bivalirudin and Heart-Defects--Congenital

To determine the safety and efficacy of bivalirudin as an anticoagulant for pediatric open heart surgery (OHS) and to determine its appropriate dosage for this purpose.. Prospective, randomized controlled trial.. Tertiary care hospital.. Fifty acyanotic children aged 1-12 years undergoing OHS.. The children were randomized to receive either 4 mg/kg of heparin (n = 25, group H) or 1 mg/kg of bivalirudin bolus followed by 2.5 mg/kg/h infusion (n = 25, group B) as the anticoagulant. The doses were adjusted to maintain activated clotting time (ACT) above 480 seconds. At the conclusion of surgery, protamine (1.3 mg/100 U of heparin) was administered to children in group H.. The children were comparable in both groups with regard to demographic characteristics. The mean age and weight were 51.5 months and 13.4 kg in group H, and 59.3 months and 13.4 kg in group B. The dose of anticoagulant required was 4.0 ± 0.2 mg/kg in group H and 1.7 ± 0.2 mg/kg followed by 3.0 ± 0.7 mg/kg/h infusion in group B (p < 0.001). One child in group H required an additional dose compared to 13 (54.2%) children in group B. Intraoperatively, the ACT achieved was higher in group H compared to group B (p < 0.05). The ACT returned to baseline value after protamine administration in group H, but it remained elevated for 2 hours after termination of cardiopulmonary bypass (CPB) in group B (p < 0.01). The ACT was higher in group B compared to group H for 6 hours after termination of CPB (p < 0.05). Heparin prolonged the onset of clotting, decreased the rate and strength of thrombus formation, and inhibited platelet function to a greater extent than bivalirudin on viscoelastic coagulation testing. The total duration of surgery was prolonged in group B. The postoperative chest tube drainage was similar in group B (4.9 mL/kg) as in group H (5.9 mL/kg) in spite of higher ACT. The transfusion requirements were similar. No adverse event occurred in any patient.. Bivalirudin is a safe and effective anticoagulant for pediatric OHS. Though it is not suitable as a routine anticoagulant for this purpose, it may be used as a heparin alternative in instances when heparin cannot be used. The dose required to maintain ACT for more than 480 seconds was 1.7 ± 0.2 mg/kg followed by 3.0 ± 0.7 mg/kg/h infusion. The ACT remained elevated for 2 hours after stopping the infusion. Bivalirudin did not increase postoperative bleeding and transfusion requirement.

Topics: Anticoagulants; Cardiopulmonary Bypass; Child; Child, Preschool; Female; Heart Defects, Congenital; Heparin; Hirudins; Humans; Infant; Male; Peptide Fragments; Prospective Studies; Recombinant Proteins

Pediatric physicians regularly face the problem of uncertain procedural anticoagulation in children, especially in neonates. We sought to evaluate the safety, plasma concentration (pharmacokinetics, PK), pharmacodynamics (PD), and dosing guidelines of bivalirudin when used as a procedural anticoagulant in pediatric percutaneous intravascular procedures.. Pediatric subjects undergoing percutaneous intravascular procedures for congenital heart disease were enrolled and received the current weight-based dose used in percutaneous coronary interventions (0.75 mg/kg bolus, 1.75 mg/kg/hr infusion). Blood samples for PK/PD analyses were drawn, and safety was evaluated by monitoring bleeding and thrombosis events. A total of 110 patients (11 neonates, 33 infants, 32 young children, and 34 older children) were enrolled; 106 patients received the protocol dose. The PK/PD response of bivalirudin was predictable and behaved in a manner similar to that in adults. Weight-normalized bivalirudin clearance rates were more rapid in neonates and decreased with increasing age. Bivalirudin concentrations were slightly lower in neonates, with a trend to an increase with age. Activating clotting time response was consistent with adult studies and prolonged in all age groups, and there was reasonable correlation between activating clotting time and bivalirudin plasma concentrations across all age groups. There were few major bleeding (2 of 110, 1.8%) or thrombotic events (9 of 110, 8.2%) reported.. PK/PD response of bivalirudin in the pediatric population is predictable and behaves in a manner similar to that in adults. Using adult dosing, bivalirudin safely provided the expected anticoagulant effect in the pediatric population undergoing intravascular procedures for congenital heart disease.

Topics: Adolescent; Age Factors; Anticoagulants; Cardiac Catheterization; Child; Child, Preschool; Female; Heart Defects, Congenital; Hemorrhage; Hirudins; Humans; Infant; Infant, Newborn; Male; Peptide Fragments; Prospective Studies; Recombinant Proteins; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; United States

To determine the dosage of bivalirudin as the anticoagulant for cardiac surgery in neonates and infants.. Pilot study.. Tertiary-care hospital.. Twenty-five neonates and infants with congenital heart disease (CHD) undergoing cardiac surgery.. The children received a 1 mg/kg bivalirudin bolus followed by a 2.5 mg/kg/h infusion as the anticoagulant for cardiac surgery. The dose was adjusted subsequently to maintain an activated clotting time (ACT) >480 s.. The mean age and weight were 5.3 months and 5.2 kg, respectively. Out of the 25 children, 16 were cyanotic. Baseline rotational thromboelastometry (ROTEM) (Tem Innovations GmbH, Munich, Germany) analysis revealed an underlying coagulation defect across EXTEM, INTEM, FIBTEM, and ADPTEM parameters. The dose of anticoagulant required was 1 mg/kg, followed by a 2.2 ± 0.4 mg/kg/h infusion. Only 1 child required an additional bolus dose. The ACT remained elevated for 4 hours after discontinuation of infusion. The mean 24-h postoperative chest tube drainage was 92 ± 36 mL. Excessive bleeding occurred in 4 children, 1 of whom required re-exploration. The platelet count remained low for 5 days, and, postoperatively, the prothrombin time and activated partial thromboplastin time remained low for 2 days.. Effective anticoagulation was achieved with bivalirudin in the neonates and infants undergoing cardiac surgery. The dose required to maintain an ACT >480 s was 1.0 mg/kg, followed by 2.2 ± 0.4 mg/kg/h. The ACT remained elevated for 4 h after the discontinuation of bivalirudin infusion, resulting in an increased chest-tube output in some patients. Randomized, controlled trials are needed to further evaluate the safety of bivalirudin in the neonates and infants with complex congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass.

Topics: Anticoagulants; Cardiac Surgical Procedures; Heart Defects, Congenital; Hirudins; Humans; Infant; Infant, Newborn; Peptide Fragments; Pilot Projects; Recombinant Proteins

Thromboembolic events while receiving ventricular assist device (VAD) support remain a significant cause of morbidity and mortality despite standard anti-coagulation and anti-platelet therapies. The use of bivalirudin and epoprostenol infusions as an alternate anti-thrombotic (AT) regimen in pediatric VAD patients was reviewed.. This was a retrospective record review of 6 pediatric patients (aged ≤17 years) at 2 institutions treated with bivalirudin and epoprostenol infusions while being supported with the Berlin Heart EXCOR (Berlin Heart GmbH, Berlin, Germany) VAD.. Six patients (age, 0.8-14 years; weight, 6.7-29.7 kg) were treated. Diagnoses included cardiomyopathy in 2 and congenital heart disease in 4. VAD support was left VAD in 2 and bi-VAD in 4, with duration of support of 21 to 155 days. Three patients required extracorporeal membrane oxygenation before VAD support. Bivalirudin/epoprostenol was used after recurrent thromboses on conventional medication in 3 patients, heparin-induced thrombocytopenia in 2, and in 1 patient considered high risk with a prosthetic mitral valve. The bivalirudin dose was titrated to partial thromboplastin time (PTT) of 1.5- to 2-times baseline (0.1-0.8 mg/kg/hour); the epoprostenol dose was 2 to 10 ng/kg/min. Additional anti-platelet agents included acetylsalicylic acid, dipyridamole, and clopidogrel in 5 patients each. No bleeding complications occurred. One patient sustained a cerebrovascular infarct on therapy, with subsequent complete recovery. No other complications occurred. Five patients underwent successful transplantation, and 1 patient died of multisystem organ failure.. This report provides data on estimated safety and efficacy of bivalirudin and epoprostenol as an AT strategy in pediatric patients on extended VAD support. The short drug half-life and predictable AT response facilitated conversion to standard AT regimens at the time of transplantation (heparin-induced thrombocytopenia-negative patients). These agents should be considered for management of pediatric VAD patients when standard regimens fail.

Topics: Adolescent; Cardiomyopathies; Child; Child, Preschool; Disease Management; Dose-Response Relationship, Drug; Epoprostenol; Fibrinolytic Agents; Heart Defects, Congenital; Heart-Assist Devices; Hirudins; Humans; Infant; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thromboembolism; Treatment Outcome

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening, adverse effect of heparin therapy. Patients with this complication require an alternative approach to anticoagulation. Bivalirudin is a direct thrombin inhibitor with an efficacy comparable to that of heparin, a short half-life, and reduced bleeding complications in adults. We present the case of a 2-year-old boy with HIT Type II who underwent recanalization of an occluded superior vena cava and stent placement, utilizing bivalirudin as anticoagulant.

Topics: Angioplasty, Balloon; Anticoagulants; Child, Preschool; Heart Defects, Congenital; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Recurrence; Stents; Superior Vena Cava Syndrome; Thrombocytopenia