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Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia
COMPLICATIONS IN INFANTS HOSPITALIZED FOR BRONCHIOLITIS OR RESPIRATORY SYNCYTIAL VIRUS PNEUMONIA DOUGLAS F. WILLSON, MD, CHRISTOPHER P. LANDRIGAN, MD, MPH, SUSAN D. HORN, PHD, AND RANDALL J. SMOUT, MS
Objective
To characterize complications among infants hospitalized for bronchiolitis or respiratory syncytial virus (RSV).
Study design
Retrospective data from 684 infants with bronchiolitis or RSV pneumonia, #1 year old, admitted to 10 children’s hospitals from April 1995 to September 1996. Outcomes included complication rates and effects on hospital and pediatric intensive care unit (PICU) length of stay (LOS) and hospital costs.
Results Most infants (79%) had one or more complication, with serious complications in 24%. Even minor complications were associated with significantly longer PICU and hospital LOS and higher costs (P < .001). Respiratory complications were most frequent (60%), but infectious (41%), cardiovascular (9%), electrolyte imbalance (19%), and other complications (9%) were common. Complication rates were higher in former premature infants (87%), infants with congenital heart disease (93%), and infants with other congenital abnormalities (90%) relative to infants without risk factors (76%). Infants 33 to 35 weeks gestational age (GA) had the highest complication rates (93%), longer hospital LOS, and higher costs (P < .004) than other former premature infants. Conclusions Complications were common in infants hospitalized for bronchiolitis or RSV pneumonia and were associated with longer LOS and higher costs. Former premature infants and infants with congenital abnormalities are at significantly greater risk for complications. Broader use of RSV prevention should be considered for these higher-risk infants. (J Pediatr 2003;143:S142-S149)
iral lower respiratory illness (VLRI) is the leading cause of hospitalization in infants.1-3 Respiratory syncytial virus (RSV) is the most common causative agent,4 but parainfluenza, influenza, adenovirus, rhinovirus, as well as others can present similarly.5 Although VLRI is generally self-limited, infants ill enough to require hospitalization are at risk for significant complications from their disease and adverse events secondary to inpatient treatment. To better characterize these complications, we reviewed the medical records of a random sample of infants, age #1 year, admitted to each of 10 children’s hospitals for bronchiolitis or RSV pneumonia over an 18-month period. We also examined the relation of comorbidity to the incidence of complications and the impact of complications on hospital length of stay (LOS) and costs.
V
METHODS We conducted a retrospective cohort study of a random sample of 100 infants with the diagnosis bronchiolitis from each of 10 children’s medical centers. These cases had been previously identified as part of a larger study of 16,506 pediatric hospital admissions from April 1, 1995, to September 30, 1996.6-8 Diagnostic codes included in this study were bronchiolitis (International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code 466.1) and RSV pneumonia (480.1).9 Exclusion criteria included age
CHD CPR DRG ECMO GA GI
S142
Congenital heart disease Cardiopulmonary resuscitation Diagnosis-related groups Extracorporeal membrane oxygenation Gestational age Gastrointestinal
ICD-9-CM LOS PICU RSV UTI VLRI
International Classification of Diseases, 9th revision, Clinical Modification Length of stay Pediatric intensive care unit Respiratory syncytial virus Urinary tract infection Viral lower respiratory illness
From PICU and the Division of Pediatric Critical Care, University of Virginia Children’s Medical Center, Charlottesville, Virginia; Children’s Hospital Inpatient Pediatrics Service, Boston, Massachusetts; Institute for Clinical Outcomes Research, International Severity Information Systems (ISIS, Inc), the Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City, Utah. Supported by a grant from AHCPR (contract No. 290-95-0042) and directed by International Severity Information Systems, Inc (ISIS), Salt Lake City, Utah. MedImmune (Gaithersburg, Md) supplied additional funding for the investigation of bronchiolitis and RSV complications. Reprint requests: Susan D. Horn, PhD, Institute for Clinical Outcomes Research, 699 East South Temple, Suite 100, Salt Lake City, UT 841021282. E-mail: [email protected]. Copyright ª 2003 Mosby, Inc. All rights reserved. 0022-3476/2003/$30.00 + 0 10.1067/S0022-3476(03)00514-6
>12 months. Risk factors specifically examined included congenital heart disease (CHD, diagnosis codes 416.8, 424.0, 424.2, 425.4, 427.89, 429.3, and 745.0-747.3), a history of preterm birth (gestational age [GA] #35 weeks), and any additional ICD-9 codes for congenital malformations or diseases (diagnosis codes 242.9-279.3, 282.5-288.8, 343.9-389.9, 478.31-478.74, 570.0-573.3, 741.02-759.89, V08-V13.7). All data collection was retrospective, and every patient’s record was completely reviewed from admission to discharge through the use of a structured framework. The institutional review boards of each participating institution exempted the study from requiring informed consent because of its observational design and commitment to patient confidentiality. Results of testing for RSV or other viruses were taken from physician’s notes or laboratory reports. For the purpose of this study, patients were categorized as RSV positive, RSV negative, or not tested, even though other viral testing may have been performed.
Data Extraction Data were extracted from two sources: hospital administrative and financial data bases and patients’ medical records.
Data Base Extraction Patient name, birth date, sex, admission and discharge dates, Pediatric Intensive Care Unit (PICU) admission and discharge dates, discharge disposition, Diagnosis-Related Groups (DRG) code, and ICD-9-CM diagnostic and procedure codes were extracted for each patient and submitted directly on electronic media to ISIS, Inc, from hospital data bases at each site. Fully allocated total costs for each patient excluding physician’s fees were also obtained. Financial representatives from each institution met through telephone conference calls to standardize the definition of what to include in the cost data sent. Cost outliers (< $400/day and >$13,000/day) and transferred patients were excluded. One site did not record these data in a similar format, and their costs were excluded from cost analysis.
Patient Medical Records Trained chart abstractors collected information on clinical findings, laboratory results, interventions, and outcomes from the medical records. Every patient’s record was completely reviewed from admission to discharge. All data were entered into a database by means of a software program developed for this purpose by ISIS, Inc, and subsequently directly transferred into a SAS database for analysis. To ensure uniformity in chart abstraction, data collectors at each institution first underwent a 3-day training session with instructors from ISIS. After returning to their own institutions, each abstractor sent photocopies of 4 charts that they had reviewed along with corresponding clinical summary reports to a member of the training team. Photocopied charts were then abstracted independently by a member of the training team Complications in Infants Hospitalized for Bronchiolitis or Respiratory Syncytial Virus Pneumonia
responsible for reliability, and the results were compared. Nine of the 10 institutions achieved a 95% or better agreement rate after the first reliability test. After a review session with the data collector from the 10th institution, a second reliability test resulted in reliability scores at or above the desired 95% agreement rate. Reliability testing was repeated when data collection was at least 50% complete. Each data collector performed well, achieving at least a 95% agreement rate.
Complications Two pediatricians reviewed clinical criteria from each patient and defined and agreed on the definitions of complications and designation of major and minor. The list of 35 complications identified for the study infants is shown in Table I. These include respiratory, infectious, cardiovascular, electrolyte, and other complications. Specific treatments (eg, cardiopulmonary resuscitation [CPR] or intubation), diagnosis codes, laboratory tests, radiographic findings, culture results, vital signs, or signs, symptoms, or physical findings were used to define each complication. Major complications included respiratory failure, apneic episodes, pneumothorax, sepsis, hypotension/shock, CPR, and seizures.
Statistical Analysis Descriptive statistics (mean, standard deviation, median, percent) were used to describe study variables by various categories. Patient (age in months) and outcome variables (hospital and PICU LOS and costs) for infants with and without specified types of risk factors and specified complications were compared by means of v2 tests for discrete data and nonparametric Wilcoxon tests (for 2-sample comparisons) or Kruskal-Wallis analysis of variance tests (for $3-sample comparisons) for continuous data to account for possible nonnormal distributions of LOS and cost. In addition, multivariate models that included demographics, risk factors, individual respiratory complications, and classes of other complications (cardiac, infectious, electrolyte, and other) were built to determine independent associations between complications and LOS and costs. Prematurity was defined by four GA groups: #32 weeks, 33 to 35 weeks, 36 weeks, and $37 weeks, based on data recorded in the medical record and missing for infants without data. Sensitivity analyses were performed by either varying the definitions of the premature infant groupings (grouping 32 weeks GA infants with 33 to 35 weeks GA infants) or comparing findings for RSV+ versus not tested and RSV-infants.
RESULTS Demographics The study sample consisted of 684 infants #1 year of age who were hospitalized for bronchiolitis or RSV pneumonia as a principal (n = 612) or secondary (n = 72) diagnosis over an 18-month study period in 10 children’s medical centers. RSV was the most common causative agent, identified S143
Table I. Complications in 684 infants with bronchiolitis or RSV pneumonia Complication Respiratory Respiratory failure Apneic episodes Stridor Hemoptysis Infiltrates/atelectasis Hyperinflation Pneumothorax Pleural effusion Infectious Otitis media Bacterial pneumonia Aspiration pneumonia Sepsis/bacteremia UTI Meningitis (S pneumoniae) Diarrhea (5 due to rotavirus) Thrush/diaper rash Cardiovascular Hypotension/inotrope use/shock Cardiac arrhythmias Cardiopulmonary resuscitation Electrolyte Hyponatremia (Na+ <130) Hypokalemia (K+ <3.5) Hyperkalemia (K+ >6.0) Hypocalcemia (Ca2+ <8.0) Hypercalcemia (Ca2+ >11) Hypoglycemia (glucose <40) Hyperglycemia (glucose >200) Metabolic acidosis (HCO3 <16) Metabolic alkalosis (HCO3 >30) Other Adverse drug reaction Anemia Seizure Coagulopathy Vocal cord injury GI bleeding Hyperbilirubinemia
No. of patients
Percent
96 60 9 1 293 142 4 3
14.0 8.8 1.3 0.2 42.8 20.8 0.6 0.4
173 52 1 40 8 1 14 49
25.3 7.6 0.2 5.9 1.2 0.2 2.1 7.2
37 17 6
5.4 2.5 0.9
4 45 69 9 1 2 17 14 32
0.6 6.6 10.1 1.3 0.2 0.3 2.5 2.1 4.7
6 41 12 4 1 1 10
0.9 6.0 1.8 0.6 0.2 0.2 1.5
with 83% of 505 children tested having a positive test for RSV (26% were not tested). The average age was 3.4 ± 3.2 months, and 58% were male.
Outcomes Outcomes were generally good. The overwhelming majority of infants (98%) were discharged to home, and there was only 1 death. This child had coarctation of the aorta, presented with shock, and failed to recover despite extracorS144 Willson et al
poreal membrane oxygenation (ECMO). Two children were discharged to skilled nursing care facilities, although both appeared to be recovering without sequelae. Four children were transferred to other institutions before discharge, 2 after a hospitalization of <48 hours. Eight children were discharged with home health care. About one third (31%) of children were admitted to intensive care. The average hospital LOS was 5.0 ± 5.5 days; average PICU LOS was 5.2 ± 6.7 days; and average hospital costs were $9063 ± $13,220 (adjusted to year 2000 dollars).
Complications: Frequency and Bivariate Associations with LOS and Costs Despite the generally good outcomes, complications were common. We defined 35 complications for the purpose of this study (Table I). The majority of infants (n = 543, 79.4%) had 1 or more complications: 218 infants had one complication, 152 had two complications, and 173 had 3 to 11 complications. Most complications were not serious (n = 379, 55.4% had only minor complications), but overall the presence of complications was significantly associated with longer hospital and PICU LOS and higher costs (Table II). Infants with minor complications only had on average 1 day longer hospital LOS (P < .0001), 0.8 days longer PICU LOS (P = .016), and $1650 higher cost (P = .001) compared with infants with no complications. Infants with major complications (n = 164, 24%) had on average 7.3 days longer hospital LOS, 6.5 days longer PICU LOS, and $18,650 higher cost (P < .0001) compared with infants with no complications. As would be expected, respiratory complications were the most frequent, and the presence of any respiratory complication was significantly associated with an increase in hospital costs and LOS (P < .0001) (Table II). Infants with respiratory complications only (n = 146) and infants with both respiratory and nonrespiratory complications (n = 264) had significantly longer hospital and PICU LOS and cost significantly more than infants with no complications (P # .003). Infants with nonrespiratory complications only (n = 133) had significantly longer hospital and PICU LOS (P # .005) but not significantly higher costs (P = .65) compared with infants with no complications. Overall, 96 (14%) infants required mechanical ventilation either for apnea or respiratory failure. These infants were generally younger than those with no complications (1.6 vs 3.7 months, respectively, P < .0001; Table II). Mechanical ventilation was significantly more likely to occur in premature infants (28.7%), those with CHD (31.7%), or those with other congenital abnormalities (37.3%) than in infants with no risk factors (9.1%; P < .0001). The development of respiratory failure was associated with a 5-times increase in LOS and a 9-times increase in hospital costs. Apnea, the presence of radiographic infiltrates/atelectasis, and hyperinflation on radiography were also associated with significant increases in LOS and costs (P < .0003). Stridor was reported in 9 children; 5 in association with mechanical ventilation. Pneumothorax was seen in 4 (0.6%) and pleural effusions in 3 (0.4%) patients. The Journal of Pediatrics November 2003
Table II. Association of complications with hospital resource use Complication
Hospital LOS
PICU LOS
Costs
Age (mo)
3484 ± 2169 (3078) 10,399 ± 14,364 (4899) P < .0001 6293 ± 6273 (4095) P < .0001 4217 ± 4639 (3013) P = .65 15,640 ± 18,229 (8962) P < .0001
3.7 ± 3.1 (3.0) 3.4 ± 3.2 (2.0) P = .05 2.8 ± 2.9 (2.0) P = .002 4.4 ± 3.6 (4.0) P = .24 3.2 ± 3.1 (2.0) P = .02
12,367 ± 15,789 (6,475) P < .0001 31,481 ± 21,382 (25,909) P < .0001 20,242 ± 20,745 (12,824) P < .0001 14,453 ± 17,080 (7686) P < .0001 9205 ± 11,849 (4728) P < .0001 9012 ± 15,431 (4182) P < .0001 6274 ± 11,422 (3496) P = .02 9455 ± 12,296 (5474) P < .0001 26,410 ± 31,704 (14,726) P < .0001 27,149 ± 23,238 (20,445) P < .0001 28,699 ± 24,847 (26,003) P < .0001 20,610 ± 15,302 (20,167) P < .0001 24,700 ± 22,841 (18,714) P < .0001 20,667 ± 12,510 (18,609) P < .0001 25,348 ± 27,029 (14,104) P < .0001 24,872 ± 29,274 (14,094) P < .0001
3.0 ± 3.1 (2.0) P = .003 1.6 ± 1.9 (1.0) P < .0001 1.8 ± 2.3 (1.0) P < .0001 2.9 ± 3.0 (2.0) P = .001 3.4 ± 3.3 (2.0) P = .17 4.2 ± 3.5 (3.0) P = .27 5.1 ± 3.6 (4.0) P = .002 4.4 ± 3.5 (4.0) P = .33 1.9 ± 1.7 (1.5) P = .0007 2.3 ± 2.4 (1.0) P = .001 2.6 ± 2.7 (2.0) P = .04 1.8 ± 2.1 (1.0) P = .006 2.4 ± 2.5 (2.0) P < .0001 1.8 ± 1.5 (1.0) P = .03 2.4 ± 2.7 (2.0) P = .001 2.8 ± 2.6 (2.0) P = .06
Mutually exclusive groups No complications Any complication
n = 141 n = 543
Respiratory complications only Non-respiratory complications only Both respiratory and nonrespiratory complications
n = 146 n = 133 n = 264
2.7 ± 1.5 (2.0) 5.6 ± 5.9 (4.0) P < .0001 3.9 ± 2.8 (3.0) P < .0001 3.2 ± 1.8 (3.0) P = .003 7.7 ± 7.6 (5.0) P < .0001
1.1 ± 0.9 (0.8) 5.6 ± 6.9 (3.7) P < .0001 3.0 ± 2.9 (1.9) P = .003 2.0 ± 1.0 (2.2) P = .005 6.9 ± 7.8 (4.8) P < .0001
Non–mutually exclusive groups Any respiratory complication Respiratory failure
n = 410 n = 96
Apnea n = 60 Atelectasis/infiltrates n = 293 Hyperinflation n = 142 Any infectious complication n = 280 Otitis media n = 173 Bacterial pneumonia n = 52 Sepsis/bacteremia n = 40 Any cardiovascular complication Hypotension and/or inotrope Cardiac arrhythmias
n = 61 n = 37 n = 17
Any electrolyte complication Metabolic acidosis
n = 132 n = 14
Other complications n = 64 Anemia n = 41
6.3 ± 6.6 (4.0) P < .0001 13.5 ± 9.6 (11.0) P < .0001 9.8 ± 8.5 (7.5) P < .0001 7.1 ± 6.9 (5.0) P < .0001 5.0 ± 4.6 (4.0) P < .0001 5.3 ± 6.8 (3.0) P < .0001 4.1 ± 5.3 (3.0) P < .0001 5.7 ± 6.1 (3.5) P < .0001 12.2 ± 13.8 (7.0) P < .0001 11.6 ± 10.3 (9.0) P < .0001 10.8 ± 10.8 (8.0) P < .0001 10.5 ± 7.9 (9.0) P < .0001 10.3 ± 9.5 (8.0) P < .0001 10.1 ± 5.8 (9.5) P < .0001 10.8 ± 11.5 (7.5) P < .0001 10.1 ± 11.6 (7.0) P < .0001
6.0 ± 7.1 (3.9) P < .0001 9.0 ± 8.2 (6.9) P < .0001 7.5 ± 7.1 (4.9) P < .0001 6.4 ± 6.8 (4.5) P < .0001 4.3 ± 4.4 (2.9) P = .0003 6.4 ± 9.8 (3.0) P < .0001 4.3 ± 9.1 (1.9) P = .007 4.9 ± 6.3 (1.8) P = .009 11.4 ± 13.9 (5.1) P < .0001 8.9 ± 8.7 (7.0) P < .0001 8.2 ± 9.2 (7.0) P < .0001 7.5 ± 5.8 (6.9) P < .0001 8.6 ± 8.9 (6.6) P < .0001 7.1 ± 4.8 (6.4) P < .0001 9.3 ± 11.1 (6.5) P < .0001 9.6 ± 11.4 (6.5) P < .0001
For hospital LOS (days), PICU LOS (days), costs ($), and age in months, table values are mean ± SD (median). The means in each row are compared with the no complications group, using nonparametric 2-sample Wilcoxon tests.
Overall, only 15% of the radiographs taken were interpreted as normal. Infectious complications were the second most common (40.9%) and as a group were associated with significant increases in LOS and costs (P < .0001) (Table II). Otitis Complications in Infants Hospitalized for Bronchiolitis or Respiratory Syncytial Virus Pneumonia
media was diagnosed in 173 (25.3%), most often in children without risk factors (28.3% vs #18.4% in infants with risk factors, P # .07) and was significantly associated with increased LOS and costs (P # .02). Bacterial pneumonia, as evidenced by either a secondary ICD-9 code or stated rationale S145
for use of antibiotics, was identified in 52 (7.6%) infants. An ICD-9 code for sepsis/bacteremia was present in 40 (5.9%) patients, although only 14 positive blood cultures were reported, 10 of which were coagulase-negative staphylococcus. These infants were younger than those with no complications (1.9 vs 3.7 months, P = .0007) and were more likely than infants without sepsis to have a congenital abnormality (22.5% vs 7.8%; P = .001), to be on mechanical ventilation (47.5% vs 12%; P < .0001), and to have indwelling arterial or central venous catheters (27.5% vs 6.8%; P < .0001). The diagnoses of either bacterial pneumonia or sepsis were associated with significantly greater costs and LOS (P < .009). Eight infants carried the diagnosis of urinary tract infection (UTI), although only 3 positive urine cultures were documented. Meningitis (S pneumoniae) was identified in one 9-month-old infant. Gastroenteritis or diarrhea developed in 14 infants, 5 of whom had rotavirus identified. Thrush or diaper rash was diagnosed in 49 (7.2%) infants. Antibiotics were used in 465 (68%) of all infants. Electrolyte disturbances were common. Although these are in general considered to be of little consequence, as a group they were associated with more than a 3-times increase in LOS and 7-times increase in costs (Table II). Hypokalemia (K+ < 3.5) was noted in 45 (6.6%) patients and metabolic alkalosis (HCO3 >30) in 32 (4.7%) patients. Both hypokalemia and metabolic alkalosis were strongly correlated with use of furosemide (P < .0001). Hyperkalemia was also common (n = 69, 10%). We suspect much of this might be related to difficulty with blood sampling in small infants (with the likelihood that many samples were obtained by ‘‘heel stick’’). Hyponatremia was reported in 4 infants, hypocalcemia in 9, and hypercalcemia in 1. Hypoglycemia ( < 40) was noted in 2 infants; hyperglycemia (>200) was reported in 17. Fourteen children had significant metabolic acidosis defined as HCO3 < 16. Two of these children also required CPR, 3 received inotropes, and 8 had respiratory failure and were on mechanical ventilation. Cardiac dysfunction is not generally thought to be a common feature of bronchiolitis or RSV, but the ICD-9 code for shock was reported in 5 infants, and 35 infants were treated with inotropes during their hospital stay. Arrhythmias were described in 17 children, but most were PVCs or PACs. Two children had ventricular tachycardia. Cardiovascular complications were significantly more common in infants with CHD (51.2%) and in infants with other congenital anomalies (22.0%) than in infants with no risk factors (5.4%) (P < .0001). Six children required CPR. Two of these children had underlying cardiac defects (both coarctation of the aorta), two had airway anomalies, and one was septic. In all cases, CPR was associated with respiratory failure and the need for ventilatory support. One child died, but the others were successfully resuscitated. Miscellaneous complications included anemia, seizures, adverse drug reactions, frank hemoptysis, hyperbilirubinemia, vocal cord injury, and GI hemorrhage. Anemia, defined by hematocrit <25% or hemoglobin <8, occurred in 41 (6.0%) patients. These children were borderline younger (P = .06), but they were not more likely to be premature than patients without S146 Willson et al
anemia (P = .39) or without risk factors (P = .20). Although anemia was significantly associated with the presence of an arterial and/or central venous catheter (P < .0001), still, 61% of infants with anemia did not have a line. Anemia was associated with a longer LOS (10.1 vs 2.7 days; P < .0001) and more than a 7-times increase in hospital costs ($24,872 vs $3484, Table II). Twelve infants carried a diagnosis of seizures and manifested seizures during their hospitalization; one had an episode of status. Six adverse drug reactions were reported but were not further characterized in the records. The child with hemoptysis mentioned above was the single patient who died. Before death, this child had multiple problems including respiratory failure, infection, coagulopathy, and treatment with ECMO. Among the 10 children with hyperbilirubinemia, 4 were considered to have physiologic jaundice, 1 Rh incompatibility, 3 were related to sepsis, and 2 were mild and present on admission. The cause of vocal cord injury in one child was unclear. There was only one instance of GI hemorrhage.
Risk Factors Although the majority (n = 516, 75.4%) of the infants had no significant health problems (significant risk factors), 87 (12.7%) were former premature infants (#35 weeks GA), 41 (6.0%) had CHD, and 59 (8.6%) had other congenital problems ranging from metabolic abnormalities to cleft palate (Table III). Infants with congenital abnormalities other than CHD tended to be older (average age, 4.5 vs 3.4 months, respectively, P = .04), but the risk factor groups otherwise did not differ demographically. The frequency of complications, LOS, and costs tended to be significantly higher for infants with risk factors (Table III) compared with infants with no risk factors recorded. Infants with risk factors were significantly more likely to have respiratory complications (71.3%-81.4%) than those with no risk factors (55.8%) (P # .03). Also, infants with risk factors were significantly more likely to have electrolyte complications (31.0%-39.0%) than those with no risk factors (14.9%) (P # .0006). Infectious complications were less common in children with CHD than in children without risk factors (22.0% vs 42.8%; P = .008). Degree of prematurity was significantly associated with complications. Former preterm infants of 33 to 35 weeks GA had the highest rates of complications (93.0%), longest hospital LOS (7.4 days), and highest costs ($14,137) (Table IV). There were significant differences in the age at hospital admission among the GA groups, and the 33 to 35 GA infants were the youngest (2.7 vs >3.0 months for other groups; P < .0001). When we deleted the 32 weeks GA infants from the #32 weeks GA group and combined them with the 33 to 35 weeks GA infants, the previous significant differences shown in Table IV in complication rates, hospital LOS, and costs were fundamentally similar, with the 32 to 35 weeks GA group having the highest rates of complications, longest average hospital LOS, and highest average costs. When the same analyses were performed on the RSV+ subsample (n = 417 infants), all the same patterns of hospital resource use and complications remained. The Journal of Pediatrics November 2003
Table III. Association of risk factors with complications and hospital resource use Risk group No risk factors Congenital heart disease Other congenital abnormalities Premature
% Complications
Hospital LOS
PICU LOS
Costs
76.5% 92.7% P = .02 89.8% P = .02 87.4% P = .02
4.0 ± 3.9 (3.0) 7.7 ± 5.9 (6.0) P < .0001 10.7 ± 10.9 (8.0) P < .0001 6.7 ± 5.8 (4.0) P < .0001
4.2 ± 5.2 (2.5) 5.1 ± 3.4 (4.1) P = .03 9.1 ± 11.9 (5.8) P = .002 5.7 ± 5.0 (4.6) P = .038
6823 ± 9924 (3777) 16,644 ± 15,308 (11,335) P < .0001 21,426 ± 25,296 (13,241) P < .0001 12,634 ± 12,952 (7376) P < .0001
n = 516 n = 41 n = 59 n = 87
For hospital LOS (days), PICU LOS (days), costs ($), and age in months, table values are mean ± SD (median). The means in each row are compared with the no risk factors group, using nonparametric 2-sample Wilcoxon tests. The percentages in the comorbidity groups are compared with the no risk factors group, using Fisher exact tests.
Table IV. Association of GA with complications and hospital resource use
Any complications Hospital LOS PICU LOS Cost Age in mo
n = 543
#32 wk GA n = 44
33–35 wk GA n = 43
36 wk GA n = 46
$37 wk GA n = 338
GA missing n = 213
81.8% (36) 6.1 ± 5.1 (4.0) 4.7 ± 4.5 (3.9) 11,015 ± 9752 (7339) 3.8 ± 3.1 (3.0)
93.0% (40) 7.4 ± 6.5 (5.0) 6.7 ± 5.4 (5.0) 14,137 ± 5309 (8129) 2.7 ± 2.5 (2.0)
82.6% (38) 6.0 ± 8.0 (3.5) 8.4 ± 9.7 (4.5) 11,118 ± 18,504 (5741) 3.0 ± 3.2 (1.5)
81.7% (276) 4.5 ± 4.6 (3.0) 4.4 ± 6.4 (2.5) 8055 ± 12,007 (3903) 3.1 ± 3.2 (2.0)
71.8% (153) 4.8 ± 5.7 (3.0) 5.3 ± 7.3 (3.1) 8716 ± 13,646 (4055) 4.2 ± 3.3 (3.0)
P value P = .008* P = .004y P = .045y P = .002y P < .0001y
For the first row, table values are percent (number of infants). For hospital LOS (days), PICU LOS (days), costs ($), and age in months, table values are mean ± SD (median). *The P value is from a v2 test of a 5 3 2 contingency table. yMeans compared by nonparametric Kruskal-Wallis tests.
Multivariate Associations Between Complications, Risk factors, LOS, and Costs Linear regression controlling for age, sex, and risk factors confirmed the importance of both respiratory and nonrespiratory complications as predictors of increased LOS and costs. Individual respiratory complications of respiratory failure, atelectasis, pneumothorax, stridor, apnea, and hyperinflation were independently entered into the model, and each (with the exception of apnea) independently predicted increases in LOS and costs. To simplify model-building, nonrespiratory complications were entered into the model in groups, including cardiovascular, infectious, electrolyte, and other. Each of these groups of complications independently predicted increases in LOS and costs. In addition, having a noncardiac congenital abnormality predicted increases in LOS and costs. Altogether, the resulting models explained R2 = 64% of the variation in LOS and R2 = 73% of the variation in cost for patients admitted with VLRI infections.
DISCUSSION Complications were common in infants hospitalized for bronchiolitis or RSV and occurred disproportionately in infants with underlying congenital abnormalities or preComplications in Infants Hospitalized for Bronchiolitis or Respiratory Syncytial Virus Pneumonia
maturity. Although many could be considered minor, even minor complications and complications as common as electrolyte imbalance were associated with significant increases in hospital LOS and costs. Serious complications affected 24% of the infants and were associated with large and highly significant increases in hospital resource use. Respiratory complications were the most common and among the most serious. They were more frequent in former preterm infants, not surprising, given their smaller size and proportionately smaller airways. The greater risk of respiratory complications also extended to children with congenital abnormalities, but the variety of diagnoses precluded identifying a single unifying cause. The development of respiratory failure and consequent need for respiratory support greatly escalates the use of other supportive measures (eg, sedation, monitoring lines, and laboratory measurements). It is therefore not surprising that respiratory complications were associated with longer LOS and higher average hospital costs. Although respiratory complications are anticipated as part of the underlying disease, the cardiovascular complications reported here are somewhat unexpected. There were many minor arrhythmias (eg, PACs and PVCs) but two cases of ventricular tachycardia. One was clearly associated with administration of nebulized albuterol (and stopped when the S147
drug was stopped) and the other was a child with coarctation of the aorta who had undergone cardiac repair at that hospitalization. Other cardiovascular complications such as shock, use of inotropic support, or need for CPR are also not generally thought to accompany VLRI. The majority of infants in this study were infected with RSV, and RSV is not known to spread beyond the respiratory tract (eg, there is no viremic phase of infection).10 Although case reports of ventricular dysrhythmias and cardiogenic shock with RSV infection have been published,11,12 there is little evidence that RSV infection causes myocarditis or primary cardiac dysfunction. Most (57%) of the patients with shock/inotrope use were on positive-pressure ventilation, 13 had some form of CHD, and 5 had the complication of sepsis. Thus, relative hypovolemia in the face of positive-pressure ventilation or secondary myocardial dysfunction from CHD or sepsis would seem more likely explanations for hypotension or need for inotropic support than primary myocardial dysfunction from RSV infection. Additionally, since half of the inotrope use was in a single institution, physician preference might also have played a role. Infectious complications were also common but probably were overdiagnosed. Otitis media is well described in VLRI but may not always represent bacterial superinfection.13,14 Similarly, the diagnosis of bacterial pneumonia in the face of bronchiolitis or RSV infection is extremely difficult. Fever, pulmonary infiltrates, positive tracheal aspirate cultures, and elevated WBCs are common, and their presence does not distinguish bacterial from viral causation. The infectious complication of most concern was sepsis or bacteremia, because this was associated with more than a 4-times increase in LOS and more than 7-times increase in costs. Forty patients were identified with sepsis or bacteremia, although only 14 positive blood cultures were reported (10 were coagulasenegative staphylococcus). Although a positive blood culture is not required to make the diagnosis of sepsis, it is not clear from the records how this diagnosis was made. Other investigators have found a much lower incidence of bacterial complications in VLRI.15,16 The use of broad-spectrum antibiotics in 68% of these patients undoubtedly reflects the frequency with which these infectious complications were suspected and the fragile nature of the population being cared for. The electrolyte complications are probably of little consequence from a morbidity perspective but bear mentioning because they are common and because they are associated with increased costs and LOS. Most could legitimately be considered minor. Both hypokalemia and metabolic alkalosis were strongly associated with use of furosemide. The high incidence of hyperkalemia is unexplained but probably represents the practice of collecting blood by heel stick in small infants. Hypoglycemia was rare but hyperglycemia common and probably related to steroid administration. Hyperbilirubinemia was also common but of little consequence and, in most cases, physiologic. The occurrence of metabolic acidosis is probably more concerning but was frequently associated with other problems, including sepsis and dehydration. Most of these children were relatively sick, as evidenced by the fact that the majority was on ventilators and S148 Willson et al
several required CPR and/or inotropic medications. In 6 of 14, however, metabolic acidosis was associated with nothing more than transient hypokalemia or hyperkalemia. Among the miscellaneous complications, the most common was anemia (n = 41, 6.0%). Surprisingly, these infants were not more likely to be premature or younger in age. They were, however, more likely to be in the PICU, intubated, and have indwelling invasive catheters. It is likely, therefore, that anemia in many cases was a consequence of frequent blood draws and invasive procedures. Other miscellaneous complications, including seizures, coagulopathy, hyperbilirubinemia, and hemoptysis, were either rare or of little consequence. Only 6 adverse drug reactions were reported, but prior studies have demonstrated substantial underreporting of adverse drug events.17,18 The low frequency of GI hemorrhage merits comment just because it is so low given that nearly one third of these patients were intensive care patients. The low incidence of GI hemorrhage in infants has been commented upon by other investigators.19 The association of particular complications with specific risk factors is not unanticipated but may help identify infants at risk. One surprise from our analysis, however, is the longer hospital LOS and higher costs in 33 to 35 weeks GA premature infants relative to infants born at earlier GA. This finding has not been reported previously. The higher incidence of complications and younger average age may have been important determinants of the higher LOS and costs. Age at admission has been reported previously as a risk factor for severe disease.7,20 The PICNIC study also found that infants 33 to 35 weeks GA were just as much at risk for RSV infection as infants #32 weeks GA as the result of both their prematurity and younger age at admission.20 These infants appear to have been exposed to RSV at an earlier age, possible due to more rapid discharge from the hospital or less rigorous precautions to environmental exposure. Such exposure at an earlier age leads to increased risk of severe RSV illness comparable to the risk in more premature groups. The outcome of infants with VLRI is generally good, but complications are common. The type of complication(s) is influenced by comorbid conditions; complications, even minor ones, have significant impact on resource utilization. Hospital costs to care for this group of infants approach 1 billion dollars per year in the United States. In addition to these immediate costs, rates of rehospitalization in the year after discharge exceed 20% in some studies, with >40% of infants having subsequent development of asthma.21-24 Given the high rate of complications and the possibility of long-term disability associated with bronchiolitis or RSV pneumonia, either more effective acute therapy is needed or more liberal use of preventive strategies should be considered in the high-risk groups identified in this study.
CONCLUSIONS Bronchiolitis and RSV pneumonia in infants is generally a self-limited disease, but infants ill enough to require hospitalization may have significant complications. Complications The Journal of Pediatrics November 2003
are more common in infants with preexisting medical problems and are associated with longer LOS and higher costs. It may be reasonable to consider broader use of preventive strategies in these higher-risk infants.
COMMENTS FROM THE AUDIENCE John V. Williams, MD, Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee: RSV doesn’t cause anemia. Children may have or become anemic, but RSV does not cause it.
Douglas F. Willson, MD, Associate Professor of Pediatrics and Director, Pediatric Intensive Care Unit, Children’s Medical Center, University of Virginia Health System, Charlottesville, Virginia: If an infant is hospitalized in the ICU for RSV, it is almost guaranteed that a central line is put in and the child will become anemic over time. So anemia is not directly a complication of RSV but a complication of the therapy or hospitalization for RSV or bronchiolitis.
REFERENCES 1. Hall CB, McCarthy CA. Respiratory syncytial virus. In: Mandell GL, Douglas RG Jr, Bennett JE, editors. Principles and practice of infectious diseases. 4th ed. New York (NY): Churchill Livingstone; 1995. p. 1501-19. 2. Leader S, Kohlhase K. Respiratory syncytial virus-coded pediatric hospitalizations, 1997-1999. Pediatr Infect Dis J 2002;21:629-32. 3. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 1999;282:1440-6. 4. Henderson FW, Clyde WA, Collier AM, Denny FW, Senior RJ, Sheaffer CI, et al. The etiology and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr 1979;95:183-90. 5. Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med 2001;344:1917-28. 6. Horn SD, Torres A Jr, Willson D, Dean JM, Gassaway J, Smout R. Development of a pediatric age- and disease-specific severity measure. J Pediatr 2002;141:496-503. 7. Willson DF, Horn SD, Hendley JO, Smout R, Gassaway J. The effect of practice variation on resource utilization in infants hospitalized for viral lower respiratory illness (VLRI). Pediatrics 2001;108:851-5.
Complications in Infants Hospitalized for Bronchiolitis or Respiratory Syncytial Virus Pneumonia
8. Willson DF, Horn SD, Smout RJ, Gassaway J, Torres A. Severity assessment in children hospitalized with bronchiolitis using the pediatric component of the Comprehensive Severity Index. Pediatr Crit Care Med 2000;1:127-32. 9. Horn SD, Smout RJ. Effects of prematurity on respiratory syncytial virus hospital resource use and outcomes. J Pediatr 2003;143:S133-S141. 10. Hall CB, Walsh EE, Long CE, Schnabel KC. Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis 1991;163:693-8. 11. Thomas JA, Raroque S, Scott WA, Toro-Figueroa LO, Levin DL. Successful treatment of severe dysrhythmias in infants with respiratory syncytial virus infections: Two cases and literature review. Crit Care Med 1997;25:880-6. 12. Menahem S. Respiratory syncytial virus and supraventricular tachycardia in an infant. Int J Cardiol 1991;32:249-51. 13. Chonmaitree T, Owen MJ, Patel JA, Hedgpath D, Horlick D, Howie VM. Effect of viral respiratory tract infection on outcome of acute otitis media. J Pediatr 1992;120:856-62. 14. Andrade MA, Hoberman A, Glustein J, Paradise JL, Wald ER. Acute otitis media in children with bronchiolitis. Pediatrics 1998;101:617-9. 15. Hall CB, Powell KR, Schnabel KC, Gala CL, Pincus PH. Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection. J Pediatr 1988;113:266-71. 16. Friis B, Andersen P, Brenoe E, Hornsleth A, Jensen A, Knudson FU, et al. Antibiotic treatment of pneumonia and bronchiolitis. Arch Dis Child 1984;59:1038-45. 17. Leape LL. Reporting of adverse events. N Engl J Med 2002;347: 1633-8. 18. Cullen DJ, Bates DW, Small SD, Cooper JB, Nemeskal AR, Leape LL. The incident reporting system does not detect adverse drug events: a problem for quality improvement. Jt Comm J Qual Improv 1995;21:541-8. 19. Crill CM, Hak EB. Upper gastrointestinal tract bleeding in critically ill pediatric patients. Pharmacotherapy 1999;19:162-80. 20. Law BJ, MacDonald N, Langley J, Mitchell I, Stephens D, Wang EEL, et al. Severe respiratory syncytial virus infection among otherwise healthy prematurely born infants: what are we trying to prevent? Paediatr Child Health 1998;3:402-4. 21. Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000;161:1501-7. 22. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. N Engl J Med 1995;332:133-8. 23. Noble V, Murray M, Webb MS, Alexander J, Swarbrick AS, Milner AD. Respiratory status and allergy nine to 10 years after acute bronchiolitis. Arch Dis Child 1997;76:315-9. 24. Stein RT, Sherrill D, Morgan WJ, Holberg CJ, Halonen M, Taussig LM, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 1999;354:541-5.
S149
Objective
To characterize complications among infants hospitalized for bronchiolitis or respiratory syncytial virus (RSV).
Study design
Retrospective data from 684 infants with bronchiolitis or RSV pneumonia, #1 year old, admitted to 10 children’s hospitals from April 1995 to September 1996. Outcomes included complication rates and effects on hospital and pediatric intensive care unit (PICU) length of stay (LOS) and hospital costs.
Results Most infants (79%) had one or more complication, with serious complications in 24%. Even minor complications were associated with significantly longer PICU and hospital LOS and higher costs (P < .001). Respiratory complications were most frequent (60%), but infectious (41%), cardiovascular (9%), electrolyte imbalance (19%), and other complications (9%) were common. Complication rates were higher in former premature infants (87%), infants with congenital heart disease (93%), and infants with other congenital abnormalities (90%) relative to infants without risk factors (76%). Infants 33 to 35 weeks gestational age (GA) had the highest complication rates (93%), longer hospital LOS, and higher costs (P < .004) than other former premature infants. Conclusions Complications were common in infants hospitalized for bronchiolitis or RSV pneumonia and were associated with longer LOS and higher costs. Former premature infants and infants with congenital abnormalities are at significantly greater risk for complications. Broader use of RSV prevention should be considered for these higher-risk infants. (J Pediatr 2003;143:S142-S149)
iral lower respiratory illness (VLRI) is the leading cause of hospitalization in infants.1-3 Respiratory syncytial virus (RSV) is the most common causative agent,4 but parainfluenza, influenza, adenovirus, rhinovirus, as well as others can present similarly.5 Although VLRI is generally self-limited, infants ill enough to require hospitalization are at risk for significant complications from their disease and adverse events secondary to inpatient treatment. To better characterize these complications, we reviewed the medical records of a random sample of infants, age #1 year, admitted to each of 10 children’s hospitals for bronchiolitis or RSV pneumonia over an 18-month period. We also examined the relation of comorbidity to the incidence of complications and the impact of complications on hospital length of stay (LOS) and costs.
V
METHODS We conducted a retrospective cohort study of a random sample of 100 infants with the diagnosis bronchiolitis from each of 10 children’s medical centers. These cases had been previously identified as part of a larger study of 16,506 pediatric hospital admissions from April 1, 1995, to September 30, 1996.6-8 Diagnostic codes included in this study were bronchiolitis (International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code 466.1) and RSV pneumonia (480.1).9 Exclusion criteria included age
CHD CPR DRG ECMO GA GI
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Congenital heart disease Cardiopulmonary resuscitation Diagnosis-related groups Extracorporeal membrane oxygenation Gestational age Gastrointestinal
ICD-9-CM LOS PICU RSV UTI VLRI
International Classification of Diseases, 9th revision, Clinical Modification Length of stay Pediatric intensive care unit Respiratory syncytial virus Urinary tract infection Viral lower respiratory illness
From PICU and the Division of Pediatric Critical Care, University of Virginia Children’s Medical Center, Charlottesville, Virginia; Children’s Hospital Inpatient Pediatrics Service, Boston, Massachusetts; Institute for Clinical Outcomes Research, International Severity Information Systems (ISIS, Inc), the Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City, Utah. Supported by a grant from AHCPR (contract No. 290-95-0042) and directed by International Severity Information Systems, Inc (ISIS), Salt Lake City, Utah. MedImmune (Gaithersburg, Md) supplied additional funding for the investigation of bronchiolitis and RSV complications. Reprint requests: Susan D. Horn, PhD, Institute for Clinical Outcomes Research, 699 East South Temple, Suite 100, Salt Lake City, UT 841021282. E-mail: [email protected]. Copyright ª 2003 Mosby, Inc. All rights reserved. 0022-3476/2003/$30.00 + 0 10.1067/S0022-3476(03)00514-6
>12 months. Risk factors specifically examined included congenital heart disease (CHD, diagnosis codes 416.8, 424.0, 424.2, 425.4, 427.89, 429.3, and 745.0-747.3), a history of preterm birth (gestational age [GA] #35 weeks), and any additional ICD-9 codes for congenital malformations or diseases (diagnosis codes 242.9-279.3, 282.5-288.8, 343.9-389.9, 478.31-478.74, 570.0-573.3, 741.02-759.89, V08-V13.7). All data collection was retrospective, and every patient’s record was completely reviewed from admission to discharge through the use of a structured framework. The institutional review boards of each participating institution exempted the study from requiring informed consent because of its observational design and commitment to patient confidentiality. Results of testing for RSV or other viruses were taken from physician’s notes or laboratory reports. For the purpose of this study, patients were categorized as RSV positive, RSV negative, or not tested, even though other viral testing may have been performed.
Data Extraction Data were extracted from two sources: hospital administrative and financial data bases and patients’ medical records.
Data Base Extraction Patient name, birth date, sex, admission and discharge dates, Pediatric Intensive Care Unit (PICU) admission and discharge dates, discharge disposition, Diagnosis-Related Groups (DRG) code, and ICD-9-CM diagnostic and procedure codes were extracted for each patient and submitted directly on electronic media to ISIS, Inc, from hospital data bases at each site. Fully allocated total costs for each patient excluding physician’s fees were also obtained. Financial representatives from each institution met through telephone conference calls to standardize the definition of what to include in the cost data sent. Cost outliers (< $400/day and >$13,000/day) and transferred patients were excluded. One site did not record these data in a similar format, and their costs were excluded from cost analysis.
Patient Medical Records Trained chart abstractors collected information on clinical findings, laboratory results, interventions, and outcomes from the medical records. Every patient’s record was completely reviewed from admission to discharge. All data were entered into a database by means of a software program developed for this purpose by ISIS, Inc, and subsequently directly transferred into a SAS database for analysis. To ensure uniformity in chart abstraction, data collectors at each institution first underwent a 3-day training session with instructors from ISIS. After returning to their own institutions, each abstractor sent photocopies of 4 charts that they had reviewed along with corresponding clinical summary reports to a member of the training team. Photocopied charts were then abstracted independently by a member of the training team Complications in Infants Hospitalized for Bronchiolitis or Respiratory Syncytial Virus Pneumonia
responsible for reliability, and the results were compared. Nine of the 10 institutions achieved a 95% or better agreement rate after the first reliability test. After a review session with the data collector from the 10th institution, a second reliability test resulted in reliability scores at or above the desired 95% agreement rate. Reliability testing was repeated when data collection was at least 50% complete. Each data collector performed well, achieving at least a 95% agreement rate.
Complications Two pediatricians reviewed clinical criteria from each patient and defined and agreed on the definitions of complications and designation of major and minor. The list of 35 complications identified for the study infants is shown in Table I. These include respiratory, infectious, cardiovascular, electrolyte, and other complications. Specific treatments (eg, cardiopulmonary resuscitation [CPR] or intubation), diagnosis codes, laboratory tests, radiographic findings, culture results, vital signs, or signs, symptoms, or physical findings were used to define each complication. Major complications included respiratory failure, apneic episodes, pneumothorax, sepsis, hypotension/shock, CPR, and seizures.
Statistical Analysis Descriptive statistics (mean, standard deviation, median, percent) were used to describe study variables by various categories. Patient (age in months) and outcome variables (hospital and PICU LOS and costs) for infants with and without specified types of risk factors and specified complications were compared by means of v2 tests for discrete data and nonparametric Wilcoxon tests (for 2-sample comparisons) or Kruskal-Wallis analysis of variance tests (for $3-sample comparisons) for continuous data to account for possible nonnormal distributions of LOS and cost. In addition, multivariate models that included demographics, risk factors, individual respiratory complications, and classes of other complications (cardiac, infectious, electrolyte, and other) were built to determine independent associations between complications and LOS and costs. Prematurity was defined by four GA groups: #32 weeks, 33 to 35 weeks, 36 weeks, and $37 weeks, based on data recorded in the medical record and missing for infants without data. Sensitivity analyses were performed by either varying the definitions of the premature infant groupings (grouping 32 weeks GA infants with 33 to 35 weeks GA infants) or comparing findings for RSV+ versus not tested and RSV-infants.
RESULTS Demographics The study sample consisted of 684 infants #1 year of age who were hospitalized for bronchiolitis or RSV pneumonia as a principal (n = 612) or secondary (n = 72) diagnosis over an 18-month study period in 10 children’s medical centers. RSV was the most common causative agent, identified S143
Table I. Complications in 684 infants with bronchiolitis or RSV pneumonia Complication Respiratory Respiratory failure Apneic episodes Stridor Hemoptysis Infiltrates/atelectasis Hyperinflation Pneumothorax Pleural effusion Infectious Otitis media Bacterial pneumonia Aspiration pneumonia Sepsis/bacteremia UTI Meningitis (S pneumoniae) Diarrhea (5 due to rotavirus) Thrush/diaper rash Cardiovascular Hypotension/inotrope use/shock Cardiac arrhythmias Cardiopulmonary resuscitation Electrolyte Hyponatremia (Na+ <130) Hypokalemia (K+ <3.5) Hyperkalemia (K+ >6.0) Hypocalcemia (Ca2+ <8.0) Hypercalcemia (Ca2+ >11) Hypoglycemia (glucose <40) Hyperglycemia (glucose >200) Metabolic acidosis (HCO3 <16) Metabolic alkalosis (HCO3 >30) Other Adverse drug reaction Anemia Seizure Coagulopathy Vocal cord injury GI bleeding Hyperbilirubinemia
No. of patients
Percent
96 60 9 1 293 142 4 3
14.0 8.8 1.3 0.2 42.8 20.8 0.6 0.4
173 52 1 40 8 1 14 49
25.3 7.6 0.2 5.9 1.2 0.2 2.1 7.2
37 17 6
5.4 2.5 0.9
4 45 69 9 1 2 17 14 32
0.6 6.6 10.1 1.3 0.2 0.3 2.5 2.1 4.7
6 41 12 4 1 1 10
0.9 6.0 1.8 0.6 0.2 0.2 1.5
with 83% of 505 children tested having a positive test for RSV (26% were not tested). The average age was 3.4 ± 3.2 months, and 58% were male.
Outcomes Outcomes were generally good. The overwhelming majority of infants (98%) were discharged to home, and there was only 1 death. This child had coarctation of the aorta, presented with shock, and failed to recover despite extracorS144 Willson et al
poreal membrane oxygenation (ECMO). Two children were discharged to skilled nursing care facilities, although both appeared to be recovering without sequelae. Four children were transferred to other institutions before discharge, 2 after a hospitalization of <48 hours. Eight children were discharged with home health care. About one third (31%) of children were admitted to intensive care. The average hospital LOS was 5.0 ± 5.5 days; average PICU LOS was 5.2 ± 6.7 days; and average hospital costs were $9063 ± $13,220 (adjusted to year 2000 dollars).
Complications: Frequency and Bivariate Associations with LOS and Costs Despite the generally good outcomes, complications were common. We defined 35 complications for the purpose of this study (Table I). The majority of infants (n = 543, 79.4%) had 1 or more complications: 218 infants had one complication, 152 had two complications, and 173 had 3 to 11 complications. Most complications were not serious (n = 379, 55.4% had only minor complications), but overall the presence of complications was significantly associated with longer hospital and PICU LOS and higher costs (Table II). Infants with minor complications only had on average 1 day longer hospital LOS (P < .0001), 0.8 days longer PICU LOS (P = .016), and $1650 higher cost (P = .001) compared with infants with no complications. Infants with major complications (n = 164, 24%) had on average 7.3 days longer hospital LOS, 6.5 days longer PICU LOS, and $18,650 higher cost (P < .0001) compared with infants with no complications. As would be expected, respiratory complications were the most frequent, and the presence of any respiratory complication was significantly associated with an increase in hospital costs and LOS (P < .0001) (Table II). Infants with respiratory complications only (n = 146) and infants with both respiratory and nonrespiratory complications (n = 264) had significantly longer hospital and PICU LOS and cost significantly more than infants with no complications (P # .003). Infants with nonrespiratory complications only (n = 133) had significantly longer hospital and PICU LOS (P # .005) but not significantly higher costs (P = .65) compared with infants with no complications. Overall, 96 (14%) infants required mechanical ventilation either for apnea or respiratory failure. These infants were generally younger than those with no complications (1.6 vs 3.7 months, respectively, P < .0001; Table II). Mechanical ventilation was significantly more likely to occur in premature infants (28.7%), those with CHD (31.7%), or those with other congenital abnormalities (37.3%) than in infants with no risk factors (9.1%; P < .0001). The development of respiratory failure was associated with a 5-times increase in LOS and a 9-times increase in hospital costs. Apnea, the presence of radiographic infiltrates/atelectasis, and hyperinflation on radiography were also associated with significant increases in LOS and costs (P < .0003). Stridor was reported in 9 children; 5 in association with mechanical ventilation. Pneumothorax was seen in 4 (0.6%) and pleural effusions in 3 (0.4%) patients. The Journal of Pediatrics November 2003
Table II. Association of complications with hospital resource use Complication
Hospital LOS
PICU LOS
Costs
Age (mo)
3484 ± 2169 (3078) 10,399 ± 14,364 (4899) P < .0001 6293 ± 6273 (4095) P < .0001 4217 ± 4639 (3013) P = .65 15,640 ± 18,229 (8962) P < .0001
3.7 ± 3.1 (3.0) 3.4 ± 3.2 (2.0) P = .05 2.8 ± 2.9 (2.0) P = .002 4.4 ± 3.6 (4.0) P = .24 3.2 ± 3.1 (2.0) P = .02
12,367 ± 15,789 (6,475) P < .0001 31,481 ± 21,382 (25,909) P < .0001 20,242 ± 20,745 (12,824) P < .0001 14,453 ± 17,080 (7686) P < .0001 9205 ± 11,849 (4728) P < .0001 9012 ± 15,431 (4182) P < .0001 6274 ± 11,422 (3496) P = .02 9455 ± 12,296 (5474) P < .0001 26,410 ± 31,704 (14,726) P < .0001 27,149 ± 23,238 (20,445) P < .0001 28,699 ± 24,847 (26,003) P < .0001 20,610 ± 15,302 (20,167) P < .0001 24,700 ± 22,841 (18,714) P < .0001 20,667 ± 12,510 (18,609) P < .0001 25,348 ± 27,029 (14,104) P < .0001 24,872 ± 29,274 (14,094) P < .0001
3.0 ± 3.1 (2.0) P = .003 1.6 ± 1.9 (1.0) P < .0001 1.8 ± 2.3 (1.0) P < .0001 2.9 ± 3.0 (2.0) P = .001 3.4 ± 3.3 (2.0) P = .17 4.2 ± 3.5 (3.0) P = .27 5.1 ± 3.6 (4.0) P = .002 4.4 ± 3.5 (4.0) P = .33 1.9 ± 1.7 (1.5) P = .0007 2.3 ± 2.4 (1.0) P = .001 2.6 ± 2.7 (2.0) P = .04 1.8 ± 2.1 (1.0) P = .006 2.4 ± 2.5 (2.0) P < .0001 1.8 ± 1.5 (1.0) P = .03 2.4 ± 2.7 (2.0) P = .001 2.8 ± 2.6 (2.0) P = .06
Mutually exclusive groups No complications Any complication
n = 141 n = 543
Respiratory complications only Non-respiratory complications only Both respiratory and nonrespiratory complications
n = 146 n = 133 n = 264
2.7 ± 1.5 (2.0) 5.6 ± 5.9 (4.0) P < .0001 3.9 ± 2.8 (3.0) P < .0001 3.2 ± 1.8 (3.0) P = .003 7.7 ± 7.6 (5.0) P < .0001
1.1 ± 0.9 (0.8) 5.6 ± 6.9 (3.7) P < .0001 3.0 ± 2.9 (1.9) P = .003 2.0 ± 1.0 (2.2) P = .005 6.9 ± 7.8 (4.8) P < .0001
Non–mutually exclusive groups Any respiratory complication Respiratory failure
n = 410 n = 96
Apnea n = 60 Atelectasis/infiltrates n = 293 Hyperinflation n = 142 Any infectious complication n = 280 Otitis media n = 173 Bacterial pneumonia n = 52 Sepsis/bacteremia n = 40 Any cardiovascular complication Hypotension and/or inotrope Cardiac arrhythmias
n = 61 n = 37 n = 17
Any electrolyte complication Metabolic acidosis
n = 132 n = 14
Other complications n = 64 Anemia n = 41
6.3 ± 6.6 (4.0) P < .0001 13.5 ± 9.6 (11.0) P < .0001 9.8 ± 8.5 (7.5) P < .0001 7.1 ± 6.9 (5.0) P < .0001 5.0 ± 4.6 (4.0) P < .0001 5.3 ± 6.8 (3.0) P < .0001 4.1 ± 5.3 (3.0) P < .0001 5.7 ± 6.1 (3.5) P < .0001 12.2 ± 13.8 (7.0) P < .0001 11.6 ± 10.3 (9.0) P < .0001 10.8 ± 10.8 (8.0) P < .0001 10.5 ± 7.9 (9.0) P < .0001 10.3 ± 9.5 (8.0) P < .0001 10.1 ± 5.8 (9.5) P < .0001 10.8 ± 11.5 (7.5) P < .0001 10.1 ± 11.6 (7.0) P < .0001
6.0 ± 7.1 (3.9) P < .0001 9.0 ± 8.2 (6.9) P < .0001 7.5 ± 7.1 (4.9) P < .0001 6.4 ± 6.8 (4.5) P < .0001 4.3 ± 4.4 (2.9) P = .0003 6.4 ± 9.8 (3.0) P < .0001 4.3 ± 9.1 (1.9) P = .007 4.9 ± 6.3 (1.8) P = .009 11.4 ± 13.9 (5.1) P < .0001 8.9 ± 8.7 (7.0) P < .0001 8.2 ± 9.2 (7.0) P < .0001 7.5 ± 5.8 (6.9) P < .0001 8.6 ± 8.9 (6.6) P < .0001 7.1 ± 4.8 (6.4) P < .0001 9.3 ± 11.1 (6.5) P < .0001 9.6 ± 11.4 (6.5) P < .0001
For hospital LOS (days), PICU LOS (days), costs ($), and age in months, table values are mean ± SD (median). The means in each row are compared with the no complications group, using nonparametric 2-sample Wilcoxon tests.
Overall, only 15% of the radiographs taken were interpreted as normal. Infectious complications were the second most common (40.9%) and as a group were associated with significant increases in LOS and costs (P < .0001) (Table II). Otitis Complications in Infants Hospitalized for Bronchiolitis or Respiratory Syncytial Virus Pneumonia
media was diagnosed in 173 (25.3%), most often in children without risk factors (28.3% vs #18.4% in infants with risk factors, P # .07) and was significantly associated with increased LOS and costs (P # .02). Bacterial pneumonia, as evidenced by either a secondary ICD-9 code or stated rationale S145
for use of antibiotics, was identified in 52 (7.6%) infants. An ICD-9 code for sepsis/bacteremia was present in 40 (5.9%) patients, although only 14 positive blood cultures were reported, 10 of which were coagulase-negative staphylococcus. These infants were younger than those with no complications (1.9 vs 3.7 months, P = .0007) and were more likely than infants without sepsis to have a congenital abnormality (22.5% vs 7.8%; P = .001), to be on mechanical ventilation (47.5% vs 12%; P < .0001), and to have indwelling arterial or central venous catheters (27.5% vs 6.8%; P < .0001). The diagnoses of either bacterial pneumonia or sepsis were associated with significantly greater costs and LOS (P < .009). Eight infants carried the diagnosis of urinary tract infection (UTI), although only 3 positive urine cultures were documented. Meningitis (S pneumoniae) was identified in one 9-month-old infant. Gastroenteritis or diarrhea developed in 14 infants, 5 of whom had rotavirus identified. Thrush or diaper rash was diagnosed in 49 (7.2%) infants. Antibiotics were used in 465 (68%) of all infants. Electrolyte disturbances were common. Although these are in general considered to be of little consequence, as a group they were associated with more than a 3-times increase in LOS and 7-times increase in costs (Table II). Hypokalemia (K+ < 3.5) was noted in 45 (6.6%) patients and metabolic alkalosis (HCO3 >30) in 32 (4.7%) patients. Both hypokalemia and metabolic alkalosis were strongly correlated with use of furosemide (P < .0001). Hyperkalemia was also common (n = 69, 10%). We suspect much of this might be related to difficulty with blood sampling in small infants (with the likelihood that many samples were obtained by ‘‘heel stick’’). Hyponatremia was reported in 4 infants, hypocalcemia in 9, and hypercalcemia in 1. Hypoglycemia ( < 40) was noted in 2 infants; hyperglycemia (>200) was reported in 17. Fourteen children had significant metabolic acidosis defined as HCO3 < 16. Two of these children also required CPR, 3 received inotropes, and 8 had respiratory failure and were on mechanical ventilation. Cardiac dysfunction is not generally thought to be a common feature of bronchiolitis or RSV, but the ICD-9 code for shock was reported in 5 infants, and 35 infants were treated with inotropes during their hospital stay. Arrhythmias were described in 17 children, but most were PVCs or PACs. Two children had ventricular tachycardia. Cardiovascular complications were significantly more common in infants with CHD (51.2%) and in infants with other congenital anomalies (22.0%) than in infants with no risk factors (5.4%) (P < .0001). Six children required CPR. Two of these children had underlying cardiac defects (both coarctation of the aorta), two had airway anomalies, and one was septic. In all cases, CPR was associated with respiratory failure and the need for ventilatory support. One child died, but the others were successfully resuscitated. Miscellaneous complications included anemia, seizures, adverse drug reactions, frank hemoptysis, hyperbilirubinemia, vocal cord injury, and GI hemorrhage. Anemia, defined by hematocrit <25% or hemoglobin <8, occurred in 41 (6.0%) patients. These children were borderline younger (P = .06), but they were not more likely to be premature than patients without S146 Willson et al
anemia (P = .39) or without risk factors (P = .20). Although anemia was significantly associated with the presence of an arterial and/or central venous catheter (P < .0001), still, 61% of infants with anemia did not have a line. Anemia was associated with a longer LOS (10.1 vs 2.7 days; P < .0001) and more than a 7-times increase in hospital costs ($24,872 vs $3484, Table II). Twelve infants carried a diagnosis of seizures and manifested seizures during their hospitalization; one had an episode of status. Six adverse drug reactions were reported but were not further characterized in the records. The child with hemoptysis mentioned above was the single patient who died. Before death, this child had multiple problems including respiratory failure, infection, coagulopathy, and treatment with ECMO. Among the 10 children with hyperbilirubinemia, 4 were considered to have physiologic jaundice, 1 Rh incompatibility, 3 were related to sepsis, and 2 were mild and present on admission. The cause of vocal cord injury in one child was unclear. There was only one instance of GI hemorrhage.
Risk Factors Although the majority (n = 516, 75.4%) of the infants had no significant health problems (significant risk factors), 87 (12.7%) were former premature infants (#35 weeks GA), 41 (6.0%) had CHD, and 59 (8.6%) had other congenital problems ranging from metabolic abnormalities to cleft palate (Table III). Infants with congenital abnormalities other than CHD tended to be older (average age, 4.5 vs 3.4 months, respectively, P = .04), but the risk factor groups otherwise did not differ demographically. The frequency of complications, LOS, and costs tended to be significantly higher for infants with risk factors (Table III) compared with infants with no risk factors recorded. Infants with risk factors were significantly more likely to have respiratory complications (71.3%-81.4%) than those with no risk factors (55.8%) (P # .03). Also, infants with risk factors were significantly more likely to have electrolyte complications (31.0%-39.0%) than those with no risk factors (14.9%) (P # .0006). Infectious complications were less common in children with CHD than in children without risk factors (22.0% vs 42.8%; P = .008). Degree of prematurity was significantly associated with complications. Former preterm infants of 33 to 35 weeks GA had the highest rates of complications (93.0%), longest hospital LOS (7.4 days), and highest costs ($14,137) (Table IV). There were significant differences in the age at hospital admission among the GA groups, and the 33 to 35 GA infants were the youngest (2.7 vs >3.0 months for other groups; P < .0001). When we deleted the 32 weeks GA infants from the #32 weeks GA group and combined them with the 33 to 35 weeks GA infants, the previous significant differences shown in Table IV in complication rates, hospital LOS, and costs were fundamentally similar, with the 32 to 35 weeks GA group having the highest rates of complications, longest average hospital LOS, and highest average costs. When the same analyses were performed on the RSV+ subsample (n = 417 infants), all the same patterns of hospital resource use and complications remained. The Journal of Pediatrics November 2003
Table III. Association of risk factors with complications and hospital resource use Risk group No risk factors Congenital heart disease Other congenital abnormalities Premature
% Complications
Hospital LOS
PICU LOS
Costs
76.5% 92.7% P = .02 89.8% P = .02 87.4% P = .02
4.0 ± 3.9 (3.0) 7.7 ± 5.9 (6.0) P < .0001 10.7 ± 10.9 (8.0) P < .0001 6.7 ± 5.8 (4.0) P < .0001
4.2 ± 5.2 (2.5) 5.1 ± 3.4 (4.1) P = .03 9.1 ± 11.9 (5.8) P = .002 5.7 ± 5.0 (4.6) P = .038
6823 ± 9924 (3777) 16,644 ± 15,308 (11,335) P < .0001 21,426 ± 25,296 (13,241) P < .0001 12,634 ± 12,952 (7376) P < .0001
n = 516 n = 41 n = 59 n = 87
For hospital LOS (days), PICU LOS (days), costs ($), and age in months, table values are mean ± SD (median). The means in each row are compared with the no risk factors group, using nonparametric 2-sample Wilcoxon tests. The percentages in the comorbidity groups are compared with the no risk factors group, using Fisher exact tests.
Table IV. Association of GA with complications and hospital resource use
Any complications Hospital LOS PICU LOS Cost Age in mo
n = 543
#32 wk GA n = 44
33–35 wk GA n = 43
36 wk GA n = 46
$37 wk GA n = 338
GA missing n = 213
81.8% (36) 6.1 ± 5.1 (4.0) 4.7 ± 4.5 (3.9) 11,015 ± 9752 (7339) 3.8 ± 3.1 (3.0)
93.0% (40) 7.4 ± 6.5 (5.0) 6.7 ± 5.4 (5.0) 14,137 ± 5309 (8129) 2.7 ± 2.5 (2.0)
82.6% (38) 6.0 ± 8.0 (3.5) 8.4 ± 9.7 (4.5) 11,118 ± 18,504 (5741) 3.0 ± 3.2 (1.5)
81.7% (276) 4.5 ± 4.6 (3.0) 4.4 ± 6.4 (2.5) 8055 ± 12,007 (3903) 3.1 ± 3.2 (2.0)
71.8% (153) 4.8 ± 5.7 (3.0) 5.3 ± 7.3 (3.1) 8716 ± 13,646 (4055) 4.2 ± 3.3 (3.0)
P value P = .008* P = .004y P = .045y P = .002y P < .0001y
For the first row, table values are percent (number of infants). For hospital LOS (days), PICU LOS (days), costs ($), and age in months, table values are mean ± SD (median). *The P value is from a v2 test of a 5 3 2 contingency table. yMeans compared by nonparametric Kruskal-Wallis tests.
Multivariate Associations Between Complications, Risk factors, LOS, and Costs Linear regression controlling for age, sex, and risk factors confirmed the importance of both respiratory and nonrespiratory complications as predictors of increased LOS and costs. Individual respiratory complications of respiratory failure, atelectasis, pneumothorax, stridor, apnea, and hyperinflation were independently entered into the model, and each (with the exception of apnea) independently predicted increases in LOS and costs. To simplify model-building, nonrespiratory complications were entered into the model in groups, including cardiovascular, infectious, electrolyte, and other. Each of these groups of complications independently predicted increases in LOS and costs. In addition, having a noncardiac congenital abnormality predicted increases in LOS and costs. Altogether, the resulting models explained R2 = 64% of the variation in LOS and R2 = 73% of the variation in cost for patients admitted with VLRI infections.
DISCUSSION Complications were common in infants hospitalized for bronchiolitis or RSV and occurred disproportionately in infants with underlying congenital abnormalities or preComplications in Infants Hospitalized for Bronchiolitis or Respiratory Syncytial Virus Pneumonia
maturity. Although many could be considered minor, even minor complications and complications as common as electrolyte imbalance were associated with significant increases in hospital LOS and costs. Serious complications affected 24% of the infants and were associated with large and highly significant increases in hospital resource use. Respiratory complications were the most common and among the most serious. They were more frequent in former preterm infants, not surprising, given their smaller size and proportionately smaller airways. The greater risk of respiratory complications also extended to children with congenital abnormalities, but the variety of diagnoses precluded identifying a single unifying cause. The development of respiratory failure and consequent need for respiratory support greatly escalates the use of other supportive measures (eg, sedation, monitoring lines, and laboratory measurements). It is therefore not surprising that respiratory complications were associated with longer LOS and higher average hospital costs. Although respiratory complications are anticipated as part of the underlying disease, the cardiovascular complications reported here are somewhat unexpected. There were many minor arrhythmias (eg, PACs and PVCs) but two cases of ventricular tachycardia. One was clearly associated with administration of nebulized albuterol (and stopped when the S147
drug was stopped) and the other was a child with coarctation of the aorta who had undergone cardiac repair at that hospitalization. Other cardiovascular complications such as shock, use of inotropic support, or need for CPR are also not generally thought to accompany VLRI. The majority of infants in this study were infected with RSV, and RSV is not known to spread beyond the respiratory tract (eg, there is no viremic phase of infection).10 Although case reports of ventricular dysrhythmias and cardiogenic shock with RSV infection have been published,11,12 there is little evidence that RSV infection causes myocarditis or primary cardiac dysfunction. Most (57%) of the patients with shock/inotrope use were on positive-pressure ventilation, 13 had some form of CHD, and 5 had the complication of sepsis. Thus, relative hypovolemia in the face of positive-pressure ventilation or secondary myocardial dysfunction from CHD or sepsis would seem more likely explanations for hypotension or need for inotropic support than primary myocardial dysfunction from RSV infection. Additionally, since half of the inotrope use was in a single institution, physician preference might also have played a role. Infectious complications were also common but probably were overdiagnosed. Otitis media is well described in VLRI but may not always represent bacterial superinfection.13,14 Similarly, the diagnosis of bacterial pneumonia in the face of bronchiolitis or RSV infection is extremely difficult. Fever, pulmonary infiltrates, positive tracheal aspirate cultures, and elevated WBCs are common, and their presence does not distinguish bacterial from viral causation. The infectious complication of most concern was sepsis or bacteremia, because this was associated with more than a 4-times increase in LOS and more than 7-times increase in costs. Forty patients were identified with sepsis or bacteremia, although only 14 positive blood cultures were reported (10 were coagulasenegative staphylococcus). Although a positive blood culture is not required to make the diagnosis of sepsis, it is not clear from the records how this diagnosis was made. Other investigators have found a much lower incidence of bacterial complications in VLRI.15,16 The use of broad-spectrum antibiotics in 68% of these patients undoubtedly reflects the frequency with which these infectious complications were suspected and the fragile nature of the population being cared for. The electrolyte complications are probably of little consequence from a morbidity perspective but bear mentioning because they are common and because they are associated with increased costs and LOS. Most could legitimately be considered minor. Both hypokalemia and metabolic alkalosis were strongly associated with use of furosemide. The high incidence of hyperkalemia is unexplained but probably represents the practice of collecting blood by heel stick in small infants. Hypoglycemia was rare but hyperglycemia common and probably related to steroid administration. Hyperbilirubinemia was also common but of little consequence and, in most cases, physiologic. The occurrence of metabolic acidosis is probably more concerning but was frequently associated with other problems, including sepsis and dehydration. Most of these children were relatively sick, as evidenced by the fact that the majority was on ventilators and S148 Willson et al
several required CPR and/or inotropic medications. In 6 of 14, however, metabolic acidosis was associated with nothing more than transient hypokalemia or hyperkalemia. Among the miscellaneous complications, the most common was anemia (n = 41, 6.0%). Surprisingly, these infants were not more likely to be premature or younger in age. They were, however, more likely to be in the PICU, intubated, and have indwelling invasive catheters. It is likely, therefore, that anemia in many cases was a consequence of frequent blood draws and invasive procedures. Other miscellaneous complications, including seizures, coagulopathy, hyperbilirubinemia, and hemoptysis, were either rare or of little consequence. Only 6 adverse drug reactions were reported, but prior studies have demonstrated substantial underreporting of adverse drug events.17,18 The low frequency of GI hemorrhage merits comment just because it is so low given that nearly one third of these patients were intensive care patients. The low incidence of GI hemorrhage in infants has been commented upon by other investigators.19 The association of particular complications with specific risk factors is not unanticipated but may help identify infants at risk. One surprise from our analysis, however, is the longer hospital LOS and higher costs in 33 to 35 weeks GA premature infants relative to infants born at earlier GA. This finding has not been reported previously. The higher incidence of complications and younger average age may have been important determinants of the higher LOS and costs. Age at admission has been reported previously as a risk factor for severe disease.7,20 The PICNIC study also found that infants 33 to 35 weeks GA were just as much at risk for RSV infection as infants #32 weeks GA as the result of both their prematurity and younger age at admission.20 These infants appear to have been exposed to RSV at an earlier age, possible due to more rapid discharge from the hospital or less rigorous precautions to environmental exposure. Such exposure at an earlier age leads to increased risk of severe RSV illness comparable to the risk in more premature groups. The outcome of infants with VLRI is generally good, but complications are common. The type of complication(s) is influenced by comorbid conditions; complications, even minor ones, have significant impact on resource utilization. Hospital costs to care for this group of infants approach 1 billion dollars per year in the United States. In addition to these immediate costs, rates of rehospitalization in the year after discharge exceed 20% in some studies, with >40% of infants having subsequent development of asthma.21-24 Given the high rate of complications and the possibility of long-term disability associated with bronchiolitis or RSV pneumonia, either more effective acute therapy is needed or more liberal use of preventive strategies should be considered in the high-risk groups identified in this study.
CONCLUSIONS Bronchiolitis and RSV pneumonia in infants is generally a self-limited disease, but infants ill enough to require hospitalization may have significant complications. Complications The Journal of Pediatrics November 2003
are more common in infants with preexisting medical problems and are associated with longer LOS and higher costs. It may be reasonable to consider broader use of preventive strategies in these higher-risk infants.
COMMENTS FROM THE AUDIENCE John V. Williams, MD, Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee: RSV doesn’t cause anemia. Children may have or become anemic, but RSV does not cause it.
Douglas F. Willson, MD, Associate Professor of Pediatrics and Director, Pediatric Intensive Care Unit, Children’s Medical Center, University of Virginia Health System, Charlottesville, Virginia: If an infant is hospitalized in the ICU for RSV, it is almost guaranteed that a central line is put in and the child will become anemic over time. So anemia is not directly a complication of RSV but a complication of the therapy or hospitalization for RSV or bronchiolitis.
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