Intraoperative Tranexamic Acid Reduces Blood Transfusion in Children Undergoing Craniosynostosis Surgery A Randomized Double-blind Study

ArticleinAnesthesiology 114(4):856-61 · February 2011with135 Reads
DOI: 10.1097/ALN.0b013e318210f9e3 · Source: PubMed
Abstract
Surgical correction of craniosynostosis in children is associated with substantial intraoperative bleeding. Tranexamic acid (TXA) decreases intraoperative blood loss during cardiac or orthopedic surgery in children. We hypothesized that intraoperative TXA would reduce blood transfusion relative to placebo in patients pretreated with erythropoietin. Forty consecutive children, American Society of Anesthesiologists status 1 or 2, scheduled to undergo surgical correction of craniosynostosis were randomly assigned to receive either intravenous TXA or saline, 0.9%, intraoperatively. All children received preoperative erythropoietin (600 U/kg once a week for 3 weeks before surgery). Perioperative blood loss, number and volume of transfusions, percentage of children who underwent transfusion, and side effects were noted after surgery and at the end of the study. Surgeon satisfaction and cost of treatment were also recorded. There was no significant difference between groups in demographic or surgical data. In the TXA group, the volume of packed erythrocytes transfused was significantly reduced by 85% (from 11 to 1.6 ml/kg) intraoperatively and by 57% (from 16.6 to 7.2 ml/kg) throughout the study period (P < 0.05). Compared with the placebo group, the percentage of children requiring blood transfusion was lower in the TXA group during surgery (9 [45%] of 20 vs. 2 [11%] of 19 children; P < 0.05) and during the whole study period (14 [70%] of 20 vs. 7 [37%] of 19; P < 0.05). Preoperative and postoperative hematologic parameters were comparable in both groups. There were no adverse events. In children undergoing surgical correction of craniosynostosis and pretreated with erythropoietin, intraoperative TXA reduces the transfusion requirement.
    • "L'évaluation objective des pertes sanguines par le calcul de ces dernières selon une formule prédéfinie incluant le poids du patient, l'hématocrite pré et postopératoire et le volume de culots globulaires transfusés pourrait permettre, outre son intérêt dans l'optimisation de la stratégie transfusionnelle, de comparer les pertes sanguines entre différentes techniques chirurgicales, entre chirurgiens et même entre institutions et ainsi de fournir un outil intéressant en termes d'évaluation des pratiques et notamment des stratégies d'épargne transfusionnelle. Lors de chirurgies céphaliques ou extracéphaliques, d'autres auteurs se basent davantage sur les pertes sanguines mesurées (PSM) dans l'aspiration chirurgicale, éventuellement associées à la pesée des champs et des compresses chirurgicales, pour évaluer le saignement peropératoire [1,111213141516. L'évaluation des PSM est souvent biaisée et peu corrélée aux valeurs de l'hémoglobine et de l'hématocrite [2]. "
    [Show abstract] [Hide abstract] ABSTRACT: L’objectif de cette étude était de comparer les PSC (pertes sanguines calculées) et les PSM (pertes sanguines mesurées) pour l’appréciation du saignement peropératoire lors de l’exérèse de tumeurs intracrâniennes par craniotomie chez l’enfant. Étude rétrospective monocentrique sur une période de 2 ans incluant les exérèses de tumeurs cérébrales par craniotomie chez l’enfant. Les pertes sanguines peropératoires étaient mesurées, et calculées selon une formule précédemment décrite. Une étude de corrélation de Spearman entre PSC et PSM était effectuée, ainsi qu’une analyse de concordance selon la méthode de Bland et Altman. Quatre-vingt patients âgés de 8 ± 5 ans ont été inclus. Les PSM étaient significativement plus faibles que les PSC (4,04 [1,96–7,23] vs 11,34 [7,21–17,45] mL/kg, p < 0,0001). Il existait une corrélation modérée entre les PSM et les PSC (rho = 0,52 [intervalle de confiance à 95 % 0,34–0,66], p < 0,0001). Les PSM sous-estimaient les pertes sanguines peropératoires (biais moyen de −8,0 mL/kg) et leur précision était mauvaise (limites d’agrément de −24,2 mL/kg et 8,3 mL/kg). Nos résultats suggèrent que les PSM ne doivent pas être utilisées en pratique pour évaluer les pertes sanguines peropératoires lors de l’exérèse de tumeurs intracrâniennes pédiatriques par craniotomie, exposant aux risques de sous-estimation du saignement peropératoire et de retard transfusionnel.
    Full-text · Article · Sep 2015 · Clinical Pharmacokinetics
    • "There is a lack of dose-response in published data in the literature, where described initial bolus dosage range from 10 mg/kg to 100 mg/kg TA. In ours, continuous infusion of TA was not used after bolus dose; however, others had used continuous infusion.[2124] "
    [Show abstract] [Hide abstract] ABSTRACT: This study was conducted to evaluate the effect of tranexamic acid (TA) on the intra-operative bleeding during the functional endoscopic sinus surgery (FESS) in children. A total of 100 children recruited to undergo FESS were randomized into two groups. Group I: Was given just after induction, intra-venous 25 mg/kg TA diluted in 10 ml of normal saline. Group II: Was given 10 ml of normal saline. Non-invasive blood pressure, heart rate, and quality of the surgical field were estimated every 15 min. Volume of bleeding and duration of the surgical procedure were recorded. Surgical field quality after 15 min revealed that seven patients in group I had minimal bleeding versus no one in group II, P=0.006. Meanwhile, 35 patients in group I had mild bleeding versus 26 patients in group II, P=0.064. Higher number of patients in group II than in group I had moderate bleeding, P=0006. Also, at 30 min, revealed that 10 patients in group I had minimal bleeding versus one patient in group II, P=0.004. Meanwhile, 37 patients in group I had mild bleeding versus 28 patients in group II, P=0.059. Higher number of patients in group II than in group I had moderate bleeding, P<0001. Duration of the surgeries and volume of bleeding were significantly less in tranexamic group than the placebo group, P<0.0001. Single intra-venous bolus dose of tranexamic in children during the FESS improves quality of surgical field, reduces intra-operative bleeding, and duration of surgery.
    Article · Jul 2013
    • "Observed TXA concentrations (μg/mL) Individually post hoc-predicted TXA concentrations (μg/mL) Our simulations predicted that an optimal loading dose of 10 mg/kg over 15 min followed by a 5 mg/kg/h maintenance infusion produces steady-state TXA plasma concentrations above the presumed considered therapeutic threshold of 16 lg/mL, while reducing the initial high peaks observed with the larger dose of 50 mg/kg in our previous study [12]. Recently, similar low dosing regimens have been used in clinical studies and have shown good clinical effect [13]. However, clinical trials both in children and adults have revealed a wide variability in terms of bleeding and transfusion requirements following TXA administra- tion [12,16171819. "
    [Show abstract] [Hide abstract] ABSTRACT: BACKGROUND: Tranexamic acid (TXA) effectively reduces blood loss and transfusion requirements during craniofacial surgery. The pharmacokinetics of TXA have not been fully characterized in paediatric patients and dosing regimens remain diverse in practice. A mixed-effects population analysis would characterize patient variability and guide dosing practices. OBJECTIVE: The objective of this study was to conduct a population pharmacokinetic analysis and develop a model to predict an effective TXA dosing regimen for children with craniosynostosis undergoing cranial remodelling procedures. METHODS: The treatment arm of a previously reported placebo-controlled efficacy trial was analysed. Twenty-three patients with a mean age 23 ± 19 months received a TXA loading dose of 50 mg/kg over 15 min at a constant rate, followed by a 5 mg/kg/h maintenance infusion during surgery. TXA plasma concentrations were measured and modelled with a non-linear mixed-effects strategy using Monolix 4.1 and NONMEM(®) 7.2. RESULTS: TXA pharmacokinetics were adequately described by a two-compartment open model with systemic clearance (CL) depending on bodyweight (WT) and age. The apparent volume of distribution of the central compartment (V(1)) was also dependent on bodyweight. Both the inter-compartmental clearance (Q) and the apparent volume of distribution of the peripheral compartment (V(2)) were independent of any covariate. The final model may be summarized as: CL (L/h) = [2.3 × (WT/12)(1.59) × AGE(-0.0934)] × e(η1), V(1) (L) = [2.34 × (WT/12)(1.4)] × e(η2), Q (L/h) = 2.77 × e(η3) and V(2) (L) = 1.53 × e(η4), where each η corresponds to the inter-patient variability for each parameter. No significant correlation was found between blood volume loss and steady-state TXA concentrations. Based on this model and simulations, lower loading doses than used in the clinical study should produce significantly lower peak concentrations while maintaining similar steady-state concentrations. CONCLUSIONS: A two-compartment model with covariates bodyweight and age adequately characterized the disposition of TXA. A loading dose of 10 mg/kg over 15 min followed by a 5 mg/kg/h maintenance infusion was simulated to produce steady-state TXA plasma concentrations above the 16 μg/mL threshold. This dosing scheme reduces the initial high peaks observed with the larger dose of 50 mg/kg over 15 min used in our previous clinical study.
    Full-text · Article · Feb 2013
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