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Surgeons are uniquely poised to conduct research to improve patient care, yet a gap often exists between the clinician's desire to guide patient care with causal evidence and having adequate training necessary to produce causal evidence. This guide aims to address this gap by providing clinically relevant examples to illustrate necessary assumptions required for clinical research to produce causal estimates.

Objectives To evaluate whether delirium during pediatric critical illness is associated with post-discharge health-related quality of life. Design Retrospective cohort study. Setting Academic tertiary care center. Patients Children 1 month to 18 years old admitted to the PICU or cardiac ICU and enrolled in the Seattle Children's Hospital Outcomes Assessment Program. Interventions None. Measurements and main results Delirium was assessed twice daily using the Cornell Assessment of Pediatric Delirium; a score greater than or equal to 9 (with fluctuating level of arousal for children with developmental disability) indicated delirium. Baseline (pre-admission) and post-discharge health-related quality of life were assessed by the Pediatric Quality of Life Inventory (Mapi Research Trust, Lyon, France) or the Functional Status II-R (for children with developmental disability). Among 534 patients, delirium was common (44%), as was clinically important decline in health-related quality of life (≥ 4.5 points) from baseline to follow-up (22%), measured at median 6.6 weeks post-hospital discharge (interquartile range, 5.1-8.5). On univariate analysis, children with delirium had similar likelihood of health-related quality of life decline compared with those without (25.5% vs 19.7%; p = 0.1). Using multivariable logistic regression adjusting for age, medical complexity, predicted risk of mortality, admission diagnosis, receipt of noninvasive ventilation, hospital length of stay, time to follow-up, and parent age, delirium was independently associated with health-related quality of life decline among children assessed by the Pediatric Quality of Life Inventory (adjusted odds ratio, 2.0; 95% CI, 1.1-3.5). Among children evaluated with the Functional Status II-R, delirium was not independently associated with health-related quality of life decline (odds ratio, 1.4; 95% CI, 0.6-3.2). In both groups, longer time to follow-up was also independently associated with improvements in health-related quality of life. Conclusions Delirium during the ICU stay is associated with decline in health-related quality of life from baseline to post-discharge follow-up among children assessed by the Pediatric Quality of Life Inventory, who were generally characterized by normal baseline cognitive function and less medical comorbidity. This association was not present among children assessed by the Functional Status II-R, potentially due to their higher overall risk of health-related quality of life decline, or other clinical differences that modify the effects of delirium in this group.

Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to single-center pediatric cohorts. We used pediatric criteria to determine the prevalence, risk factors, and outcomes of MODS among critically injured children in a national pediatric intensive care unit (PICU) database.We conducted a retrospective cohort study of PICU patients 1 month to 17 years with traumatic injury in the Virtual Pediatric Systems, LLC database from 2009 to 2017. We used International Pediatric Sepsis Consensus Conference criteria to identify MODS on Day 1 of PICU admission and estimated the risk of mortality and poor functional outcome (Pediatric Overall/Cerebral Performance Category ≥3 with ≥1 point worsening from baseline) for MODS and for each type of organ dysfunction using generalized linear Poisson regression adjusted for age, comorbidities, injury type and mechanism, and postoperative status.Multiple organ dysfunction syndrome was present on PICU Day 1 in 23.1% of 37,177 trauma patients (n = 8,592), with highest risk among patients with injuries associated with drowning, asphyxiation, and abuse. Pediatric intensive care unit mortality was 20.1% among patients with MODS versus 0.5% among patients without MODS (adjusted relative risk, 32.3; 95% confidence interval, 24.1-43.4). Mortality ranged from 1.5% for one dysfunctional organ system to 69.1% for four or more organ systems and was highest among patients with hematologic dysfunction (43.3%) or renal dysfunction (29.6%). Death or poor functional outcome occurred in 46.7% of MODS patients versus 8.3% of patients without MODS (adjusted relative risk, 4.3; 95% confidence interval 3.4-5.3).Multiple organ dysfunction syndrome occurs more frequently following pediatric trauma than previously reported and is associated with high risk of morbidity and mortality. Based on existing literature using identical methodology, both the prevalence and mortality associated with MODS are higher among trauma patients than the general PICU population. Consideration of early organ dysfunction in addition to injury severity may aid prognostication following pediatric trauma.Prognostic and Epidemiological; Level III.

OBJECTIVES To evaluate which individual elements of health-related quality of life contribute most to decline in overall health-related quality of life status following pediatric critical care. DESIGN Retrospective cohort study. SETTING Seattle Children's Hospital. PATIENTS ICU patients age 1 month to 18 years admitted between December 2011 and February 2017. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We assessed health-related quality of life decline from baseline to postdischarge (median, 6 wk) and determined the individual items of the Pediatric Quality of Life Inventory Infant Scales (< 2 yr) and Generic Core Scales (2-18 yr) with the highest prevalence of decline. We used multivariable regression to estimate the risk of decline in each of seven thematic categories by patient age, baseline health status, diagnosis, Pediatric Risk of Mortality score, and ICU length of stay. Decline from baseline health-related quality of life occurred in 22.5% of 539 patients. Items most commonly affected for infants less than 2 years were primarily emotional (cranky/crying, sleep, and self-soothing). Children 2-18 years most commonly experienced declines in physical functioning (play/exercise, lifting, and pain). Across the entire cohort, declines in categories of energy (31.5%), activity (31.0%), sleep (28.0%), and fear (24.7%) were most commonly endorsed. Risk of decline in each category varied with patient age, medical complexity, and diagnosis. CONCLUSIONS Deconditioning, sleep, fear, and pain are important targets for intervention to improve health-related quality of life outcomes for critically ill children.

ImportanceEstimates of the number of US children receiving intensive care unit (ICU) care and ICU admission patterns over time are lacking.ObjectiveTo 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 ParticipantsThis 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.ExposuresCare in a nonneonatal ICU.Main Outcomes and MeasuresFrom 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.ResultsOf 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 RelevanceIn 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.

Objectives To evaluate the optimal timing of tracheostomy for injured adolescents. Design Retrospective cohort study. Setting Trauma facilities in the United States. Patients Adolescents (age 12-17 yr) in the National Trauma Data Bank (2007-2016) who were ventilated for greater than 24 hours and survived to discharge. Interventions None. Measurements and main results After stratifying by traumatic brain injury diagnosis, we compared ICU and hospital length of stay, pneumonia, and discharge disposition of patients with tracheostomy prior to three cut points (3, 7, and 14 d after admission) to 1) patients intubated at least as long as each cut point and 2) patients with tracheostomy on or after each cut point. Of 11,045 patients, 1,391 (12.6%) underwent tracheostomy. Median time to tracheostomy was 9 days (interquartile range, 6-13 d) for traumatic brain injury and 7 days (interquartile range, 3-12 d) for nontraumatic brain injury patients. Nontraumatic brain injury patients with tracheostomy prior to 7 days had 5.6 fewer ICU days (-7.8 to -3.5 d) and 5.7 fewer hospital days (-8.8 to -2.7 d) than patients intubated greater than or equal to 7 days and had 14.8 fewer ICU days (-19.6 to -10.0 d) and 15.3 fewer hospital days (-21.7 to -8.9 d) than patients with tracheostomy greater than or equal to 7 days. Similar differences were observed at 14 days but not at 3 days for both traumatic brain injury and nontraumatic brain injury patients. At the 3- and 7-day cut points, both traumatic brain injury and nontraumatic brain injury patients with tracheostomy prior to the cut point had lower risk of pneumonia and risk of discharge to a facility than those with tracheostomy after the cut point. Conclusions For injured adolescents, tracheostomy less than 7 days after admission was associated with improved in-hospital outcomes compared with those who remained intubated greater than or equal to 7 days and with those with tracheostomy greater than or equal to 7 days. Tracheostomy between 3 and 7 days may be the optimal time point when prolonged need for mechanical ventilation is anticipated; however, unmeasured consequences of tracheostomy such as long-term complications and care needs must also be considered.

Pain may be a modifiable risk factor for lower health-related quality of life after pediatric critical illness.To evaluate the association between severe pain experienced in the (pediatrc intensive care unit) and postdischarge health-related quality of life.This was a retrospective cohort study. Children aged 1 month to 18 years admitted to the pediatric intensive care unit and enrolled in the Seattle Children's Hospital Outcomes Assessment Program were included. Pain was assessed every 2 h by bedside nursing staff using a behavioral pain scale or numeric pain scale. A day of severe pain was defined as a pediatric intensive care unit day with ≥25% of pain scores ≥7/10. Baseline (preadmission) and postdischarge (median 6 weeks) health-related quality of life was assessed by the Pediatric Quality of Life Inventory (PedsQL™) or the Stein Jessop Functional Status II-R (FS II-R, for children with developmental disability). The cohort was stratified by diagnosis category (surgical vs. medical), and associations were measured using linear regression models.Among 546 patients, 11.9% experienced ≥1 day of severe pain. In multivariable linear regression, each day of severe pain was independently associated with a lower postdischarge health-related quality of life score by 3.6 points (95% CI -6.3 to -0.9) adjusted for baseline health-related quality of life score, age, baseline cognitive function, days with multi-organ dysfunction, pediatric intensive care unit length of stay, and decline in overall function. This association was stronger among surgical patients than medical patients with each day of severe pain resulting in a lower postdischarge health-related quality of life score by 5.3 points (95% CI -9.6 to -0.9) versus 2.6 points (95% CI -5.8 to 0.6). Surgical patients had lower postdischarge emotional functioning than physical functioning subdomain scores.Children who experience severe pain in the pediatric intensive care unit have lower postdischarge health-related quality of life adjusting for baseline health-related quality of life, particularly among children who have undergone surgery. Attention to pain management may be important to improve postdischarge health-related quality of life.

BACKGROUND/OBJECTIVE: Optimizing blood pressure is an important target for intervention following pediatric traumatic brain injury (TBI). Existing literature has examined the association between systolic blood pressure (SBP) and outcomes. Mean arterial pressure (MAP) is a better measure of organ perfusion than SBP and is used to determine cerebral perfusion pressure but has not been previously examined in relation to outcomes after pediatric TBI. We aimed to evaluate the strength of association between MAP-based hypotension early after hospital admission and discharge outcome, and to contrast the relative strength of association of hypotension with outcome between MAP-based and SBP-based blood pressure percentiles. METHODS: We examined the association between lowest age-specific MAP percentile within 12 hours after pediatric intensive care unit admission and poor discharge outcome (in-hospital death or transfer to a skilled nursing facility) in children with severe (Glasgow Coma Scale score

Background: Informal caregivers for persons with traumatic brain injury (TBI) face a range of unique issues, and racial/ethnic group differences in caregiver challenges are poorly understood. We undertook a scoping study of peer-reviewed literature to assess the quantity and quality of available research describing differences by race/ethnicity in informal caregiving roles and burden. Methods: Using Arksey and O'Malley's framework and guided by the Preferred Reporting Items of Systematic Reviews and Meta-analyses Extension for Scoping Reviews, we conducted electronic searches of PubMed, CINAHL, PsycARTICLES, PsycINFO, Social Work Abstracts, Embase, and Scopus to identify peer-reviewed studies that examined TBI informal caregiver burden and reported on the influences of race or ethnicity. Results: Among 4523 unique publications identified and screened, 11 studies included sufficient race/ethnicity data and were included in the analysis. Of these, six studies described civilian populations and five described military Veterans Affairs (VA). Included studies revealed that nonwhite caregivers and white caregivers use different approaches and coping strategies in their caregiving role. Some studies found differences in caregiver burden by race or ethnicity, others did not. Most were limited by a small sample size and overdependence on assessment tools not validated for the purposes or populations for which they were used. This was particularly true for race/ethnicity as a factor in TBI caregiver burden in VA groups, where essential characteristics moderate the association of race/ethnicity with socioeconomic factors. Conclusions: This scoping study highlights the paucity of information on race/ethnicity as a factor in TBI caregiver burden and roles, and suggests that innovative and alternative approaches to research are needed to explore needed changes in practice.

Objectives Pediatric protocols to guide allocation of limited resources during a disaster lack data to validate their use. The 2011 Pediatric Emergency Mass Critical Care Task Force recommended that expected duration of critical care be incorporated into resource allocation algorithms. We aimed to determine whether currently available pediatric illness severity scores can predict duration of critical care resource use. Design Retrospective cohort study. Setting Seattle Children's Hospital. Patients PICU patients admitted 2016-2018 for greater than or equal to 12 hours (n = 3,206). Interventions None. Measurements and main results We developed logistic and linear regression models in two-thirds of the cohort to predict need for and duration of PICU resources based on Pediatric Risk of Mortality-III, Pediatric Index of Mortality-3, and serial Pediatric Logistic Organ Dysfunction-2 scores. We tested the predictive accuracy of the models with the highest area under the receiver operating characteristic curve (need for each resource) and R (duration of use) in a validation cohort of the remaining one of three of the sample and among patients admitted during one-third of the sample and among patients admitted during surges of respiratory illness. Pediatric Logistic Organ Dysfunction score calculated 12 hours postadmission had higher predictive accuracy than either Pediatric Risk of Mortality or Pediatric Index of Mortality scores. Models incorporating 12-hour Pediatric Logistic Organ Dysfunction score, age, Pediatric Overall Performance Category, Pediatric Cerebral Performance Category, chronic mechanical ventilation, and postoperative status had an area under the receiver operating characteristic curve = 0.8831 for need for any PICU resource (positive predictive value 80.2%, negative predictive value 85.9%) and area under the receiver operating characteristic curve = 0.9157 for mechanical ventilation (positive predictive value 85.7%, negative predictive value 89.2%) within 7 days of admission. Models accurately predicted greater than or equal to 24 hours of any resource use for 78.9% of patients and greater than or equal to 24 hours of ventilation for 83.1%. Model fit and accuracy improved for prediction of resource use within 3 days of admission, and was lower for noninvasive positive pressure ventilation, vasoactive infusions, continuous renal replacement therapy, extracorporeal membrane oxygenation, and length of stay. Conclusions A model incorporating 12-hour Pediatric Logistic Organ Dysfunction score performed well in estimating how long patients may require PICU resources, especially mechanical ventilation. A pediatric disaster triage algorithm that includes both likelihood for survival and for requiring critical care resources could minimize subjectivity in resource allocation decision-making.

The objective of this article was to identify demographic and clinical factors associated with early recurrent arrest (RA) (

BACKGROUND: Results of recent studies suggest that the incidence and mortality of ARDS may be higher than previously thought in pediatric trauma patients. We conducted a systematic review of the literature on incidence, risk factors, prognostic factors, and outcomes of ARDS after pediatric trauma in the ICU. METHODS: Medical literature databases were searched up to April 2020. Guidelines for reporting systematic reviews and meta-analyses were followed. Articles that reported quantitative data with regard to the incidence, risk factors, prognostic factors, mortality, or other outcomes for ARDS in subjects with pediatric trauma admitted to the ICU were included. Two authors independently screened and assessed eligibility of all identified studies, collected data, and assessed the methodological quality of selected studies. Data extraction was performed by using a standardized data extraction sheet. Quality assessment was performed by using the Newcastle-Ottawa scale for cohort studies. A meta-analysis was not performed because the studies used overlapping cohorts or different ARDS criteria. RESULTS: Nine studies were included. The incidence was reported in 4 studies, risk factors in 1, mortality in 7, and other outcomes in 2. The largest cohort included 148,749 subjects from a national trauma database. The ARDS incidence was 1.8%–7.6% when using adult ARDS criteria, with 1.8% in the largest cohort, and 4.2% when using pediatric ARDS criteria. Mortality was 7.6%–22.9% when using adult ARDS criteria and 11.1%–34.0% when using the pediatric ARDS criteria. Identified risk factors included mechanism of injury, higher injury severity scores, abnormal breathing frequencies, and lower Glasgow coma scale scores at hospital presentation. ARDS was associated with a longer duration of mechanical ventilation, longer ICU and hospital length of stay, and a higher likelihood of requiring post-discharge care. CONCLUSIONS: The ARDS incidence of 4.2% in the subjects with pediatric trauma in the ICU was comparable with 3.2% in the general pediatric ICU population; however, mortality associated with trauma-associated ARDS was higher and more commonly due to multi-system organ failure rather than hypoxemia.

PURPOSE: Health-related quality of life (HRQL) has been identified as one of the core outcomes most important to assess following pediatric critical care, yet there are no data on the use of HRQL in pediatric critical care research. We aimed to determine the HRQL instruments most commonly used to assess children surviving critical care and describe study methodology, patient populations, and instrument characteristics to identify areas of deficiency and guide investigators conducting HRQL research. METHODS: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Registry for studies evaluating pediatric critical care survivors published 1970-2017. We used dual review for article selection and data extraction. RESULTS: Of 60,349 citations, 66 articles met inclusion criteria. The majority of studies were observational (89.4%) and assessed HRQL at one post-discharge time-point (86.4%), and only 10.6% of studies included a baseline assessment. Time to the first follow-up assessment ranged from 1 month to 10 years post-hospitalization (median 3 years, IQR 0.5-6). For 26 prospective studies, the median follow-up time was 0.5 years [IQR 0.25-1]. Parent/guardian proxy-reporting was used in 83.3% of studies. Fifteen HRQL instruments were employed, with four used in >5% of articles: the Health Utility Index (n=22 articles), the Pediatric Quality of Life Inventory (n=17), the Child Health Questionnaire (n=16), and the 36-Item Short Form Survey (n=9). CONCLUSION: HRQL assessment in pediatric critical care research has been centered around four instruments, though existing literature is limited by minimal longitudinal follow-up and infrequent assessment of baseline HRQL.

Rationale: Poor outcomes of adults surviving critical illness are well documented, but data in children are limited.Objectives: To identify factors associated with worse postdischarge function and ...

Mortality from pediatric sepsis has steadily declined over the past several decades; however, little is known about morbidity among survivors. We aimed to determine the prevalence of and risk factors for failure to recover to baseline health-related quality of life following community-acquired pediatric sepsis.Retrospective cohort study.Seattle Children's Hospital.Children aged 1 month to 21 years admitted to the inpatient wards or ICUs from 2012 to 2015 who met 2005 consensus sepsis criteria within 4 hours of hospitalization and were enrolled in the hospital's Outcomes Assessment Program with baseline, admission, and post-discharge health-related quality of life data available.None.We assessed health-related quality of life with the Pediatric Quality of Life Inventory for pre-admission baseline, admission, and post-discharge (median, 31 d) status. We determined associations between patient and illness characteristics with failure to recover within 4.5 points of baseline at follow-up (the minimum clinically significant difference between two scores). Of 790 patients, 23.8% failed to recover to baseline health-related quality of life at follow-up. Factors associated with failure to recover were septic shock, older age, private insurance, complex chronic disease, immune compromise, CNS infection or bacteremia, ICU admission, and longer length of stay. On multivariable analysis controlling for time to follow-up, failure to recover was independently associated with septic shock (relative risk, 1.79; 95% CI, 1.24-2.58), older age (relative risk, 1.02/yr; 95% CI, 1.01-1.05), immune compromise (relative risk, 1.83; 95% CI, 1.40-2.40), and length of stay (relative risk, 1.03/d; 95% CI, 1.01-1.04).Nearly one-quarter of children surviving hospitalization for community-acquired sepsis experienced a clinically significant deterioration in health-related quality of life. We identify risk factors for poor outcomes following sepsis and highlight the need for ongoing evaluation and treatment by primary and specialty care providers for pediatric sepsis survivors after hospital discharge.

Improved understanding of the relationship between patient age and acute respiratory distress syndrome (ARDS) development and mortality following traumatic injury may help facilitate generation of new hypotheses about ARDS pathophysiology and the role of novel treatments to improve outcomes across the age spectrum.We conducted a retrospective cohort study of trauma patients included in the National Trauma Data Bank who were admitted to an intensive care unit from 2007 to 2016. We determined ARDS incidence and mortality across eight age groups for the entire 10-year study period and by year. We used generalized linear Poisson regression models adjusted for underlying mortality risk (injury mechanism, Injury Severity Score, admission Glasgow Coma Scale score, admission heart rate, and admission hypotension).Acute respiratory distress syndrome occurred in 3.1% of 1,297,190 trauma encounters. Acute respiratory distress syndrome incidence was lowest among pediatric patients and highest among adults aged 35 to 64 years. Acute respiratory distress syndrome mortality was highest among patients 80 years or older (43.9%), followed by 65 to 79 years (30.6%) and 4 years or younger (25.3%). The relative risk of mortality associated with ARDS was highest among the pediatric age groups, with an adjusted relative risk (aRR) of 2.06 (95% confidence interval [CI], 1.72-2.70) among patients 4 years or younger compared with an aRR of 1.51 (95% CI, 1.42-1.62) for the entire cohort. Acute respiratory distress syndrome mortality increased over the 10-year study period (aRR, 1.03 per year; 95% CI, 1.02-1.05 per year), whereas all-cause mortality decreased (aRR, 0.98 per year; 95% CI, 0.98-0.99 per year).While ARDS development following traumatic injury was most common in middle-aged adults, patients 4 years or younger and 65 years or older with ARDS experienced the highest burden of mortality. Children 4 years or younger were disproportionately affected by ARDS relative to their low underlying mortality following trauma that was not complicated by ARDS. Acute respiratory distress syndrome-associated mortality following trauma has worsened over the past decade, emphasizing the need for new prevention and treatment strategies.Prognostic/epidemiological study, level III.

Background Unplanned hospital readmissions are associated with morbidity and high cost. Existing literature on readmission after trauma has focused on how injury characteristics are associated with readmission. We aimed to evaluate how psychosocial determinants of health and complications of hospitalization combined with injury characteristics affect risk of readmission after trauma. Materials and methods We conducted a retrospective cohort study of adult trauma admissions from July 2015 to September 2017 to Harborview Medical Center in Seattle, Washington. We assessed patient, injury, and hospitalization characteristics and estimated associations between risk factors and unplanned 30-d readmission using multivariable generalized linear Poisson regression models. Results Of 8916 discharged trauma patients, 330 (3.7%) had an unplanned 30-d readmission. Patients were most commonly readmitted with infection (41.5%). Independent risk factors for readmission among postoperative patients included public insurance (adjusted Relative Risk (aRR) 1.34, 95% CI 1.02-1.76), mental illness (aRR 1.39, 1.04-1.85), and chronic renal failure (aRR 2.17, 1.39-3.39); undergoing abdominal, thoracic, or neurosurgical procedures; experiencing an index hospitalization surgical site infection (aRR 4.74, 3.00-7.50), pulmonary embolism (aRR 3.38, 2.04-5.60), or unplanned ICU readmission (aRR 1.74, 1.16-2.62); shorter hospital stay (aRR 0.98/d, 0.97-0.99), and discharge to jail (aRR 4.68, 2.63-8.35) or a shelter (aRR 4.32, 2.58-7.21). Risk factors varied by reason for readmission. Injury severity, trauma mechanism, and body region were not independently associated with readmission risk. Conclusions Psychosocial factors and hospital complications were more strongly associated with readmission after trauma than injury characteristics. Improved social support and follow-up after discharge for high-risk patients may facilitate earlier identification of postdischarge complications.

IMPORTANCE: The pediatric intensive care unit (PICU) exposes children to stressful experiences with potential long-term psychological repercussions. However, current understanding of post-PICU psychological outcomes is incomplete. OBJECTIVE: To systematically review and evaluate reported long-term psychological outcomes among children previously admitted to the PICU. DATA SOURCES: A systematic search of the Cumulative Index to Nursing and Allied Health Literature, Embase, MEDLINE (PubMed), and PsycINFO was conducted from database inception to June 2021. Search terms included phrases related to intensive care (eg, intensive care units and critical care) and terms for psychological disorders (eg, posttraumatic stress disorder, depressive disorder, conduct disorder, and neurodevelopmental disorder) limited to the pediatric population. STUDY SELECTION: This systematic review and meta-analysis included randomized clinical trials and observational studies reporting psychological disorders among children younger than 18 years who were admitted to the PICU with follow-up for at least 3 months. Psychological disorders were defined using the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Children were excluded if they were admitted to the PICU for primary brain conditions (eg, traumatic brain injury, meningoencephalitis, and brain tumors) or discharged to the home for palliative care. DATA EXTRACTION AND SYNTHESIS: Titles and abstracts were independently screened by 2 reviewers, with data extraction conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Data were pooled using a random-effects model during meta-analysis. MAIN OUTCOMES AND MEASURES: Age-corrected IQ scores and long-term psychological outcomes measured by scales such as the Child Behavior Checklist (higher scores indicate more behavioral problems) among children admitted to the PICU. RESULTS: Of 9193 records identified, 31 independent studies (5 randomized clinical trials and 26 observational studies) involving 7786 children (mean age, 7.3 years [95% CI, 6.2-8.4 years]; 4267 boys [54.8%]; race and ethnicity were not reported by all studies) admitted to the PICU were included. Overall, 1 of 19 children (5.3%) to 14 of 16 children (88.0%) previously admitted to the PICU were reported to have at least 1 psychological disorder. Studies that examined posttraumatic stress disorder reported that 6 of 60 children (10.0%) to 31 of 102 children (30.4%) met the diagnostic criteria for the disorder at 3 to 6 months of follow-up. Compared with healthy children, those admitted to the PICU had lower IQ scores at 1 to 2 years of follow-up (mean, 89.40 points [95% CI, 88.33-90.47 points] vs 100.70 points [95% CI, 99.43-101.97 points]; P

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.

OBJECTIVES To assess the incidence, severity, and outcomes of pediatric acute respiratory distress syndrome following trauma using Pediatric Acute Lung Injury Consensus Conference criteria. DESIGN Retrospective cohort study. SETTING Level 1 pediatric trauma center. PATIENTS Trauma patients less than or equal to 17 years admitted to the ICU from 2009 to 2017. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We queried electronic health records to identify patients meeting pediatric acute respiratory distress syndrome oxygenation criteria for greater than or equal to 6 hours and determined whether patients met complete pediatric acute respiratory distress syndrome criteria via chart review. We estimated associations between pediatric acute respiratory distress syndrome and outcome using generalized linear Poisson regression adjusted for age, injury mechanism, Injury Severity Score, and serious brain and chest injuries. Of 2,470 critically injured children, 103 (4.2%) met pediatric acute respiratory distress syndrome criteria. Mortality was 34.0% among pediatric acute respiratory distress syndrome patients versus 1.7% among patients without pediatric acute respiratory distress syndrome (adjusted relative risk, 3.7; 95% CI, 2.0-6.9). Mortality was 50.0% for severe pediatric acute respiratory distress syndrome at onset, 33.3% for moderate, and 30.5% for mild. Cause of death was neurologic in 60.0% and multiple organ failure in 34.3% of pediatric acute respiratory distress syndrome nonsurvivors versus neurologic in 85.4% of nonsurvivors without pediatric acute respiratory distress syndrome (p = 0.001). Among survivors, 77.1% of pediatric acute respiratory distress syndrome patients had functional disability at discharge versus 30.7% of patients without pediatric acute respiratory distress syndrome patients (p < 0.001), and only 17.5% of pediatric acute respiratory distress syndrome patients discharged home without ongoing care versus 86.4% of patients without pediatric acute respiratory distress syndrome (adjusted relative risk, 1.5; 1.1-2.1). CONCLUSIONS Incidence and mortality associated with pediatric acute respiratory distress syndrome following traumatic injury are substantially higher than previously recognized, and pediatric acute respiratory distress syndrome development is associated with high risk of poor outcome even after adjustment for underlying injury type and severity.

Objectives To evaluate morbidity and mortality among critically injured children with acute respiratory distress syndrome. Design Retrospective cohort study. Setting Four-hundred sixty Level I/II adult or pediatric trauma centers contributing to the National Trauma Data Bank. Patients One hundred forty-six thousand fifty-eight patients less than 18 years old admitted to an ICU with traumatic injury from 2007 to 2016. Interventions None. Measurements and main results We assessed in-hospital mortality and need for postdischarge care among patients with and without acute respiratory distress syndrome and hospital resource utilization and discharge disposition among survivors. Analyses were adjusted for underlying mortality risk (age, Injury Severity Score, serious brain or chest injury, and admission heart rate and hypotension) and year, transfer status, and facility trauma level designation. Acute respiratory distress syndrome occurred in 2,590 patients (1.8%). Mortality was 20.0% among acute respiratory distress syndrome patients versus 4.3% among nonacute respiratory distress syndrome patients, with an adjusted relative risk of 1.76 (95% CI, 1.52-2.04). Postdischarge care was required in an additional 44.8% of acute respiratory distress syndrome patients versus 16.0% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.59; 2.87-4.49), with only 35.1% of acute respiratory distress syndrome patients discharging to home versus 79.8% of patients without acute respiratory distress syndrome. Acute respiratory distress syndrome mortality did not change over the 10-year study period (adjusted relative risk, 1.01/yr; 0.96-1.06) nor did the proportion of acute respiratory distress syndrome patients requiring postdischarge care (adjusted relative risk, 1.04/yr; 0.97-1.11). Duration of ventilation, ICU stay, and hospital stay were all significantly longer among acute respiratory distress syndrome survivors. Tracheostomy placement occurred in 18.4% of acute respiratory distress syndrome survivors versus 2.1% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.10; 2.59-3.70). Conclusions Acute respiratory distress syndrome development following traumatic injury in children is associated with significantly increased risk of morbidity and mortality, even after adjustment for injury severity and hemodynamic abnormalities. Outcomes have not improved over the past decade, emphasizing the need for new therapeutic interventions, and prevention strategies for acute respiratory distress syndrome among severely injured children.

To determine risk factors identifiable at hospital arrival associated with acute respiratory distress syndrome development among critically injured children.Retrospective cohort study.Level I or II adult or pediatric trauma centers contributing to the National Trauma Data Bank from 2007 to 2016.Patients less than 18 years admitted to an ICU with traumatic injury.None.We determined associations between patient, injury, and clinical characteristics present at hospital arrival with development of acute respiratory distress syndrome recorded as a hospital complication. Acute respiratory distress syndrome occurred in 1.8% of 146,058 critically injured children (n = 2,590). The only demographic factor associated with higher risk of developing acute respiratory distress syndrome on multivariable analysis was African American race (relative risk, 1.42 vs white; 95% CI, 1.13-1.78). Injury characteristics included firearm injuries (relative risk 1.93; 1.50-2.48) and motor vehicle crashes (relative risk, 1.91; 1.57-2.31) relative to falls; spine (relative risk, 1.39; 1.20-1.60), chest (relative risk, 1.36; 1.22-1.52), or lower extremity injuries (relative risk, 1.26; 1.10-1.44); amputations (relative risk, 2.10; 1.51-2.91); and more severe injury (relative risk, 3.69 for Injury Severity Score 40-75 vs 1-8; 2.50-5.44). Clinical variables included abnormal respiratory status (intubated relative risk, 1.67; 1.23-2.26 and hypopnea relative risk, 1.23; 1.05-1.45 and tachypnea relative risk, 1.26; 1.10-1.44) and lower Glasgow Coma Scale score (relative risk, 5.61 for Glasgow Coma Scale score 3 vs 15; 4.44-7.07).We provide the first description of the incidence of and risk factors for acute respiratory distress syndrome among pediatric trauma patients. Improved understanding of the risk factors associated with acute respiratory distress syndrome following pediatric trauma may help providers anticipate its development and intervene early to improve outcomes for severely injured children.

Long-term data are urgently needed in children after intensive care. The aim of this study was to measure health-related quality of life 6 years after intensive care in a paediatric intensive care population.This national, multicentre study enrolled all children and young people admitted to intensive care units (ICUs) in Finland in 2009 and 2010. The data concerning ICU stay were collected retrospectively from the ICU data registries and combined with prospective data from Paediatric Quality of Life Inventory (PedsQL 4.0) questionnaires, the generic 15D, 16D or 17D instrument, and data regarding children's chronic diagnoses and need for healthcare support.The questionnaires were answered by 1109 of 3682 living children and adolescents admitted to an ICU, response rate was 30.1%. Among the responders, 90 children (8.4%) had poor (under - 2 SD) PedsQL scores. Children with low scores had a higher rate of chronic diagnoses (94.4% vs. 47.6%), medication on a daily basis (78.7% vs. 29.4%) and a greater need for healthcare services (97.7% vs. 82.2%) than those with normal scores. Diagnoses associated with poor quality of life were asthma, epilepsy, cerebral palsy and other neurological diseases, chromosomal alterations, cancer and long-term pain. These children were mostly admitted electively, and less frequently on an emergency basis, but no other significant differences were found during the intensive care stay.The long-term quality of life after paediatric intensive care is good for the majority of children and young people, and it is dependent on the number of chronic diagnoses and the burden of the chronic disease, especially neurological diseases.

Clostridium septicum is an anaerobic bacterium that causes rapidly progressive myonecrosis, bacteremia, and central nervous system infection. It has been reported as a complication of Escherichia coli hemolytic uremic syndrome (HUS) in 8 children worldwide; 5 children died, and the 3 reported survivors had surgically treated disease. We present 3 cases of C septicum complicating HUS in children, including the first 2 reported cases of survival without surgical intervention. All patients presented with classic cases of HUS with initial clinical improvement followed by deterioration. Patient 1 had rising fever, tachycardia, and severe abdominal pain 24 hours after admission. She developed large multifocal intraparenchymal cerebral hemorrhages and died 12 hours later. Autopsy revealed C septicum intestinal necrosis, myonecrosis, and encephalitis. Patient 2 had new fever, increasing leukocytosis, and severe abdominal pain on hospital day 4. She was diagnosed with C septicum bacteremia and treated with metronidazole, meropenem, and clindamycin. Patient 3 had new fever and increasing leukocytosis on hospital day 3; blood cultures grew C septicum, and she was treated with penicillin. Patients 2 and 3 improved rapidly and did not require surgery. C septicum is a potential co-infection with E coli. It thrives in the anaerobic environment of E coli–damaged intestinal mucosa and translocates to cause systemic infection. Fever, tachycardia, a rising white blood cell count, and abdominal pain out of proportion to examination are key findings for which physicians should be vigilant. Timely evaluation by anaerobic blood culture and early initiation of antibiotics are necessary to prevent fatalities.

Key Points Question Is end-tidal carbon dioxide (EtCO2) a reliable surrogate for partial pressure of carbon dioxide, arterial (Paco2) in children admitted to the intensive care unit with traumatic brain injury? Findings In this secondary analysis of a prospective cohort study that included 445 paired Paco2-EtCO2 values from 137 patients, only 42.0% of Paco2 values were within 0 to 5 mm Hg of paired EtCO2 values. Development of pediatric acute respiratory distress syndrome within 24 hours after admission was associated with significantly lower likelihood of Paco2-EtCO2 agreement than was no development of pediatric acute respiratory distress syndrome. Meaning This study suggests that EtCO2 values are not a reliable substitute for Paco2 values during the first 24 hours after pediatric traumatic brain injury, especially in the presence of pediatric acute respiratory distress syndrome., Importance Alterations in the partial pressure of carbon dioxide, arterial (Paco2) can affect cerebral perfusion after traumatic brain injury. End-tidal carbon dioxide (EtCO2) monitoring is a noninvasive tool used to estimate Paco2 values. Objective To examine the agreement between Paco2 and EtCO2 and associated factors in children with traumatic brain injury. Design, Setting, and Participants A secondary analysis was conducted using data from a prospective cohort study of 137 patients younger than 18 years with traumatic brain injury who were admitted to the pediatric intensive care unit of a level I trauma center between May 1, 2011, and July 31, 2017. Analysis was performed from December 17, 2018, to January 10, 2019. Main Outcomes and Measures The closest EtCO2 value obtained within 30 minutes of a Paco2 value and the closest systolic blood pressure value obtained within 60 minutes prior to a Paco2 value during the first 24 hours after admission were recorded. The main outcome of Paco2-EtCO2 agreement was defined as Paco2 between 0 and 5 mm Hg greater than the paired EtCO2 value, and it was determined using Bland-Altman analysis, Passing and Bablok regression, and the Pearson correlation coefficient. Multivariable regression models determined which factors were associated with agreement. Results The analysis included 137 patients (34 girls and 103 boys; mean [SD] age, 10.0 [6.3] years) and 445 paired Paco2-EtCO2 data points. On average, Paco2 was 2.7 mm Hg (95% limits of agreement, –11.3 to 16.7) higher than EtCO2. Overall, 187 of all Paco2-EtCO2 pairs (42.0%) agreed. There was larger variation in the Paco2-EtCO2 difference during the first 8 hours compared with 9 to 24 hours after admission to the pediatric intensive care unit. Development of pediatric acute respiratory distress syndrome within 24 hours of admission was associated with a lower likelihood of Paco2-EtCO2 agreement (adjusted odds ratio, 0.20; 95% CI, 0.08-0.51) compared with no development of pediatric acute respiratory distress syndrome. A diagnosis of pediatric acute respiratory distress syndrome 1 to 7 days after admission was associated with a larger first-day Paco2-EtCO2 difference compared with those who never developed pediatric acute respiratory distress syndrome (mean [SD] difference, 4.48 [3.70] vs 0.46 [5.50] mm Hg). Conclusions and Relevance In this study of pediatric traumatic brain injury, Paco2-EtCO2 agreement was low, especially among patients with pediatric acute respiratory distress syndrome. Low Paco2-EtCO2 agreement early in hospitalization may be associated with future development of pediatric acute respiratory distress syndrome. Data on EtCO2 should not be substituted for data on Paco2 during the first 24 hours., This secondary analysis of a cohort study examines agreement between partial pressure of carbon dioxide, arterial (Paco2) and end-tidal carbon dioxide (EtCO2) and associated factors in children with traumatic brain injury (TBI).

The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alpha-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally.