Preoperative and postoperative endotoxemia in children with congenital heart disease

Study objectives: Recent data indicate that increases in inflammatory cytok ines are seen in patients with disease cardiac diseases. However, the prima ry stimulus for cytokine secretion during cardiac illness remains unknown. Since bacterial endotoxin is a potent inducer of cytokines, we determined t he 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's ho spital. Patients: Thirty children with a variety of congenital heart defects (media n 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, l ipopolysaccharide-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 s ignificantly endotoxemic prior to surgery. LBP, a plasma marker that respon ds to bacteria and endotoxin, rose significantly following cardiopulmonary bypass, as did the plasma levels of IL-6. Fifteen of 30 patients met prospe ctively defined criteria for experiencing a severe hemodynamic disturbance ill their postoperative course. These patients had significantly higher pre operative plasma LBP (p < 0.02) and plasma endotoxin levels (p < 0.05), com pared to patients with less-severely disturbed hemodynamics. Mortality was 25% in patients with preoperative endotoxemia, compared with no mortality i n patients who were not endotoxemic before surgery (p = 0.05). Conclusions: These data demonstrate that endotoxemia in children with conge nital heart disease is more common than previously suspected, and is associ ated with clinical outcomes. We conclude that clinical trials targeting end otoxin will be necessary to determine if endotoxin is a causal, etiologic a gent in the disease process.