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OBJECTIVE Neonatal cardiac surgery with cardiopulmonary bypass is often complicated by morbidity associated with inflammation and low cardiac output syndrome. Hydrocortisone "stress dosing" is reported to provide hemodynamic benefits in some patients with refractory shock. Development of cardiopulmonary bypass-induced adrenal insufficiency may provide further rationale for postoperative hydrocortisone administration. We sought to determine whether prophylactic, postoperative hydrocortisone infusion could decrease prevalence of low cardiac output syndrome after neonatal cardiac surgery with cardiopulmonary bypass. DESIGN Double-blind, randomized control trial. SETTING Pediatric cardiac ICU and operating room in tertiary care center. PATIENTS Forty neonates undergoing cardiac surgery with cardiopulmonary bypass were randomized (19 hydrocortisone and 21 placebo). Demographics and known risk factors were similar between groups. INTERVENTIONS After cardiopulmonary bypass separation, bolus hydrocortisone (50 mg/m²) or placebo was administered, followed by continuous hydrocortisone infusion (50 mg/m²/d) or placebo tapered over 5 days. Adrenocorticotropic hormone stimulation testing (1 μg) was performed before and after cardiopulmonary bypass, prior to steroid administration. Blood was collected for cytokine analysis before and after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS Subjects receiving hydrocortisone were less likely to develop low cardiac output syndrome (5/19, 26% vs 12/21, 57%; p = 0.049). Hydrocortisone group had more negative net fluid balance at 48 hours (-114 vs -64 mL/kg; p = 0.01) and greater urine output at 0-24 hours (2.7 vs 1.2 mL/kg/hr; p = 0.03). Hydrocortisone group weaned off catecholamines and vasopressin sooner than placebo, with a difference in inotrope-free subjects apparent after 48 hours (p = 0.033). Five placebo subjects (24%) compared with no hydrocortisone subjects required rescue steroids (p = 0.02). Thirteen (32.5%) had adrenal insufficiency after cardiopulmonary bypass. Patients with adrenal insufficiency randomized to receive hydrocortisone had lower prevalence of low cardiac output syndrome compared with patients with adrenal insufficiency randomized to placebo (1/6 vs 6/7, respectively; p = 0.02). Hydrocortisone significantly reduced proinflammatory cytokines. Ventilator-free days, hospital length of stay, and kidney injury were similar. CONCLUSIONS 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.

Superior vena cava oxygen saturation monitoring in the early postoperative period after the Norwood procedure (NP) has been associated with improved survival and decreased adverse events (AE). There is no data describing inferior vena cava saturation (Sivo2) monitoring after NP. We sought to investigate the utility of intermittent Sivo2 monitoring after NP and to assess the correlation of Sivo2 with renal near-infrared spectroscopy (rNIRS). We hypothesized failure to achieve Sivo2 greater than 45% within the first 4 hours after NP is predictive of AE, and that rNIRS correlates with Sivo2.A retrospective study of 26 consecutive NP patients who received postoperative management with Sivo2 monitoring according to a strict protocol was conducted. Primary outcome was AE, defined as cardiopulmonary resuscitation, extracorporeal membrane oxygenation, death before discharge, or residual surgical defects.Ten (38%) patients had one or more AE; mortality was 23%. On admission to the cardiac intensive care unit, patients with AE had lower Sivo2 (45% ± 9.4% versus 62% ± 12.0%; p0.001) and lower rNIRS (56 ± 6.5 versus 77 ± 7.2; p0.001). At 4 hours, 90% of AE patients had an Sivo2 less than 45% versus 6% of non-AE patients. Both Sivo2 and rNIRS were highly predictive of AE: the area under the receiver-operating characteristic curve was greater than 0.86 and 0.95, respectively. Two hours after admission, an Sivo2 less than 45% predicted AE with a specificity of 93%, a sensitivity of 70%, and a positive predictive value of 82%. The Sivo2 was strongly correlated with rNIRS (r = 0.81).Intermittent Sivo2 can be used to guide early postoperative NP management; rNIRS is an accurate continuous, noninvasive surrogate for Sivo2. An Sivo2 of less than 45% in the first 4 hours after the NP is predictive of AE.

Background: We sought to determine whether immediate postoperative serum cortisol concentration predicts adrenal insufficiency in neonates after cardiac surgery with cardiopulmonary bypass. We hypothesized that cortisol 2 − Svo2] 28% vs 32%, P = .05) were both lower among patients with levels of cortisol 2 − Svo2 ( P < .001), maximum inotrope score ( P = .014), initial 24-hour fluid intake ( P = .012), and time to negative fluid balance ( P = .008) and was negatively correlated with initial 24-hour urine output ( P < .001). Conclusions: 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.

Despite significant progress in the understanding and treatment of sepsis, it continues to be a major health problem in United States and around the world. Sepsis accounted for nearly 4,500 deaths (mortality rate 10%) and approximately $2 billion per year in healthcare expenditures in the U.S. alone. In this review, we will revisit the definitions of pediatric sepsis and discuss the epidemiology of sepsis in the United States. During inflammatory states, the vascular endothelium plays a crucial role in modulating the host immune response and regulates the levels of coagulation, pro-inflammatory and anti-inflammatory factors in the blood. We review the role of endothelium in nitric oxide generation and activation of the coagulation cascade. Studies in critically ill patients and animal models have shown that increased apoptosis or “programmed cell death” of lymphoid organs contributes to immune suppression, anergy, and organ system dysfunction. In this chapter, we outline both intrinsic and extrinsic pathways that lead to apoptosis.

High mobility group box chromosomal protein 1 (HMGB1) is a DNA-binding protein that exhibits proinflammatory 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 hours before exposure to LTA (10 μg/mL) decreased secretion of tumor necrosis factor, nuclear factor-κB DNA-binding, and degradation of IκBα. Denaturation of HMGB1 with boiling water or coincubation with anti-HMGB1 antibody abrogated the induction of tolerance to LTA. In contrast, coincubation 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 lipopolysaccharide contamination. Bone marrow-derived macrophages obtained from C57Bl/6 wild-type and RAGE-deficient mice became LTA-tolerant after 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.

BackgroundHypogammaglobulinemia 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 their course after cardiopulmonary bypass (CPB), and determine if post-CPB hypogammaglobulinemia was associated with increased morbidity.MethodsThis was a single-center, retrospective analysis of infants who underwent cardiac surgery with CPB between June 2010 and December 2011. The Ig concentration was obtained from banked plasma of 47 patients from a prior study (pre-CPB, immediately post-CPB, and 24 and 48 hours post-CPB). In addition, any Ig levels drawn for clinical purposes after CPB were included. Ig levels were excluded if drawn after chylothorax diagnosis or intravenous IgG administration.ResultsThe median age was 7 days. Preoperative Ig concentration was similar to that described in healthy children. IgG level decreased to less than 50% of preoperative concentration by 24-hour post-CPB and failed to recover by 7 days. Of 47 patients, 25 (53%) had low IgG (