Puzzling ENIGMA: cost-benefit analysis of nitrous oxide.

more, 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. 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 highrisk 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. Furthermore, 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. Blood 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. These 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.”