BACKGROUND:Pediatric traumatic brain injury (pTBI) often leads to cognitive, behavioral, and motor impairments. NLRP3 inflammasome proteins, such as ASC and caspase-1, may serve as biomarkers for TBI severity due to their role in neuroinflammation. This study aims to assess the association between serum ASC and caspase-1 levels and TBI severity in pediatric patients. METHODS:Serum samples were collected at pediatric intensive care unit (ICU) admission (first post-admission), and at 24 and 48 h post-admission, from TBI participants aged 28 days to 18 years and from demographically matched controls. TBI severity was assessed using the Glasgow Coma Scale (GCS). RESULTS:We analyzed samples from 77 pTBI patients and 31 controls. ASC levels were significantly higher across all GCS categories, with the most pronounced differences in the severe category at first post-admission (p = 0.0005, AUROC 0.83) and 24 h post-admission (p < 0.0001, AUROC 0.83). Caspase-1 levels were significantly elevated in the severe category, particularly at first post-admission (p < 0.0001, AUROC 0.85). DISCUSSION:Elevated ASC and caspase-1 levels, especially in severe pTBI cases, suggest their potential as biomarkers for TBI severity. These findings emphasize the role of inflammasome proteins in post-TBI neuroinflammation and support further research into targeted therapies for pediatric TBI. IMPACT:Increased serum levels of inflammasome proteins ASC and caspase-1 in acute-phase post-admission samples are associated with severe TBI. To our knowledge, this is the first study to examine the inflammasome pathway in pediatric TBI patients across the severity spectrum using serum samples. The study enhances our understanding of NLRP3 inflammasome activation in pediatric TBI by profiling serum levels and examining their clinical correlation with injury severity. It suggests an adjunctive approach to the Glasgow Coma Scale with biomarkers for more precise TBI diagnosis. This research lays the groundwork for future therapeutic strategies targeting inflammasomes in pediatric TBI.

OBJECTIVES:In the PICU, predicting death within 1 hour after terminal extubation (TE) is valuable in augmenting family counseling and in identifying suitable candidates for organ donation after circulatory determination of death (DCDD). The objective of this study was to train and validate a machine learning model to predict death within 1 hour after TE. DESIGN:The Death One Hour After Terminal Extubation (DONATE) database was generated using multicenter retrospective data from 2009 to 2021. Data covering demographics, clinical features, vital signs, laboratory values, ventilator settings, medications, and procedures were collected. Machine learning models were trained to predict whether a pediatric patient would die within 1 hour after TE and evaluated on a holdout set. SETTING:Ten U.S. PICUs. PATIENTS:Children and adolescents, 0-21 years old, who died after TE ( n = 957). INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The final model was a parsimonious extra-trees model with 21 input features. It was trained on the 2009-2018 data from eight sites ( n = 634) and evaluated on a holdout set comprised of the 2019-2021 data of all ten sites ( n = 323), representing temporal and external validation. The area under the receiver operating characteristic curve and 95% CI was 0.84 (95% CI, 0.81-0.87). At a sensitivity of 90%, the positive predictive value (PPV) was 88%, the negative predictive value (NPV) was 70%, and the number needed to alert (NNA) was 1.14. Among potential organ donors, at the same sensitivity level, the PPV was 86%, the NPV was 74%, and the NNA was 1.17. CONCLUSIONS:Our model, trained and validated on multisite data, predicted whether a child will die within 1 hour of TE with high discrimination and a low false alarm rate. This finding has important applications to end-of-life counseling and institutional resource utilization when families wish to attempt DCDD.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

Cavazos, Joie1; Allen, Christine2; Avery, Leslie3; Baines, Torrey4; Brown, Ann-Marie5; Filipp, Stephanie6; Gee, Samantha7; Jacobs, Nekaiya8; Bloxham, Jodi9; Brothers, Elizabeth10; Elliott, Elizabeth11; Meghan Kendall, K.12; Koshel, Christine13; Lin, Ada14; Magner, Kristin15; Siruguppa, Krishna16; Wai, Kitman11; Pringle, Charlene17 Author Information

This retrospective, multicenter observational study analyzed data from 257 children under 2 years old admitted with viral bronchiolitis to pediatric intensive care units (PICU) at Wolfson Children’s Hospital and UFHealth Shands Children’s Hospital from January 2020 to March 2022. The study explores viral etiologies and their associations with hospital length of stay (H-LOS), PICU length of stay (P-LOS), and severity markers and scores. Younger age was associated with longer H-LOS and P-LOS ( P < .001). Respiratory syncytial virus (RSV) was associated with younger age but not with H-LOS when controlled for age. RSV’s impact on H-LOS varied by age ( P = .018). Markers of severity did not differ between patients infected with RSV versus those without RSV, or in patients with co-infection versus single infection. In our population, pSOFA performed better than PELOD-2 in disease severity assessment.

Introduction Propofol is a phenol agent with sedative and anesthetic properties that has been in use for decades, but with controversy in critically ill pediatric patients, given the concern for developing propofol-related infusion syndrome (PRIS). Our aim was to assess the risk of propofol infusions in the pediatric intensive care unit (PICU) at doses and durations greater than the described safety data and its associated covariables. Methods Retrospective cohort analysis of 173 patients receiving propofol in the PICU. Patients were categorized as receiving greater or less than 48 -hour infusions. Demographic data and daily clinical variables were recorded for up to seven days post -infusion initiation or until infusion was stopped. Results In this descriptive analysis, patients' demographics were similar, but admission diagnosis was not. Both groups received high mean doses of propofol (>67 mcg/kg/min), with no cases of PRIS observed. The illness severity scores and the need for vasoactive infusion support varied between the cohorts, with higher illness scores and a higher percentage of subjects requiring vasoactive agents in the >48 -hour cohort. Finally, there were no major differences in lactate levels or biochemical characteristics between the two groups. Conclusions This study provides pilot data in relation to the feasibility of propofol infusion in critically ill pediatric patients and underscores the need for a larger multicenter study to draw clinical recommendations.

To evaluate the use of inflammasome signaling proteins, specifically ASC, in serum as a prognostic tool in pediatric traumatic brain injury (pTBI).

Aim: Out-of-hospital cardiac arrest (OHCA) in pediatric patients is associated with high rates of mortality and neurologic injury, with no definitive evidence-based method to predict outcomes available. A prognostic scoring tool for adults, The Brain Death After Cardiac Arrest (BDCA) score, was recently developed and validated. We aimed to validate this score in pediatric patients.Methods: Retrospective cohort study of pediatric patients admitted to 5 PICUs after OHCA between 2011 and 2021. We extracted BDCA score elements for those who survived at least 24 hours but died as a result of their OHCA. We assessed score discrimination for the definitive outcome of brain death. Subgroup analysis was performed for infants < 12mo versus children >= 12mo, those who likely had brain death but had withdrawal of life sustaining therapy (WLST) prior to declaration, and by etiology and duration of arrest.Results: 389 subjects were identified across 5 institutions, with 282 meeting inclusion criteria. 169 (59.9%) were formally declared brain dead; 58 (20.6%) had findings consistent with brain death but had withdrawal of life sustaining therapies prior to completion of formal declaration. Area under the receiver operating characteristic curve for the age >= 12mo cohort was 0.82 [95% CI 0.75, 0.90], which mirrored the adult subject AUCs of 0.82 [0.77, 0.86] and 0.81 [0.76, 0.86] in the development and validation cohorts. Scores demonstrated worse discrimination in the infant cohort (AUC = 0.61).Conclusions: The BDCA score shows promise in children >= 12mo following OHCA and may be considered in conjunction with existing multimodal prognostication approaches.

Introduction: Fat emboli syndrome (FES) in the setting of sickle cell disease (SCD) occurs secondary to bone ischemia, releasing fatty acids into the blood, and leading to infarct and microhemorrhages to the brain through either pulmonary or cardiac shunt. The characteristic MRI findings of cerebral FES are a “starfield” appearance of scattered micro-infarcts. Cerebral FES is uncommon in pediatrics, in patients without evidence of a shunt and in patients without inciting bone injury. Description: 16 year old male with HbSS presented with low back pain concerning for acute vaso-occlusive pain crisis that progressed to acute chest syndrome, respiratory failure and ARDS requiring intubation. He had respiratory acidosis and prolonged hypoxia on arrival. His initial HgbS fraction was 76%, requiring multiple exchange transfusions. He developed multiorgan dysfunction including acute renal failure, bilateral cortical renal infarcts, and biventricular cardiac dysfunction with ejection fraction of 35-40% and no shunt. He received therapeutic plasma exchange (TPE) in the setting of thrombocytopenia with schistocytes. A week later, his respiratory failure had improved and sedation was lifted for extubation when he was found to have increased tone, myoclonic movements, clonus, extensor posturing, gaze deviation and bilateral Hoffman sign. EEG showed no evidence of seizures. MRI demonstrated diffuse microhemorrhages and diffusion restriction in the white matter of the brain, localized heavily in the corpus callosum, as well as extensive bone ischemia of cervical vertebrae consistent with a microvascular occlusive process. The bony changes and starfield pattern seen on MRI were suggestive of cerebral FES. He tested positive for parvovirus B19, commonly seen in FES. He was extubated 6 days after diagnosis of FES and transferred to rehab facility after a month. Discussion: Although well described in adults, we found only a single other case describing FES with SCD in a child. Also notable are his delayed development of FES after recovery from other organ injuries and in the absence of cardiac shunt, and unknown intrapulmonary shunt. Prognosis for this disease, particularly in pediatrics, is unclear and treatment is mostly supportive aside from exchange transfusions.

Introduction: The doctrine of double effect provides an ethical framework for providers to titrate medications to patient comfort at the end-of-life even if doing so hastens death, but moral distress may result from perceived under- or over- treatment. Objective of this study was to describe the doses of opioids and benzodiazepines (BZD) administered to children around the time of Terminal Extubation (TE) and to identify their association with the time to death (TTD). Methods: Secondary analysis of data collected for the Death One Hour After Terminal Extubation (DONATE) study, which included retrospective data from 9 U.S. hospitals. Medications included total doses of opioids and BZD 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression was performed to determine their association with TTD after adjusting for age, sex, last Saturation/FiO2 (SF) ratio, inotrope requirement in last 24 hours, and last recorded Glasgow Coma Scale (GCS) score. Results: Analysis cohort included 680 patients between 0-21 years who died within 1 hour in ICU after TE (2010-2021). Median age of the study population was 2.1 (IQR 0.4, 11) years. The median TTD was 15 (IQR 8, 23) minutes. 40% (278/680) of patients received either opioids or BZD within one hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent (eq) within 1 hour after TE was 0.75 (IQR 0 .3, 1.8) mg/kg/hr (n=263), and median lorazepam eq was 0.22 (IQR 0.11, 0.44) mg/kg/hr (n=118). The median morphine eq and lorazepam eq rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or BZD doses before or after TE and TTD. After adjusting for confounding variables regression analysis also failed to show any association between drug dose and TTD. Conclusions: Children after TE are often prescribed opioids and BZD. Time to death after TE is not associated with the dose of medication administered as part of comfort care. Providers should titrate analgesic and sedative/anxiolytic medications to patient comfort after terminal extubation.

Objectives:To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD). Design:Secondary analysis of data collected for the Death One Hour After Terminal Extubation study. Setting:Nine U.S. hospitals. Patients:Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010-2021). Measurements and Main Results:Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/Fio(2) ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) (n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/kg/hr) (n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD. Conclusions:Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care.

Key Clinical Message Cat‐scratch disease (CSD) is caused by Bartonella henselae and usually presents with regional lymphadenopathy. Skull base osteomyelitis and cerebral venous sinus thrombosis are rarely reported, particularly in immunocompetent children. CSD should be considered in the differential diagnosis of any patient with persistent headaches in the setting of cat exposure.

Introduction: In the PICU population, enteral nutrition (EN) as well as dexmedetomidine have been described as safe and effective with dexmedetomidine as the primary sedative of choice to improve tolerance of NIV. Methods to increase tolerance of NIV interfaces have been particularly important for patients < 24 months. We aimed to describe the potential association of EN with dexmedetomidine requirements for children on NIV. Here we describe a secondary aim to determine if there is a more pronounced association in the < 24 month population versus older children. Methods: A retrospective chart review was conducted of all children in our PICU acutely supported with NIV for at least 12 hours for a one-year period from April 1, 2019 - March 31, 2020. Data was collected until subjects were transferred out of the PICU, weaned off NIV, required intubation, or completed a max of 7 study days; whichever came first. Statistical comparisons were made using t-tests and chi-square tests for continuous and categorical variables, respectively. Results: 289 subjects were enrolled. 196 were < 24 months and 93 were older. On day 0, there were statistically significant differences (α = 0.05, p-value < 0.05) in the amount of children who received dexmedetomidine and were not fed and those who were fed in the < 24 month (50.7% versus 13.2%) and >25 month group (30.8% versus 11.1%). This continued for the younger group on day 1 with 69% not fed receiving dexmedetomidine versus 27.5% who were fed but lost its association for the older group past day 0. Conclusions: For critically ill children supported with NIV, there was a significant association with requirement of dexmedetomidine for patients who were not fed on day of initiation of NIV as previously presented. In this age-based subgroup analysis, this association was greater in the < 24 month age group than older children, supporting that feeding can potentially decrease sedation need even in this notoriously NIV intolerant group.