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 .).

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.

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.

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.

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.).

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.

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.

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.

Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.

OBJECTIVES: The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development. DESIGN/SETTING: Consensus assessment of potential outcomes and evaluation timepoints. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Twelve months after arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in Vineland Adaptive Behavior Scales Second Edition from prearrest level, measured as quasicontinuous with death and vegetative status being worst-possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes because of easier interpretability and favored outcomes based solely on postarrest status because of concerns about accurate parental assessment of prearrest status and differing clinical impact of a given Vineland Adaptive Behavior Scales Second Edition change depending on prearrest status. Simulations found only modest power loss from categorizing or dichotomizing quasicontinuous outcomes because of high expected mortality. The primary outcome selected was survival with 12-month Vineland Adaptive Behavior Scales Second Edition no less than two SD below a reference population mean (70 points), necessarily evaluated only among children with prearrest Vineland Adaptive Behavior Scales Second Edition greater than or equal to 70. Two secondary efficacy outcomes, 12-month survival and quasicontinuous Vineland Adaptive Behavior Scales Second Edition change from prearrest level, will be evaluated among all randomized children, including those with compromised function prearrest. CONCLUSIONS: Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating prearrest status and using quasicontinuous versus simpler outcomes, was highly beneficial to the final Therapeutic Hypothermia After Pediatric Cardiac Arrest design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the potential disadvantages of primary outcome.

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

OBJECTIVE: To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. DESIGN: Multicenter randomized controlled trials. SETTING: Pediatric intensive care and cardiac ICUs in the United States and Canada. PATIENTS: 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. INTERVENTIONS: Therapeutic hypothermia or therapeutic normothermia. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Physical Abilities and Mobility Scale: reliability and validity in children receiving inpatient rehabilitation for acquired brain injury.

OBJECTIVE: To investigate the psychometric properties of the Physical Abilities and Mobility Scale (PAMS) in children receiving inpatient rehabilitation for acquired brain injury (ABI). DESIGN: Admission and discharge PAMS item and total scores were evaluated. The WeeFIM was used as the criterion standard. A case study was used to illustrate the complementary nature of the PAMS and WeeFIM. SETTING: A single, free-standing, academically affiliated pediatric rehabilitation hospital. PARTICIPANTS: Children (N=107) aged 2 through 18 years receiving inpatient rehabilitation for ABI between March 2009 and March 2012. Forty-two additional children treated during this time were excluded because of missing PAMS data. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Internal consistency was evaluated using Cronbach alpha. Interrater reliability was evaluated through overall agreement, Pearson correlations, and intraclass correlations. Construct validity was examined through exploratory factor analysis. Criterion validity was explored through correlations of PAMS overall and factor scores with WeeFIM total and subscale scores. Sensitivity to recovery was examined using paired t tests, examining differences between admission and discharge scores for each item and for the total score. RESULTS: Internal consistency and interrater reliability were high. Factor analysis revealed 2 factors: lower-level skills and higher-level mobility skills. Correlations with the WeeFIM ranged from moderate to very strong; total PAMS score most strongly correlated with the WeeFIM mobility subscore. Total PAMS score and each item score significantly increased between admission and discharge. CONCLUSIONS: The PAMS is a reliable and valid measure of progress during inpatient rehabilitation for children with ABI. By capturing fine-grain progress toward both lower-level and higher-level mobility skills, the PAMS complements the WeeFIM in assessing functional gains during the rehabilitation stay.

Examining acute rehabilitation outcomes for children with total functional dependence after traumatic brain injury: a pilot study.

OBJECTIVE: To examine in a pilot cohort factors associated with functional outcome at discharge and 3-month follow-up after discharge from inpatient rehabilitation in children with severe traumatic brain injury (TBI) who entered rehabilitation with the lowest level of functional skills. PARTICIPANTS: Thirty-nine children and adolescents (3-18 years old) who sustained a severe TBI and had the lowest possible rating at rehabilitation admission on the Functional Independence Measure for Children (total score = 18). METHODS: Retrospective review of data collected as part of routine clinical care. RESULTS: At discharge, 59% of the children were partially dependent for basic activities, while 41% remained dependent for basic activities. Initial Glasgow Coma Scale score, time to follow commands, and time from injury to rehabilitation admission were correlated with functional status at discharge. Time to follow commands and time from injury to rehabilitation admission were correlated with functional status at 3-month follow-up. Changes in functional status during the first few weeks of admission were associated with functional status at discharge and follow-up. CONCLUSIONS: Even children with the most severe brain injuries, who enter rehabilitation completely dependent for all daily activities, have the potential to make significant gains in functioning by discharge and in the following few months. Assessment of functional status early in the course of rehabilitation contributes to the ability to predict outcome from severe TBI.

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.

Interdisciplinary behavioral rehabilitation of pediatric pain-associated disability: retrospective review of an inpatient treatment protocol.

OBJECTIVE: A biopsychosocial model was used to treat pain-associated disability in children and adolescents. We assessed the clinical outcomes of children and adolescents (8-21 years of age) with pain-associated disability who were treated in an interdisciplinary inpatient rehabilitation program which included physical, occupational, and recreational therapy, medicine, nursing, pediatric psychology, neuropsychology, psychiatry, social work, and education. Psychological treatment emphasized cognitive-behavioral intervention for pain and anxiety management, and behavioral shaping to increase functioning. METHODS: We conducted a retrospective chart review of 41 consecutive patients. School attendance, sleep, and medication usage were assessed at admission and discharge; functional disability and physical mobility were assessed at admission, discharge, and 3-month follow-up. RESULTS: As a group, significant improvements were observed in school status, sleep, functional ability, physical mobility, and medication usage. CONCLUSION: Findings support the efficacy of an inpatient interdisciplinary behavioral rehabilitation approach to the treatment of pain-associated disability in pediatric patients.

Disruptive behaviour disorders and disruptive symptoms after severe paediatric traumatic brain injury.

OBJECTIVE: To determine pre-injury prevalence and post-injury incidence of DSM-III-R oppositional defiant disorder (ODD) and conduct disorder (CD), increase in disruptive symptoms after severe paediatric traumatic brain injury (TBI) and risk factors associated with development of these disturbances. METHODS: Ninety-four children were followed 1 one year after severe TBI. Assessments of pre-injury and 1-year psychiatric status were ascertained by parent report. The 1-year incidence of disruptive behaviour disorders/symptoms was the main outcome measure. RESULTS: The pre-injury prevalence of ODD and CD in the TBI sample was 6% and 8%, respectively, the prevalence of pre-injury CD being significantly higher than in a reference population. The incidence of new-onset ODD and CD 1-year post-injury was 9% and 8%, respectively, the incidence of new-onset CD being significantly higher than in a reference population. ODD symptoms and total number of disruptive symptoms increased significantly over the first post-injury year. Significant risk factors for disruptive disorders/symptoms included higher pre-injury psychosocial adversity, delinquency ratings and affective lability. CONCLUSIONS: Pre-injury conduct disorder is a significant risk factor for post-injury disruptive behaviours. New-onset CD and disruptive symptoms are consequences of TBI at 1-year post-injury. Risk factors for these post-injury disturbances are similar to risk factors in non-TBI populations.

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.

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.

Intensive care unit variables and outcome after pediatric traumatic brain injury: a retrospective study of survivors.

OBJECTIVE: Traumatic brain injury is a leading cause of death and disability in children. Hypotension has been associated with poor survival and outcome in children after traumatic brain injury, but the effect of acute hypertension is less certain. The objective was to obtain acute physiologic variables during the early hospitalization period in a cohort of children prospectively enrolled in another study. DESIGN: Retrospective chart reviews. SETTING: University-affiliated pediatric rehabilitation center. PATIENTS: Fifty-seven survivors, 5-17 yrs of age, admitted for rehabilitation between 1992 and 1995 after sustaining a traumatic brain injury. INTERVENTIONS: Standard of care. MEASUREMENTS AND MAIN RESULTS: Outcomes were assessed at 1 yr postinjury through cognitive testing of the child and parent interview of the child's global functional skills. Cognitive outcome was measured using the Performance IQ from the Wechsler Intelligence Scale for Children, Third Edition. Overall functional outcome was assessed using the Disability Rating Scale. CONCLUSIONS: This study suggests that early markers of secondary injury after moderate to severe traumatic brain injury in children may be predictive of long-term outcome. This study reinforces the need for longer term, systematic, and more precise measurements of outcomes in children with traumatic brain injury and prospective studies to examine the predictive value of acute management variables on multiple types of outcomes after traumatic brain injury in children.

Prevalence of aggressive behaviour after severe paediatric traumatic brain injury.

OBJECTIVE: The goals of this study were to explore the prevalence of aggressive behaviours after severe paediatric traumatic brain injury (TBI) and identify predictors of aggressive behaviours 1 year post-injury. METHODS: A cohort of 97 children aged 4-19 years at time of severe TBI (GCS 3-8) were prospectively followed for 1 year. Pre-injury psychiatric status was obtained retrospectively at enrolment and post-injury behavioural and functional concerns were assessed at 1 year. Aggression was measured with a modified version of the Overt Aggression Scale (OAS). RESULTS: Results revealed aggressive behaviour increased from pre-injury to post-injury. Pre-injury factors including aggression, attention problems and anxiety were associated with increased post-injury aggressive behaviour. Children with greater disability after injury were also at increased risk for aggressive behaviours. CONCLUSIONS: Aggression is a prevalent symptom after paediatric TBI and can significantly impede rehabilitation. Awareness of these predictors can aid in early identification of children at risk in order to help appropriately design rehabilitation programmes.

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.