Robust K-PD model for activated clotting time prediction and UFH dose individualisation during cardiopulmonary bypass

Background: A critical aspect of cardiopulmonary bypass (CPB) is to achieve full anticoagulation to prevent thrombosis and consumptive coagulation without using excessive amount of heparin. This can be achieved with heparin dose response (HDR) test in vitro to calculate an individualized heparin bolus to reach a target activated clotting time (ACT) and heparin concentration. However, we often observe that the measured ACT (mACT) with the calculated heparin bolus gives significant errors, both positive (mACT is higher than expected) and negative (mACT is lower), from expected ACT (eACT). Methods: We performed a retrospective study of 250 patients who underwent cardiac surgery to attain an error distribution of the mACT from eACT with calculated heparin bolus. In addition, it is aimed to identify possible patterns of baseline ACT (bACT), calculated heparin concentration (CHC) and HDR slope that are associated with the significant positive and negative errors. Results: We found that individualized heparin bolus by HDR test is consistently underestimated while it gave a significant number of positive and negative errors. Further analysis indicates that significant negative errors correlate with high bACT and slope and low CHC while significant positive errors with low bACT and slope and high CHC. Conclusion: The mACT can be substantially different from eACT. The accuracy of the HDR test appears to be dependent upon bACT, slope, and CHC. Based on our analysis, we provide several recommendations and a flow chart to improve the quality of individualized heparin management on CPB.

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Extrinsic Pathway-Associated Activated Clotting Time for Anticoagulation Monitoring During Cardiopulmonary Bypass

Anesthesia & Analgesia ◽

10.1097/00000539-199608000-00043 ◽

1996 ◽

Vol 83 (2) ◽

pp. 433

Author(s):

Y. J. Gu ◽

R. J. Huyzen ◽

W. van Oeveren

Keyword(s):

Cardiopulmonary Bypass ◽

Clotting Time ◽

Extrinsic Pathway ◽

Activated Clotting Time

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Complement consumption during cardiopulmonary bypass: comparison of Duraflo II heparin-coated and uncoated circuits in fully heparinized patients

Perfusion ◽

10.1177/026765919601100406 ◽

1996 ◽

Vol 11 (4) ◽

pp. 333-337 ◽

Cited By ~ 5

Author(s):

Ahmet Hamulu ◽

Berent Discigil ◽

Mustafa Özbaran ◽

Tanzer Çalkavur ◽

Erkan Kara ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Postoperative Period ◽

Extracorporeal Circulation ◽

Myocardial Revascularization ◽

Control Group ◽

Clotting Time ◽

Normal Range ◽

Activated Clotting Time ◽

Systemic Heparinization

Heparin attachment to synthetic surfaces is one means of improving the biocompatibility of clinically used cardiopulmonary bypass (CPB) circuits. To assess the effect of heparin-coated circuits on complement consumption during CPB, 40 patients undergoing elective myocardial revascularization were prospectively randomized either to a group in which a completely Duraflo II heparin-coated circuit was used for perfusion (heparin-coated Group, n = 20 patients) or to a control group (n = 20 patients) in which an uncoated, but otherwise standard circuit was used. Full systemic heparinization was induced (activated clotting time, 480 seconds) in all the patients included in the study, regardless of which perfusion circuit was used. The two groups did not differ significantly in terms of bodyweight, aortic crossclamp and extracorporeal circulation times. No patient had difficulty in weaning from bypass and the postoperative period was uneventful in all patients. Concentrations of C3 and C4 were found to be within the 'normal' range in the prebypass period in both groups. There were no significant intergroup differences with regard to C3 and C4 consumption during CPB. We conclude that Duraflo II heparin- coated circuits have no effect in reducing complement consumption during CPB in fully heparinized patients.

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Anticoagulation in Cardiopulmonary Bypass

10.1055/s-0039-1680714 ◽

1977 ◽

Author(s):

C. Thomas Kisker ◽

John A. Young ◽

Donald B. Doty ◽

Barbara J. Taylor

Keyword(s):

Cardiopulmonary Bypass ◽

Antithrombin Iii ◽

Human Subjects ◽

Mean Value ◽

Clotting Time ◽

Excessive Bleeding ◽

Safe Level ◽

Activated Clotting Time ◽

Before And After ◽

The Mean

Prolonging the activated clotting time (ACT) 2 to 3 times normal is said to provide a “safe” level of anticoagulation during cardiopulmonary bypass. To test this level of anticoagulation 9 monkeys were anticoagulated with heparin at the start of cardiopulmonary bypass so that ACT’s ranged from 201 sec to > 1000 sec (normal 91 sec). ACT, platelet count (P), fibrinogen (F), and fibrin monomer (FM) were measured at 10, 30, 60, 90, and 120 minutes during bypass. Antithrombin III (AT3) was measured before and after bypass. Six monkeys developed increased FM indicating active coagulation beginning from 10 to 60 minutes on bypass. ACT’s were > 200 sec in all animals at the time of FM detection. P fell below 100,000/mm3 in the 6 animals with elevated FM, but remained above 100,000/mm3 in the other 3 animals. The mean value of AT3 (69%) decreased to 24.4% after bypass in the 6 animals with elevated FM, but was 61% after bypass in the others. Scanning electron microscopy of the oxygenator membranes showed significant amounts of fibrin on the membranes used in monkeys who developed increased FM levels, but not on those with normal FM concentrations. F decreased from 167 mgm/dl to 80.5 mgm/dl in monkeys with elevated FM and to 117 mgm/dl in those with normal FM concentrations. Excessive bleeding did not occur in the animals without increased FM although ACT’s were in excess of 1000 sec. Subsequently three human subjects on cardiopulmonary bypass whose ACT’s were maintained above 400 sec have not shown increased FM levels. The results suggest that prolonging the ACT more than 2 - 3 times normal is required to prevent activation of clotting during cardiopulmonary bypass.

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A comparative analysis of four activated clotting time measurement devices in cardiac surgery with cardiopulmonary bypass

Perfusion ◽

10.1177/0267659120949351 ◽

2020 ◽

pp. 026765912094935

Author(s):

Han Li ◽

Cyril Serrick ◽

Vivek Rao ◽

Paul M Yip

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

System Analysis ◽

Point Of Care ◽

Measurement Range ◽

Medical Decision ◽

Clotting Time ◽

Activated Clotting Time ◽

Decision Points ◽

Heparin Anticoagulation

Background: In cardiac surgery on cardiopulmonary bypass (CPB), heparin anticoagulation is monitored by point-of-care measurement of activated clotting time (ACT). The objective of this study was to compare four ACT systems in cardiac surgery in terms of their reproducibility, agreement and potential clinical impact at relevant medical decision points. Methods: The study included 40 cardiac surgery patients. Samples were taken at five time points before (T1), after heparinization for CPB (T2, T3, T4), and after heparin reversal (T5). The reproducibility, correlation, and differences in ACT values were assessed with two devices from each of the four ACT systems: Instrumentation Laboratory Hemochron Elite (Hmch), Medtronic HMS Plus (HMS), Abbott i-STAT, and Helena Abrazo. Subrange analyses were performed for low ACT values (results from T1, T5) and high ACT values (results from T2, T3, T4). Results: Within-system analysis showed strong linear correlation between paired measurements (R = 0.968-0.993). However, Hmch showed poorer reproducibility with highest proportion of values that exceed a difference of 10% and highest overall standard error of 74 seconds across the measurement range compared to that of the others (range 39-47 seconds, respectively). For inter-system comparison, using Hmch as reference, ACTs were strongly correlated as follows: HMS (R = 0.938), i-STAT (R = 0.911), and Abrazo (R = 0.911). Agreement analysis in the high ACT range showed HMS tended to have higher ACT values with +11% bias over Hmch, whereas i-STAT (–8% bias) and Abrazo (–13% bias) tended to underestimate. Post-protamine ACT results were dependent on device type where Hmch yielded highest post-protamine ACT (+13% higher than baseline) compared to –16% for HMS, –10% for iSTAT and 0% for Abrazo. Conclusions: Each device had individual reproducibility and biases, which may impact peri-operative heparin management. Careful validation must be undertaken when adopting a different method as decision limits would be affected. Clinicians should also be cautious using ACT as the only indicator for full heparin reversal.

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Application of goal-directed therapy for the use of concentrated antithrombin for heparin resistance during cardiac surgery

Perfusion ◽

10.1177/0267659120926089 ◽

2020 ◽

pp. 026765912092608

Author(s):

Alfred H Stammers ◽

Stephen G Francis ◽

Randi Miller ◽

Anthony Nostro ◽

Eric A Tesdahl ◽

...

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Heparin Therapy ◽

Sensitivity Index ◽

Transfusion Rate ◽

Clotting Time ◽

Activated Clotting Time ◽

Institutional Review ◽

Number Of Factors ◽

Heparin Resistance

The maintenance of anticoagulation in adult patients undergoing cardiopulmonary bypass is dependent upon a number of factors, including heparin concentration and adequate antithrombin activity. Inadequate anticoagulation increases the risk of thrombosis and jeopardizes both vascular and extracorporeal circuit integrity. The purpose of this study was to evaluate a goal-directed approach for the use of antithrombin in patients who were resistant to heparin. Following institutional review board approval, data were obtained from quality improvement records. A goal-directed protocol for antithrombin was established based upon heparin dosing (400 IU kg−1 body weight) and achieving an activated clotting time of ⩾500 seconds prior to cardiopulmonary bypass. Two groups of patients were identified as those receiving antithrombin and those not receiving antithrombin. Outcome measures included activated clotting time values and transfusion rates. Consecutive patients (n = 140) were included in the study with 10 (7.1%) in the antithrombin group. The average antithrombin dose was 1,029.0 ± 164.5 IU and all patients had restoration to the activated clotting time levels. Patients in the antithrombin group were on preoperative heparin therapy (80.0% vs. 24.6%, p = 0.001). Prior to cardiopulmonary bypass the activated clotting time values were lower in the antithrombin group (417.7 ± 56.1 seconds vs. 581.1 ± 169.8 seconds, p = 0.003). Antithrombin patients had a lower heparin sensitivity index (0.55 ± 0.17 vs. 1.05 ± 0.44 seconds heparin−1 IU kg−1, p = 0.001), received more total heparin (961.3 ± 158.5 IU kg−1 vs. 677.5 ± 199.0 IU kg−1, p = 0.001), more cardiopulmonary bypass heparin (22,500 ± 10,300 IU vs. 12,100 ± 13,200 IU, p = 0.016), and more protamine (5.4 ± 1.2 vs. 4.1 ± 1.1 mg kg−1, p = 0.003). The intraoperative transfusion rate was higher in the antithrombin group (70.0% vs. 35.4%, p = 0.035), but no differences were seen postoperatively. Utilization of a goal-directed algorithm for the administration of antithrombin for the treatment of heparin resistance is effective in patients undergoing cardiac surgery.

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