Phosphorylcholine-coated cardiopulmonary bypass in paediatric cardiac surgery improves biocompatibility: reduced contact activation and endothelin-1 release

Introduction

Modification of cardiopulmonary bypass (CPB) circuits by using a phospholipid coating is a promising option for improving biocompatibility of CPB and thus reducing CPB-associated organ dysfunction. Endothelin-1 is a potent vasoconstrictor peptide that is synthesized and secreted by vascular endothelial cells. Its biological functions are widespread, acting as a mitogen and stimulant of collagen synthesis. It has been reported to be positively inotropic, to increase after vascular injury, and to induce pulmonary vasoconstriction, cardiac hypertrophy and heart failure. The aim of this study was to analyze the impact of a new phospholipid coating with respect to contact activation and endothelin-1 release in paediatric cardiac surgery patients.

Method

We randomly assigned 20 neonates and young children to two groups, using a completely phospholipid-coated CPB circuit in group A (n = 10) and an equivalent but uncoated set in group B (n = 10). The children were scheduled for elective congenital heart surgery. Their parents gave informed consent, and the study was approved by the local ethics committee. Arterial blood samples were drawn at times 0, 30 min and 48 h, and analyzed using enzyme-linked immunosorbent assay. The intensive care unit (ICU) course and further recovery was studied with regard to the alveolar-arterial oxygen gradient, the respiratory index, and duration of intubation and ICU stay.

Results

In group A mean age was 11.3 ± 4 days (range 6-24 days), with a mean body weight of 3.8 ± 0.2 kg (range 3.5-4.0 kg). In group B mean age was 172 ± 148 days (range 7-528 days, median 154 days), with a mean body weight of 4.8 ± 1.1 kg (range 3.0-5.9 kg). The average perfusion time in group A was 125.8 ± 25.6 min, and in group B it was 78.5 ± 33.8 min; the mean cross-clamp time in group A was 44.3 ± 17.9 min, and in group in B it was 31 ± 16.8 min. In both groups a significant loss of complement factors was observed: in group A C3c 0.45 mg/ml versus 0.71 mg/ml, C4 0.08 versus 0.14 mg/ml; and in group B C3c 0.28 mg/ml versus 0.68 mg/ml, C4 0.05 versus 0.13 mg/ml. The difference between the groups (0.45 versus 0.28, and 0.08 versus 0.05) is significant for C3, but not for C4. In both groups, complement factors normalized after 48 h. Endothelin-1 release was significantly reduced in the phospholipid group, whereas in group B elevated levels could be observed even after 48 h. The respiration parameters, such as alveolar-arterial oxygen gradient and respiratory index, revealed advantages for group A (240 ± 101 versus 375 ± 105, and 0.70 versus 1.60, respectively). Parameters such as duration of intubation and ICU stay should be considered with caution, because of the interindividual range of postoperative courses.

Conclusion

Phospholipid-coating of CPB circuit elements in paediatric cardiac surgery leads to a lower C3 consumption, which can also be observed with regard to C4. Improvement in biocompatibilty is evident by reduced endothelin-1 release, which may lead to decreased vasoconstriction and thus to a decrease in cardiac afterload in postischaemic myocardium. The reduction in oxygen consumption is likely to improve clinical outcome. Clinical parameters such as respiration and duration of ICU stay indicate beneficial effects for phospholipid-treated patients; this needs confirmation in further studies including many more patients, as have already been initiated.