{'fraction_non_alphanumeric': 0.030529481454479177, 'fraction_numerical': 0.013259819557094687, 'mean_word_length': 5.588712098468928, 'pattern_counts': {'":': 0, '<': 14, '<?xml version=': 0, '>': 2, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Pediatric respiratory distress: California out‐of‐hospital protocols and evidence‐based recommendations

Abstract Objectives Prehospital protocols vary across local emergency medical service (EMS) agencies in California. We sought to develop evidence‐based recommendations for the out‐of‐hospital evaluation and treatment of pediatric respiratory distress, and we evaluated the protocols for pediatric respiratory distress used by the 33 California local EMS agencies. Methods Evidence‐based recommendations were developed through an extensive literature review of the current evidence regarding out‐of‐hospital treatment of pediatric patients with respiratory distress. The authors compared the pediatric respiratory distress protocols of each of the 33 California local EMS agencies with the evidence‐based recommendations. Our focus was on the treatment of 3 main pediatric respiratory complaints by presentation: stridor (croup), wheezing < 24 months (bronchiolitis), and wheezing > 24 months (asthma). Results Protocols across the 33 California local EMS agencies varied widely. Stridor (croup) had the highest protocol variability of the 3 presentations we evaluated, with no treatment having uniform use among all agencies. Only 3 (9.1%) of the local EMS agencies differentiated wheezing in children < 24 months of age, referencing this as possible bronchiolitis. All local EMS agencies included albuterol and epinephrine (intravenous/intramuscular) in their pediatric wheezing (asthma) treatment protocols. The least common treatments for wheezing (asthma) included nebulized epinephrine (3/33) and magnesium (2/33). No agencies included steroids in their treatment protocols (0/33). Conclusion Protocols for pediatric respiratory distress vary widely across the state of California, especially among those for stridor (croup) and wheezing in < 24 months (bronchiolitis). The evidence‐based recommendations that we present for the prehospital treatment of these conditions may be useful for EMS medical directors tasked with creating and revising these protocols.


INTRODUCTION
Respiratory distress is the one of the most frequently encountered pediatric out-of-hospital medical complaints and is the top complaint in children < 1 year of age. [1][2][3] Prompt identification and treatment of the appropriate underlying cause of pediatric respiratory distress is a challenge for most emergency medical service (EMS) professionals. This is likely because pediatric respiratory distress differs significantly from adult respiratory distress. 4 In 2014, the American Academy of Pediatrics (AAP) made significant changes to bronchiolitis guidelines and the National Association of State EMS Officials (NASEMSO) 2019 National Model EMS Clinical Guidelines include a bronchiolitis pediatric-specific guideline.
With bronchiolitis being the leading cause of hospitalization in children < 2 years old and asthma the most common chronic childhood disease, affecting 334 million people worldwide, it is important for out-of-hospital professionals to stay up to date with current guidelines to be able to optimally manage exacerbations in these illnesses. 5,6 Adults and children have significant differences in airway anatomy and physiology, particularly in infants < 1 year of age. 4 Airway diameter in a pediatric patient is considerably smaller than in an adult, thus any narrowing heightens concern for obstruction. 4 Upper airway causes of pediatric respiratory distress produce noise during inspiration, called stertor or stridor, depending on the location of the problem. 4,7 Stridor results from sounds originating from the larynx and trachea. Causes of stridor on pediatric patients may include croup, anaphylaxis, or foreign body aspiration. 7 Croup or laryngotracheobronchitis is the most common cause of acute stridor in childhood, responsible for 15% of pediatric respiratory visits to the emergency department (ED). 8 It is caused by inflammation in the upper airways usually caused by viruses, occurring most frequently in the fall and winter. In addition to stridor, a classic "barking cough" can also be appreciated in croup, particularly in infants and small children. 7 Lower airway causes of pediatric respiratory distress produce noises during expiration, called wheezes, rhonchi, or rales, depending on the location and type of problem. 5,9 Children have more smooth muscle throughout their airways, making them more sensitive to inflammation caused by foreign substances and infections. 4 Wheezing in children has multiple etiologies including bronchiolitis (in children < 24 months), asthma, cardiac conditions, and foreign body aspiration, the first 2 being the most common. 9 Bronchiolitis is a seasonal illness, occurring mostly in the fall and winter months. 10 This is a lung condition typically caused by a viral infection, such as respiratory syn-cytial virus (RSV) or rhinovirus. It affects the lower, smaller portions of the airway known as bronchioles causing retractions and coarse lung sounds. Children often demonstrate upper airway symptoms, such as rhinorrhea, together with lower airway infection and inflammation, causing appreciable wheezes and/or crackles. This can lead to profound dehydration and respiratory failure. 10 ED management of the most common pediatric respiratory distress presentations, such as stridor and wheezing, has evolved over time, but it is unknown if out-of-hospital protocol changes have progressed at the same pace. Out-of-hospital protocols and treatment recommendations for pediatric respiratory distress vary widely across California. This study focuses on the most common etiologies of stridor and wheezing. Our 2 objectives were first to develop evidence-based recommendations for the out-of-hospital treatment of 3 main pediatric respiratory complaints by symptom presentation: stridor (croup), wheezing in children < 24 months (bronchiolitis), and wheezing in children 2 years and older (asthma), and second to evaluate the current protocols for pediatric respiratory distress used by the 33 EMS agencies in California. have performed systematic reviews and meta-analyses regarding treatment interventions. 10 Given that no articles were found in PubMed searching for "prehospital and pediatric respiratory distress,"

EMS systems in
our review was supplemented with more general search terms including many emergency department-and hospital-based studies. The broader literature search concluded in January 2019 and included search terms such as "croup treatment," "pediatric wheezing treatment," and "bronchiolitis management." The grading of recommendations assessment, development and evaluation (GRADE) methodology was used to evaluate our literature.
We assigned levels of evidence and categorized our recommendations Using the assigned levels of evidence of each study, recommendations were made using the following standards.

Level A recommendations
• Out-of-hospital recommendations with a strong degree of certainty based on 1 or more levels of evidence I studies or multiple levels of evidence II studies.

Level B recommendations
• Out-of-hospital recommendations with a moderate degree of certainty based on 1 or more levels of evidence II studies or multiple levels of evidence III studies.

Level C recommendations
• Out-of-hospital recommendations based on only poor quality or minimal levels of evidence III studies or based on consensus.

No recommendation
• No recommendation was given in those cases where only preliminary data or no published evidence exists, and we had no expert consensus.
• We also withheld recommendation when studies, no matter their levels of evidence, showed conflicting data.
In March 2016, 2 authors comparatively reviewed the current pediatric respiratory distress protocol from the 33 agencies (Table   1). The focus of this review was the management of the following categories of pediatric respiratory distress: stridor (croup), wheezing < 24 months (bronchiolitis), and wheezing (asthma). The protocols were then compared to the evidence-based tables, carefully examining the treatment versus its level of evidence, and thus, recommendation level ( Table 2). Descriptive statistics were used to compare these protocols.

The Bottom Line
Emergency medical service protocols vary widely for the outof-hospital management of stridor in the setting of croup and wheezing with bronchiolitis in young children. This variation is an opportunity for practice improvement to improve outcomes in young children with respiratory distress.

Clinical question
How should EMS professionals treat pediatric respiratory distress with stridor (croup)?  This local EMS agency has Mg protocols for Adult respiratory distress, but no specific guidelines for pediatrics.

Summary of current evidence
therapy is ineffective for improving respiratory distress in pediatric patients with croup. [16][17][18] No studies were found specifically examining parenteral (intravenous or intramuscular) epinephrine use in pediatric patients with stridor or croup. In regard to treatment with noninvasive positive pressure ventilation, 1 small nonrandomized trial focusing on children with chronic stridor from laryngomalacia identified that noninvasive positive pressure ventilation was well tolerated and improved work of breathing. 19 Given this population is unique compared to the general out-of-hospital population with acute stridor, conclusions cannot be made from this study on whether noninvasive positive pressure ventilation would help in all cases of acute stridor.

Current out-of-hospital treatment recommendation
Level A recommendation • Treatment with nebulized epinephrine should be initiated in children with stridor and respiratory distress.
• Treatment with steroids should be initiated in patients with suspected croup.
• Treatment with mist therapy does not show any benefit.

Level B recommendation
• Not given.

Level C recommendation
• Not given.

No recommendation
• Treatment with noninvasive positive pressure ventilation.
• Treatment with IV/IM epinephrine.

Clinical question
What is the treatment indicated for pediatric respiratory distress with wheezing in children < 24 months old (bronchiolitis)?

Current out-of-hospital treatment recommendation
Level A recommendation • Treatment with nebulized albuterol has not been proven beneficial in the previously healthy patient with bronchiolitis.
• Treatment with noninvasive positive pressure ventilation should be initiated.

Level B recommendation
• Treatment with suctioning should be initiated.

Level C recommendation
• Not given.

Clinical question
How should EMS professionals treat pediatric respiratory distress with wheezing (asthma)?

Summary of the current evidence
Recommendations based on current evidence supports the use of albuterol, ipratropium, magnesium, steroids, and noninvasive positive pressure ventilation in a child with an acute asthma exacerbation. There is strong evidence in the literature for albuterol use on pediatric patients in respiratory distress with known asthma in the ED 23,[31][32][33][34] ; however, the out-of-hospital literature is limited. Some outof-hospital studies show improvement in dyspnea with the use of betaagonists like albuterol. [35][36][37] One small study showed that basic life sup-port (BLS) professionals could successfully administer nebulized betaagonists in children. 37 Multiple studies have shown that in severe asthma exacerbations in children, ipratropium use in the emergency setting reduced hospital admission rates and improved pulmonary function tests with no increase in adverse effects. [38][39][40][41][42][43] Studies on out-of-hospital use of ipratropium are limited to adults, with 1 small retrospective cohort study showing no differences before and after the addition of ipratropium to an out-of-hospital protocol. 44 Treatment with intravenous magnesium sulfate shows improvement in multiple randomized control trials when given intravenously during an acute asthma exacerbation. [45][46][47][48][49] A metaanalyses with a total of 859 pediatric patients given magnesium sulfate in the ED for acute bronchospasm showed some improved and no serious adverse events. 45 One Cochrane Review involving 665 patients (including 2 pediatric trials) who received magnesium sulfate in the ED for acute asthma found that for patients with severe asthma, peak flow rates improved and hospital admission rates were reduced. 46 Of note, inhaled magnesium sulfate has inconclusive results with a Cochrane Review of 6 trials showing no improvement in outcomes. 50 Evidence for steroid administration in the ED for a pediatric patient during a moderate to severe asthma exacerbation is strong, and many studies suggest early administration for the best outcomes. [51][52][53][54][55][56][57][58][59] Current literature for out-of-hospital steroid administration in pediatric asthma exacerbations is limited; however, 1 small retrospective cohort study showed that after addition of out-of-hospital-administered oral dexamethasone to their asthma protocol, asthmatic children who received out-of-hospital steroids had shorter total hospital and total care times, decreased hospitalization rates, and less need for critical care. 60 Multiple studies showed that noninvasive positive pressure ventilation use in asthmatic children decreased work of breathing and improved oxygenation, reducing intubation rates. [61][62][63][64][65] Therefore, noninvasive positive pressure ventilation should be used prior to intubation in children with severe asthma exacerbations.
Intravenous and intramuscular epinephrine use in asthma is not well studied. Two randomized control trials showed no difference in clinical scores, pulmonary function, or admission rates between patients who received albuterol alone and patients who received subcutaneous epinephrine. 66,67 One retrospective chart review showed epinephrine used in acute life-threatening asthma was safe in patients 19-58 years of age. 68 Given the limited evidence, epinephrine is recommended for use, in addition to albuterol, only in asthmatic children with impending respiratory failure.

Current out-of-hospital treatment recommendation
Level A recommendation • Treatment with albuterol nebulized or by metered dose inhaler (MDI) should be initiated in all children in respiratory distress with signs of bronchospasm.
• Treatment with nebulized ipratropium should be initiated in moderate to severe asthma exacerbations.
• Treatment with intravenous magnesium should be initiated in severe asthma exacerbations.
• Treatment with steroids should be initiated early.
• Treatment with noninvasive positive pressure ventilation should be initiated in patients with severe asthma exacerbation.

Level B recommendation
• Not given.

Level C recommendation
• Treatment with intravenous or intramuscular epinephrine is indicated in addition to albuterol in acutely asthmatic children with impending respiratory failure only.

Protocol review
Protocols from all 33 California local EMS agencies were reviewed for consistency and variability (Table 1). These were compared with recommendations for out-of-hospital respiratory distress management developed from the literature review (

Pediatric stridor (croup) treatment
Stridor had the highest protocol variability of the 3 presentations we evaluated, with no treatment having uniform use among all agencies. The most common treatments included IV/IM epinephrine (24/33), noninvasive positive pressure ventilation (29/33), and humidified mist (18/33). The least common treatments were nebulized epinephrine (12/33) and suctioning (4/33). California local EMS agency protocols did not have stridor in the same categories. Some included stridor under "foreign body aspiration," others in "anaphylaxis" and some listed it as its own separate entity. Rarely was stridor listed under a specific "croup" protocol.

Pediatric wheezing < 24 months (bronchiolitis) treatment
Three (9.1%) of the local EMSs agencies differentiated wheezing in children < 24 months of age, referencing this as possible bronchiolitis. All 3 included albuterol and noninvasive positive pressure ventilation as their recommended treatments. None of these included suctioning as part of their treatments.

Pediatric wheezing (asthma) treatment
All local EMS included albuterol and epinephrine (intravenous/ intramuscular) in their pediatric wheezing treatment protocols. The least common treatments included nebulized epinephrine (3/33) and magnesium (2/33). Ipratropium is included in less than half of the California local EMS agency protocols (15/33). The majority include noninvasive positive pressure ventilation in their treatment protocol (32/33). No agencies included steroids in their treatment protocol (0/33). Only 2 of the 6 treatments, ipratropium (15/33) and nebulized epinephrine (3/33), had > 2 local EMS agencies with significant differences in recommended management.

LIMITATIONS
These evidenced-based recommendations, as well as the protocol review, do not include all possible etiologies of stridor and wheezing in the pediatric patient, but instead they are focused on the most common diagnoses causing these symptoms. Only the protocols within the state of California were evaluated. This may limit the generalizability.

DISCUSSION
Pediatric stridor protocols had the highest variability of the 3 presentations we evaluated, with no treatment having uniform use among all agencies. Given that stridor was rarely listed under a specific "croup" protocol, this is possibly why the management of stridor varies greatly amongst local emergency medical services agencies. It may be beneficial to specify, and thus itemize, different management practices for all of the various causes of stridor. In the out-of-hospital setting, it can be very difficult to quickly identify the exact cause for audible stridor.
However, designing a protocol that describes the specific features of a foreign body aspiration versus an allergic/inflammatory reaction (anaphylaxis) versus an infectious disease (croup and epiglottitis) could assist the out-of-hospital professional in selecting the most appropriate treatment. For example, treatment with racemic epinephrine would be indicated in both croup and anaphylaxis.
In most recent years, the AAP has adjusted its recommendations for treating bronchiolitis. 10 Currently, it is not advised to provide albuterol or steroids. Rather, treatment is more supportive in nature, promoting nasal suctioning, supplemental oxygen, and positive pressure ventilation when needed. 10 It is important for out-of-hospital professionals to be educated and trained on nasal suctioning for infants, as this supportive treatment can considerably improve the patient's respiratory distress. Many would agree that recognizing wheezing in young children as secondary to bronchiolitis and not to asthma, and thus treating them differently, is challenging. Thus, timely educational updates to out-of-hospital personnel informing them of these changes in guidelines are essential. Although albuterol is a very common medication, it is not without its own risks and side effects. 20,23,26 As well, the notion of tunnel-visioning on a single diagnosis, that is, asthma, in the presence of pediatric wheezing is also problematic, particularly when the professional's assumed treatment of choice (ie, albuterol) is not effective in managing the disease. It is important that if albuterol is chosen as a treatment modality, documenting its use and whether it changed the patient's respiratory status is helpful for the ED staff taking over care. Highlighting the uniqueness of bronchiolitis, in both pathology and treatment, could greatly benefit out-of-hospital care and ideally would be represented in each local EMS agency's respective protocols.
Generally, asthma (wheezing) treatment protocols aligned well with the current evidence found in our literature review. However, despite the evidence for use in pediatric asthma exacerbations, ipratropium use was in less than half of the local EMS agencies (15/33). This may be due to the narrow temperature storage window for ipratropium (36 • F-77 • F) and previous studies showing that many out-of-hospital medications show temperature-dependent degradation. 69,70 Magnesium and steroids were not included in any pediatric wheezing protocols. Magnesium use was included in 3 local EMS agency adult respiratory distress protocols but not in their pediatric protocols.
Although croup, bronchiolitis, and asthma are not exclusive causes of pediatric stridor, wheezing in < 24 months, and wheezing in ≥ 24 months, respectively, these are the most common diagnoses; thus, EMS pediatric protocols for these symptoms should reflect their specific treatments. EMS education, however, should still focus on differential diagnosis and a stepwise approach treatment of a child in respiratory distress. Pediatric respiratory distress protocols vary greatly in content and structure in California, especially among those for stridor (or croup) and wheezing in < 24 months (bronchiolitis). Pediatric stridor (or croup) not only had the highest protocol variability of the 3 presentations we evaluated, but it also had the most treatment deviations from the current evidence. Recent changes to treatment guidelines have likely created the discordance between current treatment practices and our evidence-based recommendations. Due to the limited number of out-of-hospital pediatric respiratory distress treatment studies, many ED-based studies facilitated the creation of these recommendations. The evidence-based recommendations presented in this study may be useful to EMS medical directors for the creation and revision of EMS protocols for the out-of-hospital treatment of pediatric respiratory distress.

CONFLICT OF INTEREST
The authors declare no conflict of interest.