Objective Children with congenital heart disease (CHD) have loss of intestinal epithelial barrier function (EBF), which increases their risk for post-operative sepsis and organ dysfunction. We do not understand how post-operative cardiopulmonary support or the inflammatory response to cardiopulmonary bypass (CPB) might alter intestinal EBF. We examined variation in a panel of plasma biomarkers to reflect intestinal EBF (cellular and paracellular structure and function) after CPB and in response to routine ICU care. Design Prospective cohort Setting University medical center cardiac intensive care unit Patients Twenty children aged newborn to 18 years undergoing repair or palliation of CHD with CPB. Interventions We measured baseline and repeated plasma FABP2, citrulline, claudin 3, and dual sugar permeability test (DSPT) to reflect intestinal epithelial integrity, epithelial function, paracellular integrity, and paracellular function, respectively. We measured baseline and repeated plasma pro-inflammatory (IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL4, IL10) cytokines, known to modulate intestinal EBF in murine models of CPB. Measurements and Main Results All patients had abnormal baseline FABP2 concentrations (mean 3815.5 pg/mL), (normal 41–336 pg/mL). Cytokine response to CPB was associated with early, but not late changes in plasma concentrations of FABP2 and citrulline. Variation in biomarker concentrations over time were associated with aspects of ICU care indicating greater severity of illness: claudin 3, FABP2, and DSPT ratio were associated with symptoms of feeding intolerance (p<0.05) while FABP2 was positively associated with vasoactive-inotrope score (VIS) (p=0.04). Citrulline was associated with larger arteriovenous O2 saturation difference (p=0.04) and had a complex relationship with VIS. Conclusions Children undergoing CPB for repair or palliation of CHD are at risk for intestinal injury and often present with evidence for loss of intestinal epithelial integrity pre-operatively. Greater severity of illness requiring increased cardiopulmonary support rather than the inflammatory response to CPB seems to mediate late post-operative intestinal EBF.

Objectives To understand factors affecting nurses' attitudes towards the Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) trials and association with approach/consent rates. Design, setting and participants Cross sectional survey of pediatric/cardiac intensive care nurses' perceptions of the trials, conducted at 16 of 38 self-selected study sites. Measurements The primary outcome was the proportion of nurses with positive perceptions, as defined by agree or strongly agree with the statement “I am happy to take care of a THAPCA patient”. Associations between perceptions and study approach/consent rates were also explored. Results Of 2241 nurses invited, 1387 (62%) completed the survey and 77% reported positive perceptions of the trials. Nurses, who felt positively about the scientific question, the study team, and training received, were more likely to have positive perceptions of the trials (p <0.001). Nurses who had previously cared for a research patient had significantly more positive perceptions of THAPCA compared with those who had not (79% vs. 54%, p<0.001). Of the 754 nurses who cared for a THAPCA patient, 82% had positive perceptions, despite 86% reporting it required more work. Sixty-nine percent believed that hypothermia reduces brain injury and mortality; sites had lower consent rates when their nurses believed that hypothermia was beneficial. Institution-specific approach rates were positively correlated with nurses' perceptions of institutional support for the trial (r=0.54, p=0.04), intensive care unit support (r=0.61, p=0.02), and the importance of conducting the trial in children (r=0.61, p=0.01). Conclusions The majority of nurses had positive perceptions of the THAPCA trials. Institutional, colleague and study team support and training were contributing factors. Despite increased work, nurses remained enthusiastic demonstrating that studies with intensive bedside nursing procedures are feasible. Institutions whose nurses believed hypothermia was beneficial had lower consent rates suggesting that educating nurses on study rationale and equipoise may enhance study participation.