Background: The mechanism of postoperative capillary leak syndrome related to cardiopulmonary bypass (CPB) is unknown. The authors hypothesized that C4 gene polymorphism might be involved in the development of the syndrome because complement activation is associated with CPB and protamine administration, and the two isotypes of C4 (C4A and C4B) differ in their biochemical and functional properties after activation.
Methods: One hundred fifty-six pediatric patients referred for elective cardiac surgery with CPB were included in the study. C4 isotype studies were performed in plasma samples obtained before surgery, with use of agarose gel immunofixation and crossed immunoelectrophoresis. Five possible C4 phenotype groups were observed, which were abbreviated as follows: (1) AABB = no detectable null alleles, (2) A0BB = a single null allele (heterozygous) at the C4A locus, (3) 00BB = a homozygous C4A null allele, (4) AAB0 = a single null allele (heterozygous) at the C4B locus, and (5) AA00 = a homozygous C4B null allele. The patients were classified into five groups according to their C4 phenotypes. Before CPB and at 1 h after CPB, plasma protein was measured with a biuret test kit. Plasma colloid osmotic pressure was determined with a membrane osmometer. Evans blue dye was used to measure plasma volume, serum protein, intravenous protein pool, and transvascular escape rate of Evans blue dye.
Results: Of 156 pediatric patients enrolled, 80 were assigned to the AABB group, 28 were assigned to the A0BB group, 7 were assigned to the 00BB group, 31 were assigned to the AAB0 group, and 10 were assigned to the AA00 group, according to their C4 phenotypes. At 1 h after CPB, serum protein concentrations averaged 3.6 +/- 0.4 g/dl in patients with the 00BB C4 phenotype; this value was significantly lower (P < 0.01) than that in patients with other C4 phenotypes. The changes of intravenous protein pool and colloid osmotic pressure were comparable with the change in serum protein concentration. At 1 h after CPB, the transvascular escape rate of Evans blue dye averaged 11.5 +/- 1.3%/h in patients with the 00BB C4 phenotype; this value was significantly higher (P < 0.01) than that in patients with other C4 phenotypes.
Conclusions: In this study, capillary leak syndrome induced by CPB occurred only in patients with the homozygous C4A null phenotype.