Factors affecting heparin rebound and methods of re-neutralization

Wand S., Heise D., Hillmann N., Bireta C., Bräuer A., Ahsen N.V., Quintel M.

Identifying the cause of a bleeding complication after cardiac surgery can be crucial. This study sought to clarify whether the application of unprocessed autologous pump blood influences anti-factor Xa activity after cardiac surgery and evaluated 2 point-of-care methods regarding their ability to identify an elevated anti-factor Xa activity at different timepoints after cardiopulmonary bypass. Anti-factor Xa activity, heparin/protamine titration and the clotting time ratio of thromboelastometry in the INTEM and HEPTEM were measured at baseline (T1), after the application of protamine (T2) and after the complete application of autologous pump blood (T3). Anti-factor Xa activity decreased significantly between T2 and T3 as well did the absolute number of patients with an elevated anti-factor Xa activity. Receiver Operating Curve analyses were performed for both point-of-care methods. At T2 neither could identify patients with an elevated anti-factor Xa activity, while both methods were able to do so at T3 with high sensitivity and specificity. This difference suggests that an interference in the detection of residual heparinization with point-of-care methods exists right after the application of protamine, which seems to subside after a short time span. Nevertheless, results of point-of-care testing for residual heparinization after cardiopulmonary bypass need to be interpreted considering the protamine-heparin ratio and the timepoint of protamine administration.

OGAWA S.

Meesters M.I., Veerhoek D., de Lange F., de Vries J., de Jong J.R., Romijn J.W., Kelchtermans H., Huskens D., van der Steeg R., Thomas P.W., Burtman D.T., van Barneveld L.J., Vonk A.B., Boer C.

SummaryWhile experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open-label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. The primary outcome was 24-hour blood loss. Patient haemostasis was monitored using rotational thromboelastometry and a thrombin generation assay. The low protamine-to-heparin dosing ratio group received less protamine (329 ± 95 vs 539 ± 117 mg; p<0.001), while post-protamine activated clotting times were similar among groups. The high dosing group revealed increased intrinsic clotting times (236 ± 74 vs 196 ± 64 s; p=0.006) and the maximum post-protamine thrombin generation was less suppressed in the low dosing group (38 ± 40% vs 6 ± 9%; p=0.001). Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95% CI 500–830 ml vs 470 ml; 95% CI 420–530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11% vs 0%; p=0.02) and platelet concentrate (21% vs 6%; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery.

AbstractThe American Society of Anesthesiologists Committee on Standards and Practice Parameters and the Task Force on Perioperative Blood Management presents an updated report of the Practice Guidelines for Perioperative Blood Management.Supplemental Digital Content is available in the text.

Ichikawa J., Kodaka M., Nishiyama K., Hirasaki Y., Ozaki M., Komori M.

Kozek-Langenecker S.A., Afshari A., Albaladejo P., Santullano C.A., De Robertis E., Filipescu D.C., Fries D., Görlinger K., Haas T., Imberger G., Jacob M., Lancé M., Llau J., Mallett S., Meier J., et. al.

The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient's tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

Gravlee G., Rogers A., Dudas L., Taylor R., Roy R., Case L. ., Triscott M., Brown C., Mark L., Cordell A. .

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) greater than 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration greater than 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of beta thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 +/- 4,800 U for group A and 57,000 +/- 10,700 U for group H (P less than 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage +/- SD = 901 +/- 414 ml in group A, 1035 +/- 501 ml in group H), nor did the incidence of transfusion with homologous blood products.(ABSTRACT TRUNCATED AT 250 WORDS)