Acute kidney injury after in-hospital cardiac arrest.

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 < 0.001). 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.

Methods Used to Maximize Follow-Up: Lessons Learned From the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials.

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.

Relationships between three and twelve month outcomes in children enrolled in the therapeutic hypothermia after pediatric cardiac arrest trials.

AIM: 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. METHODS: 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 to <18 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. RESULTS: 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 children <1 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. CONCLUSIONS: In future paediatric cardiac arrest clinical trials that enroll similar cohorts, integration of 3-month neurobehavioral outcome measures should be considered.

Cardiac Arrest Outcomes in Children With Preexisting Neurobehavioral Impairment.

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.

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.

One-Year Survival and Neurologic Outcomes After Pediatric Open-Chest Cardiopulmonary Resuscitation.

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.

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.

Neuropsychological Outcomes of Children 1 Year After Pediatric Cardiac Arrest: Secondary Analysis of 2 Randomized Clinical Trials.

Importance: Little is known about neuropsychological outcomes of children who survived pediatric cardiac arrest (CA). Objective: To describe the neuropsychological outcomes of CA survivors enrolled in the Therapeutic Hypothermia After Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) and Out-of-Hospital (THAPCA-OH) trials and compare the results with the primary outcome measure for these trials. Design, Setting, and Participants: Secondary analysis of 222 CA survivors aged 1 to 18 years who received chest compressions for 2 minutes or more, remained comatose and required mechanical ventilation after return of circulation, and were enrolled in targeted temperature-management trials from 41 pediatric intensive care units. Data were collected from September 3, 2009, to February 3, 2016, and analyzed from March 10, 2017, to April 20, 2018. Main Outcomes and Measures: The Vineland Adaptive Behavior Scales, Second Edition (VABS-II), a standardized measure of neurobehavioral functioning based on caregiver report (age-corrected mean [SD] scores = 100 [15]), was used to evaluate pre-CA functioning within 24 hours after enrollment; VABS-II<70 indicated significant developmental delays; VABS-II and neuropsychological testing were completed 1 year after CA. Neuropsychological testing included the Mullen Scales of Early Learning (Mullen) for children younger than 6 years and the Wechsler Abbreviated Scale of Intelligence (WASI) and neuropsychological measures of attention, memory, processing speed, and executive functioning for older children. Results: Of 160 participants who completed neuropsychological testing, 96 (60.0%) were male; the median (interquartile range [IQR]) age was 2.5 years (1.3-6.1 years). Ninety-six (60.0%) were white, 41 (25.6%) were black, and 23 (14.4%) were of other/unknown race; 343 (21.2%) were Hispanic or Latino; 119 (74.4%) were non-Hispanic or Latino; and 7 (4.4%) were of unknown ethnicity. One hundred fourteen participants (71.2%) were classified as having favorable outcomes (VABS-II ≥70). Impairments (>2 SD below the mean for age) across neuropsychological measures ranged from 7% to 61%. Correlations between global cognitive and VABS-II scores were strong for younger children (Mullen, r = 0.69-0.87) but moderate for older children (r = 0.21-0.54 for the WASI). Of 111 children with favorable outcomes on VABS-II, 25.2% had global cognitive impairment and 30 of 35 older children (85.7%) had selective neuropsychological deficits. Conclusions and Relevance: In this prospectively evaluated cohort of pediatric CA survivors who were initially comatose, although 71.2% were classified as having favorable outcomes, significant neuropsychological deficits were identified in pediatric CA survivors who were classified as having favorable outcomes. The findings provide clinicians with a greater understanding of the spectrum of neuropsychological outcomes of pediatric CA survivors and the complex relationship between standardized caregiver-reported functional outcome measures incorporated in clinical trials and performance-based neuropsychological assessments.

Acute kidney injury after out of hospital pediatric cardiac arrest.

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 h 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 < 0.001) and 12 months (21% vs no severe AKI 42%, p < 0.001). One year survival with favorable functional outcome was lower in those with severe AKI. CONCLUSIONS AND RELEVANCE: Severe AKI occurs frequently in children with ROSC after OHCA, especially in younger children and those with higher initial lactates and hemodynamic support. Severe AKI was associated with worse survival and functional outcome. Therapeutic hypothermia did not reduce the incidence of severe AKI.

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.

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.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours 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 score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Exploring the safety and efficacy of targeted temperature management amongst infants with out-of-hospital cardiac arrest due to apparent life threatening events.

OBJECTIVE: 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. METHODS: Fifty-four infants (48h to <1year 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. RESULTS: 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). CONCLUSIONS: 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).

Pediatric Out-of-Hospital Cardiac Arrest Characteristics and Their Association With Survival and Neurobehavioral Outcome.

OBJECTIVE: 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. DESIGN: Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial data. SETTING: Thirty-six PICUs in the United States and Canada. PATIENTS: 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. INTERVENTIONS: 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. MEASUREMENT AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Targeted Temperature Management After Pediatric Cardiac Arrest Due To Drowning: Outcomes and Complications.

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.

Family Burden After Out-of-Hospital Cardiac Arrest in Children.

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.

Neurobehavioral Outcomes in Children After Out-of-Hospital Cardiac Arrest.

OBJECTIVE: This study examined 12-month neurobehavioral outcomes in children who survived out-of-hospital cardiac arrest (OH-CA), were comatose after resuscitation, and were enrolled in a clinical trial to evaluate targeted temperature management to hypothermia (33.0°C) or normothermia (36.8°C) (Therapeutic Hypothermia after Pediatric Cardiac Arrest, Out-of-Hopsital [THAPCA-OH]; NCT00878644). METHODS: Baseline functioning was assessed by caregiver responses on the Vineland Adaptive Behavior Scales-Second Edition (VABS-II) soon after OH-CA (based on functioning before OH-CA); children with broadly normal baseline functioning (VABS-II ≥70) were included in the THAPCA-OH primary outcome. VABS-II was completed again 12 months later. Then, face-to-face cognitive evaluations were completed. Analyses evaluated changes in VABS-II composite, domain, and subdomain scores and cognitive functioning at follow-up. RESULTS: Ninety-six of 295 enrolled children were alive at 12 months; 87 of 96 had broadly normal baseline functioning (VABS-II ≥70). Follow-up was obtained on 85/87. Forty-two of 85 had VABS-II ≥70 at 12 months. VABS-II composite, domain, and subdomain scores declined significantly between baseline and 12-month follow-up (P < .001). Declines were greatest in older children. Most children displayed well below average cognitive functioning. Older age at cardiac arrest and higher baseline VABS-II scores were predictive of greater decline in neurobehavioral function. Treatment with hypothermia did not influence neurobehavioral outcomes. CONCLUSIONS: This is the largest study exploring long-term neurobehavioral outcomes in children surviving OH-CA who were comatose after resuscitation. Results revealed significant neurobehavioral morbidity across multiple functional domains, based both on caregiver reports and performance on objective cognitive measures, in survivors 1 year later.

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: In 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.).