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Correspondence  |   March 2012
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Author Affiliations & Notes
  • Susan M. Goobie, M.D., F.R.C.P.C.
    *
  • *Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts.
Article Information
Correspondence
Correspondence   |   March 2012
In Reply
Anesthesiology 3 2012, Vol.116, 734-735. doi:10.1097/ALN.0b013e318244b4e0
Anesthesiology 3 2012, Vol.116, 734-735. doi:10.1097/ALN.0b013e318244b4e0
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?”1 The 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.2 Our 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.”5 Our 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.8 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.6,8  10 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.11 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.”
References
Holcomb JB: Tranexamic acid in elective craniosynostosis surgery: It works, but how? ANESTHESIOLOGY 2011; 114:737–8
Czerwinski M, Hopper RA, Gruss J, Fearon JA: Major morbidity and mortality rates in craniofacial surgery: An analysis of 8101 major procedures. Plast Reconstr Surg 2010; 126:181–6
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
Meyer P, Renier D, Arnaud E, Jarreau MM, Charron B, Buy E, Buisson C, Barrier G: Blood loss during repair of craniosynostosis. Br J Anaesth 1993; 71:854–7
Monk TG, Goodnough LT, Brecher ME, Colberg JW, Andriole GL, Catalona WJ: A prospective randomized comparison of three blood conservation strategies for radical prostatectomy. ANESTHESIOLOGY 1999; 91:24–33
Goobie SM, Meier PM, Pereira LM, McGowan FX, Prescilla RP, Scharp LA, Rogers GF, Proctor MR, Meara JG, Soriano SG, Zurakowski D, Sethna NF: Efficacy of tranexamic acid in pediatric craniosynostosis surgery: A double-blind, placebo-controlled trial. ANESTHESIOLOGY 2011; 114:862–71
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
White N, Marcus R, Dover S, Solanki G, Nishikawa H, Millar C, Carver ED: Predictors of blood loss in fronto-orbital advancement and remodeling. J Craniofac Surg 2009; 20:378–81
Stricker PA, Shaw TL, Desouza DG, Hernandez SV, Bartlett SP, Friedman DF, Sesok-Pizzini DA, Jobes DR: Blood loss, replacement, and associated morbidity in infants and children undergoing craniofacial surgery. Paediatr Anaesth 2010; 20:150–9
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
Livingston EH, Lee S: Percentage of burned body surface area determination in obese and nonobese patients. J Surg Res 2000; 91:106–10