Post-discharge outcomes of hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C.

Introduction: Hospitalized children diagnosed with SARS-CoV-2-related conditions are at risk for new or persistent symptoms and functional impairments. Our objective was to analyze post-hospital symptoms, healthcare utilization, and outcomes of children previously hospitalized and diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C). Methods: Prospective, multicenter electronic survey of parents of children <18 years of age surviving hospitalization from 12 U.S. centers between January 2020 and July 2021. The primary outcome was a parent report of child recovery status at the time of the survey (recovered vs. not recovered). Secondary outcomes included new or persistent symptoms, readmissions, and health-related quality of life. Multivariable backward stepwise logistic regression was performed for the association of patient, disease, laboratory, and treatment variables with recovered status. Results: The children [n = 79; 30 (38.0%) female] with acute SARS-CoV-2 (75.7%) or MIS-C (24.3%) had a median age of 6.5 years (interquartile range 2.0-13.0) and 51 (64.6%) had a preexisting condition. Fifty children (63.3%) required critical care. One-third [23/79 (29.1%)] were not recovered at follow-up [43 (31, 54) months post-discharge]. Admission C-reactive protein levels were higher in children not recovered vs. recovered [5.7 (1.3, 25.1) vs. 1.3 (0.4, 6.3) mg/dl, p = 0.02]. At follow-up, 67% overall had new or persistent symptoms. The most common symptoms were fatigue (37%), weakness (25%), and headache (24%), all with frequencies higher in children not recovered. Forty percent had at least one return emergency visit and 24% had a hospital readmission. Recovered status was associated with better total HRQOL [87 (77, 95) vs. 77 (51, 83), p = 0.01]. In multivariable analysis, lower admission C-reactive protein [odds ratio 0.90 (95% confidence interval 0.82, 0.99)] and higher admission lymphocyte count [1.001 (1.0002, 1.002)] were associated with recovered status. Conclusions: Children considered recovered by their parents following hospitalization with SARS-CoV-2-related conditions had less symptom frequency and better HRQOL than those reported as not recovered. Increased inflammation and lower lymphocyte count on hospital admission may help to identify children needing longitudinal, multidisciplinary care. Clinical Trial Registration: ClinicalTrials.gov (NCT04379089).

Long-Term Neurobehavioral and Functional Outcomes of Pediatric Extracorporeal Membrane Oxygenation Survivors.

There are limited reports of neurobehavioral outcomes of children supported on extracorporeal membrane oxygenation (ECMO). This observational study aims to characterize the long-term (≥1 year) neurobehavioral outcomes, identify risk factors associated with neurobehavioral impairment, and evaluate the trajectory of functional status in pediatric ECMO survivors. Pediatric ECMO survivors ≥1-year postdecannulation and ≥3 years of age at follow-up were prospectively enrolled and completed assessments of adaptive behavior (Vineland Adaptive Behavior Scales, Third Edition [Vineland-3]) and functional status (Functional Status Scale [FSS]). Patient characteristics were retrospectively collected. Forty-one ECMO survivors cannulated at 0.0-19.8 years (median: 2.4 [IQR: 0.0, 13.1]) were enrolled at 1.3-12.8 years (median: 5.5 [IQR: 3.3, 6.5]) postdecannulation. ECMO survivors scored significantly lower than the normative population in the Vineland-3 Adaptive Behavior Composite (85 [IQR: 70, 99], P < 0.001) and all domains (Communication, Daily Living, Socialization, Motor). Independent risk factors for lower Vineland-3 composite scores included extracorporeal cardiopulmonary resuscitation, electrographic seizures during ECMO, congenital heart disease, and premorbid developmental delay. Of the 21 patients with impaired function at discharge (FSS ≥8), 86% reported an improved FSS at follow-up. Pediatric ECMO survivors have, on average, mild neurobehavioral impairment related to adaptive functioning years after decannulation. Continued functional recovery after hospital discharge is likely.

Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a child's neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood.

Follow-up after PICU discharge for patients with acquired brain injury: the role of an abbreviated neuropsychological evaluation and a return-to-school program.

Objective: To present the results of an abbreviated testing protocol used to screen for neurocognitive and psychological sequelae of critical illness among pediatric intensive care unit (PICU) survivors with acquired brain injury in our post-discharge follow-up programs, and describe our process for facilitating this population's return to academic life. Design: Retrospective cohort study. Setting: Neurocritical care follow-up programs at two U.S. academic, tertiary medical/surgical PICUs. Patients: Children age > 4 years enrolled in the neurocritical care follow-up programs (n=289) at these institutions who underwent neurocognitive and psychological testing between 2017-2021. Interventions: None. Measurements and Main Results: One month after discharge from the hospital, nearly half of the children and/or their parents (48%) in our neurocritical care follow-up programs identified some type of emotional or behavioral concern compared to their premorbid state, and 15% reported some type of cognitive concern. On evaluation, 35% of the children were given a new neurocognitive diagnosis. Neurocognitive domains regulated by the executive functioning system were the most commonly affected, including attention (54%), memory (31%) and processing speed (27%). One-quarter of the children were given a new psychological diagnosis, most commonly post-traumatic stress disorder (PTSD) or stress-related symptoms (12%). Over 80% of patients in the programs were given new recommendations for school, for both new academic services and new classroom accommodations. Over half of children (57%) were referred for comprehensive follow-up neuropsychological evaluation. Conclusions: Abbreviated neurocognitive and psychological evaluation successfully identifies the same deficits commonly found among PICU survivors who undergo longer, more complete testing protocols. When combined with services aimed at successfully re-integrating PICU survivors back to school, this focused evaluation can provide an effective and efficient means of screening for cognitive and emotional deficits among PICU survivors, and establish a rationale for early academic support upon the child's return to school.

Epidemiology of Intensive Care Admissions for Children in the US From 2001 to 2019.

Importance: Estimates of the number of US children receiving intensive care unit (ICU) care and ICU admission patterns over time are lacking. Objective: To determine how ICU admission patterns, use of critical care services, and the characteristics and outcomes of critically ill children have changed from 2001 to 2019. Design, Setting, and Participants: This population-based retrospective cohort study used data from the Healthcare Cost and Utilization Project's state inpatient databases from a total of 21 US states in 2001, 2004, 2010, 2016, and 2019. Hospitalized children aged 0 to 17 years, excluding newborns (during birth hospitalization), were included. Patients admitted to rehabilitation institutions or psychiatric hospitals were also excluded. Data were analyzed from July 2021 to December 2022. Exposures: Care in a nonneonatal ICU. Main Outcomes and Measures: From extracted patient data, International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision, Clinical Modification, codes were used to identify diagnoses, comorbid conditions, organ failures, and mechanical ventilation. Generalized linear Poisson regression and the Cuzick test were used to evaluate trends. US Census data were used to generate age- and sex-adjusted national estimates of ICU admissions and costs. Results: Of 2 157 991 pediatric admissions, 275 656 (12.8%) included ICU care. The mean (SD) age was 6.43 (6.10) years; 121 894 individuals were female (44.2%), and 153 731 were male (55.8%). From 2001 to 2019, the prevalence of ICU care among hospitalized children increased from 10.6% to 15.5%. The percentage of ICU admissions in children's hospitals rose from 51.2% to 85.1% (relative risk [RR], 1.66; 95% CI, 1.64-1.68). The percentage of children admitted to an ICU with an underlying comorbidity increased from 46.2% to 57.0% (RR, 1.23; 95% CI, 1.22-1.25), and the percentage with preadmission technology dependence increased from 16.4% to 23.5% (RR, 1.44; 95% CI, 1.40-1.48). The prevalence of multiple organ dysfunction syndrome increased from 6.8% to 21.0% (RR, 3.12; 95% CI, 2.98-3.26), while mortality decreased from 2.5% to 1.8% (RR, 0.72; 95% CI, 0.66-0.79). Hospital length of stay increased by 0.96 days (95% CI, 0.73-1.18) for ICU admissions from 2001 to 2019. After inflation adjustment, total costs for a pediatric admission involving ICU care nearly doubled between 2001 and 2019. Nationally, an estimated 239 000 children were admitted to a US ICU in 2019, corresponding to $11.6 billion in hospital costs. Conclusions and Relevance: In this study, the prevalence of children receiving ICU care in the US increased, as did length of stay, technology use, and associated costs. The US health care system must be equipped to care for these children in the future.

A Core Outcome Measurement Set for Pediatric Critical Care.

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.

Continuing Care For Critically Ill Children Beyond Hospital Discharge: Current State of Follow-up.

OBJECTIVES: Survivors of the PICU face long-term morbidities across health domains. In this study, we detail active PICU follow-up programs (PFUPs) and identify perceptions and barriers about development and maintenance of PFUPs. METHODS: A web link to an adaptive survey was distributed through organizational listservs. Descriptive statistics characterized the sample and details of existing PFUPs. Likert responses regarding benefits and barriers were summarized. RESULTS: One hundred eleven respondents represented 60 institutions located in the United States (n = 55), Canada (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Details for 17 active programs were provided. Five programs included broad PICU populations, while the majority were neurocritical care (53%) focused. Despite strong agreement on the need to assess and treat morbidity across multiple health domains, 29% were physician only programs, and considerable variation existed in services provided by programs across settings. More than 80% of all respondents agreed PFUPs provide direct benefits and are essential to advancing knowledge on long-term PICU outcomes. Respondents identified "lack of support" as the most important barrier, particularly funding for providers and staff, and lack of clinical space, though successful programs overcome this challenge using a variety of funding resources. CONCLUSIONS: Few systematic multidisciplinary PFUPs exist despite strong agreement about importance of this care and direct benefit to patients and families. We recommend stakeholders use our description of successful programs as a framework to develop multidisciplinary models to elevate continuity across inpatient and outpatient settings, improve patient care, and foster collaboration to advance knowledge.

Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.

Patterns of Organ Dysfunction in Critically Ill Children Based on PODIUM Criteria.

OBJECTIVES: The goal of this study was to determine the incidence, prognostic performance, and generalizability of the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) organ dysfunction criteria using electronic health record (EHR) data. Additionally, we sought to compare the performance of the PODIUM criteria with the organ dysfunction criteria proposed by the 2005 International Pediatric Sepsis Consensus Conference (IPSCC). METHODS: Retrospective observational cohort study of critically ill children at 2 medical centers in the United States between 2010 and 2018. We assessed prevalence of organ dysfunction based on the PODIUM and IPSCC criteria for each 24-hour period from admission to 28 days. We studied the prognostic performance of the criteria to discriminate in-hospital mortality. RESULTS: Overall, 22 427 PICU admissions met inclusion criteria, and in-hospital mortality was 2.3%. The cumulative incidence of each PODIUM organ dysfunction ranged from 15% to 30%, with an in-hospital mortality of 6% to 10% for most organ systems. The number of concurrent PODIUM organ dysfunctions demonstrated good-to-excellent discrimination for in-hospital mortality (area under the curve 0.87-0.93 for day 1 through 28) and compared favorably to the IPSCC criteria (area under the curve 0.84-0.92, P < .001 to P = .06). CONCLUSIONS: We present the first evaluation of the PODIUM organ dysfunction criteria in 2 EHR databases. The use of the PODIUM organ dysfunction criteria appears promising for epidemiologic and clinical research studies using EHR data. More studies are needed to evaluate the PODIUM criteria that are not routinely collected in structured format in EHR databases.

Family Outcomes After the Pediatric Intensive Care Unit: A Scoping Review.

BACKGROUND: Intensivists are increasingly attuned to the postdischarge outcomes experienced by families because patient recovery and family outcomes are interdependent after childhood critical illness. In this scoping review of international contemporary literature, we describe the evidence of family effects and functioning postpediatric intensive care unit (PICU) as well as outcome measures used to identify strengths and weaknesses in the literature. METHODS: We reviewed all articles published between 1970 and 2017 in PubMed, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), or the Cochrane Controlled Trials Registry. Our search used a combination of terms for the concept of "critical care/illness" combined with additional terms for the prespecified domains of social, cognitive, emotional, physical, health-related quality of life (HRQL), and family functioning. RESULTS: We identified 71 articles reporting on the postPICU experience of more than 2400 parents and 3600 families of PICU survivors in 8 countries. These articles used 101 different metrics to assess the various aspects of family outcomes; 34 articles also included open-ended interviews. Overall, most families experienced significant disruption in at least five out of six of our family outcomes subdomains, with themes of decline in mental health, physical health, family cohesion, and family finances identified. Almost all articles represented relatively small, single-center, or disease-specific observational studies. There was a disproportionate representation of families of higher socioeconomic status (SES) and Caucasian race, and there was much more data about mothers compared to fathers. There was also very limited information regarding outcomes for siblings and extended family members after a child's PICU stay. CONCLUSIONS: Significant opportunities remain for research exploring family functioning after PICU discharge. We recommend that future work include more diverse populations with respect to the critically ill child as well as family characteristics, include more intervention studies, and enrich existing knowledge about outcomes for siblings and extended family.

Postdischarge Outcome Domains in Pediatric Critical Care and the Instruments Used to Evaluate Them: A Scoping Review.

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.

Parental Mental Health Care After Their Child's Pediatric Intensive Care Hospitalization.

OBJECTIVES: Post-traumatic stress disorder, depression, and anxiety have all been found in parents of PICU survivors. How these research findings translate to actual use of mental health services by parents remains unknown. DESIGN: Retrospective observational cohort study. SETTING: Insurance claims data from 2006 to 2013 obtained from the IBM MarketScan Commercial Database. PATIENTS: Parents of PICU survivors. INTERVENTIONS: We examined rates of: 1) mental health diagnoses, 2) outpatient mental health visits, and 3) prescriptions for antidepressants and anxiolytics among parents, 6 months before and 6 months after their child's PICU admission, using each parent as their own control. MEASUREMENTS AND MAIN RESULTS: Of the 95,070 parents identified, 9.5% received a new mental health diagnosis in the 6 months after their child's PICU hospitalization, which represented a 110% increase from pre-PICU rates. A smaller proportion of parents were given new prescriptions for antidepressants (3.4%) and anxiolytics (3.9%) in the 6 months after their child's PICU hospitalization. Mothers were twice as likely to receive a new mental health diagnosis and be taking a new medication than fathers in the post-PICU period. The parental diagnosis of acute stress disorder or post-traumatic stress disorder increased by 87% from the pre-PICU to the post-PICU period. CONCLUSIONS: After their child's PICU hospitalization, the proportion of parents with a new mental health diagnosis nearly doubled. Mothers were at nearly twice the risk of receiving a new mental health diagnosis and receiving a new mental health medication compared with fathers. The proportion of parents receiving mental healthcare is much lower than the proportion reporting mental health symptoms in long-term outcomes studies. Whether this indicates a gap in healthcare delivery for parents with mental health symptoms remains unknown.

Post-Intensive-Care Syndrome for the Pediatric Neurologist.

The number of children who survive critical illness has steadily increased. However, lower mortality rates have resulted in a proportional increase in post-intensive-care morbidity. Critical illness in childhood affects a child's development, cognition, and family functioning. The constellation of physical, emotional, cognitive, and psychosocial symptoms that begin in the intensive care unit and continue after discharge has recently been termed post-intensive-care syndrome. A conceptual model of the post-intensive-care syndrome experienced by children who survive critical illness, their siblings, and parents has been coined post-intensive-care syndrome in pediatrics. Owing to their prolonged hospitalizations, the use of sedative medications, and the nature of their illness, children with primary neurological injury are among those at the highest risk for post-intensive-care syndrome in pediatrics. The pediatric neurologist participates in the care of children with acute brain injury throughout their hospitalization and remains involved after the patient leaves the hospital. Hence it is important for pediatric neurologists to become versed in the early recognition and management of post-intensive-care syndrome in pediatrics. In this review, we discuss the current knowledge regarding post-intensive-care syndrome in pediatrics and its risk factors. We also discuss our experience establishing Pediatric Neurocritical Care Recovery Programs at two large academic centers. Last, we provide a battery of validated tests to identify and manage the different aspects of post-intensive-care syndrome in pediatrics, which have been successfully implemented at our institutions. Dissemination of this "road map" may assist others interested in establishing recovery programs, therefore mitigating the burden of post-intensive-care morbidity in children.

RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness.

BACKGROUND: Decreased TNF-α production in whole blood after ex vivo LPS stimulation indicates suppression of the Toll-like receptor (TLR)4 pathway. This is associated with increased mortality in pediatric influenza critical illness. Whether antiviral immune signaling pathways are also suppressed in these patients is unclear. OBJECTIVES: We sought to evaluate suppression of the TLR4 and the antiviral retinoic acid-inducible gene-I (RIG-I) pathways with clinical outcomes in children with severe influenza infection. METHODS: In this 24-center, prospective, observational cohort study of children with confirmed influenza infection, blood was collected within 72 hours of intensive care unit admission. Ex vivo whole blood stimulations were performed with matched controls using the viral ligand polyinosinic-polycytidylic acid-low-molecular-weight/LyoVec and LPS to evaluate IFN-α and TNF-α production capacities (RIG-I and TLR4 pathways, respectively). RESULTS: Suppression of either IFN-α or TNF-α production capacity was associated with longer duration of mechanical ventilation and hospitalization, and increased organ dysfunction. Children with suppression of both RIG-I and TLR4 pathways (n = 33 of 103 [32%]) were more likely to have prolonged (≥7 days) multiple-organ dysfunction syndrome (30.3% vs 8.6%; P = .004) or prolonged hypoxemic respiratory failure (39.4% vs 11.4%; P = .001) compared with those with single- or no pathway suppression. CONCLUSIONS: Suppression of both RIG-I and TLR4 signaling pathways, essential for respective antiviral and antibacterial responses, is common in previously immunocompetent children with influenza-related critical illness and is associated with bacterial coinfection and adverse outcomes. Prospective testing of both pathways may aid in risk-stratification and in immune monitoring.

Sleep Measure Validation in a Pediatric Neurocritical Care Acquired Brain Injury Population.

BACKGROUND/OBJECTIVE: Lingering morbidities including physical, cognitive, emotional, and psychosocial sequelae, termed the Post-Intensive Care Syndrome, persist years after pediatric neurocritical care (PNCC) hospitalization. Sleep disturbances impact other Post-Intensive Care Syndrome domains and are under-evaluated to date due to a lack of appropriate measurement tools. The present study evaluated the validity of the Sleep Disturbance Scale for Children (SDSC) to address the growing need for assessing sleep problems after PNCC. METHODS: We conducted a prospective observational study of youth aged 3-17 years with acquired brain injury (N = 69) receiving care through longitudinal PNCC programs at two tertiary academic medical centers. Parents completed the SDSC and provided proxy reports of internalizing symptoms, health-related quality of life (HRQOL), fatigue, pain behavior, and cognitive function within 3 months of hospital discharge. Evidence for the validity of the SDSC was established by utilizing the full sample for psychosocial measure comparisons and by comparing SDSC outcomes by severity (Low Risk, Mild-Moderate Risk, and High Risk defined by reported standardized T-scores). RESULTS: Internal consistency of the SDSC was good (α = .81). Within the full sample, increased sleep disturbances on the SDSC were significantly correlated with Post-Intensive Care Syndrome measures, including worse physical (r = .65), psychological (r = .62), and cognitive (r = - .74) sequelae. Youth in the High Risk group evidenced greater dysfunction in mental acuity, pain behavior, internalizing symptoms, and social engagement. Findings revealed both statistically and clinically significant impacts of sleep disturbances as measured by the SDSC on HRQOL. CONCLUSIONS: The SDSC is a valid and reliable measure for assessing sleep disturbances in children after PNCC. Results support the use of the SDSC to measure sleep disturbances after PNCC. Targeted interventions for sleep disturbances may be key to overall patient recovery.

Sleep-Wake Disturbances After Acquired Brain Injury in Children Surviving Critical Care.

BACKGROUND: Sleep-wake disturbances are underevaluated among children with acquired brain injury surviving critical care. We aimed to quantify severity, phenotypes, and risk factors for sleep-wake disturbances. METHODS: We performed a prospective cohort study of 78 children aged ≥3 years with acquired brain injury within three months of critical care hospitalization. Diagnoses included traumatic brain injury (n = 40), stroke (n = 11), infectious or inflammatory disease (n = 10), hypoxic-ischemic injury (n = 9), and other (n = 8). Sleep Disturbances Scale for Children standardized T scores measured sleep-wake disturbances. Overall sleep-wake disturbances were dichotomized as any total or subscale T score ≥60. Any T score ≥70 defined severe sleep-wake disturbances. Subscale T scores ≥60 identified sleep-wake disturbance phenotypes. RESULTS: Sleep-wake disturbances were identified in 44 (56%) children and were classified as severe in 36 (46%). Sleep-wake disturbances affected ≥33% of patients within each diagnosis and were not associated with severity of illness measures. The most common phenotype was disturbance in initiation and maintenance of sleep (47%), although 68% had multiple concurrent sleep-wake disturbance phenotypes. One third of all patients had preadmission chronic conditions, and this increased risk for sleep-wake disturbances overall (43% vs 21%, P = 0.04) and in the traumatic brain injury subgroup (52% vs 5%, P = 0.001). CONCLUSIONS: Over half of children surviving critical care with acquired brain injury have sleep-wake disturbances. Most of these children have severe sleep-wake disturbances independent of severity of illness measures. Many sleep-wake disturbances phenotypes were identified, but most children had disturbance in initiation and maintenance of sleep. Our study underscores the importance of evaluating sleep-wake disturbances after acquired brain injury.

Postintensive Care Syndrome in Pediatric Critical Care Survivors: Therapeutic Options to Improve Outcomes After Acquired Brain Injury.

PURPOSE OF REVIEW: Children surviving the pediatric intensive care unit (PICU) with neurologic illness or injury have long-term morbidities in physical, cognitive, emotional, and social functioning termed postintensive care syndrome (PICS). In this article, we review acute and longitudinal management strategies available to combat PICS in children with acquired brain injury. RECENT FINDINGS: Few intervention studies in this vulnerable population target PICS morbidities. Small studies show promise for both inpatient- and outpatient-initiated therapies, mainly focusing on a single domain of PICS and evaluating heterogeneous populations. While evaluating the effects of interventions on longitudinal PICS outcomes is in its infancy, longitudinal clinical programs targeting PICS are increasing. A multidisciplinary team with inpatient and outpatient presence is necessary to deliver the holistic integrated care required to address all domains of PICS in patients and families. While PICS is increasingly recognized as a chronic problem in PICU survivors with acquired brain injury, few interventions have targeted PICS morbidities. Research is needed to improve physical, cognitive, emotional, and social outcomes in survivors and their families.

Post-Intensive Care Syndrome: Educational Interventions for Parents of Hospitalized Children.

BACKGROUND: Targeted education to help parents and caregivers recognize the signs and symptoms of post-intensive care syndrome may increase their awareness and willingness to seek support during their child's admission. The optimal strategy for this education has not been established. METHODS: A pilot study to test 3 educational strategies for caregivers of pediatric intensive care unit patients. The 3 strategies were compared using the Practical, Robust Implementation and Sustainability Model framework for effectiveness of the education, the effect of each educational intervention on the intensive care unit nursing environment, and costs. Nursing responses were scored on a 3-point Likert scale. RESULTS: A total of 62 caregivers randomly received 1 of 3 educational strategies: brochures (n = 22), scripted conversation (n = 20), or a 3-minute video (n = 20). All 3 strategies were associated with a notable improvement in understanding of post-intensive care syndrome, with no single strategy being superior. Nineteen bedside nurses completed a survey on how daily workflow was affected and education was perceived. The survey indicated that all 3 interventions minimally disrupted workflow and all were recognized as useful. Final analysis indicated that brochures have the greatest likelihood of successful and sustainable implementation in the study hospital. CONCLUSION: Simple, low-cost education can improve caregivers' knowledge of post-intensive care syndrome and can be well supported by nursing staff. To ensure sustainable implementation, the characteristics of the unit should be considered when selecting an educational program.