Prophylactic, postoperative hydrocortisone reduces low cardiac output syndrome, improves fluid balance and urine output, and attenuates inflammation after neonatal cardiopulmonary bypass surgery. Further studies are necessary to show if these benefits lead to improvements in more important clinical outcomes.

Low cortisol obtained in the immediate postoperative period is not associated with worse postoperative outcomes or predictive of steroid responsiveness. In contrast, elevated levels of cortisol are positively correlated with severity of illness. The use of an absolute cortisol threshold to identify adrenal insufficiency and/or guide steroid therapy in neonates after cardiac surgery is unjustified.

High mobility group box chromosomal protein 1 (HMGB1) is a DNA binding protein that exhibits pro-inflammatory properties when present in the extracellular compartment. Putative receptors for HMGB1 include Toll-like receptor (TLR) 4, TLR2 and the receptor for advanced glycation end products (RAGE). We tested the hypothesis that extracellular HMGB1 can induce tolerance to the bacterial product, lipoteichoic acid (LTA). Pretreatment of human monocyte-like THP-1 cells with 1 μg/ml HMGB1 18 h before exposure to LTA (10 μg/ml) decreased secretion of TNF, NF-κB DNAbinding, and degradation of IκBα. Denaturation of HMGB1 with boiling water or co-incubation with anti-HMGB1 antibody abrogated the induction of tolerance to LTA. In contrast, co-incubation with polymyxin B failed to diminish HMGB1-induced tolerance to LTA. These findings support the view that the induction of LTA tolerance by HMGB1 was not due to LPS contamination. Bone marrowderived macrophages obtained from C57Bl/6 wild-type and RAGE-deficient mice became LTAtolerant following HMGB1 exposure ex vivo. We were unable to demonstrate LTA tolerance in TLR2 and TLR4-deficient macrophages, as they are hyporesponsive to LTA. These findings suggest that extracellular HMGB1 induces LTA tolerance, and RAGE receptor is not required for this induction.

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Background Hypogammaglobulinemia has been reported after cardiac surgery and may be associated with adverse outcomes. We sought to define baseline immunoglobulin (Ig) concentration in neonates and infants with congenital heart disease, determine its course following cardiopulmonary bypass (CPB), and determine if post-CPB hypogammaglobulinemia was associated with increased morbidity. Methods Single center, retrospective analysis of infants who underwent cardiac surgery with CPB between June 2010 and December 2011. Ig concentration obtained from banked plasma of 47 patients from a prior study (pre-CPB, immediately post-CPB, and 24- and 48-hours post-CPB). Additionally, any Ig levels drawn for clinical purposes after CPB were included. Ig levels were excluded if drawn after chylothorax diagnosis or intravenous immunoglobulin G administration. Results Median age was 7 days. Preoperative Ig concentration was similar to that described in healthy children. IgG level fell to less than 50% of preoperative concentration by 24-hr post-CPB and failed to recover by 7 days. 25/47 (53%) patients had low IgG after CPB (<248 mg/dl). Despite no difference in demographics or risk factors between patients with low and normal IgG, low IgG patients had more positive fluid balance at 24-hours, increased pro-inflammatory plasma cytokine levels, duration of mechanical ventilation, and CICU length of stay. Additionally, low IgG patients had increased incidence of post-operative infections (40% vs. 14%, p=0.056). Conclusions Hypogammaglobulinemia occurs in half of infants after CPB. Its association with fluid overload and increased inflammatory cytokines suggests it may result from capillary leak. Postoperative hypogammaglobulinemia is associated with increased morbidity, including more secondary infections.