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• W2783757138 abstract "Despite more than a half century of “safe” cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence.To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications.Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Recommendations were written in the three following areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and to expand on the evidence base on the topic of anticoagulation therapy for CPB. Despite more than a half century of “safe” cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Recommendations were written in the three following areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and to expand on the evidence base on the topic of anticoagulation therapy for CPB. The Appendix and Supplemental Tables can be viewed in the online version of this article [https://doi.org/10.1016/j.athoracsur.2017.09.061] on http://www.annalsthoracicsurgery.org. The Appendix and Supplemental Tables can be viewed in the online version of this article [https://doi.org/10.1016/j.athoracsur.2017.09.061] on http://www.annalsthoracicsurgery.org. The development of cardiopulmonary bypass (CPB) in the 1960s so successfully enabled open heart surgery that rigorous evidence-based clinical trials did not play a part in the initial phases of development [1Stoney W.S. Evolution of cardiopulmonary bypass.Circulation. 2009; 119: 2844-2853Crossref PubMed Scopus (63) Google Scholar]. After World War II, clinicians were faced with more and more treatment choices, to the point that uncertainty existed about the “best” options. Indeed, Archie Cochrane recognized the need for a more rigorous approach to give clinicians answers to key questions about patient treatments. Cochrane’s efforts eventually led to the formation of the Cochrane Collaboration as a repository of evidence-based summaries to answer important clinical questions [2Ferraris V.A. Heroes and evidence.J Thorac Cardiovasc Surg. 2002; 124: 11-13Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar]. As a result, the modern era expects, and indeed requires, evidence to support surgeons’ interventions, preferably in the form of randomized controlled trials (RCTs). During the last 60-plus years since the introduction of clinical CPB as the foundation for performance of cardiac operations, surgeon investigators developed a safe, efficient, and reproducible method of performing highly complex cardiac procedures using CPB. Many advances in CPB are the result of evidence-based RCTs. Others derive from prospective cohort studies and still others, from anecdotal practice or consensus. Recognizing this large scope of practice and the varied nature of the evidence base to support the use of CPB, the Evidence Based Workforce of The Society of Thoracic Surgeons (STS) undertook a project to develop a series of practice guidelines that reflect the evidence base for the use of CPB in the current era. This effort included a collaboration with the Society of Cardiovascular Anesthesiologists (SCA) and the American Society of ExtraCorporeal Technology (AmSECT) to summarize available evidence in various areas of CPB. A critically important part of CPB is the use of anticoagulation therapy. To date, there are no evidence-based practice guidelines that define the optimal management of anticoagulation during the conduct of CPB. As a result, practice in this area is highly variable and not standardized in accordance with the evidence base to date. Therefore, the STS recognized this deficit and undertook a collaboration with the SCA and AmSECT to address the evidence gap regarding the use of anticoagulation treatment during CPB. This article reviews relevant published information about the use of anticoagulation for the conduct of CPB and provides a synthesis of the available evidence to create a clinical practice guideline. This guideline represents the initial evidence-based approach to the use of anticoagulation in CPB and is the only available comprehensive guideline of its kind. It is the hope of the authors that this guideline will stimulate investigators to amplify and elaborate on the evidence available on this topic. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms and were inclusive of the dates January 2000 to December 2015. The following terms comprised the standard baseline search terms for topics and were connected with the logical “OR” connector:•Extracorporeal circulation (MeSH number E04.292 includes extracorporeal membrane oxygenation, left heart bypass, hemofiltration, hemoperfusion, and cardiopulmonary bypass)•Cardiovascular surgical procedures (MeSH number E04.100 includes off-pump coronary artery bypass graft surgery, coronary artery bypass graft surgery, myocardial revascularization, all valve operations, and all other operations on the heart)•Pharmacologic actions of anticoagulant drugs (MeSH number D27.505 includes molecular mechanisms, physiologic effects, and therapeutic use of drugs)•Anticoagulation reversal (MeSH number D12.776 includes protamine sulfate and other protamines and nuclear proteins) These broad search terms allowed specific topics to be added to the search with the logical “AND” connector and publication types and groups to be excluded (Appendix). This search methodology provided a broad list of generated references specific for the search topic. The searches yielded 833 abstracts. Abstracts were reviewed by two independent reviewers for acceptance into the paper review stage. Abstracts with at least one acceptance were sent to full manuscript review. In all, 286 full papers were reviewed by at least two members of the writing group for inclusion eligibility in the guideline. To be included, a paper had to report data on both of the following: (1) anticoagulant used for cardiopulmonary bypass; and (2) the monitoring techniques used to measure that anticoagulation. After passing mandatory inclusion criteria, it was preferable that included papers have a prospective study design and also report on the frequency of anticoagulation monitoring, bleeding outcomes, and transfusion outcomes. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 that were referenced within a manuscript and considered to be sentinel papers were included to provide method, context, or additional supporting evidence for the recommendations. Individual members of the writing group read the retrieved references for their assigned topics and formulated recommendations based on assessment of the relevant literature. Only English language articles contributed to the final recommendations. For almost all topics reviewed, only evidence relating to adult patients entered into the final recommendations, primarily because of limited availability of high-quality evidence relating to pediatric patients having cardiac procedures. Evidence tables were constructed to ensure that selected studies conformed to minimum requirements in terms of study design and reporting of outcomes. (A representative evidence table evaluating the anticoagulation studies is shown in Supplemental Table 1; study appraisals of randomized controlled trials and meta-analyses are shown in Supplemental Table 2; and the Newcastle-Ottawa appraisal for nonrandomized studies is depicted in Supplemental Table 3). Members of the writing group wrote and developed recommendations based on review of the articles obtained using the search technique described above. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines (available at: http://www.americanheart.org/downloadable/heart/12604770597301209methodology_manual_for_acc_aha_writing_committees.pdf). The Appendix contains a summary of recommendations put forth in this guideline as a result of the evidence base. •A functional whole blood test of anticoagulation, in the form of a clotting time, should be measured and should demonstrate adequate anticoagulation before initiating and at regular intervals during CPB. (Level of Evidence C) •Bolus administration of unfractionated heparin based on weight is reasonable for achieving adequate anticoagulation, but individual response to heparin is heterogeneous and requires a therapeutic functional test of clot inhibition before initiation of CPB, independent of the bolus dose used. (Level of Evidence C)•It is reasonable to use activated clotting time (ACT) tests that produce “maximally activated” clotting times as these tests mitigate ACT variability, are less susceptible to hypothermia, and correlate more closely with factor Xa activity compared with tests that use a single activator. (Level of Evidence B)•It is reasonable to maintain activated clotting time above 480 seconds during CPB. However, this minimum threshold value is an approximation and may vary based on the bias of the instrument being used. For instruments using maximal activation of whole blood or microcuvette technology, values above 400 seconds are frequently considered therapeutic. (Level of Evidence C) •Use of a heparin dose-response formula may identify reduced sensitivity to heparin, but has not been shown to be more useful than weight-based heparin dosing in determining the heparin dose required to achieve an adequate ACT for initiation of CPB. (Level of Evidence B)•Use of heparin concentration monitoring in addition to ACT might be considered for the maintenance of CPB, as this strategy has been associated with a significant reduction in thrombin generation, fibrinolysis, and neutrophil activation. However, its effects on postoperative bleeding and blood transfusion are inconsistent. (Level of Evidence B)•During CPB, routine administration of unfractionated heparin at fixed intervals, with ACT monitoring, might be considered and offers a safe alternative to heparin concentration monitoring. (Level of Evidence C) Activated clotting time is considered the gold standard in monitoring anticoagulation for CPB. The establishment of a safe or optimal range for ACT dates back to data published in the 1970s when Bull and colleagues [3Bull B.S. Korpman R.A. Huse W.M. Briggs B.D. Heparin therapy during extracorporeal circulation. I. Problems inherent in existing heparin protocols.J Thorac Cardiovasc Surg. 1975; 69: 674-684Abstract Full Text PDF PubMed Google Scholar] showed no development of clot in the oxygenator or circuit when ACT was maintained above 300 seconds. However, Young and coauthors [4Young J.A. Kisker C.T. Doty D.B. Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer.Ann Thorac Surg. 1978; 26: 231-240Abstract Full Text PDF PubMed Scopus (184) Google Scholar] challenged this threshold when they demonstrated fibrin formation in the circuits of rhesus monkeys maintained on CPB with a minimum ACT value of 300 seconds, and they recommended that this threshold value be increased to 400 seconds by showing it was safe in 5 pediatric patients on CPB. To maintain a margin of safety above 400 seconds, the minimum acceptable ACT value of approximately 480 seconds became a “standard of care” that was used in numerous future studies and in clinical practice, but was based on limited evidence. Despite this widely accepted level of anticoagulation, there is no clear consensus on the accurate calculation of this initial dose of unfractionated heparin. Options for calculating the initial heparin bolus include a fixed, weight-based dose, (eg, 300 IU/kg), or use of point-of-care tests that measure the whole blood sensitivity to heparin using an associated dose response. In addition to the heterogeneity of heparin formulations themselves, individual responsiveness to heparin is variable. The pharmacodynamics of unfractionated heparin are highly dependent on the level and function of plasma antithrombin III. In patients with preoperative hypercoagulability or reduced antithrombin III responsiveness, increased levels of circulating heparin are necessary to achieve a therapeutic ACT value before CPB [5Na S. Stabilized infective endocarditis and altered heparin responsiveness during cardiopulmonary bypass.World J Surg. 2009; 33: 1862-1867Crossref PubMed Scopus (9) Google Scholar]. Na and coauthors [5Na S. Stabilized infective endocarditis and altered heparin responsiveness during cardiopulmonary bypass.World J Surg. 2009; 33: 1862-1867Crossref PubMed Scopus (9) Google Scholar] reported significant variations to heparin responsiveness in an observational study of patients with known, stabilized infectious endocarditis. Garvin and associates [6Garvin S. FitzGerald D.C. Despotis G. Shekar P. Body S.C. Heparin concentration-based anticoagulation for cardiac surgery fails to reliably predict heparin bolus dose requirements.Anesth Analg. 2010; 111: 849-855Crossref PubMed Scopus (0) Google Scholar] also reported observed variations in heparin response in patients having CPB. In a retrospective institutional database review of 3,880 patients, these investigators found wide variation in the heparin bolus dose required to obtain a target ACT. The initial unfractionated heparin bolus dose did not correlate well with the first post-heparin ACT (r2 = 0.03). The route and timing of the initial administration of unfractionated heparin has a direct impact on the ability to obtain a therapeutic ACT. A small randomized trial done by Grima and colleagues [7Grima C. The effects of intermittent prebypass heparin dosing in patients undergoing coronary artery bypass grafting.Perfusion. 2003; 18: 283-289Crossref PubMed Scopus (4) Google Scholar] found that intermittent doses of unfractionated heparin administered before CPB (100 IU/kg for 3 doses) maintained adequate levels of anticoagulation during CPB better than a single bolus dose of 300 IU/kg. Intermittent pre-CPB heparin treatment resulted in lower mean decreases in factor VIII, fibrinogen, antithrombin III, and platelet count than if a large bolus dose were administered. In a prospective nonrandomized trial performed by Neema and colleagues [8Neema P. Sinha P. Rathod R. Activated clotting time during cardiopulmonary bypass: is repetition necessary during open heart surgery?.Asian Cardiovasc Thorac Ann. 2004; 12: 47-52Crossref PubMed Scopus (6) Google Scholar], 6 of the 100 patients who received 300 IU/kg of unfractionated heparin before CPB had a resultant post-heparin ACT less than 350 seconds. Other pathologic disturbances such as thrombocytosis may limit the effectiveness of weight-based heparin bolus administration. Owing to the heterogeneity of the pharmacodynamic response to unfractionated heparin, the utilization of ex vivo heparin dose-response technologies was studied as a more accurate prediction of initial heparin dosing. Although ex vivo heparin dose-response technologies may identify patients who have a reduced sensitivity to conventional doses of heparin, these tests have limited ability to calculate correctly an optimal initial unfractionated heparin bolus dose. The observational study by Garvin and colleagues [6Garvin S. FitzGerald D.C. Despotis G. Shekar P. Body S.C. Heparin concentration-based anticoagulation for cardiac surgery fails to reliably predict heparin bolus dose requirements.Anesth Analg. 2010; 111: 849-855Crossref PubMed Scopus (0) Google Scholar] demonstrated poor correlation of the calculated in vitro heparin dose response curve compared with the actual patient heparin dose response, resulting in a failure to reach therapeutic ACT values in nearly 17% of patients. During CPB, an overestimation of heparin concentration may occur when using the ACT assay alone. Falsely elevated ACT values may be observed under conditions of hypothermia, reduced hemoglobin concentration, hypofibrinogenemia, and pharmacologic agents that are not associated with a concomitant increase in heparin concentration [9Shore-Lesserson L. Evidence based coagulation monitors: heparin monitoring, thromboelastography, and platelet function.Semin Cardiothorac Vasc Anesth. 2005; 9: 41-52Crossref PubMed Scopus (46) Google Scholar]. In a controlled, nonrandomized study of 42 patients, Machin and colleagues [10Machin D. Devine P. The effect of temperature and aprotinin during cardiopulmonary bypass on three different methods of activated clotting time measurement.J Extra Corpor Technol. 2005; 37: 265-271PubMed Google Scholar] demonstrated prolongation of ACT values during hypothermic CPB when compared with normothermic CPB. Leyvi and colleagues [11Leyvi G. Shore-Lesserson L. Harrington D. Vela-Cantos F. Hossain S. An investigation of a new activated clotting time MAX-ACT in patients undergoing extracorporeal circulation.Anesth Analg. 2001; 92: 578-583Crossref PubMed Google Scholar] reported similar ACT prolongation under conditions of both hypothermia and hemodilution using a number of ACT technologies while plasma antifactor Xa heparin level activity remained constant. Maintaining ACT values during CPB without heparin concentration monitoring may result in lower doses of heparin. These known sensitivity limitations in ACT monitoring may result in subclinical plasma coagulation occurring during CPB. Whole blood heparin concentration assays are statistically more closely correlated with plasma anti-Xa levels than the ACT [12Koster A. Fischer T. Praus M. et al.Hemostatic activation and inflammatory response during cardiopulmonary bypass: impact of heparin management.Anesthesiology. 2002; 97: 837-841Crossref PubMed Scopus (128) Google Scholar]. Clinically, heparin concentration tests are performed alongside a functional test of clotting, such as an ACT, because a therapeutic functional confirmation of anticoagulation provides important safety data. In a randomized controlled trial of 200 patients, Koster and colleagues [13Despotis G.J. Joist J.H. Hogue C.W. et al.The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective, randomized evaluation in patients undergoing cardiac operation.J Thorac Cardiovasc Surg. 1995; 110: 46-54Abstract Full Text PDF PubMed Scopus (214) Google Scholar] found that adhering to a heparin concentration maintenance protocol led to a significant reduction in thrombin generation, fibrinolysis, and neutrophil activation, when compared with ACT monitoring alone (480 seconds). Despotis and associates [14Despotis G.J. Joist J.H. Hogue C.W. et al.More effective suppression of hemostatic system activation in patients undergoing cardiac surgery by heparin dosing based on heparin blood concentrations rather than ACT.Thromb Haemost. 1996; 76: 902-908Crossref PubMed Google Scholar] randomized patients to ACT-based (using 5,000 units unfractionated heparin doses to maintain ACT values >480 seconds) versus heparin concentration-based management (with minimum ACT >480 seconds), and reported a higher heparin total dose in patients in the heparin concentration group (612 ± 147 U/kg versus 462 ± 114 U/kg, p < 0.0001). Patients in the heparin concentration group also had lower protamine to heparin ratios and required significantly fewer blood product transfusions (platelets, plasma, and cryoprecipitate) than the ACT-based control group. Another randomized trial of 31 patients scheduled for reoperation resulted in significant reductions in perioperative blood loss and blood product usage when maintaining higher patient-specific heparin dosing during CPB [15Pappalardo F. Franco A. Crescenzi G. De Simone F. Torracca L. Zangrillo A. Anticoagulation management in patients undergoing open heart surgery by activated clotting time and whole blood heparin concentration.Perfusion. 2006; 21: 285-290Crossref PubMed Scopus (12) Google Scholar]. Another study found reduced platelet activation and evidence of reduced thrombin generation with heparin concentration monitoring compared with routine ACT monitoring [16Hofmann B. Bushnaq H. Kraus F.B. et al.Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy.Perfusion. 2013; 28: 412-418Crossref PubMed Scopus (19) Google Scholar]. Together, these studies suggest that whole blood heparin concentration monitoring results in larger doses of unfractionated heparin during CPB and improved hemostatic suppression compared with ACT monitoring alone. However, these results did not translate into improved clinical outcomes and have not been wholly reproducible in the literature. A retrospective analysis involving 686 patients favored ACT-based monitoring compared with heparin concentration monitoring because of less postoperative bleeding and transfusion requirements associated with ACT-based monitoring [17Newsome J. Stipanovich K. Flaherty S. Comparison of heparin administration using the Rapidpoint Coag and Hepcon HMS.J Extra Corpor Technol. 2004; 36: 139-144PubMed Google Scholar]. Traditionally, the gold standard for measuring the anticoagulant effects of heparin is inhibition of factor Xa (anti-Xa) activity. Factor Xa is a major target for unfractionated heparin and can be readily measured in plasma using laboratory assays. The various studies that seek to validate a new measure of heparin activity, or a clotting time assay, use anti-Xa activity as the gold standard comparison. However, plasma assays for anti-Xa activity are not ideally suited for point-of-care testing. Anti-Xa measurement serves as a validating test for novel point-of-care assays that reflect anti-Xa activity. Hansen and associates [18Hansen R. Koster A. Kukucka M. Mertzlufft F. Kuppe H. A quick anti-Xa-activity-based whole blood coagulation assay for monitoring unfractionated heparin during cardiopulmonary bypass: a pilot investigation.Anesth Analg. 2000; 91: 533-538Crossref PubMed Scopus (12) Google Scholar] studied a whole blood modified ACT test and found it to be highly correlated to laboratory anti-Xa measurement. Helstern and associates [19Hellstern P. Bach J. Simon M. Saggau W. Heparin monitoring during cardiopulmonary bypass surgery using the one-step point-of-care whole blood anti-factor-Xa clotting assay Heptest-POC-Hi.J Extra Corpor Technol. 2007; 39: 81-86PubMed Google Scholar] reported another one-step clotting assay that correlates well with anti-Xa tests and is not influenced by hemodilution, but clinical studies are lacking. Routine redosing of unfractionated heparin at fixed intervals during CPB, despite a therapeutic ACT, is commonly used when heparin concentration assays are not available to simulate the practice of “higher heparin dosing.” This practice prescribes additional fixed doses of unfractionated heparin at specific timepoints, even though ACT may be above target. In a prospective trial of 100 patients presenting for cardiac surgery, one third of the initial heparin bolus was administered at the 90-minute point of CPB, with repeat doses every 60 minutes thereafter [8Neema P. Sinha P. Rathod R. Activated clotting time during cardiopulmonary bypass: is repetition necessary during open heart surgery?.Asian Cardiovasc Thorac Ann. 2004; 12: 47-52Crossref PubMed Scopus (6) Google Scholar]. This strategy maintained adequate anticoagulation during the entire period of hypothermic CPB; bleeding variables were not reported. Despite the reported benefits of higher heparin dosing, other studies seemingly contradict these results. In a small prospective trial of 21 patients, Gravlee and colleagues [20Gravlee G.P. Haddon W.S. Rothberger H.K. et al.Heparin dosing and monitoring for cardiopulmonary bypass. A comparison of techniques with measurement of subclinical plasma coagulation.J Thorac Cardiovasc Surg. 1990; 99: 518-527Abstract Full Text PDF PubMed Google Scholar] concluded that subclinical plasma coagulation occurs during CPB despite heparin concentrations greater than 4.1 IU/mL. Furthermore, postoperative mediastinal chest tube drainage correlates with increased heparin concentration, especially if heparin rebound is not carefully monitored. A subsequent, prospective study of 63 patients by Gravlee and colleagues [21Gravlee G.P. Rogers A.T. Dudas L.M. et al.Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding.Anesthesiology. 1992; 76: 393-401Crossref PubMed Scopus (70) Google Scholar] showed that subjects who received an unfractionated heparin bolus of 400 IU/kg and had heparin concentration maintained greater than 4 IU/mL did not differ in mediastinal drainage or transfusion products from a control group of patients receiving a bolus dose of 200 IU/kg plus additional heparin for ACT values less than 400 seconds. A prospective trial in 31 patients undergoing cardiac surgery revealed that all patients had a residual circulating heparin level after protamine administration (mean 0.18 IU/mL), detected by a chromogenic anti-Xa assay. This residual" @default.
• W2783757138 created "2018-01-26" @default.
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• W2783757138 date "2018-02-01" @default.
• W2783757138 modified "2023-10-11" @default.
• W2783757138 title "The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines ∗ —Anticoagulation During Cardiopulmonary Bypass" @default.
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