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.
prospective, observational study.
Setting: A large,
urban, university-affiliated, tertiary-care children’s hospital.
Patients: Thirty children with a variety of congenital
heart defects (median age, 59 days; median weight, 4.0 kg) were
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
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 < 0.02) and plasma endotoxin levels
(p < 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).
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.