Neuropsychological outcomes of children 1 year after pediatric cardiac arrest

Beth S. Slomine, Faye S. Silverstein, James R. Christensen, et al.  Neuropsychological Outcomes of Children 1 Year After Pediatric Cardiac Arrest.  JAMA Neurology.  Published online September 17, 2018. doi:10.1001/jamaneurol.2018.2628

Key Points

Question  How do caregiver-reported measures compare with performance-based measures in describing neuropsychological outcomes of children resuscitated after cardiac arrest who were initially comatose after return of circulation?

Findings  This secondary analysis of 2 clinical trials found that, of 160 survivors of pediatric cardiac arrest without significant developmental delay before cardiac arrest, 114 had favorable caregiver-rated outcomes 1 year later. However, significant performance-based neuropsychological deficits were evident across measures.

Meaning  These data provide clinicians with a greater understanding of neuropsychological outcomes in pediatric cardiac arrest survivors and of strong correlations in young children and moderate correlations in older children between caregiver-reported outcomes used in clinical trials and performance-based cognitive outcomes.

Abstract

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.
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Pediatric cardiac arrest survivors initially classified as having favorable outcomes had significant neuropsychological impairments when tested a year later, a prospective evaluation found.

While 71% of survivors in the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) and the Therapeutic Hypothermia After Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) clinical trials were rated as having favorable neurobehavioral outcomes by their caregivers, a secondary analysis showed many of these children had performance-based neuropsychological deficits, reported Beth Slomine, PhD, of the Kennedy Krieger Institute, and colleagues in JAMA Neurology. 

"The data collected for the THAPCA trials provide a unique opportunity to report on the largest sample of neurobehavioral and neuropsychological outcomes of prospectively recruited pediatric cardiac arrest survivors," Slomine told MedPage Today.

"These results provide clinicians with a better understanding of the range of outcomes in pediatric cardiac arrest survivors and provide researchers with a better understanding of the relationship between distinct outcomes assessment methods used in clinical trials."

THAPCA trials compared outcomes of two targeted temperature-management strategies (hypothermia at 33°C/91.4°F versus normothermia at 36.8°C/98.24°F) in children ages 2 days to 18 years who survived cardiac arrest and received chest compressions for 2 minutes or more, remained comatose, and required mechanical ventilation after circulation returned.

In both trials, hypothermia did not significantly improve 1-year survival with a favorable neurobehavioral outcome, which was defined as a score of 70 or greater (>2 SD below the mean for age) on the Vineland Adaptive Behavior Scales, second edition (VABS-II). The VABS-II assessment was based on telephone surveys with caregivers who reported daily functioning in multiple domains 1 year after cardiac arrest.

To complement VABS-II data collected 12 months after the arrest event, Slomine and co-authors conducted on-site neuropsychological testing with 160 THAPCA survivors, excluding children with severe impairment who lacked functional means of communication. For children under age 6 (n=119), they administered the Mullen Scales of Early Learning; for older children (n=41), they used the Wechsler Abbreviated Scale of Intelligence (WASI) and tests of processing speed, attention, learning and memory, executive functioning, and visuomotor functioning. 

Impairment across neuropsychological measures ranged from 7% to 61%. Correlations between VABS-II outcomes and global cognitive scores were strong for younger children (Mullen r=0.69-0.87), but moderate for older children (WASI r=0.21-0.54).

Test results showed global cognitive impairments in younger children and domain-specific impairments in older children. 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. Older children showed the highest impairment in measures of executive functioning, fine motor skill, visuomotor skills, and visual memory; IQ generally was spared.

This study is subject to several limitations, the authors noted. A minority of patients survived to 1 year after cardiac arrest (33.4% in THAPCA-OH and 47.4% in THAPCA-IH); brain death or withdrawal of life support due to poor neurologic prognosis was a frequent cause of death. Older children with severe hypoxic-ischemic brain injury were excluded from the study, so results underestimate impairment in this age group. Deficits may become more apparent as children mature, and neuropsychological functioning may need to be reassessed.

https://www.medpagetoday.com/neurology/generalneurology/75133