A Randomized Clinical Trial of Perfusion Modalities in Pediatric Congenital Heart Surgery Patients.

BACKGROUND: The objective of this randomized clinical trial was to investigate the effects of perfusion modalities on cerebral hemodynamics, vital organ injury, quantified by the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score, and clinical outcomes in risk-stratified congenital cardiac surgery patients. METHODS: This randomized clinical trial included 159 consecutive congenital cardiac surgery patients in whom pulsatile (n = 83) or nonpulsatile (n = 76) perfusion was used. Cerebral hemodynamics were assessed using transcranial Doppler ultrasound. Multiple organ injury was quantified using the PELOD-2 score at 24, 48, and 72 hours. Clinical outcomes, including intubation time, intensive care unit length of stay (LOS), hospital LOS, and mortality, were also evaluated. RESULTS: The Pulsatility Index at the middle cerebral artery and in the arterial line during aortic cross-clamping was consistently better maintained in the pulsatile group. Demographics and cardiopulmonary bypass characteristics were similar between the 2 groups. While risk stratification with The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Mortality Categories was similar between the groups, Mortality Categories 1 to 3 demonstrated more patients than Mortality Categories 4 and 5. There were no differences in clinical outcomes between the groups. The PELOD-2 scores showed a progressive improvement from 24 hours to 72 hours, but the results were not statistically different between the groups. CONCLUSIONS: The Pulsatillity Index for the pulsatile group demonstrated a more physiologic pattern compared with the nonpulsatile group. While pulsatile perfusion did not increase plasma-free hemoglobin levels or microemboli delivery, it also did not demonstrate any improvements in clinical outcomes or PELOD-2 scores, suggesting that while pulsatile perfusion is a safe method, it not a "magic bullet" for congenital cardiac operations.

MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.

Tracheal aspirate transcriptomic and miRNA signatures of extreme premature birth with bronchopulmonary dysplasia.

OBJECTIVE: Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with prematurity and BPD. STUDY DESIGN: We analyzed miRNA and mRNA profiles in tracheal aspirates (TAs) from 55 infants receiving invasive mechanical ventilation. Twenty-eight infants were extremely preterm and diagnosed with BPD, and 27 were term babies receiving invasive mechanical ventilation for elective procedures. RESULT: We found 22 miRNAs and 33 genes differentially expressed (FDR < 0.05) in TAs of extreme preterm infants with BPD vs. term babies without BPD. Pathway analysis showed associations with inflammatory response, cellular growth/proliferation, and tissue development. CONCLUSIONS: Specific mRNA-miRNA signatures in TAs may serve as biomarkers for BPD pathogenesis, a consequence of extreme prematurity.

Retrospective outcomes of glucose control in critically ill children.

BACKGROUND: Hyperglycemia is a significant problem for critically ill children. Treatment for hyperglycemia remains controversial. This study explores the effect of controlling blood glucose (BG) in hyperglycemic critically ill children. METHODS: A retrospective cohort of nondiabetic critically ill children (defined as requiring mechanical ventilation and/or vasopressors) with BG persistently ≥ 150 mg/dl and treated with insulin (treatment group) were compared with a historical cohort of similar children who did not receive interventions to control hyperglycemia (baseline group). RESULTS: There were 130 children in the treatment group and 137 children in the baseline group. Mean BG in the treatment group was 140 ± 24 mg/dl compared with 179 ± 47 mg/dl in the baseline group (p < .001). After adjusting for patient characteristics, cointerventions, and glucose metrics, patients in the treatment group had 2.5 fewer intensive care unit (ICU)-free days (i.e., number of days alive and discharged from ICU within 28 days after inclusion) than the baseline group (p = .023). Glucose control was not independently associated with duration of ICU stay, ventilator-free days, vasopressor-free days, or mortality. CONCLUSIONS: Blood glucose control appears associated with worse outcomes in critically ill children. Our data combined with conflicting results in adults leads us to strongly advocate for the conduct of randomized trials on glucose control in critically ill children.

Clinical outcomes of children receiving intensive cardiopulmonary support during hematopoietic stem cell transplant.

OBJECTIVE: We investigated the short-term and 1-year clinical outcomes of 129 children who received intensive cardiopulmonary support during hematopoietic stem cell transplant. Intensive cardiopulmonary support was defined as receiving at least one of the following interventions: continuous positive pressure ventilation, dopamine infusion greater than or equal to 10 mcg/kg/minute, or the use of any other vasoactive infusion. Duration of intensive cardiopulmonary support, survival to hospital discharge, and predictors of these outcome variables were compared with 387 hematopoietic stem cell transplant patients who did not receive intensive support during the same period. We also report the 1-year survival; presence of chronic graft-versus-host disease; and renal, cardiac, and pulmonary function for all patients. DESIGN: A multicenter retrospective cohort study. SETTING: The ICU and hematopoietic stem cell transplant unit of nine pediatric tertiary care centers. PATIENTS: Children undergoing hematopoietic stem cell transplant who required intensive cardiopulmonary support. INTERVENTIONS: None. RESULTS: Predictors of the need for intensive support included unrelated donor allogeneic transplant, glomerular filtration rate less than 85 mL/minute/1.73 m, and nonmalignant disease as the indication for transplant. The survival to discontinuation of intensive support for all patients was 62% and 58% for patients who received invasive mechanical ventilatory support. The duration of mechanical ventilation was not predictive of survival. Predictors of intensive support mortality included macroscopic bleeding, engraftment, and pediatric logistic organ dysfunction score greater than one in two domains. Survival to hospital discharge was 50% for the intensive support group and 99% for the nonintensive support group. Overall 1-year survival was 40% in the intensive support population and 65% in the nonintensive support group. There were no significant differences in the survival, rates of chronic graft-versus-host disease, creatinine, forced expiratory volume in 1-minute, cardiac shortening fraction, or performance status in intensive and nonintensive support patients who survived to hospital discharge. CONCLUSION: Intensive cardiopulmonary support plays an important and potentially life-saving role in the care of pediatric stem cell transplant patients. Survivors of intensive support do not have compromised 1-year survival or organ function compared with children who did not receive intensive support.

Assessment of parental presence during bedside pediatric intensive care unit rounds: effect on duration, teaching, and privacy.

OBJECTIVE: There is a paucity of literature evaluating the effects of family member presence during bedside medical rounds in the pediatric intensive care unit. We hypothesized that, when compared with rounds without family members, parental presence during morning medical rounds would increase time spent on rounds, decrease medical team teaching/education, increase staff dissatisfaction, create more stress in family members, and violate patient privacy in our open unit. DESIGN: Prospective, blinded, observational study. SETTING: Academic pediatric intensive care unit with 12 beds. PARTICIPANTS: A total of 105 admissions were studied, 81 family members completed a survey, and 187 medical team staff surveys were completed. INTERVENTIONS: Investigators documented parental presence and time allocated for presentation, teaching, and answering questions. Surveys related to perception of goals, teaching, and privacy of rounds were distributed to participants. MEASUREMENTS: Time spent on rounds, time spent teaching on rounds, and medical staff and family perception of the effects of parental presence on rounds. RESULTS: There was no significant difference between time spent on rounds in the presence or absence of family members (p = NS). There is no significant difference between the time spent teaching by the attending physician in the presence or absence of family members (p = NS). Overall, parents reported that the medical team spent an appropriate amount of time discussing their child and were not upset by this discussion. Parents did not perceive that their own or their child's privacy was violated during rounds. The majority of medical team members reported that the presence of family on rounds was beneficial. CONCLUSIONS: Parental presence on rounds does not seem to interfere with the educational and communication process. Parents report satisfaction with participation in rounds, and privacy violations do not seem to be a concern from their perspective.