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OBJECTIVES: Children who suffer traumatic brain injury (TBI) are at high risk of morbidity and mortality. We hypothesized that in patients with TBI, the abusive head trauma (AHT) mechanism vs. accidental TBI (aTBI) would be associated with higher frequency of new functional impairment between baseline and later follow-up. DESIGN: Retrospective single center cohort study. SETTING AND PATIENTS: Children younger than 3 years old admitted with TBI to the PICU at a level 1 trauma center between 2014 and 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, TBI mechanism, and Functional Status Scale (FSS) scores at baseline, hospital discharge, short-term (median, 10 mo [interquartile range 3-12 mo]), and long-term (median, 4 yr [3-6 yr]) postdischarge were abstracted from the electronic health record. New impairment was defined as an increase in FSS greater than 1 from baseline. Patients who died were assigned the highest score (30). Multivariable logistic regression was performed to determine the association between TBI mechanism with new impairment. Over 6 years, there were 460 TBI children (170 AHT, 290 aTBI), of which 13 with AHT and four with aTBI died. Frequency of new impairment by follow-up interval, in AHT vs. aTBI patients, were as follows: hospital discharge (42/157 [27%] vs. 27/286 [9%]; p < 0.001), short-term (42/153 [27%] vs. 26/259 [10%]; p < 0.001), and long-term (32/114 [28%] vs. 18/178 [10%]; p < 0.001). Sensory, communication, and motor domains were worse in AHT patients at the short- and long-term timepoint. On multivariable analysis, AHT mechanism was associated with greater odds (odds ratio [95% CI]) of poor outcome (death and new impairment) at hospital discharge (4.4 [2.2-8.9]), short-term (2.7 [1.5-4.9]), and long-term timepoints (2.4 [1.2-4.8]; p < 0.05). CONCLUSIONS: In patients younger than 3 years old admitted to the PICU after TBI, the AHT mechanism-vs. aTBI-is associated with greater odds of poor outcome in the follow-up period through to ~5 years postdischarge. New impairment occurred in multiple domains and only AHT patients further declined in FSS over time.

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OBJECTIVES: Acute disorders of consciousness (DoC) in pediatric severe sepsis are associated with increased risk of morbidity and mortality. We sought to examine the frequency of and factors associated with DoC in children with sepsis-induced organ failure. DESIGN: Secondary analysis of the multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS). SETTING: Nine tertiary care PICUs in the United States. PATIENTS: Children less than 18 years old admitted to a PICU with severe sepsis and at least one organ failure during a PICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was frequency of DoC, defined as Glasgow Coma Scale (GCS) less than 12 in the absence of sedatives during an ICU stay, among children with severe sepsis and the following: single organ failure, nonphenotypeable multiple organ failure (MOF), MOF with one of the PHENOMS phenotypes (immunoparalysis-associated MOF [IPMOF], sequential liver failure-associated MOF, thrombocytopenia-associated MOF), or MOF with multiple phenotypes. A multivariable logistic regression analysis was performed to evaluate the association between clinical variables and organ failure groups with DoC. Of 401 children studied, 71 (18%) presented with DoC. Children presenting with DoC were older (median 8 vs 5 yr; p = 0.023), had increased hospital mortality (21% vs 10%; p = 0.011), and more frequently presented with both any MOF (93% vs 71%; p < 0.001) and macrophage activation syndrome (14% vs 4%; p = 0.004). Among children with any MOF, those presenting with DoC most frequently had nonphenotypeable MOF and IPMOF (52% and 34%, respectively). In the multivariable analysis, older age (odds ratio, 1.07; 95% CI, 1.01-1.12) and any MOF (3.22 [1.19-8.70]) were associated with DoC. CONCLUSIONS: One of every five children with severe sepsis and organ failure experienced acute DoC during their PICU stay. Preliminary findings suggest the need for prospective evaluation of DoC in children with sepsis and MOF.

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OBJECTIVES: 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. DESIGN: Prospective observational study. SETTING: Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020. PATIENTS: Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

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OBJECTIVES: The 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. DESIGN: Multicenter 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). SETTING: Data source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial. PATIENTS: Children (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 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). CONCLUSIONS: Using 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.

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OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

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BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

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OBJECTIVES: Neurologic complications, consisting of the acute development of a neurologic disorder, that is, not present at admission but develops during the course of illness, can be difficult to detect in the PICU due to sedation, neuromuscular blockade, and young age. We evaluated the direct relationships of serum biomarkers and clinical variables to the development of neurologic complications. Analysis was performed using mixed graphical models, a machine learning approach that allows inference of cause-effect associations from continuous and discrete data. DESIGN: Secondary analysis of a previous prospective observational study. SETTING: PICU, single quaternary-care center. PATIENTS: Individuals admitted to the PICU, younger than18 years old, with intravascular access via an indwelling catheter. INTERVENTIONS: None. MEASUREMENTS: About 101 patients were included in this analysis. Serum (days 1-7) was analyzed for glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and alpha-II spectrin breakdown product 150 utilizing enzyme-linked immunosorbent assays. Serum levels of neuron-specific enolase, myelin basic protein, and S100 calcium binding protein B used in these models were reported previously. Demographic data, use of selected clinical therapies, lengths of stay, and ancillary neurologic testing (head CT, brain MRI, and electroencephalogram) results were recorded. The Mixed Graphical Model-Fast-Causal Inference-Maximum algorithm was applied to the dataset. MAIN RESULTS: About 13 of 101 patients developed a neurologic complication during their critical illness. The mixed graphical model identified peak levels of the neuronal biomarker neuron-specific enolase and ubiquitin C-terminal hydrolase-L1, and the astrocyte biomarker glial fibrillary acidic protein to be the direct causal determinants for the development of a neurologic complication; in contrast, clinical variables including age, sex, length of stay, and primary neurologic diagnosis were not direct causal determinants. CONCLUSIONS: Graphical models that include biomarkers in addition to clinical data are promising methods to evaluate direct relationships in the development of neurologic complications in critically ill children. Future work is required to validate and refine these models further, to determine if they can be used to predict which patients are at risk for/or with early neurologic complications.

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OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

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OBJECTIVES: Assessing outcomes after pediatric critical illness is imperative to evaluate practice and improve recovery of patients and their families. We conducted a scoping review of the literature to identify domains and instruments previously used to evaluate these outcomes. DESIGN: Scoping review. SETTING: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials Registry for studies evaluating pediatric critical care survivors or their families published between 1970 and 2017. We identified articles using key words related to pediatric critical illness and outcome domains. We excluded articles if the majority of patients were greater than 18 years old or less than 1 month old, mortality was the sole outcome, or only instrument psychometrics or procedural outcomes were reported. We used dual review for article selection and data extraction and categorized outcomes by domain (overall health, emotional, physical, cognitive, health-related quality of life, social, family). SUBJECTS: Manuscripts evaluating outcomes after pediatric critical illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 60,349 citations, 407 articles met inclusion criteria; 87% were published after 2000. Study designs included observational (85%), interventional (7%), qualitative (5%), and mixed methods (3%). Populations most frequently evaluated were traumatic brain injury (n = 96), general pediatric critical illness (n = 87), and congenital heart disease (n = 72). Family members were evaluated in 74 studies (18%). Studies used a median of 2 instruments (interquartile range 1-4 instruments) and evaluated a median of 2 domains (interquartile range 2-3 domains). Social (n = 223), cognitive (n = 183), and overall health (n = 161) domains were most frequently studied. Across studies, 366 unique instruments were used, most frequently the Wechsler and Glasgow Outcome Scales. Individual domains were evaluated using a median of 77 instruments (interquartile range 39-87 instruments). CONCLUSIONS: A comprehensive, generalizable understanding of outcomes after pediatric critical illness is limited by heterogeneity in methodology, populations, domains, and instruments. Developing assessment standards may improve understanding of postdischarge outcomes and support development of interventions after pediatric critical illness.

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OBJECTIVES: To evaluate the incidence of anemia in patients with abusive head trauma (AHT), noninflicted traumatic brain injury (TBI), and physical abuse without AHT and the effect of anemia on outcome. STUDY DESIGN: In a retrospective, single-center cohort study, we included children under the age of 3 years diagnosed with either AHT (n = 75), noninflicted TBI (n = 77), or physical abuse without AHT (n = 60) between January 1, 2014, and December 31, 2016. Neuroimaging was prospectively analyzed by pediatric neuroradiologists. Primary outcome was anemia at hospital presentation. Secondary outcomes included unfavorable outcome at hospital discharge, defined as a Glasgow Outcome Scale between 1 and 3, and intracranial hemorrhage (ICH) volume. RESULTS: Patients with AHT had a higher rate of anemia on presentation (47.3%) vs noninflicted TBI (15.6%) and physical abuse without AHT (10%) (P < .001). Patients with AHT had larger ICH volumes (33.3 mL [10.1-76.4 mL] vs 1.5 mL [0.6-5.2 mL] ; P < .001) and greater ICH/total brain volume percentages than patients with noninflicted TBI (4.6% [1.4-8.2 %] vs 0.2% [0.1-0.7%]; P < .001). Anemia was associated with AHT (OR, 4.7; 95% CI, 2.2-10.2) and larger ICH/total brain volume percentage (OR, 1.1; 95% CI, 1.1-1.2) in univariate analysis. Unfavorable outcome at hospital discharge was associated with anemia (OR, 4.4; 95% CI, 1.6-12.6) in univariate analysis, but not after controlling for covariates. CONCLUSIONS: Patients with AHT were more likely to present to the hospital with anemia and increased traumatic ICH volume than patients with noninflicted TBI or physical abuse without AHT. Children with anemia and AHT may be at increased risk for an unfavorable outcome.

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OBJECTIVES: Develop and test the performance of electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV and electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 scores. DESIGN: Retrospective, single-center cohort derived from structured electronic health record data. SETTING: Large, quaternary PICU at a freestanding, university-affiliated children's hospital. PATIENTS: All encounters with a PICU admission between January 1, 2009, and December 31, 2017, identified using electronic definitions of inpatient encounter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome was predictive validity of each score for hospital mortality, assessed as model discrimination and calibration. Discrimination was examined with the area under the receiver operating characteristics curve and the area under the precision-recall curve. Calibration was assessed with the Hosmer-Lemeshow goodness of fit test and calculation of a standardized mortality ratio. Models were recalibrated with new regression coefficients in a training subset of 75% of encounters selected randomly from all years of the cohort and the calibrated models were tested in the remaining 25% of the cohort. Content validity was assessed by examining correlation between electronic versions of the scores and prospectively calculated data (electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV) and an alternative informatics approach (Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score). The cohort included 21,335 encounters. Correlation coefficients indicated strong agreement between different methods of score calculation. Uncalibrated area under the receiver operating characteristics curves were 0.96 (95% CI, 0.95-0.97) for electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score and 0.87 (95% CI, 0.85-0.89) for electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV for inpatient mortality. The uncalibrated electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV standardized mortality ratio was 0.63 (0.59-0.66), demonstrating strong agreement with previous, prospective evaluation at the study center. The uncalibrated electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score standardized mortality ratio was 0.20 (0.18-0.21). All models required recalibrating (all Hosmer-Lemeshow goodness-of-fit, p < 0.001) and subsequently demonstrated acceptable goodness-of-fit when examined in a test subset (n = 5,334) of the cohort. CONCLUSIONS: Electronically derived intensive care acuity scores demonstrate very good to excellent discrimination and can be calibrated to institutional outcomes. This approach can facilitate both performance improvement and research initiatives and may offer a scalable strategy for comparison of interinstitutional PICU outcomes.

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OBJECTIVES: Characterize current practices for PICU-based rehabilitation, and physician perceptions and attitudes, barriers, resources, and outcome assessment in contemporary PICU settings. DESIGN: International, self-administered, quantitative, cross-sectional survey. SETTING: Online survey distributed from March 2017 to April 2017. PATIENTS OR SUBJECTS: Pediatric critical care physicians who subscribed to email distribution lists of the Pediatric Acute Lung Injury and Sepsis Investigators, the Pediatric Neurocritical Care Research Group, or the Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment study group, and visitors to the World Federation of Pediatric Intensive and Critical Care Societies website. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 170 subjects who began the survey, 148 completed it. Of those who completed the optional respondent information, most reported working in an academic medical setting and were located in the United States. The main findings were 1) a large majority of PICU physicians reported working in institutions with no guidelines for PICU-based rehabilitation, but expressed interest in developing and implementing such guidelines; 2) despite this lack of guidelines, an overwhelming majority of respondents reported that their current practices would involve consultation of multiple rehabilitation services for each case example provided; 3) PICU physicians believed that additional research evidence is needed to determine efficacy and optimal implementation of PICU-based rehabilitation; 4) PICU physicians reported significant barriers to implementation of PICU-based rehabilitation across centers; and 5) low routine assessment of long-term functional outcomes of PICU patients, although some centers have developed multidisciplinary follow-up programs. CONCLUSIONS: Physicians lack PICU-based rehabilitation guidelines despite great interest and current practices involving a high degree of PICU-based rehabilitation consultation. Data are needed to identify best practices and necessary resources in the delivery of ICU-based multidisciplinary rehabilitation and long-term functional outcomes assessment to optimize recovery of children and families affected by critical illness.

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