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HIGH VERSUS LOW PROTAMINE-TO-HEPARIN DOSING RATIO FOLLOWING CARDIOPULMONARY BYPASS: A MULTICENTER RANDOMIZED CONTROLLED TRIAL
Alexander Vonk, Michael Meesters.
VU University Medical Center, Amsterdam, Netherlands.

OBJECTIVE: Guidelines for perioperative blood management advise to dose protamine in a 1.0-1.3:1.0 ratio with heparin. However, due to the degrading and loss of heparin during surgery, protamine can be overdosed. Present study investigated whether the use of a lower protamine-to-heparin dosing ratio is superior to a high dosing ratio with respect to postoperative hemostasis.
METHODS: In this multicenter investigation, patients undergoing coronary artery bypass graft surgery were randomized into a low (0.8; n=46) or high protamine-to-heparin (1.3; n=36) dosing group based on total heparin administration. Patient hemostasis was monitored using rotational thromboelastometry before and 3 and 30 minutes after CPB.
RESULTS: CPB time estimated 89±29 vs. 90±36 minutes (P=0.92) in the low and high dosing groups. There were no differences in total heparin dosing (412±121 vs. 420±92 mg; P=0.75), while protamine administration was lower in the 0.8 (331±97 mg) than in the 1.3 group (545±120; P<0.001). ACT values following protamine administration were similar between groups. Clotting times for the INTEM (293±64 vs. 243±37 s; P<0.001) and HEPTEM (298±60 vs. 243±40 s; P<0.001) were prolonged at 3 minutes following protamine administration in the high dosing group, but were normalized 30 minutes later. Median 24-hour blood loss was increased in the high protamine dosing group.
CONCLUSIONS: A protamine-to-heparin dosing ratio of 1.3 is associated with a temporary prolongation of postoperative clotting times and increased blood loss when compared to a lower dosing strategy. Protamine overdosing should therefore be considered harmful for the restoration of perioperative hemostasis.


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