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...

This TXA pharmacokinetic analysis is reported for the first time in neonates and young children undergoing complex cardiac surgeries with cardiopulmonary bypass. Dosing recommendations are provided as guidance for maintaining desired target concentrations.

Physiological disturbances induced by cardiopulmonary bypass (CPB) and hypothermia during cardiac surgery are particularly pronounced in certain unique patient populations, such as patients with sickle cell disease (SCD) and cold agglutinin disease. Red blood cells containing hemoglobin S (HbS) are at increased risk of sickling under conditions encountered during cardiac surgery, leading to SCD-related complications such as vaso-occlusive events. While a target level of HbS has not been determined for patients with SCD undergoing CPB, a safe practice includes increasing the Hb level to 10 g/dL and reducing the proportion of HbS to approximately 30%. This can be accomplished through simple or exchange transfusion prior to surgery or via the modification of the CPB circuit prime. There is no clear consensus on the formulation or the delivery temperature of the cardioplegia solution necessary to prevent sickling and microvascular occlusion. The presence of cold agglutinins is another entity requiring extra vigilance for the conduct of CPB, where hypothermia can lead to activation of cold agglutinins inducing massive hemagglutination, hemolysis, microvascular thrombosis, and possibly intracoronary thrombosis. Determination of thermal amplitude is important to provide a safe reference range of temperature during surgery. High-volume plasmapheresis may be warranted to reduce cold agglutinin titers. Both warm blood cardioplegia and cold crystalloid cardioplegia above the thermal amplitude have been utilized with success.

Background: Some patients with hypoplastic left heart syndrome (HLHS) and HLHS-related malformations with ductal-dependent systemic circulation are extremely high-risk for Norwood palliation. We report our comprehensive approach to the management of these patients designed to maximize survival and optimize the utilization of donor hearts. Methods: We reviewed our entire current single center experience with 83 neonates and infants with HLHS and HLHS-related malformations (2015-2021). Standard-risk patients (n = 62) underwent initial Norwood (Stage 1) palliation. High-risk patients with risk factors other than major cardiac risk factors (n = 9) underwent initial Hybrid Stage 1 palliation, consisting of application of bilateral pulmonary bands, stent placement in the patent arterial duct, and atrial septectomy if needed. High-risk patients with major cardiac risk factors (n = 9) were bridged to transplantation with initial combined Hybrid Stage 1 palliation and pulsatile ventricular assist device (VAD) insertion (HYBRID + VAD). Three patients were bridged to transplantation with prostaglandin. Results: Overall survival at 1 year = 90.4% (75/83). Operative Mortality for standard-risk patients undergoing initial Norwood (Stage 1) Operation was 2/62 (3.2%). Of 60 survivors: 57 underwent Glenn, 2 underwent biventricular repair, and 1 underwent cardiac transplantation. Operative Mortality for high-risk patients with risk factors other than major cardiac risk factors undergoing initial Hybrid Stage 1 palliation without VAD was 0/9: 4 underwent transplantation, 1 awaits transplantation, 3 underwent Comprehensive Stage 2 (with 1 death), and 1 underwent biventricular repair. Of 9 HYBRID + VAD patients, 6 (67%) underwent successful cardiac transplantation and are alive today and 3 (33%) died while awaiting transplantation on VAD. Median length of VAD support was 134 days (mean = 134, range = 56-226). Conclusion: A comprehensive approach to the management of patients with HLHS or HLHS-related malformations is associated with Operative Mortality after Norwood of 2/62 = 3.2% and a one-year survival of 75/83 = 90.4%. A subset of 9/83 patients (11%) were stabilized with HYBRID + VAD while awaiting transplantation. VAD facilitates survival on the waiting list during prolonged wait times.

Therapeutic blood concentrations of milrinone exhibit a significant inhibitory effect on ADP and AA-induced platelet activation as determined by TEG Platelet Mapping, without affecting the conventional kaolin-activated TEG. We suggest that TEG Platelet Mapping results be interpreted with caution in patients being treated with milrinone, and other drugs that modify platelet cyclic nucleotide concentrations.

Objectives: Shunt thrombosis, a potential complication of aortopulmonary shunting, is associated with high mortality. Commonly used oral antiplatelet drugs such as aspirin demonstrate variable absorption and inconsistent antiplatelet effect in critically ill patients early after surgery. IV glycoprotein IIb/IIIa inhibitors are antiplatelet agents with rapid and reproducible effect that may be beneficial as a bridge to oral therapy. Design: Retrospective review of pediatric patients undergoing treatment with IV tirofiban. Discarded blood samples were used to determine pharmacokinetic parameters. Setting: Pediatric cardiac ICU at a single institution. Patients: Fifty-two pediatric patients (< 18 yr) undergoing surgical aortopulmonary shunt procedure who received tirofiban infusion as a bridge to oral aspirin. Interventions: None. Measurements and Main Results: Primary outcome measures were shunt thrombosis and bleeding events, whereas secondary outcomes included measurement of platelet inhibition by thromboelastography with platelet mapping and pharmacokinetic analysis (performed in a subset of 15 patients). Shunt thrombosis occurred in two of 52 patients (3.9%) after prophylaxis treatment with tirofiban; both thrombosis events occurred after discontinuation of the drug. One patient (1.9%) experienced bleeding complication during the infusion. A tirofiban bolus of 10 µg/kg and infusion of 0.15 µg/kg/min resulted in significantly increased platelet inhibition via adenosine diphosphate pathway (median 66% [43–96] pre-tirofiban compared with 97% [92–99%] at 2 hr; p < 0.05). Half-life of tirofiban in plasma was 142 ± 1.5 minutes, and the average steady-state concentration was 112 ± 62 ng/mL. Age and serum creatinine were significant covariates associated with systemic clearance. Dosing simulations were generated based upon one compartment model. Conclusions: IV glycoprotein IIb/IIIa inhibitor as a bridge to oral antiplatelet therapy is safe in pediatric patients after aortopulmonary shunting. Dosing considerations should include both age and renal function. Randomized trials are warranted to establish efficacy compared with current anticoagulation practices.

Neonates and infants undergoing cardiac surgery with cardiopulmonary bypass are exposed to multiple blood products from different donors. The volume of the bypass circuit is often as large as the patient's total blood volume and asanguineous bypass primes are unusual. As a result, blood products are required for the cardiopulmonary bypass prime and are often used to treat the postbypass dilutional coagulopathy. We review clot formation and strength, cardiopulmonary bypass prime considerations, assessment of postbypass coagulopathy, component therapy use, ultrafiltration techniques, and use of antifibrinolytic medications. A combined approach including techniques to minimize the prime volume, utilization of ultrafiltration, administration of antifibrinolytics during surgery, and the proper treatment of the dilutional coagulopathy can limit the transfusion requirements.

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