Randomized Controlled Trial of Heparin Versus Bivalirudin Anticoagulation in Acyanotic Children Undergoing Open Heart Surgery
RCT published in J Cardiothorac Vasc Anesth (2018)
Abstract
OBJECTIVE: 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. DESIGN: Prospective, randomized controlled trial. SETTING: Tertiary care hospital. PARTICIPANTS: Fifty acyanotic children aged 1-12 years undergoing OHS. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSION: 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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
RCT in 50 acyanotic children (1-12 yr) showed bivalirudin (1.7 mg/kg bolus, 3.0 mg/kg/h) safe and effective for OHS without increasing bleeding/transfusion versus heparin.
Why This Matters for Hirudotherapy
This randomized controlled trial compared heparin versus bivalirudin — a synthetic direct thrombin inhibitor structurally modeled on hirudin, the principal anticoagulant of medicinal leech saliva — for anticoagulation in 50 acyanotic children aged 1–12 years undergoing open heart surgery. The study found bivalirudin to be safe and effective, with similar postoperative chest tube drainage and transfusion requirements compared to heparin and no adverse events, though more children in the bivalirudin group required additional dosing and total surgery duration was prolonged. For ASH, this trial provides valuable clinical evidence on how a hirudin-inspired agent performs in a high-acuity surgical setting, directly relevant to the pharmacological legacy of the leech secretome. The key caveat is that this was a relatively small single-center pediatric study of a pharmaceutical bivalirudin preparation rather than leech therapy itself, and the authors concluded bivalirudin is not suitable as a routine anticoagulant for this application.
Citation
Randomized Controlled Trial of Heparin Versus Bivalirudin Anticoagulation in Acyanotic Children Undergoing Open Heart Surgery.
Hasija S et al. · Journal of cardiothoracic and vascular anesthesia, 2018
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