Affiliations
Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
Given name(s)
Brian M.
Family name
Pate
Degrees
MD

Bronchiolitis and Discharge Criteria

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Hospital course and discharge criteria for children hospitalized with bronchiolitis

Although bronchiolitis is the leading cause of hospitalization for US infants,[1] there is a lack of basic prospective data about the expected inpatient clinical course and ongoing uncertainty about when a hospitalized child is ready for discharge to home.[2] This lack of data about children's readiness for discharge may result in variable hospital length‐of‐stay (LOS).[3, 4, 5]

One specific source of variability in discharge readiness and LOS variability may be the lack of consensus about safe threshold oxygen saturation values for discharge in children hospitalized with bronchiolitis.[6, 7] In 2006, the Scottish Intercollegiate Guidelines Network recommended a discharge room air oxygen (RAO2) saturation threshold of 95%.[8] The same year, the American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline stated that oxygen is not needed for children with RAO2 saturations 90% who are feeding well and have minimal respiratory distress.[9] There is a need for prospective studies to help clinicians make evidenced‐based discharge decisions for this common condition.

We performed a prospective, multicenter, multiyear study[10, 11, 12] to examine the typical inpatient clinical course of and to develop hospital discharge guidelines for children age <2 years hospitalized with bronchiolitis. We hypothesized that children would not worsen clinically and would be safe to discharge home once their respiratory status improved and they were able to remain hydrated.

METHODS

Study Design and Population

We conducted a prospective, multicenter cohort study for 3 consecutive years during the 2007 to 2010 winter seasons, as part of the Multicenter Airway Research Collaboration (MARC), a program of the Emergency Medicine Network (www.emnet‐usa.org). The number of participating sites varied over the 3 years: 13 in year 1, 16 in year 2, and 14 in year 3. Each month from November 1 until March 31, site investigators across 12 US states used a standardized protocol to enroll a target number of consecutive patients from the inpatient wards and the intensive care unit (ICU). We aimed to enroll 20% of our total sample from the ICU. To over sample children in the ICU, the ward and ICU enrollments were separate. Once the site reached their target enrollment for that month, the investigators would stop enrollment until the beginning of the following month.

All patients were treated at the discretion of the treating physician. Inclusion criteria were an attending physician's diagnosis of bronchiolitis, age <2 years, and the ability of the parent/guardian to give informed consent. The exclusion criteria were previous enrollment and transfer to a participating hospital >48 hours after the original admission time. Therefore, children with comorbid conditions were included in this study. All consent and data forms were translated into Spanish. The institutional review board at each of the 16 participating hospitals approved the study.

Of the 2207 enrolled children, we excluded 109 (5%) children with a hospital LOS <1 day due to inadequate time to capture the required data for the present analysis. Among the 2098 remaining children, 1916 (91%) had daily inpatient data on all factors used to define clinical improvement and clinical worsening. Thus, the analytic cohort was comprised of 1916 children hospitalized for bronchiolitis.

Data Collection

Investigators conducted detailed structured interviews. Chart reviews were conducted to obtain preadmission and daily hospital clinical data including respiratory rates, daily respiratory rate trends, degree of retractions, oxygen saturation, daily oxygen saturation trends, medical management, and disposition. These data were manually reviewed, and site investigators were queried about missing data and discrepancies. A follow‐up telephone interview was conducted with families 1 week after discharge to examine relapse events at both 24 hours and 7 days.

We used the question: How long ago did the following symptoms [eg, difficulty breathing] begin [for the] current illness? to estimate the onset of the current illness. Pulse was categorized as low, normal, or high based on age‐related heart rate values.[13] Presence of apnea was recorded daily by site investigators.[14]

Nasopharyngeal Aspirate Collection and Virology Testing

As described previously, site teams used a standardized protocol to collect nasopharyngeal aspirates,[11] which were tested for respiratory syncytial virus (RSV) types A and B; rhinovirus (RV); parainfluenza virus types 1, 2, and 3; influenza virus types A and B; 2009 novel H1N1; human metapneumovirus; coronaviruses NL‐63, HKU1, OC43, and 229E; enterovirus, and adenovirus using polymerase chain reaction.[11, 15, 16, 17]

Defining Clinical Improvement and Worsening

Clinical improvement criteria were based on the 2006 AAP guidelines.[9] For respiratory rate and oxygen saturation, clinicians estimated average daily respiratory rate and oxygen saturation based on the recorded readings from the previous 24 hours. This estimation reflects the process clinicians use when rounding on their hospitalized patients, and thus may be more similar to standard clinical practice than a calculated mean. The respiratory rate criteria are adjusted for age.[18, 19] For daily estimated average oxygen saturation we used the AAP criteria of RAO2 saturation of 90%. Considering that oxygen saturation is the main determinant of LOS,[20] healthy infants age <6 months may have transient oxygen saturations of around 80%,[21] and that errors in estimation may occur, we included a lowest RAO2 of 88% in our improvement criteria. By combining the dichotomized estimated oxygen saturation (90% or not) with the lower limit of 88%, there was little room for erroneous conclusions. A child was considered clinically improved on the earliest date he/she met all of the following criteria: (1) none or mild retractions and improved or stable retractions compared with the previous inpatient day; (2) daily estimated average respiratory rate (RR) <60 breaths per minute for age <6 months, <55 breaths/minute for age 6 to 11 months, and <45 breaths/minute for age 12 months with a decreasing or stable trend over the course of the current day; (3) daily estimated average RAO2 saturation 90%, lowest RAO2 saturation 88%[21]; and (4) not receiving intravenous (IV) fluids or for children receiving IV fluids a clinician report of the child maintaining oral hydration. Children who reached the clinical improvement criteria were considered clinically worse if they required intensive care or had the inverse of 1 of the improvement criteria: moderate/severe retractions that were worse compared with the previous inpatient day, daily average RR 60 with an increasing trend over the current day, need for oxygen, or need for IV fluids.

Statistical Analyses

All analyses were performed using Stata 12.0 (StataCorp, College Station, TX). Data are presented as proportions with 95% confidence intervals (95% CIs), means with standard deviations, and medians with interquartile ranges (IQR). To examine potential factors associated with clinical worsening after reaching clinical improvement, we used 2, Fisher exact, Student t test, and Kruskall‐Wallis tests, as appropriate.

Adjusted analyses used generalized linear mixed models with a logit link to identify independent risk factors for worsening after reaching clinical improvement. Fixed effects for patient‐level factors and a random site effect were used. Factors were tested for inclusion in the multivariable model if they were found to be associated with worsening in unadjusted analyses (P<0.20) or were considered clinically important. Results are reported as odds ratios with 95% CIs.

We performed several sensitivity analyses to evaluate these improvement criteria: (1) we excluded the lowest RAO2 saturation requirement of 88%, (2) we examined a 94% daily estimated average RAO2 saturation threshold,[22] (3) we examined a 95% daily estimated average RAO2 saturation threshold,[8] and (4) we examined children age <12 months with no history of wheeze.

RESULTS

There were 1916 children hospitalized with bronchiolitis with data on all factors used to define clinical improvement and clinical worsening. The median number of days from the beginning of difficulty breathing until admission was 2 days (IQR, 15.5 days; range, 18 days) and from the beginning of difficulty breathing until clinical improvement was 4 days (IQR, 37.5 days; range, 133 days) (Figure 1). The variance for days to admission was significantly less than the variance for days to clinical improvement (P<0.001).

Figure 1
Time course of illness for children hospitalized with bronchiolitis.

In this observational study, clinicians discharged 214 (11%) of the 1916 children before meeting the definition of clinical improvement. Thus, 1702 (89%; 95% CI: 87%‐90%) children reached the clinical improvement criteria, had a LOS >1 day, and had data on all factors (Figure 2).

Figure 2
Flow diagram of the study population. *Eight children were worsened on more than 1 criterion. Abbreviations: ICU, intensive care unit; IV, intravenous; LOS, length of stay; RR, respiratory rate.

Of the 1702 children who met the clinical improvement criteria, there were 76 children (4%; 95% CI: 3%5%) who worsened (Figure 2). The worsening occurred within a median of 1 day (IQR, 13 days) of clinical improvement. Forty‐six (3%) of the children required transfer to the ICU (1 required intubation, 1 required continuous positive airway pressure, and 4 had apnea), 23 (1%) required oxygen, and 17 (1%) required IV fluids. Eight percent of children met multiple criteria for worsening. A comparison between children who did and did not worsen is shown in Table 1. In general, children who worsened after improvement were younger and born earlier. These children also presented in more severe respiratory distress, had moderate or severe retractions, oxygen saturation <85% at hospitalization, inadequate oral intake, and apnea documented during the hospitalization. Neither viral etiology nor site of care influenced whether the children worsened after improving. However, stratified analysis of children based on initial location of admission (ie, ICU or ward) showed that among the children admitted to the ICU from the emergency department (ED), 89% met the improvement criteria and 19% clinically worsened. In contrast, among children admitted to the ward from the ED, 89% met the improvement criteria, and only 2% clinically worsened. Stratified multivariable models based on the initial location of admission from the ED (ie, ICU or ward) were not possible due to small sample sizes after stratification. None of these children had relapse events requiring rehospitalization within either 24 hours or 7 days of discharge.

Characteristics of Children Who Did Not Worsen Versus Those Who Worsened After Clinical Improvement
 Did Not Worsen, n=1,626Worsened, n=76P Value
  • NOTE: Abbreviations: ABG, arterial blood gas; ED, emergency department; HRV, human rhinovirus; IQR, interquartile range; RSV, respiratory syncytial virus.

Demographic characteristics   
Age <2 months, %2957<0.001
Month of birth, %  0.02
OctoberMarch6175 
AprilSeptember3925 
Sex, %  0.51
Male5955 
Female4145 
Race, %  0.050
White6358 
Black2334 
Other or missing148 
Hispanic ethnicity, %37220.01
Insurance, %  0.87
Nonprivate6867 
Private3233 
Medical history   
Gestational age <37 weeks, %23390.002
Birth weight, %  0.52
<5 lbs1312 
5 lbs3441 
7 lbs5347 
Mother's age, median (IQR)27 (2333)27 (2233)0.54
Is or was breastfed, %61510.10
Smoked during pregnancy, %15200.22
Exposure to smoke, %13200.11
Family history of asthma, %  0.89
Neither parent6864 
Either mother or father2730 
Both parents44 
Do not know/missing21 
History of wheezing, %23170.24
History of eczema, %1670.04
History of intubation, %9120.50
Major, relevant, comorbid medical disorder, %20240.46
Current illness   
When difficulty breathing began, preadmission, %0.63
1 day7075 
<1 day2823 
No difficulty preadmission23 
Weight, lbs, median (IQR)12.3 (8.817.4)9.0 (6.613.2)0.001
Temperature, F, median (IQR)99.5 (98.6100.6)99.4 (98.1100.4)0.06
Pulse, beats per minute by age  0.82
Low0.30 
Normal4846 
High5154 
Respiratory rate, breaths per minute, median (IQR)48 (4060)48 (3864)0.28
Retractions, %  0.001
None2225 
Mild4324 
Moderate2633 
Severe412 
Missing57 
Oxygen saturation by pulse oximetry or ABG, %0.001
<85412 
8587.934 
8889.950 
9093.91811 
947273 
Oral intake, %  <0.001
Adequate4522 
Inadequate4263 
Missing1314 
Presence of apnea, %724<0.001
RSV‐A, %44410.54
RSV‐B, %30250.36
HRV, %24240.88
Chest x‐ray results during ED/preadmission visit
Atelectasis12130.77
Infiltrate13110.50
Hyperinflated18210.47
Peribronchial cuffing/thickening23170.32
Normal14160.75
White blood count, median (IQR)11.2 (8.714.4)11.9 (9.214.4)0.60
Platelet count, median (IQR)395 (317490)430 (299537)0.56
Sodium, median (IQR)138 (136140)137 (135138)0.19
Hospital length of stay, median (IQR)2 (14)4.5 (28)<0.001
One‐week follow‐up   
Relapse within 24 hours of hospital discharge requiring hospital admission, %0.500.56
Relapse within 7 days of hospital discharge requiring hospital admission, %100.35

On multivariable analysis (Table 2), independent risk factors for worsening after reaching the clinical improvement criteria were young age, preterm birth, and presenting to care with more severe bronchiolitis represented by severe retractions, inadequate oral intake, or apnea. To further evaluate the improvement criteria in the current analysis, multiple sensitivity analyses were conducted. The frequency of clinical worsening after reaching the improvement criteria was stable when we examined different RA02 criteria in sensitivity analyses: (1) excluding RA02 as a criterion for improvement: 90% met improvement criteria and 4% experienced clinical worsening, (2) changing the average RA02 threshold for clinical improvement to 94%: 62% met improvement criteria and 6% experienced clinical worsening, and (3) changing the average RA02 threshold for clinical improvement to 95%: 47% met improvement criteria and 5% experienced clinical worsening. Furthermore, stratifying by age <2 months and restricting to more stringent definitions of bronchiolitis (ie, age <1 year or age <1 year+no history of wheezing) also did not materially change the results (see Supporting Figure 1 in the online version of this article).

Multivariable Model of Factors Associated With a Worsening of Symptoms After Clinical Improvement.
 Odds Ratio95% CIP Value
  • NOTE: Abbreviations: CI, confidence interval.

Age <2 months3.512.07‐5.94<0.001
Gestational age <37 weeks1.941.13‐3.320.02
Retractions   
None1.300.80‐3.230.19
Mild1.0Reference 
Moderate1.910.99‐3.710.06
Severe5.552.1214.50<0.001
Missing1.700.53‐5.420.37
Oral intake   
Adequate1.00Reference 
Inadequate2.541.39‐4.620.002
Unknown/missing1.880.79‐4.440.15
Presence of apnea2.871.45‐5.680.003

We compared the 214 children who were discharged prior to reaching clinical improvement with the 1702 children who reached the clinical improvement criteria. The 214 children were less likely to be age <2 months (22% vs 30%; P=0.02). These 2 groups (214 vs 1702) were similar with respect to severe retractions (2% vs 4%; P=0.13), median respiratory rate (48 vs 48; P=0.42), oxygen saturation <90% (15% vs 11%; P=0.07), inadequate oral intake (50% vs 43%; P=0.13), and rates of relapse events requiring rehospitalization within both 24 hours (0.6% vs 0.6%; P=0.88) and 7 days (1% vs 1%; P=0.90) of discharge.

DISCUSSION

In this large, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that children present to a hospital in a relatively narrow time frame, but their time to recovery in the hospital is highly variable. Nonetheless, 96% of children continued to improve once they had: (1) improving or stable retractions rated as none/mild, (2) a decreasing or stable RR by age, (3) estimated average RAO2 saturation 90% and lowest RAO2 saturation of 88%, and (4) were hydrated. The 4% of children who worsened after clinically improving were more likely to be age <2 months, born <37 weeks, and present with more severe distress (ie, severe retractions, inadequate oral intake, or apnea). Based on the low risk of worsening after clinical improvement, especially among children admitted to the regular ward (2%), we believe these 4 clinical criteria could be used as discharge criteria for this common pediatric illness with a predominantly monophasic clinical course.

Variability in hospital LOS for children with bronchiolitis exists in the United States[3] and internationally.[4, 5] Cheung and colleagues analyzed administrative data from over 75,000 children admitted for bronchiolitis in England between April 2007 and March 2010 and found sixfold variation in LOS between sites. They concluded that this LOS variability was due in part to providers' clinical decision making.[5] Srivastava and colleagues[23] addressed variable clinician decision making in bronchiolitis and 10 other common pediatric conditions by embedding discharge criteria developed by expert consensus into admission order sets. They found that for children with bronchiolitis, the embedded discharge criteria reduced the median LOS from 1.91 to 1.87 days. In contrast to the single‐center data presented by White and colleagues,[24] the prospective, multicenter MARC‐30 data provide a clear understanding of the normal clinical course for children hospitalized with bronchiolitis, determine if children clinically worsen after clinical improvement, and provide data about discharge criteria for children hospitalized with bronchiolitis. Although there is a lack of rigorous published data, the lower tract symptoms of bronchiolitis (eg, cough, retractions) are said to peak on days 5 to 7 of illness and then gradually resolve.[25] In the present study, we found that the time from the onset of difficulty breathing until hospital admission is less variable than the time from the onset of difficulty breathing until either clinical improvement or discharge. Although 75% of children have clinically improved within 7.5 days of difficulty breathing based on the IQR results, the remaining 25% may have a more prolonged recovery in the hospital of up to 3 weeks. Interestingly, prolonged recovery times from bronchiolitis have also been noted in children presenting to the ED[26] and in an outpatient population.[27] It is unclear why 20% to 25% of children at different levels of severity of illness have prolonged recovery from bronchiolitis, but this group of children requires further investigation.

Given the variability of recovery times, clinicians may have difficulty knowing when a child is ready for hospital discharge. One of the main stumbling blocks for discharge readiness in children with bronchiolitis is the interpretation of the oxygen saturation value.[6, 8, 9, 20, 28] However, it should be considered that interpreting the oxygen saturation in a child who is clinically improving in the hospital setting is different than interpreting the oxygen saturation of a child in the ED or the clinic whose clinical course is less certain.[22] In the hospital setting, using the oxygen saturation value in in the AAP guideline,[9] 4% of children clinically worsened after they met the improvement criteria, a clinical pattern observed previously with supplemental oxygen.[28] This unpredictability may explain some of the variation in providers' clinical decision making.[5] The children who worsened, and therefore deserve more cautious discharge planning, were young (<2 months), premature (<37 weeks gestational age), and presented in more severe distress. Those children admitted to the ICU from the ED worsened more commonly than children admitted to the ward (19% vs 2%). Interestingly, the viral etiology of the child's bronchiolitis did not influence whether a child worsened after reaching the improvement criteria. Therefore, although children with RV bronchiolitis have a shorter hospital LOS than children with RSV bronchiolitis,[11] the pattern of recovery did not differ by viral etiology.

In addition to unsafe discharges, clinicians may be concerned about the possibility of readmissions. Although somewhat controversial, hospital readmission is being used as a quality of care metric.[29, 30, 31] One response to minimize readmissions would be for clinicians to observe children for longer than clinically indicated.[32] However, shorter LOS is not necessarily associated with increased readmission rates.[33] Given that the geometric mean of hospital charges per child with bronchiolitis increased from $6380 in 2000 to $8530 in 2009,[34] the potential for safely reducing hospital LOS by using the discharge criteria proposed in the current study instead of other criteria[8] may net substantial cost savings. Furthermore, reducing LOS would decrease the time children expose others to these respiratory viruses and possibly reduce medical errors.[35]

Our study has some potential limitations. Because the study participants were all hospitalized, these data do not inform admission or discharge decisions from either the ED or the clinic; but other data address those clinical scenarios.[22] Also, the 16 sites that participated in this study were large, urban teaching hospitals. Consequently, these results are not necessarily generalizable to smaller community hospitals. Although numerous data points were required to enter the analytic cohort, only 9% of the sample was excluded for missing data. There were 214 children who did not meet our improvement criteria by the time of discharge. Although the inability to include these children in the analysis may be seen as a limitation, this practice variability underscores the need for more data about discharging hospitalized children with bronchiolitis. Last, site teams reviewed medical records daily. More frequent recording of the clinical course would have yielded more granular data, but the current methodology replicates how data are generally presented during patient care rounds, when decisions about suitability for discharge are often considered.

CONCLUSION

We documented in this large multicenter study that most children hospitalized with bronchiolitis had a wide range of time to recovery, but the vast majority continued to improve once they reached the identified clinical criteria that predict a safe discharge to home. The children who worsened after clinical improvement were more likely to be younger, premature infants presenting in more severe distress. Although additional prospective validation of these hospital discharge criteria is warranted, these data may help clinicians make more evidence‐based discharge decisions for a common pediatric illness with high practice variation, both in the United States[3] and in other countries.[4, 5]

Acknowledgements

Collaborators in the MARC‐30 Study: Besh Barcega, MD, Loma Linda University Children's Hospital, Loma Linda, CA; John Cheng, MD, Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Dorothy Damore, MD, New York Presbyterian Hospital‐Cornell, New York, NY; Carlos Delgado, MD, Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Haitham Haddad, MD, Rainbow Babies & Children's Hospital, Cleveland, OH; Paul Hain, MD, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN; Frank LoVecchio, DO, Maricopa Medical Center, Phoenix, AZ; Charles Macias, MD MPH, Texas Children's Hospital, Houston, TX; Jonathan Mansbach, MD, MPH, Boston Children's Hospital, Boston, MA; Eugene Mowad, MD, Akron Children's Hospital, Akron, OH; Brian Pate, MD, Children's Mercy Hospital, Kansas City, MO; Mark Riederer, MD, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN; M. Jason Sanders, MD, Children's Memorial Hermann Hospital, Houston, TX; Alan R. Schroeder, MD, Santa Clara Valley Medical Center, San Jose, CA; Nikhil Shah, MD, New York Presbyterian Hospital‐Cornell, New York, NY; Michelle Stevenson, MD, MS, Kosair Children's Hospital, Louisville, KY; Erin Stucky Fisher, MD, Rady Children's Hospital, San Diego, CA; Stephen Teach, MD, MPH, Children's National Medical Center, Washington, DC; Lisa Zaoutis, MD, Children's Hospital of Philadelphia, Philadelphia, PA.

Disclosures: This study was supported by grants U01 AI‐67693 and K23 AI‐77801 from the National Institutes of Health (Bethesda, MD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Drs. Mansbach and Piedra have provided consultation to Regeneron Pharmaceuticals. Otherwise, no authors report any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations.

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References
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Although bronchiolitis is the leading cause of hospitalization for US infants,[1] there is a lack of basic prospective data about the expected inpatient clinical course and ongoing uncertainty about when a hospitalized child is ready for discharge to home.[2] This lack of data about children's readiness for discharge may result in variable hospital length‐of‐stay (LOS).[3, 4, 5]

One specific source of variability in discharge readiness and LOS variability may be the lack of consensus about safe threshold oxygen saturation values for discharge in children hospitalized with bronchiolitis.[6, 7] In 2006, the Scottish Intercollegiate Guidelines Network recommended a discharge room air oxygen (RAO2) saturation threshold of 95%.[8] The same year, the American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline stated that oxygen is not needed for children with RAO2 saturations 90% who are feeding well and have minimal respiratory distress.[9] There is a need for prospective studies to help clinicians make evidenced‐based discharge decisions for this common condition.

We performed a prospective, multicenter, multiyear study[10, 11, 12] to examine the typical inpatient clinical course of and to develop hospital discharge guidelines for children age <2 years hospitalized with bronchiolitis. We hypothesized that children would not worsen clinically and would be safe to discharge home once their respiratory status improved and they were able to remain hydrated.

METHODS

Study Design and Population

We conducted a prospective, multicenter cohort study for 3 consecutive years during the 2007 to 2010 winter seasons, as part of the Multicenter Airway Research Collaboration (MARC), a program of the Emergency Medicine Network (www.emnet‐usa.org). The number of participating sites varied over the 3 years: 13 in year 1, 16 in year 2, and 14 in year 3. Each month from November 1 until March 31, site investigators across 12 US states used a standardized protocol to enroll a target number of consecutive patients from the inpatient wards and the intensive care unit (ICU). We aimed to enroll 20% of our total sample from the ICU. To over sample children in the ICU, the ward and ICU enrollments were separate. Once the site reached their target enrollment for that month, the investigators would stop enrollment until the beginning of the following month.

All patients were treated at the discretion of the treating physician. Inclusion criteria were an attending physician's diagnosis of bronchiolitis, age <2 years, and the ability of the parent/guardian to give informed consent. The exclusion criteria were previous enrollment and transfer to a participating hospital >48 hours after the original admission time. Therefore, children with comorbid conditions were included in this study. All consent and data forms were translated into Spanish. The institutional review board at each of the 16 participating hospitals approved the study.

Of the 2207 enrolled children, we excluded 109 (5%) children with a hospital LOS <1 day due to inadequate time to capture the required data for the present analysis. Among the 2098 remaining children, 1916 (91%) had daily inpatient data on all factors used to define clinical improvement and clinical worsening. Thus, the analytic cohort was comprised of 1916 children hospitalized for bronchiolitis.

Data Collection

Investigators conducted detailed structured interviews. Chart reviews were conducted to obtain preadmission and daily hospital clinical data including respiratory rates, daily respiratory rate trends, degree of retractions, oxygen saturation, daily oxygen saturation trends, medical management, and disposition. These data were manually reviewed, and site investigators were queried about missing data and discrepancies. A follow‐up telephone interview was conducted with families 1 week after discharge to examine relapse events at both 24 hours and 7 days.

We used the question: How long ago did the following symptoms [eg, difficulty breathing] begin [for the] current illness? to estimate the onset of the current illness. Pulse was categorized as low, normal, or high based on age‐related heart rate values.[13] Presence of apnea was recorded daily by site investigators.[14]

Nasopharyngeal Aspirate Collection and Virology Testing

As described previously, site teams used a standardized protocol to collect nasopharyngeal aspirates,[11] which were tested for respiratory syncytial virus (RSV) types A and B; rhinovirus (RV); parainfluenza virus types 1, 2, and 3; influenza virus types A and B; 2009 novel H1N1; human metapneumovirus; coronaviruses NL‐63, HKU1, OC43, and 229E; enterovirus, and adenovirus using polymerase chain reaction.[11, 15, 16, 17]

Defining Clinical Improvement and Worsening

Clinical improvement criteria were based on the 2006 AAP guidelines.[9] For respiratory rate and oxygen saturation, clinicians estimated average daily respiratory rate and oxygen saturation based on the recorded readings from the previous 24 hours. This estimation reflects the process clinicians use when rounding on their hospitalized patients, and thus may be more similar to standard clinical practice than a calculated mean. The respiratory rate criteria are adjusted for age.[18, 19] For daily estimated average oxygen saturation we used the AAP criteria of RAO2 saturation of 90%. Considering that oxygen saturation is the main determinant of LOS,[20] healthy infants age <6 months may have transient oxygen saturations of around 80%,[21] and that errors in estimation may occur, we included a lowest RAO2 of 88% in our improvement criteria. By combining the dichotomized estimated oxygen saturation (90% or not) with the lower limit of 88%, there was little room for erroneous conclusions. A child was considered clinically improved on the earliest date he/she met all of the following criteria: (1) none or mild retractions and improved or stable retractions compared with the previous inpatient day; (2) daily estimated average respiratory rate (RR) <60 breaths per minute for age <6 months, <55 breaths/minute for age 6 to 11 months, and <45 breaths/minute for age 12 months with a decreasing or stable trend over the course of the current day; (3) daily estimated average RAO2 saturation 90%, lowest RAO2 saturation 88%[21]; and (4) not receiving intravenous (IV) fluids or for children receiving IV fluids a clinician report of the child maintaining oral hydration. Children who reached the clinical improvement criteria were considered clinically worse if they required intensive care or had the inverse of 1 of the improvement criteria: moderate/severe retractions that were worse compared with the previous inpatient day, daily average RR 60 with an increasing trend over the current day, need for oxygen, or need for IV fluids.

Statistical Analyses

All analyses were performed using Stata 12.0 (StataCorp, College Station, TX). Data are presented as proportions with 95% confidence intervals (95% CIs), means with standard deviations, and medians with interquartile ranges (IQR). To examine potential factors associated with clinical worsening after reaching clinical improvement, we used 2, Fisher exact, Student t test, and Kruskall‐Wallis tests, as appropriate.

Adjusted analyses used generalized linear mixed models with a logit link to identify independent risk factors for worsening after reaching clinical improvement. Fixed effects for patient‐level factors and a random site effect were used. Factors were tested for inclusion in the multivariable model if they were found to be associated with worsening in unadjusted analyses (P<0.20) or were considered clinically important. Results are reported as odds ratios with 95% CIs.

We performed several sensitivity analyses to evaluate these improvement criteria: (1) we excluded the lowest RAO2 saturation requirement of 88%, (2) we examined a 94% daily estimated average RAO2 saturation threshold,[22] (3) we examined a 95% daily estimated average RAO2 saturation threshold,[8] and (4) we examined children age <12 months with no history of wheeze.

RESULTS

There were 1916 children hospitalized with bronchiolitis with data on all factors used to define clinical improvement and clinical worsening. The median number of days from the beginning of difficulty breathing until admission was 2 days (IQR, 15.5 days; range, 18 days) and from the beginning of difficulty breathing until clinical improvement was 4 days (IQR, 37.5 days; range, 133 days) (Figure 1). The variance for days to admission was significantly less than the variance for days to clinical improvement (P<0.001).

Figure 1
Time course of illness for children hospitalized with bronchiolitis.

In this observational study, clinicians discharged 214 (11%) of the 1916 children before meeting the definition of clinical improvement. Thus, 1702 (89%; 95% CI: 87%‐90%) children reached the clinical improvement criteria, had a LOS >1 day, and had data on all factors (Figure 2).

Figure 2
Flow diagram of the study population. *Eight children were worsened on more than 1 criterion. Abbreviations: ICU, intensive care unit; IV, intravenous; LOS, length of stay; RR, respiratory rate.

Of the 1702 children who met the clinical improvement criteria, there were 76 children (4%; 95% CI: 3%5%) who worsened (Figure 2). The worsening occurred within a median of 1 day (IQR, 13 days) of clinical improvement. Forty‐six (3%) of the children required transfer to the ICU (1 required intubation, 1 required continuous positive airway pressure, and 4 had apnea), 23 (1%) required oxygen, and 17 (1%) required IV fluids. Eight percent of children met multiple criteria for worsening. A comparison between children who did and did not worsen is shown in Table 1. In general, children who worsened after improvement were younger and born earlier. These children also presented in more severe respiratory distress, had moderate or severe retractions, oxygen saturation <85% at hospitalization, inadequate oral intake, and apnea documented during the hospitalization. Neither viral etiology nor site of care influenced whether the children worsened after improving. However, stratified analysis of children based on initial location of admission (ie, ICU or ward) showed that among the children admitted to the ICU from the emergency department (ED), 89% met the improvement criteria and 19% clinically worsened. In contrast, among children admitted to the ward from the ED, 89% met the improvement criteria, and only 2% clinically worsened. Stratified multivariable models based on the initial location of admission from the ED (ie, ICU or ward) were not possible due to small sample sizes after stratification. None of these children had relapse events requiring rehospitalization within either 24 hours or 7 days of discharge.

Characteristics of Children Who Did Not Worsen Versus Those Who Worsened After Clinical Improvement
 Did Not Worsen, n=1,626Worsened, n=76P Value
  • NOTE: Abbreviations: ABG, arterial blood gas; ED, emergency department; HRV, human rhinovirus; IQR, interquartile range; RSV, respiratory syncytial virus.

Demographic characteristics   
Age <2 months, %2957<0.001
Month of birth, %  0.02
OctoberMarch6175 
AprilSeptember3925 
Sex, %  0.51
Male5955 
Female4145 
Race, %  0.050
White6358 
Black2334 
Other or missing148 
Hispanic ethnicity, %37220.01
Insurance, %  0.87
Nonprivate6867 
Private3233 
Medical history   
Gestational age <37 weeks, %23390.002
Birth weight, %  0.52
<5 lbs1312 
5 lbs3441 
7 lbs5347 
Mother's age, median (IQR)27 (2333)27 (2233)0.54
Is or was breastfed, %61510.10
Smoked during pregnancy, %15200.22
Exposure to smoke, %13200.11
Family history of asthma, %  0.89
Neither parent6864 
Either mother or father2730 
Both parents44 
Do not know/missing21 
History of wheezing, %23170.24
History of eczema, %1670.04
History of intubation, %9120.50
Major, relevant, comorbid medical disorder, %20240.46
Current illness   
When difficulty breathing began, preadmission, %0.63
1 day7075 
<1 day2823 
No difficulty preadmission23 
Weight, lbs, median (IQR)12.3 (8.817.4)9.0 (6.613.2)0.001
Temperature, F, median (IQR)99.5 (98.6100.6)99.4 (98.1100.4)0.06
Pulse, beats per minute by age  0.82
Low0.30 
Normal4846 
High5154 
Respiratory rate, breaths per minute, median (IQR)48 (4060)48 (3864)0.28
Retractions, %  0.001
None2225 
Mild4324 
Moderate2633 
Severe412 
Missing57 
Oxygen saturation by pulse oximetry or ABG, %0.001
<85412 
8587.934 
8889.950 
9093.91811 
947273 
Oral intake, %  <0.001
Adequate4522 
Inadequate4263 
Missing1314 
Presence of apnea, %724<0.001
RSV‐A, %44410.54
RSV‐B, %30250.36
HRV, %24240.88
Chest x‐ray results during ED/preadmission visit
Atelectasis12130.77
Infiltrate13110.50
Hyperinflated18210.47
Peribronchial cuffing/thickening23170.32
Normal14160.75
White blood count, median (IQR)11.2 (8.714.4)11.9 (9.214.4)0.60
Platelet count, median (IQR)395 (317490)430 (299537)0.56
Sodium, median (IQR)138 (136140)137 (135138)0.19
Hospital length of stay, median (IQR)2 (14)4.5 (28)<0.001
One‐week follow‐up   
Relapse within 24 hours of hospital discharge requiring hospital admission, %0.500.56
Relapse within 7 days of hospital discharge requiring hospital admission, %100.35

On multivariable analysis (Table 2), independent risk factors for worsening after reaching the clinical improvement criteria were young age, preterm birth, and presenting to care with more severe bronchiolitis represented by severe retractions, inadequate oral intake, or apnea. To further evaluate the improvement criteria in the current analysis, multiple sensitivity analyses were conducted. The frequency of clinical worsening after reaching the improvement criteria was stable when we examined different RA02 criteria in sensitivity analyses: (1) excluding RA02 as a criterion for improvement: 90% met improvement criteria and 4% experienced clinical worsening, (2) changing the average RA02 threshold for clinical improvement to 94%: 62% met improvement criteria and 6% experienced clinical worsening, and (3) changing the average RA02 threshold for clinical improvement to 95%: 47% met improvement criteria and 5% experienced clinical worsening. Furthermore, stratifying by age <2 months and restricting to more stringent definitions of bronchiolitis (ie, age <1 year or age <1 year+no history of wheezing) also did not materially change the results (see Supporting Figure 1 in the online version of this article).

Multivariable Model of Factors Associated With a Worsening of Symptoms After Clinical Improvement.
 Odds Ratio95% CIP Value
  • NOTE: Abbreviations: CI, confidence interval.

Age <2 months3.512.07‐5.94<0.001
Gestational age <37 weeks1.941.13‐3.320.02
Retractions   
None1.300.80‐3.230.19
Mild1.0Reference 
Moderate1.910.99‐3.710.06
Severe5.552.1214.50<0.001
Missing1.700.53‐5.420.37
Oral intake   
Adequate1.00Reference 
Inadequate2.541.39‐4.620.002
Unknown/missing1.880.79‐4.440.15
Presence of apnea2.871.45‐5.680.003

We compared the 214 children who were discharged prior to reaching clinical improvement with the 1702 children who reached the clinical improvement criteria. The 214 children were less likely to be age <2 months (22% vs 30%; P=0.02). These 2 groups (214 vs 1702) were similar with respect to severe retractions (2% vs 4%; P=0.13), median respiratory rate (48 vs 48; P=0.42), oxygen saturation <90% (15% vs 11%; P=0.07), inadequate oral intake (50% vs 43%; P=0.13), and rates of relapse events requiring rehospitalization within both 24 hours (0.6% vs 0.6%; P=0.88) and 7 days (1% vs 1%; P=0.90) of discharge.

DISCUSSION

In this large, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that children present to a hospital in a relatively narrow time frame, but their time to recovery in the hospital is highly variable. Nonetheless, 96% of children continued to improve once they had: (1) improving or stable retractions rated as none/mild, (2) a decreasing or stable RR by age, (3) estimated average RAO2 saturation 90% and lowest RAO2 saturation of 88%, and (4) were hydrated. The 4% of children who worsened after clinically improving were more likely to be age <2 months, born <37 weeks, and present with more severe distress (ie, severe retractions, inadequate oral intake, or apnea). Based on the low risk of worsening after clinical improvement, especially among children admitted to the regular ward (2%), we believe these 4 clinical criteria could be used as discharge criteria for this common pediatric illness with a predominantly monophasic clinical course.

Variability in hospital LOS for children with bronchiolitis exists in the United States[3] and internationally.[4, 5] Cheung and colleagues analyzed administrative data from over 75,000 children admitted for bronchiolitis in England between April 2007 and March 2010 and found sixfold variation in LOS between sites. They concluded that this LOS variability was due in part to providers' clinical decision making.[5] Srivastava and colleagues[23] addressed variable clinician decision making in bronchiolitis and 10 other common pediatric conditions by embedding discharge criteria developed by expert consensus into admission order sets. They found that for children with bronchiolitis, the embedded discharge criteria reduced the median LOS from 1.91 to 1.87 days. In contrast to the single‐center data presented by White and colleagues,[24] the prospective, multicenter MARC‐30 data provide a clear understanding of the normal clinical course for children hospitalized with bronchiolitis, determine if children clinically worsen after clinical improvement, and provide data about discharge criteria for children hospitalized with bronchiolitis. Although there is a lack of rigorous published data, the lower tract symptoms of bronchiolitis (eg, cough, retractions) are said to peak on days 5 to 7 of illness and then gradually resolve.[25] In the present study, we found that the time from the onset of difficulty breathing until hospital admission is less variable than the time from the onset of difficulty breathing until either clinical improvement or discharge. Although 75% of children have clinically improved within 7.5 days of difficulty breathing based on the IQR results, the remaining 25% may have a more prolonged recovery in the hospital of up to 3 weeks. Interestingly, prolonged recovery times from bronchiolitis have also been noted in children presenting to the ED[26] and in an outpatient population.[27] It is unclear why 20% to 25% of children at different levels of severity of illness have prolonged recovery from bronchiolitis, but this group of children requires further investigation.

Given the variability of recovery times, clinicians may have difficulty knowing when a child is ready for hospital discharge. One of the main stumbling blocks for discharge readiness in children with bronchiolitis is the interpretation of the oxygen saturation value.[6, 8, 9, 20, 28] However, it should be considered that interpreting the oxygen saturation in a child who is clinically improving in the hospital setting is different than interpreting the oxygen saturation of a child in the ED or the clinic whose clinical course is less certain.[22] In the hospital setting, using the oxygen saturation value in in the AAP guideline,[9] 4% of children clinically worsened after they met the improvement criteria, a clinical pattern observed previously with supplemental oxygen.[28] This unpredictability may explain some of the variation in providers' clinical decision making.[5] The children who worsened, and therefore deserve more cautious discharge planning, were young (<2 months), premature (<37 weeks gestational age), and presented in more severe distress. Those children admitted to the ICU from the ED worsened more commonly than children admitted to the ward (19% vs 2%). Interestingly, the viral etiology of the child's bronchiolitis did not influence whether a child worsened after reaching the improvement criteria. Therefore, although children with RV bronchiolitis have a shorter hospital LOS than children with RSV bronchiolitis,[11] the pattern of recovery did not differ by viral etiology.

In addition to unsafe discharges, clinicians may be concerned about the possibility of readmissions. Although somewhat controversial, hospital readmission is being used as a quality of care metric.[29, 30, 31] One response to minimize readmissions would be for clinicians to observe children for longer than clinically indicated.[32] However, shorter LOS is not necessarily associated with increased readmission rates.[33] Given that the geometric mean of hospital charges per child with bronchiolitis increased from $6380 in 2000 to $8530 in 2009,[34] the potential for safely reducing hospital LOS by using the discharge criteria proposed in the current study instead of other criteria[8] may net substantial cost savings. Furthermore, reducing LOS would decrease the time children expose others to these respiratory viruses and possibly reduce medical errors.[35]

Our study has some potential limitations. Because the study participants were all hospitalized, these data do not inform admission or discharge decisions from either the ED or the clinic; but other data address those clinical scenarios.[22] Also, the 16 sites that participated in this study were large, urban teaching hospitals. Consequently, these results are not necessarily generalizable to smaller community hospitals. Although numerous data points were required to enter the analytic cohort, only 9% of the sample was excluded for missing data. There were 214 children who did not meet our improvement criteria by the time of discharge. Although the inability to include these children in the analysis may be seen as a limitation, this practice variability underscores the need for more data about discharging hospitalized children with bronchiolitis. Last, site teams reviewed medical records daily. More frequent recording of the clinical course would have yielded more granular data, but the current methodology replicates how data are generally presented during patient care rounds, when decisions about suitability for discharge are often considered.

CONCLUSION

We documented in this large multicenter study that most children hospitalized with bronchiolitis had a wide range of time to recovery, but the vast majority continued to improve once they reached the identified clinical criteria that predict a safe discharge to home. The children who worsened after clinical improvement were more likely to be younger, premature infants presenting in more severe distress. Although additional prospective validation of these hospital discharge criteria is warranted, these data may help clinicians make more evidence‐based discharge decisions for a common pediatric illness with high practice variation, both in the United States[3] and in other countries.[4, 5]

Acknowledgements

Collaborators in the MARC‐30 Study: Besh Barcega, MD, Loma Linda University Children's Hospital, Loma Linda, CA; John Cheng, MD, Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Dorothy Damore, MD, New York Presbyterian Hospital‐Cornell, New York, NY; Carlos Delgado, MD, Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Haitham Haddad, MD, Rainbow Babies & Children's Hospital, Cleveland, OH; Paul Hain, MD, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN; Frank LoVecchio, DO, Maricopa Medical Center, Phoenix, AZ; Charles Macias, MD MPH, Texas Children's Hospital, Houston, TX; Jonathan Mansbach, MD, MPH, Boston Children's Hospital, Boston, MA; Eugene Mowad, MD, Akron Children's Hospital, Akron, OH; Brian Pate, MD, Children's Mercy Hospital, Kansas City, MO; Mark Riederer, MD, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN; M. Jason Sanders, MD, Children's Memorial Hermann Hospital, Houston, TX; Alan R. Schroeder, MD, Santa Clara Valley Medical Center, San Jose, CA; Nikhil Shah, MD, New York Presbyterian Hospital‐Cornell, New York, NY; Michelle Stevenson, MD, MS, Kosair Children's Hospital, Louisville, KY; Erin Stucky Fisher, MD, Rady Children's Hospital, San Diego, CA; Stephen Teach, MD, MPH, Children's National Medical Center, Washington, DC; Lisa Zaoutis, MD, Children's Hospital of Philadelphia, Philadelphia, PA.

Disclosures: This study was supported by grants U01 AI‐67693 and K23 AI‐77801 from the National Institutes of Health (Bethesda, MD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Drs. Mansbach and Piedra have provided consultation to Regeneron Pharmaceuticals. Otherwise, no authors report any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations.

Although bronchiolitis is the leading cause of hospitalization for US infants,[1] there is a lack of basic prospective data about the expected inpatient clinical course and ongoing uncertainty about when a hospitalized child is ready for discharge to home.[2] This lack of data about children's readiness for discharge may result in variable hospital length‐of‐stay (LOS).[3, 4, 5]

One specific source of variability in discharge readiness and LOS variability may be the lack of consensus about safe threshold oxygen saturation values for discharge in children hospitalized with bronchiolitis.[6, 7] In 2006, the Scottish Intercollegiate Guidelines Network recommended a discharge room air oxygen (RAO2) saturation threshold of 95%.[8] The same year, the American Academy of Pediatrics (AAP) bronchiolitis clinical practice guideline stated that oxygen is not needed for children with RAO2 saturations 90% who are feeding well and have minimal respiratory distress.[9] There is a need for prospective studies to help clinicians make evidenced‐based discharge decisions for this common condition.

We performed a prospective, multicenter, multiyear study[10, 11, 12] to examine the typical inpatient clinical course of and to develop hospital discharge guidelines for children age <2 years hospitalized with bronchiolitis. We hypothesized that children would not worsen clinically and would be safe to discharge home once their respiratory status improved and they were able to remain hydrated.

METHODS

Study Design and Population

We conducted a prospective, multicenter cohort study for 3 consecutive years during the 2007 to 2010 winter seasons, as part of the Multicenter Airway Research Collaboration (MARC), a program of the Emergency Medicine Network (www.emnet‐usa.org). The number of participating sites varied over the 3 years: 13 in year 1, 16 in year 2, and 14 in year 3. Each month from November 1 until March 31, site investigators across 12 US states used a standardized protocol to enroll a target number of consecutive patients from the inpatient wards and the intensive care unit (ICU). We aimed to enroll 20% of our total sample from the ICU. To over sample children in the ICU, the ward and ICU enrollments were separate. Once the site reached their target enrollment for that month, the investigators would stop enrollment until the beginning of the following month.

All patients were treated at the discretion of the treating physician. Inclusion criteria were an attending physician's diagnosis of bronchiolitis, age <2 years, and the ability of the parent/guardian to give informed consent. The exclusion criteria were previous enrollment and transfer to a participating hospital >48 hours after the original admission time. Therefore, children with comorbid conditions were included in this study. All consent and data forms were translated into Spanish. The institutional review board at each of the 16 participating hospitals approved the study.

Of the 2207 enrolled children, we excluded 109 (5%) children with a hospital LOS <1 day due to inadequate time to capture the required data for the present analysis. Among the 2098 remaining children, 1916 (91%) had daily inpatient data on all factors used to define clinical improvement and clinical worsening. Thus, the analytic cohort was comprised of 1916 children hospitalized for bronchiolitis.

Data Collection

Investigators conducted detailed structured interviews. Chart reviews were conducted to obtain preadmission and daily hospital clinical data including respiratory rates, daily respiratory rate trends, degree of retractions, oxygen saturation, daily oxygen saturation trends, medical management, and disposition. These data were manually reviewed, and site investigators were queried about missing data and discrepancies. A follow‐up telephone interview was conducted with families 1 week after discharge to examine relapse events at both 24 hours and 7 days.

We used the question: How long ago did the following symptoms [eg, difficulty breathing] begin [for the] current illness? to estimate the onset of the current illness. Pulse was categorized as low, normal, or high based on age‐related heart rate values.[13] Presence of apnea was recorded daily by site investigators.[14]

Nasopharyngeal Aspirate Collection and Virology Testing

As described previously, site teams used a standardized protocol to collect nasopharyngeal aspirates,[11] which were tested for respiratory syncytial virus (RSV) types A and B; rhinovirus (RV); parainfluenza virus types 1, 2, and 3; influenza virus types A and B; 2009 novel H1N1; human metapneumovirus; coronaviruses NL‐63, HKU1, OC43, and 229E; enterovirus, and adenovirus using polymerase chain reaction.[11, 15, 16, 17]

Defining Clinical Improvement and Worsening

Clinical improvement criteria were based on the 2006 AAP guidelines.[9] For respiratory rate and oxygen saturation, clinicians estimated average daily respiratory rate and oxygen saturation based on the recorded readings from the previous 24 hours. This estimation reflects the process clinicians use when rounding on their hospitalized patients, and thus may be more similar to standard clinical practice than a calculated mean. The respiratory rate criteria are adjusted for age.[18, 19] For daily estimated average oxygen saturation we used the AAP criteria of RAO2 saturation of 90%. Considering that oxygen saturation is the main determinant of LOS,[20] healthy infants age <6 months may have transient oxygen saturations of around 80%,[21] and that errors in estimation may occur, we included a lowest RAO2 of 88% in our improvement criteria. By combining the dichotomized estimated oxygen saturation (90% or not) with the lower limit of 88%, there was little room for erroneous conclusions. A child was considered clinically improved on the earliest date he/she met all of the following criteria: (1) none or mild retractions and improved or stable retractions compared with the previous inpatient day; (2) daily estimated average respiratory rate (RR) <60 breaths per minute for age <6 months, <55 breaths/minute for age 6 to 11 months, and <45 breaths/minute for age 12 months with a decreasing or stable trend over the course of the current day; (3) daily estimated average RAO2 saturation 90%, lowest RAO2 saturation 88%[21]; and (4) not receiving intravenous (IV) fluids or for children receiving IV fluids a clinician report of the child maintaining oral hydration. Children who reached the clinical improvement criteria were considered clinically worse if they required intensive care or had the inverse of 1 of the improvement criteria: moderate/severe retractions that were worse compared with the previous inpatient day, daily average RR 60 with an increasing trend over the current day, need for oxygen, or need for IV fluids.

Statistical Analyses

All analyses were performed using Stata 12.0 (StataCorp, College Station, TX). Data are presented as proportions with 95% confidence intervals (95% CIs), means with standard deviations, and medians with interquartile ranges (IQR). To examine potential factors associated with clinical worsening after reaching clinical improvement, we used 2, Fisher exact, Student t test, and Kruskall‐Wallis tests, as appropriate.

Adjusted analyses used generalized linear mixed models with a logit link to identify independent risk factors for worsening after reaching clinical improvement. Fixed effects for patient‐level factors and a random site effect were used. Factors were tested for inclusion in the multivariable model if they were found to be associated with worsening in unadjusted analyses (P<0.20) or were considered clinically important. Results are reported as odds ratios with 95% CIs.

We performed several sensitivity analyses to evaluate these improvement criteria: (1) we excluded the lowest RAO2 saturation requirement of 88%, (2) we examined a 94% daily estimated average RAO2 saturation threshold,[22] (3) we examined a 95% daily estimated average RAO2 saturation threshold,[8] and (4) we examined children age <12 months with no history of wheeze.

RESULTS

There were 1916 children hospitalized with bronchiolitis with data on all factors used to define clinical improvement and clinical worsening. The median number of days from the beginning of difficulty breathing until admission was 2 days (IQR, 15.5 days; range, 18 days) and from the beginning of difficulty breathing until clinical improvement was 4 days (IQR, 37.5 days; range, 133 days) (Figure 1). The variance for days to admission was significantly less than the variance for days to clinical improvement (P<0.001).

Figure 1
Time course of illness for children hospitalized with bronchiolitis.

In this observational study, clinicians discharged 214 (11%) of the 1916 children before meeting the definition of clinical improvement. Thus, 1702 (89%; 95% CI: 87%‐90%) children reached the clinical improvement criteria, had a LOS >1 day, and had data on all factors (Figure 2).

Figure 2
Flow diagram of the study population. *Eight children were worsened on more than 1 criterion. Abbreviations: ICU, intensive care unit; IV, intravenous; LOS, length of stay; RR, respiratory rate.

Of the 1702 children who met the clinical improvement criteria, there were 76 children (4%; 95% CI: 3%5%) who worsened (Figure 2). The worsening occurred within a median of 1 day (IQR, 13 days) of clinical improvement. Forty‐six (3%) of the children required transfer to the ICU (1 required intubation, 1 required continuous positive airway pressure, and 4 had apnea), 23 (1%) required oxygen, and 17 (1%) required IV fluids. Eight percent of children met multiple criteria for worsening. A comparison between children who did and did not worsen is shown in Table 1. In general, children who worsened after improvement were younger and born earlier. These children also presented in more severe respiratory distress, had moderate or severe retractions, oxygen saturation <85% at hospitalization, inadequate oral intake, and apnea documented during the hospitalization. Neither viral etiology nor site of care influenced whether the children worsened after improving. However, stratified analysis of children based on initial location of admission (ie, ICU or ward) showed that among the children admitted to the ICU from the emergency department (ED), 89% met the improvement criteria and 19% clinically worsened. In contrast, among children admitted to the ward from the ED, 89% met the improvement criteria, and only 2% clinically worsened. Stratified multivariable models based on the initial location of admission from the ED (ie, ICU or ward) were not possible due to small sample sizes after stratification. None of these children had relapse events requiring rehospitalization within either 24 hours or 7 days of discharge.

Characteristics of Children Who Did Not Worsen Versus Those Who Worsened After Clinical Improvement
 Did Not Worsen, n=1,626Worsened, n=76P Value
  • NOTE: Abbreviations: ABG, arterial blood gas; ED, emergency department; HRV, human rhinovirus; IQR, interquartile range; RSV, respiratory syncytial virus.

Demographic characteristics   
Age <2 months, %2957<0.001
Month of birth, %  0.02
OctoberMarch6175 
AprilSeptember3925 
Sex, %  0.51
Male5955 
Female4145 
Race, %  0.050
White6358 
Black2334 
Other or missing148 
Hispanic ethnicity, %37220.01
Insurance, %  0.87
Nonprivate6867 
Private3233 
Medical history   
Gestational age <37 weeks, %23390.002
Birth weight, %  0.52
<5 lbs1312 
5 lbs3441 
7 lbs5347 
Mother's age, median (IQR)27 (2333)27 (2233)0.54
Is or was breastfed, %61510.10
Smoked during pregnancy, %15200.22
Exposure to smoke, %13200.11
Family history of asthma, %  0.89
Neither parent6864 
Either mother or father2730 
Both parents44 
Do not know/missing21 
History of wheezing, %23170.24
History of eczema, %1670.04
History of intubation, %9120.50
Major, relevant, comorbid medical disorder, %20240.46
Current illness   
When difficulty breathing began, preadmission, %0.63
1 day7075 
<1 day2823 
No difficulty preadmission23 
Weight, lbs, median (IQR)12.3 (8.817.4)9.0 (6.613.2)0.001
Temperature, F, median (IQR)99.5 (98.6100.6)99.4 (98.1100.4)0.06
Pulse, beats per minute by age  0.82
Low0.30 
Normal4846 
High5154 
Respiratory rate, breaths per minute, median (IQR)48 (4060)48 (3864)0.28
Retractions, %  0.001
None2225 
Mild4324 
Moderate2633 
Severe412 
Missing57 
Oxygen saturation by pulse oximetry or ABG, %0.001
<85412 
8587.934 
8889.950 
9093.91811 
947273 
Oral intake, %  <0.001
Adequate4522 
Inadequate4263 
Missing1314 
Presence of apnea, %724<0.001
RSV‐A, %44410.54
RSV‐B, %30250.36
HRV, %24240.88
Chest x‐ray results during ED/preadmission visit
Atelectasis12130.77
Infiltrate13110.50
Hyperinflated18210.47
Peribronchial cuffing/thickening23170.32
Normal14160.75
White blood count, median (IQR)11.2 (8.714.4)11.9 (9.214.4)0.60
Platelet count, median (IQR)395 (317490)430 (299537)0.56
Sodium, median (IQR)138 (136140)137 (135138)0.19
Hospital length of stay, median (IQR)2 (14)4.5 (28)<0.001
One‐week follow‐up   
Relapse within 24 hours of hospital discharge requiring hospital admission, %0.500.56
Relapse within 7 days of hospital discharge requiring hospital admission, %100.35

On multivariable analysis (Table 2), independent risk factors for worsening after reaching the clinical improvement criteria were young age, preterm birth, and presenting to care with more severe bronchiolitis represented by severe retractions, inadequate oral intake, or apnea. To further evaluate the improvement criteria in the current analysis, multiple sensitivity analyses were conducted. The frequency of clinical worsening after reaching the improvement criteria was stable when we examined different RA02 criteria in sensitivity analyses: (1) excluding RA02 as a criterion for improvement: 90% met improvement criteria and 4% experienced clinical worsening, (2) changing the average RA02 threshold for clinical improvement to 94%: 62% met improvement criteria and 6% experienced clinical worsening, and (3) changing the average RA02 threshold for clinical improvement to 95%: 47% met improvement criteria and 5% experienced clinical worsening. Furthermore, stratifying by age <2 months and restricting to more stringent definitions of bronchiolitis (ie, age <1 year or age <1 year+no history of wheezing) also did not materially change the results (see Supporting Figure 1 in the online version of this article).

Multivariable Model of Factors Associated With a Worsening of Symptoms After Clinical Improvement.
 Odds Ratio95% CIP Value
  • NOTE: Abbreviations: CI, confidence interval.

Age <2 months3.512.07‐5.94<0.001
Gestational age <37 weeks1.941.13‐3.320.02
Retractions   
None1.300.80‐3.230.19
Mild1.0Reference 
Moderate1.910.99‐3.710.06
Severe5.552.1214.50<0.001
Missing1.700.53‐5.420.37
Oral intake   
Adequate1.00Reference 
Inadequate2.541.39‐4.620.002
Unknown/missing1.880.79‐4.440.15
Presence of apnea2.871.45‐5.680.003

We compared the 214 children who were discharged prior to reaching clinical improvement with the 1702 children who reached the clinical improvement criteria. The 214 children were less likely to be age <2 months (22% vs 30%; P=0.02). These 2 groups (214 vs 1702) were similar with respect to severe retractions (2% vs 4%; P=0.13), median respiratory rate (48 vs 48; P=0.42), oxygen saturation <90% (15% vs 11%; P=0.07), inadequate oral intake (50% vs 43%; P=0.13), and rates of relapse events requiring rehospitalization within both 24 hours (0.6% vs 0.6%; P=0.88) and 7 days (1% vs 1%; P=0.90) of discharge.

DISCUSSION

In this large, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that children present to a hospital in a relatively narrow time frame, but their time to recovery in the hospital is highly variable. Nonetheless, 96% of children continued to improve once they had: (1) improving or stable retractions rated as none/mild, (2) a decreasing or stable RR by age, (3) estimated average RAO2 saturation 90% and lowest RAO2 saturation of 88%, and (4) were hydrated. The 4% of children who worsened after clinically improving were more likely to be age <2 months, born <37 weeks, and present with more severe distress (ie, severe retractions, inadequate oral intake, or apnea). Based on the low risk of worsening after clinical improvement, especially among children admitted to the regular ward (2%), we believe these 4 clinical criteria could be used as discharge criteria for this common pediatric illness with a predominantly monophasic clinical course.

Variability in hospital LOS for children with bronchiolitis exists in the United States[3] and internationally.[4, 5] Cheung and colleagues analyzed administrative data from over 75,000 children admitted for bronchiolitis in England between April 2007 and March 2010 and found sixfold variation in LOS between sites. They concluded that this LOS variability was due in part to providers' clinical decision making.[5] Srivastava and colleagues[23] addressed variable clinician decision making in bronchiolitis and 10 other common pediatric conditions by embedding discharge criteria developed by expert consensus into admission order sets. They found that for children with bronchiolitis, the embedded discharge criteria reduced the median LOS from 1.91 to 1.87 days. In contrast to the single‐center data presented by White and colleagues,[24] the prospective, multicenter MARC‐30 data provide a clear understanding of the normal clinical course for children hospitalized with bronchiolitis, determine if children clinically worsen after clinical improvement, and provide data about discharge criteria for children hospitalized with bronchiolitis. Although there is a lack of rigorous published data, the lower tract symptoms of bronchiolitis (eg, cough, retractions) are said to peak on days 5 to 7 of illness and then gradually resolve.[25] In the present study, we found that the time from the onset of difficulty breathing until hospital admission is less variable than the time from the onset of difficulty breathing until either clinical improvement or discharge. Although 75% of children have clinically improved within 7.5 days of difficulty breathing based on the IQR results, the remaining 25% may have a more prolonged recovery in the hospital of up to 3 weeks. Interestingly, prolonged recovery times from bronchiolitis have also been noted in children presenting to the ED[26] and in an outpatient population.[27] It is unclear why 20% to 25% of children at different levels of severity of illness have prolonged recovery from bronchiolitis, but this group of children requires further investigation.

Given the variability of recovery times, clinicians may have difficulty knowing when a child is ready for hospital discharge. One of the main stumbling blocks for discharge readiness in children with bronchiolitis is the interpretation of the oxygen saturation value.[6, 8, 9, 20, 28] However, it should be considered that interpreting the oxygen saturation in a child who is clinically improving in the hospital setting is different than interpreting the oxygen saturation of a child in the ED or the clinic whose clinical course is less certain.[22] In the hospital setting, using the oxygen saturation value in in the AAP guideline,[9] 4% of children clinically worsened after they met the improvement criteria, a clinical pattern observed previously with supplemental oxygen.[28] This unpredictability may explain some of the variation in providers' clinical decision making.[5] The children who worsened, and therefore deserve more cautious discharge planning, were young (<2 months), premature (<37 weeks gestational age), and presented in more severe distress. Those children admitted to the ICU from the ED worsened more commonly than children admitted to the ward (19% vs 2%). Interestingly, the viral etiology of the child's bronchiolitis did not influence whether a child worsened after reaching the improvement criteria. Therefore, although children with RV bronchiolitis have a shorter hospital LOS than children with RSV bronchiolitis,[11] the pattern of recovery did not differ by viral etiology.

In addition to unsafe discharges, clinicians may be concerned about the possibility of readmissions. Although somewhat controversial, hospital readmission is being used as a quality of care metric.[29, 30, 31] One response to minimize readmissions would be for clinicians to observe children for longer than clinically indicated.[32] However, shorter LOS is not necessarily associated with increased readmission rates.[33] Given that the geometric mean of hospital charges per child with bronchiolitis increased from $6380 in 2000 to $8530 in 2009,[34] the potential for safely reducing hospital LOS by using the discharge criteria proposed in the current study instead of other criteria[8] may net substantial cost savings. Furthermore, reducing LOS would decrease the time children expose others to these respiratory viruses and possibly reduce medical errors.[35]

Our study has some potential limitations. Because the study participants were all hospitalized, these data do not inform admission or discharge decisions from either the ED or the clinic; but other data address those clinical scenarios.[22] Also, the 16 sites that participated in this study were large, urban teaching hospitals. Consequently, these results are not necessarily generalizable to smaller community hospitals. Although numerous data points were required to enter the analytic cohort, only 9% of the sample was excluded for missing data. There were 214 children who did not meet our improvement criteria by the time of discharge. Although the inability to include these children in the analysis may be seen as a limitation, this practice variability underscores the need for more data about discharging hospitalized children with bronchiolitis. Last, site teams reviewed medical records daily. More frequent recording of the clinical course would have yielded more granular data, but the current methodology replicates how data are generally presented during patient care rounds, when decisions about suitability for discharge are often considered.

CONCLUSION

We documented in this large multicenter study that most children hospitalized with bronchiolitis had a wide range of time to recovery, but the vast majority continued to improve once they reached the identified clinical criteria that predict a safe discharge to home. The children who worsened after clinical improvement were more likely to be younger, premature infants presenting in more severe distress. Although additional prospective validation of these hospital discharge criteria is warranted, these data may help clinicians make more evidence‐based discharge decisions for a common pediatric illness with high practice variation, both in the United States[3] and in other countries.[4, 5]

Acknowledgements

Collaborators in the MARC‐30 Study: Besh Barcega, MD, Loma Linda University Children's Hospital, Loma Linda, CA; John Cheng, MD, Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Dorothy Damore, MD, New York Presbyterian Hospital‐Cornell, New York, NY; Carlos Delgado, MD, Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Haitham Haddad, MD, Rainbow Babies & Children's Hospital, Cleveland, OH; Paul Hain, MD, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN; Frank LoVecchio, DO, Maricopa Medical Center, Phoenix, AZ; Charles Macias, MD MPH, Texas Children's Hospital, Houston, TX; Jonathan Mansbach, MD, MPH, Boston Children's Hospital, Boston, MA; Eugene Mowad, MD, Akron Children's Hospital, Akron, OH; Brian Pate, MD, Children's Mercy Hospital, Kansas City, MO; Mark Riederer, MD, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN; M. Jason Sanders, MD, Children's Memorial Hermann Hospital, Houston, TX; Alan R. Schroeder, MD, Santa Clara Valley Medical Center, San Jose, CA; Nikhil Shah, MD, New York Presbyterian Hospital‐Cornell, New York, NY; Michelle Stevenson, MD, MS, Kosair Children's Hospital, Louisville, KY; Erin Stucky Fisher, MD, Rady Children's Hospital, San Diego, CA; Stephen Teach, MD, MPH, Children's National Medical Center, Washington, DC; Lisa Zaoutis, MD, Children's Hospital of Philadelphia, Philadelphia, PA.

Disclosures: This study was supported by grants U01 AI‐67693 and K23 AI‐77801 from the National Institutes of Health (Bethesda, MD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Drs. Mansbach and Piedra have provided consultation to Regeneron Pharmaceuticals. Otherwise, no authors report any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations.

References
  1. Yorita KL, Holman RC, Sejvar JJ, Steiner CA, Schonberger LB. Infectious disease hospitalizations among infants in the United States. Pediatrics. 2008;121(2):244252.
  2. Cunningham S. “A hospital is no place to be sick” Samuel Goldwyn (1882–1974). Arch Dis Child. 2009;94(8):565566.
  3. Christakis D.A, Cowan C.A, Garrison MM, Molteni R, Marcuse E, Zerr DM. Variation in inpatient diagnostic testing and management of bronchiolitis. Pediatrics. 2005;115(4):878884.
  4. Behrendt CE, Decker MD, Burch DJ, Watson PH International variation in the management of infants hospitalized with respiratory syncytial virus. International RSV Study Group. Eur J Pediatr. 1998;157(3):215220.
  5. Cheung CR, Smith H, Thurland K, Duncan H, Semple MG. Population variation in admission rates and duration of inpatient stay for bronchiolitis in England. Arch Dis Child. 2013;98(1):5759.
  6. Schroeder AR, Marmor AK, Pantell RH, Newman TB. Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations. Arch Pediatr Adolesc Med. 2004;158(6):527530.
  7. Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics. 2011;128(4):740752.
  8. Scottish Intercollegiate Guidelines Network. Bronchiolitis in children (SIGN 91). In: NHS Quality Improvement Scotland. Edinburgh, Scotland: Scottish Intercollegiate Guidelines Network; 2006.
  9. Lieberthal AS, Bauchner H, Hall CB, et al. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118(4):17741793.
  10. Mansbach JM, Piedra PA, Stevenson MD, et al. Prospective multicenter study of children with bronchiolitis requiring mechanical ventilation. Pediatrics. 2012;130(3):e492e500.
  11. Mansbach JM, Piedra PA, Teach SJ, et al. Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med. 2012;166(8):700706.
  12. Schroeder AR, Mansbach JM, Stevenson M, et al. Apnea in children hospitalized with bronchiolitis. Pediatrics. 2013;132(5):e1194e1201.
  13. Bernstein D. Evaluation of the cardiovascular system: history and physical evaluation. In: Kliegman RM, Stanton BF, St. Geme JW III, Schor NF, Behrman RF, eds. Nelson Textbook of Pediatrics. Philadelphia, PA: Elsevier Saunders; 2011:15291536.
  14. Schroeder AR, Mansbach JM, Stevenson M, et al. Apnea in children hospitalized with bronchiolitis. Pediatrics. 2013;132(5):e1194e1201.
  15. Beckham JD, Cadena A, Lin J, et al. Respiratory viral infections in patients with chronic, obstructive pulmonary disease. J Infect. 2005;50(4):322330.
  16. Knorr L, Fox JD, Tilley PA, Ahmed‐Bentley J. Evaluation of real‐time PCR for diagnosis of Bordetella pertussis infection. BMC Infect Dis. 2006;6:62.
  17. Winchell JM, Thurman KA, Mitchell SL, Thacker WL, Fields BS. Evaluation of three real‐time PCR assays for detection of Mycoplasma pneumoniae in an outbreak investigation. J Clin Microbiol. 2008;46(9):31163118.
  18. Fleming S., Thompson M, Stevens R, et al. Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. Lancet. 2011;377(9770):10111018.
  19. Bonafide CP, Brady PW, Keren R, Conway PH, Marsolo K, Daymont C. Development of heart and respiratory rate percentile curves for hospitalized children. Pediatrics. 2013;131(4):e1150e1157.
  20. Unger S, Cunningham S. Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis. Pediatrics. 2008;121(3):470475.
  21. Hunt CE, Corwin MJ, Lister G, et al. Longitudinal assessment of hemoglobin oxygen saturation in healthy infants during the first 6 months of age. Collaborative Home Infant Monitoring Evaluation (CHIME) Study Group. J Pediatr. 1999;135(5):580586.
  22. Mansbach JM, Clark S, Christopher NC, et al. Prospective multicenter study of bronchiolitis: predicting safe discharges from the emergency department. Pediatrics. 2008;121(4):680688.
  23. Srivastava R, Stone BL, Patel R, et al. Delays in discharge in a tertiary care pediatric hospital. J Hosp Med. 2009;4(8):481485.
  24. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428436.
  25. Piedra P, Stark A. Bronchiolitis in infants and children: treatment; outcome; and prevention. In: Torchia M, ed. UpToDate. Alphen aan den Rijn, the Netherlands; Wolters Kluwer Health; 2013.
  26. Petruzella FD, Gorelick MH. Duration of illness in infants with bronchiolitis evaluated in the emergency department. Pediatrics. 2010;126(2):285290.
  27. Swingler GH, Hussey GD, Zwarenstein M. Duration of illness in ambulatory children diagnosed with bronchiolitis. Arch Pediatr Adolesc Med. 2000;154(10):9971000.
  28. Cheney J, Barber S, Altamirano L, et al. A clinical pathway for bronchiolitis is effective in reducing readmission rates. J Pediatr. 2005;147(5):622626.
  29. Bardach NS, Vittinghoff E, Asteria‐Penaloza R, et al. Measuring hospital quality using pediatric readmission and revisit rates. Pediatrics. 2013;132(3):429436.
  30. Berry JG, Toomey SL, Zaslavsky AM, et al. Pediatric readmission prevalence and variability across hospitals. JAMA. 2013;309(4):372380.
  31. Hain PD, Gay JC, Berutti TW, Whitney GM, Wang W, Saville BR. Preventability of early readmissions at a children's hospital. Pediatrics. 2013;131(1):e171e181.
  32. Alverson BK, O'Callaghan J. Hospital readmission: quality indicator or statistical inevitability? Pediatrics. 2013;132(3):569570.
  33. Morse RB, Hall M, Fieldston ES, et al. Children's hospitals with shorter lengths of stay do not have higher readmission rates. J Pediatr. 2013;163(4):10341038.e1.
  34. Hasegawa K, Tsugawa Y, Brown DF, Mansbach JM, Camargo CA. Trends in bronchiolitis hospitalizations in the United States, 2000–2009. Pediatrics. 2013;132(1):2836.
  35. McBride SC, Chiang VW, Goldmann DA, Landrigan CP. Preventable adverse events in infants hospitalized with bronchiolitis. Pediatrics. 2005;116(3):603608.
References
  1. Yorita KL, Holman RC, Sejvar JJ, Steiner CA, Schonberger LB. Infectious disease hospitalizations among infants in the United States. Pediatrics. 2008;121(2):244252.
  2. Cunningham S. “A hospital is no place to be sick” Samuel Goldwyn (1882–1974). Arch Dis Child. 2009;94(8):565566.
  3. Christakis D.A, Cowan C.A, Garrison MM, Molteni R, Marcuse E, Zerr DM. Variation in inpatient diagnostic testing and management of bronchiolitis. Pediatrics. 2005;115(4):878884.
  4. Behrendt CE, Decker MD, Burch DJ, Watson PH International variation in the management of infants hospitalized with respiratory syncytial virus. International RSV Study Group. Eur J Pediatr. 1998;157(3):215220.
  5. Cheung CR, Smith H, Thurland K, Duncan H, Semple MG. Population variation in admission rates and duration of inpatient stay for bronchiolitis in England. Arch Dis Child. 2013;98(1):5759.
  6. Schroeder AR, Marmor AK, Pantell RH, Newman TB. Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations. Arch Pediatr Adolesc Med. 2004;158(6):527530.
  7. Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics. 2011;128(4):740752.
  8. Scottish Intercollegiate Guidelines Network. Bronchiolitis in children (SIGN 91). In: NHS Quality Improvement Scotland. Edinburgh, Scotland: Scottish Intercollegiate Guidelines Network; 2006.
  9. Lieberthal AS, Bauchner H, Hall CB, et al. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118(4):17741793.
  10. Mansbach JM, Piedra PA, Stevenson MD, et al. Prospective multicenter study of children with bronchiolitis requiring mechanical ventilation. Pediatrics. 2012;130(3):e492e500.
  11. Mansbach JM, Piedra PA, Teach SJ, et al. Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med. 2012;166(8):700706.
  12. Schroeder AR, Mansbach JM, Stevenson M, et al. Apnea in children hospitalized with bronchiolitis. Pediatrics. 2013;132(5):e1194e1201.
  13. Bernstein D. Evaluation of the cardiovascular system: history and physical evaluation. In: Kliegman RM, Stanton BF, St. Geme JW III, Schor NF, Behrman RF, eds. Nelson Textbook of Pediatrics. Philadelphia, PA: Elsevier Saunders; 2011:15291536.
  14. Schroeder AR, Mansbach JM, Stevenson M, et al. Apnea in children hospitalized with bronchiolitis. Pediatrics. 2013;132(5):e1194e1201.
  15. Beckham JD, Cadena A, Lin J, et al. Respiratory viral infections in patients with chronic, obstructive pulmonary disease. J Infect. 2005;50(4):322330.
  16. Knorr L, Fox JD, Tilley PA, Ahmed‐Bentley J. Evaluation of real‐time PCR for diagnosis of Bordetella pertussis infection. BMC Infect Dis. 2006;6:62.
  17. Winchell JM, Thurman KA, Mitchell SL, Thacker WL, Fields BS. Evaluation of three real‐time PCR assays for detection of Mycoplasma pneumoniae in an outbreak investigation. J Clin Microbiol. 2008;46(9):31163118.
  18. Fleming S., Thompson M, Stevens R, et al. Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. Lancet. 2011;377(9770):10111018.
  19. Bonafide CP, Brady PW, Keren R, Conway PH, Marsolo K, Daymont C. Development of heart and respiratory rate percentile curves for hospitalized children. Pediatrics. 2013;131(4):e1150e1157.
  20. Unger S, Cunningham S. Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis. Pediatrics. 2008;121(3):470475.
  21. Hunt CE, Corwin MJ, Lister G, et al. Longitudinal assessment of hemoglobin oxygen saturation in healthy infants during the first 6 months of age. Collaborative Home Infant Monitoring Evaluation (CHIME) Study Group. J Pediatr. 1999;135(5):580586.
  22. Mansbach JM, Clark S, Christopher NC, et al. Prospective multicenter study of bronchiolitis: predicting safe discharges from the emergency department. Pediatrics. 2008;121(4):680688.
  23. Srivastava R, Stone BL, Patel R, et al. Delays in discharge in a tertiary care pediatric hospital. J Hosp Med. 2009;4(8):481485.
  24. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428436.
  25. Piedra P, Stark A. Bronchiolitis in infants and children: treatment; outcome; and prevention. In: Torchia M, ed. UpToDate. Alphen aan den Rijn, the Netherlands; Wolters Kluwer Health; 2013.
  26. Petruzella FD, Gorelick MH. Duration of illness in infants with bronchiolitis evaluated in the emergency department. Pediatrics. 2010;126(2):285290.
  27. Swingler GH, Hussey GD, Zwarenstein M. Duration of illness in ambulatory children diagnosed with bronchiolitis. Arch Pediatr Adolesc Med. 2000;154(10):9971000.
  28. Cheney J, Barber S, Altamirano L, et al. A clinical pathway for bronchiolitis is effective in reducing readmission rates. J Pediatr. 2005;147(5):622626.
  29. Bardach NS, Vittinghoff E, Asteria‐Penaloza R, et al. Measuring hospital quality using pediatric readmission and revisit rates. Pediatrics. 2013;132(3):429436.
  30. Berry JG, Toomey SL, Zaslavsky AM, et al. Pediatric readmission prevalence and variability across hospitals. JAMA. 2013;309(4):372380.
  31. Hain PD, Gay JC, Berutti TW, Whitney GM, Wang W, Saville BR. Preventability of early readmissions at a children's hospital. Pediatrics. 2013;131(1):e171e181.
  32. Alverson BK, O'Callaghan J. Hospital readmission: quality indicator or statistical inevitability? Pediatrics. 2013;132(3):569570.
  33. Morse RB, Hall M, Fieldston ES, et al. Children's hospitals with shorter lengths of stay do not have higher readmission rates. J Pediatr. 2013;163(4):10341038.e1.
  34. Hasegawa K, Tsugawa Y, Brown DF, Mansbach JM, Camargo CA. Trends in bronchiolitis hospitalizations in the United States, 2000–2009. Pediatrics. 2013;132(1):2836.
  35. McBride SC, Chiang VW, Goldmann DA, Landrigan CP. Preventable adverse events in infants hospitalized with bronchiolitis. Pediatrics. 2005;116(3):603608.
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Address for correspondence and reprint requests: Jonathan M. Mansbach, MD, Boston Children's Hospital, Main Clinical Building, 9 South, #9157, Boston, MA 02115; Telephone: 617‐355‐3191; Fax: 617‐730‐0884; E‐mail: jonathan.mansbach@childrens.harvard.edu
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Pediatric in the Literature

Hospital “Report Cards”: Variation in the Management of Bronchiolitis

Christakis DA, Cowan CA, Garrison MM, Molteni R, Marcuse E, Zerr DM. Variation in Inpatient Diagnostic Testing and Management of Bronchiolitis. Pediatrics. 2005;115:878-4.

Bronchiolitis remains 1 of the most common causes of hospitalization in children within the first 2 years of life. In this analysis, the authors conducted a large retrospective descriptive study of infants who were admitted with bronchiolitis to children’s hospitals across the United States. The study examined the variability in length of stay (LOS), diagnostic testing, medications used, and readmission rates. The authors reviewed data on a total of 17,397 infants younger than 1 year of age. Information was obtained from the Pediatric Health Information System, which includes demographic and diagnostic data on 36 freestanding, noncompeting children’s hospitals. The authors found significant and wide variation in LOS, readmission rates, treatment approaches, and use of diagnostic tests for inpatient management of bronchiolitis.

Results indicated that 72% of patients received chest radiographs, 45% received antibiotics, and 25% received systemic steroids. The mean LOS varied considerably across hospitals, with a range of 2.40–3.90 days. The use of antibiotics varied from 28% to 62%, and the use of chest radiographs varied from 38% to 89%. There was also significant difference in readmission rates, which varied from 0% to 2.7%. The variation between hospitals remained a significant contributor even after controlling for multiple potential confounding factors.

Decreasing LOS and unnecessary medication and test utilization is supportive of pediatric patient safety initiatives. The authors suggest that chest radiographs may be leading to unnecessary use of antibiotics due to presumptive treatment based on nonspecific findings. In addition, the authors hypothesize that increased virologic testing may be cost-effective if it leads to decreased use of antibiotics.

The study concludes that there are considerable, unexplained variations that exist in the inpatient management of bronchiolitis. Development of national guidelines and controlled trials of new therapies and different approaches are indicated. Hospitals need to direct resources at analyzing and improving their inpatient care by implementing a more evidence-based approach to management of this common problem.

Maternal Group B Streptococcal Positivity: Risk factor or not?

Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. 2005;115:1240-6.

Despite implementation of intrapartum antibiotic prophylaxis (IAP) based on maternal screening for group B streptococcus (GBS) colonization, cases of early-onset neonatal GBS disease (EOGBS) continue to occur with significant morbidity and mortality. Researchers at the Brigham and Woman’s Hospital in Boston, MA devised this retrospective analysis to determine which attributes of maternal screening, provision of IAP, or evaluation of newborns for sepsis might influence the persistence of EOGBS cases. A retrospective review of all cases of culture proven EOGBS between 1997 and 2003 identified 25 cases of EOGBS among the 67,260 live births, for an overall incidence of 0.37 per 1000 live births. The incidence in infants of very low birth weight was 3.3 cases per 1,000 live births. Among the mothers of term infants with EOGBS, 14 of 17 (82%) had been screened GBS negative; 1 was GBS unknown. Eight of these 14 GBS negative mothers had at least 1 intrapartum risk factor for neonatal sepsis but did not receive IAP. The authors hypothesize that the negative GBS status in these cases may have provided a false sense of reassurance to obstetricians.

Ten of the 17 term infants were evaluated for sepsis due to clinical signs of illness, while the remaining infants were evaluated based on intrapartum risk factors alone. Interestingly, the retrospective analysis demonstrated that 5 of the 25 bacterial isolates were resistant to clindamycin and/or erythromycin, with another 5 isolates partially resistant to 1 or both of these medications. One case of EOGBS disease was found in the child of a penicillin-allergic mother who received clindamycin for IAP. This article highlights the importance of reviewing intrapartum risk factors other than GBS colonization—i.e., delivery at <37 weeks’ gestation,

 

 

intrapartum temperature >100.4°C, or signs of clinical chorioamnionitis, in addition to documenting if IAP was provided and with which antibiotic in evaluation of neonates for possible EOGBS.

Treating Refractory Kawasaki Syndrome with Infliximab

Burns JC, Mason, WH, Hauger SB, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005;146: 662-7.

Citing a 10% to 20% failure rate for intravenous immunoglobulin (IVIG) in combination with high-dose aspirin (ASA) for treating Kawasaki syndrome (KS), these authors present a case series of patients with refractory KS who were treated with infliximab. Several treatments have been suggested for KS patients with persistent or recrudescent fever after IVIG and ASA; however, no clinical trials have established an optimal treatment. Tumor necrosis factor-alpha (TNF-α) has been shown not only to be elevated in patients with KS but also to correlate with development of coronary artery aneurysms. Infliximab, a TNF-α antagonist licensed for clinical use (Remicade, Centocor, Malvern, PA), is used in several immunologic diseases with inflammation mediated by this proinflammatory cytokine. In this poorly controlled case series, 17 patients with acute KS received infliximab after at least 2 doses of IVIG (2 g/kg) and daily ASA (80–100 mg/kg/day) because they were either persistently febrile (16 patients) or had severe arthritis without fever (1 patient). Fourteen of 16 febrile patients became afebrile. C-reactive protein was lower after infliximab in all patients with elevated CRP when remeasured within 48 hours of treatment. In addition to these signs of inflammation, the researchers also studied patient outcomes.

Of 12 patients with coronary artery abnormalities before treatment with infliximab, 4 had dilatation that resolved after treatment. The remaining 8 had either aneurysms or ectasia that were unchanged after therapy. No patients in the series had complications attributed to infliximab. The authors note that the cost of treatment with infliximab compares favorably with a 2 g/kg dose of IVIG. Appropriately, they also specifically address the potential adverse effects of infliximab, for which the pharmacodynamics, pharmacokinetics and safety have not been established in children <5 years of age. Data with regard to possible complications is inadequate and comes from studies of children and adults who typically receive multiple doses of infliximab for chronic inflammatory conditions that inherently can produce multiorgan symptoms. Of note, infliximab does not carry the risk of possible infectious contamination that treatment with IVIG poses. There are several important limitations to the study that are adequately addressed by the authors. Nonetheless, the series highlights the significance of current and future randomized, controlled clinical trials defining the role of TNF-α antagonism in the treatment of KS.

Do Freestanding Children’s Hospitals Improve Care?

Merenstein D, Egleston B, Diener-West M. Lengths of stay and costs associated with children’s hospitals. Pediatrics. 2005;115: 839-44.

Adult literature has shown that access to more subspecialty oriented care results in higher costs and more procedures but does not guarantee improved outcomes. Researchers from Johns Hopkins School of Medicine and Johns Hopkins School of Public Health hypothesized that freestanding children’s hospitals would have longer lengths of stay (LOS) and higher costs compared with other hospitals with regard to similar diagnoses. To test the hypothesis, they studied 24,322 inpatient encounters for pneumonia, gastroenteritis, respiratory syncytial virus, dehydration, or asthma from the Heathcare Cost and Utilization Project Kids’ Inpatient database 2000. Of these encounters, 3,408 were from 23 different freestanding children’s hospitals, and the remaining 20,194 encounters were from 1,749 non-children’s hospitals. The children’s hospitals were all urban teaching hospitals. After adjusting for potentially confounding variables, the researchers found no significant difference in the LOS by hospital type. In this study, the median cost for an admission at a freestanding hospital was $1,294 more per hospitalization after adjustment for LOS and other potential confounder variables. In addition, the results showed that children’s hospitals were more likely to care for minority patients, patients with Medicaid, patients with multiple diagnoses, and patients transferred from other hospitals. The study design did not include direct measures of quality of care, so it is unclear if the increased cost of admission to a children’s hospital leads to improved care.

 

 

Asthma and Invasive Pneumococcal Infections

Talbot RT, Hartert TV Mitchel E, et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med. 2005; 352: 2082-90.

Current guidelines for pneumococcal vaccination exclude people with asthma, nor do the most recently published guidelines for management of asthma include pneumococcal vaccination. The authors of this study utilized public health databases to perform a nested case-controlled cohort study to determine the risk of pneumococcal disease among people with asthma. By combining a database of active surveillance for invasive pneumococcal disease (IPD) with a state-based managed healthcare program, researchers identified 635 cases of IPD in people with asthma and paired them with 6,350 age-matched controls. The age range of test subjects was 2 to 49 years (mean, 28.5). After adjustment for race and other conditions with high risk for IPD, asthma was significantly associated with increased risk of IPD (OR: 2.4; 95% CI: 1.9 to 3.1). This finding was consistent in analyses stratified for age (2 to 4 years and 5 to 17 years). Of the isolates causing IPD, 56.9% were among the 7 serotypes included in the pneumococcal conjugate vaccine, with an additional 29.1% found only in the 23-valent polysaccharide vaccine. The authors hypothesize that obstruction caused by increased production and decreased clearance of mucus and the chronic airway inflammation found in asthma are plausible etiologies for the increased risk of IPD. They conclude that consideration should be given for the addition of asthma to the list of conditions warranting pneumococcal vaccination, particularly for the younger population in the study, who are less likely to have other high-risk conditions for which vaccination is already recommended.

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Hospital “Report Cards”: Variation in the Management of Bronchiolitis

Christakis DA, Cowan CA, Garrison MM, Molteni R, Marcuse E, Zerr DM. Variation in Inpatient Diagnostic Testing and Management of Bronchiolitis. Pediatrics. 2005;115:878-4.

Bronchiolitis remains 1 of the most common causes of hospitalization in children within the first 2 years of life. In this analysis, the authors conducted a large retrospective descriptive study of infants who were admitted with bronchiolitis to children’s hospitals across the United States. The study examined the variability in length of stay (LOS), diagnostic testing, medications used, and readmission rates. The authors reviewed data on a total of 17,397 infants younger than 1 year of age. Information was obtained from the Pediatric Health Information System, which includes demographic and diagnostic data on 36 freestanding, noncompeting children’s hospitals. The authors found significant and wide variation in LOS, readmission rates, treatment approaches, and use of diagnostic tests for inpatient management of bronchiolitis.

Results indicated that 72% of patients received chest radiographs, 45% received antibiotics, and 25% received systemic steroids. The mean LOS varied considerably across hospitals, with a range of 2.40–3.90 days. The use of antibiotics varied from 28% to 62%, and the use of chest radiographs varied from 38% to 89%. There was also significant difference in readmission rates, which varied from 0% to 2.7%. The variation between hospitals remained a significant contributor even after controlling for multiple potential confounding factors.

Decreasing LOS and unnecessary medication and test utilization is supportive of pediatric patient safety initiatives. The authors suggest that chest radiographs may be leading to unnecessary use of antibiotics due to presumptive treatment based on nonspecific findings. In addition, the authors hypothesize that increased virologic testing may be cost-effective if it leads to decreased use of antibiotics.

The study concludes that there are considerable, unexplained variations that exist in the inpatient management of bronchiolitis. Development of national guidelines and controlled trials of new therapies and different approaches are indicated. Hospitals need to direct resources at analyzing and improving their inpatient care by implementing a more evidence-based approach to management of this common problem.

Maternal Group B Streptococcal Positivity: Risk factor or not?

Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. 2005;115:1240-6.

Despite implementation of intrapartum antibiotic prophylaxis (IAP) based on maternal screening for group B streptococcus (GBS) colonization, cases of early-onset neonatal GBS disease (EOGBS) continue to occur with significant morbidity and mortality. Researchers at the Brigham and Woman’s Hospital in Boston, MA devised this retrospective analysis to determine which attributes of maternal screening, provision of IAP, or evaluation of newborns for sepsis might influence the persistence of EOGBS cases. A retrospective review of all cases of culture proven EOGBS between 1997 and 2003 identified 25 cases of EOGBS among the 67,260 live births, for an overall incidence of 0.37 per 1000 live births. The incidence in infants of very low birth weight was 3.3 cases per 1,000 live births. Among the mothers of term infants with EOGBS, 14 of 17 (82%) had been screened GBS negative; 1 was GBS unknown. Eight of these 14 GBS negative mothers had at least 1 intrapartum risk factor for neonatal sepsis but did not receive IAP. The authors hypothesize that the negative GBS status in these cases may have provided a false sense of reassurance to obstetricians.

Ten of the 17 term infants were evaluated for sepsis due to clinical signs of illness, while the remaining infants were evaluated based on intrapartum risk factors alone. Interestingly, the retrospective analysis demonstrated that 5 of the 25 bacterial isolates were resistant to clindamycin and/or erythromycin, with another 5 isolates partially resistant to 1 or both of these medications. One case of EOGBS disease was found in the child of a penicillin-allergic mother who received clindamycin for IAP. This article highlights the importance of reviewing intrapartum risk factors other than GBS colonization—i.e., delivery at <37 weeks’ gestation,

 

 

intrapartum temperature >100.4°C, or signs of clinical chorioamnionitis, in addition to documenting if IAP was provided and with which antibiotic in evaluation of neonates for possible EOGBS.

Treating Refractory Kawasaki Syndrome with Infliximab

Burns JC, Mason, WH, Hauger SB, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005;146: 662-7.

Citing a 10% to 20% failure rate for intravenous immunoglobulin (IVIG) in combination with high-dose aspirin (ASA) for treating Kawasaki syndrome (KS), these authors present a case series of patients with refractory KS who were treated with infliximab. Several treatments have been suggested for KS patients with persistent or recrudescent fever after IVIG and ASA; however, no clinical trials have established an optimal treatment. Tumor necrosis factor-alpha (TNF-α) has been shown not only to be elevated in patients with KS but also to correlate with development of coronary artery aneurysms. Infliximab, a TNF-α antagonist licensed for clinical use (Remicade, Centocor, Malvern, PA), is used in several immunologic diseases with inflammation mediated by this proinflammatory cytokine. In this poorly controlled case series, 17 patients with acute KS received infliximab after at least 2 doses of IVIG (2 g/kg) and daily ASA (80–100 mg/kg/day) because they were either persistently febrile (16 patients) or had severe arthritis without fever (1 patient). Fourteen of 16 febrile patients became afebrile. C-reactive protein was lower after infliximab in all patients with elevated CRP when remeasured within 48 hours of treatment. In addition to these signs of inflammation, the researchers also studied patient outcomes.

Of 12 patients with coronary artery abnormalities before treatment with infliximab, 4 had dilatation that resolved after treatment. The remaining 8 had either aneurysms or ectasia that were unchanged after therapy. No patients in the series had complications attributed to infliximab. The authors note that the cost of treatment with infliximab compares favorably with a 2 g/kg dose of IVIG. Appropriately, they also specifically address the potential adverse effects of infliximab, for which the pharmacodynamics, pharmacokinetics and safety have not been established in children <5 years of age. Data with regard to possible complications is inadequate and comes from studies of children and adults who typically receive multiple doses of infliximab for chronic inflammatory conditions that inherently can produce multiorgan symptoms. Of note, infliximab does not carry the risk of possible infectious contamination that treatment with IVIG poses. There are several important limitations to the study that are adequately addressed by the authors. Nonetheless, the series highlights the significance of current and future randomized, controlled clinical trials defining the role of TNF-α antagonism in the treatment of KS.

Do Freestanding Children’s Hospitals Improve Care?

Merenstein D, Egleston B, Diener-West M. Lengths of stay and costs associated with children’s hospitals. Pediatrics. 2005;115: 839-44.

Adult literature has shown that access to more subspecialty oriented care results in higher costs and more procedures but does not guarantee improved outcomes. Researchers from Johns Hopkins School of Medicine and Johns Hopkins School of Public Health hypothesized that freestanding children’s hospitals would have longer lengths of stay (LOS) and higher costs compared with other hospitals with regard to similar diagnoses. To test the hypothesis, they studied 24,322 inpatient encounters for pneumonia, gastroenteritis, respiratory syncytial virus, dehydration, or asthma from the Heathcare Cost and Utilization Project Kids’ Inpatient database 2000. Of these encounters, 3,408 were from 23 different freestanding children’s hospitals, and the remaining 20,194 encounters were from 1,749 non-children’s hospitals. The children’s hospitals were all urban teaching hospitals. After adjusting for potentially confounding variables, the researchers found no significant difference in the LOS by hospital type. In this study, the median cost for an admission at a freestanding hospital was $1,294 more per hospitalization after adjustment for LOS and other potential confounder variables. In addition, the results showed that children’s hospitals were more likely to care for minority patients, patients with Medicaid, patients with multiple diagnoses, and patients transferred from other hospitals. The study design did not include direct measures of quality of care, so it is unclear if the increased cost of admission to a children’s hospital leads to improved care.

 

 

Asthma and Invasive Pneumococcal Infections

Talbot RT, Hartert TV Mitchel E, et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med. 2005; 352: 2082-90.

Current guidelines for pneumococcal vaccination exclude people with asthma, nor do the most recently published guidelines for management of asthma include pneumococcal vaccination. The authors of this study utilized public health databases to perform a nested case-controlled cohort study to determine the risk of pneumococcal disease among people with asthma. By combining a database of active surveillance for invasive pneumococcal disease (IPD) with a state-based managed healthcare program, researchers identified 635 cases of IPD in people with asthma and paired them with 6,350 age-matched controls. The age range of test subjects was 2 to 49 years (mean, 28.5). After adjustment for race and other conditions with high risk for IPD, asthma was significantly associated with increased risk of IPD (OR: 2.4; 95% CI: 1.9 to 3.1). This finding was consistent in analyses stratified for age (2 to 4 years and 5 to 17 years). Of the isolates causing IPD, 56.9% were among the 7 serotypes included in the pneumococcal conjugate vaccine, with an additional 29.1% found only in the 23-valent polysaccharide vaccine. The authors hypothesize that obstruction caused by increased production and decreased clearance of mucus and the chronic airway inflammation found in asthma are plausible etiologies for the increased risk of IPD. They conclude that consideration should be given for the addition of asthma to the list of conditions warranting pneumococcal vaccination, particularly for the younger population in the study, who are less likely to have other high-risk conditions for which vaccination is already recommended.

Hospital “Report Cards”: Variation in the Management of Bronchiolitis

Christakis DA, Cowan CA, Garrison MM, Molteni R, Marcuse E, Zerr DM. Variation in Inpatient Diagnostic Testing and Management of Bronchiolitis. Pediatrics. 2005;115:878-4.

Bronchiolitis remains 1 of the most common causes of hospitalization in children within the first 2 years of life. In this analysis, the authors conducted a large retrospective descriptive study of infants who were admitted with bronchiolitis to children’s hospitals across the United States. The study examined the variability in length of stay (LOS), diagnostic testing, medications used, and readmission rates. The authors reviewed data on a total of 17,397 infants younger than 1 year of age. Information was obtained from the Pediatric Health Information System, which includes demographic and diagnostic data on 36 freestanding, noncompeting children’s hospitals. The authors found significant and wide variation in LOS, readmission rates, treatment approaches, and use of diagnostic tests for inpatient management of bronchiolitis.

Results indicated that 72% of patients received chest radiographs, 45% received antibiotics, and 25% received systemic steroids. The mean LOS varied considerably across hospitals, with a range of 2.40–3.90 days. The use of antibiotics varied from 28% to 62%, and the use of chest radiographs varied from 38% to 89%. There was also significant difference in readmission rates, which varied from 0% to 2.7%. The variation between hospitals remained a significant contributor even after controlling for multiple potential confounding factors.

Decreasing LOS and unnecessary medication and test utilization is supportive of pediatric patient safety initiatives. The authors suggest that chest radiographs may be leading to unnecessary use of antibiotics due to presumptive treatment based on nonspecific findings. In addition, the authors hypothesize that increased virologic testing may be cost-effective if it leads to decreased use of antibiotics.

The study concludes that there are considerable, unexplained variations that exist in the inpatient management of bronchiolitis. Development of national guidelines and controlled trials of new therapies and different approaches are indicated. Hospitals need to direct resources at analyzing and improving their inpatient care by implementing a more evidence-based approach to management of this common problem.

Maternal Group B Streptococcal Positivity: Risk factor or not?

Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. 2005;115:1240-6.

Despite implementation of intrapartum antibiotic prophylaxis (IAP) based on maternal screening for group B streptococcus (GBS) colonization, cases of early-onset neonatal GBS disease (EOGBS) continue to occur with significant morbidity and mortality. Researchers at the Brigham and Woman’s Hospital in Boston, MA devised this retrospective analysis to determine which attributes of maternal screening, provision of IAP, or evaluation of newborns for sepsis might influence the persistence of EOGBS cases. A retrospective review of all cases of culture proven EOGBS between 1997 and 2003 identified 25 cases of EOGBS among the 67,260 live births, for an overall incidence of 0.37 per 1000 live births. The incidence in infants of very low birth weight was 3.3 cases per 1,000 live births. Among the mothers of term infants with EOGBS, 14 of 17 (82%) had been screened GBS negative; 1 was GBS unknown. Eight of these 14 GBS negative mothers had at least 1 intrapartum risk factor for neonatal sepsis but did not receive IAP. The authors hypothesize that the negative GBS status in these cases may have provided a false sense of reassurance to obstetricians.

Ten of the 17 term infants were evaluated for sepsis due to clinical signs of illness, while the remaining infants were evaluated based on intrapartum risk factors alone. Interestingly, the retrospective analysis demonstrated that 5 of the 25 bacterial isolates were resistant to clindamycin and/or erythromycin, with another 5 isolates partially resistant to 1 or both of these medications. One case of EOGBS disease was found in the child of a penicillin-allergic mother who received clindamycin for IAP. This article highlights the importance of reviewing intrapartum risk factors other than GBS colonization—i.e., delivery at <37 weeks’ gestation,

 

 

intrapartum temperature >100.4°C, or signs of clinical chorioamnionitis, in addition to documenting if IAP was provided and with which antibiotic in evaluation of neonates for possible EOGBS.

Treating Refractory Kawasaki Syndrome with Infliximab

Burns JC, Mason, WH, Hauger SB, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005;146: 662-7.

Citing a 10% to 20% failure rate for intravenous immunoglobulin (IVIG) in combination with high-dose aspirin (ASA) for treating Kawasaki syndrome (KS), these authors present a case series of patients with refractory KS who were treated with infliximab. Several treatments have been suggested for KS patients with persistent or recrudescent fever after IVIG and ASA; however, no clinical trials have established an optimal treatment. Tumor necrosis factor-alpha (TNF-α) has been shown not only to be elevated in patients with KS but also to correlate with development of coronary artery aneurysms. Infliximab, a TNF-α antagonist licensed for clinical use (Remicade, Centocor, Malvern, PA), is used in several immunologic diseases with inflammation mediated by this proinflammatory cytokine. In this poorly controlled case series, 17 patients with acute KS received infliximab after at least 2 doses of IVIG (2 g/kg) and daily ASA (80–100 mg/kg/day) because they were either persistently febrile (16 patients) or had severe arthritis without fever (1 patient). Fourteen of 16 febrile patients became afebrile. C-reactive protein was lower after infliximab in all patients with elevated CRP when remeasured within 48 hours of treatment. In addition to these signs of inflammation, the researchers also studied patient outcomes.

Of 12 patients with coronary artery abnormalities before treatment with infliximab, 4 had dilatation that resolved after treatment. The remaining 8 had either aneurysms or ectasia that were unchanged after therapy. No patients in the series had complications attributed to infliximab. The authors note that the cost of treatment with infliximab compares favorably with a 2 g/kg dose of IVIG. Appropriately, they also specifically address the potential adverse effects of infliximab, for which the pharmacodynamics, pharmacokinetics and safety have not been established in children <5 years of age. Data with regard to possible complications is inadequate and comes from studies of children and adults who typically receive multiple doses of infliximab for chronic inflammatory conditions that inherently can produce multiorgan symptoms. Of note, infliximab does not carry the risk of possible infectious contamination that treatment with IVIG poses. There are several important limitations to the study that are adequately addressed by the authors. Nonetheless, the series highlights the significance of current and future randomized, controlled clinical trials defining the role of TNF-α antagonism in the treatment of KS.

Do Freestanding Children’s Hospitals Improve Care?

Merenstein D, Egleston B, Diener-West M. Lengths of stay and costs associated with children’s hospitals. Pediatrics. 2005;115: 839-44.

Adult literature has shown that access to more subspecialty oriented care results in higher costs and more procedures but does not guarantee improved outcomes. Researchers from Johns Hopkins School of Medicine and Johns Hopkins School of Public Health hypothesized that freestanding children’s hospitals would have longer lengths of stay (LOS) and higher costs compared with other hospitals with regard to similar diagnoses. To test the hypothesis, they studied 24,322 inpatient encounters for pneumonia, gastroenteritis, respiratory syncytial virus, dehydration, or asthma from the Heathcare Cost and Utilization Project Kids’ Inpatient database 2000. Of these encounters, 3,408 were from 23 different freestanding children’s hospitals, and the remaining 20,194 encounters were from 1,749 non-children’s hospitals. The children’s hospitals were all urban teaching hospitals. After adjusting for potentially confounding variables, the researchers found no significant difference in the LOS by hospital type. In this study, the median cost for an admission at a freestanding hospital was $1,294 more per hospitalization after adjustment for LOS and other potential confounder variables. In addition, the results showed that children’s hospitals were more likely to care for minority patients, patients with Medicaid, patients with multiple diagnoses, and patients transferred from other hospitals. The study design did not include direct measures of quality of care, so it is unclear if the increased cost of admission to a children’s hospital leads to improved care.

 

 

Asthma and Invasive Pneumococcal Infections

Talbot RT, Hartert TV Mitchel E, et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med. 2005; 352: 2082-90.

Current guidelines for pneumococcal vaccination exclude people with asthma, nor do the most recently published guidelines for management of asthma include pneumococcal vaccination. The authors of this study utilized public health databases to perform a nested case-controlled cohort study to determine the risk of pneumococcal disease among people with asthma. By combining a database of active surveillance for invasive pneumococcal disease (IPD) with a state-based managed healthcare program, researchers identified 635 cases of IPD in people with asthma and paired them with 6,350 age-matched controls. The age range of test subjects was 2 to 49 years (mean, 28.5). After adjustment for race and other conditions with high risk for IPD, asthma was significantly associated with increased risk of IPD (OR: 2.4; 95% CI: 1.9 to 3.1). This finding was consistent in analyses stratified for age (2 to 4 years and 5 to 17 years). Of the isolates causing IPD, 56.9% were among the 7 serotypes included in the pneumococcal conjugate vaccine, with an additional 29.1% found only in the 23-valent polysaccharide vaccine. The authors hypothesize that obstruction caused by increased production and decreased clearance of mucus and the chronic airway inflammation found in asthma are plausible etiologies for the increased risk of IPD. They conclude that consideration should be given for the addition of asthma to the list of conditions warranting pneumococcal vaccination, particularly for the younger population in the study, who are less likely to have other high-risk conditions for which vaccination is already recommended.

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