We appreciate the interest of Meyer et al.  in our article and thank them for their thoughtful comments. We would like to respond to each comment individually.

We agree with Meyer and the editorial viewpoint by Holcomb that tranexamic acid (TXA) “works, but how?… and in whom?”1The goal of our study was to investigate the efficacy of TXA in craniosynostosis surgery in a defined group of children at our institution. Therefore, we determined that “it works” in our patient population of children aged 6 months to 6 yr having craniosynostosis reconstruction surgery. We agree that the exact mechanism of action is not fully understood and requires further research.

We agree with Meyer et al.  in their statement that “to be relevant, clinical studies” need to have “a valuable evaluation of perioperative blood losses” (as they point out, we used calculated blood loss instead of the estimated blood loss, which is inaccurate) and “need for strict hemodilution guidelines.” Indeed, we performed strict hemodilution in our study and administered conservative volumes of crystalloids/colloids to maintain safe and stable mean arterial blood pressure of 45 mmHg or greater without using medication for pressure support. As pointed out by Meyer et al. , there tends to be rapid and substantial blood loss during craniosynostosis surgery that can lead to persistent hypotension, permanent neurologic impairment, cardiac arrest, and death.2Our standard intraoperative approach for treating rapid blood loss is similar to that reported in the literature and by Meyer's own institution: “Isovolemic compensation of blood loss was strictly observed with fluid replacement based upon hemodynamic variables (to maintain mean arterial blood pressure in range of 45–55 mmHg) using colloid and blood transfusion.”3,4 

We disagree with Meyer et al.  for characterizing our study as including “acute normovolemic hemodilution,” which is defined as “an autologous blood collection technique involving removal of blood from a patient on the day of surgery shortly before surgical blood loss.”5Our study did not include this technique.

In our study, the hematocrit threshold for blood transfusion was not 30%, as Meyer et al.  suggest. It was 25% (hemoglobin of approximately 8g/dl), as stated on page 863 in the Materials and Methods section.6 

It is true that all our patients required transfusion intraoperatively; however, we concluded that TXA significantly reduced the volume of packed erythrocytes transfused by a mean value of 32%. In addition, TXA significantly reduced the calculated blood loss by a mean value of 38% intraoperatively and 72% during the first 24 h after surgery. Furthermore, none of the children in the TXA group required blood transfusion in the first 24 h postoperatively, whereas 50% who did not receive TXA required transfusion. TXA administration significantly diminished (by two-thirds) the exposure of patients to transfused blood compared to placebo (medians: 1 unit vs.  3 units, P < 0.001).

We do not concur with the conclusions Meyer et al.  drew by comparing two study doses of different trial designs. Our study used TXA alone, and Dadure et al.  used a combination of TXA and pretreatment with erythropoietin.7,6 

Meyer et al.  have misread our study; we did not include “faciosynostosis,” nor did our patient population require “various types of procedures.” Our patient collective had major reconstruction surgeries that involved fronto-orbital advancement and cranial vault reconstruction with an average of 70 ± 18% of the entire skull bone undergoing reconstructive surgery. The procedures were performed by the same pediatric neurosurgeon and one of two plastic surgeons.

Meyer et al. 's statement that “including, in a small sample of patients, numerous subgroups requiring various surgical managements could significantly attenuate the power of a study” is not relevant to our study. We are not sure to which “subgroups” or which “various surgical managements” they are referring. Our randomized controlled trial simply consisted of craniosynostosis patients requiring major craniofacial reconstructive surgery.

We agree with Meyer et al.  that the type of surgical procedure is an important predictor of blood loss. However, it is not the only major determinant, as it is well known that certain high-risk groups, such as those with recognized craniofacial syndromes, pansynostosis, operating time greater than 5 h, and age of 18 months or younger at the time of the procedure, have significantly greater blood loss during craniosynostosis repair.8Furthermore, our study and other studies support the fact that there is an inverse relationship between the child's age and the amount of blood loss and transfusion requirements during craniosynostosis reconstructive surgery.6,8,,10Blood loss during craniosynostosis surgery may seem to be disproportionately greater in infants (less than 10 kg) than older children because the head represents a larger percentage of total body surface area.11These high-risk groups in particular may benefit from TXA.

We agree with Meyer et al.  that a large-scale study is needed to verify the findings of studies with small sample sizes. This will require multicenter collaboration. However, we disagree that the patients who would benefit most are those with “simple suture involvement,” because all craniosynostosis patients would surely benefit from “efficient adjunctive techniques to reduce intraoperative blood loss.”

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Dahmani S, Orliaguet GA, Meyer PG, Blanot S, Renier D, Carli PA: Perioperative blood salvage during surgical correction of craniosynostosis in infants. Br J Anaesth 2000; 85:550–5
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Dadure C, Sauter M, Bringuier S, Bigorre M, Raux O, Rochette A, Canaud N, Capdevila X: Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: A randomized double-blind study. ANESTHESIOLOGY 2011; 114:856–61
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Faberowski LW, Black S, Mickle JP: Blood loss and transfusion practice in the perioperative management of craniosynostosis repair. J Neurosurg Anesthesiol 1999; 11:167–72
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