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Objectives To describe telephone interview completion rates among 12-month cardiac arrest survivors enrolled in the Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital and Out-of-Hospital trials, identify key characteristics of the completed follow-up interviews at both 3- and 12-month postcardiac arrest, and describe strategies implemented to promote follow-up. Setting Centralized telephone follow-up interviews. Design Retrospective report of data collected for Therapeutic Hypothermia after Pediatric Cardiac Arrest trials, and summary of strategies used to maximize follow-up completion. Patients Twelve-month survivors (n = 251) from 39 Therapeutic Hypothermia after Pediatric Cardiac Arrest PICU sites in the United States, Canada, and United Kingdom. Interventions Not applicable. Measurements and main results The 3- and 12-month telephone interviews included completion of the Vineland Adaptive Behavior Scales, Second Edition. Vineland Adaptive Behavior Scales, Second Edition data were available on 96% of 3-month survivors (242/251) and 95% of 12-month survivors (239/251) with no differences in demographics between those with and without completed Vineland Adaptive Behavior Scales, Second Edition. At 12 months, a substantial minority of interviews were completed with caregivers other than parents (10%), after calls attempts were made on 6 or more days (18%), and during evenings/weekends (17%). Strategies included emphasizing the relationship between study teams and participants, ongoing communication between study team members across sites, promoting site engagement during the study's final year, and withholding payment for work associated with the primary outcome until work had been completed. Conclusions It is feasible to use telephone follow-up interviews to successfully collect detailed neurobehavioral outcome about children following pediatric cardiac arrest. Future studies should consider availability of the telephone interviewer to conduct calls at times convenient for families, using a range of respondents, ongoing engagement with site teams, and site payment related to primary outcome completion.

To determine associations between anticoagulation practices and bleeding and thrombosis during pediatric extracorporeal membrane oxygenation (ECMO), we performed a secondary analysis of prospectively collected data which included 481 children (80 ml/kg on any day, pulmonary hemorrhage, or intracranial bleeding, Thrombotic events included pulmonary emboli, intracranial clot, limb ischemia, cardiac clot, and arterial cannula or entire circuit change. Bleeding occurred in 42% of patients. Five percent of subjects thrombosed, of which 89% also bled. Daily bleeding odds were independently associated with day prior activated clotting time (ACT) (OR 1.03, 95% CI= 1.00, 1.05, p=0.047) and fibrinogen levels (OR 0.90, 95% CI 0.84, 0.96, p

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.

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.

Background Limited data exist about neurobehavioral outcomes of children treated with open-chest cardiopulmonary resuscitation (CPR). Our objective was to describe neurobehavioral outcomes 1 year after arrest among children who received open-chest CPR during in-hospital cardiac arrest and to explore factors associated with 1-year survival and survival with good neurobehavioral outcome. Methods The study is a secondary analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital Trial. Fifty-six children who received open-chest CPR for in-hospital cardiac arrest were included. Neurobehavioral status was assessed using the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at baseline before arrest and 12 months after arrest. Norms for VABS-II are 100 ± 15 points. Outcomes included 12-month survival, 12-month survival with VABS-II decreased by no more than 15 points from baseline, and 12-month survival with VABS-II of 70 or more points. Results Of 56 children receiving open-chest CPR, 49 (88%) were after cardiac surgery and 43 (77%) were younger than 1 year. Forty-four children (79%) were cannulated for extracorporeal membrane oxygenation (ECMO) during CPR or within 6 hours of return of spontaneous circulation. Thirty-three children (59%) survived to 12 months, 22 (41%) survived to 12 months with VABS-II decreased by no more than 15 points from baseline, and of the children with baseline VABS-II of 70 or more points 23 (51%) survived to 12 months with VABS-II of 70 or more points. On multivariable analyses, use of ECMO, renal replacement therapy, and higher maximum international normalized ratio were independently associated with lower 12-month survival with VABS-II of 70 or more points. Conclusions Approximately one-half of children survived with good neurobehavioral outcome 1 year after open-chest CPR for in-hospital cardiac arrest. Use of ECMO and postarrest renal or hepatic dysfunction may be associated with worse neurobehavioral outcomes.

This study evaluates whether three commonly used pediatric intensive care unit (PICU) severity of illness scores, pediatric risk of mortality score (PRISM) III, pediatric index of mortality (PIM) 2, and pediatric logistic organ dysfunction (PELOD), are the appropriate tools to discriminate mortality risk in children receiving extracorporeal membrane oxygenation (ECMO) support for respiratory failure. This study also evaluates the ability of the Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support (Ped-RESCUERS) to discriminate mortality risk in the same population, and whether Ped-RESCUERS' discrimination of mortality is improved by additional clinical and laboratory measures of renal, hepatic, neurologic, and hematologic dysfunction. A multi-institutional retrospective cohort study was conducted on children aged 29 days to 17 years with respiratory failure requiring respiratory ECMO support. Discrimination of mortality was evaluated with the area under the receiver operating curve (AUC); model calibration was measured by the Hosmer-Lemeshow goodness of fit test and Brier score. Admission PRISM-III, PIM-2, and PELOD were found to have poor ability to discriminate mortality with an AUC of 0.56 [0.46-0.66], 0.53 [0.43-0.62], and 0.57 [0.47-0.67], respectively. Alternatively, Ped-RESCUERS performed better with an AUC of 0.68 [0.59-0.77]. Higher alanine aminotransferase, ratio of the arterial partial pressure of oxygen the fraction of inspired oxygen, and lactic acidosis were independently associated with mortality and, when added to Ped-RESCUERS, resulted in an AUC of 0.75 [0.66-0.82]. Admission PRISM-III, PIM-2, and PELOD should not be used for pre-ECMO risk adjustment because they do not discriminate death. Extracorporeal membrane oxygenation population-derived scores should be used to risk adjust ECMO populations as opposed to general PICU population-derived scores.

AIM: Although recent out-of-hospital cardiac arrest (CA) trials found no benefits of hypothermia versus normothermia targeted temperature management, preclinical models suggest earlier timing of hypothermia improves neuroprotective efficacy. This study investigated whether shorter time to goal temperature was associated with better one-year outcomes in the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital Trial METHODS: Patients were classified by tertiles of time to attain assigned goal temperature range (32–34°C or 36–37.5°C) following ROSC. Outcomes in the first tertile (“earlier”) Group 1 were compared with second and third tertiles (“later”) Group 2. Separate analyses were, additionally, completed for hypothermia and normothermia intervention groups. Three one-year outcomes were examined: survival; Vineland Adaptive Behavior Scale (VABS-II) score ≥70; and decrease in VABS-II ≤15 points from baseline. RESULTS: In the entire cohort (n=281), median time from ROSC to goal temperature was 7.4 [IQR 6.2–9.7] hours: Group 1, 5.8 [IQR 5.2, 6.2] and Group 2, 8.8 [IQR 7.4, 10.4] hours. Outcomes did not differ between these groups. For hypothermia subgroup, survival was lower in Group 1 than 2, [10/49(20%) versus 47/99(47%), p

Aim Determine 1) frequency and risk factors for acute kidney injury (AKI) after in-hospital cardiac arrest (IHCA) in the Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) trial and associated outcomes; 2) impact of temperature management on post-IHCA AKI. Methods Secondary analysis of THAPCA-IH; a randomized controlled multi-national trial at 37 children’s hospitals. Eligibility Serum creatinine (Cr) within 24 h of randomization. Outcomes Prevalence of severe AKI defined by Stage 2 or 3 Kidney Disease Improving Global Outcomes Cr criteria. 12-month survival with favorable neurobehavioral outcome. Analyses stratified by entire cohort and cardiac subgroup. Risk factors and outcomes compared among cohorts with and without severe AKI. Results Subject randomization: 159 to hypothermia, 154 to normothermia. Overall, 80% (249) developed AKI (any stage), and 66% (207) developed severe AKI. Cardiac patients (204, 65%) were more likely to develop severe AKI (72% vs 56%,p = 0.006). Preexisting cardiac or renal conditions, baseline lactate, vasoactive support, and systolic blood pressure were associated with severe AKI. Comparing hypothermia versus normothermia, there were no differences in severe AKI rate (63% vs 70%,p = 0.23), peak Cr, time to peak Cr, or freedom from mortality or severe AKI (p = 0.14). Severe AKI was associated with decreased hospital survival (48% vs 65%,p = 0.006) and decreased 12-month survival with favorable neurobehavioral outcome (30% vs 53%,p Conclusion Severe post-IHCA AKI occurred frequently especially in those with preexisting cardiac or renal conditions and peri-arrest hemodynamic instability. Severe AKI was associated with decreased survival with favorable neurobehavioral outcome. Hypothermia did not decrease incidence of severe AKI post-IHCA.

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.

INTRODUCTION: Patients who suffer in-hospital cardiac arrest (IHCA) are less likely to survive if the arrest occurs during nighttime versus daytime. Diastolic blood pressure (DBP) as a measure of chest compression quality was associated with survival from pediatric IHCA. We hypothesized that DBP during CPR for IHCA is lower during nighttime versus daytime. METHODS: This is a secondary analysis of data collected from the Pediatric Intensive Care Quality of Cardiopulmonary Resuscitation Study. Pediatric or Pediatric Cardiac Intensive Care Unit patients who received chest compressions for ≥1 minute and who had invasive arterial BP monitoring were enrolled. Nighttime was defined as 11:00PM to 6:59AM and daytime as 7:00AM until 10:59PM. Primary outcome was attainment of DBP ≥25 mmHg in infants

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.

IMPORTANCE: Many children with return of spontaneous circulation (ROSC) following cardiac arrest (CA) experience acute kidney injury (AKI). The impact of therapeutic hypothermia on the epidemiology of post-CA AKI in children has not been fully investigated. OBJECTIVE: The study aims were to: 1) describe the prevalence of severe AKI in comatose children following out-of-hospital CA (OHCA), 2) identify risk factors for severe AKI, 3) evaluate the impact of therapeutic hypothermia on the prevalence of severe AKI, and 4) evaluate the association of severe AKI with survival and functional outcomes. DESIGN: A post hoc secondary analysis of data from the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial. SETTING: Thirty-six pediatric intensive care units in the United States and Canada. PARTICIPANTS: Of 282 eligible subjects with an initial creatinine obtained within 24 hours of randomization, 148 were randomized to therapeutic hypothermia and 134 were randomized to therapeutic normothermia. MAIN OUTCOMES AND MEASURES: Primary outcome was prevalence of severe AKI, as defined by stage 2 and 3 Kidney Disease Improving Global Outcomes (KDIGO) consensus definition; secondary outcome was survival with a favorable neurobehavioral outcome. For this study, risk factors and outcomes were compared between those with/without severe AKI. RESULTS: Of the 282 subjects enrolled, 180 (64%) developed AKI of which 117 (41% of all enrolled) developed severe AKI. Multivariable modeling found younger age, longer duration of chest compressions, higher lactate level at time of temperature intervention and higher number of vasoactive agents through day 1 of intervention associated with severe AKI. There was no difference in severe AKI between therapeutic hypothermia (39.9%) and therapeutic normothermia (43.3%) groups (p=0.629). Survival was lower in those with severe AKI at 28 days (21% vs no severe AKI 49%, p

AIM: The primary aim of this study was to evaluate the association between chest compression rates and 1) arterial blood pressure and 2) survival outcomes during pediatric in-hospital cardiopulmonary resuscitation (CPR). METHODS: Prospective observational study of children ≥37 weeks gestation and 120–140, >140) and outcomes. RESULTS: Compression rate data were available for 164 patients. More than half (98/164; 60%) were < 1 year old. Return of circulation was achieved in 148/164 (90%); survival to hospital discharge in 77/164 (47%). Percentage of events with average rate within Guidelines was 32.9%. Compared to Guidelines, higher rate categories were associated with lower systolic blood pressures (>120–140, p=0.010; >140, p=0.077), but not survival. A rate between 80

The Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) Trial showed therapeutic hypothermia, versus normothermia, did not significantly improve 1-year survival with good neurobehavioral outcome. Our survey of pediatric critical care physicians, designed to assess the use of targeted temperature management (TTM) after publication of the main THAPCA-OH Trial results, found most respondents were aware of trial results, and over 90% agreed THAPCA-OH was well-designed with important clinical outcomes. While most respondents reported TTM usage consistent with THAPCA-OH results in different patient scenarios, 15% did not select TTM for fever management. Since trials prior to THAPCA-OH established that fever is harmful following brain injury, the continued incomplete adoption of TTM warrants further research on challenges and facilitators to the adoption of clinical trial findings.

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

Although pediatric intensivists philosophically embrace lung protective ventilation for acute lung injury and acute respiratory distress syndrome, we hypothesized that ventilator management varies. We assessed ventilator management by evaluating changes to ventilator settings in response to blood gases, pulse oximetry, or end-tidal CO2. We also assessed the potential impact that a pediatric mechanical ventilation protocol adapted from National Heart Lung and Blood Institute acute respiratory distress syndrome network protocols could have on reducing variability by comparing actual changes in ventilator settings to those recommended by the protocol.Prospective observational study.Eight tertiary care U.S. PICUs, October 2011 to April 2012.One hundred twenty patients (age range 17 d to 18 yr) with acute lung injury/acute respiratory distress syndrome.Two thousand hundred arterial and capillary blood gases, 3,964 oxygen saturation by pulse oximetry, and 2,757 end-tidal CO2 values were associated with 3,983 ventilator settings. Ventilation mode at study onset was pressure control 60%, volume control 19%, pressure-regulated volume control 18%, and high-frequency oscillatory ventilation 3%. Clinicians changed FIO2 by ±5 or ±10% increments every 8 hours. Positive end-expiratory pressure was limited at ~10 cm H2O as oxygenation worsened, lower than would have been recommended by the protocol. In the first 72 hours of mechanical ventilation, maximum tidal volume/kg using predicted versus actual body weight was 10.3 (8.5-12.9) (median [interquartile range]) versus 9.2 mL/kg (7.6-12.0) (p0.001). Intensivists made changes similar to protocol recommendations 29% of the time, opposite to the protocol's recommendation 12% of the time and no changes 56% of the time.Ventilator management varies substantially in children with acute respiratory distress syndrome. Opportunities exist to minimize variability and potentially injurious ventilator settings by using a pediatric mechanical ventilation protocol offering adequately explicit instructions for given clinical situations. An accepted protocol could also reduce confounding by mechanical ventilation management in a clinical trial.

Objectives To examine issues regarding the granularity (size/scale) and potential acceptability of recommendations in a ventilator management protocol for children with pediatric acute respiratory distress syndrome. Design Survey/questionnaire. Setting The eight PICUs in the Collaborative Pediatric Critical Care Research Network. Participants One hundred twenty-two physicians (attendings and fellows). Interventions None. Measurements and main results We used an online questionnaire to examine attitudes and assessed recommendations with 50 clinical scenarios. Overall 80% of scenario recommendations were accepted. Acceptance did not vary by provider characteristics but did vary by ventilator mode (high-frequency oscillatory ventilation 83%, pressure-regulated volume control 82%, pressure control 75%; p = 0.002) and variable adjusted (ranging from 88% for peak inspiratory pressure and 86% for FIO2 changes to 69% for positive end-expiratory pressure changes). Acceptance did not vary based on child size/age. There was a preference for smaller positive end-expiratory pressure changes but no clear granularity preference for other variables. Conclusions Although overall acceptance rate for scenarios was good, there was little consensus regarding the size/scale of ventilator setting changes for children with pediatric acute respiratory distress syndrome. An acceptable protocol could support robust evaluation of ventilator management strategies. Further studies are needed to determine if adherence to an explicit protocol leads to better outcomes.

Objective:Pediatric extracorporeal membrane oxygenation (ECMO) varies in the way care is provided from hospital to hospital. This variability in hospital ECMO care can be represented by the variation in ECMO costs. We hypothesized that hospitals will demonstrate large variations in case-mix-adjusted ECMO inpatient costs for children requiring ECMO and higher volume hospitals will have lower associated costs.Methods:We retrospectively analyzed the inpatient cost of children receiving ECMO in 2006, 2009 and 2012, using the Healthcare Cost and Utilization Project Kids’ Inpatient Database. We used a hierarchical linear regression model and the intraclass correlation coefficient to quantify how much of the difference in ECMO inpatient costs was associated with the hospital where a child received care. To do this, we adjusted for patient factors, hospital factors and potentially modifiable factors such as complications, procedures and length of stay.Results:The median inflation-adjusted inpatient costs for children requiring ECMO were $183,000, $240,000 and $241,000 in years 2006, 2009 and 2012, respectively. The largest median cost for ECMO cases in a given hospital in a given year ($690,000) was more than 11 times that of the smallest median cost ($60,000). After case-mix adjustment, 27% of the variation in inpatient costs was associated with the hospital where ECMO care was provided. Average hospital costs were not associated with hospital ECMO volume.Conclusions:The large variation in ECMO inpatient costs between hospitals suggests great variation in care between hospitals, which is important because hospitals have a co-existing variation in ECMO survival rates.

ObjectivesThe objective of this study was to associate ventilation rates during in-hospital cardiopulmonary resuscitation with 1) arterial blood pressure during cardiopulmonary resuscitation and 2) survival outcomes.DesignProspective, multicenter observational study.SettingPediatric and pediatric cardiac ICUs of the Collaborative Pediatric Critical Care Research Network.PatientsIntubated children (≥ 37 wk gestation and < 19 yr old) who received at least 1 minute of cardiopulmonary resuscitation.InterventionsNone.Measurements and main resultsArterial blood pressure and ventilation rate (breaths/min) were manually extracted from arterial line and capnogram waveforms. Guideline rate was defined as 10 ± 2 breaths/min; high ventilation rate as greater than or equal to 30 breaths/min in children less than 1 year old, and greater than or equal to 25 breaths/min in older children. The primary outcome was survival to hospital discharge. Regression models using Firth penalized likelihood assessed the association between ventilation rates and outcomes. Ventilation rates were available for 52 events (47 patients). More than half of patients (30/47; 64%) were less than 1 year old. Eighteen patients (38%) survived to discharge. Median event-level average ventilation rate was 29.8 breaths/min (interquartile range, 23.8-35.7). No event-level average ventilation rate was within guidelines; 30 events (58%) had high ventilation rates. The only significant association between ventilation rate and arterial blood pressure occurred in children 1 year old or older and was present for systolic blood pressure only (-17.8 mm Hg/10 breaths/min; 95% CI, -27.6 to -8.1; p < 0.01). High ventilation rates were associated with a higher odds of survival to discharge (odds ratio, 4.73; p = 0.029). This association was stable after individually controlling for location (adjusted odds ratio, 5.97; p = 0.022), initial rhythm (adjusted odds ratio, 3.87; p = 0.066), and time of day (adjusted odds ratio, 4.12; p = 0.049).ConclusionsIn this multicenter cohort, ventilation rates exceeding guidelines were common. Among the range of rates delivered, higher rates were associated with improved survival to hospital discharge.

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.

Aim Diastolic blood pressure (DBP) during cardiopulmonary resuscitation (CPR) is associated with survival following pediatric in-hospital cardiac arrest. The relationship between intra-arrest haemodynamics and neurological status among survivors of pediatric cardiac arrest is unknown. Methods This study represents analysis of data from the prospective multicenter Pediatric Intensive Care Quality of cardiopulmonary resuscitation (PICqCPR) Study. Primary predictor variables were median DBP and median systolic blood pressure (SBP) over the first 10 min of CPR. The primary outcome measure was “new substantive morbidity” determined by Functional Status Scale (FSS) and defined as an increase in the FSS of at least 3 points or increase of 2 in a single FSS domain. Univariable analyses were completed to investigate the relationship between new substantive morbidity and BPs during CPR. Results 244 index CPR events occurred during the study period, 77 (32%) CPR events met all inclusion criteria as well as having both DBP and FSS data available. Among 77 survivors, 32 (42%) had new substantive morbidity as measured by the FSS score. No significant differences were identified in DBP (median 30.5 mmHg vs. 30.9 mmHg, p = 0.5) or SBP (median 76.3 mmHg vs. 63.0 mmHg, p = 0.2) between patients with and without new substantive morbidity. Children who developed new substantive morbidity were more likely to have lower pre-arrest FSS than those that did not (median [IQR]: 7.5 [6.0–9.0] versus 9.0 [7.0–13.0], p = 0.01). Conclusion New substantive morbidity determined by FSS after a pediatric IHCA was associated with baseline functional status, but not DBP during CPR.

OBJECTIVES To describe survival and 3-month and 12-month neurobehavioral outcomes in children with preexisting neurobehavioral impairment enrolled in one of two parallel randomized clinical trials of targeted temperature management. DESIGN Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital and Out-of-Hospital trials data. SETTING Forty-one PICUs in the United States, Canada, and United Kingdom. PATIENTS Eighty-four participants (59 in-hospital cardiac arrest and 25 out-of-hospital cardiac arrest), 49 males, 35 females, mean age 4.6 years (SD, 5.36 yr), with precardiac arrest neurobehavioral impairment (Vineland Adaptive Behavior Scales, Second Edition composite score < 70). All required chest compressions for greater than or equal to 2 minutes, were comatose and required mechanical ventilation after return of circulation. INTERVENTIONS Neurobehavioral function was assessed using the Vineland Adaptive Behavior Scales, Second Edition at baseline (reflecting precardiac arrest status), and at 3 and 12 months postcardiac arrest, followed by on-site cognitive evaluation. Vineland Adaptive Behavior Scales, Second Edition norms are 100 (mean) ± 15 (SD); higher scores indicate better function. Analyses evaluated survival, changes in Vineland Adaptive Behavior Scales, Second Edition, and cognitive functioning. MEASUREMENTS AND MAIN RESULTS Twenty-eight of 84 (33%) survived to 12 months (in-hospital cardiac arrest, 19/59 (32%); out-of-hospital cardiac arrest, 9/25 [36%]). In-hospital cardiac arrest (but not out-of-hospital cardiac arrest) survival rate was significantly lower compared with the Therapeutic Hypothermia after Pediatric Cardiac Arrest group without precardiac arrest neurobehavioral impairment. Twenty-five survived with decrease in Vineland Adaptive Behavior Scales, Second Edition less than or equal to 15 (in-hospital cardiac arrest, 18/59 (31%); out-of-hospital cardiac arrest, 7/25 [28%]). At 3-months postcardiac arrest, mean Vineland Adaptive Behavior Scales, Second Edition scores declined significantly (-5; SD, 14; p < 0.05). At 12 months, Vineland Adaptive Behavior Scales, Second Edition declined after out-of-hospital cardiac arrest (-10; SD, 12; p < 0.05), but not in-hospital cardiac arrest (0; SD, 15); 43% (12/28) had unchanged or improved scores. CONCLUSIONS This study demonstrates the feasibility, utility, and challenge of including this population in clinical neuroprotection trials. In children with preexisting neurobehavioral impairment, one-third survived to 12 months and their neurobehavioral outcomes varied broadly.

To develop a prognostic model for predicting mortality at time of extracorporeal membrane oxygenation initiation for children which is important for determining center-specific risk-adjusted outcomes.Multivariable logistic regression using a large national cohort of pediatric extracorporeal membrane oxygenation patients.The ICUs of the eight tertiary care children's hospitals of the Collaborative Pediatric Critical Care Research Network.Five-hundred fourteen children (19 yr old), enrolled with an initial extracorporeal membrane oxygenation run for any indication between January 2012 and September 2014.None.A total of 514 first extracorporeal membrane oxygenation runs were analyzed with an overall mortality of 45% (n = 232). Weighted logistic regression was used for model selection and internal validation was performed using cross validation. The variables included in the Pediatric Extracorporeal Membrane Oxygenation Prediction model were age (pre-term neonate, full-term neonate, infant, child, and adolescent), indication for extracorporeal membrane oxygenation (extracorporeal cardiopulmonary resuscitation, cardiac, or respiratory), meconium aspiration, congenital diaphragmatic hernia, documented blood stream infection, arterial blood pH, partial thromboplastin time, and international normalized ratio. The highest risk of mortality was associated with the presence of a documented blood stream infection (odds ratio, 5.26; CI, 1.90-14.57) followed by extracorporeal cardiopulmonary resuscitation (odds ratio, 4.36; CI, 2.23-8.51). The C-statistic was 0.75 (95% CI, 0.70-0.80).The Pediatric Extracorporeal Membrane Oxygenation Prediction model represents a model for predicting in-hospital mortality among children receiving extracorporeal membrane oxygenation support for any indication. Consequently, it holds promise as the first comprehensive pediatric extracorporeal membrane oxygenation risk stratification model which is important for benchmarking extracorporeal membrane oxygenation outcomes across many centers.

To inform design aspects of future trials by comparing 3 and 12-month neurobehavioural outcomes in children enrolled in Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-Of-Hospital and In-Hospital (THAPCA-OH, THAPCA-IH) trials.The THAPCA trials evaluated two targeted temperature management interventions (hypothermia, 32.0-34.0 °C; normothermia, 36.0-37.5 °C). Children, aged 2 days to18 years, were enrolled from 2009-2015. Three and 12-month post-cardiac arrest (CA) outcomes included the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) (population mean = 100, SD = 15) and the pediatric cerebral performance category (PCPC) scale. Children without significant pre-existing neurodevelopmental deficits were included in primary outcome analyses. Among survivors, favorable 12-month outcome was defined as VABS-II ≥ 70.VABS-II and PCPC were available at 3 and 12 months in 204 of 222 eligible survivors (THAPCA-OH, n = 82; THAPCA-IH, n = 122). Relative to THAPCA-IH, THAPCA-OH had significantly less pre-CA disability and significantly greater 12-month CA impairment, based on both VABS-II and PCPC. Correlations between 3 and 12-month VABS-II scores were strong for THAPCA-OH (r = 0.95) and THAPCA-IH (r = 0.72), and lower (p ≤ 0.001) in THAPCA-IH. Between time-points correlations were lower, but still significant in children1 year at CA (p 0.001). In both cohorts, 3-month VABS-II and PCPC categorical outcomes had high sensitivity (≥70%) for predicting favorable 12-month VABS-II outcomes, but specificity was lower for THAPCA-IH (68-89%) relative to THAPCA-OH (≥95%). Overall, 12-month diagnostic accuracy was ≥80% for both VABS-II and PCPC in both cohorts.In future paediatric cardiac arrest clinical trials that enroll similar cohorts, integration of 3-month neurobehavioral outcome measures should be considered.

To explore the safety and efficacy of targeted temperature management amongst infants with out-of-hospital cardiac arrest due to an apparent life threatening event (ALTE) recruited to the Therapeutic Hypothermia after Paediatric Cardiac Arrest Out-of-Hospital trial.Fifty-four infants (48h to1year of age) with ALTE who received chest compressions for ≥2min, were comatose, and required mechanical ventilation after return of circulation were included. Infants were randomised to therapeutic hypothermia (33°C) (n=26) or therapeutic normothermia (36.8°C) (n=28) within six hours of return of circulation. Outcomes included 12-month survival with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score ≥70, 12-month survival, change in VABS-II score from pre-arrest to 12 months post-arrest, and select safety measures.Amongst infants with pre-arrest VABS-II ≥70 (n=52), there was no difference in 12-month survival with VABS-II ≥70 between therapeutic hypothermia and therapeutic normothermia groups (2/25 (8.0%) vs. 1/27 (3.7%); relative risk 2.16; 95% confidence interval 0.21-22.38, p=0.60). Amongst all evaluable infants (n=53), the change in VABS-II score from pre-arrest to 12 months post-arrest did not differ (p=0.078) between therapeutic hypothermia and therapeutic normothermia groups, nor did 12-month survival (5/26 (19.2%) vs. 1/27 (3.7%); relative risk 5.19; 95% confidence interval 0.65-41.50, p=0.10).Mortality was high amongst infants that were comatose after out-of-hospital cardiac arrest due to ALTE in both therapeutic hypothermia and therapeutic normothermia treated groups. Functional status was markedly reduced among survivors. (ClinicalTrials.gov, NCT00878644).

To investigate relationships between cardiac arrest characteristics and survival and neurobehavioral outcome among children recruited to the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial.Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial data.Thirty-six PICUs in the United States and Canada.All children (n = 295) had chest compressions for greater than or equal to 2 minutes, were comatose, and required mechanical ventilation after return of circulation.Neurobehavioral function was assessed using the Vineland Adaptive Behavior Scales, Second Edition at baseline (reflecting prearrest status) and 12 months postarrest. U.S. norms for Vineland Adaptive Behavior Scales, Second Edition scores are 100 (mean) ± 15 (SD). Higher scores indicate better functioning. Outcomes included 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70.Cardiac etiology of arrest, initial arrest rhythm of ventricular fibrillation/tachycardia, shorter duration of chest compressions, compressions not required at hospital arrival, fewer epinephrine doses, and witnessed arrest were associated with greater 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. Weekend arrest was associated with lower 12-month survival. Body habitus was associated with 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70; underweight children had better outcomes, and obese children had worse outcomes. On multivariate analysis, acute life threatening event/sudden unexpected infant death, chest compressions more than 30 minutes, and weekend arrest were associated with lower 12-month survival; witnessed arrest was associated with greater 12-month survival. Acute life threatening event/sudden unexpected infant death, other respiratory causes of arrest except drowning, other/unknown causes of arrest, and compressions more than 30 minutes were associated with lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70.Many factors are associated with survival and neurobehavioral outcome among children who are comatose and require mechanical ventilation after out-of-hospital cardiac arrest. These factors may be useful for identifying children at risk for poor outcomes, and for improving prevention and resuscitation strategies.

OBJECTIVES To describe family burden among caregivers of children who survived out-of-hospital cardiac arrest and who were at high risk for neurologic disability and examine relationships between family burden, child functioning, and other factors during the first year post arrest. DESIGN Secondary analysis of data from the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial. SETTING Thirty-six PICUs in the United States and Canada. PATIENTS Seventy-seven children recruited to the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial who had normal prearrest neurologic functioning and were alive 1 year post arrest. INTERVENTIONS Family burden was assessed using the Infant Toddler Quality of Life Questionnaire for children less than 5 years old and the Child Health Questionnaire for children 5 years old or older at baseline (reflecting prearrest status), 3 months, and 12 months post arrest. Child functioning was assessed using the Vineland Adaptive Behavior Scale II, the Pediatric Overall Performance Category, and Pediatric Cerebral Performance Category scales and caregiver perception of global functioning. MEASUREMENTS AND MAIN RESULTS Fifty-six children (72.7%) were boys, 48 (62.3%) were whites, and 50 (64.9%) were less than 5 years old prior to out-of-hospital cardiac arrest. Family burden at baseline was not significantly different from reference values. Family burden was increased at 3 and 12 months post arrest compared with reference values (p < 0.001). Worse Pediatric Overall Performance Category and Pediatric Cerebral Performance Category, lower adaptive behavior, lower global functioning, and higher family burden all measured 3 months post arrest were associated with higher family burden 12 months post arrest (p < 0.05). Sociodemographics and prearrest child functioning were not associated with family burden 12 months post arrest. CONCLUSIONS Families of children who survive out-of-hospital cardiac arrest and have high risk for neurologic disability often experience substantial burden during the first year post arrest. The extent of child dysfunction 3 months post arrest is associated with family burden at 12 months.

Objectives:To determine the incidence of cardiopulmonary resuscitation in PICUs and subsequent outcomes.Design, Setting, and Patients:Multicenter prospective observational study of children younger than 18 years old randomly selected and intensively followed from PICU admission to hospital discharge

Introduction: Based on laboratory CPR investigations and limited adult data, the American Heart Association Consensus Statement on CPR Quality recommends titrating end-tidal carbon dioxide (ETCO2) to > 20 mmHg during CPR. Hypothesis: ETCO2 > 20 mmHg during pediatric in-hospital CPR is associated with survival to hospital discharge. Methods: Children > 37 weeks gestation in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for > 1 minute and ETCO2 monitoring prior to and during CPR between July 1, 2013 and June 31, 2016 were included. ETCO2 and Utstein-style cardiac arrest data were collected. Multivariable Poisson regression models with robust error estimates were used to estimate relative risk of outcomes. Results: Investigators blinded to outcome analyzed ETCO2 waveforms from 43 children for the first (up to) 10 minutes of CPR. During CPR, the median ETCO2 was 23 mmHg (quartiles, 16 and 28 mmHg), median ventilation rate was 29 breaths/minute (quartiles, 24 and 35 bpm), and median duration of CPR was 5 minutes [quartiles, 2 and 16 minutes]. Return of spontaneous circulation occurred after 71% of CPR events and 37% of patients survived to hospital discharge. For children with mean ETCO2 during CPR > 20 mmHg, the adjusted relative risk for return of spontaneous circulation was 1.32 (0.89, 1.95), p= 0.16 and for survival to hospital discharge was 0.92 (0.41, 2.08), p= 0.84. Further sensitivity analyses were unable to demonstrate an association between mean ETCO2 > 25 mmHg or > 30 mmHg and ROSC or survival to hospital discharge. The median mean ETCO2 among children who survived to hospital discharge was 20 mmHg [quartiles; 15, 28 mmHg] versus 23 mmHg [16, 28 mmHg] among non-survivors. Conclusion: Mean ETCO2 > 20 mmHg during pediatric in-hospital CPR was not associated with ROSC or survival to hospital discharge. ETCO2 was not demonstrably different among survivors versus non-survivors.

Background Based on laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data, the American Heart Association Consensus Statement on CPR Quality recommends titrating CPR performance to achieve end-tidal carbon dioxide (ETCO2) >20 mmHg. Aims We prospectively evaluated whether ETCO2 > 20 mmHg during CPR was associated with survival to hospital discharge. Methods Children ≥37 weeks gestation in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for ≥1 min and ETCO2 monitoring prior to and during CPR between July 1, 2013 and June 31, 2016 were included. ETCO2 and Utstein-style cardiac arrest data were collected. Multivariable Poisson regression models with robust error estimates were used to estimate relative risk of outcomes. Results Blinded investigators analyzed ETCO2 waveforms from 43 children. During CPR, the median ETCO2 was 23 mmHg [quartiles, 16 and 28 mmHg], median ventilation rate was 29 breaths/min [quartiles, 24 and 35 breaths/min], and median duration of CPR was 5 min [quartiles, 2 and 16 min]. Return of spontaneous circulation occurred after 71% of CPR events and 37% of patients survived to hospital discharge. For children with mean ETCO2 during CPR > 20 mmHg, the adjusted relative risk for survival was 0.92 (0.41, 2.08), p = 0.84. The median mean ETCO2 among children who survived to hospital discharge was 20 mmHg [quartiles; 15, 28 mmHg] versus 23 mmHg [16, 28 mmHg] among non-survivors. Conclusion Mean ETCO2 > 20 mmHg during pediatric in-hospital CPR was not associated with survival to hospital discharge, and ETCO2 was not different in survivors versus non-survivors.

Background: On the basis of laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data demonstrating that survival depends on attaining adequate arterial diastolic blood pressure (DBP) during CPR, the American Heart Association recommends using blood pressure to guide pediatric CPR. However, evidence-based blood pressure targets during pediatric CPR remain an important knowledge gap for CPR guidelines. Methods: All children ≥37 weeks’ gestation and Results: Blinded investigators analyzed blood pressure waveforms during CPR from 164 children, including 60% P =0.007) and survival with favorable neurological outcome (adjusted relative risk, 1.6; 95% confidence interval, 1.1–2.5; P =0.02). Conclusions: These data demonstrate that mean DBP ≥25 mm Hg during CPR in infants and ≥30 mm Hg in children ≥1 year old was associated with greater likelihood of survival to hospital discharge and survival with favorable neurological outcome.

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 minutes, 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. 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

Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality.Prospective cohort study from December 4, 2011, to April 7, 2013.General and cardiac/cardiovascular PICUs at seven sites.Randomly selected PICU patients from their first PICU admission.None.Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%). Morbidity and mortality were significantly (p0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios.New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.

BackgroundTherapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.MethodsWe conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest.ResultsA total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality.ConclusionsIn comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

ObjectiveTo implement a standardized approach to characterize neurologic outcomes among 12-month survivors in the Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) trials.MethodsTwo 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.ResultsNeurologic 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.ConclusionThe 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.

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 minutes, were comatose, and required mechanical ventilation after return of circulation were included. Neurobehavioural function was assessed using the Vineland Adaptive Behaviour Scale, 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 to

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest.Retrospective analysis of a public access dataset.Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network.Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004.None.Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury.This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Extracorporeal membrane oxygenation (ECMO) is used for respiratory and cardiac failure in children but is complicated by bleeding and thrombosis.(1) To measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support; (2) to identify factors associated with these complications; and (3) to determine the impact of these complications on patient outcome.This was a prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals, carried out from December 2012 to September 2014.ECMO was used on 514 consecutive patients under age 19 years. Demographics, anticoagulation practices, severity of illness, circuitry components, bleeding, thrombotic events, and outcome were recorded. Survival was 54.9%. Bleeding occurred in 70.2%, including intracranial hemorrhage in 16%, and was independently associated with higher daily risk of mortality. Circuit component changes were required in 31.1%, and patient-related clots occurred in 12.8%. Laboratory sampling contributed to transfusion requirement in 56.6%, and was the sole reason for at least one transfusion in 42.2% of patients. Pump type was not associated with bleeding, thrombosis, hemolysis, or mortality. Hemolysis was predictive of subsequent thrombotic events. Neither hemolysis nor thrombotic events increased the risk of mortality.The incidences of bleeding and thrombosis are high during ECMO support. Laboratory sampling is a major contributor to transfusion during ECMO. Strategies to reduce the daily risk of bleeding and thrombosis, and different thresholds for transfusion, may be appropriate subjects of future trials to improve outcomes of children requiring this supportive therapy.

To understand factors affecting nurses' attitudes toward the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials and association with approach/consent rates.Cross-sectional survey of pediatric/cardiac intensive care nurses' perceptions of the trials.Study was conducted at 16 of 38 self-selected study sites.Pediatric and cardiac intensive care nurses.The primary outcome was the proportion of nurses with positive perceptions, as defined by agree or strongly agree with the statement "I am happy to take care of a Therapeutic Hypothermia after Pediatric Cardiac Arrest patient". Associations between perceptions and study approach/consent rates were also explored. Of 2,241 nurses invited, 1,387 (62%) completed the survey and 77% reported positive perceptions of the trials. Nurses, who felt positively about the scientific question, the study team, and training received, were more likely to have positive perceptions of the trials (p0.001). Nurses who had previously cared for a research patient had significantly more positive perceptions of Therapeutic Hypothermia After Pediatric Cardiac Arrest compared with those who had not (79% vs 54%; p0.001). Of the 754 nurses who cared for a Therapeutic Hypothermia After Pediatric Cardiac Arrest patient, 82% had positive perceptions, despite 86% reporting it required more work. Sixty-nine percent believed that hypothermia reduces brain injury and mortality; sites had lower consent rates when their nurses believed that hypothermia was beneficial. Institution-specific approach rates were positively correlated with nurses' perceptions of institutional support for the trial (r = 0.54; p = 0.04), ICU support (r = 0.61; p = 0.02), and the importance of conducting the trial in children (r = 0.61; p = 0.01).The majority of nurses had positive perceptions of the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials. Institutional, colleague, and study team support and training were contributing factors. Despite increased work, nurses remained enthusiastic demonstrating that studies with intensive bedside nursing procedures are feasible. Institutions whose nurses believed hypothermia was beneficial had lower consent rates, suggesting that educating nurses on study rationale and equipoise may enhance study participation.

Objective To describe the association of systolic hypotension during the first 6 hours after successful resuscitation from pediatric cardiopulmonary arrest (CA) with in-hospital mortality.

Objectives To assess the association of diastolic blood pressure cutoffs (≥ 25 mm Hg in infants and ≥ 30 mm Hg in children) during cardiopulmonary resuscitation with return of spontaneous circulation and survival in surgical cardiac versus medical cardiac patients. Secondarily, we assessed whether these diastolic blood pressure targets were feasible to achieve and associated with outcome in physiology unique to congenital heart disease (single ventricle infants, open chest), and influenced outcomes when extracorporeal cardiopulmonary resuscitation was deployed. Design Multicenter, prospective, observational cohort analysis. Setting Tertiary PICU and cardiac ICUs within the Collaborative Pediatric Critical Care Research Network. Patients Patients with invasive arterial catheters during cardiopulmonary resuscitation and surgical cardiac or medical cardiac illness category. Interventions None. Measurements and main results Hemodynamic waveforms during cardiopulmonary resuscitation were analyzed on 113 patients, 88 surgical cardiac and 25 medical cardiac. A similar percent of surgical cardiac (51/88; 58%) and medical cardiac (17/25; 68%) patients reached the diastolic blood pressure targets (p = 0.488). Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients (p = 0.018), but not medical cardiac patients (p = 0.359). Fifty-three percent (16/30) of patients with single ventricles attained the target diastolic blood pressure. In patients with an open chest at the start of chest compressions, 11 of 20 (55%) attained the target diastolic blood pressure. In the 33 extracorporeal cardiopulmonary resuscitation patients, 16 patients (48%) met the diastolic blood pressure target with no difference between survivors and nonsurvivors (p = 0.296). Conclusions During resuscitation in an ICU, with invasive monitoring in place, diastolic blood pressure targets of greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in children can be achieved in patients with both surgical and medical heart disease. Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients, but not medical cardiac patients. Diastolic blood pressure targets were feasible to achieve in 1) single ventricle patients, 2) open chest physiology, and 3) extracorporeal cardiopulmonary resuscitation patients.

To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials.Multicenter randomized controlled trials.Pediatric intensive care and cardiac ICUs in the United States and Canada.Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent.Therapeutic hypothermia or therapeutic normothermia.From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015.Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

Objective Determine if the shortest sampling interval for laboratory variables used to estimate baseline severity of illness in pediatric critical care is equivalently sensitive across multiple sites without site-specific bias, while accounting for the vast majority of dysfunction compared to the standard 0 hour to 12 hour Pediatric Risk of Mortality (PRISM) III score.

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.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).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 (p0.001), 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.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.

To analyze functional performance measures collected prospectively during the conduct of a clinical trial that enrolled children (up to age 18 yr old), resuscitated after out-of-hospital cardiac arrest, who were at high risk of poor outcomes.Children with Glasgow Motor Scale score less than 5, within 6 hours of resuscitation, were enrolled in a clinical trial that compared two targeted temperature management interventions (THAPCA-OH, NCT00878644). The primary outcome, 12-month survival with Vineland Adaptive Behavior Scale, second edition, score greater or equal to 70, did not differ between groups.Thirty-eight North American PICUs.Two hundred ninety-five children were enrolled; 270 of 295 had baseline Vineland Adaptive Behavior Scale, second edition, scores greater or equal to 70; 87 of 270 survived 1 year.Targeted temperatures were 33.0°C and 36.8°C for hypothermia and normothermia groups.Baseline measures included Vineland Adaptive Behavior Scale, second edition, Pediatric Cerebral Performance Category, and Pediatric Overall Performance Category. Pediatric Cerebral Performance Category and Pediatric Overall Performance Category were rescored at hospital discharges; all three were scored at 3 and 12 months. In survivors with baseline Vineland Adaptive Behavior Scale, second edition scores greater or equal to 70, we evaluated relationships of hospital discharge Pediatric Cerebral Performance Category with 3- and 12-month scores and between 3- and 12-month Vineland Adaptive Behavior Scale, second edition, scores. Hospital discharge Pediatric Cerebral Performance Category scores strongly predicted 3- and 12-month Pediatric Cerebral Performance Category (r = 0.82 and 0.79; p0.0001) and Vineland Adaptive Behavior Scale, second edition, scores (r = -0.81 and -0.77; p0.0001). Three-month Vineland Adaptive Behavior Scale, second edition, scores strongly predicted 12-month performance (r = 0.95; p0.0001). Hypothermia treatment did not alter these relationships.In comatose children, with Glasgow Motor Scale score less than 5 in the initial hours after out-of-hospital cardiac arrest resuscitation, function scores at hospital discharge and at 3 months predicted 12-month performance well in the majority of survivors.

OBJECTIVE: To describe outcomes and complications in the drowning subgroup from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial. DESIGN: Exploratory post hoc cohort analysis. SETTING: Twenty-four PICUs. PATIENTS: Pediatric drowning cases. INTERVENTIONS: Therapeutic hypothermia versus therapeutic normothermia. MEASUREMENTS AND MAIN RESULTS: An exploratory study of pediatric drowning from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial was conducted. Comatose patients aged more than 2 days and less than 18 years were randomized up to 6 hours following return-of-circulation to hypothermia (n = 46) or normothermia (n = 28). Outcomes assessed included 12-month survival with a Vineland Adaptive Behavior Scale score of greater than or equal to 70, 1-year survival rate, change in Vineland Adaptive Behavior Scale-II score from prearrest to 12 months, and select safety measures. Seventy-four drowning cases were randomized. In patients with prearrest Vineland Adaptive Behavior Scale-II greater than or equal to 70 (n = 65), there was no difference in 12-month survival with Vineland Adaptive Behavior Scale-II score of greater than or equal to 70 between hypothermia and normothermia groups (29% vs 17%; relative risk, 1.74; 95% CI, 0.61-4.95; p = 0.27). Among all evaluable patients (n = 68), the Vineland Adaptive Behavior Scale-II score change from baseline to 12 months did not differ (p = 0.46), and 1-year survival was similar (49% hypothermia vs 42%, normothermia; relative risk, 1.16; 95% CI, 0.68-1.99; p = 0.58). Hypothermia was associated with a higher prevalence of positive bacterial culture (any blood, urine, or respiratory sample; 67% vs 43%; p = 0.04); however, the rate per 100 days at risk did not differ (11.1 vs 8.4; p = 0.46). Cumulative incidence of blood product use, serious arrhythmias, and 28-day mortality were not different. Among patients with cardiopulmonary resuscitation durations more than 30 minutes or epinephrine doses greater than 4, none had favorable Pediatric Cerebral Performance Category outcomes (≤ 3). CONCLUSIONS: In comatose survivors of out-of-hospital pediatric cardiac arrest due to drowning, hypothermia did not result in a statistically significant benefit in survival with good functional outcome or mortality at 1 year, as compared with normothermia. High risk of culture-proven bacterial infection was observed in both groups. Language: en