Protamine dosage based on two titrations reduces blood loss after valve replacement surgery: a prospective, double-blinded, randomized study.
BACKGROUND
Postoperative hemorrhage following cardiopulmonary bypass in heart valve replacement patients may be caused by a mismatch of protamine and heparin. We hypothesized that a 2-titration-guided protamine dose would reduce protamine-heparin mismatch and bleeding in those patients.


METHODS
Patients scheduled for elective cardiac valve replacement surgery (N = 60) were randomly divided into 3 groups. All patients received 2 titrations: the first at termination of cardiopulmonary bypass and the second at 5 minutes after the initial dose of protamine. In the control group, the initial protamine dose was based on the heparin dose received; the supplemental protamine dose was empirically determined. In the single-titration group, the initial dose was based on the first titration, while supplemental dose was empirically determined. In the 2-titration group, both initial and supplemental doses were based on titrations. Bleeding volumes were recorded from the time of first protamine dose to 24 hours after surgery.


RESULTS
Most patients needed supplemental protamine according to second titrations. In the 2-titration group, 12 patients received supplemental protamine, whereas only 1 patient in the single-titration group and 6 in the control group received supplemental protamine (P = 0.003). The blood loss was significantly less in the 2-titration group (526 ± 131 mL) than in the control group (730 ± 385 mL; P = 0.019).


CONCLUSIONS
A higher dosage of protamine based on 2 titrations reduced blood loss after surgery, supporting the hypothesis that inadequate dosage of protamine contributes to hemorrhage after valve replacement surgery.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu City, China.
Yan
Y
Guo
Jiali
J
Tang
Lei
L
Du
Jin
J
Liu
Raphael C
RC
Liu
Xiang
X
Liu
Yingqiang
Y
Guo
D000328:Adult; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods; D016009:Chi-Square Distribution; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects* / Q000379:methods; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006494:Heparin Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000188:drug therapy / Q000517:prevention & control*; D011446:Prospective Studies; D011479:Protamines / Q000008:administration & dosage*; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome
D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin