Anticoagulation For Cardiopulmonary Bypass Research Articles

Comparison of Blood Concentration and Weight-Based Heparin and Protamine Dosing Strategies for Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weightwhich fails to account for the heterogeneous response to heparinin each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes. We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparinand/or protamine based on measured heparin concentration versus patient'stotal body weightfor CPB.Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding. Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included.Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression. There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducingbleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss.The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate.With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.

Bivalirudin anticoagulation for cardiopulmonary bypass during cardiac surgery.

Heparin is the primary anticoagulant for cardiopulmonary bypass (CPB) support during cardiac surgery. While widely used, ∼2% of cardiac surgery patients develop heparin-induced thrombocytopenia (HIT) and 4-26% develop heparin resistance. Bivalirudin is an alternative anticoagulant mainly used for percutaneous coronary interventions. Given the challenges associated with heparin anticoagulation, we conducted a review to explore the use of bivalirudin for CPB surgery. PubMed and Embase scoping review included 2 randomized controlled trials, a retrospective comparison study, 3 pilot studies, and 30 case reports. To provide a contemporary series, we searched for articles published from 2010 to 2023. Our review included studies from both adult and pediatric populations. While data is limited, bivalirudin seems to supply similar effectiveness and safety as heparin for CPB anticoagulation. Across the three comparative studies, the heparin cohorts had a 0-9% mortality rate and 0-27% rate of major bleeding/reoperation compared to a 0-3% mortality and 0-6% major bleeding/reoperation rate for the bivalirudin cohorts. Bivalirudin was successfully used as an anticoagulant in a wide range of CPB surgeries (e.g., heart transplants, ventricular assisted device placements, and valve repairs). Successful patient outcomes were reported with bivalirudin infusion of ∼2mg/kg/hour, activated clotting time monitoring (target >400s or 2.5× baseline), use of cardiotomy suctions, minimization of stagnant blood, and post-bypass modified ultrafiltration. Bivalirudin is a safe and effective anticoagulant for CPB, especially for patients with HIT or heparin resistance. Further comparative research is called for to optimize bivalirudin utilization for CPB during cardiac surgery.

Intravenous Dabigatran Provides Adequate Anticoagulation for Cardiopulmonary Bypass Using a Rabbit Model.

Heparin anticoagulation has been used successfully for cardiopulmonary bypass (CPB). However, an alternative anticoagulant approach is desirable due to the cases of heparin-induced thrombocytopenia. Dabigatran provides anticoagulation for an in vitro model of simulated CPB. The current analysis tests the hypothesis that dabigatran provides sufficient anticoagulation for CPB in intact rabbits. Nonlinear mixed effects models were used to estimate dabigatran parameters for a two-compartment pharmacokinetic model in 10 New Zealand White rabbits. A dabigatran infusion designed to maintain a plasma concentration of 90 µg/ml was run throughout CPB based on the pharmacokinetics. Animals were subjected to sternotomy and anticoagulated with IV dabigatran (six animals) or heparin (four animals). Rabbits were cannulated centrally using the right atrium and ascending aorta and CPB was maintained for 120 min. Measurement of activated clotting time, thromboelastometric reaction time, and blood gases were performed during CPB. Then, the animals were euthanized, and the brain and one kidney were removed for histology. Sections of the arterial filters were inspected using electron microscopy. The observed dabigatran concentrations during CPB were greater than the target concentration, ranging from 137 ± 40 μg/ml at 5 min of CPB to 428 ± 150 μg/ml at 60 min, and 295 ± 35 μg/ml at 120 min. All rabbits completed 2 h of CPB without visible thrombosis. In the two groups, reaction time values were elevated, reaching 10,262 ± 4,198 s (dabigatran group) and 354 ± 141 s (heparin group) at 120 min of CPB. Brains and kidneys showed no evidence of thrombosis or ultrastructural damage. Sections of the arterial line filter showed minimal or no fibrin. There was no significant difference in outcomes between dabigatran- and heparin-treated animals. In this first-use, proof-of-concept study, the authors have shown that dabigatran provides acceptable anticoagulation similar to heparin to prevent thrombosis using a rabbit CPB model.

Management of perioperative anticoagulation in a patient with antiphospholipid antibody syndrome undergoing cardiac surgery: A case report

Patients with Antiphospholipid syndrome (APLS) are at high risk for both bleeding and thrombotic complications during cardiac surgery involving cardiopulmonary bypass (CPB). In this case we present a patient with APLS and Immune Thrombocytopenic Purpura who successfully underwent aortic valve replacement (AVR) with CPB despite recent craniotomy for subdural hematoma evacuation. Anticoagulation for CPB was monitored by targeting an Activated Clotting Time (ACT) that was 2× the upper limit of normal. A multidisciplinary approach was essential in ensuring a safe and successful operation.

Alternatives to heparin anticoagulation for cardiopulmonary bypass and extracorporeal membrane oxygenation

Cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) are both mechanical circulatory support technologies that augment the native heart and/or lung function. They involve drainage and reinfusion of blood while performing extracorporeal gas exchange. 1 In both devices, contact between patient blood and the non-endothelialized surface of the circuit triggers an inflammatory response and pro-coagulation cascade. 2–5 As a result, prophylactic anticoagulation is integral to prevent catastrophic thrombosis of the circuitry. In rare instances, there exist contraindications to heparin use, necessitating alternative management strategies. 6 In this review, we will examine heparin contraindications in mechanical circulatory support and summarize alternative approaches to anticoagulation in these circumstances.

Correlation between activated clotting time and anti-xa activity in patients undergoing cardiac surgery requiring cardiopulmonary bypass

Introduction Anticoagulation for cardiopulmonary bypass (CPB) has historically involved the use of heparin as the anticoagulant of choice. Activated clotting time (ACT) is considered the gold standard for determining adequate level of anticoagulation before and during CPB. Recent guidelines suggest ACT > 480 seconds during CPB; however, initial validation studies were done on much older generations of bypass circuits in animal models and results have not been replicated in more recent clinical studies. ACT is also a measure of whole blood clotting and does not necessarily reflect degree of heparin activity. Newer studies have shown poor correlation between ACT and anti-Xa activity levels, the latter considered the gold standard for monitoring heparin activity. We sought to quantify the correlation between two point-of-care ACT instruments with the laboratory based anti-Xa activity assay for patients undergoing cardiac surgery requiring CPB at various time points during surgery. Methods 50 patients undergoing cardiac surgery requiring CPB were consented and enrolled. Blood samples were taken from each patient to examine the correlation between two ACT point-of-care instruments, Hemochron and i-STAT, and that of anti-Xa activity at various points during surgery. These timepoints were at baseline, after initial heparin bolus prior to initiating bypass, during CPB, and after protamine reversal of heparin. Pearson's correlation coefficient (r) was calculated for each set of comparisons. Results We obtained a total of 542 comparisons between ACT values and anti-Xa activity. There was poor correlation between both ACT instruments and anti-Xa activity after the initial bolus of heparin prior to bypass (r = 0.27 and 0.15), with correlations worsening on bypass (r = 0.11 and 0.04). i-STAT generally correlated better with anti-Xa activity and the two ACT instruments generally correlated well with each other (r = 0.88, all timepoints), except while on CPB (r = 0.11, CPB only). There was greater than 16-fold difference seen in heparin activity between patient samples when ACT > 400, with anti-Xa activity ranging from 0.78 to 16.10 U/mL. The average ACT (i-STAT) after protamine reversal was 22 seconds lower than baseline; however, average post-protamine anti-Xa activity was 0.77 U/mL. Discussion Our results suggest perhaps excessive and/or suboptimal anticoagulation in some patients during CPB and inadequate reversal of heparin post-bypass despite ACT values normalizing. Using ACT alone as a point-of-care tool may be inadequate in determining the optimal level of anticoagulation during bypass and reversal of heparin in patients undergoing cardiac surgery requiring CPB.

Preoperative Implementation of Transverse Thoracic Muscle Plane Block and Rectus Sheath Block Combination for Pediatric Cardiac Surgery

Systemic intravenous administration of opioids is the main treatment strategy for intraoperative and postoperative pain management in patients undergoing cardiac surgery with sternotomy. However, using lower doses of opioids may achieve the well-established benefits of the fast-track approach, with minimal opioid-related side effects. Postoperative pain is coupled with a long stay in the intensive care unit. Although neuraxial anesthesia has some benefits, its use remains controversial due to the potential development of epidural hematoma after anticoagulation for cardiopulmonary bypass and coagulopathy after cardiac surgery. Therefore, there is a need for other effective postoperative analgesic strategies, such as peripheral nerve blocks other than neuraxial anesthesia, for cardiac surgery with sternotomy. The effects of real-time ultrasound-guided transverse thoracic muscle plane (TTP) block on postoperative pain after sternotomy have been reported; however, the pain and discomfort in the epigastric area caused by chest drainage tubes placed through the rectus abdominis muscle also are major postoperative problems after cardiac surgery. Herein, the authors report on a preoperative combination of TTP block and rectus sheath block (RSB) for postoperative pain management after cardiac surgery with sternotomy that addresses pain in both the chest and epigastric areas. Considering previous studies, it is presumed that preemptive analgesic effects can be expected via a combination of the TTP block and RSB, and indeed, the preemptive effect was observed in the present study's patients. In this article, the procedure and tips for combining the TTP block and RSB are introduced.

Evaluation of Point-of-Care ACT Coagulometers and Anti-Xa Activity During Cardiopulmonary Bypass

Objective: The activated clotting time (ACT) is used worldwide to confirm safe heparin anticoagulation for cardiopulmonary bypass. For the present study, the performances of 2 commonly used ACT devices were compared with each other and with anti-Xa levels throughout the surgical procedure in order to understand whether they can be used interchangeably.Design: Prospective study.Setting: Tertiary care center.Participants: The study comprised 33 elective adult cardiac surgical patients.Interventions: Blood samples were taken at standard times throughout the surgery (after induction, after heparin bolus, 4 samples at 30-minute intervals during cardiopulmonary bypass, after protamine), and ACTs and anti-Xa levels were analyzed. Data were compared using receiver operating characteristics and LOESS regression.Measurements and Main Results: The correlation between anti-Xa levels and the Hemochron ACT (Instrumentation Laboratory, Bedford, MA) was acceptable (r = 0.82, 95% confidence interval [CI] 0.757-0.868; p < 0.0001), as was the correlation between anti-Xa levels and the i-STAT (Abbott Point of Care, Abbott Park, IL) (r = 0.81, 95% CI 0.738-0.858; p < 0.0001). The correlation between the 2 ACT methods was poorer (r = 0.77, 95% CI 0.707-0.828; p < 0.0001) than their correlation to anti-Xa levels. When compared with anti-Xa levels, the sensitivity and specificity were mediocre for both devices, although the i-STAT performed better than the Hemochron ACT. The Hemochron ACT read higher values than the i-STAT ACT throughout the course of the surgery.Conclusion: The correlation between the Hemochron ACT and i-STAT ACT is moderate, and they have different sensitivity and specificity when compared with anti-Xa levels. This suggests that ACT devices should not be used interchangeably, but cut-off values for safe anticoagulation during cardiopulmonary bypass should be determined for each type of device, particularly when switching supplier.

Aptamers as Rapid Onset and Rapidly Reversible Antithrombotic Agents

Clinical evaluation of our factor IXa RNA aptamer in two thousand patients undergoing percutaneous coronary intervention has demonstrated that aptamers can rapidly and potently inhibit their target proteins in patients and that antidote molecules can rapidly and precisely control such activity in the minute time frame. These observations suggest that aptamers represent useful molecules to tightly control biochemical processes in humans in real time. To begin to explore this potential further, we have started to evaluate the utility of antidote-mediated control of aptamers for a variety of other therapeutic and diagnostic applications. We will describe our recent progress developing a rapidly controllable factor Xa anticoagulant aptamer to effectively yet reversibly control blood coagulation during cardiopulmonary bypass surgery and a rapidly reversible VWF aptamer for improving the treatment of thrombotic stroke. We have observed that aptamers, which target exosites on coagulation factors, can complement active site inhibitors to yield potent anticoagulant regiments (Gunaratne et al., 2018) that can support circulation of blood through extracorporeal oxygenator circuits. Moreover we have observed that an aptamer targeting the A1 domain of VWF can serve as a rapid onset and rapidly reversible antithrombotic agent. This aptamer prevents platelet recruitment and can induce recanalization of occluded arteries while a matched antidote oligonucleotide can rapidly reverse such anti-platelet activity and thereby limit bleeding following vascular injury (Nimjee et al., 2019). Collectively these clinical and preclinical studies lead us to believe that rapidly controllable aptamers represent valuable therapeutic agents that will provide physicians the ability to monitor and precisely control blood coagulation, as well as other biological pathways, in real time in response to individual patients' needs. GunaratneR, KumarS, FrederiksenJW, et al. Multimodal, antidote-controllable anticoagulation for cardiopulmonary bypass using aptamer-drug pairs. Nature Biotechnology 2018;36:606-613. NimjeeSM, Dornbos, IIID, Pitoc GA, et al. Preclinical Development of a VWF Aptamer to Limit Thrombosis and Engender Arterial Recanalization of Occluded Vessels. Molecular Therapy. 2019;27:1228-1241. Disclosures Sullenger: Basking Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents &amp; Royalties.

A case of heparin resistance or a case of inadequacy of anticoagulation monitoring?

Introduction Despite during cardiopulmonary bypass (CPB) inhibiting coagulation is essential, the clinical management of heparin based anticoagulation is still not standardized. Heparin resistance (HR) is a reported feature (10-20%), but there is not a unique definition universally accepted. Methods An 80 years old woman was listed for elective CABG and aortic valve replacement. She had no recognized risk-factors for HR; her pre-op laboratory tests (platelet count, coagulation, liver function) were within normal range. After induction of general anesthesia the baseline ACT was 137sec. 20000IU bolus of unfractionated heparin (300IU/kg) was administered and ACT reached 250sec. Other 10000IU bolus of heparin and 1000IU of AT-III were administered, but ACT remained inadequate (254sec). A ROTEM test showed prolonged INTEM-CT and normal HEPTEM-CT; laboratory tests revealed aPTT >220sec and plasmatic heparin >3IU/mL. According to these results, CPB was started. During CPB anticoagulation was monitored with both ACT and laboratory tests: ACT has never been concordant with aPTT neither ACT increased after further 5000IU bolus of heparin. At the end of CPB, heparin was neutralized with protamine 350mg and tranexamic-acid 2g was administered: the final ACT was 143sec. Nevertheless, the patient was still bleeding and she needed RBC transfusion: a second ROTEM test showed very prolonged INTEM-CT and HEPTEM-CT and normal FIBTEM parameters, thus the patient was efficaciously treated with prothrombin-complex concentrate. Later, in ICU the first laboratory tests revealed normal aPTT and plasmatic heparin below the sensibility range; a third ROTEM test ran totally normal. Results According to common definitions of HR (failure to reach therapeutic ACT despite high doses of heparin), this case should identify an HR situation. However, both ROTEM and laboratory tests (aPTT, plasmatic heparin) confirmed the patient was properly anticoagulated. Conversely, after protamine administration ACT indicated the return to a normal coagulation state, while clinical evidence, aPTT and ROTEM test showed the contrary. These discordant results may be due to the different activators used in ROTEM-INTEM, aPTT and ACT (respectively ellagic-acid, kaolin and celite). Discussion A new unanimous definition for HR is needed to develop a standardized management. ACT is useful to monitor bedside anticoagulation, but second-line tests should always be available and adopted to characterize doubtful cases and verify HR.

Epoprostenol Therapy for a Pediatric Patient With Subacute Heparin-Induced Thrombocytopenia and a Ventricular Assist Device Undergoing Heart Transplant: A Case Report

Concerns remain regarding the use of direct thrombin inhibitors for cardiopulmonary bypass anticoagulation in pediatric patients with heparin-induced thrombocytopenia undergoing complex cardiac surgery. We describe the safe and effective use of epoprostenol sodium as an alternative therapy before heparin exposure for a pediatric patient with subacute heparin-induced thrombocytopenia and a ventricular assist device undergoing heart transplant.

Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors. We demonstrate that combinations of 11F7t and catalytic-site FXa inhibitors enhance anticoagulation in purified reaction mixtures and plasma. Aptamer-drug combinations prevented clot formation as effectively as UFH in human blood circulated in an extracorporeal oxygenator circuit that mimicked CPB, while avoiding side effects of UFH. An antidote could promptly neutralize the anticoagulant effects of both FXa inhibitors. Our results suggest that drugs and aptamers with shared targets can be combined to exert more specific and potent effects than either agent alone.

The use of cangrelor with heparin for left ventricular assist device implantation in a patient with acute heparin-induced thrombocytopenia

BackgroundOptimal anticoagulation strategy for cardiopulmonary bypass (CPB) in end-stage heart failure patients with heparin-induced thrombocytopenia (HIT) requiring left ventricular assist device (LVAD) implantation remains uncertain. Presently, there are no large-scale randomized studies comparing outcomes of alternative anticoagulation strategies for CPB in this patient population. A novel antiplatelet agent – cangrelor, which is a potent P2Y12 inhibitor with robust antiplatelet efficacy, rapid reversibility, and measurable drug effect, has become available since 2015. Intraoperative anticoagulation for CPB using cangrelor with heparin has not been reported before.Case presentationWe report the case of a 47-year-old male with ischemic cardiomyopathy and acute HIT, who underwent an urgent LVAD implantation using cangrelor with heparin for anticoagulation on CPB. This novel strategy resulted in satisfactory anticoagulation for CPB without perioperative thromboembolic events or major bleeding requiring reoperation.ConclusionsCangrelor with heparin was an effective anticoagulation strategy for CPB in this critically ill patient with acute HIT requiring an urgent LVAD implantation. Further studies are warranted to evaluate its efficacy and replicability in other patients with acute or subacute HIT who require urgent cardiac surgery.

Assessing the Benefits of Preoperative Thoracic Epidural Placement for Lung Transplantation

The authors investigated the effect of preoperative thoracic epidural (PreTE) catheter placement versus not placing a preoperative thoracic epidural catheter (NoPreTE) on the duration of postoperative ventilation time, time to become coherent (measured as time to become Confusion Assessment Method-intensive care unit [ICU] negative), opioid consumption, ICU length of stay (LOS), and hospital LOS. Retrospective cohort design. Single institution, university hospital. Patients undergoing lung transplantation. PreTE group was defined as patients who received a thoracic epidural preoperatively. NoPreTE group was defined as patients who either received a thoracic epidural postoperatively or who did not receive a thoracic epidural postoperatively. Fifty-six patients for the PreTE and 99 for NoPreTE groups were included in the study. After a excluding patients with postoperative ventilation times greater than 96 hours, preoperative thoracic epidural was associated with shorter time on the ventilator (19.1 hours v 30.6 hours; p < 0.001), time to become coherent (26.4 hours v 37.6 hours; p = 0.008), ICU LOS (6.4 days v 12.4 days; p = 0.018), and hospital LOS (15.9 days v 23.5 days; p = 0.04) compared to patients who did not receive a preoperative epidural. After controlling for single versus double lung transplantation and duration of cardiopulmonary bypass (CPB), differences in time to become coherent, ICU LOS, and hospital LOS became nonsignificant. Opioid consumption was significantly higher in those patients who did not receive a preoperative epidural. Despite a high rate of anticoagulation for CPB (89.5%), no neurologic complications or epidural hematomas were observed. For those lung transplant patients ventilated for less than 96 hours postoperatively, preoperative thoracic epidural placement is associated with shorter postoperative ventilator time and reduced opioid consumption. Time to become coherent postoperatively, ICU LOS, and hospital LOS also improved in this cohort, though the significance decreased after adjusting for possible confounders. A larger prospective study is necessary to confirm if timing of thoracic epidural placement alters time to become coherent postoperatively and ICU LOS.

STS/SCA/AmSECT Clinical Practice Guidelines: Anticoagulation during Cardiopulmonary Bypass

Despite more than a half century of “safe” cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation 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 (STS), the Society of Cardiovascular Anesthesiologists (SCA), and the American Society of Extracorporeal Technology (AmSECT) developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered together 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 for CPB using the available evidence. To identify relevant evidence a systematic review was outlined and literature searches were conducted in PubMed® using standardized 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 prior to 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 AHA/ACCF 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, 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 expand upon the evidence base on the topic of anticoagulation for CPB.

Bivalirudin Anticoagulation for a Pediatric Patient with Heparin-Induced Thrombocytopenia and Thrombosis Requiring Cardiopulmonary Bypass for Ventricular Assist Device Placement

The direct thrombin inhibitor bivalirudin is an option for anticoagulation in patients with heparin induced thrombocytopenia (HIT) requiring cardiopulmonary bypass (CPB). There are a limited number of reports of pediatric patients in which bivalirudin has been used for anticoagulation for CPB. We present the case of an 11 year old male with acute onset heart failure secondary to idiopathic dilated cardiomyopathy that developed heparin induced thrombocytopenia with thrombosis (HITT). The patient was anticoagulated in the operating room with bivalirudin and placed on CPB for insertion of a HeartWare® Ventricular Assist Device (Heartware®). Modified techniques were utilized. This included use of the Terumo CDI 500 (Terumo Cardiovascular Systems, Inc.) in-line blood gas monitor which contains a heparin coated arterial shunt sensor. We flushed this sensor with buffered saline preoperatively and noted no significant decrease in platelet count postoperatively. The patient was successfully placed on the ventricular assist device and was subsequently listed for heart transplantation.

Anemia Is a Risk Factor of New Intraoperative Hemorrhagic Stroke During Valve Surgery for Endocarditis

Infective endocarditis is often associated with cerebral complications, the most serious of which is intraoperative hemorrhagic stroke owing to anticoagulation for cardiopulmonary bypass. However, its prevalence and risk factors are unknown. We evaluated the prevalence and risk factors of intraoperative hemorrhagic stroke in patients with infective endocarditis. In 246 patients who underwent valve surgery for active endocarditis between 2005 and 2012, 127 patients had both preoperative and postoperative intracranial neuroimaging. The prevalence and risk factors of intraoperative stroke were analyzed in those 127 patients. Valve surgery was performed in 127 patients 19.6 ± 27.1 days after infective endocarditis diagnosis. Fourteen experienced intraoperative hemorrhagic stroke, and 1 died. None of 29 patients with preoperative hemorrhagic stroke showed exacerbation of hemorrhagic lesions, whereas 1 of 57 patients with preoperative cerebral infarction showed hemorrhagic transformation of infarct lesions. Thirteen of 14 hemorrhagic complications were new ectopic intracranial hemorrhage. Multivariate analysis showed not preoperative cerebral lesions but preoperative low hemoglobin level as the only risk factor for intraoperative hemorrhagic stroke (odds ratio, 0.51; 95% confidence interval, 0.26 to 0.87; p = 0.03). A preoperative hemoglobin cutoff value of 9.2 g/dL was determined by receiver operating curve analysis. Of 41 patients with preoperative hemoglobin level less than 9.2 g/dL, 9 (22%) had intraoperative new hemorrhage, whereas 4 (5%) of 86 patients with hemoglobin level of at least 9.2 g/dL had ectopic new hemorrhage. Intraoperative hemorrhagic stroke was not rare, and ectopic hemorrhagic stroke, associated with preoperative anemia, was more prevalent than hemorrhagic transformation of existing cerebral lesions.

Alternatives to heparin and protamine anticoagulation for cardiopulmonary bypass in cardiac surgery

Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB) cardiac procedures, but this strategy has some limitations. The primary objective of this study was to determine the reliable alternatives for anticoagulation during CPB for cardiac surgery. For each drug proposed, the secondary objectives were to outline the main advantages and disadvantages, to propose a therapeutic protocol, and to provide a cost-benefit analysis. A systematic review of the literature was performed between September 2012 and December 2013. It was based on the protocol established by the "Cochrane collaboration Handbook". Twenty articles were analyzed. The Thériaque database from the University Hospital of Grenoble made the economic analysis possible. Seven alternative anticoagulation strategies were considered: danaparoid sodium, lepirudin, argatroban, bivalirudin, ancrod, idraparinux, and EP217609. Danaparoid sodium has issues with individual variability. Several studies (EVOLUTION-ON, CHOOSE-ON) proposed a reliable therapeutic protocol for bivalirudin. Ancrod resulted in an increase in the transfusion of blood products. Direct thrombin inhibitors offer a promising alternative. EP217609 is a synthetic anticoagulant currently undergoing Phase IIa clinical trials. It is an indirect inhibitor of factor Xa, a direct inhibitor of free and bound thrombin, and can be neutralized by avidin. The ideal anticoagulation strategy for cardiac surgery with CPB does not exist. Heparin and protamine remain the gold standard for anticoagulation therapy. To date, bivalirudin is the most promising molecule despite its high cost and lack of a readily available antagonist.

Cardiopulmonary bypass strategy with low-dose heparin and nafamostat mesilate in cardiac surgery: A safe option for patients with acute stroke

From the Narayana Hrudayalaya Institute of Medical Sciences, Bangalore, India; and theDepartment ofCardiology, St. John’sMedicalCollegeHospital,Bangalore, India. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Dec 13, 2011; revisions received March 2, 2012; accepted for publication March 16, 2012; available ahead of print April 27, 2012. Address for reprints: Naoto Morimoto, MD, PhD, Department of Cardiovascular Surgery, Himeji Cardiovascular Center, 520, Saishoko, Himeji, Hyogo, 670-0981, Japan (E-mail: naotofrcs@gmail.com). J Thorac Cardiovasc Surg 2012;144:726-8 0022-5223/$36.00 Copyright 2012 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2012.03.030

Spontaneous Ear Hemorrhage During Cardiac Surgery

A 79-year-old patient who underwent mitral valve replacement experienced prolonged elevated central venous pressure associated with poor venous return during a cardiopulmonary bypass. After the procedure, the patient was noted to have spontaneous bleeding from the left ear. Otolaryngologic examination in the operating room showed no trauma in the exterior auditory canal and suggested that the hemorrhage was related to a superior vena cava syndrome and anticoagulation during the cardiopulmonary bypass. Determinants and management considerations of poor venous return, including maintenance of cerebral perfusion pressure, are discussed.