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Background: Excessive hemorrhage is a major complication after cardiac surgery requiring cardiopulmonary bypass (CPB). The aim of this study was to define the potential role of the cone and platelet analyzer (CPA) and the rotating thromboelastogram (ROTEM) point of care tests in children undergoing CPB., Procedure: We prospectively studied 15 pediatric patients aged 1 month to 10 years. Blood count, blood coagulation tests (prothrombin time [PT], activated partial thromboplastin time, fibrinogen, thrombin time), CPA and ROTEM parameters were measured before and after CPB. Demographic and surgical data were recorded as were those on perioperative blood loss and blood product transfusion., Results: Low body weight, longer duration on CPB and lower core body temperature were associated with an increased bleeding risk. The ROTEM test showed a significant prolongation of clotting time and decreased maximal clot firmness (MCF) postoperatively in children with increased bleeding. The coagulation parameters associated with increased bleeding were: prolonged PT, lower fibrinogen levels, prior to surgery, and lower MCF after surgery. CPA test findings were not associated with postoperative bleeding in our patients., Conclusions: CPA did not serve as a prognostic tool for predicting bleeding risk in children undergoing CPB. The change in ROTEM's post-CPB results associated with bleeding tendency, and they may predict for poorer clot formation and stability., (Copyright © 2010 Wiley-Liss, Inc.)

Purpose: Leptin and interleukin-6 (IL-6) are inversely correlated and associated with decreased survival in critically ill patients. We investigated changes in leptin, IL-6, and troponin in children undergoing open-heart surgery, hypothesizing that IL-6 and troponin will increase after cardiopulmonary bypass (CPB) and will be negatively correlated with leptin., Patients and Methods: Serial blood samples were collected from 21 patients 24 hours before and up to 48 hours after surgery., Results: Leptin levels decreased by 50% during CPB (P < .001), then gradually increased, reaching baseline levels 12 hours after surgery. The IL-6 levels increased (P < .001) during CPB, peaking 2 hours after surgery and remaining slightly elevated at 24 hours after surgery (P < .001). Leptin and IL-6 were negatively correlated (R = -0.448, P < .001). Troponin levels increased during CPB (P < .001). Postoperative leptin and troponin were inversely correlated (r = -0.535, P < .001). Patients with modest elevations in troponin levels (<20 microg/L) had a shorter aortic clamp and CPB time (P < .01), lower IL-6 peak levels (P = .03), and shorter duration of ventilation and inotropic support compared with patients with peak troponin levels greater than 20 microg/L., Conclusions: Lower leptin and higher IL-6 levels correlated with troponin, a marker of myocardial injury. Because leptin may have cardioprotective effects, the postoperative drop in its levels may further contribute to myocardial dysfunction.

This 10-year Medline search of English-language articles describing experimental and clinical studies on chemokines, cardiopulmonary bypass (CPB) and systemic or multiorgan failure revealed that chemokines are significantly involved in the pathogenesis of post-CPB syndrome. The post-CPB inflammatory response depends upon recruitment and activation of inflammatory cells. Leucocyte recruitment is a well-orchestrated process that involves several protein families, including pro-inflammatory cytokines, adhesion molecules and chemokines. Current anti-inflammatory therapies mostly act on the cells that have already been recruited. A more efficient therapy might be the prevention of excessive recruitment of particular leucocyte populations by antagonizing chemokine receptors which might act upstream of the current anti-inflammatory agents. The chemokines, which are a cytokine subfamily of chemotactic cytokines, participate in recognizing, recruiting, removing and repairing inflammation. As chemokines target specific leucocyte subsets, antagonism of a single chemokine ligand or receptor would be expected to have a circumscribed effect, thereby endowing the antagonist with a limited side-effect profile. Chemokines should be considered as possible targets for therapeutic intervention.

Objective: This study was undertaken to determine the relationship between plasma tumor necrosis factor concentrations and hemodynamic and metabolic parameters during the postoperative clinical course in children undergoing cardiac surgery., Methods: Tumor necrosis factor levels of 10 consecutive children undergoing surgery for repair of congenital heart defects were analyzed in blood samples drawn at predetermined time points during surgery and up to 24 hours thereafter. Clinical data were collected at these times for correlation to tumor necrosis factor levels., Results: All the patients survived. Tumor necrosis factor was detected in all 10 children. Tumor necrosis factor levels declined after induction of general anesthesia (201 +/- 65 pg/mL) steadily decreasing during surgery, reaching 80 +/- 50 pg/mL at 24 hours after the operation. Tumor necrosis factor levels were found to be inversely correlated with mean blood pressure values and indicators of acidosis (bicarbonate levels and base excess, P <.03). They were not correlated with the durations of cardiopulmonary bypass and aortic crossclamping., Conclusions: Tumor necrosis factor released into the circulation during and after pediatric cardiac surgery under cardiopulmonary bypass may be related to the hemodynamic and acid-base changes observed after cardiac surgery. Elucidation of the relationship between tumor necrosis factor and patient outcome in high-risk patients awaits further studies.

Background: There is increasing evidence that cytokine-inducible leukocyte-endothelial adhesion molecules are instrumental in the postoperative inflammatory response following cardiopulmonary bypass (CPB). L-selectin was shown to be one of those neutrophil-endothelial cell adhesion molecules. This study aimed to investigate the relationship of the soluble adhesion molecule, sL-selectin, and the postoperative course in children undergoing CPB., Material/methods: To determine the time course of sL-selectin after CPB, serial blood samples of 9 children undergoing CPB were collected from the arterial line or from the bypass circuits preoperatively, on initiation of CPB and 1, 6, 12, 18, 24, and 48 hours postoperatively. Plasma was recovered immediately, aliquoted and frozen at -70 degrees C until use. Circulating sL-selectin molecules were measured with a sandwich enzyme-linked immunoabsorbent assay (ELISA) technique. There were significant changes in plasma levels of sL-selectin in patients following CPB, and these levels were associated with patient characteristics, operative variables and postoperative course. Low values of sL-selectin significantly correlated with inotropic support, low PRISM score, postoperative hypotension and fever. There was a significant association between the development of postoperative sepsis and low sL-selectin levels. No correlation was found between sL-selectin values and lactate concentration or neutrophil count., Conclusions: Our results suggest a relation between CPB-induced mediators and both early and late clinical effects. Although the mechanism for the changes of sL-selectin remains undetermined, the down-regulation of sL-selectin indicates neutrophil activation and supports the possibility that anti-adhesion therapies might participate in the prevention and treatment of the inflammatory response associated with CPB.

Background: Interleukin (IL)-8, an 8 kDa peptide, is the first chemoattractant identified as being specific for neutrophils. Its possible association with early postoperative morbidity following cardiopulmonary bypass (CPB) in infants and children is unknown. This prospective cohort study sought possible roles of IL-8 in the inflammatory response to CPB and investigated if changes in IL-8 levels and clinical course and outcome were related., Methods: IL-8 levels were measured in 16 children undergoing CPB. Systemic blood was collected after induction of anaesthesia (baseline), at 15 min after CPB onset and cessation, and at 1, 4, 8, 12 and 24 h thereafter., Results: Correlation coefficients between IL-8 levels and CPB time ranged from 0.45 to 0.55, heart rate 0.41--0.44, surgical time 0.41--0.63 and pH --0.56 to --0.50 (P < 0.05 for all parameters). Univariate analyses showed that patients requiring inotropic support and those with tachycardia had significantly higher postoperative IL-8 levels (P < 0.05). Furthermore, IL-8 levels were significantly higher in patients with surgical times > 200 min and in patients with an aortic clamp in place for > 65 min., Conclusions: There was an association between IL-8 and early postoperative heart rate, and the need for inotropic support IL-8 correlated positively with surgical time, CPB time and heart rate and negatively with pH. IL-8 release may be related to some of the haemodynamic changes in the early postoperative course following CPB. The relationship between IL-8 and late markers of patient outcome in high-risk infants awaits further studies.

This study aimed to examine the association between lactate levels in the first hours after surgery for congenital heart defects and the results of Risk-Adjusted Classification for Congenital Heart Surgery (RACHS-1) scoring and to evaluate serial lactate levels over time to determine whether they can serve as a supplementary tool for postoperative assessment within the same RACHS-1 group of patients. A retrospective cohort study was performed using data retrieved from a clinical database of 255 children who had surgery for congenital heart defects between 1999 and 2001 at Sheba Medical Center. Lactate levels were measured postoperatively four times (mg/dL units). The last sample was taken at the end of the surgical procedure, and lactate levels were measured at admission to the pediatrics critical care unit, then 6 and 12 h after admission. The lactate level was measured via arterial blood gases. A total of 27 deaths occurred, yielding a mortality rate of 7.4% when Norwood operations were excluded and 10.16% when they were included. The mean initial postoperative lactate level was significantly lower for survivors (42.2 ± 32.0 mg/dL) than for nonsurvivors (85.4 ± 54.1 mg/dL) ( p < 0.01). The serial mean lactate levels decreased progressively for all surviving patients ( r = 0.96) compared with nonsurvivors ( r = 0.02). The lactate levels correlated with the RACHS-1 subgroups at each time point ( r > 0.96 for all). The Pearson correlations between postoperative lactate levels (last lactate measurement taken in the operating room) and cardiopulmonary bypass (CPB) duration ( r = 0.549), clamp duration ( r = 0.586), and the inotropic score ( r = 0.466) ( p < 0.001 for all) were significantly positive. The correlations between the maximum lactate levels (during the first 12 postoperative hours) and CPB duration ( r = 0.496), clamp duration ( r = 0.509), and the inotropic score ( r = 0.633) ( p < 0.001 for all) were extremely positive. The early elevation of lactate levels in RACHS-1 subgroups 1 to 3 were highly correlated with poor prognosis and death ( p < 0.03). In addition, the lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. The survivors in RACHS-1 subgroups 1 to 3 had lower mean lactate levels than the nonsurvivors in this group ( P = 0.011), and this also held true for the survivors and nonsurvivors in RACHS-1 subgroups 4 to 6 ( P = 0.026). Lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. This combination allows the targeting of appropriately intensive interventions and therapies toward the sickest patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Fractalkine (FKN), a unique chemokine associated with pulmonary hypertension, may be involved in the acute stress response that regulates inflammation after cardiopulmonary bypass (CPB) surgery. We characterized FKN levels and correlated them with clinical parameters in children undergoing cardiac surgery involving CPB. Methods: Twenty-seven consecutive patients, aged 30days to 11.5years, who underwent surgery for correction of congenital heart defects, were prospectively studied. Serial blood samples were collected preoperatively, upon termination of CPB, and at six points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at −70°C until assayed. Clinical and laboratory data were collected. Results: Baseline FKN levels were skewed between patients. Patients with low FKN levels showed significantly higher levels of oxygen saturation in room air compared to patients with high FKN levels (p <0.05). Moreover, there was a positive correlation between preoperative pulmonary arterial hypertension and FKN levels (p <0.05). Surprisingly, FKN elevation from preoperative to postoperative levels displayed no discernible pattern. Conclusions: FKN levels significantly correlate with preoperative hypoxemia and PAH, suggesting that FKN may be up-regulated during hypoxemia. CPB is not associated with acute changes in circulating FKN levels. The role of FKN in the postoperative course should be further investigated. [Copyright &y& Elsevier]