Recovery Trajectories in Children Requiring 3 or More Days of Invasive Ventilation.

OBJECTIVES: To characterize health-related quality of life (HRQL) and functional recovery trajectories and risk factors for prolonged impairments among critically ill children receiving greater than or equal to 3 days of invasive ventilation. DESIGN: Prospective cohort study. SETTING: Quaternary children's hospital PICU. PATIENTS: Children without a preexisting tracheostomy who received greater than or equal to 3 days of invasive ventilation, survived hospitalization, and completed greater than or equal to 1 postdischarge data collection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated 144 children measuring HRQL using proxy-report Pediatric Quality of Life Inventory and functional status using the Functional Status Scale (FSS) reflecting preillness baseline, PICU and hospital discharge, and 1, 3, 6, and 12 months after hospital discharge. They had a median age of 5.3 years (interquartile range, 1.1-13.0 yr), 58 (40%) were female, 45 (31%) had a complex chronic condition, and 110 (76%) had normal preillness FSS scores. Respiratory failure etiologies included lung disease ( n = 49; 34%), neurologic failure ( n = 23; 16%), and septic shock ( n = 22; 15%). At 1-month postdischarge, 68 of 122 (56%) reported worsened HRQL and 35 (29%) had a new functional impairment compared with preillness baseline. This improved at 3 months to 54 (46%) and 24 (20%), respectively, and remained stable through the remaining 9 months of follow-up. We used interaction forests to evaluate relative variable importance including pairwise interactions and found that therapy consultation within 3 days of intubation was associated with better HRQL recovery in older patients and those with better preillness physical HRQL. During the postdischarge year, 76 patients (53%) had an emergency department visit or hospitalization, and 62 (43%) newly received physical, occupational, or speech therapy. CONCLUSIONS: Impairments in HRQL and functional status as well as health resource use were common among children with acute respiratory failure. Early therapy consultation was a modifiable characteristic associated with shorter duration of worsened HRQL in older patients.

Endothelial Glycocalyx Degradation Patterns in Sepsis-Associated Pediatric Acute Respiratory Distress Syndrome: A Single Center Retrospective Observational Study.

BACKGROUND: Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of acute respiratory distress syndrome (ARDS). Constituents of the EGCX shed into circulation, glycosaminoglycans and proteoglycans, may serve as biomarkers of endothelial dysfunction. We sought to define the patterns of plasma EGCX degradation products in children with sepsis-associated pediatric ARDS (PARDS), and test their association with clinical outcomes. METHODS: We retrospectively analyzed a prospective cohort (2018-2020) of children (≥1 month to <18 years of age) receiving invasive mechanical ventilation for acute respiratory failure for ≥72 h. Children with and without sepsis-associated PARDS were selected from the parent cohort and compared. Blood was collected at time of enrollment. Plasma glycosaminoglycan disaccharide class (heparan sulfate, chondroitin sulfate, and hyaluronan) and sulfation subtypes (heparan sulfate and chondroitin sulfate) were quantified using liquid chromatography tandem mass spectrometry. Plasma proteoglycans (syndecan-1) were measured through an immunoassay. RESULTS: Among the 39 mechanically ventilated children (29 with and 10 without sepsis-associated PARDS), sepsis-associated PARDS patients demonstrated higher levels of heparan sulfate (median 639 ng/mL [interquartile range, IQR 421-902] vs 311 [IQR 228-461]) and syndecan-1 (median 146 ng/mL [IQR 32-315] vs 8 [IQR 8-50]), both p = 0.01. Heparan sulfate subtype analysis demonstrated greater proportions of N-sulfated disaccharide levels among children with sepsis-associated PARDS (p = 0.01). Increasing N-sulfated disaccharide levels by quartile were associated with severe PARDS (n = 9/29) with the highest quartile including >60% of the severe PARDS patients (test for trend, p = 0.04). Higher total heparan sulfate and N-sulfated disaccharide levels were independently associated with fewer 28-day ventilator-free days in children with sepsis-associated PARDS (all p < 0.05). CONCLUSIONS: Children with sepsis-associated PARDS exhibited higher plasma levels of heparan sulfate disaccharides and syndecan-1, suggesting that EGCX degradation biomarkers may provide insights into endothelial dysfunction and PARDS pathobiology.

Development and Prospective Validation of Tools to Accurately Identify Neurosurgical and Critical Care Events in Children With Traumatic Brain Injury.

OBJECTIVE: To develop and validate case definitions (computable phenotypes) to accurately identify neurosurgical and critical care events in children with traumatic brain injury. DESIGN: Prospective observational cohort study, May 2013 to September 2015. SETTING: Two large U.S. children's hospitals with level 1 Pediatric Trauma Centers. PATIENTS: One hundred seventy-four children less than 18 years old admitted to an ICU after traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Prospective data were linked to database codes for each patient. The outcomes were prospectively identified acute traumatic brain injury, intracranial pressure monitor placement, craniotomy or craniectomy, vascular catheter placement, invasive mechanical ventilation, and new gastrostomy tube or tracheostomy placement. Candidate predictors were database codes present in administrative, billing, or trauma registry data. For each clinical event, we developed and validated penalized regression and Boolean classifiers (models to identify clinical events that take database codes as predictors). We externally validated the best model for each clinical event. The primary model performance measure was accuracy, the percent of test patients correctly classified. The cohort included 174 children who required ICU admission after traumatic brain injury. Simple Boolean classifiers were greater than or equal to 94% accurate for seven of nine clinical diagnoses and events. For central venous catheter placement, no classifier achieved 90% accuracy. Classifier accuracy was dependent on available data fields. Five of nine classifiers were acceptably accurate using only administrative data but three required trauma registry fields and two required billing data. CONCLUSIONS: In children with traumatic brain injury, computable phenotypes based on simple Boolean classifiers were highly accurate for most neurosurgical and critical care diagnoses and events. The computable phenotypes we developed and validated can be used in any observational study of children with traumatic brain injury and can reasonably be applied in studies of these interventions in other patient populations.

Functional Status Scale in Children With Traumatic Brain Injury: A Prospective Cohort Study.

OBJECTIVES: In children with traumatic brain injury, 1) to describe the hospital discharge functional outcome and change from baseline function using the Functional Status Scale and 2) to determine any associations between discharge Functional Status Scale and age, injury mechanism, neurologic examination, imaging, and other predictors of outcome. DESIGN: Prospective observational cohort study, May 2013 to November 2015. SETTING: Two U.S. children's hospitals designated as American College of Surgeons level 1 pediatric trauma centers. PATIENTS: Children less than 18 years old admitted to an ICU with acute traumatic brain injury and either a surgical or critical care intervention within the first 24 hours or in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital discharge Functional Status Scale. Most, 133 of 196 (68%), had severe traumatic brain injury (admission Glasgow Coma Scale, 3-8). Overall hospital mortality was 14%; 20% among those with severe traumatic brain injury. Hospital discharge Functional Status Scale had an inverse relationship with Glasgow Coma Scale: for each increase in admission Glasgow Coma Scale by 1, the discharge Functional Status Scale decreased by 0.5 (95% CI, 0.7-0.3). Baseline Functional Status Scale was collected at one site (n = 75). At that site, nearly all (61/62) of the survivors had normal or near-normal (≤ 7) preinjury Functional Status Scale. More than one-third, 23 of 62 (37%), of survivors had new morbidity at hospital discharge (increase in Functional Status Scale, ≥ 3). Among children with severe traumatic brain injury who had baseline Functional Status Scale collected, 21 of 41 survivors (51%) had new morbidity at hospital discharge. The mean change in Functional Status Scale from baseline to hospital discharge was 3.9 ± 4.9 overall and 5.2 ± 5.4 in children with severe traumatic brain injury. CONCLUSIONS: More than one-third of survivors, and approximately half of survivors with severe traumatic brain injury, will have new morbidity. Hospital discharge Functional Status Scale, change from baseline Functional Status Scale, and new morbidity acquisition can be used as outcome measures for hospital-based care process improvement initiatives and interventional studies of children with traumatic brain injury.

Molecular analysis of endotracheal tube biofilms and tracheal aspirates in the pediatric intensive care unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a known complication of mechanically ventilated children in the pediatric intensive care unit (PICU). Endotracheal tube (ETT) biofilms are often implicated in the development of VAP by providing a conduit for pathogens to the lower respiratory tract. METHODS: A prospective cohort study from April 2010-March 2011 of children 4 weeks to 18 years of age ventilated for greater than 72 hours to determine the microbiota of ETT biofilms and tracheal aspirates. RESULTS: Thirty-three patients were included with a mean age of 6.1 years (SD ± 5.1 years) and average length of intubation of 8.8 days (SD ± 5.0 days). Bacterial communities from tracheal aspirates and the proximal and distal ends of ETTs were determined using 16S rRNA gene libraries. Statistical analysis utilized two-part statistics and the Wilcoxon signed rank sum test for comparison of bacterial communities. Sequencing revealed a predominance of oropharyngeal microbiota including Prevotella and Streptococcus spp. Pathogenic bacterial genera including Staphylococcus, Burkholderia, Moraxella, and Haemophilus were also represented. Bacterial load was greatest at the proximal aspect of the ETT. Duration of intubation did not significantly impact bacterial load. Morisita Horn analysis across sites showed similar communities in 24/33 (72%) of patients. CONCLUSIONS: ETT biofilms and tracheal aspirates of intubated patients in the PICU primarily consisted of oropharyngeal microbiota, but had a significant representation of potentially pathogenic genera. While the majority of patients had similar microbiota when comparing their ETT biofilms and tracheal aspirates, a subset of patients showed a divergence between communities that requires further investigation.