection occurred at a rate of approxi- ized hyperinflation of the lungs, coupled mately 1%, but asymptomatic bacteri- with poorly developed collateral venti- Action Statement Profile KAS 8 uria may have explained this finding. The lation, put infants with bronchiolitis at Aggregate B authors concluded routine screening for risk for atelectasis. Although lobar at- evidence SBI among hospitalized febrile infants electasis is not characteristic of this quality with bronchiolitis between 30 and 90 fi Bene ts Fewer adverse effects, less fi disease, chest radiographs may show resistance to days of age is not justi ed. Limited data evidence of subsegmental atelectasis, antibacterial agents, suggest the risk of bacterial infection in prompting clinicians to consider or- lower cost hospitalized infants with bronchiolitis dering chest physiotherapy to promote Risk, harm, cost None Benefit-harm Benefits outweigh harms younger than 30 days of age is similar to 140 airway clearance. A Cochrane Review assessment the risk in older infants. An abnormal found 9 randomized controlled trials Value judgments None white blood cell count is not useful for that evaluated chest physiotherapy in Intentional Strong suspicion is not vagueness specifically defined predicting a concurrent SBI in infants hospitalized patients with bronchiolitis. and requires clinician and young children hospitalized with RSV No clinical benefit was found by using judgment. An evaluation lower respiratory tract infection.159 Sev- vibration or percussion (5 trials)141–144 for the source of possible eral retrospective studies support this serious bacterial infection – or passive expiratory techniques (4 tri- should be completed conclusion.160 166 Four prospective stud- – als).145 148 Since that review, a study149 before antibiotic use ies of SBI in patients with bronchiolitis of the passive expiratory technique Role of patient None and/or RSV infections also demonstrated preferences found a small, but significant reduction 167–171 Exclusions None low rates of SBI. in duration of oxygen therapy, but no Strength Strong recommendation Approximately 25% of hospitalized in- other benefits. Differences of None opinion fants with bronchiolitis have radio- Suctioning of the nasopharynx to re- graphic evidence of atelectasis, and it move secretions is a frequent practice may be difficult to distinguish between in infants with bronchiolitis. Although fi Infants with bronchiolitis frequently re- atelectasis and bacterial in ltrate or suctioning the nares may provide ceive antibacterial therapy because of consolidation.169 Bacterial pneumonia temporary relief of nasal congestion fever,152 young age,153 and concern for in infants with bronchiolitis without or upper airway obstruction, a retro- secondary bacterial infection.154 Early consolidation is unusual.170 Antibiotic spective study reported that deep randomized controlled trials155,156 therapy may be justified in some chil- suctioning150 was associated with showed no benefit from routine anti- dren with bronchiolitis who require longer LOS in hospitalized infants 2 bacterial therapy for children with intubation and mechanical ventilation to 12 months of age. The same study bronchiolitis. Nonetheless, antibiotic for respiratory failure.172,173 also noted that lapses of greater therapy continues to be overused in Although acute otitis media (AOM) in than 4 hours in noninvasive, external young infants with bronchiolitis because infants with bronchiolitis may be at- nasal suctioning were also associ- of concern for an undetected bacterial ated with longer LOS. Currently, there tributable to viruses, clinical features infection. Studies have shown that febrile are insufficient data to make a rec- generally do not permit differentiation of infants without an identifiable source of ommendation about suctioning, but viral AOM from those with a bacterial fever have a risk of bacteremia that may 174 it appears that routine use of “deep” component. Two studies address the be as high as 7%. However, a child with suctioning151,153 may not be beneficial. frequency of AOM in patients with a distinct viral syndrome, such as bronchiolitis. Andrade et al175 pro- bronchiolitis, has a lower risk (much spectively identified AOM in 62% of 42 ANTIBACTERIALS less than 1%) of bacterial infection of the patients who presented with bronchi- Key Action Statement 8 cerebrospinal fluid or blood.157 olitis. AOM was present in 50% on entry Clinicians should not administer Ralston et al158 conducted a systematic to the study and developed in an addi- antibacterial medications to infants review of serious bacterial infections tional 12% within 10 days. A subsequent and children with a diagnosis of (SBIs) occurring in hospitalized febrile report176 followed 150 children hospi- bronchiolitis unless there is a con- infants between 30 and 90 days of age talized for bronchiolitis for the de- comitant bacterial infection, or a with bronchiolitis. Instances of bacter- velopment of AOM. Seventy-nine (53%) strong suspicion of one. (Evidence emia or meningitis were extremely rare. developed AOM, two-thirds within the

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first 2 days of hospitalization. AOM did chiolitis. One study found that food in- significant. In a larger open ran- not influence the clinical course or take at less than 50% of normal for the domized trial including infants be- laboratory findings of bronchiolitis. The previous 24 hours is associated with tween 2 and 12 months of age and current AAP guideline on AOM177 rec- a pulse oximetry value of <95%.180 conducted in Australia and New ommends that a diagnosis of AOM Infants with mild respiratory distress Zealand, there were no significant should include bulging of the tympanic may require only observation, particu- differences in rates of admission to membrane. This is based on bulging larly if feeding remains unaffected. ICUs, need for ventilatory support, being the best indicator for the pres- When the respiratory rate exceeds 60 and adverse events between 381 ence of bacteria in multiple tympano- to 70 breaths per minute, feeding may infants assigned to nasogastric hy- centesis studies and on 2 articles be compromised, particularly if nasal dration and 378 infants assigned to comparing antibiotic to placebo ther- secretions are copious. There is limited intravenous hydration.188 There was apy that used a bulging tympanic evidence to suggest coordination of a difference of 4 hours in mean LOS membrane as a necessary part of the breathing with swallowing may be between the intravenous group (82.2 diagnosis.178,179 New studies are needed impaired among infants with bron- hours) and the nasogastric group to determine the incidence of AOM in chiolitis.181 These infants may develop (86.2 hours) that was not statisti- bronchiolitis by using the new criterion increased nasal flaring, retractions, cally significant. The nasogastric of bulging of the tympanic membrane. and prolonged expiratory wheezing route had a higher success rate of Refer to the AOM guideline180 for rec- when fed and may be at increased risk insertion than the intravenous ommendations regarding the manage- of aspiration.182 route. Parental satisfaction scores ment of AOM. One study estimated that one-third of did not differ between the in- infants hospitalized for bronchiolitis travenous and nasogastric groups. NUTRITION AND HYDRATION require fluid replacement.183 One These studies suggest that infants 184 who have difficulty feeding safely Key Action Statement 9 case series and 2 randomized trials,185,186 examined the compara- because of respiratory distress can Clinicians should administer naso- tive efficacy and safety of the in- receive either intravenous or naso- gastric or intravenous fluids for travenous and nasogastric routes gastric fluid replacement; however, infants with a diagnosis of bron- for fluid replacement. A pilot trial more evidence is needed to increase chiolitis who cannot maintain hy- in Israel that included 51 infants the strength of this recommendation. dration orally (Evidence Quality: X; younger than 6 months demon- The possibility of fluid retention re- Recommendation Strength: Strong strated no significant differences in lated to production of antidiuretic Recommendation). the duration of oxygen needed or hormone has been raised in patients time to full oral feeds between with bronchiolitis.187–189 Therefore, Action Statement Profile KAS 9 receipt of hypotonic fluid replace- Aggregate evidence quality X ment and maintenance fluids may Benefits Maintaining hydration increase the risk of iatrogenic hypo- Risk, harm, cost Risk of infection, risk of aspiration with nasogastric tube, discomfort, hyponatremia, intravenous infiltration, overhydration natremia in these infants. A recent Benefit-harm assessment Benefits outweigh harms meta-analysis demonstrated that among Value judgments None hospitalized children requiring main- Intentional vagueness None tenance fluids, the use of hypotonic Role of patient preferences Shared decision as to which mode is used Exclusions None fluids was associated with significant Strength Strong recommendation hyponatremia compared with iso- Differences of opinion None tonic fluids in older children.190 Use of isotonic fluids, in general, appears to be safer.

The level of respiratory distress infants receiving intravenous 5% attributable to bronchiolitis guides dextrose in normal saline solution PREVENTION the indications for fluid replacement. or nasogastric breast milk or for- Conversely, food intake in the previous mula.187 Infants in the intravenous Key Action Statement 10a 24 hours may be a predictor of oxygen group had a shorter LOS (100 vs 120 Clinicians should not administer saturation among infants with bron- hours) but it was not statistically palivizumab to otherwise healthy

PEDIATRICS Volume 134, Number 5, November 2014 e1487 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 infants with a gestational age of 29 Action Statement Profile KAS 10b Palivizumab was licensed by the US weeks, 0 days or greater (Evidence Aggregate evidence quality B Food and Drug Administration in June Quality: B; Recommendation Strength: Benefits Reduced risk of RSV 1998 largely on the basis of results of 1 Strong Recommendation). hospitalization clinical trial.193 The results of a second Risk, harm, cost Injection pain; clinical trial among children with con- increased risk of Action Statement Profile KAS 10a illness from genital heart disease were reported in increased visits to 194 Aggregate evidence B December 2003. No other prospec- clinician office or quality tive, randomized, placebo-controlled clinic; cost; side Benefits Reduced pain of effects from trials have been conducted in any injections, reduced palivizumab subgroup. Since licensure of pal- use of a medication Benefit-harm assessment Benefits outweigh that has shown ivizumab, new peer-reviewed pub- harms minimal benefit, Value judgments None lications provide greater insight into reduced adverse Intentional vagueness None the epidemiology of disease caused by effects, reduced Role of patient preferences Parents may choose 195–197 visits to health care RSV. As a result of new data, the to not accept provider with less Bronchiolitis Guideline Committee and palivizumab exposure to illness Exclusions None the Committee on Infectious Diseases Risk, harm, cost Minimal increase in risk Strength Moderate of RSV hospitalization have updated recommendations for recommendation Benefit-harm assessment Benefits outweigh use of prophylaxis. Differences of opinion None harms Notes This KAS is Value judgments None harmonized with PREMATURITY Intentional vagueness None the AAP policy Role of patient Parents may choose to Monthly palivizumab prophylaxis should statement on preferences not accept palivizumab191,192 be restricted to infants born before 29 palivizumab weeks, 0 days’ gestation, except for Exclusions Infants with chronic lung disease of Key Action Statement 10c infants who qualify on the basis of prematurity and Clinicians should administer a max- congenital heart disease or chronic hemodynamically lung disease of prematurity. Data significant cardiac imum 5 monthly doses (15 mg/kg/ disease (as described dose) of palivizumab during the show that infants born at or after 29 in KAS 10b) RSV season to infants who qualify weeks, 0 days’ gestation have an RSV Strength Recommendation for palivizumab in the first year hospitalization rate similar to the rate Differences of opinion None 11,198 Notes This KAS is harmonized of life (Evidence Quality: B, Recom- of full-term infants. Infants with with the AAP policy mendation Strength: Moderate a gestational age of 28 weeks, 6 days statement on Recommendation). or less who will be younger than 12 palivizumab months at the start of the RSV sea- Action Statement Profile KAS 10c son should receive a maximum of 5

Aggregate evidence quality B Benefits Reduced risk of hospitalization; reduced admission to ICU Risk, harm, cost Injection pain; increased risk of illness from increased visits to clinician office or clinic; cost; adverse effects of palivizumab Benefit-harm assessment Benefits outweigh harms Key Action Statement 10b Value judgments None Intentional vagueness None Clinicians should administer pal- Role of patient preferences None ivizumab during the first year of Exclusions Fewer doses should be used if the bronchiolitis season ends before the life to infants with hemodynami- completion of 5 doses; if the child is hospitalized with a breakthrough RSV, fi monthly prophylaxis should be discontinued cally signi cant heart disease or Strength Moderate recommendation chronic lung disease of prema- Differences of opinion None turity defined as preterm infants Notes This KAS is harmonized with the AAP policy statement on palivizumab191,192 <32 weeks, 0 days’ gestation who require >21% oxygen for at least Detailed evidence to support the policy monthly doses of palivizumab or until the first 28 days of life (Evidence statement on palivizumab and this the end of the RSV season, whichever Quality: B; Recommendation Strength: palivizumab section can be found in the comes first. Depending on the month Moderate Recommendation). technical report on palivizumab.192 of birth, fewer than 5 monthly doses

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Although this CONGENITAL HEART DISEASE dose should be administered in Febru- study was not powered for efficacy, no Despite the large number of subjects ary, and protection will last into March clinically meaningful differences in enrolled, little benefit from pal- for most children. outcome were reported.205 Asurveyof ivizumab prophylaxis was found in cystic fibrosis center directors pub- the industry-sponsored cardiac study SECOND YEAR OF LIFE lished in 2009 noted that palivizumab prophylaxis is not the standard of care among infants in the cyanotic group Because of the low risk of RSV hospi- for patients with cystic fibrosis.206 If (7.9% in control group versus 5.6% in talization in the second year of life, palivizumab group, or 23 fewer hos- a neonate is diagnosed with cystic fi- palivizumab prophylaxis is not recom- brosis by newborn screening, RSV pitalizations per1000 children; P = mended for children in the second year .285).197 In the acyanotic group (11.8% prophylaxis should not be adminis- of life with the following exception. tered if no other indications are pres- vs 5.0%), there were 68 fewer RSV fi Children who satisfy the de nition of ent. A patient with cystic fibrosis with hospitalizations per 1000 prophylaxis chronic lung disease of infancy and recipients (P = .003).197,199,200 clinical evidence of chronic lung dis- continue to require supplemental oxy- ease in the first year of life may be gen, chronic corticosteroid therapy, CHRONIC LUNG DISEASE OF considered for prophylaxis. or diuretic therapy within 6 months PREMATURITY of the onset of the second RSV sea- Palivizumab prophylaxis should be son may be considered for a second Neuromuscular Disease and Pulmonary Abnormality administered to infants and children season of prophylaxis. younger than 12 months who develop The risk of RSV hospitalization is not fi chronic lung disease of prematurity, OTHER CONDITIONS well de nedinchildrenwithpulmonary defined as a requirement for 28 days abnormalities or neuromuscular dis- of more than 21% oxygen beginning Insufficient data are available to rec- ease that impairs ability to clear at birth. If a child meets these cri- ommend routine use of prophylaxis in secretions from the lower airway be- teria and is in the first 24 months of children with Down syndrome, cystic cause of ineffective cough, recurrent life and continues to require sup- fibrosis, pulmonary abnormality, neu- gastroesophageal tract reflux, pulmo- plemental oxygen, diuretic therapy, romuscular disease, or immune com- nary malformations, tracheoesophageal or chronic corticosteroid therapy promise. fistula, upper airway conditions, or within 6 months of the start of the conditions requiring tracheostomy. No RSV season, monthly prophylaxis should Down Syndrome data on the relative risk of RSV hospi- be administered for the remainder of Routine use of prophylaxis for children talization are available for this cohort. the season. in the first year of life with Down Selected infants with disease or con- syndrome is not recommended unless genital anomaly that impairs their NUMBER OF DOSES the child qualifies because of cardiac ability to clear secretions from the disease or prematurity.202 lower airway because of ineffective Community outbreaks of RSV disease cough may be considered for pro- usually begin in November or December, phylaxis during the first year of life. peak in January or February, and end by Cystic Fibrosis late March or, at times, in April.4 Figure 1 Routine use of palivizumab prophylaxis shows the 2011–2012 bronchiolitis sea- in patients with cystic fibrosis is not Immunocompromised Children son, which is typical of most years. recommended.203,204 Available studies Population-based data are not avail- Because 5 monthly doses will provide indicate the incidence of RSV hospital- able on the incidence or severity of RSV more than 24 weeks of protective se- izationinchildrenwithcysticfibrosis hospitalization in children who un- rum palivizumab concentration, admin- is low and unlikely to be different from dergo solid organ or hematopoietic istration of more than 5 monthly doses children without cystic fibrosis. No ev- stem cell transplantation, receive is not recommended within the conti- idence suggests a benefit from pal- chemotherapy, or are immunocom- nental United States. For infants who ivizumab prophylaxis in patients with promised because of other conditions. qualify for 5 monthly doses, initiation of cystic fibrosis. A randomized clinical Prophylaxis may be considered for prophylaxis in November and continua- trial involving 186 children with cystic hematopoietic stem cell transplant

PEDIATRICS Volume 134, Number 5, November 2014 e1489 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 patients who undergo transplantation Key Action Statement 11b caregivers.213 Studies have shown that and are profoundly immunosup- All people should use alcohol-based health care workers have acquired in- 207 pressed during the RSV season. rubs for hand decontamination when fection by performing activities such as caring for children with bronchioli- feeding, diaper change, and playing MISCELLANEOUS ISSUES tis. When alcohol-based rubs are with the RSV-infected infant. Caregivers who had contact only with surfaces Prophylaxis is not recommended for not available, individuals should contaminated with the infants’ secre- prevention of nosocomial RSV disease wash their hands with soap and tions or touched inanimate objects in in the NICU or hospital setting.208,209 water (Evidence Quality: B; Recom- mendation Strength: Strong Rec- patients’ roomsalsoacquiredRSV.In No evidence suggests palivizumab is ommendation). these studies, health care workers a cost-effective measure to prevent contaminated their hands (or gloves) recurrent wheezing in children. Pro- Action Statement Profile KAS 11b with RSV and inoculated their oral or phylaxis should not be administered conjunctival mucosa.214 Frequent hand to reduce recurrent wheezing in later Aggregate evidence quality B fi washing by health care workers has years.210,211 Bene ts Less hand irritation Risk, harm, cost If there is visible been shown to reduce the spread of Monthly prophylaxis in Alaska Native dirt on the RSV in the health care setting.215 children who qualify should be de- hands, hand washing is The Centers for Disease Control and termined by locally generated data necessary; Prevention published an extensive re- regarding season onset and end. alcohol-based view of the hand-hygiene literature and rubs are not Continuation of monthly prophylaxis effective for made recommendations as to indica- for an infant or young child who ex- Clostridium tions for hand washing and hand fi periences breakthrough RSV hospital- dif cile, present 216 fi antisepsis. Among the recom- ization is not recommended. a re hazard, and have a slight mendations are that hands should be increased cost disinfected before and after direct Benefit-harm assessment Benefits outweigh contact with every patient, after con- HAND HYGIENE harms Value judgments None tact with inanimate objects in the di- Key Action Statement 11a Intentional vagueness None rect vicinity of the patient, and before Role of patient preferences None putting on and after removing gloves. All people should disinfect hands Exclusions None If hands are not visibly soiled, an before and after direct contact Strength Strong recommendation alcohol-based rub is preferred. In with patients, after contact with Differences of opinion None guidelines published in 2009, the inanimate objects in the direct vi- cinity of the patient, and after re- World Health Organization also rec- moving gloves (Evidence Quality: B; ommended alcohol-based hand-rubs as the standard for hand hygiene in Recommendation Strength: Strong Efforts should be made to decrease the health care.217 Specifically, systematic Recommendation). spread of RSV and other causative reviews show them to remove organ- agents of bronchiolitis in medical fi isms more effectively, require less Action Statement Pro le KAS 11a settings, especially in the hospital. time, and irritate skin less often than Secretions from infected patients can hand washing with soap or other anti- Aggregate evidence quality B be found on beds, crib railings, ta- Benefits Decreased septic agents and water. The availability bletops, and toys.12 RSV, as well as transmission of bedside alcohol-based solutions in- of disease many other viruses, can survive better creased compliance with hand hygiene Risk, harm, cost Possible hand on hard surfaces than on porous irritation among health care workers.214 fi fi surfaces or hands. It can remain in- Bene t-harm assessment Bene ts outweigh When caring for hospitalized children harms fectious on counter tops for ≥6 hours, Value judgments None with clinically diagnosed bronchioli- Intentional vagueness None on gowns or paper tissues for 20 tis, strict adherence to hand de- Role of patient preferences None to 30 minutes, and on skin for up to contamination and use of personal Exclusions None 20 minutes.212 Strength Strong protective equipment (ie, gloves and recommendation It has been shown that RSV can be carried gowns) can reduce the risk of cross- Differences of opinion None and spread to others on the hands of infection in the health care setting.215

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Other methods of infection control in child to environmental tobacco tis.222–225 The AAP issued a technical viral bronchiolitis include education of smoke and smoking cessation report on the risks of secondhand personnel and family members, surveil- when assessing a child for bron- smoke in 2009. The report makes rec- lance for the onset of RSV season, and chiolitis (Evidence Quality: B; Rec- ommendations regarding effective ways wearing masks when anticipating expo- ommendation Strength: Strong to eliminate or reduce secondhand sure to aerosolized secretions while Recommendation). smoke exposure, including education of performing patient care activities. Pro- parents.226 fi grams that implement the aforemen- Action Statement Pro le KAS 12b Despite our knowledge of this impor- tioned principles, in conjunction with Aggregate evidence quality B tant risk factor, there is evidence to effective hand decontamination and Benefits Reinforces the suggest health care providers identify cohorting of patients, have been shown detrimental fewer than half of children exposed to to reduce the spread of RSV in the effects of smoking, tobacco smoke in the outpatient, in- 218,219 health care setting by 39% to 50%. potential to patient, or ED settings.227–229 Further- decrease more, there is evidence that TOBACCO SMOKE smoking Risk, harm, cost Time to counsel counseling parents in these settings is Key Action Statement 12a Benefit-harm assessment Benefits outweigh well received and has a measurable harms impact. Rosen et al230 performed a Clinicians should inquire about the Value judgments None meta-analysis of the effects of inter- exposure of the infant or child to Intentional vagueness None ventions in pediatric settings on pa- tobacco smoke when assessing Role of patient preferences Parents may choose to ignore rental cessation and found a pooled infants and children for bron- counseling risk ratio of 1.3 for cessation among chiolitis (Evidence Quality: C; Rec- Exclusions None the 18 studies reviewed. ommendation Strength: Moderate Strength Moderate recommendation In contrast to many of the other Recommendation). Differences of opinion None Notes Counseling for recommendations, protecting chil- Action Statement Profile KAS 12a tobacco smoke dren from tobacco exposure is prevention a recommendation that is primarily Aggregate evidence quality C should begin in implemented outside of the clinical Benefits Can identify infants the prenatal and children at period and setting. As such, it is critical that risk whose continue in parents are fully educated about the family may family-centered importance of not allowing smoking benefit from care and at all counseling, well-infant visits in the home and that smoke lingers predicting risk of on clothes and in the environment severe disease for prolonged periods.231 It should Risk, harm, cost Time to inquire Benefit-harm assessment Benefits outweigh be provided in plain language and in a respectful, culturally effective harms Tobacco smoke exposure increases the Value judgments None manner that is family centered, en- risk and severity of bronchiolitis. Stra- Intentional vagueness None gages parents as partners in their Role of patient preferences Parent may choose chan and Cook220 first delineated the child’s health, and factors in their to deny tobacco effects of environmental tobacco smoke use even though literacy, health literacy, and primary on rates of lower respiratory tract dis- they are, in fact, language needs. users ease in infants in a meta-analysis in- Exclusions None cluding 40 studies. In a more recent Strength Moderate 221 recommendation systematic review, Jones et al found BREASTFEEDING Differences of opinion None a pooled odds ratio of 2.51 (95% CI 1.96 to 3.21) for tobacco smoke exposure Key Action Statement 13 and bronchiolitis hospitalization among Clinicians should encourage exclusive the 7 studies specific to the condition. breastfeeding for at least 6 months Other investigators have consistently to decrease the morbidity of respi- Key Action Statement 12b reported tobacco smoke exposure ratory infections (Evidence Quality: Clinicians should counsel care- increases both severity of illness and Grade B; Recommendation Strength: givers about exposing the infant or risk of hospitalization for bronchioli- Moderate Recommendation).

PEDIATRICS Volume 134, Number 5, November 2014 e1491 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 Action Statement Profile KAS 13 with an increased risk for 2 or more Shared decision-making with parents medical visits and hospital admission about diagnosis and treatment of Aggregate evidence quality B Benefits May reduce the risk for wheezing lower respiratory illness. bronchiolitis is a key tenet of patient- of bronchiolitis In Japan, Nishimura et al236 looked centered care. Despite the absence of and other at 3 groups of RSV-positive infants effective therapies for viral bronchi- illnesses; fi multiple benefits de ned as full, partial, or token breast- olitis, caregiver education by clinicians of breastfeeding feeding. There were no significant may have a significant impact on care unrelated to differences in the hospitalization rate patterns in the disease. Children with bronchiolitis Risk, harm, cost None among the 3 groups; however, there bronchiolitis typically suffer from Benefit-harm assessment Benefits outweigh were significant differences in the symptoms for 2 to 3 weeks, and risks duration of hospitalization and the parents often seek care in multiple Value judgments None rate of requiring oxygen therapy, both settings during that time period.237 Intentional vagueness None Role of patient preferences Parents may choose favoring breastfeeding. Given that children with RSV gener- to feed formula ally shed virus for 1 to 2 weeks and rather than from 30% to 70% of family members breastfeed 238,239 Exclusions None FAMILY EDUCATION may become ill, education about Strength Moderate prevention of transmission of disease Key Action Statement 14 recommendation is key. Restriction of visitors to new- Notes Education on Clinicians and nurses should edu- breastfeeding borns during the respiratory virus should begin in cate personnel and family mem- season should be considered. Con- the prenatal bers on evidence-based diagnosis, sistent evidence suggests that pa- period treatment, and prevention in rental education is helpful in the bronchiolitis (Evidence Quality: C; promotion of judicious use of anti- observational studies; Recommen- biotics and that clinicians may mis- In 2012, the AAP presented a general dation Strength; Moderate Recom- interpret parental expectations about policy on breastfeeding.232 The policy mendation). therapy unless the subject is openly statement was based on the proven discussed.240–242 benefits of breastfeeding for at least 6 Action Statement Profile KAS 14 months. Respiratory infections were fi Aggregate evidence quality C shown to be signi cantly less common Benefits Decreased FUTURE RESEARCH NEEDS in breastfed children. A primary re- transmission of  source was a meta-analysis from the disease, benefits Better algorithms for predicting Agency for Healthcare Research and of breastfeeding, the course of illness promotion of  Quality that showed an overall 72% judicious use of Impact of clinical score on patient reduction in the risk of hospitalization antibiotics, risks outcomes secondary to respiratory diseases in of infant lung  damage Evaluating different ethnic groups infants who were exclusively breastfed attributable to and varying response to treat- for 4 or more months compared with tobacco smoke ments those who were formula fed.233 Risk, harm, cost Time to educate properly  Does epinephrine alone reduce ad- The clinical evidence also supports Benefit-harm assessment Benefits outweigh mission in outpatient settings? decreased incidence and severity of harms  Value judgments None Additional studies on epinephrine illness in breastfed infants with bron- Intentional vagueness Personnel is not in combination with dexametha- chiolitis. Dornelles et al234 concluded specifically sone or other corticosteroids that the duration of exclusive breast- defined but  Hypertonic saline studies in the feeding was inversely related to the should include all people who outpatient setting and in in hospi- length of oxygen use and the length of ’ enter a patients tals with shorter LOS hospital stay in previously healthy room infants with acute bronchiolitis. In Role of patient preferences None  More studies on nasogastric hy- Exclusions None dration a large prospective study in Australia, Strength Moderate Oddy et al235 showed that breastfeeding recommendation  More studies on tonicity of intrave- for less than 6 months was associated Differences of opinion None nous fluids

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 Incidence of true AOM in bron- SUBCOMMITTEE ON BRONCHIOLITIS Infectious Diseases Representative (no con- fl chiolitis by using 2013 guideline (OVERSIGHT BY THE COUNCIL ON icts) Eneida A. Mendonca, MD, PhD, FAAP, FACMI: fi QUALITY IMPROVEMENT AND PATIENT de nition SAFETY, 2013–2014) Informatician/Academic Pediatric Intensive  More studies on deep suction- Shawn L. Ralston, MD, FAAP: Chair, Pediatric Care Physician, Partnership for Policy Imple- fl ing and nasopharyngeal suction- Hospitalist (no financial conflicts; published mentation Representative (no con icts) research related to bronchiolitis) Kieran J. Phelan, MD, MSc: General Pedia- ing fl Allan S. Lieberthal, MD, FAAP: Chair, General trician (no con icts)  Strategies for monitoring oxygen Pediatrician with Expertise in Pulmonology (no Joseph J. Zorc, MD, MSCE, FAAP: Pediatric conflicts) Emergency Physician, AAP Section on Emergency saturation fi fl Brian K. Alverson, MD, FAAP: Pediatric Hos- Medicine Representative (no nancial con icts;  Use of home oxygen pitalist, AAP Section on Hospital Medicine published research related to bronchiolitis)  Representative (no conflicts) Danette Stanko-Lopp, MA, MPH: Methodolo- Appropriate cutoff for use of oxy- gist, Epidemiologist (no conflicts) gen in high altitude Jill E. Baley, MD, FAAP: Neonatal-Perinatal Medicine, AAP Committee on Fetus and New- Mark A. Brown, MD: Pediatric Pulmonologist, fl  Oxygen delivered by high-flow na- born Representative (no conflicts) American Thoracic Society Liaison (no con icts) Ian Nathanson, MD, FAAP: Pediatric Pulmo- sal cannula Anne M. Gadomski, MD, MPH, FAAP: General Pediatrician and Research Scientist (no financial nologist, American College of Chest Physicians fl  RSV vaccine and antiviral agents conflicts; published research related to bronchi- Liaison (no con icts) Elizabeth Rosenblum, MD: Academic Family  Use of palivizumab in special olitis including Cochrane review of bronchodilators) David W. Johnson, MD, FAAP: Pediatric Emer- Physician, American Academy of Family Physi- fi fl populations, such as cystic b- gency Medicine Physician (no financial conflicts; cians liaison (no con icts). rosis, neuromuscular diseases, published research related to bronchiolitis) Stephen Sayles, III, MD, FACEP: Emergency Down syndrome, immune defi- Michael J. Light, MD, FAAP: Pediatric Pulmo- Medicine Physician, American College of Emergency Physicians Liaison (no conflicts) ciency nologist, AAP Section on Pediatric Pulmonology Representative (no conflicts) Sinsi Hernández-Cancio, JD: Parent/Consumer fl  Emphasis on parent satisfaction/ Nizar F. Maraqa, MD, FAAP: Pediatric In- Representative (no con icts) patient-centered outcomes in all fectious Disease Physician, AAP Section on In- research (ie, not LOS as the only fectious Diseases Representative (no conflicts) STAFF Caryn Davidson, MA measure) H. Cody Meissner, MD, FAAP: Pediatric In- fectious Disease Physician, AAP Committee on Linda Walsh, MAB

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APPENDIX 1 SEARCH TERMS BY *Upper Respiratory Infection Symp- Bronchiolitis AND (bronchodilator OR TOPIC toms epinephrine OR albuterol OR salbuta- mol OR corticosteroid OR steroid) Introduction MedLine *Hypertonic Saline MedLine (exp Bronchiolitis/ OR exp Bronchioli- ((“bronchiolitis”[MeSH]) OR (“respira- tis, Viral/) AND exp *Respiratory Tract MedLine tory syncytial viruses”[MeSH]) NOT Infections/ ((“bronchiolitis”[MeSH]) OR (“respira- “bronchiolitis obliterans”[All Fields]) Limit to English Language tory syncytial viruses”[MeSH]) NOT 1. and exp Natural History/ Limit to “all infant (birth to 23 “bronchiolitis obliterans”[All Fields]) 2. and exp Epidemiology/ months)” OR “newborn infant (birth AND (exp Saline Solution, Hypertonic/ to 1 month)” OR “infant (1 to 23 OR (aerosolized saline.mp. OR (exp 3. and (exp economics/ or exp months)”) AEROSOLS/ AND exp Sodium Chloride/)) “costs and cost analysis”/or OR (exp Sodium Chloride/ AND exp exp “cost allocation”/ or exp CINAHL “Nebulizers and Vaporizers”/) OR neb- cost-benefit analysis/ or exp “ ” “ ulized saline.mp.) “cost control”/ or exp “cost of (MM Bronchiolitis+ ) AND (MM Re- ” illness”/ or exp “cost sharing”/ spiratory Tract Infections+ ) Limit to English Language or exp health care costs/ or Limit to “all infant (birth to 23 exp health expenditures/) The Cochrane Library months)” OR “newborn infant (birth to 4. and exp Risk Factors/ Bronchiolitis AND Respiratory Infection 1 month)” OR “infant (1 to 23 months)”) Limit to English Language AND Humans Inhalation Therapies CINAHL AND (“all infant (birth to 23 months)” “ ” “ or “newborn infant (birth to 1 month)” *Bronchodilators & Corticosteroids (MM Bronchiolitis+ ) AND (MM Sa- ” or “infant (1 to 23 months)”) line Solution, Hypertonic ) MedLine CINAHL ((“bronchiolitis”[MeSH]) OR (“respira- The Cochrane Library (MM “Bronchiolitis+”) AND (“natural tory syncytial viruses”[MeSH]) NOT Bronchiolitis AND Hypertonic Saline history” OR (MM “Epidemiology”)OR “bronchiolitis obliterans”[All Fields]) (MM “Costs and Cost Analysis”)OR AND (exp Receptors, Adrenergic, β-2/ Oxygen (MM “Risk Factors”)) OR exp Receptors, Adrenergic, β/OR MedLine β β exp Receptors, Adrenergic, -1/ OR ((“bronchiolitis”[MeSH]) OR (“respira- The Cochrane Library adrenergic*.mp. OR exp ALBUTEROL/ tory syncytial viruses”[MeSH]) NOT Bronchiolitis AND (epidemiology OR OR levalbuterol.mp. OR exp EPINEPH- “bronchiolitis obliterans”[All Fields]) risk factor OR cost) RINE/ OR exp Cholinergic Antagonists/ OR exp IPRATROPIUM/ OR exp Anti-In- 1. AND (exp Oxygen Inhalation Therapy/ OR supplemental oxygen.mp. OR ox- Diagnosis/Severity flammatory Agents/ OR ics.mp. OR in- haled corticosteroid*.mp. OR exp ygen saturation.mp. OR *Oxygen/ad, MedLine Adrenal Cortex Hormones/ OR exp Leu- st [Administration & Dosage, Stand- exp BRONCHIOLITIS/di [Diagnosis] OR kotriene Antagonists/ OR montelukast. ards] OR oxygen treatment.mp.) exp Bronchiolitis, Viral/di [Diagnosis] mp. OR exp Bronchodilator Agents/) 2. AND (exp OXIMETRY/ OR oxi- “ limit to English Language AND (“all Limit to English Language AND (“all meters.mp.) AND (exp Reproduc- ” infant (birth to 23 months)” or “new- infant (birth to 23 months)” or “new- ibility of Results / OR reliability. born infant (birth to 1 month)” or born infant (birth to 1 month)” or mp. OR function.mp. OR technical fi “infant (1 to 23 months)”) “infant (1 to 23 months)”) speci cations.mp.) OR (percuta- neous measurement*.mp. OR CINAHL CINAHL exp Blood Gas Analysis/) (MH “Bronchiolitis/DI”) (MM “ Bronchiolitis+”) AND (MM Limit to English Language “Bronchodilator Agents”) Limit to “all infant (birth to 23 The Cochrane Library months)” OR “newborn infant (birth to Bronchiolitis AND Diagnosis The Cochrane Library 1 month)” OR “infant (1 to 23 months)”)

PEDIATRICS Volume 134, Number 5, November 2014 e1501 Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 CINAHL NOT “bronchiolitis obliterans”[All “Urinary Tract Infections+”) OR (MM (MM “Bronchiolitis+”) AND Fields]) “Bacteremia”)) ((MM “Oxygen Therapy”) OR (MM “Ox- AND (exp Fluid Therapy/ AND (exp The Cochrane Library ygen+”) OR (MM “Oxygen Saturation”) infusions, intravenous OR exp admin- OR (MM “Oximetry+”) OR (MM “Pulse istration, oral)) Bronchiolitis AND (serious bacterial Oximetry”) OR (MM “Blood Gas Moni- Limit to English Language infection OR sepsis OR otitis media OR meningitis OR urinary tract infection or toring, Transcutaneous”)) Limit to (“all infant (birth to 23 bacteremia OR pneumonia OR anti- months)” or “newborn infant (birth to bacterial OR antimicrobial OR antibi- The Cochrane Library 1month)” or “infant (1 to 23 months)”) otic) Bronchiolitis AND (oxygen OR oximetry) CINAHL Hand Hygiene, Tobacco, Chest Physiotherapy and (MM “Bronchiolitis+”) AND Breastfeeding, Parent Education Suctioning ((MM “Fluid Therapy+”) OR (MM “Hy- MedLine MedLine dration Control (Saba CCC)”) OR (MM ((“bronchiolitis”[MeSH]) OR (“respira- ((“bronchiolitis”[MeSH]) OR (“respira- “Hydration (Iowa NOC)”)) tory syncytial viruses”[MeSH]) NOT tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields]) “bronchiolitis obliterans”[All Fields]) The Cochrane Library fl 1. AND (exp Hand Disinfection/ OR 1. AND (Chest physiotherapy.mp. OR Bronchiolitis AND (hydrat* OR uid*) hand decontamination.mp. OR (exp Physical Therapy Techniques/ handwashing.mp.) AND exp Thorax/)) SBI and Antibacterials 2. AND exp Tobacco/ 2. AND (Nasal Suction.mp. OR (exp MedLine Suction/)) 3. AND (exp Breast Feeding/ OR ((“bronchiolitis”[MeSH]) OR (“respira- exp Milk, Human/ OR exp Bottle Limit to English Language tory syncytial viruses”[MeSH]) NOT Feeding/) Limit to “all infant (birth to 23 “ ” bronchiolitis obliterans [All Fields]) Limit to English Language months)” OR “newborn infant (birth to AND “ 1month)” OR “infant (1 to 23 months)”) Limit to ( all infant (birth to 23 (exp Bacterial Infections/ OR exp Bac- months)” or “newborn infant (birth to CINAHL terial Pneumonia/ OR exp Otitis Media/ 1 month)” or “infant (1 to 23 months)”) OR exp Meningitis/ OR exp *Anti-bac- (MM “Bronchiolitis+”) terial Agents/ OR exp Sepsis/ OR exp CINAHL 1. AND ((MH “Chest Physiotherapy Urinary Tract Infections/ OR exp Bac- (MM “Bronchiolitis+”) (Saba CCC)”)OR(MH“Chest Phys- teremia/ OR exp Tracheitis OR serious 1. AND (MH “Handwashing+”) ical Therapy+”)OR(MH“Chest bacterial infection.mp.) ” 2. AND (MH “Tobacco+”) Physiotherapy (Iowa NIC) )) Limit to English Language “ 3. AND (MH “Breast Feeding+” OR 2. AND (MH Suctioning, Nasopharyn- Limit to (“all infant (birth to 23 ” MH “Milk, Human+” OR MH “Bottle geal ) months)” or “newborn infant (birth to Feeding+”) 1month)” or “infant (1 to 23 months)”) The Cochrane Library The Cochrane Library Bronchiolitis AND (chest physiotherapy CINAHL Bronchiolitis OR suction*) (MM “Bronchiolitis+”) AND 1. AND (Breast Feeding OR breast- ((MM “Pneumonia, Bacterial+”)OR Hydration feeding) (MM “Bacterial Infections+”) OR (MM MedLine “Otitis Media+”) OR (MM “Meningitis, 2. AND tobacco ((“bronchiolitis”[MeSH]) OR (“respi- Bacterial+”) OR (MM “Antiinfective 3. AND (hand hygiene OR handwash- ratory syncytial viruses”[MeSH]) Agents+”) OR (MM “Sepsis+”) OR (MM ing OR hand decontamination)

e1502 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis Shawn L. Ralston, Allan S. Lieberthal, H. Cody Meissner, Brian K. Alverson, Jill E. Baley, Anne M. Gadomski, David W. Johnson, Michael J. Light, Nizar F. Maraqa, Eneida A. Mendonca, Kieran J. Phelan, Joseph J. Zorc, Danette Stanko-Lopp, Mark A. Brown, Ian Nathanson, Elizabeth Rosenblum, Stephen Sayles III and Sinsi Hernandez-Cancio Pediatrics originally published online October 27, 2014;

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since . Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2014 by the American Academy of Pediatrics. All rights reserved. Print ISSN: .

Downloaded from http://pediatrics.aappublications.org/ by guest on April 27, 2018 2. On page e1358, in the section on Spinosad (0.9% Suspension), the second sentence should have read: “It is not recommended for children younger than 6 months because it also contains benzyl alcohol.” (instead of “It is contraindicated…”).

3. On page e1358, in the section on Spinosad (0.9% Suspension), the last sentence, which read, “Safety in children younger than 4 years has not been established.” should have been deleted. doi:10.1542/peds.2015-2696

Campbell et al. Critical Elements in the Medical Evaluation of Suspected Child Physical Abuse. Pediatrics. 2015;136(1):35–43 An error occurred in the article by Campbell et al, titled “Critical Elements in the Medical Evaluation of Suspected Child Physical Abuse” published in the July 2015 issue of Pediatrics (2015;136[1]:35–43; doi:10.1542/peds.2014-4192). On page 41, in Table 2, under “Radiology” and “Skull Fracture,” this reads: “Head CT,a skeletal surveya.” This text should have read: “Head CT,b skeletal surveyb” (footnotes were incorrectly assigned). doi:10.1542/peds.2015-2823

Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis. Pediatrics. 2014;134 (5):e1474–e1502 An error occurred in the American Academy of Pediatrics article, titled “Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis published in the November 2014 issue of Pediatrics (2014;134[5]:e1474–e1502). On page e1484, in the discussion after Key Action Statement 6b, in the fifth paragraph, the sentence reading “In 1 study of 64 healthy infants between 2 weeks and 6 months of age, 60% of these infants exhibited a transient oxygen desaturation below 90%, to values as low as 83%.” should have been attributed to reference 104 (Hunt CE et al) instead of 105. doi:10.1542/peds.2015-2862

Kurowski et al. Online Problem-Solving Therapy for Executive Dysfuntion After Child Traumatic Brain Injury. Pediatrics. 2013;132(1):e158–e166 An error occurred in the article by Kurowski et al, titled “Online Problem-Solving Therapy for Executive Dysfunction After Child Traumatic Brain Injury” published in the July 2013 issue of Pediatrics (2013;132[1]:e158–e166; doi: 10.1542/peds.2012-4040). On page e163, under the Results section, in Tables 3 and 4, the baseline and 6 month

TABLE 3 Improvements From Baseline to Follow-up on the Global Executive Composite (GEC) in the CAPS Versus IRC Treatments in the Entire Sample Older Teens (9th–12th Grade) and Younger Teens (6th–8th Grade) CAPS (n 5 57) IRC (n 5 62a) F (df ) Pb

Mean (SD) Mean (SD)

Baseline 6 Month Change Baseline 6 Month Change Entire Samplea 58.53 (10.11) 57.00 (11.40) 21.53 (8.75) 61.56 (10.74) 60.16 (12.16) 21.40 (7.43) 0.17 (118) 0.68 Older Teensa 60.15 (10.51) 55.37 (11.44) 24.78 (6.66) 61.54 (10.98) 60.69 (10.94) 20.86 (5.98) 6.74 (61) 0.01 Younger Teens 57.07 (9.69) 58.47 (11.37) 1.40 (9.46) 61.59 (10.63) 59.48 (13.77) 22.11 (9.06) 1.27 (56) 0.27 CAPS 5 Counselor Assisted Problem Solving, IRC 5 Internet Resource Comparison a The total study participants for IRC was 63; however, one participant did not completed the Behavioral Rating Inventory (BRIEF)-Behavioral Regulation Index (BRI) Inhibit subscale, so the GEC could not calculated for this participant and they were excluded from this analysis. b P values apply to differences between CAPS and IRC groups as measured by general linear models after controlling for baseline scores.

782 ERRATA Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis Shawn L. Ralston, Allan S. Lieberthal, H. Cody Meissner, Brian K. Alverson, Jill E. Baley, Anne M. Gadomski, David W. Johnson, Michael J. Light, Nizar F. Maraqa, Eneida A. Mendonca, Kieran J. Phelan, Joseph J. Zorc, Danette Stanko-Lopp, Mark A. Brown, Ian Nathanson, Elizabeth Rosenblum, Stephen Sayles III and Sinsi Hernandez-Cancio Pediatrics originally published online October 27, 2014;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/early/2014/10/21/peds.2014-2742

An erratum has been published regarding this article. Please see the attached page for: http://pediatrics.aappublications.org//content/136/4/782.2.full.pdf

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since . Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2014 by the American Academy of Pediatrics. All rights reserved. Print ISSN: .

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