Clinical Practice Guideline Viral Bronchiolitis

OUTLINE I. Intention/Purpose Statement II. Clinical Inpatient Protocol (CLIP) III. Patient Information Sheet IV. Introduction A. Epidemiology B. Pathogenesis C. Outcomes V. Diagnosis A. Diagnostic Criteria B. Viral Testing C. Chest Radiography D. Complete Blood Counts E. Assessment for Risk of Severity/Complications VI. Management A. Hospitalization Criteria B. Prevention of Nosocomial Transmission C. Supportive Care D. Supplemental Oxygen E. Inhaled Beta-Agonists F. Inhaled Epinephrine G. Corticosteroids H. Antibiotics I. Ribavirin J. Inhaled Hypertonic Saline VII. Complications A. Predictors of Disease Severity at Presentation B. Need for Ventilatory Support C. Concurrent Bacterial Pneumonia D. Hyponatremia E. Other Extrapulmonary Complications VIII. Discharge Criteria IX. Discharge Anticipatory Guidance. X. References I. INTENTION/PURPOSE STATEMENT UNC Pediatric Inpatient Clinical Practice Guidelines (CPGs) are evidence-based decision-making tools designed to optimize the inpatient management of common pediatric illnesses. In addition to guiding clinicians in the delivery of high quality medical care tailored to the individual patients needs, these guidelines will improve resource utilization, patient safety, clinical efficiency, and patient throughput. These recommendations are not intended to replace clinical judgment and may not universally apply to all patients. These guidelines are consistent with the American Academy of Pediatrics 2006 guidelines on the diagnosis and management of bronchiolitis. General recommendations are italicized.

II. CLINICAL INPATIENT PROTOCOL (CLIP): BRONCHIOLITIS

Adapted from American Academy of Pediatrics, Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and Management of Bronchiolitis. Pediatrics. 2006; 118(4):1774-93.

Patient diagnosed with bronchiolitis Patient at risk for severe disease or needing ICU level care?

yes no
SpO2 consistently < 90% on room air?

Individualized therapy

yes no
Bulb suction nose/mouth, reposition airway, re-position pulse oximetry probe Consider Bronchodilator Trial*, particularly if history of wheezing or + FHx allergic disease

SpO2 consistently < 90% on room air? +/- Unable to maintain oral hydration? +/- RR> 70 bpm? +/- Severely increased WOB? +/- Significant caregiver anxiety?

no
Discharge when criteria met

yes
Admit to general pediatrics

Implement preventive measures to decrease nosocomial transmission Provide supportive care and monitoring Titrate supplemental oxygen to maintain SpO2 consistently 90%

Bronchodilator trial desired or positive trial in ED?

yes

See Bronchodilator Trial Instruction

no
Aggressively wean oxygen to maintain SpO2 between 90-94% (weaning per RT)

Patient improving as anticipated?

no

Consider CXR; re-evaluate dia

yes
Discontinue continuous pulse oximetry when patient clinically improving

Discharge when criteria met

*Bronchodilator Trial Instructions5

Bulb suction nasopharynx, re-position airway; allow child to recover to baseline

Assign pre-trial RDAI clinical score Administer one dose of inhaled albuterol Assign post-trial RDAI clinical score within 15 minutes after treatment completed RDAI score decreased by 3 points? yes no

Continue albuterol and consider systemic steroids

Discontinue albuterol

RT to continue assigning Table 1. Respiratory Distress Assessment Instrument89

III. PATIENT

RDAI score pre/post treatment and wean inhaled INFORMATION SHEET: Viral Bronchiolitis* medication as appropriate

What is bronchiolitis? Bronchiolitis is a lower lung infection caused by a virus, most commonly RSV (Respiratory Syncytial Virus). It occurs only in children less than 2 years old. The symptoms of bronchiolitis include: Wheezing (making a high-pitched whistling sound when breathing out) Taking more than 40 breaths per minute Using extra muscles to breathe (working harder to breathe than normal) Coughing Fever Runny nose and "cold" symptoms before the breathing problems started Your child's healthcare provider will make the diagnosis based on your child's symptoms and physical examination. Special testing and x-rays are not necessary. How did my child get it? Viruses that cause bronchiolitis are spread through the air by coughing, sneezing, or direct contact (hand-to-hand, hand-to-eyes/nose/mouth). The viruses are very contagious during the first few days of illness. How long will the symptoms last? The breathing problems usually become worse for 2 to 3 days, and then begin to improve. The cough may last as long as 3 weeks. What medications can be used for it?

There are no medications that completely clear up the symptoms of bronchiolitis. Antibiotics are usually not required, and are not effective for illnesses caused by viruses. Over-the-counter decongestants and cough suppressants are not recommended for children less than 2 years old due to safety concerns. Acetaminophen (Tylenol) can be used for fever, fussiness, or discomfort. In infants over six months of age, ibuprofen (Children's Motrin) may be used instead of acetaminophen. Aspirin should never be used in children due to the high risk of liver and neurologic damage. If your child's symptoms improve with inhaled albuterol treatments, your healthcare provider may prescribe this medication. Your child may be more susceptible to wheezing with future viral illnesses and/or asthma, which you should discuss with your child's regular healthcare provider. How else can I take care of my child? Hydration: Encourage your child to drink plenty of fluids, preferably breast milk, formula, Pedialyte, or whole milk (if over 12 months of age) in small amounts more frequently. If your child vomits during a coughing spasm, feed him/her again. Feeding: It's okay if your child does not want to eat solid foods for a few days as long as he/she will drink enough fluids. Suctioning the nose: Suction alone will not remove dry secretions. Warm tap water or saline nosedrops are best to help clear the nose if congestion is interfering with feeding or sleeping. You can make saline nosedrops by adding teaspoon of table salt to 1 cup of water. Place three drops of warm water or saline in each nostril. After one minute, use a soft rubber suction bulb to suck out the mucus. You can repeat this procedure several times until your child's breathing through the nose becomes quiet and easy. Coughing: Warm liquids help to relax the airway and loosen the mucus. Use a humidifier in the room where your child sleeps. Avoid steam vapors and overheated cloths as these can cause burns. Propping the head of the bed up with pillows or a 6 inch block may also help. Tobacco smoke exposure, including smoke in the clothing and on the skin of smokers, makes coughing worse and should be avoided. Activity: Your child may return to daycare when the fever is gone and he/she is eating well and feeling better. Encourage frequent naps to help recovery. Hand washing: Because viruses that cause bronchiolitis are very contagious, wash your hands for at least 20 seconds with soap and warm water before and after touching your child or any object that has had contact with your child. Alcohol-based hand sanitizers also effectively kill the viruses. When should my child be seen again? _____We have scheduled an appointment for your child with ____________________ on ____________________ at __________am / pm. _____Your child needs to be rechecked in ___ days. Call your child's healthcare

provider to schedule an appointment. _____You may schedule an appointment with your child's healthcare provider as needed. What symptoms should I be watching for that would require me to call my child's health care provider or come to the emergency room? Child is not starting to improve after 24-48 hours Very rapid breathing: o Birth to 6 weeks oldover 60 breaths per minute o 6 weeks to 2 years oldover 45 breaths per minute Fever more than 104 orally or more than 102 for 3 consecutive days. Earache, stiff neck, headache, repeated vomiting or diarrhea Worsening or persistent fussiness, drowsiness, confusion No wet diapers for 8 hours, "sunken" eyes, no tears when crying, dry mouth
*The intended use of the information presented above is for education and is not a replacement for medical advice or evaluation by a healthcare professional.

IV. INTRODUCTION A. Epidemiology Bronchiolitis is an acute, potentially life-threatening viral infection of the lower respiratory tract. It is the leading cause of hospitalization of children in the US81 with yearly hospital charges totaling up to $700 million118. In the past 3 decades, the proportion of infant hospitalizations due to bronchiolitis has more than tripled. Despite the increase in hospitalization rates, mortality from bronchiolitis has dramatically fallen over the past 3 decades, from 4500 deaths in 1985119 to 390 in 199982. Respiratory syncytial virus (RSV) is responsible for causing nearly 70% of bronchiolitis, with the remainder of cases due to human metapneumovirus (HMPV), influenza, parainfluenza, adenovirus, rhinovirus, and, sporadically, mycoplasma144. Co-infection with more than one of these viruses has been reported and may be responsible for more severe disease1,116. Bronchiolitis occurs in predictable annual intervals worldwide, with an average onset in late December and peak in February in the US. During the 2006-2007 bronchiolitis season at UNC, 59 patients with bronchiolitis were admitted to the general pediatrics inpatient service. When data for these patients were examined retrospectively, adherence to the 2006 AAP guidelines for the diagnosis and management of bronchiolitis was generally poor74. Complete blood counts and chest radiography were obtained for 43% and 78%, respectively. Of patients who underwent chest radiography, 55% were RSV positive and only 3% had documentation of change in management based on xray findings. Transitioning from continuous to intermittent pulse-oximetry monitoring was documented for only 13% of patients. Albuterol was given at least once to 57% of patients, with 52% of these patients having no history of wheezing and 80% lacking documentation of response to treatment. B. Pathogenesis The viruses that cause bronchiolitis are spread by direct inoculation of infected secretions from contaminated fomites and by large particle aerosols entering through the eyes and nose62. Upon inoculation, RSV replicates in the nasopharynx and presumably spreads along the respiratory epithelium to the lower respiratory tract. Small airways become inflamed and edematous, resulting in destruction and necrosis of ciliated epithelial cells and increased mucus production6. Airways become physically obstructed with mucus and cellular debris. C. Outcomes Typically, symptoms peak on the third day of illness and resolve by 7-10 days. Most will have normal respiratory parameters 2 weeks after the height of the illness and radiologic abnormalities will clear within 9 days of admission106. The link between infant bronchiolitis and recurrent wheezing has not been clearly elucidated. A recent study found no difference in pulmonary function studies between 29 full term, age, race and sex matched control infants without prior wheezing, asthma or lower respiratory illness when compared to a similar

group of 29 previously healthy infants admitted with a first episode of acute RSV bronchiolitis39. Infants hospitalized with severe bronchiolitis have been observed to have more respiratory problems as older children, especially recurrent wheezing, when compared with those who did not have severe disease92,114,123. V. DIAGNOSIS A. Diagnostic Criteria *Recommendation: Bronchiolitis should be diagnosed based on history and physical examination Bronchiolitis is a clinical diagnosis which should be based on clinical history and physical exam. The wide range of clinical symptoms and severity can make diagnosis challenging, but consistent features include: Preceding upper respiratory symptoms, including rhinorrhea and fever Signs/symptoms of respiratory distress o Wheezing o Retractions o Nasal flaring o Tachypnea o Hypoxia/cyanosis o Crackles o Cough Difficulty feeding and/or dehydration secondary to respiratory distress B. Viral Testing *Recommendations 1. Rapid viral testing is not routinely recommended. 2. Rapid viral testing may be considered in febrile infants < 3 months of age to limit further laboratory testing and prevent the unnecessary use of broad-spectrum antibiotics. Viral culture remains the gold standard for establishing the etiology of bronchiolitis. Most clinical studies, however, have used rapid RSV antigen detection tests such as direct immunofluoresence (DFA) and enzyme immunoassay (EIA), which have an overall sensitivity of 80-90%. Viral culture, DFA, and EIA have all been shown to have better sensitivity and accuracy when performed on nasopharyngeal aspirates rather than nasopharyngeal swabs7. At UNC, EIA is the rapid antigen test performed. Although rapid viral testing is widely available for RSV, no data exists to suggest that knowing the cause of the disease alters clinical outcomes. However, rapid viral testing in febrile patients < 3 months of age may prevent additional workup20,135 and reduce unnecessary treatment with broad-spectrum antibiotics4,24. Testing also allows for cohorting of patients and staff to decrease nosocomial transmission, although this technique lacks efficacy data.

C. Chest radiography *Recommendations 1. Chest radiography is not routinely recommended in cases of uncomplicated bronchiolitis. 2. Chest radiography may be considered if the diagnosis is unclear or if the patient is not recovering as anticipated. Commonly cited reasons for obtaining chest radiography are to rule-out bacterial pneumonia and to assess disease severity. However, insufficient evidence exists to support the ability of chest radiography to distinguish between viral and bacterial disease20, particularly since chest x-ray appearance may be normal in patients with clinical signs of pneumonia68. Also, no correlation has been found between clinical respiratory distress scores, as a measure of disease severity, and chest x-ray appearance37. Chest x-ray findings in bronchiolitis are non-specific and variable, but may include a normal appearance, patchy atelectasis, peribronchial thickening, perihilar prominence, airspace disease, and/or hyperinflation37,115. Among children with clinical signs and symptoms consistent with mild to moderate bronchiolitis, chest radiography has been found to be consistent with the diagnosis in >99%115, suggesting that chest radiography adds no additional information beyond physical examination in cases of clear-cut bronchiolitis. There is also no evidence that obtaining chest x-rays improves outcome for children with lower respiratory tract disease126. Therefore, routine chest x-rays are not recommended in uncomplicated bronchiolitis. Of note, use of chest radiography has been associated with increased use of antibiotics, but no difference in time to resolution of symptoms was found127. D. Complete Blood Counts (CBCs) *Recommendation: CBCs are not routinely recommended. CBCs have been found to have low specificity and positive predictive value in the diagnosis of viral illness. The use of complete blood counts has not been shown to be useful in either diagnosing bronchiolitis or guiding its therapy5,103. E. Assessment for Risk of Severity/Complications *Recommendation: Patients should be assessed for factors and/or co-morbidities which may increase the risk for severe or complicated disease (see Section V. Complications below), including: Age < 12 weeks Presence of chronic lung disease Presence of hemodynamically-significant congenital heart disease Presence of immunodeficient state Presence of a genetic defect or chronic disease which could decrease the patient's ability to compensate for acute illness

History of prematurity (< 35 weeks gestational age) Respiratory rate > 70 bpm

The presence of any of the above factors and/or co-morbidities warrants exclusion from this guideline and management should be tailored to the individual needs of the patient. VI. MANAGEMENT A. Hospitalization Criteria Inability to maintain consistent oxygen saturations >90% on room air; and/or Inability to maintain adequate oral hydration; and/or Respiratory rate greater than 70 breaths per minute; and/or Severely increased work of breathing; and/or Caregiver anxiety requiring more extensive education; and/or Additional consideration for hospitalization should be given to children at risk for severe or complicated disease, as listed under Section V. Diagnosis, item E. B. Prevention of Nosocomial Transmission. *Recommendations 1. Use adequate hand sanitation before and after contact with the patient or inanimate objects in the vicinity of the patient using an alcohol-based rub or hand washing with antimicrobial soap. 2. Clinicians should educate personnel and family members on hand sanitation and other techniques for decreasing viral spread. 3. Implement contact and droplet precautions in addition to standard universal precautions. 4. Patients and staff should be cohorted as feasible. Because frequent hand-washing has been shown to decrease nosocomial viral spread113, hands should be decontaminated before and after contact with the patient and/or inanimate objects in the vicinity of the patient. All health care providers and visitors should be educated in preventing patient-to-patient viral transmission and hand sanitation techniques, including the use of alcohol foam and antimicrobial soap and water21. In addition to implementing universal standard precautions, contact and droplet precautions should be initiated given the ability of the causative viral agents to spread via contaminated fomites and large particle entry into eyes and nose83,89. Patients and staff should be cohorted, when feasible, as this has been shown to decrease nosocomial viral transmission41. C. Supportive Care and Monitoring *Recommendations 1. Patients should be assessed for the ability to maintain hydration orally. Oral hydration should be maintained as the patient can tolerate. 2. If the patient is unable to take sufficient volume to maintain oral

3. 4. 5. 6.

hydration or cannot feed safely, intravenous fluids should be administered. While receiving IV fluids, the patient should be carefully monitored for the development of hyponatremia. Nasal/oral bulb suctioning should be used to clear secretions prior to feeding (if necessary), prior to inhaled medication trials, and as needed for temporary relief of airway obstruction. Chest physiotherapy and deep nasopharyngeal suctioning are not routinely recommended. Infants < 4 weeks of age should be placed on cardiorespiratory monitors due to the increased risk of apnea. Cardiorespiratory monitoring may be considered for infants between 4 weeks and 12 weeks of age due to the increased risk of apnea.

Infants with respiratory distress and tachypnea have increased energy expenditure and insensible fluid losses. Patients may have difficulty maintaining adequate oral intake given this increased fluid requirement, particularly if respiratory distress interferes with feeding. Also, patients with respiratory rates greater than 60-70 bpm may be at increased risk of aspiration of feeds75. If the patient is unable to take in sufficient volume to maintain hydration or cannot feed safely, intravenous fluids should be provided. Given sporadic reports of hyponatremia due to fluid retention, however, serum sodium levels should be closely monitored during intravenous fluid administration57,138 (see Section V, item D below). In terms of airway clearance, only nasal bulb suctioning and maintenance of proper airway positioning have been found to be helpful in managing bronchiolitis. Three RCTs have failed to demonstrate any benefit of chest physiotherapy using vibration and percussion techniques18,96,144. No data exists evaluating the safety and efficacy of routine deep pharyngeal suctioning. D. Supplemental Oxygen *Recommendations 1. Supplemental oxygen should be administered if the patient is unable to maintain oxyhemoglobin saturation (Sp02) consistently at or above 90% after nasal and/or oral suctioning, appropriate airway positioning, and pulse oximetry probe repositioning. 2. Oxygen should be titrated primarily by respiratory therapy staff to maintain Sp02 at or above 90% during both feeding and sleep. 3. Continuous pulse oximetry measurement may be discontinued as the patient is clinically improving. Data are lacking to identify specific criteria at which patients with bronchiolitis should be given supplemental oxygen and/or hospitalized. The relationship between SpO2 and the arterial partial pressure of oxygen (PaO2) suggests that at or above SpO2 of 90%, otherwise healthy children with bronchiolitis are unlikely to receive significant benefit from the application of supplemental oxygen. Because transient decreases in SpO2 below 90% occur

even in healthy children70, supplemental oxygen should not be initiated until persistent decreases in SpO2 below 90% are observed. Patients should be observed during both sleep and feeding, as these states alter ventilatory effort and metabolic demand, respectively. Because poor probe positioning and motion artifact can interfere with the accuracy of pulse oximetry readings, the probe should be repositioned prior to initiating supplemental oxygen. Finally, the childs clinical work of breathing should also factor into the decision to start supplemental oxygen. Once oxygen therapy is initiated, flow rates should be titrated primarily by respiratory therapy staff to maintain SpO2 at or above 90% during both feeding and sleep. As the patients clinical status begins to improve, continuous pulse oximetry should be replaced with intermittent pulse oximetry measurement. E. Inhaled Beta-Agonists *Recommendations 1. Inhaled bronchodilators are not routinely recommended. 2. A carefully monitored trial of an inhaled bronchodilator is an option. Nasal suctioning and appropriate airway positioning should be performed prior to the initiation of the trial. The patient should be allowed to return to baseline. The Respiratory Distress Assessment Instrument (RDAI; See CLIP Table 1) should be used by an MD or respiratory therapist to assign a clinical score immediately before and within 15 minutes after treatment completion. Inhaled bronchodilators should be continued only if positive treatment response has been documented using the RDAI. Given the significant benefits of inhaled beta-adrenergic agonists in the treatment of asthma, clinicians have chosen to use these agents in bronchiolitis despite the paucity of evidence to support the practice. Multiple randomized, controlled trials (RCTs) have been published to date in which the effects of inhaled albuterol or salbutamol were compared to placebo in children hospitalized with acute bronchiolitis26,28,29,40,56,61,69,72,87,90,100,131,137,142. When data were pooled, no significant benefit of beta-adrenergic agonist treatment was noted among inpatients, particularly with respect to shortened symptom duration or length of stay53. These results are consistent with the underlying pathogenesis of bronchiolitis being obstruction of small airways with cellular debris and mucus, as opposed to functional obstruction via bronchospasm. Thus, the routine use of beta-adrenergic agonist treatment is not recommended. Given the possibility of underlying reactive airways disease in children presenting with bronchiolitis, a trial of beta-adrenergic agonist treatment, in which the patients response is carefully monitored, is an option8. At UNC, the trial should be conducted by an MD or a respiratory therapist using inhaled albuterol. Prior to administering the medication, the child's nasal and oral airways should be bulb suctioned and the child should be allowed to recover to baseline after suctioning. The Respiratory Distress Assessment Instrument (RDAI), a validated

tool used in many bronchiolitis studies to objectively characterize clinical work of breathing88, should be used to assign a clinical score immediately before and again within 15 minutes after completion of administration of the medication. The trail is considered positive, meaning the child shows improvement due to the medication, if the post-treatment RDAI score is 3 or more points lower than the pre-treatment score. Inhaled beta-agonists should only be continued if a positive trial is documented. The child should subsequently be considered to have underlying reactive airways disease and managed accordingly. F. Inhaled Epinephrine *Recommendations 1. Inhaled epinephrine is not routinely recommended. 2. A carefully monitored trial of inhaled epinephrine is an option. (See Section VI. Management, Item E, Recommendation 2, above) Multiple RCTs have been published to date in which the effects of inhaled epinephrine were compared with either an inhaled beta-adrenergic agonist or placebo in children hospitalized with acute bronchiolitis3,17,77,81,100,104,112,140,143. Shortterm improvements in clinical respiratory scores and/or pulse-oximetry measurements were observed in four studies77,104,112,143. Length of stay was not effected in four studies which reported this outcome17,81,100,104. Pooled data demonstrate insufficient evidence to suggest that the routine use of inhaled epinephrine alters the course of illness67. Given the possibility of underlying reactive airways disease and the demonstrated short-term benefits, a trial of inhaled epinephrine, in which the patients response to treatment is carefully observed, is an option8. The RDAI should be used to assign a clinical score immediately before one dose of inhaled epinephrine and again within 15 minutes after treatment completion. Inhaled epinephrine should be continued only if a positive response is documented using the RDAI. On the general pediatric inpatient service at UNC, inhaled epinephrine should be given no more than every 2 hours. Patients should be on cardiorespiratory monitors during and at least 3 hours after treatment. G. Corticosteroids *Recommendations 1. Corticosteroids, in any form, are not routinely recommended. 2. Corticosteroids may be considered if a positive treatment response to inhaled bronchodilators has been documented, with the presumption of the existence of underlying reactive airways disease. Various RCTs have examined the efficacy of various oral, inhaled, and parenteral corticosteroids on symptoms and clinical course of children hospitalized with bronchiolitis with mixed results15,16,23,25,27,32-36,38,55,76,79,84,107,111, 122,131,133,137,139,146,148 . Trial design, choice and dosage of drug, and reported outcome

variables are extremely heterogeneous, making comparison between studies difficult. Not surprisingly, pooled data do not show a statistically significant difference in lengths of stay or clinical symptoms99. Despite the existence of RCTs with sample sizes greater than 100, the efficacy of corticosteroids remains unclear. Three large RCTs were devoted to examining oral steroid usage23,33,34. The only study with positive results, specifically shorter length of stay and duration of symptoms in the treatment group, included infants with prior history of wheezing34. Interestingly, two placebo-controlled studies with similar designs examined the use of intramuscular dexamethasone in infants with bronchiolitis and no history of wheezing: one found no difference between groups111 and the other found significantly shorter symptom duration and length of stay in the dexamethasone group133. Two large conflicting RCTs studying inhaled steroids have been conducted: one showing no difference25 and one showing significantly decreased length of stay and better clinical respiratory score in the steroid-treated group36. The later study, however, did not exclude infants with a history of wheezing. These unclear benefits must be weighed against the extensive list of potential adverse effects of steroids, including gastrointestinal bleeding11, complicated severe varicella42, cerebral palsy and neurodevelopmental impairment13, adrenal suppression, decreased linear velocity, and change in bone mineral density73,98. Therefore, insufficient data exists to support the use of any form of corticosteroid for the treatment of bronchiolitis. H. Antibiotics *Recommendations 1. Antibiotics are not routinely recommended. 2. Antibiotics should be used for specific indications of coexisting bacterial infection, following established guidelines for treatment in the absence of bronchiolitis. There have been very few randomized trials examining the efficacy of antibiotics in bronchiolitis. Two studies found no difference in length of stay or symptom duration in infants randomized to ampicillin or placebo groups50,52. A more recent small study with 21 patients found that treatment with clarithromycin decreased length of stay, duration of oxygen requirement, and need for beta(2)agonist treatment129. Concern for serious bacterial infection (SBI) in infants with bronchiolitis who are less than 90 days old has led to the use of broad-spectrum antibiotics. No studies examining the incidence of SBI specifically in infants <90 days old hospitalized with bronchiolitis have been reported. One prospective emergencyroom based study including only infants <90 days old found overall rate of SBI in RSV-positive children to be 7%, versus 12% in RSV-negative children85. Rates of urinary tract infection (UTI) and bacteremia in RSV-positive children were 5.4% and 1.1%, respectively.

In various retrospective and prospective studies, the rate of SBI in hospitalized patients with bronchiolitis was found to be extremely low, with urinary tract infection being the most common. In retrospective studies including children < 36 months, the rate of culture-proven SBI for children hospitalized with bronchiolitis was <1.9% of over 3000 patients collectively12,102,105. Prospectively, SBI rates of 1.2 % of 565 inpatients65, and 1.9% of 156 outpatients78 were cited. Of studies reporting UTI incidence, the rates of UTI in patients with bronchiolitis were < 1.9%78,102,135. Of studies reporting bacteremia incidence, the rates of true positive blood cultures were <1.1%58,78,86,102,135. Of note, one study found that infants exposed to antibiotics had a higher rate of subsequent bacterial infection65. Frequently cited reasons for the use of antibiotics in children with bronchiolitis are the co-existence of acute otitis media (AOM) and bacterial pneumonia. In one study, 84% of children with bronchiolitis were diagnosed with AOM at some point in their course, with 100% of those with AOM on physical exam having positive bacterial cultures from middle ear aspirates10. However, the majority of cases of uncomplicated AOM resolve spontaneously, obviating the need for antibiotics54,91,130. In reference to pneumonia, clinical outcome was not affected by significantly higher antibiotic use in one of two groups of children meeting the WHO case definition for pneumonia127. Thus, the decision to use antibiotics in these two situations must be weighed carefully against possible side effects. I. Ribavirin *Recommendations 1. Ribavirin is not routinely recommended. 2. Ribavirin may be considered in RSV-positive children with severe disease, or those at risk for severe disease. Ribavirin (1-beta-D-ribafuranosyl-1,2,4-triazole-3-carbox-amide) is a synthetic nucleoside analog that resembles guanosine and inosine123. It appears to interfere with the expression of messenger RNA and inhibit viral protein synthesis. Various RCTs evaluating ribavirin in the acute phase of illness found conflicting results14,49,59,60,63,64,71,93,110,120,128. Each study had a small sample size of 26 to 53 patients and trial designs and outcomes were varied and inconsistent. When the high drug cost51 is weighed against the likely marginal benefits, insufficient evidence exists to routinely recommend ribavirin in the treatment of bronchiolitis. However, ribavirin may be considered in RSV-positive children with severe disease, or those at risk for severe disease8. J. Inhaled Hypertonic Saline *Recommendation: Insufficient data exists at this time to routinely recommend the use of inhaled hypertonic saline. Inhaled hypertonic saline has been well-studied in the cystic fibrosis population, and found to be safe and effective in improving clearance of small

airways47,48,108,124. Although the exact mechanism is unknown, it is thought that hypertonic saline facilitates inspissated mucus removal and decreases mucosal edema109,136. In two RCTs evaluating 3% nebulized saline in children hospitalized with bronchiolitis, statistically significant improvements in clinical scores and reductions in length of stay were seen80,132. Despite these promising preliminary results, the safety of nebulized hypertonic saline remains in question due to observed bronchospasm after treatment in older patients with cystic fibrosis125. Although no significant adverse effects were noted in the two studies using inhaled 3% saline the treatment of bronchiolitis80,132, both studies allowed and/or required the co-administration of bronchodilators. Therefore, insufficient data exists at this time to recommend the routine use of hypertonic saline. VII. COMPLICATIONS A. Predictors of Disease Severity At Presentation Ill or toxic appearance117 Oxygen saturation <95%117 Gestational age <34 weeks117 Respiratory rate >70 breaths per minute117 Age <3 months117 Cyanosis94 Crackles94 Congenital heart disease147 Chronic lung disease147 B. Need for Ventilatory Support The primary complications requiring ventilatory support are respiratory insufficiency due to fatigue and apnea. Up to 20% of hospitalized infants develop apnea, which may be the presenting symptom9,30. Apnea is more likely in young infants and has been associated with an increased risk for prolonged hospitalization and admission to intensive care22,141. Apnea is typically non-obstructive central apnea during sleep early in the course of disease and rarely lasts more than a few days. However, about 10% of patients may require mechanical ventilation until apnea ceases2. C. Concurrent Bacterial Pneumonia Among infants with severe disease requiring admission to an intensive care unit, higher rates of bacterial pneumonia have been documented43,134. Infants with a history of prematurity have also been observed to have nearly triple the rate of co-existing bacterial infection as term infants105. D. Hyponatremia Pulmonary diseases, including viral bronchiolitis, are well-known to cause the syndrome of inappropriate ADH secretion (SIADH) via non-osmotic triggers. In a recent study including infants with severe bronchiolitis, 33% of RSV positive

patients experienced hyponatremia associated with increased ADH secretion44. The risk of hyponatremia appears to have an even greater correlation with the administration of hypotonic intravenous fluids66. Thus, patients should be monitored carefully for hyponatremia while receiving IV fluids and oral hydration should be reinitiated as quickly as possible. E. Other Extrapulmonary Manifestations During RSV infection, viremia and disseminated infection has been described44. Cardiac complications include arrhythmias, such as atrial and ventricular tachycardia, hypotension with shock97, and myocarditis19,101. Along with central apnea, neurologic complications include seizures in up to 1.8% of inpatients95. Hepatic involvement has also been described, ranging from mild transaminitis to severe hepatitis with coagulopathy45,46. VIII. DISCHARGE CRITERIA Discharge from the hospital is appropriate when the following criteria are met: Patient is able to maintain consistent oxygen saturation >90% on room air, or the patient is able to maintain consistent oxygen saturation >90% on a stable and minimal amount of supplemental oxygen Patient is free of apnea for >24 hours Patient is able to maintain adequate hydration with oral or enteral tube feeding Caregivers have been adequately educated and feel comfortable providing necessary care for the patient (see Section IX. Discharge Anticipatory Guidance, below) More than 3 hours have elapsed since the last inhaled epinephrine treatment Caregiver has ability to access medical care as needed Appropriate hospital follow-up and/or home health care, if necessary, has been arranged, including detailed communication with the primary care provider about issues requiring follow-up IX. DISCHARGE ANTICIPATORY GUIDANCE Prior to discharge, caregivers should be educated at an appropriate level of understanding about each of the following: Airway positioning Airway clearance techniques, including nasal suction Maintenance of oral hydration Temperature control, including appropriate dosages of antipyretics Use of any prescribed medications Avoidance of exposure to tobacco smoke or other irritants Methods to limit transmission (eg, hand washing, avoiding day care while ill) Criteria for immediate return to a health care provider Timing of scheduled follow-up with primary healthcare provider

Compiled Jan 2008 by the University of North Carolina General Pediatric Clinical Practice Guidelines Development Committee Authors: Mikelle Key-Solle, MD, General Pediatrics; primary author Kathy Bradford, MD, General Pediatrics Julie Byerley, MD, General Pediatrics Harvey Hamrick, MD, General Pediatrics Cheryl Jackson, MD, Pediatric Emergency Medicine Jacob Lohr, MD, General Pediatrics Kyrie Shomaker, MD, General Pediatrics Michael Steiner, MD, General Pediatrics Consultants: Ki Abel, MD, Pediatric Emergency Medicine Kara Bozik, PharmD Michael Goley, PNP Jessica Katz-Nelson, MD, Pediatric Emergency Medicine Tiffany Mabe, RRT, Pediatric Respiratory Therapy Dan Macklin, Pediatric Emergency Medicine

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