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Use of magnetic resonance imaging (MRI) as a tool to aid in neuroprognostication after cardiac arrest (CA) has been described, yet details of specific indications, timing, and sequences are unknown. We aim to define the current practices in use of brain MRI in prognostication after pediatric CA.A survey was distributed to pediatric institutions participating in three international studies. Survey questions related to center demographics, clinical practice patterns of MRI after CA, neuroimaging resources, and details regarding MRI decision support.Response rate was 31% (44 of 143). Thirty-four percent (15 of 44) of centers have a clinical pathway informing the use of MRI after CA. Fifty percent (22 of 44) of respondents reported that an MRI is obtained in nearly all patients with CA, and 32% (14 of 44) obtain an MRI in those who do not return to baseline neurological status. Poor neurological examination was reported as the most common factor (91% [40 of 44]) determining the timing of the MRI. Conventional sequences (T1, T2, fluid-attenuated inversion recovery, and diffusion-weighted imaging/apparent diffusion coefficient) are routinely used at greater than 97% of centers. Use of advanced imaging techniques (magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI) were reported by less than half of centers.Conventional brain MRI is a common practice for prognostication after CA. Advanced imaging techniques are used infrequently. The lack of standardized clinical pathways and variability in reported practices support a need for higher-quality evidence regarding the indications, timing, and acquisition protocols of clinical MRI studies.

Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric population are less studied and there is no standard method to identify those at risk for developing infections. Our goal was to better understand immune dysfunction and identify soluble protein markers following pediatric thermal injury. Further we wanted to determine which early inflammatory, soluble, or immune function markers are most predictive of the development of nosocomial infections (NI) after burn injury. We performed a prospective observational study at a single American Burn Association-verified Pediatric Burn Center. A total of 94 pediatric burn subjects were enrolled and twenty-three of those subjects developed a NI with a median time to diagnosis of 8 days. Whole blood samples, collected within the first 72 hours after injury, were used to compare various markers of inflammation, immune function, and soluble proteins between those who recovered without developing an infection and those who developed a NI after burn injury. Within the first three days of burn injury, innate and adaptive immune function markers (ex vivo lipopolysaccharide-induced tumor necrosis factor alpha production capacity, and ex vivo phytohemagglutinin-induced interleukin-10 production capacity, respectively) were decreased for those subjects who developed a subsequent NI. Further analysis of soluble protein targets associated with these pathways displayed significant increases in soluble CD27, BTLA, and TIM-3 for those who developed a NI. Our findings indicate that suppression of both the innate and adaptive immune function occurs concurrently within the first 72 hours following pediatric thermal injury. At the same time, subjects who developed NI have increased soluble protein biomarkers. Soluble CD27, BTLA, and TIM-3 were highly predictive of the development of subsequent infectious complications. This study identifies early soluble protein makers that are predictive of infection in pediatric burn subjects. These findings should inform future immunomodulatory therapeutic studies.

Critical injury-induced immune suppression has been associated with adverse outcomes. This acquired form of immunosuppression is poorly understood in pediatric burn patients, who have infectious complication rates as high as 71%. Our primary objectives were to determine if thermal injury results in early innate immune dysfunction and is associated with increased risk for nosocomial infections (NI). We performed a prospective, longitudinal immune function observational study at a single pediatric burn center. Whole blood samples from burn patients within the first week of injury were used to assess innate immune function. Nosocomial infections were defined using CDC criteria. Immune parameters were compared between patients who went on to develop NI and those that did not. We enrolled a total of 34 patients with 12 developing a NI. Within the first 3 days of injury, children whom developed NI had significantly lower whole blood ex vivo LPS-induced TNFα production capacity (434 pg/mL vs 960 pg/mL, P = .0015), CD14+ monocyte counts (273 cells/µL vs 508 cells/µL, P = .01), and % HLA-DR expression on CD14+ monocytes (54% vs 92%, P = .02) compared with those that did not develop infection. Plasma cytokine levels did not have a significant difference between the NI and no NI groups. Early innate immune suppression can occur following pediatric thermal injury and appears to be a risk factor for the development of nosocomial infections. Plasma cytokines alone may not be a reliable predictor of the development of NI.

OBJECTIVES Nosocomial infection is a common source of morbidity in critically injured children including those with traumatic brain injury. Risk factors for nosocomial infection in this population, however, are poorly understood. We hypothesized that critically ill pediatric trauma patients with traumatic brain injury would demonstrate higher rates of nosocomial infection than those without traumatic brain injury. DESIGN Retrospective case-control study. SETTING PICU, single institution. PATIENTS Patients under 18 years old who were admitted to the PICU for at least 48 hours following a traumatic injury were included. Patients were admitted between September 2008 and December 2015. Patients with the following injury types were excluded: thermal injury, drowning, hanging/strangulation, acute hypoxic ischemic encephalopathy, or nonaccidental trauma. Data collected included demographics, injury information, hospital and PICU length of stay, vital signs, laboratory data, insertion and removal dates for invasive devices, surgeries performed, transfusions of blood products, and microbiology culture results. Initial Pediatric Risk of Mortality III and Pediatric Logistic Organ Dysfunction-2 scores were determined. Patients were classified as having: 1) an isolated traumatic brain injury, 2) a traumatic injury without traumatic brain injury, or 3) polytrauma with traumatic brain injury. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Two hundred three patients were included in the analyses, and 27 patients developed a nosocomial infection. Patients with polytrauma with traumatic brain injury demonstrated a significantly higher infection rate (30%) than patients with isolated traumatic brain injury (6%) or traumatic injury without traumatic brain injury (9%) (p < 0.001). This increased rate of nosocomial infection was noted on univariate analysis, on multivariable analysis, and after adjusting for other risk factors. CONCLUSIONS In this single-center, retrospective analysis of critically ill pediatric trauma patients, nosocomial infections were more frequently observed in patients admitted following polytrauma with traumatic brain injury than in patients with isolated traumatic brain injury or trauma without traumatic brain injury.

Objective To test the hypothesis that early RBC transfusion is associated with duration of organ dysfunction in critically ill septic children. Design Secondary analysis of a single-center prospective observational study. Multivariable negative binomial regression was used to determine relationships between RBC transfusion within 48 hours of sepsis onset and number of days in 14 with organ dysfunction, or with multiple organ dysfunction syndrome. Setting A PICU at a quaternary care children's hospital. Patients Children less than 18 years old with severe sepsis/septic shock by consensus criteria were included. Patients with RBC transfusion prior to sepsis onset and those on extracorporeal membrane oxygenation support within 48 hours of sepsis onset were excluded. Interventions None. Measurements and main results Ninety-four patients were included. Median age was 6 years (0-13 yr); 61% were male. Seventy-eight percentage had septic shock, and 41 (44%) were transfused RBC within 48 hours of sepsis onset (early RBC transfusion). On multivariable analyses, early RBC transfusion was independently associated with 44% greater organ dysfunction days (adjusted relative risk, 1.44 [1.04-2.]; p = 0.03), although risk differed by severity of illness (interaction p = 0.004) and by shock severity (interaction p = 0.04 for Vasoactive Inotrope Score and 0.03 for shock index). Relative risks for multiple organ dysfunction syndrome days varied by shock severity (interaction p = 0.008 for Vasoactive Inotrope Score and 0.01 for shock index). Risks associated with early RBC transfusion were highest for the children with the lowest shock severities. Conclusions In agreement with previous studies, early RBC transfusion was independently associated with longer duration of organ dysfunction. Ours is among the first studies to document different transfusion-associated risks based on clinically available measures of shock severity, demonstrating greater transfusion-associated risks in children with less severe shock. Larger multicenter studies to verify these interaction effects are essential to plan much-needed RBC transfusion trials for critically ill septic children.

OBJECTIVES To serially evaluate health-related quality of life during the first year after community-acquired septic shock in children with preexisting severe developmental disabilities and explore factors associated with health-related quality of life changes in these children. DESIGN Secondary analysis of the Life after Pediatric Sepsis Evaluation investigation. SETTING Twelve academic PICU in the United States. PATIENTS Children greater than or equal to 1 month and less than 18 years old identified by their family caregiver (e.g., parent/guardian) as having severe developmental disability prior to septic shock. INTERVENTIONS Family caregivers completed the Stein-Jessop Functional Status II-R Short Form as a measure of their child's health-related quality of life at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Stein-Jessop Functional Status II-R Short Form scores were linearly transformed to a 0-100 scale, with higher scores indicating better health-related quality of life. MEASUREMENTS AND MAIN RESULTS Of 392 Life after Pediatric Sepsis Evaluation participants, 137 were identified by their caregiver as having a severe developmental disability. Sixteen children (11.6%) with severe disability died during the 12 months following septic shock. Among 121 survivors, Stein-Jessop Functional Status II-R Short Form scores declined from preadmission baseline to day 7 (70.7 ± 16.1 vs 55.6 ± 19.2; p < 0.001). Stein-Jessop Functional Status II-R Short Form scores remained below baseline through month 12 (59.1 ± 21.0, p < 0.001 vs baseline). After adjusting for baseline Stein-Jessop Functional Status II-R Short Form, the caregiver being a single parent/guardian was associated with lower month 3 Stein-Jessop Functional Status II-R Short Form scores (p = 0.041). No other baseline child or caregiver characteristic, or critical illness-related factors were significantly associated with month 3 Stein-Jessop Functional Status II-R Short Form scores. CONCLUSIONS Health-related quality of life among children with severe developmental disability remains, on average, below baseline during the first year following community-acquired septic shock. Children with severe disability and septic shock that are in single parent families are at increased risk. Clinical awareness of the potential for decline in health-related quality of life among disabled children is essential to prevent this adverse outcome from being missed.

IntroductionBlood and imaging biomarkers show promise in prognosticating outcomes after paediatric cardiac arrest in pilot studies. We describe the methods and early recruitment challenges and solutions for an ongoing multicentre (n=14) observational trial, Personalising Outcomes following Child Cardiac Arrest to validate clinical, blood and imaging biomarkers individually and together in a clinically relevant panel.Methods and analysisChildren (n=164) between 48 hours and 17 years of age who receive chest compressions irrespective of provider, duration, or event location and are admitted to an intensive care unit are eligible. Blood samples will be taken on days 1–3 for the measurement of brain-focused biomarkers analysed to predict the outcome. Clinically indicated and timed brain MRI and spectroscopy biomarkers will be analysed to predict the outcome. The primary outcome for the trial is survival with favourable (Vineland Adaptive Behavioural Scale score >70) outcome at 1 year. Secondary outcomes include mortality and pre-event and postdischarge measures of emotional, cognitive, physical and family functioning and health-related quality of life. Early enrollment targets were not met due to prolonged regulatory and subcontract processes. Multiple, simultaneous interventions including modification to inclusion criteria, additional sites and site visits were implemented with successful improvement in recruitment. Study procedures including outcomes and biomarker analysis are ongoing.Ethics and disseminationTwelve of 14 sites will use the centralised Institutional Review Board (IRB) at the University of Pittsburgh (PRO14030712). Two sites will use individual IRBs: Children’s Healthcare of Atlanta Institutional Review Board and Children’s Hospital of Wisconsin IRB. Parents and/or guardians are consented and children assented (when possible) by the site Primary investigator (PI) or research coordinator for enrollment. Study findings will be disseminated through scientific conferences, peer-reviewed journal publications, public study website materials and invited lectures.Trial registration numberNCT02769026.

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era.Retrospective observational study.Emergency departments and ICUs at two academic children's hospitals.Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge.None.Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction.Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies were limited. A pattern of persistent, rather than worsening, organ dysfunction preceded most deaths.

Rationale: Late immune suppression is associated with nosocomial infection and mortality in adults and children with sepsis. Relationships between early immune suppression and outcomes in children with sepsis remain unclear. Objectives: Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis or septic shock. Methods: Children younger than 18 years of age meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy control subjects were sampled once. Innate immune function was quantified by whole blood ex vivo LPS-induced TNF-α (tumor necrosis factor-α) production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFN-γ production capacity. Measurements and Main Results: One hundred two children with sepsis and 35 healthy children were enrolled. Compared with healthy children, children with sepsis demonstrated lower LPS-induced TNF-α production (P