Reversal of dabigatran by intraosseous or intravenous idarucizumab in a porcine polytrauma model

• Published in: British journal of anaesthesia : BJA Vol. 120; no. 5; pp. 978 - 987
• Main Authors: Akman, N., Braunschweig, T., Honickel, M., Schütt, K., Schöchl, H., Stoppe, C., Rossaint, R., Grottke, O.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2018
• Subjects: Administration, Intravenous; Animals; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - pharmacology; anticoagulants; Antithrombins; Blood Coagulation - drug effects; dabigatran; Dabigatran - antagonists & inhibitors; Disease Models, Animal; Hemorrhage - drug therapy; idarucizumab; Infusions, Intraosseous; intraosseous; Male; Multiple Trauma; Swine; thromboelastography; intraosseous; anticoagulants; idarucizumab; dabigatran; thromboelastography
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1016/j.bja.2018.01.027

Idarucizumab is licensed to reverse dabigatran in life-threatening haemorrhage. Establishment of venous access can be challenging, and the intraosseous (IO) route is a potentially life-saving alternative. In this study, we compared the efficacy and safety of IO or intravenous (i.v.) idarucizumab for dabigatran reversal in a porcine polytrauma model. Male pigs (n=21) received oral dabigatran etexilate (30 mg kg−1 bid) for 3 days. On the 4th day, animals received dabigatran infusion and were randomised 1:1:1 to receive IO saline (control), i.v. idarucizumab (60 mg kg−1), or IO idarucizumab (60 mg kg−1), or animals were included in a sham group (n=7). Study treatment was administered after polytrauma and the animals were monitored for 240 min, or until death. Coagulation status was monitored by thromboelastometry, thromboelastography, and thrombin measurements. Total blood loss was lowest in sham animals [521 (52) ml, P<0.01 vs all other groups], and comparable in the two idarucizumab groups [IO: 1085 (102) ml vs i.v.: 1142 (125) ml], and highest in the control group [4065 (557) ml, P<0.001 vs all other groups]. Survival to 240 min was 100% in the sham group and both idarucizumab groups, and 14% in the control group. IO and i.v. idarucizumab promptly normalised global coagulation assays and thrombin generation. Thromboelastography showed a strong correlation between dabigatran concentrations and R-time (R2=0.90 and 0.89) in idarucizumab-treated animals. Intravenous and intraosseous idarucizumab were comparable for reversing dabigatran in a porcine trauma model. Dabigatran reversal could be monitored using fully automated thromboelastography.