Effects of Tranexamic Acid Based on its Population Pharmacokinetics in Pediatric Patients Undergoing Distraction Osteogenesis for Craniosynostosis: Rotational Thromboelastometry (ROTEM^TM) Analysis

Abstract

Background: Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet.Methods: Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEMTM) was conducted to monitor changes in coagulation perioperatively.Results: Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group.Conclusions: TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis.

Utilization of tranexamic acid in craniosynostosis surgery

“…The institutional blood management protocol includes TXA at a loading dose of 50 mg/kg followed by a 5 mg/kg per hour infusion throughout the procedure. Intraoperative transfusion requirements depend on the transfusion guidelines (17,30,31): blood pressure drops with hematocrit (Hct) < 30%, acute bleeding resulting in a 15% estimated blood volume loss (EBVloss) during surgery, tachycardia and any clinical signs of acute anemia in the presence of Hct < 24%. However, the postoperative transfusion threshold was set to hemoglobin < 8 g/dL in the absence of hemodynamic instability.…”

Reducing blood loss in pediatric craniosynostosis surgery by use of tranexamic acid

“…Although blood loss is considered to be more difficult to evaluate, results showed similar conclusions in favour of the benefit of TXA. When considered, the mean calculated blood loss [10,14,15,18] or the estimated blood loss [19-21, 23, 24] were significantly lower in the TXA+ group, except for Dadure et al [9]. The same positive results were observed for fresh frozen plasma transfusions in the 2 recent randomized studies: significantly fewer fresh frozen plasma transfusions were required in the TXA groups [14,15].…”

“…Thirteen studies were eligible for our review. Of the 13 studies, 4 were prospective, randomized, double-blind controlled trials [9,10,14,15], 9 were retrospective studies, tailored as a "before-after" studies, comparing blood loss and transfusion without/with TXA [16][17][18][19][20][21][22][23][24]. Study characteristics are presented in Table 1 and 2.…”

“…Protocols of TXA administration varied from one study to another. A loading dose was commonly used, with doses ranging from 10 mg/kg [14,15,18,[20][21][22] to 100 mg/kg [16], usually infused over 15 minutes after induction of general anesthesia and before skin incision. A continuous infusion until skin closure was performed in all studies, with different protocols: 5 mg/kg/h [10,14,18,[20][21][22][23] or 10 mg/kg/h [9,16,17,19,24].…”

“…Various parameters were studied in these reports including age, gender, weight, primary or redo surgery, ASA status, urine output, pre-and postoperative hematocrit/hemoglobin/platelet In 10 of the 13 studies, results were obviously the same: the use of TXA significantly reduces the volume of PRBC transfusion when compared to the placebo group [9,10,14,15] or to a group without TXA [17-19, 21, 23, 24]. In 2 studies [16,20], the volume of PRBC transfused was similar between the TXA+ / TXA-groups of patients undergoing open procedures.…”