Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination?

BACKGROUND: Children with cyanotic heart disease undergoing cardiac surgery in which cardiopulmonary bypass is used are at increased risk of postoperative bleeding. In this study, the authors investigated the possibility of reducing postoperative blood loss by using aprotinin and tranexamic acid alone or a combination of these two agents. METHODS: In a prospective, randomized, blind study, 100 children undergoing cardiac surgery were investigated. In group 1 (n = 25) patients acted as the control and did not receive either study drugs. In group 2 (n = 25) patients received aprotinin (30.000 KIU.kg(-1) after induction of anesthesia, 30.000 KIU.kg(-1) in the pump prime and 30.000 KIU.kg(-1) after weaning from bypass). In group 3 (n = 25) patients received tranexamic acid (100 mg.kg(-1) after induction of anesthesia, 100 mg.kg(-1) in the pump prime and 100 mg.kg(-1) after weaning from bypass). In group 4 (n = 25) patients received a combination of the two agents in the same manner. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. In addition, hemoglobin, platelet counts and coagulation studies were recorded. RESULTS: Postoperative blood loss was significantly higher in the control group (group 1) compared with children in other groups who were treated with aprotinin, tranexamic acid or a combination of the two agents (groups 2, 3 and 4) during the first 24 h after admission to cardiac intensive care unit (40 +/- 18 ml.kg(-1).24 h(-1), aprotinin; 35 +/- 16 ml.kg(-1).24 h(-1), tranexamic acid; 34 +/- 19 ml.kg(-1).24 h(-1), combination; 35 +/- 15 ml.kg(-1).24 h(-1)). The total transfusion requirements were also significantly less in the all treatment groups. Time taken for sternal closure was longer in the control group (68 +/- 11 min) compared with treatment groups 2, 3 and 4, respectively (40 +/- 18, 42 +/- 11, 42 +/- 13 min, P < 0.05). The coagulation parameters were not found to be significantly different between the three groups. CONCLUSIONS: Our results suggested that both agents were effective to reduce postoperative blood loss and transfusion requirements in patients with cyanotic congenital heart disease. However, the combination of aprotinin and tranexamic acid did not seem more effective than either of the two drugs alone.

Does normoxemic cardiopulmonary bypass prevent myocardial reoxygenation injury in cyanotic children?

OBJECTIVE: To evaluate whether the deleterious effect of cardiopulmonary bypass (CPB) can be prevented by controlling PaO(2) in cyanotic children. DESIGN: Prospective, randomized, clinical study. SETTING: Single university hospital. PARTICIPANTS: Pediatric patients undergoing cardiac surgery for repair of congenital heart disease (n = 24). INTERVENTIONS: Patients were randomly allocated into 3 groups. Patients in the acyanotic group (group I, n = 10) had CPB initiated at a fraction of inspired oxygen (F(I)O(2)) of 1.0 (PO(2), 300 to 350 mmHg). Cyanotic patients were subdivided as follows: Group II (n = 7) had CPB initiated at an F(I)O(2) of 1.0, and group III (n = 7) had CPB initiated at an F(I)O(2) of 0.21 (PO(2), 90 to 110 mmHg). A biopsy specimen of right atrial tissue was removed during venous cannulation, and another sample was removed after CPB before aortic cross-clamping. The tissue was incubated in 4 mmol/L of t-butylhydroperoxide, and the malondialdehyde (MDA) level was measured to determine the antioxidant reserve capacity. Blood samples for cytokine levels, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 response to CPB were collected after induction of anesthesia and at the end of CPB before protamine administration. MEASUREMENTS AND MAIN RESULTS: After initiation of CPB, MDA level rose markedly in the cyanotic groups compared with the acyanotic group (210 +/- 118% v 52 +/- 34%, p < 0.05), which indicated the depletion of antioxidants. After initiation of CPB, TNF-alpha and IL-6 levels of the cyanotic groups were higher than for the acyanotic group (168 +/- 77 v 85 +/- 57, p < 0.001; 249 +/- 131 v 52 +/- 40; p < 0.001). When a comparison between the cyanotic groups was performed, group II (initiating CPB at an F(I)O(2) of 1.0) had significantly increased MDA production compared with group III (initiating CPB at an F(I)O(2) of 0.21) (302 +/- 134% v 133 +/- 74%, p < 0.05). Group II had higher TNF-alpha and IL-6 levels than group III (204 +/- 81 v 131 +/- 52, p < 0.001; 308 +/- 147 v 191 +/- 81, p < 0.01). CONCLUSION: Conventional clinical methods of initiating CPB at a hyperoxemic PO(2) may increase the possibility of myocardial reoxygenation injury in cyanotic children. This deleterious effect of reoxygenation can be modified by initiating CPB at a lower level of oxygen concentration. Subsequent long-term studies are needed to determine the best method of decreasing the oxygen concentration of the CPB circuit.