Tranexamic Acid In Children Research Articles

Does tranexamic acid reduce blood loss for children undergoing reconstruction for neuromuscular hip dysplasia? A matched comparative study.

Treatment for neuromuscular hip dysplasia (NMHD) typically involves osteotomies of the proximal femur and/or pelvis, and the potential for significant volume blood loss is high. Tranexamic acid (TXA) functions as an antifibinolytic and has been shown to reduce bleeding in many operative settings. Retrospective evidence for the use of TXA in children undergoing NMHD reconstruction is inconclusive, and to our knowledge, prospective evaluation has never been performed. The purpose of this study was to examine the effectiveness of TXA use on intra- and postoperative outcomes during bony reconstruction for NMHD. In this matched comparative study, a prospective cohort of patients undergoing bony reconstruction for NMHD who were given TXA was enrolled and then matched to a retrospective cohort who previously underwent the same surgery without administration of TXA. The primary outcome variable was a change in perioperative hemoglobin values from preoperative to 1 day postoperatively. Secondary objectives were percent loss of estimated blood volume, postoperative transfusion requirements, and length of hospital stay. Forty-eight patients, 24 in each cohort, were included in the analyses. Mean age at surgery was 7.09 years (±2.5). Fifty percent of each cohort underwent bilateral varus derotational osteotomy with pelvic acetabuloplasty. No statistical differences were found in postoperative hemoglobin differences (P = 0.18), length of hospital stay (P = 0.45), or blood transfusion requirements (P = 0.56) between cohorts. Intraoperative administration of TXA to patients undergoing bony reconstruction for NMHD was not found to reduce postoperative blood loss or requirement for blood transfusion. Future studies should employ a larger, prospective randomized controlled trial to verify these findings.

Potential Benefit of Combined Topical and Intravenous Administration of Tranexamic Acid in Congenital Heart Surgery

Abstract Objective Pediatric patients who undergo repair of congenital heart diseases on cardiopulmonary bypass are at great risk of postoperative bleeding. The major causes of bleeding are thrombocytopenia, platelets dysfunction, hemodilution and increased fibrinolysis during cardiopulmonary bypass (CPB). Non-surgical postoperative bleeding occurs due to micro-vascular bleeding from pericardial and mediastinal tissues when blood comes in contact with non-endothelial surfaces of the Cardio-Pulmonary Bypass (CPB) machine, compounded by liberal use of heparin and a complex interaction of humoral and cellular pathways. Aim of the Work The aim of the study is to asses if there is potential benefit of intrapericardial topical application of tranexamic acid when it is combined with the intravenous administration in reduction of postoperative bleeding after pediatric cardiac surgery on cardiopulmonary bypass (CPB). Patients and Methods Type of the study: Interventional, randomized and double blinded clinical trial. Study Setting: The operating theaters of Ain Shams University Hospitals. Study period: Over one year (from March 2020 to March 2021). Standard management: Intravenous Tranexamic acid (TxA) injection. Results The estimated blood loss postoperatively in first 24 hrs. Were less in the combined group than the IV group. Requirements of blood transfusion also were statically significant in combined group than IV group from aspects of volume of PRBCs transfusion, Total number of patients exposed to transfusion and transfusion rate. There is no difference regarding ICU stay and need of surgical re exploration. Conclusion The combined use of low dose IV and topical intrapericardial tranexamic acid in children with congenital heart disease undergoing on pump cardiac surgery reduced the risk of post-operative bleeding and need for blood products transfusion when compared to the administration of IV tranexamic acid only suggesting a potential benefit of topical tranexamic acid in hemostasis.

Major Trauma and the use of Tranexamic Acid in Children

Objective was to determine reduction in blood loss in children with major trauma with or without using Tranexamic acid Methods: A study included 260 patients admitted to pediatric surgery departments at Mayo Hospital, Children's Hospital, and Jinnah Hospital in Lahore, from September, 2018 to April, 2019. Patients were divided into Tranexamic acid and control groups. Both groups received standard treatment and blood transfusion requirements. Patients were followed for length of stay and final outcomes. Results: Mean injury severity score in case and control groups was 26.61±11.17 and 29.00±11.64 respectively. Mean hospital stay was significantly shorter (p = 0.002], massive blood transfusions were significantly low [3.8% vs. 38.46%, p-value<0.001] and need of surgery [24.6% vs. 46.15%, p <0.001]. Mortality rate 1.54% vs. 7.69%, p =0.018 and discharge rate 98.64% vs. 92.31%,p = 0.018). Blood transfusion requirement and need of surgery were significant predictors for mortality in this study. Conclusion: Results of this study demonstrate that Tranexamic Acid can be effectively used to minimize blood transfusion requirement in children with major trauma. It effectively reduces the need of massive blood transfusion, minimizing mortality and shortens the hospital stay for pediatric patients. Keywords: Tranexamic acid, Effectiveness, Blood loss, Children, Trauma

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): A pilot randomized trial.

The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We assessed the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries. Severely injured children (0 up to 18th birthday) were randomized into a double-blind randomized trial of (1) TXA 15mg/kg bolus dose, followed by 2mg/kg/h infusion over 8h, (2) TXA 30mg/kg bolus dose, followed by 4mg/kg/h infusion over 8h, or (3) normal saline placebo bolus and infusion. The trial was conducted at four pediatric Level I trauma centers in the United States between June 2018 and March 2020. We enrolled patients under federal exception from informed consent (EFIC) procedures when parents were unable to provide informed consent. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The target enrollment rate was at least 1.25 patients per site per month. A total of 31 patients were randomized with a mean age of 10.7years (standard deviation [SD] 5.0years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4h (SD 0.6h). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (nine patients TXA 15mg/kg bolus dose, 10 patients TXA 30mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified. Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large-scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.

Effectiveness and safety of tranexamic acid in pediatric trauma: A systematic review and meta-analysis

ObjectiveTrauma is the leading cause of childhood death in the United States. Our goal was to determine the effectiveness of tranexamic acid (TXA) in improving survival in pediatric trauma. MethodsMEDLINE (OVID), Embase (OVID), Cochrane Central Register databases, CINAHL (EBSCO), Web of Science (Clarivate Analytics), and grey literature sources were searched for publications reporting survival and safety outcomes in children receiving TXA in acute trauma, with no language restrictions, published until February 11, 2021. Two independent researchers assessed studies for eligibility, bias, and quality. Data on the study setting, injury type, participants, design, interventions, TXA dosing and outcomes were extracted. The primary outcome was survival in children who received TXA following trauma. Forest plots of effect estimates were constructed for each study. Heterogeneity was assessed and data were pooled by meta-analysis using a random-effects model. ResultsFourteen articles met inclusion criteria - six single-institution and eight multicentre retrospective cohort studies. Overall, TXA use was not associated with increased survival in pediatric trauma (adjusted odds ratio [aOR]: 0.61, 95% CI: 0.30–1.22) after adjustment for patient-level variables, such as injury severity. Increased survival was documented in the subset of children experiencing trauma in combat settings (aOR for mortality: 0.31, 95% CI: 0.14–0.68). There were no differences in the odds of thromboembolic events (OR 1.15, 95% CI: 0.46–2.87) in children who received TXA versus not. ConclusionsThe utility of TXA in children with trauma is unclear. Guidelines supporting TXA use in pediatric trauma may not be based on the available evidence of its use in this context. Rigorous trials measuring survival and other meaningful outcomes and exploring optimal TXA dosing are urgently needed.Study Registration (PROSPERO): CRD42020157683.

The design of a Bayesian adaptive clinical trial of tranexamic acid in severely injured children

BackgroundTrauma is the leading cause of death and disability in children in the USA. Tranexamic acid (TXA) reduces the blood transfusion requirements in adults and children during surgery. Several studies have evaluated TXA in adults with hemorrhagic trauma, but no randomized controlled trials have occurred in children with trauma. We propose a Bayesian adaptive clinical trial to investigate TXA in children with brain and/or torso hemorrhagic trauma.Methods/designWe designed a double-blind, Bayesian adaptive clinical trial that will enroll up to 2000 patients. We extend the traditional Emax dose-response model to incorporate a hierarchical structure so multiple doses of TXA can be evaluated in different injury populations (isolated head injury, isolated torso injury, or both head and torso injury). Up to 3 doses of TXA (15 mg/kg, 30 mg/kg, and 45 mg/kg bolus doses) will be compared to placebo. Equal allocation between placebo, 15 mg/kg, and 30 mg/kg will be used for an initial period within each injury group. Depending on the dose-response curve, the 45 mg/kg arm may open in an injury group if there is a trend towards increasing efficacy based on the observed relationship using the data from the lower doses. Response-adaptive randomization allows each injury group to differ in allocation proportions of TXA so an optimal dose can be identified for each injury group. Frequent interim stopping periods are included to evaluate efficacy and futility. The statistical design is evaluated through extensive simulations to determine the operating characteristics in several plausible scenarios. This trial achieves adequate power in each injury group.DiscussionThis trial design evaluating TXA in pediatric hemorrhagic trauma allows for three separate injury populations to be analyzed and compared within a single study framework. Individual conclusions regarding optimal dosing of TXA can be made within each injury group. Identifying the optimal dose of TXA, if any, for various injury types in childhood may reduce death and disability.

Enrollment with and without exception from informed consent in a pilot trial of tranexamic acid in children with hemorrhagic injuries.

Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries. We conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC. We enrolled one of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, seven (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12months. In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.

ε-Aminocaproic acid versus tranexamic acid in children undergoing complex cranial vault reconstruction for repair of craniosynostosis.

Complex cranial vault reconstruction (CCVR) for pediatric craniosynostosis is a high blood loss surgery, for which antifibrinolytic agents have been shown to reduce bleeding and transfusion requirements. The relative efficacy of ε-aminocaproic acid (EACA) versus tranexamic acid (TXA) has not yet been evaluated in this population. The aim of this retrospective study was to compare perioperative blood loss and transfusion in CCVR patients receiving EACA versus TXA. In a CCVR cohort of 95 children, 47 received EACA and 48 received TXA. We found no differences in demographics, adverse outcomes, calculated blood loss (CBL), or transfusion requirements between the two antifibrinolytic groups.

A Pilot Study to Evaluate the Feasibility of Anti-Fibrinolytic Agents in Reducing Hemorrhagic Complications in Pediatric Patients with Thrombocytopenia

Background: The risk of bleeding remains high in thrombocytopenic pediatric hematology-oncology patients despite the use of prophylactic platelet transfusions. In one study, WHO grade 2 or higher bleeding occurred in >80% of pediatric subjects receiving hematopoietic stem cell transplantation or chemotherapy despite a platelet transfusion threshold of 10,000/µl. The risk of bleeding is not decreased with higher transfusion thresholds or increased platelet doses. Bleeding episodes are associated with increased mortality rates, greater utilization of resources and increased transfusion requirements. We examined the use of anti-fibrinolytic agents in decreasing bleeding events and platelet transfusions. Methods: We conducted a randomized double-blinded Phase 2 trial of tranexamic acid versus placebo in inpatient pediatric patients undergoing chemotherapy or HSCT expected to have prolonged thrombocytopenia. All patients admitted to the Oncology or HSCT services were screened for eligibility. Patients consenting for enrollment received either tranexamic acid 10m/kg/dose or normal saline every 8 hours while the platelet count as <30,000/ul until discharge or spontaneous platelet recovery (maximum 30 days). We conducted daily hemostatic assessments using the WHO bleeding scale and monitored adverse events and platelet transfusion requirements. Follow-up assessments took place at 7 and 30 days following completion of study medication. Primary aims were to assess safety and feasibility of tranexamic acid in children with hypoproliferative thrombocytopenia. Results: We screened 697 admissions over 11 months, 31 patients were eligible for enrollment. Enrollment was suspended in March 2020 for COVID reasons though screening continued through July 2020. An additional 10 eligible patients were identified in this period. The most common reasons for ineligibility included recent asparaginase administration, predicted inpatient stay <5 days and age ≤ 2 or ≥ 18 years. Eleven patients enrolled and completed all study procedures. There were no missed doses of medication, 88.4% of doses were administered within one hour of prescribed time. Patients remained on study for a mean of 11.1 days. Five patients each met criteria for spontaneous platelet count recovery or discharge, 1 patient received the study medication for 30 days. Bleeding (all grades) occurred on 29.5% of days. Grade 2 or higher bleeding occurred on 4.9% of days and was experienced by 27.3% of patients. The most common sites of bleeding were oral/nasal and cutaneous. Subjects received a median of 2 platelet transfusions per patient. There were no thromboembolic events or serious adverse events. Conclusion: Tranexamic acid is well tolerated can be safely administered to pediatric oncology patients as an adjunct to therapy. We are planning a multi-center randomized controlled trial to assess the efficacy of tranexamic acid in reducing bleeding complications in this population. Disclosures Triulzi: Fresenius Kabi: Consultancy; Cerus Corp: Research Funding. OffLabel Disclosure: Tranexamic Acid - This medication is being studied as an adjuvant to therapy to prevent bleeding complications and reduce platelet transfusions in pediatric patients with hypoproliferative thrombocytopenia.

Outcome of Early Hemostatic Intervention in Children With Sepsis and Nonovert Disseminated Intravascular Coagulation Admitted to PICU: A Randomized Controlled Trial.

Evaluation of the outcome of early hemostatic management of disseminated intravascular coagulopathy in patients with severe sepsis/septic shock admitted to PICU, before the development of clinically overt disseminated intravascular coagulopathy. Prospective interventional, open label randomized controlled clinical trial. PICU at Alexandria University Children's Hospital. The study included 80 patients with proven severe sepsis/septic shock in nonovert disseminated intravascular coagulopathy stage. They were randomly assigned into two groups (group 1 and group 2). Specific intervention was applied for group 1 (plasma transfusion, low-dose unfractionated heparin, and tranexamic acid). All patients had assessment of Pediatric Index of Mortality 2 score, Pediatric Logistic Organ Dysfunction score, inotropic score, routine laboratory, and hemostatic tests including fibrin degradation products and d-dimers. Disseminated intravascular coagulopathy risk assessment scores were calculated on daily basis. Mortality rate was significantly higher in group 2. Progression to overt disseminated intravascular coagulopathy was significantly more common among group 2 patients than group 1 (45% and 10%, respectively) (p < 0.0001). Disseminated intravascular coagulopathyRisk Assessment Scores were significantly higher on the second and fifth days among group 2 patients. The initial specific hemostatic intervention was the only significant predictor of survival and prevention of progression to overt disseminated intravascular coagulopathy. Our results suggest that early use of a combination of fresh frozen plasma transfusion, low-dose heparin, and tranexamic acid in children with severe sepsis/septic shock in the "window of opportunity" before the development of overt disseminated intravascular coagulopathy stage was associated with better outcome for survival and prevention of progression to overt disseminated intravascular coagulopathy, with no increase in bleeding risk. Larger multicenter studies are needed to further prove this practice.

Safety and efficacy of tranexamic acid in children with cerebral palsy undergoing femoral varus derotational osteotomy: a double cohort study.

The safety and efficacy of tranexamic acid (TXA) in reducing blood loss after total joint arthroplasty and spinal fusion surgery has been well documented. However, little data exist regarding the effectiveness of intraoperative TXA in children with cerebral palsy (CP). The aim of this double cohort study is to investigate the safety and efficacy of intraoperative TXA in reducing blood loss and transfusion requirements for children with CP undergoing a proximal unilateral or bilateral femoral varus derotational osteotomy (VDRO). A retrospective review was performed of all paediatric theatre lists between May 2012 and January 2019 for all paediatric (< 16years old) CP patients who underwent unilateral or bilateral VDRO combined with soft tissue release at our institution. Fifty-one patients were included in our study further subdivided into two individual groups, unilateral and bilateral VDRO. No statistically significant differences were found in demographics such as age, weight, ASA, GMFCS and antiepileptic medication between the groups. However, there were significant statistically differences in TBL and transfusion rates between the groups that received TXA and those that did not, both in unilateral [241ml (TXA) vs. 369ml (non-TXA)] and bilateral [287ml (TXA) vs. 467ml (non-TXA)] operations. TXA successfully reduced TBL (in both TXA subgroups) and the transfusion rates without associated complications. TXA's safety and efficacy should be explored further in adequately powered randomized controlled trials.

Consensus Panel Algorithm for Blood Transfusions in Pediatric Trauma

In the course of designing a trial to test tranexamic acid in children with severe trauma, the Pediatric Emergency Care Applied Research Network

Development of transfusion guidelines for injured children using a Modified Delphi Consensus Process.

There is wide variability of transfusion practices for children with hemorrhagic injuries across trauma centers. We are planning a multicenter, randomized clinical trial evaluating tranexamic acid in children with hemorrhage. Standardization of transfusion practices across sites is important to minimize confounding. Therefore, we sought to generate consensus-based transfusion guidelines for the trial. We used a modified Delphi process utilizing a multi-site, multi-disciplinary panel of experts to develop our transfusion guidelines. A survey of 23 clinical categories on various aspects of transfusion practices was developed and distributed via SurveyMonkey®. Statements were graded on a 5-point Likert scale ("Strongly agree" to "This intervention may be harmful"). Statements were accepted if ≥ 80% of the panelists rated the statement as "Strongly agree" or "Agree". After each round, the responses were calculated and the results included on subsequent rounds. 35 panelists from four pediatric trauma centers participated in the study, including 11 (31%) pediatric EM physicians, 8 (23%) pediatric trauma surgeons, 5 (14%) transfusionists, 5 (14%) pediatric anesthesiologists, and 6 (17%) pediatric critical care physicians (range of 8 to 10 from each clinical site). Four survey iterations were performed. In total 176 statements were rated and 39 were accepted by criteria across all 23 categories. An rational algorithm for transfusion in trauma was then developed. We successfully developed transfusion guidelines for various aspects of the management of children with hemorrhagic injuries using a modified Delphi process with broad interdisciplinary participation. We anticipate implementation of these guidelines will help minimize heterogeneity of transfusion practices across clinical sites for the upcoming clinical trial evaluating tranexamic acid in children with hemorrhage.

Impact of tranexamic acid use on blood loss and transfusion rates following femoral varus derotational osteotomy in children with cerebral palsy

PurposePrevious studies have established the safety and efficacy of tranexamic acid (TXA) in reducing blood loss after total joint arthroplasty and spinal fusion surgery; however, literature regarding the effectiveness of intraoperative TXA in children with cerebral palsy (CP) is limited. The aim of this study was to investigate the safety and efficacy of intraoperative TXA in reducing blood loss and transfusion requirements for children with CP undergoing a proximal femoral varus derotational osteotomy (VDRO).MethodsThis is a retrospective review of 258 children with CP who underwent VDRO performed at the author’s institution between 2004 and 2017. In all, 36 subjects underwent VDRO surgery with administration of intravenous TXA and 222 subjects underwent VDRO without administration of TXA. Outcome measures including blood loss, transfusion requirements and venous thromboembolic events were compared between groups using t-tests and chi-squared tests.ResultsNo significant differences were seen in the rates of transfusion between groups for the entire hospitalization (TXA group: 11.1% versus No TXA group: 19.8%), intraoperatively (TXA: 2.8% versus No TXA: 9.0%) or postoperatively (TXA: 8.3% versus No TXA: 14.4%). Intraoperative estimated blood loss (TXA: 144.4 mL versus No TXA: 159.0 mL) and percentage blood loss (TXA: 8.9% versus No TXA: 9.2%) were similar between groups. No major thromboembolic complications events occurred in either group.ConclusionThe use of TXA was not associated with thromboembolic complications in this series of children with CP undergoing VDRO surgery. Though there was a trend toward lower rates of intraoperative and postoperative blood transfusion with TXA use in these patients, the differences were not significant, possibly due to low estimated blood loss in both groups and sample size.Level of evidenceIII- retrospective comparative study

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial

BackgroundTrauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries.MethodsChildren with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15 mg/kg bolus dose over 20 min, followed by 2 mg/kg/hr infusion over 8 h), (2) TXA dose B (30 mg/kg bolus dose over 20 min, followed by 4 mg/kg/hr infusion over 8 h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48 h, intracranial hemorrhage progression at 24 h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures).DiscussionThis multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain.Trial registrationClinicalTrials.gov registration number: NCT02840097. Registered on 14 July 2016.

Pediatric neuroanesthesia

Pediatric neuroanesthesia is a fascinating, yet challenging branch of anesthesia. This review highlights some of the recent insights into pediatric neuroanesthesia from the past 18 months. Although there are incontrovertible evidences in animals suggesting that prolonged exposure to general anesthesia causes long-term neurological impairment, the translational relevance of these findings in humans is debatable. Early surgery for pediatric drug-refractory epilepsy is supported by emerging literature, but poses unique perioperative problems for the treating neuroanesthesiologist. Similarly, minimizing intraoperative blood loss and blood transfusion concerns every anesthesiologist managing small children. The usefulness of tranexamic acid in children is further enhanced by some studies in spine surgeries. Some pertinent issues related to intraoperative neuromonitoring are also discussed in the text. There are several logistical and ethical problems of carrying out high-quality prospective studies in children but important findings on prevention of anesthetic neurotoxicity; minimizing intraoperative blood loss, intraoperative neurophysiological monitoring, examining optimal doses and choices of anesthetic agents in epilepsy surgery have been published recently.

Safety and efficacy of tranexamic acid in bleeding paediatric trauma patients: a systematic review protocol

IntroductionTrauma is the leading cause of death among children aged 1–18. Studies indicate that better control of bleeding could potentially prevent 10–20% of trauma-related deaths. The antifibrinolytic agent tranexamic acid...

The Successful Use of Desmopressin With Tranexamic Acid in Children With Mild Type 1 Von Willebrand Disease Who Undergo Circumcision

Background: Desmopressin (DDAVP) is a synthetic vasopressin analog, and increases endogenous von Willebrand factor (VWF) by secreting it from the vascular endothelial cell. Circumcision is one of the oldest and most commonly performed operations in the world. This study reported the specific uses of DDAVP together with tranexamic acid in children with mild type 1 von Willebrand disease (VWD) undergoing circumcision. The aim of this study was to report the successful use of DDAVP in two doses and tranexamic acid in six children with VWD undergoing circumcision. Methods: Our study evaluated two doses of DDAVP therapy in circumcision operation of six male children diagnosed with mild type 1 VWD with a good response to DDAVP before they underwent circumcision, with a mean age of 7.3 years. The subcutaneous preparation of DDAVP was utilized. Under medical supervision, patients were subcutaneously injected DDAVP at a dose between 0.3 and 0.2 μg/kg based on their weight. Oral tranexamic acid was instituted at a dosage of 15 mg/kg three times per day for 5 days. The first dose was given 24 hours before circumcision. The first and second doses of DDAVP were given 1 hour before the circumcision and 24 hours after the circumcision, respectively. Results: This study included six male children aged 4 - 10 years with mild type 1 VWD, weighting 22 - 30 kg. The DDAVP dose (mean, range) based on the patient’s weight was 0.25 (0.23 - 0.28 μg/kg). The calculated dose was repeated two times for each patient. Laboratory values (mean, range, U/dL) of baseline VWF:Ag, VWF:RCo and FVIII:C in mild type 1 VWD patients were 37 (32 - 42), 38 (34 - 42), and 50 (44 - 56), respectively. Conclusion: Single infusions of DDAVP for common bleeding episodes do not usually require laboratory monitoring. There are limited published data to guide clinical practice about the optimal dosing and timing of these agents to prevent or resolve bleeding using DDAVP at minor surgeries as circumcision operation. Castaman et al showed almost all minor surgeries and deliveries occurring during follow-up were successfully managed with DDAVP in patients with type 1 VWD. We used two doses in circumcision like O’Brein. Comparison of the results across studies is difficult, as surgical techniques, timing, and frequency of DDAVP dosing, and use and dosing of antifibrinolytics all varied by institution. Two doses of DDAVP allowed adequate perioperative bleeding prophylaxis management in children with mild type 1 VWD who underwent circumcision surgery with presenting bleeding complications. Int J Clin Pediatr. 2015;4(4):181-183 doi: http://dx.doi.org/10.14740/ijcp228e

The Efficacy of Antifibrinolytic Drugs in Children Undergoing Noncardiac Surgery

Children undergoing major surgery are frequently exposed to a high risk of blood loss often requiring transfusion. Although the risks associated with blood product transfusion have considerably decreased over the last decade, transfusion is still associated with significant morbidity and mortality. Thus, rigorous efforts should be made to decrease surgical bleeding and the need for blood product transfusion. Antifibrinolytic drugs have been shown to be effective when used in both adult and pediatric surgical patients. While there are data in adults to support safety, data remain limited for pediatric patients. Since the restriction of aprotinin use in 2008, the most commonly used antifibrinolytic drugs have been the lysine analogs, tranexamic acid (TXA), and ε-aminocaproic acid, which inhibit the conversion of plasminogen to plasmin and decrease the degree of fibrinolysis. We performed a systematic review of the literature pertaining to the efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery. During spine surgery, both TXA and ε-aminocaproic acid decrease blood loss and transfusion requirements; however, this information comes from small, mainly retrospective trials. Two prospective, randomized, controlled trials have tested the efficacy of TXA in children undergoing craniofacial surgery and have reported that TXA decreases transfusion requirements. Two pharmacokinetic trials were also recently published and are summarized in this review. No data have been published regarding the efficacy of TXA administration in the pediatric trauma population. Further data are still needed in this field of study, and we discuss some perspectives for future research.

A Practical Tranexamic Acid Dosing Scheme Based on Population Pharmacokinetics in Children Undergoing Cardiac Surgery

Grassin-Delyle, Stansilas*; Couturier, Roland†; Abe, Emuri*; Alvarez, Jean Claude*; Devillier, Philippe*; Urien, Saik‡Author Information