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CARDIOVASCULAR ANESTHESIOLOGY

Detection of Protamine and Heparin After Termination of Cardiopulmonary Bypass by Thrombelastometry (ROTEM®): Results of a Pilot Study

Markus Mittermayr, MD^*, Corinna Velik-Salchner, MD^*, Berndt Stalzer, MD^*, Josef Margreiter, MD^*, Anton Klingler, PhD, Werner Streif, MD, Dietmar Fries, MD^*, and Petra Innerhofer, MD^*

From the *Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria; Assign Data Management and Biostatistics GmbH, Innsbruck, Austria; and Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria.

Address correspondence and reprint requests to Markus Mittermayr, MD, Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Anichstr. 35, A-6020 Innsbruck, Austria. Address e-mail to markus.mittermayr{at}i-med.ac.at.

Abstract

BACKGROUND: Our goal of this study was to determine whether protamine’s effects on coagulation can be detected and differentiated from those of heparin when using thrombelastometry (ROTEM®).

METHODS: To reverse the effects of heparin after cardiopulmonary bypass (CPB), 22 consecutive patients undergoing aortocoronary bypass graft surgery were included. According to clinical routine, all patients received a first dose of protamine calculated from the total amount of heparin given; additional protamine (70 U/kg) was administered to patients with activated clotting time (ACT) above baseline and clinical signs of diffuse bleeding. Simultaneously, routine ACT measurements, ROTEM assays (heparin-sensitive INTEM, and heparinase-containing HEPTEM test) and standard coagulation tests were performed, and the activity of coagulation factors as well as antifactor Xa activity measured.

RESULTS: Administration of additional protamine (n = 16) resulted in a statistically significant increase in coagulation times on the intrinsically activated test (INTEM-CT), namely from (mean [±sd]) 219.8 (±19.1) s to 241.1 (±21.7) s (P < 0.001), and on the heparinase-containing test (HEPTEM-CT), namely from 210.2 (±19.9) s to 226.8 (±21.8) s (P < 0.001). These changes were not observed in patients receiving a single protamine dose (n = 6). The INTEM-CT:HEPTEM-CT ratio correctly identified 56 of the 58 samples as not containing residual heparin and correctly detected residual heparin in 3 of the only 6 samples showing elevated antifactor Xa values after CPB.

CONCLUSION: Our preliminary data show that at termination of CPB administration of additional protamine results in a brief prolongation of coagulation times on the INTEM and HEPTEM test and that ROTEM might be useful in excluding residual heparin in cases showing prolonged ACT.

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