Sedation Management for Critically Ill Children with Pre-Existing Cognitive Impairment.

OBJECTIVE: To compare current analgesia and sedation management practices between critically ill children with pre-existing cognitive impairment and critically ill neurotypical children, including possible indicators of therapeutic efficacy. STUDY DESIGN: This study used secondary analysis of prospective data from the RESTORE clinical trial, with 2449 children admitted to the pediatric intensive care unit and receiving mechanical ventilation for acute respiratory failure. Subjects with a baseline Pediatric Cerebral Performance Category ≥3 were defined as subjects with cognitive impairment, and differences between groups were explored using regression methods accounting for pediatric intensive care unit as a cluster variable. RESULTS: This study identified 412 subjects (17%) with cognitive impairment. Compared with neurotypical subjects, subjects with cognitive impairment were older (median, years, 6.2 vs 1.4; P < .001) with more severe pediatric acute respiratory distress syndrome (40% vs 33%; P = .009). They received significantly lower cumulative doses of opioids (median, mg/kg, 14.2 vs 16.2; P < .001) and benzodiazepines (10.6 vs 14.4; P < .001). Three nonverbal subjects with cognitive impairment received no analgesia or sedation. Subjects with cognitive impairment were assessed as having more study days awake and calm and fewer study days with an episode of pain. They were less likely to be assessed as having inadequate pain/sedation management or unplanned endotracheal/invasive tube removal. Subjects with cognitive impairment had more documented iatrogenic withdrawal symptoms than neurotypical subjects. CONCLUSIONS: Subjects with cognitive impairment in this study received less medication, but it is unclear whether they have authentically lower analgesic and/or sedative requirements or are vulnerable to inadequate assessment of discomfort because of the lack of validated assessment tools. We recommend the development of pain and sedation assessment tools specific to this patient population.

White Matter Volume Predicts Language Development in Congenital Heart Disease.

OBJECTIVE: To determine whether brain volume is reduced at 1 year of age and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. STUDY DESIGN: Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II and the MacArthur-Bates Communicative Development Inventories at 1 year of age. A multitemplate based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the group with CHD, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. RESULTS: Compared with controls, infants with CHD had reductions of 54 mL in total brain (P = .009), 40 mL in cerebral white matter (P <.001), and 1.2 mL in brainstem (P = .003) volumes. Within the group with CHD, brain volumes were not correlated with Bayley Scales of Infant Development-II scores but did correlate positively with MacArthur-Bates Communicative Development Inventory language development. CONCLUSIONS: Infants with biventricular CHD show total brain volume reductions at 1 year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00006183.

Accuracy of an Extubation Readiness Test in Predicting Successful Extubation in Children With Acute Respiratory Failure From Lower Respiratory Tract Disease.

OBJECTIVE: Identifying children ready for extubation is desirable to minimize morbidity and mortality associated with prolonged mechanical ventilation and extubation failure. We determined the accuracy of an extubation readiness test (Randomized Evaluation of Sedation Titration for Respiratory Failure extubation readiness test) in predicting successful extubation in children with acute respiratory failure from lower respiratory tract disease. DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial, a pediatric multicenter cluster randomized trial of sedation. SETTING: Seventeen PICUs in the intervention arm. PATIENTS: Children 2 weeks to 17 years receiving invasive mechanical ventilation for lower respiratory tract disease. INTERVENTION: Extubation readiness test in which spontaneously breathing children with oxygenation index less than or equal to 6 were placed on FIO2 of 0.50, positive end-expiratory pressure of 5 cm H2O, and pressure support. MEASUREMENTS AND MAIN RESULTS: Of 1,042 children, 444 (43%) passed their first extubation readiness test. Of these, 295 (66%) were extubated within 10 hours of starting the extubation readiness test, including 272 who were successfully extubated, for a positive predictive value of 92%. Among 861 children who were extubated for the first time within 10 hours of performing an extubation readiness test, 788 passed their extubation readiness test and 736 were successfully extubated for a positive predictive value of 93%. The median time of day for extubation with an extubation readiness test was 12:15 hours compared with 14:54 hours for extubation without an extubation readiness test within 10 hours (p < 0.001). CONCLUSIONS: In children with acute respiratory failure from lower respiratory tract disease, an extubation readiness test, as described, should be considered at least daily if the oxygenation index is less than or equal to 6. If the child passes the extubation readiness test, there is a high likelihood of successful extubation.

Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial.

OBJECTIVE: To assess the association of postoperative tight glycemic control and hypoglycemia in children undergoing cardiac surgery with neurodevelopmental outcomes at 1 year of age. STUDY DESIGN: A 2-center, prospective, randomized trial of postoperative tight glycemic control vs standard care was conducted in 980 children undergoing cardiac surgery. Neurodevelopmental outcomes were assessed at nine to 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Adaptive Behavior Assessment System, Second Edition, the Ages and Stages Questionnaire, Third Edition, and the Brief Infant Toddler Social-Emotional Assessment. RESULTS: Neurodevelopmental follow-up was performed on 237 patients with a mean age of 13 months. No significant treatment group differences were found in the Bayley-III and Adaptive Behavior Assessment System, Second Edition composite scores or percentage at risk based on the Ages and Stages Questionnaire, Third Edition and the Brief Infant Toddler Social-Emotional Assessment. Patients who experienced moderate to severe hypoglycemia (n = 8) had lower Bayley-III composite scores compared with patients with no to mild hypoglycemia, even after controlling for factors known to be associated with poorer neurodevelopmental outcomes. CONCLUSION: For infants undergoing cardiac surgery, tight glycemic control did not impact neurodevelopmental outcomes compared with standard care. These data suggest a possible association between moderate to severe hypoglycemia and poorer neurodevelopmental outcomes at 1 year of age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00443599.

Altered Gray Matter in Adolescents with d-Transposition of the Great Arteries.

OBJECTIVE: To investigate the structural brain characteristics of adolescent patients with d-transposition of the great arteries (d-TGA), repaired with the arterial switch operation in early infancy, using quantitative volumetric magnetic resonance imaging. STUDY DESIGN: Ninety-two patients with d-TGA from the Boston Circulatory Arrest Study (76% male; median age at scan 16.1 years) and 49 control subjects (41% male; median age at scan 15.7 years) were scanned using a 1.5-Tesla magnetic resonance imaging system. Subcortical and cortical gyral volumes and cortical gyral thicknesses were measured using surface-based morphometry. Group differences were assessed with linear regression. RESULTS: Compared with controls, patients with d-TGA demonstrated significantly reduced subcortical volumes bilaterally in the striatum and pallidum. Cortical regions that showed significant volume and thickness differences between groups were distributed throughout parietal, medial frontoparietal, cingulate, and temporal gyri. Among adolescents with d-TGA, volumes and thicknesses correlated with several perioperative variables, including age at surgery, cooling duration, total support time, and days in the cardiac intensive care unit. CONCLUSIONS: Adolescents with d-TGA repaired early in life exhibit widespread differences from control adolescents in gray matter volumes and thicknesses, particularly in parietal, midline, and subcortical brain regions, corresponding to white matter regions already known to demonstrate altered microstructure. These findings complement observations made in white matter in this group and suggest that the adolescent d-TGA cognitive profile derives from altered brain development involving both white and gray matter.

White matter microstructure and cognition in adolescents with congenital heart disease.

OBJECTIVE: To describe the relationship between altered white matter microstructure and neurodevelopment in children with dextro-transposition of the great arteries (d-TGA). STUDY DESIGN: We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n = 49) and controls (n = 29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. RESULTS: Among the patients with d-TGA, mathematics achievement correlated with left parietal FA (r = 0.39; P = .006), inattention/hyperactivity symptoms correlated with right precentral FA (r = -0.39; P = .006) and left parietal FA (r = -0.30; P = .04), executive function correlated with right precentral FA (r = -0.30; P = .04), and visual-spatial skills correlated with right frontal FA (r = 0.30; P = .04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA (r = 0.29; P = .047). CONCLUSION: Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to that seen in healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy.