Inflammation and psychopathology in children following PICU admission: an exploratory study.

BACKGROUND: Survivors of critical illness in childhood commonly display subsequent psychiatric symptoms including emotional and behavioural difficulties, and manifestations of post-traumatic stress disorder (PTSD). Anomalies in inflammatory profiles are an established finding in these childhood psychiatric conditions. OBJECTIVE: This exploratory study aimed to investigate whether abnormal peripheral blood inflammatory markers measured during paediatric intensive care unit (PICU) admission were associated with psychiatric symptoms after discharge. METHODS: We performed a prospective observational cohort study on 71 children with septic illness, meningoencephalitis and other critical disorders admitted to two PICUs between 2007 and 2010. 3-6 months following discharge, subjects were assessed for global psychiatric risk (ie, presence of emotional and behavioural difficulties on the parental Strengths and Difficulties Questionnaire (SDQ)), and for PTSD risk using the child-rated Impact of Events Scale (IES-8). Inflammatory and related biological markers were transcribed from PICU admission notes (white cell count, lymphocytes, neutrophils, C reactive protein (CRP), platelets, fibrinogen and lactate). FINDINGS: Global psychiatric risk at follow-up was associated with abnormal lymphocyte count during admission (χ2=6.757, p=0.014, n=48). In children with sepsis, partial correlation analyses controlling for age and gender highlighted associations between (i) SDQ scores and low lymphocyte count (r=-0.712; p=0.009, n=14), and (ii) IES-8 score and high CRP levels (r=0.823; p=0.006, n=11). These associations remained after correction for multiple comparisons. CONCLUSION: These results support the hypothesis that acute inflammation may play a role in determining the development of psychopathology following PICU admission. CLINICAL IMPLICATIONS: If the findings are replicated, they may help to better highlight which children are at risk of post-PICU psychopathology and appropriately target follow-up.

Post-traumatic stress after PICU and corticosteroid use.

AIM: To examine the association between corticosteroid use in paediatric intensive care units (PICU) and subsequent symptoms of post-traumatic stress disorder (PTSD). METHODS: The subjects were children aged 8-16 years admitted to PICU with sepsis, meningoencephalitis (ME) and other disorders. Illness information was extracted from case notes; 3-6 months post discharge children completed a PTSD symptom questionnaire (eight-item Impact of Events Scale (IES-8)) assessing intrusion and avoidance symptoms. Saliva samples were also collected for cortisol profile analysis. RESULTS: 53 children completed the IES-8 questionnaires. 33 provided saliva samples. 19 (36%) received corticosteroids. In children with sepsis (n=15), corticosteroid use was associated with significantly lower PTSD intrusion symptom scores. There was a trend towards an association between corticosteroid use and lower evening cortisol levels. There was a comparable but weaker trend in children with ME. DISCUSSION: Corticosteroid use may be associated with fewer PTSD symptoms and lower evening cortisol levels following PICU admission in children with sepsis.

Stress hormones and posttraumatic stress symptoms following paediatric critical illness: an exploratory study.

In this exploratory case-control study, we investigated basal cortisol regulation in 5-16-year-old children, 3-6 months following PICU (paediatric intensive care) admission. This was nested within a study of child psychological and cognitive function; 47 children were assessed alongside 56 healthy controls. Saliva samples were collected three times per day (immediately after waking, waking +30 min, and waking +12 h) over two consecutive weekdays. In addition, data on posttraumatic stress symptoms were ascertained from 33 PICU admitted children using the Impact of Events Scale-8 (IES-8). Primary analysis revealed no significant differences in basal cortisol concentrations between PICU discharged children and healthy controls (p > 0.05). Secondary analysis in the PICU group identified a significant positive association between posttraumatic stress symptoms and evening (waking +12 h) cortisol concentrations (p = 0.004). However, when subject to multivariate analysis, evening cortisol was a modest independent predictor of IES-8 scores, relative to the presence of septic illness and poor pre-morbid health. We conclude that paediatric critical illness does not appear to result in marked perturbations to basal cortisol at 3-6 month following discharge. There was evidence of a link between evening cortisol and symptoms of PTSD, but this was not a robust effect and requires further elucidation.

A supported psychoeducational intervention to improve family mental health following discharge from paediatric intensive care: feasibility and pilot randomised controlled trial.

OBJECTIVE: To assess feasibility and pilot a supported psychoeducational tool to improve parent and child mental health following discharge from a paediatric intensive care unit (PICU), in preparation for a large randomised controlled trial (RCT). DESIGN: Feasibility assessment and single-centre, parallel group, pilot RCT. A concealed computer generated list was used to randomise participants, with an allocation of 2:1 in favour of the intervention. SETTING: A PICU in an acute care hospital in London, UK. PARTICIPANTS: 31 parents of children aged 4-16 years-old admitted to PICU. INTERVENTION: Parents received a psychoeducational tool supported by a telephone call. The psychoeducational tool outlined the possible psychological reactions in children and parents alongside management advice. The telephone call addressed each family's postdischarge experience, reinforced the psychoeducational material and encouraged parents to put into practice the advice given. MAIN OUTCOME MEASURES: The primary outcome was the number of feasibility criteria successfully met (linked to the intervention and the study design). Secondary outcomes were questionnaire data collected at 3-6-month follow-up assessing mental health in parents and children. RESULTS: 31 parents were randomised (intervention n=22; treatment as usual, TAU n=9). 23 parents were included in the analysis of secondary outcomes (intervention n=17; TAU n=6). 3 (of 6) intervention and 1 (of 6) study design feasibility criteria were fully met. All unmet criteria could be addressed with minor or significant modifications to the protocol. At follow-up there was a tendency for parents who received the intervention to report lower post-traumatic stress symptoms in themselves and fewer emotional and behavioural difficulties in their children than TAU parents. This needs to be explored in a fully powered trial. CONCLUSIONS: This feasibility and pilot RCT provided valuable information on the intervention and trial design for a full RCT. TRIALS REGISTRATION NUMBER: NCT01737021; Results.

Persistence of Neuropsychological Deficits Following Pediatric Critical Illness.

OBJECTIVE: To study 12-month persistence of neuropsychological deficits in PICU survivors. DESIGN: Prospective follow-up study. SETTING: Two PICUs. PARTICIPANTS: Children 5-16 years old with neuropsychological deficits 3-6 months following PICU care for meningoencephalitis, sepsis, and other critical illnesses (excluding other primary neurological disorders). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Neuropsychological function was assessed using the Cambridge Neuropsychological Test Automated Battery, the Children's Memory Scale, and the Wechsler Abbreviated Scale of Intelligence or Wide Range Intelligence Test. Forty-seven of 88 PICU admitted children (53%) were identified as neuropsychologically impaired 3-6 months after discharge; of these, 23 provided 12-month follow-up data. In spite of significant improvements in measures of memory, there was little change in intelligence quotient and visual attention over the study period, and children's educational progress remained below expectation. CONCLUSIONS: We found persistently reduced neuropsychological function following PICU admission in the critical illnesses under study.

Mental and physical well-being following admission to pediatric intensive care.

OBJECTIVE: To assess mental and physical well-being in school-aged children following admission to pediatric intensive care and to examine risk factors for worse outcome. DESIGN: A prospective cohort study. SETTING: Two PICUs. SUBJECTS: A consecutive sample of 88 patients 5-16 years old (median age, 10.00 yr; interquartile range, 6.00-13.00 yr) admitted to PICU from 2007 to 2010 with septic illness, meningoencephalitis, or other critical illnesses were assessed a median of 5 months following discharge and outcomes compared with 100 healthy controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Parents completed questionnaires documenting child mental and physical well-being, including the Strengths and Difficulties Questionnaires, Chalder Fatigue Scale, and Child Sleep Habits Questionnaire. Children over 8 years completed the Impact of Event Scale -8. The children admitted to PICU scored worse on all measures in comparison with the healthy controls, with 20% scoring at risk for psychiatric disorder, 34% with high levels of post-traumatic stress symptoms, 38% at risk for fatigue disorder, and 80% scoring at risk for sleep disturbance. In the PICU group, multivariable regression analyses identified septic illness as an independent predictor of post-traumatic stress symptoms and family status, past child health problems, and PICU length of stay as predictors of reduced general mental well-being. CONCLUSIONS: Our findings indicate that a significant minority of school-aged children admitted to PICU are at risk for reduced mental and physical well-being in the short term. Symptoms of poor mental well-being were linked to both vulnerability factors and critical illness factors.

Neuropsychologic function three to six months following admission to the PICU with meningoencephalitis, sepsis, and other disorders: a prospective study of school-aged children.

OBJECTIVE: To assess short-term neuropsychological function and academic performance in school children following admission to intensive care and to explore the role of critical neurologic and systemic infection. DESIGN: A prospective observational case-control study. SETTING: Two PICUs. SUBJECTS: A consecutive sample of 88 children aged 5-16 years (median age=10.00, interquartile range=6.00-13.00) who were admitted to intensive care between 2007 and 2010 with meningoencephalitis, septic illness, or other critical illnesses. They were assessed 3 to 6 months following discharge, and their performance was compared with that of 100 healthy controls. Patients were without prior neurologic or neurodevelopmental disorder. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data encompassing demographic and critical illness details were obtained, and children were assessed using tests of intellectual function, memory, and attention. Questionnaires addressing academic performance were returned by teachers. After adjusting for covariates, the children admitted to PICUs significantly underperformed on neuropsychological measures in comparison to healthy controls (p<0.02). Teachers deemed more children admitted to PICUs than controls as performing educationally worse and having problems with school work (ps=0.001), as well as performing below average on aspects of executive function and attention (ps<0.04). Analysis of the effect of illness type on outcome revealed that aspects of neuropsychological function, such as memory function, and teacher-rated academic performance were most reduced in children with meningoencephalitis and septic illness. In the PICU group, multivariable linear regression revealed that worse performance on a composite score of neuropsychologic impairment was more prevalent when children were younger, from a lower social class, and had experienced seizures during their admission (ps<0.02). CONCLUSIONS: Admission to intensive care is followed by deficits in neuropsychologic performance and educational difficulties, with more severe difficulties noted following meningoencephalitis and septic illness. These results highlight the importance of future studies on cognition and educational outcome incorporating type of illness as a moderating factor.

Long-lasting semantic context effects in the spoken production of object names.

A number of recent studies have found that objects are named more slowly in the context of same-category items than in the context of items from various semantic categories. Several experiments reported here indicated that this semantic effect is relatively persistent because it was essentially unaffected by the presence of interspersed filler items. The authors suggest that the effect is specific to the retrieval of lexical-semantic codes and characterize mechanisms that could support the effect at this processing level, such as incremental learning in the links between conceptual and lexical codes and the temporary increase of lexical resting levels. The results underscore the necessity of incorporating mechanisms of long-term adaptation into current models of spoken production.