Extracorporeal life support in pediatric cardiac dysfunction

<p>Abstract</p> <p>Background</p> <p>Low cardiac output (LCO) after corrective surgery remains a serious complication in pediatric congenital heart diseases (CHD). In the case of refractory LCO, extra corporeal life support (ECLS) extra corporeal membrane oxygenation (ECMO) or ventricle assist devices (VAD) is the final therapeutic option. In the present study we have reviewed the outcomes of pediatric patients after corrective surgery necessitating ECLS and compared outcomes with pediatric patients necessitating ECLS because of dilatated cardiomyopathy (DCM).</p> <p>Methods</p> <p>A retrospective single-centre cohort study was evaluated in pediatric patients, between 1991 and 2008, that required ECLS. A total of 48 patients received ECLS, of which 23 were male and 25 female. The indications for ECLS included CHD in 32 patients and DCM in 16 patients.</p> <p>Results</p> <p>The mean age was 1.2 ± 3.9 years for CHD patients and 10.4 ± 5.8 years for DCM patients. Twenty-six patients received ECMO and 22 patients received VAD. A total of 15 patients out of 48 survived, 8 were discharged after myocardial recovery and 7 were discharged after successful heart transplantation. The overall mortality in patients with extracorporeal life support was 68%.</p> <p>Conclusion</p> <p>Although the use of ECLS shows a significantly high mortality rate it remains the ultimate chance for children. For better results, ECLS should be initiated in the operating room or shortly thereafter. Bridge to heart transplantation should be considered if there is no improvement in cardiac function to avoid irreversible multiorgan failure (MFO).</p

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

BACKGROUND: Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-α production by monocytes. METHODOLOGY/PRINCIPAL FINDINGS: Pediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n = 38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes obtained pre-operatively for ex vivo LPS stimulations and TNF-α and IL-6 production was measured by flow cytometry. LPS-induced p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation by patient plasma was assessed by Western blotting. A cell-permeable peptide inhibitor was used to block STAT3 signaling. We found that plasma samples obtained 4 h after surgery, regardless of pre-operative dexamethasone treatment, potently inhibited LPS-induced TNF-α but not IL-6 synthesis by monocytes. This was not associated with attenuation of p38 MAPK activation or IκB-α degradation. However, abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-α production in the presence of suppressive patient plasma. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that STAT3 signaling plays a crucial role in the downregulation of TNF-α synthesis by human monocytes in the course of systemic inflammation in vivo. Thus, STAT3 might be a potential molecular target for pharmacological intervention in clinical syndromes characterized by systemic inflammation

Puerperal fever and neonatal pleural empyema and bacteremia caused by group A streptococcus

A term neonate developed early onset of sepsis and pleural empyema with group A streptococcus. Her mother also became septic with group A streptococcus in the early postpartum period. The infant required initial chest tube drainage. After reaccumulation of pleural fluid after removal of the chest tube, a thoracotomy with decortication was performed. The isolates of group A streptococcus were analyzed and found to be identical serotypes of the same bacterium. The serotyping revealed both to be M type 1, T pattern 1. Polymerase chain reaction detected the genomic sequence for streptococcal pyrogenic exotoxin A and B in both isolates. With the increase in invasive streptococcal infections in the community, serious perinatal infections may become more frequent

Preoperative and postoperative endotoxemia in children with congenital heart disease.

STUDY OBJECTIVES: Recent data indicate that increases in inflammatory cytokines are seen in patients with diverse cardiac diseases. However, the primary stimulus for cytokine secretion during cardiac illness remains unknown. Since bacterial endotoxin is a potent inducer of cytokines, we determined the incidence, magnitude, and clinical relevance of endotoxemia in children with congenital heart disease before and after surgical repair. DESIGN: A prospective, observational study. SETTING: A large, urban, university-affiliated, tertiary-care children\u27s hospital. PATIENTS: Thirty children with a variety of congenital heart defects (median age, 59 days; median weight, 4.0 kg) were sequentially enrolled. INTERVENTIONS: Blood was sampled prior to surgery, and at 1, 8, 24, 48, and 72 h following cardiopulmonary bypass. Assays included plasma endotoxin, lipopolysaccharide-binding protein (LBP), and interleukin-6 (IL-6). MEASUREMENTS AND RESULTS: Twenty-nine of 30 patients (96%) had evidence of endotoxemia during the study period. Twelve of the 30 patients (40%) were significantly endotoxemic prior to surgery. LBP, a plasma marker that responds to bacteria and endotoxin, rose significantly following cardiopulmonary bypass, as did the plasma levels of IL-6. Fifteen of 30 patients met prospectively defined criteria for experiencing a severe hemodynamic disturbance in their postoperative course. These patients had significantly higher preoperative plasma LBP (p \u3c 0.02) and plasma endotoxin levels (p \u3c 0.05), compared to patients with less-severely disturbed hemodynamics. Mortality was 25% in patients with preoperative endotoxemia, compared with no mortality in patients who were not endotoxemic before surgery (p = 0.05). CONCLUSIONS: These data demonstrate that endotoxemia in children with congenital heart disease is more common than previously suspected, and is associated with clinical outcomes. We conclude that clinical trials targeting endotoxin will be necessary to determine if endotoxin is a causal, etiologic agent in the disease process