Morphological and ultrastructural investigation of the posterior atlanto-occipital membrane: Comparing children with Chiari malformation type I and controls.

INTRODUCTION: The fibrous posterior atlanto-occipital membrane (PAOM) at the craniocervical junction is typically removed during decompression surgery for Chiari malformation type I (CM-I); however, its importance and ultrastructural architecture have not been investigated in children. We hypothesized that there are structural differences in the PAOM of patients with CM-I and those without. METHODS: In this prospective study, blinded pathological analysis was performed on PAOM specimens from children who had surgery for CM-I and children who had surgery for posterior fossa tumors (controls). Clinical and radiographic data were collected. Statistical analysis included comparisons between the CM-I and control cohorts and correlations with imaging measures. RESULTS: A total of 35 children (mean age at surgery 10.7 years; 94.3% white) with viable specimens for evaluation were enrolled: 24 with CM-I and 11 controls. There were no statistical demographic differences between the two cohorts. Four children had a family history of CM-I and five had a syndromic condition. The cohorts had similar measurements of tonsillar descent, syringomyelia, basion to C2, and condylar-to-C2 vertical axis (all p>0.05). The clival-axial angle was lower in patients with CM-I (138.1 vs. 149.3 degrees, p = 0.016). Morphologically, the PAOM demonstrated statistically higher proportions of disorganized architecture in patients with CM-I (75.0% vs. 36.4%, p = 0.012). There were no differences in PAOM fat, elastin, or collagen percentages overall and no differences in imaging or ultrastructural findings between male and female patients. Posterior fossa volume was lower in children with CM-I (163,234 mm3 vs. 218,305 mm3, p<0.001), a difference that persisted after normalizing for patient height (129.9 vs. 160.9, p = 0.028). CONCLUSIONS: In patients with CM-I, the PAOM demonstrates disorganized architecture compared with that of control patients. This likely represents an anatomic adaptation in the presence of CM-I rather than a pathologic contribution.

Early, Persistent Lymphopenia Is Associated With Prolonged Multiple Organ Failure and Mortality in Septic Children.

OBJECTIVES: Sepsis-associated immune suppression correlates with poor outcomes. Adult trials are evaluating immune support therapies. Limited data exist to support consideration of immunomodulation in pediatric sepsis. We tested the hypothesis that early, persistent lymphopenia predicts worse outcomes in pediatric severe sepsis. DESIGN: Observational cohort comparing children with severe sepsis and early, persistent lymphopenia (absolute lymphocyte count < 1,000 cells/µL on 2 d between study days 0-5) to children without. The composite outcome was prolonged multiple organ dysfunction syndrome (MODS, organ dysfunction beyond day 7) or PICU mortality. SETTING: Nine PICUs in the National Institutes of Health Collaborative Pediatric Critical Care Research Network between 2015 and 2017. PATIENTS: Children with severe sepsis and indwelling arterial and/or central venous catheters. INTERVENTIONS: Blood sampling and clinical data analysis. MEASUREMENTS AND MAIN RESULTS: Among 401 pediatric patients with severe sepsis, 152 (38%) had persistent lymphopenia. These patients were older, had higher illness severity, and were more likely to have underlying comorbidities including solid organ transplant or malignancy. Persistent lymphopenia was associated with the composite outcome prolonged MODS or PICU mortality (66/152, 43% vs 45/249, 18%; p < 0.01) and its components prolonged MODS (59/152 [39%] vs 43/249 [17%]), and PICU mortality (32/152, 21% vs 12/249, 5%; p < 0.01) versus children without. After adjusting for baseline factors at enrollment, the presence of persistent lymphopenia was associated with an odds ratio of 2.98 (95% CI [1.85-4.02]; p < 0.01) for the composite outcome. Lymphocyte count trajectories showed that patients with persistent lymphopenia generally did not recover lymphocyte counts during the study, had lower nadir whole blood tumor necrosis factor-α response to lipopolysaccharide stimulation, and higher maximal inflammatory markers (C-reactive protein and ferritin) during days 0-3 ( p < 0.01). CONCLUSIONS: Children with severe sepsis and persistent lymphopenia are at risk of prolonged MODS or PICU mortality. This evidence supports testing therapies for pediatric severe sepsis patients risk-stratified by early, persistent lymphopenia.

Survival and Hemodynamics During Pediatric Cardiopulmonary Resuscitation for Bradycardia and Poor Perfusion Versus Pulseless Cardiac Arrest.

OBJECTIVES: The objective of this study was to compare survival outcomes and intra-arrest arterial blood pressures between children receiving cardiopulmonary resuscitation for bradycardia and poor perfusion and those with pulseless cardiac arrests. DESIGN: Prospective, multicenter observational study. SETTING: PICUs and cardiac ICUs of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Children (< 19 yr old) who received greater than or equal to 1 minute of cardiopulmonary resuscitation with invasive arterial blood pressure monitoring in place. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 164 patients, 96 (59%) had bradycardia and poor perfusion as the initial cardiopulmonary resuscitation rhythm. Compared to those with initial pulseless rhythms, these children were younger (0.4 vs 1.4 yr; p = 0.005) and more likely to have a respiratory etiology of arrest (p < 0.001). Children with bradycardia and poor perfusion were more likely to survive to hospital discharge (adjusted odds ratio, 2.31; 95% CI, 1.10-4.83; p = 0.025) and survive with favorable neurologic outcome (adjusted odds ratio, 2.21; 95% CI, 1.04-4.67; p = 0.036). There were no differences in diastolic or systolic blood pressures or event survival (return of spontaneous circulation or return of circulation via extracorporeal cardiopulmonary resuscitation). Among patients with bradycardia and poor perfusion, 49 of 96 (51%) had subsequent pulselessness during the cardiopulmonary resuscitation event. During cardiopulmonary resuscitation, these patients had lower diastolic blood pressure (point estimate, -6.68 mm Hg [-10.92 to -2.44 mm Hg]; p = 0.003) and systolic blood pressure (point estimate, -12.36 mm Hg [-23.52 to -1.21 mm Hg]; p = 0.032) and lower rates of return of spontaneous circulation (26/49 vs 42/47; p < 0.001) than those who were never pulseless. CONCLUSIONS: Most children receiving cardiopulmonary resuscitation in ICUs had an initial rhythm of bradycardia and poor perfusion. They were more likely to survive to hospital discharge and survive with favorable neurologic outcomes than patients with pulseless arrests, although there were no differences in immediate event outcomes or intra-arrest hemodynamics. Patients who progressed to pulselessness after cardiopulmonary resuscitation initiation had lower intra-arrest hemodynamics and worse event outcomes than those who were never pulseless.

Assessing Infrastructure to Care for Pediatric Patients in the Prehospital Setting.

OBJECTIVES: Pediatric patients represent a small proportion of emergency medical services (EMS) calls, challenging providers in maintaining skills in treating children. Having structural capacity to appropriately diagnose and treat pediatric patients is critical. Our study measured the availability of off-line and on-line medical direction and recommended pediatric equipment at EMS agencies. METHODS: A Web-based survey was sent to EMS agencies in 2010 and 2013, and results were analyzed to determine availability of medical direction and equipment. RESULTS: Approximately 5000 agencies in 32 states responded, representing over 80% response. Availability of off-line medical direction increased between years (78% in 2010 to 85% in 2013), was lower for basic life support (BLS) (63% and 72%) than advanced life support (ALS) agencies (90% and 93%), and was generally higher in urban than rural or frontier locations. On-line medical direction was consistently available (90% both years) with slight increases for BLS agencies (87% to 90%) and slightly greater availability for urban and rural compared with frontier agencies. The majority of agencies carried most recommended equipment; however, less than one third of agencies reported carrying all equipment. Agencies with off-line medical direction, on-line medical direction, and with both off-line and on-line medical direction were respectively 1.69, 1.31, and 2.21 times more likely to report carrying all recommended equipment. CONCLUSIONS: Basic structural capacity exists in EMS for treating children, with improvements seen over time. However, gaps remain, particularly for BLS and nonurban agencies. Continuous attention to infrastructure is necessary, and the recent development of national performance measures should further promote quality emergency care for all children.

The association of immediate post cardiac arrest diastolic hypertension and survival following pediatric cardiac arrest.

AIM: In-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0-20 min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge. METHODS: This is a secondary analysis of the Pediatric Intensive Care Quality of CPR (PICqCPR) study of invasively measured blood pressures during intensive care unit CPR. Patients were eligible if they achieved ROSC and had at least one invasively measured blood pressure within the first 20 min following ROSC. Post-ROSC blood pressures were normalized for age, sex and height. "Immediate hypertension" was defined as at least one systolic or diastolic blood pressure >90th percentile. The primary outcome was survival to hospital discharge. RESULTS: Of 102 children, 70 (68.6%) had at least one episode of immediate post-CPR diastolic hypertension. After controlling for pre-existing hypotension, duration of CPR, calcium administration, and first documented rhythm, patients with immediate post-CPR diastolic hypertension were more likely to survive to hospital discharge (79.3% vs. 54.5%; adjusted OR = 2.93; 95%CI, 1.16-7.69). CONCLUSIONS: In this post hoc secondary analysis of the PICqCPR study, 68.6% of subjects had diastolic hypertension within 20 min of ROSC. Immediate post-ROSC hypertension was associated with increased odds of survival to discharge, even after adjusting for covariates of interest.

The association of early post-resuscitation hypotension with discharge survival following targeted temperature management for pediatric in-hospital cardiac arrest.

AIM: Approximately 40% of children who have an in-hospital cardiac arrest (IHCA) in the US survive to discharge. We aimed to evaluate the impact of post-cardiac arrest hypotension during targeted temperature management following IHCA on survival to discharge. METHODS: This is a secondary analysis of the therapeutic hypothermia after pediatric cardiac arrest in-hospital (THAPCA-IH) trial. "Early hypotension" was defined as a systolic blood pressure less than the fifth percentile for age and sex for patients not treated with extracorporeal membrane oxygenation (ECMO) or a mean arterial pressure less than fifth percentile for age and sex for patients treated with ECMO during the first 6 h of temperature intervention. The primary outcome was survival to hospital discharge. RESULTS: Of 299 children, 142 (47%) patients did not receive ECMO and 157 (53%) received ECMO. Forty-two of 142 (29.6%) non-ECMO patients had systolic hypotension. Twenty-three of 157 (14.7%) ECMO patients had mean arterial hypotension. After controlling for confounders of interest, non-ECMO patients who had early systolic hypotension were less likely to survive to hospital discharge (40.5% vs. 72%; adjusted OR [aOR] 0.34; 95%CI, 0.12-0.93). There was no difference in survival to discharge by blood pressure groups for children treated with ECMO (30.4% vs. 49.3%; aOR = 0.60; 95%CI, 0.22-1.63). CONCLUSIONS: In this secondary analysis of the THAPCA-IH trial, in patients not treated with ECMO, systolic hypotension within 6 h of temperature intervention was associated with lower odds of discharge survival. Blood pressure groups in patients treated with ECMO were not associated with survival to discharge.

One-year cognitive and neurologic outcomes in survivors of paediatric extracorporeal cardiopulmonary resuscitation.

OBJECTIVE: To describe one-year cognitive and neurologic outcomes among extracorporeal cardiopulmonary resuscitation (ECPR) survivors enrolled in the Therapeutic Hypothermia after Paediatric Cardiac Arrest In-Hospital (THAPCA-IH) trial; and compare outcomes between survivors who received ECPR, later extracorporeal membrane oxygenation (ECMO), or no ECMO. METHODS: All children recruited to THAPCA-IH were comatose post-arrest. Neurobehavioral function was assessed by caregivers using the Vineland Adaptive Behaviour Scales, 2nd edition (VABS-II) at pre-arrest baseline and 12 months post-arrest. Age-appropriate cognitive performance measures (Mullen Scales of Early Learning or Wechsler Abbreviated Scale of Intelligence) and neurologic examinations were obtained 12 months post-arrest. VABS-II and cognitive performance measures were transformed to standard scores (mean = 100, SD = 15) with higher scores representing better performance. Only children with broadly normal pre-arrest function (VABS-II ≥70) were included in this analysis. RESULTS: One-year follow-up was attained for 127 survivors with pre-arrest VABS-II ≥70. Of these, 57 received ECPR, 14 received ECMO later in their course, and 56 did not receive ECMO. VABS-II assessments were completed at 12 months for 55 (96.5%) ECPR survivors, cognitive testing for 44 (77.2%) and neurologic examination for 47 (82.5%). At 12 months, 39 (70.9%) ECPR survivors had VABS-II scores ≥70. On cognitive testing, 24 (54.6%) had scores ≥70, and on neurologic examination, 28 (59.5%) had no/minimal to mild impairment. Cognitive and neurologic score distributions were similar between ECPR, later ECMO and no ECMO groups. CONCLUSIONS: Many ECPR survivors had favourable outcomes although impairments were common. ECPR survivors had similar outcomes to other survivors who were initially comatose post-arrest.

Transitions of Care: The Presence of Written Interfacility Transfer Guidelines and Agreements for Pediatric Patients.

OBJECTIVE: Every year, emergency medical services agencies transport approximately 150,000 pediatric patients between hospitals. During these transitions of care, patient safety may be affected and contribute to adverse events when important clinical information is missing, incomplete, or inaccurate. Written interfacility transfer policies are one way to standardize procedures and facilitate communication between the hospitals leading to improved patient safety and satisfaction for children and families. METHODS: We assessed the presence and components of written interfacility transfer guidelines and agreements for pediatric patients via a survey sent to US hospital emergency department (ED) nurse managers during 2010 and 2013. RESULTS: Although there was an increase in the presence of written interfacility transfer guidelines and agreements, a third of hospitals did not have either by 2013, and only 50% had guidelines with all recommended pediatric components. Hospitals with medium and low ED pediatric patient volumes were less likely to have written guidelines or agreements compared with hospitals with high volume. Hospitals with advanced pediatric resources, such as a pediatric emergency care coordinator or EDs designated approved for pediatrics, were more likely to have guidelines or agreements than less resourced hospitals. CONCLUSIONS: Although there was improvement over time, opportunities exist for increasing the presence of written interfacility transfer guidelines as well as agreements for pediatric patients. Further studies are needed to demonstrate whether improved delivery of patient care is associated with the presence of written interfacility transfer guidelines and agreements and to identify other elements in the process to ensure optimal pediatric patient care.

Extracorporeal Cardiopulmonary Resuscitation: One-Year Survival and Neurobehavioral Outcome Among Infants and Children With In-Hospital Cardiac Arrest.

OBJECTIVE: To describe neurobehavioral outcomes and investigate factors associated with survival and survival with good neurobehavioral outcome 1 year after in-hospital cardiac arrest for children who received extracorporeal cardiopulmonary resuscitation. DESIGN: Secondary analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital trial. SETTING: Thirty-seven PICUs in the United States, Canada, and the United Kingdom. PATIENTS: Children (n = 147) resuscitated with extracorporeal cardiopulmonary resuscitation following in-hospital cardiac arrest. INTERVENTIONS: Neurobehavioral status was assessed using the Vineland Adaptive Behavior Scales, Second Edition, at prearrest baseline and 12 months postarrest. Norms for Vineland Adaptive Behavior Scales, Second Edition, are 100 (mean) ± 15 (SD). Higher scores indicate better functioning. Outcomes included 12-month survival, 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points from baseline, and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. MEASUREMENTS AND MAIN RESULTS: Of 147 children receiving extracorporeal cardiopulmonary resuscitation, 125 (85.0%) had a preexisting cardiac condition, 75 (51.0%) were postcardiac surgery, and 84 (57.1%) were less than 1 year old. Duration of chest compressions was greater than 30 minutes for 114 (77.5%). Sixty-one (41.5%) survived to 12 months, 32 (22.1%) survived to 12 months with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points from baseline, and 39 (30.5%) survived to 12 months with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. On multivariable analyses, open-chest cardiac massage was independently associated with greater 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points and greater 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. Higher minimum postarrest lactate and preexisting gastrointestinal conditions were independently associated with lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points and lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. CONCLUSIONS: About one third of children survived with good neurobehavioral outcome 1 year after receiving extracorporeal cardiopulmonary resuscitation for in-hospital arrest. Open-chest cardiac massage and minimum postarrest lactate were associated with survival with good neurobehavioral outcome at 1 year.

Open-label, add-on trial of cetirizine for neuromyelitis optica.

OBJECTIVE: This pilot study preliminarily examined the efficacy and tolerability of cetirizine as an add-on to standard therapy for neuromyelitis optica (NMO). METHODS: Eligible participants met the Wingerchuk 2006 diagnostic criteria or had a single typical episode along with positive NMO immunoglobulin G. After baseline clinical and laboratory assessments, participants began treatment with cetirizine 10 mg orally daily, in addition to their usual disease-modifying therapy for NMO, and continued for 1 year. The primary end point was the annualized relapse rate (ARR) while on the same disease-modifying therapy before starting cetirizine compared with after taking cetirizine. Additional end points included disability (Expanded Disability Status Scale [EDSS]), relapse severity, tolerability, especially with respect to drowsiness measured by the Epworth Sleepiness Scale (ESS), and laboratory parameters. RESULTS: The ARR before cetirizine was 0.4 ± 0.80 and after cetirizine was 0.1 ± 0.24 (p = 0.047). There was no statistically significant difference in the EDSS (mean 3.9 ± 2.18 before the start of the study and 3.2 ± 2.31 at the conclusion of the study, p = 0.500). The ESS remained fairly consistent throughout the study (mean 6.5 ± 5.33 at baseline and 6.9 ± 4.50 at month 12, p = 0.740). Laboratory studies were unrevealing. CONCLUSIONS: In this pilot study, cetirizine was well tolerated, and the prespecified primary efficacy end point was satisfied. However, the open-label design and the small sample size of this pilot study preclude definitive conclusions. Further research is needed. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with NMO, the addition of cetirizine to standard therapy is safe, well tolerated, and reduces relapses.

Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized controlled trials.

BACKGROUND: Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes. METHODS: Combine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48 h up to 18 years old, who remained comatose after resuscitation, were randomized within 6 h of return of circulation to hypothermia or normothermia (target 33.0 °C or 36.8 °C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean = 100, SD = 15), was evaluated among patients with pre-arrest scores ≥70. RESULTS: 624 patients were randomized. Among 517 with pre-arrest VABS-II scores ≥70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28% [75/271] and 26% [63/246], respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p = 0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p = 0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups. CONCLUSIONS: Analysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.

Neurologic outcomes in pediatric cardiac arrest survivors enrolled in the THAPCA trials.

OBJECTIVE: To implement a standardized approach to characterize neurologic outcomes among 12-month survivors in the Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) trials. METHODS: Two multicenter trials enrolled children age 48 hours to 18 years who remained comatose after cardiac arrest (CA) occurring out-of-hospital (THAPCA-OH, NCT00878644) or in-hospital (THAPCA-IH, NCT00880087); patients were randomized to therapeutic hypothermia or therapeutic normothermia. The primary outcome, survival with favorable 12-month neurobehavioral outcome (Vineland Adaptive Behavior Scales [VABS-II]), did not differ between treatment groups in either trial. Neurologists examined 181 12-month survivors, described findings using the novel semi-quantitative Pediatric Resuscitation after Cardiac Arrest (PRCA) form, and rated findings in 6 domains; scores ranged from 0 (no deficits) to 21 (maximal deficits). PRCA scores were compared with 12-month VABS-II scores and cognitive scores. RESULTS: Neurologic outcome PRCA scores were classified as no/minimal impairment, PRCA 0-3, 81/179 (45%); mild impairment, PRCA 4-7, 24/179 (13%); moderate impairment, PRCA 8-11, 15/179 (8%); severe impairment, PRCA 12-16, 20/179 (11%); profound impairment, PRCA 17-21, 39/179 (21%) (2/181 incomplete). VABS-II scores correlated strongly with PRCA category (r = -0.88, p < 0.0001, Pearson correlation coefficient) and cognitive scores (r = -0.72, p < 0.0001). Factors associated with poor outcomes included out-of-hospital CA, seizure recognition in the early postarrest period, and poor neurologic status at hospital discharge. CONCLUSION: The PRCA provides a robust method for depicting neurologic outcomes after acute encephalopathy caused by CA in children. It provides a global semiquantitative rating of neurologic impairment and domain-specific impairment. The strong correlation with well-established neurobehavioral outcome measures supports its validity over a broad age range and wide spectrum of outcomes.

Burden of caregiving after a child's in-hospital cardiac arrest.

OBJECTIVE: To describe caregiver burden among those whose children survive in-hospital cardiac arrest and have high risk of neurologic disability, and explore factors associated with burden during the first year post-arrest. METHODS: The study is a secondary analysis of the Therapeutic Hypothermia after Paediatric Cardiac Arrest In-Hospital (THAPCA-IH) trial. 329 children who had an in-hospital cardiac arrest, chest compressions for >2 min, and mechanical ventilation after return of circulation were recruited to THAPCA-IH. Of these, 155 survived to one year, and caregivers of 138 were assessed for burden. Caregiver burden was assessed at baseline, and 3 and 12 months post-arrest using the Infant Toddler Quality of Life Questionnaire for children <5 years old and the Child Health Questionnaire for children >5 years. Child functioning was assessed using the Vineland Adaptive Behaviour Scales Second Edition (VABS-II), the Paediatric Overall Performance Category (POPC) and Paediatric Cerebral Performance Category (PCPC) scales, and caregiver perception of global functioning. RESULTS: Of 138 children, 77 (55.8%) were male, 77 (55.8%) were white, and 109 (79.0%) were <5 years old at the time of arrest. Caregiver burden was greater than reference norms at all time points. Worse POPC, PCPC and VABS-II scores at 3 months post-arrest were associated with greater caregiver burden at 12 months. Worse global functioning at 3 months was associated with greater burden at 12 months for children <5 years. CONCLUSIONS: Caregiver burden is substantial during the first year after paediatric in-hospital cardiac arrest, and associated with the extent of the child's neurobehavioural dysfunction.

Paediatric in-hospital cardiac arrest: Factors associated with survival and neurobehavioural outcome one year later.

OBJECTIVE: To investigate clinical characteristics associated with 12-month survival and neurobehavioural function among children recruited to the Therapeutic Hypothermia after Paediatric Cardiac Arrest In-Hospital trial. METHODS: Children (n = 329) with in-hospital cardiac arrest who received chest compressions for ≥2 min, were comatose, and required mechanical ventilation after return of circulation were included. Neurobehavioural function was assessed using the Vineland Adaptive Behaviour Scales, second edition (VABS-II) at baseline (reflecting pre-arrest status) and 12 months post-arrest. Norms for VABS-II are 100 (mean) ±15 (SD). Higher scores indicate better functioning. Outcomes included 12-month survival, 12-month survival with VABS-II decreased by ≤15 points from baseline, and 12-month survival with VABS-II ≥70. RESULTS: Asystole as the initial arrest rhythm, administration of >4 adrenaline doses, and higher post-arrest blood lactate concentration were independently associated with lower 12-month survival; an adrenaline dosing interval of 3-<5 min and open chest compressions were independently associated with greater 12-month survival. Use of extracorporeal membrane oxygenation (ECMO) and higher blood lactate were independently associated with lower 12-month survival with VABS-II decreased by ≤15 points from baseline; open chest compressions was independently associated with greater 12-month survival with VABS-II decreased by ≤15 points. Asystole as the initial rhythm, use of ECMO, and higher blood lactate were independently associated with lower 12-month survival with VABS-II ≥70; open chest compressions was independently associated with greater 12-month survival with VABS-II ≥70. CONCLUSIONS: Cardiac arrest and resuscitation factors are associated with long-term survival and neurobehavioural function among children who are comatose after in-hospital arrest.

Neurobehavioural outcomes in children after In-Hospital cardiac arrest.

AIM: Children who remain comatose after in-hospital cardiac arrest (IH-CA) resuscitation are at risk for poor neurological outcome. We report results of detailed neurobehavioural testing in paediatric IH-CA survivors, initially comatose after return of circulation, and enrolled in THAPCA-IH, a clinical trial that evaluated two targeted temperature management interventions (hypothermia, 33.0 °C or normothermia, 36.8 °C; NCT00880087). METHODS: Children, aged 2 days to <18 years, were enrolled in THAPCA-IH from 2009 to 2015; primary trial outcome (survival with favorable neurobehavioural outcome) did not differ between groups. Pre-IH-CA neurobehavioural functioning, measured with the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) was evaluated soon after enrollment; this report includes only children with broadly normal pre-IH-CA scores (VABS-II composite scores ≥70; 269 enrolled). VABS-II was re-administered 3 and 12 months later. Cognitive testing was completed at 12 months. RESULTS: Follow-ups were obtained on 125 of 135 eligible one-year survivors. Seventy-seven percent (96/125) had VABS-II scores ≥70 at 12 months; cognitive composites were ≥2SD of mean in 59%. VABS-II composite, domain, and most subdomain scores declined between pre-IH-CA and 3-month, and pre-IH-CA and 12-month assessments (composite means declined about 1 SD at 3 and 12 months, p < 0.005); 3 and 12-month scores were strongly correlated (r = 0.72, p < 0.001). CONCLUSIONS: In paediatric IH-CA survivors at high risk for unfavorable outcomes, the majority demonstrated significant declines in neurobehavioural functioning, across multiple functional domains, with similar functioning at 3 and 12 months. About three-quarters attained VABS-II functional performance composite scores within the broadly normal range.

Viral DNAemia and Immune Suppression in Pediatric Sepsis.

OBJECTIVES: Demonstrate that DNA viremia is common in pediatric sepsis and quantitate its associations with host immune function and secondary infection risk. DESIGN: Retrospective analysis of a prospective cohort study. PATIENTS: Seventy-three children admitted with sepsis-induced organ failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study was performed as an ancillary investigation to a single-center prospective study of children with severe sepsis. Longitudinally collected, batched, frozen plasma was examined using real time-polymerase chain reaction for the presence of cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human herpes virus-6, torque teno virus, and adenovirus DNA. Innate immune function was also measured longitudinally via quantification of ex vivo lipopolysaccharide -induced tumor necrosis factor-α production capacity. Viral DNAemia with a virus other than torque teno virus was detected in 28 of 73 subjects (38%) and included cytomegalovirus 5%, Epstein-Barr virus 11%, herpes simplex virus 4%, human herpes virus-6 8%, and adenovirus 26%. In addition, torque teno virus was detected in 89%. Epstein-Barr virus DNAemia was associated with preexisting immune suppression (p = 0.007) Viral DNAemia was associated with preexisting immune suppression and high risk for the subsequent development of secondary infection (p < 0.05 for both). Subjects with viral DNAemia had lower innate immune function over time compared with those who were virus negative (p < 0.05). CONCLUSIONS: DNAemia from multiple viruses can be detected in septic children and is strongly associated with preexisting immune suppression and secondary infection risk. The role of DNA viruses in the perpetuation of impaired host defense in this setting should be the subject of prospective study.

Association of Early Postresuscitation Hypotension With Survival to Discharge After Targeted Temperature Management for Pediatric Out-of-Hospital Cardiac Arrest: Secondary Analysis of a Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest (OHCA) occurs in more than 6000 children each year in the United States, with survival rates of less than 10% and severe neurologic morbidity in many survivors. Post-cardiac arrest hypotension can occur, but its frequency and association with survival have not been well described during targeted temperature management. Objective: To determine whether hypotension is associated with survival to discharge in children and adolescents after resuscitation from OHCA. Design, Setting, and Participants: This post hoc secondary analysis of the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trial included 292 pediatric patients older than 48 hours and younger than 18 years treated in 36 pediatric intensive care units from September 1, 2009, through December 31, 2012. Participants underwent therapeutic hypothermia (33.0°C) vs therapeutic normothermia (36.8°C) for 48 hours. All participants had hourly systolic blood pressure measurements documented during the initial 6 hours of temperature intervention. Hourly blood pressures beginning at the time of temperature intervention (time 0) were normalized for age, sex, and height. Early hypotension was defined as a systolic blood pressure less than the fifth percentile during the first 6 hours after temperature intervention. With use of forward stepwise logistic regression, covariates of interest (age, sex, initial cardiac rhythm, any preexisting condition, estimated duration of cardiopulmonary resuscitation [CPR], primary cause of cardiac arrest, temperature intervention group, night or weekend cardiac arrest, witnessed status, and bystander CPR) were evaluated in the final model. Data were analyzed from February 5, 2016, through June 13, 2017. Exposures: Hypotension. Main Outcomes and Measure: Survival to hospital discharge. Results: Of 292 children (194 boys [66.4%] and 98 girls [33.6%]; median age, 23.0 months [interquartile range, 5.0-105.0 months]), 78 (26.7%) had at least 1 episode of early hypotension. No difference was observed between the therapeutic hypothermia and therapeutic normothermia groups in the prevalence of hypotension during induction and maintenance (73 of 153 [47.7%] vs 72 of 139 [51.8%]; P = .50) or rewarming (35 of 118 [29.7%] vs 19 of 95 [20.0%]; P = .10) during the first 72 hours. Participants who had early hypotension were less likely to survive to hospital discharge (20 of 78 [25.6%] vs 93 of 214 [43.5%]; adjusted odds ratio, 0.39; 95% CI, 0.20-0.74). Conclusions and Relevance: In this post hoc secondary analysis of the THAPCA trial, 26.7% of participants had hypotension within 6 hours after temperature intervention. Early post-cardiac arrest hypotension was associated with lower odds of discharge survival, even after adjusting for covariates of interest.

Ticketing aggressive cars and trucks (TACT): How does it work on city streets?

OBJECTIVE: The purpose of this study was to determine the feasibility of modifying the Ticking Aggressive Cars and Trucks (TACT) program, originally designed to work on state highways, within a metropolitan area to reduce unsafe interactions and their related crashes between drivers of large trucks and passenger vehicles. METHODS: Using crash data, the driving behaviors most commonly associated with large truck and passenger vehicle crashes were identified. A public awareness campaign using media messaging and increased law enforcement was created targeting these associated behaviors. The frequency of these behaviors both before and after the public awareness campaign was determined through observation of traffic at 3 specific locations within the city. Each location had a sufficient volume of large truck and passenger traffic to observe frequent interactions. Pre- and postintervention data were compared using negative binomial regression with generalized estimating equations to evaluate whether the campaign was associated with a reduction in the identified driving behaviors. RESULTS: A comparison between crash data from before, during, and after the campaign and crashes during the same time periods in previous years did not show a significant difference (P =.081). The number of large trucks observed in traffic remained the same during pre- and postintervention periods (P =.625). The rates of negative interactions per 100 large trucks decreased for both large trucks and passenger vehicles after the intervention, with calculated rate ratios of 0.58 (95% confidence interval [CI], 0.48, 0.70) and 0.31 (95% CI, 0.20, 0.47). The greatest reduction was seen in passenger vehicles following too close, with a rate ratio of 0.21 (95% CI, 0.15, 0.30). CONCLUSIONS: Although designed for reducing crashes on highways, the TACT program can be an effective approach for improving driver behaviors on city streets.

Pediatric cardiac arrest due to drowning and other respiratory etiologies: Neurobehavioral outcomes in initially comatose children.

AIM: To describe the 1-year neurobehavioral outcome of survivors of cardiac arrest secondary to drowning, compared with other respiratory etiologies, in children enrolled in the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial. METHODS: Exploratory analysis of survivors (ages 1-18 years) who received chest compressions for ≥2min, were comatose, and required mechanical ventilation after return of circulation (ROC). Participants recruited from 27 pediatric intensive care units in North America received targeted temperature management [therapeutic hypothermia (33°C) or therapeutic normothermia (36.8°C)] within 6h of ROC. Neurobehavioral outcomes included 1-year Vineland Adaptive Behavior Scales, Second Edition (VABS-II) total and domain scores and age-appropriate cognitive performance measures (Mullen Scales of Early Learning or Wechsler Abbreviated Scale of Intelligence). RESULTS: Sixty-six children with a respiratory etiology of cardiac arrest survived for 1-year; 60/66 had broadly normal premorbid functioning (VABS-II≥70). Follow up was obtained on 59/60 (30 with drowning etiology). VABS-II composite and domain scores declined significantly from premorbid scores in drowning and non-drowning groups (p<0.001), although declines were less pronounced for the drowning group. Seventy-two percent of children had well below average cognitive functioning at 1-year. Younger age, fewer doses of epinephrine, and drowning etiology were associated with better VABS-II composite scores. Demographic variables and treatment with hypothermia did not influence neurobehavioral outcomes. CONCLUSIONS: Risks for poor neurobehavioral outcomes were high for children who were comatose after out-of-hospital cardiac arrest due to respiratory etiologies; survivors of drowning had better outcomes than those with other respiratory etiologies.

Pediatric Readiness in Indian Health Service and Tribal Emergency Departments: Results from the National Pediatric Readiness Project.

INTRODUCTION: In 2014, 45 Indian Health Service (IHS)/Tribal emergency departments serving American Indian and Alaskan Native communities treated approximately 650,000 patients of which, 185,000 (28%) were children and youth younger than 19 years. This study presents the results of the National Pediatric Readiness Project (NPRP) assessment of the 45 IHS/Tribal emergency departments. METHODS: Data were obtained from the 2013 NPRP national assessment, which is a 55-question Web-based questionnaire based on previously published 2009 national consensus guidelines. The main measure of readiness is the weighted pediatric readiness score (WPRS), with the highest score being 100. RESULTS: The overall mean WPRS for all emergency departments is 60.9. Of the IHS/Tribal emergency departments that had pediatric emergency care coordinators, scores across all domains were higher than those of emergency departments without pediatric emergency care coordinators. All 45 emergency departments have readily available a pediatric medication dosing chart, length-based tape, medical software, or other system to ensure proper sizing of resuscitation equipment and proper dosing of medication. Of the 45 IHS/Tribal 37% report having 100% of the equipment items, and 78% report having at least 80% of these items. DISCUSSION: This article reports the results of the NPRP assessment in IHS/Tribal emergency departments that, despite serving a historically vulnerable population, scored favorably when compared with national data. The survey identified areas for improvement, including implementation of QI processes, stocking of pediatric specific equipment, implementation of policies and procedures on interfacility transport, and maintaining staff pediatric competencies.