Bradykinin and histamine generation with generalized enhancement of microvascular permeability in neonates, infants, and children undergoing cardiopulmonary bypass surgery.

Objective: To investigate whether generation and liberation of bradykinin and histamine contribute to generalized edema formation in pediatric cardiopulmonary bypass surgery.

Design: Prospective observational study.

Setting: Pediatric heart surgery of a university hospital.

Patients: Forty-one neonates, infants, and children undergoing cardiopulmonary bypass to correct congenital cardiac anomalies.

Interventions: Plasma concentrations of bradykinin and histamine were determined before, during, and after cardiopulmonary bypass. Fluid balance was evaluated by control of fluid intake and output.

Measurements And Main Results: The susceptibility to generalized edema formation increased significantly (r = -.457; p <.005) with decreasing age. Approximately three times higher plasma concentrations of bradykinin (p <.001) were found at the onset of anesthesia and during the total observation period in patients with a fluid retention of >6% of body weight compared with patients with a lower retention rate. Plasma bradykinin reached significantly (p <.01) higher peak concentrations of 237.9 +/- 58.6 fmol/mL during cardiopulmonary bypass and of 227.5 +/- 90.7 fmol/mL during the early postoperative period in patients with severe edema formation in contrast to only 86.6 +/- 10.9 and 65.5 +/- 26.8 fmol/mL in patients with minor fluid retention. A tendency (p =.06) to slightly increasing histamine concentrations from 2.07 +/- 0.13 nmol/L at baseline to 3.32 +/- 1.41 nmol/L during 90 mins of cardiopulmonary bypass was only observed in patients with high fluid retention.

Conclusions: Bradykinin seems to be essentially involved in the enhancement of microvascular permeability in pediatric cardiopulmonary bypass surgery, although a dominant causal role cannot be claimed by this study. Histamine, however, doesn't appear to play a major role and may only contribute as a cofactor. To what extent an increased expression of bradykinin-1 and bradykinin-2 receptors or a reduced potential of bradykinin-degrading enzymes is involved is the object of a further clinical study.