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Effect of heparin loading during congenital heart operation on thrombin generation and blood loss
S O Turner-Gomes1, E P Nitschmann, G R Norman
1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Insights
Higher heparin doses during pediatric cardiopulmonary bypass (CPB) increased plasma heparin levels but did not significantly alter thrombin generation or postoperative blood loss. Further research is needed to optimize heparin dosing for children with congenital heart disease undergoing CPB.
Area of Science:
- Cardiovascular Surgery
- Pediatric Cardiology
- Pharmacology
Background:
- Current heparin protocols for pediatric cardiopulmonary bypass (CPB) are based on adult data.
- Children exhibit increased heparin clearance compared to adults, necessitating specific dosing studies.
- Optimal heparin dosing is crucial for children undergoing surgical repair for congenital heart disease.
Purpose of the Study:
- To assess the impact of two different heparin doses in the CPB prime solution on heparin levels, thrombin generation, and hemorrhage risk.
- To evaluate the efficacy of higher heparin concentrations in pediatric CPB.
Main Methods:
- A prospective study involving 48 children with congenital heart disease undergoing CPB.
- Patients received a loading dose of heparin followed by either 1 U/mL (low-dose) or 3 U/mL (high-dose) in the prime solution.
- Measurements included plasma heparin levels, thrombin-antithrombin III complexes, prothrombin fragment 1 + 2, D-dimer, antithrombin III, and postoperative blood loss.
Main Results:
- CPB consistently led to thrombin generation in all patients.
- Higher heparin doses (3 U/mL) resulted in elevated plasma heparin levels and a trend toward lower D-dimer levels.
- Increased heparin dose did not significantly affect postoperative blood loss, though cyanotic patients experienced higher blood loss.
Conclusions:
- Increasing heparin prime concentration from 1 to 3 U/mL elevates plasma heparin levels and may reduce markers of fibrinolysis.
- Thrombin generation and postoperative hemorrhage were not significantly impacted by the increased heparin dose.
- Further randomized trials are required to establish optimal heparin dosing regimens for pediatric congenital heart disease patients undergoing CPB.
Background:
The heparin protocols used during cardiopulmonary bypass (CPB) in children undergoing surgical repair for congenital heart disease are extrapolated from adult data. Studies are needed that assess the optimal heparin dosing in these children, whose heparin clearance is increased compared with that in adults.
Methods:
We assessed the effects of two commonly used doses of heparin in the prime solution at the start of CPB operation on plasma heparin levels, on thrombin production (thrombin-antithrombin III complexes, prothrombin fragment 1 + 2, D-dimer, and antithrombin III), and on the risk of hemorrhage. Before CPB, 48 children with congenital heart disease received heparin intravenously in a loading dose of 300 U/kg, followed by either 1 U/mL of heparin in the prime (low-dose group: 22 patients-acyanotic, 9; cyanotic, 13) or 3 U/mL of heparin in the prime (group: high-dose, 26 patients-acyanotic, 15; cyanotic, 11).
Results:
In all patients, CPB resulted in the generation of thrombin. The duration of CPB was a significant covariate factor for heparin levels (p = 0.002), thrombin production (p < 0.001), and postoperative blood loss (p < 0.001). In the patients in the high-dose group, the total heparin dose and the plasma heparin levels were higher (p = 0.0005 and 0.005, respectively) and the D-dimer levels tended to be lower (p = 0.06). The postoperative blood loss was higher in the cyanotic patients (p = 0.02; both high-dose and low-dose groups), with 2 cyanotic patients (1 in low-dose group, 1 in high-dose group) requiring reoperation, one of whom subsequently died. The increased heparin dose had no significant effect on the rate or volume of postoperative blood loss.
Conclusions:
Increasing the heparin dose in the prime solution from 1 to 3 U/mL increased the plasma heparin levels and showed a trend toward reducing the postoperative laboratory values indicative of fibrinolysis. Thrombin generation during CPB and the incidence of postoperative hemorrhage were not significantly altered. Larger randomized trials are needed to determine the optimal heparin-dosing regimen in patients with congenital heart disease.