Is the precise control of circulating heparin levels during cardiopulmonary bypass beneficial in paediatric open-heart surgery?

Objectives

Despite careful monitoring of anticoagulation during cardiopulmonary bypass (CPB) by means of activated coagulation time (ACT), thrombin generation does occur at variable rates, initiating several pro-inflammatory reactions. The mechanisms responsible for this activation of the coagulation cascade include inadequate heparinisation, often masked by hypothermia and haemodilution. The objective of this study was to compare the effects of two methods of managing anticoagulation during CPB in infants and children.

Methods

Twenty patients, aged 4 months to 17 years, undergoing elective cardiac surgery were prospectively randomized to receive either a standard dose of heparin (300 IU/kg) (Group A, n = 10) or a dose sufficient to achieve a whole blood heparin concentration [Hep]=4.8 IU/ml (Group B, n = 10). ACT was maintained > 480 s in both groups. [Hep] was measured by on-site testing with a heparin-protamine titration method (HMS, Medtronic, Inc.). The following variables were studied: prothrombin fragments (PF1+2), D-dimers (D-d), β-thromboglobulin (β-TG), platelet count, postoperative blood losses, standardized blood and blood products administration, intensive care and hospital stay.

Results

The groups were comparable with regards to age, weight, disease complexity, duration of CPB and a number of other variables. The results are summarized in the Table.

Blood losses during the first 24 h (26.4 ± 4.7 vs 15.2 ± 3.7 ml/kg/24 h, P = 0.05) and requirement for transfusion of blood (11.4 ± 3.6 vs 3.1 ± 1.3 ml/kg, P = 0.05) and fresh frozen plasma (6.1 ± 2.2 vs 0.9 ± 0.3 ml/kg, P = 0.09) were lower in Group B, when compared to Group A.

Table 1

Conclusions

Management of anticoagulation during CPB aiming to achieve and maintain an [Hep] significantly higher than 'normal' results in less activation of the coagulation cascade, lower fibrinolysis, and lower blood losses and need for tranfusions. Further studies, on a larger number of children, are warranted to better define the clinical impact of these findings.