National and international hematopoietic stem cell transplantation (HSCT) societies recommend the use of early warning systems to detect clinical deterioration after pediatric HSCT. Commonly utilized tools, such as vital-sign-based early warning scores, do not incorporate pretransplantation risk factors, rely on categorization of vital sign ranges, and generate static scores applicable to single points in time. To predict the future need for (1) ICU transfer and (2) ICU transfer with critical intervention following pediatric allogeneic HSCT by integrating baseline demographic and transplant characteristics with dynamic changes in post-transplantation physiologic variables. Retrospective observational cohort study of patients admitted for first allogeneic HSCT at Children's National Hospital from January 1, 2012, through December 31, 2022. Patients were observed for ICU outcomes from transplantation to day 100 or hospital discharge. Statistical analyses included Kaplan-Meier survival analysis and time-dependent univariate and multivariate Cox proportional hazards regression. We also report 100-day and 1-year mortality. Among 307 pediatric HSCT recipients, 73 (24%) required ICU transfer and 37 (12%) received ≥1 critical intervention (invasive mechanical ventilation, vasoactive medication administration, and/or renal replacement therapy). The cumulative incidence of both outcomes plateaued by day 45 post-HSCT, with 65% of at-risk patients remaining free of ICU transfer and 81% free of ICU critical interventions. The final multivariate Cox proportional hazards models incorporated pretransplantation variables and dynamic post-transplantation physiologic changes, demonstrating excellent performance with daily C-statistics ranging from 0.83 to 0.86 for ICU transfer and 0.89 to 0.93 for ICU transfer with critical intervention. Overall mortality was 6% in 100 days and 15% in 1 year, but was higher among patients requiring ICU transfer (22% in 100 days, 37% in 1 year) and highest among those requiring critical interventions (38% in 100 days, 65% in 1 year). Dynamic modeling of pretransplantation factors and evolving post-transplantation physiologic trajectories can quantify the changing risk of clinical deterioration over time after pediatric HSCT. The performance of our models is appropriate for implementation, meeting the recommendations of national and international societies for the use of early warning systems. Implementation of dynamic early warning systems such as this may enable earlier recognition, enhanced surveillance, and potentially improved outcomes for high-risk patients.

OBJECTIVES:This study aimed to determine the decrease in opioid and benzodiazepine doses associated with the development of withdrawal in children.SETTING:Electronic health record data.INTERVENTION:None.PATIENTS:Four hundred and seven children who received invasive mechanical ventilation (IMV) between January 1, 2012 and January 1, 2022 with Withdrawal Assessment Tool-1 (WAT-1) scores during their IV opioid wean were included.MEASUREMENTS AND MAIN RESULTS:The primary outcome was development of withdrawal, defined as a WAT-1 score greater than or equal to 3, during the IV opioid weaning phase. Descriptive data included age, weight, insurance, race, ethnicity, language, comorbidities, length of stay, and IMV duration. WAT-1 scores were recorded, and the cumulative IV and enteral opioids, benzodiazepines, and A2As were calculated. Recent changes in IV opioid and benzodiazepine doses were assessed in the 16 hours before each WAT-1 score divided into 4-hour periods. Doses were compared across 4-hour periods, and a multivariable mixed-effects model was used to assess their association with withdrawal. The presence of greater than or equal to 2 pediatric complex chronic condition classification system version 2 (CCC-V2) diagnosis categories (odds ratio [OR] 3.35; 95% CI, 2.61-5.15) was associated with withdrawal. Heart disease, prematurity, and IV opioid class switching did not qualify for model inclusion. Cumulative IV opioid dose and a decrease in opioid exposure between 16-12 and 4-0 hours before the WAT-1 score were associated with withdrawal (OR 1.02; 95% CI, 1.01-1.03; OR 1.92; 95% CI, 1.38-3.16). Morphine was associated with increased odds of withdrawal compared with fentanyl and hydromorphone (OR 1.48; 95% CI, 1.37-1.81). The model did not establish an association between cumulative IV benzodiazepine exposure or IV benzodiazepine dose decrease and withdrawal.CONCLUSIONS:Patients with a higher cumulative IV opioid dose, an IV opioid wean in the preceding 8-12 hours, and greater than or equal to 2 CCC-V2 categories had the highest odds of withdrawal in this single-center study. Morphine was associated with increased odds of withdrawal as well.

IntroductionRenal dysfunction is common in critically ill children and increases morbidity and mortality risk. Diagnosis and management of renal dysfunction relies on creatinine, a delayed marker of renal injury. We aimed to develop and validate a machine learning model using routinely collected clinical data to predict 24-hour creatinine change in critically ill children before change is observed clinically.MethodsRetrospective cohort study of 39,932 pediatric intensive care unit encounters in a national multicenter database from 2007 to 2022. A neural network was trained to predict <50% or ≥50% creatinine change in the next 24 h. Admission demographics, routinely measured vital signs, laboratory tests, and medication use variables were used as predictors for the model. Data set was randomly split at the encounter level into model development (80%) and test (20%) sets. Performance and clinical relevance was assessed in the test set by accuracy of prediction classification and confusion matrix metrics.ResultsThe cohort had a male predominance (53.8%), median age of 8.0 years (IQR 1.9−14.6), 21.0% incidence of acute kidney injury, and 2.3% mortality. The overall accuracy of the model for predicting change of <50% or ≥50% was 68.1% (95% CI 67.6%−68.7%). The accuracy of classification improved substantially with higher creatinine values from 29.9% (CI 28.9%−31.0%) in pairs with an admission creatinine <0.3 mg/dl to 90.0–96.3% in pairs with an admission creatinine of ≥0.6 mg/dl. The model had a negative predictive value of 97.2% and a positive predictive value of 7.1%. The number needed to evaluate to detect one true change ≥50% was 14.Discussion24-hour creatinine change consistent with acute kidney injury can be predicted using routine clinical data in a machine learning model, indicating risk of significant renal dysfunction before it is measured clinically. Positive predictive performance is limited by clinical reliance on creatinine.

Rationale: Delayed (>5 minutes) epinephrine during pediatric in-hospital cardiac arrest (IHCA) is associated with worse outcomes. Epinephrine is nearly always given earlier, limiting 5 minutes as a quality target. Objectives: To assess early epinephrine administration (⩽2 minutes) on outcomes and hemodynamics during cardiopulmonary resuscitation (CPR) in pediatric IHCA from pulseless, nonshockable rhythms. Methods: This study leveraged the database of the ICU-RESUS (Intensive Care Unit Resuscitation) project (clinicaltrials.gov identifier NCT02837497). Primary exposure was the time to epinephrine bolus: early versus >2 minutes. Primary outcome was survival to discharge. Secondary outcomes included the return of spontaneous circulation (ROSC), survival with favorable neurologic outcome, change from baseline to discharge Functional Status Scale (FSS) score, total FSS score at discharge, new morbidity among survivors, and invasively measured blood pressure during the first 10 minutes of CPR. Results: Among 352 CPR events, median age was 1.0 (interquartile range [IQR], 0.3-8.0) year, 186 (53%) were male, and 185 (52.6%) had cardiac disease. Early epinephrine was administered in 273 (78%), and median time to administration was 1.0 (0.0-2.0) minute. Survival to discharge was similar between patients who received early epinephrine and those who did not. Early epinephrine administration was associated with higher ROSC, a change from baseline to discharge in FSS, lower total FSS scores at discharge, and lower rates of new morbidity compared with epinephrine administration at >2 minutes. The probability of ROSC and survival to discharge with favorable neurologic outcome decreased for each minute of delay in epinephrine administration. There was no difference in the invasive blood pressure targets during the first 10 minutes of CPR. Conclusions: Early epinephrine administration was common and was associated with higher ROSC and improved functional outcomes compared with epinephrine administration at >2 minutes in pediatric IHCA.

Introduction In 2024, a Society of Critical Care Medicine task force updated the pediatric sepsis definition from the presence of suspected or confirmed infection, and a systemic inflammatory response (SIRS) with organ dysfunction, to a novel definition. Our objective is to identify how many patients previously identified as having severe sepsis would continue to meet the new definition. Materials and methods We performed a secondary analysis of the Phenotyping Sepsis-Induced Multiple Organ Failure cohort of 401 children with suspected or confirmed infection, two of four SIRS criteria and organ dysfunction enrolled between 2015-2017. We calculated a modified Phoenix Sepsis Criteria Score (mPSC) for participants and compared those with mPSC of greater than or equal to 2 or less than 2 according to the 2024 definition. Results Of 401 children, 132 (33%) did not meet mPSC definitions. While children meeting mPSC had more organ dysfunction, the total mortality did not differ. One in 4 children requiring extracorporeal membrane oxygenation and 1 in 4 mortalities did not meet the mPSC definition. In logistic regression models, in the complete cohort, hematologic (OR 4.4, 95% CI: 1.8-10.2, P -value = .001), central nervous system (OR 2.3, 95% CI: 1.0-5.1, P -value = .046) and renal failure (OR: 3.2, 95% CI:1.2-7.9, P -value = .017) predicted mortality; in the mPSC subgroup pulmonary (OR: 3.6, 95% CI:1.3-13.3, P -value = .030) and hematologic failure (OR 5.6, 95% CI: 2.2-14.5, P -value = .0003) were significant predictors. In the mPSC excluded subgroup, only renal failure predicted mortality (OR 9.6, 95% CI 1.1-73.0, P -value = .028). Conclusions Further study of the impact of the 2024 data-driven organ dysfunction definition on pediatric sepsis research, patient safety, and clinical benchmarking efforts is warranted.

OBJECTIVES:Prearrest sepsis has been associated with particularly poor outcomes among children who suffer in-hospital cardiac arrest (IHCA), but there is a paucity of dedicated studies on the topic. In this study of children receiving cardiopulmonary resuscitation (CPR) in the ICU, our objective was to determine the associations of sepsis with IHCA outcomes and intraarrest physiology. DESIGN:Prospectively designed secondary analysis of the ICU Resuscitation Project clinical trial (NCT02837497). SETTING:The 18 pediatric and pediatric cardiac ICUs at ten children's hospitals in the United States. PATIENTS:Children (≤ 18 yr) with an index IHCA event. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The primary exposure was a prearrest diagnosis of sepsis. The primary survival outcome was survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline). The primary physiologic outcome was average diastolic blood pressure (DBP) during CPR. Multivariable regression models controlling for a priori covariates assessed the relationship between sepsis and outcomes. Of 1129 children with index IHCAs, 184 (16.3%) had prearrest sepsis. Patients with sepsis had greater prearrest comorbidities, higher prearrest severity of illness, and higher Vasoactive-Inotropic Scores than patients without sepsis. They more frequently had hypotension as the cause of IHCA, had longer durations of CPR, and more frequently received epinephrine and sodium bicarbonate during CPR. They less frequently achieved survival with favorable neurologic outcome (52/184 [28.3%] vs. 552/945 [58.4%]; p < 0.001; adjusted relative risk, 0.54; 95% CI, 0.43-0.68; p < 0.001). Intraarrest DBPs did not differ between patients with vs. without sepsis. Following IHCA, event survivors with sepsis had higher vasoactive requirements, more frequently experienced hypotension, and continued to have greater mortality rates through 48 hours postarrest. CONCLUSIONS:Children with prearrest sepsis had worse survival outcomes, similar intraarrest DBPs, and greater pre and postarrest severity of illness than children without sepsis.

Iatrogenic withdrawal syndrome (IWS) is a significant yet underrecognized public health concern for pediatric patients in critical care units, most frequently the result of abrupt cessation or rapid tapering of sedative or opioid medications. Early prediction of IWS is important for timely intervention and improved patient outcomes. In this study, we developed an explainable deep learning model utilizing a unidirectional multilayer long short-term memory (LSTM) network to predict the risk of IWS in pediatric ICU patients. Through longitudinal electronic health records (EHRs), our model analyzes the preceding 24 hours of patient data to predict the likelihood of IWS occurring in the next four hours, providing a real-time risk score. To enhance interpretability and identify key risk factors, we applied layer-wise relevance propagation (LRP) to the LSTM model. The feature importance rankings derived from LRP were validated through multiple experiments. Experimental results show that the model was perfectly calibrated and achieved robust predictive performance, suggesting that the LRP enhanced LSTM model holds significant potential for improving pediatric patient care by facilitating early detection and proactive management of IWS in critical care settings. Implementing this model into a system of alerts for clinicians could lead to significant advances in safer sedative and analgesic use, addressing an under addressed public health issue that impacts not only the United States but also the global community.

OBJECTIVE:To assess patient characteristics and care factors that are associated with correct and incorrect predictions of future care locations (ICU vs. non-ICU) by the Criticality Index-Dynamic (CI-D), with the goal of enhancing the CI-D. DESIGN:Retrospective structured chart review. PARTICIPANTS:All pediatric inpatients admitted from January` 1st 2018 - February 29th 2020 through the emergency department. MAIN OUTCOME(S) AND MEASURE(S):Patient characteristics and care factors associated with correct (true positives, true negatives) and incorrect predictions (false positives, false negatives) of future care locations (ICU vs. non-ICU) by the CI-D were assessed. RESULTS:Of the 3,018, patients, 139 transitioned from non-ICU locations to ICU care; 482 were transferred from the ICU to non-ICU care locations, and 2,400 remained in non-ICU care locations. For the ICU Prediction group, the false negative patients were older, more frequently male, and had longer hospital and ICU lengths of stay compared to the true positive patients. The significant differences in the ICU Prediction group for false negative compared to the true positive patients included a less frequent: primary diagnosis of respiratory failure, use of high flow nasal canula, hourly cardio-respiratory vital signs prior to transfer to the ICU, and neurologic vital signs after transfer from the ICU. For the ICU Discharge prediction group, false positive patients were more frequently: younger, had a primary diagnosis of respiratory failure, more frequently received respiratory support after discharge from the ICU, and received less frequent neurological vital signs prior to transfer from the ICU. For the Non-transfer prediction category, demographics and clinical variables did not differ between the true negative and false positive prediction groups. CONCLUSION AND RELEVANCE:We conducted the first comprehensive analysis via structured chart reviews of patient characteristics and care factors that are associated with correct and incorrect predictions of future care locations by the machine learning algorithm, the CI-D, gaining insights into potential new predictor variables for inclusion in the model to improve future model iterations.

Sepsis is a leading global health burden in children, and its unavoidable heterogeneity has hindered providing therapies beyond antibiotics and supportive care. Recently, we identified four computable phenotypes showing distinct cytokine profiles, clinical outcomes, and therapeutic response characteristics (PedSep-A, B, C, and D) in a multicenter pediatric sepsis cohort. In the cohort data, we collected whole-exome sequencing data and identified rare variants associated with PedSep-D phenotype by conducting a gene-based analysis in an aggregated fashion. As a result, one whole-exome significant gene (LTBP4) and two suggestive significant genes (PLA2G4E, CCDC157) showed association with PedSep-D, the phenotype characterized by the most severe outcomes and highest inflammation. The associated variants in LTBP4 were enriched for predicted deleterious effects based on established functional prediction metrics. All three associated genes are implicated in inflammation and immune cell activation based on existing gene function and expression data. Although the circulating cytokine profiles were overlapping between the rare variant carriers, we also identified gene-specific cytokine changes. Altogether, our study provides valuable insights into the genetic architecture of a pediatric sepsis phenotype with the highest inflammation level and the most severe outcomes, highlighting potential candidate genes and pathways for further biomarker and therapeutic studies.

ImportanceSepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis.ObjectiveTo assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study.Design, Setting, and ParticipantsThis cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG antibodies to CMV, EBV, HSV-1, or HHV-6. A total of 401 patients younger than 18 years with severe sepsis were enrolled from 9 pediatric intensive care units (PICUs) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Data were collected from 2015 to 2018. Samples were assayed from 2019 to 2022. Data were analyzed from 2022 to 2023.Main Outcomes and MeasuresDeath while in the PICU.ResultsAmong the 401 patients included in the analysis, the median age was 6 (IQR, 1-12) years, and 222 (55.4%) were male. One hundred fifty-four patients (38.4%) were previously healthy, 108 (26.9%) were immunocompromised, and 225 (56.1%) had documented infection(s) at enrollment. Forty-four patients (11.0%) died in the PICU. Viral DNAemia with at least 1 virus (excluding TTV) was detected in 191 patients (47.6%) overall, 63 of 108 patients (58.3%) who were immunocompromised, and 128 of 293 (43.7%) who were not immunocompromised at sepsis onset. After adjustment for age, Pediatric Risk of Mortality score, previously healthy status, and immunocompromised status at sepsis onset, CMV (adjusted odds ratio [AOR], 3.01 [95% CI, 1.36-6.45]; P = .007), HAdV (AOR, 3.50 [95% CI, 1.46-8.09]; P = .006), BKPyV (AOR. 3.02 [95% CI, 1.17-7.34]; P = .02), and HHV-6 (AOR, 2.62 [95% CI, 1.31-5.20]; P = .007) DNAemia were each associated with increased mortality. Two or more viruses were detected in 78 patients (19.5%), with mortality among 12 of 32 (37.5%) who were immunocompromised and 9 of 46 (19.6%) who were not immunocompromised at sepsis onset. Herpesvirus seropositivity was common (HSV-1, 82 of 246 [33.3%]; CMV, 107 of 254 [42.1%]; EBV, 152 of 251 [60.6%]; HHV-6, 253 if 257 [98.4%]). After additional adjustment for receipt of blood products in the PICU, EBV seropositivity was associated with increased mortality (AOR, 6.10 [95% CI, 1.00-118.61]; P = .049).Conclusions and RelevanceThe findings of this cohort study suggest that DNAemia for CMV, HAdV, BKPyV, and HHV-6 and EBV seropositivity were independently associated with increased sepsis mortality. Further investigation of the underlying biology of these viral DNA infections in children with sepsis is warranted to determine whether they only reflect mortality risk or contribute to mortality.

Objective: Develop an inpatient predictive model of parental post-traumatic stress (PTS) following their child's care in the Pediatric Intensive Care Unit (PICU). Design: Prospective observational cohort. Setting: Two tertiary care children's hospitals with mixed medical/surgical/cardiac PICUs. Subjects: Parents of patients admitted to the PICU. Interventions: None. Measurements and Main Results: Preadmission and admission data from 169 parents of 129 children who completed follow up screening for parental post-traumatic stress symptoms at 3-9 months post PICU discharge were utilized to develop a predictive model estimating the risk of parental PTS 3-9 months after hospital discharge. The parent cohort was predominantly female (63%), partnered (75%), and working (70%). Child median age was 3 years (IQR 0.36-9.04), and more than half had chronic illnesses (56%) or previous ICU admissions (64%). Thirty-five percent (60/169) of parents met criteria for PTS (>9 on the Post-traumatic Stress Disorder Symptom Scale-Interview). The machine learning model (XGBoost) predicted subjects with parental PTS with 76.7% accuracy, had a sensitivity of 0.83 (95% CI 0.586, 0.964), a specificity of 0.72 (95% CI 0.506, 0.879), a precision of 0.682 (95% CI 0.451, 0.861) and number needed to evaluate of 1.47 (95% CI 1.16, 1.98). The area under the receiver operating curve was 0.78 (95% CI 0.64, 0.92). The most important predictive pre-admission and admission variables were determined using the Local Interpretable Model-Agnostic Explanation, which identified seven variables used 100% of the time. Composite variables of parental history of mental illness and traumatic experiences were most important. Conclusion: A machine learning model using parent risk factors predicted subsequent PTS at 3-9 months following their child's PICU discharge with an accuracy of 76.7% and number needed to evaluate of 1.47. This performance is sufficient to identify parents who are at risk during hospitalization, making inpatient and acute post admission mitigation initiatives possible.

OBJECTIVES:To examine career trajectory and academic profile of Pediatric Critical Care Medicine (PCCM) physicians, with special focus on gender differences. DESIGN:Observational cross-sectional study of PCCM fellowship graduates using publicly available data. SETTING:Publicly available databases including National Provider Identifier registry, American Board of Pediatrics, Doximity, official hospital websites, and Scopus. SUBJECTS:Two thousand one hundred twenty-nine PCCM fellowship graduates employed in clinical positions in U.S. practice locations. INTERVENTION:None. MEASUREMENTS AND MAIN RESULTS:Physician demographic characteristics included gender and time since fellowship completion. Current career and academic characteristics included employment data, publication productivity (h-index), and academic rank. Data from 2129 career PCCM physicians was included, with recent graduates showing a notable increase in female representation. Workplace characteristics revealed that most PCCM physicians worked in university-affiliated hospitals, with higher percentages of female physicians working in university-affiliated hospitals compared with male physicians. The study also highlighted significant gender disparities in academic metrics, with male physicians having higher h-indices (3 vs. 2; p < 0.001) and more publications (6 vs. 4; p < 0.001) than their female counterparts across various career phases. Additionally, the analysis showed gender differences in academic rank, with a higher proportion of female faculty holding assistant and associate professor ranks (58.2% vs. 47.5%; p < 0.001), while a greater percentage of male faculty held the rank of professor (20.2% vs. 11.1%; p < 0.001). Multiple variable regression analysis identified both male gender and time since fellowship graduation as independently associated with a physician's h-index, while only time since fellowship graduation was linked to current academic rank. CONCLUSIONS:This is the first analysis of career and academic characteristics of practicing PCCM physicians, additionally studying the association of gender and career trajectory. Gender discrepancy was seen in employment hospital characteristics, h-indices, and academic rank. Additional studies are required to further explore the impact of gender on career trajectory.

Shanklin, Alice; Trujillo Rivera, Eduardo; Pollack, Murray; Patel, Anita Author Information

OBJECTIVES:Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes. DESIGN:This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing. SETTING:Eighteen PICUs and pediatric cardiac ICUs in the United States. PATIENTS:Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded. INTERVENTIONS:The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. MEASUREMENTS AND MAIN RESULTS:The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01). CONCLUSIONS:In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

Rationale: Adult and pediatric studies provide conflicting data regarding whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia, and/or hypocapnia are associated with worse outcomes. Objectives: We sought to determine whether postarrest hypoxemia or postarrest hyperoxemia is associated with lower rates of survival to hospital discharge, compared with postarrest normoxemia, and whether postarrest hypocapnia or hypercapnia is associated with lower rates of survival, compared with postarrest normocapnia. Methods: An embedded prospective observational study during a multicenter interventional cardiopulmonary resuscitation trial was conducted from 2016 to 2021. Patients ⩽18 years old and with a corrected gestational age of ≥37 weeks who received chest compressions for cardiac arrest in one of the 18 intensive care units were included. Exposures during the first 24 hours postarrest were hypoxemia, hyperoxemia, or normoxemia-defined as lowest arterial oxygen tension/pressure (PaO2) <60 mm Hg, highest PaO2 ⩾200 mm Hg, or every PaO2 60-199 mm Hg, respectively-and hypocapnia, hypercapnia, or normocapnia, defined as lowest arterial carbon dioxide tension/pressure (PaCO2) <30 mm Hg, highest PaCO2 ⩾50 mm Hg, or every PaCO2 30-49 mm Hg, respectively. Associations of oxygenation and carbon dioxide group with survival to hospital discharge were assessed using Poisson regression with robust error estimates. Results: The hypoxemia group was less likely to survive to hospital discharge, compared with the normoxemia group (adjusted relative risk [aRR] = 0.71; 95% confidence interval [CI] =  0.58-0.87), whereas survival in the hyperoxemia group did not differ from that in the normoxemia group (aRR = 1.0; 95% CI = 0.87-1.15). The hypercapnia group was less likely to survive to hospital discharge, compared with the normocapnia group (aRR = 0.74; 95% CI = 0.64-0.84), whereas survival in the hypocapnia group did not differ from that in the normocapnia group (aRR = 0.91; 95% CI = 0.74-1.12). Conclusions: Postarrest hypoxemia and hypercapnia were each associated with lower rates of survival to hospital discharge.

OBJECTIVES:To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months.DESIGN:Secondary analysis of a prospective multisite cohort study.SETTING:Eight academic PICUs in the United States (2019-2020).PATIENTS:Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event.INTERVENTIONS:None.METHODS AND MEASUREMENT:We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months.MAIN RESULTS:Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not.CONCLUSIONS:Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.

OBJECTIVES:Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs). DESIGN:This is an analysis of of a seven-center prospective cohort study. SETTING:Seven PICUs within academic children's hospitals in the United States. PATIENTS:Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours. INTERVENTIONS:We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement. MEASUREMENTS AND MAIN RESULTS:Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001). CONCLUSIONS:Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.

Background: Resuscitation with chest compressions and positive pressure ventilation in Bidirectional Glenn (BDG) or Fontan physiology may compromise passive venous return and accentuate neurologic injury. We hypothesized that arterial pressure and survival would be better in BDG than Fontan patients. Methods: Secondary analyses of the Pediatric Intensive Care Quality of CPR and Improving Outcomes from Pediatric Cardiac Arrest databases. P-values were considered significant if < 0.05. Results: In total, 64 patients had either BDG (42/64, 66%) or Fontan (22/64, 34%) anatomy. Return of spontaneous circulation was achieved in 76% of BDG patients versus 59% of Fontan patients and survival with favorable neurologic outcome in 22/42 (52%) BDG versus 6/22 (27%) Fontan patients, p = 0.067. Twelve of 24 (50%) BDG and 2/7 (29%) Fontan patients who survived to discharge suffered new morbidity as defined by worsening Functional Status Score. More BDG patients achieved adequate DBP (>= 25 mmHg for neonates and infants; >= 30 mmHg for children) than Fontan patients (21/23 (91%) vs. 5/11 (46%), p = 0.007). Conclusions: Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after CPR, likely driven by inadequate diastolic blood pressure during resuscitation. One half of the BDG patients who survived to hospital discharge had new neurologic morbidity. BackgroundCardiac arrest in patients with congenital heart disease (CHD) may present challenges to resuscitation based on the unique cardiovascular physiology resulting from surgical palliation. Recent resuscitation guidelines for CHD patients highlight the lack of data surrounding these special patient populations.1 Univentricular heart disease is palliated by a series of cardiac surgeries that stepwise result in passive pulmonary perfusion from the systemic venous system directly to the pulmonary vascular bed. The bidirectional Glenn (BDG) palliation directly anastomoses the superior vena cava (SVC) to the pulmonary arterial system and leaves normal inferior vena cava (IVC) venous return to the heart.2 The Fontan palliation baffles IVC flow directly to the pulmonary vascular bed which relieves cyanosis due to right to left shunting, but requires systemic ventricular preload to be directly dependent upon pulmonary vascular resistance and intrathoracic pressures.3 Impact statementHemodynamic waveforms from 2 large prospective observational studies now allow for exploration of physiology during cardiopulmonary resuscitation for unique anatomy associated with single ventricle congenital heart disease.Fewer patients with Fontan physiology (46%) achieved an adequate diastolic blood pressure (defined as >= 25 mmHg for neonates and infants and >= 30 mmHg for children) than bidirectional Glenn patients during cardiopulmonary resuscitation (91%, = 0.007).Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after cardiopulmonary resuscitation.Of the bidirectional Glenn patients who survived, 50% developed a new morbidity as quantified by the Functional Status Score.

ImportanceBronchiolitis is the most common diagnosis necessitating respiratory support and pediatric intensive care, and respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. In 2023, the monoclonal antibody nirsevimab and the maternal RSVpreF vaccine were implemented to prevent RSV in infants.ObjectiveTo determine the potential association of novel RSV prevention strategies with pediatric intensive care unit (ICU) utilization.Design, Setting, and ParticipantsThis retrospective cross-sectional study examined US pediatric ICU encounters with and without RSV from January 1, 2017, to June 1, 2023. Data were from Oracle Cerner RealWorld Data, a national electronic health record database. All children (aged >1 day and <18 years) admitted to an ICU during the study period were included in the analysis. Statistical analysis was performed from February to May 2024.Main Outcomes and MeasuresThe primary outcomes were ICU encounters with RSV and ICU encounters with RSV eligible for RSV prevention.ResultsThere were 119 782 ICU encounters from 53 hospitals; 65 757 encounters (54.9%) were male; median (IQR) age was 4.5 (1.1-12.5) years, median (IQR) ICU length of stay was 1.8 (1.0-3.9) days; 13 702 ICU encounters (11.4%) had RSV, of which 38.6% (5217) were eligible for prevention (4.4% of total ICU encounters). Encounters with RSV accounted for 21.1% (109 334) of ICU days, of which 43.8% (47 888) were eligible for prevention (9.2% of total ICU days). Encounters with RSV were associated with a greater use of positive pressure ventilation (4074 [29.7%] vs 18 821 [17.7%]; P < .001) and vasoactive medications (3057 [22.3%] vs 18 570 [17.5%]; P < .001) compared with those without RSV.Conclusions and RelevanceThe findings of this retrospective cross-sectional study of RSV and US pediatric intensive care utilization suggest that if 65% to 85% of eligible children received RSV prevention, an estimated 2.1% to 2.8% reduction in pediatric ICU encounters and an estimated 4.5% to 5.9% reduction in pediatric ICU days could be achieved.