Barriers to Implementing the ICU Liberation Bundle in a Single-center Pediatric and Cardiac ICUs.

Objectives: The intensive care unit (ICU) Liberation "ABCDEF" Bundle improves outcomes in critically ill adults. We aimed to identify common barriers to Pediatric ICU Liberation Bundle element implementation, to describe differences in barrier perception by ICU staff role, and to describe changes in reported barriers over time. Study Design: A 91-item survey was developed based on existing literature, iteratively revised, and tested by the PICU Liberation Committee at Seattle Children's Hospital, a tertiary free-standing academic children's hospital. Voluntary surveys were administered electronically to all ICU staff twice over 4-week periods in 2017 and 2020. Survey Respondents: 119 (2017) and 163 (2020) pediatric and cardiac ICU staff, including nurses (n = 142, 50%), respiratory therapists (RTs) (n = 46, 16%), attending and fellow physicians, hospitalists, and advanced practice providers (APPs) (n = 62, 22%), physical, occupational, and speech-language pathology therapists (n = 25, 9%), and pharmacists (n = 7, 2%). Measurements and Main Results: Respondents widely agreed that increased workload (78%-100% across roles), communication (53%-84%), and lack of RT-directed ventilator weaning (68%-88%) are barriers to implementation. Other barriers differed by role. In 2020, nurses reported liability (59%) and personal injury (68%) concerns, patient severity of illness (24%), and family discomfort with ICU liberation practices (41%) more frequently than physicians and APPs (16%, 6%, 8%, and 19%, respectively; P < .01 for all). Between 2017 and 2020, some barriers changed: RTs endorsed discomfort with early mobilization less frequently (50% vs 11%, P = .028) and nurses reported concern for patient harm less frequently (51% vs 24%, P = .004). Conclusions: Implementation efforts aimed at addressing known barriers, including educating staff on the safety of early mobility, considering respiratory therapist-directed ventilator weaning, and standardizing interdisciplinary discussion of Pediatric ICU Liberation Bundle elements, will be needed to overcome barriers and improve ICU Liberation Bundle implementation.

Pediatric Acute Respiratory Distress Syndrome Severity and Health-Related Quality of Life Outcomes: Single-Center Retrospective Cohort, 2011-2017.

OBJECTIVES: To determine factors associated with health-related quality of life (HRQL) decline among pediatric acute respiratory distress syndrome (PARDS) survivors. DESIGN: Retrospective cohort study. SETTING: Academic children's hospital. PATIENTS: Three hundred fifteen children 1 month to 18 years old with an unplanned PICU admission from December 2011 to February 2017 enrolled in the hospital's Outcomes Assessment Program. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pre-admission baseline and median 6-week post-discharge HRQL were assessed using the Pediatric Quality of Life Inventory or the Functional Status II-R. Patients meeting retrospectively applied Second Pediatric Acute Lung Injury Consensus Conference criteria for PARDS were identified, and PARDS severity was classified using binary (mild/moderate, severe) and trichotomous (mild, moderate, severe) categorization for noninvasive ventilation and invasive mechanical ventilation (IMV). PARDS occurred in 41 of 315 children (13.0%). Clinically important HRQL decline (≥ 4.5 points) occurred in 17 of 41 patients (41.5%) with PARDS and 64 of 274 without PARDS (23.4%). On multivariable generalized linear regression adjusted for age, baseline Pediatric Overall Performance Category, maximum nonrespiratory Pediatric Logistic Organ Dysfunction score, diagnosis, length of stay, and time to follow-up, PARDS was associated with HRQL decline (adjusted relative risk [aRR], 1.70; 95% CI, 1.03-2.77). Four-hour and maximum PARDS severity were the only factors associated with HRQL decline. HRQL decline occurred in five of 18 patients with mild PARDS at 4 hours, five of 13 with moderate PARDS (aRR 2.35 vs. no PARDS [95% CI, 1.01-5.50]), and seven of ten with severe PARDS (aRR 2.56 vs. no PARDS [95% CI, 1.45-4.53]). The area under the receiver operating characteristic curve for discrimination of HRQL decline for IMV patients was 0.79 (95% CI, 0.66-0.91) for binary and 0.80 (95% CI, 0.69-0.93) for trichotomous severity categorization. CONCLUSIONS: HRQL decline is common among children surviving PARDS, and risk of decline is associated with PARDS severity. HRQL decline from baseline may be an efficient and clinically meaningful endpoint to incorporate into PARDS clinical trials.

Social Determinants of Health and Health-Related Quality of Life Following Pediatric Septic Shock: Secondary Analysis of the Life After Pediatric Sepsis Evaluation Dataset, 2014-2017.

OBJECTIVES: Social determinants of health (SDOH) are associated with disparities in disease severity and in-hospital outcomes among critically ill children. It is unknown whether SDOH are associated with later outcomes. We evaluated associations between SDOH measures and mortality, new functional morbidity, and health-related quality of life (HRQL) decline among children surviving septic shock. DESIGN: Secondary analysis of the Life After Pediatric Sepsis Evaluation (LAPSE) prospective cohort study was conducted between 2014 and 2017. SETTING: Twelve academic U.S. PICUs were involved in the study. PATIENTS: Children younger than 18 years with community-acquired septic shock were involved in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed associations between race, ethnicity, income, education, marital status, insurance, language, and home U.S. postal code with day 28 mortality, new functional morbidity at discharge per day 28, and HRQL decline using logistic regression. Of 389 patients, 32% ( n = 98) of families had household income less than $50,000 per year. Median Pediatric Risk of Mortality (PRISM) score was 11 (interquartile range 6, 17). We found that English language and Area Deprivation Index less than 50th percentile were associated with higher PRISM scores. Mortality was 6.7% ( n = 26), new functional morbidity occurred in 21.8% ( n = 78) of patients, and HRQL decline by greater than 10% occurred in 31.0% of patients ( n = 63). We failed to identify any association between SDOH measures and mortality, new functional morbidity, or HRQL decline. We are unable to exclude the possibility that annual household income greater than or equal to $50,000 was associated with up to 81% lesser odds of mortality and, in survivors, more than three-fold greater odds of HRQL decline by greater than 10%. CONCLUSIONS: In this secondary analysis of the 2014-2017 LAPSE dataset, we failed to identify any association between SDOH measures and in-hospital or postdischarge outcomes following pediatric septic shock. This finding may be reflective of the high illness severity and single disease (sepsis) of the cohort, with contribution of clinical factors to functional and HRQL outcomes predominating over prehospital and posthospital SDOH factors.

Measuring Social Health Following Pediatric Critical Illness: A Scoping Review and Conceptual Framework.

OBJECTIVE: Social health is an important component of recovery following critical illness as modeled in the pediatric Post-Intensive Care Syndrome framework. We conducted a scoping review of studies measuring social outcomes (measurable components of social health) following pediatric critical illness and propose a conceptual framework of the social outcomes measured in these studies. DATA SOURCES: PubMed, EMBASE, PsycINFO, CINAHL, and the Cochrane Registry. STUDY SELECTION: We identified studies evaluating social outcomes in pediatric intensive care unit (PICU) survivors or their families from 1970-2017 as part of a broader scoping review of outcomes after pediatric critical illness. DATA EXTRACTION: We identified articles by dual review and dual-extracted study characteristics, instruments, and instrument validation and administration information. For instruments used in studies evaluating a social outcome, we collected instrument content and described it using qualitative methods adapted to a scoping review. DATA SYNTHESIS: Of 407 articles identified in the scoping review, 223 (55%) evaluated a social outcome. The majority were conducted in North America and the United Kingdom, with wide variation in methodology and population. Among these studies, 38 unique instruments were used to evaluate a social outcome. Specific social outcomes measured included individual (independence, attachment, empathy, social behaviors, social cognition, and social interest), environmental (community perceptions and environment), and network (activities and relationships) characteristics, together with school and family outcomes. While many instruments assessed more than one social outcome, no instrument evaluated all areas of social outcome. CONCLUSIONS: The full range of social outcomes reported following pediatric critical illness were not captured by any single instrument. The lack of a comprehensive instrument focused on social outcomes may contribute to under-appreciation of the importance of social outcomes and their under-representation in PICU outcomes research. A more comprehensive evaluation of social outcomes will improve understanding of overall recovery following pediatric critical illness.

Risk Factors for Positive Post-Traumatic Stress Disorder Screening and Associated Outcomes in Children Surviving Acute Respiratory Failure: A Secondary Analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure Clinical Trial.

OBJECTIVES: To identify risk factors and outcomes associated with a positive post-traumatic stress disorder (PTSD) screen following pediatric acute respiratory failure treated with invasive mechanical ventilation. DESIGN: Nonprespecified secondary analysis of a randomized clinical trial. SETTING: Thirty-one U.S. PICUs. PATIENTS: Children in the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial (NCT00814099, ClinicalTrials.gov ) over 8 years old who completed PTSD screening 6 months after discharge. INTERVENTIONS: RESTORE sites were randomized to a targeted, nurse-directed sedation strategy versus usual care. MEASUREMENTS AND MAIN RESULTS: PTSD screening was completed by 102 subjects using the Child Post-Traumatic Stress Disorder Symptom Scale; a score of greater than or equal to 11 was considered screening positive for PTSD. Cognitive status was categorized using Pediatric Cerebral Performance Category; health-related quality of life (HRQL) was evaluated using child-reported Pediatric Quality of Life Inventory, Version 4.0. Thirty-one children (30%) screened positive for PTSD. Children with a positive screen endorsed symptoms in all categories: reexperiencing, avoidance, and hyperarousal. Most endorsed that symptoms interfered with schoolwork ( n = 18, 58%) and happiness ( n = 17, 55%). Screening positive was not associated with RESTORE treatment group. In a multivariable logistic model adjusting for age, sex, and treatment group, screening positive was independently associated with lower median income in the family's residential zip code (compared with income ≥ $80,000; income < $40,000 odds ratio [OR], 32.8; 95% CI, 2.3-458.1 and $40,000-$79,999 OR, 15.6; 95% CI, 1.3-182.8), renal dysfunction (OR 5.3, 95% CI 1.7-16.7), and clinically significant pain in the PICU (OR, 8.3; 95% CI, 1.9-35.7). Children with a positive screen experienced decline in cognitive function and impaired HRQL more frequently than children with a negative screen. CONCLUSIONS: Screening positive for PTSD is common among children following acute respiratory failure and is associated with lower HRQL and decline in cognitive function. Routine PTSD screening may be warranted to optimize recovery.

Family Presence at the PICU Bedside: A Single-Center Retrospective Cohort Study.

OBJECTIVES: To determine factors associated with bedside family presence in the PICU and to understand how individual factors interact as barriers to family presence. DESIGN: Mixed methods study. SETTING: Tertiary children's hospital PICU. SUBJECTS: Five hundred twenty-three children of less than 18 years enrolled in the Seattle Children's Hospital Outcomes Assessment Program from 2011 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Quantitative: Family was documented every 2 hours. Exposures included patient and illness characteristics and family demographic and socioeconomic characteristics. We used multivariable logistic regression to identify factors associated with presence of less than 80% and stratified results by self-reported race. Longer PICU length of stay (LOS), public insurance, and complex chronic conditions (C-CD) were associated with family presence of less than 80%. Self-reported race modified these associations; no factors were associated with lower bedside presence for White families, in contrast with multiple associations for non-White families including public insurance, C-CD, and longer LOS. Qualitative: Thematic analysis of social work notes for the 48 patients with family presence of less than 80% matched on age, LOS, and diagnosis to 48 patients with greater than or equal to 95% family presence. Three themes emerged: the primary caregiver's prior experiences with the hospital, relationships outside of the hospital, and additional stressors during the hospitalization affected bedside presence. CONCLUSIONS: We identified sociodemographic and illness factors associated with family bedside presence in the PICU. Self-reported race modified these associations, representing racism within healthcare. Family presence at the bedside may help identify families facing greater disparities in healthcare access.

Components of Health-Related Quality of Life Most Affected Following Pediatric Critical Illness.

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-relatedquality 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.

Delirium in a Tertiary Pediatric Cardiac Intensive Care Unit: Risk Factors and Outcomes.

OBJECTIVE: Delirium is an increasingly recognized hospital complication associated with poorer outcomes in critically ill children. We aimed to evaluate risk factors for screening positive for delirium in children admitted to a pediatric cardiac intensive care unit (CICU) and to examine the association between duration of positive screening and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study in a single-center quaternary pediatric hospital CICU evaluating children admitted from March 2014-October 2016 and screened for delirium using the Cornell Assessment of Pediatric Delirium. Statistical analysis used multivariable logistic and linear regression. RESULTS: Among 942 patients with screening data (98% of all admissions), 67% of patients screened positive for delirium. On univariate analysis, screening positive was associated with younger age, single ventricle anatomy, duration of mechanical ventilation, continuous renal replacement therapy, extracorporeal life support, and surgical complexity, as well as higher average total daily doses of benzodiazepines, opioids, and dexmedetomidine. On multivariable analysis, screening positive for delirium was independently associated with age <2 years, duration of mechanical ventilation, and greater than the median daily doses of benzodiazepine and opioid. In addition to these factors, duration of screening positive was also independently associated with higher STAT category (3-5) or medical admission, organ failure, acute kidney injury (AKI), and higher dexmedetomidine exposure. Duration of positive delirium screening was associated with both increased CICU and hospital length of stay (each additional day of positive screening was associated with a 3% longer CICU stay [95% CI = 1%-6%] and 2% longer hospital stay [95% CI = 0%-4%]). CONCLUSIONS: Screening positive for delirium is common in the pediatric CICU and is independently associated with prolonged intensive care unit (ICU) and hospital stay. Longer duration of mechanical ventilation and higher sedative doses are independent risk factors for screening positive for delirium. Efforts aimed at reducing these exposures may decrease the burden of delirium in this population.

Health-Related Quality of Life Following Delirium in the PICU.

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.

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.

The association of severe pain experienced in the pediatric intensive care unit and postdischarge health-related quality of life: A retrospective cohort study.

BACKGROUND: Pain may be a modifiable risk factor for lower health-related quality of life after pediatric critical illness. AIM: To evaluate the association between severe pain experienced in the (pediatrc intensive care unit) and postdischarge health-related quality of life. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Overall Health Following Pediatric Critical Illness: A Scoping Review of Instruments and Methodology.

OBJECTIVES: Families identify overall health as a key outcome after pediatric critical illness. We conducted a planned secondary analysis of a scoping review to determine the methods, populations, and instruments used to evaluate overall health outcomes for both children and their families after critical illness. DESIGN: Planned Secondary Analysis of a Scoping Review. SETTING: We searched PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Controlled Trials Registry databases from 1970 to 2017 to identify studies which measured postdischarge overall health of children who survived critical illness and their families. SUBJECTS: Articles reporting overall health outcomes after pediatric critical illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 407 articles which measured outcomes following pediatric critical illness, 161 (40%) measured overall health. The overall health domain was most commonly measured in traumatic brain injury (44%) and the general PICU populations (16%). In total, there were 39 unique measures used to evaluate overall health. Across all subjects, seven measures accounted for 89% of instruments, with the Glasgow Outcome Scale (47%) and the Pediatric Overall Performance Category (17%) being most commonly used. Excluding studies targeting survivors of traumatic brain injury, Pediatric Overall Performance Category, Glasgow Outcome Scale, and the General Health Questionnaire were the most commonly used instruments. Patients were followed for a median 10.5 months (interquartile range, 4.5-21 mo). CONCLUSIONS: Overall health was commonly assessed post-PICU discharge, especially in the traumatic brain injury population, using a heterogenous array of measures. Evaluation and consensus are imperative to identify the most appropriate method to measure overall health with the goal of improving care efficacy and facilitating recovery across populations of critically ill children.

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.

Delirium in a Tertiary PICU: Risk Factors and Outcomes.

OBJECTIVES: To determine risk factors and outcomes associated with delirium in PICU patients. DESIGN: Retrospective cohort study. SETTING: Thirty-two-bed PICU within a tertiary care academic children's hospital. PATIENTS: All children admitted to the PICU March 1, 2014, to October 1, 2016, with at least one Cornell Assessment of Pediatric Delirium score (n = 2,446). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cornell Assessment of Pediatric Delirium score was performed twice daily as standard of care. We characterized delirium as: 1) presence of greater than or equal to 1 positive score (Cornell Assessment of Pediatric Delirium ≥ 9) and 2) number of days with a positive score. We built multivariable logistic and linear regression models using electronic medical records data. Many patients (n = 1,538; 63%) had a short length of stay (< 48 hr). Compared with patients with length of stay greater than or equal to 48 hours, fewer experienced delirium (30% vs 69%; p < 0.0001). Among 908 patients with length of stay greater than or equal to 48 hours, presence of delirium was independently associated with age less than 2 years old, baseline cognitive dysfunction, primary diagnosis, and duration of mechanical ventilation. Benzodiazepines demonstrated a dose-response effect (odds ratio for presence of delirium, 1.8 [p = 0.03], 3.4 [p < 0.001], and 9.7 [p = 0.005] for < 25th percentile, 25-75th percentile, and > 75th percentile of total dose, vs no exposure). In terms of outcomes, presence of delirium was independently associated with increased ICU length of stay (p < 0.001), whereas days of delirium were independently associated with decline in cognitive function from ICU admission to discharge (odds ratio, 1.06; p < 0.001), increased ICU (p < 0.001), and hospital length of stay (p < 0.001). Neither delirium presence nor total days were independently associated with mortality. CONCLUSIONS: Delirium is common in the PICU, particularly among patients with length of stay greater than or equal to 48 hours. It is independently associated with patient characteristics and PICU exposures, including benzodiazepines. The role of delirium as an independent causal factor in patient outcome requires further investigation.

Health-Related Quality of Life Among Survivors of Pediatric Sepsis.

OBJECTIVES: 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. DESIGN: Retrospective cohort study. SETTING: Seattle Children's Hospital. PATIENTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

Long-Term Outcomes after Protocolized Sedation versus Usual Care in Ventilated Pediatric Patients.

RATIONALE: Whether a nurse-implemented goal-directed sedation protocol resulting in more awake yet calm intubated children affects postdischarge functional status, health-related quality of life, or risk for post-traumatic stress disorder is unknown. OBJECTIVES: To compare postdischarge outcomes in children with acute respiratory failure cluster-randomized to a sedation protocol or usual care. METHODS: A stratified random sample of 1,360 patients from 31 centers in the RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) trial was assessed by mail, electronically, and/or telephone 6 months after ICU discharge. In treatment group comparisons, we controlled for age, baseline functional status, and severity of illness. MEASUREMENTS AND MAIN RESULTS: We used the Pediatric Overall Performance Category and the Pediatric Cerebral Performance Category to characterize functional status, the Infant and Toddler Quality of Life Questionnaire (97-item full-length version) (<2 yr old) or Pediatric Quality of Life Inventory (≥2 yr old), and the Child Post-traumatic Stress Disorder Symptom Scale (≥8 yr old and developmentally able). Functional status worsened from baseline to follow-up in 20%. Decline in functional status did not differ by treatment arm and was more common among those with baseline impairment than those with baseline normal function (27 vs. 18%; P < 0.001). There were no significant differences in health-related quality of life total scores by treatment arm. Scores indicating risk of post-traumatic stress disorder occurred in 30%, with no difference between treatment arms. CONCLUSIONS: A sedation strategy that allows patients to be more awake and exposes them to fewer sedative and analgesic medications produces no long-term harm. However, postdischarge morbidity after acute respiratory failure is common. Clinical trial registered with www.clinicaltrials.gov (NCT00814099).

Delirium in Critically Ill Children: An International Point Prevalence Study.

OBJECTIVES: To determine prevalence of delirium in critically ill children and explore associated risk factors. DESIGN: Multi-institutional point prevalence study. SETTING: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. PATIENTS: All children admitted to the pediatric critical care units on designated study days (n = 994). INTERVENTION: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. MEASUREMENTS AND MAIN RESULTS: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics. CONCLUSIONS: Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units.

The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic review of the literature and meta-analysis.

BACKGROUND: Continuous opioid infusion therapy is commonly utilized in the pediatric intensive care setting to treat pain and facilitate tolerance of invasive therapies. Transitioning to methadone is one common strategy for weaning from continuous opioid infusions, but in practice this transition can be challenging, and many children still experience iatrogenic withdrawal. AIM: We reviewed the literature to evaluate the best available evidence to guide methadone therapy in this setting, and to summarize associated adverse events. METHODS: We included all studies of methadone used to facilitate weaning from continuous opioid infusions in pediatric critical care patients, including medical, cardiac, and surgical patients, excluding case reports and studies treating neonatal abstinence syndrome, or acute or chronic pain. Medline, Embase, and CINAHL databases from inception to May 2015 were queried; references of included works and conference proceedings were also reviewed. Two authors independently extracted data from each study. Meta-analysis with fixed- and random-effects models was used to pool results of studies when applicable. RESULTS: Twelve studies involving 459 patients met criteria for inclusion. A wide variety of methadone dosing and taper strategies were reported. Mean inpatient methadone taper times varied widely, from 4.3 to 26.2 days. Excessive sedation was the most frequently reported adverse event, occurring in up to 16% of patients. Withdrawal occurred in 27% of patients among studies reporting this outcome. In three of three studies in which a new methadone protocol was introduced, a decreased proportion of patients experienced withdrawal (standardized mean difference, SMD = -0.60, 95% CI = -0.998 to -0.195, P = 0.004). CONCLUSION: We did not identify sufficient evidence to recommend any particular methadone weaning strategy, or to recommend methadone over other medications or prescribed infusion weaning, for successful weaning of continuous opioid infusions in the pediatric intensive care setting.

Risk of congenital heart defects in the offspring of smoking mothers: a population-based study.

OBJECTIVES: To conduct a population-based study examining the occurrence of congenital heart defects (CHDs) in relation to maternal smoking during the first trimester of pregnancy. STUDY DESIGN: This retrospective case-control study used Washington State birth certificates from 1989 to 2011 and linked hospital discharge International Classification of Diseases, 9th revision, codes to identify singleton nonsyndromic CHD cases and determine maternal prenatal smoking status. We calculated ORs from multivariate logistic regression models to compare maternal first-trimester smoking status (any and daily number of cigarettes) among 14,128 cases, both overall and by phenotype, and 60,938 randomly selected controls frequency matched on birth year. RESULTS: Offspring of mothers reporting cigarette use in the first trimester of pregnancy were more likely to be born with a CHD (aOR 1.16 [1.08-1.24]) independent of demographic characteristics and other prenatal risk factors for CHDs. Maternal smoking was most strongly associated with pulmonary valve anomalies (aOR 1.48 [95% CI: 1.15-1.90]), pulmonary artery anomalies (aOR 1.71 [1.40-2.09]), and isolated atrial septal defects (aOR 1.22 [1.08-1.38]). The association between maternal smoking and CHDs was stronger with increasing number of daily cigarettes and among older (35+ years) mothers compared with younger mothers. CONCLUSIONS: We provide evidence that maternal smoking during pregnancy is a risk factor for select CHD phenotypes. Maternal smoking may account for 1.4% of all CHDs. New findings include a strong dose-dependence of the association and augmented risk in older mothers.