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Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks.A prospective, observational cohort study.Children with sepsis and organ failure in nine pediatric intensive care units in the United States.Two hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin.Group 1 had normal CRP and ferritin levels ( n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout ( n = 80; 5% mortality); Group 3 had high ferritin levels alone ( n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels ( n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels ( n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines.Bedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies.

To evaluate associations between sodium bicarbonate use and outcomes during pediatric in-hospital cardiac arrest (p-IHCA).Prespecified secondary analysis of a prospective, multicenter cluster randomized interventional trial.Eighteen participating ICUs of the ICU-RESUScitation Project (NCT02837497).Children less than or equal to 18 years old and greater than or equal to 37 weeks post conceptual age who received chest compressions of any duration from October 2016 to March 2021.None.Child and event characteristics, prearrest laboratory values (2-6 hr prior to p-IHCA), pre- and intraarrest hemodynamics, and outcomes were collected. In a propensity score weighted cohort, the relationships between sodium bicarbonate use and outcomes were assessed. The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Of 1,100 index cardiopulmonary resuscitation events, median age was 0.63 years (interquartile range, 0.19-3.81 yr); 528 (48.0%) received sodium bicarbonate; 773 (70.3%) achieved ROSC; 642 (58.4%) survived to hospital discharge; and 596 (54.2%) survived to hospital discharge with favorable neurologic outcome. Among the weighted cohort, sodium bicarbonate use was associated with lower survival to hospital discharge rate (adjusted odds ratio [aOR], 0.7; 95% CI, 0.54-0.92; p = 0.01) and lower survival to hospital discharge with favorable neurologic outcome rate (aOR, 0.69; 95% CI, 0.53-0.91; p = 0.007). Sodium bicarbonate use was not associated with ROSC (aOR, 0.91; 95% CI, 0.62-1.34; p = 0.621).In this propensity weighted multicenter cohort study of p-IHCA, sodium bicarbonate use was common and associated with lower rates of survival to hospital discharge.

Children with obesity frequently have functional impairment after critical illness. Although obesity increases morbidity risk after trauma, the association with functional outcomes in children is unknown.To evaluate the association of weight with functional impairment at hospital discharge in children with serious injuries.This secondary analysis of a multicenter prospective study included children15 years old with a serious injury. Four weight groups, underweight, healthy weight, overweight, and obesity/severe obesity were defined by body mass index z-scores. The functional status scale (FSS) measured impairment across six functional domains before injury and at hospital discharge. New domain morbidity was defined as a change ≥2 points. The association between weight and functional impairment was determined using logistic regression adjusting for demographics, physiological measures, injury details, presence of a severe head injury, and physical abuse.Although most patients discharged with good/unchanged functional status, new domain morbidity occurred in 74 patients (17%). New FSS domain morbidity occurred in 13% of underweight, 14% of healthy weight, 15% of overweight, and 26% of obese/severe obese patients. Compared to healthy weight patients, those with obesity had more frequent new domain morbidity (p = 0.01), while the other weight groups had similar morbidity. However, after adjustment for confounders, weight was not associated with new functional morbidity at discharge.Patients with obesity have greater frequency of new domain morbidity after a serious injury; however, after accounting for injury characteristics, weight group is not independently associated with new functional morbidity at hospital discharge after injury in children.III.

Corticosteroids are commonly used in the treatment of pediatric septic shock without clear evidence of the potential benefits or risks. This study examined the association of early corticosteroid therapy with patient-centered clinically meaningful outcomes.Subsequent cohort analysis of data derived from the prospective Life After Pediatric Sepsis Evaluation (LAPSE) investigation. Outcomes among patients receiving hydrocortisone or methylprednisolone on study day 0 or 1 were compared with those who did not use a propensity score-weighted analysis that controlled for age, sex, study site, and measures of first-day illness severity.Twelve academic PICUs in the United States.Children with community-acquired septic shock 1 month to 18 years old enrolled in LAPSE, 2013-2017. Exclusion criteria included a history of chronic corticosteroid administration.None.Among children enrolled in LAPSE, 352 of 392 met analysis inclusion criteria, and 155 of 352 (44%) received early corticosteroid therapy. After weighting corticosteroid therapy administration propensity across potentially confounding baseline characteristics, differences in outcomes associated with treatment were not statistically significant (adjusted effect or odds ratio [95% CI]): vasoactive-inotropic support duration (-0.37 d [-1.47 to 0.72]; p = 0.503), short-term survival without new morbidity (1.37 [0.83-2.28]; p = 0.218), new morbidity among month-1 survivors (0.70 [0.39-1.23]; p = 0.218), and persistent severe deterioration of health-related quality of life or mortality at month 1 (0.70 [0.40-1.23]; p = 0.212).This study examined the association of early corticosteroid therapy with mortality and morbidity among children encountering septic shock. After adjusting for variables with the potential to confound the relationship between early corticosteroid administration and clinically meaningful end points, there was no improvement in outcomes associated with this therapy. Results from this propensity analysis provide additional justification for equipoise regarding corticosteroid therapy for pediatric septic shock and ascertain the need for a well-designed clinical trial to examine benefit/risk for this intervention.

OBJECTIVE To 1) determine current intravenous (IV) acetaminophen use in pediatric inpatients; and 2) determine the association between opioid medication duration when used with or without IV acetaminophen. METHODS A retrospective analysis of pediatric inpatients exposed to IV acetaminophen from January 2011 to June 2016, using the national database Health Facts. RESULTS Eighteen thousand one hundred ninety-seven (2.0%) of 893,293 pediatric inpatients received IV acetaminophen for a median of 14 doses per patient (IQR, 8–56). A greater proportion of IV acetaminophen patients were admitted to the intensive care unit (ICU) (14.8% vs 5.1%, p < 0.0001), received positive pressure ventilation (2.0% vs 1.5%, p < 0.0001), had a higher hospital mortality rate (0.9% vs 0.3%, p < 0.0001), and were operative (35.5% vs 12.8%, p < 0.001) than those not receiving IV acetaminophen. The most common operations associated with IV acetaminophen use were musculoskeletal and digestive system operations. Prescription of IV acetaminophen increased over time, both in prescription rates and number of per patient doses. Of the 18,197 patients prescribed IV acetaminophen, 16,241 (89.2%) also were prescribed opioids during their hospitalization. A multivariate analysis revealed patients prescribed both IV acetaminophen and opioids had a 54.8% increase in opioid duration as compared with patients who received opioids alone. CONCLUSIONS This is the first study to assess IV acetaminophen prescription practices for pediatric inpatients. Intravenous acetaminophen prescription was greater in the non-operative pediatric inpatient population than operative patients. Intravenous acetaminophen prescription was associated with an increase in opioid duration as compared with patients who received opioids alone, suggesting that it is commonly used to supplement opioids for pain relief.

Characterize the use of inhaled nitric oxide (iNO) for pediatric cardiac patients and assess the relationship between patient characteristics before iNO initiation and outcomes following cardiac surgery.Observational cohort study.PICU and cardiac ICUs in seven Collaborative Pediatric Critical Care Research Network hospitals.Consecutive patients, less than 18 years old, mechanically ventilated before or within 24 hours of iNO initiation. iNO was started for a cardiac indication and excluded newborns with congenital diaphragmatic hernia, meconium aspiration syndrome, and persistent pulmonary hypertension, or when iNO started at an outside institution.None.Four-hundred seven patients with iNO initiation based on cardiac dysfunction. Cardiac dysfunction patients were administered iNO for a median of 4 days (2-7 d). There was significant morbidity with 51 of 407 (13%) requiring extracorporeal membrane oxygenation and 27 of 407 (7%) requiring renal replacement therapy after iNO initiation, and a 28-day mortality of 46 of 407 (11%). Of the 366 (90%) survivors, 64 of 366 patients (17%) had new morbidity as assessed by Functional Status Scale. Among the postoperative cardiac surgical group (n = 301), 37 of 301 (12%) had a superior cavopulmonary connection and nine of 301 (3%) had a Fontan procedure. Based on echocardiographic variables prior to iNO (n = 160) in the postoperative surgical group, right ventricle dysfunction was associated with 28-day and hospital mortalities (both, p0.001) and ventilator-free days (p = 0.003); tricuspid valve regurgitation was only associated with ventilator-free days (p0.001), whereas pulmonary hypertension was not associated with mortality or ventilator-free days.Pediatric patients in whom iNO was initiated for a cardiac indication had a high mortality rate and significant morbidity. Right ventricular dysfunction, but not the presence of pulmonary hypertension on echocardiogram, was associated with ventilator-free days and mortality.

Purpose Our understanding of inborn errors of immunity is increasing; however, their contribution to pediatric sepsis is unknown. Methods We used whole-exome sequencing (WES) to characterize variants in genes related to monogenic immunologic disorders in 330 children admitted to intensive care for severe sepsis. We defined candidate variants as rare variants classified as pathogenic or potentially pathogenic in QIAGEN’s Human Gene Mutation Database or novel null variants in a disease-consistent inheritance pattern. We investigated variant correlation with infection and inflammatory phenotype. Results More than one in two children overall and three of four African American children had immunodeficiency-associated variants. Children with variants had increased odds of isolating a blood or urinary pathogen (blood: OR 2.82, 95% CI: 1.12–7.10, p = 0.023, urine: OR: 8.23, 95% CI: 1.06–64.11, p = 0.016) and demonstrating increased inflammation with hyperferritinemia (ferritin $$\ge 500$$ ≥ 500 ng/mL, OR: 2.16, 95% CI: 1.28–3.66, p = 0.004), lymphopenia (lymphocyte count p = 0.027), thrombocytopenia (platelet count p = 0.013), and CRP greater than 10 mg/dl (OR: 1.71, 95% CI: 1.10–2.68, p = 0.017). They also had increased odds of requiring extracorporeal membrane oxygenation (ECMO, OR: 4.19, 95% CI: 1.21–14.5, p = 0.019). Conclusion Herein, we describe the genetic findings in this severe pediatric sepsis cohort and their microbiologic and immunologic significance, providing evidence for the phenotypic effect of these variants and rationale for screening children with life-threatening infections for potential inborn errors of immunity.

Background Retaining participants over time is a frequent challenge in research studies evaluating long-term health outcomes. This study’s objective was to compare the impact of prepaid and postpaid incentives on response to a six-month follow-up survey. Methods We conducted an experiment to compare response between participants randomized to receive either prepaid or postpaid cash card incentives within a multisite study of children under 15 years in age who were hospitalized for a serious, severe, or critical injury. Participants were parents or guardians of enrolled children. The primary outcome was survey response. We also examined whether demographic characteristics were associated with response and if incentive timing influenced the relationship between demographic characteristics and response. We evaluated whether incentive timing was associated with the number of calls needed for contact. Results The study enrolled 427 children, and parents of 420 children were included in this analysis. Follow-up survey response did not differ according to the assigned treatment arm, with the percentage of parents responding to the survey being 68.1% for the prepaid incentive and 66.7% with the postpaid incentive. Likelihood of response varied by demographics. Spanish-speaking parents and parents with lower income and lower educational attainment were less likely to respond. Parents of Hispanic/Latino children and children with Medicaid insurance were also less likely to respond. We found no relationship between the assigned incentive treatment and the demographics of respondents compared to non-respondents. Conclusions Prepaid and postpaid incentives can obtain similar participation in longitudinal pediatric critical care outcomes research. Incentives alone do not ensure retention of all demographic subgroups. Strategies for improving representation of hard-to-reach populations are needed to address health disparities and ensure the generalizability of studies using these results.

Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort.Prospective observational study.Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020.Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR.None.Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051).These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR.

ObjectivesThe COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes.DesignMulticenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021).SettingData source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial.PatientsChildren (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS.InterventionsNone.Measurements and main resultsAmong 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46]; p = 0.04).ConclusionsUsing the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

To evaluate associations between calcium administration and outcomes among children with in-hospital cardiac arrest and among specific subgroups in which calcium use is hypothesized to provide clinical benefit.This is a secondary analysis of observational data collected prospectively as part of the ICU-RESUScitation project. Children 37 weeks post-conceptual age to 18 years who received chest compressions in one of 18 intensive care units from October 2016-March 2021 were eligible. Data included child and event characteristics, pre-arrest laboratory values, pre- and intra-arrest haemodynamics, and outcomes. Outcomes included sustained return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with favourable neurologic outcome. A propensity score weighted cohort was used to evaluate associations between calcium use and outcomes. Subgroups included neonates, and children with hyperkalaemia, sepsis, renal insufficiency, cardiac surgery with cardiopulmonary bypass, and calcium-avid cardiac diagnoses.Of 1,100 in-hospital cardiac arrests, median age was 0.63 years (IQR 0.19, 3.81); 450 (41%) received calcium. Among the weighted cohort, calcium use was not associated with sustained ROSC (aOR, 0.87; CI95 0.61-1.24; p=0.445), but was associated with lower rates of both survival to hospital discharge (aOR, 0.68; CI95 0.52-0.89; p=0.005) and survival with favourable neurologic outcome at hospital discharge (aOR, 0.75; CI95 0.57-0.98; p=0.038). Among subgroups, calcium use was associated with lower rates of survival to hospital discharge in children with sepsis and renal insufficiency.Calcium use was common during paediatric in-hospital cardiac arrest and associated with worse outcomes at hospital discharge.

Background: Parents often suffer reduced mental health after their child’s death; however, the trajectory and risk factors are not well described. Objective: Describe the change in complicated grief, depression, and post-traumatic stress symptoms among parents between 6 and 13 months after their child’s death in a pediatric intensive care unit (PICU), and factors associated with 13-month symptoms. Methods: Parents whose children died in 1 of 8 PICUs affiliated with the Collaborative Pediatric Critical Care Research Network completed surveys 6 and 13 months after their child’s death. Surveys included the Inventory of Complicated Grief (ICG), the Patient Health Questionnaire-8 (PHQ-8) for depression, and the Short Post-Traumatic Stress Disorder Rating Interview (SPRINT). Parents provided sociodemographics. Charts were reviewed for child characteristics. Results: One-hundred and fifty seven parents of 104 deceased children completed surveys at both time points. Mental health symptoms declined over time (mean (SD)): ICG (33.8 (15.4) vs. 30.5 (15.2), p < 0.001), PHQ-8 (9.0 (6.4) vs. 7.3 (5.8), p < 0.001), and SPRINT (14.1 (8.3) vs. 12.0 (8.2), p < 0.001). After controlling for 6-month scores, higher 13-month ICG was independently associated with sudden unexpected death; higher PHQ-8 with Black race, insecure attachment style, and sudden unexpected death; and higher SPRINT with having a high school level of education (compared to college degree or higher). Conclusion: Mental health symptoms improve among parents during the first 13 months after their child’s death; however, symptoms persist for many. Black parents and those whose children die suddenly may be high risk for poor adjustment during bereavement.

To describe health-related quality of life (HRQL) and functional outcomes in pediatric acute respiratory distress syndrome (ARDS) and to determine risk factors associated with poor outcome defined as death or severe reduction in HRQL at 28 days or ICU discharge.Prospective multisite cohort-outcome study conducted between 2019 and 2020.Eight academic PICUs in the United States.Children with ARDS based on standard criteria.Patient characteristics and illness severity were collected during PICU admission. Parent proxy-report measurements were obtained at baseline, day 28/ICU discharge, month 3, and month 9, utilizing Pediatric Quality of Life Inventory and Functional Status Scale (FSS). A composite outcome evaluated using univariate and multivariate analysis was death or severe reduction in HRQL (25% reduction in the Pediatric Quality of Life Inventory at day 28/ICU discharge.This study enrolled 122 patients with a median age of 3 years (interquartile range, 1-12 yr). Common etiologies of ARDS included pneumonia ( n = 63; 52%) and sepsis ( n = 27; 22%). At day 28/ICU discharge, half (50/95; 53%) of surviving patients with follow-up data reported a greater than 10% decrease in HRQL from baseline, and approximately one-third of participants ( n = 19/61; 31%) reported a greater than 10% decrease in HRQL at 9 months. Trends in FSS were similar. Of 104 patients with data, 47 patients (45%) died or reported a severe decrease of greater than 25% in HRQL at day 28/ICU discharge. Older age was associated with an increased risk of death or severe reduction in HRQL (odds ratio, 1.08; CI, 1.01-1.16).Children with ARDS are at risk for deterioration in HRQL and FSS that persists up to 9 months after ARDS. Almost half of children with ARDS experience a poor outcome including death or severe reduction in HRQL at day 28/ICU discharge.

PurposeFunctional outcomes have been proposed for assessing quality of pediatric trauma care. Outcomes assessments often rely on Abbreviated Injury Scale (AIS) severity scores to adjust for injury characteristics, but the relationship between AIS severity and functional impairment is unknown. This study's primary aim was to quantify functional impairment associated with increasing AIS severity scores within body regions. The secondary aim was to assess differences in impairment between body regions based on AIS severity.MethodsChildren with serious (AIS≥3) isolated body region injuries enrolled in a multicenter prospective study were analyzed. The primary outcome was functional status at discharge measured using the Functional Status Scale (FSS). Discharge FSS was compared (1) within each body region across increasing AIS severity scores, and (2) between body regions for injuries with matching AIS scores.ResultsThe study included 266 children, with 16% having abnormal FSS at discharge. Worse FSS was associated with increasing AIS severity only for spine injuries. Abnormal FSS was observed in a greater proportion of head injury patients with a severely impaired initial Glasgow Coma Scale (GCS) (GCS

Our objective was to associate characteristics of pediatric critical care medicine (PCCM) fellowship training programs with career outcomes of PCCM physicians, including research publication productivity and employment characteristics. This is a descriptive study using publicly available data from 2557 PCCM physicians from the National Provider Index registry. We analyzed data on a systematic sample of 690 PCCM physicians representing 62 fellowship programs. There was substantial diversity in the characteristics of fellowship training programs in terms of fellowship size, intensive care unit (ICU) bed numbers, age of program, location, research rank of affiliated medical school, and academic metrics based on publication productivity of their graduates standardized over time. The clinical and academic attributes of fellowship training programs were associated with publication success and characteristics of their graduates' employment hospital. Programs with greater publication rate per graduate had more ICU beds and were associated with higher ranked medical schools. At the physician level, training program attributes including larger size, older program, and higher academic metrics were associated with graduates with greater publication productivity. There were varied characteristics of current employment hospitals, with graduates from larger, more academic fellowship training programs more likely to work in larger pediatric intensive care units (24 [interquartile range, IQR: 16–35] vs. 19 [IQR: 12–24] beds; p

Our objective was to determine in children in the intensive care unit (ICU) the incidence of hyperchloremia (>110 mmol/L) and hypochloremia (

Objectives Therapeutic alliance is the collaborative bond that develops between patients/families and healthcare providers. Our objective is to determine the extent of therapeutic alliance bereaved parents perceive to have occurred with their child's physicians during their child's PICU stay, and associated factors. Design Multicenter observational study. Setting Eight children's hospitals affiliated with the Collaborative Pediatric Critical Care Research Network. Patients Parents greater than or equal to 18 years old whose child died in a PICU (including cardiac ICU). Interventions Bereaved parents completed the Human Connection Scale, a 16-item measure of therapeutic alliance, 6 months after their child's death. Human Connection Scale scores range from 16 to 64 with higher scores indicating greater alliance. Parents provided sociodemographic data, and medical records were reviewed for the child's clinical characteristics. Measurements and main results Two-hundred and thirty-three parents of 157 deceased children responded to the Human Connection Scale with greater than or equal to 80% item completion. Among parents, 146 (62.7%) were female, 155 (66.5%) were White and 46 (19.7%) were Black, 175 (75.1%) were married, and 209 (89.7%) had at least a high-school education. Among children, median age at the time of death was 5.9 years (interquartile range, 0.64-13.9 yr) and 114 (72.6%) died after limitation or withdrawal of life support. Mean Human Connection Scale score was 51.4 ± 11.1 for all parents, 52.6 ± 9.0 for White parents, and 47.0 ± 13.7 for Black parents. In multivariable modeling predicting Human Connection Scale scores, race was the only parent or child characteristic in the final model. Human Connection Scale scores were significantly different (-4.56; 95% CI, -8.53 to -0.6; p = 0.025) between the Black and White parents with items about trust, care, and honest communication showing the greatest mean difference. Conclusions Among parents bereaved in the PICU, therapeutic alliance with physicians is moderately high. Future research should identify strategies to strengthen therapeutic alliance with Black parents and examine the role of alliance on bereaved parents' health outcomes.

Objectives To identify trajectories and correlates of caregiver distress and family functioning in families of children who survived community-acquired septic shock. We hypothesized that: 1) a substantial subset of families would demonstrate trajectories of persistent elevated caregiver distress and impaired family functioning 12 months after hospitalization and 2) sociodemographic and clinical risk factors would be associated with trajectories of persistent distress and family dysfunction. Design Prospective cohort. Setting Fourteen PICUs in the United States. Patients Caregivers of 260 children who survived community-acquired septic shock. Interventions None. Measurements and main results Caregivers completed ratings of distress on the Brief Symptom Inventory and of family functioning on the Family Assessment Device at baseline, 1, 3, 6, and 12 months after hospitalization. Results from group-based trajectory modeling indicated that 67% of the current sample was characterized by persistent low caregiver distress, 26% by persistent moderate to high distress that remained stable across 12 months (high-risk caregiver distress group), and 8% by initial high distress followed by gradual recovery. Forty percent of the sample was characterized by stable high family functioning, 15% by persistent high dysfunction across 12 months (high-risk family functioning group), 12% by gradually improving functioning, and 32% by deteriorating function over time. Independently of age, child race was associated with membership in the high-risk caregiver distress group (non-white/Hispanic; effect size, -0.12; p = 0.010). There were no significant sociodemographic or clinical correlates of the high-risk family functioning group in multivariable analyses. Conclusions Although the majority of families whose children survived community-acquired septic shock were characterized by resilience, a subgroup demonstrated trajectories of persistently elevated distress and family dysfunction during the 12 months after hospitalization. Results suggest a need for family-based psychosocial screening after pediatric septic shock to identify and support at-risk families.

OBJECTIVE: To describe at the individual patient level the pathophysiologic processes contributing to morbidity and mortality in pediatric intensive care units (PICUs) and therapeutic additions and advances that could potentially prevent or reduce morbidity and mortality. DESIGN: Qualitative content analysis of intensivists’ conclusions on pathophysiologic processes and needed therapeutic advances formulated by structured medical record review. SETTING: Eight children’s hospitals affiliated with the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS: A randomly selected cohort of critically ill children with a new functional morbidity or mortality at hospital discharge. New morbidity was assessed using the Functional Status Scale and defined as worsening by two or more points in a single domain from pre-illness baseline. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 292 children, 175 (59.9%) had a new morbidity and 117 (40.1%) died. The most common pathophysiology was impaired substrate delivery (n=158, 54.1%) manifesting as global or regional hypoxia or ischemia due to low cardiac output or cardiac arrest. Other frequent pathophysiologies were inflammation (n=104, 35.6%) related to sepsis, respiratory failure, acute respiratory distress syndrome or multiple organ dysfunction; and direct tissue injury (n=64, 21.9%) including brain and spinal cord trauma. Chronic conditions were often noted (n=156, 53.4%) as contributing to adverse outcomes. Drug therapies (n=149, 51.0%) including chemotherapy, inotropes, vasoactive agents and sedatives were the most frequently proposed needed therapeutic advances. Other frequently proposed therapies included cell regeneration (n=115, 39.4%) mainly for treatment of neuronal injury, and improved immune and inflammatory modulation (n=79, 27.1%). CONCLUSIONS: Low cardiac output and cardiac arrest, inflammation-related organ failures, and central nervous system trauma were the most common pathophysiologies leading to morbidity and mortality in PICUs. A research agenda focused on better understanding and treatment of these conditions may have high potential to directly impact patient outcomes.

Objectives Developing effective therapies to reduce morbidity and mortality requires knowing the responsible pathophysiologies and the therapeutic advances that are likely to be impactful. Our objective was to determine at the individual patient level the important pathophysiological processes and needed therapeutic additions and advances that could prevent or ameliorate morbidities and mortalities. Design Structured chart review by pediatric intensivists of PICU children discharged with significant new morbidity or mortality to determine the pathophysiologies responsible for poor outcomes and needed therapeutic advances. Setting Multicenter study (eight sites) from the Collaborative Pediatric Critical Care Research Network of general and cardiac PICUs. Patients First PICU admission of patients from December 2011 to April 2013. Interventions None. Measurements and main results Two-hundred ninety-two patients were randomly selected from 681 patients discharged with significant new morbidity or mortality. The median age was 2.4 years, 233 (79.8%) were in medical/surgical ICUs, 59 (20.2%) were in cardiac ICUs. Sixty-five (22.3%) were surgical admissions. The outcomes included 117 deaths and 175 significant new morbidities. The most common pathophysiologies contributing to the poor outcomes were impaired substrate delivery (n = 158, 54.1%) and inflammation (n = 104, 35.6%). There were no strong correlations between the pathophysiologies and no remarkable clusters among them. The most common therapeutic needs involved new drugs (n = 149, 51.0%), cell regeneration (n = 115, 39.4%), and immune and inflammatory modulation (n = 79, 27.1%). As with the pathophysiologies, there was a lack of strong correlations or meaningful clusters in the suggested therapeutic needs. Conclusions There was no single dominant pathophysiology or cluster of pathophysiologies responsible for poor pediatric critical care outcomes. Therapeutic needs often involved therapies that are not close to implementation such as cell regeneration, improved organ transplant, improved extracorporeal support and artificial organs, and improved drugs.

AIM: The mathematical method used to calculate chest compression (CC) rate during cardiopulmonary resuscitation varies in the literature and across device manufacturers. The objective of this study was to determine the variability in calculated CC rates by applying four published methods to the same dataset. METHODS: This study was a secondary investigation of the first 200 pediatric cardiac arrest events with invasive arterial line waveform data in the ICU-RESUScitation Project (NCT02837497). Instantaneous CC rates were calculated during periods of uninterrupted CCs. The defined minimum interruption length affects rate calculation (e.g., if an interruption is defined as a break in CCs ≥ 2 seconds, the lowest possible calculated rate is 30 CCs/min). Average rates were calculated by four methods: 1) rate with an interruption defined as ≥ 1 second; 2) interruption ≥ 2 seconds; 3) interruption ≥ 3 seconds; 4) method #3 excluding top and bottom quartiles of calculated rates. American Heart Association Guideline-compliant rate was defined as 100–120 CCs/min. A clinically important change was defined as ± 5 CCs/min. The percentage of events and epochs (30 second periods) that changed Guideline-compliant status was calculated. RESULTS: Across calculation methods, mean CC rates (118.7 – 119.5/min) were similar. Comparing all methods, 14 events (7%) and 114 epochs (6%) changed Guideline-compliant status. CONCLUSION: Using four published methods for calculating CC rate, average rates were similar, but 7% of events changed Guideline-compliant status. These data suggest that a uniform calculation method (interruption ≥ 1 second) should be adopted to decrease variability in resuscitation science.

Risk factors for mortality in children with refractory pediatric septic shock who are supported with extracorporeal life support (ECLS) are largely unknown. Therefore, we performed univariable and multivariable analyses to determine risk factors for mortality among children (

Objectives To characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes. Design An observational cohort study. Setting Eight sites of the Collaborative Pediatric Critical Care Research Network. Patients One hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication. Measurements and main results Clinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity. Conclusions Clinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.

Objectives To describe the pharmaceutical management of sedation, analgesia, and neuromuscular blockade medications administered to children in ICUs. Design A retrospective analysis using data extracted from the national database Health Facts. Setting One hundred sixty-one ICUs in the United States with pediatric admissions. Patients Children in ICUs receiving medications from 2009 to 2016. Exposure/intervention Frequency and duration of administration of sedation, analgesia, and neuromuscular blockade medications. Measurements and main results Of 66,443 patients with a median age of 1.3 years (interquartile range, 0-14.5), 63.3% (n = 42,070) received nonopioid analgesic, opioid analgesic, sedative, and/or neuromuscular blockade medications consisting of 83 different agents. Opioid and nonopioid analgesics were dispensed to 58.4% (n = 38,776), of which nonopioid analgesics were prescribed to 67.4% (n = 26,149). Median duration of opioid analgesic administration was 32 hours (interquartile range, 7-92). Sedatives were dispensed to 39.8% (n = 26,441) for a median duration of 23 hours (interquartile range, 3-84), of which benzodiazepines were most common (73.4%; n = 19,426). Neuromuscular-blocking agents were dispensed to 17.3% (n = 11,517) for a median duration of 2 hours (interquartile range, 1-15). Younger age was associated with longer durations in all medication classes. A greater proportion of operative patients received these medication classes for a longer duration than nonoperative patients. A greater proportion of patients with musculoskeletal and hematologic/oncologic diseases received these medication classes. Conclusions Analgesic, sedative, and neuromuscular-blocking medications were prescribed to 63.3% of children in ICUs. The durations of opioid analgesic and sedative medication administration found in this study can be associated with known complications, including tolerance and withdrawal. Several medications dispensed to pediatric patients in this analysis are in conflict with Food and Drug Administration warnings, suggesting that there is potential risk in current sedation and analgesia practice that could be reduced with practice changes to improve efficacy and minimize risks.

BACKGROUND AND OBJECTIVES: Chart reviews are frequently used for research, care assessments, and quality improvement activities despite an absence of data on reliability and validity. We aim to describe a structured chart review methodology and to establish its validity and reliability. METHODS: A generalizable structured chart review methodology was designed to evaluate causes of morbidity or mortality and to identify potential therapeutic advances. The review process consisted of a 2-tiered approach with a primary review completed by a site physician and a short secondary review completed by a central physician. A total of 327 randomly selected cases of known mortality or new morbidities were reviewed. Validity was assessed by using postreview surveys with a Likert scale. Reliability was assessed by percent agreement and interrater reliability. RESULTS: The primary reviewers agreed or strongly agreed in 94.9% of reviews that the information to form a conclusion about pathophysiological processes and therapeutic advances could be adequately found. They agreed or strongly agreed in 93.2% of the reviews that conclusions were easy to make, and confidence in the process was 94.2%. Secondary reviewers made modifications to 36.6% of cases. Duplicate reviews (n = 41) revealed excellent percent agreement for the causes (80.5%–100%) and therapeutic advances (68.3%–100%). κ statistics were strong for the pathophysiological categories but weaker for the therapeutic categories. CONCLUSIONS: A structured chart review by knowledgeable primary reviewers, followed by a brief secondary review, can be valid and reliable.

To determine associations between anticoagulation practices and bleeding and thrombosis during pediatric extracorporeal membrane oxygenation (ECMO), we performed a secondary analysis of prospectively collected data which included 481 children (80 ml/kg on any day, pulmonary hemorrhage, or intracranial bleeding, Thrombotic events included pulmonary emboli, intracranial clot, limb ischemia, cardiac clot, and arterial cannula or entire circuit change. Bleeding occurred in 42% of patients. Five percent of subjects thrombosed, of which 89% also bled. Daily bleeding odds were independently associated with day prior activated clotting time (ACT) (OR 1.03, 95% CI= 1.00, 1.05, p=0.047) and fibrinogen levels (OR 0.90, 95% CI 0.84, 0.96, p

Background: Although bereaved parents suffer greatly, some may experience positive change referred to as post-traumatic growth. Objective: Explore the extent to which parents perceive post-traumatic growth after their child's death in a pediatric intensive care unit (PICU), and associated factors. Design: Longitudinal parent survey conducted 6 and 13 months after a child's death. Surveys included the Post-traumatic Growth Inventory-Short Form (PTGI-SF), a 10-item measure with range of 0–50 where higher scores indicate more post-traumatic growth. Surveys also included the Inventory of Complicated Grief (ICG), the Patient Health Questionnaire-8 (PHQ-8) for depression, the Short Post-Traumatic Stress Disorder Rating Interview (SPRINT), a single item on perceived overall health, and sociodemographics. Setting/Subjects: One hundred fifty-seven parents of 104 children who died in 1 of 8 PICUs affiliated with the U.S. Collaborative Pediatric Critical Care Research Network. Results: Of participating parents, 62.4% were female, 71.6% White, 82.7% married, and 89.2% had at least a high school education. Mean PTGI-SF scores were 27.5 ± 12.52 (range 5–50) at 6 months and 28.6 ± 11.52 (range 2–49) at 13 months (p = 0.181). On multivariate modeling, higher education (compared with those not completing high school) and higher 6-month ICG scores (reflecting more complicated grief symptoms) were associated with lower 13-month PTGI-SF scores (p = 0.005 and 0.033, respectively). Conclusion: Parents bereaved by their child's PICU death perceive a moderate degree of post-traumatic growth in the first 13 months after the death however variability is wide. Education level and complicated grief symptoms may influence parents' perception of post-traumatic growth.

BACKGROUND: Little is known about the epidemiology of and outcomes related to red blood cell (RBC) transfusion in septic children across multiple centers. We performed propensity-adjusted secondary analyses of the Biomarker Phenotyping of Pediatric Sepsis and Multiple Organ Failure (PHENOMS) study to test the hypothesis that early RBC transfusion is associated with fewer organ failure-free days in pediatric severe sepsis. METHODS: 401 children were enrolled in the parent study. Children were excluded from these analyses if they received extracorporeal membrane oxygenation (n = 22) or died (n = 1) before sepsis day 2. Propensity-adjusted analyses compared children who received RBC transfusion on or before sepsis day 2 (early RBC transfusion) with those who did not. Logistic regression was used to model the propensity to receive early RBC transfusion. A weighted cohort was constructed using stabilized inverse probability of treatment weights. Variables in the weighted cohort with absolute standardized differences > 0.15 were added to final multivariable models. RESULTS: 50% of children received at least one RBC transfusion. The majority (68%) of first transfusions were on or before sepsis day 2. Early RBC transfusion was not independently associated with organ failure-free (−0.34 [95%CI: − 2, 1.3] days) or PICU-free days (−0.63 [−2.3, 1.1]), but was associated with the secondary outcome of higher mortality (aOR 2.9 [1.1, 7.9]). CONCLUSIONS: RBC transfusion is common in pediatric severe sepsis and may be associated with adverse outcomes. Future studies are needed to clarify these associations, to understand patient-specific transfusion risks, and to develop more precise transfusion strategies.

Key Points Question Does intravenous (IV) acetaminophen administered prior to IV opioids reduce the total duration of IV opioids administered during a patient’s inpatient hospitalization? Findings In this comparative effectiveness research study including 893 293 hospitalized children, administration of IV acetaminophen prior to IV opioids was associated with a significant 15.5% reduction in total IV opioid duration when compared with administration of IV opioids alone. Meaning The results of this study suggest that IV acetaminophen administered prior to IV opioids should be considered in multimodal pain regimens because it may potentially reduce the total duration of IV opioids administered to hospitalized children., This comparative effectiveness research study evaluates whether receipt of intravenous acetaminophen before receipt of intravenous opioid is associated with a reduction in intravenous opioid duration., Importance Adoption of multimodal pain regimens that incorporate nonopioid analgesic medications to reduce inpatient opioid administration can prevent serious opioid-related adverse effects in children, including tolerance, withdrawal, delirium, and respiratory depression. Intravenous (IV) acetaminophen is in widespread pediatric use; however, its effectiveness as an opioid-sparing agent has not been evaluated in general pediatric inpatients. Objective To determine if IV acetaminophen administered prior to IV opioids is associated with a reduction in the total duration of IV opioids administered compared with IV opioids administered without IV acetaminophen in general pediatric inpatients. Design, Setting, and Participants This comparative effectiveness research study included data on pediatric inpatients from 274 US hospitals between January 2011 and June 2016 collected from a national database. Outcomes were compared with a propensity score–matched analysis of pediatric inpatients administered IV opioids without IV acetaminophen (control) and those administered IV acetaminophen prior to IV opioids (intervention). Data were analyzed from January 2020 through October 2021. Exposures Patients in the intervention group received IV acetaminophen prior to IV opioids. Patients in the control group received IV opioids without IV acetaminophen. Main Outcomes and Measures Total duration of all IV opioids administered during a patient’s hospitalization. Results Of 893 293 pediatric inpatients, a total of 104 579 were included in analysis (median [IQR] age, 1.3 [0-14.7] years; 59 806 [57.2%] female; 21 485 [21.5%] African American, 56 309 [53.8%] White), of whom 18 197 (2.0%) received IV acetaminophen, and 287 504 (34.0%) received IV opioids. After applying exclusion criteria, among patients who received IV acetaminophen, 1739 (10.8%) received IV acetaminophen prior to IV opioids within a median (IQR) treatment time of 1.5 (0.02-7.3) hours. After propensity score matching produced comparable groups in the control and intervention groups (with 839 patients in each group), the multivariable model estimated a 15.5% shorter duration of IV opioid use in the intervention group, with an absolute IV opioid reduction of 7.5 hours (95% CI, 0.7-15.8 hours). Conclusions and Relevance In this comparative effectiveness study, IV acetaminophen administered prior to IV opioids was associated with a reduction in IV opioid duration by 15.5%. Multimodal pain regimens that use IV acetaminophen prior to IV opioids could reduce IV opioid duration.

ObjectiveThrombotic microangiopathy induced Thrombocytopenia Associated Multiple Organ Failure and hyperinflammatory Macrophage Activation Syndrome are important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. Our objective is to derive computable 24-hour sepsis phenotypes to facilitate enrollment in early precise anti-inflammatory trials targeting mortality from these conditions.DesignMachine learning analysis using consensus k-means clustering.SettingNine pediatric intensive care units.Patients404 children with severe sepsis.Interventions24-hour computable phenotypes derived using 25 bedside variables including C-reactive protein and ferritin.Measurements and Main ResultsFour computable phenotypes (PedSep-A, B, C, and D) are derived. Compared to the overall population mean, PedSep-A has the least inflammation (median C-reactive protein 7.3 mg/dL, ferritin 125 ng/mL), younger age, less chronic illness, and more respiratory failure (n = 135; 2% mortality); PedSep-B (median C-reactive protein 13.2 mg/dL, ferritin 225 ng/ mL) has organ failure with intubated respiratory failure, shock, and Glasgow Coma Scale score < 7 (n = 102, 12% mortality); PedSep-C (median C-reactive protein 15.2 mg/dL, ferritin 405 ng/mL) has elevated ferritin, lymphopenia, more shock, more hepatic failure and less respiratory failure (n = 110; mortality 10%); and, PedSep D (median C-reactive protein 13.1 mg/dL ferritin 610 ng/mL), has hyperferritinemic, thrombocytopenic multiple organ failure with more cardiovascular, respiratory, hepatic, renal, hematologic, and neurologic system failures (n = 56, 34% mortality). PedSep-D has highest likelihood of Thrombocytopenia Associated Multiple Organ Failure (Adj OR 47.51 95% CI [18.83-136.83], p < 0.0001) and Macrophage Activation Syndrome (Adj OR 38.63 95% CI [13.26-137.75], p CONCLUSIONS AND RELEVANCEMachine learning identifies four computable phenotypes (www.pedsepsis.pitt.edu). Membership in PedSep-D appears optimal for enrollment in early anti-inflammatory trials targeting Thrombocytopenia Associated Multiple Organ Failure and Macrophage Activation Syndrome.Author’s CommentQuestionCan machine learning methods derive 24-hour computable pediatric sepsis phenotypes that facilitate early identification of patients for enrollment in precise anti-inflammatory therapy trials?FindingsFour distinct phenotypes (PedSep-A, B, C, and D) were derived by assessing 25 bedside clinical variables in 404 children with sepsis. PedSep-D patients had a thrombotic microangiopathy and hyperinflammatory macrophage activation biomarker response, and improved survival odds associated with combined methylprednisolone plus intravenous immunoglobulin therapy.MeaningFour novel computable 24-hour phenotypes are identifiable (www.pedsepsis.pitt.edu) that could potentially facilitate enrollment in early precise anti-inflammatory trials targeting thrombotic microangiopathy and macrophage activation in pediatric sepsis.

OBJECTIVES: Multisystem inflammatory syndrome in children is a newly defined complication of severe acute respiratory syndrome coronavirus 2 infection that can result in cardiogenic shock in the pediatric population. Early detection of cardiac dysfunction is imperative in directing therapy and identifying patients at highest risk for deterioration. This study compares the strengths of conventional and strain echocardiography in identifying cardiac dysfunction in critically ill children with multisystem inflammatory syndrome in children and their association with ICU therapeutic needs and clinical outcomes. DESIGN: Retrospective, observational cohort study. SETTING: A large, quaternary care PICU. PATIENTS: Sixty-five pediatric patients admitted to the PICU with the diagnosis of multisystem inflammatory syndrome in children from March 2020 to March 2021. INTERVENTIONS: Global longitudinal strain four chamber was measured retrospectively by strain echocardiography and compared with conventional echocardiography. Cardiac dysfunction was defined by left ventricular ejection fraction less than 55% and global longitudinal strain four chamber greater than or equal to -17.2%. Clinical variables examined included cardiac biomarkers, immune therapies, and ICU interventions and outcomes. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients (37%) had abnormal left ventricular ejection fraction and 56 (86%) had abnormal global longitudinal strain four chamber. Between patients with normal and abnormal left ventricular ejection fraction, we failed to identify a difference in cardiac biomarker levels, vasoactive use, respiratory support needs, or ICU length of stay. Global longitudinal strain four chamber was associated with maximum cardiac biomarker levels. Abnormal global longitudinal strain four chamber was associated with greater odds of any vasoactive use (odds ratio, 5.8; 95% CI, 1.3-25.3; z-statistic, 2.3; p = 0.021). The number of days of vasoactive infusion was correlated with global longitudinal strain four chamber (r = 0.400; 95% CI, 2.4-3.9; p < 0.001). Children with abnormal strain had longer ICU length of stay (4.5 d vs 2 d; p = 0.014). CONCLUSIONS: Our findings suggest strain echocardiography can detect abnormalities in cardiac function in multisystem inflammatory syndrome in children patients unrecognized by conventional echocardiography. These abnormalities are associated with increased use of intensive care therapies. Evaluation of these patients with strain echocardiography may better identify those with myocardial dysfunction and need for more intensive therapy.

Supplemental Digital Content is available in the text., OBJECTIVES: Develop and compare separate prediction models for ICU and non-ICU care for hospitalized children in four future time periods (6–12, 12–18, 18–24, and 24–30 hr) and assess these models in an independent cohort and simulated children’s hospital. DESIGN: Predictive modeling used cohorts from the Health Facts database (Cerner Corporation, Kansas City, MO). SETTING: Children hospitalized in ICUs. PATIENTS: Children with greater than or equal to one ICU admission (n = 20,014) and randomly selected routine care children without ICU admission (n = 20,130) from 2009 to 2016 were used for model development and validation. An independent 2017–2018 cohort consisted of 80,089 children. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Initially, we undersampled non-ICU patients for development and comparison of the models. We randomly assigned 64% of patients for training, 8% for validation, and 28% for testing in both clinical groups. Two additional validation cohorts were tested: a simulated children’s hospitals and the 2017–2018 cohort. The main outcome was ICU care or non-ICU care in four future time periods based on physiology, therapy, and care intensity. Four independent, sequential, and fully connected neural networks were calibrated to risk of ICU care at each time period. Performance for all models in the test sample were comparable including sensitivity greater than or equal to 0.727, specificity greater than or equal to 0.885, accuracy greater than 0.850, area under the receiver operating characteristic curves greater than or equal to 0.917, and all had excellent calibration (all R2s > 0.98). Model performance in the 2017–2018 cohort was sensitivity greater than or equal to 0.545, specificity greater than or equal to 0.972, accuracy greater than or equal to 0.921, area under the receiver operating characteristic curves greater than or equal to 0.946, and R2s greater than or equal to 0.979. Performance metrics were comparable for the simulated children’s hospital and for hospitals stratified by teaching status, bed numbers, and geographic location. CONCLUSIONS: Machine learning models using physiology, therapy, and care intensity predicting future care needs had promising performance metrics. Notably, performance metrics were similar as the prediction time periods increased from 6–12 hours to 24–30 hours.

Aim In-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0–20 min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge. Methods This is a secondary analysis of the Pediatric Intensive Care Quality of CPR (PICqCPR) study of invasively measured blood pressures during intensive care unit CPR. Patients were eligible if they achieved ROSC and had at least one invasively measured blood pressure within the first 20 min following ROSC. Post-ROSC blood pressures were normalized for age, sex and height. “Immediate hypertension” was defined as at least one systolic or diastolic blood pressure >90th percentile. The primary outcome was survival to hospital discharge. Results Of 102 children, 70 (68.6%) had at least one episode of immediate post-CPR diastolic hypertension. After controlling for pre-existing hypotension, duration of CPR, calcium administration, and first documented rhythm, patients with immediate post-CPR diastolic hypertension were more likely to survive to hospital discharge (79.3% vs. 54.5%; adjusted OR = 2.93; 95%CI, 1.16–7.69). Conclusions In this post hoc secondary analysis of the PICqCPR study, 68.6% of subjects had diastolic hypertension within 20 min of ROSC. Immediate post-ROSC hypertension was associated with increased odds of survival to discharge, even after adjusting for covariates of interest.

Because pediatric trauma-related mortality continues to decline, metrics assessing morbidity are needed to evaluate the impact of treatment after injury. Based on its value for assessing children with traumatic brain injuries and other critical illnesses, Functional Status Scale (FSS), a tool that measures function in six domains (communication, feeding, mental, motor, sensory, and respiratory), was evaluated as an outcome measure for the overall population of injured children.Children with at least one injury (Abbreviated Injury Scale [AIS] severity ≥1) surviving to discharge between December 2011 and April 2013 were identified in a previous study of intensive care unit admissions. Morbidity was defined as additional morbidity in any domain (domain FSS change ≥2 or 'new domain morbidity') and additional overall morbidity (total FSS change ≥3) between preinjury status and discharge. Associations between injury profiles and the development of morbidity were analyzed.We identified 553 injured children, with a mean of 2.0 ± 1.9 injuries. New domain and overall morbidity were observed in 17.0% and 11.0% of patients, respectively. New domain morbidity was associated with an increasing number of body regions with an injury with AIS ≥ 2 (p0.001), with severe (AIS ≥ 4) head (p = 0.04) and spine (p = 0.01) injuries and with at moderately severe (AIS ≥ 2) lower extremity injuries (p = 0.01). New domain morbidity was more common among patients with severe spine and lower extremity injuries (55.6% and 48.7%, respectively), with greatest impact in the motor domain (55.6% and 43.6%, respectively). New domain morbidity was associated with increasing injury severity score, number of moderately severe injuries and number of body regions with more than a moderately severe injury (p0.001 for all).Higher morbidity measured by the FSS is associated with increasing injury severity. These findings support the use of the FSS as a metric for assessing outcome after pediatric injury.Prognostic/Epidemiologic, level III.

BACKGROUND Children with abusive injuries have worse mortality, length-of-stay, complications, and healthcare costs compared to those sustaining an accidental injury. Long-term functional impairment is common in children with abusive head trauma but has not been examined in a cohort with heterogeneous body region injuries. OBJECTIVE To assess for an independent association between child physical abuse and functional impairment at discharge and six-month follow-up. PARTICIPANTS AND SETTING Seriously injured children (

Background Disability and impaired health-related quality of life can persist for months among injured children. Previous studies of long-term outcomes have focused mainly on children with specific injury types rather than those with multiple injured body regions. This study's objective was to determine the long-term functional status and health-related quality of life after serious pediatric injury, and to evaluate the associations of these outcomes with features available at hospital discharge. Study Design We conducted a prospective observational study at 7 Level I pediatric trauma centers of children treated for at least 1 serious (Abbreviated Injury Scale severity 3 or higher) injury. Patients were sampled to increase the representation of less frequently injured body regions and multiple injured body regions. Six-month functional status was measured using the Functional Status Scale (FSS) and health-related quality of life using the Pediatric Quality of Life Inventory. Results Among 323 injured children with complete discharge and follow-up assessments, 6-month FSS score was abnormal in 33 patients (10.2%)—16 with persistent impairments and 17 previously normal at discharge. Increasing levels of impaired discharge FSS score were associated with impaired FSS and lower Pediatric Quality of Life Inventory scores at 6-month follow-up. Additional factors on multivariable analysis associated with 6-month FSS impairment included older age, penetrating injury type, severe head injuries, and spine injuries, and included older age for lower 6-month Pediatric Quality of Life Inventory scores. Conclusions Older age and discharge functional status are associated with long-term impairment of functional status and health-related quality of life. Although most seriously injured children return to normal, ongoing disability and reduced health-related quality of life remained 6 months after injury. Our findings support long-term assessments as standard practice for evaluating the health impacts of serious pediatric injury.