Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity.

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

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.

Association of minor electrocardiographic (ECG) abnormalities with epilepsy duration in children: A manifestation of the epileptic heart?

PURPOSE: Cardiac abnormalities resulting from chronic epilepsy ("the epileptic heart") constitute a well-recognized comorbidity. However, the association of cardiac alterations with epilepsy duration remains understudied. We sought to evaluate this association using electrocardiogram (ECG). METHODS: We prospectively enrolled children between 1 months and 18 years of age without known cardiac conditions or ion channelopathies during routine clinic visits. ECGs were categorized as abnormal if there were alterations in rhythm; PR, QRS, or corrected QT interval; QRS axis or morphology; ST segment or T wave. An independent association between ECG abnormalities and epilepsy duration was evaluated using multivariable logistic regression modeling. RESULTS: 213 children were enrolled. 100 ECGs (47%) exhibited at least one alteration; most commonly in the ST segment (37, 17%) and T wave (29, 11%). Children with normal ECGs had shorter epilepsy duration as compared to those with ECG abnormalities (46 [18-91] months vs. 73 [32-128 months], p = 0.004). A multivariable logistic regression model demonstrated that increasing epilepsy duration was independently associated with the presence of ECG abnormalities (OR=1.09, 95% CI=1.02-1.16, p = 0.008), adjusted for seizure frequency, generalized tonic-clonic/focal to bilateral tonic-clonic seizures as the predominant seizure type, and number of channel-modifying anti-seizure medications. Increasing epilepsy duration was also independently associated with the presence of ST/T wave abnormalities (OR=1.09, 95% CI=1.01-1.16, p = 0.017), adjusted for the same covariates. SIGNIFICANCE: Increasing epilepsy duration is independently associated with the presence of minor ECG abnormalities. Additional studies are needed to evaluate whether this finding may represent a manifestation of the "epileptic heart".

"I Didn't Realize How Hard It Was Going to Be Just Transitioning Back into Life": A Qualitative Exploration of Outcomes for Survivors of Pediatric Septic Shock.

Recovery following pediatric critical illness is multifaceted and complex. While most critically ill children survive, many experience morbidities in physical, emotional, cognitive, and social function. We aimed to deeply explore and describe the multidimensional impact of pediatric septic shock for affected children and their families at the granular level using exploratory qualitative methodology. We performed semistructured telephone interviews of adolescents and caregivers of children admitted with community-acquired septic shock to two tertiary pediatric intensive care units in the United States. Interviews were conducted within two years of hospital admission, and were recorded, transcribed, and analyzed using thematic analysis. Two adolescents and 10 caregivers were interviewed. Participants described meaningful and long-lasting outcomes of septic shock on multiple dimensions of their lives. The adolescents and caregivers described substantial negative consequences on physical health and function which resulted in increased medical complexity and heightened caregiver vigilance. The physical impact led to substantial psychosocial consequences for both the child and family, including social isolation. Most caregivers expressed that septic shock was transformational in their lives, with some caregivers describing posttraumatic growth. This preliminary study provides a novel, granular view of the multidimensional impact of septic shock in pediatric patients and their families. Exploring these experiences through qualitative methodology provides greater insight into important patient and family outcomes. Deeper understanding of these outcomes may support the development of meaningful interventions to improve quality of life for children and their families following critical illness.

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

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

Reducing Time to Electroencephalography in Pediatric Convulsive Status Epilepticus: A Quality Improvement Initiative.

BACKGROUND: Pediatric convulsive status epilepticus (CSE) is a neurological emergency utilizing electroencephalography (EEG) to guide therapeutic interventions. Guidelines recommend EEG initiation within one hour of seizure onset, but logistic and structural barriers often lead to significant delays. We aimed to reduce the time to EEG in pediatric CSE. METHODS: From 2017 to 2022, we implemented process improvements, including EEG order sets with priority-based timing guidance, technologist workflow changes, a satisfaction survey, and feedback from key stakeholder groups, over five plan-do-study-act (PDSA) cycles. Seizure start time, time of EEG order, and time to EEG initiation were extracted. Time to interpretable EEG was determined from manual review of the EEG tracing. RESULTS: Time from EEG order to interpretable EEG decreased by nearly 50%, from a median of 90 minutes to 48 minutes. There were clinically and statistically significant improvements in time from EEG order to EEG initiation, time from EEG order to interpretable EEG, and EEG start to interpretable EEG. Ongoing provider education and guidance enabled improvements, whereas a new electronic health care record negatively impacted electronic ordering. EEG technologists reported that they understood the importance of emergent EEG for clinical care and did not find that the new workflow caused excessive disruption. CONCLUSIONS: Timely access to EEG for pediatric patients with CSE can be improved through clinical processes that use existing devices and that maintain the benefits of full-montage EEG recordings. Similar process improvement efforts may be generalizable to other institutions to increase adherence to guidelines and provide improved care.

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.

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.

Pediatric Critical Care Outcomes: State of the Science.

Children who survive the pediatric intensive care unit (PICU) are at risk of developing post-intensive care syndrome in pediatrics (PICS-p). PICS-p, defined as new physical, cognitive, emotional, and/or social health dysfunction following critical illness, can affect the child and family. Historically, synthesizing PICU outcomes research has been challenging due to inconsistency in study design and in outcomes measurement. PICS-p risk may be mitigated by implementing intensive care unit best practices that limit iatrogenic injury and by supporting the resiliency of critically ill children and their families.

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.

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.

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.

Sleep Architecture in Mechanically Ventilated Pediatric ICU Patients Receiving Goal-Directed, Dexmedetomidine- and Opioid-based Sedation.

This single-center prospective observational study aimed to evaluate sleep architecture in mechanically ventilated pediatric intensive care unit (PICU) patients receiving protocolized light sedation. We enrolled 18 children, 6 months to 17 years of age, receiving mechanical ventilation and standard, protocolized sedation for acute respiratory failure, and monitored them with 24 hours of limited (10 channels) polysomnogram (PSG). The PSG was scored by a sleep technician and reviewed by a pediatric sleep medicine physician. Sixteen children had adequate PSG data for sleep stage scoring. All received continuous opioid infusions, 15 (94%) received dexmedetomidine, and 7 (44%) received intermittent benzodiazepines. Total sleep time was above the age-matched normal reference range (median 867 vs. 641 minutes, p = 0.002), attributable to increased stage N1 and N2 sleep. Diurnal variation was absent, with a median of 47% of sleep occurring during night-time hours. Rapid eye movement (REM) sleep was observed as absent in most patients ( n = 12, 75%). Sleep was substantially disrupted, with more awakenings per hour than normal for age (median 2.2 vs. 1.1, p = 0.008), resulting in a median average sleep period duration (sleep before awakening) of only 25 minutes (interquartile range [IQR]: 14-36) versus normal 72 minutes (IQR: 65-86, p = 0.001). Higher ketamine and propofol doses were associated with increased sleep disruption. Children receiving targeted, opioid-, and dexmedetomidine-based sedation to facilitate mechanical ventilation for acute respiratory failure have substantial sleep disruption and abnormal sleep architecture, achieving little to no REM sleep. Dexmedetomidine-based sedation does not ensure quality sleep in this population.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

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

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.

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.

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.

Actigraphy in mechanically ventilated pediatric ICU patients: comparison to PSG and evaluation of behavioral circadian rhythmicity.

Sleep disruption is common in pediatric intensive care unit (PICU) patients, but measuring sleep in this population is challenging. We aimed to evaluate the utility of actigraphy for estimating circadian rhythmicity in mechanically ventilated PICU patients and its accuracy for measuring sleep by comparing it to polysomnogram (PSG). We conducted a single-center prospective observational study of children 6 months - 17 years of age receiving mechanical ventilation and standard, protocolized sedation for acute respiratory failure, excluding children with acute or historical neurologic injury. We enrolled 16 children and monitored them with up to 14 days of actigraphy and 24 hours of simultaneous limited (10 channel) PSG. Daily actigraphy-based activity profiles demonstrated that patients had a high level of nighttime activity (30-41% of total activity), suggesting disrupted circadian activity cycles. Among n = 12 patients with sufficient actigraphy and PSG data overlap, actigraphy-based sleep estimation showed poor agreement with PSG-identified sleep states, with good sensitivity (94%) but poor specificity (28%), low accuracy (70%,) and low agreement (Cohen's kappa = 0.2, 95% CI = 0.08-0.31). Using univariate linear regression, we identified that Cornell Assessment of Pediatric Delirium scores were associated with accuracy of actigraphy but that other clinical factors including sedative medication doses, activity levels, and restraint use were not. In this population, actigraphy did not reliably discern between sleep and wake states. However, in select patients, actigraphy was able to distinguish diurnal variation in activity patterns, and therefore may be useful for evaluating patients' response to circadian-oriented interventions.