Pediatric Intensive Care Unit Discharge Research Articles

Mortality following admission to the paediatric intensive care unit: A Swedish longitudinal cohort study.

This study aimed to compare outcomes post-admission to a Swedish paediatric intensive care unit (PICU) in children with complex chronic conditions (CCC) and without CCC. In this observational registry-based study, consecutive admissions to the Astrid Lindgren Children's Hospital PICU from 1 January 2008 to 31 December 2016 were analysed. Data on demographics, predicted death rates (PDR), admission diagnoses and causes of death were collected. Mortality was recorded up to 15 years after admission and compared between groups. Patients with CCC constituted 64.6% (n = 3026) of PICU admissions and 83.5% (n = 111) of PICU deaths. The crude mortality rate in PICU was 2.84% overall. CCC-patients were 2.83 times more likely to die in PICU compared to non-CCC (OR 2.83; 95% CI: 1.78-4.49). Mortality increased in the CCC-cohort up to 5 years after PICU discharge, while non-CCC patients generally survived if they survived in PICU. Of the patients who died in PICU, the median PDR was 22.9% for CCC-patients and 66.5% in the non-CCC cohort. Children with CCC accounted for most admissions and deaths in PICU. Despite lower severity of illness scores upon admission, CCC patients were nearly three times more likely to die in PICU compared to non-CCC patients.

Patient follow-up after discharge from the paediatric intensive care unit: A scoping review.

Most children admitted to a paediatric intensive care unit (PICU) now survive because of improvements in care. Many studies have identified the psychological, functional, cognitive and social impact of PICU admission on a child and their family. However, expert recommendations on follow-up are lacking. To identify the strategies of clinical follow-up after PICU discharge performed from 2001 to 2021. This scoping review was undertaken between January and April 2021 using three databases: PubMed, EMBASE and CINAHL. The search strategy consisted of a combination of keywords, including PICU, post-PICU discharge and follow-up in articles published between 2001 and 2021. The results are reported according to PRISMA-ScR guidelines. Six-hundred and fifty-two articles were identified and 68 were analysed. Median age was 4.5 years and the two main reasons for PICU admission were cardiorespiratory failure and sepsis. Median length of PICU stay was 8 days. Most follow-up was carried out by research units (88%), while 6% of studies reported follow-up by a multidisciplinary PICU team. The most common follow-up schedule included an assessment at PICU discharge, and then at 3, 6 and 12 months. Follow-up for >1 year was reported in 20% of studies. One third of studies focused on follow-up quality of life and neurological outcomes. Parental emotional impact was assessed in 7% of studies. Follow-up after PICU discharge was highly heterogeneous regarding timing, health care professionals involved and assessment methods. There is an urgent need for standardization and coordination of PICU follow-up because of the increasing number of patients impacted by a PICU stay. Although most patients admitted to a paediatric intensive care unit (PICU) now survive; they may develop paediatric post-intensive care syndrome (PICS-P). To our knowledge, there are currently no clinical guidelines regarding follow-up after PICU discharge. This review summarizes current approaches to follow-up after PICU discharge, including how it is carried out, who is involved and what the main aims of assessment are.

Predicting Parental Post-Traumatic Stress Symptoms Following their Child's Stay in a Pediatric Intensive Care Unit, Prior to Discharge.

Objective: Develop an inpatient predictive model of parental post-traumatic stress (PTS) following their child's care in the Pediatric Intensive Care Unit (PICU). Design: Prospective observational cohort. Setting: Two tertiary care children's hospitals with mixed medical/surgical/cardiac PICUs. Subjects: Parents of patients admitted to the PICU. Interventions: None. Measurements and Main Results: Preadmission and admission data from 169 parents of 129 children who completed follow up screening for parental post-traumatic stress symptoms at 3-9 months post PICU discharge were utilized to develop a predictive model estimating the risk of parental PTS 3-9 months after hospital discharge. The parent cohort was predominantly female (63%), partnered (75%), and working (70%). Child median age was 3 years (IQR 0.36-9.04), and more than half had chronic illnesses (56%) or previous ICU admissions (64%). Thirty-five percent (60/169) of parents met criteria for PTS (>9 on the Post-traumatic Stress Disorder Symptom Scale-Interview). The machine learning model (XGBoost) predicted subjects with parental PTS with 76.7% accuracy, had a sensitivity of 0.83 (95% CI 0.586, 0.964), a specificity of 0.72 (95% CI 0.506, 0.879), a precision of 0.682 (95% CI 0.451, 0.861) and number needed to evaluate of 1.47 (95% CI 1.16, 1.98). The area under the receiver operating curve was 0.78 (95% CI 0.64, 0.92). The most important predictive pre-admission and admission variables were determined using the Local Interpretable Model-Agnostic Explanation, which identified seven variables used 100% of the time. Composite variables of parental history of mental illness and traumatic experiences were most important. Conclusion: A machine learning model using parent risk factors predicted subsequent PTS at 3-9 months following their child's PICU discharge with an accuracy of 76.7% and number needed to evaluate of 1.47. This performance is sufficient to identify parents who are at risk during hospitalization, making inpatient and acute post admission mitigation initiatives possible.

Functional outcomes and clinical characteristics of children discharged from pediatric intensive care unit of a low- and middle-income countries: A single-center prospective observational cohort study from Rwand

Abstract Background: The development of pediatric intensive care units (PICUs) has contributed to the improvement in the survival of critically ill children; however, the long-term functional outcome of these children is often unknown in many low-/middle-income countries including Rwanda. This study aimed to describe incidence and type of long-term functional outcomes and associated clinical characteristics among PICU survivors during a 5 years’ period (2015–2019). Subjects and Methods: This was a single-center, prospective observational cohort study conducted in the PICU of University Teaching Hospital in Rwanda. A Pediatric Cerebral Performance Category (PCPC) and Pediatric Overall Performance Category (POPC) scales were used to screen for long-term functional outcomes. The results were evaluated by telephone interview and statistically analyzed using logistic regression. Results: Out of 158 children, 53.2% had overall disability while 33.6% had some level of cognitive disability after PICU discharge. Out of 41 (2`5.9%) deaths during study period, three (7.3%) occurred during the hospital stay, while 8 (19.6%) occurred after the first year of hospital discharge. Disability screened by two scales, PCPC and PCOC, was comparable for mild (13.3% vs. 23.4%), moderate (11.4% vs. 20.3%), and severe (5.1% vs. 5.7%) categories. PICU admission for patient with at least one preadmission comorbidity had significantly greater disability at discharge (P < 0.05). Conclusions: Despite a high survival rate, residual functional disability is prevalent among children after discharge from the PICU in Rwanda. The presence of at least one preadmission comorbidity was independently associated with greater disability at discharge.

Acute Kidney Injury in Relation to Nephrotoxic Medication Use Among Critically Ill Children in the Paediatric Intensive Care Unit.

Background: Critically ill children are vulnerable to acute kidney injury (AKI) and are often exposed to nephrotoxic medications. Objectives: We aimed to investigate the association between nephrotoxic medications and the risk of AKI in critically ill children admitted to our paediatric intensive care unit (PICU). Methods: Patients aged > 1 month to ≤18 years old were prospectively recruited from 6/2020 to 6/2021. The medication records from 14 days prior to PICU admission to PICU discharge were reviewed. Medication-exposure intensity was defined as the number of concomitant nephrotoxic medications. The relative risk (RR) of nephrotoxic medication exposure indices and other potential predictors for AKI development were determined. Results: Altogether 253 episodes of admissions (median [IQR] age of 4.9 [9.6] years) were enrolled. The AKI incidence was 41.9% and 69.2% of the patients were exposed to ≥1 of the 47 nephrotoxic medications. The total nephrotoxic medication dose (RR: 1.01 [1.00, 1.02]) and medication-exposure intensity (RR: 1.381 [1.101, 1.732]) were significantly associated with AKI development. The risk of AKI increased when the medication-exposure intensity was ≥4 (RR: 3.687 (1.320, 10.301)). During their PICU stay, children with AKI received a higher number (P < .01), total dose (P < .01) and medication exposure intensity (P < .01) of nephrotoxic medications. Children with AKI who received nephrotoxic medications were more likely to have a persistently higher peak-to-baseline ratio (P = .046). Conclusion: Nephrotoxic medication exposure significantly increased the risk of AKI development among critically ill children. The use of nephrotoxic medications among critically ill children at risk for AKI should be monitored frequently.

Physical, Cognitive, Emotional, and Social Health Outcomes of Parents in the First Six Months after Childhood Critical Illness: A Prospective Single Centre Study.

Childhood critical illness can have long-term effects on families, but the extent and trajectory of recovery for parents are unknown. Using prospective longitudinal design, we describe the health outcomes of parents and their trajectory six months after paediatric intensive care unit (PICU) discharge. Parents reported health outcomes at PICU discharge (baseline), and 1-, 3-, and 6-months post-discharge. We used the Pediatric Quality-of-Life Family Impact Module, Patient Health Questionnaire-4, and post-traumatic stress disorder (PTSD) Checklist for DSM-5. The group-based trajectory model was used to identify recovery patterns. We included 128 parents of children aged 1 month to 18 years, admitted to the PICU for ≥48 h. Three post-discharge composite health trajectory groups were classified: 54 mild (42%), 68 moderate (53%), and 6 severe (4%). Parents in the mild and moderate groups returned to baseline health within the first 3 months, but those in the severe group exhibited worse outcomes at 6-months. The mean (SD) PICU stay durations for mild, moderate, and severe groups were 9 (16), 7 (10), and 38 (61) days; days of mechanical ventilation were 4 (5), 4 (7), and 18 (25) days; and readmission rates were 12 (22%), 23 (34%), and 4 (66%), respectively. Identifying these trajectories enables novel, targeted interventions for at-risk parents, underscoring the significance of integrated PICU follow-up care.

Two months outcomes following delirium in the pediatric intensive care unit.

The lasting consequences of delirium in children are not well characterized. This study aimed to compare the two-month outcomes in pediatric intensive care unit (PICU) survivors according to the presence of delirium. Post-hoc analysis of a single-center prospective study of mechanically ventilated (invasive ventilation or non-invasive ventilation) children followed at the CHU Sainte-Justine PICU follow-up clinic two months after PICU discharge, between October 2018 and August 2022. Delirium was defined as one or more Cornell Assessment of Pediatric Delirium (CAPD) scores ≥ 9. Primary outcome was survivors' quality of life and secondary outcomes were sleep and posttraumatic stress and anxiety and depression in parents. Multivariable linear and logistic regression models assessed the independent associations between delirium and outcomes while adjusting for age, sex, comorbidity, diagnosis, severity of illness, PICU length of stay, and invasive mechanical ventilation. Of the 179 children included over a 47 month-period, 117 (65.4%) had delirium. Children with delirium were more commonly intubated (91.5% vs. 30.7%, p < 0.001) and had higher PELOD-2 scores (10 vs. 4, p < 0.001). On multivariable analysis, delirium was associated with a decreased quality of life at 2.3 months post discharge (p = 0.03). The severity of the delirium episode (higher scores of CAPD) was associated with a higher likelihood of sleep disturbances (OR 1.13, p = 0.01) and parental anxiety (OR 1.16, p = 0.01), in addition to lower quality of life (p = 0.03).Conclusions: Two months following their PICU stay, children with delirium had a lower quality of life, suggesting a lasting effect of delirium on children and their families.

Mortality and associated factors among children admitted to an intensive care unit in muhimbili national hospital, from the time of admission to three months after discharge: a prospective cohort study

BackgroundMortality of children admitted to Intensive Care Units (ICU) is higher in low-to-middle-income countries (LMICs) as compared to high-income countries (HICs). There is paucity of information on outcomes following discharge from ICU, especially from sub-Saharan Africa region. This study was conducted to determine mortality and its associated factors among children admitted to Pediatric ICU (PICU) at Muhimbili National Hospital, from admission to three months after discharge.MethodologyThis was a hospital-based prospective cohort study conducted between July 2021 and May 2022, among children admitted to PICU who were followed up for 3-month after discharge. Structured questionnaires were used to collect data from their medical charts. Telephone interviews were made after discharge. Medical records and verbal autopsy were used to determine the cause of death after discharge. Cox regression analysis was performed to assess the association between variables. A p-value of < 0.05 was considered statistically significant. Survival after PICU discharge was estimated by Kaplan - Meier curve.ResultsOf 323 children recruited, 177(54.8%) were male, with a median age of 17 months (1-168). The leading cause of PICU admission was severe sepsis 90/323(27.9%). A total of 161/323 children died, yielding an overall mortality of 49.8%. Of 173 children discharged from PICU, 33(19.1%) died. The leading cause of death among children who died in the general ward or as readmission into PICU was sepsis 4/17(23.5%). Respiratory diseases 4/16(25.0%) were the commonest cause of death among those who died after hospital discharge. Independent predictors of overall mortality included single organ dysfunction with hazard ratio(HR):5.97, 95% confidence interval (CI)(3.05–12.26)] and multiple organ dysfunction [HR:2.77,95%CI(1.03–2.21)]. Chronic illness[HR:8.13,95%CI(2.45–27.02)], thrombocytosis [HR:3.39,95%CI(1.32–8.73)], single[HR:3.57,95%CI(1.42–9.03)] and multiple organ dysfunction[HR:3.11,95%CI(1.01–9.61)] independently predicted post-PICU discharge mortality.ConclusionOverall mortality and post- PICU discharge mortality were high and more likely to affect children with organ dysfunction, chronic illness, and thrombocytosis. The leading causes of mortality post- PICU discharge were sepsis and respiratory diseases. There is a need for a focused follow up plan of children post- PICU discharge, further research on the long term survival and strategies to improve it.

Characteristics and outcomes of critically ill children with moderate-to-severe traumatic brain injury

ObjectiveTo characterize outcomes of paediatric moderate-to-severe traumatic brain injury (TBI), defined by a Glasgow Coma Scale (GCS) ≤ 12.DesignRetrospective, single-centre cohort study (July 2010 and June 2020).SettingMedical-surgical tertiary paediatric intensive care unit (PICU) in a level 1 university medical trauma centre.PatientsOne-hundred and thirty subjects < 18 years (moderate N = 56, severe N = 74).Measurements and main resultsSubjects were stratified according to favourable (Paediatric Cerebral Performance Category [PCPC] Scale ≤ 3) and poor (PCPC ≥ 4) neurological outcome determined at PICU discharge. One-hundred and six patients (81.5%) had PCPC ≤ 3; of those, N = 55 (52%) had moderate TBI and N = 51 (48%) severe TBI. Twelve patients (9.2%) died, of whom eight (66.7%) within 24 h of PICU admission. Intracranial pressure (ICP) monitoring was performed in N = 12 (50%) patients with PCPC ≥ 4 and in N = 15 (14.2%) patients with PCPC ≤ 3. No clinically relevant differences in serum sodium, glucose, temperature, or blood pressure management during the first 72 h of PICU admission were observed between patients with and without favourable outcome. Mortality was highest among patients with severe TBI (N = 11, 14.9%). Among survivors with PCPC ≥ 4, N = 11 (91.7%) were discharged to a rehabilitation facility compared to N = 22 (20.8%) with PCPC ≤ 3.ConclusionSevere paediatric TBI (pTBI) remains an important cause of serious morbidity and mortality. Patients with moderate pTBI had a favourable outcome at PICU discharge, although the outcome measurement used may not be granular enough to discriminate. Follow-up after discharge is essential to optimize outcome on physical, cognitive, behavioural, and social functioning.

Design and rationale of the Post-Intensive Care Syndrome – paediatrics (PICS-p) Longitudinal Cohort Study

IntroductionAs paediatric intensive care unit (PICU) mortality declines, there is growing recognition of the morbidity experienced by children surviving critical illness and their families. A comprehensive understanding of the adverse...

Ethnic differences in parental experiences during the first six months after PICU discharge in Singapore: a qualitative study.

Literature on parental experiences after childhood critical illness has limited representation from diverse ethnic backgrounds. Parents from global ethnic majority groups have reported worst psychological outcomes and required more social support after childhood critical illness. To explore the experiences of Chinese, Malay, and Indian parents in the first six months after Pediatric Intensive Care Unit (PICU) discharge of their child in Singapore. Sequential semi-structured qualitative interviews were conducted to collect data from a convenience sample of 28 parents at one month (n = 28) and at six months (n = 22) after their child's discharge from a multidisciplinary PICU. Framework Analysis was adopted as the qualitative analysis strategy. The PICS-p framework was applied a priori in the Framework Analysis. Three interdependent domains and seven themes framed the 28 accounts in which ethnically diverse parents reported psychological stressors (PICS-p: emotional health), support received (PICS-p: social health) and practical challenges (transitional health) in the first six months after childhood critical illness. In the emotional health domain, parents were affected by different stressors and had different priorities over their child's survivorship. Only Indian parents reported experiences of stress symptoms, at six months post discharge. Malay parents sought solace from their religion more than Chinese and Indian parents. In the social health domain, parents reported various sources and degree of support received. Familial supports were strong across all groups, while community support was more prominent in Malay as compared to Chinese and Indian parents. A third domain, transitional health, was introduced to capture the difficulties parents faced during the transition from PICU survival to home. Parents from non-Chinese families were more likely to report financial challenges and more involvement of spouses after discharge. Complementary medicine or commercial health products were utilized by Chinese and Malay families. These findings reveal preferred strategies that parents from a global ethnic employ to address the emotional, social and transitional health impacts of their child's critical illness. Future care delivery may consider tailored care plans, communication strategies, and emotional support in PICUs that address the unique ethnic needs of parents during the critical six-months post their child's illness.

Navigating Stress in the Pediatric Intensive Care Unit Among Parents of Children with Severe Neurological Impairment.

Children with severe neurological impairment (SNI) make up nearly 50% of pediatric intensive care unit (PICU) admissions, yet little is known about their family caregiver experiences. To examine how parents and family caregivers of children with SNI navigate stress during PICU admissions. This qualitative single-center study used content and thematic networks analysis to evaluate data from 1:1 semistructured interviews conducted around the time of PICU discharge with parents and family caregivers of children with SNI to examine ways they navigate stress. Proportions of participants reporting each theme and subtheme were calculated. Fifteen parents/family caregivers of 15 children with SNI participated. Children were a median of 8 years old (range 1-21 years) and the majority had congenital/chromosomal conditions leading to their neurologic condition (80%, n = 12). 20% of participants were fathers (n = 3) and 45% (n = 7) reported identifying as having a minority racial background. Themes included 1) self-activation, and 2) letting go and the majority (80%, n = 12) of parents reported using both self-activation and letting go strategies. Within each of these themes, 5 subthemes illustrated ways parents navigate stress. The most reported subthemes were advocating and showing up (53%, n = 8) and being supported by compassionate clinicians (67%, n = 10). Themes/subthemes were used to create recommended language to guide clinicians in supporting parents. Parents and family caregivers of children with SNI employ various ways to navigate stress in the PICU. Themes from this study can be used to develop interventions that meet the psychosocial needs of parents and family caregivers of children with SNI during highly stressful times.

Implementation and effectiveness of a delirium care protocol in Thai critically ill children.

Delirium in critically ill children can result in long-term morbidity. Our main objectives were to evaluate the effectiveness of a new protocol on the reduction, prevalence, and duration of delirium and to identify associated risk factors. The effectiveness of the protocol was evaluated by a chart review in all critically ill children aged 1 month to 15 years during the study period. A Cornell Assessment of Pediatric Delirium score ≥9 was considered positive for delirium. Data on delirium prevalence and duration from the pre-implementation and post-implementation phases were compared. Univariate and multivariate analyses were used to identify the risk factors of delirium. A total of 120 children was analyzed (58 children in the pre-implementation group and 62 children in the post-implementation group). Fifty children (41.7%) screened positive for delirium. Age less than 2 years, delayed development, use of mechanical ventilation, and pediatric intensive care unit (PICU) stay >7 days were significantly associated with delirium. The proportion of children screened positive was not significantly different after the implementation (before, 39.7% vs. after, 43.5%; P=0.713). Subgroup analyses revealed a significant reduction in the duration of delirium in children with admission diagnosis of cardiovascular problems and after cardiothoracic surgery. The newly implemented protocol was able to reduce the duration of delirium in children with admission diagnosis of cardiovascular problems and after cardiothoracic surgery. More studies should be conducted to reduce delirium to prevent long-term morbidity after PICU discharge.

Neurofilament light as a predictor of long- and short-term outcomes in critically ill children

PurposePlasma neurofilament light (NFL) is a marker of neuronal injury, associated with poor neurological outcomes in adults and neonates in a wide range of diseases. We sought to describe the associations between NFL at admission (NFLadm) and outcomes in a heterogenous cohort of critically ill children needing unplanned admission to the pediatric intensive care unit (PICU).Materials and methodsWe analysed prospectively collected biobank samples from critically-ill children with unplanned admissions to PICU. Samples were selected for survivors who had a 12-month follow-up with parent-completed Pediatric Quality of Life Inventory (PedsQL) scores as the primary outcome of interest.ResultsData from 52 children were analysed. The median NFL was 17.0 pg/ml (IQR 5.8–28.1). There were no significant associations between NFLadm levels and PedsQL (NFLadm-adjusted odds ratio 0.99, 95% CI 0.97, 1.02) at 12 months. NFL showed associations with outcomes at PICU discharge, such as change in functional status and need for organ support but interpretation is limited by sample size.ConclusionsAdmission NFL values were not associated with 12-month quality of life outcomes in a heterogenous cohort of children admitted to PICU.

Exposure to Sedation and Analgesia Medications: Short-term Cognitive Outcomes in Pediatric Critical Care Survivors With Acquired Brain Injury.

Background/Objective: Pediatric intensive care unit (PICU) survivors risk significant cognitive morbidity, particularly those with acquired brain injury (ABI) diagnoses. Studies show sedative and analgesic medication may potentiate neurologic injury, but few studies evaluate impact on survivor outcomes. This study aimed to evaluate whether exposures to analgesic and sedative medications are associated with worse neurocognitive outcome. Methods: A retrospective cohort study was conducted of 91 patients aged 8 to 18 years, undergoing clinical neurocognitive evaluation approximately 1 to 3 months after PICU discharge. Electronic health data was queried for sedative and analgesic medication exposures, including opioids, benzodiazepines, propofol, ketamine, and dexmedetomidine. Doses were converted to class equivalents, evaluated by any exposure and cumulative dose exposure per patient weight. Cognitive outcome was derived from 8 objective cognitive assessments with an emphasis on executive function skills using Principal Components Analysis. Then, linear regression was used to control for baseline cognitive function estimates to calculate a standardized residualized neurocognitive index (rNCI) z-score. Multivariable linear regression evaluated the association between rNCI and medication exposure controlling for covariates. Significance was defined as P < .05. Results: Most (n = 80; 88%) patients received 1 or more study medications. Any exposure and higher cumulative doses of benzodiazepine and ketamine were significantly associated with worse rNCI in bivariate analyses. When controlling for Medicaid, preadmission comorbid conditions, length of stay, delirium, and receipt of other medication classes, receipt of benzodiazepine was associated with significantly worse rNCI (β-coefficient = -0.48, 95% confidence interval = -0.88, -0.08). Conclusions: Exposure to benzodiazepines was independently associated with worse acute phase cognitive outcome using objective assessments focused on executive function skills when controlling for demographic and illness characteristics. Clinician decisions regarding medication regimens in the PICU may serve as a modifiable factor to improve outcomes. Additional inquiry into associations with long-term cognitive outcome and optimal medication regimens is needed.

THU155 Aberrant DNA Methylation Within Genes Of The HPA-axis Two Years After Paediatric Critical Illness, Role Of Glucocorticoid Treatment And Association With Impaired Physical And Neurocognitive Development.

Abstract Disclosure: G. Coppens: None. I. Vanhorebeek: None. F. Guïza: None. I. Derese: None. P.J. Wouters: None. J.F. Koen: None. S.C. Verbruggen: None. G. Van den Berghe: None. Critically ill children requiring intensive care suffer from impaired physical, neurocognitive and behavioural development two years later. Other severe early-life adverse events, such as abuse or neglect occurring during sensitive neurodevelopmental windows, have been associated with similar developmental problems. Earlier work has demonstrated the risk of impaired development of brain regions crucial for cognition and behaviour through increased glucocorticoid-signalling that, when prolonged or excessive, can induce aberrant DNA methylation within the hypothalamus-pituitary-adrenal (HPA) axis. We hypothesised that paediatric critical illness induces long-term DNA methylation changes within the HPA-axis, possibly aggravated by treatment with glucocorticoids in the paediatric intensive care unit (PICU), which may contribute to the long-term physical, neurocognitive and behavioural impairments. We assessed buccal mucosal DNA methylation (Infinium-Human Methylation-EPIC-BeadChip) of former PICU patients two years after PICU discharge (N=608 No-glucocorticoid-treatment; N=210 glucocorticoid-treatment) and matched healthy children (N=392) among key genes of the different layers of the HPA-axis. CpG-sites differentially methylated between groups were identified with use of multivariable linear regression. Differentially methylated DNA-regions were detected via clustering of differentially methylated CpG-sites using kernel estimates. These analyses were adjusted for technical variation and baseline risk factors and corrected for multiple testing (FDR&amp;lt;0.05). Additionally, we investigated to what extent glucocorticoid treatment during PICU stay had played a direct role in bringing about any DNA methylation changes. Finally, we assessed whether an association with the long-term physical, neurocognitive and behavioural impairment was present, with use of multivariable linear models. Former PICU patients showed aberrant DNA methylation at 10 CpG-sites (located within NR3C1, FKBP5, TSC22D3, TNF and, HSD11B1) and one DNA-region (located within TNF). Additionally, we identified that the differential methylation of 2 CpG-sites within FKBP5 was at least partly attributable to the glucocorticoid treatment that was given during PICU stay. The aberrant DNA methylation in former PICU patients associated with impaired development. This was most pronounced for the hypomethylation within the promotor/5’UTR region of FKBP5, which associated with worse growth, intelligence, visual-motor integration, alertness and memory. Two years after critical illness in children, aberrant DNA methylation within different genes of the HPA axis was detected, some of which may partly be explained by the glucocorticoid treatment given during PICU admission. These changes associated with long-term physical and neurocognitive impairments of former PICU patients. Presentation: Thursday, June 15, 2023

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

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

Analyzing Mortality Trends in the UK Pediatric Critical Care Long-Stay Patient Cohort

AbstractLong-stay patients in pediatric intensive care unit (PICU) are at risk of higher mortality. The long-stay PICU population is growing larger. Identification of indicators of adverse outcomes in this cohort may provide opportunities for timely counseling and support. We aim to analyze the factors associated with higher mortality in the long-stay PICU patient cohort. Retrospective single-center study of long-stay PICU admissions defined as a PICU length of stay of at least 28 days during a 3-year study period (April 1, 2017–March 31, 2020). Outcomes analyzed included in-PICU mortality and mortality within 12 months of PICU discharge. Variables analyzed for association with outcomes included primary diagnostic category, number and nature of additional comorbidities, long-term ventilation (LTV) pathway, etc. During a 3-year period, there were 2,848 unique individual patient admissions to the PICU; 165 children had 172 long-stay admissions. The overall in-PICU mortality of long-stay patient was 30.2% compared with 6.4% (p &lt; 0.0001) for whole PICU population; 42% of the long-stay patients had died by 12 months postdischarge. Certain primary diagnostic groups, for example, hematology/oncology, had a statistically significant increased likelihood of death (odds ratio [OR] 8.6 [p = 0.004, confidence interval, CI, 2.0–39.5]). Children on an LTV pathway had relatively lower odds of death (OR 0.1 [p = 0.003, CI 0.01–0.34]). We described factors associated with higher and lower mortality rates in a group of long-stay PICU patients. Understanding the impact of specific combinations of factors as shown in this analysis on outcomes may be important for clinicians to help counsel families.

Prognostic Markers in Pediatric Acute Liver Failure

Introduction: Acute liver failure (ALF), although rare in children, is a complex progressive pathology, with multisystem involvement and high mortality. Isolated variables or those included in prognostic scores have been studied, to optimize organ allocation. However, its validation is challenging. This study aimed to assess the accuracy of several biomarkers and scores as predictors of prognosis in pediatric ALF (PALF). Methods: An observational study with retrospective data collection, including all cases of ALF, was defined according to the criteria of the Pediatric Acute Liver Failure Study Group, admitted to a pediatric intensive care unit (PICU) for 28 years. Two groups were defined: spontaneous recovery (SR) and non-SR (NSR) – submitted to liver transplantation (LT) or death at PICU discharge. Results: Fifty-nine patients were included, with a median age of 24 months, and 54% were female. The most frequent etiologies were metabolic (25.4%) and infectious (18.6%); 32.2% were undetermined. SR occurred in 21 patients (35.6%). In NSR group (N = 38, 64.4%), 25 required LT (42.4%) and 19 died (32.2%), 6 (15.7%) of whom after LT. The accuracy to predict NSR was acceptable for lactate at admission (AUC 0.72; 95% CI: 0.57–0.86; p = 0.006), ammonia peak (AUC 0.72; 95% CI: 0.58–0.86; p = 0.006), and INR peak (AUC 0.70; 95% CI: 0.56–0.85; p = 0.01). The cut-off value for lactate at admission was 1.95 mmol/L (sensitivity 78.4% and specificity 61.9%), ammonia peak was 64 μmol/L (sensitivity 100% and specificity 38.1%), and INR peak was 4.8 (sensitivity 61.1% and specificity 76.2%). Lactate on admission was shown to be an independent predictor of NSR on logistic regression model. Two prognostic scores had acceptable discrimination for NSR, LIU (AUC 0.73; 95% CI: 0.59–0.87; p = 0.004) and PRISM (AUC 0.71; 95% CI: 0.56–0.86; p = 0.03). In our study, the PALF delta score (PALF-ds) had lower discrimination capacity (AUC 0.63; 95% CI: 0.47–0.78; p = 0.11). Conclusions: The lactate at admission, an easily obtained parameter, had a similar capacity than the more complex scores, LIU and PRISM, to predict NSR. The prognostic value in our population of the promising dynamic score, PALF-ds, was lower than expected.

Predictors of neurocognitive and psychological disorders in children after intensive care admission: A prospective cohort study.

Children admitted in the pediatric intensive care unit (PICU) often deal with long-term morbidities affecting physical, cognitive, emotional, social, and psychiatric symptoms. We aimed to identify the internal and external factors which predict the occurrence of neurocognitive and psychological disorders in survivors at 3 months after PICU discharge. We identified 53 critically ill children, ages 4-18 years old, admitted in PICU for more than 24 h, and survived. We evaluated neurocognitive disorder with Pediatric Cerebral Perfomance Category (PCPC) and psychological disorders with Strengths and Difficulties Questionnaire (SDQ) at the time of PICU discharge and repeated in 3 months afterward. We evaluated the internal and external risk factors related to neurocognitive and psychological disorders in PICU survivors. The internal risk factors were age, gender, family composition, and socioeconomic status. The external risk factors were: surgical intervention, neurological disease, predicted death rate by pediatric index mortality (PIM)-2 score, PICU length of stay (LOS), days of mechanical ventilation, and the number of therapeutic interventions. There were significant improvement in neurocognitive disorders (p < 0.001), peer problems, (p = 0.01), and prosocial behaviors (p = 0.00) in children at 3 months after the PICU discharge. Age of 4-5 years has a significant effect on neurocognitive disorders (p = 0.04), while male gender (p = 0.02), low-social economy, non-intact family composition (p = 0.01), neurological disease (p = 0.04), surgical intervention (p = 0.01), and TISS score (p = 0.00) have a significant effect on psychological disorders in children at 3 months after the PICU discharge. Neurocognitive disorders, peer problems, and prosocial behaviors improved in a few patients 3 months after PICU discharge. Age of 4-5 years was a risk factor of the persisted neurocognitive disorder, whereas male gender, low-social economy, non-intact family composition, neurological disease, surgical intervention, and TISS score were risk factors of persisted psychological disorder at 3 months after PICU.