TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.
We have developed an injectable foam suspension containing self-assembling, lipid-based microparticles encapsulating a core of pure oxygen gas for intravenous injection. Prototype suspensions were manufactured to contain between 50 and 90 ml of oxygen gas per deciliter of suspension. Particle size was polydisperse, with a mean particle diameter between 2 and 4 μm. When mixed with human blood ex vivo, oxygen transfer from 70 volume % microparticles was complete within 4 s. When the microparticles were infused by intravenous injection into hypoxemic rabbits, arterial saturations increased within seconds to near-normal levels; this was followed by a decrease in oxygen tensions after stopping the infusions. The particles were also infused into rabbits undergoing 15 min of complete tracheal occlusion. Oxygen microparticles significantly decreased the degree of hypoxemia in these rabbits, and the incidence of cardiac arrest and organ injury was reduced compared to controls. The ability to administer oxygen and other gases directly to the bloodstream may represent a technique for short-term rescue of profoundly hypoxemic patients, to selectively augment oxygen delivery to at-risk organs, or for novel diagnostic techniques. Furthermore, the ability to titrate gas infusions rapidly may minimize oxygen-related toxicity.
C raniosynostosis, or premature closure of the skull sutures, is a relatively common disorder that is treated by expanding and remodeling of the cranium in early infancy to prevent increased intracranial pressure, cerebral compression, and blindness. The surgery results in considerable blood loss and transfusion-related morbidity and mortality. Tranexamic acid (TXA) is used to reduce perioperative blood loss in many settings, but data on its efficacy in children are limited. This prospective, randomized, double-blind, placebo-controlled, parallel trial evaluated the efficacy of a dose regimen of TXA to reduce blood loss and transfusion in 43 children undergoing surgery for craniosynostosis reconstruction.Patients, aged 2 months to 6 years, received either intravenous (IV) TXA (n = 23) or 0.9% saline (n = 20). The loading dose of TXA was 50 mg/kg diluted in saline to a volume of 1 mL/kg administered as an infusion of 15 minutes, followed immediately by an infusion of 5 mg/kg per hour. Patients in the placebo group received 1 mL/kg 0.9% saline over 15 minutes followed immediately by an infusion of 0.1 mL/kg per hour. Anesthetic management was standardized with sevoflurane, nitrous oxide, and oxygen for inhalation induction followed by IV administration of vecuronium and maintenance with sevoflurane. Sufentanil was administered before incision followed by an IV infusion (0.1Y0.5 Kg/kg per hour). Fluid therapy and blood loss were managed with crystalloid solutions, human albumin (5%), and blood products, at the discretion of the anesthesiologist. Coagulation blood parameters were measured preoperatively, intraoperatively after the estimated loss of about 1 blood volume, and postoperatively. Tranexamic acid plasma concentrations were measured throughout the surgery.Demographic and baseline characteristics of the 2 groups were similar. The mean total blood loss in the TXA group was 65 mL/kg compared with 119 mL/kg in the placebo group. Median intraoperative blood losses were 62 and 101 mL/kg, and mean postoperative losses were 3 and 12 mL/kg, respectively. All patients in both groups received blood transfusions. The volume of packed red blood cells (PRBCs) transfused intraoperatively was 33 mL/kg in the TXA group and 48 mL/kg in the placebo group, a statistically significant difference. The PRBC volume transfused within 24 hours after surgery was a median of 0 and 5 mL/kg in the TXA and placebo groups, respectively. The mean difference between the 2 groups for PRBCs transfused was 23 mL/kg. The median number of units of PRBCs transfused intraoperatively was 1 for the TXA group and 2 for the placebo group. Within 24 hours after surgery, the medians were 0 and 1 unit. Both of these were statistically significantly different. Postoperative transfusions were required in 50% of the patients in the placebo group but none in the TXA group. More patients in the placebo group than in the TXA group required intraoperative fresh frozen plasma. No patients in the TXA arm of the study had any complications. One patient in the place...
T ranexamic acid (TXA) is often used to reduce blood loss and need for transfusion in children undergoing cardiac surgery. However, analysis of TXA in young children who need cardiac surgery that includes cardiopulmonary bypass (CPB), hypothermia, circulatory arrest, and ultrafiltration has not been conducted.The present study included 55 pediatric patients separated into 3 groups: children younger than 2 months, infants 2 months to 1 year old, and children older than 1 year and weighing up to 20 kg. Tranexamic acid was administered at 100 mg/kg followed by a 10 mg/kg per hour throughout the surgery, and a dose of 100 mg/kg was placed in the CPB prime. High-performance liquid chromatography was used to measure concentrations of TXA in the blood. Results of the first examination of TXA in young pediatric patients provide dose guidelines for use of TXA. A safe and effective TXA concentration range for young cardiac surgery patients needs to be better defined. COMMENTAlthough the use of antifibrinolytics to prevent bleeding after CPB is well established, there are scant data on TXA in neonates and young infants undergoing complex cardiac operations. Drug disposition pharmacokinetics in neonatal populations is often substantially altered because of immature organ development with liver metabolism, biliary conjugation, and renal excretion taking months and sometimes years to fully develop. For this reason, the covariate age better predicts drug pharmacokinetics than body weight because of age-related organ and enzyme system development. Here, Wesley et al publish the first comprehensive pharmacokinetic investigation of TXA in neonates, young infants, and children undergoing complex cardiac surgery. The authors find that age is a much better covariate than body weight and that in neonates and young infants, interestingly, the bolus dose of TXA required to maintain a given plasma level decreases with age. Although CPB alters the disposition pharmacokinetics of TXA in children, the use of modified ultrafiltrate had no impact on TXA concentrations. Instead, patient age was the dominant factor in predicting TXA pharmacokinetics. That is, older children required lower doses.Wesley et al recruited 55 pediatric patients undergoing openheart surgery and divided them into 3 groups; children younger than 2 months, infants 2 months to 1 year, and children older than 1 year weighing up to 20 kg. Tranexamic acid 100 mg/kg was administered after anesthetic induction followed by 10 mg/kg per hour, and an additional 100 mg/kg was added to the CPB prime. A total of 889 concentration-time observations were obtained from these 55 patients, and CBP bypass management included ultrafiltration in all patients, modified ultrafiltration in select cases, and circulatory arrest in a few cases. Temperature on CPB ranged from 17.4°C to 34°C, with a median temperature of 28.1°C. Pharmacokinetic analysis was performed using a 2-compartment model and NONMEM (nonlinear mixed-effects model), with age being the most relevant covariate. Although the opti...
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